Fundamentals / Safety
Fundamentals and safety: studies on tolerability, dosing, pharmacokinetics and measurement methods of H₂ in humans.
Human studies on molecular hydrogen for Fundamentals / Safety. This page collects the 57 studies catalogued in this area — 8 randomized trials, 13 pilot/observational studies and 17 reviews. Listed newest first.
2026 · Nguyen — Advances in hydrogen delivery strategies for therapeutic applications
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.
2026 · Pan — Stimuli-Responsive Hydrogen Production from Nanomaterials: Design, Regulation and Biomedical Applications
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.
2025 · Xie — Mechanisms and Protective Strategies for Astronaut Skin Injury in Deep Space Environments
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.
2025 · Bilski — Antioxidant Therapies as Emerging Adjuncts in Rheumatoid Arthritis: Targeting Oxidative Stress to Enhance Treatment Outcomes
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.
2025 · Neykhonji — Exploring the Potential of H₂ Therapy in Reducing Surgical Complications: A Review on Anti-inflammatory, Antioxidant, and Anti-fibrotic Mechanisms
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.
2025 · Li — Application Trends of Hydrogen-generating Nanomaterials for the Treatment of ROS-related Diseases
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).
2024 · Khiji — The Therapeutic Application of Hydrogen in Cancer: The Potential and Challenges
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.
2022 · Ahmad et al. — Narrative on Hydrogen Therapy and its Clinical Applications: Safety and Efficacy
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.
2021 · Hirano — Molecular Hydrogen as a Novel Antitumor Agent: Possible Mechanisms Underlying Gene Expression.
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.
2021 · Magliocca et al. — Inhaled gases as novel neuroprotective therapies in the postcardiac arrest period.
After cardiac arrest, inhaled gases such as xenon, argon, nitric oxide, and molecular hydrogen (H₂) have shown neuroprotective properties in experimental models.
2021 · Shi et al. — Hydrogen treatment: a novel option in liver diseases.
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.
2021 · Li et al. — Hydrogen Commonly Applicable from Medicine to Agriculture: From Molecular Mechanisms to the Field.
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.
2021 · Domoki — Hydrogen-induced Neuroprotection in Neonatal Hypoxic-ischemic Encephalopathy.
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.
2021 · Htun et al. — Hydrogen and Therapeutic Gases for Neonatal Hypoxic-Ischemic Encephalopathy: Potential Neuroprotective Adjuncts in Translational Research
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.
2019 · Wu — Hydrogen Gas from Inflammation Treatment to Cancer Therapy
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.
2013 · Zheng — Equol: a metabolite of soy isoflavones by intestinal microflora — a review
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.
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
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.
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.
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.
2018 · Jin — Clinical Study of Hydrogen-Rich Saline in the Treatment of Moderate to Severe Allergic Rhinitis
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.
2018 · Korovljev — Molecular Hydrogen Affects Body Composition, Metabolic Profiles, and Mitochondrial Function in Middle-Aged Overweight Women
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.
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
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.
2017 · Ono et al. — Hydrogen Gas Inhalation Treatment in Acute Cerebral Infarction: A Randomized Controlled Clinical Study on Safety and Neuroprotection.
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).
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.
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.
2014 · Ishibashi et al. — Therapeutic efficacy of infused molecular hydrogen in saline on rheumatoid arthritis: a randomized, double-blind, placebo-controlled pilot study.
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.
2025 · Habet et al. — Hydrogen-FAST: Study Protocol for Inhaled Hydrogen Gas as Adjunctive Therapy in Refractory Cardiac Arrest (ECPR)
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.
2024 · Lin — Early Hydrogen-Oxygen Gas Mixture Inhalation in Patients with Aneurysmal Subarachnoid Hemorrhage (HOMA): study protocol for a randomized controlled trial.
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.
2024 · Liu — The Benefit of Hydrogen Gas as an Adjunctive Therapy for Chronic Obstructive Pulmonary Disease.
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.
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.
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.
2022 · Tanaka — Hydrogen-rich bath with nano-sized bubbles improves antioxidant capacity and inflammation levels in human serum
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.
2021 · Sugaya — Association of Breath Hydrogen Concentration with Oral Intake and Urinary Diseases
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.
2020 · Asada et al. — Effects of hydrogen-rich water prepared by alternating-current-electrolysis on antioxidant activity, DNA oxidative injuries, and diabetes-related markers.
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.
2016 · Tamura et al. — Feasibility and Safety of Hydrogen Gas Inhalation for Post-Cardiac Arrest Syndrome — First-in-Human Pilot Study.
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.
2004 · Nakamura et al. — Bioavailability of Cellobiose by Tolerance Test and Breath Hydrogen Excretion in Humans
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.
1985 · Solomons et al. — Intestinal Metabolism of a Random-Bonded Polyglucose Bulking Agent in Humans: In Vitro and In Vivo Studies of Hydrogen Evolution
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.
2026 · Yang — Molecular hydrogen suppresses gut inflammation and pyroptosis in ulcerative colitis through promoting PKM2 lactylation to block NLRP3 inflammasome activation.
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.
2026 · Yano — Electrolyzed Hydrogen Water Improves Chemosensitivity to Anticancer Drugs by Potently Suppressing Autophagy
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.
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
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.
2025 · Qiu — 3D printing combined with pH-induced 4D printed iron(III)-oxidized starch gels for controlled iron delivery and enhanced iron supplementation.
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.
2025 · Chen — A Sustained H₂/Fluorouracil-Releasing Suppository for High-efficacy and Low-Toxicity Hydrogenochemotherapy of Colon Cancer.
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.
2025 · Zhang — Living Therapeutics for Synergistic Hydrogen-Photothermal Cancer Treatment by Photosynthetic Bacteria.
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.
2023 · Son — PdO-Nanoparticle-Embedded Carbon Nanotube Yarns for Wearable Hydrogen Gas Sensing Platforms with Fast and Sensitive Responses
Researchers developed a flexible yarn-type sensor that detects explosive hydrogen concentrations within two seconds — opening a path toward wearable H₂ safety monitors.
2023 · Zhu — Two-Dimensional Mg₂Si Nanosheet-Enabled Sustained Hydrogen Generation for Improved Repair and Regeneration of Deeply Burned Skin
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.
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
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%.
2022 · Li — Local Treatment of Hydrogen-Rich Saline Promotes Wound Healing In Vivo by Inhibiting Oxidative Stress via Nrf-2/HO-1 Pathway
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.
2022 · Ge — Microbial hydrogen economy alleviates colitis by reprogramming colonocyte metabolism and reinforcing intestinal barrier
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.
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
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.
2021 · van Gelder et al. — Safety of Electrooxidation for Urea Removal in a Wearable Artificial Kidney Is Compromised by Formation of Glucose Degradation Products
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.
2020 · Wang — NIR-Driven Water Splitting H₂ Production Nanoplatform for H₂-Mediated Cascade-Amplifying Synergetic Cancer Therapy
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.
2019 · Kou et al. — Acid-responsive H₂-releasing Fe nanoparticles for safe and effective cancer therapy.
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.
2019 · Kobayashi — Organ Preservation Solution Containing Dissolved Hydrogen Gas from a Hydrogen-Absorbing Alloy Canister Improves Function of Transplanted Ischemic Kidneys in Miniature Pigs
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.
2018 · Tamaki — Hydrogen Flush After Cold Storage as a New End-Ischemic Ex Vivo Treatment for Liver Grafts Against Ischemia/Reperfusion Injury
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.
2018 · Wan — An In Situ Depot for Continuous Evolution of Gaseous H₂ Mediated by a Magnesium Passivation/Activation Cycle for Treating Osteoarthritis
This mouse study tested intra-muscular injection of magnesium-containing microparticles (Mg@PLGA) as a local H₂ delivery system for osteoarthritis (OA).
2016 · Davoren — Design and Optimization of Selective Azaindole Amide M1 Positive Allosteric Modulators
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.