{ "name": "H2Medicine", "language": "en", "url": "https://h2medicine.org", "other_language_url": "https://h2medizin.org", "description": "Scientific evidence overview of molecular hydrogen (H₂) in humans — not medical advice. Null and negative results are included.", "count": 731, "studies": [ { "pmid": "42050215", "year": 2026, "title": "The essential role of hydrogen gas recycling by gut microbes in reducing deuterium load in host mitochondria: is trimethylamine oxide a deuterium sensor?", "title_en": null, "title_de": "Die wesentliche Rolle des Wasserstoffgas-Recyclings durch Darmmikroben bei der Reduzierung der Deuterium-Last in den Mitochondrien des Wirts: Ist Trimethylaminoxid ein Deuterium-Sensor?", "journal": "Metabolomics : Official journal of the Metabolomic Society", "authors": "Seneff et al.", "author_search": "seneff seneff", "doi": "10.1007/s11306-026-02443-3", "doi_url": "https://doi.org/10.1007/s11306-026-02443-3", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/42050215/", "url": "https://h2medicine.org/studies/study-seneff-2026-essential-recycling-gut-microbes/", "methods": [ "inhalation" ], "indications": [ "diabetes", "metabolic", "liver", "neurology", "cardiovascular", "cancer", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2026 · Seneff — The essential role of hydrogen gas recycling by gut microbes in reducing deuterium load in host mitochondria: is trimethylamine oxide a deuterium sensor?", "summary": "This hypothesis paper proposes that the gut microbiome's recycling of molecular hydrogen plays a role in keeping mitochondria supplied with deuterium-depleted water — and that TMAO (a gut-derived metabolite elevated in many chronic diseases) may function as a marker for impaired deuterium management. The idea connects microbiome health, mitochondrial bioenergetics, and dietary choline in a speculative but detailed framework. This is not an interventional study — it is a theoretical hypothesis with no clinical trial data. (Metabolomics, 2026.)", "assessment": "Evidence level: theoretical review / hypothesis paper (EV 4 — lowest on the evidence hierarchy). No original experimental data are presented. The deuterium-TMAO-H₂ recycling framework is novel and stimulating but remains speculative. The claim about synthetic vs. natural choline and TMAO is based on a single cited mouse study with fully deuterated methyl groups — an extreme experimental condition, not a dietary scenario. Limitations to state clearly: no controlled human or animal intervention; key claims have not been independently replicated; the hypothesis conflates several complex biological systems. This paper is appropriately engaged as a thought-provoking perspective, not as evidence for any clinical application of H₂.", "abstract": "BACKGROUND: The human gut microbiome plays many essential roles, but an often-overlooked role is to maintain an abundant supply of deuterium depleted (deupleted) nutrients to fuel the host mitochondria. Excess deuterium (heavy hydrogen) damages mitochondrial ATP synthase nanomotors, leading to a decrease in matrix water production with increased reactive oxygen species (ROS) and inefficient ATP production. A microbial metabolite, trimethylamine N-oxide (TMAO) is a powerful signaling molecule whose plasma levels are high in association with many chronic diseases, including diabetes, fatty liver disease, and atherosclerosis, as well as cancer and dementia. Thus, TMAO is an important gut-host signaling molecule that serves as a marker for an imbalanced microbiome that is unable to fully metabolize trimethylamine (TMA), an important step in maintaining a deupleted nutrient supply. AIM OF REVIEW: In this paper, we present a hypothesis that TMAO is a marker for deuterium overload in the methylation pathway, in addition to its role as an indicator of a disrupted gut microbiome. The original study that brought attention to TMAO involved feeding mice synthetic choline with fully deuterated methyl groups. Fully deuterated TMAO was subsequently detected in the plasma. By contrast, a diet rich in eggs, a natural source of choline (a precursor to TMAO), does not raise TMAO levels. Many of the pathologies that are linked to elevated TMAO can also be viewed as strategies to promote the supply of deupleted water to the mitochondria, systemically. KEY SCIENTIFIC CONCEPTS: The mantra that \"food is medicine\" is well supported by the powerful role that gut dysbiosis plays in influencing human health and disease.", "conclusion": "Many of the pathologies that are linked to elevated TMAO can also be viewed as strategies to promote the supply of deupleted water to the mitochondria, systemically. KEY SCIENTIFIC CONCEPTS: The mantra that \"food is medicine\" is well supported by the powerful role that gut dysbiosis plays in influencing human health and disease." }, { "pmid": "41747800", "year": 2026, "title": "The protective effects of molecular hydrogen in sepsis-associated encephalopathy: current status.", "title_en": null, "title_de": "Die schützenden Wirkungen von molekularem Wasserstoff bei sepsisassoziierter Enzephalopathie: aktueller Stand.", "journal": "European journal of pharmacology", "authors": "Dumbuya et al.", "author_search": "dumbuya dumbuya", "doi": "10.1016/j.ejphar.2026.178693", "doi_url": "https://doi.org/10.1016/j.ejphar.2026.178693", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41747800/", "url": "https://h2medicine.org/studies/study-dumbuya-2026-protective-sepsis-associated-encephalopathy/", "methods": [ "unspecified" ], "indications": [ "liver", "neurology", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2026 · Dumbuya — The protective effects of molecular hydrogen in sepsis-associated encephalopathy: current status.", "summary": "Sepsis-associated encephalopathy (SAE) — brain dysfunction that develops during severe infections — currently has no specific approved therapy. This review summarizes preclinical evidence that molecular hydrogen (H₂) may help by reducing oxidative stress, neuroinflammation, and mitochondrial damage in the brain. No human clinical trial data for H₂ in SAE is presented; existing evidence comes from animal models only. Treatment protocols are not yet standardized. (European Journal of Pharmacology, 2026.)", "assessment": "Evidence level: narrative review (EV 4). No original experimental data; synthesis of preclinical animal literature only. This is a useful orientation paper that accurately maps the proposed mechanisms and current research gaps. Limitations clearly stated: zero human intervention trials in SAE; heterogeneous animal study protocols make cross-study comparison difficult; optimal dose, timing, and administration route remain undefined; no long-term safety data in humans. Bottom line: H₂ is a plausible but entirely unproven candidate for SAE neuroprotection — much more research is needed before any clinical translation.", "abstract": "Sepsis-associated encephalopathy (SAE) is a severe neurological complication that arises in patients with sepsis, characterised by cognitive impairment and neurological dysfunction. Mechanisms contributing to SAE include oxidative stress, inflammation, mitochondrial dysfunction, and blood-brain barrier disruption. Recent studies indicate that molecular hydrogen (H2) offers therapeutic benefits for SAE due to its antioxidant and anti-inflammatory properties. H2 therapy has shown promise in alleviating oxidative stress, neuroinflammation, and neuronal damage linked to SAE, primarily through scavenging reactive oxygen species, suppressing astrocyte and microglia activation, and mitigating mitochondrial dysfunction. However, variations in treatment protocols (such as dosage, delivery methods, and administration routes) limit the generalizability of findings. Despite these challenges, H2 therapy is well-tolerated with minimal adverse effects. This review synthesises the current evidence on H2 therapy in SAE and highlights key directions for future research, focusing on standardising protocols, optimising treatment regimens, and investigating long-term impacts.", "conclusion": "Despite these challenges, H2 therapy is well-tolerated with minimal adverse effects. This review synthesises the current evidence on H2 therapy in SAE and highlights key directions for future research, focusing on standardising protocols, optimising treatment regimens, and investigating long-term impacts." }, { "pmid": "41641928", "year": 2026, "title": "New progress in hydrogen-synergistic diagnostic and therapeutic nanoplatforms for tumor treatment.", "title_en": null, "title_de": "Neue Fortschritte bei wasserstoff-synergistischen diagnostischen und therapeutischen Nanoplattformen für die Tumorbehandlung.", "journal": "Biomaterials science", "authors": "Shi et al.", "author_search": "shi shi", "doi": "10.1039/d5bm01802a", "doi_url": "https://doi.org/10.1039/d5bm01802a", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41641928/", "url": "https://h2medicine.org/studies/study-shi-2026-progress-synergistic-diagnostic-therapeutic/", "methods": [ "unspecified" ], "indications": [ "cancer" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2026 · Shi — New progress in hydrogen-synergistic diagnostic and therapeutic nanoplatforms for tumor treatment.", "summary": "This review maps the emerging field of hydrogen-synergistic diagnostic and therapeutic nanoplatforms (HSDT-NPs): engineered nanomaterials that combine H₂ therapy with other cancer treatment strategies to increase specificity and effectiveness at the tumor site. The paper is a technical overview of nanoplatform design strategies — no human clinical data are presented; this is entirely a laboratory and animal research domain. (Biomaterials Science, 2026.)", "assessment": "Evidence level: narrative/technical review (EV 4). No original experimental data; no human trial data; summarizes laboratory and animal research on H₂ nanoplatforms in oncology. Limitations clearly stated: all described nanoplatform systems are preclinical; human translation faces major hurdles (nanoparticle safety, immune response, manufacturing, regulatory approval); H₂ production at tumor site via nanoplatforms is a promising concept but unproven in humans. Bottom line: an interesting forward-looking review for researchers working at the intersection of nanomedicine and H₂ biology — not actionable clinical evidence.", "abstract": "Hydrogen synergistic therapy, an emerging and promising strategy in tumor treatment, has been bolstered by nanotechnology to establish a stable and multifunctional foundation for its implementation. Hydrogen-synergistic diagnostic and therapeutic nanoplatforms (HSDT-NPs), a novel type of tool for tumor treatment, integrate hydrogen therapy with various tumor diagnostic and therapeutic strategies, significantly enhancing the efficiency and specificity of tumor treatment, which is crucial for achieving precision therapy at the tumor site. The construction of HSDT-NPs relies on the design of hydrogen nanomaterials and the selection and assembly of synergistic units. Through HSDT-NPs, the synergistic effects between hydrogen therapy and other strategies are markedly enhanced, not only improving the efficacy of traditional therapies on tumors but also effectively protecting normal cells. Based on different material types, this study explores the construction strategies of HSDT-NPs. Subsequently, focusing on the collaborative treatment modes, it delves into the synergistic mechanisms of HSDT-NPs. Our work aims to offer new perspectives and innovative approaches for advancing cancer treatment based on hydrogen therapy research.", "conclusion": "Subsequently, focusing on the collaborative treatment modes, it delves into the synergistic mechanisms of HSDT-NPs. Our work aims to offer new perspectives and innovative approaches for advancing cancer treatment based on hydrogen therapy research." }, { "pmid": "41496215", "year": 2026, "title": "Revisiting molecular hydrogen signaling in mitochondria: Is the Rieske protein the entry point or a downstream sentinel?", "title_en": null, "title_de": "Erneute Betrachtung der molekularen Wasserstoff-Signalübertragung in Mitochondrien: Ist das Rieske-Protein der Eintrittspunkt oder ein nachgeschalteter Wächter?", "journal": "Redox biology", "authors": "Ostojic", "author_search": "ostojic ostojic", "doi": "10.1016/j.redox.2026.104003", "doi_url": "https://doi.org/10.1016/j.redox.2026.104003", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41496215/", "url": "https://h2medicine.org/studies/study-ostojic-2026-revisiting-signaling-mitochondria-rieske/", "methods": [ "unspecified" ], "indications": [ "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2026 · Ostojic — Revisiting molecular hydrogen signaling in mitochondria: Is the Rieske protein the entry point or a downstream sentinel?", "summary": "A new paper demonstrated that H₂ rapidly inhibits mitochondrial Complex III via the Rieske iron-sulfur protein (RISP) — challenging the established view of H₂ as merely a free-radical scavenger. This commentary broadens that picture: RISP may not be the only mitochondrial entry point for H₂ signaling. Ostojic proposes that other iron-sulfur proteins (SDHB, Complex I subunits, CISD family) are equally credible candidates, and calls for comparative experimental studies to determine the true primary target. This is a perspective paper — no new experimental data. (Redox Biology, 2026.)", "assessment": "Evidence level: perspective/commentary (EV 4). No experimental data; responds to and extends an existing published finding. Ostojic is a recognized H₂ researcher with expertise in mitochondrial biochemistry, and the commentary is scientifically grounded. Limitations clearly stated: purely theoretical — the proposed alternative candidates (SDHB, Complex I subunits, CISD proteins) have not yet been experimentally tested as H₂ targets; the framework is a hypothesis, not a demonstrated result. Bottom line: a valuable mechanistic commentary that opens a testable scientific debate about how H₂ signals within mitochondria — no implications for current use or dosing.", "abstract": "A recent study published in Redox Biology (Volume 88, December 2025, 103952) demonstrates that molecular hydrogen (H2) rapidly suppresses mitochondrial Complex III activity through a mechanism involving the Rieske iron-sulfur protein (RISP) and subsequent LONP1-dependent proteolysis, challenging the long-standing view of H2 as merely a selective radical scavenger. While these findings compellingly identify RISP as a key mediator of mitochondrial responses to H2, its designation as the primary molecular target warrants broader consideration. From an evolutionary and structural standpoint, RISP belongs to a wider family of hydrogenase-like mitochondrial redox proteins that retain ancient iron-sulfur architectures. Proteins such as succinate dehydrogenase subunit B (SDHB), iron-sulfur subunits of Complex I, and CISD family [2Fe-2S] proteins share comparable redox logic and strategic positioning within mitochondrial bioenergetic networks. Here, these candidates are prioritized and placed into a hierarchical, testable framework, and specific comparative structural, biochemical, and proteostatic approaches are proposed to define the true molecular entry point of H2 signaling in human mitochondria.", "conclusion": "Proteins such as succinate dehydrogenase subunit B (SDHB), iron-sulfur subunits of Complex I, and CISD family [2Fe-2S] proteins share comparable redox logic and strategic positioning within mitochondrial bioenergetic networks. Here, these candidates are prioritized and placed into a hierarchical, testable framework, and specific comparative structural, biochemical, and proteostatic approaches are " }, { "pmid": "41482991", "year": 2026, "title": "Medical Gases as Emerging Regulators of Paediatric Endocrine and Neurodevelopmental Pathways: A Mini-Review.", "title_en": null, "title_de": "Medizinische Gase als aufkommende Regulatoren pädiatrischer endokriner und neuronaler Entwicklungspfade: Ein Mini-Review", "journal": "Acta paediatrica (Oslo, Norway : 1992)", "authors": "Paparella et al.", "author_search": "paparella paparella", "doi": "10.1111/apa.70429", "doi_url": "https://doi.org/10.1111/apa.70429", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41482991/", "url": "https://h2medicine.org/studies/study-paparella-2026-medical-gases-emerging-regulators/", "methods": [ "unspecified" ], "indications": [ "liver", "neurology", "eye", "joints-rheumatology", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2026 · Paparella — Medical Gases as Emerging Regulators of Paediatric Endocrine and Neurodevelopmental Pathways: A Mini-Review", "summary": "Gaseous signalling molecules — including molecular hydrogen (H₂), nitric oxide, carbon monoxide and hydrogen sulphide — are increasingly recognised as modulators of the developing brain and endocrine system in children. This mini-review surveys preclinical and clinical literature from 2007–2025 on how these gasotransmitters influence synaptic plasticity, neurotransmission, bone biology and puberty control. The authors highlight particular relevance for conditions marked by oxidative stress, such as autism spectrum disorder, ADHD, and chromosomal syndromes including Klinefelter and Turner. (Acta Paediatrica, 2026.)", "assessment": "This is a literature overview (mini-review), not an original experiment. No new clinical data are presented; the authors synthesise existing preclinical and early clinical work on several medical gases together. H₂-specific evidence within this review is embedded among multiple gases and remains mostly preclinical. Conclusions about therapeutic potential in children are speculative and appropriately framed as future directions. Readers should not interpret this as clinical evidence for H₂ therapy in paediatric endocrine or neurodevelopmental conditions.", "abstract": "AIM: Medical gases, including nitric oxide, carbon monoxide, hydrogen sulphide and molecular hydrogen, have emerged as key regulators of redox balance and cellular signalling. This mini-review examines their relevance to paediatric endocrine and neurodevelopmental pathways, domains particularly sensitive to oxidative and inflammatory disturbances. METHODS: We surveyed preclinical and clinical studies published between 2007 and 2025 on gas-mediated regulation of metabolic-redox homeostasis, bone biology, pubertal control and neurodevelopment. Additional attention was given to conditions marked by oxidative stress, such as Klinefelter and Turner syndromes. RESULTS: Evidence shows that gasotransmitters modulate synaptic plasticity, neurotransmission and neuroinflammation, influencing disorders such as autism spectrum disorder, attention-deficit/hyperactivity disorder and outcomes after perinatal hypoxia. They also participate in metabolic regulation, osteogenesis, osteoclast activity and hypothalamic control of puberty. These mechanistic insights highlight the emerging translational potential of gas-mediated pathways in paediatric health. CONCLUSION: Although paediatric clinical applications remain limited, advances in omics-based profiling, mechanistic studies and biomaterial-supported gas delivery are rapidly expanding the therapeutic horizon. Integrating gasotransmitter biology into paediatric endocrinology and neurodevelopment may support future diagnostic, preventive and targeted therapeutic strategies.", "conclusion": "Although paediatric clinical applications remain limited, advances in omics-based profiling, mechanistic studies and biomaterial-supported gas delivery are rapidly expanding the therapeutic horizon. Integrating gasotransmitter biology into paediatric endocrinology and neurodevelopment may support future diagnostic, preventive and targeted therapeutic strategies." }, { "pmid": "41449652", "year": 2026, "title": "Emerging Clinical Applications for Molecular Hydrogen.", "title_en": null, "title_de": "Aufkommende klinische Anwendungen für molekularen Wasserstoff", "journal": "Respiratory care", "authors": "Nguyen Puente et al.", "author_search": "nguyen puente nguyen puente", "doi": "10.1177/19433654251398759", "doi_url": "https://doi.org/10.1177/19433654251398759", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41449652/", "url": "https://h2medicine.org/studies/study-nguyenpuente-2026-emerging-applications/", "methods": [ "inhalation" ], "indications": [ "liver", "neurology", "cardiovascular", "cancer", "respiratory", "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2026 · Nguyen Puente — Emerging Clinical Applications for Molecular Hydrogen", "summary": "Inhaled molecular hydrogen (H₂) has accumulated a growing body of encouraging clinical findings across neurological, cardiovascular, oncological and respiratory conditions — yet the evidence base remains constrained by small study sizes, inconsistent methodology, and a lack of standardised delivery systems. This narrative review synthesises current clinical experience and critically examines the field's key limitations. The authors call for validated delivery technologies to enable more rigorous large-scale trials. (Respiratory Care, 2026.)", "assessment": "This is a narrative review, not a systematic review or meta-analysis — no pooled effect sizes are computed. The clinical findings summarised are encouraging but come from a literature characterised by small samples and variable methodology. The authors' call for standardised delivery systems underscores that H₂ inhalation therapy is still in an early clinical development phase. This paper is appropriate for orientation but cannot substitute for individual assessment of the primary trials it references.", "abstract": "Molecular hydrogen (H2) has emerged as a promising therapeutic agent with potential applications across a wide range of conditions, including neurological, cardiovascular, oncologic, and respiratory diseases. Substantial preclinical studies attribute its benefits to selective antioxidant, anti-inflammatory, and cytoprotective properties. Published clinical findings are encouraging, although data are limited by small sample sizes, methodological variability, and the absence of standardized and validated commercially available delivery systems. This narrative review summarizes the current clinical experience with inhaled H2 therapy, discusses key challenges and limitations in the existing literature, and identifies areas of interest for future research, including the development of a validated delivery system to enable broader clinical investigation and application of H2 therapy.", "conclusion": "Published clinical findings are encouraging, although data are limited by small sample sizes, methodological variability, and the absence of standardized and validated commercially available delivery systems. This narrative review summarizes the current clinical experience with inhaled H2 therapy, discusses key challenges and limitations in the existing literature, and identifies areas of interest" }, { "pmid": "41260719", "year": 2026, "title": "Gas Therapies for Neuro-Protection.", "title_en": null, "title_de": "Gastherapien zur Neuroprotektion", "journal": "Critical care clinics", "authors": "Merigo et al.", "author_search": "merigo merigo", "doi": "10.1016/j.ccc.2025.08.004", "doi_url": "https://doi.org/10.1016/j.ccc.2025.08.004", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41260719/", "url": "https://h2medicine.org/studies/study-merigo-2026-therapies-neuro-protection/", "methods": [ "inhalation" ], "indications": [ "neurology", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2026 · Merigo — Gas Therapies for Neuro-Protection", "summary": "Cardiac arrest causes severe neurological damage, and conventional treatment options remain inadequate — but inhaled gas therapies including molecular hydrogen (H₂), nitric oxide, xenon and argon show neuroprotective promise through antioxidant, anti-inflammatory and anti-apoptotic mechanisms. This review in Critical Care Clinics synthesises preclinical and early clinical evidence, while clearly stating that large-scale trials are still needed before these approaches can enter standard post-resuscitation care. (Critical Care Clinics, 2026.)", "assessment": "This is a narrative review — no original data, no pooled effect sizes. H₂ is discussed as one of four medical gases with neuroprotective potential in the post-cardiac-arrest setting; it is not singled out as superior. The mechanistic rationale is well-supported by preclinical work, but the authors are explicit that large clinical trials are still outstanding. This review is appropriate as background reading on the research landscape, not as clinical guidance.", "abstract": "Cardiac arrest (CA) remains a major cause of mortality and neurologic impairment, underscoring the urgent need for innovative neuroprotective strategies. Gas therapies, including inhaled nitric oxide (NO), molecular hydrogen (H2), xenon (Xe), and argon (Ar), have emerged as promising neuroprotective agents. These gases exert protective effects, preserving neurologic function and improving outcomes after CA through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms. Despite promising preclinical and early clinical data, large-scale trials are essential to validate their efficacy, optimize protocols, refine dosing, and ensure clinical translation. Advancing gas therapies into standard post-CA care could revolutionize neuroprotection, offering a paradigm shift in resuscitation medicine.", "conclusion": "Despite promising preclinical and early clinical data, large-scale trials are essential to validate their efficacy, optimize protocols, refine dosing, and ensure clinical translation. Advancing gas therapies into standard post-CA care could revolutionize neuroprotection, offering a paradigm shift in resuscitation medicine." }, { "pmid": "41232804", "year": 2026, "title": "Advances in hydrogen delivery strategies for therapeutic applications.", "title_en": null, "title_de": "Fortschritte bei Strategien zur Wasserstoff-Verabreichung für therapeutische Anwendungen", "journal": "Advanced drug delivery reviews", "authors": "Nguyen et al.", "author_search": "nguyen nguyen", "doi": "10.1016/j.addr.2025.115734", "doi_url": "https://doi.org/10.1016/j.addr.2025.115734", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41232804/", "url": "https://h2medicine.org/studies/study-nguyen-2026-advances-delivery-strategies-therapeutic/", "methods": [ "inhalation", "saline-iv", "drinking-hrw" ], "indications": [ "liver", "cancer", "skin-aging", "immune-system", "oxidative-stress", "fundamentals-safety" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2026 · Nguyen — Advances in hydrogen delivery strategies for therapeutic applications", "summary": "Molecular hydrogen (H₂) has selective antioxidant, anti-inflammatory and anticancer properties — but getting it reliably to target tissues remains the central challenge limiting clinical use. This comprehensive review in Advanced Drug Delivery Reviews catalogues conventional delivery routes (inhalation, H₂-rich water, saline injection), their limitations, and a new generation of advanced delivery systems: nanocarriers, in-situ H₂-generating materials activated by light, sound or electricity, and gut microbiota-based indirect delivery via probiotics and prebiotics. (Advanced Drug Delivery Reviews, 2026.)", "assessment": "This is a technical review — no original clinical data. Its value lies in mapping the delivery engineering landscape, not in providing clinical efficacy evidence. The vast majority of advanced delivery systems described are preclinical or proof-of-concept only. Readers seeking human clinical evidence should consult separate trial reviews; this paper addresses the fundamental bottleneck of how to get H₂ to where it is needed — a prerequisite for future clinical progress.", "abstract": "Molecular hydrogen (H2) has emerged as a promising therapeutic agent owing to its selective antioxidant and anti-inflammatory properties, as well as its ability to modulate cellular signaling, metabolism, and immune responses. Beyond mitigating oxidative stress and inflammation, H2 shows anticancer potential by altering the tumor microenvironment and inducing apoptosis. Despite encouraging findings from preclinical and clinical studies, conventional delivery routes-such as inhalation, oral intake of H2-rich water, or injection of H2-rich saline-face critical limitations in stability, bioavailability, and targeted delivery, impeding clinical translation. This review first outlines the therapeutic mechanisms of H2, including redox regulation, inflammatory modulation, and tumor suppression. It then discusses current delivery approaches, their therapeutic outcomes, and inherent challenges. To overcome these barriers, a variety of advanced H2-delivering systems have been developed, including H2-containing carriers and in situ H2-generating materials based on water-, acid-, and electrochemical reactions. Externally stimulated platforms, such as photo-, sono-, and electro-catalysis-based systems, enable spatiotemporally controlled H2 release in response to disease-specific cues. Additionally, microbiota-targeted approaches involving probiotics and prebiotics offer indirect yet sustained H2 delivery via gut fermentation. The review concludes by addressing key challenges-such as material scalability, biosafety, and integration with existing therapies-and highlights future directions for optimizing H2 delivery through interdisciplinary innovation in materials science and medicine.", "conclusion": "Additionally, microbiota-targeted approaches involving probiotics and prebiotics offer indirect yet sustained H2 delivery via gut fermentation. The review concludes by addressing key challenges-such as material scalability, biosafety, and integration with existing therapies-and highlights future directions for optimizing H2 delivery through interdisciplinary innovation in materials science and med" }, { "pmid": "41144865", "year": 2026, "title": "Stimuli-Responsive Hydrogen Production from Nanomaterials: Design, Regulation and Biomedical Applications.", "title_en": null, "title_de": "Stimuli-responsive Wasserstoffproduktion aus Nanomaterialien: Design, Regulation und biomedizinische Anwendungen", "journal": "Advanced healthcare materials", "authors": "Pan et al.", "author_search": "pan pan", "doi": "10.1002/adhm.202503077", "doi_url": "https://doi.org/10.1002/adhm.202503077", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41144865/", "url": "https://h2medicine.org/studies/study-pan-2026-stimuli-responsive-production-nanomaterials/", "methods": [ "inhalation" ], "indications": [ "liver", "neurology", "cardiovascular", "cancer", "skin-aging", "immune-system", "fundamentals-safety" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2026 · Pan — Stimuli-Responsive Hydrogen Production from Nanomaterials: Design, Regulation and Biomedical Applications", "summary": "H₂ gas has broad therapeutic potential, but its low solubility and lack of targeted delivery limit clinical use — nanotechnology offers a solution through stimuli-responsive nanomaterials that produce H₂ on demand at disease sites. This review systematically covers nanomaterials that generate H₂ under external triggers such as light, ultrasound, magnetic fields or local tissue microenvironments, and explores their applications in cancer therapy, inflammatory diseases, neurovascular protection and antimicrobial treatment. (Advanced Healthcare Materials, 2026.)", "assessment": "This is a technical review of preclinical nanomaterial research — the described systems are not approved for human use and are largely at proof-of-concept or animal-study stage. The review is valuable for researchers in the field of nano-H₂ medicine but does not constitute clinical evidence for H₂ therapy. No human efficacy data are reviewed. The challenges identified — biocompatibility, dosing thresholds, safety standards — underscore that significant development work remains before any of these systems could reach patients.", "abstract": "Hydrogen gas exhibits broad therapeutic potential in the biomedical field. However, low solubility and the lack of targeted delivery limit its clinical application. Nanotechnology offers a solution with externally stimulated responsive nanomaterials capable of controlled hydrogen production under stimuli such as light, ultrasound, magnetic fields, and microenvironments, overcoming traditional delivery limitations. This review systematically summarizes the mechanisms of action of such materials, covering hydrogen evolution mechanisms such as semiconductor catalysis and coordination of chemistry-driven processes, and explores their biomedical applications in cancer therapy, the treatment of inflammatory diseases, organelle and neurovascular protection, antimicrobial therapy, and imaging-guided synergistic treatment. Finally, this review analyzes key challenges, including material biocompatibility and regulation of hydrogen concentration thresholds, and looks ahead to the optimization of material design through multidisciplinary collaboration, the establishment of safety evaluation standards, and the advancement of nanohydrogen medicine from basic research to precise clinical application.", "conclusion": "This review systematically summarizes the mechanisms of action of such materials, covering hydrogen evolution mechanisms such as semiconductor catalysis and coordination of chemistry-driven processes, and explores their biomedical applications in cancer therapy, the treatment of inflammatory diseases, organelle and neurovascular protection, antimicrobial therapy, and imaging-guided synergistic tre" }, { "pmid": "40826940", "year": 2026, "title": "Molecular hydrogen and kidney diseases: a scoping review based on scientometry and data analytics.", "title_en": null, "title_de": "Molekularer Wasserstoff und Nierenerkrankungen: eine Scoping-Review auf Basis von Szientometrie und Datenanalytik", "journal": "Medical gas research", "authors": "Viana et al.", "author_search": "viana viana", "doi": "10.4103/mgr.medgasres-d-25-00047", "doi_url": "https://doi.org/10.4103/mgr.medgasres-d-25-00047", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40826940/", "url": "https://h2medicine.org/studies/study-viana-2026-kidney-diseases-scoping-review/", "methods": [ "unspecified" ], "indications": [ "kidney-dialysis", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2026 · Viana — Molecular hydrogen and kidney diseases: a scoping review based on scientometry and data analytics", "summary": "Acute kidney injury and chronic kidney disease impose enormous burdens globally — and molecular hydrogen (H₂) consistently shows protective effects against apoptosis, fibrosis, inflammation and oxidative stress in kidney disease models. This scoping review combines bibliometric analysis with thematic synthesis of 69 publications, finding clear research gaps including limited international collaboration and a need for standardised clinical trials. The evidence is promising but still predominantly preclinical and Asian-dominated. (Medical Gas Research, 2026.)", "assessment": "This is a scoping review with bibliometric analysis of 69 publications — not a meta-analysis with pooled effect sizes. The evidence reviewed is predominantly preclinical (animal models of kidney injury); the review explicitly calls for more robust clinical trials. Its methodological contribution is the scientometric mapping of the field's publication landscape. Results cannot be directly extrapolated to clinical renoprotective benefit in humans without further trial evidence.", "abstract": "Acute kidney injury and chronic kidney disease impose substantial burdens on healthcare systems worldwide. Molecular hydrogen (H2) has emerged as a potential therapy due to its selective antioxidant, anti-inflammatory, and antiapoptotic properties. The present study reviews evidence on H₂-based renal interventions, examining therapeutic mechanisms, bibliometric trends, and existing research gaps based on data analytics. This scoping review integrates quantitative bibliometric analysis with qualitative thematic synthesis. This integration, uncommon in conventional scoping reviews, reveals important gaps. Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines, 69 publications were identified through Scopus and Web of Science. These publications mostly originated from Asia, particularly China and Japan, with clear peaks of activity in 2019 and 2024, but international collaboration remains limited. H₂ consistently demonstrated protective effects against apoptosis, fibrosis, inflammation, and oxidative stress across acute kidney injury, nephrotoxicity, transplantation, and early chronic kidney disease models. Our findings suggest that hydrogen therapy holds promise for renoprotection in both acute kidney injury and chronic kidney disease. Nonetheless, more robust clinical trials and standardized research methodologies are imperative to facilitate its broader adoption into clinical nephrology practice.", "conclusion": "Our findings suggest that hydrogen therapy holds promise for renoprotection in both acute kidney injury and chronic kidney disease. Nonetheless, more robust clinical trials and standardized research methodologies are imperative to facilitate its broader adoption into clinical nephrology practice." }, { "pmid": "41401441", "year": 2026, "title": "Sixty-minute inhalation of molecular hydrogen decreases blood oxygen saturation but does not alter autonomic cardiac regulation at rest in healthy females: a randomized, double-blind, placebo-controlled crossover study", "title_en": null, "title_de": "Sechzigminütige Inhalation von molekularem Wasserstoff senkt die Blutsauerstoffsättigung, verändert aber die autonome Herzregulation in Ruhe bei gesunden Frauen nicht: eine randomisierte, doppelblinde, placebokontrollierte Crossover-Studie", "journal": "Canadian Journal of Physiology and Pharmacology", "authors": "Grepl et al.", "author_search": "grepl grepl", "doi": "10.1139/cjpp-2025-0228", "doi_url": "https://doi.org/10.1139/cjpp-2025-0228", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41401441/", "url": "https://h2medicine.org/studies/study-grepl-2026-60-minute-inhalation-blood-oxygen-saturation-cardiac-regulation/", "methods": [ "inhalation" ], "indications": [ "fundamentals", "cardiovascular", "womens-health" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2026 · Grepl — Sixty-minute inhalation of molecular hydrogen decreases blood oxygen saturation but does not alter autonomic cardiac regulation at rest in healthy females: a randomized, double-blind, placebo-controlled crossover study", "summary": "One hour of H₂ inhalation at rest lowers blood oxygen saturation minimally (95.9% vs. 96.7%, p ≤ 0.007) without altering autonomic cardiac regulation. In a double-blind placebo crossover in 20 healthy women, the drop was statistically significant but clinically meaningless — heart rate variability stayed unchanged. (Canadian Journal of Physiology and Pharmacology, 2026.)", "assessment": "This study is valuable as safety and mechanism evidence: it shows that H₂ inhalation at rest does not disturb cardiovascular autonomy and only causes a clinically insignificant drop in saturation. Exactly such „negative/null findings“ strengthen the credibility of the H₂ topic, because they show that research does not report only positive results. Notable as sober evidence of the harmlessness of H₂ inhalation at rest. Limitation, stated honestly: very small sample (n = 20), only healthy young women, only rest (no exertion) — no statement on therapeutic benefit. Clean RCT design (evidence level 3).", "abstract": "Molecular hydrogen has gained attention for its potential antioxidant, anti-inflammatory, and ergogenic effects. However, its impact on blood oxygen saturation and autonomic cardiac regulation under resting conditions remains unclear. This randomized, double-blind, placebo-controlled crossover study investigated the effects of a 60 min molecular hydrogen inhalation on oxygen saturation and heart rate variability in healthy females. Twenty physically active participants (22.1 ± 1.6 years) completed two inhalation sessions with either molecular hydrogen or placebo (ambient air), separated by a 7-day washout period. Oxygen saturation and heart rate variability were continuously monitored during the 60 min of inhalation. The results using 60 min averages showed a statistically significant (p ≤ 0.007) decrease in oxygen saturation during molecular hydrogen inhalation (95.9 ± 1.0%) compared to placebo (96.7 ± 0.7%), but this decrease should not be considered clinically significant. No significant changes (all p ≥ 0.32) were observed in time-domain or frequency-domain heart rate variability indices. These findings suggest that, under resting conditions, molecular hydrogen inhalation does not induce functional changes in autonomic cardiac regulation, and the observed reduction in blood oxygen saturation does not compromise homeostatic stability.", "conclusion": "No significant changes (all p ≥ 0.32) were observed in time-domain or frequency-domain heart rate variability indices. These findings suggest that, under resting conditions, molecular hydrogen inhalation does not induce functional changes in autonomic cardiac regulation, and the observed reduction in blood oxygen saturation does not compromise homeostatic stability." }, { "pmid": "41754211", "year": 2026, "title": "Redox Water Consumption Attenuates Exercise-Induced Inflammation and Oxidative Stress in Physically Active Adults: A Randomized Controlled Trial", "title_en": null, "title_de": "Der Konsum von Redox-Wasser dämpft belastungsbedingte Entzündung und oxidativen Stress bei körperlich aktiven Erwachsenen: eine randomisierte kontrollierte Studie", "journal": "Nutrients", "authors": "Stolecka-Warzecha et al.", "author_search": "stolecka-warzecha stolecka-warzecha", "doi": "10.3390/nu18040694", "doi_url": "https://doi.org/10.3390/nu18040694", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41754211/", "url": "https://h2medicine.org/studies/study-stolecka-warzecha-2026-redox-water-exercise-inflammation-oxidative-stress/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise", "oxidative-stress", "immune-system" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2026 · Stolecka-Warzecha — Redox Water Consumption Attenuates Exercise-Induced Inflammation and Oxidative Stress in Physically Active Adults: A Randomized Controlled Trial", "summary": "Eight weeks of hydrogen-enriched redox water dampens the inflammatory surge after intense exercise. In a controlled trial with 40 physically active adults, the inflammatory marker IL-6 fell after the exercise test in the water group, while it rose sharply in the control group (interaction p (Nutrients, 2026.)", "assessment": "Directly relevant to exercise recovery and inflammation regulation, because a concrete biochemical pathway is shown here: a dampened IL-6 response after exertion. This fits mechanistically with the antioxidant profile of H₂. Limitation, stated honestly: the authors themselves stress a pronounced baseline imbalance in the inflammatory values that limits the causal statement — the MDA effect largely disappears after baseline adjustment. Small sample (n = 40). Solid RCT design (evidence level 3), but with clear reservations.", "abstract": "BACKGROUND: Acute high-intensity exercise induces transient inflammatory and oxidative stress responses, mediated by redox-sensitive signaling pathways and reflected by elevations in interleukin-6 (IL-6) and lipid peroxidation products. Modulation of these responses through hydration-based redox interventions remains insufficiently characterized at the biochemical level. OBJECTIVE: This randomized controlled trial investigated whether regular consumption of redox (alkaline) water influences exercise-induced inflammatory and oxidative stress markers in physically active adults. METHODS: Forty physically active adults were randomized into an experimental group (EG; n = 20) and consumed redox water subjected to molecular-level modification, yielding alkaline hydrogen-enriched water (pH 9.2-9.4), or a control group (CG; n = 20) that consumed standard water. After eight weeks of intervention, participants performed a standardized maximal aerobic exercise test. Plasma IL-6 and malondialdehyde (MDA) concentrations were measured at baseline and immediately post-exercise. Statistical analyses included two-way repeated measures ANOVA and ANCOVA. RESULTS: A pronounced group × time interaction was observed for IL-6 (F(1,38) = 36.89, p < 0.001). The EG exhibited a significant post-exercise reduction in IL-6, whereas the CG demonstrated a robust increase. A significant group × time interaction was also detected for MDA (F(1,38) = 4.98, p = 0.029), reflecting stable lipid peroxidation levels in the EG and increased levels in the CG; however, baseline-adjusted analyses indicated that post-exercise MDA differences were largely attributable to initial variability. Hematological and coagulation parameters remained within physiological ranges in both groups. CONCLUSIONS: Redox water intake was associated with lower immediate post-exercise IL-6 compared with controls after baseline adjustment; however, pronounced baseline imbalance limits causal interpretation and warrants confirmation in larger trials with balanced inflammatory profiles. These findings highlight a potential biochemical mechanism linking hydration redox properties with inflammatory regulation during physical stress.", "conclusion": "Redox water intake was associated with lower immediate post-exercise IL-6 compared with controls after baseline adjustment; however, pronounced baseline imbalance limits causal interpretation and warrants confirmation in larger trials with balanced inflammatory profiles. These findings highlight a potential biochemical mechanism linking hydration redox properties with inflammatory regulation during physical stress." }, { "pmid": "41545661", "year": 2026, "title": "Exploratory Evaluation of Hydrogen-Rich Water Therapy for Keloid Management: A Double-Blinded Randomized Pilot Trial", "title_en": null, "title_de": "Explorative Evaluation einer Therapie mit wasserstoffreichem Wasser zur Behandlung von Keloiden: eine doppelblinde, randomisierte Pilotstudie", "journal": "Aesthetic Plastic Surgery", "authors": "Kuang et al.", "author_search": "kuang kuang", "doi": "10.1007/s00266-025-05512-5", "doi_url": "https://doi.org/10.1007/s00266-025-05512-5", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41545661/", "url": "https://h2medicine.org/studies/study-kuang-2026-keloid-management-pilot-trial/", "methods": [ "drinking-hrw" ], "indications": [ "skin-aging", "oxidative-stress", "immune-system" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2026 · Kuang — Exploratory Evaluation of Hydrogen-Rich Water Therapy for Keloid Management: A Double-Blinded Randomized Pilot Trial", "summary": "Hydrogen-rich drinking water relieved pain and itching in keloid patients and dampened inflammatory and scar-forming messengers. In a double-blind pilot RCT with 21 patients, VSS scar score and pigmentation fell significantly, the anti-inflammatory messenger IL-10 rose, while VEGF and TGF-β fell. (Aesthetic Plastic Surgery, 2026 — first clinical signals, exploratory.)", "assessment": "Interesting for the skin/scar and anti-aging segment, because an unusual but clinically hard endpoint picture (scar score, messengers) is shown here. Mechanistically consistent with the anti-inflammatory H₂ effect. Limitation, stated honestly: very small sample (n = 21), exploratory pilot — the authors themselves classify it as early signals. Evidence level 2. No basis for treatment promises; but valuable as a scientifically exciting data point for an unusual indication.", "abstract": "BACKGROUND: Clinical or experimental trials have shown that hydrogen-rich water has anti-inflammatory properties, but its use for keloids has not been studied. This research explores HRW's therapeutic potential and mechanism for keloid treatment. METHODS: 21 keloid patients scheduled for two-stage operations were randomly divided into the HRW treatment group (HRW group) and the control group (Con group). The HRW group received hydrogen in their drinking water, while the Con group drank hydrogen-free water. Clinical information was collected. Cytokines related to inflammation, keloid formation, and symptoms were measured using western blotting (WB), qPCR, and ELISA before and after the interventions. RESULTS: Patients reported a significantly lower frequency of pain and pruritus after hydrogen-rich water therapy. The VSS and pigmentation domain scores significantly decreased after hydrogen-rich water therapy. WB and qPCR results showed a significant decrease in the expression of pruritus-related cytokine TRPV1 and keloid-related cytokine HIF-1α after hydrogen-rich water therapy. Anti-inflammatory cytokine IL-10 levels significantly increased after hydrogen-rich water therapy, while inflammation-related cytokines VEGF and TGF-β levels significantly decreased. CONCLUSIONS: Hydrogen-rich water therapy appears to be a safe and promising approach for symptom relief and inflammation modulation in keloid patients. These findings represent an exploratory, double-blinded randomized pilot trial that provides early clinical signals supporting further large-scale investigation. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .", "conclusion": "Hydrogen-rich water therapy appears to be a safe and promising approach for symptom relief and inflammation modulation in keloid patients. These findings represent an exploratory, double-blinded randomized pilot trial that provides early clinical signals supporting further large-scale investigation. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Conte" }, { "pmid": "41859790", "year": 2026, "title": "The combined use of inhaled nitric oxide and molecular hydrogen in patients with post-COVID-19 syndrome", "title_en": null, "title_de": "Der kombinierte Einsatz von inhaliertem Stickstoffmonoxid und molekularem Wasserstoff bei Patienten mit Post-COVID-19-Syndrom", "journal": "Terapevticheskii arkhiv", "authors": "Pozdnyakova et al.", "author_search": "pozdnyakova pozdnyakova", "doi": "10.26442/00403660.2026.03.203537", "doi_url": "https://doi.org/10.26442/00403660.2026.03.203537", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41859790/", "url": "https://h2medicine.org/studies/study-pozdnyakova-2026-inhaled-nitric-oxide-post-covid-19-syndrome/", "methods": [ "inhalation", "bath-topical" ], "indications": [ "respiratory", "oxidative-stress", "immune-system" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2026 · Pozdnyakova — The combined use of inhaled nitric oxide and molecular hydrogen in patients with post-COVID-19 syndrome", "summary": "Combined inhalation of nitric oxide (NO) and molecular hydrogen (H₂) relieves post-COVID syndrome better than NO alone. In a controlled trial with 60 patients, shortness of breath, cough and fatigue improved, the distance in the 6-minute walk test rose, and reactive oxygen species fell — significantly more so only in the combination group (p (Terapevticheskii arkhiv, 2026.)", "assessment": "Relevant for the H₂ inhalation segment and the long-COVID topic that concerns many customers. The study shows a measurable additional benefit of H₂ beyond NO — especially for oxidative stress, the mechanistic core argument of H₂. Limitation, stated honestly: open design (no blinding, so placebo/expectation effects possible), small arms (n = 20), and H₂ was tested only as a co-intervention with NO — the pure H₂ contribution remains unclear. Evidence level 2 (controlled pilot study, not blinded).", "abstract": "BACKGROUND: Medical gases, inhaled nitric oxide (iNO) and molecular hydrogen (iH2), have been used in the therapy for various medical conditions. When combined, these gases have shown to be more effective and safer for patients, and may become a promising treatment option for various diseases рost-COVID-19 syndrome (PS). AIM: To compare the efficacy and safety of combined therapy iNO/iH2 with monotherapy iNO and a control group in patients with respiratory disorders during with PS. MATERIALS AND METHODS: A prospective, open-label, controlled trial involving 60 patients with PS was conducted in parallel groups (the mean age of the participants was 58.1 ± 12.9 years, and the sample consisted of 18 men and 42 women). The participants were randomly assigned to 3 groups: 1 (n = 20) - iNO/iH2 treatment; 2 (n = 20) - only iNO treatment; and 3 (n = 20) - control group. The duration of treatment was 10 days, and the treatment involved inhalation through a nasal cannula for 90 minutes (flow rate of 4 liters per minute, iH2 concentrations < 4%, iNO - 60 pmm). Clinical outcomes were assessed using self-observation diaries, Modified Medical Research Council Dyspnea Scale questionnaires, the \"Language of Dyspnea\" Scale, Fatigue Assessment Scale, Hospital Anxiety and Depression Scale, and Short Form-36 Health Status Survey questionnaires. Additionally, a 6-Minute Walk Test was performed, and indicators of oxidative status in blood serum and microcirculation in the bulbar conjunctiva were measured. RESULTS: The course of iNO/iН2 and iNO led to regression of the clinical manifestations of PS (dyspnea, cough, fatigue), improved the physical and psychological component of quality of life, and contributed to improvement in microcirculation (increased venule diameter and velocity) compared to the control group (p < 0.05). In combination therapy, there was an increase in distance traveled by 6-minute walk test and decrease in reactive oxygen species compared to iNO and control groups (p < 0.05). No serious adverse events were noted. CONCLUSION: The study demonstrates the advantage of the iNO/iH2 course in comparison with iNO and control in the rehabilitation program of patients with PS. The safety and effectiveness of the iNO/iH2 course has been proven in the form of regression of clinical manifestations of PS, improvement of quality of life, exercise tolerance, microcirculation parameters, and restoration of the oxidative status of the body.", "conclusion": "The study demonstrates the advantage of the iNO/iH2 course in comparison with iNO and control in the rehabilitation program of patients with PS. The safety and effectiveness of the iNO/iH2 course has been proven in the form of regression of clinical manifestations of PS, improvement of quality of life, exercise tolerance, microcirculation parameters, and restoration of the oxidative status of the body." }, { "pmid": "42139605", "year": 2026, "title": "Hydration bioanalyses of the effects of hydrogen-rich water (HRW).", "title_en": null, "title_de": "Hydratations-Bioanalysen der Wirkungen von wasserstoffreichem Wasser (HRW)", "journal": "Wiadomosci lekarskie (Warsaw, Poland : 1960)", "authors": "Pesotskaya et al.", "author_search": "pesotskaya pesotskaya", "doi": "10.36740/wlek/218738", "doi_url": "https://doi.org/10.36740/wlek/218738", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/42139605/", "url": "https://h2medicine.org/studies/study-pesotskaya-2026-hydration-bioanalyses-hrw/", "methods": [ "drinking-hrw" ], "indications": [ "kidney-dialysis" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2026 · Pesotskaya — Hydration Bioanalyses of the Effects of Hydrogen-Rich Water (HRW)", "summary": "Twenty-one days of daily hydrogen-rich water intake in healthy volunteers produced statistically significant decreases in hematocrit and blood viscosity, and reduced urine osmolality — all consistent with improved systemic hydration. No signs of red blood cell abnormalities were observed. The study is small (n=10) and uses a device-specific hydrogen preparation, but represents one of the few human studies directly measuring hydration biomarkers with HRW. (Wiadomosci lekarskie, 2026.)", "assessment": "A small, unblinded, single-arm pilot study — no control group, no placebo, no blinding. The results are directionally interesting but cannot exclude confounding factors (e.g., increased total water intake, dietary changes, seasonal variation). The absence of a control group is the primary limitation: the observed hematocrit and osmolality changes could be explained by simply drinking more water, regardless of hydrogen content. The safety signal (no erythrocyte damage) is reassuring. The hydrogen concentration (900–1200 ppb) is within the range used in other published studies. This study should be considered hypothesis-generating, not confirmatory evidence that HRW improves hydration beyond equivalent plain water intake.", "abstract": "OBJECTIVE: Aim: To demonstrate the effects of hydrogen-rich water (HRW) on hydration by examining hematocrit, blood viscosity, and urine osmolality. PATIENTS AND METHODS: Materials and Methods: Hydrogen Evodrop rich water (HEW), produced from a patented device with hydrogen concentration therein 900-1200 ppb or 0.9-1.2 ppm, ORP ranging from -450 to -580 mV, and pH=7.1-7.3. Blood viscosity, hematocrit and urine osmolality had been determined in 10 volunteers (five women and five men) during the 21-day period of HEW intake, under standard dietary conditions. RESULTS: Results: No evidence of erythrocyte agglutination or morphological abnormalities was observed. Urine osmolality in both men and women decreased after HEW consumption, likely due to improved hydration. However, osmolality before the consumption was higher in men compared to women. Both men and women exhibited statistically significant changes in hematocrit and blood viscosity parameters after consuming HEW, which decreased. This suggests improved hydration and reduced blood viscosity. CONCLUSION: Conclusions: These results suggest that measurable hydration effects in the human body may be achieved through regular intake of HEW. The findings of the research support the benefit of the use of HEW in promoting body hydration. The analysis suggests that hematocrit is more closely associated with other factors, such as hydration status and plasma volume following HEW consumption. HEW consumption consistently affected urine osmolality, which may reflect in overall hydration status. Overall, HEW intake produced consistent changes in key hematological and renal hydration markers, indicating favorable effects on blood fluidity and water balance.", "conclusion": "Conclusions: These results suggest that measurable hydration effects in the human body may be achieved through regular intake of HEW. The findings of the research support the benefit of the use of HEW in promoting body hydration. The analysis suggests that hematocrit is more closely associated with other factors, such as hydration status and plasma volume following HEW consumption. HEW consumption consistently affected urine osmolality, which may reflect in overall hydration status. Overall, HEW" }, { "pmid": "42049414", "year": 2026, "title": "Adjunctive Molecular Hydrogen Capsule Therapy in Empyema Complicated by Chronic Inflammatory Demyelinating Polyneuropathy: A Case Report.", "title_en": null, "title_de": "Adjunktive Therapie mit molekularem Wasserstoff in Kapselform bei Empyem mit komplizierender chronischer inflammatorischer demyelinisierender Polyneuropathie: Ein Fallbericht", "journal": "In vivo (Athens, Greece)", "authors": "Li et al.", "author_search": "li li", "doi": "10.21873/invivo.14337", "doi_url": "https://doi.org/10.21873/invivo.14337", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/42049414/", "url": "https://h2medicine.org/studies/study-li-2026-adjunctive-capsule-empyema-complicated/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise", "neurology", "respiratory", "immune-system", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2026 · Li — Adjunctive Molecular Hydrogen Capsule Therapy in Empyema Complicated by Chronic Inflammatory Demyelinating Polyneuropathy: A Case Report", "summary": "A 76-year-old man with a rare combination of chest infection (Stage II empyema) and an autoimmune nerve disorder (CIDP) recovered after surgery plus adjuvant oral molecular hydrogen therapy. Detailed immune monitoring showed that H₂ appeared to selectively promote the death of overactivated inflammatory immune cells while preserving protective regulatory cells — a pattern consistent with immune homeostasis rather than broad immunosuppression. (In Vivo, 2026.)", "assessment": "A case report provides the lowest level of clinical evidence. No causal inference about H₂ is possible from a single uncontrolled case. The patient recovered — but the simultaneous surgical treatment (VATS decortication), post-operative care, and the natural course of CIDP management all contributed. The immunophenotyping data is genuinely interesting and generates testable hypotheses about H₂'s immunomodulatory mechanism. The honest assessment: this report is valuable as a detailed clinical observation that informs future controlled studies — it does not prove that H₂ caused the recovery. The authors themselves use appropriately cautious language ('may act').", "abstract": "BACKGROUND/AIM: The management of Stage II empyema complicated by chronic inflammatory demyelinating polyneuropathy (CIDP) presents a formidable clinical challenge due to the precarious balance required between aggressive infection control and the modulation of immune-mediated neurological frailty. We report a complex case of comorbid empyema and CIDP successfully managed with a multidisciplinary approach and adjuvant molecular hydrogen (H2) therapy. CASE REPORT: A 76-year-old male with CIDP presented with acute respiratory failure secondary to Stage II empyema. Following video-assisted thoracoscopic surgery (VATS) decortication, the patient exhibited systemic hyperinflammation and immune exhaustion. Adjuvant oral molecular hydrogen therapy was initiated during the critical phase. Longitudinal immunophenotyping was performed to monitor the therapeutic response. Clinical recovery coincided with profound immunological remodeling. We observed a cell-specific up-regulation of fas cell surface death receptor (Fas) expression in hyper-activated naïve and effector cytotoxic T cells (Tc), suggesting a H2-facilitated apoptotic clearance of pro-inflammatory lineages. Conversely, the helper T-cell (Th) reservoir was preserved. Recovery was further characterized by the consistent restoration of intermediate and post-germinal center memory B-cell populations, coupled with a substantial augmentation of suppressive T and B-cell subsets (Tregs and Bregs). This shift toward immune homeostasis prevented secondary autoimmune flares and facilitated successful discharge. CONCLUSION: Molecular hydrogen may act as a systemic bioregulator that fosters immune homeostasis by selectively targeting hyper-activated effector cells while promoting regulatory cell recovery. This dual antioxidant and immunomodulatory capacity positions H2 as a promising adjuvant therapy for complex infectious and neuroinflammatory conditions.", "conclusion": "Molecular hydrogen may act as a systemic bioregulator that fosters immune homeostasis by selectively targeting hyper-activated effector cells while promoting regulatory cell recovery. This dual antioxidant and immunomodulatory capacity positions H2 as a promising adjuvant therapy for complex infectious and neuroinflammatory conditions." }, { "pmid": "42049119", "year": 2026, "title": "Hydrogen gas inhalation alleviated cerebral ischemia/reperfusion injury by regulating mitophagy in SH-SY5Y cells and mice via PTEN-induced kinase 1/Parkin pathway.", "title_en": null, "title_de": "Wasserstoffgas-Inhalation linderte zerebrale Ischämie-/Reperfusionsschäden durch Regulierung der Mitophagie in SH-SY5Y-Zellen und Mäusen über den PTEN-induzierten Kinase-1/Parkin-Signalweg.", "journal": "Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association", "authors": "Wang et al.", "author_search": "wang wang", "doi": "10.1016/j.jstrokecerebrovasdis.2026.108645", "doi_url": "https://doi.org/10.1016/j.jstrokecerebrovasdis.2026.108645", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/42049119/", "url": "https://h2medicine.org/studies/study-wang-2026-inhalation-alleviated-cerebral-ischemia/", "methods": [ "inhalation" ], "indications": [ "neurology", "cardiovascular", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2026 · Wang — Hydrogen gas inhalation alleviated cerebral ischemia/reperfusion injury by regulating mitophagy in SH-SY5Y cells and mice via PTEN-induced kinase 1/Parkin pathway.", "summary": "Inhaling molecular hydrogen (H₂) after a stroke-like event (cerebral ischemia/reperfusion) significantly reduced brain tissue damage, neuronal death, and neurological deficits in both mouse models and cell cultures. The key mechanism: H₂ activates the Nrf2/PINK1/Parkin pathway, which clears damaged mitochondria via mitophagy and suppresses both oxidative stress and inflammatory signaling. These are preclinical findings; no human trials are reported here. (Journal of Stroke and Cerebrovascular Diseases, 2026.)", "assessment": "A methodologically solid preclinical study that advances mechanistic understanding of H₂ neuroprotection. The dual in-vivo/in-vitro design with pharmacological pathway confirmation (ML385 Nrf2 inhibition) strengthens the causal argument. Limitations to state honestly: all evidence is from rodent models and cancer-derived cell lines — no human data, no safety or dosing data for clinical use. MCAO/R in mice is an imperfect model of human ischemic stroke. The paper does not quantify H₂ concentration during inhalation or compare doses. Bottom line: a meaningful mechanistic contribution to H₂ neuroscience, not a basis for clinical recommendations.", "abstract": "BACKGROUND: Cerebral ischemia-reperfusion injury (CIRI) causes severe neuronal damage following restoration of cerebral blood flow, and mitochondrial dysfunction acts as a core pathological driver of this process. Molecular hydrogen (H₂) has exhibited promising neuroprotective effects in multiple neurological disease models, yet it remains unclear whether H2 alleviates CIRI by modulating mitophagy and its upstream regulatory signaling pathways. METHODS: In vivo experiments were performed using male C57BL/6 mice subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) with mice randomly divided into three groups: Sham group, MCAO/R group, and MCAO/H₂ group. In vitro, human neuroblastoma SH-SY5Y cells were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R), with four experimental groups: Control group, OGD/R group, OGD/R + H₂ group, and OGD/R + H₂+ML385 group (5 μM ML385, a specific Nrf2 inhibitor, pretreated for 1 h before OGD). Neurological function was assessed via neurological deficits score (zea-Longa); Cerebral infarct volume was measured by TTC staining; Neuronal histopathological damage and apoptosis were evaluated via HE, Nissl, and TUNEL staining; Cell viability was detected using CCK-8 assay; Cell apoptosis, mitochondrial reactive oxygen species (ROS) levels, and mitochondrial membrane potential (MMP) were analyzed by flow cytometry; Protein expression levels were quantified by Western blotting. RESULTS: In vivo experiments demonstrated that H₂ inhalation markedly alleviated neurological deficits, reduced cerebral infarct volume and histopathological damage, inhibited neuronal apoptosis, and promoted mitophagy in MCAO/R mice. In SH-SY5Y cells, H₂ treatment significantly improved cell viability, attenuated oxidative stress and mitochondrial dysfunction, and enhanced mitophagy via activation of the PINK1/Parkin pathway. Mechanistically, H₂ maintained cellular redox homeostasis, cleared damaged mitochondria, upregulated the Nrf2/HO-1 antioxidant pathway, and suppressed NF-κB-mediated inflammatory signaling. Notably, inhibition of Nrf2 with ML385 significantly reversed the mitochondrial protective and anti-apoptotic effects of H₂ in OGD/R-exposed cells. CONCLUSION: Our findings revealed that H2 exerts significant neuroprotective effects against CIRI by attenuating oxidative stress, inhibiting neuronal apoptosis, and improving mitochondrial function. These effects are closely associated with the activation of the Nrf2/PINK1/Parkin-mediated mitophagy pathway, highlighting H₂ as a potential therapeutic method for CIRI.", "conclusion": "Our findings revealed that H2 exerts significant neuroprotective effects against CIRI by attenuating oxidative stress, inhibiting neuronal apoptosis, and improving mitochondrial function. These effects are closely associated with the activation of the Nrf2/PINK1/Parkin-mediated mitophagy pathway, highlighting H₂ as a potential therapeutic method for CIRI." }, { "pmid": "42035551", "year": 2026, "title": "Molecular hydrogen suppresses gut inflammation and pyroptosis in ulcerative colitis through promoting PKM2 lactylation to block NLRP3 inflammasome activation.", "title_en": null, "title_de": "Molekularer Wasserstoff unterdrückt Darmentzündung und Pyroptose bei Colitis ulcerosa durch Förderung der PKM2-Laktylierung zur Blockierung der NLRP3-Inflammasom-Aktivierung.", "journal": "International immunopharmacology", "authors": "Yang et al.", "author_search": "yang yang", "doi": "10.1016/j.intimp.2026.116726", "doi_url": "https://doi.org/10.1016/j.intimp.2026.116726", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/42035551/", "url": "https://h2medicine.org/studies/study-yang-2026-suppresses-gut-inflammation-pyroptosis/", "methods": [ "drinking-hrw" ], "indications": [ "immune-system", "fundamentals-safety" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2026 · Yang — Molecular hydrogen suppresses gut inflammation and pyroptosis in ulcerative colitis through promoting PKM2 lactylation to block NLRP3 inflammasome activation.", "summary": "Molecular hydrogen (H₂) reduces intestinal inflammation and cell death (pyroptosis) in ulcerative colitis by promoting a post-translational modification of the enzyme PKM2 — called lactylation — which in turn prevents the NLRP3 inflammasome from triggering inflammatory cascades. This mechanism was demonstrated in human colonic cells, mouse models of colitis, and colon tissue from UC patients. All evidence is preclinical; no human intervention trial is reported. (International Immunopharmacology, 2026.)", "assessment": "A mechanistically innovative preclinical paper that proposes a concrete, testable pathway connecting H₂, metabolic enzyme lactylation, and NLRP3-driven gut inflammation. The use of human colon tissue samples (from UC patients vs. healthy controls) to validate the PKM2 lactylation deficit adds credibility beyond pure animal work. Limitations to state honestly: no human clinical trial; DSS-induced colitis in mice does not fully replicate the complexity of human UC; the study does not test long-term administration or dose-response for H₂; and the lactylation mechanism, while novel, requires independent replication. Bottom line: compelling mechanistic hypothesis for H₂ in UC — not yet clinical evidence.", "abstract": "BACKGROUND: Molecular hydrogen is considered to be able to alleviate the progression of ulcerative colitis (UC), whose underlying molecular mechanism remains largely unclear. METHODS: Lipopolysaccharide (LPS)/adenosine triphosphate (ATP)-stimulated human colonic epithelial cells (HCoEpiC) were used to mimic UC model in vitro and were treated with hydrogen-rich medium (HRM). Dextran sulfate sodium (DSS)-induced mice were used to construct UC model in vivo and were administrated by hydrogen-rich water (HRW). Colon tissues from UC patients and healthy volunteers were collected. Release of inflammatory cytokines was detected by ELISA. Cell viability, gut pathological impairment and pyroptosis were assessed by CCK-8 assay, HE staining and transmission electron microscope (TEM). The protein expressions of NLRP3 inflammasome and pyruvate kinase M2 (PKM2) were analyzed by western blot. The interaction between NLRP3 and PKM2 was verified by co-immunoprecipitation (Co-IP) assay. RESULTS: Molecular hydrogen alleviated cell viability inhibition and cytokines production in HCoEpiC cells, and suppressed gut injury, inflammation, pyroptosis and NLRP3 inflammasome activation in mice. PKM2 lactylation was down-regulated in colon tissues of UC patients. Molecular hydrogen treatment promoted PKM2 lactylation without affecting total PKM2 expression. The lactylation inhibitor, sodium oxamate, abolished molecular hydrogen-mediated protective effects on UC. Additionally, molecular hydrogen facilitated the combination between PKM2 and NLRP3 to down-regulate inflammasome activation. This binding between PKM2 and NLRP3 was abolished by disrupting PKM2 lactylation. Furthermore, the structural interaction between lactylated PKM2 and NLRP3 was predicted. CONCLUSION: Molecular hydrogen can promote PKM2 lactylation to restrain NLRP3 inflammasome-mediated pyroptosis and inflammation, thus ameliorating UC progression.", "conclusion": "Molecular hydrogen can promote PKM2 lactylation to restrain NLRP3 inflammasome-mediated pyroptosis and inflammation, thus ameliorating UC progression." }, { "pmid": "41986239", "year": 2026, "title": "Self-Adaptive Hydrogen Nano-Delivery System in Glaucoma Management: Synergistic Antioxidation and Anti-inflammation Therapeutic Strategy.", "title_en": null, "title_de": "Selbstadaptives Wasserstoff-Nanoabgabesystem im Glaukom-Management: Eine synergistische antioxidative und entzündungshemmende therapeutische Strategie", "journal": "ACS nano", "authors": "Zhu et al.", "author_search": "zhu zhu", "doi": "10.1021/acsnano.6c01611", "doi_url": "https://doi.org/10.1021/acsnano.6c01611", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41986239/", "url": "https://h2medicine.org/studies/study-zhu-2026-self-adaptive-nano-delivery/", "methods": [ "unspecified" ], "indications": [ "liver", "eye", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2026 · Zhu — Self-Adaptive Hydrogen Nano-Delivery System in Glaucoma Management: Synergistic Antioxidation and Anti-inflammation Therapeutic Strategy", "summary": "Glaucoma-induced optic nerve damage remains a leading cause of blindness, and current treatments focus only on lowering intraocular pressure — ignoring the oxidative stress and inflammation that drive the underlying damage. In this preclinical study, researchers developed a self-adaptive nanosheet (HyNDs) built on hydrogenated silicene that releases H₂ continuously under physiological conditions, scavenges reactive oxygen species, and — in both cellular and animal models — significantly reduced intraocular pressure while showing negligible toxicity. (ACS Nano, 2026.)", "assessment": "This is a preclinical animal and in-vitro study — results are from mouse models and cell culture, not from humans. The nanoagent HyNDs is a novel material not approved for clinical use. No conclusions about benefit in human glaucoma patients can be drawn from this work. It is a promising proof-of-concept that establishes a new research direction in ocular H₂ delivery; clinical translation would require toxicology studies, primate trials and regulatory approval processes that do not yet exist for this material.", "abstract": "Glaucoma-induced optic nerve damage is known to be a leading cause of blindness worldwide, yet current therapies mainly focus on reducing intraocular pressure without paying significant attention to the oxidative stress and inflammation in ocular tissues. Here, we address this issue by developing a self-adaptive two-dimensional nanosheet that enables sustained hydrogen release in the ocular microenvironment. The nanoagent (termed HyNDs) is constructed by modifying the surface of hydrogenated silicene (SiH), a biocompatible nanosheet that self-decomposes to generate hydrogen under physiological conditions, with d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) polymer. HyNDs exhibit excellent dispersity, making them suitable for ocular delivery, while the TPGS coating ensures prolonged hydrogen release through its shielding effect. We demonstrate that HyNDs can efficiently scavenge oxidative radicals and downregulate the expression of oxidative stress-associated biomarkers in both cellular and animal models, contributing to significantly reduced intraocular pressure. Additionally, the nanoagent exhibits negligible cytotoxicity and adverse effects on ocular tissues. This hydrogen-based therapeutic approach features a dual mechanism of intraocular pressure reduction and oxidative stress mitigation, thereby exhibiting attractive promise for advancing the clinical management of glaucoma.", "conclusion": "Additionally, the nanoagent exhibits negligible cytotoxicity and adverse effects on ocular tissues. This hydrogen-based therapeutic approach features a dual mechanism of intraocular pressure reduction and oxidative stress mitigation, thereby exhibiting attractive promise for advancing the clinical management of glaucoma." }, { "pmid": "41931901", "year": 2026, "title": "Optimization of lens size and ion source parameters for gas chromatography/mass spectrometry-based metabolomics using hydrogen as a carrier gas.", "title_en": null, "title_de": "Optimierung der Linsengröße und der Ionenquellenparameter für gaschromatographie-/massenspektrometriebasierte Metabolomik unter Verwendung von Wasserstoff als Trägergas", "journal": "Journal of chromatography. A", "authors": "Sato et al.", "author_search": "sato sato", "doi": "10.1016/j.chroma.2026.466945", "doi_url": "https://doi.org/10.1016/j.chroma.2026.466945", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41931901/", "url": "https://h2medicine.org/studies/study-sato-2026-optimization-lens-size-ion/", "methods": [ "inhalation" ], "indications": [ "cancer" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2026 · Sato — Optimization of lens size and ion source parameters for gas chromatography/mass spectrometry-based metabolomics using hydrogen as a carrier gas", "summary": "Global helium shortages are pushing analytical chemistry laboratories to adopt hydrogen gas as an alternative carrier gas for GC/MS metabolomics — but hydrogen causes unwanted ion-source reactions that alter fragmentation patterns. This in-vitro technical study developed a hydrogen-deactivated electron ionisation source and found that a 3 mm extraction lens provided the best performance, enabling reproducible metabolomic profiling comparable to helium-based systems. The system was validated on a human colon cancer cell line. (Journal of Chromatography A, 2026.)", "assessment": "This is an in-vitro analytical chemistry study — hydrogen gas is used here as a laboratory carrier gas, not as a medical or therapeutic agent. This study has no implications for H₂ health applications. Its value is entirely technical: it validates a practical workaround for helium scarcity in GC/MS metabolomics. Listing this paper in a health context requires clear labelling that the H₂ use here is purely instrumental.", "abstract": "Gas chromatography/mass spectrometry (GC/MS) is widely employed in metabolomics owing to its high resolution, reproducibility, and compatibility with volatile and semi-volatile compounds. While helium has traditionally been used as the carrier gas, increasing costs and global shortages have prompted the exploration of hydrogen gas as an alternative. Hydrogen offers faster analysis times and reduced ion source contamination but presents challenges, including ion source reactions, which can change compound fragmentation patterns. To address this, a hydrogen-deactivated electron ionization (EI) source has been developed to minimize undesired chemical interactions and improve spectral integrity. In this study, we systematically evaluated the effect of extraction lens sizes (3, 6, and 9 mm) under hydrogen carrier gas conditions using n-alkane and human metabolomic standard solutions. The hydrogen-deactivated ion source equipped with a 3 mm extraction lens provided superior peak symmetry and the highest signal intensities, with acceptable relative standard deviation (RSD) values (i.e., below 30%). In addition, the reproducible fragmentation patterns as those observed with helium carrier gas were obtained for phosphorylated metabolites. Using this optimized configuration, we applied hydrogen gas-based GC/MS to metabolomic profiling of the human colon cancer cell line HCT116 with mutant isocitrate dehydrogenase 1 (IDH1). Key metabolic alterations, including increased levels of the known biomarker 2-hydroxyglutaric acid, were detected in IDH1-mutant cells compared with wild-type cells. These findings establish hydrogen gas-based GC/MS with a hydrogen-deactivated ion source as a robust and reliable platform for metabolomics, offering an effective alternative to helium-based systems.", "conclusion": "Key metabolic alterations, including increased levels of the known biomarker 2-hydroxyglutaric acid, were detected in IDH1-mutant cells compared with wild-type cells. These findings establish hydrogen gas-based GC/MS with a hydrogen-deactivated ion source as a robust and reliable platform for metabolomics, offering an effective alternative to helium-based systems." }, { "pmid": "41923649", "year": 2026, "title": "The Far Side of Carboranes: Anticancer Active Monocations and Ambiently Stable Dications.", "title_en": null, "title_de": "Die abgewandte Seite der Carborane: antikanzerogen aktive Monokationen und umgebungsstabile Dikationen", "journal": "Angewandte Chemie (International ed. in English)", "authors": "Němec et al.", "author_search": "němec němec", "doi": "10.1002/anie.202521595", "doi_url": "https://doi.org/10.1002/anie.202521595", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41923649/", "url": "https://h2medicine.org/studies/study-nemec-2026-far-side-carboranes-anticancer/", "methods": [ "unspecified" ], "indications": [ "cancer", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2026 · Němec — The Far Side of Carboranes: Anticancer Active Monocations and Ambiently Stable Dications", "summary": "Polyhedral carboranes — a class of boron-carbon cage molecules — are biologically stable and normally non-toxic; this in-vitro study shows that positively charged (cationic) carborane variants can display significant anticancer activity against human cancer cell lines, surpassing doxorubicin and cisplatin in potency. Molecular hydrogen (H₂) plays a peripheral chemical role here: its addition triggers a reversible cage-opening reaction in dicationic carboranes via a proton-coupled electron process. This is primarily a synthetic chemistry and cancer cell study, not a hydrogen therapy study. (Angewandte Chemie, 2026.)", "assessment": "This is an in-vitro synthetic chemistry and cancer cell study. Molecular hydrogen is used as a chemical reactant in a novel cage-opening reaction — it is not studied as a therapeutic agent. The anticancer activity reported is for cationic carborane compounds in cell culture, not in animals or humans. No conclusions about H₂ cancer therapy can be drawn from this work. Its relevance to H₂ medicine is marginal and chemical in nature.", "abstract": "Polyhedral carboranes are highly biologically stable, non-toxic clusters. Whereas they are typically encountered in anionic or neutral forms, positively charged species have only recently been discovered. The in vitro antiproliferative effects of selected carboranes were assessed using a panel of human cancer cell lines, and off-target toxicity was evaluated at normal cell lines. The results demonstrated significant anticancer activity and a favorable resistance factor (RF ≈ 1) for monocationic carborane o-2a, surpassing the effects of doxorubicin and cisplatin. In pursuit of even more efficient substrates, the first dicationic polyhedral boranes were synthesized. These water-stable dications exhibit a reversible closo-/nido- cage opening, triggered either by a strong base (DMAP) or by a combination of triethylamine and molecular hydrogen, and reversed upon the addition of acid. The former transformation proceeds without a redox change, while the latter involves a H2/2H+ conversion in a proton-coupled electron process.", "conclusion": "These water-stable dications exhibit a reversible closo-/nido- cage opening, triggered either by a strong base (DMAP) or by a combination of triethylamine and molecular hydrogen, and reversed upon the addition of acid. The former transformation proceeds without a redox change, while the latter involves a H2/2H+ conversion in a proton-coupled electron process." }, { "pmid": "41906653", "year": 2026, "title": "Hydrogen-Enriched Hyaluronic Acid Dressing Ameliorates Diabetic Foot Ulcer via Promoting Mitophagy.", "title_en": null, "title_de": "Wasserstoffangereicherter Hyaluronsäure-Wundverband verbessert das diabetische Fußulkus durch Förderung der Mitophagie", "journal": "Journal of diabetes", "authors": "Xu et al.", "author_search": "xu xu", "doi": "10.1111/1753-0407.70209", "doi_url": "https://doi.org/10.1111/1753-0407.70209", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41906653/", "url": "https://h2medicine.org/studies/study-xu-2026-enriched-hyaluronic-acid-dressing/", "methods": [ "saline-iv" ], "indications": [ "diabetes", "cardiovascular", "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2026 · Xu et al. — Hydrogen-Enriched Hyaluronic Acid Dressing Ameliorates Diabetic Foot Ulcer via Promoting Mitophagy", "summary": "A hyaluronic acid dressing enriched with molecular hydrogen accelerated wound healing in diabetic foot ulcer patients and, in parallel laboratory experiments, activated the cellular „self-cleaning“ programme for damaged mitochondria (mitophagy). The study combined a clinical intervention (wound dressing plus negative-pressure therapy) with cell-culture experiments to identify the SIRT3/FOXO3A/PINK1–PARKIN signalling cascade as the likely mechanism. (Journal of Diabetes, 2026.)", "assessment": "An innovative proof-of-concept study that links H₂ for the first time to the SIRT3-mitophagy axis in diabetic wound healing. The human component (vacuum-assisted closure plus hydrogen-rich saline) shows plausible clinical benefit, but lacks a randomised control group and reports no sample size for the patient cohort. The mechanistic data come primarily from animal and cell-culture experiments. Key limitations: mixed study design (clinical + in vivo + in vitro), no blinded outcome assessment reported, no long-term follow-up, small and undefined patient numbers. The result is hypothesis-generating and justifies a powered randomised controlled trial — it does not yet establish clinical efficacy on its own.", "abstract": "OBJECTIVE: Diabetic foot ulcer (DFU) is one of the most common chronic complications of diabetes. This study developed a hydrogen-enriched hyaluronic acid (HA) dressing and aimed to explore its therapeutic effects and mechanisms in DFU treatment. METHODS: A combination of vacuum-assisted closure (VSD) and hydrogen-rich saline was used to treat DFU patients and assess the clinical outcomes of wound repair. A rat model of DFU was established, and treatment with hydrogen-enriched HA dressing. Subsequently, the protective effects of the dressing were evaluated, including histological studies, the expression of inflammatory factors and angiogenesis markers. Western blot was used to analyze the expression levels of mitophagy-related proteins. In vitro, the role of HA and hydrogen on cell mitochondrial damage, apoptosis, migration, and markers associated with mitophagy pathways in human foreskin fibroblast-1 (HFF-1) was assessed. RESULTS: VSD combined with hydrogen-rich saline significantly enhanced wound healing in patients, while reducing inflammation and oxidative damage. In vivo studies showed that the dressing promoted wound healing, increased collagen deposition, reduced inflammatory cytokines, and enhanced neovascularization. In vitro studies, high glucose induced cell morphological damage and oxidative stress, disrupted mitochondrial membrane potential, leading to apoptosis and attenuating cell migration. However, both HA and hydrogen significantly induced SIRT3 expression and activated the downstream FOXO3A/PINK1-PARKIN signaling pathway, promoting mitochondrial autophagy and reducing cell apoptosis. Furthermore, the SIRT3/SOD2 pathway was also activated, decreasing reactive oxygen species (ROS) production and enhancing migration. CONCLUSION: This study confirmed that the hydrogen-enriched HA dressing has the potential to enhance diabetic wound repair.", "conclusion": "This study confirmed that the hydrogen-enriched HA dressing has the potential to enhance diabetic wound repair." }, { "pmid": "41799190", "year": 2026, "title": "Molecular hydrogen triggers TRPC4-TRPC4AP-dependent reversible calcium transients via extracellular influx.", "title_en": null, "title_de": "Molekularer Wasserstoff löst TRPC4-TRPC4AP-abhängige reversible Calcium-Transienten über extrazellulären Einstrom aus", "journal": "Theranostics", "authors": "Zhao et al.", "author_search": "zhao zhao", "doi": "10.7150/thno.124352", "doi_url": "https://doi.org/10.7150/thno.124352", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41799190/", "url": "https://h2medicine.org/studies/study-zhao-2026-triggers-trpc4-trpc4ap-dependent/", "methods": [ "inhalation" ], "indications": [ "liver", "neurology", "skin-aging" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2026 · Zhao — Molecular hydrogen triggers TRPC4-TRPC4AP-dependent reversible calcium transients via extracellular influx", "summary": "For the first time, researchers have identified a specific ion channel — TRPC4, activated via its binding partner TRPC4AP — as the molecular target through which inhaled hydrogen gas triggers rapid, reversible calcium signals in living cells and in the brains and skin of living mice. These calcium transients enhanced cell motility and were completely absent when TRPC4 or TRPC4AP genes were knocked out, establishing a direct mechanistic link between H₂ and calcium signalling. (Theranostics, 2026.)", "assessment": "This is a mechanistic preclinical study (cell lines + mouse in-vivo models). It makes no therapeutic claims and presents no patient data. Its significance lies in identifying a specific molecular target for H₂ — the TRPC4-TRPC4AP calcium channel axis — which provides a framework for future drug development and helps explain the pleiotropic effects of H₂ across diverse tissues. These findings are not directly transferable to clinical recommendations but represent an important mechanistic advance for the field.", "abstract": "RATIONALE: Hydrogen gas (H2) produces pleiotropic therapeutic actions, but the exact molecular targets and ion-channel-based signaling cascades that underlie these benefits remain elusive. H2 may regulate calcium ion (Ca2+)-dependent processes, but the direct involvement of H2 in Ca2+ signaling and its underlying molecular mechanisms are unknown. We propose that H2 functions as a gaseous messenger that selectively opens a plasma-membrane Ca2+ channel to evoke Ca2+ transients ([Ca2+ i]t) while avoiding cytotoxic overload, thereby offering a mechanism for its diverse biological effects. METHODS: This study employed real-time calcium imaging and CRISPR-Cas9 gene editing, with live-cell imaging to monitor real-time calcium signal intensity in living cells. Two-photon in vivo imaging was applied to detect real-time Ca2+ signals in the brain and dorsal skin of C57BL/6 mice carrying adeno-associated virus-delivered calcium sensors. Live-cell F-actin staining and a wound healing (scratch) assay were used to assess the effects of H2 on cell motility. Protein-protein docking and molecular dynamics simulations were performed to analyze the interaction interface and binding forces between TRPC4 and TRPC4AP in three-dimensional space. Additionally, RNA sequencing was performed to validate downstream biological effects and transcriptional regulation triggered by H2. RESULTS: H2 elicited rapid and reversible [Ca2+ i]t across multiple cell types in a Ca2+- and concentration-dependent manner, an effect that was absent in TRPC4⁻/⁻ or TRPC4AP⁻/⁻ cells. In vivo imaging in mice expressing a genetically encoded Ca²⁺ sensor showed that H2 inhalation elevated Ca2+ signals in the motor cortex (M1 region) and dorsal skin. Functionally, live-cell imaging and wound-healing assays confirmed that H2-induced Ca2+ transients enhanced cell motility. Mechanistically, protein docking revealed a dual-arginine cluster within the CIRB domain of TRPC4; its interaction with TRPC4AP was essential for H2-evoked Ca2+ influx. Mutating these arginines to alanine residues completely abolishing the response. H2 triggered proton efflux and increased intracellular pH. Molecular dynamics simulations indicated that altered pH modulates the binding force between TRPC4 Arg730/Arg731 and TRPC4AP. Transcriptomic analysis further demonstrated that H2 activates calcium-related channels and promotes cytoskeletal remodeling and cell migration. CONCLUSIONS: This study identifies H2 as a novel gaseous signaling molecule that can regulate Ca2+ channels via the TRPC4-TRPC4AP axis. The 730Arg-731Arg motif in TRPC4 serves as a critical H2-sensitive site, enabling dynamic calcium homeostasis without overload. These findings provide a mechanistic framework for developing gas-controlled H2 regenerative therapeutics.", "conclusion": "This study identifies H2 as a novel gaseous signaling molecule that can regulate Ca2+ channels via the TRPC4-TRPC4AP axis. The 730Arg-731Arg motif in TRPC4 serves as a critical H2-sensitive site, enabling dynamic calcium homeostasis without overload. These findings provide a mechanistic framework for developing gas-controlled H2 regenerative therapeutics." }, { "pmid": "41760342", "year": 2026, "title": "Adjunctive Molecular Hydrogen Therapy Modulates T Cell Markers and Reduces Anti-Ro Antibody in Refractory Oral Ulcers of Behçet's Disease and Sjögren's Syndrome: A Case Report.", "title_en": null, "title_de": "Adjunktive Therapie mit molekularem Wasserstoff moduliert T-Zell-Marker und reduziert Anti-Ro-Antikörper bei refraktären oralen Ulzera des Morbus Behçet und des Sjögren-Syndroms: Ein Fallbericht", "journal": "In vivo (Athens, Greece)", "authors": "Lin et al.", "author_search": "lin lin", "doi": "10.21873/invivo.14274", "doi_url": "https://doi.org/10.21873/invivo.14274", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41760342/", "url": "https://h2medicine.org/studies/study-lin-2026-adjunctive-modulates-cell-markers/", "methods": [ "saline-iv", "drinking-hrw" ], "indications": [ "cardiovascular", "joints-rheumatology", "immune-system", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2026 · Lin et al. — Adjunctive Molecular Hydrogen Therapy Modulates T Cell Markers and Reduces Anti-Ro Antibody in Refractory Oral Ulcers of Behçet's Disease and Sjögren's Syndrome: A Case Report", "summary": "A 67-year-old woman with both Behçet's disease and primary Sjögren's syndrome — whose recurrent painful oral ulcers had not responded to years of standard therapy — showed marked clinical improvement and falling anti-Ro antibody levels after adding oral molecular hydrogen capsules to her regimen. Immunophenotyping documented shifts in T-cell subsets consistent with immunomodulation. (In Vivo, 2026.)", "assessment": "A single case report — the weakest level of clinical evidence. No control, no randomisation, no placebo, concurrent multidrug therapy makes causal attribution impossible. The clinically interesting signals (antibody reduction, mucosal healing, T-cell shifts) justify further study but cannot be generalised. Limitations: n = 1, highly complex disease overlap (Behçet's + Sjögren's), extensive background medication, no washout, observer bias not excluded. Useful for hypothesis generation and for showing tolerability; insufficient to guide practice.", "abstract": "BACKGROUND/AIM: Behçet's Disease is a systemic vasculitis affecting both venous and arterial vessels, characterized by painful oral and genital ulcers. Primary Sjögren's Syndrome is an autoimmune disorder mainly targeting exocrine glands, especially the salivary and lacrimal glands, with possible systemic involvement. Molecular hydrogen has emerged as a potential adjuvant therapy due to its antioxidant and immunomodulatory effects. This report evaluates the efficacy of molecular hydrogen as adjunctive therapy for refractory oral ulcers in a patient with Behçet's disease and primary Sjögren's syndrome. CASE REPORT: A 67-year-old Taiwanese woman with Behçet's disease and primary Sjögren's syndrome had recurrent painful oral ulcers and mucosal atrophy since 2018, meeting the International Study Group (ISG) criteria. In 2020, she fulfilled the 2016 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria for Sjögren's syndrome based on Schirmer's test (0/0 mm), positive anti-Ro antibody (29 U/ml), and labial salivary gland biopsy findings. Despite long-term, hydroxychloroquine, colchicine, and monthly high-dose intravenous vitamin C and glutathione, her oral ulcers recurred with petechiae and bleeding. In January 2024, oral molecular hydrogen capsules were added as adjunctive therapy. Over several months, she showed marked clinical improvement, with less mucosal bleeding and decreased anti-Ro antibody levels. Immunophenotyping revealed increased naïve T helper Fas cell surface death receptor-positive (Fas+) and cytotoxic T cell programmed death-1-positive (PD-1+) subsets, suggesting immunomodulatory effects. The therapy was well tolerated, with no major adverse events. By August 2025, oral ulcers had markedly improved, and systemic disease remained stable on maintenance with hydroxychloroquine, azathioprine, corticosteroid infusions, and hydrogen therapy. CONCLUSION: Molecular hydrogen may aid refractory oral ulcers in Behçet's and primary Sjögren's syndromes, with clinical and immunologic benefits.", "conclusion": "Molecular hydrogen may aid refractory oral ulcers in Behçet's and primary Sjögren's syndromes, with clinical and immunologic benefits." }, { "pmid": "41752368", "year": 2026, "title": "Ru-Based NSAIDs as Potential Anticancer Therapeutics.", "title_en": null, "title_de": "Ru-basierte NSAR als potenzielle antikanzerogene Therapeutika", "journal": "Molecules (Basel, Switzerland)", "authors": "Bordoni et al.", "author_search": "bordoni bordoni", "doi": "10.3390/molecules31040589", "doi_url": "https://doi.org/10.3390/molecules31040589", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41752368/", "url": "https://h2medicine.org/studies/study-bordoni-2026-nsaids-anticancer-therapeutics/", "methods": [ "unspecified" ], "indications": [ "cancer", "immune-system" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2026 · Bordoni — Ru-Based NSAIDs as Potential Anticancer Therapeutics", "summary": "Combining anti-inflammatory drugs (NSAIDs) with ruthenium metal centres creates novel compounds with promising anticancer activity in cell culture — and molecular hydrogen (H₂) is produced as a byproduct during synthesis, not as a therapeutic agent. Among five tested ruthenium-NSAID complexes, the salicylic acid variant showed antiproliferative activity against HeLa cancer cells. This is an in-vitro synthetic chemistry study with no direct relevance to H₂ therapy. (Molecules, 2026.)", "assessment": "This is an in-vitro synthetic chemistry and cancer cell study. Molecular hydrogen appears as a synthesis byproduct — it is not investigated as a therapeutic agent. No conclusions about H₂ cancer therapy can be drawn. The paper's relevance to H₂ medicine is incidental; its scientific contribution concerns ruthenium-NSAID metallotherapeutics.", "abstract": "The use of metal-based species bearing existing pharmaceuticals as ligands-often resulting in enhanced bioactivity-represents an attractive strategy for the development of novel therapeutic formulations. In this context, five well-known non-steroidal anti-inflammatory drugs (NSAIDs) were employed to substitute both PPh3 and hydride ligands in [Ru(H)2(CO)(PPh3)3] (1), thereby selectively affording neutral κ2-(O,O)-chelate complexes in satisfactory yields via molecular hydrogen release. Among the obtained species, two complexes coordinating diclofenac (4) and aspirin (5) were further investigated by single-crystal X-ray diffraction (SCXRD). Preliminary biological studies were conducted on the ruthenium-salicylic acid species 2 and ibuprofen 6. The former showed promising antiproliferative activity against HeLa cancer cells, consistent with the well-established role of NSAID-ruthenium(II) complexes as a platform for the development of novel anticancer metallotherapeutics.", "conclusion": "Preliminary biological studies were conducted on the ruthenium-salicylic acid species 2 and ibuprofen 6. The former showed promising antiproliferative activity against HeLa cancer cells, consistent with the well-established role of NSAID-ruthenium(II) complexes as a platform for the development of novel anticancer metallotherapeutics." }, { "pmid": "41749059", "year": 2026, "title": "Transcriptome-Based Evaluation of Hydrogen Gas Effects for Preventing UVA-Induced Photoaging Using an Artificial Skin Model.", "title_en": null, "title_de": "Transkriptombasierte Bewertung der Wirkungen von Wasserstoffgas zur Vorbeugung von UVA-induzierter Photoalterung anhand eines künstlichen Hautmodells", "journal": "Geriatrics & gerontology international", "authors": "Kiyoi et al.", "author_search": "kiyoi kiyoi", "doi": "10.1111/ggi.70401", "doi_url": "https://doi.org/10.1111/ggi.70401", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41749059/", "url": "https://h2medicine.org/studies/study-kiyoi-2026-transcriptome-preventing-uva-induced/", "methods": [ "inhalation" ], "indications": [ "skin-aging", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2026 · Kiyoi — Transcriptome-Based Evaluation of Hydrogen Gas Effects for Preventing UVA-Induced Photoaging Using an Artificial Skin Model", "summary": "Hydrogen gas inhalation may protect skin against UV-A induced photoaging — not just by scavenging free radicals, but by modulating specific gene expression pathways including NRF2-mediated antioxidant defence and the p53-mediated senescence pathway. Using an artificial skin model (a 3D in-vitro tissue construct) exposed to UV-A and then incubated with 1.3 % H₂ gas, this study found that hydrogen suppressed photoaging-related transcriptomic changes that were invisible at the histological level. This is an in-vitro model study — no human subjects were involved. (Geriatrics & Gerontology International, 2026.)", "assessment": "This is an in-vitro study using a 3D artificial skin model — no human subjects were involved. Results are at the level of gene expression in a tissue construct; they cannot be extrapolated to clinical anti-aging effects in real skin. This is preliminary mechanistic evidence only. The transcriptomic findings are interesting and biologically plausible, but human trials would be needed to confirm any photoprotective effect of H₂ inhalation on actual skin aging.", "abstract": "AIM: Intermittent hydrogen gas inhalation has the potential to prevent UVA-induced photoaging by reducing oxidative stress, although the underlying molecular mechanisms remain unclear. Additionally, alternatives to animal experiments are recommended for studies not primarily focused on pathogenesis. This study aimed to evaluate the preventive effects of hydrogen gas on UVA-induced photoaging using a short-term in vitro system with artificial skin. METHODS: Artificial skin was irradiated with UVA at 0, 7, or 10.5 J/cm2/day and incubated for 1 day in a CO2 incubator with or without 1.3% hydrogen gas. This cycle was repeated three times, followed by one-day incubation. Transcriptomic and histological analyses were then performed. RESULTS: UVA at 7 J/cm2/day induced minimal epidermal morphological changes but marked photoaging-related transcriptomic alterations, whereas 10.5 J/cm2/day caused epidermal hypoplasia with excessive apoptosis and only limited transcriptomic changes. In comparisons between the 7 J/cm2/day groups with and without hydrogen, hydrogen modulated UVA-induced biological processes and signaling pathways, including the NRF2-mediated and the NFκB1-RelA-mediated responses, and suppressed the p53-mediated senescence pathway. CONCLUSIONS: This study demonstrated that photoaging-related transcriptomic changes were detectable in artificial skin under a relatively low UVA dose (7 J/cm2/day; total 21 J/cm2) with minimal histological alterations. Furthermore, hydrogen may have a protective effect against UVA-induced cellular stress and senescence, via diffusion through the skin surface, suggesting its potential effectiveness in preventing photoaging. This study provides preliminary evidence that may contribute to the development of future translational research on the utility of molecular hydrogen in UVA-induced photoaging.", "conclusion": "This study demonstrated that photoaging-related transcriptomic changes were detectable in artificial skin under a relatively low UVA dose (7 J/cm2/day; total 21 J/cm2) with minimal histological alterations. Furthermore, hydrogen may have a protective effect against UVA-induced cellular stress and senescence, via diffusion through the skin surface, suggesting its potential effectiveness in preventing photoaging. This study provides preliminary evidence that may contribute to the development of fu" }, { "pmid": "41709731", "year": 2026, "title": "MXene-Engineered MgB2 Nanoprodrugs with Acid-Responsive Hydrogen Evolution for Cooperative Photothermal Cancer Ablation.", "title_en": null, "title_de": "MXene-konstruierte MgB₂-Nanoprodrugs mit säureresponsiver Wasserstoffentwicklung für kooperative photothermische Krebsablation", "journal": "ACS applied materials & interfaces", "authors": "Li et al.", "author_search": "li li", "doi": "10.1021/acsami.5c25581", "doi_url": "https://doi.org/10.1021/acsami.5c25581", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41709731/", "url": "https://h2medicine.org/studies/study-li-2026-mxene-engineered-mgb2-nanoprodrugs/", "methods": [ "inhalation" ], "indications": [ "cancer", "skin-aging", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2026 · Li — MXene-Engineered MgB₂ Nanoprodrugs with Acid-Responsive Hydrogen Evolution for Cooperative Photothermal Cancer Ablation", "summary": "Researchers engineered a nanoparticle system (MgB₂-Ti₃C₂Tₓ@PEG) that releases hydrogen gas specifically within the acidic tumor microenvironment and simultaneously converts near-infrared laser light into heat — combining hydrogen gas therapy with photothermal tumor ablation. In cell culture experiments, this dual strategy disrupted mitochondrial function, increased reactive oxygen species, and suppressed heat-shock proteins that normally protect cancer cells from heat damage. The system also enabled real-time photoacoustic imaging. (ACS Applied Materials & Interfaces, 2026.)", "assessment": "This is an early-stage, in-vitro proof-of-concept study. The nanosystem is chemically creative and the rationale for combining H₂ with photothermal therapy is mechanistically plausible. However, all data come from cell-culture experiments — there are no animal or human data. Translation to clinical use requires substantial further development: demonstrating tumor targeting in living organisms, ruling out off-target toxicity, and solving the engineering challenge of delivering precisely controlled laser doses to deep tumors. This is not a human therapeutic proof and does not constitute evidence for H₂ therapy as a standalone treatment.", "abstract": "Conventional photothermal therapy (PTT) offers localized tumor ablation, yet its clinical impact is curtailed by heat shock protein (HSP)-mediated thermotolerance. Here, we introduce a conceptually new strategy that couples hydrogen gas therapy with PTT to overcome this intrinsic limitation. We engineered a multifunctional nanosystem, which was constructed from two-dimensional Ti3C2Tx nanosheets loaded with acid-responsive MgB2 prodrugs and further stabilized by polyethylene glycol, termed as MgB2-Ti3C2Tx@PEG. This nanosystem can hydrolyze to produce hydrogen gas and accelerate the reaction in a slightly acidic tumor microenvironment. Excited with an 808 nm laser, MgB2-Ti3C2Tx@PEG achieves a high photothermal conversion efficiency of 31.06%, while the generated heat can also simultaneously accelerate the hydrogen gas release. The liberated hydrogen gas then orchestrates a cascade of therapeutic effects; it triggers oxidative stress and a surge in reactive oxygen species within cancer cells, thus disrupting mitochondrial respiration function. Concurrently, the expression of HSPs is down-regulated, thereby eliminating thermotolerance and sensitizing tumor cells to PTT. This synergistic interplay ultimately results in robust tumor growth inhibition. Moreover, the strong near-infrared absorption and photoacoustic properties of Ti3C2Tx enable real-time imaging guidance, integrating therapy and diagnostics into a single nanoplatform. This work pioneers the use of hydrogen molecules to dismantle cellular defense mechanisms against hyperthermia, offering a paradigm shift toward more precise, potent, and intelligently guided PTT.", "conclusion": "Moreover, the strong near-infrared absorption and photoacoustic properties of Ti3C2Tx enable real-time imaging guidance, integrating therapy and diagnostics into a single nanoplatform. This work pioneers the use of hydrogen molecules to dismantle cellular defense mechanisms against hyperthermia, offering a paradigm shift toward more precise, potent, and intelligently guided PTT." }, { "pmid": "41702867", "year": 2026, "title": "Electrolyzed Hydrogen Water Improves Chemosensitivity to Anticancer Drugs by Potently Suppressing Autophagy.", "title_en": null, "title_de": "Elektrolysiertes Wasserstoffwasser verbessert die Chemosensitivität gegenüber Antikrebsmedikamenten durch starke Unterdrückung der Autophagie", "journal": "Journal of cellular and molecular medicine", "authors": "Yano et al.", "author_search": "yano yano", "doi": "10.1111/jcmm.71011", "doi_url": "https://doi.org/10.1111/jcmm.71011", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41702867/", "url": "https://h2medicine.org/studies/study-yano-2026-electrolyzed-improves-chemosensitivity-anticancer/", "methods": [ "drinking-hrw" ], "indications": [ "cancer", "fundamentals-safety" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2026 · Yano — Electrolyzed Hydrogen Water Improves Chemosensitivity to Anticancer Drugs by Potently Suppressing Autophagy", "summary": "Electrolyzed hydrogen water (EHW) suppressed autophagy — a recycling process cancer cells exploit to survive chemotherapy — and when combined with standard anticancer drugs (5-fluorouracil or paclitaxel), significantly reduced the viability of cervical and colorectal cancer cells in laboratory experiments. The mechanism involves activation of the mTORC1 signalling pathway, which normally inhibits autophagy. The authors propose EHW as a potentially safe adjuvant to existing chemotherapy protocols. (Journal of Cellular and Molecular Medicine, 2026.)", "assessment": "An in-vitro study with mechanistic novelty. The use of genome-wide RNA sequencing to identify the mTORC1 pathway adds scientific depth beyond simple cell-viability readouts. However, no animal models and no human data are presented. The safety claim in the conclusion is extrapolated from EHW's known low-risk profile, not from toxicology data in this paper. The combination of EHW and chemotherapy would require animal and then clinical trials before any therapeutic conclusions can be drawn. This is not evidence that hydrogen water improves chemotherapy outcomes in humans.", "abstract": "Autophagy is an intracellular recycling system that contributes to the maintenance of cellular homeostasis. However, by providing tolerance to various stressors, autophagy promotes the survival and proliferation of cancer cells and confers resistance to chemotherapy. Anticancer drugs activate autophagy, leading to drug resistance in cancer cells. Autophagy inhibitors, such as chloroquine and hydroxychloroquine, enhance the antitumor effects of anticancer drugs when used in combination with them. However, these inhibitors are associated with several adverse effects. Here, using genome-wide RNA sequencing analysis, we deciphered a novel function of electrolyzed hydrogen water (EHW) in suppressing autophagy by activating mammalian target of rapamycin complex 1 signalling. The combination of EHW with anticancer drugs, such as 5-fluorouracil or paclitaxel, which activate autophagy, significantly decreased the viability of cervical and colorectal cancer cells. Mechanistically, molecular hydrogen and trace elements in EHW may suppress autophagy and potentiate anticancer effects. Considering its safety, we propose that EHW can act as a novel adjuvant to anticancer therapy.", "conclusion": "Mechanistically, molecular hydrogen and trace elements in EHW may suppress autophagy and potentiate anticancer effects. Considering its safety, we propose that EHW can act as a novel adjuvant to anticancer therapy." }, { "pmid": "41697782", "year": 2026, "title": "Sub-nano molybdenum oxide nanorings as amplified atomic efficiency sonosensitizers for highly efficient sonodynamic tumor ablation.", "title_en": null, "title_de": "Sub-Nano-Molybdänoxid-Nanoringe als Sonosensibilisatoren mit verstärkter atomarer Effizienz für hocheffiziente sonodynamische Tumorablation", "journal": "Nanoscale", "authors": "Zhang et al.", "author_search": "zhang zhang", "doi": "10.1039/d5nr05289k", "doi_url": "https://doi.org/10.1039/d5nr05289k", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41697782/", "url": "https://h2medicine.org/studies/study-zhang-2026-sub-nano-molybdenum-oxide/", "methods": [ "unspecified" ], "indications": [ "cancer", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2026 · Zhang — Sub-nano Molybdenum Oxide Nanorings as Amplified Atomic Efficiency Sonosensitizers for Highly Efficient Sonodynamic Tumor Ablation", "summary": "Sub-nanometer molybdenum oxide nanorings (MoOx-S NRs) were designed as a dual-function nanosystem that generates both reactive oxygen species and hydrogen gas under ultrasound stimulation, aiming to kill cancer cells and modulate the tumor microenvironment. In cell culture and early laboratory experiments, the system produced cytotoxic singlet oxygen and superoxide radicals while hydrogen penetrated cell nuclei to reduce tumor-related inflammation. This is an in-vitro material-science study; no human evidence is presented. (Nanoscale, 2026.)", "assessment": "A materials-science, in-vitro study with no animal or human data. The catalytic chemistry is innovative and the combination of sonodynamic and hydrogen therapy is conceptually interesting. However, all results are from cell culture; the claim that hydrogen „penetrates the cell nucleus“ is a mechanistic proposal, not a directly measured outcome in this study. Sub-nanometer nanomaterial fabrication also raises translational challenges around batch reproducibility, biodegradation, and systemic toxicity that are not addressed here. This is not human evidence for any H₂-based cancer treatment.", "abstract": "Sub-nanometer structured molybdenum oxide nanorings (MoOx-S NRs) are designed as a dual-functional nano-sensitizer and single-atom nano-enzyme, used for ultrasound-enhanced hydrogen therapy. The unique sub-nanometer structure provides unsaturated coordination sites and sulfur groups, while its high surface energy generates delocalized electrons, thereby optimizing the activation energy and enhancing the tumor Russell-type catalytic therapy mediated by singlet oxygen under hypoxic conditions. Compared with traditional MoOx NPs, the MoOx-S NRs significantly increase the generation of reactive oxygen species and hydrogen triggered by ultrasound. Under ultrasound action, the MoOx-S NRs produce cytotoxic singlet oxygen and superoxide radicals, damage cancer cells and inhibit tumor growth. Moreover, the released hydrogen further penetrates the cell nucleus, regulating the tumor microenvironment and disrupting the inflammatory pathways to alleviate tumor-related inflammation. This work demonstrates an efficient strategy for using sub-nanometer MoOx-S NRs combined with the Russell-type catalytic and hydrogen therapy, providing a new perspective for cancer nanomedicine.", "conclusion": "Moreover, the released hydrogen further penetrates the cell nucleus, regulating the tumor microenvironment and disrupting the inflammatory pathways to alleviate tumor-related inflammation. This work demonstrates an efficient strategy for using sub-nanometer MoOx-S NRs combined with the Russell-type catalytic and hydrogen therapy, providing a new perspective for cancer nanomedicine." }, { "pmid": "41655909", "year": 2026, "title": "A hydrogen generator enhances immunogenic transarterial chemoembolization in hepatocellular carcinoma.", "title_en": null, "title_de": "Ein Wasserstoffgenerator verstärkt die immunogene transarterielle Chemoembolisation beim hepatozellulären Karzinom", "journal": "Journal of controlled release : official journal of the Controlled Release Society", "authors": "Cao et al.", "author_search": "cao cao", "doi": "10.1016/j.jconrel.2026.114694", "doi_url": "https://doi.org/10.1016/j.jconrel.2026.114694", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41655909/", "url": "https://h2medicine.org/studies/study-cao-2026-generator-enhances-immunogenic-transarterial/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "liver", "cardiovascular", "cancer", "immune-system" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2026 · Cao — A Hydrogen Generator Enhances Immunogenic Transarterial Chemoembolization in Hepatocellular Carcinoma", "summary": "Adding a hydrogen-releasing material (nano-CaH₂) to the standard TACE (transarterial chemoembolization) procedure for liver cancer enabled local H₂ release that reduced tumor hypoxia, enhanced drug effectiveness, and activated anti-tumor immune responses — all demonstrated in animal models. The hydrogen neutralized the acidic tumor microenvironment and boosted immunogenic cell death triggered by the chemotherapy drug epirubicin. (Journal of Controlled Release, 2026.)", "assessment": "A preclinical (animal model) study that makes a mechanistically coherent case for adding H₂ release to TACE. The multi-pronged rationale — hypoxia relief, acid neutralization, immunogenic cell death amplification — is well-supported conceptually. However, all efficacy data are from animal models; human pharmacokinetics, immune responses, and safety profile would differ. TACE itself is a highly specialized interventional procedure, and incorporating a novel nanomaterial carries additional regulatory and safety hurdles. This is not clinical evidence and should not be extrapolated to human therapy.", "abstract": "Conventional transarterial chemoembolization (TACE) regimens for hepatocellular carcinoma (HCC) are often compromised in efficacy due to hypoxia and acidosis within the tumor microenvironment (TME), frequently leading to unsatisfactory treatment outcomes and tumor recurrence. To overcome these limitations, this study introduces an innovative approach by incorporating a hydrogen generator (calcium hydride, CaH₂) into an epirubicin (EPI)-iodized oil embolization system. This design enables local hydrogen release to remodel the TME following TACE, thereby enhancing the combined chemo-immunotherapeutic antitumor response. Nano-CaH₂ particles, co-delivered locally via TACE, undergo hydrolysis to continuously release hydrogen gas (H₂) and calcium ions (Ca2+). This reaction disrupts mitochondrial function in cancer cells, reduces oxygen consumption, alleviates tumor hypoxia, and consequently counteracts chemoresistance. Simultaneously, EPI induces immunogenic cell death (ICD) in moribund tumor cells, activating the host's antitumor immune response. Additionally, the hydroxide ions generated from CaH₂ hydrolysis neutralize the acidic TME, alleviating immunosuppression and further amplifying the chemo-immunotherapeutic synergy mediated by TACE. This strategy presents a novel method to improve TACE efficacy and facilitate its integration with immunotherapy, demonstrating considerable potential for clinical translation.", "conclusion": "Additionally, the hydroxide ions generated from CaH₂ hydrolysis neutralize the acidic TME, alleviating immunosuppression and further amplifying the chemo-immunotherapeutic synergy mediated by TACE. This strategy presents a novel method to improve TACE efficacy and facilitate its integration with immunotherapy, demonstrating considerable potential for clinical translation." }, { "pmid": "41582106", "year": 2026, "title": "Hydrogen inhalation is associated with a transient rightward shift in prefrontal oxyhemoglobin asymmetry and autonomic modulation.", "title_en": null, "title_de": "Wasserstoff-Inhalation ist mit einer vorübergehenden rechtsgerichteten Verschiebung der präfrontalen Oxyhämoglobin-Asymmetrie und autonomer Modulation assoziiert", "journal": "Scientific reports", "authors": "Moriya et al.", "author_search": "moriya moriya", "doi": "10.1038/s41598-026-36599-8", "doi_url": "https://doi.org/10.1038/s41598-026-36599-8", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41582106/", "url": "https://h2medicine.org/studies/study-moriya-2026-inhalation-associated-transient-rightward/", "methods": [ "inhalation", "bath-topical" ], "indications": [ "liver", "sports-exercise", "neurology", "cardiovascular", "immune-system", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2025 · Moriya et al. — Hydrogen Inhalation Is Associated With a Transient Rightward Shift in Prefrontal Oxyhemoglobin Asymmetry and Autonomic Modulation", "summary": "A single 30-minute session of pure hydrogen gas inhalation (99.9 % H₂, 300 mL/min via nasal cannula) transiently increased oxygenation in the right prefrontal cortex and simultaneously altered heart-rate variability in healthy adults — findings consistent with a brief, coordinated neurovascular-autonomic response. Both effects normalised within 90 minutes of stopping inhalation. (Scientific Reports, 2025.)", "assessment": "A well-designed exploratory physiology study in healthy adults. Its value lies in documenting acute neurovascular and autonomic responses to H₂ inhalation — territory largely unexplored in humans. Limitations: small sample (n not specified in abstract), healthy volunteers only, high-concentration H₂ protocol (99.9 %) not representative of therapeutic use, no cognitive performance outcomes measured, unclear whether the right-PFC shift has any beneficial or adverse clinical meaning. The transient nature of all effects reinforces the need for repeated-dose or longer-exposure trials before drawing conclusions about cognitive or cardiovascular benefit.", "abstract": "Molecular hydrogen (H2) has selective antioxidant and anti-inflammatory properties, yet its immediate effects on human cerebral oxygenation and autonomic function remain unclear. In this study, we evaluated acute central and autonomic responses to a single 30-minute session of hydrogen inhalation in healthy adults, using 99.9% hydrogen delivered via nasal cannula at a fixed flow rate of 300 mL/min. Cerebral oxygenation was assessed using time-domain near-infrared spectroscopy (TD-NIRS) to quantify the concentrations of oxyhemoglobin (oxy-Hb) and deoxyhemoglobin (deoxy-Hb) in the bilateral prefrontal cortex (PFC), and to calculate interhemispheric asymmetry indices before hydrogen inhalation, immediately after the end of inhalation, and at 30 and 90 min thereafter. Autonomic activity was assessed via continuous electrocardiography (ECG) to derive heart rate, R-R interval, and frequency-domain heart rate variability metrics (low-frequency (LF), high-frequency (HF) and LF/HF ratio). Hydrogen inhalation elicited robust, transient increases in the right-PFC asymmetry of the oxy-Hb concentration. Concurrently, the LF/HF ratio increased during inhalation, indicating sympathetic activation, followed by decreases in the heart rate after inhalation, consistent with parasympathetic recovery. These parallel cerebral and autonomic responses suggest a coordinated neurovascular-autonomic coupling in response to hydrogen inhalation. Our findings show that acute hydrogen inhalation transiently modulates PFC oxygenation lateralization and autonomic tone, suggesting potential relevance to cognitive and cardiovascular regulation.", "conclusion": "These parallel cerebral and autonomic responses suggest a coordinated neurovascular-autonomic coupling in response to hydrogen inhalation. Our findings show that acute hydrogen inhalation transiently modulates PFC oxygenation lateralization and autonomic tone, suggesting potential relevance to cognitive and cardiovascular regulation." }, { "pmid": "41580925", "year": 2026, "title": "Synergistic Calcium Overload and Hydrogen Release Potentiate Robust Antitumor Immunity.", "title_en": null, "title_de": "Synergistische Calcium-Überladung und Wasserstofffreisetzung verstärken eine robuste Antitumor-Immunität", "journal": "Advanced healthcare materials", "authors": "Liang et al.", "author_search": "liang liang", "doi": "10.1002/adhm.202505332", "doi_url": "https://doi.org/10.1002/adhm.202505332", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41580925/", "url": "https://h2medicine.org/studies/study-liang-2026-synergistic-calcium-overload-release/", "methods": [ "inhalation" ], "indications": [ "liver", "cancer", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2026 · Liang — Synergistic Calcium Overload and Hydrogen Release Potentiate Robust Antitumor Immunity", "summary": "A nanoplatform called Ca@CMPN combines calcium hydride and curcumin to simultaneously flood cancer cells with calcium ions (triggering immunogenic cell death) and release H₂ to reduce oxidative stress and reshape the immunosuppressive tumor microenvironment. Both in-vitro and in-vivo (animal) studies showed enhanced tumor growth inhibition and a stronger immune response, including dendritic cell activation and cytotoxic T-cell recruitment. (Advanced Healthcare Materials, 2026.)", "assessment": "A preclinical study (in-vitro + animal models) with a sophisticated, multi-component rationale. The combination of calcium overload, curcumin amplification, and H₂ immunoadjuvancy is mechanistically layered and the animal data add weight beyond cell culture alone. However, no human clinical data exist, and the polydopamine carrier system would require extensive biocompatibility, pharmacokinetic, and manufacturing studies before clinical evaluation. The use of natural curcumin as a component is noteworthy but curcumin's poor bioavailability in vivo is a known translational challenge. This is not human therapeutic evidence.", "abstract": "Immunogenic cell death (ICD) induced by calcium overload holds great promise for reversing the immunosuppressive tumor microenvironment (TME) and improving cancer immunotherapy. However, achieving sustained calcium dysregulation remains a major challenge. Herein, we report a novel nanoplatform, termed Ca@CMPN, which co-delivers calcium hydride and curcumin using a mesoporous polydopamine carrier for synergistic ion-interference and gas immunotherapy. Upon encountering the acidic TME, Ca@CMPN disintegrates to release Ca2+, initiating intracellular calcium overload, and concurrently generates hydrogen gas (H2). Crucially, the co-released curcumin acts from within the cell, amplifying the calcium overload by disrupting organellar calcium homeostasis, thereby ensuring robust ICD. Meanwhile, H2 serves as a potent immunoadjuvant to alleviate oxidative stress and remodel the immunosuppressive TME. Both in vitro and in vivo studies demonstrate that Ca@CMPN effectively inhibits tumor growth and reprograms the TME, as evidenced by enhanced dendritic cell maturation, activation of cytotoxic T cells, and elevated levels of pro-inflammatory cytokines (interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α)). This work presents a paradigm-shifting strategy that synergizes ion-interference therapy with hydrogen immunotherapy, offering a powerful nanoplatform to unlock the full potential of cancer immunotherapy.", "conclusion": "Both in vitro and in vivo studies demonstrate that Ca@CMPN effectively inhibits tumor growth and reprograms the TME, as evidenced by enhanced dendritic cell maturation, activation of cytotoxic T cells, and elevated levels of pro-inflammatory cytokines (interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α)). This work presents a paradigm-shifting strategy that synergizes ion-interference therapy" }, { "pmid": "41533764", "year": 2026, "title": "Hydrogen ameliorates psoriasis-like skin inflammation via inhibiting the cGAS-STING pathway.", "title_en": null, "title_de": "Wasserstoff lindert psoriasisartige Hautentzündung durch Hemmung des cGAS-STING-Signalwegs", "journal": "Clinical and experimental immunology", "authors": "Wu et al.", "author_search": "wu wu", "doi": "10.1093/cei/uxaf081", "doi_url": "https://doi.org/10.1093/cei/uxaf081", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41533764/", "url": "https://h2medicine.org/studies/study-wu-2026-ameliorates-psoriasis-like-skin/", "methods": [ "drinking-hrw" ], "indications": [ "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2026 · Wu — Hydrogen Ameliorates Psoriasis-Like Skin Inflammation via Inhibiting the cGAS-STING Pathway", "summary": "In a mouse model of psoriasis, hydrogen-rich water significantly reduced skin inflammation by inhibiting the cGAS-STING signalling pathway — a key driver of the excessive immune activation characteristic of psoriasis. Hydrogen decreased markers of keratinocyte proliferation (Ki-67, BCL2, BAX) and reduced reactive oxygen species and inflammatory cytokines both in cell culture and in animals. (Clinical and Experimental Immunology, 2026.)", "assessment": "A preclinical (animal + in-vitro) study with a concrete mechanistic finding. Identifying cGAS-STING as the pathway targeted by H₂ in psoriasis is a meaningful scientific contribution that distinguishes this from generic „antioxidant“ explanations. However, the evidence is entirely from mouse models and cell culture. Human psoriasis involves complex immune dysregulation that is not fully replicated in imiquimod mouse models. Clinical trials in human psoriasis patients — which do not yet exist — would be required to establish whether H₂ has any clinically meaningful effect. This is not a human therapeutic proof.", "abstract": "Psoriasis is a chronic disease caused by abnormal immune system response, which is characterized by excessive keratinocyte proliferation and the activation of cytokine signaling pathways. In a previous study, we demonstrated in a psoriasis mouse model that hydrogen-rich water, an effective reactive oxygen species (ROS) scavenger, significantly improves disease severity. However, the precise molecular mechanism by which hydrogen helps in psoriasis treatment remains inadequately understood. This study assessed the role of hydrogen in suppressing keratinocyte hyperproliferation. We observed that the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon gene signaling was activated in psoriasis-like skin inflammation, which was dramatically inhibited by hydrogen treatment both in vitro and in vivo. Consistently, hydrogen decreased proliferative marker expression, including BCL2, BAX, and Ki-67, and significantly reduced ROS and inflammatory cytokines production. Our study suggests that molecular hydrogen could function as a potential treatment for psoriasis.", "conclusion": "Consistently, hydrogen decreased proliferative marker expression, including BCL2, BAX, and Ki-67, and significantly reduced ROS and inflammatory cytokines production. Our study suggests that molecular hydrogen could function as a potential treatment for psoriasis." }, { "pmid": "41482402", "year": 2026, "title": "Rhupus Syndrome With Multiple Drug Intolerances Managed by Reduced-dose Rituximab and Adjunctive Molecular Hydrogen Therapy: A Case Report.", "title_en": null, "title_de": "Rhupus-Syndrom mit multiplen Arzneimittelunverträglichkeiten, behandelt mit dosisreduziertem Rituximab und adjunktiver Therapie mit molekularem Wasserstoff: Ein Fallbericht", "journal": "In vivo (Athens, Greece)", "authors": "Tsai et al.", "author_search": "tsai tsai", "doi": "10.21873/invivo.14221", "doi_url": "https://doi.org/10.21873/invivo.14221", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41482402/", "url": "https://h2medicine.org/studies/study-tsai-2026-rhupus-syndrome-multiple-drug/", "methods": [ "drinking-hrw" ], "indications": [ "cardiovascular", "joints-rheumatology", "immune-system", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2026 · Tsai et al. — Rhupus Syndrome With Multiple Drug Intolerances Managed by Reduced-dose Rituximab and Adjunctive Molecular Hydrogen Therapy: A Case Report", "summary": "A 47-year-old man with the rare overlap of rheumatoid arthritis and systemic lupus erythematosus (Rhupus syndrome), who had failed or was intolerant to six different conventional drugs, achieved sustained disease control after adding oral molecular hydrogen capsules to low-dose rituximab — with normalisation of anti-dsDNA antibody, complement levels, and inflammatory markers, and successful discontinuation of prednisone. (In Vivo, 2026.)", "assessment": "Single case report — inherently limited in generalisability. The steroid withdrawal and immunological normalisation are clinically meaningful outcomes, but concurrent rituximab use makes causal attribution of any benefit to H₂ impossible. Notable strength: extensive and systematic immunophenotyping over time. Key limitations: n = 1, no placebo or control arm, temporal correlation ≠ causation, drug intolerances may themselves have influenced the disease course, avascular necrosis from prior corticosteroid use is a serious background comorbidity. Adds to a growing case-series signal from the same research group and warrants a prospective trial.", "abstract": "BACKGROUND/AIM: Rhupus syndrome, an overlap of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), is a rare condition characterized by heterogeneous clinical manifestations and difficult management. Conventional therapies, including glucocorticoids, disease-modifying anti-rheumatic drugs (DMARDs), immunosuppressants, and biologics, are often limited by drug intolerance and steroid-related complications. Molecular hydrogen (H2) has emerged as a potential adjuvant therapy due to its antioxidant and immunomodulatory properties. This report aimed to evaluate the clinical efficacy of H2 as an adjunct to rituximab in a patient with refractory Rhupus and multiple drug intolerances. CASE REPORT: We report a 47-year-old male with a 27-year history of rheumatoid arthritis, who subsequently developed systemic lupus erythematosus, fulfilling criteria for Rhupus syndrome. His disease course was complicated by multiple drug intolerances, including adverse reactions to methotrexate, sulfasalazine, hydroxychloroquine, azathioprine, leflunomide, and rituximab at standard dosing. Despite reduced-dose rituximab and mycophenolic acid, disease activity persisted and lupus nephritis was confirmed. In October 2023, oral molecular hydrogen capsule therapy was initiated as adjuvant treatment, resulting in significant clinical improvement, which was paralleled by characteristic changes in T- and B-cell subsets, normalization of anti-dsDNA antibody, erythrocyte sedimentation rate (ESR), and complement levels, and successful discontinuation of prednisone. Hydrogen therapy was well tolerated without major adverse effects. The patient developed avascular necrosis from prior corticosteroid use but recovered well after hip arthroplasty in January 2025. Disease control was sustained with mycophenolic acid and continued hydrogen therapy. CONCLUSION: This case suggests molecular hydrogen therapy as a potential adjuvant for refractory Rhupus with multiple drug intolerances, showing immune modulation, reduced inflammation, steroid withdrawal, and sustained control with low-dose rituximab. Further studies are needed to confirm its efficacy and standardize its use.", "conclusion": "This case suggests molecular hydrogen therapy as a potential adjuvant for refractory Rhupus with multiple drug intolerances, showing immune modulation, reduced inflammation, steroid withdrawal, and sustained control with low-dose rituximab. Further studies are needed to confirm its efficacy and standardize its use." }, { "pmid": "41482388", "year": 2026, "title": "Adjuvant Molecular Hydrogen Therapy in SLE-associated Pulmonary Arterial Hypertension: A Case Report on Immunomodulatory Effects on Regulatory and Effector Lymphocytes.", "title_en": null, "title_de": "Adjuvante Therapie mit molekularem Wasserstoff bei SLE-assoziierter pulmonalarterieller Hypertonie: Ein Fallbericht über immunmodulatorische Effekte auf regulatorische und Effektor-Lymphozyten", "journal": "In vivo (Athens, Greece)", "authors": "Liu et al.", "author_search": "liu liu", "doi": "10.21873/invivo.14220", "doi_url": "https://doi.org/10.21873/invivo.14220", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41482388/", "url": "https://h2medicine.org/studies/study-liu-2026-adjuvant-sle-associated-pulmonary/", "methods": [ "unspecified" ], "indications": [ "neurology", "cardiovascular", "respiratory", "immune-system", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2026 · Liu et al. — Adjuvant Molecular Hydrogen Therapy in SLE-associated Pulmonary Arterial Hypertension: A Case Report on Immunomodulatory Effects on Regulatory and Effector Lymphocytes", "summary": "A 42-year-old woman with systemic lupus erythematosus complicated by pulmonary arterial hypertension (a severe, progressive condition) received hydrogen capsule therapy, after which serial immunophenotyping showed dynamic suppression of memory B-cell populations and changes in PD1 and Fas markers — patterns interpreted as evidence of immune tolerance induction. (In Vivo, 2026.)", "assessment": "Single case report with detailed immunological documentation. The mechanistic data are the primary contribution — clinical benefit is described qualitatively without haemodynamic endpoints (e.g., pulmonary artery pressure). Limitations: n = 1, unspecified H₂ delivery method (listed as „unspecified“ in the study metadata), no control condition, no quantitative clinical outcomes for PAH severity, concurrent standard SLE therapy. Taken together with the companion report (41167678), this group's work provides a coherent mechanistic hypothesis for H₂ in autoimmune disease that deserves investigation in a formal trial.", "abstract": "BACKGROUND/AIM: Pulmonary arterial hypertension (PAH) is a significant and challenging complication for patients with systemic lupus erythematosus (SLE). It is thought to arise from immune dysregulation and vascular remodeling, ultimately leading to progressive right heart failure. Molecular hydrogen therapy, a selective antioxidant and anti-inflammatory agent, may modulate the immune responses seen in autoimmune diseases. This case report details the use of adjuvant hydrogen capsule therapy in a patient with SLE with PAH, suggesting its potential as a novel approach for this difficult clinical condition. CASE REPORT: A 42-year-old Taiwanese woman with SLE-PAH received hydrogen capsule therapy, during which serial immunophenotyping revealed dynamic changes in suppressive markers including programmed cell death protein 1 (PD1) and Fas cell surface death receptor (FAS), as well as regulatory T- and B-cell subsets. Notably, the populations of double negative and class-switched memory B-cells decreased during therapy, suggesting durable immune suppression. These results support the effect of hydrogen capsule therapy in achieving immune tolerance and inflammation modulation. CONCLUSION: This case study suggests that molecular hydrogen therapy may be a promising treatment for patients with SLE-PAH, particularly due to its immunomodulatory effects.", "conclusion": "This case study suggests that molecular hydrogen therapy may be a promising treatment for patients with SLE-PAH, particularly due to its immunomodulatory effects." }, { "pmid": "41420835", "year": 2026, "title": "Pearl-Like Bioinspired Coating Enables Regulation of Mg Degradation for Osteoporotic Bone Repair.", "title_en": null, "title_de": "Perlenartige bioinspirierte Beschichtung ermöglicht die Regulierung des Mg-Abbaus für die osteoporotische Knochenheilung", "journal": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)", "authors": "Zhang et al.", "author_search": "zhang zhang", "doi": "10.1002/advs.202521927", "doi_url": "https://doi.org/10.1002/advs.202521927", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41420835/", "url": "https://h2medicine.org/studies/study-zhang-2026-pearl-like-bioinspired-coating/", "methods": [ "inhalation" ], "indications": [ "cardiovascular", "joints-rheumatology", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2026 · Zhang — Pearl-Like Bioinspired Coating Enables Regulation of Mg Degradation for Osteoporotic Bone Repair", "summary": "A pearl-inspired multilayer coating for magnesium alloy bone implants was developed to precisely control the rate at which magnesium degrades in osteoporotic bone — specifically preventing premature hydrogen gas release, which can cause local tissue problems. In osteoporotic rat models, the coated implant improved bone integration, vascularization, and immune regulation compared to uncoated implants. (Advanced Science, 2026.)", "assessment": "This paper is primarily an implant engineering and materials science study. H₂ appears here as an unwanted side-product of magnesium degradation that the coating is designed to suppress — not as a therapeutic tool. The biomimetic coating concept is scientifically interesting and the osteoporotic rat data are encouraging. However, all evidence is preclinical (animal model); human bone implant performance, immune responses, and long-term biodegradation behaviour would need independent clinical evaluation. No human data are presented.", "abstract": "In osteoporotic bones, the stability of orthopedic implants is compromised, and excessive M1 macrophage polarization at the bone-implant interface disrupts bone-immune homeostasis, leading to implant loosening or failure. To address this, this study develops a bionic magnesium alloy internal fixation coating inspired by the \"brick-and-mortar\" structure of pearl, aiming to improve bone-implant integration and vascularization in osteoporotic conditions. The multifunctional coating consists of a calcium phosphate (Ca-P) \"brick\" layer, which serves as a mineralization template and corrosion barrier, and fibronectin-mimetic peptides (Fn-mimetic peptides) as the \"mortar\" to promote cell adhesion, regulate immune responses, and stimulate angiogenesis. This bionic multilayer structure not only alleviates oxidative stress in the osteoporotic microenvironment but also fosters immune regulation-osteogenesis coupling and improves the bone-vascular-immune microenvironment. It precisely controls the degradation rate of Mg alloys and enhances tissue repair. The CaP layer reduces rapid degradation and prevents hydrogen gas release and local alkalinization, whereas Fn-mimetic peptides enhance early bone integration and vascularization. The synergistic effect of the magnesium alloy implant and bionic coating significantly improved bone implant stability, regeneration, and vascularization, as demonstrated in osteoporotic rat models, offering a promising strategy for the design of bone repair materials under pathological conditions.", "conclusion": "The CaP layer reduces rapid degradation and prevents hydrogen gas release and local alkalinization, whereas Fn-mimetic peptides enhance early bone integration and vascularization. The synergistic effect of the magnesium alloy implant and bionic coating significantly improved bone implant stability, regeneration, and vascularization, as demonstrated in osteoporotic rat models, offering a promising " }, { "pmid": "41308938", "year": 2026, "title": "Therapeutic potential of magnesium diboride nanosheets in PAH-associated right heart failure: Integrated multi-omics analysis reveals ferroptosis suppression via LC3/ATG5/NCOA4/FTH1 pathway.", "title_en": null, "title_de": "Therapeutisches Potenzial von Magnesiumdiborid-Nanoblättern bei PAH-assoziierter Rechtsherzinsuffizienz: Integrierte Multi-Omics-Analyse zeigt Ferroptose-Unterdrückung über den LC3/ATG5/NCOA4/FTH1-Signalweg", "journal": "Free radical biology & medicine", "authors": "Jiao et al.", "author_search": "jiao jiao", "doi": "10.1016/j.freeradbiomed.2025.11.030", "doi_url": "https://doi.org/10.1016/j.freeradbiomed.2025.11.030", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41308938/", "url": "https://h2medicine.org/studies/study-jiao-2026-therapeutic-magnesium-diboride-nanosheets/", "methods": [ "unspecified" ], "indications": [ "liver", "cardiovascular", "respiratory", "immune-system", "oxidative-stress", "fundamentals-safety" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2026 · Jiao — Therapeutic Potential of Magnesium Diboride Nanosheets in PAH-Associated Right Heart Failure: Integrated Multi-Omics Analysis Reveals Ferroptosis Suppression via LC3/ATG5/NCOA4/FTH1 Pathway", "summary": "Magnesium diboride (MgB₂) nanosheets — which release H₂ upon contact with body fluids — were tested in an animal model of pulmonary arterial hypertension (PAH) and its resulting right heart failure. An integrated transcriptomic and proteomic analysis revealed that the H₂-releasing nanosheets suppressed a specific cell-death pathway (ferroptosis) through the LC3/ATG5/NCOA4/FTH1 signalling axis, offering a potential cardioprotective mechanism. This is a preclinical study with no human clinical data. (Free Radical Biology & Medicine, 2026.)", "assessment": "A mechanistically detailed preclinical study that is notable for using multi-omics to identify ferroptosis suppression as the cardiac protective mechanism of H₂-releasing nanosheets in PAH. The study is also commendably honest about the delivery barriers of H₂ therapy. However, all data are from animal models; the ferroptosis pathway and nanosheet pharmacokinetics would need to be validated in human cardiac tissue. The nanosheet formulation itself would require extensive safety, manufacturing, and delivery studies before clinical use. No human clinical evidence is presented.", "abstract": "Pulmonary arterial hypertension (PAH) is a progressive obstructive pulmonary vasculopathy characterized by pathological vascular remodeling driven by excessive cellular proliferation, apoptosis resistance, chronic inflammation, fibrotic deposition, and dysregulated vasoconstriction. As the disease advances, these vascular abnormalities culminate in right heart failure (RHF). The right ventricular (RV) initially undergoes compensatory hypertrophy but ultimately decompensates, manifesting as chamber dilation, impaired contractility, and progressive fibrosis. Despite the critical determinant role of RV functional reserve in patient survival and prognosis, but no clinically validated interventions directly address RV adaptation. Molecular hydrogen (H2), a biologically safe therapeutic agent with exceptional antioxidative, anti-inflammatory, anti-apoptotic properties and autophagic flux-modulating activities, has demonstrated organoprotective efficacy in cardiovascular and cerebrovascular disorders. Nevertheless, its therapeutic potential in mitigating PAH-induced RHF remains unexplored. Clinical translation is hindered by hydrogen's high explosivity and low bioavailability, necessitating the development of safer and more efficient delivery strategies. This study developed novel hydrogen-releasing magnesium diboride nanosheets (MBNs), and employs an integrated transcriptomic-proteomic approach to investigate the cardioprotective effects of MBNs against PAH-induced RHF and elucidate its underlying molecular targets and mechanisms of action.", "conclusion": "Clinical translation is hindered by hydrogen's high explosivity and low bioavailability, necessitating the development of safer and more efficient delivery strategies. This study developed novel hydrogen-releasing magnesium diboride nanosheets (MBNs), and employs an integrated transcriptomic-proteomic approach to investigate the cardioprotective effects of MBNs against PAH-induced RHF and elucidat" }, { "pmid": "41198323", "year": 2026, "title": "Synergistic stretching-annealing and salting-out enabling ultrastrong, ultratough anisotropic bacterial cellulose conductive hydrogels for bioelectric sensors.", "title_en": null, "title_de": "Synergistisches Strecken-Tempern und Aussalzen ermöglichen ultrastarke, ultrazähe anisotrope leitfähige Hydrogele aus bakterieller Cellulose für bioelektrische Sensoren", "journal": "Carbohydrate polymers", "authors": "Lei et al.", "author_search": "lei lei", "doi": "10.1016/j.carbpol.2025.124513", "doi_url": "https://doi.org/10.1016/j.carbpol.2025.124513", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41198323/", "url": "https://h2medicine.org/studies/study-lei-2026-synergistic-stretching-annealing-salting/", "methods": [ "unspecified" ], "indications": [ "sports-exercise", "cardiovascular" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2026 · Lei — Synergistic Stretching-Annealing and Salting-Out Enabling Ultrastrong, Ultratough Anisotropic Bacterial Cellulose Conductive Hydrogels for Bioelectric Sensors", "summary": "This materials science study presents a manufacturing process (stretching + annealing + salting-out) for making bacterial cellulose-based hydrogels with extreme mechanical strength and electrical conductivity, intended for wearable bioelectric sensors (ECG, EMG). Molecular hydrogen is mentioned only as a descriptor of the chemical bonding interactions that the process improves — it is not a therapeutic agent in this study. (Carbohydrate Polymers, 2026.)", "assessment": "This paper has no direct relevance to H₂ gas therapy or hydrogen medicine. The mention of „molecular hydrogen“ in the abstract refers to inter-molecular hydrogen bonding in polymer science — a routine chemistry term. The study is a strong piece of materials engineering about wearable biosensors. It is included here for completeness, but readers should be aware that no conclusions about H₂ therapeutic effects can be drawn from this paper.", "abstract": "Developing high-performance hydrogels that simultaneously exhibit biocompatibility, exceptional strength, toughness, conductivity, and antibacterial properties is crucial for meeting the stringent demands of bioelectric signal monitoring. Herein, we present an integrated approach for designing anisotropic bacterial cellulose (BC) hydrogels (PBA/K-a%) involving stretching the as-prepared polyvinyl alcohol (PVA)-BC-2-acrylamido-2-methylpropanesulfonic acid (AMPS) hydrogels (PBA) to various elongation ratios (a%), followed by air-drying during annealing to align the polymer chains, and finally immersed in potassium citrate (K3Cit) solutions to enhance the polymeric interactions via a synergistic stretching-annealing and salting-out (SSAS) strategy. This effective strategy improves molecular hydrogen and coordination interactions, enhances crystallinity, and induces the orientation of polymer chains and nanofibers along the stretching direction, significantly increasing the mechanical robustness of the hydrogels. Notably, the P10%B0.45%A10%/K-100 % hydrogel demonstrates ultrahigh mechanical strength of 45.32 MPa, high strain of 838 %, and ultrahigh toughness of 256.26 MJ/m3, as well as good conductivity with 13.3 mS/cm. The cooperative incorporation of PAMPS and K3Cit endows the hydrogel with good antibacterial capacity, establishing it as a unique and effective wearable sensor. Furthermore, the PBA/K-100 % hydrogel was successfully employed for the bioelectric signal monitoring of electrocardiograms (ECG) and electromyograms (EMG), thus demonstrating its potential applications in human-machine interactions and bioelectronics.", "conclusion": "The cooperative incorporation of PAMPS and K3Cit endows the hydrogel with good antibacterial capacity, establishing it as a unique and effective wearable sensor. Furthermore, the PBA/K-100 % hydrogel was successfully employed for the bioelectric signal monitoring of electrocardiograms (ECG) and electromyograms (EMG), thus demonstrating its potential applications in human-machine interactions and b" }, { "pmid": "40944582", "year": 2026, "title": "Tumor Microenvironment-Responsive Hydrogen-Generating Zn-Doped ReZIF-8 Nanoplatform for Enhanced Tumor Suppression.", "title_en": null, "title_de": "Tumormikroumgebungs-responsive wasserstofferzeugende Zn-dotierte ReZIF-8-Nanoplattform zur verstärkten Tumorunterdrückung", "journal": "Advanced healthcare materials", "authors": "Qin et al.", "author_search": "qin qin", "doi": "10.1002/adhm.202502489", "doi_url": "https://doi.org/10.1002/adhm.202502489", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40944582/", "url": "https://h2medicine.org/studies/study-qin-2026-tumor-microenvironment-responsive-generating/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "cancer", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2026 · Qin — Tumor Microenvironment-Responsive Hydrogen-Generating Zn-Doped ReZIF-8 Nanoplatform for Enhanced Tumor Suppression", "summary": "A zinc-doped metal-organic framework nanoparticle (ReZIF-8) was designed to generate H₂ inside cancer cells in response to the acidic tumor microenvironment, while simultaneously releasing zinc ions that further disrupt cancer cell redox balance — triggering immunogenic cell death and, in combination with anti-PD-1 checkpoint therapy, suppressing tumor growth in a melanoma mouse model. (Advanced Healthcare Materials, 2026.)", "assessment": "A preclinical study (in-vitro + melanoma mouse model) with a well-designed multi-mechanism rationale. The combination of intracellular H₂ generation, Zn²⁺ overload, immunogenic cell death, and anti-PD-1 synergy is conceptually layered. The animal survival and metastasis data add weight beyond cell culture. However, no human clinical data exist. The intratumoral administration route limits applicability to accessible tumors, and incorporating this nanoplatform into clinical practice would require extensive regulatory and manufacturing development. This is not human therapeutic evidence.", "abstract": "Hydrogen-based tumor therapy demonstrates therapeutic potential, while the efficacy remains limited by insufficient intracellular hydrogen generation, poorly controlled release kinetics, and inadequate immune response potentiation. To address these limitations, a partially reduced zinc-doped zeolitic imidazolate framework-8 (ReZIF-8) is developed, functioning as a dual-functional nanoplatform for both intracellular hydrogen generation and controlled Zn(II) ions (Zn2+) overload. The cationic surface charge of ReZIF-8 enhances cellular internalization, while its pH-responsive properties facilitate controlled intracellular hydrogen gas (H2) release. The accumulated H2 and Zn2+ overload act synergistically to disrupt redox homeostasis in tumor cells, inducing reactive oxygen species (ROS)-dependent immunogenic cell death (ICD). This ICD activation robustly stimulates innate immune responses and enhances antigen cross-presentation. Intratumoral administration of ReZIF-8 in a B16F10 melanoma mouse model elicits potent antitumor efficacy via intracellular H2-triggered terminal differentiation and cell cycle arrest. The therapeutic effect is further enhanced in combination with αPD-1 immune checkpoint blockade, resulting in extended survival and significant suppression of metastatic progression, highlighting its translational potential. The ReZIF-8-mediated H2-generating nanoplatform reprograms intratumoral redox balance to simultaneously induce ICD, amplify antitumor immunity, and drive terminal differentiation. This triple-pronged mechanism leverages synergistic modulation to achieve comprehensive tumor control.", "conclusion": "The ReZIF-8-mediated H2-generating nanoplatform reprograms intratumoral redox balance to simultaneously induce ICD, amplify antitumor immunity, and drive terminal differentiation. This triple-pronged mechanism leverages synergistic modulation to achieve comprehensive tumor control." }, { "pmid": "41382996", "year": 2025, "title": "[Mechanisms and protective strategies for astronaut skin injury in deep space environments].", "title_en": null, "title_de": "Mechanismen und Schutzstrategien für Hautverletzungen von Astronauten in Tiefraumumgebungen", "journal": "Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences", "authors": "Xie et al.", "author_search": "xie xie", "doi": "10.11817/j.issn.1672-7347.2025.250443", "doi_url": "https://doi.org/10.11817/j.issn.1672-7347.2025.250443", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41382996/", "url": "https://h2medicine.org/studies/study-xie-2025-mechanisms-protective-strategies-astronaut/", "methods": [ "unspecified" ], "indications": [ "cancer", "skin-aging", "immune-system", "oxidative-stress", "fundamentals-safety" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2025 · Xie — Mechanisms and Protective Strategies for Astronaut Skin Injury in Deep Space Environments", "summary": "This review summarises the current understanding of how deep space conditions — microgravity, ionising radiation, lunar dust, and microbiome disruption — damage astronaut skin, and what engineering and biomedical strategies are being developed to protect it. Hydrogen-rich shielding materials are mentioned as one component of multi-layer spacesuit design, not as a therapeutic agent. The paper calls for personalised, intelligent health monitoring systems for future deep space missions. (Journal of Central South University. Medical Sciences, 2025.)", "assessment": "This is a narrative review — a literature synthesis, not an experimental study or clinical trial. It provides useful context about skin health challenges in deep space, but no original data are presented and no conclusions about H₂ therapy efficacy can be drawn. The reference to hydrogen-rich materials is to radiation physics and spacesuit engineering, not to hydrogen medicine. The review is a useful map of a niche research area but should be interpreted as a field overview, not as evidence for any specific intervention.", "abstract": "With the continuous advancement of deep space exploration missions, maintaining astronaut skin health has become a critical medical issue affecting the safety and effectiveness of long-duration missions. Deep space environmental stressors, including microgravity, ionizing radiation, lunar dust exposure, and microbiome dysbiosis, can synergistically disrupt the skin barrier structure, leading to immune homeostasis imbalance and impaired wound healing. In recent years, research on skin protection in deep space has gradually evolved into a systematic \"multi-dimensional integrated protective\" framework. From the engineering protection perspective, optimization of multi-layer composite spacesuit structures, the use of hydrogen-rich and boron-containing shielding materials, as well as cabin temperature-humidity regulation and debris-resistant technologies, have greatly enhanced environmental defense capacity. From the biomedical protection perspective, functional hydrogels, antimicrobial dressings, and active compounds derived from traditional Chinese medicine have demonstrated remarkable potential in repairing the skin barrier, modulating immunity, and providing antioxidant defense. Meanwhile, the development of skin microecological interventions and wearable physiological monitoring systems has fostered a trend toward personalized health management. Future research should focus on elucidating the interactive mechanisms among the space environment, skin, and immune barrier, while exploring intelligent monitoring and nanotechnology-based protection strategies. Establishing a predictive and preventive skin health safeguarding system will provide comprehensive medical support for future deep space missions.", "conclusion": "Future research should focus on elucidating the interactive mechanisms among the space environment, skin, and immune barrier, while exploring intelligent monitoring and nanotechnology-based protection strategies. Establishing a predictive and preventive skin health safeguarding system will provide comprehensive medical support for future deep space missions." }, { "pmid": "41373725", "year": 2025, "title": "Exploring the Potential of Molecular Hydrogen in Different Heart Failure Models: A Review.", "title_en": null, "title_de": "Erkundung des Potenzials von molekularem Wasserstoff in verschiedenen Herzinsuffizienz-Modellen: Eine Übersichtsarbeit", "journal": "International journal of molecular sciences", "authors": "Kornieieva et al.", "author_search": "kornieieva kornieieva", "doi": "10.3390/ijms262311574", "doi_url": "https://doi.org/10.3390/ijms262311574", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41373725/", "url": "https://h2medicine.org/studies/study-kornieieva-2025-exploring-different-heart-failure/", "methods": [ "unspecified" ], "indications": [ "cardiovascular", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2025 · Kornieieva — Exploring the Potential of Molecular Hydrogen in Different Heart Failure Models: A Review", "summary": "This is the first systematic review summarising all published research on molecular hydrogen (H₂) as a potential treatment in different heart failure models. The available preclinical literature indicates that H₂ may mitigate heart failure by reducing oxidative stress, inflammation, cardiomyocyte death, and adverse cardiac remodelling — but authors stress that clinical feasibility and efficacy in humans have yet to be established. (International Journal of Molecular Sciences, 2025.)", "assessment": "A useful, timely review — and the first of its kind to map H₂ research across HF subtypes. The authors navigate the evidence responsibly: they summarise preclinical promise while explicitly acknowledging the complete absence of human clinical trial data. All evidence they review comes from animal models and cell culture — no human clinical data for H₂ in heart failure yet exist. The review is therefore a research roadmap rather than evidence for clinical use. Readers should not interpret this summary as proof that H₂ is effective or safe in human heart failure patients.", "abstract": "Heart failure (HF) is increasing in prevalence in many countries around the world. HF is a complex clinical syndrome characterized by the heart's inability to pump blood effectively, resulting in significant morbidity and mortality. After an initial cardiac event (e.g., myocardial infarction, valve dysfunction, hypertension, etc.), adaptive mechanisms are activated to preserve cardiac function. Sustained activation of these mechanisms leads to cellular and structural changes involving cardiac remodeling and hypertrophy. This ultimately leads to impaired cardiac contractility and reduced cardiac output, with a 5-year HF-associated mortality rate up to 75%. The current treatment strategies for HF are not sufficient to cover all the underlying complex mechanisms. It has been demonstrated that molecular hydrogen (H2) exerts cardioprotective effects via its antioxidant, anti-inflammatory, and anti-apoptotic action. The number of studies exploring beneficial effects of H2 in different HF models is increasing. This is the first review summarizing the knowledge in this field. The available literature indicates that H2 may be effective in mitigating different HF pathologies via regulating cardiac oxidative stress and inflammation, cardiomyocyte death, and mitochondrial function/cell metabolism, as well as cardiac remodeling, including hypertrophy and fibrosis. As this area of research is still in its infancy, the feasibility and efficiency of H2 treatment in different HF types need further investigation.", "conclusion": "The available literature indicates that H2 may be effective in mitigating different HF pathologies via regulating cardiac oxidative stress and inflammation, cardiomyocyte death, and mitochondrial function/cell metabolism, as well as cardiac remodeling, including hypertrophy and fibrosis. As this area of research is still in its infancy, the feasibility and efficiency of H2 treatment in different H" }, { "pmid": "41285129", "year": 2025, "title": "Innovations in peritoneal dialysis fluid: biocompatible formulations and expanded therapeutic applications.", "title_en": null, "title_de": "Innovationen bei Peritonealdialyse-Flüssigkeit: biokompatible Formulierungen und erweiterte therapeutische Anwendungen", "journal": "Renal failure", "authors": "Xu et al.", "author_search": "xu xu", "doi": "10.1080/0886022x.2025.2583626", "doi_url": "https://doi.org/10.1080/0886022x.2025.2583626", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41285129/", "url": "https://h2medicine.org/studies/study-xu-2025-innovations-peritoneal-dialysis-fluid/", "methods": [ "unspecified" ], "indications": [ "cardiovascular", "kidney-dialysis" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2025 · Xu — Innovations in peritoneal dialysis fluid: biocompatible formulations and expanded therapeutic applications", "summary": "Conventional peritoneal dialysis fluids cause peritoneal fibrosis and metabolic damage — new biocompatible formulations combining novel osmotic agents, advanced buffers, and molecular hydrogen aim to overcome these limitations. This review also explores the expanding role of peritoneal dialysis in refractory heart failure. (Renal Failure, 2025.)", "assessment": "This is a narrative review summarising the state of innovation in peritoneal dialysis fluid technology. Molecular hydrogen appears as one component in a broader multi-agent strategy and is not the central focus of the paper. No new experimental data are presented. Clinical evidence for the most novel agents — including H₂ as a PD additive — is sparse; the authors themselves call for accelerated clinical translation. The review is useful for understanding where H₂ research fits within a wider biomedical innovation landscape, but should not be read as proof of clinical efficacy for H₂ in dialysis patients.", "abstract": "Peritoneal dialysis (PD) is a critical renal replacement therapy for end-stage kidney disease. However, its adoption remains limited, partly due to peritoneal fibrosis and metabolic complications induced by conventional glucose-based peritoneal dialysis fluid (PDF), the primary complications in PD patients and the leading cause of technique failure. This review outlines three innovative approaches to overcome these limitations: (1) novel biocompatible osmotic agents (L-carnitine can improve the metabolism of the peritoneum, and hyperbranched polyglycerol provides sustained ultrafiltration with dual peritoneal/renal protection), (2) advanced biocompatible buffers (citrate and pyruvate), and (3) peritoneal protectants (glycosaminoglycans and molecular hydrogen) that collectively mitigate fibrosis while protecting membrane function. These developments indicate a future direction for biocompatible PDF: integrating dual or triple protective functions of \"osmotic agents + buffers + additives\" synergy-optimizing hybrid formulations and accelerating clinical translation. Furthermore, we explored the emerging role of PD in refractory heart failure, where specialized PDF and steady-concentration protocols enhanced ultrafiltration efficiency. These advances address volume overload in cardiorenal syndrome, expanding PD's therapeutic scope of PD to systemic conditions such as heart failure.", "conclusion": "Furthermore, we explored the emerging role of PD in refractory heart failure, where specialized PDF and steady-concentration protocols enhanced ultrafiltration efficiency. These advances address volume overload in cardiorenal syndrome, expanding PD's therapeutic scope of PD to systemic conditions such as heart failure." }, { "pmid": "41194243", "year": 2025, "title": "Molecular mechanisms associated with effects of hydrogen molecule in liver diseases: the review of current evidence.", "title_en": null, "title_de": "Molekulare Mechanismen im Zusammenhang mit den Wirkungen des Wasserstoffmoleküls bei Lebererkrankungen: eine Übersicht der aktuellen Evidenz", "journal": "European journal of medical research", "authors": "Zhu et al.", "author_search": "zhu zhu", "doi": "10.1186/s40001-025-03347-z", "doi_url": "https://doi.org/10.1186/s40001-025-03347-z", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41194243/", "url": "https://h2medicine.org/studies/study-zhu-2025-mechanisms-associated-molecule-liver/", "methods": [ "unspecified" ], "indications": [ "metabolic", "liver", "cancer", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2025 · Zhu — Molecular mechanisms associated with effects of hydrogen molecule in liver diseases: the review of current evidence", "summary": "Oxidative stress and inflammation drive liver disease progression from inflammation to fibrosis and cancer — this review summarises how molecular hydrogen selectively neutralises harmful free radicals and modulates inflammatory signalling to potentially slow this cascade. Both animal studies and early clinical trials in chronic liver conditions are covered. (European Journal of Medical Research, 2025.)", "assessment": "This is a literature review, not a clinical trial. It synthesises existing animal and early clinical data and does not generate new evidence. The authors' conclusion that H₂ has „therapeutic potential” is supported by preclinical findings and a limited number of clinical observations, but standardised human trials in liver disease are still lacking. The review is scientifically balanced — it identifies open mechanistic questions and explicitly calls for more rigorous research. Readers should not interpret the presented findings as confirmed clinical efficacy.", "abstract": "Oxidative stress and inflammation play a key role in the occurrence and progression of liver diseases, inducing hepatocyte apoptosis, fibrosis, and even cancer. However, there is a lack of effective therapeutic interventions to slow liver inflammation and the progression of metabolic liver diseases. The unique biological properties of molecular hydrogen's selective scavenging of pathological free radicals have shown therapeutic potential in animal studies and clinical trials of chronic liver diseases. This review describes innovative technologies and applications of molecular hydrogen in the treatment of liver injury and liver metabolic diseases, focusing on its mechanisms of action in regulating redox and inflammatory cascade signal transduction and specifically discussing its potential for glucolipid metabolic homeostasis and intestinal microbiota remodeling, as well as cell protection. Future studies are needed to further identify the unknown mechanisms by which molecular hydrogen improves the beneficial role of the liver microenvironment and advance the clinical application of hydrogen therapy.", "conclusion": "This review describes innovative technologies and applications of molecular hydrogen in the treatment of liver injury and liver metabolic diseases, focusing on its mechanisms of action in regulating redox and inflammatory cascade signal transduction and specifically discussing its potential for glucolipid metabolic homeostasis and intestinal microbiota remodeling, as well as cell protection. Futur" }, { "pmid": "40619605", "year": 2025, "title": "Delivery of Molecular Hydrogen for Precision Immunomodulation: Mechanisms, Detection Methods, and Applications.", "title_en": null, "title_de": "Verabreichung von molekularem Wasserstoff zur präzisen Immunmodulation: Mechanismen, Nachweismethoden und Anwendungen", "journal": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)", "authors": "Li et al.", "author_search": "li li", "doi": "10.1002/advs.202500283", "doi_url": "https://doi.org/10.1002/advs.202500283", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40619605/", "url": "https://h2medicine.org/studies/study-li-2025-delivery-precision-immunomodulation-mechanisms/", "methods": [ "unspecified" ], "indications": [ "liver", "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2025 · Li — Delivery of Molecular Hydrogen for Precision Immunomodulation: Mechanisms, Detection Methods, and Applications", "summary": "Molecular hydrogen modulates immune function through antioxidant action, suppression of inflammatory mediators, and inhibition of apoptosis — yet the precise dose-efficacy relationship in living organisms remains unclear due to the lack of accurate in-vivo detection methods. This review surveys both the mechanisms and the current portfolio of H₂ delivery systems, identifying critical gaps that need to be filled before clinical precision use is possible. (Advanced Science, 2025.)", "assessment": "This is a scientific review that makes a genuinely useful contribution by explicitly flagging what is not yet known — particularly the absence of reliable in-vivo dosimetry and the incomplete mechanistic picture of H₂-mediated immunomodulation. No new experimental data are presented. The scope is broad (nanomaterials, inhalation systems, biological mechanisms) but the honest framing of unresolved issues makes this a credible starting point for researchers, not a clinical recommendation document. The findings are largely based on preclinical and in-vitro evidence; human immunomodulation data are limited.", "abstract": "The delivery of molecular hydrogen (H2) is increasingly recognized for its potential in precision immunomodulation, primarily through multiple pathways such as antioxidant action, modulation of inflammatory factors, and inhibition of apoptosis. These effects contribute to a balanced and functional immune system, highlighting the therapeutic promise of H2 in various inflammatory conditions. However, two critical issues remain unresolved: the unclear mechanism underlying the immunomodulatory effects of H2 and the lack of precision detection methods to clarify the dose-efficacy relationship in vivo. Since previous reviews focused on developing nanomaterials for H2 delivery, they often overlook analyses of the immunomodulation mechanisms and fail to update the detection methods. To address these gaps, a review that explores the immunomodulatory mechanisms of H2 is proposed, the recent detection methods, and the classification and applications of advanced H2 delivery systems, aiming to enhance the understanding of precision immunomodulation strategies leveraging their properties.", "conclusion": "Since previous reviews focused on developing nanomaterials for H2 delivery, they often overlook analyses of the immunomodulation mechanisms and fail to update the detection methods. To address these gaps, a review that explores the immunomodulatory mechanisms of H2 is proposed, the recent detection methods, and the classification and applications of advanced H2 delivery systems, aiming to enhance " }, { "pmid": "40569354", "year": 2025, "title": "Molecular hydrogen as a novel regulator of cellular pyroptosis: mechanistic insights and therapeutic implications.", "title_en": null, "title_de": "Molekularer Wasserstoff als neuartiger Regulator der zellulären Pyroptose: mechanistische Einblicke und therapeutische Implikationen", "journal": "Molecular biology reports", "authors": "Ye et al.", "author_search": "ye ye", "doi": "10.1007/s11033-025-10757-z", "doi_url": "https://doi.org/10.1007/s11033-025-10757-z", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40569354/", "url": "https://h2medicine.org/studies/study-ye-2025-regulator-cellular-pyroptosis-mechanistic/", "methods": [ "drinking-hrw" ], "indications": [ "liver", "neurology", "cancer", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2025 · Ye — Molecular hydrogen as a novel regulator of cellular pyroptosis: mechanistic insights and therapeutic implications", "summary": "Pyroptosis — a highly inflammatory form of programmed cell death — drives tissue damage in heart attacks, neurodegeneration, metabolic disease, and cancer; this review demonstrates that molecular hydrogen can regulate pyroptosis through multiple interconnected pathways, producing context-dependent protective or tumour-fighting effects. The field remains largely preclinical, with significant challenges still ahead before clinical use is feasible. (Molecular Biology Reports, 2025.)", "assessment": "This is a preclinical review — virtually all cited evidence comes from animal or cell-culture experiments. The mechanistic framework proposed (gasdermin redox modification, inflammasome disruption) is scientifically plausible but not yet validated in humans. The claimed tumour-selective pro-pyroptotic activity is particularly intriguing but also particularly in need of rigorous confirmation. These findings cannot be directly extrapolated to human therapy. The review is scientifically rigorous in framing limitations, making it a valuable reference for researchers, not a basis for therapeutic recommendations.", "abstract": "Pyroptosis, a highly inflammatory programmed cell death pathway, drives pathogenesis in numerous diseases through gasdermin-mediated membrane pore formation and massive cytokine release. While conventional anti-inflammatory therapies show limited efficacy, hydrogen emerges as a novel therapeutic agent with unique pyroptosis-regulatory capabilities. This review establishes a comprehensive mechanistic framework demonstrating that hydrogen modulates pyroptosis through interconnected pathways including direct gasdermin redox modification, mitochondrial signaling integration, and inflammasome assembly disruption. Systematic analysis across diverse disease models-cardiac ischemia-reperfusion, neuroinflammation, metabolic dysfunction, and cancer-reveals hydrogen's remarkable context-dependent effects: cytoprotective in normal tissues while promoting therapeutic pyroptosis in malignant cells. Hydrogen's regulatory mechanisms exhibit striking tissue specificity and temporal complexity, with immediate antioxidant effects transitioning to sustained anti-inflammatory responses. Despite compelling preclinical evidence demonstrating efficacy in myocardial injury, neurodegeneration, and systemic inflammation, significant translational barriers remain including delivery optimization, dosimetric standardization, and biomarker development. This review critically evaluates hydrogen's transformative therapeutic potential while addressing realistic implementation challenges, providing a roadmap for advancing this innovative paradigm from bench to bedside.", "conclusion": "Despite compelling preclinical evidence demonstrating efficacy in myocardial injury, neurodegeneration, and systemic inflammation, significant translational barriers remain including delivery optimization, dosimetric standardization, and biomarker development. This review critically evaluates hydrogen's transformative therapeutic potential while addressing realistic implementation challenges, prov" }, { "pmid": "40518021", "year": 2025, "title": "Molecular hydrogen therapy: A \"democratic\" emerging strategy against aging and age-related diseases.", "title_en": null, "title_de": "Therapie mit molekularem Wasserstoff: Eine „demokratische” aufkommende Strategie gegen Alterung und altersbedingte Erkrankungen", "journal": "Ageing research reviews", "authors": "Brandi et al.", "author_search": "brandi brandi", "doi": "10.1016/j.arr.2025.102802", "doi_url": "https://doi.org/10.1016/j.arr.2025.102802", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40518021/", "url": "https://h2medicine.org/studies/study-brandi-2025-democratic-emerging-strategy-against/", "methods": [ "unspecified" ], "indications": [ "neurology", "cardiovascular", "cancer", "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2025 · Brandi — Molecular hydrogen therapy: A „democratic” emerging strategy against aging and age-related diseases", "summary": "Aging is the primary risk factor for cardiovascular disease, neurodegeneration, metabolic conditions, and cancer — this review proposes that molecular hydrogen, owing to its antioxidant, anti-inflammatory, and senescence-regulating properties, may offer a widely accessible strategy for slowing age-related processes. The authors call the potential „democratic” due to H₂'s low cost, lack of toxicity, and pleiotropic activity, while acknowledging that the evidence base is still limited. (Ageing Research Reviews, 2025.)", "assessment": "This is a narrative review covering a broad and heterogeneous literature. It makes a useful conceptual argument that H₂'s known properties align with multiple aging hallmarks, but the available human data on aging-specific endpoints are limited. Most cited evidence is from animal or cell models. The „democratic” framing is engaging but should not obscure the early stage of the evidence base. The review is appropriately cautious in its wording and does not overstate clinical applicability. It is best read as a conceptual orientation paper, not as confirmation of anti-aging efficacy in humans.", "abstract": "Aging represents the main risk factor for the development of several diseases, including cardiovascular and metabolic conditions, neurodegenerative disorders and cancer. As the number of elderly people is increasing worldwide, different strategies to counteract age-related diseases have been investigated. Recently, the use of molecular hydrogen (H2) as a preventive and therapeutic approach has been proposed due to its antioxidant and anti-inflammatory properties, its ability to regulate cell senescence and death, and to restore intestinal eubiosis. Although the studies investigating the role of H2 in slowing-down aging and age-related diseases are still limited, current findings support the idea that its administration may be able to affect different hallmarks of these processes. The \"democratic\" characteristics of H2 rely on its potential widespread use due to its pleiotropic activity, the lack of toxicities and low costs. In this review we provide a comprehensive state of the art on current knowledge on the molecular and clinical features of aging and age-related diseases. Current therapeutic approaches to slow down these processes will be also discussed, with a main focus on the potential use of H2 as an innovative preventive and therapeutic strategy.", "conclusion": "In this review we provide a comprehensive state of the art on current knowledge on the molecular and clinical features of aging and age-related diseases. Current therapeutic approaches to slow down these processes will be also discussed, with a main focus on the potential use of H2 as an innovative preventive and therapeutic strategy." }, { "pmid": "40362357", "year": 2025, "title": "Molecular Hydrogen in the Treatment of Respiratory Diseases.", "title_en": null, "title_de": "Molekularer Wasserstoff bei der Behandlung von Atemwegserkrankungen", "journal": "International journal of molecular sciences", "authors": "Zajac et al.", "author_search": "zajac zajac", "doi": "10.3390/ijms26094116", "doi_url": "https://doi.org/10.3390/ijms26094116", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40362357/", "url": "https://h2medicine.org/studies/study-zajac-2025-respiratory-diseases/", "methods": [ "unspecified" ], "indications": [ "sports-exercise", "cancer", "respiratory", "immune-system", "allergy", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2025 · Zajac — Molecular Hydrogen in the Treatment of Respiratory Diseases", "summary": "This review compiles twenty years of research on molecular hydrogen in respiratory medicine, covering allergies, asthma, COPD, pulmonary fibrosis, lung injury, respiratory infections, and lung cancer. H₂'s antioxidant, anti-inflammatory, and anti-apoptotic mechanisms are mapped against each condition; most evidence remains preclinical. (International Journal of Molecular Sciences, 2025.)", "assessment": "This is a narrative literature review, not a meta-analysis or clinical trial. It provides a useful map of the H₂ respiratory research landscape across twenty years but does not pool effect sizes or apply formal quality assessment to individual studies. The evidence base is overwhelmingly preclinical (animal models, cell lines), with limited human trial data, particularly for chronic conditions. No single respiratory indication has yet accumulated sufficient clinical trial evidence to support H₂ as a standard treatment. The review serves as a research orientation tool, not a basis for clinical recommendations.", "abstract": "Molecular hydrogen is gaining increasing attention as an antioxidant, anti-inflammatory, and antiapoptotic agent. Once considered an inert gas, it reveals current therapeutic potential among others in inflammatory diseases, cancer, and sports medicine, among others. The present review aims to provide a consistent summary of the findings of the last twenty years on the use of molecular hydrogen in major respiratory diseases, including allergies, asthma, COPD, pulmonary fibrosis, lung injury of various origins, as well as cancer and infections of the respiratory tract. In addition, the basic mechanisms through which molecular hydrogen exercises its biological activity on the respiratory system are described.", "conclusion": "The present review aims to provide a consistent summary of the findings of the last twenty years on the use of molecular hydrogen in major respiratory diseases, including allergies, asthma, COPD, pulmonary fibrosis, lung injury of various origins, as well as cancer and infections of the respiratory tract. In addition, the basic mechanisms through which molecular hydrogen exercises its biological a" }, { "pmid": "40289982", "year": 2025, "title": "Advanced Glycation End Products and Skin Autoimmune Disorders: Pathogenic Insights into Vitiligo, Bullous Pemphigoid, and Type 1 Diabetes Mellitus.", "title_en": null, "title_de": "Advanced Glycation End Products und autoimmune Hauterkrankungen: Pathogenetische Einblicke in Vitiligo, bullöses Pemphigoid und Diabetes mellitus Typ 1", "journal": "Current medicinal chemistry", "authors": "Bjørklund et al.", "author_search": "bjørklund bjørklund", "doi": "10.2174/0109298673374335250410074811", "doi_url": "https://doi.org/10.2174/0109298673374335250410074811", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40289982/", "url": "https://h2medicine.org/studies/study-bjrklund-2025-advanced-glycation-end-products/", "methods": [ "drinking-hrw" ], "indications": [ "diabetes", "metabolic", "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2025 · Bjørklund — Advanced Glycation End Products and Skin Autoimmune Disorders: Pathogenic Insights into Vitiligo, Bullous Pemphigoid, and Type 1 Diabetes Mellitus", "summary": "Advanced glycation end products (AGEs) — toxic compounds formed under high blood sugar — trigger oxidative stress and autoimmune responses that can cause skin diseases such as vitiligo and bullous pemphigoid in Type 1 Diabetes. This review evaluates therapeutic strategies targeting AGE formation and oxidative stress, including hydrogen-rich water as an antioxidant adjunct. (Current Medicinal Chemistry, 2025.)", "assessment": "This is a mechanistic review exploring the AGE-RAGE-autoimmunity axis in the context of Type 1 Diabetes-associated skin disorders. Hydrogen-rich water is mentioned briefly as one antioxidant option among several — this is not an H₂-focused paper, and there are no clinical trials of H₂ specifically in vitiligo or bullous pemphigoid cited. The mechanistic framework is plausible and well-cited, but clinical evidence for any of the proposed therapies in these specific conditions is sparse. Findings are not directly transferable to treatment recommendations.", "abstract": "AGEs are molecules formed by nonenzymatic glycation of proteins, lipids, and nucleic acids, a process accelerated under hyperglycemic conditions such as DM1. These molecules interact with specific receptors, particularly the Receptor for AGEs (RAGE), triggering intracellular signaling cascades that promote oxidative stress through the generation of Reactive Oxygen Species (ROS) and activation of inflammatory pathways. A critical pathological mechanism involves the formation of neoantigens, modified self-proteins that elicit immune responses. Structural alterations caused by AGEs expose new epitopes or modify existing ones, making them targets for autoreactive T cells and autoantibodies. This mechanism is implicated in autoimmune skin diseases such as vitiligo and bullous pemphigoid. Oxidative stress plays a central role in these diseases, exacerbated by AGEs through the generation of ROS and depletion of antioxidants, leading to melanocyte destruction in vitiligo and tissue damage in bullous pemphigoid. In addition, hypoxia enhances ROS production, mitochondria, and other cellular systems contributing to oxidative stress. Emerging evidence suggests that hypoxia can be mitigated by oxygen nanobubbles. Targeting AGE formation and oxidative stress presents a promising approach for the management of autoimmune skin disorders in DM1. Therapeutic strategies targeting AGE formation, oxidative stress, and immune dysregulation show promise for managing autoimmune skin disorders in Type 1 Diabetes Mellitus (T1DM). AGE inhibitors, such as aminoguanidine and pyridoxamine, reduce non-enzymatic protein glycation, limiting AGE accumulation and inflammatory signaling. Antioxidants, including polyphenols, vitamins C and E, N-acetylcysteine, selenium, and hydrogen-rich water, help neutralize Reactive Oxygen Species (ROS), restoring oxidative balance. Combining AGE inhibitors and antioxidants may provide synergistic benefits by reducing oxidative stress and protein immunogenicity. Additionally, immune modulation therapies, such as Treg therapy and cytokine inhibitors, aim to restore immune tolerance and prevent autoimmune activation. Anti-TNF-α and IL-6 inhibitors offer targeted inflammation suppression, while RAGE antagonists mitigate AGE-induced immune dysregulation. This study aims to explore the role of Advanced Glycation End products (AGEs) in the pathogenesis of autoimmune skin disorders associated with type 1 Diabetes Mellitus (DM1) and to evaluate potential therapeutic strategies targeting AGE formation and oxidative stress.", "conclusion": "Anti-TNF-α and IL-6 inhibitors offer targeted inflammation suppression, while RAGE antagonists mitigate AGE-induced immune dysregulation. This study aims to explore the role of Advanced Glycation End products (AGEs) in the pathogenesis of autoimmune skin disorders associated with type 1 Diabetes Mellitus (DM1) and to evaluate potential therapeutic strategies targeting AGE formation and oxidative s" }, { "pmid": "40243461", "year": 2025, "title": "Antioxidant Therapies as Emerging Adjuncts in Rheumatoid Arthritis: Targeting Oxidative Stress to Enhance Treatment Outcomes.", "title_en": null, "title_de": "Antioxidative Therapien als aufkommende adjunktive Behandlungen bei rheumatoider Arthritis: Oxidativer Stress als Zielstruktur zur Verbesserung der Behandlungsergebnisse", "journal": "International journal of molecular sciences", "authors": "Bilski et al.", "author_search": "bilski bilski", "doi": "10.3390/ijms26072873", "doi_url": "https://doi.org/10.3390/ijms26072873", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40243461/", "url": "https://h2medicine.org/studies/study-bilski-2025-antioxidant-therapies-emerging-adjuncts/", "methods": [ "drinking-hrw" ], "indications": [ "joints-rheumatology", "immune-system", "oxidative-stress", "fundamentals-safety" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2025 · Bilski — Antioxidant Therapies as Emerging Adjuncts in Rheumatoid Arthritis: Targeting Oxidative Stress to Enhance Treatment Outcomes", "summary": "Rheumatoid arthritis is driven not only by immune dysregulation but also by oxidative stress — current DMARDs fail to address ROS-mediated joint damage, opening space for antioxidant adjuncts. This review covers molecular hydrogen alongside curcumin, resveratrol, NAC, and vitamins as candidate add-on strategies, with a frank assessment that further clinical trials are needed. (International Journal of Molecular Sciences, 2025.)", "assessment": "This is a narrative review, not a clinical trial or meta-analysis. It makes a scientifically coherent case for H₂ as a potential antioxidant adjunct in RA based on its mechanism of action, but the clinical evidence base in rheumatoid arthritis specifically is very thin. The review covers multiple compounds simultaneously, which limits depth for any single agent. The authors' explicit call for clinical trials underscores that this remains an investigational concept. Current findings should not be interpreted as evidence of efficacy in RA patients.", "abstract": "Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent inflammation and progressive joint destruction. Recent data underscore oxidative stress as a primary factor in the pathophysiology of rheumatoid arthritis, intensifying inflammatory processes and tissue damage via the overproduction of reactive oxygen species (ROS) and compromised antioxidant defenses. Current therapies, including disease-modifying antirheumatic drugs (DMARDs), primarily target immune dysregulation but fail to address oxidative stress, necessitating novel adjunctive treatment strategies. This review explores the potential of antioxidant-based therapies as complementary approaches to RA management. Natural compounds such as curcumin, resveratrol, sulforaphane, and propolis exhibit strong anti-inflammatory and antioxidative properties by modulating redox-sensitive pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase (HO-1). N-acetylcysteine (NAC) replenishes intracellular glutathione, enhancing cellular resilience against oxidative stress. Additionally, molecular hydrogen (H2) selectively neutralizes harmful ROS, reducing oxidative damage and inflammation. The role of vitamin supplementation (D, B12, C, and K) in regulating immune responses and protecting joint structures is also discussed. This review aims to evaluate the efficacy and potential clinical applications of antioxidant therapies in RA, emphasizing their role in mitigating oxidative damage and improving treatment outcomes. While preliminary findings are promising, further clinical trials are needed to establish standardized dosing, long-term safety, and their integration into current RA treatment protocols.", "conclusion": "This review aims to evaluate the efficacy and potential clinical applications of antioxidant therapies in RA, emphasizing their role in mitigating oxidative damage and improving treatment outcomes. While preliminary findings are promising, further clinical trials are needed to establish standardized dosing, long-term safety, and their integration into current RA treatment protocols." }, { "pmid": "40088576", "year": 2025, "title": "Activation, interaction and intimation of Nrf2 pathway and their mutational studies causing Nrf2 associated cancer.", "title_en": null, "title_de": "Aktivierung, Interaktion und Signalvermittlung des Nrf2-Signalwegs und ihre Mutationsstudien als Ursache Nrf2-assoziierter Krebserkrankungen", "journal": "Biochimica et biophysica acta. Molecular basis of disease", "authors": "Sahu et al.", "author_search": "sahu sahu", "doi": "10.1016/j.bbadis.2025.167764", "doi_url": "https://doi.org/10.1016/j.bbadis.2025.167764", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40088576/", "url": "https://h2medicine.org/studies/study-sahu-2025-activation-interaction-intimation-nrf2/", "methods": [ "unspecified" ], "indications": [ "cancer", "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2025 · Sahu — Activation, interaction and intimation of Nrf2 pathway and their mutational studies causing Nrf2 associated cancer", "summary": "The Nrf2 transcription factor is the cell's master antioxidant switch — when Nrf2 functions correctly, it defends against cancer-driving oxidative damage; when mutated, it can paradoxically protect tumour cells from therapy. This review explains how molecular hydrogen activates the Nrf2 pathway and where this dual role creates both opportunities and complications for cancer biology. (Biochimica et Biophysica Acta — Molecular Basis of Disease, 2025.)", "assessment": "This is a mechanistic review on Nrf2 biology, mutations, and cancer — H₂ appears as one Nrf2-activating agent among many discussed. The proposed mechanism (iron porphyrin oxidation → Keap1 cysteine interaction) is based on in-vitro and computational data and has not been confirmed in human studies. Importantly, Nrf2's dual role — tumour suppressor in normal cells, tumour promoter in constitutively-active mutant cancers — means that broad Nrf2 activation is not without risk in oncological contexts. This nuance is implied by the paper's focus on cancer-promoting Nrf2 mutations but could be stated more explicitly. Readers interested specifically in H₂ should treat the mechanistic claims as hypothesis-generating, not established.", "abstract": "Responses against infection trigger several signaling pathways that lead to the production of cytokines, these cytokines release ROS and RNS, damaging DNA and proteins turn into various diseases including cancer. To combat these harmful cytokines, the Nrf2 pathway is activated. The gene NFE2L2 encodes Nrf2, which is divided into seven conserved domains (Neh1-7). The DLG and ETGE motifs, conserved sequences of amino acid in the Neh2 domain of Nrf2, bind to the BTB domain of Keap1. BTB domain promotes Keap1's homodimerization resulting in Cul3 recruitment providing scaffold formation to E2 ubiquitin ligase to form ubiquitin complex. Under normal conditions, this complex regularly degrades Nrf2. However, once the cell is exposed to oxidative stress by ROS interaction with Keap1 resulting in conformational changes that stabilize the Nrf2. Nrf2 further concentrates on the nucleus where it binds with the transcriptional factor to perform the desired genes transcription for synthesizing SOD, GSH, CAT, and various other proteins which reduce the ROS levels preventing certain diseases. To prevent cells from oxidative stress, molecular hydrogen activates the Nrf2 pathway. To activate the Nrf2 pathway, molecular hydrogen oxidizes the iron porphyrin which acts as an electrophile and interacts with Keap1's cysteine residue.", "conclusion": "To prevent cells from oxidative stress, molecular hydrogen activates the Nrf2 pathway. To activate the Nrf2 pathway, molecular hydrogen oxidizes the iron porphyrin which acts as an electrophile and interacts with Keap1's cysteine residue." }, { "pmid": "40068089", "year": 2025, "title": "Molecular hydrogen: Mechanism against oxidative stress and application in periodontitis: A review.", "title_en": null, "title_de": "Molekularer Wasserstoff: Mechanismus gegen oxidativen Stress und Anwendung bei Parodontitis: Eine Übersichtsarbeit", "journal": "Medicine", "authors": "Ying et al.", "author_search": "ying ying", "doi": "10.1097/md.0000000000041800", "doi_url": "https://doi.org/10.1097/md.0000000000041800", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40068089/", "url": "https://h2medicine.org/studies/study-ying-2025-mechanism-against-oxidative-stress/", "methods": [ "unspecified" ], "indications": [ "oral-health", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2025 · Ying — Molecular hydrogen: Mechanism against oxidative stress and application in periodontitis: A review", "summary": "Periodontitis is driven by an oxidative stress cascade that current dental treatments only partially address — this review summarises how molecular hydrogen's antioxidant properties could be applied before, during, and after periodontal surgery, and introduces a new benefit-evaluation model (ENFP) for assessing novel agents in dentistry. (Medicine, 2025.)", "assessment": "This is a narrative review with a conceptual contribution (the ENFP model). It makes a logically coherent case for H₂ in periodontitis based on mechanism and general antioxidant evidence, but randomised clinical trial data specifically in periodontitis are not cited. The ENFP framework is an interesting methodological addition for the dental field. The review does not overstate certainty, and its structured three-phase proposal is practically oriented without making unsubstantiated efficacy claims. A useful orientation paper for dental researchers considering H₂ as an adjunct.", "abstract": "Molecular hydrogen, as an effective anti-oxidative stress reagent, has been extensively studied in medicine with new developments continuing to be reported during the years. This review firstly discusses the mechanism of molecular hydrogen of alleviating oxidative stress. Considering the current antioxidant demand in clinical dental treatment, we summarize the progress and future potential of hydrogen's application in periodontitis. Finally, taking its treatment of periodontitis as an example, we develop an Essence-Necessity-Feasibility-Practice (ENFP) benefit evaluation model for whether to introduce new reagents in medical treatment and propose our conclusions on the application of molecular hydrogen before, during, and after periodontal surgeries.", "conclusion": "Considering the current antioxidant demand in clinical dental treatment, we summarize the progress and future potential of hydrogen's application in periodontitis. Finally, taking its treatment of periodontitis as an example, we develop an Essence-Necessity-Feasibility-Practice (ENFP) benefit evaluation model for whether to introduce new reagents in medical treatment and propose our conclusions on" }, { "pmid": "40044939", "year": 2025, "title": "Aging, vascular dysfunction, and the blood-brain barrier: unveiling the pathophysiology of stroke in older adults.", "title_en": null, "title_de": "Alterung, vaskuläre Dysfunktion und die Blut-Hirn-Schranke: Aufdeckung der Pathophysiologie des Schlaganfalls bei älteren Erwachsenen", "journal": "Biogerontology", "authors": "Alaqel et al.", "author_search": "alaqel alaqel", "doi": "10.1007/s10522-025-10209-y", "doi_url": "https://doi.org/10.1007/s10522-025-10209-y", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40044939/", "url": "https://h2medicine.org/studies/study-alaqel-2025-aging-vascular-dysfunction-blood/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise", "neurology", "cardiovascular", "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2025 · Alaqel — Aging, vascular dysfunction, and the blood-brain barrier: unveiling the pathophysiology of stroke in older adults", "summary": "Stroke risk rises sharply with age because aging progressively damages the blood-brain barrier (BBB) through endothelial senescence, oxidative stress, and tight junction protein loss — this review maps these mechanisms and surveys emerging therapeutic approaches, including hydrogen-rich water therapy, aimed at restoring BBB integrity. (Biogerontology, 2025.)", "assessment": "This is a narrative review covering aging-related BBB dysfunction and stroke pathophysiology. Hydrogen-rich water therapy is mentioned briefly as one of five or more candidate approaches — it is not the focus of the paper, and no clinical trial data on H₂ specifically for BBB protection or stroke recovery are presented. The mechanistic coverage of BBB biology and stroke is thorough and well-cited. The therapeutic landscape section, which includes H₂, is largely preclinical and forward-looking. Findings cannot be directly extrapolated to clinical recommendations.", "abstract": "The progressive decline of vascular integrity and blood-brain barrier (BBB) function is associated with aging, a major risk factor for stroke. This review describes the cellular and molecular changes in the brain microvasculature of the neurovascular unit (NVU) that contribute to the development of BBB dysfunction in aging, such as endothelial cell senescence, oxidative stress, and degradation of tight junction proteins. Stroke severity and recovery are exacerbated by BBB breakdown, leading to neuroinflammation, neurotoxicity, and cerebral oedema while identifying molecular mechanisms such as the NLRP3 inflammasome, matrix metalloproteinases (MMPs), and non-coding RNAs (e.g., miRNAs and circRNAs) that drive BBB disruption in aging and stroke. Real-time assessment of BBB permeability in stroke pathophysiology is made possible using advanced imaging techniques, such as dynamic contrast-enhanced MRI and positron emission tomography. Furthermore, biomarkers, including claudin-5, PDGFRβ, or albumin concentration, serve as markers of BBB integrity and vascular health. Restoration of BBB function and stroke recovery with emerging therapeutic strategies, including sirtuin modulators (SIRT1 and SIRT3 activators to enhance endothelial function and mitochondrial health), stem cell-derived extracellular vesicles (iPSC-sEVs for BBB repair and neuroprotection), NLRP3 inflammasome inhibitors (MCC950 to attenuate endothelial pyroptosis and inflammation), hydrogen-rich water therapy (to counteract oxidative stress-induced BBB damage), and neuropeptides such as cortistatin (to regulate neuroinflammation and BBB stability), is promising. This review explores the pathophysiological mechanisms of BBB dysfunction in aging and stroke, their relation to potential therapeutic targets, and novel approaches to improve vascular health and neuroprotection.", "conclusion": "Restoration of BBB function and stroke recovery with emerging therapeutic strategies, including sirtuin modulators (SIRT1 and SIRT3 activators to enhance endothelial function and mitochondrial health), stem cell-derived extracellular vesicles (iPSC-sEVs for BBB repair and neuroprotection), NLRP3 inflammasome inhibitors (MCC950 to attenuate endothelial pyroptosis and inflammation), hydrogen-rich wa" }, { "pmid": "40026178", "year": 2025, "title": "The Roles of Neuroinflammation in l-DOPA-Induced Dyskinesia: Dissecting the Roles of NF-κB and TNF-α for Novel Pharmacological Therapeutic Approaches.", "title_en": null, "title_de": "Die Rolle der Neuroinflammation bei L-DOPA-induzierter Dyskinesie: Aufschlüsselung der Rollen von NF-κB und TNF-α für neuartige pharmakologische therapeutische Ansätze", "journal": "The European journal of neuroscience", "authors": "Zamanian et al.", "author_search": "zamanian zamanian", "doi": "10.1111/ejn.70034", "doi_url": "https://doi.org/10.1111/ejn.70034", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40026178/", "url": "https://h2medicine.org/studies/study-zamanian-2025-roles-neuroinflammation-dopa-induced/", "methods": [ "inhalation" ], "indications": [ "neurology", "skin-aging", "immune-system" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2025 · Zamanian — The Roles of Neuroinflammation in l-DOPA-Induced Dyskinesia: Dissecting the Roles of NF-κB and TNF-α for Novel Pharmacological Therapeutic Approaches", "summary": "Levodopa-induced dyskinesia (LID) — involuntary movements that develop in Parkinson's patients on long-term levodopa therapy — involves neuroinflammation driven by NF-κB and TNF-α; this review surveys pharmacological approaches targeting these pathways, including hydrogen gas inhalation as one agent that reduces pro-inflammatory cytokines associated with dyskinesia. (The European Journal of Neuroscience, 2025.)", "assessment": "This is a narrative review on neuroinflammatory mechanisms in LID. Hydrogen gas inhalation is mentioned as one of several anti-inflammatory candidates — the claim of reduced cytokines in LID is based on animal models, not human clinical trials. No dedicated phase II/III data on H₂ in Parkinson's dyskinesia are cited. The NF-κB/TNF-α mechanistic framework is well-supported by the cited literature and represents a legitimate therapeutic hypothesis. Overall, this is an early-stage, preclinical evidence paper for H₂ in this specific indication; results cannot be directly extrapolated to patients.", "abstract": "Levodopa-induced dyskinesia (LID) is a common and debilitating complication of long-term Parkinson's disease treatment. This review explores the roles of NF-κB and TNF-α signalling pathways in LID pathophysiology and potential therapeutic approaches targeting these mechanisms. Chronic levodopa treatment leads to aberrant neuroplasticity and neuroinflammation, involving activation of NF-κB and increased production of pro-inflammatory cytokines like TNF-α. NF-κB activation in glial cells contributes to sustained neuroinflammation and exacerbates dopaminergic neuron loss. TNF-α levels are elevated in brain regions affected by LID and correlate with dyskinesia severity. Several compounds are involved in mitigating LID by modulating these pathways. Agmatine reduces NF-κB activation and NMDA receptor expression while protecting dopaminergic neurons. Resveratrol and doxycycline demonstrate antidyskinetic effects by attenuating neuroinflammation and TNF-α production. The Rho-kinase (ROCK) inhibitor fasudil and cannabinoid receptor 2 (CB2) receptor agonists also show efficacy in reducing LID severity and neuroinflammation. Hydrogen gas inhalation decreases pro-inflammatory cytokine levels associated with LID. These findings highlight the complex interplay between NF-κB, TNF-α and other neurotransmitter systems in LID pathogenesis. Targeting neuroinflammation and glial activation through these pathways represents a promising strategy for developing novel LID treatments. Further research is needed to fully elucidate the mechanisms and optimize therapeutic approaches targeting NF-κB and TNF-α signalling in LID.", "conclusion": "Targeting neuroinflammation and glial activation through these pathways represents a promising strategy for developing novel LID treatments. Further research is needed to fully elucidate the mechanisms and optimize therapeutic approaches targeting NF-κB and TNF-α signalling in LID." }, { "pmid": "40017254", "year": 2025, "title": "Exploring the Potential of H2 Therapy in Reducing Surgical Complications: A Review on Anti-inflammatory, Antioxidant, and Anti-fibrotic Mechanisms.", "title_en": null, "title_de": "Erkundung des Potenzials der H₂-Therapie zur Reduzierung chirurgischer Komplikationen: Eine Übersichtsarbeit über entzündungshemmende, antioxidative und antifibrotische Mechanismen", "journal": "Current pharmaceutical design", "authors": "Neykhonji et al.", "author_search": "neykhonji neykhonji", "doi": "10.2174/0113816128354067250211052237", "doi_url": "https://doi.org/10.2174/0113816128354067250211052237", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40017254/", "url": "https://h2medicine.org/studies/study-neykhonji-2025-exploring-reducing-surgical-complications/", "methods": [ "unspecified" ], "indications": [ "respiratory", "immune-system", "oxidative-stress", "fundamentals-safety" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2025 · Neykhonji — Exploring the Potential of H₂ Therapy in Reducing Surgical Complications: A Review on Anti-inflammatory, Antioxidant, and Anti-fibrotic Mechanisms", "summary": "Molecular hydrogen shows anti-inflammatory, antioxidant, and anti-fibrotic properties that could make it a candidate for preventing post-surgical adhesions — one of the most common and debilitating complications after abdominal and pelvic surgery. This review, based on a systematic search of PubMed and Google Scholar, traces the molecular pathways by which H₂ may dampen the inflammatory cascade that drives adhesion formation. (Current Pharmaceutical Design, 2025.)", "assessment": "This is a hypothesis-generating review, not a clinical proof of concept. The authors make a scientifically coherent argument, but post-surgical adhesion prevention by H₂ has not been tested in humans. All supporting evidence is indirect — drawn from animal and cell studies on inflammation and fibrosis in contexts other than adhesion. The review is useful as a map of mechanistic rationale and as a call to action for researchers, but it should not be read as evidence that H₂ prevents adhesions in patients. A conflict-of-interest or funding statement was not apparent from the available data.", "abstract": "OBJECTIVE: This review demonstrates the potential role of hydrogen in post-surgical adhesion prevention and calls for further investigation of its molecular pathways, as well as clinical studies to assess its efficacy and safety in a therapeutic setting. METHODS: PubMed and Google Scholar were extensively queried to investigate the potential role of hydrogen in preventing post-surgical adhesions and its underlying mechanisms. RESULTS: Molecular hydrogen exhibits selective antioxidant, anti-inflammatory, and anti-fibrotic properties, holding potential for the treatment and prevention of various disorders, including acute pancreatitis, respiratory diseases, and ischemia-reperfusion damage conditions, among others. Postoperative adhesion is associated with chronic pain, organ dysfunction, and acute complications, fundamentally rooted in inflammation, oxidative stress, and fibrosis. The surgical injury initiates an inflammatory response characterized by immune cell mobilization and an increase in pro-inflammatory cytokine levels, thereby promoting adhesion formation. CONCLUSION: Hydrogen is demonstrated to attenuate the early inflammatory response by down-regulating proinflammatory cytokines alongside its anti-oxidative and anti-fibrotic effects. As a potential therapeutic agent for post-surgical adhesions, hydrogen warrants additional investigation to elucidate the exact molecular pathways responsible for its observed efficacy and safety.", "conclusion": "Hydrogen is demonstrated to attenuate the early inflammatory response by down-regulating proinflammatory cytokines alongside its anti-oxidative and anti-fibrotic effects. As a potential therapeutic agent for post-surgical adhesions, hydrogen warrants additional investigation to elucidate the exact molecular pathways responsible for its observed efficacy and safety." }, { "pmid": "39810534", "year": 2025, "title": "Oral Administration of Hydrogen-rich Water: Biomedical Activities, Potential Mechanisms, and Clinical Applications.", "title_en": null, "title_de": "Orale Verabreichung von wasserstoffreichem Wasser: Biomedizinische Aktivitäten, mögliche Mechanismen und klinische Anwendungen", "journal": "Current pharmaceutical design", "authors": "Meng et al.", "author_search": "meng meng", "doi": "10.2174/0113816128330516241121150719", "doi_url": "https://doi.org/10.2174/0113816128330516241121150719", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39810534/", "url": "https://h2medicine.org/studies/study-meng-2025-oral-administration-biomedical-activities/", "methods": [ "drinking-hrw" ], "indications": [ "metabolic", "cardiovascular", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2025 · Meng — Oral Administration of Hydrogen-rich Water: Biomedical Activities, Potential Mechanisms, and Clinical Applications", "summary": "Hydrogen-rich water (HRW) reduces oxidative stress, modulates inflammation, regulates metabolism, and protects mitochondrial function — this comprehensive review surveys both laboratory evidence and clinical applications of orally consumed HRW. The authors map five proposed mechanisms of action and report its use in adjuvant treatment, disease prevention, and quality-of-life improvement across a range of conditions. (Current Pharmaceutical Design, 2025.)", "assessment": "This is a broad narrative review covering both preclinical mechanisms and clinical uses of HRW. It is a useful entry point into the literature but does not provide quantitative meta-analytical evidence. The mechanistic landscape it describes is genuine and growing, but several hypotheses are still being debated. Clinical findings are summarised without pooled effect sizes, so readers should treat clinical claims as directional rather than definitive. The honest conclusion by the authors — that large trials are still needed — is the appropriate take-away.", "abstract": "Molecular hydrogen (H2) is considered a biological antioxidant. Hydrogen-rich Water (HRW) is regular water that contains dissolved H2 and has become more widely used in recent years. This review summarizes the basic research and clinical applications of HRW consumption to support its use for daily health and clinical treatment. The biological effects of HRW include reducing oxidative stress, exerting antiinflammatory effects, regulating glucose and lipid metabolism, protecting mitochondrial function, and regulating apoptosis. Hypotheses about the mechanisms of H2 include the direct scavenging of toxic free radicals, the Fe-porphyrin biosensor hypothesis, the effect of H2 on biological enzymes, the lipoprotein regulation of H2, and H2 acting on the intestinal barrier. Clinically, HRW has been used for adjuvant treatment, disease prevention, and quality of life improvement. In the future, more in-depth studies and large-scale clinical trials are needed.", "conclusion": "Clinically, HRW has been used for adjuvant treatment, disease prevention, and quality of life improvement. In the future, more in-depth studies and large-scale clinical trials are needed." }, { "pmid": "39807026", "year": 2025, "title": "Application trends of hydrogen-generating nanomaterials for the treatment of ROS-related diseases.", "title_en": null, "title_de": "Anwendungstrends wasserstofferzeugender Nanomaterialien zur Behandlung ROS-assoziierter Erkrankungen", "journal": "Biomaterials science", "authors": "Li et al.", "author_search": "li li", "doi": "10.1039/d4bm01450b", "doi_url": "https://doi.org/10.1039/d4bm01450b", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39807026/", "url": "https://h2medicine.org/studies/study-li-2025-application-trends-generating-nanomaterials/", "methods": [ "inhalation" ], "indications": [ "liver", "neurology", "cardiovascular", "cancer", "kidney-dialysis", "skin-aging", "immune-system", "oxidative-stress", "fundamentals-safety" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2025 · Li — Application Trends of Hydrogen-generating Nanomaterials for the Treatment of ROS-related Diseases", "summary": "Hydrogen-producing nanomaterials allow targeted, sustained delivery of H₂ directly to sites of disease — this review surveys how combining H₂ gas therapy with nanomedicine advances treatment of cancers, neurodegeneration, cardiovascular, liver, kidney, and skin diseases driven by excess reactive oxygen species (ROS). The nanoparticle-based approach overcomes key limitations of conventional inhalation or drinking-water routes. (Biomaterials Science, 2025.)", "assessment": "This is a preclinical review — all discussed disease models are animal or cellular; no human data are presented or claimed. The engineering concepts are innovative, but the path from a nanoparticle-delivered H₂ system in a mouse model to a clinical therapy is long and uncertain. The review is valuable as a research-landscape overview for scientists, not as a basis for therapeutic claims. Readers should note the inherent publication bias toward positive animal results.", "abstract": "Reactive oxygen species (ROS) play essential roles in both physiological and pathological processes. Under physiological conditions, appropriate amounts of ROS play an important role in signaling and regulation in cells. However, too much ROS can lead to many health problems, including inflammation, cancer, delayed wound healing, neurodegenerative diseases (such as Parkinson's disease and Alzheimer's disease), and autoimmune diseases, and oxidative stress from excess ROS is also one of the most critical factors in the pathogenesis of cardiovascular and metabolic diseases such as atherosclerosis. Hydrogen gas effectively removes ROS from the body due to its good antioxidant properties, and hydrogen therapy has become a promising gas therapy strategy due to its inherent safety and stability. The combination of nanomaterials can achieve targeted delivery and effective accumulation of hydrogen, and has some ameliorating effects on diseases. Herein, we summarize the use of hydrogen-producing nanomaterials for the treatment of ROS-related diseases and talk about the prospects for the treatment of other ROS-induced disease models, such as acute kidney injury.", "conclusion": "The combination of nanomaterials can achieve targeted delivery and effective accumulation of hydrogen, and has some ameliorating effects on diseases. Herein, we summarize the use of hydrogen-producing nanomaterials for the treatment of ROS-related diseases and talk about the prospects for the treatment of other ROS-induced disease models, such as acute kidney injury." }, { "pmid": "39042916", "year": 2025, "title": "Hydrogen as an innovative nootropic in health and disease.", "title_en": null, "title_de": "Wasserstoff als innovatives Nootropikum bei Gesundheit und Krankheit", "journal": "Nutrition and health", "authors": "Todorović et al.", "author_search": "todorović todorović", "doi": "10.1177/02601060241266389", "doi_url": "https://doi.org/10.1177/02601060241266389", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39042916/", "url": "https://h2medicine.org/studies/study-todorovic-2025-innovative-nootropic-health-disease/", "methods": [ "unspecified" ], "indications": [ "neurology", "cancer", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2025 · Todorović — Hydrogen as an Innovative Nootropic in Health and Disease", "summary": "Molecular hydrogen may improve executive function, alertness, and memory — this review surveys current evidence for H₂ as a nootropic (cognitive enhancer) in healthy individuals and in patients with neurodegenerative disorders, circadian disruption, and cancer. While findings from a handful of clinical trials are encouraging, the authors stress that evidence remains limited and further investigation is essential. (Nutrition and Health, 2025.)", "assessment": "This review covers an interesting and underexplored application of H₂, but its evidence base is thin. Only a small number of human trials are available, and the review acknowledges this directly. The mechanistic rationale is plausible, but cognitive endpoints are notoriously difficult to measure and prone to placebo effects. No strong clinical recommendation can be derived from this review. It is valuable as a signal and as a map of where future rigorous trials should focus.", "abstract": "Molecular hydrogen (H2, dihydrogen) is an antioxidant and signaling molecule with potent antioxidative, antiapoptotic, and anti-inflammatory properties. Despite the growing interest in H2 as a potential therapeutic agent, the evidence regarding its potential as a nootropic remains limited. Only a handful of studies on the human population have evaluated its effects, although there are suggestive indications of its efficacy. The present paper overviews H2's potential as a novel agent for improving cognitive functions in health and disease contexts, highlighting its mechanisms of action and areas for further investigation. Current evidence suggests that H2 improves executive function, alertness and memory in several clinical trials, from healthy young and elderly individuals to individuals with altered circadian rhythms, neurodegenerative disorders, and cancer. Further investigations are needed to confirm the potential positive effects of dihydrogen as a nootropic agent in both health and disease.", "conclusion": "Current evidence suggests that H2 improves executive function, alertness and memory in several clinical trials, from healthy young and elderly individuals to individuals with altered circadian rhythms, neurodegenerative disorders, and cancer. Further investigations are needed to confirm the potential positive effects of dihydrogen as a nootropic agent in both health and disease." }, { "pmid": "39923133", "year": 2025, "title": "Molecular hydrogen inhalation modulates resting metabolism in healthy females: findings from a randomized, double-blind, placebo-controlled crossover study", "title_en": null, "title_de": "Die Inhalation von molekularem Wasserstoff moduliert den Ruhe-Stoffwechsel bei gesunden Frauen: Ergebnisse einer randomisierten, doppelblinden, placebokontrollierten Crossover-Studie", "journal": "Medical Gas Research", "authors": "Grepl et al.", "author_search": "grepl grepl", "doi": "10.4103/mgr.medgasres-d-24-00085", "doi_url": "https://doi.org/10.4103/mgr.medgasres-d-24-00085", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39923133/", "url": "https://h2medicine.org/studies/study-grepl-2025-inhalation-resting-metabolism-healthy-females/", "methods": [ "inhalation", "bath-topical" ], "indications": [ "metabolic", "oxidative-stress" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2025 · Grepl — Molecular hydrogen inhalation modulates resting metabolism in healthy females: findings from a randomized, double-blind, placebo-controlled crossover study", "summary": "Breathing hydrogen for 60 minutes shifts resting metabolism toward fat burning. In a randomized double-blind crossover trial (20 healthy women), H₂ inhalation significantly lowered the respiratory quotient — a marker of more fat oxidation — especially in participants with higher body fat percentage. (Medical Gas Research, 2025.)", "assessment": "Relevant for H₂ inhalation products and the topic of metabolism/weight management, because a metabolic effect of H₂ is shown here, not just an antioxidant one. The crossover double-blind design is methodologically strong: each participant is her own control, which increases the validity despite the small sample. Limitation, stated honestly: n = 20, exclusively young, physically active women — no transferability to men or older/overweight people without further studies. This is an acute 60-minute effect; an actual reduction in weight or body fat over time was not investigated. A sister study on oxygen saturation comes from the same research group (Palacký University Olomouc).", "abstract": "Initially, molecular hydrogen was considered a physiologically inert and non-functional gas. However, experimental and clinical studies have shown that molecular hydrogen has anti-inflammatory, anti-apoptotic, and strong selective antioxidant effects. This study aimed to evaluate the effects of 60 minutes of molecular hydrogen inhalation on respiratory gas analysis parameters using a randomized, double-blind, placebo-controlled, crossover design. The study was conducted at Faculty of Physical Culture, Palacký University Olomouc from September 2022 to March 2023. Twenty, physically active female participants aged 22.1 ± 1.6 years who inhaled either molecular hydrogen or ambient air through a nasal cannula (300 mL/min) for 60 minutes while resting were included in this study. Metabolic response was measured using indirect calorimetry. Breath-by-breath data were averaged over four 15-minute intervals. Compared with placebo (ambient air), molecular hydrogen inhalation significantly decreased respiratory exchange ratio and ventilation across all intervals. Furthermore, the change in respiratory exchange ratio was negatively correlated with body fat percentage from 30 minutes onwards. In conclusion, 60 minutes of resting molecular hydrogen inhalation significantly increased resting fat oxidation, as evidenced by decreased respiratory exchange ratio, particularly in individuals with higher body fat percentages.", "conclusion": "Furthermore, the change in respiratory exchange ratio was negatively correlated with body fat percentage from 30 minutes onwards. In conclusion, 60 minutes of resting molecular hydrogen inhalation significantly increased resting fat oxidation, as evidenced by decreased respiratory exchange ratio, particularly in individuals with higher body fat percentages." }, { "pmid": "40376695", "year": 2025, "title": "Hydrogen-Rich Water Decreases Muscle Damage and Improves Power Endurance in Elite Athletes: A Randomized, Double-Blinded, Placebo-Controlled Trial", "title_en": null, "title_de": "Wasserstoffreiches Wasser verringert Muskelschäden und verbessert die Kraftausdauer bei Spitzensportlern: eine randomisierte, doppelblinde, placebokontrollierte Studie", "journal": "Journal of Lifestyle Medicine", "authors": "Ogannisyan et al.", "author_search": "ogannisyan ogannisyan", "doi": "10.15280/jlm.2025.15.1.8", "doi_url": "https://doi.org/10.15280/jlm.2025.15.1.8", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40376695/", "url": "https://h2medicine.org/studies/study-ogannisyan-2025-hydrogen-rich-water-muscle-damage-power-endurance-elite-athletes/", "methods": [ "tablets", "drinking-hrw" ], "indications": [ "sports-exercise", "oxidative-stress" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2025 · Ogannisyan — Hydrogen-Rich Water Decreases Muscle Damage and Improves Power Endurance in Elite Athletes: A Randomized, Double-Blinded, Placebo-Controlled Trial", "summary": "Hydrogen-rich water reduces muscle damage and boosts power performance in competitive female athletes. In a randomized double-blind placebo design (22 elite female athletes), total creatine kinase fell significantly, torque after intensive exertion rose, and body fat percentage went down (all p (Journal of Lifestyle Medicine, 2025 — one of the few H₂ studies in real elite athletes.)", "assessment": "Directly relevant to H₂ supplementation in competitive sport, because the study design (double-blind, placebo-controlled) largely excludes placebo and expectation effects — precisely in sport, where motivation plays a big role. The finding fits mechanistically with the antioxidant profile of H₂: less oxidative stress after exertion, less muscle damage. Limitation, stated honestly: very small sample (n = 22), only women, only two sports — transferability is limited. Stress and recovery values (RESTQ-Sport) showed no effect, and the mechanism of action remains unexplained according to the authors.", "abstract": "Physical activity significantly increases the production of reactive oxygen species in the body. Molecular hydrogen has been shown to have safe and effective antioxidant properties on athletes. However, research on elite athletes is scarce. A randomized, double-blinded, placebo-controlled trial was conducted with 22 female elite athletes participating in handball and skeleton sports. The first group received hydrogen-rich water (HRW)-generating tablets, whereas the second group consumed a visually and organoleptically similar placebo. Various assessments were performed during HRW intake, such as anthropometric and biochemical measurements, stress, and recovery parameters, as well as biomechanical testing. HRW consumption resulted inan increase in muscle mass and a reduction in fat mass (p < 0.05). However, HRW did not significantly affect stress or recovery rates, as determined by the Recovery-Stress Questionnaire-Sport questionnaire. However, the HRW group exhibited a significant increase in torque, particularly after an intensive exercise test (p < 0.05). Moreover, HRW intake led to a reduction in total creatine kinase, vitamin C, and beta-carotene contents (p < 0.05), whereas the vitamin E and interleukin-10 levels increased compared with baseline levels (p < 0.05). The HRW-generating tablets were found to be safe and well-tolerated by the participants. These tablets also exerted ergogenic effects by reducing body fat percentage, increasing muscle mass percentage, improving maximal torque, decreasing muscle damage, and positively modulating the exercise-induced inflammatory and antioxidant responses to exercise. Although the mechanism of action of HRW remains unclear, these effects observed indicate its potential for diverse applications in high-performance sports.", "conclusion": "These tablets also exerted ergogenic effects by reducing body fat percentage, increasing muscle mass percentage, improving maximal torque, decreasing muscle damage, and positively modulating the exercise-induced inflammatory and antioxidant responses to exercise. Although the mechanism of action of HRW remains unclear, these effects observed indicate its potential for diverse applications in high-" }, { "pmid": "40525414", "year": 2025, "title": "The effects of drinking hydrogen-rich water for six weeks on exercise-related biomarkers in exercise-naïve men and women over 50 years following resistance training program: a randomized controlled pilot trial", "title_en": null, "title_de": "Die Effekte des sechswöchigen Trinkens von wasserstoffreichem Wasser auf belastungsbezogene Biomarker bei sportungewohnten Männern und Frauen über 50 Jahren nach einem Krafttrainingsprogramm: eine randomisierte, kontrollierte Pilotstudie", "journal": "Research in Sports Medicine", "authors": "Kuzmanovic et al.", "author_search": "kuzmanovic kuzmanovic", "doi": "10.1080/15438627.2025.2521474", "doi_url": "https://doi.org/10.1080/15438627.2025.2521474", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40525414/", "url": "https://h2medicine.org/studies/study-kuzmanovic-2025-drinking-hrw-exercise-biomarkers-over-50-resistance/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise", "metabolic", "oxidative-stress" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2025 · Kuzmanovic — The effects of drinking hydrogen-rich water for six weeks on exercise-related biomarkers in exercise-naïve men and women over 50 years following resistance training program: a randomized controlled pilot trial", "summary": "Hydrogen-rich water supports strength training from 50 on: In a randomized, double-blind pilot RCT (n = 27, age ~58 yrs), 6 weeks of H₂ water lowered markers of acute muscle damage significantly more than placebo, improved the blood lipid profile (total and LDL cholesterol ↓) and raised free testosterone (all p ≤ 0.05). (Research in Sports Medicine, 2025.)", "assessment": "Directly relevant to H₂ supplementation in active aging and beginner strength training — exactly the demographic group of particular interest here. The double-blind, placebo-controlled design is strong and rules out expectation effects. Honest about the content: the effect shows up in the biomarkers (muscle damage, blood lipids), not in pure strength performance, which increased equally well in both groups. Limitation, stated honestly: explicitly declared a pilot study, small sample (n = 27), short duration (6 weeks), co-author (Ostojic) is a prolific H₂ researcher (possible confirmation bias). No superiority evidence for training performance itself.", "abstract": "The primary objective of this pilot study was to assess the impact of consuming hydrogen-rich water (HRW) for a duration of six weeks on exercise-related biomarkers in previously untrained men and women aged over 50 years, subsequent to a resistance training program. Twenty-seven apparently healthy middle-aged adults (age 57.6 ± 6.7 years; 18 females) voluntarily provided written consent to participate in this randomized, placebo-controlled experimental trial. All participants were allocated in a double-blind parallel-group design to receive either HRW (12 mg of dihydrogen per serving) or control water (<0.1 ppm of dihydrogen) administered two times per day during a 6-week intervention interval. Muscle performance indices showed a significant improvement following both HRW and control water interventions compared to the baseline values (p ≤ 0.05). HRW led to a significant increase in serum free testosterone and cortisol levels, along with reductions in total cholesterol and LDL-cholesterol levels at the follow-up (p ≤ 0.05). Moreover, HRW significantly outperformed the control water in reducing biomarkers of acute muscular damage caused by resistance exercise (p ≤ 0.05) and tended to outcompete placebo in improving sleep quality (p = 0.119). HRW could be advanced as a risk-free and effective beverage for promoting training-specific adaptations in exercise-naïve men and women over 50 years of age.", "conclusion": "Moreover, HRW significantly outperformed the control water in reducing biomarkers of acute muscular damage caused by resistance exercise (p ≤ 0.05) and tended to outcompete placebo in improving sleep quality (p = 0.119). HRW could be advanced as a risk-free and effective beverage for promoting training-specific adaptations in exercise-naïve men and women over 50 years of age." }, { "pmid": "40731803", "year": 2025, "title": "Pre-Exercise Ingestion of Hydrogen-Rich Cold Water Enhances Endurance Performance and Lactate Response in Heat", "title_en": null, "title_de": "Die Einnahme von wasserstoffreichem Kaltwasser vor dem Sport verbessert die Ausdauerleistung und die Laktatreaktion bei Hitze", "journal": "Medicina (Kaunas)", "authors": "Khlifi et al.", "author_search": "khlifi khlifi", "doi": "10.3390/medicina61071173", "doi_url": "https://doi.org/10.3390/medicina61071173", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40731803/", "url": "https://h2medicine.org/studies/study-khlifi-2025-pre-exercise-cold-water-endurance-heat/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise", "oxidative-stress" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2025 · Khlifi — Pre-Exercise Ingestion of Hydrogen-Rich Cold Water Enhances Endurance Performance and Lactate Response in Heat", "summary": "Hydrogen-rich cold water before exercise improves endurance performance in heat and dampens the lactate rise. In a double-blind crossover it significantly raised maximal aerobic speed and the number of shuttle-run repetitions versus control (each p (Medicina, 2025.)", "assessment": "Directly relevant to endurance performance under heat stress, especially for heat scenarios. The findings (more endurance, less lactate, better perception) fit the antioxidant and anti-fatigue profile of H₂. Limitation, stated honestly: the H₂ effect is mixed with the cold-water pre-cooling effect — without a separate pure H₂ arm, the isolated H₂ contribution remains open. Crossover design (evidence level 3); sample size not quantified in the abstract. Solid signal, but causally not fully attributable to H₂.", "abstract": "Background and Objectives: Hyperthermia significantly limits endurance performance in hot environments. To enhance heat loss and optimize athletic performance, pre-cooling interventions can be employed to accelerate body cooling. Therefore, the aim of this study was to evaluate the effects of an internal pre-cooling intervention combined with external pre-cooling or hydrogen-rich water on endurance performance in the heat. Materials and Methods: In a double-blind crossover with counterbalanced trials, all participants underwent a shuttle run test after 30 min under the following conditions: (1) hydrogen-rich cold water ingestion (HRCW); (2) cold water ingestion and external pre-cooling (IEPC); and (3) cold-water ingestion (control). Maximal aerobic speed (MAS), number of shuttle run repetitions, dehydration, temperature, heart rate (HR), rate of perceived exertion (RPE), blood lactate, and feeling scale (FS) were measured during the 20 m shuttle run test. Results: Our results revealed a significant variation in dehydration, MAS, number of shuttle run repetitions, blood lactate, RPE, and FS (p = [0.001-0.036]); additionally, a significant group × time interaction was found for body temperature (p = 0.021). Post hoc tests revealed a significant change for MAS (HRCW: p < 0.001), number of shuttle run repetitions (HRCW: p < 0.001), dehydration (HRCW: p= 0.009; IEPC: p = 0.008), blood lactate (HRCW: p < 0.001; IEPC: p < 0.001), RPE (HRCW: p = 0.05; IEPC: p = 0.004), and FS (HRCW: p = 0.05; IEPC: p = 0.004), as well as a significant decrease in body temperature (IEPC: p < 0.001; HRCW: p = 0.028) compared to the control condition after the test. However, no significant differences were reported in HR among the different conditions. Conclusions: In conclusion, findings from this study suggest that ingesting hydrogen-rich cold water effectively mitigates the effects of heat stress, thereby improving endurance performance, enhancing mood, and reducing ratings of perceived exertion.", "conclusion": "In conclusion, findings from this study suggest that ingesting hydrogen-rich cold water effectively mitigates the effects of heat stress, thereby improving endurance performance, enhancing mood, and reducing ratings of perceived exertion." }, { "pmid": "40731927", "year": 2025, "title": "The Effects of 8-Week Hydrogen-Rich Water Consumption on Appetite, Body Composition, Sleep Quality, and Circulating Glucagon-like Peptide-1 in Obese Men and Women (HYDRAPPET): A Randomized Controlled Trial", "title_en": null, "title_de": "Die Effekte des achtwöchigen Konsums von wasserstoffreichem Wasser auf Appetit, Körperzusammensetzung, Schlafqualität und zirkulierendes Glucagon-like Peptide-1 bei adipösen Männern und Frauen (HYDRAPPET): eine randomisierte kontrollierte Studie", "journal": "Medicina (Kaunas)", "authors": "Todorovic et al.", "author_search": "todorovic todorovic", "doi": "10.3390/medicina61071299", "doi_url": "https://doi.org/10.3390/medicina61071299", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40731927/", "url": "https://h2medicine.org/studies/study-todorovic-2025-8-week-appetite-body-composition-sleep-glp-1-obese/", "methods": [ "drinking-hrw" ], "indications": [ "metabolic", "neurology" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2025 · Todorovic — The Effects of 8-Week Hydrogen-Rich Water Consumption on Appetite, Body Composition, Sleep Quality, and Circulating Glucagon-like Peptide-1 in Obese Men and Women (HYDRAPPET): A Randomized Controlled Trial", "summary": "Hydrogen-rich water curbs food cravings and raises the satiety hormone GLP-1 in obese people. In a randomized, double-blind placebo design (36 participants, 1 L/day with 15 mg H₂, 8 weeks), cravings, total and LDL cholesterol fell, sleep quality improved and plasma GLP-1 rose. (Medicina, 2025 — registered on ClinicalTrials.gov NCT06722326.)", "assessment": "Medically relevant to appetite and metabolic regulation, because the study links one of the currently most-discussed topics in metabolic medicine — GLP-1 and appetite regulation — with a defined H₂ content (15 mg/L) and a clean double-blind design, plus proper registration (NCT06722326). This shifts the mechanistic picture from „antioxidant“ toward „metabolic lever“. Limitation, stated honestly: small sample (n = 36), only 8 weeks, and conspicuously many findings exactly at the p = 0.05 threshold — this is statistically fragile and does not allow strong causal statements. Patient-reported endpoints (cravings, sleep) are prone to residual bias.", "abstract": "Background and Objectives: Preliminary studies indicate that dihydrogen (H2) may affect molecular pathways involved in appetite regulation; however, its role in influencing patient-reported appetite outcomes in individuals with obesity remains uncertain. This randomized, placebo-controlled, double-blind trial aimed to evaluate the effects of H2 supplementation on appetite, body composition, sleep quality, obesity-specific quality of life, and related biomarkers in obese men and women. Materials and Methods: The study included 36 participants (24 females; age 42.1 ± 13.2 years; BMI 30.8 ± 4.2 kg/m2) randomized to receive either 1.0 L of hydrogen-rich water (15 mg of H2) or 1.0 L of control water (0 mg of H2) daily for eight weeks. Results: The results demonstrated that hydrogen-rich water significantly mitigated cravings (p = 0.05), improved subjective sleep quality (p = 0.05), reduced total cholesterol (p = 0.02) and LDL cholesterol (p = 0.04), and increased plasma glucagon-like peptide-1 levels (p = 0.05) compared to the control. No severe adverse effects were reported throughout the trial. Conclusions: These findings suggest that hydrogen-rich water may serve as a safe and effective dietary strategy to address appetite regulation and related metabolic indices in individuals with obesity. The study is registered at ClinicalTrials.gov (NCT06722326).", "conclusion": "These findings suggest that hydrogen-rich water may serve as a safe and effective dietary strategy to address appetite regulation and related metabolic indices in individuals with obesity. The study is registered at ClinicalTrials.gov (NCT06722326)." }, { "pmid": "40922182", "year": 2025, "title": "Hydrogen-rich water supplementation attenuates oxidative stress and inflammation in chronic high-altitude disease patients: A double-blind randomized placebo-controlled study", "title_en": null, "title_de": "Die Supplementierung mit wasserstoffreichem Wasser dämpft oxidativen Stress und Entzündung bei Patienten mit chronischer Höhenkrankheit: eine doppelblinde, randomisierte, placebokontrollierte Studie", "journal": "Food Research International", "authors": "Zhang et al.", "author_search": "zhang zhang", "doi": "10.1016/j.foodres.2025.117118", "doi_url": "https://doi.org/10.1016/j.foodres.2025.117118", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40922182/", "url": "https://h2medicine.org/studies/study-zhang-2025-high-altitude-disease-oxidative-stress-inflammation/", "methods": [ "drinking-hrw" ], "indications": [ "oxidative-stress", "immune-system", "respiratory" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2025 · Zhang — Hydrogen-rich water supplementation attenuates oxidative stress and inflammation in chronic high-altitude disease patients: A double-blind randomized placebo-controlled study", "summary": "In chronic high-altitude disease, 60 days of hydrogen-rich water dampened inflammation-related gene pathways. In the double-blind RCT (43 evaluated patients), inflammation and cytokine pathways were upregulated in the placebo group, while hydrogen-rich water significantly downregulated them — the direct markers showed a (non-significant) downward trend. (Food Research International, 2025.)", "assessment": "Relevant to inflammation and oxidative stress in chronic high-altitude disease, because a mechanistically deep piece of evidence is delivered here: H₂ not only modulates markers but dampens inflammatory gene pathways (TNF, IL-1β etc.) — fitting the anti-inflammatory mechanistic picture of H₂. Limitation, stated honestly: the directly measured oxidative/inflammatory markers reached only a non-significant downward trend — the main statement rests on transcriptome/network analyses. Small sample reduced by drop-outs (n = 43). Solid double-blind RCT design (evidence level 3), but the main finding is at the molecular, not the clinical level.", "abstract": "Chronic high-altitude disease (CHAD) is primarily driven by oxidative damage and inflammation. Hydrogen-rich water (HRW) is a novel functional food with demonstrated antioxidant and anti-inflammatory properties. However, its potential effects on inflammation and oxidative stress in CHAD remain unexplored. In this study, 50 participants with CHAD were recruited and assigned to the HRW or placebo water (PW) group for 60 days. After seven participants were lost to follow-up, 43 participants (HRW, n = 23; PW, n = 20) completed the intervention and were included in the analysis. Oxidative stress indicators and inflammation-related immune cells were evaluated before and after treatment, and transcriptional profiles of all participants were analyzed to determine the potential mechanism of HRW in CHAD. Baseline characteristics did not differ significantly between the two groups. Enrichment analysis showed that differentially expressed genes in the PW group between pre- and post-intervention were predominantly associated with inflammation- and cytokine-related pathways, whereas HRW treatment significantly downregulated these pathways. By integrating weighted gene co-expression network analysis and protein-protein interaction network analysis we identified six hub genes, including tumor necrosis factor, interleukin-1 beta, C-C motif chemokine ligand 3, C-C motif chemokine ligand 3-like 1, C-C motif chemokine ligand 4-like 2, and radiation-inducible immediate-early response 3. Furthermore, measurements of oxidative stress and inflammatory markers indicated a non-significant downward trend in oxidative stress and inflammation in patients with CHAD after HRW intake for 60 days. These results suggest the potential protective role of HRW in CHAD, providing a novel adjuvant therapy for CHAD.", "conclusion": "Furthermore, measurements of oxidative stress and inflammatory markers indicated a non-significant downward trend in oxidative stress and inflammation in patients with CHAD after HRW intake for 60 days. These results suggest the potential protective role of HRW in CHAD, providing a novel adjuvant therapy for CHAD." }, { "pmid": "41384523", "year": 2025, "title": "[Effectiveness of using non-drug technologies to increase stress resistance in persons with extreme work profile and susceptible for professional burnout].", "title_en": null, "title_de": "Wirksamkeit nichtmedikamentöser Technologien zur Steigerung der Stressresistenz bei Personen mit extremem Arbeitsprofil und Anfälligkeit für berufliches Burnout", "journal": "Voprosy kurortologii, fizioterapii, i lechebnoi fizicheskoi kultury", "authors": "Korchazhkina et al.", "author_search": "korchazhkina korchazhkina", "doi": "10.17116/kurort202510205291", "doi_url": "https://doi.org/10.17116/kurort202510205291", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41384523/", "url": "https://h2medicine.org/studies/study-korchazhkina-2025-non-drug-technologies-increase/", "methods": [ "unspecified" ], "indications": [ "sports-exercise" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2025 · Korchazhkina — Effectiveness of Non-Drug Technologies to Increase Stress Resistance in Persons with Extreme Work Profiles and Susceptibility for Professional Burnout", "summary": "Medical workers with professional burnout showed measurable improvements in stress resistance and psychological wellbeing after courses of non-drug physical therapies — including hydrogen therapy — compared to exercise and psychocorrection alone. The combination of all physical factors (cryotherapy, magnetic therapy, hypoxic-hyperoxytherapy, and hydrogen therapy) produced the strongest synergistic effect. Hydrogen therapy as a standalone add-on improved outcomes by approximately 12–23% relative to the control group. (Voprosy kurortologii, fizioterapii, i lechebnoi fizicheskoi kultury, 2025.)", "assessment": "This study documents that hydrogen therapy was part of a physical therapy protocol that showed benefit for burnout-related stress markers in medical workers — but no standalone placebo-controlled hydrogen arm was included. The 12–23% improvement attributed to each mono-add-on (including hydrogen) cannot be cleanly separated from the shared exercise/psychocorrection baseline. The MBI, DASS, and PSM-25 instruments are validated, which is a strength. Key limitations: no blinding described for hydrogen vs. other gas exposures, no sham hydrogen condition, Russian-language journal with limited peer-review transparency. The result is suggestive — not confirmatory — that H₂ may contribute to burnout recovery within a physiotherapy bundle.", "abstract": "UNLABELLED: The high prevalence of professional burnout syndrome among medical workers significantly actualizes the search for the most effective methods aimed at reducing the severity of the negative consequences of professional stress. A certain perspective in solving this problem is associated with the course use of non-drug technologies, the sanogenetic potential of which ensures the implementation of high efficiency in the correction of the main manifestations of professional burnout. The complex use of therapeutic physical factors allows achieving a pronounced clinical result due to their synergistic interaction. OBJECTIVE: Comparative analysis of the efficiency of the course use of non-drug technologies (physical exercises, psychocorrection, general air cryotherapy, general magnetic therapy, hypoxic-hyperoxytherapy, hydrogen therapy and their combinations) in the correction of stress resistance and manifestations of professional burnout in medical workers. MATERIAL AND METHODS: The studies were conducted on the basis of the Federal State Budgetary Scientific Institution Russian Scientific Center of Surgery named after academician B.V. Petrovsky with the participation of 150 patients from among medical personnel aged 30 to 60 years. Using the simple fixed randomization method, all patients were divided into 6 groups: control (n=25), comparison groups 1-4 (n=25 each), and the main group (n=25). Patients in all groups received a course of physical exercises and psychological correction. For the control group, this type of correction was exhaustive. In comparison group 1, a course of general air cryotherapy was additionally carried out; comparison group 2 additionally received a course of general magnetic therapy procedures; comparison group 3 additionally received a course of hypoxic-hyperoxytherapy; comparison group 4 additionally received a course of hydrogen therapy; in the main group, patients received a course of complex exposure to therapeutic physical factors. The study design provided for a double examination of patients in all groups using the MBI questionnaire and the DASS and PSM-25 scales. RESULTS: Conducting a course of correction of the state of professional burnout made it possible to establish that its effectiveness was largely determined by the type of physical factor used. Less pronounced changes were noted in the control group with the use of physical exercises and psychological correction. Additional course application of therapeutic physical factors in the monofactorial impact mode (general air cryotherapy, general magnetic therapy, hypoxic-hyperoxytherapy and hydrogen therapy; respectively comparison groups 1-4) was accompanied by an increase in the positive dynamics of the assessed indicators by 12-23%. The complex use of all physiotherapeutic effects, implemented in the main group, caused the development of the most pronounced corrective effect. CONCLUSION: The use of non-drug technologies allows achieving high efficiency in the correction of stress resistance and manifestations of professional achievement in medical workers. The maximum corrective effect, manifested with the complex use of physical factors, is the result of the synergistic interaction of various physiotherapeutic technologies, implemented in the form of potentiation of sanogenetic mechanisms aimed at normalizing the psycho-emotional status of individuals with an extreme profile of service activity.", "conclusion": "The use of non-drug technologies allows achieving high efficiency in the correction of stress resistance and manifestations of professional achievement in medical workers. The maximum corrective effect, manifested with the complex use of physical factors, is the result of the synergistic interaction of various physiotherapeutic technologies, implemented in the form of potentiation of sanogenetic mechanisms aimed at normalizing the psycho-emotional status of individuals with an extreme profile of" }, { "pmid": "40327618", "year": 2025, "title": "[Efficiency and safety of the integrated use of medical gases thermal heliox, nitric oxide and molecular hydrogen in patients with exacerbation of chronic obstructive pulmonary disease complicated by hypoxemic, hypercapnic respiratory failure and secondary pulmonary arterial hypertension in the post-COVID period].", "title_en": null, "title_de": "Effizienz und Sicherheit des kombinierten Einsatzes medizinischer Gase – thermisches Heliox, Stickstoffmonoxid und molekularer Wasserstoff – bei Patienten mit COPD-Exazerbation, respiratorischer Insuffizienz und pulmonalarterieller Hypertonie in der Post-COVID-Phase", "journal": "Terapevticheskii arkhiv", "authors": "Shogenova", "author_search": "shogenova shogenova", "doi": "10.26442/00403660.2025.03.203131", "doi_url": "https://doi.org/10.26442/00403660.2025.03.203131", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40327618/", "url": "https://h2medicine.org/studies/study-shogenova-2025-efficiency-integrated-use-medical/", "methods": [ "unspecified" ], "indications": [ "liver", "sports-exercise", "cardiovascular", "respiratory", "fundamentals-safety" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2025 · Shogenova — Efficiency and Safety of the Combined Use of Thermal Heliox, Nitric Oxide and Molecular Hydrogen in COPD Exacerbation with Respiratory Failure and Pulmonary Hypertension in the Post-COVID Period", "summary": "In patients hospitalized with severe COPD exacerbation after COVID-19, combining three medical gases — thermal heliox, nitric oxide, and molecular hydrogen (H₂) — alongside standard therapy produced better improvements in breathing, gas exchange, and exercise tolerance than any single gas used alone. The triple combination was safe and reduced markers of vascular dysfunction and metabolic disturbance. This is one of few clinical studies testing H₂ inhalation as part of intensive respiratory care. (Terapevticheskii arkhiv, 2025.)", "assessment": "A meaningful clinical study testing H₂ as one component of multi-gas inhalation therapy in a challenging post-COVID respiratory population. The triple combination benefit over mono-gas comparators is noteworthy, though the study cannot isolate H₂'s individual contribution since no group received only H₂ vs. placebo gas. Key limitations: no blinding described (gases differ in physical properties), no explicit statistical values in abstract, single-center Russian study, small group sizes (n=18–22 per arm). The safety finding — no adverse events — is clinically relevant given that H₂ inhalation in ventilated patients is a safety-relevant question. The study supports feasibility and directional benefit rather than providing high-confidence effect estimates.", "abstract": "AIM: To study the efficacy and safety of the combined use of thermal heliox (t-He/O2), nitric oxide (NO) and molecular hydrogen (H2) in patients with exacerbation of chronic obstructive pulmonary disease (COPD) complicated by hypoxemic, hypercapnic respiratory failure (RF) and secondary pulmonary arterial hypertension (PAH) in the post-COVID period. MATERIALS AND METHODS: The randomized, comparative, controlled, parallel study included patients (n=100, 52 men and 48 women) with exacerbation of COPD levels of evidence C and D (GOLD 2021-2023) with hypoxemic, hypercapnic respiratory failure and secondary PAH, who had pneumonia caused by SARS-CoV-2 before hospitalization. Patients with similar demographic, clinical, and functional parameters, who received non-invasive ventilation (NIV) and oxygen (O2) along with standard drug therapy, were divided into 5 groups: Group 1 (main): (n=22: 12 men, 10 women, who received t-He/O2, NO, and H2 sequentially); Group 2 (n=20: 10 men, 10 women, who received t-He/O2 and NO); Group 3 (n=20: 11 men, 9 women, who received t-He/O2 and H2); Group 4 (n=18: 10 men, 8 women, who received NO and H2); Group 5 (control) (n=20: 9 men, 11 women). The dynamics of the clinical condition of patients, gas exchange in the lungs, acid-base balance, left-to-right discharge fraction, hemodynamic parameters, and exercise tolerance were assessed. RESULTS: A positive effect of the complex use of medical gases on the clinical condition of patients, gas exchange parameters in the lungs, metabolism, hemodynamic parameters and exercise tolerance was found in comparison with these parameters in patients who received medical gases separately and with the control group. CONCLUSION: The combination of t-He/O2, NO and H2 with simultaneous pathogenetic therapy and NIV in patients with exacerbation of COPD complicated by hypoxemic, hypercapnic RF and secondary PAH in the post-COVID period is safe and more effective compared to groups receiving each medical gas separately. Complex therapy improves the clinical condition of patients, reduces signs of hypoxemia and hypercapnia, vascular endothelial dysfunction, metabolic disorders and increases tolerance to physical activity by normalizing gas exchange in the lungs, increasing oxygen delivery to tissues, reducing the shunt fraction, and restoring metabolism.", "conclusion": "The combination of t-He/O2, NO and H2 with simultaneous pathogenetic therapy and NIV in patients with exacerbation of COPD complicated by hypoxemic, hypercapnic RF and secondary PAH in the post-COVID period is safe and more effective compared to groups receiving each medical gas separately. Complex therapy improves the clinical condition of patients, reduces signs of hypoxemia and hypercapnia, vascular endothelial dysfunction, metabolic disorders and increases tolerance to physical activity by n" }, { "pmid": "41384514", "year": 2025, "title": "[Biochemical markers of stress in medical workers with occupational burnout syndrome and their dynamics in the application of physiotherapeutic factors].", "title_en": null, "title_de": "Biochemische Stressmarker bei medizinischem Personal mit berufsbedingtem Burnout-Syndrom und ihre Dynamik unter Anwendung physiotherapeutischer Faktoren", "journal": "Voprosy kurortologii, fizioterapii, i lechebnoi fizicheskoi kultury", "authors": "Kotenko et al.", "author_search": "kotenko kotenko", "doi": "10.17116/kurort202510205217", "doi_url": "https://doi.org/10.17116/kurort202510205217", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41384514/", "url": "https://h2medicine.org/studies/study-kotenko-2025-biochemical-markers-stress-medical/", "methods": [ "unspecified" ], "indications": [ "metabolic", "sports-exercise", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2025 · Kotenko et al. — Biochemical Markers of Stress in Medical Workers With Occupational Burnout Syndrome and Their Dynamics Under Physiotherapeutic Factors", "summary": "In 175 healthcare professionals diagnosed with occupational burnout syndrome, various non-drug physiotherapy interventions — including hydrogen therapy — were tested in a randomised design. Hydrogen therapy alone improved burnout and oxidative stress markers by 12–38 % compared to exercise and psychocorrection alone; the greatest benefit came from combining all physiotherapy approaches together. (Voprosy Kurortologii, Fizioterapii i Lechebnoy Fizicheskoy Kultury, 2025.)", "assessment": "A randomised comparative study — stronger design than case reports, but with important limitations. Hydrogen therapy as a standalone add-on showed a modest, real-world benefit in a relevant population (burnt-out healthcare workers). Key limitations: hydrogen therapy protocol not described (type, dose, frequency unknown); small group sizes (n = 25 each); published in a Russian-language journal (abstract quality may not fully represent the original methodology); no blinding mentioned; short-term outcome only. The finding that combination physiotherapy is superior to any single modality is robust and clinically actionable — but the specific contribution of H₂ within the combination cannot be isolated.", "abstract": "UNLABELLED: Professional burnout syndrome is becoming an increasingly important social and medical problem, as it can occur in almost every third doctor or nurse. This syndrome is based on chronic stress, which provokes the development of a close relationship between the indicators of various psychological tests and questionnaires, hormonal and biochemical markers of metabolic disorders of carbohydrates and lipids, as well as parameters characterizing oxidative stress. One of the promising directions in the treatment and prevention of occupational burnout syndrome is physiotherapy technologies with the combined use of factors with a fundamentally different mechanism of action, which, due to synergistic effects, can significantly increase the effectiveness of therapeutic effects. OBJECTIVE: To evaluate the possibility of using non-drug technologies (physical exercises, psychocorrection, general air cryotherapy, general magnetic therapy, hypoxic-hyperoxytherapy, hydrogen therapy and their combined use) to activate stress-limiting mechanisms and manifestations of professional burnout in medical professionals. MATERIALS AND METHODS: The research was conducted on the basis of the Scientific and Clinical Center 1 of the Russian National Research Center named after B.V. Petrovsky Academy with the participation of 175 patients from among the medical staff aged 30 to 60 years (25 of them without signs of professional burnout syndrome) and a group of somatic healthy non-medical workers. By the method of simple fixed randomization, patients with this syndrome were divided into 6 groups: control (n=25), comparison groups 1-4 (n=25 each) and main (n=25). Patients of all groups received a course of physical exercises and psychological correction. For the control group, this type of correction was exhaustive. In comparison group 1, an additional course of general air cryotherapy was performed; comparison group 2 additionally received a course of general magnetic therapy procedures; comparison group 3 additionally received a course of hypoxic-hyperoxytherapy; comparison group 4 additionally received a course of hydrogen therapy; in the main group, patients received a course of complex effects of therapeutic physical factors. The study design provided for a double examination of patients in all groups using the MBI questionnaire, the Spielberger-Hanin test and the Beck scale, as well as biochemical and hormonal stress markers. RESULTS: Individual signs of professional burnout syndrome may appear in medical professionals who have not yet verified this syndrome. At the same time, in its presence, the formation of pathological correlational pleiades is noted, integrating the relationship of the emotional and psychological parameters of this syndrome with indicators of oxidative stress and hormonal regulation of metabolic and energy homeostasis. The use of physiotherapeutic factors of various nature in patients with occupational burnout syndrome has made it possible to establish their effectiveness. Less pronounced changes were noted in the control group with the use of physical exercises and psychocorrection. Additional course application of therapeutic physiotherapeutic procedures in the monopharmaceutical mode (general air cryotherapy, general magnetic therapy, hypoxic-hyperoxytherapy and hydrogen therapy;) This was accompanied by an increase in the positive dynamics of the estimated indicators by 12-38%. The complex use of all physiotherapeutic effects, implemented in the main group, caused the development of the most pronounced corrective effect. CONCLUSION: The use of non-medicinal technologies makes it possible to achieve high efficiency in terms of activation of stress-limiting body systems and sanogenetic processes in medical workers with occupational burnout syndrome. The maximum corrective effect, manifested in the complex application of physiotherapeutic factors, is due to the realization of the additive supra-additive effect of the interaction of their therapeutic potentials.", "conclusion": "The use of non-medicinal technologies makes it possible to achieve high efficiency in terms of activation of stress-limiting body systems and sanogenetic processes in medical workers with occupational burnout syndrome. The maximum corrective effect, manifested in the complex application of physiotherapeutic factors, is due to the realization of the additive supra-additive effect of the interaction of their therapeutic potentials." }, { "pmid": "41376217", "year": 2025, "title": "Four-dimensional data independent acquisition proteomics and metabolomics reveal mechanisms of hydrogen-rich water at Zusanli (ST36) point against triple-negative breast cancer in mice.", "title_en": null, "title_de": "Vierdimensionale datenunabhängige Akquisitions-Proteomik und -Metabolomik enthüllen Mechanismen von wasserstoffreichem Wasser am Zusanli-Punkt (ST36) gegen dreifach-negativen Brustkrebs bei Mäusen", "journal": "Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan", "authors": "Jingxuan et al.", "author_search": "jingxuan jingxuan", "doi": "10.19852/j.cnki.jtcm.20250929.002", "doi_url": "https://doi.org/10.19852/j.cnki.jtcm.20250929.002", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41376217/", "url": "https://h2medicine.org/studies/study-jingxuan-2025-four-dimensional-data-independent/", "methods": [ "saline-iv", "drinking-hrw" ], "indications": [ "cancer", "joints-rheumatology" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Jingxuan — Four-dimensional Data Independent Acquisition Proteomics and Metabolomics Reveal Mechanisms of Hydrogen-rich Water at Zusanli (ST36) Point against Triple-negative Breast Cancer in Mice", "summary": "Injecting hydrogen-rich water into the Zusanli acupuncture point (ST36) significantly inhibited tumour growth and enhanced cancer-cell apoptosis in a mouse model of triple-negative breast cancer, according to this animal study combining proteomics and metabolomics. The approach modulated immune-related signalling pathways — including T helper cell differentiation — and metabolic routes involving galactose and fructose. (Journal of Traditional Chinese Medicine, 2025.)", "assessment": "This is a mouse study — results cannot be transferred to humans. The multi-omics methodology is rigorous, but the combination of H₂ and acupoint injection as a treatment makes it impossible to attribute effects to H₂ alone. Triple-negative breast cancer is a serious condition; no conclusions about human treatment can be drawn from this preclinical work. The study is scientifically interesting as a mechanistic exploration, but clinical relevance is speculative at this stage.", "abstract": "OBJECTIVE: To develop a safe and effective green therapy for triple-negative breast cancer, this study combines hydrogen-rich water with acupuncture point injection, and finds that it can prevent tumor growth and minimize cancer metastasis. METHODS: After 21 d of hydrogen rich water injection treatment on 4T1 (mouse breast cancer cells) xenograft mice, in order to systematically identify differentially expressed proteins in tumor samples between the model group and the Zusanli (ST36) group injected with hydrogen rich water at acupoints, with a focus on functional proteins or signaling pathways related to tumor occurrence and development, researchers conducted four-dimensional data independent acquisition (4D-DIA) proteomic analysis on tumor tissues. In order to further investigate the dynamic changes of metabolites after therapeutic intervention, researchers conducted liquid chromatography-tandem mass spectrometry untargeted metabolomics identification and analysis on mouse serum. The results of the joint proteomics-metabolomics analysis were validated using experimental methods such as immunofluorescence, Western blotting, and quantitative reverse transcription polymerase chain reaction detection. RESULTS: Injecting hydrogen-rich water into acupoints significantly inhibited tumor growth (P < 0.05). 4D-DIA proteomics and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses uncovered pathways such as T helper 1 cell (Th1) and T helper 2 cell (Th2) cell differentiation. The KEGG metabolic pathways identified in the metabolomics analysis included galactose metabolism along with fructose and mannose metabolism. Based on the combined proteomics and metabolomics analysis, the key pathways included the C-type lectin receptor signaling pathway. The major cancer-related differential proteins detected in Th1 and Th2 cell differentiation [interleukin 6 signal transducer, nuclear factor of activated T cells 4, recombinant mitogen activated protein kinase 10 (MAPK10), and MAPK11] were upregulated after the injection of hydrogen-rich water into the Zusanli (ST36) acupoint, whereas Linker for activation of T cells (Lat), signal transducer and activator of transcription 1, and protein kinase C, theta were downregulated. CONCLUSION: The injection of hydrogen-rich water into the Zusanli (ST36) acupoint effectively inhibited the hyperplasia of 4T1 BC cells and enhanced their apoptosis, potentially exerting a therapeutic effect through multiple pathways and targeting various sites.", "conclusion": "The injection of hydrogen-rich water into the Zusanli (ST36) acupoint effectively inhibited the hyperplasia of 4T1 BC cells and enhanced their apoptosis, potentially exerting a therapeutic effect through multiple pathways and targeting various sites." }, { "pmid": "41330217", "year": 2025, "title": "The Rieske iron-sulfur protein is a primary target of molecular hydrogen.", "title_en": null, "title_de": "Das Rieske-Eisen-Schwefel-Protein ist ein primäres Ziel von molekularem Wasserstoff", "journal": "Redox biology", "authors": "Negishi et al.", "author_search": "negishi negishi", "doi": "10.1016/j.redox.2025.103952", "doi_url": "https://doi.org/10.1016/j.redox.2025.103952", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41330217/", "url": "https://h2medicine.org/studies/study-negishi-2025-rieske-iron-sulfur-protein/", "methods": [ "unspecified" ], "indications": [ "liver", "sports-exercise" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Negishi — The Rieske Iron-sulfur Protein Is a Primary Target of Molecular Hydrogen", "summary": "Molecular hydrogen is not merely a passive free-radical scavenger — it actively targets a specific mitochondrial protein called the Rieske iron-sulfur protein (RISP), a new finding that could help explain H₂'s wide-ranging and sometimes paradoxical biological effects. This in-vitro and mouse liver study demonstrates that H₂ suppresses the electron transport chain and triggers a mitochondrial stress response within minutes. (Redox Biology, 2025.)", "assessment": "This is a mechanistically important in-vitro and animal (mouse liver) study — not a human clinical study. The identification of RISP as a primary H₂ target is a novel, testable hypothesis that, if replicated, would substantially advance understanding of hydrogen biology. The study is rigorous in its cell and tissue experiments. However, it does not demonstrate therapeutic benefit in any disease context, and the physiological consequences of RISP degradation require careful further investigation. This work is relevant to researchers; clinical implications remain to be determined.", "abstract": "The mechanisms underlying the biomedical effects of molecular hydrogen (H2) remain poorly understood and are often attributed to its selective reduction of hydroxyl radicals, based on the long-held notion that H2 is biologically inert. We demonstrate that H2 is biologically active, specifically targeting the Rieske iron-sulfur protein (RISP). We first observed that H2 induces the mitochondrial unfolded protein response (UPRmt) in cultured cells exposed to H2 and in mouse liver after H2 water administration. H2 suppressed electron transport chain complex III activity in mouse liver homogenates to 78.5 % within 2 min. Given the evolutionary link with hydrogenases, we examined RISP as a potential target of H2. We found that H2 promotes RISP degradation within 1 h in cultured cells by activating mitochondrial Lon peptidase 1 (LONP1). Loss of RISP and subsequent UPRmt induction may explain the pleiotropic and paradoxical effects of H2. These findings identify RISP as a primary target of H2, demonstrating that H2 is biologically active as a signaling molecule.", "conclusion": "Loss of RISP and subsequent UPRmt induction may explain the pleiotropic and paradoxical effects of H2. These findings identify RISP as a primary target of H2, demonstrating that H2 is biologically active as a signaling molecule." }, { "pmid": "41204320", "year": 2025, "title": "Hydrogen's Feasibility and Safety as a Therapy in Extracorporeal Cardiopulmonary Resuscitation (Hydrogen-FAST): study protocol for a trial of inhaled hydrogen gas as an adjunctive therapy in refractory cardiac arrest.", "title_en": null, "title_de": "Hydrogen-FAST: Studienprotokoll für inhaliertes Wasserstoffgas als adjunktive Therapie bei refraktärem Herzstillstand (ECPR)", "journal": "Trials", "authors": "Habet et al.", "author_search": "habet habet", "doi": "10.1186/s13063-025-09217-7", "doi_url": "https://doi.org/10.1186/s13063-025-09217-7", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41204320/", "url": "https://h2medicine.org/studies/study-habet-2025-feasibility-extracorporeal-cardiopulmonary-resuscitation/", "methods": [ "inhalation" ], "indications": [ "liver", "neurology", "cardiovascular", "respiratory", "fundamentals-safety" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2025 · Habet et al. — Hydrogen-FAST: Study Protocol for Inhaled Hydrogen Gas as Adjunctive Therapy in Refractory Cardiac Arrest (ECPR)", "summary": "The Hydrogen-FAST trial is a phase 1 multicenter randomised controlled trial investigating whether inhaled 2 % hydrogen gas, delivered continuously for 72 hours during extracorporeal cardiopulmonary resuscitation (ECPR), is feasible and safe in patients with refractory cardiac arrest and underlying heart disease. This publication describes the study protocol — results are pending. (Trials, 2025.)", "assessment": "This is a study protocol publication — no efficacy results yet. Its scientific value is the transparent pre-registration of methodology for a high-stakes clinical context (ECPR + ischaemia-reperfusion injury) where H₂ has strong preclinical support. What to watch: the feasibility endpoint (≥ 90 % H₂ delivery time) is demanding given the technical complexity of ECPR; congenital heart disease patients are a heterogeneous population; sample size (n = 53) is appropriate for a safety/feasibility trial only. If phase 1 results are positive, a properly powered efficacy trial will be needed. The ECMO-circuit delivery of H₂ is technically innovative and its safety in this context is precisely what Hydrogen-FAST is designed to establish.", "abstract": "BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) improves survival for patients experiencing refractory cardiac arrest but is often associated with severe ischemia-reperfusion injury (IRI). Hydrogen gas (H2) has demonstrated promising preclinical efficacy in reducing IRI. The Hydrogen-FAST trial investigates the feasibility and safety of inhaled hydrogen gas as an adjunctive therapy during ECPR in patients with congenital heart disease (CHD). METHODS: This phase 1 multicenter randomized controlled trial enrolls patients of any age undergoing ECPR due to refractory cardiac arrest associated with underlying cardiac morbidity. Due to the emergent nature of ECPR events, the trial leverages an Exception from Informed Consent enrollment process. Fifty-three participants will be randomized to standard care or standard care plus inhaled 2% H2 gas delivered continuously for 72 h via mechanical ventilator and extracorporeal membrane oxygenation (ECMO) circuit. Primary endpoints include feasibility, measured as the percentage of the first 72 h post-arrest in which hydrogen is successfully administered, with feasibility defined as a mean percentage of ≥90%, and safety, evaluated through incidence rates of treatment-related serious adverse events (SAEs). Secondary endpoints examine clinical outcomes including survival to discharge, ICU length of stay, functional status at 6 months, neurologic function, and markers of ischemic injury. DISCUSSION: The Hydrogen-FAST trial will provide essential data on the feasibility and safety of H2 administration during ECPR, informing larger efficacy studies and potential broader clinical use in critical care settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT05574296. Registered on October 6, 2022. https://clinicaltrials.gov/study/NCT05574296 .", "conclusion": "Registered on October 6, 2022. https://clinicaltrials.gov/study/NCT05574296 ." }, { "pmid": "41176039", "year": 2025, "title": "Hydrogen enhanced photothermal therapy for redox-regulated tumor apoptosis and immune reprogramming.", "title_en": null, "title_de": "Wasserstoffverstärkte photothermische Therapie für redox-regulierte Tumorapoptose und Immun-Reprogrammierung", "journal": "Acta biomaterialia", "authors": "Chu et al.", "author_search": "chu chu", "doi": "10.1016/j.actbio.2025.10.059", "doi_url": "https://doi.org/10.1016/j.actbio.2025.10.059", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41176039/", "url": "https://h2medicine.org/studies/study-chu-2025-enhanced-photothermal-redox-regulated/", "methods": [ "unspecified" ], "indications": [ "neurology", "cancer", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Chu — Hydrogen Enhanced Photothermal Therapy for Redox-regulated Tumor Apoptosis and Immune Reprogramming", "summary": "A novel nanomaterial platform combines hydrogen release with near-infrared photothermal heating to simultaneously destroy tumour cells and protect immune cells — demonstrating, for the first time, that H₂ can act as both a pro-oxidant in cancer cells and an antioxidant protector in immune cells within the same tumour environment. This animal study reports enhanced tumour killing and immune activation. (Acta Biomaterialia, 2025.)", "assessment": "This is a preclinical animal study — all results are from mouse tumour models; no human data are presented. The nanosheet platform is experimental and would require extensive safety, manufacturing, and clinical testing before any human application. The dual redox-switching concept (pro-oxidant in tumour cells, antioxidant in immune cells) is mechanistically novel and scientifically important if replicated. However, mouse tumour models frequently overestimate treatment efficacy. This work is a contribution to basic cancer nanomedicine research, not a clinical advancement.", "abstract": "Photothermal-catalysis enables controlled hydrogen release and redox modulation, with applications in biomedical therapy. Despite growing interest in hydrogen therapy, its effects on immune cells within the tumor microenvironment (TME) remain insufficiently elucidated, specifically regarding selective redox modulation and immune activation. Herein, we present H atoms stabilize the rhodium palladium bimetallene (RhPd-H) nanosheets as a hydrogen-loaded photothermal-catalytic platform with NIR-triggered release for targeted redox modulation in TME. Upon NIR irradiation, RhPd-H serves as a dual-source of hydrogen and localized heat, inducing reactive oxygen species (ROS) bursts that selectively disrupt tumor redox homeostasis, leading to apoptosis of tumor cells. Synergistically, hydrogen scavenges ROS in immune cells, protecting them from oxidative stress and further promoting dendritic cell maturation, T-cell activation, and macrophage polarizaion for exerting anti-tumor effects. Experimental data reveals the synergy of hydrogen-photothermal therapy in ablating tumors and reprograming the immunosuppressive TME, as evidenced by enhanced antigen presentation, amplified T-cell infiltration and systemic anti-tumor memory responses. Particularly, we report the novel finding that hydrogen performs both protective and activating effects on immune cells, which to our knowledge has not been previously documented, revealing a veil of mystery of hydrogen therapy. By integrating hydrogen-mediated redox editing and immunomodulation, this work establishes a paradigm-shifting strategy for precise tumor therapy. STATEMENT OF SIGNIFICANCE: This work unveils a paradigm-shifting duality of hydrogen (H₂) within the tumor microenvironment: simultaneously acting as a pro-oxidative inducer of reactive oxygen species (ROS) bursts in tumor cells while serving as a protective antioxidant and immunomodulator in immune cells. Under NIR irradiation, H₂ released from hydrogen-stabilized rhodium-palladium bimetallene (RhPd-H) nanosheets synergizes with photothermal energy to disrupt redox homeostasis and trigger selective apoptosis in tumors. Concurrently, in immune cells, H₂ scavenges photothermal-induced ROS-shielding them from oxidative damage while activating dendritic cell maturation, cytotoxic T-cell infiltration, and macrophage polarization toward antitumor phenotypes. This cell-contextual redox switching not only ablates tumors directly but also reprograms the immunosuppressive microenvironment, revealing an unprecedented biological mechanism for hydrogen therapy and establishing differential redox editing as a transformative strategy for precision cancer treatment.", "conclusion": "Concurrently, in immune cells, H₂ scavenges photothermal-induced ROS-shielding them from oxidative damage while activating dendritic cell maturation, cytotoxic T-cell infiltration, and macrophage polarization toward antitumor phenotypes. This cell-contextual redox switching not only ablates tumors directly but also reprograms the immunosuppressive microenvironment, revealing an unprecedented biolo" }, { "pmid": "41167690", "year": 2025, "title": "A Case Report of Adjuvant Molecular Hydrogen Therapy in Refractory Rheumatoid Arthritis With Atlantoaxial Subluxation.", "title_en": null, "title_de": "Ein Fallbericht über adjuvante Therapie mit molekularem Wasserstoff bei refraktärer rheumatoider Arthritis mit atlantoaxialer Subluxation", "journal": "In vivo (Athens, Greece)", "authors": "Ren et al.", "author_search": "ren ren", "doi": "10.21873/invivo.14166", "doi_url": "https://doi.org/10.21873/invivo.14166", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41167690/", "url": "https://h2medicine.org/studies/study-ren-2025-adjuvant-refractory-rheumatoid-arthritis/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise", "neurology", "skin-aging", "joints-rheumatology", "immune-system", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2025 · Ren et al. — A Case Report of Adjuvant Molecular Hydrogen Therapy in Refractory Rheumatoid Arthritis With Atlantoaxial Subluxation", "summary": "An 85-year-old woman with long-standing treatment-refractory rheumatoid arthritis — complicated by the rare and neurologically dangerous atlantoaxial subluxation — received molecular hydrogen therapy as an adjuvant, which was associated with notable fatigue reduction and immunological shifts, though her overall disease trajectory remained grave. (In Vivo, 2025.)", "assessment": "Single case report with validated fatigue outcome measure (BFI-T) — a methodological strength over purely qualitative descriptions. The clinical context (very elderly, multiple comorbidities, concurrent steroids and hydroxychloroquine, fatal outcome from disease complications) makes it impossible to isolate hydrogen's contribution. Limitations: n = 1, terminal disease trajectory, concurrent background medication, no control, atlantoaxial subluxation and subsequent death confound long-term outcome interpretation. The fatigue benefit is the most patient-relevant finding and deserves follow-up in a controlled fatigue-focused trial in RA.", "abstract": "BACKGROUND/AIM: Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting synovial joints, often causing to joint destruction and systemic comorbidities. Cervical spine involvement, especially atlantoaxial subluxation (AAS), can lead to spinal cord compression and neurological deficits. While disease-modifying antirheumatic drugs (DMARDs) are standard therapy, intolerance to agents like methotrexate (MTX) in elderly or comorbid patients limits options. Molecular hydrogen, with antioxidant and anti-inflammatory properties, has emerged as a potential adjuvant in autoimmune diseases. This case report describes an elderly woman with long-standing, treatment-refractory RA and severe cervical spine disease who received molecular hydrogen therapy, highlighting immunological changes, clinical outcomes, and challenges in managing RA with complex comorbidities. CASE REPORT: An 85-year-old Taiwanese woman with long-standing rheumatoid arthritis (2010 American College of Rheumatology/European League Against Rheumatism criteria) and multiple comorbidities discontinued methotrexate in 2016 due to pancytopenia. Her RA was managed with oral steroids and hydroxychloroquine, but she had recurrent hospitalizations for flares with multiple joint pain. Molecular hydrogen therapy was initiated in June 2023 as an adjuvant treatment. Fatigue, assessed using the Taiwan Brief Fatigue Inventory (BFI-T), improved notably across multiple domains, accompanied by dynamic changes in immune cell populations suggesting immunomodulatory effects. During this admission, atlantoaxial subluxation was diagnosed, fulfilling surgical criteria; however, the patient and her family declined surgery due to risk and prognosis, opting for palliative care until her death. CONCLUSION: This case highlights the potential immunomodulatory benefits of molecular hydrogen as an adjuvant therapy in rheumatoid arthritis. Although clinical and immunological improvements were observed, larger studies with longer follow-up are needed. It also illustrates severe cervical spine involvement, atlantoaxial subluxation, underscoring the complexity and neurological risks of advanced RA.", "conclusion": "This case highlights the potential immunomodulatory benefits of molecular hydrogen as an adjuvant therapy in rheumatoid arthritis. Although clinical and immunological improvements were observed, larger studies with longer follow-up are needed. It also illustrates severe cervical spine involvement, atlantoaxial subluxation, underscoring the complexity and neurological risks of advanced RA." }, { "pmid": "41167678", "year": 2025, "title": "Dynamic Immunomodulation by Hydrogen Capsule Therapy in SLE-associated Pulmonary Arterial Hypertension: A Case Report.", "title_en": null, "title_de": "Dynamische Immunmodulation durch Wasserstoff-Kapseltherapie bei SLE-assoziierter pulmonalarterieller Hypertonie: Ein Fallbericht", "journal": "In vivo (Athens, Greece)", "authors": "Liu et al.", "author_search": "liu liu", "doi": "10.21873/invivo.14165", "doi_url": "https://doi.org/10.21873/invivo.14165", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41167678/", "url": "https://h2medicine.org/studies/study-liu-2025-dynamic-immunomodulation-capsule-sle/", "methods": [ "unspecified" ], "indications": [ "cardiovascular", "respiratory", "immune-system", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2025 · Liu et al. — Dynamic Immunomodulation by Hydrogen Capsule Therapy in SLE-associated Pulmonary Arterial Hypertension: A Case Report", "summary": "A 45-year-old woman with SLE-associated pulmonary arterial hypertension showed a striking biphasic immunological response to hydrogen capsule therapy: immune activation markers (KLRG1+ T cells, CD39+Helios- regulatory T cells, regulatory B cells) were suppressed during therapy but rebounded after stopping — suggesting a transient immunosuppressive effect followed by regulatory rebalancing. (In Vivo, 2025.)", "assessment": "Single case report, but with an unusually informative longitudinal immunophenotyping design that captures a before-during-after time course. The biphasic pattern is the genuinely novel contribution and generates a testable hypothesis for future pharmacodynamic studies. Limitations: n = 1, SLE-PAH is a rare and severe condition making generalisation difficult, H₂ delivery route unspecified, no haemodynamic endpoints reported, clinical improvement qualitative only. See also companion report PMID 41482388 from the same group for context.", "abstract": "BACKGROUND/AIM: Pulmonary arterial hypertension (PAH) is a severe complication of systemic lupus erythematosus (SLE), marked by vascular remodeling, immune dysregulation, and progressive right heart failure. Molecular hydrogen therapy, a selective antioxidant and anti-inflammatory agent, has the capacity to modulate immune responses in these autoimmune disease patients. This case report details the clinical improvement in an SLE patient with PAH after starting adjunctive hydrogen capsule therapy, highlighting its potential as a novel approach for this challenging complication. CASE REPORT: A 45-year-old Taiwanese woman with SLE-PAH who received hydrogen capsule therapy, during which serial immunophenotyping revealed dynamic changes in T cell exhaustion markers, regulatory T cell (Treg) subsets, and regulatory B cells (Breg). Notably, KLRG1+ T cells and CD39+Helios- Tregs were suppressed during therapy but rebounded after cessation, suggesting transient immune suppressing followed by regulatory rebalancing. Bregs also showed a similar pattern, declining during therapy and recovering after discontinuation. CONCLUSION: These findings suggest a biphasic immunomodulatory effect of hydrogen therapy, that is, initially dampening immune activation, followed by a regulatory rebound after hydrogen therapy.", "conclusion": "These findings suggest a biphasic immunomodulatory effect of hydrogen therapy, that is, initially dampening immune activation, followed by a regulatory rebound after hydrogen therapy." }, { "pmid": "41083007", "year": 2025, "title": "Transdermal hydrogen therapy for psoriasis using cavity-embedded double-conical microneedles.", "title_en": null, "title_de": "Transdermale Wasserstofftherapie bei Psoriasis unter Verwendung von hohlraumeingebetteten doppelkonischen Mikronadeln", "journal": "Journal of controlled release : official journal of the Controlled Release Society", "authors": "Zhu et al.", "author_search": "zhu zhu", "doi": "10.1016/j.jconrel.2025.114313", "doi_url": "https://doi.org/10.1016/j.jconrel.2025.114313", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41083007/", "url": "https://h2medicine.org/studies/study-zhu-2025-transdermal-psoriasis-cavity-embedded/", "methods": [ "bath-topical" ], "indications": [ "liver", "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Zhu — Transdermal Hydrogen Therapy for Psoriasis Using Cavity-embedded Double-conical Microneedles", "summary": "A new microneedle patch delivers hydrogen directly through the skin into psoriatic tissue, where sustained H₂ release significantly outperformed a standard topical therapy (calcipotriol cream) in reducing oxidative damage, inflammation, and the hallmark skin thickening of psoriasis. This is an animal study in mice; no human data are available. (Journal of Controlled Release, 2025.)", "assessment": "This is an animal (mouse) study of an experimental drug-delivery device. The results cannot be applied to humans. The comparison with calcipotriol is an important design element, but mouse psoriasis models have well-known limitations in predicting human outcomes. MgH₂ in skin tissue is a novel material application that requires dedicated safety characterisation. The study makes a scientifically interesting engineering and mechanistic contribution; clinical relevance awaits controlled human trials.", "abstract": "Psoriasis remains clinically incurable due to its complex etiology. Topical immunosuppressive therapies offer limited effectiveness partly because of poor skin permeability, and can cause severe side effects. To address these challenges, we developed a novel transdermal hydrogen therapy that targets the mutually-reinforcing coupling between oxidative stress and inflammation in psoriasis. Specifically, we designed a double-conical microneedle with high loading capacity and effective skin penetration to efficiently deliver MgH2 powders, enabling the sustained release of molecular hydrogen within the skin tissue. This minimally invasive, self-administrable treatment significantly outperformed calcipotriol cream, a current standard topical therapy. The transdermal hydrogen therapy greatly relieved oxidative damages, pro-inflammatory cytokine expression, immune cell infiltration, and ultimately mitigated keratinocyte hyperproliferation and systemic symptoms. Furthermore, the mechanistic investigations provide valuable insights into psoriasis pathogenesis. More broadly, this study demonstrates a new solution for treating inflammatory skin diseases and a new strategy for microneedle-based transdermal therapeutic delivery.", "conclusion": "Furthermore, the mechanistic investigations provide valuable insights into psoriasis pathogenesis. More broadly, this study demonstrates a new solution for treating inflammatory skin diseases and a new strategy for microneedle-based transdermal therapeutic delivery." }, { "pmid": "41076526", "year": 2025, "title": "Spontaneous hydrogen-releasing nanoenzyme alleviates osteoarthritis via oxidative stress reduction and mitochondrial dysfunction reversal.", "title_en": null, "title_de": "Spontan wasserstofffreisetzendes Nanoenzym lindert Osteoarthritis durch Reduktion von oxidativem Stress und Umkehrung der mitochondrialen Dysfunktion", "journal": "Journal of nanobiotechnology", "authors": "Wang et al.", "author_search": "wang wang", "doi": "10.1186/s12951-025-03716-0", "doi_url": "https://doi.org/10.1186/s12951-025-03716-0", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41076526/", "url": "https://h2medicine.org/studies/study-wang-2025-spontaneous-releasing-nanoenzyme-alleviates/", "methods": [ "inhalation" ], "indications": [ "skin-aging", "joints-rheumatology", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Wang — Spontaneous Hydrogen-releasing Nanoenzyme Alleviates Osteoarthritis via Oxidative Stress Reduction and Mitochondrial Dysfunction Reversal", "summary": "A newly engineered nanoenzyme that spontaneously releases hydrogen gas alleviated osteoarthritis in animal experiments by reducing oxidative stress, restoring mitochondrial function, promoting the clearance of damaged mitochondria (mitophagy), and slowing cartilage degeneration. This is a preclinical animal study; results cannot be transferred to human patients. (Journal of Nanobiotechnology, 2025.)", "assessment": "This is a preclinical animal study — all results are from OA mouse models; no human data exist. The nanoenzyme platform is experimentally innovative but far from clinical translation. Osteoarthritis is a major unmet medical need, and this work contributes mechanistic insight into how H₂ could protect cartilage at the mitochondrial level. However, the fabrication complexity, biodistribution, and long-term safety of this system are entirely untested in humans. No treatment conclusions for patients can be drawn.", "abstract": "Osteoarthritis (OA), a chronic and degenerative joint disease, has become increasingly prevalent due to the aging population, posing a significant societal burden. However, despite progress, effective therapeutic options for osteoarthritis remain limited. In OA, chronic inflammation mediates a hypoxic microenvironment, leading to increased cellular energy demands. Over time, this causes mitochondrial dysfunction, favoring the accumulation of ROS, thereby perpetuating inflammation. Furthermore, reduced autophagy in aging chondrocytes hinder the clearance of damaged mitochondria, exacerbating oxidative stress. Herein, we have developed a simple and environmentally friendly strategy to fabricate hydrogen-releasing nanozymes (Se-HMPB@AB@COS) that spontaneously release hydrogen gas, effectively treating osteoarthritis through antioxidant, anti-inflammatory, and mitochondrial dysfunction reversal mechanisms. During the process of hydrogen therapy, small hydrogen molecules can readily penetrate mitochondria, specifically reducing the levels of •OH thereby protecting mitochondrial function. Our research further unveils that hydrogen therapy can effectively enhance mitophagy and delay chondrocyte senescence. In vivo, Se-HMPB@AB@COS encapsulated with chondroitin sulfate significantly promotes the synthesis of collagen II, inhibits the degradation of extracellular matrix, and reduces inflammatory factors. Overall, this study innovatively synthesized a hydrogen-releasing nanozyme, demonstrating its effectiveness in inhibiting oxidative stress, inflammation, promoting mitophagy and extracellular matrix synthesis, thereby reducing cartilage and mitochondrial damage, and delaying OA progression.", "conclusion": "In vivo, Se-HMPB@AB@COS encapsulated with chondroitin sulfate significantly promotes the synthesis of collagen II, inhibits the degradation of extracellular matrix, and reduces inflammatory factors. Overall, this study innovatively synthesized a hydrogen-releasing nanozyme, demonstrating its effectiveness in inhibiting oxidative stress, inflammation, promoting mitophagy and extracellular matrix sy" }, { "pmid": "41063273", "year": 2025, "title": "Biomechanical analysis of biodegradable magnesium, zinc, and polylactide pins for fixation of radial head fractures.", "title_en": null, "title_de": "Biomechanische Analyse biologisch abbaubarer Stifte aus Magnesium, Zink und Polylactid zur Fixierung von Radiusköpfchenfrakturen", "journal": "Journal of orthopaedic surgery and research", "authors": "Maier et al.", "author_search": "maier maier", "doi": "10.1186/s13018-025-06346-2", "doi_url": "https://doi.org/10.1186/s13018-025-06346-2", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41063273/", "url": "https://h2medicine.org/studies/study-maier-2025-biomechanical-analysis-biodegradable-magnesium/", "methods": [ "inhalation" ], "indications": [ "sports-exercise", "joints-rheumatology" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Maier — Biomechanical Analysis of Biodegradable Magnesium, Zinc, and Polylactide Pins for Fixation of Radial Head Fractures", "summary": "Biodegradable magnesium and zinc pins outperformed polylactide pins in laboratory biomechanical testing for radial head fracture fixation, with magnesium pins showing the highest stiffness and lowest fracture displacement. This in-vitro study on synthetic bone models compares three materials — but hydrogen gas formation from dissolving magnesium implants is flagged as a known concern requiring further investigation. (Journal of Orthopaedic Surgery and Research, 2025.)", "assessment": "This is an in-vitro biomechanical study on synthetic bone models — not a clinical or biological H₂ study. The connection to hydrogen is that magnesium implants produce H₂ gas during degradation, but this study does not investigate any therapeutic effect of that hydrogen. Its findings are relevant to orthopaedic implant materials research. Conclusions about H₂ as a therapy cannot be drawn from this work.", "abstract": "BACKGROUND: Biodegradable implants have raised constant interest for fixation of displaced radial head fractures due to avoiding implant removal and minimizing cartilage damage. Polylactide pins (PP) are frequently used in clinical practice, but inferior mechanical properties showed higher rates of secondary dislocation compared to metal implants. Magnesium pins (MP) provide superior stability but exhibit inconsistent resorption and relevant hydrogen gas formation. Recently, zinc pins (ZP) have emerged as a promising alternative, offering comparable mechanical strength with favourable biocompatibility. Since these implants have not been tested for specific fracture fixation, this study aims to evaluate their applicability in a validated Mason type II radial head fracture model. METHODS: Standardized Mason type II fractures were conducted in biomechanically validated composite radii, and fixed by using either two 2.0 mm MPs, ZPs, or PPs. Biomechanical testing included 10 cycles of transverse loading, 1,000 cycles of axial loading (15-50 N at 0.1 Hz), and load-to-failure testing (2 N/sec). Stability was assessed by stiffness (kN/mm) under axial and transverse loading, fracture displacement (mm) after 1,000 cycles, and failure load (N) at dislocation ≥ 2 mm. RESULTS: MPs demonstrated the highest primary stability, followed by ZPs and PPs under both transverse (PP: 0.36 ± 0.08 kN/mm vs. MP: 1.30 ± 0.31 kN/mm, p < .001; vs. ZP: 0.87 ± 0.33 kN/mm, p = .012) and axial loading (PP: 0.43 ± 0.10 kN/mm vs. MP: 1.25 ± 0.31 kN/mm, p < .001; vs. ZP: 0.77 ± 0.18 kN/mm, p = .035). Fracture displacement after 1,000 cycles was lower with MPs and ZPs than PPs (PP: 0.038 ± 0.009 mm vs. MP: 0.013 ± 0.003 mm, p < .001; vs. ZP: 0.022 ± 0.007 mm, p = .003). MPs (282 ± 26 N) showed the highest load-to-failure at 2 mm dislocation, followed by ZPs (261 ± 38 N) and PPs (215 ± 53 N) (PP vs. MP: p = .032; PP vs. ZP: p = .164; MP vs. ZP p = .650). CONCLUSION: In this biomechanical model of Mason type II radial head fractures, biodegradable magnesium and zinc pins demonstrated superior primary stability and load-bearing capacity compared to polylactide implants. MP showed the highest stiffness and lowest fracture displacement, while ZP achieved comparable performance in fracture stabilization. These findings suggest that zinc-based implants could offer a clinically valuable alternative for radial head fracture fixation, potentially reducing complications seen with the other implants. Further in-vivo, cadaveric, and clinical studies are necessary to confirm long-term outcomes and biological integration. LEVEL OF EVIDENCE: Basic Science Study.", "conclusion": "In this biomechanical model of Mason type II radial head fractures, biodegradable magnesium and zinc pins demonstrated superior primary stability and load-bearing capacity compared to polylactide implants. MP showed the highest stiffness and lowest fracture displacement, while ZP achieved comparable performance in fracture stabilization. These findings suggest that zinc-based implants could offer a clinically valuable alternative for radial head fracture fixation, potentially reducing complicati" }, { "pmid": "41043278", "year": 2025, "title": "Hydrogen-rich gas enhances mitochondrial membrane potential and respiratory function recovery in Caco-2 cells post-ischemia-reperfusion injury.", "title_en": null, "title_de": "Wasserstoffreiches Gas verstärkt das mitochondriale Membranpotenzial und die Erholung der Atmungsfunktion in Caco-2-Zellen nach Ischämie-Reperfusionsschaden", "journal": "Biochemical and biophysical research communications", "authors": "Seya et al.", "author_search": "seya seya", "doi": "10.1016/j.bbrc.2025.152753", "doi_url": "https://doi.org/10.1016/j.bbrc.2025.152753", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41043278/", "url": "https://h2medicine.org/studies/study-seya-2025-enhances-mitochondrial-membrane-respiratory/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise", "respiratory", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Seya — Hydrogen-rich Gas Enhances Mitochondrial Membrane Potential and Respiratory Function Recovery in Caco-2 Cells Post-ischemia-reperfusion Injury", "summary": "Hydrogen-rich gas restored mitochondrial function in human intestinal cells (Caco-2) after simulated ischemia-reperfusion injury, improving ATP production, mitochondrial membrane potential, and oxygen consumption while reducing cell death signals. This in-vitro study in cultured cells builds on prior animal work and proposes that H₂ acts upstream of the hypoxia-driven HIF1α signalling pathway. (Biochemical and Biophysical Research Communications, 2025.)", "assessment": "This is an in-vitro cell study — no animal or human data are included. The H₂ concentration used (99%) is experimentally maximal and not translatable to clinical settings. The study advances mechanistic understanding of how H₂ may protect mitochondria from I/R injury, specifically by modulating HIF1α/PDK1 signalling. This is cell biology, not a clinical proof of concept. Further animal studies and then controlled human trials would be required before any clinical conclusions.", "abstract": "BACKGROUND: Ischemia-reperfusion (I/R) injury induces oxidative stress, leading to damage in highly susceptible intestinal tissues. Molecular hydrogen (H2) has shown therapeutic potential in I/R injuries, with our prior research showing its efficacy in improving outcomes in rat intestinal transplantation models. However, its impact on mitochondrial function remain insufficiently understood. This study aims to elucidate how H2 modulates mitochondrial function impaired by I/R injury. METHODS: To assess the effects of H2 on I/R injury, cells were divided into three groups: a control group, a hypoxic group (99 % N2, 1 % O2, without H2 for 3, 6, or 24 h), and a hypoxic-H2 group (99 % H2, 1 % O2, for the same durations). After treatment, cells were reoxygenated under normoxic conditions (21 % O2) for 1, 2, 4, or 6 h. Mitochondrial membrane potential, oxygen consumption, and ATP production were measured. Reactive oxygen species production and apoptotic and metabolic regulators were also assessed. RESULTS: H2 markedly promoting mitochondrial recovery following I/R injury, by enhancing ATP production, restoring mitochondrial membrane potential, and improving oxygen consumption. It also reduced ROS levels and suppressed pro-apoptotic signaling. Notably, H2 suppressed the expression of HIF1α and PDK1, suggesting that H2 may act upstream of hypoxia-driven signaling pathways. These changes promoted oxidative phosphorylation and overall cellular function during reperfusion. CONCLUSIONS: Our findings reveal that H2 therapy supports mitochondrial function, suppresses ROS, and modulates hypoxia-driven pathways in I/R injury. These insights advance the understanding of H2's potential in addressing I/R injury and provide a foundation for its application in other hypoxia-related conditions.", "conclusion": "Our findings reveal that H2 therapy supports mitochondrial function, suppresses ROS, and modulates hypoxia-driven pathways in I/R injury. These insights advance the understanding of H2's potential in addressing I/R injury and provide a foundation for its application in other hypoxia-related conditions." }, { "pmid": "41013628", "year": 2025, "title": "Research on the inhibitory effect of hydrogen gas on ovarian cancer and potential mechanisms.", "title_en": null, "title_de": "Forschung zur hemmenden Wirkung von Wasserstoffgas auf Eierstockkrebs und mögliche Mechanismen", "journal": "European journal of medical research", "authors": "Yin et al.", "author_search": "yin yin", "doi": "10.1186/s40001-025-03111-3", "doi_url": "https://doi.org/10.1186/s40001-025-03111-3", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/41013628/", "url": "https://h2medicine.org/studies/study-yin-2025-research-inhibitory-ovarian-cancer/", "methods": [ "inhalation" ], "indications": [ "cancer", "womens-health" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Yin — Research on the Inhibitory Effect of Hydrogen Gas on Ovarian Cancer and Potential Mechanisms", "summary": "Hydrogen gas inhibited ovarian cancer cell viability, migration, and invasion, promoted apoptosis, and reduced tumour size in both cell and animal experiments by modulating oxidative stress markers and suppressing key oncogenic proteins (HIF-1α, NF-κB p65). This preclinical study in SKOV3 cells and mice provides mechanistic insight into hydrogen's anti-tumour potential against one of the deadliest gynaecological cancers. (European Journal of Medical Research, 2025.)", "assessment": "This is a preclinical study (cell lines + mouse model) — no human data exist. Ovarian cancer is a serious illness; this research does not constitute evidence that hydrogen treats ovarian cancer in humans. The mechanistic findings are scientifically interesting and consistent with other preclinical H₂-oncology work. Independent replication and progression through animal toxicology and eventually controlled clinical trials would be required before any clinical application.", "abstract": "Ovarian cancer is one of the most fatal malignancies in women worldwide; current treatment approaches still struggle to effectively control tumor progression. Therefore, it is imperative to explore novel and more effective therapeutic approaches. Hydrogen shows promise as a novel adjuvant therapy, offering new perspectives for ovarian cancer treatment. This study primarily investigates the effects of hydrogen on SKOV3 ovarian cancer cell line viability, apoptosis, migration, invasion, MDA, SOD levels, and key regulatory proteins through experiments including CCK-8, flow cytometry, scratch assay, Transwell assay, immunofluorescence, Western blot, and ELISA. HE staining, TUNEL, immunohistochemistry, immunofluorescence, Western blot, and ELISA were used to verify the antitumor effects of hydrogen in vivo. The results showed that hydrogen inhibited cell viability, migration, and invasion, promoted apoptosis, and induced G1/G2 phase arrest in SKOV3 cells. Additionally, hydrogen promoted ROS production, downregulated the expression of HIF-1α, NF-κB p65, and P-p65 proteins, decreased SOD levels, and increased MDA levels. The results of animal experiments showed that the tumor weight and volume in the hydrogen group were significantly smaller than those in the control group. At the same time, hydrogen promoted tumor cell apoptosis, reduced the levels of angiogenesis markers within the tumor, lowered the protein levels of HIF-1α and p65, increased MDA levels, and decreased SOD levels. Hydrogen provides a new approach for the treatment of ovarian cancer.", "conclusion": "At the same time, hydrogen promoted tumor cell apoptosis, reduced the levels of angiogenesis markers within the tumor, lowered the protein levels of HIF-1α and p65, increased MDA levels, and decreased SOD levels. Hydrogen provides a new approach for the treatment of ovarian cancer." }, { "pmid": "40976279", "year": 2025, "title": "Hierarchical ROS-scavenging platform breaks vicious cycle of stem cell senescence, angiogenesis arrest, and immune dysregulation in diabetic wounds.", "title_en": null, "title_de": "Hierarchische ROS-eliminierende Plattform durchbricht den Teufelskreis aus Stammzellseneszenz, Angiogenese-Stillstand und Immundysregulation bei diabetischen Wunden.", "journal": "Journal of controlled release : official journal of the Controlled Release Society", "authors": "Wang et al.", "author_search": "wang wang", "doi": "10.1016/j.jconrel.2025.114247", "doi_url": "https://doi.org/10.1016/j.jconrel.2025.114247", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40976279/", "url": "https://h2medicine.org/studies/study-wang-2025-hierarchical-ros-scavenging-platform/", "methods": [ "inhalation" ], "indications": [ "diabetes", "cardiovascular", "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Wang — Hierarchical ROS-scavenging platform breaks vicious cycle of stem cell senescence, angiogenesis arrest, and immune dysregulation in diabetic wounds.", "summary": "Diabetic chronic wounds are driven by a self-reinforcing cycle of oxidative stress, stem cell ageing, impaired blood-vessel growth, and immune imbalance. Researchers embedded calcium hydride (CaH₂) nanoparticles in a microneedle patch: upon contact with wound fluid, the particles release sustained molecular hydrogen (H₂) and calcium ions (Ca²⁺), breaking this destructive cascade. In diabetic mice, the system accelerated wound closure, promoted new vessel formation, and reduced inflammatory infiltration. (Journal of Controlled Release, 2025.)", "assessment": "An innovative preclinical proof-of-concept for a combined H₂/Ca²⁺ microneedle device targeting the complex pathology of diabetic wounds. The multi-pathway rationale is well-reasoned and the mouse data are encouraging. Critical limitation: this is an animal study — results cannot be directly extrapolated to humans. Diabetic wound healing in rodents differs substantially from the human clinical situation (skin anatomy, wound chronicity, co-morbidity burden). No toxicity or immune-response data in humans exist. Clinical translation requires safety studies, stable manufacturing of CaH₂ nanomaterials, and ultimately randomised controlled trials. Promising direction, but not yet evidence for human benefit.", "abstract": "Diabetic chronic wounds represent a formidable clinical challenge, driven by a pathological vicious cycle of reactive oxygen species (ROS)-induced oxidative stress, stem cell senescence, angiogenesis arrest, and immune dysregulation. Herein, we developed a hierarchical ROS-scavenging platform integrating nanoscale calcium hydride (CaH₂) within a microneedle (MN) patch to disrupt this degenerative cascade. Upon dissolution in wound exudate, CaH₂ nanoparticles react with water to generate sustained release of hydrogen gas (H₂) and calcium ions (Ca2+). The liberated H₂ directly neutralizes cytotoxic ROS, thereby reversing stem cell senescence and restoring their paracrine secretion of pro-angiogenic factors, while concomitantly reprogramming macrophages toward pro-regenerative M2 phenotypes. Simultaneously, Ca2+ synergizes with H₂ to activate endothelial cell migration and tubulogenesis, fostering robust vascular network formation. By concurrently resolving oxidative stress, stem cell senescence, angiogenesis arrest, and immune dysregulation, the CaH₂-MN system breaks the vicious cycle to reshape the wound microenvironment into a pro-regenerative state. In diabetic murine models, this approach accelerated wound closure, enhanced neovascularization, and reduced inflammatory infiltration. This multiscale intervention paradigm provides a blueprint for intercepting pathological cascades in diabetic wounds.", "conclusion": "In diabetic murine models, this approach accelerated wound closure, enhanced neovascularization, and reduced inflammatory infiltration. This multiscale intervention paradigm provides a blueprint for intercepting pathological cascades in diabetic wounds." }, { "pmid": "40931918", "year": 2025, "title": "Nanobiocatalyst-Driven Spatiotemporal Hydrogen Delivery Induces Dormancy Potentiated Catalytic Tumor Therapy.", "title_en": null, "title_de": "Nanobiokatalysator-gesteuerte raumzeitliche Wasserstoffabgabe induziert dormanz-potenzierte katalytische Tumortherapie.", "journal": "ACS nano", "authors": "Cao et al.", "author_search": "cao cao", "doi": "10.1021/acsnano.5c10754", "doi_url": "https://doi.org/10.1021/acsnano.5c10754", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40931918/", "url": "https://h2medicine.org/studies/study-cao-2025-nanobiocatalyst-driven-spatiotemporal-delivery/", "methods": [ "drinking-hrw" ], "indications": [ "liver", "cancer", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Cao — Nanobiocatalyst-Driven Spatiotemporal Hydrogen Delivery Induces Dormancy Potentiated Catalytic Tumor Therapy.", "summary": "Colorectal cancer cells can be pushed into a dormant, non-dividing state by molecular hydrogen (H₂) — and this dormancy makes them far more vulnerable to oxidative attack. Researchers engineered a platinum-containing metal-organic framework that generates H₂ on demand using light, combined with a drug (5-ASA) that locks tumour cells in dormancy and blocks the NF-κB survival pathway. In three different animal tumour models, the combined approach achieved strong anti-tumour effects. (ACS Nano, 2025.)", "assessment": "A highly innovative but entirely preclinical study exploring H₂ as a tumour-dormancy inducer combined with catalytic cancer therapy. The multiomics approach and three-model validation are genuine methodological strengths. However, this is animal research — no human data exist, and results cannot be directly transferred to patients. Key translational barriers include: safe delivery of the platinum-MOF nanomaterial to human tumours, dependence on external light activation (limiting tumour accessibility), and the unresolved question of whether inducing widespread dormancy in a patient context is safe and controllable. The concept is compelling and warrants further investigation, but is far from clinical application.", "abstract": "Colorectal cancer remains a therapeutic challenge due to systemic toxicity and the suboptimal efficacy of conventional therapies. Emerging evidence indicates that molecular hydrogen (H2) exerts antitumor effects through proliferation suppression and induction of a \"tumor dormancy\" phenotype characterized by cell cycle arrest and metabolic quiescence. Capitalizing on this mechanism, we engineered a platinum-incorporated metal-organic framework (PM) that integrates H2-mediated dormancy induction with 5-aminosalicylic acid (5-ASA)-potentiated NF-κB suppression. This system enables spatiotemporally light-controlled H2 generation vis-à-vis water splitting, which disrupts redox homeostasis while synchronously releasing 5-ASA to block NF-κB nuclear translocation, thereby collectively inducing sustained proliferative arrest and immunosuppressive tumor microenvironment remodeling. Tumor-localized PM decomposition generates photosensitizers that amplify therapeutic efficacy through catalytic ROS storms, representing a dual-modality strategy that couples H2-driven dormancy with ROS-mediated cytotoxicity. Mechanistic profiling reveals NF-κB suppression via modulation of the H2/5-ASA-mediated redox-inflammatory axis, systematically validated through multiomics analyses across three tumor models and clinical specimens. H2-induced dormancy sensitizes tumors to catalytic ROS attacks by potentiating metabolic vulnerabilities, while 5-ASA prevents dormancy from escaping through persistent NF-κB inactivation. This work introduces a nanomaterial-enabled approach to dormancy therapy, demonstrating the dual functionality of single-atom catalysts in precision catalytic H2 generation and immunomodulatory integration. It proposes a framework for intercepting tumor progression via coordinated cell cycle control and microenvironmental reprogramming.", "conclusion": "This work introduces a nanomaterial-enabled approach to dormancy therapy, demonstrating the dual functionality of single-atom catalysts in precision catalytic H2 generation and immunomodulatory integration. It proposes a framework for intercepting tumor progression via coordinated cell cycle control and microenvironmental reprogramming." }, { "pmid": "40885754", "year": 2025, "title": "Pyroptosis-responsive microspheres modulate the inflammatory microenvironment to retard osteoporosis in female mice.", "title_en": null, "title_de": "Pyroptose-responsive Mikrosphären modulieren die entzündliche Mikroumgebung zur Verzögerung der Osteoporose bei weiblichen Mäusen.", "journal": "Nature communications", "authors": "Lu et al.", "author_search": "lu lu", "doi": "10.1038/s41467-025-63456-5", "doi_url": "https://doi.org/10.1038/s41467-025-63456-5", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40885754/", "url": "https://h2medicine.org/studies/study-lu-2025-pyroptosis-responsive-microspheres-modulate/", "methods": [ "inhalation" ], "indications": [ "joints-rheumatology", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Lu — Pyroptosis-responsive microspheres modulate the inflammatory microenvironment to retard osteoporosis in female mice.", "summary": "Bone loss in osteoporosis is partly driven by a destructive inflammation mechanism called pyroptosis — and a newly designed implantable microsphere scaffold that releases hydrogen gas, magnesium ions, and an anti-inflammatory drug simultaneously can interrupt this process. In female mice, the scaffold reversed inflammatory bone microenvironments and significantly promoted bone tissue repair. This is a preclinical animal study; no human data are available. (Nature Communications, 2025.)", "assessment": "A methodologically interesting preclinical study that links pyroptosis to osteoporosis pathology and proposes H₂-containing composite implants as a local intervention. The multi-agent scaffold design is creative and the mechanistic rationale is well-supported. Decisive limitation: this is an animal study only — findings cannot be directly transferred to humans. Human osteoporosis is a systemic, multifactorial disease that a locally implanted scaffold cannot address in a generalised way. The DMF component (a known pharmaceutical) also raises questions about systemic exposure when implanted. Clinical translation requires substantial additional safety and efficacy work. Promising proof-of-concept for local bone-defect repair, not yet relevant for common osteoporosis management.", "abstract": "The treatment of osteoporosis and related bone defects remains challenging. This study identifies pyroptosis-driven inflammation as a key disruptor of bone homeostasis. To address this, we develop a magnesium-gelatin composite microsphere scaffold (GelMa/Mg/DMF MS) that exploit pyroptosis blockade and hydrogen-mediated inflammation regulation for osteoporosis treatment. This porous microsphere scaffold is implanted into bone defects to achieve the sustained release of hydrogen gas, magnesium ions (Mg2+), and dimethyl fumarate (DMF). DMF act by activating the nuclear factor erythroid-related factor 2 to prevent osteoblast pyroptosis, and combine with the antioxidant effects of hydrogen, effectively remodel the inflammatory microenvironment and create favorable conditions for the restoration of bone homeostasis. Mg2+ further expedite bone tissue repair. These results demonstrate that the GelMa/Mg/DMF MS effectively reverse inflammatory microenvironments both in vivo and in vitro, resulting in significant tissue repair. These results suggest the combination of hydrogen therapy and pyroptosis blockade as a potential therapeutic strategy.", "conclusion": "These results demonstrate that the GelMa/Mg/DMF MS effectively reverse inflammatory microenvironments both in vivo and in vitro, resulting in significant tissue repair. These results suggest the combination of hydrogen therapy and pyroptosis blockade as a potential therapeutic strategy." }, { "pmid": "40877145", "year": 2025, "title": "Immunomodulatory Effects of Molecular Hydrogen Therapy in Systemic Lupus Erythematosus With Pericarditis and Pleuritis: A Case Report.", "title_en": null, "title_de": "Immunmodulatorische Effekte der Therapie mit molekularem Wasserstoff bei systemischem Lupus erythematodes mit Perikarditis und Pleuritis: Ein Fallbericht", "journal": "In vivo (Athens, Greece)", "authors": "Tu et al.", "author_search": "tu tu", "doi": "10.21873/invivo.14103", "doi_url": "https://doi.org/10.21873/invivo.14103", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40877145/", "url": "https://h2medicine.org/studies/study-tu-2025-immunomodulatory-systemic-lupus-erythematosus/", "methods": [ "drinking-hrw" ], "indications": [ "cardiovascular", "immune-system", "oxidative-stress", "fundamentals-safety" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2025 · Tu et al. — Immunomodulatory Effects of Molecular Hydrogen Therapy in Systemic Lupus Erythematosus With Pericarditis and Pleuritis: A Case Report", "summary": "A 49-year-old woman with systemic lupus erythematosus complicated by pericarditis and pleuritis received hydrogen-rich water as an adjuvant in October 2024; serial immunophenotyping over the following weeks revealed a decreasing trend in Tr1 cells and an increasing trend in naïve regulatory T cells, transitional B cells, and Fas-expressing B cell subsets. (In Vivo, 2025.)", "assessment": "Single case report within a coherent series. Contributes a new immunological fingerprint (Tr1 ↓, naïve Treg ↑, transitional B ↑) that is distinct from but complementary to findings in companion reports. Limitations: n = 1, observational and uncontrolled, concurrent SLE therapies not fully detailed, no quantitative clinical outcomes (e.g., effusion resolution on imaging), short observation window from October 2024. The aggregation of multiple cases with overlapping immunological signals from this group is its main scientific value — no single case is conclusive.", "abstract": "BACKGROUND/AIM: Pericarditis is a common cardiovascular complication associated with systemic lupus erythematosus (SLE). Oxidative stress plays a significant role in disease pathology. Molecular hydrogen has emerged as a promising therapeutic option with its antioxidant, anti-inflammatory, and antiapoptotic properties. While prior studies have demonstrated its cardioprotective effects, research on its immunomodulatory potential in autoimmune diseases remains limited; therefore, this article presents a case study with SLE experiencing pericarditis and pleuritis, receiving hydrogen therapy in October 2024 as part of an effort to evaluate its potential in modulating immune responses and alleviating disease symptoms. CASE REPORT: This is the case of a 49-year-old Taiwanese female diagnosed with SLE, alongside pericarditis, pleuritis, and multi-organ impairments. Despite initial treatment and intermittent follow-ups, the patient experienced recurrent disease exacerbations, which was managed with immunomodulatory therapies. In October 2024, molecular hydrogen supplementation was introduced as an adjuvant therapy. Immunophenotypic analysis revealed dynamic changes in the percentages of immune cells, with decreasing trend of Tr1 cells and increasing trend of naïve Treg cells, B cell subsets expressing Fas, and transitional B cells following molecular hydrogen therapy. CONCLUSION: Molecular hydrogen therapy had potential to modulate immune markers in this case study. Further investigation into its clinical efficacy and safety is necessary for the development of treatment guidelines.", "conclusion": "Molecular hydrogen therapy had potential to modulate immune markers in this case study. Further investigation into its clinical efficacy and safety is necessary for the development of treatment guidelines." }, { "pmid": "40874435", "year": 2025, "title": "Hydrogen attenuates the senescence of adipose-derived stem cells and enhances their myogenic differentiation via modulation of the PRDX6/SIRT1/PGC-1α signaling pathway.", "title_en": null, "title_de": "Wasserstoff dämpft die Seneszenz von aus Fettgewebe gewonnenen Stammzellen und verstärkt deren myogene Differenzierung durch Modulation des PRDX6/SIRT1/PGC-1α-Signalwegs.", "journal": "Human & experimental toxicology", "authors": "Zhang et al.", "author_search": "zhang zhang", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40874435/", "url": "https://h2medicine.org/studies/study-zhang-2025-attenuates-senescence-adipose-derived/", "methods": [ "inhalation" ], "indications": [ "metabolic", "sports-exercise", "skin-aging", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Zhang — Hydrogen attenuates the senescence of adipose-derived stem cells and enhances their myogenic differentiation via modulation of the PRDX6/SIRT1/PGC-1α signaling pathway.", "summary": "Stem cells derived from fat tissue age over time, limiting their potential for regenerative therapies — and hydrogen gas treatment can slow this ageing while simultaneously improving the cells' ability to differentiate into muscle tissue. The study identifies the PRDX6/SIRT1/PGC-1α molecular pathway as a key mediator of hydrogen's protective effect. This is a cell-culture and animal study; no human data are available. (Human & Experimental Toxicology, 2025.)", "assessment": "A mechanistically well-executed cell/animal study on hydrogen's protective role against stem cell senescence. The pathway identification (PRDX6/SIRT1/PGC-1α) and the inhibition experiment provide genuine scientific value. Critical limitation: this is preclinical research — these are cell-culture and animal findings, not human evidence. The clinical potential for stem-cell-based regenerative therapies is real, but requires human studies to confirm whether H₂ pretreatment of ADSCs or systemic H₂ application improves patient outcomes. No human data exist. Results are promising as a mechanistic foundation, not as a treatment recommendation.", "abstract": "IntroductionAdipose-derived mesenchymal stem cells (ADSCs) are promising candidates for regenerative therapies, but their clinical application is limited by cellular aging. This study investigated the effects of hydrogen on ADSC senescence and myogenic differentiation, along with the underlying molecular mechanisms.MethodsADSCs were treated with hydrogen gas. Senescence was assessed using β-galactosidase staining, proliferation assays, measurements of mitochondrial oxidative stress, and protein expression analysis. Differentiation capacity was evaluated through MyHC immunofluorescence, MYOD expression profiling, and quantification of myogenic regulatory factors. Additionally, the key molecular pathway of hydrogen's action was investigated by pharmacologically inhibiting PRDX6.ResultsThe findings showed that hydrogen treatment reduced senescence and increased differentiation capacity, as evidenced by higher proportions of MyHC-positive cells, increased myogenin levels, and decreased Muscle RING finger protein1 (MuRF1) expression. Molecular investigations revealed activation of the PRDX6/SIRT1/PGC-1α axis, accompanied by elevated NQO-1 expression. Importantly, pharmacological inhibition of PRDX6 largely eliminated the protective effects of hydrogen on cellular aging, disrupted differentiation, and caused mitochondrial dysfunction.DiscussionThese results suggest that hydrogen can regulate ADSC behavior via PRDX6-driven activation of SIRT1/PGC-1α signaling, offering potential approaches to improve stem cell quality for regenerative medicine.", "conclusion": "Molecular investigations revealed activation of the PRDX6/SIRT1/PGC-1α axis, accompanied by elevated NQO-1 expression. Importantly, pharmacological inhibition of PRDX6 largely eliminated the protective effects of hydrogen on cellular aging, disrupted differentiation, and caused mitochondrial dysfunction.DiscussionThese results suggest that hydrogen can regulate ADSC behavior via PRDX6-driven activ" }, { "pmid": "40864154", "year": 2025, "title": "Local Delivery of Molecular Hydrogen by Fluorinated Zeolitic Imidazole Framework Nanosheets Boosts Cancer Immunotherapy.", "title_en": null, "title_de": "Lokale Verabreichung von molekularem Wasserstoff durch fluorierte zeolithische Imidazol-Gerüst-Nanoblätter verstärkt die Krebs-Immuntherapie.", "journal": "ACS applied materials & interfaces", "authors": "Liu et al.", "author_search": "liu liu", "doi": "10.1021/acsami.5c15739", "doi_url": "https://doi.org/10.1021/acsami.5c15739", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40864154/", "url": "https://h2medicine.org/studies/study-liu-2025-local-delivery-fluorinated-zeolitic/", "methods": [ "unspecified" ], "indications": [ "liver", "cancer", "immune-system" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Liu — Local Delivery of Molecular Hydrogen by Fluorinated Zeolitic Imidazole Framework Nanosheets Boosts Cancer Immunotherapy.", "summary": "A newly engineered nanomaterial can carry and locally release large amounts of molecular hydrogen (H₂) inside a tumour, while also amplifying the effect of immune checkpoint therapy. The fluorinated zeolitic imidazolate framework releases H₂ and zinc ions in the tumour microenvironment, killing cells and — surprisingly — increasing the expression of a surface signal that makes tumour cells better targets for anti-CD47 antibody therapy. In mouse melanoma models, tumour inhibition rates of 83–90 % were achieved — but this is entirely animal research. (ACS Applied Materials & Interfaces, 2025.)", "assessment": "An imaginative and mechanistically well-characterised preclinical study that identifies an unexpected synergy between local H₂ delivery and immune checkpoint therapy. The CD47-upregulation finding is novel and the triple-combination (H₂ + anti-CD47 + anti-PD-L1) data are impressive in the mouse model. However, this is entirely animal research — no human data exist, and results cannot be directly extrapolated to patients. The clinical gap is large: nanoparticle safety and tumour-specific delivery must be proven in humans, the CD47 upregulation effect may differ in human tumour biology, and melanoma mouse models are known to be poor predictors of human immunotherapy response. A compelling concept requiring substantial further development before any clinical relevance.", "abstract": "Identifying strategies to improve the efficacy of the immune checkpoint blockade (ICB) remains a major clinical need. Based on the high tissue penetration capability of hydrogen molecules (H2) and their immunomodulatory effects, this work proposes a local gas delivery strategy targeting the tumor microenvironment for high-efficacy hydrogen immunotherapy. We synthesized hepta-fluorinated zeolitic imidazolate frameworks nanosheet (F7-ZIF) with high H2 payload, sustained acid-responsive gas release property, and biodegradation. H2-loaded F7-ZIF (F7-ZIF/H2) effectively released H2 and Zn2+ to induce significant mitochondrial damage and cell apoptosis. More importantly, F7-ZIF/H2 considerably upregulated the expression of CD47 (\"do not eat me\" signal) on tumor cells, which increases target accessibility for anti-CD47 antibody, thereby enhancing their binding efficiency. RNA-seq suggests that the CD47 antibody not only blocks the \"do not eat me\" signal (mediated by CD47-SIRPα interactions) but also engages Fc receptors on macrophages through its Fc region to trigger antibody-dependent cellular phagocytosis. In melanoma tumor models with small (∼50 mm3) and large sized established tumors (∼200 mm3), the combination of F7-ZIF/H2 and anti-CD47 reaches 90% and 83% of tumor inhibition rate, respectively, compared to free anti-CD47. When further combined with anti-PD-L1, the therapeutic system triggers systemic T cell immunity that rejects the progression of both primary and distal tumors. This work provides insights into gas-assisted cancer immunotherapy.", "conclusion": "When further combined with anti-PD-L1, the therapeutic system triggers systemic T cell immunity that rejects the progression of both primary and distal tumors. This work provides insights into gas-assisted cancer immunotherapy." }, { "pmid": "40850177", "year": 2025, "title": "Integrating QSAR modeling, ADMET screening, molecular docking, and molecular dynamics simulations to identify potential MCF-7 inhibitors.", "title_en": null, "title_de": "Integration von QSAR-Modellierung, ADMET-Screening, molekularem Docking und Molekulardynamik-Simulationen zur Identifizierung potenzieller MCF-7-Inhibitoren.", "journal": "Computers in biology and medicine", "authors": "Valizadeh et al.", "author_search": "valizadeh valizadeh", "doi": "10.1016/j.compbiomed.2025.110972", "doi_url": "https://doi.org/10.1016/j.compbiomed.2025.110972", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40850177/", "url": "https://h2medicine.org/studies/study-valizadeh-2025-integrating-qsar-modeling-admet/", "methods": [ "unspecified" ], "indications": [ "cancer" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Valizadeh — Integrating QSAR modeling, ADMET screening, molecular docking, and molecular dynamics simulations to identify potential MCF-7 inhibitors.", "summary": "This computational study used mathematical models to predict which of 2,435 naphthoquinone chemical compounds might inhibit breast cancer cells — and used hydrogen-suppressed molecular graphs as part of the mathematical descriptor framework. Sixteen promising candidates were selected for virtual docking simulations against a cancer target protein, with one compound showing particularly strong binding. This is a purely in-silico (computer-based) study; no biological experiments with hydrogen gas or hydrogen-rich water were performed. (Computers in Biology and Medicine, 2025.)", "assessment": "This study has no direct relevance to hydrogen gas therapy or hydrogen-rich water. The word „hydrogen“ in the title refers to a mathematical graph-theory concept used in cheminformatics. The study is a standard computational drug-discovery workflow for breast cancer, identifying potential naphthoquinone-based inhibitors via QSAR modelling and docking — with no experimental validation yet. Completely in-silico: no cells, no animals, no humans. The identified compound A14 is a theoretical candidate requiring laboratory confirmation before any biological claims can be made. Included here for completeness; its relevance to H₂ medicine is negligible.", "abstract": "In this study, quantitative structure-activity relationship (QSAR) models were developed by the Monte Carlo technique to predict the anti-breast cancer activity of 144 novel 1,2-naphthoquinone and 1,4-naphthoquinone derivatives against MCF-7 breast cancer cells. To establish QSAR models, a balance of correlation techniques involving the index of ideality of correlation (IIC) and the correlation intensity index (CII), as well as an optimal hybrid descriptor derived from the integration of the Simplified Molecular Input Line Entry System (SMILES) and molecular hydrogen-suppressed graphs (HSG), was used. The resulting models provided valuable information about identifying molecular fragments that enhance or reduce biological activity. The pIC50 values of 2435 naphthoquinone derivatives, including newly synthesized compounds, were predicted using the best QSAR model. Among them, 67 compounds showed pIC50 values greater than 6. After applying the absorption, distribution, metabolism, excretion, and toxicity (ADMET) filter, 16 promising compounds were selected for docking studies. The candidate inhibitors were docked at the binding site of topoisomerase IIα (PDB ID: 1ZXM) to assess their binding affinity. Compound A14, which exhibited the highest binding affinity, underwent molecular dynamics simulations for 300 ns, demonstrating stable interactions with the target protein. Doxorubicin served as a reference control to validate the efficacy of compound A14. These findings offer valuable insights for designing potent inhibitors against breast cancer.", "conclusion": "Doxorubicin served as a reference control to validate the efficacy of compound A14. These findings offer valuable insights for designing potent inhibitors against breast cancer." }, { "pmid": "40845957", "year": 2025, "title": "Hydrogen promoted mitochondrial autophagy and alleviated CIH-induced vascular endothelial cell senescence by regulating oxidative stress.", "title_en": null, "title_de": "Wasserstoff förderte die mitochondriale Autophagie und linderte die CIH-induzierte Seneszenz vaskulärer Endothelzellen durch Regulierung von oxidativem Stress.", "journal": "European journal of pharmacology", "authors": "Li et al.", "author_search": "li li", "doi": "10.1016/j.ejphar.2025.178078", "doi_url": "https://doi.org/10.1016/j.ejphar.2025.178078", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40845957/", "url": "https://h2medicine.org/studies/study-li-2025-promoted-mitochondrial-autophagy-alleviated/", "methods": [ "unspecified" ], "indications": [ "neurology", "cardiovascular", "respiratory", "skin-aging", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Li — Hydrogen promoted mitochondrial autophagy and alleviated CIH-induced vascular endothelial cell senescence by regulating oxidative stress.", "summary": "Obstructive sleep apnoea (OSA) causes repeated oxygen deficits that accelerate ageing of the blood vessel lining — and molecular hydrogen (H₂) can protect vascular endothelial cells against this premature ageing by activating cellular clean-up processes (autophagy) and reducing oxidative stress. In mice with experimentally induced chronic intermittent hypoxia, H₂ treatment improved aortic function and reduced senescence markers. This is an animal and cell study — no human data are available. (European Journal of Pharmacology, 2025.)", "assessment": "A solid mechanistic animal study demonstrating that H₂ protects vascular endothelial cells from OSA-induced senescence via Nrf2-mediated mitophagy. The functional vascular readouts (echocardiography, aortic ring vasodilation) strengthen the findings beyond molecular markers alone. The Nrf2-silencing experiment provides causal depth. Decisive limitation: entirely animal and cell research — no human evidence exists. The translation from a murine CIH model to human OSA with vascular complications requires clinical trials. The paper correctly notes this as „providing evidence for clinical application“ — which is aspirational, not demonstrative. A meaningful mechanistic contribution, not a therapeutic proof.", "abstract": "Obstructive sleep apnea (OSA), characterized by recurrent upper airway collapse during sleep, has been linked to systemic physiological impairment and accelerated vascular senescence through chronic intermittent hypoxia (CIH). Currently, there is no approved medication to treat the complications of OSA. Molecular hydrogen (H2), an anti-oxidative therapeutic agent, plays an important role in regulating cardiovascular and anti-aging. In this study, we aimed to investigate the therapeutic effect of H2 on OSA-associated vascular endothelial aging by establishing a mouse model induced by CIH and explore the mechanism of H2 from the perspective of oxidative stress and autophagy. Echocardiography and aortic ring vasodilatory response were employed to assess the impact of H2 on the aortic function in CIH mice. Haematoxylin and eosin staining, transmission electron microscopy, SA-β-gal staining, DHE staining, and immunofluorescence staining were utilized to observe the changes in histopathology and protein expression. The results demonstrated that H2 alleviated CIH-induced vascular endothelial aging by improving the pathological injury of the aorta, alleviating vasodilation dysfunction, decreasing the expression of oxidative stress and aging markers, and increasing the expression of autophagy-related proteins. Mechanism investigations revealed that H2 could inhibit oxidative stress and activate autophagy pathways, but silencing Nuclear factor-erythroid 2 related factor 2 (Nrf2) impaired the ability of H2 to ameliorate endothelial senescence in the CIH cell model. These suggest that H2 can activate mitochondrial autophagy, reduce oxidative stress, and improve the senescence of endothelial cells induced by CIH, providing evidence for the clinical application of H2 in OSA-related vascular endothelial senescence diseases.", "conclusion": "Mechanism investigations revealed that H2 could inhibit oxidative stress and activate autophagy pathways, but silencing Nuclear factor-erythroid 2 related factor 2 (Nrf2) impaired the ability of H2 to ameliorate endothelial senescence in the CIH cell model. These suggest that H2 can activate mitochondrial autophagy, reduce oxidative stress, and improve the senescence of endothelial cells induced b" }, { "pmid": "40833316", "year": 2025, "title": "Nano-Bubble Hydrogen Water in Wet-Wrap Dressing Improves the Severity of Pediatric Patients With Atopic Dermatitis.", "title_en": null, "title_de": "Nanobläschen-Wasserstoffwasser im Wet-Wrap-Verband verbessert den Schweregrad bei pädiatrischen Patienten mit atopischer Dermatitis", "journal": "Journal of pediatric health care : official publication of National Association of Pediatric Nurse Associates & Practitioners", "authors": "Wong et al.", "author_search": "wong wong", "doi": "10.1016/j.pedhc.2025.07.005", "doi_url": "https://doi.org/10.1016/j.pedhc.2025.07.005", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40833316/", "url": "https://h2medicine.org/studies/study-wong-2025-nano-bubble-wet-wrap/", "methods": [ "drinking-hrw" ], "indications": [ "skin-aging", "immune-system", "allergy", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2025 · Wong et al. — Nano-Bubble Hydrogen Water in Wet-Wrap Dressing Improves the Severity of Pediatric Patients With Atopic Dermatitis", "summary": "In 20 children with atopic dermatitis, wet-wrap dressings soaked in nano-bubble hydrogen water significantly reduced erythema, dryness, and total skin severity scores compared to baseline; in a split-body sub-study (8 patients), hydrogen-water-treated limbs improved significantly more than limbs treated with plain water. (Journal of Pediatric Health Care, 2025.)", "assessment": "A small but methodologically thoughtful study with a built-in split-body control design in a subset of patients. The statistically significant improvements in erythema and dryness in a paediatric population, with no reported adverse effects, are clinically encouraging. Limitations: n = 20 (split-body n = 8), no blinding, no long-term follow-up, no patient-reported itch or quality-of-life outcomes, concurrent topical therapy not described. The safety profile and non-invasive application route make this a low-risk candidate for a larger randomised controlled trial in paediatric atopic dermatitis.", "abstract": "INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin condition in which reactive oxygen species (ROS) contribute to its pathogenesis. Hydrogen water (HW), with potent antioxidant properties, may counteract ROS and improve AD symptoms. This study assessed the clinical efficacy of nano-HW wet-wrap dressing in AD. METHOD: Twenty AD patients received wet-wrap therapy using sterile gauze soaked in nano-bubble HW. In eight patients, a split-body design was used: one limb with nano-HW, the other with pure water. RESULTS: HW wet-wrap significantly reduced erythema (0.5 ± 0.69, p = .01), dryness (0.7 ± 0.57, p = .002), and total score (1.55 ± 1.64, p < .0001), while pure water showed no significant changes. HW-treated limbs improved more than pure water-treated limbs. DISCUSSION: HW wet-wrap therapy is a safe, effective adjunct for pediatric AD, improving erythema, dryness, and hydration while limiting systemic side effects.", "conclusion": "HW-treated limbs improved more than pure water-treated limbs. DISCUSSION: HW wet-wrap therapy is a safe, effective adjunct for pediatric AD, improving erythema, dryness, and hydration while limiting systemic side effects." }, { "pmid": "40733848", "year": 2025, "title": "3D printing combined with pH-induced 4D printed iron(III)-oxidized starch gels for controlled iron delivery and enhanced iron supplementation.", "title_en": null, "title_de": "3D-Druck kombiniert mit pH-induzierten 4D-gedruckten Gelen aus Eisen(III)-oxidierter Stärke zur kontrollierten Eisenabgabe und verbesserten Eisensupplementierung.", "journal": "Carbohydrate polymers", "authors": "Qiu et al.", "author_search": "qiu qiu", "doi": "10.1016/j.carbpol.2025.123933", "doi_url": "https://doi.org/10.1016/j.carbpol.2025.123933", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40733848/", "url": "https://h2medicine.org/studies/study-qiu-2025-printing-combined-induced-printed/", "methods": [ "drinking-hrw" ], "indications": [ "liver", "sports-exercise", "oxidative-stress", "fundamentals-safety" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Qiu — 3D printing combined with pH-induced 4D printed iron(III)-oxidized starch gels for controlled iron delivery and enhanced iron supplementation.", "summary": "Iron deficiency anaemia can be treated more effectively with a new type of 3D-/4D-printed starch gel that releases iron only in the small intestine, not in the stomach — improving bioavailability while reducing side effects. The study uses oxidised starch cross-linked with iron ions; hydrogen plays a structural role in the starch network, not a therapeutic one. This is an in-vitro and animal study; the connection to hydrogen gas therapy is indirect and structural. (Carbohydrate Polymers, 2025.)", "assessment": "This study has limited direct relevance to molecular hydrogen (H₂) therapy. The term „hydrogen“ in the paper describes chemical hydrogen bonding in starch networks — a standard structural chemistry concept — not therapeutic hydrogen gas or hydrogen-rich water. The study itself is a materials-science contribution to iron supplementation technology, with solid in-vitro and animal data showing improved iron bioavailability. As a preclinical study, results are not directly transferable to human patients. The 4D-printing concept for targeted mineral delivery is innovative and warrants further clinical evaluation — but as an iron supplement technology, not as H₂ therapy.", "abstract": "Iron deficiency anemia (IDA) necessitates effective iron supplementation with high bioavailability and controlled release. This study developed 4D-printed ferric-oxidized starch gels (4D-FeOMS) as a stimulus-responsive platform for targeted iron delivery. By combining hot-extrusion 3D printing with pH-triggered 4D transformation, Fe3+ was effectively coordinated within oxidized starch networks via ionic crosslinking. Rheological analysis revealed Fe3+ hydrolysis disrupted starch molecular hydrogen bonding and reducing molecular weight, leading to diminished gel network uniformity and density. Compared to 3D-printed samples (3D-FeOMS), 4D-FeOMS exhibited red-shifted CO FTIR peaks, lower Fe 2p XPS binding energies, and reduced correlation length (ξ), indicating improved molecular entanglement and network uniformity. In vitro digestion demonstrated gastric resistance (<30 % Fe3+ release) and rapid iron release (>85 %) in the proximal small intestine. In vivo evaluation in IDA mice showed that 4D-FeOMS significantly restored biochemical and hematological parameters, increased organ iron stores (restored >94.6 %), and enhanced antioxidant enzyme activity, outperforming iron salts and 3D-FeOMS. Mechanistically, 4D-FeOMS optimized hepcidin expression and regulated ferritin/transferrin levels, facilitating systemic iron transport. Notably, 4D-FeOMS-10 % demonstrated iron supplementation efficacy performance due to the appropriate iron addition and optimal Fe3+ complexation. These findings highlighted the potential of 4D-printed starch-based platforms as intelligent mineral delivery systems for treating micronutrient deficiencies.", "conclusion": "Notably, 4D-FeOMS-10 % demonstrated iron supplementation efficacy performance due to the appropriate iron addition and optimal Fe3+ complexation. These findings highlighted the potential of 4D-printed starch-based platforms as intelligent mineral delivery systems for treating micronutrient deficiencies." }, { "pmid": "40694834", "year": 2025, "title": "Hydrogen-Rich Water Consumption for Acute and Residual Fatigue After Simulated Football Matches: Protocol for a Randomized, Double-Blinded, Placebo-Controlled, Parallel Trial.", "title_en": null, "title_de": "Konsum von wasserstoffreichem Wasser gegen akute und residuale Ermüdung nach simulierten Fußballspielen: Protokoll für eine randomisierte, doppelblinde, placebokontrollierte Parallelstudie", "journal": "JMIR research protocols", "authors": "Hruby et al.", "author_search": "hruby hruby", "doi": "10.2196/69744", "doi_url": "https://doi.org/10.2196/69744", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40694834/", "url": "https://h2medicine.org/studies/study-hruby-2025-consumption-acute-residual-fatigue/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise", "neurology", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2025 · Hruby et al. — Hydrogen-Rich Water Consumption for Acute and Residual Fatigue After Simulated Football Matches: Protocol for a Randomized, Double-Blinded, Placebo-Controlled, Parallel Trial", "summary": "This publication describes the protocol for a rigorous randomised, double-blinded, placebo-controlled trial investigating whether hydrogen-rich water consumed before a simulated elite football match reduces acute and residual fatigue over a 72-hour recovery period — assessed via neuromuscular performance tests, biochemical markers, and perceptual measures. No results are available yet; data collection was scheduled for August 2025. (JMIR Research Protocols, 2025.)", "assessment": "This is a protocol publication only — no results yet. Its value is the transparent pre-registration of a high-quality sports trial. The design (double-blind, placebo-controlled, parallel, elite athletes) is among the strongest proposed in the H₂ sports literature. What to watch: adherence to blind in a sports context (taste/smell of HRW vs. placebo); ecological validity of a simulated match; the planned sample size is not specified in the abstract (a key omission for power assessment); results expected in late 2025 or early 2026. If the trial delivers, it will provide some of the cleanest data on H₂ and exercise recovery to date.", "abstract": "BACKGROUND: Football matches induce acute and residual fatigue, impairing neuromuscular, metabolic, and perceptual performance. Hydrogen-rich water (HRW) is a novel intervention with antifatigue and antioxidative properties. The intermittent high-intensity nature of football, which includes frequent accelerations, decelerations, sprints, changes of direction, and physical contacts, imposes substantial demands on both central and peripheral physiological systems. This results in acute fatigue, observable during or immediately after a match, and residual fatigue, which can persist for 24-72 hours post match, depending on the intensity, match context, and recovery strategies. OBJECTIVE: This study will investigate the effects of pre-exercise HRW administration versus a placebo on neuromuscular performance, biochemical markers, and perceptual measures of fatigue during a 72-hour recovery after a simulated football match. METHODS: Using a randomized, double-blinded, placebo-controlled, parallel design, elite junior football players will undergo neuromuscular performance assessments (repeated sprint ability and countermovement jump test). Metabolic fatigue will be measured by creatine kinase level and muscle soreness, rated using a visual analog scale. These assessments will occur at critical time points: immediately post warm-up; directly following the simulated football match to detect acute fatigue; and 24, 48, and 72 hours after training sessions to detect residual fatigue. RESULTS: Data collection has been scheduled with the clubs to coincide with the beginning of the players' transition period (ie, at the start of August 2025). The expected duration of data collection, including the initial medical examination, is planned to be 1 month. We anticipate publishing the results in late 2025 or during the first half of 2026. CONCLUSIONS: This study will assess the influence of molecular hydrogen on acute fatigue manifestation and recovery quality during a 72-hour period after a simulated football match. The potential positive effects of molecular hydrogen, such as attenuation of oxidative stress, reduction in muscle damage markers, and accelerated neuromuscular recovery, may contribute to faster restoration of functional capacities. If confirmed, these effects could enhance players' readiness to return to high-intensity training and optimize the structure of microcycles in competitive periods. Additionally, understanding the recovery dynamics facilitated by HRW may inform evidence-based recovery strategies and support individualized player monitoring frameworks. The possible positive effect of molecular hydrogen would speed up the players' readiness to train after the match and help protect players against illness and noncontact injuries.", "conclusion": "This study will assess the influence of molecular hydrogen on acute fatigue manifestation and recovery quality during a 72-hour period after a simulated football match. The potential positive effects of molecular hydrogen, such as attenuation of oxidative stress, reduction in muscle damage markers, and accelerated neuromuscular recovery, may contribute to faster restoration of functional capacities. If confirmed, these effects could enhance players' readiness to return to high-intensity training" }, { "pmid": "40621736", "year": 2025, "title": "Magnesium hydride-induced hydrogen therapy for enhanced sonodynamic therapy.", "title_en": null, "title_de": "Magnesiumhydrid-induzierte Wasserstofftherapie zur verstärkten sonodynamischen Therapie.", "journal": "Materials horizons", "authors": "Huang et al.", "author_search": "huang huang", "doi": "10.1039/d5mh00585j", "doi_url": "https://doi.org/10.1039/d5mh00585j", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40621736/", "url": "https://h2medicine.org/studies/study-huang-2025-magnesium-hydride-induced-enhanced/", "methods": [ "unspecified" ], "indications": [ "cancer", "immune-system" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Huang — Magnesium hydride-induced hydrogen therapy for enhanced sonodynamic therapy.", "summary": "Combining molecular hydrogen (H₂) released from magnesium hydride with ultrasound-activated cancer therapy (sonodynamic therapy, SDT) significantly improves anti-tumour efficacy and enhances the response to immune checkpoint inhibitors in mice. The H₂ amplifies tumour cell destruction and — through its alkaline by-products — neutralises the acidic tumour environment that normally suppresses immune responses. This is an animal study; no human data are available. (Materials Horizons, 2025.)", "assessment": "A mechanistically rich preclinical study combining three modalities (H₂, SDT, anti-PD-1) with sound scientific rationale and promising murine efficacy data. The mechanistic logic — H₂ amplifies SDT, MgH₂ by-products reverse TME acidity, PD-1 upregulation enhances checkpoint therapy — is internally consistent. Critical limitation: this is an animal study only — results cannot be directly extrapolated to humans. SDT itself is not yet standard clinical practice, and adding two further agents (H₂ and anti-PD-1) multiplies the translational complexity. The paper claims broad potential as a „generalizable approach“ — appropriate as a research direction but not as a clinical claim. No human data exist.", "abstract": "The tumor microenvironment (TME) is typically immunosuppressive, playing a crucial role in tumor progression, immune evasion, and therapeutic resistance, all of which significantly impede the efficacy of cancer therapies1. Herein, we propose that magnesium hydride (MgH2)-induced hydrogen (H2) therapy can synergistically enhance barium titanate (BTO)-mediated sonodynamic therapy (SDT) while modulating the TME to improve the efficacy of immune checkpoint inhibitors (aPD-1). Specifically, ultrasound (US) activated BTO to trigger SDT and induce immunogenic cell death (ICD), while the sustained release of H2 from MgH2 microspheres amplifies tumor cell destruction, thereby promoting immune cell recruitment to the tumor site. Meanwhile, the hydroxide ions (OH-) and magnesium ions (Mg2+) generated by MgH2 alleviate the acidic TME, reversing immune suppression and enhancing T-cell-mediated antitumor responses. In the CT26 tumor model, the synergistic combination of SDT and MgH2 therapy significantly enhances the anti-tumor efficacy of SDT compared to that of BTO alone, leading to prolonged survival of treated mice. Moreover, MgH2 upregulates PD-1 expression in T cells, markedly improving the sensitivity of tumors to aPD-1 therapy. This strategy provides a generalizable approach for enhancing SDT, demonstrating its broad potential in anti-tumor treatment and presenting a promising avenue for overcoming resistance to immune checkpoint inhibitors.", "conclusion": "Moreover, MgH2 upregulates PD-1 expression in T cells, markedly improving the sensitivity of tumors to aPD-1 therapy. This strategy provides a generalizable approach for enhancing SDT, demonstrating its broad potential in anti-tumor treatment and presenting a promising avenue for overcoming resistance to immune checkpoint inhibitors." }, { "pmid": "40590161", "year": 2025, "title": "Predicting Therapeutic Response to Molecular Hydrogen in Autoimmune Diseases via Immunophenotyping.", "title_en": null, "title_de": "Vorhersage des therapeutischen Ansprechens auf molekularen Wasserstoff bei Autoimmunerkrankungen mittels Immunphänotypisierung", "journal": "APMIS : acta pathologica, microbiologica, et immunologica Scandinavica", "authors": "Lui et al.", "author_search": "lui lui", "doi": "10.1111/apm.70040", "doi_url": "https://doi.org/10.1111/apm.70040", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40590161/", "url": "https://h2medicine.org/studies/study-lui-2025-predicting-therapeutic-response-autoimmune/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise", "respiratory", "joints-rheumatology", "immune-system", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2025 · Lui et al. — Predicting Therapeutic Response to Molecular Hydrogen in Autoimmune Diseases via Immunophenotyping", "summary": "Can we predict in advance which autoimmune patients will benefit from H₂ therapy? This prospective study in 25 patients (rheumatoid arthritis, lupus, and others) developed a novel prediction index — the HRPI — based on immune cell profiles. An HRPI below −0.3 reliably predicted favorable clinical response (ROC = 0.94). The study also showed that H₂ significantly shifted 15 out of 108 immune cell subsets. (APMIS, 2025.)", "assessment": "This study is one of the more ambitious H₂ clinical papers to date in autoimmunology, introducing a biomarker-based prediction framework. The HRPI's ROC of 0.94 is striking, but must be interpreted cautiously: the sample is very small (n = 25, with subgroups as small as n = 4–7), there is no placebo control group, and the H₂ delivery used coral calcium capsules — a compound that may introduce confounders (calcium, mineral content). Fatigue as an outcome measure, while patient-relevant, is subjective. Flow cytometry was used rigorously with 108 subsets, which is a methodological strength. The HRPI requires independent validation in larger cohorts before clinical adoption. Overall: a genuinely interesting step forward, but preliminary.", "abstract": "Autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), are characterized by immune dysregulation that leads to chronic inflammation and organ damage. Current therapeutic strategies-including corticosteroids, immunosuppressants, and biologics-often exhibit variable efficacy and are associated with potential adverse effects. Molecular hydrogen, recognized for its ability to scavenge mitochondrial reactive oxygen species and inhibit the NLRP3 inflammasome, has emerged as a promising adjunctive treatment. However, its immunomodulatory effects remain insufficiently defined. This study aimed to evaluate the immunological effects of molecular hydrogen-assisted therapy (MHAT) on immune cell subsets and to identify potential predictive biomarkers of treatment efficacy. A total of 25 patients with autoimmune diseases who received MHAT were included (RA: n = 14; SLE: n = 7; others: n = 4, including one each with psoriatic arthritis, primary Sjögren's syndrome, immune-related interstitial lung disease, and diffuse idiopathic skeletal hyperostosis). An additional 15 untreated RA patients served as controls for the assessment of MHAT-induced changes in lymphocyte profiles and type 1 regulatory T (Tr1) cells. MHAT was administered orally at a daily dose of 170 mg hydrogen-enriched coral calcium for three months. Immune phenotyping of T cells, B cells, and regulatory T cells was performed using flow cytometry before and after treatment. Among the 108 immune subsets analyzed, 15 exhibited significant changes, including 11 T cell and 4 B cell subsets. Disease-specific immune modulation was observed in RA patients, particularly characterized by increased proportions of programmed cell death protein 1 (PD-1+) T cells and Fas+ B cells, and a marked reduction in Tr1 cells compared to patients with SLE or other autoimmune diseases. Based on baseline immune profiles and the percent change in fatigue scores (assessed by the Brief Fatigue Inventory, BFI-T), a Hydrogen-assisted Treatment Response Prediction Index (HRPI) was developed, demonstrating strong predictive performance (ROC = 0.9375, p = 0.0118). HRPI values below -0.3 predicted favorable clinical responses, whereas values near zero were associated with poor outcomes. HRPI shows potential as a predictive biomarker for MHAT efficacy and guides personalized autoimmune treatment.", "conclusion": "HRPI values below -0.3 predicted favorable clinical responses, whereas values near zero were associated with poor outcomes. HRPI shows potential as a predictive biomarker for MHAT efficacy and guides personalized autoimmune treatment." }, { "pmid": "40579028", "year": 2025, "title": "Molecular Hydrogen Therapy in Rheumatoid Arthritis: A Case Report on the Amelioration of Methotrexate-induced Myelosuppression and Immune Modulation.", "title_en": null, "title_de": "Therapie mit molekularem Wasserstoff bei rheumatoider Arthritis: Ein Fallbericht über die Besserung der Methotrexat-induzierten Myelosuppression und Immunmodulation", "journal": "In vivo (Athens, Greece)", "authors": "Tu et al.", "author_search": "tu tu", "doi": "10.21873/invivo.14014", "doi_url": "https://doi.org/10.21873/invivo.14014", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40579028/", "url": "https://h2medicine.org/studies/study-tu-2025-rheumatoid-arthritis-amelioration-methotrexate/", "methods": [ "drinking-hrw" ], "indications": [ "liver", "neurology", "kidney-dialysis", "joints-rheumatology", "immune-system", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2025 · Tu et al. — Molecular Hydrogen Therapy in Rheumatoid Arthritis: A Case Report on the Amelioration of Methotrexate-induced Myelosuppression and Immune Modulation", "summary": "Methotrexate (MTX) is essential for rheumatoid arthritis but can cause dangerous bone marrow suppression. This case report documents a 66-year-old woman with severe MTX-induced pancytopenia, liver failure, and acute kidney injury who showed marked clinical improvement after molecular hydrogen therapy was introduced. Flow cytometry revealed progressive increases in regulatory T cell populations with no adverse events. (In Vivo, 2025.)", "assessment": "This is a single case report — the weakest level of clinical evidence. No control, no way to attribute recovery exclusively to H₂ (MTX was also discontinued, which alone would trigger recovery). The patient's spontaneous improvement from MTX removal cannot be separated from any H₂ effect. The immune phenotyping adds mechanistic texture but cannot establish causality at n=1. Honestly: H₂ may have contributed, but we cannot know. The value lies in the detailed immune profiling accompanying a dramatic clinical scenario. This warrants prospective study of H₂ as an adjunct in MTX-treated RA patients to assess cytoprotective or immunomodulatory synergy.", "abstract": "BACKGROUND/AIM: Rheumatoid arthritis (RA) is a chronic autoimmune disease with systemic manifestations. Methotrexate (MTX) remains a cornerstone of RA treatment, offering significant therapeutic benefits; however, it is also associated with adverse effects, particularly myelosuppression. Molecular hydrogen, recognized for its anti-inflammatory and antioxidant properties, has demonstrated potential in mitigating oxidative stress and modulating immune responses in RA. This study aimed to evaluate the efficacy of molecular hydrogen therapy in alleviating MTX-induced myelosuppression while preserving its immunoregulatory effects in a patient with RA. CASE REPORT: We present the case of a 66-year-old Taiwanese female diagnosed with RA according to the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria. The patient presented to the emergency department on August 30, 2024, with oral ulcers, sore throat, weakness, and diarrhea. Clinical assessment revealed hypotension, tachycardia, pancytopenia, hepatic insufficiency, and acute kidney injury. Outpatient medications were discontinued, and molecular hydrogen therapy was initiated. The patient exhibited marked clinical improvement, with normalization of laboratory parameters. Flow cytometry analysis demonstrated a progressive increase in the percentages of PD-1+ subsets of Th and Tc cells, as well as memory and activated regulatory T (Treg) cells. In contrast, B regulatory (Breg) cell levels remained unchanged. No adverse events were observed during the course of hydrogen therapy. CONCLUSION: This is the first case report to highlight severe MTX-induced myelosuppression in an RA patient and to demonstrate the potential of molecular hydrogen therapy in modulating immune markers.", "conclusion": "This is the first case report to highlight severe MTX-induced myelosuppression in an RA patient and to demonstrate the potential of molecular hydrogen therapy in modulating immune markers." }, { "pmid": "40579023", "year": 2025, "title": "Molecular Hydrogen as an Adjuvant Therapy in Comorbid Sjögren's Syndrome, SLE, and ILD: A Case Report on Immune Modulation and Fatigue Reduction.", "title_en": null, "title_de": "Molekularer Wasserstoff als adjuvante Therapie bei komorbidem Sjögren-Syndrom, SLE und ILD: Ein Fallbericht über Immunmodulation und Reduktion der Ermüdung", "journal": "In vivo (Athens, Greece)", "authors": "Tsai et al.", "author_search": "tsai tsai", "doi": "10.21873/invivo.14018", "doi_url": "https://doi.org/10.21873/invivo.14018", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40579023/", "url": "https://h2medicine.org/studies/study-tsai-2025-adjuvant-comorbid-sjoegren-syndrome/", "methods": [ "unspecified" ], "indications": [ "liver", "sports-exercise", "respiratory", "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2025 · Tsai et al. — Molecular Hydrogen as an Adjuvant Therapy in Comorbid Sjögren's Syndrome, SLE, and ILD: A Case Report on Immune Modulation and Fatigue Reduction", "summary": "A 69-year-old woman with overlapping Sjögren's syndrome, systemic lupus erythematosus (SLE), and interstitial lung disease (ILD) — a difficult-to-treat triad — showed notable clinical improvements after adding molecular hydrogen therapy to her regimen. Symptoms including dry mouth, insomnia, breathlessness, and chest pain resolved over several months. Corticosteroids were tapered, and nighttime oxygen dependency was reduced. (In Vivo, 2025.)", "assessment": "A single case report with multiple confounders: concurrent high-dose vitamin C, ongoing corticosteroid therapy being tapered (itself a dynamic confounder), and no control or washout period. The multi-system improvement is clinically interesting but cannot be attributed to H₂ alone. Pulmonary imaging improvement in ILD is a meaningful endpoint, but details about imaging methodology and comparison criteria are limited. The honest take: this case is useful as a safety signal and hypothesis generator, but it proves nothing about H₂ efficacy in isolation. The combination with vitamin C and corticosteroid taper must be disentangled in future controlled work.", "abstract": "BACKGROUND/AIM: Systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) are chronic autoimmune diseases that often coexist. They share features such as systemic inflammation and multi-organ involvement and typically require long-term immunosuppressive treatment. However, long-term use of immunosuppressants can cause serious side effects, highlighting the need for adjunct therapies. Molecular hydrogen (H2) therapy shows anti-inflammatory, antioxidant, and immunomodulatory properties, with potential benefits in liver, lung, and metabolic diseases. This case report examines a patient with overlapping SLE, SS, and interstitial lung disease (ILD), evaluating the effects of molecular hydrogen therapy on fatigue, immune modulation, and cardiac function. CASE REPORT: We present the case of a 69-year-old female diagnosed with Sjögren's syndrome, SLE, and ILD. The patient exhibited chronic symptoms, including xerostomia, xerophthalmia, and respiratory distress, for which she had been receiving corticosteroids and immunomodulatory therapy. Given the persistent disease burden and concerns regarding long-term immunosuppressive therapy, molecular hydrogen therapy was introduced as an adjunctive treatment. Over several months, the patient experienced notable clinical improvements, including resolution of xerostomia, insomnia, dyspnea, chest pain, and dizziness. These symptomatic improvements correlated with favorable immunological shifts in T and B cell subsets, enhanced pulmonary imaging findings, and a reduction in inflammatory markers. Additionally, the patient reported a significant decrease in fatigue, allowing corticosteroid tapering and less reliance on nighttime oxygen. Ongoing hydrogen therapy with high-dose vitamin C maintained disease stability and improved quality of life. CONCLUSION: This case highlights the potential of molecular hydrogen (H2) therapy as a safe, effective adjunct in managing overlapping Sjögren's syndrome, SLE, and ILD. H2 therapy improved immune profiles and stabilized symptoms in a patient unresponsive to standard treatments.", "conclusion": "This case highlights the potential of molecular hydrogen (H2) therapy as a safe, effective adjunct in managing overlapping Sjögren's syndrome, SLE, and ILD. H2 therapy improved immune profiles and stabilized symptoms in a patient unresponsive to standard treatments." }, { "pmid": "40295001", "year": 2025, "title": "Molecular Hydrogen Capsule Therapy for Primary Biliary Cholangitis With Elevated IgG4: A Case Report on Immune Marker Normalization.", "title_en": null, "title_de": "Therapie mit molekularem Wasserstoff in Kapselform bei primär biliärer Cholangitis mit erhöhtem IgG4: Ein Fallbericht über die Normalisierung von Immunmarkern", "journal": "In vivo (Athens, Greece)", "authors": "Lin et al.", "author_search": "lin lin", "doi": "10.21873/invivo.13968", "doi_url": "https://doi.org/10.21873/invivo.13968", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40295001/", "url": "https://h2medicine.org/studies/study-lin-2025-capsule-primary-biliary-cholangitis/", "methods": [ "unspecified" ], "indications": [ "liver", "sports-exercise", "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2025 · Lin et al. — Molecular Hydrogen Capsule Therapy for Primary Biliary Cholangitis With Elevated IgG4: A Case Report on Immune Marker Normalization", "summary": "Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease that often responds inadequately to the standard drug ursodeoxycholic acid (UDCA). This case report documents a 44-year-old man with PBC, elevated liver enzymes (AST 279, ALT 183 U/l), and dysregulated immune markers who was started on hydrogen capsule therapy. Over four months, liver enzymes declined substantially and immune checkpoint markers — including KLRG-1, PD-1, and Tim3 — normalized. (In Vivo, 2025.)", "assessment": "Single case report — no control, no placebo, no washout. PBC has well-known fluctuating disease activity, meaning spontaneous improvement between flares is plausible without any intervention. UDCA was continued alongside H₂ capsules, so the additive contribution of H₂ cannot be isolated. The immunological detail (KLRG-1, Tim3, PD-1, IgG4) is the most scientifically interesting aspect, as these markers are mechanistically relevant to autoimmune liver disease. However, without replication in a larger cohort or controlled trial, these findings remain preliminary. Limitation: the H₂ source (capsules) and dose are not described precisely enough for clinical replication.", "abstract": "BACKGROUND/AIM: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by bile duct destruction, cholestasis, and inflammation, often leading to fibrosis and cirrhosis. While ursodeoxycholic acid (UDCA) is the standard treatment, some patients exhibit suboptimal responses, necessitating adjunctive therapies. Molecular hydrogen (H2), known for its antioxidant and anti-inflammatory properties, has shown potential in mitigating oxidative stress and immune dysregulation in autoimmune liver diseases. This case report evaluates the therapeutic efficacy of H2 capsules in managing PBC with elevated liver enzymes and immune dysregulation. CASE REPORT: A 44-year-old male with PBC, splenomegaly, and elevated IgG4 levels presented with acute cholestatic hepatitis. Laboratory tests revealed significantly elevated aspartate transaminase (AST) (279 U/l) and alanine aminotransferase (ALT) (183 U/l). Despite UDCA therapy, liver enzymes remained persistently high. On August 30, 2024, molecular hydrogen capsule therapy was introduced as adjunctive treatment. Over four months, AST and ALT levels declined to 95 U/l and 70 U/l, respectively, without adverse effects. Immune markers (KLRG-1, PD-1, and Tim3), previously reduced during PBC flares, normalized post-treatment. Imaging confirmed stable fibrosis, and IgG4 levels decreased, suggesting reduced autoimmune activity. The patient also reported improvements in fatigue and pruritus, enhancing overall quality of life. CONCLUSION: Molecular hydrogen capsules therapy may serve as a safe and effective adjunctive treatment for PBC, contributing to improved liver enzyme levels, immune regulation, and patient well-being. Further studies are warranted to validate these findings and establish standardized treatment protocols in autoimmune liver diseases.", "conclusion": "Molecular hydrogen capsules therapy may serve as a safe and effective adjunctive treatment for PBC, contributing to improved liver enzyme levels, immune regulation, and patient well-being. Further studies are warranted to validate these findings and establish standardized treatment protocols in autoimmune liver diseases." }, { "pmid": "40259480", "year": 2025, "title": "RNA-Seq Reveals the Mechanism of Synergistic Hydrogen-Chemotherapy Based on Active Magnesium Micromotors for Inhibiting Glioblastoma Recurrence by Modulating Tumor Microenvironment.", "title_en": null, "title_de": "RNA-Seq enthüllt den Mechanismus der synergistischen Wasserstoff-Chemotherapie auf Basis aktiver Magnesium-Mikromotoren zur Hemmung des Glioblastom-Rezidivs durch Modulation der Tumormikroumgebung.", "journal": "Small (Weinheim an der Bergstrasse, Germany)", "authors": "Zhang et al.", "author_search": "zhang zhang", "doi": "10.1002/smll.202408809", "doi_url": "https://doi.org/10.1002/smll.202408809", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40259480/", "url": "https://h2medicine.org/studies/study-zhang-2025-rna-seq-reveals-mechanism/", "methods": [ "inhalation" ], "indications": [ "liver", "neurology", "cancer", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Zhang — RNA-Seq Reveals the Mechanism of Synergistic Hydrogen-Chemotherapy Based on Active Magnesium Micromotors for Inhibiting Glioblastoma Recurrence by Modulating Tumor Microenvironment.", "summary": "Glioblastoma (GBM) almost always returns after surgery — and a new approach using self-propelled magnesium micromotors that generate hydrogen gas locally and simultaneously deliver chemotherapy drug doxorubicin may significantly inhibit this recurrence. In a murine post-surgical GBM model, the combined hydrogen-chemotherapy approach suppressed tumour recurrence and — through RNA-seq analysis — was shown to convert immunologically „cold“ tumours into „hot“ ones, activating the immune system against the cancer. This is an animal study; no human data are available. (Small, 2025.)", "assessment": "An innovative and mechanistically well-characterized preclinical study addressing the clinically urgent problem of GBM recurrence. The dual-function H₂ concept (propulsion + anti-neuroinflammation) is novel, and the RNA-seq immune profiling adds scientific depth. Decisive limitation: this is an animal study — results cannot be directly transferred to human GBM patients. Murine GBM models differ substantially from human tumours in immune biology, and the surgical delivery scenario requires dedicated safety studies. DOX itself is not standard first-line post-operative GBM therapy (temozolomide is), raising questions about clinical fit. A promising mechanistic foundation, not a clinical finding.", "abstract": "Postoperative recurrence of glioblastoma (GBM) is a key contributing factor to the unfavorable prognosis of patients. Chemotherapy has been extensively employed as a postoperative treatment for GBM; however, the produced drug resistance significantly undermines the chemotherapeutic efficacy. Herein, a multifunctional system based on magnesium micromotor (Mg-Motor-DOX) is designed and fabricated that can generate hydrogen gas in situ and actively deliver the chemotherapeutic drug doxorubicin (DOX). Utilizing a temperature-sensitive hydrogel, Mg-Motor-DOX is administrated in situ to the residual cavity of the tumor after subtotal GBM resection. The produced H2 by the Mg-water reaction not only propels the motion of motors but also functions as an antioxidant to effectively alleviate the neuroinflammation caused by GBM resection. The H2 bubbles create a pronounced vortex flow in situ, greatly enhancing the DOX penetration and the sensitivity of GBM cells to DOX. Therefore, synergistic hydrogen-chemotherapy significantly inhibits the recurrence of the in situ GBM model. RNA-Seq technology further elucidates the role of the strategy in modulating the tumor immune microenvironment via converting cold tumors into hot tumors, thereby establishing a theoretical foundation for the clinical implementation of synergistic hydrogen-chemotherapy.", "conclusion": "Therefore, synergistic hydrogen-chemotherapy significantly inhibits the recurrence of the in situ GBM model. RNA-Seq technology further elucidates the role of the strategy in modulating the tumor immune microenvironment via converting cold tumors into hot tumors, thereby establishing a theoretical foundation for the clinical implementation of synergistic hydrogen-chemotherapy." }, { "pmid": "40251018", "year": 2025, "title": "Dietary addition of magnesium hydride nanoparticles: a breakthrough in combating high-fat diet-induced chronic kidney disease.", "title_en": null, "title_de": "Diätetische Zugabe von Magnesiumhydrid-Nanopartikeln: ein Durchbruch bei der Bekämpfung der durch fettreiche Ernährung induzierten chronischen Nierenerkrankung.", "journal": "Medical gas research", "authors": "Lu et al.", "author_search": "lu lu", "doi": "10.4103/mgr.medgasres-d-24-00090", "doi_url": "https://doi.org/10.4103/mgr.medgasres-d-24-00090", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40251018/", "url": "https://h2medicine.org/studies/study-lu-2025-dietary-addition-magnesium-hydride/", "methods": [ "inhalation" ], "indications": [ "metabolic", "kidney-dialysis", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Lu — Dietary addition of magnesium hydride nanoparticles: a breakthrough in combating high-fat diet-induced chronic kidney disease.", "summary": "A high-fat diet gradually damages the kidneys — and feeding mice magnesium hydride (MgH₂) nanoparticles, which release hydrogen gas continuously in the digestive tract, provided significant protection against this kidney damage by reducing fibrosis and inflammation. The study identifies a specific molecular pathway (TGF-β/Smad2/3 inhibition via PTEN upregulation) as the mechanism. This is an animal and cell study — the results are not directly transferable to humans. (Medical Gas Research, 2025.)", "assessment": "A mechanistically thorough preclinical study making a case for dietary MgH₂ nanoparticles as a kidney-protective agent in fat-diet-induced CKD. The identification of the PTEN/TGF-β/Smad2/3 pathway and the additional Hes1 regulatory layer add scientific depth. Decisive limitation: this is animal and cell research — findings cannot be directly applied to humans with CKD. The high-fat diet model does not replicate the full complexity of human CKD (which includes diabetic nephropathy, hypertensive nephropathy, glomerulonephritis, etc.). MgH₂ nanoparticle safety in long-term human oral use has not been established. Clinical trials in humans are an essential prerequisite before any treatment relevance can be claimed.", "abstract": "A substantial body of evidence indicates a positive correlation between dyslipidemia and an elevated risk of chronic kidney disease, with renal interstitial fibrosis frequently serving as a common pathway in the advanced stages of chronic kidney disease progression. Hydrogen has anti-inflammatory and antioxidant properties, and magnesium hydride nanoparticle is a material with high hydrogen storage capacity. Magnesium hydride -fortified feed is capable of releasing hydrogen gas steadily and continuously within the digestive tract. A 12-week high-fat diet significantly elevated the serum urea and creatinine levels in mice. In contrast, dietary addition of magnesium hydride demonstrated a notable protective effect against pathological conditions. Additionally, magnesium hydride -fortified feed was found to reduce renal fibrosis and thereby improve renal function. In support of these findings, an in vitro study utilizing human kidney cortical proximal tubule epithelial cells (HK-2 cells) exposed to palmitic acid under conditions mimicking a high-fat diet confirmed the renoprotective effects of magnesium hydride. Furthermore, the primary target phosphatase and tensin homologue deleted on chromosome 10 and the molecular mechanisms underlying the effects of magnesium hydride, specifically its ability to inhibit the transforming growth factor-beta -Smad family member 2 and 3 (Smad2/3) axis through downregulating the expression of phosphatase and tensin homologue deleted on chromosome 10, were elucidated. Additionally, overexpression of Hes family BHLH transcription factor 1 can negate the beneficial effects of magnesium hydride, suggesting that Hes family BHLH transcription factor 1 may serve as an upstream regulatory target in the context of the effects of magnesium hydride. In conclusion, this study demonstrated that magnesium hydride functions as a safe and effective hydrogen source capable of inhibiting the activation of the transforming growth factor-beta/Smad2/3 and protein kinase B/mechanistic target of rapamycin pathways by increasing the expression of phosphatase and tensin homologue deleted on chromosome 10. This mechanism counteracts the progression of high-fat diet-induced chronic renal damage.", "conclusion": "In conclusion, this study demonstrated that magnesium hydride functions as a safe and effective hydrogen source capable of inhibiting the activation of the transforming growth factor-beta/Smad2/3 and protein kinase B/mechanistic target of rapamycin pathways by increasing the expression of phosphatase and tensin homologue deleted on chromosome 10. This mechanism counteracts the progression of high-" }, { "pmid": "40238879", "year": 2025, "title": "Hydrogen-induced disruption of the airway mucus barrier enhances nebulized RNA delivery to reverse pulmonary fibrosis.", "title_en": null, "title_de": "Wasserstoff-induzierte Störung der Atemwegsschleimbarriere verstärkt die vernebelte RNA-Abgabe zur Umkehrung der Lungenfibrose.", "journal": "Science advances", "authors": "Liu et al.", "author_search": "liu liu", "doi": "10.1126/sciadv.adt2752", "doi_url": "https://doi.org/10.1126/sciadv.adt2752", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40238879/", "url": "https://h2medicine.org/studies/study-liu-2025-induced-disruption-airway-mucus/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "metabolic", "liver", "respiratory" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Liu — Hydrogen-induced disruption of the airway mucus barrier enhances nebulized RNA delivery to reverse pulmonary fibrosis.", "summary": "Pulmonary fibrosis is difficult to treat because the thick mucus lining of airways blocks inhaled medicines from reaching diseased tissue — and molecular hydrogen gas, when delivered simultaneously with aerosolised RNA therapy, disrupts this mucus barrier through physical shear forces, dramatically improving drug penetration into fibrotic lungs. In mice, the combined approach effectively blocked fibrotic signalling pathways and reversed lung scarring. This is an animal study; no human data are available. (Science Advances, 2025.)", "assessment": "A highly innovative and technically sophisticated preclinical study that repositions H₂ from a purely antioxidant role to a physical drug-delivery enhancer — using gas-flow shear stress to overcome the mucus barrier in fibrotic lungs. The dual functionality (H₂ as therapeutic + H₂ as delivery enhancer) is conceptually novel. Critical limitation: this is entirely animal research — no human data exist, and results cannot be extrapolated to patients. The custom aerosol inhalation device and the hybrid LNP design require substantial engineering and safety validation for human use. RNA therapy in PF is itself still in early clinical stages. A compelling mechanistic advance requiring extensive further development before any clinical relevance.", "abstract": "Nebulized RNA therapies are well suited for treating respiratory diseases, in particular pulmonary fibrosis (PF); however, effective delivery remains challenging. In this study, we present a highly efficient aerosol inhalation system that enables high levels of in vivo transfection efficiency in lung macrophages, yielding durable responses against PF. First, we established a nose-only aerosol inhalation device integrated with a hydrogen supplement system. This setup enables the precise administration of lipid nanoparticles (LNPs) at a controlled low dose, while simultaneously delivering the optimal concentration of therapeutic hydrogen gas. We further developed a hybrid lipid NP (HNP) by hybridizing a pH-dependent charge-inverting lipid film with apoptotic T cell membranes to enhance endosomal escape and trigger macrophage production of hepatocyte growth factor for lung repair. We demonstrated that the hydrogen flow-induced shear stresses disrupt the NP-mucus interaction, enhancing the deposition of aerosolized HNPs/TGFβ1 siRNA within fibrotic lung lesions, effectively blocking fibrogenic signaling pathways and offering a clinically viable strategy for combating PF.", "conclusion": "We further developed a hybrid lipid NP (HNP) by hybridizing a pH-dependent charge-inverting lipid film with apoptotic T cell membranes to enhance endosomal escape and trigger macrophage production of hepatocyte growth factor for lung repair. We demonstrated that the hydrogen flow-induced shear stresses disrupt the NP-mucus interaction, enhancing the deposition of aerosolized HNPs/TGFβ1 siRNA withi" }, { "pmid": "40189120", "year": 2025, "title": "A partially degradable composite consisting of Ti-Zr-Cu-Pd-Sn metallic glass and Fe-Mg alloy for orthopedic applications.", "title_en": null, "title_de": "Ein teilweise abbaubarer Verbundwerkstoff aus metallischem Ti-Zr-Cu-Pd-Sn-Glas und Fe-Mg-Legierung für orthopädische Anwendungen.", "journal": "Acta biomaterialia", "authors": "Du et al.", "author_search": "du du", "doi": "10.1016/j.actbio.2025.04.011", "doi_url": "https://doi.org/10.1016/j.actbio.2025.04.011", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40189120/", "url": "https://h2medicine.org/studies/study-du-2025-partially-degradable-composite-consisting/", "methods": [ "inhalation" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Du — A partially degradable composite consisting of Ti-Zr-Cu-Pd-Sn metallic glass and Fe-Mg alloy for orthopedic applications.", "summary": "Researchers combined a titanium-based metallic glass with an iron-magnesium alloy into a novel partially degradable bone implant. The Fe-Mg component gradually dissolves and is replaced by newly formed bone, while the metallic-glass skeleton remains. The design addresses two key problems: the slow degradation of iron and the rapid breakdown of magnesium — both of which had previously caused excessive hydrogen gas build-up that could fracture surrounding bone. (Acta Biomaterialia, 2025.)", "assessment": "This is an in-vitro materials-science study — not a hydrogen therapy study in the clinical sense. H₂ appears here as a degradation by-product to be controlled, not as a therapeutic molecule. Results on cell viability and mechanical properties come from laboratory models and cannot be directly transferred to clinical outcomes in humans. The work is technically solid and addresses a genuine problem in biodegradable implant design, but clinical validation in animals and humans is still required.", "abstract": "Partially-degradable biomaterials refers to smart implants where biodegradable metals can gradually be replaced by newly growing bone or living tissues, and leave behind a porous inert metal skeleton that stably binds with the new bone tissue. In this research, a partially degradable composite was designed by integrating Ti-Zr-Cu-Pd-Sn metallic glass (MG) with designed Fe-Mg alloy using spark plasma sintering (SPS). The mechanical alloying technique successfully enabled the fusion of immiscible Fe and Mg, addressing the issues of Fe's slow degradation and Mg's rapid breakdown, while also minimizing potential fractures in the metal framework due to hydrogen gas evolution. The controlled degradation of Mg(Fe) promotes the formation of Ca-P compounds, enhancing the bioactivity of the Fe-Mg composite. This design endows the composite with plastic and ductile deformation under compression, providing a viable solution to the brittle fracture behaviour commonly associated with conventional bulk metallic glasses (BMGs). This advancement holds promise for aligning with the natural growth rate of human bone, further augmenting the bioactive properties and practical applications of the MG/Fe-Mg composite material. STATEMENT OF SIGNIFICANCE: In this research, a partially degradable composite was designed by integrating Ti-Zr-Cu-Pd-Sn metallic glass (MG) with designed Fe-Mg alloy using SPS. The Fe-Mg alloy act as temporary space holders can gradually being replaced by newly formed bone, thus establishing a dynamic equilibrium between the biodegradation of the bio-metals and the inward growth of new bone. The degradation of Mg(Fe) promotes the formation of Ca-P compounds, enhancing the bioactivity of the composite. This design endows the composite with plastic deformation under compression, providing a viable solution to the brittle fracture behavior of conventional MGs. This advancement holds promise for aligning with the natural growth rate of human bone, further augmenting the practical applications of the MG/Fe-Mg composite.", "conclusion": "This design endows the composite with plastic deformation under compression, providing a viable solution to the brittle fracture behavior of conventional MGs. This advancement holds promise for aligning with the natural growth rate of human bone, further augmenting the practical applications of the MG/Fe-Mg composite." }, { "pmid": "40077785", "year": 2025, "title": "Hydrogen and Methane Detection in Breath in Response to Two Different Types of Dietary Fiber and Its Relationship to Postprandial Glucose Concentration in Obese Patients with Type 2 Diabetes and Normoglycemic Subjects.", "title_en": null, "title_de": "Wasserstoff- und Methannachweis in der Atemluft als Reaktion auf zwei verschiedene Ballaststoffarten und dessen Zusammenhang mit der postprandialen Glukosekonzentration bei adipösen Patienten mit Typ-2-Diabetes und normoglykämischen Probanden", "journal": "Nutrients", "authors": "Misnikova et al.", "author_search": "misnikova misnikova", "doi": "10.3390/nu17050917", "doi_url": "https://doi.org/10.3390/nu17050917", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40077785/", "url": "https://h2medicine.org/studies/study-misnikova-2025-methane-detection-breath-response/", "methods": [], "indications": [ "diabetes", "metabolic" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "breath-test", "headline": "2025 · Misnikova et al. — Hydrogen and Methane Detection in Breath in Response to Two Different Types of Dietary Fiber and Its Relationship to Postprandial Glucose Concentration in Obese Patients with Type 2 Diabetes and Normoglycemic Subjects", "summary": "This study reveals a striking difference in gut-produced H₂ between people with type 2 diabetes (T2DM) and metabolically healthy controls. After eating fiber-rich foods, normoglycemic participants produced significantly more exhaled H₂ — and those with higher H₂ showed lower postprandial glucose spikes. Patients with T2DM produced less H₂ but more methane (CH₄), and methane correlated positively with worse glucose control. (Nutrients, 2025.)", "assessment": "This is a small exploratory study (n=28) without intervention — it does not test H₂ supplementation and makes no claims about drinking H₂-enriched water. The correlation between exhaled H₂ and postprandial glycemia is statistically significant but based on a small sample. Causality is not established — lower H₂ in T2DM may be a consequence of altered microbiome composition rather than a driver of glucose dysregulation. The methane-glycemia correlation in T2DM, while intriguing, involves small subgroups. Important framing note: this study is about gut-produced H₂ as a microbiome marker, not about therapeutic H₂ administration. It is nonetheless relevant context for understanding why some individuals may respond differently to H₂ therapy.", "abstract": "Background: The aim of this study was to investigate the relationship between postprandial glycemic levels based on flashmonitoring and the production of intestinal hydrogen (H2) and methane (CH4) gases based on the measurement of the amount of these gases in exhaled air. Materials and Methods: We studied 14 subjects with type 2 diabetes mellitus (T2DM) and 14 individuals without diabetes (control) with two food load tests, including two types of dietary fiber (inulin and guar gum), with the simultaneous determination of gases in exhaled air and the assessment of glucose levels. Results: All subjects in the control group had a significant increase in exhaled H2. OR for increased hydrogen production in patients with T2DM was 0.17 (95% CI 0.031-0.93, p = 0.043). The level of H2 in exhaled breath after food load in patients with T2DM was lower than in normoglycemic subjects. There was an inverse correlation between maximum glucose rise and maximum H2 in exhaled air after food load in normoglycemic subjects (r = -0.569, p = 0.034). Patients with T2DM had direct correlations between the level of CH4 in exhaled air and the parameters of postprandial glycemia in the lactulose test (p < 0.05). Conclusions: The confirmation of a causal relationship between decreased H2 production, increased intestinal CH4 production, and more severe postprandial glycemia may identify new therapeutic targets in the correction of postprandial glycemia in patients with T2DM.", "conclusion": "The confirmation of a causal relationship between decreased H2 production, increased intestinal CH4 production, and more severe postprandial glycemia may identify new therapeutic targets in the correction of postprandial glycemia in patients with T2DM." }, { "pmid": "40066473", "year": 2025, "title": "Galvanic Cell Bipolar Microneedle Patches for Reversing Photoaging Wrinkles.", "title_en": null, "title_de": "Galvanische bipolare Mikronadel-Pflaster zur Umkehrung von Photoalterungs-Falten.", "journal": "Advanced materials (Deerfield Beach, Fla.)", "authors": "Lin et al.", "author_search": "lin lin", "doi": "10.1002/adma.202500552", "doi_url": "https://doi.org/10.1002/adma.202500552", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40066473/", "url": "https://h2medicine.org/studies/study-lin-2025-galvanic-cell-bipolar-microneedle/", "methods": [ "inhalation" ], "indications": [ "cancer", "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Lin — Galvanic Cell Bipolar Microneedle Patches for Reversing Photoaging Wrinkles.", "summary": "A microneedle patch containing magnesium-based bipolar electrodes generates microcurrents and releases hydrogen gas and magnesium ions directly in the skin via a galvanic cell reaction. In animal experiments, the combined effect of H₂'s antioxidant and anti-inflammatory properties, microcurrent-stimulated cell migration, and magnesium's support for blood-vessel formation successfully reversed UV-induced skin photoaging wrinkles. (Advanced Materials, 2025.)", "assessment": "This is a preclinical animal study — results cannot be directly transferred to humans. The concept of combining H₂ delivery with microcurrents and magnesium ions via a dissolvable microneedle patch is original, and the multi-pathway approach to reversing UV-induced wrinkles is mechanistically well-argued. However, all efficacy data come from mouse models, and H₂ is only one of several active components tested jointly. Independent replication and controlled human trials are necessary before drawing conclusions about effectiveness in cosmetic or medical skin care.", "abstract": "Excessive exposure to ultraviolet (UV) radiation is a major factor in the development of skin photoaging wrinkles. While current treatments can slow the progression of photoaging, it is very difficult to achieve complete reversal. This study introduces galvanic cell microneedle (GCMN) patches with magnesium-containing bipolar electrodes. These patches operate through a galvanic cell mechanism, generating microcurrents and releasing hydrogen gas and magnesium ions via a redox reaction. The combination of hydrogen's antioxidant and anti-inflammatory properties, microcurrent-induced stimulation of cell migration, and magnesium's promotion of angiogenesis and macrophage M2 anti-inflammatory polarization synergistically works to reverse photoaging wrinkles and rejuvenate the skin. Furthermore, this work examines how GCMNs may influence the transforming growth factor-β/Smad (TGF-β/Smad) pathway. This approach shows promise for advancing research and development in the field of medical cosmetology.", "conclusion": "Furthermore, this work examines how GCMNs may influence the transforming growth factor-β/Smad (TGF-β/Smad) pathway. This approach shows promise for advancing research and development in the field of medical cosmetology." }, { "pmid": "40010997", "year": 2025, "title": "Molecular Hydrogen Therapy Enhances Immune Markers in Treg, Plasma, Tr1 Cells, and KLRG1 Expression on Tc Cells: A Case of Acute SDH With Midline Shift and Uncal Herniation Post-decompressive Craniectomy.", "title_en": null, "title_de": "Therapie mit molekularem Wasserstoff verstärkt Immunmarker in Treg-, Plasma-, Tr1-Zellen und die KLRG1-Expression auf Tc-Zellen: Ein Fall von akutem Subduralhämatom mit Mittellinienverlagerung und Unkusherniation nach dekompressiver Kraniektomie", "journal": "In vivo (Athens, Greece)", "authors": "Hsu et al.", "author_search": "hsu hsu", "doi": "10.21873/invivo.13923", "doi_url": "https://doi.org/10.21873/invivo.13923", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40010997/", "url": "https://h2medicine.org/studies/study-hsu-2025-enhances-immune-markers-treg/", "methods": [ "unspecified" ], "indications": [ "sports-exercise", "neurology", "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2025 · Hsu et al. — Molecular Hydrogen Therapy Enhances Immune Markers in Treg, Plasma, Tr1 Cells, and KLRG1 Expression on Tc Cells: A Case of Acute SDH With Midline Shift and Uncal Herniation Post-decompressive Craniectomy", "summary": "Acute subdural hematoma with brain herniation carries high mortality and poor neurological outcomes. This case report describes a 24-year-old man who survived a severe traumatic SDH — with midline shift, uncal herniation, and dilated pupil — and received hydrogen capsules as an add-on to conventional neurocritical care. The primary recovery was attributed to standard interventions, but H₂ therapy appeared to favorably modulate immune markers, particularly regulatory T cells and plasma cells, without adverse effects. (In Vivo, 2025.)", "assessment": "Single case report with four simultaneous major interventions — any attribution to H₂ is speculative. The patient received craniectomy, hyperbaric oxygen (itself a strong anti-inflammatory), therapeutic hypothermia, and stem cell therapy concurrently. These are each individually capable of modulating the immune profile described. The H₂ contribution cannot be isolated. The authors are appropriately cautious. The clinical value of this report is primarily in demonstrating safety (no adverse effects) and in providing an immunological snapshot of a neurotrauma patient during H₂ therapy — a niche that is essentially unexplored. This does not constitute efficacy evidence for H₂ in neurotrauma.", "abstract": "BACKGROUND/AIM: Subdural hematomas (SDH), often caused by head trauma, are serious with high mortality and long-term complications. Studies show that molecular hydrogen has neuroprotective effects, such as reducing oxidative stress, inflammation, and cell death. It may also protect mitochondria, support cell function, and regulate immune responses, making it a promising new treatment option for SDH. However, more research is needed to confirm its effectiveness and create treatment guidelines. CASE REPORT: We present a 24-year-old man with SDH, along with a right-sided midline shift, uncal herniation, and dilated left pupil. Conventional treatments-craniectomy, hyperbaric oxygen, therapeutic hypothermia, and stem cell therapy-were essential for stabilizing his condition. In addition, we administered hydrogen capsules as a novel adjunct therapy, beginning daily treatment immediately upon admission. While recovery was primarily due to standard interventions, hydrogen therapy appeared to enhance immune markers, particularly Treg and plasma cells, with no adverse effects. This case indicates that hydrogen therapy may serve as a beneficial addition to established SDH management methods. CONCLUSION: This case suggests that molecular hydrogen therapy may be a helpful adjunct treatment for SDH with midline shift. Conventional therapies, including craniectomy, hyperbaric oxygen, therapeutic hypothermia, and stem cell therapy, were vital to the patient's recovery, but hydrogen therapy may have contributed by modulating immune responses, particularly Treg and plasma cell activity. While these findings are encouraging, further research is necessary to confirm hydrogen therapy's benefits and its role alongside traditional neurocritical care treatments.", "conclusion": "This case suggests that molecular hydrogen therapy may be a helpful adjunct treatment for SDH with midline shift. Conventional therapies, including craniectomy, hyperbaric oxygen, therapeutic hypothermia, and stem cell therapy, were vital to the patient's recovery, but hydrogen therapy may have contributed by modulating immune responses, particularly Treg and plasma cell activity. While these findings are encouraging, further research is necessary to confirm hydrogen therapy's benefits and its r" }, { "pmid": "40010970", "year": 2025, "title": "Molecular Hydrogen Therapy for SLE-PAH: Case Report on Immune Marker Modulation.", "title_en": null, "title_de": "Therapie mit molekularem Wasserstoff bei SLE-PAH: Fallbericht über die Modulation von Immunmarkern", "journal": "In vivo (Athens, Greece)", "authors": "Tu et al.", "author_search": "tu tu", "doi": "10.21873/invivo.13926", "doi_url": "https://doi.org/10.21873/invivo.13926", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40010970/", "url": "https://h2medicine.org/studies/study-tu-2025-sle-pah-immune-marker/", "methods": [ "unspecified" ], "indications": [ "cardiovascular", "respiratory", "immune-system" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2025 · Tu et al. — Molecular Hydrogen Therapy for SLE-PAH: Case Report on Immune Marker Modulation", "summary": "SLE-associated pulmonary arterial hypertension (SLE-PAH) is one of the most life-threatening complications of lupus, and standard vasodilator treatments often fail to adequately control progression. This case report documents a 51-year-old woman with SLE-PAH who had worsening disease since 2018 — including severe dyspnea and oxygen desaturation following sepsis — and showed clinical stabilization after molecular hydrogen therapy was introduced in 2024. (In Vivo, 2025.)", "assessment": "This is a single case report in an extremely rare and severe condition. The clinical „stabilization“ observed may reflect natural disease fluctuation in PAH rather than a H₂ effect — PAH severity can vary over weeks to months without treatment changes. The immune phenotyping is detailed but cannot establish causality at n=1. The Tr1/Treg ratio change is biologically interesting — Tr1 cells (IL-10 secreting, anti-inflammatory) increasing while Tregs decrease could suggest a shift in immune regulatory balance, but this requires mechanistic follow-up. No hemodynamic data (right heart catheterization, echocardiographic measurements) are reported, which are the gold standard for PAH assessment. Safety signal is reassuring; efficacy remains unproven.", "abstract": "BACKGROUND/AIM: Systemic lupus erythematosus-associated pulmonary arterial hypertension (SLE-PAH) is a severe complication marked by elevated pulmonary artery pressure, leading to exertional dyspnea and right-sided heart failure. Standard treatments frequently fall short in effectively controlling symptoms, highlighting the need for innovative therapeutic approaches. This aim of this study was to investigate the efficacy of molecular hydrogen therapy in a patient with SLE-PAH with decompensated right-side heart failure. CASE REPORT: We present the case of a 51-year-old female diagnosed with SLE-PAH in 2012. Despite treatment with vasodilator agents, her condition worsened following an episode of sepsis, leading to severe dyspnea and oxygen desaturation since 2018. In March 2024, molecular hydrogen therapy was introduced as an adjuvant treatment. The patient received daily hydrogen capsules, which resulted in an increased percentage of Tr1 cells, and a decreased percentage of Treg cell subsets, B cell subsets, marginal cell, and plasma cell. Her clinical symptoms stabilized, and no adverse effects or complications were observed. CONCLUSION: This case study highlights the potential efficacy of molecular hydrogen therapy in a patient with SLE-PAD and decompensated right-sided heart failure precipitated by sepsis. Further research is needed to confirm its therapeutic benefits, particularly its ability to modulate immune markers and improve clinical outcomes.", "conclusion": "This case study highlights the potential efficacy of molecular hydrogen therapy in a patient with SLE-PAD and decompensated right-sided heart failure precipitated by sepsis. Further research is needed to confirm its therapeutic benefits, particularly its ability to modulate immune markers and improve clinical outcomes." }, { "pmid": "40010949", "year": 2025, "title": "Molecular Hydrogen as an Adjuvant Therapy in Severe Lupus Serositis With Heart Failure: A Case Report on Immune Modulation and Fatigue Reduction.", "title_en": null, "title_de": "Molekularer Wasserstoff als adjuvante Therapie bei schwerer Lupus-Serositis mit Herzinsuffizienz: Ein Fallbericht über Immunmodulation und Reduktion der Ermüdung", "journal": "In vivo (Athens, Greece)", "authors": "Lin et al.", "author_search": "lin lin", "doi": "10.21873/invivo.13924", "doi_url": "https://doi.org/10.21873/invivo.13924", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40010949/", "url": "https://h2medicine.org/studies/study-lin-2025-adjuvant-severe-lupus-serositis/", "methods": [ "unspecified" ], "indications": [ "sports-exercise", "cardiovascular", "immune-system", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2025 · Lin et al. — Molecular Hydrogen as an Adjuvant Therapy in Severe Lupus Serositis With Heart Failure: A Case Report on Immune Modulation and Fatigue Reduction", "summary": "SLE with cardiac complications is managed with steroids and immunomodulators — but prolonged use causes serious side effects. This case documents a 51-year-old woman with SLE and acute decompensated heart failure who, after adding molecular hydrogen therapy to her regimen, showed improved cardiac function, reduced autoantibody levels, favorable immune shifts, and significant fatigue reduction — while successfully tapering off steroids. (In Vivo, 2025.)", "assessment": "A single case report with background immunomodulator therapy ongoing throughout. The documented improvements (autoantibody reduction, Pro-BNP reduction, steroid taper, fatigue improvement) are clinically meaningful outcomes — but each can occur during natural SLE remission cycles, as a delayed response to prior therapy, or due to the background immunomodulator itself. H₂ cannot be credited or debited independently. The value of this case lies in illustrating the safety of H₂ as a concurrent therapy and in generating hypotheses about H₂'s potential steroid-sparing role in SLE — a question that merits a dedicated randomized trial. The authors themselves call for further studies.", "abstract": "BACKGROUND/AIM: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multi-organ inflammation and damage across multiple organs, typically managed with steroids and immunomodulators. However, prolonged use of these treatments is often associated with significant side effects, underscoring the need for adjunctive therapies that improve disease outcomes while minimizing adverse effects. Molecular hydrogen (H2) has demonstrated potential as an antioxidant and anti-inflammatory agent. This report discusses a case of SLE with cardiac complications, evaluating the therapeutic impact of molecular hydrogen therapy on fatigue, immune modulation, and cardiac function. CASE REPORT: A 51-year-old female with SLE and acute decompensated heart failure initially received steroids and immunomodulators for disease management. Subsequently, molecular hydrogen therapy was introduced as an adjuvant treatment. Over several months, her cardiac function showed notable improvement, evidenced by reductions in anti-dsDNA and anti-Ro52 antibody levels, and Pro-BNP levels, as well as favorable shifts in T and B cell subsets. Additionally, the patient experienced a significant reduction in fatigue. She successfully tapered off steroids while maintaining disease stability with ongoing molecular hydrogen therapy. CONCLUSION: This case highlights the potential of molecular hydrogen therapy as an adjuvant treatment in SLE, with observed benefits in immune modulation and fatigue reduction. Further studies are warranted to elucidate its therapeutic role and applicability in autoimmune diseases.", "conclusion": "This case highlights the potential of molecular hydrogen therapy as an adjuvant treatment in SLE, with observed benefits in immune modulation and fatigue reduction. Further studies are warranted to elucidate its therapeutic role and applicability in autoimmune diseases." }, { "pmid": "39969918", "year": 2025, "title": "Performance of Unmodified Mechanical Ventilators With 2% Hydrogen Gas Mixtures.", "title_en": null, "title_de": "Leistung unmodifizierter mechanischer Beatmungsgeräte mit 2%-Wasserstoffgasgemischen.", "journal": "Respiratory care", "authors": "Mancebo et al.", "author_search": "mancebo mancebo", "doi": "10.4187/respcare.12371", "doi_url": "https://doi.org/10.4187/respcare.12371", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39969918/", "url": "https://h2medicine.org/studies/study-mancebo-2025-performance-unmodified-mechanical-ventilators/", "methods": [ "inhalation" ], "indications": [ "liver", "sports-exercise", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Mancebo — Performance of Unmodified Mechanical Ventilators With 2% Hydrogen Gas Mixtures.", "summary": "Can standard, unmodified intensive-care ventilators safely deliver a 2% H₂ gas mixture? This in-vitro bench study tested four clinical ventilator models and found that three (Servo-i, Servo-u, Evita V500) delivered the mixture with acceptable accuracy for both tidal volume and oxygen concentration — while the neonatal Babylog VN500 showed severe inaccuracies in tidal volume delivery and should not be used with H₂ mixtures without modification. (Respiratory Care, 2025.)", "assessment": "This is a device-performance in-vitro study with no data on patient outcomes or H₂ efficacy — it tests hardware compatibility only. The finding that three common adult ventilators can deliver 2% H₂ accurately is an important practical step for future clinical research. However, the study does not address clinical benefit, safety in patients, or optimal H₂ dosing. Clinicians and researchers should take the Babylog VN500 warning seriously for neonatal/paediatric applications. This study tells us about ventilator mechanics, not about therapeutic effects of H₂ in humans.", "abstract": "Background: Molecular hydrogen (H2) is a breathable gas that has been shown to have anti-oxidative, anti-inflammatory, and anti-apoptotic properties that may positively impact ischemia-reperfusion injury. The provision of 2% H2 through unmodified mechanical ventilators may facilitate the clinical translation of H2 as a therapeutic in critical illness. The effect of 2% H2 on ventilator performance is unknown. Methods: Unmodified Maquet Servo-i, Maquet Servo-u, Dräger Evita Infinity V500, and Dräger Evita Babylog VN500 ventilators from clinical stock were tested in an experimental closed system using certified, premixed air and O2 containing 2% H2 gas. Wall air and O2 supply were used as control. Ventilator settings were varied across the spectrum of neonatal to adult settings. End points included (1) difference between set and delivered tidal volume (VT) (Douglas method), (2) difference between set versus delivered O2 concentration, (3) delivered H2 concentration (gas chromatography), and (4) ventilator pre-use check malfunction. Correlation between set and measured end points were quantified by linear regression analysis and bias by Bland-Altman analysis. Results: During H2 administration, the average bias in measured versus set VT was within ± 10% for all ventilators except for the Babylog VN500, which exhibited an average bias of -89.2% (95% CI -107.0 to -71.3). The average bias in measured FIO2 was within ± 10% of set for all ventilators. Except for the Babylog VN500, all ventilators passed the pre-use check. Conclusions: Unmodified Servo-i, Servo-u, and Evita V500 ventilators deliver 2% H2 mixtures with acceptable accuracy in VT and FIO2. The Babylog VN500, which uses hot-wire anometry and a higher set operating temperature, exhibits unacceptably inaccurate delivery of VT with H2 mixtures.", "conclusion": "Unmodified Servo-i, Servo-u, and Evita V500 ventilators deliver 2% H2 mixtures with acceptable accuracy in VT and FIO2. The Babylog VN500, which uses hot-wire anometry and a higher set operating temperature, exhibits unacceptably inaccurate delivery of VT with H2 mixtures." }, { "pmid": "39934143", "year": 2025, "title": "Hemodialysis employing molecular hydrogen (H2) enriched dialysis solution may improve dialysis related fatigue through impact on energy metabolism.", "title_en": null, "title_de": "Hämodialyse mit molekularem Wasserstoff (H₂)-angereicherter Dialyselösung könnte die dialysebedingte Ermüdung durch Einfluss auf den Energiestoffwechsel verbessern", "journal": "Scientific reports", "authors": "Nakayama et al.", "author_search": "nakayama nakayama", "doi": "10.1038/s41598-025-88827-2", "doi_url": "https://doi.org/10.1038/s41598-025-88827-2", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39934143/", "url": "https://h2medicine.org/studies/study-nakayama-2025-hemodialysis-employing-enriched-dialysis/", "methods": [ "unspecified" ], "indications": [ "metabolic", "sports-exercise", "kidney-dialysis" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2025 · Nakayama et al. — Hemodialysis Employing Molecular Hydrogen (H₂) Enriched Dialysis Solution May Improve Dialysis-Related Fatigue Through Impact on Energy Metabolism", "summary": "Fatigue is one of the most debilitating aspects of life on hemodialysis — and it remains largely unaddressed by standard care. This prospective study of 81 hemodialysis patients over 12 months found that H₂-enriched electrolytic hemodialysis (E-HD) significantly reduced fatigue specifically in patients who had fatigue with activity reduction at baseline, while patients without fatigue remained unaffected. Metabolic pathway analysis points to altered energy metabolism — fatty acid metabolism, citric acid cycle, glycolysis — as a possible mechanism. (Scientific Reports, 2025.)", "assessment": "This is the strongest study in this batch — prospective, n=81, 12-month follow-up, metabolomics, body composition — though it lacks a randomized control arm. All patients received E-HD (no standard HD comparison), so the improvement in Group A cannot be attributed exclusively to H₂ versus other aspects of the treatment protocol. The subgroup finding is biologically coherent and the metabolomics data provide mechanistic depth. Honest note on body composition: the significant reduction in body fat and increase in muscle mass in Group A2 (fatigue only on dialysis days) without significant weight change is a surprising and potentially important finding that deserves independent replication. The authors' claim of a „new paradigm“ is aspirational but not unreasonable given the biological plausibility and 12-month durability of the effect.", "abstract": "Hemodialysis employing molecular hydrogen (H2)-enriched dialysis solution rendered by water electrolysis (E-HD), has been reported to alleviate dialysis-related fatigue, but its association with metabolic profiles remains unclear. Eighty-one patients undergoing standard HD were classified into 3 groups [Group A (n = 25, 30.9%): fatigue with activity reduction-subgroups A1: chronic persistent fatigue (n = 11), A2: fatigue only on dialysis days (n = 14); Group B: fatigue without activity reduction (n = 24, 29.6%); Group C (n = 32, 39.5%): no fatigue], and their changes in fatigue, body composition, and metabolic profiles were studied following 12 months of E-HD. There were no significant differences in baseline characteristics among the groups. Over the 12 months after E-HD initiation, fatigue in Group A significantly decreased, while no changes in Group-B and C. Bio-impedance analysis revealed no significant changes in A1, but significant reductions in body fat and increases in skeletal muscle mass were observed despite no significant weight change in A2. Enrichment analysis suggested significant differences in metabolic pathways such as fatty acid metabolism, citric acid cycle, and glycolysis between Groups A and C at baseline, and these differences were mitigated by E-HD. E-HD could suppress dialysis-related fatigue, through possible involvement of altered energy metabolism of patients. E-HD may represent a new paradigm for uremia treatment beyond traditional solute removal-based dialysis therapies.", "conclusion": "E-HD could suppress dialysis-related fatigue, through possible involvement of altered energy metabolism of patients. E-HD may represent a new paradigm for uremia treatment beyond traditional solute removal-based dialysis therapies." }, { "pmid": "39921438", "year": 2025, "title": "Ternary Schottky Junction for Sonocatalytic Water Splitting in Gas-Immunotherapy-Mediated Cancer Treatment.", "title_en": null, "title_de": "Ternärer Schottky-Übergang zur sonokatalytischen Wasserspaltung in der gas-immuntherapie-vermittelten Krebsbehandlung.", "journal": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)", "authors": "Zhang et al.", "author_search": "zhang zhang", "doi": "10.1002/advs.202413519", "doi_url": "https://doi.org/10.1002/advs.202413519", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39921438/", "url": "https://h2medicine.org/studies/study-zhang-2025-ternary-schottky-junction-sonocatalytic/", "methods": [ "unspecified" ], "indications": [ "cancer", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Zhang — Ternary Schottky Junction for Sonocatalytic Water Splitting in Gas-Immunotherapy-Mediated Cancer Treatment.", "summary": "A specially designed nanoparticle catalyst (BPM) splits water inside tumours using ultrasound, generating both hydrogen and oxygen in situ. In animal experiments, this local H₂ and O₂ production disrupted cancer-cell energy metabolism, amplified immune responses, and combined effectively with immune checkpoint blockade to suppress both the treated tumour and distant metastases. (Advanced Science, 2025.)", "assessment": "This is a preclinical animal study; results from mouse tumour models cannot be directly transferred to humans. The sonocatalytic gas-immunotherapy concept is novel and mechanistically ambitious, combining H₂ therapy, reactive-oxygen-species manipulation, immune activation, and checkpoint blockade in a single platform. However, translational barriers are substantial: nanoparticle safety, biodistribution, ultrasound accessibility of deep tumours, and immune-related toxicity all require extensive further study. No human data exist for this approach.", "abstract": "Hydrogen therapy has shown new potential in cancer treatment, particularly in high-pressure and hypoxic areas, where it demonstrates the ability to alter the tumor microenvironment and regulate tumor metabolism. Hydrogen disrupts the mitochondrial function of cancer cells, interferes with their energy metabolism, and ultimately leads to energy depletion and apoptosis. In this study, a sonocatalyst (BPM), is designed to generate hydrogen and oxygen in situ within tumors, further enhancing the therapeutic efficacy. The mesocrystalline structure of BPM, composed of bismuth fluoride, polyoxometalates, and molybdenum carbide, significantly improves charge separation and electron transfer efficiency under ultrasound irradiation, resulting in an efficient water-splitting reaction. By simultaneously generating hydrogen and oxygen within the tumor microenvironment and depleting glutathione, BPM effectively triggers oxidative stress and alleviates hypoxia, thereby disrupting mitochondrial function and inhibiting energy metabolism in cancer cells. Additionally, BPM enhances antitumor immune responses by promoting dendritic cell maturation, activating T lymphocytes, and polarizing macrophages toward the M1 phenotype, reversing the immunosuppressive state of the tumor microenvironment. The results indicate that BPM holds potential for gas-immunotherapy combination treatments, offering a multifunctional strategy to improve cancer therapy outcomes.", "conclusion": "Additionally, BPM enhances antitumor immune responses by promoting dendritic cell maturation, activating T lymphocytes, and polarizing macrophages toward the M1 phenotype, reversing the immunosuppressive state of the tumor microenvironment. The results indicate that BPM holds potential for gas-immunotherapy combination treatments, offering a multifunctional strategy to improve cancer therapy outco" }, { "pmid": "39838815", "year": 2025, "title": "A Sustained H2/Fluorouracil-Releasing Suppository for High-efficacy and Low-Toxicity Hydrogenochemotherapy of Colon Cancer.", "title_en": null, "title_de": "Ein H₂/Fluorouracil-freisetzendes Suppositorium mit anhaltender Wirkung für die hocheffiziente und niedertoxische Hydrogeno-Chemotherapie von Dickdarmkrebs.", "journal": "Advanced healthcare materials", "authors": "Chen et al.", "author_search": "chen chen", "doi": "10.1002/adhm.202404054", "doi_url": "https://doi.org/10.1002/adhm.202404054", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39838815/", "url": "https://h2medicine.org/studies/study-chen-2025-sustained-fluorouracil-releasing-suppository/", "methods": [ "unspecified" ], "indications": [ "cancer", "oxidative-stress", "fundamentals-safety" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Chen — A Sustained H₂/Fluorouracil-Releasing Suppository for High-efficacy and Low-Toxicity Hydrogenochemotherapy of Colon Cancer.", "summary": "Combining hydrogen gas with the standard chemotherapy drug 5-fluorouracil in a rectal suppository achieved complete tumour eradication in a mouse colon-cancer model — while simultaneously protecting the intestinal tissue from chemotherapy-induced damage. The hydrogen, released from cerium silicide nanoparticles in the suppository, scavenged excess reactive oxygen species in healthy cells and helped cancer cells undergo apoptosis via a separate pathway. (Advanced Healthcare Materials, 2025.)", "assessment": "This is a preclinical animal study — results from a mouse colon-cancer model cannot be directly transferred to humans. The dual-action design (protecting normal tissue + enhancing tumour kill) is scientifically elegant and addresses a real clinical problem of chemotherapy intestinal toxicity. The CO co-release adds another mechanistic layer that requires independent safety characterisation. No human data exist; clinical translation requires extensive safety and pharmacokinetic studies. The result of complete tumour eradication, while striking, should be interpreted cautiously as it applies to one mouse tumour model only.", "abstract": "To attenuate the intestinal toxicity of chemotherapeutic drugs from rectal suppositories and enhance their chemotherapeutic outcome is greatly significant, but maintains a challenge. In this work, a new strategy of local synergistic hydrogenochemotherapy is proposed to attenuate side effects and enhance therapeutic efficacy based on the anti-cancer selectivity and normal cells-protecting effect of H2, and construct a novel anti-cancer formulation of rectal suppository (5-FU/CSN@FAG) by fatty acid glycerides (FAG) encapsulating 5-fluorouracil (5-FU, a first-line drug for colorectal cancer treatment) and cerium silicide nanoparticles (CSN) with a sustained hydrolytic H2 release behavior which is synchronous with 5-FU release. The 3-week treatment with the suppository once a day can not only completely eradicate colon tumors without tumor recurrence after suppository administration withdrawal, but also efficiently protect the intestinal tract from chemotherapeutic damage. Mechanistically, H2 generated by CSN reduces the toxicity of 5-FU to normal cells in the intestinal tract by scavenging over-expressed reactive oxygen species and correcting energy metabolism, and also assists 5-FU to promote the apoptosis of colon tumor cells by inhibiting their respiration through a CO signaling pathway. High biosafety and therapeutic validity endow the developed suppository with a high potential for clinical translation.", "conclusion": "Mechanistically, H2 generated by CSN reduces the toxicity of 5-FU to normal cells in the intestinal tract by scavenging over-expressed reactive oxygen species and correcting energy metabolism, and also assists 5-FU to promote the apoptosis of colon tumor cells by inhibiting their respiration through a CO signaling pathway. High biosafety and therapeutic validity endow the developed suppository wit" }, { "pmid": "39804806", "year": 2025, "title": "Hydrogen-Rich Saline Combined With Vacuum Sealing Drainage Promotes Wound Healing by Altering Biotin Metabolism.", "title_en": null, "title_de": "Wasserstoffreiche Kochsalzlösung in Kombination mit Vakuumversiegelungsdrainage fördert die Wundheilung durch Veränderung des Biotin-Stoffwechsels", "journal": "Journal of cellular and molecular medicine", "authors": "Kuang et al.", "author_search": "kuang kuang", "doi": "10.1111/jcmm.70292", "doi_url": "https://doi.org/10.1111/jcmm.70292", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39804806/", "url": "https://h2medicine.org/studies/study-kuang-2025-saline-combined-vacuum-sealing/", "methods": [ "saline-iv" ], "indications": [ "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2025 · Kuang et al. — Hydrogen-Rich Saline Combined With Vacuum Sealing Drainage Promotes Wound Healing by Altering Biotin Metabolism", "summary": "Impaired wound healing is a significant clinical burden — particularly in post-surgical or chronic wound settings. This study examined hydrogen-rich saline (HRS) combined with vacuum sealing drainage (VSD) in a rabbit wound model, using untargeted metabolomics to identify the mechanism. The combination outperformed VSD alone in wound closure speed, and pathway analysis pointed to biotin metabolism as the key mechanistic pathway — with downstream effects on mitochondrial function, ATP synthesis, and antioxidant capacity. The study also includes in vitro validation in human keratinocytes. (Journal of Cellular and Molecular Medicine, 2025.)", "assessment": "Mechanistically novel but primarily an animal study. The metabolomics-driven hypothesis (biotin metabolism as H₂ wound healing target) is the main scientific contribution — if replicated, it opens a new mechanistic lane in H₂ biology. However, rabbit full-thickness wound models are not always predictive of human wound healing, particularly in chronic wound contexts. The human keratinocyte data support the mechanism but do not constitute clinical evidence. The study source data classifies this as a human study, but the wound model is animal — the HaCaT cell work is in vitro. Users of this database should note this distinction. No clinical wound data in humans are presented. The combination of HRS + VSD also means H₂ effects cannot be fully decoupled from vacuum therapy effects.", "abstract": "Impaired wound healing affects the life quality of patients and causes a substantial financial burden. Hydrogen-rich medium is reported to have antioxidant and anti-inflammatory effects. However, the role of hydrogen-rich saline (HRS) in cutaneous wound healing remains largely unexplored, especially by metabolomics. Thus, untargeted metabolomics profiling was analysed to study the effects and mechanism of HRS combined with vacuum sealing drainage (VSD) in a rabbit full-thickness wound model. Our results indicated that the combination treatment of HRS and VSD could accelerate wound healing. In vitro experiments further confirmed its effects on HaCaT keratinocytes. We found that 45 metabolites were significantly changed between the VSD + HRS group and the VSD + saline-treated group. Pathway enrichment analysis indicated that biotin metabolism was the potential target pathway. The biochemical interpretation analysis demonstrated that combining HRS and VSD might enhance mitochondrial function, ATP synthesis, and GSH homeostasis by altering biotin metabolism. The detection of representative indicators of oxidative stress supported the critical metabolic pathway analysis as well. In summary, VSD combined with HRS might provide a new strategy to enhance wound healing.", "conclusion": "The detection of representative indicators of oxidative stress supported the critical metabolic pathway analysis as well. In summary, VSD combined with HRS might provide a new strategy to enhance wound healing." }, { "pmid": "39791170", "year": 2025, "title": "Protective Effects of Hydrogen Treatment Against High Glucose-Induced Oxidative Stress and Apoptosis via Inhibition of the AGEs/RAGE/NF-κB Signaling Pathway in Skin Cells.", "title_en": null, "title_de": "Schützende Wirkungen der Wasserstoffbehandlung gegen durch hohe Glukose induzierten oxidativen Stress und Apoptose über die Hemmung des AGEs/RAGE/NF-κB-Signalwegs in Hautzellen.", "journal": "Endocrine, metabolic & immune disorders drug targets", "authors": "Yu et al.", "author_search": "yu yu", "doi": "10.2174/0118715303369584241231141001", "doi_url": "https://doi.org/10.2174/0118715303369584241231141001", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39791170/", "url": "https://h2medicine.org/studies/study-yu-2025-protective-against-high-glucose/", "methods": [ "unspecified" ], "indications": [ "diabetes", "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Yu — Protective Effects of Hydrogen Treatment Against High Glucose-Induced Oxidative Stress and Apoptosis via Inhibition of the AGEs/RAGE/NF-κB Signaling Pathway in Skin Cells.", "summary": "In cell culture, molecular hydrogen protected human skin cells (keratinocytes and fibroblasts) against the oxidative stress and cell death caused by high glucose or advanced glycation end-products (AGEs) — compounds that accumulate in diabetic tissue. H₂ treatment reduced inflammatory markers and inhibited the AGEs/RAGE/NF-κB signalling cascade, which is central to chronic inflammation in diabetic wounds. (Endocrine, Metabolic & Immune Disorders Drug Targets, 2025.)", "assessment": "This is a cell-culture (in-vitro) study — results demonstrate a biologically plausible mechanism for H₂ protection against high-glucose-induced cell damage, but these findings cannot be directly transferred to clinical outcomes in diabetic wound healing. The AGEs/RAGE/NF-κB pathway inhibition is a well-established target, and the data are mechanistically consistent. However, cell viability and cytokine results in a dish do not predict clinical wound-healing outcomes. Animal and human studies are necessary before any clinical conclusions can be drawn.", "abstract": "BACKGROUND: Diabetic wounds are major clinical challenges, often complicated by oxidative stress and free radical generation. Hydrogen (H2), a selective antioxidant, offers potential as a therapeutic agent for chronic diabetic wounds. However, its precise mechanisms remain underexplored. OBJECTIVE: This study aimed to investigate the protective effects of H2 on high glucose-induced oxidative damage and apoptosis in human skin cells. METHODS: HaCaT keratinocytes and HSF fibroblasts were treated with high glucose or AGEs. Cell viability, oxidative stress markers, inflammatory cytokines, and apoptosis were analyzed. AGEs/RAGE/NF-κB signaling was evaluated via Western blot. RESULTS: H2 treatment significantly reduced ROS, MDA, IL-1β, and TNF-α levels, while enhancing SOD and GSH activity. It also inhibited AGEs/RAGE/NF-κB signaling and apoptosis. CONCLUSION: Hydrogen therapy protects against oxidative stress and inflammation induced by high glucose or AGEs, offering potential as an adjunctive treatment for diabetic wound healing.", "conclusion": "Hydrogen therapy protects against oxidative stress and inflammation induced by high glucose or AGEs, offering potential as an adjunctive treatment for diabetic wound healing." }, { "pmid": "39775989", "year": 2025, "title": "Manganese Galvanic Cells Intervene in Tumor Metabolism to Reinforce cGAS-STING Activation for Bidirectional Synergistic Hydrogen-Immunotherapy.", "title_en": null, "title_de": "Mangan-Galvanikzellen greifen in den Tumorstoffwechsel ein, um die cGAS-STING-Aktivierung für eine bidirektionale synergistische Wasserstoff-Immuntherapie zu verstärken.", "journal": "Advanced materials (Deerfield Beach, Fla.)", "authors": "Yang et al.", "author_search": "yang yang", "doi": "10.1002/adma.202414929", "doi_url": "https://doi.org/10.1002/adma.202414929", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39775989/", "url": "https://h2medicine.org/studies/study-yang-2025-manganese-galvanic-cells-intervene/", "methods": [ "inhalation" ], "indications": [ "liver", "cardiovascular", "cancer", "immune-system" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Yang — Manganese Galvanic Cells Intervene in Tumor Metabolism to Reinforce cGAS-STING Activation for Bidirectional Synergistic Hydrogen-Immunotherapy.", "summary": "Manganese galvanic-cell nanostructures (MnG) generate hydrogen and manganese ions inside tumours by reacting with water, simultaneously activating a key innate-immunity pathway (cGAS-STING) and disrupting tumour glucose metabolism. In animal models, MnG combined with immune checkpoint blockade suppressed both injected primary tumours and distant untreated tumours — and showed remarkable efficacy in a rabbit liver tumour model combined with transarterial embolisation. (Advanced Materials, 2025.)", "assessment": "This is a preclinical animal study (mouse + rabbit) — results cannot be directly transferred to humans. The bidirectional cGAS-STING amplification strategy is mechanistically compelling and well-supported by the data presented. The combination with TAE is a clinically realistic administration route for liver tumours. Translational barriers include Mn²⁺ neurotoxicity at higher doses, nanoparticle biodistribution and immune-related toxicity, and the complexity of combining multiple immune-activating agents. No human data exist.", "abstract": "The cGAS-STING pathway is pivotal in initiating antitumor immunity. However, tumor metabolism, particularly glycolysis, negatively regulates the activation of the cGAS-STING pathway. Herein, Mn galvanic cells (MnG) are prepared via liquid-phase exfoliation and in situ galvanic replacement to modulate tumor metabolism, thereby enhancing cGAS-STING activation for bidirectional synergistic H2-immunotherapy. The obtained MnG can be etched by water, enabling efficient and sustained generation of H2 gas and Mn2+. MnG not only activated and amplified the cGAS-STING pathway through the sustained release of Mn2+ but also regulated tumor glucose metabolism to inhibit the expression of three prime repair exonuclease 2 (TREX2), thereby synergistically enhancing the activation of the cGAS-STING pathway. The injection of MnG into tumors resulted in a robust immune response, thereby providing favorable support for antitumor therapy. Consequently, the combination of MnG with immune checkpoint blockade therapy resulted in significant suppression of both primary tumors and distant tumors. Furthermore, the MnG-lipiodol dispersion exhibited remarkable efficacy in combination with transarterial embolization (TAE)-gas-immunotherapy in a rabbit orthotopic liver tumor model. The present study underscores the significance of employing a metal galvanic cell strategy for enhanced immunotherapy, thereby offering a novel approach for rational design of bioactive materials to augment immunotherapeutic effectiveness.", "conclusion": "Furthermore, the MnG-lipiodol dispersion exhibited remarkable efficacy in combination with transarterial embolization (TAE)-gas-immunotherapy in a rabbit orthotopic liver tumor model. The present study underscores the significance of employing a metal galvanic cell strategy for enhanced immunotherapy, thereby offering a novel approach for rational design of bioactive materials to augment immunothe" }, { "pmid": "39740897", "year": 2025, "title": "Molecular Hydrogen as a Potential Adjunctive Therapy to Improve Renal Function and Reduce Fatigue in an Elderly Patient With Chronic Comorbidities: A Case Report.", "title_en": null, "title_de": "Molekularer Wasserstoff als potenzielle adjunktive Therapie zur Verbesserung der Nierenfunktion und Reduktion der Ermüdung bei einem älteren Patienten mit chronischen Komorbiditäten: Ein Fallbericht", "journal": "In vivo (Athens, Greece)", "authors": "Lin et al.", "author_search": "lin lin", "doi": "10.21873/invivo.13862", "doi_url": "https://doi.org/10.21873/invivo.13862", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39740897/", "url": "https://h2medicine.org/studies/study-lin-2025-adjunctive-improve-renal-function/", "methods": [ "unspecified" ], "indications": [ "diabetes", "sports-exercise", "cardiovascular", "kidney-dialysis", "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2025 · Lin et al. — Molecular Hydrogen as a Potential Adjunctive Therapy to Improve Renal Function and Reduce Fatigue in an Elderly Patient With Chronic Comorbidities: A Case Report", "summary": "An 89-year-old woman with coronary artery disease, type 2 diabetes with nephropathy, and SLE — presenting with recurrent wound infection — showed improved renal function and reduced chronic fatigue after adjuvant hydrogen capsule therapy. Serum creatinine declined, the Brief Fatigue Inventory improved significantly, and immunological evaluation revealed immune modulation consistent with therapeutic benefit. (In Vivo, 2025.)", "assessment": "Single case report in an extreme-comorbidity, elderly patient. The creatinine improvement is a meaningful hard endpoint, but without knowing the baseline trajectory of her CKD and whether her wound infection (the primary presentation) had been resolving, natural history confounds are substantial. The wound itself was being treated with antibiotics concurrently. Antibiotic resolution of infection can independently improve renal function (by removing an infectious burden). H₂ may have contributed to renal and fatigue outcomes, but causal attribution is not possible at n=1. The case does, however, represent one of very few reports of H₂ use in an octogenarian/nonagenarian, and the safety profile was excellent.", "abstract": "BACKGROUND/AIM: Hydrogen therapy has demonstrated potential as an antioxidant and anti-inflammatory intervention, particularly in the management of chronic diseases such as chronic kidney disease (CKD) and autoimmune conditions. This case report presents the possible therapeutic benefits of molecular hydrogen capsule treatment in enhancing renal function and alleviating chronic fatigue in an elderly female with coronary artery disease (CAD), type 2 diabetes mellitus (DM) complicated by nephropathy, and systemic lupus erythematosus (SLE). The aim of this study was to investigate the efficacy of adjunctive hydrogen therapy in an elderly patient with multiple chronic comorbidities. CASE REPORT: An 89-year-old female with a history of CAD s/p who had undergone coronary artery bypass grafting (CABG) over 40 years ago, type 2 DM complicated by nephropathy, and SLE was admitted with recurrent cellulitis at the saphenous vein donor site from her previous CABG. Despite antibiotic treatment, wound healing remained limited. In January 2023, the patient initiated adjuvant treatment with molecular hydrogen capsules. Following the introduction of hydrogen therapy, her renal function improved, evidenced by a reduction in serum creatinine levels. Chronic fatigue, assessed using the Taiwan Brief Fatigue Inventory (BFI-T), showed significant improvement. Immunological evaluation revealed a series of changes, suggesting that immune modulation may be the mechanism underlying the observed clinical benefits. CONCLUSION: Hydrogen therapy was associated with improved renal function and a reduced chronic fatigue in this elderly patient with multiple comorbidities, including CAD, DM, and SLE. The case underscores the potential therapeutic role of hydrogen therapy in immune modulation and the management of chronic conditions, suggesting the need for further investigation in clinical settings.", "conclusion": "Hydrogen therapy was associated with improved renal function and a reduced chronic fatigue in this elderly patient with multiple comorbidities, including CAD, DM, and SLE. The case underscores the potential therapeutic role of hydrogen therapy in immune modulation and the management of chronic conditions, suggesting the need for further investigation in clinical settings." }, { "pmid": "39740868", "year": 2025, "title": "Precision Assessment of Anti-NMDA Receptor Encephalitis: A Case Report on Integrating Clinical Course, Immunophenotyping, and Comprehensive Symptomatology in a Pediatric Patient With Adjunctive Hydrogen Therapy.", "title_en": null, "title_de": "Präzise Bewertung der Anti-NMDA-Rezeptor-Enzephalitis: Ein Fallbericht über die Integration von klinischem Verlauf, Immunphänotypisierung und umfassender Symptomatologie bei einem pädiatrischen Patienten mit adjunktiver Wasserstofftherapie", "journal": "In vivo (Athens, Greece)", "authors": "Lin et al.", "author_search": "lin lin", "doi": "10.21873/invivo.13858", "doi_url": "https://doi.org/10.21873/invivo.13858", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39740868/", "url": "https://h2medicine.org/studies/study-lin-2025-precision-anti-nmda-receptor/", "methods": [ "saline-iv" ], "indications": [ "immune-system" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2025 · Lin et al. — Precision Assessment of Anti-NMDA Receptor Encephalitis: A Case Report on Integrating Clinical Course, Immunophenotyping, and Comprehensive Symptomatology in a Pediatric Patient With Adjunctive Hydrogen Therapy", "summary": "Anti-NMDA receptor encephalitis is the most common form of autoimmune encephalitis — and it is notoriously difficult to treat when first-line therapies fail. This case describes a 14-year-old boy who showed poor response to initial immunotherapy but improved significantly after rituximab — with hydrogen therapy added as an adjunct. Immunophenotyping revealed correlations between treatment outcomes and shifts in B cell subsets, PD-1+ cytotoxic T cells, and regulatory T cell subtypes. (In Vivo, 2025.)", "assessment": "Single pediatric case report where rituximab (a well-established second-line agent for anti-NMDAR encephalitis) was the primary therapeutic pivot — and H₂ was an add-on. The patient's improvement is most plausibly attributable to rituximab and natural disease remission, which occurs in many anti-NMDAR encephalitis cases over months. The H₂ contribution cannot be assessed at n=1 alongside rituximab. The intravenous H₂-rich saline delivery method is notable — this is a higher-dose, more controlled route than oral methods. The immunophenotyping analysis is the most scientifically valuable component and could serve as a biomarker template for future interventional studies in autoimmune encephalitis.", "abstract": "BACKGROUND/AIM: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, though rare, is the most common form of autoimmune encephalitis, predominantly affecting young individuals, particularly females. Standard treatments include corticosteroids, intravenous immunoglobulins (IVIG), and plasmapheresis, with rituximab recommended for those unresponsive to first-line therapies. However, reliable biomarkers for clinical assessment remain elusive. This study investigated the efficacy of adjunctive hydrogen therapy in a patient with anti-NMDAR encephalitis. CASE REPORT: This case report describes a 14-year-old boy with anti-NMDAR encephalitis who exhibited poor response to initial treatment, but showed significant improvement with rituximab and adjunctive hydrogen therapy. Immunophenotyping revealed correlations between treatment outcomes and shifts in B cell subsets, PD-1+ cytotoxic T cells, and regulatory T cell subtypes. CONCLUSION: This case underscores the importance of integration traditional clinical assessments with advanced diagnostics such as flow cytometry-based immunophenotyping, and suggests a potential role for hydrogen therapy in modulating immune response in this complex autoimmune condition.", "conclusion": "This case underscores the importance of integration traditional clinical assessments with advanced diagnostics such as flow cytometry-based immunophenotyping, and suggests a potential role for hydrogen therapy in modulating immune response in this complex autoimmune condition." }, { "pmid": "39737874", "year": 2025, "title": "Multifaceted Immunomodulatory Nanocomplexes Target Neutrophilic-ROS Inflammation in Acute Lung Injury.", "title_en": null, "title_de": "Vielseitige immunmodulatorische Nanokomplexe zielen auf neutrophile ROS-Entzündung bei akuter Lungenschädigung ab.", "journal": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)", "authors": "Su et al.", "author_search": "su su", "doi": "10.1002/advs.202411823", "doi_url": "https://doi.org/10.1002/advs.202411823", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39737874/", "url": "https://h2medicine.org/studies/study-su-2025-multifaceted-immunomodulatory-nanocomplexes-target/", "methods": [ "unspecified" ], "indications": [ "respiratory", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Su — Multifaceted Immunomodulatory Nanocomplexes Target Neutrophilic-ROS Inflammation in Acute Lung Injury.", "summary": "A two-pronged nanoparticle system combining a neutrophil-inhibiting drug with hydrogen-releasing silicon nanoparticles significantly reduced lung injury in mouse models of sepsis-induced acute lung injury (ALI). The SiH nanosheets provided sustained hydrogen release to scavenge reactive oxygen species, while the co-delivered drug blocked the key inflammatory neutrophil-signalling cascade, together suppressing both blood and lung immune-cell overactivation. (Advanced Science, 2025.)", "assessment": "This is a preclinical animal study (mouse) — results cannot be directly transferred to humans. The nanocomplex approach addresses a well-defined pathophysiological mechanism in ALI, and the dual-agent design is well-reasoned. However, translating nanoparticle-based therapies into the sepsis-ALI clinical setting is notoriously difficult: rapid disease progression, patient heterogeneity, and nanoparticle biodistribution in inflamed lungs create substantial barriers. No human safety or efficacy data exist for this platform.", "abstract": "The sepsis-induced acute lung injury (ALI) still represents one of the leading causes of death in critically ill patients, underscoring the need for novel therapies. Excessive activation of immune cells and damage of reactive oxygen species (ROS) are the main factors that exacerbate lung injury. Here, the multifaceted immunomodulatory nanocomplexes targeting the proinflammatory neutrophilic activation and ROS damage are established. The S100A8/9 inhibitor, ABR2575, is loaded in the nanocomplexes, which effectively blocks the neutrophils-S100A8/A9- toll-like receptors (TLRS)-Inflammasome signaling in ALI. Synergically, the SiH nanosheets are encapsulated together with ABR2575 into the core of poly(lactic-co-glycolic acid) (PLGA) nanosponges, to achieve sustainable hydrogen release for the alleviation of ROS-induced lung tissue injury, and also promote the M2 polarization of macrophages. This novel combination strategy is proven to significantly suppress the infiltration of neutrophils and pro-inflammatory macrophages into the lungs, decrease the activation of neutrophils and pro-inflammatory monocytes in the blood, facilitate the anti-inflammatory polarization of macrophages and monocytes, and reduce the expression of pro-inflammatory cytokines in both the lung and blood circulation, all of which alleviate the lung injuries in preclinical murine ALI models. The current investigations offer a novel nanomedicine for the treatment of ALI with great potential in clinical invention.", "conclusion": "This novel combination strategy is proven to significantly suppress the infiltration of neutrophils and pro-inflammatory macrophages into the lungs, decrease the activation of neutrophils and pro-inflammatory monocytes in the blood, facilitate the anti-inflammatory polarization of macrophages and monocytes, and reduce the expression of pro-inflammatory cytokines in both the lung and blood circulat" }, { "pmid": "39726077", "year": 2025, "title": "Hydrolysis of 2D Nanosheets Reverses Rheumatoid Arthritis Through Anti-Inflammation and Osteogenesis.", "title_en": null, "title_de": "Hydrolyse von 2D-Nanoblättern kehrt rheumatoide Arthritis durch Entzündungshemmung und Osteogenese um.", "journal": "Advanced materials (Deerfield Beach, Fla.)", "authors": "Ji et al.", "author_search": "ji ji", "doi": "10.1002/adma.202415543", "doi_url": "https://doi.org/10.1002/adma.202415543", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39726077/", "url": "https://h2medicine.org/studies/study-ji-2025-hydrolysis-nanosheets-reverses-rheumatoid/", "methods": [ "inhalation" ], "indications": [ "sports-exercise", "joints-rheumatology", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Ji — Hydrolysis of 2D Nanosheets Reverses Rheumatoid Arthritis Through Anti-Inflammation and Osteogenesis.", "summary": "Two-dimensional calcium disilicide nanoparticles (CSN) hydrolyse in joint fluid to release hydrogen gas, calcium hydroxide, and silica simultaneously — tackling three distinct processes that drive rheumatoid arthritis: oxidative stress, joint acidity, and bone erosion. In arthritic mouse and rabbit models, CSN treatment reversed joint inflammation and stimulated new bone formation significantly better than anti-inflammatory treatment alone. (Advanced Materials, 2025.)", "assessment": "This is a preclinical animal study (mouse + rabbit) — results cannot be directly transferred to humans with rheumatoid arthritis. The multi-mechanistic approach is scientifically well-motivated and delivers promising results across two animal models, going beyond pure anti-inflammation to also address bone repair — a genuine unmet need in RA. Translational challenges include joint pharmacokinetics of nanoparticles, systemic silicon and calcium accumulation, immune reactivity, and the complexity of RA pathophysiology in humans (autoantibodies, T-cell-mediated mechanisms) not fully captured in rodent models. Clinical trials are still many steps away.", "abstract": "Rheumatoid arthritis (RA) is a kind of inflammation homeostasis disorder that dysfunctions the joints. Clinically, medications against RA focus simply on mitigating the focal inflammation, without considering pro-osteogenesis re-modeling of the bone microenvironment. In the present work, 2D layered calcium disilicide nanoparticles (CSNs) are fabricated by facile aqueous exfoliation. The hydrolysis of CSNs produces anti-oxidative H2, alkaline Ca(OH)2, and silica. These moieties play significant roles in anti-oxidation, anti-inflammation, and pro-osteogenesis resulting in considerably better RA therapeutic consequences than anti-inflammation alone. Hydrogen gas is validated to eliminate excessive hydroxyl radicals and regulate macrophage re-polarization; the generated Ca(OH)2 can neutralize the acidic microenvironment and inhibit the osteoclast activity; and, the dissolved Ca2+ can effectively complex with phosphates to mineralize Ca3(PO4)2, promoting the osteogenesis of the focal joint. The multifunctional performances of CSNs are further confirmed in arthritic mouse and rabbit models, providing an advanced and robust therapeutic strategy against RA with high biocompatibility and clinical transformable promises.", "conclusion": "Hydrogen gas is validated to eliminate excessive hydroxyl radicals and regulate macrophage re-polarization; the generated Ca(OH)2 can neutralize the acidic microenvironment and inhibit the osteoclast activity; and, the dissolved Ca2+ can effectively complex with phosphates to mineralize Ca3(PO4)2, promoting the osteogenesis of the focal joint. The multifunctional performances of CSNs are further c" }, { "pmid": "39656877", "year": 2025, "title": "Hydrogen-Generating Magnesium Alloy Seed Strand Sensitizes Solid Tumors to Iodine-125 Brachytherapy.", "title_en": null, "title_de": "Wasserstofferzeugender Magnesiumlegierungs-Seed-Strang sensibilisiert solide Tumoren für die Iod-125-Brachytherapie.", "journal": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)", "authors": "Hu et al.", "author_search": "hu hu", "doi": "10.1002/advs.202412263", "doi_url": "https://doi.org/10.1002/advs.202412263", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39656877/", "url": "https://h2medicine.org/studies/study-hu-2025-generating-magnesium-alloy-seed/", "methods": [ "inhalation" ], "indications": [ "liver", "cancer", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Hu — Hydrogen-Generating Magnesium Alloy Seed Strand Sensitizes Solid Tumors to Iodine-125 Brachytherapy.", "summary": "An AZ31 magnesium-alloy brachytherapy seed strand (AMASS) implanted directly into tumours releases hydrogen gas alongside radioactive iodine-125 radiation, significantly enhancing tumour cell killing compared to radiation alone. In mouse and rabbit tumour models, hydrogen from AMASS degradation disrupted cancer-cell redox balance, reduced ATP production, and induced DNA damage synergistically with ¹²⁵I radiation, with no notable side effects. (Advanced Science, 2025.)", "assessment": "This is a preclinical study (in-vitro + mouse + rabbit) — results cannot be directly transferred to human cancer patients. The combination of an existing clinical technique (¹²⁵I brachytherapy) with local hydrogen generation is a pragmatic and potentially translatable approach, as it builds on an established clinical procedure. Multi-model preclinical evidence (in vitro, mouse, rabbit) is a strength. Remaining open questions: long-term biocompatibility of AZ31 alloy degradation products in human tumours, radiation dosimetry modifications required, and clinical manufacturing standardisation. Human data are absent.", "abstract": "Radioactive iodine-125 (125I) seed implantation, a brachytherapy technique, effectively kills tumor cells via X-rays and gamma rays, serving as an alternative therapeutic option following the failure of frontline treatments for various solid tumors. However, tumor radioresistance limits its efficacy. Hydrogen gas has anticancer properties and can enhance the efficacy of immunotherapy. However, its role in radiotherapy sensitization has rarely been reported. Many current hydrogen delivery methods involve hydrogen-generating nanomaterials, such as magnesium-based nanomaterials. This study introduces an AZ31 magnesium alloy 125I seed strand (termed AMASS) with pH-dependent slow-release hydrogen characteristics and excellent mechanical properties. AMASS can be implanted into tumors via minimally invasive surgery, releasing hydrogen around the 125I seeds. In vitro experiments showed that hydrogen from AMASS degradation significantly inhibited tumor proliferation, increased apoptosis, disrupted redox homeostasis and mitochondrial membrane potential, reduced adenosine triphosphate levels, and induced DNA damage due to 125I radiation. In mouse xenograft and rabbit liver tumor models, hydrogen from AMASS showed superior therapeutic effects compared with 125I seeds alone, with no noticeable side effects. In addition, AMASS has a uniform radiation dose distribution and simple implantation. Therefore, hydrogen from AMASS enhanced 125I seed efficacy, supporting the further promotion and application of 125I seed implantation in cancer therapy.", "conclusion": "In addition, AMASS has a uniform radiation dose distribution and simple implantation. Therefore, hydrogen from AMASS enhanced 125I seed efficacy, supporting the further promotion and application of 125I seed implantation in cancer therapy." }, { "pmid": "39495651", "year": 2025, "title": "Living Therapeutics for Synergistic Hydrogen-Photothermal Cancer Treatment by Photosynthetic Bacteria.", "title_en": null, "title_de": "Lebende Therapeutika für die synergistische photothermische Wasserstoff-Krebsbehandlung durch photosynthetische Bakterien.", "journal": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)", "authors": "Zhang et al.", "author_search": "zhang zhang", "doi": "10.1002/advs.202408807", "doi_url": "https://doi.org/10.1002/advs.202408807", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39495651/", "url": "https://h2medicine.org/studies/study-zhang-2025-living-therapeutics-synergistic-photothermal/", "methods": [ "inhalation" ], "indications": [ "cancer", "fundamentals-safety" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Zhang — Living Therapeutics for Synergistic Hydrogen-Photothermal Cancer Treatment by Photosynthetic Bacteria.", "summary": "Living photosynthetic bacteria (Rhodobacter sphaeroides) were used as a self-powered, targeted platform that simultaneously generates hydrogen gas and converts near-infrared light into heat inside tumours. In animal experiments, this dual hydrogen-plus-photothermal approach killed tumour cells more effectively than either therapy alone, while sparing surrounding healthy tissue. (Advanced Science, 2025.)", "assessment": "This is a preclinical animal study — results cannot be directly transferred to humans. The living-therapeutic concept is inventive and leverages natural biology elegantly, but the translation challenges are considerable: bacterial immunogenicity, infection risk, consistency of H₂ production in vivo, light penetration depth for NIR photothermal therapy in deep tumours, and the complex regulatory landscape for live microbial therapeutics. No human data exist for this approach, and clinical translation is still at a very early conceptual stage.", "abstract": "Hydrogen gas (H2) therapy, recognized for its inherent biosafety, holds significant promise as an anti-cancer strategy. However, the efficacy of H2 treatment modalities is compromised by their reliance on systemic gas administration or chemical reactions generation, which suffers from low efficiency, poor targeting, and suboptimal utilization. In this study, living therapeutics are employed using photosynthetic bacteria Rhodobacter sphaeroides for in situ H2 production combined with near-infrared (NIR) mediated photothermal therapy. Living R. sphaeroides exhibits strong absorption in the NIR spectrum, effectively converting light energy into thermal energy while concurrently generating H2. This dual functionality facilitates the targeted induction of tumor cell death and substantially reduces collateral damage to adjacent normal tissues. The findings reveal that integrating hydrogen therapy with photothermal effects, mediated through photosynthetic bacteria, provides a robust, dual-modality approach that enhances the overall efficacy of tumor treatments. This living therapeutic strategy not only leverages the therapeutic potential of both hydrogen and photothermal therapeutic modalities but also protects healthy tissues, marking a significant advancement in cancer therapy techniques.", "conclusion": "The findings reveal that integrating hydrogen therapy with photothermal effects, mediated through photosynthetic bacteria, provides a robust, dual-modality approach that enhances the overall efficacy of tumor treatments. This living therapeutic strategy not only leverages the therapeutic potential of both hydrogen and photothermal therapeutic modalities but also protects healthy tissues, marking a" }, { "pmid": "39426122", "year": 2025, "title": "Engineering probiotic biohydrogen micro-factories to initiate reductive stress for boosting tumor vulnerability.", "title_en": null, "title_de": "Entwicklung probiotischer Biowasserstoff-Mikrofabriken zur Auslösung von reduktivem Stress zur Verstärkung der Tumorvulnerabilität.", "journal": "Biomaterials", "authors": "Jiang et al.", "author_search": "jiang jiang", "doi": "10.1016/j.biomaterials.2024.122892", "doi_url": "https://doi.org/10.1016/j.biomaterials.2024.122892", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39426122/", "url": "https://h2medicine.org/studies/study-jiang-2025-engineering-probiotic-biohydrogen-micro/", "methods": [ "unspecified" ], "indications": [ "liver", "cancer", "respiratory", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Jiang — Engineering probiotic biohydrogen micro-factories to initiate reductive stress for boosting tumor vulnerability.", "summary": "Probiotic bacteria (Enterobacter aerogenes) engineered into gel-based microcapsules produced continuous hydrogen inside tumours, inducing a state of „reductive stress“ — the opposite of oxidative stress — that disrupted cancer-cell metabolism and suppressed tumour growth. In mouse models of breast, melanoma, and liver cancer, the hydrogen-producing microcapsules also enhanced the effect of chemotherapy and reduced lung metastasis. (Biomaterials, 2025.)", "assessment": "This is a preclinical animal study — results cannot be directly transferred to humans. The reductive-stress concept is novel and mechanistically well-supported by this data. Showing efficacy across eight tumour cell lines and three animal tumour models (breast, melanoma, liver) is a meaningful breadth of evidence for a single preclinical study. However, translational barriers are real: bacterial safety in cancer patients (who are often immunocompromised), long-term fate of microcapsules, and the question of whether reductive stress from H₂ is sufficiently selective for cancer vs. normal cells in vivo remain unresolved. No human data exist.", "abstract": "Disruption of redox homeostasis profoundly affects cellular metabolism and activities. While oxidative stress is extensively studied in cancer therapies, research on reductive stress remains in its infancy. Molecular hydrogen (H2), a well-known antioxidant, holds significant potential to induce reductive stress due to its strong antioxidative properties, making it a promising candidate for cancer therapy. However, it remains a major challenge to develop a sustainable H2 delivery system in vivo. Herein, we designed a micro-factory by engineering a gel-based microcapsule that encapsulates Enterobacter aerogenes, a.k.a. probiotic biohydrogen microcapsules (PBMCs), enabling the sustained H2 generation within tumor microenvironment. Notably, PBMCs effectively suppressed the proliferation of eight tumor cell lines as well as drug-resistant cancer cells. The prolonged H2 release from PBMCs induced reductive stress, as evidenced by a significant increase in the GSH/GSSG ratio in 4T1 cells. Moreover, PBMCs displayed significant antitumor effects in breast, melanoma and liver cancer models. The inhibition of PI3K-AKT pathway and the activation of MAPK pathway were identified as key mechanisms responsible for inducing tumor cell cycle arrest and apoptosis. The PBMCs also exhibited synergistic effects in combination with chemotherapeutics, resulting in robust inhibitions of preinvasive carcinoma growth and commonly associated pulmonary metastasis. Overall, our study introduces an innovative strategy to manipulate reductive stress in the tumor microenvironment through in situ H2 generation, thereby enhancing tumor vulnerability.", "conclusion": "The PBMCs also exhibited synergistic effects in combination with chemotherapeutics, resulting in robust inhibitions of preinvasive carcinoma growth and commonly associated pulmonary metastasis. Overall, our study introduces an innovative strategy to manipulate reductive stress in the tumor microenvironment through in situ H2 generation, thereby enhancing tumor vulnerability." }, { "pmid": "39190941", "year": 2025, "title": "Mitochondrial 'Birth-Death' coordinator: An intelligent hydrogen nanogenerator to enhance intervertebral disc regeneration.", "title_en": null, "title_de": "Mitochondrialer ‚Geburt-Tod'-Koordinator: Ein intelligenter Wasserstoff-Nanogenerator zur Verstärkung der Bandscheibenregeneration", "journal": "Biomaterials", "authors": "Ji et al.", "author_search": "ji ji", "doi": "10.1016/j.biomaterials.2024.122764", "doi_url": "https://doi.org/10.1016/j.biomaterials.2024.122764", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39190941/", "url": "https://h2medicine.org/studies/study-ji-2025-mitochondrial-birth-death-coordinator/", "methods": [ "inhalation" ], "indications": [ "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Ji — Mitochondrial 'Birth-Death' Coordinator: An Intelligent Hydrogen Nanogenerator to Enhance Intervertebral Disc Regeneration", "summary": "Researchers developed a smart nanoparticle (Fe@HP-OD) that releases molecular hydrogen (H₂) precisely inside degenerated intervertebral discs (IVDs) in response to the local microenvironment. In animal and cell models, this nanogenerator reduced oxidative stress, restored nucleus pulposus cell function, and promoted disc regeneration by coordinating two opposing mitochondrial processes — biogenesis (‚Birth') and mitophagy (‚Death'). This study is preclinical; its findings do not yet apply to humans.", "assessment": "This is a preclinical proof-of-concept study (cell + rodent models) — not a human trial. The mechanistic framing of mitochondrial ‚Birth-Death' coordination via H₂ is novel and scientifically interesting, and the stimulus-responsive nanogenerator design is sophisticated. However, engineering such nanoparticles for safe spinal use in humans involves enormous hurdles: biocompatibility, regulatory approval, delivery route, and long-term safety. Conclusions must not be extrapolated to humans. The study contributes to mechanistic understanding; clinical relevance is speculative at this stage.", "abstract": "Currently, mitochondrial dysfunction caused by oxidative stress is a growing concern in degenerative diseases, notably intervertebral disc degeneration (IVDD). Dysregulation of the balance of mitochondrial quality control (MQC) has been considered the key contributor, while it's still challenging to effectively harmonize different MQC components in a simple and biologically safe way. Hydrogen gas (H2) is a promising mitochondrial therapeutic molecule due to its bio-reductivity and diffusibility across cellular membranes, yet its relationship with MQC regulation remains unknown. Herein, we propose a mitochondrial 'Birth-Death' coordinator achieved by an intelligent hydrogen nanogenerator (Fe@HP-OD), which can sustainably release H2 in response to the unique microenvironment in degenerated IVDs. Both in vitro and in vivo results prove alleviation of cellular oxidative stress and restoration of nucleus pulposus cells function, thereby facilitating successful IVD regeneration. Significantly, this study for the first time proposes the mitochondrial 'Birth-Death' coordination mechanism: 1) attenuation of overactivated mitochondrial 'Death' process (UPRmt and unselective mitophagy); and 2) activation of Adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling pathway for mitochondrial 'Birth-Death' balance (mitochondrial biogenesis and controlled mitophagy). These pioneering findings can fill in the gaps in molecular mechanisms for H2 regulation on MQC homeostasis, and pave the way for future strategies towards restoring equilibrium of MQC system against degenerative diseases.", "conclusion": "Significantly, this study for the first time proposes the mitochondrial 'Birth-Death' coordination mechanism: 1) attenuation of overactivated mitochondrial 'Death' process (UPRmt and unselective mitophagy); and 2) activation of Adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling pathway for mitochondrial 'Birth-Death' balance (mitochondrial biogenesis and controlled mitophagy). Th" }, { "pmid": "38634423", "year": 2025, "title": "Effect of hydrogen-rich saline on melanopsin after acute blue light-induced retinal damage in rats", "title_en": null, "title_de": "Wirkung von wasserstoffreicher Kochsalzlösung auf Melanopsin nach akutem blaulichtinduziertem Netzhautschaden bei Ratten", "journal": "Photochemistry and Photobiology", "authors": "Wang et al.", "author_search": "wang wang", "doi": "10.1111/php.13952", "doi_url": "https://doi.org/10.1111/php.13952", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38634423/", "url": "https://h2medicine.org/studies/study-wang-2025-hydrogen-rich-saline-melanopsin-blue-light-retina/", "methods": [ "saline-iv" ], "indications": [ "eye", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Wang — Effect of hydrogen-rich saline on melanopsin after acute blue light-induced retinal damage in rats", "summary": "Hydrogen protects the retina from blue light: In rats with blue-light-induced retinal damage, hydrogen-rich saline (HRS) accelerated recovery — with markedly more melanopsin and more functional light-sensitive ganglion cells within two weeks. (Photochemistry and Photobiology, 2025.)", "assessment": "A clean mechanistic study on an everyday stimulus (blue light) on a defined cell type of the retina. The strength is that the authors carry along the spontaneous self-recovery as a comparison — so the HRS benefit is the acceleration versus the natural course, not a restoration from nothing. Notable for translation to humans: the delivery form here is H₂-rich saline (intraperitoneal/injectable in the animal model), not orally administered H₂ water. Limitation, stated honestly: purely preclinical (rat), abstract without hard numbers/p-values, narrow indication window; no statement about vision improvement in humans.", "abstract": "Excessive exposure to blue light can cause retinal damage. Hydrogen-rich saline (HRS), one of the hydrogen therapies, has been demonstrated to be effective in eye photodamage, but the effect on the expression of melanopsin in intrinsically photosensitive retinal ganglion cells (ipRGCs) is unknown. In this study, we used a rat model of light-induced retinal injury to observe the expression of melanopsin after HRS treatment and to determine the effect of HRS on retinal ganglion cell protection. Adult SD rats were exposed to blue light (48 h) and treated with HRS for 0, 3, 7, and 14 days. Real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB) were performed to find the expression of genes and proteins, respectively. The function of retinal ipRGCs was measured by pattern-evoked electroretinography (pERG). The number and morphological changes of melanopsin-positive ganglion cells in the retina were observed by immunofluorescence (IF). Acute blue light exposure caused a decrease in ipRGC function, decreased expression of melanopsin protein and the melanopsin-positive RGCs, and diminished immunoreactivity in dendrites. However, over time, melanopsin showed a tendency to self-recovery, with an increase in melanopsin protein expression and the number of melanopsin-positive RGCs, with incomplete recovery of function within two weeks. HRS treatment accelerated the recovery process, with a significant increase in melanopsin expression and the number of melanopsin-positive RGCs, and an improvement in the pERG waveform within two weeks.", "conclusion": "However, over time, melanopsin showed a tendency to self-recovery, with an increase in melanopsin protein expression and the number of melanopsin-positive RGCs, with incomplete recovery of function within two weeks. HRS treatment accelerated the recovery process, with a significant increase in melanopsin expression and the number of melanopsin-positive RGCs, and an improvement in the pERG waveform" }, { "pmid": "40411985", "year": 2025, "title": "Hydrogen activates ACOD1-itaconate pathway to ameliorate steroid-associated osteonecrosis", "title_en": null, "title_de": "Wasserstoff aktiviert den ACOD1-Itaconat-Signalweg zur Linderung steroidassoziierter Osteonekrose", "journal": "Biomaterials", "authors": "An et al.", "author_search": "an an", "doi": "10.1016/j.biomaterials.2025.123428", "doi_url": "https://doi.org/10.1016/j.biomaterials.2025.123428", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40411985/", "url": "https://h2medicine.org/studies/study-an-2025-acod1-itaconate-steroid-osteonecrosis/", "methods": [ "drinking-hrw" ], "indications": [ "joints-rheumatology", "oxidative-stress", "fundamentals" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · An — Hydrogen activates ACOD1-itaconate pathway to ameliorate steroid-associated osteonecrosis", "summary": "Hydrogen-rich water (HRW) protects bone from cortisone damage: In the mouse model of steroid-induced bone necrosis, H₂ reduced the death of bone cells, improved bone structure and blood perfusion — via activation of the anti-inflammatory ACOD1-itaconate metabolic pathway. (Biomaterials, 2025.)", "assessment": "A mechanistically strong piece of work from the high-ranking journal Biomaterials: it links drinkable H₂ water with a precise molecular protective pathway (ACOD1/itaconate) and at the same time shows hard endpoints (bone structure, blood perfusion, blood lipids). Notable because it examines orally administered HRW — here in an indication field beyond the usual antioxidant mechanistic picture. Limitation, stated honestly: purely preclinical (mouse), model with artificially induced necrosis; no transferability to patients without clinical studies. Statements like „prevents bone necrosis“ apply explicitly only to the mouse model.", "abstract": "Steroid-associated osteonecrosis (SAON) remains a challenging clinical condition as there are few effective preventive measures. This study investigates the effects of hydrogen (H2) administrated via saturated hydrogen-rich water (HRW) in mice received high dose of glucocorticoids (for inducing SAON model). Here we find that HRW treatment significantly reduces osteocyte apoptosis, improves deteriorated trabecular architecture, increases osteoblast numbers and the bone formation, while decreases osteoclast numbers and the bone resorption. Additionally, HRW-treated mice exhibit improved serum lipid profiles, including decreased levels of low-density lipoprotein (LDL), triglycerides (TG), and total cholesterol (T-CHO), as well as reduced lipid accumulation. HRW treatment also enhances blood perfusion and increases formation of type H vessels in SAON mice. We further demonstrate that HRW shifts the polarization of macrophages from M1 to M2 phenotype and suppresses inflammatory marker TNF-α. RNA sequencing data and subsequent validation reveal that HRW upregulates ACOD1 mRNA and protein levels in bone tissues. The protective effects of HRW are mimicked by supplementation with the itaconate derivative dimethyl itaconate in a dose-dependent manner, highlighting the importance of the ACOD1-itaconate pathway in the prevention of SAON by HRW. These findings indicate that HRW ameliorates SAON by modulating the ACOD1-itaconate pathway, presenting a novel avenue for the cost-effective prevention of osteonecrosis.", "conclusion": "The protective effects of HRW are mimicked by supplementation with the itaconate derivative dimethyl itaconate in a dose-dependent manner, highlighting the importance of the ACOD1-itaconate pathway in the prevention of SAON by HRW. These findings indicate that HRW ameliorates SAON by modulating the ACOD1-itaconate pathway, presenting a novel avenue for the cost-effective prevention of osteonecrosi" }, { "pmid": "40705191", "year": 2025, "title": "Molecular hydrogen attenuates cisplatin-induced nephrotoxicity by modulating β-hydroxybutyrate metabolism", "title_en": null, "title_de": "Molekularer Wasserstoff mildert die durch Cisplatin ausgelöste Nierentoxizität durch Modulation des β-Hydroxybutyrat-Stoffwechsels", "journal": "Molecular Biology Reports", "authors": "Tian et al.", "author_search": "tian tian", "doi": "10.1007/s11033-025-10845-0", "doi_url": "https://doi.org/10.1007/s11033-025-10845-0", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/40705191/", "url": "https://h2medicine.org/studies/study-tian-2025-cisplatin-nephrotoxicity-beta-hydroxybutyrate/", "methods": [ "inhalation" ], "indications": [ "kidney-dialysis", "cancer", "oxidative-stress", "metabolic" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2025 · Tian — Molecular hydrogen attenuates cisplatin-induced nephrotoxicity by modulating β-hydroxybutyrate metabolism", "summary": "Hydrogen (H₂) protects the kidney against chemotherapy damage: In a mouse model, inhaled H₂ markedly mitigated the kidney injury caused by the cancer drug cisplatin — via a newly discovered metabolic pathway: H₂ boosts the formation of the ketone body β-hydroxybutyrate, thereby dampening inflammation and cell death in kidney tissue. (Molecular Biology Reports, 2025.)", "assessment": "The study is relevant for H₂ research because it goes beyond the known radical-scavenger effect and points to a concrete metabolic pathway (ketone bodies/β-HOB) — that is mechanistically novel and well documented. It fits into the line of tissue-protection studies, but is not evidence for consuming H₂ water: H₂ was delivered here by inhalation, not via drinking water. Limitations, stated honestly: purely preclinical (mouse + cells), no human data; the transfer to patients is open; and the topic of „protection against chemo side effects“ is medically sensitive — no healing promises may be derived from it. Furthermore: the dataset listed a DOI that does not match the journal/year (Hindawi prefix + an embedded year 2019 for a 2025 paper) — it was omitted as probably incorrect; the canonical reference is the PubMed link.", "abstract": "Nephrotoxicity is a common adverse effect of many chemotherapeutic agents and represents a major dose-limiting factor in cancer treatment. Therefore, developing effective renoprotective strategies is urgently needed. Molecular hydrogen (H2) has emerged as a therapeutic agent with potent antioxidant and anti-inflammatory properties, selectively scavenging hydroxyl radicals and alleviating tissue injury. However, the protective effects and underlying mechanisms of H2 in chemotherapy-induced acute kidney injury (AKI) remain poorly understood. A cisplatin-induced AKI mouse model was established with or without H₂ administration. Kidney injury biomarkers were evaluated, and levels of inflammation and apoptosis were assessed using TUNEL staining, ELISA, and immunohistochemistry. To investigate the underlying mechanisms, RNA sequencing was performed, followed by heatmap, Venn diagram, and volcano plot analyses to identify differentially expressed genes. KEGG pathway enrichment analysis was used to explore metabolic alterations upon H2 treatment in cisplatin-induced nephrotoxicity. Subsequently, metabolic alterations were validated through a series of in vivo and in vitro experiments, including ELISA, flow cytometry, qRT-PCR, western blotting, and immunohistochemistry. H2 inhalation significantly attenuated cisplatin-induced kidney injury by reducing inflammation and apoptosis in renal tissue. Transcriptomic analysis revealed that H2 upregulated the ketone body metabolic pathway, particularly enhancing β-hydroxybutyrate (β-HOB) synthesis via increased expression of the ketogenic enzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2). Functional assays confirmed that H2-mediated upregulation of HMGCS2 and β-HOB contributed to its renoprotective effects. Molecular hydrogen confers protection against cisplatin-induced nephrotoxicity by modulating β-HOB metabolism through upregulation of HMGCS2, thereby suppressing renal inflammation and apoptosis. These findings provide new insights into the metabolic mechanism underlying H2's tissue-protective effects and offer a theoretical foundation for its potential clinical application in mitigating chemotherapy-induced kidney injury.", "conclusion": "Molecular hydrogen confers protection against cisplatin-induced nephrotoxicity by modulating β-HOB metabolism through upregulation of HMGCS2, thereby suppressing renal inflammation and apoptosis. These findings provide new insights into the metabolic mechanism underlying H2's tissue-protective effects and offer a theoretical foundation for its potential clinical application in mitigating chemother" }, { "pmid": "38256045", "year": 2024, "title": "Hydrogen Water: Extra Healthy or a Hoax?-A Systematic Review", "title_en": null, "title_de": "Wasserstoffwasser: extra gesund oder Schwindel? — Eine systematische Übersicht", "journal": "International Journal of Molecular Sciences", "authors": "Dhillon et al.", "author_search": "dhillon dhillon", "doi": "10.3390/ijms25020973", "doi_url": "https://doi.org/10.3390/ijms25020973", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38256045/", "url": "https://h2medicine.org/studies/study-dhillon-2024-hydrogen-water-hoax-systematic-review/", "methods": [ "drinking-hrw" ], "indications": [ "fundamentals", "oxidative-stress", "sports-exercise", "liver", "cardiovascular", "neurology", "respiratory", "skin-aging" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2024 · Dhillon — Hydrogen Water: Extra Healthy or a Hoax?—A Systematic Review", "summary": "Hydrogen-rich water (HRW) — healthy or hype? A systematic review of 25 studies concludes: the antioxidant and anti-inflammatory effects are „encouraging“ in early clinical studies, but not yet conclusive — larger studies are needed. (International Journal of Molecular Sciences, 2024 — an honest stocktaking.)", "assessment": "This is one of the most useful sources there is, because it builds credibility instead of hyping. A systematic review in a peer-reviewed journal that looks at hydrogen water across eight application fields and arrives at a nuanced „yes, but“ is exactly the engineering-honest tone we want. It serves as an umbrella reference for several product arguments (sport, liver, heart, mood). Limitations, stated honestly: it is a review, not its own proof of efficacy — its weight depends entirely on the quality of the 25 included studies, many of which are small and partly open-label. The authors themselves call for larger, methodologically more rigorous studies. Anyone citing this source should always include the „further research is needed“ sentence.", "abstract": "Hydrogen-rich water (HRW) has emerged as a novel approach in the field of health and wellness. It is believed to have therapeutic antioxidant properties that can neutralize harmful free radicals in the human body. It has also been shown to be beneficial in mitigating oxidative stress-induced damage through its anti-inflammatory and anti-apoptotic pathways. We aim to conduct a systematic review to evaluate the potential benefits of hydrogen-rich water. The review protocol was uploaded on PROSPERO. After the initial search criteria, the articles were reviewed by two blinded investigators, and a total of 25 articles were included in the systematic review. The potential benefits of hydrogen-rich water on various aspects of health, including exercise capacity, physical endurance, liver function, cardiovascular disease, mental health, COVID-19, oxidative stress, and anti-aging research, are a subject of growing interest and ongoing research. Although preliminary results in clinical trials and studies are encouraging, further research with larger sample sizes and rigorous methodologies is needed to substantiate these findings. Current research needs to fully explain the mechanisms behind the potential benefits of hydrogen-rich water. Continued scientific exploration will provide valuable insights into the potential of hydrogen-rich water as an adjunctive therapeutic approach in the future.", "conclusion": "Current research needs to fully explain the mechanisms behind the potential benefits of hydrogen-rich water. Continued scientific exploration will provide valuable insights into the potential of hydrogen-rich water as an adjunctive therapeutic approach in the future." }, { "pmid": "39808170", "year": 2024, "title": "New possibilities of the prevention and treatment of cardiovascular pathologies. the potential of molecular hydrogen in the reduction of oxidative stress and its consequences.", "title_en": null, "title_de": "Neue Möglichkeiten der Prävention und Behandlung kardiovaskulärer Pathologien: Das Potenzial von molekularem Wasserstoff bei der Reduzierung von oxidativem Stress", "journal": "Physiological research", "authors": "Slezák et al.", "author_search": "slezák slezák", "doi": "10.33549/physiolres.935491", "doi_url": "https://doi.org/10.33549/physiolres.935491", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39808170/", "url": "https://h2medicine.org/studies/study-slezak-2024-possibilities-prevention-cardiovascular-pathologies/", "methods": [ "unspecified" ], "indications": [ "metabolic", "sports-exercise", "neurology", "cardiovascular", "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2024 · Slezák — New Possibilities of the Prevention and Treatment of Cardiovascular Pathologies: The Potential of Molecular Hydrogen in the Reduction of Oxidative Stress", "summary": "This review examines molecular hydrogen (H₂) as a selective antioxidant with particular promise for cardiovascular disease, where oxidative stress plays a defining role. Unlike conventional antioxidants — which have largely failed in clinical trials — H₂ neutralises only the most damaging reactive oxygen species (·OH) while leaving beneficial ROS for normal cell signalling intact. The authors summarise the current mechanistic and clinical evidence base. This is a literature review, not a new experimental study.", "assessment": "This is a narrative review — it synthesises existing literature rather than generating new experimental data. The selective-antioxidant hypothesis for H₂ is well-supported mechanistically and aligns with a broad body of preclinical work. However, the review does not provide pooled effect sizes or a systematic quality assessment of the included studies, which limits the strength of its conclusions. The field still needs large, well-powered randomised controlled trials, especially in cardiovascular populations. The authors' enthusiasm for H₂ should be read in the context of these limitations.", "abstract": "Disproportion between reactive oxygen species (ROS) production and the body's antioxidant system can cause oxidative stress, which is considered a common denominator in various pathological conditions, including cardiovascular diseases, aging, and cognitive disorders. The generation of free radicals, which occurs through partial reduction of oxygen, can quickly overwhelm the endogenous antioxidant system capacity of the cell. This causes lipid, protein, DNA and RNA damage, inflammation, and overall cell degeneration, which can be mitigated by various antioxidants. However, their use in human medicine did not bring the expected effect. Molecular hydrogen (H2), due to its unique physical and chemical properties, provides a number of benefits for alleviating oxidative stress. H2 is superior to conventional antioxidants as it can selectively reduce (.)OH radicals while preserving important ROS that are otherwise used for normal cell signaling. Key words Oxidative stress, Cardiovascular diseases, Molecular hydrogen, ROS, Inflammation.", "conclusion": "H2 is superior to conventional antioxidants as it can selectively reduce (.)OH radicals while preserving important ROS that are otherwise used for normal cell signaling. Key words Oxidative stress, Cardiovascular diseases, Molecular hydrogen, ROS, Inflammation." }, { "pmid": "39487838", "year": 2024, "title": "Perspective targeted diagnosis and therapy of mitochondrial bioenergetics across different diagnoses.", "title_en": null, "title_de": "Perspektivische gezielte Diagnose und Therapie der mitochondrialen Bioenergetik bei verschiedenen Diagnosen", "journal": "Bratislavske lekarske listy", "authors": "Glevicka et al.", "author_search": "glevicka glevicka", "doi": "10.4149/bll_2024_105", "doi_url": "https://doi.org/10.4149/bll_2024_105", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39487838/", "url": "https://h2medicine.org/studies/study-glevicka-2024-perspective-targeted-diagnosis-mitochondrial/", "methods": [ "drinking-hrw" ], "indications": [ "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2024 · Glevicka — Perspective Targeted Diagnosis and Therapy of Mitochondrial Bioenergetics Across Different Diagnoses", "summary": "This review explores innovative ways to diagnose and treat mitochondrial dysfunction — a root cause shared across many diseases — using high-resolution respirometry (HRR) of blood platelets as a minimally invasive diagnostic tool. Among the therapeutic strategies discussed, molecular hydrogen is listed alongside coenzyme Q10, mitochondrial transplantation, and platelet-rich plasma as an approach to reduce oxidative stress and improve mitochondrial function. This is a literature review; no new experimental data are presented.", "assessment": "This is a review article surveying diagnostic and therapeutic approaches to mitochondrial dysfunction. H₂ is one among several listed strategies and is not systematically evaluated here in isolation. The paper adds useful clinical context — framing H₂ as part of a broader mitochondrial-medicine toolkit — but does not provide independent evidence for H₂ efficacy. Readers seeking quantitative evidence for H₂ specifically should consult dedicated H₂ reviews or clinical trials.", "abstract": "Important metabolic variables that lead to the development of many diseases, including \"mitochondrial diseases,\" include increased oxidative stress and mitochondrial malfunction. Given that the clinical picture and metabolic alterations in individuals suspected of having mitochondrial illnesses lack distinct characteristics, the development of sensitive and specific diagnostic techniques to detect alterations in mitochondrial bioenergetics is imperative. High-resolution respirometry (HRR), is a minimally invasive technique that enables the analysis of mitochondrial function in platelets taken from peripheral blood. This method allows for the detection of even the most subtle changes prior to disease development. HRR can identify minute variations in mitochondrial bioenergetics. Determining mitochondrial function and endogenous levels of CoQ10 in platelets can aid in the early detection of pathobiochemical changes in mitochondria and assessment of treatment efficacy. When combined with the measurement of endogenous coenzyme Q10 levels, HRR may be an effective approach for early identification of compromised mitochondrial function along with monitoring the therapeutic outcomes. Supplementing with coenzyme Q10, applying molecular hydrogen, transplanting mitochondria, and applying platelet-rich plasma (PRP) are some of the therapeutic strategies utilized to enhance mitochondrial function and reduce oxidative stress (Tab. 1, Fig. 1, Ref. 62). Text in PDF www.elis.sk Keywords: mitochondrial dysfunction, oxidative stress, mitochondrial bioenergetics, high-resolution respirometry, therapeutic approaches.", "conclusion": "62). Text in PDF www.elis.sk Keywords: mitochondrial dysfunction, oxidative stress, mitochondrial bioenergetics, high-resolution respirometry, therapeutic approaches." }, { "pmid": "39166484", "year": 2024, "title": "The Landscape of Smart Biomaterial-Based Hydrogen Therapy.", "title_en": null, "title_de": "Die Landschaft der auf intelligenten Biomaterialien basierenden Wasserstofftherapie", "journal": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)", "authors": "Xu et al.", "author_search": "xu xu", "doi": "10.1002/advs.202401310", "doi_url": "https://doi.org/10.1002/advs.202401310", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39166484/", "url": "https://h2medicine.org/studies/study-xu-2024-landscape-smart-biomaterial/", "methods": [ "inhalation" ], "indications": [ "metabolic", "liver", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2024 · Xu — The Landscape of Smart Biomaterial-Based Hydrogen Therapy", "summary": "This comprehensive review maps the rapidly evolving field of biomaterial-based H₂ delivery systems — engineered materials that can carry, target, and release molecular hydrogen precisely where disease processes occur. The authors explain how these ‚smart' biomaterials overcome the key limitation of conventional H₂ therapy (rapid dilution, no tissue targeting) by responding to disease-specific stimuli such as ROS, acidic pH, or near-infrared light. This is a literature review, not a new experimental study.", "assessment": "This is a comprehensive narrative review of an emerging bioengineering field. It does not generate new clinical evidence but is valuable for understanding where the frontiers of H₂ delivery technology are. The stimulus-responsive biomaterial approach addresses a genuine limitation of conventional H₂ therapy. However, nearly all described systems remain at the preclinical stage; clinical translation faces standard nanoparticle hurdles (toxicity, manufacturability, regulatory pathway). Readers should not interpret this review as evidence that biomaterial-based H₂ therapy is clinically proven.", "abstract": "Hydrogen (H2) therapy is an emerging, novel, and safe therapeutic modality that uses molecular hydrogen for effective treatment. However, the impact of H2 therapy is limited because hydrogen molecules predominantly depend on the systemic administration of H2 gas, which cannot accumulate at the lesion site with high concentration, thus leading to limited targeting and utilization. Biomaterials are developed to specifically deliver H2 and control its release. In this review, the development process, stimuli-responsive release strategies, and potential therapeutic mechanisms of biomaterial-based H2 therapy are summarized. H2 therapy. Specifically, the produced H2 from biomaterials not only can scavenge free radicals, such as reactive oxygen species (ROS) and lipid peroxidation (LPO), but also can inhibit the danger factors of initiating diseases, including pro-inflammatory cytokines, adenosine triphosphate (ATP), and heat shock protein (HSP). In addition, the released H2 can further act as signal molecules to regulate key pathways for disease treatment. The current opportunities and challenges of H2-based therapy are discussed, and the future research directions of biomaterial-based H2 therapy for clinical applications are emphasized.", "conclusion": "In addition, the released H2 can further act as signal molecules to regulate key pathways for disease treatment. The current opportunities and challenges of H2-based therapy are discussed, and the future research directions of biomaterial-based H2 therapy for clinical applications are emphasized." }, { "pmid": "39111696", "year": 2024, "title": "Evolution of therapeutic strategy based on oxidant-antioxidant balance for fuchs endothelial corneal dystrophy.", "title_en": null, "title_de": "Entwicklung therapeutischer Strategien auf Basis des Oxidantien-Antioxidantien-Gleichgewichts bei der Fuchs-Endotheldystrophie der Hornhaut", "journal": "The ocular surface", "authors": "Wu et al.", "author_search": "wu wu", "doi": "10.1016/j.jtos.2024.08.003", "doi_url": "https://doi.org/10.1016/j.jtos.2024.08.003", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39111696/", "url": "https://h2medicine.org/studies/study-wu-2024-evolution-therapeutic-strategy-oxidant/", "methods": [ "unspecified" ], "indications": [ "cardiovascular", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2024 · Wu — Evolution of Therapeutic Strategy Based on Oxidant-Antioxidant Balance for Fuchs Endothelial Corneal Dystrophy", "summary": "Fuchs endothelial corneal dystrophy (FECD) — the most common primary corneal endothelial disease worldwide — is closely linked to oxidative stress and antioxidant imbalance. This review outlines therapeutic strategies aimed at restoring this balance, including gene therapy, small molecules, biologics, and non-pharmacological approaches such as hydrogen therapy and near-infrared light. Given the limited availability of donor corneas, non-surgical treatments are urgently needed. This is a literature review, not a clinical trial.", "assessment": "This is a narrative review of FECD therapeutics. H₂ appears as one item in a broader treatment catalogue and is not evaluated in depth with clinical data. The paper usefully contextualises the oxidative-stress basis of FECD and the unmet need for non-surgical options. For evidence specific to H₂ in FECD or corneal disease, dedicated studies or trials would need to be consulted — this review does not provide them.", "abstract": "Fuchs endothelial corneal dystrophy (FECD) stands as the most prevalent primary corneal endothelial dystrophy worldwide, posing a significant risk to corneal homeostasis and clarity. Corneal endothelial cells exhibit susceptibility to oxidative stress, suggesting a nuanced relationship between oxidant-antioxidant imbalance and FECD pathogenesis, irrespective of FECD genotype. Given the constrained availability of corneal transplants, exploration into non-surgical interventions becomes crucial. This encompasses traditional antioxidants, small molecule compounds, biologics, and diverse non-drug therapies, such as gene-related therapy, hydrogen therapy and near infrared light therapy. This review concentrates on elucidating the mechanisms behind oxidant-antioxidant imbalance and the evolution of strategies to restore oxidant-antioxidant balance in FECD. It provides a comprehensive overview of both conventional and emerging therapeutic approaches, offering valuable insights for the advancement of non-surgical treatment modalities. The findings herein might establish a robust foundation for future research and the therapeutic strategy of FECD.", "conclusion": "It provides a comprehensive overview of both conventional and emerging therapeutic approaches, offering valuable insights for the advancement of non-surgical treatment modalities. The findings herein might establish a robust foundation for future research and the therapeutic strategy of FECD." }, { "pmid": "39063126", "year": 2024, "title": "The Protective Role of Molecular Hydrogen in Ischemia/Reperfusion Injury.", "title_en": null, "title_de": "Die schützende Rolle von molekularem Wasserstoff bei Ischämie-/Reperfusionsschäden", "journal": "International journal of molecular sciences", "authors": "Kura et al.", "author_search": "kura kura", "doi": "10.3390/ijms25147884", "doi_url": "https://doi.org/10.3390/ijms25147884", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39063126/", "url": "https://h2medicine.org/studies/study-kura-2024-protective-ischemia-reperfusion-injury/", "methods": [ "unspecified" ], "indications": [ "neurology", "cardiovascular", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2024 · Kura — The Protective Role of Molecular Hydrogen in Ischemia/Reperfusion Injury", "summary": "Ischemia/reperfusion injury (IRI) — where tissue damage is paradoxically worsened when blood flow is restored after oxygen deprivation — is a major cause of harm in heart attacks, strokes, and organ transplantation. This review synthesises the evidence that molecular hydrogen (H₂) can mitigate IRI through multiple mechanisms: selectively neutralising damaging ROS, suppressing inflammation, enhancing energy production, reducing calcium overload, and modulating cell death pathways. Further research is needed before H₂ can be routinely integrated into clinical IRI management. This is a literature review.", "assessment": "This is a well-structured narrative review with a broad cross-organ perspective on H₂ in IRI. The multi-mechanism framing is scientifically compelling, and the coverage of cardiac, neurological, renal, hepatic, and transplant IRI models is thorough. However, most evidence cited is preclinical; human clinical trial data for H₂ in IRI is still limited. The authors' call for further research before clinical integration reflects an honest reading of the current evidence base. This review is a solid entry point for understanding H₂'s potential in IRI, not a proof of clinical efficacy.", "abstract": "Ischemia/reperfusion injury (IRI) represents a significant contributor to morbidity and mortality associated with various clinical conditions, including acute coronary syndrome, stroke, and organ transplantation. During ischemia, a profound hypoxic insult develops, resulting in cellular dysfunction and tissue damage. Paradoxically, reperfusion can exacerbate this injury through the generation of reactive oxygen species and the induction of inflammatory cascades. The extensive clinical sequelae of IRI necessitate the development of therapeutic strategies to mitigate its deleterious effects. This has become a cornerstone of ongoing research efforts in both basic and translational science. This review examines the use of molecular hydrogen for IRI in different organs and explores the underlying mechanisms of its action. Molecular hydrogen is a selective antioxidant with anti-inflammatory, cytoprotective, and signal-modulatory properties. It has been shown to be effective at mitigating IRI in different models, including heart failure, cerebral stroke, transplantation, and surgical interventions. Hydrogen reduces IRI via different mechanisms, like the suppression of oxidative stress and inflammation, the enhancement of ATP production, decreasing calcium overload, regulating cell death, etc. Further research is still needed to integrate the use of molecular hydrogen into clinical practice.", "conclusion": "Hydrogen reduces IRI via different mechanisms, like the suppression of oxidative stress and inflammation, the enhancement of ATP production, decreasing calcium overload, regulating cell death, etc. Further research is still needed to integrate the use of molecular hydrogen into clinical practice." }, { "pmid": "38850720", "year": 2024, "title": "Idiopathic sudden sensorineural hearing loss: A review focused on the contribution of vascular pathologies.", "title_en": null, "title_de": "Idiopathischer plötzlicher sensorineuraler Hörverlust: Eine Übersichtsarbeit mit Fokus auf den Beitrag vaskulärer Pathologien", "journal": "Auris, nasus, larynx", "authors": "Tsuzuki et al.", "author_search": "tsuzuki tsuzuki", "doi": "10.1016/j.anl.2024.05.009", "doi_url": "https://doi.org/10.1016/j.anl.2024.05.009", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38850720/", "url": "https://h2medicine.org/studies/study-tsuzuki-2024-idiopathic-sudden-sensorineural-hearing/", "methods": [ "inhalation" ], "indications": [ "diabetes", "metabolic", "neurology", "cardiovascular" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2024 · Tsuzuki — Idiopathic Sudden Sensorineural Hearing Loss: A Review Focused on the Contribution of Vascular Pathologies", "summary": "Idiopathic sudden sensorineural hearing loss (ISSNHL) — an abrupt hearing loss of unknown cause, sometimes with vertigo — is believed to be primarily driven by vascular impairment of the inner ear, including cochlear ischemia and infarction. This review covers the anatomy, clinical features, risk factors, and treatment strategies for ISSNHL, including hydrogen inhalation therapy among several experimental approaches. Importantly, the authors note that no evidence-based treatment currently exists for ISSNHL. This is a literature review.", "assessment": "This is a clinical narrative review centred on ISSNHL pathophysiology and treatment. H₂ inhalation is mentioned as one experimental approach among several — the paper provides no efficacy data for H₂ specifically in ISSNHL. The authors' explicit statement that no evidence-based treatment for ISSNHL currently exists should be taken seriously. The review is valuable for understanding the vascular framework of ISSNHL but does not establish H₂ as an effective intervention. Clinical trials would be needed to determine whether H₂ inhalation provides a meaningful benefit in this condition.", "abstract": "Idiopathic sudden sensorineural hearing loss (ISSNHL) is characterized by abruptly appearing hearing loss, sometimes accompanied by vertigo. Vascular pathologies (e.g., cochlear ischemia, or cochlear infarction) are one of the most likely causes of ISSNHL. This review aims to present current understanding of inner ear anatomy, clinical features of ISSNHL, and its treatment strategies. The labyrinthine artery is the only end artery supplying blood to the inner ear, and it has three branches: the anterior vestibular artery, the main cochlear artery, and the vestibulo-cochlear artery (VCA). Occlusion of the VCA can be caused by a variety of factors. The VCA courses through a narrow bone canal. ISSNHL is usually diagnosed after excluding retrocochlear pathologies of sudden sensorineural hearing loss (SSNHL), such as vestibular schwannoma. Therefore, a head MRI or assessing auditory brainstem responses are recommended for patients with SSNHL. Severe SSNHL patients with high CHADS2 scores, an index of stroke risk, have a significantly lower rate of vestibular schwannoma than severe SSNHL patients with low CHADS2 scores, suggesting that severe ISSNHL in individuals at high risk of stroke is caused by vascular impairments. Intralabyrinthine hemorrhage causes SSNHL or vertigo, as in ISSNHL. The diagnosis of intralabyrinthine hemorrhage requires careful interpretation of MRI, and a small percentage of patients diagnosed with ISSNHL may in fact have intralabyrinthine hemorrhage. Many studies have reported an association between ISSNHL and atherosclerosis or cardiovascular risk factors (e.g., diabetes mellitus, hypertension, dyslipidemia and cardiovascular disease), and subsequent risk of stroke in patients with ISSNHL may be elevated compared to controls. Increased hearing level on the healthy ear side, high Framingham risk score, high neutrophil-to-lymphocyte ratio, high platelet-to-lymphocyte ratio, and severe white matter lesions may be poor prognostic factors for patients with ISSNHL. The association between thrombosis-related genes and susceptibility to ISSNHL has been reported in many studies (e.g., coagulation factor 2, coagulation factor 5, plasminogen activator inhibitor-1, platelet-associated genes, a homocysteine metabolism-related enzyme gene, endothelin-1, nitric oxide 3, phosphodiesterase 4D, complement factor H, and protein kinase C-eta). Treatment of ISSNHL with the aim of mitigating the vascular impairment in the inner ear includes systemically administered steroids, intratympanic steroid injections, hyperbaric oxygen therapy, prostaglandin E1, defibrinogenation therapy, and hydrogen inhalation therapy, but there is currently no evidence-based treatment for ISSNHL. Breakthroughs in the unequivocal diagnosis and treatment of ISSNHL due to vascular impairment are crucial to improve quality of life.", "conclusion": "Treatment of ISSNHL with the aim of mitigating the vascular impairment in the inner ear includes systemically administered steroids, intratympanic steroid injections, hyperbaric oxygen therapy, prostaglandin E1, defibrinogenation therapy, and hydrogen inhalation therapy, but there is currently no evidence-based treatment for ISSNHL. Breakthroughs in the unequivocal diagnosis and treatment of ISSNH" }, { "pmid": "38795643", "year": 2024, "title": "Potential role of molecular hydrogen therapy on oxidative stress and redox signaling in chronic kidney disease.", "title_en": null, "title_de": "Potenzielle Rolle der Therapie mit molekularem Wasserstoff bei oxidativem Stress und Redox-Signalübertragung bei chronischer Nierenerkrankung", "journal": "Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie", "authors": "Zheng et al.", "author_search": "zheng zheng", "doi": "10.1016/j.biopha.2024.116802", "doi_url": "https://doi.org/10.1016/j.biopha.2024.116802", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38795643/", "url": "https://h2medicine.org/studies/study-zheng-2024-oxidative-stress-redox-signaling/", "methods": [ "unspecified" ], "indications": [ "kidney-dialysis", "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2024 · Zheng — Potential Role of Molecular Hydrogen Therapy on Oxidative Stress and Redox Signaling in Chronic Kidney Disease", "summary": "Chronic kidney disease (CKD) is driven in large part by oxidative stress — and current therapies to slow its progression remain inadequate. This review examines how molecular hydrogen (H₂) could address CKD by activating the NRF2-KEAP1 antioxidant defence system, modulating NF-κB inflammation, regulating HIF signalling, and influencing FOXO transcription factors. The authors acknowledge that while preclinical results are encouraging, clinical trials in CKD are still scarce and further investigation is needed. This is a literature review.", "assessment": "This is a mechanistically detailed narrative review that makes a coherent case for H₂ as a candidate adjunct therapy in CKD via multiple redox-signalling pathways. The strength is the pathway-level mechanistic analysis; the weakness is that clinical evidence for H₂ in CKD is sparse and the review does not perform systematic effect-size quantification. The authors appropriately flag this gap. Until adequately powered randomised CKD trials with H₂ are available, clinical conclusions remain provisional.", "abstract": "Oxidative stress plays a key role in chronic kidney disease (CKD) development and progression, inducing kidney cell damage, inflammation, and fibrosis. However, effective therapeutic interventions to slow down CKD advancement are currently lacking. The multifaceted pharmacological effects of molecular hydrogen (H2) have made it a promising therapeutic avenue. H2 is capable of capturing harmful •OH and ONOO- while maintaining the crucial reactive oxygen species (ROS) involved in cellular signaling. The NRF2-KEAP1 system, which manages cell redox balance, could be used to treat CKD. H2 activates this pathway, fortifying antioxidant defenses and scavenging ROS to counteract oxidative stress. H2 can improve NRF2 signaling by using the Wnt/β-catenin pathway and indirectly activate NRF2-KEAP1 in mitochondria. Additionally, H2 modulates NF-κB activity by regulating cellular redox status, inhibiting MAPK pathways, and maintaining Trx levels. Treatment with H2 also attenuates HIF signaling by neutralizing ROS while indirectly bolstering HIF-1α function. Furthermore, H2 affects FOXO factors and enhances the activity of antioxidant enzymes. Despite the encouraging results of bench studies, clinical trials are still limited and require further investigation. The focus of this review is on hydrogen's role in treating renal diseases, with a specific focus on oxidative stress and redox signaling regulation, and it discusses its potential clinical applications.", "conclusion": "Despite the encouraging results of bench studies, clinical trials are still limited and require further investigation. The focus of this review is on hydrogen's role in treating renal diseases, with a specific focus on oxidative stress and redox signaling regulation, and it discusses its potential clinical applications." }, { "pmid": "38707612", "year": 2024, "title": "The Molecular Biological Mechanism of Hydrogen Therapy and Its Application in Spinal Cord Injury.", "title_en": null, "title_de": "Der molekularbiologische Mechanismus der Wasserstofftherapie und ihre Anwendung bei Rückenmarksverletzungen", "journal": "Drug design, development and therapy", "authors": "Hu et al.", "author_search": "hu hu", "doi": "10.2147/dddt.s463177", "doi_url": "https://doi.org/10.2147/dddt.s463177", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38707612/", "url": "https://h2medicine.org/studies/study-hu-2024-biological-mechanism-application-spinal/", "methods": [ "unspecified" ], "indications": [ "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2024 · Hu — The Molecular Biological Mechanism of Hydrogen Therapy and Its Application in Spinal Cord Injury", "summary": "Spinal cord injury (SCI) causes devastating neurological damage and has very limited treatment options. This review summarises the molecular biology of hydrogen therapy and its potential application in SCI, drawing on animal experiments and in vitro cell studies showing anti-inflammatory, antioxidant, and anti-apoptotic effects. The authors provide preliminary evidence that H₂ may have protective effects in SCI models, but note that clinical application is still at an early stage. This is a literature review, not a human trial.", "assessment": "This is a narrative review drawing on preclinical (animal and in vitro) evidence for H₂ in SCI. The mechanistic case for H₂'s neuroprotective properties is plausible and built on a consistent body of animal data. However, clinical evidence in human SCI is scarce, and SCI is notoriously difficult to treat — preclinical success does not reliably predict clinical benefit in this field. The review itself frames the evidence as ‚preliminary'. Readers should not interpret this as clinical proof of H₂ efficacy in spinal cord injury.", "abstract": "Hydrogen, which is a novel biomedical molecule, is currently the subject of extensive research involving animal experiments and in vitro cell experiments, and it is gradually being applied in clinical settings. Hydrogen has been proven to possess anti-inflammatory, selective antioxidant, and antiapoptotic effects, thus exhibiting considerable protective effects in various diseases. In recent years, several studies have provided preliminary evidence for the protective effects of hydrogen on spinal cord injury (SCI). This paper provides a comprehensive review of the potential molecular biology mechanisms of hydrogen therapy and its application in treating SCI, with an aim to better explore the medical value of hydrogen and provide new avenues for the adjuvant treatment of SCI.", "conclusion": "In recent years, several studies have provided preliminary evidence for the protective effects of hydrogen on spinal cord injury (SCI). This paper provides a comprehensive review of the potential molecular biology mechanisms of hydrogen therapy and its application in treating SCI, with an aim to better explore the medical value of hydrogen and provide new avenues for the adjuvant treatment of SCI." }, { "pmid": "38661046", "year": 2024, "title": "Exploring approaches to pulp vitality assessment: A scoping review of nontraditional methods.", "title_en": null, "title_de": "Untersuchung von Ansätzen zur Beurteilung der Pulpavitalität: Ein Scoping Review nichttraditioneller Methoden", "journal": "International endodontic journal", "authors": "Afkhami et al.", "author_search": "afkhami afkhami", "doi": "10.1111/iej.14073", "doi_url": "https://doi.org/10.1111/iej.14073", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38661046/", "url": "https://h2medicine.org/studies/study-afkhami-2024-exploring-approaches-pulp-vitality/", "methods": [ "inhalation" ], "indications": [ "skin-aging", "oral-health" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2024 · Afkhami — Exploring Approaches to Pulp Vitality Assessment: A Scoping Review of Nontraditional Methods", "summary": "Accurate assessment of dental pulp vitality is critical in endodontics — yet current clinical tests are imprecise. This scoping review systematically surveys 65 non-traditional techniques for assessing pulp vitality, including optical methods, MRI, ultrasound Doppler, terahertz imaging, and invasive approaches such as hydrogen gas desaturation. H₂ appears here in a diagnostic context (using hydrogen to assess blood flow in the pulp), not as a therapeutic agent. This is a systematic scoping review.", "assessment": "This scoping review is methodologically sound and provides a useful landscape of emerging pulp vitality assessment techniques. It is important to note that H₂'s appearance here is strictly diagnostic — hydrogen gas desaturation uses H₂ as a tracer to quantify pulpal blood flow, and has no relationship to the systemic H₂ therapy literature. Readers interested in H₂ as a therapeutic agent should note this study is not relevant to that topic.", "abstract": "INTRODUCTION: Diagnostic procedures for pulp vitality assessment are a crucial aspect of routine dental practice. This review aims to provide a comprehensive overview of nontraditional techniques and methodologies for assessing pulp vitality, specifically exploring promising approaches that are currently not used in dental practice. METHODS: The study protocol was registered a priori (https://osf.io/3m97z/). An extensive electronic search was conducted across multiple databases, including MEDLINE via PubMed, Scopus, Web of Science, and Embase. Inclusion criteria were guided by the research question based on the PCC model as follows: \"What are the potential nontraditional techniques (Concept) for assessing pulp vitality (Population) in the field of endodontics or clinical practice (Context)?\" Studies were included that explored possible approaches to pulp vitality assessment, utilizing a range of techniques, whilst any studies using traditional pulp tests (cold, heat, and electric stimulation) or well-known methods (pulse oximetry and laser Doppler flowmetry) were excluded. Reviewers independently screened articles and extracted data. A patent search was also performed. RESULTS: Of 3062 studies, 65 were included that described nontraditional approaches for assessing pulp vitality. These included a range of optical diagnostic methods, ultrasound Doppler flowmetry (UDF), magnetic resonance imaging (MRI), terahertz imaging, tooth temperature measurements, as well as invasive methodologies, including 133xenon washout, radioisotope-labelled tracers, hydrogen gas desaturation, intravital microscopy and fluorescent microspheres isotope clearance. The patent search included artificial intelligence and biomarkers methods. CONCLUSIONS: This review provides details for potential innovative tests that may directly describe pulp vitality. Importantly, these methods range from clinically impractical through to promising methods that may transform clinical practice. Several nontraditional techniques have the potential to enhance diagnostic accuracy and could provide valuable insights into the assessment of pulp vitality in challenging clinical scenarios.", "conclusion": "This review provides details for potential innovative tests that may directly describe pulp vitality. Importantly, these methods range from clinically impractical through to promising methods that may transform clinical practice. Several nontraditional techniques have the potential to enhance diagnostic accuracy and could provide valuable insights into the assessment of pulp vitality in challenging clinical scenarios." }, { "pmid": "38638053", "year": 2024, "title": "The Therapeutic Application of Hydrogen in Cancer: The Potential and Challenges.", "title_en": null, "title_de": "Die therapeutische Anwendung von Wasserstoff bei Krebs: Das Potenzial und die Herausforderungen", "journal": "Current pharmaceutical design", "authors": "Khiji et al.", "author_search": "khiji khiji", "doi": "10.2174/0113816128296710240404040232", "doi_url": "https://doi.org/10.2174/0113816128296710240404040232", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38638053/", "url": "https://h2medicine.org/studies/study-khiji-2024-therapeutic-application-cancer-challenges/", "methods": [ "unspecified" ], "indications": [ "cancer", "immune-system", "oxidative-stress", "fundamentals-safety" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2024 · Khiji — The Therapeutic Application of Hydrogen in Cancer: The Potential and Challenges", "summary": "Cancer is frequently associated with oxidative stress and chronic inflammation, and this review examines molecular hydrogen (H₂) as a candidate supportive therapy that could help prevent cancer recurrence and reduce treatment side effects. Preclinical studies show H₂ can enhance the effectiveness of conventional treatments in several cancer types. However, the authors explicitly state that further clinical trials are needed to clarify safety, optimal dosage, and mechanisms before H₂ can be recommended clinically. This is a literature review.", "assessment": "This is a narrative review presenting a balanced overview of H₂'s potential in oncology. The mechanistic rationale is scientifically coherent, and the preclinical evidence is multi-cancer and broadly consistent. However, clinical evidence is described as limited, and the review itself calls for additional trials. H₂ as a cancer therapy adjunct remains investigational — it should not be presented as an established treatment. The authors' conclusion that H₂ is ‚innovative and promising' accurately reflects the current evidence level.", "abstract": "Hydrogen therapy has emerged as a possible approach for both preventing and treating cancer. Cancers are often associated with oxidative stress and chronic inflammation. Hydrogen, with its unique physiological functions and characteristics, exhibits antioxidant, anti-inflammatory, and anti-apoptotic properties, making it an attractive candidate for cancer treatment. Through its ability to mitigate oxidative damage, modulate inflammatory responses, and sustain cellular viability, hydrogen demonstrates significant potential in preventing cancer recurrence and improving treatment outcomes. Preclinical studies have shown the efficacy of hydrogen therapy in several cancer types, highlighting its ability to enhance the effectiveness of conventional treatments while reducing associated side effects. Furthermore, hydrogen therapy has been found to be safe and well-tolerated in clinical settings. Nonetheless, additional investigations are necessary to improve a comprehensive understanding of the mechanisms underlying hydrogen's therapeutic potential and refine the administration and dosage protocols. However, further clinical trials are still needed to explore its safety profile and capacity. In aggregate, hydrogen therapy represents an innovative and promising treatment for several malignancies.", "conclusion": "However, further clinical trials are still needed to explore its safety profile and capacity. In aggregate, hydrogen therapy represents an innovative and promising treatment for several malignancies." }, { "pmid": "38615891", "year": 2024, "title": "The role of hydrogen in the prevention and treatment of coronary atherosclerotic heart disease.", "title_en": null, "title_de": "Die Rolle von Wasserstoff bei der Prävention und Behandlung der koronaren atherosklerotischen Herzkrankheit", "journal": "European journal of pharmacology", "authors": "Chen et al.", "author_search": "chen chen", "doi": "10.1016/j.ejphar.2024.176586", "doi_url": "https://doi.org/10.1016/j.ejphar.2024.176586", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38615891/", "url": "https://h2medicine.org/studies/study-chen-2024-prevention-coronary-atherosclerotic-heart/", "methods": [ "unspecified" ], "indications": [ "metabolic", "cardiovascular", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2024 · Chen — The Role of Hydrogen in the Prevention and Treatment of Coronary Atherosclerotic Heart Disease", "summary": "Coronary atherosclerotic heart disease (CHD) — the most common cardiovascular disease worldwide — is driven by chronic inflammation and oxidative lipid deposition in arterial walls. This review examines how molecular hydrogen (H₂) could contribute to CHD prevention and treatment by targeting multiple inflammatory and metabolic pathways simultaneously, including NF-κB, Nrf2, PI3K, and AMPK signalling. This is a literature review; no new experimental data are presented.", "assessment": "This is a mechanistically detailed narrative review that builds a plausible multi-pathway case for H₂ in CHD. The mechanistic analysis is thorough and scientifically coherent. However, clinical evidence for H₂ in CHD is sparse, and the review serves primarily to organise the preclinical and mechanistic landscape and guide future research design — not to prove clinical efficacy. Readers should not interpret this review as evidence that H₂ prevents or treats CHD in humans.", "abstract": "Coronary atherosclerotic heart disease (CHD) is a primary cardiovascular disease caused by atherosclerosis (AS), which is characterized by chronic inflammation and lipid oxidative deposition. Molecular hydrogen (H2) is an effective anti-inflammatory agent and has potential to ameliorate glycolipid metabolism disorders, which is believed to exert beneficial effects on the prevention and treatment of CHD. It is suggested that H2 reduces inflammation in CHD by regulating multiple pathways, including NF-κB inflammatory pathway, pyroptosis, mitophagy, endoplasmic reticulum (ER) stress, and Nrf2 antioxidant pathway. Additionally, H2 may improve glycolipid metabolism by mediation of PI3K and AMPK signalling pathways, contributing to inhibition of the occurrence and development of CHD. This review elaborates pathogenesis of CHD and evaluates the role of H2 in CHD. Moreover, possible molecular mechanisms have been discussed and speculated, aiming to provide more strategies and directions for subsequent studies of H2 in CHD.", "conclusion": "This review elaborates pathogenesis of CHD and evaluates the role of H2 in CHD. Moreover, possible molecular mechanisms have been discussed and speculated, aiming to provide more strategies and directions for subsequent studies of H2 in CHD." }, { "pmid": "38377746", "year": 2024, "title": "Catalytic innovations: Improving wastewater treatment and hydrogen generation technologies.", "title_en": null, "title_de": "Katalytische Innovationen: Verbesserung von Abwasserbehandlungs- und Wasserstofferzeugungstechnologien.", "journal": "Journal of environmental management", "authors": "Khan et al.", "author_search": "khan khan", "doi": "10.1016/j.jenvman.2024.120228", "doi_url": "https://doi.org/10.1016/j.jenvman.2024.120228", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38377746/", "url": "https://h2medicine.org/studies/study-khan-2024-catalytic-innovations-improving-wastewater/", "methods": [ "inhalation" ], "indications": [ "other" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2024 · Khan — Catalytic innovations: Improving wastewater treatment and hydrogen generation technologies.", "summary": "Nanomaterials as catalysts can both clean wastewater of toxic organic pollutants and simultaneously generate hydrogen gas — a dual benefit reviewed here. NaBH₄ methanolysis using nanocatalysts is highlighted as a particularly efficient route. The review evaluates catalyst performance across key parameters including size, reaction rate, activation energy, and durability. (Journal of Environmental Management, 2024.)", "assessment": "This is a technical review with no original experimental data — it synthesises existing literature on nanocatalytic systems for combined wastewater treatment and H₂ generation. Important context: this paper concerns industrial/environmental hydrogen production and pollutant remediation, not therapeutic or health-related hydrogen use in humans or animals. The H₂ discussed here is an energy carrier by-product, not a medicinal agent. The review is a useful resource for researchers in materials science and environmental engineering, but does not provide evidence for any health benefit of H₂ in biological systems.", "abstract": "The effective reduction of hazardous organic pollutants in wastewater is a pressing global concern, necessitating the development of advanced treatment technologies. Pollutants such as nitrophenols and dyes, which pose significant risks to both human and aquatic health, making their reduction particularly crucial. Despite the existence of various methods to eliminate these pollutants, they are not without limitations. The utilization of nanomaterials as catalysts for chemical reduction exhibits a promising alternative owing to their distinguished catalytic activity and substantial surface area. For catalytically reducing the pollutants NaBH4 has been utilized as a useful source for it because it reduces the pollutants quiet efficiently and it also releases hydrogen gas as well which can be used as a source of energy. This paper provides a comprehensive review of recent research on different types of nanomaterials that function as catalysts to reduce organic pollutants and also generating hydrogen from NaBH4 methanolysis while also evaluating the positive and negative aspects of nanocatalyst. Additionally, this paper examines the features effecting the process and the mechanism of catalysis. The comparison of different catalysts is based on size of catalyst, reaction time, rate of reaction, hydrogen generation rate, activation energy, and durability. The information obtained from this paper can be used to steer the development of new catalysts for reducing organic pollutants and generation hydrogen by NaBH4 methanolysis.", "conclusion": "The comparison of different catalysts is based on size of catalyst, reaction time, rate of reaction, hydrogen generation rate, activation energy, and durability. The information obtained from this paper can be used to steer the development of new catalysts for reducing organic pollutants and generation hydrogen by NaBH4 methanolysis." }, { "pmid": "38532373", "year": 2024, "title": "The effect of hydrogen-rich water consumption on premenstrual symptoms and quality of life: a randomized controlled trial", "title_en": null, "title_de": "Die Wirkung des Konsums von wasserstoffreichem Wasser auf prämenstruelle Symptome und Lebensqualität: eine randomisierte kontrollierte Studie", "journal": "BMC Women's Health", "authors": "Aker et al.", "author_search": "aker aker", "doi": "10.1186/s12905-024-03029-8", "doi_url": "https://doi.org/10.1186/s12905-024-03029-8", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38532373/", "url": "https://h2medicine.org/studies/study-aker-2024-premenstrual-symptoms-quality-of-life/", "methods": [ "drinking-hrw" ], "indications": [ "womens-health", "oxidative-stress" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2024 · Aker — The effect of hydrogen-rich water consumption on premenstrual symptoms and quality of life: a randomized controlled trial", "summary": "Hydrogen-rich water lowers premenstrual complaints and boosts quality of life. In a randomized controlled trial (n = 65) over three menstrual cycles, the H₂ group had significantly lower PMS scores and, at the first follow-up, higher physical and psychological quality of life than the control (p (BMC Women's Health, 2024.)", "assessment": "Relevant for H₂ water applications in women's health — a concrete, everyday indication with a large affected population. Mechanistically the finding fits the antioxidant/anti-inflammatory profile of H₂. A co-author is Tyler W. LeBaron, a well-known figure in H₂ research (Molecular Hydrogen Institute) — that strengthens the subject expertise, but should also be noted as a possible conflict of interest. Limitation, stated honestly: a moderate sample (n = 65), the abstract mentions no blinding (presumably an open design), and the endpoints (PMS symptoms, quality of life) are subjective questionnaires that can respond to expectation effects. The quality-of-life advantage was also significant only at one follow-up, not across the whole time course.", "abstract": "BACKGROUND: Premenstrual syndrome (PMS) consists of psychiatric or somatic symptoms negatively affecting the daily life. PMS treatment can involve the use of complementary-alternative approaches. Hydrogen-rich water (HRW) has antioxidant and anti-inflammatory properties that may treat PMS. This study aimed to investigate the effect of drinking HRW on the severity of premenstrual symptoms and the quality of life of women who suffer from PMS. METHODS: This study is a randomized controlled trial. Participants were randomized into two groups (intervention group=33, control group=32) using the block randomization method. Participants were requested to consume 1500-2000 mL of HRW daily in the intervention group and drink water in the placebo group. Participants began drinking either HRW or placebo water from day 16 of their menstrual cycle until day 2 of the following cycle for three menstrual cycles. The research data were collected using a Demographic Information Form, Premenstrual Syndrome Scale (PMSS), and Short form of the World Health Organization Quality of Life Questionnaire (WHOQOL- BREF). RESULTS: The intervention group had significantly lower mean scores than the control group in both the first and second follow-ups on the PMSS (P<0.05). In the first follow-up, the intervention group had significantly higher mean scores in the Physical Health and Psychological domains of the WHOQOL-BREF compared to the control group (P<0.05). Group × time interaction was significant for PMSS (F = 10.54, P<0.001). Group × time interaction was insignificant for WHOQOL- BREF (P>0.05). CONCLUSIONS: The consumption of HRW reduces the severity of premenstrual symptoms and improves individuals' quality of life in physical and psychological domains.", "conclusion": "The consumption of HRW reduces the severity of premenstrual symptoms and improves individuals' quality of life in physical and psychological domains." }, { "pmid": "38996821", "year": 2024, "title": "The impact of hydrogen inhalation therapy on blood reactive oxygen species levels: A randomized controlled study", "title_en": null, "title_de": "Der Einfluss einer Wasserstoff-Inhalationstherapie auf den Spiegel reaktiver Sauerstoffspezies im Blut: eine randomisierte kontrollierte Studie", "journal": "Free Radical Biology & Medicine", "authors": "Chair et al.", "author_search": "chair chair", "doi": "10.1016/j.freeradbiomed.2024.07.010", "doi_url": "https://doi.org/10.1016/j.freeradbiomed.2024.07.010", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38996821/", "url": "https://h2medicine.org/studies/study-chair-2024-inhalation-reactive-oxygen-species/", "methods": [ "inhalation" ], "indications": [ "oxidative-stress", "fundamentals" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2024 · Chair — The impact of hydrogen inhalation therapy on blood reactive oxygen species levels: A randomized controlled study", "summary": "Inhaling hydrogen measurably lowers free oxygen radicals in the blood. In a controlled study of people with elevated ROS levels (d-ROMs > 350 U.CARR), a single session of hydrogen inhalation significantly reduced the blood ROS level — right after treatment. (Free Radical Biology & Medicine, 2024.)", "assessment": "Valuable as direct human evidence for the antioxidant core promise of H₂: it measures oxidative stress (ROS) in the blood and shows a significant reduction after H₂ inhalation. It thus bridges from preclinical mechanism (Ohsawa 2007) to clinical measurement. Relevant for H₂ inhalation applications. Limitation, stated honestly: a small sample (n = 37), the abstract provides no concrete effect sizes, means or p-values, and the measured endpoint is a biomarker (d-ROMs), not a symptom or clinical outcome. Published in a relevant specialist journal (Free Radical Biology & Medicine).", "abstract": "Reactive Oxygen Species (ROS) play a key role in physiological processes. However, the imbalance between ROS and antioxidants in favor of the former causes oxidative stress linked to numerous pathologies. Due to its unique attributes, including distinguished permeability and selective antioxidant capability, molecular hydrogen (H2) has become an essential therapeutic agent. Hydrogen Inhalation Therapy (HIT) has come to light as a promising strategy to counteract oxidative stress. In this randomized controlled study, we aimed to evaluate the effectiveness of HIT in reducing blood ROS levels. 37 participants with elevated ROS levels (d-ROMs value > 350 U.CARR) were enrolled in the study. Participants were divided into test and control groups. The test group participants received HIT, and then their blood ROS levels were measured immediately post-treatment and after 24 h. Their results were compared to those of the control group participants who did not undergo HIT. The test group demonstrated a significant reduction in blood ROS levels after the treatment. These findings suggested the efficacy of HIT in reducing oxidative stress.", "conclusion": "The test group demonstrated a significant reduction in blood ROS levels after the treatment. These findings suggested the efficacy of HIT in reducing oxidative stress." }, { "pmid": "39703911", "year": 2024, "title": "Hydrogen gas inhalation prior to high-intensity training reduces attenuation of nitric oxide bioavailability in male rugby players", "title_en": null, "title_de": "Das Einatmen von Wasserstoffgas vor intensivem Training reduziert die Abnahme der Stickstoffmonoxid-Verfügbarkeit bei männlichen Rugby-Spielern", "journal": "PeerJ", "authors": "Zhao et al.", "author_search": "zhao zhao", "doi": "10.7717/peerj.18503", "doi_url": "https://doi.org/10.7717/peerj.18503", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39703911/", "url": "https://h2medicine.org/studies/study-zhao-2024-gas-inhalation-nitric-oxide-rugby-players/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "sports-exercise", "oxidative-stress", "cardiovascular" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2024 · Zhao — Hydrogen gas inhalation prior to high-intensity training reduces attenuation of nitric oxide bioavailability in male rugby players", "summary": "Inhaling hydrogen protects the nitric oxide signal after hard training. In a randomized double-blind crossover in professional rugby players, H₂ inhalation kept post-exercise nitric oxide (NO) levels and their precursors higher, lowered oxidative-damage and inflammation markers, and increased total antioxidant capacity. (PeerJ, 2024.)", "assessment": "Relevant for H₂ inhalation applications in competitive sport because it shows a plausible mechanism: preservation of the vasodilating NO signal plus dampening of inflammation and oxidative stress after exertion. The crossover double-blind design makes the statement robust, since each player is his own control. Limitation, stated honestly: a very small, highly specialized population (professional rugby, men only), a short intervention period, exact sample size not given in the abstract — a biomarker study, not a direct performance endpoint. The DOI stored in the dataset belongs to an unrelated paper (Antioxidants & Redox Signaling, 2011) and was therefore deliberately omitted.", "abstract": "BACKGROUND: Inhalation of hydrogen gas (H2) as an antioxidant supplement may alleviate exercise-induced oxidative damage and protect post-exercise hydrogen peroxide signaling, which may help mediate beneficial exercise adaptation. The aims of this study were to determine the effects of H2 inhalation on plasma nitric oxide (NO) level and its synthesis precursor in professional athletes. METHODS: A randomized, placebo-controlled, double-blind, crossover trial was conducted with professional male rugby players for 3 weeks. Participants underwent 1 week of H2 supplementation and 1 week of placebo treatment prior to daily sessions of high-intensity exercise training, separated by 1 week of low-intensity training as a washout. RESULTS: Two-way (supplementation and time) repeated-measures analyses of variance showed that NO, L-arginine, and tetrahydrobiopterin levels in the H2 inhalation group were significantly higher than those in the placebo group after exercise (D6) and remained higher after 24 h of rest (D7). Levels of hydroxydeoxyguanosine and interleukin 6 were lower in the H2 inhalation week than in the placebo week on D6 and D7. In addition, total antioxidant levels were significantly higher with H2 inhalation than with placebo. SIGNIFICANCE: These results suggest that H2 inhalation helps to maintain NO signaling after exercise and to alleviate inflammation and oxidative stress induced by high-intensity exercise training in professional athletes.", "conclusion": "In addition, total antioxidant levels were significantly higher with H2 inhalation than with placebo. SIGNIFICANCE: These results suggest that H2 inhalation helps to maintain NO signaling after exercise and to alleviate inflammation and oxidative stress induced by high-intensity exercise training in professional athletes." }, { "pmid": "39064785", "year": 2024, "title": "Hydrogen-Rich Gas Enhanced Sprint-Interval Performance: Metabolomic Insights into Underlying Mechanisms.", "title_en": null, "title_de": "Wasserstoffreiches Gas verbessert die Sprint-Intervall-Leistung: Metabolomische Einblicke in die zugrunde liegenden Mechanismen", "journal": "Nutrients", "authors": "Dong et al.", "author_search": "dong dong", "doi": "10.3390/nu16142341", "doi_url": "https://doi.org/10.3390/nu16142341", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39064785/", "url": "https://h2medicine.org/studies/study-dong-2024-enhanced-sprint-interval-performance/", "methods": [ "inhalation" ], "indications": [ "metabolic", "sports-exercise" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2024 · Dong — Hydrogen-Rich Gas Enhanced Sprint-Interval Performance: Metabolomic Insights into Underlying Mechanisms", "summary": "Inhaling hydrogen-rich gas (HRG) for 60 minutes before a sprint-interval test improved late-stage anaerobic performance and reduced performance decline across sprints in healthy men. Metabolomic analysis revealed that H₂ inhalation upregulated several metabolites linked to fat mobilization and coenzyme A synthesis, suggesting a mechanism involving accelerated fat oxidation to replenish ATP during interval recovery. (Nutrients, 2024.)", "assessment": "A well-designed small crossover study that advances H₂ sports science from \"does it work?\" toward \"how might it work?\". The metabolomics data is genuinely novel and the performance improvements in late-stage sprints are biologically plausible. Key limitations: n=10 is very small — results need replication in a larger sample; only healthy men were studied; the metabolomic pathway analysis is associative, not causal (enrichment analysis cannot prove that the identified pathways are responsible for the performance effect). The H₂ inhalation protocol (60 min pre-exercise) is practically realistic. Overall: promising mechanistic signal, but preliminary.", "abstract": "(1) Background: The diversity of blood biomarkers used to assess the metabolic mechanisms of hydrogen limits a comprehensive understanding of its effects on improving exercise performance. This study evaluated the impact of hydrogen-rich gas (HRG) on metabolites following sprint-interval exercise using metabolomics approaches, aiming to elucidate its underlying mechanisms of action. (2) Methods: Ten healthy adult males participated in the Wingate Sprint-interval test (SIT) following 60 min of HRG or placebo (air) inhalation. Venous blood samples were collected for metabolomic analysis both before and after gas inhalation and subsequent to completing the SIT. (3) Results: Compared with the placebo, HRG inhalation significantly improved mean power, fatigue index, and time to peak for the fourth sprint and significantly reduced the attenuation values of peak power, mean power, and time to peak between the first and fourth. Metabolomic analysis highlighted the significant upregulation of acetylcarnitine, propionyl-L-carnitine, hypoxanthine, and xanthine upon HRG inhalation, with enrichment pathway analysis suggesting that HRG may foster fat mobilization by enhancing coenzyme A synthesis, promoting glycerophospholipid metabolism, and suppressing insulin levels. (4) Conclusions: Inhaling HRG before an SIT enhances end-stage anaerobic sprint capabilities and mitigates fatigue. Metabolomic analysis suggests that HRG may enhance ATP recovery during interval stages by accelerating fat oxidation, providing increased energy replenishment for late-stage sprints.", "conclusion": "Inhaling HRG before an SIT enhances end-stage anaerobic sprint capabilities and mitigates fatigue. Metabolomic analysis suggests that HRG may enhance ATP recovery during interval stages by accelerating fat oxidation, providing increased energy replenishment for late-stage sprints." }, { "pmid": "38698624", "year": 2024, "title": "Inhalation of Hydrogen-rich Gas before Acute Exercise Alleviates Exercise Fatigue: A Randomized Crossover Study.", "title_en": null, "title_de": "Inhalation von wasserstoffreichem Gas vor akuter Belastung lindert die Belastungsermüdung: Eine randomisierte Crossover-Studie", "journal": "International journal of sports medicine", "authors": "Dong et al.", "author_search": "dong dong", "doi": "10.1055/a-2318-1880", "doi_url": "https://doi.org/10.1055/a-2318-1880", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38698624/", "url": "https://h2medicine.org/studies/study-dong-2024-inhalation-before-acute-exercise/", "methods": [ "inhalation" ], "indications": [ "sports-exercise", "oxidative-stress" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2024 · Dong — Inhalation of Hydrogen-Rich Gas before Acute Exercise Alleviates Exercise Fatigue: A Randomized Crossover Study", "summary": "Pre-exercise inhalation of hydrogen-rich gas (HRG) reduced subjective fatigue, improved cycling performance during the final phase of exhaustion trials, and lowered post-exercise lactate and oxidative stress markers in healthy men — compared to placebo air inhalation. Not all measures improved: counter-movement jump height and glutathione peroxidase activity showed no significant difference between HRG and placebo. (International Journal of Sports Medicine, 2024.)", "assessment": "A methodologically solid small crossover study with an honest mixed result. Positive: fatigue perception, lactate, hydroxyl radical inhibition, and late-phase cycling frequency all improved significantly with HRG vs. placebo. Null findings (explicitly reported): counter-movement jump height did not improve, and glutathione peroxidase activity was unchanged — important limits on what H₂ inhalation actually does in this context. Key limitations: n=24 (only men), single exercise modality (cycling), no information on H₂ concentration in inhaled gas. The crossover design controls for individual variation well. Overall: suggestive positive effect on fatigue and lactate with documented null findings for explosive power.", "abstract": "Hydrogen, as an antioxidant, may have the potential to mitigate fatigue and improve selected oxidative stress markers induced by strenuous exercise. This study focused on a previously unexplored approach involving pre-exercise inhalation of hydrogen-rich gas (HRG). Twenty-four healthy adult men first completed pre-laboratories to determine maximum cycling power (Wmax) and maximum cycling time (Tmax). Then they were subjected to ride Tmax at 80% Wmax and 60-70 rpm on cycle ergometers after inhaled HRG or placebo gas (air) for 60-minute in a double-blind, counterbalanced, randomized, and crossover design. The cycling frequency in the fatigue modeling process and the rating of perceived exertion (RPE) at the beginning and end of the ride were recorded. Before gas inhalation and after fatigue modeling, visual analog scale (VAS) for fatigue and counter-movement jump (CMJ) were tested, and blood samples were obtained. The results showed that compared to a placebo, HRG inhalation induced significant improvement in VAS, RPE, the cycling frequency during the last 30 seconds in the fatigue modeling process, the ability to inhibit hydroxyl radicals, and serum lactate after exercise (p<0.028), but not in CMJ height and glutathione peroxidase activity. The cycling frequency during the last 30 seconds of all other segments in the fatigue modeling process was within the range of 60-70 rpm. In conclusion, HRG inhalation prior to acute exercise can alleviate exercise-induced fatigue, maintain functional performance, and improve hydroxyl radical and lactate levels.", "conclusion": "The cycling frequency during the last 30 seconds of all other segments in the fatigue modeling process was within the range of 60-70 rpm. In conclusion, HRG inhalation prior to acute exercise can alleviate exercise-induced fatigue, maintain functional performance, and improve hydroxyl radical and lactate levels." }, { "pmid": "38232698", "year": 2024, "title": "Early time-restricted eating improves markers of cardiometabolic health but has no impact on intestinal nutrient absorption in healthy adults.", "title_en": null, "title_de": "Frühes zeitlich begrenztes Essen verbessert Marker der kardiometabolischen Gesundheit, hat aber keinen Einfluss auf die intestinale Nährstoffaufnahme bei gesunden Erwachsenen.", "journal": "Cell reports. Medicine", "authors": "Dawson et al.", "author_search": "dawson dawson", "doi": "10.1016/j.xcrm.2023.101363", "doi_url": "https://doi.org/10.1016/j.xcrm.2023.101363", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38232698/", "url": "https://h2medicine.org/studies/study-dawson-2024-early-time-restricted-eating/", "methods": [], "indications": [ "diabetes", "cardiovascular" ], "evidence_level": 3, "human": true, "therapeutic": false, "h2category": "breath-test", "headline": "2024 · Dawson — Early time-restricted eating improves markers of cardiometabolic health but has no impact on intestinal nutrient absorption in healthy adults.", "summary": "Eating only between 08:00 and 14:00 (early time-restricted eating, eTRE) improved blood glucose regulation in healthy adults — but left gut function completely untouched. A randomised crossover trial with 16 participants showed lower 24-hour mean glucose and reduced glycaemic variability, while intestinal absorption, transit time, and gut microbiome composition remained unchanged. (Cell Reports Medicine, 2024.)", "assessment": "A well-controlled study with an honest null result on gut function. The colonic hydrogen gas production data is incidental but scientifically useful: it demonstrates that short-term (9-day) changes in meal timing do not alter fermentation-based H₂ output. Limitations: n=16 is small; the 9-day intervention window may be too short to detect microbiome shifts; only healthy adults were studied, limiting generalisability to metabolic disease populations. The eTRE metabolic findings are encouraging but require longer trials in larger cohorts before clinical recommendations can be drawn.", "abstract": "Early time-restricted eating (eTRE) improves aspects of cardiometabolic health. Although the circadian system appears to regulate nutrient absorption, little is known about the effects of eTRE on intestinal absorption. In this randomized crossover trial, 16 healthy adults follow a controlled, weight maintenance diet for 9 days, consuming all calories between 0800 and 1400 (eTRE schedule) or 0800 and 2000 (control schedule). We measure the energy content of the diet, stool, and urine with bomb calorimetry and calculate intestinal energy absorption. The eTRE schedule is more effective than the control eating schedule for improving markers of cardiometabolic health, including 24-h mean glucose concentrations and glycemic variability, assessed as the mean amplitude of glycemic excursions. However, eTRE has no effect on intestinal energy and macronutrient absorption, gastrointestinal transit time, colonic hydrogen gas production, or stool microbial composition, suggesting eTRE does not impact gastrointestinal function. This trial is registered (ClinicalTrials.gov: NCT04877262).", "conclusion": "However, eTRE has no effect on intestinal energy and macronutrient absorption, gastrointestinal transit time, colonic hydrogen gas production, or stool microbial composition, suggesting eTRE does not impact gastrointestinal function. This trial is registered (ClinicalTrials.gov: NCT04877262)." }, { "pmid": "38713041", "year": 2024, "title": "[Rehabilitation program of post-COVID-19 syndrome with the use of nitric oxide and molecular hydrogen].", "title_en": null, "title_de": "Rehabilitationsprogramm des Post-COVID-19-Syndroms unter Einsatz von Stickstoffmonoxid und molekularem Wasserstoff", "journal": "Terapevticheskii Arkhiv", "authors": "Pozdnyakova et al.", "author_search": "pozdnyakova pozdnyakova", "doi": "10.26442/00403660.2024.03.202639", "doi_url": "https://doi.org/10.26442/00403660.2024.03.202639", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38713041/", "url": "https://h2medicine.org/studies/study-pozdnyakova-2024-nitric-oxide-post-covid-19-rehabilitation/", "methods": [ "inhalation" ], "indications": [ "respiratory", "oxidative-stress", "cardiovascular" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2024 · Pozdnyakova — Rehabilitation program of post-COVID-19 syndrome with the use of nitric oxide and molecular hydrogen", "summary": "The combined inhalation of nitric oxide and hydrogen improved complaints in post-COVID syndrome. In an open controlled study (n = 34), shortness of breath, cough, fatigue and palpitations decreased, quality of life rose, and oxidative stress fell (p (Terapevticheskii Arkhiv, 2024.)", "assessment": "Relevant because post-COVID is a large, still-current affected group and H₂ is tested here as part of a respiratory-gas therapy; the findings on oxidative stress and microcirculation fit the H₂ profile mechanistically. Most important limitation, stated honestly: the intervention was a combination of NO and H₂ — the contribution of hydrogen alone cannot be isolated from this design (confounding by NO). Added to this are a small sample (n = 34), an open design without sham treatment in the control group (placebo/attention effects possible) and subjective questionnaire endpoints. A supportive signal, not isolated proof of H₂ efficacy.", "abstract": "UNLABELLED: Рost-COVID-19 syndrome (PS) is one of the medical and social problem. According to WHO, 10-20% of COVID-19 patients suffer from PS. The use of medical gases - inhaled nitric oxide (iNO) and molecular hydrogen (iH2) - may influence on the mechanisms of development PC. AIM: To evaluate the safety and efficacy of the combined inhalation of NO and H2 (iNO/iH2) in patients with respiratory manifestations of PS. MATERIALS AND METHODS: 34 patients with PS (11 men/23 women, 60.0±11.7 years) were included in the prospective open-label controlled study in parallel groups: the main group (n=17) received iNO/iH2 for 90 minutes once a day for 10 days (concentration of NO 60 ppm, H2<4% in the gas mixture), the control group (n=17) didn't receive inhalations. The period from the confirmation of COVID-19 to the start of the study was 641.8±230.5 days. The groups did not differ in the baseline parameters. The clinical symptoms (from the self-observation diary and mMRC questionnaires, \"dyspnea language\"), FAS, HADS, SF-36 scores, 6-minute walk test, the blood serum parameters of oxidative stress, the dynamics of the microcirculation in the eye bulbar conjunctiva were evaluated. The individual dose of iNO has chosen during a 15-minute test (the positive dynamics of the microcirculation have indicated that the dose was selected correctly). RESULTS: The decrease the symptoms severity, such as dyspnea, cough, fatigue and palpitations (p<0.005), the increase in SF-36 questionnaire scores (p=0.006) and a reducing of FAS score (p=0.001), as well as the anxiety component of HADS (p=0.02) were revealed at the end of treatment in the main group compared to the control group. We observed an improvement in distance walked (p=0.01) and the values SpO2 (p=0.04) in 6-minute walk test, the increase in the volumetric blood flow velocity in venules (p<0.001), and the date in oxidative damage (p<0.001) and antioxidant activity (p=0.03) parameters in the blood serum. CONCLUSION: The results of the study demonstrate clinical efficacy iNO/iH2 on clinical indicators, parameters of oxidative stress and microcirculation in patients with PS.", "conclusion": "The results of the study demonstrate clinical efficacy iNO/iH2 on clinical indicators, parameters of oxidative stress and microcirculation in patients with PS." }, { "pmid": "38794767", "year": 2024, "title": "The Effect of 14-Day Consumption of Hydrogen-Rich Water Alleviates Fatigue but Does Not Ameliorate Dyspnea in Long-COVID Patients: A Pilot, Single-Blind, and Randomized, Controlled Trial", "title_en": null, "title_de": "Der 14-tägige Konsum von wasserstoffreichem Wasser lindert Müdigkeit, bessert jedoch nicht die Atemnot bei Long-COVID-Patienten: eine einfach-verblindete, randomisierte, kontrollierte Pilotstudie", "journal": "Nutrients", "authors": "Tan et al.", "author_search": "tan tan", "doi": "10.3390/nu16101529", "doi_url": "https://doi.org/10.3390/nu16101529", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38794767/", "url": "https://h2medicine.org/studies/study-tan-2024-long-covid-fatigue-dyspnea/", "methods": [ "drinking-hrw" ], "indications": [ "respiratory", "immune-system", "sports-exercise" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2024 · Tan — The Effect of 14-Day Consumption of Hydrogen-Rich Water Alleviates Fatigue but Does Not Ameliorate Dyspnea in Long-COVID Patients: A Pilot, Single-Blind, and Randomized, Controlled Trial", "summary": "Hydrogen-rich water alleviates exhaustion in Long-COVID — but not shortness of breath. In a 14-day randomized pilot trial (n = 32), H₂ water lowered fatigue, increased the distance in the 6-minute walk test, and markedly improved leg strength and sleep quality; shortness of breath, however, did not improve. (Nutrients, 2024.)", "assessment": "Relevant for H₂ water applications in the context of exhaustion, recovery and post-infection convalescence — a big topic since the pandemic. A strength is the honest, differentiated reporting: an effect where it is measurable (fatigue, endurance, sleep), no whitewashing on shortness of breath. The reported effect sizes (Cohen's d up to 1.27) are notable. Limitation, stated honestly: declared as a pilot study, a small sample (n = 32 of 55), only single-blind (not double-blind) — therefore classified as a pilot/near-open-label design. Subjective endpoints like fatigue are more susceptible to expectation effects when blinding is only single.", "abstract": "(1) Background: Hydrogen (H2) may be a potential therapeutic agent for managing Long COVID symptoms due to its antioxidant and anti-inflammatory properties. However, more scientific literature is needed to describe the effects of H2 administration on treating symptoms. A study aimed to investigate the impact of hydrogen-rich water (HRW) administration on the fatigue and dyspnea of Long-COVID patients for 14 consecutive days. (2) Methods: In this randomized, single-blind, placebo-controlled study, 55 participants were recruited, and 23 of them were excluded. A total of 32 eligible participants were randomized into a hydrogen-rich water (HRW) group (n = 16) and a placebo water (PW) group (n = 16) in which they were instructed to consume hydrogen-rich water or placebo water for 14 days, respectively. The participants completed the Fatigue Severity Scale (FSS), Six-Minute Walk Test (6MWT), 30 s Chair Stand Test (30s-CST), Modified Medical Research Council Dyspnea Rating Scale (mMRC), Pittsburgh Sleep Quality Index (PSQI), and depression anxiety stress scale (DASS-21) before and after the intervention. A linear mixed-effects model was used to analyze the effects of HRW. Cohen's d values were used to assess the effect size when significance was observed. The mean change with 95% confidence intervals (95% CI) was also reported. (3) Results: The effects of HRW on lowering FSS scores (p = 0.046, [95% CI = -20.607, -0.198, d = 0.696] and improving total distance in the 6WMT (p < 0.001, [95% CI = 41.972, 61.891], d = 1.010), total time for the 30s-CST (p = 0.002, [95% CI = 1.570, 6.314], d = 1.190), and PSQI scores (p = 0.012, [95% CI = -5.169, 0.742], d = 1.274) compared to PW were of a significantly moderate effect size, while there was no significant difference in mMRC score (p = 0.556) or DASS-21 score (p > 0.143). (4) Conclusions: This study demonstrates that HRW might be an effective strategy for alleviating fatigue and improving cardiorespiratory endurance, musculoskeletal function, and sleep quality. Still, it does not ameliorate dyspnea among Long-COVID patients.", "conclusion": "This study demonstrates that HRW might be an effective strategy for alleviating fatigue and improving cardiorespiratory endurance, musculoskeletal function, and sleep quality. Still, it does not ameliorate dyspnea among Long-COVID patients." }, { "pmid": "39016593", "year": 2024, "title": "H2 inhalation therapy in patients with moderate COVID-19 (H2COVID): a prospective ascending-dose phase I clinical trial.", "title_en": null, "title_de": "H2-Inhalationstherapie bei Patienten mit moderatem COVID-19 (H2COVID): eine prospektive Phase-I-Studie mit ansteigender Dosis", "journal": "Antimicrobial Agents and Chemotherapy", "authors": "Salomez-Ihl et al.", "author_search": "salomez-ihl salomez-ihl", "doi": "10.1128/aac.00573-24", "doi_url": "https://doi.org/10.1128/aac.00573-24", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39016593/", "url": "https://h2medicine.org/studies/study-salomez-ihl-2024-h2covid-phase-i-moderate-covid-19/", "methods": [ "inhalation", "bath-topical" ], "indications": [ "respiratory", "immune-system", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2024 · Salomez-Ihl — H2 inhalation therapy in patients with moderate COVID-19 (H2COVID): a prospective ascending-dose phase I clinical trial", "summary": "Inhaling hydrogen is safe and well tolerated in COVID-19 patients. The first phase-I study (n = 12) showed: a mixture of 3.6% H₂ and 96.4% N₂ was tolerated over up to at least 3 days without explosion risk — every patient improved clinically. (Antimicrobial Agents and Chemotherapy, 2024.)", "assessment": "Valuable as safety evidence for H₂ inhalation in a clinical setting — an argument that counts in any serious information on hydrogen applications. The study shows that H₂ inhalation is well tolerated even in the acutely ill and can be implemented technically safely (no explosion risk). Limitation, stated honestly: it is explicitly a phase-I safety study with only 12 patients and no control group — the „clinical improvement“ here is not proof of efficacy, but an observation that can be explained by the natural course of the disease. Efficacy must yet be demonstrated in larger controlled studies.", "abstract": "UNLABELLED: The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has triggered a serious global health crisis, resulting in millions of reported deaths since its initial identification in China in November 2019. The global disparities in immunization access emphasize the urgent need for ongoing research into therapeutic interventions. This study focuses on the potential use of molecular dihydrogen (H2) inhalation as an adjunctive treatment for COVID-19. H2 therapy shows promise in inhibiting intracellular signaling pathways associated with inflammation, particularly when administered early in conjunction with nasal oxygen therapy. This phase I study, characterized by an open-label, prospective, monocentric, and single ascending-dose design, seeks to assess the safety and tolerability of the procedure in individuals with confirmed SARS-CoV-2 infection. Employing a 3 + 3 design, the study includes three exposure durations (target durations): 1 day (D1), 3 days (D2), and 6 days (D3). We concluded that the maximum tolerated duration is at least 3 days. Every patient showed clinical improvement and excellent tolerance to H2 therapy. To the best of our knowledge, this phase I clinical trial is the first to establish the safety of inhaling a mixture of H2 (3.6%) and N2 (96.4%) in hospitalized COVID-19 patients. The original device and method employed ensure the absence of explosion risk. The encouraging outcomes observed in the 12 patients included in the study justify further exploration through larger, controlled clinical trials. CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT04633980.", "conclusion": "The encouraging outcomes observed in the 12 patients included in the study justify further exploration through larger, controlled clinical trials. CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT04633980." }, { "pmid": "39133068", "year": 2024, "title": "Combination of Hydrogen Inhalation and Hypothermic Temperature Control After Out-of-Hospital Cardiac Arrest: A Post hoc Analysis of the Efficacy of Inhaled Hydrogen on Neurologic Outcome Following Brain Ischemia During PostCardiac Arrest Care II Trial", "title_en": null, "title_de": "Kombination aus Wasserstoff-Inhalation und hypothermer Temperaturkontrolle nach außerklinischem Herzstillstand: eine Post-hoc-Analyse der HYBRID-II-Studie zur Wirksamkeit inhalierten Wasserstoffs auf das neurologische Ergebnis nach zerebraler Ischämie", "journal": "Critical Care Medicine", "authors": "Tamura et al.", "author_search": "tamura tamura", "doi": "10.1097/ccm.0000000000006395", "doi_url": "https://doi.org/10.1097/ccm.0000000000006395", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39133068/", "url": "https://h2medicine.org/studies/study-tamura-2024-cardiac-arrest-hypothermic-neurologic-outcome/", "methods": [ "inhalation" ], "indications": [ "neurology", "cardiovascular" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2024 · Tamura — Combination of Hydrogen Inhalation and Hypothermic Temperature Control After Out-of-Hospital Cardiac Arrest: A Post hoc Analysis of the Efficacy of Inhaled Hydrogen on Neurologic Outcome Following Brain Ischemia During PostCardiac Arrest Care II Trial", "summary": "Hydrogen inhalation plus deep cooling improves the neurologic outcome after cardiac arrest. In the post-hoc analysis of the HYBRID-II trial, 68% achieved a good neurologic outcome under hydrogen + hypothermia (32–34 °C) vs. 38% under cooling alone (relative risk 1.81). (Critical Care Medicine, 2024 — exploratory secondary analysis, n = 72.)", "assessment": "Relevant for H₂ inhalation applications in the high-risk medical domain, because a hard neurologic endpoint is examined here in a renowned intensive-care journal (Critical Care Medicine) — and the data come from a real randomized trial. Limitation, stated honestly and prominently: it is a post-hoc subgroup analysis, not a pre-specified RCT endpoint. The case number is small (n = 72), the confidence interval of the adjusted odds ratio (1.88–138.17) is so wide that the effect size is practically undetermined, and survival was not improved. Such findings are hypothesis-generating and must be confirmed in a dedicated, adequately powered study.", "abstract": "The Efficacy of Inhaled Hydrogen on Neurologic Outcome Following Brain Ischemia During Post-Cardiac Arrest Care (HYBRID) II trial (jRCTs031180352) suggested that hydrogen inhalation may reduce post-cardiac arrest brain injury (PCABI). However, the combination of hypothermic target temperature management (TTM) and hydrogen inhalation on outcomes is unclear. The aim of this study was to investigate the combined effect of hydrogen inhalation and hypothermic TTM on outcomes after out-of-hospital cardiac arrest (OHCA). Post hoc analysis of a multicenter, randomized, controlled trial. Fifteen Japanese ICUs. Cardiogenic OHCA enrolled in the HYBRID II trial. Hydrogen mixed oxygen (hydrogen group) versus oxygen alone (control group). TTM was performed at a target temperature of 32-34°C (TTM32-TTM34) or 35-36°C (TTM35-TTM36) per the institutional protocol. The association between hydrogen + TTM32-TTM34 and 90-day good neurologic outcomes was analyzed using generalized estimating equations. The 90-day survival was compared between the hydrogen and control groups under TTM32-TTM34 and TTM35-TTM36, respectively. The analysis included 72 patients (hydrogen [ n = 39] and control [ n = 33] groups) with outcome data. TTM32-TTM34 was implemented in 25 (64%) and 24 (73%) patients in the hydrogen and control groups, respectively ( p = 0.46). Under TTM32-TTM34, 17 (68%) and 9 (38%) patients achieved good neurologic outcomes in the hydrogen and control groups, respectively (relative risk: 1.81 [95% CI, 1.05-3.66], p < 0.05). Hydrogen + TTM32-TTM34 was independently associated with good neurologic outcomes (adjusted odds ratio 16.10 [95% CI, 1.88-138.17], p = 0.01). However, hydrogen + TTM32-TTM34 did not improve survival compared with TTM32-TTM34 alone (adjusted hazard ratio: 0.22 [95% CI, 0.05-1.06], p = 0.06). Hydrogen + TTM32-TTM34 was associated with improved neurologic outcomes after cardiogenic OHCA compared with TTM32-TTM34 monotherapy. Hydrogen inhalation is a promising treatment option for reducing PCABI when combined with TTM32-TTM34.", "conclusion": "Hydrogen + TTM32-TTM34 was associated with improved neurologic outcomes after cardiogenic OHCA compared with TTM32-TTM34 monotherapy. Hydrogen inhalation is a promising treatment option for reducing PCABI when combined with TTM32-TTM34." }, { "pmid": "39310256", "year": 2024, "title": "Using oral molecular hydrogen supplements to combat microinflammation in humans: a pilot observational study.", "title_en": null, "title_de": "Einsatz oraler molekularer Wasserstoff-Präparate zur Bekämpfung von Mikroinflammation beim Menschen: eine Pilot-Beobachtungsstudie", "journal": "International Journal of Medical Sciences", "authors": "Lu et al.", "author_search": "lu lu", "doi": "10.7150/ijms.101114", "doi_url": "https://doi.org/10.7150/ijms.101114", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39310256/", "url": "https://h2medicine.org/studies/study-lu-2024-oral-supplements-microinflammation/", "methods": [ "drinking-hrw" ], "indications": [ "immune-system", "oxidative-stress", "metabolic" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2024 · Lu — Using oral molecular hydrogen supplements to combat microinflammation in humans: a pilot observational study", "summary": "Solid oral hydrogen capsules lowered inflammation markers in chronically ill patients. In a pilot study (n = 30) over 4 weeks, the erythrocyte sedimentation rate (ESR) fell dose-dependently (high dose p = 0.016) and the inflammation score DAS28 fell significantly; CRP showed a decreasing trend. (Int. J. Medical Sciences, 2024.)", "assessment": "Relevant because an alternative H₂ delivery (solid capsules with delayed release) is tested here in humans — a concept beyond H₂ water and inhalation that is interesting for application development. The anti-inflammatory direction fits the selective antioxidant profile of H₂ well mechanistically (see Ohsawa 2007). Limitation, stated honestly: a very small sample (n = 30, 10 per dose group), a pilot/observational design without placebo blinding, a mixed patient cohort, and the most important inflammation marker CRP remained only a trend (p = 0.077). This is a promising signal, not proof of efficacy.", "abstract": "Background: Persistent inflammation over time can cause gradual harm to the body. Molecular hydrogen has the potential to specifically counteract reactive oxygen species (ROS), reduce disease severity, and enhance overall health. Investigations of the anti-inflammatory and antioxidant properties of oral solid hydrogen capsules (OSHCs) are currently limited, prompting our examination of the beneficial effects of OSHCs. Subsequently, we conducted a clinical study to assess the impact of OSHCs supplementation on individuals with chronic inflammation. Materials and methods: Initially, we evaluated the oxidative reduction potential (ORP) properties of the OSHCs solution by comparing it to hydrogen-rich water (HRW) and calcium hydride (CaH2) treated water. In our outpatient department, stable patients with chronic illnesses who were treated with varying doses of OSHCs were randomized into low-, medium-, and high-dose groups for 4 weeks. Primary outcomes included changes in the serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) concentrations after four weeks of OSHCs consumption. Secondary outcomes included changes in the Brief Fatigue Inventory-Taiwan (BFI-T) fatigue scale, Control Status Scale for Diabetes (CSSD70) scores, and Disease Activity Score 28 (DAS28). Results: Compared to HRW and CaH2, OSHCs demonstrated a prolonged reduction in ORP for 60 minutes in vitro and enabled a regulated release of hydrogen over 24 hours. A total of 30 participants, with 10 in each dosage (low/medium/high) group, completed the study. The average ESR120 significantly decreased from the first week to the fourth week, with a noticeable dose effect (low-dose group, p = 0.494; high-dose group, p = 0.016). Overall, the average CRP concentration showed a distinct decreasing trend after four weeks of OSHCs administration (w0 vs. w4, p = 0.077). The average DAS28 score demonstrated a significant decrease following OSHCs treatment. Furthermore, there were improvements in the BFI-T and CSSD70 scores. Conclusion: OSHCs supplementation may exert anti-inflammatory and antioxidant effects on individuals with chronic inflammation. However, further clinical studies could be investigated to explore the potential therapeutic effects of OSHCs.", "conclusion": "OSHCs supplementation may exert anti-inflammatory and antioxidant effects on individuals with chronic inflammation. However, further clinical studies could be investigated to explore the potential therapeutic effects of OSHCs." }, { "pmid": "39477420", "year": 2024, "title": "Molecular Hydrogen Therapy in Aneurysmal SAH With RA and Newly-diagnosed SLE, Complicated With Acute Ischemic Infarction: A Case Report of Improved Immune Markers Including Tr1 Cells, Breg Cells and TIM3 Expression on Tc Cells.", "title_en": null, "title_de": "Molekulare Wasserstofftherapie bei aneurysmatischer SAB mit RA und neu diagnostiziertem SLE, kompliziert durch akuten ischämischen Infarkt: Ein Fallbericht über verbesserte Immunmarker einschließlich Tr1-Zellen, Breg-Zellen und TIM3-Expression auf Tc-Zellen.", "journal": "In vivo (Athens, Greece)", "authors": "Chen et al.", "author_search": "chen chen", "doi": "10.21873/invivo.13799", "doi_url": "https://doi.org/10.21873/invivo.13799", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39477420/", "url": "https://h2medicine.org/studies/study-chen-2024-aneurysmal-sah-newly-diagnosed/", "methods": [ "drinking-hrw" ], "indications": [ "neurology", "skin-aging", "joints-rheumatology", "immune-system" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2024 · Chen — Molecular Hydrogen Therapy in Aneurysmal SAH With RA and Newly-diagnosed SLE, Complicated With Acute Ischemic Infarction: A Case Report of Improved Immune Markers Including Tr1 Cells, Breg Cells and TIM3 Expression on Tc Cells.", "summary": "A 44-year-old woman with a ruptured brain aneurysm, rheumatoid arthritis, and newly diagnosed lupus remained unconscious despite surgery, immunosuppressants, and plasmapheresis — until daily hydrogen capsules were added. After starting H₂ therapy, key immune markers normalised (Treg and Breg cells rose, anti-dsDNA turned negative), and her clinical status stabilised. (In Vivo, 2024.)", "assessment": "A hypothesis-generating case report from a highly unusual combination of diagnoses. The immune phenotype data is specific and measurable, lending some biological credibility, but no causal conclusion can be drawn from a single case. Confounders abound: ongoing immunosuppressants, plasmapheresis, natural disease trajectory, and regression to the mean. Limitations: n=1; no control; concurrent intensive therapy; no washout; unclear H₂ dose and duration before stabilisation. Should be read as a signal, not a finding.", "abstract": "BACKGROUND/AIM: Most nontraumatic subarachnoid hemorrhages (SAHs) are caused by ruptured saccular aneurysms, often resulting in a devastating clinical event characterized by high mortality and significant morbidity among survivors. Numerous studies have confirmed the neuroprotective effects of the molecular hydrogen due to its unique biological properties. CASE REPORT: We present the case of a 44-year-old female with aneurysmal SAH with rheumatoid arthritis (RA) and newly diagnosed systemic lupus erythematosus (SLE), complicated by acute ischemic infarction. Despite surgical, pharmacological and non-pharmacological interventions, including embolization of the aneurysm, immunosuppressant, non-vitamin K antagonist oral anticoagulant (NOAC), and plasmapheresis, loss of consciousness continued. The patient began daily treatment with hydrogen capsules, resulting in increased in Treg cells, Breg cells, increased TIM3+ expression on Tc cells, and the conversion of anti-dsDNA from positive to negative. Her clinical symptoms stabilized without adverse effects. CONCLUSION: This case highlights the potential benefits of molecular hydrogen therapy in managing aneurysmal SAH with underlying autoimmune disease, warranting further research.", "conclusion": "This case highlights the potential benefits of molecular hydrogen therapy in managing aneurysmal SAH with underlying autoimmune disease, warranting further research." }, { "pmid": "39477378", "year": 2024, "title": "Molecular Hydrogen Therapy in Sjögren's Syndrome With Pulmonary Arterial Hypertension and Right-sided Heart Failure: A Case Report of Improved Immune Markers Including Treg, B Cells and Plasma Cell.", "title_en": null, "title_de": "Molekulare Wasserstofftherapie beim Sjögren-Syndrom mit pulmonaler arterieller Hypertonie und Rechtsherzinsuffizienz: Ein Fallbericht über verbesserte Immunmarker einschließlich Treg, B-Zellen und Plasmazellen.", "journal": "In vivo (Athens, Greece)", "authors": "Lin et al.", "author_search": "lin lin", "doi": "10.21873/invivo.13797", "doi_url": "https://doi.org/10.21873/invivo.13797", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39477378/", "url": "https://h2medicine.org/studies/study-lin-2024-sjoegren-syndrome-pulmonary-arterial/", "methods": [ "unspecified" ], "indications": [ "cardiovascular", "respiratory", "skin-aging", "immune-system" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2024 · Lin — Molecular Hydrogen Therapy in Sjögren's Syndrome With Pulmonary Arterial Hypertension and Right-sided Heart Failure: A Case Report of Improved Immune Markers Including Treg, B Cells and Plasma Cell.", "summary": "A 56-year-old woman with Sjögren's syndrome-associated pulmonary arterial hypertension and right-sided heart failure — unresponsive to five standard drugs — experienced clinical stabilisation and measurable immune improvement after starting daily hydrogen capsules as an add-on. Treg cells rose, anti-Ro antibodies fell, and B cell subsets decreased. (In Vivo, 2024.)", "assessment": "A rare and difficult-to-study disease context makes this case clinically interesting but causally inconclusive. The immune marker specificity (CD127+ Treg, anti-Ro, B cell subsets) adds biological plausibility. Limitations: n=1; 10-year disease history with prior multiple drug failures means the baseline is highly unstable; no control arm; concurrent standard therapy continued unchanged; no stated H₂ dose. The safety observation (no adverse effects) is consistent with H₂'s known tolerability profile. Should be read as a hypothesis-generating signal only.", "abstract": "BACKGROUND/AIM: Connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) is a severe complication characterized by elevated pulmonary artery pressure, which can lead to right heart failure and death, if untreated. Standard treatments often fail to adequately manage symptoms, highlighting the need for novel therapeutic approaches. This study investigated the efficacy of molecular hydrogen (H2) therapy in a patient with CTD-PAH. CASE REPORT: We present the case of a 56-year-old female with CTD-PAH, diagnosed in 2013 with Sjogren's syndrome complicated by interstitial lung disease (ILD) and PAH. Despite treatment with sildenafil, bosentan, macitentan, iloprost, and corticosteroids, her condition deteriorated, resulting in severe dyspnea and cardiogenic shock in 2020. In May 2023, molecular hydrogen therapy was initiated as an adjuvant treatment. The patient received daily hydrogen capsules, which led to increased CD127+ Treg cells, reduced anti-Ro antibodies, and decreased B cell subsets. Her clinical symptoms stabilized without adverse effects. CONCLUSION: This case highlights the potential benefits of molecular hydrogen therapy in CTD-PAH. H2 therapy exhibiting anti-inflammatory and immunomodulatory effects, leading to improved immune cell profiles and stabilizing clinical symptoms in a patient unresponsive to conventional treatments. Further research is needed to elucidate the mechanisms of H2 therapy and validate its efficacy in larger cohorts. Molecular hydrogen therapy shows promise as a safe adjunctive treatment for CTD-PAH, offering a new approach for managing this challenging condition.", "conclusion": "This case highlights the potential benefits of molecular hydrogen therapy in CTD-PAH. H2 therapy exhibiting anti-inflammatory and immunomodulatory effects, leading to improved immune cell profiles and stabilizing clinical symptoms in a patient unresponsive to conventional treatments. Further research is needed to elucidate the mechanisms of H2 therapy and validate its efficacy in larger cohorts. Molecular hydrogen therapy shows promise as a safe adjunctive treatment for CTD-PAH, offering a new a" }, { "pmid": "39400361", "year": 2024, "title": "Modulating the Electronic Structure of MnNi2S3 Nanoelectrodes to Activate Pyroptosis for Electrocatalytic Hydrogen-Immunotherapy.", "title_en": null, "title_de": "Modulation der elektronischen Struktur von MnNi₂S₃-Nanoelektroden zur Aktivierung der Pyroptose für die elektrokatalytische Wasserstoff-Immuntherapie.", "journal": "Advanced materials (Deerfield Beach, Fla.)", "authors": "Li et al.", "author_search": "li li", "doi": "10.1002/adma.202412925", "doi_url": "https://doi.org/10.1002/adma.202412925", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39400361/", "url": "https://h2medicine.org/studies/study-li-2024-modulating-electronic-structure-mnni2s3/", "methods": [ "unspecified" ], "indications": [ "liver", "cancer", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2024 · Li — Modulating the Electronic Structure of MnNi₂S₃ Nanoelectrodes to Activate Pyroptosis for Electrocatalytic Hydrogen-Immunotherapy.", "summary": "Specially engineered nanoelectrodes deliver molecular hydrogen directly to tumor cells via electrolysis, triggering a cell-death pathway called pyroptosis that also activates the immune system to fight cancer. In this cell-culture study, the approach both killed tumor cells and turned immunologically „cold“ tumors into „hot“ ones capable of eliciting an immune response. (Advanced Materials, 2024.)", "assessment": "This is an in-vitro/preclinical study — all results come from cell cultures and animal tumor models. The findings are mechanistically interesting and technically sophisticated, but cannot be transferred to humans without clinical trials. The concept of electrocatalytic H₂ delivery as a cancer therapy is at a very early stage. No safety, tolerability, or efficacy data in humans exist. The paper should be understood as exploratory materials science and cell biology, not as evidence for human cancer treatment.", "abstract": "Hydrogen (H2) therapy has demonstrated antitumor effect, but the therapeutic efficacy is restricted by the low solubility and nontarget delivery of H2. Electrolysis of H2O by electrocatalysts sustainably releases enormous amounts of H2 and inspires the precise delivery of H2 for tumor therapy. Herein, manganese-doped Ni2S3 nanoelectrodes (MnNi2S3 NEs) are designed for the electrocatalytic delivery of H2 and the activation of antitumor immunity to effectively potentiate H2-immunotherapy. Ni atoms featuring empty 3d orbitals reduce the initial energy barrier of the hydrogen evolution reaction (HER) by promoting the adsorption of H2O. Moreover, Mn atoms with different electronegativity modulate the electronic structure of Ni atoms and facilitate the desorption of the generated H2, thus enhancing the HER activity of the MnNi2S3 NEs. Based on the high HER activity, controllable delivery of H2 for electrocatalytic hydrogen therapy (EHT) is achieved in a voltage-dependent manner. Mechanistically, MnNi2S3 NE-mediated EHT induces mitochondrial dysfunction and oxidative stress, which subsequently activates pyroptosis through the typical ROS/caspase-1/GSDMD signaling pathway. Furthermore, MnNi2S3 NE-mediated EHT enhances the infiltration of CD8+ T lymphocytes into tumors and reverses the immunosuppressive microenvironment. This work demonstrates an electrocatalyst with high HER activity for synergistic gas-immunotherapy, which may spark electrocatalyst-based tumor therapy strategies.", "conclusion": "Furthermore, MnNi2S3 NE-mediated EHT enhances the infiltration of CD8+ T lymphocytes into tumors and reverses the immunosuppressive microenvironment. This work demonstrates an electrocatalyst with high HER activity for synergistic gas-immunotherapy, which may spark electrocatalyst-based tumor therapy strategies." }, { "pmid": "39271809", "year": 2024, "title": "The effect of hydrogen gas on the oxidative stress response in adipose tissue.", "title_en": null, "title_de": "Die Wirkung von Wasserstoffgas auf die Reaktion auf oxidativen Stress im Fettgewebe.", "journal": "Scientific reports", "authors": "Tumurbaatar et al.", "author_search": "tumurbaatar tumurbaatar", "doi": "10.1038/s41598-024-72626-2", "doi_url": "https://doi.org/10.1038/s41598-024-72626-2", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39271809/", "url": "https://h2medicine.org/studies/study-tumurbaatar-2024-oxidative-stress-response-adipose/", "methods": [ "inhalation" ], "indications": [ "metabolic", "cardiovascular", "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2024 · Tumurbaatar — The effect of hydrogen gas on the oxidative stress response in adipose tissue.", "summary": "Human fat tissue soaked in hydrogen-dissolved culture medium showed reduced markers of harmful oxidative stress and a trend toward smaller fat cell size. This ex-vivo tissue study on samples from cardiac surgery patients found changes in key antioxidant proteins and in gene expression of adipocytokines related to fat metabolism. (Scientific Reports, 2024.)", "assessment": "This is a small ex-vivo human tissue study (n=12) — human fat samples treated outside the body with hydrogen-saturated medium. While the use of actual human tissue is a strength compared to animal or cell-line models, the ex-vivo setting means results cannot be directly translated to effects in living humans. The sample size is very small, several key results did not reach statistical significance, and there is no control over H₂ concentration or dose. The study is hypothesis-generating, not confirmatory. No clinical conclusions about treating obesity, metabolic disease, or atherosclerosis should be drawn from this data alone.", "abstract": "Oxidative stress in adipose tissue may alter the secretion pattern of adipocytokines and potentially promote atherosclerosis. However, the therapeutic role of hydrogen in adipose tissue under oxidative stress remains unclear. In this study, subcutaneous adipose tissue (SCAT) was collected from the mid-thoracic wounds of 12 patients who underwent open-heart surgery with a mid-thoracic incision. The adipose tissue was then immersed in a culture medium dissolved with hydrogen, which was generated using a hydrogen-generating device. The weight of the adipose tissue was measured before and after hydrogenation, and the tissue was immunostained for nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and superoxide dismutase (SOD), which are markers of oxidative stress. The immunostaining results showed that HO-1 and Nrf2 expression levels were significantly decreased in the hydrogenated group, whereas SOD expression levels increased, but did not attain statistical significance. Image analysis of adipose tissue revealed that a reduction in adipocyte size. Furthermore, hydrogenated adipose tissue showed a trend toward increased gene expression levels of adiponectin and decreased gene expression levels of chemerin, an adipocytokine involved in adipogenesis. These results demonstrated the therapeutic potential of hydrogen gas for oxidative stress in adipose tissue and for reducing adipocyte size.", "conclusion": "Furthermore, hydrogenated adipose tissue showed a trend toward increased gene expression levels of adiponectin and decreased gene expression levels of chemerin, an adipocytokine involved in adipogenesis. These results demonstrated the therapeutic potential of hydrogen gas for oxidative stress in adipose tissue and for reducing adipocyte size." }, { "pmid": "39216558", "year": 2024, "title": "Hydrogen regulated pyroptosis through NLRP3-GSDMD pathway to improve airway mucosal oxidative stress injury induced by endotracheal tube cuff compression.", "title_en": null, "title_de": "Wasserstoff reguliert die Pyroptose über den NLRP3-GSDMD-Signalweg zur Verbesserung der durch Endotrachealtubus-Cuff-Kompression induzierten oxidativen Stressschädigung der Atemwegsschleimhaut.", "journal": "Free radical biology & medicine", "authors": "Mu et al.", "author_search": "mu mu", "doi": "10.1016/j.freeradbiomed.2024.08.035", "doi_url": "https://doi.org/10.1016/j.freeradbiomed.2024.08.035", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39216558/", "url": "https://h2medicine.org/studies/study-mu-2024-regulated-pyroptosis-through-nlrp3/", "methods": [ "inhalation", "saline-iv" ], "indications": [ "respiratory", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2024 · Mu — Hydrogen regulated pyroptosis through NLRP3-GSDMD pathway to improve airway mucosal oxidative stress injury induced by endotracheal tube cuff compression.", "summary": "Endotracheal tube cuffs compress airway tissue during anaesthesia, triggering oxidative stress and a form of inflammatory cell death (pyroptosis) — and hydrogen inhalation or hydrogen-rich saline in the cuff significantly reduced this damage. In patients under general anaesthesia, filling the cuff with hydrogen-rich saline cut postoperative sore throat rates markedly. (Free Radical Biology and Medicine, 2024.)", "assessment": "One of the more clinically concrete H₂ papers: laboratory mechanisms are tied to a directly measurable, patient-relevant outcome (postoperative sore throat). The NLRP3-GSDMD pathway is a well-established inflammation cascade, and H₂'s inhibition of it is mechanistically coherent. Limitations: the clinical arm's sample size is not reported in the abstract; the postoperative sore throat endpoint, while patient-relevant, is soft (subjective); the mechanism was established in cellular models first, with clinical data following — the sequence is logical but the clinical sample needs scrutiny. The cuff-saline modification would require formal clinical trial data before adoption in anaesthesia practice.", "abstract": "The cuff of endotracheal tube (ETT) is an indispensable device for establishing an artificial airway, yet cuff-induced compression often causes damage to the airway mucosa. The mechanism of this damage involves mucosal compression ischemia and the oxidative stress injury following reperfusion. Currently, there is a lack of effective strategies to protect the mucosa. Hydrogen, as a natural antioxidant, has demonstrated significant potential in the prevention and treatment of oxidative stress injuries. This study aimed to determine the protective effects of hydrogen on compressed airway mucosa. We found that the damage to the airway mucosa caused by ETT cuff compression was associated with oxidative stress-induced pyroptosis of airway epithelial cells. Inhalation of hydrogen effectively reduced the levels of reactive oxygen species, significantly ameliorating changes in epithelial cell pyroptosis, and this protective effect is linked to the inhibition of the NLRP3-GSDMD pathway. Further cellular studies, involving knockdown and overexpression of NLRP3, clarified that hydrogen exerts its protective effects on the airway mucosa by inhibiting epithelial cell pyroptosis. Additionally, we observed that using hydrogen-rich saline to inflate the ETT cuff in patients under general anesthesia significantly reduced postoperative sore throat. This study confirms that hydrogen effectively enhances tolerance of airway mucosa to oxidative stress injuries, offering a potential preventive and therapeutic strategy for protecting the airway mucosa in patients undergoing endotracheal intubation.", "conclusion": "Additionally, we observed that using hydrogen-rich saline to inflate the ETT cuff in patients under general anesthesia significantly reduced postoperative sore throat. This study confirms that hydrogen effectively enhances tolerance of airway mucosa to oxidative stress injuries, offering a potential preventive and therapeutic strategy for protecting the airway mucosa in patients undergoing endotra" }, { "pmid": "39173802", "year": 2024, "title": "Multifaceted exploration of acylthiourea compounds: In vitro cytotoxicity, DFT calculations, molecular docking and dynamics simulation studies.", "title_en": null, "title_de": "Vielschichtige Untersuchung von Acylthioharnstoff-Verbindungen: In-vitro-Zytotoxizität, DFT-Berechnungen, molekulares Docking und Dynamiksimulationsstudien.", "journal": "International journal of biological macromolecules", "authors": "Haribabu et al.", "author_search": "haribabu haribabu", "doi": "10.1016/j.ijbiomac.2024.134870", "doi_url": "https://doi.org/10.1016/j.ijbiomac.2024.134870", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39173802/", "url": "https://h2medicine.org/studies/study-haribabu-2024-multifaceted-exploration-acylthiourea-compounds/", "methods": [ "unspecified" ], "indications": [ "respiratory" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2024 · Haribabu — Multifaceted exploration of acylthiourea compounds: In vitro cytotoxicity, DFT calculations, molecular docking and dynamics simulation studies.", "summary": "Two newly synthesized acylthiourea compounds were characterized and tested for cytotoxicity against cancer cells, with molecular docking suggesting potential binding to viral proteases. The study uses computational methods alongside laboratory synthesis — molecular hydrogen (H₂) appears only as a structural element in intermolecular hydrogen bonds, not as a therapeutic agent. (International Journal of Biological Macromolecules, 2024.)", "assessment": "This is an in-vitro and computational study on newly synthesized chemical compounds — it is not a study on molecular hydrogen (H₂) therapy. The term „hydrogen“ in this paper refers to hydrogen bonds in structural chemistry. No dissolved H₂ gas, H₂-rich water, or H₂ inhalation is studied. Inclusion in the H₂ database appears to be a classification edge case. The cytotoxicity and docking data are preliminary and in silico; no animal or human data are presented. Results should not be cited as evidence for H₂ therapy.", "abstract": "This study reports the synthesis and analysis of biologically active acylthiourea compounds (1 and 2) with a cyclohexyl moiety. The compounds were characterized using UV-Visible, FT-IR, 1H/13C NMR, and elemental analysis. The crystal structure of 2 was solved, revealing intra- and inter-molecular hydrogen bonds. Density functional theory (DFT) calculations provided insights into chemical reactivity and non-covalent interactions. Cytotoxicity assays showed the cyclohexyl group enhanced the activity of compound 2 compared to compound 1. Epoxide hydrolase 1 was predicted as the enzyme target for both compounds. We modeled the structure of epoxide hydrolase 1 and performed molecular dynamics simulation and docking studies. Additionally, in silico docking with SARS-CoV-2 main protease, human ACE2, and avian influenza H5N1 hemagglutinin indicated strong binding potential of the compounds. This integrated approach improves our understanding of the biological potential of acylthiourea derivatives.", "conclusion": "Additionally, in silico docking with SARS-CoV-2 main protease, human ACE2, and avian influenza H5N1 hemagglutinin indicated strong binding potential of the compounds. This integrated approach improves our understanding of the biological potential of acylthiourea derivatives." }, { "pmid": "39147072", "year": 2024, "title": "Hydrogen-rich water alleviates asthma airway inflammation by modulating tryptophan metabolism and activating aryl hydrocarbon receptor via gut microbiota regulation.", "title_en": null, "title_de": "Wasserstoffreiches Wasser lindert die Atemwegsentzündung bei Asthma durch Modulation des Tryptophan-Stoffwechsels und Aktivierung des Aryl-Hydrocarbon-Rezeptors über die Regulation der Darmmikrobiota.", "journal": "Free radical biology & medicine", "authors": "Li et al.", "author_search": "li li", "doi": "10.1016/j.freeradbiomed.2024.08.009", "doi_url": "https://doi.org/10.1016/j.freeradbiomed.2024.08.009", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39147072/", "url": "https://h2medicine.org/studies/study-li-2024-alleviates-asthma-airway-inflammation/", "methods": [ "drinking-hrw" ], "indications": [ "respiratory", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2024 · Li — Hydrogen-rich water alleviates asthma airway inflammation by modulating tryptophan metabolism and activating aryl hydrocarbon receptor via gut microbiota regulation.", "summary": "In asthmatic mice, hydrogen-rich water (HRW) shifted gut bacteria toward beneficial species and raised levels of a key bacterial metabolite that calmed airway inflammation via a specific receptor pathway. Both lab experiments and cell studies suggested HRW's anti-asthma effects work partly through the gut-lung axis. (Free Radical Biology & Medicine, 2024.)", "assessment": "This is an animal study (mouse model of asthma). The findings are scientifically interesting — the proposed gut-lung axis mechanism is plausible and the microbiome + metabolomics evidence is detailed. However, results from asthmatic mice cannot be directly applied to human asthma patients. Mouse asthma models differ substantially from human asthma in their immunology and microbiome composition. The study demonstrates a plausible biological pathway for HRW effects on the gut-lung axis, but clinical confirmation in humans is required before any therapeutic claims can be made.", "abstract": "Hydrogen-rich water (HRW) is a beverage containing a high concentration of hydrogen that has been researched for its antioxidant, anti-apoptotic, and anti-inflammatory properties in asthma. This study investigates the potential therapeutic impact of HRW on the gut-lung axis. Using 16S rRNA and serum metabolomics, we examined changes in gut microbiota and serum metabolites in asthmatic mice after HRW intervention, followed by validation experiments. The findings revealed that HRW influenced gut microbiota by increasing Ligilactobacillus and Bifidobacterium abundance and enhancing the presence of indole-3-acetic acid (IAA), a microbially derived serum metabolite. Both in vivo and in vitro experiments showed that HRW's protective effects against airway inflammation in asthmatic mice may be linked to the gut microbiota, with IAA potentially playing a role in reducing asthmatic airway inflammation through the aryl hydrocarbon receptors (AhR) signaling pathway. In summary, HRW can modify gut microbiota, increase Bifidobacterium abundance, elevate microbial-derived IAA levels, and activate AhR, which could potentially alleviate inflammation in asthma.", "conclusion": "Both in vivo and in vitro experiments showed that HRW's protective effects against airway inflammation in asthmatic mice may be linked to the gut microbiota, with IAA potentially playing a role in reducing asthmatic airway inflammation through the aryl hydrocarbon receptors (AhR) signaling pathway. In summary, HRW can modify gut microbiota, increase Bifidobacterium abundance, elevate microbial-der" }, { "pmid": "39116782", "year": 2024, "title": "A novel intervention of molecular hydrogen on the unbalance of the gut microbiome in opioid addiction: Experimental and human studies.", "title_en": null, "title_de": "Eine neuartige Intervention mit molekularem Wasserstoff bei der Dysbalance des Darmmikrobioms bei Opioidabhängigkeit: Experimentelle und Humanstudien.", "journal": "Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie", "authors": "Xie et al.", "author_search": "xie xie", "doi": "10.1016/j.biopha.2024.117273", "doi_url": "https://doi.org/10.1016/j.biopha.2024.117273", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39116782/", "url": "https://h2medicine.org/studies/study-xie-2024-intervention-unbalance-gut-microbiome/", "methods": [ "unspecified" ], "indications": [ "metabolic", "neurology" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2024 · Xie — A novel intervention of molecular hydrogen on the unbalance of the gut microbiome in opioid addiction: Experimental and human studies.", "summary": "Molecular hydrogen appears to reduce morphine-seeking behaviour in animal models and, in humans with opioid addiction, improved gut microbiome balance, reduced depression and anxiety symptoms — suggesting a gut-brain axis mechanism. Both animal experiments and a human cohort component were conducted. (Biomedicine and Pharmacotherapy, 2024.)", "assessment": "An intriguing mechanistic hypothesis with solid animal data and an underpowered human component. The SCFA and microbiome sequencing data add specificity to the gut-brain axis claim. Limitations: the human arm's sample size, control conditions, and statistical analysis are not described in the abstract — making the human findings essentially unassessable from available information; conditioned place preference in rodents does not translate directly to human addiction outcomes; H₂ delivery method in humans is not specified. The animal data are internally consistent but preliminary. Needs a properly powered, controlled human trial.", "abstract": "The gut-brain axis mediates the interaction pathway between microbiota and opioid addiction. In recent years, many studies have shown that molecular hydrogen has therapeutic and preventive effects on various diseases. This study aimed to investigate whether molecular hydrogen could serve as pharmacological intervention agent to reduce risks of reinstatement of opioid seeking and explore the mechanism of gut microbiota base on animal experiments and human studies. Morphine-induced conditioned place preference (CPP) was constructed to establish acquisition, extinction, and reinstatement stage, and the potential impact of H2 on the behaviors related to morphine-induced drug extinction was determined using both free accessible and confined CPP extinction paradigms. The effects of morphine on microbial diversity and composition of microbiota, as well as the subsequent changes after H2 intervention, were assessed using 16 S rRNA gene sequencing. Short-Chain Fatty Acids (SCFAs) in mice serum were detected by gas chromatography-mass spectrometry (GC-MS). Meanwhile, we also conducted molecular hydrogen intervention and gut microbiota testing in opioid-addicted individuals. Our results revealed that molecular hydrogen could enhance the extinction of morphine-related behavior, reducing morphine reinstatement. Gut microbes may be a potential mechanism behind the therapeutic effects of molecular hydrogen on morphine addiction. Additionally, molecular hydrogen improved symptoms of depression and anxiety, as well as gut microbial features, in individuals with opioid addiction. This study supports molecular hydrogen as a novel and effective intervention for morphine-induced addiction and reveals the mechanism of gut microbiota.", "conclusion": "Additionally, molecular hydrogen improved symptoms of depression and anxiety, as well as gut microbial features, in individuals with opioid addiction. This study supports molecular hydrogen as a novel and effective intervention for morphine-induced addiction and reveals the mechanism of gut microbiota." }, { "pmid": "39073335", "year": 2024, "title": "Realizing brain therapy with \"smart medicine\": mechanism and case report of molecular hydrogen inhalation for Parkinson's disease.", "title_en": null, "title_de": "Hirntherapie mit „intelligenter Medizin“ verwirklichen: Mechanismus und Fallbericht zur Inhalation von molekularem Wasserstoff bei Parkinson-Krankheit.", "journal": "Medical gas research", "authors": "Ichikawa et al.", "author_search": "ichikawa ichikawa", "doi": "10.4103/2045-9912.385949", "doi_url": "https://doi.org/10.4103/2045-9912.385949", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39073335/", "url": "https://h2medicine.org/studies/study-ichikawa-2024-realizing-brain-smart-medicine/", "methods": [ "inhalation" ], "indications": [ "neurology" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2024 · Ichikawa — Realizing brain therapy with „smart medicine“: mechanism and case report of molecular hydrogen inhalation for Parkinson's disease.", "summary": "A case report describes symptomatic improvement in a Parkinson's disease patient — including reduced body bending and hand tremor — following hydrogen inhalation, alongside a mechanistic argument that H₂ can enter the brain and neutralise the hydroxyl radicals that oxidise dopamine in the midbrain. The authors frame H₂ as a „smart medicine“ that bypasses the barriers blocking conventional central nervous system drugs. (Medical Gas Research, 2024.)", "assessment": "A mechanistically compelling narrative combined with a single case report. The Fenton-reaction / hydroxyl-radical rationale for H₂ in Parkinson's disease is well-established in the laboratory literature and biologically coherent. Limitations: n=1; no control; no standardised rating scales (e.g. UPDRS); no blinding; the paper is partly theoretical/philosophical in character. The tone is enthusiastic beyond what the evidence warrants. This should be read as a mechanistic hypothesis paper with one illustrative case — not as clinical evidence of efficacy. Larger randomised trials in Parkinson's disease are what is needed.", "abstract": "The Michael J. Fox Foundation has been funding research on Parkinson's disease for 35 years, but has yet to find a cure. This is due to a problem with the philosophy behind the development of modern medical treatments. In this paper, we will introduce \"smart medicine\" with a substance that can solve all the problems of central nervous system drugs. The substance is the smallest diatomic molecule, the hydrogen molecule. Due to their size, hydrogen molecules can easily penetrate the cell membrane and enter the brain. In the midbrain of Parkinson's disease patients, hydroxyl radicals generated by the Fenton reaction cause a chain reaction of oxidation of dopamine, but hydrogen entering the midbrain can convert the hydroxyl radicals into water molecules and inhibit the oxidation of dopamine. In this paper, we focus on the etiology of neurological diseases, especially Parkinson's disease, and present a case in which hydrogen inhalation improves the symptoms of Parkinson's disease, such as body bending and hand tremor. And we confidently state that if Michael J. Fox encountered \"smart medicine\" that could be realized with molecular hydrogen, he would not be a \"lucky man\" but a \"super-lucky man.\"", "conclusion": "And we confidently state that if Michael J. Fox encountered \"smart medicine\" that could be realized with molecular hydrogen, he would not be a \"lucky man\" but a \"super-lucky man.\"" }, { "pmid": "38945250", "year": 2024, "title": "d-aspartate, an amino-acid important for human health, supports anaerobic respiration in several Campylobacter species.", "title_en": null, "title_de": "d-Aspartat, eine für die menschliche Gesundheit wichtige Aminosäure, unterstützt die anaerobe Atmung bei mehreren Campylobacter-Arten.", "journal": "Research in microbiology", "authors": "Benoit et al.", "author_search": "benoit benoit", "doi": "10.1016/j.resmic.2024.104219", "doi_url": "https://doi.org/10.1016/j.resmic.2024.104219", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38945250/", "url": "https://h2medicine.org/studies/study-benoit-2024-aspartate-amino-acid-important/", "methods": [ "unspecified" ], "indications": [ "sports-exercise", "neurology" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2024 · Benoit — d-aspartate, an amino-acid important for human health, supports anaerobic respiration in several Campylobacter species.", "summary": "Certain gut bacteria in the Campylobacter family can use d-aspartate — a signalling molecule important to the human nervous system — as a nutrient source for anaerobic growth, using molecular hydrogen as an electron donor. This in-vitro microbiology study identified the gene responsible and raises questions about whether these bacteria compete with the host for neurologically important molecules. (Research in Microbiology, 2024.)", "assessment": "This is an in-vitro microbiology study — all experiments were performed in bacterial cultures. Molecular hydrogen in this paper is a bacterial metabolic substrate, not a therapeutic agent. The study does not investigate H₂ therapy, H₂-rich water, or any H₂ health intervention. Its inclusion in the H₂ database reflects the broad categorisation of H₂-related research. The findings about pathogen scavenging of d-aspartate are scientifically novel, but no human or animal data are presented. No health recommendations can be derived from this study.", "abstract": "Despite being classified as microaerophilic microorganisms, most Campylobacter species can grow anaerobically, using formate or molecular hydrogen (H2) as electron donors, and various nitrogenous and sulfurous compounds as electron acceptors. Herein, we showed that both l-asparagine (l-Asn) and l-aspartic acid (l-Asp) bolster H2-driven anaerobic growth in several Campylobacter species, whereas the d-enantiomer form of both asparagine (d-Asn) and aspartic acid (d-Asp) only increased anaerobic growth in Campylobacter concisus strain 13826 and Campylobacter ureolyticus strain NCTC10941. A gene annotated as racD encoding for a putative d/l-Asp racemase was identified in the genome of both strains. Disruption of racD in Cc13826 resulted in the inability of the mutant strain to use either d-enantiomer during anaerobic growth. Hence, our results suggest that the racD gene is required for campylobacters to use either d-Asp or d-Asn. The use of d-Asp by various human opportunistic bacterial pathogens, including C. concisus, C. ureolyticus, and also possibly select strains of Campylobacter gracilis, Campylobacter rectus and Campylobacter showae, is significant, because d-Asp is an important signal molecule for both human nervous and neuroendocrine systems. To our knowledge, this is the first report of pathogens scavenging a d-amino acid essential for human health.", "conclusion": "ureolyticus, and also possibly select strains of Campylobacter gracilis, Campylobacter rectus and Campylobacter showae, is significant, because d-Asp is an important signal molecule for both human nervous and neuroendocrine systems. To our knowledge, this is the first report of pathogens scavenging a d-amino acid essential for human health." }, { "pmid": "38934271", "year": 2024, "title": "Poly(ionic liquid)-Flocculated Chlorella Loading Bactericidal and Antioxidant Hydrogel as a Biological Hydrogen Therapy for Diabetic Wound Dressing.", "title_en": null, "title_de": "Poly(ionische Flüssigkeit)-geflocktes Chlorella mit bakteriziden und antioxidativen Hydrogel als biologische Wasserstofftherapie für diabetische Wundauflagen.", "journal": "ACS applied materials & interfaces", "authors": "Xu et al.", "author_search": "xu xu", "doi": "10.1021/acsami.4c07104", "doi_url": "https://doi.org/10.1021/acsami.4c07104", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38934271/", "url": "https://h2medicine.org/studies/study-xu-2024-poly-ionic-liquid-flocculated/", "methods": [ "unspecified" ], "indications": [ "diabetes", "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2024 · Xu — Poly(ionic liquid)-Flocculated Chlorella Loading Bactericidal and Antioxidant Hydrogel as a Biological Hydrogen Therapy for Diabetic Wound Dressing.", "summary": "A hydrogel wound dressing that uses living algae to continuously produce H₂ on-site was engineered and tested on infected diabetic wounds in cell and animal models. The patch combined H₂-mediated antioxidant effects with antibacterial properties, reducing infection and promoting healing in laboratory settings. (ACS Applied Materials & Interfaces, 2024.)", "assessment": "This is an in-vitro and preclinical animal study on a novel wound dressing concept. The H₂-producing algae hydrogel is scientifically creative, but all evidence comes from cell cultures and mouse models. Diabetic wound healing in mice differs substantially from the clinical reality in human patients with diabetes. No human safety or efficacy data exist. The approach is at an early proof-of-concept stage and would require extensive development before clinical application. No health claims for diabetic wound care in humans should be derived from this data.", "abstract": "Infection and oxidative stress seriously hinder the healing of diabetic wounds, resulting in various serious health and clinical problems. Herein, a sustainable biological hydrogen (H2)-producing hyaluronic acid-based hydrogel patch (HAP-Chl) was constructed by loading an imidazolium-based poly(ionic liquid) (PIL) flocculated live Chlorella as a diabetic wound dressing. The PIL can flocculate Chlorella through electrostatic interactions between PIL and Chlorella to form Chlorella agglomerates, endowing the Chlorella in the central agglomerates with the ability to continuously produce H2 for 24 h under mild conditions. Combining the membrane disruption-related bactericidal mechanism of PIL and the antioxidant properties of the produced H2, HAP-Chl was determined to be antibacterial and antioxidant. In addition to exhibiting biocompatible and nontoxic activities, subsequent Staphylococcus aureus-infected chronic wound studies revealed that HAP-Chl is capable of promoting the healing of chronic wounds by effectively killing bacteria, reducing extensive ROS, relieving inflammation, and promoting the deposition of mature collagen and angiogenesis. This study provides a new strategy for constructing an in situ sustainable H2-producing hydrogel, enabling the formation of novel antibacterial and antioxidant material platforms with potential for wound dressing applications.", "conclusion": "In addition to exhibiting biocompatible and nontoxic activities, subsequent Staphylococcus aureus-infected chronic wound studies revealed that HAP-Chl is capable of promoting the healing of chronic wounds by effectively killing bacteria, reducing extensive ROS, relieving inflammation, and promoting the deposition of mature collagen and angiogenesis. This study provides a new strategy for construct" }, { "pmid": "38895823", "year": 2024, "title": "Hydrogen-treated CoCrMo alloy: a novel approach to enhance biocompatibility and mitigate inflammation in orthopedic implants.", "title_en": null, "title_de": "Mit Wasserstoff behandelte CoCrMo-Legierung: Ein neuartiger Ansatz zur Verbesserung der Biokompatibilität und Abschwächung von Entzündungen bei orthopädischen Implantaten.", "journal": "Journal of materials chemistry. B", "authors": "Lin et al.", "author_search": "lin lin", "doi": "10.1039/d4tb00725e", "doi_url": "https://doi.org/10.1039/d4tb00725e", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38895823/", "url": "https://h2medicine.org/studies/study-lin-2024-treated-cocrmo-alloy-approach/", "methods": [ "unspecified" ], "indications": [ "joints-rheumatology", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2024 · Lin — Hydrogen-treated CoCrMo alloy: a novel approach to enhance biocompatibility and mitigate inflammation in orthopedic implants.", "summary": "Treating the surface of a metal alloy used in orthopedic implants with hydrogen reduced free radicals by 85% in cell models, improved cell compatibility, and promoted new bone formation in an initial animal test. The approach involves electrochemically charging the alloy surface with hydrogen to just a shallow depth. (Journal of Materials Chemistry B, 2024.)", "assessment": "This is an in-vitro and early preclinical animal study on a biomaterials surface modification. The hydrogen treatment of CoCrMo is a novel concept with plausible antioxidant mechanisms. However, results from cell cultures and a single animal test cannot be extrapolated to outcomes in human orthopedic implant surgery. The study does not describe what animal was used, how many, or over what period. Long-term stability of the hydrogen-rich surface layer in a biological environment is not established. This is exploratory materials science — considerable further development is needed before clinical relevance can be assessed.", "abstract": "In recent decades, orthopedic implants have been widely used as materials to replace human bone tissue functions. Among these, metal implants play a crucial role. Metals with better chemical stability, such as stainless steel, titanium alloys, and cobalt-chromium-molybdenum (CoCrMo) alloy, are commonly used for long-term applications. However, good chemical stability can result in poor tissue integration between the tissue and the implant, leading to potential inflammation risks. This study creates hydrogenated CoCrMo (H-CoCrMo) surfaces, which have shown promise as anti-inflammatory orthopedic implants. Using the electrochemical cathodic hydrogen-charging method, the surface of the CoCrMo alloy was hydrogenated, resulting in improved biocompatibility, reduced free radicals, and an anti-inflammatory response. Hydrogen diffusion to a depth of approximately 106 ± 27 nm on the surface facilitated these effects. This hydrogen-rich surface demonstrated a reduction of 85.2% in free radicals, enhanced hydrophilicity as evidenced by a decrease in a contact angle from 83.5 ± 1.9° to 52.4 ± 2.2°, and an increase of 11.4% in hydroxyapatite deposition surface coverage. The cell study results revealed a suppression of osteosarcoma cell activity to 50.8 ± 2.9%. Finally, the in vivo test suggested the promotion of new bone formation and a reduced inflammatory response. These findings suggest that electrochemical hydrogen charging can effectively modify CoCrMo surfaces, offering a potential solution for improving orthopedic implant outcomes through anti-inflammatory mechanisms.", "conclusion": "Finally, the in vivo test suggested the promotion of new bone formation and a reduced inflammatory response. These findings suggest that electrochemical hydrogen charging can effectively modify CoCrMo surfaces, offering a potential solution for improving orthopedic implant outcomes through anti-inflammatory mechanisms." }, { "pmid": "38863026", "year": 2024, "title": "Early Hydrogen-Oxygen Gas Mixture Inhalation in Patients with Aneurysmal Subarachnoid Hemorrhage (HOMA): study protocol for a randomized controlled trial.", "title_en": null, "title_de": "Frühe Inhalation eines Wasserstoff-Sauerstoff-Gasgemischs bei Patienten mit aneurysmatischer Subarachnoidalblutung (HOMA): Studienprotokoll für eine randomisierte kontrollierte Studie.", "journal": "Trials", "authors": "Lin et al.", "author_search": "lin lin", "doi": "10.1186/s13063-024-08231-5", "doi_url": "https://doi.org/10.1186/s13063-024-08231-5", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38863026/", "url": "https://h2medicine.org/studies/study-lin-2024-early-oxygen-mixture-inhalation/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "neurology", "skin-aging", "fundamentals-safety" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2024 · Lin — Early Hydrogen-Oxygen Gas Mixture Inhalation in Patients with Aneurysmal Subarachnoid Hemorrhage (HOMA): study protocol for a randomized controlled trial.", "summary": "This is the published protocol for the first large-scale randomised controlled trial of hydrogen therapy in aneurysmal subarachnoid haemorrhage (aSAH): 206 patients will inhale a 67% hydrogen / 33% oxygen gas mixture for 8 hours daily in the ICU, targeting delayed cerebral ischaemia and cerebral vasospasm. This is a protocol paper — results are not yet available. (Trials, 2024.)", "assessment": "A well-designed protocol with appropriate sample size (n=206), a hard primary endpoint, and a registered trial number. Important caveat: this is a protocol paper — no efficacy or safety results are available. The trial design is sound: open-label RCT, single centre, 7-day treatment window starting within 72h of aSAH, comparison against oxygen-only inhalation. Limitations of the design include open-label (not blinded), single-centre, and the Chinese population context. Results, when published, will be a landmark for H₂ research in neurocritical care.", "abstract": "BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening neurosurgical emergency with a high mortality rate. Delayed cerebral ischemia (DCI) and cerebral vasospasm (CVS) are delayed products of early brain injury (EBI), which may constitute the principal determinant of an unfavorable patient prognosis. Consequently, the mitigation of DCI and CVS assumes paramount significance in the pursuit of enhanced patient outcomes. However, except for oral nimodipine, there is no effective therapy available in the current guideline. Hence, the exigency arises to proffer novel treatment paradigms. The diversity of hydrogen therapeutic targets has been largely reported in basic research, unveiling its latent capacity to ameliorate EBI in aSAH patients. METHODS: Early Hydrogen-Oxygen Gas Mixture Inhalation in Patients with Aneurysmal Subarachnoid Hemorrhage (HOMA), a single-center, prospective, open-labeled, randomized controlled clinical trial, endeavors to evaluate the efficacy and safety of hydrogen-oxygen gas mixture inhalation therapy in aSAH patients. A cohort of 206 patients will be randomized to either hydrogen-oxygen gas mixture inhalation group (8 h per day, 3 L/min, hydrogen concentration of 67%, oxygen concentration of 33%) or oxygen inhalation group (8 h per day, 3 L/min, oxygen concentration of 33%) within 72 h after aSAH and treated for 7 days in the ICU ward. The primary outcomes are the incidence of DCI and CVS during hospitalization. DISCUSSION: The HOMA aims to evaluate the effectiveness of hydrogen-oxygen gas mixture inhalation therapy in preventing DCI or CVS and improving outcomes in aSAH patients. Notably, this is the first large-scale trial of hydrogen therapy in aSAH patients. Given that the Chinese population represents a significant portion of the global population and the increasing incidence of stroke due to aging, optimizing patient care is vital. Given the current challenges in aSAH patient outcomes, initiating more prospective clinical trials is essential. Recent research has shown hydrogen's therapeutic potential, aligning with EBI in aSAH, driving our exploration of hydrogen therapy's mechanisms in post-aneurysm rupture damage. ETHICS AND DISSEMINATION: The protocol for the HOMA study was approved by the Ethics Committee of Beijing Tiantan Hospital, Capital Medical University (KY 2022-020-02). All results of the present study will be published in peer-reviewed journals and presented at relevant conferences. TRIAL REGISTRATION: ClinicalTrials.gov NCT05282836. Registered on March 16, 2022.", "conclusion": "TRIAL REGISTRATION: ClinicalTrials.gov NCT05282836. Registered on March 16, 2022." }, { "pmid": "38855154", "year": 2024, "title": "Hydrogen-rich water alleviates constipation by attenuating oxidative stress through the sirtuin1/nuclear factor-erythroid-2-related factor 2/heme oxygenase-1 signaling pathway.", "title_en": null, "title_de": "Wasserstoffreiches Wasser lindert Verstopfung durch Abschwächung des oxidativen Stresses über den Sirtuin1/Nuclear-Factor-Erythroid-2-related-Factor-2/Häm-Oxygenase-1-Signalweg.", "journal": "World journal of gastroenterology", "authors": "Chen et al.", "author_search": "chen chen", "doi": "10.3748/wjg.v30.i20.2709", "doi_url": "https://doi.org/10.3748/wjg.v30.i20.2709", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38855154/", "url": "https://h2medicine.org/studies/study-chen-2024-alleviates-constipation-attenuating-oxidative/", "methods": [ "saline-iv", "drinking-hrw" ], "indications": [ "neurology", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2024 · Chen — Hydrogen-rich water alleviates constipation by attenuating oxidative stress through the sirtuin1/nuclear factor-erythroid-2-related factor 2/heme oxygenase-1 signaling pathway.", "summary": "In constipated rats, hydrogen-rich water (HRW) improved stool output, intestinal motility, and gut microbiota composition by reducing oxidative stress through a specific protective signalling pathway. The study also identified two metabolites (β-leucine and traumatic acid) that may mediate the benefit by activating a key antioxidant regulator. (World Journal of Gastroenterology, 2024.)", "assessment": "This is an animal study (rat model of constipation). The mechanistic evidence — including the SIRT1 inhibitor rescue experiment — is methodologically sound and the pathway is plausible. However, results from loperamide-induced constipation in rats cannot be directly applied to human constipation, which has diverse causes (diet, neurological, drug-related, etc.). The identified metabolites (β-leucine, traumatic acid) are interesting but their relevance in human gut physiology is unknown. No human data exist for this specific intervention. The study is a well-designed preclinical investigation that supports further research, not a clinical recommendation.", "abstract": "BACKGROUND: Constipation, a highly prevalent functional gastrointestinal disorder, induces a significant burden on the quality of patients' life and is associated with substantial healthcare expenditures. Therefore, identifying efficient therapeutic modalities for constipation is of paramount importance. Oxidative stress is a pivotal contributor to colonic dysmotility and is the underlying pathology responsible for constipation symptoms. Consequently, we postulate that hydrogen therapy, an emerging and promising intervention, can serve as a safe and efficacious treatment for constipation. AIM: To determine whether hydrogen-rich water (HRW) alleviates constipation and its potential mechanism. METHODS: Constipation models were established by orally loperamide to Sprague-Dawley rats. Rats freely consumed HRW, and were recorded their 24 h total stool weight, fecal water content, and charcoal propulsion rate. Fecal samples were subjected to 16S rDNA gene sequencing. Serum non-targeted metabolomic analysis, malondialdehyde, and superoxide dismutase levels were determined. Colonic tissues were stained with hematoxylin and eosin, Alcian blue-periodic acid-Schiff, reactive oxygen species (ROS) immunofluorescence, and immunohistochemistry for cell growth factor receptor kit (c-kit), PGP 9.5, sirtuin1 (SIRT1), nuclear factor-erythroid-2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Quantitative real-time PCR and western blot analysis were conducted to determine the expression level of SIRT1, Nrf2 and HO-1. A rescue experiment was conducted by intraperitoneally injecting the SIRT1 inhibitor, EX527, into constipated rats. NCM460 cells were induced with H2O2 and treated with the metabolites to evaluate ROS and SIRT1 expression. RESULTS: HRW alleviated constipation symptoms by improving the total amount of stool over 24 h, fecal water content, charcoal propulsion rate, thickness of the intestinal mucus layer, c-kit expression, and the number of intestinal neurons. HRW modulated intestinal microbiota imbalance and abnormalities in serum metabolism. HRW could also reduce intestinal oxidative stress through the SIRT1/Nrf2/HO-1 signaling pathway. This regulatory effect on oxidative stress was confirmed via an intraperitoneal injection of a SIRT1 inhibitor to constipated rats. The serum metabolites, β-leucine (β-Leu) and traumatic acid, were also found to attenuate H2O2-induced oxidative stress in NCM460 cells by up-regulating SIRT1. CONCLUSION: HRW attenuates constipation-associated intestinal oxidative stress via SIRT1/Nrf2/HO-1 signaling pathway, modulating gut microbiota and serum metabolites. β-Leu and traumatic acid are potential metabolites that upregulate SIRT1 expression and reduce oxidative stress.", "conclusion": "HRW attenuates constipation-associated intestinal oxidative stress via SIRT1/Nrf2/HO-1 signaling pathway, modulating gut microbiota and serum metabolites. β-Leu and traumatic acid are potential metabolites that upregulate SIRT1 expression and reduce oxidative stress." }, { "pmid": "38795705", "year": 2024, "title": "Gut bacteria convert glucocorticoids into progestins in the presence of hydrogen gas.", "title_en": null, "title_de": "Darmbakterien wandeln Glucocorticoide in Gegenwart von Wasserstoffgas in Gestagene um.", "journal": "Cell", "authors": "McCurry et al.", "author_search": "mccurry mc curry", "doi": "10.1016/j.cell.2024.05.005", "doi_url": "https://doi.org/10.1016/j.cell.2024.05.005", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38795705/", "url": "https://h2medicine.org/studies/study-mccurry-2024-gut-bacteria-convert-glucocorticoids/", "methods": [ "inhalation" ], "indications": [ "neurology", "pregnancy" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2024 · McCurry — Gut bacteria convert glucocorticoids into progestins in the presence of hydrogen gas.", "summary": "Two common gut bacteria can chemically transform stress hormones (glucocorticoids) into sex hormones and neurosteroids (progestins) — and this conversion is significantly boosted by hydrogen gas produced by other gut bacteria. The bacterial progestins include allopregnanolone (the active ingredient in an FDA-approved postpartum depression drug), and their levels are elevated in feces from pregnant humans. (Cell, 2024.)", "assessment": "This is an in-vitro mechanistic study (bacterial cultures, genomics, cell expression systems) with supporting observational human fecal data. It is a landmark paper in gut microbiome research, published in Cell, revealing a completely new dimension of how gut bacteria interact with host steroid metabolism. The H₂ involved is endogenous microbial H₂ — not an exogenous H₂ therapy. While the findings have profound implications for understanding the gut-brain axis and pregnancy physiology, no intervention or treatment is studied. The clinical implications (e.g., can modulating gut H₂ producers affect hormone levels or depression risk?) remain entirely speculative at this stage.", "abstract": "Recent studies suggest that human-associated bacteria interact with host-produced steroids, but the mechanisms and physiological impact of such interactions remain unclear. Here, we show that the human gut bacteria Gordonibacter pamelaeae and Eggerthella lenta convert abundant biliary corticoids into progestins through 21-dehydroxylation, thereby transforming a class of immuno- and metabo-regulatory steroids into a class of sex hormones and neurosteroids. Using comparative genomics, homologous expression, and heterologous expression, we identify a bacterial gene cluster that performs 21-dehydroxylation. We also uncover an unexpected role for hydrogen gas production by gut commensals in promoting 21-dehydroxylation, suggesting that hydrogen modulates secondary metabolism in the gut. Levels of certain bacterial progestins, including allopregnanolone, better known as brexanolone, an FDA-approved drug for postpartum depression, are substantially increased in feces from pregnant humans. Thus, bacterial conversion of corticoids into progestins may affect host physiology, particularly in the context of pregnancy and women's health.", "conclusion": "Levels of certain bacterial progestins, including allopregnanolone, better known as brexanolone, an FDA-approved drug for postpartum depression, are substantially increased in feces from pregnant humans. Thus, bacterial conversion of corticoids into progestins may affect host physiology, particularly in the context of pregnancy and women's health." }, { "pmid": "38757665", "year": 2024, "title": "Hydrogen Therapy Reverses Cancer-Associated Fibroblasts Phenotypes and Remodels Stromal Microenvironment to Stimulate Systematic Anti-Tumor Immunity.", "title_en": null, "title_de": "Die Wasserstofftherapie kehrt die Phänotypen krebsassoziierter Fibroblasten um und remodelliert die Stroma-Mikroumgebung, um eine systemische Antitumor-Immunität zu stimulieren.", "journal": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)", "authors": "Meng et al.", "author_search": "meng meng", "doi": "10.1002/advs.202401269", "doi_url": "https://doi.org/10.1002/advs.202401269", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38757665/", "url": "https://h2medicine.org/studies/study-meng-2024-reverses-cancer-associated-fibroblasts/", "methods": [ "unspecified" ], "indications": [ "cancer", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2024 · Meng — Hydrogen Therapy Reverses Cancer-Associated Fibroblasts Phenotypes and Remodels Stromal Microenvironment to Stimulate Systematic Anti-Tumor Immunity.", "summary": "In cell and animal cancer models, a magnesium-based H₂-releasing implant reversed the immune-suppressive behaviour of cancer-associated fibroblasts, turning „cold“ tumors that resist the immune system into „hot“ ones that attract cancer-fighting T cells. The approach simultaneously killed tumor cells directly and activated systemic anti-tumor immunity. (Advanced Science, 2024.)", "assessment": "This is an in-vitro and preclinical animal study. The mechanistic strategy — using H₂ to reprogram immune-suppressive fibroblasts in the tumor microenvironment — is novel and scientifically compelling. However, all results come from cell cultures and mouse tumor models, which frequently fail to translate to human cancer outcomes. CAF biology in human tumors is considerably more complex than in mouse models. No human safety or efficacy data exist. This is exploratory preclinical cancer research, not clinical evidence.", "abstract": "Tumor microenvironment (TME) plays an important role in the tumor progression. Among TME components, cancer-associated fibroblasts (CAFs) show multiple tumor-promoting effects and can induce tumor immune evasion and drug-resistance. Regulating CAFs can be a potential strategy to augment systemic anti-tumor immunity. Here, the study observes that hydrogen treatment can alleviate intracellular reactive oxygen species of CAFs and reshape CAFs' tumor-promoting and immune-suppressive phenotypes. Accordingly, a controllable and TME-responsive hydrogen therapy based on a CaCO3 nanoparticles-coated magnesium system (Mg-CaCO3) is developed. The hydrogen therapy by Mg-CaCO3 can not only directly kill tumor cells, but also inhibit pro-tumor and immune suppressive factors in CAFs, and thus augment immune activities of CD4+ T cells. As implanted in situ, Mg-CaCO3 can significantly suppress tumor growth, turn the \"cold\" primary tumor into \"hot\", and stimulate systematic anti-tumor immunity, which is confirmed by the bilateral tumor transplantation models of \"cold tumor\" (4T1 cells) and \"hot tumor\" (MC38 cells). This hydrogen therapy system reverses immune suppressive phenotypes of CAFs, thus providing a systematic anti-tumor immune stimulating strategy by remodeling tumor stromal microenvironment.", "conclusion": "As implanted in situ, Mg-CaCO3 can significantly suppress tumor growth, turn the \"cold\" primary tumor into \"hot\", and stimulate systematic anti-tumor immunity, which is confirmed by the bilateral tumor transplantation models of \"cold tumor\" (4T1 cells) and \"hot tumor\" (MC38 cells). This hydrogen therapy system reverses immune suppressive phenotypes of CAFs, thus providing a systematic anti-tumor i" }, { "pmid": "38688598", "year": 2024, "title": "Molecular Hydrogen as a Promising Therapy Could Be Linked With Increased Resting Treg Cells or Decreased Fas+ T Cell Subsets in a IgG4-PF-ILD Patient: A Case Report.", "title_en": null, "title_de": "Molekularer Wasserstoff als vielversprechende Therapie könnte mit erhöhten ruhenden Treg-Zellen oder verminderten Fas+-T-Zell-Subpopulationen bei einem IgG4-PF-ILD-Patienten zusammenhängen: Ein Fallbericht.", "journal": "In vivo (Athens, Greece)", "authors": "Lui et al.", "author_search": "lui lui", "doi": "10.21873/invivo.13600", "doi_url": "https://doi.org/10.21873/invivo.13600", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38688598/", "url": "https://h2medicine.org/studies/study-lui-2024-promising-could-linked-increased/", "methods": [ "unspecified" ], "indications": [ "respiratory", "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2024 · Lui — Molecular Hydrogen as a Promising Therapy Could Be Linked With Increased Resting Treg Cells or Decreased Fas+ T Cell Subsets in a IgG4-PF-ILD Patient: A Case Report.", "summary": "An 85-year-old woman with progressive fibrosing interstitial lung disease complicated by hospital-acquired pneumonia showed noticeable improvement in lung infiltrations on chest X-ray by day four of hydrogen-assisted therapy, alongside measurable immune changes: resting Treg cells rose, while Fas+ T cell subsets declined. (In Vivo, 2024.)", "assessment": "A case report with unusually specific immune phenotyping that adds biological depth beyond simple clinical observation. The Treg/Fas+ pattern is consistent with H₂'s proposed anti-inflammatory immunomodulation. Limitations: n=1; 85-year-old with multiple concurrent interventions; the 4-day radiological improvement timeline may reflect antibiotic response to pneumonia rather than H₂; no baseline immune data from before H₂ initiation was described relative to pre-disease; no standardised lung function endpoints. Hypothesis-generating only.", "abstract": "BACKGROUND/AIM: Progressive fibrosing interstitial lung disease (PF-ILD) refers to a group of chronic lung conditions commonly associated with immunoglobulin G4-related disorders. It is characterized by progressive scarring (fibrosis) within the pulmonary interstitium, resulting in respiratory failure and early mortality. Some patients do not respond to standard therapeutic interventions. Numerous studies have confirmed the anti-inflammatory and antioxidant properties of molecular hydrogen in various disease models. CASE REPORT: In this report, we present a case study of an 85-year-old female diagnosed with suspected IgG4-related PF-ILD complicated by hospital-acquired pneumonia. On the fourth day of hydrogen-assisted therapy, a noticeable improvement in lung infiltrations was observed in chest X-rays as the patient gradually progressed towards weaning off mechanical ventilation. To assess treatment responses, we compared immune phenotypes before and after hydrogen treatment. A marked increase was observed in resting regulatory T cell levels after treatment, accompanied by a notable decrease in Fas+ helper T cell and cytotoxic T cell subtypes. CONCLUSION: This case study highlights the effectiveness of hydrogen-assisted therapy in managing PF-ILD complicated by pneumonia, warranting further research in the future.", "conclusion": "This case study highlights the effectiveness of hydrogen-assisted therapy in managing PF-ILD complicated by pneumonia, warranting further research in the future." }, { "pmid": "38679666", "year": 2024, "title": "Combined use of hydrogen-rich water and enzyme-digested edible bird's nest improves PMA/LPS-impaired wound healing in human inflammatory gingival tissue equivalents.", "title_en": null, "title_de": "Die kombinierte Anwendung von wasserstoffreichem Wasser und enzymatisch verdautem essbarem Vogelnest verbessert die durch PMA/LPS beeinträchtigte Wundheilung in humanen entzündlichen Zahnfleischgewebe-Äquivalenten.", "journal": "Human cell", "authors": "Wang et al.", "author_search": "wang wang", "doi": "10.1007/s13577-024-01065-y", "doi_url": "https://doi.org/10.1007/s13577-024-01065-y", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38679666/", "url": "https://h2medicine.org/studies/study-wang-2024-combined-use-enzyme-digested/", "methods": [ "drinking-hrw" ], "indications": [ "skin-aging", "immune-system", "oral-health", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2024 · Wang — Combined use of hydrogen-rich water and enzyme-digested edible bird's nest improves PMA/LPS-impaired wound healing in human inflammatory gingival tissue equivalents.", "summary": "In a laboratory model of inflamed human gum tissue, the combination of hydrogen-rich water and a processed form of edible bird's nest significantly counteracted the wound-healing damage caused by an inflammatory stimulus. When used together, these two substances outperformed either one alone in reducing inflammation and restoring tissue integrity. (Human Cell, 2024.)", "assessment": "This is an in-vitro study using a 3D human gingival tissue model — no human patients are involved. The tissue equivalent is more sophisticated than a simple cell line, but still does not replicate the full physiology of human gum tissue. The combination of hydrogen-rich water and bird's nest extract is unusual and requires confirmation in clinical trials before any conclusions about oral wound healing in humans can be drawn. Results from this inflammation model cannot be directly applied to periodontal disease or oral wound healing in patients.", "abstract": "Gingival wound healing plays a critical role in maintaining oral health. However, this process can be delayed by oxidative stress and excessive inflammatory responses. In this study, we established a human inflammatory gingival tissue equivalent (iGTE) to investigate the inhibitory effects of hydrogen-rich water (HW), enzyme-digested edible bird's nest (EBND) and sialic acid (SA) on PMA (an inducer of oxidative free radicals)- and LPS (an inflammatory stimulus)-impaired wound healing. The iGTE was constructed by human gingival fibroblasts (hGFs), keratinocytes and macrophages under three-dimensional conditions. Wounds in the iGTE and hGF/keratinocyte monolayers were created by mechanical injury. Tissues and cells were pretreated with HW, EBND, and SA, and then exposed to the inflammatory and oxidative environment induced by PMA (10 ng/mL) and LPS (250 ng/mL). The inflammatory cytokines IL-6 and IL-8 were quantitatively analyzed by ELISA. Histopathological image analysis was performed by HE and immunofluorescence staining. In the iGTE, PMA/LPS significantly reduced the epithelial thickness while causing a decrease in K8/18, E-cadherin, laminin and elastin expression and an increase in COX-2 expression along with ulcer-like lesions. In mechanically scratched hGFs and keratinocyte monolayers, PMA/LPS significantly impaired wound healing, and promoted the secretion of IL-6 and IL-8. Pretreatment of HW, EBND, and SA significantly suppressed PMA/LPS-induced wound healing delay and inflammatory responses in cell monolayers, as well as in the iGTE. Remarkably, the combined use of HW and EBND exhibited particularly robust results. Combined use of HW and EBND may be applied for the prevention and treatment of wound healing delay.", "conclusion": "Remarkably, the combined use of HW and EBND exhibited particularly robust results. Combined use of HW and EBND may be applied for the prevention and treatment of wound healing delay." }, { "pmid": "38666450", "year": 2024, "title": "Endogenous Melanin and Hydrogen-Based Specific Activated Theranostics Nanoagents: A Novel Multi-Treatment Paradigm for Rheumatoid Arthritis.", "title_en": null, "title_de": "Endogenes Melanin und wasserstoffbasierte spezifisch aktivierte theranostische Nanoagenzien: Ein neuartiges Multi-Behandlungsparadigma für rheumatoide Arthritis", "journal": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)", "authors": "Chen et al.", "author_search": "chen chen", "doi": "10.1002/advs.202401046", "doi_url": "https://doi.org/10.1002/advs.202401046", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38666450/", "url": "https://h2medicine.org/studies/study-chen-2024-endogenous-melanin-specific-activated/", "methods": [ "inhalation" ], "indications": [ "skin-aging", "joints-rheumatology", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2024 · Chen et al. — Endogenous Melanin and Hydrogen-Based Specific Activated Theranostics Nanoagents: A Novel Multi-Treatment Paradigm for Rheumatoid Arthritis", "summary": "Researchers developed nanoparticles (MAHI NGs) that release molecular hydrogen, melanin nanoparticles, and a clinical fluorescent dye directly into inflamed joints — guided by the specific chemical environment of rheumatoid arthritis (RA). In cell-culture and animal experiments, the combination of hydrogen's antioxidant/anti-inflammatory effect and photothermal melanin ablation of inflamed fibroblasts achieved strong synergistic suppression of RA-related inflammation. This is a purely preclinical in-vitro/in-vivo study; no human data exist yet.", "assessment": "An innovative preclinical concept combining nanotechnology, photothermal therapy, and molecular hydrogen — demonstrated in cell culture and mouse models. The synergistic H₂ + melanin approach is mechanistically compelling. Honest limitation: this is an in-vitro/animal study with no human data. Nanoagent translation to clinical RA therapy is complex and long-term. No therapeutic claims for humans can be derived from this work at this stage.", "abstract": "Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by excessive proliferation of rheumatoid arthritis synovial fibroblasts (RASFs) and accumulation of inflammatory cytokines. Exploring the suppression of RASFs and modulation of the RA microenvironment is considered a comprehensive strategy for RA. In this work, specifically activated nanoagents (MAHI NGs) based on the hypoxic and weakly acidic RA microenvironment are developed to achieve a second near-infrared fluorescence (NIR-II FL)/photoacoustic (PA) dual-model imaging-guided multi-treatment. Due to optimal size, the MAHI NGs passively accumulate in the diseased joint region and undergo rapid responsive degradation, precisely releasing functionalized components: endogenous melanin-nanoparticles (MNPs), hydrogen gas (H2), and indocyanine green (ICG). The released MNPs play a crucial role in ablating RASFs within the RA microenvironment through photothermal therapy (PTT) guided by accurate PA imaging. However, the regional hyperthermia generated by PTT may exacerbate reactive oxygen species (ROS) production and inflammatory response following cell lysis. Remarkably, under the acidic microenvironment, the controlled release of H2 exhibits precise synergistic antioxidant and anti-inflammatory effects with MNPs. Moreover, the ICG, the second near-infrared dye currently approved for clinical use, possesses excellent NIR-II FL imaging properties that facilitate the diagnosis of deep tissue diseases and provide the right time-point for PTT.", "conclusion": "Remarkably, under the acidic microenvironment, the controlled release of H2 exhibits precise synergistic antioxidant and anti-inflammatory effects with MNPs. Moreover, the ICG, the second near-infrared dye currently approved for clinical use, possesses excellent NIR-II FL imaging properties that facilitate the diagnosis of deep tissue diseases and provide the right time-point for PTT." }, { "pmid": "38642971", "year": 2024, "title": "The synergistic potential of hydrogen inhalation and hyperbaric oxygen therapy.", "title_en": null, "title_de": "Das synergistische Potenzial von Wasserstoffinhalation und hyperbarer Sauerstofftherapie", "journal": "Journal of vascular surgery", "authors": "James et al.", "author_search": "james james", "doi": "10.1016/j.jvs.2023.11.067", "doi_url": "https://doi.org/10.1016/j.jvs.2023.11.067", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38642971/", "url": "https://h2medicine.org/studies/study-james-2024-synergistic-inhalation-hyperbaric-oxygen/", "methods": [ "inhalation" ], "indications": [ "other" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2024 · James et al. — The Synergistic Potential of Hydrogen Inhalation and Hyperbaric Oxygen Therapy", "summary": "This review article in the Journal of Vascular Surgery examines whether combining hydrogen inhalation with hyperbaric oxygen therapy (HBOT) could produce synergistic therapeutic benefits. The authors discuss the distinct and potentially complementary mechanisms of both gas therapies. As no abstract text is available in this record, the full scope of the analysis cannot be summarised here — please consult the original article via the DOI.", "assessment": "This is a review article (no new experimental data). Its specific conclusions cannot be fully evaluated here because the abstract is not available in this record. The topic — combining H₂ inhalation with HBOT — is scientifically relevant and mechanistically plausible, but the quality of the synthesis, breadth of evidence, and any clinical conclusions require direct review of the original text. No therapeutic claims can be derived from this summary.", "abstract": null, "conclusion": null }, { "pmid": "38637698", "year": 2024, "title": "Hydrogen inhalation therapy for inflammation and eye diseases: a review of the literature.", "title_en": null, "title_de": "Wasserstoffinhalationstherapie bei Entzündungen und Augenerkrankungen: Eine Übersichtsarbeit der Literatur", "journal": "Eye (London, England)", "authors": "Takefuji", "author_search": "takefuji takefuji", "doi": "10.1038/s41433-024-03083-4", "doi_url": "https://doi.org/10.1038/s41433-024-03083-4", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38637698/", "url": "https://h2medicine.org/studies/study-takefuji-2024-inhalation-inflammation-eye-diseases/", "methods": [ "inhalation" ], "indications": [ "eye", "immune-system" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2024 · Takefuji — Hydrogen Inhalation Therapy for Inflammation and Eye Diseases: A Review of the Literature", "summary": "This literature review in the journal Eye surveys published evidence on hydrogen inhalation therapy for inflammatory conditions — with a focus on eye diseases. The author examines how H₂'s antioxidant and anti-inflammatory properties may be relevant to ocular pathology. As the abstract is not available in this record, a detailed content summary cannot be provided — please consult the original article via the DOI for full findings.", "assessment": "This is a review article — a literature synthesis, not a new clinical study. The topic of H₂ therapy for eye diseases is scientifically plausible given H₂'s anti-inflammatory profile, but human evidence in ophthalmology specifically is limited. The abstract is not available in this database record, so the specific conclusions, quality of included evidence, and clinical relevance cannot be evaluated here. Accessing the original publication (DOI: 10.1038/s41433-024-03083-4) is necessary for a full assessment.", "abstract": null, "conclusion": null }, { "pmid": "38479178", "year": 2024, "title": "Decoupling the mutual promotion of inflammation and oxidative stress mitigates cognitive decline and depression-like behavior in rmTBI mice by promoting myelin renewal and neuronal survival.", "title_en": null, "title_de": "Die Entkopplung der gegenseitigen Förderung von Entzündung und oxidativem Stress mildert den kognitiven Abbau und depressionsähnliches Verhalten bei rmTBI-Mäusen durch Förderung der Myelinerneuerung und des Neuronenüberlebens", "journal": "Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie", "authors": "Lu et al.", "author_search": "lu lu", "doi": "10.1016/j.biopha.2024.116419", "doi_url": "https://doi.org/10.1016/j.biopha.2024.116419", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38479178/", "url": "https://h2medicine.org/studies/study-lu-2024-decoupling-mutual-promotion-inflammation/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise", "neurology", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2024 · Lu et al. — Decoupling the Mutual Promotion of Inflammation and Oxidative Stress Mitigates Cognitive Decline and Depression-Like Behavior in rmTBI Mice by Promoting Myelin Renewal and Neuronal Survival", "summary": "In mice subjected to repetitive mild traumatic brain injury (rmTBI), early treatment with hydrogen-rich water (HRW) significantly reduced oxidative stress and inflammasome activation, preserved myelin integrity, and improved both cognitive performance and depression-like behaviour. The study maps the exact time windows of molecular pathology after rmTBI and shows that HRW interrupts the self-reinforcing cycle of inflammation and oxidative damage. This is an animal study; results cannot yet be directly extrapolated to humans.", "assessment": "A well-designed animal study using multiple complementary methods (immunoblotting, MR spectroscopy, immunofluorescence, behavioural testing) to investigate HRW in repetitive mild TBI. The mechanistic story — HRW decouples the mutual reinforcement of inflammation and oxidative stress — is internally consistent and supported by converging data. Honest limitation: this is an animal study (mice) with no human data. Mouse TBI models are imperfect proxies for human concussion syndromes. H₂ dosing via drinking water is inherently imprecise. Translating these findings to humans requires dedicated clinical studies.", "abstract": "BACKGROUND: Repetitive mild traumatic brain injury (rmTBI) can lead to somatic, emotional, and cognitive symptoms that persist for years after the initial injury. Although the ability of various treatments to promote recovery after rmTBI has been explored, the optimal time window for early intervention after rmTBI is unclear. Previous research has shown that hydrogen-rich water (HRW) can diffuse through the blood-brain - barrier, attenuate local oxidative stress, and reduce neuronal apoptosis in patients with severe traumatic brain injury. However, research on the effect of HRW on rmTBI is scarce. AIMS: The objectives of this study were to explore the following changes after rmTBI and HRW treatment: (i) temporal changes in inflammasome activation and oxidative stress-related protein expression through immunoblotting, (ii) temporal changes in neuron/myelin-related metabolite concentrations in vivo through magnetic resonance spectroscopy, (iii) myelin structural changes in late-stage rmTBI via immunofluorescence, and (iv) postinjury anxiety/depression-like behaviors and spatial learning and memory impairment. RESULTS: NLRP-3 expression in the rmTBI group was elevated at 7 and 14 DPI, and inflammasome marker levels returned to normal at 30 DPI. Oxidative stress persisted throughout the first month postinjury. HRW replacement significantly decreased Nrf2 expression in the prefrontal cortex and hippocampal CA2 region at 14 and 30 DPI, respectively. Edema and local gliosis in the hippocampus and restricted diffusion in the thalamus were observed on MR-ADC images. The tCho/tCr ratio in the rmTBI group was elevated, and the tNAA/tCr ratio was decreased at 30 DPI. Compared with the mice in the other groups, the mice in the rmTBI group spent more time exploring the open arms in the elevated plus maze (P < 0.05) and were more active in the maze (longer total distance traveled). In the sucrose preference test, the rmTBI group exhibited anhedonia. In the Morris water maze test, the latency to find the hidden platform in the rmTBI group was longer than that in the sham and HRW groups (P < 0.05). CONCLUSION: Early intervention with HRW can attenuate inflammasome assembly and reduce oxidative stress after rmTBI. These changes may restore local oligodendrocyte function, promote myelin repair, prevent axonal damage and neuronal apoptosis, and alleviate depression-like behavior and cognitive impairment.", "conclusion": "Early intervention with HRW can attenuate inflammasome assembly and reduce oxidative stress after rmTBI. These changes may restore local oligodendrocyte function, promote myelin repair, prevent axonal damage and neuronal apoptosis, and alleviate depression-like behavior and cognitive impairment." }, { "pmid": "38399533", "year": 2024, "title": "The Benefit of Hydrogen Gas as an Adjunctive Therapy for Chronic Obstructive Pulmonary Disease.", "title_en": null, "title_de": "Der Nutzen von Wasserstoffgas als adjuvante Therapie bei chronisch obstruktiver Lungenerkrankung.", "journal": "Medicina (Kaunas, Lithuania)", "authors": "Liu et al.", "author_search": "liu liu", "doi": "10.3390/medicina60020245", "doi_url": "https://doi.org/10.3390/medicina60020245", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38399533/", "url": "https://h2medicine.org/studies/study-liu-2024-benefit-adjunctive-chronic-obstructive/", "methods": [ "inhalation" ], "indications": [ "neurology", "respiratory", "immune-system", "oxidative-stress", "fundamentals-safety" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2024 · Liu — The Benefit of Hydrogen Gas as an Adjunctive Therapy for Chronic Obstructive Pulmonary Disease.", "summary": "Six COPD patients who added hydrogen gas inhalation (30 min, three times daily for 30 days) to standard treatment showed significant improvements in symptom burden scores (CAT) and dyspnoea scale (mMRC) — but no changes in lung function, sleep quality, inflammation markers, or oxidative stress markers. No adverse effects occurred. (Medicina, 2024.)", "assessment": "Honest pilot data with important null findings alongside positive symptom scores. The disconnect between subjective symptom improvement and objective function/biomarker measures is clinically important and should not be glossed over. Limitations: n=6 is far too small for reliable statistical inference; no control or placebo group; open-label; unknown if improvements persist beyond 30 days; the platelet count change requires explanation. The study's value is in providing preliminary data and identifying endpoints for a properly powered trial. Cannot support clinical recommendations in isolation.", "abstract": "Background and Objectives: Recent studies suggest that hydrogen gas possesses anti-inflammatory, antioxidant, and anti-apoptotic properties. This study aimed to explore the therapeutic potential of hydrogen gas and assess its safety and tolerability in individuals with chronic obstructive pulmonary disease (COPD). Materials and Methods: Enrolled COPD patients received standard treatments along with additional hydrogen inhalation for 30 min in the morning, afternoon, and evening over a 30-day period. The assessment included changes in the COPD Assessment Test (CAT), the modified Medical Research Council (mMRC) Dyspnea Scale, lung function, sleep quality, inflammation markers, and oxidative stress markers before and after hydrogen inhalation. Results: Six patients participated in this study. Patients 2, 3, 4, 5, and 6 demonstrated improvements in CAT scores following hydrogen gas intervention, with patients 2, 4, 5, and 6 also showing improvements in mMRC scores. Statistically, this study revealed significant improvements in CAT [15.5 (10.5-19.75) vs. 8.5 (3-13.5); p = 0.043] and mMRC scores [2.5 (1-4) vs. 2 (0-3.25); p = 0.046] before and after intervention, respectively. However, no significant differences were observed in lung function, DLCO, sleep quality, and 6 MWT before and after hydrogen therapy. CBC examination showed a significant difference in platelet count before and after treatment [247 (209.75-298.75) vs. 260 (232.75-314.5); p = 0.043], respectively, while other blood tests, inflammation markers, and oxidative stress markers did not exhibit significant differences before and after hydrogen therapy. All patients experienced no obvious side-effects. Conclusions: Adjuvant therapy with hydrogen gas demonstrated symptom improvements in specific COPD patients, and no significant adverse effects were observed in any of the patients. Hydrogen gas may also exert a modulatory effect on platelet count.", "conclusion": "Adjuvant therapy with hydrogen gas demonstrated symptom improvements in specific COPD patients, and no significant adverse effects were observed in any of the patients. Hydrogen gas may also exert a modulatory effect on platelet count." }, { "pmid": "38395800", "year": 2024, "title": "Molecular hydrogen attenuates sepsis-induced cardiomyopathy in mice by promoting autophagy.", "title_en": null, "title_de": "Molekularer Wasserstoff schwächt die sepsisinduzierte Kardiomyopathie bei Mäusen durch Förderung der Autophagie ab", "journal": "BMC anesthesiology", "authors": "Cui et al.", "author_search": "cui cui", "doi": "10.1186/s12871-024-02462-4", "doi_url": "https://doi.org/10.1186/s12871-024-02462-4", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38395800/", "url": "https://h2medicine.org/studies/study-cui-2024-attenuates-sepsis-induced-cardiomyopathy/", "methods": [ "inhalation", "saline-iv" ], "indications": [ "cardiovascular", "immune-system" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2024 · Cui et al. — Molecular Hydrogen Attenuates Sepsis-Induced Cardiomyopathy in Mice by Promoting Autophagy", "summary": "In a mouse model of sepsis-induced cardiomyopathy (SIC), molecular hydrogen inhalation significantly improved 7-day survival, reduced cardiac tissue inflammation, and lowered troponin I levels — effects that operated through promotion of autophagy and mitophagy. When autophagy was pharmacologically blocked, the protective effect of H₂ was reversed, confirming autophagy as a key mechanistic link. This is an animal study; human data are not yet available.", "assessment": "A mechanistically rigorous animal study that identifies autophagy/mitophagy promotion as the likely mechanism by which H₂ protects the heart in sepsis. The reversal experiment with bafilomycin A1 adds meaningful causal weight. Honest limitation: this is an animal study (mice, CLP model) with no human data. CLP models do not fully replicate the heterogeneity of human sepsis. Clinical translation would require safety and efficacy studies in humans. The work is an important step toward understanding H₂'s cardiac protective mechanism, not a clinical recommendation.", "abstract": "BACKGROUND: Approximately 40 to 60% of patients with sepsis develop sepsis-induced cardiomyopathy (SIC), which is associated with a substantial increase in mortality. We have found that molecular hydrogen (H2) inhalation improved the survival rate and cardiac injury in septic mice. However, the mechanism remains unclear. This study aimed to explore the regulatory mechanism by which hydrogen modulates autophagy and its role in hydrogen protection of SIC. METHODS: Cecal ligation and puncture (CLP) was used to induce sepsis in adult C57BL/6J male mice. The mice were randomly divided into 4 groups: Sham, Sham + 2% hydrogen inhalation (H2), CLP, and CLP + H2 group. The 7-day survival rate was recorded. Myocardial pathological scores were calculated. Myocardial troponin I (cTnI) levels in serum were detected, and the levels of autophagy- and mitophagy-related proteins in myocardial tissue were measured. Another four groups of mice were also studied: CLP, CLP + Bafilomycin A1 (BafA1), CLP + H2, and CLP + H2 + BafA1 group. Mice in the BafA1 group received an intraperitoneal injection of the autophagy inhibitor BafA1 1 mg/kg 1 h after operation. The detection indicators remained the same as before. RESULTS: The survival rate of septic mice treated with H2 was significantly improved, myocardial tissue inflammation was improved, serum cTnI level was decreased, autophagy flux was increased, and mitophagy protein content was decreased (P < 0.05). Compared to the CLP + H2 group, the CLP + H2 + BafA1 group showed a decrease in autophagy level and 7-day survival rate, an increase in myocardial tissue injury and cTnI level, which reversed the protective effect of hydrogen (P < 0.05). CONCLUSION: Hydrogen exerts protective effect against SIC, which may be achieved through the promotion of autophagy and mitophagy.", "conclusion": "Hydrogen exerts protective effect against SIC, which may be achieved through the promotion of autophagy and mitophagy." }, { "pmid": "38382672", "year": 2024, "title": "Charge neutralization and β-elimination cleavage mechanism of family 42 L-rhamnose-α-1,4-D-glucuronate lyase revealed using neutron crystallography.", "title_en": null, "title_de": "Ladungsneutralisierung und β-Eliminierungs-Spaltungsmechanismus der L-Rhamnose-α-1,4-D-Glucuronat-Lyase der Familie 42, aufgeklärt mittels Neutronenkristallographie", "journal": "The Journal of biological chemistry", "authors": "Yano et al.", "author_search": "yano yano", "doi": "10.1016/j.jbc.2024.105774", "doi_url": "https://doi.org/10.1016/j.jbc.2024.105774", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38382672/", "url": "https://h2medicine.org/studies/study-yano-2024-charge-neutralization-elimination-cleavage/", "methods": [ "unspecified" ], "indications": [ "joints-rheumatology" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2024 · Yano et al. — Charge Neutralization and β-Elimination Cleavage Mechanism of Family 42 L-Rhamnose-α-1,4-D-Glucuronate Lyase Revealed Using Neutron Crystallography", "summary": "This structural biochemistry study uses neutron and X-ray crystallography to determine, at atomic resolution, exactly how a fungal enzyme cleaves gum arabic — a complex carbohydrate used as an emulsion stabilizer. Neutron crystallography reveals the positions of individual hydrogen atoms in the enzyme's active site, clarifying the catalytic mechanism. This paper is not about molecular hydrogen therapy — the term „hydrogen“ here refers to structural hydrogen atoms in a protein crystal, not to H₂ gas.", "assessment": "Important clarification: this paper has no relevance to molecular hydrogen (H₂) therapy. It is a structural biochemistry study using neutron crystallography to map hydrogen atoms in a fungal enzyme active site — a completely different use of the word „hydrogen.“ It is included in this database due to keyword overlap, but provides no evidence regarding H₂ gas as an antioxidant, anti-inflammatory, or therapeutic agent. There are no clinical implications for hydrogen medicine from this work.", "abstract": "Gum arabic (GA) is widely used as an emulsion stabilizer and edible coating and consists of a complex carbohydrate moiety with a rhamnosyl-glucuronate group capping the non-reducing ends. Enzymes that can specifically cleave the glycosidic chains of GA and modify their properties are valuable for structural analysis and industrial application. Cryogenic X-ray crystal structure of GA-specific L-rhamnose-α-1,4-D-glucuronate lyase from Fusarium oxysporum (FoRham1), belonging to the polysaccharide lyase (PL) family 42, has been previously reported. To determine the specific reaction mechanism based on its hydrogen-containing enzyme structure, we performed joint X-ray/neutron crystallography of FoRham1. Large crystals were grown in the presence of L-rhamnose (a reaction product), and neutron and X-ray diffraction datasets were collected at room temperature at 1.80 and 1.25 Å resolutions, respectively. The active site contained L-rhamnose and acetate, the latter being a partial analog of glucuronate. Incomplete H/D exchange between Arg166 and acetate suggested that a strong salt-bridge interaction was maintained. Doubly deuterated His105 and deuterated Tyr150 supported the interaction between Arg166 and the acetate. The unique hydrogen-rich environment functions as a charge neutralizer for glucuronate and stabilizes the oxyanion intermediate. The NE2 atom of His85 was deprotonated and formed a hydrogen bond with the deuterated O1 hydroxy of L-rhamnose, indicating the function of His85 as the base/acid catalyst for bond cleavage via β-elimination. Asp83 functions as a pivot between the two catalytic histidine residues by bridging them. This His-His-Asp structural motif is conserved in the PL 24, 25, and 42 families.", "conclusion": "Asp83 functions as a pivot between the two catalytic histidine residues by bridging them. This His-His-Asp structural motif is conserved in the PL 24, 25, and 42 families." }, { "pmid": "38284276", "year": 2024, "title": "Successful treatment of Behçet's disease ulcers and skin lesions with hydrogen water.", "title_en": null, "title_de": "Erfolgreiche Behandlung von Ulzera und Hautläsionen beim Morbus Behçet mit Wasserstoffwasser.", "journal": "International journal of dermatology", "authors": "Guan et al.", "author_search": "guan guan", "doi": "10.1111/ijd.16958", "doi_url": "https://doi.org/10.1111/ijd.16958", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38284276/", "url": "https://h2medicine.org/studies/study-guan-2024-successful-behcet-disease-ulcers/", "methods": [ "drinking-hrw" ], "indications": [ "skin-aging" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2024 · Guan — Successful treatment of Behçet's disease ulcers and skin lesions with hydrogen water.", "summary": "A case report describing the successful use of hydrogen water in treating oral ulcers and skin lesions associated with Behçet's disease — a rare systemic vasculitis for which conventional therapies often provide incomplete relief. Full abstract text was not available for this entry; the finding is based on title and metadata only. (International Journal of Dermatology, 2024.)", "assessment": "No abstract was available for this entry — assessment is based on title and journal metadata only. As a case report in a dermatology journal, this represents a hypothesis-generating anecdote. Behçet's disease is an appropriate target indication for H₂'s proposed anti-inflammatory mechanism, and hydrogen water is a low-risk intervention. However, no efficacy conclusions can be drawn without the full text. Limitations: n=1 (assumed); no control; details of administration, dose, and duration unknown.", "abstract": null, "conclusion": null }, { "pmid": "37929512", "year": 2024, "title": "Successful treatment of myalgic encephalomyelitis/chronic fatigue syndrome using hydrogen gas: four case reports.", "title_en": null, "title_de": "Erfolgreiche Behandlung der myalgischen Enzephalomyelitis/des chronischen Erschöpfungssyndroms mit Wasserstoffgas: Vier Fallberichte.", "journal": "Medical gas research", "authors": "Hirano et al.", "author_search": "hirano hirano", "doi": "10.4103/2045-9912.385441", "doi_url": "https://doi.org/10.4103/2045-9912.385441", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/37929512/", "url": "https://h2medicine.org/studies/study-hirano-2024-successful-myalgic-encephalomyelitis-chronic/", "methods": [ "inhalation" ], "indications": [ "sports-exercise" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2024 · Hirano — Successful treatment of myalgic encephalomyelitis/chronic fatigue syndrome using hydrogen gas: four case reports.", "summary": "Four patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) — one of medicine's most intractable and poorly understood conditions — are reported to have improved with hydrogen gas inhalation therapy. Full abstract text was not available for this entry; findings are based on title and metadata only. (Medical Gas Research, 2024.)", "assessment": "No abstract was available for this entry — assessment is based on title and metadata only. ME/CFS is a clinically important indication with no approved treatments, making this series worth noting. H₂'s proposed mechanism (mitochondrial support, neuroinflammation reduction, ROS scavenging) aligns with current ME/CFS pathophysiology hypotheses. However, four case reports without controls cannot establish efficacy. Limitations: n=4; no control arm; full details unavailable; ME/CFS diagnosis criteria and outcome measures unknown; placebo response in ME/CFS can be substantial.", "abstract": null, "conclusion": null }, { "pmid": "39258790", "year": 2024, "title": "High-concentration hydrogen inhalation mitigates sepsis-associated encephalopathy in mice by improving mitochondrial dynamics", "title_en": null, "title_de": "Das Einatmen von hochkonzentriertem Wasserstoff mildert die sepsisassoziierte Enzephalopathie bei Mäusen durch Verbesserung der Mitochondrien-Dynamik", "journal": "CNS Neuroscience & Therapeutics", "authors": "Cui et al.", "author_search": "cui cui", "doi": "10.1111/cns.70021", "doi_url": "https://doi.org/10.1111/cns.70021", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39258790/", "url": "https://h2medicine.org/studies/study-cui-2024-high-concentration-sepsis-encephalopathy-mitochondrial/", "methods": [ "inhalation" ], "indications": [ "neurology", "fundamentals", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2024 · Cui — High-concentration hydrogen inhalation mitigates sepsis-associated encephalopathy in mice by improving mitochondrial dynamics", "summary": "Inhaling high-concentration hydrogen (67%) improved the 7-day survival rate and recognition memory in septic mice — through protection of the mitochondria (the power plants of nerve cells) and less inflammation. (Preclinical study, CNS Neuroscience & Therapeutics, 2024.)", "assessment": "The study deepens the mechanism of why H₂ acts neuroprotectively — it shows concretely the mitochondrial level and thus complements the classic antioxidant picture from Ohsawa 2007. For everyday applications it is only indirectly relevant: it concerns an intensive-care emergency inhalation with 67% H₂, not hydrogen water for everyday use — a transfer to consumer products is not permissible. Its value lies as a mechanistic building block. Limitations, stated honestly: purely preclinical (mouse), a very high and clinically unusual H₂ concentration, and the authors themselves phrase the mechanism cautiously with „might“.", "abstract": "Sepsis-associated encephalopathy (SAE) is a neuronal injury with poor prognosis. Mitochondrial dysfunction is critical in SAE development, and hydrogen gas (H2) has a protective effect on septic mice. This study aimed to investigate the effect of high concentration (67%) of H2 on SAE and whether it is related to mitochondrial biogenesis and mitochondrial dynamics. A mouse sepsis model was induced by cecal ligation and puncture. The mice inhalated 67% H2 for 1 h at 1 and 6 h post-surgery, respectively. The 7-day survival rate was recorded. Cognitive function was assessed using the Y-maze test and Morris water maze test. Serum inflammatory factors, antioxidant enzymes, as well as mitochondrial function indexes including mitochondrial membrane potential (MMP) and ATP in the hippocampal tissue were evaluated 24 h after surgery. Mitochondrial dynamic proteins (DRP1 and MFN2) and biosynthetic proteins (PGC-1α, NRF2, and TFAM) in the hippocampal tissue were detected. Moreover, the morphology of mitochondria was observed by transmission electron microscopy. Inhalation of 67% H2 improved the 7-day survival rates and recognition memory function of septic mice, alleviated brain antioxidant enzyme activity (SOD and CAT), and reduced serum proinflammatory cytokine levels. H2 inhalation also enhanced the expression of MFN2 and mitochondrial biogenesis-related factors (PGC-1α, NRF2, and TFAM) and decreased the expression of fission protein (DRP1), leading to improvement in mitochondrial function, as evidenced by MMP and ATP levels. Inhalation of high concentration (67%) of H2 in septic mice improved the survival rate and reduced neuronal injury. Its mechanism might be mediated by enhancing mitochondrial biogenesis and mitochondrial dynamics.", "conclusion": "Inhalation of high concentration (67%) of H2 in septic mice improved the survival rate and reduced neuronal injury. Its mechanism might be mediated by enhancing mitochondrial biogenesis and mitochondrial dynamics." }, { "pmid": "39328786", "year": 2024, "title": "Natural hydrogen gas and engineered microalgae prevent acute lung injury in sepsis", "title_en": null, "title_de": "Natürliches Wasserstoffgas und maßgeschneiderte Mikroalgen verhindern akuten Lungenschaden bei Sepsis", "journal": "Materials Today Bio", "authors": "Wang et al.", "author_search": "wang wang", "doi": "10.1016/j.mtbio.2024.101247", "doi_url": "https://doi.org/10.1016/j.mtbio.2024.101247", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/39328786/", "url": "https://h2medicine.org/studies/study-wang-2024-engineered-microalgae-acute-lung-injury-sepsis/", "methods": [ "inhalation" ], "indications": [ "respiratory", "oxidative-stress", "fundamentals" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2024 · Wang — Natural hydrogen gas and engineered microalgae prevent acute lung injury in sepsis", "summary": "Inhaled hydrogen gas protects the lung in sepsis — and a novel nanosystem of H₂-releasing particles plus microalgae (DQB@C) amplifies this protection in a mouse model by curbing inflammation, oxidative stress and „ferroptosis“ (iron-dependent cell death). (Materials Today Bio, 2024 — preclinical mechanistic study.)", "assessment": "Interesting as evidence that H₂ research in 2024 goes far beyond „drinking water“ — here molecular hydrogen is characterised down to the level of individual phosphorylated proteins (Esam, ZO-1) and linked to highly topical cell-death mechanisms (ferroptosis). This supports the general plausibility of anti-inflammatory and anti-oxidative H₂ effects. Limitations, honestly and clearly: this is a preclinical study in mice and cells — no human evidence at all. Moreover, the actual main finding is a technical drug-carrier system (DQB@C nanoparticles with ammonia borane as a chemical H₂ source) that shares only the active agent with classic applications (H₂ water, inhalation), not the mode of use. It works as a „look into the research pipeline“, not as a promise of efficacy. Note: the DOI in the source dataset was erroneous (pointed to a different journal) — therefore omitted; the canonical reference is the PubMed link.", "abstract": "Hydrogen gas and microalgae both exist in the natural environment. We aimed to integrate hydrogen gas and biology nano microalgae together to expand the treatment options in sepsis. Phosphoproteomics, metabolomics and proteomics data were obtained from mice undergoing cecum ligation and puncture (CLP) and inhalation of hydrogen gas. All omics analysis procedure were accordance with standards. Multi R packages were used in single cell and spatial transcriptomics analysis to identify primary cells expressing targeted genes, and the genes' co-expression relationships in sepsis related lung landscape. Then, network pharmacology method was used to identify candidate drugs. We used hydrophobic-force-driving self-assembly method to construct dihydroquercetin (DQ) nanoparticle. To cooperate with molecular hydrogen, ammonia borane (B) was added to DQ surface. Then, Chlorella vulgaris (C) was used as biological carrier to improve self-assembly nanoparticle. Vivo and vitro experiments were both conducted to evaluate anti-inflammation, anti-ferroptosis, anti-infection and organ protection capability. As a result, we identified Esam and Zo-1 were target phosphorylation proteins for molecular hydrogen treatment in lung. Ferroptosis and glutathione metabolism were two target pathways. Chlorella vulgaris improved the dispersion of DQB and reconstructed morphological features of DQB, formed DQB@C nano-system (size = 307.3 nm, zeta potential = -22mv), with well infection-responsive hydrogen release capability and biosafety. In addition, DQB@C was able to decrease oxidative stress and inflammation factors accumulation in lung cells. Through increasing expression level of Slc7a11/xCT and decreasing Cox2 level to participate with the regulation of ferroptosis. Also, DQB@C played lung and multi organ protection and anti-inflammation roles on CLP mice. Our research proposed DQB@C as a novel biology nano-system with enormous potential on treatment for sepsis related acute lung injury to solve the limitation of hydrogen gas utilization in clinics.", "conclusion": "Also, DQB@C played lung and multi organ protection and anti-inflammation roles on CLP mice. Our research proposed DQB@C as a novel biology nano-system with enormous potential on treatment for sepsis related acute lung injury to solve the limitation of hydrogen gas utilization in clinics." }, { "pmid": "36708550", "year": 2023, "title": "A Systematic Review of Molecular Hydrogen Therapy in Cancer Management.", "title_en": null, "title_de": "Ein systematischer Review der molekularen Wasserstofftherapie in der Krebsbehandlung", "journal": "Asian Pacific Journal of Cancer Prevention", "authors": "Mohd Noor et al.", "author_search": "mohd noor mohd noor", "doi": "10.31557/apjcp.2023.24.1.37", "doi_url": "https://doi.org/10.31557/apjcp.2023.24.1.37", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36708550/", "url": "https://h2medicine.org/studies/study-mohd-noor-2023-cancer-management-systematic-review/", "methods": [ "unspecified" ], "indications": [ "cancer", "oxidative-stress", "immune-system" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2023 · Mohd Noor — A Systematic Review of Molecular Hydrogen Therapy in Cancer Management", "summary": "A systematic review of 27 studies classifies molecular hydrogen as a promising adjunctive cancer therapy. Across different cancer types and H₂ delivery routes, the authors found consistent improvements in survival, quality of life, blood values and tumour reduction. (Asian Pacific J. Cancer Prevention, 2023.)", "assessment": "A useful overview document that bundles the breadth of H₂ cancer research in one place — well suited to convey plausibility and the state of research without relying on a single small study. It serves as serious evidence that H₂ is being seriously investigated as an adjunctive (adjuvant) option. Limitation, stated honestly: as a review it generates no primary evidence of its own; its strength depends on the quality of the 27 included studies, which are heterogeneous and partly small/uncontrolled, with a risk of publication bias. Important in communication: H₂ is discussed here as a complement to standard therapy, not as a cure or replacement — curative claims would be inadmissible.", "abstract": "BACKGROUND: Cancer remains a challenging target to cure, with present therapeutic methods unable to exhibit restorative outcomes without causing severe negative effects. Molecular hydrogen (H2) has been reported to be a promising adjunctive therapy for cancer treatment, having the capability to induce anti-proliferative, anti-oxidative, pro-apoptotic and anti-tumoural effects. This review summarises the findings from various articles on the mechanism, treatment outcomes, and overall effectiveness of H2 therapy on cancer management. METHODS: Using Cochrane, PubMed, and Google Scholar as the search engines, full-text articles in the scope of the study, written in English and within 10 years of publication were selected. RESULTS: Out of the 677 articles, 27 articles fulfilled the eligibility criteria, where data was compiled into a table, outlining the general characteristics and findings. Throughout the different forms of H2 administration, study design and types of cancers reported, outcomes were found to be consistent. CONCLUSION: From our analysis, H2 plays a promising therapeutic role as an independent therapy as well as an adjuvant in combination therapy, resulting in an overall improvement in survivability, quality of life, blood parameters, and tumour reduction. Although more comprehensive research is needed, given the promising outcomes, H2 is worth considering for use as a complement to current cancer therapy.", "conclusion": "From our analysis, H2 plays a promising therapeutic role as an independent therapy as well as an adjuvant in combination therapy, resulting in an overall improvement in survivability, quality of life, blood parameters, and tumour reduction. Although more comprehensive research is needed, given the promising outcomes, H2 is worth considering for use as a complement to current cancer therapy." }, { "pmid": "36978884", "year": 2023, "title": "Molecular Hydrogen: From Molecular Effects to Stem Cells Management and Tissue Regeneration", "title_en": null, "title_de": "Molekularer Wasserstoff: Von molekularen Effekten bis zum Stammzell-Management und zur Geweberegeneration", "journal": "Antioxidants (Basel)", "authors": "Artamonov et al.", "author_search": "artamonov artamonov", "doi": "10.3390/antiox12030636", "doi_url": "https://doi.org/10.3390/antiox12030636", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36978884/", "url": "https://h2medicine.org/studies/study-artamonov-2023-stem-cells-tissue-regeneration/", "methods": [ "unspecified" ], "indications": [ "fundamentals", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2023 · Artamonov — Molecular Hydrogen: From Molecular Effects to Stem Cells Management and Tissue Regeneration", "summary": "H₂ as a tool of regenerative medicine: by the end of 2022, more than 2,000 papers on hydrogen medicine had appeared. This review systematises the molecular, cellular and systemic effects of H₂ — including its effect on stem cells — and sees in it a potentially effective approach to tissue regeneration. (Antioxidants, 2023.)", "assessment": "A broad orientation review from the journal Antioxidants (MDPI), useful as a map of the entire H₂ field and especially of the less well-known stem-cell/regeneration perspective. Mainly usable as evidence of the breadth and volume of research (2,000+ papers), not as a specific product argument. Limitation, stated honestly: a narrative review, no measurements of its own; the wording „potentially effective“ is deliberately cautious. In addition: the DOI listed in the raw data was erroneous (different publisher/year) and was omitted — please verify via the PubMed link.", "abstract": "It is known that molecular hydrogen is a relatively stable, ubiquitous gas that is a minor component of the atmosphere. At the same time, in recent decades molecular hydrogen has been shown to have diverse biological effects. By the end of 2022, more than 2000 articles have been published in the field of hydrogen medicine, many of which are original studies. Despite the existence of several review articles on the biology of molecular hydrogen, many aspects of the research direction remain unsystematic. Therefore, the purpose of this review was to systematize ideas about the nature, characteristics, and mechanisms of the influence of molecular hydrogen on various types of cells, including stem cells. The historical aspects of the discovery of the biological activity of molecular hydrogen are presented. The ways of administering molecular hydrogen into the body are described. The molecular, cellular, tissue, and systemic effects of hydrogen are also reviewed. Specifically, the effect of hydrogen on various types of cells, including stem cells, is addressed. The existing literature indicates that the molecular and cellular effects of hydrogen qualify it to be a potentially effective agent in regenerative medicine.", "conclusion": "Specifically, the effect of hydrogen on various types of cells, including stem cells, is addressed. The existing literature indicates that the molecular and cellular effects of hydrogen qualify it to be a potentially effective agent in regenerative medicine." }, { "pmid": "37988743", "year": 2023, "title": "Molecular Hydrogen: Emerging Treatment for Stroke Management", "title_en": null, "title_de": "Molekularer Wasserstoff: Aufkommende Behandlung für das Schlaganfall-Management", "journal": "Chemical Research in Toxicology", "authors": "Kuo et al.", "author_search": "kuo kuo", "doi": "10.1021/acs.chemrestox.3c00259", "doi_url": "https://doi.org/10.1021/acs.chemrestox.3c00259", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/37988743/", "url": "https://h2medicine.org/studies/study-kuo-2023-stroke-management/", "methods": [ "inhalation", "saline-iv", "drinking-hrw" ], "indications": [ "neurology", "cardiovascular", "fundamentals", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2023 · Kuo — Molecular Hydrogen: Emerging Treatment for Stroke Management", "summary": "Molecular hydrogen (H₂) is an emerging therapeutic approach in ischemic stroke — antioxidative, anti-inflammatory and anti-apoptotic. Across numerous preclinical and clinical studies (inhalation, infusion, H₂ water), favourable results were seen. (Review, Chemical Research in Toxicology, 2023.)", "assessment": "The work is a good overview that places H₂ across several routes of administration in stroke — including hydrogen water. But beware: stroke is an acute emergency, for which mainly inhalation and infusions are discussed here — no evidence that everyday H₂ water prevents or treats a stroke. Limitations, stated honestly: a pure review, no study of its own, a small number of authors, and the language remains throughout in the conditional („may“, „in the future“). Valuable as mechanistic and overarching context, not as proof of efficacy.", "abstract": "Ischemic stroke is a major cause of death and disability worldwide. However, only intravenous thrombolysis using mechanical thrombectomy or tissue plasminogen activator is considered an effective and approved treatment. Molecular hydrogen is an emerging therapeutic agent and has recently become a research focus. Molecular hydrogen is involved in antioxidative, anti-inflammatory, and antiapoptotic functions in normal physical processes and may play an important role in stroke management; it has been evaluated in numerous preclinical and clinical studies in several administration formats, including inhalation of hydrogen gas, intravenous or intraperitoneal injection of hydrogen-enriched solution, or drinking of hydrogen-enriched water. In addition to investigation of the underlying mechanisms, the safety and efficacy of using molecular hydrogen have been carefully evaluated, and favorable outcomes have been achieved. All available evidence indicates that molecular hydrogen may be a promising treatment option for stroke management in the future. This review aimed to provide an overview of the role of molecular hydrogen in the management of stroke and possible further modifications of treatment conditions and procedures in terms of dose, duration, and administration route.", "conclusion": "All available evidence indicates that molecular hydrogen may be a promising treatment option for stroke management in the future. This review aimed to provide an overview of the role of molecular hydrogen in the management of stroke and possible further modifications of treatment conditions and procedures in terms of dose, duration, and administration route." }, { "pmid": "38067515", "year": 2023, "title": "Molecular Hydrogen Therapy-A Review on Clinical Studies and Outcomes.", "title_en": null, "title_de": "Molekulare Wasserstofftherapie – Eine Übersichtsarbeit zu klinischen Studien und Ergebnissen", "journal": "Molecules (Basel, Switzerland)", "authors": "Johnsen et al.", "author_search": "johnsen johnsen", "doi": "10.3390/molecules28237785", "doi_url": "https://doi.org/10.3390/molecules28237785", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38067515/", "url": "https://h2medicine.org/studies/study-johnsen-2023-review-outcomes/", "methods": [ "inhalation" ], "indications": [ "cardiovascular", "cancer", "respiratory", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2023 · Johnsen et al. — Molecular Hydrogen Therapy — A Review on Clinical Studies and Outcomes", "summary": "This comprehensive review in Molecules analysed 81 identified clinical trials and 64 scientific publications on human studies of molecular hydrogen (H₂) therapy across a broad range of disease areas. Positive signals were found in cardiovascular disease, cancer, respiratory disease, central nervous system disorders, and infections, among others. The review also addresses practical challenges of H₂ administration — including its explosive hazard and low solubility — and asks: could hydrogen gas become a recognised drug substance in future clinical practice?", "assessment": "A valuable landscape review covering 81 clinical trials and 64 human publications on H₂ therapy — one of the most comprehensive such surveys available. Its strength is breadth; its limitation is that it is a narrative review, not a systematic meta-analysis. Effect sizes are not pooled, study quality is not formally graded. The honest verdict from the authors themselves: H₂ therapy shows promising signals across many disease areas, but whether it will achieve drug status remains an open question requiring larger, controlled trials. This is a review, not new experimental evidence.", "abstract": "With its antioxidant properties, hydrogen gas (H2) has been evaluated in vitro, in animal studies and in human studies for a broad range of therapeutic indications. A simple search of \"hydrogen gas\" in various medical databases resulted in more than 2000 publications related to hydrogen gas as a potential new drug substance. A parallel search in clinical trial registers also generated many hits, reflecting the diversity in ongoing clinical trials involving hydrogen therapy. This review aims to assess and discuss the current findings about hydrogen therapy in the 81 identified clinical trials and 64 scientific publications on human studies. Positive indications have been found in major disease areas including cardiovascular diseases, cancer, respiratory diseases, central nervous system disorders, infections and many more. The available administration methods, which can pose challenges due to hydrogens' explosive hazards and low solubility, as well as possible future innovative technologies to mitigate these challenges, have been reviewed. Finally, an elaboration to discuss the findings is included with the aim of addressing the following questions: will hydrogen gas be a new drug substance in future clinical practice? If so, what might be the administration form and the clinical indications?", "conclusion": "Finally, an elaboration to discuss the findings is included with the aim of addressing the following questions: will hydrogen gas be a new drug substance in future clinical practice? If so, what might be the administration form and the clinical indications?" }, { "pmid": "37913734", "year": 2023, "title": "The role of hydrogen therapy in Alzheimer's disease management: Insights into mechanisms, administration routes, and future challenges.", "title_en": null, "title_de": "Die Rolle der Wasserstofftherapie im Management der Alzheimer-Krankheit: Einblicke in Mechanismen, Verabreichungswege und zukünftige Herausforderungen", "journal": "Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie", "authors": "He et al.", "author_search": "he he", "doi": "10.1016/j.biopha.2023.115807", "doi_url": "https://doi.org/10.1016/j.biopha.2023.115807", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/37913734/", "url": "https://h2medicine.org/studies/study-he-2023-alzheimer-disease-management-insights/", "methods": [ "unspecified" ], "indications": [ "neurology", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2023 · He et al. — The Role of Hydrogen Therapy in Alzheimer's Disease Management: Insights into Mechanisms, Administration Routes, and Future Challenges", "summary": "This review comprehensively examines the therapeutic potential of molecular hydrogen in Alzheimer's disease (AD), focusing on how H₂ may counteract key pathological processes including oxidative stress, amyloid-beta metabolism, tau phosphorylation, neuroinflammation, and mitochondrial dysfunction. The authors survey mechanisms of action and routes of administration, and discuss the current challenges and future prospects for clinical application. No new experimental data are generated — this is a literature synthesis.", "assessment": "A well-structured review situating H₂ therapy within the complex molecular landscape of Alzheimer's disease. The mechanistic coverage is broad and scientifically grounded. Honest limitation: this is a review article, not an experimental study. Human clinical evidence for H₂ in AD specifically remains sparse. The review is best read as a research agenda and mechanistic framework — not as clinical guidance. The gap between mechanistic plausibility and proven efficacy in AD patients has not yet been bridged.", "abstract": "Alzheimer's disease (AD) is a progressive neurodegenerative disorder predominantly affecting the elderly. While conventional pharmacological therapies remain the primary treatment for AD, their efficacy is limited effectiveness and often associated with significant side effects. This underscores the urgent need to explore alternative, non-pharmacological interventions. Oxidative stress has been identified as a central player in AD pathology, influencing various aspects including amyloid-beta metabolism, tau phosphorylation, autophagy, neuroinflammation, mitochondrial dysfunction, and synaptic dysfunction. Among the emerging non-drug approaches, hydrogen therapy has garnered attention for its potential in mitigating these pathological conditions. This review provides a comprehensively overview of the therapeutic potential of hydrogen in AD. We delve into its mechanisms of action, administration routes, and discuss the current challenges and future prospects, with the aim of providing valuable insights to facilitate the clinical application of hydrogen-based therapies in AD management.", "conclusion": "This review provides a comprehensively overview of the therapeutic potential of hydrogen in AD. We delve into its mechanisms of action, administration routes, and discuss the current challenges and future prospects, with the aim of providing valuable insights to facilitate the clinical application of hydrogen-based therapies in AD management." }, { "pmid": "37269385", "year": 2023, "title": "Hydrogen therapy as a potential therapeutic intervention in heart disease: from the past evidence to future application.", "title_en": null, "title_de": "Die Wasserstofftherapie als potenzielle therapeutische Intervention bei Herzerkrankungen: Von der bisherigen Evidenz zur zukünftigen Anwendung", "journal": "Cellular and molecular life sciences : CMLS", "authors": "Saengsin et al.", "author_search": "saengsin saengsin", "doi": "10.1007/s00018-023-04818-4", "doi_url": "https://doi.org/10.1007/s00018-023-04818-4", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/37269385/", "url": "https://h2medicine.org/studies/study-saengsin-2023-therapeutic-intervention-heart-disease/", "methods": [ "inhalation", "saline-iv", "bath-topical", "drinking-hrw" ], "indications": [ "cardiovascular", "cancer", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2023 · Saengsin et al. — Hydrogen Therapy as a Potential Therapeutic Intervention in Heart Disease: From the Past Evidence to Future Application", "summary": "This comprehensive review in Cellular and Molecular Life Sciences synthesises in-vitro, animal, and clinical evidence for molecular hydrogen's protective effects in cardiovascular disease, covering its antioxidant, anti-inflammatory, and anti-apoptotic mechanisms. The authors specifically address ischemia-reperfusion injury, radiation-induced cardiac injury, atherosclerosis, chemotherapy-induced cardiotoxicity, and cardiac hypertrophy. Multiple delivery routes (inhalation, hydrogen-rich water drinking, intravenous hydrogen-rich saline, and organ bathing) are discussed. This is a review, not a new experiment.", "assessment": "A thorough and well-referenced review covering the breadth of H₂ cardiovascular research across in-vitro, animal, and clinical settings. The mechanistic discussion is nuanced and the delivery-route overview is practically useful. Honest limitation: this is a review article, not new experimental evidence. Clinical evidence for most of the specific cardiovascular applications discussed is still early-stage and requires larger controlled trials. The authors themselves note that intracellular mechanisms remain incompletely understood. No therapeutic conclusions for individual patients can be drawn from this review alone.", "abstract": "Cardiovascular disease is the leading cause of mortality worldwide. Excessive oxidative stress and inflammation play an important role in the development and progression of cardiovascular disease. Molecular hydrogen, a small colorless and odorless molecule, is considered harmless in daily life when its concentration is below 4% at room temperature. Owing to the small size of the hydrogen molecule, it can easily penetrate the cell membrane and can be metabolized without residue. Molecular hydrogen can be administered through inhalation, the drinking of hydrogen-rich water, injection with hydrogen-rich-saline, and bathing of an organ in a preservative solution. The utilization of molecular hydrogen has shown many benefits and can be effective for a wide range of purposes, from prevention to the treatment of diseases. It has been demonstrated that molecular hydrogen exerts antioxidant, anti-inflammatory, and antiapoptotic effects, leading to cardioprotective benefits. Nevertheless, the exact intracellular mechanisms of its action are still unclear. In this review, evidence of the potential benefits of hydrogen molecules obtained from in vitro, in vivo, and clinical investigations are comprehensively summarized and discussed with a focus on the cardiovascular aspects. The potential mechanisms involved in the protective effects of molecular hydrogen are also presented. These findings suggest that molecular hydrogen could be used as a novel treatment in various cardiovascular pathologies, including ischemic-reperfusion injury, cardiac injury from radiation, atherosclerosis, chemotherapy-induced cardiotoxicity, and cardiac hypertrophy.", "conclusion": "The potential mechanisms involved in the protective effects of molecular hydrogen are also presented. These findings suggest that molecular hydrogen could be used as a novel treatment in various cardiovascular pathologies, including ischemic-reperfusion injury, cardiac injury from radiation, atherosclerosis, chemotherapy-induced cardiotoxicity, and cardiac hypertrophy." }, { "pmid": "36930488", "year": 2023, "title": "Novel therapeutic approaches based on the pathological role of gut dysbiosis on the link between nonalcoholic fatty liver disease and insulin resistance.", "title_en": null, "title_de": "Neuartige therapeutische Ansätze auf Basis der pathologischen Rolle der Darmdysbiose für den Zusammenhang zwischen nichtalkoholischer Fettlebererkrankung und Insulinresistenz", "journal": "European review for medical and pharmacological sciences", "authors": "Bellucci et al.", "author_search": "bellucci bellucci", "doi": "10.26355/eurrev_202303_31558", "doi_url": "https://doi.org/10.26355/eurrev_202303_31558", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36930488/", "url": "https://h2medicine.org/studies/study-bellucci-2023-therapeutic-approaches-pathological-gut/", "methods": [ "unspecified" ], "indications": [ "diabetes", "metabolic", "liver", "immune-system" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2023 · Bellucci et al. — Novel Therapeutic Approaches Based on the Pathological Role of Gut Dysbiosis on the Link Between Non-Alcoholic Fatty Liver Disease and Insulin Resistance", "summary": "This review examines the interplay between gut dysbiosis, insulin resistance, and non-alcoholic fatty liver disease (NAFLD) — the most common chronic liver disease in the Western world — and surveys a broad range of therapeutic strategies including probiotics, prebiotics, fecal microbiota transplant, Chinese herbal medicine, dietary approaches, and minor therapies such as hydrogen-rich water. Hydrogen-rich water is mentioned as one of several experimental approaches showing potential to improve NAFLD's phenotypic pattern. This is a literature review, not a clinical study of H₂ therapy.", "assessment": "This paper is primarily a review of NAFLD and gut dysbiosis, in which hydrogen-rich water appears as one item in a long list of candidate interventions. It is not a H₂-focused review, and its coverage of the hydrogen evidence is minimal. As a review article, it produces no new experimental data. For those specifically interested in H₂ and NAFLD, this paper provides limited dedicated insight — it situates H₂ as a „minor therapy“ worth exploring, no more. More targeted H₂ NAFLD research would be needed to draw meaningful conclusions.", "abstract": "The growing global epidemic of obesity and type 2 diabetes mellitus has determined an increased prevalence of NAFLD (non-alcoholic fatty liver disease), making it the most common chronic liver disease in the Western world and a leading cause of liver transplantation. In the last few years, a rising number of studies conducted both on animal and human models have shown the existence of a close association between insulin resistance (IR), dysbiosis, and steatosis. However, all the mechanisms that lead to impaired permeability, inflammation, and fibrosis have not been fully clarified. Recently, new possible treatment modalities have received much attention. To reach the review purpose, a broad-ranging literature search on multidisciplinary research databases was performed using the following terms alone or in combination: \"NAFLD\", \"gut dysbiosis\", \"insulin resistance\", \"inflammation\", \"probiotics\", \"Chinese herbs\". The use of probiotics, prebiotics, symbiotics, postbiotics, fecal microbiota transplant (FMT), Chinese herbal medicine, antibiotics, diet (polyphenols and fasting diets), and minor therapies such as carbon nanoparticles, the MCJ protein, water rich in molecular hydrogen, seems to be able to improve the phenotypic pattern in NAFLD patients. In this review, we provide an overview of how IR and dysbiosis contribute to the development and progression of NAFLD, as well as the therapeutic strategies currently in use.", "conclusion": "The use of probiotics, prebiotics, symbiotics, postbiotics, fecal microbiota transplant (FMT), Chinese herbal medicine, antibiotics, diet (polyphenols and fasting diets), and minor therapies such as carbon nanoparticles, the MCJ protein, water rich in molecular hydrogen, seems to be able to improve the phenotypic pattern in NAFLD patients. In this review, we provide an overview of how IR and dysbi" }, { "pmid": "36571374", "year": 2023, "title": "The overlooked benefits of hydrogen-producing bacteria.", "title_en": null, "title_de": "Die übersehenen Vorteile wasserstoffproduzierender Bakterien", "journal": "Medical gas research", "authors": "Ichikawa et al.", "author_search": "ichikawa ichikawa", "doi": "10.4103/2045-9912.344977", "doi_url": "https://doi.org/10.4103/2045-9912.344977", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36571374/", "url": "https://h2medicine.org/studies/study-ichikawa-2023-overlooked-benefits-producing-bacteria/", "methods": [ "unspecified" ], "indications": [ "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2023 · Ichikawa et al. — The Overlooked Benefits of Hydrogen-Producing Bacteria", "summary": "This review in Medical Gas Research proposes a new explanatory framework for why certain intestinal bacteria are truly „beneficial“: they produce molecular hydrogen (H₂) in the gut, which then scavenges harmful hydroxyl radicals generated in mitochondria and protects cells from oxidative stress. The authors argue that the amount of H₂ produced by gut bacteria correlates with susceptibility to various diseases — offering a fresh microbiome-centred perspective on endogenous H₂ biology.", "assessment": "An intellectually stimulating perspective review proposing a new reason why certain gut bacteria are beneficial: their H₂ production provides systemic antioxidant protection. The framework is biologically coherent and mechanistically grounded. Honest limitation: this is a narrative review/perspective paper, not an experimental study. The correlation between gut H₂ production and disease has not been rigorously established through controlled human trials. This paper is best read as a thought-provoking hypothesis, not as established clinical fact.", "abstract": "Intestinal bacteria can be classified into \"beneficial bacteria\" and \"harmful bacteria.\" However, it is difficult to explain the mechanisms that make \"beneficial bacteria\" truly beneficial to human health. This issue can be addressed by focusing on hydrogen-producing bacteria in the intestines. Although it is widely known that molecular hydrogen can react with hydroxyl radicals, generated in the mitochondria, to protect cells from oxidative stress, the beneficial effects of hydrogen are not fully pervasive because it is not generally thought to be metabolized in vivo. In recent years, it has become clear that there is a close relationship between the amount of hydrogen produced by intestinal bacteria and various diseases, and this report discusses this relationship.", "conclusion": "Although it is widely known that molecular hydrogen can react with hydroxyl radicals, generated in the mitochondria, to protect cells from oxidative stress, the beneficial effects of hydrogen are not fully pervasive because it is not generally thought to be metabolized in vivo. In recent years, it has become clear that there is a close relationship between the amount of hydrogen produced by intest" }, { "pmid": "36567361", "year": 2023, "title": "Molecular Hydrogen: an Emerging Therapeutic Medical Gas for Brain Disorders.", "title_en": null, "title_de": "Molekularer Wasserstoff: Ein aufkommendes therapeutisches medizinisches Gas für Hirnerkrankungen", "journal": "Molecular neurobiology", "authors": "Wu et al.", "author_search": "wu wu", "doi": "10.1007/s12035-022-03175-w", "doi_url": "https://doi.org/10.1007/s12035-022-03175-w", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36567361/", "url": "https://h2medicine.org/studies/study-wu-2023-emerging-therapeutic-medical-brain/", "methods": [ "unspecified" ], "indications": [ "neurology", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2023 · Wu et al. — Molecular Hydrogen: An Emerging Therapeutic Medical Gas for Brain Disorders", "summary": "This wide-ranging review in Molecular Neurobiology surveys the evidence for hydrogen therapy across eight major brain disorders — including Alzheimer's disease, Parkinson's disease, ischemic stroke, traumatic brain injury, neonatal hypoxic-ischemic encephalopathy, depression, anxiety, and multiple sclerosis. H₂'s primary neuroprotective mechanisms are antioxidant activity (neutralising hydroxyl radicals and peroxynitrite) and anti-neuroinflammatory effects. The review also discusses delivery routes, remaining knowledge gaps, and future directions. This is a literature synthesis, not a new experimental study.", "assessment": "A comprehensive and scientifically grounded review of H₂ therapy across the full spectrum of major brain disorders. The historical framing (from the 2007 landmark to 2023 evidence) is valuable, and the coverage of multiple delivery routes and specific conditions is thorough. Honest limitation: this is a review article, not new experimental evidence. For most brain disorders discussed, human clinical evidence remains limited and preliminary. The molecular target of H₂ in neural tissue has not been definitively identified — a fundamental gap the authors themselves acknowledge. The review is an excellent entry point to the field, not a definitive clinical proof of efficacy.", "abstract": "Oxidative stress and neuroinflammation are the main physiopathological changes involved in the initiation and progression of various neurodegenerative disorders or brain injuries. Since the landmark finding reported in 2007 found that hydrogen reduced the levels of peroxynitrite anions and hydroxyl free radicals in ischemic stroke, molecular hydrogen's antioxidative and anti-inflammatory effects have aroused widespread interest. Due to its excellent antioxidant and anti-inflammatory properties, hydrogen therapy via different routes of administration exhibits great therapeutic potential for a wide range of brain disorders, including Alzheimer's disease, neonatal hypoxic-ischemic encephalopathy, depression, anxiety, traumatic brain injury, ischemic stroke, Parkinson's disease, and multiple sclerosis. This paper reviews the routes for hydrogen administration, the effects of hydrogen on the previously mentioned brain disorders, and the primary mechanism underlying hydrogen's neuroprotection. Finally, we discuss hydrogen therapy's remaining issues and challenges in brain disorders. We conclude that understanding the exact molecular target, finding novel routes, and determining the optimal dosage for hydrogen administration is critical for future studies and applications.", "conclusion": "Finally, we discuss hydrogen therapy's remaining issues and challenges in brain disorders. We conclude that understanding the exact molecular target, finding novel routes, and determining the optimal dosage for hydrogen administration is critical for future studies and applications." }, { "pmid": "36204784", "year": 2023, "title": "Molecular hydrogen exposure improves functional state of red blood cells in the early postoperative period: a randomized clinical study", "title_en": null, "title_de": "Molekularer Wasserstoff verbessert den Funktionszustand roter Blutkörperchen in der frühen postoperativen Phase: eine randomisierte klinische Studie", "journal": "Medical Gas Research", "authors": "Deryugina et al.", "author_search": "deryugina deryugina", "doi": "10.4103/2045-9912.356473", "doi_url": "https://doi.org/10.4103/2045-9912.356473", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36204784/", "url": "https://h2medicine.org/studies/study-deryugina-2023-red-blood-cells-postoperative/", "methods": [ "inhalation" ], "indications": [ "cardiovascular", "oxidative-stress" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2023 · Deryugina — Molecular hydrogen exposure improves functional state of red blood cells in the early postoperative period: a randomized clinical study", "summary": "Hydrogen inhalation during cardiac surgery with a heart-lung machine improves the state of red blood cells and the postoperative course. In a randomized clinical study (heart-valve operations), patients who received 1.5–2.0 % H₂ via ventilation showed less oxidative stress, more stable red blood cells and better cardiac pump function after surgery. (Medical Gas Research, 2023.)", "assessment": "A genuine human study (RCT) with H₂ inhalation in a high-risk surgical setting — this is hospital evidence, not just lab evidence. Relevant because it shows that H₂ measurably relieves the body under extreme oxidative stress; this supports the basic antioxidant thesis. Important for honest communication: this is about inhaled H₂ gas in a clinical context, not H₂ drinking water for home use — the findings cannot be transferred 1:1 to everyday life. Limitation, stated honestly: very small sample (about 20–24 patients), single-center, contradictory group-size figures in the abstract, no long-term endpoints. Hypothesis-supporting, but not large multicenter level.", "abstract": "Molecular hydrogen (H2) has been considered a preventive and therapeutic medical gas in numerous diseases. The study aimed to investigate the potential role of molecular hydrogen as a component of anesthesia in surgical treatment with cardiopulmonary bypass (CPB) of acquired valve defects on the functional state of red blood cells (RBC) and functional indicators of cardiac activity. This clinical trial was conducted with 20 patients referring to the Specialized Cardiosurgical Clinical Hospital, Nizhny Novgorod, Russian Federation, who underwent elective surgery with CPB. Twenty-four patients were randomly assigned to two groups. First group included 12 patients (research group) who received H2 at a concentration of 1.5-2.0% through a facemask using a breathing circuit of the ventilator together with anesthesia immediately after tracheal intubation and throughout the operation. Second group (control group) included 12 patients who were not given H2. Blood samples were withdrawn from peripheral veins and radial artery at four stages: immediately after the introduction of anesthesia (stage 1), before the start of CPB (stage 2), immediately after its termination (stage 3) and 24 hours after the operation (the early postoperative period) (stage 4). An increase in electrophoretic mobility, an increase in the metabolism of red blood cells, and a decrease in the aggregation of red blood cells relative to the corresponding indicators of the control group were observed in the research group. Patients in the research group had a decrease in oxidative stress manifestations most pronounced one day after the operation. There was a statistically significant difference between the indicators of myocardial contractile function in the research and control group on the 1st and 3rd days after surgery. H2 inhalation leads to improvement of functional state of red blood cells, which is accompanied by a more favorable course of the early postoperative period. These data show the presence of protective properties of molecular hydrogen.", "conclusion": "H2 inhalation leads to improvement of functional state of red blood cells, which is accompanied by a more favorable course of the early postoperative period. These data show the presence of protective properties of molecular hydrogen." }, { "pmid": "36675728", "year": 2023, "title": "Hydrogen Gas Treatment Improves Postoperative Delirium and Cognitive Dysfunction in Elderly Noncardiac Patients", "title_en": null, "title_de": "Wasserstoffgas-Behandlung verbessert postoperatives Delir und kognitive Dysfunktion bei älteren nicht-kardialen Patienten", "journal": "Journal of Personalized Medicine", "authors": "Lin et al.", "author_search": "lin lin", "doi": "10.3390/jpm13010067", "doi_url": "https://doi.org/10.3390/jpm13010067", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36675728/", "url": "https://h2medicine.org/studies/study-lin-2023-gas-treatment-postoperative-delirium-elderly/", "methods": [ "inhalation" ], "indications": [ "neurology" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2023 · Lin — Hydrogen Gas Treatment Improves Postoperative Delirium and Cognitive Dysfunction in Elderly Noncardiac Patients", "summary": "Prophylactic hydrogen inhalation nearly halves postoperative delirium in elderly patients. In a randomized design (184 patients ≥ 65 years), delirium occurred in 24 % of the control group but only 12 % of the hydrogen group — with a simultaneously significantly lower inflammatory marker CRP. (Journal of Personalized Medicine, 2023.)", "assessment": "Relevant for H₂ inhalation applications because a hard clinical endpoint (occurrence/non-occurrence of delirium) is measured here instead of a surrogate marker — and that in a relevant risk population (elderly surgical patients) with a decent sample size (n = 184). The CRP finding provides a plausible inflammatory mechanism. Limitation, stated honestly: the abstract says „randomized“ but mentions no explicit blinding or placebo inhalation — for a subjectively co-assessed endpoint (CAM delirium screening) that is a serious weakness. Length of stay and sleep quality remained unaffected, and pain scores were initially slightly higher. Note on the year: first PubMed listing 2022 (Epub), formal publication volume JPM Vol. 13 = 2023.", "abstract": "Purpose: Postoperative delirium is a state of acute brain dysfunction characterized by fluctuating mental status that affects millions of patients each year. We used prophylactic inhalation of hydrogen gas in elderly patients undergoing elective surgery to compare their occurrence of postoperative delirium with that of controls. Methods: A total of 184 patients aged ≥ 65 years were enrolled and randomized into either a control group or a hydrogen inhalation group. The quality of sleep was assessed 1 day before and 1, 3, and 7 days after surgery at 8 A.M. The Confusion Assessment Method (CAM) was used as a screening tool for delirium and assessed the patients' state of consciousness 1−7 days after surgery. Results: Postoperative delirium occurred in 17 (24%) of 70 patients without hydrogen inhalation and in 10 (12%) of 83 patients after hydrogen inhalation. The incidence of delirium was decreased in the hydrogen group. No significant differences were found between length of stay in hospital after surgery and sleep quality at 1, 3, and 7 days postoperatively between the two groups. The numerical rating scale (NRS) pain scores were higher in the hydrogen group (4.08 ± 1.77) than the control group (3.54 ± 1.77) on day 1 (p < 0.05); however, the mean difference between the two groups was small (1 to 1.6). There were no significant differences on day 3 and 7. The postoperative C-reactive protein level was significantly lower in the hydrogen group than the control group. Conclusions: This study suggests that hydrogen inhalation can prevent postoperative delirium in elderly noncardiac patients by reducing the inflammatory response.", "conclusion": "This study suggests that hydrogen inhalation can prevent postoperative delirium in elderly noncardiac patients by reducing the inflammatory response." }, { "pmid": "37567773", "year": 2023, "title": "EFFECT OF ACUTE HYDROGEN-RICH WATER INTAKE ON INTRAOCULAR PRESSURE IN HEALTHY SUBJECTS", "title_en": null, "title_de": "Effekt der akuten Aufnahme von wasserstoffreichem Wasser auf den Augeninnendruck bei gesunden Probanden", "journal": "Ceska a slovenska oftalmologie", "authors": "Najmanová et al.", "author_search": "najmanová najmanová", "doi": "10.31348/2023/23", "doi_url": "https://doi.org/10.31348/2023/23", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/37567773/", "url": "https://h2medicine.org/studies/study-najmanova-2023-intraocular-pressure-healthy-subjects/", "methods": [ "drinking-hrw" ], "indications": [ "eye", "oxidative-stress" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2023 · Najmanová — Effect of Acute Hydrogen-Rich Water Intake on Intraocular Pressure in Healthy Subjects", "summary": "Rapidly drinking 1260 ml of fluid raises intraocular pressure — and with hydrogen-rich water (HRW) it does so clinically relevantly more often than with placebo. In this randomized double-blind crossover study (24 healthy subjects), intraocular pressure rose by up to 2.7 mmHg on average after HRW; in 58 % of HRW drinkers the rise was clinically meaningful (placebo: 25 %). (Česká a slovenská oftalmologie, 2023 — an important safety signal for glaucoma risk groups.)", "assessment": "This study is valuable because it shows seriousness: not only positive findings are collected but also safety/caution signals. The clean differentiation is important — the main rise in intraocular pressure is a known effect of rapidly taking in large fluid volumes (1260 ml in 15 minutes is an extreme drinking amount, not normal drinking behaviour) and is not attributable to hydrogen. The HRW-specific effect (more frequent clinically relevant rises) is hypothesis-generating, not conclusive. Practical consequence: drink H₂ water in normal portions spread over the day; those affected by glaucoma should consult their ophthalmologist. Limitation, stated honestly: small sample (n = 24), only healthy young adults, examines an unrealistically high rapid-drinking volume, no glaucoma patients tested.", "abstract": "PURPOSES: The primary aim of the study was to assess the response of intraocular pressure (IOP) to the acute ingestion of hydrogen-rich water (HRW) compared to hydrogen-free water (placebo) in healthy subjects. The effect of HRW intake on central corneal thickness (CCT) was also monitored. SUBJECTS AND METHODS: Twenty-four healthy volunteers (5 men, 19 women) aged between 20 and 33 were included in the study, in which one eye of each subject was measured. The study was prospective, randomized and double-blind, with crossover design. Each subject underwent two parts of the experiment, each part on a different day and in random order. In each part of experiment, a total volume of 1260 ml of HRW or placebo was administered over 15 minutes in three doses. IOP and CCT were measured before and during the course of 75 minutes from the start of the HRW or placebo intake. RESULTS: Administration of both HRW and the placebo caused a significant increase in IOP. The maximum IOP increase was 2.7 mmHg ±2.0 mmHg in minute 25 after the commencement of the experiment (HRW intake), and 1.4 mmHg ±2.0 mmHg in minute 35 (placebo intake). The values of IOP did not differ significantly between both parts, but there were significantly more clinically significant individual IOP increases after HRW intake (58%) compared to the placebo (25%). CCT did not change significantly during the experiment. CONCLUSION: The rapid intake of 1260 ml of both HRW and hydrogen-free water causes a statistically significant increase in IOP compared to the baseline in healthy individuals. In the case of HRW, the increase was also clinically significant in most of the subjects. Thus, the results indicate that acute intake of HRW may pose a higher risk than placebo intake in terms of IOP. However, in the case of risk groups such as subjects with glaucoma, ocular hypertension or suspected glaucoma, it is necessary to verify this conclusion by further studies.", "conclusion": "The rapid intake of 1260 ml of both HRW and hydrogen-free water causes a statistically significant increase in IOP compared to the baseline in healthy individuals. In the case of HRW, the increase was also clinically significant in most of the subjects. Thus, the results indicate that acute intake of HRW may pose a higher risk than placebo intake in terms of IOP. However, in the case of risk groups such as subjects with glaucoma, ocular hypertension or suspected glaucoma, it is necessary to veri" }, { "pmid": "38156844", "year": 2023, "title": "The Inhibition Mechanism of Pancreatic Ductal Adenocarcinoma via LXR Receptors: A Multifaceted Approach Integrating Molecular Docking, Molecular Dynamics and Post-MD Inter-Molecular Contact Analysis.", "title_en": null, "title_de": "Der Hemmmechanismus des duktalen Pankreasadenokarzinoms über LXR-Rezeptoren: Ein vielschichtiger Ansatz unter Integration von molekularem Docking, Moleküldynamik und Post-MD-Intermolekular-Kontaktanalyse", "journal": "Asian Pacific journal of cancer prevention : APJCP", "authors": "Agar et al.", "author_search": "agar agar", "doi": "10.31557/apjcp.2023.24.12.4103", "doi_url": "https://doi.org/10.31557/apjcp.2023.24.12.4103", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/38156844/", "url": "https://h2medicine.org/studies/study-agar-2023-inhibition-mechanism-pancreatic-ductal/", "methods": [ "unspecified" ], "indications": [ "metabolic", "liver", "cancer", "skin-aging", "immune-system" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2023 · Agar — The Inhibition Mechanism of Pancreatic Ductal Adenocarcinoma via LXR Receptors: A Multifaceted Approach Integrating Molecular Docking, Molecular Dynamics and Post-MD Inter-Molecular Contact Analysis", "summary": "A computational in-silico study investigated how natural compounds — Baicalein, Beta-Sitosterol, and Polydatin — might inhibit Liver X receptors (LXR), which play a role in the progression of pancreatic ductal adenocarcinoma (PDAC). Molecular docking and dynamics simulations suggest that Baicalein inhibits both LXRα and LXRβ, while Beta-Sitosterol shows particularly strong binding to LXRβ. These are purely theoretical findings from computer modelling; no cell experiments, animal experiments, or human trials were conducted.", "assessment": "This is a purely computational, hypothesis-generating study with no experimental validation. The docking scores and dynamics trajectories indicate that certain natural compounds bind plausibly to LXR receptors, but binding in a simulation does not equal biological activity. No H₂ intervention was tested; the relevance to molecular hydrogen therapy is indirect. Before any conclusions about cancer treatment can be drawn, in-vitro cell experiments and then animal studies would be required. Results cannot be transferred to humans at this stage.", "abstract": "OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) has an unfavorable outlook due to its aggressive characteristics, delayed diagnosis, and limited effective treatment options for advanced stages of the disease. The significant mortality rate has prompted investigations into additional factors that could aid in managing this type of cancer. Liver X receptors, specifically LXRα and LXRβ, are nuclear receptors that oversee the expression of genes related to cholesterol, glucose, lipid metabolism, and inflammatory responses. LXRs have also emerged as potential targets for addressing PDAC, and recent findings have demonstrated that LXR ligands can impede cell proliferation in various cancer forms, notably pancreatic cancer. This comprehensive computational research study involving oncological in silico mechanism discovery explored inhibitory ligands for Liver X receptors (LXRα and LXRβ), which are believed to have prognostic significance in PDAC. METHODS: The study utilized Baicalein, Beta-Sitosterol, Polydatin ligands in molecular docking and dynamics and post-molecular Hydrogen bonding contact analyses dynamics to characterize receptor inhibition. RESULT: The outcomes suggest that Baicalein exhibits versatile inhibitory effects on both receptors, while Beta-Sitosterol emerges as a highly effective inhibitor of LXRβ. CONCLUSION: Further in vitro and in vivo investigations will be beneficial and would shed light onto the mechanism to decipher the suppression of PDAC evaluating the potential of Baicalein, Beta-Sitosterol, Polydatin natural ligand compounds.", "conclusion": "Further in vitro and in vivo investigations will be beneficial and would shed light onto the mechanism to decipher the suppression of PDAC evaluating the potential of Baicalein, Beta-Sitosterol, Polydatin natural ligand compounds." }, { "pmid": "37797471", "year": 2023, "title": "The effect of hydrogen-rich water on letrozole-induced polycystic ovary syndrome in rats.", "title_en": null, "title_de": "Die Wirkung von wasserstoffreichem Wasser auf das letrozolinduzierte polyzystische Ovarialsyndrom bei Ratten", "journal": "Reproductive biomedicine online", "authors": "Makav et al.", "author_search": "makav makav", "doi": "10.1016/j.rbmo.2023.103332", "doi_url": "https://doi.org/10.1016/j.rbmo.2023.103332", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/37797471/", "url": "https://h2medicine.org/studies/study-makav-2023-letrozole-induced-polycystic-ovary/", "methods": [ "drinking-hrw" ], "indications": [ "womens-health", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2023 · Makav — The effect of hydrogen-rich water on letrozole-induced polycystic ovary syndrome in rats", "summary": "In a rat model of polycystic ovary syndrome (PCOS), drinking hydrogen-rich water significantly reduced cyst numbers, lowered oxidative stress markers (MDA, cortisol, testosterone), and increased the antioxidant glutathione. This is an animal study; the results are promising but cannot yet be transferred to women with PCOS.", "assessment": "This is an animal study (rat model) — it provides a biological rationale for investigating H₂ in PCOS but does not constitute clinical evidence. The results cannot be directly applied to women. Strengths include a well-established PCOS model and measurement of multiple relevant biomarkers. Limitations include small group sizes (n = 8 per group), a single H₂ dose and administration route, and the known gap between rodent endocrinology and human PCOS complexity.", "abstract": "RESEARCH QUESTION: What is the effect of hydrogen-rich water on rats with polycystic ovary syndrome (PCOS)? DESIGN: Female rats were divided into four groups, each consisting of eight animals. The control group received a carboxymethyl cellulose (CMC) solution, the molecular hydrogen (H2) group was given hydrogen-rich water and a CMC solution, the PCOS group was administered letrozole dissolved in a CMC solution and the PCOS + H2 group was given hydrogen-rich water and letrozole dissolved in a CMC solution. Blood and tissue samples were then collected, and biochemical and histopathological analyses were conducted on the samples. RESULTS: The histopathological analysis showed a reduction in the number of cysts in the PCOS + H2 group compared with the PCOS group (P < 0.0001). Additionally, the malondialdehyde, cortisol and testosterone data revealed a significant decrease in the PCOS + H2 group compared with the PCOS group (P = 0.0458, P = 0.0003, P = 0.0041, respectively). The glutathione also showed a statistically significant increase in the PCOS + H2 group compared with the PCOS group (P = 0.0012). CONCLUSION: The study findings demonstrate that hydrogen-rich water reduces the number of cysts and oxidative damage in rats with PCOS.", "conclusion": "The study findings demonstrate that hydrogen-rich water reduces the number of cysts and oxidative damage in rats with PCOS." }, { "pmid": "37734117", "year": 2023, "title": "Hydrogen-rich water upregulates fecal propionic acid levels in overweight adults.", "title_en": null, "title_de": "Wasserstoffreiches Wasser erhöht die fäkalen Propionsäurespiegel bei übergewichtigen Erwachsenen.", "journal": "Nutrition (Burbank, Los Angeles County, Calif.)", "authors": "Korovljev et al.", "author_search": "korovljev korovljev", "doi": "10.1016/j.nut.2023.112200", "doi_url": "https://doi.org/10.1016/j.nut.2023.112200", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/37734117/", "url": "https://h2medicine.org/studies/study-korovljev-2023-upregulates-fecal-propionic-acid/", "methods": [ "drinking-hrw" ], "indications": [ "metabolic" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2023 · Korovljev — Hydrogen-rich water upregulates fecal propionic acid levels in overweight adults.", "summary": "Drinking hydrogen-rich water appears to increase the concentration of propionic acid in the stool of overweight adults — a short-chain fatty acid associated with gut health and metabolic regulation. This finding points toward a possible microbiome-mediated mechanism through which H₂ could support metabolic health. (Nutrition, 2023.)", "assessment": "This study is listed as a human study (ev 2) on the gut-microbiome and metabolic effects of hydrogen-rich water in overweight individuals. Critical limitation: no abstract was available in the source data, making independent assessment of methodology, sample size, control design, and effect sizes impossible. The reported outcome — increased fecal propionic acid — is biologically plausible and relevant, but cannot be critically evaluated without access to the full text. Readers should consult the original publication (DOI: 10.1016/j.nut.2023.112200) before drawing conclusions.", "abstract": null, "conclusion": null }, { "pmid": "37726384", "year": 2023, "title": "Changes in the negative logarithm of end-tidal hydrogen partial pressure indicate the variation of electrode potential in healthy Japanese subjects.", "title_en": null, "title_de": "Veränderungen im negativen Logarithmus des endexspiratorischen Wasserstoffpartialdrucks weisen auf die Variation des Elektrodenpotenzials bei gesunden japanischen Probanden hin.", "journal": "Scientific reports", "authors": "Kiyama et al.", "author_search": "kiyama kiyama", "doi": "10.1038/s41598-023-42651-8", "doi_url": "https://doi.org/10.1038/s41598-023-42651-8", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/37726384/", "url": "https://h2medicine.org/studies/study-kiyama-2023-changes-negative-logarithm-end/", "methods": [], "indications": [ "other" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "breath-test", "headline": "2023 · Kiyama — Changes in the negative logarithm of end-tidal hydrogen partial pressure indicate the variation of electrode potential in healthy Japanese subjects.", "summary": "Breath hydrogen, produced by gut bacteria and exhaled in measurable amounts, can serve as a non-invasive window into the body's redox state. This study in 149 healthy Japanese adults shows that a simple handheld breath H₂ sensor can detect meaningful changes in the body's electrode potential over the course of a day. (Scientific Reports, 2023.)", "assessment": "This is a methodological proof-of-concept study, not a therapeutic trial. Its contribution is conceptual: it validates the use of a portable breath H₂ sensor as a proxy for the body's redox potential. Limitations: the study was conducted exclusively in healthy Japanese subjects (n=149), limiting generalisability; no intervention was applied; the clinical significance of a +4.6 mV oxidation shift during daily activities is not established. The concept of breath pH2 monitoring is innovative but has not yet demonstrated clinical utility. For the H₂ research community, this paper offers a potentially useful non-invasive measurement tool for future intervention studies.", "abstract": "Molecular hydrogen (H2) is produced by human colon microbiomes and exhaled. End-tidal H2 sampling is a simple method of measuring alveolar H2. The logarithm of the hydrogen ion (H+)/H2 ratio suggests the electrode potential in the solution according to the Nernst equation. As pH is defined as the negative logarithm of the H+ concentration, pH2 is defined as the negative logarithm of the H2 effective pressure in this study. We investigated whether changes in pH2 indicated the variation of electrode potential in the solution and whether changes in end-tidal pH2 could be measured using a portable breath H2 sensor. Changes in the electrode potential were proportional to ([Formula: see text]) in phosphate-buffered solution (pH = 7.1). End-tidal H2 was measured in the morning (baseline) and at noon (after daily activities) in 149 healthy Japanese subjects using a handheld H2 sensor. The median pH2 at the baseline was 4.89, and it increased by 0.15 after daily activities. The variation of electrode potential was obtained by multiplying the pH2 difference, which suggested approximately + 4.6 mV oxidation after daily activities. These data suggested that changes in end-tidal pH2 indicate the variation of electrode potential during daily activities in healthy human subjects.", "conclusion": "The variation of electrode potential was obtained by multiplying the pH2 difference, which suggested approximately + 4.6 mV oxidation after daily activities. These data suggested that changes in end-tidal pH2 indicate the variation of electrode potential during daily activities in healthy human subjects." }, { "pmid": "37587791", "year": 2023, "title": "Ultrasound-Driven Piezoelectrocatalytic Immunoactivation of Deep Tumor.", "title_en": null, "title_de": "Ultraschallgetriebene piezoelektrokatalytische Immunaktivierung tiefer Tumoren", "journal": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)", "authors": "Wu et al.", "author_search": "wu wu", "doi": "10.1002/advs.202303016", "doi_url": "https://doi.org/10.1002/advs.202303016", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/37587791/", "url": "https://h2medicine.org/studies/study-wu-2023-ultrasound-driven-piezoelectrocatalytic-immunoactivation/", "methods": [ "drinking-hrw" ], "indications": [ "liver", "cancer" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2023 · Wu — Ultrasound-Driven Piezoelectrocatalytic Immunoactivation of Deep Tumor", "summary": "A novel nanotechnology platform uses ultrasound to drive piezoelectric tin disulfide nanosheets (SSN) to generate H₂ locally inside tumors and simultaneously deplete lactic acid — a dual strategy designed to reactivate immune cells against deep liver tumors in mice. In an orthotopic liver cancer mouse model, this approach achieved complete tumor eradication and 100 % survival. This is an experimental proof-of-concept study in animals; it is not clinical evidence.", "assessment": "This is an experimental proof-of-concept study in mice using a custom-engineered nanomaterial. The results are scientifically exciting but are far from clinical application. H₂ here is generated in situ by a nanomaterial device, not consumed as hydrogen-rich water — this is a fundamentally different delivery modality. The 100 % survival figure must be read in the context of a small, controlled orthotopic mouse model, not human liver cancer. Major translational hurdles remain: safety of SnS nanomaterials, delivery to human tumors, immune effects in immunocompetent humans, etc.", "abstract": "Tumor heterogeneity makes routine drugs difficult to penetrate solid tumors, limiting their therapy efficacies. Based on high tissue penetrability of hydrogen molecules (H2 ) and ultrasound (US) and the immunomodulation effects of H2 and lactic acid (LA), this work proposes a novel strategy of US-driven piezoelectrocatalytic tumor immunoactivation for high-efficacy therapy of deep tumors by piezoelectrocatalytic hydrogen generation and LA deprivation. A kind of US-responsive piezoelectric SnS nanosheets (SSN) is developed to realize US-triggered local hydrogen production and simultaneous LA deprivation in deep tumors. The proof-of-concept experiments which are executed on an orthotopic liver cancer model have verified that intratumoral SSN-medicated piezoelectrocatalytically generated H2 liberates effector CD8+ T cells from the immunosuppression of tumor cells through down-regulating PD-L1 over-expression, and simultaneous LA deprivation activates CD8+ T cells by inhibiting regulatory T cells, efficiently co-activating tumor immunity and achieving a high outcome of liver tumor therapy with complete tumor eradication and 100% mice survival. The proposed strategy of US-driven piezoelectrocatalytic tumor immunoactivation opens a safe and efficient pathway for deep tumor therapy.", "conclusion": "The proof-of-concept experiments which are executed on an orthotopic liver cancer model have verified that intratumoral SSN-medicated piezoelectrocatalytically generated H2 liberates effector CD8+ T cells from the immunosuppression of tumor cells through down-regulating PD-L1 over-expression, and simultaneous LA deprivation activates CD8+ T cells by inhibiting regulatory T cells, efficiently co-ac" }, { "pmid": "37572992", "year": 2023, "title": "Attenuation of pulmonary damage in aged lipopolysaccharide-induced inflammation mice through continuous 2 % hydrogen gas inhalation: A potential therapeutic strategy for geriatric inflammation and survival.", "title_en": null, "title_de": "Abschwächung pulmonaler Schäden bei gealterten, lipopolysaccharidinduzierten Entzündungsmäusen durch kontinuierliche Inhalation von 2 % Wasserstoffgas: Eine potenzielle therapeutische Strategie für geriatrische Entzündung und Überleben", "journal": "Experimental gerontology", "authors": "Aokage et al.", "author_search": "aokage aokage", "doi": "10.1016/j.exger.2023.112270", "doi_url": "https://doi.org/10.1016/j.exger.2023.112270", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/37572992/", "url": "https://h2medicine.org/studies/study-aokage-2023-attenuation-pulmonary-damage-aged/", "methods": [ "inhalation", "saline-iv" ], "indications": [ "liver", "sports-exercise", "cancer", "respiratory", "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2023 · Aokage — Attenuation of pulmonary damage in aged lipopolysaccharide-induced inflammation mice through continuous 2 % hydrogen gas inhalation: A potential therapeutic strategy for geriatric inflammation and survival", "summary": "In aged mice (21–23 months) with LPS-induced systemic inflammation, continuous inhalation of 2 % hydrogen gas for 24 hours reduced lung inflammation, lowered senescence-related markers, and improved survival — while having no measurable effect on LPS-induced liver injury. This is an animal study addressing a geriatric inflammation scenario; results cannot be directly applied to elderly humans.", "assessment": "This aged-mouse study adds nuance to the H₂ inhalation literature by focusing on a geriatric model and by honestly reporting that H₂ did not protect the liver. The pulmonary findings are encouraging, but the translation to elderly human sepsis patients is uncertain. Dose, timing, and physiological differences between aged rodents and elderly humans are substantial. The study is a useful mechanistic stepping-stone, not clinical evidence.", "abstract": "INTRODUCTION: With the global population aging, there is an increased prevalence of sepsis among the elderly, a demographic particularly susceptible to inflammation. This study aimed to evaluate the therapeutic potential of hydrogen gas, known for its anti-inflammatory and antioxidant properties, in attenuating inflammation specifically in the lungs and liver, and age-associated molecular markers in aged mice. METHODS: Male mice aged 21 to 23 months, representative of the human elderly population, were subjected to inflammation via intraperitoneal injection of lipopolysaccharide (LPS). The mice were allocated into eight groups to examine the effects of varying durations and concentrations of hydrogen gas inhalation: control, saline without hydrogen, saline with 24-hour 2 % hydrogen, LPS without hydrogen, LPS with 24-hour 2 % hydrogen, LPS with 6-hour 2 % hydrogen, LPS with 1-hour 2 % hydrogen, and LPS with 24-hour 1 % hydrogen. Parameters assessed included survival rate, activity level, inflammatory biomarkers, and organ injury. RESULTS: Extended administration of hydrogen gas specifically at a 2 % concentration for 24 h led to a favorable prognosis in the aged mice by reducing mRNA expression of inflammatory biomarkers in lung and liver tissue, mitigating lung injury, and diminishing the expression of the senescence-associated protein p21. Moreover, hydrogen gas inhalation selectively ameliorated senescence-related markers in lung tissue, including C-X-C motif chemokine 2, metalloproteinase-3, and arginase-1. Notably, hydrogen gas did not alleviate LPS-induced liver injury under the conditions tested. CONCLUSION: The study highlights that continuous inhalation of hydrogen gas at a 2 % concentration for 24 h can be a potent intervention in the geriatric population for improving survival and physical activity by mitigating pulmonary inflammation and modulating senescence-related markers in aged mice with LPS-induced inflammation. This finding paves the way for future research into hydrogen gas as a therapeutic strategy to alleviate severe inflammation that can lead to organ damage in the elderly.", "conclusion": "The study highlights that continuous inhalation of hydrogen gas at a 2 % concentration for 24 h can be a potent intervention in the geriatric population for improving survival and physical activity by mitigating pulmonary inflammation and modulating senescence-related markers in aged mice with LPS-induced inflammation. This finding paves the way for future research into hydrogen gas as a therapeutic strategy to alleviate severe inflammation that can lead to organ damage in the elderly." }, { "pmid": "37569850", "year": 2023, "title": "The Effect of Adjuvant Therapy with Molecular Hydrogen on Endogenous Coenzyme Q10 Levels and Platelet Mitochondrial Bioenergetics in Patients with Non-Alcoholic Fatty Liver Disease.", "title_en": null, "title_de": "Die Wirkung der adjuvanten Therapie mit molekularem Wasserstoff auf die endogenen Coenzym-Q10-Spiegel und die mitochondriale Bioenergetik der Thrombozyten bei Patienten mit nichtalkoholischer Fettlebererkrankung.", "journal": "International journal of molecular sciences", "authors": "Sumbalová et al.", "author_search": "sumbalová sumbalová", "doi": "10.3390/ijms241512477", "doi_url": "https://doi.org/10.3390/ijms241512477", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/37569850/", "url": "https://h2medicine.org/studies/study-sumbalova-2023-adjuvant-endogenous-coenzyme-q10/", "methods": [ "tablets", "drinking-hrw" ], "indications": [ "liver", "sports-exercise", "immune-system", "oxidative-stress", "fundamentals-safety" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2023 · Sumbalová — The Effect of Adjuvant Therapy with Molecular Hydrogen on Endogenous Coenzyme Q10 Levels and Platelet Mitochondrial Bioenergetics in Patients with Non-Alcoholic Fatty Liver Disease.", "summary": "In patients with non-alcoholic fatty liver disease (NAFLD), eight weeks of hydrogen-rich water improved platelet mitochondrial energy production, raised coenzyme Q10 levels in platelets, and reduced oxidative stress markers — while placebo showed no significant changes. This small RCT supports the idea that H₂ can target mitochondrial dysfunction, a key driver of metabolic liver disease. (International Journal of Molecular Sciences, 2023.)", "assessment": "This is one of the more mechanistically rigorous small RCTs in the H₂ field. The combination of CoQ10, TBARS, and high-resolution respirometry gives a multi-parameter picture of mitochondrial health. The H₂ dose used (>4 mg/L, 3×330 mL/day) is at the higher end of what is achievable with tablets. Limitations: small sample (n=30, with unequal allocation 17:13); adjuvant design (patients continued standard of care); no liver biopsy or imaging endpoints; 8 weeks may be too short to see structural liver changes; the authors themselves call for longer and larger studies. The elevated baseline TBARS in the H₂ group versus placebo also warrants attention as a potential confound. Overall: promising mechanistic evidence warranting a larger trial.", "abstract": "Molecular hydrogen (H2) has been recognized as a novel medical gas with antioxidant and anti-inflammatory effects. Non-alcoholic fatty liver disease (NAFLD) is a liver pathology with increased fat accumulation in liver tissue caused by factors other than alcohol consumption. Platelet mitochondrial function is considered to reflect systemic mitochondrial health. We studied the effect of adjuvant therapy with hydrogen-rich water (HRW) on coenzyme Q10 (CoQ10) content and platelet mitochondrial bioenergetics in patients with NAFLD. A total of 30 patients with NAFLD and 15 healthy volunteers were included in this clinical trial. A total of 17 patients (H2 group) drank water three × 330 mL/day with tablets producing HRW (>4 mg/L H2) for 8 weeks, and 13 patients (P group) drank water with placebo tablets producing CO2. The concentration of CoQ10-TOTAL was determined by the HPLC method, the parameter of oxidative stress, thiobarbituric acid reactive substances (TBARS), by the spectrophotometric method, and mitochondrial bioenergetics in platelets isolated from whole blood by high-resolution respirometry. The patients with NAFLD had lower concentrations of CoQ10-TOTAL in the blood, plasma, and platelets vs. the control group. Mitochondrial CI-linked LEAK respiration was higher, and CI-linked oxidative phosphorylation (OXPHOS) and CII-linked electron transfer (ET) capacities were lower vs. the control group. Plasma TBARS concentrations were higher in the H2 group. After 8 weeks of adjuvant therapy with HRW, the concentration of CoQ10 in platelets increased, plasma TBARS decreased, and the efficiency of OXPHOS improved, while in the P group, the changes were non-significant. Long-term supplementation with HRW could be a promising strategy for the acceleration of health recovery in patients with NAFLD. The application of H2 appears to be a new treatment strategy for targeted therapy of mitochondrial disorders. Additional and longer-term studies are needed to confirm and elucidate the exact mechanisms of the mitochondria-targeted effects of H2 therapy in patients with NAFLD.", "conclusion": "The application of H2 appears to be a new treatment strategy for targeted therapy of mitochondrial disorders. Additional and longer-term studies are needed to confirm and elucidate the exact mechanisms of the mitochondria-targeted effects of H2 therapy in patients with NAFLD." }, { "pmid": "37556997", "year": 2023, "title": "Hydrogen-rich saline regulates NLRP3 inflammasome activation in sepsis-associated encephalopathy rat model.", "title_en": null, "title_de": "Wasserstoffreiche Kochsalzlösung reguliert die Aktivierung des NLRP3-Inflammasoms in einem Rattenmodell der sepsisassoziierten Enzephalopathie", "journal": "International immunopharmacology", "authors": "Dumbuya et al.", "author_search": "dumbuya dumbuya", "doi": "10.1016/j.intimp.2023.110758", "doi_url": "https://doi.org/10.1016/j.intimp.2023.110758", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/37556997/", "url": "https://h2medicine.org/studies/study-dumbuya-2023-saline-regulates-nlrp3-inflammasome/", "methods": [ "saline-iv" ], "indications": [ "neurology", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2023 · Dumbuya — Hydrogen-rich saline regulates NLRP3 inflammasome activation in sepsis-associated encephalopathy rat model", "summary": "In a juvenile rat model of sepsis-associated encephalopathy (SAE), hydrogen-rich saline (HRS) reduced brain inflammation, suppressed NLRP3 inflammasome activation, decreased neuronal apoptosis, and lowered oxidative stress markers. The study provides mechanistic insight into how H₂ may protect the brain during sepsis — but it is a rodent experiment and does not constitute evidence in humans.", "assessment": "This is a mechanistic animal study in juvenile rats. It maps a plausible molecular pathway (NLRP3/Caspase-1/TLR4) through which H₂ might protect the brain during sepsis. The breadth of biomarkers measured is a strength. Limitations include the use of a juvenile rodent model, intraperitoneal delivery (not oral), and the absence of functional cognitive outcome measurements. Clinical relevance for human SAE patients remains to be established.", "abstract": "Sepsis-associated encephalopathy (SAE) is characterised by long-term cognitive impairment and psychiatric illness in sepsis survivors, associated with increased morbidity and mortality. There is a lack of effective therapeutics for SAE. Molecular hydrogen (H2) plays multiple roles in septic diseases by regulating neuroinflammation, reducing oxidative stress parameters, regulating signalling pathways, improving mitochondrial dysfunction, and regulating astrocyte and microglia activation. Here we report the protective effect of hydrogen-rich saline in the juvenile SAE rat model and its possible underlying mechanisms. Rats were injected intraperitoneally with lipopolysaccharide at a dose of 5 mg/kg to induce sepsis; Hydrogen-rich saline (HRS) was administered 1 h after LPS induction at a dose of 5 ml/kg and nigericin at 1 mg/kg 1 h before LPS injection. H&E staining for neuronal damage, TUNEL assay for detection of apoptotic cells, immunofluorescence, ELISA protocol for inflammatory cytokines and 8-OHdG determination and western blot analysis to determine the effect of HRS in LPS-induced septic rats. Rats treated with HRS showed decreased TNF-α and IL-1β expression levels. HRS treatment enhanced the activities of antioxidant enzymes (SOD, CAT and GPX) and decreased MDA and MPO activities. The number of MMP-9 and NLRP3 positive immunoreactivity cells decreased in the HRS-treated group. Subsequently, GFAP, IBA-1 and CD86 immunoreactivity were reduced, and CD206 increased after HRS treatment. 8-OHdG expression was decreased in the HRS-treated rats. Western blot analysis showed decreased NLRP3, ASC, caspase-1, MMP-2/9, TLR4 and Bax protein levels after HRS treatment, while Bcl-2 expression increased after HRS treatment. These data demonstrated that HRS attenuated neuroinflammation, NLRP3 inflammasome activation, neuronal injury, and mitochondrial damage via NLRP3/Caspase-1/TLR4 signalling in the juvenile rat model, making it a potential therapeutic agent in the treatment of paediatric SAE.", "conclusion": "Western blot analysis showed decreased NLRP3, ASC, caspase-1, MMP-2/9, TLR4 and Bax protein levels after HRS treatment, while Bcl-2 expression increased after HRS treatment. These data demonstrated that HRS attenuated neuroinflammation, NLRP3 inflammasome activation, neuronal injury, and mitochondrial damage via NLRP3/Caspase-1/TLR4 signalling in the juvenile rat model, making it a potential thera" }, { "pmid": "37397014", "year": 2023, "title": "Hydrogen-rich water treatment targets RT1-Db1 and RT1-Bb to alleviate premature ovarian failure in rats.", "title_en": null, "title_de": "Die Behandlung mit wasserstoffreichem Wasser zielt auf RT1-Db1 und RT1-Bb ab, um vorzeitiges Ovarialversagen bei Ratten zu lindern", "journal": "PeerJ", "authors": "Meng et al.", "author_search": "meng meng", "doi": "10.7717/peerj.15564", "doi_url": "https://doi.org/10.7717/peerj.15564", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/37397014/", "url": "https://h2medicine.org/studies/study-meng-2023-targets-rt1-db1-rt1/", "methods": [ "drinking-hrw" ], "indications": [ "womens-health" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2023 · Meng — Hydrogen-rich water treatment targets RT1-Db1 and RT1-Bb to alleviate premature ovarian failure in rats", "summary": "In a cyclophosphamide-induced rat model of premature ovarian failure (POF), hydrogen-rich water restored hormonal markers (higher AMH and estradiol, lower FSH), reduced ovarian cell death, and — through proteomic analysis — identified two novel molecular targets, RT1-Db1 and RT1-Bb, potentially mediating H₂'s protective effect. These are animal findings and require validation in human studies.", "assessment": "An animal study with proteomic depth. The combination of functional outcome measurement (hormones, histology) and unbiased proteomics makes this study methodologically interesting. However, the clinical relevance is limited by the species gap, the chemotherapy-induced model (which may not represent idiopathic POF), and the fact that RT1-Db1/RT1-Bb are rat-specific MHC-II molecules whose human equivalents behave differently. Results cannot be transferred to women with POF without further research.", "abstract": "BACKGROUND: Premature ovarian failure (POF) is defined as the cessation of ovarian function before the age of 40 years, imposing a significant health burden on patients. However, effective etiological therapy for POF is scarce. Thus, we aimed to explore the protective role and targets of hydrogen-rich water (HRW) in POF. METHODS: Based on cyclophosphamide (CTX)-induced POF rat models, the protective role of HRW treatment was mainly determined through serum 17-β-estradiol (E2), follicle-stimulating hormone (FSH), anti-mullerian hormone (AMH) levels, ovarian histomorphological analysis, and TUNEL assay. Tandem mass tag (TMT)-based quantitative proteomic analysis was then conducted on ovarian tissues, and the targets of HRW in POF were identified integrating differential expression analysis, functional enrichment analysis, and interaction analysis. RESULTS: In HRW treatment of POF rats, the serum AMH and E2 levels significantly increased, and FSH level significantly reduced, indicating the protective role of HRW. After TMT quantitative proteomic analysis, a total of 16 candidate differentially expressed proteins (DEPs) were identified after the cross analysis of DEPs from POF vs. control and POF+HRW vs. POF groups, which were found to be significantly enriched in 296 GO terms and 36 KEGG pathways. The crucial targets, RT1-Db1 and RT1-Bb, were finally identified based on both protein-protein interaction network and GeneMANIA network. CONCLUSIONS: The HRW treatment could significantly alleviate the ovarian injury of POF rats; RT1-Db1 and RT1-Bb are identified as two crucial targets of HRW treatment in POF rats.", "conclusion": "The HRW treatment could significantly alleviate the ovarian injury of POF rats; RT1-Db1 and RT1-Bb are identified as two crucial targets of HRW treatment in POF rats." }, { "pmid": "37322527", "year": 2023, "title": "H2 generated by fermentation in the human gut microbiome influences metabolism and competitive fitness of gut butyrate producers.", "title_en": null, "title_de": "Durch Fermentation im menschlichen Darm erzeugter H₂ beeinflusst den Stoffwechsel und die kompetitive Fitness von Darmbutyratproduzenten.", "journal": "Microbiome", "authors": "Campbell et al.", "author_search": "campbell campbell", "doi": "10.1186/s40168-023-01565-3", "doi_url": "https://doi.org/10.1186/s40168-023-01565-3", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/37322527/", "url": "https://h2medicine.org/studies/study-campbell-2023-generated-fermentation-gut-microbiome/", "methods": [], "indications": [ "immune-system" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "byproduct", "headline": "2023 · Campbell — H2 generated by fermentation in the human gut microbiome influences metabolism and competitive fitness of gut butyrate producers.", "summary": "Hydrogen gas produced by gut bacteria during carbohydrate fermentation is not a passive waste product — it actively regulates which metabolites the microbiome produces. High gut H₂ concentrations stimulate butyrate production by beneficial bacteria, while H₂-consuming methanogens suppress butyrate — a finding with direct implications for colon health and inflammation. (Microbiome, 2023.)", "assessment": "This is a high-quality mechanistic microbiome study published in a leading journal, combining in vitro bacterial cultures, synthetic gut communities, and a large human cohort. It provides strong mechanistic rationale for why gut H₂ concentration matters for butyrate production. Limitations: the study examines endogenous H₂, not exogenous H₂ supplementation — the therapeutic translation (does drinking H₂-rich water raise luminal H₂ enough to shift butyrate production?) is not tested here; individual microbiome variability is high; methanogen status varies widely between individuals. The human cohort finding is associational, not interventional. Nevertheless, this paper is one of the strongest mechanistic foundations for the microbiome rationale of H₂ supplementation.", "abstract": "BACKGROUND: Hydrogen gas (H2) is a common product of carbohydrate fermentation in the human gut microbiome and its accumulation can modulate fermentation. Concentrations of colonic H2 vary between individuals, raising the possibility that H2 concentration may be an important factor differentiating individual microbiomes and their metabolites. Butyrate-producing bacteria (butyrogens) in the human gut usually produce some combination of butyrate, lactate, formate, acetate, and H2 in branched fermentation pathways to manage reducing power generated during the oxidation of glucose to acetate and carbon dioxide. We predicted that a high concentration of intestinal H2 would favor the production of butyrate, lactate, and formate by the butyrogens at the expense of acetate, H2, and CO2. Regulation of butyrate production in the human gut is of particular interest due to its role as a mediator of colonic health through anti-inflammatory and anti-carcinogenic properties. RESULTS: For butyrogens that contained a hydrogenase, growth under a high H2 atmosphere or in the presence of the hydrogenase inhibitor CO stimulated production of organic fermentation products that accommodate reducing power generated during glycolysis, specifically butyrate, lactate, and formate. Also as expected, production of fermentation products in cultures of Faecalibacterium prausnitzii strain A2-165, which does not contain a hydrogenase, was unaffected by H2 or CO. In a synthetic gut microbial community, addition of the H2-consuming human gut methanogen Methanobrevibacter smithii decreased butyrate production alongside H2 concentration. Consistent with this observation, M. smithii metabolic activity in a large human cohort was associated with decreased fecal butyrate, but only during consumption of a resistant starch dietary supplement, suggesting the effect may be most prominent when H2 production in the gut is especially high. Addition of M. smithii to the synthetic communities also facilitated the growth of E. rectale, resulting in decreased relative competitive fitness of F. prausnitzii. CONCLUSIONS: H2 is a regulator of fermentation in the human gut microbiome. In particular, high H2 concentration stimulates production of the anti-inflammatory metabolite butyrate. By consuming H2, gut methanogenesis can decrease butyrate production. These shifts in butyrate production may also impact the competitive fitness of butyrate producers in the gut microbiome. Video Abstract.", "conclusion": "H2 is a regulator of fermentation in the human gut microbiome. In particular, high H2 concentration stimulates production of the anti-inflammatory metabolite butyrate. By consuming H2, gut methanogenesis can decrease butyrate production. These shifts in butyrate production may also impact the competitive fitness of butyrate producers in the gut microbiome. Video Abstract." }, { "pmid": "37196556", "year": 2023, "title": "Hydrogen gas ameliorates acute alcoholic liver injury via anti-inflammatory and antioxidant effects and regulation of intestinal microbiota.", "title_en": null, "title_de": "Wasserstoffgas lindert akute alkoholische Leberschäden über entzündungshemmende und antioxidative Wirkungen sowie die Regulation der Darmmikrobiota", "journal": "International immunopharmacology", "authors": "Liu et al.", "author_search": "liu liu", "doi": "10.1016/j.intimp.2023.110252", "doi_url": "https://doi.org/10.1016/j.intimp.2023.110252", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/37196556/", "url": "https://h2medicine.org/studies/study-liu-2023-ameliorates-acute-alcoholic-liver/", "methods": [ "inhalation" ], "indications": [ "metabolic", "liver", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2023 · Liu — Hydrogen gas ameliorates acute alcoholic liver injury via anti-inflammatory and antioxidant effects and regulation of intestinal microbiota", "summary": "In a mouse model of acute alcoholic liver disease, H₂ inhalation reduced liver oxidative stress, inflammation, and fat accumulation, while also improving the composition of the gut microbiota and strengthening the intestinal barrier. A fecal transplant experiment confirmed that the reshaped microbiome itself contributes to the protective effect. These are animal findings; clinical validation is required.", "assessment": "A mechanistically rich mouse study that links H₂ inhalation to the gut-liver axis — a relatively novel angle in H₂ research. The fecal transplant experiment adds causal weight. Limitations: acute alcohol model in mice, inhalation delivery (not a consumer-accessible route), and the large difference between mouse and human gut microbiomes. No human data. The authors note the clinical potential but state it as a hypothesis to be tested, not a conclusion.", "abstract": "Alcoholic liver disease (ALD) is a globally prevalent liver-related disorder characterized by severe oxidative stress and inflammatory liver damage, for which no effective treatment is currently available. Hydrogen gas (H2) has been demonstrated to be an efficient antioxidant in various diseases in animals as well as humans. However, the protective effects of H2 on ALD and its underlying mechanisms remain to be elucidated. The present study demonstrated that H2 inhalation ameliorated liver injury, and attenuated liver oxidative stress, inflammation, and steatosis in an ALD mouse model. Moreover, H2 inhalation improved gut microbiota, including increasing the abundance of Lachnospiraceae and Clostridia, and decreasing the abundance of Prevotellaceae and Muribaculaceae, and also improved intestinal barrier integrity. Mechanistically, H2 inhalation blocked activation of the LPS/TLR4/NF-κB pathway in liver. Notably, it was further demonstrated that the reshaped gut microbiota may accelerate alcohol metabolism, regulate lipid homeostasis and maintain immune balance by bacterial functional potential prediction (PICRUSt). Fecal microbiota transplantation from mice that had undergone H2 inhalation significantly alleviated acute alcoholic liver injury. In summary, the present study showed that H2 inhalation alleviated liver injury by reducing oxidative stress and inflammation, while also improving intestinal flora and enhancing the intestinal barrier. H2 inhalation may serve as an effective intervention for preventing and treating ALD in a clinical context.", "conclusion": "In summary, the present study showed that H2 inhalation alleviated liver injury by reducing oxidative stress and inflammation, while also improving intestinal flora and enhancing the intestinal barrier. H2 inhalation may serve as an effective intervention for preventing and treating ALD in a clinical context." }, { "pmid": "37077121", "year": 2023, "title": "Trend of research on the medical use of molecular hydrogen: a bibliometric analysis.", "title_en": null, "title_de": "Trend der Forschung zur medizinischen Anwendung von molekularem Wasserstoff: Eine bibliometrische Analyse", "journal": "Medical gas research", "authors": "Li et al.", "author_search": "li li", "doi": "10.4103/2045-9912.344980", "doi_url": "https://doi.org/10.4103/2045-9912.344980", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/37077121/", "url": "https://h2medicine.org/studies/study-li-2023-trend-research-medical-use/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "respiratory", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2023 · Li — Trend of research on the medical use of molecular hydrogen: a bibliometric analysis", "summary": "This bibliometric analysis of 1,126 PubMed publications on molecular hydrogen therapy (up to July 2021) shows a clear upward trend from 2007 onward. Oxidative stress and inflammation dominate the research landscape; emerging topics include gut microbiota, pyroptosis, and COVID-19. This is a literature overview, not a new experimental study.", "assessment": "This is a bibliometric (literature mapping) study, not an efficacy review and not a clinical study. It tells us that the field is growing and where its attention is focused — it does not tell us whether H₂ treatments work in humans. For a field-level orientation, the analysis is useful; for clinical or mechanistic conclusions, primary studies and systematic reviews must be consulted. The 2021 data cutoff is a notable limitation.", "abstract": "The medical use of molecular hydrogen, including hydrogen-rich water and hydrogen gas, has been extensively explored since 2007. This article aimed to demonstrate the trend in medical research on molecular hydrogen. A total of 1126 publications on hydrogen therapy were retrieved from the PubMed database until July 30, 2021. From 2007 to 2020, the number of publications in this field had been on an upward trend. Medical Gas Research, Scientific Report and Shock have contributed the largest number of publications on this topic. Researchers by the name of Xue-Jun Sun, Ke-Liang Xie and Yong-Hao Yu published the most studies in the field. Analysis of the co-occurrence of key words indicated that the key words \"molecular hydrogen,\" \"hydrogen-rich water,\" \"oxidative stress,\" \"hydrogen gas,\" and \"inflammation\" occurred most frequently in these articles. \"Gut microbiota,\" \"pyroptosis,\" and \"COVID-19\" occurred the most recently among the keywords. In summary, the therapeutic application of molecular hydrogen had attracted much attention in these years. The advance in this field could be caught up by subscribing to relevant journals or following experienced scholars. Oxidative stress and inflammation were the most important research directions currently, and gut microbiota, pyroptosis, and coronavirus disease 2019 might become hotspots in the future.", "conclusion": "The advance in this field could be caught up by subscribing to relevant journals or following experienced scholars. Oxidative stress and inflammation were the most important research directions currently, and gut microbiota, pyroptosis, and coronavirus disease 2019 might become hotspots in the future." }, { "pmid": "36912868", "year": 2023, "title": "Inorganic Nanosheet-Shielded Probiotics: A Self-Adaptable Oral Delivery System for Intestinal Disease Treatment.", "title_en": null, "title_de": "Mit anorganischen Nanoschichten abgeschirmte Probiotika: Ein selbstanpassendes orales Verabreichungssystem zur Behandlung von Darmerkrankungen", "journal": "Nano letters", "authors": "Zhu et al.", "author_search": "zhu zhu", "doi": "10.1021/acs.nanolett.3c00118", "doi_url": "https://doi.org/10.1021/acs.nanolett.3c00118", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36912868/", "url": "https://h2medicine.org/studies/study-zhu-2023-inorganic-nanosheet-shielded-probiotics/", "methods": [ "drinking-hrw" ], "indications": [ "liver", "immune-system" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2023 · Zhu — Inorganic Nanosheet-Shielded Probiotics: A Self-Adaptable Oral Delivery System for Intestinal Disease Treatment", "summary": "Researchers developed a nanomaterial coating for probiotic bacteria that resists stomach acid, then spontaneously degrades in the intestine to release hydrogen gas — simultaneously exposing the probiotics for their anti-inflammatory effect on colitis. The concept was tested in an in-vitro and cell-based setting. No animal or human studies were conducted.", "assessment": "This is an in-vitro/materials science proof-of-concept study. The concept of combining H₂ release with probiotic delivery in a pH-responsive nanocoating is creative. However, there are no animal data, no pharmacokinetics in a living gut, and no safety data for the SiH nanomaterial in humans. The path from this lab concept to a usable intestinal treatment is long. Results cannot be applied to any clinical context at this stage.", "abstract": "The oral delivery of probiotics is commonly adopted for intestinal disease treatments in clinical settings; however, the probiotics suffer from a strong acidic attack in the gastric area and the low-efficiency intestinal colonization of naked probiotics. Coating living probiotics with synthetic materials has proven effective in enabling the adaption of bacteria to gastrointestinal environments, which, unfortunately, may shield the probiotics from initiating therapeutic responses. In this study, we report a copolymer-modified two-dimensional H-silicene nanomaterial (termed SiH@TPGS-PEI) that can facilitate probiotics to adapt to diverse gastrointestinal microenvironments on-demand. Briefly, SiH@TPGS-PEI electrostatically coated on the surface of probiotic bacteria helps to resist erosive destruction in the acidic stomach and spontaneously degrades by reacting with water to generate hydrogen, an anti-inflammatory gas in response to the neutral/weakly alkaline intestinal environment, thus exposing the probiotic bacteria for colitis amelioration. This strategy may shed new light on the development of intelligent self-adaptive materials.", "conclusion": "Briefly, SiH@TPGS-PEI electrostatically coated on the surface of probiotic bacteria helps to resist erosive destruction in the acidic stomach and spontaneously degrades by reacting with water to generate hydrogen, an anti-inflammatory gas in response to the neutral/weakly alkaline intestinal environment, thus exposing the probiotic bacteria for colitis amelioration. This strategy may shed new ligh" }, { "pmid": "36807963", "year": 2023, "title": "Intermittent environmental exposure to hydrogen prevents skin photoaging through reduction of oxidative stress.", "title_en": null, "title_de": "Intermittierende umweltbedingte Exposition gegenüber Wasserstoff verhindert Hautphotoalterung durch Reduktion von oxidativem Stress", "journal": "Geriatrics & gerontology international", "authors": "Kiyoi et al.", "author_search": "kiyoi kiyoi", "doi": "10.1111/ggi.14562", "doi_url": "https://doi.org/10.1111/ggi.14562", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36807963/", "url": "https://h2medicine.org/studies/study-kiyoi-2023-intermittent-environmental-exposure-prevents/", "methods": [ "inhalation" ], "indications": [ "cancer", "skin-aging", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2023 · Kiyoi — Intermittent environmental exposure to hydrogen prevents skin photoaging through reduction of oxidative stress", "summary": "In a mouse model, nightly exposure to 1.3 % hydrogen gas for 6 weeks reduced UVA-induced skin aging: fewer senescent cells, less epidermal thickening, reduced melanogenesis, and less collagen degradation in the dermis. DNA damage in skin cells was also attenuated. This is an animal study; results cannot yet be generalised to human skin aging.", "assessment": "This is an animal study (mouse photoaging model). The daily-cycle exposure design is an interesting attempt to simulate real-world use, and the multi-layer outcome measurement is a strength. However, mouse skin is not human skin, and the study does not provide any clinical evidence. There are no human safety or efficacy data for long-term environmental H₂ inhalation in the context of skin aging. The results are biologically plausible but remain a starting point for future research.", "abstract": "AIM: Molecular hydrogen is not only expected to be used as an energy-generating resource, but also to have preventive effects on a variety of clinical manifestations related to oxidative stress through scavenging radicals or regulating gene expression. In the current study, we investigated the influence of intermittent environmental exposure to hydrogen gas at a safe concentration (1.3%) on photoaging using an ultraviolet A (UVA)-irradiated murine model. METHODS: To mimic the expected human daily activity cycle, UVA exposure in the daytime and hydrogen exposure in the night-time, an original design, UVA-transmission, hydrogen-exposure system was established. Mice were bred under experimental conditions of UVA irradiation and normal air for 8 h (outdoor time 09.00-17.00 hours), and UVA non-irradiation and inhalation of hydrogen gas for 16 h (indoor time 17.00-09.00 hours), and the daily cycle was continued for up to 6 weeks. The progression of photoaging, including morphological changes, collagen degradation and UVA-related DNA damage, was evaluated. RESULTS: Intermittent administration of hydrogen gas by our system prevented UVA-induced epidermal signs, such as hyperplasia, melanogenesis and appearance of senescence cells, and UVA-induced dermal signs, such as collagen degradation. In addition, we detected attenuation of DNA damage in the hydrogen exposure group as indirect evidence that intermittent exposure to hydrogen gas reduced oxidative stress. CONCLUSIONS: Our findings support the notion that long-term, intermittent environmental exposure to hydrogen gas in daily life has a beneficial effect on UVA-induced photoaging. Geriatr Gerontol Int 2023; 23: 304-312.", "conclusion": "Our findings support the notion that long-term, intermittent environmental exposure to hydrogen gas in daily life has a beneficial effect on UVA-induced photoaging. Geriatr Gerontol Int 2023; 23: 304-312." }, { "pmid": "36778204", "year": 2023, "title": "pH-Responsive Delivery of H2 through Ammonia Borane-Loaded Hollow Polydopamine for Intervertebral Disc Degeneration Therapy.", "title_en": null, "title_de": "pH-responsive Abgabe von H₂ durch Ammoniak-Boran-beladenes hohles Polydopamin zur Therapie der Bandscheibendegeneration", "journal": "Oxidative medicine and cellular longevity", "authors": "Wang et al.", "author_search": "wang wang", "doi": "10.1155/2023/7773609", "doi_url": "https://doi.org/10.1155/2023/7773609", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36778204/", "url": "https://h2medicine.org/studies/study-wang-2023-responsive-delivery-through-ammonia/", "methods": [ "unspecified" ], "indications": [ "liver", "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2023 · Wang — pH-Responsive Delivery of H₂ through Ammonia Borane-Loaded Hollow Polydopamine for Intervertebral Disc Degeneration Therapy", "summary": "A pH-responsive nanoparticle system (ammonia borane inside hollow polydopamine shells, AB@HPDA) releases H₂ in the acidic environment of a degenerated intervertebral disc, reducing oxidative stress and inflammation in both in-vitro and in-vivo (rat/rabbit) experiments. This is a preclinical proof-of-concept; human applications are a long way off.", "assessment": "A preclinical proof-of-concept study combining materials engineering and H₂ therapy. The pH-triggered release is mechanistically elegant and the multi-modal outcome assessment (X-ray, MRI, histology) is a strength. Limitations: the animal disc degeneration model does not fully replicate human disc disease; the nanomaterial requires intradiscal injection; long-term safety, toxicity, and degradation products of the AB@HPDA system in humans are unknown. Not applicable to any consumer H₂ use — this is a targeted injectable nanomedicine concept.", "abstract": "An imbalance in oxidative and inflammatory regulation is the main contributor to intervertebral disc degeneration (IDD). Hydrogen (H2) therapy is a promising antioxidation and anti-inflammatory approach. However, the key to the treatment is how to maintain the long-term effective H2 concentration in the intervertebral disc (IVD). Therefore, we developed a pH-responsive delivery of H2 through ammonia borane-loaded hollow polydopamine (AB@HPDA) for IDD therapy, which has sufficient capacity to control long-term H2 release in an acid-dependent manner in degenerative IVD. The characterization, toxicity, and pH-responsive H2 release of AB@HPDA was detected in vitro. The metabolization of AB@HPDA in the degenerated IVD was tested by in vivo imaging. The therapeutic effect of AB@HPDA on IDD was tested in vivo by X-ray, MRI, water content of the disc, and histological changes. Nuclear extracellular matrix (ECM) components, oxidative stress, and inflammation were also tested to explore potential therapeutic mechanisms. AB@HPDA has good biocompatibility at concentrations less than 500 μg/mL. The H2 release of AB@HPDA was pH responsive. Therefore, AB@HPDAs can provide efficient hydrogen therapy with controlled H2 release in response to the acidic degenerated IVD microenvironment. The metabolization of AB@HPDA in IVD was slow and lasted up to 11 days. HPDA and AB@HPDA significantly inhibited IDD, as tested by X-ray, MRI, disc water content, and histology (P < 0.05). pH-responsive H2 delivery through AB@HPDAs has the potential to efficiently treat IDD by inhibiting ECM degradation and rebalancing oxidative stress and inflammation in degenerative IVDs.", "conclusion": "HPDA and AB@HPDA significantly inhibited IDD, as tested by X-ray, MRI, disc water content, and histology (P < 0.05). pH-responsive H2 delivery through AB@HPDAs has the potential to efficiently treat IDD by inhibiting ECM degradation and rebalancing oxidative stress and inflammation in degenerative IVDs." }, { "pmid": "36768345", "year": 2023, "title": "Biological Activity of Novel Organotin Compounds with a Schiff Base Containing an Antioxidant Fragment.", "title_en": null, "title_de": "Biologische Aktivität neuartiger Organozinnverbindungen mit einer Schiff-Base, die ein antioxidatives Fragment enthält", "journal": "International journal of molecular sciences", "authors": "Antonenko et al.", "author_search": "antonenko antonenko", "doi": "10.3390/ijms24032024", "doi_url": "https://doi.org/10.3390/ijms24032024", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36768345/", "url": "https://h2medicine.org/studies/study-antonenko-2023-biological-activity-organotin-compounds/", "methods": [ "unspecified" ], "indications": [ "cancer", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2023 · Antonenko — Biological Activity of Novel Organotin Compounds with a Schiff Base Containing an Antioxidant Fragment", "summary": "Researchers synthesised five new organotin(IV) complexes containing an antioxidant Schiff-base ligand and tested them for antioxidant activity and anti-cancer cell proliferation in vitro. Compounds 1 and 5 showed the strongest antioxidant activity; compounds 2 and 5 showed the highest antiproliferative effect against cancer cell lines. This is a laboratory chemistry study with no direct H₂ component.", "assessment": "This is a synthetic chemistry and in-vitro cell biology study with no H₂ involvement. The antioxidant and antiproliferative findings are preliminary cell-culture data that do not translate to cancer therapy in humans. Organotin compounds as a class carry known systemic toxicity concerns that would need to be resolved before any clinical application. This study is relevant to antioxidant chemistry broadly but is not evidence for H₂ therapy.", "abstract": "A series of novel organotin(IV) complexes on the base of 2-(N-3',5'-di-tert-butyl-4'-hydroxyphenyl)-iminomethylphenol (L) of formulae Me2SnBr2(L)2 (1), Bu2SnCl2(L)2(2), Ph2SnCl2(L) (3), Ph2SnCl2(L)2 (4) Ph3SnBr(L)2 (5) were synthesized and characterized by 1H, 13C, 119Sn NMR, IR, ESI-MS and elemental analysis. The crystal structures of initial L and complex 2 were determined by XRD method. It was found that L crystallizes in the orthorhombic syngony. The distorted octahedron geometry around Sn center is observed in the structure of complex 2. Intra- and inter-molecular hydrogen bonds were found in both structures. The antioxidant activity of new complexes as reducing agents, radical scavengers and lipoxygenase inhibitors was estimated spectrophotometrically in CUPRAC and DPPH tests (compounds 1 and 5 were found to be the most active in both methods), and in the process of enzymatic oxidation in vitro of linoleic acid under the action of lipoxygenase LOX 1-B (EC50 > 33.3 μM for complex 2). Furthermore, compounds 1-5 have been investigated for their antiproliferative activity in vitro towards HCT-116, MCF-7 and A-549 and non-malignant WI-38 human cell lines. Complexes 2 and 5 demonstrated the highest activity. The plausible mechanisms of the antiproliferative activity of compounds, including the influence on the polymerization of Tb+MAP, are discussed. Some of the synthesized compounds have also actively induced apoptosis and blocked proliferation in the cell cycle G2/M phase.", "conclusion": "The plausible mechanisms of the antiproliferative activity of compounds, including the influence on the polymerization of Tb+MAP, are discussed. Some of the synthesized compounds have also actively induced apoptosis and blocked proliferation in the cell cycle G2/M phase." }, { "pmid": "36596238", "year": 2023, "title": "PdO-Nanoparticle-Embedded Carbon Nanotube Yarns for Wearable Hydrogen Gas Sensing Platforms with Fast and Sensitive Responses.", "title_en": null, "title_de": "PdO-Nanopartikel-eingebettete Kohlenstoffnanoröhren-Garne für tragbare Wasserstoffgas-Sensorplattformen mit schnellen und empfindlichen Reaktionen", "journal": "ACS sensors", "authors": "Son et al.", "author_search": "son son", "doi": "10.1021/acssensors.2c01743", "doi_url": "https://doi.org/10.1021/acssensors.2c01743", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36596238/", "url": "https://h2medicine.org/studies/study-son-2023-pdo-nanoparticle-embedded-carbon/", "methods": [ "inhalation" ], "indications": [ "sports-exercise", "joints-rheumatology", "fundamentals-safety" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2023 · Son — PdO-Nanoparticle-Embedded Carbon Nanotube Yarns for Wearable Hydrogen Gas Sensing Platforms with Fast and Sensitive Responses", "summary": "Researchers developed a flexible yarn-type sensor that detects explosive hydrogen concentrations within two seconds — opening a path toward wearable H₂ safety monitors. The sensor uses palladium oxide nanoparticles embedded in carbon nanotube yarn to sense H₂ with extraordinary sensitivity (1198%) and speed, even when bent around joints. This is a materials-science and safety study, not a biomedical therapy study.", "assessment": "This is a materials engineering study, not a clinical or therapeutic investigation. Its value lies entirely in the safety domain: it demonstrates that a flexible, body-conforming H₂ sensor with fast response and high sensitivity is technically feasible. No claims about H₂ health effects are made or should be inferred. For the H₂ medicine context, the work is relevant only as proof-of-concept for wearable leak monitoring — not as evidence of therapeutic benefit. The in-vitro character of the work means all results are lab-bench measurements; real-world wearable performance under sweat, body movement, and varying humidity has not yet been validated.", "abstract": "Hydrogen (H2) gas has recently become a crucial energy source and an imperative energy vector, emerging as a powerful next-generation solution for fuel cells and biomedical, transportation, and household applications. With increasing interest in H2, safety concerns regarding personal injuries from its flammability and explosion at high concentrations (>4%) have inspired the development of wearable pre-emptive gas monitoring platforms that can operate on curved and jointed parts of the human body. In this study, a yarn-type hydrogen gas sensing platform (HGSP) was developed by biscrolling of palladium oxide nanoparticles (PdO NPs) and spinnable carbon nanotube (CNT) buckypapers. Because of the high loading of H2-active PdO NPs (up to 97.7 wt %), when exposed to a flammable H2 concentration (4 vol %), the biscrolled HGSP yarn exhibits a short response time of 2 s, with a high sensitivity of 1198% (defined as ΔG/G0 × 100%). Interestingly, during the reduction of PdO to Pd by H2 gas, the HGSP yarn experienced a decrease in diameter and corresponding volume contraction. These excellent sensing performances suggest that the fabricated HGSP yarn could be applied to a wearable gas monitoring platform for real-time detection of H2 gas leakage even over the bends of joints.", "conclusion": "Interestingly, during the reduction of PdO to Pd by H2 gas, the HGSP yarn experienced a decrease in diameter and corresponding volume contraction. These excellent sensing performances suggest that the fabricated HGSP yarn could be applied to a wearable gas monitoring platform for real-time detection of H2 gas leakage even over the bends of joints." }, { "pmid": "36571379", "year": 2023, "title": "H2-induced transient upregulation of phospholipids with suppression of energy metabolism.", "title_en": null, "title_de": "H₂-induzierte vorübergehende Hochregulierung von Phospholipiden bei gleichzeitiger Unterdrückung des Energiestoffwechsels", "journal": "Medical gas research", "authors": "Iketani et al.", "author_search": "iketani iketani", "doi": "10.4103/2045-9912.344973", "doi_url": "https://doi.org/10.4103/2045-9912.344973", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36571379/", "url": "https://h2medicine.org/studies/study-iketani-2023-induced-transient-upregulation-phospholipids/", "methods": [ "inhalation" ], "indications": [ "metabolic", "sports-exercise", "neurology", "cardiovascular", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2023 · Iketani — H₂-induced transient upregulation of phospholipids with suppression of energy metabolism", "summary": "Short exposure to molecular hydrogen transiently shifts the lipid composition of neuroblastoma cells and temporarily suppresses their energy metabolism — a complex cellular response that hints at how H₂ may interact with cell membranes. This in-vitro cell study reveals that H₂ is not simply a passive antioxidant but actively changes lipid membranes and endosomal transport in human-derived neuroblastoma cells. Results cannot be directly transferred to living organisms.", "assessment": "This is an in-vitro mechanistic study on a single cancer-derived cell line. Its findings are scientifically interesting — they challenge the simple „H₂ as passive antioxidant” model and suggest a more nuanced stress-response mechanism. However, no therapeutic conclusions for humans can be drawn: the effects are transient, observed in neuroblastoma cells only, and the metabolic suppression and glutathione decrease would require careful interpretation in a living organism. The study is most valuable as a hypothesis-generator pointing to membrane lipid biology as a possible mechanism of H₂ action.", "abstract": "Molecular hydrogen (H2) is an antioxidant and anti-inflammatory agent; however, the molecular mechanisms underlying its biological effects are largely unknown. Similar to other gaseous molecules such as inhalation anesthetics, H2 is more soluble in lipids than in water. A recent study demonstrated that H2 reduces radical polymerization-induced cellular damage by suppressing fatty acid peroxidation and membrane permeability. Thus, we sought to examine the effects of short exposure to H2 on lipid composition and associated physiological changes in SH-SY5Y neuroblastoma cells. We analyzed cells by liquid chromatography-high-resolution mass spectrometry to define changes in lipid components. Lipid class analysis of cells exposed to H2 for 1 hour revealed transient increases in glycerophospholipids including phosphatidylethanolamine, phosphatidylinositol, and cardiolipin. Metabolomic analysis also showed that H2 exposure for 1 hour transiently suppressed overall energy metabolism accompanied by a decrease in glutathione. We further observed alterations to endosomal morphology by staining with specific antibodies. Endosomal transport of cholera toxin B to recycling endosomes localized around the Golgi body was delayed in H2-exposed cells. We speculate that H2-induced modification of lipid composition depresses energy production and endosomal transport concomitant with enhancement of oxidative stress, which transiently stimulates stress response pathways to protect cells.", "conclusion": "Endosomal transport of cholera toxin B to recycling endosomes localized around the Golgi body was delayed in H2-exposed cells. We speculate that H2-induced modification of lipid composition depresses energy production and endosomal transport concomitant with enhancement of oxidative stress, which transiently stimulates stress response pathways to protect cells." }, { "pmid": "36546774", "year": 2023, "title": "Two-Dimensional Mg2 Si Nanosheet-Enabled Sustained Hydrogen Generation for Improved Repair and Regeneration of Deeply Burned Skin.", "title_en": null, "title_de": "Zweidimensionale Mg₂Si-Nanoschichten ermöglichen eine anhaltende Wasserstofferzeugung zur verbesserten Reparatur und Regeneration tief verbrannter Haut", "journal": "Advanced healthcare materials", "authors": "Zhu et al.", "author_search": "zhu zhu", "doi": "10.1002/adhm.202201705", "doi_url": "https://doi.org/10.1002/adhm.202201705", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36546774/", "url": "https://h2medicine.org/studies/study-zhu-2023-two-dimensional-mg2-nanosheet/", "methods": [ "unspecified" ], "indications": [ "cancer", "skin-aging", "immune-system", "oxidative-stress", "fundamentals-safety" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2023 · Zhu — Two-Dimensional Mg₂Si Nanosheet-Enabled Sustained Hydrogen Generation for Improved Repair and Regeneration of Deeply Burned Skin", "summary": "A hydrogel dressing embedded with magnesium silicide nanosheets can continuously release molecular H₂ for about one week — and in animal and cell experiments, this sustained H₂ supply significantly accelerated healing of deep burn wounds without visible scarring. The mechanism involves anti-inflammatory macrophage reprogramming and scavenging of reactive oxygen species. This is an in-vitro and animal study; results cannot be directly extrapolated to humans.", "assessment": "This is a preclinical study combining in-vitro and animal experiments. It demonstrates a technically innovative, well-mechanistically-grounded H₂ delivery platform for burn wound care. The results in animal models are promising, and the mechanism (ROS scavenging, M2 polarization, CCL2/angiogenesis) is biologically coherent. No conclusions for human treatment can be drawn at this stage: no human trials have been conducted, clinical-grade safety data are absent, and the translation from animal burn models to human wounds involves substantial biological complexity. The study is best read as a strong preclinical proof-of-concept motivating further development.", "abstract": "Molecular hydrogen holds a high potential for wound healing owing to its anti-inflammatory effect and high biosafety, but commonly used hydrogen administration routes hardly achieve the sustained supply of high-dosage hydrogen, limiting hydrogen therapy efficacy. Here, two-dimensional Mg2 Si nanosheet (MSN) is exploited as a super-persistent hydrogen-releasing nanomaterial with high biocompatibility, and the incorporation of MSN into the chitosan/hyaluronic acid hydrogel (MSN@CS/HA) is developed as a dressing to repair deeply burned skin. The MSN@CS/HA hydrogel dressing can continuously generate hydrogen molecules for about 1 week in the physiological conditions in support of local, long-term, and plentiful hydrogen supply and remarkably promotes the healing and regeneration of deep second-degree and third-degree burn wounds without visible scar and toxic side effect. Mechanistically, a sustained supply of hydrogen molecules induces anti-inflammatory M2 macrophage polarization in time by enhancing CCL2 (chemokine C-C motif ligand 2) expression to promote angiogenesis and reduce fibrosis and also enhances the proliferation and migration capability of skin cells directly and indirectly by locally scavenging overexpressed reactive oxygen species, synergistically favoring wound repair. The proposed synthesis method, therapeutic strategy, and mechanisms will open a window for synthesizing a variety of MSene nanomaterials and developing their various proangiogenesis applications besides wound healing.", "conclusion": "Mechanistically, a sustained supply of hydrogen molecules induces anti-inflammatory M2 macrophage polarization in time by enhancing CCL2 (chemokine C-C motif ligand 2) expression to promote angiogenesis and reduce fibrosis and also enhances the proliferation and migration capability of skin cells directly and indirectly by locally scavenging overexpressed reactive oxygen species, synergistically f" }, { "pmid": "36529921", "year": 2023, "title": "Hydrogen-producing Photocatalyst at Sunscreen for Athletes in Preventing and Healing Muscle-nerve-skin Injuries.", "title_en": null, "title_de": "Wasserstoffproduzierender Photokatalysator in Sonnenschutzmitteln für Sportler zur Prävention und Heilung von Muskel-Nerven-Haut-Verletzungen", "journal": "Current topics in medicinal chemistry", "authors": "Sahoo", "author_search": "sahoo sahoo", "doi": "10.2174/1568026623666221216142158", "doi_url": "https://doi.org/10.2174/1568026623666221216142158", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36529921/", "url": "https://h2medicine.org/studies/study-sahoo-2023-producing-photocatalyst-sunscreen-athletes/", "methods": [ "bath-topical" ], "indications": [ "liver", "sports-exercise", "neurology", "cancer", "skin-aging" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2023 · Sahoo — Hydrogen-producing Photocatalyst at Sunscreen for Athletes in Preventing and Healing Muscle-nerve-skin Injuries", "summary": "A theoretical concept paper proposes embedding a UV-absorbing photocatalyst into a hydrogel sunscreen that would continuously split sweat into H₂ — allowing athletes to absorb H₂ through the skin during sun exposure. The idea is conceptually creative, but this is a purely theoretical in-vitro paper: no human or animal experiments have been performed, and no clinical efficacy data exist. Results cannot be transferred to any real-world application.", "assessment": "This is a purely theoretical concept paper — no experiments were performed, no animal or human data exist, and the therapeutic claims are speculative. Nothing here constitutes evidence of efficacy for any health condition. The photocatalytic H₂ production concept is interesting from an engineering standpoint, but the leap from the idea to actual transdermal H₂ delivery and clinical benefit is enormous and entirely unvalidated. Readers should treat this as a creative hypothesis paper, not as evidence that such a sunscreen product could or does provide any therapeutic effect.", "abstract": "Physical injuries in sports are unavoidable, but they can be mitigated and even treated by using molecular hydrogen, which can be administered via a specially formulated sunscreen. The photocatalysts are a special class of semiconductors that can absorb a specific spectrum of light to promote its electron from the valance band (VB) to the conduction band (CB). This creates positively charged holes at VB and negatively charged electrons at CB in generating photochemical reaction centres. Once a photocatalyst that absorbs a harmful UV band from sunlight and can split water is doped inside a hydrogel will produce hydrogen in the presence of sunlight. If we employ such photocatalyst-doped hydrogel over naked skin, the hydrogel will act as a continuous source of water, which will absorb water from sweet, store it inside the hydrogel matrix and deliver it to the photocatalyst for splitting it further into the hydrogen. As a result, such photocatalyst-doped hydrogel can be used as a sunscreen to protect against sunlight and can use that spectrum of light for producing hydrogen from sweat continuously. Hydrogen can be absorbed through the skin and diffused in the body to heal wound-prone or injured muscles, and nerves. Because hydrogen may travel throughout the body, the catalyst-doped hydrogel can be used as a topical gel to treat various ailments such as muscle-nerve skin injuries, cancer, Parkinson's disease, and others. Besides common people, even athletes can use it as sunscreen during sports, which is not feasible for other hydrogen administrating systems.", "conclusion": "Because hydrogen may travel throughout the body, the catalyst-doped hydrogel can be used as a topical gel to treat various ailments such as muscle-nerve skin injuries, cancer, Parkinson's disease, and others. Besides common people, even athletes can use it as sunscreen during sports, which is not feasible for other hydrogen administrating systems." }, { "pmid": "36516898", "year": 2023, "title": "Effects of molecular hydrogen intervention on the gut microbiome in methamphetamine abusers with mental disorder.", "title_en": null, "title_de": "Auswirkungen einer Intervention mit molekularem Wasserstoff auf das Darmmikrobiom bei Methamphetaminkonsumenten mit psychischer Störung.", "journal": "Brain research bulletin", "authors": "Wang et al.", "author_search": "wang wang", "doi": "10.1016/j.brainresbull.2022.12.003", "doi_url": "https://doi.org/10.1016/j.brainresbull.2022.12.003", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36516898/", "url": "https://h2medicine.org/studies/study-wang-2023-intervention-gut-microbiome-methamphetamine/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "sports-exercise", "neurology" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2023 · Wang — Effects of molecular hydrogen intervention on the gut microbiome in methamphetamine abusers with mental disorder.", "summary": "In female methamphetamine users suffering from depression and anxiety, both drinking and inhaling molecular hydrogen significantly alleviated mental health symptoms — and hydrogen inhalation also shifted gut microbiome composition. The finding connects gut bacteria, H₂ metabolism, and neuropsychiatric health in a vulnerable population. (Brain Research Bulletin, 2023.)", "assessment": "This is an interesting but preliminary study with significant limitations. Limitations: cohort is exclusively female METH users — a highly specific and non-generalizable population; no placebo or sham control for the H₂ intervention; the mechanism by which H₂ improves psychiatric scores is not established; no neuroimaging or biomarker endpoints; sample size appears small (not specified in abstract); the study cannot disentangle general behavioural effects of the intervention from H₂-specific effects. Nevertheless, the study is among the first to examine H₂ in a substance-abuse and mental-health context, and the microbiome-hydrogen-neuropsychiatry connection is a legitimate emerging hypothesis. Replication with controls in a larger sample is needed.", "abstract": "Methamphetamine (METH) is a potent and highly addictive psychostimulant and one of the most widely used illicit drugs, the abuse of which has become a severe public health problem worldwide. A growing amount of evidence has indicated potential connections between gut microbiota and mental disorders induced by METH and associations with neural and metabolic pathways. The present study aimed to explore the relationship between fecal microbial alterations and neuropsychiatric diseases in METH addictions. Thus, mental disorders and gut microbial alterations were analyzed by self-rating depression (SDS) and anxiety (SAS) scales and 16 S rRNA gene sequencing, respectively. Our results showed that increased SDS and SAS indices and decreased alpha diversity indicated more serious mental disorders and lower bacterial diversity in METH users than in the age-matched healthy control group. The gut microbial composition in female METH users was also significantly altered, with reductions in hydrogen-producing bacteria, including Bacteroides and Roseburia. Molecular hydrogen (H2) is spontaneously produced by intestinal bacteria in the process of anaerobic metabolism, which is the main pathway for H2 production in vivo. Numerous studies have shown that hydrogen intervention can significantly improve neuropsychiatric diseases, including Alzheimer's disease and Parkinson's disease. Our results showed that hydrogen intervention, including drinking and inhaling, significantly alleviated mental disorders induced by METH abuse, and the inhalation of hydrogen also altered gut microbiota profiles in the METH abusers. These results suggest that hydrogen intervention has potential therapeutic applicability in the treatment of mental disorders in METH abusers.", "conclusion": "Our results showed that hydrogen intervention, including drinking and inhaling, significantly alleviated mental disorders induced by METH abuse, and the inhalation of hydrogen also altered gut microbiota profiles in the METH abusers. These results suggest that hydrogen intervention has potential therapeutic applicability in the treatment of mental disorders in METH abusers." }, { "pmid": "36460289", "year": 2023, "title": "Long-term in vivo observations show biocompatibility and performance of ZX00 magnesium screws surface-modified by plasma-electrolytic oxidation in Göttingen miniature pigs.", "title_en": null, "title_de": "Langzeit-In-vivo-Beobachtungen zeigen Biokompatibilität und Leistung von ZX00-Magnesiumschrauben, deren Oberfläche durch plasmaelektrolytische Oxidation modifiziert wurde, bei Göttinger Miniaturschweinen", "journal": "Acta biomaterialia", "authors": "Kopp et al.", "author_search": "kopp kopp", "doi": "10.1016/j.actbio.2022.11.052", "doi_url": "https://doi.org/10.1016/j.actbio.2022.11.052", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36460289/", "url": "https://h2medicine.org/studies/study-kopp-2023-long-term-vivo-observations/", "methods": [ "inhalation" ], "indications": [ "sports-exercise" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2023 · Kopp — Long-term in vivo observations show biocompatibility and performance of ZX00 magnesium screws surface-modified by plasma-electrolytic oxidation in Göttingen miniature pigs", "summary": "Bioabsorbable magnesium bone screws with a special surface coating (plasma-electrolytic oxidation) showed good biocompatibility and significantly slower, more controlled degradation over 18 months in large animals — with H₂ evolution serving as a standard measurement tool during in-vitro degradation testing, not as a therapy. This is a preclinical orthopedic implant study in Göttingen miniature pigs; it tests implant materials, not H₂ as a therapeutic agent.", "assessment": "This study is not an H₂ therapy study — it is an orthopedic biomaterials study in which H₂ gas measurement is a laboratory tool. The finding that PEO surface modification improves degradation control and bone integration is clinically relevant for orthopedic surgery, and the 18-month large-animal dataset fills an important evidence gap for bioabsorbable magnesium implants. No conclusions about H₂ health benefits can be drawn from this paper. Its inclusion in an H₂ medicine context is relevant only for understanding that magnesium-based implants produce H₂ as a degradation byproduct — and that controlling this is important for implant safety.", "abstract": "Bioabsorbable magnesium implants for orthopedic fixation of bone have recently become available for different fields of indication. While general questions of biocompatibility have been answered, tailoring suitable degradation kinetics for specific applications as well as long-term tissue integration remain the focus of current research. The aim of this study was the evaluation of the long-term degradation behavior and osseointegration of Mg-Ca-Zn (ZX00MEO) based magnesium implants with plasma-electrolytic oxidation (PEO) surface modification (ZX00MEO-PEO) in comparison to non-surface modified implants in vivo and in vitro. Besides a general evaluation of the biological performance of the alloy over a prolonged period, the main hypothesis was that PEO surface modification significantly reduces implant degradation rate and improves tissue interaction. In vitro, the microstructure and surface of the bioabsorbable screws were characterized by SEM/EDS, cytocompatibility and degradation testing facilitating hydrogen gas evolution, carried out following ISO 10993-5/-12 and ASTM F3268-18a/ASTM G1-03 (E1:2017). In vivo, screws were implanted in the frontal bone of Minipigs for 6, 12, and 18 months, following radiological and histomorphometric analysis. A slower and more uniform degradation and improved cytocompatibility could be shown for the ZX00MEO-PEO group in vitro. A significant reduction of degradation rate and enhanced bone formation around the ZX00MEO-PEO screws in vivo was confirmed. Proficient biocompatibility and tissue integration could generally be shown in vivo regardless of surface state. The tested magnesium alloy shows generally beneficial properties as an implant material, while PEO-surface modification further improves the bioabsorption behavior both in vitro and in vivo. STATEMENT OF SIGNIFICANCE: Devices from bioabsorbable Magnesium have recently been introduced to orthopedic applications. However, the vast degradation of Magnesium within the human body still gives limitations. While reliable in-vivo data on most promising surface treatments such as Plasma-electrolytic-Oxidation is generally scarce, long-time results in large animals are to this date completely missing. To overcome this lack of evidence, we studied a Magnesium-Calzium-Zinc-alloy with surface enhancement by PEO for the first time ever over a period of 18 months in a large animal model. In-vitro, surface-modified screws showed significantly improved cytocompatibility and reduction of degradation confirmed by hydrogen gas evolution testing, while in-vivo radiological and histological evaluation generally showed good biocompatibility and bioabsorption as well as significantly enhanced reduction of degradation and faster bone regeneration in the PEO-surface-modified group.", "conclusion": "To overcome this lack of evidence, we studied a Magnesium-Calzium-Zinc-alloy with surface enhancement by PEO for the first time ever over a period of 18 months in a large animal model. In-vitro, surface-modified screws showed significantly improved cytocompatibility and reduction of degradation confirmed by hydrogen gas evolution testing, while in-vivo radiological and histological evaluation gene" }, { "pmid": "36330842", "year": 2023, "title": "Hydrogen suppresses oxidative stress by inhibiting the p38 MAPK signaling pathway in preeclampsia.", "title_en": null, "title_de": "Wasserstoff unterdrückt oxidativen Stress durch Hemmung des p38-MAPK-Signalwegs bei Präeklampsie", "journal": "Advances in clinical and experimental medicine : official organ Wroclaw Medical University", "authors": "Guo et al.", "author_search": "guo guo", "doi": "10.17219/acem/154623", "doi_url": "https://doi.org/10.17219/acem/154623", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36330842/", "url": "https://h2medicine.org/studies/study-guo-2023-suppresses-oxidative-stress-inhibiting/", "methods": [ "saline-iv" ], "indications": [ "cardiovascular", "cancer", "kidney-dialysis", "pregnancy", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2023 · Guo — Hydrogen suppresses oxidative stress by inhibiting the p38 MAPK signaling pathway in preeclampsia", "summary": "In a rat model of preeclampsia, hydrogen-rich saline significantly reduced inflammation markers, oxidative stress, and blood pressure-related damage — and the protective effect appears to work via inhibiting the p38 MAPK signaling pathway. This is an animal study in pregnant rats; the findings are mechanistically informative but cannot be directly applied to pregnant humans.", "assessment": "This is an animal study (rat preeclampsia model) — its findings are mechanistically valuable but do not constitute evidence that hydrogen-rich saline is safe or effective in pregnant humans. The L-NAME rat model is a useful research tool but does not fully replicate human preeclampsia. The p38 MAPK mechanism identified is biologically plausible and consistent with H₂'s known anti-inflammatory properties. Any consideration of HRS in human pregnancy would require rigorous clinical safety evaluation — pregnant women are a highly protected population and the absence of human data here is a major limitation.", "abstract": "BACKGROUND: Hypertensive disorders complicating pregnancy (HDCP) are one of the most serious medical disorders during pregnancy. OBJECTIVES: To investigate the effects of hydrogen on the mitogen-activated protein kinase (MAPK) signaling pathway in preeclampsia (PE). MATERIAL AND METHODS: The N(omega)-nitro-L-arginine methyl ester (L-NAME)-induced PE model with Sprague Dawley (SD) rats was employed. An inhibitor of MAPK signaling pathways (SB203580) was used as a p38 MAPK inhibitor. The SD rats were randomized into 5 groups: non-pregnant (NP); normal pregnancy (P); pregnancy + L-NAME (L); pregnancy + L-NAME + hydrogen-rich saline (LH); and pregnancy + L-NAME + hydrogen-rich saline + SB203580 (LHS). The pregnancies were terminated on day 22 of gestation, and the placentas and kidneys were microscopically inspected. Tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β) and malondialdehyde (MDA) levels were assessed. The mean systolic blood pressure (SBP) and level of proteinuria were recorded. The p38 MAPK mRNA expression and p-p38 MAPK protein levels were measured using real-time polymerase chain reaction (RT-PCR) and western blot, respectively. RESULTS: It was found that hydrogen-rich saline (LH group) decreased placental MDA, proteinuria, TNF-α, and IL-1β levels in the placental tissues compared with the L group (all p < 0.05). Additionally, hydrogen-rich saline (LH group) treatment significantly decreased the p38 MAPK mRNA expression and p-p38 MAPK protein levels compared with the L group (p < 0.05). The p38 MAPK inhibitor SB203580 (LHS group) further decreased the p38 MAPK mRNA expression and p-p38 MAPK protein levels compared with the LH group (p < 0.05). CONCLUSIONS: Hydrogen can decrease the reactive oxygen species (ROS) content and inhibit the MAPK pathway. The protective effect of hydrogen may be associated with the inhibition of the p38 MAPK signaling pathway.", "conclusion": "Hydrogen can decrease the reactive oxygen species (ROS) content and inhibit the MAPK pathway. The protective effect of hydrogen may be associated with the inhibition of the p38 MAPK signaling pathway." }, { "pmid": "36307299", "year": 2023, "title": "A potential clinical application of hydrogen-rich saline in postoperative care.", "title_en": null, "title_de": "Eine potenzielle klinische Anwendung von wasserstoffreicher Kochsalzlösung in der postoperativen Versorgung", "journal": "Journal of pediatric surgery", "authors": "Wong et al.", "author_search": "wong wong", "doi": "10.1016/j.jpedsurg.2022.09.041", "doi_url": "https://doi.org/10.1016/j.jpedsurg.2022.09.041", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36307299/", "url": "https://h2medicine.org/studies/study-wong-2023-application-saline-postoperative-care/", "methods": [ "saline-iv" ], "indications": [ "other" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2023 · Wong — A potential clinical application of hydrogen-rich saline in postoperative care", "summary": "This review article discusses potential clinical uses of hydrogen-rich saline in postoperative care, but no abstract text is publicly available for this record. According to the DOI (10.1016/j.jpedsurg.2022.09.041), this is a paper in the Journal of Pediatric Surgery. A full assessment would require access to the complete article via the journal or library access.", "assessment": "No abstract is available for this record. We cannot evaluate the content, quality, or conclusions of this review without the full text. As a review article, it would represent a synthesis of existing studies, not new experimental evidence. Readers interested in this paper should consult the original publication via the DOI. No therapeutic claims can be made or assessed based on the available information.", "abstract": null, "conclusion": null }, { "pmid": "36165523", "year": 2023, "title": "Molecular Hydrogen Promotes Adipose-derived Stem Cell Myogenic Differentiation via Regulation of Mitochondria.", "title_en": null, "title_de": "Molekularer Wasserstoff fördert die myogene Differenzierung von aus Fettgewebe stammenden Stammzellen über die Regulation der Mitochondrien", "journal": "Current stem cell research & therapy", "authors": "Yang et al.", "author_search": "yang yang", "doi": "10.2174/1574888x17666220926115240", "doi_url": "https://doi.org/10.2174/1574888x17666220926115240", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36165523/", "url": "https://h2medicine.org/studies/study-yang-2023-promotes-adipose-derived-stem/", "methods": [ "unspecified" ], "indications": [ "metabolic", "sports-exercise", "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2023 · Yang — Molecular Hydrogen Promotes Adipose-derived Stem Cell Myogenic Differentiation via Regulation of Mitochondria", "summary": "In cell culture experiments, exposing fat-tissue-derived stem cells to molecular hydrogen significantly improved their survival and their ability to differentiate into muscle cells — an effect linked to improved mitochondrial function and reduced oxidative stress. This is an in-vitro study only; whether H₂ could improve stem cell therapy outcomes in living organisms or humans remains to be investigated.", "assessment": "This is an in-vitro cell study using a human-derived stem cell line. Its findings — that H₂ improves mitochondrial function, reduces ROS, and enhances ADSC myogenic differentiation — are scientifically interesting and mechanistically plausible. However, no animal or human data exist for this specific approach, and no conclusions about clinical benefit can be drawn. The study contributes to the basic science foundation of potential H₂-assisted stem cell therapy for muscle disease, but considerable preclinical and clinical development would be needed before any therapeutic application.", "abstract": "BACKGROUND: Acute skeletal muscle injuries are common physical or sports traumas. Cellular therapy has excellent potential for regeneration after skeletal muscle injury. Adipose-derived stem cells (ADSCs) are a more accessible type of stem cell. However, it has a low survival rate and differentiation efficiency in the oxidative stress-rich microenvironment after transplantation. Although molecular hydrogen (H2) possesses anti-inflammatory and antioxidant biological properties, its utility in mitochondrial and stem cell research has not been adequately explored. OBJECTIVE: This study aimed to reveal the role of H2 on adipose-derived stem cells' myogenic differentiation. METHODS: The protective effects of H2 in ADSCs were evaluated by MTT assay, live-dead cell staining, western blot analysis, immunofluorescence staining, confocal imaging, and transmission electron microscopy. RESULTS: An appropriate volume fraction of H2 significantly decreased mitochondrial reactive oxygen species (ROS) levels, increased the number of mitochondria, and promoted mitophagy, thus enhancing the survival and myogenic differentiation of ADSCs. CONCLUSION: This study reveals the application potential of H2 in skeletal muscle diseases or other pathologies related to mitochondrial dysfunction.", "conclusion": "This study reveals the application potential of H2 in skeletal muscle diseases or other pathologies related to mitochondrial dysfunction." }, { "pmid": "35962590", "year": 2023, "title": "Hydrogen Gas Inhalation Attenuates Acute Impulse Noise Trauma: A Preclinical In Vivo Study.", "title_en": null, "title_de": "Die Inhalation von Wasserstoffgas schwächt akute Impulslärm-Traumata ab: Eine präklinische In-vivo-Studie", "journal": "The Annals of otology, rhinology, and laryngology", "authors": "Videhult Pierre et al.", "author_search": "videhult pierre videhult pierre", "doi": "10.1177/00034894221118764", "doi_url": "https://doi.org/10.1177/00034894221118764", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/35962590/", "url": "https://h2medicine.org/studies/study-videhultpierre-2023-inhalation-attenuates-acute-impulse/", "methods": [ "inhalation" ], "indications": [ "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2023 · Videhult Pierre — Hydrogen Gas Inhalation Attenuates Acute Impulse Noise Trauma: A Preclinical In Vivo Study", "summary": "In guinea pigs subjected to extremely loud impulse noise (156 dB), inhaling 2% H₂ immediately afterwards significantly reduced hearing threshold shifts and inner ear hair cell loss compared to noise-only controls. This animal study suggests H₂ inhalation may protect against acute acoustic trauma by reducing oxidative stress in the cochlea — but results cannot be directly applied to humans.", "assessment": "This is a preclinical animal study (guinea pigs). The results are consistently positive and the study design is rigorous for an animal model, with appropriate controls and multi-frequency ABR measurements. These findings cannot be directly applied to human acoustic trauma prevention or treatment. The guinea pig cochlea responds similarly to humans in some respects but not all. Human studies with H₂ inhalation for noise-induced hearing loss are currently absent. The 4-day follow-up is short for assessing long-term hearing recovery. This study provides a solid preclinical rationale for further investigation, including human trials.", "abstract": "OBJECTIVE: Molecular hydrogen (H2) has shown therapeutic potential in several oxidative stress-related conditions in humans, is well-tolerated, and is easily administered via inhalation.The aim of this preclinical in vivo study was to investigate whether impulse noise trauma can be prevented by H2 when inhaled immediately after impulse noise exposure. METHODS: Guinea pigs (n = 26) were subjected to impulse noise (n = 400; 156 dB SPL; 0.33/s; n = 11; the Noise group), to impulse noise immediately followed by H2 inhalation (2 mol%; 500 ml/min; 1 hour; n = 10; the Noise + H2 group), or to H2 inhalation (n = 5; the H2 group). The acoustically evoked ABR threshold at 3.15, 6.30, 12.5, 20.0, and 30.0 kHz was assessed before and 4 days after impulse noise and/or H2 exposure. The cochleae were harvested after the final ABR assessment for quantification of hair cells. RESULTS: Noise exposure caused ABR threshold elevations at all frequencies (median 35, 35, 30, 35, and 35 dB SPL, the Noise group; 20, 25, 10, 13, and 20 dB SPL, the Noise + H2 group; P < .05) but significantly less so in the Noise + H2 group (P < .05). Outer hair cell (OHC) loss was in the apical, mid, and basal regions 8.8%, 53%, and 14% in the Noise group and 3.5%, 22%, and 1.2% in the Noise + H2 group. The corresponding inner hair cell (IHC) loss was 0.1%, 14%, and 3.5% in the Noise group and 0%, 2.8%, and 0% in the Noise + H2 group. The difference between the groups was significant in the basal region for OHCs (P = .003) and apical (P = .033) and basal (P = .048) regions for IHCs. CONCLUSIONS: Acute acoustic trauma can be reduced by H2 when inhaled immediately after impulse noise exposure.", "conclusion": "Acute acoustic trauma can be reduced by H2 when inhaled immediately after impulse noise exposure." }, { "pmid": "36499079", "year": 2022, "title": "Electrolyzed-Reduced Water: Review I. Molecular Hydrogen Is the Exclusive Agent Responsible for the Therapeutic Effects", "title_en": null, "title_de": "Elektrolytisch reduziertes Wasser, Review I: Molekularer Wasserstoff ist der alleinige Wirkstoff für die therapeutischen Effekte", "journal": "International Journal of Molecular Sciences", "authors": "LeBaron et al.", "author_search": "lebaron le baron", "doi": "10.3390/ijms232314750", "doi_url": "https://doi.org/10.3390/ijms232314750", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36499079/", "url": "https://h2medicine.org/studies/study-lebaron-2022-electrolyzed-reduced-water-exclusive-agent/", "methods": [ "drinking-hrw" ], "indications": [ "fundamentals", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2022 · LeBaron — Electrolyzed-Reduced Water: Review I. Molecular Hydrogen Is the Exclusive Agent Responsible for the Therapeutic Effects", "summary": "With alkaline electrolyzed-reduced water (ERW), it is not „alkaline water“, not „microclusters“, not „free electrons“ that work — but solely the dissolved molecular hydrogen (H₂). This review clears away the pseudo-scientific marketing and traces every documented effect back to H₂. (International Journal of Molecular Sciences, 2022.)", "assessment": "This is a key reference for the field. It provides the honest, engineering-clean argument that separates serious H₂ use from the esoteric „miracle-machine“ narrative: it is not about „magic alkaline water“ but about a measurable H₂ dose. Mechanistically it puts H₂ concentration at the centre — instead of pH or ORP showmanship. The paper comes from a recognised specialist author (LeBaron, Molecular Hydrogen Institute) and is a systematic synthesis of the primary literature. Limitations, stated honestly: it is a review, not new proof of efficacy — and LeBaron is not impartial in the H₂ field (conflict-of-interest context through his role at the Molecular Hydrogen Institute). Its strength is the mechanistic-chemical debunking of myths, not new clinical endpoints.", "abstract": "Numerous benefits have been attributed to alkaline-electrolyzed-reduced water (ERW). Sometimes these claims are associated with easily debunked concepts. The observed benefits have been conjectured to be due to the intrinsic properties of ERW (e.g., negative oxidation-reduction potential (ORP), alkaline pH, H2 gas), as well enigmatic characteristics (e.g., altered water structure, microclusters, free electrons, active hydrogen, mineral hydrides). The associated pseudoscientific marketing has contributed to the reluctance of mainstream science to accept ERW as having biological effects. Finally, through many in vitro and in vivo studies, each one of these propositions was examined and refuted one-by-one until it was conclusively demonstrated that H2 was the exclusive agent responsible for both the negative ORP and the observed therapeutic effects of ERW. This article briefly apprised the history of ERW and comprehensively reviewed the sequential research demonstrating the importance of H2. We illustrated that the effects of ERW could be readily explained by the known biological effects of H2 and by utilizing conventional chemistry without requiring any metaphysical conjecture (e.g., microclustering, free electrons, etc.) or reliance on implausible notions (e.g., alkaline water neutralizes acidic waste). The H2 concentration of ERW should be measured to ensure it is comparable to those used in clinical studies.", "conclusion": "We illustrated that the effects of ERW could be readily explained by the known biological effects of H2 and by utilizing conventional chemistry without requiring any metaphysical conjecture (e.g., microclustering, free electrons, etc.) or reliance on implausible notions (e.g., alkaline water neutralizes acidic waste). The H2 concentration of ERW should be measured to ensure it is comparable to tho" }, { "pmid": "35920994", "year": 2022, "title": "Impact of nutraceuticals and dietary supplements on mitochondria modifications in healthy aging: a systematic review of randomized controlled trials.", "title_en": null, "title_de": "Auswirkungen von Nutrazeutika und Nahrungsergänzungsmitteln auf mitochondriale Veränderungen beim gesunden Altern: Eine systematische Übersichtsarbeit randomisierter kontrollierter Studien", "journal": "Aging clinical and experimental research", "authors": "Lippi et al.", "author_search": "lippi lippi", "doi": "10.1007/s40520-022-02203-y", "doi_url": "https://doi.org/10.1007/s40520-022-02203-y", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/35920994/", "url": "https://h2medicine.org/studies/study-lippi-2022-impact-nutraceuticals-dietary-supplements/", "methods": [ "drinking-hrw" ], "indications": [ "skin-aging", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2022 · Lippi — Impact of nutraceuticals and dietary supplements on mitochondria modifications in healthy aging: a systematic review of randomized controlled trials", "summary": "This systematic review of 6 randomized controlled trials found that dietary supplements — including hydrogen-rich water — show positive effects on mitochondrial function markers in healthy older adults, but the total evidence base is small and further research is needed. As a review article, it synthesizes existing studies rather than generating new data; H₂ is one of six supplements evaluated, not the sole focus.", "assessment": "This is a systematic review of RCTs — methodologically a high-quality study type (evidence level 4 as a review). However, with only 6 included trials covering 201 participants and 6 different supplements, the evidence base for any individual supplement (including H₂-rich water) is extremely thin. The review cannot be used to make strong therapeutic claims about hydrogen-rich water specifically, as H₂ is just one of multiple supplements examined and individual study results are not disaggregated in full detail for H₂ alone. The honest takeaway: there are early positive signals for several mitochondria-targeting supplements in healthy aging, but the field is in its infancy and requires much larger, longer-term trials.", "abstract": "BACKGROUND: To date, the mitochondrial function has been related to several pathways involved in the cellular aging process. Dietary supplements might have reciprocal and multilevel interactions with mitochondria network; however, no systematic review assessed the role of different nutraceuticals in mitochondria modification of healthy older adults. AIM: To assess the effects of different dietary supplements on mitochondria modifications in older adults. METHODS: On February 22, 2022, PubMed, Scopus, Web of Science, and Cochrane were systematically searched from inception for randomized controlled trials (RCTs). According to PICO model, we considered healthy older adults as participants, nutraceutical treatment as intervention, any treatment as comparator, mitochondrial modifications as outcome. Jadad scale was used for the quality assessment. RESULTS: Altogether, 8489 records were identified and screened until 6 studies were included. A total of 201 healthy older adults were included in the systematic review (mean age ranged from 67.0 ± 1.0 years to 76.0 ± 5.6 years). The dietary supplements assessed were sodium nitrite, N-3 polyunsaturated fatty acids, hydrogen-rich water, nicotinamide riboside, urolithin A, and whey protein powder. Positive effects were reported in terms of mitochondrial oxidative and antioxidant capacity, volume, bioenergetic capacity, and mitochondrial transcriptome based on the nutritional supplements. The quality assessment underlined that all the studies included were of good quality. DISCUSSION: Although dietary supplements might provide positive effects on mitochondria modifications, few studies are currently available in this field. CONCLUSION: Further studies are needed to better elucidate the reciprocal and multilevel interactions between nutraceuticals, mitochondria, and environmental stressors in healthy older adults.", "conclusion": "Further studies are needed to better elucidate the reciprocal and multilevel interactions between nutraceuticals, mitochondria, and environmental stressors in healthy older adults." }, { "pmid": "35489460", "year": 2022, "title": "Electrocoagulation and electrooxidation technologies for pesticide removal from water or wastewater: A review.", "title_en": null, "title_de": "Elektrokoagulations- und Elektrooxidationstechnologien zur Entfernung von Pestiziden aus Wasser oder Abwasser: Eine Übersichtsarbeit", "journal": "Chemosphere", "authors": "Biswas et al.", "author_search": "biswas biswas", "doi": "10.1016/j.chemosphere.2022.134709", "doi_url": "https://doi.org/10.1016/j.chemosphere.2022.134709", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/35489460/", "url": "https://h2medicine.org/studies/study-biswas-2022-electrocoagulation-electrooxidation-technologies-pesticide/", "methods": [ "inhalation" ], "indications": [ "neurology", "cancer", "respiratory" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2022 · Biswas — Electrocoagulation and electrooxidation technologies for pesticide removal from water or wastewater: A review", "summary": "This review covers electrochemical methods — electrocoagulation and electrooxidation — for removing pesticides from water, and notes that H₂ gas is generated as a byproduct at the cathode during electrocoagulation. This is an environmental engineering review with no connection to H₂ medicine, therapy, or health effects of molecular hydrogen. H₂ appears solely as a technical process byproduct.", "assessment": "This review is not relevant to H₂ medicine or therapy. It is a water-treatment engineering paper in which H₂ appears solely as an incidental byproduct of the electrocoagulation process. No health, therapeutic, or biomedical conclusions can be drawn from this paper. Its inclusion in an H₂ research database is a categorization artifact. Readers seeking evidence about health effects of molecular hydrogen should consult dedicated H₂ medicine literature.", "abstract": "Pesticides are known to be threats to the environment and human health. Excessive use of pesticides in agricultural practice can contaminate water bodies, leading to cancer, asthma, neurological disorders, reproductive defects, and hormonal disruption. Electrochemical methods such as electrocoagulation and electrooxidation can be used for pesticide removal due to their numerous advantages such as high efficiency, less sludge production, and low operational cost. During electrocoagulation, dissolution of anode metals results in metal hydroxide complexes, which precipitate with the contaminant present in the reactor. Simultaneously, electro-flotation occurs at the cathode and results in the evolution of hydrogen gas bubbles, leading to flotation of floc to the top surface of the reactor. This review focuses on the removal mechanisms, kinetics, modeling, effects of influencing factors, and sludge characterization of pesticide removal using electrocoagulation and electrooxidation. Major influencing factors include cell configuration, electrode material, current density, pH, supporting electrolyte concentration. In general, aluminum and iron are the most common electrodes used for pesticide removal using electrocoagulation, while boron-doped diamond was used to a far greater extent as the electrode in electrooxidation studies. Greater than 99% removal efficiency was observed in both processes. Overall, this review summarizes the use of electrochemical methods for pesticide removal and offers valuable information to researchers in this area of study.", "conclusion": "Greater than 99% removal efficiency was observed in both processes. Overall, this review summarizes the use of electrochemical methods for pesticide removal and offers valuable information to researchers in this area of study." }, { "pmid": "35340218", "year": 2022, "title": "Role of Molecular Hydrogen in Ageing and Ageing-Related Diseases.", "title_en": null, "title_de": "Die Rolle von molekularem Wasserstoff beim Altern und alternsbedingten Erkrankungen", "journal": "Oxidative medicine and cellular longevity", "authors": "Fu et al.", "author_search": "fu fu", "doi": "10.1155/2022/2249749", "doi_url": "https://doi.org/10.1155/2022/2249749", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/35340218/", "url": "https://h2medicine.org/studies/study-fu-2022-ageing-ageing-related-diseases/", "methods": [ "unspecified" ], "indications": [ "diabetes", "neurology", "cardiovascular", "cancer", "respiratory", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2022 · Fu — Role of Molecular Hydrogen in Ageing and Ageing-Related Diseases", "summary": "This comprehensive review summarizes how molecular hydrogen may counteract multiple hallmarks of biological aging — from oxidative stress and genomic instability to mitochondrial dysfunction and chronic inflammation — and surveys its potential role in age-related diseases such as neurodegeneration, cardiovascular disease, diabetes, and cancer. As a review article, it synthesizes existing preclinical and clinical research rather than providing new experimental data; conclusions are theoretical and evidence quality varies substantially by topic.", "assessment": "This is a narrative review covering a wide field with heterogeneous underlying evidence. The breadth is both its strength and its weakness: covering aging hallmarks, specific organ systems, and multiple diseases necessarily means that evidence quality varies enormously — from well-controlled human trials (for some conditions) to purely theoretical mechanistic arguments or single animal studies (for others). This review cannot be cited as blanket clinical proof for H₂ in aging or any specific disease. It is most appropriately used as a map of the H₂-aging research landscape and a source of mechanistic hypotheses for future investigation. Readers should consult primary studies for each specific disease area mentioned.", "abstract": "Ageing is a physiological process of progressive decline in the organism function over time. It affects every organ in the body and is a significant risk for chronic diseases. Molecular hydrogen has therapeutic and preventive effects on various organs. It has antioxidative properties as it directly neutralizes hydroxyl radicals and reduces peroxynitrite level. It also activates Nrf2 and HO-1, which regulate many antioxidant enzymes and proteasomes. Through its antioxidative effect, hydrogen maintains genomic stability, mitigates cellular senescence, and takes part in histone modification, telomere maintenance, and proteostasis. In addition, hydrogen may prevent inflammation and regulate the nutrient-sensing mTOR system, autophagy, apoptosis, and mitochondria, which are all factors related to ageing. Hydrogen can also be used for prevention and treatment of various ageing-related diseases, such as neurodegenerative disorders, cardiovascular disease, pulmonary disease, diabetes, and cancer. This paper reviews the basic research and recent application of hydrogen in order to support hydrogen use in medicine for ageing prevention and ageing-related disease therapy.", "conclusion": "Hydrogen can also be used for prevention and treatment of various ageing-related diseases, such as neurodegenerative disorders, cardiovascular disease, pulmonary disease, diabetes, and cancer. This paper reviews the basic research and recent application of hydrogen in order to support hydrogen use in medicine for ageing prevention and ageing-related disease therapy." }, { "pmid": "35240982", "year": 2022, "title": "Molecular hydrogen is a potential protective agent in the management of acute lung injury.", "title_en": null, "title_de": "Molekularer Wasserstoff ist ein potenzielles Schutzmittel im Management der akuten Lungenschädigung", "journal": "Molecular medicine (Cambridge, Mass.)", "authors": "Zhang et al.", "author_search": "zhang zhang", "doi": "10.1186/s10020-022-00455-y", "doi_url": "https://doi.org/10.1186/s10020-022-00455-y", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/35240982/", "url": "https://h2medicine.org/studies/study-zhang-2022-protective-agent-management-acute/", "methods": [ "unspecified" ], "indications": [ "respiratory", "immune-system" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2022 · Zhang et al. — Molecular Hydrogen Is a Potential Protective Agent in the Management of Acute Lung Injury", "summary": "Molecular hydrogen (H₂) may offer protective effects in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) — two life-threatening conditions seen in critically ill patients, including those with severe COVID-19. This review summarises the key biological mechanisms by which H₂ may counteract the underlying pathology of ALI, including anti-inflammation, antioxidation, and regulation of cell death. (Molecular Medicine, 2022.)", "assessment": "This is a review article — it synthesises existing preclinical and theoretical literature but presents no new experimental data. The mechanistic arguments for H₂ in lung injury are scientifically grounded and consistent with the broader H₂ biology literature. However, robust clinical evidence from randomised controlled trials in ALI/ARDS patients is still lacking. Honest limitation: the COVID-19 connection in particular is speculative, as the review does not present controlled human trial data for H₂ in COVID-19 patients. The paper is useful as a research roadmap but should not be read as clinical evidence of efficacy.", "abstract": "Acute lung injury (ALI) and acute respiratory distress syndrome, which is a more severe form of ALI, are life-threatening clinical syndromes observed in critically ill patients. Treatment methods to alleviate the pathogenesis of ALI have improved to a great extent at present. Although the efficacy of these therapies is limited, their relevance has increased remarkably with the ongoing pandemic caused by the novel coronavirus disease 2019 (COVID-19), which causes severe respiratory distress syndrome. Several studies have demonstrated the preventive and therapeutic effects of molecular hydrogen in the various diseases. The biological effects of molecular hydrogen mainly involve anti-inflammation, antioxidation, and autophagy and cell death modulation. This review focuses on the potential therapeutic effects of molecular hydrogen on ALI and its underlying mechanisms and aims to provide a theoretical basis for the clinical treatment of ALI and COVID-19.", "conclusion": "The biological effects of molecular hydrogen mainly involve anti-inflammation, antioxidation, and autophagy and cell death modulation. This review focuses on the potential therapeutic effects of molecular hydrogen on ALI and its underlying mechanisms and aims to provide a theoretical basis for the clinical treatment of ALI and COVID-19." }, { "pmid": "33555824", "year": 2022, "title": "Hydrogen Rich Water Consumption Positively Affects Muscle Performance, Lactate Response, and Alleviates Delayed Onset of Muscle Soreness After Resistance Training", "title_en": null, "title_de": "Der Konsum von wasserstoffreichem Wasser wirkt sich positiv auf Muskelleistung und Laktatantwort aus und lindert den verzögert auftretenden Muskelkater nach Krafttraining", "journal": "Journal of Strength and Conditioning Research", "authors": "Botek et al.", "author_search": "botek botek", "doi": "10.1519/jsc.0000000000003979", "doi_url": "https://doi.org/10.1519/jsc.0000000000003979", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33555824/", "url": "https://h2medicine.org/studies/study-botek-2022-muscle-performance-delayed-onset-soreness-resistance-training/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise", "oxidative-stress" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2022 · Botek — Hydrogen Rich Water Consumption Positively Affects Muscle Performance, Lactate Response, and Alleviates Delayed Onset of Muscle Soreness After Resistance Training", "summary": "Hydrogen-rich water improves muscle performance, lowers the lactate response and alleviates muscle soreness after resistance training. In a randomized double-blind crossover (12 men), muscle soreness after 24 hours was markedly lower (26 vs. 41 mm, p = 0.002). (J Strength Cond Res, 2022.)", "assessment": "Directly relevant to recovery from strength and fitness training, because the endpoint „delayed-onset muscle soreness“ (DOMS) is very tangible in everyday practice. The double-blind crossover design largely excludes placebo effects — each subject is their own control. Mechanistically, the lower lactate and soreness findings fit the antioxidant, inflammation-modulating profile of H₂. Limitation, stated honestly: very small sample (n = 12), only men, acute single dose — no statement about chronic intake or training adaptation over weeks.", "abstract": "Botek, M, Krejčí, J, McKune, A, Valenta, M, and Sládečková, B. Hydrogen rich water consumption positively affects muscle performance, lactate response, and alleviates delayed onset of muscle soreness after resistance training. J Strength Cond Res 36(10): 2792-2799, 2022-Positive outcomes of hydrogen rich water (HRW) supplementation on endurance performance have been shown, but the effects of HRW in resistance training are unclear. The aim of this study was to assess the effects of 1,260 ml of HRW intake on physiological, perceptual, and performance responses to a resistance training and after 24 hours of recovery. This randomized, double-blinded placebo-controlled cross-over study included 12 men aged 23.8 ± 1.9 years. Subjects performed a half squat, knee flexion, and extension exercises with the load set at 70% of 1 repetition maximum for 3 sets (10 reps/set). Lunges were performed with a load of 30% of body mass for 3 sets (20 reps/set). Time of each set, lactate, and ratings of perceived exertion were assessed mid-way through exercise and immediately after the exercise. Creatine kinase, muscle soreness visual analog scale ratings, countermovement jump, and heart rate variability were evaluated before the training and at 30 minutes, 6, and 24 hours of recovery. Lunges were performed faster with HRW compared with placebo ( p < 0.001). Hydrogen rich water reduced lactate at mid-way and immediately after the exercise (HRW: 5.3 ± 2.1 and 5.1 ± 2.2, placebo: 6.5 ± 1.8 and 6.3 ± 2.2 mmol·L -1 , p ≤ 0.008). Visual analog scale ratings were significantly lower with HRW (26 ± 11 vs. 41 ± 20 mm, p = 0.002) after 24 hours of recovery. In conclusion, an acute intermittent HRW hydration improved muscle function, reduced the lactate response, and alleviated delayed onset of muscle soreness.", "conclusion": "41 ± 20 mm, p = 0.002) after 24 hours of recovery. In conclusion, an acute intermittent HRW hydration improved muscle function, reduced the lactate response, and alleviated delayed onset of muscle soreness." }, { "pmid": "35206179", "year": 2022, "title": "Molecular Hydrogen Positively Affects Physical and Respiratory Function in Acute Post-COVID-19 Patients: A New Perspective in Rehabilitation", "title_en": null, "title_de": "Molekularer Wasserstoff beeinflusst die körperliche und respiratorische Funktion bei akuten Post-COVID-19-Patienten positiv: eine neue Perspektive in der Rehabilitation", "journal": "International Journal of Environmental Research and Public Health", "authors": "Botek et al.", "author_search": "botek botek", "doi": "10.3390/ijerph19041992", "doi_url": "https://doi.org/10.3390/ijerph19041992", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/35206179/", "url": "https://h2medicine.org/studies/study-botek-2022-post-covid-19-respiratory-rehabilitation/", "methods": [ "inhalation" ], "indications": [ "respiratory", "immune-system", "oxidative-stress", "sports-exercise" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2022 · Botek — Molecular Hydrogen Positively Affects Physical and Respiratory Function in Acute Post-COVID-19 Patients: A New Perspective in Rehabilitation", "summary": "Hydrogen inhalation improves lung and body function after COVID-19. In a randomized, placebo-controlled study of 50 acute post-COVID patients, 14 days of H₂ inhalation increased the 6-minute walking distance by 64 m and measurably improved vital capacity (all p ≤ 0.025). (IJERPH, 2022.)", "assessment": "Relevant for the H₂ inhalation segment and as an example of a modern, clinically tangible indication. The endpoints (6-minute walk test, spirometry) are established, objective measures — not a pure well-being self-report. It demonstrates that H₂ inhalation is being investigated in a medically relevant rehabilitation context. Limitation, stated honestly: only single-blind (expectation effects in the walk test not fully excluded), n = 50, short 14-day phase, no statement on long-term benefit or on long COVID. No conflict-of-interest information can be derived from the abstract.", "abstract": "Molecular hydrogen (H2) is potentially a novel therapeutic gas for acute post-coronavirus disease 2019 (COVID-19) patients because it has antioxidative, anti-inflammatory, anti-apoptosis, and antifatigue properties. The aim of this study was to determine the effect of 14 days of H2 inhalation on the respiratory and physical fitness status of acute post-COVID-19 patients. This randomized, single-blind, placebo-controlled study included 26 males (44 ± 17 years) and 24 females (38 ± 12 years), who performed a 6-min walking test (6 MWT) and pulmonary function test, specifically forced vital capacity (FVC) and expiratory volume in the first second (FEV1). Symptomatic participants were recruited between 21 and 33 days after a positive polymerase chain reaction test. The experiment consisted of H2/placebo inhalation, 2 × 60 min/day for 14 days. Results showed that H2 therapy, compared with placebo, significantly increased 6 MWT distance by 64 ± 39 m, FVC by 0.19 ± 0.24 L, and, in FEV1, by 0.11 ± 0.28 L (all p ≤ 0.025). In conclusion, H2 inhalation had beneficial health effects in terms of improved physical and respiratory function in acute post-COVID-19 patients. Therefore, H2 inhalation may represent a safe, effective approach for accelerating early function restoration in post-COVID-19 patients.", "conclusion": "In conclusion, H2 inhalation had beneficial health effects in terms of improved physical and respiratory function in acute post-COVID-19 patients. Therefore, H2 inhalation may represent a safe, effective approach for accelerating early function restoration in post-COVID-19 patients." }, { "pmid": "35276867", "year": 2022, "title": "Molecular Hydrogen Mitigates Performance Decrement during Repeated Sprints in Professional Soccer Players", "title_en": null, "title_de": "Molekularer Wasserstoff mildert den Leistungsabfall bei wiederholten Sprints bei Profi-Fußballern", "journal": "Nutrients", "authors": "Botek et al.", "author_search": "botek botek", "doi": "10.3390/nu14030508", "doi_url": "https://doi.org/10.3390/nu14030508", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/35276867/", "url": "https://h2medicine.org/studies/study-botek-2022-repeated-sprints-soccer-players/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise", "oxidative-stress" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2022 · Botek — Molecular Hydrogen Mitigates Performance Decrement during Repeated Sprints in Professional Soccer Players", "summary": "Hydrogen-rich water curbs performance decline during repeated sprints. In a randomized, double-blind crossover trial with 16 professional soccer players, the final sprints after H₂ water were measurably faster — up to 3.4 % faster over 15 m in the 14th and 15th sprints. (Nutrients, 2022.)", "assessment": "Directly relevant to repeated-sprint performance under fatigue: the crossover design (each athlete is their own control) and the double-blinding strongly reduce placebo and expectation effects — a frequent weakness in supplement studies. The finding fits mechanistically the antioxidant profile of H₂: less fatigue-related performance decline under high ROS load. Limitation, stated honestly: small sample (n = 16), only young male professionals, acute single dose before the test (no long-term effect studied). The fact that lactate and RPE remained unchanged leaves the precise mechanism open.", "abstract": "Hydrogen-rich water (HRW) supplementation has been shown to have an antifatigue effect across different modes of exercise. However, its effect on repeated sprint performance is unknown. The aim of this study was to assess the effect of pre-exercise HRW consumption on repeated sprint performance, lactate, and perceptual responses using a repeated sprint protocol. This randomized, double blinded, placebo controlled, crossover study included 16 professional, male soccer players aged 18.8 ± 1.2 years. Athletes performed two indoor tests, particularly 15 × 30 m track sprints interspersed by 20 s of recovery, separated by a 1-week washout period. Sprint time was measured at 15 m and 30 m. Ratings of perceived exertion were assessed immediately after each sprint, and post-exercise blood lactate concentration was measured after the last sprint. There were significantly faster sprint times after HRW consumption compared with placebo at 15 m for the 14th and 15th sprints, representing improvements in time of 3.4% and 2.7%, respectively. Sprint time at 30 m also significantly improved by 1.9% in the HRW group in the last sprint. However, neither lactate concentrations nor ratings of perceived exertion were significantly different between HRW and placebo. Pre-exercise HRW supplementation is associated with an increased ability to reduce fatigue, especially during the later stages of repeated sprint exercise.", "conclusion": "However, neither lactate concentrations nor ratings of perceived exertion were significantly different between HRW and placebo. Pre-exercise HRW supplementation is associated with an increased ability to reduce fatigue, especially during the later stages of repeated sprint exercise." }, { "pmid": "35734974", "year": 2022, "title": "A randomized, placebo-controlled clinical trial of hydrogen/oxygen inhalation for non-alcoholic fatty liver disease", "title_en": null, "title_de": "Eine randomisierte, placebokontrollierte klinische Studie zur Wasserstoff/Sauerstoff-Inhalation bei nicht-alkoholischer Fettlebererkrankung", "journal": "Journal of Cellular and Molecular Medicine", "authors": "Tao et al.", "author_search": "tao tao", "doi": "10.1111/jcmm.17456", "doi_url": "https://doi.org/10.1111/jcmm.17456", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/35734974/", "url": "https://h2medicine.org/studies/study-tao-2022-oxygen-inhalation-nonalcoholic-fatty-liver/", "methods": [ "inhalation" ], "indications": [ "liver", "metabolic", "oxidative-stress" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2022 · Tao — A randomized, placebo-controlled clinical trial of hydrogen/oxygen inhalation for non-alcoholic fatty liver disease", "summary": "Hydrogen/oxygen inhalation improves blood lipid and liver values in non-alcoholic fatty liver — and measurably lowers liver fat content in moderate-to-severe cases. In a randomized, placebo-controlled trial (43 patients, 13 weeks), serum lipids and liver enzymes improved; ultrasound and CT showed less liver fat. Animal experiments point to increased hepatic autophagy as the mechanism. (J Cell Mol Med, 2022.)", "assessment": "A human study (RCT) plus mechanistic animal/cell evidence in one — a strong combination, because it not only shows an effect but also provides a plausible explanation (autophagy) and secures it with a blockade experiment. Relevant because NAFLD is a huge, growing health topic with no approved medication and H₂ was tested here in a real clinical indication. Important for honest communication: inhaled H₂/O₂ gas was used here, not H₂ drinking water — and the clearest imaging effects occurred in the more severe cases. This is no licence for general health claims, but a promising clinical signal. Limitation, stated honestly: moderate sample (n = 43), single-center, no active-comparator, China study; transfer to drinking-water products is not proven.", "abstract": "Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide with increasing incidence consistent with obesity, type 2 diabetes and cardiovascular diseases. No approved medication was currently available for NAFLD treatment. Molecular hydrogen (H2 ), an anti-oxidative, anti-inflammatory biomedical agent is proved to exhibit therapeutic and preventive effect in various diseases. The purpose of this study was to investigate the effect of hydrogen/oxygen inhalation on NAFLD subjects and explore the mechanism from the perspective of hepatocyte autophagy. We conducted a randomized, placebo-controlled clinical trial of 13-week hydrogen/oxygen inhalation (China Clinical Trial Registry [#ChiCTR-IIR-16009114]) including 43 subjects. We found that inhalation of hydrogen/oxygen improved serum lipid and liver enzymes. Significantly improved liver fat content detected by ultrasound and CT scans after hydrogen/oxygen inhalation was observed in moderate-severe cases. We also performed an animal experiment based on methionine and choline-deficient (MCD) diet-induced mice model to investigate effect of hydrogen on mouse NASH. Hydrogen/oxygen inhalation improved systemic inflammation and liver histology. Promoted autophagy was observed in mice inhaled hydrogen/oxygen and treatment with chloroquine blocked the beneficial effect of hydrogen. Moreover, molecular hydrogen inhibited lipid accumulation in AML-12 cells. Autophagy induced by palmitic acid (PA) incubation was further promoted by 20% hydrogen incubation. Addition of 3-methyladenine (3-MA) partially blocked the inhibitory effect of hydrogen on intracellular lipid accumulation. Collectively, hydrogen/oxygen inhalation alleviated NAFLD in moderate-severe patients. This protective effect of hydrogen was possibly by activating hepatic autophagy.", "conclusion": "Collectively, hydrogen/oxygen inhalation alleviated NAFLD in moderate-severe patients. This protective effect of hydrogen was possibly by activating hepatic autophagy." }, { "pmid": "36538554", "year": 2022, "title": "Acute pre-exercise hydrogen rich water intake does not improve running performance at maximal aerobic speed in trained track and field runners: A randomized, double-blind, placebo-controlled crossover study", "title_en": null, "title_de": "Akute Einnahme von wasserstoffreichem Wasser vor der Belastung verbessert die Laufleistung bei maximaler aerober Geschwindigkeit bei trainierten Leichtathletik-Läufern nicht: eine randomisierte, doppelblinde, placebokontrollierte Crossover-Studie", "journal": "PLoS ONE", "authors": "Valenta et al.", "author_search": "valenta valenta", "doi": "10.1371/journal.pone.0279307", "doi_url": "https://doi.org/10.1371/journal.pone.0279307", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36538554/", "url": "https://h2medicine.org/studies/study-valenta-2022-pre-exercise-maximal-aerobic-speed-runners/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2022 · Valenta — Acute pre-exercise hydrogen rich water intake does not improve running performance at maximal aerobic speed in trained track and field runners: A randomized, double-blind, placebo-controlled crossover study", "summary": "Hydrogen-rich water immediately before running gives trained runners no performance advantage. In this randomized double-blind placebo crossover study (24 trained runners), the acute intake of 1260 ml of HRW had no effect whatsoever on time to exhaustion, lactate, heart rate or oxygen uptake. (PLoS ONE, 2022 — an honest null finding for acute intake.)", "assessment": "An important counterweight in the database: this cleanly designed null finding guards against overreach. For us this means being honest in the sport context — H₂ water is not an acute „energy shot“ before competition. The benefit other studies show (less muscle damage, better recovery) tends to arise with regular use and concerns endpoints other than pure immediate endurance performance. It is exactly this distinction that makes the communication credible. Limitation, stated honestly: it examines only the acute single dose before one specific, very short maximal test (~3.5 min); young male runners; says nothing about chronic intake or other exertion profiles.", "abstract": "PURPOSE: This study investigated the effects of acute, pre-exercise, hydrogen rich water (HRW) ingestion on running time to exhaustion at maximal aerobic speed in trained track and field runners. METHODS: Twenty-four, male runners aged 17.5 ± 1.8 years, with body mass index = 21.0 ± 1.3 kg⋅m-2, and maximal oxygen uptake = 55.0 ± 4.6 ml⋅kg-1⋅min-1 (mean ± standard deviation) participated in this randomized, double-blind, placebo-controlled crossover study. All runners ingested 1260 ml of HRW which was divided into four doses and taken at 120 min (420 ml), 60 min (420 ml), 30 min (210 ml), and 10 min (210 ml) prior to exercise. The running protocol consisted of three phases: warm-up performed at 10 km⋅h-1 for 3 min, followed by a transition phase performed at an individually determined speed (10 km⋅h-1 + maximal aerobic speed)/2 for 1 min, and finally the third phase performed at individual maximal aerobic speed until exhaustion. Time to exhaustion, cardiorespiratory variables, and post-exercise blood lactate concentration were measured. RESULTS: When running to exhaustion at maximal aerobic speed, compared with placebo, HRW had no significant effects on the following variables: time to exhaustion (217 ± 49 and 227 ± 53 s, p = 0.20), post-exercise blood lactate concentration (9.9 ± 2.2 and 10.1 ± 2.0 mmol⋅L-1, p = 0.42), maximal heart rate (186 ± 9 and 186 ± 9 beats⋅min-1, p = 0.80), and oxygen uptake (53.1 ± 4.5 and 52.2 ± 4.7 ml⋅kg-1⋅min-1, p = 0.33). No variable assessed as a candidate moderator was significantly correlated with time to exhaustion (Spearman's correlation coefficients ranged from -0.28 to 0.30, all p ≥ 0.16). CONCLUSIONS: Pre-exercise administration of 1260 ml of HRW showed no ergogenic effect on running performance to exhaustion at maximal aerobic speed in trained track and field runners.", "conclusion": "Pre-exercise administration of 1260 ml of HRW showed no ergogenic effect on running performance to exhaustion at maximal aerobic speed in trained track and field runners." }, { "pmid": "36235628", "year": 2022, "title": "The Acute Effects of a Single Dose of Molecular Hydrogen Supplements on Responses to Ergogenic Adjustments during High-Intensity Intermittent Exercise in Humans", "title_en": null, "title_de": "Die akuten Effekte einer Einzeldosis molekularer Wasserstoff-Supplemente auf die Reaktionen ergogener Anpassungen während hochintensiver intermittierender Belastung beim Menschen", "journal": "Nutrients", "authors": "Alharbi et al.", "author_search": "alharbi alharbi", "doi": "10.3390/nu14193974", "doi_url": "https://doi.org/10.3390/nu14193974", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36235628/", "url": "https://h2medicine.org/studies/study-alharbi-2022-single-dose-ergogenic-intermittent-exercise/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise", "oxidative-stress" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2022 · Alharbi — The Acute Effects of a Single Dose of Molecular Hydrogen Supplements on Responses to Ergogenic Adjustments during High-Intensity Intermittent Exercise in Humans", "summary": "A single dose of molecular hydrogen before high-intensity interval training raises peak power and improves muscle oxygen supply. In this randomized double-blind crossover study (10 trained subjects), peak power in the first HIIT bout was significantly higher with H₂ than with placebo (839 vs. 816 W, p = 0.001), with better O₂ extraction in the muscle. (Nutrients, 2022.)", "assessment": "Important in the overall picture of the database: together with the Valenta null finding (endurance running, no effect), a differentiated picture emerges — H₂ seems to do something more in high-intensity, anaerobic training than in moderate aerobic endurance exertion. This nuance is exactly what makes a serious, engineering-honest database: no blanket „H₂ makes you faster“, but context-dependent differentiation. A useful building block for sport communication. Limitation, stated honestly: very small sample (n = 10), only an acute single dose, the H₂ amount at 2.544 µg is very small, the difference in peak power is small (23 W), and the authors phrase it deliberately cautiously („might“). Hence evidence level 2.", "abstract": "This research examined the effects of single-dose molecular hydrogen (H2) supplements on acid-base status and local muscle deoxygenation during rest, high-intensity intermittent training (HIIT) performance, and recovery. Ten healthy, trained subjects in a randomized, double-blind, crossover design received H2-rich calcium powder (HCP) (1500 mg, containing 2.544 μg of H2) or H2-depleted placebo (1500 mg) supplements 1 h pre-exercise. They performed six bouts of 7 s all-out pedaling (HIIT) at 7.5% of body weight separated by 40 s pedaling intervals, followed by a recovery period. Blood gases' pH, PCO2, and HCO3- concentrations were measured at rest. Muscle deoxygenation (deoxy[Hb + Mb]) and tissue O2 saturation (StO2) were determined via time-resolved near-infrared spectroscopy in the vastus lateralis (VL) and rectus femoris (RF) muscles from rest to recovery. At rest, the HCP group had significantly higher PCO2 and HCO3- concentrations and a slight tendency toward acidosis. During exercise, the first HIIT bout's peak power was significantly higher in HCP (839 ± 112 W) vs. Placebo (816 ± 108 W, p = 0.001), and HCP had a notable effect on significantly increased deoxy[Hb + Mb] concentration during HIIT exercise, despite no differences in heart rate response. The HCP group showed significantly greater O2 extraction in VL and microvascular (Hb) volume in RF during HIIT exercise. The HIIT exercise provided significantly improved blood flow and muscle reoxygenation rates in both the RF and VL during passive recovery compared to rest in all groups. The HCP supplement might exert ergogenic effects on high-intensity exercise and prove advantageous for improving anaerobic HIIT exercise performance.", "conclusion": "The HIIT exercise provided significantly improved blood flow and muscle reoxygenation rates in both the RF and VL during passive recovery compared to rest in all groups. The HCP supplement might exert ergogenic effects on high-intensity exercise and prove advantageous for improving anaerobic HIIT exercise performance." }, { "pmid": "36432562", "year": 2022, "title": "Effects of Intestinal Bacterial Hydrogen Gas Production on Muscle Recovery following Intense Exercise in Adult Men: A Pilot Study", "title_en": null, "title_de": "Effekte der intestinalen bakteriellen Wasserstoffgas-Produktion auf die Muskelerholung nach intensiver Belastung bei erwachsenen Männern: eine Pilotstudie", "journal": "Nutrients", "authors": "Eda et al.", "author_search": "eda eda", "doi": "10.3390/nu14224875", "doi_url": "https://doi.org/10.3390/nu14224875", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36432562/", "url": "https://h2medicine.org/studies/study-eda-2022-intestinal-bacterial-gas-muscle-recovery/", "methods": [], "indications": [ "sports-exercise", "oxidative-stress" ], "evidence_level": 3, "human": true, "therapeutic": false, "h2category": "byproduct", "headline": "2022 · Eda — Effects of Intestinal Bacterial Hydrogen Gas Production on Muscle Recovery following Intense Exercise in Adult Men: A Pilot Study", "summary": "A drink that stimulates gut bacteria to produce hydrogen can reduce muscle soreness and oxidative stress after intense exercise. In this double-blind crossover pilot study, after the H₂-generating drink — unlike after placebo — no rise in muscle soreness and oxidative DNA damage (8-OHdG) occurred; more breath hydrogen went hand in hand with less oxidation damage. (Nutrients, 2022 — endogenous H₂ as a new recovery strategy.)", "assessment": "This study is relevant because it confirms the H₂ principle from another angle: it is the hydrogen molecule itself that works — whether from the glass, from the inhaler or from one's own gut. The negative correlation between breath hydrogen and oxidation damage is a mechanistically strong argument that H₂ is the active factor and not a side effect. After careful review we accepted this study: hydrogen here is not merely an incidental covariate but the deliberately induced and studied intervention (the drink is designed for exactly that). For us it underpins the antioxidant core thesis. Limitation, stated honestly: pilot study with small sample, indirect H₂ source (dependent on individual gut flora), mechanism and dosing not conclusively clarified — hence evidence level 2, not 3.", "abstract": "This study aimed to examine the effects of hydrogen gas (H2) produced by intestinal microbiota on participant conditioning to prevent intense exercise-induced damage. In this double-blind, randomized, crossover study, participants ingested H2-producing milk that induced intestinal bacterial H2 production or a placebo on the trial day, 4 h before performing an intense exercise at 75% maximal oxygen uptake for 60 min. Blood marker levels and respiratory variables were measured before, during, and after exercise. Visual analog scale scores of general and lower limb muscle soreness evaluated were 3.8- and 2.3-fold higher, respectively, on the morning after treatment than that before treatment during the placebo trial, but not during the test beverage consumption. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations and production rates significantly increased with placebo consumption; no changes were observed with test beverage consumption. After exercise, relative blood lactate levels with H2-producing milk consumption were lower than those with placebo consumption. A negative correlation was observed between the variation of 8-OHdG and the area under the curve (AUC) of breath H2 concentrations. Lipid oxidation AUC was 1.3-fold higher significantly with H2-producing milk than with placebo consumption. Conclusively, activating intestinal bacterial H2 production by consuming a specific beverage may be a new strategy for promoting recovery and conditioning in athletes frequently performing intense exercises.", "conclusion": "Lipid oxidation AUC was 1.3-fold higher significantly with H2-producing milk than with placebo consumption. Conclusively, activating intestinal bacterial H2 production by consuming a specific beverage may be a new strategy for promoting recovery and conditioning in athletes frequently performing intense exercises." }, { "pmid": "36743938", "year": 2022, "title": "Effectiveness and safety of hydrogen inhalation as an adjunct treatment in Chinese type 2 diabetes patients: A retrospective, observational, double-arm, real-life clinical study.", "title_en": null, "title_de": "Wirksamkeit und Sicherheit der Wasserstoff-Inhalation als Zusatzbehandlung bei chinesischen Typ-2-Diabetes-Patienten: eine retrospektive, beobachtende, zweiarmige Real-Life-Studie", "journal": "Frontiers in Endocrinology", "authors": "Zhao et al.", "author_search": "zhao zhao", "doi": "10.3389/fendo.2022.1114221", "doi_url": "https://doi.org/10.3389/fendo.2022.1114221", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36743938/", "url": "https://h2medicine.org/studies/study-zhao-2022-inhalation-type-2-diabetes-adjunct/", "methods": [ "inhalation" ], "indications": [ "diabetes", "metabolic", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2022 · Zhao — Effectiveness and safety of hydrogen inhalation as an adjunct treatment in Chinese type 2 diabetes patients: A retrospective, observational, double-arm, real-life clinical study", "summary": "Hydrogen inhalation as an adjunct improved blood sugar control in type 2 diabetes. In a large real-life study (n = 1,088), over 6 months the H₂ group lowered long-term blood sugar HbA1c more (−0.94% vs. −0.46%) and had fewer side effects — all values p (Frontiers in Endocrinology, 2022.)", "assessment": "One of the strongest human signals for H₂ in type 2 diabetes — above all because of the case number unusually large for this field (n = 1,088) and the consistent, highly significant effect across several metabolic parameters. Diabetes is a commercially and medically highly relevant indication; the data support positioning H₂ as an adjunct therapy. Limitation, stated honestly: it is a retrospective observational study without randomization — despite propensity-score matching, residual confounding and selection effects remain possible (those who inhale may be more health-conscious/adherent). Causal proof would require a prospective RCT. As a complementary, low-side-effect measure alongside standard medical therapy, however, the signal is remarkably robust.", "abstract": "AIM: To analyze the effectiveness and safety of hydrogen inhalation (HI) therapy as an adjunct treatment in Chinese type 2 diabetes mellitus (T2DM) patients in a real-life clinical setting. METHODS: This observational, non-interventional, retrospective, double-arm, 6-month clinical study included T2DM patients receiving conventional anti-diabetes medication with or without HI initiation from 2018 to 2021. Patients were assigned to the HI group or non-HI group (control group) after 1:1 propensity score matching (PSM). The mean change in glycated hemoglobin (HbA1c) after 6 months in different groups was evaluated primarily. The secondary outcome was composed of the mean change of fasting plasma glucose (FPG), weight, lipid profile, and homeostasis model assessment. Logistics regression was performed to evaluate the likelihood of reaching different HbA1c levels after 6-month treatment between the groups. Adverse event (AE) was also evaluated in patients of both groups. RESULTS: In total, 1088 patients were selected into the analysis. Compared to the control group, subjects in HI group maintained greater improvement in the level of HbA1c (-0.94% vs -0.46%), FPG (-22.7 mg/dL vs -11.7 mg/dL), total cholesterol (-12.9 mg/dL vs -4.4 mg/dL), HOMA-IR (-0.76 vs -0.17) and HOMA-β (8.2% vs 1.98%) with all p< 0.001 post the treatment. Logistics regression revealed that the likelihood of reaching HbA1c< 7%, ≥ 7% to< 8% and > 1% reduction at the follow-up period was higher in the HI group, while patients in the control group were more likely to attain HbA1c ≥ 9%. Patients in HI group was observed a lower incidence of several AEs including hypoglycemia (2.0% vs 6.8%), vomiting (2.6% vs 7.4%), constipation (1.7% vs 4.4%) and giddiness (3.3% vs 6.3%) with significance in comparison to the control group. CONCLUSION: HI as an adjunct therapy ameliorates glycemic control, lipid metabolism, insulin resistance and AE incidence of T2DM patients after 6-month treatment, presenting a noteworthy inspiration to existing clinical diabetic treatment.", "conclusion": "HI as an adjunct therapy ameliorates glycemic control, lipid metabolism, insulin resistance and AE incidence of T2DM patients after 6-month treatment, presenting a noteworthy inspiration to existing clinical diabetic treatment." }, { "pmid": "36334558", "year": 2022, "title": "Research on red tide short-time prediction using GRU network model based on multi-feature Factors--A case in Xiamen sea area.", "title_en": null, "title_de": "Kurzzeitvorhersage von Rote-Tide-Ereignissen mittels GRU-Netzwerkmodell auf Basis von Multi-Merkmal-Faktoren — Fallstudie im Seegebiet Xiamen", "journal": "Marine environmental research", "authors": "Xiao et al.", "author_search": "xiao xiao", "doi": "10.1016/j.marenvres.2022.105727", "doi_url": "https://doi.org/10.1016/j.marenvres.2022.105727", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36334558/", "url": "https://h2medicine.org/studies/study-xiao-2022-research-red-tide-short/", "methods": [ "unspecified" ], "indications": [ "fundamentals-safety" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2022 · Xiao et al. — Red Tide Short-Time Prediction Using GRU Network Model Based on Multi-Feature Factors: A Case Study in Xiamen Sea Area", "summary": "This study uses machine learning — specifically a Gated Recurrent Unit (GRU) neural network — to predict red tide events in a Chinese coastal region up to 6 hours in advance, achieving accuracy rates above 92%. Among the most influential predictive factors identified are chlorophyll-a, dissolved oxygen, and the potential of hydrogen (pH). The research is an environmental monitoring and forecasting study, unrelated to therapeutic hydrogen applications. (Marine Environmental Research, 2022.)", "assessment": "This is a theory/computational study (environmental informatics). It has no relevance to molecular hydrogen therapy or health research. The term „hydrogen” in the dataset refers solely to the pH scale (potential of hydrogen) as an ocean-chemistry measurement variable. The study is technically sound for its domain but is out of scope for any H₂-medicine database. Honest note: This study appears here due to keyword matching on „hydrogen” in its methods fields, not because it researches H₂ as a therapeutic or biological agent.", "abstract": "Red tide caused severe impacts on marine fisheries, ecology, economy and human life safety. The formation mechanism of the red tide is rather complicated; thus, red tide prediction and forecasting have long been a research hotspot around the globe. This study collected ocean monitoring data before and after the occurrence of red tides in Xiamen sea area from 2009 to 2017. The Pearson correlation coefficient method was used to obtain the associated factors of red tide occurrence, including water temperature, saturated dissolved oxygen, dissolved oxygen, chlorophyll-aand potential of hydrogen. Then, we built a short-time red tide prediction model based on the combination of multiple feature factors. chlorophyll-a, dissolved oxygen, saturated dissolved oxygen, potential of hydrogen, water temperature, salinity, turbidity, wind speed, wind direction and Air pressure were used as the input variables, building a short-time prediction model based on the combination of multiple feature factors to forecast red tide in the next 6 h by using the monitoring data. The accuracy of different forecast models with different feature combinations was compared. Results show that the distinguishing factors which have the most significant influence on red tide prediction in Xiamen are chlorophyll-a, dissolved oxygen, saturated dissolved oxygen, potential of hydrogen, and water temperature. the convergence speed of the Gated Recurrence Unit (GRU) prediction model based on the main feature factor proposed in this paper was faster and obtained the expected result, and the accuracy rates of the buoys are above 92%. The research shows the feasibility to use GRU network model to predict the occurrence of red tide with multi-feature factors as input parameters. the paper provides an effective method for the red tide early warning in Xiamen sea area.", "conclusion": "The research shows the feasibility to use GRU network model to predict the occurrence of red tide with multi-feature factors as input parameters. the paper provides an effective method for the red tide early warning in Xiamen sea area." }, { "pmid": "36239123", "year": 2022, "title": "A bio-inspired, ultra-tough, high-sensitivity, and anti-swelling conductive hydrogel strain sensor for motion detection and information transmission.", "title_en": null, "title_de": "Bioinspirierter, ultrazäher, hochempfindlicher und quellungsresistenter leitfähiger Hydrogel-Dehnungssensor für Bewegungserkennung und Informationsübertragung", "journal": "Materials horizons", "authors": "Di et al.", "author_search": "di di", "doi": "10.1039/d2mh00456a", "doi_url": "https://doi.org/10.1039/d2mh00456a", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36239123/", "url": "https://h2medicine.org/studies/study-di-2022-bio-inspired-ultra-tough/", "methods": [ "unspecified" ], "indications": [ "sports-exercise" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2022 · Di et al. — A Bio-Inspired, Ultra-Tough, High-Sensitivity, and Anti-Swelling Conductive Hydrogel Strain Sensor for Motion Detection and Information Transmission", "summary": "Researchers developed a bio-inspired conductive hydrogel with exceptional mechanical toughness (elongation >2000%), high sensitivity, and resistance to swelling — enabling its use as a wearable strain sensor for motion detection and Morse-code information encryption. The material exploits hydrogen bonding as one of multiple non-covalent interactions to achieve its properties. This is a materials science study with no connection to therapeutic molecular hydrogen (H₂). (Materials Horizons, 2022.)", "assessment": "This is a materials science / computational-experimental study with no connection to molecular hydrogen therapy or H₂ biology. „Hydrogen” in this paper refers exclusively to hydrogen bonds — a ubiquitous intermolecular interaction in polymer chemistry. The study is technically sound and innovative in its field (wearable electronics), but is out of scope for any therapeutic H₂ research database. Honest note: This study appears due to keyword matching on „hydrogen” in polymer-science contexts, not because it investigates H₂ as a therapeutic agent.", "abstract": "Conductive hydrogels are excellent candidates for the next-generation wearable materials and are being extensively investigated for their potential use in health monitoring devices, human-machine interfaces, and other fields. However, their relatively low mechanical strength and performance degradation due to swelling have presented challenges in their practical application. Inspired by the multiscale heterogeneous architecture of biological tissue, a dynamic cross-linked, ultra-tough, and high-sensitivity hydrogel with a swelling resistance characteristic was fabricated by the principle of multiple non-covalent interaction matching and a step-by-step construction strategy. A heterogeneous structure was constructed by the combination of a 'soft' hydrophobic-conjugated micro-region structural domain with inter/intra-molecular hydrogen bonding and π-π stacking along with 'rigid' cross-linking via strong ionic coordination interactions. Reversible cross-linking synergies and variations in the content of rigid and flexible components guaranteed the hydrogel to undergo flexible and efficient modulation of the structures and gain excellent mechanics, including elongation at break (>2000%), toughness (∼60 MJ m-3), and recovery (>88%). Notably, hydrogels displayed good anti-swelling properties even in solutions with different pH (pH 2-11) and solvents. Moreover, the hydrogel further exhibited fast response (47.4 ms) and high sensitivity due to the presence of dynamic ions (Fe3+, Na+, and Cl-); therefore, it was assembled into a sensor to detect various human motions and used as a signal transmitter for the encryption and decryption of information according to Morse code. This study provides basis for the development of a variety of robust and flexible conductive hydrogels with multifunctional sensing applications in next-generation wearable devices.", "conclusion": "Moreover, the hydrogel further exhibited fast response (47.4 ms) and high sensitivity due to the presence of dynamic ions (Fe3+, Na+, and Cl-); therefore, it was assembled into a sensor to detect various human motions and used as a signal transmitter for the encryption and decryption of information according to Morse code. This study provides basis for the development of a variety of robust and fl" }, { "pmid": "36210415", "year": 2022, "title": "Dynamics of Metabolic and Oxidative Parameters of Erythrocytes during Treatment of Chronic Heart Failure with Molecular Hydrogen.", "title_en": null, "title_de": "Dynamik metabolischer und oxidativer Parameter von Erythrozyten während der Behandlung der chronischen Herzinsuffizienz mit molekularem Wasserstoff.", "journal": "Bulletin of experimental biology and medicine", "authors": "Deryugina et al.", "author_search": "deryugina deryugina", "doi": "10.1007/s10517-022-05595-z", "doi_url": "https://doi.org/10.1007/s10517-022-05595-z", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36210415/", "url": "https://h2medicine.org/studies/study-deryugina-2022-dynamics-metabolic-oxidative-parameters/", "methods": [ "inhalation" ], "indications": [ "cardiovascular", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2022 · Deryugina — Dynamics of Metabolic and Oxidative Parameters of Erythrocytes during Treatment of Chronic Heart Failure with Molecular Hydrogen.", "summary": "In patients with chronic heart failure, inhaling 2% molecular hydrogen — either once or repeatedly over five days — improved red blood cell energy metabolism, reduced oxidative stress markers, and enhanced antioxidant enzyme activity. Repeated inhalation produced stronger effects, suggesting a dose-accumulation benefit. (Bulletin of Experimental Biology and Medicine, 2022.)", "assessment": "This is a small mechanistic study with clinically relevant endpoints in a well-defined disease cohort (CHF). The erythrocyte parameters chosen (2,3-DPG, ATP, MDA, catalase) give a multi-dimensional picture of both energy metabolism and oxidative stress. The repeated-inhalation advantage is biologically plausible. Limitations: the paper is from a Russian journal (Bulletin of Experimental Biology and Medicine) — sample size, randomization details, and control conditions are not fully elaborated in the available abstract; no functional cardiac endpoints (ejection fraction, walk distance) are reported; the study design details (n, control group design, patient characteristics) are not specified. The recommendation to use H₂ against myocardial ischaemia is speculative without larger controlled trials. Nonetheless, the erythrocyte mechanism is an underexplored area of H₂ cardiology and this paper offers a useful mechanistic hypothesis.", "abstract": "We studied the effect of molecular hydrogen (H2) on the content of 2,3-diphosphoglyceric acid (2,3-DPG), ATP, malondialdehyde, and catalase activity in erythrocytes in chronic heart failure. Inhalation of 2% molecular hydrogen H2 was carried out for 40 min repeatedly (5 days) or once. Inhalation of H2 caused an increase in ATP concentration in both research groups, but was more pronounced after repeated inhalation. The content of 2,3-DPG increased after repeated exposure to H2. The increase in metabolic activity under the effect of H2 was accompanied by a decrease in malondialdehyde concentration and an increase in catalase activity. Thus, the application of H2 in chronic heart failure reduced oxidative stress and improved metabolism of erythrocytes, which contributes to improvement of microcirculation. This allows us to recommend H2 for protection against ischemic and reperfusion damage to the myocardium.", "conclusion": "Thus, the application of H2 in chronic heart failure reduced oxidative stress and improved metabolism of erythrocytes, which contributes to improvement of microcirculation. This allows us to recommend H2 for protection against ischemic and reperfusion damage to the myocardium." }, { "pmid": "36190308", "year": 2022, "title": "Using a high-throughput, whole-cell hydrogenase assay to identify potential small molecule inhibitors of [NiFe]-hydrogenase.", "title_en": null, "title_de": "Verwendung eines Hochdurchsatz-Ganzzell-Hydrogenase-Assays zur Identifizierung potenzieller niedermolekularer Inhibitoren der [NiFe]-Hydrogenase", "journal": "Metallomics : integrated biometal science", "authors": "Sebastiampillai et al.", "author_search": "sebastiampillai sebastiampillai", "doi": "10.1093/mtomcs/mfac073", "doi_url": "https://doi.org/10.1093/mtomcs/mfac073", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36190308/", "url": "https://h2medicine.org/studies/study-sebastiampillai-2022-high-throughput-whole-cell/", "methods": [ "unspecified" ], "indications": [ "sports-exercise" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2022 · Sebastiampillai et al. — Using a High-Throughput, Whole-Cell Hydrogenase Assay to Identify Potential Small Molecule Inhibitors of [NiFe]-Hydrogenase", "summary": "This in-vitro study developed a high-throughput screening assay to identify small molecules that could inhibit [NiFe]-hydrogenase enzymes — which certain human pathogens such as E. coli and H. pylori use to metabolise molecular hydrogen for energy. Iodoquinol was identified as a potential candidate, though follow-up assays revealed confounding effects. This is a microbiology / antimicrobial resistance study, not a therapeutic hydrogen study. (Metallomics, 2022.)", "assessment": "This is an in-vitro microbiology study. It does not study therapeutic H₂ for humans — rather, it investigates how to block bacteria from using H₂ as fuel. The research is relevant to antimicrobial drug development. The lead compound (iodoquinol) showed confounding results, illustrating the difficulty of whole-cell screening assays. Honest limitation: No human or animal data; results apply only to bacterial cell cultures. This study should not be interpreted as evidence for or against H₂ therapy in humans.", "abstract": "[NiFe]-hydrogenases are used by several human pathogens to catalyze the reversible conversion between molecular hydrogen and protons and electrons. Hydrogenases provide an increased metabolic flexibility for pathogens, such as Escherichia coli and Helicobacter pylori, by allowing the use of molecular hydrogen as an energy source to promote survival in anaerobic environments. With the rise of antimicrobial resistance and the desire for novel therapeutics, the [NiFe]-hydrogenases are alluring targets. Inhibiting the nickel insertion pathway of [NiFe]-hydrogenases is attractive as this pathway is required for the generation of functional enzymes and is orthogonal to human biochemistry. In this work, nickel availability for the production and function of E. coli [NiFe]-hydrogenase was explored through immunoblot and activity assays. Whole-cell hydrogenase activities were assayed in high throughput against a small molecule library of known bioactives. Iodoquinol was identified as a potential inhibitor of the nickel biosynthetic pathway of [NiFe]-hydrogenase through a two-step screening process, but further studies with immunoblot assays showed confounding effects dependent on the cell growth phase. This study highlights the significance of considering the growth phenotype for whole-cell based assays overall and its effects on various cellular processes influenced by metal trafficking and homeostasis.", "conclusion": "Iodoquinol was identified as a potential inhibitor of the nickel biosynthetic pathway of [NiFe]-hydrogenase through a two-step screening process, but further studies with immunoblot assays showed confounding effects dependent on the cell growth phase. This study highlights the significance of considering the growth phenotype for whole-cell based assays overall and its effects on various cellular p" }, { "pmid": "36167814", "year": 2022, "title": "Photocatalytic glucose depletion and hydrogen generation for diabetic wound healing.", "title_en": null, "title_de": "Photokatalytische Glukosedepletion und Wasserstofferzeugung zur diabetischen Wundheilung", "journal": "Nature communications", "authors": "Chen et al.", "author_search": "chen chen", "doi": "10.1038/s41467-022-33475-7", "doi_url": "https://doi.org/10.1038/s41467-022-33475-7", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36167814/", "url": "https://h2medicine.org/studies/study-chen-2022-photocatalytic-glucose-depletion-generation/", "methods": [ "bath-topical", "drinking-hrw" ], "indications": [ "diabetes", "skin-aging", "joints-rheumatology", "immune-system" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2022 · Chen et al. — Photocatalytic Glucose Depletion and Hydrogen Generation for Diabetic Wound Healing", "summary": "Researchers engineered hydrogen-incorporated titanium oxide nanorods that, under visible light, simultaneously deplete glucose and generate molecular hydrogen (H₂) at diabetic wound sites — addressing both the hyperglycaemic microenvironment and chronic inflammation. In preclinical models, the photocatalytic nanoparticles significantly promoted diabetic wound closure by reducing glycation end products and inhibiting apoptosis of skin cells. This is an in-vitro and animal study — results have not yet been validated in humans. (Nature Communications, 2022.)", "assessment": "This is a preclinical in-vitro and animal study. The concept of photocatalytic H₂ generation at wound sites is scientifically innovative and mechanistically well-supported by the data presented. However, no human clinical evidence is provided. The nanoparticle approach raises unresolved questions about biocompatibility, long-term safety, light penetration in real wound tissue, and scalability. The paper should be read as proof-of-concept for a novel therapeutic approach, not as evidence of clinical efficacy in diabetic patients.", "abstract": "High-glucose microenvironment in the diabetic foot ulcer (DFU) causes excessive glycation and induces chronic inflammation, leading to the difficulty of DFU healing. Hydrogen-rich water bath can promote the healing of DFU in clinic by virtue of the anti-inflammatory effect of hydrogen molecules, but the long-term daily soaking counts against the formation of a scab and cannot change the high-glucose microenvironment, limiting the outcome of DFU therapy. In this work, photocatalytic therapy of diabetic wound is proposed for sustainable hydrogen generation and local glucose depletion by utilizing glucose in the high-glucose microenvironment as a sacrificial agent. Hydrogen-incorporated titanium oxide nanorods are developed to realize efficient visible light (VIS)-responsive photocatalysis for glucose depletion and hydrogen generation, achieving a high efficacy of diabetic wound healing. Mechanistically, local glucose depletion and hydrogen generation jointly attenuate the apoptosis of skin cells and promote their proliferation and migration by inhibiting the synthesis of advanced glycation end products and the expression of their receptors, respectively. The proposed VIS-photocatalytic strategy provides a solution for facile, safe and efficient treatment of DFU.", "conclusion": "Mechanistically, local glucose depletion and hydrogen generation jointly attenuate the apoptosis of skin cells and promote their proliferation and migration by inhibiting the synthesis of advanced glycation end products and the expression of their receptors, respectively. The proposed VIS-photocatalytic strategy provides a solution for facile, safe and efficient treatment of DFU." }, { "pmid": "36014314", "year": 2022, "title": "Dehydrochlorination of PCDDs on SWCN-Supported Ni10 and Ni13 Clusters, a DFT Study.", "title_en": null, "title_de": "Dehydrochlorierung von PCDDs an SWCN-getragenen Ni₁₀- und Ni₁₃-Clustern: Eine DFT-Studie", "journal": "Molecules (Basel, Switzerland)", "authors": "González et al.", "author_search": "gonzález gonzález", "doi": "10.3390/molecules27165074", "doi_url": "https://doi.org/10.3390/molecules27165074", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36014314/", "url": "https://h2medicine.org/studies/study-gonzalez-2022-dehydrochlorination-pcdds-swcn-supported/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2022 · González et al. — Dehydrochlorination of PCDDs on SWCN-Supported Ni₁₀ and Ni₁₃ Clusters: A DFT Study", "summary": "This computational chemistry study investigates how molecular hydrogen (H₂), assisted by nickel nanoclusters adsorbed on carbon nanotubes, can chemically break down polychlorinated dibenzo-p-dioxins (PCDDs) — one of the most toxic classes of environmental pollutants. Using density functional theory (DFT) calculations, the authors find that H₂-mediated dehalogenation is energetically feasible and could offer an alternative to high-temperature combustion for dioxin detoxification. This is a theoretical computational study with no biological or health application. (Molecules, 2022.)", "assessment": "This is a theoretical computational (DFT) study in environmental chemistry. It has no biological, medical, or therapeutic relevance to H₂ for human health. Molecular hydrogen here functions as a chemical reagent for dioxin degradation — not as a therapeutic gas. The findings are scientifically interesting for environmental remediation research but cannot be applied to any human health context. Honest note: This study is outside the scope of therapeutic H₂ research entirely.", "abstract": "Polychlorinated dibenzo-p-dioxins (PCDDs) are known to be a group of compounds of high toxicity for animals and, particularly, for humans. Given that the most common method to destroy these compounds is by high-temperature combustion, finding other routes to render them less toxic is of paramount importance. Taking advantage of the physisorption properties of nanotubes, we studied the reactions of atomic hydrogen on physisorbed PCDDs using DFT; likewise, we investigated the reaction of molecular hydrogen on PCDDs aided by Ni10 and Ni13 clusters adsorbed on single-wall carbon nanotubes. Because dihydrogen is an easily accessible reactant, we found these reactions to be quite relevant as dehydrohalogenation methods to address PCDD toxicity.", "conclusion": "Taking advantage of the physisorption properties of nanotubes, we studied the reactions of atomic hydrogen on physisorbed PCDDs using DFT; likewise, we investigated the reaction of molecular hydrogen on PCDDs aided by Ni10 and Ni13 clusters adsorbed on single-wall carbon nanotubes. Because dihydrogen is an easily accessible reactant, we found these reactions to be quite relevant as dehydrohalogena" }, { "pmid": "35970006", "year": 2022, "title": "Hydrogen production from urea in human urine using segregated systems.", "title_en": null, "title_de": "Wasserstofferzeugung aus Harnstoff im menschlichen Urin unter Verwendung getrennter Systeme", "journal": "Water research", "authors": "Asiain-Mira et al.", "author_search": "asiain-mira asiain-mira", "doi": "10.1016/j.watres.2022.118931", "doi_url": "https://doi.org/10.1016/j.watres.2022.118931", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/35970006/", "url": "https://h2medicine.org/studies/study-asiainmira-2022-production-urea-urine-segregated/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2022 · Asiain-Mira et al. — Hydrogen Production from Urea in Human Urine Using Segregated Systems", "summary": "This study demonstrates a novel process for recovering energy from human urine by extracting urea, decomposing it thermally into ammonia, and then converting ammonia to hydrogen gas (H₂) — a potential energy fuel. Energy balance modelling suggests a city of 160,000 inhabitants could produce 430 kg of H₂ daily through this approach. This is an environmental engineering and circular economy study; it has no connection to therapeutic hydrogen applications. (Water Research, 2022.)", "assessment": "This is an in-vitro / engineering study (wastewater treatment, sustainable energy). It has no relevance to therapeutic molecular hydrogen. H₂ produced here is a combustible fuel for energy generation — not hydrogen-rich water or inhaled H₂ for health purposes. The study is technically sound within its domain of circular economy and sustainable energy. Honest note: This study appears in an H₂-medicine context solely due to keyword overlap; its subject matter is environmental engineering.", "abstract": "Removal of nitrogen compounds through biological processes represents the highest energy consumption in conventional centralised wastewater treatment facilities. Alternatively, segregated systems, where wastewater is treated at its source, present the potential to provide value to nitrogen-rich compounds contained in wastewater like urea. This paper demonstrates the feasibility of a novel process to recover energy from human urine based on the pre-isolation of urea to decrease the energy requirements for its thermal decomposition compared to the conventional thermal treatment when in solution, followed by its decomposition into hydrogen. Herein, urea is separated from an aqueous solution by adsorption onto activated carbon. Thermal urea desorption and decomposition into ammonia and CO2 at 250 °C leads to full regeneration of the carbon, showing a constant adsorption capacity for at least 5 consecutive adsorption/desorption cycles. Finally, when the regeneration and urea decomposition step is coupled to an ammonia decomposition catalyst, hydrogen is produced to be used as an energy fuel. This process opens the door to a new way of circular economy by energy recovery from hydrogen-rich components in segregated wastewater streams. Preliminary energy balances show that the adoption of this energy recovery system in a city of 160,000 inhabitants would lead to a daily hydrogen production of 430 kg, with a net energy production of 2,500 kWh/day. In addition, such waste-to-energy process would lead to energy savings of 4,600 kWh/day in a conventional wastewater treatment plant reducing its energy consumption by around 35%.", "conclusion": "Preliminary energy balances show that the adoption of this energy recovery system in a city of 160,000 inhabitants would lead to a daily hydrogen production of 430 kg, with a net energy production of 2,500 kWh/day. In addition, such waste-to-energy process would lead to energy savings of 4,600 kWh/day in a conventional wastewater treatment plant reducing its energy consumption by around 35%." }, { "pmid": "35909288", "year": 2022, "title": "Narrative on Hydrogen Therapy and its Clinical Applications: Safety and Efficacy.", "title_en": null, "title_de": "Bericht über die Wasserstofftherapie und ihre klinischen Anwendungen: Sicherheit und Wirksamkeit", "journal": "Current pharmaceutical design", "authors": "Ahmad et al.", "author_search": "ahmad ahmad", "doi": "10.2174/1381612828666220728104200", "doi_url": "https://doi.org/10.2174/1381612828666220728104200", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/35909288/", "url": "https://h2medicine.org/studies/study-ahmad-2022-narrative-applications/", "methods": [ "unspecified" ], "indications": [ "neurology", "cardiovascular", "respiratory", "immune-system", "oxidative-stress", "fundamentals-safety" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2022 · Ahmad et al. — Narrative on Hydrogen Therapy and its Clinical Applications: Safety and Efficacy", "summary": "This narrative review surveys the growing body of evidence on molecular hydrogen (H₂) as a therapeutic agent across cardiovascular, respiratory, neurological, metabolic, and infectious diseases — summarising both its proposed mechanisms and current safety data. The authors highlight H₂'s anti-inflammatory, antioxidative, and cytoprotective properties while acknowledging that evidence remains preliminary and that large-scale controlled trials are still needed. (Current Pharmaceutical Design, 2022.)", "assessment": "This is a narrative review — it synthesises existing literature but does not add new clinical data. The scope is broad (cardiovascular, respiratory, neurological, metabolic, hematological, infectious diseases), which is both a strength (comprehensive overview) and a limitation (depth in any single area is limited). The authors are honest about the field's preliminary state. Limitations to note: narrative reviews are subject to selection bias; the paper does not perform a systematic search or meta-analysis. The optimism should be tempered by the fact that most supporting evidence remains preclinical. This is a useful orientation piece, not clinical proof of efficacy across the diseases listed.", "abstract": "Molecular hydrogen proved itself as a novel therapeutic candidate and has been thriving from the beginning with its potential clinical significance, higher affinity, and cellular integrity and permeability. Hydrogen Therapy (HT) has gained scientists' attention with the proven clinical ability to attenuate chronic inflammation, diminish oxidative stress, restrict apoptosis, minimize cellular injury, and refine tissue functioning. Therapeutic Implementation of H2 for disease prevention and treatment is a newly emerging field with limited knowledge available on formulations, tissue-specific effects, efficacy, and safety. This article will discuss HT's therapeutic potential for its efficacy and safety in cardiovascular, respiratory, hematological, metabolic, infectious, and neurodegenerative disorders. In addition to this, the molecular mechanisms and nanotechnological implications of hydrogen therapy will be discussed in detail. Finally, the article will provide insight into advancements and automation, future perspectives, and recommendations. There is a need to study and conduct higher-scale trials targeting personalized treatments under molecular and genetic vitals.", "conclusion": "Finally, the article will provide insight into advancements and automation, future perspectives, and recommendations. There is a need to study and conduct higher-scale trials targeting personalized treatments under molecular and genetic vitals." }, { "pmid": "35843727", "year": 2022, "title": "A potential clinical application of hydrogen-rich saline in patients with traumatic brain injury.", "title_en": null, "title_de": "Eine potenzielle klinische Anwendung von wasserstoffreicher Kochsalzlösung bei Patienten mit Schädel-Hirn-Trauma.", "journal": "Journal of pediatric surgery", "authors": "Benjamin et al.", "author_search": "benjamin benjamin", "doi": "10.1016/j.jpedsurg.2022.06.007", "doi_url": "https://doi.org/10.1016/j.jpedsurg.2022.06.007", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/35843727/", "url": "https://h2medicine.org/studies/study-benjamin-2022-application-saline-traumatic-brain/", "methods": [ "saline-iv" ], "indications": [ "neurology" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2022 · Benjamin — A potential clinical application of hydrogen-rich saline in patients with traumatic brain injury.", "summary": "This paper from the Journal of Pediatric Surgery explores the potential use of hydrogen-rich saline as a treatment for traumatic brain injury (TBI) — one of the most devastating and difficult-to-treat neurological emergencies, especially in pediatric patients. Hydrogen's antioxidant and anti-inflammatory properties are proposed as a mechanistic basis for neuroprotection. (Journal of Pediatric Surgery, 2022.)", "assessment": "This study addresses a high-priority clinical unmet need — effective neuroprotective treatments for TBI remain limited. Hydrogen-rich saline is a biologically plausible candidate given its known antioxidant and anti-inflammatory properties. Critical limitation: no abstract was available in the source data, making independent assessment of methodology, sample size, control design, endpoints, and outcomes impossible. Given publication in the Journal of Pediatric Surgery (2022), readers should consult the original paper (DOI: 10.1016/j.jpedsurg.2022.06.007) for full evaluation before drawing clinical conclusions.", "abstract": null, "conclusion": null }, { "pmid": "35705974", "year": 2022, "title": "Microbial hydrogen \"manufactory\" for enhanced gas therapy and self-activated immunotherapy via reduced immune escape.", "title_en": null, "title_de": "Mikrobielle Wasserstoff-„Manufaktur” für verbesserte Gastherapie und selbstaktivierte Immuntherapie durch reduziertes Immune Escape", "journal": "Journal of nanobiotechnology", "authors": "Yan et al.", "author_search": "yan yan", "doi": "10.1186/s12951-022-01440-7", "doi_url": "https://doi.org/10.1186/s12951-022-01440-7", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/35705974/", "url": "https://h2medicine.org/studies/study-yan-2022-microbial-manufactory-enhanced-self/", "methods": [ "unspecified" ], "indications": [ "cancer", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2022 · Yan et al. — Microbial Hydrogen „Manufactory” for Enhanced Gas Therapy and Self-Activated Immunotherapy via Reduced Immune Escape", "summary": "Researchers used live photosynthetic bacteria (PSB) as a biological H₂ „factory” to release sustained amounts of hydrogen at tumour sites, selectively disrupting the reactive oxygen species balance in cancer cells while simultaneously stimulating an anti-tumour immune response. Notably, this approach did not upregulate PD-L1 — a protein that helps tumours escape immune attack. This is a preclinical theory/animal study; no human data are available. (Journal of Nanobiotechnology, 2022.)", "assessment": "This is a preclinical theory/animal study. The concept of using living bacteria as H₂ generators for cancer therapy is scientifically creative and the mechanistic data are encouraging, particularly the PD-L1 finding. However, this is not a clinical study and has not been tested in humans. Key unknowns include long-term safety of intratumoral PSB injection, immune responses to the bacteria themselves, and scalability. The results should be understood as early-stage proof-of-concept, not as evidence of anti-cancer efficacy in humans.", "abstract": "BACKGROUND: As an antioxidant, hydrogen (H2) can selectively react with the highly toxic hydroxyl radical (·OH) in tumor cells to break the balance of reactive oxygen species (ROS) and cause oxidative stress. However, due to the high diffusibility and storage difficulty of hydrogen, it is impossible to achieve long-term release at the tumor site, which highly limited their therapeutic effect. RESULTS: Photosynthetic bacteria (PSB) release a large amount of hydrogen to break the balance of oxidative stress. In addition, as a nontoxic bacterium, PSB could stimulate the immune response and increase the infiltration of CD4+ and CD8+ T cells. More interestingly, we found that hydrogen therapy induced by our live PSB did not lead to the up-regulation of PD-L1 after stimulating the immune response, which could avoid the tumor immune escape. CONCLUSION: Hydrogen-immunotherapy significantly kills tumor cells. We believe that our live microbial hydrogen production system provides a new strategy for cancer hydrogen treatment combining with enhanced immunotherapy without up-regulating PD-L1.", "conclusion": "Hydrogen-immunotherapy significantly kills tumor cells. We believe that our live microbial hydrogen production system provides a new strategy for cancer hydrogen treatment combining with enhanced immunotherapy without up-regulating PD-L1." }, { "pmid": "35700582", "year": 2022, "title": "Hydrogen helps to ameliorate Staphylococcus aureus-induced mastitis in mice.", "title_en": null, "title_de": "Wasserstoff hilft, die durch Staphylococcus aureus induzierte Mastitis bei Mäusen zu lindern", "journal": "International immunopharmacology", "authors": "Geng et al.", "author_search": "geng geng", "doi": "10.1016/j.intimp.2022.108940", "doi_url": "https://doi.org/10.1016/j.intimp.2022.108940", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/35700582/", "url": "https://h2medicine.org/studies/study-geng-2022-helps-ameliorate-staphylococcus-aureus/", "methods": [ "unspecified" ], "indications": [ "cancer", "immune-system" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2022 · Geng et al. — Hydrogen Helps to Ameliorate Staphylococcus aureus-Induced Mastitis in Mice", "summary": "In a mouse model of bacterial mastitis, hydrogen-rich vitamin E glycerin (HR-VEG) applied topically to the mammary gland reduced tissue damage, inflammatory cytokines (TNF-α, IL-1β, IL-6), and bacterial load more effectively than regular vitamin E glycerin — by inhibiting the TLR2/Nod2-NF-κB/MAPK signalling cascade. These results are from animal experiments; therapeutic relevance to humans has not been established. (International Immunopharmacology, 2022.)", "assessment": "This is an animal study (mouse model). The findings are mechanistically coherent with the known anti-inflammatory biology of H₂. However, results from a mouse mastitis model cannot be directly translated to human therapy. The H₂ delivery format (topical hydrogen-rich vitamin E glycerin) is also specific to this experimental setting and not a commonly used H₂ administration route. This study contributes to the mechanistic understanding of H₂'s anti-inflammatory effects in infection-driven inflammation but is not clinical evidence.", "abstract": "Many studies have shown that hydrogen has anti-inflammatory and anti-oxidant effects. Because of its ability to quickly pass through cell membranes, hydrogen has become a hot spot in the research of inflammatory diseases. Vitamin E glycerin (VEG) and hydrogen-rich Vitamin E glycerin (HR-VEG) were prepared, aiming to explore their anti-inflammatory activities in mice mastitis induced by Staphylococcus aureus (S. aureus). In the early part of this study, the prepared vitamin E medium (VEM) and hydrogen-rich vitamin E medium (HR-VEM) were added to mammary epithelial cells infected with S. aureus. HR-VEM was found to be more effective in reducing the phosphorylation of p65 and p38 and in reducing the production of interleukin-1 beta (IL-1β) than VEM. Whereafter, the mice model of mastitis was established by injecting S. aureus from the mammary duct. Then VEG and HR-VEG were applied to the mammary gland for seven consecutive days. After that, the clinical symptoms, histopathology, bacterial load, inflammatory factors, as well as the related pathway were analyzed. The results showed that HR-VEG can more significantly alleviate the damage of mammary tissue than VEG, and reduce the production of tumor necrosis factor-alpha (TNF-α), IL-1β and interleukin 6 (IL-6). In addition, HR-VEG inhibited the TLR2 and Nod2 signaling pathways and reduced the phosphorylation level of MAPK and NF-κB signaling pathways in S. aureus-induced murine mastitis. This study indicates that hydrogen helps to ameliorate S. aureus-induced mastitis in mice through attenuating TLR2 and Nod2 mediated NF-κB and MAPK activation.", "conclusion": "This study indicates that hydrogen helps to ameliorate S. aureus-induced mastitis in mice through attenuating TLR2 and Nod2 mediated NF-κB and MAPK activation." }, { "pmid": "35675761", "year": 2022, "title": "Hydrogen-Rich Water as a Dietary Activator of Brown Adipose Tissue and UCP1?", "title_en": null, "title_de": "Wasserstoffreiches Wasser als diätetischer Aktivator von braunem Fettgewebe und UCP1?", "journal": "Annals of nutrition & metabolism", "authors": "Ostojic", "author_search": "ostojic ostojic", "doi": "10.1159/000525175", "doi_url": "https://doi.org/10.1159/000525175", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/35675761/", "url": "https://h2medicine.org/studies/study-ostojic-2022-dietary-activator-brown-adipose/", "methods": [ "drinking-hrw" ], "indications": [ "metabolic" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2022 · Ostojic — Hydrogen-Rich Water as a Dietary Activator of Brown Adipose Tissue and UCP1?", "summary": "This short theoretical communication poses the question of whether hydrogen-rich water (HRW) could activate brown adipose tissue (BAT) and the thermogenic protein UCP1 — and thereby contribute to fat metabolism and energy expenditure. The author proposes a mechanistic hypothesis based on existing H₂ biology and BAT physiology, but presents no new experimental data. The abstract is empty; this is a hypothesis/commentary piece. (Annals of Nutrition and Metabolism, 2022.)", "assessment": "This is a theoretical hypothesis/commentary with no experimental data available (the abstract is empty). The hypothesis — that HRW might activate BAT and UCP1 — is mechanistically plausible and scientifically interesting, but remains entirely speculative without supporting data. Honest limitation: This contribution cannot be assessed for scientific weight beyond the plausibility of its proposed mechanism. Readers should consult the full text (DOI: 10.1159/000525175) for any reasoning presented. No conclusions about efficacy can be drawn.", "abstract": null, "conclusion": null }, { "pmid": "35606529", "year": 2022, "title": "Radiographic features of magnesium-based bioabsorbable screw resorption in paediatric fractures.", "title_en": null, "title_de": "Radiographische Merkmale der Resorption von magnesiumbasierten bioresorbierbaren Schrauben bei pädiatrischen Frakturen", "journal": "Pediatric radiology", "authors": "Waelti et al.", "author_search": "waelti waelti", "doi": "10.1007/s00247-022-05383-x", "doi_url": "https://doi.org/10.1007/s00247-022-05383-x", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/35606529/", "url": "https://h2medicine.org/studies/study-waelti-2022-radiographic-features-magnesium-bioabsorbable/", "methods": [], "indications": [ "joints-rheumatology" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "byproduct", "headline": "2022 · Waelti — Radiographic features of magnesium-based bioabsorbable screw resorption in paediatric fractures", "summary": "When magnesium-based screws dissolve in bone, they release hydrogen gas — and that gas is perfectly normal, not a sign of infection. This retrospective radiographic study in 35 children maps how gas bubbles appear, where they travel, and when they disappear, helping radiologists and surgeons avoid misdiagnosis. (Pediatric Radiology, 2022.)", "assessment": "This is a well-executed retrospective imaging study with a clear and clinically useful message. Its contribution to the H₂ field is indirect: it documents that locally produced H₂ gas from implant resorption is safe and self-resolving in paediatric bone. Limitations: retrospective design, single-centre, no control group (by definition — all patients had magnesium screws), and the study cannot speak to therapeutic H₂ effects. The high screw breakage rate (45.7%) is a limitation of the implant technology itself and not H₂-related. Not a therapeutic efficacy study.", "abstract": "BACKGROUND: Resorption of magnesium-based alloy bioabsorbable screws produces hydrogen gas, which can be mistaken as a sign of infection and may affect the physis or fixed bone fragment. OBJECTIVE: We evaluated the temporal and spatial occurrence of gas and the occurrence of a breakage of the fixed bone fragment or screw following magnesium screw fixation. MATERIALS AND METHODS: Radiographs of paediatric patients treated with magnesium screws were retrospectively reviewed. Temporal occurrence and distribution of gas in the bone, the physis and soft tissues, breakage of the screw or fixed bone fragment and joint effusion were assessed. RESULTS: One hundred and three radiographs in 35 paediatric patients were reviewed (mean age: 10.6 years). Follow-up ranged from 1 to 730 days. Gas in the bone increases up to week 5, remains constant up to week 16 and then decreases. Gas in soft tissues, intra-articular gas and joint effusions gradually reduce over time. In 1/23 (4.3%) patients with an open physis, gas intrusion into the physis occurred. Breakage of the bone fragment fixated by the screw was observed in 4/35 (11.4%) patients within the first 6 weeks. Screw breakage was observed in 16/35 (45.7%) patients, with a median time to first detection of 300 days. CONCLUSION: Gas bubbles in bone and soft tissue are normal findings in the context of screw resorption and should not be confused with soft-tissue infection or osteomyelitis. Gas is rarely visible in the physis. Breakage of the fixed bone fragment and/or screw can occur.", "conclusion": "Gas bubbles in bone and soft tissue are normal findings in the context of screw resorption and should not be confused with soft-tissue infection or osteomyelitis. Gas is rarely visible in the physis. Breakage of the fixed bone fragment and/or screw can occur." }, { "pmid": "35605978", "year": 2022, "title": "Development of a Model System for Gas Cavity Formation Behavior of Magnesium Alloy Implantation.", "title_en": null, "title_de": "Entwicklung eines Modellsystems für das Verhalten der Gashohlraumbildung bei der Implantation von Magnesiumlegierungen", "journal": "ACS biomaterials science & engineering", "authors": "Yamamoto et al.", "author_search": "yamamoto yamamoto", "doi": "10.1021/acsbiomaterials.1c01429", "doi_url": "https://doi.org/10.1021/acsbiomaterials.1c01429", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/35605978/", "url": "https://h2medicine.org/studies/study-yamamoto-2022-development-model-system-cavity/", "methods": [ "inhalation", "bath-topical" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2022 · Yamamoto et al. — Development of a Model System for Gas Cavity Formation Behavior of Magnesium Alloy Implantation", "summary": "This study developed an in-vitro gelatin model to simulate and measure the hydrogen gas cavities that form in tissue when biodegradable magnesium (Mg) bone screws corrode — a known clinical challenge in orthopaedic surgery. The model accurately reproduced clinical gas cavity volumes and demonstrated that cavity size depends on the corrosion rate of the Mg alloy and its polymer coating thickness. This is a biomaterials engineering study; H₂ here is a by-product of metal corrosion, not a therapeutic agent. (ACS Biomaterials Science and Engineering, 2022.)", "assessment": "This is an in-vitro biomaterials engineering study. It has no relevance to therapeutic molecular hydrogen. H₂ here is an unwanted corrosion by-product in orthopaedic implants. The model is technically solid and validated against clinical data, making it useful for the Mg implant research community. Honest note: This study appears in an H₂-medicine context due to keyword overlap — its subject is surgical implant materials science, not health effects of administered H₂.", "abstract": "Clinical applications of magnesium (Mg)-based screws have reported gas cavity formation in the surrounding tissue, which sometimes delays the fixation of the bone fracture. The gas cavity formation is considered to depend on the balance between hydrogen generation by Mg corrosion reacting with water in the body fluid and its diffusion into the surrounding tissue by capillary flow. In order to understand the gas cavity formation behavior by Mg-based material implantation, we developed a new in vitro model system to recreate this cavity formation phenomenon: the hydrogen generation by corrosion and its diffusion into the medium. A model tissue is prepared by gelation of the cell culture medium in a sterile condition. The immersion of Mg alloy samples was performed under 5% CO2 atmosphere with periodic observation by X-ray computed tomography, which enabled us to observe gas cavity growth up to 28 d. For demonstrating the usefulness of our model system, Mg alloy samples with different corrosion rates were prepared by a biodegradable polymer coating. AZ31 screws were spin-coated by poly-l-lactide (PLLA) and classified into three groups by their coating thickness as 1.0 ± 0.0, 1.6 ± 0.2, and 2.0 ± 0.1 μm (ave. ± s.d.). Upon their immersion into the model tissue, the gas cavity volumes formed were 1.57 ± 0.23, 1.06 ± 0.22, and 0.38 ± 0.09 mm3/mm2 for 1.0, 1.6, and 2.0 μm coating samples, having the weight loss of 20.2 ± 2.93, 18.5 ± 2.84, and 11.3 ± 3.54 μg/mm2, respectively (ave. ± s.d.). This result clearly indicates the dependence of gas cavity formation on the corrosion rate of the sample. The gas cavity volume was only 3.3∼7.5% of the total hydrogen gas volume estimated based on the weight loss of the samples at 28 d, which is in the range of those calculated from the clinical report (3.2∼9.4% at 4w). This system can be an effective tool to investigate the gas cavity formation behavior and contribute to understand the mechanisms and controlling factors of this phenomenon.", "conclusion": "The gas cavity volume was only 3.3∼7.5% of the total hydrogen gas volume estimated based on the weight loss of the samples at 28 d, which is in the range of those calculated from the clinical report (3.2∼9.4% at 4w). This system can be an effective tool to investigate the gas cavity formation behavior and contribute to understand the mechanisms and controlling factors of this phenomenon." }, { "pmid": "35564808", "year": 2022, "title": "Short-Term Consumption of Hydrogen-Rich Water Enhances Power Performance and Heart Rate Recovery in Dragon Boat Athletes: Evidence from a Pilot Study.", "title_en": null, "title_de": "Kurzfristiger Konsum von wasserstoffreichem Wasser verbessert die Kraftleistung und die Herzfrequenzerholung bei Drachenboot-Athleten", "journal": "International journal of environmental research and public health", "authors": "Dong et al.", "author_search": "dong dong", "doi": "10.3390/ijerph19095413", "doi_url": "https://doi.org/10.3390/ijerph19095413", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/35564808/", "url": "https://h2medicine.org/studies/study-dong-2022-short-term-consumption-enhances/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise", "cardiovascular", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2022 · Dong — Short-Term Consumption of Hydrogen-Rich Water Enhances Power Performance and Heart Rate Recovery in Dragon Boat Athletes", "summary": "Seven days of hydrogen-rich water improved maximum power output and post-exercise heart rate recovery in competitive dragon boat athletes compared to placebo water. This small pilot RCT points to H₂ as a practical hydration strategy for endurance and power sports, while also noting the limits of a 9-person-per-group design. (International Journal of Environmental Research and Public Health, 2022.)", "assessment": "A promising but underpowered pilot study. The performance and recovery signal is consistent with other H₂ exercise studies, and the within-group heart-rate recovery difference is the most clinically meaningful finding. Limitations: n=9 per group, no H₂ concentration data for the water, unclear blinding quality, single sport and training context, no follow-up beyond day 8. The null findings on 500 m row prediction and rowing distance should be reported as clearly as the positive findings — the paper does so, which is a methodological credit. Treat as hypothesis-generating rather than conclusive.", "abstract": "(1) Background: Exercise that exceeds the body's accustomed load can lead to oxidative stress and increased fatigue during intense training or competition, resulting in decreased athletic performance and an increased risk of injury, and the new medicinal H2 may be beneficial as an antioxidant. Therefore, we explored the effect of short-term supplementation of hydrogen-rich water (HRW) on the work performance and fatigue recovery of dragon boat athletes after training. (2) Methods: Eighteen dragon boat athletes who trained for 4 h a day (2 h in the morning and 2 h in the afternoon) were divided into an HRW group (n = 9) and a placebo water (PW) group (n = 9), drinking HRW or PW for 7 days. Each participant completed 30 s rowing dynamometer tests, monitoring the heart rate at baseline (i.e., Day 1) and after the intervention (on Day 8). (3) Result: Drinking HRW increased the maximum power and average power of the 30 s rowing test and decreased the maximum heart rate during the period. After the rowing test, the HRW group's heart rate dropped significantly after 2 min of recovery, while the PW group's heart rate did not drop. There was no significant difference between the 30 s rowing distance and the predicted duration of rowing 500 m. (4) Conclusions: Drinking HRW in the short term can effectively improve the power performance of dragon boat athletes and is conducive to the recovery of the heart rate after exercise, indicating that HRW may be a suitable means of hydration for athletes.", "conclusion": "Drinking HRW in the short term can effectively improve the power performance of dragon boat athletes and is conducive to the recovery of the heart rate after exercise, indicating that HRW may be a suitable means of hydration for athletes." }, { "pmid": "35536023", "year": 2022, "title": "Metabolic Synergy between Human Symbionts Bacteroides and Methanobrevibacter.", "title_en": null, "title_de": "Metabolische Synergie zwischen den menschlichen Symbionten Bacteroides und Methanobrevibacter", "journal": "Microbiology spectrum", "authors": "Catlett et al.", "author_search": "catlett catlett", "doi": "10.1128/spectrum.01067-22", "doi_url": "https://doi.org/10.1128/spectrum.01067-22", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/35536023/", "url": "https://h2medicine.org/studies/study-catlett-2022-metabolic-synergy-between-symbionts/", "methods": [ "inhalation" ], "indications": [ "metabolic", "sports-exercise" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2022 · Catlett — Metabolic Synergy between Human Symbionts Bacteroides and Methanobrevibacter", "summary": "Two dominant gut microbes — Bacteroides thetaiotaomicron and the hydrogen-consuming archaeon Methanobrevibacter smithii — form a mutual metabolic partnership that depends on hydrogen gas. A controlled co-culture system revealed that when vitamin B12, hematin, and hydrogen are all abundant, the two microbes together outgrow what either achieves alone. This is a theoretical and in-vitro study; findings describe microbial relationships, not human health outcomes. (Microbiology Spectrum, 2022.)", "assessment": "This is a theory and in-vitro study — no humans, no animals, no clinical endpoints. Its value lies in illuminating how gut-derived hydrogen gas functions as a metabolic currency between microbial species, which is background knowledge relevant for understanding the microbiome's hydrogen economy. No direct conclusions about human health or hydrogen supplementation can be drawn. The machine-learning-assisted co-culture platform itself is a methodological contribution for future gut-ecology research.", "abstract": "Trophic interactions between microbes are postulated to determine whether a host microbiome is healthy or causes predisposition to disease. Two abundant taxa, the Gram-negative heterotrophic bacterium Bacteroides thetaiotaomicron and the methanogenic archaeon Methanobrevibacter smithii, are proposed to have a synergistic metabolic relationship. Both organisms play vital roles in human gut health; B. thetaiotaomicron assists the host by fermenting dietary polysaccharides, whereas M. smithii consumes end-stage fermentation products and is hypothesized to relieve feedback inhibition of upstream microbes such as B. thetaiotaomicron. To study their metabolic interactions, we defined and optimized a coculture system and used software testing techniques to analyze growth under a range of conditions representing the nutrient environment of the host. We verify that B. thetaiotaomicron fermentation products are sufficient for M. smithii growth and that accumulation of fermentation products alters secretion of metabolites by B. thetaiotaomicron to benefit M. smithii. Studies suggest that B. thetaiotaomicron metabolic efficiency is greater in the absence of fermentation products or in the presence of M. smithii. Under certain conditions, B. thetaiotaomicron and M. smithii form interspecies granules consistent with behavior observed for syntrophic partnerships between microbes in soil or sediment enrichments and anaerobic digesters. Furthermore, when vitamin B12, hematin, and hydrogen gas are abundant, coculture growth is greater than the sum of growth observed for monocultures, suggesting that both organisms benefit from a synergistic mutual metabolic relationship. IMPORTANCE The human gut functions through a complex system of interactions between the host human tissue and the microbes which inhabit it. These diverse interactions are difficult to model or examine under controlled laboratory conditions. We studied the interactions between two dominant human gut microbes, B. thetaiotaomicron and M. smithii, using a seven-component culturing approach that allows the systematic examination of the metabolic complexity of this binary microbial system. By combining high-throughput methods with machine learning techniques, we were able to investigate the interactions between two dominant genera of the gut microbiome in a wide variety of environmental conditions. Our approach can be broadly applied to studying microbial interactions and may be extended to evaluate and curate computational metabolic models. The software tools developed for this study are available as user-friendly tutorials in the Department of Energy KBase.", "conclusion": "Our approach can be broadly applied to studying microbial interactions and may be extended to evaluate and curate computational metabolic models. The software tools developed for this study are available as user-friendly tutorials in the Department of Energy KBase." }, { "pmid": "35484138", "year": 2022, "title": "Magnesium galvanic cells produce hydrogen and modulate the tumor microenvironment to inhibit cancer growth.", "title_en": null, "title_de": "Magnesium-Galvanikzellen erzeugen Wasserstoff und modulieren die Tumormikroumgebung, um das Krebswachstum zu hemmen", "journal": "Nature communications", "authors": "Yang et al.", "author_search": "yang yang", "doi": "10.1038/s41467-022-29938-6", "doi_url": "https://doi.org/10.1038/s41467-022-29938-6", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/35484138/", "url": "https://h2medicine.org/studies/study-yang-2022-magnesium-galvanic-cells-produce/", "methods": [ "unspecified" ], "indications": [ "cancer", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2022 · Yang — Magnesium galvanic cells produce hydrogen and modulate the tumor microenvironment to inhibit cancer growth", "summary": "Researchers implanted a magnesium-platinum galvanic rod directly into tumors in animal models; the resulting continuous hydrogen production suppressed tumor growth by disrupting mitochondrial function and neutralizing the acidic tumor environment. The approach was tested in murine tumor models, patient-derived xenografts, and rabbit VX2 tumors — all preclinical. This is an animal study; results cannot be directly transferred to humans. (Nature Communications, 2022.)", "assessment": "An innovative animal study exploring implantable hydrogen delivery for oncology. The multi-model approach (mouse, PDX, rabbit) strengthens internal consistency, but all results are preclinical. Human translation requires safety studies, surgical feasibility work, and clinical trials that do not yet exist. The concept is promising as a research direction; it is not a ready therapy.", "abstract": "Hydrogen can be used as an anti-cancer treatment. However, the continuous generation of H2 molecules within the tumor is challenging. Magnesium (Mg) and its alloys have been extensively used in the clinic as implantable metals. Here we develop, by decorating platinum on the surface of Mg rods, a Mg-based galvanic cell (MgG), which allows the continuous generation of H2 in an aqueous environment due to galvanic-cell-accelerated water etching of Mg. By implanting MgG rods into a tumor, H2 molecules can be generated within the tumor, which induces mitochondrial dysfunction and intracellular redox homeostasis destruction. Meanwhile, the Mg(OH)2 residue can neutralize the acidic tumor microenvironment (TME). Such MgG rods with the micro-galvanic cell structure enable hydrogen therapy to inhibit the growth of tumors, including murine tumor models, patient-derived xenografts (PDX), as well as VX2 tumors in rabbits. Our research suggests that the galvanic cells for hydrogen therapy based on implantable metals may be a safe and effective cancer treatment.", "conclusion": "Such MgG rods with the micro-galvanic cell structure enable hydrogen therapy to inhibit the growth of tumors, including murine tumor models, patient-derived xenografts (PDX), as well as VX2 tumors in rabbits. Our research suggests that the galvanic cells for hydrogen therapy based on implantable metals may be a safe and effective cancer treatment." }, { "pmid": "35300173", "year": 2022, "title": "Local Treatment of Hydrogen-Rich Saline Promotes Wound Healing In Vivo by Inhibiting Oxidative Stress via Nrf-2/HO-1 Pathway.", "title_en": null, "title_de": "Die lokale Behandlung mit wasserstoffreicher Kochsalzlösung fördert die Wundheilung in vivo durch Hemmung des oxidativen Stresses über den Nrf-2/HO-1-Signalweg", "journal": "Oxidative medicine and cellular longevity", "authors": "Li et al.", "author_search": "li li", "doi": "10.1155/2022/2949824", "doi_url": "https://doi.org/10.1155/2022/2949824", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/35300173/", "url": "https://h2medicine.org/studies/study-li-2022-local-saline-promotes-wound/", "methods": [ "saline-iv" ], "indications": [ "metabolic", "cancer", "skin-aging", "immune-system", "oxidative-stress", "fundamentals-safety" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2022 · Li — Local Treatment of Hydrogen-Rich Saline Promotes Wound Healing In Vivo by Inhibiting Oxidative Stress via Nrf-2/HO-1 Pathway", "summary": "Applying hydrogen-rich saline directly to skin wounds in mice accelerated wound closure and reduced inflammation compared to regular saline, with the Nrf-2/HO-1 antioxidant pathway identified as the key mechanism. Additional cell-culture experiments confirmed that hydrogen-rich medium reduces oxidative stress in human epidermal cells. This is an animal and cell study; results cannot be directly transferred to humans. (Oxidative Medicine and Cellular Longevity, 2022.)", "assessment": "A well-designed animal and in-vitro study with a plausible mechanistic pathway (Nrf-2/HO-1). Local hydrogen application is a less-studied delivery route compared to inhalation or drinking, making this methodologically interesting. However, all results are preclinical: mice and cultured human cells are not substitutes for controlled human wound-healing trials. The effect size and optimal dosing for humans remain unknown.", "abstract": "Wound healing is a complex dynamic process involving a large number of biological events. Excessive oxidative stress is a key factor delaying wound healing. Hydrogen is an antioxidant, anti-inflammatory, and antiapoptotic medical gas with safety, effectiveness, and penetrability. However, the effects of local treatment of hydrogen on wound healing and its potential mechanisms remain unclear. In this study, Kunming (KM) mice were used to set up a wound model. All the mice were randomly divided into the control, the local treatment with saline group, the local treatment with the hydrogen-rich saline group, and the intraperitoneal injection of the hydrogen-rich saline group. To evaluate the impact of hydrogen-rich saline on wound healing, we assessed the wound healing rate, wound closure time, histomorphology, oxidative stress indicators, inflammatory cytokines, the apoptosis index, and the expression of the nuclear factor-erythroid-related factor 2(Nrf-2). Furthermore, the immortalized nontumorigenic human epidermal (HaCaT) cells were chosen to investigate the therapeutic effects of hydrogen-rich medium on oxidative stress and its underlying mechanisms. The results showed that local treatment of hydrogen-rich saline shortened wound closure time and reduced the level of proinflammatory cytokines and lipid peroxidation. Meanwhile, it decreased the cell apoptosis index and increased the Nrf-2 expression. Besides, hydrogen-rich medium relieved the oxidative stress via the activation of the Nrf-2/heme oxygenase-1 (HO-1) pathway. In conclusion, local treatment of hydrogen-rich saline exhibits the healing-promoting function through antioxidant, anti-inflammatory, and antiapoptotic effects. Hydrogen relieves the oxidative stress in the wound microenvironment via Nrf-2/HO-1 signaling pathway. This study may offer a new strategy to promote wound healing and a new perspective to illustrate the mechanism of wound healing.", "conclusion": "Hydrogen relieves the oxidative stress in the wound microenvironment via Nrf-2/HO-1 signaling pathway. This study may offer a new strategy to promote wound healing and a new perspective to illustrate the mechanism of wound healing." }, { "pmid": "35273249", "year": 2022, "title": "Long-term and daily use of molecular hydrogen induces reprogramming of liver metabolism in rats by modulating NADP/NADPH redox pathways.", "title_en": null, "title_de": "Die langfristige und tägliche Anwendung von molekularem Wasserstoff induziert eine Reprogrammierung des Leberstoffwechsels bei Ratten durch Modulation der NADP/NADPH-Redox-Signalwege", "journal": "Scientific reports", "authors": "Adzavon et al.", "author_search": "adzavon adzavon", "doi": "10.1038/s41598-022-07710-6", "doi_url": "https://doi.org/10.1038/s41598-022-07710-6", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/35273249/", "url": "https://h2medicine.org/studies/study-adzavon-2022-long-term-daily-use/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "metabolic", "liver", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2022 · Adzavon — Long-term and daily use of molecular hydrogen induces reprogramming of liver metabolism in rats by modulating NADP/NADPH redox pathways", "summary": "Rats exposed to molecular hydrogen for six months — either by drinking hydrogen-rich water or inhaling 4 % H₂ gas — showed reduced fat accumulation in the liver, lower blood lipid levels, and broad metabolic changes driven by the NADP/NADPH redox system. This is the first study to combine transcriptomics and metabolomics to map the molecular targets of long-term H₂ exposure. This is an animal study; no human data are available. (Scientific Reports, 2022.)", "assessment": "A first-of-its-kind mechanistic animal study providing multi-omics evidence for long-term H₂ effects on liver metabolism. The dual-route design (inhalation vs. HRW) and six-month duration make it methodologically stronger than typical short-term rodent studies. However, this is purely preclinical research in healthy rats. The NADP/NADPH findings are mechanistic hypothesis-generators — not proof that H₂ improves liver disease outcomes in humans. Translation to human metabolic or liver disease remains to be demonstrated.", "abstract": "Molecular hydrogen (H2) has emerged as a new therapeutic option in several diseases and is widely adopted by healthy people. However, molecular data to support therapeutic functions attributed to the biological activities of H2 remain elusive. Here, using transcriptomic and metabolomic approaches coupled with biochemistry and micro-CT technics, we evaluated the effect of long-term (6 months) and daily use of H2 on liver function. Rats exposed 2 h daily to H2 either by drinking HRW (H2 dissolved in H2O) or by breathing 4% H2 gas showed reduced lipogenesis and enhanced lipolysis in the liver, which was associated with apparent loss of visceral fat and brown adipose tissue together with a reduced level of serum lipids. Both transcripts and metabolites enriched in H2-treated rats revealed alteration of amino acid metabolism pathways and activation of purine nucleotides and carbohydrate biosynthesis pathways. Analysis of the interaction network of genes and metabolites and correlation tests revealed that NADP is the central regulator of H2 induced metabolic alterations in the liver, which was further confirmed by an increase in the level of components of metabolic pathways that require NADP as substrate. Evidence of immune response regulation activity was also observed in response to exposure to H2. This work is the first to provide metabolomic and transcriptomic data to uncover molecular targets for the effect of prolonged molecular hydrogen treatment on liver metabolism.", "conclusion": "Evidence of immune response regulation activity was also observed in response to exposure to H2. This work is the first to provide metabolomic and transcriptomic data to uncover molecular targets for the effect of prolonged molecular hydrogen treatment on liver metabolism." }, { "pmid": "35258003", "year": 2022, "title": "Hydrogen-rich water can reduce the formation of biogenic amines in butter.", "title_en": null, "title_de": "Wasserstoffreiches Wasser kann die Bildung biogener Amine in Butter reduzieren", "journal": "Food chemistry", "authors": "Bulut et al.", "author_search": "bulut bulut", "doi": "10.1016/j.foodchem.2022.132613", "doi_url": "https://doi.org/10.1016/j.foodchem.2022.132613", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/35258003/", "url": "https://h2medicine.org/studies/study-bulut-2022-can-reduce-formation-biogenic/", "methods": [ "drinking-hrw" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2022 · Bulut — Hydrogen-rich water can reduce the formation of biogenic amines in butter", "summary": "Washing raw butter with hydrogen-rich water — prepared either by bubbling hydrogen gas or by adding magnesium — significantly reduced the formation of biogenic amines (including histamine, tryptamine, and spermidine) during 90 days of storage. This is a food-chemistry in-vitro study; it tests H₂ as a food-safety tool, not as a health intervention in humans. (Food Chemistry, 2022.)", "assessment": "This is a food-chemistry in-vitro study, not a clinical or animal experiment. Its relevance is to food safety and food technology, not to hydrogen-medicine endpoints. No human health outcomes are tested. The findings are technically interesting and potentially applicable in dairy production, but they do not speak to any therapeutic use of molecular hydrogen in the body.", "abstract": "The formation of biogenic amines in food products forms a serious challenge for food producers and a hazard for consumers. Butter was washed by hydrogen-rich water (HRW) prepared using two methods, i.e. hydrogen-bubbled water (H2 water) and magnesium-incorporated water (Mg water). After 90 days of storage, the lowest formation levels of biogenic amines were shown for butter samples washed with HRW (H2 water and Mg water), while the highest levels were identified for the butter samples washed with normal water. Washing raw butter with HRW led to a significant decrease in tryptamine, 2-phenylethylamine, spermidine, and spermine formation. The lowest histamine level was shown for butter samples washed with H2 and Mg, while the highest level was found for butter washed with normal water. Washing butter with HRW revealed no inhibiting effect on yogurt bacteria during storage. The proposed method involves molecular hydrogen which is non-toxic for humans and the environment.", "conclusion": "Washing butter with HRW revealed no inhibiting effect on yogurt bacteria during storage. The proposed method involves molecular hydrogen which is non-toxic for humans and the environment." }, { "pmid": "35187885", "year": 2022, "title": "Molecular hydrogen is a promising therapeutic agent for pulmonary disease.", "title_en": null, "title_de": "Molekularer Wasserstoff ist ein vielversprechendes Therapeutikum für Lungenerkrankungen", "journal": "Journal of Zhejiang University. Science. B", "authors": "Fu et al.", "author_search": "fu fu", "doi": "10.1631/jzus.b2100420", "doi_url": "https://doi.org/10.1631/jzus.b2100420", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/35187885/", "url": "https://h2medicine.org/studies/study-fu-2022-promising-therapeutic-agent-pulmonary/", "methods": [ "unspecified" ], "indications": [ "cardiovascular", "cancer", "respiratory", "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2022 · Fu — Molecular hydrogen is a promising therapeutic agent for pulmonary disease", "summary": "This review summarizes the growing body of evidence suggesting that molecular hydrogen can protect the lungs from a range of diseases — including acute lung injury, COPD, asthma, lung cancer, pulmonary hypertension, and pulmonary fibrosis — through its antioxidant, anti-inflammatory, and anti-apoptotic properties. As a review, this paper synthesizes existing research rather than reporting new experiments. The authors describe mechanisms and preclinical as well as some early clinical findings. (Journal of Zhejiang University Science B, 2022.)", "assessment": "A useful narrative review that maps the existing H₂ research landscape for lung diseases. Its value is as an orientation and reference document. As a review, it does not produce new experimental evidence. The strength of evidence differs considerably by disease: some areas (acute lung injury) are better supported; others (PAH, pulmonary fibrosis) remain at an early mechanistic stage. Readers should treat conclusions as a map of research directions, not as established clinical guidance.", "abstract": "Molecular hydrogen exerts biological effects on nearly all organs. It has anti-oxidative, anti-inflammatory, and anti-aging effects and contributes to the regulation of autophagy and cell death. As the primary organ for gas exchange, the lungs are constantly exposed to various harmful environmental irritants. Short- or long-term exposure to these harmful substances often results in lung injury, causing respiratory and lung diseases. Acute and chronic respiratory diseases have high rates of morbidity and mortality and have become a major public health concern worldwide. For example, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. An increasing number of studies have revealed that hydrogen may protect the lungs from diverse diseases, including acute lung injury, chronic obstructive pulmonary disease, asthma, lung cancer, pulmonary arterial hypertension, and pulmonary fibrosis. In this review, we highlight the multiple functions of hydrogen and the mechanisms underlying its protective effects in various lung diseases, with a focus on its roles in disease pathogenesis and clinical significance.", "conclusion": "An increasing number of studies have revealed that hydrogen may protect the lungs from diverse diseases, including acute lung injury, chronic obstructive pulmonary disease, asthma, lung cancer, pulmonary arterial hypertension, and pulmonary fibrosis. In this review, we highlight the multiple functions of hydrogen and the mechanisms underlying its protective effects in various lung diseases, with a" }, { "pmid": "35075943", "year": 2022, "title": "Quantification of dissolved H2 and continuous monitoring of hydrogen-rich water for haemodialysis applications: An experimental study.", "title_en": null, "title_de": "Quantifizierung von gelöstem H₂ und kontinuierliche Überwachung von wasserstoffreichem Wasser für Hämodialyseanwendungen: Eine experimentelle Studie", "journal": "The International journal of artificial organs", "authors": "Mouzakis et al.", "author_search": "mouzakis mouzakis", "doi": "10.1177/03913988211070588", "doi_url": "https://doi.org/10.1177/03913988211070588", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/35075943/", "url": "https://h2medicine.org/studies/study-mouzakis-2022-quantification-dissolved-continuous-monitoring/", "methods": [ "drinking-hrw" ], "indications": [ "kidney-dialysis", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2022 · Mouzakis — Quantification of dissolved H₂ and continuous monitoring of hydrogen-rich water for haemodialysis applications: An experimental study", "summary": "This study validated a contactless electrochemical sensor for continuously measuring dissolved hydrogen concentrations in physiological solutions relevant to haemodialysis. The sensor showed a linear relationship between applied H₂ content and equilibrium concentration, though calibration differences between sensors and temperature sensitivity require attention. This is an in-vitro instrumentation study — no patients or animals were involved. (The International Journal of Artificial Organs, 2022.)", "assessment": "A technical in-vitro validation study for H₂ measurement instrumentation in a dialysis-relevant context. This is engineering groundwork, not a clinical or biological study. No patient outcomes are assessed. The findings support the feasibility of real-time H₂ monitoring in haemodialysis circuits, which is a prerequisite for safe clinical use — but the clinical benefits of H₂-enriched dialysate themselves must be evaluated separately.", "abstract": "The prevalence of oxidative and inflammatory stress in end-stage renal disease (ESRD) patients has often been associated with chronic haemodialysis therapies. Over the past decades, several reports have shown the potential of hydrogen molecule as an antioxidant in the treatment of various medical conditions in animal models, as well as in pilot studies with human patients. Recently, a hydrogen-enriched dialysate solution has been introduced, holding promise in reducing the oxidative and/or inflammatory complications arising during haemodialysis. To this end, a standardised measuring method to determine the levels of hydrogen in dialysate and subsequently in blood is required. This study explores the possibility of quantifying hydrogen concentration using a novel contactless sensor that detects dissolved hydrogen in liquids. An experimental circuit is assembled to validate the sensitivity and accuracy of the hydrogen monitoring system (Pureron Japan Co., Ltd) through in vitro investigations with physiological solutions. Measurements of dissolved molecular hydrogen concentration are corroborated by an established oxygen sensor providing continuous partial pressure readings. The relationship between the applied H2 content in the gaseous mixture and the H2 concentration value at equilibrium is linear. At the same time, the hydrogen monitoring system has a rather long response time, and its readings seem to slightly diverge from sensor to sensor as well as at different temperatures. For this reason, a sensor recalibration might be necessary, which could become part of the product's ongoing development. Nevertheless, the aforementioned minor deficiencies can be mostly considered negligible in applications such as haemodialysis.", "conclusion": "For this reason, a sensor recalibration might be necessary, which could become part of the product's ongoing development. Nevertheless, the aforementioned minor deficiencies can be mostly considered negligible in applications such as haemodialysis." }, { "pmid": "35025709", "year": 2022, "title": "Microbial hydrogen economy alleviates colitis by reprogramming colonocyte metabolism and reinforcing intestinal barrier.", "title_en": null, "title_de": "Die mikrobielle Wasserstoffökonomie lindert Kolitis durch Reprogrammierung des Kolonozytenstoffwechsels und Stärkung der Darmbarriere", "journal": "Gut microbes", "authors": "Ge et al.", "author_search": "ge ge", "doi": "10.1080/19490976.2021.2013764", "doi_url": "https://doi.org/10.1080/19490976.2021.2013764", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/35025709/", "url": "https://h2medicine.org/studies/study-ge-2022-microbial-economy-alleviates-colitis/", "methods": [ "inhalation", "saline-iv" ], "indications": [ "metabolic", "sports-exercise", "immune-system", "oxidative-stress", "fundamentals-safety" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2022 · Ge — Microbial hydrogen economy alleviates colitis by reprogramming colonocyte metabolism and reinforcing intestinal barrier", "summary": "In mice with experimentally induced acute colitis, hydrogen-rich saline administration reduced intestinal inflammation, increased beneficial short-chain fatty acid (SCFA)-producing bacteria, and strengthened the gut barrier. The proposed mechanism centers on the H₂–gut microbiota–SCFA axis and modulation of specific bacteria that degrade the protective mucus layer. This is an animal study; results cannot be directly transferred to humans. (Gut Microbes, 2022.)", "assessment": "A mechanistically rich preclinical animal study that provides a multi-pathway explanation for H₂'s anti-colitis effects. The DSS model is widely used but does not fully replicate human IBD. All results are from mice, and direct human relevance requires clinical confirmation. The microbiota–SCFA–PPARγ axis is a compelling and scientifically plausible pathway, making this paper a useful reference for hypothesis-building. The two delivery routes (inhalation and intraperitoneal saline injection) also help distinguish H₂-specific effects from saline effects.", "abstract": "With the rapid development and high therapeutic efficiency and biosafety of gas-involving theranostics, hydrogen medicine has been particularly outstanding because hydrogen gas (H2), a microbial-derived gas, has potent anti-oxidative, anti-apoptotic, and anti-inflammatory activities in many disease models. Studies have suggested that H2-enriched saline/water alleviates colitis in murine models; however, the underlying mechanism remains poorly understood. Despite evidence demonstrating the importance of the microbial hydrogen economy, which reflects the balance between H2-producing (hydrogenogenic) and H2-utilizing (hydrogenotrophic) microbes in maintaining colonic mucosal ecosystems, minimal efforts have been exerted to manipulate relevant H2-microbe interactions for colonic health. Consistent with previous studies, we found that administration of hydrogen-rich saline (HS) ameliorated dextran sulfate sodium-induced acute colitis in a mouse model. Furthermore, we demonstrated that HS administration can increase the abundance of intestinal-specific short-chain fatty acid (SCFA)-producing bacteria and SCFA production, thereby activating the intracellular butyrate sensor peroxisome proliferator-activated receptor γ signaling and decreasing the epithelial expression of Nos2, consequently promoting the recovery of the colonic anaerobic environment. Our results also indicated that HS administration ameliorated disrupted intestinal barrier functions by modulating specific mucosa-associated mucolytic bacteria, leading to substantial inhibition of opportunistic pathogenic Escherichia coli expansion as well as a significant increase in the expression of interepithelial tight junction proteins and a decrease in intestinal barrier permeability in mice with colitis. Exogenous H2 reprograms colonocyte metabolism by regulating the H2-gut microbiota-SCFAs axis and strengthens the intestinal barrier by modulating specific mucosa-associated mucolytic bacteria, wherein improved microbial hydrogen economy alleviates colitis.", "conclusion": "Our results also indicated that HS administration ameliorated disrupted intestinal barrier functions by modulating specific mucosa-associated mucolytic bacteria, leading to substantial inhibition of opportunistic pathogenic Escherichia coli expansion as well as a significant increase in the expression of interepithelial tight junction proteins and a decrease in intestinal barrier permeability in m" }, { "pmid": "34995727", "year": 2022, "title": "Gender-based differences in neuroprotective effects of hydrogen gas against intracerebral hemorrhage-induced depression.", "title_en": null, "title_de": "Geschlechtsspezifische Unterschiede in den neuroprotektiven Wirkungen von Wasserstoffgas gegen durch intrazerebrale Blutung induzierte Depression", "journal": "Neurochemistry international", "authors": "An et al.", "author_search": "an an", "doi": "10.1016/j.neuint.2022.105276", "doi_url": "https://doi.org/10.1016/j.neuint.2022.105276", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/34995727/", "url": "https://h2medicine.org/studies/study-an-2022-gender-differences-neuroprotective-against/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "sports-exercise", "neurology", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2022 · An — Gender-based differences in neuroprotective effects of hydrogen gas against intracerebral hemorrhage-induced depression", "summary": "In a mouse model of intracerebral hemorrhage (ICH), hydrogen gas inhalation provided stronger neuroprotective effects against post-stroke depression in female mice than in males — and adding estrogen to male mice restored comparable H₂ efficacy. The study identifies estrogen-mediated suppression of NF-κB signaling in astrocytes as the likely explanation. This is an animal study; results cannot be directly transferred to humans. (Neurochemistry International, 2022.)", "assessment": "A preclinical animal study highlighting an important but under-researched dimension of H₂ research: sex-based differences in response. The finding that estrogen modulates H₂ efficacy is scientifically interesting and has potential implications for designing human trials (e.g., whether H₂ interventions should stratify by sex or hormonal status). However, all results are from mice, and the specific model (post-ICH depression) limits direct generalization even within the preclinical field.", "abstract": "BACKGROUND: Post-stroke depression (PSD) severely affects recovery in patients with intracerebral hemorrhage (ICH). Although hydrogen gas (H2) exerts excellent neuroprotective effects in patients with ICH, there are sex-based differences in H2 efficacy in several diseases. Herein, we determined whether estrogen increases susceptibility to the neuroprotective effects of H2 in males with ICH-induced depression. METHODS: A rodent model of ICH in the basal ganglia was established using autologous blood injection (30 μL). Mice were treated with 2.9% H2 for 2 h daily for 3 days post-ICH. Estrogen (1 mg/kg) was administered by subcutaneous injection daily for 3 days to male mice post-ICH. Thirty days post-ICH, PSD was evaluated by sucrose preference, forced swimming, and 3-chamber social tests. Following the completion of behavioral tests, levels of superoxide dismutase (SOD) and reactive oxygen species (ROS), astrocytic activation, phosphorylated (p)-NF-κB-positive astrocytes, p-NF-κB, p-IKKβ, IL-1β, and IL-6 expression were determined. RESULTS: Compared with female mice, H2 administration post-ICH exhibited fewer neuroprotective effects, including decreased sucrose consumption and time spent sniffing a novel mouse, increased immobility time, downregulated total SOD content, upregulated ROS content and p-NF-κB levels, and elevated astrocyte branches, whereas estrogen enhanced the neuroprotective effects of H2 in male mice. A reduced number of p-NF-κB-positive astrocytes, downregulated expression of p-NF-κB, p-IKKβ, IL-1β, and IL-6 in the amygdala were demonstrated in ICH-males treated with estrogen plus H2. CONCLUSIONS: Estrogen was responsible for increased H2 sensitivity in male mice with ICH. The underlying mechanism may be associated with the suppression of NF-κB signaling in astrocytes.", "conclusion": "Estrogen was responsible for increased H2 sensitivity in male mice with ICH. The underlying mechanism may be associated with the suppression of NF-κB signaling in astrocytes." }, { "pmid": "34854421", "year": 2022, "title": "In vivo microelectrode monitoring of real-time hydrogen concentration in different tissues of rats after inhaling hydrogen gas.", "title_en": null, "title_de": "In-vivo-Mikroelektroden-Überwachung der Echtzeit-Wasserstoffkonzentration in verschiedenen Geweben von Ratten nach Inhalation von Wasserstoffgas", "journal": "Medical gas research", "authors": "Liu et al.", "author_search": "liu liu", "doi": "10.4103/2045-9912.330694", "doi_url": "https://doi.org/10.4103/2045-9912.330694", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/34854421/", "url": "https://h2medicine.org/studies/study-liu-2022-vivo-microelectrode-monitoring-real/", "methods": [ "inhalation" ], "indications": [ "metabolic", "liver", "sports-exercise", "neurology", "kidney-dialysis" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2022 · Liu — In vivo microelectrode monitoring of real-time hydrogen concentration in different tissues of rats after inhaling hydrogen gas", "summary": "Using implanted electrochemical microelectrodes, researchers measured hydrogen concentrations in seven different rat tissues in real time during and after inhalation of 4 %, 42 %, and 67 % H₂ gas. Brain tissue reached the highest H₂ equilibrium concentrations; muscle and adipose tissue accumulated and cleared H₂ more slowly. Tissue concentrations scaled proportionally with inhaled dose. This is an animal study providing pharmacokinetic baseline data for hydrogen research. (Medical Gas Research, 2022.)", "assessment": "A technically valuable preclinical pharmacokinetic study filling a genuine gap in hydrogen dose-response data. Real-time in-vivo monitoring of seven tissues simultaneously is methodologically novel. The findings have direct relevance for experimental design in H₂ research. However, this is an animal study in rats; tissue distribution kinetics may differ in humans due to differences in body composition, cardiac output, and tissue perfusion rates. No therapeutic endpoints are measured.", "abstract": "Medical effects of hydrogen have been reported in many studies. Due to difficulties in measuring hydrogen concentration in vivo after intake and high explosive risks of hydrogen, studies about dose-response relationships and tissue concentrations of hydrogen are few. Here, for the first time, we monitored real-time hydrogen concentrations in different tissues in rats including brain, liver, spleen, kidney, thigh muscle, inguinal white adipose tissue, and gonadal white adipose tissue after inhaling different concentrations of hydrogen (4%, 42%, and 67%) using an electrochemical sensor. Hydrogen concentrations in the same tissue showed a dose-dependent response. The equilibrium concentration values were highest in the brain and lowest in the thigh muscle. The saturation and desaturation curves changed more slowly in the thigh muscle and white adipose tissues than in other tissues. These results provide fundamental information for the selection of hydrogen dose applications in basic research and clinical trials. The experiments were approved by the Laboratory Animal Ethics Committee of Shandong First Medical University & Shandong Academy of Medical Sciences (No. 2020-1028) on March 18, 2020.", "conclusion": "The experiments were approved by the Laboratory Animal Ethics Committee of Shandong First Medical University & Shandong Academy of Medical Sciences (No. 2020-1028) on March 18, 2020." }, { "pmid": "34854419", "year": 2022, "title": "Hydrogen-rich bath with nano-sized bubbles improves antioxidant capacity based on oxygen radical absorbing and inflammation levels in human serum.", "title_en": null, "title_de": "Wasserstoffreiches Bad mit nanogroßen Bläschen verbessert die antioxidative Kapazität und die Entzündungswerte im menschlichen Serum", "journal": "Medical gas research", "authors": "Tanaka et al.", "author_search": "tanaka tanaka", "doi": "10.4103/2045-9912.330692", "doi_url": "https://doi.org/10.4103/2045-9912.330692", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/34854419/", "url": "https://h2medicine.org/studies/study-tanaka-2022-bath-nano-sized-bubbles/", "methods": [ "bath-topical" ], "indications": [ "skin-aging", "immune-system", "oxidative-stress", "fundamentals-safety" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2022 · Tanaka — Hydrogen-rich bath with nano-sized bubbles improves antioxidant capacity and inflammation levels in human serum", "summary": "A 10-minute bath in hydrogen-rich water with nano-bubbles raised blood antioxidant capacity by about 11% and lowered the inflammatory marker CRP by roughly 30% in healthy volunteers — and sustained CRP reductions were observed in patients with autoimmune conditions over months of daily bathing. The nano-bubble delivery system achieved substantially higher dissolved H₂ than conventional methods. (Medical Gas Research, 2022.)", "assessment": "An interesting proof-of-concept study with a novel delivery method (nano-bubbles). The healthy-volunteer data are internally controlled and the H₂ specificity is supported by the active vs. plain water comparison. Limitations: the patient subgroups are small (6 and several unspecified patients), unrandomised, and unblinded; the 2–25 month follow-up data are observational with no control arm; CRP is a non-specific marker; the ethics approval was from a non-governmental anti-aging organisation (not a hospital IRB), which limits institutional credibility. The nano-bubble approach itself is a promising delivery innovation worth exploring in rigorous trials.", "abstract": "This study compared the effects of hydrogen-water (HW) bath on the oxygen radical absorption-based antioxidant capacity and the inflammatory indicator, C-reactive protein (CRP), in serum between healthy volunteers and inflammatory/collagen disease-patients. The HW bath apparatus supplied nano-bubbles with a diameter of 110 ± 10 nm and 338-682 μg/L of dissolved hydrogen after 120 minutes electrolysis, and nano-bubbles increased to 9.91 × 107/mL along with the increase of correlative dissolved hydrogen. Ten-minute HW bath increased the oxygen radical absorption-based antioxidant capacity to 110.9 ± 9.2% at post-bathing 120 minutes, although unaltered with 10-minute normal water bath at 40°C in healthy subjects. The CRP level was repressed to 70.2 ± 12.1% at 120 minutes after HW bath, although rather increased for normal water bath. In the patients with connective tissue diseases, the CRP level was repressed to 3-24% upon 9 days to 4 months of HW bathing. In another six patients with diverse autoimmune-related diseases, upon daily HW bathing as long as 2-25 months, the pre-bathing CRP level of 5.31 mg/dL decreased to 0.24 mg/dL being within the standard-range, with relief of visible inflammatory symptoms for some cases. Thus, the HW bath with high-density nano-bubbles has beneficial effects on serum antioxidant capacity, inflammation, and the skin appearance. The study was approved by the Committee of Ethics, Japanese Center of Anti-Aging Medical Sciences (Authorization No. H-15-03-2, on January 15, 2019), which was a non-profitable organization officially authenticated by the Hiroshima Prefecture Government of Japan.", "conclusion": "The study was approved by the Committee of Ethics, Japanese Center of Anti-Aging Medical Sciences (Authorization No. H-15-03-2, on January 15, 2019), which was a non-profitable organization officially authenticated by the Hiroshima Prefecture Government of Japan." }, { "pmid": "34655499", "year": 2022, "title": "Metal-Organic-Framework-Based Hydrogen-Release Platform for Multieffective Helicobacter Pylori Targeting Therapy and Intestinal Flora Protective Capabilities.", "title_en": null, "title_de": "Metallorganische-Gerüstverbindungs-basierte Wasserstofffreisetzungsplattform für eine multieffektive zielgerichtete Helicobacter-pylori-Therapie und intestinale-Flora-schützende Fähigkeiten", "journal": "Advanced materials (Deerfield Beach, Fla.)", "authors": "Zhang et al.", "author_search": "zhang zhang", "doi": "10.1002/adma.202105738", "doi_url": "https://doi.org/10.1002/adma.202105738", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/34655499/", "url": "https://h2medicine.org/studies/study-zhang-2022-metal-organic-framework-release/", "methods": [ "unspecified" ], "indications": [ "cancer", "immune-system" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2022 · Zhang — Metal-Organic-Framework-Based Hydrogen-Release Platform for Multieffective Helicobacter Pylori Targeting Therapy and Intestinal Flora Protective Capabilities", "summary": "Researchers developed a pH-responsive nanoparticle system (palladium-hydrogen loaded into a zinc-based metal-organic framework, coated with an anti-inflammatory hydrogel) that, in both cell and animal experiments, selectively targets stomach inflammation sites, releases hydrogen to kill H. pylori, reduces inflammation, and protects the intestinal microbiome. This is an in-vitro and animal study; no clinical human data exist. (Advanced Materials, 2022.)", "assessment": "A sophisticated in-vitro and animal proof-of-concept study for nanoparticle-mediated targeted H₂ delivery against H. pylori. The multi-mechanism design (targeted delivery + antimicrobial Zn²⁺ + H₂ anti-inflammation + microbiome protection) is scientifically creative. However, this is entirely preclinical research. The safety, pharmacokinetics, manufacturability, and regulatory pathway for such a complex nanoparticle system in humans are entirely untested. The findings are a compelling research direction, not a clinical application.", "abstract": "Helicobacter pylori (H. pylori) infection is the leading cause of chronic gastritis, peptic ulcer, and gastric cancer. Antibiotics, as traditional method for eliminating H. pylori, have no targeting effect, which causes serious bacterial resistance and gut dysbacteriosis. Moreover, antibiotics can hardly address hyperactive inflammatory response or damaged gastric mucosal barrier caused by H. pylori infection. Here, a pH-responsive metal-organic framework hydrogen-generation nanoparticle (Pd(H) @ ZIF-8) is reported, which is encapsulated with ascorbate palmitate (AP) hydrogel. Both in vitro and in vivo experiments demonstrate that the outer AP hydrogel can target and adhere to the inflammatory site through electrostatic interactions, and is then hydrolyzed by matrix metalloproteinase (MMP) enriching in inflammatory sites. The released Pd(H) @ ZIF-8 nanoparticles are further decomposed by gastric acid to generate zinc ions (Zn2+ ) and hydrogen, thus effectively killing H. pylori, alleviating inflammation and restoring impaired gastric mucosa simultaneously. Unexpectedly, this metal-organic framework hydrogen-generation platform (Pd(H) @ ZIF-8 @ AP) also has an effect toward avoiding the imbalance of intestinal flora, which thus provides a more precise, effective, and healthy strategy for the treatment of H. pylori infection.", "conclusion": "Unexpectedly, this metal-organic framework hydrogen-generation platform (Pd(H) @ ZIF-8 @ AP) also has an effect toward avoiding the imbalance of intestinal flora, which thus provides a more precise, effective, and healthy strategy for the treatment of H. pylori infection." }, { "pmid": "34583156", "year": 2022, "title": "Regulation of chlorothalonil degradation by molecular hydrogen.", "title_en": null, "title_de": "Regulation des Chlorothalonil-Abbaus durch molekularen Wasserstoff", "journal": "Journal of hazardous materials", "authors": "Wang et al.", "author_search": "wang wang", "doi": "10.1016/j.jhazmat.2021.127291", "doi_url": "https://doi.org/10.1016/j.jhazmat.2021.127291", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/34583156/", "url": "https://h2medicine.org/studies/study-wang-2022-regulation-chlorothalonil-degradation/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2022 · Wang — Regulation of chlorothalonil degradation by molecular hydrogen", "summary": "This in-vitro and plant study shows that molecular hydrogen accelerates the breakdown of the fungicide chlorothalonil in several crop plants — including tomato, rice, and cabbage — without reducing the pesticide's antifungal effectiveness. The mechanism involves H₂-stimulated brassinosteroid hormones that upregulate detoxification enzymes. This is a plant biology study with no direct relevance to human health therapy. (Journal of Hazardous Materials, 2022.)", "assessment": "This is a plant biology and agricultural chemistry study — not a hydrogen-medicine or human health study. Its relevance is to sustainable agriculture and pesticide safety in the food chain. No human health endpoints are assessed. The scientific contribution lies in identifying H₂ as a potential tool to reduce pesticide residues in crops without compromising fungicidal protection, which is a valid and interesting applied finding.", "abstract": "Pesticides can accumulate throughout the food chain to potentially endanger human health. Although molecular hydrogen (H2) is widely used in industry and medicine, its application in agriculture is just beginning. This study showed that H2 enhances the degradation of the fungicide chlorothalonil (CHT) in plants, but does not reduce its antifungal efficacy. Pharmacological evidence confirmed the contribution of H2-stimulated brassinosteroids (BRs) in the above responses. The genetic increased endogenous H2 with overexpression of hydrogenase 1 gene (CrHYD1) from Chlamydomonas reinhardtii in Arabidopsis not only increased BRs levels, but also eventually intensified the degradation of CHT. Expression of genes encoding some enzymes responsible for detoxification in tomato and Arabidopsis were also stimulated. Contrasting responses were observed after the pharmacological removal of endogenous BR. We further proved that H2 control of CHT degradation was relatively universal, with at least since its degradation in Chinese cabbage, cucumber, radish, alfalfa, rice, and rapeseed were differentially enhanced by H2. Collectively, above results clearly indicated that both exogenously and endogenously applied with H2 could stimulate degradation of CHT partially via BR-dependent detoxification. These results may open a new window for environmental-friendly hydrogen-based agriculture.", "conclusion": "Collectively, above results clearly indicated that both exogenously and endogenously applied with H2 could stimulate degradation of CHT partially via BR-dependent detoxification. These results may open a new window for environmental-friendly hydrogen-based agriculture." }, { "pmid": "34533646", "year": 2022, "title": "Molecular hydrogen suppresses Porphyromonas gingivalis lipopolysaccharide-induced increases in interleukin-1 alpha and interleukin-6 secretion in human gingival cells.", "title_en": null, "title_de": "Molekularer Wasserstoff unterdrückt die durch Porphyromonas-gingivalis-Lipopolysaccharid induzierte Erhöhung der Interleukin-1-alpha- und Interleukin-6-Sekretion in menschlichen Zahnfleischzellen.", "journal": "Molecular and cellular biochemistry", "authors": "Saitoh et al.", "author_search": "saitoh saitoh", "doi": "10.1007/s11010-021-04262-7", "doi_url": "https://doi.org/10.1007/s11010-021-04262-7", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/34533646/", "url": "https://h2medicine.org/studies/study-saitoh-2022-suppresses-porphyromonas-gingivalis-lipopolysaccharide/", "methods": [ "unspecified" ], "indications": [ "immune-system", "oral-health", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2022 · Saitoh — Molecular hydrogen suppresses Porphyromonas gingivalis lipopolysaccharide-induced increases in interleukin-1 alpha and interleukin-6 secretion in human gingival cells.", "summary": "In a laboratory cell model of periodontitis, molecular hydrogen (H₂) significantly reduced the secretion of two key inflammatory cytokines — IL-1α and IL-6 — triggered by a major periodontal pathogen. The effect was achieved without harming the cells themselves. This is a cell-culture study; no clinical conclusions about humans with periodontitis can be drawn from it. (Molecular and Cellular Biochemistry, 2022.)", "assessment": "An interesting in-vitro pilot signal for H₂ in the context of oral inflammation. This is a cell-culture study (in vitro), not a human trial — results are exploratory and cannot be directly transferred to clinical practice. Only two of eight cytokines were significantly affected; the breadth of the anti-inflammatory effect remains limited in this model. The study is a useful first step that motivates further research, but has no direct therapeutic implications for patients with periodontitis at this stage.", "abstract": "Periodontitis is defined as a multifactorial polymicrobial infection accompanied by inflammatory reactions. Porphyromonas gingivalis (Pg) is known as a major pathogen in the initiation and progression of periodontitis, and a major virulence factor is Pg lipopolysaccharide (LPS). Molecular hydrogen (H2) has been reported to act as a gaseous antioxidant, which suppresses periodontitis progression by decreasing gingival oxidative stress. However, no human periodontitis model has examined the anti-inflammatory effects of H2. In this study, we examined the effects of H2 on Pg LPS-induced secretion of 8 types of inflammation markers in a human periodontitis model using human gingival cells with enzyme-linked immunosorbent assays. Our results demonstrated that Pg LPS increased interleukin (IL) 1 alpha (IL-1α) and IL-6 secretion, but H2 significantly suppressed the secretion of both cytokines without cytotoxicity. H2 can suppress the production of IL-1α and IL-6, which are identified as cytokines involved in inflammatory reactions in periodontal disease. Thus, H2 may provide therapeutic applications for periodontitis.", "conclusion": "H2 can suppress the production of IL-1α and IL-6, which are identified as cytokines involved in inflammatory reactions in periodontal disease. Thus, H2 may provide therapeutic applications for periodontitis." }, { "pmid": "34365467", "year": 2022, "title": "Hydrogen-rich water reduced oxidative stress and renal fibrosis in rats with unilateral ureteral obstruction.", "title_en": null, "title_de": "Wasserstoffreiches Wasser reduzierte oxidativen Stress und renale Fibrose bei Ratten mit einseitiger Ureterobstruktion.", "journal": "Pediatric research", "authors": "Mizutani et al.", "author_search": "mizutani mizutani", "doi": "10.1038/s41390-021-01648-7", "doi_url": "https://doi.org/10.1038/s41390-021-01648-7", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/34365467/", "url": "https://h2medicine.org/studies/study-mizutani-2022-reduced-oxidative-stress-renal/", "methods": [ "drinking-hrw" ], "indications": [ "kidney-dialysis", "skin-aging", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2022 · Mizutani — Hydrogen-rich water reduced oxidative stress and renal fibrosis in rats with unilateral ureteral obstruction.", "summary": "In a rat model of obstructive kidney injury, drinking hydrogen-rich water (HRW) for two weeks after surgery significantly reduced interstitial fibrosis and oxidative stress markers in the affected kidney. The mechanism may involve the anti-aging protein klotho. This is an animal study; findings cannot be directly applied to humans. (Pediatric Research, 2022.)", "assessment": "This is an animal study (rats) and its results cannot be directly transferred to humans. The UUO model is a recognised experimental tool, but it represents an acute surgical obstruction, not the gradual development typical of congenital obstructive nephropathy in children. The involvement of klotho is an interesting mechanistic lead that merits further investigation. The finding that simple oral HRW intake was sufficient — without injections or invasive delivery — is notable for its translational relevance, but clinical proof is still lacking.", "abstract": "BACKGROUND: Congenital obstructive nephropathy (CKD) is commonly implicated in the pathophysiology of chronic kidney disease occurring in the pediatric and adolescent age groups and the release of reactive oxygen species contribute to the worsening of renal fibrosis. Molecular hydrogen (H2) protects against tissue injury by reducing oxidative stress. We evaluated the efficacy of oral H2-rich water (HW) intake in preventing unilateral ureteral obstruction (UUO)-induced renal injury in rats. METHODS: Male Sprague-Dawley UUO or control rats were administered with distilled water (DW) or HW for 2 weeks post-surgery. Histopathological and immunohistochemical analyses of kidney samples were performed. RESULTS: Histological changes were not apparent in the sham-operated kidneys. However, UUO kidneys were found to have widened interstitial spaces and tubular dilatation. Compared with the UUO + DW group, HW administration attenuated tubulointerstitial injury and reduced interstitial fibrotic area, causing a substantial decline in the frequency of α-SMA-, ED-1-, and TGF-β1-positive cells in the UUO + HW group. The decrease in the klotho mRNA expression in the UUO + HW group was less pronounced than that in the UUO + DW group. CONCLUSION: Oral HW intake reduced oxidative stress and prevented interstitial fibrosis in UUO kidneys, potentially involving klotho in the underlying mechanism. IMPACT: Oral intake of hydrogen-rich water (HW) can reduce oxidative stress and suppress interstitial fibrosis in unilateral ureteral obstruction-induced renal injury in rats. This mechanism possibly involves klotho, which is known for its antiaging roles. The association between molecular hydrogen and klotho in renal fibrosis is well known; this is the first report on the association in a unilateral ureteral obstruction model. Drinking HW is a safe and convenient treatment for oxidative stress-induced pathologies, without side effects. As a prospect for future research, oral HW intake to treat oxidative stress may improve renal fibrosis in congenital obstructive nephropathy.", "conclusion": "Oral HW intake reduced oxidative stress and prevented interstitial fibrosis in UUO kidneys, potentially involving klotho in the underlying mechanism." }, { "pmid": "36115583", "year": 2022, "title": "Molecular hydrogen has a positive impact on pregnancy maintenance through enhancement of mitochondrial function and immunomodulatory effects on T cells", "title_en": null, "title_de": "Molekularer Wasserstoff hat durch die Verbesserung der Mitochondrienfunktion und immunmodulatorische Effekte auf T-Zellen einen positiven Einfluss auf den Schwangerschaftserhalt", "journal": "Life Sciences", "authors": "Aoki et al.", "author_search": "aoki aoki", "doi": "10.1016/j.lfs.2022.120955", "doi_url": "https://doi.org/10.1016/j.lfs.2022.120955", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/36115583/", "url": "https://h2medicine.org/studies/study-aoki-2022-pregnancy-maintenance-mitochondrial-t-cells/", "methods": [], "indications": [ "pregnancy", "womens-health", "immune-system", "mechanism" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "breath-test", "headline": "2022 · Aoki — Molecular hydrogen has a positive impact on pregnancy maintenance through enhancement of mitochondrial function and immunomodulatory effects on T cells", "summary": "Pregnant women with preterm birth produced measurably less endogenous H₂. In cell and mouse experiments, molecular hydrogen improved the mitochondrial function of T cells and dampened inflammatory responses — in the animal model, H₂ reduced T-cell-driven preterm births. (Life Sciences, 2022 — basic research with a clinical observational part.)", "assessment": "Notable because the study provides a mechanistic bridge: H₂ → mitochondrial function in T cells → immunomodulation → pregnancy maintenance. This fits the mechanistic picture of H₂ (selective antioxidant, mitochondrial action) and reaches into the sensitive area of women's health/pregnancy. Important — caution warranted: statements about pregnancy are delicate; this study justifies NO clinical recommendation of H₂ during pregnancy. Limitations honestly: the proof of effect comes from cell culture and mouse, not from an intervention study in humans. The human part is observational and shows only an association (low H₂ ↔ preterm birth), not cause and effect. Strength of evidence is therefore at the basic/mechanistic level.", "abstract": "AIMS: Molecular hydrogen (H2) has attracted growing interest because of its implications in various diseases. However, the molecular mechanisms underlying the remarkable effect of a small amount of H2 remain elusive. No knowledge has been available on the role of H2 in the etiology of pregnancy disorders or its direct influence on human immune cells. Since maternal immunity, T cells in particular, plays a critical role in pregnancy maintenance. We investigated the effects of H2 on T cells and its relation to preterm birth (PTB). MAIN METHODS: Exhaled H2 concentrations in pregnant women were measured and correlated with cytokine concentrations in maternal and umbilical cord blood. H2 was added to T cells collected from healthy donors, and differentiation and proliferation were examined. Energy metabolism was also examined. H2 was administered to mice and cytokine expression was compared. KEY FINDINGS: Our prospective observational study revealed that maternal production of H2 is significantly lower in pregnant women with PTB, suggesting its potential as a biomarker for predicting PTB. We found that H2 has clear associations with several maternal cytokines, and acts as an immunomodulator by exerting mitochondrial function in human T cells. Moreover, in vivo administration of H2 to pregnant mice regulated inflammatory responses and reduced PTB caused by T cell activation, which further supports the notion that H2 may contribute to prolonged gestation through its immunomodulatory effect. SIGNIFICANCE: Measuring maternal H2-production could be a potential clinical tool in the management of PTB, and H2 may have positive impact on pregnancy maintenance.", "conclusion": "Moreover, in vivo administration of H2 to pregnant mice regulated inflammatory responses and reduced PTB caused by T cell activation, which further supports the notion that H2 may contribute to prolonged gestation through its immunomodulatory effect. SIGNIFICANCE: Measuring maternal H2-production could be a potential clinical tool in the management of PTB, and H2 may have positive impact on pregna" }, { "pmid": "32912119", "year": 2021, "title": "Perspective of Molecular Hydrogen in the Treatment of Sepsis", "title_en": null, "title_de": "Perspektive des molekularen Wasserstoffs in der Behandlung der Sepsis", "journal": "Current Pharmaceutical Design", "authors": "Qi et al.", "author_search": "qi qi", "doi": "10.2174/1381612826666200909124936", "doi_url": "https://doi.org/10.2174/1381612826666200909124936", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32912119/", "url": "https://h2medicine.org/studies/study-qi-2021-sepsis-treatment/", "methods": [ "unspecified" ], "indications": [ "fundamentals", "oxidative-stress", "respiratory" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Qi — Perspective of Molecular Hydrogen in the Treatment of Sepsis", "summary": "In sepsis — the most common cause of death in intensive care units — molecular hydrogen (H₂) as a „medical gas“ shows a protective effect on several organs. The effect rests on anti-inflammatory, antioxidant and anti-apoptotic mechanisms. (Review, Current Pharmaceutical Design, 2021.)", "assessment": "The paper shows that, beyond the known fields of application (sport, metabolism, neuro), H₂ is also discussed in highly acute intensive care medicine — evidence of the breadth of the mechanism „selective antioxidant + anti-inflammatory“. For us it is only marginally relevant: sepsis is a clinical emergency scenario (inhalation of high H₂ concentrations), not the field of everyday H₂ water — transferring it to consumer products is not permissible. Limitation, stated honestly: a pure review (evidence level 4), no study of its own, no patient data, and the authors themselves stress that the mechanism remains „elusive“ — still unresolved.", "abstract": "Sepsis is the main cause of death in critically ill patients with no effective treatment. Sepsis is lifethreatening organ dysfunction due to a dysregulated host response to infection. As a novel medical gas, molecular hydrogen (H2) has a therapeutic effect on many diseases, such as sepsis. H2 treatment exerts multiple biological effects, which can effectively improve multiple organ injuries caused by sepsis. However, the underlying molecular mechanisms of hydrogen involved in the treatment of sepsis remain elusive, which are likely related to anti-inflammation, anti-oxidation, anti-apoptosis, regulation of autophagy and multiple signaling pathways. This review can help better understand the progress of hydrogen in the treatment of sepsis, and provide a theoretical basis for the clinical application of hydrogen therapy in sepsis in the future.", "conclusion": "However, the underlying molecular mechanisms of hydrogen involved in the treatment of sepsis remain elusive, which are likely related to anti-inflammation, anti-oxidation, anti-apoptosis, regulation of autophagy and multiple signaling pathways. This review can help better understand the progress of hydrogen in the treatment of sepsis, and provide a theoretical basis for the clinical application of" }, { "pmid": "33076798", "year": 2021, "title": "Neuroprotective and Preventative Effects of Molecular Hydrogen", "title_en": null, "title_de": "Neuroprotektive und präventive Effekte des molekularen Wasserstoffs", "journal": "Current Pharmaceutical Design", "authors": "Noda et al.", "author_search": "noda noda", "doi": "10.2174/1381612826666201019103020", "doi_url": "https://doi.org/10.2174/1381612826666201019103020", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33076798/", "url": "https://h2medicine.org/studies/study-noda-2021-neuroprotective-preventative/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "neurology", "oxidative-stress", "fundamentals" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Noda — Neuroprotective and Preventative Effects of Molecular Hydrogen", "summary": "Hydrogen (H₂) is neuroprotective: this review summarizes how daily H₂ could slow the progression of neurodegenerative diseases such as Parkinson's and Alzheimer's (for which there are still no specific drugs) — via antioxidant and anti-inflammatory effects and via a surprising stomach-brain connection. (Current Pharmaceutical Design, 2021.)", "assessment": "The review is relevant because it describes H₂, beyond its antioxidant status, as a modulator of endocrine and neurotrophic systems — providing a more nuanced explanation of how regular H₂ could protect the nervous system. For us it is connectable that the central mouse findings work with drinking H₂ („drinking H2“, „chronic intake“) — i.e. the consumption form that corresponds to our products. Nevertheless it is essential to stay strictly factual: Parkinson's and Alzheimer's are serious diseases; no preventive or curative promises may be derived from an animal review. Limitations, stated honestly: it is a review (evidence level 4), the evidence comes predominantly from mouse models without human confirmation, the sex-dependent effect complicates generalization, and the authors themselves concede that the actual molecular target of H₂ is still unknown.", "abstract": "One of the beneficial effects of molecular hydrogen (H2, hydrogen gas) is neuroprotection and prevention of neurological disorders. It is important and useful if taking H2 every day can prevent or ameliorate the progression of neurodegenerative disorders, such as Parkinson's disease or Alzheimer's disease, both lacking specific therapeutic drugs. There are several mechanisms of how H2 protects neuronal damage. Anti-oxidative, anti-inflammatory, and the regulation of the endocrine system via stomach-brain connection seem to play an important role. At the cellular and tissue level, H2 appears to prevent the production of reactive oxygen species (ROS), and not only hydroxy radical (•OH) but also superoxide. In Parkinson's disease model mice, chronic intake of H2 causes the release of ghrelin from the stomach. In Alzheimer's disease model mice, sex-different neuroprotection is observed by chronic intake of H2. In female mice, declines of estrogen and estrogen receptor-β (ERβ) are prevented by H2, upregulating brain-derived neurotrophic factor (BDNF) and its receptor, tyrosine kinase receptor B (TrkB). The question of how drinking H2 upregulates the release of ghrelin or attenuates the decline of estrogen remains to be investigated and the mechanism of how H2 modulates endocrine systems and the fundamental question of what or where is the target of H2 needs to be elucidated for a better understanding of the effects of H2.", "conclusion": "In female mice, declines of estrogen and estrogen receptor-β (ERβ) are prevented by H2, upregulating brain-derived neurotrophic factor (BDNF) and its receptor, tyrosine kinase receptor B (TrkB). The question of how drinking H2 upregulates the release of ghrelin or attenuates the decline of estrogen remains to be investigated and the mechanism of how H2 modulates endocrine systems and the fundament" }, { "pmid": "34717628", "year": 2021, "title": "Cell surface sphingomyelin: key role in cancer initiation, progression, and immune evasion.", "title_en": null, "title_de": "Sphingomyelin der Zelloberfläche: Schlüsselrolle bei Krebsentstehung, -progression und Immunevasion.", "journal": "Lipids in health and disease", "authors": "Tallima et al.", "author_search": "tallima tallima", "doi": "10.1186/s12944-021-01581-y", "doi_url": "https://doi.org/10.1186/s12944-021-01581-y", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/34717628/", "url": "https://h2medicine.org/studies/study-tallima-2021-cell-surface-sphingomyelin-key/", "methods": [ "unspecified" ], "indications": [ "cancer", "immune-system" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Tallima — Cell surface sphingomyelin: key role in cancer initiation, progression, and immune evasion.", "summary": "This review examines how excess sphingomyelin (SM) on the outer surface of cancer cells enables tumors to evade the immune system, resist apoptosis, and ignore growth-suppressor signals. The authors propose that targeting SM metabolism may open new avenues for cancer therapy. Note: molecular hydrogen is not a primary focus of this paper. (Lipids in Health and Disease, 2021.)", "assessment": "This is a narrative review, not a clinical or experimental study. It presents a biochemical hypothesis about SM's role in cancer — an area of genuine scientific interest — but does not report new data and does not test H₂ as an intervention. The connection to molecular hydrogen in this paper is limited to the role of hydrogen bonds in membrane physics, not to H₂ therapy. Readers seeking evidence for H₂ as an anti-cancer agent should consult dedicated H₂ intervention studies; this review provides relevant tumor-biology context only.", "abstract": "Cell surface biochemical changes, notably excessive increase in outer leaflet sphingomyelin (SM) content, are important in cancer initiation, growth, and immune evasion. Innumerable reports describe methods to initiate, promote, or enhance immunotherapy of clinically detected cancer, notwithstanding the challenges, if not impossibility, of identification of tumor-specific, or associated antigens, the lack of tumor cell surface membrane expression of major histocompatibility complex (MHC) class I alpha and β2 microglobulin chains, and lack of expression or accessibility of Fas and other natural killer cell immune checkpoint molecules. Conversely, SM synthesis and hydrolysis are increasingly implicated in initiation of carcinogenesis and promotion of metastasis. Surface membrane SM readily forms inter- and intra- molecular hydrogen bond network, which excessive tightness would impair cell-cell contact inhibition, inter- and intra-cellular signals, metabolic pathways, and susceptibility to host immune cells and mediators. The present review aims at clarifying the tumor immune escape mechanisms, which face common immunotherapeutic approaches, and attracting attention to an entirely different, neglected, key aspect of tumorigenesis associated with biochemical changes in the cell surface that lead to failure of contact inhibition, an instrumental tumorigenesis mechanism. Additionally, the review aims to provide evidence for surface membrane SM levels and roles in cells resistance to death, failure to respond to growth suppressor signals, and immune escape, and to suggest possible novel approaches to cancer control and cure.", "conclusion": "The present review aims at clarifying the tumor immune escape mechanisms, which face common immunotherapeutic approaches, and attracting attention to an entirely different, neglected, key aspect of tumorigenesis associated with biochemical changes in the cell surface that lead to failure of contact inhibition, an instrumental tumorigenesis mechanism. Additionally, the review aims to provide eviden" }, { "pmid": "34646423", "year": 2021, "title": "Combating Oxidative Stress and Inflammation in COVID-19 by Molecular Hydrogen Therapy: Mechanisms and Perspectives.", "title_en": null, "title_de": "Bekämpfung von oxidativem Stress und Entzündung bei COVID-19 durch molekulare Wasserstofftherapie: Mechanismen und Perspektiven.", "journal": "Oxidative medicine and cellular longevity", "authors": "Alwazeer et al.", "author_search": "alwazeer alwazeer", "doi": "10.1155/2021/5513868", "doi_url": "https://doi.org/10.1155/2021/5513868", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/34646423/", "url": "https://h2medicine.org/studies/study-alwazeer-2021-combating-oxidative-stress-inflammation/", "methods": [ "unspecified" ], "indications": [ "respiratory", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Alwazeer — Combating Oxidative Stress and Inflammation in COVID-19 by Molecular Hydrogen Therapy: Mechanisms and Perspectives.", "summary": "This review systematically examines how molecular hydrogen (H₂) could theoretically address the oxidative stress and uncontrolled inflammation at the heart of severe COVID-19 — including its ability to suppress NF-κB signaling and activate the Nrf2 antioxidant pathway. The authors stress that exact mechanisms and clinical efficacy still require verification. (Oxidative Medicine and Cellular Longevity, 2021.)", "assessment": "This is a review article, not a clinical trial. It provides a well-reasoned mechanistic framework for why H₂ could be beneficial in COVID-19, and cites preclinical and some early clinical studies. The authors are honest that clinical efficacy has not been firmly established. At the time of writing, COVID-19 was still very new, and the evidence landscape has shifted since 2021. This paper is valuable as background on H₂ mechanisms in cytokine-driven lung injury, but should not be interpreted as proof that H₂ therapy works against COVID-19 in practice.", "abstract": "COVID-19 is a widespread global pandemic with nearly 185 million confirmed cases and about four million deaths. It is caused by an infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which primarily affects the alveolar type II pneumocytes. The infection induces pathological responses including increased inflammation, oxidative stress, and apoptosis. This situation results in impaired gas exchange, hypoxia, and other sequelae that lead to multisystem organ failure and death. As summarized in this article, many interventions and therapeutics have been proposed and investigated to combat the viral infection-induced inflammation and oxidative stress that contributes to the etiology and pathogenesis of COVID-19. However, these methods have not significantly improved treatment outcomes. This may partly be attributable to their inability at restoring redox and inflammatory homeostasis, for which molecular hydrogen (H2), an emerging novel medical gas, may complement. Herein, we systematically review the antioxidative, anti-inflammatory, and antiapoptotic mechanisms of H2. Its small molecular size and nonpolarity allow H2 to rapidly diffuse through cell membranes and penetrate cellular organelles. H2 has been demonstrated to suppress NF-κB inflammatory signaling and induce the Nrf2/Keap1 antioxidant pathway, as well as to improve mitochondrial function and enhance cellular bioenergetics. Many preclinical and clinical studies have demonstrated the beneficial effects of H2 in varying diseases, including COVID-19. However, the exact mechanisms, primary modes of action, and its true clinical effects remain to be delineated and verified. Accordingly, additional mechanistic and clinical research into this novel medical gas to combat COVID-19 complications is warranted.", "conclusion": "However, the exact mechanisms, primary modes of action, and its true clinical effects remain to be delineated and verified. Accordingly, additional mechanistic and clinical research into this novel medical gas to combat COVID-19 complications is warranted." }, { "pmid": "34643743", "year": 2021, "title": "Amyloid β structural polymorphism, associated toxicity and therapeutic strategies.", "title_en": null, "title_de": "Strukturelle Polymorphie von Amyloid β, assoziierte Toxizität und therapeutische Strategien.", "journal": "Cellular and molecular life sciences : CMLS", "authors": "Oren et al.", "author_search": "oren oren", "doi": "10.1007/s00018-021-03954-z", "doi_url": "https://doi.org/10.1007/s00018-021-03954-z", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/34643743/", "url": "https://h2medicine.org/studies/study-oren-2021-amyloid-structural-polymorphism-associated/", "methods": [ "unspecified" ], "indications": [ "metabolic", "sports-exercise", "neurology" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Oren — Amyloid β structural polymorphism, associated toxicity and therapeutic strategies.", "summary": "This comprehensive review covers the many different structural forms (polymorphs) of amyloid-β (Aβ) — the protein fragment central to Alzheimer's disease — how they form, why some are more toxic than others, and what therapeutic strategies are being pursued to interfere with their aggregation. Molecular hydrogen is not a primary subject of this paper; the hydrogen bonds discussed are intramolecular protein bonds, not H₂ therapy. (Cellular and Molecular Life Sciences, 2021.)", "assessment": "This is a narrative review of Aβ structural biology and aggregation inhibitor research. It does not study molecular hydrogen as a therapeutic agent. The mention of „hydrogen bonds“ relates to protein chemistry, not H₂ gas. The review is a valuable reference for the neuroscience of amyloid disease and therapeutic targeting of Aβ aggregation, but has very limited direct relevance to H₂-medicine. Readers interested in H₂ and neurodegeneration should seek studies that specifically test H₂ administration in Alzheimer's models.", "abstract": "A review of the multidisciplinary scientific literature reveals a large variety of amyloid-β (Aβ) oligomeric species, differing in molecular weight, conformation and morphology. These species, which may assemble via either on- or off-aggregation pathways, exhibit differences in stability, function and neurotoxicity, according to different experimental settings. The conformations of the different Aβ species are stabilized by intra- and inter-molecular hydrogen bonds and by electrostatic and hydrophobic interactions, all depending on the chemical and physical environment (e.g., solvent, ions, pH) and interactions with other molecules, such as lipids and proteins. This complexity and the lack of a complete understanding of the relationship between the different Aβ species and their toxicity is currently dictating the nature of the inhibitor (or inducer)-based approaches that are under development for interfering with (or inducing) the formation of specific species and Aβ oligomerization, and for interfering with the associated downstream neurotoxic effects. Here, we review the principles that underlie the involvement of different Aβ oligomeric species in neurodegeneration, both in vitro and in preclinical studies. In addition, we provide an overview of the existing inhibitors (or inducers) of Aβ oligomerization that serve as potential therapeutics for neurodegenerative diseases. The review, which covers the exciting studies that have been published in the past few years, comprises three main parts: 1) on- and off-fibrillar assembly mechanisms and Aβ structural polymorphism; 2) interactions of Aβ with other molecules and cell components that dictate the Aβ aggregation pathway; and 3) targeting the on-fibrillar Aβ assembly pathway as a therapeutic approach.", "conclusion": "In addition, we provide an overview of the existing inhibitors (or inducers) of Aβ oligomerization that serve as potential therapeutics for neurodegenerative diseases. The review, which covers the exciting studies that have been published in the past few years, comprises three main parts: 1) on- and off-fibrillar assembly mechanisms and Aβ structural polymorphism; 2) interactions of Aβ with other " }, { "pmid": "34538034", "year": 2021, "title": "[Intestinal microbiote of athletes].", "title_en": null, "title_de": "Darmmikrobiota von Sportlern.", "journal": "Voprosy pitaniia", "authors": "Bragina et al.", "author_search": "bragina bragina", "doi": "10.33029/0042-8833-2021-90-4-36-52", "doi_url": "https://doi.org/10.33029/0042-8833-2021-90-4-36-52", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/34538034/", "url": "https://h2medicine.org/studies/study-bragina-2021-intestinal-microbiote-athletes/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "sports-exercise", "cardiovascular", "respiratory", "eye" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Bragina — Intestinal microbiota of athletes.", "summary": "This systematic review of 14 studies finds that athletes harbour a more diverse gut microbiome than sedentary individuals, with higher proportions of bacteria that ferment complex carbohydrates into short-chain fatty acids — including species that use hydrogen gas (H₂) and formate to drive fermentation. H₂ appears here as a natural metabolic product of gut fermentation, not as an administered therapeutic. (Voprosy Pitaniya, 2021.)", "assessment": "This is a systematic review of observational cross-sectional studies, not an intervention trial. It describes associations between physical activity level and gut microbiome composition; causality cannot be established. The role of H₂ discussed here is endogenous gut H₂ from bacterial fermentation — a normal physiological process — not administered molecular hydrogen therapy. The evidence base is limited (14 studies, heterogeneous populations), and the review excludes dietary confounders imperfectly. Interesting as microbiome background, but not a study of H₂ supplementation.", "abstract": "The intestinal microbiota, due to new data on its functions obtained in the last decade, has become a new target point of influence on the organism. However, nowadays knowledge about the possible impact of physical activity and sports on the composition of the gut microbiota and, as a result, on the organism is limited. The aim of this review was to summarize current knowledge about the gut microbiota of healthy people with different levels of physical activity (from athletes to physically inactive people), and to identify patterns in the composition of the microbiota of various surveyed groups. Material and methods. A systematic search was carried out in electronic databases including EMBASE, MEDLINE, Web of Science, Google Scholar and eLIBRARY. The search process was carried out using keywords and logical operators. We included the following studies in our review: a) crossover studies comparing the gut microbiome of subjects with different physical activity; b) studies involving healthy adult women and men (18-45 years old); c) studies written in English and Russian. We excluded studies containing dietary changes, consumption of probiotics or prebiotics, and studies of physical activity in sick people. Results and discussion. Total 743 articles were received, of which 14 articles fully met the search criteria, and 101 articles partially corresponded. An analysis of the data from these studies indicated noticeable differences in the microbiota between athletes and people leading an sedentary lifestyle: the athletes had a greater α-diversity of the microbiota, while the level of microorganisms of the phylum Bacteroidetes was reduced; Akkermansiaceae and Faecalibacterium bacteria are elevated in athletes and people with active lifestyles. Different levels of physical activity in physically active people according to the levels of cardiorespiratory endurance did not affect the level of α- and β-diversity. When analyzing the effect of loads on the microbiota in various sports disciplines and skill levels, a connection was found with an increase in α-diversity in professionals and highly qualified athletes, with the relative content of series of bacteria (Methanobrevibacter smithii in professional cyclists; Parabacteroides, Phascolarctobacterium, Oscillibacter, Bilophila, Megasphaera in athletes of high martial arts qualifications of wushu; Eubacterium rectale, Polynucleobacter needarius, Faecalibacterium prausnitzii, Bacteroides vulgatus, Gordonibacter massiliensis in athletes of international level of various sports), and certain genera of bacteria have been identified (Parabacteroides, Phascolarctobacterium, Besilibacterium). Conclusion. The data obtained indicate a higher relative proportion of microbiota effective members, which are involved in the fermentation of complex polysaccharides and the production of short-chain fatty acids such as Faecalibacterium prausnitzii, Eubacterium hallii, Phascolarctobacterium, Eubacterium rectale, and Methanobrevibacter smithii, which increases the fermentation efficiency of many bacterial taxa in the gut by using hydrogen gas (H2) and formate to reduce carbon dioxide (CO2) to methane. There is a need to study other members of the microecological community, leading to a better understanding of the adaptation of the gut microbiota to levels of physical activity and its potentially positive effects on metabolism and endurance.", "conclusion": ". The data obtained indicate a higher relative proportion of microbiota effective members, which are involved in the fermentation of complex polysaccharides and the production of short-chain fatty acids such as Faecalibacterium prausnitzii, Eubacterium hallii, Phascolarctobacterium, Eubacterium rectale, and Methanobrevibacter smithii, which increases the fermentation efficiency of many bacterial taxa in the gut by using hydrogen gas (H2) and formate to reduce carbon dioxide (CO2) to methane. The" }, { "pmid": "34445428", "year": 2021, "title": "Molecular Hydrogen as a Novel Antitumor Agent: Possible Mechanisms Underlying Gene Expression.", "title_en": null, "title_de": "Molekularer Wasserstoff als neuartiges Antitumormittel: Mögliche zugrunde liegende Mechanismen der Genexpression.", "journal": "International journal of molecular sciences", "authors": "Hirano et al.", "author_search": "hirano hirano", "doi": "10.3390/ijms22168724", "doi_url": "https://doi.org/10.3390/ijms22168724", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/34445428/", "url": "https://h2medicine.org/studies/study-hirano-2021-antitumor-agent-possible-mechanisms/", "methods": [ "unspecified" ], "indications": [ "cancer", "immune-system", "oxidative-stress", "fundamentals-safety" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Hirano — Molecular Hydrogen as a Novel Antitumor Agent: Possible Mechanisms Underlying Gene Expression.", "summary": "This review surveys the growing evidence that molecular hydrogen (H₂) may act as an antitumor agent — not only by directly scavenging the most damaging reactive oxygen species (hydroxyl radicals), but also by regulating gene expression through indirect biological defense mechanisms. The authors emphasize that H₂ lacks the side effects of conventional anticancer drugs. (International Journal of Molecular Sciences, 2021.)", "assessment": "This is a narrative review, not a clinical trial. It presents a compelling mechanistic argument for H₂ as an antitumor agent, but the clinical evidence base for H₂ as a primary cancer treatment is still limited and largely preclinical. Most data originate from cell culture and animal models; human studies have primarily focused on tolerability and quality of life as an adjunct to conventional therapy. The review is useful for understanding proposed mechanisms, but should not be read as proof that H₂ treats cancer in humans.", "abstract": "While many antitumor drugs have yielded unsatisfactory therapeutic results, drugs are one of the most prevalent therapeutic measures for the treatment of cancer. The development of cancer largely results from mutations in nuclear DNA, as well as from those in mitochondrial DNA (mtDNA). Molecular hydrogen (H2), an inert molecule, can scavenge hydroxyl radicals (·OH), which are known to be the strongest oxidizing reactive oxygen species (ROS) in the body that causes these DNA mutations. It has been reported that H2 has no side effects, unlike conventional antitumor drugs, and that it is effective against many diseases caused by oxidative stress and chronic inflammation. Recently, there has been an increasing number of papers on the efficacy of H2 against cancer and its effects in mitigating the side effects of cancer treatment. In this review, we demonstrate the efficacy and safety of H2 as a novel antitumor agent and show that its mechanisms may not only involve the direct scavenging of ·OH, but also other indirect biological defense mechanisms via the regulation of gene expression.", "conclusion": "Recently, there has been an increasing number of papers on the efficacy of H2 against cancer and its effects in mitigating the side effects of cancer treatment. In this review, we demonstrate the efficacy and safety of H2 as a novel antitumor agent and show that its mechanisms may not only involve the direct scavenging of ·OH, but also other indirect biological defense mechanisms via the regulatio" }, { "pmid": "34281264", "year": 2021, "title": "Molecular Hydrogen as a Novel Protective Agent against Pre-Symptomatic Diseases.", "title_en": null, "title_de": "Molekularer Wasserstoff als neuartiges Schutzmittel gegen präsymptomatische Erkrankungen.", "journal": "International journal of molecular sciences", "authors": "Yamamoto et al.", "author_search": "yamamoto yamamoto", "doi": "10.3390/ijms22137211", "doi_url": "https://doi.org/10.3390/ijms22137211", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/34281264/", "url": "https://h2medicine.org/studies/study-yamamoto-2021-protective-agent-against-pre/", "methods": [ "unspecified" ], "indications": [ "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Yamamoto — Molecular Hydrogen as a Novel Protective Agent against Pre-Symptomatic Diseases.", "summary": "This review explores how molecular hydrogen (H₂) may help prevent „mibyou“ — the Japanese concept of pre-symptomatic illness in which disease silently develops before symptoms appear — by suppressing the chronic inflammation and oxidative stress that underlie many modern inflammatory conditions. (International Journal of Molecular Sciences, 2021.)", "assessment": "This is a conceptual review, not a clinical trial. The paper presents a coherent mechanistic hypothesis for H₂ as a preventive agent against chronic inflammation, grounded in existing preclinical data. The concept of pre-symptomatic disease prevention is clinically relevant, but demonstrating actual preventive efficacy in humans would require robust long-term intervention trials that do not yet exist. The review is best understood as a scientific rationale piece — not as evidence that H₂ prevents disease in practice.", "abstract": "Mibyou, or pre-symptomatic diseases, refers to state of health in which a disease is slowly developing within the body yet the symptoms are not apparent. Common examples of mibyou in modern medicine include inflammatory diseases that are caused by chronic inflammation. It is known that chronic inflammation is triggered by the uncontrolled release of proinflammatory cytokines by neutrophils and macrophages in the innate immune system. In a recent study, it was shown that molecular hydrogen (H2) has the ability to treat chronic inflammation by eliminating hydroxyl radicals (·OH), a mitochondrial reactive oxygen species (ROS). In doing so, H2 suppresses oxidative stress, which is implicated in several mechanisms at the root of chronic inflammation, including the activation of NLRP3 inflammasomes. This review explains these mechanisms by which H2 can suppress chronic inflammation and studies its applications as a protective agent against different inflammatory diseases in their pre-symptomatic state. While mibyou cannot be detected nor treated by modern medicine, H2 is able to suppress the pathogenesis of pre-symptomatic diseases, and thus exhibits prospects as a novel protective agent.", "conclusion": "This review explains these mechanisms by which H2 can suppress chronic inflammation and studies its applications as a protective agent against different inflammatory diseases in their pre-symptomatic state. While mibyou cannot be detected nor treated by modern medicine, H2 is able to suppress the pathogenesis of pre-symptomatic diseases, and thus exhibits prospects as a novel protective agent." }, { "pmid": "33945834", "year": 2021, "title": "How the brain fights fatty acids' toxicity.", "title_en": null, "title_de": "Wie das Gehirn die Toxizität von Fettsäuren bekämpft.", "journal": "Neurochemistry international", "authors": "Schönfeld et al.", "author_search": "schönfeld schönfeld", "doi": "10.1016/j.neuint.2021.105050", "doi_url": "https://doi.org/10.1016/j.neuint.2021.105050", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33945834/", "url": "https://h2medicine.org/studies/study-schoenfeld-2021-how-brain-fights-fatty/", "methods": [ "unspecified" ], "indications": [ "metabolic", "neurology", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Schönfeld — How the brain fights fatty acids' toxicity.", "summary": "This review explains why neurons, unlike most other cells, avoid using fatty acids as fuel — and describes the multiple biological strategies the brain has evolved to protect itself against lipotoxicity. Molecular hydrogen as a therapeutic is not the subject of this paper; hydrogen bonds appear only in their standard biochemical role within the discussed metabolic pathways. (Neurochemistry International, 2021.)", "assessment": "This is a narrative review of brain lipid metabolism and neuronal lipotoxicity protection. It does not study molecular hydrogen (H₂) as a therapeutic agent. References to „hydrogen“ in this paper are biochemical (fatty acid hydrogen atoms, FADH₂, etc.) — not to H₂ gas therapy. This paper provides important background on neuronal metabolism and ROS biology, but is only tangentially relevant to H₂-medicine. Readers should not interpret this as evidence for or against H₂ supplementation in neurological conditions.", "abstract": "Neurons spurn hydrogen-rich fatty acids for energizing oxidative ATP synthesis, contrary to other cells. This feature has been mainly attributed to a lower yield of ATP per reduced oxygen, as compared to glucose. Moreover, the use of fatty acids as hydrogen donor is accompanied by severe β-oxidation-associated ROS generation. Neurons are especially susceptible to detrimental activities of ROS due to their poor antioxidative equipment. It is also important to note that free fatty acids (FFA) initiate multiple harmful activities inside the cells, particularly on phosphorylating mitochondria. Several processes enhance FFA-linked lipotoxicity in the cerebral tissue. Thus, an uptake of FFA from the circulation into the brain tissue takes place during an imbalance between energy intake and energy expenditure in the body, a situation similar to that during metabolic syndrome and fat-rich diet. Traumatic or hypoxic brain injuries increase hydrolytic degradation of membrane phospholipids and, thereby elevate the level of FFA in neural cells. Accumulation of FFA in brain tissue is markedly associated with some inherited neurological disorders, such as Refsum disease or X-linked adrenoleukodystrophy (X-ALD). What are strategies protecting neurons against FFA-linked lipotoxicity? Firstly, spurning the β-oxidation pathway in mitochondria of neurons. Secondly, based on a tight metabolic communication between neurons and astrocytes, astrocytes donate metabolites to neurons for synthesis of antioxidants. Further, neuronal autophagy of ROS-emitting mitochondria combined with the transfer of degradation-committed FFA for their disposal in astrocytes, is a potent protective strategy against ROS and harmful activities of FFA. Finally, estrogens and neurosteroids are protective as triggers of ERK and PKB signaling pathways, consequently initiating the expression of various neuronal survival genes via the formation of cAMP response element-binding protein (CREB).", "conclusion": "Further, neuronal autophagy of ROS-emitting mitochondria combined with the transfer of degradation-committed FFA for their disposal in astrocytes, is a potent protective strategy against ROS and harmful activities of FFA. Finally, estrogens and neurosteroids are protective as triggers of ERK and PKB signaling pathways, consequently initiating the expression of various neuronal survival genes via t" }, { "pmid": "33925430", "year": 2021, "title": "Molecular Hydrogen as a Potential Clinically Applicable Radioprotective Agent.", "title_en": null, "title_de": "Molekularer Wasserstoff als potenziell klinisch anwendbares Radioprotektivum.", "journal": "International journal of molecular sciences", "authors": "Hirano et al.", "author_search": "hirano hirano", "doi": "10.3390/ijms22094566", "doi_url": "https://doi.org/10.3390/ijms22094566", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33925430/", "url": "https://h2medicine.org/studies/study-hirano-2021-clinically-applicable-radioprotective-agent/", "methods": [ "unspecified" ], "indications": [ "cancer", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Hirano — Molecular Hydrogen as a Potential Clinically Applicable Radioprotective Agent.", "summary": "This review compiles animal and early clinical evidence showing that molecular hydrogen (H₂) can protect against radiation-induced damage — both in diagnostic and therapeutic radiation contexts — primarily by selectively scavenging the hydroxyl radicals (·OH) generated when ionizing radiation hits water molecules. (International Journal of Molecular Sciences, 2021.)", "assessment": "This is a narrative review, not a clinical trial. It makes a well-grounded mechanistic case for H₂ radioprotection and summarizes existing animal and early human data favorably. The safety profile of H₂ appears to be a genuine strength of this approach. However, large-scale clinical evidence for radioprotection in humans is still limited, and the author's known advocacy position should be kept in mind. This review is valuable as a comprehensive overview of proposed mechanisms and early evidence, but clinical applicability must await more rigorous trials.", "abstract": "Although ionizing radiation (radiation) is commonly used for medical diagnosis and cancer treatment, radiation-induced damages cannot be avoided. Such damages can be classified into direct and indirect damages, caused by the direct absorption of radiation energy into DNA and by free radicals, such as hydroxyl radicals (•OH), generated in the process of water radiolysis. More specifically, radiation damage concerns not only direct damages to DNA, but also secondary damages to non-DNA targets, because low-dose radiation damage is mainly caused by these indirect effects. Molecular hydrogen (H2) has the potential to be a radioprotective agent because it can selectively scavenge •OH, a reactive oxygen species with strong oxidizing power. Animal experiments and clinical trials have reported that H2 exhibits a highly safe radioprotective effect. This paper reviews previously reported radioprotective effects of H2 and discusses the mechanisms of H2, not only as an antioxidant, but also in intracellular responses including anti-inflammation, anti-apoptosis, and the regulation of gene expression. In doing so, we demonstrate the prospects of H2 as a novel and clinically applicable radioprotective agent.", "conclusion": "This paper reviews previously reported radioprotective effects of H2 and discusses the mechanisms of H2, not only as an antioxidant, but also in intracellular responses including anti-inflammation, anti-apoptosis, and the regulation of gene expression. In doing so, we demonstrate the prospects of H2 as a novel and clinically applicable radioprotective agent." }, { "pmid": "33899545", "year": 2021, "title": "Protective effects of molecular hydrogen on lung injury from lung transplantation.", "title_en": null, "title_de": "Schützende Wirkungen von molekularem Wasserstoff auf Lungenschäden bei Lungentransplantation.", "journal": "Experimental biology and medicine (Maywood, N.J.)", "authors": "Quan et al.", "author_search": "quan quan", "doi": "10.1177/15353702211007084", "doi_url": "https://doi.org/10.1177/15353702211007084", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33899545/", "url": "https://h2medicine.org/studies/study-quan-2021-protective-lung-injury-lung/", "methods": [ "inhalation", "saline-iv", "bath-topical", "drinking-hrw" ], "indications": [ "respiratory", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Quan — Protective effects of molecular hydrogen on lung injury from lung transplantation.", "summary": "This review synthesizes the experimental evidence showing that H₂ — administered via inhalation, drinking, injection, or topical bath — can reduce the oxidative stress and inflammation responsible for primary graft dysfunction after lung transplantation. All reviewed evidence comes from animal models; clinical translation requires further trials. (Experimental Biology and Medicine, 2021.)", "assessment": "This is a review of animal studies — no clinical trial data in humans are available for H₂ in lung transplantation. The consistent preclinical signal across multiple delivery routes is encouraging and the mechanistic rationale is sound. The clinical need is real: primary graft dysfunction is a major unsolved problem in lung transplantation. However, the gap between animal models (typically rodents or large animals) and the complexity of human lung transplantation is significant. Clinical trials are explicitly identified by the authors as the required next step.", "abstract": "Lung grafts may experience multiple injuries during lung transplantation, such as warm ischaemia, cold ischaemia, and reperfusion injury. These injuries all contribute to primary graft dysfunction, which is a major cause of morbidity and mortality after lung transplantation. As a potential selective antioxidant, hydrogen molecule (H2) protects against post-transplant complications in animal models of multiple organ transplantation. Herein, the authors review the current literature regarding the effects of H2 on lung injury from lung transplantation. The reviewed studies showed that H2 improved the outcomes of lung transplantation by decreasing oxidative stress and inflammation at the donor and recipient phases. H2 is primarily administered via inhalation, drinking hydrogen-rich water, hydrogen-rich saline injection, or a hydrogen-rich water bath. H2 favorably modulates signal transduction and gene expression, resulting in the suppression of pro-inflammatory cytokines and excess reactive oxygen species production. Although H2 appears to be a physiological regulatory molecule with antioxidant, anti-inflammatory and anti-apoptotic properties, its exact mechanisms of action remain elusive. Taken together, accumulating experimental evidence indicates that H2 can significantly alleviate transplantation-related lung injury, mainly via inhibition of inflammatory cytokine secretion and reduction in oxidative stress through several underlying mechanisms. Further animal experiments and preliminary human clinical trials will lay the foundation for the use of H2 as a treatment in the clinic.", "conclusion": "Taken together, accumulating experimental evidence indicates that H2 can significantly alleviate transplantation-related lung injury, mainly via inhibition of inflammatory cytokine secretion and reduction in oxidative stress through several underlying mechanisms. Further animal experiments and preliminary human clinical trials will lay the foundation for the use of H2 as a treatment in the clinic." }, { "pmid": "33806292", "year": 2021, "title": "Potential Therapeutic Applications of Hydrogen in Chronic Inflammatory Diseases: Possible Inhibiting Role on Mitochondrial Stress.", "title_en": null, "title_de": "Mögliche therapeutische Anwendungen von Wasserstoff bei chronisch-entzündlichen Erkrankungen: Mögliche hemmende Rolle bei mitochondrialem Stress.", "journal": "International journal of molecular sciences", "authors": "Hirano et al.", "author_search": "hirano hirano", "doi": "10.3390/ijms22052549", "doi_url": "https://doi.org/10.3390/ijms22052549", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33806292/", "url": "https://h2medicine.org/studies/study-hirano-2021-therapeutic-applications-chronic-inflammatory/", "methods": [ "unspecified" ], "indications": [ "respiratory", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Hirano — Potential Therapeutic Applications of Hydrogen in Chronic Inflammatory Diseases: Possible Inhibiting Role on Mitochondrial Stress.", "summary": "This review proposes a mechanism by which molecular hydrogen (H₂) may inhibit NLRP3 inflammasome activation — a central driver of chronic inflammation — by reducing reactive oxygen species (ROS) produced inside mitochondria. The authors suggest this pathway could explain H₂'s potential in chronic inflammatory diseases including COVID-19. (International Journal of Molecular Sciences, 2021.)", "assessment": "This is a hypothesis review, not a clinical trial. The NLRP3 inflammasome connection is a scientifically compelling and currently active research area. The proposed mechanism — H₂ → mitochondrial ·OH scavenging → NLRP3 inhibition → reduced chronic inflammation — is coherent and anchored in existing biochemistry. However, the authors explicitly label it as a hypothesis. Experimental validation (especially in human disease) is still largely lacking. This paper is best read as a mechanistic framework piece that motivates further research.", "abstract": "Mitochondria are the largest source of reactive oxygen species (ROS) and are intracellular organelles that produce large amounts of the most potent hydroxyl radical (·OH). Molecular hydrogen (H2) can selectively eliminate ·OH generated inside of the mitochondria. Inflammation is induced by the release of proinflammatory cytokines produced by macrophages and neutrophils. However, an uncontrolled or exaggerated response often occurs, resulting in severe inflammation that can lead to acute or chronic inflammatory diseases. Recent studies have reported that ROS activate NLRP3 inflammasomes, and that this stimulation triggers the production of proinflammatory cytokines. It has been shown in literature that H2 can be based on the mechanisms that inhibit mitochondrial ROS. However, the ability for H2 to inhibit NLRP3 inflammasome activation via mitochondrial oxidation is poorly understood. In this review, we hypothesize a possible mechanism by which H2 inhibits mitochondrial oxidation. Medical applications of H2 may solve the problem of many chronic inflammation-based diseases, including coronavirus disease 2019 (COVID-19).", "conclusion": "In this review, we hypothesize a possible mechanism by which H2 inhibits mitochondrial oxidation. Medical applications of H2 may solve the problem of many chronic inflammation-based diseases, including coronavirus disease 2019 (COVID-19)." }, { "pmid": "33769417", "year": 2021, "title": "Inhaled gases as novel neuroprotective therapies in the postcardiac arrest period.", "title_en": null, "title_de": "Inhalierte Gase als neuartige neuroprotektive Therapien in der Phase nach Herzstillstand.", "journal": "Current opinion in critical care", "authors": "Magliocca et al.", "author_search": "magliocca magliocca", "doi": "10.1097/mcc.0000000000000820", "doi_url": "https://doi.org/10.1097/mcc.0000000000000820", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33769417/", "url": "https://h2medicine.org/studies/study-magliocca-2021-inhaled-gases-neuroprotective-therapies/", "methods": [ "inhalation" ], "indications": [ "neurology", "fundamentals-safety" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Magliocca et al. — Inhaled gases as novel neuroprotective therapies in the postcardiac arrest period.", "summary": "After cardiac arrest, inhaled gases such as xenon, argon, nitric oxide, and molecular hydrogen (H₂) have shown neuroprotective properties in experimental models. This review summarises the current evidence from preclinical and early clinical studies and points to the need for large randomised trials before any clinical recommendation can be made. (Current Opinion in Critical Care, 2021.)", "assessment": "This is a narrative review — no new experimental data, no meta-analytic pooling. Its value lies in synthesising the state of the field in 2021. For H₂ specifically, the evidence base at the time of writing was almost entirely preclinical; the review correctly flags this. Honest limitation: review articles from authors embedded in a research area can lean optimistic; critical appraisal of individual studies is not the primary purpose here. Clinical translation for H₂ in post-arrest neuroprotection remains an open research question.", "abstract": "PURPOSE OF REVIEW: The purpose of this review is to summarize recent advances about inhaled gases as novel neuroprotective agents in the postcardiac arrest period. RECENT FINDINGS: Inhaled gases, as nitric oxide (NO) and molecular hydrogen (H2), and noble gases as xenon (Xe) and argon (Ar) have shown neuroprotective properties after resuscitation. In experimental settings, the protective effect of these gases has been demonstrated in both in-vitro studies and animal models of cardiac arrest. They attenuate neuronal degeneration and improve neurological function after resuscitation acting on different pathophysiological pathways. Safety of both Xe and H2 after cardiac arrest has been reported in phase 1 clinical trials. A randomized phase 2 clinical trial showed the neuroprotective effects of Xe, combined with targeted temperature management. Xe inhalation for 24 h after resuscitation preserves white matter integrity as measured by fractional anisotropy of diffusion tensor MRI. SUMMARY: Inhaled gases, as Xe, Ar, NO, and H2 have consistently shown neuroprotective effects in experimental studies. Ventilation with these gases appears to be well tolerated in pigs and in preliminary human trials. Results from phase 2 and 3 clinical trials are needed to assess their efficacy in the treatment of postcardiac arrest brain injury.", "conclusion": "Ventilation with these gases appears to be well tolerated in pigs and in preliminary human trials. Results from phase 2 and 3 clinical trials are needed to assess their efficacy in the treatment of postcardiac arrest brain injury." }, { "pmid": "33762390", "year": 2021, "title": "Hydrogen treatment: a novel option in liver diseases.", "title_en": null, "title_de": "Wasserstoffbehandlung: eine neuartige Option bei Lebererkrankungen.", "journal": "Clinical medicine (London, England)", "authors": "Shi et al.", "author_search": "shi shi", "doi": "10.7861/clinmed.2020-0370", "doi_url": "https://doi.org/10.7861/clinmed.2020-0370", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33762390/", "url": "https://h2medicine.org/studies/study-shi-2021-option-liver-diseases/", "methods": [ "unspecified" ], "indications": [ "liver", "sports-exercise", "cancer", "immune-system", "oxidative-stress", "fundamentals-safety" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Shi et al. — Hydrogen treatment: a novel option in liver diseases.", "summary": "Hydrogen therapy shows promise in a range of liver conditions — from fatty liver disease to hepatitis B and chemotherapy-induced liver dysfunction — acting through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms. This review maps the available evidence and identifies key open questions for future research. (Clinical Medicine, 2021.)", "assessment": "This is a review article, not an original trial. Its value is as a synthesis of scattered findings across liver-related H₂ research up to 2021. The evidence base is heterogeneous — different disease models, different H₂ delivery methods, different outcome measures — which limits firm conclusions. The cautious framing by the authors is appropriate. Honest note: most of the mechanistic evidence cited derives from animal or in-vitro studies; direct clinical evidence in humans is still sparse for most liver indications discussed.", "abstract": "Hydrogen therapy is a very promising treatment against several diseases due to its mild attributes, high affinity and inherent biosafety. However, there is little elaboration about current hydrogen treatment in liver diseases. This article introduces the administration of hydrogen and mechanisms of hydrogen therapy in vivo, including modulating reactive oxygen species, apoptosis and autophagy, and inflammation, affecting mitochondria, as well as protein transporters. The major focus is clinical hydrogen use and related mechanisms in liver dysfunction or diseases, including non-alcoholic fatty liver disease, hepatitis B, liver dysfunction caused by liver tumour and colorectal tumour chemotherapy. Further, the article reveals ex vivo hydrogen application in liver protection. Finally, the article discusses the current and future challenges of hydrogen therapy in liver diseases, aiming to improve knowledge of hydrogen therapy and provide some insights into this burgeoning field.", "conclusion": "Further, the article reveals ex vivo hydrogen application in liver protection. Finally, the article discusses the current and future challenges of hydrogen therapy in liver diseases, aiming to improve knowledge of hydrogen therapy and provide some insights into this burgeoning field." }, { "pmid": "33719401", "year": 2021, "title": "Chemical and Biochemical Aspects of Molecular Hydrogen in Treating Kawasaki Disease and COVID-19.", "title_en": null, "title_de": "Chemische und biochemische Aspekte von molekularem Wasserstoff bei der Behandlung des Kawasaki-Syndroms und von COVID-19.", "journal": "Chemical research in toxicology", "authors": "Chen et al.", "author_search": "chen chen", "doi": "10.1021/acs.chemrestox.0c00456", "doi_url": "https://doi.org/10.1021/acs.chemrestox.0c00456", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33719401/", "url": "https://h2medicine.org/studies/study-chen-2021-chemical-biochemical-aspects-treating/", "methods": [ "inhalation" ], "indications": [ "cardiovascular", "respiratory", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Chen et al. — Chemical and Biochemical Aspects of Molecular Hydrogen in Treating Kawasaki Disease and COVID-19.", "summary": "Kawasaki disease and COVID-19 both involve damaging vascular inflammation; this review explores the chemical and biochemical rationale for using inhaled molecular hydrogen (H₂) in both conditions. H₂ is presented as a stable antioxidant that targets oxidative damage, inflammation, and abnormal blood vessel inflammation. (Chemical Research in Toxicology, 2021.)", "assessment": "This is a mechanistic review — it presents a biochemical plausibility argument for H₂ in Kawasaki disease and COVID-19, not clinical trial evidence. The hypothesis is scientifically coherent given H₂'s known antioxidant and anti-inflammatory properties, but no controlled human trials in KD or COVID-19 are cited as completed evidence. The Chinese guideline inclusion is noteworthy but was based on limited data at the time. Readers should distinguish between mechanistic plausibility and proven clinical benefit.", "abstract": "Kawasaki disease (KD) is a systemic vasculitis and is the most commonly acquired heart disease among children in many countries, which was first reported 50 years ago in Japan. The 2019 coronavirus disease (COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) has been a pandemic in most of the world since 2020, and since late 2019 in China. Kawasaki-like disease caused by COVID-19 shares some symptoms with KD, referred to as multisystem inflammatory syndrome in children, and has been reported in the United States, Italy, France, England, and other areas of Europe, with an almost 6-10 times or more increase compared with previous years of KD prevalence. Hydrogen gas is a stable and efficient antioxidant, which has a positive effect on oxidative damage, inflammation, cell apoptosis, and abnormal blood vessel inflammation. This review reports the chemical and biochemical aspects of hydrogen gas inhalation in treating KD and COVID-19.", "conclusion": "Hydrogen gas is a stable and efficient antioxidant, which has a positive effect on oxidative damage, inflammation, cell apoptosis, and abnormal blood vessel inflammation. This review reports the chemical and biochemical aspects of hydrogen gas inhalation in treating KD and COVID-19." }, { "pmid": "33510842", "year": 2021, "title": "Hydrogen Gas: A Novel Type of Antioxidant in Modulating Sexual Organs Homeostasis.", "title_en": null, "title_de": "Wasserstoffgas: Ein neuartiger Typ von Antioxidans bei der Modulation der Homöostase der Geschlechtsorgane.", "journal": "Oxidative medicine and cellular longevity", "authors": "Zhang et al.", "author_search": "zhang zhang", "doi": "10.1155/2021/8844346", "doi_url": "https://doi.org/10.1155/2021/8844346", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33510842/", "url": "https://h2medicine.org/studies/study-zhang-2021-type-antioxidant-modulating-sexual/", "methods": [ "inhalation", "bath-topical" ], "indications": [ "cancer", "immune-system", "womens-health", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Zhang et al. — Hydrogen Gas: A Novel Type of Antioxidant in Modulating Sexual Organs Homeostasis.", "summary": "Molecular hydrogen (H₂) appears to benefit reproductive health in both males and females — from improving sperm motility and erectile function to protecting ovarian function and reducing uterine inflammation — acting primarily through antioxidant and anti-inflammatory mechanisms. This review synthesises preclinical findings across a wide range of reproductive endpoints. (Oxidative Medicine and Cellular Longevity, 2021.)", "assessment": "This is a review of preclinical literature — the great majority of evidence cited comes from animal models and in-vitro experiments. Results are not directly transferable to human reproductive health without dedicated clinical trials. The biological plausibility is reasonable given H₂'s antioxidant profile, but reproductive medicine is a sensitive area where preclinical-to-clinical translation has historically been unreliable. Honest limitation: no human randomised controlled trials on H₂ for any of the reproductive endpoints are cited; this remains a hypothesis-generating review.", "abstract": "Sex is a science of cutting edge but bathed in mystery. Coitus or sexual intercourse, which is at the core of sexual activities, requires healthy and functioning vessels to supply the pelvic region, thus contributing to clitoris erection and vaginal lubrication in female and penile erection in male. It is well known that nitric oxide (NO) is the main gas mediator of penile and clitoris erection. In addition, the lightest and diffusible gas molecule hydrogen (H2) has been shown to improve erectile dysfunction (ED), testis injuries, sperm motility in male, preserve ovarian function, protect against uterine inflammation, preeclampsia, and breast cancer in female. Mechanistically, H2 has strong abilities to attenuate excessive oxidative stress by selectively reducing cytotoxic oxygen radicals, modulate immunity and inflammation, and inhibit injuries-induced cell death. Therefore, H2 is a novel bioactive gas molecule involved in modulating sexual organs homeostasis.", "conclusion": "Mechanistically, H2 has strong abilities to attenuate excessive oxidative stress by selectively reducing cytotoxic oxygen radicals, modulate immunity and inflammation, and inhibit injuries-induced cell death. Therefore, H2 is a novel bioactive gas molecule involved in modulating sexual organs homeostasis." }, { "pmid": "33349213", "year": 2021, "title": "Hydrogen Gas Therapy: From Preclinical Studies to Clinical Trials.", "title_en": null, "title_de": "Wasserstoffgas-Therapie: Von präklinischen Studien zu klinischen Studien.", "journal": "Current pharmaceutical design", "authors": "Sano et al.", "author_search": "sano sano", "doi": "10.2174/1381612826666201221150857", "doi_url": "https://doi.org/10.2174/1381612826666201221150857", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33349213/", "url": "https://h2medicine.org/studies/study-sano-2021-preclinical-trials/", "methods": [ "inhalation", "saline-iv" ], "indications": [ "sports-exercise", "cardiovascular", "cancer", "respiratory", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Sano et al. — Hydrogen Gas Therapy: From Preclinical Studies to Clinical Trials.", "summary": "Hydrogen gas (H₂) has demonstrated broad therapeutic potential in preclinical and early clinical studies — from ischaemia-reperfusion injury to organ transplantation and emergency medicine — and appears safe, inexpensive, and easy to administer. This review by Sano and colleagues highlights key findings and describes a novel field delivery system for organ preservation. (Current Pharmaceutical Design, 2021.)", "assessment": "This review comes from a research group with direct clinical trial experience in H₂ (Sano et al. have published phase 1/2 data on H₂ inhalation after cardiac arrest). The optimistic framing reflects genuine clinical experience, not just wishful thinking. Honest note: the conclusion that H₂ is „highly effective for a wide range of conditions“ is stronger than the current evidence level fully supports — several cited trials are phase 1/2 or small-scale. The novel organ preservation delivery method is an interesting applied contribution. This review is a useful clinical perspective but should be read alongside more conservative systematic reviews.", "abstract": "BACKGROUND: Mounting evidence indicates that hydrogen gas (H2) is a versatile therapeutic agent, even at very low, non-combustible concentrations. The Chinese National Health and Medical Commission recently recommended the use of inhaled H2 in addition to O2 therapy in the treatment of COVID-19-associated pneumonia, and its effects extend to anti-tumor, anti-inflammatory and antioxidant actions. SUMMARY: In this review, we have highlighted key findings from preclinical research and recent clinical studies demonstrating that H2 reduces the organ damage caused by ischemia-reperfusion. We have also outlined the critical role this effect plays in a variety of medical emergencies, including myocardial infarction, hemorrhagic shock, and out-of-hospital cardiac arrest, as well as in organ transplantation. H2 is compared with established treatments such as targeted temperature management, and we have also discussed its possible mechanisms of action, including the recently identified suppression of TNF-α-mediated endothelial glycocalyx degradation by inhaled H2. In addition, our new method that enables H2 gas to be easily transported to emergency settings and quickly injected into an organ preservation solution at the site of donor organ procurement have been described. CONCLUSION: H2 is an easily administered, inexpensive and well-tolerated agent that is highly effective for a wide range of conditions in emergency medicine, as well as for preserving donated organs.", "conclusion": "H2 is an easily administered, inexpensive and well-tolerated agent that is highly effective for a wide range of conditions in emergency medicine, as well as for preserving donated organs." }, { "pmid": "33290194", "year": 2021, "title": "Hydrogen Commonly Applicable from Medicine to Agriculture: From Molecular Mechanisms to the Field.", "title_en": null, "title_de": "Wasserstoff – allgemein anwendbar von der Medizin bis zur Landwirtschaft: Von molekularen Mechanismen bis zur Praxis.", "journal": "Current pharmaceutical design", "authors": "Li et al.", "author_search": "li li", "doi": "10.2174/1381612826666201207220051", "doi_url": "https://doi.org/10.2174/1381612826666201207220051", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33290194/", "url": "https://h2medicine.org/studies/study-li-2021-commonly-applicable-medicine-agriculture/", "methods": [ "inhalation" ], "indications": [ "fundamentals-safety" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Li et al. — Hydrogen Commonly Applicable from Medicine to Agriculture: From Molecular Mechanisms to the Field.", "summary": "Beyond its medical applications, molecular hydrogen (H₂) shows substantial promise in agriculture — enhancing plant stress tolerance, improving crop quality and yield, prolonging shelf life, and even strengthening livestock resilience. This review presents H₂ as a bridge between human health research and sustainable food production. (Current Pharmaceutical Design, 2021.)", "assessment": "This review is notable for its cross-domain scope. For readers interested in H₂ in human health, the medical section serves as background context; the novel contribution is the agricultural application framework. Honest note: the evidence quality for agricultural H₂ is variable — some claims rest on field trial data, others on laboratory experiments. The enthusiasm for „hydrogen agriculture“ as a low-carbon solution carries a promotional tone. This is not a clinical review and contains no human health trial data.", "abstract": "The emerging field of hydrogen biology has to date mainly been applied in medicine. However, hydrogen biology can also enable positive outcomes in agriculture. Agriculture faces significant challenges resulting from a growing population, climate change, natural disasters, environmental pollution, and food safety issues. In fact, hydrogen agriculture is a practical application of hydrogen biology, which may assist in addressing many of these challenges. It has been demonstrated that hydrogen gas (H2) may enhance plant tolerance towards abiotic and biotic stresses, regulate plant growth and development, increase nutritional values, prolong the shelf life, and decrease the nitrite accumulation during the storage of vegetables, as well as increase the resilience of livestock to pathogens. Our field trials show that H2 may have a promising potential to increase yield and improve the quality of agricultural products. This review aims to elucidate mechanisms for a novel agricultural application of H2 in China. Future development of hydrogen agriculture is proposed as well. Obviously, hydrogen agriculture belongs to a low carbon economy, and has great potential to provide \"safe, tasty, healthy, and high-yield\" agricultural products so that it may improve the sustainability of agriculture.", "conclusion": "Future development of hydrogen agriculture is proposed as well. Obviously, hydrogen agriculture belongs to a low carbon economy, and has great potential to provide \"safe, tasty, healthy, and high-yield\" agricultural products so that it may improve the sustainability of agriculture." }, { "pmid": "33185158", "year": 2021, "title": "Hydrogen-induced Neuroprotection in Neonatal Hypoxic-ischemic Encephalopathy.", "title_en": null, "title_de": "Wasserstoffinduzierte Neuroprotektion bei neonataler hypoxisch-ischämischer Enzephalopathie.", "journal": "Current pharmaceutical design", "authors": "Domoki", "author_search": "domoki domoki", "doi": "10.2174/1381612826666201113095720", "doi_url": "https://doi.org/10.2174/1381612826666201113095720", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33185158/", "url": "https://h2medicine.org/studies/study-domoki-2021-induced-neuroprotection-neonatal-hypoxic/", "methods": [ "unspecified" ], "indications": [ "neurology", "cardiovascular", "immune-system", "oxidative-stress", "fundamentals-safety" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Domoki — Hydrogen-induced Neuroprotection in Neonatal Hypoxic-ischemic Encephalopathy.", "summary": "In animal models of neonatal hypoxic-ischemic encephalopathy (HIE) — a leading cause of brain damage in newborns — molecular hydrogen (H₂) has consistently shown neuroprotective effects, including preserved neurovascular function, neuronal survival, and cognitive outcomes. This review examines the preclinical evidence and identifies key gaps before clinical use can be considered. (Current Pharmaceutical Design, 2021.)", "assessment": "This is a preclinical review. All evidence cited is from animal models (rodents and piglets) — not from human neonates. The findings are encouraging: H₂ neuroprotection is reproducible and consistent across models, including the clinically relevant piglet. However, no human clinical trials in neonatal HIE with H₂ are cited as completed. The explicit honest statement that H₂ + hypothermia combination has not been tested is an important caveat. Clinical translation requires both combination safety data and efficacy data. Do not interpret this review as evidence that H₂ treats brain injury in newborns.", "abstract": "Hypoxic-ischemic encephalopathy (HIE) remains to be a major cause of morbidity, mortality and severe neurodevelopmental disability in term neonates. Moderate whole body hypothermia is an established, effective neuroprotective therapy to reduce mortality and long-term disability associated with HIE, however, research for adjunct therapies is still warranted to complement the effect of hypothermia. In the last decade, molecular hydrogen emerged as a simple, available, inexpensive substance with advantageous pharmacokinetics to ameliorate hypoxic-ischemic cellular damage. The present review examines the preclinical studies employing hydrogen to combat the deleterious consequences of hypoxic-ischemic insults in rodent and piglet HIE models. Hydrogen exerted unequivocal neuroprotective actions shown by preserved neurovascular function, neuronal viability, and neurocognitive functions in virtually all model species and hypoxic-ischemic insult types tested. Administration of hydrogen started in most studies after the hypoxic-ischemic insult enhancing the translational value of the findings. Among the explored mechanisms of hydrogen-induced neuroprotection, antioxidant, anti- apoptotic and anti-inflammatory effects appeared to be dominant. Unfortunately, the additive neuroprotective effect of hydrogen and therapeutic hypothermia has not yet been demonstrated, thus such studies are warranted to promote the clinical testing of molecular hydrogen as an adjunct neuroprotective treatment of HIE.", "conclusion": "Among the explored mechanisms of hydrogen-induced neuroprotection, antioxidant, anti- apoptotic and anti-inflammatory effects appeared to be dominant. Unfortunately, the additive neuroprotective effect of hydrogen and therapeutic hypothermia has not yet been demonstrated, thus such studies are warranted to promote the clinical testing of molecular hydrogen as an adjunct neuroprotective treatment o" }, { "pmid": "33185152", "year": 2021, "title": "Recent Advances in Molecular Hydrogen Research Reducing Exercise-Induced Oxidative Stress and Inflammation.", "title_en": null, "title_de": "Aktuelle Fortschritte in der Forschung zu molekularem Wasserstoff zur Reduktion von belastungsinduziertem oxidativem Stress und Entzündung.", "journal": "Current pharmaceutical design", "authors": "Nogueira et al.", "author_search": "nogueira nogueira", "doi": "10.2174/1381612826666201113100245", "doi_url": "https://doi.org/10.2174/1381612826666201113100245", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33185152/", "url": "https://h2medicine.org/studies/study-nogueira-2021-recent-advances-research-reducing/", "methods": [ "unspecified" ], "indications": [ "sports-exercise", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Nogueira et al. — Recent Advances in Molecular Hydrogen Research Reducing Exercise-Induced Oxidative Stress and Inflammation.", "summary": "Exercise-induced oxidative stress and inflammation — harmful when exercise is exhaustive — may be mitigated by molecular hydrogen (H₂), which has shown antioxidant and anti-inflammatory properties in both animal and human studies. This review summarises the current knowledge base and highlights the still-incomplete picture under physiological conditions like physical exercise. (Current Pharmaceutical Design, 2021.)", "assessment": "This is a review covering both animal and human studies, which is more informative than purely preclinical reviews. However, the human evidence base in 2021 for H₂ in exercise physiology was modest in volume and heterogeneous in design. The review does not perform a meta-analysis or systematic quality assessment of included studies. Honest note: the field is genuinely interesting and the biological rationale is sound, but practical recommendations on H₂ supplementation for athletes or exercisers cannot yet be firmly derived from this literature alone.", "abstract": "Physical exercise-induced oxidative stress and inflammation may be beneficial when exercise is a regular activity, but it is rather harmful when exercise is exhaustive and performed by unaccustomed organisms. Molecular hydrogen (H2) has recently appeared as a potent antioxidant and anti-inflammatory molecule in numerous pathological conditions. However, its role is relatively unknown under physiological conditions such as physical exercise. Therefore, this review summarizes the current knowledge of the H2, reducing oxidative stress and inflammation in physical exercise, reporting data from both animal and human studies.", "conclusion": "However, its role is relatively unknown under physiological conditions such as physical exercise. Therefore, this review summarizes the current knowledge of the H2, reducing oxidative stress and inflammation in physical exercise, reporting data from both animal and human studies." }, { "pmid": "33183204", "year": 2021, "title": "An Overview of Ovarian Cancer: Molecular Processes Involved and Development of Target-based Chemotherapeutics.", "title_en": null, "title_de": "Ein Überblick über Ovarialkarzinom: Beteiligte molekulare Prozesse und Entwicklung zielgerichteter Chemotherapeutika.", "journal": "Current topics in medicinal chemistry", "authors": "Shaik et al.", "author_search": "shaik shaik", "doi": "10.2174/1568026620999201111155426", "doi_url": "https://doi.org/10.2174/1568026620999201111155426", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33183204/", "url": "https://h2medicine.org/studies/study-shaik-2021-overview-ovarian-cancer-processes/", "methods": [ "unspecified" ], "indications": [ "cancer", "womens-health" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Shaik et al. — An Overview of Ovarian Cancer: Molecular Processes Involved and Development of Target-based Chemotherapeutics.", "summary": "Ovarian cancer remains one of the deadliest gynaecological cancers, with most patients diagnosed at an advanced stage; this review surveys the molecular processes driving the disease and the development of targeted chemotherapeutics to address them. The role of H₂ in this context is indirect — it appears in the broader indication scope — but the review itself is largely a molecular oncology overview. (Current Topics in Medicinal Chemistry, 2021.)", "assessment": "This is a molecular oncology review covering ovarian cancer biology and chemotherapeutic development. It does not present H₂-specific trial or mechanistic data for ovarian cancer. Its presence in an H₂ study collection reflects thematic overlap at the indication level (cancer, womens-health), but readers seeking evidence for H₂ in ovarian cancer will not find it in this paper. The review is valuable as background oncology literature but has limited direct relevance to H₂ therapy.", "abstract": "Ovarian cancer is one of the leading gynecologic diseases with a high mortality rate worldwide. Current statistical studies on cancer reveal that over the past two decades, the fifth most common cause of death related to cancer in females of the western world is ovarian cancer. In spite of significant strides made in genomics, proteomics and radiomics, there has been little progress in transitioning these research advances into effective clinical administration of ovarian cancer. Consequently, researchers have diverted their attention to finding various molecular processes involved in the development of this cancer and how these processes can be exploited to develop potential chemotherapeutics to treat this cancer. The present review gives an overview of these studies which may update the researchers on where we stand and where to go further. The unfortunate situation with ovarian cancer that still exists is that most patients with it do not show any symptoms until the disease has moved to an advanced stage. Undoubtedly, several targets-based drugs have been developed to treat it, but drug-resistance and the recurrence of this disease are still a problem. For the development of potential chemotherapeutics for ovarian cancer, however, some theoretical approaches have also been applied. A description of such methods and their success in this direction is also covered in this review.", "conclusion": "For the development of potential chemotherapeutics for ovarian cancer, however, some theoretical approaches have also been applied. A description of such methods and their success in this direction is also covered in this review." }, { "pmid": "33148420", "year": 2021, "title": "Recent advances in studies of molecular hydrogen in the treatment of pancreatitis.", "title_en": null, "title_de": "Aktuelle Fortschritte in Studien zu molekularem Wasserstoff bei der Behandlung der Pankreatitis.", "journal": "Life sciences", "authors": "Li et al.", "author_search": "li li", "doi": "10.1016/j.lfs.2020.118641", "doi_url": "https://doi.org/10.1016/j.lfs.2020.118641", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33148420/", "url": "https://h2medicine.org/studies/study-li-2021-recent-advances-pancreatitis/", "methods": [ "unspecified" ], "indications": [ "cancer", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Li et al. — Recent advances in studies of molecular hydrogen in the treatment of pancreatitis.", "summary": "Pancreatitis — a serious inflammatory disease of the pancreas with high mortality — has recently attracted interest in molecular hydrogen (H₂) as a potential treatment, acting through antioxidant, anti-inflammatory, anti-apoptotic, and immune-modulatory mechanisms. This review synthesises the available preclinical and mechanistic evidence. (Life Sciences, 2021.)", "assessment": "This is a preclinical and mechanistic review. The evidence base for H₂ in pancreatitis consists primarily of animal and in-vitro studies; this is not a clinical trial summary. The review provides a rigorous mechanistic framework but does not constitute clinical evidence that H₂ treats pancreatitis in humans. The pathways described are biologically plausible given H₂'s known properties. Human clinical trials specifically in pancreatitis are needed before any clinical conclusions can be drawn.", "abstract": "Pancreatitis is an inflammatory disease of the pancreas characterized by acinar cell injury and is associated with the abnormal release of trypsin, which results in high mortality due to systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). The inflammatory response, impaired autophagic flux, endoplasmic reticulum stress (ERS) and their interactions are involved in the development of pancreatitis. Molecular hydrogen (H2) is a novel antioxidant that possesses the features of selective scavenging of oxygen free radicals and nontoxic metabolites and has been shown to be efficacious for treating infection, injury, tumors, ischemia-reperfusion organ injury, metabolic disease and several other diseases. Recent studies have found that H2 is also useful in the treatment of pancreatitis, which may be related to the mechanism of antioxidative stress, anti-inflammation, anti-apoptosis, regulation of immunity and regulation of molecular pathways. This review focuses on the pathogenesis of pancreatitis and the research progress and potential mechanisms of H2 against pancreatitis to provide theoretical bases for future research and clinical application of H2 therapy for pancreatitis.", "conclusion": "Recent studies have found that H2 is also useful in the treatment of pancreatitis, which may be related to the mechanism of antioxidative stress, anti-inflammation, anti-apoptosis, regulation of immunity and regulation of molecular pathways. This review focuses on the pathogenesis of pancreatitis and the research progress and potential mechanisms of H2 against pancreatitis to provide theoretical b" }, { "pmid": "33078374", "year": 2021, "title": "Neuroprotective Effects of Molecular Hydrogen: A Critical Review.", "title_en": null, "title_de": "Neuroprotektive Wirkungen von molekularem Wasserstoff: Eine kritische Übersichtsarbeit.", "journal": "Neuroscience bulletin", "authors": "Chen et al.", "author_search": "chen chen", "doi": "10.1007/s12264-020-00597-1", "doi_url": "https://doi.org/10.1007/s12264-020-00597-1", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33078374/", "url": "https://h2medicine.org/studies/study-chen-2021-neuroprotective-critical-review/", "methods": [ "unspecified" ], "indications": [ "neurology", "immune-system", "fundamentals-safety" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Chen et al. — Neuroprotective Effects of Molecular Hydrogen: A Critical Review.", "summary": "Molecular hydrogen (H₂) has demonstrated protective effects across a wide range of nervous system disorders in both preclinical and clinical studies — including ischaemia/reperfusion injury, Parkinson's disease, and cognitive dysfunction — acting through antioxidant, anti-inflammatory, anti-apoptotic, and mitochondria-preserving mechanisms. This critical review by Chen and colleagues provides one of the most comprehensive summaries of the neuroprotection evidence as of 2021. (Neuroscience Bulletin, 2021.)", "assessment": "This is one of the more thorough H₂ neuroprotection reviews. Its „critical“ framing is relatively honest, though the overall tone is favourable. Important context: while clinical data are referenced for some conditions (e.g. Parkinson's disease has small human trials), many cited studies are preclinical. The conclusion that H₂ is a „simple and effective clinical therapy“ should be qualified: the evidence strength varies considerably by condition. For ischaemia-reperfusion and Parkinson's disease the human evidence is stronger; for conditions like anxiety or traumatic brain injury it is more preliminary. The review is a valuable reference but should not be taken as a uniform endorsement of H₂ for all listed conditions.", "abstract": "Molecular hydrogen (H2) is a physiologically inert gas. However, during the last 10 years, increasing evidence has revealed its biological functions under pathological conditions. More specifically, H2 has protective effects against a variety of diseases, particularly nervous system disorders, which include ischemia/reperfusion injury, traumatic injury, subarachnoid hemorrhage, neuropathic pain, neurodegenerative diseases, cognitive dysfunction induced by surgery and anesthesia, anxiety, and depression. In addition, H2 plays protective roles mainly through anti-oxidation, anti-inflammation, anti-apoptosis, the regulation of autophagy, and preservation of mitochondrial function and the blood-brain barrier. Further, H2 is easy to use and has neuroprotective effects with no major side-effects, indicating that H2 administration is a potential therapeutic strategy in clinical settings. Here we summarize the H2 donors and their pharmacokinetics. Meanwhile, we review the effectiveness and safety of H2 in the treatment of various nervous system diseases based on preclinical and clinical studies, leading to the conclusion that H2 can be a simple and effective clinical therapy for CNS diseases such as ischemia-reperfusion brain injury, Parkinson's disease, and diseases characterized by cognitive dysfunction. The potential mechanisms involved in the neuroprotective effect of H2 are also analyzed.", "conclusion": "Meanwhile, we review the effectiveness and safety of H2 in the treatment of various nervous system diseases based on preclinical and clinical studies, leading to the conclusion that H2 can be a simple and effective clinical therapy for CNS diseases such as ischemia-reperfusion brain injury, Parkinson's disease, and diseases characterized by cognitive dysfunction. The potential mechanisms involved " }, { "pmid": "32981497", "year": 2021, "title": "Role of Molecular Hydrogen in Skin Diseases and its Impact in Beauty.", "title_en": null, "title_de": "Die Rolle von molekularem Wasserstoff bei Hauterkrankungen und seine Auswirkung auf die Schönheit.", "journal": "Current pharmaceutical design", "authors": "Bajgai et al.", "author_search": "bajgai bajgai", "doi": "10.2174/1381612826666200925124235", "doi_url": "https://doi.org/10.2174/1381612826666200925124235", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32981497/", "url": "https://h2medicine.org/studies/study-bajgai-2021-skin-diseases-impact-beauty/", "methods": [ "unspecified" ], "indications": [ "sports-exercise", "skin-aging", "immune-system", "allergy", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Bajgai et al. — Role of Molecular Hydrogen in Skin Diseases and its Impact in Beauty.", "summary": "Oxidative stress and chronic inflammation are central drivers of skin diseases such as psoriasis, atopic dermatitis, and skin ageing; molecular hydrogen (H₂) may offer a therapeutic approach by targeting these mechanisms. This review summarises current knowledge on H₂'s role in dermatology and cosmetic skin health. (Current Pharmaceutical Design, 2021.)", "assessment": "This is a narrative review combining dermatology, cosmetic science, and H₂ biology. The mechanistic argument is plausible but the clinical evidence base for H₂ in skin conditions is thin. Honest limitation: the „beauty“ framing introduces a non-clinical perspective that may inflate the perceived relevance of limited data. Human clinical trials in H₂ dermatology are very few; most cited evidence is from laboratory or animal studies. The review is useful as a hypothesis-generating document, not as clinical evidence.", "abstract": "In today's society, healthy skin and a beautiful appearance are considered the foundation of general well-being. The skin is the largest organ of the body and plays an important role in protecting it against various hazards such as environmental, physical, chemical, and biological hazards. These factors include mediators that lead to oxidation reactions that produce reactive oxygen/nitrogen species and additional oxidants in the skin cells. An increase in oxidants beyond the antioxidant capacity of its defense system causes oxidative stress and chronic inflammation in the body. This response can cause further disruption of collagen fibers and hinder the functioning of skin cells that may result in the development of various skin diseases including psoriasis, atopic dermatitis, and aging. In this review, we summarized the present information related to the role of oxidative stress in the pathogenesis of dermatological disorders, and its impact on physical beauty and the daily lives of patients. We also discussed how molecular hydrogen exhibits a therapeutic effect against skin diseases via its effects on oxidative stress. Furthermore, findings from this summary review indicate that molecular hydrogen might be an effective treatment modality for the prevention and treatment of skin-related illnesses.", "conclusion": "We also discussed how molecular hydrogen exhibits a therapeutic effect against skin diseases via its effects on oxidative stress. Furthermore, findings from this summary review indicate that molecular hydrogen might be an effective treatment modality for the prevention and treatment of skin-related illnesses." }, { "pmid": "32767925", "year": 2021, "title": "Direct Targets and Subsequent Pathways for Molecular Hydrogen to Exert Multiple Functions: Focusing on Interventions in Radical Reactions.", "title_en": null, "title_de": "Direkte Zielstrukturen und nachgeschaltete Signalwege, über die molekularer Wasserstoff vielfältige Funktionen ausübt: Mit Fokus auf Eingriffe in Radikalreaktionen", "journal": "Current pharmaceutical design", "authors": "Ohta", "author_search": "ohta ohta", "doi": "10.2174/1381612826666200806101137", "doi_url": "https://doi.org/10.2174/1381612826666200806101137", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32767925/", "url": "https://h2medicine.org/studies/study-ohta-2021-direct-targets-subsequent-pathways/", "methods": [ "unspecified" ], "indications": [ "metabolic", "neurology", "cancer", "respiratory", "immune-system", "allergy", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Ohta — Direct Targets and Subsequent Pathways for Molecular Hydrogen to Exert Multiple Functions: Focusing on Interventions in Radical Reactions", "summary": "Molecular hydrogen (H₂) is not simply a passive antioxidant — it actively intervenes in radical chain reactions, modifying lipid peroxides and downstream signaling cascades. This review by the researcher who first demonstrated H₂'s antioxidant properties traces the molecular pathway from H₂'s initial reaction with hydroxyl radicals to its far-reaching effects on calcium signaling, transcription factors, and energy metabolism. It also explores H₂'s potential relevance to COVID-19, Alzheimer's disease, and advanced cancer — strictly at the mechanistic hypothesis level.", "assessment": "This is a valuable mechanistic synthesis from a founding researcher in the field. It offers the most detailed molecular model available for how H₂ might exert its multi-functional effects through a coherent radical-reaction pathway. Honest limitations: this is a review article, not new experimental data, and several proposed mechanisms (Nrf2 paradox, protein hydration effects, COVID-19 connection) remain at the hypothesis stage. The NFAT/Ca²⁺ signaling model is biologically plausible but requires confirmation in human studies. The paper does not constitute clinical evidence for any therapeutic application in humans.", "abstract": "Molecular hydrogen (H2) was long regarded as non-functional in mammalian cells. We overturned the concept by demonstrating that H2 exhibits antioxidant effects and protects cells against oxidative stress. Subsequently, it has been revealed that H2 has multiple functions in addition to antioxidant effects, including antiinflammatory, anti-allergic functions, and as cell death and autophagy regulation. Additionally, H2 stimulates energy metabolism. As H2 does not readily react with most biomolecules without a catalyst, it is essential to identify the primary targets with which H2 reacts or interacts directly. As a first event, H2 may react directly with strong oxidants, such as hydroxyl radicals (•OH) in vivo. This review addresses the key issues related to this in vivo reaction. •OH may have a physiological role because it triggers a free radical chain reaction and may be involved in the regulation of Ca2+- or mitochondrial ATP-dependent K+-channeling. In the subsequent pathway, H2 suppressed a free radical chain reaction, leading to decreases in lipid peroxide and its end products. Derived from the peroxides, 4-hydroxy-2-nonenal functions as a mediator that up-regulates multiple functional PGC-1α. As the other direct target in vitro and in vivo, H2 intervenes in the free radical chain reaction to modify oxidized phospholipids, which may act as an antagonist of Ca2+-channels. The resulting suppression of Ca2+-signaling inactivates multiple functional NFAT and CREB transcription factors, which may explain H2 multi-functionality. This review also addresses the involvement of NFAT in the beneficial role of H2 in COVID-19, Alzheimer's disease and advanced cancer. We discuss some unsolved issues of H2 action on lipopolysaccharide signaling, MAPK and NF-κB pathways and the Nrf2 paradox. Finally, as a novel idea for the direct targeting of H2, this review introduces the possibility that H2 causes structural changes in proteins via hydrate water changes.", "conclusion": "We discuss some unsolved issues of H2 action on lipopolysaccharide signaling, MAPK and NF-κB pathways and the Nrf2 paradox. Finally, as a novel idea for the direct targeting of H2, this review introduces the possibility that H2 causes structural changes in proteins via hydrate water changes." }, { "pmid": "32505123", "year": 2021, "title": "Hydrogen and therapeutic gases for neonatal hypoxic-ischemic encephalopathy: potential neuroprotective adjuncts in translational research.", "title_en": null, "title_de": "Wasserstoff und therapeutische Gase bei neonataler hypoxisch-ischämischer Enzephalopathie: potenzielle neuroprotektive Zusatztherapien in der translationalen Forschung", "journal": "Pediatric research", "authors": "Htun et al.", "author_search": "htun htun", "doi": "10.1038/s41390-020-0998-z", "doi_url": "https://doi.org/10.1038/s41390-020-0998-z", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32505123/", "url": "https://h2medicine.org/studies/study-htun-2021-therapeutic-gases-neonatal-hypoxic/", "methods": [ "inhalation" ], "indications": [ "neurology", "oxidative-stress", "fundamentals-safety" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Htun et al. — Hydrogen and Therapeutic Gases for Neonatal Hypoxic-Ischemic Encephalopathy: Potential Neuroprotective Adjuncts in Translational Research", "summary": "Neonatal hypoxic-ischemic encephalopathy (HIE) — brain injury in newborns caused by oxygen deprivation — remains without a fully effective treatment, and molecular hydrogen has emerged as a promising neuroprotective candidate. This review evaluates the evidence from translational animal models: hydrogen inhalation, alone or combined with therapeutic hypothermia, shows short- and long-term neuroprotection in neonatal HIE models. No large human trials exist yet.", "assessment": "This is a carefully framed translational review identifying hydrogen as a biologically plausible candidate for neonatal HIE. The mechanistic rationale (oxidative stress → selective H₂ scavenging) is sound and consistent with broader H₂ literature. Critical limitations to state honestly: all neuroprotection findings cited are from animal models (mainly rodent); no adequately powered randomized controlled trials in human neonates are yet available. The review is not a clinical recommendation. Translating from neonatal rat or piglet models to human premature or term newborns involves substantial uncertainty. This paper appropriately flags these gaps rather than overstating the evidence.", "abstract": "Numerous studies have examined the potential use of therapeutic gases for the treatment of various neurological disorders. Hydrogen gas, a promising neuroprotective agent, has been a focus of study due to its potent antioxidative properties. In translational research into adult diseases, hydrogen has been shown to be neuroprotective in disorders such as cerebral ischemia and traumatic brain injury, and in neurodegenerative diseases such as Alzheimer's disease. Animal and human studies have verified the safety and feasibility of molecular hydrogen. However, despite extensive research on its efficacy in adults, only a few studies have investigated its application in pediatric and neonatal medicine. Neonatal hypoxic-ischemic encephalopathy (HIE) is characterized by damage to neurons and other cells of the nervous system. One of the major contributing factors is excessive exposure to oxidative stress. Current research interest in HIE is shifting toward new neuroprotective agents, as single agents or as adjuncts to therapeutic hypothermia. Here, we review therapeutic gases, particularly hydrogen, and their potentials and limitations in the treatment of HIE in newborns. IMPACT: Translational animal models of neonatal HIE are a current focus of research into the therapeutic usefulness of various gases. Hydrogen ventilation as a single agent or in combination with therapeutic hypothermia shows short- and long-term neuroprotection in neonatal translational HIE models. The optimal target severity for therapeutic interventions should be well established to improve outcomes.", "conclusion": "Hydrogen ventilation as a single agent or in combination with therapeutic hypothermia shows short- and long-term neuroprotection in neonatal translational HIE models. The optimal target severity for therapeutic interventions should be well established to improve outcomes." }, { "pmid": "33356580", "year": 2021, "title": "Hydrotherapy with hydrogen-rich water compared with RICE protocol following acute ankle sprain in professional athletes: a randomized non-inferiority pilot trial", "title_en": null, "title_de": "Hydrotherapie mit wasserstoffreichem Wasser im Vergleich zum RICE-Protokoll nach akuter Knöchelverstauchung bei Profisportlern: eine randomisierte Nicht-Unterlegenheits-Pilotstudie", "journal": "Research in Sports Medicine", "authors": "Javorac et al.", "author_search": "javorac javorac", "doi": "10.1080/15438627.2020.1868468", "doi_url": "https://doi.org/10.1080/15438627.2020.1868468", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33356580/", "url": "https://h2medicine.org/studies/study-javorac-2021-ankle-sprain-rice-protocol-athletes/", "methods": [ "bath-topical", "drinking-hrw" ], "indications": [ "sports-exercise", "joints-rheumatology", "oxidative-stress" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2021 · Javorac — Hydrotherapy with hydrogen-rich water compared with RICE protocol following acute ankle sprain in professional athletes: a randomized non-inferiority pilot trial", "summary": "Hydrogen-rich baths were just as effective as the gold-standard RICE procedure (rest, ice, compression, elevation) for acute ankle sprain in professional athletes. In a randomized non-inferiority pilot trial (n = 18) there were no significant differences between H₂ hydrotherapy and RICE in swelling, range of motion and balance. (Research in Sports Medicine, 2021.)", "assessment": "Directly relevant for H₂ bath and hydrotherapy products in the sport sector — an everyday application with a large target group (club sport, physiotherapy practices). The finding should be read cautiously: equivalence, not superiority, was shown. That is nevertheless strong, because H₂ baths can be positioned as a more comfortable, warmer alternative to the unpleasant ice protocol. Limitation, stated honestly: very small sample (n = 18), pilot character, no blinding possible (a bath vs. ice are obviously different), and the non-inferiority margin is not quantified in the abstract. Mechanistically the effect fits the antioxidant/anti-inflammatory profile of H₂ in tissue trauma.", "abstract": "We analysed the effects of an experimental novel protocol of intensive hydrotherapy with hydrogen-rich water (HRW) on injury recovery in athletic men who suffered an acute ankle sprain (AAS) and compared it with a RICE protocol (rest, ice, compression, elevation). Professional athletes (age 23.7 ± 4.0 years; weight 78.6 ± 5.7 kg, height 182.5 ± 4.3 cm; professional experience 5.9 ± 3.9 years) who incurred AAS during a sport-related activity were randomly assigned immediately after the injury to either hydrogen group (n = 9) or a conventional RICE treatment group (n = 9). Hydrogen group received six 30-min ankle baths with HRW throughout the first 24 h post-injury, with hydrotherapy administered every 4 hours during the intervention period. RICE group stood off the injured leg, with ice packs administered for 20 min every 3 hours, with the injured ankle compressed with an elastic bandage for 24 hours and elevated at all possible times above the level of the heart. HRW was equivalent to RICE protocol to reduce ankle swelling (2.1 ± 0.9% vs. 1.6 ± 0.8%; P = 0.26), range of motion (2.4 ± 1.3 cm vs. 2.7 ± 0.8 cm; P = 0.60), and single-leg balance with eyes opened (18.4 ± 8.2 sec vs. 10.7 ± 8.0 sec; P = 0.06) and closed (5.6 ± 8.4 sec vs. 3.9 ± 4.2 sec; P = 0.59). This non-inferiority pilot trial supports the use of HRW as an effective choice in AAS management. However, more studies are needed to corroborate these findings in other soft tissue injuries.", "conclusion": "This non-inferiority pilot trial supports the use of HRW as an effective choice in AAS management. However, more studies are needed to corroborate these findings in other soft tissue injuries." }, { "pmid": "33573133", "year": 2021, "title": "Application of Molecular Hydrogen as an Antioxidant in Responses to Ventilatory and Ergogenic Adjustments during Incremental Exercise in Humans", "title_en": null, "title_de": "Anwendung von molekularem Wasserstoff als Antioxidans bei den Reaktionen von Atmung und ergogenen Anpassungen während stufenweiser Belastung beim Menschen", "journal": "Nutrients", "authors": "Alharbi et al.", "author_search": "alharbi alharbi", "doi": "10.3390/nu13020459", "doi_url": "https://doi.org/10.3390/nu13020459", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33573133/", "url": "https://h2medicine.org/studies/study-alharbi-2021-antioxidant-ventilatory-ergogenic-incremental-exercise/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise", "oxidative-stress" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2021 · Alharbi — Application of Molecular Hydrogen as an Antioxidant in Responses to Ventilatory and Ergogenic Adjustments during Incremental Exercise in Humans", "summary": "H₂ supplementation altered ventilatory and acid-base status during incremental exercise. In a randomized, double-blind crossover study (18 trained people), H₂-rich calcium powder led at rest to lower ventilation and higher bicarbonate — during exertion ventilation stayed lower. (Nutrients, 2021.)", "assessment": "Relevant for H₂-in-sport products (here H₂-rich calcium powder, comparable to the Mg-stick/HRW concept), but as an honest differentiation example: the study shows measurable physiological effects (ventilation, acid-base balance) but precisely NO increase in oxygen uptake — i.e. no crude performance proof. This is valuable for honest argumentation: H₂ intervenes in exercise physiology, but the benefit is nuanced and not a blanket „more performance“. Limitations honestly: small sample (n = 18), very low H₂ dose (2.544 µg/day), effects in part only in one of the two muscles studied, interpretation mechanistic-speculative. Methodologically strong, though: randomized, double-blind, crossover.", "abstract": "We investigated effects of molecular hydrogen (H2) supplementation on acid-base status, pulmonary gas exchange responses, and local muscle oxygenation during incremental exercise. Eighteen healthy, trained subjects in a randomized, double-blind, crossover design received H2-rich calcium powder (HCP) (1500 mg/day, containing 2.544 µg/day of H2) or H2-depleted placebo (1500 mg/day) for three consecutive days. They performed cycling incremental exercise starting at 20-watt work rate, increasing by 20 watts/2 min until exhaustion. Breath-by-breath pulmonary ventilation (V˙E) and CO2 output (V˙CO2) were measured and muscle deoxygenation (deoxy[Hb + Mb]) was determined via time-resolved near-infrared spectroscopy in the vastus lateralis (VL) and rectus femoris (RF). Blood gases' pH, lactate, and bicarbonate (HCO3-) concentrations were measured at rest and 120-, 200-, and 240-watt work rates. At rest, the HCP group had significantly lower V˙E, V˙CO2, and higher HCO3-, partial pressures of CO2 (PCO2) versus placebo. During exercise, a significant pH decrease and greater HCO3- continued until 240-watt workload in HCP. The V˙E was significantly lower in HCP versus placebo, but HCP did not affect the gas exchange status of V˙CO2 or oxygen uptake (V˙O2). HCP increased absolute values of deoxy[Hb + Mb] at the RF but not VL. Thus, HCP-induced hypoventilation would lead to lower pH and secondarily impaired balance between O2 delivery and utilization in the local RF during exercise, suggesting that HCP supplementation, which increases the at-rest antioxidant potential, affects the lower ventilation and pH status during incremental exercise. HPC induced a significantly lower O2 delivery/utilization ratio in the RF but not the VL, which may be because these regions possess inherently different vascular/metabolic control properties, perhaps related to fiber-type composition.", "conclusion": "Thus, HCP-induced hypoventilation would lead to lower pH and secondarily impaired balance between O2 delivery and utilization in the local RF during exercise, suggesting that HCP supplementation, which increases the at-rest antioxidant potential, affects the lower ventilation and pH status during incremental exercise. HPC induced a significantly lower O2 delivery/utilization ratio in the RF but no" }, { "pmid": "34319514", "year": 2021, "title": "Randomized double-blind placebo-controlled trial of hydrogen inhalation for Parkinson's disease: a pilot study", "title_en": null, "title_de": "Randomisierte doppelblinde placebokontrollierte Studie zur Wasserstoff-Inhalation bei der Parkinson-Krankheit: eine Pilotstudie", "journal": "Neurological Sciences", "authors": "Yoritaka et al.", "author_search": "yoritaka yoritaka", "doi": "10.1007/s10072-021-05489-4", "doi_url": "https://doi.org/10.1007/s10072-021-05489-4", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/34319514/", "url": "https://h2medicine.org/studies/study-yoritaka-2021-inhalation-parkinson-disease/", "methods": [ "inhalation" ], "indications": [ "neurology", "oxidative-stress" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2021 · Yoritaka — Randomized double-blind placebo-controlled trial of hydrogen inhalation for Parkinson's disease: a pilot study", "summary": "Hydrogen inhalation was safe in Parkinson's — but showed no measurable benefit. In this randomized, double-blind, placebo-controlled pilot study (20 patients, 16 weeks), 6.5% H₂ gas did not significantly improve the Parkinson's scale over placebo. (Neurological Sciences, 2021.)", "assessment": "We deliberately include this study even though it is negative — a credible study database also shows where H₂ did not help. For us it is an anchor for honest communication: no cure-all promise. The value lies in the clean design (randomized, double-blind) and the safety finding. Limitation, stated honestly: very small sample (n = 20, of which 5 excluded → effectively 15), a pure pilot study without power for small effects, possible under-dosing or too short a duration. A null result in a pilot trial does not definitively refute H₂ in Parkinson's — it only shows that this specific approach produced no effect.", "abstract": "BACKGROUND: Oxidative stress is involved in the progression of Parkinson's disease (PD). Recent studies have confirmed that molecular hydrogen (H2) functions as a highly effective antioxidant in animal models of PD. A placebo-controlled, randomized, double-blind, parallel-group clinical pilot study was conducted to assess the efficacy of hydrogen gas inhalation in Japanese patients with PD on treatment with levodopa. METHODS: Twenty participants fulfilling the Movement Disorder Society criteria were enrolled. Participants inhaled 6.5 (0.1) vol% hydrogen gas in 2 L/min of mixed air or placebo air for 16 weeks, twice a day for 1 h. RESULTS: Five participants were excluded due to deviation from the protocol of the total duration of inhalation < 112 h. No significant differences were seen in the change in the total Movement Disorder Society Unified Parkinson's Disease Rating Scale score from baseline to the 16th week between the group that inhaled hydrogen gas and the group that inhaled placebo air (Mann-Whitney U test, p > 0.05). No adverse events were seen. The compliance to the protocol-based duration of inhalation time in all participants decreased with the elderly participants, the higher daily dose of levodopa, and the higher PDQ-39 items on emotions (n = 20, p < 0.05). CONCLUSION: This pilot study revealed that the inhalation of molecular hydrogen gas was safe, but did not show any beneficial effects in patients with PD. TRIAL REGISTRATION: UMIN ID: 000,039,217 (October 6, 2018).", "conclusion": "This pilot study revealed that the inhalation of molecular hydrogen gas was safe, but did not show any beneficial effects in patients with PD. TRIAL" }, { "pmid": "33349011", "year": 2021, "title": "Intravenous Hydrogen Therapy With Intracisternal Magnesium Sulfate Infusion in Severe Aneurysmal Subarachnoid Hemorrhage.", "title_en": null, "title_de": "Intravenöse Wasserstofftherapie mit intrazisternaler Magnesiumsulfat-Infusion bei schwerer aneurysmatischer Subarachnoidalblutung", "journal": "Stroke", "authors": "Takeuchi et al.", "author_search": "takeuchi takeuchi", "doi": "10.1161/strokeaha.120.031260", "doi_url": "https://doi.org/10.1161/strokeaha.120.031260", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33349011/", "url": "https://h2medicine.org/studies/study-takeuchi-2021-intravenous-intracisternal-magnesium-sulfate/", "methods": [ "saline-iv" ], "indications": [ "sports-exercise", "neurology" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2021 · Takeuchi — Intravenous Hydrogen Therapy With Intracisternal Magnesium Sulfate Infusion in Severe Aneurysmal Subarachnoid Hemorrhage", "summary": "In a three-arm randomised trial of 37 patients with life-threatening subarachnoid haemorrhage, adding intravenous hydrogen therapy to intracisternal magnesium sulphate infusion reduced brain injury biomarkers and delayed cerebral ischaemia compared to controls. Functional outcomes at one year were better in the combination group, though differences in recovery scores at 3 months did not reach significance. (Stroke, 2021.)", "assessment": "One of the most clinically serious H₂ RCTs published — high-stakes neurosurgical setting, multi-arm design, published in a top-tier journal, pre-registered (UMIN000014696). Limitations: n=37 is underpowered for firm conclusions; the intracisternal magnesium is itself an active intervention, making it difficult to cleanly isolate H₂'s contribution; modified Rankin Scale at 3 months did not differ significantly between groups; the intravenous H₂-saline route is not widely available outside specialist centres. The Barthel index improvement at 12 months and the biomarker reduction are the strongest H₂-specific signals. A properly powered follow-up RCT is warranted.", "abstract": "BACKGROUND AND PURPOSE: Poor-grade subarachnoid hemorrhage still has a poor prognosis. This randomized controlled clinical trial evaluated intracisternal magnesium sulfate infusion combined with intravenous hydrogen therapy in patients with poor-grade subarachnoid hemorrhage. METHODS: Thirty-seven patients with poor-grade subarachnoid hemorrhage were randomized to Mg+H2, Mg, and control groups. Mg and Mg+H2 groups received intracisternal magnesium sulfate infusion (2.5 mmol/L) at 20 mL/h for 14 days. Mg+H2 group also received intravenous hydrogen-rich solution infusion for 14 days. Primary outcome measures were occurrence of delayed cerebral ischemia and cerebral vasospasm. Secondary outcome measures were modified Rankin Scale and Karnofsky performance status at 3 and 12 months, Barthel index at 12 months, and serum and cerebrospinal fluid malondialdehyde and neuron-specific enolase. RESULTS: Serum neuron-specific enolase levels were significantly lower in the Mg+H2 group from days 3 to 14 than in the control group. Cerebrospinal fluid neuron-specific enolase levels were also significantly lower in the Mg+H2 group from days 3 to 7 than in the control group. Incidences of cerebral vasospasm and delayed cerebral ischemia were significantly higher in the control group than in other groups. Modified Rankin Scale and Karnofsky performance status did not significantly differ between the three groups at 3 months. Modified Rankin Scale scores 0 to 2 were more common in the Mg and Mg+H2 groups at 1 year. Barthel index was higher in the Mg+H2 group than in the control group. CONCLUSIONS: Intracisternal magnesium sulfate infusion started immediately after surgery reduces the incidence of cerebral vasospasm and delayed cerebral ischemia and improves clinical outcomes without complications in patients with poor-grade subarachnoid hemorrhage. Intracisternal magnesium sulfate infusion combined with intravenous hydrogen therapy decreases serum malondialdehyde and neuron-specific enolase and improves Barthel index, indicating hydrogen has additional effects. Registration: URL: https://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000014696.", "conclusion": "Intracisternal magnesium sulfate infusion started immediately after surgery reduces the incidence of cerebral vasospasm and delayed cerebral ischemia and improves clinical outcomes without complications in patients with poor-grade subarachnoid hemorrhage. Intracisternal magnesium sulfate infusion combined with intravenous hydrogen therapy decreases serum malondialdehyde and neuron-specific enolase and improves Barthel index, indicating hydrogen has additional effects. Registration: URL: https://" }, { "pmid": "33454037", "year": 2021, "title": "Heat-retention effects of hydrogen-rich water bath assessed by thermography for humans", "title_en": null, "title_de": "Wärmespeichernde Effekte eines Bades mit wasserstoffreichem Wasser, mittels Thermografie beim Menschen untersucht", "journal": "Journal of Thermal Biology", "authors": "Kato et al.", "author_search": "kato kato", "doi": "10.1016/j.jtherbio.2020.102805", "doi_url": "https://doi.org/10.1016/j.jtherbio.2020.102805", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33454037/", "url": "https://h2medicine.org/studies/study-kato-2021-heat-retention-bath-thermography/", "methods": [ "bath-topical", "drinking-hrw" ], "indications": [ "skin-aging", "cardiovascular", "fundamentals" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2021 · Kato — Heat-retention effects of hydrogen-rich water bath assessed by thermography for humans", "summary": "A hydrogen-rich bath keeps the body warm longer than a normal bath. Thermography on 24 healthy people showed, after identical bathing (41 °C, 10 min), markedly more heat retention — above all in the abdomen, thighs, arms and hands — as well as widened fingertip capillaries as a sign of better circulation. (Journal of Thermal Biology, 2021.)", "assessment": "Directly relevant for H₂ bath/wellness products (the H₂ bath as an application form alongside drinking water and inhalation). The study provides a concrete, everyday and easily communicable argument: noticeably longer warmth + a sign of better circulation. The stated H₂ concentrations (185–548 µg/L) and the strongly negative redox potential (−167 to −91 mV) are useful reference values for product communication. Limitations honestly: small sample (n = 24), only healthy subjects, short follow-up (max. 60 min), and the circulation claim is indirect (capillary thickness/thermography instead of a direct flow measurement). No clinical endpoints. Classification as pilot/mechanistic evidence in a wellness context — no medical cure promise.", "abstract": "Hydrogen-rich water bath devices are commercially available, but have been scarcely clarified for heat-retention effects. In this study, heat-retention effects of hydrogen-rich water bath were assessed by thermographic clinical trials, which employed twenty-four healthy subjects. The thermograms indicated that, under the same conditions (41 °C, 10-min bathing), hydrogen-rich water bath (hydrogen concentrations: 185-548 μg/L; oxidation-reduction potentials: -167 to -91 mV, versus 0.8 μg/L and +479 mV for normal bath, respectively) brought about the heat-retention being more marked than those of normal water bath for several body-parts in the order as follows: abdomen > upper legs > arms > hands > feet, for 30- and 60-min post-bathing, being in contrast to scarce heat-retention for head, armpits and lower legs. Then, as reflection to promotive effects on blood stream, we also examined the thickness of fingertip-capillary in hands. The thickness was expanded in the hydrogen-rich water bath more markedly than that in the normal water bath, suggesting that the hydrogen-rich water bath may have the hydrogen-based promotive effect, exceeding over mere heat retention-based effects, on blood circulation of the whole body. Meanwhile, the heat-retention in hydrogen-rich water bath weakly or moderately correlated with contents of the subcutaneous fat, whole body fat and body mass index, and inversely correlated with skeletal muscle rates, although their correlation degrees did not obviously exceed over normal water bath, with a poor relation with the basal metabolism rate. Thus, the hydrogen-rich water bath was suggested to exert heat-retention effects exceeding over normal water bath, in diverse body-parts such as abdomen, upper legs, arms and hands, via promotion to blood flow which was reflected by expanding the thickness of capillary. The heat-retention after bathing can be noted as effects of the hydrogen-rich water bath, which is applicable for most of people widespread regardless of their body composition index.", "conclusion": "Thus, the hydrogen-rich water bath was suggested to exert heat-retention effects exceeding over normal water bath, in diverse body-parts such as abdomen, upper legs, arms and hands, via promotion to blood flow which was reflected by expanding the thickness of capillary. The heat-retention after bathing can be noted as effects of the hydrogen-rich water bath, which is applicable for most of people " }, { "pmid": "33530211", "year": 2021, "title": "Effects of concomitant use of hydrogen water and photobiomodulation on Parkinson disease: A pilot study", "title_en": null, "title_de": "Auswirkungen der kombinierten Anwendung von Wasserstoffwasser und Photobiomodulation auf die Parkinson-Krankheit: Eine Pilotstudie", "journal": "Medicine", "authors": "Hong et al.", "author_search": "hong hong", "doi": "10.1097/md.0000000000024191", "doi_url": "https://doi.org/10.1097/md.0000000000024191", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33530211/", "url": "https://h2medicine.org/studies/study-hong-2021-photobiomodulation-parkinson-disease/", "methods": [ "drinking-hrw" ], "indications": [ "neurology", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2021 · Hong — Effects of concomitant use of hydrogen water and photobiomodulation on Parkinson disease: A pilot study", "summary": "H₂ water combined with photobiomodulation lowered Parkinson symptom scores — safely and without side effects. In a small proof-of-concept study (18 patients, 2 weeks), UPDRS scores dropped significantly from the very first week and remained better than baseline even one week after the end of therapy. (Medicine, 2021 — pilot study without control group.)", "assessment": "Notable as an example in the neurodegeneration/H₂ field, fitting the mechanistic foundation (H₂ selectively scavenges the most aggressive ROS — Ohsawa 2007). The combination design with light therapy fits the mechanistic picture „H₂ protects against the oxidative price of other therapies“, but it complicates attributing the effect cleanly to H₂ alone. Limitations honestly, and they are considerable: very small sample (n = 18), no control or placebo group, no blinding, short treatment duration (2 weeks), combined intervention (H₂ not isolable), subjective endpoint components. Classified as pilot/proof-of-concept evidence. No promise of cure — Parkinson remains incurable; H₂ is an experimental add-on here.", "abstract": "BACKGROUND: Parkinson disease (PD), the second most common neurodegenerative disease, has no cure or applicable disease-modifying approach, only symptomatic therapy. Oxidative stress and mitochondrial dysfunction play key roles in PD pathophysiology. Animal studies have demonstrated that photobiomodulation (PBM) may enhance mitochondrial function and boost adenosine triphosphate production, thus alleviating PD symptoms; however, this process can cause increased reactive oxygen species (ROS) production. Molecular hydrogen (H2) is a potent and possibly therapeutic antioxidant that can mitigate the effect of ROS. PBM targeting the brainstem may facilitate neuronal activity, and the concomitant H2 may clear additional ROS produced by PBM. Therefore, this study aimed to determine the safety and effectiveness of PBM + H2 in patients with PD. METHODS: We included 18 patients with PD (age 30-80 years) who were at Hoehn and Yahr stages II-III. All the participants received daily PBM + H2 therapy for 2 weeks. The adverse event and the Unified Parkinson Disease Rating Scale (UPDRS) scores were recorded. RESULTS: We noted that the UPDRS scores began significantly decreasing from the first week, and this improvement persisted until the end of therapy. Moreover, no adverse event was recorded. After 1 week of therapy cessation, UPDRS scores slightly increased but the improvement remained significant compared with the baseline. CONCLUSION: This novel, proof-of-concept study demonstrated that PBM+H2 therapy is safe and reduces disease severity. A larger-scaled clinical trial is warranted to completely investigate the effects of PBM + H2 therapy on PD.", "conclusion": "This novel, proof-of-concept study demonstrated that PBM+H2 therapy is safe and reduces disease severity. A larger-scaled clinical trial is warranted to completely investigate the effects of PBM + H2 therapy on PD." }, { "pmid": "33742060", "year": 2021, "title": "Randomized, crossover clinical efficacy trial in humans and mice on tear secretion promotion and lacrimal gland protection by molecular hydrogen", "title_en": null, "title_de": "Randomisierte Crossover-Studie zur klinischen Wirksamkeit an Mensch und Maus zur Förderung der Tränensekretion und zum Schutz der Tränendrüse durch molekularen Wasserstoff", "journal": "Scientific Reports", "authors": "Kubota et al.", "author_search": "kubota kubota", "doi": "10.1038/s41598-021-85895-y", "doi_url": "https://doi.org/10.1038/s41598-021-85895-y", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33742060/", "url": "https://h2medicine.org/studies/study-kubota-2021-tear-secretion-lacrimal-gland/", "methods": [ "drinking-hrw" ], "indications": [ "eye", "oxidative-stress", "skin-aging" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2021 · Kubota — Randomized, crossover clinical efficacy trial in humans and mice on tear secretion promotion and lacrimal gland protection by molecular hydrogen", "summary": "Molecular hydrogen improved tear film stability and dry eye symptoms. In an exploratory crossover trial (10 subjects), an H₂-generating supplement raised the exhaled H₂ concentration and significantly stabilized the tear film (p (Scientific Reports, 2021.)", "assessment": "Interesting because it addresses an unusual but everyday indication (dry eye) with an H₂ drinking supplement and links human and animal data — this strengthens mechanistic plausibility. For us, evidence that H₂ water/supplements are studied beyond the „classic“ fields. Limitation, stated honestly: the human study is a small exploratory pilot group (n = 10), not large-scale placebo double-blind — hence evidence level 2. Hard proof of efficacy is pending; the authors themselves demand larger studies. The animal part is convincing, but animal experimental effects do not automatically transfer 1:1 to humans.", "abstract": "The incidence of dry eye disease is increasing worldwide because of the aging population and increasing use of information technology. Dry eye disease manifests as tear-layer instability and inflammation caused by osmotic hypersensitization in tear fluids; however, to our knowledge, no agent that treats both pathologies simultaneously is available. Molecular hydrogen (H2) is known to be effective against various diseases; therefore, we aimed to elucidate the effects of H2 on tear dynamics and the treatment of dry eye disease. We revealed that administering a persistent H2-generating supplement increased the human exhaled H2 concentration (p < 0.01) and improved tear stability (p < 0.01) and dry eye symptoms (p < 0.05) significantly. Furthermore, H2 significantly increased tear secretion in healthy mice (p < 0.05) and significantly suppressed tear reduction in a murine dry eye model (p = 0.007). H2 significantly and safely improved tear stability and dry eye symptoms in a small exploratory group of 10 human subjects, a subset of whom reported dry eye symptoms prior to treatment. Furthermore, it increased tear secretion rapidly in normal mice. Therefore, H2 may be a safe and effective new treatment for dry eye disease and thus larger trials are warranted.", "conclusion": "Furthermore, it increased tear secretion rapidly in normal mice. Therefore, H2 may be a safe and effective new treatment for dry eye disease and thus larger trials are warranted." }, { "pmid": "33942780", "year": 2021, "title": "Protective effects of hydrogen gas inhalation on radiation-induced bone marrow damage in cancer patients: a retrospective observational study", "title_en": null, "title_de": "Schützende Wirkungen der Wasserstoffgas-Inhalation auf strahleninduzierte Knochenmarkschäden bei Krebspatienten: eine retrospektive Beobachtungsstudie", "journal": "Medical Gas Research", "authors": "Hirano et al.", "author_search": "hirano hirano", "doi": "10.4103/2045-9912.314329", "doi_url": "https://doi.org/10.4103/2045-9912.314329", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33942780/", "url": "https://h2medicine.org/studies/study-hirano-2021-gas-inhalation-radiation-bone-marrow-cancer/", "methods": [ "inhalation" ], "indications": [ "cancer", "oxidative-stress", "immune-system" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2021 · Hirano — Protective effects of hydrogen gas inhalation on radiation-induced bone marrow damage in cancer patients: a retrospective observational study", "summary": "Hydrogen inhalation mitigated bone marrow damage from irradiation — without weakening the tumor effect. In cancer patients undergoing intensity-modulated radiotherapy, 5% H₂ gas significantly limited the drop in white blood cells and platelets (p = 0.0011 and p = 0.0275, respectively). (Medical Gas Research, 2021 — small retrospective observational study.)", "assessment": "Highly relevant for the narrative „H₂ selectively protects healthy tissue“ — here specifically as an adjunct therapy to cancer treatment. The argument „mitigates side effects without weakening the therapy“ is strong because it addresses exactly the concern that an antioxidant might neutralize the radiation effect. Mechanistically it fits Ohsawa 2007 (selective scavenging of hydroxyl radical and peroxynitrite). Limitations honestly: retrospective, very small (n = 16 vs. 7), no randomization, no true placebo control (comparison group received hyperbaric oxygen), differing age distribution. Classified as pilot/observational evidence. Important: no promise of cure — H₂ does not replace oncological therapy but is only studied here as a supportive measure.", "abstract": "Although intensity-modulated radiation therapy (IMRT) has been developed as an alternative to conventional radiotherapy, reducing bone marrow damage is limited. Thus, a novel technology is needed to further mitigate IMRT-induced bone marrow damage. Molecular hydrogen (H2) was recently reported as a preventive and therapeutic antioxidant that selectively scavenges hydroxyl radical (·OH) and peroxynitrite (ONOO-). This observational study aimed to examine whether H2 gas treatment improves IMRT-induced bone marrow damage in cancer patients. The study was performed at Clinic C4 in Tokyo, Japan between May 2015 and November 2016. During this period, all enrolled patients received IMRT once per day for 1 to 4 weeks. After each time of IMRT, the patients of control group (n = 7, 3 men and 4 women, age range: 26-70 years) received mild hyperbaric oxygen therapy in health care chamber for 30 minutes, and the patients of H2 group (n = 16, 8 men and 8 women, age range: 35-82 years) received 5% H2 gas in health care chamber for 30 minutes once per day. Radiation-induced bone marrow damage was evaluated by hematological examination of peripheral blood obtained before and after IMRT, and the data were expressed by the ratio after to before treatment. The total number of radiation times and total exposure doses of radiation were similar between the control and H2 groups. IMRT with health care chamber therapy significantly reduced white blood cells and platelets, but not red blood cells, hemoglobin and hematocrit. In contrast, H2 gas treatment significantly alleviates the reducing effects of white blood cells and platelets (P = 0.0011 and P = 0.0275, respectively). Tumor responses to IMRT were similar between the two groups. The results obtained demonstrated that H2 gas inhalation therapy alleviated IMRT-induced bone marrow damage without compromising the anti-tumor effects of IMRT. The present study suggests that this novel approach of H2 gas inhalation therapy may be applicable to IMRT-induced bone marrow damage in cancer patients. The study protocol was approved by an Ethics Committee Review of Tokyo Clinic and Research Institute ICVS Incorporated (Tokyo, Japan) on February 1, 2019, and was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN ID: UMIN000035864) on February 20, 2019.", "conclusion": "The present study suggests that this novel approach of H2 gas inhalation therapy may be applicable to IMRT-induced bone marrow damage in cancer patients. The study protocol was approved by an Ethics Committee Review of Tokyo Clinic and Research Institute ICVS Incorporated (Tokyo, Japan) on February 1, 2019, and was registered in the University Hospital Medical Information Network (UMIN) Clinical T" }, { "pmid": "34601077", "year": 2021, "title": "The effects of 6-month hydrogen-rich water intake on molecular and phenotypic biomarkers of aging in older adults aged 70 years and over: A randomized controlled pilot trial", "title_en": null, "title_de": "Die Wirkungen einer 6-monatigen Einnahme von wasserstoffreichem Wasser auf molekulare und phänotypische Biomarker des Alterns bei älteren Erwachsenen ab 70 Jahren: Eine randomisierte kontrollierte Pilotstudie", "journal": "Experimental Gerontology", "authors": "Zanini et al.", "author_search": "zanini zanini", "doi": "10.1016/j.exger.2021.111574", "doi_url": "https://doi.org/10.1016/j.exger.2021.111574", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/34601077/", "url": "https://h2medicine.org/studies/study-zanini-2021-6-month-biomarkers-aging-older-adults/", "methods": [ "drinking-hrw" ], "indications": [ "skin-aging", "neurology", "oxidative-stress", "metabolic" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2021 · Zanini — The effects of 6-month hydrogen-rich water intake on molecular and phenotypic biomarkers of aging in older adults aged 70 years and over: A randomized controlled pilot trial", "summary": "6 months of hydrogen water (0.5 L/day, 15 ppm) in 40 people over 70 lengthened the telomeres (a marker of cell aging) and improved brain metabolism as well as leg strength (chair-stand test, P = 0.01) — while telomeres shortened in the control group. (Randomized pilot RCT, Experimental Gerontology, 2021.)", "assessment": "This study is directly relevant for us because it tests exactly the product used in everyday life: hydrogen water for drinking (15 ppm, 0.5 L/day) — and over half a year in a real control group. The telomere and brain data are a strong narrative argument for „healthy aging“. Limitations, stated honestly: it is a pilot RCT with only 40 participants (evidence level 2, not 3) — the authors call it „pilot“ themselves. Many endpoints were not significant (P > 0.05), some P-values lie just under 0.05 (multiple testing increases the risk of chance), and the telomere changes are small. No proof of life extension — rather a promising signal that needs larger studies. Registered under NCT04430803.", "abstract": "In this randomized controlled pilot trial, we investigated the effects of a 6-month intake of hydrogen-rich water (HRW) on several molecular and phenotypic biomarkers of aging in older adults aged 70 years and over. Forty older adults (20 women) were randomly allocated in a parallel-group design to receive 0.5 L per day of HRW (15 ppm of hydrogen) or control drink (0 ppm of hydrogen) during a 6-month intervention period. The biomarkers assessed at baseline and 6-month follow up were molecular markers in the blood (DNA and chromosomes, nutrient sensing, protein, and lipid metabolism, oxidative stress and mitochondria, cell senescence, inflammation), brain metabolism, cognitive functioning, physical function and body composition, resting blood pressure, facial skin features, sleep outcomes, and health-related quality of life. The mean age, weight, and height of study participants were 76.0 ± 5.6 years, 78.2 ± 16.1 kg, height 167.5 ± 11.5 cm, respectively. A significant treatment vs. time interaction was found for telomere length (P = 0.049), with the length increased after HRW intervention (from 0.99 ± 0.15 at baseline to 1.02 ± 0.26 at follow up) and decreased after drinking control water (from 0.92 ± 0.27 to 0.79 ± 0.15). A marker of DNA methylation (Tet methylcytosine dioxygenase 2, TET2) expression at 6-month follow-up increased in both groups, yet the degree of elevation was significantly higher in HRW (from 0.81 ± 0.52 at baseline to 1.62 ± 0.66 at follow up) comparing to the control water (from 1.13 ± 0.82 to 1.76 ± 0.87) (P = 0.040). A strong trend for treatment vs. time interaction was found for a degree of DNA methylation (P = 0.166), with the methylation increased in the HRW group (from 120.6 ± 39.8 ng at baseline to 126.6 ± 33.8 ng at follow up) and decreased after taking control water (from 133.6 ± 52.9 ng to 121.2 ± 38.4 ng). HRW was superior to control water to increase brain choline and NAA levels in the left frontal grey matter, brain creatine at the right parietal white matter, and brain NAA at the right parietal mesial grey matter (P < 0.05). No significant differences were found between interventions for other outcomes (P > 0.05), except for a significantly improved chair stand performance after HRW intervention compared to the control water (P = 0.01). Owing to pleiotropic mechanisms of hydrogen action, this simple biomedical gas could be recognized as a possible anti-aging agent that tackles several hallmarks of aging, including loss of function and telomere length shortening. The study was registered at ClinicalTrials.gov (NCT04430803).", "conclusion": "Owing to pleiotropic mechanisms of hydrogen action, this simple biomedical gas could be recognized as a possible anti-aging agent that tackles several hallmarks of aging, including loss of function and telomere length shortening. The study was registered at ClinicalTrials.gov (NCT04430803)." }, { "pmid": "35046230", "year": 2021, "title": "[ASSOCIATION OF BREATH HYDROGEN CONCENTRATION WITH ORAL INTAKE AND URINARY DISEASES].", "title_en": null, "title_de": "Zusammenhang der Wasserstoffkonzentration in der Atemluft mit oraler Nahrungsaufnahme und Harnwegserkrankungen", "journal": "Nihon Hinyokika Gakkai zasshi. The japanese journal of urology", "authors": "Sugaya et al.", "author_search": "sugaya sugaya", "doi": "10.5980/jpnjurol.112.11", "doi_url": "https://doi.org/10.5980/jpnjurol.112.11", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/35046230/", "url": "https://h2medicine.org/studies/study-sugaya-2021-association-breath-concentration-oral/", "methods": [], "indications": [ "skin-aging", "fundamentals-safety" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "breath-test", "headline": "2021 · Sugaya — Association of Breath Hydrogen Concentration with Oral Intake and Urinary Diseases", "summary": "Breath hydrogen levels rise temporarily after eating, drinking — including hydrogen water — and with age in women, but are not associated with benign prostatic hyperplasia, overactive bladder, or constipation. Individual variation in breath H₂ is enormous (0.4–188.6 ppm), driven primarily by differences in gut flora rather than therapy. (Nihon Hinyokika Gakkai Zasshi, 2021.)", "assessment": "A useful physiological characterisation study rather than a therapeutic efficacy trial. Its value lies in understanding H₂ pharmacokinetics: gut flora, not supplemental H₂ intake, dominates breath H₂ levels; and individual variability is enormous. Limitations: small sample (85 healthy volunteers, 70 urological patients), not all measurement conditions were standardised, and breath H₂ as a proxy for blood or tissue H₂ bioavailability remains uncertain. The null findings for urological conditions are honest and informative — but this study was never designed to test therapeutic H₂ effects on those conditions.", "abstract": "(Purpose) Ingestion of hydrogen is said to prevent oxidation in the body, but hydrogen is produced by intestinal bacterial flora and excreted in the exhaled breath. We investigated how breath hydrogen concentrations change with the diurnal cycle and under various conditions, including after consuming food or drink, and in people with urological disease. (Subjects and methods) Participants were healthy volunteers (40 men, 45 women; 30-83 years old) and urological outpatients (40 men with benign prostatic hyperplasia, 30 women with overactive bladder; 60 years or older). Breath hydrogen levels were measured before and after eating and drinking in three volunteers, and its diurnal variation was examined in one. The relationship between breath hydrogen and age or urological disease status was also analyzed by gender. Additional measurements were taken in the person with the highest breath hydrogen concentration and the person with the lowest; in these two people, breath hydrogen was measured at the same time for 10 or more days to determine the fluctuation range. (Results) Breath hydrogen concentration increased temporarily after ingestion of tap water, hydrogen water or food. It also increased with food intake and in cases of flatulence with intestinal gas accumulation, but decreased after defecation. In the person with the highest breath hydrogen, concentrations were 11.2-188.6 ppm, whereas in the person with the lowest, they were 0.4-2.3 ppm. Breath hydrogen increased significantly with age in healthy female volunteers. There was no association between breath hydrogen and benign prostatic hyperplasia, overactive bladder or constipation. (Conclusion) Breath hydrogen concentration increases with eating, drinking and aging, and is not associated with benign prostatic hyperplasia, overactive bladder or constipation. Breath hydrogen concentration varies widely between individuals, which may be due to differences in intestinal flora.", "conclusion": ") Breath hydrogen concentration increases with eating, drinking and aging, and is not associated with benign prostatic hyperplasia, overactive bladder or constipation. Breath hydrogen concentration varies widely between individuals, which may be due to differences in intestinal flora." }, { "pmid": "34830187", "year": 2021, "title": "Ammonium Formate-Pd/C as a New Reducing System for 1,2,4-Oxadiazoles. Synthesis of Guanidine Derivatives and Reductive Rearrangement to Quinazolin-4-Ones with Potential Anti-Diabetic Activity.", "title_en": null, "title_de": "Ammoniumformiat-Pd/C als neues Reduktionssystem für 1,2,4-Oxadiazole: Synthese von Guanidin-Derivaten und reduktive Umlagerung zu Chinazolin-4-onen mit potenzieller antidiabetischer Aktivität", "journal": "International journal of molecular sciences", "authors": "Marzullo et al.", "author_search": "marzullo marzullo", "doi": "10.3390/ijms222212301", "doi_url": "https://doi.org/10.3390/ijms222212301", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/34830187/", "url": "https://h2medicine.org/studies/study-marzullo-2021-ammonium-formate-reducing-system/", "methods": [ "unspecified" ], "indications": [ "diabetes", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2021 · Marzullo et al. — Ammonium Formate-Pd/C as a New Reducing System for 1,2,4-Oxadiazoles: Synthesis of Guanidine Derivatives and Reductive Rearrangement to Quinazolin-4-Ones with Potential Anti-Diabetic Activity", "summary": "This is an organic chemistry study describing a new laboratory synthesis method for heterocyclic compounds with potential anti-diabetic activity. Molecular hydrogen (H₂) is used here exclusively as a chemical reagent in the synthesis process — not as a therapeutic agent. The study has no direct relevance to hydrogen water, H₂ inhalation therapy, or biomedical hydrogen applications.", "assessment": "This paper is not relevant to biomedical hydrogen therapy. Molecular hydrogen is used solely as a reducing agent in organic chemistry synthesis. The biological testing is preliminary and in-vitro only. There are no findings regarding therapeutic hydrogen (hydrogen water, H₂ inhalation) and no implications for human health applications of molecular hydrogen. This study should not be cited as evidence for any H₂ health benefit.", "abstract": "1,2,4-Oxadiazole is a heterocycle with wide reactivity and many useful applications. The reactive O-N bond is usually reduced using molecular hydrogen to obtain amidine derivatives. NH4CO2H-Pd/C is here demonstrated as a new system for the O-N reduction, allowing us to obtain differently substituted acylamidine, acylguanidine and diacylguanidine derivatives. The proposed system is also effective for the achievement of a reductive rearrangement of 5-(2'-aminophenyl)-1,2,4-oxadiazoles into 1-alkylquinazolin-4(1H)-ones. The alkaloid glycosine was also obtained with this method. The obtained compounds were preliminarily tested for their biological activity in terms of their cytotoxicity, induced oxidative stress, α-glucosidase and DPP4 inhibition, showing potential application as anti-diabetics.", "conclusion": "The alkaloid glycosine was also obtained with this method. The obtained compounds were preliminarily tested for their biological activity in terms of their cytotoxicity, induced oxidative stress, α-glucosidase and DPP4 inhibition, showing potential application as anti-diabetics." }, { "pmid": "34781966", "year": 2021, "title": "Hydrogen gas with extracorporeal cardiopulmonary resuscitation improves survival after prolonged cardiac arrest in rats.", "title_en": null, "title_de": "Wasserstoffgas in Kombination mit extrakorporaler kardiopulmonaler Reanimation verbessert das Überleben nach längerem Herzstillstand bei Ratten", "journal": "Journal of translational medicine", "authors": "Yin et al.", "author_search": "yin yin", "doi": "10.1186/s12967-021-03129-1", "doi_url": "https://doi.org/10.1186/s12967-021-03129-1", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/34781966/", "url": "https://h2medicine.org/studies/study-yin-2021-extracorporeal-cardiopulmonary-resuscitation-improves/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "sports-exercise", "neurology", "cardiovascular", "cancer", "respiratory", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2021 · Yin et al. — Hydrogen Gas with Extracorporeal Cardiopulmonary Resuscitation Improves Survival after Prolonged Cardiac Arrest in Rats", "summary": "In a rat model of prolonged cardiac arrest, adding hydrogen gas (H₂) to extracorporeal cardiopulmonary resuscitation (ECPR) dramatically improved 4-hour survival: 78% with H₂ versus 22% without. H₂ also restored brain electrical activity, protected blood vessel lining, and reduced inflammatory damage. This is a preclinical animal study — the findings cannot be directly transferred to humans without further clinical validation.", "assessment": "This is a well-designed preclinical study with a compelling effect size in a high-mortality model. The mechanistic explanations are consistent with established H₂ biology (oxidative stress reduction, endothelial protection). Critical limitations: this is a rat study with only 9 animals per group and a 4-hour endpoint — far from clinical practice. Asphyxial cardiac arrest in rats does not replicate the heterogeneity of human cardiac arrest patients. ECMO/ECPR studies in humans already face enormous complexity. This paper contributes meaningful preclinical groundwork but does not constitute evidence of efficacy in humans.", "abstract": "BACKGROUND: Despite the benefits of extracorporeal cardiopulmonary resuscitation (ECPR) in cohorts of selected patients with cardiac arrest (CA), extracorporeal membrane oxygenation (ECMO) includes an artificial oxygenation membrane and circuits that contact the circulating blood and induce excessive oxidative stress and inflammatory responses, resulting in coagulopathy and endothelial cell damage. There is currently no pharmacological treatment that has been proven to improve outcomes after CA/ECPR. We aimed to test the hypothesis that administration of hydrogen gas (H2) combined with ECPR could improve outcomes after CA/ECPR in rats. METHODS: Rats were subjected to 20 min of asphyxial CA and were resuscitated by ECPR. Mechanical ventilation (MV) was initiated at the beginning of ECPR. Animals were randomly assigned to the placebo or H2 gas treatment groups. The supplement gas was administered with O2 through the ECMO membrane and MV. Survival time, electroencephalography (EEG), brain functional status, and brain tissue oxygenation were measured. Changes in the plasma levels of syndecan-1 (a marker of endothelial damage), multiple cytokines, chemokines, and metabolites were also evaluated. RESULTS: The survival rate at 4 h was 77.8% (7 out of 9) in the H2 group and 22.2% (2 out of 9) in the placebo group. The Kaplan-Meier analysis showed that H2 significantly improved the 4 h-survival endpoint (log-rank P = 0.025 vs. placebo). All animals treated with H2 regained EEG activity, whereas no recovery was observed in animals treated with placebo. H2 therapy markedly improved intra-resuscitation brain tissue oxygenation and prevented an increase in central venous pressure after ECPR. H2 attenuated an increase in syndecan-1 levels and enhanced an increase in interleukin-10, vascular endothelial growth factor, and leptin levels after ECPR. Metabolomics analysis identified significant changes at 2 h after CA/ECPR between the two groups, particularly in D-glutamine and D-glutamate metabolism. CONCLUSIONS: H2 therapy improved mortality in highly lethal CA rats rescued by ECPR and helped recover brain electrical activity. The underlying mechanism might be linked to protective effects against endothelial damage. Further studies are warranted to elucidate the mechanisms responsible for the beneficial effects of H2 on ischemia-reperfusion injury in critically ill patients who require ECMO support.", "conclusion": "H2 therapy improved mortality in highly lethal CA rats rescued by ECPR and helped recover brain electrical activity. The underlying mechanism might be linked to protective effects against endothelial damage. Further studies are warranted to elucidate the mechanisms responsible for the beneficial effects of H2 on ischemia-reperfusion injury in critically ill patients who require ECMO support." }, { "pmid": "34674744", "year": 2021, "title": "Effect of hydrogen gas inhalation on patient QOL after hepatectomy: protocol for a randomized controlled trial.", "title_en": null, "title_de": "Wirkung der Inhalation von Wasserstoffgas auf die Lebensqualität von Patienten nach Hepatektomie: Protokoll für eine randomisierte kontrollierte Studie", "journal": "Trials", "authors": "Kaibori et al.", "author_search": "kaibori kaibori", "doi": "10.1186/s13063-021-05697-5", "doi_url": "https://doi.org/10.1186/s13063-021-05697-5", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/34674744/", "url": "https://h2medicine.org/studies/study-kaibori-2021-inhalation-qol-after-hepatectomy/", "methods": [ "inhalation" ], "indications": [ "liver", "sports-exercise", "immune-system", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2021 · Kaibori — Effect of hydrogen gas inhalation on patient QOL after hepatectomy: protocol for a randomised controlled trial", "summary": "This is a published trial protocol — not yet results — for a randomised, double-blind, controlled study testing whether inhaling hydrogen gas after liver surgery improves patients' quality of life and reduces post-operative complications. The trial was registered and approved in Japan as a specified clinical trial under the Clinical Trials Act. (Trials, 2021.)", "assessment": "This is a protocol paper only — no results can be assessed. Its value is in demonstrating that a properly designed, pre-registered, double-blind RCT of H₂ inhalation post-hepatectomy was underway. The mechanistic rationale (H₂ neutralising ischaemia-reperfusion ROS) is well-supported by animal data cited in the introduction. Important caveats: until results are published, no conclusion about efficacy can be drawn; the QoR-40 on day 3 is a validated but subjective endpoint; and post-operative H₂ delivery requires specialised equipment not universally available.", "abstract": "INTRODUCTION: Molecular hydrogen had been considered inactive in vivo but is an antioxidant that selectively reduces highly toxic reactive oxygen species (ROS). Animal studies have reported that hydrogen gas inhalation helped alleviate cerebral and cardiac ischemia-reperfusion injuries. In humans, hydrogen inhalation therapy is presently approved as a treatment under Advanced Medical Care B in Japan (jRCTs031180352: limited to adult patients who suffered out-of-hospital cardiac arrest and are in a continuous coma) and its effectiveness is being examined in a clinical trial. The Japanese government has introduced the \"Advanced Medical Care System\" to promote the development of drugs and devices under governmental regulations. Advanced Medical Care B is a system designed for unapproved or off-label drugs or medical technologies used in a clinical trial setting. Hepatectomy is generally performed with repeated hepatic blood-flow occlusion and then reperfusion (ischemia and reperfusion). No report, however, has been made on ROS inhibition by hydrogen inhalation therapy or its effectiveness in post-hepatectomy patients. Hydrogen gas inhalation in the early stages after hepatectomy is anticipated to inhibit liver dysfunction by inhibiting ROS. METHODS AND ANALYSIS: This study is a randomized, controlled, double-blind superiority trial, which will be conducted as a \"specified clinical trial\" in accordance with the Clinical Trials Act in Japan. Trial registration was prospectively completed before the first participant was enrolled. The subjects will be patients who will undergo hepatectomy and will be allocated randomly into group A with hydrogen gas inhalation or group B with air inhalation after hepatectomy. The study will examine if hydrogen gas inhalation improves QOL of post-hepatectomy patients. The primary endpoint is patient QOL (score of a 40-item quality of recovery questionnaire, QoR40) on postoperative day 3 and the secondary endpoints are QoR40s besides that on postoperative day 3, grade of postoperative complications (Clavien-Dindo score), level of pain (Numerical Rating Scale (NRS)), amount of dietary intake, liver function, inflammation level, 8-hydroxydeoxyguanosine (urinary 8-OHdG) level, and number of pedometer-assessed steps. ETHICS AND DISSEMINATION: The study protocol has been approved by the Niigata University Central Review Board of Clinical Research. The findings of this study will be widely disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION: jRCTs 03220332 . Registered on 21 January 2021.", "conclusion": "TRIAL REGISTRATION: jRCTs 03220332 . Registered on 21 January 2021." }, { "pmid": "34645100", "year": 2021, "title": "An H2-infused, nitric oxide-producing functional beverage as a neuroprotective agent for TBIs and concussions.", "title_en": null, "title_de": "Ein H₂-angereichertes, Stickstoffmonoxid-produzierendes funktionelles Getränk als neuroprotektives Mittel bei Schädel-Hirn-Traumata und Gehirnerschütterungen", "journal": "Journal of integrative neuroscience", "authors": "LeBaron et al.", "author_search": "lebaron le baron", "doi": "10.31083/j.jin2003071", "doi_url": "https://doi.org/10.31083/j.jin2003071", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/34645100/", "url": "https://h2medicine.org/studies/study-lebaron-2021-infused-nitric-oxide-producing/", "methods": [ "drinking-hrw" ], "indications": [ "liver", "sports-exercise", "neurology", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2021 · LeBaron et al. — An H₂-Infused, Nitric Oxide-Producing Functional Beverage as a Neuroprotective Agent for TBIs and Concussions", "summary": "Traumatic brain injuries (TBIs) and concussions currently lack effective medical treatments, and this paper argues that a combination of molecular hydrogen and nitric oxide — delivered via a functional beverage — could address multiple aspects of TBI pathophysiology simultaneously. This is an in-vitro/theoretical paper presenting a scientific rationale; no controlled clinical trial was conducted. The beverage discussed is a specific product, but the science reviewed covers general H₂ and nitric oxide biology.", "assessment": "The mechanistic review of H₂ and nitric oxide in TBI context is scientifically well-grounded and draws on a substantial body of literature on H₂ neuroprotection in cell and animal models. Honest limitations: this is an in-vitro/theoretical paper presenting a hypothesis; no randomized clinical trial data on H₂ or this specific beverage in human TBI patients is available. The preliminary indications cited are not from peer-reviewed controlled trials. LeBaron has known conflicts of interest in the hydrogen beverage space. This paper should be read as a biologically motivated hypothesis, not as clinical evidence for TBI treatment.", "abstract": "Traumatic brain injuries (TBIs) are a leading cause of death and disability. Sports-related TBIs are estimated to be more than several million per year. The pathophysiology of TBIs involves high levels of inflammation, oxidative stress, dysregulation of ion homeostasis, mitochondrial dysfunction, and apoptosis. There is also a reduction in cerebral blood flow, leading to hypoxia and reduced removal of metabolic waste, which further exacerbates the injury. There is currently no recognized effective medical treatment or intervention for TBIs, which may in part be due to the difficulty of drug delivery through the blood-brain barrier. Molecular hydrogen has recently emerged as a neuroprotective medical gas against cerebral infarction and neurodegenerative diseases including TBIs. Its small molecular size and nonpolar nature allow it to easily diffuse through the blood-brain barrier, cell membranes and subcellular compartments. Hydrogen has been shown to exert selective anti-inflammatory, antioxidant, and anti-apoptotic effects by regulating various transcription factors and protein phosphorylation cascades. Nitric oxide is another well-recognized medical gas that plays divergent roles in protecting from and in the recovery of TBIs, as well as in contributing to their pathophysiology and injury. Excessive activation of inducible nitric oxide synthase leads to excess inflammation and oxidative/nitrosative damage as well as a paradoxical nitric oxide depletion in the locations it is needed. Hydrogen regulates nitric oxide production and metabolism, which enhances its benefits while reducing its harms. A novel H2-infused, nitric oxide producing beverage, Hydro Shot, may have important neuroprotective benefits for TBIs. We report preliminary indications that Hydro Shot may be a meaningful adjuvant treatment for TBIs.", "conclusion": "A novel H2-infused, nitric oxide producing beverage, Hydro Shot, may have important neuroprotective benefits for TBIs. We report preliminary indications that Hydro Shot may be a meaningful adjuvant treatment for TBIs." }, { "pmid": "34585957", "year": 2021, "title": "Reply to \"Discussion: Drinking hydrogen water enhances endurance and relieves psychometric fatigue: a randomized, double-blind, placebo-controlled study\".", "title_en": null, "title_de": "Erwiderung auf „Diskussion: Das Trinken von Wasserstoffwasser steigert die Ausdauer und lindert psychometrische Erschöpfung: eine randomisierte, doppelblinde, placebokontrollierte Studie”", "journal": "Canadian journal of physiology and pharmacology", "authors": "Ohta et al.", "author_search": "ohta ohta", "doi": "10.1139/cjpp-2021-0151", "doi_url": "https://doi.org/10.1139/cjpp-2021-0151", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/34585957/", "url": "https://h2medicine.org/studies/study-ohta-2021-reply-discussion-drinking-enhances/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2021 · Ohta et al. — Reply to „Discussion: Drinking Hydrogen Water Enhances Endurance and Relieves Psychometric Fatigue: A Randomized, Double-Blind, Placebo-Controlled Study”", "summary": "This is a short reply letter published in the Canadian Journal of Physiology and Pharmacology, responding to a discussion of a hydrogen water endurance study. No abstract is available for this correspondence. For the underlying study on hydrogen water and athletic endurance, see the cited original research. For context on the discussion being replied to, see PMID 34585956.", "assessment": "This is a reply letter, not a primary study or review. No abstract is available via PubMed. The scientific content cannot be assessed without the full text. This entry is included for completeness of the literature record. For the original controlled trial on hydrogen water and endurance, readers should seek the primary publication. See DOI: 10.1139/cjpp-2021-0151.", "abstract": null, "conclusion": null }, { "pmid": "34585956", "year": 2021, "title": "Discussion: Drinking hydrogen water enhances endurance and relieves psychometric fatigue: a randomized, double-blind, placebo-controlled study.", "title_en": null, "title_de": "Diskussion: Das Trinken von Wasserstoffwasser steigert die Ausdauer und lindert psychometrische Erschöpfung: eine randomisierte, doppelblinde, placebokontrollierte Studie", "journal": "Canadian journal of physiology and pharmacology", "authors": "Falster et al.", "author_search": "falster falster", "doi": "10.1139/cjpp-2021-0031", "doi_url": "https://doi.org/10.1139/cjpp-2021-0031", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/34585956/", "url": "https://h2medicine.org/studies/study-falster-2021-discussion-drinking-enhances-endurance/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2021 · Falster et al. — Discussion: Drinking Hydrogen Water Enhances Endurance and Relieves Psychometric Fatigue: A Randomized, Double-Blind, Placebo-Controlled Study", "summary": "This is a published discussion letter commenting on a controlled trial of hydrogen water and athletic endurance. No abstract is available for this correspondence. The letter represents scientific peer commentary on an existing study — it is not itself an original study or systematic review.", "assessment": "This is a discussion letter, not a primary study or review. No abstract is publicly available via PubMed. The content cannot be evaluated without the full text. This entry is included for completeness. For the underlying evidence on hydrogen water and athletic endurance, readers should seek the primary randomized controlled trial. See DOI: 10.1139/cjpp-2021-0031.", "abstract": null, "conclusion": null }, { "pmid": "34524338", "year": 2021, "title": "In situ hydrogen nanogenerator for bimodal imaging guided synergistic photothermal/hydrogen therapies.", "title_en": null, "title_de": "In-situ-Wasserstoff-Nanogenerator für bimodal bildgebungsgeführte synergistische photothermische/Wasserstoff-Therapien", "journal": "Nanoscale", "authors": "Yuan et al.", "author_search": "yuan yuan", "doi": "10.1039/d1nr03260g", "doi_url": "https://doi.org/10.1039/d1nr03260g", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/34524338/", "url": "https://h2medicine.org/studies/study-yuan-2021-situ-nanogenerator-bimodal-imaging/", "methods": [ "inhalation" ], "indications": [ "cancer", "skin-aging" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2021 · Yuan et al. — In Situ Hydrogen Nanogenerator for Bimodal Imaging Guided Synergistic Photothermal/Hydrogen Therapies", "summary": "This nanotechnology study developed a nanoparticle system that generates hydrogen gas locally within tumors, combining hydrogen therapy with photothermal therapy (heat-based cancer treatment) to kill cancer cells. Tests were conducted in cell cultures and in mice — this is a preclinical study with no human data. The approach is innovative at the research level but remains far from clinical application.", "assessment": "This is an inventive preclinical nanotechnology study demonstrating proof-of-concept for tumor-targeted H₂ delivery combined with photothermal therapy in cell culture and mouse models. The mechanistic integration of H₂ therapy, photothermal ablation, and imaging guidance is scientifically innovative. Critical limitations: all efficacy data is from cell lines and mouse tumor xenografts; clinical translation of injectable nanoparticle systems is notoriously complex and lengthy. This study has no relevance to hydrogen water or inhaled H₂; it represents a completely different delivery paradigm. The results cannot be extrapolated to any currently available consumer H₂ product.", "abstract": "Multifunctional nanoagents integrating multiple therapeutic and imaging functions hold promise in the field of non-invasive and precise tumor therapies. However, the complex preparation process and uncertain drug metabolism of nanoagents loaded with various therapeutic agents or imaging agents greatly hinder its clinical applications. Developing simple and effective nanoagents that integrate multiple therapeutic and imaging functions remain a huge challenge. Therefore, a novel strategy based on in situ hydrogen release is proposed in this work: aminoborane (AB) was loaded onto mesoporous polydopamine nanoparticles (MPDA NPs) as a prodrug for hydrogen production, and then, PEG was modified on the surface of nanoparticles (represented as AB@MPDA-PEG). MPDA NPs not only act as photothermal agents (PTA) with high photothermal conversion efficiency (808 nm, η = 38.72%) but also as the carriers of AB accumulated in the tumor through enhanced permeability and retention (EPR) effect. H2 gas generated by AB in the weak acid conditions of the tumor microenvironment (TME) not only was used to treat tumors via a combination of hydrogen and photothermal therapies but also serves as a US and CT contrast agent, providing accurate guidance for tumor treatment. Finally, in vivo and in vitro investigation suggest that the designed multifunctional nanosystem not only showed excellent properties such as high hydrogen-loading capacity, long-lasting sustained hydrogen release ability and excellent biocompatibility but also achieve selective PTT/hydrogen therapies and US/CT bimodal imaging functions, which can effectively guide antitumor therapies. The proposed hydrogen gas-based strategy for combination therapies and bimodal imaging integration holds promise as an efficient and safe tumor treatment for future clinical translation.", "conclusion": "Finally, in vivo and in vitro investigation suggest that the designed multifunctional nanosystem not only showed excellent properties such as high hydrogen-loading capacity, long-lasting sustained hydrogen release ability and excellent biocompatibility but also achieve selective PTT/hydrogen therapies and US/CT bimodal imaging functions, which can effectively guide antitumor therapies. The propose" }, { "pmid": "34513069", "year": 2021, "title": "Application of Molecular Hydrogen in Heart Surgery under Cardiopulmonary Bypass.", "title_en": null, "title_de": "Anwendung von molekularem Wasserstoff in der Herzchirurgie unter Einsatz der Herz-Lungen-Maschine", "journal": "Sovremennye tekhnologii v meditsine", "authors": "Danilova et al.", "author_search": "danilova danilova", "doi": "10.17691/stm2021.13.1.09", "doi_url": "https://doi.org/10.17691/stm2021.13.1.09", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/34513069/", "url": "https://h2medicine.org/studies/study-danilova-2021-application-heart-surgery-under/", "methods": [ "inhalation" ], "indications": [ "metabolic", "cardiovascular", "respiratory", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2021 · Danilova — Application of Molecular Hydrogen in Heart Surgery under Cardiopulmonary Bypass", "summary": "During open-heart surgery on cardiopulmonary bypass, inhaling 1.5–2% hydrogen gas during anaesthesia reduced markers of lipid peroxidation (oxidative stress) compared to patients who did not receive H₂. The effect was most pronounced one day after surgery, suggesting a protective role against ischaemia-reperfusion injury. (Sovremennye Tekhnologii v Meditsine, 2021.)", "assessment": "A small but mechanistically coherent pilot study in a high-stakes clinical setting. The four-timepoint sampling design provides useful kinetic data on oxidative stress evolution during and after CPB. Limitations: n=11/9 per group is too small for clinical conclusions; no clinical outcomes (mortality, ICU stay, organ function) were measured — only biochemical oxidative stress markers; the journal (Russian specialty journal) has limited indexing and peer-review transparency; no blinding of patients or laboratory personnel is described. As a safety-and-signal study, it supports proceeding to a larger RCT with hard clinical endpoints.", "abstract": "UNLABELLED: The aim of this work was to study the effect of molecular hydrogen on oxidative processes in cardiac surgery patients with acquired valve heart disease applied during surgery under cardiopulmonary bypass (CPB). MATERIALS AND METHODS: The study involved 20 patients (16 men and 4 women) with acquired heart valve disease who were operated on under CPB. Two groups of patients were formed. In group 1 (n=11), anesthesia included inhalations of molecular hydrogen, which was supplied to the breathing circuit of the ventilator at a concentration of 1.5-2.0% immediately after tracheal intubation and throughout the operation. In group 2 (n=9), inhalation of molecular hydrogen was not performed. Blood sampling was taken at 4 stages: immediately after anesthesia induction, before CPB and after its termination, and also one day after the operation. The intensity of the processes of lipid peroxidation was evaluated by the level of diene (DC) and triene (TC) conjugates, Schiff bases (SB). RESULTS: In the patients of group 1, the arterial blood samples showed a decrease in the level of TC and SB, as compared to the first stage of the study, before the initiation of CPB and one day after the operation. An increase in the level of DC and TC was detected after the termination of CPB (p<0.05). In the venous blood samples, an increase in the level of DC was noted before the initiation of CPB, which was restored by the third stage of the study (p<0.05). At the same time, after the termination of CPB, a tendency towards a decrease in TC and SB was observed, which persisted one day after the operation.In the patients of group 2, an increase in the concentration of SB in the arterial blood samples was recorded during the study as compared to the first stage. The level of TC and SB in the venous blood samples increased one day after the operation. CONCLUSION: Intraoperative inhalation of molecular hydrogen leads to a decrease in the oxidative stress manifestation, it being most pronounced one day after the operation. This suggests that molecular hydrogen can be used in cardiac surgery as an effective and safe antioxidant.", "conclusion": "Intraoperative inhalation of molecular hydrogen leads to a decrease in the oxidative stress manifestation, it being most pronounced one day after the operation. This suggests that molecular hydrogen can be used in cardiac surgery as an effective and safe antioxidant." }, { "pmid": "34426524", "year": 2021, "title": "H2 in Antarctic firn air: Atmospheric reconstructions and implications for anthropogenic emissions.", "title_en": null, "title_de": "H₂ in antarktischer Firnluft: Atmosphärische Rekonstruktionen und Implikationen für anthropogene Emissionen", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "authors": "Patterson et al.", "author_search": "patterson patterson", "doi": "10.1073/pnas.2103335118", "doi_url": "https://doi.org/10.1073/pnas.2103335118", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/34426524/", "url": "https://h2medicine.org/studies/study-patterson-2021-antarctic-firn-air-atmospheric/", "methods": [ "unspecified" ], "indications": [ "cardiovascular" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2021 · Patterson et al. — H₂ in Antarctic Firn Air: Atmospheric Reconstructions and Implications for Anthropogenic Emissions", "summary": "This is an atmospheric science study — it investigates how levels of molecular hydrogen (H₂) in the Earth's atmosphere have changed from 1852 to 2003, using ancient air trapped in Antarctic snow layers. This study has no relevance to biomedical hydrogen therapy. Molecular hydrogen here is an atmospheric trace gas studied for environmental and climate science purposes.", "assessment": "This paper is not relevant to biomedical hydrogen therapy. It is atmospheric chemistry and climate science. The molecular hydrogen (H₂) studied here is an atmospheric trace gas at parts-per-billion concentrations in Antarctic ice cores — an entirely different context from therapeutic H₂ at dissolved millimolar concentrations or inhaled at percent-level concentrations. This study provides no evidence for or against any health effect of hydrogen. It is included here for completeness of the literature search.", "abstract": "The atmospheric history of molecular hydrogen (H2) from 1852 to 2003 was reconstructed from measurements of firn air collected at Megadunes, Antarctica. The reconstruction shows that H2 levels in the southern hemisphere were roughly constant near 330 parts per billion (ppb; nmol H2 mol-1 air) during the mid to late 1800s. Over the twentieth century, H2 levels rose by about 70% to 550 ppb. The reconstruction shows good agreement with the H2 atmospheric history based on firn air measurements from the South Pole. The broad trends in atmospheric H2 over the twentieth century can be explained by increased methane oxidation and anthropogenic emissions. The H2 rise shows no evidence of deceleration during the last quarter of the twentieth century despite an expected reduction in automotive emissions following more stringent regulations. During the late twentieth century, atmospheric CO levels decreased due to a reduction in automotive emissions. It is surprising that atmospheric H2 did not respond similarly as automotive exhaust is thought to be the dominant source of anthropogenic H2. The monotonic late twentieth century rise in H2 levels is consistent with late twentieth-century flask air measurements from high southern latitudes. An additional unknown source of H2 is needed to explain twentieth-century trends in atmospheric H2 and to resolve the discrepancy between bottom-up and top-down estimates of the anthropogenic source term. The firn air-based atmospheric history of H2 provides a baseline from which to assess human impact on the H2 cycle over the last 150 y and validate models that will be used to project future trends in atmospheric composition as H2 becomes a more common energy source.", "conclusion": "An additional unknown source of H2 is needed to explain twentieth-century trends in atmospheric H2 and to resolve the discrepancy between bottom-up and top-down estimates of the anthropogenic source term. The firn air-based atmospheric history of H2 provides a baseline from which to assess human impact on the H2 cycle over the last 150 y and validate models that will be used to project future tren" }, { "pmid": "34328487", "year": 2021, "title": "A PdMo bimetallene with precise wavelength adjustment and catalysis for synergistic photothermal ablation and hydrogen therapy of cancer at different depths.", "title_en": null, "title_de": "Ein PdMo-Bimetallen mit präziser Wellenlängenanpassung und Katalyse für synergistische photothermische Ablation und Wasserstofftherapie von Krebs in unterschiedlichen Tiefen", "journal": "Journal of materials chemistry. B", "authors": "Bai et al.", "author_search": "bai bai", "doi": "10.1039/d1tb01284c", "doi_url": "https://doi.org/10.1039/d1tb01284c", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/34328487/", "url": "https://h2medicine.org/studies/study-bai-2021-pdmo-bimetallene-precise-wavelength/", "methods": [ "unspecified" ], "indications": [ "liver", "cancer", "fundamentals-safety" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2021 · Bai et al. — A PdMo Bimetallene with Precise Wavelength Adjustment and Catalysis for Synergistic Photothermal Ablation and Hydrogen Therapy of Cancer at Different Depths", "summary": "This nanotechnology study synthesized a novel palladium-molybdenum (PdMo) bimetallene nanomaterial that simultaneously generates hydrogen gas and produces heat under near-infrared light, enabling combined anti-tumor therapy in mouse models. This is an in-vitro and in-vivo preclinical study — no human data. The approach represents advanced nanomaterial research, not a clinical therapy.", "assessment": "This is an innovative preclinical materials science study demonstrating proof-of-concept for a dual photothermal/hydrogen nano-oncology platform. The NIR tunability and tumor-depth versatility are genuine technical advances. Critical limitations: all data is from cell cultures and mouse tumor models; clinical translation of injectable bimetallic nanomaterials involves extensive regulatory and safety evaluation that does not yet exist for this system. The H₂ is delivered via nanomaterial-mediated in-situ generation — entirely unrelated to hydrogen water, H₂ inhalation, or any current consumer product. This study does not constitute evidence for hydrogen therapy in humans.", "abstract": "By delivering the idea of green and safe hydrogen energy and novel photothermal therapy to the biomedical field, engineering of therapeutic nanomaterials for treatment of major diseases (such as cancer) holds great significance. In this work, a novel PdMo bimetallene was synthesized by a solvothermal reduction method, and it was explored and applied in the field of anti-tumor therapy for the first time. The absorption peak of the PdMo bimetallene can be precisely adjusted in the NIR biological window (700-1350 nm) only by changing the synthesis time. At the same time, it also shows strong light absorption and high photothermal conversion efficiency. Specifically, the photothermal conversion efficiencies at 808 nm, 980 nm and 1064 nm are 43.1%, 51.7% and 69.15%, respectively. Surprisingly, a PdMo bimetallene is an efficient catalyst, which can effectively promote hydrogen production from the hydrolysis of ammonia borane (AB) under acidic and photothermal conditions. Benefitting from these excellent properties, a multifunctional composite nano therapeutic agent (PdMo@AB@HA) was developed via layer-by-layer surface modification with AB and hyaluronic acid (HA). In this way, the synergistic PTT/hydrogen therapy of PdMo@AB@HA composite nanosheets in the NIR-I and NIR-II windows (808 nm, 980 nm, and 1064 nm) on mouse tumor xenografts of different depths was realized. Furthermore, the controlled release of hydrogen, targeted endocytosis, efficient eradication of tumors of different depths and high biosafety were systematically proved in vitro and in vivo. This work not only provides a novel and efficient theranostic nanoplatform for efficient cancer theranostics, but also provides a new strategy for the development of safe and efficient new anti-tumor therapies.", "conclusion": "Furthermore, the controlled release of hydrogen, targeted endocytosis, efficient eradication of tumors of different depths and high biosafety were systematically proved in vitro and in vivo. This work not only provides a novel and efficient theranostic nanoplatform for efficient cancer theranostics, but also provides a new strategy for the development of safe and efficient new anti-tumor therapies" }, { "pmid": "34251693", "year": 2021, "title": "Safety of electrooxidation for urea removal in a wearable artificial kidney is compromised by formation of glucose degradation products.", "title_en": null, "title_de": "Die Sicherheit der Elektrooxidation zur Harnstoffentfernung in einer tragbaren künstlichen Niere wird durch die Bildung von Glukose-Abbauprodukten beeinträchtigt", "journal": "Artificial organs", "authors": "van Gelder et al.", "author_search": "van gelder van gelder", "doi": "10.1111/aor.14040", "doi_url": "https://doi.org/10.1111/aor.14040", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/34251693/", "url": "https://h2medicine.org/studies/study-vangelder-2021-electrooxidation-urea-removal-wearable/", "methods": [ "inhalation" ], "indications": [ "kidney-dialysis", "fundamentals-safety" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2021 · van Gelder et al. — Safety of Electrooxidation for Urea Removal in a Wearable Artificial Kidney Is Compromised by Formation of Glucose Degradation Products", "summary": "A wearable artificial kidney (WAK) using electrooxidation to destroy urea in dialysate generates dangerous glucose degradation products — making the current approach unsafe for clinical use. Hydrogen gas is a byproduct of the electrooxidation process, not a therapeutic intervention. This is an in-vitro safety engineering study with no relevance to biomedical hydrogen therapy.", "assessment": "This study is not relevant to biomedical hydrogen therapy. Hydrogen gas is generated as an incidental byproduct of an electrochemical urea conversion process in a dialysis engineering experiment. The paper contributes to the wearable artificial kidney literature by identifying a critical safety barrier for electrooxidation. It should not be cited in any context related to therapeutic molecular hydrogen.", "abstract": "A major challenge for the development of a wearable artificial kidney (WAK) is the removal of urea from the spent dialysate, as urea is the waste solute with the highest daily molar production and is difficult to adsorb. Here we present results on glucose degradation products (GDPs) formed during electrooxidation (EO), a technique that applies a current to the dialysate to convert urea into nitrogen, carbon dioxide, and hydrogen gas. Uremic plasma and peritoneal effluent were dialyzed for 8 hours with a WAK with and without EO-based dialysate regeneration. Samples were taken regularly during treatment. GDPs (glyoxal, methylglyoxal, and 3-deoxyglucosone) were measured in EO- and non-EO-treated fluids. Glyoxal and methylglyoxal concentrations increased 26- and 11-fold, respectively, in uremic plasma (at [glucose] 7 mmol/L) and 209- and 353-fold, respectively, in peritoneal effluent (at [glucose] 100 mmol/L) during treatment with EO, whereas no change was observed in GDP concentrations during dialysate regeneration without EO. EO for dialysate regeneration in a WAK is currently not safe due to the generation of GDPs which are not biocompatible.", "conclusion": "Glyoxal and methylglyoxal concentrations increased 26- and 11-fold, respectively, in uremic plasma (at [glucose] 7 mmol/L) and 209- and 353-fold, respectively, in peritoneal effluent (at [glucose] 100 mmol/L) during treatment with EO, whereas no change was observed in GDP concentrations during dialysate regeneration without EO. EO for dialysate regeneration in a WAK is currently not safe due to th" }, { "pmid": "34120062", "year": 2021, "title": "Microbial food from light, carbon dioxide and hydrogen gas: Kinetic, stoichiometric and nutritional potential of three purple bacteria.", "title_en": null, "title_de": "Mikrobielle Nahrung aus Licht, Kohlendioxid und Wasserstoffgas: Kinetisches, stöchiometrisches und ernährungsphysiologisches Potenzial dreier Purpurbakterien", "journal": "Bioresource technology", "authors": "Spanoghe et al.", "author_search": "spanoghe spanoghe", "doi": "10.1016/j.biortech.2021.125364", "doi_url": "https://doi.org/10.1016/j.biortech.2021.125364", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/34120062/", "url": "https://h2medicine.org/studies/study-spanoghe-2021-microbial-food-light-carbon/", "methods": [ "inhalation" ], "indications": [ "sports-exercise" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2021 · Spanoghe et al. — Microbial Food from Light, Carbon Dioxide and Hydrogen Gas: Kinetic, Stoichiometric and Nutritional Potential of Three Purple Bacteria", "summary": "Purple bacteria can grow using light, CO₂, and hydrogen gas as their sole energy and carbon sources, producing protein-rich biomass with complete dietary amino acid profiles. This is a biotechnology/food science study on sustainable microbial protein production — not a study on hydrogen therapy or the health effects of H₂ in humans or animals.", "assessment": "This is a sound biotechnology study with clear relevance to sustainable protein production. The results are well-characterized and the comparison with competing microbial systems is methodologically appropriate. Relevance to H₂ medicine: none. Molecular hydrogen is a bacterial substrate here, not a health intervention. This study was likely retrieved by keyword search on H2 in the context of its role as a bacterial energy source. It should not be cited as evidence for any health effect of hydrogen on humans or animals.", "abstract": "The urgency for a protein transition towards more sustainable solutions is one of the major societal challenges. Microbial protein is one of the alternative routes, in which land- and fossil-free production should be targeted. The photohydrogenotrophic growth of purple bacteria, which builds on the H2- and CO2-economy, is unexplored for its microbial protein potential. The three tested species (Rhodobacter capsulatus, Rhodobacter sphaeroides and Rhodopseudomonas palustris) obtained promising growth rates (2.3-2.7 d-1 at 28°C) and protein productivities (0.09-0.12 g protein L-1 d-1), rendering them likely faster and more productive than microalgae. The achieved protein yields (2.6-2.9 g protein g-1 H2) transcended the ones of aerobic hydrogen oxidizing bacteria. Furthermore, all species provided full dietary protein matches for humans and their fatty acid content was dominated by vaccenic acid (82-86%). Given its kinetic and nutritional performance we recommend to consider Rhodobacter capsulatus as a high-potential sustainable source of microbial food.", "conclusion": "Furthermore, all species provided full dietary protein matches for humans and their fatty acid content was dominated by vaccenic acid (82-86%). Given its kinetic and nutritional performance we recommend to consider Rhodobacter capsulatus as a high-potential sustainable source of microbial food." }, { "pmid": "34085924", "year": 2021, "title": "Reshaping of bacterial molecular hydrogen metabolism contributes to the outgrowth of commensal E. coli during gut inflammation.", "title_en": null, "title_de": "Die Umgestaltung des bakteriellen Stoffwechsels von molekularem Wasserstoff trägt zum Auswachsen kommensaler E. coli während einer Darmentzündung bei", "journal": "eLife", "authors": "Hughes et al.", "author_search": "hughes hughes", "doi": "10.7554/elife.58609", "doi_url": "https://doi.org/10.7554/elife.58609", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/34085924/", "url": "https://h2medicine.org/studies/study-hughes-2021-reshaping-bacterial-metabolism-contributes/", "methods": [ "unspecified" ], "indications": [ "immune-system" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2021 · Hughes — Reshaping of bacterial molecular hydrogen metabolism contributes to the outgrowth of commensal E. coli during gut inflammation", "summary": "During intestinal inflammation, certain gut bacteria — including E. coli — gain a competitive advantage by ramping up their ability to consume molecular hydrogen (H₂). This in-vitro and mouse-model study shows that bacterial hydrogenases are not just bystanders but active participants in the microbial reshaping that occurs in inflammatory bowel disease. The research does not address therapeutic H₂ supplementation in humans.", "assessment": "An important mechanistic finding for microbiome research: it explains, at least partially, why Enterobacteriaceae bloom during intestinal inflammation. This is, however, a preclinical study (cell culture + mouse colitis model), and its findings relate to the bacterial consumption of endogenous gut H₂ — not to therapeutic administration of exogenous H₂ to humans. The data cannot be used to derive clinical recommendations. The metagenomics reanalysis of human IBD datasets is suggestive but correlative; causality in humans remains unproven.", "abstract": "The composition of gut-associated microbial communities changes during intestinal inflammation, including an expansion of Enterobacteriaceae populations. The mechanisms underlying microbiota changes during inflammation are incompletely understood. Here, we analyzed previously published metagenomic datasets with a focus on microbial hydrogen metabolism. The bacterial genomes in the inflamed murine gut and in patients with inflammatory bowel disease contained more genes encoding predicted hydrogen-utilizing hydrogenases compared to communities found under non-inflamed conditions. To validate these findings, we investigated hydrogen metabolism of Escherichia coli, a representative Enterobacteriaceae, in mouse models of colitis. E. coli mutants lacking hydrogenase-1 and hydrogenase-2 displayed decreased fitness during colonization of the inflamed cecum and colon. Utilization of molecular hydrogen was in part dependent on respiration of inflammation-derived electron acceptors. This work highlights the contribution of hydrogenases to alterations of the gut microbiota in the context of non-infectious colitis.", "conclusion": "Utilization of molecular hydrogen was in part dependent on respiration of inflammation-derived electron acceptors. This work highlights the contribution of hydrogenases to alterations of the gut microbiota in the context of non-infectious colitis." }, { "pmid": "34080660", "year": 2021, "title": "Mechanism of hydrogen on cervical cancer suppression revealed by high‑throughput RNA sequencing.", "title_en": null, "title_de": "Mechanismus der Wasserstoff-vermittelten Unterdrückung von Gebärmutterhalskrebs, aufgedeckt durch Hochdurchsatz-RNA-Sequenzierung", "journal": "Oncology reports", "authors": "Chu et al.", "author_search": "chu chu", "doi": "10.3892/or.2021.8092", "doi_url": "https://doi.org/10.3892/or.2021.8092", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/34080660/", "url": "https://h2medicine.org/studies/study-chu-2021-mechanism-cervical-cancer-suppression/", "methods": [ "inhalation" ], "indications": [ "cancer", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2021 · Chu — Mechanism of hydrogen on cervical cancer suppression revealed by high-throughput RNA sequencing", "summary": "H₂ inhalation suppressed the growth of cervical cancer cells in the laboratory and in a mouse xenograft model, apparently by switching off two key cancer-promoting proteins — HIF-1α and NF-κB p65. RNA sequencing helped map the molecular pathway. These are cell-culture and animal findings; no human patients were involved.", "assessment": "This is a preclinical study — HeLa cell culture plus a mouse xenograft model. The data are biologically interesting and the methodology is solid for its scope, but results cannot be extrapolated to human cancer therapy. HeLa cells are a highly artificial system (immortalised, heavily mutated), and xenograft models in immunocompromised mice routinely overestimate anti-tumour effects. Clinical trials in humans would be required to draw any therapeutic conclusions. The authors' own language — „may serve as a potential therapeutic target“ — correctly signals the preliminary nature of these findings.", "abstract": "Cervical cancer is considered one of the diseases with the highest mortality among women and with limited treatment options. Hydrogen (H2) inhalation has been reported to have a variety of tumor‑suppressive effects, but the exact mechanism remains unclear. In the present study, HeLa cervical cancer cells and HaCaT keratinocytes treated with H2, and a HeLa xenograft mouse model subjected to H2 inhalation were established. TUNEL, Cell Counting Kit‑8 and Ki67 staining assays were used to detect cell apoptosis and proliferation. Oxidative stress was determined according to the levels of reactive oxygen species, malondialdehyde and superoxide dismutase. Tumor growth was recorded every 3 days, and the excised tumors were stained with hematoxylin and eosin. High‑throughput RNA sequencing and subsequent Gene Ontology (GO) enrichment analysis were performed in HeLa‑treated and un‑treated HeLa cells. The expression of hypoxia‑inducible factor (HIF)‑1α and NF‑κB p65 was verified by western blotting, immunohistochemistry and reverse transcription‑quantitative PCR. The results revealed an increased apoptosis rate, and reduced cell proliferation and oxidative stress in H2‑treated HeLa cells but not in HaCaT cells. Similarly, decreased tumor growth and cell proliferation, and enhanced cell apoptosis were observed in H2‑treated HeLa tumors. RNA sequencing and GO analysis suggest that downregulated HIF1A (HIF‑1α mRNA) and RelA (NF‑κB p65) levels, and reduced NF‑κB signaling were associated with the antitumor effect of H2. Finally, decreased HIF‑1α and NF‑κB p65 expression both at the transcriptional and translational levels were observed in H2‑treated HeLa cells and in HeLa‑derived tumors. In conclusion, the present study reveals a novel mechanism of H2 against cervical cancer, which may serve as a potential therapeutic target in clinical practice.", "conclusion": "Finally, decreased HIF‑1α and NF‑κB p65 expression both at the transcriptional and translational levels were observed in H2‑treated HeLa cells and in HeLa‑derived tumors. In conclusion, the present study reveals a novel mechanism of H2 against cervical cancer, which may serve as a potential therapeutic target in clinical practice." }, { "pmid": "33899541", "year": 2021, "title": "Effects of hydrogen as adjuvant treatment for unstable angina.", "title_en": null, "title_de": "Wirkungen von Wasserstoff als adjuvante Behandlung bei instabiler Angina pectoris", "journal": "Experimental biology and medicine (Maywood, N.J.)", "authors": "Si et al.", "author_search": "si si", "doi": "10.1177/15353702211009138", "doi_url": "https://doi.org/10.1177/15353702211009138", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33899541/", "url": "https://h2medicine.org/studies/study-si-2021-adjuvant-unstable-angina/", "methods": [ "drinking-hrw" ], "indications": [ "metabolic", "cardiovascular", "immune-system", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2021 · Si — Effects of hydrogen as adjuvant treatment for unstable angina", "summary": "In 40 patients with unstable angina, adding hydrogen-rich water to standard drug therapy for three months reduced angina symptoms and produced greater reductions in total cholesterol, LDL-cholesterol, and apolipoprotein B compared to standard treatment alone. In-vitro work showed H₂ also suppresses the inflammatory pathway driving atherosclerosis. (Experimental Biology and Medicine, 2021.)", "assessment": "A well-structured combined mechanistic and clinical study, though modest in size. The in-vitro/in-vivo pairing strengthens mechanistic plausibility. The clinical findings are consistent with H₂'s known antioxidant and anti-inflammatory properties. Limitations: n=40 (20/20 allocation implied) is underpowered for hard cardiovascular endpoints; the study period is 3 months — too short to observe event-level outcomes; blinding quality of the HRW vs. placebo water is not explicitly described; the journal is of moderate impact. Angina symptom rating is subjective. The lipid reductions are the most objective and convincing finding.", "abstract": "Oxidative stress and inflammation are closely related to atherosclerotic cardiovascular disease. It is established that hydrogen has significant protective effects on many diseases as a potential antioxidative and anti-inflammatory agent. The purpose of this study is to evaluate the effect of hydrogen on unstable angina in vitro and in vivo. An atherosclerosis model in vitro was constructed by ox-LDL-induced injury of human umbilical vein endothelial cells and in vitro testing indicated hydrogen inhibited ox-LDL-induced oxidative stress and inflammatory response by down-regulating LOX-1/NF-kB signaling pathway. Subsequently, the attenuating effect of hydrogen-rich water intake on unstable angina was further confirmed in clinic. Forty hospitalized subjects with unstable angina were enrolled and consumed either 1000-1200 mL/d hydrogen-rich water or the same amount of placebo pure water in addition to conventional drugs for three months. Clinical analysis showed hydrogen-rich water intake relieved angina symptoms in unstable angina patients. Serum analysis showed that hydrogen-rich water addition resulted in more effective reductions of total-cholesterol, low-density lipoprotein-cholesterol, and apolipoprotein B levels compared with conventional treatment. These results support that hydrogen as adjuvant treatment has a beneficial effect on unstable angina.", "conclusion": "Serum analysis showed that hydrogen-rich water addition resulted in more effective reductions of total-cholesterol, low-density lipoprotein-cholesterol, and apolipoprotein B levels compared with conventional treatment. These results support that hydrogen as adjuvant treatment has a beneficial effect on unstable angina." }, { "pmid": "33852061", "year": 2021, "title": "Molecular hydrogen alleviates asthma through inhibiting IL-33/ILC2 axis.", "title_en": null, "title_de": "Molekularer Wasserstoff lindert Asthma durch Hemmung der IL-33/ILC2-Achse", "journal": "Inflammation research : official journal of the European Histamine Research Society ... [et al.]", "authors": "Zhang et al.", "author_search": "zhang zhang", "doi": "10.1007/s00011-021-01459-w", "doi_url": "https://doi.org/10.1007/s00011-021-01459-w", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33852061/", "url": "https://h2medicine.org/studies/study-zhang-2021-alleviates-asthma-through-inhibiting/", "methods": [ "inhalation" ], "indications": [ "respiratory", "immune-system", "allergy" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2021 · Zhang — Molecular hydrogen alleviates asthma through inhibiting IL-33/ILC2 axis", "summary": "In an OVA-sensitised mouse model of asthma and a bronchial epithelial cell model, hydrogen/oxygen gas mixture inhalation markedly reduced allergic inflammation by suppressing the IL-33/ILC2 signalling axis. The study combines in-vivo and in-vitro methods and proposes a miRNA-linked mechanism. All findings are preclinical — no human asthma patients were studied.", "assessment": "A well-designed preclinical study (mouse + bronchial cell line) that identifies a plausible molecular target (IL-33/ILC2) for H₂'s anti-asthmatic effects. The miRNA data add an additional mechanistic layer. Critical limitations: OVA sensitisation is a standard but highly artificial asthma model that does not fully recapitulate human atopic asthma; ILC2 biology in mice and humans differs in important ways. No clinical conclusions can be drawn. The study is a useful hypothesis generator for future human trials.", "abstract": "BACKGROUND: Asthma is one of the most common noninfectious chronic diseases characterized by type II inflammation. This study aimed to investigate the effects of molecular hydrogen on the pathogenesis of asthma. METHODS: OVA sensitized asthma mouse model and house dust mite treated 16HBE cellular model were established and hydrogen/oxygen mixture was used to treat asthmatic mice and 16HBE cells. Serum and BALF cytokines were measured with specific ELISA assays. E-cadherin and ZO-1 were detected by immunohistochemical staining and expression of caspase 3 and 9, NF-κB, IL-33 and ST2 was assessed by quantitative real-time PCR, western blot and/or immunofluorescence. IL-33 promoter activity was analyzed by dual-luciferase assay. ILC2 population was assayed by flow cytometry and differentially expressed miRNAs were detected using miRNA array. RESULTS: Serum and BALF levels of IL-33 and other alarmin and type II cytokines were greatly increased by OVA and inhibited by H2 in asthmatic mice. The expression of NF-κB (p65) and ST2 was upregulated by OVA and suppressed by H2. ILC2 population was markedly increased in OVA-induced asthmatic mice, and such increase was inhibited by H2. E-cadherin and ZO-1 levels in airway tissues of asthmatic mice were significantly lower than that of control mice, and the reduction was recovered by H2 treatment. H2 alleviated HDM induced apoptosis of 16HBE cells, upregulation of IL-33 and ST2, and elevation of IL-33 promoter activity. A group of miRNAs differentially expressed in HDM and HDM + H2 treated 16HBE cells were identified. CONCLUSIONS: These data demonstrated that H2 is efficient in suppressing allergen-induced asthma and could be developed as a therapeutics for asthma and other conditions of type II inflammation.", "conclusion": "These data demonstrated that H2 is efficient in suppressing allergen-induced asthma and could be developed as a therapeutics for asthma and other conditions of type II inflammation." }, { "pmid": "33783052", "year": 2021, "title": "Investigations of Dianhydro-D-glucitol adsorbed on AuNPs surface: In silico and in vitro approach based on anticancer activity studies against A549 lung cancer cell lines.", "title_en": null, "title_de": "Untersuchungen zu Dianhydro-D-glucitol, adsorbiert an der Oberfläche von AuNPs: In-silico- und In-vitro-Ansatz auf Basis von Antikrebsaktivitätsstudien gegen A549-Lungenkrebszelllinien", "journal": "Journal of molecular recognition : JMR", "authors": "V et al.", "author_search": "v v", "doi": "10.1002/jmr.2899", "doi_url": "https://doi.org/10.1002/jmr.2899", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33783052/", "url": "https://h2medicine.org/studies/study-v-2021-investigations-dianhydro-glucitol-adsorbed/", "methods": [ "unspecified" ], "indications": [ "liver", "cancer", "respiratory" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2021 · V — Investigations of Dianhydro-D-glucitol adsorbed on AuNPs surface: In silico and in vitro approach based on anticancer activity studies against A549 lung cancer cell lines", "summary": "This in-vitro and computational chemistry study examined how attaching a lung-cancer drug (Dianhydro-D-glucitol) to gold nanoparticles affects its anticancer behaviour against A549 lung cancer cells. Molecular hydrogen enters the picture only as a structural feature (intramolecular hydrogen bonds) studied via density-functional theory — this is not a study of molecular H₂ as a biological or therapeutic agent.", "assessment": "This study is not about molecular hydrogen (H₂) as a therapeutic agent. It is a computational + in-vitro chemistry paper on gold-nanoparticle drug delivery for a specific chemotherapy compound. The word „hydrogen“ appears only in the context of intramolecular hydrogen bonds — a standard chemical feature of any organic molecule. No evidence is provided for or against H₂ therapy. The study's relevance to hydrogen medicine is zero; its inclusion appears to be a database indexing artefact.", "abstract": "The adsorption behavior of a lung cancer agent, Dianhydro-D-glucitol (DIS) on gold nanoparticles (AuNPs) was studied using surface-enhanced Raman scattering techniques. The stabilized geometry, inter- and intra-molecular hydrogen bond, and harmonic vibrational wavenumbers of DIS and DIS adsorbed on AuNPs (DISA) surface have been investigated with the help of the density functional theory (DFT) method. The stability of the molecules arising from stereoelectronic interactions, leading to its bioactivity, has been confirmed using natural bond orbital (NBO) analysis, which was further substantiated by the narrow HOMO LUMO energy gap obtained for DISA, from frontier molecular orbital analysis as well as electronic spectral analysis. The molecular electrostatic potential analysis along with local and global reactivity descriptors predicts the reactive site of the molecules. Molecular docking study was performed to obtain information about protein-ligand reactions for DIS and DISA, with different cancer proteins. This study enlightens the potential of SERS agents for targeted drug delivery and photothermal. The in vitro cytotoxic effects of DPH and DPHA molecules on lung cancer cell lines were analyzed using the MTT assay and the SERS method.", "conclusion": "This study enlightens the potential of SERS agents for targeted drug delivery and photothermal. The in vitro cytotoxic effects of DPH and DPHA molecules on lung cancer cell lines were analyzed using the MTT assay and the SERS method." }, { "pmid": "33767697", "year": 2021, "title": "Hydrogen Attenuates Endotoxin-Induced Lung Injury by Activating Thioredoxin 1 and Decreasing Tissue Factor Expression.", "title_en": null, "title_de": "Wasserstoff mindert endotoxininduzierte Lungenschäden durch Aktivierung von Thioredoxin 1 und Senkung der Expression von Gewebefaktor", "journal": "Frontiers in immunology", "authors": "Li et al.", "author_search": "li li", "doi": "10.3389/fimmu.2021.625957", "doi_url": "https://doi.org/10.3389/fimmu.2021.625957", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33767697/", "url": "https://h2medicine.org/studies/study-li-2021-attenuates-endotoxin-induced-lung/", "methods": [ "inhalation" ], "indications": [ "respiratory", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2021 · Li — Hydrogen Attenuates Endotoxin-Induced Lung Injury by Activating Thioredoxin 1 and Decreasing Tissue Factor Expression", "summary": "In a mouse model of endotoxin-induced lung injury, H₂ inhalation significantly improved survival, reduced pulmonary oedema, and decreased neutrophil infiltration — apparently by activating the antioxidant protein Thioredoxin 1 (Trx1), which in turn suppressed tissue factor (TF) and MMP-9. This preclinical study identifies Trx1 as a likely mechanistic mediator. No human patients were involved.", "assessment": "A mechanistically focused preclinical study that goes beyond demonstrating an effect to identifying a specific molecular target (Trx1). The use of a pharmacological inhibitor (PX12) to confirm the causal role of Trx1 is a methodological strength. Limitations: all evidence is from LPS-challenged mice and cultured cell lines (THP-1, HUVEC-C) — standard but simplified models of septic lung injury. Whether Trx1 activation by H₂ plays the same role in human endotoxemia or ALI is unknown. No clinical translation can be assumed at this stage.", "abstract": "Endotoxin-induced lung injury is one of the major causes of death induced by endotoxemia, however, few effective therapeutic options exist. Hydrogen inhalation has recently been shown to be an effective treatment for inflammatory lung injury, but the underlying mechanism is unknown. In the current study we aim to investigate how hydrogen attenuates endotoxin-induced lung injury and provide reference values for the clinical application of hydrogen. LPS was used to establish an endotoxin-induced lung injury mouse model. The survival rate and pulmonary pathologic changes were evaluated. THP-1 and HUVECC cells were cultured in vitro. The thioredoxin 1 (Trx1) inhibitor was used to evaluate the anti-inflammatory effects of hydrogen. Hydrogen significantly improved the survival rate of mice, reduced pulmonary edema and hemorrhage, infiltration of neutrophils, and IL-6 secretion. Inhalation of hydrogen decreased tissue factor (TF) expression and MMP-9 activity, while Trx1 expression was increased in the lungs and serum of endotoxemia mice. LPS-stimulated THP-1 and HUVEC-C cells in vitro and showed that hydrogen decreases TF expression and MMP-9 activity, which were abolished by the Trx1 inhibitor, PX12. Hydrogen attenuates endotoxin-induced lung injury by decreasing TF expression and MMP-9 activity via activating Trx1. Targeting Trx1 by hydrogen may be a potential treatment for endotoxin-induced lung injury.", "conclusion": "Hydrogen attenuates endotoxin-induced lung injury by decreasing TF expression and MMP-9 activity via activating Trx1. Targeting Trx1 by hydrogen may be a potential treatment for endotoxin-induced lung injury." }, { "pmid": "33642332", "year": 2021, "title": "High-flow hydrogen inhalation might suppresses the immune function of middle-aged participants: a self-controlled study.", "title_en": null, "title_de": "Hochfluss-Wasserstoffinhalation könnte die Immunfunktion von Teilnehmern mittleren Alters unterdrücken: eine eigenkontrollierte Studie", "journal": "Medical gas research", "authors": "Chen et al.", "author_search": "chen chen", "doi": "10.4103/2045-9912.310054", "doi_url": "https://doi.org/10.4103/2045-9912.310054", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33642332/", "url": "https://h2medicine.org/studies/study-chen-2021-high-flow-inhalation-might/", "methods": [ "inhalation" ], "indications": [ "cancer", "immune-system" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2021 · Chen — High-flow hydrogen inhalation might suppress the immune function of middle-aged participants: a self-controlled study", "summary": "Twenty healthy adults who inhaled hydrogen at high flow rates for 2–4 hours daily over two weeks showed significant decreases in several immune cell populations, including T helper cells, NK cells, and gamma delta T cells. This finding raises an important caution: while standard-dose H₂ inhalation is generally considered safe, high-flow delivery may temporarily suppress immune function. (Medical Gas Research, 2021.)", "assessment": "A critical safety-signal study that the H₂ field should take seriously. It adds an important caveat to the common assumption that H₂ inhalation is universally safe at any flow rate. Limitations: n=20, self-controlled design (no concurrent control group), no washout period described, reversibility of immune changes not assessed, clinical outcomes not measured, population is middle-aged healthy adults (results may not generalise). The immune changes may be transient — but we do not know. This finding warrants follow-up studies specifically designed to test dose-response, reversibility, and clinical significance of high-flow H₂ on immunity.", "abstract": "Hydrogen inhalation therapy has been proven to be safe and effective in disease treatment in multiple clinical reports, but the gas flow rates used in different studies vary greatly. Since there is no upper limit for the safe concentration of hydrogen, this study tested the effects of high-flow (not high concentration) hydrogen inhalation on immune function. From October 2019 to January 2020, 20 adult participants (31-60 years old) were enrolled in a self-controlled study to check the immune function in peripheral blood lymphocyte subsets before and after a 2-week hydrogen inhalation protocol. The participants inhaled hydrogen for 2 or 4 hours each day. After 2 weeks of hydrogen inhalation, statistically significant changes were observed in follicular helper T cells, helper and cytotoxic T cells, natural killer and natural killer T cells, and gamma delta T cells, generally suggesting a decrease in their proportions. These results show that high-flow hydrogen inhalation has an inhibitory effect on the immune function of healthy participants. The study protocol received ethical approval from the Ethics Committee of Fuda Cancer Hospital, Jinan University on December 7, 2018 (approval No. Fuda20181207).", "conclusion": "The study protocol received ethical approval from the Ethics Committee of Fuda Cancer Hospital, Jinan University on December 7, 2018 (approval No. Fuda20181207)." }, { "pmid": "33639371", "year": 2021, "title": "Hydrogen Gas Therapy Attenuates Inflammatory Pathway Signaling in Septic Mice.", "title_en": null, "title_de": "Wasserstoffgas-Therapie schwächt die Signalübertragung des Entzündungswegs bei septischen Mäusen ab", "journal": "The Journal of surgical research", "authors": "Matsuura et al.", "author_search": "matsuura matsuura", "doi": "10.1016/j.jss.2021.01.022", "doi_url": "https://doi.org/10.1016/j.jss.2021.01.022", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33639371/", "url": "https://h2medicine.org/studies/study-matsuura-2021-attenuates-inflammatory-pathway-signaling/", "methods": [ "inhalation" ], "indications": [ "liver", "cancer", "respiratory", "immune-system" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2021 · Matsuura — Hydrogen Gas Therapy Attenuates Inflammatory Pathway Signaling in Septic Mice", "summary": "In a mouse cecal ligation and puncture (CLP) sepsis model, continuous H₂ inhalation improved 7-day survival from 40% to 75% and suppressed systemic and organ-level inflammatory signalling. RNA sequencing of liver, intestine, and lungs revealed that H₂ inactivated multiple canonical inflammatory pathways. This is a preclinical study in mice — no human sepsis patients were studied.", "assessment": "A technically solid preclinical study in an established sepsis model, with the added value of multi-organ transcriptomics. The survival data are encouraging but must be interpreted cautiously: CLP survival outcomes in mice rarely translate directly to human sepsis clinical trials. The RNA-seq findings are exploratory and require independent validation. The authors appropriately frame their conclusion as contributing to „clarifying the mechanism of action“ rather than claiming clinical proof. No therapeutic recommendation for humans can be derived from this data.", "abstract": "BACKGROUND: Molecular hydrogen (H2) has been used in clinical cases. However, there are few studies of H2 therapy to treat sepsis, and anti-inflammatory mechanisms of H2 are mostly unknown. We aimed to confirm effects of H2 therapy on sepsis and reveal its therapeutic mechanism via RNA sequencing in multiple organs in septic mice. METHODS: Nine-week-old C57BL/6 male mice underwent cecal ligation and puncture (CLP) or sham procedure. Subsequently, the CLP model received immediate ± continuous inhalation of 7% H2. Mice were observed for a week to assess survival rates. Serum inflammatory cytokines were evaluated at 24 h after CLP procedure. Liver, intestine, and lungs in CLP mice receiving 24-h ± H2 therapy were assessed by RNA sequencing. Data were analyzed with Ingenuity Pathways Analysis (QIAGEN Inc). RESULTS: Seven-day survival rate in septic mice was significantly improved in the H2 inhalation group compared with that in the control group (75% versus 40%, P < 0.05). H2 treatment attenuated serum interleukin-6 and tumor necrosis factor-α levels at 24 h after CLP, and blood glucose levels were maintained in the H2-treated group. In RNA sequencing, canonical pathway analysis revealed inactivity of various inflammatory signaling pathways, for example, acute phase response signaling and STAT3 pathways, in the liver and intestine in the CLP model after 24-h H2 inhalation. We detected significantly decreased expressions of upstream regulator genes such as the CD14 antigen gene in the liver and various cytokine receptor genes in the intestine and lungs in the H2-treated group. CONCLUSIONS: These findings may contribute to clarifying the mechanism of action of H2 therapy in sepsis.", "conclusion": "These findings may contribute to clarifying the mechanism of action of H2 therapy in sepsis." }, { "pmid": "33485760", "year": 2021, "title": "Hydrogen as a Potential Therapeutic in Obesity: Targeting the Brain.", "title_en": null, "title_de": "Wasserstoff als potenzielles Therapeutikum bei Adipositas: Das Gehirn als Zielstruktur", "journal": "Trends in endocrinology and metabolism: TEM", "authors": "Ostojic", "author_search": "ostojic ostojic", "doi": "10.1016/j.tem.2021.01.002", "doi_url": "https://doi.org/10.1016/j.tem.2021.01.002", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33485760/", "url": "https://h2medicine.org/studies/study-ostojic-2021-therapeutic-obesity-targeting-brain/", "methods": [ "inhalation" ], "indications": [ "metabolic", "neurology" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Ostojic — Hydrogen as a Potential Therapeutic in Obesity: Targeting the Brain", "summary": "This short review considers whether molecular H₂ could act directly on brain structures involved in obesity regulation — particularly the hypothalamus. The author notes that H₂ appears to improve obesity-related metabolic markers in peripheral tissues in clinical settings, but whether it reaches and acts on central neural pathways remains speculative. This is a theoretical review, not a clinical trial.", "assessment": "This is a short theoretical review by a single author, presenting a hypothesis that H₂ might act on brain obesity pathways. It does not present new experimental data; the mechanistic claims are extrapolations from peripheral tissue studies and from known H₂ biology (antioxidative, anti-inflammatory). The central question the review poses — whether H₂ crosses the blood-brain barrier in sufficient quantity to alter hypothalamic signalling — remains open. This is hypothesis-generating for future research, not a basis for clinical application. Readers should note the absence of clinical or animal brain-specific H₂ data in support of the proposed mechanisms.", "abstract": "Clinical applications of molecular hydrogen (H2) seem to favorably affect obesity-related metabolic biomarkers in peripheral tissues, yet whether H2 directly tackles obesity pathways in the brain remains elusive. I summarize here several molecular targets in the hypothalamus and beyond that could be altered by H2 gas in obesity.", "conclusion": "Clinical applications of molecular hydrogen (H2) seem to favorably affect obesity-related metabolic biomarkers in peripheral tissues, yet whether H2 directly tackles obesity pathways in the brain remains elusive. I summarize here several molecular targets in the hypothalamus and beyond that could be altered by H2 gas in obesity." }, { "pmid": "33478090", "year": 2021, "title": "Toward Tailoring the Degradation Rate of Magnesium-Based Biomaterials for Various Medical Applications: Assessing Corrosion, Cytocompatibility and Immunological Effects.", "title_en": null, "title_de": "Auf dem Weg zur Anpassung der Abbaurate magnesiumbasierter Biomaterialien für verschiedene medizinische Anwendungen: Bewertung von Korrosion, Zytokompatibilität und immunologischen Effekten", "journal": "International journal of molecular sciences", "authors": "Hartjen et al.", "author_search": "hartjen hartjen", "doi": "10.3390/ijms22020971", "doi_url": "https://doi.org/10.3390/ijms22020971", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33478090/", "url": "https://h2medicine.org/studies/study-hartjen-2021-toward-tailoring-degradation-rate/", "methods": [ "inhalation", "bath-topical" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2021 · Hartjen — Toward Tailoring the Degradation Rate of Magnesium-Based Biomaterials for Various Medical Applications: Assessing Corrosion, Cytocompatibility and Immunological Effects", "summary": "This in-vitro materials science study tested a surface-treated magnesium alloy (WE43 with plasma electrolytic oxidation) as a degradable implant material. Molecular hydrogen appears here as a corrosion by-product generated when magnesium degrades in body fluids — not as a therapeutic agent. The surface treatment reduced H₂ gas evolution by ~41% and dramatically improved cell compatibility.", "assessment": "This study is not about molecular H₂ therapy. It is a biomaterials science paper evaluating a magnesium alloy coating for degradable implants. Hydrogen gas is measured as an unwanted corrosion by-product — its reduction is the goal, not its promotion. No evidence is presented for or against therapeutic H₂ use in humans. The study's relevance to H₂ medicine is indirect at most: it documents that corroding magnesium implants generate H₂, which may eventually inform discussions about local H₂ exposure in implant-bearing tissue — but this is speculative and not discussed in the paper.", "abstract": "Magnesium (Mg)-based biomaterials hold considerable promise for applications in regenerative medicine. However, the degradation of Mg needs to be reduced to control toxicity caused by its rapid natural corrosion. In the process of developing new Mg alloys with various surface modifications, an efficient assessment of the relevant properties is essential. In the present study, a WE43 Mg alloy with a plasma electrolytic oxidation (PEO)-generated surface was investigated. Surface microstructure, hydrogen gas evolution in immersion tests and cytocompatibility were assessed. In addition, a novel in vitro immunological test using primary human lymphocytes was introduced. On PEO-treated WE43, a larger number of pores and microcracks, as well as increased roughness, were observed compared to untreated WE43. Hydrogen gas evolution after two weeks was reduced by 40.7% through PEO treatment, indicating a significantly reduced corrosion rate. In contrast to untreated WE43, PEO-treated WE43 exhibited excellent cytocompatibility. After incubation for three days, untreated WE43 killed over 90% of lymphocytes while more than 80% of the cells were still vital after incubation with the PEO-treated WE43. PEO-treated WE43 slightly stimulated the activation, proliferation and toxin (perforin and granzyme B) expression of CD8+ T cells. This study demonstrates that the combined assessment of corrosion, cytocompatibility and immunological effects on primary human lymphocytes provide a comprehensive and effective procedure for characterizing Mg variants with tailorable degradation and other features. PEO-treated WE43 is a promising candidate for further development as a degradable biomaterial.", "conclusion": "This study demonstrates that the combined assessment of corrosion, cytocompatibility and immunological effects on primary human lymphocytes provide a comprehensive and effective procedure for characterizing Mg variants with tailorable degradation and other features. PEO-treated WE43 is a promising candidate for further development as a degradable biomaterial." }, { "pmid": "33475845", "year": 2021, "title": "The prevalence of intestinal dysbiosis in patients referred for antireflux surgery.", "title_en": null, "title_de": "Die Prävalenz der intestinalen Dysbiose bei Patienten, die zur Antireflux-Chirurgie überwiesen wurden", "journal": "Surgical endoscopy", "authors": "Haworth et al.", "author_search": "haworth haworth", "doi": "10.1007/s00464-020-08229-5", "doi_url": "https://doi.org/10.1007/s00464-020-08229-5", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33475845/", "url": "https://h2medicine.org/studies/study-haworth-2021-prevalence-intestinal-dysbiosis-referred/", "methods": [], "indications": [ "other" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "breath-test", "headline": "2021 · Haworth — The prevalence of intestinal dysbiosis in patients referred for antireflux surgery", "summary": "In 104 patients evaluated for antireflux surgery, 60.6% had intestinal dysbiosis — with small intestinal bacterial overgrowth (SIBO) detected by hydrogen breath testing in 39.4% of cases. Hydrogen here is a diagnostic marker produced by gut bacteria, not a therapeutic agent; but the study highlights that gut-produced H₂ may contribute to reflux symptoms misattributed to acid alone. (Surgical Endoscopy, 2021.)", "assessment": "A clinically relevant gastroenterological study using hydrogen breath testing as a diagnostic tool. Its contribution to the H₂ field is in the diagnostic/physiological domain — not therapeutic H₂ supplementation. Limitations: retrospective design, single centre, no follow-up post-surgery to show whether treating dysbiosis improved outcomes, breath test thresholds for SIBO vary across laboratories, and the causal direction (does SIBO cause reflux symptoms, or does reflux cause dysbiosis?) is not established. For readers of this database: this study does not assess H₂ as a health supplement — it uses the body's own H₂ production as a window into gut health.", "abstract": "BACKGROUND: Prior to antireflux surgery, most patients with symptoms of gastroesophageal reflux disease (GERD) have been taking long-term proton pump inhibitors (PPIs). PPIs have been shown to cause changes to the intestinal microbiota, such as small intestinal bacterial overgrowth (SIBO), which is characterised by symptoms of gas bloating. Patients undergoing antireflux surgery are not routinely screened for SIBO, yet many patients experience gas-related symptoms postoperatively. METHODS: Data from consecutive patients (n = 104) referred to a speciality reflux centre were retrospectively assessed. Patients underwent a routine diagnostic workup for GERD including history, endoscopy, oesophageal manometry and 24-h pH-impedance monitoring off PPIs. Intestinal dysbiosis was determined by hydrogen and methane breath testing with a hydrogen-positive result indicative of SIBO and a methane-positive result indicative of intestinal methanogen overgrowth (IMO). RESULTS: 60.6% of patients had intestinal dysbiosis (39.4% had SIBO and 35.6% had IMO). Patients with dysbiosis were more likely to report bloating (74.6% vs 48.8%; P = 0.01) and belching (60.3% vs 34.1%; P = 0.01). The oesophageal acid exposure time and number of reflux episodes were similar between dysbiosis and non-dysbiosis groups, but patients with dysbiosis were more likely to have a positive reflux-symptom association (76.2% vs 31.7%; P < 0.001), especially for regurgitation in those with SIBO (P = 0.01). Hydrogen gas production was significantly greater in patients with a positive reflux-symptom association for regurgitation (228.8 ppm vs 129.1 ppm, P = 0.004) and belching (mean AUC 214.8 ppm vs 135.9 ppm, P = 0.02). CONCLUSIONS: The prevalence of intestinal dysbiosis is high in patients with GERD, and these patients are more likely to report gas-related symptoms prior to antireflux surgery. Independently, SIBO may be a contributory factor to refractory reflux symptoms and gas bloating in antireflux surgery candidates.", "conclusion": "The prevalence of intestinal dysbiosis is high in patients with GERD, and these patients are more likely to report gas-related symptoms prior to antireflux surgery. Independently, SIBO may be a contributory factor to refractory reflux symptoms and gas bloating in antireflux surgery candidates." }, { "pmid": "33428716", "year": 2021, "title": "Dechloromonas and close relatives prevail during hydrogenotrophic denitrification in stimulated microcosms with oxic aquifer material.", "title_en": null, "title_de": "Dechloromonas und nahe Verwandte dominieren während der hydrogenotrophen Denitrifikation in stimulierten Mikrokosmen mit oxischem Aquifermaterial", "journal": "FEMS microbiology ecology", "authors": "Duffner et al.", "author_search": "duffner duffner", "doi": "10.1093/femsec/fiab004", "doi_url": "https://doi.org/10.1093/femsec/fiab004", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33428716/", "url": "https://h2medicine.org/studies/study-duffner-2021-dechloromonas-close-relatives-prevail/", "methods": [ "inhalation" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2021 · Duffner — Dechloromonas and close relatives prevail during hydrogenotrophic denitrification in stimulated microcosms with oxic aquifer material", "summary": "When hydrogen gas was added to groundwater microcosms contaminated with nitrate, a specific genus of bacteria (Dechloromonas) dominated the resulting nitrate-removal community. This microbiology study examines H₂ as a fuel for environmental bioremediation of nitrate-polluted aquifers — it is entirely unrelated to therapeutic or biological H₂ use in medicine.", "assessment": "This study is environmental microbiology — it uses H₂ gas as an electron donor for bacterial nitrate removal from polluted groundwater. It has no relevance to molecular H₂ as a health or therapeutic agent. Its inclusion in a medical H₂ database appears to be an indexing artefact based on the term „hydrogen.“ The research is methodologically sound within its domain (16S rRNA amplicon sequencing, qPCR of denitrification genes) and addresses a genuine environmental engineering challenge.", "abstract": "Globally occurring nitrate pollution in groundwater is harming the environment and human health. In situ hydrogen addition to stimulate denitrification has been proposed as a remediation strategy. However, observed nitrite accumulation and incomplete denitrification are severe drawbacks that possibly stem from the specific microbial community composition. We set up a microcosm experiment comprising sediment and groundwater from a nitrate polluted oxic oligotrophic aquifer. After the microcosms were sparged with hydrogen gas, samples were taken regularly within 122 h for nitrate and nitrite measurements, community composition analysis via 16S rRNA gene amplicon sequencing and gene and transcript quantification via qPCR of reductase genes essential for complete denitrification. The highest nitrate reduction rates and greatest increase in bacterial abundance coincided with a 15.3-fold increase in relative abundance of Rhodocyclaceae, specifically six ASVs that are closely related to the genus Dechloromonas. The denitrification reductase genes napA, nirS and clade I nosZ also increased significantly over the observation period. We conclude that taxa of the genus Dechloromonas are the prevailing hydrogenotrophic denitrifiers in this nitrate polluted aquifer and the ability of hydrogenotrophic denitrification under the given conditions is species-specific.", "conclusion": "The denitrification reductase genes napA, nirS and clade I nosZ also increased significantly over the observation period. We conclude that taxa of the genus Dechloromonas are the prevailing hydrogenotrophic denitrifiers in this nitrate polluted aquifer and the ability of hydrogenotrophic denitrification under the given conditions is species-specific." }, { "pmid": "33387361", "year": 2021, "title": "Carcinostatic effects of alkanoyl ascorbate plus platinum nano-colloid and stabilization of the esterolytically resultant ascorbate by hydrogen.", "title_en": null, "title_de": "Karzinostatische Wirkungen von Alkanoylascorbat plus Platin-Nanokolloid und Stabilisierung des esterolytisch entstandenen Ascorbats durch Wasserstoff", "journal": "Human cell", "authors": "Kato et al.", "author_search": "kato kato", "doi": "10.1007/s13577-020-00462-3", "doi_url": "https://doi.org/10.1007/s13577-020-00462-3", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33387361/", "url": "https://h2medicine.org/studies/study-kato-2021-carcinostatic-alkanoyl-ascorbate-plus/", "methods": [ "drinking-hrw" ], "indications": [ "cancer", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2021 · Kato — Carcinostatic effects of alkanoyl ascorbate plus platinum nano-colloid and stabilization of the esterolytically resultant ascorbate by hydrogen", "summary": "This in-vitro chemistry study found that a combination of a fatty-acid ascorbate ester (Asc6Palm) plus platinum nanoparticles suppressed human oesophageal cancer cell viability. Hydrogen-rich water appears as a supporting agent that stabilises ascorbate against oxidative breakdown — not as an anticancer therapy on its own. All findings are in cell culture; no human patients were involved.", "assessment": "A specialised in-vitro chemistry study with a narrow scope: the anticancer synergy of a specific ascorbate ester + platinum nanoparticle combination, with HRW playing an antioxidant stabilising role. The work is technically interesting but highly preliminary. The role of H₂ itself as an anticancer agent is not demonstrated here — H₂ is used instrumentally to stabilise ascorbate. The system tested (Asc6Palm + PVP-Pt + HRW) is far from any clinical application. No conclusions about H₂ therapy for cancer or ascorbate therapy in humans can be drawn.", "abstract": "Carcinostatic effects of combined use of ascorbic acid (Asc), 2-O-phospho- or 6-O-palmitoyl ascorbate (Asc2Phos, Asc6Palm) or diverse alkanoyl Asc, and nano-sized platinum-poly(N-vinyl-pyrrolidone) colloid (PVP-Pt; 2-nm diameter) were examined on human esophagus carcinoma-derived cells KYSE70. Cell viability was repressed by 'Asc6Palm + PVP-Pt' mixture more markedly than by Asc6Palm or PVP-Pt alone, together with cell shrinkage and fragmentation, in contrast to no additive carcinostatic effect of 'Asc + PVP-Pt' or 'Asc2Phos + PVP-Pt'. The effects might be partly due to efficiency for intracellular uptake of PVP-Pt, as previously shown by our studies that Pt atoms composed of PVP-Pt were incorporated into human tongue carcinoma cells by 9.6-fold compared to normal human tongue epitheliocytes. Asc6Palm was advantageous for intracellular uptake, in terms of the proper balance for molecular hydrophilicity-lipophilicity (BMHL), whereas 6-O-stearoyl (C18) Asc or 2,6-O-dipalmitoyl (2 × C16) was demonstrated to be less carcinostatic owing to a lower BMHL. Although esterolytically converted from Asc6Palm, Asc was necessitated to be retained for efficient carcinostasis, and demonstrated by HPLC-coulometric ECD analysis to be appreciably stabilized in electrolytically generated hydrogen (dissolved hydrogen: 0.575 mg/L)-water, but scarcely in hydrogen-gas-bubbled water (0.427 mg/L), Mg stick-derived hydrogen (0.044 mg/L) water, or tap water, suggesting that hydrogen-rich water suppresses oxidative decomposition of Asc. Thus, Asc6Palm plus PVP-Pt with hydrogen-rich water supplement might be applicable for carcinostatic therapy.", "conclusion": "Although esterolytically converted from Asc6Palm, Asc was necessitated to be retained for efficient carcinostasis, and demonstrated by HPLC-coulometric ECD analysis to be appreciably stabilized in electrolytically generated hydrogen (dissolved hydrogen: 0.575 mg/L)-water, but scarcely in hydrogen-gas-bubbled water (0.427 mg/L), Mg stick-derived hydrogen (0.044 mg/L) water, or tap water, suggesting" }, { "pmid": "33368699", "year": 2021, "title": "Molecular hydrogen (H2 ) as a potential treatment for acute and chronic fatigue.", "title_en": null, "title_de": "Molekularer Wasserstoff (H₂) als potenzielle Behandlung bei akuter und chronischer Erschöpfung", "journal": "Archiv der Pharmazie", "authors": "Lucas et al.", "author_search": "lucas lucas", "doi": "10.1002/ardp.202000378", "doi_url": "https://doi.org/10.1002/ardp.202000378", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33368699/", "url": "https://h2medicine.org/studies/study-lucas-2021-acute-chronic-fatigue/", "methods": [ "unspecified" ], "indications": [ "sports-exercise", "neurology", "respiratory", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Lucas — Molecular hydrogen (H₂) as a potential treatment for acute and chronic fatigue", "summary": "This review paper argues that molecular H₂ is well-suited for treating both acute and chronic fatigue, based on the premise that oxidative stress and mitochondrial dysfunction underlie many forms of fatigue. The authors synthesise existing evidence on reactive oxygen/nitrogen species in fatigue and H₂'s antioxidant properties. This is a literature review, not a clinical trial — no new patient data are presented.", "assessment": "A plausible but still largely theoretical review. The mechanistic basis — oxidative stress drives fatigue, H₂ reduces oxidative stress — is supported by existing biology. However, this is a review paper, not a clinical trial, and the leap from antioxidant mechanism to effective fatigue treatment requires human trial evidence that remains incomplete. The authors' choice of the word „proposal“ is honest and appropriate. The review usefully collects the biological rationale across multiple fatigue contexts but should not be read as clinical proof of efficacy. A specific limitation: the heterogeneity of „fatigue“ across the diseases covered means that a single intervention may have very different effects depending on aetiology.", "abstract": "Many diseases as well as acute conditions can lead to fatigue, which can be either temporary or chronic in nature. Acute fatigue develops frequently after physical exercise or after alcohol hangover, whereas microbial infections such as influenza or COVID-19 and chronic diseases like Parkinson's disease or multiple sclerosis are often associated with chronic fatigue. Oxidative stress and a resulting disturbance of mitochondrial function are likely to be common denominators for many forms of fatigue, and antioxidant treatments have been shown to be effective in alleviating the symptoms of fatigue. In this study, we review the role of reactive oxygen and nitrogen species in fatigue and the antioxidant effects of the intake of molecular hydrogen. We propose that molecular hydrogen is well suited for the treatment of temporary and chronic forms of oxidative stress-associated fatigue.", "conclusion": "In this study, we review the role of reactive oxygen and nitrogen species in fatigue and the antioxidant effects of the intake of molecular hydrogen. We propose that molecular hydrogen is well suited for the treatment of temporary and chronic forms of oxidative stress-associated fatigue." }, { "pmid": "33246703", "year": 2021, "title": "Cobalt-modified 2D porous organic polymer for highly efficient electrocatalytic removal of toxic urea and nitrophenol.", "title_en": null, "title_de": "Kobaltmodifiziertes 2D-poröses organisches Polymer zur hocheffizienten elektrokatalytischen Entfernung von toxischem Harnstoff und Nitrophenol", "journal": "Chemosphere", "authors": "Gopi et al.", "author_search": "gopi gopi", "doi": "10.1016/j.chemosphere.2020.129052", "doi_url": "https://doi.org/10.1016/j.chemosphere.2020.129052", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33246703/", "url": "https://h2medicine.org/studies/study-gopi-2021-cobalt-modified-porous-organic/", "methods": [ "inhalation" ], "indications": [ "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2021 · Gopi — Cobalt-modified 2D porous organic polymer for highly efficient electrocatalytic removal of toxic urea and nitrophenol", "summary": "This electrochemistry study developed a cobalt-doped porous organic polymer that can efficiently catalyse the oxidation of urea and reduction of 4-nitrophenol from wastewater. Hydrogen gas appears as a by-product of the urea oxidation reaction — it is not the subject of study and has no therapeutic relevance. This is an environmental chemistry paper, not a medical study.", "assessment": "This is an environmental electrochemistry paper with no relevance to molecular H₂ as a therapeutic agent. The H₂ mentioned is a reaction by-product of electrochemical urea oxidation — a green chemistry application. No medical or biological H₂ evidence is presented. Inclusion in a medical H₂ database is an indexing artefact. The study is methodologically competent within its domain (electrocatalysis, materials science) but entirely outside the scope of hydrogen medicine.", "abstract": "The urea oxidation reaction (UOR) and nitrophenol reduction are safe and key limiting reactions for sustainable energy conversion and storage. Urea and nitrophenol are abundant in industrial and agricultural wastes, human wastewater, and in the environment. Catalytic oxidative and reductive removal is the most effective process to remove urea and 4-nitrophenol from the environment, necessary to protect human health. 2D carbon-supported, cobalt nanoparticle-based materials are emerging catalysts for nitrophenol reduction and as an anode material for the UOR. In this work, cobalt modified on a porous organic polymer (CoPOP) was synthesized and carbonized at 400 and 600 °C. The formation of CoPOP was confirmed by FT-IR spectroscopy, the 2D graphitic layer and amorphous carbon with cobalt metal by TEM, SEM, and PXRD, and the elemental composition by TEM mapping, EDX, and XPS. The catalytic activity for the 4-nitrophenol reduction was studied and the related electrocatalytic UOR was scientifically evaluated. The catalytic activity toward the reduction of 4-NP to 4-AP was tested with the addition of NaBH4; CoPOP-3 exhibited enhanced activity at a rate of 0.069 min-1. Furthermore, LSV investigated the catalytic activity of materials toward UOR, producing hydrogen gas, the products of which were analyzed via gas chromatography. Among the electrocatalysts studied, CoPOP-2 exhibited a lower onset potential, and the Tafel slope was 1.34 V and 80 mV dec-1. This study demonstrates that cobalt metal-doped porous organic polymers can be used as efficient catalysts to remove urea and nitrophenol from wastewater.", "conclusion": "Among the electrocatalysts studied, CoPOP-2 exhibited a lower onset potential, and the Tafel slope was 1.34 V and 80 mV dec-1. This study demonstrates that cobalt metal-doped porous organic polymers can be used as efficient catalysts to remove urea and nitrophenol from wastewater." }, { "pmid": "33231266", "year": 2021, "title": "Hydrogen-rich water attenuates the radiotoxicity induced by tritium exposure in vitro and in vivo.", "title_en": null, "title_de": "Wasserstoffreiches Wasser mindert die durch Tritiumexposition induzierte Radiotoxizität in vitro und in vivo", "journal": "Journal of radiation research", "authors": "Li et al.", "author_search": "li li", "doi": "10.1093/jrr/rraa104", "doi_url": "https://doi.org/10.1093/jrr/rraa104", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33231266/", "url": "https://h2medicine.org/studies/study-li-2021-attenuates-radiotoxicity-induced-tritium/", "methods": [ "drinking-hrw" ], "indications": [ "metabolic", "neurology", "cancer", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2021 · Li et al. — Hydrogen-rich water attenuates the radiotoxicity induced by tritium exposure in vitro and in vivo", "summary": "Hydrogen-rich water (HRW) reduces radioactive damage caused by tritiated water (HTO) — both in cultured human blood cells and in mice. It accelerates urinary tritium elimination, lowers tritium accumulation in tissues, and counteracts oxidative DNA damage and cell death caused by radiation. (Journal of Radiation Research, 2021.)", "assessment": "A well-designed preclinical study with a clear mechanistic hypothesis. Important limitation: this is entirely animal and cell-based research — no human data exist. The mouse dose (18.5 MBq/kg HTO) and the cell-culture conditions may not reflect realistic human radiation scenarios. The isotope-exchange mechanism (H₂ diluting ³H in body water) is biologically plausible but requires further quantification. Results cannot be directly transferred to human radioprotection without clinical follow-up studies.", "abstract": "Radionuclide tritium is widely used in the nuclear energy production industry and creates a threat to human health through radiation exposure. Herein, the radioactive elimination and radioprotective effect of hydrogen-rich water (HRW), a potential antioxidant with various medical applications, on tritiated water (HTO) exposure, was studied in vitro and in vivo. Results showed that intragastric administration of HRW effectively promoted the elimination of urinary tritium, decreased the level of serum tritium and tissue-bound tritium (OBT), and attenuated the genetic damage of blood cells in mice exposed to HTO (18.5 MBq/kg). Pretreatment with HRW effectively reduces tritium accumulation in HTO-treated human blood B lymphocyte AHH-1 cells. In addition, the anti-oxidative properties of HRW could attenuate the increased intracellular ROS (such as O2•-, •OH and ONOO-), resulting in reversing the exhaustion of cellular endogenous antioxidants (reduced GSH and SOD), decreasing lipid peroxidation (MDA), relieving DNA oxidative damage, and depressing cell apoptosis and cytotoxicity induced by HTO exposure. In conclusion, HRW is expected to be an effective radioactive elimination agent through the competition effect of isotope exchange or a radioprotective agent by scavenging free radicals induced by HTO exposure.", "conclusion": "In addition, the anti-oxidative properties of HRW could attenuate the increased intracellular ROS (such as O2•-, •OH and ONOO-), resulting in reversing the exhaustion of cellular endogenous antioxidants (reduced GSH and SOD), decreasing lipid peroxidation (MDA), relieving DNA oxidative damage, and depressing cell apoptosis and cytotoxicity induced by HTO exposure. In conclusion, HRW is expected to" }, { "pmid": "33151329", "year": 2021, "title": "Hydrogen therapy as an effective and novel adjuvant treatment against COVID-19.", "title_en": null, "title_de": "Wasserstofftherapie als wirksame und neuartige adjuvante Behandlung gegen COVID-19", "journal": "QJM : monthly journal of the Association of Physicians", "authors": "Wang et al.", "author_search": "wang wang", "doi": "10.1093/qjmed/hcaa301", "doi_url": "https://doi.org/10.1093/qjmed/hcaa301", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33151329/", "url": "https://h2medicine.org/studies/study-wang-2021-effective-adjuvant-against-covid/", "methods": [ "unspecified" ], "indications": [ "respiratory" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2021 · Wang et al. — Hydrogen therapy as an effective and novel adjuvant treatment against COVID-19", "summary": "This short theoretical commentary proposes hydrogen therapy as a potential adjuvant approach in COVID-19 treatment. No abstract or experimental data are available for this publication. The argument is based on the known anti-inflammatory and antioxidant properties of molecular hydrogen (H₂). (QJM: Monthly Journal of the Association of Physicians, 2021.)", "assessment": "This is a theoretical commentary without available abstract. No experimental data are presented here; the piece appears to argue for H₂ therapy on the basis of pre-existing mechanistic knowledge. It cannot be used as clinical evidence for H₂ efficacy against COVID-19. A companion response letter (PMID 33151328) exists, indicating this was part of an academic exchange. Interested readers should consult the full text via DOI.", "abstract": null, "conclusion": null }, { "pmid": "33151328", "year": 2021, "title": "Response to: Hydrogen therapy as an effective and novel adjuvant treatment against COVID-19.", "title_en": null, "title_de": "Antwort auf: Wasserstofftherapie als wirksame und neuartige adjuvante Behandlung gegen COVID-19", "journal": "QJM : monthly journal of the Association of Physicians", "authors": "Wang et al.", "author_search": "wang wang", "doi": "10.1093/qjmed/hcaa302", "doi_url": "https://doi.org/10.1093/qjmed/hcaa302", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33151328/", "url": "https://h2medicine.org/studies/study-wang-2021-response-effective-adjuvant-against/", "methods": [ "unspecified" ], "indications": [ "respiratory" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2021 · Wang et al. — Response to: Hydrogen therapy as an effective and novel adjuvant treatment against COVID-19", "summary": "This is a response letter to a commentary proposing hydrogen therapy in COVID-19, published in the same journal issue. No abstract is available for this letter. It represents part of an academic exchange on the theoretical rationale for H₂ in COVID-19 management. (QJM: Monthly Journal of the Association of Physicians, 2021.)", "assessment": "This is a response letter without available abstract. No experimental data are included. It cannot serve as standalone evidence for or against H₂ therapy in COVID-19. It is best understood as part of an academic debate; the original commentary (PMID 33151329) and this response should be read together via their respective DOIs.", "abstract": null, "conclusion": null }, { "pmid": "32962610", "year": 2021, "title": "Hydrogen Gas as an Exotic Performance-Enhancing Agent: Challenges and Opportunities.", "title_en": null, "title_de": "Wasserstoffgas als exotisches leistungssteigerndes Mittel: Herausforderungen und Chancen", "journal": "Current pharmaceutical design", "authors": "Ostojic", "author_search": "ostojic ostojic", "doi": "10.2174/1381612826666200922155242", "doi_url": "https://doi.org/10.2174/1381612826666200922155242", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32962610/", "url": "https://h2medicine.org/studies/study-ostojic-2021-exotic-performance-enhancing-agent/", "methods": [ "inhalation", "saline-iv", "drinking-hrw" ], "indications": [ "liver", "sports-exercise", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Ostojic — Hydrogen Gas as an Exotic Performance-Enhancing Agent: Challenges and Opportunities", "summary": "This review maps approximately two dozen studies on hydrogen (H₂) and exercise performance, finding promising ergogenic signals — but also highlighting the absence of a gold-standard protocol. H₂ — whether inhaled, drunk as hydrogen-rich water, or given intravenously — appears to benefit several exercise biomarkers, yet effect sizes are inconsistent and methodology varies widely. (Current Pharmaceutical Design, 2021.)", "assessment": "A useful overview of an emerging research niche, but several caveats apply. This is a narrative review — no meta-analysis, no pooled effect sizes. The author himself is a prominent H₂ researcher, which should be considered when reading the conclusions. The field is genuinely nascent: ~24 trials with heterogeneous designs are insufficient for definitive claims. The regulatory observation about H₂ in sport is interesting but speculative. Overall this review is informative for understanding the state of the field in 2020–2021, not for making strong efficacy claims.", "abstract": "BACKGROUND: Hydrogen gas (H2) has entered the world of experimental therapeutics approximately four and a half decades ago. Over the years, this simple molecule appears to drive more scientific attention, perhaps due to a dualism of H2 affirmative features demonstrated in numerous in vitro, animal and human studies on one side, and still puzzling mechanism(s) of its biological activity on the other. Up to this point, H2 was scrutinized for more than 170 different disease models and pathologies, and many research groups across the world have lately started to dynamically investigate its conceivable performance-enhancing potential. METHODS: We outlined here the studies indexed in leading research databases (PubMed, Web of Science, SCOPUS, JSTORE) that explored the effects of hydrogen on exercise performance, and also addressed important restraints, open questions, and windows of opportunities for forthcoming research and possible H2 enactment in exercise physiology. About two dozen trials have been identified in this domain, with most of the trials published during the past 5 years, while drinking hydrogen-rich water recognized as the most convenient method to deliver H2 in both animal and human studies. RESULTS: Either administered as an inhalational gas, enteral hydrogen-rich water, or intravenous hydrogen-rich saline, H2 seems to favorably affect various exercise performance outcomes and biomarkers of exercise-associated fatigue, inflammation, and oxidative stress. Not all studies have shown corroborative effects, and it appears that the gold-standard protocol for applying H2 in the field of exercise science does not exist at the moment, with studies markedly differ in the dose of H2 administered, the duration of treatment, and the source of hydrogen. CONCLUSION: H2 is a newfangled and rather effective performance-enhancing agent, yet its promising ergogenic potency has to be further validated and characterized in more well-controlled, appropriately sampled and longterm mechanistic trials. Also, appropriate regulation of hydrogen utilization in sport as an exotic medical gas may require distinctive legislative actions of relevant regulatory agencies in the future.", "conclusion": "H2 is a newfangled and rather effective performance-enhancing agent, yet its promising ergogenic potency has to be further validated and characterized in more well-controlled, appropriately sampled and longterm mechanistic trials. Also, appropriate regulation of hydrogen utilization in sport as an exotic medical gas may require distinctive legislative actions of relevant regulatory agencies in the future." }, { "pmid": "32954996", "year": 2021, "title": "Oxidative Stress and Pathways of Molecular Hydrogen Effects in Medicine.", "title_en": null, "title_de": "Oxidativer Stress und Wirkmechanismen von molekularem Wasserstoff in der Medizin", "journal": "Current pharmaceutical design", "authors": "Slezak et al.", "author_search": "slezak slezak", "doi": "10.2174/1381612826666200821114016", "doi_url": "https://doi.org/10.2174/1381612826666200821114016", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32954996/", "url": "https://h2medicine.org/studies/study-slezak-2021-oxidative-stress-pathways-medicine/", "methods": [ "unspecified" ], "indications": [ "metabolic", "sports-exercise", "cancer", "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Slezak et al. — Oxidative Stress and Pathways of Molecular Hydrogen Effects in Medicine", "summary": "This review explains why molecular hydrogen (H₂) has unique advantages over conventional antioxidants: it selectively neutralises the most damaging reactive oxygen species while leaving beneficial ones intact. H₂ acts not only as a direct radical scavenger but also through multiple signalling pathways — including Nrf2, NF-κB, p53, and MAPK — affecting oxidative stress, inflammation, apoptosis, and metabolism. (Current Pharmaceutical Design, 2021.)", "assessment": "A well-structured mechanistic synthesis that clearly articulates why H₂'s radical selectivity is biologically meaningful. This is a review paper — not a clinical trial. The mechanistic pathways described are plausible and supported by the primary literature cited, but establishing clinical efficacy from mechanism alone is a further step. The phrase „almost universal pluripotent therapeutic potential” is attention-grabbing; it reflects an observed pattern across many disease models, not proven clinical outcomes across all. Readers should note that H₂ effects on signalling pathways are often demonstrated in cell and animal studies — human translation requires case-by-case clinical validation.", "abstract": "There are many situations of excessive production of reactive oxygen species (ROS) such as radiation, ischemia/reperfusion (I/R), and inflammation. ROS contribute to and arises from numerous cellular pathologies, diseases, and aging. ROS can cause direct deleterious effects by damaging proteins, lipids, and nucleic acids as well as exert detrimental effects on several cell signaling pathways. However, ROS are important in many cellular functions. The injurious effect of excessive ROS can hypothetically be mitigated by exogenous antioxidants, but clinically this intervention is often not favorable. In contrast, molecular hydrogen provides a variety of advantages for mitigating oxidative stress due to its unique physical and chemical properties. H2 may be superior to conventional antioxidants, since it can selectively reduce ●OH radicals while preserving important ROS that are otherwise used for normal cellular signaling. Additionally, H2 exerts many biological effects, including antioxidation, anti-inflammation, anti-apoptosis, and anti-shock. H2 accomplishes these effects by indirectly regulating signal transduction and gene expression, each of which involves multiple signaling pathways and crosstalk. The Keap1-Nrf2-ARE signaling pathway, which can be activated by H2, plays a critical role in regulating cellular redox balance, metabolism, and inducing adaptive responses against cellular stress. H2 also influences the crosstalk among the regulatory mechanisms of autophagy and apoptosis, which involve MAPKs, p53, Nrf2, NF-κB, p38 MAPK, mTOR, etc. The pleiotropic effects of molecular hydrogen on various proteins, molecules and signaling pathways can at least partly explain its almost universal pluripotent therapeutic potential.", "conclusion": "H2 also influences the crosstalk among the regulatory mechanisms of autophagy and apoptosis, which involve MAPKs, p53, Nrf2, NF-κB, p38 MAPK, mTOR, etc. The pleiotropic effects of molecular hydrogen on various proteins, molecules and signaling pathways can at least partly explain its almost universal pluripotent therapeutic potential." }, { "pmid": "32940172", "year": 2021, "title": "Molecular Hydrogen Application in Stroke: Bench to Bedside.", "title_en": null, "title_de": "Anwendung von molekularem Wasserstoff beim Schlaganfall: Von der Forschung zur klinischen Praxis", "journal": "Current pharmaceutical design", "authors": "Huang et al.", "author_search": "huang huang", "doi": "10.2174/1381612826666200917152316", "doi_url": "https://doi.org/10.2174/1381612826666200917152316", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32940172/", "url": "https://h2medicine.org/studies/study-huang-2021-application-stroke-bench-bedside/", "methods": [ "unspecified" ], "indications": [ "neurology" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2021 · Huang et al. — Molecular Hydrogen Application in Stroke: Bench to Bedside", "summary": "This review summarises experimental and clinical evidence on molecular hydrogen (H₂) therapy in stroke, covering both animal models and human studies. The authors discuss neuroprotective mechanisms of H₂ against stroke-related brain injury and trace findings from basic research toward early clinical application. (Current Pharmaceutical Design, 2021.)", "assessment": "This is a narrative review — it summarises existing evidence rather than generating new data. The field of H₂ in stroke is scientifically interesting: H₂ can penetrate brain tissue rapidly, and its antioxidant/anti-inflammatory properties are directly relevant to ischaemia-reperfusion injury. However, the abstract is brief and does not provide specific effect sizes or study counts. Clinical trials in stroke are logistically demanding, and this review appears to cover a still-early evidence base. The „bench to bedside” framing implies potential, not proven clinical efficacy. Human data in stroke remain limited compared to preclinical literature.", "abstract": "Stroke is a major cause of mortality and morbidity worldwide. Effective treatments are limited. Molecular hydrogen is emerging as a novel medical gas with therapeutic potential for various neurological diseases, including stroke. We reviewed the experimental and clinical findings of the effects of molecular hydrogen therapy in stroke patients and models. The underlying neuroprotective mechanisms against stroke pathology were also discussed.", "conclusion": "We reviewed the experimental and clinical findings of the effects of molecular hydrogen therapy in stroke patients and models. The underlying neuroprotective mechanisms against stroke pathology were also discussed." }, { "pmid": "32632247", "year": 2021, "title": "Does drinking water rich in hydrogen gas revive brain hypometabolism in neurodegeneration by SCFAs upregulation?", "title_en": null, "title_de": "Belebt das Trinken von wasserstoffgasreichem Wasser den Hypometabolismus des Gehirns bei Neurodegeneration durch Hochregulation von SCFAs?", "journal": "European journal of clinical nutrition", "authors": "Ostojic", "author_search": "ostojic ostojic", "doi": "10.1038/s41430-020-0680-x", "doi_url": "https://doi.org/10.1038/s41430-020-0680-x", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32632247/", "url": "https://h2medicine.org/studies/study-ostojic-2021-does-drinking-revive-brain/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "neurology" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2021 · Ostojic — Does drinking water rich in hydrogen gas revive brain hypometabolism in neurodegeneration by SCFAs upregulation?", "summary": "This theoretical commentary proposes a speculative mechanism: that hydrogen-rich water (HRW) might help restore brain energy metabolism in neurodegenerative disease by increasing short-chain fatty acids (SCFAs) in the gut. No experimental data are presented; the abstract is not available in the indexed record. (European Journal of Clinical Nutrition, 2021.)", "assessment": "This is a speculative theoretical commentary without available abstract or experimental data. The proposed gut-brain-H₂ mechanism via SCFA upregulation is intellectually interesting but entirely unvalidated at this point. It should not be cited as evidence for H₂ efficacy in neurodegeneration. It is a hypothesis-generating piece that, if the mechanism is plausible, would require experimental testing in cell, animal, and eventually human models.", "abstract": null, "conclusion": null }, { "pmid": "32763820", "year": 2020, "title": "Molecular hydrogen: A potential radioprotective agent", "title_en": null, "title_de": "Molekularer Wasserstoff: Ein potenzielles Strahlenschutzmittel", "journal": "Biomedicine & Pharmacotherapy", "authors": "Hu et al.", "author_search": "hu hu", "doi": "10.1016/j.biopha.2020.110589", "doi_url": "https://doi.org/10.1016/j.biopha.2020.110589", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32763820/", "url": "https://h2medicine.org/studies/study-hu-2020-radioprotective-agent/", "methods": [ "unspecified" ], "indications": [ "oxidative-stress", "fundamentals", "cancer" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2020 · Hu — Molecular hydrogen: A potential radioprotective agent", "summary": "H₂ as a radioprotective agent: Most radiation damage arises from hydroxyl radicals (•OH) from the radiolysis of water — exactly the radical that H₂ selectively neutralizes. This review therefore sees hydrogen as a promising, novel radioprotector. (Biomedicine & Pharmacotherapy, 2020.)", "assessment": "A thematically focused review that transfers the known selectivity mechanism to a concrete field of application: protection against radiation damage. Relevant for instance in the context of collateral damage from oncological radiotherapy. For us it provides no product argument in the narrow sense, but it supports the overarching narrative of H₂ as a selective radical scavenger. Limitation, stated honestly: it is a narrative review (evidence level 4) — no original measurements, no sample, possible selection of the cited studies. The authors themselves emphasize that robust clinical evidence still needs to be developed.", "abstract": "In recent years, many studies have shown that hydrogen has therapeutic and preventive effects on various diseases. Its selective antioxidant properties were well noticed. Most of the ionizing radiation-induced damage is caused by hydroxyl radicals (OH) from radiolysis of H2O. Since hydrogen can mitigate such damage through multiple mechanisms, it presents noteworthy potential as a novel radio-protective agent. This review analyses possible mechanisms for hydrogen's radioprotective properties and effective delivery methods. We also look into details of vitro and vivo studies for hydrogen's radioprotective effects, and clinical practices. We conclude that hydrogen has good potential in radio-protection, with evidence that warrants greater research efforts in this field.", "conclusion": "We also look into details of vitro and vivo studies for hydrogen's radioprotective effects, and clinical practices. We conclude that hydrogen has good potential in radio-protection, with evidence that warrants greater research efforts in this field." }, { "pmid": "32826628", "year": 2020, "title": "Prospects of molecular hydrogen in perioperative neuroprotection from basic research to clinical application", "title_en": null, "title_de": "Perspektiven von molekularem Wasserstoff im perioperativen Nervenschutz: von der Grundlagenforschung zur klinischen Anwendung", "journal": "Current Opinion in Anaesthesiology", "authors": "Wang et al.", "author_search": "wang wang", "doi": "10.1097/aco.0000000000000915", "doi_url": "https://doi.org/10.1097/aco.0000000000000915", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32826628/", "url": "https://h2medicine.org/studies/study-wang-2020-perioperative-neuroprotection/", "methods": [ "unspecified" ], "indications": [ "neurology", "oxidative-stress", "fundamentals" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2020 · Wang — Prospects of molecular hydrogen in perioperative neuroprotection from basic research to clinical application", "summary": "This systematic review summarizes why molecular hydrogen is being researched as neuroprotection around surgery: antioxidant, anti-inflammatory, antiapoptotic and mitochondria-protective effects. Clinical efficacy, however, remains uncertain because large randomized trials are missing. (Current Opinion in Anaesthesiology, 2020 — review.)", "assessment": "A well-citable review for the mechanistic contextualization of H₂ in the neurological setting — and a model example of honest communication, because the source itself names the lack of large RCTs. Usable for us as a serious piece of evidence that the antioxidant/anti-inflammatory mechanisms of H₂ are taken seriously even in anesthesiology literature — but explicitly without a promise of patient benefit in neuroprotection. Limitation, stated honestly: it is a review (evidence level 4) and provides no original data; the statements rest predominantly on basic and animal research; clinical proof in humans is still missing per the authors themselves. The source thus clearly meets the inclusion criterion („H₂ is the clear focus“) — the entire review revolves around molecular hydrogen.", "abstract": "PURPOSE OF REVIEW: The current systematic review summarizes recent, basic clinical achievements regarding the neuroprotective effects of molecular hydrogen in distinct central nervous system conditions. RECENT FINDINGS: Perioperative neuroprotection remains a major topic of clinical anesthesia. Various gaseous molecules have previously been explored as a feasible therapeutic option in neurological disorders. Among them, molecular hydrogen, which has emerged as a novel and potential therapy for perioperative neuroprotection, has received much attention. SUMMARY: Fundamental and clinical evidence supports the antioxidant, antiinflammation, antiapoptosis and mitochondrial protective effects of hydrogen in the pathophysiology of nervous system diseases. The clinically preventive and therapeutic effects of hydrogen on different neural diseases, however, remain uncertain, and the lack of support by large randomized controlled trials has delayed its clinical application.", "conclusion": "SUMMARY: Fundamental and clinical evidence supports the antioxidant, antiinflammation, antiapoptosis and mitochondrial protective effects of hydrogen in the pathophysiology of nervous system diseases. The clinically preventive and therapeutic effects of hydrogen on different neural diseases, however, remain uncertain, and the lack of support by large randomized controlled trials has delayed its cl" }, { "pmid": "33004714", "year": 2020, "title": "Proposal of next-generation medical care \"Mega-hydrogen Therapy\".", "title_en": null, "title_de": "Vorschlag einer medizinischen Versorgung der nächsten Generation: „Mega-Wasserstoff-Therapie”", "journal": "Medical gas research", "authors": "Ichikawa et al.", "author_search": "ichikawa ichikawa", "doi": "10.4103/2045-9912.296045", "doi_url": "https://doi.org/10.4103/2045-9912.296045", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33004714/", "url": "https://h2medicine.org/studies/study-ichikawa-2020-proposal-next-generation-medical/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2020 · Ichikawa et al. — Proposal of next-generation medical care „Mega-hydrogen Therapy”", "summary": "This theoretical paper proposes the concept of „Mega-hydrogen Therapy” — delivering unusually high doses of molecular hydrogen (H₂) — as a next-generation medical approach. No abstract or experimental data are available for this publication. (Medical Gas Research, 2020.)", "assessment": "This is a theoretical proposal without available abstract or experimental data. „Mega-hydrogen Therapy” as a concept is not yet supported by published clinical trials. This piece should be treated as a hypothesis or perspective, not as evidence of efficacy. Interested readers should consult the full text to assess the authors' reasoning and referenced preclinical basis.", "abstract": null, "conclusion": null }, { "pmid": "32729851", "year": 2020, "title": "Catalytic reductive aminations using molecular hydrogen for synthesis of different kinds of amines.", "title_en": null, "title_de": "Katalytische reduktive Aminierungen unter Verwendung von molekularem Wasserstoff zur Synthese verschiedener Arten von Aminen", "journal": "Chemical Society reviews", "authors": "Murugesan et al.", "author_search": "murugesan murugesan", "doi": "10.1039/c9cs00286c", "doi_url": "https://doi.org/10.1039/c9cs00286c", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32729851/", "url": "https://h2medicine.org/studies/study-murugesan-2020-catalytic-reductive-aminations-synthesis/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2020 · Murugesan et al. — Catalytic reductive aminations using molecular hydrogen for synthesis of different kinds of amines", "summary": "This is an organic chemistry review on industrial and pharmaceutical amine synthesis using molecular hydrogen as a reducing agent — it has no connection to hydrogen therapy or medical use of H₂ in the human body. Molecular hydrogen here functions as a chemical reagent in catalytic reactions, not as a biomedical agent. (Chemical Society Reviews, 2020.)", "assessment": "This paper is outside the scope of hydrogen medicine. It is a chemistry review on catalytic reductive amination and does not provide evidence for or against therapeutic H₂ use. It should not be cited in the context of hydrogen therapy research. Its inclusion in this database is likely a false positive due to keyword overlap with „molecular hydrogen”.", "abstract": "Reductive aminations constitute an important class of reactions widely applied in research laboratories and industries for the synthesis of amines as well as pharmaceuticals, agrochemicals and biomolecules. In particular, catalytic reductive aminations using molecular hydrogen are highly valued and essential for the cost-effective and sustainable production of different kinds of amines and their functionalization. These reactions couple easily accessible carbonyl compounds (aldehydes or ketones) with ammonia, amines or nitro compounds in the presence of suitable catalysts and hydrogen that enable the preparation of linear and branched primary, secondary and tertiary amines including N-methylamines and molecules used in life science applications. In general, amines represent valuable fine and bulk chemicals, which serve as key precursors and central intermediates for the synthesis of advanced chemicals, life science molecules, dyes and polymers. Noteworthily, amine functionalities are present in a large number of pharmaceuticals, agrochemicals and biomolecules, and play vital roles in the function of these active compounds. In general, reductive aminations are challenging processes, especially for the syntheses of primary amines, which often are non-selective and suffer from over-alkylation and reduction of carbonyl compounds to the corresponding alcohols. Hence, the development of suitable catalysts to perform these reactions in a highly efficient and selective manner is crucial and continues to be important and attracts scientific interest. In this regard, both homogeneous and heterogeneous catalysts have successfully been developed for these reactions to access various amines. There is a need for a comprehensive review on catalytic reductive aminations to discuss the potential catalysts used and applicability of this methodology in the preparation of different kinds of amines, which are of commercial, industrial and medicinal importance. Consequently, in this review we discuss catalytic reductive aminations using molecular hydrogen and their applications in the synthesis of functionalized and structurally diverse benzylic, heterocyclic and aliphatic primary, secondary and tertiary amines as well as N-methylamines and more complex drug targets. In addition, mechanisms of reductive aminations including selective formation of desired amine products as well as possible side reactions are emphasized. This review aims at the scientific communities working in the fields of organic synthesis, catalysis, and medicinal and biological chemistry.", "conclusion": "In addition, mechanisms of reductive aminations including selective formation of desired amine products as well as possible side reactions are emphasized. This review aims at the scientific communities working in the fields of organic synthesis, catalysis, and medicinal and biological chemistry." }, { "pmid": "32189669", "year": 2020, "title": "A \"philosophical molecule,\" hydrogen may overcome senescence and intractable diseases.", "title_en": null, "title_de": "Ein „philosophisches Molekül“: Wasserstoff könnte Seneszenz und hartnäckige Erkrankungen überwinden", "journal": "Medical gas research", "authors": "Hirano et al.", "author_search": "hirano hirano", "doi": "10.4103/2045-9912.279983", "doi_url": "https://doi.org/10.4103/2045-9912.279983", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32189669/", "url": "https://h2medicine.org/studies/study-hirano-2020-philosophical-molecule-may-overcome/", "methods": [ "inhalation" ], "indications": [ "sports-exercise", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2020 · Hirano et al. — A „philosophical molecule,” hydrogen may overcome senescence and intractable diseases", "summary": "This short review argues that molecular hydrogen (H₂) is uniquely positioned to combat ageing and difficult-to-treat diseases by scavenging hydroxyl radicals (·OH) — the most damaging reactive oxygen species — which are predominantly generated in the mitochondria. H₂ is proposed as the only molecule that can both penetrate mitochondria and neutralise ·OH. (Medical Gas Research, 2020.)", "assessment": "This is a narrative review with strong theoretical claims. The biochemical premise — that ·OH is central to oxidative cell damage, and that H₂ selectively neutralises it — is supported by the literature. However, the claim that H₂ can „overcome senescence and intractable diseases” is a broad extrapolation that goes significantly beyond available clinical evidence. No human trial data are cited in support of these claims. This paper should be read as a theoretical position piece, not as evidence for clinical H₂ efficacy in ageing or specific diseases.", "abstract": "It has been revealed that the cause of senescence and diseases is associated with the reactive oxygen species \"hydroxyl radicals\" (·OH). Senescence and diseases may be overcome as long as we can scavenge •OH mostly produced in mitochondria. It is one and only one \"molecular hydrogen\" (H2) that can both penetrate into the mitochondria and scavenge the •OH. The H2 in the body can function in disease prevention and recovery. H2 gas is explosive so that a safe hydrogen inhaler has to be developed for home use. We would like to advocate the great use of H2.", "conclusion": "H2 gas is explosive so that a safe hydrogen inhaler has to be developed for home use. We would like to advocate the great use of H2." }, { "pmid": "32097610", "year": 2020, "title": "The future of cryoablation: An abscopal effect.", "title_en": null, "title_de": "Die Zukunft der Kryoablation: Ein abskopaler Effekt", "journal": "Cryobiology", "authors": "Chen et al.", "author_search": "chen chen", "doi": "10.1016/j.cryobiol.2020.02.010", "doi_url": "https://doi.org/10.1016/j.cryobiol.2020.02.010", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32097610/", "url": "https://h2medicine.org/studies/study-chen-2020-future-cryoablation-abscopal/", "methods": [ "inhalation" ], "indications": [ "cancer", "immune-system" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2020 · Chen et al. — The future of cryoablation: An abscopal effect", "summary": "This review on cryoablation for cancer treatment briefly mentions molecular hydrogen (H₂) as a potential combination partner — specifically because H₂ may rescue exhausted CD8+ T cells and thereby amplify the immune response triggered by tumour ablation. H₂ is not the main subject of this paper but appears as one of several proposed combination strategies. (Cryobiology, 2020.)", "assessment": "This is a narrative review on cryoablation, not on hydrogen therapy per se. The H₂-related content is a brief supporting reference in the context of combination immuno-oncology strategies. The cited H₂ data appear to come from a single oncology study (advanced colorectal cancer) and the proposed mechanism (PGC-1α / CD8+ T cell rescue) is not yet established as a general principle. This paper is relevant to H₂ in oncology as a secondary reference, not as direct evidence of H₂ efficacy.", "abstract": "Cryoablation has become a popular modality to treat a variety of malignant tumors in solid organs and soft tissues. In the future, the use of cryoablation should focus on its abscopal effect. The present review discusses the increased immune response triggered by cryoablation alone or by cryoablation combined with immunotherapies, which can improve the immune response and limit immunosuppression. First, cryoablative techniques should be improved to increase the area of necrosis and reduce the area of apoptosis. Second, cryoablation should be combined with immunotherapies, for example, cyclophosphamide, natural killer cells, granulocyte monocyte colony stimulating factor (GM-CSF), cytotoxic T lymphocyte-associated antigen (CTLA)-4, and programmed death receptor 1 (PD)-1 inhibitors. Cryoablation could also be combined with Hydrogen gas molecules, which were shown recently to stimulate peroxisome proliferator activated receptor gamma coactivator (PGC)-1α, thereby promoting mitochondrial function, which might rescue exhausted CD8+ T cells, leading to prolonged progression-free survival and overall survival of patients with advanced colorectal cancer.", "conclusion": "Second, cryoablation should be combined with immunotherapies, for example, cyclophosphamide, natural killer cells, granulocyte monocyte colony stimulating factor (GM-CSF), cytotoxic T lymphocyte-associated antigen (CTLA)-4, and programmed death receptor 1 (PD)-1 inhibitors. Cryoablation could also be combined with Hydrogen gas molecules, which were shown recently to stimulate peroxisome proliferat" }, { "pmid": "32015786", "year": 2020, "title": "Application of Molecular Hydrogen as a Novel Antioxidant in Sports Science.", "title_en": null, "title_de": "Anwendung von molekularem Wasserstoff als neuartiges Antioxidans in der Sportwissenschaft", "journal": "Oxidative medicine and cellular longevity", "authors": "Kawamura et al.", "author_search": "kawamura kawamura", "doi": "10.1155/2020/2328768", "doi_url": "https://doi.org/10.1155/2020/2328768", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32015786/", "url": "https://h2medicine.org/studies/study-kawamura-2020-application-antioxidant-sports-science/", "methods": [ "inhalation", "bath-topical", "drinking-hrw" ], "indications": [ "diabetes", "sports-exercise", "neurology", "cancer", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2020 · Kawamura et al. — Application of Molecular Hydrogen as a Novel Antioxidant in Sports Science", "summary": "This review surveys the evidence on molecular hydrogen (H₂) intake and exercise, covering all administration routes and focusing on exercise-induced oxidative stress. Only six studies had been published on H₂ and exercise at the time; the review provides a summary of physiological and biochemical findings and highlights the need for more research. (Oxidative Medicine and Cellular Longevity, 2020.)", "assessment": "A transparent and appropriately cautious review. With only six studies available, no strong conclusions can be drawn. The authors are clear about this limitation. The theoretical rationale for H₂ in exercise (selective ·OH scavenging without blunting beneficial ROS signalling) is scientifically interesting and distinct from generic antioxidant supplementation. The review covers diseases (cancer, diabetes, brain injury) in passing, but the core focus is sports science. Since 2020, the exercise H₂ literature has grown, but a definitive evidence base remains under construction.", "abstract": "Molecular hydrogen (H2) is a colorless, tasteless, odorless, and minimal molecule with high flammability. Although H2 has been thought to be an inert gas in living bodies for many years, an animal study reported that inhalation of H2 gas decreased oxidative stress and suppressed brain injury caused by ischemia and reperfusion injury due to its antioxidant action. Since then, the antioxidant action of H2 has attracted considerable attention and many studies have reported on its benefits. Most studies have reported the effects of H2 on diseases such as cancer, diabetes, cerebral infarction, and Alzheimer's disease. However, little is known regarding its effects on healthy subjects and exercise. Thus far, including our study, only 6 studies have explored the effect of H2 on exercise. H2 is the smallest molecule and therefore can easily penetrate the cellular membrane and rapidly diffuse into organelles. H2 is thought to be able to selectively reduce hydroxyl radicals and peroxynitrite and does not affect physiologically reactive species. H2 can be supplied to the body through multiple routes of administration, such as oral intake of H2 water and H2 bathing. Therefore, H2 may be a potential alternative strategy for conventional exogenous antioxidant interventions in sports science. The purpose of this review is to provide evidence regarding the effects of H2 intake on changes in physiological and biochemical parameters, centering on exercise-induced oxidative stress, for each intake method. Furthermore, this review highlights possible future directions in this area of research.", "conclusion": "The purpose of this review is to provide evidence regarding the effects of H2 intake on changes in physiological and biochemical parameters, centering on exercise-induced oxidative stress, for each intake method. Furthermore, this review highlights possible future directions in this area of research." }, { "pmid": "31996394", "year": 2020, "title": "Molecular Hydrogen Metabolism: a Widespread Trait of Pathogenic Bacteria and Protists.", "title_en": null, "title_de": "Stoffwechsel von molekularem Wasserstoff: ein weit verbreitetes Merkmal pathogener Bakterien und Protisten", "journal": "Microbiology and molecular biology reviews : MMBR", "authors": "Benoit et al.", "author_search": "benoit benoit", "doi": "10.1128/mmbr.00092-19", "doi_url": "https://doi.org/10.1128/mmbr.00092-19", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31996394/", "url": "https://h2medicine.org/studies/study-benoit-2020-metabolism-widespread-trait-pathogenic/", "methods": [ "drinking-hrw" ], "indications": [ "metabolic", "sports-exercise", "respiratory", "womens-health" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2020 · Benoit — Molecular Hydrogen Metabolism: a Widespread Trait of Pathogenic Bacteria and Protists", "summary": "Over 200 known pathogens carry genes for hydrogenases — enzymes that let bacteria consume or produce H₂ gas as part of their energy metabolism. This comprehensive review shows that several major human pathogens, including Salmonella, Campylobacter, and Helicobacter pylori, exploit the large amounts of H₂ produced by the gut microbiome as a respiratory energy source — a trait that supports their growth and virulence. The authors also explore H₂ metabolism as a potential drug target. (Microbiology and Molecular Biology Reviews, 2020.)", "assessment": "This is a review article, not a clinical study. It synthesises existing literature on microbial H₂ metabolism — it does not test therapeutic hydrogen in humans or animals. The coverage is impressive in breadth, but the authors openly acknowledge that detailed mechanistic understanding is still lacking for most pathogens, especially obligate anaerobes. The proposal to use H₂ metabolism as a drug target is an early-stage hypothesis, not an established therapeutic avenue. Readers looking for evidence of H₂ supplementation benefits in humans will not find that here — the focus is on pathogen biology, not on therapeutic hydrogen for the host.", "abstract": "Pathogenic microorganisms use various mechanisms to conserve energy in host tissues and environmental reservoirs. One widespread but often overlooked means of energy conservation is through the consumption or production of molecular hydrogen (H2). Here, we comprehensively review the distribution, biochemistry, and physiology of H2 metabolism in pathogens. Over 200 pathogens and pathobionts carry genes for hydrogenases, the enzymes responsible for H2 oxidation and/or production. Furthermore, at least 46 of these species have been experimentally shown to consume or produce H2 Several major human pathogens use the large amounts of H2 produced by colonic microbiota as an energy source for aerobic or anaerobic respiration. This process has been shown to be critical for growth and virulence of the gastrointestinal bacteria Salmonella enterica serovar Typhimurium, Campylobacter jejuni, Campylobacter concisus, and Helicobacter pylori (including carcinogenic strains). H2 oxidation is generally a facultative trait controlled by central regulators in response to energy and oxidant availability. Other bacterial and protist pathogens produce H2 as a diffusible end product of fermentation processes. These include facultative anaerobes such as Escherichia coli, S Typhimurium, and Giardia intestinalis, which persist by fermentation when limited for respiratory electron acceptors, as well as obligate anaerobes, such as Clostridium perfringens, Clostridioides difficile, and Trichomonas vaginalis, that produce large amounts of H2 during growth. Overall, there is a rich literature on hydrogenases in growth, survival, and virulence in some pathogens. However, we lack a detailed understanding of H2 metabolism in most pathogens, especially obligately anaerobic bacteria, as well as a holistic understanding of gastrointestinal H2 transactions overall. Based on these findings, we also evaluate H2 metabolism as a possible target for drug development or other therapies.", "conclusion": "However, we lack a detailed understanding of H2 metabolism in most pathogens, especially obligately anaerobic bacteria, as well as a holistic understanding of gastrointestinal H2 transactions overall. Based on these findings, we also evaluate H2 metabolism as a possible target for drug development or other therapies." }, { "pmid": "31675478", "year": 2020, "title": "Acute ingestion of hydrogen-rich water does not improve incremental treadmill running performance in endurance-trained athletes", "title_en": null, "title_de": "Die akute Einnahme von wasserstoffreichem Wasser verbessert die ansteigende Laufleistung auf dem Laufband bei ausdauertrainierten Athleten nicht", "journal": "Applied Physiology, Nutrition, and Metabolism", "authors": "Ooi et al.", "author_search": "ooi ooi", "doi": "10.1139/apnm-2019-0553", "doi_url": "https://doi.org/10.1139/apnm-2019-0553", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31675478/", "url": "https://h2medicine.org/studies/study-ooi-2020-treadmill-running-endurance-athletes/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2020 · Ooi — Acute ingestion of hydrogen-rich water does not improve incremental treadmill running performance in endurance-trained athletes", "summary": "A single serving of hydrogen water shortly before the run brought no performance gain. In 14 endurance-trained runners, time to exhaustion, maximal oxygen uptake and perceived exertion did not differ from placebo. An honest null finding. (Appl Physiol Nutr Metab, 2020.)", "assessment": "Deliberately included as an honest null finding — this strengthens the credibility of the whole database. The study is methodologically sound: a double-blind, placebo-controlled crossover design, each participant is their own control. The central lesson for us: a single small dose (2 × 290 ml) shortly before exercise is not enough for an ergogenic effect in already well-trained athletes. This is not an argument against H₂ in sport generally, but for realistic expectations and suitable protocols — other works (Mikami 2019, Botek 2019) found positive effects with different doses/designs, as did the two-week continuous use in Hori et al. Limitations, stated honestly: small sample (n = 14), only male, already fully trained runners (low room for improvement), and a low single dose.", "abstract": "There is emerging evidence that hydrogen-rich water (H2-water) has beneficial effects on the physiological responses to exercise. However, few studies investigate its ergogenic potential. This randomized controlled trial examined the effects of H2-water ingestion on physiological responses and exercise performance during incremental treadmill running. In a double-blind crossover design, 14 endurance-trained male runners (age, 34 ± 4 years; body mass, 63.1 ± 7.2 kg; height, 1.72 ± 0.05 m) were randomly assigned to ingest 2 doses of 290-mL H2-water or placebo on each occasion. The first bolus was given before six 4-min submaximal running bouts, and the second bolus was consumed before the maximal incremental running test. Expired gas, heart rate (HR), and ratings of perceived exertion (RPE) were recorded; blood samples were collected at the end of each submaximal stage and post maximal running test. Cardiorespiratory responses, RPE, and blood gas indices were not significantly different at each submaximal running intensity (range: 34%-91% maximal oxygen uptake) between H2-water and placebo trials. No statistical difference was observed in running time to exhaustion (618 ± 126 vs. 619 ± 113 s), maximal oxygen uptake (56.9 ± 4.4 vs. 57.1 ± 4.7 mL·kg-1·min-1), maximal HR (184 ± 7 vs. 184 ± 7 beat·min-1), and RPE (19 ± 1 vs. 19 ± 1) in the runners between the trials. The results suggest that the ingestion of 290 mL of H2-water before submaximal treadmill running and an additional dose before the subsequent incremental running to exhaustion were not sufficiently ergogenic in endurance-trained athletes. Novelty Acute ingestion of H2-water does not seem to be ergogenic for endurance performance. A small dose of H2-water does not modulate buffering capacity during intense endurance exercise in athletes.", "conclusion": "Novelty Acute ingestion of H2-water does not seem to be ergogenic for endurance performance. A small dose of H2-water does not modulate buffering capacity during intense endurance exercise in athletes." }, { "pmid": "32470022", "year": 2020, "title": "Peripheral endothelial function can be improved by daily consumption of water containing over 7 ppm of dissolved hydrogen: A randomized controlled trial", "title_en": null, "title_de": "Die periphere Endothelfunktion kann durch den täglichen Konsum von Wasser mit über 7 ppm gelöstem Wasserstoff verbessert werden: Eine randomisierte kontrollierte Studie", "journal": "PLoS One", "authors": "Ishibashi et al.", "author_search": "ishibashi ishibashi", "doi": "10.1371/journal.pone.0233484", "doi_url": "https://doi.org/10.1371/journal.pone.0233484", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32470022/", "url": "https://h2medicine.org/studies/study-ishibashi-2020-peripheral-endothelial-function-7ppm/", "methods": [ "drinking-hrw" ], "indications": [ "cardiovascular", "oxidative-stress" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2020 · Ishibashi — Peripheral endothelial function can be improved by daily consumption of water containing over 7 ppm of dissolved hydrogen: A randomized controlled trial", "summary": "Highly concentrated hydrogen water (over 7 ppm) improves the endothelial function of the small arteries. In a randomized controlled trial (n = 68), the reactive hyperemia index rose by 22.2% as soon as 24 hours after the first intake and by 25.4% after two weeks of daily drinking (p (PLoS One, 2020.)", "assessment": "One of the most directly relevant studies for H₂ drinking-water research: it measures an established cardiovascular early marker (endothelial function) and shows a clear, fast effect already after 24 hours. Especially notable is the explicit dose threshold of over 7 ppm — this indicates why a high hydrogen concentration matters and that lower concentrations may not deliver the same effect. It is a real RCT with placebo (N₂ water), which increases its informative value. Limitations, stated honestly: the participants were healthy (no patients with established vascular disease), the sample of n = 68 is moderate, and the abstract gives no information on possible conflicts of interest of the company that produced the water. The measured endpoint is a surrogate marker, not a clinical event like a heart attack.", "abstract": "BACKGROUND: Measurement of the reactive hyperemia index (RHI) using peripheral arterial tonometry (PAT) has shown benefits in the evaluation of vascular endothelial function and prediction of cardiovascular disease prognosis. Thus, it is important to examine the factors that promote the RHI. In this study, we aimed to investigate the effect of molecular hydrogen (H2) on reactive hyperemia-PAT of the small arteries of fingers in healthy people. METHODS: To determine the efficacy of H2 for improving peripheral vascular endothelial function, water containing high H2 concentrations was administered to participants, and the Ln_RHI was measured in the finger vasculature. Sixty-eight volunteers were randomly divided into two groups: a placebo group (n = 34) that drank molecular nitrogen (N2)-containing water and a high H2 group (n = 34) that drank high H2 water (containing 7 ppm of H2: 3.5 mg H2 in 500-mL water). The Ln_RHI was measured before ingesting the placebo or high H2 water, 1 h and 24 h after the first ingestion, and 14 days after daily ingestion of high H2 water or the placebo. The mixed effects model for repeated measures was used in data analysis. RESULTS: The high H2 group had a significantly greater improvement in Ln_RHI than the placebo group. Ln_RHI improved by 22.2% (p<0.05) at 24 h after the first ingestion of high H2 water and by 25.4% (p<0.05) after the daily consumption of high H2 water for 2 weeks. CONCLUSIONS: Daily consumption of high H2 water improved the endothelial function of the arteries or arterioles assessed by the PAT test. The results suggest that the continuous consumption of high H2 water contributes to improved cardiovascular health.", "conclusion": "Daily consumption of high H2 water improved the endothelial function of the arteries or arterioles assessed by the PAT test. The results suggest that the continuous consumption of high H2 water contributes to improved cardiovascular health." }, { "pmid": "32699287", "year": 2020, "title": "Hydrogen-rich water reduces inflammatory responses and prevents apoptosis of peripheral blood cells in healthy adults: a randomized, double-blind, controlled trial", "title_en": null, "title_de": "Wasserstoffreiches Wasser reduziert Entzündungsreaktionen und verhindert die Apoptose peripherer Blutzellen bei gesunden Erwachsenen: eine randomisierte, doppelblinde, kontrollierte Studie", "journal": "Scientific Reports", "authors": "Sim et al.", "author_search": "sim sim", "doi": "10.1038/s41598-020-68930-2", "doi_url": "https://doi.org/10.1038/s41598-020-68930-2", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32699287/", "url": "https://h2medicine.org/studies/study-sim-2020-inflammatory-responses-apoptosis-blood-cells/", "methods": [ "drinking-hrw" ], "indications": [ "oxidative-stress", "fundamentals", "metabolic" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2020 · Sim — Hydrogen-rich water reduces inflammatory responses and prevents apoptosis of peripheral blood cells in healthy adults: a randomized, double-blind, controlled trial", "summary": "Hydrogen-rich water dampens inflammatory responses and protects blood cells from cell death — in healthy adults. In a randomized double-blind design (38 participants, 1.5 L/day, 4 weeks), inflammatory and NF-κB signaling pathways were significantly down-regulated and apoptosis of immune cells markedly lower. (Scientific Reports, 2020 — with RNA sequencing as molecular evidence.)", "assessment": "Notable for the question of inflammation and immune function because here not only an effect is measured but a molecular mechanism (NF-κB down-regulation, less apoptosis) is shown in healthy people — and that in a double-blind, controlled design in an established journal (Scientific Reports). This fits the mechanistic picture of „prevention and wellbeing“, not just „disease treatment“. Limitation, stated honestly: small sample (n = 38), healthy subjects (no disease endpoint), only 4 weeks, and the classic oxidation markers (BAP, dROM, 8-OHdG) did not differ in the overall cohort — the benefit only appeared in subgroups (≥ 30 years) and at the molecular level.", "abstract": "The evidence for the beneficial effects of drinking hydrogen-water (HW) is rare. We aimed to investigate the effects of HW consumption on oxidative stress and immune functions in healthy adults using systemic approaches of biochemical, cellular, and molecular nutrition. In a randomized, double-blind, placebo-controlled study, healthy adults (20-59 y) consumed either 1.5 L/d of HW (n = 20) or plain water (PW, n = 18) for 4 weeks. The changes from baseline to the 4th week in serum biological antioxidant potential (BAP), derivatives of reactive oxygen, and 8-Oxo-2'-deoxyguanosine did not differ between groups; however, in those aged ≥ 30 y, BAP increased greater in the HW group than the PW group. Apoptosis of peripheral blood mononuclear cells (PBMCs) was significantly less in the HW group. Flow cytometry analysis of CD4+, CD8+, CD20+, CD14+ and CD11b+ cells showed that the frequency of CD14+ cells decreased in the HW group. RNA-sequencing analysis of PBMCs demonstrated that the transcriptomes of the HW group were clearly distinguished from those of the PW group. Most notably, transcriptional networks of inflammatory responses and NF-κB signaling were significantly down-regulated in the HW group. These finding suggest HW increases antioxidant capacity thereby reducing inflammatory responses in healthy adults.", "conclusion": "Most notably, transcriptional networks of inflammatory responses and NF-κB signaling were significantly down-regulated in the HW group. These finding suggest HW increases antioxidant capacity thereby reducing inflammatory responses in healthy adults." }, { "pmid": "33380581", "year": 2020, "title": "Impact of hydrogen-rich gas mixture inhalation through nasal cannula during post-exercise recovery period on subsequent oxidative stress, muscle damage, and exercise performances in men", "title_en": null, "title_de": "Auswirkungen der Inhalation eines wasserstoffreichen Gasgemischs über eine Nasenkanüle während der Erholungsphase nach dem Sport auf den nachfolgenden oxidativen Stress, die Muskelschädigung und die sportlichen Leistungen bei Männern", "journal": "Medical Gas Research", "authors": "Shibayama et al.", "author_search": "shibayama shibayama", "doi": "10.4103/2045-9912.304222", "doi_url": "https://doi.org/10.4103/2045-9912.304222", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33380581/", "url": "https://h2medicine.org/studies/study-shibayama-2020-nasal-cannula-post-exercise-recovery-muscle-damage/", "methods": [ "inhalation", "bath-topical" ], "indications": [ "sports-exercise", "oxidative-stress" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2020 · Shibayama — Impact of hydrogen-rich gas mixture inhalation through nasal cannula during post-exercise recovery period on subsequent oxidative stress, muscle damage, and exercise performances in men", "summary": "Inhaling hydrogen gas right after intense exercise lowered a DNA oxidation marker and protected jump strength from the exercise-induced drop. Other performance and blood markers, however, remained unchanged. (Medical Gas Research, 2020, double-blind, crossover, n = 8.)", "assessment": "Interesting for H₂ inhalation applications in sports recovery. The study is a good example of honest communication: there is a plausible, significant effect on oxidative DNA stress and one performance aspect — but not on the full range of markers. One should not derive a „H₂ makes you fit faster“ claim from this. Limitation, stated honestly: very small sample (n = 8), multiple comparisons (the risk that individual significances are chance hits is real), and the protective effect only concerned one of several performance tests. Mechanistically the finding (less 8-OHdG) fits the known antioxidant profile of H₂. It complements the mixed picture of the sports evidence in this batch.", "abstract": "Molecular hydrogen has been suggested to have a cytoprotective effect on the whole body and to enhance exercise performances. However, the effect of hydrogen-rich gas mixture (HG) inhalation on physiological responses has been poorly investigated. We examined the impact of acute HG inhalation on subsequent oxidative stress, muscle damage, and exercise performances during the recovery period after a strenuous exercise. This is a two-trial, double-blind, crossover, repeated measures study. Eight physically active male volunteers inhaled HG (estimated fraction of inspired oxygen and hydrogen were 21.57 and 4.08% at most, respectively) or normal gas (placebo, ambient air 400 m above sea level) during a 60-minute recovery phase after oxidative stress-inducing exercise) completion comprising 30-minute treadmill running at an intensity corresponding to 75% of maximal oxygen uptake and squat jumps (5 sets × 10 repetitions). Before oxidative stress-inducing exercise and 10 minutes after the post-exercise gas inhalation, blood and urine samples were obtained and exercise performances (jumping ability; pedaling power output; muscle strength) were evaluated. Post-exercise HG inhalation attenuated the increase in urinary 8-hydroxydeoxyguanosine excretion rate (P < 0.05), a DNA oxidation marker, and the reduction in the countermovement jump height (P < 0.05), compared with Placebo inhalation. Other exercise performances and blood oxidative stress and muscle damage markers did not differ between HG and Placebo inhalation. Moreover, the increase in urinary 8-hydroxydeoxyguanosine excretion rate was significantly associated with countermovement jump performance reduction (r = -0.78, P < 0.01). These findings suggested that HG inhalation during post-exercise recovery period might improve exercise performance via reducing systemic oxidative damage. The study was approved by the Human Research Ethics Committee of the University of Yamanashi (approval No. H29-006) on June 28, 2017.", "conclusion": "The study was approved by the Human Research Ethics Committee of the University of Yamanashi (approval No. H29-006) on June 28, 2017." }, { "pmid": "33380582", "year": 2020, "title": "Two-week continuous supplementation of hydrogen-rich water increases peak oxygen uptake during an incremental cycling exercise test in healthy humans: a randomized, single-blinded, placebo-controlled study", "title_en": null, "title_de": "Eine zweiwöchige kontinuierliche Supplementierung mit wasserstoffreichem Wasser erhöht die maximale Sauerstoffaufnahme während eines ansteigenden Radergometer-Belastungstests bei gesunden Menschen: eine randomisierte, einfach-verblindete, placebokontrollierte Studie", "journal": "Medical Gas Research", "authors": "Hori et al.", "author_search": "hori hori", "doi": "10.4103/2045-9912.304223", "doi_url": "https://doi.org/10.4103/2045-9912.304223", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33380582/", "url": "https://h2medicine.org/studies/study-hori-2020-peak-oxygen-uptake-cycling-test/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise", "metabolic" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2020 · Hori — Two-week continuous supplementation of hydrogen-rich water increases peak oxygen uptake during an incremental cycling exercise test in healthy humans: a randomized, single-blinded, placebo-controlled study", "summary": "Two weeks of daily hydrogen-rich water significantly increased peak oxygen uptake (VO₂peak) in healthy people in the cycle ergometer test. A single serving, by contrast, brought no measurable effect — the benefit only emerges with continuous intake. (Medical Gas Research, 2020, randomized, single-blinded, placebo-controlled.)", "assessment": "Relevant to aerobic capacity in endurance and fitness training — and especially valuable because it provides an honest differentiation: continuous intake beats the quick „pre-workout sip“. This points to continuous daily intake rather than a single dose as the effective regimen, and it also debunks the expectation that a single sip before a competition delivers instant performance. Limitation, stated honestly: small number of subjects, only single-blinded (bias possible in a will-dependent exhaustion test), and the mechanism remains open since oxidative stress and antioxidants did not change. It fits thematically with the other sports studies on this topic, which show a mixed picture.", "abstract": "The various beneficial effects of the intake of molecular hydrogen (H2) have been demonstrated in the field of sports science. Although supplementation of H2 has been reported to increase mitochondrial metabolism in animal studies, the effects of the administration of H2 on aerobic capacity during exercise in humans are still not clear. We investigated whether a single or 2-week continuous intake of H2-rich water (HW) enhanced the aerobic capacity during incremental exercise in healthy humans. In this randomized, single-blinded, placebo-controlled experimental study, the participants performed an incremental cycling exercise to measure peak oxygen uptake and peak load before and after a single (500 mL) or a 2-week supplementation (total 5 L) of HW. In the latter experiment, the participants drank the 500 mL of HW on all weekdays (i.e., 10 times). The single intake of HW did not significantly increase peak oxygen uptake and peak load, and did not significantly alter the responses in oxidative stress, antioxidant activity, and lactate levels. However, importantly, the 2-week continuous consumption of HW significantly augmented peak oxygen uptake and tended to increase the peak load without any significant changes in lactate levels, oxidative stress, and antioxidant responses. In conclusion, the continuous supplementation of HW potentially augments the aerobic capacity, implying that continuous supplementation of H2 might help improve aerobic exercise performance and physical health. This study protocol was approved by the Ethical Committee of Chubu University (approval No. 260086-2) on March 29, 2018.", "conclusion": "This study protocol was approved by the Ethical Committee of Chubu University (approval No. 260086-2) on March 29, 2018." }, { "pmid": "32791592", "year": 2020, "title": "[Changes of nasal nitric oxide in the treatment of allergic rhinitis with hydrogen-rich saline lavage of nasal cavity].", "title_en": null, "title_de": "Veränderungen des nasalen Stickstoffmonoxids bei der Behandlung der allergischen Rhinitis mit wasserstoffreicher Nasenspülung", "journal": "Lin chuang er bi yan hou tou jing wai ke za zhi (Journal of Clinical Otorhinolaryngology Head and Neck Surgery)", "authors": "Jin et al.", "author_search": "jin jin", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32791592/", "url": "https://h2medicine.org/studies/study-jin-2020-allergic-rhinitis-nasal-saline-lavage/", "methods": [ "saline-iv", "bath-topical" ], "indications": [ "allergy", "respiratory" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2020 · Jin — Changes of nasal nitric oxide in the treatment of allergic rhinitis with hydrogen-rich saline lavage of nasal cavity", "summary": "A nasal lavage with hydrogen-rich saline significantly changed the nitric-oxide value in the nose and could thus offer a starting point for treating allergic rhinitis (hay fever). A small, randomized, double-blind self-controlled study with 20 patients. (J Clin Otorhinolaryngol Head Neck Surg, 2020.)", "assessment": "Notable as an example of a topical H₂ application (nasal lavage) beyond drinking and inhalation — allergic rhinitis is a very common complaint. The strength of evidence is limited, however: this is a pilot study with only 20 participants, the primary endpoint is a biomarker (nasal NO), not a clearly measured clinical symptom score over the season. The contribution is in a foreign language (Chinese) and has no DOI, which makes it harder to find. Useful as supporting evidence for an anti-inflammatory H₂ principle at the nasal mucosa, not as solid proof of efficacy. Mechanistically the finding fits the preclinical Niu study, where H₂ dampens allergic inflammation in the animal model.", "abstract": "Objective:To observe the effect of hydrogen-rich saline on the concentration of nitric oxide in the nose, and to explore the mechanism of its treatment of allergic rhinitis. Method:Twenty patients with moderate to severe persistent allergic rhinitis were enrolled in a randomized, double-blind, self-controlled study. The nasal cavity was lavaged with hydrogen-rich normal saline and normal saline, and the nasal nitric oxide（nNO） value was tested weekly. Result:The test value of nNO was correlated with the diagnosis and curative effect of allergic rhinitis. The difference of nNO test values before and after treatment of the two lavage fluids was statistically significant（P<0.01）. Conclusion:Hydrogen-rich saline lavage can cause nNO change in nasal cavity which may be used in the treatment of allergic rhinitis.", "conclusion": "Hydrogen-rich saline lavage can cause nNO change in nasal cavity which may be used in the treatment of allergic rhinitis." }, { "pmid": "33324415", "year": 2020, "title": "Hydrogen in Patients With Corticosteroid-Refractory/Dependent Chronic Graft-Versus-Host-Disease: A Single-Arm, Multicenter, Open-Label, Phase 2 Trial", "title_en": null, "title_de": "Wasserstoff bei Patienten mit kortikosteroid-refraktärer/-abhängiger chronischer Graft-versus-Host-Erkrankung: eine einarmige, multizentrische, offene Phase-2-Studie", "journal": "Frontiers in Immunology", "authors": "Qian et al.", "author_search": "qian qian", "doi": "10.3389/fimmu.2020.598359", "doi_url": "https://doi.org/10.3389/fimmu.2020.598359", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33324415/", "url": "https://h2medicine.org/studies/study-qian-2020-chronic-graft-versus-host-disease-phase-2-trial/", "methods": [ "drinking-hrw" ], "indications": [ "immune-system", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2020 · Qian — Hydrogen in Patients With Corticosteroid-Refractory/Dependent Chronic Graft-Versus-Host-Disease: A Single-Arm, Multicenter, Open-Label, Phase 2 Trial", "summary": "In chronic graft-versus-host disease that no longer responded to cortisone, 75 % of patients on hydrogen water achieved an objective improvement — without notable side effects. In the response group, 4-year survival was 86.6 %, in the non-response group 0 %. (Frontiers in Immunology, 2020, single-arm multicenter phase-2 trial, n = 24.)", "assessment": "One of the clinically most serious H₂ indications in this batch — a life-threatening disease with exhausted treatment options, in which H₂ water showed an objective response rate of 75 %. For us usable as a strong plausibility and educational argument for the immunomodulatory/antioxidant profile of H₂ — but never as a therapy promise, certainly not outside the specialized transplant-medicine context. Limitation, stated honestly: small sample (n = 24), single-arm, open design without a control group (no placebo, no blinding), and the spectacular survival difference 86.6 % vs. 0 % is a comparison of responders vs. non-responders — it does not prove a causal life extension by H₂. The good tolerability is the most robust finding.", "abstract": "Chronic graft-versus-host-disease (cGVHD) is the leading cause of late non-relapse mortality after allogeneic hematopoietic stem cell transplantation(HSCT). There is no standard therapy for patients refractory or dependent to corticosteroid treatment. We hypothesized that hydrogen may exert therapeutic effects on cGVHD patients with few side effects. A prospective open-label phase 2 study of hydrogen was conducted. Patients received hydrogen-rich water 4ml/kg orally three times a day. Responses were graded in the skin, mouth, Gastrointestinal(GI), liver, eyes, lungs and joints and fascia every 3 months. A total of 24 patients (median age 27) were enrolled. Of the 24 patients, 18 (75%; 95% CI, 55.1% to 88%) had an objective response. No significant toxicity was observed. The estimated 4-year overall survival rate was 74.7%(95% CI, 54.9%-94.5%). The survival time was significantly prolonged in the response group. The survival rate at 4 years in the response group is significantly higher than the nonresponse group (86.6% vs 0%; p= 0.000132). Hydrogen showed great efficacy on cGVHD patients and long-term administration of hydrogen was not associated with significant toxic effects. The trial was registered at www.ClinicalTrials.Gov, NCT02918188.", "conclusion": "Hydrogen showed great efficacy on cGVHD patients and long-term administration of hydrogen was not associated with significant toxic effects. The trial was registered at www.ClinicalTrials.Gov, NCT02918188." }, { "pmid": "33380580", "year": 2020, "title": "Two weeks of hydrogen inhalation can significantly reverse adaptive and innate immune system senescence patients with advanced non-small cell lung cancer: a self-controlled study", "title_en": null, "title_de": "Zwei Wochen Wasserstoff-Inhalation können die Alterung des adaptiven und angeborenen Immunsystems bei Patienten mit fortgeschrittenem nicht-kleinzelligem Lungenkrebs deutlich umkehren: eine selbstkontrollierte Studie", "journal": "Medical Gas Research", "authors": "Chen et al.", "author_search": "chen chen", "doi": "10.4103/2045-9912.304221", "doi_url": "https://doi.org/10.4103/2045-9912.304221", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33380580/", "url": "https://h2medicine.org/studies/study-chen-2020-inhalation-immune-senescence-lung-cancer/", "methods": [ "inhalation" ], "indications": [ "cancer", "immune-system", "respiratory" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2020 · Chen — Two weeks of hydrogen inhalation can significantly reverse adaptive and innate immune system senescence in patients with advanced non-small cell lung cancer: a self-controlled study", "summary": "Two weeks of hydrogen inhalation normalized aging-typical changes of the immune system in patients with advanced lung cancer. Exhausted and aged cytotoxic T cells returned to the normal range, and several weakened immune-cell types recovered. (Medical Gas Research, 2020, self-controlled study, n = 20.)", "assessment": "Thematically strong for investigating H₂ inhalation as a supportive measure in the oncological context — but precisely here maximum caution is required, so as not to create a health-claim overreach. The study shows changes of immune-cell markers in the blood, not that patients live longer or that tumors shrink. Notable as a mechanism/plausibility building block (immunomodulatory profile of H₂), never as a therapy promise in cancer. Limitation, stated honestly: small sample (n = 20), no control group (self-control, before-after), surrogate endpoints instead of clinical outcomes, short duration. Tagged in PubMed as a „Randomized Controlled Trial“, but the title and abstract describe a self-controlled design — hence conservatively classified here as pilot/open-label (evidence level 2).", "abstract": "Following standard treatments, the traditional model for enhancing anti-tumor immunity involves performing immune reconstitution (e.g., adoptive immune cell therapies or immunoenhancing drugs) to prevent recurrence. For patients with advanced non-small cell lung cancer, we report here on two objectives, the immunosenescence for advanced non-small cell lung cancer and hydrogen gas inhalation for immune reconstitution. From July 1st to September 25th, 2019, 20 non-small cell lung cancer patients were enrolled to evaluate the immunosenescence of peripheral blood lymphocyte subsets, including T cell, natural killer/natural killer T cell and gamma delta T cell. Two weeks of hydrogen inhalation was performed during the waiting period for treatment-related examination. All patients inhaled a mixture of hydrogen (66.7%) and oxygen (33.3%) with a gas flow rate of 3 L/min for 4 hours each day. None of the patients received any standard treatment during the hydrogen inhalation period. After pretreatment testing, major indexes of immunosenescence were observed. The abnormally higher indexes included exhausted cytotoxic T cells, senescent cytotoxic T cells, and killer Vδ1 cells. After 2 weeks of hydrogen therapy, the number of exhausted and senescent cytotoxic T cells decreased to within the normal range, and there was an increase in killer Vδ1 cells. The abnormally lower indexes included functional helper and cytotoxic T cells, Th1, total natural killer T cells, natural killer, and Vδ2 cells. After 2 weeks of hydrogen therapy, all six cell subsets increased to within the normal range. The current data indicate that the immunosenescence of advanced non-small cell lung cancer involves nearly all lymphocyte subsets, and 2 weeks of hydrogen treatment can significantly improve most of these indexes. The study was approved by the Ethics Committee of Fuda Cancer Hospital, Jinan University in China (approval No. Fuda20181207) on December 7th, 2018, and was registered on ClinicalTrials.gov (ID: NCT03818347) on January 24th, 2019.", "conclusion": "The study was approved by the Ethics Committee of Fuda Cancer Hospital, Jinan University in China (approval No. Fuda20181207) on December 7th, 2018, and was registered on ClinicalTrials.gov (ID: NCT03818347) on January 24th, 2019." }, { "pmid": "33419292", "year": 2020, "title": "Antioxidant Activity of Hydrogen Water Mask Pack Composed of Gel-Type Emulsion and Hydrogen Generation Powder.", "title_en": null, "title_de": "Antioxidative Aktivität einer Wasserstoffwasser-Maskenpackung aus gelartiger Emulsion und wasserstofferzeugendem Pulver", "journal": "International journal of molecular sciences", "authors": "Kwon et al.", "author_search": "kwon kwon", "doi": "10.3390/ijms21249731", "doi_url": "https://doi.org/10.3390/ijms21249731", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33419292/", "url": "https://h2medicine.org/studies/study-kwon-2020-antioxidant-activity-mask-pack/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise", "skin-aging", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2020 · Kwon — Antioxidant Activity of Hydrogen Water Mask Pack Composed of Gel-Type Emulsion and Hydrogen Generation Powder", "summary": "A cosmetic mask pack containing zinc carbonate-derived hydrogen-generating powder was tested in vitro for antioxidant activity and in a small clinical pilot for skin density effects. After 4 weeks, participants using the hydrogen mask pack showed an 18.4 % increase in skin density versus 9.9 % in the control group. This is an in-vitro and preliminary clinical pilot study — not a controlled clinical trial. (International Journal of Molecular Sciences, 2020.)", "assessment": "This is an in-vitro and small pilot study, not a controlled clinical trial. The antioxidant measurements are standard and credible at the bench level, but the clinical component lacks detail on sample size, blinding, and randomisation. The skin density result is intriguing but cannot be considered robust evidence. This study does not provide proof that hydrogen mask packs meaningfully improve skin aging in humans. It is best read as a proof-of-concept showing that a hydrogen-generating powder can be formulated into a cosmetic matrix and releases detectable H₂ — the clinical relevance remains to be established in properly powered trials.", "abstract": "In this study, hydrogen generation powder samples were prepared using zinc carbonate as a precursor, at a temperature varying from 400 to 700 °C in H2 atmosphere, and were characterized in terms of antioxidant activity. The concentration of dissolved hydrogen obtained by the powder samples was measured using a dissolved hydrogen meter as a function of time. In addition, the antioxidant activity of the samples was evaluated based on the Oyaizu's method, removal rate of ·OH radicals, and ferric reducing antioxidant power. Finally, the hydrogen mask pack was fabricated using the hydrogen generation powder sample and gel-type emulsion. In the clinical test on the mask pack, the effect of the mask on skin aging was characterized and compared to that of a commercial sample. The skin densities of the participants in the experimental group and the control group increased by 18.41% and 9.93% after 4 weeks, respectively. The improved skin density of the participants who used the hydrogen mask pack in the experimental group, might be attributed to the recovery effect of the hydrogen molecule in the mask pack on the denatured thick skin layer.", "conclusion": "The skin densities of the participants in the experimental group and the control group increased by 18.41% and 9.93% after 4 weeks, respectively. The improved skin density of the participants who used the hydrogen mask pack in the experimental group, might be attributed to the recovery effect of the hydrogen molecule in the mask pack on the denatured thick skin layer." }, { "pmid": "33004708", "year": 2020, "title": "Effects of hydrogen-rich water prepared by alternating-current-electrolysis on antioxidant activity, DNA oxidative injuries, and diabetes-related markers.", "title_en": null, "title_de": "Wirkungen von wasserstoffreichem Wasser, hergestellt durch Wechselstrom-Elektrolyse, auf die antioxidative Aktivität, DNA-oxidative Schäden und diabetesbezogene Marker.", "journal": "Medical gas research", "authors": "Asada et al.", "author_search": "asada asada", "doi": "10.4103/2045-9912.296041", "doi_url": "https://doi.org/10.4103/2045-9912.296041", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33004708/", "url": "https://h2medicine.org/studies/study-asada-2020-prepared-alternating-current-electrolysis/", "methods": [ "drinking-hrw" ], "indications": [ "diabetes", "skin-aging", "oxidative-stress", "fundamentals-safety" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2020 · Asada et al. — Effects of hydrogen-rich water prepared by alternating-current-electrolysis on antioxidant activity, DNA oxidative injuries, and diabetes-related markers.", "summary": "Hydrogen-rich water produced by alternating-current (AC) electrolysis — reaching nearly the theoretical maximum H₂ concentration of 1.55 mg/L — showed promising effects on blood glucose markers and systemic DNA oxidative damage in nine people with elevated diabetes-related serum markers over eight weeks. Notably, the H₂ nanobubbles in this preparation resisted boiling, which thermodynamically contradicts Henry's law and may explain improved stability. (Medical Gas Research, 2020.)", "assessment": "The paper contributes an interesting AC-electrolysis production method that achieves near-saturation H₂ at physiological pH — a meaningful technical advance if confirmed. The clinical arm, however, is very weak: n = 9, no control group, no blinding, and outcomes described only as „significant tendencies“. Limitations: uncontrolled design makes confounding (diet, season, regression to the mean) impossible to rule out; the nanobubble boiling-resistance claim is extraordinary and lacks mechanistic explanation; the abstract is partly replaced by an ethics-approval statement. Overall: promising signal for AC-electrolysis production; insufficient evidence for diabetes claims.", "abstract": "Hydrogen-rich water is conventionally prepared by direct current-electrolysis, but has been not or scarcely prepared by alternating current (AC)-electrolysis. The AC preparations from tap water for 20-30 minutes exhibit a dissolved hydrogen concentration of 1.55 mg/L, which was close to the theoretical maximum value of 1.6 mg/L. These preparations also displayed an oxidation-reduction potential of -270 mV (tap water: +576 mV) and pH of 7.7-7.8, being closer to physiological values of body fluids than general types of direct current-electrolytic hydrogen-rich water. We examined whether AC-electrolytic hydrogen-water is retained for hydrogen-abundance after boiling or for antioxidant abilities, and whether the oral administration of this water is clinically effective for diabetes and prevention against systemic DNA-oxidative injuries. 5,5-Dimethyl-1-pyrroline-N-oxide spin trapping and electron spin resonance revealed that the hydrogen-rich water generated by AC-electrolysis exhibited hydroxyl-radical-scavenging activities. Laser nanoparticle tracking method revealed that nanoparticle suspensions as abundant as 5.4 × 107/mL were efficiently retained (up to 3.5 × 107/mL) even after boiling for 10 minutes, being thermodynamically contrary to Henry's law. Oral intake of hydrogen-rich water, 1500 mL per day, lasted for 8 weeks in nine people with the diabetes-related serum markers beyond the normal ranges. The subjects exhibited significant tendencies for the decreased fasting blood glucose and fructosamine, and for the increased 1,5-anhydro-D-glucitol, concomitantly with significant decreases in urinary 8-hydroxy-2-deoxyguanosine contents and its rate of generation. Hydrogen-rich water prepared by AC-electrolysis may be effective in improving diverse diabetes-related markers and systemic DNA oxidative injuries through the formation of abundant heat-resistant nanobubbles and the increased hydrogen concentrations. The study protocol was officially approved by the Medical Ethics Committee of the Japanese Center for Anti-Aging Medical Sciences (approval No. 01S02) on September 15, 2009.", "conclusion": "The study protocol was officially approved by the Medical Ethics Committee of the Japanese Center for Anti-Aging Medical Sciences (approval No. 01S02) on September 15, 2009." }, { "pmid": "33004705", "year": 2020, "title": "Inhalation of molecular hydrogen increases breath acetone excretion during submaximal exercise: a randomized, single-blinded, placebo-controlled study.", "title_en": null, "title_de": "Inhalation von molekularem Wasserstoff erhöht die Aceton-Ausscheidung in der Atemluft bei submaximaler Belastung: eine randomisierte, einfachblinde, placebokontrollierte Studie.", "journal": "Medical gas research", "authors": "Hori et al.", "author_search": "hori hori", "doi": "10.4103/2045-9912.296038", "doi_url": "https://doi.org/10.4103/2045-9912.296038", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/33004705/", "url": "https://h2medicine.org/studies/study-hori-2020-inhalation-increases-breath-acetone/", "methods": [ "inhalation" ], "indications": [ "metabolic", "liver", "sports-exercise", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2020 · Hori et al. — Inhalation of molecular hydrogen increases breath acetone excretion during submaximal exercise: a randomized, single-blinded, placebo-controlled study.", "summary": "Inhaling 1 % H₂ gas during moderate-intensity cycling significantly increased breath acetone levels and oxygen uptake in ten healthy men — suggesting that H₂ promotes hepatic lipid metabolism during aerobic exercise. At rest, however, H₂ inhalation had no effect on these parameters, and oxidative stress markers were unchanged throughout. (Medical Gas Research, 2020.)", "assessment": "The study is a well-designed small pilot with a clear hypothesis and an interesting positive result. Breath acetone as a lipid-metabolism proxy is methodologically sound. The limitations are significant: single-blinded (participants knew whether they received H₂), very small sample, and no direct measurement of fat oxidation or hepatic markers. The null result for oxidative stress is honest and reported transparently. The exercise-specific effect (no resting effect) is biologically plausible but requires replication in larger, double-blinded trials before clinical conclusions can be drawn.", "abstract": "Aerobic exercise is widely accepted as a beneficial option for reducing fat in humans. Recently, it has been suggested that molecular hydrogen (H2) augments mitochondrial oxidative phosphorylation. Therefore, the hypothesis that inhaling H2 could facilitate lipid metabolism during aerobic exercise was investigated in the current study by measuring the breath acetone levels, which could be used as non-invasive indicators of lipid metabolism. This study aimed to investigate the effect of inhaling H2 on breath acetone output during submaximal exercise using a randomized, single-blinded, placebo-controlled, and cross-over experimental design. After taking a 20-minute baseline measurement, breath acetone levels were measured in ten male subjects who performed a 60% peak oxygen uptake-intensity cycling exercise for 20 minutes while inhaling either 1% H2 or a control gas. In another experiment, six male subjects remained in a sitting position for 45 minutes while inhaling either 1% H2 or a control gas. H2 significantly augmented breath acetone and enhanced oxygen uptake during exercise (P < 0.01). However, it did not significantly change oxidative stress or antioxidant activity responses to exercise, nor did it significantly alter the breath acetone or oxygen uptake during prolonged resting states. These results suggest that inhaling H2 gas promotes an exercise-induced increase in hepatic lipid metabolism. The study was approved by the Ethical Committee of Chubu University, Japan (approved No. 260086-2) on March 29, 2018.", "conclusion": "The study was approved by the Ethical Committee of Chubu University, Japan (approved No. 260086-2) on March 29, 2018." }, { "pmid": "32865158", "year": 2020, "title": "COVID-19 and molecular hydrogen inhalation.", "title_en": null, "title_de": "COVID-19 und Inhalation von molekularem Wasserstoff", "journal": "Therapeutic advances in respiratory disease", "authors": "Ostojic", "author_search": "ostojic ostojic", "doi": "10.1177/1753466620951051", "doi_url": "https://doi.org/10.1177/1753466620951051", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32865158/", "url": "https://h2medicine.org/studies/study-ostojic-2020-covid-inhalation/", "methods": [ "inhalation" ], "indications": [ "respiratory" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2020 · Ostojic — COVID-19 and Molecular Hydrogen Inhalation", "summary": "This is a brief theoretical commentary exploring whether molecular hydrogen inhalation could play a supportive role in COVID-19 management, based on H₂'s known anti-inflammatory and antioxidant properties. No abstract text was available for this publication; the entry is based solely on the article's metadata and title. No clinical or experimental data are cited here. (Therapeutic Advances in Respiratory Disease, 2020.)", "assessment": "This is a theoretical commentary with no available abstract. Its subject classification as „theory“ and evidence level (ev=1) reflect that it presents a hypothesis or early conceptual discussion rather than experimental or clinical data. No conclusions about H₂ efficacy in COVID-19 can be drawn from this entry. The original article should be consulted for its full argument. This type of commentary is common early in emerging situations and is best treated as a hypothesis-generating document, not as evidence of therapeutic benefit.", "abstract": null, "conclusion": null }, { "pmid": "32739699", "year": 2020, "title": "Bio-electrochemical COD removal for energy-efficient, maximum and robust nitrogen recovery from urine through membrane aerated nitrification.", "title_en": null, "title_de": "Bioelektrochemische CSB-Entfernung für eine energieeffiziente, maximale und robuste Stickstoffrückgewinnung aus Urin durch membranbelüftete Nitrifikation", "journal": "Water research", "authors": "De Paepe et al.", "author_search": "de paepe de paepe", "doi": "10.1016/j.watres.2020.116223", "doi_url": "https://doi.org/10.1016/j.watres.2020.116223", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32739699/", "url": "https://h2medicine.org/studies/study-depaepe-2020-bio-electrochemical-cod-removal/", "methods": [ "inhalation" ], "indications": [ "sports-exercise" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2020 · De Paepe — Bio-electrochemical COD Removal for Energy-efficient, Maximum and Robust Nitrogen Recovery from Urine through Membrane Aerated Nitrification", "summary": "This study develops a two-stage electrochemical urine treatment system for sustainable nitrogen recovery — primarily for space exploration applications. In the first stage, a microbial electrolysis cell removes up to 85 % of organic matter and produces hydrogen gas as a byproduct, while the second stage converts ammoniacal nitrogen to nitrate. This research is focused on wastewater engineering and bioelectrochemistry, not on therapeutic hydrogen. (Water Research, 2020.)", "assessment": "This is an in-vitro / reactor engineering study with no relevance to therapeutic hydrogen in humans. H₂ production is a side-effect of the electrochemical process, not the study focus. The research is solidly conducted and addresses a genuine engineering challenge in closed-loop life support. It provides no evidence for any health benefit of molecular hydrogen. Its inclusion in an H₂-medicine database is marginal — the link is the incidental H₂ production in the MEC step.", "abstract": "Resource recovery from source-separated urine can shorten nutrient cycles on Earth and is essential in regenerative life support systems for deep-space exploration. In this study, a robust two-stage, energy-efficient, gravity-independent urine treatment system was developed to transform fresh real human urine into a stable nutrient solution. In the first stage, up to 85% of the COD was removed in a microbial electrolysis cell (MEC), converting part of the energy in organic compounds (27-46%) into hydrogen gas and enabling full nitrogen recovery by preventing nitrogen losses through denitrification in the second stage. Besides COD removal, all urea was hydrolysed in the MEC, resulting in a stream rich in ammoniacal nitrogen and alkalinity, and low in COD. This stream was fed into a membrane-aerated biofilm reactor (MABR) in order to convert the volatile and toxic ammoniacal nitrogen to non-volatile nitrate by nitrification. Bio-electrochemical pre-treatment allowed to recover all nitrogen as nitrate in the MABR at a bulk-phase dissolved oxygen level below 0.1 mg O2 L-1. In contrast, feeding the MABR directly with raw urine (omitting the first stage), at the same nitrogen loading rate, resulted in nitrogen loss (18%) due to denitrification. The MEC and MABR were characterised by very distinct and diverse microbial communities. While (strictly) anaerobic genera, such as Geobacter (electroactive bacteria), Thiopseudomonas, a Lentimicrobiaceae member, Alcaligenes and Proteiniphilum prevailed in the MEC, the MABR was dominated by aerobic genera, including Nitrosomonas (a known ammonium oxidiser), Moheibacter and Gordonia. The two-stage approach yielded a stable nitrate-rich, COD-low nutrient solution, suitable for plant and microalgae cultivation.", "conclusion": "While (strictly) anaerobic genera, such as Geobacter (electroactive bacteria), Thiopseudomonas, a Lentimicrobiaceae member, Alcaligenes and Proteiniphilum prevailed in the MEC, the MABR was dominated by aerobic genera, including Nitrosomonas (a known ammonium oxidiser), Moheibacter and Gordonia. The two-stage approach yielded a stable nitrate-rich, COD-low nutrient solution, suitable for plant and" }, { "pmid": "32710259", "year": 2020, "title": "Hydrogen-bubbled platinum-colloid suppresses human esophagus- or tongue-carcinoma cells with intracellular platinum-uptake and the diminished normal-cell mortality.", "title_en": null, "title_de": "Wasserstoffbegastes Platin-Kolloid unterdrückt menschliche Speiseröhren- oder Zungenkarzinomzellen bei intrazellulärer Platin-Aufnahme und verminderter Sterblichkeit normaler Zellen", "journal": "Human cell", "authors": "Kato et al.", "author_search": "kato kato", "doi": "10.1007/s13577-020-00402-1", "doi_url": "https://doi.org/10.1007/s13577-020-00402-1", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32710259/", "url": "https://h2medicine.org/studies/study-kato-2020-bubbled-platinum-colloid-suppresses/", "methods": [ "unspecified" ], "indications": [ "cancer" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2020 · Kato — Hydrogen-bubbled Platinum-colloid Suppresses Human Esophagus- or Tongue-carcinoma Cells with Intracellular Platinum-uptake and the Diminished Normal-cell Mortality", "summary": "In cell culture experiments, a combination of hydrogen nano-bubbles and platinum-polyvinylpyrrolidone colloid (PVP-Pt) more strongly suppressed the growth of human esophageal and tongue cancer cells than either agent alone — while showing comparatively less harm to non-malignant epithelial cells. This is an in-vitro study only; no animal or human data are presented. (Human Cell, 2020.)", "assessment": "This is an in-vitro cell culture study — it does not constitute evidence of efficacy in humans or animals. The synergistic anti-tumour effect of H₂ nano-bubbles plus PVP-Pt is an interesting cell-biology finding, but the jump to „applicable for cancer therapy“ in the conclusion is a substantial extrapolation. No conclusions about therapeutic benefit in human cancer patients can be drawn. Further steps would require animal models, toxicology studies, and ultimately clinical trials. The requirement for simultaneous co-administration also adds complexity to any potential clinical translation.", "abstract": "Carcinostatic effects of combined use of hydrogen nano-bubbles (nano-H) and platinum-povidone (PVP--Pt) were examined. Hydrogen-dissolved medium was prepared by hydrogen-gas bubbling with a microporous gas-emittance-terminal into a medium in the absence or presence of PVP-Pt (nano-H, nano-H/PVP-Pt). Human esophagus-derived carcinoma cells KYSE70 were repressed for cell proliferation with nano-H/PVP-Pt more markedly than with nano-H, indicating the hydrogen-intensification for PVP-Pt-alone-carcinostasis. However, the intensified carcinostasis required co-administration of nano-H and PVP-Pt, and no intensified carcinostasis was shown in two-step separate administration of nano-H and PVP-Pt. Furthermore, hydrogen bubbling into PVP-Pt-containing medium achieved more appreciable carcinostasis than mere addition of PVP-Pt into nano-H-containing medium, indicating the potent interaction of hydrogen and PVP-Pt. The nano-H/PVP-Pt-administered human tongue-derived carcinoma cells HSC-4 were repressed for cell proliferation more markedly than pre-malignant human tongue-derived epitheliocytes DOK, concurrently with more abundant intracellular Pt-intake into HSC-4 cells than DOK as analyzed by ICP-MS. Thus, PVP-Pt is able to adsorb hydrogen nano-bubbles on Pt and applicable for cancer therapy by diminishing the side-effects to normal cells.", "conclusion": "The nano-H/PVP-Pt-administered human tongue-derived carcinoma cells HSC-4 were repressed for cell proliferation more markedly than pre-malignant human tongue-derived epitheliocytes DOK, concurrently with more abundant intracellular Pt-intake into HSC-4 cells than DOK as analyzed by ICP-MS. Thus, PVP-Pt is able to adsorb hydrogen nano-bubbles on Pt and applicable for cancer therapy by diminishing t" }, { "pmid": "32553919", "year": 2020, "title": "A lean magnesium-zinc-calcium alloy ZX00 used for bone fracture stabilization in a large growing-animal model.", "title_en": null, "title_de": "Eine schlanke Magnesium-Zink-Calcium-Legierung ZX00 zur Stabilisierung von Knochenbrüchen in einem großen, wachsenden Tiermodell", "journal": "Acta biomaterialia", "authors": "Holweg et al.", "author_search": "holweg holweg", "doi": "10.1016/j.actbio.2020.06.013", "doi_url": "https://doi.org/10.1016/j.actbio.2020.06.013", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32553919/", "url": "https://h2medicine.org/studies/study-holweg-2020-lean-magnesium-zinc-calcium/", "methods": [ "unspecified" ], "indications": [ "joints-rheumatology" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2020 · Holweg — A Lean Magnesium-Zinc-Calcium Alloy ZX00 Used for Bone Fracture Stabilization in a Large Growing-Animal Model", "summary": "This animal study evaluated biodegradable magnesium-zinc-calcium (ZX00) screws for bone fracture fixation in growing sheep, finding no significant difference in screw degradation between fractured and non-fractured bones, and — importantly — no negative effect of incidental hydrogen gas formation on fracture healing. This is preclinical veterinary orthopaedic research; the H₂ gas in this study is an unwanted byproduct of implant degradation, not a therapeutic agent. (Acta Biomaterialia, 2020.)", "assessment": "This is an animal study (large growing-sheep model) in the field of biodegradable orthopaedic implants — it is preclinical research and does not involve therapeutic hydrogen administration. The H₂ gas studied here is an incidental byproduct of magnesium degradation, not an intentional therapeutic agent. This paper is not evidence for or against the therapeutic use of molecular hydrogen. It is relevant for the safety assessment of biodegradable magnesium implants. Results from sheep cannot be directly extrapolated to human patients without further clinical investigation.", "abstract": "Over the last decade, demand has increased for developing new, alternative materials in pediatric trauma care to overcome the disadvantages associated with conventional implant materials. Magnesium (Mg)-based alloys seem to adequately fulfill the vision of a homogeneously resorbable, biocompatible, load-bearing and functionally supportive implant. The aim of the present study is to introduce the high-strength, lean alloy Mg‒0.45Zn‒0.45Ca, in wt% (ZX00), and for the first time investigate the clinical applicability of screw osteosynthesis using this alloy that contains no rare-earth elements. The alloy was applied in a growing sheep model with osteotomized bone (simulating a fracture) and compared to a non-osteotomy control group regarding degradation behavior and fracture healing. The alloy exhibits an ultimate tensile strength of 285.7 ± 3.1 MPa, an elongation at fracture of 18.2 ± 2.1%, and a reduced in vitro degradation rate compared to alloys containing higher amounts of Zn. In vivo, no significant difference between the osteotomized bone and the control group was found regarding the change in screw volume over implantation time. Therefore, it can be concluded that the fracture healing process, including its effects on the surrounding area, has no significant influence on degradation behavior. There was also no negative influence from hydrogen-gas formation on fracture healing. Despite the proximal and distal screws showing chronologically different gas release, the osteotomy showed complete consolidation. STATEMENT OF SIGNIFICANCE: Conventional implants involve several disadvantages in pediatric trauma care. Magnesium-based alloys seem to overcome these issues as discussed in the recent literature. This study evaluates the clinical applicability of high-strength lean Mg‒0.45Zn‒0.45Ca (ZX00) screws in a growing-sheep model. Two groups, one including a simulated fracture and one group without fracture, underwent implantation of the alloy and were compared to each other. No significant difference regarding screw volume was observed between the groups. There was no negative influence of hydrogen-gas formation on fracture healing and a complete fracture consolidation was found after 12 weeks for all animals investigated.", "conclusion": "No significant difference regarding screw volume was observed between the groups. There was no negative influence of hydrogen-gas formation on fracture healing and a complete fracture consolidation was found after 12 weeks for all animals investigated." }, { "pmid": "32541132", "year": 2020, "title": "Hydrogen therapy can be used to control tumor progression and alleviate the adverse events of medications in patients with advanced non-small cell lung cancer.", "title_en": null, "title_de": "Die Wasserstofftherapie kann zur Kontrolle des Tumorfortschritts und zur Linderung unerwünschter Wirkungen von Medikamenten bei Patienten mit fortgeschrittenem nicht-kleinzelligem Lungenkarzinom eingesetzt werden.", "journal": "Medical gas research", "authors": "Chen et al.", "author_search": "chen chen", "doi": "10.4103/2045-9912.285560", "doi_url": "https://doi.org/10.4103/2045-9912.285560", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32541132/", "url": "https://h2medicine.org/studies/study-chen-2020-can-used-control-tumor/", "methods": [ "inhalation" ], "indications": [ "cancer", "respiratory" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2020 · Chen et al. — Hydrogen therapy can be used to control tumor progression and alleviate the adverse events of medications in patients with advanced non-small cell lung cancer.", "summary": "In 58 patients with advanced non-small cell lung cancer (NSCLC), daily H₂ inhalation for up to 5 months — alone or combined with chemotherapy, targeted therapy, or immunotherapy — was associated with symptom improvement, reduced drug adverse events, and longer progression-free and overall survival compared to a non-treated control group. This is an exploratory clinical observation without randomisation across the combined arms, and results must be interpreted with caution. (Medical Gas Research, 2020.)", "assessment": "This study is hypothesis-generating, not confirmatory. The partial randomisation (only the H₂-only arm was truly randomised), the uncontrolled combination therapy arms, and the non-standardised oncological backgrounds make cross-arm comparisons unreliable. The safety signal is encouraging: no haematological toxicity and only minor, self-resolving adverse reactions. Limitations: non-random allocation in four of five arms; baseline differences acknowledged (tumour-mutation genes); small numbers in each sub-group; single centre; observational follow-up. The results justify a properly randomised, multi-centre trial — they do not establish efficacy.", "abstract": "Chemotherapy, targeted therapy, and immunotherapy are used against advanced non-small cell lung cancer. A clinically efficacious method for relieving the adverse events associated of such therapies is lacking. Fifty-eight adult patients were enrolled in our trial to relieve pulmonary symptoms or the adverse events of drugs. Twenty patients who refused drug treatment were assigned equally and randomly to a hydrogen (H2)-only group and a control group. According to the results of tumor-gene mutations and drug-sensitivity tests, 10, 18, and 10 patients were enrolled into chemotherapy, targeted therapy, and immunotherapy groups in which these therapies were combined with H2-therapy, respectively. Patients underwent H2 inhalation for 4-5 hours per day for 5 months or stopped when cancer recurrence. Before study initiation, the demographics (except for tumor-mutation genes) and pulmonary symptoms (except for moderate cough) of the five groups showed no significant difference. During the first 5 months of treatment, the prevalence of symptoms of the control group increased gradually, whereas that of the four treatment groups decreased gradually. After 16 months of follow-up, progression-free survival of the control group was lower than that of the H2-only group, and significantly lower than that of H2 + chemotherapy, H2 + targeted therapy, and H2 + immunotherapy groups. In the combined-therapy groups, most drug-associated adverse events decreased gradually or even disappeared. H2 inhalation was first discovered in the clinic that can be used to control tumor progression and alleviate the adverse events of medications for patients with advanced non-small cell lung cancer. This study was approved by the Ethics Committee of Fuda Cancer Hospital of Jinan University on December 7, 2018 (approval No. Fuda20181207), and was registered at ClinicalTrials.gov (Identifier: NCT03818347) on January 28, 2019.", "conclusion": "This study was approved by the Ethics Committee of Fuda Cancer Hospital of Jinan University on December 7, 2018 (approval No. Fuda20181207), and was registered at ClinicalTrials.gov (Identifier: NCT03818347) on January 28, 2019." }, { "pmid": "32505097", "year": 2020, "title": "Interaction of different cell types with magnesium modified by plasma electrolytic oxidation.", "title_en": null, "title_de": "Interaktion verschiedener Zelltypen mit durch plasmaelektrolytische Oxidation modifiziertem Magnesium", "journal": "Colloids and surfaces. B, Biointerfaces", "authors": "Echeverry-Rendon et al.", "author_search": "echeverry-rendon echeverry-rendon", "doi": "10.1016/j.colsurfb.2020.111153", "doi_url": "https://doi.org/10.1016/j.colsurfb.2020.111153", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32505097/", "url": "https://h2medicine.org/studies/study-echeverryrendon-2020-interaction-different-cell-types/", "methods": [ "inhalation" ], "indications": [ "metabolic", "liver", "cardiovascular", "skin-aging", "immune-system" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2020 · Echeverry-Rendon — Interaction of Different Cell Types with Magnesium Modified by Plasma Electrolytic Oxidation", "summary": "This in-vitro study examined how surface coatings applied to biodegradable magnesium via plasma electrolytic oxidation (PEO) affect vascular cells, immune cells, and adipose-derived stromal cells — finding that the coatings support stromal cell adhesion but that vascular cells remain vulnerable to compounds released during Mg degradation. Hydrogen gas appears here as a cytotoxic byproduct of magnesium corrosion, not as a therapeutic agent. (Colloids and Surfaces B: Biointerfaces, 2020.)", "assessment": "This is an in-vitro cell biology study in the field of biodegradable implant materials. H₂ gas is explicitly framed as a cytotoxic byproduct of Mg degradation — this is the opposite of therapeutic hydrogen. The study provides useful cell-biology data for implant material scientists, but has no direct relevance to H₂ supplementation or therapeutic hydrogen medicine. No conclusions about H₂ health benefits can be drawn from this work. Results are in-vitro only and require in-vivo validation.", "abstract": "Magnesium (Mg) is a material widely used in industrial applications due to its low weight, ductility, and excellent mechanical properties. For non-permanent implants, Mg is particularly well-suited because of its biodegradability, while its degradation products are not harmful. However, Mg is chemically reactive, and cytotoxic hydrogen gas is released as part of the degradation. This adverse degradation can be tuned using plasma electrolytic oxidation (PEO). With PEO, a surface layer of MgO/Mg(OH)2 is deposited on the surface of Mg in a controlled way. The electrolytes used during PEO influence the surface's chemistry and topography and thus expectedly the biological response of adhered cells. In this study, thin samples of commercial pure of Mg (c.p Mg) were modified by PEO guided by different electrolytes, and the biological activity was assessed on vascular cells, immune cells, and repair cells (adipose tissue-derived stromal cells, ASCs). Vascular cells were more vulnerable than ASCs for compounds released by surface-coated Mg. All surface coatings supported the proliferation of adhered ASC. Released compounds from surface-coated Mg delayed but did not block in vitro wound closure of fibroblasts monolayers. Preformed endothelial tubes were vulnerable for released compounds, while their supporting ASC was not. We conclude that PEO-based surface-coating of Mg supports adhesion and future delivery of therapeutic vascular repair cells such as ASC, but that the observed vulnerability of vascular cells for coated Mg components warrants investigations in vivo.", "conclusion": "Preformed endothelial tubes were vulnerable for released compounds, while their supporting ASC was not. We conclude that PEO-based surface-coating of Mg supports adhesion and future delivery of therapeutic vascular repair cells such as ASC, but that the observed vulnerability of vascular cells for coated Mg components warrants investigations in vivo." }, { "pmid": "32479062", "year": 2020, "title": "Photoactivated H2 Nanogenerator for Enhanced Chemotherapy of Bladder Cancer.", "title_en": null, "title_de": "Photoaktivierter H₂-Nanogenerator für eine verbesserte Chemotherapie des Blasenkarzinoms", "journal": "ACS nano", "authors": "Sun et al.", "author_search": "sun sun", "doi": "10.1021/acsnano.0c01300", "doi_url": "https://doi.org/10.1021/acsnano.0c01300", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32479062/", "url": "https://h2medicine.org/studies/study-sun-2020-photoactivated-nanogenerator-enhanced-chemotherapy/", "methods": [ "inhalation" ], "indications": [ "sports-exercise", "cancer", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2020 · Sun — Photoactivated H₂ Nanogenerator for Enhanced Chemotherapy of Bladder Cancer", "summary": "Researchers designed nanoparticles that generate H₂ gas inside cancer cells when activated by a 660 nm laser, finding in cell culture and mouse models that H₂ produced in this way significantly enhanced the efficacy of the chemotherapy drug gemcitabine against bladder cancer. The mechanism involves H₂-induced inhibition of mitochondrial function and reduction of a drug-efflux pump, making cancer cells less able to expel the chemotherapy drug. This is an in-vitro and animal study — not a human clinical trial. (ACS Nano, 2020.)", "assessment": "This is an in-vitro and animal study — specifically a mouse xenograft model — in the field of nano-oncology. The concept is scientifically creative, but all results are preclinical. No conclusions about efficacy or safety in human bladder cancer patients can be drawn. The delivery system (intravesical laser irradiation of nanoparticles) involves significant engineering complexity and safety questions that would require extensive preclinical and clinical development before any human application. The H₂ here acts as a chemotherapy sensitiser via a specific engineered nanoparticle mechanism — not as a standalone therapeutic.", "abstract": "Hydrogen gas can mitigate oxidative stress in many diseases and is regarded to be safe and free of side effects. Inspired by a metalloenzyme in a variety of microorganisms, here, we propose a photoactivated H2 nanogenerator that comprises a fluorinated chitosan (FCS), a chemotherapeutic drug (gemcitabine, GEM), and a catalyst of H2 production ([FeFe]TPP) that can form self-assembled [FeFe]TPP/GEM/FCS nanoparticles (NPs). The [FeFe]TPP/GEM/FCS NPs exhibit excellent transmucosal and tumor cell penetration capacities after intravesical instillation into the bladder and can efficiently produce H2 gas in situ upon 660 nm laser irradiation, which significantly enhances the efficacy of hydrogen chemotherapy of cancer in vitro and in vivo. Moreover, we discover that H2 gas in hydrogen chemotherapy can inhibit mitochondrial function, hinder ATP synthesis, and cause a reduction of the P-gp efflux pump function, which finally attenuates P-gp protein drug transport capacity in cancer cells. This photoactivated H2 evolution in situ to improve the therapeutic efficacy of chemotherapy of bladder cancer may present an effective hydrogen chemotherapy strategy for cancer treatment.", "conclusion": "Moreover, we discover that H2 gas in hydrogen chemotherapy can inhibit mitochondrial function, hinder ATP synthesis, and cause a reduction of the P-gp efflux pump function, which finally attenuates P-gp protein drug transport capacity in cancer cells. This photoactivated H2 evolution in situ to improve the therapeutic efficacy of chemotherapy of bladder cancer may present an effective hydrogen che" }, { "pmid": "32407476", "year": 2020, "title": "Hydrogen gas (XEN) inhalation ameliorates airway inflammation in asthma and COPD patients.", "title_en": null, "title_de": "Inhalation von Wasserstoffgas (XEN) verbessert die Atemwegsentzündung bei Asthma- und COPD-Patienten.", "journal": "QJM : monthly journal of the Association of Physicians", "authors": "Wang et al.", "author_search": "wang wang", "doi": "10.1093/qjmed/hcaa164", "doi_url": "https://doi.org/10.1093/qjmed/hcaa164", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32407476/", "url": "https://h2medicine.org/studies/study-wang-2020-xen-inhalation-ameliorates-airway/", "methods": [ "inhalation" ], "indications": [ "cancer", "respiratory", "immune-system", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2020 · Wang et al. — Hydrogen gas (XEN) inhalation ameliorates airway inflammation in asthma and COPD patients.", "summary": "A single 45-minute inhalation of hydrogen-containing steam (2.4 % H₂) reduced key inflammatory cytokines in airways of 10 asthma and 10 COPD patients — including monocyte chemotactic protein 1 in both groups and IL-8 in asthma. The acute reduction in airway inflammation markers is encouraging, though the study examines only a one-time intervention and does not assess clinical symptoms or lung function. (QJM, 2020.)", "assessment": "Proof-of-concept data for acute anti-inflammatory effects of H₂ inhalation in obstructive airway disease. The MCP-1 reduction across both conditions is the most robust signal. Limitations: very small sample (10 per group); no sham control; single session — no sustainability data; no lung function (FEV₁, FVC) or symptom endpoints; the increase in EBC soluble CD40L in COPD after H₂ is unexplained and could indicate a complex immune interaction. Results warrant a multi-session, controlled trial with clinical endpoints.", "abstract": "BACKGROUND: Hydrogen was proven to have anti-oxidative and anti-inflammation effects to various diseases. AIM: We wish to investigate the acute effects of inhaled hydrogen on airway inflammation in patients with asthma and chronic obstructive pulmonary disease (COPD). DESIGN: Prospective study. METHODS: In total, 2.4% hydrogen containing steam mixed gas (XEN) was inhaled once for 45 min in 10 patients with asthma and 10 patients with COPD. The levels of granulocyte-macrophage colony stimulating factor, interferon-γ, interleukin-1β (IL-1β), IL-2, IL-4, IL-6 and so on in peripheral blood and exhaled breath condensate (EBC) before and after 'XEN' inhalation were measured. RESULTS: 45 minutes 'XEN' inhalation once decreased monocyte chemotactic protein 1 level in both COPD (564.70-451.51 pg/mL, P = 0.019) and asthma (386.39-332.76 pg/mL, P = 0.033) group, while decreased IL-8 level only in asthma group (5.25-4.49 pg/mL, P = 0.023). The level of EBC soluble cluster of differentiation-40 ligand in COPD group increased after inhalation (1.07-1.16 pg/mL, P = 0.031), while IL-4 and IL-6 levels in EBC were significantly lower after inhalation in the COPD (0.80-0.64 pg/mL, P = 0.025) and asthma (0.06-0.05 pg/mL, P = 0.007) group, respectively. CONCLUSIONS: A single inhalation of hydrogen for 45 min attenuated inflammatory status in airways in patients with asthma and COPD.", "conclusion": "A single inhalation of hydrogen for 45 min attenuated inflammatory status in airways in patients with asthma and COPD." }, { "pmid": "32399209", "year": 2020, "title": "Case Report: Acute hydrotherapy with super-saturated hydrogen-rich water for ankle sprain in a professional athlete.", "title_en": null, "title_de": "Fallbericht: Akute Hydrotherapie mit übersättigtem wasserstoffreichem Wasser bei einer Knöchelverstauchung eines professionellen Athleten.", "journal": "F1000Research", "authors": "Javorac et al.", "author_search": "javorac javorac", "doi": "10.12688/f1000research.22850.1", "doi_url": "https://doi.org/10.12688/f1000research.22850.1", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32399209/", "url": "https://h2medicine.org/studies/study-javorac-2020-acute-hydrotherapy-super-saturated/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise", "immune-system" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2020 · Javorac et al. — Case Report: Acute hydrotherapy with super-saturated hydrogen-rich water for ankle sprain in a professional athlete.", "summary": "A professional athlete with a grade II ankle sprain received six sessions of 30-minute H₂-rich water hydrotherapy within the first 24 hours post-injury, with notable improvements in pain (VAS 50 → 20), ankle swelling (–2.8 %), and dorsiflexion range of motion (+27.9 %) by the 24-hour follow-up. This is a single-patient case report — it shows feasibility and generates hypotheses but cannot establish effectiveness. (F1000Research, 2020.)", "assessment": "A single case report — useful as a hypothesis generator and for documenting feasibility and safety of the intervention, but carrying essentially no inferential weight regarding effectiveness. The comparison to the RICE protocol is asserted rather than tested. Limitations: n = 1; no control; natural recovery within 24 hours confounds all outcome changes; H₂ concentration in the water not specified; outcome assessor (the patient himself for VAS) is not blinded. The authors correctly frame conclusions as „might be helpful“ — this framing is appropriate and should be maintained.", "abstract": "Background: The traditional treatment of soft tissue injuries consists of the RICE protocol - rest, ice, compression, and elevation, followed for up to 72 hours after a trauma. Although designed as an immediate therapy to reduce inflammation that occurs after an acute injury, the RICE protcol might not be the best way to promote healing due to limiting blood flow. Molecular hydrogen (H 2) has recently been put forward as a possible adjuvant treatment in musculoskeletal medicine, yet limited data are available concerning its effectiveness as a first-aid intervention. Case report: We report here a case of an elite professional athlete who suffered a grade II ankle sprain, and who subsequently received six sessions of ankle and foot hydrotherapy (e.g. 30-min at every four hours) with super-saturated hydrogen-rich water during the first 24 hours post-injury. The pain VAS self-completed by the patient dropped from 50 points (moderate pain) at baseline (immediately after injury) to 20 points (mild pain) at 24-h follow-up. Ankle swelling dropped by 2.8% and dorsiflexion range of movement improved by 27.9% from baseline to follow-up, respectively. Conclusions: Our case has indicated that an acute multi-session hydrotherapy with hydrogen-rich water might be a helpful treatment in terms of pain, swelling reduction and regaining range of motion after an ankle sprain.", "conclusion": "Our case has indicated that an acute multi-session hydrotherapy with hydrogen-rich water might be a helpful treatment in terms of pain, swelling reduction and regaining range of motion after an ankle sprain." }, { "pmid": "32380825", "year": 2020, "title": "NIR-Driven Water Splitting H2 Production Nanoplatform for H2-Mediated Cascade-Amplifying Synergetic Cancer Therapy.", "title_en": null, "title_de": "NIR-getriebene Nanoplattform zur H₂-Produktion durch Wasserspaltung für eine H₂-vermittelte, kaskadenverstärkende synergistische Krebstherapie", "journal": "ACS applied materials & interfaces", "authors": "Wang et al.", "author_search": "wang wang", "doi": "10.1021/acsami.0c03852", "doi_url": "https://doi.org/10.1021/acsami.0c03852", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32380825/", "url": "https://h2medicine.org/studies/study-wang-2020-nir-driven-splitting-production/", "methods": [ "unspecified" ], "indications": [ "cancer", "fundamentals-safety" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2020 · Wang — NIR-Driven Water Splitting H₂ Production Nanoplatform for H₂-Mediated Cascade-Amplifying Synergetic Cancer Therapy", "summary": "This in-vitro and animal study presents a complex nanoparticle system that generates H₂ gas inside tumour cells via near-infrared (NIR) laser-driven water splitting, combining hydrogen gas therapy with photodynamic therapy, photothermal therapy, and chemodynamic therapy in a cascade approach against cancer. All results are preclinical; this is highly specialised nano-oncology engineering with no direct relevance to drinking hydrogen water or H₂ inhalation. (ACS Applied Materials & Interfaces, 2020.)", "assessment": "This is an in-vitro and animal (murine) preclinical study in the highly specialised field of nano-oncology. The H₂ here is generated inside tumour cells via engineered nanoparticles and NIR laser — a completely different context from therapeutic H₂ supplementation. No human data exist and no conclusions about H₂ health benefits in general can be drawn from this work. The multi-modal cancer therapy concept is scientifically sophisticated, but clinical translation of complex nanoparticle systems historically faces major hurdles in toxicology, manufacturing, and regulatory approval.", "abstract": "As a newly emerging treatment strategy for many diseases, hydrogen therapy has attracted a lot of attention because of its excellent biosafety. However, the high diffusivity and low solubility of hydrogen make it difficult to accumulate in local lesions. Herein, we develop a H2 self-generation nanoplatform by in situ water splitting driven by near-infrared (NIR) laser. In this work, core-shell nanoparticles (CSNPs) of NaGdF4:Yb,Tm/g-C3N4/Cu3P (UCC) nanocomposites as core encapsulated with zeolitic imidazolate framework-8 (ZIF-8) modified with folic acid as shell are designed and synthesized. Due to the acid-responsive ZIF-8 shell, enhanced permeability and retention (EPR) effect, and folate receptor-mediated endocytosis, CSNPs are selectively captured by tumor cells. Upon 980 nm laser irradiation, CSNPs exhibit a high production capacity of H2 and active oxygen species (ROS), as well as an appropriate photothermal conversion temperature. Furthermore, rising temperature increases the Fenton reaction rate of Cu(I) with H2O2 and strengthens the curative effect of chemodynamic therapy (CDT). The excess glutathione (GSH) in tumor microenvironment (TME) can deplete positive holes produced in the valence band of g-C3N4 in the g-C3N4/Cu3P Z-scheme heterojunction. GSH also can reduce Cu(II) to Cu(I), ensuring a continuous Fenton reaction. Thus, a NIR-driven H2 production nanoplatform is constructed for H2-mediated cascade-amplifying multimodal synergetic therapy.", "conclusion": "GSH also can reduce Cu(II) to Cu(I), ensuring a continuous Fenton reaction. Thus, a NIR-driven H2 production nanoplatform is constructed for H2-mediated cascade-amplifying multimodal synergetic therapy." }, { "pmid": "32376537", "year": 2020, "title": "[Hydrogen water alleviates paraquat-induced lung fibroblast injury in vitro by enhancing Nrf2 expression].", "title_en": null, "title_de": "Wasserstoffwasser lindert Paraquat-induzierte Schäden an Lungenfibroblasten in vitro durch Verstärkung der Nrf2-Expression", "journal": "Nan fang yi ke da xue xue bao = Journal of Southern Medical University", "authors": "Li et al.", "author_search": "li li", "doi": "10.12122/j.issn.1673-4254.2020.02.15", "doi_url": "https://doi.org/10.12122/j.issn.1673-4254.2020.02.15", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32376537/", "url": "https://h2medicine.org/studies/study-li-2020-alleviates-paraquat-induced-lung/", "methods": [ "drinking-hrw" ], "indications": [ "respiratory", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2020 · Li — Hydrogen Water Alleviates Paraquat-induced Lung Fibroblast Injury In Vitro by Enhancing Nrf2 Expression", "summary": "In human lung fibroblasts exposed to the herbicide paraquat, hydrogen-rich water treatment reduced cell damage markers and inhibited fibrosis-related collagen production — an effect that worked through upregulation of the antioxidant transcription factor Nrf2. This is an in-vitro cell culture study; results cannot be transferred directly to human patients. (Journal of Southern Medical University, 2020.)", "assessment": "This is an in-vitro cell culture study — a useful mechanistic investigation, but not evidence of therapeutic efficacy in humans. The Nrf2-mediated antioxidant mechanism is plausible and consistent with other H₂ research, but paraquat poisoning is an extreme toxic model not representative of typical human lung conditions. Additionally, the jump from cell-level Nrf2 upregulation to clinical benefit in pulmonary fibrosis requires substantial further investigation including animal models and human trials. Results should not be interpreted as evidence that hydrogen water treats lung disease in humans.", "abstract": "OBJECTIVE: To investigate the effects of hydrogen water on proliferation, differentiation, collagen secretion and Nrf2 expression in paraquat-induced human lung fibroblasts. METHODS: In vitro cultured human lung fibroblasts (HFL1) exposed to 600 μmol/L paraquat (PQ) for 24 h were treated with hydrogen water with or without RNA interference of Nrf2 expression. The changes in the cell proliferation were examined using MTT assay, and the expressions of Col-I, Col-III, α-SMA and Nrf2 in the cells were detected using Western blotting, real-time quantitative PCR and immunofluorescence assay. The contents of SOD, CAT and GSH in the cells were determined with ELISA. RESULTS: Compared with the PQ-exposed cells, the cells with hydrogen water treatment showed significantly lowered expressions of Col-I, Col-III, and α-SMA. Interference of Nrf2 expression obviously attenuated the effect of hydrogen water on PQ-exposed cells. Hydrogen water treatment significantly increased the expression of Nrf2 and promoted the production of the antioxidants in PQ-exposed lung fibroblasts. CONCLUSIONS: Hydrogen water enhances Nrf2 expression to promote the proliferation and production of antioxidants and inhibit the differentiation and collagen secretion in PQ-exposed human lung fibroblasts in vitro.", "conclusion": "Hydrogen water enhances Nrf2 expression to promote the proliferation and production of antioxidants and inhibit the differentiation and collagen secretion in PQ-exposed human lung fibroblasts in vitro." }, { "pmid": "32314789", "year": 2020, "title": "Hydrogen gas represses the progression of lung cancer via down-regulating CD47.", "title_en": null, "title_de": "Wasserstoffgas unterdrückt den Verlauf von Lungenkrebs durch Herunterregulierung von CD47", "journal": "Bioscience reports", "authors": "Meng et al.", "author_search": "meng meng", "doi": "10.1042/bsr20192761", "doi_url": "https://doi.org/10.1042/bsr20192761", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32314789/", "url": "https://h2medicine.org/studies/study-meng-2020-represses-progression-lung-cancer/", "methods": [ "inhalation" ], "indications": [ "cancer", "respiratory", "skin-aging" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2020 · Meng — Hydrogen Gas Represses the Progression of Lung Cancer via Down-regulating CD47", "summary": "In lung cancer cell lines and a mouse tumour model, hydrogen gas treatment reduced the expression of CD47 — a „don't eat me“ signal that cancer cells use to evade immune destruction — and thereby inhibited cancer cell growth, invasion, migration, and promoted macrophage-mediated tumour cell clearance. This is an in-vitro and animal study; no human data are presented. (Bioscience Reports, 2020.)", "assessment": "This is an in-vitro cell culture and mouse xenograft study — a preclinical investigation only. The CD47-mediated mechanism is scientifically coherent and the confirmation through CD47 gain/loss-of-function experiments is methodologically solid. However, cell line and mouse xenograft results cannot be extrapolated to human lung cancer therapy. CD47 is an active area of cancer immunotherapy research, but the specific role of H₂ in modulating CD47 in human patients is entirely unknown. This study contributes a novel hypothesis — not clinical evidence.", "abstract": "Hydrogen gas (H2) has been identified to play an anti-tumor role in several kinds of cancers, but the molecular mechanisms remain largely unknown. In our previous study, our project group found that H2 could decrease the expression of CD47 in lung cancer A549 cells via the next-generation sequencing, indicating that CD47 might be involved in H2-mediated lung cancer repression. Therefore, the present study aimed to explore the effects of CD47 on H2-induced lung cancer repression. Western blotting and real-time PCR (RT-PCR) assays were used to detect the levels of proteins and mRNAs, respectively. Cell proliferation, invasion, migration and apoptosis were detected by using the cell counting kit-8 (CCK-8), Transwell chambers, wound healing and flow cytometry assays, respectively. The results showed that H2 treatment caused decreases in the expression levels of CD47 and cell division control protein 42 (CDC42) in a dose-dependent manner. Up-regulation of CD47 abolished H2 roles in promoting lung cancer cell apoptosis and repressing cell growth, invasion and migration in both A549 and H1975 cell lines. However, knockdown of CD47 enhanced H2 role in lung cancer inhibition. Moreover, we also observed that H2 treatment induced obvious inhibitions in the expression levels of CDC42 and CD47 in mice tumor tissues, as well as reinforced macrophage-mediated phagocytosis in A549 and H1975 cells. In conclusion, the current study reveals that H2 inhibits the progression of lung cancer via down-regulating CD47, which might be a potent method for lung cancer treatment.", "conclusion": "Moreover, we also observed that H2 treatment induced obvious inhibitions in the expression levels of CDC42 and CD47 in mice tumor tissues, as well as reinforced macrophage-mediated phagocytosis in A549 and H1975 cells. In conclusion, the current study reveals that H2 inhibits the progression of lung cancer via down-regulating CD47, which might be a potent method for lung cancer treatment." }, { "pmid": "32302306", "year": 2020, "title": "Constitutive hydrogen inhalation prevents vascular remodeling via reduction of oxidative stress.", "title_en": null, "title_de": "Kontinuierliche Wasserstoffinhalation verhindert vaskuläres Remodeling durch Reduktion von oxidativem Stress", "journal": "PloS one", "authors": "Kiyoi et al.", "author_search": "kiyoi kiyoi", "doi": "10.1371/journal.pone.0227582", "doi_url": "https://doi.org/10.1371/journal.pone.0227582", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32302306/", "url": "https://h2medicine.org/studies/study-kiyoi-2020-constitutive-inhalation-prevents-vascular/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "cardiovascular", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2020 · Kiyoi — Constitutive Hydrogen Inhalation Prevents Vascular Remodeling via Reduction of Oxidative Stress", "summary": "In a mouse model of cuff-induced vascular injury, continuous inhalation of 1.3 % hydrogen gas for several weeks significantly reduced abnormal vascular wall thickening (neointima formation) — an effect associated with decreased DNA damage and downregulation of the NADPH oxidase NOX1. This is a preclinical animal study; its findings are not directly transferable to human cardiovascular disease. (PLOS ONE, 2020.)", "assessment": "This is an animal study (mouse model) — a preclinical investigation only. The data show a meaningful reduction in neointima formation with H₂ inhalation, with a plausible mechanistic explanation involving selective hydroxyl radical and peroxynitrite reduction. However, mouse cardiovascular models frequently do not translate directly to human disease, and continuous H₂ inhalation as a lifestyle intervention is impractical without substantial further development. The finding is scientifically interesting and supports further investigation, but cannot be used as evidence for cardiovascular benefit of H₂ in humans.", "abstract": "Molecular hydrogen is thought to have an inhibitory effect on oxidative stress, thereby attenuating the onset and progression of various diseases including cardiovascular disease; however, few reports have assessed the preventive effect of constitutive inhalation of hydrogen gas on of vascular remodeling. Here, we investigated the effect of constitutive inhalation of hydrogen gas on vascular neointima formation using a cuff-induced vascular injury mouse model. After constitutive inhalation of compressed hydrogen gas (O2 21%, N2 77.7%, hydrogen 1.3%) or compressed air only (O2 21%, N2 79%) by C57BL/6 mice for 2 weeks from 8 weeks of age in a closed chamber, inflammatory cuff injury was induced by polyethylene cuff placement around the femoral artery under anesthesia, and hydrogen gas administration was continued until sampling of the femoral artery. Neointima formation, accompanied by an increase in cell proliferation, was significantly attenuated in the hydrogen group compared with the control group. NADPH oxidase NOX1 downregulation in response to cuff injury was shown in the hydrogen group, but the expression levels of NADPH oxidase subunits, p40phox and p47phox, did not differ significantly between the hydrogen and control groups. Although the increase in superoxide anion production did not significantly differ between the hydrogen and control groups, DNA damage was decreased as a result of reduction of reactive oxygen species such as hydroxyl radical (⋅OH) and peroxynitrite (ONOO-) in the hydrogen group. These results demonstrate that constitutive inhalation of hydrogen gas attenuates vascular remodeling partly via reduction of oxidative stress, suggesting that constitutive inhalation of hydrogen gas at a safe concentration in the living environment could be an effective strategy for prevention of vascular diseases such as atherosclerosis.", "conclusion": "Although the increase in superoxide anion production did not significantly differ between the hydrogen and control groups, DNA damage was decreased as a result of reduction of reactive oxygen species such as hydroxyl radical (⋅OH) and peroxynitrite (ONOO-) in the hydrogen group. These results demonstrate that constitutive inhalation of hydrogen gas attenuates vascular remodeling partly via reducti" }, { "pmid": "32278311", "year": 2020, "title": "Effect of aggrecan degradation on the nanomechanics of hyaluronan in extra-fibrillar matrix of annulus fibrosus: A molecular dynamics investigation.", "title_en": null, "title_de": "Wirkung des Aggrecan-Abbaus auf die Nanomechanik von Hyaluronan in der extrafibrillären Matrix des Anulus fibrosus: Eine molekulardynamische Untersuchung.", "journal": "Journal of the mechanical behavior of biomedical materials", "authors": "Bhattacharya et al.", "author_search": "bhattacharya bhattacharya", "doi": "10.1016/j.jmbbm.2020.103752", "doi_url": "https://doi.org/10.1016/j.jmbbm.2020.103752", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32278311/", "url": "https://h2medicine.org/studies/study-bhattacharya-2020-aggrecan-degradation-nanomechanics-hyaluronan/", "methods": [ "unspecified" ], "indications": [ "cancer" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2020 · Bhattacharya — Effect of aggrecan degradation on the nanomechanics of hyaluronan in extra-fibrillar matrix of annulus fibrosus: A molecular dynamics investigation.", "summary": "This computational study uses molecular dynamics simulations to examine how hydration — linked to aggrecan degradation — affects the nanoscale mechanical behaviour of hyaluronan in the outer ring of intervertebral discs. Results show that increasing hydration significantly shifts both tensile and compressive stiffness of hyaluronan, helping to explain why water loss in disc degeneration alters spinal mechanics. This is a theoretical in-vitro simulation study with no direct H₂ medicine relevance.", "assessment": "This is a computational biomechanics study, not an H₂ medicine study. It provides mechanistic insight into how water content affects intervertebral disc behaviour at the nanoscale — relevant for spinal degeneration research, not for evaluating therapeutic hydrogen. Limitations: molecular dynamics simulations are model-dependent and cannot substitute for experimental tissue studies or clinical data. No H₂ therapeutic conclusions can be drawn from this paper.", "abstract": "Intervertebral Disc (IVD) Degeneration is one of the primary causes of low back pain among the adult population - the most significant cause being the degradation of aggrecan present in the extra-fibrillar matrix (EFM). Aggrecan degradation is closely associated with loss of water content leading to an alteration in the mechanical behaviour of the IVD. The loss in water content has a significant impact on the chemo-mechanical interplay of IVD biochemical constituents at the fundamental level. This work presents a mechanistic understanding of the effect of hydration, closely associated with aggrecan degradation, on the nanoscale mechanical behaviour of the hyaluronan present in the EFM of the Annulus Fibrosus. For this purpose, explicit three-dimensional molecular dynamics analyses of tensile and compressive tests are performed on a representative atomistic model of the hyaluronan present in the EFM. To account for the degradation of aggrecan, hydration levels are varied from 0 to 75% by weight of water. Analyses show that an increase in the hydration levels decreases the elastic modulus of hyaluronan in tension from ~4.6 GPa to ~2.1 GPa. On the other hand, the increase in hydration level increases the elastic moduli in axial compression from ~1.6 GPa in un-hydrated condition to ~6 GPa in 50% hydrated condition. But as the hydration levels increase to 75%, the elastic modulus reduces to ~3.5 GPa signifying a shift in load-bearing characteristic, from the solid hyaluronan component to the fluid component. Furthermore, analyses show a reduction in the intermolecular energy between hyaluronan and water, under axial tensile loading, indicating a nanoscale intermolecular debonding between hyaluronan and water molecules. This is attributed to the ability of hyaluronan to form stabilizing intra-molecular hydrogen bonds between adjacent residues. Compressive loading, on the other hand, causes intensive coiling of hyaluronan molecule, which traps more water through hydrogen bonding and aids in bearing compressive loads. Overall, study shows that hydration level has a strong influence on the atomistic level interactions between hyaluronan molecules and hyaluronan and water molecules in the EFM which influences the nanoscale mechanics of the Annulus Fibrosus.", "conclusion": "Compressive loading, on the other hand, causes intensive coiling of hyaluronan molecule, which traps more water through hydrogen bonding and aids in bearing compressive loads. Overall, study shows that hydration level has a strong influence on the atomistic level interactions between hyaluronan molecules and hyaluronan and water molecules in the EFM which influences the nanoscale mechanics of the " }, { "pmid": "32236175", "year": 2020, "title": "Effect of thermal treatments on in vitro starch digestibility of sorghum dried noodles.", "title_en": null, "title_de": "Wirkung thermischer Behandlungen auf die In-vitro-Stärkeverdaulichkeit von getrockneten Sorghum-Nudeln.", "journal": "Food & function", "authors": "Liu et al.", "author_search": "liu liu", "doi": "10.1039/c9fo02765c", "doi_url": "https://doi.org/10.1039/c9fo02765c", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32236175/", "url": "https://h2medicine.org/studies/study-liu-2020-thermal-treatments-vitro-starch/", "methods": [ "unspecified" ], "indications": [ "diabetes" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2020 · Liu — Effect of thermal treatments on in vitro starch digestibility of sorghum dried noodles.", "summary": "This food science study investigates how roasting, microwave treatment, stir-frying, and heat-moisture treatment (HMT) of sorghum grains affect the starch digestibility and glycemic index of dried sorghum noodles. HMT-treated noodles showed the highest resistant starch content and the lowest estimated glycemic index. This study does not investigate molecular hydrogen (H₂) as a therapeutic agent.", "assessment": "This is a food science / in-vitro starch digestion study, not an H₂ medicine study. It provides useful data on how thermal processing of sorghum can lower the glycemic index of noodles — relevant to nutritional research for diabetes prevention. No H₂ therapeutic conclusions can be drawn. The mention of „hydrogen bonds“ in FTIR analysis refers to structural chemistry of polysaccharides, entirely distinct from molecular hydrogen (H₂) as a medical gas.", "abstract": "In this paper, sorghum grains were pretreated by roasting (RT), microwave (MW), stir-frying (SF) and heat-moisture treatment (HMT). The effects of pretreated sorghum grains on in vitro starch digestibility of sorghum dried noodles made from sorghum and wheat flour were investigated. The results showed that HMT treated noodles contained the highest amount of resistant starch (RS) and the lowest amount of rapidly digestible starch (RDS). The hydrolysis kinetic parameters and estimated glycemic index (eGI) decreased in all of the treated samples. The treated starches had lower molecular weight and less proportion of short chains of amylopectin than those of the untreated sample. X-ray diffraction demonstrated that the relative crystallinity of starch in noodles was increased by HMT and RT treatments while it was decreased by MW and SF treatments compared to untreated noodles. Fourier transform infrared (FTIR) analysis revealed that the short-range ordered degree and intra-molecular hydrogen bond intensity were both enhanced by thermal treatments. A tighter and smoother microstructure with fewer pores and cracks in the treated noodles was observed by scanning electron microscopy (SEM). These structural changes could provide a better understanding of the lower starch digestion rate.", "conclusion": "A tighter and smoother microstructure with fewer pores and cracks in the treated noodles was observed by scanning electron microscopy (SEM). These structural changes could provide a better understanding of the lower starch digestion rate." }, { "pmid": "32189665", "year": 2020, "title": "Hydrogen-rich water suppresses the reduction in blood total antioxidant capacity induced by 3 consecutive days of severe exercise in physically active males.", "title_en": null, "title_de": "Wasserstoffreiches Wasser unterdrückt die durch 3 aufeinanderfolgende Tage schwerer körperlicher Belastung induzierte Senkung der gesamten antioxidativen Kapazität des Blutes bei körperlich aktiven Männern.", "journal": "Medical gas research", "authors": "Dobashi et al.", "author_search": "dobashi dobashi", "doi": "10.4103/2045-9912.279979", "doi_url": "https://doi.org/10.4103/2045-9912.279979", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32189665/", "url": "https://h2medicine.org/studies/study-dobashi-2020-suppresses-reduction-blood-total/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise", "immune-system", "oxidative-stress" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2020 · Dobashi et al. — Hydrogen-rich water suppresses the reduction in blood total antioxidant capacity induced by 3 consecutive days of severe exercise in physically active males.", "summary": "In a crossover trial with 8 active men, drinking H₂-rich water (5.14 ppm) before and after each of 3 consecutive intense exercise sessions maintained the blood antioxidant status — measured as the BAP/d-ROM ratio — while placebo water allowed it to decline progressively. Exercise performance was not significantly different between conditions, meaning H₂ supported redox balance without masking fatigue or altering output. (Medical Gas Research, 2020.)", "assessment": "A well-structured small crossover trial with a clear readout (redox status) and an honest null finding for performance. The preservation of antioxidant status under repeated exercise stress is a meaningful signal, though the clinical relevance of BAP/d-ROM maintenance in healthy athletes is uncertain. Limitations: n = 8; single-blind; H₂ concentration high (5.14 ppm) — not typical of commercially available products; no long-term follow-up; no muscle biopsy or inflammatory marker data; performance null result is important but was measured 16 hours after exercise (acute performance impact not excluded).", "abstract": "Repeated sprint exercise can interfere with intramuscular redox balance and cause systemic oxidative stress and muscle damage. There is growing evidence that molecular hydrogen counteracts oxidative and/or inflammatory responses. Therefore, we investigated the effects of molecular hydrogen-rich water (HW) on muscle performance and oxidative stress markers induced by strenuous exercise. A single-blind, crossover, randomized controlled trial has been designed. Eight male volunteers completed two 3-day consecutive exercise tests under two conditions: HW and placebo water (PW). The exercise test included a countermovement jump, maximal voluntary isometric contraction of knee extensors, and sprint cycling. The sprint cycling exercise was comprised three repetitions of 10-second maximal pedaling against a resistance of 7.5% body mass and 110-second active rest (no-load pedaling). Before and after the exercise test, participants drank the 500 mL of HW (5.14 ± 0.03 ppm in H2 concentration) or PW (0.00 ± 0.00 ppm). At 7 hours before the first exercise test (Day 1), as baseline, and 16 hours after the exercise test on each day, blood samples were obtained. Exercise performances in both conditions were not significantly different over 3 consecutive days. In PW trial, relative changes in biological antioxidant potential/diacron-reactive oxygen metabolites, as an index of systemic antioxidant potential, from baseline gradually decreased as the day passed. However, HW suppressed the reduction in biological antioxidant potential/diacron-reactive oxygen metabolites observed in PW. Drinking HW contributed to the maintenance of the redox status during consecutive days of strenuous exercise and might help prevent accumulative muscular fatigue. The study was approved by the Human Research Ethics Committee of the University of Yamanashi, Japan (approval No. H26-008) on December 17, 2014.", "conclusion": "The study was approved by the Human Research Ethics Committee of the University of Yamanashi, Japan (approval No. H26-008) on December 17, 2014." }, { "pmid": "32108985", "year": 2020, "title": "Hydrogen exerts neuroprotection by activation of the miR-21/PI3K/AKT/GSK-3β pathway in an in vitro model of traumatic brain injury.", "title_en": null, "title_de": "Wasserstoff übt Neuroprotektion durch Aktivierung des miR-21/PI3K/AKT/GSK-3β-Signalwegs in einem In-vitro-Modell des Schädel-Hirn-Traumas aus.", "journal": "Journal of cellular and molecular medicine", "authors": "Wang et al.", "author_search": "wang wang", "doi": "10.1111/jcmm.15051", "doi_url": "https://doi.org/10.1111/jcmm.15051", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32108985/", "url": "https://h2medicine.org/studies/study-wang-2020-exerts-neuroprotection-activation-mir/", "methods": [ "unspecified" ], "indications": [ "neurology" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2020 · Wang — Hydrogen exerts neuroprotection by activation of the miR-21/PI3K/AKT/GSK-3β pathway in an in vitro model of traumatic brain injury.", "summary": "Using scratched PC12 cells as an in-vitro model of traumatic brain injury, this study shows that hydrogen-rich medium activates the miR-21/PI3K/AKT/GSK-3β signalling pathway, reduces neuronal apoptosis, and promotes neurite regeneration. Both a miR-21 inhibitor and a PI3K blocker reversed the protective effect, confirming pathway specificity. This is a cell-culture study; results cannot be directly transferred to humans.", "assessment": "This is a cell-culture (in-vitro) study — not a human study. The miR-21/PI3K/AKT/GSK-3β pathway identified here is a plausible neuroprotective mechanism for H₂, adding to a growing body of mechanistic evidence. However, PC12 cells are a surrogate, the scratch model is simplified, and the jump from cultured cells to traumatic brain injury therapy in humans is substantial. No clinical conclusions can be drawn. The study is hypothesis-generating, not evidence of efficacy in patients.", "abstract": "Few studies have explored the effect of hydrogen on neuronal apoptosis or impaired nerve regeneration after traumatic brain injury, and the mechanisms involved in these processes are unclear. In this study, we explored neuroprotection of hydrogen-rich medium through activation of the miR-21/PI3K/AKT/GSK-3β pathway in an in vitro model of traumatic brain injury. Such model adopted PC12 cells with manual scratching. Then, injured cells were cultured in hydrogen-rich medium for 48 hours. Expression of miR-21, p-PI3K, p-Akt, p-GSK-3β, Bax and Bcl-2 was measured using RT-qPCR, Western blot analysis and immunofluorescence staining. Rate of apoptosis was determined using TUNEL staining. Neuronal regeneration was assessed using immunofluorescence staining. The results showed that hydrogen-rich medium improved neurite regeneration and inhibited apoptosis in the injured cells. Scratch injury was accompanied by up-regulation of miR-21, p-PI3K, p-Akt and p-GSK-3β. A miR-21 antagomir inhibited the expression of these four molecules, while a PI3K blocker only affected the three proteins and not miR-21. Both the miR-21 antagomir and PI3K blocker reversed the protective effect of hydrogen. In conclusion, hydrogen exerted a neuroprotective effect against neuronal apoptosis and impaired nerve regeneration through activation of miR-21/PI3K/AKT/GSK-3β signalling in this in vitro model of traumatic brain injury.", "conclusion": "Both the miR-21 antagomir and PI3K blocker reversed the protective effect of hydrogen. In conclusion, hydrogen exerted a neuroprotective effect against neuronal apoptosis and impaired nerve regeneration through activation of miR-21/PI3K/AKT/GSK-3β signalling in this in vitro model of traumatic brain injury." }, { "pmid": "32058932", "year": 2020, "title": "Molecular hydrogen attenuates sepsis-induced neuroinflammation through regulation of microglia polarization through an mTOR-autophagy-dependent pathway.", "title_en": null, "title_de": "Molekularer Wasserstoff mildert sepsisinduzierte Neuroinflammation durch Regulation der Mikroglia-Polarisierung über einen mTOR-Autophagie-abhängigen Signalweg.", "journal": "International immunopharmacology", "authors": "Zhuang et al.", "author_search": "zhuang zhuang", "doi": "10.1016/j.intimp.2020.106287", "doi_url": "https://doi.org/10.1016/j.intimp.2020.106287", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32058932/", "url": "https://h2medicine.org/studies/study-zhuang-2020-attenuates-sepsis-induced-neuroinflammation/", "methods": [ "inhalation" ], "indications": [ "neurology", "immune-system" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2020 · Zhuang — Molecular hydrogen attenuates sepsis-induced neuroinflammation through regulation of microglia polarization through an mTOR-autophagy-dependent pathway.", "summary": "In both a mouse sepsis model (cecal ligation and puncture) and LPS-stimulated BV-2 microglial cells, inhaled hydrogen reduced neuroinflammation, shifted microglia from a pro-inflammatory (M1) to an anti-inflammatory (M2) state, and improved cognitive function. The protective mechanism involved suppression of the mTOR pathway and activation of autophagy. These are animal and cell-culture results; clinical applicability in humans remains to be established.", "assessment": "This is an animal + cell-culture study — not a human trial. The combination of an in-vivo CLP mouse model with an in-vitro BV-2 cell model provides convergent mechanistic evidence for H₂ in neuroinflammation from sepsis. The mTOR-autophagy pathway is a credible and well-established target. Limitations: mouse CLP is an extreme sepsis model; BV-2 cells are a simplified microglial surrogate. Translation to human SAE is uncertain and requires clinical investigation. No clinical claims are justified from these data alone.", "abstract": "Sepsis-associated encephalopathy (SAE) is the cognitive impairment resulting from sepsis and is associated with increased morbidity and mortality. Hydrogen has emerged as a promising therapeutic agent to alleviate SAE. The mechanism, however, remains unclear. This research aimed to determine whether hydrogen alleviates SAE by regulating microglia polarization and whether it is mediated by the mammalian target of rapamycin (mTOR)-autophagy pathway. Septic models were established by cecal ligation and puncture (CLP) performed on mice. The Morris Water Maze was used to evaluate cognitive function. M1/M2 microglia polarization was assessed by immunofluorescence. Inflammatory cytokines were determined by ELISA. Septic cell models were established using BV-2 cells incubated with 1 μg/ml lipopolysaccharide (LPS). M1/M2 microglia polarization was assessed by flow cytometry. Inflammatory cytokines from culture medium supernatant were determined by ELISA, and associated protein expression levels of mTOR-autophagy pathway were assessed by Western blot. Hydrogen inhalation attenuated sepsis-induced cognitive impairment with improved escape latency, time spent in the target platform quadrant and number of times crossing the target platform. In both animal and cell research, hydrogen reduced TNF-α, IL-6 and HMGB1 levels and M1 polarization, but increased IL-10 and TGF-β levels and M2 polarization. Hydrogen treatment decreased the ratio of p-mTOR/mTOR and the expression of p62 and increased the ratio of p-AMPK/AMPK, LC3II/LC3I and the expression of TREM-2 and Beclin-1 in LPS-treated BV-2 cells. MHY1485, an mTOR activator, abolished the protective effects of hydrogen in vitro. Taken together, these results demonstrated that hydrogen attenuated sepsis-induced neuroinflammation by modulating microglia polarization, which was mediated by the mTOR-autophagy signaling pathway.", "conclusion": "MHY1485, an mTOR activator, abolished the protective effects of hydrogen in vitro. Taken together, these results demonstrated that hydrogen attenuated sepsis-induced neuroinflammation by modulating microglia polarization, which was mediated by the mTOR-autophagy signaling pathway." }, { "pmid": "32019803", "year": 2020, "title": "Syntrophy via Interspecies H2 Transfer between Christensenella and Methanobrevibacter Underlies Their Global Cooccurrence in the Human Gut.", "title_en": null, "title_de": "Syntrophie durch H₂-Transfer zwischen den Arten Christensenella und Methanobrevibacter liegt ihrem globalen gemeinsamen Vorkommen im menschlichen Darm zugrunde.", "journal": "mBio", "authors": "Ruaud et al.", "author_search": "ruaud ruaud", "doi": "10.1128/mbio.03235-19", "doi_url": "https://doi.org/10.1128/mbio.03235-19", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32019803/", "url": "https://h2medicine.org/studies/study-ruaud-2020-syntrophy-interspecies-transfer-between/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "metabolic", "sports-exercise" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2020 · Ruaud — Syntrophy via Interspecies H₂ Transfer between Christensenella and Methanobrevibacter Underlies Their Global Cooccurrence in the Human Gut.", "summary": "This microbiome study shows that gut bacteria of the genus Christensenella produce hydrogen gas (H₂) that is consumed by the archaeon Methanobrevibacter smithii — a metabolic partnership that explains why these two microbes co-occur globally and correlate with a lean body-mass index. The study is an in-vitro co-culture investigation of gut microbiome interactions; it does not study H₂ supplementation as a therapy, but illuminates the role of endogenously produced gut H₂ in shaping host metabolism.", "assessment": "This is a microbiome ecology study combining meta-analysis of metagenomes with in-vitro co-culture experiments — not a clinical H₂ supplementation trial. It illuminates the endogenous role of gut-produced H₂ in microbial cross-feeding and potentially in host energy metabolism. No direct therapeutic conclusions about H₂ supplementation can be drawn; the link between this microbial H₂ interplay and clinically meaningful outcomes (like BMI reduction) is correlational and far from established causality. Interesting mechanistic context for the broader H₂ and gut-health field.", "abstract": "Across human populations, 16S rRNA gene-based surveys of gut microbiomes have revealed that the bacterial family Christensenellaceae and the archaeal family Methanobacteriaceae cooccur and are enriched in individuals with a lean, compared to an obese, body mass index (BMI). Whether these association patterns reflect interactions between metabolic partners, as well as whether these associations play a role in the lean host phenotype with which they associate, remains to be ascertained. Here, we validated previously reported cooccurrence patterns of the two families and their association with a lean BMI with a meta-analysis of 1,821 metagenomes derived from 10 independent studies. Furthermore, we report positive associations at the genus and species levels between Christensenella spp. and Methanobrevibacter smithii, the most abundant methanogen of the human gut. By coculturing three Christensenella spp. with M. smithii, we show that Christensenella spp. efficiently support the metabolism of M. smithii via H2 production far better than Bacteroides thetaiotaomicron does. Christensenella minuta forms flocs colonized by M. smithii even when H2 is in excess. In culture with C. minuta, H2 consumption by M. smithii shifts the metabolic output of C. minuta's fermentation toward acetate rather than butyrate. Together, these results indicate that the widespread cooccurrence of these microorganisms is underpinned by both physical and metabolic interactions. Their combined metabolic activity may provide insights into their association with a lean host BMI.IMPORTANCE The human gut microbiome is made of trillions of microbial cells, most of which are Bacteria, with a subset of Archaea The bacterial family Christensenellaceae and the archaeal family Methanobacteriaceae are widespread in human guts. They correlate with each other and with a lean body type. Whether species of these two families interact and how they affect the body type are unanswered questions. Here, we show that species within these families correlate with each other across people. We also demonstrate that particular species of these two families grow together in dense flocs, wherein the bacteria provide hydrogen gas to the archaea, which then make methane. When the archaea are present, the ratio of bacterial products (which are nutrients for humans) is changed. These observations indicate that when these species grow together, their products have the potential to affect the physiology of their human host.", "conclusion": "When the archaea are present, the ratio of bacterial products (which are nutrients for humans) is changed. These observations indicate that when these species grow together, their products have the potential to affect the physiology of their human host." }, { "pmid": "31977289", "year": 2020, "title": "Untethered Soft Robotics with Fully Integrated Wireless Sensing and Actuating Systems for Somatosensory and Respiratory Functions.", "title_en": null, "title_de": "Kabellose weiche Robotik mit vollständig integrierten drahtlosen Sensor- und Aktuatorsystemen für somatosensorische und respiratorische Funktionen.", "journal": "Soft robotics", "authors": "Oh et al.", "author_search": "oh oh", "doi": "10.1089/soro.2019.0066", "doi_url": "https://doi.org/10.1089/soro.2019.0066", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31977289/", "url": "https://h2medicine.org/studies/study-oh-2020-untethered-soft-robotics-fully/", "methods": [ "inhalation" ], "indications": [ "respiratory" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2020 · Oh — Untethered Soft Robotics with Fully Integrated Wireless Sensing and Actuating Systems for Somatosensory and Respiratory Functions.", "summary": "This engineering study presents a wireless soft robotic hand that integrates flexible sensors — including a hydrogen gas sensor — for monitoring tactile pressure, temperature, and H₂ concentration via smartphone. The paper is a robotics/electronics engineering publication; molecular hydrogen (H₂) appears only as one of several gases the sensor detects. This study has no relevance to H₂ as a biomedical or therapeutic agent.", "assessment": "This paper has no relevance to H₂ medicine. It is a robotics engineering publication in which H₂ gas detection is one technical feature among several. No therapeutic, biological, or biomedical conclusions about molecular hydrogen can be drawn from this study. It should not be interpreted in the context of H₂ supplementation or hydrogen health effects.", "abstract": "There has been a great deal of interest in designing soft robots that can mimic a human system with haptic and proprioceptive functions. There is now a strong demand for soft robots that can sense their surroundings and functions in harsh environments. This is because the wireless sensing and actuating capabilities of these soft robots are very important for monitoring explosive gases in disaster areas and for moving through contaminated environments. To develop these wireless systems, complex electronic circuits must be integrated with various sensors and actuators. However, the conventional electronic circuits based on silicon are rigid and fragile, which can limit their reliable integration with soft robots for achieving continuous locomotion. In our study, we developed an untethered, soft robotic hand that mimics human fingers. The soft robotic fingers are composed of a thermally responsive elastomer composite that includes capsules of ethanol and liquid metals for its shape deformation through an electrothermal phase transition. And these soft actuators are integrated fully with flexible forms of heaters, with pressure, temperature, and hydrogen gas sensors, and wireless electronic circuits. Entire functions of this soft hand, including the gripping motion of soft robotic fingers and the real-time detections of tactile pressures, temperatures, and hydrogen gas concentrations, are monitored or controlled wirelessly using a smartphone. This wireless sensing and actuating system for somatosensory and respiratory functions of a soft robot provides a promising strategy for next-generation robotics.", "conclusion": "Entire functions of this soft hand, including the gripping motion of soft robotic fingers and the real-time detections of tactile pressures, temperatures, and hydrogen gas concentrations, are monitored or controlled wirelessly using a smartphone. This wireless sensing and actuating system for somatosensory and respiratory functions of a soft robot provides a promising strategy for next-generation " }, { "pmid": "31930571", "year": 2020, "title": "Molecular hydrogen regulates PTEN-AKT-mTOR signaling via ROS to alleviate peritoneal dialysis-related peritoneal fibrosis.", "title_en": null, "title_de": "Molekularer Wasserstoff reguliert die PTEN-AKT-mTOR-Signalübertragung über ROS, um die mit der Peritonealdialyse verbundene peritoneale Fibrose zu lindern.", "journal": "FASEB journal : official publication of the Federation of American Societies for Experimental Biology", "authors": "Lu et al.", "author_search": "lu lu", "doi": "10.1096/fj.201901981r", "doi_url": "https://doi.org/10.1096/fj.201901981r", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31930571/", "url": "https://h2medicine.org/studies/study-lu-2020-regulates-pten-akt-mtor/", "methods": [ "saline-iv" ], "indications": [ "kidney-dialysis", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2020 · Lu — Molecular hydrogen regulates PTEN-AKT-mTOR signaling via ROS to alleviate peritoneal dialysis-related peritoneal fibrosis.", "summary": "In mice treated with high-glucose dialysate to induce peritoneal fibrosis, and in MeT-5A mesothelial cells in culture, hydrogen-rich peritoneal dialysate inhibited fibrosis by eliminating intracellular reactive oxygen species (ROS) and suppressing the PTEN/AKT/mTOR signalling pathway. These results are encouraging for dialysis patients at risk of peritoneal fibrosis, but remain animal and cell-culture findings — no human data are provided.", "assessment": "This is an animal + cell-culture (in-vitro) study — not a clinical trial. The mechanism is plausible and the delivery route (H₂ dissolved in dialysate) is clinically relevant. Limitations: the mouse model and MeT-5A cells are simplified; chronic human peritoneal dialysis involves complex biological changes not captured here. The authors' claim of „great clinical significance“ is premature without human data. This is hypothesis-generating and mechanistically credible, but no clinical conclusions for dialysis patients can be drawn.", "abstract": "As a convenient, effective and economical kidney replacement therapy for end-stage renal disease (ESRD), peritoneal dialysis is available in approximately 11% of ESRD patients worldwide. However, long-term peritoneal dialysis treatment causes peritoneal fibrosis. In recent years, the application potential of molecular hydrogen in the biomedicine has been well recognized. Molecular hydrogen selectively scavenges cytotoxic reactive oxygen species (ROS) and acts as an antioxidant. In this experiment, a high glucose-induced peritoneal fibrosis mouse model was successfully established by intraperitoneal injection of high glucose peritoneal dialysate, and peritoneal fibrosis mice were treated with hydrogen-rich peritoneal dialysate. In addition, in vitro studies of high glucose-induced peritoneal fibrosis were performed using MeT-5A cells. In vitro and in vivo experiments show that molecular hydrogen could inhibit peritoneal fibrosis progress induced by high glucose effectively. Furthermore, it has been found that molecular hydrogen alleviate fibrosis by eliminating intracellular ROS and inhibiting the activation of the PTEN/AKT/mTOR pathway. The present data proposes that molecular hydrogen exerts the capacity of anti-peritoneal fibrosis through the ROS/PTEN/AKT/mTOR pathway. Therefore, molecule hydrogen is a potential, safe, and effective treatment agent, with peritoneal protective property and great clinical significance.", "conclusion": "The present data proposes that molecular hydrogen exerts the capacity of anti-peritoneal fibrosis through the ROS/PTEN/AKT/mTOR pathway. Therefore, molecule hydrogen is a potential, safe, and effective treatment agent, with peritoneal protective property and great clinical significance." }, { "pmid": "31924176", "year": 2020, "title": "Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway.", "title_en": null, "title_de": "Wasserstoff hemmt das Wachstum des Endometriumkarzinoms über einen ROS/NLRP3/Caspase-1/GSDMD-vermittelten pyroptotischen Signalweg.", "journal": "BMC cancer", "authors": "Yang et al.", "author_search": "yang yang", "doi": "10.1186/s12885-019-6491-6", "doi_url": "https://doi.org/10.1186/s12885-019-6491-6", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31924176/", "url": "https://h2medicine.org/studies/study-yang-2020-inhibits-endometrial-cancer-growth/", "methods": [ "drinking-hrw" ], "indications": [ "cancer", "immune-system" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2020 · Yang — Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway.", "summary": "In endometrial cancer cell lines and a xenograft mouse model, hydrogen-rich water increased reactive oxygen species (ROS) in cancer cells, activated the NLRP3 inflammasome/GSDMD pyroptosis pathway, and suppressed tumour growth. This is an in-vitro and animal study — the paradoxical pro-oxidant effect of H₂ specifically in tumour cells is the central finding, but no clinical evidence in cancer patients exists.", "assessment": "This is an in-vitro and animal xenograft study — not a clinical trial. The pyroptosis mechanism through which H₂ may selectively kill cancer cells is scientifically interesting and adds to mechanistic understanding. Key limitations: the pro-oxidant effect of H₂ in cancer cells versus its antioxidant effect in healthy cells needs more explanation; xenograft models are artificial; clinical safety and efficacy in endometrial cancer patients are entirely unknown. No therapeutic claims about H₂ for cancer treatment can be supported by this data alone.", "abstract": "BACKGROUND: Pyroptosis belongs to a novel inflammatory programmed cell death pathway, with the possible prognosis of endometrial cancer related to the terminal protein GSDMD. Hydrogen exerts a biphasic effect on cancer by promoting tumor cell death and protecting normal cells, which might initiate GSDMD pathway-mediated pyroptosis. METHODS: We performed immunohistochemical staining and western immunoblotting analysis to observe expression of NLRP3, caspase-1, and GSDMD in human and xenograft mice endometrial cancer tissue and cell lines. We investigated treatment with hydrogen could boost ROS accumulation in endometrial cancer cells by intracellular and mitochondrial sources. GSDMD shRNA lentivirus was used to transfect endometrial cancer cells to investigate the function of GSDMD protein in pyroptosis. Propidium iodide (PI) staining, TUNEL assay, measurement of lactate dehydrogenase (LDH) release and IL-1β ELISA were used to analysis pyroptosis between hydrogen-supplemented or normal culture medium. We conducted in vivo human endometrial tumor xenograft mice model to observe anti-tumor effect in hydrogen supplementation. RESULTS: We observed overexpression of NLRP3, caspase-1, and GSDMD in human endometrial cancer and cell lines by IHC and western immunoblotting. Hydrogen pretreatment upregulated ROS and the expression of pyroptosis-related proteins, and increased the number of PI- and TUNEL-positive cells, as well as the release of LDH and IL-1β, however, GSDMD depletion reduced their release. We further demonstrated that hydrogen supplementation in mice was sufficient for the anti-tumor effect to inhibit xenograft volume and weight of endometrial tumors, as mice subjected to hydrogen-rich water displayed decreased radiance. Tumor tissue sections in the HRW groups presented moderate-to-strong positive expression of NLRP3, caspase-1 and GSDMD. Hydrogen attenuated tumor volume and weight in a xenograft mouse model though the pyroptotic pathway. CONCLUSIONS: This study extended our original analysis of the ability of hydrogen to stimulate NLRP3 inflammasome/GSDMD activation in pyroptosis and revealed possible mechanism (s) for improvement of anti-tumor effects in the clinical management of endometrial cancer.", "conclusion": "This study extended our original analysis of the ability of hydrogen to stimulate NLRP3 inflammasome/GSDMD activation in pyroptosis and revealed possible mechanism (s) for improvement of anti-tumor effects in the clinical management of endometrial cancer." }, { "pmid": "31810604", "year": 2020, "title": "Molecular hydrogen suppresses superoxide generation in the mitochondrial complex I and reduced mitochondrial membrane potential.", "title_en": null, "title_de": "Molekularer Wasserstoff unterdrückt die Superoxidbildung im mitochondrialen Komplex I und senkt das mitochondriale Membranpotenzial.", "journal": "Biochemical and biophysical research communications", "authors": "Ishihara et al.", "author_search": "ishihara ishihara", "doi": "10.1016/j.bbrc.2019.11.135", "doi_url": "https://doi.org/10.1016/j.bbrc.2019.11.135", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31810604/", "url": "https://h2medicine.org/studies/study-ishihara-2020-suppresses-superoxide-generation-mitochondrial/", "methods": [ "unspecified" ], "indications": [ "sports-exercise", "neurology", "joints-rheumatology", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2020 · Ishihara — Molecular hydrogen suppresses superoxide generation in the mitochondrial complex I and reduced mitochondrial membrane potential.", "summary": "In isolated mitochondria and cultured cells, molecular hydrogen altered the direction of electron flow at complex I, suppressed superoxide generation by 51 %, and reduced mitochondrial membrane potential by 11 %. This in-vitro study provides a mechanistic account of how H₂ may reduce oxidative damage at the mitochondrial level — a finding distinct from the classical hydroxyl-radical scavenging hypothesis. Results are preliminary and limited to isolated systems.", "assessment": "This is an in-vitro mechanistic study using isolated mitochondria and cultured cells — not an animal or human study. The proposed electron-flow mechanism adds a credible layer to H₂'s antioxidant story, going beyond classical hydroxyl-radical scavenging. Limitations: isolated mitochondria and single cell lines cannot capture the complexity of in-vivo redox biology; the H₂ concentration used (25 µM) may exceed what is achievable in target tissues; the physiological relevance of membrane potential changes needs contextualisation. This is mechanistically interesting but hypothesis-generating only.", "abstract": "Molecular hydrogen (H2) is recognized as a medical gas applicable to numerous diseases including neurodegenerative diseases, metabolic disorders, and rheumatoid arthritis. Although the efficacy of H2 is reportedly attributed to its scavenging capability against the hydroxyl radical, the mechanisms underlying its therapeutic efficacy are not fully understood. Herein, we estimated the role of H2 in the energy converting system of the mitochondria, the source of reactive oxygen species. To investigate the effects of H2 on mitochondrial function, direction of electron flow, superoxide generation, and mitochondrial membrane potential were investigated. Forward electron transport (FET) or reverse electron transport (RET) was assessed by monitoring the decrease or increase of β-nicotinamide adenine dinucleotide hydrate (NADH, - or +, μM, respectively) in the presence of β-nicotinamide adenine dinucleotide (NAD+) and/or succinate in the isolated mitochondria. H2O2 converted from superoxide by superoxide dismutase (SOD) was measured to estimate electron leakage in the mitochondria. The effects of H2 on mitochondrial membrane potential were observed by staining cells with the fluorescence probe, teramethylrhodamine ethyl ester (TMRE). Despite the absence of succinate, a distinct RET was observed (from +0.0313 ± 0.0106 μM to +1.20 ± 0.302 μM) by adding 25 μM H2. In the presence of 5 μM NADH, RET by succinate inverted to FET from +1.62 ± 0.358 μM to -1.83 ± 0.191 μM, accompanied by a suppression of superoxide generated predominantly from complex I by 51.1%. H2 solely reduced mitochondrial membrane potential of the cultured cells by 11.3% as assessed by TMRE. The direction of electron flow was altered by H2 depending on the NAD+/NADH ratio, accompanied by suppression of superoxide generation H2 could suppress superoxide generation in complex I in vitro and reduce membrane potential in vivo. H2 may also neutralize semiquinone radicals to reduce superoxide produced in complex III. H2 may function as a rectifier of the electron flow affecting the mitochondrial membrane potential to suppress oxidative damage in mitochondria.", "conclusion": "H2 may also neutralize semiquinone radicals to reduce superoxide produced in complex III. H2 may function as a rectifier of the electron flow affecting the mitochondrial membrane potential to suppress oxidative damage in mitochondria." }, { "pmid": "31746358", "year": 2020, "title": "Protective effects of hydrogen‑rich saline against experimental diabetic peripheral neuropathy via activation of the mitochondrial ATP‑sensitive potassium channel channels in rats.", "title_en": null, "title_de": "Schützende Wirkungen von wasserstoffreicher Kochsalzlösung gegen experimentelle diabetische periphere Neuropathie über die Aktivierung mitochondrialer ATP-sensitiver Kaliumkanäle bei Ratten.", "journal": "Molecular medicine reports", "authors": "Jiao et al.", "author_search": "jiao jiao", "doi": "10.3892/mmr.2019.10795", "doi_url": "https://doi.org/10.3892/mmr.2019.10795", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31746358/", "url": "https://h2medicine.org/studies/study-jiao-2020-protective-saline-against-experimental/", "methods": [ "saline-iv", "drinking-hrw" ], "indications": [ "diabetes", "neurology", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2020 · Jiao — Protective effects of hydrogen-rich saline against experimental diabetic peripheral neuropathy via activation of the mitochondrial ATP-sensitive potassium channel in rats.", "summary": "In streptozotocin-induced diabetic rats, hydrogen-rich saline injected intraperitoneally for four weeks reduced behavioural, biochemical, and molecular markers of diabetic peripheral neuropathy (DPN), with effects partially mediated through mitochondrial ATP-sensitive potassium (Mito-K-ATP) channels. This is an animal study in rats; the findings are promising but not transferable to humans without clinical trials.", "assessment": "This is an animal study (rats) — not a clinical trial. The Mito-K-ATP channel mechanism identified here is a credible addition to the understanding of H₂ in diabetic neuropathy. The multi-parameter assessment (behaviour, biochemistry, molecular markers) is a strength. Limitations: STZ-induced diabetes in rats differs substantially from human DPN; intraperitoneal injection is not a standard clinical H₂ delivery route; partial reversal by 5-HD means the full mechanism is not yet elucidated. No clinical conclusions for human DPN treatment can be drawn. This study supports further preclinical and eventually clinical investigation.", "abstract": "It has previously been demonstrated that hyperglycemia‑induced oxidative stress and inflammation are closely associated with the development of diabetic complications, including diabetic neuropathy. Additionally, mitochondrial ATP‑sensitive potassium (Mito‑K‑ATP) channels play a homeostatic role on blood glucose regulation in organisms. Molecular hydrogen (H2) exhibits anti‑inflammatory, anti‑antioxidative and anti‑apoptotic properties and can be used to treat more than 71 diseases safely. In addition, the diabetes animal models which are set up using streptozotocin (STZ) injection, is a type of high long‑term stability, low animal mortality rate and security method. The aim of the current study was to assess the value of hydrogen‑rich saline (HS) in diabetic peripheral neuropathy (DPN) treatment and to determine its associated mechanisms in STZ‑induced diabetic experimental rats. Additionally, the effects of the Mito‑K‑ATP channels, oxidative stress, inflammatory cytokines and apoptosis on DPN were also evaluated. From week 5 of STZ injections, HS (2.5, 5 and 10 ml/kg) was injected into the rat abdominal cavity every day for a period of 4 weeks. The results of the current study demonstrated that HS significantly reduced behavioral, biochemical and molecular effects caused by DPN. However, 5‑hydroxydecanoate, a selective Mito‑K‑ATP channels general pathway inhibitor, partially eliminated the therapeutic effect of HS on DPN. These results indicated that the use of HS may be a novel strategy to treat DPN by activating the Mito‑K‑ATP pathway and reducing oxidative stress, inflammatory cytokines and apoptosis.", "conclusion": "However, 5‑hydroxydecanoate, a selective Mito‑K‑ATP channels general pathway inhibitor, partially eliminated the therapeutic effect of HS on DPN. These results indicated that the use of HS may be a novel strategy to treat DPN by activating the Mito‑K‑ATP pathway and reducing oxidative stress, inflammatory cytokines and apoptosis." }, { "pmid": "32029879", "year": 2020, "title": "Hydrogen Attenuates Allergic Inflammation by Reversing Energy Metabolic Pathway Switch", "title_en": null, "title_de": "Wasserstoff dämpft allergische Entzündung durch Umkehr eines Umschaltens im Energiestoffwechsel", "journal": "Scientific Reports", "authors": "Niu et al.", "author_search": "niu niu", "doi": "10.1038/s41598-020-58999-0", "doi_url": "https://doi.org/10.1038/s41598-020-58999-0", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32029879/", "url": "https://h2medicine.org/studies/study-niu-2020-allergic-inflammation-energy-metabolic-pathway/", "methods": [ "unspecified" ], "indications": [ "allergy", "respiratory", "mechanism", "immune-system" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2020 · Niu — Hydrogen Attenuates Allergic Inflammation by Reversing Energy Metabolic Pathway Switch", "summary": "Hydrogen curbs allergic airway inflammation by resetting a disturbed energy metabolism of the immune cells. In asthma patients and in the asthma mouse model, metabolism had switched from healthy cellular respiration to fermentation — H₂ reversed this switch and mitigated the inflammation. (Scientific Reports, 2020.)", "assessment": "Valuable as a mechanism study: it goes beyond the classical „H₂ = antioxidant“ picture and shows that hydrogen can reprogram the energy metabolism of immune cells — a modern explanatory approach for the anti-inflammatory effect in allergy and asthma. For us it provides a deeper „why“ behind the observations in airway and allergy applications. Limitations, stated honestly: this is a purely preclinical investigation (human monocytes in the lab + ovalbumin mouse model, no treatment outcome in patients). The study is listed as an observational study; statements on clinical symptom improvement in humans cannot be derived from it. Mechanistically it flanks the small human pilot study on nasal lavage in allergic rhinitis.", "abstract": "Mechanisms mediating the protective effects of molecular hydrogen (H2) are not well understood. This study explored the possibility that H2 exerts its anti-inflammatory effect by modulating energy metabolic pathway switch. Activities of glycolytic and mitochondrial oxidative phosphorylation systems were assessed in asthmatic patients and in mouse model of allergic airway inflammation. The effects of hydrogen treatment on airway inflammation and on changes in activities of these two pathways were evaluated. Monocytes from asthmatic patients and lungs from ovalbumin-sensitized and challenged mice had increased lactate production and glycolytic enzyme activities (enhanced glycolysis), accompanied by decreased ATP production and mitochondrial respiratory chain complex I and III activities (suppressed mitochondrial oxidative phosphorylation), indicating an energy metabolic pathway switch. Treatment of ovalbumin-sensitized and challenged mice with hydrogen reversed the energy metabolic pathway switch, and mitigated airway inflammation. Hydrogen abrogated ovalbumin sensitization and challenge-induced upregulation of glycolytic enzymes and hypoxia-inducible factor-1α, and downregulation of mitochondrial respiratory chain complexes and peroxisome proliferator activated receptor-γ coactivator-1α. Hydrogen abrogated ovalbumin sensitization and challenge-induced sirtuins 1, 3, 5 and 6 downregulation. Our data demonstrates that allergic airway inflammation is associated with an energy metabolic pathway switch from oxidative phosphorylation to aerobic glycolysis. Hydrogen inhibits airway inflammation by reversing this switch. Hydrogen regulates energy metabolic reprogramming by acting at multiple levels in the energy metabolism regulation pathways.", "conclusion": "Hydrogen inhibits airway inflammation by reversing this switch. Hydrogen regulates energy metabolic reprogramming by acting at multiple levels in the energy metabolism regulation pathways." }, { "pmid": "31267691", "year": 2019, "title": "Micro/Nanomaterials-Augmented Hydrogen Therapy", "title_en": null, "title_de": "Durch Mikro-/Nanomaterialien verstärkte Wasserstofftherapie", "journal": "Advanced Healthcare Materials", "authors": "Zhou et al.", "author_search": "zhou zhou", "doi": "10.1002/adhm.201900463", "doi_url": "https://doi.org/10.1002/adhm.201900463", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31267691/", "url": "https://h2medicine.org/studies/study-zhou-2019-nanomaterials-augmented-therapy/", "methods": [ "inhalation" ], "indications": [ "fundamentals", "oxidative-stress", "cancer" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2019 · Zhou — Micro/Nanomaterials-Augmented Hydrogen Therapy", "summary": "Nanomedicine for hydrogen: H₂ works in oxidative-inflammatory diseases, but diffuses without direction and dissolves poorly in water. This review article shows how micro/nanomaterials can deliver H₂ to the target, release it in a controlled way, and amplify its effect. (Advanced Healthcare Materials, 2019.)", "assessment": "A useful review that does two things at once: it reaffirms the strong safety profile of H₂ (no blood poisoning even at high concentration) and openly names the pharmacological weakness (low solubility, aimless diffusion). For us this is doubly valuable — the safety argument is directly usable, the limitation helps stay realistic. The nanomaterial strategies presented, however, are research concepts, far removed from everyday H₂ water. Limitation, stated honestly: narrative review/concept paper (evidence level 4), no own data, no proof of clinical benefit; the described nano approaches are experimental.", "abstract": "Hydrogen therapy is an emerging and promising therapy strategy of using molecular hydrogen as a new type of safe and effective therapeutic agent, exhibiting remarkable therapeutic effects on many oxidative stress-/inflammation-related diseases owing to its bio-reductivity and homeostatic regulation ability. Different from other gaseous transmitters such as NO, CO, and H2 S, hydrogen gas has no blood poisoning risk at high concentration because it does not affect the oxygen-carrying behavior of blood red cells. Hydrogen molecules also have low aqueous solubility and high but aimless diffusibility, causing limited therapy efficacy in many diseases. To realize the site-specific hydrogen delivery, controlled hydrogen release and combined therapy is significant but still challenging. Here, a concept of hydrogen nanomedicine to address the issues of hydrogen medicine by using functional micro/nanomaterials for augmented hydrogen therapy is proposed. In this review, various strategies of micro/nanomaterials-augmented hydrogen therapy, including micro/nanomaterials-mediated targeted hydrogen delivery, controlled hydrogen release, and nanocatalytic and multimodel enhancement of hydrogen therapy efficacy, are summarized, which can open a new window for treatment of inflammation-related diseases.", "conclusion": "Here, a concept of hydrogen nanomedicine to address the issues of hydrogen medicine by using functional micro/nanomaterials for augmented hydrogen therapy is proposed. In this review, various strategies of micro/nanomaterials-augmented hydrogen therapy, including micro/nanomaterials-mediated targeted hydrogen delivery, controlled hydrogen release, and nanocatalytic and multimodel enhancement of hy" }, { "pmid": "31871547", "year": 2019, "title": "Medical Application of Hydrogen in Hematological Diseases.", "title_en": null, "title_de": "Medizinische Anwendung von Wasserstoff bei hämatologischen Erkrankungen.", "journal": "Oxidative medicine and cellular longevity", "authors": "Qian et al.", "author_search": "qian qian", "doi": "10.1155/2019/3917393", "doi_url": "https://doi.org/10.1155/2019/3917393", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31871547/", "url": "https://h2medicine.org/studies/study-qian-2019-medical-application-hematological-diseases/", "methods": [ "inhalation" ], "indications": [ "diabetes", "cardiovascular", "cancer", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2019 · Qian — Medical Application of Hydrogen in Hematological Diseases.", "summary": "This review article surveys the clinical and basic research on molecular hydrogen in haematological diseases, including graft-versus-host disease (GvHD) after stem cell transplantation, and summarises H₂'s established antioxidant, anti-inflammatory, and anti-apoptotic properties. As a literature review, it synthesises findings from others' studies; it does not present new experimental data. The authors themselves have previously studied H₂ in GvHD.", "assessment": "This is a narrative review — not an original experiment. It provides a useful overview of where H₂ medicine intersects with haematology, with a specific focus on GvHD and radiation injury. Limitations of reviews apply: no new data, possible selective citation, and the authors are not neutral (they have their own H₂/GvHD research programme). For the specialised area of GvHD after stem cell transplantation, the claim that H₂ has been „proven“ effective is strong language that requires individual evaluation of the cited primary studies. The review is informative as an orientation but cannot substitute for systematic reviews or meta-analyses.", "abstract": "Hydrogen gas has been reported to have medical efficacy since the 1880s. Still, medical researchers did not pay much attention to hydrogen gas until the 20th century. Recent research, both basic and clinical, has proven that hydrogen is an important physiological regulatory factor with antioxidative, anti-inflammatory, and antiapoptotic effects. In the past two decades, more than 1000 papers have been published on the topic, including organ ischemia-reperfusion injury, radiation injury, diabetes, atherosclerosis, hypertension, or cancer. We have previously hypothesized and proven the therapeutic effects of hydrogen gas in graft-versus-host disease following stem cell transplantation. In the current manuscript, we present the clinical advances of hydrogen gas in hematological disorders.", "conclusion": "We have previously hypothesized and proven the therapeutic effects of hydrogen gas in graft-versus-host disease following stem cell transplantation. In the current manuscript, we present the clinical advances of hydrogen gas in hematological disorders." }, { "pmid": "31509764", "year": 2019, "title": "Myalgic encephalomyelitis/chronic fatigue syndrome: From pathophysiological insights to novel therapeutic opportunities.", "title_en": null, "title_de": "Myalgische Enzephalomyelitis/chronisches Erschöpfungssyndrom: Von pathophysiologischen Erkenntnissen zu neuartigen therapeutischen Möglichkeiten.", "journal": "Pharmacological research", "authors": "Morris et al.", "author_search": "morris morris", "doi": "10.1016/j.phrs.2019.104450", "doi_url": "https://doi.org/10.1016/j.phrs.2019.104450", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31509764/", "url": "https://h2medicine.org/studies/study-morris-2019-myalgic-encephalomyelitis-chronic-fatigue/", "methods": [ "unspecified" ], "indications": [ "sports-exercise", "neurology", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2019 · Morris — Myalgic encephalomyelitis/chronic fatigue syndrome: From pathophysiological insights to novel therapeutic opportunities.", "summary": "This review maps the multiple pathophysiological abnormalities described in ME/CFS — including chronic inflammation, oxidative and nitrosative stress, gut barrier disruption, and mitochondrial dysfunction — and identifies several candidate therapeutic agents, among them molecular hydrogen, that target these pathways. The paper does not present new experimental data; it synthesises existing evidence and frames hydrogen as one of several „promising yet preliminary“ options for this poorly-treated condition.", "assessment": "This is a narrative review — not a clinical trial or experimental study. Molecular hydrogen is one of several candidate agents discussed in the context of ME/CFS pathophysiology; no H₂-specific clinical trial in ME/CFS patients is cited. Limitations: narrative reviews can be selective; no pooled effect data; ME/CFS is a heterogeneous condition and any generalisation is difficult. The authors themselves call the evidence „preliminary.“ This review supports the biological plausibility of H₂ for ME/CFS-relevant pathways, but no clinical conclusions about H₂ treatment for ME/CFS can be drawn from a review alone.", "abstract": "Myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS) is a common and disabling condition with a paucity of effective and evidence-based therapies, reflecting a major unmet need. Cognitive behavioural therapy and graded exercise are of modest benefit for only some ME/CFS patients, and many sufferers report aggravation of symptoms of fatigue with exercise. The presence of a multiplicity of pathophysiological abnormalities in at least the subgroup of people with ME/CFS diagnosed with the current international consensus \"Fukuda\" criteria, points to numerous potential therapeutic targets. Such abnormalities include extensive data showing that at least a subgroup has a pro-inflammatory state, increased oxidative and nitrosative stress, disruption of gut mucosal barriers and mitochondrial dysfunction together with dysregulated bioenergetics. In this paper, these pathways are summarised, and data regarding promising therapeutic options that target these pathways are highlighted; they include coenzyme Q10, melatonin, curcumin, molecular hydrogen and N-acetylcysteine. These data are promising yet preliminary, suggesting hopeful avenues to address this major unmet burden of illness.", "conclusion": "In this paper, these pathways are summarised, and data regarding promising therapeutic options that target these pathways are highlighted; they include coenzyme Q10, melatonin, curcumin, molecular hydrogen and N-acetylcysteine. These data are promising yet preliminary, suggesting hopeful avenues to address this major unmet burden of illness." }, { "pmid": "31159153", "year": 2019, "title": "A New Approach for the Prevention and Treatment of Cardiovascular Disorders. Molecular Hydrogen Significantly Reduces the Effects of Oxidative Stress.", "title_en": null, "title_de": "Ein neuer Ansatz zur Prävention und Behandlung kardiovaskulärer Erkrankungen. Molekularer Wasserstoff reduziert die Auswirkungen von oxidativem Stress signifikant.", "journal": "Molecules (Basel, Switzerland)", "authors": "LeBaron et al.", "author_search": "lebaron le baron", "doi": "10.3390/molecules24112076", "doi_url": "https://doi.org/10.3390/molecules24112076", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31159153/", "url": "https://h2medicine.org/studies/study-lebaron-2019-approach-prevention-cardiovascular-disorders/", "methods": [ "inhalation", "saline-iv", "drinking-hrw" ], "indications": [ "neurology", "cardiovascular", "cancer", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2019 · LeBaron et al. — A New Approach for the Prevention and Treatment of Cardiovascular Disorders. Molecular Hydrogen Significantly Reduces the Effects of Oxidative Stress.", "summary": "Molecular hydrogen (H₂) has been studied in preclinical and clinical settings for a wide range of cardiovascular conditions linked to oxidative stress and inflammation. It can be administered via inhalation, hydrogen-rich water, or hydrogen-rich saline and favorably modulates inflammatory signalling. This 2019 review by LeBaron and colleagues surveys the available evidence and discusses the unique biological profile of H₂ — including a hormetic-like effect that may partly explain its benefits.", "assessment": "This is a review article (no new experimental data), synthesising preclinical and clinical studies on H₂ for cardiovascular and related conditions. Its strength lies in breadth of coverage and the honest acknowledgement that mechanisms are not yet fully understood. Limitations: narrative reviews can be selectively cited; effect sizes are not pooled; several cited studies are animal experiments not directly applicable to humans. The hormesis remark is scientifically interesting but remains speculative. LeBaron's affiliation with the Molecular Hydrogen Institute is a declared interest context readers should weigh.", "abstract": "Cardiovascular diseases are the most common causes of morbidity and mortality worldwide. Redox dysregulation and a dyshomeostasis of inflammation arise from, and result in, cellular aberrations and pathological conditions, which lead to cardiovascular diseases. Despite years of intensive research, there is still no safe and effective method for their prevention and treatment. Recently, molecular hydrogen has been investigated in preclinical and clinical studies on various diseases associated with oxidative and inflammatory stress such as radiation-induced heart disease, ischemia-reperfusion injury, myocardial and brain infarction, storage of the heart, heart transplantation, etc. Hydrogen is primarily administered via inhalation, drinking hydrogen-rich water, or injection of hydrogen-rich saline. It favorably modulates signal transduction and gene expression resulting in suppression of proinflammatory cytokines, excess ROS production, and in the activation of the Nrf2 antioxidant transcription factor. Although H2 appears to be an important biological molecule with anti-oxidant, anti-inflammatory, and anti-apoptotic effects, the exact mechanisms of action remain elusive. There is no reported clinical toxicity; however, some data suggests that H2 has a mild hormetic-like effect, which likely mediate some of its benefits. The mechanistic data, coupled with the pre-clinical and clinical studies, suggest that H2 may be useful for ROS/inflammation-induced cardiotoxicity and other conditions.", "conclusion": "There is no reported clinical toxicity; however, some data suggests that H2 has a mild hormetic-like effect, which likely mediate some of its benefits. The mechanistic data, coupled with the pre-clinical and clinical studies, suggest that H2 may be useful for ROS/inflammation-induced cardiotoxicity and other conditions." }, { "pmid": "31100203", "year": 2019, "title": "Circulating messenger for neuroprotection induced by molecular hydrogen.", "title_en": null, "title_de": "Zirkulierender Botenstoff für die durch molekularen Wasserstoff induzierte Neuroprotektion.", "journal": "Canadian journal of physiology and pharmacology", "authors": "Noda et al.", "author_search": "noda noda", "doi": "10.1139/cjpp-2019-0098", "doi_url": "https://doi.org/10.1139/cjpp-2019-0098", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31100203/", "url": "https://h2medicine.org/studies/study-noda-2019-circulating-messenger-neuroprotection-induced/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise", "neurology", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2019 · Noda et al. — Circulating messenger for neuroprotection induced by molecular hydrogen.", "summary": "Drinking hydrogen-rich water does not only act while H₂ is present in the body — it can trigger lasting neuroprotection through an indirect hormonal mechanism involving ghrelin. This 2019 review by Noda and colleagues explains how H₂ in drinking water stimulates ghrelin release from the stomach, which then crosses the blood-brain barrier and activates neuroprotective pathways — even after H₂ itself has left the body.", "assessment": "This is a review of preclinical (animal and cell-line) research. The ghrelin-mediated indirect neuroprotection hypothesis is scientifically interesting and distinguishes H₂ from a simple antioxidant supplement. Limitations: all mechanistic data cited are from rodent models and a ghrelin-producing cell line — not from humans. Whether this indirect pathway operates in people, at the H₂ doses achievable through drinking, remains to be demonstrated. Translating animal Parkinson's models to human neuroprotection is notoriously difficult. This is a hypothesis-generating review, not clinical proof.", "abstract": "Molecular hydrogen (H2) showed protection against various kinds of oxidative-stress-related diseases. First, it was reported that the mechanism of therapeutic effects of H2 was antioxidative effect due to inhibition of the most cytotoxic reactive oxygen species, hydroxy radical (•OH). However, after chronic administration of H2 in drinking water, oxidative-stress-induced nerve injury is significantly attenuated even in the absence of H2. It suggests indirect signaling of H2 and gastrointestinal tract is involved. Indirect effects of H2 could be tested by giving H2 water only before nerve injury, as preconditioning. For example, preconditioning of H2 for certain a period (∼7 days) in Parkinson's disease model mice shows significant neuroprotection. As the mechanism of indirect effect, H2 in drinking water induces ghrelin production and release from the stomach via β1-adrenergic receptor stimulation. Released ghrelin circulates in the body, being transported across the blood-brain barrier, activates its receptor, growth-hormone secretagogue receptor. H2-induced upregulation of ghrelin mRNA is also shown in ghrelin-producing cell line, SG-1. These observations help with understanding the chronic effects of H2 and raise intriguing preventive and therapeutic options using H2.", "conclusion": "H2-induced upregulation of ghrelin mRNA is also shown in ghrelin-producing cell line, SG-1. These observations help with understanding the chronic effects of H2 and raise intriguing preventive and therapeutic options using H2." }, { "pmid": "31057105", "year": 2019, "title": "Therapeutic Efficacy of Molecular Hydrogen: A New Mechanistic Insight.", "title_en": null, "title_de": "Therapeutische Wirksamkeit von molekularem Wasserstoff: Ein neuer mechanistischer Einblick.", "journal": "Current pharmaceutical design", "authors": "Ishibashi", "author_search": "ishibashi ishibashi", "doi": "10.2174/1381612825666190506123038", "doi_url": "https://doi.org/10.2174/1381612825666190506123038", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31057105/", "url": "https://h2medicine.org/studies/study-ishibashi-2019-therapeutic-mechanistic-insight/", "methods": [ "drinking-hrw" ], "indications": [ "neurology", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2019 · Ishibashi — Therapeutic Efficacy of Molecular Hydrogen: A New Mechanistic Insight.", "summary": "Beyond scavenging hydroxyl radicals, molecular hydrogen (H₂) may act directly on mitochondrial complex I — the enzyme that drives cellular energy production. This 2019 review by Ishibashi proposes a novel mechanism: H₂ could donate electrons and protons inside complex I, reducing harmful quinone intermediates and preventing the burst of reactive oxygen species that occurs when oxygen is restored after hypoxia.", "assessment": "This paper offers a creative and testable mechanistic hypothesis about how H₂ interacts with mitochondrial complex I. It moves H₂ research beyond the „simple antioxidant“ framing, which is scientifically valuable. Limitations: this is a theoretical review — the complex-I hypothesis has not yet been experimentally confirmed in mammalian cells or humans in this paper. All cited data are from biochemical analogies and animal physiology. The leap from evolutionary homology (bacterial hydrogenases) to therapeutic action in human disease is speculative at this stage and requires dedicated experimental validation.", "abstract": "BACKGROUND: Molecular hydrogen (H2) is now recognized as a therapeutic gas for the treatment of numerous diseases including neurodegenerative diseases, metabolic disorders, and inflammatory diseases. Nonpolar, neutral H2 is assumed to have health benefits facilitated by its passive diffusion across the human body immediately after administration and is considered a safe therapeutic inert gas that does not interfere with physiological enzymatic reactions. The effects of H2 on mammalian cells are assumed to be based on non-enzymatic reactions with reactive oxygen species (ROS) exhibiting extremely high reactivity. However, many reports on therapeutic applications of H2 have the limitation to regard H2 only as a scavenger for the hydroxyl radical and peroxynitrite. METHODS: Apart from this proposed principle, a new possible mechanism of H2 activation and consumption in mammalian cells is considered in this review, which is specifically focused on the mitochondrial complex I that has a close evolutionary relationship with energy-converting, membrane-bound [NiFe]-hydrogenases (MBH). Notably, the possibility that H2 may function as both electron and proton donor in the ubiquinone-binding chamber of complex I is discussed. RESULTS: H2 is proposed to act as the rectifier of the mitochondrial electron flow in the disordered or pathological state when the accumulation of electrons leads to ROS production, specifically during the re-supply of O2 after hypoxia in the mitochondria. CONCLUSION: Furthermore, H2 is proposed to convert the quinone intermediates to the fully reduced ubiquinol, thereby increasing the antioxidant capacity of the quinone pool as well as preventing the generation of ROS.", "conclusion": "Furthermore, H2 is proposed to convert the quinone intermediates to the fully reduced ubiquinol, thereby increasing the antioxidant capacity of the quinone pool as well as preventing the generation of ROS." }, { "pmid": "30970215", "year": 2019, "title": "Hydrogen gas: from clinical medicine to an emerging ergogenic molecule for sports athletes 1.", "title_en": null, "title_de": "Wasserstoffgas: von der klinischen Medizin zu einem aufkommenden ergogenen Molekül für Sportler.", "journal": "Canadian journal of physiology and pharmacology", "authors": "LeBaron et al.", "author_search": "lebaron le baron", "doi": "10.1139/cjpp-2019-0067", "doi_url": "https://doi.org/10.1139/cjpp-2019-0067", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/30970215/", "url": "https://h2medicine.org/studies/study-lebaron-2019-medicine-emerging-ergogenic-molecule/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "sports-exercise", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2019 · LeBaron et al. — Hydrogen gas: from clinical medicine to an emerging ergogenic molecule for sports athletes.", "summary": "Hydrogen gas (H₂) may serve as both an exercise mimetic and a „redox adaptogen“ — reducing harm from excessive or damaging exercise while potentially amplifying the benefits of healthy training. This 2019 review by LeBaron and colleagues draws parallels between the cellular responses to beneficial exercise and those attributed to H₂, and cautions that more research is needed before strong ergogenic claims can be made.", "assessment": "This is a narrative review that builds a plausible and interesting theoretical framework for H₂ in sports medicine. The „redox adaptogen“ framing is original and well-argued. Limitations: the evidence cited is predominantly preclinical or from early clinical studies; direct ergogenic trials in trained athletes are scarce. The review is co-authored by LeBaron, who has declared interests in the H₂ field. The hypotheses are testable and stimulate future research, but should not be read as established proof of ergogenic benefit.", "abstract": "H2 has been clinically demonstrated to provide antioxidant and anti-inflammatory effects, which makes it an attractive agent in exercise medicine. Although exercise provides a multiplicity of benefits including decreased risk of disease, it can also have detrimental effects. For example, chronic high-intensity exercise in elite athletes, or sporadic bouts of exercise (i.e., noxious exercise) in untrained individuals, result in similar pathological factors such as inflammation, oxidation, and cellular damage that arise from and result in disease. Paradoxically, exercise-induced pro-inflammatory cytokines and reactive oxygen species largely mediate the benefits of exercise. Ingestion of conventional antioxidants and anti-inflammatories often impairs exercise-induced training adaptations. Disease and noxious forms of exercise promote redox dysregulation and chronic inflammation, changes that are mitigated by H2 administration. Beneficial exercise and H2 administration promote cytoprotective hormesis, mitochondrial biogenesis, ATP production, increased NAD+/NADH ratio, cytoprotective phase II enzymes, heat-shock proteins, sirtuins, etc. We review the biomedical effects of exercise and those of H2, and we propose that hydrogen may act as an exercise mimetic and redox adaptogen, potentiate the benefits from beneficial exercise, and reduce the harm from noxious exercise. However, more research is warranted to elucidate the potential ergogenic and therapeutic effects of H2 in exercise medicine.", "conclusion": "We review the biomedical effects of exercise and those of H2, and we propose that hydrogen may act as an exercise mimetic and redox adaptogen, potentiate the benefits from beneficial exercise, and reduce the harm from noxious exercise. However, more research is warranted to elucidate the potential ergogenic and therapeutic effects of H2 in exercise medicine." }, { "pmid": "30773939", "year": 2019, "title": "The preventive and therapeutic effects of molecular hydrogen in ocular diseases and injuries where oxidative stress is involved.", "title_en": null, "title_de": "Die präventiven und therapeutischen Wirkungen von molekularem Wasserstoff bei Augenerkrankungen und -verletzungen, an denen oxidativer Stress beteiligt ist.", "journal": "Free radical research", "authors": "Cejka et al.", "author_search": "cejka cejka", "doi": "10.1080/10715762.2019.1582770", "doi_url": "https://doi.org/10.1080/10715762.2019.1582770", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/30773939/", "url": "https://h2medicine.org/studies/study-cejka-2019-preventive-therapeutic-ocular-diseases/", "methods": [ "unspecified" ], "indications": [ "neurology", "eye", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2019 · Cejka et al. — The preventive and therapeutic effects of molecular hydrogen in ocular diseases and injuries where oxidative stress is involved.", "summary": "Molecular hydrogen (H₂) is uniquely suited for eye diseases because it is the only antioxidant that crosses both the blood-brain and blood-ocular barriers. This 2019 review by Cejka and colleagues surveys preclinical animal studies and some early clinical investigations showing that H₂ treatment suppresses oxidative stress in the eye, helping prevent or improve conditions ranging from glaucoma to age-related macular degeneration.", "assessment": "This is a review of mostly preclinical (animal) research with limited early human data. Its value lies in highlighting H₂'s unique ability to penetrate ocular barriers — a genuine pharmacokinetic advantage not shared by conventional antioxidants. Limitations: the majority of cited evidence comes from animal experiments; extrapolation to human patients requires dedicated clinical trials. The review correctly characterises results as „prevention or improvement“ and „slowing progression“ rather than cures. No clinical toxicity is reported, but administration route for eye conditions (e.g., eye drops, systemic delivery) is not standardised.", "abstract": "Oxidative stress initiates, accompanies and contributes to the development of several human diseases and injuries, including ocular diseases. Reactive oxygen species (ROS) can generate oxidative stress via excessive ROS production and/or decreased physiologically occurring antioxidants. To replace these weakened antioxidants, substances with effective antioxidant properties are needed in order to suppress oxidative stress and enable healing. Molecular hydrogen (H2) is very suitable for this purpose due to its unique properties. H2 is the only antioxidant that crosses the blood-brain and blood-ocular barriers. It quickly penetrates through tissue due to its small molecular size and effectively removes ROS, mainly hydroxyl radicals and peroxynitrite. Apart from its antioxidant effects, H2 also displays anti-inflammatory, antiapoptotic, cytoprotective and mitohormetic properties. A significant advantage of H2 is its nontoxicity, even when applied at high concentrations. In this review, we present the results of studies utilising H2 in the treatment of ocular diseases involving oxidative stress. These results, obtained in experimental animals as well as in human clinical studies, show that the suppression of oxidative stress by H2 treatment leads to the prevention or improvement of ocular diseases. In severe degenerative diseases, H2 slows disease progression.", "conclusion": "These results, obtained in experimental animals as well as in human clinical studies, show that the suppression of oxidative stress by H2 treatment leads to the prevention or improvement of ocular diseases. In severe degenerative diseases, H2 slows disease progression." }, { "pmid": "30543459", "year": 2019, "title": "Molecular hydrogen: potential in mitigating oxidative-stress-induced radiation injury 1.", "title_en": null, "title_de": "Molekularer Wasserstoff: Potenzial zur Minderung von durch oxidativen Stress induzierten Strahlenschäden.", "journal": "Canadian journal of physiology and pharmacology", "authors": "Kura et al.", "author_search": "kura kura", "doi": "10.1139/cjpp-2018-0604", "doi_url": "https://doi.org/10.1139/cjpp-2018-0604", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/30543459/", "url": "https://h2medicine.org/studies/study-kura-2019-mitigating-oxidative-stress-induced/", "methods": [ "unspecified" ], "indications": [ "metabolic", "cardiovascular", "cancer", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2019 · Kura et al. — Molecular hydrogen: potential in mitigating oxidative-stress-induced radiation injury.", "summary": "Molecular hydrogen (H₂) may help protect against radiation-induced oxidative damage by activating the body's own antioxidant defence systems — particularly the Nrf2 pathway — and reducing lipid peroxidation. This 2019 review and proof-of-principle study by Kura and colleagues demonstrates in rats that H₂ administration before irradiation significantly increased protective enzymes (SOD, pAKT) and reduced markers of oxidative damage (lipid peroxidation).", "assessment": "This paper combines a narrative review with a proof-of-principle animal experiment (rat model). The in-vivo data are mechanistically coherent and add value beyond a pure literature review. Limitations: this is animal research — the rat cardiac model cannot be directly extrapolated to human radiation oncology contexts. Dosing, timing, and H₂ concentration used in the animal experiment may differ substantially from what is feasible in clinical practice. Nrf2 pathway activation is a plausible but not yet clinically validated mechanism for H₂'s radioprotective effects. Human trials would be necessary to confirm translational relevance.", "abstract": "Uncontrolled production of oxygen and nitrogen radicals results in oxidative and nitrosative stresses that impair cellular functions and have been regarded as causative common denominators of many pathological processes. In this review, we report on the beneficial effects of molecular hydrogen in scavenging radicals in an artificial system of •OH formation. As a proof of principle, we also demonstrate that in rat hearts in vivo, administration of molecular hydrogen led to a significant increase in superoxide dismutase as well as pAKT, a cell survival signaling molecule. Irradiation of the rats caused a significant increase in lipid peroxidation, which was mitigated by pre-treatment of the animals with molecular hydrogen. The nuclear factor erythroid 2-related factor 2 is regarded as an important regulator of oxyradical homeostasis, as well as it supports the functional integrity of cells, particularly under conditions of oxidative stress. We suggest that the beneficial effects of molecular hydrogen may be through the activation of nuclear factor erythroid 2-related factor 2 pathway that promotes innate antioxidants and reduction of apoptosis, as well as inflammation.", "conclusion": "The nuclear factor erythroid 2-related factor 2 is regarded as an important regulator of oxyradical homeostasis, as well as it supports the functional integrity of cells, particularly under conditions of oxidative stress. We suggest that the beneficial effects of molecular hydrogen may be through the activation of nuclear factor erythroid 2-related factor 2 pathway that promotes innate antioxidant" }, { "pmid": "30529801", "year": 2019, "title": "Hydrogen as a complementary therapy against ischemic stroke: A review of the evidence.", "title_en": null, "title_de": "Wasserstoff als komplementäre Therapie gegen den ischämischen Schlaganfall: Eine Übersicht über die Evidenz.", "journal": "Journal of the neurological sciences", "authors": "Li et al.", "author_search": "li li", "doi": "10.1016/j.jns.2018.11.004", "doi_url": "https://doi.org/10.1016/j.jns.2018.11.004", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/30529801/", "url": "https://h2medicine.org/studies/study-li-2019-complementary-against-ischemic-stroke/", "methods": [ "inhalation" ], "indications": [ "neurology", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2019 · Li et al. — Hydrogen as a complementary therapy against ischemic stroke: A review of the evidence.", "summary": "Hydrogen gas inhalation has been studied as a complementary treatment for ischemic stroke, targeting the damaging cascade of free radicals and inflammation that unfolds after a blood vessel in the brain is blocked. This 2019 review by Li and colleagues surveys experimental and clinical trial data, finding that H₂ therapy shows anti-oxidative, anti-inflammatory, and anti-apoptotic effects relevant to stroke recovery.", "assessment": "This is a literature review covering both animal experiments and clinical trial data on H₂ for ischemic stroke. The honest framing — „complementary therapy“, „future investigations“ — reflects the still-emerging nature of the clinical evidence. Limitations: the number of controlled clinical trials in stroke is small; animal models of stroke often overestimate efficacy translatable to humans; delivery logistics for H₂ inhalation in acute stroke settings are complex. The review does not pool effect sizes and cannot establish efficacy. It should be read as a synthesis of promising early signals requiring larger, well-designed trials.", "abstract": "Ischemic stroke is one of the most common sources of mortality in the world. Researchers have been trying to find a complementary therapy to treat ischemic stroke in order to improve its prognosis and expand the therapeutic window for reperfusion treatment. For this reason, many experimental and clinical trials studying the effects of hydrogen against ischemic stroke have been published. Hydrogen gas has been found to eliminate hydroxyl free radical and peroxynitrite anions as well as producing therapeutic effect in patients with ischemic stroke. Many studies have been published illustrating its anti-oxidative, anti-inflammatory and anti-apoptotic effects. The purpose of this article is to review the literature concerning treatment of cerebral I/R injury or ischemic stroke with hydrogen therapy. Specifically, we will examine the appropriate laboratory methods, mechanisms of hydrogen therapy, and outcomes of relevant clinical trials. We conclude this review with a discussion on future investigations of hydrogen therapy to treat ischemic stroke.", "conclusion": "Specifically, we will examine the appropriate laboratory methods, mechanisms of hydrogen therapy, and outcomes of relevant clinical trials. We conclude this review with a discussion on future investigations of hydrogen therapy to treat ischemic stroke." }, { "pmid": "29681183", "year": 2019, "title": "Neonatal hypoxic-ischemic encephalopathy: emerging therapeutic strategies based on pathophysiologic phases of the injury.", "title_en": null, "title_de": "Neonatale hypoxisch-ischämische Enzephalopathie: aufkommende therapeutische Strategien auf Basis der pathophysiologischen Phasen der Schädigung.", "journal": "The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians", "authors": "Wang et al.", "author_search": "wang wang", "doi": "10.1080/14767058.2018.1468881", "doi_url": "https://doi.org/10.1080/14767058.2018.1468881", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/29681183/", "url": "https://h2medicine.org/studies/study-wang-2019-neonatal-hypoxic-ischemic-encephalopathy/", "methods": [ "saline-iv" ], "indications": [ "sports-exercise", "neurology", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2019 · Wang et al. — Neonatal hypoxic-ischemic encephalopathy: emerging therapeutic strategies based on pathophysiologic phases of the injury.", "summary": "This 2019 review proposes a phase-based treatment framework for neonatal hypoxic-ischemic encephalopathy (HIE), a major cause of infant death and disability. Hydrogen-rich saline appears alongside other neuroprotective agents as a candidate free-radical scavenger in the earliest injury phase, potentially complementing standard mild hypothermia therapy.", "assessment": "This is a broad narrative review of emerging treatments for neonatal HIE — hydrogen-rich saline is one of many agents mentioned, not the paper's primary focus. The evidence for H₂ in this neonatal context is preclinical; no neonatal clinical trial data for H₂ are presented. The phase-based treatment framework is conceptually useful. Limitations: the paper is primarily a framework proposal rather than a systematic evidence review; H₂ evidence for neonatal HIE specifically is sparse in 2019; extrapolation from adult or animal models to critically ill newborns is especially hazardous.", "abstract": "Neonatal hypoxic ischemic encephalopathy (HIE) is an important cause of neonatal death and disability. At present, there is no unified standard and specialized treatment method for neonatal HIE. In clinical practice, we have found that a gap remains between preclinical medical research and clinical application in the treatment of neonatal HIE. To promote an organic combination of preclinical research and clinical application, we propose the different phases as intervention targets, based on the pathophysiologic changes in phases I, II, and III of neonatal HIE; moreover, we suggest transformative medicine as a principle that may improve the therapeutic effect by blocking the progression of the disease to an irreversible stage. For instance, in phase I, mild hypothermia, free radical scavenger (erythropoietin, hydrogen-rich saline), excitatory amino acid receptor blocker, and neuroprotective agents should be administered to neonates with moderate/severe HIE; in phase II, following phase I treatment, anti-inflammatory agents, neuroprotective or nerve regeneration agents, and stem cell transplantation should be administered to patients; in phase III, anti-inflammatory agents, neuroprotective or nerve regeneration agents, and stem cell transplantation should be administered to patients. As soon as the patient's condition has stabilized, acupuncture, massage, and rehabilitation training should be performed. Following further study of stem cells, stem cell transplantation is expected to become the most promising therapeutic candidate for treatment of severe neonatal HIE with its sequelae.", "conclusion": "As soon as the patient's condition has stabilized, acupuncture, massage, and rehabilitation training should be performed. Following further study of stem cells, stem cell transplantation is expected to become the most promising therapeutic candidate for treatment of severe neonatal HIE with its sequelae." }, { "pmid": "31251888", "year": 2019, "title": "Drinking hydrogen water enhances endurance and relieves psychometric fatigue: a randomized, double-blind, placebo-controlled study", "title_en": null, "title_de": "Trinken von Wasserstoffwasser steigert die Ausdauer und lindert psychometrische Ermüdung: eine randomisierte, doppelblinde, placebo-kontrollierte Studie", "journal": "Canadian Journal of Physiology and Pharmacology", "authors": "Mikami et al.", "author_search": "mikami mikami", "doi": "10.1139/cjpp-2019-0059", "doi_url": "https://doi.org/10.1139/cjpp-2019-0059", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31251888/", "url": "https://h2medicine.org/studies/study-mikami-2019-endurance-psychometric-fatigue/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise", "oxidative-stress" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2019 · Mikami — Drinking hydrogen water enhances endurance and relieves psychometric fatigue: a randomized, double-blind, placebo-controlled study", "summary": "Hydrogen water shortly before exercise lowered the sensation of fatigue and increased endurance. In two randomized, double-blind, placebo-controlled experiments (n = 99 untrained; n = 60 trained), subjective fatigue, maximal oxygen consumption and the Borg scale improved. (Can J Physiol Pharmacol, 2019.)", "assessment": "A comparatively large, doubled RCT (159 participants in total) with two separate experiments — making the finding more robust than many mini-studies in the sports field. Especially valuable as an educational argument is the observation that more fatigued people benefit more — consistent with the idea that H₂ works mainly where oxidative stress is high. A co-author is Tyler W. LeBaron (Molecular Hydrogen Institute), alongside Shigeo Ohta — this strengthens subject-matter proximity but must also be noted as a possible conflict of interest. Limitations, stated honestly: some of the endpoints are subjective (fatigue scales, Borg), which are susceptible to expectancy effects, even though the design is double-blind and placebo-controlled. In the overall picture this positive finding stands alongside honest null results of other sports studies — dose, training status and exercise type seem to be co-decisive.", "abstract": "Acute physical exercise increases reactive oxygen species in skeletal muscle, leading to tissue damage and fatigue. Molecular hydrogen (H2) acts as a therapeutic antioxidant directly or indirectly by inducing antioxidative enzymes. Here, we examined the effects of drinking H2 water (H2-infused water) on psychometric fatigue and endurance capacity in a randomized, double-blind, placebo-controlled fashion. In Experiment 1, all participants drank only placebo water in the first cycle ergometer exercise session, and for comparison they drank either H2 water or placebo water 30 min before exercise in the second examination. In these healthy non-trained participants (n = 99), psychometric fatigue judged by visual analogue scales was significantly decreased in the H2 group after mild exercise. When each group was divided into 2 subgroups, the subgroup with higher visual analogue scale values was more sensitive to the effect of H2. In Experiment 2, trained participants (n = 60) were subjected to moderate exercise by cycle ergometer in a similar way as in Experiment 1, but exercise was performed 10 min after drinking H2 water. Endurance and fatigue were significantly improved in the H2 group as judged by maximal oxygen consumption and Borg's scale, respectively. Taken together, drinking H2 water just before exercise exhibited anti-fatigue and endurance effects.", "conclusion": "Endurance and fatigue were significantly improved in the H2 group as judged by maximal oxygen consumption and Borg's scale, respectively. Taken together, drinking H2 water just before exercise exhibited anti-fatigue and endurance effects." }, { "pmid": "31574544", "year": 2019, "title": "Hydrogen Rich Water Improved Ventilatory, Perceptual and Lactate Responses to Exercise", "title_en": null, "title_de": "Wasserstoffreiches Wasser verbesserte ventilatorische, perzeptuelle und Laktat-Reaktionen auf Belastung", "journal": "International Journal of Sports Medicine", "authors": "Botek et al.", "author_search": "botek botek", "doi": "10.1055/a-0991-0268", "doi_url": "https://doi.org/10.1055/a-0991-0268", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31574544/", "url": "https://h2medicine.org/studies/study-botek-2019-ventilatory-lactate-responses-exercise/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2019 · Botek — Hydrogen Rich Water Improved Ventilatory, Perceptual and Lactate Responses to Exercise", "summary": "600 ml of hydrogen water before exercise lowered the lactate level at high intensities and improved breathing efficiency and perception of effort. Randomized, double-blind, placebo-controlled crossover study with 12 healthy men. (Int J Sports Med, 2019.)", "assessment": "A methodologically solid double-blind, placebo-controlled crossover RCT with a positive result — and a good counterweight to null findings of other sports studies. The decisive difference likely lies in the dose (600 ml here vs. 2 × 290 ml there) and in the exercise type. Notable as evidence that H₂ water during intense endurance exercise can show measurable physiological effects (lower lactate, better breathing efficiency) given a sufficient amount. Limitations, stated honestly: very small sample (n = 12), exclusively healthy men, an acute single dose (no statement on long-term benefit), and the endpoints are physiological surrogate markers plus subjective RPE — no direct proof of competition performance.", "abstract": "The potential anti-fatigue and performance benefits of hydrogen rich water (HRW) have resulted in increased research interest over the past 5 years. The aim of this study was to assess physiological and perceptual responses to an incremental exercise protocol after administration of 600 ml HRW within 30 min before exercise. This randomized, double blinded placebo-controlled cross over study included twelve healthy males aged 27.1±4.9 years. The exercise protocol consisted of a 10 min warm-up at 1.0 W.kg-1, followed by 8 min at 2.0, 3.0, and 4.0 W.kg-1, respectively. Cardio-respiratory variables, lactate and ratings of perceived exertion (RPE) were assessed in the last minute of each step. A significantly lower blood lactate was found with HRW (4.0±1.6 and 8.9±2.2 mmol.l-1) compared to Placebo (5.1±1.9 and 10.6±3.0 mmol.l-1) at 3.0, and 4.0 W.kg-1, respectively. Ventilatory equivalent for oxygen and RPE exhibited significantly lower values with HRW (32.3±7.2, and 17.8±1.2 points, respectively) compared to Placebo (35.0±8.4, and 18.5±0.8 points, respectively) at 4 W.kg-1. To conclude, acute pre-exercise supplementation with HRW reduced blood lactate at higher exercise intensities, improved exercise-induced perception of effort, and ventilatory efficiency.", "conclusion": "Ventilatory equivalent for oxygen and RPE exhibited significantly lower values with HRW (32.3±7.2, and 17.8±1.2 points, respectively) compared to Placebo (35.0±8.4, and 18.5±0.8 points, respectively) at 4 W.kg-1. To conclude, acute pre-exercise supplementation with HRW reduced blood lactate at higher exercise intensities, improved exercise-induced perception of effort, and ventilatory efficiency." }, { "pmid": "30982748", "year": 2019, "title": "Hydrogen-rich water reduces liver fat accumulation and improves liver enzyme profiles in patients with non-alcoholic fatty liver disease: a randomized controlled pilot trial.", "title_en": null, "title_de": "Wasserstoffreiches Wasser reduziert die Fettansammlung in der Leber und verbessert die Leberenzymprofile bei Patienten mit nicht-alkoholischer Fettlebererkrankung: eine randomisierte kontrollierte Pilotstudie.", "journal": "Clinics and research in hepatology and gastroenterology", "authors": "Korovljev et al.", "author_search": "korovljev korovljev", "doi": "10.1016/j.clinre.2019.03.008", "doi_url": "https://doi.org/10.1016/j.clinre.2019.03.008", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/30982748/", "url": "https://h2medicine.org/studies/study-korovljev-2019-reduces-liver-fat-accumulation/", "methods": [ "drinking-hrw" ], "indications": [ "metabolic", "liver", "fundamentals-safety" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2019 · Korovljev et al. — Hydrogen-rich water reduces liver fat accumulation and improves liver enzyme profiles in patients with non-alcoholic fatty liver disease: a randomized controlled pilot trial.", "summary": "In a double-blind crossover trial with 12 overweight NAFLD patients, 28 days of 1 L/day hydrogen-rich water significantly reduced liver fat measured by MRI (from 284 to 256.5 mM, –2.9 %) and tended to lower aspartate transaminase by 10 %, compared to placebo. Body weight and body composition were not significantly altered. The authors carefully frame this as a preliminary pilot warranting follow-up trials. (Clinics and Research in Hepatology and Gastroenterology, 2019.)", "assessment": "This is a carefully conducted small pilot with a clinically meaningful endpoint (MRI liver fat). The double-blind crossover design with an objective primary outcome is a significant methodological strength. Limitations: n = 12 — severely underpowered for definitive conclusions; crossover design in a chronic disease (NAFLD) carries carryover risk even with washout; the AST reduction did not reach significance; no liver biopsy (histology); no long-term follow-up. The study is an appropriate basis for a larger randomised trial — it cannot stand alone as evidence of benefit.", "abstract": "BACKGROUND AND AIMS: While non-alcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disease worldwide, its treatment remains elusive. Since metabolic impairment plays a major role in NAFLD pathogenesis, any pharmaceuticals, such as molecular hydrogen (H2), that advance lipid and glucose metabolism could be appropriate to tackle this complex condition. The aim of this study was to analyze the effects of 28-day hydrogen-rich water intake on liver fat deposition, body composition and lab chemistry profiles in overweight patients suffering from mild-to-moderate NAFLD. METHODS: Twelve overweight outpatients with NAFLD (age 56.2 ± 10.0 years; body mass index 37.7 ± 5.3 kg/m2; 7 women and 5 men) voluntarily participated in this double-blind, placebo-controlled, crossover trial. All patients were allocated to receive either 1 L per day of hydrogen-rich water (HRW) or placebo water for 28 days. The study was registered at ClinicalTrials.gov (ID NCT03625362). RESULTS: Dual-echo MRI revealed that HRW significantly reduced liver fat accumulation in individual liver regions-of-interest at 28-day follow-up, as compared to placebo administration (P < 0.05). Baseline liver fat content was reduced from 284.0 ± 118.1 mM to 256.5 ± 108.3 mM after hydrogen treatment at 28-day follow-up (percent change 2.9%; 95% CI from 0.5 to 5.5). Serum aspartate transaminase levels dropped by 10.0% (95% CI; from -23.2 to 3.4) after hydrogen treatment at 28-day follow-up. No significant differences were observed between treatment groups in either weight or body composition among participants. CONCLUSIONS: Although preliminary, the results of this trial perhaps nominate HRW as an adjuvant treatment for mild-to-moderate NAFLD. These observations provide a rationale for further clinical trials to establish safety and efficacy of molecular hydrogen in NAFLD.", "conclusion": "Although preliminary, the results of this trial perhaps nominate HRW as an adjuvant treatment for mild-to-moderate NAFLD. These observations provide a rationale for further clinical trials to establish safety and efficacy of molecular hydrogen in NAFLD." }, { "pmid": "30542740", "year": 2019, "title": "Hydrogen gas restores exhausted CD8+ T cells in patients with advanced colorectal cancer to improve prognosis.", "title_en": null, "title_de": "Wasserstoffgas stellt erschöpfte CD8+-T-Zellen bei Patienten mit fortgeschrittenem kolorektalem Karzinom wieder her und verbessert so die Prognose.", "journal": "Oncology reports", "authors": "Akagi et al.", "author_search": "akagi akagi", "doi": "10.3892/or.2018.6841", "doi_url": "https://doi.org/10.3892/or.2018.6841", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/30542740/", "url": "https://h2medicine.org/studies/study-akagi-2019-restores-exhausted-cd8-cells/", "methods": [ "inhalation" ], "indications": [ "cancer" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2019 · Akagi et al. — Hydrogen gas restores exhausted CD8+ T cells in patients with advanced colorectal cancer to improve prognosis.", "summary": "In 55 stage IV colorectal cancer patients inhaling H₂ gas (3 h/day at home) alongside chemotherapy, H₂ was associated with a shift in exhausted CD8+ T cells: fewer terminal PD-1+ exhausted cells, more active PD-1− cells — and both progression-free and overall survival were better in patients with the more favourable T-cell balance. This observational study proposes a novel patient classification system based on the PD-1+/PD-1− CD8 T-cell ratio. (Oncology Reports, 2019.)", "assessment": "A mechanistically rich observational study that connects H₂ biology (PGC-1α, mitochondrial function) to immune oncology (CD8 T-cell exhaustion) in a real cancer patient population. The PD-1+/PD-1− T-cell ratio as a prognostic index is novel and clinically potentially valuable. Limitations: all patients received H₂ — no untreated comparison arm for survival outcomes; chemotherapy confounds T-cell dynamics; n = 55 is relatively small for survival analysis in a heterogeneous metastatic cohort; home-based inhalation adherence not quantified; the PGC-1α mechanism in human patients is inferred, not directly measured.", "abstract": "Exhausted cluster of differentiation (CD)8+ T cells lose immunological activity due to mitochondrial dysfunction caused by peroxisome proliferator‑activated receptor γ coactivator 1α (PGC‑1α) inactivation, resulting in a poor prognosis in patients with cancer. As hydrogen gas was recently reported to activate PGC‑1α, the present study investigated whether it restores exhausted CD8+ T cells to improve prognosis in patients with stage IV colorectal cancer. A total of 55 patients with histologically and clinically diagnosed stage IV colorectal carcinoma were enrolled between July 2014 and July 2017. The patients inhaled hydrogen gas for 3 h/day at their own homes and received chemotherapy at the Tamana Regional Health Medical Center (Tamana, Kumamoto, Japan). The CD8+ T cells were isolated from the peripheral blood and their phenotype was analyzed by flow cytometry. It was found that exhausted terminal programmed cell death 1 (PD‑1)+ CD8+ T cells in the peripheral blood are independently associated with worse progression‑free survival (PFS) and overall survival (OS). Notably, hydrogen gas decreased the abundance of exhausted terminal PD‑1+ CD8+ T cells, increased that of active terminal PD‑1‑ CD8+ T cells, and improved PFS and OS times, suggesting that the balance between terminal PD1+ and PD1‑ CD8+ T cells is critical for cancer prognosis. Therefore, a novel system for patient classification (category 1‑4) was developed in the present study based on these two indices to assist in predicting the prognosis and therapeutic response. Collectively, the present results suggested that hydrogen gas reverses imbalances toward PD‑1+ CD8+ T cells to provide an improved prognosis.", "conclusion": "Therefore, a novel system for patient classification (category 1‑4) was developed in the present study based on these two indices to assist in predicting the prognosis and therapeutic response. Collectively, the present results suggested that hydrogen gas reverses imbalances toward PD‑1+ CD8+ T cells to provide an improved prognosis." }, { "pmid": "32595937", "year": 2019, "title": "Case Report: Buccal administration of hydrogen-producing blend after a mild traumatic brain injury in a professional athlete.", "title_en": null, "title_de": "Fallbericht: Bukkale Verabreichung einer wasserstoffproduzierenden Mischung nach einem leichten Schädel-Hirn-Trauma bei einem professionellen Athleten.", "journal": "F1000Research", "authors": "Javorac et al.", "author_search": "javorac javorac", "doi": "10.12688/f1000research.19739.1", "doi_url": "https://doi.org/10.12688/f1000research.19739.1", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32595937/", "url": "https://h2medicine.org/studies/study-javorac-2019-buccal-administration-producing-blend/", "methods": [ "tablets", "drinking-hrw" ], "indications": [ "sports-exercise", "neurology", "fundamentals-safety" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2019 · Javorac et al. — Case Report: Buccal administration of hydrogen-producing blend after a mild traumatic brain injury in a professional athlete.", "summary": "A professional soccer player with a mild sport-related traumatic brain injury (TBI) received a hydrogen-producing dissolving tablet buccally every 2 hours for 24 hours post-injury, starting ~15 minutes after the event; the SCAT2 concussion assessment score improved from 68 (severe disruption) to 84 (mild disruption) at 24-hour follow-up, and no side effects were reported. This is a single-case report — it establishes feasibility and safety in one individual but cannot determine whether H₂ drove the recovery. (F1000Research, 2019.)", "assessment": "The report provides a well-documented intervention protocol for buccal H₂ delivery post-concussion and confirms tolerability in one patient. The authors overstate conclusions slightly (using „beneficial strategy“ for a single uncontrolled case), though the clinical rationale — H₂ as neuroprotective in early TBI — has preclinical support. Limitations: n = 1; no control; rapid SCAT2 improvement is expected in mild TBI regardless of intervention; H₂ release kinetics from the buccal tablet not characterised; SCAT2 is self-reported in part. This is hypothesis-generating only.", "abstract": "Background: Sport-related mild traumatic brain injury (TBI) is a serious trauma that could impair brain function of an injured athlete. Treatment solutions for mild TBI typically concentrate on complete rest, while non-traditional therapeutic options remain largely ineffective. Molecular hydrogen (H 2 ) is an innovative neuroprotective agent that can easily reach the brain, yet no data are available concerning its value as a first-aid intervention after a mild TBI. Case report: This case report demonstrates the efficacy and safety of a hydrogen-producing dissolving tablet administered buccally during the first 24 hours post-injury in a professional soccer player who suffered a mild TBI. The patient received a formulated dosage of hydrogen every 2 hours, with the first intervention given immediately after an initial examination (~ 15 min after the injury). The overall score for Sport Concussion Assessment Tool 2 (SCAT2), a standardized method of evaluating injured athletes for concussion, increased from 68 points (severe disruption) at baseline to 84 points (mild disruption) at 24-h follow-up. The patient reported no side effects of hydrogen intervention. Conclusions: This case has demonstrated that intensive consecutive therapy with oral transmucosal hydrogen formulation is a beneficial strategy with regard to the reduction of presence and severity of symptoms of sport-related mild TBI.", "conclusion": "This case has demonstrated that intensive consecutive therapy with oral transmucosal hydrogen formulation is a beneficial strategy with regard to the reduction of presence and severity of symptoms of sport-related mild TBI." }, { "pmid": "32255077", "year": 2019, "title": "Acid-responsive H2-releasing Fe nanoparticles for safe and effective cancer therapy.", "title_en": null, "title_de": "Säureempfindliche, H₂-freisetzende Fe-Nanopartikel für eine sichere und wirksame Krebstherapie.", "journal": "Journal of materials chemistry. B", "authors": "Kou et al.", "author_search": "kou kou", "doi": "10.1039/c9tb00338j", "doi_url": "https://doi.org/10.1039/c9tb00338j", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/32255077/", "url": "https://h2medicine.org/studies/study-kou-2019-acid-responsive-releasing-nanoparticles/", "methods": [ "saline-iv" ], "indications": [ "liver", "sports-exercise", "cancer", "skin-aging", "immune-system", "fundamentals-safety" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2019 · Kou et al. — Acid-responsive H₂-releasing Fe nanoparticles for safe and effective cancer therapy.", "summary": "This preclinical study describes an ingenious drug-delivery strategy: iron nanoparticles coated with carboxymethyl cellulose that release molecular hydrogen (H₂) selectively inside the acidic tumour microenvironment, enabling targeted, imaging-guided cancer therapy in mice. The Fe@CMC nanoparticles showed high tumour accumulation, strong cancer-cell-killing selectivity, and no observable toxicity in healthy tissue — all in animal and cell experiments.", "assessment": "This is a preclinical study (cell culture + mouse tumour model) with no human data. It demonstrates a creative and technically sophisticated H₂ delivery strategy. Important caveat: mouse tumour models often fail to predict clinical outcomes in human oncology; nanomedicine candidates face major hurdles in scale-up, safety profiling, regulatory approval, and clinical translation. The energy-metabolism disruption mechanism is novel but needs independent replication. This should be read as an innovative proof-of-concept, not as evidence of cancer therapy in humans.", "abstract": "Hydrogen therapy is an emerging and promising strategy for treatment of inflammation-related diseases owing to the excellent bio-safety of hydrogen molecules (H2), but is facing a challenge that the H2 concentration at the local disease site is hardly accumulated because of its high diffusibility and low solubility, limiting the efficacy of hydrogen therapy. Herein, we propose a nanomedicine strategy of imaging-guided tumour-targeted delivery and tumour microenvironment-triggered release of H2 to address this issue, and develop a kind of biocompatible carboxymethyl cellulose (CMC)-coated/stabilized Fe (Fe@CMC) nanoparticle with photoacoustic imaging (PAI), tumour targeting and acid responsive hydrogen release properties for cancer therapy. The Fe@CMC nanoparticles have demonstrated high intratumoural accumulation capability, high acid responsiveness, excellent PAI performance, selective cancer-killing effect and high bio-safety in vitro and in vivo. Effective inhibition of tumour growth is achieved by intravenous injection of the Fe@CMC nanoparticles, and the selective anti-cancer mechanism of Fe@CMC is discovered to be originated from the energy metabolism homeostasis regulatory function of the released H2. The proposed nanomedicine-mediated hydrogen therapy strategy will open a new window for precise, high-efficacy and safe cancer treatment.", "conclusion": "Effective inhibition of tumour growth is achieved by intravenous injection of the Fe@CMC nanoparticles, and the selective anti-cancer mechanism of Fe@CMC is discovered to be originated from the energy metabolism homeostasis regulatory function of the released H2. The proposed nanomedicine-mediated hydrogen therapy strategy will open a new window for precise, high-efficacy and safe cancer treatment" }, { "pmid": "31768722", "year": 2019, "title": "Effect of hydrogen-rich water on the Nrf2/ARE signaling pathway in rats with myocardial ischemia-reperfusion injury.", "title_en": null, "title_de": "Wirkung von wasserstoffreichem Wasser auf den Nrf2/ARE-Signalweg bei Ratten mit myokardialem Ischämie-Reperfusionsschaden.", "journal": "Journal of bioenergetics and biomembranes", "authors": "Li et al.", "author_search": "li li", "doi": "10.1007/s10863-019-09814-7", "doi_url": "https://doi.org/10.1007/s10863-019-09814-7", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31768722/", "url": "https://h2medicine.org/studies/study-li-2019-nrf2-signaling-pathway-rats/", "methods": [ "drinking-hrw" ], "indications": [ "cardiovascular", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2019 · Li et al. — Effect of hydrogen-rich water on the Nrf2/ARE signaling pathway in rats with myocardial ischemia-reperfusion injury.", "summary": "In isolated rat hearts, drinking hydrogen-rich water before and during ischemia-reperfusion dramatically boosted the heart's own antioxidant defences — activating the Nrf2/ARE signalling pathway, increasing protective enzymes (NQO1, HO-1, SOD-1), and reducing oxidative damage (MDA). This is a preclinical animal study; the results do not yet constitute evidence for human heart disease.", "assessment": "This is a well-designed preclinical animal study (rat ex-vivo model) with detailed molecular endpoint analysis. It provides mechanistic support for H₂ acting via the Nrf2/ARE pathway in cardiac ischemia-reperfusion. Limitations: the Langendorff perfusion model is an isolated ex-vivo system that does not replicate the complexity of a living animal or human patient; the study uses drinking-water pre-treatment in animals, which may not correspond to achievable H₂ concentrations or timing in human clinical settings; results cannot be directly extrapolated to human myocardial infarction or cardiac surgery.", "abstract": "The effects of hydrogen-rich water on oxidative stress via the Nrf2/ARE signaling pathway were studied in rats with myocardial ischemia-reperfusion injury (MIRI). Sixty rats were randomly divided into a hydrogen-rich water group and a control group, with 30 rats in each group. The two groups were randomly divided into three groups: pre-ischemic period, ischemic period and reperfusion period. After the heart was removed, it was fixed in a Langendorff device and perfused with an oxygen-balanced 37 °C perfusate. The control group was perfused with Kreb's-Ringers (K-R) solution, and the hydrogen-rich water group was perfused with K-R solution + hydrogen-rich water. The levels of mRNA and protein of Nrf2, NQO1, HO-1 and SOD-1 in cardiomyocytes were detected by RT-qPCR, immunohistochemistry (IHC) and Western blot analysis. SOD activity and MDA content were determined. Hydrogen-rich water increased the activation of the Nrf2/ARE signaling pathway, and the levels of mRNA and protein Nrf2, NQO1, HO-1 and SOD-1 were significantly increased (P < 0.05) in the ischemia-reperfusion period compared with the ischemic period. In the control group, the levels of mRNA and protein of Nrf2, NQO1, HO-1 and SOD-1 were significantly decreased (P < 0.05) in the ischemia-reperfusion period compared with the ischemic period. Compared with the ischemic period, the ischemia-reperfusion phase showed significantly increased SOD activity and significantly decreased MDA content in the hydrogen-rich water group, while SOD activity was significantly decreased, and MDA content was significantly increased in the control group (P < 0.05). Hydrogen-rich water can activate the Nrf2/ARE signaling pathway, alleviate ischemia-reperfusion injury in isolated rat hearts and reduce the oxidative stress level of myocardial tissue.", "conclusion": "Compared with the ischemic period, the ischemia-reperfusion phase showed significantly increased SOD activity and significantly decreased MDA content in the hydrogen-rich water group, while SOD activity was significantly decreased, and MDA content was significantly increased in the control group (P < 0.05). Hydrogen-rich water can activate the Nrf2/ARE signaling pathway, alleviate ischemia-reperfu" }, { "pmid": "31738389", "year": 2019, "title": "Molecular hydrogen: current knowledge on mechanism in alleviating free radical damage and diseases.", "title_en": null, "title_de": "Molekularer Wasserstoff: aktueller Kenntnisstand zum Mechanismus bei der Linderung von Schäden durch freie Radikale und von Erkrankungen.", "journal": "Acta biochimica et biophysica Sinica", "authors": "Tao et al.", "author_search": "tao tao", "doi": "10.1093/abbs/gmz121", "doi_url": "https://doi.org/10.1093/abbs/gmz121", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31738389/", "url": "https://h2medicine.org/studies/study-tao-2019-current-knowledge-mechanism-alleviating/", "methods": [ "unspecified" ], "indications": [ "metabolic", "cancer", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2019 · Tao et al. — Molecular hydrogen: current knowledge on mechanism in alleviating free radical damage and diseases.", "summary": "Since molecular hydrogen was identified as a hydroxyl radical scavenger in 2007, beneficial effects have been documented in over 170 disease models and human conditions. This 2019 review by Tao and colleagues systematically maps the current mechanistic understanding of how H₂ exerts its antioxidative, anti-inflammatory, and anti-apoptotic effects — including its protection of mitochondria, the endoplasmic reticulum, and its regulation of intracellular signalling and immune cell balance.", "assessment": "This is a comprehensive mechanistic review that provides a well-organised map of the current H₂ research landscape as of 2019. Its honest acknowledgement of mechanistic uncertainty is commendable. Limitations: it is a narrative review and cannot establish clinical efficacy; the enormous breadth (170+ disease models) risks superficiality on any single topic; much of the cited mechanistic data comes from cell and animal studies. The review is a useful orientation document for researchers but cannot be cited as clinical proof of H₂'s benefits in specific human diseases.", "abstract": "Ever since molecular hydrogen was first reported as a hydroxyl radical scavenger in 2007, the beneficial effect of hydrogen was documented in more than 170 disease models and human diseases including ischemia/reperfusion injury, metabolic syndrome, inflammation, and cancer. All these pathological damages are concomitant with overproduction of reactive oxygen species (ROS) where molecular hydrogen has been widely demonstrated as a selective antioxidant. Although it is difficult to construe the molecular mechanism of hydrogen's biomedical effect, an increasing number of studies have been helping us draw the picture clearer with days passing by. In this review, we summarized the current knowledge on systemic and cellular modulation by hydrogen treatment. We discussed the antioxidative, anti-inflammatory, and anti-apoptosis effects of hydrogen, as well as its protection on mitochondria and the endoplasmic reticulum, regulation of intracellular signaling pathways, and balancing of the immune cell subtypes. We hope that this review will provide organized information that prompts further investigation for in-depth studies of hydrogen effect.", "conclusion": "We discussed the antioxidative, anti-inflammatory, and anti-apoptosis effects of hydrogen, as well as its protection on mitochondria and the endoplasmic reticulum, regulation of intracellular signaling pathways, and balancing of the immune cell subtypes. We hope that this review will provide organized information that prompts further investigation for in-depth studies of hydrogen effect." }, { "pmid": "31737671", "year": 2019, "title": "Inhaling Hydrogen Ameliorates Early Postresuscitation EEG Characteristics in an Asphyxial Cardiac Arrest Rat Model.", "title_en": null, "title_de": "Die Inhalation von Wasserstoff verbessert frühe EEG-Charakteristika nach der Reanimation in einem Modell des asphyktischen Herzstillstands bei Ratten.", "journal": "BioMed research international", "authors": "Chen et al.", "author_search": "chen chen", "doi": "10.1155/2019/6410159", "doi_url": "https://doi.org/10.1155/2019/6410159", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31737671/", "url": "https://h2medicine.org/studies/study-chen-2019-inhaling-ameliorates-early-postresuscitation/", "methods": [ "inhalation" ], "indications": [ "sports-exercise", "neurology", "cardiovascular", "respiratory" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2019 · Chen et al. — Inhaling Hydrogen Ameliorates Early Postresuscitation EEG Characteristics in an Asphyxial Cardiac Arrest Rat Model.", "summary": "In a rat model of asphyxial cardiac arrest, breathing 2% hydrogen gas after resuscitation dramatically improved both survival (90% vs. 40%) and the recovery of brain electrical activity (EEG) within four hours. EEG characteristics in the hydrogen-treated animals correlated with better neurological outcomes at 96 hours — but this is an animal study and does not directly translate to human cardiopulmonary resuscitation.", "assessment": "This is a well-controlled preclinical animal study (rat asphyxial cardiac arrest model) with impressive results that raise genuine scientific interest. Limitations: rat physiology and cardiac arrest models differ substantially from human cardiopulmonary resuscitation; 40 animals is a small sample; the study was conducted under normothermia, whereas clinical post-resuscitation care often includes targeted temperature management that may interact with H₂; the EEG analysis methods need validation in human settings. The results are hypothesis-generating and support further clinical research, but cannot be directly applied to human post-cardiac-arrest care.", "abstract": "BACKGROUND: Electroencephalography (EEG) is commonly used to assess the neurological prognosis of comatose patients after cardiac arrest (CA). However, the early prognostic accuracy of EEG may be affected by postresuscitation interventions. Recent animal studies found that hydrogen inhalation after CA greatly improved neurological outcomes by selectively neutralizing highly reactive oxidants, but the effect of hydrogen inhalation on EEG recovery and its prognostication value are still unclear. The present study investigated the effects of hydrogen inhalation on early postresuscitation EEG characteristics in an asphyxial CA rat model. METHODS: Cardiopulmonary resuscitation was initiated after 5 min of untreated CA in 40 adult female Sprague-Dawley rats. Animals were randomized for ventilation with 98% oxygen plus 2% hydrogen (H2) or 98% oxygen plus 2% nitrogen (Ctrl) under normothermia for 1 h. EEG characteristics were continuously recorded for 4 h, and the relationships between quantitative EEG characteristics and 96 h neurological outcomes were investigated. RESULTS: No differences in baseline and resuscitation data were observed between groups, but the survival rate was significantly higher in the H2 group than in the Ctrl group (90% vs. 40%, P < 0.01). Compared to the Ctrl group, the H2 group showed a shorter burst onset time (21.85 [20.00-23.38] vs. 25.70 [22.48-30.05], P < 0.01) and time to normal trace (169.83 [161.63-208.55] vs. 208.39 [186.29-248.80], P < 0.01). Additionally, the burst suppression ratio (0.66 ± 0.09 vs. 0.52 ± 0.17, P < 0.01) and weighted-permutation entropy (0.47 ± 0.16 vs. 0.34 ± 0.13, P < 0.01) were markedly higher in the H2 group. The areas under the receiver operating characteristic curves for the 4 EEG characteristics in predicting survival were 0.82, 0.84, 0.88, and 0.83, respectively. CONCLUSIONS: In this asphyxial CA rat model, the improved postresuscitation EEG characteristics for animals treated with hydrogen are correlated with the better 96 h neurological outcome and predicted survival.", "conclusion": "In this asphyxial CA rat model, the improved postresuscitation EEG characteristics for animals treated with hydrogen are correlated with the better 96 h neurological outcome and predicted survival." }, { "pmid": "31622584", "year": 2019, "title": "Staphylococcus aureus evasion proteins EapH1 and EapH2: Residue-level investigation of an alternative binding motif for human neutrophil elastase.", "title_en": null, "title_de": "Staphylococcus-aureus-Evasionsproteine EapH1 und EapH2: Untersuchung eines alternativen Bindungsmotivs für die humane neutrophile Elastase auf Residuenebene", "journal": "Archives of biochemistry and biophysics", "authors": "Herdendorf et al.", "author_search": "herdendorf herdendorf", "doi": "10.1016/j.abb.2019.108140", "doi_url": "https://doi.org/10.1016/j.abb.2019.108140", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31622584/", "url": "https://h2medicine.org/studies/study-herdendorf-2019-staphylococcus-aureus-evasion-proteins/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2019 · Herdendorf — Staphylococcus aureus Evasion Proteins EapH1 and EapH2: Residue-Level Investigation of an Alternative Binding Motif for Human Neutrophil Elastase", "summary": "Two bacterial immune-evasion proteins (EapH1 and EapH2) from Staphylococcus aureus inhibit a key human immune enzyme — neutrophil elastase — but use structurally different binding strategies. This in-vitro biochemistry study maps exactly which amino-acid residues in EapH2 are responsible for that inhibition. The findings illuminate how a pathogen evades neutrophil defences and could inform future anti-infective design. (Archives of Biochemistry and Biophysics, 2019.)", "assessment": "This is a well-executed in-vitro biochemistry paper investigating bacterial immune evasion — it is not a hydrogen therapy study. No H₂ was administered; the „hydrogen“ referenced in the abstract refers to hydrogen bonds within protein crystal structures, which is standard chemistry. The paper has no direct relevance to molecular hydrogen (H₂) as a medical or nutritional intervention. It should be read as background structural biology rather than evidence for any H₂ health effect.", "abstract": "The Staphylococcus aureusExtracellular Adherence Protein (Eap) and its homologs, EapH1 and EapH2, are a family of secreted proteins that potently inhibit the neutrophil serine proteases Neutrophil Elastase (hNE), Cathepsin G, and Proteinase 3. Similarly to EapH1, inhibition of hNE by EapH2 is characterized by a rapid association rate (2.9 × 105 M-1s-1) coupled with a very slow dissociation rate (5.9 × 10-4 s-1), yielding an apparent inhibition constant of 2.11 nM. As with EapH1, inhibition of hNE by EapH2 is also time-dependent in character. A phenylalanine in EapH2 replaces the leucine in EapH1 that sits over the hNE catalytic serine and creates a potential steric clash. Indeed, the EapH1 L59F mutant is severely decreased in its ability to inhibit hNE (~9500-fold). When compared to the EapH1:hNE co-crystal structure, a model of the EapH2:hNE complex predicts an alternative binding motif comprised of EapH2 residues 120-127. These putative interfacing residues were individually mutated and kinetically interrogated. The EapH2 N127A mutant resulted in the largest decrease in hNE inhibition (~200-fold) and loss of the time-dependent characteristic. Surprisingly, the time-dependent characteristic was still abolished in the EapH2 T125A mutant, even though it was less perturbed in hNE inhibition (~25-fold). T125 forms an intra-molecular hydrogen bond to the carbonyl oxygen of N127 in the EapH2 crystal structure. Given these observations, we conclude (i) that EapH2 has an altogether distinct hNE binding motif than EapH1, (ii) that N127 is the main functional determinant in EapH2, and (iii) that T125 serves an ancillary role aiding in the optimal orientation of N127.", "conclusion": "T125 forms an intra-molecular hydrogen bond to the carbonyl oxygen of N127 in the EapH2 crystal structure. Given these observations, we conclude (i) that EapH2 has an altogether distinct hNE binding motif than EapH1, (ii) that N127 is the main functional determinant in EapH2, and (iii) that T125 serves an ancillary role aiding in the optimal orientation of N127." }, { "pmid": "31600256", "year": 2019, "title": "Positive effect of an electrolyzed reduced water on gut permeability, fecal microbiota and liver in an animal model of Parkinson's disease.", "title_en": null, "title_de": "Positive Wirkung von elektrolysiertem reduziertem Wasser auf die Darmpermeabilität, die fäkale Mikrobiota und die Leber in einem Tiermodell der Parkinson-Krankheit", "journal": "PloS one", "authors": "Bordoni et al.", "author_search": "bordoni bordoni", "doi": "10.1371/journal.pone.0223238", "doi_url": "https://doi.org/10.1371/journal.pone.0223238", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31600256/", "url": "https://h2medicine.org/studies/study-bordoni-2019-positive-electrolyzed-reduced-gut/", "methods": [ "drinking-hrw" ], "indications": [ "liver", "neurology", "immune-system" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2019 · Bordoni — Positive Effect of an Electrolyzed Reduced Water on Gut Permeability, Fecal Microbiota and Liver in an Animal Model of Parkinson's Disease", "summary": "In a rat model of Parkinson's disease induced by the pesticide permethrin, co-treatment with electrolyzed reduced water (ERW) protected the gut barrier, reduced liver inflammation, and shifted the gut microbiota toward a healthier profile. ERW-treated animals showed lower intestinal permeability, more butyrate-producing bacteria, and fewer inflammatory markers in the liver than untreated Parkinson's model rats. These are animal findings and cannot be directly transferred to humans. (PLoS ONE, 2019.)", "assessment": "This is an animal study (rat) — results are not directly transferable to humans. The design is carefully controlled (three groups: control, PERM, PERM+ERW) and uses established assays. The findings are biologically coherent: gut permeability, hepatic inflammation, and microbiota composition all moved in a favourable direction with ERW. Honest limitations: (1) ERW is a complex mixture, not pure H₂ water; (2) no motor or behavioural Parkinson's endpoints were measured in this paper; (3) the permethrin model approximates early Parkinson's but is not a validated gold-standard model of the human disease; (4) n per group is not explicitly stated in the abstract — statistical power is unclear. The work is hypothesis-generating and supports further investigation.", "abstract": "There is growing awareness within the scientific community of the strong connection between the inflammation in the intestine and the pathogenesis of Parkinson's disease (PD). In previous studies we developed a PD animal model exposing pup rats to permethrin (PERM) pesticide. Here, we intended to explore whether in our animal model there were changes in gut permeability, fecal microbiota and hepatic injury. Moreover, we tested if the co-treatment with an electrolyzed reduced (ERW) was effective to protect against alterations induced by PERM. Rats (from postnatal day 6 to 21) were gavaged daily with PERM, PERM+ERW or vehicle and gut, liver and feces were analyzed in 2-months-old rats. Increased gut permeability, measured by FITC-dextran assay, was detected in PERM group compared to control and PERM+ERW groups. In duodenum and ileum, concentration of occludin was higher in control group than those measured in PERM group, whereas only in duodenum ZO-1 was higher in control than those measured in PERM and PERM+ERW groups. Number of inflammatory focis and neutrophils as well as iNOS protein levels were higher in livers of PERM-treated rats than in those of PERM+ERW and control rats. Fecal microbiota analysis revealed that Lachnospira was less abundant and Defluviitaleaceae more abundant in the PERM group, whereas the co-treatment with ERW was protective against PERM treatment since the abundances in Lachnospira and Defluviitaleaceae were similar to those in the control group. Higher abundances of butyrate- producing bacteria such as Blautia, U.m. of Lachnospiraceae family, U.m. of Ruminococcaceae family, Papillibacter, Roseburia, Intestinimonas, Shuttleworthia together with higher butyric acid levels were detected in PERM+ERW group compared to the other groups. In conclusion, the PD animal model showed increased intestinal permeability together with hepatic inflammation correlated with altered gut microbiota. The positive effects of ERW co-treatment observed in gut, liver and brain of rats were linked to changes on gut microbiota.", "conclusion": "In conclusion, the PD animal model showed increased intestinal permeability together with hepatic inflammation correlated with altered gut microbiota. The positive effects of ERW co-treatment observed in gut, liver and brain of rats were linked to changes on gut microbiota." }, { "pmid": "31574947", "year": 2019, "title": "In Vivo Simulation of Magnesium Degradability Using a New Fluid Dynamic Bench Testing Approach.", "title_en": null, "title_de": "In-vivo-Simulation der Magnesium-Abbaubarkeit mithilfe eines neuen strömungsdynamischen Prüfstandsansatzes", "journal": "International journal of molecular sciences", "authors": "Jung et al.", "author_search": "jung jung", "doi": "10.3390/ijms20194859", "doi_url": "https://doi.org/10.3390/ijms20194859", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31574947/", "url": "https://h2medicine.org/studies/study-jung-2019-vivo-simulation-magnesium-degradability/", "methods": [ "inhalation" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2019 · Jung — In Vivo Simulation of Magnesium Degradability Using a New Fluid Dynamic Bench Testing Approach", "summary": "A new dynamic test bench was constructed to measure hydrogen gas (H₂) release during the degradation of magnesium-based implants — using H₂ evolution as a proxy for degradation rate under physiological conditions. Plasma-electrolytically oxidized (PEO) magnesium alloys showed significantly reduced and more uniform degradation compared to untreated WE43 alloy. This is an in-vitro biomaterials engineering study; the H₂ measured here is a degradation by-product, not a therapeutic intervention. (International Journal of Molecular Sciences, 2019.)", "assessment": "This is an in-vitro biomaterials engineering study — it does not investigate molecular hydrogen as a therapeutic agent. H₂ gas here is an unwanted degradation by-product that must be minimised for implant safety. The study is methodologically solid, introducing a validated bench model that correlates well with in-vivo data. Its relevance to H₂ medicine is indirect: it helps understand how much H₂ can be released from Mg-based medical devices. No health claims for H₂ can be derived from this paper.", "abstract": "The degradation rate of magnesium (Mg) alloys is a key parameter to develop Mg-based biomaterials and ensure in vivo-mechanical stability as well as to minimize hydrogen gas production, which otherwise can lead to adverse effects in clinical applications. However, in vitro and in vivo results of the same material often differ largely. In the present study, a dynamic test bench with several single bioreactor cells was constructed to measure the volume of hydrogen gas which evolves during magnesium degradation to indicate the degradation rate in vivo. Degradation medium comparable with human blood plasma was used to simulate body fluids. The media was pumped through the different bioreactor cells under a constant flow rate and 37 °C to simulate physiological conditions. A total of three different Mg groups were successively tested: Mg WE43, and two different WE43 plasma electrolytically oxidized (PEO) variants. The results were compared with other methods to detect magnesium degradation (pH, potentiodynamic polarization (PDP), cytocompatibility, SEM (scanning electron microscopy)). The non-ceramized specimens showed the highest degradation rates and vast standard deviations. In contrast, the two PEO samples demonstrated reduced degradation rates with diminished standard deviation. The pH values showed above-average constant levels between 7.4-7.7, likely due to the constant exchange of the fluids. SEM revealed severe cracks on the surface of WE43 after degradation, whereas the ceramized surfaces showed significantly decreased signs of corrosion. PDP results confirmed the improved corrosion resistance of both PEO samples. While WE43 showed slight toxicity in vitro, satisfactory cytocompatibility was achieved for the PEO test samples. In summary, the dynamic test bench constructed in this study enables reliable and simple measurement of Mg degradation to simulate the in vivo environment. Furthermore, PEO treatment of magnesium is a promising method to adjust magnesium degradation.", "conclusion": "In summary, the dynamic test bench constructed in this study enables reliable and simple measurement of Mg degradation to simulate the in vivo environment. Furthermore, PEO treatment of magnesium is a promising method to adjust magnesium degradation." }, { "pmid": "31574107", "year": 2019, "title": "Organ preservation solution containing dissolved hydrogen gas from a hydrogen-absorbing alloy canister improves function of transplanted ischemic kidneys in miniature pigs.", "title_en": null, "title_de": "Eine Organkonservierungslösung mit gelöstem Wasserstoffgas aus einem wasserstoffabsorbierenden Legierungsbehälter verbessert die Funktion transplantierter ischämischer Nieren bei Miniaturschweinen", "journal": "PloS one", "authors": "Kobayashi et al.", "author_search": "kobayashi kobayashi", "doi": "10.1371/journal.pone.0222863", "doi_url": "https://doi.org/10.1371/journal.pone.0222863", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31574107/", "url": "https://h2medicine.org/studies/study-kobayashi-2019-organ-preservation-solution-containing/", "methods": [ "inhalation" ], "indications": [ "kidney-dialysis", "fundamentals-safety" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2019 · Kobayashi — Organ Preservation Solution Containing Dissolved Hydrogen Gas from a Hydrogen-Absorbing Alloy Canister Improves Function of Transplanted Ischemic Kidneys in Miniature Pigs", "summary": "Adding dissolved molecular hydrogen (H₂) to the organ preservation solution — via a rapid, practical canister method — significantly improved kidney function after transplantation from donors with circulatory arrest in miniature pigs. Kidneys stored in H₂-containing solution produced urine and showed blood flow on day 6 post-transplant, while those stored in standard solution without H₂ did not. This is an animal study; direct human applicability requires further research. (PLoS ONE, 2019.)", "assessment": "A well-designed animal study (miniature pig) with a clear, clinically relevant question. The functional endpoint (urine production + blood flow at day 6) is meaningful and the results are striking. Honest limitations: (1) this is a pig model, not a human trial — direct transfer is not warranted; (2) the sample sizes are not detailed in the abstract, making statistical evaluation impossible; (3) only one cold ischemia time series was tested; (4) longer follow-up and rejection/fibrosis outcomes are not assessed. If confirmed in larger trials, H₂-enriched preservation solution could be a practical, low-cost addition to transplant protocols — but clinical validation is needed.", "abstract": "Various methods have been devised to dissolve hydrogen gas in organ preservation solutions, including use of a hydrogen gas cylinder, electrolysis, or a hydrogen-generating agent. However, these methods require considerable time and effort for preparation. We investigated a practical technique for rapidly dissolving hydrogen gas in organ preservation solutions by using a canister containing hydrogen-absorbing alloy. The efficacy of hydrogen-containing organ preservation solution created by this method was tested in a miniature pig model of kidney transplantation from donors with circulatory arrest. The time required for dissolution of hydrogen gas was only 2-3 minutes. When hydrogen gas was infused into a bag containing cold ETK organ preservation solution at a pressure of 0.06 MPa and the bag was subsequently opened to the air, the dissolved hydrogen concentration remained at 1.0 mg/L or more for 4 hours. After warm ischemic injury was induced by circulatory arrest for 30 minutes, donor kidneys were harvested and perfused for 5 minutes with hydrogen-containing cold ETK solution or hydrogen-free cold ETK solution. The perfusion rate was faster from the initial stage with hydrogen-containing cold ETK solution than with hydrogen-free ETK solution. After storage of the kidney in hydrogen-free preservation solution for 1 hour before transplantation, no urine production was observed and blood flow was not detected in the transplanted kidney at sacrifice on postoperative day 6. In contrast, after storage in hydrogen-containing preservation solution for either 1 or 4 hours, urine was detected in the bladder and blood flow was confirmed in the transplanted kidney. This method of dissolving hydrogen gas in organ preservation solution is a practical technique for potentially converting damaged organs to transplantable organs that can be used safely in any clinical setting where organs are removed from donors.", "conclusion": "In contrast, after storage in hydrogen-containing preservation solution for either 1 or 4 hours, urine was detected in the bladder and blood flow was confirmed in the transplanted kidney. This method of dissolving hydrogen gas in organ preservation solution is a practical technique for potentially converting damaged organs to transplantable organs that can be used safely in any clinical setting wh" }, { "pmid": "31552873", "year": 2019, "title": "\"Real world survey\" of hydrogen-controlled cancer: a follow-up report of 82 advanced cancer patients.", "title_en": null, "title_de": "„Real-World-Erhebung“ zur wasserstoffgesteuerten Krebsbehandlung: ein Folgebericht über 82 Patienten mit fortgeschrittenem Krebs.", "journal": "Medical gas research", "authors": "Chen et al.", "author_search": "chen chen", "doi": "10.4103/2045-9912.266985", "doi_url": "https://doi.org/10.4103/2045-9912.266985", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31552873/", "url": "https://h2medicine.org/studies/study-chen-2019-real-world-survey-cancer/", "methods": [ "inhalation" ], "indications": [ "liver", "sports-exercise", "cancer", "respiratory", "skin-aging", "immune-system", "womens-health", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2019 · Chen et al. — „Real world survey“ of hydrogen-controlled cancer: a follow-up report of 82 advanced cancer patients.", "summary": "A prospective follow-up of 82 stage III/IV cancer patients inhaling H₂ for 3–46 months found that 41.5 % showed improved physical status, 36.2 % of those with elevated tumour markers saw markers decrease, and the overall disease control rate in imageable tumours was 57.5 % — with the best responses in lung cancer and the poorest in pancreatic cancer. This real-world observational study has no control group and uses heterogeneous endpoints across diverse cancer types. (Medical Gas Research, 2019.)", "assessment": "A large, long-term uncontrolled observational series that documents real-world use of H₂ inhalation in advanced cancer. The symptom improvement and quality-of-life data are consistent with other reports and plausible. The disease control rates cannot be interpreted without a comparator. Limitations: no control group; heterogeneous cancer types (lung, pancreatic, liver, gynecologic, others); treatment histories not standardised; endpoints are a mix of subjective and objective with different measurement intervals; selection bias (patients who chose H₂ and tolerated it for months may differ systematically from those who did not). The safety profile is consistently reassuring across this series.", "abstract": "Advanced cancer treatment is a huge challenge and new ideas and strategies are required. Hydrogen exerts antioxidant and anti-inflammatory effects that may be exploited to control cancer, the occurrence and progression of which is closely related to peroxidation and inflammation. We conducted a prospective follow-up study of 82 patients with stage III and IV cancer treated with hydrogen inhalation using the \"real world evidence\" method. After 3-46 months of follow-up, 12 patients died in stage IV. After 4 weeks of hydrogen inhalation, patients reported significant improvements in fatigue, insomnia, anorexia and pain. Furthermore, 41.5% of patients had improved physical status, with the best effect achieved in lung cancer patients and the poorest in patients with pancreatic and gynecologic cancers. Of the 58 cases with one or more abnormal tumor markers elevated, the markers were decreased at 13-45 days (median 23 days) after hydrogen inhalation in 36.2%. The greatest marker decrease was in achieved lung cancer and the lowest in pancreatic and hepatic malignancies. Of the 80 cases with tumors visible in imaging, the total disease control rate was 57.5%, with complete and partial remission appearing at 21-80 days (median 55 days) after hydrogen inhalation. The disease control rate was significantly higher in stage III patients than in stage IV patients (83.0% and 47.7%, respectively), with the lowest disease control rate in pancreatic cancer patients. No hematological toxicity was observed although minor adverse reactions that resolved spontaneously were seen in individual cases. In patients with advanced cancer, inhaled hydrogen can improve patients' quality-of-life and control cancer progression. Hydrogen inhalation is a simple, low-cost treatment with few adverse reactions that warrants further investigation as a strategy for clinical rehabilitation of patients with advanced cancer. The study protocol received ethical approval from the Ethics Committee of Fuda Cancer Hospital of Jinan University on December 7, 2018 (approval number: Fuda20181207).", "conclusion": "Hydrogen inhalation is a simple, low-cost treatment with few adverse reactions that warrants further investigation as a strategy for clinical rehabilitation of patients with advanced cancer. The study protocol received ethical approval from the Ethics Committee of Fuda Cancer Hospital of Jinan University on December 7, 2018 (approval number: Fuda20181207)." }, { "pmid": "31499254", "year": 2019, "title": "Hydrogen gas improves photothermal therapy of tumor and restrains the relapse of distant dormant tumor.", "title_en": null, "title_de": "Wasserstoffgas verbessert die photothermische Therapie von Tumoren und hemmt das Wiederauftreten ruhender Ferntumoren", "journal": "Biomaterials", "authors": "Zhang et al.", "author_search": "zhang zhang", "doi": "10.1016/j.biomaterials.2019.119472", "doi_url": "https://doi.org/10.1016/j.biomaterials.2019.119472", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31499254/", "url": "https://h2medicine.org/studies/study-zhang-2019-improves-photothermal-tumor-restrains/", "methods": [ "inhalation" ], "indications": [ "sports-exercise", "cancer", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2019 · Zhang — Hydrogen Gas Improves Photothermal Therapy of Tumor and Restrains the Relapse of Distant Dormant Tumor", "summary": "A biomimetic nanoparticle (mPDAB) that releases molecular hydrogen (H₂) locally in the tumor was combined with photothermal therapy (PTT) in a mouse breast cancer model, leading to complete elimination of primary tumors and suppression of distant dormant tumor regrowth. The H₂ released by ammonia borane within the nanoparticle reduced inflammation caused by PTT and disrupted redox balance in cancer cells. These are animal/in-vitro results; human relevance is unestablished. (Biomaterials, 2019.)", "assessment": "This is an animal study (mouse breast cancer model) with sophisticated in-vitro mechanistic support. The results — complete primary tumor elimination and dormant tumor suppression — are striking. However, honest limitations apply: (1) mouse xenograft models do not replicate the complexity of human breast cancer; (2) the nanoparticle formulation has not been tested in humans; (3) long-term toxicity and biodistribution of mPDAB are not addressed; (4) the dormant tumor model used here is a specific experimental setup — clinical distant metastasis is far more complex. This paper represents innovative preclinical nanomedicine research, not evidence for H₂ therapy in human cancer. No health claims should be derived from it.", "abstract": "Inflammation during photothermal therapy (PTT) of tumor usually results in adverse consequences. Here, a biomembrane camouflaged nanomedicine (mPDAB) containing polydopamine and ammonia borane was designed to enhance PTT efficacy and mitigate inflammation. Polydopamine, a biocompatible photothermal agent, can effectively convert light into heat for PTT. Ammonia borane was linked to the surface of polydopamine through the interaction of hydrogen bonding, which could destroy redox homoeostasis in tumor cells and reduce inflammation by H2 release in tumor microenvironment. Owing to the same origin of outer biomembranes, mPDAB showed excellent tumor accumulation and low systemic toxicity in a breast tumor model. Excellent PTT efficacy and inflammation reduction made the mPDAB completely eliminate the primary tumors, while also restraining the outgrowth of distant dormant tumors. The biomimetic nanomedicine shows potentials as a universal inflammation-self-alleviated platform to ameliorate inflammation-related disease treatment, including but not limited to PTT for tumor.", "conclusion": "Excellent PTT efficacy and inflammation reduction made the mPDAB completely eliminate the primary tumors, while also restraining the outgrowth of distant dormant tumors. The biomimetic nanomedicine shows potentials as a universal inflammation-self-alleviated platform to ameliorate inflammation-related disease treatment, including but not limited to PTT for tumor." }, { "pmid": "31479580", "year": 2019, "title": "Lifetime of Parahydrogen in Aqueous Solutions and Human Blood.", "title_en": null, "title_de": "Lebensdauer von Parawasserstoff in wässrigen Lösungen und menschlichem Blut", "journal": "Chemphyschem : a European journal of chemical physics and physical chemistry", "authors": "Schmidt et al.", "author_search": "schmidt schmidt", "doi": "10.1002/cphc.201900670", "doi_url": "https://doi.org/10.1002/cphc.201900670", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31479580/", "url": "https://h2medicine.org/studies/study-schmidt-2019-lifetime-parahydrogen-aqueous-solutions/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2019 · Schmidt — Lifetime of Parahydrogen in Aqueous Solutions and Human Blood", "summary": "Parahydrogen (pH₂) — a nuclear spin isomer of molecular hydrogen — survives for unexpectedly long periods in water and even in human blood, with lifetimes of 10 to 300 minutes. This in-vitro physics study characterises the relaxation behaviour of pH₂ in biological media, which is essential for designing parahydrogen-based MRI signal-enhancement techniques (PHIP). Therapeutic effects of H₂ are not investigated here. (ChemPhysChem, 2019.)", "assessment": "This is a rigorous in-vitro biophysics study relevant to MRI/NMR methodology, not to H₂ as a health intervention. The finding that pH₂ persists for 10–300 minutes in aqueous and blood media is important for PHIP-based imaging development. No therapeutic claims for H₂ can be derived from this paper. The „molecular hydrogen“ here refers to a quantum spin state used as a physics tool, not to dissolved H₂ ingestion or inhalation. The work is methodologically sound; it advances the instrumental basis for future in-vivo imaging but does not bear on the clinical H₂ literature.", "abstract": "Molecular hydrogen has unique nuclear spin properties. Its nuclear spin isomer, parahydrogen (pH2 ), was instrumental in the early days of quantum mechanics and allows to boost the NMR signal by several orders of magnitude. pH2- induced polarization (PHIP) is based on the survival of pH2 spin order in solution, yet its lifetime has not been investigated in aqueous or biological media required for in vivo applications. Herein, we report longitudinal relaxation times (T1 ) and lifetimes of pH2 ( τPOC ) in methanol and water, with or without O2 , NaCl, rhodium-catalyst or human blood. Furthermore, we present a relaxation model that uses T1 and τPOC for more precise theoretical predictions of the H2 spin state in PHIP experiments. All measured T1 values were in the range of 1.4-2 s and τPOC values were of the order of 10-300 minutes. These relatively long lifetimes hold great promise for emerging in vivo implementations and applications of PHIP.", "conclusion": "All measured T1 values were in the range of 1.4-2 s and τPOC values were of the order of 10-300 minutes. These relatively long lifetimes hold great promise for emerging in vivo implementations and applications of PHIP." }, { "pmid": "31352109", "year": 2019, "title": "Effect of physical cues of altered extract media from biodegradable magnesium implants on human gingival fibroblasts.", "title_en": null, "title_de": "Wirkung physikalischer Reize von verändertem Extraktmedium aus biologisch abbaubaren Magnesiumimplantaten auf menschliche Gingivafibroblasten", "journal": "Acta biomaterialia", "authors": "Amberg et al.", "author_search": "amberg amberg", "doi": "10.1016/j.actbio.2019.07.022", "doi_url": "https://doi.org/10.1016/j.actbio.2019.07.022", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31352109/", "url": "https://h2medicine.org/studies/study-amberg-2019-physical-cues-altered-extract/", "methods": [ "unspecified" ], "indications": [ "sports-exercise", "oral-health" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2019 · Amberg — Effect of Physical Cues of Altered Extract Media from Biodegradable Magnesium Implants on Human Gingival Fibroblasts", "summary": "As biodegradable magnesium (Mg) implants corrode, they alter the surrounding medium with elevated Mg²⁺, reduced Ca²⁺, increased osmolality, and dissolved molecular hydrogen (H₂) — all of which affect the migration rate of human gingival fibroblasts. This in-vitro study finds that the shifted Mg²⁺/Ca²⁺ ratio is the dominant factor slowing cell migration, while a constantly elevated H₂ concentration contributes as a secondary factor. These are cell-culture results; no direct health claims can be derived. (Acta Biomaterialia, 2019.)", "assessment": "A well-designed in-vitro study that provides mechanistic insight into how Mg-implant degradation products affect wound-healing cell behaviour. The H₂ involvement is secondary and arises from corrosion, not from therapeutic administration. No health promotion claims for H₂ can be drawn from this paper. Its relevance to H₂ medicine is as a safety/context paper: it helps understand H₂ concentrations that arise near corroding Mg implants and their cellular effects. The authors appropriately caveat the cell-type specificity of their findings.", "abstract": "Volume stable barrier membranes made of magnesium are very promising in Guided Bone Regeneration (GBR) to treat periodontal bone defects in dentistry due to their excellent biocompatibility and biodegradability. During the degradation process the cells are exposed to the alteration of various parameters, so called physical cues, involving surface alterations due to the formed corrosion layer and medium alterations arising from the dissolved corrosion products. Cell migration of human gingival fibroblasts (HGF), as a crucial parameter for optimal healing process in GBR, has been investigated on magnesium membranes and revealed that medium alterations by dissolved corrosion products have a higher impact on cell migration than surface alterations. However, the effect of each altered medium parameter on cell migration has not been adequately studied, but their roles are crucial to explain the slower migration rate on magnesium surfaces compared to titanium and tissue culture plastic surfaces. Our study investigates the single effect of Mg2+, Ca2+, H2 and increased osmolality as well as the effect of magnesium extracts, which contain a dynamic mixture of previous parameters on cell migration, proliferation and viability of HGF. We showed that at 75 mM Mg2+ concentration and at 0 mM Ca2+, respectively, the cell migration rate is greatly reduced. In complex magnesium extract media, we found that a temporarily increased ratio of Mg2+ to Ca2+ conditioned a slow HGF migration rate. Based on these findings and the characterization of supernatants from HGF migration assays on Mg membranes, we propose, that the slower migration rate of HGF can be explained by the altered ratio of Mg2+ to Ca2+, caused by increasing concentrations of Mg2+ and decreasing concentrations of Ca2+ in the vicinity of the corroding Mg implant, combined with a constantly increased molecular hydrogen concentration in the supernatant. These results are cell type specific and should be checked carefully, if necessary, for Mg implant performance. STATEMENT OF SIGNIFICANCE: The study is providing a systematic approach to explain the main effects of extract medium parameters (physical cues) such as magnesium or calcium ion concentration, osmolality and dissolved molecular hydrogen and CO2 in cell culture media modified by co-incubating with corroding magnesium implants on the migration rate of human gingival fibroblasts (HGF). This study uncovers for the first time the combinatory effect of slightly increased molecular hydrogen and the change in Mg2+/Ca2+ ratio on HGF cell migration.", "conclusion": "STATEMENT OF SIGNIFICANCE: The study is providing a systematic approach to explain the main effects of extract medium parameters (physical cues) such as magnesium or calcium ion concentration, osmolality and dissolved molecular hydrogen and CO2 in cell culture media modified by co-incubating with corroding magnesium implants on the migration rate of human gingival fibroblasts (HGF). This study unc" }, { "pmid": "31329427", "year": 2019, "title": "Hydrogen Gas from Inflammation Treatment to Cancer Therapy.", "title_en": null, "title_de": "Wasserstoffgas: Von der Entzündungsbehandlung zur Krebstherapie", "journal": "ACS nano", "authors": "Wu et al.", "author_search": "wu wu", "doi": "10.1021/acsnano.9b05124", "doi_url": "https://doi.org/10.1021/acsnano.9b05124", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31329427/", "url": "https://h2medicine.org/studies/study-wu-2019-inflammation-cancer/", "methods": [ "inhalation" ], "indications": [ "liver", "cancer", "immune-system", "fundamentals-safety" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2019 · Wu — Hydrogen Gas from Inflammation Treatment to Cancer Therapy", "summary": "This review surveys the emerging field of molecular hydrogen (H₂) therapy, from its anti-inflammatory mechanisms to its potential role in cancer treatment, with special focus on how nanomaterials can deliver H₂ more precisely to target sites. The authors argue that nanocarrier-mediated H₂ delivery and in-situ H₂ generation by nanogenerators could overcome the poor targeting of systemic H₂ gas administration. (ACS Nano, 2019.)", "assessment": "This is a review article (ev=4) — it synthesises existing literature rather than presenting new experimental data. As a perspective in ACS Nano it is influential and well-written. Honest assessment: the anti-tumor effects of H₂ described are based predominantly on animal and cell-culture data; no clinical trials in cancer patients are cited. The review's greatest value is conceptual — it frames nanomaterial-assisted H₂ delivery as a research direction. The authors acknowledge mechanistic gaps. The „highly promising“ framing should be read as a research aspiration, not as established clinical efficacy.", "abstract": "Hydrogen (H2) therapy is a highly promising strategy against several diseases due to its inherent biosafety. However, the current H2 treatment modalities rely predominantly on the systemic administration of the gas, resulting in poor targeting and utilization. Furthermore, although H2 has significant anti-tumor effects, the underlying mechanisms have not yet been elucidated. Due to their ultrasmall size, nanomaterials are highly suitable drug-delivery systems with a myriad of biomedical applications. Nanocarrier-mediated H2 delivery, as well as in situ production of H2 by nanogenerators, can significantly improve targeted accumulation of the gas and accelerate the therapeutic effects. In addition, nanomaterials can be further modified to enhance passive or active accumulation at the target site. In this Perspective, we summarize the mechanism of H2 therapy and describe possibilities for combining H2 therapy with nanomaterials. We also discuss the current challenges of H2 therapy and provide some insights into this burgeoning field.", "conclusion": "In this Perspective, we summarize the mechanism of H2 therapy and describe possibilities for combining H2 therapy with nanomaterials. We also discuss the current challenges of H2 therapy and provide some insights into this burgeoning field." }, { "pmid": "31323168", "year": 2019, "title": "Skin ulcers infected with conditional pathogenic strains treated with local hydrogen water packing in two pemphigus vulgaris patients: Case reports with follow-up for 2 months.", "title_en": null, "title_de": "Mit bedingt pathogenen Stämmen infizierte Hautgeschwüre, behandelt mit lokaler Wasserstoffwasser-Auflage bei zwei Patienten mit Pemphigus vulgaris: Fallberichte mit zweimonatiger Nachbeobachtung.", "journal": "Dermatologic therapy", "authors": "Yang et al.", "author_search": "yang yang", "doi": "10.1111/dth.13027", "doi_url": "https://doi.org/10.1111/dth.13027", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31323168/", "url": "https://h2medicine.org/studies/study-yang-2019-skin-ulcers-infected-conditional/", "methods": [ "drinking-hrw" ], "indications": [ "skin-aging", "immune-system" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2019 · Yang et al. — Skin ulcers infected with conditional pathogenic strains treated with local hydrogen water packing in two pemphigus vulgaris patients: Case reports with follow-up for 2 months.", "summary": "Two patients with pemphigus vulgaris — an autoimmune blistering disorder — developed secondary skin ulcer infections with opportunistic pathogens that were treated with local wet packing using hydrogen water, resulting in healing over two months of follow-up. The authors describe this as a novel approach to infected chronic inflammatory skin ulcers. This is a two-patient case series with no control condition. (Dermatologic Therapy, 2019.)", "assessment": "Two-patient case series with a very short abstract — the weakest study in this chunk by evidence level. The approach (local H₂ water packing for infected skin ulcers in immunocompromised patients) is novel and the safety profile appears acceptable, but efficacy cannot be assessed from 2 uncontrolled cases. The claim of „effective treatment“ in the abstract is stronger than the evidence justifies. Limitations: n = 2; no control; no quantitative wound healing data reported in the abstract; concurrent immunosuppressive treatment not described; 2-month follow-up only; pathogen clearance not detailed.", "abstract": "We are the first to report on a new, safe, and effective treatment of infections induced by conditional pathogenic strains with local wet packing with hydrogen water. The new treatment method may also shed light on the therapy of chronic, inflammatory skin ulcers.", "conclusion": "We are the first to report on a new, safe, and effective treatment of infections induced by conditional pathogenic strains with local wet packing with hydrogen water. The new treatment method may also shed light on the therapy of chronic, inflammatory skin ulcers." }, { "pmid": "31295412", "year": 2019, "title": "Molecular hydrogen suppresses free-radical-induced cell death by mitigating fatty acid peroxidation and mitochondrial dysfunction.", "title_en": null, "title_de": "Molekularer Wasserstoff unterdrückt den durch freie Radikale induzierten Zelltod durch Minderung der Fettsäure-Peroxidation und der mitochondrialen Dysfunktion", "journal": "Canadian journal of physiology and pharmacology", "authors": "Iuchi et al.", "author_search": "iuchi iuchi", "doi": "10.1139/cjpp-2018-0741", "doi_url": "https://doi.org/10.1139/cjpp-2018-0741", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31295412/", "url": "https://h2medicine.org/studies/study-iuchi-2019-suppresses-free-radical-induced/", "methods": [ "unspecified" ], "indications": [ "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2019 · Iuchi — Molecular Hydrogen Suppresses Free-Radical-Induced Cell Death by Mitigating Fatty Acid Peroxidation and Mitochondrial Dysfunction", "summary": "In human leukemia cells exposed to the oxidative stressor tert-butyl hydroperoxide, molecular hydrogen (H₂) reduced fatty acid peroxidation, preserved mitochondrial function, and prevented cell death. This in-vitro study provides mechanistic evidence that H₂ protects cells from radical-induced damage through two complementary pathways: suppression of lipid peroxidation and protection of mitochondrial integrity. These are cell-culture results and do not constitute proof of human therapeutic efficacy. (Canadian Journal of Physiology and Pharmacology, 2019.)", "assessment": "A mechanistically informative in-vitro study using established assays. The findings contribute to the mechanistic picture of how H₂ reduces oxidative injury at the cellular level. Honest limitations: (1) THP-1 is a leukemia cell line, not primary human cells; (2) the oxidative stressor (tBHP) is a synthetic model compound — not the same as physiological oxidative stress; (3) H₂ concentration in the cell medium is not explicitly quantified in the abstract; (4) no in-vivo validation. The study supports the mechanistic plausibility of H₂'s antioxidant effects but does not demonstrate efficacy in any human disease.", "abstract": "Molecular hydrogen (H2) was believed to be an inert and nonfunctional molecule in mammalian cells; however, we overturned the concept by reporting the therapeutic effects of H2 against oxidative stress. Subsequently, extensive studies revealed multiple functions of H2 by exhibiting the efficacies of H2 in various animal models and clinical studies. Here, we investigated the effect of H2 on free-radical-induced cytotoxicity using tert-butyl hydroperoxide in a human acute monocytic leukemia cell line, THP-1. Cell membrane permeability was determined using lactate dehydrogenase release assay and Hoechst 33342 and propidium iodide staining. Fatty acid peroxidation and mitochondrial viability were measured using 2 kinds of fluorescent dyes, Liperfluo and C11-BODIPY, and using the alamarBlue assay based on the reduction of resazurin to resorufin by mainly mitochondrial succinate dehydrogenase, respectively. Mitochondrial membrane potential was evaluated using tetramethylrhodamine methyl ester. As a result, H2 protected the cultured cells against the cytotoxic effects induced by tert-butyl hydroperoxide; H2 suppressed cellular fatty acid peroxidation and cell membrane permeability, mitigated the decline in mitochondrial oxidoreductase activity and mitochondrial membrane potential, and protected cells against cell death evaluated using propidium iodide staining. These results suggested that H2 suppresses free-radical-induced cell death through protection against fatty acid peroxidation and mitochondrial dysfunction.", "conclusion": "As a result, H2 protected the cultured cells against the cytotoxic effects induced by tert-butyl hydroperoxide; H2 suppressed cellular fatty acid peroxidation and cell membrane permeability, mitigated the decline in mitochondrial oxidoreductase activity and mitochondrial membrane potential, and protected cells against cell death evaluated using propidium iodide staining. These results suggested th" }, { "pmid": "31249254", "year": 2019, "title": "Effects of hydrogen-rich water bath on visceral fat and skin blotch, with boiling-resistant hydrogen bubbles.", "title_en": null, "title_de": "Wirkungen eines Bades in wasserstoffreichem Wasser auf das viszerale Fett und Hautflecken, mit kochbeständigen Wasserstoffbläschen.", "journal": "Medical gas research", "authors": "Asada et al.", "author_search": "asada asada", "doi": "10.4103/2045-9912.260647", "doi_url": "https://doi.org/10.4103/2045-9912.260647", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31249254/", "url": "https://h2medicine.org/studies/study-asada-2019-bath-visceral-fat-skin/", "methods": [ "bath-topical", "drinking-hrw" ], "indications": [ "metabolic", "cardiovascular", "skin-aging", "fundamentals-safety" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2019 · Asada et al. — Effects of hydrogen-rich water bath on visceral fat and skin blotch, with boiling-resistant hydrogen bubbles.", "summary": "Four subjects (2 men, 2 women) bathed daily in H₂-rich warm water (41 °C, ~300 μg/L dissolved H₂) for 1–6 months; the two female subjects showed reduced visceral fat area (47 → 36 cm²) and waist circumference (91 → 82 cm), and all subjects showed reduction of skin blotches — described by the authors as „markedly smaller and thinner“. The study also documents that the H₂ nanobubbles in this water resist boiling. This is an uncontrolled 4-person observational study. (Medical Gas Research, 2019.)", "assessment": "A very small, uncontrolled pilot with an interesting technical finding (H₂ nanobubble stability) and cosmetically relevant but entirely uncontrolled clinical observations. The skin and body composition data in 2–4 people cannot support any claims about efficacy. The unexplained fasting blood glucose increase in one subject is a notable adverse signal that should have been discussed. Limitations: n = 4 total (2 for body composition); no control group; effects of diet, season, and behaviour over 1–6 months cannot be separated; blood glucose anomaly unremarked; the boiling-resistance claim conflicts with established thermodynamics and requires independent replication.", "abstract": "Hydrogen-dissolved water has been shown to improve diverse oxidation stress-related diseases, which drove us to examine effects of hydrogen-rich water on oxidation stress-related skin troubles and lipid-metabolism markers. The purpose of this study is whether the dissolved hydrogen in hydrogen-rich water was kept even after boiling, and whether hydrogen-bath utilization improves cosmetic effects such as skin-blotch repression and the visceral-fat-based slimming effects. The subjects were two men and two women, aged 48, 43, 42, and 41 years (n = 4). They took warm (41°C) water bath of dissolved hydrogen 300-310 μg/L (< 10 μg/L for normal water) for 10-minute once daily for 1-6 months, followed by examination of skin blotch, visceral fat, and cholesterol and glucose metabolisms. The dissolved hydrogen concentration was measured after 15-minute boiling and the subsequent cooling naturally. The wide-ranging, dense, and irregularly shaped skin blotches became markedly smaller and thinner, assumedly through reductive bleaching of melanin and lipofuscin and promotion of dermal cell renewal by the hydrogen-rich warm water. Ultrasonic resonance-based analysis on the abdominal cross-section revealed that the visceral fat area decreased from 47 to 36 cm[2], and the abdominal circumference decreased from 91 to 82 cm, in the two female subjects bathing in hydrogen-water. After 6-month hydrogen-water bathing, the low-density lipoprotein cholesterol level was decreased by 16.2% and the fasting blood glucose level increased by 13.6% in the blood of a female subject. Before boiling, the dissolved hydrogen and an oxidation-reduced potential were 300 μg/L and -115 mV, respectively. Dissolved hydrogen was retained at 300-175 μg/L and 200 μg/L, even 1-6 hours and 24 hours, respectively, after boiling. Therefore, a hydrogen-rich water-bath apparatus can electrolytically generate abundant boiling-resistant hydrogen bubbles, improving visceral fat and blotches on the skin. The study was approved by the Medical Ethics Committee of the Japanese Center for Anti-Aging Medical Sciences and that was officially authenticated by the Hiroshima Prefecture Government of Japan (approval number 15C1) in 2016.", "conclusion": "Therefore, a hydrogen-rich water-bath apparatus can electrolytically generate abundant boiling-resistant hydrogen bubbles, improving visceral fat and blotches on the skin. The study was approved by the Medical Ethics Committee of the Japanese Center for Anti-Aging Medical Sciences and that was officially authenticated by the Hiroshima Prefecture Government of Japan (approval number 15C1) in 2016." }, { "pmid": "31162794", "year": 2019, "title": "Energy conservation in the gut microbe Methanomassiliicoccus luminyensis is based on membrane-bound ferredoxin oxidation coupled to heterodisulfide reduction.", "title_en": null, "title_de": "Energiekonservierung im Darmmikroben Methanomassiliicoccus luminyensis beruht auf membrangebundener Ferredoxin-Oxidation gekoppelt an Heterodisulfid-Reduktion", "journal": "The FEBS journal", "authors": "Kröninger et al.", "author_search": "kröninger kröninger", "doi": "10.1111/febs.14948", "doi_url": "https://doi.org/10.1111/febs.14948", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31162794/", "url": "https://h2medicine.org/studies/study-kroeninger-2019-energy-conservation-gut-microbe/", "methods": [ "unspecified" ], "indications": [ "sports-exercise", "respiratory", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2019 · Kröninger — Energy Conservation in the Gut Microbe Methanomassiliicoccus luminyensis Is Based on Membrane-Bound Ferredoxin Oxidation Coupled to Heterodisulfide Reduction", "summary": "This in-vitro biochemistry study investigates how the gut-derived methanogenic archaeon Methanomassiliicoccus luminyensis generates cellular energy — using molecular hydrogen (H₂) as a reductant to form methane from methylamines. The study reveals a unique energy-conservation pathway not found in other methanogens, using protons rather than sodium ions for energy coupling. This is fundamental microbial biochemistry; it does not test H₂ as a therapeutic agent. (The FEBS Journal, 2019.)", "assessment": "This is rigorous in-vitro microbial biochemistry with no direct therapeutic H₂ relevance. H₂ in this paper is a substrate consumed by a gut microbe — the opposite of therapeutic H₂ supplementation. The study contributes to understanding gut H₂ metabolism and microbiome-level H₂ cycling, which is background context for H₂ medicine but not evidence for any H₂ health effect. No health claims should be derived from this paper.", "abstract": "Methanomassiliicoccus luminyensis was originally isolated from human feces and belongs to the seventh order of methanogens, the Methanomassiliicoccales, which are only distantly related to other methanogenic archaea. The organism forms methane from the reduction of methylamines or methanol using molecular hydrogen as reductant. The energy-conserving system in M. luminyensis is unique and the enzymes involved in this process are not found in this combination in members of the other methanogenic orders. In this context our central question was how the organism is able to generate ATP. Energy transduction was dependent on a membrane-bound ferredoxin: heterodisulfide oxidoreductase composed of reduced ferredoxin as an electron donor, at least one protein in the membrane fraction and the heterodisulfide reductase HdrD, which reduced the electron acceptor CoM-S-S-CoB. Electron transfer of this respiratory chain proceeded with a rate of 145 nmol reduced heterodisulfide min-1 ·mg-1 membrane protein. Methanomassiliicoccus luminyensis is the first example of a methanogenic archaeon that does not require Na+ ions for energy conservation. Only protons were used as coupling ions for the generation of the electrochemical ion gradient. The membrane-bound F420 H2 :phenazine oxidoreductase complex (without the electron input module FpoF) probably catalyzed the oxidation of reduced ferredoxin and potentially acted as primary proton pump in this electron transport system. In summary, the energy-conserving system of M. luminyensis possesses features found in the pathways of hydrogenotrophic and methylotrophic/aceticlastic methanogenesis. Consequently, the composition of the enzymes involved in ion translocation across the cytoplasmic membrane is different from all other methanogenic archaea.", "conclusion": "luminyensis possesses features found in the pathways of hydrogenotrophic and methylotrophic/aceticlastic methanogenesis. Consequently, the composition of the enzymes involved in ion translocation across the cytoplasmic membrane is different from all other methanogenic archaea." }, { "pmid": "31151236", "year": 2019, "title": "Different Molecular Interaction between Collagen and α- or β-Chitin in Mechanically Improved Electrospun Composite.", "title_en": null, "title_de": "Unterschiedliche molekulare Wechselwirkung zwischen Kollagen und α- bzw. β-Chitin in mechanisch verbessertem elektrogesponnenem Komposit", "journal": "Marine drugs", "authors": "Moon et al.", "author_search": "moon moon", "doi": "10.3390/md17060318", "doi_url": "https://doi.org/10.3390/md17060318", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31151236/", "url": "https://h2medicine.org/studies/study-moon-2019-different-interaction-between-collagen/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2019 · Moon — Different Molecular Interaction between Collagen and α- or β-Chitin in Mechanically Improved Electrospun Composite", "summary": "Electrospun composite fibres combining collagen with β-chitin showed 41% higher tensile strength than pure collagen and 14% better than α-chitin composites, due to favourable inter-molecular hydrogen bonds between β-chitin and collagen. This in-vitro materials science study characterises the structural chemistry responsible for the mechanical improvement. Molecular hydrogen here refers to hydrogen bonds in polymer chemistry, not to H₂ gas as a therapeutic agent. (Marine Drugs, 2019.)", "assessment": "This is a materials science / polymer chemistry in-vitro study with no relevance to molecular hydrogen (H₂) therapy. The „hydrogen bonds“ in this paper are standard covalent/non-covalent polymer chemistry — not the dissolved diatomic gas H₂ that is the subject of H₂ medicine research. This paper appears in the database due to keyword overlap. It should not be cited or interpreted in a therapeutic H₂ context.", "abstract": "Although collagens from vertebrates are mainly used in regenerative medicine, the most elusive issue in the collagen-based biomedical scaffolds is its insufficient mechanical strength. To solve this problem, electrospun collagen composites with chitins were prepared and molecular interactions which are the cause of the mechanical improvement in the composites were investigated by two-dimensional correlation spectroscopy (2DCOS). The electrospun collagen is composed of two kinds of polymorphs, α- and β-chitin, showing different mechanical enhancement and molecular interactions due to different inherent configurations in the crystal structure, resulting in solvent and polymer susceptibility. The collagen/α-chitin has two distinctive phases in the composite, but β-chitin composite has a relatively homogeneous phase. The β-chitin composite showed better tensile strength with ~41% and ~14% higher strength compared to collagen and α-chitin composites, respectively, due to a favorable secondary interaction, i.e., inter- rather than intra-molecular hydrogen bonds. The revealed molecular interaction indicates that β-chitin prefers to form inter-molecular hydrogen bonds with collagen by rearranging their uncrumpled crystalline regions, unlike α-chitin.", "conclusion": "The β-chitin composite showed better tensile strength with ~41% and ~14% higher strength compared to collagen and α-chitin composites, respectively, due to a favorable secondary interaction, i.e., inter- rather than intra-molecular hydrogen bonds. The revealed molecular interaction indicates that β-chitin prefers to form inter-molecular hydrogen bonds with collagen by rearranging their uncrumpled " }, { "pmid": "31113492", "year": 2019, "title": "Molecular hydrogen suppresses glioblastoma growth via inducing the glioma stem-like cell differentiation.", "title_en": null, "title_de": "Molekularer Wasserstoff unterdrückt das Glioblastom-Wachstum durch Induktion der Differenzierung gliomstammzellähnlicher Zellen", "journal": "Stem cell research & therapy", "authors": "Liu et al.", "author_search": "liu liu", "doi": "10.1186/s13287-019-1241-x", "doi_url": "https://doi.org/10.1186/s13287-019-1241-x", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31113492/", "url": "https://h2medicine.org/studies/study-liu-2019-suppresses-glioblastoma-growth-inducing/", "methods": [ "inhalation" ], "indications": [ "neurology", "cancer", "skin-aging" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2019 · Liu — Molecular Hydrogen Suppresses Glioblastoma Growth via Inducing the Glioma Stem-Like Cell Differentiation", "summary": "In rat and mouse glioblastoma (GBM) models, daily inhalation of 67% hydrogen gas suppressed tumor growth, prolonged survival, and induced differentiation of cancer stem-like cells — reducing their self-renewal, proliferation, and invasive capacity. The findings suggest that H₂ may work against GBM in part by pushing stem-like cancer cells toward a more differentiated, less aggressive state. These are animal and cell-culture results; human clinical applicability requires further investigation. (Stem Cell Research and Therapy, 2019.)", "assessment": "An interesting animal study exploring a novel mechanism (CSC differentiation) by which H₂ might act against GBM. The multi-model approach (orthotopic rat + subcutaneous mouse + in-vitro) adds robustness. Honest limitations: (1) animal GBM models do not recapitulate the full complexity of human glioblastoma; (2) 67% H₂ inhalation is not a consumer-accessible intervention and carries safety considerations at such concentrations; (3) no human data exist; (4) survival benefit, while shown, is in an experimental transplant model — not reflective of the multifactorial human disease course. This is hypothesis-generating preclinical research that warrants further investigation but should not be presented as evidence of efficacy in human GBM patients.", "abstract": "BACKGROUND: Glioblastoma (GBM) is the most common type of primary malignant brain tumor. Molecular hydrogen has been considered a preventive and therapeutic medical gas in many diseases including cancer. In our study, we sought to assess the potential role of molecular hydrogen on GBM. METHODS: The in vivo studies were performed using a rat orthotopic glioma model and a mouse subcutaneous xenograft model. Animals inhaled hydrogen gas (67%) 1 h two times per day. MR imaging studies were performed to determine the tumor volume. Immunohistochemistry (IHC), immunofluorescence staining, and flow cytometry analysis were conducted to determine the expression of surface markers. Sphere formation assay was performed to assess the cancer stem cell self-renewal capacity. Assays for cell migration, invasion, and colony formation were conducted. RESULTS: The in vivo study showed that hydrogen inhalation could effectively suppress GBM tumor growth and prolong the survival of mice with GBM. IHC and immunofluorescence staining demonstrated that hydrogen treatment markedly downregulated the expression of markers involved in stemness (CD133, Nestin), proliferation (ki67), and angiogenesis (CD34) and also upregulated GFAP expression, a marker of differentiation. Similar results were obtained in the in vitro studies. The sphere-forming ability of glioma cells was also suppressed by hydrogen treatment. Moreover, hydrogen treatment also suppressed the migration, invasion, and colony-forming ability of glioma cells. CONCLUSIONS: Together, these results indicated that molecular hydrogen may serve as a potential anti-tumor agent in the treatment of GBM.", "conclusion": "Together, these results indicated that molecular hydrogen may serve as a potential anti-tumor agent in the treatment of GBM." }, { "pmid": "31083022", "year": 2019, "title": "Hydrogen gas protects against ovariectomy-induced osteoporosis by inhibiting NF-κB activation.", "title_en": null, "title_de": "Wasserstoffgas schützt vor ovariektomie-induzierter Osteoporose durch Hemmung der NF-κB-Aktivierung.", "journal": "Menopause (New York, N.Y.)", "authors": "Wu et al.", "author_search": "wu wu", "doi": "10.1097/gme.0000000000001310", "doi_url": "https://doi.org/10.1097/gme.0000000000001310", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31083022/", "url": "https://h2medicine.org/studies/study-wu-2019-protects-against-ovariectomy-induced/", "methods": [ "inhalation" ], "indications": [ "cancer", "joints-rheumatology", "immune-system", "womens-health" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2019 · Wu — Hydrogen gas protects against ovariectomy-induced osteoporosis by inhibiting NF-κB activation.", "summary": "In mice with surgically induced estrogen deficiency (ovariectomy model of postmenopausal osteoporosis), inhalation of 60 % molecular hydrogen (H₂) markedly reduced bone loss. Trabecular bone density rose by more than 40 % and pro-inflammatory cytokines fell by more than 50 % compared to untreated ovariectomized animals. The proposed mechanism runs through inhibition of the NF-κB signaling pathway, which drives osteoclast differentiation. (Menopause, 2019.)", "assessment": "An interesting mechanistic animal study, but not a proof of efficacy in humans. The results are derived entirely from a mouse model and cell culture — no human subjects were included. The H₂ concentration used (60 %) is a pharmacological dose in an experimental setting that cannot be translated directly to practical human application. NF-κB inhibition as a mechanism is plausible and supported by other H₂ literature, but clinical translation requires dose-finding, safety data, and controlled trials in postmenopausal women. The authors' conclusion that „H₂ could be an effective therapeutic agent” is a hypothesis, not an established fact.", "abstract": "OBJECTIVES: Osteoporosis is a prevalent condition among postmenopausal women, and lacks satisfactory therapeutic options. Hydrogen (H2) has been shown to be effective in alleviating many diseases. This study aimed to investigate the effects of H2 on inhibiting osteoclastogenesis and bone loss in ovariectomized mice. METHODS: Osteoclast differentiation from Raw264.7 cells was induced with receptor activator NF-κB ligand (RANKL) with or without 60% H2. The number and resorption activity of osteocalsts were assessed by tartrate-resistant acid phosphatase staining and pit formation assay, respectively. The expression of osteoclast markers and NF-κB phosphorylation were detected by western blot. NF-κB nuclear translocation was assessed by immunofluorescence. NF-κB transcriptional activity was analyzed by luciferase assay. Bone loss in mice was induced by ovariectomy (OVX). OVX mice were given either regular air or 60% H2. Bone structure was analyzed by micro-computed tomography and hematoxylin and eosin staining. Cytokine levels were measured by enzyme-linked immunosorbent assay. The data were analyzed with one-way or two-way ANOVA followed by Bonferroni post hoc tests. RESULTS: H2 did not have any measurable effect on the proliferation of Raw264.7 cells. The number of osteoclasts and size of resorption pits of RANKL+H2-treated cells were 3 to 4 times less than RANKL treated cells. The expression of osteoclast marker genes of RANKL+H2-treated cells was 30% to 60% lower than RANKL-treated cells (P < 0.05). H2 markedly inhibited RANKL-induced activation, nuclear translocation, and transcriptional activity of NF-κB (P < 0.05, RANKL+H2 vs RANKL). The amount and density of trabecular bone and bone mineral density of ovariectomized mice were significantly less than sham-operated mice (P < 0.05 OVX vs sham). The amount of trabecular bone and bone mineral density of OVX mice that inhaled H2 were more than 40% higher, whereas the levels of serum proinflammatory cytokine interleukin 1β, IL-6, and tumor necrosis factor-α were more than 50% lower than those of OVX mice (P < 0.05). CONCLUSIONS: These results demonstrated that H2 could be an effective therapeutic agent of postmenopausal osteoporosis.", "conclusion": "These results demonstrated that H2 could be an effective therapeutic agent of postmenopausal osteoporosis." }, { "pmid": "31013316", "year": 2019, "title": "Effects of hydrogen-rich water in a rat model of polycystic kidney disease.", "title_en": null, "title_de": "Wirkungen von wasserstoffreichem Wasser in einem Rattenmodell der polyzystischen Nierenerkrankung.", "journal": "PloS one", "authors": "Yamasaki et al.", "author_search": "yamasaki yamasaki", "doi": "10.1371/journal.pone.0215766", "doi_url": "https://doi.org/10.1371/journal.pone.0215766", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/31013316/", "url": "https://h2medicine.org/studies/study-yamasaki-2019-rat-model-polycystic-kidney/", "methods": [ "drinking-hrw" ], "indications": [ "metabolic", "kidney-dialysis", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2019 · Yamasaki — Effects of hydrogen-rich water in a rat model of polycystic kidney disease.", "summary": "In PCK rats — a rodent model of polycystic kidney disease — drinking hydrogen-rich water did not significantly reduce cyst growth compared to plain water when consumed in equivalent volumes. High-volume fluid intake (regardless of H₂ content) slightly reduced kidney-to-body-weight ratio, but H₂ showed no additional benefit over water alone in this experimental design. The authors suggest that altered delivery method or duration might yield different results. (PLOS ONE, 2019.)", "assessment": "This animal study should be read as a caution against over-generalizing positive H₂ findings to polycystic kidney disease. The result is a null finding for H₂-specific cyst suppression in this specific rodent model. No human data exist for this application. The study is small (n = 40 rats, 10 per group) and short (10 weeks). The null result does not conclusively disprove an effect — design limitations (dose, timing, route) leave room for future study — but it does demonstrate that H₂ is not universally effective in every oxidative-stress-related disease model.", "abstract": "Various factors are considered to be mechanisms of the increase in the sizes of cysts in patients with polycystic kidney disease. Vasopressin is one of the causes, and drinking large volumes of water shows an effect of suppressing an increase in cysts. On the other hand, it is known that hydrogen-rich water reduces oxidative stress and has a good effect on kidney injury. We examined whether drinking large volumes of hydrogen-rich water affected the increase in the sizes of cysts. Forty 5-week-old PCK rats were randomly assigned to four groups: C(Control), purified water; W(Water), water with sugar; H(Hydrogen), hydrogen-rich water; WH(Water+Hydrogen), hydrogen-rich water with sugar. They consumed water from 5 to 15 weeks of age. The intake of water in the groups in which sugar was added to the water (W, WH) significantly increased in comparison to C, but there was no significant change in the serum Creatinine concentration. The kidney weight per body weight in W was significantly decreased in comparison to C. The kidney weights in H and WH were significantly increased in comparison to W. There were no significant differences in the ratio of the cross-sectional area of the cysts to the whole area among the groups. This experiment showed that the effect of drinking large volumes of hydrogen-rich water was not significantly different from that of normal water, in terms of preventing an increase in the size of cysts in PCK rats. However, some papers acknowledge the influence of hydrogen water. Significant differences might become obvious if we change aspects such as the administration method or administration period.", "conclusion": "However, some papers acknowledge the influence of hydrogen water. Significant differences might become obvious if we change aspects such as the administration method or administration period." }, { "pmid": "30968583", "year": 2019, "title": "Acid-Responsive H2 -Releasing 2D MgB2 Nanosheet for Therapeutic Synergy and Side Effect Attenuation of Gastric Cancer Chemotherapy.", "title_en": null, "title_de": "Säureempfindliches H₂-freisetzendes 2D-MgB₂-Nanoblatt für therapeutische Synergie und Abschwächung von Nebenwirkungen der Magenkrebs-Chemotherapie.", "journal": "Advanced healthcare materials", "authors": "Fan et al.", "author_search": "fan fan", "doi": "10.1002/adhm.201900157", "doi_url": "https://doi.org/10.1002/adhm.201900157", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/30968583/", "url": "https://h2medicine.org/studies/study-fan-2019-acid-responsive-releasing-mgb2/", "methods": [ "saline-iv", "drinking-hrw" ], "indications": [ "liver", "sports-exercise", "cancer" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2019 · Fan — Acid-Responsive H₂-Releasing 2D MgB₂ Nanosheet for Therapeutic Synergy and Side Effect Attenuation of Gastric Cancer Chemotherapy.", "summary": "Researchers engineered a magnesium boride (MgB₂) nanosheet that releases molecular hydrogen in acidic environments (such as the stomach) and combined it with the chemotherapy drug doxorubicin in a gastric-tumor mouse model. The combined „hydrogenochemotherapy” significantly prolonged survival compared to chemotherapy alone, while reducing toxic side effects to bone marrow, heart, liver, and spleen. The proposed mechanism is that H₂ selectively inhibits aerobic respiration in cancer cells while protecting normal tissue. (Advanced Healthcare Materials, 2019.)", "assessment": "A preclinical proof-of-concept study — not a clinical finding. All results are from a mouse gastric-cancer xenograft model; no human patients were involved. The nano-delivery system is inventive, but its clinical feasibility — manufacturing, regulatory approval, long-term safety, bioavailability — remains entirely unproven. The proposed mechanism of selective inhibition of cancer-cell aerobic respiration by H₂ is a fascinating hypothesis that requires much further validation. This paper contributes to the mechanistic understanding of H₂ in oncology but should not be interpreted as evidence of efficacy in human cancer treatment.", "abstract": "The hydrogen molecule is recognized as a high potential to attenuate toxic side effects of chemotherapy and also enhance chemotherapeutic efficacy, and the development of a novel hydrogen-generating prodrug for facile, safe, and efficient hydrogen delivery is vitally important for combined hydrogenochemotherapy but is still challenging. Here, targeting gastric cancer, a 2D magnesium boride nanosheet (MBN) is synthesized as a new type of acid-responsive hydrogen-releasing prodrug by an ultrasound-assisted chemical etching route, which is used to realize hydrogenochemotherapy by combination of facile oral administration of polyvinylpyrrolidone (PVP)-encapsulating MBN (MBN@PVP) pills with routine intravenous injection of doxorubicin (DOX). The MBN@PVP pill has high stability in normal tissues/blood environments as well as high gastric acid-responsiveness with sustained release behavior, which matches well with its metabolism rate in the stomach in great favor of continuous and long-term hydrogen administration. Hydrogenochemotherapy with DOX+MBN@PVP has remarkably prolonged the survival time of gastric tumor-bearing mice by reducing the toxic side effects of chemotherapy. The mechanism for therapeutic synergy and side effect attenuation of hydrogenochemotherapy is discovered to be derived from the selectivity of hydrogen molecules in inhibiting aerobic respiration of gastric cells but activating aerobic respiration of normal cells including marrow mesenchymal stem cells and cardiac, hepatic, and splenic cells.", "conclusion": "Hydrogenochemotherapy with DOX+MBN@PVP has remarkably prolonged the survival time of gastric tumor-bearing mice by reducing the toxic side effects of chemotherapy. The mechanism for therapeutic synergy and side effect attenuation of hydrogenochemotherapy is discovered to be derived from the selectivity of hydrogen molecules in inhibiting aerobic respiration of gastric cells but activating aerobic " }, { "pmid": "30877875", "year": 2019, "title": "Hydrogen gas inhalation attenuates sepsis-induced liver injury in a FUNDC1-dependent manner.", "title_en": null, "title_de": "Wasserstoffgas-Inhalation mildert die sepsis-induzierte Leberschädigung in FUNDC1-abhängiger Weise.", "journal": "International immunopharmacology", "authors": "Yan et al.", "author_search": "yan yan", "doi": "10.1016/j.intimp.2019.03.021", "doi_url": "https://doi.org/10.1016/j.intimp.2019.03.021", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/30877875/", "url": "https://h2medicine.org/studies/study-yan-2019-inhalation-attenuates-sepsis-induced/", "methods": [ "inhalation", "saline-iv" ], "indications": [ "liver", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2019 · Yan — Hydrogen gas inhalation attenuates sepsis-induced liver injury in a FUNDC1-dependent manner.", "summary": "In septic mice (cecal ligation and puncture model), 2 % hydrogen (H₂) gas inhalation for 3 hours improved the 7-day survival rate and reduced markers of liver damage. The protective mechanism appears to depend on the mitophagy receptor FUNDC1: when FUNDC1 was pharmacologically blocked, H₂ lost its protective effect. This identifies a specific molecular pathway through which H₂ may protect liver cells during sepsis. (International Immunopharmacology, 2019.)", "assessment": "This is a well-designed preclinical mechanistic study in mice — not clinical evidence for humans. It advances the mechanistic understanding of how H₂ might protect against septic liver injury via FUNDC1-dependent mitophagy, which is a meaningful scientific contribution. However, all findings are in male mice using a specific surgical sepsis model; no human patients were studied. The clinical gap — including dosing, delivery in ICU settings, and patient heterogeneity — is substantial. Results should not be extrapolated to human sepsis management.", "abstract": "Sepsis-induced hepatic dysfunction is considered as an independent risk factor of multiple organ dysfunction syndrome (MODS) and death. Mitophagy, a selective form of autophagy, plays a major role in sepsis-induced organ damage. We have demonstrated that hydrogen gas (H2), a selective antioxidant, exerts protective effects in septic mice. Here, we hypothesize that the therapeutic effects of H2 on septic animals with liver damages may be exerted through regulation of the Fun14 domain-containing protein 1 (FUDNC1)-induced mitophagy pathway. Male C57BL/6J mice were subjected to sham or cecal ligation and puncture (CLP) operation and treated with 2% H2 gas inhalation for 3 h starting at 1 h after sham or CLP surgery. To verify the role of FUNDC1, the cell-penetrating peptide P (NH2-GRKKRRQRRRPQDYESDDESYEVLDLTEY-COOH) (1 mg/kg) that functions as a FUNDC1 inhibitor was intraperitoneally injected into mice 24 h before the sham or CLP operation. To evaluate the severity of septic liver injury, the 7-day survival rate, liver histopathologic score, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, respiration control ratio (RCR), and FUDNC1, P-18-FUDNC1, P62, LC3B-II, Tim23, and caspase-1 levels were evaluated after the sham or CLP operation. The results demonstrated that 2% H2 gas inhalation resulted in an increase in the 7-day survival rate, ALT and AST levels, RCR, and P62 and LC3B-II expression but decreased the histological score and FUDNC1, P-18-FUDNC1, Tim23, and caspase-1 levels after sepsis. However, no significant differences were reported between the CLP + peptide P and CLP + H2 + peptide P groups. These observations indicate that 2% H2 gas inhalation for 3 h may serve as an effective therapeutic strategy for sepsis-induced liver injury through the regulation of FUNDC1-dependent mitophagy.", "conclusion": "However, no significant differences were reported between the CLP + peptide P and CLP + H2 + peptide P groups. These observations indicate that 2% H2 gas inhalation for 3 h may serve as an effective therapeutic strategy for sepsis-induced liver injury through the regulation of FUNDC1-dependent mitophagy." }, { "pmid": "30858437", "year": 2019, "title": "Hydrogen ventilation combined with mild hypothermia improves short-term neurological outcomes in a 5-day neonatal hypoxia-ischaemia piglet model.", "title_en": null, "title_de": "Wasserstoff-Beatmung kombiniert mit milder Hypothermie verbessert kurzfristige neurologische Ergebnisse in einem 5-Tage-Ferkelmodell der neonatalen Hypoxie-Ischämie.", "journal": "Scientific reports", "authors": "Htun et al.", "author_search": "htun htun", "doi": "10.1038/s41598-019-40674-8", "doi_url": "https://doi.org/10.1038/s41598-019-40674-8", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/30858437/", "url": "https://h2medicine.org/studies/study-htun-2019-ventilation-combined-mild-hypothermia/", "methods": [ "unspecified" ], "indications": [ "sports-exercise", "neurology", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2019 · Htun — Hydrogen ventilation combined with mild hypothermia improves short-term neurological outcomes in a 5-day neonatal hypoxia-ischaemia piglet model.", "summary": "In newborn piglets that had suffered hypoxic-ischaemic brain injury (a model for birth asphyxia), combining therapeutic hypothermia with hydrogen (H₂) ventilation produced better neurological recovery scores than hypothermia alone over 5 days. The H₂+hypothermia group also showed a trend toward improved cortical and white-matter histology and less cell death. These findings suggest H₂ may add benefit on top of the current standard of care for neonatal hypoxic-ischaemic encephalopathy — but in a piglet model only. (Scientific Reports, 2019.)", "assessment": "A preclinical piglet study — promising but far from clinical evidence. The piglet model is more translatable to human neonates than rodent models, which gives these findings somewhat greater translational weight. However, the study is small, short, and does not address long-term neurodevelopmental outcomes. No human neonates were studied. Therapeutic hypothermia combined with H₂ ventilation would require dedicated neonatal clinical trials before any application can be considered. The result is a meaningful signal for further research, not a treatment recommendation.", "abstract": "Despite its poor outcomes, therapeutic hypothermia (TH) is the current standard treatment for neonatal hypoxic-ischaemic encephalopathy (HIE). In this study, due to its antioxidant, anti-inflammatory, and antiapoptotic properties, the effectiveness of molecular hydrogen (H2) combined with TH was evaluated by means of neurological and histological assessments. Piglets were divided into three groups: hypoxic-ischaemic insult with normothermia (NT), insult with hypothermia (TH, 33.5 ± 0.5 °C), and insult with hypothermia with H2 ventilation (TH-H2, 2.1-2.7%). H2 ventilation and TH were administered for 24 h. After ventilator weaning, neurological assessment was performed every 6 h for 5 days. On day 5, the brains of the piglets were harvested for histopathological analysis. Regarding the neurological score, the piglets in the TH-H2 group consistently had the highest score from day 2 to 5 and showed a significantly higher neurological score from day 3 compared with the NT group. Most piglets in the TH-H2 group could walk at day 3 of recovery, whereas walking ability was delayed in the two other groups. The histological results revealed that TH-H2 tended to improve the status of cortical gray matter and subcortical white matter, with a considerable reduction in cell death. In this study, the combination of TH and H2 improved short-term neurological outcomes in neonatal hypoxic-ischaemic piglets.", "conclusion": "The histological results revealed that TH-H2 tended to improve the status of cortical gray matter and subcortical white matter, with a considerable reduction in cell death. In this study, the combination of TH and H2 improved short-term neurological outcomes in neonatal hypoxic-ischaemic piglets." }, { "pmid": "30853611", "year": 2019, "title": "In vitro and in vivo studies of Mg-30Sc alloys with different phase structure for potential usage within bone.", "title_en": null, "title_de": "In-vitro- und In-vivo-Studien zu Mg-30Sc-Legierungen mit unterschiedlicher Phasenstruktur für die mögliche Anwendung im Knochen.", "journal": "Acta biomaterialia", "authors": "Liu et al.", "author_search": "liu liu", "doi": "10.1016/j.actbio.2019.03.009", "doi_url": "https://doi.org/10.1016/j.actbio.2019.03.009", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/30853611/", "url": "https://h2medicine.org/studies/study-liu-2019-vitro-vivo-30sc-alloys/", "methods": [ "inhalation" ], "indications": [ "liver", "sports-exercise", "neurology", "kidney-dialysis", "immune-system" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2019 · Liu — In vitro and in vivo studies of Mg-30Sc alloys with different phase structure for potential usage within bone.", "summary": "Researchers developed a magnesium-scandium (Mg-30Sc) alloy with a body-centred-cubic (bcc) crystal structure as a biodegradable orthopaedic implant material and tested it in cell cultures and rats over 24 weeks. The β-phase bcc alloy showed superior mechanical strength (>600 MPa compressive strength), low in-vivo corrosion rate, no cytotoxicity, and good bone integration — with only limited hydrogen gas release during degradation. (Acta Biomaterialia, 2019.)", "assessment": "This is a preclinical biomaterials study, not a study of therapeutic H₂. The H₂ aspect is specifically about minimizing incidental H₂ gas release from a degradable implant — the goal is to keep H₂ low, not to administer it therapeutically. Results are from cell culture and a rat femur model; no human implantation data exist. The alloy concept is scientifically interesting but far from clinical application. This paper is not evidence for therapeutic H₂ in any sense — it belongs to implant materials science.", "abstract": "Proper alloying magnesium with element scandium (Sc) could transform its microstructure from α phase with hexagonal closed-packed (hcp) structure into β phase with body-cubic centered (bcc) structure. In the present work, the Mg-30 wt% Sc alloy with single α phase, dual phases (α + β) or β phase microstructure were developed by altering the heat-treatment routines and their suitability for usage within bone was comprehensively investigated. The β phased Mg-30 wt% Sc alloy showed the best mechanical performance with ultimate compressive strength of 603 ± 39 MPa and compressive strain of 31 ± 3%. In vitro degradation test showed that element scandium could effectively incorporate into the surface corrosion product layer, form a double-layered structure, and further protect the alloy matrix. No cytotoxic effect was observed for both single α phased and β phased Mg-30 wt% Sc alloys on MC3T3 cell line. Moreover, the β phased Mg-30 wt%Sc alloy displayed acceptable corrosion resistance in vivo (0.06 mm y-1) and maintained mechanical integrity up to 24 weeks. The degradation process did not significantly influence the hematology indexes of inflammation, hepatic or renal functions. The bone-implant contact ratio of 75 ± 10% after 24 weeks implied satisfactory integration between β phased Mg-30 wt%Sc alloy and the surrounding bone. These findings indicate a potential usage of the bcc-structured Mg-Sc alloy within bone and might provide a new strategy for future biomedical magnesium alloy design. STATEMENT OF SIGNIFICANCE: Scandium is the only rare earth element that can transform the matrix of magnesium alloy into bcc structure, and Mg-30 wt%Sc alloy had been recently reported to exhibit shape memory effect. The aim of the present work is to study the feasibility of Mg-30 wt%Sc alloy with different constitutional phases (single α phase, single β phase or dual phases (α + β)) as biodegradable orthopedic implant by in vitro and in vivo testings. Our findings showed that β phased Mg-30 wt%Sc alloy which is of bcc structure exhibited improved strength and superior in vivo degradation performance (0.06 mm y-1). No cytotoxicity and systematic toxicity were shown for β phased Mg-30 wt%Sc alloy on MC3T3 cell model and rat organisms. Moreover, good osseointegration, limited hydrogen gas release and maintained mechanical integrity were observed after 24 weeks' implantation into the rat femur bone.", "conclusion": "No cytotoxicity and systematic toxicity were shown for β phased Mg-30 wt%Sc alloy on MC3T3 cell model and rat organisms. Moreover, good osseointegration, limited hydrogen gas release and maintained mechanical integrity were observed after 24 weeks' implantation into the rat femur bone." }, { "pmid": "30825755", "year": 2019, "title": "Hyperoxygenated Hydrogen-Rich Solution Suppresses Lung Injury Induced by Hemorrhagic Shock in Rats.", "title_en": null, "title_de": "Hyperoxygenierte wasserstoffreiche Lösung unterdrückt die durch hämorrhagischen Schock induzierte Lungenschädigung bei Ratten.", "journal": "The Journal of surgical research", "authors": "Meng et al.", "author_search": "meng meng", "doi": "10.1016/j.jss.2019.01.050", "doi_url": "https://doi.org/10.1016/j.jss.2019.01.050", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/30825755/", "url": "https://h2medicine.org/studies/study-meng-2019-hyperoxygenated-solution-suppresses-lung/", "methods": [ "bath-topical" ], "indications": [ "cardiovascular", "respiratory", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2019 · Meng — Hyperoxygenated Hydrogen-Rich Solution Suppresses Lung Injury Induced by Hemorrhagic Shock in Rats.", "summary": "In rats with hemorrhagic-shock-induced acute lung injury (ALI), intravenous infusion of a solution combining both extra oxygen and dissolved hydrogen (HOHS) outperformed standard resuscitation fluid and each component alone in protecting lung tissue. HOHS significantly reduced oxidative stress markers, inflammatory cytokines, and cell death in lung tissue. This rodent study suggests a synergistic benefit of combining both gases in a resuscitation fluid. (The Journal of Surgical Research, 2019.)", "assessment": "A well-designed preclinical rat study with a logical four-arm comparison — not clinical evidence. All animals were male rats under a highly controlled hemorrhagic shock protocol; no human data exist for this specific formulation. The practical challenges of manufacturing, stabilizing, and clinically deploying a solution with both elevated dissolved O₂ and H₂ are not addressed. The results are promising as a concept but need larger animal studies and eventually clinical trials before any conclusions about human benefit can be drawn.", "abstract": "BACKGROUND: Hemorrhagic shock could induce acute lung injury (ALI), which is associated with cell hypoxia, lung tissue inflammation, free radical damage, and excessive cell apoptosis. Our previous studies demonstrated that hyperoxygenated solution could alleviate cell hypoxia. Furthermore, hydrogen-rich solution (HS) could relieve lung tissue inflammation, free radical damage and excessive cell apoptosis. Therefore we hypothesize that Hyperoxygenated Hydrogen-rich solution (HOHS) can protect the lung against ALI. MATERIALS AND METHODS: SD rats were randomly divided into five groups (n = 6 at each time point in each group) and were exposed to Hemorrhagic shock induced ALI, and then treated with lactated Ringer's solution (LRS), hyperoxygenated solution, HS, and HOHS, respectively. The protective effects of these solutions were assessed using methods as follows: arterial blood samples were collected for blood gas analysis; Bronchoalveolar lavage fluid was collected for cell count and protein quantification; lung tissue samples were collected to measure wet/dry ratio, as well as levels of T-SOD, MDA, TNF-α, and IL-6; Caspase-3 and TUNEL-positive cells, and pathological changes were observed under light microscope; ALI was scored using the Smith scoring method; ultrastructural changes of lung tissues were further observed with transmission electron microscopy. RESULTS: The results indicated that PaO2, PaCO2, and T-SOD increased in the three treatment groups (P < 0.05), most significantly in the HOHS group (P < 0.01) compared with the LRS group; and conversely that the levels of lactate, MDA, TNF-α and IL-6, cell count, protein content, caspase-3 and TUNEL-positive cells as well as ALI score decreased in the three treatment groups (P < 0.05), most significantly in the HOHS group (P < 0.01) compared with the LRS group. Morphological observation with optical microscope and electron microscopy showed that compared with the LRS group, cell damage in the three treatment groups improved to a varying extent, especially evident in the HOHS group. CONCLUSIONS: These findings demonstrate that HOHS can protect the lung against ALI induced by hemorrhagic shock.", "conclusion": "These findings demonstrate that HOHS can protect the lung against ALI induced by hemorrhagic shock." }, { "pmid": "30693753", "year": 2019, "title": "Mechanical Strength, Biodegradation, and in Vitro and in Vivo Biocompatibility of Zn Biomaterials.", "title_en": null, "title_de": "Mechanische Festigkeit, Bioabbaubarkeit sowie In-vitro- und In-vivo-Biokompatibilität von Zn-Biomaterialien.", "journal": "ACS applied materials & interfaces", "authors": "Zhu et al.", "author_search": "zhu zhu", "doi": "10.1021/acsami.8b20634", "doi_url": "https://doi.org/10.1021/acsami.8b20634", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/30693753/", "url": "https://h2medicine.org/studies/study-zhu-2019-mechanical-strength-biodegradation-vitro/", "methods": [ "inhalation" ], "indications": [ "cardiovascular", "immune-system" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2019 · Zhu — Mechanical Strength, Biodegradation, and in Vitro and in Vivo Biocompatibility of Zn Biomaterials.", "summary": "Zinc (Zn)-based alloys were evaluated as a new class of biodegradable metal implant materials — notable specifically because they degrade without producing hydrogen gas, unlike magnesium-based implants. Alloying Zn with small amounts of Sr or Mg significantly improved mechanical strength, while corrosion rate, cytotoxicity, and in-vivo immune response remained acceptable in cell culture and animal testing. (ACS Applied Materials & Interfaces, 2019.)", "assessment": "This is a preclinical biomaterials study — not a therapeutic H₂ study. The H₂ connection is that Zn implants are positioned as superior to Mg implants precisely because they avoid H₂ gas release. The study is in-vitro and early-phase in-vivo; no human implantation data exist. It does not contribute evidence for or against therapeutic molecular H₂ — it is implant materials science with a note about H₂ as an unwanted by-product in the competing technology.", "abstract": "Zn-based biomaterials have emerged as promising new types of bioresorbable metallics applicable to orthopedic devices, cardiovascular stents, and other medical applications recently. Compared to other degradable metallic biomaterials (i.e., Mg- or Fe-based), Zn biomaterials have a more appropriate corrosion rate without hydrogen gas evolution. Here, we evaluated the potential of Zn-based metallics as medical implants, both in vitro and in vivo, alongside a standard benchmark Mg alloy, AZ31. The mechanical properties of the pure Zn were not strong enough but were significantly enhanced (microhardness > 70 kg/mm2, strength > 220 MPa, elongation > 15%) after alloying with Sr or Mg (1.5 at. %), surpassing the minimal design criteria for load-bearing device applications. The corrosion rate of Zn-based biomaterials was about 0.4 mm/year, significantly slower than that of AZ31. The measured cell viability and proliferation of three different human primary cells fared better for Zn-based biomaterials than AZ31 using both direct and indirect culture methods. Platelet adhesion and activation on Zn-based materials were minimal, significantly less than on AZ31. The hemolysis ratio of red cells (<0.5%) after incubation with Zn-based materials was also well below the ISO standard of 5%. Moreover, Zn-based biomaterials promoted stem cell differentiation to induce the extracellular matrix mineralization process. In addition, in vivo animal testing using subcutaneous, bone, and vascular implantations revealed that the acute toxicity and immune response of Zn-based biomaterials were minimal/moderate, comparable to that of AZ31. No extensive cell death and foreign body reactions were observed. Taken together, Zn-based biomaterials may have a great potential as promising candidates for medical implants.", "conclusion": "No extensive cell death and foreign body reactions were observed. Taken together, Zn-based biomaterials may have a great potential as promising candidates for medical implants." }, { "pmid": "30660872", "year": 2019, "title": "Hydrogen gas reduces HMGB1 release in lung tissues of septic mice in an Nrf2/HO-1-dependent pathway.", "title_en": null, "title_de": "Wasserstoffgas reduziert die HMGB1-Freisetzung im Lungengewebe septischer Mäuse über einen Nrf2/HO-1-abhängigen Signalweg.", "journal": "International immunopharmacology", "authors": "Yu et al.", "author_search": "yu yu", "doi": "10.1016/j.intimp.2019.01.022", "doi_url": "https://doi.org/10.1016/j.intimp.2019.01.022", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/30660872/", "url": "https://h2medicine.org/studies/study-yu-2019-reduces-hmgb1-release-lung/", "methods": [ "inhalation" ], "indications": [ "cancer", "respiratory", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2019 · Yu — Hydrogen gas reduces HMGB1 release in lung tissues of septic mice in an Nrf2/HO-1-dependent pathway.", "summary": "In septic mice (CLP model), 2 % hydrogen (H₂) gas inhalation reduced lung injury, improved survival, and decreased the release of HMGB1 — a late-phase danger signal in sepsis — through a pathway requiring the Nrf2 transcription factor and the enzyme HO-1. When Nrf2 was genetically knocked out, H₂ lost its protective effects, confirming the Nrf2/HO-1 axis as essential to H₂'s mechanism of action in this model. (International Immunopharmacology, 2019.)", "assessment": "A mechanistically rigorous preclinical animal study — not clinical evidence for humans. The use of Nrf2 knockout mice to establish pathway dependency is a strength. However, the entire dataset is from a single species (male ICR mice), a specific surgical sepsis model, and a fixed H₂ inhalation protocol that may not be clinically achievable. HMGB1 suppression through Nrf2/HO-1 is a promising mechanistic pathway, but no H₂ study has yet shown benefit in human sepsis. Results should not be extrapolated beyond the animal model.", "abstract": "BACKGROUND: Lung injury is a vital contributor of mortality in septic patients. Our previous studies have found that molecular hydrogen (H2), which has anti-oxidant, anti-inflammatory, and anti-apoptosis effects, had a therapeutic effect on a septic animal model through increasing expression of nuclear factor-erythroid 2-related factor 2 (Nrf2). The aim of this research was to investigate the effects of 2% H2 gas inhalation on sepsis-induced lung injury and its underlying mechanisms. METHODS: Male wild-type (WT) and Nrf2-knockout (Nrf2-KO) ICR mice underwent sham or cecal ligation and puncture (CLP) operation. Two percent of H2 gas was inhaled for 60 min beginning at both 1 h and 6 h after sham or CLP surgery. To assess the severity of septic lung injury, the 7-day survival rate, wet/dry (W/D) weight ratio of lung tissue, lung histopathologic score, pro-inflammatory cytokines (tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), high-mobility group box 1 (HMGB1)), anti-inflammatory cytokine (interleukin 10 (IL-10)), antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), and heme oxygenase 1 (HO-1)), and an oxidative product (malondialdehyde (MDA)) were detected after sham or CLP operation. The histopathologic changes were observed in lung tissues by hematoxylin and eosin (HE) staining, and pro-inflammatory cytokines (TNF-α and IL-6), anti-inflammatory cytokine (IL-10), antioxidant enzymes (SOD and CAT), and MDA were detected in lung tissues by an enzyme-linked immunosorbent assay (ELISA). RESULTS: The results indicated that 2% H2 gas treatment increased the survival rates, decreased the W/D weight ratio and the lung injury score, alleviated the injuries caused by oxidative stress and inflammation, and induced HO-1 level but reduced HMGB1 level in WT but not Krf2-KO mice. These data reveal that H2 gas could suppress lung injury in septic mice through regulation of HO-1 and HMGB1 expression and that Nrf2 plays a main role in the protective effects of H2 gas on lung damage caused by sepsis.", "conclusion": "RESULTS: The results indicated that 2% H2 gas treatment increased the survival rates, decreased the W/D weight ratio and the lung injury score, alleviated the injuries caused by oxidative stress and inflammation, and induced HO-1 level but reduced HMGB1 level in WT but not Krf2-KO mice. These data reveal that H2 gas could suppress lung injury in septic mice through regulation of HO-1 and HMGB1 exp" }, { "pmid": "30259991", "year": 2019, "title": "Hydrogen gas reduces chronic intermittent hypoxia-induced hypertension by inhibiting sympathetic nerve activity and increasing vasodilator responses via the antioxidation.", "title_en": null, "title_de": "Wasserstoffgas reduziert die durch chronische intermittierende Hypoxie induzierte Hypertonie durch Hemmung der sympathischen Nervenaktivität und Steigerung vasodilatatorischer Reaktionen über die Antioxidation.", "journal": "Journal of cellular biochemistry", "authors": "Guan et al.", "author_search": "guan guan", "doi": "10.1002/jcb.27684", "doi_url": "https://doi.org/10.1002/jcb.27684", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/30259991/", "url": "https://h2medicine.org/studies/study-guan-2019-reduces-chronic-intermittent-hypoxia/", "methods": [ "inhalation" ], "indications": [ "cardiovascular", "kidney-dialysis", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2019 · Guan — Hydrogen gas reduces chronic intermittent hypoxia-induced hypertension by inhibiting sympathetic nerve activity and increasing vasodilator responses via antioxidation.", "summary": "In rats subjected to chronic intermittent hypoxia (CIH) — a model of sleep-apnoea-related hypertension — daily H₂ gas inhalation significantly attenuated the rise in blood pressure. H₂ reduced sympathetic nervous system overactivity and improved vascular relaxation responses, with the antioxidant effect of H₂ (reducing 8-OHdG and increasing superoxide dismutase activity) identified as the likely mechanism. (Journal of Cellular Biochemistry, 2019.)", "assessment": "An informative preclinical rat study — not clinical evidence for human hypertension or sleep apnoea management. The finding that H₂ did not lower blood pressure in healthy rats (only in CIH-hypertensive ones) is an important specificity signal that reduces concern about overcorrection. The antioxidant mechanism (8-OHdG reduction, SOD increase) is consistent with H₂'s known properties. However, this is a rodent model of a specific hypertension subtype; no human patients were studied, and the H₂ inhalation protocol differs substantially from any practicable clinical delivery.", "abstract": "Molecular hydrogen is reported to be used medically to ameliorate various systemic pathological conditions. This study aimed to investigate the effect of hydrogen (H2 ) gas on hypertension induced by intermittent hypoxia in rats. The adult rats were exposed to chronic intermittent hypoxia (CIH) 8 hours/day for 5 weeks and/or H 2 gas 2 hours/day. We found that the systolic and diastolic blood pressure (BP) increased significantly in rats exposed to intermittent hypoxia, both of which were markedly attenuated after H treatment. Furthermore, intermittent hypoxia exposure elevated renal sympathetic nerve activity, consistent with plasma norepinephrine. Additionally, H 2 gas significantly improved CIH-induced abnormal vascular relaxation. Nevertheless, inhalation of H 2 gas alone did not cause such changes. Moreover, H 2 gas-treated rats exposed to CIH showed a significant reduction in 8-hydroxy-2 deoxyguanosine content and increases in superoxide dismutase activity, indicating improved oxidative stress. Taken together, these results indicate that H 2 gas has significant effects on the reduction of BP without any side effects. Mechanistically, inhibition of sympathetic activity and reduction of systemic vascular resistance may participate in this process via the antioxidant activity of H 2 .", "conclusion": "Taken together, these results indicate that H 2 gas has significant effects on the reduction of BP without any side effects. Mechanistically, inhibition of sympathetic activity and reduction of systemic vascular resistance may participate in this process via the antioxidant activity of H 2 ." }, { "pmid": "30367274", "year": 2018, "title": "Recent Advances in the Electro-Oxidation of Urea for Direct Urea Fuel Cell and Urea Electrolysis.", "title_en": null, "title_de": "Jüngste Fortschritte bei der Elektrooxidation von Harnstoff für die Direkt-Harnstoff-Brennstoffzelle und die Harnstoff-Elektrolyse.", "journal": "Topics in current chemistry (Cham)", "authors": "Ye et al.", "author_search": "ye ye", "doi": "10.1007/s41061-018-0219-y", "doi_url": "https://doi.org/10.1007/s41061-018-0219-y", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/30367274/", "url": "https://h2medicine.org/studies/study-ye-2018-recent-advances-electro-oxidation/", "methods": [ "unspecified" ], "indications": [ "sports-exercise" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2018 · Ye — Recent Advances in the Electro-Oxidation of Urea for Direct Urea Fuel Cell and Urea Electrolysis.", "summary": "This review covers recent advances in the electro-oxidation of urea — the electrochemical reaction that makes it possible to use urea (from urine, wastewater, or industrial sources) as a fuel in direct urea fuel cells, or as a feedstock to produce hydrogen gas through urea electrolysis. Development of improved catalysts is identified as the key bottleneck for both applications. (Topics in Current Chemistry, 2018.)", "assessment": "This is a chemistry/materials-science review — it has no direct relevance to therapeutic hydrogen medicine. It reviews electrochemical methods for urea oxidation as an approach to hydrogen production and fuel cells. No biological or health data are discussed. The connection to H₂ medicine is indirect: more efficient H₂ production technologies could eventually support the manufacturing of H₂-enriched solutions or gases — but this paper makes no claims about health effects and should not be cited as health evidence.", "abstract": "This paper provides an overview of recent advances in urea electro-oxidation. Urea sources are abundant from human urine, urea-containing wastewater, and industrial urea, thus becoming an attractive option as anodic fuel for the application in direct urea fuel cells (DUFCs). Besides, as a hydrogen-rich chemical fuel, urea can also be electrolyzed to produce hydrogen for energy storage in the near future. The exact mechanisms of urea decomposition are pretty different in alkaline or neutral mediums and are separately discussed in detail. More importantly, the development of anodic electro-catalysts is of great significance for improving the electrochemical performance of both DUFCs and urea electrolysis cells, which is systematically summarized in our review. Challenges and prospects on the future development of urea electro-oxidation are particularly proposed.", "conclusion": "More importantly, the development of anodic electro-catalysts is of great significance for improving the electrochemical performance of both DUFCs and urea electrolysis cells, which is systematically summarized in our review. Challenges and prospects on the future development of urea electro-oxidation are particularly proposed." }, { "pmid": "30107657", "year": 2018, "title": "[Research progress of hydrogen-rich saline for eye diseases].", "title_en": null, "title_de": "Forschungsfortschritt zu wasserstoffreicher Kochsalzlösung bei Augenerkrankungen.", "journal": "[Zhonghua yan ke za zhi] Chinese journal of ophthalmology", "authors": "Chen et al.", "author_search": "chen chen", "doi": "10.3760/cma.j.issn.0412-4081.2018.08.015", "doi_url": "https://doi.org/10.3760/cma.j.issn.0412-4081.2018.08.015", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/30107657/", "url": "https://h2medicine.org/studies/study-chen-2018-research-progress-saline-eye/", "methods": [ "saline-iv", "drinking-hrw" ], "indications": [ "cardiovascular", "respiratory", "kidney-dialysis", "eye", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2018 · Chen — Research progress of hydrogen-rich saline for eye diseases.", "summary": "This Chinese-language review summarizes the published research on hydrogen-rich saline (and hydrogen-rich water) for the treatment of eye diseases, including glaucoma, retinal ischemia, and other ocular conditions. The authors note that while H₂ has shown positive results in nervous, digestive, respiratory, cardiac, and renal disease research, ophthalmology-specific studies remain sparse. (Chinese Journal of Ophthalmology, 2018.)", "assessment": "This is a narrative review — it synthesizes preclinical and limited clinical evidence for H₂ in ocular disease, but does not provide new experimental data. The review explicitly acknowledges that ophthalmological H₂ research is sparse compared to other disease areas. No systematic search strategy or inclusion criteria are described in the available abstract. The level of evidence is low (narrative review of heterogeneous preclinical and early clinical literature), and the paper should be read as a field-orientation summary rather than strong clinical evidence. No treatment conclusions can be drawn for human eye diseases.", "abstract": "As an antioxidant, hydrogen-rich water has been widely studied in recent years. It is mild enough neither to disturb metabolic redox reactions nor to affect signaling reactive oxygen species. Therefore, there should be no or few adverse effects of H(2). Numerous studies in biology and medicine show that hydrogen-rich water has achieved good results in nervous system, digestive system, respiratory system, heart and kidney diseases. At present, there are few studies on the treatment of eye diseases with hydrogen-rich water. This review summarizes the research progress of hydrogen-rich water for eye diseases in the domestic and foreign literatures. (Chin J Ophthalmol, 2018, 54: 631-635).", "conclusion": "This review summarizes the research progress of hydrogen-rich water for eye diseases in the domestic and foreign literatures. (Chin J Ophthalmol, 2018, 54: 631-635)." }, { "pmid": "29763888", "year": 2018, "title": "Hydrogen Therapy in Cardiovascular and Metabolic Diseases: from Bench to Bedside.", "title_en": null, "title_de": "Wasserstofftherapie bei kardiovaskulären und metabolischen Erkrankungen: vom Labor zum Krankenbett", "journal": "Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology", "authors": "Zhang et al.", "author_search": "zhang zhang", "doi": "10.1159/000489737", "doi_url": "https://doi.org/10.1159/000489737", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/29763888/", "url": "https://h2medicine.org/studies/study-zhang-2018-cardiovascular-metabolic-diseases-bench/", "methods": [ "unspecified" ], "indications": [ "diabetes", "metabolic", "liver", "sports-exercise", "cardiovascular" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2018 · Zhang — Hydrogen Therapy in Cardiovascular and Metabolic Diseases: from Bench to Bedside", "summary": "This review summarises a decade of H₂ research in cardiovascular and metabolic diseases — from animal models to early clinical trials. Areas covered include atherosclerosis, cardiac ischaemia, hypertrophic remodelling, heart transplantation injury, obesity, and diabetes. The authors conclude that H₂-based therapies show broad potential in cardiometabolic disease, though most mechanistic work remains preclinical. (Cellular Physiology and Biochemistry, 2018.)", "assessment": "This is a narrative review, not a meta-analysis or clinical trial. Its value lies in breadth: it assembles diverse preclinical and a few clinical signals into one readable map. Limitations: no quantitative pooling of effects, publication bias likely, many cited studies are small animal experiments whose translational relevance to humans is unproven. The review does not perform a systematic literature search, so coverage may be selective. It is a good entry point but should not be read as definitive proof of clinical efficacy in any of the listed conditions.", "abstract": "Hydrogen (H2) is colorless, odorless, and the lightest of gas molecules. Studies in the past ten years have indicated that H2 is extremely important in regulating the homeostasis of the cardiovascular system and metabolic activity. Delivery of H2 by various strategies improves cardiometabolic diseases, including atherosclerosis, vascular injury, ischemic or hypertrophic ventricular remodeling, intermittent hypoxia- or heart transplantation-induced heart injury, obesity and diabetes in animal models or in clinical trials. The purpose of this review is to summarize the physical and chemical properties of H2, and then, the functions of H2 with an emphasis on the therapeutic potential and molecular mechanisms involved in the diseases above. We hope this review will provide the future outlook of H2-based therapies for cardiometabolic disease.", "conclusion": "The purpose of this review is to summarize the physical and chemical properties of H2, and then, the functions of H2 with an emphasis on the therapeutic potential and molecular mechanisms involved in the diseases above. We hope this review will provide the future outlook of H2-based therapies for cardiometabolic disease." }, { "pmid": "29759891", "year": 2018, "title": "The putative role of oxidative stress and inflammation in the pathophysiology of sleep dysfunction across neuropsychiatric disorders: Focus on chronic fatigue syndrome, bipolar disorder and multiple sclerosis.", "title_en": null, "title_de": "Die mutmaßliche Rolle von oxidativem Stress und Entzündung in der Pathophysiologie von Schlafstörungen bei neuropsychiatrischen Erkrankungen", "journal": "Sleep medicine reviews", "authors": "Morris et al.", "author_search": "morris morris", "doi": "10.1016/j.smrv.2018.03.007", "doi_url": "https://doi.org/10.1016/j.smrv.2018.03.007", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/29759891/", "url": "https://h2medicine.org/studies/study-morris-2018-putative-oxidative-stress-inflammation/", "methods": [ "unspecified" ], "indications": [ "sports-exercise", "neurology", "cancer", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2018 · Morris — The putative role of oxidative stress and inflammation in the pathophysiology of sleep dysfunction across neuropsychiatric disorders", "summary": "This review proposes that oxidative stress, neuroinflammation, and mitochondrial dysfunction are shared drivers of sleep disturbances in chronic fatigue syndrome, bipolar disorder, and multiple sclerosis. Molecular hydrogen is mentioned among novel therapeutic candidates targeting these pathways alongside melatonin. This is a theoretical framework paper, not a clinical H₂ study. (Sleep Medicine Reviews, 2018.)", "assessment": "This paper does not test H₂ in any experiment — it is a theoretical review that mentions molecular hydrogen as a plausible candidate within a broader redox-inflammation framework. Its relevance to H₂ research is indirect: it provides mechanistic context for why antioxidant strategies might help sleep in neuro-immune disease, but offers no clinical data. Readers should not interpret this as evidence that H₂ improves sleep in any of the three disorders. The review itself has the usual limitations of narrative overviews: no systematic search strategy, no effect sizes, risk of confirmation bias in the causal model proposed.", "abstract": "Sleep and circadian abnormalities are prevalent and burdensome manifestations of diverse neuro-immune diseases, and may aggravate the course of several neuropsychiatric disorders. The underlying pathophysiology of sleep abnormalities across neuropsychiatric disorders remains unclear, and may involve the inter-play of several clinical variables and mechanistic pathways. In this review, we propose a heuristic framework in which reciprocal interactions of immune, oxidative and nitrosative stress, and mitochondrial pathways may drive sleep abnormalities across potentially neuroprogressive disorders. Specifically, it is proposed that systemic inflammation may activate microglial cells and astrocytes in brain regions involved in sleep and circadian regulation. Activated glial cells may secrete pro-inflammatory cytokines (for example, interleukin-1 beta and tumour necrosis factor alpha), nitric oxide and gliotransmitters, which may influence the expression of key circadian regulators (e.g., the Circadian Locomotor Output Cycles Kaput (CLOCK) gene). Furthermore, sleep disruption may further aggravate oxidative and nitrosative, peripheral immune activation, and (neuro) inflammation across these disorders in a vicious pathophysiological loop. This review will focus on chronic fatigue syndrome, bipolar disorder, and multiple sclerosis as exemplars of neuro-immune disorders. We conclude that novel therapeutic targets exploring immune and oxidative & nitrosative pathways (p.e. melatonin and molecular hydrogen) hold promise in alleviating sleep and circadian dysfunction in these disorders.", "conclusion": "We conclude that novel therapeutic targets exploring immune and oxidative & nitrosative pathways (p.e. melatonin and molecular hydrogen) hold promise in alleviating sleep and circadian dysfunction in these disorders." }, { "pmid": "29683480", "year": 2018, "title": "Metabolism of hydrogen gases and bile acids in the gut microbiome.", "title_en": null, "title_de": "Metabolismus von Wasserstoffgasen und Gallensäuren im Darmmikrobiom", "journal": "FEBS letters", "authors": "Hylemon et al.", "author_search": "hylemon hylemon", "doi": "10.1002/1873-3468.13064", "doi_url": "https://doi.org/10.1002/1873-3468.13064", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/29683480/", "url": "https://h2medicine.org/studies/study-hylemon-2018-metabolism-gases-bile-acids/", "methods": [ "inhalation" ], "indications": [ "metabolic", "liver", "sports-exercise" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2018 · Hylemon — Metabolism of hydrogen gases and bile acids in the gut microbiome", "summary": "This review examines how gut bacteria produce and consume molecular hydrogen (H₂) during fermentation, and how these processes interact with bile acid metabolism. H₂ generation is a normal part of anaerobic gut ecology — it influences microbial community structure and host physiology. The paper does not investigate therapeutic H₂ administration in humans or animals. (FEBS Letters, 2018.)", "assessment": "This is a basic-science review about microbial physiology, not a therapeutic H₂ study. It clarifies an important distinction: the H₂ discussed here is endogenous — produced by gut bacteria — rather than H₂ administered therapeutically. The findings are scientifically interesting for understanding how gut H₂ partial pressure shapes microbial communities and indirectly modulates bile acid metabolism, but they do not provide evidence that drinking hydrogen-rich water or inhaling H₂ produces the same effects. Translational relevance to clinical H₂ supplementation is speculative at this stage.", "abstract": "The human gut microbiome refers to a highly diverse microbial ecosystem, which has a symbiotic relationship with the host. Molecular hydrogen (H2 ) and carbon dioxide (CO2 ) are generated by fermentative metabolism in anaerobic ecosystems. H2 generation and oxidation coupled to CO2 reduction to methane or acetate help maintain the structure of the gut microbiome. Bile acids are synthesized by hepatocytes from cholesterol in the liver and are important regulators of host metabolism. In this Review, we discuss how gut bacteria metabolize hydrogen gases and bile acids in the intestinal tract and the consequences on host physiology. Finally, we focus on bile acid metabolism by the Actinobacterium Eggerthella lenta. Eggerthella lenta appears to couple hydroxyl group oxidations to reductive acetogenesis under a CO2 or N2 atmosphere, but not under H2 . Hence, at low H2 levels, E. lenta is proposed to use NADH from bile acid hydroxyl group oxidations to reduce CO2 to acetate.", "conclusion": "Hence, at low H2 levels, E. lenta is proposed to use NADH from bile acid hydroxyl group oxidations to reduce CO2 to acetate." }, { "pmid": "30207619", "year": 2018, "title": "Randomized, double-blind, multicenter trial of hydrogen water for Parkinson's disease.", "title_en": null, "title_de": "Randomisierte, doppelblinde, multizentrische Studie zu Wasserstoffwasser bei Morbus Parkinson", "journal": "Movement disorders : official journal of the Movement Disorder Society", "authors": "Yoritaka et al.", "author_search": "yoritaka yoritaka", "doi": "10.1002/mds.27472", "doi_url": "https://doi.org/10.1002/mds.27472", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/30207619/", "url": "https://h2medicine.org/studies/study-yoritaka-2018-multicenter-parkinson-disease/", "methods": [ "drinking-hrw" ], "indications": [ "neurology" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2018 · Yoritaka — Randomized, Double-Blind, Multicenter Trial of Hydrogen Water for Parkinson's Disease", "summary": "This multicenter, randomized, double-blind trial tested hydrogen-rich water in Parkinson's patients — and did not find a statistically significant overall improvement against placebo. The study is nonetheless scientifically important as it represents one of the most rigorous H₂ trial designs in neurology to date. (Movement Disorders, 2018.)", "assessment": "This trial deserves recognition for its methodological quality — multicenter, randomized, double-blind, placebo-controlled — which is rare in H₂ clinical research. Honest limitations: the full abstract was not available in the source data for this record, preventing direct quotation or detailed endpoint reporting. Based on published literature, the primary endpoint did not show statistically significant improvement across the full cohort. Subgroup signals (e.g., in patients not on specific medications) were reported but must be interpreted cautiously as hypothesis-generating only. This trial is essential context for any claims about H₂ and Parkinson's disease.", "abstract": null, "conclusion": null }, { "pmid": "29798076", "year": 2018, "title": "[Clinical study of hydrogen-rich saline in the treatment of moderate to severe allergic rhinitis].", "title_en": null, "title_de": "Klinische Studie zu wasserstoffreicher Kochsalzlösung in der Behandlung von mittelschwerer bis schwerer allergischer Rhinitis", "journal": "Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery", "authors": "Jin et al.", "author_search": "jin jin", "doi": "10.13201/j.issn.1001-1781.2018.07.004", "doi_url": "https://doi.org/10.13201/j.issn.1001-1781.2018.07.004", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/29798076/", "url": "https://h2medicine.org/studies/study-jin-2018-saline-moderate-severe-allergic/", "methods": [ "saline-iv", "bath-topical" ], "indications": [ "allergy", "fundamentals-safety" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2018 · Jin — Clinical Study of Hydrogen-Rich Saline in the Treatment of Moderate to Severe Allergic Rhinitis", "summary": "Nasal lavage with hydrogen-rich saline significantly improved symptoms, signs, and quality of life in patients with moderate-to-severe allergic rhinitis — with no relevant adverse effects. This randomized double-blind self-control study with 20 patients is one of the few H₂ trials targeting the upper respiratory tract. (Journal of Clinical Otorhinolaryngology Head and Neck Surgery, 2018.)", "assessment": "A biologically plausible and clinically interesting study using H₂ in a novel topical delivery route. The self-control crossover design is efficient but limits generalizability compared to parallel-group RCTs. Limitations: n = 20 is small; the journal is a Chinese specialty publication and the article appears in Chinese (translated title), which limits independent verification of statistical details; the H₂ concentration of the lavage solution is not specified in the available data; follow-up duration is not clear. The results are encouraging but should be replicated in larger, properly powered trials before clinical recommendations can be made.", "abstract": "Objective:To investigate the effectiveness and safety of nasal lavage with hydrogen-rich saline in the treatment of moderate to severe allergic rhinitis.Method:Twenty patients with moderate to severe persistent allergic rhinitis were treated with normal saline and hydrogen-rich saline lavage the nasal cavity. The study was randomized doubl-blind self-control study. The symptoms and signs score, treatment index and total effective rate were evaluated before and after treatment, and the nasal conjunctivitis related quality of life questionnaire (BQLQ) was used to evaluate the life quality of patients.Result:There were significant differences of the symptoms, signs scores, the treatment index, the total efficiency and BQLQ between the two kinds of lavage fluid used for patients before and after treatment(P<0.05). No significant adverse reactions occurred during follow-up.Conclusion:Hydrogen-enriched saline is safe and effective for allergic rhinitis.", "conclusion": "Hydrogen-enriched saline is safe and effective for allergic rhinitis." }, { "pmid": "29110615", "year": 2018, "title": "Effects of Molecular Hydrogen Assessed by an Animal Model and a Randomized Clinical Study on Mild Cognitive Impairment.", "title_en": null, "title_de": "Wirkungen von molekularem Wasserstoff bei leichter kognitiver Beeinträchtigung, untersucht anhand eines Tiermodells und einer randomisierten klinischen Studie", "journal": "Current Alzheimer research", "authors": "Nishimaki et al.", "author_search": "nishimaki nishimaki", "doi": "10.2174/1567205014666171106145017", "doi_url": "https://doi.org/10.2174/1567205014666171106145017", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/29110615/", "url": "https://h2medicine.org/studies/study-nishimaki-2018-assessed-animal-model-mild/", "methods": [ "drinking-hrw" ], "indications": [ "neurology", "cardiovascular", "oxidative-stress" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2018 · Nishimaki — Effects of Molecular Hydrogen Assessed by an Animal Model and a Randomized Clinical Study on Mild Cognitive Impairment", "summary": "In a randomized double-blind placebo-controlled trial with 73 patients with mild cognitive impairment (MCI), H₂-water did not improve overall cognitive scores — but a specific genetic subgroup (APOE4 carriers) showed significant improvement. Parallel animal data in an oxidative stress dementia model supported the biological plausibility. (Current Alzheimer Research, 2018.)", "assessment": "A methodologically solid RCT with an honest null result in the primary analysis. The APOE4 subgroup finding is intriguing and biologically plausible but must not be overinterpreted — it was not a pre-specified primary outcome and represents a subgroup of a 73-person trial. Limitations: dose of H₂-water is low (~300 mL/day at unspecified concentration — far below doses used in some other trials); one year is a meaningful follow-up but Alzheimer's progression is slow and longer studies would be more informative; APOE4 subgroup analysis is exploratory. This study contributes important nuance: H₂ may not be uniformly beneficial across all cognitive impairment patients — genetic predisposition to oxidative stress may be a key moderator.", "abstract": "BACKGROUND: Oxidative stress is one of the causative factors in the pathogenesis of neurodegenerative diseases including mild cognitive impairment (MCI) and dementia. We previously reported that molecular hydrogen (H2) acts as a therapeutic and preventive antioxidant. OBJECTIVE: We assess the effects of drinking H2-water (water infused with H2) on oxidative stress model mice and subjects with MCI. METHODS: Transgenic mice expressing a dominant-negative form of aldehyde dehydrogenase 2 were used as a dementia model. The mice with enhanced oxidative stress were allowed to drink H2-water. For a randomized double-blind placebo-controlled clinical study, 73 subjects with MCI drank ~300 mL of H2-water (H2-group) or placebo water (control group) per day, and the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) scores were determined after 1 year. RESULTS: In mice, drinking H2-water decreased oxidative stress markers and suppressed the decline of memory impairment and neurodegeneration. Moreover, the mean lifespan in the H2-water group was longer than that of the control group. In MCI subjects, although there was no significant difference between the H2- and control groups in ADAS-cog score after 1 year, carriers of the apolipoprotein E4 (APOE4) genotype in the H2-group were improved significantly on total ADAS-cog score and word recall task score (one of the sub-scores in the ADAS-cog score). CONCLUSION: H2-water may have a potential for suppressing dementia in an oxidative stress model and in the APOE4 carriers with MCI.", "conclusion": "H2-water may have a potential for suppressing dementia in an oxidative stress model and in the APOE4 carriers with MCI." }, { "pmid": "28560519", "year": 2018, "title": "Molecular hydrogen affects body composition, metabolic profiles, and mitochondrial function in middle-aged overweight women.", "title_en": null, "title_de": "Molekularer Wasserstoff beeinflusst Körperzusammensetzung, Stoffwechselprofile und mitochondriale Funktion bei übergewichtigen Frauen mittleren Alters", "journal": "Irish journal of medical science", "authors": "Korovljev et al.", "author_search": "korovljev korovljev", "doi": "10.1007/s11845-017-1638-4", "doi_url": "https://doi.org/10.1007/s11845-017-1638-4", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/28560519/", "url": "https://h2medicine.org/studies/study-korovljev-2018-affects-body-composition-metabolic/", "methods": [ "drinking-hrw" ], "indications": [ "diabetes", "metabolic", "fundamentals-safety" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2018 · Korovljev — Molecular Hydrogen Affects Body Composition, Metabolic Profiles, and Mitochondrial Function in Middle-Aged Overweight Women", "summary": "A double-blind, placebo-controlled crossover pilot trial in 10 overweight women found that hydrogen-generating mineral caplets significantly reduced body fat percentage and triglycerides while improving fasting insulin levels — without affecting body weight or BMI. This is one of the first controlled human studies on H₂ and metabolic parameters. (Irish Journal of Medical Science, 2018.)", "assessment": "An innovative pilot with mechanistically plausible results, but n = 10 is very small and the study is explicitly a pilot. Limitations: tiny sample (10 women only — results may not generalize to men or other age groups); 4-week intervention is short; the H₂ dose (~6 ppm/day via mineral caplets) is lower than many inhalation or HRW drinking studies; „mitochondrial function“ in the title is not clearly quantified in the available abstract; multiple comparisons increase false-positive risk; the trial is registered (NCT02832219) which adds credibility. The insulin result in particular warrants follow-up in a larger trial — if replicated, it would be clinically significant for metabolic syndrome management.", "abstract": "BACKGROUND: Molecular hydrogen (H2) effectively treats obesity-related disorders in animal models, yet no studies have investigated the effectiveness and safety of H2 for improving biomarkers of obesity in humans. AIM: In this double blind, placebo-controlled, crossover pilot trial, we evaluated the effects of H2 intervention on body composition, hormonal status, and mitochondrial function in ten (n = 10) middle-aged overweight women. METHODS: Volunteers received either hydrogen-generating minerals (supplying ~6 ppm of H2 per day) or placebo by oral administration of caplets for 4 weeks. The primary end-point of treatment efficacy was the change in the body fat percentage from baseline to 4 weeks. In addition, assessment of other body composition indices, screening laboratory studies, and evaluation of side effects were performed before and at follow-up. Clinical trial registration www.clinicaltrials.gov , ID number NCT02832219. RESULTS: No significant differences were observed between treatment groups for changes in weight, body mass index, and body circumferences at 4-week follow-up (P > 0.05). H2 treatment significantly reduced body fat percentage (3.2 vs. 0.9%, P = 0.05) and arm fat index (9.7 vs. 6.0%, P = 0.01) compared to placebo administration, respectively. This was accompanied by a significant drop in serum triglycerides after H2 intervention comparing to placebo (21.3 vs. 6.5%; P = 0.04), while other blood lipids remained stable during the study (P > 0.05). Fasting serum insulin levels dropped by 5.4% after H2 administration, while placebo intervention augmented insulin response by 29.3% (P = 0.01). CONCLUSIONS: It appears that orally administered H2 as a blend of hydrogen-generating minerals might be a beneficial agent in the management of body composition and insulin resistance in obesity.", "conclusion": "It appears that orally administered H2 as a blend of hydrogen-generating minerals might be a beneficial agent in the management of body composition and insulin resistance in obesity." }, { "pmid": "30586410", "year": 2018, "title": "Quantification of hydrogen production by intestinal bacteria that are specifically dysregulated in Parkinson's disease.", "title_en": null, "title_de": "Quantifizierung der Wasserstoffproduktion durch Darmbakterien, die bei Morbus Parkinson spezifisch dysreguliert sind", "journal": "PloS one", "authors": "Suzuki et al.", "author_search": "suzuki suzuki", "doi": "10.1371/journal.pone.0208313", "doi_url": "https://doi.org/10.1371/journal.pone.0208313", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/30586410/", "url": "https://h2medicine.org/studies/study-suzuki-2018-quantification-production-intestinal-bacteria/", "methods": [], "indications": [ "neurology" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "byproduct", "headline": "2018 · Suzuki — Quantification of Hydrogen Production by Intestinal Bacteria That Are Specifically Dysregulated in Parkinson's Disease", "summary": "Parkinson's disease patients have significantly reduced intestinal hydrogen production — approximately 2.2-fold less than healthy controls — due to a specific dysbiosis of hydrogen-producing gut bacteria. This mechanistic study bridges gut microbiome research with H₂ neurology, suggesting that endogenous H₂ deficiency may contribute to PD progression. (PLOS ONE, 2018.)", "assessment": "A well-executed mechanistic study with an important hypothesis for the H₂-Parkinson's field. The computational simulation approach — using measured bacterial H₂ production rates applied to known PD microbiome data — is methodologically clever. Limitations: this is a simulation/calculation study, not a direct measurement of H₂ production in PD patients in vivo; causality cannot be established — reduced H₂-producing bacteria could be a consequence of PD pathology rather than a cause; the connection between gut H₂ levels and brain neuroprotection requires further mechanistic support; the study confirms an association, not a therapeutic effect. This work provides important biological rationale for why some PD patients might respond better to exogenous H₂ supplementation than others.", "abstract": "Oral administration of hydrogen water ameliorates Parkinson's disease (PD) in rats, mice, and humans. We previously reported that the number of putative hydrogen-producing bacteria in intestinal microbiota is low in PD compared to controls. We also reported that the amount of hydrogen produced by ingestion of lactulose is low in PD patients. The decreased hydrogen production by intestinal microbiota may be associated with the development and progression of PD. We measured the amount of hydrogen production using gas chromatography by seven bacterial strains, which represented seven major intestinal bacterial groups/genera/species. Blautia coccoides and Clostridium leptum produced the largest amount of hydrogen. Escherichia coli and Bacteroides fragilis constituted the second group that produced hydrogen 34- to 93-fold lower than B. coccoides. Bifidobacterium pseudocatenulatum and Atopobium parvulum constituted the third group that produced hydrogen 559- to 2164-fold lower than B. coccoides. Lactobacillus casei produced no detectable hydrogen. Assuming that taxonomically neighboring strains have similar hydrogen production, we simulated hydrogen production using intestinal microbiota that we previously reported, and found that PD patients produce a 2.2-fold lower amount of intestinal hydrogen compared to controls. The lower amount of intestinal hydrogen production in PD was also simulated in cohorts of two other countries. The number of hydrogen-producing intestinal bacteria may be associated with the development and progression of PD. Further studies are required to prove its beneficial effect.", "conclusion": "The number of hydrogen-producing intestinal bacteria may be associated with the development and progression of PD. Further studies are required to prove its beneficial effect." }, { "pmid": "30568387", "year": 2018, "title": "Effects of alkaline-electrolyzed and hydrogen-rich water, in a high-fat-diet nonalcoholic fatty liver disease mouse model.", "title_en": null, "title_de": "Wirkungen von alkalisch-elektrolysiertem und wasserstoffreichem Wasser in einem Mausmodell der nichtalkoholischen Fettlebererkrankung mit fettreicher Ernährung", "journal": "World journal of gastroenterology", "authors": "Jackson et al.", "author_search": "jackson jackson", "doi": "10.3748/wjg.v24.i45.5095", "doi_url": "https://doi.org/10.3748/wjg.v24.i45.5095", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/30568387/", "url": "https://h2medicine.org/studies/study-jackson-2018-alkaline-electrolyzed-high-fat/", "methods": [ "drinking-hrw" ], "indications": [ "metabolic", "liver" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2018 · Jackson — Effects of alkaline-electrolyzed and hydrogen-rich water, in a high-fat-diet nonalcoholic fatty liver disease mouse model", "summary": "In mice fed a high-fat diet, only high-concentration hydrogen-rich water (0.8 mg H₂/L) — not electrolyzed-alkaline water with low H₂ (0.2 mg/L) — significantly reduced fat mass gain and liver lipid accumulation. The study concludes that H₂ is the therapeutic agent in electrolyzed water, and that dose matters: low H₂ concentrations were ineffective. This is a mouse study; results cannot be directly extrapolated to humans. (World Journal of Gastroenterology, 2018.)", "assessment": "A carefully controlled animal study with an honest null result for low-H₂ alkaline water — which adds credibility. The dose-response finding (0.3 mg/L ineffective, 0.8 mg/L effective) is practically relevant for product evaluation. Critical limitations: this is a mouse model; the high-fat-diet NAFLD mouse does not perfectly replicate human NAFLD progression. No human data exist from this group. Results should be interpreted as hypothesis-generating for dose thresholds, not as proof of human efficacy. Translation to humans requires controlled clinical trials.", "abstract": "AIM: To identify the effect of hydrogen-rich water (HRW) and electrolyzed-alkaline water (EAW) on high-fat-induced non-alcoholic fatty acid disease in mice. METHODS: Mice were divided into four groups: (1) Regular diet (RD)/regular water (RW); (2) high-fat diet (HFD)/RW; (3) RD/EAW; and (4) HFD/EAW. Weight and body composition were measured. After twelve weeks, animals were sacrificed, and livers were processed for histology and reverse-transcriptase polymerase chain reaction. A similar experiment was performed using HRW to determine the influence and importance of molecular hydrogen (H2) in EAW. Finally, we compared the response of hepatocytes isolated from mice drinking HRW or RW to palmitate overload. RESULTS: EAW had several properties important to the study: (1) pH = 11; (2) oxidation-reduction potential of -495 mV; and (3) H2 = 0.2 mg/L. However, in contrast to other studies, there were no differences between the groups drinking EAW or RW in either the RD or HFD groups. We hypothesized that the null result was due to low H2 concentrations. Therefore, we evaluated the effects of RW and low and high HRW concentrations (L-HRW = 0.3 mg H2/L and H-HRW = 0.8 mg H2/L, respectively) in mice fed an HFD. Compared to RW and L-HRW, H-HRW resulted in a lower increase in fat mass (46% vs 61%), an increase in lean body mass (42% vs 28%), and a decrease in hepatic lipid accumulation (P < 0.01). Lastly, exposure of hepatocytes isolated from mice drinking H-HRW to palmitate overload demonstrated a protective effect from H2 by reducing hepatocyte lipid accumulation in comparison to mice drinking regular water. CONCLUSION: H2 is the therapeutic agent in electrolyzed-alkaline water and attenuates HFD-induced nonalcoholic fatty liver disease in mice.", "conclusion": "H2 is the therapeutic agent in electrolyzed-alkaline water and attenuates HFD-induced nonalcoholic fatty liver disease in mice." }, { "pmid": "30419521", "year": 2018, "title": "Efficient discrimination of natural stereoisomers of chicoric acid, an HIV-1 integrase inhibitor.", "title_en": null, "title_de": "Effiziente Unterscheidung natürlicher Stereoisomere von Cichoriensäure, einem HIV-1-Integrase-Inhibitor", "journal": "Journal of photochemistry and photobiology. B, Biology", "authors": "Nobela et al.", "author_search": "nobela nobela", "doi": "10.1016/j.jphotobiol.2018.10.025", "doi_url": "https://doi.org/10.1016/j.jphotobiol.2018.10.025", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/30419521/", "url": "https://h2medicine.org/studies/study-nobela-2018-efficient-discrimination-natural-stereoisomers/", "methods": [ "unspecified" ], "indications": [ "cancer" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2018 · Nobela — Efficient discrimination of natural stereoisomers of chicoric acid, an HIV-1 integrase inhibitor", "summary": "This in-vitro chemistry study identifies and distinguishes two stereoisomers of chicoric acid — a plant-derived HIV-1 integrase inhibitor — using LC-MS, UV isomerisation, molecular dynamics, and quantum-chemical calculations. The mention of hydrogen in this paper refers exclusively to intramolecular hydrogen bonding within the chicoric acid molecule, not to molecular hydrogen (H₂) as a therapeutic gas. This study has no direct relevance to H₂ therapy research. (Journal of Photochemistry and Photobiology B: Biology, 2018.)", "assessment": "This paper is not a molecular hydrogen (H₂) therapy study. The hydrogen referenced is hydrogen bonding in an organic molecule — a standard chemical concept. The study is well-executed analytical chemistry and computational biology, but its inclusion in an H₂-medicine context reflects a keyword mismatch, not scientific relevance to therapeutic H₂. Readers seeking evidence for H₂ inhalation, hydrogen-rich water, or related applications will find nothing applicable here. Methodological note: this is an in-vitro/computational study; even if it were about H₂, animal and human validation would still be required.", "abstract": "Plants from the Asteraceae family are known to contain a wide spectrum of phytochemicals with various nutraceutical properties. One important phytochemical, chicoric acid (CA), is reported to exist in plants, such as Sonchus oleraceus and Bidens pilosa, as stereoisomers. These CA molecules occur either as the naturally abundant RR-chicoric acid (RR-CA), or the less abundant RS-chicoric acid (RS-CA), also known as meso-chicoric acid. To date, little is known about the biological activity of RS-CA, but there is evidence of its anti-human immunodeficiency virus (HIV) properties. In this study, a reliable analytical method was developed to distinguish between the two stereoisomers detected in S. oleraceus and B. pilosa. For structure identification and characterization of CA molecules, liquid chromatography-mass spectrometry (LC-MS) was used in combination with ultraviolet radiation (UV)-induced geometrical isomerization, molecular dynamics (MD) simulations, and density functional theory (DFT) models. Optimized structures from DFT calculations were used for docking studies against the HIV-1 integrase enzyme. Different retention times on the reverse phase chromatograms revealed that the plants produce two different CA stereoisomers: S. oleraceus produced the RR-CA isomer, while B. pilosa produced the RS-CA isomer. DFT results demonstrated the RR-CA molecule was more stable than RS-CA due to the stabilizing force of intra-molecular hydrogen bonding. Differences in the HIV-1 integrase enzyme binding modes were observed, with the RR-CA being a more potent inhibitor than the RS-CA molecule. The results highlight the significance of plant metabolite structural complexity from both chemical and biological perspectives. Furthermore, the study demonstrates that induced-formation of geometrical isomers, in combination with the predictive ability of DFT models and the resolving power of the LC-MS, can be exploited to distinguish structurally closely related compounds, such as stereoisomers.", "conclusion": "The results highlight the significance of plant metabolite structural complexity from both chemical and biological perspectives. Furthermore, the study demonstrates that induced-formation of geometrical isomers, in combination with the predictive ability of DFT models and the resolving power of the LC-MS, can be exploited to distinguish structurally closely related compounds, such as stereoisomers" }, { "pmid": "30396494", "year": 2018, "title": "Molecular hydrogen may enhance the production of testosterone hormone in male infertility through hormone signal modulation and redox balance.", "title_en": null, "title_de": "Molekularer Wasserstoff könnte die Testosteronproduktion bei männlicher Infertilität durch Modulation von Hormonsignalen und Redox-Gleichgewicht steigern", "journal": "Medical hypotheses", "authors": "Begum et al.", "author_search": "begum begum", "doi": "10.1016/j.mehy.2018.09.001", "doi_url": "https://doi.org/10.1016/j.mehy.2018.09.001", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/30396494/", "url": "https://h2medicine.org/studies/study-begum-2018-may-enhance-production-testosterone/", "methods": [ "unspecified" ], "indications": [ "metabolic", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2018 · Begum — Molecular hydrogen may enhance the production of testosterone hormone in male infertility through hormone signal modulation and redox balance", "summary": "This is a theoretical hypothesis paper proposing that molecular hydrogen (H₂) might improve testosterone production in male infertility by reducing oxidative stress and modulating intracellular signalling pathways. No experiments were performed; the claims are mechanistic speculation based on known H₂ biology and published literature on ROS and Leydig cell function. No human or animal data support the hypothesis at this stage. (Medical Hypotheses, 2018.)", "assessment": "This is a hypothesis paper only — it contains no experiments and no new data. It represents an interesting mechanistic idea that could guide future research in male infertility and H₂, but it provides zero clinical evidence that H₂ administration improves testosterone levels or fertility outcomes in humans. The theoretical framework is plausible given what is known about H₂ and ROS scavenging, but it remains unvalidated. Experimental confirmation — ideally in animal models first, then human trials — is required before any conclusions can be drawn. Null and negative results in future experiments are equally possible.", "abstract": "Since the discovery of molecular hydrogen (H2) as a selective scavenger of free radicals like reactive oxygen species (ROS) and reactive nitrogen species (RNS), numerous studies have proved the potential application of H2 in therapeutic and preventative medicine. Moreover, H2 can regulate the intracellular signal as a signal modulator. However, it is still unclear in cell signaling involved in testosterone hormone production. Male fertility depends on the intra-testicular testosterone concentration, which is produced by the Leydig cell in the seminiferous tubules in testes. Although moderate amounts of ROS are needed for normal sperm function, the higher amounts might decrease testosterone production. High ROS decreases testosterone hormone production by dysregulation of hormonal signal from the hypothalamus to the Leydig cell as a result of redox imbalance. Lower level of testosterone fails to support the Leydig cell for the progression of spermatogenesis. Superoxide anion (O2-), hydroxyl radical (OH) and peroxynitrite (ONOO-) could also attack the DNA, lipid and protein, disrupting sperm structure and function and aggravating the milieu of male fertility and spermatogenesis. H2 regulates intracellular MAPK downstream cAMP signal and Ca2+ signal as a signal modulator to antagonize ROS signaling. Thus H2 can play a role in modulating signals involved in testosterone hormone production to improve male fertility caused by redox imbalance. We therefore hypothesize that molecular hydrogen may enhance testosterone production via cellular redox balance. By this hypothesis, we anticipate that molecular hydrogen may be an effective remedy in male infertility.", "conclusion": "We therefore hypothesize that molecular hydrogen may enhance testosterone production via cellular redox balance. By this hypothesis, we anticipate that molecular hydrogen may be an effective remedy in male infertility." }, { "pmid": "30382050", "year": 2018, "title": "[Immunological Effect of Hydrogen Gas-Hydrogen Gas Improves Clinical Outcomes of Cancer Patients].", "title_en": null, "title_de": "Immunologische Wirkung von Wasserstoffgas: Wasserstoffgas verbessert die klinischen Ergebnisse von Krebspatienten", "journal": "Gan to kagaku ryoho. Cancer & chemotherapy", "authors": "Akagi", "author_search": "akagi akagi", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/30382050/", "url": "https://h2medicine.org/studies/study-akagi-2018-immunological-improves-outcomes-cancer/", "methods": [ "inhalation" ], "indications": [ "cancer" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2018 · Akagi — Immunological Effect of Hydrogen Gas: Hydrogen Gas Improves Clinical Outcomes of Cancer Patients", "summary": "In a cohort of 55 Stage IV colorectal cancer patients, hydrogen gas inhalation reduced the proportion of exhausted immune cells (terminal PD-1⁺ CD8⁺ T cells) in 63.6% of patients, and patients who combined H₂ inhalation with nivolumab immunotherapy showed significantly longer overall survival than nivolumab alone. This is a landmark — though non-randomized — observation in oncology. (Gan to Kagaku Ryoho, 2018.)", "assessment": "A highly provocative and mechanistically innovative study — if the combination effect with nivolumab replicates, it would be a major finding. Critical limitations: this is not a randomized controlled trial — allocation to H₂ + nivolumab vs. nivolumab alone was not randomized, introducing significant selection bias; n = 26 in the combination subset is very small; no blinding; the immunological data interpretation (63.6% vs. 70.9%) is confusing and likely reflects different patient/timepoint comparisons; the journal is a Japanese oncology specialty publication (some difficulty in independent external verification). This study must be treated as hypothesis-generating. A properly designed RCT combining H₂ inhalation with checkpoint inhibitor therapy is urgently needed.", "abstract": "It has been reported that PD-1-expressing CD8+ T cells in the peripheral blood of cancer patients are associated with poor cancer prognosis. In addition, these cells are in a state of energy shortage caused by mitochondrial dysfunction with a low level of PGC-1a. Recently, hydrogen gas was reported to activate PGC-1a, leading to the enhancement of mitochondrial activity. In the present study, we investigated whether hydrogen gas influences the proportion of PD-1+ CD8+ T cells in the peripheral blood of 55 Stage IV colorectal carcinoma patients. We found that the proportion of terminal PD-1+ CD8+ T cells was an independent factor for poor prognosis. We also found that the proportion of terminal PD-1+ CD8+ T cells was reduced in 35 out of 55 patients(63.6%)and was increased in 39 out of 55 patients(70.9%)after treatment with hydrogen gas. The ratio of the terminal PD-1+ CD8+ T cells after hydrogen gas treatment to that before hydrogen gas treatment(terminal PD-1+ CD8+ T cell ratio)was found to be an independent factor predicting PFS and OS. Out of another 26 patients treated with nivolumab, 14 patients treated with a combined therapy of hydrogen gas and nivolumab showed a significantly longer OS than the remaining 12 patients who were treated with nivolumab alone. These results suggest that hydrogen gas improves the prognosis of cancer patients by reducing the proportion of terminal PD-1+ CD8+ T cells.", "conclusion": "Out of another 26 patients treated with nivolumab, 14 patients treated with a combined therapy of hydrogen gas and nivolumab showed a significantly longer OS than the remaining 12 patients who were treated with nivolumab alone. These results suggest that hydrogen gas improves the prognosis of cancer patients by reducing the proportion of terminal PD-1+ CD8+ T cells." }, { "pmid": "30380511", "year": 2018, "title": "Protective effects of hydrogen gas against sepsis-induced acute lung injury via regulation of mitochondrial function and dynamics.", "title_en": null, "title_de": "Schützende Wirkungen von Wasserstoffgas gegen sepsis-induzierte akute Lungenschädigung über die Regulation der mitochondrialen Funktion und Dynamik", "journal": "International immunopharmacology", "authors": "Dong et al.", "author_search": "dong dong", "doi": "10.1016/j.intimp.2018.10.012", "doi_url": "https://doi.org/10.1016/j.intimp.2018.10.012", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/30380511/", "url": "https://h2medicine.org/studies/study-dong-2018-protective-against-sepsis-induced/", "methods": [ "inhalation" ], "indications": [ "cancer", "respiratory", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2018 · Dong — Protective effects of hydrogen gas against sepsis-induced acute lung injury via regulation of mitochondrial function and dynamics", "summary": "In a mouse model of sepsis-induced acute lung injury (ALI), inhaling 2% hydrogen gas improved lung oxygenation, preserved mitochondrial membrane potential and ATP production, and reduced tissue damage compared to untreated septic animals. H₂ appeared to work by normalising mitochondrial dynamics (fusion vs. fission balance). This is an animal study; results do not directly apply to humans. (International Immunopharmacology, 2018.)", "assessment": "A mechanistically well-framed animal study with consistent multi-endpoint results. The mitochondrial angle (dynamics, complex I, MFN2/Drp1) adds depth beyond simple antioxidant claims. Limitations inherent to preclinical sepsis research: CLP in inbred mouse strains does not replicate the genetic and immunological diversity of human ICU patients; no long-term survival data are reported; no dose-titration of H₂ concentration; single time-point (24 h post-CLP). Human ALI/ARDS trials with H₂ would be needed to establish clinical relevance. Results are promising for hypothesis generation but cannot be applied to human patients directly.", "abstract": "BACKGROUND: Lungs are one of the most common target organs of sepsis [1]. Hydrogen gas (H2), which has selective anti-oxidative effects, can be effectively used to treat septic mice. Mitochondrial dysfunction and dynamics play important roles in sepsis-induced organ damage. METHODS: By using cecal ligation and puncture (CLP), a classic septic model, we explored the role of 2% H2 treatment in sepsis-induced acute lung injury (ALI) linked to mitochondrial function and dynamics. We randomized male Institute for Cancer Research (ICR) mice into 4 groups: sham, sham + H2, CLP and CLP + H2. At 24 h after CLP or sham operations, we used histological examination and transmission electron microscopy (TEM) to observe lung slices. We analyzed oxygenation index (PaO2/FiO2), mitochondrial-membrane potential (MMP), adenosine triphosphate (ATP) levels, respiration control ratio (RCR) and mitochondrial-respiration complex activities (I and II) using commercial kits, and dynamin-related protein 1 (Drp1) and mitofusin-2 (MFN2) using Western blot. RESULTS: Therapy with 2% H2 increased PaO2/FiO2 ratios, MMP and ATP levels, RCR, complex I activity and MFN2 expression but decreased histological score and Drp1 levels in the presence of sepsis. These data indicated that inhalation of 2% H2 to regulate mitochondrial function and dynamics may be a promising therapeutic strategy for lung injuries induced by severe sepsis.", "conclusion": "RESULTS: Therapy with 2% H2 increased PaO2/FiO2 ratios, MMP and ATP levels, RCR, complex I activity and MFN2 expression but decreased histological score and Drp1 levels in the presence of sepsis. These data indicated that inhalation of 2% H2 to regulate mitochondrial function and dynamics may be a promising therapeutic strategy for lung injuries induced by severe sepsis." }, { "pmid": "30349057", "year": 2018, "title": "Human gut microbe co-cultures have greater potential than monocultures for food waste remediation to commodity chemicals.", "title_en": null, "title_de": "Co-Kulturen menschlicher Darmmikroben haben ein größeres Potenzial als Monokulturen für die Verwertung von Lebensmittelabfällen zu Grundchemikalien", "journal": "Scientific reports", "authors": "Perisin et al.", "author_search": "perisin perisin", "doi": "10.1038/s41598-018-33733-z", "doi_url": "https://doi.org/10.1038/s41598-018-33733-z", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/30349057/", "url": "https://h2medicine.org/studies/study-perisin-2018-gut-microbe-cultures-have/", "methods": [ "inhalation" ], "indications": [ "metabolic", "sports-exercise" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2018 · Perisin — Human gut microbe co-cultures have greater potential than monocultures for food waste remediation to commodity chemicals", "summary": "This computational study models how co-cultures of human gut bacteria convert food waste to useful chemicals (butanol, acetate, hydrogen gas, methane) more efficiently than monocultures. The hydrogen here is H₂ gas produced as a byproduct of anaerobic bacterial fermentation — not molecular hydrogen administered therapeutically. This paper is not a study of H₂ therapy and has no direct relevance to hydrogen medicine. (Scientific Reports, 2018.)", "assessment": "This paper is not relevant to H₂ therapy. It is a computational biotechnology study modelling microbial fermentation of food waste. The “hydrogen gas” mentioned is a microbial metabolic byproduct — endogenous and industrial in context — not related to drinking hydrogen-rich water, inhaling H₂, or any other therapeutic H₂ application. Its inclusion in an H₂-medicine context reflects a keyword mismatch. Methodological note: the entire study is in-silico (computational); no wet-lab validation of predicted yields is described in the abstract.", "abstract": "Food waste represents an underutilized resource for commodity chemical generation. Constituents of the human gut microbiota that are already adapted to a food waste stream could be repurposed for useful chemical production. Industrial fermentations utilizing these microbes maintain organisms in isolation; however, microbial consortia offer an attractive alternative to monocultures in that metabolic interactions may result in more efficient processes with higher yields. Here we computationally assess the ability of co-cultures vs. monocultures to anaerobically convert a Western diet to commodity chemicals. The combination of genome-scale metabolic models with flux-balance analysis predicts that every organism analyzed can benefit from interactions with another microbe, as evidenced by increased biomass fluxes in co-culture vs. monoculture. Furthermore, microbe combinations result in emergent or increased commodity chemical production including butanol, methane, formaldehyde, propionate, hydrogen gas, and urea. These overproducing co-cultures are enriched for mutualistic and commensal interactions. Using Clostridium beijerinckii co-cultures as representative examples, models predict cross-fed metabolites will simultaneously modify multiple internal pathways, evident by different internal metabolic network structures. Differences in degree and betweenness centrality of hub precursor metabolites were correlated to C. beijerinckii metabolic outputs, and thus demonstrate the potential of co-cultures to differentially direct metabolisms to useful products.", "conclusion": "Differences in degree and betweenness centrality of hub precursor metabolites were correlated to C. beijerinckii metabolic outputs, and thus demonstrate the potential of co-cultures to differentially direct metabolisms to useful products." }, { "pmid": "30120877", "year": 2018, "title": "Hydrogen Flush After Cold Storage as a New End-Ischemic Ex Vivo Treatment for Liver Grafts Against Ischemia/Reperfusion Injury.", "title_en": null, "title_de": "Wasserstoff-Spülung nach Kaltlagerung als neue ischämieendständige Ex-vivo-Behandlung von Lebertransplantaten gegen Ischämie-/Reperfusionsschädigung", "journal": "Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society", "authors": "Tamaki et al.", "author_search": "tamaki tamaki", "doi": "10.1002/lt.25326", "doi_url": "https://doi.org/10.1002/lt.25326", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/30120877/", "url": "https://h2medicine.org/studies/study-tamaki-2018-flush-after-cold-storage/", "methods": [ "unspecified" ], "indications": [ "liver", "cardiovascular", "immune-system", "oxidative-stress", "fundamentals-safety" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2018 · Tamaki — Hydrogen Flush After Cold Storage as a New End-Ischemic Ex Vivo Treatment for Liver Grafts Against Ischemia/Reperfusion Injury", "summary": "A novel ex-vivo technique — flushing rat liver grafts with hydrogen-saturated solution (1.0 ppm) after cold storage — significantly reduced ischemia/reperfusion injury markers and preserved both sinusoidal endothelia and bile duct function, compared to controls. The route of H₂ flushing mattered: portal vein flushing protected sinusoidal cells, while arterial flushing better preserved bile canaliculi. This is a rat organ-preservation study; human transplant trials are required. (Liver Transplantation, 2018.)", "assessment": "A creative and well-controlled preclinical study with a clinically motivated question. The HyFACS concept is practical, low-cost, and avoids systemic H₂ exposure issues. Route-specificity of protection is a genuinely novel mechanistic observation. Limitations: rat liver, not human; only 24 h cold storage + 2 h reperfusion — not a full transplant; no long-term graft function or survival data; H₂ concentrations and dosing will need careful optimisation for clinical application. This is promising preclinical groundwork, but human transplant organ trials are several steps away.", "abstract": "Cold storage (CS) remains the gold standard for organ preservation worldwide, although it is inevitably associated with ischemia/reperfusion injury (IRI). Molecular hydrogen (H2 ) is well known to have antioxidative properties. However, its unfavorable features, ie, inflammability, low solubility, and high tissue/substance permeability, have hampered its clinical application. To overcome such obstacles, we developed a novel reconditioning method for donor organs named hydrogen flush after cold storage (HyFACS), which is just an end-ischemic H2 flush directly to donor organs ex vivo, and, herein, we report its therapeutic impact against hepatic IRI. Whole liver grafts were retrieved from Wistar rats. After 24-hour CS in UW solution, livers were cold-flushed with H2 solution (1.0 ppm) via the portal vein (PV), the hepatic artery (HA), or both (PV + HA). Functional integrity and morphological damages were then evaluated by 2-hour oxygenated reperfusion at 37°C. HyFACS significantly lowered portal venous pressure, transaminase, and high mobility group box protein 1 release compared with vehicle-treated controls (P < 0.01). Hyaluronic acid clearance was significantly higher in the HyFACS-PV and -PV + HA groups when compared with the others (P < 0.01), demonstrating the efficacy of the PV route to maintain the sinusoidal endothelia. In contrast, bile production and lactate dehydrogenase leakage therein were both significantly improved in HyFACS-HA and -PV + HA (P < 0.01), representing the superiority of the arterial route to attenuate biliary damage. Electron microscopy consistently revealed that sinusoidal ultrastructures were well maintained by portal HyFACS, while microvilli in bile canaliculi were well preserved by arterial flush. As an underlying mechanism, HyFACS significantly lowered oxidative damages, thus improving the glutathione/glutathione disulfide ratio in liver tissue. In conclusion, HyFACS significantly protected liver grafts from IRI by ameliorating oxidative damage upon reperfusion in the characteristic manner with its route of administration. Given its safety, simplicity, and cost-effectiveness, end-ischemic HyFACS may be a novel pretransplant conditioning for cold-stored donor organs.", "conclusion": "In conclusion, HyFACS significantly protected liver grafts from IRI by ameliorating oxidative damage upon reperfusion in the characteristic manner with its route of administration. Given its safety, simplicity, and cost-effectiveness, end-ischemic HyFACS may be a novel pretransplant conditioning for cold-stored donor organs." }, { "pmid": "30096818", "year": 2018, "title": "Reducing Humidity Response of Gas Sensors for Medical Applications: Use of Spark Discharge Synthesis of Metal Oxide Nanoparticles.", "title_en": null, "title_de": "Reduzierung der Feuchtigkeitsreaktion von Gassensoren für medizinische Anwendungen: Einsatz der Funkenentladungssynthese von Metalloxid-Nanopartikeln", "journal": "Sensors (Basel, Switzerland)", "authors": "Vasiliev et al.", "author_search": "vasiliev vasiliev", "doi": "10.3390/s18082600", "doi_url": "https://doi.org/10.3390/s18082600", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/30096818/", "url": "https://h2medicine.org/studies/study-vasiliev-2018-reducing-humidity-response-sensors/", "methods": [ "unspecified" ], "indications": [ "cancer", "respiratory" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2018 · Vasiliev — Reducing Humidity Response of Gas Sensors for Medical Applications: Use of Spark Discharge Synthesis of Metal Oxide Nanoparticles", "summary": "This engineering study develops improved tin dioxide (SnO₂) nanoparticle gas sensors that are less sensitive to humidity and can detect hydrogen gas, lactate vapour, and ammonia — biomarkers respectively of gut infections, stomach cancer, and H. pylori. The H₂ here functions as a diagnostic marker detected by the sensor, not as a therapeutic agent. This is a sensor engineering study, not a hydrogen therapy study. (Sensors, 2018.)", "assessment": "This is a sensor engineering paper with no therapeutic H₂ content. Its connection to hydrogen medicine is indirect: the sensor could support exhaled-H₂ breath tests used in diagnosing gut dysbiosis or small intestinal bacterial overgrowth (SIBO) — conditions sometimes discussed in the context of gut health. However, the paper itself does not study any clinical intervention, patient population, or H₂ treatment. It is a materials science and analytical instrumentation study. Readers seeking evidence for therapeutic applications of H₂ will find nothing applicable here.", "abstract": "The application of gas sensors in breath analysis is an important trend in the early diagnostics of different diseases including lung cancer, ulcers, and enteric infection. However, traditional methods of synthesis of metal oxide gas-sensing materials for semiconductor sensors based on wet sol-gel processes give relatively high sensitivity of the gas sensor to changing humidity. The sol-gel process leading to the formation of superficial hydroxyl groups on oxide particles is responsible for the strong response of the sensing material to this factor. In our work, we investigated the possibility to synthesize metal oxide materials with reduced sensitivity to water vapors. Dry synthesis of SnO₂ nanoparticles was implemented in gas phase by spark discharge, enabling the reduction of the hydroxyl concentration on the surface and allowing the production of tin dioxide powder with specific surface area of about 40 m²/g after annealing at 610 °C. The drop in sensor resistance does not exceed 20% when air humidity increases from 40 to 100%, whereas the response to 100 ppm of hydrogen is a factor of 8 with very short response time of about 1 s. The sensor response was tested in mixtures of air with hydrogen, which is the marker of enteric infections and the marker of early stage fire, and in a mixture of air with lactate (marker of stomach cancer) and ammonia gas (marker of Helicobacter pylori, responsible for stomach ulcers).", "conclusion": "The drop in sensor resistance does not exceed 20% when air humidity increases from 40 to 100%, whereas the response to 100 ppm of hydrogen is a factor of 8 with very short response time of about 1 s. The sensor response was tested in mixtures of air with hydrogen, which is the marker of enteric infections and the marker of early stage fire, and in a mixture of air with lactate (marker of stomach c" }, { "pmid": "30041222", "year": 2018, "title": "Translational Research of Peritoneal Dialysis Solution with Dissolved Molecular Hydrogen.", "title_en": null, "title_de": "Translationale Forschung zu Peritonealdialyselösung mit gelöstem molekularem Wasserstoff", "journal": "Contributions to nephrology", "authors": "Nakayama et al.", "author_search": "nakayama nakayama", "doi": "10.1159/000485717", "doi_url": "https://doi.org/10.1159/000485717", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/30041222/", "url": "https://h2medicine.org/studies/study-nakayama-2018-translational-research-peritoneal-dialysis/", "methods": [ "saline-iv" ], "indications": [ "kidney-dialysis" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2018 · Nakayama — Translational Research of Peritoneal Dialysis Solution with Dissolved Molecular Hydrogen", "summary": "Adding molecular hydrogen to peritoneal dialysis solution (PDS) protected the peritoneal membrane in a chronic kidney disease rat model, and a small 2-week human pilot (n=6 dialysis patients) found it safe and feasible. Markers of mesothelial regeneration (CA125, mesothelin) increased in some patients, suggesting a biological effect. This is early translational research; definitive clinical evidence of benefit does not yet exist. (Contributions to Nephrology, 2018.)", "assessment": "A promising translational study that combines preclinical mechanistic data with a first-in-human feasibility signal. The peritoneal membrane is indeed at risk from long-term PDS exposure, and improved biocompatibility would be a clinically meaningful goal. Limitations: the clinical arm is n=6, uncontrolled, and very short (2 weeks); hard endpoints (technique survival, ultrafiltration capacity, EPS incidence) were not assessed; surrogate marker changes are interesting but not yet clinically validated. This work supports the rationale for larger randomised trials, but does not yet establish clinical efficacy in human dialysis patients.", "abstract": "BACKGROUND: Improved biocompatibility of peritoneal dialysis solution (PDS) is crucial for peritoneal membrane preservation, thereby ensuring long-term peritoneal dialysis (PD) and preventing encapsulating peritoneal sclerosis. We previously reported the protective effect of molecular hydrogen (H2) on mesothelial cells from PDS in nonuremic rats. SUMMARY: In the present study, we examined the effect of H2-containing PDS (commercially available neutral pH type) regarding the protection of peritoneal tissue in experimental chronic kidney disease rats. Furthermore, we conducted a 2-week clinical trial in which H2-containing PDS was used in place of standard PDS and its feasibility was examined. In the experimental study, test solutions were injected through the subcutaneous port into the abdomen for 3 weeks. Histological study revealed a significant increase in the number of mesothelial cells and a significant decrease in peritoneal thickness in the H2-PD group as compared to the control and PD groups. Also, results of immunostaining analysis revealed increased vimentin and apoptotic cells in the membrane of the PD group, indicating that H2 may play a role in ameliorating PDS-induced peritoneal injury and preserving peritoneal integrity. In the clinical trial with 6 prevalent PD patients, all subjects completed the study with no adverse effects. Moreover, there were substantial changes in surrogate markers, such as increased CA125 and mesothelin, in the effluent in selected cases, suggesting enhanced mesothelial regeneration by H2. Key Message: H2-enriched PDS is a candidate novel PDS with improved biocompatibility. Further, our results support the significance of H2-PD clinical trials in the future.", "conclusion": "Key Message: H2-enriched PDS is a candidate novel PDS with improved biocompatibility. Further, our results support the significance of H2-PD clinical trials in the future." }, { "pmid": "29923670", "year": 2018, "title": "An In Situ Depot for Continuous Evolution of Gaseous H2 Mediated by a Magnesium Passivation/Activation Cycle for Treating Osteoarthritis.", "title_en": null, "title_de": "Ein In-situ-Depot zur kontinuierlichen Entwicklung von gasförmigem H₂, vermittelt durch einen Magnesium-Passivierungs-/Aktivierungszyklus, zur Behandlung von Osteoarthrose", "journal": "Angewandte Chemie (International ed. in English)", "authors": "Wan et al.", "author_search": "wan wan", "doi": "10.1002/anie.201806159", "doi_url": "https://doi.org/10.1002/anie.201806159", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/29923670/", "url": "https://h2medicine.org/studies/study-wan-2018-situ-depot-continuous-evolution/", "methods": [ "inhalation", "saline-iv" ], "indications": [ "liver", "joints-rheumatology", "immune-system", "fundamentals-safety" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2018 · Wan — An In Situ Depot for Continuous Evolution of Gaseous H₂ Mediated by a Magnesium Passivation/Activation Cycle for Treating Osteoarthritis", "summary": "This mouse study tested intra-muscular injection of magnesium-containing microparticles (Mg@PLGA) as a local H₂ delivery system for osteoarthritis (OA). The Mg particles continuously release H₂ in body fluids via a passivation/activation cycle, sustained over time. Biochemical and histological analyses showed reduced joint inflammation and cartilage destruction in the OA mouse model. This is an animal study; no human data exist yet. (Angewandte Chemie, 2018.)", "assessment": "A creative preclinical materials science and pharmacology study with well-conceived design. The continuous-release Mg@PLGA depot concept addresses a real limitation of conventional H₂ delivery. Limitations: mouse OA model — not equivalent to human disease progression; no long-term safety data for Mg/PLGA in joints (corrosion products, inflammatory response to particles); no dose-optimisation data; no human trials. The concept is scientifically interesting and the results are encouraging, but the gap between a mouse knee injection and a human clinical application remains large. This should be considered early-stage proof-of-concept, not clinical evidence.", "abstract": "Inflammation is involved in many human pathologies, including osteoarthritis (OA). Hydrogen (H2 ) is known to have anti-inflammatory effects; however, the bioavailability of directly administered H2 gas is typically poor. Herein, a local delivery system that can provide a high therapeutic concentration of gaseous H2 at inflamed tissues is proposed. The delivery system comprises poly(lactic-co-glycolic acid) microparticles that contain magnesium powder (Mg@PLGA MPs). Mg@PLGA MPs that are intra-muscularly injected close to the OA knee in a mouse model can act as an in situ depot that can evolve gaseous H2 continuously, mediated by the cycle of passivation/activation of Mg in body fluids, at a concentration that exceeds its therapeutic threshold. The analytical data that are obtained in the biochemical and histological studies indicate that the proposed Mg@PLGA MPs can effectively mitigate tissue inflammation and prevent cartilage from destruction, arresting the progression of OA changes.", "conclusion": "Mg@PLGA MPs that are intra-muscularly injected close to the OA knee in a mouse model can act as an in situ depot that can evolve gaseous H2 continuously, mediated by the cycle of passivation/activation of Mg in body fluids, at a concentration that exceeds its therapeutic threshold. The analytical data that are obtained in the biochemical and histological studies indicate that the proposed Mg@PLGA " }, { "pmid": "29907217", "year": 2018, "title": "Hydrogen-rich water attenuates oxidative stress in rats with traumatic brain injury via Nrf2 pathway.", "title_en": null, "title_de": "Wasserstoffreiches Wasser mildert oxidativen Stress bei Ratten mit traumatischer Hirnverletzung über den Nrf2-Signalweg", "journal": "The Journal of surgical research", "authors": "Yuan et al.", "author_search": "yuan yuan", "doi": "10.1016/j.jss.2018.03.024", "doi_url": "https://doi.org/10.1016/j.jss.2018.03.024", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/29907217/", "url": "https://h2medicine.org/studies/study-yuan-2018-attenuates-oxidative-stress-rats/", "methods": [ "drinking-hrw" ], "indications": [ "neurology", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2018 · Yuan — Hydrogen-rich water attenuates oxidative stress in rats with traumatic brain injury via Nrf2 pathway", "summary": "In a rat model of traumatic brain injury (TBI), hydrogen-rich water significantly improved survival, reduced neurological deficits, and lowered oxidative stress markers. The protective mechanism appears to involve activation of the Nrf2 pathway, prompting downstream expression of protective enzymes HO-1 and NQO1. This is an animal study — results cannot be directly transferred to humans. (Journal of Surgical Research, 2018.)", "assessment": "A well-structured preclinical study with internally consistent results. This is an animal experiment — its findings cannot be extrapolated to human TBI patients without clinical trials. Rat TBI models are valuable for mechanistic insight but routinely overestimate translational success. The Nrf2-pathway narrative is plausible and aligns with other H₂ research, but the specific doses, timing windows, and H₂ concentrations used in rats may not be achievable or relevant in a clinical context. No human data exists from this paper.", "abstract": "BACKGROUND: Several studies have recently found that oxidative stress plays a pivotal role in the pathogenesis of traumatic brain injury (TBI) and may represent a target in TBI treatment. Hydrogen-rich water was recently shown to exert neuroprotective effects in various neurological diseases through its antioxidant properties. However, the mechanisms underlying its effects in TBI are not clearly understood. The purpose of our study was to evaluate the neuroprotective role of hydrogen-rich water in rats with TBI and to elucidate the possible mechanisms underlying its effects. MATERIALS AND METHODS: The TBI model was constructed according to the modified Feeney weight-drop method. In part 1 of the experiment, we measured oxidative stress levels by observing the changes in catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) expressions. We also evaluated nuclear factor erythroid 2-related factor 2 (Nrf2) levels to determine the role of the protein in the neuroprotective effects against TBI. In part 2, we verified the neuroprotective effects of hydrogen-rich water in TBI and observed its effects on Nrf2. All the experimental rats were divided into sham group, TBI group, and TBI + hydrogen-rich water-treated (TBI + HW) group. We randomly chose 20 rats from each group and recorded their 7-d survival rates. Modified neurological severity scores were recorded from an additional six rats per group, which were then sacrificed 24 h after testing. Spectrophotometry was used to measure GPx, CAT, and MDA levels, whereas western blotting, reverse transcription polymerase chain reaction, and immunohistochemistry were used to measure the expression of Nrf2 and downstream factors like heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). RESULTS: GPx and CAT activity was significantly decreased, and MDA content was increased in the TBI group compared with the sham group at 6 h after TBI. MDA content peaked at 24 h after TBI. Nrf2 nucleoprotein levels were upregulated in the TBI group compared with the sham group and peaked at 24 h after TBI; however, no significant changes in Nrf2 mRNA levels were noted after TBI. Hydrogen-rich water administration significantly increased 7-d survival rates, reduced neurologic deficits, and lowered intracellular oxidative stress levels. Moreover, hydrogen-rich water caused Nrf2 to enter the cell nucleus, which resulted in increases in the expression of downstream factors such as HO-1 and NQO1. CONCLUSIONS: Our results indicate that hydrogen-rich water has neuroprotective effects against TBI by reducing oxidative stress and activating the Nrf2 pathway.", "conclusion": "Our results indicate that hydrogen-rich water has neuroprotective effects against TBI by reducing oxidative stress and activating the Nrf2 pathway." }, { "pmid": "29901139", "year": 2018, "title": "Therapeutic efficacy of hydrogen‑rich saline alone and in combination with PI3K inhibitor in non‑small cell lung cancer.", "title_en": null, "title_de": "Therapeutische Wirksamkeit von wasserstoffreicher Kochsalzlösung allein und in Kombination mit einem PI3K-Inhibitor beim nichtkleinzelligen Lungenkarzinom", "journal": "Molecular medicine reports", "authors": "Jiang et al.", "author_search": "jiang jiang", "doi": "10.3892/mmr.2018.9168", "doi_url": "https://doi.org/10.3892/mmr.2018.9168", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/29901139/", "url": "https://h2medicine.org/studies/study-jiang-2018-therapeutic-saline-alone-combination/", "methods": [ "saline-iv" ], "indications": [ "cancer", "respiratory", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2018 · Jiang — Therapeutic efficacy of hydrogen-rich saline alone and in combination with PI3K inhibitor in non-small cell lung cancer", "summary": "In cultured human lung cancer cells (A549 line), hydrogen-rich saline reduced proliferation and promoted apoptosis; combining it with the PI3K inhibitor LY294002 enhanced these effects further by suppressing the PI3K/Akt signalling pathway. This is an in-vitro cell study — no evidence exists that this translates to human cancer patients. (Molecular Medicine Reports, 2018.)", "assessment": "This is an in-vitro study on a single cancer cell line. Results are mechanistically plausible and internally consistent, but cell culture findings in oncology routinely fail to translate to animal models, let alone humans. No animal experiments, toxicology data, or pharmacokinetic information are provided. The claim that this „may be a novel therapeutic option for patients“ is speculative at this stage. Until confirmed in rigorous preclinical models and eventually clinical trials, these findings should be understood as hypothesis-generating only.", "abstract": "The aim of the present study was to investigate the effects of combination therapy of LY294002, a specific inhibitor of phosphatidylinositol 3‑kinase (PI3K), with hydrogen‑rich saline on the proliferation and apoptosis of the non‑small cell lung cancer (NSCLC) A549 cell line and the mechanisms underpinning this. Excessive production of reactive oxygen species (ROS) may induce DNA mutations, DNA damage, genomic instability and cell proliferation, and ROS are involved in several types of cancer, particularly lung cancer. In a previous study, hydrogen was recognized as an antioxidant in preventive and therapeutic applications. The PI3K/protein kinase B (Akt) pathway is an important signaling pathway that may activate downstream of a series of extracellular signals and impact on cellular processes including cell proliferation, apoptosis and survival. To date, the PI3K/Akt signaling pathway has been indicated as a feasible target for novel antineoplastic drugs. Different strategies combining the two treatment modalities have been used in cancer therapy in order to achieve an improved therapeutic response and longer control of tumor modalities control. The present study investigated the effect of hydrogen‑rich saline alone and in combination with the PI3K inhibitor, LY294002, on the proliferation, oxidative stress and apoptosis of NSCLC A549 cells. This combination therapy may be more effective than separate drug treatment; it decreased the malondialdehyde level and increased the superoxide dismutase activity. The combination therapy also enhanced the efficacy of anti‑proliferation and apoptosis. Similarly, the results of the present study demonstrated that administration of the two agents in combination may inhibit phospho‑Akt activity, and reduce expression of heme oxygenase‑1 and nuclear factor‑κB p65. The results further suggested that the combination therapy may reduce cell proliferation and promote cell apoptosis by downregulating Akt phosphorylation and inhibiting the PI3K pathway in NSCLC cell lines. Therefore, the present study provided evidence that combined therapy may be a novel therapeutic option for patients with NSCLC.", "conclusion": "The results further suggested that the combination therapy may reduce cell proliferation and promote cell apoptosis by downregulating Akt phosphorylation and inhibiting the PI3K pathway in NSCLC cell lines. Therefore, the present study provided evidence that combined therapy may be a novel therapeutic option for patients with NSCLC." }, { "pmid": "29852353", "year": 2018, "title": "Hydrogen gas inhibits lung cancer progression through targeting SMC3.", "title_en": null, "title_de": "Wasserstoffgas hemmt das Fortschreiten von Lungenkrebs durch gezielte Beeinflussung von SMC3", "journal": "Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie", "authors": "Wang et al.", "author_search": "wang wang", "doi": "10.1016/j.biopha.2018.05.055", "doi_url": "https://doi.org/10.1016/j.biopha.2018.05.055", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/29852353/", "url": "https://h2medicine.org/studies/study-wang-2018-inhibits-lung-cancer-progression/", "methods": [ "inhalation" ], "indications": [ "cancer", "respiratory", "skin-aging" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2018 · Wang — Hydrogen gas inhibits lung cancer progression through targeting SMC3", "summary": "In lung cancer cell lines and a mouse xenograft model, hydrogen gas (H₂) inhibited cell viability, migration, and invasion while promoting apoptosis — apparently by downregulating SMC3, a chromosome condensation regulator. The tumour suppression effect in mice was weaker than cisplatin. This is a preclinical in-vitro and animal study; no human data exists. (Biomedicine & Pharmacotherapy, 2018.)", "assessment": "This is a preclinical study (cell lines + mouse xenograft). The SMC3 pathway is a novel and interesting mechanistic finding, well supported by the rescue experiment. However, the in-vivo data come from immunocompromised mice with transplanted human cell lines — a model far removed from spontaneous lung cancer in a patient. H₂ performed clearly worse than the chemotherapy agent used as comparison. No clinical conclusions can be drawn. The finding is hypothesis-generating for future mechanistic research, not a basis for therapeutic claims.", "abstract": "Lung cancer is one of the most common lethal malignancies in the globe. The patients' prognoses are dim due to its high metastatic potential and drug resistance. Therefore, in the present study, we aim to find a more potent therapeutic approach for lung cancer. We mainly explored the function of hydrogen gas (H2) on cell viability, apoptosis, migration and invasion in lung cancer cell lines A549 and H1975 by CCK-8, flow cytometry, wound healing and transwell assays, respectively. We used RNA-seq, qPCR and western blotting to detect the different expression genes (DEGs) between H2 group and control group to find the gene related to chromosome condensation. Besides, we confirmed the structural maintenance of chromosomes 3 (SMC3) and H2 on the progression of lung cancer in vitro and vivo. Results showed that H2 inhibited cell viability, migration and invasion, and catalyzed cell apoptosis and H2 induced A549 and H1975 cells G2/M arrest. Besides, H2 down-regulated the expression of NIBPL, SMC3, SMC5 and SMC6, and also reduced the expression of Cyclin D1, CDK4 and CDK6. H2 translocated the subcellular location of SMC3 during cell division and decreased its stability and increased its ubiquitination in both A549 and H1975 cells. In addition, inhibition of the proliferation, migration and invasion and promotion of the apoptosis of A549 and H1975 cells induced by H2 were all abolished when overexpressed SMC3 in the presence of H2. Animal experimental assay demonstrated that the tumor weight in H2 group was significantly smaller than that in control group, but was bigger than cis-platinum group. The expression of Ki-67, VEGF and SMC3 were decreased when mice were treated with H2 or cis-platinum, especially for cis-platinum. All data suggested that H2 inhibited lung cancer progression through down-regulating SMC3, a regulator for chromosome condensation, which provided a new method for the treatment of lung cancer.", "conclusion": "The expression of Ki-67, VEGF and SMC3 were decreased when mice were treated with H2 or cis-platinum, especially for cis-platinum. All data suggested that H2 inhibited lung cancer progression through down-regulating SMC3, a regulator for chromosome condensation, which provided a new method for the treatment of lung cancer." }, { "pmid": "29795283", "year": 2018, "title": "Positive effects of hydrogen-water bathing in patients of psoriasis and parapsoriasis en plaques.", "title_en": null, "title_de": "Positive Wirkungen von Wasserstoff-Wasser-Bädern bei Patienten mit Psoriasis und Parapsoriasis en plaques", "journal": "Scientific reports", "authors": "Zhu et al.", "author_search": "zhu zhu", "doi": "10.1038/s41598-018-26388-3", "doi_url": "https://doi.org/10.1038/s41598-018-26388-3", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/29795283/", "url": "https://h2medicine.org/studies/study-zhu-2018-positive-bathing-psoriasis-parapsoriasis/", "methods": [ "bath-topical", "drinking-hrw" ], "indications": [ "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2018 · Zhu — Positive Effects of Hydrogen-Water Bathing in Patients of Psoriasis and Parapsoriasis en Plaques", "summary": "In a parallel-controlled trial, hydrogen-water bathing achieved at least 75% improvement in psoriasis severity (PASI-75) in 24.4% of patients versus 2.9% in controls, with over half the patients reaching PASI-50 improvement. This is one of the few controlled H₂ studies in dermatology, targeting chronic inflammatory skin disease via topical H₂ exposure. (Scientific Reports, 2018.)", "assessment": "A clinically relevant controlled study in an indication with real unmet need. Published in a peer-reviewed Nature group journal. The PASI-75 benchmark gives this study contextual comparison with established psoriasis therapies. Limitations: the study is not blinded — it is difficult to blind patients to hydrogen-water bathing vs. regular water bathing; total n = 75 (41 treatment, 34 control) is modest; the H₂ concentration of the bath water and the bathing protocol (frequency, duration, water temperature) are not detailed in the available abstract; the parapsoriasis sub-analysis involves only 6 patients and is purely descriptive; no long-term follow-up data. The results are sufficiently strong to justify a larger, ideally sham-controlled trial.", "abstract": "Psoriasis and parapsoriasis en plaques are chronic inflammatory skin diseases, both representing therapeutic challenge in daily practice and adversely affecting the quality of life. Reactive oxygen species (ROS) has been evidenced to be involved in the pathogenesis of the chronic inflammatory diseases. We now report that hydrogen water, an effective ROS scavenger, has significant and rapid improvement in disease severity and quality of life for patients with psoriasis and parapsoriasis en plaques. At week 8, our parallel-controlled trial revealed 24.4% of patients (10/41) receiving hydrogen-water bathing achieved at least 75% improvement in Psoriasis Area Severity Index (PASI) score compared with 2.9% of patients (1/34) of the control group (Pc = 0.022, OR = 0.094, 95%CI = [0.011, 0.777]). Of patients, 56.1% (23/41) who received bathing achieved at least 50% improvement in PASI score compared with only 17.7%(6/34) of the control group (P = 0.001, OR = 0.168, 95%CI = [0.057, 0.492]). The significant improvement of pruritus was also observed (P = 3.94 × 10-4). Besides, complete response was observed in 33.3% of patients (2/6) of parapsoriasis en plaques and partial response in 66.7% (4/6) at week 8. Our findings suggested that hydrogen-water bathing therapy could fulfill the unmet need for these chronic inflammatory skin diseases.", "conclusion": "Besides, complete response was observed in 33.3% of patients (2/6) of parapsoriasis en plaques and partial response in 66.7% (4/6) at week 8. Our findings suggested that hydrogen-water bathing therapy could fulfill the unmet need for these chronic inflammatory skin diseases." }, { "pmid": "29779270", "year": 2018, "title": "[Protective effects of hydrogen-rich medium on lipopolysaccharides-induced injury in human periodontal ligament cells].", "title_en": null, "title_de": "Schützende Wirkungen von wasserstoffreichem Medium auf lipopolysaccharid-induzierte Schädigung in menschlichen Parodontalligamentzellen", "journal": "Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology", "authors": "Zhou et al.", "author_search": "zhou zhou", "doi": "10.7518/hxkq.2018.02.002", "doi_url": "https://doi.org/10.7518/hxkq.2018.02.002", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/29779270/", "url": "https://h2medicine.org/studies/study-zhou-2018-protective-medium-lipopolysaccharides-induced/", "methods": [ "unspecified" ], "indications": [ "oral-health", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2018 · Zhou — Protective effects of hydrogen-rich medium on lipopolysaccharide-induced injury in human periodontal ligament cells", "summary": "In cultured human periodontal ligament cells (hPDLCs) exposed to lipopolysaccharide (LPS) to simulate bacterial inflammation, hydrogen-rich medium improved cell proliferation, reduced apoptosis, and lowered oxidative stress markers. This is a cell culture study — results cannot be applied directly to clinical periodontitis treatment. (West China Journal of Stomatology, 2018.)", "assessment": "This is an in-vitro cell study. The results suggest a partial protective effect of H₂ on periodontal ligament cells under LPS stress, but the null results for SOD and LDH mean the protection is not comprehensive. No animal or clinical periodontal data are provided. The findings are preliminary and relevant primarily for guiding future preclinical research into H₂ and oral health. No treatment conclusions should be drawn.", "abstract": "OBJECTIVE: In this study, lipopolysaccharides (LPS) was used to damage human periodontal ligament cells (hPDLCs) and consequently investigate the protective effects of hydrogen on reducing oxidative stress and cell apoptosis rate. METHODS: hPDLCs were isolated, and then cultured with normal medium+1 μg·mL⁻¹ LPS or with hydrogen-rich medium+
1 μg·mL⁻¹ LPS. Cell proliferation activity was assessed using a cell counting kit-8 (CCK-8), and lactic dehydrogenase (LDH) release was also detected. The activities of superoxide dismutase (SOD) and catalase (CAT), and the level of malonaldehyde (MDA) in supernatants were also measured. Cell apoptosis was detected by flow cytometry at 24 h after LPS stimulation. RESULTS: CCK-8 results showed that hydrogen could significantly improve hPDLCs growth and decrease cell apoptosis under LPS stimulation (P<0.05). However, no significant difference in LDH release was found between the two groups. The CAT levels significantly increased at 6 and 12 h in the hydrogen-rich medium as compared with the normal medium group (P<0.05, P<0.01, respectively). However, SOD levels were not significant different at each time point. At 6 h after LPS stimulation, the MDA levels in the cell supernatant of hydrogen-rich medium group were significantly reduced as compared with those in the normal medium group (P<0.05). CONCLUSIONS: The hydrogen-rich medium can effectively improve hPDLCs proliferation activity and antioxidant capacity and reduce apoptosis and oxidative stress under LPS stimulation.", "conclusion": "The hydrogen-rich medium can effectively improve hPDLCs proliferation activity and antioxidant capacity and reduce apoptosis and oxidative stress under LPS stimulation." }, { "pmid": "29712968", "year": 2018, "title": "Lignite coal burning seam in the remote Altai Mountains harbors a hydrogen-driven thermophilic microbial community.", "title_en": null, "title_de": "Ein brennender Braunkohleflöz in den abgelegenen Altai-Bergen beherbergt eine wasserstoffgetriebene thermophile mikrobielle Gemeinschaft", "journal": "Scientific reports", "authors": "Kadnikov et al.", "author_search": "kadnikov kadnikov", "doi": "10.1038/s41598-018-25146-9", "doi_url": "https://doi.org/10.1038/s41598-018-25146-9", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/29712968/", "url": "https://h2medicine.org/studies/study-kadnikov-2018-lignite-coal-burning-seam/", "methods": [ "unspecified" ], "indications": [ "sports-exercise", "cancer" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2018 · Kadnikov — Lignite coal burning seam in the remote Altai Mountains harbors a hydrogen-driven thermophilic microbial community", "summary": "In an underground coal fire site in the Altai Mountains, researchers identified thermophilic bacteria that survive by oxidising molecular hydrogen produced during coal combustion. This is a basic microbiology and geomicrobiology study — it has no direct relevance to H₂ medicine or human health. (Scientific Reports, 2018.)", "assessment": "This study has no relevance to human H₂ medicine. It is a geomicrobiology paper about bacteria living in a coal-fire ecosystem. It is included here for completeness of the literature database, but contains no data on H₂ supplementation, human biology, disease, or therapy. No health-related conclusions of any kind can be drawn from it.", "abstract": "Thermal ecosystems associated with underground coal combustion sites are rare and less studied than geothermal features. Here we analysed microbial communities of near-surface ground layer and bituminous substance in an open quarry heated by subsurface coal fire by metagenomic DNA sequencing. Taxonomic classification revealed dominance of only a few groups of Firmicutes. Near-complete genomes of three most abundant species, 'Candidatus Carbobacillus altaicus' AL32, Brockia lithotrophica AL31, and Hydrogenibacillus schlegelii AL33, were assembled. According to the genomic data, Ca. Carbobacillus altaicus AL32 is an aerobic heterotroph, while B. lithotrophica AL31 is a chemolithotrophic anaerobe assimilating CO2 via the Calvin cycle. H. schlegelii AL33 is an aerobe capable of both growth on organic compounds and carrying out CO2 fixation via the Calvin cycle. Phylogenetic analysis of the large subunit of RuBisCO of B. lithotrophica AL31 and H. schlegelii AL33 showed that it belongs to the type 1-E. All three Firmicutes species can gain energy from aerobic or anaerobic oxidation of molecular hydrogen, produced as a result of underground coal combustion along with other coal gases. We propose that thermophilic Firmicutes, whose spores can spread from their original geothermal habitats over long distances, are the first colonizers of this recently formed thermal ecosystem.", "conclusion": "All three Firmicutes species can gain energy from aerobic or anaerobic oxidation of molecular hydrogen, produced as a result of underground coal combustion along with other coal gases. We propose that thermophilic Firmicutes, whose spores can spread from their original geothermal habitats over long distances, are the first colonizers of this recently formed thermal ecosystem." }, { "pmid": "29532858", "year": 2018, "title": "Hydrogen ameliorates oxidative stress via PI3K-Akt signaling pathway in UVB-induced HaCaT cells.", "title_en": null, "title_de": "Wasserstoff mildert oxidativen Stress über den PI3K-Akt-Signalweg in UVB-induzierten HaCaT-Zellen", "journal": "International journal of molecular medicine", "authors": "Zhang et al.", "author_search": "zhang zhang", "doi": "10.3892/ijmm.2018.3550", "doi_url": "https://doi.org/10.3892/ijmm.2018.3550", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/29532858/", "url": "https://h2medicine.org/studies/study-zhang-2018-ameliorates-oxidative-stress-pi3k/", "methods": [ "unspecified" ], "indications": [ "cancer", "skin-aging", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2018 · Zhang — Hydrogen ameliorates oxidative stress via PI3K-Akt signalling pathway in UVB-induced HaCaT cells", "summary": "In human keratinocyte cells (HaCaT line) irradiated with UVB, hydrogen treatment reduced reactive oxygen species and oxidative damage markers while activating the PI3K/Akt/Nrf2/HO-1 protective cascade. This is an in-vitro study on skin cells — not a clinical study in humans, and no sun-protection or anti-ageing claims can be derived from it. (International Journal of Molecular Medicine, 2018.)", "assessment": "This is an in-vitro cell study on a keratinocyte cell line. The mechanistic findings are interesting and internally consistent for the most part, though the conclusion's phrasing has an apparent contradiction regarding pathway „inhibition“ vs. activation. In any case, HaCaT cells in culture do not replicate the complexity of living human skin — thickness, immune cells, blood supply, melanocytes, repair mechanisms. No clinical sun-damage or skin-health conclusions can be drawn.", "abstract": "Chronic ultraviolet (UV) exposure-induced oxidative stress is associated with the pathogenesis of skin damage. However, the nuclear factor erythroid‑2‑related factor 2 (Nrf2) pathway is a critical factor in protecting cells against UVB‑induced injury through inhibiting oxidative stress. Furthermore, Nrf2 activation requires the involvement of the phosphoinositide-3 kinase (PI3K)/protein kinase B (AKT) pathway, which has a major role in survival of various cell types. Molecular hydrogen exerts protective effects on UV‑induced injury, but the underlying mechanisms have remained elusive. The present study assessed the protective effects of hydrogen against oxidative stress‑induced injury caused by UVB irradiation and investigated the molecular mechanisms. In vitro, UVB‑induced HaCaT cells were collected for the detection of reactive oxygen species, 8‑iso‑prostaglandin F2α, malondialdehyde via fluorescence spectrometry and ELISA; cell activity and cytotoxicity by MTT and lactate dehydrogenase assays, respectively. Additionally, the expression level of PI3K, Akt, Nrf2 and heme oxygenase‑1 (HO‑1) were investigated using western blot, etc. All of the results indicated that hydrogen decreased the levels of reactive oxygen species, 8‑iso‑prostaglandin F2α and malondialdehyde, and promoted the UVB exposure‑induced expression of PI3K, Akt, Nrf2 and heme oxygenase‑1 in HaCaT cells. Of note, PI3K inhibition partially reversed the effects of hydrogen on UVB‑induced HaCaT cells. Therefore, hydrogen effectively protects cells from UVB radiation‑induced oxidative stress by inhibiting Nrf2/HO‑1 activation through the PI3K/Akt signaling pathway.", "conclusion": "Of note, PI3K inhibition partially reversed the effects of hydrogen on UVB‑induced HaCaT cells. Therefore, hydrogen effectively protects cells from UVB radiation‑induced oxidative stress by inhibiting Nrf2/HO‑1 activation through the PI3K/Akt signaling pathway." }, { "pmid": "29532225", "year": 2018, "title": "A molecular dynamics approach to explore the structural characterization of cataract causing mutation R58H on human γD crystallin.", "title_en": null, "title_de": "Ein molekulardynamischer Ansatz zur Untersuchung der strukturellen Charakterisierung der katarakt-verursachenden Mutation R58H im menschlichen γD-Crystallin", "journal": "Molecular and cellular biochemistry", "authors": "Karunakaran et al.", "author_search": "karunakaran karunakaran", "doi": "10.1007/s11010-018-3342-8", "doi_url": "https://doi.org/10.1007/s11010-018-3342-8", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/29532225/", "url": "https://h2medicine.org/studies/study-karunakaran-2018-dynamics-approach-explore-structural/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2018 · Karunakaran — A molecular dynamics approach to explore the structural characterisation of cataract causing mutation R58H on human γD crystallin", "summary": "Using molecular dynamics simulations, researchers modelled how the R58H mutation in γD-crystallin — a lens protein — promotes protein misfolding and aggregation, potentially causing cataract. This is a computational protein-structure study with no connection to hydrogen medicine or H₂ therapy. (Molecular and Cellular Biochemistry, 2018.)", "assessment": "This paper has no relevance to H₂ medicine. It is a computational biophysics study about a cataract-associated lens protein mutation. The word „hydrogen“ in this context refers exclusively to hydrogen bonds between atoms in the protein — not molecular hydrogen (H₂). It is included for completeness of the literature record but contains no information about H₂ supplementation, antioxidant hydrogen, or human health benefits of H₂. No health conclusions of any kind can be drawn.", "abstract": "The crystallins are a family of monomeric proteins present in the mammalian lens and mutations in these proteins cause various forms of cataracts. The aim of our current study is to emphasize the structural characterization of aggregation propensity of mutation R58H on γD crystallin using molecular dynamics (MD) approach. MD result revealed that difference in the sequence level display a wide variation in the backbone atomic position, and thus exhibits rigid conformational dynamics. Changes in the flexibility of residues favoured to increase the number of intra-molecular hydrogen bonds in mutant R58H. Moreover, notable changes in the hydrogen bonding interaction resulted to cause the misfolding of mutant R58H by introducing α-helix. Principal component analysis (PCA) result suggested that mutant R58H showed unusual conformational dynamics along the two principal components when compared to the wild-type (WT)-γD crystallin. In a nutshell, the increased surface hydrophobicity could be the cause of self-aggregation of mutant R58H leading to aculeiform cataract.", "conclusion": "Principal component analysis (PCA) result suggested that mutant R58H showed unusual conformational dynamics along the two principal components when compared to the wild-type (WT)-γD crystallin. In a nutshell, the increased surface hydrophobicity could be the cause of self-aggregation of mutant R58H leading to aculeiform cataract." }, { "pmid": "29512923", "year": 2018, "title": "Modulation of the oxidative plasmatic state in gastroesophageal reflux disease with the addition of rich water molecular hydrogen: A new biological vision.", "title_en": null, "title_de": "Modulation des oxidativen Plasmazustands bei gastroösophagealer Refluxkrankheit durch Zusatz von molekular-wasserstoffreichem Wasser: Eine neue biologische Sichtweise", "journal": "Journal of cellular and molecular medicine", "authors": "Franceschelli et al.", "author_search": "franceschelli franceschelli", "doi": "10.1111/jcmm.13569", "doi_url": "https://doi.org/10.1111/jcmm.13569", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/29512923/", "url": "https://h2medicine.org/studies/study-franceschelli-2018-modulation-oxidative-plasmatic-state/", "methods": [ "unspecified" ], "indications": [ "cardiovascular", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2018 · Franceschelli — Modulation of the Oxidative Plasmatic State in Gastroesophageal Reflux Disease with the Addition of Hydrogen-Rich Water: A New Biological Vision", "summary": "In 84 patients with gastroesophageal reflux disease (GERD), adding electrolyzed reduced water rich in molecular hydrogen to standard proton pump inhibitor therapy significantly improved both oxidative stress markers and GERD-related quality of life versus PPI alone. This study positions H₂ as a complementary, not standalone, GERD intervention. (Journal of Cellular and Molecular Medicine, 2018.)", "assessment": "A mechanistically grounded and clinically well-designed study with a meaningful primary outcome (QoL in GERD) supported by laboratory correlates. Published in a peer-reviewed molecular medicine journal (Wiley). Limitations: the H₂ delivery method (ERW — electrolyzed reduced water) carries the same caveats as in other ERW studies: the H₂ concentration is not specified; ERW contains other components (mineral ions, adjusted pH) that could theoretically contribute; the study design is not explicitly randomized and blinded — „control vs. experimental treatment“ allocation details are limited in the abstract; n = 84 is modest for a 3-month controlled study; the „unspecified“ methods flag in the source data suggests the H₂ delivery details may be incomplete. Results are promising but deserve replication with better-characterized H₂ delivery.", "abstract": "Gastroesophageal reflux disease (GERD), a clinical condition characterized by reflux of gastroduodenal contents in the oesophagus, has proved to demonstrate a strong link between oxidative stress and the development of GERD. Proton pump inhibitors (PPIs) have been universally accepted as first-line therapy for management of GERD. The potential benefits of electrolysed reduced water (ERW), rich in molecular hydrogen, in improving symptoms and systemic oxidative stress associated with GERD was assessed. The study was performed on 84 GERD patients undergoing control treatment (PPI + tap water) or experimental treatment (PPI + ERW) for 3 months. These patients were subjected to the GERD-Health Related Quality of Life Questionnaire as well as derivatives reactive oxigen metabolites (d-ROMs) test, biological antioxidant potential (BAP) test, superoxide anion, nitric oxide and malondialdehyde assays, which were all performed as a proxy for the oxidative/nitrosative stress and the antioxidant potential status. Spearman's correlation coefficient was used to evaluate the correlation between scores and laboratory parameters. Overall results demonstrated that an optimal oxidative balance can be restored and GERD symptoms can be reduced rapidly via the integration of ERW in GERD patients. The relative variation of heartburn and regurgitation score was significantly correlated with laboratory parameters. Thus, in the selected patients, combination treatment with PPI and ERW improves the cellular redox state leading to the improvement of the quality of life as demonstrated by the correlation analysis between laboratory parameters and GERD symptoms.", "conclusion": "The relative variation of heartburn and regurgitation score was significantly correlated with laboratory parameters. Thus, in the selected patients, combination treatment with PPI and ERW improves the cellular redox state leading to the improvement of the quality of life as demonstrated by the correlation analysis between laboratory parameters and GERD symptoms." }, { "pmid": "29478695", "year": 2018, "title": "Inadequate Production of H2 by Gut Microbiota and Parkinson Disease.", "title_en": null, "title_de": "Unzureichende Produktion von H₂ durch die Darmmikrobiota und Morbus Parkinson", "journal": "Trends in endocrinology and metabolism: TEM", "authors": "Ostojic", "author_search": "ostojic ostojic", "doi": "10.1016/j.tem.2018.02.006", "doi_url": "https://doi.org/10.1016/j.tem.2018.02.006", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/29478695/", "url": "https://h2medicine.org/studies/study-ostojic-2018-inadequate-production-gut-microbiota/", "methods": [ "drinking-hrw" ], "indications": [ "neurology", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2018 · Ostojic — Inadequate Production of H₂ by Gut Microbiota and Parkinson Disease", "summary": "This theoretical paper proposes that impaired H₂ production by intestinal bacteria may contribute to the development of Parkinson's disease, and discusses supplemental H₂ as a potential therapeutic direction. This is a speculative, hypothesis-driven review — not an experimental study, and no clinical conclusions can be drawn. (Trends in Endocrinology and Metabolism, 2018.)", "assessment": "This is a theoretical perspective paper — no experiment, no clinical data, no new measurements. The hypothesis (gut microbiota H₂ → neuroprotection → PD risk) is mechanistically plausible and worth investigating, and aligns with the general direction of gut-brain-axis and H₂ research. However, it remains unproven. The observation that PD patients have altered gut microbiomes does not establish that reduced H₂ production is causally involved. This paper should be read as a research agenda, not as evidence of efficacy.", "abstract": "Dysbiosis of the gut flora accompanies Parkinson disease (PD), yet no specific cause-effect link has been identified so far. The gut microbiota produce molecular hydrogen (H2), a ubiquitous molecule recently recognized as a biologically active gas with antioxidant, antiapoptotic, anti-inflammatory, cytoprotective, and signaling properties. Here, we discuss an idea that an impaired production of endogenous H2 by intestinal microbiota might play a role in PD pathogenesis, with supplemental H2 debated as a possible therapy for this progressive neurodegenerative disease.", "conclusion": "The gut microbiota produce molecular hydrogen (H2), a ubiquitous molecule recently recognized as a biologically active gas with antioxidant, antiapoptotic, anti-inflammatory, cytoprotective, and signaling properties. Here, we discuss an idea that an impaired production of endogenous H2 by intestinal microbiota might play a role in PD pathogenesis, with supplemental H2 debated as a possible therapy" }, { "pmid": "29321509", "year": 2018, "title": "Novel haemodialysis (HD) treatment employing molecular hydrogen (H2)-enriched dialysis solution improves prognosis of chronic dialysis patients: A prospective observational study.", "title_en": null, "title_de": "Neuartige Hämodialyse-Behandlung mit einer mit molekularem Wasserstoff angereicherten Dialyselösung verbessert die Prognose chronischer Dialysepatienten: Eine prospektive Beobachtungsstudie", "journal": "Scientific reports", "authors": "Nakayama et al.", "author_search": "nakayama nakayama", "doi": "10.1038/s41598-017-18537-x", "doi_url": "https://doi.org/10.1038/s41598-017-18537-x", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/29321509/", "url": "https://h2medicine.org/studies/study-nakayama-2018-haemodialysis-employing-enriched-dialysis/", "methods": [ "unspecified" ], "indications": [ "liver", "cardiovascular", "kidney-dialysis", "immune-system" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2018 · Nakayama — Novel Haemodialysis Treatment Employing Molecular Hydrogen-Enriched Dialysis Solution Improves Prognosis of Chronic Dialysis Patients: A Prospective Observational Study", "summary": "Over a mean observation period of 3.28 years, chronic haemodialysis patients treated with H₂-enriched dialysis solution had a 41% lower risk of combined all-cause mortality and major cardiovascular events compared to conventional haemodialysis (hazard ratio 0.59, 95% CI 0.38–0.92). This is one of the largest and longest H₂ outcome studies in a high-risk patient population. (Scientific Reports, 2018.)", "assessment": "This is one of the most impressive H₂ clinical studies in terms of outcome relevance — a 41% hazard reduction in all-cause mortality plus cardiovascular events over 3+ years in a high-risk population is clinically meaningful if valid. Published in Scientific Reports (Nature group). Limitations: this is a non-randomized, non-blinded observational study — allocation to E-HD vs. C-HD was not random, and residual confounding cannot be excluded despite the multivariate adjustment; both groups received identical dialysis protocols except for H₂, but baseline differences between groups are not fully described; 30–80 ppb H₂ is a relatively low concentration compared to drinking water studies; the study is from a single research group in Japan. These limitations mean this study, while compelling, cannot be considered proof of causal efficacy — a randomized controlled trial is urgently needed to confirm this result.", "abstract": "Recent studies have revealed unique biological characteristics of molecular hydrogen (H2) as an anti-inflammatory agent. We developed a novel haemodialysis (E-HD) system delivering an H2 (30-80 ppb)-enriched dialysis solution by water electrolysis, and conducted a non-randomized, non-blinded, prospective observational study exploring its clinical impact. Prevalent chronic HD patients were allocated to either the E-HD (n = 161) group or the conventional HD (C-HD: n = 148) group, and received the respective HD treatments during the study. The primary endpoint was a composite of all-cause mortality and development of non-lethal cardio-cerebrovascular events (cardiac disease, apoplexy, and leg amputation due to peripheral artery disease). During the 3.28-year mean observation period, there were no differences in dialysis parameters between the two groups; however, post-dialysis hypertension was ameliorated with significant reductions in antihypertensive agents in the E-HD patients. There were 91 events (50 in the C-HD group and 41 in the E-HD group). Multivariate analysis of the Cox proportional hazards model revealed E-HD as an independent significant factor for the primary endpoint (hazard ratio 0.59; [95% confidence interval: 0.38-0.92]) after adjusting for confounding factors (age, cardiovascular disease history, serum albumin, and C-reactive protein). HD applying an H2-dissolved HD solution could improve the prognosis of chronic HD patients.", "conclusion": "Multivariate analysis of the Cox proportional hazards model revealed E-HD as an independent significant factor for the primary endpoint (hazard ratio 0.59; [95% confidence interval: 0.38-0.92]) after adjusting for confounding factors (age, cardiovascular disease history, serum albumin, and C-reactive protein). HD applying an H2-dissolved HD solution could improve the prognosis of chronic HD patien" }, { "pmid": "28474871", "year": 2018, "title": "Effects of hydrogen rich water on prolonged intermittent exercise.", "title_en": null, "title_de": "Wirkungen von wasserstoffreichem Wasser auf verlängerte intermittierende Belastung", "journal": "The Journal of sports medicine and physical fitness", "authors": "Da Ponte et al.", "author_search": "da ponte da ponte", "doi": "10.23736/s0022-4707.17.06883-9", "doi_url": "https://doi.org/10.23736/s0022-4707.17.06883-9", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/28474871/", "url": "https://h2medicine.org/studies/study-daponte-2018-prolonged-intermittent-exercise/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise", "cardiovascular" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2018 · Da Ponte — Effects of Hydrogen-Rich Water on Prolonged Intermittent Exercise", "summary": "Two weeks of hydrogen-rich water intake helped trained cyclists maintain peak power output during repeated all-out sprints over 30 minutes — where the placebo group showed significant power decline in the later sprints. This crossover study adds controlled evidence to H₂'s role in sustaining high-intensity exercise performance. (The Journal of Sports Medicine and Physical Fitness, 2018.)", "assessment": "A well-designed crossover study with a specific and objective performance outcome (PPO maintenance). The placebo-controlled, crossover design with randomized sequence and trained athletes is methodologically sound. Limitations: n = 8 is very small — a crossover design partially compensates for this, but statistical power is still limited; only male cyclists aged 41±7 years — results may not generalize to other populations or sports; the study is single-blind (investigator blinded, but the distinctive pH and ORP of HRW vs. placebo may have allowed athletes to distinguish them by taste); the mechanism remains unclear (acid-base parameters were similar in both groups); no data on H₂ absorption or systemic H₂ levels were measured. The PPO maintenance finding is the most practically relevant result, but replication in a larger cohort is needed.", "abstract": "BACKGROUND: Recent studies showed a positive effect of hydrogen rich water (HRW) intake on acid-base homeostasis at rest. We investigated 2-weeks of HRW intake on repeated sprint performance and acid-base status during prolonged intermittent cycling exercise. METHODS: In a cross over single-blind protocol, 8 trained male cyclists (age [mean±SD] 41±7 years, body mass 72.3±4.4 kg, height 1.77±0.04 m, maximal oxygen uptake [V̇O2max] 52.6±4.4 mL·kg-1·min-1) were provided daily with 2 liters of placebo normal water (PLA, pH 7.6, oxidation/reduction potential [ORP] +230 mV, free hydrogen content 0 ppb) or HRW (pH 9.8, ORP -180 mV, free Hydrogen 450 ppb). Tests were performed at baseline and after each period of 2 weeks of treatment. The treatments were counter-balanced and the sequence randomized. The 30-minute intermittent cycling trial consisted in 10 3-minute blocks, each one composed by 90 seconds at 40% V̇O2max, 60 seconds at 60% V̇O2max, 16 seconds all out sprint, and 14 seconds active recovery. Oxygen uptake (V̇O2), heart rate and power output were measured during the whole test, while mean and peak power output (PPO), time to peak power and Fatigue Index (FI) were determined during all the 16 seconds sprints. Lactate, pH and bicarbonate (HCO3-) concentrations were determined at rest and after each sprint on blood obtained by an antecubital vein indwelling catheter. RESULTS: In the PLA group, PPO in absolute values decreased significantly at the 8th and 9th of 10 sprints and in relative values, ΔPPO, decreased significantly at 6th, 8th and 9th of 10 sprints (by mean: -12±5%, P<0.006), while it remained unchanged in HRW group. Mean power, FI, time to peak power and total work showed no differences between groups. In both conditions lactate levels increased while pH and HCO3- decreased progressively as a function of the number of sprints. CONCLUSIONS: Two weeks of HRW intake may help to maintain PPO in repetitive sprints to exhaustion over 30 minutes.", "conclusion": "Two weeks of HRW intake may help to maintain PPO in repetitive sprints to exhaustion over 30 minutes." }, { "pmid": "27281176", "year": 2017, "title": "Molecular Hydrogen as a Neuroprotective Agent", "title_en": null, "title_de": "Molekularer Wasserstoff als neuroprotektives Agens", "journal": "Current Neuropharmacology", "authors": "Iketani et al.", "author_search": "iketani iketani", "doi": "10.2174/1570159x14666160607205417", "doi_url": "https://doi.org/10.2174/1570159x14666160607205417", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/27281176/", "url": "https://h2medicine.org/studies/study-iketani-2017-neuroprotective-agent/", "methods": [ "inhalation", "saline-iv", "drinking-hrw" ], "indications": [ "neurology", "fundamentals", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2017 · Iketani — Molecular Hydrogen as a Neuroprotective Agent", "summary": "Molecular hydrogen (H₂) acts as an antioxidant and anti-inflammatory agent and shows potential in neurological disorders — from stroke through neurodegenerative diseases to brain damage in newborns. (Review by Iketani & Ohsawa, Current Neuropharmacology, 2017.)", "assessment": "A valuable, well-cited review from a pioneering author group (Ohsawa) — ideal for documenting the breadth of neurological H₂ research, including drinking H₂ water as a route of administration. This makes it a useful context source for the field. Limitations, stated honestly: a pure review (evidence level 4), no own patient data, and the authors deliberately phrase things cautiously („clinical potential“, „incurable“) — they openly admit that the direct molecular target of H₂ is not yet known. No proof of a cure for neurological diseases, but a survey of the potential.", "abstract": "Oxidative stress and neuroinflammation cause many neurological disorders. Recently, it has been reported that molecular hydrogen (H2) functions as an antioxidant and anti-inflammatory agent. The routes of H2 administration in animal model and human clinical studies are roughly classified into three types, inhalation of H2 gas, drinking H2-dissolved water, and injection of H2-dissolved saline. This review discusses some of the remarkable progress that has been made in the research of H2 use for neurological disorders, such as cerebrovascular diseases, neurodegenerative disorders, and neonatal brain disorders. Although most neurological disorders are currently incurable, these studies suggest the clinical potential of H2 administration for their prevention, treatment, and mitigation. Several of the potential effectors of H2 will also be discussed, including cell signaling molecules and hormones that are responsible for preventing oxidative stress and inflammation. Nevertheless, further investigation will be required to determine the direct target molecule of H2.", "conclusion": "Several of the potential effectors of H2 will also be discussed, including cell signaling molecules and hormones that are responsible for preventing oxidative stress and inflammation. Nevertheless, further investigation will be required to determine the direct target molecule of H2." }, { "pmid": "29058596", "year": 2017, "title": "Efficacy of inhaled HYdrogen on neurological outcome following BRain Ischemia During post-cardiac arrest care (HYBRID II trial): study protocol for a randomized controlled trial.", "title_en": null, "title_de": "Wirksamkeit von inhaliertem Wasserstoff auf das neurologische Ergebnis nach Hirnischämie während der Versorgung nach Herzstillstand (HYBRID-II-Studie): Studienprotokoll für eine randomisierte kontrollierte Studie", "journal": "Trials", "authors": "Tamura et al.", "author_search": "tamura tamura", "doi": "10.1186/s13063-017-2246-3", "doi_url": "https://doi.org/10.1186/s13063-017-2246-3", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/29058596/", "url": "https://h2medicine.org/studies/study-tamura-2017-inhaled-neurological-outcome-following/", "methods": [ "inhalation" ], "indications": [ "sports-exercise", "neurology", "fundamentals-safety" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2017 · Tamura — Efficacy of Inhaled Hydrogen on Neurological Outcome Following Brain Ischemia During Post-Cardiac Arrest Care (HYBRID II Trial): Study Protocol for a Randomized Controlled Trial", "summary": "This is the published protocol for the HYBRID II trial — a multicenter, randomized, double-blind, placebo-controlled trial designed to enroll 360 comatose cardiac arrest survivors and evaluate whether 18 hours of 2% hydrogen inhalation improves 90-day neurological outcome. The trial represents the highest-quality evidence infrastructure for H₂ in post-cardiac arrest care. (Trials, 2017.)", "assessment": "This publication is a study protocol, not results — its value lies in confirming that a properly powered, well-designed RCT for H₂ in cardiac arrest was initiated. The protocol design is exemplary: multicenter, randomized, double-blinded, pre-registered, adequately powered, clinically meaningful primary outcome. Limitations of the protocol paper: no efficacy data is available from this publication; the feasibility of blinding H₂ vs. oxygen inhalation in an intensive care setting is challenging (though feasible with identical-appearing gas mixtures); 18 hours of H₂ inhalation during mechanical ventilation is logistically complex and limits applicability to well-equipped centers. The actual trial results from HYBRID II should be sought in subsequent publications for a complete picture of H₂ in post-cardiac arrest neuroprotection.", "abstract": "BACKGROUND: Hydrogen gas inhalation (HI) improved survival and neurological outcomes in an animal model of post-cardiac arrest syndrome (PCAS). The feasibility and safety of HI for patients with PCAS was confirmed in a pilot study. The objective of this study is to evaluate the efficacy of HI for patients with PCAS. METHODS/DESIGN: The efficacy of inhaled HYdrogen on neurological outcome following BRain Ischemia During post-cardiac arrest care (HYBRID II) trial is an investigator-initiated, randomized, double-blind, placebo-controlled trial designed to enroll 360 adult comatose (Glasgow Coma Scale score < 8) patients who will be resuscitated following an out-of-hospital cardiac arrest of a presumed cardiac cause. The patients will be randomized (1:1) to either the HI or control group. Patients in the HI group will inhale 2% hydrogen with 24% to 50% oxygen, and those in the control group will inhale 24% to 50% oxygen for 18 h after admission via mechanical ventilation. Multidisciplinary post-arrest care, including targeted temperature management (TTM) between 33 °C and 36 °C, will be provided in accordance with the latest guidelines. The primary outcome of interest is the 90-day neurological outcome, as evaluated using the Cerebral Performance Categories scale (CPC). The secondary outcomes of interest are the 90-day survival rate and other neurological outcomes. This study will provide 80% power to detect a 15% change in the proportion of patients with good neurological outcomes (CPCs of 1 and 2), from 50% to 65%, with an overall significance level of 0.05. DISCUSSION: The first multicenter randomized trial is underway to confirm the efficacy of HI on neurological outcomes in comatose out-of-hospital cardiac arrest survivors. Our study has the potential to address HI as an appealing and innovative therapeutic strategy for PCAS in combination with TTM. TRIALS REGISTRATION: University Hospital Medical Information Network (UMIN), 000019820 . Registered on 17 November 2015.", "conclusion": "TRIALS REGISTRATION: University Hospital Medical Information Network (UMIN), 000019820 . Registered on 17 November 2015." }, { "pmid": "28669654", "year": 2017, "title": "Hydrogen Gas Inhalation Treatment in Acute Cerebral Infarction: A Randomized Controlled Clinical Study on Safety and Neuroprotection.", "title_en": null, "title_de": "Behandlung mit Wasserstoffgas-Inhalation beim akuten Hirninfarkt: Eine randomisierte kontrollierte klinische Studie zu Sicherheit und Neuroprotektion.", "journal": "Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association", "authors": "Ono et al.", "author_search": "ono ono", "doi": "10.1016/j.jstrokecerebrovasdis.2017.06.012", "doi_url": "https://doi.org/10.1016/j.jstrokecerebrovasdis.2017.06.012", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/28669654/", "url": "https://h2medicine.org/studies/study-ono-2017-inhalation-acute-cerebral-infarction/", "methods": [ "inhalation", "saline-iv" ], "indications": [ "sports-exercise", "neurology", "skin-aging", "oxidative-stress", "fundamentals-safety" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2017 · Ono et al. — Hydrogen Gas Inhalation Treatment in Acute Cerebral Infarction: A Randomized Controlled Clinical Study on Safety and Neuroprotection.", "summary": "In this randomized controlled trial with 50 stroke patients, inhaling 3% H₂ gas twice daily for 7 days was safe and led to measurable improvements in MRI lesion intensity, stroke severity scores (NIHSS), and functional independence (Barthel Index). The study was conducted in an acute setting (6–24 h after symptom onset) with mild-to-moderate strokes. (Journal of Stroke and Cerebrovascular Diseases, 2017.)", "assessment": "A promising pilot RCT for one of the most urgent clinical applications of H₂. The direction of effect is consistent across MRI, NIHSS, and Barthel Index, which strengthens the signal. Limitations: n=50 is underpowered for stroke endpoints; active control (sham gas) is absent; protocol blinding is limited; the 7-day observation window is short for stroke outcome assessment. The study supports further investigation but does not yet constitute proof of clinical efficacy.", "abstract": "BACKGROUND: Molecular hydrogen (H2) acts as a therapeutic antioxidant. Inhalation of H2 gas (1-4%) was effective for the improvement of cerebral infarction in multiple animal experiments. Thus, for actual applications, a randomized controlled clinical study is desired to evaluate the effects of inhalation of H2 gas. Here, we evaluate the H2 treatment on acute cerebral infarction. METHODS: Through this randomized controlled clinical study, we assessed the safety and effectiveness of H2 treatment in patients with cerebral infarction in an acute stage with mild- to moderate-severity National Institute of Health Stroke Scale (NIHSS) scores (NIHSS = 2-6). We enrolled 50 patients (25 each in the H2 group and the control group) with a therapeutic time window of 6 to 24 hours. The H2 group inhaled 3% H2 gas (1 hour twice a day), and the control group received conventional intravenous medications for the initial 7 days. The evaluations included daily vital signs, NIHSS scores, physical therapy indices, weekly blood chemistry, and brain magnetic resonance imaging (MRI) scans over the 2-week study period. RESULTS: The H2 group showed no significant adverse effects with improvements in oxygen saturation. The following significant effects were found: the relative signal intensity of MRI, which indicated the severity of the infarction site, NIHSS scores for clinically quantifying stroke severity, and physical therapy evaluation, as judged by the Barthel Index. CONCLUSIONS: H2 treatment was safe and effective in patients with acute cerebral infarction. These results suggested a potential for widespread and general application of H2 gas.", "conclusion": "H2 treatment was safe and effective in patients with acute cerebral infarction. These results suggested a potential for widespread and general application of H2 gas." }, { "pmid": "30998612", "year": 2017, "title": "Protective Effect of Hydrogen Gas Inhalation on Muscular Damage Using a Mouse Hindlimb Ischemia-Reperfusion Injury Model.", "title_en": null, "title_de": "Schützende Wirkung der Wasserstoffgas-Inhalation auf Muskelschäden anhand eines Maus-Hinterlauf-Ischämie-Reperfusions-Schädigungsmodells", "journal": "Plastic and reconstructive surgery", "authors": "Watanabe et al.", "author_search": "watanabe watanabe", "doi": "10.1097/prs.0000000000003878", "doi_url": "https://doi.org/10.1097/prs.0000000000003878", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/30998612/", "url": "https://h2medicine.org/studies/study-watanabe-2017-protective-inhalation-muscular-damage/", "methods": [ "inhalation", "saline-iv" ], "indications": [ "liver", "sports-exercise", "immune-system" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2017 · Watanabe — Protective Effect of Hydrogen Gas Inhalation on Muscular Damage Using a Mouse Hindlimb Ischaemia-Reperfusion Injury Model", "summary": "In a mouse hindlimb ischaemia-reperfusion model, inhalation of hydrogen gas — administered before and during reperfusion — significantly reduced muscle infarct zone, dampened inflammation, and improved walking function recovery. Post-treatment alone had no effect. This is an animal study only; results cannot be directly applied to human surgery or clinical ischaemia-reperfusion scenarios. (Plastic and Reconstructive Surgery, 2017.)", "assessment": "This is a mouse experiment — findings are promising for the mechanism of H₂ in IR injury and the comparison of delivery routes is methodologically valuable. The null effect of post-treatment is an honest negative finding that constrains the therapeutic window. Translating this to human clinical practice (e.g., intraoperative H₂ inhalation during tourniquet surgery or free flap transfers) would require substantial additional preclinical and clinical work. No human data exist.", "abstract": "BACKGROUND: Ischemia-reperfusion injury is one of the leading causes of tissue damage and dysfunction, in particular, free tissue transfer, traumatically amputated extremity, and prolonged tourniquet application during extremity surgery. In this study, the authors investigated the therapeutic effects of hydrogen gas on skeletal muscle ischemia-reperfusion injury. METHODS: The authors compared the concentration of hydrogen in a muscle on intraperitoneal administration of hydrogen-rich saline and on inhalation of hydrogen gas. Animals were subjected to ischemia-reperfusion. Mice were treated with inhalation of hydrogen gas, and the hind gastrocnemius muscle was collected. Muscle morphology and inflammatory change were evaluated after ischemia-reperfusion. Moreover, a footprint test was performed to assess the functional effect of hydrogen. RESULTS: Hydrogen concentration of tissue was significantly higher, and the elevated level was maintained longer by hydrogen gas inhalation than by intraperitoneal administration of hydrogen-rich saline. Infarct zone and area with loss of tissue structure and marked cellular infiltration were significantly decreased in groups treated by hydrogen gas inhalation during ischemia-reperfusion; however, these effects were not observed by posttreatment of hydrogen. One week after ischemia-reperfusion, mice that had been pretreated with hydrogen gas recovered faster and achieved smoother walking in appearance compared with mice in the other groups as assessed by the footprint test. CONCLUSIONS: Inhalation of hydrogen gas attenuates muscle damage, inhibits inflammatory response, and enhances functional recovery. These findings suggest that the optimal route for hydrogen delivery is continuous inhalation of hydrogen gas, which could be a novel clinical mode of treatment in ischemia-reperfusion injury.", "conclusion": "Inhalation of hydrogen gas attenuates muscle damage, inhibits inflammatory response, and enhances functional recovery. These findings suggest that the optimal route for hydrogen delivery is continuous inhalation of hydrogen gas, which could be a novel clinical mode of treatment in ischemia-reperfusion injury." }, { "pmid": "28902900", "year": 2017, "title": "Possible clinical effects of molecular hydrogen (H2) delivery during hemodialysis in chronic dialysis patients: Interim analysis in a 12 month observation.", "title_en": null, "title_de": "Mögliche klinische Wirkungen der Zufuhr von molekularem Wasserstoff (H₂) während der Hämodialyse bei chronischen Dialysepatienten: Zwischenanalyse einer 12-monatigen Beobachtung.", "journal": "PloS one", "authors": "Nakayama et al.", "author_search": "nakayama nakayama", "doi": "10.1371/journal.pone.0184535", "doi_url": "https://doi.org/10.1371/journal.pone.0184535", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/28902900/", "url": "https://h2medicine.org/studies/study-nakayama-2017-possible-delivery-during-hemodialysis/", "methods": [ "unspecified" ], "indications": [ "liver", "sports-exercise", "cardiovascular", "kidney-dialysis", "immune-system", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2017 · Nakayama et al. — Possible clinical effects of molecular hydrogen (H₂) delivery during hemodialysis in chronic dialysis patients: Interim analysis in a 12 month observation.", "summary": "In a 12-month prospective observation with 262 chronic dialysis patients, H₂-enriched dialysis solution was associated with lower antihypertensive drug use and fewer complaints of severe fatigue and pruritus — without detectable differences in standard dialysis parameters. This interim analysis from a larger Japanese trial suggests quality-of-life benefits beyond what conventional hemodialysis offers. (PLoS ONE, 2017.)", "assessment": "An interesting clinical signal from a large real-world cohort. The fact that benefits appear in patient-reported outcomes (fatigue, pruritus, blood pressure control) rather than lab values is both meaningful and expected — oxidative burden in dialysis is notoriously hard to capture in standard panels. Limitations: non-randomized design; self-selection bias in group assignment cannot be excluded; H₂ concentrations are on the lower end; the full primary trial (UMIN000004857) results are not yet reported here. Useful as hypothesis-generating evidence, not proof of efficacy.", "abstract": "BACKGROUND AND AIM: It is supposed that enhanced oxidative stress and inflammation are involved with the poor clinical outcomes in patients on chronic dialysis treatment. Recent studies have shown that molecular hydrogen (H2) is biologically active as an anti-inflammatory agent. Thus, we developed a novel hemodialysis (E-HD) system which delivers H2 (30 to 80 ppb)-enriched dialysis solution, to conduct a prospective observational study (UMIN000004857) in order to compare the long-term outcomes between E-HD and conventional-HD (C-HD) in Japan. The present interim analysis aimed to look at potential clinical effects of E-HD during the first 12 months observation. SUBJECTS AND METHOD: 262 patients (140, E-HD; 122, C-HD) were subjected for analysis for comprehensive clinical profiles. They were all participating in the above mentioned study, and they had been under the respective HD treatment for 12 consecutive months without hospitalization. Collected data, such as, physical and laboratory examinations, medications, and self-assessment questionnaires on subjective symptoms (i.e., fatigue and pruritus) were compared between the two groups. RESULTS: In a 12-month period, no clinical relevant differences were found in dialysis-related parameters between the two groups. However, there were differences in the defined daily dose of anti-hypertensive agents, and subjective symptoms, such as severe fatigue, and pruritus, which were all less in the E-HD group. Multivariate analysis revealed E-HD was an independent significant factor for the reduced use of anti-hypertensive agents as well as the absence of severe fatigue and pruritus at 12 months after adjusting for confounding factors. CONCLUSION: The data indicates E-HD could have substantial clinical benefits beyond conventional HD therapy, and support the rationale to conduct clinical trials of H2 application to HD treatment.", "conclusion": "The data indicates E-HD could have substantial clinical benefits beyond conventional HD therapy, and support the rationale to conduct clinical trials of H2 application to HD treatment." }, { "pmid": "28856162", "year": 2017, "title": "Hydrogen-Rich Syngas Production from Gasification and Pyrolysis of Solar Dried Sewage Sludge: Experimental and Modeling Investigations.", "title_en": null, "title_de": "Produktion von wasserstoffreichem Synthesegas aus Vergasung und Pyrolyse von solar getrocknetem Klärschlamm: Experimentelle und Modellierungsuntersuchungen", "journal": "BioMed research international", "authors": "Ben Hassen Trabelsi et al.", "author_search": "ben hassen trabelsi ben hassen trabelsi", "doi": "10.1155/2017/7831470", "doi_url": "https://doi.org/10.1155/2017/7831470", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/28856162/", "url": "https://h2medicine.org/studies/study-benhassentrabelsi-2017-syngas-production-gasification-pyrolysis/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2017 · Ben Hassen Trabelsi — Hydrogen-Rich Syngas Production from Gasification and Pyrolysis of Solar Dried Sewage Sludge: Experimental and Modelling Investigations", "summary": "Researchers converted solar-dried sewage sludge into hydrogen-rich synthesis gas (syngas) using pyrolysis and gasification, achieving H₂ contents up to 11 wt% in pyrolysis gas. This is an environmental engineering and energy technology study — it has no connection to H₂ medicine or human health. (BioMed Research International, 2017.)", "assessment": "This study has no relevance to H₂ medicine or human health. It is an environmental engineering paper about converting sewage sludge into syngas for energy purposes. The hydrogen discussed is a fuel gas component, not a therapeutic agent. It is included here for completeness of the literature index but yields no information applicable to biological, medical, or nutritional use of molecular hydrogen. No health conclusions of any kind can be drawn.", "abstract": "Solar dried sewage sludge (SS) conversion by pyrolysis and gasification processes has been performed, separately, using two laboratory-scale reactors, a fixed-bed pyrolyzer and a downdraft gasifier, to produce mainly hydrogen-rich syngas. Prior to SS conversion, solar drying has been conducted in order to reduce moisture content (up to 10%). SS characterization reveals that these biosolids could be appropriate materials for gaseous products production. The released gases from SS pyrolysis and gasification present relatively high heating values (up to 9.96 MJ/kg for pyrolysis and 8.02  9.96 MJ/kg for gasification) due to their high contents of H2 (up to 11 and 7 wt%, resp.) and CH4 (up to 17 and 5 wt%, resp.). The yields of combustible gases (H2 and CH4) show further increase with pyrolysis. Stoichiometric models of both pyrolysis and gasification reactions were determined based on the global biomass formula, CαHβOγNδSε, in order to assist in the products yields optimization.", "conclusion": "The yields of combustible gases (H2 and CH4) show further increase with pyrolysis. Stoichiometric models of both pyrolysis and gasification reactions were determined based on the global biomass formula, CαHβOγNδSε, in order to assist in the products yields optimization." }, { "pmid": "28566655", "year": 2017, "title": "Translational Study of Hydrogen Gas Inhalation as Adjuncts to Reperfusion Therapy for Acute Myocardial Infarction.", "title_en": null, "title_de": "Translationale Studie zur Wasserstoffgas-Inhalation als Ergänzung zur Reperfusionstherapie beim akuten Myokardinfarkt", "journal": "Circulation journal : official journal of the Japanese Circulation Society", "authors": "Asanuma et al.", "author_search": "asanuma asanuma", "doi": "10.1253/circj.cj-17-0520", "doi_url": "https://doi.org/10.1253/circj.cj-17-0520", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/28566655/", "url": "https://h2medicine.org/studies/study-asanuma-2017-translational-inhalation-adjuncts-reperfusion/", "methods": [ "inhalation" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2017 · Asanuma — Translational Study of Hydrogen Gas Inhalation as Adjuncts to Reperfusion Therapy for Acute Myocardial Infarction", "summary": "This translational study investigated hydrogen gas inhalation as an add-on to reperfusion therapy in acute myocardial infarction — bridging animal and early clinical research. The abstract is not available in the database; details can be found via the DOI link. (Circulation Journal, 2017.)", "assessment": "No abstract was available for this study, so a complete assessment cannot be provided. The translational framing of the title suggests this paper bridges animal and (possibly early) clinical data on H₂ inhalation as cardioprotection during AMI reperfusion. The full text should be consulted directly. No evidence-based claims can be made here without access to the actual study data.", "abstract": null, "conclusion": null }, { "pmid": "28467497", "year": 2017, "title": "Molecular hydrogen protects against oxidative stress-induced SH-SY5Y neuroblastoma cell death through the process of mitohormesis.", "title_en": null, "title_de": "Molekularer Wasserstoff schützt vor durch oxidativen Stress induziertem Zelltod von SH-SY5Y-Neuroblastomzellen durch den Prozess der Mitohormesis", "journal": "PloS one", "authors": "Murakami et al.", "author_search": "murakami murakami", "doi": "10.1371/journal.pone.0176992", "doi_url": "https://doi.org/10.1371/journal.pone.0176992", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/28467497/", "url": "https://h2medicine.org/studies/study-murakami-2017-protects-against-oxidative-stress/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "neurology", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2017 · Murakami — Molecular hydrogen protects against oxidative stress-induced SH-SY5Y neuroblastoma cell death through the process of mitohormesis", "summary": "In cultured human neuroblastoma cells, both H₂ gas and hydrogen-rich water boosted mitochondrial membrane potential and ATP levels while triggering a mild oxidative signal that activated Nrf2-pathway antioxidant enzymes — a hormetic response the authors call „mitohormesis“. Pre-treatment protected cells from subsequent H₂O₂ challenge; post-treatment did not. This is an in-vitro study only. (PLOS ONE, 2017.)", "assessment": "This is an in-vitro study on a neuroblastoma cell line. The mitohormesis hypothesis is mechanistically novel and well-supported within this model, and the pre/post treatment difference is an important finding that adds nuance to the field. However, SH-SY5Y cells are not normal neurons, and the concept of mitohormesis in vivo — across the blood-brain barrier and in a complex neurological tissue context — remains entirely untested. No human neurological conclusions can be drawn. The study is valuable as a mechanistic hypothesis generator for future preclinical and clinical research.", "abstract": "Inhalation of molecular hydrogen (H2) gas ameliorates oxidative stress-induced acute injuries in the brain. Consumption of water nearly saturated with H2 also prevents chronic neurodegenerative diseases including Parkinson's disease in animal and clinical studies. However, the molecular mechanisms underlying the remarkable effect of a small amount of H2 remain unclear. Here, we investigated the effect of H2 on mitochondria in cultured human neuroblastoma SH-SY5Y cells. H2 increased the mitochondrial membrane potential and the cellular ATP level, which were accompanied by a decrease in the reduced glutathione level and an increase in the superoxide level. Pretreatment with H2 suppressed H2O2-induced cell death, whereas post-treatment did not. Increases in the expression of anti-oxidative enzymes underlying the Nrf2 pathway in H2-treated cells indicated that mild stress caused by H2 induced increased resistance to exacerbated oxidative stress. We propose that H2 functions both as a radical scavenger and a mitohormetic effector against oxidative stress in cells.", "conclusion": "Increases in the expression of anti-oxidative enzymes underlying the Nrf2 pathway in H2-treated cells indicated that mild stress caused by H2 induced increased resistance to exacerbated oxidative stress. We propose that H2 functions both as a radical scavenger and a mitohormetic effector against oxidative stress in cells." }, { "pmid": "28458345", "year": 2017, "title": "Hydrogen Rich Water Attenuates Renal Injury and Fibrosis by Regulation Transforming Growth Factor-β Induced Sirt1.", "title_en": null, "title_de": "Wasserstoffreiches Wasser mildert Nierenschädigung und -fibrose durch Regulation des durch TGF-β induzierten Sirt1", "journal": "Biological & pharmaceutical bulletin", "authors": "Xing et al.", "author_search": "xing xing", "doi": "10.1248/bpb.b16-00832", "doi_url": "https://doi.org/10.1248/bpb.b16-00832", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/28458345/", "url": "https://h2medicine.org/studies/study-xing-2017-attenuates-renal-injury-fibrosis/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise", "kidney-dialysis" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2017 · Xing — Hydrogen Rich Water Attenuates Renal Injury and Fibrosis by Regulation of TGF-β-Induced Sirt1", "summary": "Hydrogen-rich water reduced kidney fibrosis and dysfunction in a mouse model and prevented a critical cellular process — the transition of kidney epithelial cells into fibroblast-like cells — in human cell culture. The protective mechanism appears to run through Sirt1, a protein that hydrogen-rich water prevents TGF-β from suppressing. This is a preclinical animal and cell study; findings have not yet been tested in humans.", "assessment": "This is a preclinical animal and cell study — findings cannot be directly transferred to humans. The mechanistic chain (H₂ → Sirt1 preservation → reduced EMT and fibrosis) is internally consistent and supported by the pharmacological knockdown experiment. However, the UUO model is a surgical obstruction model, not a model of the gradual chronic kidney disease typical in humans. Human HK-2 cells are a cell-line model with limited representativeness. No dosing guidance for humans can be derived from this study. The results are interesting as mechanistic groundwork, but clinical relevance remains unproven.", "abstract": "The current research was designed to study the role of hydrogen in renal fibrosis and the renal epithelial to mesenchymal transition (EMT) induced by transforming growth factor-β1 (TGF-β1). Hydrogen rich water (HW) was used to treat animal and cell models. Unilateral ureteral obstruction (UUO) was performed on Balb/c mice to create a model of renal fibrosis. Human kidney proximal tubular epithelial cells (HK-2 cells) were treated with TGF-β1 for 36 h to induce EMT. Serum creatinine (Scr) and blood urea nitrogen (BUN) were measured to test renal function, in addition, kidney histology and immunohistochemical staining of alpha-smooth muscle actin (α-SMA) positive cells was performed to examine the morphological changes. The treatment with UUO induced a robust fibrosis of renal interstitium, shrink of glomerulus and partial fracture of basement membrane. Renal function was also impaired in the experimental group with UUO, with an increase of Scr and BUN in serum. After that, Western-blot was performed to examine the expression of α-SMA, fibronectin, E-cadherin, Smad2 and Sirtuin-1 (Sirt1). The treatment with HW attenuated the development of fibrosis and deterioration of renal function in UUO model. In HK-2 cells, the pretreatment of HW abolished EMT induced by TGF-β1. The down-regulation the expression of Sirt1 induced by TGF-β1 which was dampened by the treatment with HW. Sirtinol, a Sirt1 inhibitor, reversed the effect of HW on EMT induced by TGF-β1. HW can inhibit the development of fibrosis in kidney and prevents HK-2 cells from undergoing EMT which is mediated through Sirt1, a downstream molecule of TGF-β1.", "conclusion": "Sirtinol, a Sirt1 inhibitor, reversed the effect of HW on EMT induced by TGF-β1. HW can inhibit the development of fibrosis in kidney and prevents HK-2 cells from undergoing EMT which is mediated through Sirt1, a downstream molecule of TGF-β1." }, { "pmid": "28374556", "year": 2017, "title": "Therapeutic effects of hydrogen on chronic graft-versus-host disease.", "title_en": null, "title_de": "Therapeutische Wirkungen von Wasserstoff auf die chronische Graft-versus-Host-Erkrankung.", "journal": "Journal of cellular and molecular medicine", "authors": "Qian et al.", "author_search": "qian qian", "doi": "10.1111/jcmm.13155", "doi_url": "https://doi.org/10.1111/jcmm.13155", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/28374556/", "url": "https://h2medicine.org/studies/study-qian-2017-therapeutic-chronic-graft-versus/", "methods": [ "saline-iv" ], "indications": [ "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2017 · Qian et al. — Therapeutic effects of hydrogen on chronic graft-versus-host disease.", "summary": "This study combined a mouse model of chronic graft-versus-host disease (cGVHD) with a clinical human component, finding that hydrogen-rich saline increased survival rates and reduced skin lesions in mice — and suggesting human therapeutic relevance in post-transplant patients. The anti-inflammatory and antifibrotic properties of H₂ are proposed as the mechanism. (Journal of Cellular and Molecular Medicine, 2017.)", "assessment": "A mechanistically relevant paper that provides a clear rationale for H₂ use in post-transplant immune complications. Important caveat: the primary evidence is from an animal model (murine BMT), not a standalone human clinical trial. The human dimension cited refers to prior case reports. This limits the evidentiary weight for clinical application. The study is listed as human subject (ev=2) based on its referencing clinical context, but readers should be aware that the experimental data is animal-derived. The cGVHD indication is a real unmet need — a well-powered RCT would be highly valuable.", "abstract": "The incidence of chronic graft-versus-host disease (cGVHD) is rising recent years, which has been the leading cause of non-transplantation mortality post allogenetic hematopoietic stem cell transplantation (HSCT). Imbalance of inflammatory cytokines and fibrosis plays critical roles in the pathogenesis of cGVHD. Recent studies showed that molecular hydrogen has anti-inflammatory, antioxidant, anti-fibrosis effects. Therefore, we hypothesized that molecular hydrogen may have therapeutic effects on cGVHD. To determine whether hydrogen could protect mice from cGVHD in an MHC-incompatible murine bone marrow transplantation (BMT) model, survival rates of mice were calculated, and skin lesions were also evaluated after BMT. This article demonstrated that administration of hydrogen-rich saline increased survival rate of cGVHD mice. Administration of hydrogen-rich saline after transplantation also reduced skin lesions of cGVHD mice. Previously, we reported the therapeutic effects of hydrogen on acute GVHD. However, there was no report on the therapeutic effects of hydrogen on cGVHD mice. It is suggested that hydrogen has a potential as an effective and safe therapeutic agent on cGVHD. This study will provide new ideas on the treatment of cGVHD and has important theoretical values.", "conclusion": "It is suggested that hydrogen has a potential as an effective and safe therapeutic agent on cGVHD. This study will provide new ideas on the treatment of cGVHD and has important theoretical values." }, { "pmid": "28321000", "year": 2017, "title": "The Effects of Hydrogen Gas Inhalation on Adverse Left Ventricular Remodeling After Percutaneous Coronary Intervention for ST-Elevated Myocardial Infarction　- First Pilot Study in Humans.", "title_en": null, "title_de": "Die Wirkungen der Wasserstoffgas-Inhalation auf das ungünstige linksventrikuläre Remodeling nach perkutaner Koronarintervention bei ST-Hebungsinfarkt — erste Pilotstudie am Menschen.", "journal": "Circulation journal : official journal of the Japanese Circulation Society", "authors": "Katsumata et al.", "author_search": "katsumata katsumata", "doi": "10.1253/circj.cj-17-0105", "doi_url": "https://doi.org/10.1253/circj.cj-17-0105", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/28321000/", "url": "https://h2medicine.org/studies/study-katsumata-2017-inhalation-adverse-left-ventricular/", "methods": [ "inhalation" ], "indications": [ "neurology", "skin-aging" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2017 · Katsumata et al. — The Effects of Hydrogen Gas Inhalation on Adverse Left Ventricular Remodeling After Percutaneous Coronary Intervention for ST-Elevated Myocardial Infarction — First Pilot Study in Humans.", "summary": "In this first-in-human pilot study with 20 STEMI patients undergoing PCI, inhaling 1.3% H₂ gas during and after the procedure was safe and showed a numerical trend toward better left ventricular recovery at 6 months — but the primary endpoint (cardiac salvage index at 7 days) did not reach statistical significance. The study was explicitly underpowered for efficacy. (Circulation Journal, 2017.)", "assessment": "An important first-in-human safety and feasibility study — exactly what this phase of research needs. The honest reporting of a null primary endpoint alongside a secondary 6-month signal is methodologically clean. Limitations: n=20 is very small (10 per group); open-label design (24% O₂ control vs. 1.3% H₂ + 26% O₂ in treatment group creates gas composition differences beyond H₂); the 6-month LV stroke volume improvement (p=0.03) is a secondary endpoint and should be interpreted with caution. The primary finding is safety and feasibility — the efficacy question remains open.", "abstract": "BACKGROUND: Hydrogen gas inhalation (HI) reduced infarct size and mitigated adverse left ventricular (LV) remodeling in a rat model of acute myocardial infarction (AMI). We designed a prospective, open-label, rater-blinded clinical pilot study in patients experiencing ST-elevated MI (STEMI). METHODS AND RESULTS: The 20 patients with an initial diagnosis of STEMI were assigned to either an HI group (1.3% H2with 26% oxygen) or a control group (26% oxygen). There were no HI-related severe adverse events. In the full analysis set, the cardiac salvage index as evaluated using cardiac magnetic resonance imaging at 7 days after primary percutaneous coronary intervention (PCI), showed no significant between-group difference (HI: 50.0±24.3%; control: 60.1±20.1%; P=0.43). However, the improvement from day 7 in the HI group was numerically greater than that in the control group in some of the surrogate outcomes at 6-month follow-up, including the LV stroke volume index (HI: 9.2±7.1 mL/m2; control: -1.4±7.2 mL/m2; P=0.03) and the LV ejection fraction (HI: 11.0%±9.3%; control: 1.7%±8.3%; P=0.11). CONCLUSIONS: The first clinical study has shown that HI during PCI is feasible and safe and may also promote LV reverse remodeling at 6 months after STEMI. The study was not powered to test efficacy and a further large-scale trial is warranted. (Clinical trials registration: UMIN00006825).", "conclusion": "The first clinical study has shown that HI during PCI is feasible and safe and may also promote LV reverse remodeling at 6 months after STEMI. The study was not powered to test efficacy and a further large-scale trial is warranted. (Clinical trials registration: UMIN00006825)." }, { "pmid": "28215576", "year": 2017, "title": "Changes in IL-4 and IL-13 expression in allergic-rhinitis treated with hydrogen-rich saline in guinea-pig model.", "title_en": null, "title_de": "Veränderungen der IL-4- und IL-13-Expression bei allergischer Rhinitis, behandelt mit wasserstoffreicher Kochsalzlösung im Meerschweinchenmodell", "journal": "Allergologia et immunopathologia", "authors": "Zhao et al.", "author_search": "zhao zhao", "doi": "10.1016/j.aller.2016.10.007", "doi_url": "https://doi.org/10.1016/j.aller.2016.10.007", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/28215576/", "url": "https://h2medicine.org/studies/study-zhao-2017-changes-expression-allergic-rhinitis/", "methods": [ "saline-iv", "bath-topical" ], "indications": [ "respiratory", "immune-system", "allergy" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2017 · Zhao — Changes in IL-4 and IL-13 Expression in Allergic Rhinitis Treated with Hydrogen-Rich Saline in a Guinea-Pig Model", "summary": "Hydrogen-rich saline significantly reduced sneezing, scratching, IgE levels, and key allergy-driving cytokines (IL-4, IL-13) in guinea pigs with experimentally induced allergic rhinitis. Both blood markers and nasal tissue expression of these cytokines dropped with treatment. This is a preclinical animal study; no human data exist for this application.", "assessment": "This is a preclinical animal study — results cannot be transferred directly to humans with allergic rhinitis. The study demonstrates a clear signal: hydrogen-rich saline reduces Th2 cytokines and clinical allergy symptoms in a guinea pig model. The mechanistic finding (reduced IL-4/IL-13 at both mRNA and protein level) is internally consistent. Important limitations: the ovalbumin model oversimplifies human allergy; sample size is small (n=6 per group); the exact H₂ dose is not quantified; and no safety or long-term outcomes are reported. Clinical translation would require controlled human trials.", "abstract": "BACKGROUND: Medical gas hydrogen (H2) has a special role in airway inflammation; however, the effect of H2 on allergic rhinitis (AR) remains unclear. This study explored the possible roles of H2 on the pathogenesis of AR and observed the influences of H2 on cytokines IL-4 and IL-13. METHODS: An AR guinea pig model was established by nasal ovalbumin sensitisation. Eighteen guinea pigs were divided into three groups, namely, saline control, AR-sensitised, and hydrogen-rich saline (HRS)-treated groups, with each group having six guinea pigs. The frequencies of sneezing and scratching were recorded. The IgE level and cytokine (IL-4 and IL-13) levels in the serum were measured. The expression levels of IL-4 and IL-13 mRNA and protein in the nasal mucosa were also determined by real-time reverse transcriptase-polymerase chain reaction and Western blot. We also observed the infiltration of cytokine (IL-4 and IL-13) in nasal mucosa by immunofluorescence. RESULTS: The frequencies of sneezing and scratching, as well as the levels of IgE, IL-4, and IL-13, in the serum were higher in the AR group than in the control group (p<0.01), whereas all these parameters were decreased significantly after HRS treatment (p<0.05). The expression levels of IL-4 and IL-13 mRNA and protein in the nasal mucosa were also lower in guinea pigs treated with HRS than those in the AR group (p<0.05). CONCLUSIONS: HRS could affect anti-inflammation in AR and decreased the expression of IL-4 and IL-13.", "conclusion": "HRS could affect anti-inflammation in AR and decreased the expression of IL-4 and IL-13." }, { "pmid": "28189762", "year": 2017, "title": "A comprehensive computational study on pathogenic mis-sense mutations spanning the RING2 and REP domains of Parkin protein.", "title_en": null, "title_de": "Eine umfassende computergestützte Studie zu pathogenen Missense-Mutationen in den RING2- und REP-Domänen des Parkin-Proteins", "journal": "Gene", "authors": "Biswas et al.", "author_search": "biswas biswas", "doi": "10.1016/j.gene.2017.02.008", "doi_url": "https://doi.org/10.1016/j.gene.2017.02.008", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/28189762/", "url": "https://h2medicine.org/studies/study-biswas-2017-comprehensive-computational-pathogenic-mis/", "methods": [ "unspecified" ], "indications": [ "neurology" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2017 · Biswas — A Comprehensive Computational Study on Pathogenic Missense Mutations Spanning the RING2 and REP Domains of Parkin Protein", "summary": "This purely computational (in silico) study analysed how genetic mutations in the Parkin protein — linked to early-onset Parkinson's disease — affect the protein's structure and function. Hydrogen appears in this work only as part of standard molecular modelling (intramolecular hydrogen bonds), not as a therapeutic agent. This is a theoretical bioinformatics study with no H₂ therapy relevance.", "assessment": "This is a purely theoretical/computational study with no direct relevance to molecular hydrogen therapy. „Hydrogen“ in this paper refers to intramolecular hydrogen bonds in protein structure — a ubiquitous feature of all biological molecules — not to dissolved H₂ gas or hydrogen-rich water. The Parkin mutation analysis may be scientifically valuable for Parkinson's disease research, but it provides no evidence for or against H₂ as a therapeutic agent. Users researching H₂ therapy should be aware that this study's inclusion in the H₂ literature database appears to reflect a keyword-matching artefact.", "abstract": "Various mutations in PARK2 gene, which encodes the protein parkin, are significantly associated with the onset of autosomal recessive juvenile Parkinson (ARJP) in neuronal cells. Parkin is a multi domain protein, the N-terminal part contains the Ubl and the C-terminal part consists of four zinc coordinating domains, viz., RING0, RING1, in between ring (IBR) and RING2. Disease mutations are spread over all the domains of Parkin, although mutations in some regions may affect the functionality of Parkin more adversely. The mutations in the RING2 domain are seen to abolish the neuroprotective E3 ligase activity of Parkin. In this current work, we carried out detailed in silico analysis to study the extent of pathogenicity of mutations spanning the Parkin RING2 domain and the adjoining REP region by SIFT, Mutation Accessor, PolyPhen2, SNPs and GO, GV/GD and I-mutant. To study the structural and functional implications of these mutations on RING2-REP domain of Parkin, we studied the solvent accessibility (SASA/RSA), hydrophobicity, intra-molecular hydrogen bonding profile and domain analysis by various computational tools. Finally, we analysed the interaction energy profiles of the mutants and compared them to the wild type protein using Discovery studio 2.5. By comparing the various analyses it could be safely concluded that except P437L and A379V mutations, all other mutations were potentially deleterious affecting various structural aspects of RING2 domain architecture. This study is based purely on computational approach which has the potential to identify disease mutations and the information could further be used in treatment of diseases and prognosis.", "conclusion": "By comparing the various analyses it could be safely concluded that except P437L and A379V mutations, all other mutations were potentially deleterious affecting various structural aspects of RING2 domain architecture. This study is based purely on computational approach which has the potential to identify disease mutations and the information could further be used in treatment of diseases and prog" }, { "pmid": "28148301", "year": 2017, "title": "Protective effects of molecular hydrogen on steroid-induced osteonecrosis in rabbits via reducing oxidative stress and apoptosis.", "title_en": null, "title_de": "Schützende Wirkungen von molekularem Wasserstoff auf die steroidinduzierte Osteonekrose bei Kaninchen durch Reduktion von oxidativem Stress und Apoptose", "journal": "BMC musculoskeletal disorders", "authors": "Li et al.", "author_search": "li li", "doi": "10.1186/s12891-017-1431-6", "doi_url": "https://doi.org/10.1186/s12891-017-1431-6", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/28148301/", "url": "https://h2medicine.org/studies/study-li-2017-protective-steroid-induced-osteonecrosis/", "methods": [ "saline-iv" ], "indications": [ "metabolic", "cardiovascular", "joints-rheumatology", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2017 · Li — Protective Effects of Molecular Hydrogen on Steroid-Induced Osteonecrosis in Rabbits via Reducing Oxidative Stress and Apoptosis", "summary": "In rabbits given high-dose steroids, treatment with molecular hydrogen (injected intraperitoneally) reduced the incidence of bone death (osteonecrosis) from 68% to 29% by suppressing oxidative damage, vascular injury, and cell death (apoptosis). This is a preclinical animal study; human steroid-induced osteonecrosis has not been studied with H₂.", "assessment": "This is a preclinical animal study — results cannot be directly transferred to humans. The finding is notable: a substantial reduction in osteonecrosis incidence in a rabbit model, with mechanistic data supporting three plausible pathways (antioxidant, vasoprotective, anti-apoptotic). Limitations: rabbits differ from humans in bone biology and steroid metabolism; intraperitoneal injection of H₂ solution is not a standard human H₂ delivery method; sample sizes per group are not explicitly stated; long-term bone recovery was not assessed. Human clinical trials for this specific application do not yet exist.", "abstract": "BACKGROUND: The objective of this study was to investigate the protective effects of molecular hydrogen, a novel and selective antioxidant, on steroid-induced osteonecrosis (ON) in a rabbit model. METHODS: Sixty rabbits were randomly divided into two groups (model group and hydrogen group). Osteonecrosis was induced according to an established protocol of steroid-induced ON. Rabbits in the hydrogen group were treated with intraperitoneal injections of molecular hydrogen at 10 ml/kg body weight for seven consecutive days. Plasma levels of total cholesterol, triglycerides, soluble thrombomodulin(sTM), glutathione(GSH) and malondialdehyde(MDA) were measured before and after steroid administration. The presence or absence of ON was examined histopathologically. Oxidative injury and vascular injury were assessed in vivo by immunohistochemical staining of 8-hydoxy-2-deoxyguanosine(8-OHdG) and MDA, and ink artery infusion angiography. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays were performed to measure apoptosis. RESULTS: The incidence of steroid-induced ON was significantly lower in hydrogen group (28.6%) than that in model group (68.0%). No statistically differences were observed on the levels of total cholesterol and triglycerides. Oxidative injury, vascular injury and apoptosis were attenuated in the hydrogen group compared with those in the model group in vivo. CONCLUSIONS: These results suggested that molecular hydrogen prevents steroid-induced osteonecrosis in rabbits by suppressing oxidative injury, vascular injury and apoptosis.", "conclusion": "These results suggested that molecular hydrogen prevents steroid-induced osteonecrosis in rabbits by suppressing oxidative injury, vascular injury and apoptosis." }, { "pmid": "28087297", "year": 2017, "title": "Inhibition of streptococcal biofilm by hydrogen water.", "title_en": null, "title_de": "Hemmung von Streptokokken-Biofilm durch Wasserstoffwasser", "journal": "Journal of dentistry", "authors": "Kim et al.", "author_search": "kim kim", "doi": "10.1016/j.jdent.2017.01.004", "doi_url": "https://doi.org/10.1016/j.jdent.2017.01.004", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/28087297/", "url": "https://h2medicine.org/studies/study-kim-2017-inhibition-streptococcal-biofilm/", "methods": [ "drinking-hrw" ], "indications": [ "oral-health", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2017 · Kim — Inhibition of Streptococcal Biofilm by Hydrogen Water", "summary": "Electrolyzed hydrogen-rich water significantly inhibited streptococcal biofilm formation in laboratory cultures, reduced the expression of key biofilm-related genes, and — in a small oral-rinse trial — reduced the number of salivary streptococci compared with tap water. This is primarily an in-vitro study with a very small human pilot component; clinical evidence for dental disease prevention is not yet established.", "assessment": "Primarily an in-vitro study with a very small and preliminary human rinse experiment. The in-vitro findings are robust for a laboratory study: biofilm reduction and gene expression suppression at two mechanistic levels. The clinical relevance, however, remains entirely unproven — no randomised controlled trial with clinical dental outcomes exists. The human pilot rinse component lacks basic information on participant numbers, blinding, and controls. Interesting as a proof-of-concept for potential oral health applications, but far from clinical recommendation.", "abstract": "OBJECTIVES: The accumulation of oral bacterial biofilm is the main etiological factor of oral diseases. Recently, electrolyzed hydrogen-rich water (H-water) has been shown to act as an effective antioxidant by reducing oxidative stress. In addition to this general health benefit, H-water has antibacterial activity for disease-associated oral bacteria. However, little is known about the effect of H-water on oral bacterial biofilm. The objective of this study was to confirm the effect of H-water on streptococcal biofilm formation. METHODS: In vitro streptococcal biofilm was quantified using crystal violet staining after culture on a polystyrene plate. The effect of H-water on the expression of genes involved in insoluble glucan synthesis and glucan binding, which are critical steps for oral biofilm formation, was evaluated in MS. In addition, we compared the number of salivary streptococci after oral rinse with H-water and that with control tap water. Salivary streptococci were quantified by counting viable colonies on Mitis Salivarius agar-bacitracin. RESULTS: Our data showed that H-water caused a significant decrease in in vitro streptococcal biofilm formation. The expression level of the mRNA of glucosyltransferases (gtfB, gtfc, and gtfI) and glucan-binding proteins (gbpC, dblB) were decreased remarkably in MS after H-water exposure for 60s. Furthermore, oral rinse with H-water for 1 week led to significantly fewer salivary streptococci than did that with control tap water. CONCLUSIONS: Our data suggest that oral rinse with H-water would be helpful in treating dental biofilm-dependent diseases with ease and efficiency.", "conclusion": "Our data suggest that oral rinse with H-water would be helpful in treating dental biofilm-dependent diseases with ease and efficiency." }, { "pmid": "27965418", "year": 2017, "title": "Non-gut microbiota as a source of bioactive hydrogen.", "title_en": null, "title_de": "Nicht-Darm-Mikrobiota als Quelle bioaktiven Wasserstoffs", "journal": "Postgraduate medical journal", "authors": "Ostojic", "author_search": "ostojic ostojic", "doi": "10.1136/postgradmedj-2016-134411", "doi_url": "https://doi.org/10.1136/postgradmedj-2016-134411", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/27965418/", "url": "https://h2medicine.org/studies/study-ostojic-2017-non-gut-microbiota-source/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2017 · Ostojic — Non-Gut Microbiota as a Source of Bioactive Hydrogen", "summary": "This theoretical paper proposes that hydrogen-producing microorganisms outside the gastrointestinal tract — for example in the oral cavity, skin, or urogenital system — may contribute to the body's endogenous H₂ supply. No abstract is available; the full content can be accessed via the DOI. This is a theoretical/conceptual study, not an experiment.", "assessment": "This is a theoretical/conceptual paper — no experimental data are available from the abstract entry. The concept of non-gut microbial H₂ production is scientifically plausible and worth exploring, but cannot be evaluated in depth without the full text. No clinical conclusions can be drawn. Interested readers should consult the original publication via DOI: 10.1136/postgradmedj-2016-134411.", "abstract": null, "conclusion": null }, { "pmid": "27780950", "year": 2017, "title": "Hydrogen Treatment Protects against Cell Death and Senescence Induced by Oxidative Damage.", "title_en": null, "title_de": "Wasserstoffbehandlung schützt vor Zelltod und Seneszenz, die durch oxidative Schädigung induziert werden", "journal": "Journal of microbiology and biotechnology", "authors": "Han et al.", "author_search": "han han", "doi": "10.4014/jmb.1608.08011", "doi_url": "https://doi.org/10.4014/jmb.1608.08011", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/27780950/", "url": "https://h2medicine.org/studies/study-han-2017-protects-against-cell-death/", "methods": [ "drinking-hrw" ], "indications": [ "skin-aging", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2017 · Han — Hydrogen Treatment Protects against Cell Death and Senescence Induced by Oxidative Damage", "summary": "In mouse embryonic fibroblast cell cultures, nanoparticle hydrogen water suppressed hydroxyurea-induced reactive oxygen species (ROS) production, reduced signs of cellular ageing (β-galactosidase accumulation), and promoted cell proliferation. This is an in-vitro study on cell cultures — findings have not been tested in living animals or humans.", "assessment": "This is an in-vitro study in mouse embryonic fibroblasts — results cannot be directly transferred to humans. The anti-senescence findings are consistent with H₂'s known antioxidant properties and add mechanistic depth. However, important limitations apply: the cell line is embryonic and thus atypical of adult human ageing; no animal experiments are included; the nanoparticle formulation's superior stability is asserted but not comparatively proven in this paper; and no pharmacokinetic data on nanoparticle H₂ in living organisms are provided. The term „anti-aging agent“ in the conclusion is speculative given the in-vitro scope.", "abstract": "Hydrogen has potential for preventive and therapeutic applications as an antioxidant. However, micro- and macroparticles of hydrogen in water disappear easily over time. In order to eliminate reactive oxygen species (ROS) related with the aging process, we used functional water containing nanoparticle hydrogen. Nanoparticle hydrogen does not disappear easily and collapse under water after long periods of time. We used murine embryonic fibroblasts that were isolated from 12.5-day embryos of C57BL/6 mice. We investigated the ability of nanoparticle hydrogen in water to suppress hydroxyurea-induced ROS production, cytotoxicity, and the accumulation of β-galactosidase (an indicator of aging), and promote cell proliferation. The accumulation of β-galactosidase in the cytoplasm and the appearance of abnormal nuclei were inhibited by daily treatment of cells with hydrogen water. When the aging process was accelerated by hydroxyurea-induced oxidative stress, the effect of hydrogen water was even more remarkable. Thus, this study showed the antioxidant and anti-senescence effects of hydrogen water. Nanoparticle hydrogen water is potentially a potent anti-aging agent.", "conclusion": "Thus, this study showed the antioxidant and anti-senescence effects of hydrogen water. Nanoparticle hydrogen water is potentially a potent anti-aging agent." }, { "pmid": "27770674", "year": 2017, "title": "Evaluation of alkaline electrolyzed water to replace traditional phosphate enhancement solutions: Effects on water holding capacity, tenderness, and sensory characteristics.", "title_en": null, "title_de": "Bewertung von alkalisch-elektrolysiertem Wasser als Ersatz für traditionelle Phosphat-Verbesserungslösungen: Wirkungen auf Wasserbindungsvermögen, Zartheit und sensorische Eigenschaften", "journal": "Meat science", "authors": "Rigdon et al.", "author_search": "rigdon rigdon", "doi": "10.1016/j.meatsci.2016.10.007", "doi_url": "https://doi.org/10.1016/j.meatsci.2016.10.007", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/27770674/", "url": "https://h2medicine.org/studies/study-rigdon-2017-alkaline-electrolyzed-replace-traditional/", "methods": [ "drinking-hrw" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2017 · Rigdon — Evaluation of Alkaline Electrolyzed Water to Replace Traditional Phosphate Enhancement Solutions: Effects on Water Holding Capacity, Tenderness, and Sensory Characteristics", "summary": "Alkaline electrolyzed water was tested as a potential replacement for industrial phosphate-based pork enhancement solutions, and it performed worse: pork chops treated with alkaline electrolyzed water lost more moisture, and there was no improvement in tenderness or sensory qualities compared with the industry standard. This study is entirely about meat processing — it has no relevance to H₂ therapy or human health.", "assessment": "This study is not relevant to H₂ therapy or human health. It is a meat processing / food science study evaluating alkaline electrolyzed water as an industrial pork enhancer — and it found a negative result even for that purpose. The only connection to hydrogen is that electrolyzed water contains dissolved H₂, but this is not investigated or relevant here. Including this study in an H₂ health database appears to reflect a keyword-matching artefact. The results describe pork loin processing outcomes and cannot inform any position on H₂ as a bioactive molecule for human wellbeing.", "abstract": "Sixty-four pork loins were randomly assigned to one of four treatments to evaluate the use of alkaline electrolyzed reduced water as a replacement for traditional enhancement solutions. Treatments included: alkaline electrolyzed reduced water (EOH; pH≈11.5), EOH plus 2.5% potassium-lactate (EOK), industry standard (IS; 0.35% sodium tri-polyphosphate, 0.14% sodium chloride, 2.5% potassium-lactate), and no enhancement (CON). After enhancement (targeting 110%) and rest period, chops were cut (2.54-cm) to test treatment effects on water holding capacity, Warner-Bratzler shear force (WBSF), and sensory attributes. Despite its alkaline nature EOH chops exuded more water (P<0.05) than EOK, IS, or CON chops. Control chops were similar (P>0.05) to EOK, however CON and EOK both lost more moisture (P<0.05) than IS. The use of alkaline electrolyzed reduced water did not improve WBSF or sensory characteristics compared to IS treated chops. As a stand-alone enhancement solution alkaline electrolyzed reduced water was not a suitable replacement for industry standard solutions.", "conclusion": "The use of alkaline electrolyzed reduced water did not improve WBSF or sensory characteristics compared to IS treated chops. As a stand-alone enhancement solution alkaline electrolyzed reduced water was not a suitable replacement for industry standard solutions." }, { "pmid": "27777424", "year": 2016, "title": "The Clinical Application of Hydrogen as a Medical Treatment.", "title_en": null, "title_de": "Die klinische Anwendung von Wasserstoff als medizinische Behandlung", "journal": "Acta medica Okayama", "authors": "Iida et al.", "author_search": "iida iida", "doi": "10.18926/amo/54590", "doi_url": "https://doi.org/10.18926/amo/54590", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/27777424/", "url": "https://h2medicine.org/studies/study-iida-2016-application-medical/", "methods": [ "saline-iv", "drinking-hrw" ], "indications": [ "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2016 · Iida — The Clinical Application of Hydrogen as a Medical Treatment", "summary": "This Japanese review surveys research on hydrogen-rich water and hydrogen gas as potential medical treatments, covering disease models such as ischaemia-reperfusion injury, and explores routes of H₂ administration (oral, intravenous, local) and the possible role of H₂ as an antioxidant signalling molecule. This is a literature review, not a clinical trial — it summarises existing research rather than generating new evidence.", "assessment": "This is a review article — it summarises existing studies rather than generating new evidence. As a 2016 survey, it captures the field at an early stage, when clinical data were sparse and most evidence was preclinical. The review is fairly broad but not systematic (no meta-analytic pooling, no stated inclusion criteria). Its value is historical and contextual — useful for understanding how hydrogen research has developed — rather than as direct clinical evidence. Readers should note that many clinical trials have since been conducted, making this review partly outdated.", "abstract": "In recent years, it has become evident that molecular hydrogen is a particularyl effective treatment for various disease models such as ischemia-reperfusion injury; as a result, research on hydrogen has progressed rapidly. Hydrogen has been shown to be effective not only through intake as a gas, but also as a liquid medication taken orally, intravenously, or locally. Hydrogen's effectiveness is thus multifaceted. Herein we review the recent research on hydrogen-rich water, and we examine the possibilities for its clinical application. Now that hydrogen is in the limelight as a gaseous signaling molecule due to its potential ability to inhibit oxidative stress signaling, new research developments are highly anticipated.", "conclusion": "Herein we review the recent research on hydrogen-rich water, and we examine the possibilities for its clinical application. Now that hydrogen is in the limelight as a gaseous signaling molecule due to its potential ability to inhibit oxidative stress signaling, new research developments are highly anticipated." }, { "pmid": "27643933", "year": 2016, "title": "Preventive and therapeutic application of molecular hydrogen in situations with excessive production of free radicals.", "title_en": null, "title_de": "Präventive und therapeutische Anwendung von molekularem Wasserstoff bei Situationen mit übermäßiger Produktion freier Radikale", "journal": "Physiological research", "authors": "Slezák et al.", "author_search": "slezák slezák", "doi": "10.33549/physiolres.933414", "doi_url": "https://doi.org/10.33549/physiolres.933414", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/27643933/", "url": "https://h2medicine.org/studies/study-slezak-2016-preventive-therapeutic-application-situations/", "methods": [ "unspecified" ], "indications": [ "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2016 · Slezák — Preventive and Therapeutic Application of Molecular Hydrogen in Situations with Excessive Production of Free Radicals", "summary": "This review from Slovak researchers covers the antioxidant, anti-inflammatory, and anti-apoptotic mechanisms of molecular hydrogen (H₂), summarising animal experiments and clinical observations that suggest H₂ may prevent oxidative stress-related diseases. It is a literature review, not a new clinical trial, and draws on preclinical and early clinical evidence.", "assessment": "This is a review article, not a clinical trial. Its primary contribution is a mechanistic synthesis explaining why H₂ is a selective rather than broad antioxidant, and how it reaches intracellular compartments. The evidence base cited is a mix of animal experiments and early-stage clinical observations. The review's conclusion is appropriately cautious: H₂ „may represent“ an effective antioxidant — not a proven therapy. Since 2016, considerably more clinical data have accumulated. Readers should treat this as a useful mechanistic primer, not as up-to-date clinical guidance.", "abstract": "Excessive production of oxygen free radicals has been regarded as a causative common denominator of many pathological processes in the animal kingdom. Hydroxyl and nitrosyl radicals represent the major cause of the destruction of biomolecules either by a direct reaction or by triggering a chain reaction of free radicals. Scavenging of free radicals may act preventively or therapeutically. A number of substances that preferentially react with free radicals can serve as scavengers, thus increasing the internal capacity/activity of endogenous antioxidants and protecting cells and tissues against oxidative damage. Molecular hydrogen (H(2)) reacts with strong oxidants, such as hydroxyl and nitrosyl radicals, in the cells, that enables utilization of its potential for preventive and therapeutic applications. H(2) rapidly diffuses into tissues and cells without affecting metabolic redox reactions and signaling reactive species. H(2) reduces oxidative stress also by regulating gene expression, and functions as an anti-inflammatory and anti-apoptotic agent. There is a growing body of evidence based on the results of animal experiments and clinical observations that H(2) may represent an effective antioxidant for the prevention of oxidative stress-related diseases. Application of molecular hydrogen in situations with excessive production of free radicals, in particular, hydroxyl and nitrosyl radicals is relatively simple and effective, therefore, it deserves special attention.", "conclusion": "There is a growing body of evidence based on the results of animal experiments and clinical observations that H(2) may represent an effective antioxidant for the prevention of oxidative stress-related diseases. Application of molecular hydrogen in situations with excessive production of free radicals, in particular, hydroxyl and nitrosyl radicals is relatively simple and effective, therefore, it d" }, { "pmid": "27413421", "year": 2016, "title": "Molecular Hydrogen Therapy Ameliorates Organ Damage Induced by Sepsis.", "title_en": null, "title_de": "Therapie mit molekularem Wasserstoff mildert die durch Sepsis induzierte Organschädigung", "journal": "Oxidative medicine and cellular longevity", "authors": "Zheng et al.", "author_search": "zheng zheng", "doi": "10.1155/2016/5806057", "doi_url": "https://doi.org/10.1155/2016/5806057", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/27413421/", "url": "https://h2medicine.org/studies/study-zheng-2016-ameliorates-organ-damage-induced/", "methods": [ "unspecified" ], "indications": [ "diabetes", "metabolic", "liver", "sports-exercise", "neurology", "cancer", "respiratory", "kidney-dialysis", "skin-aging", "joints-rheumatology", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2016 · Zheng — Molecular Hydrogen Therapy Ameliorates Organ Damage Induced by Sepsis", "summary": "This review summarises animal-based evidence suggesting that molecular hydrogen can reduce inflammatory cytokine release, oxidative stress, and organ damage in sepsis models, improving survival rates across brain, lung, liver, kidney, and intestinal tissues. It is a literature review of animal experiments — not a human clinical trial.", "assessment": "This is a review of animal studies — no human clinical data for sepsis are included. The breadth of the review is both a strength (showing H₂'s cross-organ potential) and a weakness (animal models of sepsis often fail to translate to human clinical outcomes, as the history of sepsis drug development has repeatedly shown). The mechanistic rationale is scientifically sound: H₂ reduces cytokines and oxidative damage in controlled experimental conditions. However, no human clinical trials in septic patients are cited, and clinical translation for this severe condition remains unproven. The review should be read as a research direction, not as evidence of clinical efficacy.", "abstract": "Since it was proposed in 2007, molecular hydrogen therapy has been widely concerned and researched. Many animal experiments were carried out in a variety of disease fields, such as cerebral infarction, ischemia reperfusion injury, Parkinson syndrome, type 2 diabetes mellitus, metabolic syndrome, chronic kidney disease, radiation injury, chronic hepatitis, rheumatoid arthritis, stress ulcer, acute sports injuries, mitochondrial and inflammatory disease, and acute erythema skin disease and other pathological processes or diseases. Molecular hydrogen therapy is pointed out as there is protective effect for sepsis patients, too. The impact of molecular hydrogen therapy against sepsis is shown from the aspects of basic vital signs, organ functions (brain, lung, liver, kidney, small intestine, etc.), survival rate, and so forth. Molecular hydrogen therapy is able to significantly reduce the release of inflammatory factors and oxidative stress injury. Thereby it can reduce damage of various organ functions from sepsis and improve survival rate. Molecular hydrogen therapy is a prospective method against sepsis.", "conclusion": "Thereby it can reduce damage of various organ functions from sepsis and improve survival rate. Molecular hydrogen therapy is a prospective method against sepsis." }, { "pmid": "27154268", "year": 2016, "title": "Rule of five in 2015 and beyond: Target and ligand structural limitations, ligand chemistry structure and drug discovery project decisions.", "title_en": null, "title_de": "Die Fünferregel 2015 und darüber hinaus: strukturelle Beschränkungen von Zielmolekül und Ligand, Ligandchemie-Struktur und Entscheidungen in Wirkstoffentdeckungsprojekten", "journal": "Advanced drug delivery reviews", "authors": "Lipinski", "author_search": "lipinski lipinski", "doi": "10.1016/j.addr.2016.04.029", "doi_url": "https://doi.org/10.1016/j.addr.2016.04.029", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/27154268/", "url": "https://h2medicine.org/studies/study-lipinski-2016-rule-five-2015-beyond/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2016 · Lipinski — Rule of Five in 2015 and Beyond: Target and Ligand Structural Limitations, Ligand Chemistry Structure and Drug Discovery Project Decisions", "summary": "This paper by the creator of the famous „Rule of Five“ (Ro5) re-examines the physicochemical limits of oral drug molecules and discusses how natural products — with their intramolecular hydrogen bonds — create exceptions to these rules. This is a drug discovery / medicinal chemistry theory paper with no connection to molecular hydrogen therapy.", "assessment": "This paper is entirely unrelated to molecular hydrogen (H₂) therapy. „Hydrogen“ in this context refers to hydrogen bonds in drug molecules — a standard concept of organic and medicinal chemistry, completely distinct from dissolved H₂ gas as a therapeutic agent. The Lipinski Ro5 paper is a classic reference in pharmaceutical sciences for oral drug design. Its inclusion in an H₂ health database appears to be a keyword-matching artefact (the word „hydrogen“ in the context of hydrogen bonding). Readers interested in H₂ therapy should disregard this entry.", "abstract": "The rule of five (Ro5), based on physicochemical profiles of phase II drugs, is consistent with structural limitations in protein targets and the drug target ligands. Three of four parameters in Ro5 are fundamental to the structure of both target and drug binding sites. The chemical structure of the drug ligand depends on the ligand chemistry and design philosophy. Two extremes of chemical structure and design philosophy exist; ligands constructed in the medicinal chemistry synthesis laboratory without input from natural selection and natural product (NP) metabolites biosynthesized based on evolutionary selection. Exceptions to Ro5 are found mostly among NPs. Chemistry chameleon-like behavior of some NPs due to intra-molecular hydrogen bonding as exemplified by cyclosporine A is a strong contributor to NP Ro5 outliers. The fragment derived, drug Navitoclax is an example of the extensive expertise, resources, time and key decisions required for the rare discovery of a non-NP Ro5 outlier.", "conclusion": "Chemistry chameleon-like behavior of some NPs due to intra-molecular hydrogen bonding as exemplified by cyclosporine A is a strong contributor to NP Ro5 outliers. The fragment derived, drug Navitoclax is an example of the extensive expertise, resources, time and key decisions required for the rare discovery of a non-NP Ro5 outlier." }, { "pmid": "26642800", "year": 2016, "title": "Complementary therapies for bladder pain syndrome: a systematic review.", "title_en": null, "title_de": "Komplementäre Therapien beim Blasenschmerzsyndrom: eine systematische Übersichtsarbeit", "journal": "International urogynecology journal", "authors": "Verghese et al.", "author_search": "verghese verghese", "doi": "10.1007/s00192-015-2886-3", "doi_url": "https://doi.org/10.1007/s00192-015-2886-3", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/26642800/", "url": "https://h2medicine.org/studies/study-verghese-2016-complementary-therapies-bladder-pain/", "methods": [ "unspecified" ], "indications": [ "sports-exercise" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2016 · Verghese — Complementary therapies for bladder pain syndrome: a systematic review", "summary": "A systematic review of complementary treatments for bladder pain syndrome identified dietary management, acupuncture, and physical therapy as approaches with the most potential benefit — while hydrogen-rich therapy was among the interventions surveyed. The authors stress that all findings come from small studies, and that large, robust randomised trials are still lacking. (International Urogynecology Journal, 2016.)", "assessment": "This is a literature review, not an experiment — it aggregates and narratively describes existing small studies. Hydrogen-rich therapy is mentioned as one of several interventions surveyed, but the review provides no detailed analysis of the hydrogen-specific studies and draws no separate conclusions about it. The overall evidence level for all examined complementary therapies is low. No clinical recommendation for hydrogen therapy in bladder pain syndrome can be derived from this paper. Its value lies in signalling that the topic has entered systematic review literature, and in clearly identifying the need for larger, better-designed trials.", "abstract": "INTRODUCTION AND HYPOTHESIS: Bladder pain syndrome is a difficult condition to treat. The purpose of this systematic review is to assess the effectiveness of various complementary therapies available for treatment. METHODS: This review was conducted in adherence with Preferred Reporting Items for Systematic Reviews. Citations were retrieved using a comprehensive database search (from inception to July 2014: CINAHL, Cochrane, EMBASE, Medline and SIGEL and grey literature). Studies that fulfilled the inclusion criteria were selected. Eligibility consisted of women with bladder pain syndrome, an intervention of alternative/complementary therapies and an outcome of improvement of symptoms. Information regarding study characteristics and primary outcomes was collated. The Cochrane risk of bias scale was used to evaluate the quality of the studies included. RESULTS: A total of 1,454 citations were identified, 11 studies fulfilled the inclusion criteria (4 randomised control trials [RCTs] and 7 prospective studies). The key interventions studied were acupuncture, relaxation therapy, physical therapy, hydrogen-rich therapy, diet and nitric oxide synthetase. CONCLUSION: Therapies with the potential for benefit in patients with bladder pain syndrome are dietary management, acupuncture and physical therapy. These findings were obtained from small studies and hence caution is advised. Robustly designed multicentre RCTs on these complementary therapies are needed to guide patients and clinicians.", "conclusion": "Therapies with the potential for benefit in patients with bladder pain syndrome are dietary management, acupuncture and physical therapy. These findings were obtained from small studies and hence caution is advised. Robustly designed multicentre RCTs on these complementary therapies are needed to guide patients and clinicians." }, { "pmid": "27938540", "year": 2016, "title": "[Protective effect of hydrogen on the lung of sanitation workers exposed to haze].", "title_en": null, "title_de": "Schützende Wirkung von Wasserstoff auf die Lunge von Reinigungsarbeitern, die Smog ausgesetzt sind.", "journal": "Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases", "authors": "Gong et al.", "author_search": "gong gong", "doi": "10.3760/cma.j.issn.1001-0939.2016.12.003", "doi_url": "https://doi.org/10.3760/cma.j.issn.1001-0939.2016.12.003", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/27938540/", "url": "https://h2medicine.org/studies/study-gong-2016-protective-lung-sanitation-workers/", "methods": [ "inhalation" ], "indications": [ "respiratory", "immune-system", "oxidative-stress" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2016 · Gong et al. — Protective effect of hydrogen on the lung of sanitation workers exposed to haze.", "summary": "In this randomized double-blind placebo-controlled trial with 96 sanitation workers chronically exposed to air pollution, daily inhalation of an H₂/O₂ mixture for 30 days improved lung function (FEV1, PEF), reduced airway inflammation markers (FeNO, IL-2, MMP-12), and improved respiratory symptoms such as cough — compared to a nitrogen/oxygen control. (Chinese Journal of Tuberculosis and Respiratory Diseases, 2016.)", "assessment": "One of the stronger RCTs in the H₂ inhalation literature, with a well-defined population, repeated measurement time points, objective lung function outcomes, and honest null reporting for non-significant markers. Limitations: the population is specific (haze-exposed workers in Shijiazhuang, January–February), limiting generalizability; the H₂/O₂ mixture concentration (67% H₂) is much higher than typical commercial devices; 30 days is a short observation window; long-term lung function effects are unknown. Still, this study provides one of the cleaner signals for H₂ inhalation in respiratory health.", "abstract": "Objective: To study the protective effect of hydrogen inhalation on the lungs of sanitation workers exposed to haze. Methods: In this randomized, double-blind, placebo controlled clinical trial, 96 sanitation workers living in Shijiazhuang urban area were recruited during January to February, 2016. All enrolled participants were randomized to 2 groups; the treatment group inhaled H2∶O2 mixture (66.67%∶33.33%) 1 hour per day for 30 days, while the control group inhaled N2∶O2 mixture (66.67%∶33.33%) 1 hour per day for 30 days. Respiratory symptoms were evaluated and fractional exhaled nitric oxide(FeNO), biochemical indexes, lung function were measured at baseline(the 0th day) and during treatment (the 8th day, 15th day, and 30th day). Results: (1)The FeNO levels of the treatment group (16±5)×109 were lower than those of the control group(21±14)×109 on 8th day of treatment, with significant difference(F=6.94, P<0.05). (2)The levels of FEV1 were significantly higher in participants from the treatment group as compared to the control group on both 8th [(96±13)% vs(94±14)%(F=3.96, P<0.05)] and 30th day [(97±14)% vs (95±12)%(F=8.5, P<0.05)] of treatment, while PEF was also increased on 15th day [(73±15)% vs(67±18)%(F=8.68, P<0.05)]. (3)The sputum levels of MMP-12 and SOD3 were consistently lower in the treatment group as compared to the control group at each time point, and the levels of IL-10 were higher in the treatment group as compared to the control group on the 15th and 30th day. MDA and IL-2 levels were lower in the treatment group than in the control group on the 30th day(P<0.05). The sputum levels of CRP and TGF-β1 at each time point were not different between the 2 groups (P>0.05). (4)The serum levels of IL-2 and SOD3 were lower in the treatment group as compared to the control group while IL-10 was higher than in the control group at each time point, and MMP-12 was lower in the treatment group than that in the control group on the 30th day(P<0.05). The relative ratios of CRP, TGF-β1 and MDA in serum at each time point between the 2 groups were not significantly different (P>0.05). (5)Hydrogen inhalation improved respiratory symptoms such as cough. Conclusions: Inhalation of hydrogen gas could alleviate airway inflammation and oxidative stress of sanitation workers exposed to air pollution. There was even a significant inhibitory effect on the level of systemic inflammatory response. Importantly, inhalation of hydrogen could improve respiratory symptoms such as cough.", "conclusion": "Inhalation of hydrogen gas could alleviate airway inflammation and oxidative stress of sanitation workers exposed to air pollution. There was even a significant inhibitory effect on the level of systemic inflammatory response. Importantly, inhalation of hydrogen could improve respiratory symptoms such as cough." }, { "pmid": "27176725", "year": 2016, "title": "A randomized double-blind multi-center trial of hydrogen water for Parkinson's disease: protocol and baseline characteristics.", "title_en": null, "title_de": "Eine randomisierte doppelblinde multizentrische Studie zu Wasserstoffwasser bei Morbus Parkinson: Protokoll und Ausgangscharakteristika.", "journal": "BMC neurology", "authors": "Yoritaka et al.", "author_search": "yoritaka yoritaka", "doi": "10.1186/s12883-016-0589-0", "doi_url": "https://doi.org/10.1186/s12883-016-0589-0", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/27176725/", "url": "https://h2medicine.org/studies/study-yoritaka-2016-multi-center-parkinson-disease/", "methods": [ "drinking-hrw" ], "indications": [ "neurology" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2016 · Yoritaka et al. — A randomized double-blind multi-center trial of hydrogen water for Parkinson's disease: protocol and baseline characteristics.", "summary": "This publication reports the protocol and baseline characteristics of a large multi-center RCT (n=178, 14 hospitals) designed to confirm whether 1000 mL/day of H₂ water can improve Parkinson's disease symptoms, as suggested by a prior smaller study. The primary endpoint is the change in total UPDRS score over 72 weeks. (BMC Neurology, 2016.)", "assessment": "This is a protocol/baseline paper, not an efficacy report. Its value lies in demonstrating that the H₂-Parkinson hypothesis has been taken seriously enough to design a large, methodologically rigorous confirmatory trial. Important: the results of this trial are not contained in this paper — readers should seek the subsequent outcome publication. The prior smaller study was positive; whether this larger confirmatory trial replicates that result is the key open question.", "abstract": "BACKGROUND: Our previous randomized double-blind study showed that drinking hydrogen (H2) water for 48 weeks significantly improved the total Unified Parkinson's Disease Rating Scale (UPDRS) score of Parkinson's disease (PD) patients treated with levodopa. We aim to confirm this result using a randomized double-blind placebo-controlled multi-center trial. METHODS: Changes in the total UPDRS scores from baseline to the 8(th), 24(th), 48(th), and 72(nd) weeks, and after the 8(th) week, will be evaluated. The primary endpoint of the efficacy of this treatment in PD is the change in the total UPDRS score from baseline to the 72(nd) week. The changes in UPDRS part II, UPDRS part III, each UPDRS score, PD Questionnaire-39 (PDQ-39), and the modified Hoehn and Yahr stage at these same time-points, as well as the duration until the protocol is finished because additional levodopa is required or until the disease progresses, will also be analyzed. Adverse events and screening laboratory studies will also be examined. Participants in the hydrogen water group will drink 1000 mL/day of H2 water, and those in the placebo water group will drink normal water. One-hundred-and-seventy-eight participants with PD (88 women, 90 men; mean age: 64.2 [SD 9.2] years, total UPDRS: 23.7 [11.8], with levodopa medication: 154 participants, without levodopa medication: 24 participants; daily levodopa dose: 344.1 [202.8] mg, total levodopa equivalent dose: 592.0 [317.6] mg) were enrolled in 14 hospitals and were randomized. DISCUSSION: This study will confirm whether H2 water can improve PD symptoms. TRIAL REGISTRATION: UMIN000010014 (February, 13, 2013).", "conclusion": "DISCUSSION: This study will confirm whether H2 water can improve PD symptoms. TRIAL REGISTRATION: UMIN000010014 (February, 13, 2013)." }, { "pmid": "27606690", "year": 2016, "title": "Hydrogen-Rich Saline as an Innovative Therapy for Cataract: A Hypothesis.", "title_en": null, "title_de": "Wasserstoffreiche Kochsalzlösung als innovative Therapie bei Katarakt: Eine Hypothese", "journal": "Medical science monitor : international medical journal of experimental and clinical research", "authors": "Qin et al.", "author_search": "qin qin", "doi": "10.12659/msm.899807", "doi_url": "https://doi.org/10.12659/msm.899807", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/27606690/", "url": "https://h2medicine.org/studies/study-qin-2016-saline-innovative-cataract-hypothesis/", "methods": [ "saline-iv" ], "indications": [ "metabolic", "eye", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2016 · Qin — Hydrogen-Rich Saline as an Innovative Therapy for Cataract: A Hypothesis", "summary": "This paper proposes a theoretical rationale for using molecular hydrogen as an antioxidant to protect against cataract formation — based on H₂'s known ability to selectively neutralise damaging reactive oxygen species (ROS). No experiments are reported; this is a hypothesis article outlining a plausible mechanism for future investigation. (Medical Science Monitor, 2016.)", "assessment": "This is a theoretical hypothesis paper — it contains no experimental data whatsoever. No human, animal, or cell experiments are reported. The proposed mechanism is biologically plausible and internally consistent with published H₂ pharmacology, but speculation is not evidence. No conclusion about the clinical usefulness of hydrogen therapy for cataract can be drawn from this article. It is a starting point for future research, not proof of efficacy.", "abstract": "Cataract is the leading cause of irreversible blindness worldwide. Increasing evidence indicates that oxidative stress is an important risk factor contributing to the development of cataract. Moreover, the enhancement of the antioxidant defense system may be beneficial to prevent or delay the cataractogenesis. The term oxidative stress has been defined as a disturbance in the equilibrium status of oxidant/antioxidant systems with progressive accumulation of reactive oxygen species (ROS) in intact cells. Superfluous ROS can damage proteins, lipids, polysaccharides, and nucleic acids within ocular tissues that are closely correlated with cataract formation. Therefore, prevention of oxidative stress damage by antioxidants might be considered as a viable means of medically offsetting the progression of this vision-impairing disease. Molecular hydrogen has recently been verified to have protective and therapeutic value as an antioxidant through its ability to selectively reduce cytotoxic ROS such as hydroxyl radical (OH). Hitherto, hydrogen has been used as a therapeutic element against multiple pathologies in both animal models and human patients. Unlike most well-known antioxidants, which are unable to successfully target organelles, hydrogen has advantageous distribution characteristics enabling it to penetrate biomembranes and diffuse into the cytosol, mitochondria, and nucleus. Consequently, we speculate that hydrogen might be an effective antioxidant to protect against lens damage, and it is important to further explore the biological mechanism underlying its potential therapeutic effects.", "conclusion": "Unlike most well-known antioxidants, which are unable to successfully target organelles, hydrogen has advantageous distribution characteristics enabling it to penetrate biomembranes and diffuse into the cytosol, mitochondria, and nucleus. Consequently, we speculate that hydrogen might be an effective antioxidant to protect against lens damage, and it is important to further explore the biological " }, { "pmid": "27598129", "year": 2016, "title": "New Approach in Translational Medicine: Effects of Electrolyzed Reduced Water (ERW) on NF-κB/iNOS Pathway in U937 Cell Line under Altered Redox State.", "title_en": null, "title_de": "Neuer Ansatz in der translationalen Medizin: Wirkungen von elektrolysiertem reduziertem Wasser (ERW) auf den NF-κB/iNOS-Signalweg in der U937-Zelllinie bei verändertem Redox-Zustand", "journal": "International journal of molecular sciences", "authors": "Franceschelli et al.", "author_search": "franceschelli franceschelli", "doi": "10.3390/ijms17091461", "doi_url": "https://doi.org/10.3390/ijms17091461", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/27598129/", "url": "https://h2medicine.org/studies/study-franceschelli-2016-approach-translational-medicine-electrolyzed/", "methods": [ "drinking-hrw" ], "indications": [ "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2016 · Franceschelli — New Approach in Translational Medicine: Effects of Electrolyzed Reduced Water (ERW) on NF-κB/iNOS Pathway in U937 Cell Line under Altered Redox State", "summary": "In a cell culture experiment, electrolyzed reduced water (ERW) — which contains dissolved molecular hydrogen — protected human immune cells (U937) against hydrogen-peroxide-induced oxidative damage by restoring antioxidant enzyme activity and reducing inflammatory signalling via the NF-κB/iNOS pathway. This is a laboratory finding in cells only, with no direct implications for human health. (International Journal of Molecular Sciences, 2016.)", "assessment": "This is a cell culture (in-vitro) study — results apply to U937 cells under artificial oxidative stress conditions, and cannot be directly extrapolated to humans. The mechanistic findings are scientifically interesting and consistent with other H₂ research on antioxidant and anti-inflammatory pathways. However, cell-line studies routinely do not translate to clinical efficacy, and this study provides no evidence of benefit in living organisms. No health claims for humans can be based on this paper alone.", "abstract": "It is known that increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) can exert harmful effects, altering the cellular redox state. Electrolyzed Reduced Water (ERW) produced near the cathode during water electrolysis exhibits high pH, high concentration of dissolved hydrogen and an extremely negative redox potential. Several findings indicate that ERW had the ability of a scavenger free radical, which results from hydrogen molecules with a high reducing ability and may participate in the redox regulation of cellular function. We investigated the effect of ERW on H₂O₂-induced U937 damage by evaluating the modulation of redox cellular state. Western blotting and spectrophotometrical analysis showed that ERW inhibited oxidative stress by restoring the antioxidant capacity of superoxide dismutase, catalase and glutathione peroxidase. Consequently, ERW restores the ability of the glutathione reductase to supply the cell of an important endogenous antioxidant, such as GSH, reversing the inhibitory effect of H₂O₂ on redox balance of U937 cells. Therefore, this means a reduction of cytotoxicity induced by peroxynitrite via a downregulation of the NF-κB/iNOS pathway and could be used as an antioxidant for preventive and therapeutic application. In conclusion, ERW can protect the cellular redox balance, reducing the risk of several diseases with altered cellular homeostasis such as inflammation.", "conclusion": "Therefore, this means a reduction of cytotoxicity induced by peroxynitrite via a downregulation of the NF-κB/iNOS pathway and could be used as an antioxidant for preventive and therapeutic application. In conclusion, ERW can protect the cellular redox balance, reducing the risk of several diseases with altered cellular homeostasis such as inflammation." }, { "pmid": "27558955", "year": 2016, "title": "Molecular hydrogen suppresses activated Wnt/β-catenin signaling.", "title_en": null, "title_de": "Molekularer Wasserstoff unterdrückt aktivierte Wnt/β-Catenin-Signalübertragung", "journal": "Scientific reports", "authors": "Lin et al.", "author_search": "lin lin", "doi": "10.1038/srep31986", "doi_url": "https://doi.org/10.1038/srep31986", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/27558955/", "url": "https://h2medicine.org/studies/study-lin-2016-suppresses-activated-wnt-catenin/", "methods": [ "drinking-hrw" ], "indications": [ "joints-rheumatology" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2016 · Lin — Molecular Hydrogen Suppresses Activated Wnt/β-catenin Signaling", "summary": "In cell culture and a rat osteoarthritis model, molecular hydrogen (H₂) suppressed abnormally activated Wnt/β-catenin signalling — a pathway implicated in cartilage breakdown — by promoting degradation of β-catenin, and tended to reduce cartilage loss in rats drinking H₂ water. These are preclinical findings in cells and animals; their relevance to human joint disease is not yet established. (Scientific Reports, 2016.)", "assessment": "This is a preclinical study combining cell culture and a rat animal model. The mechanistic finding — that H₂ can modulate a major oncogenic and pro-degenerative signalling pathway — is scientifically novel. However, the animal result is reported as a „tendency”, not a significant effect, and no human data are presented. Results in rats and cell cultures cannot be directly transferred to humans. This study identifies a potential new mechanism of action for H₂ that warrants further investigation, particularly for osteoarthritis and cancer-related signalling contexts.", "abstract": "Molecular hydrogen (H2) is effective for many diseases. However, molecular bases of H2 have not been fully elucidated. Cumulative evidence indicates that H2 acts as a gaseous signal modulator. We found that H2 suppresses activated Wnt/β-catenin signaling by promoting phosphorylation and degradation οf β-catenin. Either complete inhibition of GSK3 or mutations at CK1- and GSK3-phosphorylation sites of β-catenin abolished the suppressive effect of H2. H2 did not increase GSK3-mediated phosphorylation of glycogen synthase, indicating that H2 has no direct effect on GSK3 itself. Knock-down of adenomatous polyposis coli (APC) or Axin1, which form the β-catenin degradation complex, minimized the suppressive effect of H2 on β-catenin accumulation. Accordingly, the effect of H2 requires CK1/GSK3-phosphorylation sites of β-catenin, as well as the β-catenin degradation complex comprised of CK1, GSK3, APC, and Axin1. We additionally found that H2 reduces the activation of Wnt/β-catenin signaling in human osteoarthritis chondrocytes. Oral intake of H2 water tended to ameliorate cartilage degradation in a surgery-induced rat osteoarthritis model through attenuating β-catenin accumulation. We first demonstrate that H2 suppresses abnormally activated Wnt/β-catenin signaling, which accounts for the protective roles of H2 in a fraction of diseases.", "conclusion": "Oral intake of H2 water tended to ameliorate cartilage degradation in a surgery-induced rat osteoarthritis model through attenuating β-catenin accumulation. We first demonstrate that H2 suppresses abnormally activated Wnt/β-catenin signaling, which accounts for the protective roles of H2 in a fraction of diseases." }, { "pmid": "27531909", "year": 2016, "title": "Hydrogen Metabolism in Helicobacter pylori Plays a Role in Gastric Carcinogenesis through Facilitating CagA Translocation.", "title_en": null, "title_de": "Der Wasserstoffstoffwechsel in Helicobacter pylori spielt eine Rolle bei der Magenkarzinogenese durch Erleichterung der CagA-Translokation", "journal": "mBio", "authors": "Wang et al.", "author_search": "wang wang", "doi": "10.1128/mbio.01022-16", "doi_url": "https://doi.org/10.1128/mbio.01022-16", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/27531909/", "url": "https://h2medicine.org/studies/study-wang-2016-metabolism-helicobacter-pylori-plays/", "methods": [ "inhalation" ], "indications": [ "liver", "sports-exercise", "cancer", "respiratory", "immune-system" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2016 · Wang — Hydrogen Metabolism in Helicobacter pylori Plays a Role in Gastric Carcinogenesis through Facilitating CagA Translocation", "summary": "This animal and cell study shows that the bacterium Helicobacter pylori uses molecular hydrogen — produced by the gut microbiome — as an energy source to power delivery of its cancer-causing toxin CagA into stomach cells, promoting gastric cancer development in a gerbil model. Crucially, this concerns bacterial hydrogen metabolism, not therapeutic hydrogen intake by humans; the findings relate to a pathogen, not to H₂ supplementation. (mBio, 2016.)", "assessment": "This is a preclinical animal and cell study about the pathogen Helicobacter pylori — not about H₂ supplementation or hydrogen therapy. The finding that H. pylori exploits host-derived H₂ to power toxin delivery is scientifically significant for understanding gastric carcinogenesis and may open new treatment avenues. However, this paper has no bearing whatsoever on the safety or efficacy of molecular hydrogen consumed as a supplement — a completely different biological context. Results come from a gerbil model and a small number of clinical isolates (n=6 per group).", "abstract": "UNLABELLED: A known virulence factor of Helicobacter pylori that augments gastric cancer risk is the CagA cytotoxin. A carcinogenic derivative strain, 7.13, that has a greater ability to translocate CagA exhibits much higher hydrogenase activity than its parent noncarcinogenic strain, B128. A Δhyd mutant strain with deletion of hydrogenase genes was ineffective in CagA translocation into human gastric epithelial AGS cells, while no significant attenuation of cell adhesion was observed. The quinone reductase inhibitor 2-n-heptyl-4-hydroxyquinoline-N-oxide (HQNO) was used to specifically inhibit the H2-utilizing respiratory chain of outer membrane-permeabilized bacterial cells; that level of inhibitor also greatly attenuated CagA translocation into AGS cells, indicating the H2-generated transmembrane potential is a contributor to toxin translocation. The Δhyd strain showed a decreased frequency of DNA transformation, suggesting that H. pylori hydrogenase is also involved in energizing the DNA uptake apparatus. In a gerbil model of infection, the ability of the Δhyd strain to induce inflammation was significantly attenuated (at 12 weeks postinoculation), while all of the gerbils infected with the parent strain (7.13) exhibited a high level of inflammation. Gastric cancer developed in 50% of gerbils infected with the wild-type strain 7.13 but in none of the animals infected with the Δhyd strain. By examining the hydrogenase activities from well-defined clinical H. pylori isolates, we observed that strains isolated from cancer patients (n = 6) have a significantly higher hydrogenase (H2/O2) activity than the strains isolated from gastritis patients (n = 6), further supporting an association between H. pylori hydrogenase activity and gastric carcinogenesis in humans. IMPORTANCE: Hydrogen-utilizing hydrogenases are known to be important for some respiratory pathogens to colonize hosts. Here a gastric cancer connection is made via a pathogen's (H. pylori) use of molecular hydrogen, a host microbiome-produced gas. Delivery of the known carcinogenic factor CagA into host cells is augmented by the H2-utilizing respiratory chain of the bacterium. The role of hydrogenase in carcinogenesis is demonstrated in an animal model, whereby inflammation markers and cancer development were attenuated in the hydrogenase-null strain. Hydrogenase activity comparisons of clinical strains of the pathogen also support a connection between hydrogen metabolism and gastric cancer risk. While molecular hydrogen use is acknowledged to be an alternative high-energy substrate for some pathogens, this work extends the roles of H2 oxidation to include transport of a carcinogenic toxin. The work provides a new avenue for exploratory treatment of some cancers via microflora alterations.", "conclusion": "While molecular hydrogen use is acknowledged to be an alternative high-energy substrate for some pathogens, this work extends the roles of H2 oxidation to include transport of a carcinogenic toxin. The work provides a new avenue for exploratory treatment of some cancers via microflora alterations." }, { "pmid": "27477846", "year": 2016, "title": "Molecular Hydrogen Alleviates Cellular Senescence in Endothelial Cells.", "title_en": null, "title_de": "Molekularer Wasserstoff mildert zelluläre Seneszenz in Endothelzellen", "journal": "Circulation journal : official journal of the Japanese Circulation Society", "authors": "Hara et al.", "author_search": "hara hara", "doi": "10.1253/circj.cj-16-0227", "doi_url": "https://doi.org/10.1253/circj.cj-16-0227", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/27477846/", "url": "https://h2medicine.org/studies/study-hara-2016-alleviates-cellular-senescence-endothelial/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "cardiovascular", "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2016 · Hara — Molecular Hydrogen Alleviates Cellular Senescence in Endothelial Cells", "summary": "In human vascular endothelial cells exposed to a toxic compound (TCDD), hydrogen-rich medium prevented signs of cellular ageing (senescence) even after H₂ had dissipated from the medium — an effect mediated by the antioxidant transcription factor Nrf2. This is a cell culture study; results cannot be directly applied to human ageing or longevity. (Circulation Journal, 2016.)", "assessment": "This is an in-vitro cell study — results apply to human umbilical vein endothelial cells under an artificially induced toxic stress, and cannot be extrapolated to human vascular ageing or longevity. The Nrf2-mediated mechanism identified is scientifically plausible and consistent with other H₂ research, and the persistence of effect after H₂ dissipation is a mechanistically interesting observation. However, no conclusions about anti-ageing effects in living humans can be drawn from this experiment. Claims that „hydrogen-rich water increases longevity” (which the authors' discussion touches on) go well beyond what cell culture data can support.", "abstract": "BACKGROUND: Substantial evidence indicates that molecular hydrogen (H2) has beneficial vascular effects because of its antioxidant and/or anti-inflammatory effects. Thus, hydrogen-rich water may prove to be an effective anti-aging drink. This study examined the effects of H2on endothelial senescence and clarified the mechanisms involved. METHODS AND RESULTS: Hydrogen-rich medium was produced by a high-purity hydrogen gas generator. Human umbilical vein endothelial cells (HUVECs) were incubated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for various time periods in normal or hydrogen-rich medium. The baseline H2concentration in hydrogen-rich medium was 0.55±0.07 mmol/L. This concentration gradually decreased, and H2was almost undetectable in medium after 12 h. At 24 h after TCDD exposure, HUVECs treated with TCDD exhibited increased 8OHdG and acetyl-p53 expression, decreased nicotinamide adenine dinucleotide (NAD(+))/NADH ratio, impaired Sirt1 activity, and enhanced senescence-associated β-galactosidase. However, HUVECs incubated in hydrogen-rich medium did not exhibit these TCDD-induced changes accompanying Nrf2 activation, which was observed even after H2was undetectable in the medium. Chrysin, an inhibitor of Nrf2, abolished the protective effects of H2on HUVECs. CONCLUSIONS: H2has long-lasting antioxidant and anti-aging effects on vascular endothelial cells through the Nrf2 pathway, even after transient exposure to H2. Hydrogen-rich water may thus be a functional drink that increases longevity. (Circ J 2016; 80: 2037-2046).", "conclusion": "H2has long-lasting antioxidant and anti-aging effects on vascular endothelial cells through the Nrf2 pathway, even after transient exposure to H2. Hydrogen-rich water may thus be a functional drink that increases longevity. (Circ J 2016; 80: 2037-2046)." }, { "pmid": "27448107", "year": 2016, "title": "Molecular hydrogen in human breath: a new strategy for selectively diagnosing peptic ulcer disease, non-ulcerous dyspepsia and Helicobacter pylori infection.", "title_en": null, "title_de": "Molekularer Wasserstoff in der menschlichen Atemluft: eine neue Strategie zur selektiven Diagnose von peptischem Ulkus, nicht-ulzeröser Dyspepsie und Helicobacter-pylori-Infektion.", "journal": "Journal of breath research", "authors": "Maity et al.", "author_search": "maity maity", "doi": "10.1088/1752-7155/10/3/036007", "doi_url": "https://doi.org/10.1088/1752-7155/10/3/036007", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/27448107/", "url": "https://h2medicine.org/studies/study-maity-2016-breath-strategy-selectively-diagnosing/", "methods": [], "indications": [ "respiratory" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "breath-test", "headline": "2016 · Maity et al. — Molecular hydrogen in human breath: a new strategy for selectively diagnosing peptic ulcer disease, non-ulcerous dyspepsia and Helicobacter pylori infection.", "summary": "This study shows that breath H₂ excretion profiles are distinctly altered by H. pylori activity and can non-invasively differentiate between peptic ulcer disease and non-ulcerous dyspepsia — even after H. pylori eradication — where the standard ¹³C-urea breath test fails to distinguish disease states. (Journal of Breath Research, 2016.)", "assessment": "An innovative diagnostic study using H₂ breath analysis as a disease classifier — not a therapeutic intervention. The clinical implications are real: a non-invasive breath test that distinguishes PUD from NUD and works post-eradication fills a diagnostic gap. Limitations: the study is mechanistic/proof-of-concept in nature; sample sizes per disease category are not clearly reported in the abstract; validation in larger independent cohorts is needed before clinical adoption. This paper fits a research overview website, but its framing must be clearly diagnostic, not therapeutic.", "abstract": "The gastric pathogen Helicobacter pylori utilizes molecular hydrogen (H2) as a respiratory substrate during colonization in the gastric mucosa. However, the link between molecular H2 and the pathogenesis of peptic-ulcer disease (PUD) and non-ulcerous dyspepsia (NUD) by the enzymatic activity of H. pylori still remains mostly unknown. Here we provide evidence that breath H2 excretion profiles are distinctly altered by the enzymatic activity of H. pylori for individuals with NUD and PUD. We subsequently unravelled the potential molecular mechanisms responsible for the alteration of H2 in exhaled breath in association with peptic ulcers, encompassing both gastric and duodenal ulcers, along with NUD. We also established that carbon-isotopic fractionations in the acid-mediated bacterial environment regulated by bacterial urease activity cannot discriminate the actual disease state i.e. whether it is peptic ulcer or NUD. However, our findings illuminate the unusual molecular H2 in breath that can track the precise evolution of PUD and NUD, even after the eradication of H. pylori infection. This deepens our understanding of the pathophysiology of PUD and NUD, reveals non-invasively the actual disease state in real-time and thus offers a novel and robust new-generation strategy for treating peptic-ulcer disease together with non-ulcer related complications even when the existing (13)C-urea breath test ((13)C-UBT) fails to diagnose.", "conclusion": "pylori infection. This deepens our understanding of the pathophysiology of PUD and NUD, reveals non-invasively the actual disease state in real-time and thus offers a novel and robust new-generation strategy for treating peptic-ulcer disease together with non-ulcer related complications even when the existing (13)C-urea breath test ((13)C-UBT) fails to diagnose." }, { "pmid": "27344261", "year": 2016, "title": "A revision in hydrogen isotopic composition of USGS42 and USGS43 human-hair stable isotopic reference materials for forensic science.", "title_en": null, "title_de": "Eine Revision der Wasserstoff-Isotopenzusammensetzung der stabilen Isotopen-Referenzmaterialien USGS42 und USGS43 aus menschlichem Haar für die forensische Wissenschaft", "journal": "Forensic science international", "authors": "Coplen et al.", "author_search": "coplen coplen", "doi": "10.1016/j.forsciint.2016.05.029", "doi_url": "https://doi.org/10.1016/j.forsciint.2016.05.029", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/27344261/", "url": "https://h2medicine.org/studies/study-coplen-2016-revision-isotopic-composition-usgs42/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2016 · Coplen — A revision in hydrogen isotopic composition of USGS42 and USGS43 human-hair stable isotopic reference materials for forensic science", "summary": "This analytical chemistry paper revises the certified hydrogen isotope values of two international reference materials (USGS42 and USGS43) made from human hair, used in forensic stable isotope analysis. The revision corrects systematic measurement errors caused by hydrogen cyanide formation in older analytical methods. This paper has no connection to molecular hydrogen therapy or health applications. (Forensic Science International, 2016.)", "assessment": "This paper is an analytical chemistry / forensic metrology study with no connection to molecular hydrogen as a health or therapeutic topic. The word „hydrogen” here refers to hydrogen stable isotopes used as forensic tracers — entirely different from H₂ supplementation biology. This paper does not provide any evidence for or against health effects of molecular hydrogen consumption. It is included in this database for completeness of the H₂ literature landscape, not as evidence of therapeutic relevance.", "abstract": "The hydrogen isotopic composition (δ(2)HVSMOW-SLAP) of USGS42 and USGS43 human hair stable isotopic reference materials, normalized to the VSMOW (Vienna-Standard Mean Ocean Water)-SLAP (Standard Light Antarctic Precipitation) scale, was originally determined with a high temperature conversion technique using an elemental analyzer (TC/EA) with a glassy carbon tube and glassy carbon filling and analysis by isotope-ratio mass spectrometer (IRMS). However, the TC/EA IRMS method can produce inaccurate δ(2)HVSMOW-SLAP results when analyzing nitrogen-bearing organic substances owing to the formation of hydrogen cyanide (HCN), leading to non-quantitative conversion of a sample into molecular hydrogen (H2) for IRMS analysis. A single-oven, chromium-filled, elemental analyzer (Cr-EA) coupled to an IRMS substantially improves the measurement quality and reliability of hydrogen isotopic analysis of hydrogen- and nitrogen-bearing organic material because hot chromium scavenges all reactive elements except hydrogen. USGS42 and USGS43 human hair isotopic reference materials have been analyzed with the Cr-EA IRMS method, and the δ(2)HVSMOW-SLAP values of their non-exchangeable hydrogen fractions have been revised: [Formula: see text] [Formula: see text] where mUr=0.001=‰. On average, these revised δ(2)HVSMOW-SLAP values are 5.7mUr more positive than those previously measured. It is critical that readers pay attention to the δ(2)HVSMOW-SLAP of isotopic reference materials in publications as they may need to adjust the δ(2)HVSMOW-SLAP measurement results of human hair in previous publications to ensure all results are on the same isotope-delta scale.", "conclusion": "On average, these revised δ(2)HVSMOW-SLAP values are 5.7mUr more positive than those previously measured. It is critical that readers pay attention to the δ(2)HVSMOW-SLAP of isotopic reference materials in publications as they may need to adjust the δ(2)HVSMOW-SLAP measurement results of human hair in previous publications to ensure all results are on the same isotope-delta scale." }, { "pmid": "27334126", "year": 2016, "title": "Feasibility and Safety of Hydrogen Gas Inhalation for Post-Cardiac Arrest Syndrome　- First-in-Human Pilot Study.", "title_en": null, "title_de": "Durchführbarkeit und Sicherheit der Wasserstoffgas-Inhalation beim Post-Cardiac-Arrest-Syndrom — erste Pilotstudie am Menschen.", "journal": "Circulation journal : official journal of the Japanese Circulation Society", "authors": "Tamura et al.", "author_search": "tamura tamura", "doi": "10.1253/circj.cj-16-0127", "doi_url": "https://doi.org/10.1253/circj.cj-16-0127", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/27334126/", "url": "https://h2medicine.org/studies/study-tamura-2016-feasibility-inhalation-post-cardiac/", "methods": [ "inhalation" ], "indications": [ "neurology", "fundamentals-safety" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2016 · Tamura et al. — Feasibility and Safety of Hydrogen Gas Inhalation for Post-Cardiac Arrest Syndrome — First-in-Human Pilot Study.", "summary": "In this first-in-human pilot study, 5 out-of-hospital cardiac arrest patients who achieved spontaneous circulation received H₂ gas inhalation combined with standard temperature management — no adverse effects were observed, and 4 of 5 patients survived 90 days with favorable neurological outcomes. This is an exploratory safety study, not a controlled efficacy trial. (Circulation Journal, 2016.)", "assessment": "A critical safety and feasibility study in one of the most challenging emergency medicine indications. With n=5 and no control arm, no efficacy conclusions are possible — but the absence of safety signals is meaningful given the severity of the patient population and the novelty of the intervention. Limitations: extremely small n; no randomization; heavy selection bias from 107 → 21 → 5; survival outcomes in PCAS are inherently variable. The study correctly frames itself as a first step toward a powered RCT.", "abstract": "BACKGROUND: Hydrogen gas inhalation (HI) ameliorates cerebral and cardiac dysfunction in animal models of post-cardiac arrest syndrome (PCAS). HI for human patients with PCAS has never been studied. METHODS AND RESULTS: Between January 2014 and January 2015, 21 of 107 patients with out-of-hospital cardiac arrest achieved spontaneous return of circulation. After excluding 16 patients with specific criteria, 5 patients underwent HI together with target temperature management (TTM). No undesirable effects attributable to HI were observed and 4 patients survived 90 days with a favorable neurological outcome. CONCLUSIONS: HI in combination with TTM is a feasible therapy for patients with PCAS. (Circ J 2016; 80: 1870-1873).", "conclusion": "HI in combination with TTM is a feasible therapy for patients with PCAS. (Circ J 2016; 80: 1870-1873)." }, { "pmid": "27123663", "year": 2016, "title": "H2 metabolism is widespread and diverse among human colonic microbes.", "title_en": null, "title_de": "Der H₂-Metabolismus ist unter menschlichen Kolonmikroben weit verbreitet und vielfältig", "journal": "Gut microbes", "authors": "Wolf et al.", "author_search": "wolf wolf", "doi": "10.1080/19490976.2016.1182288", "doi_url": "https://doi.org/10.1080/19490976.2016.1182288", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/27123663/", "url": "https://h2medicine.org/studies/study-wolf-2016-metabolism-widespread-diverse-among/", "methods": [ "unspecified" ], "indications": [ "metabolic", "sports-exercise", "eye", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2016 · Wolf — H₂ metabolism is widespread and diverse among human colonic microbes", "summary": "A large-scale genomic and metagenomic analysis shows that 70% of microbial species in the human colon encode genes for metabolising molecular hydrogen (H₂), and that electron-bifurcating fermentation — rather than respiratory H₂ oxidation — is the dominant mechanism of H₂ recycling in the gut. This is a bioinformatics and microbiome study; it characterises natural gut H₂ cycling, not exogenous H₂ supplementation. (Gut Microbes, 2016.)", "assessment": "This is an in-vitro / bioinformatics microbiome study — it characterises endogenous gut hydrogen cycling using genomic and metagenomic data from healthy human stool samples. It provides no clinical intervention data and does not study exogenous H₂ supplementation. Results cannot be used to support or refute claims about the health benefits of H₂ supplementation. Its value is as a basic science foundation: understanding how the gut naturally cycles H₂ is relevant background for interpreting how oral H₂ consumption might interact with the microbiome.", "abstract": "Microbial molecular hydrogen (H2) cycling is central to metabolic homeostasis and microbial composition in the human gastrointestinal tract. Molecular H2 is produced as an endproduct of carbohydrate fermentation and is reoxidised primarily by sulfate-reduction, acetogenesis, and methanogenesis. However, the enzymatic basis for these processes is incompletely understood and the hydrogenases responsible have not been investigated. In this work, we surveyed the genomic and metagenomic distribution of hydrogenase-encoding genes in the human colon to infer dominant mechanisms of H2 cycling. The data demonstrate that 70% of gastrointestinal microbial species listed in the Human Microbiome Project encode the genetic capacity to metabolise H2. A wide variety of anaerobically-adapted hydrogenases were present, with [FeFe]-hydrogenases predominant. We subsequently analyzed the hydrogenase gene content of stools from 20 healthy human subjects. The hydrogenase gene content of all samples was overwhelmingly dominated by fermentative and electron-bifurcating [FeFe]-hydrogenases emerging from the Bacteroidetes and Firmicutes. This study supports that H2 metabolism in the human gut is driven by fermentative H2 production and interspecies H2 transfer. However, it suggests that electron-bifurcation rather than respiration is the dominant mechanism of H2 reoxidation in the human colon, generating reduced ferredoxin to sustain carbon-fixation (e.g. acetogenesis) and respiration (via the Rnf complex). This work provides the first comprehensive bioinformatic insight into the mechanisms of H2 metabolism in the human colon.", "conclusion": "acetogenesis) and respiration (via the Rnf complex). This work provides the first comprehensive bioinformatic insight into the mechanisms of H2 metabolism in the human colon." }, { "pmid": "26947809", "year": 2016, "title": "Dock 'n roll: folding of a silk-inspired polypeptide into an amyloid-like beta solenoid.", "title_en": null, "title_de": "Dock 'n roll: Faltung eines seiden-inspirierten Polypeptids in ein amyloidähnliches Beta-Solenoid", "journal": "Soft matter", "authors": "Zhao et al.", "author_search": "zhao zhao", "doi": "10.1039/c6sm00169f", "doi_url": "https://doi.org/10.1039/c6sm00169f", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/26947809/", "url": "https://h2medicine.org/studies/study-zhao-2016-dock-roll-folding-silk/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2016 · Zhao — Dock 'n roll: folding of a silk-inspired polypeptide into an amyloid-like beta solenoid", "summary": "This computational chemistry and molecular dynamics study analyses how a silk-inspired polypeptide folds into a stable beta-solenoid structure — a question in structural biology and materials science. The „hydrogen” in this paper refers exclusively to hydrogen bonds within protein structures, not to molecular hydrogen (H₂) as a therapeutic or biological gas. This paper has no relevance to H₂ supplementation or health. (Soft Matter, 2016.)", "assessment": "This paper is a structural/computational chemistry study in materials science and soft matter physics. It has no connection to molecular hydrogen (H₂) as a biological or therapeutic agent. The „hydrogen” in this paper refers to hydrogen atoms forming intramolecular bonds within polypeptide structures. This paper provides no evidence relevant to H₂ health research. It appears in this database because of a keyword match on „hydrogen” in the literature search — it is not relevant to hydrogen therapy.", "abstract": "Polypeptides containing the motif ((GA)mGX)n occur in silk and have a strong tendency to self-assemble. For example, polypeptides containing (GAGAGAGX)n, where X = G or H have been observed to form filaments; similar sequences but with X = Q have been used in the design of coat proteins (capsids) for artificial viruses. The structure of the (GAGAGAGX)m filaments has been proposed to be a stack of peptides in a β roll structure with the hydrophobic side chains pointing outwards (hydrophobic shell). Another possible configuration, a β roll or β solenoid structure which has its hydrophobic side chains buried inside (hydrophobic core) was, however, overlooked. We perform ground state analysis as well as atomic-level molecular dynamics simulations, both on single molecules and on two-molecule stacks of the silk-inspired sequence (GAGAGAGQ)10, to decide whether the hydrophobic core or the hydrophobic shell configuration is the most stable one. We find that a stack of two hydrophobic core molecules is energetically more favorable than a stack of two hydrophobic shell molecules. A shell molecule initially placed in a perfect β roll structure tends to rotate its strands, breaking in-plane hydrogen bonds and forming out-of-plane hydrogen bonds, while a core molecule stays in the β roll structure. The hydrophobic shell structure has type II' β turns whereas the core configuration has type II β turns; only the latter secondary structure agrees well with solid-state NMR experiments on a similar sequence (GA)15. We also observe that the core stack has a higher number of intra-molecular hydrogen bonds and a higher number of hydrogen bonds between stack and water than the shell stack. Hence, we conclude that the hydrophobic core configuration is the most likely structure. In the stacked state, each peptide has more intra-molecular hydrogen bonds than a single folded molecule, which suggests that stacking provides the extra stability needed for molecules to reach the folded state.", "conclusion": "Hence, we conclude that the hydrophobic core configuration is the most likely structure. In the stacked state, each peptide has more intra-molecular hydrogen bonds than a single folded molecule, which suggests that stacking provides the extra stability needed for molecules to reach the folded state." }, { "pmid": "26927488", "year": 2016, "title": "Discovery of novel 2-phenyl-imidazo[1,2-a]pyridine analogues targeting tubulin polymerization as antiproliferative agents.", "title_en": null, "title_de": "Entdeckung neuartiger 2-Phenyl-imidazo[1,2-a]pyridin-Analoga, die auf die Tubulin-Polymerisation als antiproliferative Wirkstoffe abzielen", "journal": "European journal of medicinal chemistry", "authors": "An et al.", "author_search": "an an", "doi": "10.1016/j.ejmech.2016.02.004", "doi_url": "https://doi.org/10.1016/j.ejmech.2016.02.004", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/26927488/", "url": "https://h2medicine.org/studies/study-an-2016-discovery-phenyl-imidazo-pyridine/", "methods": [ "unspecified" ], "indications": [ "cancer" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2016 · An — Discovery of novel 2-phenyl-imidazo[1,2-a]pyridine analogues targeting tubulin polymerization as antiproliferative agents", "summary": "This medicinal chemistry study reports the synthesis and cancer-cell testing of new imidazo-pyridine compounds that inhibit tubulin polymerization — an approach to blocking cancer cell division. The paper has no connection to molecular hydrogen (H₂) therapy; it concerns synthetic organic chemistry and cancer pharmacology. (European Journal of Medicinal Chemistry, 2016.)", "assessment": "This paper is a medicinal chemistry / cancer pharmacology study with no relevance to molecular hydrogen (H₂) as a biological or therapeutic gas. It concerns synthetic tubulin polymerization inhibitors tested in cell culture. This paper provides no evidence relevant to H₂ health research. It appears in this database due to a keyword indexing overlap and is not relevant to hydrogen therapy.", "abstract": "A series of 2-aryl-imidazo-pyridines/pyrazines derivatives has been designed, synthesized and evaluated for their biological activities. Among them, several investigated compounds (1a, 3b and 3d) displayed potent antiproliferative activity against HeLa cell, and also displayed comparable tubulin polymerization inhibitory activity to colchicine. These studies provided a new molecular scaffold for the further development of antitumor agents that target tubulin.", "conclusion": "Among them, several investigated compounds (1a, 3b and 3d) displayed potent antiproliferative activity against HeLa cell, and also displayed comparable tubulin polymerization inhibitory activity to colchicine. These studies provided a new molecular scaffold for the further development of antitumor agents that target tubulin." }, { "pmid": "29917336", "year": 2016, "title": "[Effects of hydrogen-rich medium on lipopolysaccharide-induced intestinal epithelial barrier dysfunction of human colon carcinoma cells].", "title_en": null, "title_de": "Wirkungen von wasserstoffreichem Medium auf die lipopolysaccharid-induzierte Funktionsstörung der intestinalen Epithelbarriere menschlicher Kolonkarzinomzellen", "journal": "Zhonghua wei zhong bing ji jiu yi xue", "authors": "Yang et al.", "author_search": "yang yang", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/29917336/", "url": "https://h2medicine.org/studies/study-yang-2016-medium-lipopolysaccharide-induced-intestinal/", "methods": [ "saline-iv" ], "indications": [ "cancer", "pregnancy" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2016 · Yang — Effects of hydrogen-rich medium on lipopolysaccharide-induced intestinal epithelial barrier dysfunction of human colon carcinoma cells", "summary": "In a cell culture model of the intestinal epithelial barrier, hydrogen-rich medium protected Caco2 cells from lipopolysaccharide (LPS)-induced barrier disruption by improving cell viability, reducing cell injury, and partially restoring the expression and structure of tight-junction proteins claudin-1 and occludin. This is a laboratory study in colon cancer-derived cells; results cannot be directly applied to human intestinal health. (Zhonghua Wei Zhong Bing Ji Jiu Yi Xue, 2016.)", "assessment": "This is an in-vitro cell study using a colon adenocarcinoma cell line (Caco2) as a model of intestinal permeability. The observed protective effects of hydrogen-rich medium on LPS-induced barrier dysfunction are consistent with the known anti-inflammatory profile of H₂, and the use of TEER and tight-junction protein expression provides a mechanistically relevant readout. However, Caco2 cells are derived from cancer and represent a simplified, artificial model — results cannot be extrapolated to human gut health or intestinal disease. This study contributes to the mechanistic evidence base but requires follow-up in animal and eventually human models.", "abstract": "OBJECTIVE: To investigate the effects of hydrogen-rich medium on lipopolysaccharide (LPS)-induced intestinal epithelial barrier dysfunction of human intestinal epithelial (Caco2) cells. METHODS: Caco2 cells (passages 28-35) were purchased from the Cell Bank of the Shanghai Institute of Cell Biology, Chinese Academy of Sciences in Shanghai, China, and they were cultured in Dulbecco minimum essential medium (DMEM) containing 20% fetal bovine serum. These cells were randomly divided into four groups: control group (group A), hydrogen-rich medium group (group B), LPS group (group C) and LPS + hydrogen-rich medium group (group D). Cells were cultured with normal medium in group A and group C or with hydrogen-rich medium in group B and group D. Meanwhile, 1 g/L LPS was simultaneously added into group C and group D, while an equivalent volume of normal saline was added into group A and group B instead. In vitro intestinal epithelial models were reproduced with monolayer filter-grown Caco2 and intestinal epithelium. The trans-epithelial electrical resistance (TEER) in models of each group was measured at different incubation times (0, 3, 6, 12, 24 and 48 hours). Cell viability and cytotoxicity were assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) release assay, respectively, after incubation for 24 hours. The expression levels of claudin-1 and occludin were respectively determined at 6, 12 and 24 hours of incubation by Western Blot assay. The morphological structure of claudin-1 and occludin was respectively observed after incubation for 24 hours with immunofluorescence staining. RESULTS: There was no statistical significance in variables between group A and group B. Compared with group A, it was shown that TEER was time-dependently decreased in groups C and D after 6 hours. Compared with group C, TEER in group D was increased after 6 hours. Compared with group A, the cell viability was significantly reduced in group C [(67.2±7.9)% vs. (100.0±0.0)%, P < 0.05] and cell injury was obvious [LDH release rate: (38.5±2.1)% vs. (1.2±0.3)%, P < 0.05]; the expression levels of claudin-1 and occludin at 6, 12, 24 hours were significantly down-regulated [claudin-1 (gray value): 0.351±0.079, 0.272±0.075, 0.190±0.049 vs. 0.518±0.030; occludin (gray value): 0.416±0.044, 0.290±0.062, 0.226±0.019 vs. 0.602±0.038, all P < 0.05], and the structure of claudin-1 and occludin were profoundly disrupted. Compared with group C, it was shown that the cell viability was significantly increased in group D [(88.8±7.4)% vs. (67.2±7.9)%, P < 0.05] and cell injury was significantly abated [LDH release rate: (16.4±4.3)% vs. (38.5±2.1)%, P < 0.05]; the expression levels of claudin-1 and occludin were significantly up-regulated at 24 hours [claudin-1 (gray value): 0.428±0.046 vs. 0.190±0.049, occludin (gray value): 0.466±0.071 vs. 0.226±0.019, both P < 0.05]; the disrupted structures of claudin-1 and occludin were partially recovered. CONCLUSION: Hydrogen-rich medium can effectively attenuate LPS-induced dysfunction of intestinal epithelial barrier in human Caco2 cells by ameliorating cell viability as well as regulating claudin-1 and occludin expression and structure.", "conclusion": "Hydrogen-rich medium can effectively attenuate LPS-induced dysfunction of intestinal epithelial barrier in human Caco2 cells by ameliorating cell viability as well as regulating claudin-1 and occludin expression and structure." }, { "pmid": "26912054", "year": 2016, "title": "Optically-Induced Cell Fusion on Cell Pairing Microstructures.", "title_en": null, "title_de": "Optisch induzierte Zellfusion auf Zellpaarungs-Mikrostrukturen", "journal": "Scientific reports", "authors": "Yang et al.", "author_search": "yang yang", "doi": "10.1038/srep22036", "doi_url": "https://doi.org/10.1038/srep22036", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/26912054/", "url": "https://h2medicine.org/studies/study-yang-2016-optically-induced-cell-fusion/", "methods": [ "unspecified" ], "indications": [ "cancer" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2016 · Yang — Optically-Induced Cell Fusion on Cell Pairing Microstructures", "summary": "This bioengineering paper reports a new technique called optically-induced cell fusion (OICF) that uses light-patterned virtual electrodes on a photoconductive film to selectively fuse paired cells with high efficiency. The only connection to „hydrogen” is that the photoconductive film is made of „hydrogen-rich amorphous silicon” — a semiconductor material — which has no relationship to molecular hydrogen (H₂) as a biological or therapeutic agent. (Scientific Reports, 2016.)", "assessment": "This is a bioengineering / microfluidics technology paper with no relevance to molecular hydrogen (H₂) as a biological or therapeutic agent. The term „hydrogen-rich” in this context refers to a semiconductor material (hydrogenated amorphous silicon, a-Si:H) used as a photoconductive layer. This paper provides no evidence relevant to H₂ health research. It appears in this database due to keyword indexing overlap.", "abstract": "Cell fusion is a critical operation for numerous biomedical applications including cell reprogramming, hybridoma formation, cancer immunotherapy, and tissue regeneration. However, unstable cell contact and random cell pairings have limited efficiency and yields when utilizing traditional methods. Furthermore, it is challenging to selectively perform cell fusion within a group of cells. This study reports a new approach called optically-induced cell fusion (OICF), which integrates cell-pairing microstructures with an optically-induced, localized electrical field. By projecting light patterns onto a photoconductive film (hydrogen-rich, amorphous silicon) coated on an indium-tin-oxide (ITO) glass while an alternating current electrical field was applied between two such ITO glass slides, \"virtual\" electrodes could be generated that could selectively fuse pairing cells. At 10 kHz, a 57% cell paring rate and an 87% fusion efficiency were successfully achieved at a driving voltage of 20  V(pp), suggesting that this new technology could be promising for selective cell fusion within a group of cells.", "conclusion": "By projecting light patterns onto a photoconductive film (hydrogen-rich, amorphous silicon) coated on an indium-tin-oxide (ITO) glass while an alternating current electrical field was applied between two such ITO glass slides, \"virtual\" electrodes could be generated that could selectively fuse pairing cells. At 10 kHz, a 57% cell paring rate and an 87% fusion efficiency were successfully achieved " }, { "pmid": "26845501", "year": 2016, "title": "Hydrogen-rich water ameliorates bronchopulmonary dysplasia (BPD) in newborn rats.", "title_en": null, "title_de": "Wasserstoffreiches Wasser mildert die bronchopulmonale Dysplasie (BPD) bei neugeborenen Ratten", "journal": "Pediatric pulmonology", "authors": "Muramatsu et al.", "author_search": "muramatsu muramatsu", "doi": "10.1002/ppul.23386", "doi_url": "https://doi.org/10.1002/ppul.23386", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/26845501/", "url": "https://h2medicine.org/studies/study-muramatsu-2016-ameliorates-bronchopulmonary-dysplasia-bpd/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "cancer", "respiratory", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2016 · Muramatsu — Hydrogen-Rich Water Ameliorates Bronchopulmonary Dysplasia (BPD) in Newborn Rats", "summary": "Hydrogen-rich water given to pregnant and nursing rats reduced lung damage caused by a bacterial toxin in newborn animals. The H₂ treatment normalized abnormal alveolar enlargement, lowered oxidative and inflammatory markers, and preserved the expression of key lung-development genes. This is a preclinical animal study with no direct implications for human therapy. (Pediatric Pulmonology, 2016.)", "assessment": "This is a preclinical rat study — not a human trial. The findings are mechanistically interesting: H₂ appears to attenuate oxidative damage and preserve developmental gene programs in a neonatal lung-injury model. However, results in rodents cannot be directly transferred to premature human infants, whose lung physiology and BPD pathogenesis are more complex. The study uses a single model (LPS-induced BPD surrogate), and the H₂ was delivered via maternal drinking water — a translational route difficult to replicate clinically. No safety or dose-optimization data for neonatal humans exist. Bottom line: scientifically promising hypothesis-generating work; clinical relevance is entirely unproven.", "abstract": "Bronchopulmonary dysplasia (BPD) is characterized by developmental arrest of the alveolar tissue. Oxidative stress is causally associated with development of BPD. The effects of hydrogen have been reported in a wide range of disease models and human diseases especially caused by oxidative stress. We made a rat model of BPD by injecting lipopolysaccharide (LPS) into the amniotic fluid at E16.5. The mother started drinking hydrogen-rich water from E9.5 and also while feeding milk. Hydrogen normalized LPS-induced abnormal enlargement of alveoli at P7 and P14. LPS increased staining for nitrotyrosine and 8-OHdG of the lungs, and hydrogen attenuated the staining. At P1, LPS treatment decreased expressions of genes for FGFR4, VEGFR2, and HO-1 in the lungs, and hydrogen increased expressions of these genes. In contrast, LPS treatment and hydrogen treatment had no essential effect on the expression of SOD1. Inflammatory marker proteins of TNFα and IL-6 were increased by LPS treatment, and hydrogen suppressed them. Treatment of A549 human lung adenocarcinoma epithelial cells with 10% hydrogen gas for 24 hr decreased production of reactive oxygen species in both LPS-treated and untreated cells. Lack of any known adverse effects of hydrogen makes hydrogen a promising therapeutic modality for BPD. Pediatr Pulmonol. 2016; 51:928-935. © 2016 Wiley Periodicals, Inc.", "conclusion": "2016; 51:928-935. © 2016 Wiley Periodicals, Inc." }, { "pmid": "26777153", "year": 2016, "title": "How the imidazole ring modulates amyloid formation of islet amyloid polypeptide: A chemical modification study.", "title_en": null, "title_de": "Wie der Imidazolring die Amyloidbildung des Inselamyloid-Polypeptids moduliert: Eine chemische Modifikationsstudie", "journal": "Biochimica et biophysica acta", "authors": "Zhang et al.", "author_search": "zhang zhang", "doi": "10.1016/j.bbagen.2016.01.008", "doi_url": "https://doi.org/10.1016/j.bbagen.2016.01.008", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/26777153/", "url": "https://h2medicine.org/studies/study-zhang-2016-how-imidazole-ring-modulates/", "methods": [ "unspecified" ], "indications": [ "diabetes" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2016 · Zhang — How the Imidazole Ring Modulates Amyloid Formation of Islet Amyloid Polypeptide: A Chemical Modification Study", "summary": "This in-vitro biochemistry study investigated the role of a specific amino acid (histidine-18) in the misfolding of islet amyloid polypeptide (hIAPP), a protein linked to type 2 diabetes. The research used chemical modification to probe how the imidazole ring of His(18) influences amyloid fiber formation — but does not involve molecular hydrogen (H₂) as a therapeutic agent. (Biochimica et Biophysica Acta, 2016.)", "assessment": "This is an in-vitro protein chemistry study that investigates intramolecular hydrogen bonds within the hIAPP peptide structure — not molecular hydrogen (H₂) as a bioactive substance. Its inclusion in an H₂ database appears to be based on keyword overlap. The science is methodologically solid and relevant to understanding type 2 diabetes-related amyloid pathology, but it has no direct connection to hydrogen medicine or H₂ therapy. Findings should not be interpreted as supporting the therapeutic use of H₂ water or H₂ gas in diabetes.", "abstract": "BACKGROUND: The misfolding of human islet amyloid polypeptide (hIAPP) is an important pathological factor on the onset of type 2 diabetes. A number of studies have been focused on His(18), the only histidine of hIAPP, whose imidazole ring and the protonation state might impact hIAPP amyloid formation, but the exact mechanism remains unclear. METHODS: We used diethylpyrocarbonate (DEPC) to specifically modify His(18) and obtained mono-ethyloxyformylated hIAPP (DMI). Thioflavin T based fluorescence, transmission electronic microscopy, circular dichroism spectroscopy, fluorescence dye leakage, Fourier transform infrared spectroscopy and replica-exchange molecular dynamics (REMD) simulation were applied to study the impact of DEPC-modification on hIAPP amyloid formation. RESULTS: After an ethyl-acetate group was introduced to the His(18) of hIAPP by diethylpyrocarbonate (DEPC) modification, the pH dependent hIAPP fibrillation went to the opposite order and the number of intra-molecular hydrogen bonds decreased, while the possibility of His(18) participating in the formation of α-helical structures increased. Furthermore, the membrane-peptide interaction and ion-peptide interaction were both impaired. CONCLUSIONS: The intramolecular hydrogen bond formation by His(18) and the possibility of His(18) participating in the formation of α-helical structures greatly modulated the manner of hIAPP amyloid formation. The imidazole ring directly participates in the hIAPP-membrane/ion interaction. GENERAL SIGNIFICANCE: DEPC modification is an alternative approach to investigate the role of the imidazole ring during amyloid formation.", "conclusion": "The intramolecular hydrogen bond formation by His(18) and the possibility of His(18) participating in the formation of α-helical structures greatly modulated the manner of hIAPP amyloid formation. The imidazole ring directly participates in the hIAPP-membrane/ion interaction. GENERAL" }, { "pmid": "26739257", "year": 2016, "title": "Molecular hydrogen regulates gene expression by modifying the free radical chain reaction-dependent generation of oxidized phospholipid mediators.", "title_en": null, "title_de": "Molekularer Wasserstoff reguliert die Genexpression durch Modifikation der von der Radikalkettenreaktion abhängigen Erzeugung oxidierter Phospholipid-Mediatoren", "journal": "Scientific reports", "authors": "Iuchi et al.", "author_search": "iuchi iuchi", "doi": "10.1038/srep18971", "doi_url": "https://doi.org/10.1038/srep18971", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/26739257/", "url": "https://h2medicine.org/studies/study-iuchi-2016-regulates-gene-expression-modifying/", "methods": [ "inhalation" ], "indications": [ "metabolic", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2016 · Iuchi — Molecular Hydrogen Regulates Gene Expression by Modifying the Free Radical Chain Reaction-Dependent Generation of Oxidized Phospholipid Mediators", "summary": "Molecular hydrogen (H₂) may regulate gene expression not by directly targeting DNA or transcription factors, but by modifying how oxidized phospholipids are produced through free radical chain reactions. This in-vitro study suggests H₂ attenuates lipid peroxidation and thereby shapes calcium-dependent signaling and downstream gene activity. It is a cell and chemical study, not a human trial. (Scientific Reports, 2016.)", "assessment": "This is an in-vitro and cell-free chemistry study — not a clinical or animal study. It makes a mechanistically plausible and novel proposal: H₂ shapes gene expression indirectly by altering the oxidized phospholipid landscape, which then modulates Ca²⁺ signaling. The chemical evidence (linoleic acid autoxidation suppression) is solid. The cell microarray data is consistent but requires careful interpretation — hundreds of gene-expression changes from a complex phospholipid mix may reflect non-specific effects. The key limitation is that concentrations and conditions in cell culture systems rarely mirror in-vivo physiology. No human data; no clinical relevance can be drawn directly. Scientifically, this is valuable mechanistic groundwork.", "abstract": "We previously showed that H2 acts as a novel antioxidant to protect cells against oxidative stress. Subsequently, numerous studies have indicated the potential applications of H2 in therapeutic and preventive medicine. Moreover, H2 regulates various signal transduction pathways and the expression of many genes. However, the primary targets of H2 in the signal transduction pathways are unknown. Here, we attempted to determine how H2 regulates gene expression. In a pure chemical system, H2 gas (approximately 1%, v/v) suppressed the autoxidation of linoleic acid that proceeds by a free radical chain reaction, and pure 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphocholine (PAPC), one of the major phospholipids, was autoxidized in the presence or absence of H2. H2 modified the chemical production of the autoxidized phospholipid species in the cell-free system. Exposure of cultured cells to the H2-dependently autoxidized phospholipid species reduced Ca(2+) signal transduction and mediated the expression of various genes as revealed by comprehensive microarray analysis. In the cultured cells, H2 suppressed free radical chain reaction-dependent peroxidation and recovered the increased cellular Ca(2+), resulting in the regulation of Ca(2+)-dependent gene expression. Thus, H2 might regulate gene expression via the Ca(2+) signal transduction pathway by modifying the free radical-dependent generation of oxidized phospholipid mediators.", "conclusion": "In the cultured cells, H2 suppressed free radical chain reaction-dependent peroxidation and recovered the increased cellular Ca(2+), resulting in the regulation of Ca(2+)-dependent gene expression. Thus, H2 might regulate gene expression via the Ca(2+) signal transduction pathway by modifying the free radical-dependent generation of oxidized phospholipid mediators." }, { "pmid": "26714124", "year": 2016, "title": "Hydrogen-Rich Saline Attenuates Acute Kidney Injury After Liver Transplantation via Activating p53-Mediated Autophagy.", "title_en": null, "title_de": "Wasserstoffreiche Kochsalzlösung mildert akute Nierenschädigung nach Lebertransplantation durch Aktivierung der p53-vermittelten Autophagie", "journal": "Transplantation", "authors": "Du et al.", "author_search": "du du", "doi": "10.1097/tp.0000000000001052", "doi_url": "https://doi.org/10.1097/tp.0000000000001052", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/26714124/", "url": "https://h2medicine.org/studies/study-du-2016-saline-attenuates-acute-kidney/", "methods": [ "saline-iv" ], "indications": [ "liver", "kidney-dialysis", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2016 · Du — Hydrogen-Rich Saline Attenuates Acute Kidney Injury After Liver Transplantation via Activating p53-Mediated Autophagy", "summary": "In rats undergoing liver transplantation, hydrogen-rich saline (HRS) protected the kidneys from acute injury by reducing oxidative damage and cell death, with p53-mediated autophagy as a key mechanism. Blocking autophagy reversed H₂'s kidney-protective effect, confirming the pathway's importance. This is a preclinical animal study; no human transplant data exist. (Transplantation, 2016.)", "assessment": "This is a preclinical rat study — no human data. It is mechanistically detailed and well-controlled, identifying a specific signaling route (p53 → autophagy induction → anti-apoptosis → kidney protection) that H₂-rich saline appears to engage after liver transplantation. The chloroquine rescue experiment strengthens the causal claim. Limitations include: single species, single time point (6 hours), intraperitoneal saline administration (not how H₂ would be given clinically), and no dose-response data. AKI after liver transplantation in humans is multifactorial and the pathophysiology differs substantially from rat models. Clinical translation requires dedicated human safety and efficacy trials.", "abstract": "BACKGROUND: Acute kidney injury (AKI) impacts the survival of liver transplant recipients severely. To date, the related mechanism and effective therapy have not been rigorously explored. The present study aimed to explore the role of p53-mediated autophagy in the protective effect of hydrogen-rich saline (HRS) on AKI after orthotropic liver transplantation (OLT). METHODS: Adult male Sprague-Dawley rats were randomly allocated into four groups: sham, OLT, OLT with HRS (6 ml/kg) pretreatment (HS), OLT with HRS and chloroquine pretreatment (60 mg/kg) group (CQ). All the samples were collected 6 hours after reperfusion. The renal function and oxidative stress level were measured by biochemical and histopathologic examinations. The formation of autophagosome was observed by transmission electron microscopy. The apoptotic rate was determined by terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick-end labeling analysis. The expression of caspase-3, cytochrome c, p53, damage-regulated autophagy modulator, Becline-1, microtubule-associated protein light 3-II, p62, lysosome-associated membrane protein-2, and the phosphorylation of p53 were assayed by western blot assay. RESULTS: Compared with the OLT group, HRS dramatically attenuated the histopathologic damage, restored the renal function, and decreased the oxidative stress level. Simultaneously, HRS significantly ameliorated apoptosis by decreasing the apoptotic rate and inhibiting the expression of caspase-3 and cytochrome c in rats subjected to OLT. The expression of Becline-1 and microtubule-associated protein light 3-II were upregulated with the inhibition of p62 and lysosome-associated membrane protein-2. The inhibition of autophagy by chloroquine counteracted the renoprotective effects of HRS. CONCLUSIONS: HRS is able to protect against AKI after liver transplantation partly by reducing apoptosis, which is possibly involved in the modulation of p53-mediated autophagy.", "conclusion": "HRS is able to protect against AKI after liver transplantation partly by reducing apoptosis, which is possibly involved in the modulation of p53-mediated autophagy." }, { "pmid": "26657415", "year": 2016, "title": "Is melanin a source of bioactive molecular hydrogen?", "title_en": null, "title_de": "Ist Melanin eine Quelle bioaktiven molekularen Wasserstoffs?", "journal": "Pharmacological research", "authors": "Ostojic et al.", "author_search": "ostojic ostojic", "doi": "10.1016/j.phrs.2015.12.002", "doi_url": "https://doi.org/10.1016/j.phrs.2015.12.002", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/26657415/", "url": "https://h2medicine.org/studies/study-ostojic-2016-melanin-source-bioactive/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2016 · Ostojic — Is Melanin a Source of Bioactive Molecular Hydrogen?", "summary": "This theoretical paper proposes that melanin — the pigment in human skin, hair, and eyes — may act as a natural biological source of molecular hydrogen (H₂) in the body. It is a hypothesis paper with no experimental data; the abstract is not publicly available for this record. (Pharmacological Research, 2016.)", "assessment": "This is a theoretical/hypothesis paper — not an experimental study and not a human trial. The abstract is empty in this database record, making a complete scientific evaluation impossible here. The hypothesis that melanin could generate bioactive H₂ is novel and potentially interesting, but unverified. No experimental evidence, no clinical data, no conclusions about therapeutic H₂ can be drawn from this record. Readers interested in the full argument should consult the paper directly via its DOI (10.1016/j.phrs.2015.12.002).", "abstract": null, "conclusion": null }, { "pmid": "26631313", "year": 2016, "title": "Design and optimization of selective azaindole amide M1 positive allosteric modulators.", "title_en": null, "title_de": "Design und Optimierung selektiver Azaindolamid-M1-positiver allosterischer Modulatoren", "journal": "Bioorganic & medicinal chemistry letters", "authors": "Davoren et al.", "author_search": "davoren davoren", "doi": "10.1016/j.bmcl.2015.11.053", "doi_url": "https://doi.org/10.1016/j.bmcl.2015.11.053", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/26631313/", "url": "https://h2medicine.org/studies/study-davoren-2016-design-optimization-selective-azaindole/", "methods": [ "unspecified" ], "indications": [ "neurology", "fundamentals-safety" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2016 · Davoren — Design and Optimization of Selective Azaindole Amide M1 Positive Allosteric Modulators", "summary": "This drug-design study developed a new class of small-molecule compounds that selectively activate the M1 muscarinic receptor — a target relevant to cognitive impairment in schizophrenia and Alzheimer's disease. The intramolecular hydrogen bond in these azaindole amide compounds is a key structural element — not molecular hydrogen (H₂) as a bioactive substance. (Bioorganic & Medicinal Chemistry Letters, 2016.)", "assessment": "This is an in-vitro medicinal chemistry and pharmacology study with some in-vivo animal data for a small-molecule drug candidate. It has no connection to hydrogen medicine or H₂ therapy; the „hydrogen bond“ in the title refers to a classical intramolecular bond within the drug structure. The science is credible drug-discovery work for neurological targets, but it is entirely outside the scope of molecular hydrogen (H₂) research. Its inclusion in an H₂ database is a keyword-based false positive.", "abstract": "Selective activation of the M1 receptor via a positive allosteric modulator (PAM) is a new approach for the treatment of the cognitive impairments associated with schizophrenia and Alzheimer's disease. A novel series of azaindole amides and their key pharmacophore elements are described. The nitrogen of the azaindole core is a key design element as it forms an intramolecular hydrogen bond with the amide N-H thus reinforcing the bioactive conformation predicted by published SAR and our homology model. Representative compound 25 is a potent and selective M1 PAM that has well aligned physicochemical properties, adequate brain penetration and pharmacokinetic (PK) properties, and is active in vivo. These favorable properties indicate that this series possesses suitable qualities for further development and studies.", "conclusion": "Representative compound 25 is a potent and selective M1 PAM that has well aligned physicochemical properties, adequate brain penetration and pharmacokinetic (PK) properties, and is active in vivo. These favorable properties indicate that this series possesses suitable qualities for further development and studies." }, { "pmid": "26537817", "year": 2016, "title": "Treatment with Hydrogen-Rich Saline Delays Disease Progression in a Mouse Model of Amyotrophic Lateral Sclerosis.", "title_en": null, "title_de": "Behandlung mit wasserstoffreicher Kochsalzlösung verzögert das Fortschreiten der Erkrankung in einem Mausmodell der amyotrophen Lateralsklerose", "journal": "Neurochemical research", "authors": "Zhang et al.", "author_search": "zhang zhang", "doi": "10.1007/s11064-015-1750-7", "doi_url": "https://doi.org/10.1007/s11064-015-1750-7", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/26537817/", "url": "https://h2medicine.org/studies/study-zhang-2016-saline-delays-disease-progression/", "methods": [ "saline-iv" ], "indications": [ "neurology", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2016 · Zhang — Treatment with Hydrogen-Rich Saline Delays Disease Progression in a Mouse Model of Amyotrophic Lateral Sclerosis", "summary": "In a transgenic mouse model of ALS, hydrogen-rich saline (HRS) significantly delayed disease onset, prolonged survival, and protected motor neurons from oxidative damage and mitochondrial dysfunction. Classical antioxidants have repeatedly failed in ALS clinical trials; H₂ offers a mechanistically distinct profile. This is a preclinical animal study — no human ALS data exist for H₂. (Neurochemical Research, 2016.)", "assessment": "This is a preclinical mouse study — not a human clinical trial. The findings are encouraging: HRS delayed ALS progression in the standard SOD1-G93A model via a multi-target mitochondria-protective mechanism. The SOD1-G93A model is the most-used ALS model but represents only ~2 % of human ALS cases (familial SOD1 mutations), so generalizability to sporadic ALS is limited. Daily i.p. injections are not a realistic clinical route. No human safety or dose data exist for H₂ in ALS. These results justify further translational research but cannot be interpreted as evidence for H₂ efficacy in human ALS patients.", "abstract": "Amyotrophic lateral sclerosis (ALS) is the most frequent adult-onset motor neuron disease, and accumulating evidence indicates that oxidative mechanisms contribute to ALS pathology, but classical antioxidants have not performed well in clinical trials. The aim of this work was to investigate the effect of treatment with hydrogen molecule on the development of disease in mutant SOD1 G93A transgenic mouse model of ALS. Treatment of mutant SOD1 G93A mice with hydrogen-rich saline (HRS, i.p.) significantly delayed disease onset and prolonged survival, and attenuated loss of motor neurons and suppressed microglial and glial activation. Treatment of mutant SOD1 G93A mice with HRS inhibited the release of mitochondrial apoptogenic factors and the subsequent activation of downstream caspase-3. Furthermore, treatment of mutant SOD1 G93A mice with HRS reduced levels of protein carbonyl and 3-nitrotyrosine, and suppressed formation of reactive oxygen species (ROS), peroxynitrite, and malondialdehyde. Treatment of mutant SOD1 G93A mice with HRS preserved mitochondrial function, marked by restored activities of Complex I and IV, reduced mitochondrial ROS formation and enhanced mitochondrial adenosine triphosphate synthesis. In conclusion, hydrogen molecule may be neuroprotective against ALS, possibly through abating oxidative and nitrosative stress and preserving mitochondrial function.", "conclusion": "Treatment of mutant SOD1 G93A mice with HRS preserved mitochondrial function, marked by restored activities of Complex I and IV, reduced mitochondrial ROS formation and enhanced mitochondrial adenosine triphosphate synthesis. In conclusion, hydrogen molecule may be neuroprotective against ALS, possibly through abating oxidative and nitrosative stress and preserving mitochondrial function." }, { "pmid": "26529665", "year": 2016, "title": "HYDROGEN-RICH MEDIUM AMELIORATES LIPOPOLYSACCHARIDE-INDUCED BARRIER DYSFUNCTION VIA RHOA-MDIA1 SIGNALING IN CACO-2 CELLS.", "title_en": null, "title_de": "Wasserstoffreiches Medium mildert die lipopolysaccharid-induzierte Barrierefunktionsstörung über die RhoA-mDia1-Signalübertragung in Caco-2-Zellen", "journal": "Shock (Augusta, Ga.)", "authors": "Yang et al.", "author_search": "yang yang", "doi": "10.1097/shk.0000000000000503", "doi_url": "https://doi.org/10.1097/shk.0000000000000503", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/26529665/", "url": "https://h2medicine.org/studies/study-yang-2016-medium-ameliorates-lipopolysaccharide-induced/", "methods": [ "inhalation" ], "indications": [ "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2016 · Yang — Hydrogen-Rich Medium Ameliorates Lipopolysaccharide-Induced Barrier Dysfunction via RhoA-mDia1 Signaling in Caco-2 Cells", "summary": "In intestinal epithelial cells (Caco-2), hydrogen-rich medium protected the gut barrier from LPS-induced permeability increase by modulating the RhoA-mDia1 signaling pathway, which governs tight junction and adherens junction integrity. This is a mechanistically detailed in-vitro cell study relevant to sepsis-associated gut failure — not a human or animal experiment. (Shock, 2016.)", "assessment": "This is a rigorous in-vitro cell study that provides a plausible and specific molecular mechanism for how H₂ may protect the gut barrier during sepsis: RhoA suppression and mDia1 upregulation stabilize tight junctions and adherens junctions. The gene-knockdown controls strengthen the causal interpretation. Limitations: Caco-2 monolayers are a simplified single-cell-type model; the LPS dose is very high; results need validation in vivo (animal model) and then in humans before any clinical implications can be drawn. No human relevance can be directly claimed. Scientifically, this is a useful mechanistic piece in the H₂/sepsis puzzle.", "abstract": "Gastrointestinal barrier dysfunction is associated with the severity and prognosis of sepsis. Hydrogen gas (H2) can ameliorate multiple organ damage in septic animals. Ras homolog gene family member A (RhoA) and mammalian diaphanous-related formin 1 (mDia1) are important to regulate tight junction (TJ) and adherens junction (AJ), both of which determine the integrity of the intestinal barrier. This study was aimed to investigate whether H2 could modulate lipopolysaccharide (LPS)-stimulated dysfunction of the intestinal barrier and whether RhoA-mDia1 signaling is involved. Caco-2 cells were exposed to different concentrations of LPS (1 μg/mL-1 mg/mL). The permeability of the intestinal barrier was evaluated by transepithelial resistance (TER) and fluorescein-isothiocyanate-dextran flux. Expression and distribution of occludin and E-cadherin were analyzed by Western blot and immunofluorescence. RhoA activity was measured by G-Lisa assay, and mDia1 expression was assessed by Western blot. LPS (100 μg/mL) decreased TER and increased fluorescein-isothiocyanate-dextran flux, which were alleviated by H2-rich medium. Also, H2 down-regulated LPS-induced oxidative stress. Moreover, H2 improved the down-regulated expression and redistribution of occludin and E-cadherin caused by LPS. Additionally, H2 alleviated LPS-caused RhoA activation, and the beneficial effects of H2 on barrier were counteracted by RhoA agonist CN03. Rho inhibitor C3 exoenzyme mitigated LPS-induced barrier breakdown. Furthermore, H2-rich medium increased mDia1 expression, and mDia1 knockdown abolished protections of H2 on barrier permeability. mDia1 knockdown eliminated H2-induced benefits for occludin and E-cadherin. These findings suggest that H2 improves LPS-induced hyperpermeability of the intestinal barrier and disruptions of TJ and AJ by moderating RhoA-mDia1 signaling.", "conclusion": "mDia1 knockdown eliminated H2-induced benefits for occludin and E-cadherin. These findings suggest that H2 improves LPS-induced hyperpermeability of the intestinal barrier and disruptions of TJ and AJ by moderating RhoA-mDia1 signaling." }, { "pmid": "26012504", "year": 2016, "title": "Antioxidants and K+ channel agonists versus hydrogen therapy during ex vivo lung perfusion†.", "title_en": null, "title_de": "Antioxidantien und K⁺-Kanal-Agonisten versus Wasserstofftherapie während der Ex-vivo-Lungenperfusion", "journal": "European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery", "authors": "Mohamed", "author_search": "mohamed mohamed", "doi": "10.1093/ejcts/ezv192", "doi_url": "https://doi.org/10.1093/ejcts/ezv192", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/26012504/", "url": "https://h2medicine.org/studies/study-mohamed-2016-antioxidants-channel-agonists-versus/", "methods": [ "unspecified" ], "indications": [ "respiratory", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2016 · Mohamed — Antioxidants and K⁺ Channel Agonists versus Hydrogen Therapy during Ex Vivo Lung Perfusion", "summary": "This study compared different protective strategies — antioxidants, potassium channel agonists, and hydrogen therapy — applied during ex-vivo lung perfusion (EVLP), a technique used to preserve and assess donor lungs before transplantation. The study was conducted in an animal (non-human) system; the abstract is not publicly available in this record. (European Journal of Cardio-Thoracic Surgery, 2016.)", "assessment": "This is a preclinical ex-vivo animal lung study — not a human transplant trial. The abstract is absent from this database record, making a full scientific assessment impossible here. The comparison of hydrogen therapy against alternative protective strategies in the EVLP context is clinically relevant as a research question, but results cannot be evaluated without the full text. No conclusions about H₂'s clinical use in lung transplantation can be drawn from this record. The full paper is accessible via DOI 10.1093/ejcts/ezv192.", "abstract": null, "conclusion": null }, { "pmid": "25671669", "year": 2016, "title": "Multi-drug resistance profile of PR20 HIV-1 protease is attributed to distorted conformational and drug binding landscape: molecular dynamics insights.", "title_en": null, "title_de": "Das Multiresistenzprofil der PR20-HIV-1-Protease wird einer verzerrten Konformations- und Wirkstoffbindungslandschaft zugeschrieben: Erkenntnisse aus der Molekulardynamik", "journal": "Journal of biomolecular structure & dynamics", "authors": "Chetty et al.", "author_search": "chetty chetty", "doi": "10.1080/07391102.2015.1018326", "doi_url": "https://doi.org/10.1080/07391102.2015.1018326", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/25671669/", "url": "https://h2medicine.org/studies/study-chetty-2016-multi-drug-resistance-profile/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2016 · Chetty — Multi-Drug Resistance Profile of PR20 HIV-1 Protease Is Attributed to Distorted Conformational and Drug Binding Landscape: Molecular Dynamics Insights", "summary": "This computational chemistry study analyzed how 20 mutations in the HIV-1 protease (PR20 variant) distort its structure and reduce drug binding, explaining the high multi-drug resistance of this variant. The study uses molecular dynamics simulation — intramolecular hydrogen bond networks are analyzed as part of the protein structure, not as molecular H₂ therapy. (Journal of Biomolecular Structure & Dynamics, 2016.)", "assessment": "This is a computational structural biology study with no connection to hydrogen medicine or H₂ therapy. „Hydrogen bonds“ in this paper refer to standard chemical interactions within protein structure — a fundamental concept in structural biology with no relationship to molecular hydrogen (H₂) as a bioactive agent. The study is scientifically credible and relevant to HIV drug resistance, but completely outside the scope of H₂ medicine. Its presence in an H₂ database is a keyword-based false positive.", "abstract": "The PR20 HIV-1 protease, a variant with 20 mutations, exhibits high levels of multi-drug resistance; however, to date, there has been no report detailing the impact of these 20 mutations on the conformational and drug binding landscape at a molecular level. In this report, we demonstrate the first account of a comprehensive study designed to elaborate on the impact of these mutations on the dynamic features as well as drug binding and resistance profile, using extensive molecular dynamics analyses. Comparative MD simulations for the wild-type and PR20 HIV proteases, starting from bound and unbound conformations in each case, were performed. Results showed that the apo conformation of the PR20 variant of the HIV protease displayed a tendency to remain in the open conformation for a longer period of time when compared to the wild type. This led to a phenomena in which the inhibitor seated at the active site of PR20 tends to diffuse away from the binding site leading to a significant change in inhibitor-protein association. Calculating the per-residue fluctuation (RMSF) and radius of gyration, further validated these findings. MM/GBSA showed that the occurrence of 20 mutations led to a drop in the calculated binding free energies (ΔGbind) by ~25.17 kcal/mol and ~5 kcal/mol for p2-NC, a natural peptide substrate, and darunavir, respectively, when compared to wild type. Furthermore, the residue interaction network showed a diminished inter-residue hydrogen bond network and changes in inter-residue connections as a result of these mutations. The increased conformational flexibility in PR20 as a result of loss of intra- and inter-molecular hydrogen bond interactions and other prominent binding forces led to a loss of protease grip on ligand. It is interesting to note that the difference in conformational flexibility between PR20 and WT conformations was much higher in the case of substrate-bound conformation as compared to DRV. Thus, developing analogues of DRV by retaining its key pharmacophore features will be the way forward in the search for novel protease inhibitors against multi-drug resistant strains.", "conclusion": "It is interesting to note that the difference in conformational flexibility between PR20 and WT conformations was much higher in the case of substrate-bound conformation as compared to DRV. Thus, developing analogues of DRV by retaining its key pharmacophore features will be the way forward in the search for novel protease inhibitors against multi-drug resistant strains." }, { "pmid": "26571560", "year": 2015, "title": "[Initiation, development and potential of hydrogen medicine: Toward therapeutic and preventive applications of molecular hydrogen against a variety of diseases].", "title_en": null, "title_de": "Anfänge, Entwicklung und Potenzial der Wasserstoffmedizin: Auf dem Weg zu therapeutischen und präventiven Anwendungen von molekularem Wasserstoff gegen eine Vielzahl von Erkrankungen", "journal": "Seikagaku. The Journal of Japanese Biochemical Society", "authors": "Ohta", "author_search": "ohta ohta", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/26571560/", "url": "https://h2medicine.org/studies/study-ohta-2015-initiation-development-medicine-toward/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2015 · Ohta — Initiation, Development and Potential of Hydrogen Medicine: Toward Therapeutic and Preventive Applications of Molecular Hydrogen Against a Variety of Diseases", "summary": "This review by Shigeo Ohta — one of the field's founding scientists — traces the history of hydrogen medicine from its 2007 origins, surveys the mechanistic and clinical evidence across multiple disease areas, and outlines future research directions. As a review article, it synthesizes existing literature rather than presenting new experimental data. (Seikagaku / Journal of the Japanese Biochemical Society, 2015.)", "assessment": "This is a narrative review by one of the founders of hydrogen medicine — not a new experimental study. As a review, it summarizes and interprets existing literature; findings should be understood as the author's synthesis and perspective rather than independent new evidence. The abstract is absent from this database record, making complete evaluation here impossible. As a review, it does not constitute direct clinical evidence, but can provide useful orientation within the field. Readers should access the full text via the journal or DOI for complete arguments.", "abstract": null, "conclusion": null }, { "pmid": "26337845", "year": 2015, "title": "Direct Interspecies Electron Transfer in Anaerobic Digestion: A Review.", "title_en": null, "title_de": "Direkter Interspezies-Elektronentransfer in der anaeroben Vergärung: Eine Übersichtsarbeit", "journal": "Advances in biochemical engineering/biotechnology", "authors": "Dubé et al.", "author_search": "dubé dubé", "doi": "10.1007/978-3-319-21993-6_4", "doi_url": "https://doi.org/10.1007/978-3-319-21993-6_4", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/26337845/", "url": "https://h2medicine.org/studies/study-dube-2015-direct-interspecies-electron-transfer/", "methods": [ "unspecified" ], "indications": [ "sports-exercise" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2015 · Dubé — Direct Interspecies Electron Transfer in Anaerobic Digestion: A Review", "summary": "This review covers „direct interspecies electron transfer“ (DIET) — a form of syntrophic metabolism in anaerobic microbial communities where electrons flow directly between cells without being shuttled by molecular hydrogen or formate. While H₂ is mentioned as a comparison point, this paper is about environmental microbiology and biogas production, not biomedical H₂ therapy. (Advances in Biochemical Engineering/Biotechnology, 2015.)", "assessment": "This is an environmental microbiology review with no connection to human health, hydrogen medicine, or therapeutic H₂. „Molecular hydrogen“ in this paper refers to H₂ gas as a fermentation byproduct in anaerobic microbial ecosystems — a completely different context from biomedical H₂ supplementation. Its inclusion in an H₂ medicine database is a keyword-based false positive. No conclusions relevant to H₂ therapy or human health can be drawn from this paper.", "abstract": "Direct interspecies electrons transfer (DIET) is a syntrophic metabolism in which free electrons flow from one cell to another without being shuttled by reduced molecules such as molecular hydrogen or formate. As more and more microorganisms show a capacity for electron exchange, either to export or import them, it becomes obvious that DIET is a syntrophic metabolism that is much more present in nature than previously thought. This article reviews literature related to DIET, specifically in reference to anaerobic digestion. Anaerobic granular sludge, a biofilm, is a specialized microenvironment where syntrophic bacterial and archaeal organisms grow together in close proximity. Exoelectrogenic bacteria degrading organic substrates or intermediates need an electron sink and electrotrophic methanogens represent perfect partners to assimilate those electrons and produce methane. The granule extracellular polymeric substances by making the biofilm matrix more conductive, play a role as electrons carrier in DIET.", "conclusion": "Exoelectrogenic bacteria degrading organic substrates or intermediates need an electron sink and electrotrophic methanogens represent perfect partners to assimilate those electrons and produce methane. The granule extracellular polymeric substances by making the biofilm matrix more conductive, play a role as electrons carrier in DIET." }, { "pmid": "25958185", "year": 2015, "title": "Chemical communication in the gut: Effects of microbiota-generated metabolites on gastrointestinal bacterial pathogens.", "title_en": null, "title_de": "Chemische Kommunikation im Darm: Wirkungen von mikrobiota-erzeugten Metaboliten auf gastrointestinale bakterielle Pathogene.", "journal": "Anaerobe", "authors": "Vogt et al.", "author_search": "vogt vogt", "doi": "10.1016/j.anaerobe.2015.05.002", "doi_url": "https://doi.org/10.1016/j.anaerobe.2015.05.002", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/25958185/", "url": "https://h2medicine.org/studies/study-vogt-2015-chemical-communication-gut-microbiota/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2015 · Vogt et al. — Chemical communication in the gut: Effects of microbiota-generated metabolites on gastrointestinal bacterial pathogens.", "summary": "The gut microbiota does not merely occupy space — it actively shapes the chemical environment of the intestine through metabolites that can inhibit or promote bacterial pathogens. This review covers key molecules involved, including short-chain fatty acids, bile acids, and molecular hydrogen (H₂), and how they collectively determine the outcome of gut infections. (Anaerobe, 2015.)", "assessment": "This is a narrative review of the scientific literature — not a clinical or experimental study on hydrogen therapy. Molecular hydrogen appears as one metabolite among several, discussed in the context of gut microbial ecology. The review is informative for understanding H₂'s natural role in the intestinal environment, but it provides no direct evidence for therapeutic hydrogen use in humans. The breadth of the review is its strength; the absence of new experimental data is its limitation. Most relevant for researchers interested in the intersection of microbiome science and H₂ biology.", "abstract": "Gastrointestinal pathogens must overcome many obstacles in order to successfully colonize a host, not the least of which is the presence of the gut microbiota, the trillions of commensal microorganisms inhabiting mammals' digestive tracts, and their products. It is well established that a healthy gut microbiota provides its host with protection from numerous pathogens, including Salmonella species, Clostridium difficile, diarrheagenic Escherichia coli, and Vibrio cholerae. Conversely, pathogenic bacteria have evolved mechanisms to establish an infection and thrive in the face of fierce competition from the microbiota for space and nutrients. Here, we review the evidence that gut microbiota-generated metabolites play a key role in determining the outcome of infection by bacterial pathogens. By consuming and transforming dietary and host-produced metabolites, as well as secreting primary and secondary metabolites of their own, the microbiota define the chemical environment of the gut and often determine specific host responses. Although most gut microbiota-produced metabolites are currently uncharacterized, several well-studied molecules made or modified by the microbiota are known to affect the growth and virulence of pathogens, including short-chain fatty acids, succinate, mucin O-glycans, molecular hydrogen, secondary bile acids, and the AI-2 quorum sensing autoinducer. We also discuss challenges and possible approaches to further study of the chemical interplay between microbiota and gastrointestinal pathogens.", "conclusion": "Although most gut microbiota-produced metabolites are currently uncharacterized, several well-studied molecules made or modified by the microbiota are known to affect the growth and virulence of pathogens, including short-chain fatty acids, succinate, mucin O-glycans, molecular hydrogen, secondary bile acids, and the AI-2 quorum sensing autoinducer. We also discuss challenges and possible approach" }, { "pmid": "25936365", "year": 2015, "title": "Molecular hydrogen: An inert gas turns clinically effective.", "title_en": null, "title_de": "Molekularer Wasserstoff: Ein inertes Gas wird klinisch wirksam.", "journal": "Annals of medicine", "authors": "Ostojic", "author_search": "ostojic ostojic", "doi": "10.3109/07853890.2015.1034765", "doi_url": "https://doi.org/10.3109/07853890.2015.1034765", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/25936365/", "url": "https://h2medicine.org/studies/study-ostojic-2015-inert-turns-clinically-effective/", "methods": [ "unspecified" ], "indications": [ "cancer", "immune-system" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2015 · Ostojic — Molecular hydrogen: An inert gas turns clinically effective.", "summary": "For decades considered biologically inert, molecular hydrogen (H₂) has in recent years accumulated clinical evidence — from metabolic diseases to chronic inflammation and cancer. This review by Ostojic summarizes available clinical trial data on H₂ and outlines practical considerations such as dosage, administration routes, and safety. (Annals of Medicine, 2015.)", "assessment": "This is a literature review, not a primary clinical study. Its value lies in aggregating early clinical signals across diverse disease areas rather than in original data. The honest picture it paints: H₂ shows promising signals in metabolic and inflammatory conditions, but dosage guidance and long-term safety data are explicitly insufficient at the time of writing. Practitioners should treat this as a synthesis of early-phase evidence, not as established treatment protocol. The single-author narrative format also means the selection and weighting of studies reflects one researcher's perspective.", "abstract": "Molecular hydrogen (H2) appeared as an experimental agent in biomedicine approximately 40 years ago, yet the past 5 years seem to confirm its medicinal value in the clinical environment. H2 improves clinical end-points and surrogate markers in several clinical trials, from metabolic diseases to chronic systemic inflammatory disorders to cancer. However, less information is available concerning its medicinal properties, such as dosage and administration, or adverse reactions and use in specific populations. The present paper overviews the clinical relevance of molecular hydrogen, and summarizes data from clinical trials on this innovative medical agent. Clinical profiles of H2 provide evidence-based direction for practical application and future research on molecular hydrogen for the wider health care community.", "conclusion": "The present paper overviews the clinical relevance of molecular hydrogen, and summarizes data from clinical trials on this innovative medical agent. Clinical profiles of H2 provide evidence-based direction for practical application and future research on molecular hydrogen for the wider health care community." }, { "pmid": "25747486", "year": 2015, "title": "Molecular hydrogen as a novel antioxidant: overview of the advantages of hydrogen for medical applications.", "title_en": null, "title_de": "Molekularer Wasserstoff als neuartiges Antioxidans: Überblick über die Vorteile von Wasserstoff für medizinische Anwendungen.", "journal": "Methods in enzymology", "authors": "Ohta", "author_search": "ohta ohta", "doi": "10.1016/bs.mie.2014.11.038", "doi_url": "https://doi.org/10.1016/bs.mie.2014.11.038", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/25747486/", "url": "https://h2medicine.org/studies/study-ohta-2015-antioxidant-overview-advantages-medical/", "methods": [ "inhalation", "saline-iv", "bath-topical", "drinking-hrw" ], "indications": [ "eye", "immune-system", "allergy", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2015 · Ohta — Molecular hydrogen as a novel antioxidant: overview of the advantages of hydrogen for medical applications.", "summary": "Molecular hydrogen (H₂) is a mild, selective antioxidant that neutralizes the most damaging reactive oxygen species without disrupting normal cellular redox signaling — a key advantage over broad-spectrum antioxidants. This comprehensive overview by Ohta covers administration methods, biological mechanisms, and the expanding evidence from animal models and clinical studies. (Methods in Enzymology, 2015.)", "assessment": "This is a key review from one of the field's founding researchers, offering a clear mechanistic framework for H₂ as an antioxidant. It is most valuable as a conceptual and methodological reference — cataloguing delivery routes and biological mechanisms. As of 2015, the evidence base was still predominantly animal models and early-phase clinical studies, not large randomized trials. No clinical conclusions should be drawn directly from this review for human therapeutic use. The author's honest acknowledgment that H₂ does not fit the traditional drug paradigm is scientifically important and should not be misread as marketing.", "abstract": "Molecular hydrogen (H2) was believed to be inert and nonfunctional in mammalian cells. We overturned this concept by demonstrating that H2 reacts with highly reactive oxidants such as hydroxyl radical ((•)OH) and peroxynitrite (ONOO(-)) inside cells. H2 has several advantages exhibiting marked effects for medical applications: it is mild enough neither to disturb metabolic redox reactions nor to affect signaling by reactive oxygen species. Therefore, it should have no or little adverse effects. H2 can be monitored with an H2-specific electrode or by gas chromatography. H2 rapidly diffuses into tissues and cells to exhibit efficient effects. Thus, we proposed the potential of H2 for preventive and therapeutic applications. There are several methods to ingest or consume H2: inhaling H2 gas, drinking H2-dissolved water (H2-water), injecting H2-dissolved saline (H2-saline), taking an H2 bath, or dropping H2-saline onto the eyes. Recent publications revealed that, in addition to the direct neutralization of highly reactive oxidants, H2 indirectly reduces oxidative stress by regulating the expression of various genes. Moreover, by regulating gene expression, H2 functions as an anti-inflammatory, antiallergic, and antiapoptotic molecule, and stimulates energy metabolism. In addition to growing evidence obtained by model animal experiments, extensive clinical examinations were performed or are under way. Since most drugs specifically act on their specific targets, H2 seems to differ from conventional pharmaceutical drugs. Owing to its great efficacy and lack of adverse effects, H2 has potential for clinical applications for many diseases.", "conclusion": "Since most drugs specifically act on their specific targets, H2 seems to differ from conventional pharmaceutical drugs. Owing to its great efficacy and lack of adverse effects, H2 has potential for clinical applications for many diseases." }, { "pmid": "25720951", "year": 2015, "title": "Targeting molecular hydrogen to mitochondria: barriers and gateways.", "title_en": null, "title_de": "Gezielte Ausrichtung von molekularem Wasserstoff an Mitochondrien: Barrieren und Zugangswege.", "journal": "Pharmacological research", "authors": "Ostojic", "author_search": "ostojic ostojic", "doi": "10.1016/j.phrs.2015.02.004", "doi_url": "https://doi.org/10.1016/j.phrs.2015.02.004", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/25720951/", "url": "https://h2medicine.org/studies/study-ostojic-2015-targeting-mitochondria-barriers-gateways/", "methods": [ "unspecified" ], "indications": [ "liver", "sports-exercise" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2015 · Ostojic — Targeting molecular hydrogen to mitochondria: barriers and gateways.", "summary": "Mitochondria are a key target for hydrogen therapy, but the double-membrane structure and high membrane potential of these organelles create specific barriers to H₂ delivery that are not yet well understood. This perspective paper by Ostojic examines both the obstacles and potential advantages of getting H₂ into mitochondria. (Pharmacological Research, 2015.)", "assessment": "This is a theoretical perspective piece — it poses hypotheses about mitochondrial H₂ pharmacokinetics but does not test them. No animal or human data is presented. Its value is in framing an important unsolved question in H₂ biology: do mitochondria receive meaningful H₂ concentrations, and how does membrane potential influence this? No practical conclusions for therapeutic use can be drawn from this paper alone. It is useful reading for researchers designing mechanistic or pharmacokinetic studies.", "abstract": "Although the administration of molecular hydrogen (H2, dihydrogen) has been recognized as an effective innovative therapeutic procedure in biomedicine, H2 cellular kinetics and utilization seems to be less understood. In particular, mitochondrial barriers might impact on H2 use in mitochondria-related diseases and conditions. Double-membrane organization of mitochondria and large membrane potential are important elements of mitochondrial stability that control the transport of the molecule into and out of the organelle. In this perspective paper, we advanced possible obstacles and advantages for H2 delivery to mitochondria.", "conclusion": "Double-membrane organization of mitochondria and large membrane potential are important elements of mitochondrial stability that control the transport of the molecule into and out of the organelle. In this perspective paper, we advanced possible obstacles and advantages for H2 delivery to mitochondria." }, { "pmid": "25525953", "year": 2015, "title": "Molecular hydrogen in sports medicine: new therapeutic perspectives.", "title_en": null, "title_de": "Molekularer Wasserstoff in der Sportmedizin: neue therapeutische Perspektiven.", "journal": "International journal of sports medicine", "authors": "Ostojic", "author_search": "ostojic ostojic", "doi": "10.1055/s-0034-1395509", "doi_url": "https://doi.org/10.1055/s-0034-1395509", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/25525953/", "url": "https://h2medicine.org/studies/study-ostojic-2015-sports-medicine-therapeutic-perspectives/", "methods": [ "unspecified" ], "indications": [ "diabetes", "sports-exercise", "neurology", "joints-rheumatology", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2015 · Ostojic — Molecular hydrogen in sports medicine: new therapeutic perspectives.", "summary": "Molecular hydrogen (H₂) may offer a novel approach for addressing exercise-induced oxidative stress and sports injuries, with potential to also improve exercise performance. This review summarizes clinical and research evidence on H₂ across oxidative stress-related conditions and frames its specific relevance for sports medicine. (International Journal of Sports Medicine, 2015.)", "assessment": "A narrative review making the case for H₂'s relevance in sports medicine by synthesizing evidence from adjacent disease areas. The argument is plausible — exercise-induced oxidative stress is a well-established phenomenon — but the direct sports-specific clinical evidence at the time of writing was limited. The proposed performance enhancement angle is speculative and would require dedicated randomized trials for validation. Readers interested in the mechanistic rationale will find value here; those seeking definitive performance data should look for subsequent controlled studies.", "abstract": "In the past 2 decades, molecular hydrogen emerged as a novel therapeutic agent, with antioxidant, anti-inflammatory and anti-apoptotic effects demonstrated in plethora of animal disease models and human studies. Beneficial effects of molecular hydrogen in clinical environment are observed especially in oxidative stress-mediated diseases, such as diabetes mellitus, brain stem infarction, rheumatoid arthritis, or neurodegenerative diseases. A number of more recent studies have reported that molecular hydrogen affects cell signal transduction and acts as an alkalizing agent, with these newly identified mechanisms of action having the potential to widen its application in clinical medicine even further. In particular, hydrogen therapy may be an effective and specific innovative treatment for exercise-induced oxidative stress and sports injury, with potential for the improvement of exercise performance. This review will summarize recent research findings regarding the clinical aspects of molecular hydrogen use, emphasizing its application in the field of sports medicine.", "conclusion": "In particular, hydrogen therapy may be an effective and specific innovative treatment for exercise-induced oxidative stress and sports injury, with potential for the improvement of exercise performance. This review will summarize recent research findings regarding the clinical aspects of molecular hydrogen use, emphasizing its application in the field of sports medicine." }, { "pmid": "25413928", "year": 2015, "title": "Radiation occupational health interventions offered to radiation workers in response to the complex catastrophic disaster at the Fukushima Daiichi Nuclear Power Plant.", "title_en": null, "title_de": "Strahlenschutz-arbeitsmedizinische Maßnahmen für Strahlenarbeiter als Reaktion auf die komplexe katastrophale Havarie im Kernkraftwerk Fukushima Daiichi.", "journal": "Journal of radiation research", "authors": "Shimura et al.", "author_search": "shimura shimura", "doi": "10.1093/jrr/rru110", "doi_url": "https://doi.org/10.1093/jrr/rru110", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/25413928/", "url": "https://h2medicine.org/studies/study-shimura-2015-radiation-occupational-health-interventions/", "methods": [ "inhalation" ], "indications": [ "cancer", "skin-aging" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2015 · Shimura et al. — Radiation occupational health interventions offered to radiation workers in response to the complex catastrophic disaster at the Fukushima Daiichi Nuclear Power Plant.", "summary": "Following the 2011 Fukushima nuclear disaster, a comprehensive set of occupational health measures protected emergency workers from radiation overexposure — fewer than 1% received doses above 100 mSv, and no deaths from radiation were reported. This review documents the interventions used, including dosimetry improvements, iodine administration, and health tracking systems. (Journal of Radiation Research, 2015.)", "assessment": "This is a review of occupational health and radiation protection interventions following the Fukushima disaster. It is not a study on molecular hydrogen as a therapeutic or medical agent. Hydrogen appears in this paper only as the explosive gas that caused structural damage at the plant. The paper provides no evidence for or against hydrogen medicine. It is included here for completeness of the source dataset; its relevance to H₂ health science is indirect at best.", "abstract": "The Fukushima Daiichi Nuclear Power Plant (NPP) 1 was severely damaged from the chain reaction of the Great East Japan Earthquake and Tsunami on 11 March 2011, and the consequent meltdown and hydrogen gas explosions. This resulted in the worst nuclear accident since the Chernobyl accident of 1986. Just as in the case of Chernobyl, emergency workers were recruited to conduct a wide range of tasks, including disaster response, rescuing activities, NPP containment, and radiation decontamination. This paper describes the types and efficacy of the various occupational health interventions introduced to the Fukushima NPP radiation workers. Such interventions were implemented in order to prevent unnecessary radiation overexposure and associated adverse health effects and work injuries. Less than 1% of all emergency workers were exposed to external radiation of >100 mSv, and to date no deaths or health adversities from radiation have been reported for those workers. Several occupational health interventions were conducted, including setting of new regulatory exposure limits, improving workers' radiation dosimetry, administration of stable iodine, running an occupational health tracking system, and improving occupational medicine and preventative care. Those interventions were not only vital for preventing unnecessary radiation, but also for managing other general health issues such as mental health, heat illness and infectious diseases. Long-term administration of the aforementioned occupational health interventions is essential to ensure the ongoing support and care for these workers, who were put under one of the most severe occupational health risk conditions ever encountered.", "conclusion": "Those interventions were not only vital for preventing unnecessary radiation, but also for managing other general health issues such as mental health, heat illness and infectious diseases. Long-term administration of the aforementioned occupational health interventions is essential to ensure the ongoing support and care for these workers, who were put under one of the most severe occupational heal" }, { "pmid": "24754449", "year": 2015, "title": "Advances in the biotechnology of hydrogen production with the microalga Chlamydomonas reinhardtii.", "title_en": null, "title_de": "Fortschritte in der Biotechnologie der Wasserstoffproduktion mit der Mikroalge Chlamydomonas reinhardtii.", "journal": "Critical reviews in biotechnology", "authors": "Torzillo et al.", "author_search": "torzillo torzillo", "doi": "10.3109/07388551.2014.900734", "doi_url": "https://doi.org/10.3109/07388551.2014.900734", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/24754449/", "url": "https://h2medicine.org/studies/study-torzillo-2015-advances-biotechnology-production-microalga/", "methods": [ "inhalation" ], "indications": [ "other" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2015 · Torzillo et al. — Advances in the biotechnology of hydrogen production with the microalga Chlamydomonas reinhardtii.", "summary": "The green microalga Chlamydomonas reinhardtii can produce hydrogen gas from sunlight and water — a clean energy prospect, but one still far from industrial viability. This review covers a decade of progress in algal biohydrogen production following the key discovery of sulfur-deprivation as a trigger for sustained H₂ output. (Critical Reviews in Biotechnology, 2015.)", "assessment": "This review has no direct relevance to molecular hydrogen as a medical or therapeutic agent. It is energy biotechnology research focused on green H₂ fuel production via photosynthetic microalgae. Its scientific quality is not in question — but readers looking for evidence on H₂ health effects will find nothing applicable here. The review is thorough about both the promise and the significant remaining barriers to industrial-scale algal hydrogen production.", "abstract": "Biological hydrogen production is being evaluated for use as a fuel, since it is a promising substitute for carbonaceous fuels owing to its high conversion efficiency and high specific energy content. The basic advantages of biological hydrogen production over other \"green\" energy sources are that it does not compete for agricultural land use, and it does not pollute, as water is the only by-product of the combustion. These characteristics make hydrogen a suitable fuel for the future. Among several biotechnological approaches, photobiological hydrogen production carried out by green microalgae has been intensively investigated in recent years. A select group of photosynthetic organisms has evolved the ability to harness light energy to drive hydrogen gas production from water. Of these, the microalga Chlamydomonas reinhardtii is considered one of the most promising eukaryotic H2 producers. In this model microorganism, light energy, H2O and H2 are linked by two excellent catalysts, the photosystem 2 (PSII) and the [FeFe]-hydrogenase, in a pathway usually referred to as direct biophotolysis. This review summarizes the main advances made over the past decade as an outcome of the discovery of the sulfur-deprivation process. Both the scientific and technical barriers that need to be overcome before H2 photoproduction can be scaled up to an industrial level are examined. Actual and theoretical limits of the efficiency of the process are also discussed. Particular emphasis is placed on algal biohydrogen production outdoors, and guidelines for an optimal photobioreactor design are suggested.", "conclusion": "Actual and theoretical limits of the efficiency of the process are also discussed. Particular emphasis is placed on algal biohydrogen production outdoors, and guidelines for an optimal photobioreactor design are suggested." }, { "pmid": "26596710", "year": 2015, "title": "Discovery of novel quinoline-based mTOR inhibitors via introducing intra-molecular hydrogen bonding scaffold (iMHBS): The design, synthesis and biological evaluation.", "title_en": null, "title_de": "Entdeckung neuartiger chinolinbasierter mTOR-Inhibitoren durch Einführung eines intramolekularen Wasserstoffbrücken-Gerüsts (iMHBS): Design, Synthese und biologische Bewertung.", "journal": "Bioorganic & medicinal chemistry", "authors": "Ma et al.", "author_search": "ma ma", "doi": "10.1016/j.bmc.2015.11.003", "doi_url": "https://doi.org/10.1016/j.bmc.2015.11.003", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/26596710/", "url": "https://h2medicine.org/studies/study-ma-2015-discovery-quinoline-mtor-inhibitors/", "methods": [ "unspecified" ], "indications": [ "liver" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2015 · Ma et al. — Discovery of novel quinoline-based mTOR inhibitors via introducing intra-molecular hydrogen bonding scaffold (iMHBS): The design, synthesis and biological evaluation.", "summary": "Researchers designed and synthesized a series of quinoline compounds that use intramolecular hydrogen bonding to inhibit the mTOR enzyme — a key cancer growth regulator — with several candidates showing potent activity against cancer cell lines. This is a medicinal chemistry in-vitro study; it does not investigate molecular hydrogen as a medical gas. (Bioorganic and Medicinal Chemistry, 2015.)", "assessment": "This is an in-vitro medicinal chemistry study about intramolecular hydrogen bonding in cancer drug design — not a study on molecular hydrogen (H₂) as a therapeutic agent. The word „hydrogen“ here refers to hydrogen atoms within chemical bonds, a different concept entirely. The results are promising at the cell culture level but require extensive animal and eventually human testing before any clinical conclusions can be drawn. This study provides no evidence for or against hydrogen gas therapy.", "abstract": "A series of quinoline derivatives featuring the novelty of introducing intra-molecular hydrogen bonding scaffold (iMHBS) were designed, synthesized and biologically evaluated for their mTOR inhibitory activity, as well as anti-proliferative efficacies against HCT-116, PC-3 and MCF-7 cell lines. As a result, six compounds exhibited significant inhibition against mTOR with IC50 values below 35nM. Compound 15a, the most potent mTOR inhibitor reported herein (IC50=14nM), also displayed the most favorable cellular activities, with the IC50 values of 0.46, 0.61 and 0.24μM against HCT-116, PC-3 and MCF-7, respectively. Besides, several compounds in this series were identified to be selective over class I PI3Ks. Further western blot analysis of 16b, a representative compound in this series, highlighted their advantage in surmounting the S6K/IRS1/PI3K negative feedback loop upon dual inhibition of mTORC1 and mTORC2. In addition to the remarkable activity, 15a demonstrated acceptable stability in simulated gastric fluid (SGF), simulated intestinal fluid (SIF) and liver microsome, thereby being valuable for extensive in vivo investigation.", "conclusion": "Further western blot analysis of 16b, a representative compound in this series, highlighted their advantage in surmounting the S6K/IRS1/PI3K negative feedback loop upon dual inhibition of mTORC1 and mTORC2. In addition to the remarkable activity, 15a demonstrated acceptable stability in simulated gastric fluid (SGF), simulated intestinal fluid (SIF) and liver microsome, thereby being valuable for " }, { "pmid": "26271894", "year": 2015, "title": "Hydrogen-rich water attenuates amyloid β-induced cytotoxicity through upregulation of Sirt1-FoxO3a by stimulation of AMP-activated protein kinase in SK-N-MC cells.", "title_en": null, "title_de": "Wasserstoffreiches Wasser mildert die durch Amyloid-β induzierte Zytotoxizität durch Hochregulation von Sirt1-FoxO3a über die Stimulation der AMP-aktivierten Proteinkinase in SK-N-MC-Zellen.", "journal": "Chemico-biological interactions", "authors": "Lin et al.", "author_search": "lin lin", "doi": "10.1016/j.cbi.2015.07.013", "doi_url": "https://doi.org/10.1016/j.cbi.2015.07.013", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/26271894/", "url": "https://h2medicine.org/studies/study-lin-2015-attenuates-amyloid-induced-cytotoxicity/", "methods": [ "drinking-hrw" ], "indications": [ "neurology", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2015 · Lin et al. — Hydrogen-rich water attenuates amyloid β-induced cytotoxicity through upregulation of Sirt1-FoxO3a by stimulation of AMP-activated protein kinase in SK-N-MC cells.", "summary": "In neuronal cell culture, hydrogen-rich water (HRW) protected cells against amyloid beta (Aβ) — the peptide linked to Alzheimer's disease — both by directly neutralizing reactive oxygen species and by activating a protective cell-signaling cascade (AMPK → Sirt1 → FoxO3a). This is an in-vitro study; results have not been confirmed in animals or humans. (Chemico-Biological Interactions, 2015.)", "assessment": "A mechanistically interesting in-vitro study that identifies the AMPK–Sirt1–FoxO3a pathway as a potential mediator of HRW's neuroprotective effects against Aβ toxicity. These are cell culture findings only — they cannot be extrapolated to Alzheimer's disease in humans. The neuroblastoma cell model is a useful but simplified system; the complexity of Alzheimer's pathology in vivo involves many factors not captured in this setup. The study provides a hypothesis and molecular targets for future preclinical and eventually clinical investigation — nothing more at this stage.", "abstract": "Amyloid β (Aβ) peptides are identified in cause of neurodegenerative diseases such as Alzheimer's disease (AD). Previous evidence suggests Aβ-induced neurotoxicity is linked to the stimulation of reactive oxygen species (ROS) production. The accumulation of Aβ-induced ROS leads to increased mitochondrial dysfunction and triggers apoptotic cell death. This suggests antioxidant therapies may be beneficial for preventing ROS-related diseases such as AD. Recently, hydrogen-rich water (HRW) has been proven effective in treating oxidative stress-induced disorders because of its ROS-scavenging abilities. However, the precise molecular mechanisms whereby HRW prevents neuronal death are still unclear. In the present study, we evaluated the putative pathways by which HRW protects against Aβ-induced cytotoxicity. Our results indicated that HRW directly counteracts oxidative damage by neutralizing excessive ROS, leading to the alleviation of Aβ-induced cell death. In addition, HRW also stimulated AMP-activated protein kinase (AMPK) in a sirtuin 1 (Sirt1)-dependent pathway, which upregulates forkhead box protein O3a (FoxO3a) downstream antioxidant response and diminishes Aβ-induced mitochondrial potential loss and oxidative stress. Taken together, our findings suggest that HRW may have potential therapeutic value to inhibit Aβ-induced neurotoxicity.", "conclusion": "In addition, HRW also stimulated AMP-activated protein kinase (AMPK) in a sirtuin 1 (Sirt1)-dependent pathway, which upregulates forkhead box protein O3a (FoxO3a) downstream antioxidant response and diminishes Aβ-induced mitochondrial potential loss and oxidative stress. Taken together, our findings suggest that HRW may have potential therapeutic value to inhibit Aβ-induced neurotoxicity." }, { "pmid": "26253656", "year": 2015, "title": "Molecular hydrogen protects mice against polymicrobial sepsis by ameliorating endothelial dysfunction via an Nrf2/HO-1 signaling pathway.", "title_en": null, "title_de": "Molekularer Wasserstoff schützt Mäuse vor polymikrobieller Sepsis durch Milderung der Endotheldysfunktion über einen Nrf2/HO-1-Signalweg.", "journal": "International immunopharmacology", "authors": "Chen et al.", "author_search": "chen chen", "doi": "10.1016/j.intimp.2015.07.034", "doi_url": "https://doi.org/10.1016/j.intimp.2015.07.034", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/26253656/", "url": "https://h2medicine.org/studies/study-chen-2015-protects-mice-against-polymicrobial/", "methods": [ "unspecified" ], "indications": [ "cardiovascular", "cancer", "respiratory", "immune-system" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2015 · Chen et al. — Molecular hydrogen protects mice against polymicrobial sepsis by ameliorating endothelial dysfunction via an Nrf2/HO-1 signaling pathway.", "summary": "In a mouse sepsis model, molecular hydrogen suppressed the inflammatory cascade and endothelial injury — both in cell culture and in live animals — by activating the Nrf2/HO-1 antioxidant pathway. This is a preclinical study combining in-vitro and animal experiments; results cannot be directly applied to human sepsis treatment. (International Immunopharmacology, 2015.)", "assessment": "A well-designed preclinical study with both in-vitro and animal components, providing mechanistic evidence that H₂ can reduce sepsis-associated endothelial injury via the Nrf2/HO-1 pathway. The use of Nrf2 knockout mice to confirm the pathway is a strength. However, this is a mouse study — results cannot be directly translated to human sepsis management. The CLP sepsis model has repeatedly shown poor translation to human outcomes in drug development. The findings are hypothesis-generating for future clinical investigation, not a basis for treatment decisions.", "abstract": "Endothelial injury is a primary cause of sepsis and sepsis-induced organ damage. Heme oxygenase-1 (HO-1) plays an essential role in endothelial cellular defenses against inflammation by activating nuclear factor E2-related factor-2 (Nrf2). We found that molecular hydrogen (H2) exerts an anti-inflammatory effect. Here, we hypothesized that H2 attenuates endothelial injury and inflammation via an Nrf2-mediated HO-1 pathway during sepsis. First, we detected the effects of H2 on cell viability and cell apoptosis in human umbilical vein endothelial cells (HUVECs) stimulated by LPS. Then, we measured cell adhesion molecules and inflammatory factors in HUVECs stimulated by LPS and in a cecal ligation and puncture (CLP)-induced sepsis mouse model. Next, the role of Nrf2/HO-1 was investigated in activated HUVECs, as well as in wild-type and Nrf(-/-) mice with sepsis. We found that both 0.3 mmol/L and 0.6 mmol/L (i.e., saturated) H2-rich media improved cell viability and cell apoptosis in LPS-activated HUVECs and that 0.6mmol/L (i.e., saturated) H2-rich medium exerted an optimal effect. H2 could suppress the release of cell adhesion molecules, such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1), and pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β and high-mobility group box 1 protein (HMGB1). Furthermore, H2 could elevate anti-inflammatory cytokine IL-10 levels in LPS-stimulated HUVECs and in lung tissue from CLP mice. H2 enhanced HO-1 expression and activity in vitro and in vivo. HO-1 inhibition reversed the regulatory effects of H2 on cell adhesion molecules and inflammatory factors. H2 regulated endothelial injury and the inflammatory response via Nrf2-mediated HO-1 levels. These results suggest that H2 could suppress excessive inflammatory responses and endothelial injury via an Nrf2/HO-1 pathway.", "conclusion": "H2 regulated endothelial injury and the inflammatory response via Nrf2-mediated HO-1 levels. These results suggest that H2 could suppress excessive inflammatory responses and endothelial injury via an Nrf2/HO-1 pathway." }, { "pmid": "26125821", "year": 2015, "title": "Protective effects of hydrogen-rich medium on lipopolysaccharide-induced monocytic adhesion and vascular endothelial permeability through regulation of vascular endothelial cadherin.", "title_en": null, "title_de": "Schützende Wirkungen von wasserstoffreichem Medium auf die lipopolysaccharid-induzierte monozytäre Adhäsion und die Permeabilität des Gefäßendothels durch Regulation des vaskulären endothelialen Cadherins.", "journal": "Genetics and molecular research : GMR", "authors": "Yu et al.", "author_search": "yu yu", "doi": "10.4238/2015.june.9.6", "doi_url": "https://doi.org/10.4238/2015.june.9.6", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/26125821/", "url": "https://h2medicine.org/studies/study-yu-2015-protective-medium-lipopolysaccharide-induced/", "methods": [ "unspecified" ], "indications": [ "cardiovascular", "joints-rheumatology" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2015 · Yu et al. — Protective effects of hydrogen-rich medium on lipopolysaccharide-induced monocytic adhesion and vascular endothelial permeability through regulation of vascular endothelial cadherin.", "summary": "In endothelial cell culture, hydrogen-rich medium reduced the inflammation-triggered adhesion of monocytes to vessel walls and preserved the integrity of the endothelial barrier — effects mediated through the adhesion protein VE-cadherin. This is an in-vitro study; these cell culture findings have not been validated in animals or humans. (Genetics and Molecular Research, 2015.)", "assessment": "A focused in-vitro study identifying VE-cadherin regulation as a mechanism by which H₂ may protect vascular endothelium from inflammatory damage. The methodology — combining flow cytometry, ELISA, TEER, Western blot, and immunofluorescence — is multi-faceted and internally consistent. All findings are from cell culture and cannot be directly applied to cardiovascular or inflammatory disease management in humans. The VE-cadherin finding adds a specific, testable molecular target for future in-vivo H₂ research.", "abstract": "We observed the effect of hydrogen-rich medium on lipopolysaccharide (LPS)-induced human umbilical vein endothelial cells (HUVECs), hyaline leukocyte conglutination, and permeability of the endothelium. Endotheliocytes were inoculated on 6-well plates and randomly divided into 4 groups: control, H2, LPS, LPS+H2, H2, and LPS+H2 in saturated hydrogen-rich medium. We applied Wright's stain-ing to observe conglutination of hyaline leukocytes and HUVECs, flow cytometry to determine the content of vascular cell adhesion protein 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1), enzyme-linked immunosorbent assay to measure the E-selectin concentration in the cell liquor, the transendothelial electrical resistance (TEER) to test the permeability of endothelial cells, and Western blot and immunofluorescence to test the expression and distribution of vascular endothelial (VE)-cadherin. Compared with control cells, there was an increase in endothelium-hyaline leukocyte conglutination, a reduction in VCAM-1, ICAM-1, and E-selectin, and the TEER value increased obviously. Compared with LPS, there was an obvious reduction in the conglutination of LPS+H2 cells, a reduction in VCAM-1, ICAM-1, and E-selectin levels, and a reduction in the TEER-resistance value, while the expression of VE-cadherin increased. Fluorescence results showed that, compared with control cells, the VE-cadherin in LPS cells was in-complete at the cell joints. Compared with LPS cells, the VE-cadherin in LPS+H2 cells was even and complete at the cell joints. Liquid rich in hydrogen could reduce LPS-induced production of adhesion molecules and endothelium-hyaline leukocyte conglutination, and influence the expression and distribution of VE-cadherin to regulate the permeability of the endothelium.", "conclusion": "Compared with LPS cells, the VE-cadherin in LPS+H2 cells was even and complete at the cell joints. Liquid rich in hydrogen could reduce LPS-induced production of adhesion molecules and endothelium-hyaline leukocyte conglutination, and influence the expression and distribution of VE-cadherin to regulate the permeability of the endothelium." }, { "pmid": "26117323", "year": 2015, "title": "Molecular hydrogen stabilizes atherosclerotic plaque in low-density lipoprotein receptor-knockout mice.", "title_en": null, "title_de": "Molekularer Wasserstoff stabilisiert atherosklerotische Plaque in Low-Density-Lipoprotein-Rezeptor-Knockout-Mäusen.", "journal": "Free radical biology & medicine", "authors": "Song et al.", "author_search": "song song", "doi": "10.1016/j.freeradbiomed.2015.06.018", "doi_url": "https://doi.org/10.1016/j.freeradbiomed.2015.06.018", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/26117323/", "url": "https://h2medicine.org/studies/study-song-2015-stabilizes-atherosclerotic-plaque-low/", "methods": [ "unspecified" ], "indications": [ "metabolic", "cardiovascular", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2015 · Song et al. — Molecular hydrogen stabilizes atherosclerotic plaque in low-density lipoprotein receptor-knockout mice.", "summary": "In atherosclerosis-prone mice, molecular hydrogen stabilized vulnerable plaque — increasing collagen content, reducing macrophage infiltration, and suppressing the endoplasmic reticulum stress and oxidative damage that drive plaque rupture. This is a preclinical animal study; its relevance to human cardiovascular disease remains to be established in clinical research. (Free Radical Biology and Medicine, 2015.)", "assessment": "A well-executed preclinical study in an established atherosclerosis mouse model, showing plaque-stabilizing effects of H₂ comparable to simvastatin with mechanistic support from both in-vivo and in-vitro experiments. This is animal research — the findings cannot be directly applied to human cardiovascular disease. The LDLR-knockout model has known limitations in translating to human plaque biology. The Nrf2 pathway finding and the comparison with an approved drug (simvastatin) make this a strong hypothesis-generating study warranting clinical follow-up investigation.", "abstract": "Hydrogen (H(2)) attenuates the development of atherosclerosis in mouse models. We aimed to examine the effects of H(2) on atherosclerotic plaque stability. Low-density lipoprotein receptor-knockout (LDLR(-/-)) mice fed an atherogenic diet were dosed daily with H(2) and/or simvastatin. In vitro studies were carried out in an oxidized-LDL (ox-LDL)-stimulated macrophage-derived foam cell model treated with or without H(2). H(2) or simvastatin significantly enhanced plaque stability by increasing levels of collagen, as well as reducing macrophage and lipid levels in plaques. The decreased numbers of dendritic cells and increased numbers of regulatory T cells in plaques further supported the stabilizing effect of H(2) or simvastatin. Moreover, H(2) treatment decreased serum ox-LDL level and apoptosis in plaques with concomitant inhibition of endoplasmic reticulum stress (ERS) and reduction of reactive oxygen species (ROS) accumulation in the aorta. In vitro, like the ERS inhibitor 4-phenylbutyric acid, H(2) inhibited ox-LDL- or tunicamycin (an ERS inducer)-induced ERS response and cell apoptosis. In addition, like the ROS scavenger N-acetylcysteine, H(2) inhibited ox-LDL- or Cu(2+) (an ROS inducer)-induced reduction in cell viability and increase in cellular ROS. Also, H(2) increased Nrf2 (NF-E2-related factor-2, an important factor in antioxidant signaling) activation and Nrf2 small interfering RNA abolished the protective effect of H(2) on ox-LDL-induced cellular ROS production. The inhibitory effects of H(2) on the apoptosis of macrophage-derived foam cells, which take effect by suppressing the activation of the ERS pathway and by activating the Nrf2 antioxidant pathway, might lead to an improvement in atherosclerotic plaque stability.", "conclusion": "Also, H(2) increased Nrf2 (NF-E2-related factor-2, an important factor in antioxidant signaling) activation and Nrf2 small interfering RNA abolished the protective effect of H(2) on ox-LDL-induced cellular ROS production. The inhibitory effects of H(2) on the apoptosis of macrophage-derived foam cells, which take effect by suppressing the activation of the ERS pathway and by activating the Nrf2 an" }, { "pmid": "26077945", "year": 2015, "title": "Effect of T68A/N126Y mutations on the conformational and ligand binding landscape of Coxsackievirus B3 3C protease.", "title_en": null, "title_de": "Wirkung der T68A/N126Y-Mutationen auf die Konformations- und Ligandenbindungslandschaft der Coxsackievirus-B3-3C-Protease.", "journal": "Molecular bioSystems", "authors": "Bhakat", "author_search": "bhakat bhakat", "doi": "10.1039/c5mb00262a", "doi_url": "https://doi.org/10.1039/c5mb00262a", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/26077945/", "url": "https://h2medicine.org/studies/study-bhakat-2015-t68a-n126y-mutations-conformational/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2015 · Bhakat — Effect of T68A/N126Y mutations on the conformational and ligand binding landscape of Coxsackievirus B3 3C protease.", "summary": "Computational modelling reveals how two point mutations in the Coxsackievirus B3 (CVB3) 3C protease weaken the enzyme's grip on its antiviral inhibitor — a structural basis for drug resistance. Molecular dynamics simulations show that the double mutation T68A/N126Y increases conformational flexibility and reduces binding free energy by approximately 3 kcal/mol. This is a purely computational, cell-free study with no animal or human data.", "assessment": "This is a computational in-silico study — no cells, no animals, no humans were involved. Its results cannot be transferred directly to human biology or therapy. The study contributes to structural virology and antiviral drug design, not to molecular hydrogen (H₂) medicine. It appears in an H₂ research database solely because of keyword overlap with „hydrogen bonds,“ which are ubiquitous in biochemistry and unrelated to dissolved molecular H₂. The methodology is sound for its purpose, but the relevance to H₂ therapeutics is nil.", "abstract": "3C protease of Coxsackievirus B3 (CVB3) plays an essential role in the viral replication cycle, and therefore, emerged as an attractive therapeutic target for the treatment of human diseases caused by CVB3 infection. In this study, we report the first account of the molecular impact of the T68A/N126Y double mutant (Mutant(Bound)) using an integrated computational approach. Molecular dynamics simulation and post-dynamics binding free energy, principal component analysis (PCA), hydrogen bond occupancy, SASA, R(g) and RMSF confirm that T68A/N126Y instigated an increased conformational flexibility due to the loss of intra- and inter-molecular hydrogen bond interactions and other prominent binding forces, which led to a decreased protease grip on the ligand (3CPI). The double mutations triggered a distortion orientation of 3CPI in the active site and decreases the binding energy, ΔG(bind) (∼3 kcal mol(-1)), compared to the wild type (Wild(Bound)). The van der Waals and electrostatic energy contributions coming from residues 68 and 126 are lower for Mutant(Bound) when compared with Wild(Bound). In addition, variation in the overall enzyme motion as evident from the PCA, distorted hydrogen bonding network and loss of protein-ligand interactions resulted in a loss of inhibitor efficiency. The comprehensive molecular insight gained from this study should be of great importance in understanding the drug resistance against CVB3 3C protease; also, it will assist in the designing of novel Coxsackievirus B3 inhibitors with high ligand efficacy on resistant strains.", "conclusion": "In addition, variation in the overall enzyme motion as evident from the PCA, distorted hydrogen bonding network and loss of protein-ligand interactions resulted in a loss of inhibitor efficiency. The comprehensive molecular insight gained from this study should be of great importance in understanding the drug resistance against CVB3 3C protease; also, it will assist in the designing of novel Coxsa" }, { "pmid": "26028929", "year": 2015, "title": "Determination of rifaximin treatment period according to lactulose breath test values in nonconstipated irritable bowel syndrome subjects.", "title_en": null, "title_de": "Bestimmung der Rifaximin-Behandlungsdauer anhand von Laktulose-Atemtestwerten bei nicht-obstipierten Reizdarmsyndrom-Probanden.", "journal": "Journal of Korean medical science", "authors": "Bae et al.", "author_search": "bae bae", "doi": "10.3346/jkms.2015.30.6.757", "doi_url": "https://doi.org/10.3346/jkms.2015.30.6.757", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/26028929/", "url": "https://h2medicine.org/studies/study-bae-2015-determination-rifaximin-period-according/", "methods": [], "indications": [ "other" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "breath-test", "headline": "2015 · Bae et al. — Determination of rifaximin treatment period according to lactulose breath test values in nonconstipated irritable bowel syndrome subjects.", "summary": "This retrospective study in 102 IBS patients with confirmed SIBO used lactulose breath test (LBT) H₂ values to determine optimal rifaximin treatment duration (4, 8, or 12 weeks), finding that higher baseline breath H₂ required longer treatment and that symptomatic improvement preceded LBT normalization. (Journal of Korean Medical Science, 2015.)", "assessment": "This is a diagnostic utility study for breath H₂ testing in SIBO/IBS, not a therapeutic H₂ intervention trial. Its inclusion in a H₂ medicine database is valid but requires careful framing: the H₂ here is a biomarker produced by gut bacteria, not an externally administered therapeutic agent. Limitations: retrospective design; single center; n=102 with unequal group sizes; LBT has known sensitivity/specificity limitations for SIBO diagnosis. The clinical finding (individualize rifaximin duration by LBT) has practical value for gastroenterology practice.", "abstract": "Small intestinal bacterial overgrowth (SIBO) can partly explain irritable bowel syndrome (IBS), and rifaximin has been observed to improve abdominal symptoms in nonconstipated IBS patients. However, there are few reports on the association of the rifaximin treatment periods with the results of a lactulose breath test (LBT). Therefore, we performed a retrospective review of patient charts to investigate the relation between the rifaximin treatment periods with LBT results in nonconstipated IBS patients. We also evaluated the time to achieve a symptomatic improvement in the IBS patients as compared to the changes in the LBT. We reviewed the charts for patients who showed IBS symptoms with documented positive results for LBT during their initial visit and who had a follow-up LBT after treatment with rifaximin. The LBT values were compared to the subjects' symptom scores. A total of 102 subjects had a follow-up LBT to assess LBT normalization. The subjects were divided into groups according to treatment periods of 4 weeks (n = 36), 8 weeks (n = 43), and 12 weeks (n = 23). The groups with a longer treatment exhibited an increase in the hydrogen gas value at 90 min and its sum during 90 min at the initial LBT. There were significant differences in hydrogen gas value at 90 min and in its sum during 90 min at the initial LBT between the groups treated for 4 and 12 weeks. The most significant treatment response was observed during the first 4 weeks for all treatment groups. Symptomatic improvement occurred earlier than LBT normalization in the treatment period over 4 weeks. The results indicate that different rifaximin treatment periods are needed in accordance with LBT levels to effectively eradicate SIBO.", "conclusion": "Symptomatic improvement occurred earlier than LBT normalization in the treatment period over 4 weeks. The results indicate that different rifaximin treatment periods are needed in accordance with LBT levels to effectively eradicate SIBO." }, { "pmid": "26011121", "year": 2015, "title": "Atomic Insight into the Altered O6-Methylguanine-DNA Methyltransferase Protein Architecture in Gastric Cancer.", "title_en": null, "title_de": "Atomarer Einblick in die veränderte Proteinarchitektur der O6-Methylguanin-DNA-Methyltransferase bei Magenkrebs.", "journal": "PloS one", "authors": "Chikan et al.", "author_search": "chikan chikan", "doi": "10.1371/journal.pone.0127741", "doi_url": "https://doi.org/10.1371/journal.pone.0127741", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/26011121/", "url": "https://h2medicine.org/studies/study-chikan-2015-atomic-insight-altered-methylguanine/", "methods": [ "unspecified" ], "indications": [ "sports-exercise", "neurology", "cancer" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2015 · Chikan et al. — Atomic Insight into the Altered O6-Methylguanine-DNA Methyltransferase Protein Architecture in Gastric Cancer.", "summary": "A missense mutation at codon 151 of the DNA-repair protein MGMT — found in nearly 40 % of tested gastric-cancer tissue samples — causes major structural disruption of the protein's active site, as shown by molecular dynamics simulation. The mutation (Serine → Isoleucine) destabilises key salt bridges and alters the DNA-binding domain. This is a computational and clinical-sequencing study; no molecular hydrogen (H₂) is involved.", "assessment": "This is a computational in-silico study combined with mutational screening of clinical samples — no interventional experiments were performed. The findings are hypothesis-generating: the identified mutation plausibly impairs MGMT function and could contribute to gastric carcinogenesis, but functional validation in cell or animal models is still needed. The study has no relevance to molecular hydrogen (H₂) therapy or biology; it deals with hydrogen bonds as a standard biochemical concept. It belongs to structural oncology and DNA-repair research.", "abstract": "O6-methylguanine-DNA methyltransferase (MGMT) is one of the major DNA repair protein that counteracts the alkalyting agent-induced DNA damage by replacing O6-methylguanine (mutagenic lesion) back to guanine, eventually suppressing the mismatch errors and double strand crosslinks. Exonic alterations in the form of nucleotide polymorphism may result in altered protein structure that in turn can lead to the loss of function. In the present study, we focused on the population feared for high exposure to alkylating agents owing to their typical and specialized dietary habits. To this end, gastric cancer patients pooled out from the population were selected for the mutational screening of a specific error prone region of MGMT gene. We found that nearly 40% of the studied neoplastic samples harbored missense mutation at codon151 resulting into Serine to Isoleucine variation. This variation resulted in bringing about the structural disorder, subsequently ensuing into a major stoichiometric variance in recognition domain, substrate binding and selectivity loop of the active site of the MGMT protein, as observed under virtual microscope of molecular dynamics simulation (MDS). The atomic insight into MGMT protein by computational approach showed a significant change in the intra molecular hydrogen bond pattern, thus leading to the observed structural anomalies. To further examine the mutational implications on regulatory plugs of MGMT that holds the protein in a DNA-Binding position, a MDS based analysis was carried out on, all known physically interacting amino acids essentially clustered into groups based on their position and function. The results generated by physical-functional clustering of protein indicated that the identified mutation in the vicinity of the active site of MGMT protein causes the local and global destabilization of a protein by either eliminating the stabilizing salt bridges in cluster C3, C4, and C5 or by locally destabilizing the \"protein stabilizing hing\" mapped on C3-C4 cluster, preceding the active site.", "conclusion": "To further examine the mutational implications on regulatory plugs of MGMT that holds the protein in a DNA-Binding position, a MDS based analysis was carried out on, all known physically interacting amino acids essentially clustered into groups based on their position and function. The results generated by physical-functional clustering of protein indicated that the identified mutation in the vici" }, { "pmid": "26009165", "year": 2015, "title": "Michael acceptor in gambogic acid--Its role and application for potent antitumor agents.", "title_en": null, "title_de": "Michael-Akzeptor in Gambogasäure — seine Rolle und Anwendung für potente Antitumor-Wirkstoffe.", "journal": "Bioorganic & medicinal chemistry letters", "authors": "Wang et al.", "author_search": "wang wang", "doi": "10.1016/j.bmcl.2015.04.100", "doi_url": "https://doi.org/10.1016/j.bmcl.2015.04.100", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/26009165/", "url": "https://h2medicine.org/studies/study-wang-2015-michael-acceptor-gambogic-acid/", "methods": [ "unspecified" ], "indications": [ "cancer" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2015 · Wang et al. — Michael acceptor in gambogic acid — Its role and application for potent antitumor agents.", "summary": "Gambogic acid (GA), a natural compound with broad anti-cancer activity, contains a highly reactive Michael acceptor at its C-10 position that limits clinical use by reacting non-selectively with biological nucleophiles. Two chemical modification strategies are evaluated to reduce this reactivity while preserving anticancer potency — one strategy proved more promising than the other. This is a purely cell-based in-vitro study with no molecular hydrogen (H₂) involvement.", "assessment": "This is an in-vitro medicinal chemistry study focused on optimising a natural antitumor compound. The results are relevant to oncology drug design but have no connection to molecular hydrogen (H₂) therapy. The paper appears in H₂ research databases due to keyword overlap with „hydrogen bond,“ a universal chemical concept entirely unrelated to dissolved molecular H₂. Findings are preliminary: cell-line efficacy does not predict clinical outcomes, and no animal studies are included.", "abstract": "Gambogic acid (GA), a natural product with unique structure, was reported to have broad antiproliferation activities against cancer cell lines. As a reactive Michael acceptor, the 10-position of GA is susceptible to nucleophiles, thus limiting its clinical application as an anticancer agent. Moreover, the 6-OH forms an intramolecular hydrogen bond with 8-CO, which can make the 9, 10 double bond more reactive to nucleophiles. In this essay, two strategies (A and B) were applied to solve the above-mentioned problems. Strategy A was to increase the steric hindrance of C-10 to reduce the activity of GA towards nucleophiles. Strategy B was to replace the hydroxyl of C-6 with other substituents based on the assumption that the intra-molecular hydrogen bond could increase the electrophilicity of C-10. Results showed the electrophilicity of C-10 disappeared as well as the antiproliferation activity against cancer cell lines by introducing a methyl group at C-10. Strategy B showed that the electrophilicity of C-10 was reduced dramatically while maintained the activity by replacement of the hydroxyl of C-6 with neutral or basic groups.", "conclusion": "Results showed the electrophilicity of C-10 disappeared as well as the antiproliferation activity against cancer cell lines by introducing a methyl group at C-10. Strategy B showed that the electrophilicity of C-10 was reduced dramatically while maintained the activity by replacement of the hydroxyl of C-6 with neutral or basic groups." }, { "pmid": "25962664", "year": 2015, "title": "Hydrogen gas production is associated with reduced interleukin-1β mRNA in peripheral blood after a single dose of acarbose in Japanese type 2 diabetic patients.", "title_en": null, "title_de": "Die Wasserstoffgasproduktion ist mit reduzierter Interleukin-1β-mRNA im peripheren Blut nach einer Einzeldosis Acarbose bei japanischen Typ-2-Diabetespatienten assoziiert.", "journal": "European journal of pharmacology", "authors": "Tamasawa et al.", "author_search": "tamasawa tamasawa", "doi": "10.1016/j.ejphar.2015.04.051", "doi_url": "https://doi.org/10.1016/j.ejphar.2015.04.051", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/25962664/", "url": "https://h2medicine.org/studies/study-tamasawa-2015-production-associated-reduced-interleukin/", "methods": [], "indications": [ "diabetes", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "byproduct", "headline": "2015 · Tamasawa et al. — Hydrogen gas production is associated with reduced interleukin-1β mRNA in peripheral blood after a single dose of acarbose in Japanese type 2 diabetic patients.", "summary": "In 16 type 2 diabetic patients, a single dose of the glucose-lowering drug acarbose did not significantly increase breath H₂ compared to no treatment — but the individual change in H₂ production was inversely associated with the change in blood IL-1β mRNA, suggesting a link between gut-produced H₂ and anti-inflammatory signaling. (European Journal of Pharmacology, 2015.)", "assessment": "A mechanistically innovative but methodologically limited pilot study. The primary endpoint was a null result, which the authors honestly report. The inverse correlation between H₂ production and IL-1β is hypothesis-generating but not proof of therapeutic effect. Limitations: n=16 is very small; single-dose, single-day design; no washout period; the indirect route (acarbose → gut bacteria → H₂ → blood IL-1β) has many confounders; the clinical significance of IL-1β mRNA changes from a single meal is uncertain. The study is interesting as a bridge between gut microbiome research, H₂ physiology, and metabolic inflammation.", "abstract": "Acarbose, an α-glucosidase inhibitor, leads to the production of hydrogen gas, which reduces oxidative stress. In this study, we examined the effects of a single dose of acarbose immediately before a test meal on postprandial hydrogen gas in breath and peripheral blood interleukin (IL)-1β mRNA expression in Japanese type 2 diabetic patients. Sixteen Japanese patients (14 men, 2 women) participated in this study. The mean±standard deviation age, hemoglobin A1c and body mass index were 52.1±15.4 years, 10.2±2.0%, and 27.7±8.0kg/m(2), respectively. The patients were admitted into our hospital for 2 days and underwent test meals at breakfast without (day 1) or with acarbose (day 2). We performed continuous glucose monitoring and measured hydrogen gas levels in breath, and peripheral blood IL-1β mRNA levels before (0min) and after the test meal (hydrogen gas: 60, 120, 180, and 300min; IL-1β: 180min). The induction of hydrogen gas production and the reduction in peripheral blood IL-1β mRNA after the test meal were not significant between days 1 (without acarbose) and 2 (with acarbose). However, the changes in total hydrogen gas production from day 1 to day 2 were closely and inversely associated with the changes in peripheral blood IL-1β mRNA levels. Our results suggest that an increase in hydrogen gas production is inversely associated with a reduction of the peripheral blood IL-1β mRNA level after a single dose of acarbose in Japanese type 2 diabetic patients.", "conclusion": "However, the changes in total hydrogen gas production from day 1 to day 2 were closely and inversely associated with the changes in peripheral blood IL-1β mRNA levels. Our results suggest that an increase in hydrogen gas production is inversely associated with a reduction of the peripheral blood IL-1β mRNA level after a single dose of acarbose in Japanese type 2 diabetic patients." }, { "pmid": "25947958", "year": 2015, "title": "Maternal molecular hydrogen treatment attenuates lipopolysaccharide-induced rat fetal lung injury.", "title_en": null, "title_de": "Mütterliche Behandlung mit molekularem Wasserstoff mildert die lipopolysaccharid-induzierte fetale Lungenschädigung bei Ratten.", "journal": "Free radical research", "authors": "Hattori et al.", "author_search": "hattori hattori", "doi": "10.3109/10715762.2015.1038257", "doi_url": "https://doi.org/10.3109/10715762.2015.1038257", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/25947958/", "url": "https://h2medicine.org/studies/study-hattori-2015-maternal-attenuates-lipopolysaccharide-induced/", "methods": [ "saline-iv" ], "indications": [ "cardiovascular", "respiratory", "immune-system", "pregnancy", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2015 · Hattori et al. — Maternal molecular hydrogen treatment attenuates lipopolysaccharide-induced rat fetal lung injury.", "summary": "Drinking hydrogen-rich water (HRW) before lipopolysaccharide (LPS) injection significantly reduced inflammation, oxidative damage, and cell death in fetal rat lungs — suggesting that maternal H₂ intake could protect premature infants from inflammation-driven lung disease. Both cell-culture (A549 line) and pregnant rat experiments were used. These are preclinical results and cannot be directly applied to human pregnancy.", "assessment": "A well-designed preclinical study with both in-vitro and in-vivo components. The consistent reduction of inflammatory and oxidative markers across both models strengthens the biological plausibility of H₂'s protective effect on fetal lungs. However, these are animal and cell results — no human data exist for antenatal H₂ administration. The jump from pregnant rat to pregnant woman is large: pharmacokinetics of H₂ transfer across the placenta, safety in first-trimester human pregnancy, and optimal dosing are entirely untested in humans. The findings are promising for basic research but cannot support clinical recommendations.", "abstract": "Maternal inflammation is associated with spontaneous preterm birth and respiratory impairment among premature infants. Recently, molecular hydrogen (H2) has been reported to have a suppressive effect on oxidative stress and inflammation. The aim of this study was to evaluate the effects of H2 on fetal lung injury caused by maternal inflammation. Cell viability and the production of interleukin-6 (IL-6) and reactive oxygen species (ROS) were examined by treatment with lipopolysaccharide (LPS) contained in ordinal or H2-rich medium (HM) using a human lung epithelial cell line, A549. Pregnant Sprague Dawley rats were divided into three groups: Control, LPS, and HW + LPS groups. Rats were injected with phosphate-buffered saline (Control) or LPS intraperitoneally (LPS) on gestational day 19 and provided H2 water (HW) ad libitum for 24 h before LPS injection (HW + LPS). Fetal lung samples were collected on day 20, and the levels of apoptosis, oxidative damage, IL-6, and vascular endothelial growth factor (VEGF) were evaluated using immunohistochemistry. The number of apoptotic cells, and levels of ROS and IL-6 were significantly increased by LPS treatment, and repressed following cultured with HM in A549 cells. In the rat models, the population positive for cleaved caspase-3, 8-hydroxy-2'-deoxyguanosine, IL-6, and VEGF was significantly increased in the LPS group compared with that observed in the Control group and significantly decreased in the HW + LPS group. In this study, LPS administration induced apoptosis and oxidative damage in fetal lung cells that was ameliorated by maternal H2 intake. Antenatal H2 administration may decrease the pulmonary mobility associated with inflammation in premature infants.", "conclusion": "In this study, LPS administration induced apoptosis and oxidative damage in fetal lung cells that was ameliorated by maternal H2 intake. Antenatal H2 administration may decrease the pulmonary mobility associated with inflammation in premature infants." }, { "pmid": "25936373", "year": 2015, "title": "Improvement of psoriasis-associated arthritis and skin lesions by treatment with molecular hydrogen: A report of three cases.", "title_en": null, "title_de": "Verbesserung der psoriasis-assoziierten Arthritis und Hautläsionen durch Behandlung mit molekularem Wasserstoff: Ein Bericht über drei Fälle.", "journal": "Molecular medicine reports", "authors": "Ishibashi et al.", "author_search": "ishibashi ishibashi", "doi": "10.3892/mmr.2015.3707", "doi_url": "https://doi.org/10.3892/mmr.2015.3707", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/25936373/", "url": "https://h2medicine.org/studies/study-ishibashi-2015-improvement-psoriasis-associated-arthritis/", "methods": [ "inhalation", "saline-iv", "drinking-hrw" ], "indications": [ "cancer", "skin-aging", "joints-rheumatology", "immune-system", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2015 · Ishibashi et al. — Improvement of psoriasis-associated arthritis and skin lesions by treatment with molecular hydrogen: A report of three cases.", "summary": "In three patients with psoriasis-associated arthritis and skin lesions, H₂ treatment (via saline infusion, inhalation, and/or high-concentration drinking water) reduced DAS28 and PASI scores, caused near-complete clearing of skin lesions, and lowered inflammatory cytokines (IL-6, IL-17, TNFα) in at least one patient. This is a case report series, not a controlled trial. (Molecular Medicine Reports, 2015.)", "assessment": "An intriguing case report series in an indication where H₂ has good mechanistic grounding (ROS in psoriasis cytokine cascade). The consistent improvement across three heterogeneous patients and delivery routes is noteworthy. Important limitations: n=3; no control; prior medications and their discontinuation not fully detailed; the dramatic skin clearing could involve regression to mean or prior treatment carryover effects; the different H₂ doses and routes make comparison impossible. A controlled trial in psoriasis with standardized H₂ delivery would be highly worthwhile.", "abstract": "Psoriasis, a chronic inflammatory skin disease, is caused by infiltrating lymphocytes and associated cytokines, including tumor necrosis factor (TNF)α, interleukin (IL)-6, and IL-17. Effective treatments, including pathogenesis-based biological agents against psoriasis, are currently under development. Although the role of reactive oxygen species (ROS) in the pathogenesis of psoriasis has been investigated, it remains to be fully elucidated; ROS-targeted therapeutic strategies are also lacking at present. Therefore, the objective of the present study was to assess whether H2, a ROS scavenger, has a therapeutic effect on psoriasis-associated inflammation by reducing hydroxyl radicals or peroxynitrite in the immunogenic psoriasis cascade. Three methods were used to administer H2: Drop infusion of saline containing 1 ppm H2 (H2-saline), inhalation of 3% H2 gas, and drinking of water containing a high concentration (5-7-ppm) of H2 (high-H2 water). Treatment efficacy was estimated using the disease activity score 28 (DAS28) system, based on C-reactive protein levels, and the psoriasis area and severity index (PASI) score, determined at baseline and following each H2 treatment. Furthermore, levels of TNFα, IL-6, and IL-17 were analyzed. The DAS28 and PASI score of the three patients decreased during H2 treatment, regardless of the administration method. The psoriatic skin lesions almost disappeared at the end of the treatment. IL-6 levels decreased during H2 treatment in Case 1 and 2. IL-17, whose concentration was high in Case 1, was reduced following H2 treatment, and TNFα also decreased in Case 1. In conclusion, H2 administration reduced inflammation associated with psoriasis in the three cases examined and it may therefore be considered as a treatment strategy for psoriasis-associated skin lesions and arthritis.", "conclusion": "IL-17, whose concentration was high in Case 1, was reduced following H2 treatment, and TNFα also decreased in Case 1. In conclusion, H2 administration reduced inflammation associated with psoriasis in the three cases examined and it may therefore be considered as a treatment strategy for psoriasis-associated skin lesions and arthritis." }, { "pmid": "25920542", "year": 2015, "title": "Eumelanin-driven production of molecular hydrogen: A novel element of skin defense?", "title_en": null, "title_de": "Eumelanin-gesteuerte Produktion von molekularem Wasserstoff: ein neues Element der Hautabwehr?", "journal": "Medical hypotheses", "authors": "Ostojic", "author_search": "ostojic ostojic", "doi": "10.1016/j.mehy.2015.04.014", "doi_url": "https://doi.org/10.1016/j.mehy.2015.04.014", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/25920542/", "url": "https://h2medicine.org/studies/study-ostojic-2015-eumelanin-driven-production-element/", "methods": [ "unspecified" ], "indications": [ "skin-aging", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2015 · Ostojic — Eumelanin-driven production of molecular hydrogen: A novel element of skin defense?", "summary": "This theoretical hypothesis paper proposes that eumelanin — the dark pigment in skin and hair — may produce endogenous molecular hydrogen (H₂) and that this capacity could represent a previously overlooked mechanism of skin protection against oxidative stress. No experiments were conducted; this is a speculative hypothesis based on existing knowledge of melanin chemistry and H₂ biology, published in a hypotheses journal.", "assessment": "This is a theoretical hypothesis paper — no experiments, no animal models, no human subjects. The idea that eumelanin generates biologically relevant quantities of H₂ in skin is novel and intellectually interesting, but it has not been experimentally tested. Until direct measurement of eumelanin-generated H₂ under physiological conditions is demonstrated, this remains speculation. The Medical Hypotheses journal specifically exists for unvalidated ideas, which means the paper has not passed standard peer-review experimental scrutiny. It should be read as a hypothesis-generating paper, not as evidence.", "abstract": "Molecular hydrogen (H2, dihydrogen) has been recognized as a unique cell protectant. Dihydrogen protects tissues against oxidative injuries by selectively reducing reactive oxygen species (ROS). It seems that melanin, natural pigment of skin and hair, might produce endogenous hydrogen. The protective role of skin melanin (eumelanin) could be due to its capacity for molecular hydrogen production. An effective pooling of dihydrogen by eumelanin should be considered as a novel element of skin defense system against oxidative stress-related disorders.", "conclusion": "The protective role of skin melanin (eumelanin) could be due to its capacity for molecular hydrogen production. An effective pooling of dihydrogen by eumelanin should be considered as a novel element of skin defense system against oxidative stress-related disorders." }, { "pmid": "25895142", "year": 2015, "title": "Hydrogen-Rich Medium Attenuated Lipopolysaccharide-Induced Monocyte-Endothelial Cell Adhesion and Vascular Endothelial Permeability via Rho-Associated Coiled-Coil Protein Kinase.", "title_en": null, "title_de": "Wasserstoffreiches Medium schwächte die Lipopolysaccharid-induzierte Monozyten-Endothelzell-Adhäsion und die vaskuläre Endothelpermeabilität über die Rho-assoziierte Coiled-Coil-Proteinkinase ab.", "journal": "Shock (Augusta, Ga.)", "authors": "Xie et al.", "author_search": "xie xie", "doi": "10.1097/shk.0000000000000365", "doi_url": "https://doi.org/10.1097/shk.0000000000000365", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/25895142/", "url": "https://h2medicine.org/studies/study-xie-2015-medium-attenuated-lipopolysaccharide-induced/", "methods": [ "unspecified" ], "indications": [ "cardiovascular", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2015 · Xie et al. — Hydrogen-Rich Medium Attenuated Lipopolysaccharide-Induced Monocyte-Endothelial Cell Adhesion and Vascular Endothelial Permeability via Rho-Associated Coiled-Coil Protein Kinase.", "summary": "In LPS-stimulated endothelial cell cultures, hydrogen-rich medium (H₂-RM) blocked monocyte-to-endothelium adhesion, decreased expression of adhesion molecules, and restored vascular barrier function — all via suppression of the ROCK signalling pathway. A parallel effect on neutrophil adhesion was also observed. This is a cell-culture (in-vitro) study; findings cannot be directly applied to human sepsis therapy.", "assessment": "A focused in-vitro mechanistic study with clear, internally consistent results. The ROCK pathway is a well-validated target in vascular biology, and linking H₂'s anti-inflammatory action to ROCK suppression adds mechanistic depth to H₂ research. Limitations are significant: this is a cell-culture study only. LPS stimulation of cultured endothelial cells is a simplification of the complex in-vivo sepsis environment. Whether drinking H₂ water or inhaling H₂ gas achieves sufficient local H₂ concentrations in vascular endothelium in vivo — and whether ROCK suppression mediates this effect in living organisms — is not yet established. These results justify follow-up animal studies.", "abstract": "Sepsis is the leading cause of death in critically ill patients. In recent years, molecular hydrogen, as an effective free radical scavenger, has been shown a selective antioxidant and anti-inflammatory effect, and it is beneficial in the treatment of sepsis. Rho-associated coiled-coil protein kinase (ROCK) participates in junction between normal cells, and regulates vascular endothelial permeability. In this study, we used lipopolysaccharide to stimulate vascular endothelial cells and explored the effects of hydrogen-rich medium on the regulation of adhesion of monocytes to endothelial cells and vascular endothelial permeability. We found that hydrogen-rich medium could inhibit adhesion of monocytes to endothelial cells and decrease levels of adhesion molecules, whereas the levels of transepithelial/endothelial electrical resistance values and the expression of vascular endothelial cadherin were increased after hydrogen-rich medium treatment. Moreover, hydrogen-rich medium could lessen the expression of ROCK, as a similar effect of its inhibitor Y-27632. In addition, hydrogen-rich medium could also inhibit adhesion of polymorphonuclear neutrophils to endothelial cells. In conclusion, hydrogen-rich medium could regulate adhesion of monocytes/polymorphonuclear neutrophils to endothelial cells and vascular endothelial permeability, and this effect might be related to the decreased expression of ROCK protein.", "conclusion": "In addition, hydrogen-rich medium could also inhibit adhesion of polymorphonuclear neutrophils to endothelial cells. In conclusion, hydrogen-rich medium could regulate adhesion of monocytes/polymorphonuclear neutrophils to endothelial cells and vascular endothelial permeability, and this effect might be related to the decreased expression of ROCK protein." }, { "pmid": "25812363", "year": 2015, "title": "[Alpha-glucosidase inhibitor].", "title_en": null, "title_de": "[Alpha-Glucosidase-Hemmer]. (Nihon Rinsho)", "journal": "Nihon rinsho. Japanese journal of clinical medicine", "authors": "Osonoi", "author_search": "osonoi osonoi", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/25812363/", "url": "https://h2medicine.org/studies/study-osonoi-2015-alpha-glucosidase-inhibitor/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "sports-exercise", "cardiovascular" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2015 · Osonoi — [Alpha-glucosidase inhibitor]. (Nihon Rinsho)", "summary": "This Japanese-language clinical review discusses alpha-glucosidase inhibitors (α-GI) — a class of oral antidiabetic drugs — noting that their characteristic intestinal side effects (gas, bloating) arise from hydrogen gas produced by gut bacteria fermenting undigested carbohydrates. The review also covers synergies of α-GI with newer antidiabetic drug classes. It is a literature review, not an original study.", "assessment": "This is a narrative review article in a Japanese clinical journal — it synthesises existing knowledge rather than generating new data. The H₂-related claim (intestinal H₂ from α-GI fermentation may protect against arteriosclerosis) is plausible and aligns with the broader H₂ biology literature, but it is a hypothesis within the review, not a tested endpoint. Limitations: no systematic literature search, no pooled effect sizes, no risk-of-bias assessment. The primary value is as a clinically oriented overview of α-GI pharmacology and combination therapy options — not as evidence for H₂ supplementation.", "abstract": "Alpha-glucosidase inhibitors (α-GI) have abdominal signs which are generally regarded as side-reaction. The abdominal signs are caused by generation of intestinal gas which contains hydrogen gas. The hydrogen gas absorbed in the body eliminates oxidant stress and consequently the abdominal signs may have beneficial effects preventing onset and progression of arteriosclerosis. Recently, it has been reported that the combination therapy of dipeptidyl peptidase-4 inhibitors with a-GI enhances glucagon like peptide-1 (GLP- 1) secretion and increases active GLP-1 concentration. Therefore, α-GI is not only a matured and reliable oral anti-diabtic agent (OAD) but also a promising OAD which collaborates effectively with DPP-4 inhibitors or sodium-glucose cotransporter-2 inhibitors.", "conclusion": "Recently, it has been reported that the combination therapy of dipeptidyl peptidase-4 inhibitors with a-GI enhances glucagon like peptide-1 (GLP- 1) secretion and increases active GLP-1 concentration. Therefore, α-GI is not only a matured and reliable oral anti-diabtic agent (OAD) but also a promising OAD which collaborates effectively with DPP-4 inhibitors or sodium-glucose cotransporter-2 inhibi" }, { "pmid": "25800452", "year": 2015, "title": "Hydrogen Therapy Reduces Oxidative Stress-associated Risks Following Acute and Chronic Exposure to High-altitude Environment.", "title_en": null, "title_de": "Wasserstofftherapie reduziert mit oxidativem Stress assoziierte Risiken nach akuter und chronischer Exposition gegenüber einer Höhenumgebung.", "journal": "Biomedical and environmental sciences : BES", "authors": "Shi et al.", "author_search": "shi shi", "doi": "10.3967/bes2015.034", "doi_url": "https://doi.org/10.3967/bes2015.034", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/25800452/", "url": "https://h2medicine.org/studies/study-shi-2015-reduces-oxidative-stress-associated/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "cancer", "skin-aging", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2015 · Shi et al. — Hydrogen Therapy Reduces Oxidative Stress-associated Risks Following Acute and Chronic Exposure to High-altitude Environment.", "summary": "This theoretical paper proposes that inhaling low-dose H₂ gas or drinking hydrogen-saturated water could prevent and treat mountain sickness by counteracting the oxidative stress caused by high-altitude low-oxygen and high-UV conditions. The authors argue that H₂'s selective free-radical scavenging and anti-inflammatory properties make it a novel and practical candidate for altitude medicine. No experiments were conducted — this is a reasoned hypothesis.", "assessment": "This is a theoretical hypothesis paper with no original experimental data. The underlying biological reasoning is sound — H₂ is a selective antioxidant, high altitude generates ROS, and H₂ is easily deliverable — but the specific hypothesis (H₂ prevents altitude sickness) has not been tested in controlled trials. Until properly designed human or animal altitude studies are conducted, this remains an educated conjecture. The paper's value is as a rationale for future research, not as evidence of efficacy. No clinical recommendations can be derived from it.", "abstract": "Low pressure, low oxygen concentration, and intense ultraviolet (UV) radiation in high-altitude environments, can cause oxidative stress which can trigger mountain sickness. A recent study demonstrated that hydrogen gas with a good permeability in biological membranes can treat various disorders by exerting its selective anti-oxidation and anti-inflammatory effects, indicating that hydrogen therapy plays a role in scavenging free radicals and in balancing oxidation and anti-oxidation systems of cells. Therefore, we hypothesize that inhaling low-dose hydrogen or drinking hydrogen-saturated water is a novel and simple method to prevent and treat oxidative stress injury caused by low pressure, low oxygen concentration and intense UV radiation in plateaus, thus reducing the risk of mountain sickness.", "conclusion": "A recent study demonstrated that hydrogen gas with a good permeability in biological membranes can treat various disorders by exerting its selective anti-oxidation and anti-inflammatory effects, indicating that hydrogen therapy plays a role in scavenging free radicals and in balancing oxidation and anti-oxidation systems of cells. Therefore, we hypothesize that inhaling low-dose hydrogen or drinki" }, { "pmid": "25767993", "year": 2015, "title": "Synthesis, spectral characterization, thermal behaviour, antibacterial activity and DFT calculation on N'-[bis(methylsulfanyl) methylene]-2-hydroxybenzohydrazide and N'-(4-methoxy benzoyl)-hydrazinecarbodithioic acid ethyl ester.", "title_en": null, "title_de": "Synthese, spektrale Charakterisierung, thermisches Verhalten, antibakterielle Aktivität und DFT-Berechnung an N'-[Bis(methylsulfanyl)methylen]-2-hydroxybenzohydrazid und N'-(4-Methoxybenzoyl)-hydrazincarbodithionsäure-ethylester.", "journal": "Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy", "authors": "Bharty et al.", "author_search": "bharty bharty", "doi": "10.1016/j.saa.2015.02.055", "doi_url": "https://doi.org/10.1016/j.saa.2015.02.055", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/25767993/", "url": "https://h2medicine.org/studies/study-bharty-2015-synthesis-spectral-characterization-thermal/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2015 · Bharty et al. — Synthesis, spectral characterization, thermal behaviour, antibacterial activity and DFT calculation on N'-[bis(methylsulfanyl)methylene]-2-hydroxybenzohydrazide and N'-(4-methoxybenzoyl)-hydrazinecarbodithioic acid ethyl ester.", "summary": "Two new synthetic compounds based on hydrazone scaffolds were characterised by X-ray crystallography, NMR, IR, and thermal analysis; both showed antibacterial activity and nonlinear optical (NLO) properties superior to urea. Density functional theory (DFT) calculations confirmed the molecular geometry and electronic properties. This is a pure synthetic chemistry / in-vitro study with no connection to molecular hydrogen (H₂) biology.", "assessment": "This is a synthetic chemistry and materials science study — it reports the characterisation of new compounds with potential in antimicrobial drug design and photonics/NLO applications. It has zero relevance to molecular hydrogen (H₂) medicine or therapy. Its inclusion in H₂ research databases is a false-positive from keyword matching on „hydrogen bonding.“ The antibacterial activity results are preliminary (in-vitro MIC-type screening only) and provide no clinical evidence.", "abstract": "Two new compounds N'-[bis(methylsulfanyl) methylene]-2-hydroxybenzohydrazide {Hbmshb (1)} and N'-(4-methoxy benzoyl)-hydrazinecarbodithioic acid ethyl ester {H2mbhce (2)} have been synthesized and characterized with the aid of elemental analyses, IR, NMR and single crystal X-ray diffraction data. Compounds 1 and 2 crystallize in orthorhombic and monoclinic systems with space group Pna21 and P21/n, respectively. Inter and intra molecular hydrogen bonding link two molecules and provide linear chain structure. In addition to this, compound 2 is stabilized by CH⋯π and NH⋯π interactions. Molecular geometry from X-ray analysis, geometry optimization, charge distribution, bond analysis, frontier molecular orbital (FMO) analysis and non-linear optical (NLO) effects have been performed using the density functional theory (DFT) with the B3LYP functional. The bioefficacy of compounds has been examined against the growth of bacteria to evaluate their anti-microbial potential. Compounds 1 and 2 are thermally stable and show NLO behaviour better than the urea crystal.", "conclusion": "The bioefficacy of compounds has been examined against the growth of bacteria to evaluate their anti-microbial potential. Compounds 1 and 2 are thermally stable and show NLO behaviour better than the urea crystal." }, { "pmid": "25758062", "year": 2015, "title": "Prediction of binding modes between protein L-isoaspartyl (D-aspartyl) O-methyltransferase and peptide substrates including isomerized aspartic acid residues using in silico analytic methods for the substrate screening.", "title_en": null, "title_de": "Vorhersage der Bindungsmodi zwischen Protein-L-Isoaspartyl-(D-Aspartyl)-O-Methyltransferase und Peptidsubstraten mit isomerisierten Asparaginsäureresten unter Verwendung von In-silico-Analysemethoden für das Substrat-Screening.", "journal": "Journal of pharmaceutical and biomedical analysis", "authors": "Oda et al.", "author_search": "oda oda", "doi": "10.1016/j.jpba.2015.02.030", "doi_url": "https://doi.org/10.1016/j.jpba.2015.02.030", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/25758062/", "url": "https://h2medicine.org/studies/study-oda-2015-prediction-binding-modes-between/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2015 · Oda et al. — Prediction of binding modes between protein L-isoaspartyl (D-aspartyl) O-methyltransferase and peptide substrates including isomerized aspartic acid residues using in silico analytic methods for the substrate screening.", "summary": "Computational docking and molecular dynamics simulation successfully predicted how the DNA-repair enzyme PIMT recognises isomerised aspartic acid variants in peptide substrates — distinguishing true substrates from non-substrates purely in silico. The method could accelerate substrate screening in aging and protein-damage research. This study has no connection to molecular hydrogen (H₂) biology.", "assessment": "A well-executed computational study in structural enzymology. The finding that in-silico methods can distinguish PIMT substrates from non-substrates has practical value for high-throughput substrate screening in aging-related protein-damage research. The study has no relevance to molecular hydrogen (H₂) medicine; it deals with hydrogen bonds as a fundamental biochemical concept. Its presence in H₂ databases reflects keyword matching artefact, not scientific relevance to H₂ therapy.", "abstract": "Because the aspartic acid (Asp) residues in proteins are occasionally isomerized in the human body, not only l-α-Asp but also l-β-Asp, D-α-Asp and D-β-Asp are found in human proteins. In these isomerized aspartic acids, the proportion of D-β-Asp is the largest and the proportions of l-β-Asp and D-α-Asp found in human proteins are comparatively small. To explain the proportions of aspartic acid isomers, the possibility of an enzyme able to repair l-β-Asp and D-α-Asp is frequently considered. The protein L-isoaspartyl (D-aspartyl) O-methyltransferase (PIMT) is considered one of the possible repair enzymes for l-β-Asp and D-α-Asp. Human PIMT is an enzyme that recognizes both l-β-Asp and D-α-Asp, and catalyzes the methylation of their side chains. In this study, the binding modes between PIMT and peptide substrates containing l-β-Asp or D-α-Asp residues were investigated using computational protein-ligand docking and molecular dynamics simulations. The results indicate that carboxyl groups of both l-β-Asp and D-α-Asp were recognized in similar modes by PIMT and that the C-terminal regions of substrate peptides were located in similar positions on PIMT for both the l-β-Asp and D-α-Asp peptides. In contrast, for peptides containing l-α-Asp or D-β-Asp residues, which are not substrates of PIMT, the computationally constructed binding modes between PIMT and peptides greatly differed from those between PIMT and substrates. In the nonsubstrate peptides, not inter- but intra-molecular hydrogen bonds were observed, and the conformations of peptides were more rigid than those of substrates. Thus, the in silico analytical methods were able to distinguish substrates from nonsubstrates and the computational methods are expected to complement experimental analytical methods.", "conclusion": "In the nonsubstrate peptides, not inter- but intra-molecular hydrogen bonds were observed, and the conformations of peptides were more rigid than those of substrates. Thus, the in silico analytical methods were able to distinguish substrates from nonsubstrates and the computational methods are expected to complement experimental analytical methods." }, { "pmid": "25708582", "year": 2015, "title": "Diversity of human-associated Methanobrevibacter smithii isolates revealed by multispacer sequence typing.", "title_en": null, "title_de": "Diversität von mit dem Menschen assoziierten Methanobrevibacter-smithii-Isolaten, aufgedeckt durch Multispacer-Sequenztypisierung.", "journal": "Current microbiology", "authors": "Nkamga et al.", "author_search": "nkamga nkamga", "doi": "10.1007/s00284-015-0787-9", "doi_url": "https://doi.org/10.1007/s00284-015-0787-9", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/25708582/", "url": "https://h2medicine.org/studies/study-nkamga-2015-diversity-associated-methanobrevibacter-smithii/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2015 · Nkamga et al. — Diversity of human-associated Methanobrevibacter smithii isolates revealed by multispacer sequence typing.", "summary": "A new genotyping method (multispacer sequence typing, MST) applied to Methanobrevibacter smithii — the main hydrogen-consuming archaeon in the human gut — revealed 15 distinct genetic variants among isolates from oral cavity and gut of 12 individuals. Multiple genotypes can coexist in a single person at the same anatomical site. This is a microbiology / sequencing study; it does not investigate therapeutic molecular hydrogen (H₂).", "assessment": "A solid microbiology methods study that develops a useful genotyping tool for the gut archaeome. The H₂ connection is biological background (M. smithii metabolises gut H₂) rather than a therapeutic investigation. This study does not examine whether consuming gut H₂ before M. smithii can act on human health, nor does it test any H₂ therapy. It is relevant to microbiome research and archaeal population genetics; its presence in H₂ therapy databases reflects the broader research ecosystem around endogenous H₂ metabolism.", "abstract": "Methanobrevibacter smithii is the main archaea in human, detoxifying molecular hydrogen resulting from anaerobic bacteria fermentations into gaseous methane. Its identification relies on gene sequencing, but no method is available to discriminate among genetic variants of M. smithii. Here, we developed a multispacer sequence typing (MST) for genotyping the genetic variants of M. smithii. Four intergenic spacers recovered from the M. smithii reference genome were PCR amplified and sequenced in three M. smithii reference strains and in a collection of 22 M. smithii isolates from the oral cavity in two individuals and the gut of 10 additional individuals. Sequencing yielded 216 genetic polymorphisms including 89 single nucleotide polymorphisms (41.2 %), 83 insertions (38.4 %), and 44 deletions (20.4 %). Combining these genetic polymorphisms yielded 15 genotypes with an index of discrimination of 0.942 (confidence interval 0.9-0.984; P < 0.05). Five M. smithii isolates made from the oral cavity yielded five different genotypes; seven gut isolates yielded nine different genotypes; genotypes MST5 and MST6 were found both in the oral cavity and the gut. Multiple genotypes were identified in some individuals at the same anatomical site. MST is a sequencing-based method which discriminates several genetic variants within M. smithii. Individuals may harbor several contemporary genetic variants of M. smithii in the oral cavity and gut. MST will allow studying population dynamics of M. smithii and tracing its circulation between individuals and their environment.", "conclusion": "MST will allow studying population dynamics of M. smithii and tracing its circulation between individuals and their environment." }, { "pmid": "25681223", "year": 2015, "title": "Effects of vitamin C, vitamin E, and molecular hydrogen on the placental function in trophoblast cells.", "title_en": null, "title_de": "Wirkungen von Vitamin C, Vitamin E und molekularem Wasserstoff auf die Plazentafunktion in Trophoblastenzellen.", "journal": "Archives of gynecology and obstetrics", "authors": "Guan et al.", "author_search": "guan guan", "doi": "10.1007/s00404-015-3647-8", "doi_url": "https://doi.org/10.1007/s00404-015-3647-8", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/25681223/", "url": "https://h2medicine.org/studies/study-guan-2015-vitamin-vitamin-placental-function/", "methods": [ "unspecified" ], "indications": [ "cancer", "pregnancy", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2015 · Guan et al. — Effects of vitamin C, vitamin E, and molecular hydrogen on the placental function in trophoblast cells.", "summary": "In cultured trophoblast cell lines, high doses of vitamins C and E reduced cell viability and increased the pro-inflammatory cytokine TNF-α — whereas molecular hydrogen (H₂) at equivalent concentrations did neither, suggesting a more favourable safety profile for H₂ as an antioxidant in placental biology. However, H₂ did suppress hCG secretion, warranting further investigation. These are in-vitro findings only; no human pregnancy data.", "assessment": "A useful in-vitro comparative study that provides a mechanistic rationale for why H₂ may be a safer antioxidant option than vitamins C and E in placental biology. The safety advantage (no cytotoxicity, no TNF-α elevation) is a meaningful differentiator. However, the unexpected suppression of hCG secretion by H₂ is an important cautionary finding that has not yet been explained or replicated. This study is strictly in-vitro — cell lines do not capture the full complexity of human placenta. No conclusions about safety or efficacy in pregnant women can be drawn. Further animal and clinical studies are required.", "abstract": "AIM: This study aimed to investigate the effects of three different antioxidants, namely vitamin C, vitamin E, and molecular hydrogen, on cytotrophoblasts in vitro. METHODS: Two trophoblast cell lines, JAR and JEG-3, were exposed to different concentrations of vitamin C (0, 25, 50, 100, 500, 1,000, 5,000 μmol/L), vitamin E (0, 25, 50, 100, 500, 1,000, 5,000 μmol/L), and molecular hydrogen (0, 25, 50, 100, 500 μmol/L) for 48 h. The cell viability was detected using the MTS assay. The secretion of human chorionic gonadotropin (hCG) and the tumor necrosis factor-α (TNF-α) were assessed and the expression of TNF-α mRNA was observed by real-time RT-PCR. RESULTS: Cell viability was significantly suppressed by 500 μmol/L vitamins C and E (P < 0.05), but not by 500 μmol/L molecular hydrogen (P > 0.05). The expression of TNF-α was increased by 100 μmol/L vitamin C and 50 μmol/L vitamins E, separately or combined (P < 0.05), but not by molecular hydrogen (0-500 μmol/L), as validated by real-time RT-PCR. But the secretion of hCG was both inhibited by 50-500 μmol/L molecular hydrogen and high levels of vitamin C and E, separately or combined. CONCLUSION: High levels of antioxidant vitamins C and E may have significant detrimental effects on placental function, as reflected by decreased cell viability and secretion of hCG; and placental immunity, as reflected by increased production of TNF-a. Meanwhile hydrogen showed no such effects on cell proliferation and TNF-α expression, but it could affect the level of hCG, indicating hydrogen as a potential candidate of antioxidant in the management of preeclampsia (PE) should be further studied.", "conclusion": "High levels of antioxidant vitamins C and E may have significant detrimental effects on placental function, as reflected by decreased cell viability and secretion of hCG; and placental immunity, as reflected by increased production of TNF-a. Meanwhile hydrogen showed no such effects on cell proliferation and TNF-α expression, but it could affect the level of hCG, indicating hydrogen as a potential candidate of antioxidant in the management of preeclampsia (PE) should be further studied." }, { "pmid": "25468479", "year": 2015, "title": "Can an innocent toy become dangerous? The hydrogen gas balloon burn.", "title_en": null, "title_de": "Kann ein harmloses Spielzeug gefährlich werden? Die Wasserstoffgasballon-Verbrennung.", "journal": "Burns : journal of the International Society for Burn Injuries", "authors": "Keles et al.", "author_search": "keles keles", "doi": "10.1016/j.burns.2014.10.011", "doi_url": "https://doi.org/10.1016/j.burns.2014.10.011", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/25468479/", "url": "https://h2medicine.org/studies/study-keles-2015-can-innocent-toy-become/", "methods": [ "inhalation" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2015 · Keles et al. — Can an innocent toy become dangerous? The hydrogen gas balloon burn.", "summary": "Hydrogen gas, used to fill balloons, can ignite and cause severe burns — a safety risk that is rarely discussed. This theoretical case report analyses how a seemingly harmless toy balloon can become a source of serious injury when the hydrogen gas it contains is accidentally ignited.", "assessment": "No abstract is publicly available for this paper. This is a theoretical/case-based safety report, not a study of hydrogen's therapeutic effects. It addresses a physical injury risk (balloon combustion) rather than H₂ biology. No data on humans or animals in a biomedical sense are presented. The findings are not relevant to the evaluation of molecular hydrogen as a health intervention.", "abstract": null, "conclusion": null }, { "pmid": "25446368", "year": 2015, "title": "The use of hydrogen gas clearance for blood flow measurements in single endogenous and transplanted pancreatic islets.", "title_en": null, "title_de": "Die Verwendung der Wasserstoffgas-Clearance zur Messung des Blutflusses in einzelnen endogenen und transplantierten Pankreasinseln.", "journal": "Microvascular research", "authors": "Barbu et al.", "author_search": "barbu barbu", "doi": "10.1016/j.mvr.2014.10.002", "doi_url": "https://doi.org/10.1016/j.mvr.2014.10.002", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/25446368/", "url": "https://h2medicine.org/studies/study-barbu-2015-use-clearance-blood-flow/", "methods": [ "inhalation" ], "indications": [ "cardiovascular", "kidney-dialysis" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2015 · Barbu et al. — The use of hydrogen gas clearance for blood flow measurements in single endogenous and transplanted pancreatic islets.", "summary": "Researchers used hydrogen gas as a tracer — not as therapy — to precisely measure blood flow in individual pancreatic islets in rats and mice. This animal study revealed that blood perfusion within a single pancreas varies enormously (by a factor of 6–10) between islets, and that transplanted human and mouse islets receive about 30 % less blood flow than the surrounding kidney tissue.", "assessment": "This is a methodological animal study — H₂ is used as a physiological tracer, not as a therapeutic intervention. The findings are relevant to pancreatic islet biology and transplantation science. Important limitations: all experiments were conducted in rats and athymic mice; results cannot be directly transferred to human physiology. The study does not evaluate any health benefit of molecular hydrogen as a consumed substance.", "abstract": "The blood perfusion of pancreatic islets is regulated independently from that of the exocrine pancreas, and is of importance for multiple aspects of normal islet function, and probably also during impaired glucose tolerance. Single islet blood flow has been difficult to evaluate due to technical limitations. We therefore adapted a hydrogen gas washout technique using microelectrodes to allow such measurements. Platinum micro-electrodes monitored hydrogen gas clearance from individual endogenous and transplanted islets in the pancreas of male Lewis rats and in human and mouse islets implanted under the renal capsule of male athymic mice. Both in the rat endogenous pancreatic islets as well as in the intra-pancreatically transplanted islets, the vascular conductance and blood flow values displayed a highly heterogeneous distribution, varying by factors 6-10 within the same pancreas. The blood flow of human and mouse islet grafts transplanted in athymic mice was approximately 30% lower than that in the surrounding renal parenchyma. The present technique provides unique opportunities to study the islet vascular dysfunction seen after transplantation, but also allows for investigating the effects of genetic and environmental perturbations on islet blood flow at the single islet level in vivo.", "conclusion": "The blood flow of human and mouse islet grafts transplanted in athymic mice was approximately 30% lower than that in the surrounding renal parenchyma. The present technique provides unique opportunities to study the islet vascular dysfunction seen after transplantation, but also allows for investigating the effects of genetic and environmental perturbations on islet blood flow at the single islet " }, { "pmid": "25411171", "year": 2015, "title": "Campylobacter concisus pseudo-outbreak caused by improved culture conditions.", "title_en": null, "title_de": "Campylobacter-concisus-Pseudoausbruch verursacht durch verbesserte Kulturbedingungen.", "journal": "Journal of clinical microbiology", "authors": "Casanova et al.", "author_search": "casanova casanova", "doi": "10.1128/jcm.02608-14", "doi_url": "https://doi.org/10.1128/jcm.02608-14", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/25411171/", "url": "https://h2medicine.org/studies/study-casanova-2015-campylobacter-concisus-pseudo-outbreak/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2015 · Casanova et al. — Campylobacter concisus pseudo-outbreak caused by improved culture conditions.", "summary": "A hospital in Bern noticed a sudden rise in Campylobacter concisus detections — but it turned out to be a pseudo-outbreak caused by switching to a hydrogen-enriched atmosphere in the lab, which made the bacterium grow far better. No real infection cluster existed; a change in microbiological culture conditions was the sole cause of the apparent surge.", "assessment": "This is a microbiological in-vitro/laboratory investigation. Hydrogen appears here solely as an ingredient of a bacterial growth atmosphere — not as a substance consumed by humans for health purposes. The study contributes to clinical microbiology methodology but has no relevance to molecular hydrogen therapy or supplementation.", "abstract": "An unusual increase in the number of Campylobacter concisus isolates found in stool cultures provoked an outbreak investigation at Bern University Hospital. No epidemiological links were found between the cases, and the Campylobacter isolates were clonally unrelated. A change in culture conditions to a hydrogen-rich atmosphere enhancing growth of C. concisus was deemed responsible for this pseudo-outbreak.", "conclusion": "A change in culture conditions to a hydrogen-rich atmosphere enhancing growth of C. concisus was deemed responsible for this pseudo-outbreak." }, { "pmid": "24829918", "year": 2014, "title": "Hydrogen gas presents a promising therapeutic strategy for sepsis.", "title_en": null, "title_de": "Wasserstoffgas stellt eine vielversprechende therapeutische Strategie für Sepsis dar.", "journal": "BioMed research international", "authors": "Xie et al.", "author_search": "xie xie", "doi": "10.1155/2014/807635", "doi_url": "https://doi.org/10.1155/2014/807635", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/24829918/", "url": "https://h2medicine.org/studies/study-xie-2014-presents-promising-therapeutic-strategy/", "methods": [ "inhalation" ], "indications": [ "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2014 · Xie et al. — Hydrogen gas presents a promising therapeutic strategy for sepsis.", "summary": "This review summarises preclinical evidence that inhaled molecular hydrogen (H₂) improved survival and reduced organ damage in animal models of sepsis. The authors propose that H₂ acts via antioxidant, anti-inflammatory, and anti-apoptotic pathways — particularly through NF-κB and Nrf2/HO-1 signalling — but this remains entirely animal-level evidence with no confirmed human data.", "assessment": "This is a narrative review of preclinical (animal) studies. It presents a coherent mechanistic rationale for H₂ in sepsis, but the evidence base is entirely rodent data. Key limitations: no human clinical trials are reviewed; the paper is largely self-referential (authors reviewing their own prior work); and it does not perform systematic literature search or meta-analysis. The hypothesis is scientifically interesting, but H₂ cannot be considered a proven therapy for sepsis in humans based on this review alone.", "abstract": "Sepsis is characterized by a severe inflammatory response to infection. It remains a major cause of morbidity and mortality in critically ill patients despite developments in monitoring devices, diagnostic tools, and new therapeutic options. Recently, some studies have found that molecular hydrogen is a new therapeutic gas. Our studies have found that hydrogen gas can improve the survival and organ damage in mice and rats with cecal ligation and puncture, zymosan, and lipopolysaccharide-induced sepsis. The mechanisms are associated with the regulation of oxidative stress, inflammatory response, and apoptosis, which might be through NF- κ B and Nrf2/HO-1 signaling pathway. In this paper, we summarized the progress of hydrogen treatment in sepsis.", "conclusion": "The mechanisms are associated with the regulation of oxidative stress, inflammatory response, and apoptosis, which might be through NF- κ B and Nrf2/HO-1 signaling pathway. In this paper, we summarized the progress of hydrogen treatment in sepsis." }, { "pmid": "24769081", "year": 2014, "title": "Molecular hydrogen as a preventive and therapeutic medical gas: initiation, development and potential of hydrogen medicine.", "title_en": null, "title_de": "Molekularer Wasserstoff als präventives und therapeutisches medizinisches Gas: Beginn, Entwicklung und Potenzial der Wasserstoffmedizin.", "journal": "Pharmacology & therapeutics", "authors": "Ohta", "author_search": "ohta ohta", "doi": "10.1016/j.pharmthera.2014.04.006", "doi_url": "https://doi.org/10.1016/j.pharmthera.2014.04.006", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/24769081/", "url": "https://h2medicine.org/studies/study-ohta-2014-preventive-therapeutic-medical-initiation/", "methods": [ "inhalation", "saline-iv", "bath-topical", "drinking-hrw" ], "indications": [ "eye", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2014 · Ohta — Molecular hydrogen as a preventive and therapeutic medical gas: initiation, development and potential of hydrogen medicine.", "summary": "One of the founding papers of hydrogen medicine, authored by Shigeo Ohta, summarises how H₂ was discovered to react with harmful hydroxyl radicals in cells — and why this makes it a candidate for preventing and treating a wide range of diseases. The review covers multiple delivery routes, animal experiments, and early clinical examinations, while acknowledging that serious human evidence is still accumulating.", "assessment": "This is an influential narrative review by a founder of the field, offering a broad synthesis of H₂ biology and early clinical data. Its strength is mechanistic depth and historical context. Limitations: it is not a systematic review or meta-analysis; the author is deeply invested in the field; clinical evidence cited ranges from strong to very preliminary. The paper correctly characterises H₂ research as promising but not yet conclusive for most human disease applications — a position that remains accurate today.", "abstract": "Molecular hydrogen (H2) has been accepted to be an inert and nonfunctional molecule in our body. We have turned this concept by demonstrating that H2 reacts with strong oxidants such as hydroxyl radical in cells, and proposed its potential for preventive and therapeutic applications. H2 has a number of advantages exhibiting extensive effects: H2 rapidly diffuses into tissues and cells, and it is mild enough neither to disturb metabolic redox reactions nor to affect signaling reactive oxygen species; therefore, there should be no or little adverse effects of H2. There are several methods to ingest or consume H2; inhaling H2 gas, drinking H2-dissolved water (H2-water), injecting H2-dissolved saline (H2-saline), taking an H2 bath, or dropping H2-saline into the eyes. The numerous publications on its biological and medical benefits revealed that H2 reduces oxidative stress not only by direct reactions with strong oxidants, but also indirectly by regulating various gene expressions. Moreover, by regulating the gene expressions, H2 functions as an anti-inflammatory and anti-apoptotic, and stimulates energy metabolism. In addition to growing evidence obtained by model animal experiments, extensive clinical examinations were performed or are under investigation. Since most drugs specifically act to their targets, H2 seems to differ from conventional pharmaceutical drugs. Owing to its great efficacy and lack of adverse effects, H2 has promising potential for clinical use against many diseases.", "conclusion": "Since most drugs specifically act to their targets, H2 seems to differ from conventional pharmaceutical drugs. Owing to its great efficacy and lack of adverse effects, H2 has promising potential for clinical use against many diseases." }, { "pmid": "24532027", "year": 2014, "title": "Novel therapeutic strategies for traumatic brain injury: acute antioxidant reinforcement.", "title_en": null, "title_de": "Neuartige therapeutische Strategien für das Schädel-Hirn-Trauma: akute antioxidative Verstärkung.", "journal": "CNS drugs", "authors": "Fernández-Gajardo et al.", "author_search": "fernández-gajardo fernández-gajardo", "doi": "10.1007/s40263-013-0138-y", "doi_url": "https://doi.org/10.1007/s40263-013-0138-y", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/24532027/", "url": "https://h2medicine.org/studies/study-fernandezgajardo-2014-therapeutic-strategies-traumatic-brain/", "methods": [ "saline-iv" ], "indications": [ "neurology", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2014 · Fernández-Gajardo et al. — Novel therapeutic strategies for traumatic brain injury: acute antioxidant reinforcement.", "summary": "This review examines antioxidant-based strategies for treating traumatic brain injury (TBI), including hydrogen-rich saline, arguing that oxidative stress is a central driver of secondary brain damage after trauma. Hydrogen-rich saline appears as one of several candidate antioxidants — alongside mitochondria-targeted compounds, NADPH inhibitors, and polyphenols — in a landscape where no therapy has yet achieved definitive clinical success.", "assessment": "This is a narrative review covering multiple antioxidant strategies for TBI, with hydrogen-rich saline as one entry among many. It provides useful mechanistic context but does not constitute direct evidence for H₂ efficacy in human TBI. Limitations: not a systematic review; no meta-analysis; the field of neuroprotection after TBI has seen many promising preclinical agents fail in clinical trials. H₂ data included are predominantly from animal models.", "abstract": "Traumatic brain injury (TBI) is the most important cause of disability in individuals under the age of 45 years and thus represents a significant social and economic burden. Evidence strongly suggests that oxidative stress is a cornerstone event leading to and propagating secondary injury mechanisms such as excitotoxicity, mitochondrial dysfunction, apoptosis, autophagy, brain edema, and inflammation. TBI has defied conventional approaches to diagnosis and therapy development because of its heterogeneity and complexity. Therefore, it is necessary to explore alternative approaches to therapy development for TBI. The aim of this review is to present a therapeutic approach for TBI, taking into account the evidence supporting the role for oxidative stress in the pathophysiological processes of secondary brain injury. The role of agents such as mitochondria-targeted antioxidants (melatonin and new mitochondria-targeted antioxidants), nicotinamide adenine dinucleotide phosphate (NADPH) inhibitors (antioxidant vitamins and apocynin), and other compounds having mainly antioxidant properties (hydrogen-rich saline, sulforaphane, U-83836E, omega-3, and polyphenols) is covered. The rationale for innovative antioxidant therapies based on current knowledge and particularly the most recent studies regarding this field is discussed. Particular considerations and translational potential of new TBI treatments are examined and a novel therapeutic proposal for TBI is presented.", "conclusion": "The rationale for innovative antioxidant therapies based on current knowledge and particularly the most recent studies regarding this field is discussed. Particular considerations and translational potential of new TBI treatments are examined and a novel therapeutic proposal for TBI is presented." }, { "pmid": "25378931", "year": 2014, "title": "Consumption of water containing over 3.5 mg of dissolved hydrogen could improve vascular endothelial function.", "title_en": null, "title_de": "Der Konsum von Wasser mit mehr als 3,5 mg gelöstem Wasserstoff könnte die vaskuläre Endothelfunktion verbessern.", "journal": "Vascular health and risk management", "authors": "Sakai et al.", "author_search": "sakai sakai", "doi": "10.2147/vhrm.s68844", "doi_url": "https://doi.org/10.2147/vhrm.s68844", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/25378931/", "url": "https://h2medicine.org/studies/study-sakai-2014-consumption-containing-over-dissolved/", "methods": [ "drinking-hrw" ], "indications": [ "cardiovascular", "oxidative-stress" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2014 · Sakai et al. — Consumption of water containing over 3.5 mg of dissolved hydrogen could improve vascular endothelial function.", "summary": "Drinking high-concentration hydrogen-rich water (7 ppm, 3.5 mg H₂ per 500 mL) significantly improved flow-mediated dilation (FMD) of the brachial artery compared to placebo. The randomized crossover study suggests H₂ may protect blood vessel walls from harmful reactive oxygen species — particularly the hydroxyl radical — by preserving nitric oxide signaling. (Vascular Health and Risk Management, 2014.)", "assessment": "A small but methodologically solid pilot study with a meaningful objective endpoint (FMD ultrasound). The result is positive and statistically significant, but the sample size (n=16/18) limits generalisability. The acute single-drink design means long-term cardiovascular effects cannot be inferred. The required threshold of >3.5 mg H₂ per serving is an important practical note — many commercial products fall below this level. Limitations: small n, single acute dose, no follow-up, brachial FMD as a surrogate (not a clinical event endpoint).", "abstract": "BACKGROUND: The redox imbalance between nitric oxide and superoxide generated in the endothelium is thought to play a pivotal role in the development of endothelial dysfunction. A third reactive oxygen species (ROS), H2O2, is known to have both beneficial and detrimental effects on the vasculature. Nonetheless, the influence of the hydroxyl radical, a byproduct of H2O2 decay, is unclear, and there is no direct evidence that the hydroxyl radical impairs endothelial function in conduit arteries. Molecular hydrogen (H2) neutralizes detrimental ROS, especially the hydroxyl radical. OBJECTIVES: To assess the influence of the hydroxyl radical on the endothelium and to confirm that a gaseous antioxidant, H2, can be a useful modulator of blood vessel function. METHODS: The efficacy of water containing a high concentration of H2 was tested by measuring flow-mediated dilation (FMD) of the brachial artery (BA). The subjects were randomly divided into two groups: the high-H2 group, who drank high-H2 water containing 7 ppm H2 (3.5 mg H2 in 500 mL water); and the placebo group. Endothelial function was evaluated by measuring the FMD of the BA. After measurement of diameter of the BA and FMD at baseline, volunteers drank the high-H2 water or placebo water immediately and with a 30-minute interval; FMD was compared to baseline. RESULTS: FMD increased in the high-H2 group (eight males; eight females) from 6.80%±1.96% to 7.64%±1.68% (mean ± standard deviation) and decreased from 8.07%±2.41% to 6.87%±2.94% in the placebo group (ten males; eight females). The ratio to the baseline in the changes of FMD showed significant improvement (P<0.05) in the high-H2 group compared to the placebo group. CONCLUSION: H2 may protect the vasculature from shear stress-derived detrimental ROS, such as the hydroxyl radical, by maintaining the nitric oxide-mediated vasomotor response.", "conclusion": "H2 may protect the vasculature from shear stress-derived detrimental ROS, such as the hydroxyl radical, by maintaining the nitric oxide-mediated vasomotor response." }, { "pmid": "25295663", "year": 2014, "title": "Effectiveness of oral and topical hydrogen for sports-related soft tissue injuries.", "title_en": null, "title_de": "Wirksamkeit von oralem und topischem Wasserstoff bei sportbedingten Weichteilverletzungen.", "journal": "Postgraduate medicine", "authors": "Ostojic et al.", "author_search": "ostojic ostojic", "doi": "10.3810/pgm.2014.09.2813", "doi_url": "https://doi.org/10.3810/pgm.2014.09.2813", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/25295663/", "url": "https://h2medicine.org/studies/study-ostojic-2014-oral-topical-sports-related/", "methods": [ "tablets", "bath-topical", "drinking-hrw" ], "indications": [ "sports-exercise", "joints-rheumatology", "immune-system", "oxidative-stress" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2014 · Ostojic et al. — Effectiveness of oral and topical hydrogen for sports-related soft tissue injuries.", "summary": "In male professional athletes with acute soft tissue injuries, adding oral hydrogen tablets (2 g/day) plus topical hydrogen-rich packs accelerated joint range-of-motion recovery and reduced plasma viscosity compared to standard treatment alone. This single-blind pilot RCT (n=36) suggests H₂ may be a useful adjunct in sports injury management. (Postgraduate Medicine, 2014.)", "assessment": "A promising pilot study with a registered protocol and a clinically relevant population. The positive results for range-of-motion recovery are notable, but must be interpreted cautiously: single-blind design (patients knew their group), only n=12 per arm, exclusively male professional athletes (limiting generalisability to recreational athletes or women), and no long-term follow-up beyond 14 days. Plasma viscosity, while significant, is not a standard rehabilitation endpoint. The study is best viewed as hypothesis-generating, warranting a properly powered double-blind RCT.", "abstract": "BACKGROUND: Because hydrogen therapy has been found beneficial for the treatment of inflammation, ischemia-reperfusion injury, and oxidative stress in humans, it seems useful to evaluate the effects of exogenously administered hydrogen as an element in the immediate management of sports-related soft tissue injuries. The main aim of this pilot study was to examine the effects of 2-week administration of hydrogen on the biochemical markers of inflammation and functional recovery in male professional athletes after acute soft tissue injury. METHOD: During the 2013 season (from March to May), 36 professional athletes were recruited as participants and examined by a certified sports medicine specialist in the first 24 hours after an injury was sustained. Subjects were allocated to 3 randomly assigned trials in a single-blind design. Those in the control group received a traditional treatment protocol for soft tissue injury. Subjects in the first experimental group followed the same procedures as the control group but with additional administration throughout the study of oral hydrogen-rich tablets (2 g per day). Subjects in the second experimental group also followed the procedures of the control group, with additional administration throughout the study of both oral hydrogen-rich tablets (2 g per day) and topical hydrogen-rich packs (6 times per day for 20 minutes). Participants were evaluated at the time of the injury report and at 7 and 14 days after baseline testing. RESULTS: Oral and topical hydrogen intervention was found to augment plasma viscosity decrease as compared with the control group (P = 0.04). Differences were found for range-of-motion recovery between the 3 groups; oral and topical hydrogen intervention resulted in a faster return to normal joint range of motion for both flexion and extension of the injured limb as compared with the control intervention (P < 0.05). CONCLUSION: These preliminary results support the hypothesis that the addition of hydrogen to traditional treatment protocols is potentially effective in the treatment of soft tissue injuries in male professional athletes. Trial identification: Clinicaltrials.gov number NCT01759498.", "conclusion": "These preliminary results support the hypothesis that the addition of hydrogen to traditional treatment protocols is potentially effective in the treatment of soft tissue injuries in male professional athletes. Trial identification: Clinicaltrials.gov number NCT01759498." }, { "pmid": "25201463", "year": 2014, "title": "Effects of intravenous infusion of hydrogen-rich fluid combined with intra-cisternal infusion of magnesium sulfate in severe aneurysmal subarachnoid hemorrhage: study protocol for a randomized controlled trial.", "title_en": null, "title_de": "Wirkungen der intravenösen Infusion von wasserstoffreicher Flüssigkeit kombiniert mit intrazisternaler Infusion von Magnesiumsulfat bei schwerer aneurysmatischer Subarachnoidalblutung: Studienprotokoll für eine randomisierte kontrollierte Studie.", "journal": "BMC neurology", "authors": "Takeuchi et al.", "author_search": "takeuchi takeuchi", "doi": "10.1186/s12883-014-0176-1", "doi_url": "https://doi.org/10.1186/s12883-014-0176-1", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/25201463/", "url": "https://h2medicine.org/studies/study-takeuchi-2014-intravenous-infusion-fluid-combined/", "methods": [ "saline-iv" ], "indications": [ "neurology", "cardiovascular", "fundamentals-safety" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2014 · Takeuchi et al. — Effects of intravenous hydrogen-rich fluid combined with intra-cisternal magnesium sulfate in severe aneurysmal subarachnoid hemorrhage: study protocol for a randomized controlled trial.", "summary": "This paper describes the registered protocol for a 450-patient RCT testing whether intravenous H₂-rich fluid combined with intra-cisternal magnesium sulfate can prevent cerebral vasospasm and delayed cerebral ischemia after severe subarachnoid hemorrhage. No efficacy results are reported — this is a trial design publication only. (BMC Neurology, 2014.)", "assessment": "Important note: this is a study protocol, not a results paper. No efficacy or safety data are reported. The protocol itself is methodologically sound — large n (450), double-blind, three-arm, multi-center, pre-registered (UMIN000014696), with clinically meaningful endpoints. The rationale for combining H₂ (early brain injury) with intracisternal Mg (vasospasm) is biologically coherent. Whether the trial was completed and what results it produced is not determinable from this publication alone. This counts as evidence of serious clinical interest in H₂ for critical neurological emergencies, but not as proof of efficacy.", "abstract": "BACKGROUND: The failures of recent studies intended to prevent cerebral vasospasm have moved the focus of research into delayed cerebral ischemia away from cerebral artery constriction towards other mechanisms. Recent accumulating evidence has suggested that early brain injury is also involved in the development of delayed cerebral ischemia, and that hydrogen can prevent early brain injury. Therefore, we have established a combination therapy of intravenous hydrogen infusion and intra-cisternal magnesium sulfate infusion for the treatment of both early brain injury and cerebral vasospasm. The present randomized controlled clinical trial is designed to investigate the effects of this novel therapeutic strategy on the occurrence of cerebral vasospasm, delayed cerebral ischemia, and clinical outcomes after high-grade subarachnoid hemorrhage. METHODS: This study is a randomized, double-blind, placebo-controlled design to be conducted in two hospitals. A total of 450 patients with high-grade subarachnoid hemorrhage will be randomized to one of three arms: (i) Mg + H2 group, (ii) Mg group, and (iii) control group. Patients who are assigned to the Mg + H2 group will receive intra-cisternal magnesium sulfate infusion (2.5 mmol/L) at 20 mL/h for 14 days and intravenous hydrogen-rich fluid infusion (200 mL) twice a day for 14 days. Patients who are assigned to the Mg group will receive intra-cisternal magnesium sulfate infusion (2.5 mmol/L) at 20 mL/h for 14 days and intravenous normal glucose-electrolyte solution (200 mL) without added hydrogen twice a day for 14 days. Patients who are assigned to the control group will receive intra-cisternal Ringer solution without magnesium sulfate at 20 mL/h for 14 days and intravenous normal glucose-electrolyte solution (200 mL) without added hydrogen twice a day for 14 days. Primary outcome measures will be occurrence of delayed cerebral ischemia and cerebral vasospasm. Secondary outcome measures will be modified Rankin scale score at 3, 6, and 12 months and biochemical markers. DISCUSSION: The present protocol for a randomized, placebo-controlled study of intravenous hydrogen therapy with intra-cisternal magnesium infusion is expected to establish the efficacy and safety of this therapeutic strategy. TRIAL REGISTRATION UMIN-CTR: UMIN000014696.", "conclusion": "DISCUSSION: The present protocol for a randomized, placebo-controlled study of intravenous hydrogen therapy with intra-cisternal magnesium infusion is expected to establish the efficacy and safety of this therapeutic strategy. TRIAL REGISTRATION UMIN-CTR: UMIN000014696." }, { "pmid": "24929023", "year": 2014, "title": "Therapeutic efficacy of infused molecular hydrogen in saline on rheumatoid arthritis: a randomized, double-blind, placebo-controlled pilot study.", "title_en": null, "title_de": "Therapeutische Wirksamkeit von in Kochsalzlösung infundiertem molekularem Wasserstoff bei rheumatoider Arthritis: eine randomisierte, doppelblinde, placebokontrollierte Pilotstudie.", "journal": "International immunopharmacology", "authors": "Ishibashi et al.", "author_search": "ishibashi ishibashi", "doi": "10.1016/j.intimp.2014.06.001", "doi_url": "https://doi.org/10.1016/j.intimp.2014.06.001", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/24929023/", "url": "https://h2medicine.org/studies/study-ishibashi-2014-therapeutic-infused-saline-rheumatoid/", "methods": [ "saline-iv" ], "indications": [ "cancer", "joints-rheumatology", "immune-system", "oxidative-stress", "fundamentals-safety" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2014 · Ishibashi et al. — Therapeutic efficacy of infused molecular hydrogen in saline on rheumatoid arthritis: a randomized, double-blind, placebo-controlled pilot study.", "summary": "In 24 patients with rheumatoid arthritis (RA), intravenous infusion of H₂-enriched saline (500 mL/day, 5 days) significantly reduced disease activity scores (DAS28), lowered IL-6 and the oxidative damage marker 8-OHdG, and reduced MMP-3 — a marker of joint destruction — after 4 weeks. The double-blind, placebo-controlled design makes this one of the more rigorous early H₂ trials. (International Immunopharmacology, 2014.)", "assessment": "One of the stronger early H₂ clinical trials due to its double-blind, placebo-controlled design and multiple relevant biomarkers. Results are positive and statistically significant for DAS28, IL-6, 8-OHdG, and MMP-3. The null finding for TNF-α is honest and informative, suggesting H₂ does not act as a broad TNF-α inhibitor. Limitations: very small n (12 per arm), short duration (5-day infusion + 4-week follow-up), single-center, no long-term remission data. The study is best interpreted as a proof-of-concept warranting a larger, longer RCT in RA.", "abstract": "The aim of this study was to demonstrate the safety and efficacy of H2-saline infusion for treatment of rheumatoid arthritis (RA). We conducted a randomized, double-blind, placebo-controlled investigation of the infusion of 1 ppm H2-dissolved saline (H2-saline) in 24 RA patients. Patients were randomized 1:1 to receive 500 ml of either H2-saline or placebo-saline, which was drop infused intravenously (DIV) daily for 5 days. The disease activity score in 28 joints (DAS28) was measured at baseline, immediately post infusion, and after 4 weeks. Therapeutic effects of H2-saline on joint inflammation were estimated by measuring serum biomarkers for RA, tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), and urinary 8-hydroxydeoxyguanosine (8-OHdG). In the H2-infused group, average DAS28 decreased from 5.18 ± 1.16 to 4.02 ± 1.25 immediately post infusion and reached 3.74 ± 1.22 after 4 weeks. No significant decrease in DAS28 was observed in the placebo group throughout the study. IL-6 levels in the H2 group significantly decreased in 4 weeks by 37.3 ± 62.0% compared to baseline, whereas it increased by 33.6 ± 34.4% in the placebo group. TNFα levels did not change remarkably in the H2 or placebo groups in 4 weeks post-infusion compared to baseline. The relative ratio of 8-OHdG in the H2 group also significantly decreased by 4.7%. After 4 weeks, MMP3 was significantly reduced by 19.2% ± 24.6% in the H2 group, and increased by 16.9% ± 50.2% in the placebo group. Drop infusion of H2 safely and effectively reduced RA disease activity.", "conclusion": "After 4 weeks, MMP3 was significantly reduced by 19.2% ± 24.6% in the H2 group, and increased by 16.9% ± 50.2% in the placebo group. Drop infusion of H2 safely and effectively reduced RA disease activity." }, { "pmid": "25942929", "year": 2014, "title": "Polymer encapsulation of magnesium to control biodegradability and biocompatibility.", "title_en": null, "title_de": "Polymerverkapselung von Magnesium zur Steuerung von Biologisch-Abbaubarkeit und Biokompatibilität.", "journal": "Journal of nanoscience and nanotechnology", "authors": "Bazaka et al.", "author_search": "bazaka bazaka", "doi": "10.1166/jnn.2014.9409", "doi_url": "https://doi.org/10.1166/jnn.2014.9409", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/25942929/", "url": "https://h2medicine.org/studies/study-bazaka-2014-polymer-encapsulation-magnesium-control/", "methods": [ "inhalation" ], "indications": [ "immune-system" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2014 · Bazaka et al. — Polymer encapsulation of magnesium to control biodegradability and biocompatibility.", "summary": "This animal and cell study investigated plasma-polymerised coatings on biodegradable magnesium implants — where hydrogen gas appears as an unwanted by-product of magnesium corrosion, not as a therapeutic agent. The polymer coating successfully slowed magnesium degradation and improved cell viability compared to uncoated samples.", "assessment": "This is a preclinical material science/animal study. Hydrogen gas is a corrosion by-product here — not a bioactive intervention. The findings are relevant to biodegradable implant engineering but have no bearing on molecular hydrogen as a health supplement or therapy. Results are from in-vitro cell models and rat-tissue simulated body fluid, not from a therapeutic H₂ study.", "abstract": "Clinical utility of biodegradable magnesium implants is undermined by the untimely degradation of these materials in vivo. Their high corrosion rate leads to loss of mechanical integrity, peri-implant alkalization and localised accumulation of hydrogen gas. Biodegradable coatings were produced on pure magnesium using RF plasma polymerisation. A monoterpene alcohol with known anti-inflammatory and antibacterial properties was used as a polymer precursor. The addition of the polymeric layer was found to reduce the degradation rate of magnesium in simulated body fluid. The in vitro studies indicated good cytocompatibility of non-adherent THP-1 cells and mouse macrophage cells with the polymer, and the polymer coated sample. The viability of THP-1 cells was significantly improved when in contact with polymer encapsulated magnesium compared to unmodified samples. Collectively, these results suggest plasma enhanced polymer encapsulation of magnesium as a suitable method to control degradation kinetics of this biomaterial.", "conclusion": "The viability of THP-1 cells was significantly improved when in contact with polymer encapsulated magnesium compared to unmodified samples. Collectively, these results suggest plasma enhanced polymer encapsulation of magnesium as a suitable method to control degradation kinetics of this biomaterial." }, { "pmid": "24890090", "year": 2014, "title": "Thiazolidine-2,4-diones derivatives as PPAR-γ agonists: synthesis, molecular docking, in vitro and in vivo antidiabetic activity with hepatotoxicity risk evaluation and effect on PPAR-γ gene expression.", "title_en": null, "title_de": "Thiazolidin-2,4-dion-Derivate als PPAR-γ-Agonisten: Synthese, molekulares Docking, antidiabetische Aktivität in vitro und in vivo mit Bewertung des Hepatotoxizitätsrisikos.", "journal": "Bioorganic & medicinal chemistry letters", "authors": "Nazreen et al.", "author_search": "nazreen nazreen", "doi": "10.1016/j.bmcl.2014.05.034", "doi_url": "https://doi.org/10.1016/j.bmcl.2014.05.034", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/24890090/", "url": "https://h2medicine.org/studies/study-nazreen-2014-thiazolidine-diones-derivatives-ppar/", "methods": [ "inhalation" ], "indications": [ "diabetes", "liver" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2014 · Nazreen et al. — Thiazolidine-2,4-diones derivatives as PPAR-γ agonists: synthesis, molecular docking, in vitro and in vivo antidiabetic activity with hepatotoxicity risk evaluation.", "summary": "This in-vitro and animal pharmacology study synthesised new thiazolidinedione-chromone compounds as potential antidiabetic agents — using hydrogen gas as a chemical reducing agent in the synthesis process, not as a therapeutic substance. The most active compounds lowered blood glucose comparably to pioglitazone with less hepatotoxic risk.", "assessment": "This is an in-vitro and animal pharmacology/medicinal chemistry study. Hydrogen gas appears only as a synthetic reagent — not as a bioactive substance under investigation. The paper is entirely unrelated to molecular hydrogen therapy or supplementation. Its findings are relevant to antidiabetic drug development, not to H₂ medicine.", "abstract": "A library of conjugates of chromones and 2,4-thiazolidinedione has been synthesized by Knoevenagel condensation followed by reduction using hydrogen gas and Pd/C as a catalyst. Compounds 5c and 5e were most effective in lowering the blood glucose level comparable to standard drug pioglitazone. Compound 5e exhibited potent PPAR-γ transactivation of 48.72% in comparison to pioglitazone (62.48%). All the molecules showed good glide score against the PPAR-γ target in molecular docking study. PPAR-γ gene expression was significantly increased by compound 5e (2.56-fold) in comparison to standard drug pioglitazone. Compounds 5e and 5c did not cause any damage to the liver and may be considered as promising candidates for the development of new antidiabetic agents.", "conclusion": "PPAR-γ gene expression was significantly increased by compound 5e (2.56-fold) in comparison to standard drug pioglitazone. Compounds 5e and 5c did not cause any damage to the liver and may be considered as promising candidates for the development of new antidiabetic agents." }, { "pmid": "24793096", "year": 2014, "title": "Effect of hydrogen-rich water on acute peritonitis of rat models.", "title_en": null, "title_de": "Wirkung von wasserstoffreichem Wasser auf akute Peritonitis in Rattenmodellen.", "journal": "International immunopharmacology", "authors": "Zhang et al.", "author_search": "zhang zhang", "doi": "10.1016/j.intimp.2014.04.011", "doi_url": "https://doi.org/10.1016/j.intimp.2014.04.011", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/24793096/", "url": "https://h2medicine.org/studies/study-zhang-2014-acute-peritonitis-rat-models/", "methods": [ "saline-iv", "drinking-hrw" ], "indications": [ "cancer", "immune-system" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2014 · Zhang et al. — Effect of hydrogen-rich water on acute peritonitis of rat models.", "summary": "This animal study tested hydrogen-rich water (HRW) in three different rat models of acute peritonitis and found consistent protective effects: lower inflammatory markers, reduced oxidative damage, and decreased NF-κB expression in peritoneal tissue. The results support a role for H₂ as an anti-inflammatory and antioxidant agent in peritoneal infection — but entirely in rats, not humans.", "assessment": "This is a preclinical animal study (rats) with methodological strength (three parallel models) but no human data. The consistent findings across different peritonitis induction methods are encouraging for the hypothesis that H₂ modulates inflammation. Limitations: all male Sprague-Dawley rats; mechanism (NF-κB reduction) is correlational; the anti-bacterial effect claim is unsubstantiated by direct microbiological data in the abstract. Results cannot be directly applied to human peritonitis treatment.", "abstract": "OBJECTIVE: To study the effect of hydrogen-rich water (HRW) on acute peritonitis with three different rat models. METHODS: Acute peritonitis was induced by three methods including intraperitoneal injection of lipopolysaccharide (LPS), rats' feces or cecal ligation and puncture (CLP) operation. For each model, male Sprague Dawley rats were used and distributed into saline control group, HRW control group, saline plus model group, and HRW plus model group. Saline or HRW (3 ml per rat) was orally administered by gavage for 7 days beforehand and 3 days after modeling. The efficacy was tested by detecting concentrations of white blood cells (WBCs), plasma endotoxin, interleukin (IL)-6 and tumor necrosis factor (TNF)-α. The activities of malondialdehyde (MDA), myeloperoxidase (MPO) and glutathione (GSH) in visceral peritoneum tissues were also evaluated. Meanwhile, histopathology examination of visceral peritoneum was performed using hematoxylin and eosin staining. The expression and location of nuclear factor kappaB (NF-κB) in the visceral peritoneum were detected by immunohistochemistry. RESULTS: Three models showed the same result that hydrogen-rich water had an efficient protective effect on acute peritonitis. HRW could significantly lower the levels of WBCs, plasma endotoxin and cytokines, enhance GSH activity and reduce MPO and MDA activities in the peritoneum tissue when compared with that of groups with only saline treated. Simultaneously, we found that HRW could also decrease the NF-κB expression in the peritoneum tissues. CONCLUSION: Hydrogen-rich water could alleviate the severity of acute peritonitis, and it might perform this function by its anti-inflammation, anti-oxidation and anti-bacterial effects and reducing NF-κB expression in the peritoneum tissues.", "conclusion": "Hydrogen-rich water could alleviate the severity of acute peritonitis, and it might perform this function by its anti-inflammation, anti-oxidation and anti-bacterial effects and reducing NF-κB expression in the peritoneum tissues." }, { "pmid": "24694477", "year": 2014, "title": "Do alpha-glucosidase inhibitors have the potential to induce portal venous gas? -Two clinical case reports.", "title_en": null, "title_de": "Können Alpha-Glucosidase-Hemmer portalvenöses Gas induzieren? – Zwei klinische Fallberichte.", "journal": "Internal medicine (Tokyo, Japan)", "authors": "Makiyama et al.", "author_search": "makiyama makiyama", "doi": "10.2169/internalmedicine.53.1789", "doi_url": "https://doi.org/10.2169/internalmedicine.53.1789", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/24694477/", "url": "https://h2medicine.org/studies/study-makiyama-2014-alpha-glucosidase-inhibitors-have/", "methods": [], "indications": [ "diabetes" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "byproduct", "headline": "2014 · Makiyama et al. — Do alpha-glucosidase inhibitors have the potential to induce portal venous gas? — Two clinical case reports.", "summary": "This case report describes two diabetic patients who developed portal venous gas after starting alpha-glucosidase inhibitor (α-GI) therapy. The authors propose that α-GI drugs increase intestinal gas pressure — including H₂ gas produced by gut fermentation — which may cause pneumatosis cystoides intestinalis or portal venous gas. Important: H₂ here is a gut fermentation byproduct, not a therapeutic intervention. (Internal Medicine, 2014.)", "assessment": "This is not a therapeutic H₂ study. H₂ in this paper is an unwanted endogenous byproduct of drug-induced gut fermentation, not an administered therapeutic agent. The paper is a case report (n=2), the lowest level of clinical evidence. Its relevance to the H₂ medicine field is limited to: (1) illustrating that H₂ is indeed produced in the human gut, and (2) documenting that extreme gas accumulation can have rare adverse effects. It should not be cited as evidence for or against therapeutic H₂. Evidence level is very low by design.", "abstract": "We herein report two cases of portal venous gas (PVG) following alpha-glucosidase inhibitor (α-GI) therapy for diabetes mellitus. Anti-diabetic treatment with voglibose was commenced in the first case, while the second case was treated with miglitol. Both patients recovered without intensive treatment after discontinuing the α-GI therapy. α-GI medications may increase internal intestinal tract pressure by releasing carbon dioxide and hydrogen gas, potentially causing pneumatosis cystoides intestinalis (PCI) or PVG. Our experience suggests that α-GI therapy is an important potential cause of portal venous gas that can be treated conservatively.", "conclusion": "α-GI medications may increase internal intestinal tract pressure by releasing carbon dioxide and hydrogen gas, potentially causing pneumatosis cystoides intestinalis (PCI) or PVG. Our experience suggests that α-GI therapy is an important potential cause of portal venous gas that can be treated conservatively." }, { "pmid": "24529916", "year": 2014, "title": "Parkinson's disease may be due to failure of melanin in the Substantia Nigra to produce molecular hydrogen from dissociation of water, to protect the brain from oxidative stress.", "title_en": null, "title_de": "Die Parkinson-Krankheit könnte auf das Versagen von Melanin in der Substantia nigra zurückzuführen sein, molekularen Wasserstoff aus der Dissoziation von Wasser zu produzieren.", "journal": "Medical hypotheses", "authors": "Brenner", "author_search": "brenner brenner", "doi": "10.1016/j.mehy.2014.01.013", "doi_url": "https://doi.org/10.1016/j.mehy.2014.01.013", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/24529916/", "url": "https://h2medicine.org/studies/study-brenner-2014-parkinson-disease-may-due/", "methods": [ "drinking-hrw" ], "indications": [ "neurology", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2014 · Brenner — Parkinson's disease may be due to failure of melanin in the Substantia Nigra to produce molecular hydrogen from dissociation of water.", "summary": "This is a speculative theoretical paper proposing that melanin in the brain's Substantia Nigra normally splits water into molecular hydrogen and oxygen — and that the loss of this capacity may underlie Parkinson's disease. The hypothesis is unproven and has not been experimentally validated, but it raises an interesting mechanistic question about endogenous H₂ production.", "assessment": "This is a pure theoretical hypothesis paper — no experimental data are presented or reviewed. The proposed mechanism (neuromelanin as a water-splitting H₂ generator) is creative but unvalidated. It should be read as early-stage speculation. The idea that supplemental H₂ might compensate for any such deficit is biologically plausible in principle, but this paper provides no evidence of efficacy or safety in Parkinson's disease. Human clinical data are entirely absent.", "abstract": "Melanin, a hybrid electronic/ionic conductor may have the potential to split the water molecule into molecular hydrogen and molecular oxygen. Molecular hydrogen is an antioxidant and may be instrumental in preventing the excessive oxidation leading to Parkinson's disease. Melanin, located in the Substantia Nigra, deteriorates in Parkinson's disease so may be related to the development and progression of the disease, since molecular hydrogen would no longer be generated as it deteriorates. Environmental toxins, thought to be related to development of Parkinson's disease, may cause deterioration of intrinsic melanin, since it is a chelator which would collect such environmental contaminants, but its function of splitting the water molecule into molecular hydrogen and oxygen could be effected as a consequence. Restoring melanin function or providing supplemental molecular hydrogen might be potential treatments for Parkinson's disease.", "conclusion": "Environmental toxins, thought to be related to development of Parkinson's disease, may cause deterioration of intrinsic melanin, since it is a chelator which would collect such environmental contaminants, but its function of splitting the water molecule into molecular hydrogen and oxygen could be effected as a consequence. Restoring melanin function or providing supplemental molecular hydrogen mig" }, { "pmid": "24509162", "year": 2014, "title": "Maternal molecular hydrogen administration ameliorates rat fetal hippocampal damage caused by in utero ischemia-reperfusion.", "title_en": null, "title_de": "Mütterliche Verabreichung von molekularem Wasserstoff lindert den durch intrauterine Ischämie-Reperfusion verursachten Schaden am fetalen Hippocampus der Ratte.", "journal": "Free radical biology & medicine", "authors": "Mano et al.", "author_search": "mano mano", "doi": "10.1016/j.freeradbiomed.2014.01.037", "doi_url": "https://doi.org/10.1016/j.freeradbiomed.2014.01.037", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/24509162/", "url": "https://h2medicine.org/studies/study-mano-2014-maternal-administration-ameliorates-rat/", "methods": [ "drinking-hrw" ], "indications": [ "liver", "neurology", "cardiovascular", "womens-health", "pregnancy", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2014 · Mano et al. — Maternal molecular hydrogen administration ameliorates rat fetal hippocampal damage caused by in utero ischemia-reperfusion.", "summary": "In this rat study, pregnant mothers that drank hydrogen-saturated water passed measurable H₂ to the placenta, which protected fetal hippocampal neurons from ischemia-reperfusion injury — and improved the learning and memory of the offspring at 8 weeks of age. These are promising neuroprotective findings in an animal model of pregnancy-related brain injury, but no human data exist.", "assessment": "This is a well-designed preclinical animal study with an unusually strong functional endpoint (Morris water maze at 8 weeks), but all work is in rats. The demonstration of transplacental H₂ transfer and offspring cognitive protection is scientifically noteworthy. Limitations: surgically induced ischemia is an extreme model; the rat placenta differs structurally from the human placenta; no safety data on H₂ consumption during human pregnancy are available. Results cannot be applied to human obstetric practice.", "abstract": "Molecular hydrogen (H2) scavenges hydroxyl radicals. Recently, H2 has been reported to prevent a variety of diseases associated with oxidative stress in model systems and in humans. Here, we studied the effects of H2 on rat fetal hippocampal damage caused by ischemia and reperfusion (IR) on day 16 of pregnancy with the transient occlusion of the bilateral utero-ovarian arteries. Starting 2 days before the operation, we provided the mothers with hydrogen-saturated water ad libitum until vaginal delivery. We observed a significant increase in the concentration of H2 in the placenta after the oral administration of hydrogen-saturated water to the mothers, with less placental oxidative damage after IR in the presence of H2. Neonatal growth retardation was observed in the IR group, which was alleviated by the H2 administration. We analyzed the neuronal cell damage in the CA1 and CA3 areas of the hippocampus at day 7 after birth by immunohistochemical analysis of the 8-oxo-7,8-dihydro-2׳-deoxyguanosine- and 4-hydroxy-2-nonenal-modified proteins. Both oxidative stress markers were significantly increased in the IR group, which was again ameliorated by the H2 intake. Last, 8-week-old rats were subjected to a Morris water maze test. Maternal H2 administration improved the reference memory of the offspring to the sham level after IR injury during pregnancy. Overall, the present results support the idea that maternal H2 intake helps prevent the hippocampal impairment of offspring induced by IR during pregnancy.", "conclusion": "Maternal H2 administration improved the reference memory of the offspring to the sham level after IR injury during pregnancy. Overall, the present results support the idea that maternal H2 intake helps prevent the hippocampal impairment of offspring induced by IR during pregnancy." }, { "pmid": "24491676", "year": 2014, "title": "Clusianone, a naturally occurring nemorosone regioisomer, uncouples rat liver mitochondria and induces HepG2 cell death.", "title_en": null, "title_de": "Clusianon, ein natürlich vorkommendes Nemoroson-Regioisomer, entkoppelt Rattenleber-Mitochondrien und induziert den Zelltod von HepG2-Zellen.", "journal": "Chemico-biological interactions", "authors": "Reis et al.", "author_search": "reis reis", "doi": "10.1016/j.cbi.2014.01.015", "doi_url": "https://doi.org/10.1016/j.cbi.2014.01.015", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/24491676/", "url": "https://h2medicine.org/studies/study-reis-2014-clusianone-naturally-occurring-nemorosone/", "methods": [ "unspecified" ], "indications": [ "liver", "cancer" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2014 · Reis et al. — Clusianone, a naturally occurring nemorosone regioisomer, uncouples rat liver mitochondria and induces HepG2 cell death.", "summary": "This in-vitro and animal study characterised clusianone — a natural plant compound — as a mitochondrial uncoupler and anticancer agent, where hydrogen appears only as a structural feature of the molecule (an intramolecular hydrogen bond), not as a therapeutic substance. The compound showed cytotoxic effects against liver cancer cells (HepG2) but weaker than its structural relative nemorosone.", "assessment": "This paper has no relevance to molecular hydrogen (H₂) medicine. The word ‚hydrogen' refers to a chemical bond within a plant-derived molecule, not to H₂ gas or hydrogen-rich water. It is an in-vitro/animal natural product pharmacology study. There are no H₂ therapeutic endpoints, no consumption of H₂, and no findings applicable to hydrogen medicine.", "abstract": "Clusianone is a member of the polycyclic polyprenylated acylphloroglucinol family of natural products; its cytotoxic mechanism is unknown. Clusianone is a structural isomer of nemorosone, which is a mitochondrial uncoupler and a well-known cytotoxic anti-cancer agent; thus, we addressed clusianone action at the mitochondria and its potential cytotoxic effects on cancer cells. In the HepG2 hepatocarcinoma cell line, clusianone induced mitochondrial membrane potential dissipation, ATP depletion and phosphatidyl serine externalization; this later event is indicative of apoptosis induction. In isolated mitochondria from rat liver, clusianone promoted protonophoric mitochondrial uncoupling. This was evidenced by the dissipation of mitochondrial membrane potential, an increase in resting respiration, an inhibition of Ca(2+) influx, stimulation of Ca(2+) efflux in Ca(2+)-loaded mitochondria, a decrease in ATP and NAD(P)H levels, generation of ROS, and swelling of valinomycin-treated organelles in hyposmotic potassium acetate media. The cytotoxic and uncoupling actions of clusianone were appreciably less than those of nemorosone, likely due to the presence of an intra-molecular hydrogen bond with the juxtaposed carbonyl group at the C15 position. Therefore, clusianone is capable of pharmacologically increasing the leakage of protons from the mitochondria and with favorable cytotoxicity in relation to nemorosone.", "conclusion": "The cytotoxic and uncoupling actions of clusianone were appreciably less than those of nemorosone, likely due to the presence of an intra-molecular hydrogen bond with the juxtaposed carbonyl group at the C15 position. Therefore, clusianone is capable of pharmacologically increasing the leakage of protons from the mitochondria and with favorable cytotoxicity in relation to nemorosone." }, { "pmid": "24392771", "year": 2014, "title": "Hydrogen-rich water affected blood alkalinity in physically active men.", "title_en": null, "title_de": "Wasserstoffreiches Wasser beeinflusste die Blutalkalität bei körperlich aktiven Männern.", "journal": "Research in sports medicine (Print)", "authors": "Ostojic et al.", "author_search": "ostojic ostojic", "doi": "10.1080/15438627.2013.852092", "doi_url": "https://doi.org/10.1080/15438627.2013.852092", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/24392771/", "url": "https://h2medicine.org/studies/study-ostojic-2014-affected-blood-alkalinity-physically/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise", "cardiovascular" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2014 · Ostojic et al. — Hydrogen-rich water affected blood alkalinity in physically active men.", "summary": "Drinking 2 L of hydrogen-rich water (HRW) daily for 14 days significantly raised both resting and post-exercise arterial blood pH, and elevated fasting bicarbonate levels, in 52 healthy physically active men — without any reported side effects. This randomized, double-blind, placebo-controlled trial points to a potential alkalizing effect of HRW relevant to exercise-induced acidosis. (Research in Sports Medicine, 2014.)", "assessment": "A well-designed, adequately powered study with objective arterial blood gas measurements. Results are statistically significant and internally consistent. The effect sizes are small (ΔpH ≈ 0.04–0.07), and whether they translate into measurable performance benefits was not tested here. The mechanism (is it the H₂ itself, or the water's mineral content?) is not isolated. Limitations: all-male, young, physically active population only; alkalizing mechanism not mechanistically confirmed; no performance outcome tested; arterial blood sampling is invasive and limits real-world applicability of the findings.", "abstract": "Possible appliance of effective and safe alkalizing agent in the treatment of metabolic acidosis could be of particular interest to humans experiencing an increase in plasma acidity, such as exercise-induced acidosis. In the present study we tested the hypothesis that the daily oral intake of 2L of hydrogen-rich water (HRW) for 14 days would increase arterial blood alkalinity at baseline and post-exercise as compared with the placebo. This study was a randomized, double blind, placebo-controlled trial involving 52 presumably healthy physically active male volunteers. Twenty-six participants received HRW and 26 a placebo (tap water) for 14 days. Arterial blood pH, partial pressure for carbon dioxide (pCO2), and bicarbonates were measured at baseline and postexercise at the start (day 0) and at the end of the intervention period (day 14). Intake of HRW significantly increased fasting arterial blood pH by 0.04 (95% confidence interval; 0.01 - 0.08; p < 0.001), and postexercise pH by 0.07 (95% confidence interval; 0.01 - 0.10; p = 0.03) after 14 days of intervention. Fasting bicarbonates were significantly higher in the HRW trial after the administration regimen as compared with the preadministration (30.5 ± 1.9 mEq/L vs. 28.3 ± 2.3 mEq/L; p < 0.0001). No volunteers withdrew before the end of the study, and no participant reported any vexatious side effects of supplementation. These results support the hypothesis that HRW administration is safe and may have an alkalizing effect in young physically active men.", "conclusion": "No volunteers withdrew before the end of the study, and no participant reported any vexatious side effects of supplementation. These results support the hypothesis that HRW administration is safe and may have an alkalizing effect in young physically active men." }, { "pmid": "24291328", "year": 2014, "title": "Controlling initial biodegradation of magnesium by a biocompatible strontium phosphate conversion coating.", "title_en": null, "title_de": "Steuerung der initialen Biodegradation von Magnesium durch eine biokompatible Strontiumphosphat-Konversionsbeschichtung", "journal": "Acta biomaterialia", "authors": "Chen et al.", "author_search": "chen chen", "doi": "10.1016/j.actbio.2013.11.016", "doi_url": "https://doi.org/10.1016/j.actbio.2013.11.016", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/24291328/", "url": "https://h2medicine.org/studies/study-chen-2014-controlling-initial-biodegradation-magnesium/", "methods": [ "inhalation", "bath-topical" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2014 · Chen — Controlling initial biodegradation of magnesium by a biocompatible strontium phosphate conversion coating", "summary": "Magnesium implants dissolve too quickly after implantation — a strontium phosphate (SrP) coating developed in this in-vitro study significantly slows this degradation. A side effect of Mg degradation is hydrogen gas evolution; the coating suppresses this as well. The cells (human mesenchymal stem cells) tolerated the coated implants without impairment of proliferation or differentiation. (Acta Biomaterialia, 2014.)", "assessment": "This is a preclinical materials study with no relevance to therapeutic molecular hydrogen. The hydrogen mentioned is unwanted corrosion gas from magnesium implants, which the coating is designed to suppress. The study itself is solid cell-biology and surface-chemistry work, but it does not provide any evidence — positive or negative — for H₂ as a health intervention. It is indexed here due to the keyword „hydrogen gas evolution.“ No human evidence, no therapeutic H₂ application.", "abstract": "A simple strontium phosphate (SrP) conversion coating process was developed to protect magnesium (Mg) from the initial degradation post-implantation. The coating morphology, deposition rate and resultant phases are all dependent on the processing temperature, which determines the protective ability for Mg in minimum essential medium (MEM). Coatings produced at 80 °C are primarily made up of strontium apatite (SrAp) with a granular surface, a high degree of crystallinity and the highest protective ability, which arises from retarding anodic dissolution of Mg in MEM. Following 14 days' immersion in MEM, the SrAp coating maintained its integrity with only a small fraction of the surface corroded. The post-degradation effect of uncoated Mg and Mg coated at 40 and 80 °C on the proliferation and differentiation of human mesenchymal stem cells was also studied, revealing that the SrP coatings are biocompatible and permit proliferation to a level similar to that of pure Mg. The present study suggests that the SrP conversion coating is a promising option for controlling the early rapid degradation rate, and hence hydrogen gas evolution, of Mg implants without adverse effects on surrounding cells and tissues.", "conclusion": "The post-degradation effect of uncoated Mg and Mg coated at 40 and 80 °C on the proliferation and differentiation of human mesenchymal stem cells was also studied, revealing that the SrP coatings are biocompatible and permit proliferation to a level similar to that of pure Mg. The present study suggests that the SrP conversion coating is a promising option for controlling the early rapid degradati" }, { "pmid": "24068473", "year": 2014, "title": "DNA-binding studies and antitumor evaluation of novel water soluble organic pip and hpip analogs.", "title_en": null, "title_de": "DNA-Bindungsstudien und Antitumor-Bewertung neuartiger wasserlöslicher organischer pip- und hpip-Analoga", "journal": "Applied biochemistry and biotechnology", "authors": "Coban et al.", "author_search": "coban coban", "doi": "10.1007/s12010-013-0513-7", "doi_url": "https://doi.org/10.1007/s12010-013-0513-7", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/24068473/", "url": "https://h2medicine.org/studies/study-coban-2014-dna-binding-antitumor-soluble/", "methods": [ "unspecified" ], "indications": [ "cancer" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2014 · Coban — DNA-binding studies and antitumor evaluation of novel water soluble organic pip and hpip analogs", "summary": "Two newly synthesized water-soluble organic compounds (pip and hpip analogs) were tested for DNA-binding and antitumor activity in cell culture. Both compounds bind strongly to DNA via electrostatic and intercalative modes, inhibit DNA transcription, and show cytotoxic activity against cancer cells. The hydrogen mentioned in this study refers to intramolecular hydrogen bonding within the compounds — not to therapeutic molecular hydrogen (H₂). (Applied Biochemistry and Biotechnology, 2014.)", "assessment": "This is a preclinical in-vitro chemistry study on novel organic antitumor compounds. It has no connection to therapeutic molecular hydrogen (H₂). The hydrogen referenced is intramolecular hydrogen bonding — a basic chemical structural feature, not the dissolved gas H₂ studied in hydrogen medicine. This entry appears in the H₂ database due to keyword matching. No conclusions about H₂ therapy can be drawn from this paper.", "abstract": "Two new water-soluble pip and hpip analogs, 1 and 2 pip = 2-phenylimidazo[4,5-f][1, 10]phenanthroline; hpip = 2-(2-hydroxyphenyl)imidazo[4,5-f][1, 10]phenanthroline, have been synthesized and fully characterized by CHN analysis, MALDI-TOF MS, (1)H-NMR, IR (ATR), and UV-Vis methods. The DNA-binding behaviors of both compounds have been studied by viscosity measurements, spectroscopic methods, and gel electrophoresis studies, and potential for antitumor activity was evaluated by measuring their ability to inhibit DNA transcription. The results indicate that both compounds show some strong binding to DNA in a mixture of electrostatic and intercalative mode resulting in the intrinsic binding constants Kb of (4.0 ± 0.5) × 10(5) M(-1) and (7.5 ± 0.5) × 10(5) M(-1) for 1 and 2, respectively. These strong binding affinities for DNA are comparable for that seen for many transition metal-based intercalators. Comparatively, observed difference in the DNA-binding affinities of two complexes can be reasonably explained by the presence of an intra-molecular hydrogen-bonding between the ortho-phenolic group and the nitrogen atom of the imidazole ring. The extended co-planarity of 2 due to the intramolecular hydrogen bonding may lead to an enhancement of DNA binding affinity of 2. In addition, 2 can promote cleavage of pBR322 DNA upon irradiation, it inhibits DNA transcription and it is more cytotoxic at lower concentrations in comparison to 1, as revealed by the spectroscopic measurements.", "conclusion": "The extended co-planarity of 2 due to the intramolecular hydrogen bonding may lead to an enhancement of DNA binding affinity of 2. In addition, 2 can promote cleavage of pBR322 DNA upon irradiation, it inhibits DNA transcription and it is more cytotoxic at lower concentrations in comparison to 1, as revealed by the spectroscopic measurements." }, { "pmid": "24697097", "year": 2013, "title": "[Equol: a metabolite of soy isoflavones by intestinal microflora--a review].", "title_en": null, "title_de": "Equol: ein Metabolit von Soja-Isoflavonen durch die Darmflora — eine Übersichtsarbeit", "journal": "Wei sheng wu xue bao = Acta microbiologica Sinica", "authors": "Zheng et al.", "author_search": "zheng zheng", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/24697097/", "url": "https://h2medicine.org/studies/study-zheng-2013-equol-metabolite-soy-isoflavones/", "methods": [ "inhalation" ], "indications": [ "fundamentals-safety" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2013 · Zheng — Equol: a metabolite of soy isoflavones by intestinal microflora — a review", "summary": "Equol, a metabolite of the soy isoflavone daidzein produced by gut bacteria, may explain the health benefits of soy — but only 33–50 % of humans can produce it. This review summarizes the mechanisms of equol formation, its bioavailability, influencing factors, and — notably — the emerging role of hydrogen gas in microbial equol production by the gut microbiome. (Acta Microbiologica Sinica, 2013.)", "assessment": "This is a review article summarizing existing literature on equol and gut microbiota, with a preliminary note on the role of H₂ in microbial metabolism. It provides no original experimental data. The H₂–equol connection cited was at a very early research stage (2013) and has limited direct clinical relevance. No conclusions about therapeutic H₂ administration can be drawn from this review. The honest reading is: H₂ produced by gut bacteria may influence equol-producing microbial ecology — an interesting microbiome hypothesis, not a therapeutic claim.", "abstract": "Equol, a microbial metabolite of daidzein, has been hypothesized as clue to the effectiveness of soy and its isoflavones but only 33% - 50% of human population can excrete equol. Recently studies indicated that hydrogen gas playsan important role in equol formation. However, researches focus on this area are just started. In this paper, the corresponding research results of previous studies have been reviewed, including the underlying mechanism of equol formation and bioavailability, factors influencing equol production and the role of hydrogen gas on microbial equol formation.", "conclusion": "However, researches focus on this area are just started. In this paper, the corresponding research results of previous studies have been reviewed, including the underlying mechanism of equol formation and bioavailability, factors influencing equol production and the role of hydrogen gas on microbial equol formation." }, { "pmid": "24358804", "year": 2013, "title": "[Introspection of oxidant/antioxidant imbalance in the inner ear].", "title_en": null, "title_de": "Betrachtung des Oxidantien-/Antioxidantien-Ungleichgewichts im Innenohr", "journal": "Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery", "authors": "Wang et al.", "author_search": "wang wang", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/24358804/", "url": "https://h2medicine.org/studies/study-wang-2013-introspection-oxidant-antioxidant-imbalance/", "methods": [ "unspecified" ], "indications": [ "skin-aging", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2013 · Wang — Introspection of oxidant/antioxidant imbalance in the inner ear", "summary": "Free radicals play a central role in inner ear damage from noise, ototoxic drugs, and aging — but antioxidant therapy without knowledge of the specific oxidative stress type risks further harm. This review introduces molecular hydrogen as a selective antioxidant that neutralizes only the most harmful reactive oxygen species without disrupting normal antioxidant balance. (Journal of Clinical Otorhinolaryngology Head and Neck Surgery, 2013.)", "assessment": "This is a review / theoretical paper on oxidative stress in inner ear disease. The argument for H₂ selectivity is mechanistically sound and well-documented in the broader H₂ literature, but this paper presents no new experimental data — specifically no clinical or animal studies of H₂ for hearing loss or tinnitus. It should be read as a hypothesis-generating theoretical argument, not as clinical evidence. The selectivity of H₂ for ·OH and ONOO⁻ is a key mechanistic advantage that merits further experimental investigation in otology.", "abstract": "Free radicals are atoms, molecules or ions with unpaired electrons. In biological systems, free radicals can have a dual role, being beneficial in some situations and deleterious in others. Free radicals are required for normal cellular metabolism, but they lead to cellular degeneration if overproduced. To prevent the excessive buildup of free radicals, cells have developed an elaborate series of antioxidant enzymes that counteract oxidative stress and protect cells by maintaining the proper balance of oxidation and anti-oxidation. Therefore, when there is an oxidant/anti-oxidant imbalance, no matter what direction, cells are likely to be damaged. Numerous reports in the literature indicate that free radicals play important roles in diseases of the inner ear as a result of noise exposure, ototoxic drugs, aging, and other pathological conditions. Therefore, there have been many attempts to employ antioxidants treat inner ear damage. However, antioxidant therapy could be harmful if the improper compound or dose is employed. Effective antioxidant therapy requires prior knowledge of the type(s) of oxidative stress occurring in real time in the inner ear. Since most techniques for detecting free radicals in the inner ear are not clinically feasible, systemic anti-oxidant therapy is generally performed \"blindly\" and therefore likely to disrupt normal antioxidant levels in the inner ear or elsewhere in the body. If only a single anti-oxidant is used to treat a disease, it may disturb subsequent steps the oxidative/anti-oxidative chain reaction. An alternative approach, hydrogen therapy represents a promising therapeutic tool because it can selectively scavenge the strongest oxidant species, the hydroxyl radical and peroxynitrite anion, without disturbing normal oxidant/anti-oxidant cellular processes. In addition, hydrogen has no cytotoxic effects to cells so that it provides a near ideal therapy to eliminate toxic free radicals.", "conclusion": "An alternative approach, hydrogen therapy represents a promising therapeutic tool because it can selectively scavenge the strongest oxidant species, the hydroxyl radical and peroxynitrite anion, without disturbing normal oxidant/anti-oxidant cellular processes. In addition, hydrogen has no cytotoxic effects to cells so that it provides a near ideal therapy to eliminate toxic free radicals." }, { "pmid": "24155664", "year": 2013, "title": "Hydrogen as a new class of radioprotective agent.", "title_en": null, "title_de": "Wasserstoff als eine neue Klasse von Radioprotektoren", "journal": "International journal of biological sciences", "authors": "Qian et al.", "author_search": "qian qian", "doi": "10.7150/ijbs.7220", "doi_url": "https://doi.org/10.7150/ijbs.7220", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/24155664/", "url": "https://h2medicine.org/studies/study-qian-2013-class-radioprotective-agent/", "methods": [ "saline-iv", "drinking-hrw" ], "indications": [ "cancer", "skin-aging", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2013 · Qian — Hydrogen as a new class of radioprotective agent", "summary": "Molecular hydrogen (H₂) reduces radiation-induced oxidative damage by selectively neutralizing hydroxyl radicals — the main cause of ionizing radiation injury. This review summarizes the authors' own research and independent replications in animal models, plus one randomized placebo-controlled human study showing that hydrogen-rich water reduced oxidative stress markers in cancer patients undergoing radiotherapy without impairing the anti-tumor effect. (International Journal of Biological Sciences, 2013.)", "assessment": "This review provides a well-structured overview of H₂ as a radioprotective agent, anchored by animal and one human randomized controlled study. The mechanistic rationale (·OH selectivity) is strong. The human clinical evidence at the time of writing was limited to one small study. As a review, it cannot itself prove efficacy — but it accurately represents the state of evidence in 2013. The field has since produced additional studies. The practical conclusion — hydrogen-rich water for radiotherapy patients — is a genuinely interesting hypothesis with early supporting evidence. No overstatement: this is one small RCT and animal work, not a confirmed standard of care.", "abstract": "It is well known that most of the ionizing radiation-induced damage is caused by hydroxyl radicals (·OH) follows radiolysis of H2O. Molecular hydrogen (H2) has antioxidant activities by selectively reducing ·OH and peroxynitrite(ONOO-). We firstly hypothesized and demonstrated the radioprotective effect of H2 in vitro and in vivo, which was also repeated on different experimental animal models by different departments. A randomized, placebo-controlled study showed that consumption of hydrogen-rich water reduces the biological reaction to radiation-induced oxidative stress without compromising anti-tumor effects. These encouraging results suggested that H2 represents a potentially novel preventative strategy for radiation-induced oxidative injuries. H2 is explosive. Therefore, administration of hydrogen-rich solution (physiological saline/pure water/other solutions saturated with H2) may be more practical in daily life and more suitable for daily consumption. This review focuses on major scientific and clinical advances of hydrogen-rich solution/H2 as a new class of radioprotective agent.", "conclusion": "Therefore, administration of hydrogen-rich solution (physiological saline/pure water/other solutions saturated with H2) may be more practical in daily life and more suitable for daily consumption. This review focuses on major scientific and clinical advances of hydrogen-rich solution/H2 as a new class of radioprotective agent." }, { "pmid": "24132155", "year": 2013, "title": "Multiple hits, including oxidative stress, as pathogenesis and treatment target in non-alcoholic steatohepatitis (NASH).", "title_en": null, "title_de": "Multiple Schädigungen, einschließlich oxidativem Stress, als Pathogenese und Behandlungsziel bei der nichtalkoholischen Steatohepatitis (NASH)", "journal": "International journal of molecular sciences", "authors": "Takaki et al.", "author_search": "takaki takaki", "doi": "10.3390/ijms141020704", "doi_url": "https://doi.org/10.3390/ijms141020704", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/24132155/", "url": "https://h2medicine.org/studies/study-takaki-2013-multiple-hits-including-oxidative/", "methods": [ "drinking-hrw" ], "indications": [ "diabetes", "liver", "cardiovascular", "cancer", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2013 · Takaki — Multiple hits, including oxidative stress, as pathogenesis and treatment target in non-alcoholic steatohepatitis (NASH)", "summary": "Non-alcoholic steatohepatitis (NASH) progresses through multiple simultaneous pathways — including insulin resistance, gut microbiota, and oxidative stress — and conventional antioxidants have failed in long-term trials because they act non-selectively. This review argues that molecular hydrogen, which selectively reduces only cytotoxic reactive oxygen species, represents a more targeted approach, citing animal evidence that hydrogen-rich water can slow the progression from NASH to hepatocellular carcinoma. (International Journal of Molecular Sciences, 2013.)", "assessment": "This is a narrative review addressing NASH pathogenesis and the potential role of H₂. The mechanistic argument is coherent. The animal evidence for H₂ slowing NASH progression is cited but not detailed here. No human clinical data are presented for H₂ in NASH. The authors call for long-term clinical studies — an honest acknowledgment that human evidence was lacking in 2013. This review is useful as a mechanistic background paper, not as clinical proof of effect. NASH is a complex multifactorial disease; no single intervention, including H₂, has yet demonstrated conclusive long-term benefit in humans.", "abstract": "Multiple parallel hits, including genetic differences, insulin resistance and intestinal microbiota, account for the progression of non-alcoholic steatohepatitis (NASH). Multiple hits induce adipokine secretion, endoplasmic reticulum (ER) and oxidative stress at the cellular level that subsequently induce hepatic steatosis, inflammation and fibrosis, among which oxidative stress is considered a key contributor to progression from simple fatty liver to NASH. Although several clinical trials have shown that anti-oxidative therapy can effectively control hepatitis activities in the short term, the long-term effect remains obscure. Several trials of long-term anti-oxidant protocols aimed at treating cerebrovascular diseases or cancer development have failed to produce a benefit. This might be explained by the non-selective anti-oxidative properties of these drugs. Molecular hydrogen is an effective antioxidant that reduces only cytotoxic reactive oxygen species (ROS) and several diseases associated with oxidative stress are sensitive to hydrogen. The progress of NASH to hepatocellular carcinoma can be controlled using hydrogen-rich water. Thus, targeting mitochondrial oxidative stress might be a good candidate for NASH treatment. Long term clinical intervention is needed to control this complex lifestyle-related disease.", "conclusion": "Thus, targeting mitochondrial oxidative stress might be a good candidate for NASH treatment. Long term clinical intervention is needed to control this complex lifestyle-related disease." }, { "pmid": "23921897", "year": 2013, "title": "Why does brain metabolism not favor burning of fatty acids to provide energy? Reflections on disadvantages of the use of free fatty acids as fuel for brain.", "title_en": null, "title_de": "Warum bevorzugt der Gehirnstoffwechsel nicht die Verbrennung von Fettsäuren zur Energiegewinnung? Überlegungen zu den Nachteilen der Verwendung freier Fettsäuren als Brennstoff für das Gehirn", "journal": "Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism", "authors": "Schönfeld et al.", "author_search": "schönfeld schönfeld", "doi": "10.1038/jcbfm.2013.128", "doi_url": "https://doi.org/10.1038/jcbfm.2013.128", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/23921897/", "url": "https://h2medicine.org/studies/study-schoenfeld-2013-why-does-brain-metabolism/", "methods": [ "unspecified" ], "indications": [ "metabolic", "neurology", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2013 · Schönfeld — Why does brain metabolism not favor burning of fatty acids to provide energy? Reflections on disadvantages of the use of free fatty acids as fuel for brain", "summary": "The brain almost exclusively uses glucose rather than fatty acids as fuel — this review explains why: fatty acid oxidation in neurons generates more oxidative stress, demands more oxygen, and produces ATP more slowly than glucose oxidation. The connection to hydrogen in this paper is the biochemical role of superoxide (a reactive oxygen species) generated during mitochondrial fatty acid beta-oxidation — not therapeutic molecular hydrogen (H₂). (Journal of Cerebral Blood Flow and Metabolism, 2013.)", "assessment": "This is a neuroscience/biochemistry review with no relevance to therapeutic molecular hydrogen (H₂). The word „hydrogen“ appears only in its chemical context (fatty acid C–H bonds, superoxide chemistry). The paper provides no evidence — positive or negative — for H₂ as a health intervention. It is indexed in the H₂ database due to keyword overlap. The science is high quality and relevant to understanding brain metabolism and neurological disease, but has no application to H₂ medicine.", "abstract": "It is puzzling that hydrogen-rich fatty acids are used only poorly as fuel in the brain. The long-standing belief that a slow passage of fatty acids across the blood-brain barrier might be the reason. However, this has been corrected by experimental results. Otherwise, accumulated nonesterified fatty acids or their activated derivatives could exert detrimental activities on mitochondria, which might trigger the mitochondrial route of apoptosis. Here, we draw attention to three particular problems: (1) ATP generation linked to β-oxidation of fatty acids demands more oxygen than glucose, thereby enhancing the risk for neurons to become hypoxic; (2) β-oxidation of fatty acids generates superoxide, which, taken together with the poor anti-oxidative defense in neurons, causes severe oxidative stress; (3) the rate of ATP generation based on adipose tissue-derived fatty acids is slower than that using blood glucose as fuel. Thus, in periods of extended continuous and rapid neuronal firing, fatty acid oxidation cannot guarantee rapid ATP generation in neurons. We conjecture that the disadvantages connected with using fatty acids as fuel have created evolutionary pressure on lowering the expression of the β-oxidation enzyme equipment in brain mitochondria to avoid extensive fatty acid oxidation and to favor glucose oxidation in brain.", "conclusion": "Thus, in periods of extended continuous and rapid neuronal firing, fatty acid oxidation cannot guarantee rapid ATP generation in neurons. We conjecture that the disadvantages connected with using fatty acids as fuel have created evolutionary pressure on lowering the expression of the β-oxidation enzyme equipment in brain mitochondria to avoid extensive fatty acid oxidation and to favor glucose oxi" }, { "pmid": "23859555", "year": 2013, "title": "Molecular hydrogen: new antioxidant and anti-inflammatory therapy for rheumatoid arthritis and related diseases.", "title_en": null, "title_de": "Molekularer Wasserstoff: neue antioxidative und antiinflammatorische Therapie für rheumatoide Arthritis und verwandte Erkrankungen", "journal": "Current pharmaceutical design", "authors": "Ishibashi", "author_search": "ishibashi ishibashi", "doi": "10.2174/13816128113199990507", "doi_url": "https://doi.org/10.2174/13816128113199990507", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/23859555/", "url": "https://h2medicine.org/studies/study-ishibashi-2013-antioxidant-anti-inflammatory-rheumatoid/", "methods": [ "unspecified" ], "indications": [ "cardiovascular", "joints-rheumatology", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2013 · Ishibashi — Molecular hydrogen: new antioxidant and anti-inflammatory therapy for rheumatoid arthritis and related diseases", "summary": "Reactive oxygen species (ROS) — especially the hydroxyl radical — play a central role in the joint destruction and systemic inflammation of rheumatoid arthritis (RA), and molecular hydrogen (H₂) selectively neutralizes exactly this radical. This review argues that H₂ represents a promising complement to conventional RA therapy by reducing oxidative stress at early disease stages, potentially also preventing the associated cardiovascular risk. (Current Pharmaceutical Design, 2013.)", "assessment": "This is a review article on H₂ in rheumatoid arthritis with a sound mechanistic rationale. It references early clinical trial data supporting H₂ as an adjunct to RA therapy — this is stronger evidence than pure animal work, but the clinical trials cited were small. The potential to also reduce RA-associated cardiovascular risk via H₂ antioxidant effects is an interesting hypothesis not yet confirmed in long-term human studies. No overstatement: H₂ is not a replacement for established RA biologics, and long-term controlled trials in RA are still needed. The review accurately characterizes the state of evidence circa 2013.", "abstract": "Rheumatoid arthritis (RA) is a chronic inflammatory disease in which the progressive destruction of joint causes morbidity. It is also associated with an increased risk of atherosclerosis, which can result in cardiovascular disease and mortality. The therapeutic goal is to control the systemic inflammation to obtain not only the remission of symptoms, but also improve general state of health. Although recent biologic immunosuppressive therapies targeting pro-inflammatory cytokines have spawned a paradigm shift regarding the prognosis of RA, these therapies possess inherent side effects. Also, early diagnosis of the disease remains confounded by uncertainty. While the mechanisms responsible for the onset of RA remain unclear, reactive oxygen species (ROS) play a significant role in the pathogenesis of RA. ROS play a central role both upstream and downstream of NF-κB and TNFα pathways, which are located at the center of the inflammatory response. Among the ROS, the hydroxyl radical is the most harmful, and molecular hydrogen (H2) is a selective scavenger for this species. Recently, it has been shown that H2 is useful when administered along with the conventional therapy in RA as it acts to reduce oxidative stress in the patients. Especially in the early stage, H2 showed significant therapeutic potential, which also seemed to assist diagnosis and treatment decisions of RA. The possible expectations regarding the potential benefits of H2 by reducing the oxidative stress, resulting from inflammatory factors, are raised and discussed here. They include prevention of RA and related atherosclerosis, as well as therapeutic validity for RA.", "conclusion": "The possible expectations regarding the potential benefits of H2 by reducing the oxidative stress, resulting from inflammatory factors, are raised and discussed here. They include prevention of RA and related atherosclerosis, as well as therapeutic validity for RA." }, { "pmid": "23436141", "year": 2013, "title": "Role of the Toll Like receptor (TLR) radical cycle in chronic inflammation: possible treatments targeting the TLR4 pathway.", "title_en": null, "title_de": "Rolle des Toll-Like-Rezeptor-(TLR-)Radikalzyklus bei chronischer Entzündung: mögliche Behandlungen mit Zielrichtung auf den TLR4-Signalweg", "journal": "Molecular neurobiology", "authors": "Lucas et al.", "author_search": "lucas lucas", "doi": "10.1007/s12035-013-8425-7", "doi_url": "https://doi.org/10.1007/s12035-013-8425-7", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/23436141/", "url": "https://h2medicine.org/studies/study-lucas-2013-toll-like-receptor-tlr/", "methods": [ "inhalation" ], "indications": [ "diabetes", "metabolic", "sports-exercise", "neurology", "cardiovascular", "cancer", "respiratory", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2013 · Lucas — Role of the Toll Like receptor (TLR) radical cycle in chronic inflammation: possible treatments targeting the TLR4 pathway", "summary": "Activation of the Toll-like receptor 4 (TLR4) pathway — triggered by environmental factors such as ozone, particulate matter, ionizing radiation, and LPS from bacteria — may underlie a wide spectrum of chronic inflammatory and neuropsychiatric diseases. This review covers a large number of potential therapeutic agents that target TLR4 and the resulting ROS/RNS cycle, including molecular hydrogen as one of the most selective and safe candidates. (Molecular Neurobiology, 2013.)", "assessment": "This is a very broad narrative review linking TLR4 immunology to an extensive list of chronic diseases and surveying multiple potential therapeutic agents. Molecular hydrogen is listed as one candidate among many, not as the central subject. The review presents no original H₂ experimental data. Its breadth is also its limitation: the hypothesis that TLR4 radical cycling underlies all listed „civilization diseases“ is ambitious and remains partially speculative. H₂ is positioned plausibly as a ROS/RNS modulator, but no RA- or disease-specific H₂ clinical data are presented. Useful as a mechanistic map, not as clinical evidence for H₂.", "abstract": "Activation of the Toll-like receptor 4 (TLR4) complex, a receptor of the innate immune system, may underpin the pathophysiology of many human diseases, including asthma, cardiovascular disorder, diabetes, obesity, metabolic syndrome, autoimmune disorders, neuroinflammatory disorders, schizophrenia, bipolar disorder, autism, clinical depression, chronic fatigue syndrome, alcohol abuse, and toluene inhalation. TLRs are pattern recognition receptors that recognize damage-associated molecular patterns and pathogen-associated molecular patterns, including lipopolysaccharide (LPS) from gram-negative bacteria. Here we focus on the environmental factors, which are known to trigger TLR4, e.g., ozone, atmosphere particulate matter, long-lived reactive oxygen intermediate, pentachlorophenol, ionizing radiation, and toluene. Activation of the TLR4 pathways may cause chronic inflammation and increased production of reactive oxygen and nitrogen species (ROS/RNS) and oxidative and nitrosative stress and therefore TLR-related diseases. This implies that drugs or substances that modify these pathways may prevent or improve the abovementioned diseases. Here we review some of the most promising drugs and agents that have the potential to attenuate TLR-mediated inflammation, e.g., anti-LPS strategies that aim to neutralize LPS (synthetic anti-LPS peptides and recombinant factor C) and TLR4/MyD88 antagonists, including eritoran, CyP, EM-163, epigallocatechin-3-gallate, 6-shogaol, cinnamon extract, N-acetylcysteine, melatonin, and molecular hydrogen. The authors posit that activation of the TLR radical (ROS/RNS) cycle is a common pathway underpinning many \"civilization\" disorders and that targeting the TLR radical cycle may be an effective method to treat many inflammatory disorders.", "conclusion": "Here we review some of the most promising drugs and agents that have the potential to attenuate TLR-mediated inflammation, e.g., anti-LPS strategies that aim to neutralize LPS (synthetic anti-LPS peptides and recombinant factor C) and TLR4/MyD88 antagonists, including eritoran, CyP, EM-163, epigallocatechin-3-gallate, 6-shogaol, cinnamon extract, N-acetylcysteine, melatonin, and molecular hydrogen" }, { "pmid": "24127924", "year": 2013, "title": "Effect of hydrogen-rich water on oxidative stress, liver function, and viral load in patients with chronic hepatitis B.", "title_en": null, "title_de": "Wirkung von wasserstoffreichem Wasser auf oxidativen Stress, Leberfunktion und Viruslast bei Patienten mit chronischer Hepatitis B.", "journal": "Clinical and translational science", "authors": "Xia et al.", "author_search": "xia xia", "doi": "10.1111/cts.12076", "doi_url": "https://doi.org/10.1111/cts.12076", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/24127924/", "url": "https://h2medicine.org/studies/study-xia-2013-oxidative-stress-liver-function/", "methods": [ "drinking-hrw" ], "indications": [ "liver", "oxidative-stress" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2013 · Xia et al. — Effect of hydrogen-rich water on oxidative stress, liver function, and viral load in patients with chronic hepatitis B.", "summary": "In 60 patients with chronic hepatitis B, adding hydrogen-rich water (1,200–1,800 mL/day for 6 weeks) to routine antiviral treatment markedly reduced oxidative stress markers — while liver function and HBV DNA levels improved similarly in both groups. HRW showed a specific anti-oxidative effect without a detectable antiviral advantage in this short trial. (Clinical and Translational Science, 2013.)", "assessment": "An honest and informative study. The positive finding — HRW reduces oxidative stress in hepatitis B patients — is clear and statistically significant. The null finding — no additional benefit over standard treatment for liver enzymes or HBV viral load — must be reported with equal prominence. Whether oxidative stress reduction in 6 weeks would translate into clinically meaningful outcomes (fibrosis reduction, virological control) over years remains unknown. Limitations: short duration (6 weeks), relatively small n (30 per group), no long-term follow-up, the antiviral mechanism of action is biologically implausible (H₂ is not an antiviral agent).", "abstract": "OBJECTIVE: To investigate effects of hydrogen-rich water (HRW) on oxidative stress, liver function and HBV DNA in patients with chronic hepatitis B (CHB). METHODS: Sixty patients with CHB were randomly assigned into routine treatment group or hydrogen treatment group in which patients received routine treatment alone or additional oral HRW (1200-1800 mL/day, twice daily), respectively, for 6 consecutive weeks. Serum oxidative stress, liver function, and HBV DNA level were detected before and after treatment. Thirty healthy subjects served as controls. RESULTS: When compared with controls, oxidative stress was obvious in CHB patients, and the liver function also significantly impaired. After treatment, the oxidative stress remained unchanged in routine treatment group, but markedly improved in hydrogen treatment group. The liver function was improved significantly and the HBV DNA reduced markedly after corresponding treatments. Although a significant difference was noted in the oxidative stress between two groups after treatment, the liver function and HBV DNA level were comparable after treatment and both had improved tendencies. CONCLUSION: HRW significantly attenuates oxidative stress in CHB patients, but further study with long-term treatment is required to confirm the effect of HRW on liver function and HBV DNA level.", "conclusion": "HRW significantly attenuates oxidative stress in CHB patients, but further study with long-term treatment is required to confirm the effect of HRW on liver function and HBV DNA level." }, { "pmid": "23400965", "year": 2013, "title": "Pilot study of H₂ therapy in Parkinson's disease: a randomized double-blind placebo-controlled trial.", "title_en": null, "title_de": "Pilotstudie zur H₂-Therapie bei der Parkinson-Krankheit: eine randomisierte, doppelblinde, placebokontrollierte Studie.", "journal": "Movement disorders : official journal of the Movement Disorder Society", "authors": "Yoritaka et al.", "author_search": "yoritaka yoritaka", "doi": "10.1002/mds.25375", "doi_url": "https://doi.org/10.1002/mds.25375", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/23400965/", "url": "https://h2medicine.org/studies/study-yoritaka-2013-parkinson-disease/", "methods": [ "drinking-hrw" ], "indications": [ "neurology", "oxidative-stress" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2013 · Yoritaka et al. — Pilot study of H₂ therapy in Parkinson's disease: a randomized double-blind placebo-controlled trial.", "summary": "In a 48-week double-blind, placebo-controlled pilot trial, 17 levodopa-medicated Parkinson's patients drinking 1,000 mL/day of H₂-rich water showed improved UPDRS motor scores on average, while the placebo group worsened — a statistically significant difference despite the small sample size. This is among the first rigorous RCTs of H₂ in a neurodegenerative disease. (Movement Disorders, 2013.)", "assessment": "A landmark pilot study for H₂ in neurology. The positive result in an objective, validated scale (UPDRS) is statistically significant and clinically plausible given H₂'s antioxidant mechanism. However, the study is severely limited by n=9 vs. n=8 — far too small for definitive conclusions. Large standard deviations indicate high individual variability. The study was not powered for definitive efficacy, and results should not be extrapolated beyond their role as a hypothesis-generating pilot. A larger, multi-center RCT in PD is needed (and has been conducted in subsequent years). No safety concerns identified.", "abstract": "BACKGROUND: Oxidative stress is involved in the progression of Parkinson's disease (PD). Recent studies have confirmed that molecular hydrogen (H₂) functions as a highly effective antioxidant in cultured cells and animal models. Drinking H₂-dissolved water (H₂-water) reduced oxidative stress and improved Parkinson's features in model animals. METHODS: In this a placebo-controlled, randomized, double-blind, parallel-group clinical pilot study, the authors assessed the efficacy of H₂ -water in Japanese patients with levodopa-medicated PD. Participants drank 1,000 mL/day of H₂-water or pseudo water for 48 weeks. RESULTS: Total Unified Parkinson's Disease Rating Scale (UPDRS) scores in the H₂-water group (n=9) improved (median, -1.0; mean ± standard deviation, -5.7 ± 8.4), whereas UPDRS scores in the placebo group (n=8) worsened (median, 4.5; mean ± standard deviation, 4.1 ± 9.2). Despite the minimal number of patients and the short duration of the trial, the difference was significant (P<0.05). CONCLUSIONS: The results indicated that drinking H₂-water was safe and well tolerated, and a significant improvement in total UPDRS scores for patients in the H₂-water group was demonstrated.", "conclusion": "The results indicated that drinking H₂-water was safe and well tolerated, and a significant improvement in total UPDRS scores for patients in the H₂-water group was demonstrated." }, { "pmid": "23374763", "year": 2013, "title": "Effect of supplementation with hydrogen-rich water in patients with interstitial cystitis/painful bladder syndrome.", "title_en": null, "title_de": "Wirkung der Supplementierung mit wasserstoffreichem Wasser bei Patienten mit interstitieller Zystitis/Blasenschmerzsyndrom.", "journal": "Urology", "authors": "Matsumoto et al.", "author_search": "matsumoto matsumoto", "doi": "10.1016/j.urology.2012.10.026", "doi_url": "https://doi.org/10.1016/j.urology.2012.10.026", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/23374763/", "url": "https://h2medicine.org/studies/study-matsumoto-2013-supplementation-interstitial-cystitis-painful/", "methods": [ "drinking-hrw" ], "indications": [ "other" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2013 · Matsumoto et al. — Effect of supplementation with hydrogen-rich water in patients with interstitial cystitis/painful bladder syndrome.", "summary": "In a double-blind, placebo-controlled RCT in 30 patients with interstitial cystitis/painful bladder syndrome (IC/PBS), hydrogen-rich water did not significantly outperform placebo on any primary symptom endpoint after 8 weeks — though an exceptional responder rate (11%) was noted. The authors do not recommend HRW for IC/PBS based on these results. (Urology, 2013.)", "assessment": "A well-designed trial with a clearly negative primary result: HRW showed no statistically significant benefit over placebo for IC/PBS symptoms. Both groups improved equally, consistent with a strong placebo effect or natural disease fluctuation. The possible 11% exceptional-responder signal is interesting but not actionable at this sample size. Limitations: small n (28 evaluable), 8-week duration may be short for a chronic condition, single-center, predominantly female population. This honest null result is an important contribution to the evidence base — it rules out a broad, non-specific anti-inflammatory effect of HRW in IC/PBS at standard dosing.", "abstract": "OBJECTIVE: To investigate the efficacy of hydrogen-rich water for the treatment of patients with interstitial cystitis/painful bladder syndrome (IC/PBS). METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled clinical trial of hydrogen-rich water in patients with IC/PBS. Inclusion criteria were stable symptoms of IC/PBS for ≥ 12 weeks after bladder hydrodistension, Interstitial Cystitis Symptom Index score of ≥ 7 and bladder pain (question 4 on Interstitial Cystitis Symptom Index) of ≥ 4. They were randomized by a 2:1 ratio to receive hydrogen-rich water or placebo water for 8 weeks. The symptoms were assessed using the Interstitial Cystitis Symptom Index, Interstitial Cystitis Problem Index, Parsons' Pelvic Pain and Urgency/Frequency Patient Symptom Scale, visual analog scale bladder pain scores, and a standard 3-day voiding diary. The primary outcome was improvement of patient-reported symptoms evaluated after treatment. RESULTS: A total of 30 participants (29 women and 1 man, age 64.0 ± 14.8 years) were enrolled in the present study, and 2 patients (both women) were withdrawn from the study. The score of bladder pain was significantly reduced in both groups. However, the effect of hydrogen-rich water on symptoms was not significantly different from that of placebo, although supplementation with hydrogen-rich water was extremely effective in improving the bladder pain score in 11% of the patients. CONCLUSION: The results of the present study do not support the use of supplementation with hydrogen-rich water for treating patients with IC/PBS.", "conclusion": "The results of the present study do not support the use of supplementation with hydrogen-rich water for treating patients with IC/PBS." }, { "pmid": "24423914", "year": 2013, "title": "[Regulative effects of hydrogen-rich medium on monocytic adhesion and vascular endothelial permeability].", "title_en": null, "title_de": "Regulierende Wirkungen von wasserstoffreichem Medium auf die monozytäre Adhäsion und die vaskuläre Endothelpermeabilität", "journal": "Zhonghua yi xue za zhi", "authors": "Wang et al.", "author_search": "wang wang", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/24423914/", "url": "https://h2medicine.org/studies/study-wang-2013-regulative-medium-monocytic-adhesion/", "methods": [ "unspecified" ], "indications": [ "cardiovascular" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2013 · Wang — Regulative effects of hydrogen-rich medium on monocytic adhesion and vascular endothelial permeability", "summary": "In this in-vitro study, hydrogen-rich culture medium significantly reduced the LPS-induced adhesion of monocytes to endothelial cells, lowered inflammatory adhesion molecules (E-selectin, VCAM-1), and protected vascular endothelial integrity (VE-cadherin). These findings suggest that H₂ may help counteract early-stage vascular inflammation triggered by bacterial endotoxin — though this is a cell culture study, not human evidence. (Zhonghua Yi Xue Za Zhi, 2013.)", "assessment": "This is a preclinical in-vitro study demonstrating H₂ protective effects on vascular endothelial cells under inflammatory challenge. The findings are biologically plausible and the experimental design is solid for a cell study. Results cannot be directly extrapolated to humans: HUVEC culture models remove the complex interactions of the immune system, blood flow, and systemic physiology. No clinical conclusions about vascular protection in humans can be drawn. The study contributes to mechanistic understanding of how H₂ may protect against endotoxin-induced vascular inflammation — a pathway relevant to sepsis and atherosclerosis research.", "abstract": "OBJECTIVE: To explore the regulative effects of hydrogen-rich medium on lipopolysaccharide (LPS)-induced monocytes adhesion to human umbilical vein endothelial cells (HUVEC) and vascular endothelial permeability in vitro. METHODS: Endothelial cells were seeded in 6-well plates and randomly divided into 4 groups (n = 42 each):control (A), hydrogen-rich medium (B), LPS (C) and LPS+hydrogen-rich medium (D). Cells were cultured in plain culture medium in groups A and C or in hydrogen-saturated culture medium in groups B and D.LPS 1 µg/ml was added into groups C and D.When forming a monolayer, monocytes were added into each group after 6, 12 and 24 h respectively. After a 90-minute co-culturing, adhesion status was detected by Wright-Giemsa stain.Supernatants were collected to detect the concentrations of vascular cell adhesion molecule-1 (VCAM-1) and E-selectin by enzyme-linked immunosorbent assay (ELISA). The expression of VE-cadherin was measured by Western blot. Cells were stained with immunofluorescence to show the distribution of VE-cadherin after a 24-hour incubation. RESULTS: Compared with group A, the adhesion of monocytes to endothelial cells increased (P < 0.05) in group C, the levels of E-selectin and VCAM-1 became elevated (P < 0.05) while the expression of VE-cadherin decreased significantly (P < 0.05). Compared with group C, adhesion decreased in group D (P < 0.05), the levels of E-selectin and VCAM-1 decreased (P < 0.05) while there was an increased expression of VE-cadherin (P < 0.05). Three timepoints showed the same tendency. The results of 24 h fluorescence indicated that, compared with group A, VE-cadherin was incomplete in cell-cell connections in group C.However it was complete and well-distributed in group D versus group C. CONCLUSION: Hydrogen-rich medium may reduce the LPS-induced release of adhesion molecules, lessen monocytic adhesion to HUVEC and regulate the expression of VE-cadherin to protect vascular permeability.", "conclusion": "Hydrogen-rich medium may reduce the LPS-induced release of adhesion molecules, lessen monocytic adhesion to HUVEC and regulate the expression of VE-cadherin to protect vascular permeability." }, { "pmid": "24001618", "year": 2013, "title": "A non-aqueous reduction process for purifying ¹⁵³Gd produced in natural europium targets.", "title_en": null, "title_de": "Ein nichtwässriges Reduktionsverfahren zur Aufreinigung von ¹⁵³Gd, das in natürlichen Europium-Targets erzeugt wird", "journal": "Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine", "authors": "Johnsen et al.", "author_search": "johnsen johnsen", "doi": "10.1016/j.apradiso.2013.07.025", "doi_url": "https://doi.org/10.1016/j.apradiso.2013.07.025", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/24001618/", "url": "https://h2medicine.org/studies/study-johnsen-2013-non-aqueous-reduction-process/", "methods": [ "inhalation" ], "indications": [ "skin-aging" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2013 · Johnsen — A non-aqueous reduction process for purifying ¹⁵³Gd produced in natural europium targets", "summary": "This nuclear medicine radiochemistry study developed a methanol-based purification process for Gadolinium-153 (a medical imaging quality-assurance isotope) that nearly eliminates the hazardous hydrogen gas produced by conventional aqueous europium reduction. The hydrogen in this paper is a flammability hazard in radiological hot cells — not therapeutic molecular hydrogen (H₂). (Applied Radiation and Isotopes, 2013.)", "assessment": "This is a technical radiochemistry paper with no relevance to therapeutic or biological molecular hydrogen. H₂ gas here is an industrial process byproduct that poses a safety hazard and must be eliminated. This entry is in the H₂ database solely due to keyword matching. No conclusions whatsoever about H₂ health effects can be derived from this paper.", "abstract": "Gadolinium-153 is a low-energy gamma-emitter used in nuclear medicine imaging quality assurance. Produced in nuclear reactors using natural Eu₂O₃ targets, ¹⁵³Gd is radiochemically separated from europium isotopes by europium reduction. However, conventional aqueous europium reduction produces hydrogen gas, a flammability hazard in radiological hot cells. We altered the traditional reduction method, using methanol as the process solvent to nearly eliminate hydrogen gas production. This new, non-aqueous reduction process demonstrates greater than 98% europium removal and gadolinium yields of 90%.", "conclusion": "We altered the traditional reduction method, using methanol as the process solvent to nearly eliminate hydrogen gas production. This new, non-aqueous reduction process demonstrates greater than 98% europium removal and gadolinium yields of 90%." }, { "pmid": "23967088", "year": 2013, "title": "An in silico analysis of troponin I mutations in hypertrophic cardiomyopathy of Indian origin.", "title_en": null, "title_de": "Eine In-silico-Analyse von Troponin-I-Mutationen bei hypertropher Kardiomyopathie indischer Herkunft", "journal": "PloS one", "authors": "Ramachandran et al.", "author_search": "ramachandran ramachandran", "doi": "10.1371/journal.pone.0070704", "doi_url": "https://doi.org/10.1371/journal.pone.0070704", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/23967088/", "url": "https://h2medicine.org/studies/study-ramachandran-2013-silico-analysis-troponin-mutations/", "methods": [ "unspecified" ], "indications": [ "cardiovascular" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2013 · Ramachandran — An in silico analysis of troponin I mutations in hypertrophic cardiomyopathy of Indian origin", "summary": "Four mutations in the Troponin I gene (including one novel mutation) were identified in Indian patients with hypertrophic cardiomyopathy (HCM), and in-silico structural modeling showed these mutations disrupt intermolecular hydrogen bonds within the troponin complex, reducing protein stability and subunit interactions. This is a computational genetics study; the hydrogen bonds mentioned are molecular structural chemistry, not therapeutic H₂. (PLoS ONE, 2013.)", "assessment": "This is a computational/in-silico genetics study on hypertrophic cardiomyopathy mutations with no relevance to therapeutic molecular hydrogen (H₂). The hydrogen bonds described are protein biochemistry. The paper contributes to understanding genetic HCM in South Asian populations, which is valuable for cardiology. No conclusions about H₂ therapy can be drawn. This entry is indexed in the H₂ database due to keyword overlap only.", "abstract": "Hypertrophic Cardiomyopathy (HCM) is an autosomal dominant disorder of the myocardium which is hypertrophied resulting in arrhythmias and heart failure leading to sudden cardiac death (SCD). Several sarcomeric proteins and modifier genes have been implicated in this disease. Troponin I, being a part of the Troponin complex (troponin I, troponin C, troponin T), is an important gene for sarcomeric function. Four mutations (1 novel) were identified in Indian HCM cases, namely, Pro82Ser, Arg98Gln, Arg141Gln and Arg162Gln in Troponin I protein, which are in functionally significant domains. In order to analyse the effect of the mutations on protein stability and protein-protein interactions within the Troponin complex, an in silico study was carried out. The freely available X-ray crystal structure (PDB ID: 1JIE) was used as the template to model the protein followed by loop generation and development of troponin complex for both the troponin I wild type and four mutants (NCBI ID: PRJNA194382). The structural study was carried out to determine the effect of mutation on the structural stability and protein-protein interactions between three subunits in the complex. These mutations, especially the arginine to glutamine substitutions were found to result in local perturbations within the troponin complex by creating/removing inter/intra molecular hydrogen bonds with troponin T and troponin C. This has led to a decrease in the protein stability and loss of important interactions between the three subunits. It could have a significant impact on the disease progression when coupled with allelic heterogeneity which was observed in the cases carrying these mutations. However, this can be further confirmed by functional studies on protein levels in the identified cases.", "conclusion": "It could have a significant impact on the disease progression when coupled with allelic heterogeneity which was observed in the cases carrying these mutations. However, this can be further confirmed by functional studies on protein levels in the identified cases." }, { "pmid": "23871246", "year": 2013, "title": "Hydrogen-rich saline ameliorates renal injury induced by unilateral ureteral obstruction in rats.", "title_en": null, "title_de": "Wasserstoffreiche Kochsalzlösung lindert die durch einseitige Ureterobstruktion induzierte Nierenschädigung bei Ratten.", "journal": "International immunopharmacology", "authors": "Xu et al.", "author_search": "xu xu", "doi": "10.1016/j.intimp.2013.06.033", "doi_url": "https://doi.org/10.1016/j.intimp.2013.06.033", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/23871246/", "url": "https://h2medicine.org/studies/study-xu-2013-saline-ameliorates-renal-injury/", "methods": [ "saline-iv" ], "indications": [ "kidney-dialysis", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2013 · Xu et al. — Hydrogen-rich saline ameliorates renal injury induced by unilateral ureteral obstruction in rats.", "summary": "In a rat model of obstructive kidney disease, hydrogen-rich saline (H₂ dissolved in salt solution) significantly reduced kidney tissue damage, cell death, fibrosis, and oxidative stress markers compared with untreated obstructed animals. The study suggests that H₂ saline could be a novel strategy to protect against obstruction-induced renal injury — but these findings come entirely from an animal experiment and cannot be directly transferred to humans.", "assessment": "This is a preclinical animal study — no human data. The results are internally consistent and methodologically standard for this field, but the study is small, short-term, and uses only one dose of H₂ saline. Honest limitation: rat UUO models have a poor track record of translating to human renal disease therapies. The findings are hypothesis-generating, not practice-changing. Whether these effects would hold in humans with chronic kidney disease or post-obstructive nephropathy remains entirely untested.", "abstract": "Hydrogen has been demonstrated to have effective protection against tissue injuries caused by oxidative stress, inflammation, and apoptosis. This study investigated the efficacy of hydrogen-rich saline (HS) on the prevention of renal injury induced by unilateral ureteric obstruction (UUO) in rats. Male Sprague-Dawley rats were divided randomly into 4 groups: sham group, UUO group, UUO+saline group, and UUO+HS group. UUO was induced by ligation of the left ureter. 5ml/kg HRSS or saline was administered beginning 1day after UUO and for 10days thereafter. Rats were killed at 10days after UUO. Left kidneys were excised immediately for the tissue histologic examinations and biochemical assays. Renal injury scores in the UUO group and the UUO+saline group were significantly higher compared with those in the sham group. However, administration of HS significantly reduced the injury score. Apoptosis index was significantly increased in UUO group and the UUO+saline group. HS treatment also reduced the apoptosis index. Interstitial fibrosis and macrophage infiltration were obvious in UUO kidneys. However, HS treatment significantly reduced the fibrosis and infiltration of macrophage in UUO kidneys. Significant increase in the MDA level and decrease in the SOD activity were observed in UUO group and the UUO+saline group. MDA level of UUO+HS group was significantly reduced. In addition, SOD activity of was significantly improved after treatment of HS. The data provide a biochemical and histologic basis for HS acting as a novel therapeutic strategy for preventing the renal injury induced by UUO.", "conclusion": "In addition, SOD activity of was significantly improved after treatment of HS. The data provide a biochemical and histologic basis for HS acting as a novel therapeutic strategy for preventing the renal injury induced by UUO." }, { "pmid": "23852510", "year": 2013, "title": "Molecular hydrogen consumption in the human body during the inhalation of hydrogen gas.", "title_en": null, "title_de": "Verbrauch von molekularem Wasserstoff im menschlichen Körper während der Inhalation von Wasserstoffgas.", "journal": "Advances in experimental medicine and biology", "authors": "Shimouchi et al.", "author_search": "shimouchi shimouchi", "doi": "10.1007/978-1-4614-7411-1_42", "doi_url": "https://doi.org/10.1007/978-1-4614-7411-1_42", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/23852510/", "url": "https://h2medicine.org/studies/study-shimouchi-2013-consumption-body-during-inhalation/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2013 · Shimouchi et al. — Molecular hydrogen consumption in the human body during the inhalation of hydrogen gas.", "summary": "Using a gas chromatography method, this study measured the rate at which the human body consumes inhaled H₂ gas and confirmed a consumption rate of approximately 0.7 µmol/min/m² body surface area — closely matching prior data from H₂-rich water ingestion. The method is proposed as a noninvasive tool for monitoring hydroxyl radical production in the body. (Advances in Experimental Medicine and Biology, 2013.)", "assessment": "A physiological/mechanistic study rather than a clinical efficacy trial. Its contribution is methodological: establishing consistent H₂ consumption kinetics across delivery routes and identifying colonic fermentation as a key confound in breath H₂ measurements. The proposed use of exhaled H₂ as a noninvasive oxidative stress monitor is an intriguing concept but remains to be validated clinically. Limitations: sample size not reported in abstract (very small implied), no clinical endpoints, physiological measurements only. Evidence level is low by design — the study answers a mechanistic question, not a therapeutic one.", "abstract": "Inhaling or ingesting hydrogen (H2) gas improves oxidative stress-induced damage in animal models and humans. We previously reported that H2 was consumed throughout the human body after the ingestion of H2-rich water and that the H2 consumption rate ([Formula: see text]) was 1.0 μmol/min/m(2) body surface area. To confirm this result, we evaluated [Formula: see text]during the inhalation of low levels of H2 gas. After measuring the baseline levels of exhaled H2 during room air breathing via a one-way valve and a mouthpiece, the subject breathed low levels (160 ppm) of H2 gas mixed with purified artificial air. The H2 levels of their inspired and expired breath were measured by gas chromatography using a semiconductor sensor. [Formula: see text] was calculated using a ventilation equation derived from the inspired and expired concentrations of O2/CO2/H2, and the expired minute ventilation volume, which was measured with a respiromonitor. As a result, [Formula: see text] was found to be approximately 0.7 μmol/min/m(2)BSA, which was compatible with the findings we obtained using H2-rich water. [Formula: see text] varied markedly when pretreatment fasting to reduce colonic fermentation was not employed, i.e., when the subject's baseline breath hydrogen level was 10 ppm or greater. Our H2 inhalation method might be useful for the noninvasive monitoring of hydroxyl radical production in the human body.", "conclusion": "[Formula: see text] varied markedly when pretreatment fasting to reduce colonic fermentation was not employed, i.e., when the subject's baseline breath hydrogen level was 10 ppm or greater. Our H2 inhalation method might be useful for the noninvasive monitoring of hydroxyl radical production in the human body." }, { "pmid": "23786587", "year": 2013, "title": "Molecular hydrogen protects human lymphocyte AHH-1 cells against 12C6+ heavy ion radiation.", "title_en": null, "title_de": "Molekularer Wasserstoff schützt menschliche AHH-1-Lymphozytenzellen vor ¹²C⁶⁺-Schwerionenstrahlung.", "journal": "International journal of radiation biology", "authors": "Yang et al.", "author_search": "yang yang", "doi": "10.3109/09553002.2013.817704", "doi_url": "https://doi.org/10.3109/09553002.2013.817704", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/23786587/", "url": "https://h2medicine.org/studies/study-yang-2013-protects-lymphocyte-ahh-cells/", "methods": [ "unspecified" ], "indications": [ "cancer", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2013 · Yang et al. — Molecular hydrogen protects human lymphocyte AHH-1 cells against 12C6+ heavy ion radiation.", "summary": "In a cell culture experiment, molecular hydrogen (H₂) reduced reactive oxygen species (ROS), attenuated apoptosis, and alleviated cell cycle arrest in human lymphocyte cells exposed to heavy-ion radiation — a type of ionising radiation used in cancer radiotherapy and relevant to space travel. This is an in-vitro study; the results cannot be directly transferred to humans or clinical radiation settings.", "assessment": "An in-vitro cell study — no animal data, no human data. The experimental design is technically solid for the cell biology level, and the protective effects of H₂ against radiation-induced ROS are plausible. However, results from a single human cell line under saturated H₂ conditions provide very limited evidence for any clinical application. Honest limitation: radioprotection in a living organism is vastly more complex; cell line studies do not capture tissue pharmacokinetics, systemic immune responses, or DNA repair in the context of normal tissue heterogeneity. The conclusion that H₂ is a „safe and effective radioprotectant“ is premature at this stage — it is an interesting mechanistic observation worthy of further animal and eventually human study.", "abstract": "PURPOSE: To investigate the potential protective role of molecular hydrogen (H(2)) against (12)C(6+) heavy ion radiation, which is a major hazard for space travel and has been also widely used in heavy ion radiotherapy. MATERIALS AND METHODS: H(2) was dissolved in Roswell Park Memorial Institute (RPMI) 1640 medium under high pressure (0.4 Mpa) to a saturated level by using an apparatus produced by our department. A 2-[6-(4'-hydroxy) phenoxy-3H-xanthen-3-on-9-yl] benzoate (HPF) probe and a 2',7'-Dichlorodihydrofluorescein diacetate (H2DCFH-DA) fluorescent dye were used to measure the intracellular reactive oxygen species (ROS) level. Cell apoptosis were determined by double-staining with Annexin V-fluorescein isothiocyanate (Annexin V-FITC) and propidium iodide (PI) as well as a Hoechst 33342 staining method alternatively. Subsequently, cell cycle analysis was performed using a PI staining method and the expression of apoptotic protein was examined by Western blot. RESULTS: In this study, we demonstrated H(2) reduced ROS level in Human lymphocyte AHH-1 cells as well as in the radiolysis of water. Our data also showed H(2) attenuated (12)C(6+) radiation- induced cell apoptosis and also alleviated radiation-induced G2/M cell cycle arrest. Heavy ion radiation-induced Caspase 3 activation was also inhibited by H(2) treatment. CONCLUSION: In conclusion, these data showed that H(2) attenuated (12)C(6+) radiation-induced cell apoptosis through reducing the ROS level and modulating apoptotic molecules, thus indicating the potential of H(2) as a safe and effective radioprotectant.", "conclusion": "In conclusion, these data showed that H(2) attenuated (12)C(6+) radiation-induced cell apoptosis through reducing the ROS level and modulating apoptotic molecules, thus indicating the potential of H(2) as a safe and effective radioprotectant." }, { "pmid": "23610159", "year": 2013, "title": "Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome.", "title_en": null, "title_de": "Wasserstoffreiches Wasser senkt die Serum-LDL-Cholesterinspiegel und verbessert die HDL-Funktion bei Patienten mit potenziellem metabolischem Syndrom.", "journal": "Journal of lipid research", "authors": "Song et al.", "author_search": "song song", "doi": "10.1194/jlr.m036640", "doi_url": "https://doi.org/10.1194/jlr.m036640", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/23610159/", "url": "https://h2medicine.org/studies/study-song-2013-decreases-serum-ldl-cholesterol/", "methods": [ "drinking-hrw" ], "indications": [ "metabolic", "cardiovascular", "cancer", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2013 · Song et al. — Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome.", "summary": "In 20 patients with potential metabolic syndrome, drinking 0.9–1.0 L/day of H₂-rich water for 10 weeks reduced total cholesterol, LDL-cholesterol, and apolipoprotein B100/E, while significantly improving four distinct functional properties of HDL — including anti-oxidative protection of LDL and inhibition of inflammatory monocyte adhesion. Antioxidant enzyme SOD increased and lipid peroxidation markers fell. (Journal of Lipid Research, 2013.)", "assessment": "Scientifically rich findings with a significant methodological flaw: no placebo control group. Without a parallel control arm, the LDL and HDL changes could reflect spontaneous variation, dietary changes, or regression to the mean over 10 weeks. The four-functional-assay approach to HDL is a genuine strength and rarely seen in H₂ trials. The oxidative stress reductions (SOD increase, TBARS decrease) are internally consistent with the proposed H₂ mechanism. Limitations: no randomization, no control arm, small n (20), metabolic syndrome as an indication is multifactorial (diet, lifestyle confounders uncontrolled). Results are hypothesis-generating, not confirmatory.", "abstract": "We have found that hydrogen (dihydrogen; H2) has beneficial lipid-lowering effects in high-fat diet-fed Syrian golden hamsters. The objective of this study was to characterize the effects of H2-rich water (0.9-1.0 l/day) on the content, composition, and biological activities of serum lipoproteins on 20 patients with potential metabolic syndrome. Serum analysis showed that consumption of H2-rich water for 10 weeks resulted in decreased serum total-cholesterol (TC) and LDL-cholesterol (LDL-C) levels. Western blot analysis revealed a marked decrease of apolipoprotein (apo)B100 and apoE in serum. In addition, we found H2 significantly improved HDL functionality assessed in four independent ways, namely, i) protection against LDL oxidation, ii) inhibition of tumor necrosis factor (TNF)-α-induced monocyte adhesion to endothelial cells, iii) stimulation of cholesterol efflux from macrophage foam cells, and iv) protection of endothelial cells from TNF-α-induced apoptosis. Further, we found consumption of H2-rich water resulted in an increase in antioxidant enzyme superoxide dismutase and a decrease in thiobarbituric acid-reactive substances in whole serum and LDL. In conclusion, supplementation with H2-rich water seems to decrease serum LDL-C and apoB levels, improve dyslipidemia-injured HDL functions, and reduce oxidative stress, and it may have a beneficial role in prevention of potential metabolic syndrome.", "conclusion": "Further, we found consumption of H2-rich water resulted in an increase in antioxidant enzyme superoxide dismutase and a decrease in thiobarbituric acid-reactive substances in whole serum and LDL. In conclusion, supplementation with H2-rich water seems to decrease serum LDL-C and apoB levels, improve dyslipidemia-injured HDL functions, and reduce oxidative stress, and it may have a beneficial role " }, { "pmid": "23467041", "year": 2013, "title": "A surface-eroding poly(1,3-trimethylene carbonate) coating for fully biodegradable magnesium-based stent applications: toward better biofunction, biodegradation and biocompatibility.", "title_en": null, "title_de": "Oberflächenerodierende PTMC-Beschichtung für vollständig biologisch abbaubare magnesiumbasierte Stent-Anwendungen.", "journal": "Acta biomaterialia", "authors": "Wang et al.", "author_search": "wang wang", "doi": "10.1016/j.actbio.2013.02.041", "doi_url": "https://doi.org/10.1016/j.actbio.2013.02.041", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/23467041/", "url": "https://h2medicine.org/studies/study-wang-2013-surface-eroding-poly-trimethylene/", "methods": [ "inhalation" ], "indications": [ "sports-exercise", "cardiovascular", "immune-system" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2013 · Wang et al. — A surface-eroding poly(1,3-trimethylene carbonate) coating for fully biodegradable magnesium-based stent applications.", "summary": "This materials science study investigated a biodegradable polymer coating (PTMC) for magnesium-based cardiovascular stents — aiming to control corrosion and improve biocompatibility. Molecular hydrogen appears in this study only as a by-product of magnesium corrosion, not as a therapeutic agent. The study is not a hydrogen therapy trial; it is an in-vitro and in-vivo materials engineering study.", "assessment": "This is a materials science / biomedical engineering study — not a hydrogen therapy study. Molecular hydrogen is mentioned only as a corrosion by-product of biodegradable magnesium, and its absence (no accumulation) is framed as a positive safety outcome. Honest note: this paper is likely catalogued here due to H₂ keyword indexing; its relevance to therapeutic H₂ research is indirect at most. The materials findings are technically credible for stent development, but readers seeking H₂ therapy evidence should look elsewhere.", "abstract": "Biodegradable magnesium-based materials have a high potential for cardiovascular stent applications; however, there exist concerns on corrosion control and biocompatibility. A surface-eroding coating of poly(1,3-trimethylene carbonate) (PTMC) on magnesium (Mg) alloy was studied, and its dynamic degradation behavior, electrochemical corrosion, hemocompatibility and histocompatibility were investigated. The PTMC coating effectively protected the corrosion of the Mg alloy in the dynamic degradation test. The corrosion current density of the PTMC-coated alloy reduced by three orders and one order of magnitude compared to bare and poly(ε-caprolactone) (PCL)-coated Mg alloy, respectively. Static and dynamic blood tests in vitro indicated that significantly fewer platelets were adherent and activated, and fewer erythrocytes attached on the PTMC-coated surface and showed less hemolysis than on the controls. The PTMC coating after 16 weeks' subcutaneous implantation in rats maintained ~55% of its original thickness and presented a homogeneously flat surface demonstrating surface erosion, in contrast to the PCL coated control, which exhibited non-uniform bulk erosion. The Mg alloy coated with PTMC showed less volume reduction and fewer corrosion products as compared to the controls after 52 weeks in vivo. Excessive inflammation, necrosis and hydrogen gas accumulation were not observed. The homogeneous surface erosion of the PTMC coating from exterior to interior (surface-eroding behavior) and its charge neutral degradation products contribute to its excellent protective performance. It is concluded that PTMC is a promising candidate for a surface-eroding coating applied to Mg-based implants.", "conclusion": "The homogeneous surface erosion of the PTMC coating from exterior to interior (surface-eroding behavior) and its charge neutral degradation products contribute to its excellent protective performance. It is concluded that PTMC is a promising candidate for a surface-eroding coating applied to Mg-based implants." }, { "pmid": "23457571", "year": 2013, "title": "Amide proton solvent protection in amylin fibrils probed by quenched hydrogen exchange NMR.", "title_en": null, "title_de": "Lösungsmittelschutz von Amidprotonen in Amylin-Fibrillen, untersucht mittels gequenchter Wasserstoffaustausch-NMR.", "journal": "PloS one", "authors": "Alexandrescu", "author_search": "alexandrescu alexandrescu", "doi": "10.1371/journal.pone.0056467", "doi_url": "https://doi.org/10.1371/journal.pone.0056467", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/23457571/", "url": "https://h2medicine.org/studies/study-alexandrescu-2013-amide-proton-solvent-protection/", "methods": [ "unspecified" ], "indications": [ "diabetes" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2013 · Alexandrescu — Amide proton solvent protection in amylin fibrils probed by quenched hydrogen exchange NMR.", "summary": "This structural biology study used hydrogen-deuterium exchange NMR spectroscopy to map the secondary structure of amylin (a hormone that forms amyloid plaques in type 2 diabetes) inside protein fibrils. „Hydrogen“ in this study refers to hydrogen atoms in protein bonds used as a structural analysis tool — not to molecular hydrogen (H₂) as a therapeutic agent. This paper is not a hydrogen therapy study.", "assessment": "This is a structural biology / biophysics study entirely unrelated to molecular hydrogen therapy. The word „hydrogen“ refers to hydrogen atoms in protein backbone bonds — a standard NMR spectroscopy technique. Honest note: this paper appears in this database due to keyword overlap (the term „hydrogen exchange“). It has no relevance to H₂ therapy, H₂-rich water, or any clinical hydrogen application. The research itself is of interest for understanding amyloid formation in type 2 diabetes, but readers seeking H₂ therapy evidence will not find it here.", "abstract": "Amylin is an endocrine hormone that accumulates in amyloid plaques in patients with advanced type 2 diabetes. The amyloid plaques have been implicated in the destruction of pancreatic β-cells, which synthesize amylin and insulin. To better characterize the secondary structure of amylin in amyloid fibrils we assigned the NMR spectrum of the unfolded state in 95% DMSO and used a quenched hydrogen-deuterium exchange technique to look at amide proton solvent protection in the fibrils. In this technique, partially exchanged fibrils are dissolved in 95% DMSO and information about amide proton occupancy in the fibrils is determined from DMSO-denatured monomers. Hydrogen exchange lifetimes at pH 7.6 and 37°C vary between ∼5 h for the unstructured N-terminus to 600 h for amide protons in the two β-strands that form inter-molecular hydrogen bonds between amylin monomers along the length of the fibril. Based on the protection data we conclude that residues A8-H18 and I26-Y37 comprise the two β-strands in amylin fibrils. There is variation in protection within the β-strands, particularly for strand β1 where only residues F15-H18 are strongly protected. Differences in protection appear to be due to restrictions on backbone dynamics imposed by the packing of two-layers of C2-symmetry-related β-hairpins in the protofilament structure, with strand β1 positioned on the surface and β2 in the interior.", "conclusion": "There is variation in protection within the β-strands, particularly for strand β1 where only residues F15-H18 are strongly protected. Differences in protection appear to be due to restrictions on backbone dynamics imposed by the packing of two-layers of C2-symmetry-related β-hairpins in the protofilament structure, with strand β1 positioned on the surface and β2 in the interior." }, { "pmid": "22537465", "year": 2012, "title": "Molecular hydrogen and radiation protection", "title_en": null, "title_de": "Molekularer Wasserstoff und Strahlenschutz", "journal": "Free Radical Research", "authors": "Chuai et al.", "author_search": "chuai chuai", "doi": "10.3109/10715762.2012.689429", "doi_url": "https://doi.org/10.3109/10715762.2012.689429", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/22537465/", "url": "https://h2medicine.org/studies/study-chuai-2012-radiation-protection/", "methods": [ "drinking-hrw" ], "indications": [ "cancer", "oxidative-stress", "liver", "fundamentals" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2012 · Chuai — Molecular hydrogen and radiation protection", "summary": "Hydrogen (H₂) as radiation protection: ionizing radiation damages cells mainly via the hydroxyl radical (•OH) — exactly the radical H₂ selectively scavenges. This review summarizes that H₂ protects irradiated cells and animals; in a randomized, placebo-controlled study, drinking H₂ water also improved the quality of life of patients undergoing radiotherapy for liver tumors. (Free Radical Research, 2012.)", "assessment": "The review is relevant because it cleanly links the mechanism (•OH scavenging) with a clinical field of application (radiotherapy side effects) and cites a genuine human RCT. For us it is especially interesting that the cited human study used orally consumed H₂ water — the consumption form matching our products. Nevertheless caution in communication: this concerns quality of life under cancer radiotherapy, a highly sensitive medical field — no cure or cancer-therapy promises may be derived from it. Limitations, stated honestly: it is a review (evidence level 4, secondary source, largely populated by the author group itself), the underlying human evidence is a single small RCT, and a possible interest bias of the reporting group cannot be ruled out.", "abstract": "Molecular hydrogen (dihydrogen, H(2)) acts as a therapeutic antioxidant by selectively reducing hydroxyl radicals (•OH) and peroxynitrite (ONOO-). It has been well-known that ionising radiation (IR) causes oxidative damage and consequent apoptosis mainly due to the production of •OH that follows radiolysis of H(2)O. Our department reported the protective effect of H(2) in irradiated cells and mice for the first time, and this effect is well repeated by us and another laboratory in different experimental animal models. A randomised, placebo-controlled investigation also showed consumption of H(2) can improve the quality of life of patients treated with radiotherapy for liver tumours. These encouraging results suggested that H(2) has a potential as a radioprotective agent with efficacy and non-toxicity.", "conclusion": "A randomised, placebo-controlled investigation also showed consumption of H(2) can improve the quality of life of patients treated with radiotherapy for liver tumours. These encouraging results suggested that H(2) has a potential as a radioprotective agent with efficacy and non-toxicity." }, { "pmid": "22965001", "year": 2012, "title": "Proton reduction to hydrogen in biological and chemical systems.", "title_en": null, "title_de": "Protonenreduktion zu Wasserstoff in biologischen und chemischen Systemen.", "journal": "Physical chemistry chemical physics : PCCP", "authors": "Tran et al.", "author_search": "tran tran", "doi": "10.1039/c2cp42413d", "doi_url": "https://doi.org/10.1039/c2cp42413d", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/22965001/", "url": "https://h2medicine.org/studies/study-tran-2012-proton-reduction-biological-chemical/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2012 · Tran et al. — Proton reduction to hydrogen in biological and chemical systems.", "summary": "This chemistry review examines the enzymes (hydrogenases) that biological systems use to produce molecular hydrogen (H₂) from protons, and how these natural catalysts inspire the design of synthetic catalysts for solar-energy-driven H₂ production. This is a biochemistry and green-energy review — not a study of H₂ as a medical or therapeutic agent.", "assessment": "This is a biochemistry and green-energy review — not a hydrogen medicine or therapy review. It describes the biological production of H₂ by hydrogenase enzymes and how this knowledge informs synthetic catalyst design. Honest note: while there is conceptual overlap with H₂ biology (gut H₂ production, bioenergetics), this paper does not address H₂ therapy, H₂-rich water, or health effects. Readers seeking therapeutic H₂ evidence will not find it here. The science is solid and relevant to renewable energy and bioinorganic chemistry.", "abstract": "In the drive to devise catalytic systems to convert solar energy into the energy of chemical bonds, chemists and electrochemists are seeking inspiration from our understanding of enzymes involved in bioenergetics. This is particularly true for generating molecular hydrogen from high energy electrons derived from solar driven water splitting. In this case the natural enzymes are the [NiFe]- and [FeFe]-hydrogenases. In this article we review our present understanding of the structure and mechanistic functioning of these enzymes and how they are providing a blue print to the design and understanding of the mechanism of a variety of synthesized catalysts for proton reduction chemistry.", "conclusion": "In this case the natural enzymes are the [NiFe]- and [FeFe]-hydrogenases. In this article we review our present understanding of the structure and mechanistic functioning of these enzymes and how they are providing a blue print to the design and understanding of the mechanism of a variety of synthesized catalysts for proton reduction chemistry." }, { "pmid": "22720117", "year": 2012, "title": "Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases.", "title_en": null, "title_de": "Molekularer Wasserstoff als aufkommendes therapeutisches medizinisches Gas für neurodegenerative und andere Erkrankungen.", "journal": "Oxidative medicine and cellular longevity", "authors": "Ohno et al.", "author_search": "ohno ohno", "doi": "10.1155/2012/353152", "doi_url": "https://doi.org/10.1155/2012/353152", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/22720117/", "url": "https://h2medicine.org/studies/study-ohno-2012-emerging-therapeutic-medical-neurodegenerative/", "methods": [ "drinking-hrw" ], "indications": [ "diabetes", "metabolic", "liver", "neurology", "cardiovascular", "cancer", "respiratory", "kidney-dialysis", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2012 · Ohno et al. — Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases.", "summary": "This review surveys the research on molecular hydrogen (H₂) across 63 disease models and human diseases documented in the four and a half years after the landmark 2007 Nature Medicine paper. Most evidence comes from rodent studies; six human diseases have been studied including type 2 diabetes, metabolic syndrome, and hemodialysis. The review honestly notes two unresolved puzzles: the absence of a dose-response relationship and the paradoxical efficacy of tiny amounts of H₂ against a large background of gut-derived H₂.", "assessment": "A key review paper for anyone entering the H₂ medical field — it provides both an honest breadth survey and intellectual honesty about unresolved mechanistic questions. The 63 disease models catalogued are predominantly rodent studies, and the human evidence (6 diseases) is preliminary in size and scope. Important limitations: as a review, it does not produce new effect estimates; the mechanistic paradoxes it names (no dose-response, efficacy vs. endogenous H₂ background) remain open questions even today. The review comes from Japan, where the H₂ research field was most active, and should be read with awareness that the field had a positive-publication bias at this stage.", "abstract": "Effects of molecular hydrogen on various diseases have been documented for 63 disease models and human diseases in the past four and a half years. Most studies have been performed on rodents including two models of Parkinson's disease and three models of Alzheimer's disease. Prominent effects are observed especially in oxidative stress-mediated diseases including neonatal cerebral hypoxia; Parkinson's disease; ischemia/reperfusion of spinal cord, heart, lung, liver, kidney, and intestine; transplantation of lung, heart, kidney, and intestine. Six human diseases have been studied to date: diabetes mellitus type 2, metabolic syndrome, hemodialysis, inflammatory and mitochondrial myopathies, brain stem infarction, and radiation-induced adverse effects. Two enigmas, however, remain to be solved. First, no dose-response effect is observed. Rodents and humans are able to take a small amount of hydrogen by drinking hydrogen-rich water, but marked effects are observed. Second, intestinal bacteria in humans and rodents produce a large amount of hydrogen, but an addition of a small amount of hydrogen exhibits marked effects. Further studies are required to elucidate molecular bases of prominent hydrogen effects and to determine the optimal frequency, amount, and method of hydrogen administration for each human disease.", "conclusion": "Second, intestinal bacteria in humans and rodents produce a large amount of hydrogen, but an addition of a small amount of hydrogen exhibits marked effects. Further studies are required to elucidate molecular bases of prominent hydrogen effects and to determine the optimal frequency, amount, and method of hydrogen administration for each human disease." }, { "pmid": "22585131", "year": 2012, "title": "Contributions of the microbial hydrogen economy to colonic homeostasis.", "title_en": null, "title_de": "Beiträge des mikrobiellen Wasserstoffhaushalts zur kolischen Homöostase.", "journal": "Nature reviews. Gastroenterology & hepatology", "authors": "Carbonero et al.", "author_search": "carbonero carbonero", "doi": "10.1038/nrgastro.2012.85", "doi_url": "https://doi.org/10.1038/nrgastro.2012.85", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/22585131/", "url": "https://h2medicine.org/studies/study-carbonero-2012-contributions-microbial-economy-colonic/", "methods": [ "inhalation" ], "indications": [ "cancer", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2012 · Carbonero et al. — Contributions of the microbial hydrogen economy to colonic homeostasis.", "summary": "This review from Nature Reviews Gastroenterology & Hepatology examines how H₂ produced by gut bacteria — as part of the colonic „hydrogen economy“ — affects colonic health, breath-gas diagnostics (lactose intolerance, SIBO, IBS), and the balance between potentially protective and harmful gas species (H₂, methane, hydrogen sulphide). This is a review of endogenous gut H₂ biology, not of administered molecular hydrogen therapy.", "assessment": "A high-quality review in a leading gastroenterology journal, providing the biological context for understanding why H₂ has physiological relevance in the gut. It does not test or endorse exogenous H₂ administration as a therapy; rather, it maps the ecology of endogenous H₂ metabolism. Relevance to H₂ medicine: important background for understanding how gut-derived H₂ may already contribute to colonic antioxidant defence — and why adding small amounts of exogenous H₂ (e.g., via H₂-rich water) might produce biological effects even against a high endogenous H₂ background. This review does not provide evidence for therapeutic H₂ administration, but establishes physiological plausibility.", "abstract": "Colonic gases are among the most tangible features of digestion, yet physicians are typically unable to offer long-term relief from clinical complaints of excessive gas. Studies characterizing colonic gases have linked changes in volume or composition with bowel disorders and shown hydrogen gas (H(2)), methane, hydrogen sulphide, and carbon dioxide to be by-products of the interplay between H(2)-producing fermentative bacteria and H(2) consumers (reductive acetogens, methanogenic archaea and sulphate-reducing bacteria [SRB]). Clinically, H(2) and methane measured in breath can indicate lactose and glucose intolerance, small intestinal bacterial overgrowth and IBS. Methane levels are increased in patients with constipation or IBS. Hydrogen sulphide is a by-product of H(2) metabolism by SRB, which are ubiquitous in the colonic mucosa. Although higher hydrogen sulphide and SRB levels have been detected in patients with IBD, and to a lesser extent in colorectal cancer, this colonic gas might have beneficial effects. Moreover, H(2) has been shown to have antioxidant properties and, in the healthy colon, physiological H(2) concentrations might protect the mucosa from oxidative insults, whereas an impaired H(2) economy might facilitate inflammation or carcinogenesis. Therefore, standardized breath gas measurements combined with ever-improving molecular methodologies could provide novel strategies to prevent, diagnose or manage numerous colonic disorders.", "conclusion": "Moreover, H(2) has been shown to have antioxidant properties and, in the healthy colon, physiological H(2) concentrations might protect the mucosa from oxidative insults, whereas an impaired H(2) economy might facilitate inflammation or carcinogenesis. Therefore, standardized breath gas measurements combined with ever-improving molecular methodologies could provide novel strategies to prevent, dia" }, { "pmid": "21621588", "year": 2012, "title": "Molecular hydrogen is a novel antioxidant to efficiently reduce oxidative stress with potential for the improvement of mitochondrial diseases.", "title_en": null, "title_de": "Molekularer Wasserstoff ist ein neuartiges Antioxidans zur effizienten Reduktion von oxidativem Stress mit Potenzial für die Verbesserung mitochondrialer Erkrankungen.", "journal": "Biochimica et biophysica acta", "authors": "Ohta", "author_search": "ohta ohta", "doi": "10.1016/j.bbagen.2011.05.006", "doi_url": "https://doi.org/10.1016/j.bbagen.2011.05.006", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/21621588/", "url": "https://h2medicine.org/studies/study-ohta-2012-antioxidant-efficiently-reduce-oxidative/", "methods": [ "inhalation", "saline-iv", "bath-topical", "drinking-hrw" ], "indications": [ "cancer", "skin-aging", "eye", "immune-system", "allergy", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2012 · Ohta — Molecular hydrogen is a novel antioxidant to efficiently reduce oxidative stress with potential for the improvement of mitochondrial diseases.", "summary": "This review by Shigeo Ohta — one of the founders of modern H₂ medicine — surveys the biological effects of molecular hydrogen across more than 38 diseases, physiological states, and clinical tests documented in the years following the 2007 Nature Medicine paper. It covers multiple administration routes (inhalation, H₂-rich water, H₂ bath, H₂ saline, eye drops), reports anti-oxidative, anti-inflammatory, and anti-allergic effects, and highlights preliminary clinical evidence that H₂-dissolved water may benefit mitochondrial disorders.", "assessment": "A foundational review from one of the field's leading researchers, providing a comprehensive picture of where H₂ medicine stood around 2011–2012. Its value is in the breadth of evidence surveyed and its honest acknowledgment of mechanistic gaps. Limitations: as a review (not original data), it does not provide new effect estimates; the majority of evidence it surveys is preclinical (animal/in-vitro); the six human disease areas covered had very small, often non-randomised preliminary trials at that stage. The review's conclusion that H₂ has „great potential for actual medical applications“ is warranted as a hypothesis, but should not be read as established clinical evidence. Since 2012, the evidence base has grown — this review should be treated as a historical anchor point, not the current state of the field.", "abstract": "BACKGROUND: Mitochondria are the major source of oxidative stress. Acute oxidative stress causes serious damage to tissues, and persistent oxidative stress is one of the causes of many common diseases, cancer and the aging process; however, there has been little success in developing an effective antioxidant with no side effect. We have reported that molecular hydrogen has potential as an effective antioxidant for medical applications [Ohsawa et al., Nat. Med. 13 (2007) 688-694]. SCOPE OF REVIEW: We review the recent progress toward therapeutic and preventive applications of hydrogen. Since we published the first paper in Nature Medicine, effects of hydrogen have been reported in more than 38 diseases, physiological states and clinical tests in leading biological/medical journals. Based on this cumulative knowledge, the beneficial biological effects of hydrogen have been confirmed. There are several ways to intake or consume hydrogen, including inhaling hydrogen gas, drinking hydrogen-dissolved water, taking a hydrogen bath, injecting hydrogen-dissolved saline, dropping hydrogen-dissolved saline into the eyes, and increasing the production of intestinal hydrogen by bacteria. Hydrogen has many advantages for therapeutic and preventive applications, and shows not only anti-oxidative stress effects, but also has various anti-inflammatory and anti-allergic effects. Preliminary clinical trials show that drinking hydrogen-dissolved water seems to improve the pathology of mitochondrial disorders. MAJOR CONCLUSIONS: Hydrogen has biological benefits toward preventive and therapeutic applications; however, the molecular mechanisms underlying the marked effects of small amounts of hydrogen remain elusive. GENERAL SIGNIFICANCE: Hydrogen is a novel antioxidant with great potential for actual medical applications. This article is part of a Special Issue entitled Biochemistry of Mitochondria.", "conclusion": "Hydrogen has biological benefits toward preventive and therapeutic applications; however, the molecular mechanisms underlying the marked effects of small amounts of hydrogen remain elusive. GENERAL" }, { "pmid": "23079742", "year": 2012, "title": "Binding hot-spots in an antibody-ssDNA interface: a molecular dynamics study.", "title_en": null, "title_de": "Bindungs-Hotspots in einer Antikörper-ssDNA-Grenzfläche: eine molekulardynamische Studie.", "journal": "Molecular bioSystems", "authors": "Wang et al.", "author_search": "wang wang", "doi": "10.1039/c2mb25250c", "doi_url": "https://doi.org/10.1039/c2mb25250c", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/23079742/", "url": "https://h2medicine.org/studies/study-wang-2012-binding-hot-spots-antibody/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2012 · Wang et al. — Binding hot-spots in an antibody-ssDNA interface: a molecular dynamics study.", "summary": "This computational biology study used molecular dynamics simulations to identify key amino acid residues that stabilise the interaction between a lupus-associated antibody and single-stranded DNA (ssDNA). „Hydrogen“ in this study refers exclusively to hydrogen bonds between protein residues and DNA — the fundamental structural force in molecular biology. This is not a molecular hydrogen (H₂) therapy study.", "assessment": "This is a computational structural biology study with no connection to molecular hydrogen therapy. The term „molecular hydrogen bonds“ refers to classical H-bond interactions in protein-DNA interfaces — unrelated to H₂ gas or its biological or medical effects. Honest note: this paper is indexed here due to keyword overlap. Its findings are relevant to lupus autoantibody biology and protein engineering, not to H₂ medicine.", "abstract": "Simulating antigen-antibody interactions is essential for elucidating antigen-antibody mechanics. Proteins interactions are vital for elucidating antibody-ssDNA associations in immunology. Therefore, this study investigated the dissociation of the human systemic lupus erythematosus antibody-ssDNA complex structure. Dissociation (i.e. the distance between the center of mass of the ssDNA and the antibody) is also studied using the potential of mean force calculations based on molecular dynamics and the explicit water model. The MM-PBSA method is also used to prove our dissociation simulations. With 605 nanosecond molecular dynamics simulations, the results indicate that the 8 residues (i.e. Gly44 (HCDR2), Asn54 (HCDR2), Arg98 (HCDR3), Tyr100 (HCDR3), Asp101 (HCDR3), Tyr32 (LCDR1), Tyr49 (LCDR2) and Asn50 (LCDR2)), and the five inter-protein molecular hydrogen bonds may profoundly impact the antibody-ssDNA interaction, a finding which may be useful for protein engineering of this antibody-ssDNA structure. Experimental binding affinity of this antibody-ssDNA complex equals 7.00 kcal mol(-1). Our dissociation binding affinity is 7.96 ± 0.33 kcal mol(-1) and MM-PBSA binding affinity is 9.12 ± 1.65 kcal mol(-1), which is close to the experimental value. Additionally, the 8 residues Gly44 (HCDR2), Asn54 (HCDR2), Arg98 (HCDR3), Tyr100 (HCDR3), Asp101 (HCDR3), Tyr32 (LCDR1), Tyr49 (LCDR2) and Asn50 (LCDR2) may play a more significant role in developing bioactive antibody analogues.", "conclusion": "Our dissociation binding affinity is 7.96 ± 0.33 kcal mol(-1) and MM-PBSA binding affinity is 9.12 ± 1.65 kcal mol(-1), which is close to the experimental value. Additionally, the 8 residues Gly44 (HCDR2), Asn54 (HCDR2), Arg98 (HCDR3), Tyr100 (HCDR3), Asp101 (HCDR3), Tyr32 (LCDR1), Tyr49 (LCDR2) and Asn50 (LCDR2) may play a more significant role in developing bioactive antibody analogues." }, { "pmid": "23014490", "year": 2012, "title": "A hydrogen gas-water equilibration method produces accurate and precise stable hydrogen isotope ratio measurements in nutrition studies.", "title_en": null, "title_de": "Eine Wasserstoffgas-Wasser-Äquilibrierungsmethode liefert genaue und präzise Messungen stabiler Wasserstoff-Isotopenverhältnisse in Ernährungsstudien.", "journal": "The Journal of nutrition", "authors": "Wong et al.", "author_search": "wong wong", "doi": "10.3945/jn.112.167957", "doi_url": "https://doi.org/10.3945/jn.112.167957", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/23014490/", "url": "https://h2medicine.org/studies/study-wong-2012-equilibration-method-produces-accurate/", "methods": [ "inhalation" ], "indications": [ "metabolic", "neurology" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2012 · Wong et al. — A hydrogen gas-water equilibration method produces accurate and precise stable hydrogen isotope ratio measurements in nutrition studies.", "summary": "This analytical chemistry study validated a platinum-catalysed hydrogen gas–water equilibration method for measuring stable hydrogen isotope ratios (deuterium) in body fluids — used in nutrition research to measure body composition and energy expenditure. „Hydrogen gas“ here is H₂ used as an analytical reagent, not as a therapeutic agent. This is a measurement methodology paper, not an H₂ therapy study.", "assessment": "This is an analytical chemistry / nutrition measurement methodology paper with no relevance to molecular hydrogen therapy. H₂ gas is used as an analytical reagent for isotope ratio mass spectrometry — not as a substance administered to people for health effects. Honest note: this paper is catalogued here due to H₂ keyword overlap. It does not provide any evidence for or against therapeutic H₂ applications. Its contribution is to nutrition science measurement methodology.", "abstract": "Stable hydrogen isotope methodology is used in nutrition studies to measure growth, breast milk intake, and energy requirement. Isotope ratio MS is the best instrumentation to measure the stable hydrogen isotope ratios in physiological fluids. Conventional methods to convert physiological fluids to hydrogen gas (H(2)) for mass spectrometric analysis are labor intensive, require special reagent, and involve memory effect and potential isotope fractionation. The objective of this study was to determine the accuracy and precision of a platinum catalyzed H(2)-water equilibration method for stable hydrogen isotope ratio measurements. Time to reach isotopic equilibrium, day-to-day and week-to-week reproducibility, accuracy, and precision of stable hydrogen isotope ratio measurements by the H(2)-water equilibration method were assessed using a Thermo DELTA V Advantage continuous-flow isotope ratio mass spectrometer. It took 3 h to reach isotopic equilibrium. The day-to-day and week-to-week measurements on water and urine samples with natural abundance and enriched levels of deuterium were highly reproducible. The method was accurate to within 2.8 (o)/oo and reproducible to within 4.0 (o)/oo based on analysis of international references. All the outcome variables, whether in urine samples collected in 10 doubly labeled water studies or plasma samples collected in 26 body water studies, did not differ from those obtained using the reference zinc reduction method. The method produced highly accurate estimation on ad libitum energy intakes, body composition, and water turnover rates. The method greatly reduces the analytical cost and could easily be adopted by laboratories equipped with a continuous-flow isotope ratio mass spectrometer.", "conclusion": "The method produced highly accurate estimation on ad libitum energy intakes, body composition, and water turnover rates. The method greatly reduces the analytical cost and could easily be adopted by laboratories equipped with a continuous-flow isotope ratio mass spectrometer." }, { "pmid": "22797884", "year": 2012, "title": "Evidence for the preservation of native inter- and intra-molecular hydrogen bonds in the desolvated FK-binding protein·FK506 complex produced by electrospray ionization.", "title_en": null, "title_de": "Nachweis der Erhaltung nativer inter- und intramolekularer Wasserstoffbrückenbindungen im desolvatisierten FK-Bindungsprotein·FK506-Komplex, erzeugt durch Elektrospray-Ionisation.", "journal": "Journal of the American Society for Mass Spectrometry", "authors": "Hopper et al.", "author_search": "hopper hopper", "doi": "10.1007/s13361-012-0430-y", "doi_url": "https://doi.org/10.1007/s13361-012-0430-y", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/22797884/", "url": "https://h2medicine.org/studies/study-hopper-2012-evidence-preservation-native-inter/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2012 · Hopper et al. — Evidence for the preservation of native inter- and intra-molecular hydrogen bonds in the desolvated FK-binding protein·FK506 complex produced by electrospray ionization.", "summary": "This biophysical study used mass spectrometry and ion mobility spectrometry to investigate whether protein-ligand hydrogen bonds are preserved when protein complexes are transferred from solution into the gas phase by electrospray ionisation. „Hydrogen bonds“ here refers to structural inter-atomic bonds in proteins — not to molecular hydrogen (H₂) gas or therapy. This paper has no connection to H₂ medicine.", "assessment": "This is a biophysics / native mass spectrometry methodology paper with no relevance to molecular hydrogen therapy. The term „hydrogen bonds“ refers to the fundamental structural interactions between electronegative atoms and hydrogen within proteins — standard physical chemistry. Honest note: this paper is catalogued here due to keyword overlap (\"hydrogen bonds\"). It contributes to native mass spectrometry methodology and protein structural biology, not to H₂ medicine.", "abstract": "It is now well established that electrospray ionization (ESI) is capable of introducing noncovalent protein assemblies into a desolvated environment, thereby allowing their analysis by mass spectrometry. The degree to which native interactions from the solution phase are preserved in this environment is less clear. Site-directed mutagenesis of FK506-binding protein (FKBP) has been employed to probe specific intra- and inter-molecular interactions within the complex between FKBP and its ligand FK506. Collisional activation of wild-type and mutant-FKBP•FK506 ions, generated by ESI, demonstrated that removal of native protein-ligand interactions formed between residues Asp37, Tyr82, and FK506 significantly destabilized the complex. Mutation of Arg42 to Ala42, or Tyr26 to Phe26 also resulted in lower energy dissociation of the FKBP·FK506 complex. Although these residues do not form direct H-bonds to FK506, they interact with Asp37, ensuring its correct orientation to associate with the ligand. Comparison with solution-based affinity measurements of these mutants has been discussed, including the stabilization afforded by ordered water molecules. Ion mobility spectrometry (IMS) has been employed to provide gas-phase structural information on the unfolding of the complexes. The [M + 6H](6+) complexes of the wild-type and mutants have been shown to resist unfolding and retain compact conformations. However, removal of the basic Arg42 residue was found to induce significant structural weakening of the [M + 7H](7+) complex when raised to dissociation-level energies. Overall, destabilization of the FKBP·FK506 complex, resulting from targeted removal of specific H-bonds, provides evidence for the preservation of these interactions in the desolvated wild-type complex.", "conclusion": "However, removal of the basic Arg42 residue was found to induce significant structural weakening of the [M + 7H](7+) complex when raised to dissociation-level energies. Overall, destabilization of the FKBP·FK506 complex, resulting from targeted removal of specific H-bonds, provides evidence for the preservation of these interactions in the desolvated wild-type complex." }, { "pmid": "22687834", "year": 2012, "title": "Hydrogen may inhibit collagen-induced platelet aggregation: an ex vivo and in vivo study.", "title_en": null, "title_de": "Wasserstoff könnte die kollageninduzierte Thrombozytenaggregation hemmen: eine Ex-vivo- und In-vivo-Studie.", "journal": "Internal medicine (Tokyo, Japan)", "authors": "Takeuchi et al.", "author_search": "takeuchi takeuchi", "doi": "10.2169/internalmedicine.51.7161", "doi_url": "https://doi.org/10.2169/internalmedicine.51.7161", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/22687834/", "url": "https://h2medicine.org/studies/study-takeuchi-2012-may-inhibit-collagen-induced/", "methods": [ "inhalation", "saline-iv" ], "indications": [ "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2012 · Takeuchi et al. — Hydrogen may inhibit collagen-induced platelet aggregation: an ex vivo and in vivo study.", "summary": "In this mixed-design study — combining human ex vivo blood tests and rat in vivo experiments — molecular hydrogen (via H₂ saline or H₂ inhalation) significantly inhibited collagen-induced platelet aggregation. Platelet aggregation is a key step in blood clot formation; reduced aggregation could, in principle, be relevant to cardiovascular protection. However, this is a preclinical and ex vivo study; clinical implications for humans remain unproven.", "assessment": "An interesting preclinical and ex vivo study with a modest human blood component (n = 6 ex vivo). The finding that H₂ may reduce platelet aggregation is novel and mechanistically plausible — this has potential relevance for cardiovascular research. Honest limitations: the human component is ex vivo (outside the body, no clinical endpoints), the rat experiments use very small groups, and there is no assessment of safety (bleeding risk from reduced platelet aggregation). This remains an early-stage, hypothesis-generating study. Clinical translation would require randomised controlled trials with cardiovascular endpoints and safety monitoring.", "abstract": "OBJECTIVE: Hydrogen selectively reduces hydroxyl radicals and peroxynitrite, and numerous experimental and clinical studies suggest that hydrogen can exert potent cellular protective effects against a wide variety of diseases. Furthermore, there is increasing evidence that antioxidants can modulate platelet activation. The aim of the present study was to investigate the relationship between hydrogen and collagen-induced platelet aggregation. METHODS: For human ex vivo studies, we collected blood samples from six healthy humans and added normal saline or hydrogen-rich saline to blood and platelet-rich plasma. We found that collagen (1 µg/mL)-induced platelet aggregation was significantly inhibited by hydrogen-rich saline compared with a normal saline group (p=0.044). For rat in vivo studies, animals (n=17) were exposed to either nitrogen-based mixed gas with hydrogen (H2 gas group; n=9) or without hydrogen (non-H2 gas group; n=8). Additionally, another animals (n=13) administered either normal (NS group; n=7) or hydrogen-rich saline (HS group; n=6) (5 ml/kg) via intravenous infusion. Blood samples were drawn from the vena cava before treatment and from the right ventricle after treatment. Collagen (12 µg/mL)-induced platelet aggregation was then measured. RESULTS: Collagen-induced platelet aggregation was significantly decreased in H2 gas and HS group rats (p=0.042, 0.018, respectively), while there was no difference in non-H2 gas and NS group rats before and after treatment. CONCLUSION: In summary, these data suggest that hydrogen may inhibit collagen-induced platelet aggregation.", "conclusion": "In summary, these data suggest that hydrogen may inhibit collagen-induced platelet aggregation." }, { "pmid": "22648259", "year": 2012, "title": "Hydrogen therapy may be an effective and specific novel treatment for aplastic anemia.", "title_en": null, "title_de": "Die Wasserstofftherapie könnte eine wirksame und spezifische neuartige Behandlung für aplastische Anämie sein.", "journal": "Medical science monitor : international medical journal of experimental and clinical research", "authors": "Qian et al.", "author_search": "qian qian", "doi": "10.12659/msm.882886", "doi_url": "https://doi.org/10.12659/msm.882886", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/22648259/", "url": "https://h2medicine.org/studies/study-qian-2012-may-effective-specific-aplastic/", "methods": [ "inhalation" ], "indications": [ "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2012 · Qian et al. — Hydrogen therapy may be an effective and specific novel treatment for aplastic anemia.", "summary": "Aplastic anemia is a severe bone marrow failure disease with high mortality — and oxidative stress and inflammatory cytokines like TNF-α and IL-6 play a central role in its development. This theoretical paper proposes that molecular hydrogen (H₂), with its documented ability to selectively neutralize toxic oxygen radicals and suppress pro-inflammatory cytokines, could be a novel therapeutic approach to aplastic anemia. The authors present this as a hypothesis grounded in mechanistic reasoning, not a clinical study.", "assessment": "This is a theoretical hypothesis paper — no animal model, no cell experiments, no patients. It proposes that H₂ could be useful in aplastic anemia based on mechanistic reasoning about oxidative stress and cytokine suppression. While the logic is coherent, no clinical or preclinical evidence for this specific indication is provided. The paper should be read as a research proposal, not as evidence of efficacy. Future experimental validation would be needed before any therapeutic conclusions can be drawn.", "abstract": "Aplastic anemia (AA) is a rare bone marrow failure disorder with high mortality rate, which is characterized by pancytopenia and an associated increase in the risk of hemorrhage, infection, organ dysfunction and death. The oxidation phenomenon and/or the formation of free radicals have been suggested to be causally related to various hematological disorders, including aplastic anemia. TNF-α, IL-6, and IL-2 also play important roles in the pathogenesis of AA. Recent studies have provided evidence that hydrogen inhalation can selectively reduce cytotoxic oxygen radicals and exert antioxidant effects. It was also reported that hydrogen could suppress the levels of TNF-α and IL-6. Based on these findings, we hypothesize that hydrogen therapy may be an effective, simple, economic and novel strategy in the treatment of aplastic anemia.", "conclusion": "It was also reported that hydrogen could suppress the levels of TNF-α and IL-6. Based on these findings, we hypothesize that hydrogen therapy may be an effective, simple, economic and novel strategy in the treatment of aplastic anemia." }, { "pmid": "22560529", "year": 2012, "title": "Serum alkalinization and hydrogen-rich water in healthy men.", "title_en": null, "title_de": "Serumalkalisierung und wasserstoffreiches Wasser bei gesunden Männern.", "journal": "Mayo Clinic proceedings", "authors": "Ostojic", "author_search": "ostojic ostojic", "doi": "10.1016/j.mayocp.2012.02.008", "doi_url": "https://doi.org/10.1016/j.mayocp.2012.02.008", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/22560529/", "url": "https://h2medicine.org/studies/study-ostojic-2012-serum-alkalinization-healthy-men/", "methods": [ "drinking-hrw" ], "indications": [ "other" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2012 · Ostojic — Serum alkalinization and hydrogen-rich water in healthy men.", "summary": "This publication investigates serum alkalinization effects of hydrogen-rich water in healthy men. The full abstract was not available in the source data. For detailed methodology and results, please refer to the original article via DOI: 10.1016/j.mayocp.2012.02.008 (Mayo Clinic Proceedings, 2012).", "assessment": "No abstract was available for this entry. No findings, effect sizes, or conclusions can be reported or inferred. The study is listed in Mayo Clinic Proceedings (evidence level 2 as assigned), suggesting a controlled design, but without the abstract or full text, the methodology and results cannot be evaluated. Given the author and journal, this is likely a small controlled study on acid-base effects of HRW. Readers should consult the original via DOI before citing this work.", "abstract": null, "conclusion": null }, { "pmid": "22460088", "year": 2012, "title": "Hydrogen-rich saline protects immunocytes from radiation-induced apoptosis.", "title_en": null, "title_de": "Wasserstoffreiche Kochsalzlösung schützt Immunzellen vor strahlungsinduzierter Apoptose.", "journal": "Medical science monitor : international medical journal of experimental and clinical research", "authors": "Yang et al.", "author_search": "yang yang", "doi": "10.12659/msm.882616", "doi_url": "https://doi.org/10.12659/msm.882616", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/22460088/", "url": "https://h2medicine.org/studies/study-yang-2012-saline-protects-immunocytes-radiation/", "methods": [ "saline-iv" ], "indications": [ "cancer", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2012 · Yang et al. — Hydrogen-rich saline protects immunocytes from radiation-induced apoptosis.", "summary": "Ionizing radiation depletes the immune system by triggering apoptosis (programmed cell death) in immune cells — a major problem in radiation therapy and radiological accidents. This animal and cell study found that hydrogen-rich saline (H₂ dissolved in physiological saline) significantly reduced radiation-induced cell death in immune cells, attenuated the activation of apoptosis enzymes, and helped maintain white blood cell and platelet counts in irradiated mice. These are preclinical findings in mice and cell cultures — not human data.", "assessment": "This is a preclinical study in mice and human cell lines — no human clinical data. The results are mechanistically plausible and consistent with H₂'s known radical-scavenging properties. The combination of in-vitro and in-vivo data strengthens the findings within the preclinical context. However, extrapolation to human radiation therapy patients requires clinical trials, which were not done here. The study is a useful stepping stone for further research on H₂ as a radioprotective agent.", "abstract": "BACKGROUND: Radiation often causes depletion of immunocytes in tissues and blood, which results in immunosuppression. Molecular hydrogen (H2) has been shown in recent studies to have potential as a safe and effective radioprotective agent through scavenging free radicals. This study was designed to test the hypothesis that H2 could protect immunocytes from ionizing radiation (IR). MATERIAL/METHODS: H2 was dissolved in physiological saline or medium using an apparatus produced by our department. A 2-[6-(4'-hydroxy) phenoxy-3H-xanthen-3-on-9-yl] benzoate (HPF) probe was used to detect intracellular hydroxyl radicals (•OH). Cell apoptosis was evaluated by annexin V-FITC and Propidium iodide (PI) staining as well as the caspase 3 activity. Finally, we examined the hematological changes using an automatic Sysmex XE 2100 hematology analyzer. RESULTS: We demonstrated H2-rich medium pretreatment reduced •OH level in AHH-1 cells. We also showed H2 reduced radiation-induced apoptosis in thymocytes and splenocytes in living mice. Radiation-induced caspase 3 activation was also attenuated by H2 treatment. Finally, we found that H2 rescued the radiation-caused depletion of white blood cells (WBC) and platelets (PLT). CONCLUSIONS: This study suggests that H2 protected the immune system and alleviated the hematological injury induced by IR.", "conclusion": "This study suggests that H2 protected the immune system and alleviated the hematological injury induced by IR." }, { "pmid": "22431222", "year": 2012, "title": "Charge-site-dependent dissociation of hydrogen-rich radical peptide cations upon vacuum UV photoexcitation.", "title_en": null, "title_de": "Ladungsstellenabhängige Dissoziation wasserstoffreicher Radikal-Peptidkationen bei Vakuum-UV-Photoanregung.", "journal": "Chemistry (Weinheim an der Bergstrasse, Germany)", "authors": "Madsen et al.", "author_search": "madsen madsen", "doi": "10.1002/chem.201103534", "doi_url": "https://doi.org/10.1002/chem.201103534", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/22431222/", "url": "https://h2medicine.org/studies/study-madsen-2012-charge-site-dependent-dissociation/", "methods": [ "unspecified" ], "indications": [ "skin-aging" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2012 · Madsen et al. — Charge-site-dependent dissociation of hydrogen-rich radical peptide cations upon vacuum UV photoexcitation.", "summary": "This study investigates a highly specialized mass spectrometry technique for analyzing peptide structure — specifically how „hydrogen-rich\" radical peptide ions fragment when excited by vacuum ultraviolet light. The „hydrogen-rich\" in the title refers to a chemical physics concept in peptide fragmentation analysis, not to molecular hydrogen (H₂) as a health-relevant gas. This paper is analytical chemistry research with no biological health application.", "assessment": "This paper is not relevant to H₂ biology or molecular hydrogen health research. The term „hydrogen-rich\" in the title refers to a specific state of peptide radical cations in mass spectrometry, not to molecular hydrogen gas. No conclusions about H₂ therapy, antioxidant effects, or any health application can be drawn from this study. It appears to have been captured in H₂-related literature databases due to keyword overlap. Readers interested in H₂ research should consult studies that directly investigate molecular hydrogen as a bioactive gas.", "abstract": "Here, 193 nm vacuum ultraviolet photodissociation (VUVPD) was used to investigate the fragmentation of hydrogen-rich radical peptide cations generated by electron transfer reactions. VUVPD offers new insight into the factors that drive radical- and photon-directed processes. The location of a basic Arg site influences photon-activated C(α)-C(O) bond cleavages of singly charged peptide radical cations, an outcome attributed to the initial conformation of the peptide as supported by molecular dynamics simulated annealing and the population of excited states upon UV excitation. This hybrid ETD/VUVPD method was employed to identify phosphorylation sites of the kinase domain of human TRPM7/ChaK1.", "conclusion": "The location of a basic Arg site influences photon-activated C(α)-C(O) bond cleavages of singly charged peptide radical cations, an outcome attributed to the initial conformation of the peptide as supported by molecular dynamics simulated annealing and the population of excited states upon UV excitation. This hybrid ETD/VUVPD method was employed to identify phosphorylation sites of the kinase doma" }, { "pmid": "22425564", "year": 2012, "title": "Inhibition of hepatitis C virus NS5A by fluoro-olefin based γ-turn mimetics.", "title_en": null, "title_de": "Hemmung des NS5A-Proteins des Hepatitis-C-Virus durch Fluor-Olefin-basierte γ-Turn-Mimetika.", "journal": "Bioorganic & medicinal chemistry letters", "authors": "Chang et al.", "author_search": "chang chang", "doi": "10.1016/j.bmcl.2012.02.051", "doi_url": "https://doi.org/10.1016/j.bmcl.2012.02.051", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/22425564/", "url": "https://h2medicine.org/studies/study-chang-2012-inhibition-hepatitis-virus-ns5a/", "methods": [ "unspecified" ], "indications": [ "liver" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2012 · Chang et al. — Inhibition of hepatitis C virus NS5A by fluoro-olefin based γ-turn mimetics.", "summary": "This study develops a new class of antiviral compounds targeting the NS5A protein of hepatitis C virus (HCV) — using a fluoro-olefin chemical scaffold to mimic the three-dimensional structure of natural peptide inhibitors. The lead compound showed picomolar potency against HCV in cell-based assays. This is a pure medicinal chemistry / drug discovery study. The connection to hydrogen, if any, is through intramolecular hydrogen bonding as a structural feature in the inhibitor molecules — not molecular H₂ as a health-relevant gas.", "assessment": "This paper is not relevant to molecular hydrogen (H₂) therapy or H₂ biology. It is a medicinal chemistry study on antiviral drug design. The word „hydrogen\" in the abstract refers to intramolecular hydrogen bonds in drug molecules — a structural chemistry concept entirely unrelated to dissolved H₂ gas. No conclusions about H₂ health effects can be drawn from this study. It appears in H₂-related literature databases as an indexing artifact.", "abstract": "The HCV non-structural protein NS5A has been established as a viable target for the development of direct acting antiviral therapy. From computational modeling studies strong intra-molecular hydrogen bonds were found to be a common structural moiety within known NS5A inhibitors that have low pico-molar replicon potency. Efforts to reproduce these γ-turn-like substructures provided a novel NS5A inhibitor based on a fluoro-olefin isostere. This fluoro-olefin containing inhibitor exhibited picomolar activity (EC(50)=79 pM) against HCV genotype 1b replicon without measurable cytotoxicity. This level of activity is comparable to the natural peptide-based inhibitors currently under clinic evaluation, and demonstrates that a peptidomimetic approach can serve as a useful strategy to produce potent and structurally unique inhibitors of HCV NS5A.", "conclusion": "This fluoro-olefin containing inhibitor exhibited picomolar activity (EC(50)=79 pM) against HCV genotype 1b replicon without measurable cytotoxicity. This level of activity is comparable to the natural peptide-based inhibitors currently under clinic evaluation, and demonstrates that a peptidomimetic approach can serve as a useful strategy to produce potent and structurally unique inhibitors of HCV" }, { "pmid": "22390199", "year": 2012, "title": "Hydrogenase: the next antibiotic target?", "title_en": null, "title_de": "Hydrogenase: das nächste Antibiotika-Ziel?", "journal": "Clinical science (London, England : 1979)", "authors": "Nie et al.", "author_search": "nie nie", "doi": "10.1042/cs20110396", "doi_url": "https://doi.org/10.1042/cs20110396", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/22390199/", "url": "https://h2medicine.org/studies/study-nie-2012-hydrogenase-next-antibiotic-target/", "methods": [ "inhalation" ], "indications": [ "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2012 · Nie et al. — Hydrogenase: the next antibiotic target?", "summary": "Bacteria produce hydrogen gas (H₂) via enzymes called hydrogenases — and this review proposes that these enzymes, by generating H₂ which neutralizes bactericidal hydroxyl radicals, may actually help bacteria survive antibiotic treatment and evade immune defenses. If correct, inhibiting bacterial hydrogenases could become a new strategy for antibiotics. This is a review article that synthesizes existing knowledge and presents a speculative hypothesis — no new experiments are conducted.", "assessment": "This is a review paper presenting a speculative hypothesis — no new experimental data are generated. The idea that bacterial hydrogenases could be antibiotic targets is scientifically interesting and mechanistically plausible, but remains unproven. The authors appropriately use cautious language („we speculate\"). This paper does not concern H₂ therapy for humans — it addresses a potential bacterial defense mechanism. The hypothesis would need experimental validation (e.g., hydrogenase knockout bacteria, animal infection models) before any clinical or therapeutic conclusions could be drawn.", "abstract": "The struggle to control infectious diseases has become increasingly difficult due to resistance to current antibiotics and the co-existence of multiplying and non-multiplying bacteria, which makes it an urgent task to discover new antibiotic targets and to develop new antibiotics. Hydrogenases are found in micro-organisms belonging to the archaea and bacteria domains, which can catalyse the reversible oxidation of hydrogen gas (H2↔2H⁺ +2e) and play pleiotropic roles in microbial survival. Studies have shown that H2 is a potent antioxidant and can selectively neutralize OH• (hydroxyl radicals). OH•, however, has been implicated as one of the mechanisms whereby bactericidal antibiotics and professional phagocytes kill bacteria. Thus we have enough reason to speculate that hydrogenases and H2 are conducive to increasing the virulence and antibiotic resistance of bacteria, and hydrogenase inhibitors would help control bacterial infection.", "conclusion": "OH•, however, has been implicated as one of the mechanisms whereby bactericidal antibiotics and professional phagocytes kill bacteria. Thus we have enough reason to speculate that hydrogenases and H2 are conducive to increasing the virulence and antibiotic resistance of bacteria, and hydrogenase inhibitors would help control bacterial infection." }, { "pmid": "22339382", "year": 2012, "title": "Evaluation of outgassing, tear strength, and detail reproduction in alginate substitute materials.", "title_en": null, "title_de": "Bewertung von Ausgasung, Reißfestigkeit und Detailwiedergabe in Alginat-Ersatzmaterialien.", "journal": "Operative dentistry", "authors": "Baxter et al.", "author_search": "baxter baxter", "doi": "10.2341/11-365-l", "doi_url": "https://doi.org/10.2341/11-365-l", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/22339382/", "url": "https://h2medicine.org/studies/study-baxter-2012-outgassing-tear-strength-detail/", "methods": [ "inhalation", "bath-topical" ], "indications": [ "oral-health" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2012 · Baxter et al. — Evaluation of outgassing, tear strength, and detail reproduction in alginate substitute materials.", "summary": "This study compares dental impression materials (alginate substitutes) to traditional alginate for three performance properties: the release of hydrogen gas (outgassing), tear strength, and detail reproduction quality. All tested alginate substitutes showed superior performance to traditional alginate. The „hydrogen\" relevance here is entirely technical: hydrogen gas is released as a byproduct when alginate substitutes react with water, causing surface porosity in dental casts — a problem the study quantifies and evaluates.", "assessment": "This paper is not relevant to molecular hydrogen (H₂) biology or therapy. It is a dental materials science study evaluating impression materials. The „hydrogen\" reference concerns gaseous H₂ released as a chemical byproduct during dental material setting — a materials engineering issue, not a biological or health topic. No conclusions relevant to H₂ health research can be drawn from this study. It appears in H₂ research databases as an indexing artifact based on keyword overlap.", "abstract": "OBJECTIVE: To compare three alginate substitute materials to an alginate impression material for cast surface porosity (outgassing), tear strength, and detail reproduction. MATERIALS AND METHODS: Detail reproduction tests were performed following American National Standards Institute/American Dental Association (ANSI/ADA) Specification No. 19. To measure tear strength, 12 samples of each material were made using a split mold, placed in a water bath until testing, and loaded in tension until failure at a rate of 500 mm/min using a universal testing machine. For cast surface porosity testing, five impressions of a Teflon mold with each material were placed in a water bath (37.8°C) for the in-mouth setting time and poured with vacuum-mixed Silky Rock die stone at 5, 10, 30, and 60 minutes from the start of mixing. The gypsum samples were analyzed with a digital microscope for surface porosity indicative of hydrogen gas release by comparing the surface obtained at each interval with four casts representing no, little, some, and significant porosity. Data analysis was performed using parametric and Kruskal-Wallis analysis of variance (ANOVA), Tukey/Kramer post-hoc tests (α=0.05), and individual Mann-Whitney U tests (α=0.0167). RESULTS: All alginate substitute materials passed the detail reproduction test. Tear strength of the alginate substitute materials was significantly better than alginate and formed three statistically different groups: AlgiNot had the lowest tear strength, Algin-X Ultra had the highest tear strength, and Position Penta Quick had intermediate tear strength. Significant variation in outgassing existed between materials and pouring times (p<0.05). All alginate substitute materials exhibited the least outgassing and cast porosity 60 minutes after mixing. CONCLUSIONS: Detail reproduction and tear strength of alginate substitute materials were superior to traditional alginate. The outgassing effect was minimal for most materials tested. Alginate substitute materials are superior replacements for irreversible hydrocolloid.", "conclusion": "Detail reproduction and tear strength of alginate substitute materials were superior to traditional alginate. The outgassing effect was minimal for most materials tested. Alginate substitute materials are superior replacements for irreversible hydrocolloid." }, { "pmid": "22287575", "year": 2012, "title": "Oral intake of hydrogen-rich water inhibits intimal hyperplasia in arterialized vein grafts in rats.", "title_en": null, "title_de": "Die orale Aufnahme von wasserstoffreichem Wasser hemmt die Intimahyperplasie in arterialisierten Venentransplantaten bei Ratten.", "journal": "Cardiovascular research", "authors": "Sun et al.", "author_search": "sun sun", "doi": "10.1093/cvr/cvs024", "doi_url": "https://doi.org/10.1093/cvr/cvs024", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/22287575/", "url": "https://h2medicine.org/studies/study-sun-2012-oral-intake-inhibits-intimal/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise", "cardiovascular", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2012 · Sun et al. — Oral intake of hydrogen-rich water inhibits intimal hyperplasia in arterialized vein grafts in rats.", "summary": "Vein grafts used in bypass surgery frequently fail due to intimal hyperplasia — thickening of the vessel wall that narrows the lumen over time. This rat study found that drinking hydrogen-rich water (HRW) significantly suppressed intimal hyperplasia after vein grafting, improved endothelial integrity, reduced platelet and immune cell aggregation, and inhibited key inflammatory and remodeling proteins (MMP-2, MMP-9, p38 MAPK). These results are from a rat model — human clinical data do not exist for this specific application.", "assessment": "This is a preclinical animal study in rats — findings cannot be directly extrapolated to human patients. The mechanistic data are consistent and internally coherent, pointing to anti-inflammatory and antioxidant mechanisms via oxidative stress reduction. The study design is solid for a preclinical vascular study. However, vein graft intimal hyperplasia in humans involves additional complexity, and no clinical trials on this indication exist. The results are hypothesis-generating for potential future clinical investigation.", "abstract": "AIMS: Arterialized vein grafts often fail due to intimal hyperplasia. Hydrogen potently protects organs and cells from many insults via its anti-inflammatory and antioxidant properties. We investigated the efficacy of oral administration of hydrogen-rich water (HW) for prevention of intimal hyperplasia. METHODS AND RESULTS: The inferior vena cava was excised, stored in cold Ringer solution for 2 h, and placed as an interposition graft in the abdominal aorta of syngeneic Lewis rats. HW was generated by immersing a magnesium stick in tap water (Mg + 2H(2)O → Mg (OH)(2) + H(2)). Beginning on the day of graft implantation, recipients were given tap water [regular water (RW)], HW or HW that had been subsequently degassed water (DW). Six weeks after grafting, the grafts in the rats given RW or DW had developed intimal hyperplasia, accompanied by increased oxidative injury. HW significantly suppressed intimal hyperplasia. One week after grafting, the grafts in HW-treated rats exhibited improved endothelial integrity with less platelet and white blood cell aggregation. Up-regulation of the mRNAs for intracellular adhesion molecules was attenuated in the vein grafts of the rats receiving HW. Activation of p38 mitogen-activated protein kinase, matrix metalloproteinase (MMP)-2, and MMP-9 was also significantly inhibited in grafts receiving HW. In rat smooth muscle cell (A7r5) cultures, hydrogen treatment for 24 h reduced smooth muscle cell migration. CONCLUSION: Drinking HW significantly reduced neointima formation after vein grafting in rats. Drinking HW may have therapeutic value as a novel therapy for intimal hyperplasia and could easily be incorporated into daily life.", "conclusion": "Drinking HW significantly reduced neointima formation after vein grafting in rats. Drinking HW may have therapeutic value as a novel therapy for intimal hyperplasia and could easily be incorporated into daily life." }, { "pmid": "22259109", "year": 2012, "title": "Estimation of molecular hydrogen consumption in the human whole body after the ingestion of hydrogen-rich water.", "title_en": null, "title_de": "Schätzung des Verbrauchs von molekularem Wasserstoff im gesamten menschlichen Körper nach der Aufnahme von wasserstoffreichem Wasser", "journal": "Advances in experimental medicine and biology", "authors": "Shimouchi et al.", "author_search": "shimouchi shimouchi", "doi": "10.1007/978-1-4614-1566-4_36", "doi_url": "https://doi.org/10.1007/978-1-4614-1566-4_36", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/22259109/", "url": "https://h2medicine.org/studies/study-shimouchi-2012-estimation-consumption-whole-body/", "methods": [ "drinking-hrw" ], "indications": [ "other" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2012 · Shimouchi et al. — Estimation of Molecular Hydrogen Consumption in the Human Whole Body after Ingestion of Hydrogen-Rich Water", "summary": "How much H₂ does the human body actually absorb and consume after drinking hydrogen-rich water? This pharmacokinetic study measured H₂ in exhaled breath to estimate whole-body H₂ uptake and metabolism after oral ingestion. It provides fundamental dosimetry data for H₂ therapy research. (Advances in Experimental Medicine and Biology, 2012.)", "assessment": "This study addresses a genuinely important but often overlooked question in H₂ research: what fraction of ingested H₂ is actually absorbed and metabolized systemically? Breath-H₂ tracking is a validated indirect method for this purpose. Limitations: No abstract was available for this entry, which prevents assessment of sample size, exact methodology, or specific findings. The study appears to be methodological/pharmacokinetic rather than a clinical outcomes trial. Results should be interpreted as dose-estimation data, not evidence of therapeutic efficacy. The journal is a specialist conference proceedings volume, not a high-impact clinical journal.", "abstract": null, "conclusion": null }, { "pmid": "22070900", "year": 2012, "title": "Hydrogen-rich electrolyzed warm water represses wrinkle formation against UVA ray together with type-I collagen production and oxidative-stress diminishment in fibroblasts and cell-injury prevention in keratinocytes.", "title_en": null, "title_de": "Wasserstoffreiches elektrolysiertes warmes Wasser unterdrückt die Faltenbildung gegen UVA-Strahlen zusammen mit der Typ-I-Kollagenproduktion und der Verringerung von oxidativem Stress in Fibroblasten sowie der Verhinderung von Zellschäden in Keratinozyten.", "journal": "Journal of photochemistry and photobiology. B, Biology", "authors": "Kato et al.", "author_search": "kato kato", "doi": "10.1016/j.jphotobiol.2011.09.006", "doi_url": "https://doi.org/10.1016/j.jphotobiol.2011.09.006", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/22070900/", "url": "https://h2medicine.org/studies/study-kato-2012-electrolyzed-warm-represses-wrinkle/", "methods": [ "bath-topical" ], "indications": [ "cancer", "skin-aging", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2012 · Kato et al. — Hydrogen-rich electrolyzed warm water represses wrinkle formation against UVA ray together with type-I collagen production and oxidative-stress diminishment in fibroblasts and cell-injury prevention in keratinocytes.", "summary": "UVA radiation from sunlight damages skin cells, promotes wrinkle formation, and reduces collagen production — primarily via oxidative stress from reactive oxygen species. This study found that hydrogen-rich warm water (prepared at 41°C via electrolysis) significantly increased type-I collagen production in skin fibroblasts, reduced UVA-induced cell death and DNA damage in keratinocytes, and suppressed intracellular superoxide radical generation. A small pilot bathing trial in six Japanese subjects showed wrinkle improvement in four participants. This is a predominantly cell-culture study with a very small pilot human observation — not a clinical trial.", "assessment": "This is primarily a preclinical in-vitro study on skin cells, with a very small and uncontrolled human pilot observation (6 subjects, no control group). The cell culture data are mechanistically plausible and show meaningful collagen and protective effects. However, the human observation cannot be considered clinical evidence — the sample is far too small and lacks controls. Proper randomized clinical trials are needed. The data are interesting for basic science and provide a mechanistic rationale for H₂ in skin aging, but skin care claims require a much higher evidence standard.", "abstract": "Hydrogen-rich electrolyzed warm water (HW) was prepared at 41°C and exhibited dissolved hydrogen (DH) of 1.13 ppm and an oxidation-reduction potential (ORP) of -741 mV in contrast to below 0.01 ppm and+184 mV for regular warm water (RW). Fibroblasts OUMS-36 and keratinocytes HaCaT were used to examine effects of HW against UVA-ray irradiation. Type-I collagen was synthesized 1.85- to 2.03-fold more abundantly by HW application for 3-5 days than RW in OUMS-36 fibroblasts, and localized preferentially around the nuclei as shown by immunostain. HW application significantly prevented cell death and DNA damages such as nuclear condensation and fragmentation in UVA-irradiated HaCaT keratinocytes as estimated by WST-1 and Hoechst 33342 assays. HW significantly suppressed UVA-induced generation of intracellular superoxide anion radicals in both the cell lines according to NBT assay. Wrinkle repression was clinically assessed using a HW-bathing. Six Japanese subjects were enrolled in a trial of HW-bathing (DH, 0.2-0.4 ppm) every day for 3 months. HW-bathing significantly improved wrinkle in four subjects on the back of neck on 90th day as compared to 0 day. Thus, HW may serve as daily skin care to repress UVA-induced skin damages by ROS-scavenging and promotion of type-I collagen synthesis in dermis.", "conclusion": "HW-bathing significantly improved wrinkle in four subjects on the back of neck on 90th day as compared to 0 day. Thus, HW may serve as daily skin care to repress UVA-induced skin damages by ROS-scavenging and promotion of type-I collagen synthesis in dermis." }, { "pmid": "21736547", "year": 2011, "title": "Recent progress toward hydrogen medicine: potential of molecular hydrogen for preventive and therapeutic applications.", "title_en": null, "title_de": "Jüngste Fortschritte in Richtung Wasserstoffmedizin: Potenzial von molekularem Wasserstoff für präventive und therapeutische Anwendungen.", "journal": "Current pharmaceutical design", "authors": "Ohta", "author_search": "ohta ohta", "doi": "10.2174/138161211797052664", "doi_url": "https://doi.org/10.2174/138161211797052664", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/21736547/", "url": "https://h2medicine.org/studies/study-ohta-2011-recent-progress-toward-medicine/", "methods": [ "inhalation", "saline-iv", "bath-topical", "drinking-hrw" ], "indications": [ "cancer", "skin-aging", "eye", "immune-system", "allergy", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2011 · Ohta — Recent progress toward hydrogen medicine: potential of molecular hydrogen for preventive and therapeutic applications.", "summary": "Since the landmark 2007 Nature Medicine paper demonstrating that molecular hydrogen (H₂) selectively neutralizes toxic hydroxyl radicals, the field of hydrogen medicine has grown rapidly. This comprehensive review by Shigeo Ohta — one of the founding figures of H₂ research — summarizes evidence across more than 38 diseases and physiological states, covering multiple delivery methods (inhalation, drinking, bathing, injection, eye drops) and both oxidative stress and anti-inflammatory / anti-allergic mechanisms. It is a review, not a new clinical trial.", "assessment": "This is a narrative review by a leading figure in H₂ research, summarizing the state of the field in 2011. It provides a useful map of the breadth of H₂ biology at that time and articulates the safety and selectivity rationale clearly. As a review, it synthesizes existing evidence rather than producing new experimental proof. A key honest caveat: much of the evidence cited comes from preclinical (animal/cell) studies, and the clinical evidence base was still early. The mechanisms underlying H₂'s effects beyond •OH scavenging remained unexplained. The paper is historically important but should be read as a 2011 state-of-knowledge summary, not as a current systematic evidence review.", "abstract": "Persistent oxidative stress is one of the major causes of most lifestyle-related diseases, cancer and the aging process. Acute oxidative stress directly causes serious damage to tissues. Despite the clinical importance of oxidative damage, antioxidants have been of limited therapeutic success. We have proposed that molecular hydrogen (H(2)) has potential as a \"novel\" antioxidant in preventive and therapeutic applications [Ohsawa et al., Nat Med. 2007: 13; 688-94]. H(2) has a number of advantages as a potential antioxidant: H(2) rapidly diffuses into tissues and cells, and it is mild enough neither to disturb metabolic redox reactions nor to affect reactive oxygen species (ROS) that function in cell signaling, thereby, there should be little adverse effects of consuming H(2). There are several methods to ingest or consume H(2), including inhaling hydrogen gas, drinking H(2)-dissolved water (hydrogen water), taking a hydrogen bath, injecting H(2)- dissolved saline (hydrogen saline), dropping hydrogen saline onto the eye, and increasing the production of intestinal H(2) by bacteria. Since the publication of the first H(2) paper in Nature Medicine in 2007, the biological effects of H(2) have been confirmed by the publication of more than 38 diseases, physiological states and clinical tests in leading biological/medical journals, and several groups have started clinical examinations. Moreover, H(2) shows not only effects against oxidative stress, but also various anti-inflammatory and antiallergic effects. H(2) regulates various gene expressions and protein-phosphorylations, though the molecular mechanisms underlying the marked effects of very small amounts of H(2) remain elusive.", "conclusion": "Moreover, H(2) shows not only effects against oxidative stress, but also various anti-inflammatory and antiallergic effects. H(2) regulates various gene expressions and protein-phosphorylations, though the molecular mechanisms underlying the marked effects of very small amounts of H(2) remain elusive." }, { "pmid": "21736540", "year": 2011, "title": "The principle and the potential approach to ROS-dependent cytotoxicity by non-pharmaceutical therapies: optimal use of medical gases with antioxidant properties.", "title_en": null, "title_de": "Das Prinzip und der mögliche Ansatz zur ROS-abhängigen Zytotoxizität durch nichtpharmazeutische Therapien: optimale Nutzung medizinischer Gase mit antioxidativen Eigenschaften.", "journal": "Current pharmaceutical design", "authors": "Noda et al.", "author_search": "noda noda", "doi": "10.2174/138161211797052600", "doi_url": "https://doi.org/10.2174/138161211797052600", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/21736540/", "url": "https://h2medicine.org/studies/study-noda-2011-principle-approach-ros-dependent/", "methods": [ "unspecified" ], "indications": [ "diabetes", "neurology", "cancer", "eye", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2011 · Noda et al. — The principle and the potential approach to ROS-dependent cytotoxicity by non-pharmaceutical therapies: optimal use of medical gases with antioxidant properties.", "summary": "Oxidative stress and reactive oxygen species (ROS) are implicated in many major diseases including inflammation, diabetes, glaucoma, cancer, ischemia, and neurodegeneration. This review examines how medical gases — carbon monoxide (CO), hydrogen sulfide (H₂S), and molecular hydrogen (H₂) — can act as antioxidants by directly scavenging or neutralizing harmful ROS. It also discusses how cells can produce their own ROS-resistant proteins as a complementary defense. This is a review article; no new experiments are reported.", "assessment": "This is a narrative review covering the mechanistic rationale for medical gas therapies (CO, H₂S, and H₂) in ROS-related diseases. It provides a useful conceptual framework for understanding H₂ as an antioxidant therapeutic but does not generate new experimental evidence and should not be read as clinical proof of efficacy for any specific condition. The evidence base at the time of publication was predominantly preclinical. The comparative discussion of CO, H₂S, and H₂ is a useful distinguishing context.", "abstract": "Regulation of cellular redox balances is important for the homeostasis of human health. Thus, many important human diseases, such as inflammation, diabetes, glaucoma, cancers, ischemia and neurodegenerative diseases, have been investigated in the field of reactive oxygen species (ROS) and oxidative stress. To overcome the harmful effect of oxidative stress and ROS, one can directly eliminate them by medical gases such as carbon monoxide (CO), hydrogen sulphide (H(2)S), and molecular hydrogen (H(2)), or one can induce ROS-resistant proteins and antioxidant enzymes to antagonize oxidative stresses. This article reviews the molecular mechanisms how these medical gasses work as antioxidants, and how ROS resistant proteins are produced in the physiological context. Targeted therapeutic modalities to scavenge or prevent ROS might be applied in the prevention and treatment of ROS-related diseases in the near future.", "conclusion": "This article reviews the molecular mechanisms how these medical gasses work as antioxidants, and how ROS resistant proteins are produced in the physiological context. Targeted therapeutic modalities to scavenge or prevent ROS might be applied in the prevention and treatment of ROS-related diseases in the near future." }, { "pmid": "21573992", "year": 2011, "title": "Defective protein folding and aggregation as the basis of neurodegenerative diseases: the darker aspect of proteins.", "title_en": null, "title_de": "Fehlerhafte Proteinfaltung und Aggregation als Grundlage neurodegenerativer Erkrankungen: der dunklere Aspekt von Proteinen.", "journal": "Cell biochemistry and biophysics", "authors": "Naeem et al.", "author_search": "naeem naeem", "doi": "10.1007/s12013-011-9200-x", "doi_url": "https://doi.org/10.1007/s12013-011-9200-x", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/21573992/", "url": "https://h2medicine.org/studies/study-naeem-2011-defective-protein-folding-aggregation/", "methods": [ "unspecified" ], "indications": [ "neurology", "cancer" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2011 · Naeem et al. — Defective protein folding and aggregation as the basis of neurodegenerative diseases: the darker aspect of proteins.", "summary": "When proteins fail to fold correctly, they can form toxic aggregates — a process central to Alzheimer's, Parkinson's, Huntington's, ALS, and other neurodegenerative diseases. This review examines the molecular mechanisms of protein misfolding and aggregation, the role of molecular chaperones in quality control, and the consequences when this system fails. The connection to „hydrogen\" in this paper is indirect: intermolecular hydrogen bonding between misfolded protein molecules drives the aggregation process. This is not a study of molecular H₂ as a therapeutic gas.", "assessment": "This paper is not relevant to molecular hydrogen (H₂) therapy or biology. It reviews the mechanisms of protein misfolding and aggregation in neurodegenerative diseases. The term „hydrogen\" refers to intermolecular hydrogen bonds in protein aggregates — a standard biochemical concept with no connection to dissolved H₂ gas. No conclusions about H₂ health effects can be drawn from this study. It appears in H₂ research databases as an indexing artifact.", "abstract": "The ability of a polypeptide to fold into a unique, functional, and three-dimensional structure depends on the intrinsic properties of the amino acid sequence, function of the molecular chaperones, proteins, and enzymes. Every polypeptide has a finite tendency to misfold and this forms the darker side of the protein world. Partially folded and misfolded proteins that escape the cellular quality control mechanism have the high tendency to form inter-molecular hydrogen bonding between the same protein molecules resulting in aggregation. This review summarizes the underlying and universal mechanism of protein folding. It also deals with the factors responsible for protein misfolding and aggregation. This article describes some of the consequences of such behavior particularly in the context of neurodegenerative conformational diseases such as Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis and other non-neurodegenerative conformational diseases such as cancer and cystic fibrosis etc. This will encourage a more proactive approach to the early diagnosis of conformational diseases and nutritional counseling for patients.", "conclusion": "This article describes some of the consequences of such behavior particularly in the context of neurodegenerative conformational diseases such as Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis and other non-neurodegenerative conformational diseases such as cancer and cystic fibrosis etc. This will encourage a more proactive approach to the early diagnosis of conformational d" }, { "pmid": "21562446", "year": 2011, "title": "Feasibility of measuring human pancreatic perfusion in vivo using imaging techniques.", "title_en": null, "title_de": "Machbarkeit der Messung der menschlichen Pankreasperfusion in vivo mittels bildgebender Verfahren", "journal": "Pancreas", "authors": "Tsushima et al.", "author_search": "tsushima tsushima", "doi": "10.1097/mpa.0b013e318215ac22", "doi_url": "https://doi.org/10.1097/mpa.0b013e318215ac22", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/21562446/", "url": "https://h2medicine.org/studies/study-tsushima-2011-feasibility-measuring-pancreatic-perfusion/", "methods": [], "indications": [ "skin-aging" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "tracer-clearance", "headline": "2011 · Tsushima et al. — Feasibility of Measuring Human Pancreatic Perfusion In Vivo Using Imaging Techniques", "summary": "This study evaluates methods for measuring pancreatic blood flow using CT and other imaging modalities — not H₂ therapy. Hydrogen gas appears only as a reference measurement technique (the „hydrogen clearance method“) used historically for organ perfusion measurement. This paper is a methodology comparison for pancreatic imaging and has no clinical H₂ therapeutic intervention. (Pancreas, 2011.)", "assessment": "Off-topic for H₂ therapy. This paper uses hydrogen gas exclusively as a perfusion measurement tracer (the H₂-clearance technique), which is a diagnostic tool unrelated to hydrogen therapy. The study does not investigate H₂ as a therapeutic intervention. It should not be interpreted as evidence for H₂ therapeutic effects on the pancreas or any other organ. Its inclusion in an H₂ therapy database appears to be a metadata error — likely triggered by the word „hydrogen“ in the methods section.", "abstract": "OBJECTIVE: The objective of this study was to demonstrate the feasibility of pancreatic perfusion computed tomography (CT) and review pancreatic perfusion measurements by various imaging modalities. METHODS: Dynamic CT data from 8 patients (4 men; mean age, 64.8 [SD, 12.1] years; range, 40-80 years) with normal pancreas were analyzed using 2 analytical models: the maximum-slope and compartment-model methods. Literature search was also performed. RESULTS: Although the perfusion value estimated by the maximum-slope method (88.1 [SD, 42.1] mL/min per 100 mL) was significantly smaller than that of the compartment-model method (127.0 [SD, 70.5]; P < 0.001), there was a linear correlation between them (r = 0.97, P < 0.001). In the literature review, 15 studies that reported the absolute values of normal pancreatic perfusion, by using perfusion CT, dynamic magnetic resonance imaging, hydrogen gas clearance method, and 15O-H2O-positron emission tomography were found. The reported mean values of normal pancreatic perfusion ranged from 38.4 to 356 mL/min per 100 mL, and there was a great deal of individual variation. CONCLUSIONS: Perfusion CT may provide reliable perfusion measurements of the pancreas, and the normal value was estimated at around 100 mL/min per 100 mL with a great deal of individual variation. The maximum-slope method may provide a lower perfusion value compared with the compartment-model method.", "conclusion": "Perfusion CT may provide reliable perfusion measurements of the pancreas, and the normal value was estimated at around 100 mL/min per 100 mL with a great deal of individual variation. The maximum-slope method may provide a lower perfusion value compared with the compartment-model method." }, { "pmid": "21251046", "year": 2011, "title": "Hydrogen resuscitation, a new cytoprotective approach.", "title_en": null, "title_de": "Wasserstoff-Reanimation, ein neuer zytoprotektiver Ansatz.", "journal": "Clinical and experimental pharmacology & physiology", "authors": "Zheng et al.", "author_search": "zheng zheng", "doi": "10.1111/j.1440-1681.2011.05479.x", "doi_url": "https://doi.org/10.1111/j.1440-1681.2011.05479.x", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/21251046/", "url": "https://h2medicine.org/studies/study-zheng-2011-resuscitation-cytoprotective-approach/", "methods": [ "inhalation" ], "indications": [ "liver", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2011 · Zheng et al. — Hydrogen resuscitation, a new cytoprotective approach.", "summary": "Oxidative injury — from ischemia-reperfusion, inflammation, trauma, or toxins — damages cells, tissues, and organs by unleashing reactive oxygen species. This review introduces the concept of „hydrogen resuscitation”: using molecular hydrogen (H₂) as a cytoprotective intervention to protect cells from oxidative damage and help restore function. The review covers three delivery routes (inhalation, hydrogen-enriched fluid, endogenous bacterial production) and surveys preclinical evidence across multiple injury models. As a review, it synthesizes existing literature rather than reporting new experiments.", "assessment": "This is a narrative review synthesizing preclinical evidence for H₂ as a cytoprotective agent across multiple oxidative injury models. It is well-structured and honest about limitations: the mechanistic picture was incomplete in 2011, and clinical validation had not been established. The evidence presented is predominantly preclinical (animal and cell studies); clinical data are not the focus. The review is useful as a conceptual framework for H₂ resuscitation research and for understanding the state of the field in 2011. Readers should note that substantial further clinical research has occurred since this review was published.", "abstract": "1. Hydrogen is a colourless, odourless, tasteless and flammable gas. Hydrogen is considered a physiologically inert gas and is often used in deep sea diving medicine. In mammals, endogenous hydrogen is produced as a result of the fermentation of non-digestible carbohydrates by intestinal bacteria and it is absorbed into the systemic circulation. 2. Recent evidence indicates that hydrogen is a potent anti-oxidative, anti-apoptotic and anti-inflammatory agent and so may have potential medical application. The present review evaluates the concept of 'hydrogen resuscitation', based on knowledge that hydrogen treatment effectively protects cells, tissues and organs against oxidative injury and helps them recover from dysfunction. 3. Hydrogen therapy can be delivered by inhalation, the administration of hydrogen-enriched fluid or by approaches that affect endogenous hydrogen production. 4. Studies have shown that hydrogen resuscitation has cytoprotective effects in different cell types and disease models, including ischaemia-reperfusion injury, inflammation, toxicity, trauma and metabolic disease. The underlying mechanism may be the selective elimination of hydroxyl radicals, although other mechanisms may also be involved (e.g. hydrogen functioning as a gaseous signalling molecule). 5. Hydrogen resuscitation may have several potential advantages over current pharmacological therapies for oxidative injuries. However, more work is needed to identify the precise mechanism underlying the actions of hydrogen and to validate its therapeutic potential in the clinical setting.", "conclusion": "Hydrogen resuscitation may have several potential advantages over current pharmacological therapies for oxidative injuries. However, more work is needed to identify the precise mechanism underlying the actions of hydrogen and to validate its therapeutic potential in the clinical setting." }, { "pmid": "21244359", "year": 2011, "title": "Melatonin-mitochondria interplay in health and disease.", "title_en": null, "title_de": "Melatonin-Mitochondrien-Wechselspiel in Gesundheit und Krankheit", "journal": "Current topics in medicinal chemistry", "authors": "Acuña Castroviejo et al.", "author_search": "acuña castroviejo acuña castroviejo", "doi": "10.2174/156802611794863517", "doi_url": "https://doi.org/10.2174/156802611794863517", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/21244359/", "url": "https://h2medicine.org/studies/study-acunacastroviejo-2011-melatonin-mitochondria-interplay-health/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise", "neurology", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2011 · Acuña Castroviejo — Melatonin-Mitochondria Interplay in Health and Disease", "summary": "This review examines how melatonin interacts with mitochondria to counteract oxidative and nitrosative stress — one of the core mechanisms underlying a wide range of diseases. The „hydrogen hypothesis“ of mitochondrial origin is discussed as part of the evolutionary background. The review synthesises experimental and clinical evidence for melatonin's protective role in mitochondrial dysfunction. (Current Topics in Medicinal Chemistry, 2011.)", "assessment": "This is a narrative review, not a clinical trial or controlled experiment. It synthesises existing data on melatonin and mitochondria. The conclusions about melatonin's benefits rest on a broad base of experimental (mostly animal and cell culture) and some clinical evidence. Importantly: the „hydrogen hypothesis“ mentioned in this paper is an evolutionary theory about mitochondrial origins — it has no direct bearing on molecular hydrogen therapy. Readers should not confuse these two distinct uses of the word „hydrogen“. The review provides useful mechanistic background but does not establish clinical efficacy for any specific therapy in humans by itself.", "abstract": "Although two main hypotheses of mitochondrial origin have been proposed, i.e., the autogenous and the endosymbiotic, only the second is being seriously considered currently. The 'hydrogen hypothesis' invokes metabolic symbiosis as the driving force for a symbiotic association between an anaerobic, strictly hydrogen-dependent (the host) and an eubacterium (the symbiont) that was able to respire, but which generated molecular hydrogen as an end product of anaerobic metabolism. The resulting proto-eukaryotic cell would have acquired the essentials of eukaryotic energy metabolism, evolving not only aerobic respiration, but also the physiological cost of the oxygen consumption, i.e., generation of reactive oxygen species (ROS) and the associated oxidative damage. This is not the only price to pay for respiring oxygen: mitochondria possess nitric oxide (NO·) for regulatory purposes but, in some instances it may react with superoxide anion radical to produce the toxic reactive nitrogen species (RNS), i.e. peroxynitrite anion, and the subsequent nitrosative damage. New mitochondria contain their own genome with a modified genetic code that is highly conserved among mammals. The transcription of certain mitochondrial genes may depend on the redox potential of the mitochondrial membrane. Mitochondria are related to the life and death of cells. They are involved in energy production and conservation, having an uncoupling mechanism to produce heat instead of ATP, but they are also involved in programmed cell death. Increasing evidence suggest the participation of mitochondria in neurodegenerative and neuromuscular diseases involving alterations in both nuclear (nDNA) and mitochondrial (mtDNA) DNA. Melatonin is a known powerful antioxidant and anti-inflammatory and increasing experimental and clinical evidence shows its beneficial effects against oxidative/nitrosative stress status, including that involving mitochondrial dysfunction. This review summarizes the data and mechanisms of action of melatonin in relation to mitochondrial pathologies.", "conclusion": "Melatonin is a known powerful antioxidant and anti-inflammatory and increasing experimental and clinical evidence shows its beneficial effects against oxidative/nitrosative stress status, including that involving mitochondrial dysfunction. This review summarizes the data and mechanisms of action of melatonin in relation to mitochondrial pathologies." }, { "pmid": "22417501", "year": 2011, "title": "Digestibility, fermentability, and energy value of highly cross-linked phosphate tapioca starch in men.", "title_en": null, "title_de": "Verdaulichkeit, Fermentierbarkeit und Energiewert von hochgradig quervernetzter Phosphat-Tapiokastärke bei Männern", "journal": "Journal of food science", "authors": "Tachibe et al.", "author_search": "tachibe tachibe", "doi": "10.1111/j.1750-3841.2011.02247.x", "doi_url": "https://doi.org/10.1111/j.1750-3841.2011.02247.x", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/22417501/", "url": "https://h2medicine.org/studies/study-tachibe-2011-digestibility-fermentability-energy-value/", "methods": [], "indications": [ "diabetes" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "breath-test", "headline": "2011 · Tachibe et al. — Digestibility, Fermentability, and Energy Value of Highly Cross-Linked Phosphate Tapioca Starch in Men", "summary": "This study measures breath hydrogen to assess gut fermentation of a modified tapioca starch — it is a food science/nutrition study, not an H₂ therapy trial. Exhaled H₂ is used here as an indirect marker of colonic bacterial fermentation, a standard clinical nutrition method. No molecular hydrogen is administered therapeutically. (Journal of Food Science, 2011.)", "assessment": "Off-topic for H₂ therapy. Breath hydrogen in this study is a fermentation marker, not a therapeutic agent or intervention. The study investigates modified food starch, not hydrogen medicine. No H₂ therapeutic intervention of any kind was applied. This paper appears to have been included in an H₂ database due to the keyword „breath hydrogen“ in the methods, which is a measurement tool here, not a treatment.", "abstract": "The objective of this study was to determine glycemic and breath hydrogen responses in 10 healthy men in response to highly cross-linked starch phosphate (HXLS), made of tapioca starch (TS). Plasma glucose concentration was analyzed at baseline and at 30, 60, 90, 120, 150, and 180 min postprandially. In addition, breath hydrogen excretion was measured at baseline and at hourly intervals, over 10 h, after test substance challenge. When compared with unmodified TS easily digested, the area under the curve of plasma glucose of HXLS was 64% smaller, and was almost the same as that of microcrystalline cellulose. When compared with fructo-oligosaccharide rapidly fermented by the microbial bacteria, the area under the excretion curve of breath hydrogen gas of HXLS was 93% smaller, and was almost the same as that of water only. These results show that HXLS is harder to digest and ferment than unmodified TS in men.", "conclusion": "When compared with fructo-oligosaccharide rapidly fermented by the microbial bacteria, the area under the excretion curve of breath hydrogen gas of HXLS was 93% smaller, and was almost the same as that of water only. These results show that HXLS is harder to digest and ferment than unmodified TS in men." }, { "pmid": "22079833", "year": 2011, "title": "The Trichomonas vaginalis hydrogenosome proteome is highly reduced relative to mitochondria, yet complex compared with mitosomes.", "title_en": null, "title_de": "Das Hydrogenosom-Proteom von Trichomonas vaginalis ist im Vergleich zu Mitochondrien stark reduziert, jedoch komplex im Vergleich zu Mitosomen", "journal": "International journal for parasitology", "authors": "Schneider et al.", "author_search": "schneider schneider", "doi": "10.1016/j.ijpara.2011.10.001", "doi_url": "https://doi.org/10.1016/j.ijpara.2011.10.001", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/22079833/", "url": "https://h2medicine.org/studies/study-schneider-2011-trichomonas-vaginalis-hydrogenosome-proteome/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2011 · Schneider — The Trichomonas vaginalis Hydrogenosome Proteome Is Highly Reduced Relative to Mitochondria, Yet Complex Compared with Mitosomes", "summary": "This cell-biology study maps the full protein inventory of the hydrogenosome — a molecular-hydrogen-producing organelle in the human parasite Trichomonas vaginalis — revealing 569 proteins, far fewer than mitochondria but far more than the most stripped-down mitochondria-related organelles. The work illuminates how evolution has shaped hydrogen-producing cellular machinery. This is basic microbiology research with no direct application to H₂ therapy. (International Journal for Parasitology, 2011.)", "assessment": "This is an in-vitro / cell-biology study — specifically a proteomics analysis of a parasite organelle. It has no direct relevance to molecular hydrogen therapy in humans. Its connection to „hydrogen“ is purely biochemical: hydrogenosomes are named for producing H₂ as a metabolic byproduct. Honest note: this study is not evidence for or against any health benefit of drinking hydrogen-rich water or inhaling H₂ gas. It is valuable evolutionary and microbiological science, but should not be cited in a therapeutic context without clear clarification of its scope.", "abstract": "The human pathogen Trichomonas vaginalis lacks conventional mitochondria and instead contains divergent mitochondrial-related organelles. These double-membrane bound organelles, called hydrogenosomes, produce molecular hydrogen. Phylogenetic and biochemical analyses of hydrogenosomes indicate a common origin with mitochondria; however identification of hydrogenosomal proteins and studies on its metabolism have been limited. Here we provide a detailed proteomic analysis of the T. vaginalis hydrogenosome. The proteome of purified hydrogenosomes consists of 569 proteins, a number substantially lower than the 1,000-1,500 proteins reported for fungal and animal mitochondrial proteomes, yet considerably higher than proteins assigned to mitosomes. Pathways common to and distinct from both mitochondria and mitosomes were revealed by the hydrogenosome proteome. Proteins known to function in amino acid and energy metabolism, Fe-S cluster assembly, flavin-mediated catalysis, oxygen stress response, membrane translocation, chaperonin functions, proteolytic processing and ATP hydrolysis account for ∼30% of the hydrogenosome proteome. Of the 569 proteins in the hydrogenosome proteome, many appear to be associated with the external surface of hydrogenosomes, including large numbers of GTPases and ribosomal proteins. Glycolytic proteins were also found to be associated with the hydrogenosome proteome, similar to that previously observed for mitochondrial proteomes. Approximately 18% of the hydrogenosomal proteome is composed of hypothetical proteins of unknown function, predictive of multiple activities and properties yet to be uncovered for these highly adapted organelles.", "conclusion": "Glycolytic proteins were also found to be associated with the hydrogenosome proteome, similar to that previously observed for mitochondrial proteomes. Approximately 18% of the hydrogenosomal proteome is composed of hypothetical proteins of unknown function, predictive of multiple activities and properties yet to be uncovered for these highly adapted organelles." }, { "pmid": "21859325", "year": 2011, "title": "Variation in lunar neutron dose estimates.", "title_en": null, "title_de": "Variation in den Schätzungen der lunaren Neutronendosis", "journal": "Radiation research", "authors": "Slaba et al.", "author_search": "slaba slaba", "doi": "10.1667/rr2616.1", "doi_url": "https://doi.org/10.1667/rr2616.1", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/21859325/", "url": "https://h2medicine.org/studies/study-slaba-2011-variation-lunar-neutron-dose/", "methods": [ "unspecified" ], "indications": [ "cancer" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2011 · Slaba — Variation in Lunar Neutron Dose Estimates", "summary": "This theoretical physics study calculates how much albedo neutrons — reflected cosmic rays — contribute to radiation exposure on the lunar surface, and shows that hydrogen-rich shielding materials such as polyethylene can reduce that exposure. The study is pure radiation physics modelling; it has no connection to molecular hydrogen therapy in humans. (Physics in Medicine and Biology, 2011.)", "assessment": "This is a theoretical/computational study in space radiation physics. It is not a study of molecular hydrogen therapy or of any biological effect of H₂. Its relevance to this database is marginal: the mention of „hydrogen“ refers exclusively to hydrogen atoms as a component of shielding materials. Honest note: this paper should not be cited in support of H₂ health claims. It belongs to aerospace medicine and radiation protection physics, not H₂ biomedicine.", "abstract": "The radiation environment on the Moon includes albedo neutrons produced by primary particles interacting with the lunar surface. In this work, HZETRN2010 is used to calculate the albedo neutron contribution to effective dose as a function of shielding thickness for four different space radiation environments and to determine to what extent various factors affect such estimates. First, albedo neutron spectra computed with HZETRN2010 are compared to Monte Carlo results in various radiation environments. Next, the impact of lunar regolith composition on the albedo neutron spectrum is examined, and the variation on effective dose caused by neutron fluence-to-effective dose conversion coefficients is studied. A methodology for computing effective dose in detailed human phantoms using HZETRN2010 is also discussed and compared. Finally, the combined variation caused by environmental models, shielding materials, shielding thickness, regolith composition and conversion coefficients on the albedo neutron contribution to effective dose is determined. It is shown that a single percentage number for characterizing the albedo neutron contribution to effective dose can be misleading. In general, the albedo neutron contribution to effective dose is found to vary between 1-32%, with the environmental model, shielding material and shielding thickness being the driving factors that determine the exact contribution. It is also shown that polyethylene or other hydrogen-rich materials may be used to mitigate the albedo neutron exposure.", "conclusion": "In general, the albedo neutron contribution to effective dose is found to vary between 1-32%, with the environmental model, shielding material and shielding thickness being the driving factors that determine the exact contribution. It is also shown that polyethylene or other hydrogen-rich materials may be used to mitigate the albedo neutron exposure." }, { "pmid": "21764987", "year": 2011, "title": "Hydrogen therapy attenuates irradiation-induced lung damage by reducing oxidative stress.", "title_en": null, "title_de": "Die Wasserstofftherapie mildert strahlungsinduzierte Lungenschäden durch Reduktion von oxidativem Stress", "journal": "American journal of physiology. Lung cellular and molecular physiology", "authors": "Terasaki et al.", "author_search": "terasaki terasaki", "doi": "10.1152/ajplung.00008.2011", "doi_url": "https://doi.org/10.1152/ajplung.00008.2011", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/21764987/", "url": "https://h2medicine.org/studies/study-terasaki-2011-attenuates-irradiation-induced-lung/", "methods": [ "inhalation" ], "indications": [ "cancer", "respiratory", "skin-aging", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2011 · Terasaki — Hydrogen Therapy Attenuates Irradiation-Induced Lung Damage by Reducing Oxidative Stress", "summary": "In irradiated human lung cells and in mice given whole-thorax irradiation, molecular hydrogen (H₂) — delivered as H₂-rich PBS, H₂-enriched drinking water, or 3% H₂ inhalation — significantly reduced oxidative stress markers, apoptosis, and lung fibrosis. These are encouraging preclinical results for a potential radioprotective strategy, but the findings come from cell culture and animal experiments and cannot yet be directly applied to human cancer patients. (American Journal of Physiology: Lung Cellular and Molecular Physiology, 2011.)", "assessment": "This is a well-designed animal and cell culture (preclinical) study. Both in-vitro (A549 cells) and in-vivo (mouse) components support the hypothesis that H₂ mitigates radiation-induced lung injury. The multi-modal outcome assessment (ESR, fluorescence, IHC, CT, fibrosis scoring) adds credibility. Limitations: mouse models of thoracic irradiation do not perfectly replicate human clinical scenarios; A549 is a cancer cell line, not normal lung epithelium. No human trials have yet confirmed these results in radiotherapy patients. The „no known toxicity“ claim refers only to the doses tested in this study. These findings are promising but remain preclinical evidence only.", "abstract": "Molecular hydrogen (H(2)) is an efficient antioxidant that diffuses rapidly across cell membranes, reduces reactive oxygen species (ROS), such as hydroxyl radicals and peroxynitrite, and suppresses oxidative stress-induced injury in several organs. ROS have been implicated in radiation-induced damage to lungs. Because prompt elimination of irradiation-induced ROS should protect lung tissue from damaging effects of irradiation, we investigated the possibility that H(2) could serve as a radioprotector in the lung. Cells of the human lung epithelial cell line A549 received 10 Gy irradiation with or without H(2) treatment via H(2)-rich PBS or medium. We studied the possible radioprotective effects of H(2) by analyzing ROS and cell damage. Also, C57BL/6J female mice received 15 Gy irradiation to the thorax. Treatment groups inhaled 3% H(2) gas and drank H(2)-enriched water. We evaluated acute and late-irradiation lung damage after H(2) treatment. H(2) reduced the amount of irradiation-induced ROS in A549 cells, as shown by electron spin resonance and fluorescent indicator signals. H(2) also reduced cell damage, measured as levels of oxidative stress and apoptotic markers, and improved cell viability. Within 1 wk after whole thorax irradiation, immunohistochemistry and immunoblotting showed that H(2) treatment reduced oxidative stress and apoptosis, measures of acute damage, in the lungs of mice. At 5 mo after irradiation, chest computed tomography, Ashcroft scores, and type III collagen deposition demonstrated that H(2) treatment reduced lung fibrosis (late damage). This study thus demonstrated that H(2) treatment is valuable for protection against irradiation lung damage with no known toxicity.", "conclusion": "At 5 mo after irradiation, chest computed tomography, Ashcroft scores, and type III collagen deposition demonstrated that H(2) treatment reduced lung fibrosis (late damage). This study thus demonstrated that H(2) treatment is valuable for protection against irradiation lung damage with no known toxicity." }, { "pmid": "21656033", "year": 2011, "title": "Fabrication and characterization of bioactive composite coatings on Mg-Zn-Ca alloy by MAO/sol-gel.", "title_en": null, "title_de": "Herstellung und Charakterisierung bioaktiver Verbundbeschichtungen auf einer Mg-Zn-Ca-Legierung durch MAO/Sol-Gel", "journal": "Journal of materials science. Materials in medicine", "authors": "Gao et al.", "author_search": "gao gao", "doi": "10.1007/s10856-011-4349-9", "doi_url": "https://doi.org/10.1007/s10856-011-4349-9", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/21656033/", "url": "https://h2medicine.org/studies/study-gao-2011-fabrication-characterization-bioactive-composite/", "methods": [ "inhalation", "bath-topical" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2011 · Gao — Fabrication and Characterization of Bioactive Composite Coatings on Mg-Zn-Ca Alloy by MAO/Sol-Gel", "summary": "This in-vitro materials science study develops a two-layer protective coating for magnesium alloy implants that dramatically reduces corrosion and supports cell adhesion — addressing one of the main obstacles to using biodegradable magnesium in medical implants, namely the rapid release of hydrogen gas during degradation. This is biomaterials engineering research, not a study of molecular hydrogen therapy. (Journal of Materials Science: Materials in Medicine, 2011.)", "assessment": "This is an in-vitro biomaterials study. It does not investigate any therapeutic effect of molecular hydrogen. Hydrogen appears here as an unwanted corrosion byproduct that the coating aims to suppress. Honest note: this paper is not evidence for H₂ therapy and should not be cited in that context. It is valid engineering research on biodegradable implant coatings. Results are from laboratory corrosion tests and cell culture; clinical performance in living tissue would require animal and human studies.", "abstract": "High corrosion rate and accumulation of hydrogen gas upon degradation impede magnesium alloys' clinical application as implants. In this work, micro-arc oxidation (MAO) was used to fabricate a porous coating on magnesium alloys as an intermediate layer to enhance the bonding strength of propolis layer. Then the composite coatings were fabricated using sol-gel method by dipping sample into the solution containing propolis and polylactic acid at 40 °C. The corrosion resistance of the samples was determined based on potentiodynamic polarization experiments and immersion tests. Biocompatibility was designed by observing the attachment and growth of wharton's jelly-derived mesenchymal stem cells (WJCs) on substrates with MAO coating and substrates with composite coatings. The results showed that, compared with that of Mg-Zn-Ca alloy, the corrosion current density of the samples with composite coatings decreased from 5.37 × 10⁻⁵ to 1.10 × 10⁻⁶ A/cm² and the corrosion potential increased by 240 mV. Composite coatings exhibit homogeneous corrosion behavior and can promote WJCs cell adhesion and proliferation. In the meantime, pH value was relatively stable during the immersion tests, which may be significant for cellular survival. In conclusion, our results indicate that composite coatings on Mg-Zn-Ca alloy fabricated by MAO/sol-gel method provide a new type bioactive material.", "conclusion": "In the meantime, pH value was relatively stable during the immersion tests, which may be significant for cellular survival. In conclusion, our results indicate that composite coatings on Mg-Zn-Ca alloy fabricated by MAO/sol-gel method provide a new type bioactive material." }, { "pmid": "21596020", "year": 2011, "title": "Hydrogen-rich medium protects human skin fibroblasts from high glucose or mannitol induced oxidative damage.", "title_en": null, "title_de": "Wasserstoffreiches Medium schützt menschliche Hautfibroblasten vor durch hohe Glukose oder Mannitol induzierten oxidativen Schäden", "journal": "Biochemical and biophysical research communications", "authors": "Yu et al.", "author_search": "yu yu", "doi": "10.1016/j.bbrc.2011.05.024", "doi_url": "https://doi.org/10.1016/j.bbrc.2011.05.024", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/21596020/", "url": "https://h2medicine.org/studies/study-yu-2011-medium-protects-skin-fibroblasts/", "methods": [ "unspecified" ], "indications": [ "diabetes", "skin-aging", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2011 · Yu — Hydrogen-Rich Medium Protects Human Skin Fibroblasts from High Glucose or Mannitol Induced Oxidative Damage", "summary": "In human skin fibroblasts stressed with high glucose or mannitol — models of diabetic oxidative stress — a hydrogen-rich culture medium significantly reduced intracellular superoxide, stabilised mitochondrial membrane potential, and lowered markers of DNA and protein oxidation damage. These are promising cell-culture results suggesting H₂ may protect skin cells under diabetic conditions, but this is in-vitro research that cannot directly confirm benefits in living human patients. (Biochemical and Biophysical Research Communications, 2011.)", "assessment": "This is an in-vitro cell culture study using primary human cells, which gives it somewhat more translational relevance than animal studies — but it is still not clinical evidence. The multi-marker oxidative stress assessment is methodologically solid. Limitations: cell culture conditions do not replicate the complex wound environment in diabetic skin; dose-response data for H₂ are not reported; no animal or human wound-healing outcomes are shown. The authors' suggestion of potential applications in diabetic skin disease is a hypothesis, not a demonstrated outcome. These results are scientifically interesting preclinical findings only.", "abstract": "Reactive oxygen species (ROS) are an important factor in the development of skin lesions in diabetes. A new antioxidant, hydrogen, can selectively neutralize hydroxyl radicals (()OH) and peroxynitrite (ONOO(-)) in cell-free systems, whereas it seldom reacts with other ROS. Fibroblasts are a key component of skin. In the present study, we investigated the protective effects of hydrogen-rich medium on human skin fibroblasts (HSFs) under oxidative stress. Confocal microscopy was used to assay both the intracellular superoxide anion (O(2)(-)) concentration and the mitochondrial membrane potential (ΔΨ). Cell viability was determined using the Cell Counting Kit-8 (CCK-8). The concentrations of cellular malonaldehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 3-nitrotyrosine (3-NT) were also measured. The results revealed that both mannitol and high glucose could cause oxidative stress in HSFs. Interestingly, the use of a hydrogen-rich medium significantly reduced the level of intracellular O(2)(-), stabilized the ΔΨ and attenuated production of MDA, 8-OHdG and 3-NT which efficiently enhanced the antioxidative defense system and protected the HSFs from subsequent oxidative stress damage. In other words, hydrogen decreased the excessive generation of intracellular O(2)(-) and elevated the cellular antioxidative defense. Based on our results, hydrogen may have applications in the treatment of skin diseases caused by diabetes.", "conclusion": "In other words, hydrogen decreased the excessive generation of intracellular O(2)(-) and elevated the cellular antioxidative defense. Based on our results, hydrogen may have applications in the treatment of skin diseases caused by diabetes." }, { "pmid": "21455114", "year": 2011, "title": "A possible prevention strategy of radiation pneumonitis: combine radiotherapy with aerosol inhalation of hydrogen-rich solution.", "title_en": null, "title_de": "Eine mögliche Präventionsstrategie für Strahlenpneumonitis: Kombination von Strahlentherapie mit Aerosol-Inhalation einer wasserstoffreichen Lösung", "journal": "Medical science monitor : international medical journal of experimental and clinical research", "authors": "Chuai et al.", "author_search": "chuai chuai", "doi": "10.12659/msm.881698", "doi_url": "https://doi.org/10.12659/msm.881698", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/21455114/", "url": "https://h2medicine.org/studies/study-chuai-2011-possible-prevention-strategy-radiation/", "methods": [ "inhalation", "saline-iv" ], "indications": [ "cancer" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2011 · Chuai — A Possible Prevention Strategy of Radiation Pneumonitis: Combine Radiotherapy with Aerosol Inhalation of Hydrogen-Rich Solution", "summary": "This theoretical paper proposes that combining radiotherapy with aerosol inhalation of hydrogen-rich physiological saline could reduce radiation pneumonitis — a serious complication of lung cancer radiotherapy — by exploiting H₂'s ability to scavenge the hydroxyl radicals that cause most radiation-induced cell damage. This is a hypothesis paper, not a clinical or experimental study; no patient data are presented. (Medical Science Monitor, 2011.)", "assessment": "This is a theoretical/hypothesis paper — no experiments or patient data are presented. It is not a clinical or preclinical study. The scientific reasoning is internally consistent and grounded in prior H₂ research, but the hypothesis has not been experimentally validated in this paper. Honest note: hypothesis papers are an important part of the scientific process, but they do not constitute proof of efficacy. The clinical utility of H₂ aerosol inhalation for radiation pneumonitis prevention requires dedicated clinical trials to establish safety and efficacy in humans.", "abstract": "Radiotherapy is an important modality of cancer treatment. Radiation pneumonitis is a major obstacle to increasing the radiation dose in radiotherapy, and it is important to prevent this radiation-induced complication. Recent studies show that hydrogen has a potential as an effective and safe radioprotective agent by selectively reducing hydroxyl and peroxynitrite radicals. Since most of the ionizing radiation-induced cellular damage is caused by hydroxyl radicals, we hypothesize that a treatment combining radiotherapy with aerosol inhalation of a hydrogen-rich solution may be an effective and novel prevention strategy for radiation pneumonitis (hydrogen is explosive, while a hydrogen-rich solution such as physiological saline saturated with molecular hydrogen is safer).
", "conclusion": "Recent studies show that hydrogen has a potential as an effective and safe radioprotective agent by selectively reducing hydroxyl and peroxynitrite radicals. Since most of the ionizing radiation-induced cellular damage is caused by hydroxyl radicals, we hypothesize that a treatment combining radiotherapy with aerosol inhalation of a hydrogen-rich solution may be an effective and novel prevention s" }, { "pmid": "21335650", "year": 2011, "title": "Production of clinically useful positron emitter beams during carbon ion deceleration.", "title_en": null, "title_de": "Erzeugung klinisch nutzbarer Positronenstrahler-Strahlen während der Abbremsung von Kohlenstoffionen", "journal": "Physics in medicine and biology", "authors": "Lazzeroni et al.", "author_search": "lazzeroni lazzeroni", "doi": "10.1088/0031-9155/56/6/005", "doi_url": "https://doi.org/10.1088/0031-9155/56/6/005", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/21335650/", "url": "https://h2medicine.org/studies/study-lazzeroni-2011-production-clinically-useful-positron/", "methods": [ "unspecified" ], "indications": [ "liver", "cancer", "skin-aging" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2011 · Lazzeroni — Production of Clinically Useful Positron Emitter Beams During Carbon Ion Deceleration", "summary": "This radiation physics study models how to produce high-energy carbon-11 (¹¹C) fragments from a primary ¹²C beam for simultaneous cancer treatment and PET imaging — and finds that hydrogen-rich materials such as liquid hydrogen and polyethylene are the most efficient decelerators for this process. The mention of hydrogen here is entirely about nuclear physics, not about molecular hydrogen (H₂) therapy. (Physics in Medicine and Biology, 2011.)", "assessment": "This is a computational/theoretical physics study in radiation oncology engineering. It has no relevance to molecular hydrogen therapy. The word „hydrogen“ refers exclusively to hydrogen atoms as a component of nuclear physics decelerating materials. Honest note: this paper should not be cited in support of any H₂ health claim. It belongs to medical physics and particle therapy engineering, not H₂ biomedicine.", "abstract": "In external beam radiation therapy, radioactive beams offer the best clinical solution to simultaneously treat and in vivo monitor the dose delivery and tumor response using PET or PET-CT imaging. However, difficulties mainly linked to the low production efficiency have so far limited their use. This study is devoted to the analysis of the production of high energy (11)C fragments, preferably by projectile fragmentation of a stable monodirectional and monoenergetic primary (12)C beam in different absorbing materials (decelerators) in order to identify the optimal elemental composition. The study was performed using the Monte Carlo code SHIELD-HIT07. The track length and fluence of generated secondary particles were scored in a uniform absorber of 300 cm length and 10 cm radius, divided into slices of 1 cm thickness. The (11)C fluence build-up and mean energy variation with increasing decelerator depth are presented. Furthermore, the fluence of the secondary (11)C beam was studied as a function of its mean energy and the corresponding remaining range in water. It is shown that the maximum (11)C fluence build-up is high in compounds where the fraction by weight of hydrogen is high, being the highest in liquid hydrogen. Furthermore, a cost effective alternative solution to the single medium initially envisaged is presented: a two-media decelerator that comprises a first liquid hydrogen section followed by a second decelerating section made of a hydrogen-rich material, such as polyethylene (C(2)H(4)). The purpose of the first section is to achieve a fast initial (11)C fluence build-up, while the second section is primarily designed to modulate the mean energy of the generated (11)C beam in order to reach the tumor depth. Finally, it was demonstrated that, if the intensity of the primary (12)C beam can be increased by an order of magnitude, a sufficient intensity of the secondary (11)C beam is achieved for therapy and subsequent therapeutic PET imaging sessions. Such an increase in the intensity might be easily achieved with a superconducting cyclotron.", "conclusion": "Finally, it was demonstrated that, if the intensity of the primary (12)C beam can be increased by an order of magnitude, a sufficient intensity of the secondary (11)C beam is achieved for therapy and subsequent therapeutic PET imaging sessions. Such an increase in the intensity might be easily achieved with a superconducting cyclotron." }, { "pmid": "21269826", "year": 2011, "title": "Quinazolines with intra-molecular hydrogen bonding scaffold (iMHBS) as PI3K/mTOR dual inhibitors.", "title_en": null, "title_de": "Chinazoline mit intramolekularem Wasserstoffbrücken-Gerüst (iMHBS) als duale PI3K/mTOR-Inhibitoren", "journal": "Bioorganic & medicinal chemistry letters", "authors": "Liu et al.", "author_search": "liu liu", "doi": "10.1016/j.bmcl.2010.12.026", "doi_url": "https://doi.org/10.1016/j.bmcl.2010.12.026", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/21269826/", "url": "https://h2medicine.org/studies/study-liu-2011-quinazolines-intra-bonding-scaffold/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2011 · Liu — Quinazolines with Intra-Molecular Hydrogen Bonding Scaffold (iMHBS) as PI3K/mTOR Dual Inhibitors", "summary": "This medicinal chemistry study designs and synthesises a series of quinazoline molecules that use intra-molecular hydrogen bonding to form a pseudo-ring structure, acting as potent dual inhibitors of PI3K and mTOR — two kinases central to cancer cell proliferation and survival. The „hydrogen bonding“ in this paper refers to chemical bonds between atoms within drug molecules, not to molecular hydrogen (H₂) gas therapy. (Bioorganic & Medicinal Chemistry Letters, 2011.)", "assessment": "This is an in-vitro medicinal chemistry study. It has no connection to molecular hydrogen (H₂) therapy. The term „hydrogen“ in this paper refers exclusively to intra-molecular hydrogen bonds — a ubiquitous chemical interaction — within synthetic drug molecules. Honest note: this paper does not provide any evidence for or against H₂ water or H₂ gas as a health intervention. It is cancer drug discovery research and should not be cited in an H₂ medicine context.", "abstract": "Intra-molecular hydrogen bonding was introduced to the quinazoline motif to form a pseudo ring (intra-molecular H-bond scaffold, iMHBS) to mimic our previous published core structures, pyrido[2.3-D]pyrimidin-7-one and pteridinone, as PI3K/mTOR dual inhibitors. This design results in potent PI3K/mTOR dual inhibitors and the purposed intra-molecular hydrogen bonding structure is well supported by co-crystal structure in PI3Kγ enzyme. In addition, a novel synthetic route was developed for these analogs.", "conclusion": "This design results in potent PI3K/mTOR dual inhibitors and the purposed intra-molecular hydrogen bonding structure is well supported by co-crystal structure in PI3Kγ enzyme. In addition, a novel synthetic route was developed for these analogs." }, { "pmid": "21215337", "year": 2011, "title": "Perfusion electrodeposition of calcium phosphate on additive manufactured titanium scaffolds for bone engineering.", "title_en": null, "title_de": "Perfusions-Elektrodeposition von Calciumphosphat auf additiv gefertigten Titangerüsten für das Knochen-Engineering", "journal": "Acta biomaterialia", "authors": "Chai et al.", "author_search": "chai chai", "doi": "10.1016/j.actbio.2010.12.032", "doi_url": "https://doi.org/10.1016/j.actbio.2010.12.032", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/21215337/", "url": "https://h2medicine.org/studies/study-chai-2011-perfusion-electrodeposition-calcium-phosphate/", "methods": [ "inhalation" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2011 · Chai — Perfusion Electrodeposition of Calcium Phosphate on Additive Manufactured Titanium Scaffolds for Bone Engineering", "summary": "This biomaterials engineering study develops a perfusion-based electrodeposition system to uniformly coat 3D-printed titanium bone scaffolds with hydroxyapatite — a calcium phosphate mineral that promotes bone cell adhesion and growth — while addressing hydrogen gas removal as a technical process challenge. This is bone engineering research; the hydrogen mentioned is an unwanted electrochemical byproduct, not a therapeutic agent. (Acta Biomaterialia, 2011.)", "assessment": "This is an in-vitro biomaterials engineering study. Hydrogen gas appears here only as an unwanted electrochemical byproduct that must be managed during coating deposition — it is not a therapeutic agent. Honest note: this paper has no relevance to H₂ therapy and should not be cited in that context. It is valid biomedical engineering research on bone implant coatings. All outcomes are from laboratory testing; clinical performance in living bone would require animal and human studies.", "abstract": "A perfusion electrodeposition (P-ELD) system was reported to functionalize additive manufactured Ti6Al4V scaffolds with a calcium phosphate (CaP) coating in a controlled and reproducible manner. The effects and interactions of four main process parameters - current density (I), deposition time (t), flow rate (f) and process temperature (T) - on the properties of the CaP coating were investigated. The results showed a direct relation between the parameters and the deposited CaP mass, with a significant effect for t (P=0.001) and t-f interaction (P=0.019). Computational fluid dynamic analysis showed a relatively low electrolyte velocity within the struts and a high velocity in the open areas within the P-ELD chamber, which were not influenced by a change in f. This is beneficial for promoting a controlled CaP deposition and hydrogen gas removal. Optimization studies showed that a minimum t of 6 h was needed to obtain complete coating of the scaffold regardless of I, and the thickness was increased by increasing I and t. Energy-dispersive X-ray and X-ray diffraction analysis confirmed the deposition of highly crystalline synthetic carbonated hydroxyapatite under all conditions (Ca/P ratio=1.41). High cell viability and cell-material interactions were demonstrated by in vitro culture of human periosteum derived cells on coated scaffolds. This study showed that P-ELD provides a technological tool to functionalize complex scaffold structures with a biocompatible CaP layer that has controlled and reproducible physicochemical properties suitable for bone engineering.", "conclusion": "High cell viability and cell-material interactions were demonstrated by in vitro culture of human periosteum derived cells on coated scaffolds. This study showed that P-ELD provides a technological tool to functionalize complex scaffold structures with a biocompatible CaP layer that has controlled and reproducible physicochemical properties suitable for bone engineering." }, { "pmid": "20851533", "year": 2011, "title": "Hydrogen therapy may reduce the risks related to radiation-induced oxidative stress in space flight.", "title_en": null, "title_de": "Die Wasserstofftherapie könnte die mit strahlungsinduziertem oxidativem Stress verbundenen Risiken bei der Raumfahrt reduzieren", "journal": "Medical hypotheses", "authors": "Schoenfeld et al.", "author_search": "schoenfeld schoenfeld", "doi": "10.1016/j.mehy.2010.08.046", "doi_url": "https://doi.org/10.1016/j.mehy.2010.08.046", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/20851533/", "url": "https://h2medicine.org/studies/study-schoenfeld-2011-may-reduce-risks-related/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "metabolic", "cancer", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2011 · Schoenfeld — Hydrogen Therapy May Reduce the Risks Related to Radiation-Induced Oxidative Stress in Space Flight", "summary": "This hypothesis paper proposes that astronauts exposed to cosmic radiation during space missions could benefit from H₂ therapy — via inhalation or hydrogen-rich drinking water — to counteract the oxidative and DNA damage caused by cosmic radiation. This is a theoretical proposal drawing on H₂'s established antioxidant properties; no experiments or patient data are presented. (Medical Hypotheses, 2011.)", "assessment": "This is a hypothesis paper published in Medical Hypotheses, a journal specifically devoted to speculative scientific ideas. No experiments are conducted, no data are presented. The reasoning is scientifically coherent and the idea is plausible given H₂'s antioxidant profile, but remains completely unvalidated experimentally. Whether H₂ supplementation would actually reduce radiation-induced cancer risk or other adverse events in astronauts would require rigorous animal studies under simulated space radiation conditions, followed by human clinical trials — none of which are presented here. This paper should be understood as a research suggestion, not as evidence of efficacy.", "abstract": "Cosmic radiation is known to induce DNA and lipid damage associated with increased oxidative stress and remains a major concern in space travel. Hydrogen, recently discovered as a novel therapeutic medical gas in a variety of biomedical fields, has potent antioxidant and anti-inflammatory activities. It is expected that space mission activities will increase in coming years both in numbers and duration. It is therefore important to estimate and prevent the risks encountered by astronauts due to oxidative stress prior to developing clinical symptoms of disease. We hypothesize that hydrogen administration to the astronauts by either inhalation or drinking hydrogen-rich water may potentially yield a novel and feasible preventative/therapeutic strategy to prevent radiation-induced adverse events.", "conclusion": "It is therefore important to estimate and prevent the risks encountered by astronauts due to oxidative stress prior to developing clinical symptoms of disease. We hypothesize that hydrogen administration to the astronauts by either inhalation or drinking hydrogen-rich water may potentially yield a novel and feasible preventative/therapeutic strategy to prevent radiation-induced adverse events." }, { "pmid": "21166060", "year": 2010, "title": "[Research advances on hydrogen therapy in nervous system diseases].", "title_en": null, "title_de": "Forschungsfortschritte zur Wasserstofftherapie bei Erkrankungen des Nervensystems", "journal": "Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences", "authors": "Hong et al.", "author_search": "hong hong", "doi": "10.3785/j.issn.1008-9292.2010.06.015", "doi_url": "https://doi.org/10.3785/j.issn.1008-9292.2010.06.015", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/21166060/", "url": "https://h2medicine.org/studies/study-hong-2010-research-advances-nervous-system/", "methods": [ "unspecified" ], "indications": [ "neurology", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2010 · Hong — Research Advances on Hydrogen Therapy in Nervous System Diseases", "summary": "This review summarises experimental evidence that molecular hydrogen (H₂) exerts significant protective effects in various neurological diseases — including ischaemia, hypoxia, neurodegeneration, and spinal cord injury — through anti-oxidative, anti-inflammatory, and anti-apoptotic mechanisms. The review draws exclusively on animal and cell studies; clinical evidence in humans is not yet available. (Journal of Zhejiang University, Medical Sciences, 2010.)", "assessment": "This is a narrative review of preclinical (animal and cell) studies on H₂ in neurological diseases. It does not present new data; it synthesises existing experimental literature available as of 2010. The conclusion that H₂ has significant therapeutic effects in neurological diseases refers to animal and cell culture models only — this is not established in human clinical trials. Honest note: the mechanistic rationale is sound and the preclinical evidence is internally consistent, but the translation from animal neurology models to human patients remains a significant open question. The paper is a useful entry point for the neuroprotective H₂ literature but must not be cited as proof of human clinical benefit.", "abstract": "Oxidative stress plays a pivotal role in the pathogenesis of varied nervous system diseases. Recent studies have demonstrated that hydrogen has selective antioxidative effect. It selectively reduces the hydroxyl radical (*OH) and peroxynitrite (ONOO(-)), the most cytotoxic of reactive oxygen species (ROS); however, it does not affect other ROS, which play important physiological roles at low concentrations. A large body of experimental studies has proved that hydrogen, through anti-oxidation, anti-inflammatory and inhibiting apoptosis, has a significant therapeutic effect in various neurological diseases, such as ischemia, hypoxia, degeneration and spinal cord contusion. It provides us with a new clinical method for the prevention and treatment of neurological diseases.", "conclusion": "A large body of experimental studies has proved that hydrogen, through anti-oxidation, anti-inflammatory and inhibiting apoptosis, has a significant therapeutic effect in various neurological diseases, such as ischemia, hypoxia, degeneration and spinal cord contusion. It provides us with a new clinical method for the prevention and treatment of neurological diseases." }, { "pmid": "20708922", "year": 2010, "title": "Computational glycoscience: characterizing the spatial and temporal properties of glycans and glycan-protein complexes.", "title_en": null, "title_de": "Computergestützte Glykowissenschaft: Charakterisierung der räumlichen und zeitlichen Eigenschaften von Glykanen und Glykan-Protein-Komplexen.", "journal": "Current opinion in structural biology", "authors": "Woods et al.", "author_search": "woods woods", "doi": "10.1016/j.sbi.2010.07.005", "doi_url": "https://doi.org/10.1016/j.sbi.2010.07.005", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/20708922/", "url": "https://h2medicine.org/studies/study-woods-2010-computational-glycoscience-characterizing-spatial/", "methods": [ "drinking-hrw" ], "indications": [ "other" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2010 · Woods — Computational glycoscience: characterizing the spatial and temporal properties of glycans and glycan-protein complexes.", "summary": "This review surveys computational methods — molecular dynamics simulations and virtual ligand screening — for studying how sugar chains (glycans) bind to proteins. The authors describe what computer modelling adds to experimental structural biology: insight into hydrogen bond fluctuations, water residence times, and free-energy changes during glycan binding. Note: this paper does not involve hydrogen (H₂) therapy; it appears in a hydrogen-related database because the word „hydrogen” occurs in the biochemical context of hydrogen bonds.", "assessment": "This is a literature review in computational structural biology — not a study of molecular hydrogen (H₂) therapy. It has no relevance to the therapeutic use of H₂ as an antioxidant or anti-inflammatory agent. The paper is technically sound within its own field, but its appearance in an H₂ study database is an indexing artefact. No therapeutic claims about H₂ water or H₂ inhalation can be derived from this publication.", "abstract": "Modern computational methods offer the tools to provide insight into the structural and dynamic properties of carbohydrate-protein complexes, beyond that provided by experimental structural biology. Dynamic properties such as the fluctuation of inter-molecular hydrogen bonds, the residency times of bound water molecules, side chain motions and ligand flexibility may be readily determined computationally. When taken with respect to the unliganded states, these calculations can also provide insight into the entropic and enthalpic changes in free energy associated with glycan binding. In addition, virtual ligand screening may be employed to predict the three dimensional (3D) structures of carbohydrate-protein complexes, given 3D structures for the components. In principle, the 3D structure of the protein may itself be derived by modeling, leading to the exciting--albeit high risk--realm of virtual structure prediction. This latter approach is appealing, given the difficulties associated with generating experimental 3D structures for some classes of glycan binding proteins; however, it is also the least robust. An unexpected outcome of the development of algorithms for modeling carbohydrate-protein interactions has been the discovery of errors in reported experimental 3D structures and a heightened awareness of the need for carbohydrate-specific computational tools for assisting in the refinement and curation of carbohydrate-containing crystal structures. Here we present a summary of the basic strategies associated with employing classical force field based modeling approaches to problems in glycoscience, with a focus on identifying typical pitfalls and limitations. This is not an exhaustive review of the current literature, but hopefully will provide a guide for the glycoscientist interested in modeling carbohydrates and carbohydrate-protein complexes, as well as the computational chemist contemplating such tasks.", "conclusion": "Here we present a summary of the basic strategies associated with employing classical force field based modeling approaches to problems in glycoscience, with a focus on identifying typical pitfalls and limitations. This is not an exhaustive review of the current literature, but hopefully will provide a guide for the glycoscientist interested in modeling carbohydrates and carbohydrate-protein compl" }, { "pmid": "20423296", "year": 2010, "title": "Amyloid formation in surfactants and alcohols: membrane mimetics or structural switchers?", "title_en": null, "title_de": "Amyloidbildung in Tensiden und Alkoholen: Membranmimetika oder strukturelle Umschalter?", "journal": "Current protein & peptide science", "authors": "Otzen", "author_search": "otzen otzen", "doi": "10.2174/138920310791330622", "doi_url": "https://doi.org/10.2174/138920310791330622", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/20423296/", "url": "https://h2medicine.org/studies/study-otzen-2010-amyloid-formation-surfactants-alcohols/", "methods": [ "unspecified" ], "indications": [ "sports-exercise" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2010 · Otzen — Amyloid formation in surfactants and alcohols: membrane mimetics or structural switchers?", "summary": "This biochemistry review examines how anionic detergents (e.g. SDS) and fluorinated alcohols (e.g. TFE) influence protein aggregation into amyloid fibrils. The author argues these solvents act less as true membrane mimics and more as agents that shift the balance between alpha-helical and beta-sheet structures, favouring intermolecular beta-sheet formation. Note: this paper has no connection to molecular hydrogen (H₂) therapy; its appearance in an H₂ database is an indexing artefact.", "assessment": "This is a literature review in protein biophysics with no relevance to molecular hydrogen (H₂) therapy, H₂-rich water, or H₂ inhalation. It is technically sound within its own field but was incorrectly indexed in an H₂ study database. No conclusions about H₂ as a health intervention can be drawn from this paper.", "abstract": "Attempts to understand the biophysical foundations and biochemical consequences of protein aggregation process are greatly aided by conditions which provide either robust and reliable reaction conditions or constitute mimics of the physiological conditions. While both anionic surfactants such as SDS and fluorinated alcohols such as TFE are often championed as membrane mimics in one way or another, it is probably fair to say that their greatest advantage is to facilitate protein aggregation under simple and well-defined solvent conditions which are compatible with a plethora of biophysical techniques. In contrast to the biological membrane, whose chemical complexity and physical heterogeneity gives rise to a multitude of possible interactions with proteins, SDS and TFE exert a surprisingly versatile effect on proteins by a combination of two opposing forces: a weakening of protein-protein hydrophobic interactions and a strengthening of inter- and intra-molecular hydrogen bonding. This invariably gives rise to a concentration range (typically 0.5-1 mM SDS and 20-30% TFE) which favours intermolecular beta-sheet formation. I discuss a number of examples of this behaviour, and present recent investigations based on a combination of calorimetric, spectroscopic and Small Angle X-ray scattering techniques. Together these provide a structural and stoichiometric picture of the different species involved in SDS-mediated protein aggregation, driven by the hydrophobic bonds formed when SDS clusters on different proteins form a contiguous micelle by protein association. Higher-order aggregates are formed by protein regions linking these shared micelles, providing a flexible bead-on-a-string that grows in a step-wise fashion and leads to worm-like fibrillar structures. Despite the unique features displayed in different aggregating systems, there are clear parallels between membrane-mediated aggregation and aggregation in SDS and TFE in terms of modulation between alpha-helical and beta-sheet structures depending on the ratio between protein and amphiphile.", "conclusion": "Higher-order aggregates are formed by protein regions linking these shared micelles, providing a flexible bead-on-a-string that grows in a step-wise fashion and leads to worm-like fibrillar structures. Despite the unique features displayed in different aggregating systems, there are clear parallels between membrane-mediated aggregation and aggregation in SDS and TFE in terms of modulation between " }, { "pmid": "20347528", "year": 2010, "title": "Hydrogen as a novel and effective treatment of acute carbon monoxide poisoning.", "title_en": null, "title_de": "Wasserstoff als neuartige und wirksame Behandlung der akuten Kohlenmonoxidvergiftung.", "journal": "Medical hypotheses", "authors": "Shen et al.", "author_search": "shen shen", "doi": "10.1016/j.mehy.2010.02.029", "doi_url": "https://doi.org/10.1016/j.mehy.2010.02.029", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/20347528/", "url": "https://h2medicine.org/studies/study-shen-2010-effective-acute-carbon-monoxide/", "methods": [ "inhalation" ], "indications": [ "neurology", "immune-system", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2010 · Shen — Hydrogen as a novel and effective treatment of acute carbon monoxide poisoning.", "summary": "This hypothesis paper proposes that inhaled molecular hydrogen (H₂) could be an effective treatment for acute carbon monoxide (CO) poisoning. The authors reason that since CO poisoning triggers oxidative stress, free radical damage and neuroinflammation — and since H₂ has been shown to selectively neutralise the most damaging radicals (hydroxyl radical, peroxynitrite) — H₂ therapy may protect the brain from CO-induced injury. This is a theoretical proposal, not a clinical or animal study.", "assessment": "This is a theoretical hypothesis paper — not a clinical trial or animal experiment. It contains no original data on H₂ and CO poisoning. The mechanistic logic is reasonable: CO poisoning and ischaemia-reperfusion share oxidative pathways, and H₂ has shown antioxidant effects in the latter. However, this is not a human study, and the hypothesis had not been experimentally validated at the time of publication. It represents a starting point for investigation, not a demonstrated treatment.", "abstract": "Hydrogen is a major component of interstellar space and the fuel that sustains the stars. However, it is seldom regarded as a therapeutic gas. A recent study provided evidence that hydrogen inhalation exerted antioxidant and anti-apoptotic effects and protected the brain against ischemia-reperfusion injury by selectively reducing hydroxyl radical and peroxynitrite. It has been known that the mechanisms underlying the brain injury after acute carbon monoxide poisoning are interwoven with multiple factors including oxidative stress, free radicals, and neuronal nitric oxide synthase as well as abnormal inflammatory responses. Studies have shown that free radical scavengers can improve the neural damage. Based on the findings abovementioned, we hypothesize that hydrogen therapy may be an effective, simple, economic and novel strategy in the treatment of acute carbon monoxide poisoning.", "conclusion": "Studies have shown that free radical scavengers can improve the neural damage. Based on the findings abovementioned, we hypothesize that hydrogen therapy may be an effective, simple, economic and novel strategy in the treatment of acute carbon monoxide poisoning." }, { "pmid": "20216947", "year": 2010, "title": "Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome - an open label pilot study", "title_en": null, "title_de": "Wirksamkeit von wasserstoffreichem Wasser auf den Antioxidans-Status von Personen mit potenziellem metabolischem Syndrom — eine offene Pilotstudie", "journal": "Journal of Clinical Biochemistry and Nutrition", "authors": "Nakao et al.", "author_search": "nakao nakao", "doi": "10.3164/jcbn.09-100", "doi_url": "https://doi.org/10.3164/jcbn.09-100", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/20216947/", "url": "https://h2medicine.org/studies/study-nakao-2010-hydrogen-rich-water-metabolic-syndrome-antioxidant/", "methods": [ "drinking-hrw" ], "indications": [ "metabolic", "cardiovascular", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2010 · Nakao — Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome - an open label pilot study", "summary": "The magnesium-stick method, scientifically documented. Hydrogen-rich water generated by a magnesium stick (Mg + 2H₂O → Mg(OH)₂ + H₂) increased the body's own protective enzyme SOD by +39 % over 8 weeks and lowered oxidative stress (TBARS) by −43 % in people with early metabolic syndrome. (J. Clin. Biochem. Nutr., 2010.)", "assessment": "The scientific anchor for the magnesium method of generating hydrogen-rich water. While Ohsawa shows the mechanism and Kajiyama the clinical effect with a strong design, Nakao demonstrates that even the simplest, everyday generation method delivers measurable antioxidant effects. Limitation, stated honestly: open-label pilot without placebo control and only 20 subjects — lower evidential weight; expectancy effects not ruled out. As a „proof of concept“ for the Mg method, however, it is well suited.", "abstract": "Metabolic syndrome is characterized by cardiometabolic risk factors that include obesity, insulin resistance, hypertension and dyslipidemia. Oxidative stress is known to play a major role in the pathogenesis of metabolic syndrome. The objective of this study was to examine the effectiveness of hydrogen rich water (1.5-2 L/day) in an open label, 8-week study on 20 subjects with potential metabolic syndrome. Hydrogen rich water was produced, by placing a metallic magnesium stick into drinking water (hydrogen concentration; 0.55-0.65 mM), by the following chemical reaction; Mg + 2H(2)O --> Mg (OH)(2) + H(2). The consumption of hydrogen rich water for 8 weeks resulted in a 39% increase (p<0.05) in antioxidant enzyme superoxide dismutase (SOD) and a 43% decrease (p<0.05) in thiobarbituric acid reactive substances (TBARS) in urine. Further, subjects demonstrated an 8% increase in high density lipoprotein (HDL)-cholesterol and a 13% decrease in total cholesterol/HDL-cholesterol from baseline to week 4. There was no change in fasting glucose levels during the 8 week study. In conclusion, drinking hydrogen rich water represents a potentially novel therapeutic and preventive strategy for metabolic syndrome. The portable magnesium stick was a safe, easy and effective method of delivering hydrogen rich water for daily consumption by participants in the study.", "conclusion": "In conclusion, drinking hydrogen rich water represents a potentially novel therapeutic and preventive strategy for metabolic syndrome. The portable magnesium stick was a safe, easy and effective method of delivering hydrogen rich water for daily consumption by participants in the study." }, { "pmid": "21275114", "year": 2010, "title": "The hypothesis of an effective safe and novel radioprotective agent: hydrogen-rich solution.", "title_en": null, "title_de": "Die Hypothese eines wirksamen, sicheren und neuartigen Radioprotektors: wasserstoffreiche Lösung.", "journal": "The West Indian medical journal", "authors": "Qian et al.", "author_search": "qian qian", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/21275114/", "url": "https://h2medicine.org/studies/study-qian-2010-hypothesis-effective-safe-radioprotective/", "methods": [ "saline-iv" ], "indications": [ "neurology", "cancer", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2010 · Qian — The hypothesis of an effective safe and novel radioprotective agent: hydrogen-rich solution.", "summary": "This theory paper proposes that hydrogen-rich saline could serve as a safe radioprotective agent — protecting cells from ionising radiation damage by selectively scavenging hydroxyl radicals. The authors note that most radiation damage is caused by reactive oxygen species, and that H₂-rich saline is far safer than explosive H₂ gas, making it a potentially practical clinical tool. This is a theoretical proposal, not an experimental study.", "assessment": "This is a preclinical theory paper — it contains no experimental data and makes no human health claims. The mechanistic reasoning (radiation → ROS → hydroxyl radicals → H₂ as selective scavenger) is plausible and scientifically grounded in the broader H₂ literature, but the specific application to radiation protection had not been tested at the time of writing. This is not evidence that H₂ saline protects humans from radiation; it is a reasoned call for experimental investigation.", "abstract": "Most ionizing radiation-induced damage is caused by radical oxygen species (ROS). Some radioprotectors, such as amifostine, exert radioprotective effects by scavenging radical oxygen species. Recent studies show that hydrogen (H) has antioxidant activities that protect the brain and intestine against ischaemia-reperfusion injury and stroke by selectively reducing hydroxyl and peroxynitrite radicals. However it is seldom regarded as a radioprotective agent. In like manner we hypothesize that hydrogen may be an effective, specific and novel radioprotective agent. But H2 is explosive, while hydrogen-rich solution (solution such as physiological saline saturated with molecular hydrogen) is safer.", "conclusion": "In like manner we hypothesize that hydrogen may be an effective, specific and novel radioprotective agent. But H2 is explosive, while hydrogen-rich solution (solution such as physiological saline saturated with molecular hydrogen) is safer." }, { "pmid": "21042740", "year": 2010, "title": "Antitumor effects of nano-bubble hydrogen-dissolved water are enhanced by coexistent platinum colloid and the combined hyperthermia with apoptosis-like cell death.", "title_en": null, "title_de": "Antitumorwirkungen von Wasser mit gelöstem Nanobläschen-Wasserstoff werden durch koexistierendes Platin-Kolloid und die kombinierte Hyperthermie mit apoptoseähnlichem Zelltod verstärkt.", "journal": "Oncology reports", "authors": "Asada et al.", "author_search": "asada asada", "doi": "10.3892/or_00001006", "doi_url": "https://doi.org/10.3892/or_00001006", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/21042740/", "url": "https://h2medicine.org/studies/study-asada-2010-antitumor-nano-bubble-dissolved/", "methods": [ "drinking-hrw" ], "indications": [ "cancer", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2010 · Asada — Antitumor effects of nano-bubble hydrogen-dissolved water are enhanced by coexistent platinum colloid and the combined hyperthermia with apoptosis-like cell death.", "summary": "This laboratory (in-vitro/animal) study tested whether hydrogen-dissolved water — especially in combination with platinum colloid and mild heat (42 °C) — could inhibit the growth of tumour cells. Using Ehrlich ascites tumour cells, the researchers found that nano-bubble hydrogen water killed tumour cells, and this effect was substantially amplified when platinum colloid was added and when hyperthermia was applied. These are cell and animal laboratory results, not human data.", "assessment": "This is a preclinical in-vitro study using cultured tumour cells — not a human cancer trial. The results are interesting and mechanistically plausible (H₂ depletes ROS that tumour cells depend on), but the experimental conditions (nano-bubble water + platinum colloid + hyperthermia) are far from any clinical setting. No conclusions about cancer treatment in humans can be drawn from this study. The combination with hyperthermia and platinum colloid introduces multiple variables that make it difficult to attribute effects to H₂ alone.", "abstract": "In order to erase reactive oxygen species (ROS) related with the proliferation of tumor cells by reducing activity of hydrogen, we developed functional water containing nano-bubbles (diameters: <900 nm for 71%/population) hydrogen of 1.1-1.5 ppm (the theoretical maximum: 1.6 ppm) with a reducing ability (an oxidation-reduction potential -650 mV, normal water: +100-200 mV) using a microporous-filter hydrogen-jetting device. We showed that hydrogen water erased ROS indispensable for tumor cell growth by ESR/spin trap, the redox indicator CDCFH-DA assay, and was cytotoxic to Ehrlich ascites tumor cells as assessed by WST-8 assay, crystal violet dye stain and scanning electron microscopy, after 24-h or 48-h incubation sequent to warming at 37°C or 42°C. Hydrogen water supplemented with platinum colloid (0.3 ppm Pt in 4% polyvinylpyrrolidone) had more antitumor activity than hydrogen water alone, mineral water alone (15.6%), hydrogen water plus mineral water, or platinum colloid alone as observed by decreased cell numbers, cell shrinkage and pycnosis (nuclear condensation)/karyorrhexis (nuclear fragmentation) indicative of apoptosis, together with cell deformation and disappearance of microvilli on the membrane surface. These antitumor effects were promoted by combination with hyperthermia at 42°C. Thus, the nano-bubble hydrogen water with platinum colloid is potent as an anti-tumor agent.", "conclusion": "These antitumor effects were promoted by combination with hyperthermia at 42°C. Thus, the nano-bubble hydrogen water with platinum colloid is potent as an anti-tumor agent." }, { "pmid": "20858206", "year": 2010, "title": "Spontaneous adjustment mechanism in an RNA-binding protein: cooperation between energetic stabilization and target search enhancement.", "title_en": null, "title_de": "Spontaner Anpassungsmechanismus in einem RNA-bindenden Protein: Zusammenwirken von energetischer Stabilisierung und Verbesserung der Zielsuche.", "journal": "Protein and peptide letters", "authors": "Kurisaki et al.", "author_search": "kurisaki kurisaki", "doi": "10.2174/0929866511009011547", "doi_url": "https://doi.org/10.2174/0929866511009011547", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/20858206/", "url": "https://h2medicine.org/studies/study-kurisaki-2010-spontaneous-adjustment-mechanism-rna/", "methods": [ "unspecified" ], "indications": [ "neurology", "cancer" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2010 · Kurisaki — Spontaneous adjustment mechanism in an RNA-binding protein: cooperation between energetic stabilization and target search enhancement.", "summary": "This computational biology study used molecular dynamics simulation to analyse structural changes in an RNA-binding protein (NOVA) after it dissociates from its RNA target. The simulation revealed a spontaneous conformational change driven by intramolecular hydrogen bonds, which the authors propose enhances the protein's ability to find new RNA targets. Note: this paper has no connection to molecular hydrogen (H₂) therapy — it is a structural biology study.", "assessment": "This is a computational structural biology study with no relevance to molecular hydrogen (H₂) therapy. It models protein-RNA dynamics using molecular mechanics — hydrogen bonds in this context are standard chemical bonds between atoms, not dissolved H₂ gas. Its presence in an H₂ database is an indexing error. No health claims regarding H₂ can be derived from this publication.", "abstract": "We propose a novel concept associated with the relationship between structure and function in biomolecular systems. We performed a 75 nanoseconds molecular dynamics (MD) simulation for an RNA-binding protein, neuro-oncological ventral antigen (NOVA), and examined its physico-chemical properties. NOVA dissociated from the NOVA-RNA complex showed a large conformational change: formation of intra-molecular hydrogen bonds between the C-terminal region and the loop structure located at the middle of amino acid sequence. The free energy analysis suggests that the deformed structure is more stabilized in macromolecular crowding environment where the dielectric constant is smaller than 5. The solvent accessible surface area (SASA) analysis indicates that NOVA enhances the efficiency of association with RNA by changing the relative SASA for the target sequence in RNA molecules. Based on the obtained results, we propose a novel concept of spontaneous adjustment mechanism to explain the structural and energetic changes observed for NOVA in the free state.", "conclusion": "The solvent accessible surface area (SASA) analysis indicates that NOVA enhances the efficiency of association with RNA by changing the relative SASA for the target sequence in RNA molecules. Based on the obtained results, we propose a novel concept of spontaneous adjustment mechanism to explain the structural and energetic changes observed for NOVA in the free state." }, { "pmid": "20801581", "year": 2010, "title": "Oral administration of mannitol may be an effective treatment for ischemia-reperfusion injury.", "title_en": null, "title_de": "Die orale Verabreichung von Mannitol könnte eine wirksame Behandlung des Ischämie-Reperfusions-Schadens sein.", "journal": "Medical hypotheses", "authors": "Liu et al.", "author_search": "liu liu", "doi": "10.1016/j.mehy.2010.07.048", "doi_url": "https://doi.org/10.1016/j.mehy.2010.07.048", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/20801581/", "url": "https://h2medicine.org/studies/study-liu-2010-oral-administration-mannitol-may/", "methods": [ "inhalation", "saline-iv", "drinking-hrw" ], "indications": [ "liver", "neurology", "cardiovascular", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2010 · Liu — Oral administration of mannitol may be an effective treatment for ischemia-reperfusion injury.", "summary": "This hypothesis paper proposes that oral mannitol — a sugar alcohol that promotes bacterial hydrogen gas production in the colon — could protect organs from ischaemia-reperfusion injury by raising endogenous H₂ levels. The authors previously showed that intraperitoneal H₂-rich saline protects the brain, heart and intestine from reperfusion injury in rats, and now extend that logic to an oral mannitol strategy for boosting the body's own H₂ production. This is a theoretical proposal, not a clinical trial.", "assessment": "This is a hypothesis paper proposing oral mannitol as an indirect H₂ delivery strategy for ischaemia-reperfusion protection. It is not a clinical trial or controlled animal study. The mechanistic basis (colonic bacterial H₂ → blood H₂ → organ protection) is biologically plausible and consistent with the known biology of endogenous H₂. However, no efficacy data in humans are presented, and the leap from breath H₂ levels to organ protection against ischaemia is significant and untested here. It represents an interesting hypothesis for future investigation.", "abstract": "Inhalation of hydrogen gas has been proved to be an effective treatment for ischemia-reperfusion injury. There has been considerable evidence of hydrogen's protective effect to diseases related to oxidative injury, such as the ischemia-reperfusion injury of the brain, liver and heart. Our previous studies demonstrated that intraperitoneal injection of hydrogen-rich saline protected hypoxic-ischemic brain injury, myocardial and intestine ischemia-reperfusion injury in rats. Bacteria in the large intestinal can produce endogenous hydrogen, and our preliminary experiments revealed that oral administration of mannitol in humans and animals can significantly increase the level of endogenous hydrogen. Therefore, we speculated that oral administration of mannitol may be effective against ischemia-reperfusion injury, which is a convenient, effective and unique treatment for ischemia-reperfusion injury.", "conclusion": "Bacteria in the large intestinal can produce endogenous hydrogen, and our preliminary experiments revealed that oral administration of mannitol in humans and animals can significantly increase the level of endogenous hydrogen. Therefore, we speculated that oral administration of mannitol may be effective against ischemia-reperfusion injury, which is a convenient, effective and unique treatment for" }, { "pmid": "20570654", "year": 2010, "title": "Hydrogen gas treatment prolongs replicative lifespan of bone marrow multipotential stromal cells in vitro while preserving differentiation and paracrine potentials.", "title_en": null, "title_de": "Die Behandlung mit Wasserstoffgas verlängert die replikative Lebensspanne multipotenter Knochenmark-Stromazellen in vitro unter Erhaltung des Differenzierungs- und parakrinen Potenzials.", "journal": "Biochemical and biophysical research communications", "authors": "Kawasaki et al.", "author_search": "kawasaki kawasaki", "doi": "10.1016/j.bbrc.2010.06.009", "doi_url": "https://doi.org/10.1016/j.bbrc.2010.06.009", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/20570654/", "url": "https://h2medicine.org/studies/study-kawasaki-2010-prolongs-replicative-lifespan-bone/", "methods": [ "inhalation" ], "indications": [ "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2010 · Kawasaki — Hydrogen gas treatment prolongs replicative lifespan of bone marrow multipotential stromal cells in vitro while preserving differentiation and paracrine potentials.", "summary": "This in-vitro study found that exposing mesenchymal stem cells (MSCs) to 3 % hydrogen gas during laboratory expansion significantly prolonged their replicative lifespan and preserved their ability to differentiate and secrete therapeutic factors. The finding is relevant to regenerative medicine, where ex-vivo expansion of MSCs is limited by cellular ageing. Note: this is a cell culture study, not a human trial, and the mechanism turned out to be more complex than simple hydroxyl radical scavenging.", "assessment": "This is an in-vitro preclinical study — results were obtained in cell culture and cannot be directly transferred to humans. The finding that H₂ prolongs MSC lifespan without the expected drop in oxidative stress markers is a scientifically honest and important result: it suggests H₂'s anti-senescence action involves mechanisms beyond simple ROS neutralisation. The study opens interesting questions but does not establish clinical efficacy. It is a useful mechanistic stepping stone for regenerative medicine research.", "abstract": "Cell therapy with bone marrow multipotential stromal cells/mesenchymal stem cells (MSCs) represents a promising approach in the field of regenerative medicine. Low frequency of MSCs in adult bone marrow necessitates ex vivo expansion of MSCs after harvest; however, such a manipulation causes cellular senescence with loss of differentiation, proliferative, and therapeutic potentials of MSCs. Hydrogen molecules have been shown to exert organ protective effects through selective reduction of hydroxyl radicals. As oxidative stress is one of the key insults promoting cell senescence in vivo as well as in vitro, we hypothesized that hydrogen molecules prevent senescent process during MSC expansion. Addition of 3% hydrogen gas enhanced preservation of colony forming early progenitor cells within MSC preparation and prolonged the in vitro replicative lifespan of MSCs without losing differentiation potentials and paracrine capabilities. Interestingly, 3% hydrogen gas treatment did not decrease hydroxyl radical, protein carbonyl, and 8-hydroxydeoxyguanosine, suggesting that scavenging hydroxyl radical might not be responsible for these effects of hydrogen gas in this study.", "conclusion": "Addition of 3% hydrogen gas enhanced preservation of colony forming early progenitor cells within MSC preparation and prolonged the in vitro replicative lifespan of MSCs without losing differentiation potentials and paracrine capabilities. Interestingly, 3% hydrogen gas treatment did not decrease hydroxyl radical, protein carbonyl, and 8-hydroxydeoxyguanosine, suggesting that scavenging hydroxyl r" }, { "pmid": "20388631", "year": 2010, "title": "A novel bioactive haemodialysis system using dissolved dihydrogen (H2) produced by water electrolysis: a clinical trial.", "title_en": null, "title_de": "Ein neuartiges bioaktives Hämodialysesystem unter Verwendung von gelöstem Diwasserstoff (H₂), erzeugt durch Wasserelektrolyse: eine klinische Studie", "journal": "Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association", "authors": "Nakayama et al.", "author_search": "nakayama nakayama", "doi": "10.1093/ndt/gfq196", "doi_url": "https://doi.org/10.1093/ndt/gfq196", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/20388631/", "url": "https://h2medicine.org/studies/study-nakayama-2010-bioactive-haemodialysis-system-dissolved/", "methods": [ "inhalation" ], "indications": [ "cardiovascular", "cancer", "kidney-dialysis", "immune-system", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2010 · Nakayama et al. — A Novel Bioactive Haemodialysis System Using Dissolved Dihydrogen (H₂) Produced by Water Electrolysis: A Clinical Trial", "summary": "Adding dissolved molecular hydrogen to dialysis solution significantly reduced blood pressure and inflammatory markers in hemodialysis patients. In this 6-month clinical trial with 21 chronic kidney disease patients, H₂-enriched dialysis fluid lowered systolic blood pressure, reduced monocyte chemoattractant protein-1 (MCP-1), and reduced myeloperoxidase — with no adverse effects. (Nephrology, Dialysis, Transplantation, 2010.)", "assessment": "This is an early but substantive clinical trial for H₂ delivery via dialysis. The BP and inflammatory findings are statistically significant and clinically relevant for a population with poor treatment options. Limitations: No randomized control group — all 21 patients were switched to H₂-HD, so there is no concurrent control arm. This design cannot rule out regression to the mean or temporal confounds. The H₂ concentration (48 ppb) is relatively low compared to some other H₂ studies. The study is from a single center (Japan) and the sample is small. Despite these limitations, the safety profile and the magnitude of the BP response make this a meaningful proof-of-concept that warranted further investigation. The paper was published in a reputable nephrology journal.", "abstract": "BACKGROUND: Chronic inflammation in haemodialysis (HD) patients indicates a poor prognosis. However, therapeutic approaches are limited. Hydrogen gas (H(2)) ameliorates oxidative and inflammatory injuries to organs in animal models. We developed an HD system using a dialysis solution with high levels of dissolved H(2) and examined the clinical effects. METHODS: Dialysis solution with H(2) (average of 48 ppb) was produced by mixing dialysate concentrates and reverse osmosis water containing dissolved H(2) generated by a water electrolysis technique. Subjects comprised 21 stable patients on standard HD who were switched to the test HD for 6 months at three sessions a week. RESULTS: During the study period, no adverse clinical signs or symptoms were observed. A significant decrease in systolic blood pressure (SBP) before and after dialysis was observed during the study, and a significant number of patients achieved SBP <140 mmHg after HD (baseline, 21%; 6 months, 62%; P < 0.05). Changes in dialysis parameters were minimal, while significant decreases in levels of plasma monocyte chemoattractant protein 1 (P < 0.01) and myeloperoxidase (P < 0.05) were identified. CONCLUSIONS: Adding H(2) to haemodialysis solutions ameliorated inflammatory reactions and improved BP control. This system could offer a novel therapeutic option for control of uraemia.", "conclusion": "Adding H(2) to haemodialysis solutions ameliorated inflammatory reactions and improved BP control. This system could offer a novel therapeutic option for control of uraemia." }, { "pmid": "20298796", "year": 2010, "title": "Microbial equol production attenuates colonic methanogenesis and sulphidogenesis in vitro.", "title_en": null, "title_de": "Mikrobielle Equol-Produktion mildert kolische Methanogenese und Sulfidogenese in vitro.", "journal": "Anaerobe", "authors": "Bolca et al.", "author_search": "bolca bolca", "doi": "10.1016/j.anaerobe.2010.03.002", "doi_url": "https://doi.org/10.1016/j.anaerobe.2010.03.002", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/20298796/", "url": "https://h2medicine.org/studies/study-bolca-2010-microbial-equol-production-attenuates/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2010 · Bolca — Microbial equol production attenuates colonic methanogenesis and sulphidogenesis in vitro.", "summary": "This in-vitro gut microbiology study showed that equol-producing bacteria — which consume H₂ gas as part of converting the soy isoflavone daidzein into equol — competitively reduce methane and hydrogen sulphide production in the colon. When equol-producers are active, they draw down the shared H₂ pool that methanogens and sulphate-reducing bacteria depend on, decreasing production of the gases that cause bloating and flatulence. This is a laboratory study using simulated gut conditions, not a human trial.", "assessment": "This is an in-vitro gut microbiology study simulating colonic fermentation conditions — not a human trial. The results show that equol-producing bacteria competitively suppress methane and H₂S production by utilising the shared colonic H₂ pool. The paper is relevant to understanding endogenous H₂ metabolism in the gut (H₂ as a fermentation by-product) but does not involve therapeutic administration of molecular H₂. Results cannot be extrapolated to human digestive outcomes without clinical confirmation.", "abstract": "Hydrogen gas produced during colonic fermentation is excreted in breath and flatus, or removed by hydrogen-consuming bacteria such as methanogens and sulphate-reducing bacteria. However, recent research has shown that H2 is also consumed by equol-producing bacteria during the reduction of daidzein into equol. In this study, the interactions between methanogens, sulphate-reducing, and equol-producing bacteria were investigated under in vitro simulated intestinal conditions. In the presence of daidzein, the equol-producing bacterial consortium EPC4 gave rise to equol production in cultures of Methanobrevibacter smithii or Desulfovibrio sp. as well as in faecal samples with methanogenic or sulphate-reducing abilities. Moreover, this supplementation significantly (P<0.001) decreased the methanogenesis and sulphidogenesis. The attenuation did not occur in the absence of a daidzein source. Additionally, there was no influence of soy germ powder, daidzein or equol as such, excluding a possible inhibition by these compounds. Finally, a stronger decrease was observed with increasing amounts of EPC4 and a constant equol production, suggesting that the observed effect was only partly caused by the action of daidzein as a hydrogen sink. These findings are of relevance since abdominal discomfort such as bloating and flatulence, are related to colonic gas production, whereas equol has potential health benefits.", "conclusion": "Finally, a stronger decrease was observed with increasing amounts of EPC4 and a constant equol production, suggesting that the observed effect was only partly caused by the action of daidzein as a hydrogen sink. These findings are of relevance since abdominal discomfort such as bloating and flatulence, are related to colonic gas production, whereas equol has potential health benefits." }, { "pmid": "20031201", "year": 2010, "title": "A biodegradable polymer-based coating to control the performance of magnesium alloy orthopaedic implants.", "title_en": null, "title_de": "Eine biologisch abbaubare polymerbasierte Beschichtung zur Steuerung der Leistung von orthopädischen Implantaten aus Magnesiumlegierung.", "journal": "Biomaterials", "authors": "Wong et al.", "author_search": "wong wong", "doi": "10.1016/j.biomaterials.2009.11.111", "doi_url": "https://doi.org/10.1016/j.biomaterials.2009.11.111", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/20031201/", "url": "https://h2medicine.org/studies/study-wong-2010-biodegradable-polymer-coating-control/", "methods": [ "inhalation" ], "indications": [ "sports-exercise", "joints-rheumatology", "immune-system" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2010 · Wong — A biodegradable polymer-based coating to control the performance of magnesium alloy orthopaedic implants.", "summary": "This in-vitro and in-vivo study developed a biodegradable polymer coating for magnesium alloy bone implants to control their corrosion rate and reduce the accumulation of hydrogen gas during degradation. Uncoated magnesium implants corrode quickly and release H₂ gas in tissue — a clinical safety concern. The polymer coating slowed degradation, maintained bone mechanical properties, and in animal tests produced more new bone growth. Note: this paper is not about H₂ therapy — H₂ appears here as an unwanted by-product of implant corrosion.", "assessment": "This is a biomedical engineering study on orthopaedic implant materials — not a study of therapeutic molecular hydrogen. H₂ appears in this paper exclusively as an unwanted corrosion by-product that the researchers aimed to eliminate. The study is technically sound in its own domain (materials science, implant biocompatibility) and its presence in an H₂ database is an indexing artefact. No conclusions about H₂ as a health therapy can be drawn from this publication.", "abstract": "Magnesium and its alloys may potentially be applied as degradable metallic materials in orthopaedic implantations due to their degradability and resemblance to human cortical bone. However, the high corrosion rate and accumulation of hydrogen gas upon degradation hinders its clinical application. In this study, we adopt a new approach to control the corrosion rate by coating a controllable polymeric membrane fabricated by polycaprolactone and dichloromethane onto magnesium alloys, in which the pore size was controlled during the manufacturing process. The addition of the polymeric membrane was found to reduce the degradation rate of magnesium, and the bulk mechanical properties were shown to be maintained upon degradation. The in-vitro studies indicated good cytocompatibility of eGFP and SaOS-2 osteoblasts with the polymer-coated samples, which was not observed for the uncoated samples. The in-vivo study indicated that the uncoated sample degraded more rapidly than that of the polymer-coated samples. Although new bone formation was found on both samples, as determined by Micro-CT, higher volumes of new bone were observed on the polymer-coated samples. Histological analysis indicated no inflammation, necrosis or hydrogen gas accumulation on either of the samples during degradation. Collectively, these data suggest that the use of polymeric membrane may be potentially applied for future clinical use.", "conclusion": "Histological analysis indicated no inflammation, necrosis or hydrogen gas accumulation on either of the samples during degradation. Collectively, these data suggest that the use of polymeric membrane may be potentially applied for future clinical use." }, { "pmid": "19765780", "year": 2010, "title": "Failure of d-psicose absorbed in the small intestine to metabolize into energy and its low large intestinal fermentability in humans.", "title_en": null, "title_de": "Versagen von im Dünndarm absorbierter D-Psicose, in Energie verstoffwechselt zu werden, und ihre geringe Fermentierbarkeit im Dickdarm beim Menschen", "journal": "Metabolism: clinical and experimental", "authors": "Iida et al.", "author_search": "iida iida", "doi": "10.1016/j.metabol.2009.07.018", "doi_url": "https://doi.org/10.1016/j.metabol.2009.07.018", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/19765780/", "url": "https://h2medicine.org/studies/study-iida-2010-failure-psicose-absorbed-small/", "methods": [], "indications": [ "metabolic" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "breath-test", "headline": "2010 · Iida et al. — Failure of D-Psicose Absorbed in the Small Intestine to Metabolize into Energy and Its Low Large Intestinal Fermentability in Humans", "summary": "This nutrition study uses breath hydrogen as a standard fermentation marker to assess the metabolic fate of d-psicose (a rare sugar) in humans — it is not an H₂ therapy study. The finding is that d-psicose is poorly fermented and has an energy value below 1.6 kJ/g. Hydrogen-rich water and H₂ as a therapeutic agent are not investigated. (Metabolism: Clinical and Experimental, 2010.)", "assessment": "Off-topic for H₂ therapy. Breath hydrogen is used exclusively as a colonic fermentation marker in this food science study. No hydrogen-rich water, no H₂ inhalation therapy, no H₂ therapeutic intervention of any kind was applied. The source metadata classification (methods: „inhalation, drinking-hrw“) is incorrect. This study investigates the nutritional properties of a rare sugar, not molecular hydrogen medicine.", "abstract": "Experiments with rats have produced data on the metabolism and energy value of d-psicose; however, no such data have been obtained in humans. The authors assessed the availability of d-psicose absorbed in the small intestine by measuring carbohydrate energy expenditure (CEE) by indirect calorimetry. They measured the urinary excretion rate by quantifying d-psicose in urine for 48 hours. To examine d-psicose fermentation in the large intestine, the authors measured breath hydrogen gas and fermentability using 35 strains of intestinal bacteria. Six healthy subjects participated in the CEE test, and 14 participated in breath hydrogen gas and urine tests. d-Psicose fermentation subsequent to an 8-week adaptation period was also assessed by measuring hydrogen gas in 8 subjects. d-Psicose absorbed in the small intestine was not metabolized into energy, unlike glucose, because CEE did not increase within 3 hours of d-psicose ingestion (0.35 g/kg body weight [BW]). The accumulated d-psicose urinary excretion rates were around 70% for 0.34, 0.17, and 0.08 g/kg BW of ingested d-psicose. Low d-psicose fermentability was observed in intestinal bacteria and breath hydrogen gas tests, in which fructooligosaccharide (0.34, 0.17, and 0.08 g/kg BW) was used as a positive control because its available energy is known to be 8.4 kJ/g. Based on the results of the plot of breath hydrogen concentration vs calories ingested, the energy value of d-psicose was expected to be less than 1.6 kJ/g. Incremental d-psicose fermentability subsequent to an adaptation period was not observed.", "conclusion": "Based on the results of the plot of breath hydrogen concentration vs calories ingested, the energy value of d-psicose was expected to be less than 1.6 kJ/g. Incremental d-psicose fermentability subsequent to an adaptation period was not observed." }, { "pmid": "19725814", "year": 2010, "title": "Use of laser speckle flowgraphy in ocular blood flow research.", "title_en": null, "title_de": "Verwendung der Laser-Speckle-Flowgraphie in der Forschung zum okulären Blutfluss.", "journal": "Acta ophthalmologica", "authors": "Sugiyama et al.", "author_search": "sugiyama sugiyama", "doi": "10.1111/j.1755-3768.2009.01586.x", "doi_url": "https://doi.org/10.1111/j.1755-3768.2009.01586.x", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/19725814/", "url": "https://h2medicine.org/studies/study-sugiyama-2010-use-laser-speckle-flowgraphy/", "methods": [ "inhalation" ], "indications": [ "eye" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2010 · Sugiyama — Use of laser speckle flowgraphy in ocular blood flow research.", "summary": "This technical review describes laser speckle flowgraphy (LSFG), a non-contact imaging technique for measuring blood flow in the optic nerve head, choroid, retina and iris. The review explains the physics, calibration, and clinical protocols of LSFG — including a note that its blood flow index correlates with results from the „hydrogen gas clearance method”, an older calibration technique. Note: this paper has no connection to molecular hydrogen (H₂) therapy — the mention of hydrogen refers to a physiological measurement technique.", "assessment": "This is a technical ophthalmology methods review — it has no relevance to molecular hydrogen (H₂) therapy. The mention of „hydrogen gas” refers to an inert tracer used in blood flow physiology research, not to any therapeutic application of H₂. Its presence in an H₂ database is an indexing artefact. No health claims regarding H₂ can be derived from this publication.", "abstract": "Laser speckle flowgraphy (LSFG) allows for the quantitative estimation of blood flow in the optic nerve head, choroid, retina and iris in vivo. It was developed to facilitate the non-contact analysis of ocular blood flow in living eyes, utilizing the laser speckle phenomenon. The technique uses a fundus camera, a diode laser, an image sensor, an infrared charge-coupled device (CCD) camera and a high-resolution digital CCD camera. Normalized blur (NB), an approximate reciprocal of speckle contrast, represents an index of blood velocity, and shows a good correlation with tissue blood flow rates determined with the microsphere method in the retina, choroid or iris, as well as blood flow rates determined with the hydrogen gas clearance method in the optic nerve head. The square blur ratio (SBR), another index for quantitative estimation of blood velocity, is proportional to the square of the NB. The SBR is theoretically a more exact measurement which is proportional to velocity, whereas the NB is an approximation. Normalized blur was calculated in earlier versions of LSFG because of technical limitations; the SBR is used in current versions of the LSFG instrument. As these values are in arbitrary units, they should not be used to make comparisons between different eyes or different sites in an eye. Clinical protocols, calibration, evaluation procedures and possible limitations of the LSFG technique are described and the results of ocular blood flow studies using LSFG are briefly summarized. The LSFG method is suitable for monitoring the time-course of change in the tissue circulation at the same site in the same eye at various intervals, ranging from seconds to months. Unresolved issues concern the effect of pupil size on measurement results, the effects of various stimulations, and how to measure choroidal and retinal blood flow velocity separately without using the blue-component of argon laser.", "conclusion": "The LSFG method is suitable for monitoring the time-course of change in the tissue circulation at the same site in the same eye at various intervals, ranging from seconds to months. Unresolved issues concern the effect of pupil size on measurement results, the effects of various stimulations, and how to measure choroidal and retinal blood flow velocity separately without using the blue-component o" }, { "pmid": "19664884", "year": 2010, "title": "Hydrogen therapy may be an effective and specific novel treatment for acute radiation syndrome.", "title_en": null, "title_de": "Die Wasserstofftherapie könnte eine wirksame und spezifische neuartige Behandlung für das akute Strahlensyndrom sein.", "journal": "Medical hypotheses", "authors": "Liu et al.", "author_search": "liu liu", "doi": "10.1016/j.mehy.2009.07.017", "doi_url": "https://doi.org/10.1016/j.mehy.2009.07.017", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/19664884/", "url": "https://h2medicine.org/studies/study-liu-2010-may-effective-specific-acute/", "methods": [ "inhalation" ], "indications": [ "neurology", "cancer", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2010 · Liu — Hydrogen therapy may be an effective and specific novel treatment for acute radiation syndrome.", "summary": "This hypothesis paper proposes that inhaled molecular hydrogen (H₂) could be an effective treatment for acute radiation syndrome (ARS) — the life-threatening condition caused by high-dose whole-body irradiation. The authors argue that since more than half of radiation damage is caused by hydroxyl radicals, and since H₂ selectively scavenges hydroxyl radicals, H₂ therapy could specifically protect cells from radiation damage. This is a theoretical proposal, not an experimental study.", "assessment": "This is a theoretical hypothesis paper with no original experimental data on H₂ and acute radiation syndrome. The mechanistic reasoning is plausible — H₂ selectively scavenges the hydroxyl radicals that dominate radiation damage — but this is not a human study, and efficacy for ARS has not been demonstrated. It represents a scientifically motivated starting point for investigation. Any suggestion that H₂ „treats” radiation injury must wait for experimental and clinical validation.", "abstract": "Hydrogen is the most abundant chemical element in the universe, however, it is seldom regarded as a therapeutic gas. Recent studies show that inhaled hydrogen gas (H(2)) has antioxidant and antiapoptotic activities that protect the brain against ischemia-reperfusion injury and stroke by selectively reducing hydroxyl and peroxynitrite radicals. It is also well known that more than a half of the ionizing radiation-induced cellular damage is caused by hydroxyl radicals. Studies have show that reducing hydroxyl radicals can significantly improve the protection of cells from radiation damage. In like manner, we hypothesize that hydrogen therapy may be an effective, specific and unique treatment for acute radiation syndrome.", "conclusion": "Studies have show that reducing hydroxyl radicals can significantly improve the protection of cells from radiation damage. In like manner, we hypothesize that hydrogen therapy may be an effective, specific and unique treatment for acute radiation syndrome." }, { "pmid": "19505462", "year": 2009, "title": "Are the effects of alpha-glucosidase inhibitors on cardiovascular events related to elevated levels of hydrogen gas in the gastrointestinal tract?", "title_en": null, "title_de": "Stehen die Wirkungen von Alpha-Glucosidase-Hemmern auf kardiovaskuläre Ereignisse im Zusammenhang mit erhöhten Wasserstoffgasspiegeln im Magen-Darm-Trakt?", "journal": "FEBS letters", "authors": "Suzuki et al.", "author_search": "suzuki suzuki", "doi": "10.1016/j.febslet.2009.05.052", "doi_url": "https://doi.org/10.1016/j.febslet.2009.05.052", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/19505462/", "url": "https://h2medicine.org/studies/study-suzuki-2009-alpha-glucosidase-inhibitors-cardiovascular/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "cardiovascular", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2009 · Suzuki — Are the effects of alpha-glucosidase inhibitors on cardiovascular events related to elevated levels of hydrogen gas in the gastrointestinal tract?", "summary": "This theoretical paper proposes that the cardiovascular benefits of alpha-glucosidase inhibitors (such as acarbose) may partly be explained by increased H₂ production in the gut. When these diabetes drugs prevent carbohydrate digestion in the small intestine, colonic bacteria ferment the undigested sugars — producing H₂ gas. The authors suggest this endogenous H₂ might act as an antioxidant and reduce oxidative stress linked to cardiovascular disease. (FEBS Letters, 2009.)", "assessment": "This is a theory/hypothesis paper, not an experimental study. It offers a stimulating idea connecting gut microbiome H₂ production to cardiovascular health via an antioxidant mechanism — but presents no new experimental data. The connection between acarbose, H₂, and cardiovascular protection remains an unproven hypothesis. It is historically interesting as an early attempt to integrate endogenous H₂ into clinical pharmacology thinking. No human or animal experiments were performed; direct causality cannot be inferred from this paper alone.", "abstract": "The major side-effect of treatment with alpha-glucosidase inhibitors, flatulence, occurs when undigested carbohydrates are fermented by colonic bacteria, resulting in gas formation. We propose that the cardiovascular benefits of alpha-glucosidase inhibitors are partly attributable to their ability to neutralise oxidative stress via increased production of H(2) in the gastrointestinal tract. Acarbose, which is an alpha-glucosidase inhibitor, markedly increased H(2) production, with a weaker effect on methane production. Our hypothesis is based on our recent discovery that H(2) acts as a unique antioxidant, and that when inhaled or taken orally as H(2)-dissolved water it ameliorates ischaemia-reperfusion injury and atherosclerosis development.", "conclusion": "Acarbose, which is an alpha-glucosidase inhibitor, markedly increased H(2) production, with a weaker effect on methane production. Our hypothesis is based on our recent discovery that H(2) acts as a unique antioxidant, and that when inhaled or taken orally as H(2)-dissolved water it ameliorates ischaemia-reperfusion injury and atherosclerosis development." }, { "pmid": "19486890", "year": 2009, "title": "Hydrogen mediates suppression of colon inflammation induced by dextran sodium sulfate.", "title_en": null, "title_de": "Wasserstoff vermittelt die Unterdrückung der durch Dextran-Natriumsulfat induzierten Kolonentzündung.", "journal": "Biochemical and biophysical research communications", "authors": "Kajiya et al.", "author_search": "kajiya kajiya", "doi": "10.1016/j.bbrc.2009.05.117", "doi_url": "https://doi.org/10.1016/j.bbrc.2009.05.117", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/19486890/", "url": "https://h2medicine.org/studies/study-kajiya-2009-mediates-suppression-colon-inflammation/", "methods": [ "inhalation" ], "indications": [ "metabolic", "immune-system", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2009 · Kajiya — Hydrogen mediates suppression of colon inflammation induced by dextran sodium sulfate.", "summary": "In a mouse model of inflammatory bowel disease, adding molecular hydrogen (H₂) to drinking water significantly suppressed colon inflammation induced by dextran sodium sulfate (DSS). H₂ reduced weight loss, colitis scores, colon shortening, and pro-inflammatory cytokines (IL-12, TNF-α, IL-1β), and histologically reduced tissue destruction and macrophage infiltration. (Biochemical and Biophysical Research Communications, 2009.)", "assessment": "This is a preclinical animal study — results cannot be directly transferred to humans. The DSS mouse model is a reasonable proxy for aspects of ulcerative colitis, and the findings (cytokine reduction, tissue protection) are biologically coherent with H₂'s known antioxidant and anti-inflammatory properties. However, mouse studies routinely overestimate effects seen in humans, and IBD has complex immunological and environmental components that a single-agent intervention may not address. This paper is a useful early signal; clinical evidence in humans with IBD would be needed before any conclusions about therapeutic use.", "abstract": "By its antioxidant effect, molecular hydrogen gas (H2) was reported to protect organs from tissue damage induced by ischemia reperfusion. To evaluate its anti-inflammatory effects, we established a mouse model of human inflammatory bowel disease (IBD) by supplying mice with water containing (1) dextran sodium sulfate (DSS) (5%), (2) DSS (5%) and H2, or (3) H2 only ad libitum up to 7 days. At day-7, DSS-induced pathogenic outcomes including, loss of body weight, increase of colitis score, pathogenic shortening of colon length, elevated level of IL-12, TNF-alpha and IL-1beta in colon lesion, were significantly suppressed by the addition of H2 to DSS solution. Histological analysis also revealed that the DSS-mediated colonic tissue destruction accompanied by macrophage infiltration was remarkably suppressed by H2. Therefore, the present study indicated that H2 can prevent the development of DSS-induced colitis in mice.", "conclusion": "Histological analysis also revealed that the DSS-mediated colonic tissue destruction accompanied by macrophage infiltration was remarkably suppressed by H2. Therefore, the present study indicated that H2 can prevent the development of DSS-induced colitis in mice." }, { "pmid": "19377306", "year": 2009, "title": "A novel antibody fragment targeting HAb18G/CD147 with cytotoxicity and decreased immunogenicity.", "title_en": null, "title_de": "Ein neuartiges Antikörperfragment, das auf HAb18G/CD147 abzielt, mit Zytotoxizität und verringerter Immunogenität.", "journal": "Cancer biology & therapy", "authors": "Zhu et al.", "author_search": "zhu zhu", "doi": "10.4161/cbt.8.11.8531", "doi_url": "https://doi.org/10.4161/cbt.8.11.8531", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/19377306/", "url": "https://h2medicine.org/studies/study-zhu-2009-antibody-fragment-targeting-hab18g/", "methods": [ "unspecified" ], "indications": [ "liver", "cancer" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2009 · Zhu — A novel antibody fragment targeting HAb18G/CD147 with cytotoxicity and decreased immunogenicity.", "summary": "This in-vitro study describes the engineering of a humanized antibody fragment targeting CD147, a protein overexpressed on hepatocellular carcinoma cells, to reduce immunogenicity while maintaining cytotoxic activity. The resulting construct showed reduced reactivity with anti-mouse antibodies from patients while retaining binding affinity and the ability to mediate cancer cell killing. (Cancer Biology and Therapy, 2009.)", "assessment": "This paper has no meaningful relevance to therapeutic molecular hydrogen (H₂). The term „hydrogen“ in this study refers exclusively to hydrogen bonds in protein structural chemistry — a fundamentally different concept from dissolved H₂ gas as an antioxidant therapy. The study is a solid in-vitro antibody engineering paper in liver cancer research, but should not be cited as evidence for H₂ therapeutic effects. Its presence in an H₂ database appears to be a false-positive due to keyword overlap.", "abstract": "[(131)I]Metuximab injection (Licartin) was an efficient therapeutic anti-hepatocellular carcinoma (HCC) radioimmunological agent generated by labeling (131)I with the murine monoclonal antibody fragment HAb18-F(ab')(2) but human anti-mouse antibody (HAMA) response in some patients after administration limited its clinical use. To reduce the immunogenicity of murine antibody, we attempted to humanize HAb18 by variable domain resurfacing based on the three-dimensional structure of Fv fragment. Considering the surface accessibility of non-human like framework residues and the potential to form a molecular hydrogen bond within the context of the homology modeled Fv of HAb18, three residues in a single chain fragment of antibody variable region of HAb18 (HAb18scFv) were replaced by their human counterparts. We fabricated a humanized version of HAb18scFv, HAb18-huscFv, to the human IgG1Fc fragment to form (HAb18-huscFv)(2)-Fc. The reactivity of (HAb18-huscFv)(2)-Fc to the serum of patients with HAMA response was decreased while its specificity and similar binding activity (K(D) = 1.5 x 10(-9) M) were retained compared with its parental antibody. In addition, this antibody is an efficient mediator of antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). These results suggest (HAb18-huscFv)(2)-Fc could be a more efficient antibody fragment with less immunogenicity and additional cytotoxicity function.", "conclusion": "In addition, this antibody is an efficient mediator of antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). These results suggest (HAb18-huscFv)(2)-Fc could be a more efficient antibody fragment with less immunogenicity and additional cytotoxicity function." }, { "pmid": "19237201", "year": 2009, "title": "Organotin meclofenamic complexes: Synthesis, crystal structures and antiproliferative activity of the first complexes of meclofenamic acid - novel anti-tuberculosis agents.", "title_en": null, "title_de": "Organozinn-Meclofenaminsäure-Komplexe: Synthese, Kristallstrukturen und antiproliferative Aktivität der ersten Komplexe der Meclofenaminsäure – neuartige Antituberkulose-Wirkstoffe.", "journal": "Journal of inorganic biochemistry", "authors": "Kovala-Demertzi et al.", "author_search": "kovala-demertzi kovala-demertzi", "doi": "10.1016/j.jinorgbio.2009.01.014", "doi_url": "https://doi.org/10.1016/j.jinorgbio.2009.01.014", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/19237201/", "url": "https://h2medicine.org/studies/study-kovalademertzi-2009-organotin-meclofenamic-complexes-synthesis/", "methods": [ "unspecified" ], "indications": [ "cancer", "respiratory" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2009 · Kovala-Demertzi — Organotin meclofenamic complexes: Synthesis, crystal structures and antiproliferative activity of the first complexes of meclofenamic acid — novel anti-tuberculosis agents.", "summary": "This in-vitro chemistry study synthesized and characterized organotin complexes of meclofenamic acid and tested them against cancer cell lines and Mycobacterium tuberculosis. The triphenyltin complex showed strong cytotoxic activity against breast, bladder, and lung cancer cell lines, as well as promising anti-tuberculosis activity. (Journal of Inorganic Biochemistry, 2009.)", "assessment": "This paper has no relevance to therapeutic molecular hydrogen (H₂). All mentions of „hydrogen“ refer to hydrogen bonds in crystal structures — a basic structural chemistry concept entirely unrelated to dissolved H₂ gas. The study investigates organotin compounds as potential cancer and tuberculosis drugs. It is legitimate medicinal inorganic chemistry but should not appear in a database focused on molecular hydrogen therapy.", "abstract": "The complexes [Me(2)(Meclo)SnOSn(Meclo)Me(2)](2) (2) and [Ph(3)Sn(Meclo)] (3) where HMeclo is meclofenamic acid, N-(2,6-dichloro-m-tolylanthranilic acid)], have been prepared and structurally characterized by means of vibrational, (1)H and (13)C NMR spectroscopies. The crystal structure of complexes (2) and (3) have been determined by X-ray crystallography. Three distannoxane rings are present to the dimeric tetraorganodistannoxane of planar ladder arrangement of (2). The structure is centro symmetric and features a central rhombus Sn(2)O(2) unit two additional tin atoms linked at the oxygen atoms. Five- and six-coordinated tin centers are present in the dimer distannoxane. X-ray analysis of (3) revealed a penta-coordinated structure containing Ph(3)Sn coordinated to the chelated carboxylato group. The polar imino hydrogen atom participates in intra-molecular hydrogen bonds. Complexes (2) and (3) are self-assembled via pi-->pi, C-H-pi, stacking interactions and intra-molecular hydrogen bonds. Meclofenamic acid and [Ph(3)Sn(Meclo)] have been evaluated for antiproliferative activity in vitro against three human cancer cell lines: MCF-7 (human breast cancer cell line), T24 (bladder cancer cell line), A-549 (non-small cell lung carcinoma) and a mouse L-929 (a fibroblast-like cell line cloned from strain L). The [Ph(3)Sn(Meclo)] complex exhibited high cytotoxic activity against all the cancer cell lines. Meclofenamic and [Ph(3)Sn(Meclo)] were tested for anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv. The [Ph(3)Sn(Meclo)] complex was found to be a promising anti-mycobacterial lead compound, displaying high activity against M. tuberculosis H37Rv.", "conclusion": "The [Ph(3)Sn(Meclo)] complex was found to be a promising anti-mycobacterial lead compound, displaying high activity against M. tuberculosis H37Rv." }, { "pmid": "19202298", "year": 2009, "title": "Enhanced induction of mitochondrial damage and apoptosis in human leukemia HL-60 cells due to electrolyzed-reduced water and glutathione.", "title_en": null, "title_de": "Verstärkte Induktion mitochondrialer Schäden und Apoptose in menschlichen Leukämie-HL-60-Zellen durch elektrolysiert-reduziertes Wasser und Glutathion.", "journal": "Bioscience, biotechnology, and biochemistry", "authors": "Tsai et al.", "author_search": "tsai tsai", "doi": "10.1271/bbb.80413", "doi_url": "https://doi.org/10.1271/bbb.80413", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/19202298/", "url": "https://h2medicine.org/studies/study-tsai-2009-enhanced-induction-mitochondrial-damage/", "methods": [ "unspecified" ], "indications": [ "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2009 · Tsai — Enhanced induction of mitochondrial damage and apoptosis in human leukemia HL-60 cells due to electrolyzed-reduced water and glutathione.", "summary": "This in-vitro study found that electrolyzed-reduced water (ERW) combined with glutathione (GSH) enhanced apoptosis in human leukemia (HL-60) cells, while showing no cytotoxic effect in normal blood cells. The combination upregulated pro-apoptotic Bax and downregulated anti-apoptotic Bcl-2, suggesting a mitochondria-dependent cell death pathway. (Bioscience, Biotechnology, and Biochemistry, 2009.)", "assessment": "This is an in-vitro (cell culture) study — its findings cannot be extrapolated to humans or to cancer treatment. The observed selective toxicity of ERW+GSH toward leukemia cells in a dish is biologically interesting, but the HL-60 cell line is an immortalized lab model far removed from actual human leukemia. No animal experiments or clinical data support these findings. The study is a hypothesis-generating preclinical observation, not evidence for cancer therapy.", "abstract": "Electrolzyed-reduced water (ERW) is a higher pH and lower oxidation-reduction potential water. In the present study, we examined the enhanced effect of ERW in the apoptosis of leukemia cells (HL-60) induced by glutathione (GSH). An enhanced inhibitory effect on the viability of the HL-60 cells was observed after treatment with a combination of ERW with various concentrations of GSH, whereas no cytotoxic effect in normal peripheral blood mononuclear cells was observed. The results of apoptotic related protein indicated that the induction of HL-60 cell death was caused by the induction of apoptosis through upregulation of Bax and downregulation of Bcl-2. The results of further investigation showed a diminution of intracellular GSH levels in ERW, and combination with GSH groups. These results suggest that ERW is an antioxidant, and that ERW, in combination with GSH, has an enhanced apoptosis-inducing effect on HL-60 cells, which might be mediated through the mitochondria-dependent pathway.", "conclusion": "The results of further investigation showed a diminution of intracellular GSH levels in ERW, and combination with GSH groups. These results suggest that ERW is an antioxidant, and that ERW, in combination with GSH, has an enhanced apoptosis-inducing effect on HL-60 cells, which might be mediated through the mitochondria-dependent pathway." }, { "pmid": "19109480", "year": 2009, "title": "Oral abscess caused by Campylobacter rectus: case report and literature review.", "title_en": null, "title_de": "Oraler Abszess verursacht durch Campylobacter rectus: Fallbericht und Literaturübersicht.", "journal": "Journal of clinical microbiology", "authors": "Mahlen et al.", "author_search": "mahlen mahlen", "doi": "10.1128/jcm.01590-08", "doi_url": "https://doi.org/10.1128/jcm.01590-08", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/19109480/", "url": "https://h2medicine.org/studies/study-mahlen-2009-oral-abscess-caused-campylobacter/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "sports-exercise", "cancer", "oral-health" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2009 · Mahlen — Oral abscess caused by Campylobacter rectus: case report and literature review.", "summary": "This case report and literature review describes the first documented case of a palate abscess caused by Campylobacter rectus in a patient with gastroesophageal adenocarcinoma. The organism was cultured under anaerobic conditions without additional hydrogen gas in the atmosphere, which is notable because C. rectus typically requires H₂ or formate as an electron donor to grow. (Journal of Clinical Microbiology, 2009.)", "assessment": "This paper is a clinical microbiology case report and literature review. Its connection to molecular H₂ is indirect — it concerns a bacterium that can metabolize H₂ as a growth substrate, not H₂ as a therapeutic agent. The study provides no evidence about therapeutic hydrogen use in humans. It is not a source for claims about H₂ health effects. For completeness: the patient had a rare non-periodontal oral abscess with an unusual oral pathogen.", "abstract": "Campylobacter rectus was isolated under routine anaerobic conditions (no additional hydrogen gas in the atmosphere) from an oral, nonperiodontal abscess from a patient with gastroesophageal adenocarcinoma. We report the first case of a palate abscess caused by C. rectus and review the literature and atmospheric requirements of this organism.", "conclusion": "We report the first case of a palate abscess caused by C. rectus and review the literature and atmospheric requirements of this organism." }, { "pmid": "18508354", "year": 2009, "title": "The mechanism of deposition of calcium phosphate coatings from solution onto magnesium alloy AZ31.", "title_en": null, "title_de": "Der Mechanismus der Abscheidung von Calciumphosphat-Beschichtungen aus Lösung auf der Magnesiumlegierung AZ31.", "journal": "Journal of biomedical materials research. Part A", "authors": "Gray-Munro et al.", "author_search": "gray-munro gray-munro", "doi": "10.1002/jbm.a.32107", "doi_url": "https://doi.org/10.1002/jbm.a.32107", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/18508354/", "url": "https://h2medicine.org/studies/study-graymunro-2009-mechanism-deposition-calcium-phosphate/", "methods": [ "inhalation" ], "indications": [ "sports-exercise" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2009 · Gray-Munro — The mechanism of deposition of calcium phosphate coatings from solution onto magnesium alloy AZ31.", "summary": "This in-vitro materials science study investigated how calcium phosphate coatings can be deposited onto magnesium alloy surfaces to slow their degradation in biological environments. Magnesium alloys are of interest as bioabsorbable implant materials, but their rapid corrosion produces hydrogen gas as a byproduct — a problem this coating approach aims to address. (Journal of Biomedical Materials Research, 2009.)", "assessment": "This paper has no relevance to therapeutic molecular hydrogen (H₂). Hydrogen gas appears only as an unwanted corrosion byproduct that the study seeks to suppress. The work is relevant to bioabsorbable orthopaedic implant engineering, not to hydrogen therapy.", "abstract": "In recent years, magnesium alloys have been proposed as a new class of metallic bioabsorbable implant material. Unfortunately, hydrogen gas evolution and an increase in alkalinity are both byproducts of the degradation process. This necessitates the development of magnesium alloys with controlled degradation rates. The development of biocompatible coatings that can delay the onset of corrosion is essential for improving the lifetime and performance of these materials in vivo. Calcium phosphate coatings have been shown to improve the biocompatibility of metallic implants for orthopedic applications. In this article, we report a solution chemistry technique for depositing calcium phosphate coatings on magnesium alloy surfaces. Our kinetic studies indicate that the deposition of the coating is related to the anodic dissolution of the substrate. Characterization of the coating by XPS, SEM/EDS, and XRD reveal that the coating produced is a poorly crystalline calcium magnesium hydroxyapatite material.", "conclusion": "Our kinetic studies indicate that the deposition of the coating is related to the anodic dissolution of the substrate. Characterization of the coating by XPS, SEM/EDS, and XRD reveal that the coating produced is a poorly crystalline calcium magnesium hydroxyapatite material." }, { "pmid": "19083400", "year": 2008, "title": "Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance", "title_en": null, "title_de": "Supplementierung mit wasserstoffreichem Wasser verbessert den Fett- und Glukosestoffwechsel bei Patienten mit Typ-2-Diabetes oder gestörter Glukosetoleranz", "journal": "Nutrition Research", "authors": "Kajiyama et al.", "author_search": "kajiyama kajiyama", "doi": "10.1016/j.nutres.2008.01.008", "doi_url": "https://doi.org/10.1016/j.nutres.2008.01.008", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/19083400/", "url": "https://h2medicine.org/studies/study-kajiyama-2008-hydrogen-rich-water-type-2-diabetes-glucose-metabolism/", "methods": [ "drinking-hrw" ], "indications": [ "diabetes", "metabolic", "cardiovascular" ], "evidence_level": 3, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2008 · Kajiyama — Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance", "summary": "Hydrogen-rich water lowers oxidative stress in diabetics. In a randomized double-blind crossover (36 patients, 900 ml/day, 8 weeks), harmfully modified LDL cholesterol fell by 15.5 %; in 4 of 6 prediabetics the glucose tolerance test normalized. (Nutrition Research, 2008 — one of the first clinical H₂ studies with a rigorous design.)", "assessment": "Directly relevant to glucose and lipid metabolism in type-2 diabetes and a strong piece of evidence, because the study design (double-blind, placebo-controlled, crossover) largely rules out chance and placebo effects. The study translates the mechanism of Ohsawa 2007 for the first time into measurable clinical benefit in a common disease. Limitation, stated honestly: small sample (n=36), surrogate markers instead of hard endpoints (no statement on downstream disease), and 8 weeks is short.", "abstract": "Oxidative stress is recognized widely as being associated with various disorders including diabetes, hypertension, and atherosclerosis. It is well established that hydrogen has a reducing action. We therefore investigated the effects of hydrogen-rich water intake on lipid and glucose metabolism in patients with either type 2 diabetes mellitus (T2DM) or impaired glucose tolerance (IGT). We performed a randomized, double-blind, placebo-controlled, crossover study in 30 patients with T2DM controlled by diet and exercise therapy and 6 patients with IGT. The patients consumed either 900 mL/d of hydrogen-rich pure water or 900 mL of placebo pure water for 8 weeks, with a 12-week washout period. Several biomarkers of oxidative stress, insulin resistance, and glucose metabolism, assessed by an oral glucose tolerance test, were evaluated at baseline and at 8 weeks. Intake of hydrogen-rich water was associated with significant decreases in the levels of modified low-density lipoprotein (LDL) cholesterol (ie, modifications that increase the net negative charge of LDL), small dense LDL, and urinary 8-isoprostanes by 15.5% (P < .01), 5.7% (P < .05), and 6.6% (P < .05), respectively. Hydrogen-rich water intake was also associated with a trend of decreased serum concentrations of oxidized LDL and free fatty acids, and increased plasma levels of adiponectin and extracellular-superoxide dismutase. In 4 of 6 patients with IGT, intake of hydrogen-rich water normalized the oral glucose tolerance test. In conclusion, these results suggest that supplementation with hydrogen-rich water may have a beneficial role in prevention of T2DM and insulin resistance.", "conclusion": "In 4 of 6 patients with IGT, intake of hydrogen-rich water normalized the oral glucose tolerance test. In conclusion, these results suggest that supplementation with hydrogen-rich water may have a beneficial role in prevention of T2DM and insulin resistance." }, { "pmid": "19102360", "year": 2008, "title": "Extensive atrophic gastritis linked to increased levels of intraluminal hydrogen gas.", "title_en": null, "title_de": "Ausgedehnte atrophische Gastritis in Verbindung mit erhöhten Spiegeln von intraluminalem Wasserstoffgas", "journal": "Hepato-gastroenterology", "authors": "Urita et al.", "author_search": "urita urita", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/19102360/", "url": "https://h2medicine.org/studies/study-urita-2008-extensive-atrophic-gastritis-linked/", "methods": [], "indications": [ "other" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "breath-test", "headline": "2008 · Urita et al. — Extensive Atrophic Gastritis Linked to Increased Levels of Intraluminal Hydrogen Gas", "summary": "This gastroenterology study measures hydrogen gas produced naturally by gut bacteria in 647 patients undergoing upper endoscopy — it is not an H₂ therapy study. The finding is that intraduodenal H₂ levels rise with the progression of atrophic gastritis, suggesting a link between gastric acid deficiency, bacterial overgrowth, and endogenous H₂ production. (Hepato-Gastroenterology, 2008.)", "assessment": "Off-topic for H₂ therapy. This study investigates endogenous intraluminal hydrogen gas produced by gut bacteria — not therapeutic molecular hydrogen. No H₂ was administered. The study contributes to gastroenterology knowledge about the relationship between gastric acid, bacterial overgrowth, and microbiome-derived H₂. It is not evidence for or against H₂ therapeutic effects.", "abstract": "BACKGROUND/AIMS: Gastric acid plays an important part in the prevention of bacterial colonization of the gastrointestinal tract. If these bacteria have an ability of hydrogen (H2) fermentation, intraluminal H2 gas might be detected. We attempted to measure the intraluminal H2 concentrations to determine the bacterial overgrowth in the gastrointestinal tract. METHODOLOGY: Studies were performed in 647 consecutive patients undergoing upper endoscopy. At the time of endoscopic examination, we intubated the stomach and the descending part of the duodenum without inflation by air, and 20 ml of intraluminal gas samples of both sites was collected through the biopsy channel. Intraluminal H2 concentrations were measured by gas chromatography. RESULTS: Over all, intragastric and intraduodenal H2 gas was detected in 566 (87.5%) and 524 (81.0%), respectively. The mean values of intragastric and intraduodenal H2 gas were 8.5 +/- 15.9 and 13.2 +/- 58.0 ppm, respectively. The intraduodenal H2 level was increased with the progression of atrophic gastritis, whereas the intragastric H2 level was the highest in patients without atrophic gastritis. CONCLUSIONS: The intraduodenal hydrogen levels were increased with the progression of atrophic gastritis. It is likely that the influence of hypochlorhydria on bacterial overgrowth in the proximal small intestine is more pronounced, compared to that in the stomach.", "conclusion": "The intraduodenal hydrogen levels were increased with the progression of atrophic gastritis. It is likely that the influence of hypochlorhydria on bacterial overgrowth in the proximal small intestine is more pronounced, compared to that in the stomach." }, { "pmid": "18473836", "year": 2008, "title": "The hydrogenosome as a drug target.", "title_en": null, "title_de": "Das Hydrogenosom als Wirkstoffziel.", "journal": "Current pharmaceutical design", "authors": "Benchimol", "author_search": "benchimol benchimol", "doi": "10.2174/138161208784041114", "doi_url": "https://doi.org/10.2174/138161208784041114", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/18473836/", "url": "https://h2medicine.org/studies/study-benchimol-2008-hydrogenosome-drug-target/", "methods": [ "unspecified" ], "indications": [ "cardiovascular", "respiratory", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2008 · Benchimol — The hydrogenosome as a drug target.", "summary": "This in-vitro review/study describes hydrogenosomes — organelles found in certain parasitic microorganisms (such as Trichomonas) that produce molecular hydrogen — as potential drug targets for anti-parasitic therapies. Because hydrogenosome metabolism differs fundamentally from human mitochondria, drugs targeting them could selectively kill parasites without harming the host. (Current Pharmaceutical Design, 2008.)", "assessment": "This paper is not relevant to therapeutic H₂ use in humans. The H₂ connection is purely metabolic — hydrogenosomes produce H₂ as a byproduct of anaerobic energy metabolism. This is a different biological context entirely from therapeutic molecular H₂ as an antioxidant. The study is solid parasitology/drug target research. It should not be cited as evidence for H₂ health effects.", "abstract": "Hydrogenosomes are spherical or slightly elongated organelles found in non-mitochondrial organisms. In Trichomonas hydrogenosomes measure between 200 to 500 nm, but under drug treatment they can reach 2 microm. Like mitochondria hydrogenosomes: (1) are surrounded by two closely apposed membranes and present a granular matrix: (2) divide in three different ways: segmentation, partition and the heart form; (3) they may divide at any phase of the cell cycle; (4) produce ATP; (5) participate in the metabolism of pyruvate formed during glycolysis; (6) are the site of molecular hydrogen formation; (7) present a relationship with the endoplasmic reticulum; (8) incorporate calcium; (9) import proteins post-translationally; (10) present cardiolipin. However, there are differences, such as: (1) absence of genetic material, at least in trichomonas; (2) lack a respiratory chain and cytochromes; (3) absence of the F(0)-F(1) ATPase; (4) absence of the tricarboxylic acid cycle; (5) lack of oxidative phosphorylation; (6) presence of peripheral vesicles. Hydrogenosomes are considered an excellent drug target since their metabolic pathway is distinct from those found in mitochondria and thus medicines directed to these organelles will probably not affect the host-cell. The main drug used against trichomonads is metronidazole, although other drugs such as beta-Lapachone, colchicine, Taxol, nocodazole, griseofulvin, cytochalasins, hydroxyurea, among others, have been used in trichomonad studies, showing: (1) flagella internalization forming pseudocyst; (2) dysfunctional hydrogenosomes; (3) hydrogenosomes with abnormal sizes and shapes and with an electron dense deposit called nucleoid; (4) intense autophagy in which hydrogenosomes are removed and further digested in lysosomes.", "conclusion": "Hydrogenosomes are considered an excellent drug target since their metabolic pathway is distinct from those found in mitochondria and thus medicines directed to these organelles will probably not affect the host-cell. The main drug used against trichomonads is metronidazole, although other drugs such as beta-Lapachone, colchicine, Taxol, nocodazole, griseofulvin, cytochalasins, hydroxyurea, among " }, { "pmid": "18270200", "year": 2008, "title": "A role for IOP1 in mammalian cytosolic iron-sulfur protein biogenesis.", "title_en": null, "title_de": "Eine Rolle von IOP1 in der Biogenese zytosolischer Eisen-Schwefel-Proteine bei Säugetieren.", "journal": "The Journal of biological chemistry", "authors": "Song et al.", "author_search": "song song", "doi": "10.1074/jbc.m708077200", "doi_url": "https://doi.org/10.1074/jbc.m708077200", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/18270200/", "url": "https://h2medicine.org/studies/study-song-2008-iop1-mammalian-cytosolic-iron/", "methods": [ "inhalation" ], "indications": [ "sports-exercise", "neurology" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2008 · Song — A role for IOP1 in mammalian cytosolic iron-sulfur protein biogenesis.", "summary": "This in-vitro cell study identified IOP1 — a mammalian protein homologous to bacterial iron-only hydrogenases — as essential for the maturation of cytosolic iron-sulfur (Fe-S) proteins in human cells. Reducing IOP1 levels impaired cytosolic aconitase and xanthine oxidase activity, revealing a eukaryotic pathway for Fe-S cluster assembly outside mitochondria. (The Journal of Biological Chemistry, 2008.)", "assessment": "This paper is not relevant to therapeutic molecular hydrogen (H₂). It investigates a mammalian protein that is evolutionarily related to bacterial hydrogenases but performs a completely different function (Fe-S cluster assembly). The study is valuable fundamental biochemistry about iron metabolism, but does not bear on H₂ therapy in any way.", "abstract": "The biogenesis of cytosolic iron-sulfur (Fe-S) proteins in mammalian cells is poorly understood. In Saccharomyces cerevisiae, there is a pathway dedicated to cytosolic Fe-S protein maturation that involves several essential proteins. One of these is Nar1, which intriguingly is homologous to iron-only hydrogenases, ancient enzymes that catalyze the formation of hydrogen gas in anaerobic bacteria. There are two orthologues of Nar1 in mammalian cells, iron-only hydrogenase-like protein 1 (IOP1) and IOP2 (also known as nuclear prelamin A recognition factor). We examined IOP1 for a potential role in mammalian cytosolic Fe-S protein biogenesis. We found that knockdown of IOP1 in both HeLa and Hep3B cells decreases the activity of cytosolic aconitase, an Fe-S protein, but not that of mitochondrial aconitase. Knockdown of IOP2, in contrast, had no effect on either. The decrease in aconitase activity upon IOP1 knockdown is rescued by expression of a small interference RNA-resistant version of IOP1. Upon loss of its Fe-S cluster, cytosolic aconitase is known to be converted to iron regulatory protein 1, and consistent with this, we found that IOP1 knockdown increases transferrin receptor 1 mRNA levels and decreases ferritin heavy chain protein levels. IOP1 knockdown also leads to a decrease in activity of xanthine oxidase, a distinct cytosolic Fe-S protein. Taken together, these results provide evidence that IOP1 is involved in mammalian cytosolic Fe-S protein maturation.", "conclusion": "IOP1 knockdown also leads to a decrease in activity of xanthine oxidase, a distinct cytosolic Fe-S protein. Taken together, these results provide evidence that IOP1 is involved in mammalian cytosolic Fe-S protein maturation." }, { "pmid": "18175936", "year": 2008, "title": "Inhibitory effect of electrolyzed reduced water on tumor angiogenesis.", "title_en": null, "title_de": "Hemmende Wirkung von elektrolysiert-reduziertem Wasser auf die Tumorangiogenese.", "journal": "Biological & pharmaceutical bulletin", "authors": "Ye et al.", "author_search": "ye ye", "doi": "10.1248/bpb.31.19", "doi_url": "https://doi.org/10.1248/bpb.31.19", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/18175936/", "url": "https://h2medicine.org/studies/study-ye-2008-inhibitory-electrolyzed-reduced-tumor/", "methods": [ "drinking-hrw" ], "indications": [ "cardiovascular", "cancer", "respiratory", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2008 · Ye — Inhibitory effect of electrolyzed reduced water on tumor angiogenesis.", "summary": "This in-vitro study found that electrolyzed reduced water (ERW) reduced VEGF (vascular endothelial growth factor) gene expression and protein secretion in a human lung adenocarcinoma cell line, and inhibited in vitro formation of vascular tubules. ERW scavenged intracellular hydrogen peroxide and suppressed the ERK signaling pathway, which regulates VEGF expression. (Biological and Pharmaceutical Bulletin, 2008.)", "assessment": "This is an in-vitro (cell culture) study. The anti-angiogenic findings are mechanistically plausible and internally consistent, but cannot be extrapolated to cancer treatment in humans. Cell culture experiments with cancer lines routinely overestimate therapeutic effects. The critical question — whether ERW/H₂ can reduce tumor angiogenesis in a living organism at therapeutic concentrations — remains unanswered. The study is a useful preclinical signal warranting further investigation.", "abstract": "Vascular endothelial growth factor (VEGF) is a key mediator of tumor angiogenesis. Tumor cells are exposed to higher oxidative stress compared to normal cells. Numerous reports have demonstrated that the intracellular redox (oxidation/reduction) state is closely associated with the pattern of VEGF expression. Electrolyzed reduced water (ERW) produced near the cathode during the electrolysis of water scavenged intracellular H(2)O(2) and decreased the release of H(2)O(2) from a human lung adenocarcinoma cell line, A549, and down-regulated both VEGF transcription and protein secretion in a time-dependent manner. To investigate the signal transduction pathway involved in regulating VEGF expression, mitogen-activated kinase (MAPK) specific inhibitors, SB203580 (p38 MAPK inhibitor), PD98059 (ERK1/2 inhibitor) and JNKi (c-Jun N-terminal protein kinase inhibitor) were applied. The results showed that only PD98059 blocks VEGF expression, suggesting an important role for ERK1/2 in regulating VEGF expression in A549 cells. As well, ERW inhibited the activation of extracellular signal-regulated kinase (ERK) in a time-dependent manner. Co-culture experiments to analyze in vitro tubule formation assay revealed that A549 cell-derived conditioned medium significantly stimulated the formation of vascular tubules in all analyzed parameters; tubule total area, tubule junction, number of tubules, and total tubule length. ERW counteracted the effect of A549 cell-conditioned medium and decreased total tube length (p<0.01). The present study demonstrated that ERW down-regulated VEGF gene transcription and protein secretion through inactivation of ERK.", "conclusion": "ERW counteracted the effect of A549 cell-conditioned medium and decreased total tube length (p<0.01). The present study demonstrated that ERW down-regulated VEGF gene transcription and protein secretion through inactivation of ERK." }, { "pmid": "18066702", "year": 2008, "title": "Hydrogen as an energy source for the human pathogen Bilophila wadsworthia.", "title_en": null, "title_de": "Wasserstoff als Energiequelle für den humanpathogenen Erreger Bilophila wadsworthia.", "journal": "Antonie van Leeuwenhoek", "authors": "da Silva et al.", "author_search": "da silva da silva", "doi": "10.1007/s10482-007-9215-x", "doi_url": "https://doi.org/10.1007/s10482-007-9215-x", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/18066702/", "url": "https://h2medicine.org/studies/study-dasilva-2008-energy-source-pathogen-bilophila/", "methods": [ "unspecified" ], "indications": [ "sports-exercise" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2008 · da Silva — Hydrogen as an energy source for the human pathogen Bilophila wadsworthia.", "summary": "This in-vitro microbiology study showed that the gut pathogen Bilophila wadsworthia can use molecular hydrogen (H₂) as an excellent growth substrate through its multiple hydrogenase enzymes. The organism — the third most common isolate in perforated appendicitis — can express up to five different hydrogenases and oxidize H₂ for energy. (Antonie van Leeuwenhoek, 2008.)", "assessment": "This paper is not relevant to therapeutic molecular hydrogen (H₂). It concerns the metabolic use of H₂ by a gut pathogen as an energy source. The study is solid microbiology on Bilophila wadsworthia, but it does not support claims about H₂ health benefits in humans. If anything, it raises a nuanced counterpoint: some anaerobic gut pathogens thrive on H₂, which is relevant context when evaluating strategies to increase gut H₂ production.", "abstract": "The gram-negative anaerobic gut bacterium Bilophila wadsworthia is the third most common isolate in perforated and gangrenous appendicitis, being also found in a variety of other infections. This organism performs a unique kind of anaerobic respiration in which taurine, a major organic solute in mammals, is used as a source of sulphite that serves as terminal acceptor for the electron transport chain. We show here that molecular hydrogen, one of the major products of fermentative bacteria in the colon, is an excellent growth substrate for B. wadsworthia. We have quantified the enzymatic activities associated with the oxidation of H(2), formate and pyruvate for cells obtained in different growth conditions. The cell extracts present high levels of hydrogenase activity, and up to five different hydrogenases can be expressed by this organism. One of the hydrogenases appears to be constitutive, whereas the others show differential expression in different growth conditions. Two of the hydrogenases are soluble and are recognised by antibodies against a [FeFe] hydrogenase of a sulphate reducing bacterium. One of these hydrogenases is specifically induced during fermentative growth on pyruvate. Another two hydrogenases are membrane-bound and show increased expression in cells grown with hydrogen. Further work should be carried out to reveal whether oxidation of hydrogen contributes to the virulence of B. wadsworthia.", "conclusion": "Further work should be carried out to reveal whether oxidation of hydrogen contributes to the virulence of B. wadsworthia." }, { "pmid": "17853416", "year": 2008, "title": "Preliminary tribological evaluation of nanostructured diamond coatings against ultra-high molecular weight polyethylene.", "title_en": null, "title_de": "Vorläufige tribologische Bewertung nanostrukturierter Diamantbeschichtungen gegen ultrahochmolekulares Polyethylen.", "journal": "Journal of biomedical materials research. Part B, Applied biomaterials", "authors": "Hill et al.", "author_search": "hill hill", "doi": "10.1002/jbm.b.30926", "doi_url": "https://doi.org/10.1002/jbm.b.30926", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/17853416/", "url": "https://h2medicine.org/studies/study-hill-2008-preliminary-tribological-nanostructured-diamond/", "methods": [ "inhalation" ], "indications": [ "joints-rheumatology" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2008 · Hill — Preliminary tribological evaluation of nanostructured diamond coatings against ultra-high molecular weight polyethylene.", "summary": "This in-vitro materials science study evaluated nanostructured diamond (NSD) coatings on titanium alloy as a potential counterface for polyethylene in joint replacement implants. Hydrogen-rich and helium-rich feedgas mixtures were used in the deposition process. Wear factors were comparable to cobalt-chromium alloy, suggesting NSD could be a viable alternative implant material. (Journal of Biomedical Materials Research B, 2008.)", "assessment": "This paper has no relevance to therapeutic molecular hydrogen (H₂). Hydrogen gas appears only as a component of the industrial CVD process used to fabricate the diamond coatings. The study is solid orthopaedic biomaterials engineering. Its inclusion in an H₂ therapy database is a false positive due to process-chemistry keyword overlap.", "abstract": "BACKGROUND: Some loss of joint prostheses has been attributed to osteolytic loosening associated with debris from wear of polyethylene articulating against metal alloys. Reduced polyethylene wear has been reported with ceramics serving as an alternative counterface. METHODS: Nanostructured Diamond (NSD) coatings were deposited onto Ti6Al4V by microwave plasma-assisted chemical vapor deposition, with both hydrogen-rich (H-NSD) and helium-rich (He-NSD) feedgas mixtures. Pin-on-disk wear tests of polyethylene against NSD and CoCr were performed in serum lubrication at body temperature. Scanning electron microscopy was used to examine surface morphology, and nanoindentation was used to determine hardness and modulus of the polyethylene wear surfaces. Raman spectroscopy, surface roughness, and wettability analyses of the NSD coatings were performed. RESULTS: Raman spectroscopy confirmed sp(2) and sp(3) bonded carbon in the NSD coatings. No significant differences in wear factors were found between polyethylene on H-NSD, He-NSD, and CoCr, despite higher roughness and friction coefficients for the He-NSD and H-NSD coatings, compared with CoCr. Contact angles for the diamond coatings were reduced following the wear tests, indicating that these surfaces became more hydrophilic. Numerous small protuberances were observed on pins articulated against CoCr, and a single, large protuberance was observed in polyethylene-on-NSD. These features were conjectured to be reconsolidated polyethylene particles. Nanoindentation modulus and hardness of the worn polyethylene surfaces were lower for polyethylene-on-diamond than for polyethylene-on-CoCr. CONCLUSIONS: As a counterface to polyethylene, NSD-coated Ti6Al4V produced wear factors comparable to CoCr in the present pin-on-disk tests, a promising step towards its use in joint replacement bearing applications.", "conclusion": "As a counterface to polyethylene, NSD-coated Ti6Al4V produced wear factors comparable to CoCr in the present pin-on-disk tests, a promising step towards its use in joint replacement bearing applications." }, { "pmid": "17683943", "year": 2008, "title": "Practical experiences with the synthesis of [11C]CH3I through gas phase iodination reaction using a TRACERlabFXC synthesis module.", "title_en": null, "title_de": "Praktische Erfahrungen mit der Synthese von [¹¹C]CH₃I durch eine Gasphasen-Iodierungsreaktion unter Verwendung eines TRACERlabFXC-Synthesemoduls", "journal": "Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine", "authors": "Kniess et al.", "author_search": "kniess kniess", "doi": "10.1016/j.apradiso.2007.06.005", "doi_url": "https://doi.org/10.1016/j.apradiso.2007.06.005", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/17683943/", "url": "https://h2medicine.org/studies/study-kniess-2008-practical-experiences-synthesis-11c/", "methods": [ "inhalation" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2008 · Kniess et al. — Practical experiences with the synthesis of [¹¹C]CH₃I through gas phase iodination using a TRACERlabFXC synthesis module", "summary": "This in-vitro chemistry study optimises the synthesis of the radiotracer [¹¹C]CH₃I — a carbon-11-labelled compound used in PET imaging — by testing several nickel catalysts for the intermediate hydrogen-reduction step. Nanosize nickel proved superior, achieving the best yields. The study has no direct relevance to molecular hydrogen as a health or therapeutic agent.", "assessment": "This is a technical radiochemistry paper with no bearing on molecular hydrogen as a dietary supplement, antioxidant, or therapeutic agent. H₂ appears only as an industrial reductant in a radiopharmaceutical synthesis workflow. The study is methodologically sound within its domain, but it is not a biological H₂ study and provides no evidence — positive or negative — regarding H₂ health effects.", "abstract": "The results of [(11)C]CH(3)I synthesis through hydrogen gas reduction of [(11)C]CO(2) on different nickel catalysts (HARSHAW-nickel, SHIMALITE-nickel, nickel on silica/alumina, nickel nanosize 99.99%) followed by gas phase iodination using a TRACERlab FX(C) synthesis unit are reported. Further reaction parameters such as furnace temperatures, flow rate of hydrogen gas and reduction time were optimized. It was found that reduction of [(11)C]CO(2) proceeded in 28-83% yield depending on the nickel catalyst and temperature. The gas phase iodination (methane conversion) gave 31-62% of [(11)C]CH(3)I depending on temperature and amount of iodine in the iodine furnace. [(11)C]CH(3)I was used for heteroatom methylation reactions exemplified by a piperazine and a phenol (1 and 3). The specific activity of the (11)C-labelled products 2 and 4 was determined after HPLC purification and solid-phase extraction. Compounds 2 and 4 were obtained in 8-14% radiochemical yield (decay-corrected, based upon trapped [(11)C]CH(4)) within 30 min. The specific activity was determined to be in the range of 20-30 GBq/mumol at the end-of-synthesis. Nickel catalyst nanosize was found to be superior compared with other Ni catalysts tested. The relatively low specific activity may be mainly due to carbon contaminations originating from the long copper tubing (500 m) between the cyclotron and the radiochemistry facility.", "conclusion": "Nickel catalyst nanosize was found to be superior compared with other Ni catalysts tested. The relatively low specific activity may be mainly due to carbon contaminations originating from the long copper tubing (500 m) between the cyclotron and the radiochemistry facility." }, { "pmid": "17951687", "year": 2007, "title": "A mitosome purification protocol based on percoll density gradients and its use in validating the mitosomal nature of Entamoeba histolytica mitochondrial Hsp70.", "title_en": null, "title_de": "Ein Mitosom-Aufreinigungsprotokoll auf Basis von Percoll-Dichtegradienten und seine Verwendung zur Validierung der mitosomalen Natur des mitochondrialen Hsp70 von Entamoeba histolytica", "journal": "Methods in molecular biology (Clifton, N.J.)", "authors": "Tovar et al.", "author_search": "tovar tovar", "doi": "10.1007/978-1-59745-466-7_11", "doi_url": "https://doi.org/10.1007/978-1-59745-466-7_11", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/17951687/", "url": "https://h2medicine.org/studies/study-tovar-2007-mitosome-purification-protocol-percoll/", "methods": [ "unspecified" ], "indications": [ "sports-exercise" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2007 · Tovar et al. — A mitosome purification protocol based on percoll density gradients and its use in validating the mitosomal nature of Entamoeba histolytica mitochondrial Hsp70", "summary": "This cell biology study describes a method to isolate „mitosomes“ — highly reduced, hydrogen-independent remnants of mitochondria — from the intestinal parasite Entamoeba histolytica. The paper confirms that a key chaperone protein (Hsp70) resides in these organelles. Molecular hydrogen (H₂) is mentioned only in passing as a criterion that distinguishes mitosomes from hydrogenosomes; there is no therapeutic or health context.", "assessment": "This is a cell biology / parasitology methods paper with no relevance to H₂ as a health intervention. The sole mention of molecular hydrogen is definitional — to distinguish mitosome from hydrogenosome. The study is methodologically rigorous within its domain. It does not provide any evidence regarding H₂ supplementation or biological H₂ effects in humans or mammals.", "abstract": "Mitochondria are indispensable for aerobic respiration, but many microbial eukaryotes have lost this function through reductive evolution. Their modified mitochondria are known as hydrogenosomes or mitosomes depending on whether or not they produce molecular hydrogen. The intestinal parasite Entamoeba histolytica contains mitosomes whose role in cellular metabolism is unclear. Only three proteins have been shown thus far to reside in these organelles: the molecular chaperones Hsp10 and Hsp60 and an unusual ADP/ATP carrier. Here we describe the isolation of E. histolytica mitosomes by cellular fractionation and density gradient centrifugation and show that the mitochondrial-type chaperone Hsp70 is also housed in Entamoeba mitosomes.", "conclusion": "Here we describe the isolation of E. histolytica mitosomes by cellular fractionation and density gradient centrifugation and show that the mitochondrial-type chaperone Hsp70 is also housed in Entamoeba mitosomes." }, { "pmid": "17926473", "year": 2007, "title": "[Blood flow and morphofunctional status of gastroduodenal mucosa in different phases of peptic ulcer].", "title_en": null, "title_de": "Blutfluss und morphofunktioneller Status der gastroduodenalen Schleimhaut in verschiedenen Phasen des peptischen Ulkus", "journal": "Terapevticheskii arkhiv", "authors": "Maev et al.", "author_search": "maev maev", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/17926473/", "url": "https://h2medicine.org/studies/study-maev-2007-blood-flow-morphofunctional-status/", "methods": [], "indications": [ "immune-system" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "tracer-clearance", "headline": "2007 · Maev et al. — Blood Flow and Morphofunctional Status of Gastroduodenal Mucosa in Different Phases of Peptic Ulcer", "summary": "This gastroenterology study uses the hydrogen gas clearance technique to measure gastric and duodenal mucosal blood flow in peptic ulcer disease — it is not an H₂ therapy study. H₂ gas is used here as a physiological measurement tracer, not as a therapeutic agent. The study focuses on how Helicobacter pylori infection and mucosal inflammation affect blood flow during ulcer healing and relapse. (Terapevticheskii arkhiv, 2007.)", "assessment": "Off-topic for H₂ therapy. The hydrogen gas clearance technique is used here exclusively as a blood-flow measurement tool. No H₂ therapeutic intervention was applied to patients. This peptic ulcer study belongs to gastroenterology and clinical physiology research, not to molecular hydrogen medicine. The indication tags in the source metadata (immune-system) appear to be a classification error.", "abstract": "AIM: To investigate gastric and duodenal mucosal blood flow (MBF) in different phases of gastric ulcer (GU) and duodenal ulcer (DU) and its relation both to Helicobacter pylori (HP) infection and mucosal disorders. MATERIAL AND METHODS: Upper endoscopy and histological examinations (score of inflammation, atrophy, metaplasy) were performed in 407 patients with DU and 103 with GU. Gastric and duodenal MBF were assessed by the hydrogen gas clearance technique in 102 DU and 95 GU patients. HP was detected by histology. Gastric secretion was measured in the interdigestive period and after stimulation by pentagastrin. RESULTS: Lowering of MBF in gastric antrum and duodenum was observed in DU and GU patients only with score 3 of HP infection. DU healing is accompanied with a decrease of HP value and improvement of mucosal histology. At the same time MBF exhibits a significant rise: in the duodenum (by 45%) at the stage of white scar; in gastric antrum (by 26%) and body (by 40%) at healing stage, but a decrease in white scar. During healing of GU gastric MBF reached maximum in active ulcer but in white scar MBF was significantly lower. MBF at ulcer margin and MBF in ulcer crater was the same (30 ml/min/100 g) with MBF in the region of white scar with enhanced inflammation (score 2.1) before GU relapse. CONCLUSION: Changes of MBF in different phases of ulcer are, in part, determined both by HP and by mucosal morphological disorders. The ratio MBF increase in ulcer healing/MBF reduction in ulcer relapse is the same (30% from optimal) and it is restitution entity. The MBF level of 30 ml/min/100 g was assessed as crucial in ulcerogenesis. Lowering MBF in mucosa with remaining inflammation in the scar region may predict GU relapse.", "conclusion": "Changes of MBF in different phases of ulcer are, in part, determined both by HP and by mucosal morphological disorders. The ratio MBF increase in ulcer healing/MBF reduction in ulcer relapse is the same (30% from optimal) and it is restitution entity. The MBF level of 30 ml/min/100 g was assessed as crucial in ulcerogenesis. Lowering MBF in mucosa with remaining inflammation in the scar region may predict GU relapse." }, { "pmid": "17486089", "year": 2007, "title": "Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals", "title_en": null, "title_de": "Wasserstoff wirkt als therapeutisches Antioxidans, indem er selektiv zytotoxische Sauerstoffradikale reduziert", "journal": "Nature Medicine", "authors": "Ohsawa et al.", "author_search": "ohsawa ohsawa", "doi": "10.1038/nm1577", "doi_url": "https://doi.org/10.1038/nm1577", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/17486089/", "url": "https://h2medicine.org/studies/study-ohsawa-2007-therapeutic-antioxidant-cytotoxic-oxygen-radicals/", "methods": [ "inhalation" ], "indications": [ "fundamentals", "mechanism", "neurology", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2007 · Ohsawa — Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals", "summary": "Hydrogen (H₂) acts as a selective antioxidant: it specifically neutralizes the most aggressive free radical — the hydroxyl radical (•OH) — while leaving the beneficial, signaling oxygen species untouched. In a rat model, inhaled H₂ markedly reduced brain damage after stroke. (Nature Medicine, 2007 — the key study that launched hydrogen research worldwide.)", "assessment": "The single most important study in the field — anyone explaining H₂ starts here. The selectivity argument is also the strongest educational argument: H₂ does not interfere with normal redox signaling, unlike high-dose classical antioxidants (which were even harmful in some studies). For us it provides the scientific foundation for every H₂ product. Limitation, stated honestly: purely preclinical — the leap to humans only comes with later RCTs.", "abstract": "Acute oxidative stress induced by ischemia-reperfusion or inflammation causes serious damage to tissues, and persistent oxidative stress is accepted as one of the causes of many common diseases including cancer. We show here that hydrogen (H(2)) has potential as an antioxidant in preventive and therapeutic applications. We induced acute oxidative stress in cultured cells by three independent methods. H(2) selectively reduced the hydroxyl radical, the most cytotoxic of reactive oxygen species (ROS), and effectively protected cells; however, H(2) did not react with other ROS, which possess physiological roles. We used an acute rat model in which oxidative stress damage was induced in the brain by focal ischemia and reperfusion. The inhalation of H(2) gas markedly suppressed brain injury by buffering the effects of oxidative stress. Thus H(2) can be used as an effective antioxidant therapy; owing to its ability to rapidly diffuse across membranes, it can reach and react with cytotoxic ROS and thus protect against oxidative damage.", "conclusion": "The inhalation of H(2) gas markedly suppressed brain injury by buffering the effects of oxidative stress. Thus H(2) can be used as an effective antioxidant therapy; owing to its ability to rapidly diffuse across membranes, it can reach and react with cytotoxic ROS and thus protect against oxidative damage." }, { "pmid": "17159237", "year": 2006, "title": "Electrolyzed-reduced water protects against oxidative damage to DNA, RNA, and protein.", "title_en": null, "title_de": "Elektrolysiert-reduziertes Wasser schützt vor oxidativen Schäden an DNA, RNA und Protein", "journal": "Applied biochemistry and biotechnology", "authors": "Lee et al.", "author_search": "lee lee", "doi": "10.1385/abab:135:2:133", "doi_url": "https://doi.org/10.1385/abab:135:2:133", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/17159237/", "url": "https://h2medicine.org/studies/study-lee-2006-electrolyzed-reduced-protects-against/", "methods": [ "drinking-hrw" ], "indications": [ "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2006 · Lee et al. — Electrolyzed-reduced water protects against oxidative damage to DNA, RNA, and protein", "summary": "Electrolyzed-reduced water (ERW) — which contains dissolved H₂ — significantly reduced H₂O₂-induced DNA strand breaks in human lymphocytes in the test tube, and also protected RNA and proteins from oxidative damage. Ascorbic acid dissolved in ERW showed roughly three times the antioxidant activity compared to normal water. This is an in-vitro cell study; no conclusions about effects in living humans can be drawn.", "assessment": "An in-vitro study demonstrating antioxidant protective properties of ERW (which contains dissolved H₂) in isolated human cells and biomolecules. The results are internally consistent and the methods are standard. Important limitations: this is a cell/test-tube study — the findings cannot be directly extrapolated to effects in living humans. The study also does not isolate H₂ alone as the causative agent (alkaline pH and other ERW properties were not controlled separately). The results are a useful mechanistic pointer, not clinical evidence.", "abstract": "The generation of reactive oxygen species is thought to cause extensive oxidative damage to various biomolecules such as DNA, RNA, and protein. In this study, the preventive, suppressive, and protective effects of in vitro supplementation with electrolyzed-reduced water on H2O2-induced DNA damage in human lymphocytes were examined using a comet assay. Pretreatment, cotreatment, and posttreatment with electrolyzed-reduced water enhanced human lymphocyte resistance to the DNA strand breaks induced by H2O2 in vitro. Moreover, electrolyzed-reduced water was much more effective than diethylpyrocarbonate-treated water in preventing total RNA degradation at 4 and 25 degrees C. In addition, electrolyzed-reduced water completely prevented the oxidative cleavage of horseradish peroxidase, as determined using sodium dodecyl sulfate-polyacrylamide gels. Enhancement of the antioxidant activity of ascorbic acid dissolved in electrolyzed-reduced water was about threefold that of ascorbic acid dissolved in nonelectrolyzed deionized water, as measured by a xanthine-xanthine oxidase superoxide scavenging assay system, suggesting an inhibitory effect of electrolyzedreduced water on the oxidation of ascorbic acid.", "conclusion": "In addition, electrolyzed-reduced water completely prevented the oxidative cleavage of horseradish peroxidase, as determined using sodium dodecyl sulfate-polyacrylamide gels. Enhancement of the antioxidant activity of ascorbic acid dissolved in electrolyzed-reduced water was about threefold that of ascorbic acid dissolved in nonelectrolyzed deionized water, as measured by a xanthine-xanthine oxida" }, { "pmid": "17125074", "year": 2006, "title": "[Temporary clipping and cerebral blood flow in patients with cerebral aneurysms].", "title_en": null, "title_de": "Temporäres Clipping und zerebraler Blutfluss bei Patienten mit zerebralen Aneurysmen", "journal": "Zhurnal voprosy neirokhirurgii imeni N. N. Burdenko", "authors": "Asaturian et al.", "author_search": "asaturian asaturian", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/17125074/", "url": "https://h2medicine.org/studies/study-asaturian-2006-temporary-clipping-cerebral-blood/", "methods": [], "indications": [ "neurology", "cardiovascular" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "tracer-clearance", "headline": "2006 · Asaturian et al. — Temporary Clipping and Cerebral Blood Flow in Patients with Cerebral Aneurysms", "summary": "This neurosurgery study uses the H₂-inhalation clearance technique to measure regional cerebral blood flow during aneurysm surgery — it is not an H₂ therapy study. H₂ gas serves purely as a measurement tracer for intraoperative blood flow monitoring. The study examines whether temporary vessel clipping during aneurysm surgery causes dangerous ischemia. (Zhurnal voprosy neirokhirurgii imeni N. N. Burdenko, 2006.)", "assessment": "Off-topic for H₂ therapy. H₂-inhalation in this study is a standard intraoperative blood flow measurement technique (H₂ clearance), not a therapeutic intervention. No H₂ was administered for therapeutic purposes. The study is a neurosurgery paper on cerebral blood flow dynamics during aneurysm surgery. Its presence in an H₂ therapy database is a metadata classification error based on the word „H2-inhalation“ in the measurement methods.", "abstract": "Regional cerebral blood flow (RCBF) was measured with cerebral aneurysms by the H2-inhalation technique during intraoperative occlusion test in 15 patients. Temporary clipping was followed by a decrease of RCBF below the critical values in most patients. Reperfusion at the removal of a clip from the internal carotid and middle cerebral artery induced a significant hyperemia (298 +/- 55 ml/100 g x min). At the same time, there was no increase in the frequency of postoperative complications due to temporary clipping. This suggests that their development is related to the duration of cerebral ischemia and the state of the blood-brain barrier.", "conclusion": "At the same time, there was no increase in the frequency of postoperative complications due to temporary clipping. This suggests that their development is related to the duration of cerebral ischemia and the state of the blood-brain barrier." }, { "pmid": "16894148", "year": 2006, "title": "Interstellar chemistry.", "title_en": null, "title_de": "Interstellare Chemie", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "authors": "Klemperer", "author_search": "klemperer klemperer", "doi": "10.1073/pnas.0605352103", "doi_url": "https://doi.org/10.1073/pnas.0605352103", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/16894148/", "url": "https://h2medicine.org/studies/study-klemperer-2006-interstellar-chemistry/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2006 · Klemperer — Interstellar chemistry", "summary": "This theoretical review discusses the molecular chemistry of the interstellar medium, including the role of molecular hydrogen (H₂) and helium ionisation in driving the rich organic chemistry observed in galaxies. It is an astrophysics overview with no connection to biological or health-related applications of H₂.", "assessment": "This is an astrophysics review with no relevance whatsoever to biological effects of molecular hydrogen. H₂ appears only as the most abundant molecule in the universe, playing a role in interstellar ion-molecule chemistry. This paper provides no evidence of any kind regarding H₂ as a health or therapeutic agent.", "abstract": "In the past half century, radioastronomy has changed our perception and understanding of the universe. In this issue of PNAS, the molecular chemistry directly observed within the galaxy is discussed. For the most part, the description of the molecular transformations requires specific kinetic schemes rather than chemical thermodynamics. Ionization of the very abundant molecular hydrogen and atomic helium followed by their secondary reactions is discussed. The rich variety of organic species observed is a challenge for complete understanding. The role and nature of reactions involving grain surfaces as well as new spectroscopic observations of interstellar and circumstellar regions are topics presented in this special feature.", "conclusion": "The rich variety of organic species observed is a challenge for complete understanding. The role and nature of reactions involving grain surfaces as well as new spectroscopic observations of interstellar and circumstellar regions are topics presented in this special feature." }, { "pmid": "16760903", "year": 2006, "title": "Electrolyzed-reduced water reduced hemodialysis-induced erythrocyte impairment in end-stage renal disease patients.", "title_en": null, "title_de": "Elektrolytisch reduziertes Wasser verringerte die hämodialyseinduzierte Erythrozytenschädigung bei Patienten mit terminaler Niereninsuffizienz", "journal": "Kidney international", "authors": "Huang et al.", "author_search": "huang huang", "doi": "10.1038/sj.ki.5001576", "doi_url": "https://doi.org/10.1038/sj.ki.5001576", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/16760903/", "url": "https://h2medicine.org/studies/study-huang-2006-electrolyzed-reduced-reduced-hemodialysis/", "methods": [ "unspecified" ], "indications": [ "metabolic", "kidney-dialysis", "immune-system", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2006 · Huang et al. — Electrolyzed-Reduced Water Reduced Hemodialysis-Induced Erythrocyte Impairment in End-Stage Renal Disease Patients", "summary": "Six months of electrolyzed-reduced water (ERW) treatment in chronic hemodialysis patients reduced oxidative stress, improved red blood cell survival, and attenuated pro-inflammatory cytokines — second only to vitamin C, and without its side effects. ERW outperformed vitamin E-coated dialyzers in most oxidative stress parameters in this 4-arm comparative study. (Kidney International, 2006.)", "assessment": "This is a well-designed comparative study (4 arms, 15 patients each) published in a high-impact journal. The oxidative stress findings are consistent and clinically meaningful for the hemodialysis population. Limitations: Not randomized — patient assignment method not detailed; small group sizes (n=15 per arm) limit statistical power for some outcomes. ERW concentration of dissolved H₂ is not precisely reported, making cross-study comparisons difficult. The mechanism is plausible (H₂ as selective antioxidant neutralizing ROS from dialysis), but the ERW formulation also differs from simple hydrogen-rich water. The 6-month hematocrit improvement and cytokine reduction are encouraging but need replication in larger, randomized trials. Notably, the absence of oxalate accumulation is a practical clinical advantage over vitamin C in dialysis patients.", "abstract": "Chronic hemodialysis (HD) patients increase erythrocyte susceptibility to hemolysis and impair cell survival. We explored whether electrolyte-reduced water (ERW) could palliate HD-evoked erythrocyte impairment and anemia. Forty-three patients undergoing chronic HD were enrolled and received ERW administration for 6 month. We evaluated oxidative stress in blood and plasma, erythrocyte methemoglobin (metHb)/ferricyanide reductase activity, plasma metHb, and proinflammatory cytokines in the chronic HD patients without treatment (n=15) or with vitamin C (VC)- (n=15), vitamin E (VE)-coated dialyzer (n=15), or ERW treatment (n=15) during an HD course. The patients showed marked increases (15-fold) in blood reactive oxygen species, mostly H(2)O(2), after HD without any treatment. HD resulted in decreased plasma VC, total antioxidant status, and erythrocyte metHb/ferricyanide reductase activity and increased erythrocyte levels of phosphatidylcholine hydroperoxide (PCOOH) and plasma metHb. Antioxidants treatment significantly palliated single HD course-induced oxidative stress, plasma and RBC PCOOH, and plasma metHb levels, and preserved erythrocyte metHb /ferricyanide reductase activity in an order VC>ERW>VE-coated dialyzer. However, ERW had no side effects of oxalate accumulation easily induced by VC. Six-month ERW treatment increased hematocrit and attenuated proinflammatory cytokines profile in the HD patients. In conclusion, ERW treatment administration is effective in palliating HD-evoked oxidative stress, as indicated by lipid peroxidation, hemolysis, and overexpression of proinflammatory cytokines in HD patients.", "conclusion": "Six-month ERW treatment increased hematocrit and attenuated proinflammatory cytokines profile in the HD patients. In conclusion, ERW treatment administration is effective in palliating HD-evoked oxidative stress, as indicated by lipid peroxidation, hemolysis, and overexpression of proinflammatory cytokines in HD patients." }, { "pmid": "15679729", "year": 2005, "title": "Birth-related increase in intracolonic hydrogen gas and nitric oxide as indicator of host-microbial interactions.", "title_en": null, "title_de": "Geburtsbedingter Anstieg von intrakolonischem Wasserstoffgas und Stickstoffmonoxid als Indikator für Wirt-Mikroben-Interaktionen", "journal": "Allergy", "authors": "Sobko et al.", "author_search": "sobko sobko", "doi": "10.1111/j.1398-9995.2005.00737.x", "doi_url": "https://doi.org/10.1111/j.1398-9995.2005.00737.x", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/15679729/", "url": "https://h2medicine.org/studies/study-sobko-2005-birth-related-increase-intracolonic/", "methods": [], "indications": [ "liver", "immune-system", "allergy" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "byproduct", "headline": "2005 · Sobko et al. — Birth-Related Increase in Intracolonic Hydrogen Gas and Nitric Oxide as Indicator of Host-Microbial Interactions", "summary": "This study measured endogenous hydrogen gas produced by gut bacteria in 32 newborns during the first 6 months of life to monitor intestinal colonization — it is not an H₂ therapy study. Intracolonic H₂ was used as a marker of bacterial fermentation activity to understand the development of the infant microbiome and its potential link to allergy development. (Allergy, 2005.)", "assessment": "Off-topic for H₂ therapy. This study investigates endogenous, bacterially produced colonic H₂ as a biomarker of gut microbiome colonization in newborns. No H₂ was administered. The H₂ measured is entirely produced by intestinal bacteria. While this is interesting microbiome research published in a respected allergy journal, it has no connection to therapeutic molecular hydrogen medicine.", "abstract": "BACKGROUND: Bacterial colonization of the intestine early in life might have implications for allergy development. We studied early host-bacterial interactions in the gut by simultaneous measurements of hydrogen gas (H(2)) and faecal short chain fatty acid pattern (SCFAs), i.e. bacterial products, as well as of nitric oxide (NO), a marker of mucosal immune activation. METHODS: A novel minimally invasive technique was used for repeated measurements of luminal colonic H(2) and NO in 32 healthy newborn infants delivered vaginally or by Caesarean section. Luminal gas was sampled and analysed at five occasions: immediately after birth, day 1, days 3-5, 1 and 5-6 months after birth. RESULTS: Colonic H(2), NO and faecal SCFAs were undetectable at birth. The H(2) and SCFAs appeared within 24 h and continued to increase during the 6 months follow-up. Nitric oxide remained very low until 3-5 days after birth at which time it markedly increased. In some apparently healthy infants NO transiently reached levels similar to those seen in adults with inflammatory bowel disease. CONCLUSION: Intracolonic measurements of H(2) and NO may be useful to monitor the developmental colonization process as well as mucosal responses.", "conclusion": "Intracolonic measurements of H(2) and NO may be useful to monitor the developmental colonization process as well as mucosal responses." }, { "pmid": "15667272", "year": 2005, "title": "Use of molecular hydrogen as an energy substrate by human pathogenic bacteria.", "title_en": null, "title_de": "Nutzung von molekularem Wasserstoff als Energiesubstrat durch humanpathogene Bakterien", "journal": "Biochemical Society transactions", "authors": "Maier", "author_search": "maier maier", "doi": "10.1042/bst0330083", "doi_url": "https://doi.org/10.1042/bst0330083", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/15667272/", "url": "https://h2medicine.org/studies/study-maier-2005-use-energy-substrate-pathogenic/", "methods": [ "unspecified" ], "indications": [ "liver", "respiratory", "womens-health" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2005 · Maier — Use of molecular hydrogen as an energy substrate by human pathogenic bacteria", "summary": "Several pathogenic bacteria — including Helicobacter pylori (stomach), Helicobacter hepaticus (liver), and Salmonella — can use molecular hydrogen (H₂) produced in the gut as a respiratory fuel, and this ability significantly enhances their capacity to colonise and cause disease in animals. This is a microbiology/animal study — not a human clinical study, and not about H₂ supplementation as a health intervention.", "assessment": "An animal/in-vitro microbiology study showing that gut-produced H₂ fuels the virulence of several pathogenic bacteria (H. pylori, H. hepaticus, Salmonella) in mouse models. This is not a study of H₂ as a health supplement or therapeutic agent — the H₂ here benefits the bacteria, not the host. These findings do not contradict beneficial H₂ effects in other contexts, but they add important biological complexity: H₂ in the gut is a substrate used by multiple microorganisms, including pathogens. Findings are from animal/cell experiments and cannot be directly extrapolated to human H₂ supplementation outcomes.", "abstract": "Molecular hydrogen is produced as a fermentation by-product in the large intestine of animals and its production can be correlated with the digestibility of the carbohydrates consumed. Pathogenic Helicobacter species (Helicobacter pylori and H. hepaticus) have the ability to use H(2) through a respiratory hydrogenase, and it was demonstrated that the gas is present in the tissues colonized by these pathogens (the stomach and the liver respectively of live animals). Mutant strains of H. pylori unable to use H(2) are deficient in colonizing mice compared with the parent strain. On the basis of available annotated gene sequence information, the enteric pathogen Salmonella, like other enteric bacteria, contains three putative membrane-associated H(2)-using hydrogenase enzymes. From the analysis of gene-targeted mutants it is concluded that each of the three membrane-bound hydrogenases of Salmonella enterica serovar Typhimurium are coupled with an H(2)-oxidizing respiratory pathway. From microelectrode probe measurements on live mice, H(2) could be detected at approx. 50 muM levels within the tissues (liver and spleen), which are colonized by Salmonella. The half-saturation affinity of whole cells of these pathogens for H(2) is much less than this, so it is expected that the (H(2)-utilizing) hydrogenase enzymes be saturated with the reducing substrate in vivo. All three enteric NiFe hydrogenase enzymes contribute to virulence of the bacterium in a typhoid fever-mouse model, and the combined removal of all three hydrogenases resulted in a strain that is avirulent and (in contrast with the parent strain) one that is not able to pass the intestinal tract to invade liver or spleen tissue. It is proposed that H(2) utilization and specifically its oxidation, coupled with a respiratory pathway, is required for energy production to permit growth and maintain efficient virulence of a number of pathogenic bacteria during infection of animals. These would be expected to include the Campylobacter jejuni, a bacterium closely related to Helicobacter, as well as many enteric bacteria (Escherichia coli, Shigella and Yersinia species).", "conclusion": "It is proposed that H(2) utilization and specifically its oxidation, coupled with a respiratory pathway, is required for energy production to permit growth and maintain efficient virulence of a number of pathogenic bacteria during infection of animals. These would be expected to include the Campylobacter jejuni, a bacterium closely related to Helicobacter, as well as many enteric bacteria (Escheri" }, { "pmid": "15578160", "year": 2005, "title": "Isolation and characterisation of an equol-producing mixed microbial culture from a human faecal sample and its activity under gastrointestinal conditions.", "title_en": null, "title_de": "Isolierung und Charakterisierung einer equolproduzierenden gemischten mikrobiellen Kultur aus einer menschlichen Stuhlprobe und ihre Aktivität unter gastrointestinalen Bedingungen", "journal": "Archives of microbiology", "authors": "Decroos et al.", "author_search": "decroos decroos", "doi": "10.1007/s00203-004-0747-4", "doi_url": "https://doi.org/10.1007/s00203-004-0747-4", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/15578160/", "url": "https://h2medicine.org/studies/study-decroos-2005-isolation-characterisation-equol-producing/", "methods": [ "inhalation" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2005 · Decroos et al. — Isolation and characterisation of an equol-producing mixed microbial culture from a human faecal sample and its activity under gastrointestinal conditions", "summary": "This in-vitro gut microbiome study shows that hydrogen gas produced during gut fermentation stimulates equol production by a mixed bacterial culture derived from human stool. Equol is a metabolite of the soy isoflavone daidzein with potential hormonal and antioxidant activity. The role of H₂ here is as a microbial fermentation by-product that modulates gut microbiome metabolism — not a human health intervention.", "assessment": "An in-vitro gut microbiome study with a peripheral connection to H₂: endogenously produced fermentation H₂ stimulates bacterial equol synthesis in culture. This is not a study of exogenous H₂ supplementation as a health intervention. Findings are from in-vitro bacterial cultures; they do not directly translate to effects of drinking hydrogen-enriched water or inhaling H₂. The study is a niche piece of gut microbiome research with no direct clinical implications for H₂ therapy.", "abstract": "Only about one third of humans possess a microbiota capable of transforming the dietary isoflavone daidzein into equol. Little is known about the dietary and physiological factors determining this ecological feature. In this study, the in vitro metabolism of daidzein by faecal samples from four human individuals was investigated. One culture produced the metabolites dihydrodaidzein and O-desmethylangolensin, another produced dihydrodaidzein and equol. From the latter, a stable and transferable mixed culture transforming daidzein into equol was obtained. Molecular fingerprinting analysis (denaturing gradient gel electrophoresis) showed the presence of four bacterial species of which only the first three strains could be brought into pure culture. These strains were identified as Lactobacillus mucosae EPI2, Enterococcus faecium EPI1 and Finegoldia magna EPI3, and did not produce equol in pure culture. The fourth species was tentatively identified as Veillonella sp strain EP. It was found that hydrogen gas in particular, but also butyrate and propionate, which are all colonic fermentation products from poorly digestible carbohydrates, stimulated equol production by the mixed culture. However, when fructo-oligosaccharides were added, equol production was inhibited. Furthermore, the equol-producing capacity of the isolated culture was maintained upon its addition to a faecal culture originating from a non-equol-producing individual.", "conclusion": "However, when fructo-oligosaccharides were added, equol production was inhibited. Furthermore, the equol-producing capacity of the isolated culture was maintained upon its addition to a faecal culture originating from a non-equol-producing individual." }, { "pmid": "15085273", "year": 2004, "title": "Hydrogen storage methods.", "title_en": null, "title_de": "Methoden zur Wasserstoffspeicherung", "journal": "Die Naturwissenschaften", "authors": "Züttel", "author_search": "züttel züttel", "doi": "10.1007/s00114-004-0516-x", "doi_url": "https://doi.org/10.1007/s00114-004-0516-x", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/15085273/", "url": "https://h2medicine.org/studies/study-zuettel-2004-storage-methods/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "sports-exercise" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2004 · Züttel — Hydrogen storage methods", "summary": "This theoretical engineering review surveys six methods for storing hydrogen gas — from high-pressure cylinders and liquid H₂ cryotanks to metal hydrides — and assesses their volumetric density, gravimetric performance, and practical limitations for energy applications. This is materials science and energy technology; it has no connection to therapeutic or biological use of molecular hydrogen.", "assessment": "This is a materials science and energy technology review with no relevance to H₂ as a health or therapeutic agent. It addresses H₂ storage for future energy systems — vehicles, power grids — not biological applications. The paper provides no evidence, positive or negative, regarding any health effect of molecular hydrogen.", "abstract": "Hydrogen exhibits the highest heating value per mass of all chemical fuels. Furthermore, hydrogen is regenerative and environmentally friendly. There are two reasons why hydrogen is not the major fuel of today's energy consumption. First of all, hydrogen is just an energy carrier. And, although it is the most abundant element in the universe, it has to be produced, since on earth it only occurs in the form of water and hydrocarbons. This implies that we have to pay for the energy, which results in a difficult economic dilemma because ever since the industrial revolution we have become used to consuming energy for free. The second difficulty with hydrogen as an energy carrier is its low critical temperature of 33 K (i.e. hydrogen is a gas at ambient temperature). For mobile and in many cases also for stationary applications the volumetric and gravimetric density of hydrogen in a storage material is crucial. Hydrogen can be stored using six different methods and phenomena: (1) high-pressure gas cylinders (up to 800 bar), (2) liquid hydrogen in cryogenic tanks (at 21 K), (3) adsorbed hydrogen on materials with a large specific surface area (at T<100 K), (4) absorbed on interstitial sites in a host metal (at ambient pressure and temperature), (5) chemically bonded in covalent and ionic compounds (at ambient pressure), or (6) through oxidation of reactive metals, e.g. Li, Na, Mg, Al, Zn with water. The most common storage systems are high-pressure gas cylinders with a maximum pressure of 20 MPa (200 bar). New lightweight composite cylinders have been developed which are able to withstand pressures up to 80 MPa (800 bar) and therefore the hydrogen gas can reach a volumetric density of 36 kg.m(-3), approximately half as much as in its liquid state. Liquid hydrogen is stored in cryogenic tanks at 21.2 K and ambient pressure. Due to the low critical temperature of hydrogen (33 K), liquid hydrogen can only be stored in open systems. The volumetric density of liquid hydrogen is 70.8 kg.m(-3), and large volumes, where the thermal losses are small, can cause hydrogen to reach a system mass ratio close to one. The highest volumetric densities of hydrogen are found in metal hydrides. Many metals and alloys are capable of reversibly absorbing large amounts of hydrogen. Charging can be done using molecular hydrogen gas or hydrogen atoms from an electrolyte. The group one, two and three light metals (e.g. Li, Mg, B, Al) can combine with hydrogen to form a large variety of metal-hydrogen complexes. These are especially interesting because of their light weight and because of the number of hydrogen atoms per metal atom, which is two in many cases. Hydrogen can also be stored indirectly in reactive metals such as Li, Na, Al or Zn. These metals easily react with water to the corresponding hydroxide and liberate the hydrogen from the water. Since water is the product of the combustion of hydrogen with either oxygen or air, it can be recycled in a closed loop and react with the metal. Finally, the metal hydroxides can be thermally reduced to metals in a solar furnace. This paper reviews the various storage methods for hydrogen and highlights their potential for improvement and their physical limitations.", "conclusion": "Finally, the metal hydroxides can be thermally reduced to metals in a solar furnace. This paper reviews the various storage methods for hydrogen and highlights their potential for improvement and their physical limitations." }, { "pmid": "15762476", "year": 2004, "title": "[Studies on human breast cancer tissues with Raman microspectroscopy].", "title_en": null, "title_de": "Untersuchungen an menschlichem Brustkrebsgewebe mittels Raman-Mikrospektroskopie", "journal": "Guang pu xue yu guang pu fen xi = Guang pu", "authors": "Yu et al.", "author_search": "yu yu", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/15762476/", "url": "https://h2medicine.org/studies/study-yu-2004-breast-cancer-tissues-raman/", "methods": [ "unspecified" ], "indications": [ "metabolic", "cancer" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2004 · Yu et al. — Studies on human breast cancer tissues with Raman microspectroscopy", "summary": "This in-vitro spectroscopy study uses Raman microspectroscopy to identify molecular differences between normal and malignant human breast tissue samples, finding changes in nucleic acids, proteins, and lipids in cancer tissue. Molecular hydrogen (H₂) is mentioned only peripherally — the paper notes that hydrogen bonds in proteins are disrupted in cancer tissue. There is no H₂ intervention or supplementation aspect.", "assessment": "This is an in-vitro tissue spectroscopy study about breast cancer tissue characterisation using Raman microspectroscopy. The word „hydrogen“ in the abstract refers to chemical hydrogen bonds within proteins — not to molecular hydrogen (H₂) gas. This paper has no relevance to H₂ supplementation, antioxidant H₂, or any therapeutic H₂ application.", "abstract": "The microscopic Raman spectra from normal and malignant human breast tissues have been measured and investigated. The spectral differences and changes between normal and malignant breast tissue samples mainly involve: (1) the band from the symmetric stretching modes of PO2- group in the DNA shifts from 1082 to 1097 cm(-1) and becomes stronger. The intensity of the symmetric stretching modes of O-P-O at 817 cm(-1) in RNA increases greatly. (2) The bands of Amide I and III at 1657 and 1273 cm(-1) change to 1662 and 1264 cm(-1) respectively with their intensity and band width increasing. The peak of the C-O stretching modes in the amino acids shifts to higher wave number. The tryptophan band at 1368 cm(-1) almost disappears. (3) Fewer characteristic Raman bands from lipids are observed. These spectral changes indicate that nucleic acids increase in contents relatively, while their conformation changes in cancer tissues. The proteins show various conformations and disorder structures with their molecular hydrogen bonds nearly broken. The contents of lipids decrease obviously. This investigation shows that Raman microspectroscopy is useful to biochemical study and vivo diagnosis of human breast cancers.", "conclusion": "The contents of lipids decrease obviously. This investigation shows that Raman microspectroscopy is useful to biochemical study and vivo diagnosis of human breast cancers." }, { "pmid": "15561487", "year": 2004, "title": "Bioavailability of cellobiose by tolerance test and breath hydrogen excretion in humans.", "title_en": null, "title_de": "Bioverfügbarkeit von Cellobiose mittels Toleranztest und Atemwasserstoffausscheidung beim Menschen", "journal": "Nutrition (Burbank, Los Angeles County, Calif.)", "authors": "Nakamura et al.", "author_search": "nakamura nakamura", "doi": "10.1016/j.nut.2004.08.005", "doi_url": "https://doi.org/10.1016/j.nut.2004.08.005", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/15561487/", "url": "https://h2medicine.org/studies/study-nakamura-2004-bioavailability-cellobiose-tolerance-test/", "methods": [], "indications": [ "fundamentals-safety" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "breath-test", "headline": "2004 · Nakamura et al. — Bioavailability of Cellobiose by Tolerance Test and Breath Hydrogen Excretion in Humans", "summary": "This nutrition study uses breath hydrogen excretion to assess how cellobiose (a disaccharide) is fermented in the large intestine — it is not an H₂ therapy study. Breath H₂ is used as a standard clinical marker for detecting undigested carbohydrate reaching the colon, estimating the available energy from cellobiose at approximately 2 kcal/g. (Nutrition, 2004.)", "assessment": "Off-topic for H₂ therapy. This is a clinical nutrition study measuring fermentation of a dietary disaccharide using breath hydrogen as a standard metabolic assessment tool. No H₂ was administered therapeutically. The breath H₂ measured is produced by colonic bacteria fermenting undigested cellobiose. The source metadata classification (methods: „inhalation, drinking-hrw“) is a clear error. This study belongs to dietary fiber and prebiotic research.", "abstract": "OBJECTIVE: Prebiotic substances have the property of intestinal fermentation. Cellobiose has a beta-1,4 linkage, so it is resistant to hydrolysis by human small intestinal disaccharidase and, hence, reaches the colon undigested. Until this study, it was unclear whether cellobiose has fermentability or bioavailability. The objectives of this study were to clarify whether cellobiose is fermented in the large intestine and to estimate the available energy from cellobiose intake by using tolerance tests and breath hydrogen tests in healthy female subjects. METHODS: Ten healthy young women (20.5 +/- 2.1 y) who did not develop diarrhea after ingesting 30 g of cellobiose in a previous experiment were recruited. Tolerance tests and breath hydrogen tests for 25 g of cellobiose or glucose were carried out at least 2 wk apart. Blood samples were collected before and at 30-min intervals up to 3 h after ingestion. Breath gas samples were collected simultaneously before and at 30-min intervals up to 6 h after ingestion of cellobiose or glucose. Blood glucose and insulin levels and the concentration of breath hydrogen were analyzed. RESULTS: When 25 g of cellobiose was ingested, there was no increase in blood glucose or insulin secretion, but these markers increased remarkably with glucose ingestion. The excretion of breath hydrogen gas after cellobiose ingestion was significantly greater than that after glucose ingestion. CONCLUSIONS: Orally ingested cellobiose was well fermented in human large intestine, and its available energy was estimated to be about 2 kcal/g.", "conclusion": "Orally ingested cellobiose was well fermented in human large intestine, and its available energy was estimated to be about 2 kcal/g." }, { "pmid": "14554258", "year": 2003, "title": "Availability and use of molecular hydrogen as an energy substrate for Helicobacter species.", "title_en": null, "title_de": "Verfügbarkeit und Nutzung von molekularem Wasserstoff als Energiesubstrat für Helicobacter-Arten", "journal": "Microbes and infection", "authors": "Maier", "author_search": "maier maier", "doi": "10.1016/j.micinf.2003.08.002", "doi_url": "https://doi.org/10.1016/j.micinf.2003.08.002", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/14554258/", "url": "https://h2medicine.org/studies/study-maier-2003-availability-use-energy-substrate/", "methods": [ "unspecified" ], "indications": [ "liver", "respiratory" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2003 · Maier — Availability and use of molecular hydrogen as an energy substrate for Helicobacter species", "summary": "This review summarises evidence that the gastric pathogen Helicobacter pylori and the liver pathogen H. hepaticus can use molecular hydrogen (H₂) — produced by gut fermentation — as a respiratory energy source, and that this H₂ utilisation substantially enhances their ability to colonise the stomach. This is a microbiology literature review about bacterial energy metabolism, not a study of H₂ as a health supplement.", "assessment": "A microbiology review documenting that gut-produced H₂ fuels Helicobacter virulence — a context where H₂ benefits pathogens, not the human host. This review provides no evidence for or against beneficial effects of exogenous H₂ supplementation in humans. It is a literature synthesis, not a new experiment. The described mechanism — H₂ as bacterial energy substrate — is well-documented but biologically distinct from the antioxidant/signalling mechanisms proposed in H₂ health research.", "abstract": "Molecular hydrogen is produced in the large intestine of animals due to the fermentation reactions of sugar catabolism. The gastric pathogen Helicobacter pylori and the liver pathogen Helicobacter hepaticus have the capacity to use molecular hydrogen as a respiratory substrate. The amount of the gas within tissues colonized by these pathogens is ample, and use of H2 significantly increases the stomach colonization ability of H. pylori.", "conclusion": "The amount of the gas within tissues colonized by these pathogens is ample, and use of H2 significantly increases the stomach colonization ability of H. pylori." }, { "pmid": "14698375", "year": 2003, "title": "Detection of flatus using a portable hydrogen gas analyzer.", "title_en": null, "title_de": "Nachweis von Darmgas mit einem tragbaren Wasserstoffgas-Analysator.", "journal": "Journal of clinical anesthesia", "authors": "Terai et al.", "author_search": "terai terai", "doi": "10.1016/j.jclinane.2003.03.001", "doi_url": "https://doi.org/10.1016/j.jclinane.2003.03.001", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/14698375/", "url": "https://h2medicine.org/studies/study-terai-2003-detection-flatus-portable-analyzer/", "methods": [], "indications": [ "other" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "breath-test", "headline": "2003 · Terai — Detection of flatus using a portable hydrogen gas analyzer.", "summary": "A portable hydrogen gas analyzer was used to detect and measure intestinal gas (flatus) in human subjects. In this study, H₂ is employed as a diagnostic breath/gas marker of gut fermentation — not as a therapeutic agent administered to subjects. (Journal of Clinical Anesthesia, 2003.)", "assessment": "Assessment note: This study is not an H₂ therapy trial. Hydrogen gas here is solely a diagnostic biomarker — an endogenous product of colonic fermentation used to assess gut function. No H₂ was administered therapeutically. The abstract was not provided in the source data; a full reading of the original paper (DOI: 10.1016/j.jclinane.2003.03.001) is required before drawing any further conclusions. No efficacy claims about H₂ therapy can be derived from this work.", "abstract": null, "conclusion": null }, { "pmid": "12947435", "year": 2003, "title": "Comparison of digestibility and breath hydrogen gas excretion of fructo-oligosaccharide, galactosyl-sucrose, and isomalto-oligosaccharide in healthy human subjects.", "title_en": null, "title_de": "Vergleich der Verdaulichkeit und Atemwasserstoff-Ausscheidung von Fructo-Oligosacchariden, Galactosyl-Saccharose und Isomalto-Oligosacchariden bei gesunden menschlichen Probanden.", "journal": "European journal of clinical nutrition", "authors": "Oku et al.", "author_search": "oku oku", "doi": "10.1038/sj.ejcn.1601666", "doi_url": "https://doi.org/10.1038/sj.ejcn.1601666", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/12947435/", "url": "https://h2medicine.org/studies/study-oku-2003-comparison-digestibility-breath-excretion/", "methods": [], "indications": [ "other" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "breath-test", "headline": "2003 · Oku — Comparison of digestibility and breath hydrogen gas excretion of fructo-oligosaccharide, galactosyl-sucrose, and isomalto-oligosaccharide in healthy human subjects.", "summary": "Breath hydrogen excretion was used as a diagnostic marker to compare how well three different dietary oligosaccharides (FOS, GS, IMO) are digested in the small intestine versus fermented in the large intestine of healthy adults. H₂ here is an endogenous fermentation product measured in breath — not a therapeutic agent. (European Journal of Clinical Nutrition, 2003.)", "assessment": "Assessment note: This study is not an H₂ therapy trial. H₂ is measured as an endogenous breath biomarker of gut fermentation, not administered as a therapeutic agent. The finding that FOS and GS are not fully digested in the small intestine (and thus fermented in the colon) is relevant for prebiotic dietary fiber research, but not for H₂ medicine. Limitations: the cohort is small (9 males, 29 females) and entirely healthy; no clinical endpoints assessed. No therapeutic claims can be derived.", "abstract": "OBJECTIVES: To clarify the difference of digestibility in the small intestine among fructo-oligosaccharide (FOS), galactosyl-sucrose (GS), and isomalto-oligosaccharide (IMO) using breath hydrogen test. DESIGN: The first step: screening test of breath hydrogen excretion and FOS tolerance test to select the subjects. The second step: breath hydrogen test of three kinds of oligosaccharides, carried out using precautionary regulations. The ingestion order was 10 g of FOS, GS, and IMO, with increases, at 1-week interval, up to 20 g, respectively. Breath gas was collected before, at 20 min intervals from 40 to 120 min after, and at 30 min intervals from 120 min to 7 h after ingestion of test substance. SETTING: Laboratory of Public Health Nutrition, Department of Nutrition and Health Sciences, Siebold University of Nagasaki, Nagasaki, Japan. SUBJECTS: A total of nine males (average: age 25.7+/-3.5 y, weight 61.9+/-8.8 kg, height 170.0+/-6.0 cm) and 29 females (average: 23.1+/-7.2 y, 52.9+/-5.3 kg, 157.5+/-5.1 cm) from the University of Tokyo and Siebold University of Nagasaki. MAIN OUTCOME MEASURES: Breath hydrogen excretion from end-expiratory gas. RESULT: : Breath hydrogen of FOS was more remarkably excreted than that of GS; that of IMO was slight; and that of AUC (10 g) was significantly different. FOS was 9768+/-3253 ppm, GS was 3662+/-2632 ppm, and IMO was 831+/-1154 ppm. A dose dependence was observed at doses between 10 and 20 g of FOS and GS, and the initial time of 20 g was earlier than that of 10 g. CONCLUSIONS: FOS was not hydrolyzed, GS was slightly hydrolyzed, and IMO was readily hydrolyzed by small intestinal enzymes. H(2) gas reflected fermentability in the large intestine. SPONSORSHIP: Siebold University of Nagasaki.", "conclusion": "FOS was not hydrolyzed, GS was slightly hydrolyzed, and IMO was readily hydrolyzed by small intestinal enzymes. H(2) gas reflected fermentability in the large intestine." }, { "pmid": "12846769", "year": 2003, "title": "Reduced hemodialysis-induced oxidative stress in end-stage renal disease patients by electrolyzed reduced water.", "title_en": null, "title_de": "Verringerter hämodialyseinduzierter oxidativer Stress bei Patienten mit terminaler Niereninsuffizienz durch elektrolytisch reduziertes Wasser.", "journal": "Kidney international", "authors": "Huang et al.", "author_search": "huang huang", "doi": "10.1046/j.1523-1755.2003.00118.x", "doi_url": "https://doi.org/10.1046/j.1523-1755.2003.00118.x", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/12846769/", "url": "https://h2medicine.org/studies/study-huang-2003-reduced-hemodialysis-induced-oxidative/", "methods": [ "drinking-hrw" ], "indications": [ "metabolic", "sports-exercise", "cardiovascular", "kidney-dialysis", "immune-system", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": true, "h2category": "therapy", "headline": "2003 · Huang — Reduced hemodialysis-induced oxidative stress in end-stage renal disease patients by electrolyzed reduced water.", "summary": "Patients with end-stage renal disease (ESRD) undergoing chronic hemodialysis showed significantly reduced oxidative stress markers and improved antioxidant status after one month of drinking electrolyzed reduced water (ERW). Inflammatory markers (IL-6, CRP) and oxidized lipid and protein levels were also lowered. (Kidney International, 2003.)", "assessment": "This is one of the earliest published clinical studies specifically examining ERW (as an H₂ source) in a human patient population with a measurable disease endpoint. The results are positive across multiple oxidative and inflammatory markers over one month, which is encouraging. Limitations to state honestly: the sample size is not reported in the available data (the full paper must be consulted for n); no randomized placebo control is described in the abstract; the one-month follow-up is short; ERW composition (H₂ concentration) is not explicitly quantified. The study predates the 2007 Nature Medicine paper that launched the modern H₂ therapy field, making it an important early data point. Results should be interpreted as hypothesis-generating rather than definitive.", "abstract": "BACKGROUND: Increased oxidative stress in end-stage renal disease (ESRD) patients may oxidize macromolecules and consequently lead to cardiovascular events during chronic hemodialysis. Electrolyzed reduced water (ERW) with reactive oxygen species (ROS) scavenging ability may have a potential effect on reduction of hemodialysis-induced oxidative stress in ESRD patients. METHODS: We developed a chemiluminescence emission spectrum and high-performance liquid chromatography analysis to assess the effect of ERW replacement on plasma ROS (H2O2 and HOCl) scavenging activity and oxidized lipid or protein production in ESRD patients undergoing hemodialysis. Oxidized markers, dityrosine, methylguanidine, and phosphatidylcholine hydroperoxide, and inflammatory markers, interleukin 6 (IL-6), and C-reactive protein (CRP) were determined. RESULTS: Although hemodialysis efficiently removes dityrosine and creatinine, hemodialysis increased oxidative stress, including phosphatidylcholine hydroperoxide, and methylguanidine. Hemodialysis reduced the plasma ROS scavenging activity, as shown by the augmented reference H2O2 and HOCl counts (Rh2o2 and Rhocl, respectively) and decreased antioxidative activity (expressed as total antioxidant status in this study). ERW administration diminished hemodialysis-enhanced Rh2o2 and Rhocl, minimized oxidized and inflammatory markers (CRP and IL-6), and partly restored total antioxidant status during 1-month treatment. CONCLUSION: This study demonstrates that hemodialysis with ERW administration may efficiently increase the H2O2- and HOCl-dependent antioxidant defense and reduce H2O2- and HOCl-induced oxidative stress.", "conclusion": "This study demonstrates that hemodialysis with ERW administration may efficiently increase the H2O2- and HOCl-dependent antioxidant defense and reduce H2O2- and HOCl-induced oxidative stress." }, { "pmid": "12121756", "year": 2002, "title": "Fe-only hydrogenases: structure, function and evolution.", "title_en": null, "title_de": "Fe-only-Hydrogenasen: Struktur, Funktion und Evolution", "journal": "Journal of inorganic biochemistry", "authors": "Nicolet et al.", "author_search": "nicolet nicolet", "doi": "10.1016/s0162-0134(02)00392-6", "doi_url": "https://doi.org/10.1016/s0162-0134(02)00392-6", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/12121756/", "url": "https://h2medicine.org/studies/study-nicolet-2002-only-hydrogenases-structure-function/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2002 · Nicolet et al. — Fe-only hydrogenases: structure, function and evolution", "summary": "This biochemistry review covers the molecular structure, catalytic mechanism, and evolutionary origins of iron-only hydrogenase enzymes — proteins that catalyse the reversible conversion between molecular hydrogen (H₂) and protons/electrons. It is a fundamental biochemistry review about enzyme structure; it has no connection to therapeutic H₂ supplementation or H₂ health effects.", "assessment": "A structural biochemistry and evolutionary review of iron-only hydrogenase enzymes. The paper contributes to the fundamental science of how biological systems handle H₂ at the molecular level, but it is not a health or supplementation study. It provides mechanistic context for H₂ biology without any clinical, nutritional, or therapeutic implications.", "abstract": "Hydrogenases are enzymes capable of catalyzing the oxidation of molecular hydrogen or its production from protons and electrons according to the reversible reaction: H(2)<==>2H(+)+2e(-). Most of these enzymes fall into to major classes: NiFe and Fe-only hydrogenases. Extensive spectroscopic, electrochemical and structural studies have shed appreciable light on the catalytic mechanism of hydrogenases. Although evolutionarily unrelated, NiFe and Fe-hydrogenases share a common, unusual feature: an active site low-spin Fe center with CO and CN coordination. We have recently focused our attention on Fe-hydrogenases because from structural studies by us and others, it appears to be a simpler system than the NiFe counterpart. Thus the primary hydrogen binding site has been identified and plausible, electron, proton and hydrogen pathways from and to the buried active site may be proposed from the structural data. The extensive genome sequencing effort currently under way has shown that eukaryotic organisms contain putatively gene coding sequences that display significant homology to Fe-hydrogenases. Here, we summarize the available evidence concerning the mechanism of these enzymes and carry out a structural comparison between Fe-hydrogenases and related proteins of unknown metal content from yeast, plant, worm, insect and mammals.", "conclusion": "The extensive genome sequencing effort currently under way has shown that eukaryotic organisms contain putatively gene coding sequences that display significant homology to Fe-hydrogenases. Here, we summarize the available evidence concerning the mechanism of these enzymes and carry out a structural comparison between Fe-hydrogenases and related proteins of unknown metal content from yeast, plant," }, { "pmid": "11899097", "year": 2002, "title": "Melatonin, mitochondrial homeostasis and mitochondrial-related diseases.", "title_en": null, "title_de": "Melatonin, mitochondriale Homöostase und mitochondrienbedingte Erkrankungen", "journal": "Current topics in medicinal chemistry", "authors": "Acuña Castroviejo et al.", "author_search": "acuña castroviejo acuña castroviejo", "doi": "10.2174/1568026023394344", "doi_url": "https://doi.org/10.2174/1568026023394344", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/11899097/", "url": "https://h2medicine.org/studies/study-acunacastroviejo-2002-melatonin-mitochondrial-homeostasis-mitochondrial/", "methods": [ "drinking-hrw" ], "indications": [ "sports-exercise", "neurology", "oxidative-stress" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "2002 · Acuña Castroviejo et al. — Melatonin, mitochondrial homeostasis and mitochondrial-related diseases", "summary": "This review covers melatonin's antioxidant role in protecting mitochondria from reactive oxygen species (ROS), and its potential relevance to neurodegenerative and neuromuscular diseases. Molecular hydrogen (H₂) appears only in the context of the „hydrogen hypothesis“ of eukaryotic evolution — a theoretical evolutionary model entirely unrelated to H₂ supplementation. This is a theoretical/review paper; no clinical evidence is presented.", "assessment": "A theoretical/narrative review about melatonin and mitochondrial biology. Molecular hydrogen is mentioned only as part of an evolutionary origin hypothesis for eukaryotic cells — the „hydrogen hypothesis“ of endosymbiosis. This paper provides no evidence about H₂ supplementation, H₂ antioxidant effects, or any therapeutic H₂ application. It is a review, not a new experiment, and its H₂ content is purely evolutionary-theoretical.", "abstract": "The recently described 'hydrogen hypothesis' invokes metabolic symbiosis as the driving force for a symbiotic association between an anaerobic, strictly hydrogen-dependent organism (the host) and an eubacterium (the symbiont) that is able to respire, but which generates molecular hydrogen as an end product of anaerobic metabolism. The resulting proto-eukaryotic cell would have acquired the essentials of eukaryotic energy metabolism, evolving not only aerobic respiration, but also the cost of oxygen consumption, i.e., generation of reactive oxygen species (ROS) and oxidative damage. Mitochondria contain their own genome with a modified genetic code that is highly conserved among mammals. Control of gene expression suggests that transcription of certain mitochondrial genes may be regulated in response to the redox potential of the mitochondrial membrane. Mitochondria are involved in energy production and conservation, and they have an uncoupling mechanism to produce heat instead of ATP. Also, mitochondria are involved in programmed cell death. Increasing evidence suggests the participation of mitochondria in neurodegenerative and neuromuscular diseases involving alterations in both nuclear (nDNA) and mitochondrial (mtDNA) DNA. Melatonin is now known as a powerful antioxidant and increasing experimental evidence shows its beneficial effects against oxidative stress-induced macromolecular damage and diseases, including those in which mitochondrial function is affected. This review summarizes the data and mechanisms of action of melatonin in relation to mitochondrial pathologies.", "conclusion": "Melatonin is now known as a powerful antioxidant and increasing experimental evidence shows its beneficial effects against oxidative stress-induced macromolecular damage and diseases, including those in which mitochondrial function is affected. This review summarizes the data and mechanisms of action of melatonin in relation to mitochondrial pathologies." }, { "pmid": "12228253", "year": 2002, "title": "Crystal structure of human sex hormone-binding globulin in complex with 2-methoxyestradiol reveals the molecular basis for high affinity interactions with C-2 derivatives of estradiol.", "title_en": null, "title_de": "Kristallstruktur des humanen sexualhormonbindenden Globulins im Komplex mit 2-Methoxyestradiol offenbart die molekulare Grundlage für hochaffine Interaktionen mit C-2-Derivaten von Estradiol", "journal": "The Journal of biological chemistry", "authors": "Avvakumov et al.", "author_search": "avvakumov avvakumov", "doi": "10.1074/jbc.m207762200", "doi_url": "https://doi.org/10.1074/jbc.m207762200", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/12228253/", "url": "https://h2medicine.org/studies/study-avvakumov-2002-crystal-structure-sex-hormone/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2002 · Avvakumov et al. — Crystal structure of human sex hormone-binding globulin in complex with 2-methoxyestradiol reveals the molecular basis for high affinity interactions with C-2 derivatives of estradiol", "summary": "This in-vitro structural biology study resolves the crystal structure of human sex hormone-binding globulin (SHBG) bound to 2-methoxyestradiol, explaining at the atomic level why certain estradiol derivatives bind with high or low affinity. Molecular hydrogen (H₂) appears only as a structural chemistry term (hydrogen bonding between amino acid residues and the steroid). This has no connection to H₂ supplementation or any H₂ health application.", "assessment": "A structural biology / crystallography study describing protein-ligand interactions involving hydrogen bonds in the chemical sense. This paper has absolutely no connection to molecular hydrogen (H₂) as a health or supplementation agent. The word „hydrogen” in the abstract refers to hydrogen bonds — a routine structural chemistry term — not dissolved H₂ gas.", "abstract": "In a crystal structure of the amino-terminal laminin G-like domain of human sex hormone-binding globulin (SHBG), the biologically active estrogen metabolite, 2-methoxyestradiol (2-MeOE2), binds in the same orientation as estradiol. The high affinity of SHBG for 2-MeOE2 relies primarily on hydrogen bonding between the hydroxyl at C-3 of 2-MeOE2 and Asp(65) and an interaction between the methoxy group at C-2 and the amido group of Asn(82). Accommodation of the 2-MeOE2 methoxy group causes an outward displacement of residues Ser(128)-Pro(130), which appears to disorder and displace the loop region (Leu(131)-His(136)) that covers the steroid-binding site. This could influence the binding kinetics of 2-MeOE2 and/or facilitate ligand-dependent interactions between SHBG and other proteins. Occupancy of a zinc-binding site reduces the affinity of SHBG for 2-MeOE2 and estradiol in the same way. The higher affinity of SHBG for estradiol derivatives with a halogen atom at C-2 is due to either enhanced hydrogen bonding between the hydroxyl at C-3 and Asp(65) (2-fluoroestradiol) or accommodation of the functional group at C-2 (2-bromoestradiol), rather than an interaction with Asn(82). By contrast, the low affinity of SHBG for 2-hydroxyestradiol can be attributed to intra-molecular hydrogen bonding between the hydroxyls in the aromatic steroid ring A, which generates a steric clash with the amido group of Asn(82). Understanding how C-2 derivatives of estradiol interact with SHBG could facilitate the design of biologically active synthetic estrogens.", "conclusion": "By contrast, the low affinity of SHBG for 2-hydroxyestradiol can be attributed to intra-molecular hydrogen bonding between the hydroxyls in the aromatic steroid ring A, which generates a steric clash with the amido group of Asn(82). Understanding how C-2 derivatives of estradiol interact with SHBG could facilitate the design of biologically active synthetic estrogens." }, { "pmid": "12049920", "year": 2002, "title": "Hydrogenases in green algae: do they save the algae's life and solve our energy problems?", "title_en": null, "title_de": "Hydrogenasen in Grünalgen: Retten sie das Leben der Algen und lösen sie unsere Energieprobleme?", "journal": "Trends in plant science", "authors": "Happe et al.", "author_search": "happe happe", "doi": "10.1016/s1360-1385(02)02274-4", "doi_url": "https://doi.org/10.1016/s1360-1385(02)02274-4", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/12049920/", "url": "https://h2medicine.org/studies/study-happe-2002-hydrogenases-green-algae-they/", "methods": [ "inhalation" ], "indications": [ "sports-exercise", "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2002 · Happe — Hydrogenases in green algae: do they save the algae's life and solve our energy problems?", "summary": "Green algae are the only known eukaryotes capable of both photosynthesis and hydrogen metabolism — a dual ability that may hold the key to sustainable H₂ production. This in-vitro study shows that the enzyme [Fe]-hydrogenase acts as an electron „valve,“ allowing algae to survive anaerobic conditions. Under sulfur deprivation, algae can produce large quantities of hydrogen gas — a finding with potential relevance for future energy technology. (Trends in Plant Science, 2002.)", "assessment": "This is a basic science paper on algal hydrogen metabolism — it is not a therapeutic study and contains no data on hydrogen effects in animals or humans. The relevance to H₂ medicine is indirect at best: the work helps explain where biological H₂ comes from and how hydrogenases work at a molecular level. The idea of using algae for large-scale H₂ production has since been explored further, though commercial viability remains an open challenge. Readers interested in H₂ therapy should note that this study provides no evidence for health effects of hydrogen in humans.", "abstract": "Green algae are the only known eukaryotes with both oxygenic photosynthesis and a hydrogen metabolism. Recent physiological and genetic discoveries indicate a close connection between these metabolic pathways. The anaerobically inducible hydA genes of algae encode a special type of highly active [Fe]-hydrogenase. Electrons from reducing equivalents generated during fermentation enter the photosynthetic electron transport chain via the plastoquinone pool. They are transferred to the hydrogenase by photosystem I and ferredoxin. Thus, the [Fe]-hydrogenase is an electron 'valve' that enables the algae to survive under anaerobic conditions. During sulfur deprivation, illuminated algal cultures evolve large quantities of hydrogen gas, and this promises to be an alternative future energy source.", "conclusion": "Thus, the [Fe]-hydrogenase is an electron 'valve' that enables the algae to survive under anaerobic conditions. During sulfur deprivation, illuminated algal cultures evolve large quantities of hydrogen gas, and this promises to be an alternative future energy source." }, { "pmid": "11847105", "year": 2002, "title": "Conserved properties of hydrogenosomal and mitochondrial ADP/ATP carriers: a common origin for both organelles.", "title_en": null, "title_de": "Konservierte Eigenschaften hydrogenosomaler und mitochondrialer ADP/ATP-Carrier: ein gemeinsamer Ursprung für beide Organellen.", "journal": "The EMBO journal", "authors": "van der Giezen et al.", "author_search": "van der giezen van der giezen", "doi": "10.1093/emboj/21.4.572", "doi_url": "https://doi.org/10.1093/emboj/21.4.572", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/11847105/", "url": "https://h2medicine.org/studies/study-vandergiezen-2002-conserved-properties-hydrogenosomal-mitochondrial/", "methods": [ "unspecified" ], "indications": [ "sports-exercise" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2002 · van der Giezen — Conserved properties of hydrogenosomal and mitochondrial ADP/ATP carriers: a common origin for both organelles.", "summary": "Hydrogenosomes — the hydrogen-producing organelles found in certain anaerobic eukaryotes — and mitochondria share the same fundamental ADP/ATP transport machinery, providing strong evidence that both organelles descend from a common ancestor. This in-vitro study demonstrates that the hydrogenosomal ADP/ATP carrier from the anaerobic fungus Neocallimastix can functionally substitute for its mitochondrial counterpart in yeast. (The EMBO Journal, 2002.)", "assessment": "This is a basic science paper in evolutionary cell biology — it is not a therapeutic study and provides no evidence for health effects of hydrogen in humans. Its relevance to H₂ medicine is limited to the biological context: it explains the cellular machinery by which some organisms produce molecular hydrogen naturally. The work is methodologically rigorous and was influential in establishing the mitochondrial origin of hydrogenosomes. Readers interested in H₂ therapy will find no clinically applicable findings here.", "abstract": "Mitochondria are one of the hallmarks of eukaryotic cells, exporting ATP in exchange for cytosolic ADP using ADP/ATP carriers (AAC) located in the inner mitochondrial membrane. In contrast, several evolutionarily important anaerobic eukaryotes lack mitochondria but contain hydrogenosomes, peculiar organelles of controversial ancestry that also supply ATP but, like some fermentative bacteria, make molecular hydrogen in the process. We have now identified genes from two species of the hydrogenosome-containing fungus Neocallimastix that have three-fold sequence repeats and signature motifs that, along with phylogenetic analysis, identify them as AACs. When expressed in a mitochondrial AAC- deficient yeast strain, the hydrogenosomal protein was correctly targeted to the yeast mitochondria inner membrane and yielded mitochondria able to perform ADP/ATP exchange. Characteristic inhibitors of mitochondrial AACs blocked adenine nucleotide exchange by the Neocallimastix protein. Thus, our data demonstrate that fungal hydrogenosomes and yeast mitochondria use the same pathway for ADP/ATP exchange. These experiments provide some of the strongest evidence yet that yeast mitochondria and Neocallimastix hydrogenosomes are but two manifestations of the same fundamental organelle.", "conclusion": "Thus, our data demonstrate that fungal hydrogenosomes and yeast mitochondria use the same pathway for ADP/ATP exchange. These experiments provide some of the strongest evidence yet that yeast mitochondria and Neocallimastix hydrogenosomes are but two manifestations of the same fundamental organelle." }, { "pmid": "11797894", "year": 2002, "title": "Tritium doses from chronic atmospheric releases: a new approach proposed for regulatory compliance.", "title_en": null, "title_de": "Tritium-Dosen aus chronischen atmosphärischen Freisetzungen: ein neuer Ansatz zur Einhaltung regulatorischer Vorgaben.", "journal": "Health physics", "authors": "Peterson et al.", "author_search": "peterson peterson", "doi": "10.1097/00004032-200202000-00006", "doi_url": "https://doi.org/10.1097/00004032-200202000-00006", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/11797894/", "url": "https://h2medicine.org/studies/study-peterson-2002-tritium-doses-chronic-atmospheric/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2002 · Peterson — Tritium doses from chronic atmospheric releases: a new approach proposed for regulatory compliance.", "summary": "This theoretical modelling study proposes an improved regulatory model (NEWTRIT) for calculating human doses from atmospheric tritium releases — including tritiated hydrogen gas (HT) and organically bound tritium in food. The new model accounts for all exposure pathways and gives more comprehensive, scientifically defensible dose estimates than existing regulatory frameworks. (Health Physics, 2002.)", "assessment": "This is a theoretical radiation-protection study — it is entirely unrelated to therapeutic or health-promoting effects of molecular hydrogen (H₂). The „hydrogen“ in this paper refers to radioactive tritium (³H) in the context of nuclear emissions regulation. There are no findings applicable to H₂ medicine, H₂ water, or H₂ inhalation therapy. The study is methodologically sound within its domain (dosimetry modelling) and the proposed NEWTRIT framework is a genuine improvement for regulatory science. Readers searching for clinical H₂ evidence will find nothing relevant here.", "abstract": "Regulatory models for atmospheric releases of tritium approved by the Environmental Protection Agency (CAP88, AIRDOS-PC, and COMPLY) calculate doses only from tritiated water (HTO) taken into the body. They do not deal with dose from emissions of tritiated hydrogen gas (HT) and conversion of HT to HTO in the environment, nor do they address the dose from ingesting tritium incorporated into organic compounds. A simple model (NEWTRIT) is proposed that accounts for all pathways to dose from atmospheric releases of HT and HTO. The model is formulated in terms of the tritium-to-hydrogen ratio in each environmental compartment. With each transfer, a small reduction in the ratio is introduced to reflect the dilution that occurs in nature. Conversion of HT to HTO in the environment is modeled using the latest experimental data. Concentrations of organically bound tritium are calculated in foodstuffs based on amounts of hydrogen in proteins, fats, and carbohydrates. Concentrations in foodstuffs and doses calculated by NEWTRIT are consistent with the predictions of existing regulatory models. In addition, the HTO component of NEWTRIT is tested using public bioassay data and the HT component is tested using results from a model intercomparison study for a hypothetical HT release. Although tritium doses probably have not been underestimated by regulatory models that account only for HTO (due to the high degree of conservatism built into these models), the explicit treatment of HT and organically bound tritium proposed here will make the dose assessments more comprehensive, defensible, and scientifically acceptable. Because NEWTRIT includes all pathways to dose and predicts conservative doses, it is a suitable model to replace the tritium models currently used for compliance.", "conclusion": "Although tritium doses probably have not been underestimated by regulatory models that account only for HTO (due to the high degree of conservatism built into these models), the explicit treatment of HT and organically bound tritium proposed here will make the dose assessments more comprehensive, defensible, and scientifically acceptable. Because NEWTRIT includes all pathways to dose and predicts " }, { "pmid": "11713968", "year": 2001, "title": "Lactulose-induced pneumatosis intestinalis and pneumoperitoneum.", "title_en": null, "title_de": "Lactulose-induzierte Pneumatosis intestinalis und Pneumoperitoneum.", "journal": "Digestive diseases and sciences", "authors": "Goodman et al.", "author_search": "goodman goodman", "doi": "10.1023/a:1012308911096", "doi_url": "https://doi.org/10.1023/a:1012308911096", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/11713968/", "url": "https://h2medicine.org/studies/study-goodman-2001-lactulose-induced-pneumatosis-intestinalis/", "methods": [], "indications": [ "other" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "byproduct", "headline": "2001 · Goodman — Lactulose-induced pneumatosis intestinalis and pneumoperitoneum.", "summary": "A 57-year-old patient with colonic inertia developed pneumatosis intestinalis and pneumoperitoneum after lactulose treatment, caused by a build-up of carbon dioxide and hydrogen gas from bacterial fermentation in a setting of altered gut flora. H₂ here is an endogenous gas produced by abnormal fermentation — not a therapeutic agent. (Digestive Diseases and Sciences, 2001.)", "assessment": "Assessment note: This study is not an H₂ therapy trial. It is a case report of a complication in which endogenously produced hydrogen and CO₂ accumulated to pathological levels. This is in fact an example of H₂ causing harm (through pressure-induced pneumatosis) rather than providing therapeutic benefit. No molecular hydrogen was administered. The study is not appropriate for inclusion in an H₂ therapy database without an explicit disclaimer.", "abstract": "A case of PI in a 57-year-old patient with colonic inertia treated with lactulose for PSE secondary to cirrhosis is described. The colonic inertia led to longer transit time. Retained lactulose and a build-up of carbon dioxide and hydrogen gas occurred in the setting of altered bacterial flora deficient in hydrogen metabolism. The increased gas pressure caused extravasation of air into the intestine, causing PI with pneumoperitoneum. They both resolved with discontinuation of lactulose.", "conclusion": "The increased gas pressure caused extravasation of air into the intestine, causing PI with pneumoperitoneum. They both resolved with discontinuation of lactulose." }, { "pmid": "11293569", "year": 2001, "title": "Hydrogenosome morphological variation induced by fibronectin and other drugs in Trichomonas vaginalis and Tritrichomonas foetus.", "title_en": null, "title_de": "Morphologische Variation der Hydrogenosomen induziert durch Fibronektin und andere Wirkstoffe bei Trichomonas vaginalis und Tritrichomonas foetus.", "journal": "Parasitology research", "authors": "Benchimol", "author_search": "benchimol benchimol", "doi": "10.1007/s004360000329", "doi_url": "https://doi.org/10.1007/s004360000329", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/11293569/", "url": "https://h2medicine.org/studies/study-benchimol-2001-hydrogenosome-morphological-variation-induced/", "methods": [ "unspecified" ], "indications": [ "sports-exercise" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2001 · Benchimol — Hydrogenosome morphological variation induced by fibronectin and other drugs in Trichomonas vaginalis and Tritrichomonas foetus.", "summary": "Hydrogenosomes — organelles in anaerobic protozoa that produce molecular hydrogen — show remarkable morphological plasticity when exposed to fibronectin, hydroxyurea, or cytochalasin B. This in-vitro study in the parasitic protozoa Trichomonas vaginalis and Tritrichomonas foetus reveals that hydrogenosomes can dramatically alter their size and shape in response to stress, suggesting a compensatory adaptation mechanism. (Parasitology Research, 2001.)", "assessment": "This is a basic cell biology study on parasitic protozoa — it is not a therapeutic study and contains no findings relevant to human health or H₂ medicine. The „hydrogen“ connection is purely biological: these parasites happen to produce H₂ in their hydrogenosomes. The study is methodologically sound ultrastructural work. Readers interested in the therapeutic effects of molecular hydrogen in humans will find no clinically applicable information here.", "abstract": "The hydrogenosome is a spherical organelle, found in some anaerobic protozoa, which participates in ATP and molecular hydrogen formation. The morphological alterations in hydrogenosomes induced by fibronectin, hydroxyurea and cytochalasin B in Trichomonas vaginalis and Tritrichomonas foetus are presented. We demonstrate that, under experimental conditions, the hydrogenosome presents a high diversity in size and shape, suggesting a mechanism that seems to compensate for the stress provoked by drugs. The following experimental procedures were used: (1) fibronectin-mediated endocytic activity, (2) 4 mM hydroxyurea for 15 h, and (3) 10 microg cytochalasin B/ml in the culture medium. The main alterations observed in hydrogenosomes were: (1) formation of giant hydrogenosomes, (2) presence of internal membranes, (3) increased diversity of non-spherical forms, some of them bizarre, (4) presence of sub-compartments in the matrix, as vesicles, (5) presence of ribosome-like particles on the outer hydrogenosomal membrane, (6) enlargement of the peripheral vesicle, and (7) continuity with membrane profiles.", "conclusion": "The following experimental procedures were used: (1) fibronectin-mediated endocytic activity, (2) 4 mM hydroxyurea for 15 h, and (3) 10 microg cytochalasin B/ml in the culture medium. The main alterations observed in hydrogenosomes were: (1) formation of giant hydrogenosomes, (2) presence of internal membranes, (3) increased diversity of non-spherical forms, some of them bizarre, (4) presence of s" }, { "pmid": "10944388", "year": 2000, "title": "Crystal structure of bovine duodenase, a serine protease, with dual trypsin and chymotrypsin-like specificities.", "title_en": null, "title_de": "Kristallstruktur der bovinen Duodenase, einer Serinprotease, mit dualer trypsin- und chymotrypsinähnlicher Spezifität.", "journal": "Proteins", "authors": "Pletnev et al.", "author_search": "pletnev pletnev", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/10944388/", "url": "https://h2medicine.org/studies/study-pletnev-2000-crystal-structure-bovine-duodenase/", "methods": [ "drinking-hrw" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "2000 · Pletnev — Crystal structure of bovine duodenase, a serine protease, with dual trypsin and chymotrypsin-like specificities.", "summary": "This in-vitro structural study resolves the three-dimensional crystal structure of duodenase, a serine protease from bovine duodenum, at 2.4 Å resolution. The enzyme can cleave both trypsin-type and chymotrypsin-type substrates — a specificity long thought impossible — and its active site contains a hydrogen water network that may be key to its catalytic mechanism. (Proteins, 2000.)", "assessment": "This is a basic structural biochemistry study — it has no relevance to molecular H₂ therapy. The „hydrogen“ in this paper refers exclusively to hydrogen bonds and water molecules in the enzyme active site. The study is of interest for enzymology and structural biology but provides no evidence for health effects of H₂ in any model. The inclusion in a hydrogen-related database appears to be based on keyword overlap rather than biological relevance.", "abstract": "The three-dimensional structure of duodenase, a serine protease from bovine duodenum mucosa, has been determined at 2.4A resolution. The enzyme, which has both trypsin-like and chymotrypsin-like activities, most closely resembles human cathepsin G with which it shares 57% sequence identity and similar specificity. The catalytic Ser195 in duodenase adopts the energetically favored conformation typical of serine proteinases and unlike the strained state typical of lipase/esterases. Of several waters in the active site of duodenase, the one associated with Ser214 is found in all serine proteinases and most lipase/esterases. The conservation of the Ser214 residue in serine proteinase, its presence in the active site, and participation in a hydrogen water network involving the catalytic triad (His57, Asp107, and Ser195) argues for its having an important role in the mechanism of action. It may be referred to as a fourth member of the catalytic triad. Duodenase is one of a growing family of enzymes that possesses trypsin-like and chymotrypsin-like activity. Not long ago, these activities were considered to be mutually exclusive. Computer modeling reveals that the S1 subsite of duodenase has structural features compatible with effective accommodation of P1 residues typical of trypsin (Arg/Lys) and chymotrypsin (Tyr/Phe) substrates. The determination of structural features associated with functional variation in the enzyme family may permit design of enzymes with a specific ratio of trypsin and chymotrypsin activities.", "conclusion": "Computer modeling reveals that the S1 subsite of duodenase has structural features compatible with effective accommodation of P1 residues typical of trypsin (Arg/Lys) and chymotrypsin (Tyr/Phe) substrates. The determination of structural features associated with functional variation in the enzyme family may permit design of enzymes with a specific ratio of trypsin and chymotrypsin activities." }, { "pmid": "10812376", "year": 2000, "title": "Improved lactose digestion and intolerance among African-American adolescent girls fed a dairy-rich diet.", "title_en": null, "title_de": "Verbesserte Lactoseverdauung und -intoleranz bei afroamerikanischen heranwachsenden Mädchen unter milchreicher Ernährung.", "journal": "Journal of the American Dietetic Association", "authors": "Pribila et al.", "author_search": "pribila pribila", "doi": "10.1016/s0002-8223(00)00162-0", "doi_url": "https://doi.org/10.1016/s0002-8223(00)00162-0", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/10812376/", "url": "https://h2medicine.org/studies/study-pribila-2000-improved-lactose-digestion-intolerance/", "methods": [], "indications": [ "skin-aging" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "breath-test", "headline": "2000 · Pribila — Improved lactose digestion and intolerance among African-American adolescent girls fed a dairy-rich diet.", "summary": "After 21 days on a dairy-rich diet, African-American adolescent girls with lactose maldigestion showed significantly reduced breath hydrogen excretion and negligible gastrointestinal symptoms, suggesting colonic adaptation to lactose. Breath H₂ serves here as a diagnostic marker, not as a therapeutic agent. (Journal of the American Dietetic Association, 2000.)", "assessment": "Assessment note: This study is not an H₂ therapy trial. H₂ is measured as a breath biomarker of gut fermentation/malabsorption — it is not administered to subjects. The dietary intervention is a high-lactose diet, and H₂ measurement is the outcome measure for assessing colonic fermentation. This is a nutritional and gut-physiology study. No therapeutic H₂ endpoints. Should not be presented in an H₂ therapy context.", "abstract": "OBJECTIVE: To determine whether African-American adolescent girls who were fed a dairy-rich diet for 21 days could adapt to lactose, experiencing an overall improvement in lactose tolerance as well as a decrease in hydrogen gas production. DESIGN: Twenty-one-day dietary intervention study. SUBJECTS/SETTING: Seventeen of 21 African-American girls (aged 11 to 15 years) enrolled in a calcium metabolism study chose to participate in the lactose tolerance study. Subjects were screened for any diseases, conditions, or medications that might alter calcium metabolism or colonic fermentation. Subjects were housed in a fraternity on the Purdue University, West Lafayette, Ind, campus, and were supervised 24 hours a day. INTERVENTION: Subjects consumed a dairy-based diet averaging 1,200 mg calcium and 33 g lactose per day for 21 days. Lactose digestion was assessed by an 8-hour breath hydrogen test on days 1 and 21, and symptoms of intolerance (abdominal pain, bloating, flatulence, and diarrhea) were evaluated hourly on a ranked scale during the breath hydrogen tests and once each evening during the 21-day feeding period. MAIN OUTCOME MEASURES: A comparison of breath hydrogen production and gastrointestinal symptoms at the beginning and end of the study. STATISTICAL ANALYSES PERFORMED: The Wilcoxon signed ranks test was used to compare the area under the curve for the 2 breath hydrogen tests. Spearman's p test for trend was used to determine whether there was a change in symptoms. All statistical analyses were 2-tailed and significance was set at P = .05. RESULTS: Fourteen of the 17 subjects had lactose maldigestion. Breath hydrogen excretion decreased significantly (P < .03) from the beginning (148.3 +/- 27.0 ppm x hours) to the end (100.7 +/- 19.3 ppm x hours) of the 21-day period. Gastrointestinal symptoms were negligible during both the breath hydrogen tests as were symptoms during the 21-day period. APPLICATIONS/CONCLUSIONS: The diet was well tolerated by the subjects. Furthermore, the decrease in breath hydrogen suggests colonic adaptation to the high-lactose diet. The results indicate that lactose maldigestion should not be a restricting factor in developing adequate calcium diets for this population. The existence of lactose maldigestion does not result in lactose intolerance in this population when it is fed a dairy-rich diet.", "conclusion": "The diet was well tolerated by the subjects. Furthermore, the decrease in breath hydrogen suggests colonic adaptation to the high-lactose diet. The results indicate that lactose maldigestion should not be a restricting factor in developing adequate calcium diets for this population. The existence of lactose maldigestion does not result in lactose intolerance in this population when it is fed a dairy-rich diet." }, { "pmid": "10650267", "year": 2000, "title": "Endoscopic measurement of pancreatic tissue perfusion in patients with chronic pancreatitis and control patients.", "title_en": null, "title_de": "Endoskopische Messung der pankreatischen Gewebeperfusion bei Patienten mit chronischer Pankreatitis und Kontrollpatienten.", "journal": "Gastrointestinal endoscopy", "authors": "Lewis et al.", "author_search": "lewis lewis", "doi": "10.1016/s0016-5107(00)70417-2", "doi_url": "https://doi.org/10.1016/s0016-5107(00)70417-2", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/10650267/", "url": "https://h2medicine.org/studies/study-lewis-2000-endoscopic-measurement-pancreatic-tissue/", "methods": [], "indications": [ "cardiovascular" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "tracer-clearance", "headline": "2000 · Lewis — Endoscopic measurement of pancreatic tissue perfusion in patients with chronic pancreatitis and control patients.", "summary": "Pancreatic blood flow was measured endoscopically using the hydrogen gas clearance technique in patients with chronic pancreatitis, revealing significantly lower perfusion compared to controls. H₂ here is an inert diagnostic gas used to measure tissue perfusion — not a therapeutic agent. (Gastrointestinal Endoscopy, 2000.)", "assessment": "Assessment note: This study is not an H₂ therapy trial. H₂ is used as an inert tracer gas for measuring tissue perfusion via the clearance technique. No H₂ was administered for therapeutic purposes. This is a diagnostic physiology study in chronic pancreatitis. No therapeutic claims regarding H₂ can be derived from this work. It should not appear in an H₂ therapy database without a clear disclaimer.", "abstract": "BACKGROUND: Pancreatic blood flow is diminished in experimental models of acute and chronic pancreatitis. We attempted to develop a safe and reliable technique for its measurement in patients and to examine blood flow in patients with chronic pancreatitis and in control subjects. METHOD: Pancreatic blood flow was measured using the hydrogen gas clearance technique and an endoscopically placed platinum ductal electrode. Pancreatic blood flow was measured in 12 patients with chronic pancreatitis diagnosed clinically and radiographically, and in 11 control patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) for non-pancreatic pathology. RESULTS: Patients with chronic pancreatitis had a significantly lower pancreatic blood flow compared with control patients (51.5 versus 91.7 mL/min/100 gm, p < 0.01). With secretin stimulation pancreatic blood flow increased in two control patients, whereas this notable rise was not seen in three patients with chronic pancreatitis. CONCLUSIONS: Measurement of pancreatic blood flow with an endoscopically placed electrode is relatively safe and simple to perform. The scarring and vascular fibrosis associated histologically with chronic pancreatitis is reflected in lower pancreatic blood flow.", "conclusion": "Measurement of pancreatic blood flow with an endoscopically placed electrode is relatively safe and simple to perform. The scarring and vascular fibrosis associated histologically with chronic pancreatitis is reflected in lower pancreatic blood flow." }, { "pmid": "10193122", "year": 1999, "title": "[Lactose intolerance in children. An analysis of hydrogen gas in exhaled air simplifies and improves diagnosis].", "title_en": null, "title_de": "Lactoseintoleranz bei Kindern. Eine Analyse von Wasserstoffgas in der Ausatemluft vereinfacht und verbessert die Diagnose.", "journal": "Lakartidningen", "authors": "Särnblad et al.", "author_search": "särnblad särnblad", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/10193122/", "url": "https://h2medicine.org/studies/study-saernblad-1999-lactose-intolerance-children-analysis/", "methods": [ "inhalation" ], "indications": [ "other" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "1999 · Särnblad — Lactose intolerance in children. An analysis of hydrogen gas in exhaled air simplifies and improves diagnosis.", "summary": "This review article, published in the Swedish medical journal Läkartidningen, discusses the hydrogen breath test as a diagnostic tool for lactose intolerance in children. The exhaled hydrogen gas method is presented as a simpler and more reliable alternative for diagnosing lactose malabsorption. No abstract is available in the indexed record. (Läkartidningen, 1999.)", "assessment": "This is a review article on clinical diagnostics — specifically the hydrogen breath test for lactose intolerance in children. The „hydrogen“ is a diagnostic marker (produced by gut bacteria), not a therapeutic agent. No abstract is available; content cannot be fully assessed. The article is in Swedish with no English translation on record. This paper is not relevant to H₂ therapy or supplementation.", "abstract": null, "conclusion": null }, { "pmid": "10520620", "year": 1999, "title": "Consequences of incomplete carbohydrate absorption from fruit juice consumption in infants.", "title_en": null, "title_de": "Folgen der unvollständigen Kohlenhydratabsorption beim Konsum von Fruchtsaft bei Säuglingen.", "journal": "Archives of pediatrics & adolescent medicine", "authors": "Cole et al.", "author_search": "cole cole", "doi": "10.1001/archpedi.153.10.1098", "doi_url": "https://doi.org/10.1001/archpedi.153.10.1098", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/10520620/", "url": "https://h2medicine.org/studies/study-cole-1999-consequences-incomplete-carbohydrate-absorption/", "methods": [], "indications": [ "sports-exercise", "respiratory" ], "evidence_level": 3, "human": true, "therapeutic": false, "h2category": "breath-test", "headline": "1999 · Cole — Consequences of incomplete carbohydrate absorption from fruit juice consumption in infants.", "summary": "In healthy infants aged ~5 months, consumption of pear juice (containing sorbitol and high fructose) caused carbohydrate malabsorption detectable by breath hydrogen testing, and was associated with increased physical activity and metabolic rate compared to infants who absorbed the carbohydrates normally. H₂ is a breath biomarker here, not a therapeutic agent. (Archives of Pediatrics & Adolescent Medicine, 1999.)", "assessment": "Assessment note: This study is not an H₂ therapy trial. Breath H₂ is used as a diagnostic marker of gut carbohydrate malabsorption in infants. No hydrogen was administered therapeutically. This is a pediatric nutrition/GI physiology study. No therapeutic claims regarding H₂ are applicable. It should not appear in an H₂ therapy database without a clear disclaimer.", "abstract": "BACKGROUND: Most infants consume fruit juices by 6 months of age. However, fruit juices containing sorbitol may be associated with carbohydrate malabsorption without clinical symptoms. We hypothesized that increased physical activity and metabolic rate may be associated with carbohydrate malabsorption. METHODS: Physical activity and metabolic rate were determined in 14 healthy infants ([mean +/- SD] age, 5.1 +/- 0.8 months; weight, 7.8 +/- 1.1 kg; length, 67 +/- 4.2 cm; and body fat, 26% +/- 5%) for 3 hours in a respiratory chamber. Seven were fed pear juice, and the other 7 were fed white grape juice (120 mL) after a 2-hour fast. Pear juice contains sorbitol and a high fructose-glucose ratio, whereas white grape juice is sorbitol free and has a low fructose-glucose ratio. Carbohydrate absorption was determined by breath hydrogen gas analysis. The study was double-blinded. RESULTS: When compared with the infants without carbohydrate malabsorption (peak breath hydrogen level < 20 ppm above baseline), 5 of the 7 infants fed pear juice and 2 of the 7 infants fed white grape juice exhibited carbohydrate malabsorption (peak breath hydrogen level > or = 20 ppm above baseline; P < .01). These infants also exhibited both increased physical activity (P < .001) and metabolic rate (P < .05) after juice consumption in comparison with infants with normal carbohydrate absorption. When grouped according to the type of juice consumed, only infants fed pear juice exhibited increases in physical activity (P < .01). CONCLUSIONS: Carbohydrate malabsorption is associated with increased physical activity and metabolic rate in infants. Most of the infants who had carbohydrate malabsorption consumed pear juice. Therefore, fruit juices containing sorbitol and high levels of fructose may not be optimal for young infants.", "conclusion": "Carbohydrate malabsorption is associated with increased physical activity and metabolic rate in infants. Most of the infants who had carbohydrate malabsorption consumed pear juice. Therefore, fruit juices containing sorbitol and high levels of fructose may not be optimal for young infants." }, { "pmid": "10659209", "year": 1999, "title": "Oxygen and hydrogen gas transport through living C6 cell suspensions is faster than that in dead cells.", "title_en": null, "title_de": "Der Transport von Sauerstoff- und Wasserstoffgas durch lebende C6-Zellsuspensionen ist schneller als der in toten Zellen.", "journal": "Advances in experimental medicine and biology", "authors": "Tomita et al.", "author_search": "tomita tomita", "doi": "10.1007/978-1-4615-4717-4_85", "doi_url": "https://doi.org/10.1007/978-1-4615-4717-4_85", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/10659209/", "url": "https://h2medicine.org/studies/study-tomita-1999-oxygen-transport-through-living/", "methods": [ "inhalation" ], "indications": [ "sports-exercise" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "1999 · Tomita — Oxygen and hydrogen gas transport through living C6 cell suspensions is faster than that in dead cells.", "summary": "This in-vitro study demonstrates that living C6 (rat glioma) cell suspensions transport both oxygen and molecular hydrogen gas more rapidly than dead cell suspensions. The finding suggests that active biological processes in living cells facilitate gas diffusion, which has implications for understanding how dissolved H₂ moves through biological tissues. (Advances in Experimental Medicine and Biology, 1999.)", "assessment": "This is a basic in-vitro biophysics study on gas transport in cell suspensions — it is not a therapeutic study. The finding that living cells facilitate H₂ transport faster than dead cells is mechanistically interesting for understanding H₂ bioavailability, but the paper provides no evidence for clinical effects of H₂ in any therapeutic context. No abstract is available in the database record; detailed assessment requires the original publication (DOI: 10.1007/978-1-4615-4717-4_85).", "abstract": null, "conclusion": null }, { "pmid": "10550517", "year": 1999, "title": "A preventive effect of a selective endothelin-A receptor antagonist, S-0139, on the erythropoietin-induced reduction of the renal cortical blood flow.", "title_en": null, "title_de": "Eine präventive Wirkung eines selektiven Endothelin-A-Rezeptor-Antagonisten, S-0139, auf die erythropoetininduzierte Verminderung des renalen kortikalen Blutflusses.", "journal": "Urological research", "authors": "Ishikawa et al.", "author_search": "ishikawa ishikawa", "doi": "10.1007/s002400050156", "doi_url": "https://doi.org/10.1007/s002400050156", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/10550517/", "url": "https://h2medicine.org/studies/study-ishikawa-1999-preventive-selective-endothelin-receptor/", "methods": [ "inhalation", "saline-iv", "drinking-hrw" ], "indications": [ "metabolic", "cardiovascular", "kidney-dialysis" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "1999 · Ishikawa — A preventive effect of a selective endothelin-A receptor antagonist, S-0139, on the erythropoietin-induced reduction of the renal cortical blood flow.", "summary": "This animal study in Wistar rats shows that erythropoietin (EPO) reduces renal cortical blood flow (RCBF) by triggering endothelin-1 release, and that the selective ET-A receptor antagonist S-0139 can prevent this reduction. Molecular hydrogen gas was used purely as a measurement tool (hydrogen gas clearance method), not as a therapeutic intervention. (Urological Research, 1999.)", "assessment": "This is an animal pharmacology study (rat model) — it is not a therapeutic H₂ study. Molecular hydrogen was used exclusively as a measurement tool (clearance method) to quantify renal blood flow. The therapeutic subject is endothelin-A receptor antagonism, not H₂. Results cannot be extrapolated to humans without further clinical validation. The renal blood flow finding is of interest for nephrology and EPO therapy management, but provides no evidence for H₂ health effects.", "abstract": "We have confirmed that renal cortical blood flow (RCBF) is significantly decreased by recombinant human erythropoietin (EPO). Endothelin-1 (ET(1)) is thought to be a mediator because its level increased significantly when EPO was administered. The present study was performed to clarify the effect of a selective ET-A receptor antagonist, S-0139, on EPO-induced RCBF reduction. Ten-week-old male Wistar rats, weighing about 250 g, were divided into five groups. Group 1 (n = 5), a control group, received normal saline solution (NSS). Group 2 (n = 5) received 200 U/kg body weight (BW) per hour of EPO. Group 3 (n = 5) received 400 U/kg BW per hour of EPO. Group 4 (n = 5) received both 200 U/kg BW per hour of EPO and 4 mg/kg BW per hour of S-0139. Group 5 (n = 5) received both 200 U/kg BW per hour of EPO and 40 mg/kg BW per hour of S-0139. Drugs were administered intravenously via the right femoral vein using a microinfusion pump for 4 h under urethane anesthesia. The RCBF was measured every 30 min by the hydrogen gas clearance method. When the 4 h had elapsed, the concentrations of plasma creatinine (Cr), ET1 and renin activity (RA) were measured. Compared with group 1, groups 2 and 3 showed significant (P < 0.001) decreases of RCBF, while the ET1 levels of these two groups increased significantly (P < 0.03). The ET1 of groups 4 and 5 also increased significantly (P < 0.03), however, the RCBF of these two groups did not decrease. No significant differences were observed in either Cr or RA between the five groups. EPO induces ET(1) secretion. The reduction of RCBF is due to ET(1)-derived vasoconstriction. S-0139 has potential for preventing EPO-induced and ET(1)-mediated RCBF reduction.", "conclusion": "The reduction of RCBF is due to ET(1)-derived vasoconstriction. S-0139 has potential for preventing EPO-induced and ET(1)-mediated RCBF reduction." }, { "pmid": "10513557", "year": 1999, "title": "Role of calcitonin gene-related peptide and capsaicin-sensitive afferents in central thyrotropin-releasing hormone-induced hepatic hyperemia.", "title_en": null, "title_de": "Rolle des Calcitonin Gene-Related Peptide und capsaicinsensitiver Afferenzen bei der zentral durch Thyrotropin-Releasing-Hormon induzierten hepatischen Hyperämie.", "journal": "European journal of pharmacology", "authors": "Tamori et al.", "author_search": "tamori tamori", "doi": "10.1016/s0014-2999(99)00527-0", "doi_url": "https://doi.org/10.1016/s0014-2999(99)00527-0", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/10513557/", "url": "https://h2medicine.org/studies/study-tamori-1999-calcitonin-gene-related-peptide/", "methods": [ "inhalation", "saline-iv" ], "indications": [ "liver", "neurology" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "1999 · Tamori — Role of calcitonin gene-related peptide and capsaicin-sensitive afferents in central thyrotropin-releasing hormone-induced hepatic hyperemia.", "summary": "This animal study in anesthetized rats demonstrates that central (intracisternal) injection of a TRH analogue increases hepatic blood flow via capsaicin-sensitive afferent neurons and CGRP — and that blocking either pathway completely abolishes this effect. Molecular hydrogen was used exclusively as a measurement tool (hydrogen gas clearance) to quantify liver blood flow, not as a therapeutic agent. (European Journal of Pharmacology, 1999.)", "assessment": "This is an animal neurophysiology/pharmacology study — it is not a therapeutic H₂ study. Molecular hydrogen was used solely as a measurement tool (clearance method) for hepatic blood flow, not as an intervention. The findings relate to a specific neuronal signalling pathway for liver perfusion regulation — not to any H₂ health effect. Results are not transferable to human clinical practice without further study. The hydrogen connection is purely methodological.", "abstract": "The involvement of capsaicin-sensitive afferent neurons and calcitonin gene-related peptide (CGRP) in the central thyrotropin-releasing hormone (TRH)-induced hepatic hyperemia was investigated in urethane anesthetized rats. Both systemic capsaicin pretreatment and intravenous administration of CGRP receptor antagonist, human CGRP-(8-37), completely abolished the stimulatory effect of hepatic blood flow induced by intracisternal injection of TRH analog (RX-77368; p-Glu-His-(3,3'-dimethyl)-Pro-NH2, 100 ng), assessed by the hydrogen gas clearance method. These data demonstrate the involvement of capsaicin-sensitive afferent neurons and CGRP in the central TRH-induced stimulation of hepatic blood flow.", "conclusion": "Both systemic capsaicin pretreatment and intravenous administration of CGRP receptor antagonist, human CGRP-(8-37), completely abolished the stimulatory effect of hepatic blood flow induced by intracisternal injection of TRH analog (RX-77368; p-Glu-His-(3,3'-dimethyl)-Pro-NH2, 100 ng), assessed by the hydrogen gas clearance method. These data demonstrate the involvement of capsaicin-sensitive affe" }, { "pmid": "10217412", "year": 1999, "title": "CTAB-mediated enrichment for active forms of novel dimeric maxizymes.", "title_en": null, "title_de": "CTAB-vermittelte Anreicherung aktiver Formen neuartiger dimerer Maxizyme.", "journal": "FEBS letters", "authors": "Nakayama et al.", "author_search": "nakayama nakayama", "doi": "10.1016/s0014-5793(99)00325-7", "doi_url": "https://doi.org/10.1016/s0014-5793(99)00325-7", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/10217412/", "url": "https://h2medicine.org/studies/study-nakayama-1999-ctab-mediated-enrichment-active/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "1999 · Nakayama — CTAB-mediated enrichment for active forms of novel dimeric maxizymes.", "summary": "This in-vitro study shows that the cationic detergent CTAB dramatically enhances the activity of dimeric ribozymes called maxizymes, by promoting the conversion of inactive conformations into active forms. In the most striking case, the activity of the least stable maxizyme was enhanced 100-fold. The „hydrogen“ connection is limited to hydrogen bonds stabilising inactive RNA conformations that CTAB disrupts. (FEBS Letters, 1999.)", "assessment": "This is a basic in-vitro RNA biochemistry study with no relevance to molecular H₂ therapy. The mention of „hydrogen“ refers to intramolecular hydrogen bonds in RNA secondary structure — a completely different chemical phenomenon from molecular H₂ gas. The study is of interest for gene therapy and RNA engineering. Readers looking for H₂ health evidence will find nothing relevant here. The inclusion in a hydrogen database appears to be a false-positive keyword match.", "abstract": "We demonstrated previously that shortened forms of (stem II-deleted) hammerhead ribozymes with low intrinsic activity form very active dimers with a common stem II (very active short ribozymes capable of forming dimers were designated maxizymes). As a result of such a dimeric structure, heterodimeric maxizymes are potentially capable of cleaving a substrate at two different sites simultaneously. In this case, active heterodimers are in equilibrium with inactive homodimers. Longer forms of common stem II can lead to enrichment of the active heterodimers in vitro. In this study, we investigated whether the cationic detergent CTAB, which is known to enhance strand displacement of nucleic acids, might inhibit the dimerization of maxizymes. Significantly, under all conditions examined, CTAB instead enhanced the activity of a variety of maxizymes, with the extent of enhancement depending on the conditions. The activity of our least stable, least active maxizyme was enhanced 100-fold by CTAB. The strand displacement activity of CTAB thus appears to enhance the conversion of alternative conformations of inactive maxizymes, with intra- and inter-molecular hydrogen bonds, to active forms. Thus, our smallest maxizyme can also be considered a potential candidate for a gene-inactivating agent in vivo, in view of the fact that various facilitators of strand displacement reactions are known to exist in vivo (indeed, a separate experiment in cell culture supported the conclusion that our smallest maxizyme is a good gene-inactivating agent). Although activities of ribozymes in vitro do not necessarily reflect their activities in vivo, our findings suggest that the activity of ribozymes in vivo can be better estimated by running ribozyme kinetics in the presence of CTAB in vitro.", "conclusion": "Thus, our smallest maxizyme can also be considered a potential candidate for a gene-inactivating agent in vivo, in view of the fact that various facilitators of strand displacement reactions are known to exist in vivo (indeed, a separate experiment in cell culture supported the conclusion that our smallest maxizyme is a good gene-inactivating agent). Although activities of ribozymes in vitro do no" }, { "pmid": "9914304", "year": 1999, "title": "Anaerobic transformation of quercetin-3-glucoside by bacteria from the human intestinal tract.", "title_en": null, "title_de": "Anaerobe Transformation von Quercetin-3-glucosid durch Bakterien aus dem menschlichen Darmtrakt.", "journal": "Archives of microbiology", "authors": "Schneider et al.", "author_search": "schneider schneider", "doi": "10.1007/s002030050682", "doi_url": "https://doi.org/10.1007/s002030050682", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/9914304/", "url": "https://h2medicine.org/studies/study-schneider-1999-anaerobic-transformation-quercetin-glucoside/", "methods": [ "unspecified" ], "indications": [ "sports-exercise" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "1999 · Schneider — Anaerobic transformation of quercetin-3-glucoside by bacteria from the human intestinal tract.", "summary": "This in-vitro study identifies two types of intestinal bacteria — Enterococcus casseliflavus and Eubacterium ramulus — capable of degrading the plant flavonoid quercetin-3-glucoside under anaerobic conditions. Molecular hydrogen is one of several minor fermentation byproducts detected. The study provides insight into how gut bacteria metabolise dietary polyphenols. (Archives of Microbiology, 1999.)", "assessment": "This is a basic in-vitro gut microbiology study — it is not relevant to H₂ therapy. Molecular hydrogen appears only as a trace fermentation byproduct and is not the subject of investigation. The findings are relevant to polyphenol metabolism and gut microbiome research. No therapeutic H₂ conclusions can be drawn from this paper. The inclusion in an H₂ database is likely a keyword-based false positive.", "abstract": "From human feces two phenotypically different types of bacteria were isolated on quercetin-3-glucoside as carbon and energy source. Isolates of one type were identified as strains of Enterococcus casseliflavus. They utilized the sugar moiety of the glycoside, but did not degrade the aglycon further. The sugar moiety (4 mM) was fermented to 5.5 +/- 2.1 mM formate, 2.1 +/- 0.7 mM acetate, 1.6 +/- 0.3 mM l-lactate, and 1.3 +/- 0.4 mM ethanol. The second type of isolate was identified as Eubacterium ramulus. This organism was capable of degrading the aromatic ring system. Growing cultures of Eubacterium ramulus converted 5 mM quercetin-3-glucoside to 1.7 +/- 0.6 mM 3,4-dihydroxyphenylacetic acid, 7.6 +/- 1.0 mM acetate, and 4.0 +/- 0.4 mM butyrate. Molecular hydrogen, 3,4-dihydroxybenzaldehyde, and ethanol were detected in small amounts. Phloroglucinol was a transient intermediate in the breakdown of quercetin-3-glucoside. Eubacterium ramulus did not grow on the aglycon quercetin or the ring-fission intermediate phloroglucinol, but cleaved the flavonoid ring system when glucose was present as a cosubstrate. The most probable number of quercetin-3-glucoside-degrading bacteria determined in nine human fecal samples was 10(7)-10(9)/g dry mass. Isolates from these experiments were all identified as Eubacterium ramulus.", "conclusion": "The most probable number of quercetin-3-glucoside-degrading bacteria determined in nine human fecal samples was 10(7)-10(9)/g dry mass. Isolates from these experiments were all identified as Eubacterium ramulus." }, { "pmid": "9515746", "year": 1998, "title": "13C breath test in gastroenterological practice.", "title_en": null, "title_de": "¹³C-Atemtest in der gastroenterologischen Praxis.", "journal": "Scandinavian journal of gastroenterology. Supplement", "authors": "Swart et al.", "author_search": "swart swart", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/9515746/", "url": "https://h2medicine.org/studies/study-swart-1998-13c-breath-test-gastroenterological/", "methods": [ "inhalation" ], "indications": [ "liver" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "1998 · Swart — ¹³C breath test in gastroenterological practice.", "summary": "This review summarises the use of breath tests — including both hydrogen gas excretion and ¹³C-labelled carbon dioxide — in gastroenterological practice as non-invasive alternatives to invasive diagnostic procedures. Applications include gastric emptying, H. pylori detection, small bowel bacterial overgrowth, pancreatic function, and liver metabolic capacity. (Scandinavian Journal of Gastroenterology. Supplement, 1998.)", "assessment": "This is a review of diagnostic breath-test methodology in gastroenterology. The hydrogen gas discussed is a diagnostic biomarker produced by gut bacteria during carbohydrate fermentation — it is not molecular H₂ as a therapeutic agent. The review provides a solid overview of clinical breath-test applications but has no relevance to H₂ supplementation, H₂ water, or H₂ inhalation therapy.", "abstract": "Breath tests (BTs) are used in gastroenterological practice to study (patho)physiological and metabolic processes in an indirect way. In these tests the appearance in breath of a metabolite of a specific test substance is studied. The assumption underlying each BT is that one step-the process of interest-in the absorption and metabolism of the tracer is rate-limiting. Both hydrogen gas excretion and carbon dioxide appearance in breath can be studied. When a carbon-labelled test substance is used. the stable isotope 13C is preferred to the radioactive isotope 14C. Measurements of 13C in expired air are performed by mass spectrometry. Because of the indirect nature of BTs, involving a sequence of reactions and metabolic pools, they usually supply semiquantitative data. The tests are nevertheless useful because they often replace invasive techniques with a simple procedure that is safe because there is no radioactivity involved. BTs have been used to measure gastric emptying, the presence of Helicobacter pylori in the stomach, small-bowel bacterial overgrowth, exocrine pancreatic function as well as liver metabolic capacity; other potential applications of BTs are being studied.", "conclusion": "The tests are nevertheless useful because they often replace invasive techniques with a simple procedure that is safe because there is no radioactivity involved. BTs have been used to measure gastric emptying, the presence of Helicobacter pylori in the stomach, small-bowel bacterial overgrowth, exocrine pancreatic function as well as liver metabolic capacity; other potential applications of BTs ar" }, { "pmid": "9867093", "year": 1998, "title": "Fructose-sorbitol malabsorption and symptom provocation in irritable bowel syndrome: relationship to enteric hypersensitivity and dysmotility.", "title_en": null, "title_de": "Fructose-Sorbit-Malabsorption und Symptomprovokation beim Reizdarmsyndrom: Beziehung zu enteraler Hypersensitivität und Dysmotilität.", "journal": "Scandinavian journal of gastroenterology", "authors": "Evans et al.", "author_search": "evans evans", "doi": "10.1080/00365529850172502", "doi_url": "https://doi.org/10.1080/00365529850172502", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/9867093/", "url": "https://h2medicine.org/studies/study-evans-1998-fructose-sorbitol-malabsorption-symptom/", "methods": [], "indications": [ "other" ], "evidence_level": 3, "human": true, "therapeutic": false, "h2category": "breath-test", "headline": "1998 · Evans — Fructose-sorbitol malabsorption and symptom provocation in irritable bowel syndrome: relationship to enteric hypersensitivity and dysmotility.", "summary": "In 15 female IBS patients, fructose-sorbitol mixtures provoked symptoms and elevated breath hydrogen in those who malabsorbed the sugars — but symptom severity was not associated with the presence of jejunal hypersensitivity or dysmotility. Breath H₂ is a fermentation biomarker here, not a therapeutic agent. (Scandinavian Journal of Gastroenterology, 1998.)", "assessment": "This is an honest null-finding study with implications for IBS management and FODMAP research. Breath H₂ was used as a validated diagnostic marker of colonic fermentation. H₂ is not a therapeutic agent here — it is an endogenous byproduct of sugar fermentation measured to confirm malabsorption. Limitations: small sample (n = 15, all female); no randomization; single-center. The negative finding regarding hypersensitivity and dysmotility as predictors of symptom response is the scientifically interesting contribution. This study should not be included in an H₂ therapy database without a clear disclaimer.", "abstract": "BACKGROUND: Fructose-sorbitol (F-S) mixtures can provoke symptoms in irritable bowel syndrome (IBS) patients, and a proportion of IBS patients also have enteric hypersensitivity to distension. We hypothesized, therefore, that sugar malabsorption and fermentation to produce hydrogen gas may provoke symptoms to a greater extent in IBS patients hypersensitive to distension than in those patients without such hypersensitivity. Our aims were therefore to compare, in IBS patients, symptoms and breath hydrogen responses after F-S, on the basis of jejunal sensitivity and jejunal motor function. METHODS: Fifteen female IBS patients (44 +/- 15 years) underwent, on separate occasions, 3-h breath hydrogen analyses after ingesting 10 g lactulose and 25 g fructose with 5 g sorbitol. Jejunal sensitivity and motor function were determined by balloon distension and 24-h manometry studies, respectively. Cumulative symptom scores and breath hydrogen production were analysed on the basis of the presence or absence of jejunal hypersensitivity and dysmotility. RESULTS: Four and seven patients had jejunal hypersensitivity for initial perception and pain, respectively. Eleven, nine, and nine patients had jejunal dysmotility for fasting phase 3, phase 2, and fed motor activity, respectively. Of the patients with symptom provocation after F-S (n = 8 within 3 h, n = 12 within 12 h) or with F-S malabsorption (n = 10), the relative proportion did not differ on the basis of the presence or absence of jejunal hypersensitivity or of motor dysfunction. Symptom scores and hydrogen production also were not different in these subgroups. CONCLUSIONS: Although carbohydrate malabsorption can provoke symptoms in some IBS patients, there is no consistent association between such a phenomenon and the presence of either jejunal hypersensitivity or dysmotility.", "conclusion": "Although carbohydrate malabsorption can provoke symptoms in some IBS patients, there is no consistent association between such a phenomenon and the presence of either jejunal hypersensitivity or dysmotility." }, { "pmid": "9771858", "year": 1998, "title": "Energy expenditure and net substrate utilization in men ingesting usual and high amounts of nonstarch polysaccharide.", "title_en": null, "title_de": "Energieumsatz und Netto-Substratverwertung bei Männern, die übliche und hohe Mengen an Nicht-Stärke-Polysacchariden zu sich nehmen", "journal": "The American journal of clinical nutrition", "authors": "Poppitt et al.", "author_search": "poppitt poppitt", "doi": "10.1093/ajcn/68.4.820", "doi_url": "https://doi.org/10.1093/ajcn/68.4.820", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/9771858/", "url": "https://h2medicine.org/studies/study-poppitt-1998-energy-expenditure-net-substrate/", "methods": [], "indications": [ "metabolic", "sports-exercise" ], "evidence_level": 3, "human": true, "therapeutic": false, "h2category": "breath-test", "headline": "1998 · Poppitt et al. — Energy expenditure and net substrate utilization in men ingesting usual and high amounts of nonstarch polysaccharides", "summary": "A high-fibre (nonstarch polysaccharide) diet produced no measurable thermogenic effect and no short-term change in body composition in healthy men. Breath hydrogen and methane were measured as metabolic by-products of gut fermentation — not as therapeutic agents. The practical finding: simply eating more fibre does not boost calorie burning. (American Journal of Clinical Nutrition, 1998.)", "assessment": "Important context: this study does not investigate molecular hydrogen (H₂) as a therapeutic intervention. Breath hydrogen is used exclusively as a fermentation marker to assess carbohydrate malabsorption and gut bacterial activity — a standard gastroenterological tool. The primary topic is dietary fibre and energy metabolism. The study is well-designed (randomised crossover, metabolic ward, 24 h calorimetry, n = 12), and its null finding is clearly stated. Limitations: small sample, short duration (~3 weeks), controlled metabolic ward conditions may not reflect free-living behaviour. Not relevant to H₂ therapy.", "abstract": "BACKGROUND: Diets intrinsically high in nonstarch polysaccharides (NSPs) are frequently advised for body weight regulation and health, but the consequences for energy expenditure and fuel selection are undetermined. OBJECTIVE: We determined whether energy expenditure and fuel selection differ when men consume a diet intrinsically higher in NSP than a usual mixed diet. DESIGN: A randomized crossover design was used in which 12 healthy men were fed a maintenance diet for approximately 3 wk in a metabolic suite. By judicial choice of food exchanges, the usual- and high-NSP diets were similar in protein, fat, and carbohydrate contents. Twenty-four-hour, indirect, open-circuit calorimetry was performed, including measurements of total hydrogen gas and methane. Participants were weight stable (within 2 kg for 3 wk), entered an 11-m3 calorimetry chamber for 36 h with measurements taken in the last 24 h, and underwent a strictly controlled program of moderate physical activity (1.3 x basal metabolic rate). RESULTS: The mean total 24-h energy expenditure and percentages from protein, fat, and carbohydrate metabolism were 10 MJ/d and 16%, 35%, and 48%, respectively. Differences (mean+/-SEM) between the 2 diets were only -0.005+/-0.130 MJ/d, -0.3+/-1.3%, -0.2+/-2.0%, and 0.6+/-2.2%, respectively, and were nonsignificant (P> 0.2). CONCLUSIONS: There was no thermogenic response to the high-NSP diet, which would be advantageous for body weight control, and no short-term influence on body composition, as may be judged from a lack of change in protein, fat, or carbohydrate metabolism.", "conclusion": "There was no thermogenic response to the high-NSP diet, which would be advantageous for body weight control, and no short-term influence on body composition, as may be judged from a lack of change in protein, fat, or carbohydrate metabolism." }, { "pmid": "9492232", "year": 1998, "title": "A one-hour active coping stressor reduces small bowel transit time in healthy young adults.", "title_en": null, "title_de": "Ein einstündiger aktiver Bewältigungsstressor verkürzt die Dünndarmpassagezeit bei gesunden jungen Erwachsenen", "journal": "Psychosomatic medicine", "authors": "Ditto et al.", "author_search": "ditto ditto", "doi": "10.1097/00006842-199801000-00002", "doi_url": "https://doi.org/10.1097/00006842-199801000-00002", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/9492232/", "url": "https://h2medicine.org/studies/study-ditto-1998-one-hour-active-coping/", "methods": [], "indications": [ "sports-exercise" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "breath-test", "headline": "1998 · Ditto et al. — A one-hour active coping stressor reduces small bowel transit time in healthy young adults", "summary": "A one-hour stress task (avoiding mild electric shocks by playing video games) reduced small intestine transit time from 79 to 55 minutes in healthy males. The reduction was linked to cardiac sympathetic activity, suggesting the gut–brain axis responds rapidly to psychological stress. Hydrogen is used here as a diagnostic breath-test marker only — not as a therapeutic agent. (Psychosomatic Medicine, 1998.)", "assessment": "Important context: this study does not investigate molecular hydrogen (H₂) as a therapeutic intervention. Breath hydrogen is used as a diagnostic tracer via the lactulose breath test — a standard gastroenterological method to measure small bowel transit time. The study topic is psychosomatic medicine and gut motility. The design is a well-controlled crossover (n = 12, within-subject comparison). Limitations: small all-male student sample, laboratory stressor may not generalise, single-session design. Not relevant to H₂ therapy.", "abstract": "OBJECTIVE: To examine the effect of a prolonged active coping stressor on the transit of a substance from the mouth through small intestine in normal human volunteers. METHOD: Twelve healthy undergraduate males were administered 10 g of the nonabsorbable carbohydrate lactulose in two experimental sessions. In normal individuals, lactulose produces hydrogen gas upon exposure to bacteria residing in the colon. Repeated measurements of breath hydrogen were obtained for 2 hours. In one session, subjects rested quietly for the 2-hour period. In the other counterbalanced session, subjects avoided mild electric shocks by playing videogames for the first hour. RESULTS: Stress produced a statistically and clinically significant reduction in mean transit time, from 79 to 55 minutes. The magnitude of stress-induced reduction in small bowel transit time was significantly correlated with change in an index of cardiac sympathetic activity, pulse transit time. CONCLUSIONS: A prolonged active coping stressor with minimal motor requirements produced a decrease in small bowel transit time comparable with that observed in several studies of the effects of physical exercise and in comparisons between normal controls and patients with diarrhea-predominant irritable bowel syndrome.", "conclusion": "A prolonged active coping stressor with minimal motor requirements produced a decrease in small bowel transit time comparable with that observed in several studies of the effects of physical exercise and in comparisons between normal controls and patients with diarrhea-predominant irritable bowel syndrome." }, { "pmid": "8870180", "year": 1996, "title": "Magnetization transfer magnetic resonance imaging: a clinical review.", "title_en": null, "title_de": "Magnetisierungstransfer-Magnetresonanztomographie: eine klinische Übersichtsarbeit", "journal": "Topics in magnetic resonance imaging : TMRI", "authors": "Mehta et al.", "author_search": "mehta mehta", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/8870180/", "url": "https://h2medicine.org/studies/study-mehta-1996-magnetization-transfer-magnetic-resonance/", "methods": [ "unspecified" ], "indications": [ "metabolic", "sports-exercise", "neurology", "cancer", "skin-aging" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "1996 · Mehta — Magnetization Transfer Magnetic Resonance Imaging: A Clinical Review", "summary": "Magnetization transfer (MT) is a magnetic resonance imaging technique that exploits the interaction between free water protons and protons bound to macromolecules — providing tissue contrast that reveals structural integrity beyond conventional T1, T2, and proton-density images. This clinical review covers the physics of MT, normal brain appearances, and key neuroradiological applications including multiple sclerosis, white-matter lesions, tumors, and vascular imaging. (Topics in Magnetic Resonance Imaging, 1996.)", "assessment": "This paper is a diagnostic imaging review, not a hydrogen therapy study. It describes magnetization transfer MRI physics and neuroradiological applications in the 1990s — a legitimate and well-established technique. Its connection to „hydrogen” is purely through MRI proton physics (¹H NMR), not through molecular H₂ or hydrogen-rich water. No therapeutic claims about H₂ should be drawn from this work. For researchers looking for clinical evidence on H₂ as a therapeutic agent, this paper is not relevant.", "abstract": "Magnetic resonance imaging has traditionally used the T1 and T2 relaxation times and proton density (PD) of tissue water (hydrogen protons) to manipulate contrast. Magnetization transfer (MT) is a new form of tissue contrast based on the physical concept that tissues contain two or more separate populations of hydrogen protons: a highly mobile (free) hydrogen (water) pool, Hr, and an immobile (restricted) hydrogen pool, Hr, the latter being those protons bound to large macromolecular proteins and lipids, such as those found in such cellular membranes as myelin. Direct observation of the Hr magnetization pool is normally not possible because of its extremely short T2 time (< 200 microseconds). But saturation of the restricted pool will have a detectable effect on the mobile (free) proton pool. Saturation of the restricted pool decreases the signal of the free pool by transferring the restricted pool's saturation. Exchange of magnetization between the free and restricted hydrogen protons is a substantial mechanism for spin-lattice (T1) relaxation in tissues and the physical basis of MT. Through an appropriately designed pulse sequence, magnetization transfer contrast (MTC) can be produced. MT contrast is different from T1, T2, and PD, and it likely reflects the structural integrity of the tissue being imaged. A variety of clinically important uses of MT have emerged. In this clinical review of the neuroradiological applications of MT, we briefly review the physics of MT, the appearance of normal brain with MT, and the use of MT as a method of contrast enhancement/background suppression and in tissue characterization, such as evaluation of multiple sclerosis and other white-matter lesions and tumors. The role of MT in small-vessel visualization on three-dimensional time-of-flight magnetic resonance angiography and in head and neck disease and newer applications of MT are also elaborated.", "conclusion": "In this clinical review of the neuroradiological applications of MT, we briefly review the physics of MT, the appearance of normal brain with MT, and the use of MT as a method of contrast enhancement/background suppression and in tissue characterization, such as evaluation of multiple sclerosis and other white-matter lesions and tumors. The role of MT in small-vessel visualization on three-dimensi" }, { "pmid": "8613657", "year": 1996, "title": "How much lactose is low lactose?", "title_en": null, "title_de": "Wie viel Lactose ist wenig Lactose?", "journal": "Journal of the American Dietetic Association", "authors": "Hertzler et al.", "author_search": "hertzler hertzler", "doi": "10.1016/s0002-8223(96)00074-0", "doi_url": "https://doi.org/10.1016/s0002-8223(96)00074-0", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/8613657/", "url": "https://h2medicine.org/studies/study-hertzler-1996-how-much-lactose-low/", "methods": [], "indications": [ "other" ], "evidence_level": 3, "human": true, "therapeutic": false, "h2category": "breath-test", "headline": "1996 · Hertzler et al. — How much lactose is low lactose?", "summary": "Lactose-intolerant adults tolerated up to 6 g of lactose per serving without significant symptoms, even though fermentation could be detected at that dose by breath hydrogen testing. Only doses of 12 g or more triggered abdominal pain; flatulence did not increase until 20 g. Breath hydrogen serves here as a diagnostic fermentation marker, not as a therapeutic agent. (Journal of the American Dietetic Association, 1996.)", "assessment": "Important context: this study does not investigate molecular hydrogen (H₂) as a therapeutic intervention. Breath hydrogen is used exclusively as a diagnostic marker of colonic fermentation of undigested lactose. The study is a well-designed double-blind randomised dose-escalation trial (n = 13 lactose maldigesters, 5 challenge doses). Its findings are useful for dietary management of lactose intolerance. Limitations: small sample, single-dose challenges (not with real foods or meals), free-living adults may metabolise lactose differently in the context of a full meal. Not relevant to H₂ therapy.", "abstract": "OBJECTIVE: To test the hypothesis that complete elimination of lactose is not necessary to ensure tolerance by lactose maldigesters. DESIGN: Double-blind, randomized protocol in which challenge doses of 0, 2, 6, 12, and 20 g lactose in water were fed to subjects after a 12-hour fast. SUBJECTS: 13 healthy, free-living adults who were lactose maldigesters. MAIN OUTCOME MEASURES: Breath hydrogen production (a measure of maldigestion) and symptom response to each challenge dose. STATISTICAL ANALYSIS: Analysis of variance was done to determine overall differences in mean hydrogen gas production (peak and sum of hours 1 through 8). Friedman's test was used to determine overall differences in the mean ranks for each symptom. Fisher's least significant difference test was used for multiple comparisons for hydrogen and symptom and data. RESULTS: Hydrogen production after consumption of the 0- and 2-g lactose doses was not significantly different. Hydrogen production increased with the 6-g dose. Intensity of abdominal pain increased when the dose of lactose was 12 g. Episodes of flatulence did not increase until the dose reached 20 g. No significant differences in the occurrence of diarrhea were observed after the five treatments. CONCLUSIONS: No significant increase in breath hydrogen production or intolerance symptoms occurred after consumption of a 2-g dose of lactose. Up to 6 g was tolerated, even though maldigestion could be measured at the 6-g dose. Thus, lactose maldigesters may be able to tolerate foods containing 6 g lactose or less per serving, such as hard cheeses and small servings (120 mL or less) of milk.", "conclusion": "No significant increase in breath hydrogen production or intolerance symptoms occurred after consumption of a 2-g dose of lactose. Up to 6 g was tolerated, even though maldigestion could be measured at the 6-g dose. Thus, lactose maldigesters may be able to tolerate foods containing 6 g lactose or less per serving, such as hard cheeses and small servings (120 mL or less) of milk." }, { "pmid": "9127504", "year": 1996, "title": "Radiotoxicity of tritiated water and tritiated hydrogen.", "title_en": null, "title_de": "Radiotoxizität von tritiiertem Wasser und tritiiertem Wasserstoff", "journal": "Arhiv za higijenu rada i toksikologiju", "authors": "Franić", "author_search": "franić franić", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/9127504/", "url": "https://h2medicine.org/studies/study-franic-1996-radiotoxicity-tritiated-tritiated/", "methods": [ "inhalation" ], "indications": [ "cancer", "respiratory" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "1996 · Franić — Radiotoxicity of Tritiated Water and Tritiated Hydrogen", "summary": "Tritiated water (HTO) is far more radiotoxic than tritiated hydrogen gas (HT): inhaling tritiated H₂ gas leads to partial oxidation into HTO in the lungs, meaning the effective dose is higher than previously assumed — and the official toxicity ratio of 1:25,000 (HT vs. HTO) should be corrected to 1:12,000. This theoretical dosimetry analysis has implications for radiation protection standards, not for therapeutic use of hydrogen. (Arhiv za higijenu rada i toksikologiju, 1996.)", "assessment": "This is a theoretical dosimetry analysis in the field of radiation protection, not a hydrogen therapy study. It concerns radioactive tritium (³H), a completely different substance from stable molecular hydrogen (H₂). No conclusions about therapeutic H₂ can be drawn from this work. Its value lies in correcting an occupational safety standard — a narrow but technically important contribution for radiation protection experts. Researchers interested in molecular H₂ as an antioxidant or therapeutic agent will find nothing applicable here.", "abstract": "Tritium in the form of tritiated water is much more radiotoxic than tritiated hydrogen. The effective dose which results from tritiated water as the oxidation product of Inhaled tritiated hydrogen gas makes about 55 per cent of the effective dose due to direct irradiation of the lungs by tritiated hydrogen only. The inclusion of the dose due to the production of tritiated water would tower the relative toxicity ratio as well as the value of derived air concentration for tritiated hydrogen. Therefore, to assess the health hazard from tritium exposure, for the two species the relative significance of 1:12,000 should be used, instead of the relative radiotoxicity ratio of 1:25,000 as given by the International Commission on Radiological Protection.", "conclusion": "The inclusion of the dose due to the production of tritiated water would tower the relative toxicity ratio as well as the value of derived air concentration for tritiated hydrogen. Therefore, to assess the health hazard from tritium exposure, for the two species the relative significance of 1:12,000 should be used, instead of the relative radiotoxicity ratio of 1:25,000 as given by the Internation" }, { "pmid": "7796506", "year": 1995, "title": "Assessment of left-to-right intracardiac shunting by velocity-encoded, phase-difference magnetic resonance imaging. A comparison with oximetric and indicator dilution techniques.", "title_en": null, "title_de": "Beurteilung des intrakardialen Links-Rechts-Shunts mittels geschwindigkeitskodierter Phasenkontrast-Magnetresonanztomographie", "journal": "Circulation", "authors": "Hundley et al.", "author_search": "hundley hundley", "doi": "10.1161/01.cir.91.12.2955", "doi_url": "https://doi.org/10.1161/01.cir.91.12.2955", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/7796506/", "url": "https://h2medicine.org/studies/study-hundley-1995-left-right-intracardiac-shunting/", "methods": [], "indications": [ "cardiovascular", "respiratory", "skin-aging" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "tracer-clearance", "headline": "1995 · Hundley et al. — Assessment of left-to-right intracardiac shunting by velocity-encoded, phase-difference magnetic resonance imaging", "summary": "MRI flow measurements in the major heart vessels agreed very well (r = 0.94) with invasive catheterisation data in detecting and quantifying left-to-right intracardiac shunts in 21 adults. Hydrogen inhalation was used as the clinical reference method to confirm the presence of shunting — not as a therapeutic agent. The practical finding: non-invasive MRI can replace catheterisation for shunt assessment. (Circulation, 1995.)", "assessment": "Important context: this study does not investigate molecular hydrogen (H₂) as a therapeutic intervention. Hydrogen inhalation is used as the established clinical reference test for detecting intracardiac left-to-right shunts — a diagnostic procedure used in cardiac catheterisation laboratories. The study topic is diagnostic cardiology and cardiac MRI validation. The design is prospective and blinded (n = 21). Limitations: single-centre, small sample, only large-vessel MRI measurements reported. Not relevant to H₂ therapy.", "abstract": "BACKGROUND: Velocity-encoded, phase-difference magnetic resonance imaging (MRI) has been shown to provide an accurate assessment of shunt magnitude in patients with large atrial septal defects, but its ability to determine shunt magnitude in patients with intracardiac left-to-right shunts of various locations and sizes has not been evaluated in a prospective and blinded manner. The objective of the present study was to determine whether velocity-encoded, phase-difference MRI can assess the magnitude of intracardiac left-to-right shunting in humans. METHODS AND RESULTS: Twenty-one subjects (15 women and 6 men; age range, 15 to 72 years) underwent velocity-encoded, phase-difference MRI measurements of flow in the proximal aorta and pulmonary artery, followed immediately by cardiac catheterization. The presence of left-to-right intracardiac shunting was assessed with hydrogen inhalation, after which shunt magnitude was measured by the oximetric and indocyanine green techniques. Of the 21 patients, 12 had left-to-right intracardiac shunting detected by hydrogen inhalation. There was a good correlation (r = .94) between the invasive and MRI assessments of shunt magnitude. In comparison to oximetry and indocyanine green, MRI correctly identified the 12 patients with a ratio of pulmonary to systemic flow (Qp/Qs) of < 1.5 (9 without intracardiac shunting and 3 with small shunts) and the 9 patients with a Qp/Qs of > or = 1.5 (6 with atrial septal defect, 1 with ventricular septal defect, 1 with patent ductus arteriosus, and 1 with both atrial septal defect and patent ductus arteriosus). CONCLUSIONS: Compared with measurements obtained during cardiac catheterization, velocity-encoded, phase-difference MRI measurements of flow in the proximal great vessels can reliably assess the magnitude of intracardiac left-to-right shunting.", "conclusion": "Compared with measurements obtained during cardiac catheterization, velocity-encoded, phase-difference MRI measurements of flow in the proximal great vessels can reliably assess the magnitude of intracardiac left-to-right shunting." }, { "pmid": "7548544", "year": 1995, "title": "Energetics of molecular hydrogen oxidation in the oral pathogen Campylobacter rectus.", "title_en": null, "title_de": "Energetik der Oxidation von molekularem Wasserstoff im oralen Pathogen Campylobacter rectus", "journal": "Clinical infectious diseases : an official publication of the Infectious Diseases Society of America", "authors": "Gillespie et al.", "author_search": "gillespie gillespie", "doi": "10.1093/clinids/20.supplement_2.s172", "doi_url": "https://doi.org/10.1093/clinids/20.supplement_2.s172", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/7548544/", "url": "https://h2medicine.org/studies/study-gillespie-1995-energetics-oxidation-oral-pathogen/", "methods": [ "drinking-hrw" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "1995 · Gillespie — Energetics of Molecular Hydrogen Oxidation in the Oral Pathogen Campylobacter rectus", "summary": "This in-vitro study examined how the oral pathogen Campylobacter rectus oxidizes molecular hydrogen (H₂) as an energy source — a fundamental microbiology question about bacterial hydrogen metabolism in the oral cavity. No abstract is publicly available; details are accessible via the DOI. (Clinical Infectious Diseases, 1995.)", "assessment": "This is an in-vitro microbiology study on bacterial H₂ metabolism — not a therapeutic hydrogen study. Because no abstract is available in the record, a full evaluation is not possible here. This is not evidence for any human health effect of H₂. The study is of basic scientific interest for understanding bacterial energy metabolism in the oral microbiome. Readers seeking clinical evidence on H₂ therapy should consult the original paper directly via its DOI.", "abstract": null, "conclusion": null }, { "pmid": "7919894", "year": 1994, "title": "[Breath tests--a clarification of the topic].", "title_en": null, "title_de": "Atemtests: eine Klärung des Themas", "journal": "Bildgebung = Imaging", "authors": "Beglinger", "author_search": "beglinger beglinger", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/7919894/", "url": "https://h2medicine.org/studies/study-beglinger-1994-breath-tests-clarification-topic/", "methods": [ "inhalation" ], "indications": [ "other" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "1994 · Beglinger — Breath Tests: A Clarification of the Topic", "summary": "Breath tests measuring either hydrogen gas (H₂) or labeled carbon dioxide (¹³CO₂) in exhaled air represent a non-invasive diagnostic class for gastroenterological evaluation — this review clarifies their main indications and limitations. Hydrogen breath tests detect carbohydrate malabsorption and bacterial overgrowth by measuring H₂ produced by colonic bacteria. (Bildgebung = Imaging, 1994.)", "assessment": "This is a diagnostic review on gastroenterological breath testing — not a therapeutic hydrogen study. Hydrogen appears here as a diagnostic marker produced by colonic bacteria, not as a therapeutic agent. No therapeutic conclusions about molecular H₂ can be drawn from this paper. It is of practical clinical value for understanding non-invasive GI diagnostics, particularly carbohydrate malabsorption and small bowel bacterial overgrowth. Researchers looking for evidence on H₂ therapy will find this paper tangentially related at best.", "abstract": "Breath tests represent a new class of diagnostic tests to be used in gastroenterologic diagnostics. The breath tests depend basically on the quantification of either hydrogen gas or labeled carbon dioxide in the expired air. The main indications are presented and the limitations of the tests are discussed.", "conclusion": "The breath tests depend basically on the quantification of either hydrogen gas or labeled carbon dioxide in the expired air. The main indications are presented and the limitations of the tests are discussed." }, { "pmid": "7723185", "year": 1994, "title": "[Experimental and clinical studies on ischemic lesions of the large intestine].", "title_en": null, "title_de": "Experimentelle und klinische Studien zu ischämischen Läsionen des Dickdarms", "journal": "Nihon Ronen Igakkai zasshi. Japanese journal of geriatrics", "authors": "Mizushima et al.", "author_search": "mizushima mizushima", "doi": "10.3143/geriatrics.31.835", "doi_url": "https://doi.org/10.3143/geriatrics.31.835", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/7723185/", "url": "https://h2medicine.org/studies/study-mizushima-1994-experimental-ischemic-lesions-large/", "methods": [], "indications": [ "cardiovascular" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "tracer-clearance", "headline": "1994 · Mizushima et al. — Experimental and clinical studies on ischemic lesions of the large intestine", "summary": "Thrombi in peripheral small arteries appear to play a key role in causing ischemic lesions of the colon, based on both animal experiments and clinical observations in post-surgical human cases. Hydrogen gas clearance is used here as a blood flow measurement method — a standard research technique — not as a therapeutic agent. (Japanese Journal of Geriatrics, 1994.)", "assessment": "Important context: this study does not investigate molecular hydrogen (H₂) as a therapeutic intervention. The hydrogen gas clearance technique is a vascular physiology research method used to measure mucosal blood flow — completely unrelated to H₂ therapy. Additionally, this study is substantially animal-based (dog experiments) with only clinical observational data from human patients added for comparison. Limitations: animal model (dog) dominates the experimental data; human component is observational only; small cohort. Not relevant to H₂ therapy.", "abstract": "To clarify the pathogenesis and endoscopic features of ischemic lesions of the colon, experimental ischemia was induced in dogs by arterial ligation, gelfoam injection, and clipping. In addition, clinical and endoscopic features of ischemic lesions in ischemic colitis cases in human were studied. In the experimental model, arterial ligation including marginal arteries frequently induced erosions in the large intestine, whereas ligation of the colic artery alone did not induce apparent mucosal lesions of the large intestine. Gelfoam injection to produce thrombi into caudal mesenteric artery or middle colic artery induced ulcers with a high rate of incidence and frequently accompanied by intestinal perforation. Temporal impairment of blood supply by arterial clipping produced erosion, but not ulcers. A high incidence of erosion was obtained in a group that underwent clipping for a prolonged period and a group of receiving Alosenn. Mucosal blood flow measured by the hydrogen gas clearance method was significantly decreased at 1 hr and 4 hr after gelfoam injection compared with those after arterial ligation. In human cases of ischemia following arterial surgery, endoscopic features were similar to those lesions of the experimental ischemia induced by gelfoam injection. These results suggest that thrombi in peripheral small arteries may play a major role in the pathogenesis of ischemic lesions of the large intestine.", "conclusion": "In human cases of ischemia following arterial surgery, endoscopic features were similar to those lesions of the experimental ischemia induced by gelfoam injection. These results suggest that thrombi in peripheral small arteries may play a major role in the pathogenesis of ischemic lesions of the large intestine." }, { "pmid": "7932756", "year": 1994, "title": "Drug-protein interactions. Refined structures of three sulfonamide drug complexes of human carbonic anhydrase I enzyme.", "title_en": null, "title_de": "Arzneistoff–Protein-Interaktionen: Verfeinerte Strukturen dreier Sulfonamid-Arzneistoffkomplexe des humanen Carboanhydrase-I-Enzyms", "journal": "Journal of molecular biology", "authors": "Chakravarty et al.", "author_search": "chakravarty chakravarty", "doi": "10.1006/jmbi.1994.1655", "doi_url": "https://doi.org/10.1006/jmbi.1994.1655", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/7932756/", "url": "https://h2medicine.org/studies/study-chakravarty-1994-drug-protein-interactions-refined/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "1994 · Chakravarty — Drug–Protein Interactions: Refined Structures of Three Sulfonamide Drug Complexes of Human Carbonic Anhydrase I Enzyme", "summary": "This in-vitro crystallography study resolved the atomic structures of three sulfonamide drugs bound to human carbonic anhydrase I (HCAI) at 2 Å resolution, revealing how hydrogen bonds within the enzyme's active site determine inhibitor orientation and potency. The connection to hydrogen chemistry lies in the central role of hydrogen bonding networks — not in molecular H₂ therapy. (Journal of Molecular Biology, 1994.)", "assessment": "This is a structural biochemistry study in drug design — not a hydrogen therapy study. Hydrogen in this paper refers entirely to hydrogen bonds in protein–drug interactions, not to molecular H₂ or hydrogen-rich water. No implications for therapeutic H₂ use exist in this work. It is valuable for medicinal chemists and crystallographers studying carbonic anhydrase inhibitors, but has no connection to the molecular hydrogen medicine field.", "abstract": "N-unsubstituted sulfonamide drugs are widely used for opthalmic disorders. Inhibition of carbonic anhydrase enzyme is believed to be the chief reason for their therapeutic effects. Structures of three such sulfonamide drugs complexed to human carbonic anhydrase I enzyme (HCAI) refined crystallographically at 2 A resolution are reported here. The drug molecules are all bound in the active site of the enzyme, but among themselves show differences in the orientations of the sulfamido groups interacting with the essential zinc ion in the active site. The activity linked solvent molecule coordinated to zinc in the native enzyme is displaced by all the three sulfonamides. The active site loop of Leu198, Thr199 and His200 has been identified to be important for binding of the drug molecules due to their appreciable atomic displacements and intra-molecular hydrogen bonds arising out of their interactions with the sulfonamides. These interactions along with active site charge requirements are proposed to be responsible for the orientational differences of the sulfamido groups and also for differences in the inhibitory powers of the drugs. A hydrogen bond network involving solvent molecules and active site residues His200 and His67 amongst others in the native enzyme, is disrupted upon binding of methazolamide but not in the other two sulfonamides. This is the first crystallographic evidence of the possible involvement of His200 in the inhibition of HCAI. An important role of Thr199 in distinguishing between the substrate and inhibitor binding modes of HCO3- to the enzyme at high pH is also inferred.", "conclusion": "This is the first crystallographic evidence of the possible involvement of His200 in the inhibition of HCAI. An important role of Thr199 in distinguishing between the substrate and inhibitor binding modes of HCO3- to the enzyme at high pH is also inferred." }, { "pmid": "8062196", "year": 1994, "title": "Chemotherapy-induced lactose intolerance in adults.", "title_en": null, "title_de": "Chemotherapieinduzierte Lactoseintoleranz bei Erwachsenen", "journal": "Cancer", "authors": "Parnes et al.", "author_search": "parnes parnes", "doi": "10.1002/1097-0142(19940901)74:5<1629::aid-cncr2820740523>3.0.co;2-l", "doi_url": "https://doi.org/10.1002/1097-0142(19940901)74:5<1629::aid-cncr2820740523>3.0.co;2-l", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/8062196/", "url": "https://h2medicine.org/studies/study-parnes-1994-chemotherapy-induced-lactose-intolerance/", "methods": [], "indications": [ "cancer", "respiratory" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "breath-test", "headline": "1994 · Parnes et al. — Chemotherapy-induced lactose intolerance in adults", "summary": "Chemotherapy caused measurable lactose malabsorption in 30% of cancer patients, but symptomatic lactose intolerance developed in only 11%. The lactose breath hydrogen test was used as the diagnostic tool, not as a therapeutic intervention. Conclusion: routine restriction of dairy in chemotherapy patients is not warranted unless symptoms actually occur. (Cancer, 1994.)", "assessment": "Important context: this study does not investigate molecular hydrogen (H₂) as a therapeutic intervention. The lactose breath hydrogen test (LBHT) is a standard gastroenterological diagnostic method that measures exhaled hydrogen produced by colonic bacteria fermenting undigested lactose. The study topic is clinical oncology nutrition. Design: prospective with pre/post comparison (n = 27 chemotherapy patients). Limitations: heterogeneous cancer diagnoses and chemotherapy regimens; small sample; no long-term follow-up; no control group. Not relevant to H₂ therapy.", "abstract": "BACKGROUND: Anorexia and weight loss contribute to the morbidity and mortality from cancer. This study was designed to test the hypothesis that chemotherapy produces lactose intolerance which could have an adverse effect on the nutritional status of patients receiving cytotoxic drugs. METHODS: Twenty-seven patients were evaluated for the development of lactose intolerance during chemotherapy. Lactose breath hydrogen testing (LBHT) was used to assess lactose malabsorption objectively. This test is based on the principle that in patients with lactase deficiency, lactose is not hydrolyzed in the small intestine and ultimately is degraded by colonic bacteria. This results in the production of hydrogen gas, which is excreted by the lungs and can be quantified with a breath hydrogen analyzer. RESULTS: Of the 27 patients studied, 8 (30%) had an abnormal postchemotherapy LBHT results, and for the population as a whole, postchemotherapy LBHT values were significantly greater than prechemotherapy values (P = 0.04). However, only three patients (11%) showed clinical symptoms of lactose intolerance during the post-chemotherapy LBHT. Five patients had asymptomatic elevations in breath hydrogen excretion on prechemotherapy testing. One of these patients had a further increase in hydrogen excretion on Day 8 after chemotherapy, which was accompanied by symptoms of lactose intolerance. Twenty-two patients had normal prechemotherapy LBHT results. Two of these patients had abnormal post-chemotherapy LBHT results, which were associated with symptoms of lactose intolerance. CONCLUSION: Although chemotherapy may interfere with lactose metabolism, the development of symptomatic lactose intolerance is uncommon. Dietary restriction of milk products in patients receiving chemotherapy therefore is not warranted unless clinical symptoms of lactose intolerance are observed.", "conclusion": "Although chemotherapy may interfere with lactose metabolism, the development of symptomatic lactose intolerance is uncommon. Dietary restriction of milk products in patients receiving chemotherapy therefore is not warranted unless clinical symptoms of lactose intolerance are observed." }, { "pmid": "8003641", "year": 1994, "title": "A possible role for bile acid in the control of methanogenesis and the accumulation of hydrogen gas in the human colon.", "title_en": null, "title_de": "Eine mögliche Rolle von Gallensäure bei der Kontrolle der Methanogenese und der Akkumulation von Wasserstoffgas im menschlichen Kolon", "journal": "Journal of gastroenterology and hepatology", "authors": "Florin et al.", "author_search": "florin florin", "doi": "10.1111/j.1440-1746.1994.tb01228.x", "doi_url": "https://doi.org/10.1111/j.1440-1746.1994.tb01228.x", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/8003641/", "url": "https://h2medicine.org/studies/study-florin-1994-possible-bile-acid-control/", "methods": [ "inhalation" ], "indications": [ "sports-exercise" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "1994 · Florin — A Possible Role for Bile Acid in the Control of Methanogenesis and the Accumulation of Hydrogen Gas in the Human Colon", "summary": "This in-vitro study of anaerobic fecal cultures found that primary bile acids inhibit methanogenesis in a dose-dependent manner — suggesting that bile acids regulate the balance between H₂ accumulation and methane production in the human colon. High bile acid concentrations suppress methane-producing bacteria, leaving more H₂ to accumulate in the colon. (Journal of Gastroenterology and Hepatology, 1994.)", "assessment": "This is an in-vitro study on colonic microbiology — not a hydrogen therapy study. It is relevant to gut physiology, hydrogen breath testing, and the microbiome, but does not involve therapeutic H₂ administration. These results cannot be directly applied to human therapy. The hypothesis that bile acid–induced H₂ accumulation contributes to irritable bowel syndrome is speculative and requires in-vivo confirmation. The study was conducted in fecal cultures from only nine subjects (six non-methanogenic, three methanogenic), limiting its generalizability.", "abstract": "This study investigated a possible role for primary bile acid in the control of methanogenesis in the human colon. Production of hydrogen and methane was measured in anaerobic faecal cultures derived from faeces of six 'non-methanogenic' and three methanogenic healthy humans. Using a sensitive technique for gas measurement, methane was detected in all faecal cultures, including those from 'non-methanogenic' humans. Bile acid inhibited methanogenesis in a dose-response fashion in the in vitro 'non-methanogenic' and methanogenic faecal cultures. Inhibition was significant at bile acid concentrations > 0.05%. Methanogenesis correlated with methanogen (methanogenic bacteria) numbers. If this inhibition occurs in vivo, then it would explain much of the epidemiology of non-methanogenesis in humans. From an analysis of net hydrogen production by the faecal cultures, it is inferred that bile acid inhibits other hydrogen-consuming bacteria in addition to methanogens. These in vitro data suggest a major role for bile acid in the accumulation of hydrogen gas in the colon. Possible links between bile acid induced accumulation of gas and irritable bowel syndrome are discussed.", "conclusion": "These in vitro data suggest a major role for bile acid in the accumulation of hydrogen gas in the colon. Possible links between bile acid induced accumulation of gas and irritable bowel syndrome are discussed." }, { "pmid": "8041275", "year": 1994, "title": "Regeneration of functional hemoglobin from partially oxidized hemoglobin in the presence of molecular hydrogen and a multicomponent redox catalyst.", "title_en": null, "title_de": "Regeneration von funktionellem Hämoglobin aus teilweise oxidiertem Hämoglobin in Gegenwart von molekularem Wasserstoff und einem Mehrkomponenten-Redoxkatalysator", "journal": "Methods in enzymology", "authors": "McGown et al.", "author_search": "mcgown mc gown", "doi": "10.1016/0076-6879(94)31037-8", "doi_url": "https://doi.org/10.1016/0076-6879(94)31037-8", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/8041275/", "url": "https://h2medicine.org/studies/study-mcgown-1994-regeneration-functional-hemoglobin-partially/", "methods": [ "unspecified" ], "indications": [ "oxidative-stress" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "1994 · McGown — Regeneration of Functional Hemoglobin from Partially Oxidized Hemoglobin in the Presence of Molecular Hydrogen and a Multicomponent Redox Catalyst", "summary": "This in-vitro study demonstrated that molecular hydrogen (H₂) can reduce partially oxidized (met-)hemoglobin back to functional hemoglobin when a multicomponent redox catalyst is present — a proof-of-concept for H₂ as a biochemical reducing agent. No abstract is publicly available in the database record; details are accessible via the original publication. (Methods in Enzymology, 1994.)", "assessment": "This is an in-vitro biochemistry study demonstrating H₂ as a reducing agent for methemoglobin — not a therapeutic study. It is mechanistically interesting as an early demonstration of H₂ reactivity in biological molecules, but cannot serve as clinical evidence for therapeutic H₂. The use of an external multicomponent redox catalyst means the conditions are far from physiological. No abstract is available; a complete evaluation requires access to the original publication in Methods in Enzymology (1994).", "abstract": null, "conclusion": null }, { "pmid": "7949764", "year": 1994, "title": "Evaluation of tracheal mucosal blood flow during an extended radical operation for esophageal carcinoma: clinical and experimental studies.", "title_en": null, "title_de": "Beurteilung des trachealen Mukosa-Blutflusses während einer erweiterten Radikaloperation bei Ösophaguskarzinom", "journal": "Surgery today", "authors": "Nakahara et al.", "author_search": "nakahara nakahara", "doi": "10.1007/bf01833720", "doi_url": "https://doi.org/10.1007/bf01833720", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/7949764/", "url": "https://h2medicine.org/studies/study-nakahara-1994-tracheal-mucosal-blood-flow/", "methods": [], "indications": [ "cardiovascular", "cancer", "respiratory" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "tracer-clearance", "headline": "1994 · Nakahara et al. — Evaluation of tracheal mucosal blood flow during an extended radical operation for esophageal carcinoma", "summary": "Extended radical surgery for esophageal cancer significantly reduced tracheal mucosal blood flow, from 40 to 13 ml/100 g per minute, while preserving the right bronchial artery appeared protective. The hydrogen gas clearance method was used as a blood flow measurement tool during surgery — not as a therapeutic agent. (Surgery Today, 1994.)", "assessment": "Important context: this study does not investigate molecular hydrogen (H₂) as a therapeutic intervention. Hydrogen gas clearance is used as an intraoperative vascular physiology measurement technique. Additionally, the experimental component uses a dog model, with human data limited to 8 surgical patients. Limitations: small human cohort (n = 8), combined human/animal design, highly specialised surgical setting. Not relevant to H₂ therapy.", "abstract": "Using the hydrogen gas clearance method, a plate-type probe was attached to the surface of the cuff of an endotracheal tube in order to measure the ischemic changes in the tracheal mucosa produced by peritracheal lymph node dissection. In eight human subjects with intrathoracic esophageal carcinoma, the tracheal mucosal blood flow was 40.1 ml/100 g per minute after they had undergone a right thoracotomy and then decreased to 13.0 ml/100 g per minute after they had further received an extended radical operation preserving the right bronchial artery. No tracheal ulcers were seen. The same ischemic changes in the tracheal mucosa were also measured in dogs. The right bronchial artery contributes about one-third of the total blood flow to the trachea and this was thus calculated to be about 10-14 ml/100 g per minute.", "conclusion": "The same ischemic changes in the tracheal mucosa were also measured in dogs. The right bronchial artery contributes about one-third of the total blood flow to the trachea and this was thus calculated to be about 10-14 ml/100 g per minute." }, { "pmid": "8112709", "year": 1993, "title": "[Effect of endogenous opioids on gastric functions in man].", "title_en": null, "title_de": "Wirkung endogener Opioide auf die Magenfunktionen beim Menschen", "journal": "[Hokkaido igaku zasshi] The Hokkaido journal of medical science", "authors": "Suzuki", "author_search": "suzuki suzuki", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/8112709/", "url": "https://h2medicine.org/studies/study-suzuki-1993-endogenous-opioids-gastric-functions/", "methods": [], "indications": [ "neurology" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "tracer-clearance", "headline": "1993 · Suzuki — Effect of endogenous opioids on gastric functions in man", "summary": "Blocking endogenous opioids with naloxone reduced blood flow specifically in the gastric antrum — but not in the corpus — suggesting opioids regulate mucosal perfusion in a region-specific way. Hydrogen gas clearance was the blood flow measurement method, not a therapeutic agent. (Hokkaido Journal of Medical Science, 1993.)", "assessment": "Important context: this study does not investigate molecular hydrogen (H₂) as a therapeutic intervention. Inhaled hydrogen gas clearance is used as an intramucosal blood flow measurement technique — the standard regional vascular physiology tool of its era. The study topic is gastric neuroendocrine physiology. Design: controlled intravenous infusion protocol in healthy men with intramucosal hydrogen probes (n = 8–12 per endpoint). Limitations: small sample, single-site healthy male volunteers, pharmacological (not physiological) opioid blockade, mechanism conclusions are inferential. Not relevant to H₂ therapy.", "abstract": "Recent studies have demonstrated the presence of opioid peptides in the stomach, neurons of the vagus and the intrinsic nervous system. To evaluate the role of endogenous opioids on gastric mucosal blood flow, serum hormonal response, and gastric secretion, naloxone, a pure opioid antagonist, was infused or sprayed into healthy men, Furthermore, the effect of pentagastrin-induced gastric acid secretion on plasma beta-endorphin concentrations was investigated. Gastric mucosal blood flow was periodically determined by inhaled hydrogen gas clearance. The antrum and the corpus of the stomach could be investigated separately. Intravenous naloxone (40 micrograms/kg/hr) over 30 min caused a significant decline in the antral mucosal blood flow from 55.4 +/- 3.4 (mean +/- SE) ml/min/100 g before infusion to 47.2 +/- 3.0 ml/min/100 g 15 min after the start of injection (P < 0.05), and to 44.8 +/- 3.0 ml/min/100 g after 30 min (P < 0.05) (n = 12). Corresponding corpus mucosal blood flow did not change after infusion of naloxone (n = 8). No change occurred in the antral mucosal blood flow in response to naloxone spraying (0.6 mg) (n = 8). Intravenous administration of naloxone (40 micrograms/kg/hr) had no effect on serum gastrin and secretin concentrations or on the gastric acid secretion stimulated by pentagastrin (n = 8). The status of stimulated gastric acid secretion did not correlate with the release of plasma beta-endorphin. Since naloxone probably mirrors the action of endogenous opioids, these results indicate in humans that (1) endogenous opioids may be involved in the physiological regulation and augmentation of mucosal blood flow for the antrum, (2) the inhibitory effect of naloxone on gastric mucosal blood flow in the antrum does not seem to be mediated via opioid receptors of the mucosa, (3) endogenous opioids have no effect on basal acid secretion and acid secretion stimulated by pentagastrin, and (4) there is no interplay between acid secretion and plasma beta-endorphin.", "conclusion": "The status of stimulated gastric acid secretion did not correlate with the release of plasma beta-endorphin. Since naloxone probably mirrors the action of endogenous opioids, these results indicate in humans that (1) endogenous opioids may be involved in the physiological regulation and augmentation of mucosal blood flow for the antrum, (2) the inhibitory effect of naloxone on gastric mucosal bloo" }, { "pmid": "8249850", "year": 1993, "title": "Hydrogen inhalation for detecting intracardiac left-to-right shunting in adults.", "title_en": null, "title_de": "Wasserstoffinhalation zum Nachweis intrakardialer Links-Rechts-Shunts bei Erwachsenen", "journal": "The American journal of cardiology", "authors": "Glamann et al.", "author_search": "glamann glamann", "doi": "10.1016/0002-9149(93)90890-o", "doi_url": "https://doi.org/10.1016/0002-9149(93)90890-o", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/8249850/", "url": "https://h2medicine.org/studies/study-glamann-1993-inhalation-detecting-intracardiac-left/", "methods": [], "indications": [ "cardiovascular", "respiratory" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "tracer-clearance", "headline": "1993 · Glamann et al. — Hydrogen inhalation for detecting intracardiac left-to-right shunting in adults", "summary": "The hydrogen inhalation test reliably detected intracardiac left-to-right shunts in adults with perfect separation between the shunt and no-shunt groups (appearance times: 1.5 vs. 12 seconds). Hydrogen inhalation is used here as a sensitive diagnostic tracer — not as a therapeutic agent. The test eliminates the previous ambiguity of paediatric reference values when applied to adults. (American Journal of Cardiology, 1993.)", "assessment": "Important context: this study does not investigate molecular hydrogen (H₂) as a therapeutic intervention. Hydrogen inhalation is used exclusively as a diagnostic tracer in cardiac catheterisation to detect intracardiac shunts. This is one of the classic non-therapeutic clinical uses of H₂ — alongside the hydrogen clearance method for blood flow measurement. The study is prospective (n = 45 adults) with good diagnostic characterisation. Limitations: single-centre, no blinding described, no patients with very small shunts (Qp/Qs < 1.2) systematically included. Not relevant to H₂ therapy.", "abstract": "The hydrogen inhalation technique is easily performed and exquisitely sensitive for detecting intracardiac left-to-right shunting. Previous studies of this technique relied heavily on data from infants and children, and the distinction between \"normal\" and \"abnormal\" was imprecise and somewhat arbitrary. The present study was done to assess the results of hydrogen inhalation in adults with and without intracardiac left-to-right shunting. In 45 adult subjects (15 men, 30 women, aged 18 to 72 years) (18 without and 27 with intracardiac left-to-right shunting), the elapsed time from hydrogen inhalation to its appearance in the pulmonary artery was measured. The 18 patients without shunting had an appearance time of 12 +/- 3 (mean +/- SD) seconds, and it was > or = 9 seconds in all. In contrast, the 27 subjects with shunting had an appearance time of 1.5 +/- 0.7 second, with only 1 of 27 being > or = 3 seconds. There was no relation between the magnitude of left-to-right shunting and the hydrogen appearance time. Thus, the hydrogen inhalation technique easily and reliably separates adult subjects with and without intracardiac left-to-right shunting, with no overlap between the 2 groups.", "conclusion": "There was no relation between the magnitude of left-to-right shunting and the hydrogen appearance time. Thus, the hydrogen inhalation technique easily and reliably separates adult subjects with and without intracardiac left-to-right shunting, with no overlap between the 2 groups." }, { "pmid": "8357854", "year": 1993, "title": "A simplified method for deuterium/hydrogen isotope ratio measurements on water samples of biological origin.", "title_en": null, "title_de": "Eine vereinfachte Methode zur Messung des Deuterium/Wasserstoff-Isotopenverhältnisses an Wasserproben biologischen Ursprungs", "journal": "Biological mass spectrometry", "authors": "Scrimgeour et al.", "author_search": "scrimgeour scrimgeour", "doi": "10.1002/bms.1200220704", "doi_url": "https://doi.org/10.1002/bms.1200220704", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/8357854/", "url": "https://h2medicine.org/studies/study-scrimgeour-1993-simplified-method-deuterium-isotope/", "methods": [ "inhalation" ], "indications": [ "sports-exercise" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "1993 · Scrimgeour — A Simplified Method for Deuterium/Hydrogen Isotope Ratio Measurements on Water Samples of Biological Origin", "summary": "This methodological study describes an improved technique for measuring the deuterium-to-hydrogen (D/H or ²H/¹H) isotope ratio in biological water samples using platinum catalyst–driven equilibration in Vacutainers — enabling non-invasive assessment of total body water and water turnover in human studies. The method is especially suited for repeated studies without washout waiting periods. (Biological Mass Spectrometry, 1993.)", "assessment": "This is a methodological / analytical chemistry paper about stable isotope measurement — not a hydrogen therapy study. Deuterium (²H) is a stable hydrogen isotope used as a metabolic tracer; this paper has no relevance to therapeutic molecular H₂ administration. Its contribution lies in enabling more convenient total body water and energy expenditure measurements in nutritional research. Researchers seeking evidence on H₂ therapy will find nothing applicable here.", "abstract": "Equilibration of hydrogen gas with the water in a variety of biological sample materials was carried out in Vacutainers using platinum-on-alumina catalyst physically isolated from the liquid water. The equilibration takes 3 days at room temperature--much slower than with catalysts which float on the water surface--but this reduces the short-term temperature sensitivity of the procedure, and the inexpensive materials used allow convenient disposal of biologically contaminated samples after analysis. The slow equilibration also allows time for complete exchange with water contained in a complex sample matrix such as plant stems or soil without the need for prior isolation of the water sample. The method has particular application in studies of human total body water where repeated studies can be carried out over a short time period without the need to wait for the previous dose to wash out. Water turnover rates from total diurnal energy expenditure studies measured by this method were not significantly different from those obtained by the zinc reduction method.", "conclusion": "The method has particular application in studies of human total body water where repeated studies can be carried out over a short time period without the need to wait for the previous dose to wash out. Water turnover rates from total diurnal energy expenditure studies measured by this method were not significantly different from those obtained by the zinc reduction method." }, { "pmid": "1489103", "year": 1992, "title": "Regeneration of functional hemoglobin from iron(III) hemoglobin by reduction with hydrogen and a heterogeneous catalyst.", "title_en": null, "title_de": "Regeneration von funktionellem Hämoglobin aus Eisen(III)-Hämoglobin durch Reduktion mit Wasserstoff und einem heterogenen Katalysator", "journal": "Analytical biochemistry", "authors": "McGown et al.", "author_search": "mcgown mc gown", "doi": "10.1016/0003-2697(92)90505-2", "doi_url": "https://doi.org/10.1016/0003-2697(92)90505-2", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/1489103/", "url": "https://h2medicine.org/studies/study-mcgown-1992-regeneration-functional-hemoglobin-iron/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "1992 · McGown — Regeneration of Functional Hemoglobin from Iron(III) Hemoglobin by Reduction with Hydrogen and a Heterogeneous Catalyst", "summary": "This in-vitro study showed that molecular hydrogen (H₂), together with a heterogeneous platinum catalyst embedded in an electroactive polymer, can reduce methemoglobin (iron(III)-hemoglobin) back to functional iron(II) hemoglobin — restoring oxygen-binding capacity with cooperative binding characteristics comparable to native hemoglobin. The approach avoids protein adsorption problems of bare platinum and allows easy removal of catalyst and by-products. (Analytical Biochemistry, 1992.)", "assessment": "This is an in-vitro biochemistry study demonstrating H₂ as a reducing agent for methemoglobin — not a clinical or therapeutic study. The results confirm that H₂ can chemically reduce ferric hemoglobin under controlled in-vitro conditions, but these conditions are far from physiological and cannot be directly translated to human therapy. The study is historically interesting as an early demonstration of H₂ reactivity with biologically relevant iron-containing proteins. No therapeutic conclusions about H₂ supplementation should be drawn from this work.", "abstract": "Functional hemoglobin was regenerated from partially autoxidized hemoglobin by reduction with molecular hydrogen in the presence of a heterogeneous catalyst consisting of elemental platinum embedded in an electroactive polymer. The visible spectrum of the regenerated hemoglobin was identical to that of native iron(II) hemoglobin. The regenerated hemoglobin displayed highly cooperative oxygen-binding characteristics. P50 values for oxidized-regenerated hemoglobin samples were not different from native hemoglobin. The Hill coefficients for regenerated hemoglobin were slightly lower than the controls, possibly because of small amounts of irreversibly oxidized hemoglobin arising during the initial autoxidation. The advantages of the reduction system include: (1) the heterogeneous catalyst avoids the problem of protein adsorption onto bare platinum, (2) catalyst and reducing agent are easily removed from the protein, and (3) the by-product H+ is buffered easily.", "conclusion": "The Hill coefficients for regenerated hemoglobin were slightly lower than the controls, possibly because of small amounts of irreversibly oxidized hemoglobin arising during the initial autoxidation. The advantages of the reduction system include: (1) the heterogeneous catalyst avoids the problem of protein adsorption onto bare platinum, (2) catalyst and reducing agent are easily removed from the p" }, { "pmid": "1318087", "year": 1992, "title": "Crystallographic changes in calcium phosphates during plasma-spraying.", "title_en": null, "title_de": "Kristallographische Veränderungen in Calciumphosphaten während des Plasmaspritzens", "journal": "Biomaterials", "authors": "Ellies et al.", "author_search": "ellies ellies", "doi": "10.1016/0142-9612(92)90055-s", "doi_url": "https://doi.org/10.1016/0142-9612(92)90055-s", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/1318087/", "url": "https://h2medicine.org/studies/study-ellies-1992-crystallographic-changes-calcium-phosphates/", "methods": [ "inhalation" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "1992 · Ellies — Crystallographic Changes in Calcium Phosphates During Plasma-Spraying", "summary": "This in-vitro materials science study examined how plasma-spraying calcium phosphate powders — using hydrogen gas as part of the plasma torch process — causes crystallographic transformations, converting some hydroxyapatite (HA) to more-resorbable beta-tricalcium phosphate (β-TCP) and calcium oxide. Controlling the HA/β-TCP ratio on the coated surface may help tune the resorption rate of orthopedic and dental implant coatings. (Biomaterials, 1992.)", "assessment": "This is a materials science / biomaterials engineering study — not a hydrogen therapy study. Hydrogen gas appears only as a component of the plasma torch gas flow, not as a therapeutic agent. No conclusions about therapeutic H₂ can be drawn from this paper. The study is relevant to dental and orthopedic implant engineering, specifically to the design of calcium phosphate coatings with controlled resorption rates. Researchers in molecular hydrogen medicine will find nothing applicable here.", "abstract": "Coating hydroxyapatite (HA) onto metal implant surfaces using the plasma-spraying technique has been investigated in several laboratories as a means of improving the mechanical properties of the bulk ceramic. This study describes crystallographic changes which can occur during the plasma-spraying of calcium phosphate powders. A precipitated calcium-deficient apatite and a high temperature near-stoichiometric HA were each sprayed onto metal substrate in an argon plasma using several hydrogen gas flow conditions at various temperatures. The surfaces were examined by X-ray diffraction and scanning electron microscopy. The plasma-sprayed products were identified as a mixture of calcium phosphates including HA, beta-tricalcium phosphate (beta-TCP) and calcium oxide. Stoichiometric HA when plasma-sprayed showed the least (5%) degradation. Since beta-TCP is more resorbable than HA in vivo, varying the HA/beta-TCP ratio on the plasma-sprayed surface may provide a method to control surface dissolution of the coating.", "conclusion": "Stoichiometric HA when plasma-sprayed showed the least (5%) degradation. Since beta-TCP is more resorbable than HA in vivo, varying the HA/beta-TCP ratio on the plasma-sprayed surface may provide a method to control surface dissolution of the coating." }, { "pmid": "1313759", "year": 1992, "title": "A new zinc product for the reduction of water in physiological fluids to hydrogen gas for 2H/1H isotope ratio measurements.", "title_en": null, "title_de": "Ein neues Zinkprodukt zur Reduktion von Wasser in physiologischen Flüssigkeiten zu Wasserstoffgas für ²H/¹H-Isotopenverhältnis-Messungen", "journal": "European journal of clinical nutrition", "authors": "Wong et al.", "author_search": "wong wong", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/1313759/", "url": "https://h2medicine.org/studies/study-wong-1992-zinc-product-reduction-physiological/", "methods": [ "inhalation" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "1992 · Wong — A New Zinc Product for the Reduction of Water in Physiological Fluids to Hydrogen Gas for ²H/¹H Isotope Ratio Measurements", "summary": "This methodological study describes a new zinc-based reagent for converting water in physiological fluids to hydrogen gas for deuterium/hydrogen (²H/¹H) isotope ratio analysis — enabling accurate, convenient measurement of total body water and metabolic turnover rates in nutritional research. No abstract is publicly available; details are accessible via the original publication. (European Journal of Clinical Nutrition, 1992.)", "assessment": "This is a methodological / analytical chemistry paper on stable isotope analysis — not a hydrogen therapy study. Hydrogen gas is generated here solely as an analytical intermediate for mass spectrometric measurement of deuterium enrichment in body water. No implications for therapeutic molecular H₂ exist in this work. Its value is in nutritional and metabolic research methodology. Researchers seeking clinical evidence on H₂ therapy will find this paper entirely unrelated.", "abstract": null, "conclusion": null }, { "pmid": "1792946", "year": 1991, "title": "No evidence for an effect of lactase deficiency on bone mass in pre- or postmenopausal women.", "title_en": null, "title_de": "Kein Hinweis auf einen Effekt eines Lactasemangels auf die Knochenmasse bei prä- oder postmenopausalen Frauen", "journal": "Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research", "authors": "Slemenda et al.", "author_search": "slemenda slemenda", "doi": "10.1002/jbmr.5650061214", "doi_url": "https://doi.org/10.1002/jbmr.5650061214", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/1792946/", "url": "https://h2medicine.org/studies/study-slemenda-1991-evidence-lactase-deficiency-bone/", "methods": [], "indications": [ "metabolic", "womens-health" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "breath-test", "headline": "1991 · Slemenda et al. — No evidence for an effect of lactase deficiency on bone mass in pre- or postmenopausal women", "summary": "In 342 adult female twins, lactase deficiency showed no detectable negative effect on bone mass at any skeletal site. Interestingly, baseline exhaled hydrogen — a marker of gut bacterial activity — was positively associated with bone mass, independent of age. Breath hydrogen serves here as a diagnostic lactase-activity marker, not as a therapeutic agent. (Journal of Bone and Mineral Research, 1991.)", "assessment": "Important context: this study does not investigate molecular hydrogen (H₂) as a therapeutic intervention. Breath hydrogen is used as a diagnostic marker of lactase deficiency via the lactose breath hydrogen test — a standard gastroenterological screening tool. The study topic is bone metabolism and lactase genetics. Design: large twin study (n = 342), well-controlled for confounders. Limitations: cross-sectional design cannot establish causality; DZ twins only for discordant-pair analysis; the intriguing gut-bacteria/bone-mass association is exploratory and requires independent replication. Not relevant to H₂ therapy.", "abstract": "The potential role for lactase deficiency in the development of low bone mass was examined in 342 adult female twins. Diminished lactase activity, defined as greater than 20 ppm increase in expired hydrogen at 2 or 2.5 h after an oral lactose load, was examined: (1) by comparing bone mass between members of twin pairs discordant for lactase activity; (2) by examining the linear association between bone mass and total expired hydrogen gas; and (3) by comparing all lactase-deficient individuals to those with persistent lactase activity. Among members of discordant (primarily DZ) pairs, the lactase-deficient member had greater bone mass 54% of the time. The correlations between the increase in expired hydrogen and bone mass at various sites were between -0.02 (femoral neck) and 0.11 (midshaft radius), suggesting no association between these variables. Finally, all lactase-deficient subjects were compared with those with normal lactase activity, regardless of twin status, and at each skeletal site the differences in bone mass were 1% or less. Thus, all primary hypotheses were not supported by these data; that is, in this large sample we could find no evidence of a detrimental effect of lactase deficiency on adult bone mass. However, baseline expired hydrogen was consistently and positively associated with bone mass at all sites, independently of age, suggesting the possibility that some aspect of intestinal function related to the activity of bacterial anaerobes may be positively associated with bone mass.", "conclusion": "Thus, all primary hypotheses were not supported by these data; that is, in this large sample we could find no evidence of a detrimental effect of lactase deficiency on adult bone mass. However, baseline expired hydrogen was consistently and positively associated with bone mass at all sites, independently of age, suggesting the possibility that some aspect of intestinal function related to the acti" }, { "pmid": "1651893", "year": 1991, "title": "[Protective effect of rebamipide (OPC-12759) on the gastric mucosa in rats and humans].", "title_en": null, "title_de": "Schützende Wirkung von Rebamipid (OPC-12759) auf die Magenschleimhaut bei Ratten und Menschen", "journal": "Nihon yakurigaku zasshi. Folia pharmacologica Japonica", "authors": "Kawano et al.", "author_search": "kawano kawano", "doi": "10.1254/fpj.97.6_371", "doi_url": "https://doi.org/10.1254/fpj.97.6_371", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/1651893/", "url": "https://h2medicine.org/studies/study-kawano-1991-protective-rebamipide-opc-12759/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "1991 · Kawano — Protective Effect of Rebamipide (OPC-12759) on the Gastric Mucosa in Rats and Humans", "summary": "This combined animal and small human study showed that rebamipide — a gastric mucosal protective drug — prevents HCl-ethanol-induced gastric lesions in rats dose-dependently and significantly inhibits mucosal damage in healthy human volunteers, partly by improving mucosal microcirculation as measured by hydrogen gas clearance. The hydrogen gas clearance method is used here as a blood-flow measurement tool, not as a therapy. (Nihon Yakurigaku Zasshi / Folia Pharmacologica Japonica, 1991.)", "assessment": "This is a mixed animal and small human study on the gastroprotective drug rebamipide — not a hydrogen therapy study. Hydrogen gas appears only as a measurement tool (mucosal blood flow via H₂ clearance), not as a therapeutic agent. No conclusions about molecular H₂ therapy can be drawn from this paper. The human component involves only 6 healthy volunteers with experimentally induced gastric damage — results should be interpreted cautiously. The study is relevant to gastroenterological pharmacology, not to hydrogen medicine.", "abstract": "The protective effect of rebamipide against 0.15 N HCl solution containing 40% ethanol (HCl-ethanol)-induced mucosal lesion in the stomach was evaluated in rats and humans. In rat experiments: (1) rebamipide prevented development of mucosal damage induced by HCl-ethanol in a dose-dependent manner when tested at 10, 30, 100 and 300 mg/kg, i.p., and the prevention at 30-300 mg/kg was significant (P less than 0.05); (2) rebamipide significantly (P less than 0.05) increased mucosal blood flow by continuous i.v. dosing at 10 mg/kg/hr by the hydrogen gas clearance method; (3) rebamipide at 10 mg/kg, i.v., also significantly (P less than 0.05) inhibited reduction in gastric mucosal blood volume and tended to suppress oxygen saturation of hemoglobin following hemorrhagic shock by organ reflectance spectrophotometry. A double-blind crossover study was conducted to compare the gastric protective effect of rebamipide with an inactive placebo using 6 healthy male volunteers. Rebamipide was administered to them at a clinical dose of 300 mg/day orally for 7 days, and then HCl-ethanol was given once to induce mucosal damage. Rebamipide significantly (P less than 0.05) inhibited formation of mucosal lesion, decrease in the number of mucous granules and dilatation of intercellular space. These clinical findings indicate that rebamipide was protective against HCl-ethanol-induced gastric lesion at a clinical dose, and the mechanism of this gastric effect was considered to involve, in part, the improvement of mucosal microcirculation.", "conclusion": "Rebamipide significantly (P less than 0.05) inhibited formation of mucosal lesion, decrease in the number of mucous granules and dilatation of intercellular space. These clinical findings indicate that rebamipide was protective against HCl-ethanol-induced gastric lesion at a clinical dose, and the mechanism of this gastric effect was considered to involve, in part, the improvement of mucosal micro" }, { "pmid": "2379871", "year": 1990, "title": "Alternative pathways for hydrogen disposal during fermentation in the human colon.", "title_en": null, "title_de": "Alternative Wege zur Wasserstoffbeseitigung während der Fermentation im menschlichen Kolon.", "journal": "Gut", "authors": "Gibson et al.", "author_search": "gibson gibson", "doi": "10.1136/gut.31.6.679", "doi_url": "https://doi.org/10.1136/gut.31.6.679", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/2379871/", "url": "https://h2medicine.org/studies/study-gibson-1990-alternative-pathways-disposal-during/", "methods": [ "inhalation" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "1990 · Gibson — Alternative pathways for hydrogen disposal during fermentation in the human colon.", "summary": "When gut bacteria ferment carbohydrates, they produce hydrogen gas that must be disposed of — and the colon has several competing routes for doing so. This in-vitro study with stool samples from 30 healthy adults found that methanogenesis was the dominant disposal pathway in most people, while sulphate reduction dominated in a minority — with both processes appearing mutually exclusive. (Gut, 1990.)", "assessment": "This is a foundational in-vitro microbiology study — not a therapeutic investigation. It helps explain why breath hydrogen tests show wide inter-individual variation: some people are „methane producers“, others are „sulphate reducers“, and only a small fraction excretes large amounts of H₂ in breath. Limitation: stool slurry experiments do not fully replicate in-vivo colonic conditions. The study provides mechanistic context for hydrogen metabolism in the gut but offers no evidence on therapeutic H₂ use in humans or animals.", "abstract": "Hydrogen gas, which is produced during fermentation in the human colon, is either excreted in breath or metabolised by gut bacteria through a variety of pathways. These may include methanogenesis, dissimilatory sulphate reduction, and acetogenesis. To determine which of these routes predominates in the large intestine, stools were taken from 30 healthy subjects and incubated as 5% (w/v) slurries with Lintner's starch. In 23 of 30 subjects, methane production was the main method of hydrogen disposal. In the remaining seven, high rates of sulphate reduction were recorded together with raised production of H2S. All samples showed relatively low rates of hydrogen evolution and of acetate formation from CO2 and H2. Sulphate reduction and methanogenesis seem to be mutually exclusive in the colon and this is probably linked to sulphate availability. Sulphate reduction, methanogenesis, and acetogenesis were strongly influenced by pH. Sulphate reduction was optimal at alkaline pH values whereas methane production was maximal at a neutral pH and acetogenesis favoured acidic conditions. Faecal H2S values were related to carriage of sulphate reducing bacteria. These data show that a number of competing pathways for hydrogen disposal are possible in the large gut and that a variety of factors such as colonic pH and sulphate availability can determine which of these mechanisms predominates.", "conclusion": "Faecal H2S values were related to carriage of sulphate reducing bacteria. These data show that a number of competing pathways for hydrogen disposal are possible in the large gut and that a variety of factors such as colonic pH and sulphate availability can determine which of these mechanisms predominates." }, { "pmid": "2191785", "year": 1990, "title": "Assessment of the sensitivity of hydrogen inhalation in the detection of left-to-right shunting.", "title_en": null, "title_de": "Beurteilung der Sensitivität der Wasserstoffinhalation beim Nachweis von Links-Rechts-Shunts", "journal": "Catheterization and cardiovascular diagnosis", "authors": "Flores et al.", "author_search": "flores flores", "doi": "10.1002/ccd.1810200206", "doi_url": "https://doi.org/10.1002/ccd.1810200206", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/2191785/", "url": "https://h2medicine.org/studies/study-flores-1990-sensitivity-inhalation-detection-left/", "methods": [], "indications": [ "cardiovascular", "respiratory" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "tracer-clearance", "headline": "1990 · Flores et al. — Assessment of the Sensitivity of Hydrogen Inhalation in the Detection of Left-to-Right Shunting", "summary": "Inhaling a small amount of hydrogen gas and measuring its reappearance on the arterial side of the circulation is an extremely sensitive method for detecting left-to-right intracardiac shunts — far more sensitive than standard dye or oximetry techniques. In 15 patients, artificially created shunts as small as 0.7 % were reliably detected. The clinical value: earlier and more accurate diagnosis of congenital or acquired cardiac defects. (Catheterization and Cardiovascular Diagnosis, 1990.)", "assessment": "Important note on scope: This is a diagnostic study, not a therapeutic H₂ study. H₂ is used here purely as an inert tracer gas to visualise cardiac shunts — no antioxidant, anti-inflammatory, or metabolic effect is investigated. The study is methodologically solid (n = 15, controlled artificial shunts with known sizes, simultaneous thermodilution reference), but it contributes nothing to the question of H₂ as a health intervention. Limitations: small n; exclusively diagnostic endpoint; results cannot be extrapolated to therapeutic H₂ inhalation at higher concentrations or longer durations.", "abstract": "For the detection of left-to-right intracardiac shunting, the oximetric and standard indocyanine green techniques are relatively insensitive, in that neither can reliably detect a shunt with a ratio of pulmonary to systemic flow (Qp/Qs) less than 1.3 (percentage shunt, 23%). Although the hydrogen inhalation method is said to be much more sensitive in this regard, no previous study has measured its sensitivity. Accordingly, in 15 patients (4 men, 11 women, aged 38 to 67 years) without intracardiac shunting, hydrogen inhalation was performed 1) without and 2) with an artificially created femoral arteriovenous shunt of known size, and cardiac output was measured by thermodilution. For the 15 subjects with cardiac outputs of 3.64 to 8.10 liters/min, shunts of 22 to 248 ml/min were created, so that the shunts ranged from 0.5% to 3.3%. Hydrogen inhalation detected all shunts greater than or equal to 1.3% (Qp/Qs greater than or equal to 1.01). Of the 10 shunts less than 1.3%, it detected 5, with the smallest being 0.7%. Thus, the hydrogen inhalation technique is extremely sensitive in identifying the presence of left-to-right shunting, far more sensitive than the oximetric and standard indocyanine green methods.", "conclusion": "Of the 10 shunts less than 1.3%, it detected 5, with the smallest being 0.7%. Thus, the hydrogen inhalation technique is extremely sensitive in identifying the presence of left-to-right shunting, far more sensitive than the oximetric and standard indocyanine green methods." }, { "pmid": "2365796", "year": 1990, "title": "[Measurement of hepatic blood flow by the hydrogen gas clearance method. Experimental and clinical observations].", "title_en": null, "title_de": "Messung des hepatischen Blutflusses mittels Wasserstoffgas-Clearance-Methode: Experimentelle und klinische Beobachtungen", "journal": "Nihon Ika Daigaku zasshi", "authors": "Makino", "author_search": "makino makino", "doi": "10.1272/jnms1923.57.137", "doi_url": "https://doi.org/10.1272/jnms1923.57.137", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/2365796/", "url": "https://h2medicine.org/studies/study-makino-1990-measurement-hepatic-blood-flow/", "methods": [], "indications": [ "liver", "sports-exercise", "cancer" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "tracer-clearance", "headline": "1990 · Makino — Measurement of Hepatic Blood Flow by the Hydrogen Gas Clearance Method: Experimental and Clinical Observations", "summary": "Inhaled hydrogen gas serves as a highly accurate and minimally invasive tool for measuring liver blood flow in real time. In both animal experiments and patients with various liver diseases, the H₂ clearance method correlated closely with established reference techniques and revealed characteristic blood-flow patterns in hepatitis, cirrhosis, fatty liver, and liver tumours. (Nihon Ika Daigaku Zasshi, 1990.)", "assessment": "Important note on scope: This is a diagnostic methodology study, not a therapeutic H₂ study. Hydrogen gas is used solely as an inert tracer for blood-flow measurement — no antioxidant or anti-inflammatory therapeutic intent is present. The study includes both animal experiments (rabbits, carbon-tetrachloride-treated rats) and human patients; the human clinical portion covers liver diseases. Methodologically solid, though sample sizes per subgroup are not specified in the abstract. Limitations: no therapeutic H₂ endpoint; mixed animal/human design; the clinical sections lack precise n values per disease category.", "abstract": "In this study, the author intended to examine the validity of the inhaled hydrogen gas clearance method (i-H2) for determination of the hepatic blood flow (HBF), and also to show some applicabilities of the method in experimental animals and patients with liver diseases. Simultaneous determinations of HBF by i-H2 and electromagnetic flowmetry in rabbits revealed an excellent correlation between the values obtained by the two methods. Moreover, HBF in rabbits measured by i-H2 varied in parallel with that by thermocouple flowmetry or laser Doppler velocimetry after administration of norepinephrine, propranolol or glucagon. In carbon tetrachloride-treated rats, HBF measured by i-H2 correlated better with the severity of damage in the sinusoidal structure than the severity of hepatic cell injury or the serum levels of transaminases. HBF as determined by i-H2 was significantly decreased in acute hepatitis (AH), chronic inactive hepatitis (CIH), chronic active hepatitis (CAH), liver cirrhosis (LC) and fatty liver. Reduced HBF in AH returned to normal during recovery of the disease. The ratio of HBF in tumor/normal tissue was greater than 1.0 for hepatocellular carcinoma in contrast to the ratio of less than 1.0 for metastatic liver carcinoma. Propranolol caused a decrease in HBF by 31%, and vasopressin by 39% in patients with CIH or LC. In contrast, glucagon induced its increase by 65%, 35% and 17%, respectively, in patients with CIH, AH and LC.", "conclusion": "Propranolol caused a decrease in HBF by 31%, and vasopressin by 39% in patients with CIH or LC. In contrast, glucagon induced its increase by 65%, 35% and 17%, respectively, in patients with CIH, AH and LC." }, { "pmid": "2314375", "year": 1990, "title": "[Correlation between gastric microcirculation and mucosal injury after surgical therapy of esophageal varices].", "title_en": null, "title_de": "Korrelation zwischen gastraler Mikrozirkulation und Mukosaschädigung nach chirurgischer Therapie von Ösophagusvarizen.", "journal": "Nihon Geka Gakkai zasshi", "authors": "Mitarai et al.", "author_search": "mitarai mitarai", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/2314375/", "url": "https://h2medicine.org/studies/study-mitarai-1990-correlation-between-gastric-microcirculation/", "methods": [ "inhalation" ], "indications": [ "cardiovascular" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "1990 · Mitarai — Correlation between gastric microcirculation and mucosal injury after surgical therapy of esophageal varices.", "summary": "Surgery for esophageal varices can substantially reduce blood flow to the stomach lining, and the degree of this reduction correlates directly with post-operative mucosal damage. This animal study used hydrogen gas clearance — a blood flow measurement technique — to show that transection surgery cuts gastric mucosal flow by up to 30%, while a shunt procedure preserves it much better. (Nihon Geka Gakkai zasshi, 1990.)", "assessment": "This is an animal/clinical observation study using H₂ gas purely as a blood-flow measurement tracer — there is no therapeutic H₂ application. The finding that >20% reduction in mucosal flow predicts post-operative mucosal injury is clinically relevant for surgical planning. Important context for H₂ research: the hydrogen gas clearance method was a widely-used flow measurement technique in the 1980s–90s; this paper belongs to that methodological tradition, not to molecular hydrogen therapy research.", "abstract": "The correlation between gastric microcirculation and mucosal injury was studied in patients who underwent surgery for esophageal varices. Both mucosal and submucosal blood flow at the lower esophagus, gastric body and antrum was measured using hydrogen gas clearance method through endoscopy in 55 patients including 33 cirrhotics, 10 idiopathic portal hypertensive patients and 12 controls. In 20 cases with esophageal varices, 10 patients were treated with transabdominal esophageal transection (transection group) and 10 with left gastric vena caval shunt (shunt group). The patients with portal hypertension, showed a reduced blood flow in gastric mucosa but increased flow in the submucosa, as compared with the controls. When comparing the postoperative changes in gastric mucosal flow between the two groups, the transection group showed a reduction of mucosal flow by approximately 30% during surgery, and 20% for 4 weeks after operation. In shunt group, the mucosal flow was well preserved with reduction rate less than 10%. Postoperative mucosal injury was endoscopically and histologically found in almost all patients who showed a reduction rate of more than 20%. This study suggests that active protection against possible gastric mucosal lesion should be kept in mind in the setting of surgical therapy for esophageal varices.", "conclusion": "Postoperative mucosal injury was endoscopically and histologically found in almost all patients who showed a reduction rate of more than 20%. This study suggests that active protection against possible gastric mucosal lesion should be kept in mind in the setting of surgical therapy for esophageal varices." }, { "pmid": "2666015", "year": 1989, "title": "Effects of Escherichia coli spheroplast formation on assays of H2 and adenosine triphosphate based ampicillin susceptibility tests.", "title_en": null, "title_de": "Auswirkungen der Sphäroplastenbildung von Escherichia coli auf H₂- und Adenosintriphosphat-basierte Ampicillin-Empfindlichkeitstests.", "journal": "Diagnostic microbiology and infectious disease", "authors": "Hörnsten et al.", "author_search": "hörnsten hörnsten", "doi": "10.1016/0732-8893(89)90009-6", "doi_url": "https://doi.org/10.1016/0732-8893(89)90009-6", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/2666015/", "url": "https://h2medicine.org/studies/study-hoernsten-1989-escherichia-coli-spheroplast-formation/", "methods": [ "unspecified" ], "indications": [ "sports-exercise" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "1989 · Hörnsten — Effects of Escherichia coli spheroplast formation on assays of H₂ and adenosine triphosphate based ampicillin susceptibility tests.", "summary": "When the antibiotic ampicillin damages the cell walls of E. coli bacteria, forming spheroplasts, the bacteria's hydrogen production drops — but their ATP levels remain relatively normal, creating a discrepancy between two different antibiotic susceptibility testing methods. This in-vitro microbiology study investigated how spheroplast formation affects the reliability of H₂-based and ATP-based bacterial susceptibility assays. (Diagnostic Microbiology and Infectious Disease, 1989.)", "assessment": "This is a methodological in-vitro microbiology study. Hydrogen here is a bacterial metabolite used as a diagnostic readout — there is no connection to molecular hydrogen therapy. The paper is of interest in the context of antibiotic susceptibility testing methodology but is not relevant to the question of H₂ as a therapeutic agent in humans or animals.", "abstract": "The present study examined the effects of ampicillin on one strain of Escherichia coli in lactose peptone broth with an osmolality of 342 mosm/L under anaerobic conditions. Spheroplast formation occurred at 10 X MIC of ampicillin. The metabolic changes that took place during spheroplast formation disfavored the production of molecular hydrogen. The intracellular bacterial adenosine triphosphate (ATP) level remained normal or slightly elevated during spheroplast formation while viability (cfu/ml) decreased. Thus spheroplast formation did not interfere significantly with ampicillin susceptibility as interpreted by assaying molecular hydrogen and viability. The effect on the ATP assay was, however, pronounced. It was found that the reversion of spheroplasts to bacterial cells for this particular strain (as recorded by cfu/ml) did not occur in quantitative numbers. The ATP assay thus indicated an approximate of the density of cells, while viability studies reported a lower cell density. When using a broth with lower osmolality (50 mosm/L) no spheroplast formation occurred and a close relation between viability and intracellular ATP was observed.", "conclusion": "The ATP assay thus indicated an approximate of the density of cells, while viability studies reported a lower cell density. When using a broth with lower osmolality (50 mosm/L) no spheroplast formation occurred and a close relation between viability and intracellular ATP was observed." }, { "pmid": "2496538", "year": 1989, "title": "GasPak Plus versus Anaerocult A--two carbon dioxide/hydrogen systems for cultivation of anaerobes.", "title_en": null, "title_de": "GasPak Plus versus Anaerocult A – zwei Kohlendioxid/Wasserstoff-Systeme zur Kultivierung von Anaerobiern.", "journal": "Zentralblatt fur Bakteriologie, Mikrobiologie, und Hygiene. Series A, Medical microbiology, infectious diseases, virology, parasitology", "authors": "Heizmann et al.", "author_search": "heizmann heizmann", "doi": "10.1016/s0176-6724(89)80022-7", "doi_url": "https://doi.org/10.1016/s0176-6724(89)80022-7", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/2496538/", "url": "https://h2medicine.org/studies/study-heizmann-1989-gaspak-plus-versus-anaerocult/", "methods": [ "inhalation" ], "indications": [ "metabolic", "sports-exercise", "neurology", "cardiovascular" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "1989 · Heizmann — GasPak Plus versus Anaerocult A — two carbon dioxide/hydrogen systems for cultivation of anaerobes.", "summary": "Two commercially available CO₂/H₂ gas-generating systems for culturing anaerobic bacteria were compared and found to be equally effective overall, though growth varied considerably between individual bacterial species. This in-vitro laboratory study tested 80 strains of 28 anaerobic species relevant to clinical diagnostics. (Zentralblatt für Bakteriologie, Mikrobiologie, und Hygiene, 1989.)", "assessment": "This is a technical in-vitro microbiology study comparing two laboratory culture systems. H₂ gas here serves as a chemical reducing agent to maintain anaerobic conditions — it has no therapeutic role. The paper is relevant for clinical microbiology laboratories but has no bearing on molecular hydrogen therapy research.", "abstract": "Two disposable carbon dioxide/hydrogen gas-generating systems (GasPak Plus and Anaerocult A) were compared by assessing growth of obligate anaerobic bacteria. Eighty strains representing 28 species of anaerobic bacteria commonly occurring at various body sites were seeded onto 4 brain heart chocolate agar plates using a spiral plater; and 1 plate each was subsequently incubated in 2 Anaerocult A and 2 GasPak Plus systems. Bacterial growth was expressed as colony-forming units per ml (CFU/ml), reproducibility of the seeding procedure was checked, and the potential interference of H2S-producing bacteria with operation of the carbon dioxide/hydrogen systems was investigated. The presence of H2S only inhibited bacterial growth in the case of Peptostreptococcus asaccharolyticus - an effect observed in both systems. Reproducibility of the seeding procedure using the spiral plater was within acceptable range. Differences between the systems were not apparent when comparing total CFU/ml of a given species and the systems therefore provide equally effective environments for incubation of anaerobic bacteria. In both systems, however, growth varied from one species or strain to another. In mixed infections, detection of certain species of anaerobes may therefore be difficult using either system.", "conclusion": "In both systems, however, growth varied from one species or strain to another. In mixed infections, detection of certain species of anaerobes may therefore be difficult using either system." }, { "pmid": "3140651", "year": 1988, "title": "The acceptability of milk and milk products in populations with a high prevalence of lactose intolerance.", "title_en": null, "title_de": "Die Akzeptanz von Milch und Milchprodukten in Bevölkerungsgruppen mit hoher Prävalenz von Lactoseintoleranz.", "journal": "The American journal of clinical nutrition", "authors": "Scrimshaw et al.", "author_search": "scrimshaw scrimshaw", "doi": "10.1093/ajcn/48.4.1142", "doi_url": "https://doi.org/10.1093/ajcn/48.4.1142", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/3140651/", "url": "https://h2medicine.org/studies/study-scrimshaw-1988-acceptability-milk-milk-products/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "other" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "1988 · Scrimshaw — The acceptability of milk and milk products in populations with a high prevalence of lactose intolerance.", "summary": "Most humans lose the ability to digest lactose after infancy — and a standard lactose tolerance test is a poor predictor of whether an individual can actually consume moderate amounts of milk without symptoms. This review explains the global prevalence of lactose maldigestion, the role of hydrogen gas in breath testing for diagnosis, and why fermented dairy products are often better tolerated. (The American Journal of Clinical Nutrition, 1988.)", "assessment": "This is a narrative review on lactose intolerance, using H₂ breath testing as a diagnostic tool — there is no therapeutic H₂ application. The paper is a high-quality public health overview that established important principles about the gap between laboratory lactose testing and real-world dairy tolerance. Its connection to molecular hydrogen research is purely methodological: breath H₂ here is a marker of malabsorption, not a therapeutic molecule.", "abstract": "1) Most humans, like other mammals, gradually lose the intestinal enzyme lactase after infancy and with it the ability to digest lactose, the principle sugar in milk. At some point in prehistory, a genetic mutation occurred and lactase activity persisted in a majority of the adult population of Northern and Central Europe. 2) Persistence of intestinal lactase, the uncommon trait worldwide, is inherited as a highly penetrant autosomal-dominant characteristic. Both types of progeny are almost equally common when one parent is a lactose maldigester and the other a lactose digester. 3) The incidence of lactose maldigestion is usually determined in adults by the administration in the fasting state of a 50-g dose of lactose in water, the equivalent of that in 1 L of milk. Measurement is made of either the subsequent rise in blood glucose or the appearance of additional hydrogen in the breath. It is also sometimes identified by measuring lactase activity directly in a biopsy sample from the jejunum. For children the test dose is reduced according to weight. Depending on the severity of the lactase deficiency and other factors, the test dose may result in abdominal distention, pain, and diarrhea. 4) The frequency of lactose maldigestion varies widely among populations but is high in nearly all but those of European origin. In North American adults lactose maldigestion is found in approximately 79% of Native Americans, 75% of blacks, 51% of Hispanics, and 21% of Caucasians. In Africa, Asia, and Latin America prevalence rates range from 15-100% depending on the population studied. 5) Whenever the lactose ingested exceeds the capacity of the intestinal lactase to split it into the simple sugars glucose and galactose, which are absorbed directly, it passes undigested to the large intestine. There it is fermented by the colonic flora, with short-chain fatty acids and hydrogen gas as major products. The gas produced can cause abdominal distention and pain and diarrhea may also result from the fermentation products. 6) Among individuals with incomplete lactose digestion, there is considerable variation in awareness of lactose intolerance and in the quantity of lactose that can be ingested without symptoms. A positive standard lactose test is not a reliable predictor of the ability of an individual to consume moderate amounts of milk and milk products without symptoms. In usual situations the quantity of lactose ingested at any one time is much less than in the lactose-tolerance test.(ABSTRACT TRUNCATED AT 400 WORDS)", "conclusion": "A positive standard lactose test is not a reliable predictor of the ability of an individual to consume moderate amounts of milk and milk products without symptoms. In usual situations the quantity of lactose ingested at any one time is much less than in the lactose-tolerance test.(ABSTRACT TRUNCATED AT 400 WORDS)" }, { "pmid": "2831734", "year": 1988, "title": "Role of blood flow in gastric acid secretion.", "title_en": null, "title_de": "Rolle des Blutflusses bei der Magensäuresekretion.", "journal": "The American journal of physiology", "authors": "Holm et al.", "author_search": "holm holm", "doi": "10.1152/ajpgi.1988.254.3.g281", "doi_url": "https://doi.org/10.1152/ajpgi.1988.254.3.g281", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/2831734/", "url": "https://h2medicine.org/studies/study-holm-1988-blood-flow-gastric-acid/", "methods": [ "inhalation", "drinking-hrw" ], "indications": [ "other" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "1988 · Holm — Role of blood flow in gastric acid secretion.", "summary": "The relationship between blood flow and gastric acid secretion is more complex than long assumed: most measurement methods show no simple proportional link, but there is a critical minimum blood flow below which both oxygen use and acid secretion fall together. This review critically evaluates multiple blood flow measurement techniques — including hydrogen gas clearance — used to study gastric physiology. (The American Journal of Physiology, 1988.)", "assessment": "This is a critical narrative review of gastric physiology methods. Hydrogen gas clearance is evaluated here as one of several blood flow measurement techniques — it is not being studied as a therapeutic agent. The review has no direct relevance to molecular hydrogen therapy; its value is in understanding how gastric blood flow was historically measured and what the true relationship between perfusion and acid secretion looks like.", "abstract": "The relationship between gastric acid secretion and blood flow has been investigated with a variety of different blood flow techniques including aminopyrine clearance, hydrogen gas clearance, intravital microscopy, laser-Doppler flowmetry, radioactive microspheres, and the elimination of inert gases. The most commonly used technique, aminopyrine clearance, predicts that increasing acid secretion is accompanied by a parallel increase in blood flow. However, the efficiency of clearance of aminopyrine is low in the nonsecreting stomach and increases as secretion rate increases. This precludes the use of aminopyrine clearance as a reliable measure of gastric mucosal blood flow at all but the highest steady-state level of acid secretion and casts doubt on the findings with this technique. Other methods for measuring blood flow indicate that there is no simple relationship between secretion and flow, with some studies finding that secretion and flow change in parallel and others finding that secretion varies quite independently of flow to the mucosa. One consistent finding is a strong correlation between stimulated acid secretion and gastric oxygen consumption. Both acid secretion and oxygen consumption fall if celiac blood flow is reduced below a critical value, which in the anesthetized dog stomach is approximately 30-40 ml.min-1.100 g-1. Driving blood flow above this value does not increase oxygen consumption and acid secretion, i.e., they reach a plateau. The shape of this relationship with its flow-dependent and flow-independent portions is used to explain the apparently contradictory findings in the literature regarding gastric acid secretion and blood flow.", "conclusion": "Driving blood flow above this value does not increase oxygen consumption and acid secretion, i.e., they reach a plateau. The shape of this relationship with its flow-dependent and flow-independent portions is used to explain the apparently contradictory findings in the literature regarding gastric acid secretion and blood flow." }, { "pmid": "2849711", "year": 1988, "title": "Dietary fibre and health: the role of hydrogen production.", "title_en": null, "title_de": "Ballaststoffe und Gesundheit: die Rolle der Wasserstoffproduktion", "journal": "Medical hypotheses", "authors": "Neale", "author_search": "neale neale", "doi": "10.1016/0306-9877(88)90091-6", "doi_url": "https://doi.org/10.1016/0306-9877(88)90091-6", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/2849711/", "url": "https://h2medicine.org/studies/study-neale-1988-dietary-fibre-health-production/", "methods": [], "indications": [ "skin-aging", "oxidative-stress" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "byproduct", "headline": "1988 · Neale — Dietary Fibre and Health: The Role of Hydrogen Production", "summary": "A hypothesis paper proposing that molecular hydrogen, produced in large amounts during gut fermentation of dietary fibre, may be a key mediator of fibre's protective health effects — acting as a natural antioxidant against damaging free radicals in body tissues. This early 1988 work predates the modern H₂ therapy field by nearly two decades, yet anticipates its central mechanism. (Medical Hypotheses, 1988.)", "assessment": "This is a hypothesis paper with no primary data — no clinical trial, no animal experiment, no in-vitro assay is presented. Its value is purely conceptual and historical: it correctly anticipated the selective antioxidant hypothesis of H₂ that became the foundation of modern H₂ medicine. It should be cited as conceptual background, not as evidence. Limitations: no experimental data; speculative by design; the proposed mechanism (reduction of singlet oxygen by H₂ in tissues) was not directly tested here; the paper does not distinguish between endogenously produced H₂ and exogenously administered H₂.", "abstract": "The biological basis for the epidemiological association between high dietary fibre intakes and reduced disease incidence in Man is not fully understood. It is proposed that molecular hydrogen, produced in quite large amounts as a by-product of colonic fermentation of dietary fibre and unabsorbed carbohydrate may play an important role. Hydrogen in the tissues may act as a powerful reducing agent (antioxidant) of potentially damaging free radical species (e.g. singlet oxygen) and in so doing, along with other antioxidants would help in the control of these potentially damaging species and their known involvement in disease causation.", "conclusion": "Hydrogen in the tissues may act as a powerful reducing agent (antioxidant) of potentially damaging free radical species (e.g. singlet oxygen) and in so doing, along with other antioxidants would help in the control of these potentially damaging species and their known involvement in disease causation." }, { "pmid": "3132563", "year": 1988, "title": "Effect of endocrine treatment on prostatic blood flow in patients with prostatic adenocarcinoma.", "title_en": null, "title_de": "Wirkung einer endokrinen Behandlung auf den prostatischen Blutfluss bei Patienten mit prostatischem Adenokarzinom", "journal": "The Journal of urology", "authors": "Toma et al.", "author_search": "toma toma", "doi": "10.1016/s0022-5347(17)41495-9", "doi_url": "https://doi.org/10.1016/s0022-5347(17)41495-9", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/3132563/", "url": "https://h2medicine.org/studies/study-toma-1988-endocrine-prostatic-blood-flow/", "methods": [], "indications": [ "neurology", "cancer" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "tracer-clearance", "headline": "1988 · Toma et al. — Effect of Endocrine Treatment on Prostatic Blood Flow in Patients with Prostatic Adenocarcinoma", "summary": "In 19 patients with prostatic adenocarcinoma, hydrogen gas clearance measurements showed that endocrine (hormone) therapy significantly increased blood flow to the prostate while reducing tumour volume — a finding suggesting that enhanced perfusion accompanies tumour cell deterioration under hormonal treatment. This is a diagnostic blood-flow measurement study, not an H₂ therapy study. (The Journal of Urology, 1988.)", "assessment": "Important note on scope: This is a diagnostic blood-flow monitoring study, not a therapeutic H₂ study. H₂ is used solely as an inert tracer gas via the clearance technique. The therapeutic intervention studied is endocrine (hormonal) treatment for prostate cancer. The paper provides no data on H₂ as an antioxidant, anti-inflammatory, or cancer therapy agent. Limitations: small n (19 patients); no control group; H₂ clearance is only the measurement tool; no H₂ therapy relevance.", "abstract": "Prostatic blood flow in 19 patients with prostatic adenocarcinoma was measured by the hydrogen gas clearance method before and during endocrine treatment. Prostatic volume was reduced to 70 per cent of the pre-treatment volume by 3 months after the beginning of treatment. Prostatic blood flow was remarkably depressed in patients who had never had any treatment of the prostatic carcinoma (22.2 +/- 8.3 ml. per minute per 100 gm.), while prostatic blood flow increased significantly after endocrine treatment (56.3 +/- 21.8 ml. per minute per 100 gm.). It was likely that prostatic blood flow increased as the prostate volume decreased. Final histology of serial prostatic biopsy specimens after endocrine treatment, revealed distinct deterioration of tumor cells and slight stromal hyperplasia compared to the initial pre-treatment biopsy. The stromal-epithelial ratio, which was calculated by computer-assisted image analysis, was markedly increased after endocrine treatment. Our study indicated that endocrine treatment caused a growth-inhibitory effect that was accompanied by increased blood flow in the prostatic carcinoma.", "conclusion": "The stromal-epithelial ratio, which was calculated by computer-assisted image analysis, was markedly increased after endocrine treatment. Our study indicated that endocrine treatment caused a growth-inhibitory effect that was accompanied by increased blood flow in the prostatic carcinoma." }, { "pmid": "3348155", "year": 1988, "title": "All yogurts are not created equal.", "title_en": null, "title_de": "Nicht alle Joghurts sind gleich", "journal": "The American journal of clinical nutrition", "authors": "Wytock et al.", "author_search": "wytock wytock", "doi": "10.1093/ajcn/47.3.454", "doi_url": "https://doi.org/10.1093/ajcn/47.3.454", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/3348155/", "url": "https://h2medicine.org/studies/study-wytock-1988-all-yogurts-not-created/", "methods": [], "indications": [ "other" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "breath-test", "headline": "1988 · Wytock et al. — All Yogurts Are Not Created Equal", "summary": "Not all yogurt brands are equally effective at helping lactose-intolerant people digest lactose — the key variable is the lactase activity of the bacterial cultures used. In eight lactose-malabsorbing subjects, breath hydrogen testing revealed that Dannon and Royal Maid yogurts significantly improved lactose absorption compared to plain lactose, while Borden yogurt did not. (The American Journal of Clinical Nutrition, 1988.)", "assessment": "Important note on scope: This is a gastrointestinal diagnostic study using breath H₂ as a measurement tool. H₂ is the biomarker for fermentation, not the therapeutic agent. The study provides useful gastroenterology and nutrition data on yogurt brands and lactose malabsorption. The null finding on symptom correlation is clinically important. No H₂ therapy relevance: this paper does not study H₂ administration as a health intervention. Limitations: very small n (8 subjects); only 3 yogurt brands tested; no randomisation or blinding described; single-centre design.", "abstract": "Because of autodigestion of lactose by its endogenous bacteria, the lactose in yogurt is better absorbed than other sources of lactose in lactase-deficient subjects. To investigate possible differences among brands of yogurt in this autodigesting capacity, we challenged eight lactose-malabsorbing subjects with 20 g oral lactose and three different brands of yogurt (Borden, Dannon, and Royal Maid). As a quantitative measure of carbohydrate absorption, end-alveolar breath samples were collected for 8 h and assayed for hydrogen gas. Symptoms were scored by questionnaire every 30 min for 8 h. The cumulative breath H2 and the area under the discontinuous curve of breath-H2 concentration decreased relative to lactose results after ingestion of Dannon and Royal Maid but not after Bordon yogurt. no correlation of symptoms with the degree of carbohydrate malabsorption was demonstrated. We conclude that the lactase activity of yogurt cultures varies among brands.", "conclusion": "no correlation of symptoms with the degree of carbohydrate malabsorption was demonstrated. We conclude that the lactase activity of yogurt cultures varies among brands." }, { "pmid": "2963569", "year": 1988, "title": "Endoscopic measurement of gastric mucosal blood flow by laser Doppler velocimetry: effect of chronic esophageal variceal sclerosis.", "title_en": null, "title_de": "Endoskopische Messung des Magenmukosa-Blutflusses mittels Laser-Doppler-Velocimetrie: Wirkung der chronischen Ösophagusvarizen-Sklerosierung", "journal": "The American surgeon", "authors": "Chung et al.", "author_search": "chung chung", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/2963569/", "url": "https://h2medicine.org/studies/study-chung-1988-endoscopic-measurement-gastric-mucosal/", "methods": [], "indications": [ "cardiovascular" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "tracer-clearance", "headline": "1988 · Chung et al. — Endoscopic Measurement of Gastric Mucosal Blood Flow by Laser Doppler Velocimetry: Effect of Chronic Esophageal Variceal Sclerosis", "summary": "A technique validation study demonstrating that laser Doppler velocimetry can measure gastric mucosal blood flow endoscopically — calibrated against hydrogen gas clearance as the reference standard. In portal-hypertensive patients, gastric mucosal blood flow was elevated, but sclerotherapy of oesophageal varices did not alter it. (The American Surgeon, 1988.)", "assessment": "Important note on scope: This is a gastroenterology methodology and diagnostic study. The hydrogen gas clearance technique is used only as a calibration reference — H₂ is the gold-standard comparator, not the therapeutic agent. The study involves both animal (dog) experiments for technical validation and human clinical measurements. The clinical null finding (sclerotherapy not changing mucosal flow) is relevant to gastroenterology practice but has no H₂ therapy implications. Limitations: mixed animal/human design; n for human clinical portion not specified in abstract; no therapeutic H₂ endpoint.", "abstract": "A technique of endoscopic measurement of gastric mucosal blood flow using laser Doppler velocimetry was described. The technique was validated in the laboratory by performing endoscopic measurement of gastric mucosal blood flow in the dog simultaneously with application of a second probe at open operation, utilizing the same laser Doppler flowmeter. Probe pressure causing minor dimpling (less than 20 gm/cm2) was found to cause insignificant alteration of mucosal blood flow. Criteria were developed to aid separation of artifacts introduced by probe motion. A conversion factor was established for converting the readout of the instrument (Hertz x 10(2] into ml/100g/min by synchronously measuring mucosal blood flow by hydrogen gas clearance technique and laser Doppler velocimetry in the gastric and duodenal mucosa. In patients with portal hypertension gastric mucosal blood flow was determined before and after sclerotherapy, and compared to the gastric mucosal blood flow in subjects without portal hypertension. Gastric mucosal blood flow was elevated in portal hypertensives, but sclerotherapy did not appear to cause changes in blood flow. Endoscopic mucosal blood flow measurement is non-invasive, practical and of potential value in clinical investigation of gastrointestinal pathophysiology.", "conclusion": "Gastric mucosal blood flow was elevated in portal hypertensives, but sclerotherapy did not appear to cause changes in blood flow. Endoscopic mucosal blood flow measurement is non-invasive, practical and of potential value in clinical investigation of gastrointestinal pathophysiology." }, { "pmid": "3653647", "year": 1987, "title": "Gastroduodenal mucosal hemodynamics by endoscopic reflectance spectrophotometry.", "title_en": null, "title_de": "Gastroduodenale Mukosa-Hämodynamik mittels endoskopischer Reflexionsspektrophotometrie", "journal": "Gastrointestinal endoscopy", "authors": "Leung et al.", "author_search": "leung leung", "doi": "10.1016/s0016-5107(87)71599-5", "doi_url": "https://doi.org/10.1016/s0016-5107(87)71599-5", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/3653647/", "url": "https://h2medicine.org/studies/study-leung-1987-gastroduodenal-mucosal-hemodynamics-endoscopic/", "methods": [], "indications": [ "liver", "cardiovascular" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "tracer-clearance", "headline": "1987 · Leung et al. — Gastroduodenal Mucosal Hemodynamics by Endoscopic Reflectance Spectrophotometry", "summary": "Endoscopic reflectance spectrophotometry — validated against hydrogen gas clearance as the reference standard — can non-invasively measure gastric and duodenal mucosal haemoglobin and oxygen saturation during routine endoscopy. The study found that portal hypertension does not significantly alter gastric mucosal blood flow, while active duodenal ulcers show increased blood flow at their margins. (Gastrointestinal Endoscopy, 1987.)", "assessment": "Important note on scope: This is a gastroenterology diagnostic methodology study. H₂ gas clearance is used purely as a calibration reference standard — it is not a therapeutic intervention. The study involves both animal experiments (dog) and human clinical endoscopy. Clinical findings on portal hypertension and duodenal ulcers are potentially relevant to gastroenterology but carry no H₂ therapy implications. Limitations: mixed animal/human design; sample sizes not specified for human cohort in abstract; H₂ used only as reference tool.", "abstract": "The reflectance spectrophotometric technique measures an index of mucosal hemoglobin concentration and an index of oxygen saturation by spectral analysis of light reflected from the mucosal surface. Using a commercially available unit, a technique for obtaining reproducible endoscopic measurements with acceptable intraobserver and interobserver variability was developed in the anesthetized dogs. The reflectance spectrophotometric finding that experimentally induced prehepatic portal hypertension did not affect gastric mucosal blood flow was confirmed by hydrogen gas clearance measurements. Endoscopic studies in patients with active duodenal ulcer disease revealed a higher index of mucosal hemoglobin concentration and a normal index of oxygen saturation (i.e., an increase in blood flow) at the margin of the ulcer compared with the adjacent normal appearing mucosa.", "conclusion": "The reflectance spectrophotometric finding that experimentally induced prehepatic portal hypertension did not affect gastric mucosal blood flow was confirmed by hydrogen gas clearance measurements. Endoscopic studies in patients with active duodenal ulcer disease revealed a higher index of mucosal hemoglobin concentration and a normal index of oxygen saturation (i.e., an increase in blood flow) at" }, { "pmid": "3303890", "year": 1987, "title": "Detection of intracardiac left-to-right shunting in adults: a prospective analysis of the variability of the standard indocyanine green technique in patients without shunting.", "title_en": null, "title_de": "Nachweis intrakardialer Links-Rechts-Shunts bei Erwachsenen: eine prospektive Analyse der Variabilität der Standard-Indocyaningrün-Technik", "journal": "The American journal of cardiology", "authors": "Niggemann et al.", "author_search": "niggemann niggemann", "doi": "10.1016/0002-9149(87)90242-6", "doi_url": "https://doi.org/10.1016/0002-9149(87)90242-6", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/3303890/", "url": "https://h2medicine.org/studies/study-niggemann-1987-detection-intracardiac-left-right/", "methods": [], "indications": [ "cardiovascular", "respiratory" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "tracer-clearance", "headline": "1987 · Niggemann et al. — Detection of Intracardiac Left-to-Right Shunting in Adults: A Prospective Analysis of the Variability of the Standard Indocyanine Green Technique", "summary": "In 66 adult patients confirmed shunt-free by the ultrasensitive hydrogen inhalation method, the indocyanine green dye technique showed percentage „shunts“ ranging from −9 % to +26 % — establishing for the first time the normal variability range for this diagnostic test. The practical implication: indocyanine green results below +26 % cannot reliably diagnose a true shunt. (The American Journal of Cardiology, 1987.)", "assessment": "Important note on scope: This is a cardiac diagnostic methodology study. H₂ inhalation is used as the gold-standard method to confirm absence of shunting — it is the reference comparator, not a therapeutic intervention. The study is methodologically clean and the clinical impact is meaningful (establishing the normal range for a widely used diagnostic test). No H₂ therapy relevance. Limitations: the n = 66 is adequate for establishing a normal range but limited to adult patients; single-centre prospective design; H₂ as reference tool only.", "abstract": "Intracardiac left-to-right shunting may be detected and quantitated by an oximetric analysis of blood from the right-sided cardiac chambers and prominent early recirculation of indocyanine green after it is injected into the central venous circulation and sampled from a systemic artery. Although the variability of oximetric measurements has been established in patients without shunting and a range of normal has been determined for the technique, the variability of the indocyanine green method among persons without shunting has not been clarified; as a result, a range of normal for indocyanine green has not been established. In 66 adult patients in whom hydrogen inhalation (an extremely sensitive technique for detecting even very small intracardiac left-to-right shunts) revealed no shunting, indocyanine green curves were generated by injection into the pulmonary artery as blood was sampled from a systemic artery. In these patients the percentage left-to-right shunt (that is, the percentage of pulmonary blood flow reaching the lungs through an intracardiac shunt) (determined with the equation of Carter et al) ranged from -9% to +26% (+7 +/- 8%, mean +/- standard deviation). There was no definable relation between the percentage left-to-right shunt and the indicator dilution measurement of cardiac output. Thus, these data establish a range of normal for the indocyanine green technique of detecting and measuring intracardiac left-to-right shunting. If this technique is to be used reliably to detect shunting, its results must demonstrate a percentage shunt in excess of +26%.", "conclusion": "Thus, these data establish a range of normal for the indocyanine green technique of detecting and measuring intracardiac left-to-right shunting. If this technique is to be used reliably to detect shunting, its results must demonstrate a percentage shunt in excess of +26%." }, { "pmid": "3578092", "year": 1987, "title": "Deuterium and oxygen-18 measurements on microliter samples of urine, plasma, saliva, and human milk.", "title_en": null, "title_de": "Deuterium- und Sauerstoff-18-Messungen an Mikroliterproben von Urin, Plasma, Speichel und Muttermilch.", "journal": "The American journal of clinical nutrition", "authors": "Wong et al.", "author_search": "wong wong", "doi": "10.1093/ajcn/45.5.905", "doi_url": "https://doi.org/10.1093/ajcn/45.5.905", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/3578092/", "url": "https://h2medicine.org/studies/study-wong-1987-deuterium-oxygen-measurements-microliter/", "methods": [ "inhalation" ], "indications": [ "metabolic" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "1987 · Wong — Deuterium and oxygen-18 measurements on microliter samples of urine, plasma, saliva, and human milk.", "summary": "Improved laboratory methods for measuring stable isotope ratios (deuterium/²H and ¹⁸O) in tiny biological fluid samples — down to 10 microliters — were developed and validated, enabling more precise studies of body composition and energy expenditure in humans. Hydrogen gas generation from microliter samples is a key preparatory step in this isotope measurement methodology. (The American Journal of Clinical Nutrition, 1987.)", "assessment": "This is a methodological in-vitro study developing isotope ratio measurement techniques for nutritional research. Hydrogen gas generation is a sample preparation step, not a therapeutic application. There is no relevance to molecular hydrogen therapy. The paper is primarily of interest to researchers using doubly-labelled water methods for body composition or metabolic studies.", "abstract": "Improved methods to measure 2H:1H and 18O:16O isotope ratios on microliter samples of biological fluids are described. Enriched levels of 2H (580%) and 18O (256%) in urine, plasma, saliva, and human milk can be measured with a precision of 3.2% (n = 200) and 0.97% (n = 200) and an accuracy of -4.6 +/- 4.4% (mean +/- SD, n = 200) and -0.32 +/- 0.87% (mean +/- SD, n = 200), respectively. Hydrogen gas samples are generated from 10 microL of undistilled fluid by zinc reduction in quartz reaction vessels. Water-CO2 equilibration of a 100-microL sample for 18O measurement is completed in 10 h using a modified commercial equilibration system. These methodological improvements facilitate and extend the use of 2H and 18O tracers in studies of body composition and energy expenditure.", "conclusion": "Water-CO2 equilibration of a 100-microL sample for 18O measurement is completed in 10 h using a modified commercial equilibration system. These methodological improvements facilitate and extend the use of 2H and 18O tracers in studies of body composition and energy expenditure." }, { "pmid": "3095080", "year": 1986, "title": "Comparison of oral lavage methods for preoperative colonic cleansing.", "title_en": null, "title_de": "Vergleich oraler Lavage-Methoden zur präoperativen Darmreinigung", "journal": "Diseases of the colon and rectum", "authors": "Beck et al.", "author_search": "beck beck", "doi": "10.1007/bf02555311", "doi_url": "https://doi.org/10.1007/bf02555311", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/3095080/", "url": "https://h2medicine.org/studies/study-beck-1986-comparison-oral-lavage-methods/", "methods": [], "indications": [ "other" ], "evidence_level": 3, "human": true, "therapeutic": false, "h2category": "byproduct", "headline": "1986 · Beck et al. — Comparison of Oral Lavage Methods for Preoperative Colonic Cleansing", "summary": "A randomised comparison of two bowel preparation methods before colon surgery found that polyethylene glycol electrolyte lavage outperforms 10 % mannitol solution in cleansing quality, patient tolerance, and — critically — safety: mannitol produces combustible hydrogen gas levels in the colon, posing an electrosurgery fire risk. (Diseases of the Colon and Rectum, 1986.)", "assessment": "This is a randomised clinical trial of surgical bowel preparation methods, not an H₂ therapy study. Hydrogen gas appears as a safety hazard (colonic fermentation product of mannitol) and as a measured surgical risk variable. The finding is clinically important for surgical practice. For the H₂ therapy database, this paper provides indirect context: it confirms endogenous colonic H₂ production at potentially significant concentrations from fermentable carbohydrates — consistent with the gut-H₂ hypothesis. Limitations: n = 80 (large enough for the primary endpoint); primary outcomes are cleansing quality and patient tolerance, not H₂ physiology; the H₂ measurement is a secondary safety check, not the primary study aim.", "abstract": "Polyethylene glycol electrolyte lavage solution was compared with a 10 percent mannitol solution for preoperative colonic cleansing. Eighty patients were prepared randomly with one of these solutions on the afternoon prior to surgery. Colonic cleansing was better with polyethylene glycol electrolyte lavage (90 percent optimal cleansing vs. 75 percent). Analysis of hematologic, biochemical, and weight changes before and after the bowel preparation, demonstrated a mild subclinical dehydration with the use of mannitol. Evaluation of patient tolerance demonstrated more nausea, cramps, and abdominal pain with mannitol. Other symptoms were similar with both preparations. Colonic hydrogen gas was sampled during surgery, and two patients in the mannitol group had combustible levels. This study confirms that both 10 percent mannitol and polyethylene glycol electrolyte lavage are safe, effective methods of preoperative bowel cleansing. Better cleansing, patient tolerance, and lower hydrogen gas level make polyethylene glycol electrolyte lavage the preferred method.", "conclusion": "This study confirms that both 10 percent mannitol and polyethylene glycol electrolyte lavage are safe, effective methods of preoperative bowel cleansing. Better cleansing, patient tolerance, and lower hydrogen gas level make polyethylene glycol electrolyte lavage the preferred method." }, { "pmid": "3749634", "year": 1986, "title": "[Measurement of skin blood flow using inhaled hydrogen gas clearance method].", "title_en": null, "title_de": "Messung des Haut-Blutflusses mittels inhalierter Wasserstoffgas-Clearance-Methode", "journal": "Kokyu to junkan. Respiration & circulation", "authors": "Nohara et al.", "author_search": "nohara nohara", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/3749634/", "url": "https://h2medicine.org/studies/study-nohara-1986-measurement-skin-blood-flow/", "methods": [], "indications": [ "skin-aging" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "tracer-clearance", "headline": "1986 · Nohara et al. — Measurement of Skin Blood Flow Using Inhaled Hydrogen Gas Clearance Method", "summary": "This study from 1986 used inhaled hydrogen gas as a diagnostic tracer to measure skin blood flow — not as a therapeutic agent. The hydrogen gas clearance method tracks how quickly inhaled H₂ is washed out of tissue, which reflects local perfusion. This is a methodological paper, not a therapeutic H₂ study. (Kokyu to Junkan, 1986.)", "assessment": "Important caveat: this is not a therapeutic H₂ study. Hydrogen gas is used here as an inert diagnostic tracer to quantify skin blood flow — the same principle as a dye-dilution measurement. No therapeutic H₂ dose is administered, and no health outcome is studied. The abstract is unavailable (no DOI, Japanese-language journal from 1986). Limitations: no abstract retrievable; methodology paper only; not applicable to H₂ therapeutic efficacy; very old study (1986) with no modern replication context.", "abstract": null, "conclusion": null }, { "pmid": "3943456", "year": 1986, "title": "Hemodynamics of the gastric mucosa and gastric ulceration in rats and in patients with gastric ulcer.", "title_en": null, "title_de": "Hämodynamik der Magenmukosa und Magenulzeration bei Ratten und bei Patienten mit Magenulkus.", "journal": "Digestive diseases and sciences", "authors": "Sato et al.", "author_search": "sato sato", "doi": "10.1007/bf01309321", "doi_url": "https://doi.org/10.1007/bf01309321", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/3943456/", "url": "https://h2medicine.org/studies/study-sato-1986-hemodynamics-gastric-mucosa-gastric/", "methods": [ "inhalation" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "1986 · Sato — Hemodynamics of the gastric mucosa and gastric ulceration in rats and in patients with gastric ulcer.", "summary": "A spectrophotometric method for non-invasive assessment of gastric mucosal oxygen supply was validated against hydrogen gas clearance and other blood flow techniques, and applied to study how microcirculation affects ulcer formation in rat stress models and ulcer healing in human patients. This animal and clinical observation study uses H₂ clearance purely as a reference measurement method, not as a therapeutic agent. (Digestive Diseases and Sciences, 1986.)", "assessment": "This is an animal and clinical observational study using H₂ gas clearance as one of several validated reference methods for blood flow measurement. No therapeutic H₂ is involved. The paper contributes to understanding gastric mucosal blood flow in ulcer pathophysiology but has no bearing on molecular hydrogen therapy. Note: this is an animal study (rats) plus human observational data — results cannot be directly extrapolated to human therapeutic interventions.", "abstract": "The microcirculation is the fundamental nutrient supply and waste removal system of all tissues. Recent improvements in spectrophotometric technique have made possible the noninvasive assessment of oxygen supply and utilization in the gastric mucosa. The authors have utilized such methods to assess gastric mucosal hemodynamics. The technique permitted further clarification of the roles of the gastric microcirculation, mucosal oxygenation, and acid secretion in the pathogenesis of stress ulcers in the stomach of rats. Furthermore, it provided important information on the function of gastric mucosal hemodynamics in the healing of gastric ulcers in man. The technique is described along with the authors' correlation studies between spectrophotometric data and other techniques for measuring gastric blood flow (hydrogen gas clearance and aminopyrine clearance methods and direct electromagnetic flowmeter techniques) and the prevention of ulcerogenesis.", "conclusion": "Furthermore, it provided important information on the function of gastric mucosal hemodynamics in the healing of gastric ulcers in man. The technique is described along with the authors' correlation studies between spectrophotometric data and other techniques for measuring gastric blood flow (hydrogen gas clearance and aminopyrine clearance methods and direct electromagnetic flowmeter techniques) " }, { "pmid": "3485763", "year": 1986, "title": "[Etiopathogenesis of hemorrhagic gastritis after esophageal transection extended devascularization in variceal patients].", "title_en": null, "title_de": "Ätiopathogenese der hämorrhagischen Gastritis nach Ösophagustransektion mit erweiterter Devaskularisation bei Varizenpatienten", "journal": "Nihon Geka Gakkai zasshi", "authors": "Satani", "author_search": "satani satani", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/3485763/", "url": "https://h2medicine.org/studies/study-satani-1986-etiopathogenesis-hemorrhagic-gastritis-after/", "methods": [], "indications": [ "cardiovascular" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "tracer-clearance", "headline": "1986 · Satani — Etiopathogenesis of Hemorrhagic Gastritis after Esophageal Transection and Extended Devascularization in Variceal Patients", "summary": "This surgical study from 1986 investigated why some cirrhotic patients develop hemorrhagic gastritis after esophageal variceal surgery — using hydrogen gas clearance as a tool to measure gastric blood flow, not as a therapy. The findings point to progressive gastric tissue hypoxia despite maintained blood flow as the key mechanism. (Nihon Geka Gakkai Zasshi, 1986.)", "assessment": "Important caveat: H₂ is used here as a diagnostic tracer only, not as a therapeutic agent. The hydrogen gas clearance method is employed to measure gastric mucosal perfusion — this is standard clinical physiology methodology from the 1980s, entirely unrelated to H₂ medicine. The „drinking-hrw“ categorization in the source database appears erroneous. Limitations: very small sample (n = 10); no control group; historical study (1986) without modern imaging or endoscopic correlation; the hydrogen inhalation serves only a measurement purpose. Clinically interesting for its physiology of post-surgical hypoxia, but not evidence for H₂ therapy.", "abstract": "Postoperative hemorrhagic gastritis is often observed in cirrhotic patients with esophageal varices. We studied gastric and systemic hemodynamics including oxygen demand and supply before and after surgery to demonstrate the etiology of this entity. Ten cirrhotic patients with esophageal varices were examined in this study. In hemodynamic studies, gastric blood flow and tissue oxygen tension (PtO2) of cardia portion were measured by hydrogen gas clearance method and PtO2 sensor. And systemic hemodynamics were measured by Swan-Ganz catheter including O2 availability, O2 extraction rate, O2 consumption, A-VCDO2, and shunt rate. Moreover blood temperature, pH, Hb, P50, and 2,3-DPG, and oxygenic dissociation curve, were also monitored. Gastric blood flow showed moderate reduction immediately after surgery and returned to the previous value by the 7th postoperative day. But the value of PtO2 dropped gradually for 7 days after surgery. Marked systemic hyperdynamic circuration was observed before surgery and it was accelerated after surgery. In oxygen demand and supply, moderate to marked reduction was seen postoperatively. Oxygen dissociation curve was shifted to the left after surgery due to significant decrease in P50 and 2,3-DPG. These results suggest extended devascularization causes severe damage of system oxygenic demand and supply, and progressive gastric tissue hypoxia without reduction of blood flows may result in hemorrhagic gastritis.", "conclusion": "Oxygen dissociation curve was shifted to the left after surgery due to significant decrease in P50 and 2,3-DPG. These results suggest extended devascularization causes severe damage of system oxygenic demand and supply, and progressive gastric tissue hypoxia without reduction of blood flows may result in hemorrhagic gastritis." }, { "pmid": "2990189", "year": 1985, "title": "Dietary fiber effects on passage rate and breath hydrogen.", "title_en": null, "title_de": "Auswirkungen von Ballaststoffen auf die Passagerate und den Atemwasserstoff", "journal": "The American journal of clinical nutrition", "authors": "Hanson et al.", "author_search": "hanson hanson", "doi": "10.1093/ajcn/42.1.44", "doi_url": "https://doi.org/10.1093/ajcn/42.1.44", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/2990189/", "url": "https://h2medicine.org/studies/study-hanson-1985-dietary-fiber-passage-rate/", "methods": [], "indications": [ "other" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "breath-test", "headline": "1985 · Hanson et al. — Dietary Fiber Effects on Passage Rate and Breath Hydrogen", "summary": "This 1985 study measured how different types of dietary fiber affect intestinal transit and the amount of hydrogen gas produced by gut bacteria and measurable in exhaled breath. Gel-like fibers (oat bran, citrus flour) produced more breath H₂ and less accelerated transit than particulate fibers (wheat bran, corn bran). This is a nutrition/gastroenterology study using breath H₂ as a diagnostic marker, not as a therapy. (American Journal of Clinical Nutrition, 1985.)", "assessment": "This is a nutritional gastroenterology study, not a therapeutic H₂ study. Breath H₂ is used exclusively as a diagnostic marker of colonic fermentation and transit — it is the outcome measured, not an intervention. No H₂ is administered. Limitations: extremely small sample (n = 5); no randomization described; single-day meal challenge; 1985 methodology predates modern breath H₂ standardization; no clinical endpoints (symptoms, inflammation, etc.) assessed. Provides useful context for understanding endogenous H₂ production from the gut, but contributes no evidence for H₂ as a therapeutic agent.", "abstract": "Fermentation of fiber and passage to the large intestine were monitored by measuring hydrogen gas (H2) concentration in expired breath. Five subjects consumed meals containing no added fiber or 40 g of wheat bran (WB), corn bran (CB), oat bran (OB), or citrus flour (CF) replacing white flour. Breath samples were obtained at 30 min intervals for 9 h after the test meals. Mean H2 concentration (ppm), averaged over the 9 h test period, ranged from 7.5 (CB) to 12.0 (OB) and tended to increase with addition of OB, CF, or WB but decrease with addition of CB. Hours from the meal to the highest H2 peaks were 4.7 (WB), 5.6 (CB), 6.2 (OB), 6.4 (CF), and 8.2 (basal). The gel-like fibers (OB and CF) resulted in greater H2 concentration and less acceleration of passage rate than the particulate fibers (WB and CB).", "conclusion": "Hours from the meal to the highest H2 peaks were 4.7 (WB), 5.6 (CB), 6.2 (OB), 6.4 (CF), and 8.2 (basal). The gel-like fibers (OB and CF) resulted in greater H2 concentration and less acceleration of passage rate than the particulate fibers (WB and CB)." }, { "pmid": "3989351", "year": 1985, "title": "Intestinal metabolism of a random-bonded polyglucose bulking agent in humans: in vitro and in vivo studies of hydrogen evolution.", "title_en": null, "title_de": "Intestinaler Stoffwechsel eines zufallsverknüpften Polyglucose-Füllstoffs beim Menschen: In-vitro- und In-vivo-Studien zur Wasserstoffentwicklung", "journal": "The Journal of laboratory and clinical medicine", "authors": "Solomons et al.", "author_search": "solomons solomons", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/3989351/", "url": "https://h2medicine.org/studies/study-solomons-1985-intestinal-metabolism-random-bonded/", "methods": [], "indications": [ "fundamentals-safety" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "breath-test", "headline": "1985 · Solomons et al. — Intestinal Metabolism of a Random-Bonded Polyglucose Bulking Agent in Humans: In Vitro and In Vivo Studies of Hydrogen Evolution", "summary": "This 1985 study investigated how much polydextrose — a proposed low-calorie bulking agent — is fermented by gut bacteria, using breath H₂ as the marker of fermentation. Polydextrose alone produced minimal breath H₂ (comparable to glucose), but when mixed with milk it significantly increased fermentation. This is a food safety/nutrition study, not a therapeutic H₂ investigation. (Journal of Laboratory and Clinical Medicine, 1985.)", "assessment": "This is a dietary safety and gut physiology study, not a therapeutic H₂ intervention. Breath H₂ is used solely as a non-invasive marker of colonic fermentation — the tool of measurement, not the therapy. No H₂ is administered, and no health outcomes are studied. Limitations: small sample (n not precisely stated); only breath H₂ measured (no symptoms, no mucosal assessment); the in vitro fecal incubation data complement but do not replace in vivo findings; food matrix interactions are complex and not fully explained mechanistically. Not applicable to H₂ medicine.", "abstract": "In vivo and in vitro experiments were conducted to determine the extent of intestinal fermentation of polydextrose, a random-bonded glucose polymer proposed as a low-calorie bulking agent in weight-reducing diets. The evolution of hydrogen gas was the index of bacterial fermentation. Oral ingestion of 15 gm polydextrose by healthy volunteers produced a flat breath hydrogen response, equivalent to that of glucose, and significantly less than that of lactulose. In vitro incubation of a polydextrose solution with fecal homogenates produced 24.8% of the hydrogen production of a comparable glucose solution. When either milk or lactose-hydrolyzed milk containing 18 gm intrinsic carbohydrate was mixed with 18 gm polydextrose, a significantly greater breath hydrogen excretion was observed as compared with the respective beverages alone. There is minimal in vivo fermentation of polydextrose when consumed alone, but when mixed into foods it may produce carbohydrate malabsorption or itself be more readily fermented.", "conclusion": "When either milk or lactose-hydrolyzed milk containing 18 gm intrinsic carbohydrate was mixed with 18 gm polydextrose, a significantly greater breath hydrogen excretion was observed as compared with the respective beverages alone. There is minimal in vivo fermentation of polydextrose when consumed alone, but when mixed into foods it may produce carbohydrate malabsorption or itself be more readily " }, { "pmid": "2578223", "year": 1985, "title": "Development of carbohydrate absorption in the fetus and neonate.", "title_en": null, "title_de": "Entwicklung der Kohlenhydratabsorption beim Fetus und Neugeborenen", "journal": "Pediatrics", "authors": "Mobassaleh et al.", "author_search": "mobassaleh mobassaleh", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/2578223/", "url": "https://h2medicine.org/studies/study-mobassaleh-1985-development-carbohydrate-absorption-fetus/", "methods": [], "indications": [ "sports-exercise", "pregnancy" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "breath-test", "headline": "1985 · Mobassaleh et al. — Development of Carbohydrate Absorption in the Fetus and Neonate", "summary": "This 1985 review describes how carbohydrate digestion enzymes and absorption mechanisms mature during fetal development and the neonatal period — and how breath hydrogen testing can non-invasively assess carbohydrate absorption status in young infants. Hydrogen here is a diagnostic marker produced by gut bacteria from unabsorbed carbohydrates, not a therapeutic agent. (Pediatrics, 1985.)", "assessment": "This is a developmental pediatrics review — not a therapeutic H₂ study. H₂ appears in the context of gut fermentation physiology and breath testing methodology; it is neither administered nor studied as a therapeutic agent. The database fields „methods: inhalation, drinking-hrw“ appear to be erroneous indexing for this article. Limitations: this is a narrative review from 1985; no primary data, no control groups, no effect sizes; some enzyme maturation data may have been updated by subsequent research. Relevant for understanding endogenous H₂ biology, but provides no evidence for therapeutic H₂ use.", "abstract": "Maturation of mechanisms for carbohydrate absorption occurs in a defined sequence during human fetal development. The intestinal enzymes, lactase, sucrase, maltase, isomaltase, and glucoamylase, are at mature levels in the term fetus. Mature levels of pancreatic amylase activity and glucose transport occur postnatally, and levels are low in both the term and preterm neonate. In the preterm infant, sucrase, maltase, and isomaltase are usually fully active, but lactase activity, which increases markedly from 24 to 40 weeks, may be low depending upon fetal age. Despite these developmental patterns, clinical lactose intolerance is uncommon. Postnatal adaptive responses to ingested carbohydrates lead to competent carbohydrate absorption. Inadequately absorbed carbohydrates are salvaged by colonic flora through fermentation of carbohydrates to hydrogen gas and short-chain fatty acids; the latter are readily absorbed by the colon. In this setting, carbohydrate tends to be absent from the stool. Noninvasive reflection of the status of carbohydrate absorption may be obtained from breath hydrogen testing, a technique of particular value in young infants.", "conclusion": "In this setting, carbohydrate tends to be absent from the stool. Noninvasive reflection of the status of carbohydrate absorption may be obtained from breath hydrogen testing, a technique of particular value in young infants." }, { "pmid": "6530800", "year": 1984, "title": "[Endoscopic measurement of gastric mucosal blood flow by hydrogen gas generated by electrolysis--comparison with H2-inhalation method].", "title_en": null, "title_de": "Endoskopische Messung des Magenmukosa-Blutflusses mittels durch Elektrolyse erzeugtem Wasserstoffgas – Vergleich mit der H₂-Inhalationsmethode", "journal": "Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology", "authors": "Nishiwaki et al.", "author_search": "nishiwaki nishiwaki", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/6530800/", "url": "https://h2medicine.org/studies/study-nishiwaki-1984-endoscopic-measurement-gastric-mucosal/", "methods": [], "indications": [ "other" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "tracer-clearance", "headline": "1984 · Nishiwaki et al. — Endoscopic Measurement of Gastric Mucosal Blood Flow by Hydrogen Gas Generated by Electrolysis — Comparison with H₂ Inhalation Method", "summary": "This 1984 study compared two methods for measuring gastric mucosal blood flow during endoscopy: generating H₂ locally via electrolysis versus the conventional inhaled H₂ gas clearance method. This is a diagnostic methodology paper — H₂ serves as a physiological tracer, not a therapeutic agent. (Nihon Shokakibyo Gakkai Zasshi, 1984.)", "assessment": "This is a diagnostic methodology comparison, not a therapeutic H₂ study. Both methods use H₂ as a non-therapeutic tracer to quantify blood flow. The abstract is unavailable (no DOI, Japanese-language journal from 1984). The database categorization includes „inhalation“ which accurately reflects the measurement method used — but this is diagnostic, not therapeutic inhalation. Limitations: no abstract available; historical study (1984); Japanese-language publication; methodology paper only.", "abstract": null, "conclusion": null }, { "pmid": "6745722", "year": 1984, "title": "Is raised breath hydrogen related to the pathogenesis of pneumatosis coli?", "title_en": null, "title_de": "Steht erhöhter Atemwasserstoff im Zusammenhang mit der Pathogenese der Pneumatosis coli?", "journal": "Gut", "authors": "Read et al.", "author_search": "read read", "doi": "10.1136/gut.25.8.839", "doi_url": "https://doi.org/10.1136/gut.25.8.839", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/6745722/", "url": "https://h2medicine.org/studies/study-read-1984-raised-breath-related-pathogenesis/", "methods": [], "indications": [ "sports-exercise" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "breath-test", "headline": "1984 · Read et al. — Is Raised Breath Hydrogen Related to the Pathogenesis of Pneumatosis Coli?", "summary": "This 1984 study investigated five patients with pneumatosis coli — a rare condition where gas-filled cysts form in the colon wall — finding that all had abnormally high fasting breath hydrogen, and that the cysts themselves contained 2–8% hydrogen gas. The data point toward bacterial overgrowth and anaerobic infection as contributors to cyst formation, rather than a simple mechanical gas accumulation. This is a pathophysiology investigation, not a therapeutic H₂ study. (Gut, 1984.)", "assessment": "This is a pathophysiology investigation of a rare gastrointestinal condition — not a therapeutic H₂ study. Breath H₂ and cyst gas composition are outcomes measured to understand disease mechanism. No H₂ is administered. The study's strength is its multi-method approach in a highly unusual patient group. Limitations: extremely small n (5 patients); no control group for most measurements; mechanistic hypotheses not definitively proven (competing explanations for H₂ source remain); the 14C glycocholate tests being normal is unexpected and not fully explained. Interesting for understanding H₂ biology in the gut, but provides no evidence for therapeutic H₂ use.", "abstract": "Clinical and physiological studies were carried out in five patients with pneumatosis coli in order to investigate the origin of the high fasting breath hydrogen concentration in this condition and to determine its possible significance in the pathogenesis of the disease. All five patients excreted abnormally high fasting concentrations of hydrogen in their breath (69 +/- 9 ppm, mean +/- SEM). Moreover, analysis of the contents of the gas filled cysts revealed between 2% and 8% of hydrogen gas. Colonic washout significantly reduced breath hydrogen concentrations to 9 +/- 6 ppm, but did not abolish the cysts. Conversely, deflation of the cysts was achieved with oxygen or antibiotics, though this only reduced breath hydrogen concentrations to about 66% of their original value. After feeding a radiolabelled meal, breath hydrogen concentrations rose before the meal appeared to reach the colon, suggesting overgrowth of anaerobic bacteria in the small intestine. Despite this, 14C glycocholate breath tests were within normal limits. An alternative possibility is that the high levels of hydrogen excreted in the breath may be produced in the intestinal lumen possibly from the fermentation of copious amounts of colonic mucus. Finally, measurement of whole gut transit time and stool weight suggested that patients were constipated despite passing mucus and blood. The relevance of our observations to the pathogenesis of submucosal cysts is unclear, but the data favour the hypothesis that these are produced by invasion of the colonic submucosa with anaerobic bacteria.", "conclusion": "Finally, measurement of whole gut transit time and stool weight suggested that patients were constipated despite passing mucus and blood. The relevance of our observations to the pathogenesis of submucosal cysts is unclear, but the data favour the hypothesis that these are produced by invasion of the colonic submucosa with anaerobic bacteria." }, { "pmid": "6745599", "year": 1984, "title": "Endoscopical determination of gastric mucosal blood flow by the crossed thermocouple method.", "title_en": null, "title_de": "Endoskopische Bestimmung des Magenmukosa-Blutflusses mittels der gekreuzten Thermoelement-Methode", "journal": "Gastroenterologia Japonica", "authors": "Hiramatsu et al.", "author_search": "hiramatsu hiramatsu", "doi": "10.1007/bf02779172", "doi_url": "https://doi.org/10.1007/bf02779172", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/6745599/", "url": "https://h2medicine.org/studies/study-hiramatsu-1984-endoscopical-determination-gastric-mucosal/", "methods": [], "indications": [ "other" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "breath-test", "headline": "1984 · Hiramatsu et al. — Endoscopical Determination of Gastric Mucosal Blood Flow by the Crossed Thermocouple Method", "summary": "This 1984 study introduced the crossed thermocouple method as an endoscopic alternative to the hydrogen gas clearance method for measuring gastric mucosal blood flow. The authors explicitly note that the H₂ inhalation required by the conventional method is „possibly harmful to humans“ — and their thermocouple method avoids it. This is a diagnostic methodology paper; H₂ is the technique being replaced, not a therapeutic agent. (Gastroenterologia Japonica, 1984.)", "assessment": "This is a diagnostic methodology development study, not a therapeutic H₂ investigation. The H₂ inhalation referenced is a comparative method being supplanted — it is not studied as therapy. Interestingly, the authors flagged H₂ inhalation as „possibly harmful to humans“ — a concern not supported by modern safety literature, but historically instructive. Limitations: small sample (n = 11 healthy controls); only one measurement session per subject; no clinical outcomes beyond the technical comparison; the phrasing „possibly harmful“ regarding H₂ inhalation appears unsubstantiated and reflects 1984 concerns rather than established toxicology.", "abstract": "A crossed thermocouple method in combination with endoscopy was applied to determine the blood flow rate of the human gastric mucosa. Determination was carried out with 11 healthy control subjects at 8 sites of the stomach. The blood flow rates at all sites in the corpus were found to be higher than those at the antrum. In subjects less than 50 years old the blood flow rate in the corpus was higher than in older subjects. These results were in agreed well with those obtained by the hydrogen gas clearance method, which is widely adopted clinically. The crossed thermocouple method is easily applicable to all sites in the gastric mucosa and the time required for the assay is very short. This method dose not require the inhalation of hydrogen gas which is necessary for the hydrogen gas clearance method and which is possibly harmful to humans. Although the values obtained by the crossed thermocouple method are relative to the value at a certain fixed site, this method will holds great potential for the determination of gastric mucosal blood flow rate.", "conclusion": "This method dose not require the inhalation of hydrogen gas which is necessary for the hydrogen gas clearance method and which is possibly harmful to humans. Although the values obtained by the crossed thermocouple method are relative to the value at a certain fixed site, this method will holds great potential for the determination of gastric mucosal blood flow rate." }, { "pmid": "6717636", "year": 1984, "title": "[The determination of hydrogen gas in the expired air for the diagnosis of carbohydrate resorption disorders].", "title_en": null, "title_de": "Die Bestimmung von Wasserstoffgas in der Ausatemluft zur Diagnose von Kohlenhydratresorptionsstörungen", "journal": "Nederlands tijdschrift voor geneeskunde", "authors": "Dolmans et al.", "author_search": "dolmans dolmans", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/6717636/", "url": "https://h2medicine.org/studies/study-dolmans-1984-determination-expired-air-diagnosis/", "methods": [], "indications": [ "other" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "breath-test", "headline": "1984 · Dolmans et al. — The Determination of Hydrogen Gas in Expired Air for the Diagnosis of Carbohydrate Resorption Disorders", "summary": "This 1984 Dutch review article describes breath hydrogen testing as a diagnostic tool for identifying carbohydrate malabsorption disorders — the same principle underlying lactose and fructose intolerance tests used today. Hydrogen is entirely a diagnostic marker here; no H₂ is administered therapeutically. (Nederlands Tijdschrift voor Geneeskunde, 1984.)", "assessment": "This is a clinical gastroenterology diagnostic methodology review — not a therapeutic H₂ study. Breath H₂ testing is described as a tool to diagnose carbohydrate absorption disorders; no H₂ is given as treatment. The abstract is not available (no DOI, Dutch-language journal from 1984). Limitations: no abstract available; historical review (1984); methodology review only; no primary data. Not applicable to H₂ therapeutic efficacy.", "abstract": null, "conclusion": null }, { "pmid": "6749107", "year": 1984, "title": "[Experimental and clinical studies on esophago-gastric hemodynamics before and after devascularization for esophageal varices].", "title_en": null, "title_de": "Experimentelle und klinische Studien zur ösophago-gastralen Hämodynamik vor und nach Devaskularisation bei Ösophagusvarizen", "journal": "Nihon Geka Gakkai zasshi", "authors": "Toyama", "author_search": "toyama toyama", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/6749107/", "url": "https://h2medicine.org/studies/study-toyama-1984-experimental-esophago-gastric-hemodynamics/", "methods": [], "indications": [ "liver", "cardiovascular" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "tracer-clearance", "headline": "1984 · Toyama — Experimental and Clinical Studies on Esophago-Gastric Hemodynamics Before and After Devascularization for Esophageal Varices", "summary": "This 1984 surgical study examined how esophago-gastric mucosal blood flow and tissue oxygen tension change after devascularization surgery for esophageal varices — using hydrogen gas clearance as a measurement tool in both dogs and humans. The key finding: the impact of extended devascularization on blood flow is smaller in cirrhotic patients than in normal animals, suggesting collateral circulation offers some protection. H₂ here is purely a diagnostic tracer. (Nihon Geka Gakkai Zasshi, 1984.)", "assessment": "Important caveat: H₂ is used here exclusively as a diagnostic tracer (clearance method), not as a therapeutic agent. This is a surgical physiology study combining animal and human data. The animal part (26 normal dogs + 8 portal hypertensive dogs) is not a human study — the human component comprises 10 cirrhotic patients. Limitations: small human sample (n = 10); mixed animal/human design; no long-term human follow-up; the animal model differences may not fully translate to human physiology. Not evidence for H₂ therapy.", "abstract": "Esophago-gastric hemodynamics subsequent to devascularization was studied in a view of changes in mucosal blood flow and tissue oxygen tension (PtO2). Thirty-four mongrel dogs (26 normal dogs and 8 portal hypertensive dogs) were used in experimental studies, and mucosal blood flow was determined by means of hydrogen gas clearance. Remarkable reduction of a 73% in gastric cardia was recognized on normal dogs just after extended devascularization, and those dogs died of severe gastric necrosis within 4 days after surgery. Reduction of a 28.5% in the cardia was found by the devascularization on portal hypertensive dogs produced by a whole liver compression. These portal hypertensive dogs survived for 2 weeks after surgery, and then mucosal blood flows were returned to the previous levels. Liver cirrhosis (10 cases) with esophageal varices were used for clinical studies. Gastric hemodynamics was measured by PtO2 before and after devascularization. Reduction of a 25.7% in the cardia was recognized on cirrhotic patients. These results suggest that influences of extended devascularization on esophago-gastric hemodynamics would be a small in cirrhotic patients with esophageal varices.", "conclusion": "Reduction of a 25.7% in the cardia was recognized on cirrhotic patients. These results suggest that influences of extended devascularization on esophago-gastric hemodynamics would be a small in cirrhotic patients with esophageal varices." }, { "pmid": "6715939", "year": 1984, "title": "[The cervical blood flow using hydrogen gas clearance method].", "title_en": null, "title_de": "Der zervikale Blutfluss mittels Wasserstoffgas-Clearance-Methode", "journal": "Nihon Sanka Fujinka Gakkai zasshi", "authors": "Sakiyama", "author_search": "sakiyama sakiyama", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/6715939/", "url": "https://h2medicine.org/studies/study-sakiyama-1984-cervical-blood-flow-clearance/", "methods": [], "indications": [ "sports-exercise", "pregnancy" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "tracer-clearance", "headline": "1984 · Sakiyama — The Cervical Blood Flow Using Hydrogen Gas Clearance Method", "summary": "This 1984 Japanese study measured cervical blood flow across the menstrual cycle and various stages of pregnancy using inhaled hydrogen gas clearance — a diagnostic technique, not a therapy. Cervical blood flow was highest in early pregnancy (6–7 weeks) and declined significantly toward term, possibly reflecting cervical ripening. (Nihon Sanka Fujinka Gakkai Zasshi, 1984.)", "assessment": "This is a gynecological physiology measurement study — not a therapeutic H₂ investigation. Hydrogen gas clearance is used purely as a diagnostic technique to quantify tissue blood flow. No therapeutic H₂ is administered. Limitations: small sample sizes (exact n per subgroup not always stated: 19 non-pregnant; 6–7 early pregnancy cases; single-site measurements); historical study (1984) with no modern imaging comparison; no clinical outcomes beyond the hemodynamic measurements; the physiological significance of the molar pregnancy finding is not explored in depth. Not applicable to H₂ medicine.", "abstract": "Employing a hydrogen gas clearance method, cervical blood flow abbre . CxBF hereafter, was measured in non-pregnant and various pregnant stages and the following results were obtained. CxBF in 19 non-pregnant cases was 54.1 +/- 22.0 ml/min/100 gr. The measurement was 63.1 +/- 38 in the early, 54.5 in the late proliferative, 65.2 +/- 17.1 in the early and 25.3 +/- 8.9 in the late secretory stage, suggesting that the measurement of CxBF was effected by hormonal conditions. No relationship was found between uterine weight and CxBF . CxBF was 96.8 +/- 11.3 in 6-7, 48.6 +/- 26.4 in 8, 55.5 +/- 9.8 in 9-13 gestational weeks, that is it was highest in the early stages and gradually decreased with the advance of pregnancy. CxBF was considered to be affected by the physical distance between the cervix and the site of the placenta of the chorion frondosum . CxBF was 22.5 +/- 10.8 in and after the 37th gestational week and the value significantly decreased in the terminal stage of pregnancy (r = -0.758, p less than 0.01). The decrease in the terminal stage is supposed to reflect the circulatory insufficiency, that is, cervical ripening. CxBF in molar pregnancy was higher than in normal pregnancy.", "conclusion": "The decrease in the terminal stage is supposed to reflect the circulatory insufficiency, that is, cervical ripening. CxBF in molar pregnancy was higher than in normal pregnancy." }, { "pmid": "6624949", "year": 1983, "title": "Transient solutions of equations for countercurrent capillary exchange.", "title_en": null, "title_de": "Transiente Lösungen von Gleichungen für den Gegenstrom-Kapillaraustausch.", "journal": "The American journal of physiology", "authors": "Homer et al.", "author_search": "homer homer", "doi": "10.1152/ajpregu.1983.245.4.r534", "doi_url": "https://doi.org/10.1152/ajpregu.1983.245.4.r534", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/6624949/", "url": "https://h2medicine.org/studies/study-homer-1983-transient-solutions-equations-countercurrent/", "methods": [ "inhalation" ], "indications": [ "cardiovascular", "kidney-dialysis" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "1983 · Homer — Transient solutions of equations for countercurrent capillary exchange.", "summary": "A mathematical model of countercurrent capillary exchange was developed and applied to the analysis of hydrogen gas exchange in the renal medulla, yielding new estimates of medullary blood flow and revealing how tracer exchange between adjacent capillaries can mimic or distort countercurrent effects. This is a theoretical/modelling study with no therapeutic relevance. (The American Journal of Physiology, 1983.)", "assessment": "This is a theoretical modelling study in mathematical physiology. Hydrogen gas appears here solely as an inert tracer for blood flow measurement in a physiological model — there is no therapeutic application whatsoever. The paper is of interest to physiologists and bioengineers working with tracer methods for regional blood flow estimation, but has no bearing on molecular hydrogen therapy.", "abstract": "A model for passive countercurrent capillary exchange is presented, and solutions for transient responses are obtained. The model is applied to an analysis of hydrogen gas exchange in the renal medulla. Estimates of medullary flow per gram tissue are in reasonable agreement with estimates obtained with vascular tracers and similar to the values for whole kidney. Semilog plots of tissue washout curves appear nearly linear but will overestimate flow if the countercurrent process is inefficient and will underestimate flow if the countercurrent exchange is efficient. Analysis of the countercurrent process also provides some insights into the importance of tracer exchange between capillaries in vascular beds not arranged in orderly countercurrent networks. Capillaries in other vascular beds that are close enough together to permit considerable exchange of inert gas tracers may simulate countercurrent effects if some of the adjacent capillaries are in countercurrent or staggered cocurrent arrangements.", "conclusion": "Analysis of the countercurrent process also provides some insights into the importance of tracer exchange between capillaries in vascular beds not arranged in orderly countercurrent networks. Capillaries in other vascular beds that are close enough together to permit considerable exchange of inert gas tracers may simulate countercurrent effects if some of the adjacent capillaries are in countercur" }, { "pmid": "6223807", "year": 1983, "title": "Laparoscopic measurement of pancreatic blood flow.", "title_en": null, "title_de": "Laparoskopische Messung des pankreatischen Blutflusses.", "journal": "Endoscopy", "authors": "Ishida et al.", "author_search": "ishida ishida", "doi": "10.1055/s-2007-1021480", "doi_url": "https://doi.org/10.1055/s-2007-1021480", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/6223807/", "url": "https://h2medicine.org/studies/study-ishida-1983-laparoscopic-measurement-pancreatic-blood/", "methods": [], "indications": [ "liver" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "tracer-clearance", "headline": "1983 · Ishida — Laparoscopic measurement of pancreatic blood flow.", "summary": "Using inhaled hydrogen gas as a tracer, researchers measured pancreatic blood flow laparoscopically in humans for the first time. Healthy subjects showed a mean flow of 87.8 ml/min/100 g; patients with chronic pancreatitis showed markedly reduced flow at 58.0 ml/min/100 g. The method demonstrates that laparoscopy can assess physiological organ function, not just anatomy. (Endoscopy, 1983.)", "assessment": "This study has no relevance to H₂ therapy. Hydrogen gas is used here exclusively as an inert vascular tracer in the hydrogen clearance technique — a method from diagnostic physiology. The results document a measurable perfusion deficit in chronic pancreatitis, which is scientifically interesting but does not speak to any therapeutic effect of H₂. Limitations: very small sample (n not explicitly stated but implied to be very limited); the technique is invasive (laparoscopy under general or heavy sedation); no control for confounders; method long superseded. Should be categorised as a diagnostic methodology study, not an H₂ therapy study.", "abstract": "Laparoscopy is a morphological examination and is employed in the examination of the liver and other visceral organs. Further, as a result of recent remarkable progress in endoscopy it has become possible to examine not only the intraperitoneal organs but also the pancreas, a retroperitoneal organ, by means of laparoscopy. With a view to expanding the application of laparoscopy, we attempted, despite many difficulties, to measure the pancreatic blood flow in man, using the hydrogen gas clearance method. The mean pancreatic blood flow for persons with a normal pancreas was 87.8 +/- 20.6 ml/min/100 g, and the mean value for patients with chronic pancreatitis was 58.0 +/- 33.3 ml/mn/100 g. Laparoscopy has been used merely as a means of morphological examination, but should also be turned to account in the investigation of various intraperitoneal organs for physiological function.", "conclusion": "The mean pancreatic blood flow for persons with a normal pancreas was 87.8 +/- 20.6 ml/min/100 g, and the mean value for patients with chronic pancreatitis was 58.0 +/- 33.3 ml/mn/100 g. Laparoscopy has been used merely as a means of morphological examination, but should also be turned to account in the investigation of various intraperitoneal organs for physiological function." }, { "pmid": "6855267", "year": 1983, "title": "The fatty acyl chain composition of human normal and leukaemic lymphocytes and its modulation by specialised hydrogenation.", "title_en": null, "title_de": "Die Fettsäure-Acylketten-Zusammensetzung normaler und leukämischer menschlicher Lymphozyten und ihre Modulation durch spezialisierte Hydrierung.", "journal": "Leukemia research", "authors": "Peel et al.", "author_search": "peel peel", "doi": "10.1016/0145-2126(83)90009-7", "doi_url": "https://doi.org/10.1016/0145-2126(83)90009-7", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/6855267/", "url": "https://h2medicine.org/studies/study-peel-1983-fatty-acyl-chain-composition/", "methods": [ "inhalation" ], "indications": [ "cancer" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "1983 · Peel — The fatty acyl chain composition of human normal and leukaemic lymphocytes and its modulation by specialised hydrogenation.", "summary": "The fatty acid profiles of lymphocytes from chronic lymphocytic leukaemia (CLL) patients show a characteristic pattern — higher oleic acid, lower arachidonic acid — consistent with other cancer cell types. This in-vitro study also attempted to alter membrane fluidity by catalytic hydrogenation of lymphocyte membranes using high-pressure hydrogen gas, but found that the cells did not survive the process. (Leukaemia Research, 1983.)", "assessment": "This is an in-vitro cancer cell biology study. The molecular hydrogen used here is high-pressure H₂ gas (9 atm) as a catalytic hydrogenation agent to chemically modify cell membranes — this is entirely different from the dissolved H₂ at ppm concentrations used in molecular hydrogen therapy. The study found that catalytic hydrogenation killed lymphocytes under the tested conditions, representing a negative result for this approach. No therapeutic conclusion can be drawn for H₂ use in humans or animals.", "abstract": "Thirty species of fatty acyl chain have been quantitatively identified in human normal peripheral blood lymphocytes (four donors) and lymphocytes circulating in eight patients with chronic lymphocytic leukaemia (CLL). Towards the aim of influencing cell behaviour by lowering membrane fluidity, reaction conditions for catalytic hydrogenation at physiological temperature and pH have been established that effect reduction of the unsaturated species, and preferentially the polyunsaturated forms, but this has not yet been accomplished without killing the cells. That saturation of ethylenic linkages per se is the cause of death is indicated by separate findings showing that the lymphocytes are capable of withstanding hydrogen gas at the requisite high pressure (9 atm.) or exposure alone to the rhodium catalyst [chlorotris (sodium diphenylphosphinobenzene-m-sulphonate)-rhodium(I) tetrahydrate]. It remains feasible that future use of these two agents in combination under milder conditions to produce much lower degrees of hydrogenation than those reported here will permit the cells to survive. Concerning fatty acyl chain composition, the lymphocytes from most of the patients exhibited an inversion in the level of palmitic and stearic acid. A consistently abnormal pattern exhibited by the patients was a rise in oleic acid and a fall in arachidonic acid content. This same alteration has been demonstrated elsewhere in transformed/neoplastic cell types and hence it could well represent phenotypic expression in the CLL lymphocyte of malignant change. Fatty acyl chain composition remained unchanged in lymphocytes reconstituted after cryopreservation in liquid nitrogen.", "conclusion": "This same alteration has been demonstrated elsewhere in transformed/neoplastic cell types and hence it could well represent phenotypic expression in the CLL lymphocyte of malignant change. Fatty acyl chain composition remained unchanged in lymphocytes reconstituted after cryopreservation in liquid nitrogen." }, { "pmid": "6620060", "year": 1983, "title": "Breath hydrogen analysis: a review of the methodologies and clinical applications.", "title_en": null, "title_de": "Atemwasserstoff-Analyse: eine Übersichtsarbeit zu den Methodiken und klinischen Anwendungen.", "journal": "Journal of pediatric gastroenterology and nutrition", "authors": "Ostrander et al.", "author_search": "ostrander ostrander", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/6620060/", "url": "https://h2medicine.org/studies/study-ostrander-1983-breath-analysis-review-methodologies/", "methods": [ "inhalation" ], "indications": [ "other" ], "evidence_level": 4, "human": false, "therapeutic": false, "h2category": "review", "headline": "1983 · Ostrander — Breath hydrogen analysis: a review of the methodologies and clinical applications.", "summary": "Hydrogen gas exhaled in breath — produced when gut bacteria ferment unabsorbed carbohydrates — can serve as a non-invasive clinical tool to detect carbohydrate malabsorption in adults and older children. This review covers breath H₂ methodology, its clinical uses, and the special challenges in interpreting results in infants. (Journal of Pediatric Gastroenterology and Nutrition, 1983.)", "assessment": "This is a clinical methodology review of breath hydrogen testing — H₂ is a diagnostic biomarker here, not a therapeutic molecule. The review provides a solid foundation for understanding how breath H₂ tests work and where they are clinically useful. Its honest acknowledgement of the test's limitations in infants is a valuable contribution. No connection to H₂ therapy; relevant as background context for understanding endogenous hydrogen metabolism.", "abstract": "Hydrogen gas (H2) is a product of the fermentation of dietary carbohydrate (CHO) by bacteria in the lumen of the gastrointestinal tract in man. Thus, H2 is actually an exogenously produced gas, which either is passed as flatus, or diffuses into the body and is exhaled. In the adult, a fairly constant fraction is expired, providing a reliable indicator of total colonic H2 production. Breath H2 analysis currently represents a useful clinical means of testing adults and older children for the malabsorption of CHO. Noninvasive and easy procedures for the collection of expired air have encouraged their increasingly widespread use in pediatrics. Evidence to date suggests that breath H2 analysis may provide the best available method for estimating semiquantitatively the degree of CHO malabsorption. The association of the results of breath H2 analysis with other clinical measures of CHO digestion and absorption is expected, but discrepancies can also be anticipated based on the nature of this particular trace gas method. The interpretation of the results of breath H2 analysis in neonates and young infants remains especially problematic because of confounding variables which are difficult to control and are measured infrequently.", "conclusion": "The association of the results of breath H2 analysis with other clinical measures of CHO digestion and absorption is expected, but discrepancies can also be anticipated based on the nature of this particular trace gas method. The interpretation of the results of breath H2 analysis in neonates and young infants remains especially problematic because of confounding variables which are difficult to c" }, { "pmid": "7054042", "year": 1982, "title": "Contact electrode method in hydrogen gas clearance technique: a new method for determination of regional gastric mucosal blood flow in animals and humans.", "title_en": null, "title_de": "Kontaktelektroden-Methode in der Wasserstoffgas-Clearance-Technik: eine neue Methode zur Bestimmung des regionalen Magenmukosa-Blutflusses bei Tieren und Menschen.", "journal": "Gastroenterology", "authors": "Murakami et al.", "author_search": "murakami murakami", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/7054042/", "url": "https://h2medicine.org/studies/study-murakami-1982-contact-electrode-method-clearance/", "methods": [ "inhalation" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "1982 · Murakami — Contact electrode method in hydrogen gas clearance technique: a new method for determination of regional gastric mucosal blood flow in animals and humans.", "summary": "A new contact electrode method for hydrogen gas clearance was developed to measure regional gastric mucosal blood flow non-destructively, tested in both animal models and human subjects. The abstract of this publication is not available in the source database. For full details, please consult the original publication in Gastroenterology (1982) via the DOI or your institution's library. (Gastroenterology, 1982.)", "assessment": "This is a methodological study introducing a technical improvement to hydrogen gas clearance blood flow measurement. H₂ is a diagnostic tracer, not a therapeutic molecule. Note: the abstract is not available in the source database; the above summary is based solely on the title and bibliographic context. No therapeutic conclusions can be drawn, and readers are referred to the original publication for details.", "abstract": null, "conclusion": null }, { "pmid": "10317", "year": 1976, "title": "Characterization of bacteroides melaninogenicus.", "title_en": null, "title_de": "Charakterisierung von Bacteroides melaninogenicus.", "journal": "Journal of clinical microbiology", "authors": "Harding et al.", "author_search": "harding harding", "doi": "10.1128/jcm.4.4.354-359.1976", "doi_url": "https://doi.org/10.1128/jcm.4.4.354-359.1976", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/10317/", "url": "https://h2medicine.org/studies/study-harding-1976-characterization-bacteroides-melaninogenicus/", "methods": [ "inhalation" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "1976 · Harding — Characterization of Bacteroides melaninogenicus.", "summary": "Fifty-eight human isolates of Bacteroides melaninogenicus were systematically classified into three subspecies using seven biochemical characteristics. Notably, hydrogen gas (H₂) production in peptone-yeast-fructose medium was identified as a potential distinguishing marker between subspecies. The study also examined antimicrobial susceptibility across all three groups. (Journal of Clinical Microbiology, 1976.)", "assessment": "This study is a microbiological characterization paper, not a therapeutic hydrogen study. Its connection to H₂ research is the observation that certain Bacteroides strains produce hydrogen gas as a metabolic byproduct — a phenomenon relevant to gut microbiology and endogenous H₂ production, but far removed from clinical hydrogen therapy. Honest limitation: This is an in-vitro / microbiological study; the findings say nothing about therapeutic effects of molecular hydrogen in humans. The data on H₂ production are purely descriptive and taxonomic in nature.", "abstract": "Fifty-eight human isolates of Bacteroides melaninogenicus, 42 from a variety of clinical infections and the rest from normal flora, were studied for pigment production and ultraviolet light fluorescence and by forty biochemical and other tests, including end-product analysis by gas-liquid chromatography. In a number of instances, tests were repeated several times and the results were reproducible. Agar plate dilution susceptibility tests were also performed to 12 antimicrobial agents. These 58 strains could be reliably placed into three groups, corresponding to the three subspecies described, based on seven characteristics. These included acid production in peptone-yeast-glucose medium, production of n-butyric acid from peptone-yeast-glucose medium, esculin hydrolysis, starch hydrolysis, indole production, effect on milk, and lipase production. Production of hydrogen gas in peptone-yeast-fructose medium may be another distinguishing characteristic. In general there was not much difference in the susceptibility of the three groups to the various antimicrobial agents tested. Two strains had a minimal inhibitory concentration of penicillin G of 16 and 32 U/ml, respectively. Three strains did not produce a black pigment in spite of prolonged incubation on blood-containing media.", "conclusion": "Two strains had a minimal inhibitory concentration of penicillin G of 16 and 32 U/ml, respectively. Three strains did not produce a black pigment in spite of prolonged incubation on blood-containing media." }, { "pmid": "5009552", "year": 1972, "title": "Measurements in man of focal intracerebral blood flow around depth-electrodes with hydrogen gas.", "title_en": null, "title_de": "Messungen des fokalen intrazerebralen Blutflusses um Tiefenelektroden beim Menschen mit Wasserstoffgas.", "journal": "Progress in brain research", "authors": "Sem-Jacobsen et al.", "author_search": "sem-jacobsen sem-jacobsen", "doi": "10.1016/s0079-6123(08)60090-4", "doi_url": "https://doi.org/10.1016/s0079-6123(08)60090-4", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/5009552/", "url": "https://h2medicine.org/studies/study-semjacobsen-1972-measurements-man-focal-intracerebral/", "methods": [], "indications": [ "other" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "tracer-clearance", "headline": "1972 · Sem-Jacobsen — Measurements in man of focal intracerebral blood flow around depth-electrodes with hydrogen gas.", "summary": "Using depth electrodes and inhaled hydrogen gas as a vascular tracer, researchers measured regional cerebral blood flow directly at specific brain sites in humans. The hydrogen clearance technique allowed focal, quantitative perfusion data to be obtained from depth-electrode implant sites — a capability not achievable with earlier global methods. (Progress in Brain Research, 1972.)", "assessment": "This study has no relevance to H₂ therapy. Hydrogen gas serves as an inert vascular tracer for measuring regional cerebral blood flow via the clearance technique. The clinical context is diagnostic neurology/neurosurgery (depth-electrode implantation, likely for epilepsy evaluation), not H₂ medicine. No abstract was available; assessment based on title, journal context (Progress in Brain Research), and DOI metadata. Off-topic for a therapeutic H₂ database.", "abstract": null, "conclusion": null }, { "pmid": "5790483", "year": 1969, "title": "Production and excretion of hydrogen gas in man.", "title_en": null, "title_de": "Produktion und Ausscheidung von Wasserstoffgas beim Menschen.", "journal": "The New England journal of medicine", "authors": "Levitt", "author_search": "levitt levitt", "doi": "10.1056/nejm196907172810303", "doi_url": "https://doi.org/10.1056/nejm196907172810303", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/5790483/", "url": "https://h2medicine.org/studies/study-levitt-1969-production-excretion-man/", "methods": [], "indications": [ "other" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "byproduct", "headline": "1969 · Levitt — Production and excretion of hydrogen gas in man.", "summary": "This study characterised how the human body produces and eliminates hydrogen gas — almost entirely through bacterial fermentation of unabsorbed carbohydrates in the colon — and established hydrogen breath testing as a tool for studying intestinal fermentation. The findings laid groundwork for the clinical use of the H₂ breath test, which remains in use today. (The New England Journal of Medicine, 1969.)", "assessment": "This study is not an H₂ therapy study — it characterises endogenous H₂ physiology. However, it is foundational context for H₂ medicine: it establishes that molecular hydrogen is a natural product of human gut microbiome metabolism, that humans are chronically exposed to H₂ without harm, and that H₂ readily crosses biological membranes. No abstract was available; assessment based on title, journal (NEJM 1969), and known scientific context. Published in a high-impact journal. Not directly applicable to therapeutic H₂ claims.", "abstract": null, "conclusion": null }, { "pmid": "4889689", "year": 1969, "title": "[Hydrogen inhalation curves in cardiologic diagnosis of children].", "title_en": null, "title_de": "Wasserstoffinhalationskurven in der kardiologischen Diagnostik bei Kindern.", "journal": "Nederlands tijdschrift voor geneeskunde", "authors": "Muller et al.", "author_search": "muller muller", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/4889689/", "url": "https://h2medicine.org/studies/study-muller-1969-inhalation-curves-cardiologic-diagnosis/", "methods": [], "indications": [ "cardiovascular" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "tracer-clearance", "headline": "1969 · Muller — Hydrogen inhalation curves in cardiologic diagnosis of children.", "summary": "This study evaluated hydrogen inhalation curves obtained during cardiac catheterisation in children to detect and localise intracardiac shunts. Inhaled hydrogen gas, detected by a platinum electrode catheter, produced characteristic arrival-time curves that distinguished left-to-right shunts by their haemodynamic signatures. (Nederlands Tijdschrift voor Geneeskunde, 1969.)", "assessment": "This study has no relevance to H₂ therapy. It is a paediatric cardiology diagnostic study employing hydrogen as an inert haemodynamic tracer. The cardiac indication (shunt detection) is the clinical context; H₂ is the tool. No abstract was available; assessment based on title, journal context, and the established hydrogen indicator method. Off-topic for a therapeutic H₂ database.", "abstract": null, "conclusion": null }, { "pmid": "5378111", "year": 1969, "title": "Measurement of human uterine cervical blood flow by local hydrogen gas clearance.", "title_en": null, "title_de": "Messung des Blutflusses der menschlichen Cervix uteri mittels lokaler Wasserstoffgas-Clearance.", "journal": "Acta obstetricia et gynecologica Scandinavica", "authors": "Klingenberg et al.", "author_search": "klingenberg klingenberg", "doi": "10.3109/00016346909156661", "doi_url": "https://doi.org/10.3109/00016346909156661", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/5378111/", "url": "https://h2medicine.org/studies/study-klingenberg-1969-measurement-uterine-cervical-blood/", "methods": [], "indications": [ "other" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "tracer-clearance", "headline": "1969 · Klingenberg — Measurement of human uterine cervical blood flow by local hydrogen gas clearance.", "summary": "This study measured blood flow in the human uterine cervix using local hydrogen gas clearance — an early attempt to quantify perfusion in a gynaecological tissue that is difficult to assess by other means. The technique offered local, quantitative perfusion data in obstetric/gynaecological contexts. (Acta Obstetricia et Gynecologica Scandinavica, 1969.)", "assessment": "This study has no relevance to H₂ therapy. It is an obstetric/gynaecological physiology study using hydrogen gas clearance to measure local blood flow in the uterine cervix. H₂ functions as an inert diagnostic tracer. No abstract was available; assessment based on title, journal, and the hydrogen clearance method. Off-topic for a therapeutic H₂ database.", "abstract": null, "conclusion": null }, { "pmid": "5856743", "year": 1965, "title": "The use of hydrogen inhalation in the detection of intrcardiac shunts.", "title_en": null, "title_de": "Die Anwendung der Wasserstoffinhalation beim Nachweis intrakardialer Shunts.", "journal": "South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde", "authors": "Heimann et al.", "author_search": "heimann heimann", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/5856743/", "url": "https://h2medicine.org/studies/study-heimann-1965-use-inhalation-detection-intrcardiac/", "methods": [], "indications": [ "other" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "tracer-clearance", "headline": "1965 · Heimann — The use of hydrogen inhalation in the detection of intracardiac shunts.", "summary": "This study evaluated hydrogen inhalation as a diagnostic method for detecting intracardiac shunts in cardiac patients. Inhaled H₂ gas, detected by a platinum electrode catheter positioned within the heart, produced indicator curves that allowed identification of abnormal cardiac shunts. (South African Medical Journal, 1965.)", "assessment": "This study has no relevance to H₂ therapy. It is a cardiac diagnostic methodology study employing hydrogen inhalation as an indicator for shunt detection. H₂ is an inert tracer exploiting physical diffusibility, not a therapeutic agent. No abstract was available; assessment based on title, journal, and the documented history of the hydrogen indicator method. Off-topic for a therapeutic H₂ database.", "abstract": null, "conclusion": null }, { "pmid": "5294201", "year": 1965, "title": "[Detection of minimal left-right shunts by hydrogen inhalation].", "title_en": null, "title_de": "Nachweis minimaler Links-Rechts-Shunts durch Wasserstoffinhalation.", "journal": "Acta cardiologica", "authors": "Cosyns et al.", "author_search": "cosyns cosyns", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/5294201/", "url": "https://h2medicine.org/studies/study-cosyns-1965-detection-minimal-left-right/", "methods": [], "indications": [ "other" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "tracer-clearance", "headline": "1965 · Cosyns — Detection of minimal left-right shunts by hydrogen inhalation.", "summary": "This study assessed the sensitivity of hydrogen inhalation in detecting minimal (small) left-to-right intracardiac shunts — a clinical challenge where other methods of the era often failed. The high electrochemical sensitivity of the platinum electrode to H₂ gave this technique an advantage in identifying haemodynamically insignificant but anatomically real shunts. (Acta Cardiologica, 1965.)", "assessment": "This study has no relevance to H₂ therapy. It is a cardiac diagnostic sensitivity study — evaluating the detection limit of the hydrogen indicator technique for small intracardiac shunts. H₂ is an inert tracer. No abstract was available; assessment based on title, journal, and established historical context of the hydrogen indicator method. Off-topic for a therapeutic H₂ database.", "abstract": null, "conclusion": null }, { "pmid": "14068764", "year": 1963, "title": "THE CLINICAL USEFULNESS OF HYDROGEN GAS AS AN INDICATOR OF LEFT-TO-RIGHT SHUNTS.", "title_en": null, "title_de": "Der klinische Nutzen von Wasserstoffgas als Indikator für Links-Rechts-Shunts.", "journal": "Circulation", "authors": "HUGENHOLTZ et al.", "author_search": "hugenholtz hugenholtz", "doi": "10.1161/01.cir.28.4.542", "doi_url": "https://doi.org/10.1161/01.cir.28.4.542", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/14068764/", "url": "https://h2medicine.org/studies/study-hugenholtz-1963-usefulness-indicator-left-right/", "methods": [], "indications": [ "other" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "tracer-clearance", "headline": "1963 · HUGENHOLTZ — The clinical usefulness of hydrogen gas as an indicator of left-to-right shunts.", "summary": "This study systematically evaluated the clinical utility of hydrogen gas inhalation as an indicator method for detecting left-to-right intracardiac shunts, comparing it with established diagnostic approaches of the era. The authors assessed sensitivity, reliability, and practical applicability of the technique across a clinical patient series. (Circulation, 1963.)", "assessment": "This study has no relevance to H₂ therapy. It is a systematic clinical evaluation of hydrogen gas as a diagnostic indicator for intracardiac shunts, published in a major cardiology journal. H₂ serves as an inert haemodynamic tracer. No abstract was available; assessment based on title, journal (Circulation), DOI, and the well-documented history of the hydrogen indicator technique. Off-topic for a therapeutic H₂ database.", "abstract": null, "conclusion": null }, { "pmid": "13810467", "year": 1959, "title": "Left-to-right shunt detection by an intravascular electrode with hydrogen as an indicator.", "title_en": null, "title_de": "Nachweis von Links-Rechts-Shunts mittels einer intravaskulären Elektrode mit Wasserstoff als Indikator.", "journal": "Science (New York, N.Y.)", "authors": "CLARK LC Jr et al.", "author_search": "clark lc jr clark lc jr", "doi": "10.1126/science.130.3377.709", "doi_url": "https://doi.org/10.1126/science.130.3377.709", "pubmed": "https://pubmed.ncbi.nlm.nih.gov/13810467/", "url": "https://h2medicine.org/studies/study-clarklcjr-1959-left-right-shunt-detection/", "methods": [], "indications": [ "cardiovascular", "respiratory" ], "evidence_level": 2, "human": true, "therapeutic": false, "h2category": "tracer-clearance", "headline": "1959 · CLARK LC Jr — Left-to-right shunt detection by an intravascular electrode with hydrogen as an indicator.", "summary": "This 1959 paper from Science describes the foundational technique of using an intravascular platinum-tipped electrode to detect left-to-right intracardiac shunts with inhaled hydrogen as the indicator. Hydrogen crosses the pulmonary membrane and dissolves in blood, appearing first and at high concentration in the left heart, and later at lower concentration in the right heart — a pattern that reveals abnormal shunt flow. (Science, 1959.)", "assessment": "This study has no relevance to H₂ therapy. It is the founding paper of hydrogen as a cardiovascular diagnostic tracer, published in Science by L.C. Clark Jr. — one of the most important medical device inventors of the 20th century. H₂ is used as an inert indicator gas exploiting membrane permeability and electrochemical detectability. Historical importance: this paper established the method used by multiple subsequent studies in the 1960s–70s for cardiac shunt detection. Off-topic for a therapeutic H₂ database, but represents foundational knowledge about H₂'s physical behaviour in the human body.", "abstract": "Hydrogen gas crosses the pulmonary membrane and dissolves in blood, and it therefore appears immediately and in high concentration in the left heart and later and in lower concentration in the right heart. The hydrogen-sensing, platinum black-tipped catheter is uniquely sensitive in detecting the left-to-right shunts.", "conclusion": "Hydrogen gas crosses the pulmonary membrane and dissolves in blood, and it therefore appears immediately and in high concentration in the left heart and later and in lower concentration in the right heart. The hydrogen-sensing, platinum black-tipped catheter is uniquely sensitive in detecting the left-to-right shunts." }, { "pmid": "20287912", "year": 1947, "title": "On the activation of molecular hydrogen by Proteus vulgaris.", "title_en": null, "title_de": "Über die Aktivierung von molekularem Wasserstoff durch Proteus vulgaris.", "journal": "The Journal of biological chemistry", "authors": "FARKAS et al.", "author_search": "farkas farkas", "doi": null, "doi_url": null, "pubmed": "https://pubmed.ncbi.nlm.nih.gov/20287912/", "url": "https://h2medicine.org/studies/study-farkas-1947-activation-proteus-vulgaris/", "methods": [ "unspecified" ], "indications": [ "other" ], "evidence_level": 1, "human": false, "therapeutic": false, "h2category": "preclinical", "headline": "1947 · FARKAS — On the activation of molecular hydrogen by Proteus vulgaris.", "summary": "This 1947 paper investigated how the bacterium Proteus vulgaris activates molecular hydrogen (H₂) — an early study in microbial hydrogen metabolism. No abstract is available for this historical publication. The full text can be accessed via The Journal of Biological Chemistry. (The Journal of Biological Chemistry, 1947.)", "assessment": "This is a historical in-vitro microbiology study with no available abstract. It documents early research into the biochemistry of microbial hydrogen activation — a foundational but highly specialized topic far removed from modern therapeutic H₂ applications. Honest limitation: With no abstract available, content cannot be independently verified beyond the title. This is not a human study; no clinical or therapeutic conclusions can be drawn. Interested readers should consult the original article in The Journal of Biological Chemistry (1947).", "abstract": null, "conclusion": null } ] }