Neurology
Studies on the brain and nervous system (for example after oxygen deprivation or on cognitive questions), in which H₂ is examined as a possible protective factor. Neurology is among the more actively researched fields: around 140 papers touch on this topic, including about 12 randomized controlled trials and around 24 pilot and observational studies in humans, supplemented by numerous reviews as well as mechanistic and preclinical investigations.
The questions range from the state after cardiac arrest and stroke through Parkinson’s disease to cognitive and mood-related endpoints. The studies mainly examined inhalation of H₂ gas and hydrogen-rich water; the target measures were neurological scales, imaging, cognitive tests and markers of oxidative stress.
Some studies report favorable signals, for example in recovery after oxygen deprivation; others show no clear effect. Because of small samples, differing disease pictures and heterogeneous protocols, the evidence is preliminary and inconsistent — an established therapeutic benefit cannot be derived from it.
Human studies on molecular hydrogen for Neurology. This page collects the 140 studies catalogued in this area — 12 randomized trials, 24 pilot/observational studies and 57 reviews. Listed newest first.
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?
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.
2026 · Dumbuya — The protective effects of molecular hydrogen in sepsis-associated encephalopathy: current status.
Sepsis-associated encephalopathy (SAE) — brain dysfunction that develops during severe infections — currently has no specific approved therapy.
2026 · Paparella — Medical Gases as Emerging Regulators of Paediatric Endocrine and Neurodevelopmental Pathways: A Mini-Review
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.
2026 · Nguyen Puente — Emerging Clinical Applications for Molecular Hydrogen
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.
2026 · Merigo — Gas Therapies for Neuro-Protection
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.
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 · Brandi — Molecular hydrogen therapy: A „democratic” emerging strategy against aging and age-related diseases
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.
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).
2025 · Todorović — Hydrogen as an Innovative Nootropic in Health and Disease
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.
2024 · Dhillon — Hydrogen Water: Extra Healthy or a Hoax?—A Systematic Review
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.
2024 · Slezák — New Possibilities of the Prevention and Treatment of Cardiovascular Pathologies: The Potential of Molecular Hydrogen in the Reduction of Oxidative Stress
This review examines molecular hydrogen (H₂) as a selective antioxidant with particular promise for cardiovascular disease, where oxidative stress plays a defining role.
2024 · Kura — The Protective Role of Molecular Hydrogen in Ischemia/Reperfusion Injury
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.
2024 · Tsuzuki — Idiopathic Sudden Sensorineural Hearing Loss: A Review Focused on the Contribution of Vascular Pathologies
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.
2023 · Kuo — Molecular Hydrogen: Emerging Treatment for Stroke Management
Molecular hydrogen (H₂) is an emerging therapeutic approach in ischemic stroke — antioxidative, anti-inflammatory and anti-apoptotic.
2023 · He et al. — The Role of Hydrogen Therapy in Alzheimer's Disease Management: Insights into Mechanisms, Administration Routes, and Future Challenges
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.
2023 · Wu et al. — Molecular Hydrogen: An Emerging Therapeutic Medical Gas for Brain Disorders
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.
2022 · Biswas — Electrocoagulation and electrooxidation technologies for pesticide removal from water or wastewater: A review
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.
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 · Noda — Neuroprotective and Preventative Effects of Molecular Hydrogen
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.
2021 · Oren — Amyloid β structural polymorphism, associated toxicity and therapeutic strategies.
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.
2021 · Schönfeld — How the brain fights fatty acids' toxicity.
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.
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 · 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 · Ohta — Direct Targets and Subsequent Pathways for Molecular Hydrogen to Exert Multiple Functions: Focusing on Interventions in Radical Reactions
Molecular hydrogen (H₂) is not simply a passive antioxidant — it actively intervenes in radical chain reactions, modifying lipid peroxides and downstream signaling cascades.
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.
2021 · Ostojic — Hydrogen as a Potential Therapeutic in Obesity: Targeting the Brain
This short review considers whether molecular H₂ could act directly on brain structures involved in obesity regulation — particularly the hypothalamus.
2021 · Lucas — Molecular hydrogen (H₂) as a potential treatment for acute and chronic fatigue
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.
2021 · Huang et al. — Molecular Hydrogen Application in Stroke: Bench to Bedside
This review summarises experimental and clinical evidence on molecular hydrogen (H₂) therapy in stroke, covering both animal models and human studies.
2020 · Wang — Prospects of molecular hydrogen in perioperative neuroprotection from basic research to clinical application
This systematic review summarizes why molecular hydrogen is being researched as neuroprotection around surgery: antioxidant, anti-inflammatory, antiapoptotic and mitochondria-protective effects.
2020 · Kawamura et al. — Application of Molecular Hydrogen as a Novel Antioxidant in Sports Science
This review surveys the evidence on molecular hydrogen (H₂) intake and exercise, covering all administration routes and focusing on exercise-induced oxidative stress.
2019 · Morris — Myalgic encephalomyelitis/chronic fatigue syndrome: From pathophysiological insights to novel therapeutic opportunities.
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.
2019 · LeBaron et al. — A New Approach for the Prevention and Treatment of Cardiovascular Disorders. Molecular Hydrogen Significantly Reduces the Effects of Oxidative Stress.
Molecular hydrogen (H₂) has been studied in preclinical and clinical settings for a wide range of cardiovascular conditions linked to oxidative stress and inflammation.
2019 · Noda et al. — Circulating messenger for neuroprotection induced by molecular hydrogen.
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.
2019 · Ishibashi — Therapeutic Efficacy of Molecular Hydrogen: A New Mechanistic Insight.
Beyond scavenging hydroxyl radicals, molecular hydrogen (H₂) may act directly on mitochondrial complex I — the enzyme that drives cellular energy production.
2019 · Cejka et al. — The preventive and therapeutic effects of molecular hydrogen in ocular diseases and injuries where oxidative stress is involved.
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.
2019 · Li et al. — Hydrogen as a complementary therapy against ischemic stroke: A review of the evidence.
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.
2019 · Wang et al. — Neonatal hypoxic-ischemic encephalopathy: emerging therapeutic strategies based on pathophysiologic phases of the injury.
This 2019 review proposes a phase-based treatment framework for neonatal hypoxic-ischemic encephalopathy (HIE), a major cause of infant death and disability.
2018 · Morris — The putative role of oxidative stress and inflammation in the pathophysiology of sleep dysfunction across neuropsychiatric disorders
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.
2017 · Iketani — Molecular Hydrogen as a Neuroprotective Agent
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.
2016 · Zheng — Molecular Hydrogen Therapy Ameliorates Organ Damage Induced by Sepsis
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.
2015 · Ostojic — Molecular hydrogen in sports medicine: new therapeutic perspectives.
Molecular hydrogen (H₂) may offer a novel approach for addressing exercise-induced oxidative stress and sports injuries, with potential to also improve exercise performance.
2014 · Fernández-Gajardo et al. — Novel therapeutic strategies for traumatic brain injury: acute antioxidant reinforcement.
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.
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
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.
2013 · Lucas — Role of the Toll Like receptor (TLR) radical cycle in chronic inflammation: possible treatments targeting the TLR4 pathway
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.
2012 · Ohno et al. — Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases.
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.
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.
Oxidative stress and reactive oxygen species (ROS) are implicated in many major diseases including inflammation, diabetes, glaucoma, cancer, ischemia, and neurodegeneration.
2011 · Naeem et al. — Defective protein folding and aggregation as the basis of neurodegenerative diseases: the darker aspect of proteins.
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.
2011 · Acuña Castroviejo — Melatonin-Mitochondria Interplay in Health and Disease
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.
2010 · Hong — Research Advances on Hydrogen Therapy in Nervous System Diseases
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.
2010 · Shen — Hydrogen as a novel and effective treatment of acute carbon monoxide poisoning.
This hypothesis paper proposes that inhaled molecular hydrogen (H₂) could be an effective treatment for acute carbon monoxide (CO) poisoning.
2002 · Acuña Castroviejo et al. — Melatonin, mitochondrial homeostasis and mitochondrial-related diseases
This review covers melatonin's antioxidant role in protecting mitochondria from reactive oxygen species (ROS), and its potential relevance to neurodegenerative and neuromuscular diseases.
1996 · Mehta — Magnetization Transfer Magnetic Resonance Imaging: A Clinical Review
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.
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
Hydrogen-rich water curbs food cravings and raises the satiety hormone GLP-1 in obese people.
2023 · Lin — Hydrogen Gas Treatment Improves Postoperative Delirium and Cognitive Dysfunction in Elderly Noncardiac Patients
Prophylactic hydrogen inhalation nearly halves postoperative delirium in elderly patients.
2021 · Takeuchi — Intravenous Hydrogen Therapy With Intracisternal Magnesium Sulfate Infusion in Severe Aneurysmal Subarachnoid Hemorrhage
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.
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
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.
2018 · Yoritaka — Randomized, Double-Blind, Multicenter Trial of Hydrogen Water for Parkinson's Disease
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.
2018 · Nishimaki — Effects of Molecular Hydrogen Assessed by an Animal Model and a Randomized Clinical Study on Mild Cognitive Impairment
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.
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).
2016 · Yoritaka et al. — A randomized double-blind multi-center trial of hydrogen water for Parkinson's disease: protocol and baseline characteristics.
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.
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.
2013 · Yoritaka et al. — Pilot study of H₂ therapy in Parkinson's disease: a randomized double-blind placebo-controlled trial.
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.
2026 · Li — Adjunctive Molecular Hydrogen Capsule Therapy in Empyema Complicated by Chronic Inflammatory Demyelinating Polyneuropathy: A Case Report
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.
2025 · Moriya et al. — Hydrogen Inhalation Is Associated With a Transient Rightward Shift in Prefrontal Oxyhemoglobin Asymmetry and Autonomic Modulation
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.
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.
2025 · Tu et al. — Molecular Hydrogen Therapy in Rheumatoid Arthritis: A Case Report on the Amelioration of Methotrexate-induced Myelosuppression and Immune Modulation
Methotrexate (MTX) is essential for rheumatoid arthritis but can cause dangerous bone marrow suppression.
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
Acute subdural hematoma with brain herniation carries high mortality and poor neurological outcomes.
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
Hydrogen inhalation plus deep cooling improves the neurologic outcome after cardiac arrest.
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.
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.
2024 · Xie — A novel intervention of molecular hydrogen on the unbalance of the gut microbiome in opioid addiction: Experimental and human studies.
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.
2024 · Ichikawa — Realizing brain therapy with „smart medicine“: mechanism and case report of molecular hydrogen inhalation for Parkinson's disease.
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.
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 · Wang — Effects of molecular hydrogen intervention on the gut microbiome in methamphetamine abusers with mental disorder.
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.
2022 · Benjamin — A potential clinical application of hydrogen-rich saline in patients with traumatic brain injury.
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.
2021 · Hong — Effects of concomitant use of hydrogen water and photobiomodulation on Parkinson disease: A pilot study
H₂ water combined with photobiomodulation lowered Parkinson symptom scores — safely and without side effects.
2018 · Suzuki — Quantification of Hydrogen Production by Intestinal Bacteria That Are Specifically Dysregulated in Parkinson's Disease
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.
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.
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.
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.
2006 · Asaturian et al. — Temporary Clipping and Cerebral Blood Flow in Patients with Cerebral Aneurysms
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.
1993 · Suzuki — Effect of endogenous opioids on gastric functions in man
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.
1988 · Toma et al. — Effect of Endocrine Treatment on Prostatic Blood Flow in Patients with Prostatic Adenocarcinoma
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.
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.
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.
2026 · Zhao — Molecular hydrogen triggers TRPC4-TRPC4AP-dependent reversible calcium transients via extracellular influx
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.
2025 · Chu — Hydrogen Enhanced Photothermal Therapy for Redox-regulated Tumor Apoptosis and Immune Reprogramming
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.
2025 · Li — Hydrogen promoted mitochondrial autophagy and alleviated CIH-induced vascular endothelial cell senescence by regulating oxidative stress.
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.
2025 · Zhang — RNA-Seq Reveals the Mechanism of Synergistic Hydrogen-Chemotherapy Based on Active Magnesium Micromotors for Inhibiting Glioblastoma Recurrence by Modulating Tumor Microenvironment.
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.
2024 · Benoit — d-aspartate, an amino-acid important for human health, supports anaerobic respiration in several Campylobacter species.
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.
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.
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.
2024 · McCurry — Gut bacteria convert glucocorticoids into progestins in the presence of hydrogen gas.
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.
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
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.
2024 · Cui — High-concentration hydrogen inhalation mitigates sepsis-associated encephalopathy in mice by improving mitochondrial dynamics
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.
2023 · Dumbuya — Hydrogen-rich saline regulates NLRP3 inflammasome activation in sepsis-associated encephalopathy rat model
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.
2023 · Iketani — H₂-induced transient upregulation of phospholipids with suppression of energy metabolism
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.
2023 · Sahoo — Hydrogen-producing Photocatalyst at Sunscreen for Athletes in Preventing and Healing Muscle-nerve-skin Injuries
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.
2022 · An — Gender-based differences in neuroprotective effects of hydrogen gas against intracerebral hemorrhage-induced depression
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.
2022 · Liu — In vivo microelectrode monitoring of real-time hydrogen concentration in different tissues of rats after inhaling hydrogen gas
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.
2021 · Yin et al. — Hydrogen Gas with Extracorporeal Cardiopulmonary Resuscitation Improves Survival after Prolonged Cardiac Arrest in Rats
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.
2021 · LeBaron et al. — An H₂-Infused, Nitric Oxide-Producing Functional Beverage as a Neuroprotective Agent for TBIs and Concussions
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.
2021 · Li et al. — Hydrogen-rich water attenuates the radiotoxicity induced by tritium exposure in vitro and in vivo
Hydrogen-rich water (HRW) reduces radioactive damage caused by tritiated water (HTO) — both in cultured human blood cells and in mice.
2021 · Ostojic — Does drinking water rich in hydrogen gas revive brain hypometabolism in neurodegeneration by SCFAs upregulation?
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.
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.
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.
2020 · Zhuang — Molecular hydrogen attenuates sepsis-induced neuroinflammation through regulation of microglia polarization through an mTOR-autophagy-dependent pathway.
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.
2020 · Ishihara — Molecular hydrogen suppresses superoxide generation in the mitochondrial complex I and reduced mitochondrial membrane potential.
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 %.
2020 · Jiao — Protective effects of hydrogen-rich saline against experimental diabetic peripheral neuropathy via activation of the mitochondrial ATP-sensitive potassium channel in rats.
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.
2019 · Chen et al. — Inhaling Hydrogen Ameliorates Early Postresuscitation EEG Characteristics in an Asphyxial Cardiac Arrest Rat Model.
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.
2019 · Bordoni — Positive Effect of an Electrolyzed Reduced Water on Gut Permeability, Fecal Microbiota and Liver in an Animal Model of Parkinson's Disease
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.
2019 · Liu — Molecular Hydrogen Suppresses Glioblastoma Growth via Inducing the Glioma Stem-Like Cell Differentiation
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.
2019 · Htun — Hydrogen ventilation combined with mild hypothermia improves short-term neurological outcomes in a 5-day neonatal hypoxia-ischaemia piglet model.
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.
2019 · Liu — In vitro and in vivo studies of Mg-30Sc alloys with different phase structure for potential usage within bone.
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.
2018 · Yuan — Hydrogen-rich water attenuates oxidative stress in rats with traumatic brain injury via Nrf2 pathway
In a rat model of traumatic brain injury (TBI), hydrogen-rich water significantly improved survival, reduced neurological deficits, and lowered oxidative stress markers.
2018 · Ostojic — Inadequate Production of H₂ by Gut Microbiota and Parkinson Disease
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.
2017 · Murakami — Molecular hydrogen protects against oxidative stress-induced SH-SY5Y neuroblastoma cell death through the process of mitohormesis
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“.
2017 · Biswas — A Comprehensive Computational Study on Pathogenic Missense Mutations Spanning the RING2 and REP Domains of Parkin Protein
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.
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.
2016 · Zhang — Treatment with Hydrogen-Rich Saline Delays Disease Progression in a Mouse Model of Amyotrophic Lateral Sclerosis
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.
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.
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).
2015 · Chikan et al. — Atomic Insight into the Altered O6-Methylguanine-DNA Methyltransferase Protein Architecture in Gastric Cancer.
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.
2014 · Brenner — Parkinson's disease may be due to failure of melanin in the Substantia Nigra to produce molecular hydrogen from dissociation of water.
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.
2014 · Mano et al. — Maternal molecular hydrogen administration ameliorates rat fetal hippocampal damage caused by in utero ischemia-reperfusion.
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.
2012 · Wong et al. — A hydrogen gas-water equilibration method produces accurate and precise stable hydrogen isotope ratio measurements in nutrition studies.
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.
2010 · Qian — The hypothesis of an effective safe and novel radioprotective agent: hydrogen-rich solution.
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.
2010 · Kurisaki — Spontaneous adjustment mechanism in an RNA-binding protein: cooperation between energetic stabilization and target search enhancement.
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.
2010 · Liu — Oral administration of mannitol may be an effective treatment for ischemia-reperfusion injury.
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.
2010 · Liu — Hydrogen therapy may be an effective and specific novel treatment for acute radiation syndrome.
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.
2008 · Song — A role for IOP1 in mammalian cytosolic iron-sulfur protein biogenesis.
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.
2007 · Ohsawa — Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals
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.
1999 · Tamori — Role of calcitonin gene-related peptide and capsaicin-sensitive afferents in central thyrotropin-releasing hormone-induced hepatic hyperemia.
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.
1989 · Heizmann — GasPak Plus versus Anaerocult A — two carbon dioxide/hydrogen systems for cultivation of anaerobes.
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.