Nature Medicine · 2007 · Animal RCT
Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals
Ohsawa et al. · n = animal model
The foundational paper. Ohsawa and colleagues showed that inhaled hydrogen selectively neutralised the most damaging free radicals while leaving beneficial reactive oxygen species intact.
→ Established hydrogen as a selective antioxidant in mammalian models.
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eClinicalMedicine · 2023 · Human RCT
Inhaled hydrogen and neurological outcome after out-of-hospital cardiac arrest (HYBRID II)
Tamura et al., HYBRID II Study Group · n = 73
The first multicentre, randomised, double-blind, placebo-controlled trial of hydrogen inhalation in post-cardiac-arrest care, run across 15 Japanese hospitals. Comatose survivors of out-of-hospital cardiac arrest received 2% hydrogen with oxygen, or oxygen alone, for 18 hours.
→ The primary outcome — good neurological recovery at 90 days — did not reach statistical significance; secondary outcomes favoured hydrogen, with higher 90-day survival (85% vs 61%) and less disability.
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Journal of Thoracic Disease · 2020 · Human trial
Hydrogen/oxygen inhalation in patients with COVID-19
Guan et al. · n = 44
A multicentre Chinese study evaluated hydrogen/oxygen gas mixture inhalation in hospitalised COVID-19 patients, measuring symptom severity and recovery time.
→ Hydrogen/oxygen inhalation was associated with improvement in disease severity scores.
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Movement Disorders · 2013 · Human RCT
Pilot trial of hydrogen-rich water in Parkinson's disease
Yoritaka et al. · n = 18
A randomised, double-blind, placebo-controlled pilot at Juntendo University. Patients on levodopa drank 1,000 ml/day of hydrogen-rich water — not inhaled hydrogen — or placebo water, for 48 weeks.
→ Hydrogen-rich water was associated with improved total Unified Parkinson's Disease Rating Scale scores in this small pilot.
Note: A 2018 follow-up by the same author (Yoritaka A et al., Movement Disorders 33:1505–1507) in a larger sample did not replicate the finding, and a 2021 hydrogen inhalation pilot by the same group also showed no significant effect. This 2013 water study is retained for completeness; it is not inhalation evidence.
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Critical Care Explorations · 2021 · Human safety study
Safety of Prolonged Inhalation of Hydrogen Gas in Air in Healthy Adults
Cole, Sperotto, DiNardo, Carlisle, Rivkin, Sleeper, Kheir · n = 8
Eight healthy adults, prolonged hydrogen inhalation 24–72 hours at 2.4% via high-flow nasal cannula. Endpoints included pulmonary function testing, vital signs, neurological exam, serologic markers. No clinically significant adverse effects.
→ Prolonged hydrogen inhalation was well tolerated with no clinically significant changes in pulmonary function or other safety markers in healthy adults.
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Medical Gas Research · 2025 · Human RCT
Hydrogen inhalation and fat oxidation at rest — randomised crossover trial
Grepl, Botek, Krejčí, McKune · n = 20
20 physically active women, double-blind placebo-controlled crossover, 60 min hydrogen inhalation at 300 ml/min via nasal cannula. Significant RER decrease across all 15-minute intervals; effect correlated with body fat percentage.
→ 60 minutes of hydrogen inhalation was associated with increased fat oxidation at rest.
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Medical Gas Research · 2012 · Human pilot
Open-label trial of hydrogen water in patients with rheumatoid arthritis
Ishibashi et al. · n = 20
Twenty patients with rheumatoid arthritis drank hydrogen-rich water for four weeks, followed by a four-week washout and a second four-week drinking period.
→ Hydrogen water was associated with reductions in disease activity scores and urinary 8-OHdG.
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Circulation Journal · 2017 · Human trial
Effect of inhaled hydrogen on acute myocardial infarction
Katsumata et al. · n = 20
A prospective, open-label, rater-blinded pilot in 20 patients with ST-elevation myocardial infarction, comparing hydrogen inhalation plus oxygen against oxygen alone alongside standard PCI. Left ventricular remodelling was assessed by cardiac MRI.
→ The primary cardiac-salvage measure showed no significant between-group difference; left-ventricular measures at six months favoured the hydrogen group numerically.
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Journal of Stroke and Cerebrovascular Diseases · 2017 · Human RCT
Hydrogen inhalation therapy in acute ischaemic stroke patients
Ono et al. · n = 50
A Japanese single-centre trial evaluated hydrogen gas inhalation alongside standard stroke care, measuring NIHSS scores and functional recovery at 90 days.
→ Hydrogen inhalation was associated with improved NIHSS scores at discharge.
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Journal of Lipid Research · 2013 · Human pilot
Hydrogen-rich water and lipid metabolism in patients with metabolic syndrome
Song et al. · n = 20
An open-label 10-week pilot study measured serum LDL cholesterol, HDL function and urinary oxidative stress markers in patients with metabolic syndrome.
→ Hydrogen water was associated with reduced LDL cholesterol and improved HDL function.
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QJM: An International Journal of Medicine · 2020 · Prospective study
Hydrogen gas (XEN) inhalation ameliorates airway inflammation in asthma and COPD patients
Wang S-T, Bao C, He Y, Tian X, Yang Y, Zhang T, Xu K-F · n = 20 (10 asthma, 10 COPD)
Single 45-minute hydrogen inhalation session reduced airway inflammatory mediators in human subjects with asthma or COPD. Mechanism-relevant data for the selective antioxidant effect in respiratory tissue.
→ Single 45-min inhalation reduced MCP-1 levels in both COPD and asthma groups; reduced IL-8 in asthma group.
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Medical Gas Research · 2020 · Human clinical trial
Hydrogen inhalation during post-exercise recovery — oxidative stress and muscle damage
Shibayama et al. · n = 8 (healthy men)
Eight physically active men inhaled a hydrogen-rich gas mixture through a nasal cannula during a 60-minute recovery period after strenuous exercise, in a double-blind placebo-controlled crossover. Oxidative-stress and muscle-damage markers and subsequent performance were measured.
→ Hydrogen inhalation during recovery was associated with an attenuated decline in subsequent jump performance; effects on oxidative-stress markers were mixed.
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Frontiers in Pharmacology · 2022 · Human RCT
Low-dose hydrogen-oxygen inhalation in adults with hypertension
Liu et al. · n = 60 (56 completed)
A randomised, placebo-controlled trial in adults aged 50–70 with hypertension. Participants inhaled a low-dose hydrogen-oxygen mixture, or placebo air, four hours a day for two weeks, with four-limb and 24-hour ambulatory blood pressure monitored throughout.
→ Systolic blood pressure fell significantly from baseline in the hydrogen-oxygen group, with a reduction in night-time diastolic ambulatory pressure; placebo was unchanged.
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Medical Gas Research · 2011 · Human RCT
Hydrogen-rich water and quality of life in cancer patients undergoing radiotherapy
Kang et al. · n = 49
A randomised placebo-controlled trial measured quality-of-life scores and side-effect severity in patients receiving radiotherapy for liver cancer.
→ Hydrogen water drinkers reported better quality-of-life scores during radiotherapy.
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Diabetes, Metabolic Syndrome and Obesity · 2020 · Human RCT
Hydrogen-rich water and body composition in overweight adults
LeBaron et al. · n = 60
A 24-week randomised trial measured changes in body fat percentage, waist circumference and metabolic markers in adults with elevated BMI.
→ Hydrogen-rich water was associated with reduced cholesterol, glucose and HbA1c; the change in body-fat measures was a non-significant trend.
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Current Alzheimer Research · 2018 · Human RCT
Molecular hydrogen and mild cognitive impairment — a randomised clinical study
Nishimaki, Asada, Ohsawa et al. · n = 73
A 12-month randomised, double-blind, placebo-controlled trial. Adults with mild cognitive impairment received either hydrogen-rich water or placebo water daily. ADAS-cog was the primary cognitive outcome.
→ Hydrogen water significantly improved ADAS-cog scores in the APOE4-genotype subgroup — the cohort most genetically vulnerable to brain oxidative stress.
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Medical Gas Research · 2017 · Human trial
Hydrogen-rich water and mood, anxiety, and autonomic nerve function in daily life
Mizuno, Sasaki, Ebisu et al.
Healthy adults — not patients — drank hydrogen-rich water daily across a four-week intervention. Mood inventories, anxiety scores, and autonomic nervous function were measured.
→ Hydrogen water was associated with improvements in subjective mood and objective autonomic nervous balance in healthy adults.
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Scientific Reports · 2020 · Human RCT
Hydrogen-rich water and inflammatory responses in healthy adults — a randomised controlled trial
Sim, Kim, Shon et al. · n = 38
A 4-week double-blind controlled trial in healthy adults aged 20-59. Hydrogen-rich water consumed at 1.5 L daily. Outcomes measured at the transcriptomic level — gene expression networks, immune cell apoptosis, antioxidant potential.
→ Pro-inflammatory signalling pathways (TLR, NF-κB) showed reduced transcription; immune cell apoptosis was significantly lower in the hydrogen group.
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International Immunopharmacology · 2014 · Human RCT
Infused molecular hydrogen in saline for rheumatoid arthritis — a randomised double-blind placebo-controlled pilot
Ishibashi, Sato, Shibata et al. · n = 24
A clinical pilot trial at Haradoi Hospital following the 2012 open-label signal. Patients with rheumatoid arthritis received hydrogen-infused saline or placebo. Disease activity scores were the primary endpoint.
→ Hydrogen-infused saline was associated with measurable reductions in disease activity compared with placebo.
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Biology of Sport · 2019 · Human RCT
Short-term H2 inhalation improves running performance and torso strength in healthy adults
Javorac et al. · n = 20
A 7-day double-blind placebo-controlled crossover. Participants inhaled either 4% hydrogen or room air for 20 minutes a day, with a washout period between conditions.
→ Peak running velocity in an incremental maximal test rose by up to 4.2% on hydrogen versus placebo; authors framed the molecule as showing “ergogenic properties”.
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Medical Gas Research · 2012 · Human pilot
Hydrogen-rich water and muscle fatigue caused by acute exercise in elite athletes — a pilot study
Aoki et al. · n = 10 (elite soccer players)
Double-blind crossover pilot. Hydrogen-rich water consumed before heavy exercise; blood lactate and muscle function were measured during and after the bout.
→ Hydrogen-rich water prevented the usual rise in blood lactate and reduced the early decline in muscle function versus placebo.
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Frontiers in Physiology · 2024 · Human RCT
Hydrogen-rich water and muscle recovery between two same-day training sessions in elite fin swimmers
Sládečková et al. · elite fin swimmers
Double-blind placebo-controlled crossover. Elite fin swimmers completed two strenuous training sessions on the same day with hydrogen-rich water or placebo; recovery markers were measured at 24 hours.
→ The hydrogen group showed measurably better muscle recovery markers at the 24-hour mark.
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Journal of Clinical Medicine Research · 2020 · Pharmacokinetic
Low-flow nasal cannula hydrogen therapy
Sano et al. · n = animal model
Pharmacokinetic study using three micro miniature pigs. Pure hydrogen inhaled through a standard nasal cannula at a low flow rate of 250 ml/min; arterial blood hydrogen concentrations were measured.
→ A low-flow nasal cannula delivered arterial blood hydrogen at concentrations the wider literature considers therapeutically active.
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Vascular Health and Risk Management · 2014 · Human RCT
Consumption of water containing over 3.5 mg of dissolved hydrogen could improve vascular endothelial function
Sakai, Sato, Hara et al. · n = 34 (healthy adults)
Placebo-controlled trial. Healthy adults consumed water with dissolved molecular hydrogen; flow-mediated dilation — the standard non-invasive test of endothelial responsiveness — was measured before and after.
→ Flow-mediated dilation rose in the high-hydrogen group and fell in the placebo group; endothelial responsiveness improved measurably.
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PLOS One · 2020 · Human RCT
Peripheral endothelial function can be improved by daily consumption of water containing over 7 ppm of dissolved hydrogen
Ishibashi, Kawamoto, Matsuno et al. · n = 68
A 14-day placebo-controlled trial in healthy adults. Peripheral endothelial function was measured by reactive hyperemia index — a finer-grained smaller-vessel response test.
→ The hydrogen group showed improved reactive hyperemia scores; authors concluded that continuous consumption of high-H2 water contributes to improved cardiovascular health.
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Nutrition Research · 2008 · Human RCT
Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes mellitus or impaired glucose tolerance
Kajiyama, Hasegawa, Asano et al. · n = 30
An 8-week double-blind placebo-controlled crossover trial. Adults with impaired glucose tolerance or diabetes consumed 900 ml/day of hydrogen-rich water or placebo. Lipid markers and glucose metabolism markers were measured.
→ Hydrogen-rich water was associated with reductions in oxidised LDL and improvements in lipoprotein metabolism markers.
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Journal of Clinical Biochemistry and Nutrition · 2010 · Human pilot
Effectiveness of hydrogen-rich water on antioxidant status of subjects with potential metabolic syndrome
Nakao, Toyoda, Sharma et al. · n = 20
A 10-week open-label trial in adults with features of metabolic syndrome. Participants consumed 1.5–2.0 L/day of hydrogen-rich water. Urinary thiobarbituric acid reactive substances, antioxidant enzyme activity and serum lipid markers were measured.
→ Hydrogen-rich water was associated with improved antioxidant enzyme activity and favourable changes in lipid metabolism markers.
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Scientific Reports · 2019 · Animal pharmacokinetic
Hydrogen gas distribution in organs after inhalation — real-time monitoring of tissue hydrogen concentration in rat
Yamamoto, Homma, Suzuki, Sano, Sasaki · n = animal model
Real-time tissue hydrogen monitoring during and after inhalation in rats. Hydrogen concentrations were measured directly in liver, kidney, mesentery fat, skeletal muscle and brain.
→ Inhaled hydrogen reached liver, kidney, mesentery fat and skeletal muscle in measurable concentrations within minutes.
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Antioxidants (Basel) · 2023 · Human RCT
Hydrogen-rich water ameliorates metabolic disorder via modifying gut microbiota in impaired fasting glucose patients — a randomised controlled study
Liang, Shi, Du et al. · n = 73
Seventy-three IFG patients, double-blind placebo-controlled, 8 weeks of 1000 ml/day hydrogen-rich water. Modest improvements in metabolic parameters with concurrent shifts in gut microbiota composition.
→ Hydrogen-rich water was associated with modest improvements in metabolic parameters and favourable shifts in gut microbiota composition.
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Pharmacology & Therapeutics · 2014 · Review
Molecular hydrogen as a preventive and therapeutic medical gas: initiation, development and potential of hydrogen medicine
Ohta S · narrative review
Seven-year mechanism review by the lab that proposed the selective-antioxidant hypothesis. Tracks how the field developed from the 2007 founding paper through 2014 across more than 38 diseases, physiological states and clinical tests.
→ Mechanism held up under scrutiny; signalling modulation, anti-inflammatory effects and Nrf2 engagement added to the picture.
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Medical Gas Research · 2015 · Review
Beneficial biological effects and the underlying mechanisms of molecular hydrogen — comprehensive review of 321 original articles
Ichihara, Sobue, Ito et al. · review of 321 articles
Comprehensive accounting of 321 original research articles on H2’s biological effects published between 2007 and mid-2015. Establishes the breadth of the field across neurological, cardiovascular, metabolic, inflammatory and respiratory systems.
→ Established the breadth of hydrogen's biological activity across physiological systems through the field's first decade.
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Cell · 2013 · Review
The Hallmarks of Aging
López-Otín, Blasco, Partridge, Serrano, Kroemer · framework review
Not a hydrogen study, but the framework on which serious ageing research now sits. Five authors set out nine cellular hallmarks of ageing — including mitochondrial dysfunction and the oxidative stress that accompanies it — that have become the standard map of what changes as cells age. Among the most cited papers in biology.
→ Established the dominant cellular framework for studying ageing — including the mitochondrial and oxidative-stress pathways hydrogen research addresses.
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Biochimica et Biophysica Acta · 2012 · Review
Molecular hydrogen is a novel antioxidant to efficiently reduce oxidative stress with potential for the improvement of mitochondrial diseases
Ohta S · narrative review
A focused review of hydrogen at the mitochondrial level by the head of the lab that proposed the selective-antioxidant hypothesis. Argues that mitochondria are the major source of cellular oxidative stress and that persistent oxidative stress is one of the factors involved in the ageing process.
→ Connected the selective-antioxidant mechanism directly to mitochondrial dysfunction and the biology of cellular ageing.
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Scientific Reports · 2016 · Cell study
Molecular hydrogen regulates gene expression by modifying the free radical chain reaction-dependent generation of oxidized phospholipid mediators
Iuchi, Imoto, Kamimura et al. · cell-based study
From the same lab as the 2007 founding paper. Showed that hydrogen can influence gene expression — not by acting on DNA directly, but by modifying the chain of oxidised-lipid signals that cells use to regulate their own activity.
→ Demonstrated that hydrogen acts on the cell's regulatory machinery, not only as a radical scavenger.
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Medical Gas Research · 2026 · Human RCT
Hydrogen-oxygen inhalation, sleep quality and mood
Gao et al. · n = 66
A single-blind, randomised controlled trial in 66 adults with sleep disorders across two Chinese hospitals. Participants received seven days of nasal hydrogen-oxygen inhalation or standard care, with sleep tracked objectively by actigraphy alongside the Pittsburgh Sleep Quality Index and mood scales.
→ The hydrogen-oxygen group showed greater total sleep time and sleep efficiency and less wake time, with lower PSQI scores (indicating better sleep quality) and lower depression scores; anxiety scores did not differ significantly. Early evidence from a small, two-site trial that may support better sleep.
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