Molecular hydrogen therapy in Parkinson’s disease: a pilot studyScientific Research

Pilot study of H2 therapy in Parkinson’s disease: A randomized double-blind placebo-controlled trial



Oxidative stress is associated with the progression of Parkinson’s disease (PD). Recent studies have confirmed that molecular hydrogen (H2) is a potent antioxidant in cultured cells and animal models. Drinking H2-dissolved water (H2-water) reduces oxidative stress and improves Parkinson’s disease characteristics in model animals.


In this pilot, placebo-controlled, randomized, double-blind, parallel-group clinical study, the authors evaluated the efficacy of H2 water in Japanese patients with Parkinson’s disease treated with levodopa. Participants drank 1,000 ml of H2 water or mock water daily for 48 weeks.


The President-Parkinson’s Disease Rating Scale (UPDRS) score improved in the H2 water group (n=9) (median, -1.0; mean ± SD, -5.7 ± 8.4) compared to the UPDRS score in the placebo group Worsening (n = 8) (median 4.5; mean ± SD 4.1 ± 9.2). Despite the smallest number of patients and short study duration, the difference was significant (P < 0.05).


The results showed that drinking H2 water was safe and well tolerated, and patients in the H2 water group had a significant improvement in their overall UPDRS score. © 2013 Movement Disorders Association


  • Molecular hydrogen as a nutraceutical for extending the health span, Functional Foods and Nutraceuticals in Metabolic and Non-Communicable Diseases, 10.1016/B978-0-12-819815-5.00019-7, (757-770), (2022).
  • Hydrogen water as a treatment for myalgic encephalomyelitis/chronic fatigue syndrome: a pilot randomized trial, Fatigue: Biomedicine, Health & Behavior, 10.1080/21641846.2022.203851910, 1, (26-39), (2022).
  • Role of Molecular Hydrogen in Ageing and Ageing-Related Diseases, Oxidative Medicine and Cellular Longevity, 10.1155/2022/22497492022, (1-17), (2022).
  • Different effects of hydrogen-rich water intake and hydrogen gas inhalation on gut microbiome and plasma metabolites of rats in health status, Scientific Reports, 10.1038/s41598-022-11091-112, 1, (2022).
  • An Activity‐Based Ratiometric Fluorescent Probe for In Vivo Real‐Time Imaging of Hydrogen Molecules, Angewandte Chemie International Edition, 10.1002/anie.20211459461, 9, (2022).
  • An Activity‐Based Ratiometric Fluorescent Probe for In Vivo Real‐Time Imaging of Hydrogen Molecules, Angewandte Chemie, 10.1002/ange.202114594134, 9, (2022).
  • Implications of Gut Microbiota in Neurodegenerative Diseases, Frontiers in Immunology, 10.3389/fimmu.2022.78564413, (2022).
  • Molecular Hydrogen Enhances Proliferation of Cancer Cells That Exhibit Potent Mitochondrial Unfolded Protein Response, International Journal of Molecular Sciences, 10.3390/ijms2305288823, 5, (2888), (2022).
  • Molecular Hydrogen as a Medical Gas for the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Possible Efficacy Based on a Literature Review, Frontiers in Neurology, 10.3389/fneur.2022.84131013, (2022).
  • Effects of concomitant use of hydrogen water and photobiomodulation on Parkinson disease, Medicine, 10.1097/MD.0000000000024191100, 4, (e24191), (2021).
  • Peritoneal lavage with hydrogen-rich saline can be an effective and practical procedure for acute peritonitis, Surgery Today, 10.1007/s00595-021-02271-z51, 11, (1860-1871), (2021).
  • Hydrogen-saturated saline mediated neuroprotection through autophagy via PI3K/AKT/mTOR pathway in early and medium stages of rotenone-induced Parkinson’s disease rats, Brain Research Bulletin, 10.1016/j.brainresbull.2021.04.003172, (1-13), (2021).
  • Hydrogen‐rich water and caffeine for alertness and brain metabolism in sleep‐deprived habitual coffee drinkers, Food Science & Nutrition, 10.1002/fsn3.24809, 9, (5139-5145), (2021).
  • Biological Responses to Hydrogen Molecule and its Preventive Effects on Inflammatory Diseases, Current Pharmaceutical Design, 10.2174/138161282666620092512351027, 5, (659-666), (2021).
  • Protective Effects of Hydrogen against Irradiation, Current Pharmaceutical Design, 10.2174/138161282766621011910354527, 5, (679-686), (2021).
  • Hydrogen medicine: A rising star in gas medicine, Traditional Medicine and Modern Medicine, 10.1142/S257590002030005203, 03, (153-161), (2021).
  • Potential Therapeutic Applications of Hydrogen in Chronic Inflammatory Diseases: Possible Inhibiting Role on Mitochondrial Stress, International Journal of Molecular Sciences, 10.3390/ijms2205254922, 5, (2549), (2021).
  • Molecular Hydrogen as a Potential Clinically Applicable Radioprotective Agent, International Journal of Molecular Sciences, 10.3390/ijms2209456622, 9, (4566), (2021).
  • Molecular Hydrogen as a Novel Antitumor Agent: Possible Mechanisms Underlying Gene Expression, International Journal of Molecular Sciences, 10.3390/ijms2216872422, 16, (8724), (2021).
  • Prenatal Molecular Hydrogen Administration Ameliorates Several Findings in Nitrofen-Induced Congenital Diaphragmatic Hernia, International Journal of Molecular Sciences, 10.3390/ijms2217950022, 17, (9500), (2021).
  • Molecular Hydrogen: A Promising Adjunctive Strategy for the Treatment of the COVID-19, Frontiers in Medicine, 10.3389/fmed.2021.6712158, (2021).
  • Small Intestinal Bacterial Overgrowth as Potential Therapeutic Target in Parkinson’s Disease, International Journal of Molecular Sciences, 10.3390/ijms22211166322, 21, (11663), (2021).
  • Molecular Hydrogen as Medicine: An Assessment of Administration Methods, Hydrogen, 10.3390/hydrogen20400252, 4, (444-460), (2021).
  • Therapeutic Effects of Hydrogen Gas Inhalation on Trimethyltin-Induced Neurotoxicity and Cognitive Impairment in the C57BL/6 Mice Model, International Journal of Molecular Sciences, 10.3390/ijms22241331322, 24, (13313), (2021).
  • Hydrogen and therapeutic gases for neonatal hypoxic–ischemic encephalopathy: potential neuroprotective adjuncts in translational research, Pediatric Research, 10.1038/s41390-020-0998-z89, 4, (753-759), (2020).
  • Does drinking water rich in hydrogen gas revive brain hypometabolism in neurodegeneration by SCFAs upregulation?, European Journal of Clinical Nutrition, 10.1038/s41430-020-0680-x75, 1, (212-213), (2020).
  • Neuroprotective Effects of Molecular Hydrogen: A Critical Review, Neuroscience Bulletin, 10.1007/s12264-020-00597-137, 3, (389-404), (2020).
  • Si Nanopowder for Photoluminescence and Hydrogen Generation Materials, Theoretical Chemistry for Advanced Nanomaterials, 10.1007/978-981-15-0006-0, (353-382), (2020).
  • Hydrogen Attenuates Allergic Inflammation by Reversing Energy Metabolic Pathway Switch, Scientific Reports, 10.1038/s41598-020-58999-010, 1, (2020).
  • Renoprotective and neuroprotective effects of enteric hydrogen generation from Si-based agent, Scientific Reports, 10.1038/s41598-020-62755-910, 1, (2020).
  • Hydrogen gas represses the progression of lung cancer via down-regulating CD47, Bioscience Reports, 10.1042/BSR2019276140, 4, (2020).
  • Dependencies of hydrogen-water on mineral-based hardness, temperatures and the container materials, and effects of the oral washing and drinking, Medical Gas Research, 10.4103/2045-9912.28555910, 2, (67), (2020).
  • Hydrogen vs. Caffeine for Improved Alertness in Sleep-Deprived Humans, Neurophysiology, 10.1007/s11062-020-09852-752, 1, (67-72), (2020).
  • Prospects of molecular hydrogen in perioperative neuroprotection from basic research to clinical application, Current Opinion in Anaesthesiology, 10.1097/ACO.000000000000091533, 5, (655-660), (2020).
  • Hydrogen: A Novel Option in Human Disease Treatment, Oxidative Medicine and Cellular Longevity, 10.1155/2020/83847422020, (1-17), (2020).
  • Development of Molecular Hydrogen Medicine, Molecular Hydrogen for Medicine, 10.1007/978-981-15-7157-2, (13-60), (2020).
  • Hydrogen: An Endogenous Regulator of Liver Homeostasis, Frontiers in Pharmacology, 10.3389/fphar.2020.0087711, (2020).
  • Hydrogen Is Promising for Medical Applications, Clean Technologies, 10.3390/cleantechnol20400332, 4, (529-541), (2020).
  • Molecular and Cellular Mechanisms Associated with Effects of Molecular Hydrogen in Cardiovascular and Central Nervous Systems, Antioxidants, 10.3390/antiox91212819, 12, (1281), (2020).
  • Molecular hydrogen attenuates gefitinib-induced exacerbation of naphthalene-evoked acute lung injury through a reduction in oxidative stress and inflammation, Laboratory Investigation, 10.1038/s41374-019-0187-z99, 6, (793-806), (2019).
  • Hydrogen gas inhalation enhances alveolar macrophage phagocytosis in an ovalbumin-induced asthma model, International Immunopharmacology, 10.1016/j.intimp.2019.05.03174, (105646), (2019).
  • Hydrogen-producing milk to prevent reduction in tear stability in persons using visual display terminals, The Ocular Surface, 10.1016/j.jtos.2019.07.008, (2019).
  • Therapeutic Efficacy of Molecular Hydrogen: A New Mechanistic Insight, Current Pharmaceutical Design, 10.2174/138161282566619050612303825, 9, (946-955), (2019).
  • Myalgic encephalomyelitis/chronic fatigue syndrome: From pathophysiological insights to novel therapeutic opportunities, Pharmacological Research, 10.1016/j.phrs.2019.104450148, (104450), (2019).
  • Faecal Transplantation, Pro- and Prebiotics in Parkinson’s Disease; Hope or Hype?, Journal of Parkinson’s Disease, 10.3233/JPD-191802, (1-9), (2019).
  • Micro/Nanomaterials‐Augmented Hydrogen Therapy, Advanced Healthcare Materials, 10.1002/adhm.2019004638, 16, (2019).
  • Hydrogen gas: from clinical medicine to an emerging ergogenic molecule for sports athletes, Canadian Journal of Physiology and Pharmacology, 10.1139/cjpp-2019-0067, (1-11), (2019).
  • Gut Microbiota in Neurological Disorders, Archivum Immunologiae et Therapiae Experimentalis, 10.1007/s00005-019-00561-6, (2019).
  • Prevention of ischemia-induced hearing loss by intravenous administration of hydrogen-rich saline in gerbil, Neuroscience Letters, 10.1016/j.neulet.2017.12.013665, (195-199), (2018).
  • Molecular hydrogen reduces acute exercise-induced inflammatory and oxidative stress status, Free Radical Biology and Medicine, 10.1016/j.freeradbiomed.2018.09.028129, (186-193), (2018).
  • Local generation of hydrogen for enhanced photothermal therapy, Nature Communications, 10.1038/s41467-018-06630-29, 1, (2018).
  • Effects of alkaline-electrolyzed and hydrogen-rich water, in a high-fat-diet nonalcoholic fatty liver disease mouse model, World Journal of Gastroenterology, 10.3748/wjg.v24.i45.509524, 45, (5095-5108), (2018).
  • Clinical Applications of Magnesium Hydride, Magnesium Alloys – Selected Issue, 10.5772/intechopen.74194, (2018).
  • Administration of molecular hydrogen during pregnancy improves behavioral abnormalities of offspring in a maternal immune activation model, Scientific Reports, 10.1038/s41598-018-27626-48, 1, (2018).
  • Inadequate Production of H2 by Gut Microbiota and Parkinson Disease, Trends in Endocrinology & Metabolism, 10.1016/j.tem.2018.02.00629, 5, (286-288), (2018).
  • Molecular hydrogen upregulates heat shock response and collagen biosynthesis, and downregulates cell cycles: meta-analyses of gene expression profiles, Free Radical Research, 10.1080/10715762.2018.143916652, 4, (434-445), (2018).
  • Randomized, double‐blind, multicenter trial of hydrogen water for Parkinson’s disease, Movement Disorders, 10.1002/mds.2747233, 9, (1505-1507), (2018).
  • Quantification of hydrogen production by intestinal bacteria that are specifically dysregulated in Parkinson’s disease, PLOS ONE, 10.1371/journal.pone.020831313, 12, (e0208313), (2018).
  • Effect of molecular hydrogen on coenzyme Q in plasma, myocardial tissue and mitochondria of rats, Journal of Nutritional Health & Food Engineering, 10.15406/jnhfe.2018.08.002968, 5, (2018).
  • Changes of Colonic Bacterial Composition in Parkinson’s Disease and Other Neurodegenerative Diseases, Nutrients, 10.3390/nu1006070810, 6, (708), (2018).
  • Hydrogen-Rich Water Ameliorates Autistic-Like Behavioral Abnormalities in Valproic Acid-Treated Adolescent Mice Offspring, Frontiers in Behavioral Neuroscience, 10.3389/fnbeh.2018.0017012, (2018).
  • Hydrogen alleviates hyperoxic acute lung injury related endoplasmic reticulum stress in rats through upregulation of SIRT1, Free Radical Research, 10.1080/10715762.2017.135102751, 6, (622-632), (2017).
  • Hydrogen generation by reaction of Si nanopowder with neutral water, Journal of Nanoparticle Research, 10.1007/s11051-017-3873-z19, 5, (2017).
  • Molecular hydrogen in the treatment of acute and chronic neurological conditions: mechanisms of protection and routes of administration, Journal of Clinical Biochemistry and Nutrition, 10.3164/jcbn.16-8761, 1, (1-5), (2017).
  • Molecular hydrogen: a preventive and therapeutic medical gas for various diseases, Oncotarget, 10.18632/oncotarget.211308, 60, (102653-102673), (2017).
  • Molecular hydrogen alleviates motor deficits and muscle degeneration in mdx mice , Redox Report, 10.1080/13510002.2015.113558022, 1, (26-34), (2016).
  • Is melanin a source of bioactive molecular hydrogen?, Pharmacological Research, 10.1016/j.phrs.2015.12.002103, (177-179), (2016).
  • Clinical Effects of Hydrogen Administration: From Animal and Human Diseases to Exercise Medicine, International Journal of Clinical Medicine, 10.4236/ijcm.2016.7100507, 01, (32-76), (2016).
  • Molecular hydrogen stimulates the gene expression of transcriptional coactivator PGC-1α to enhance fatty acid metabolism, npj Aging and Mechanisms of Disease, 10.1038/npjamd.2016.82, 1, (2016).
  • Preventive Effect of Hydrogen Water on the Development of Detrusor Overactivity in a Rat Model of Bladder Outlet Obstruction, The Journal of Urology, 10.1016/j.juro.2015.10.117195, 3, (780-787), (2016).
  • Molecular Hydrogen Alleviates Cellular Senescence in Endothelial Cells, Circulation Journal, 10.1253/circj.CJ-16-022780, 9, (2037-2046), (2016).
  • A randomized double-blind multi-center trial of hydrogen water for Parkinson’s disease: protocol and baseline characteristics, BMC Neurology, 10.1186/s12883-016-0589-016, 1, (2016).
  • Should hydrogen therapy be included in a musculoskeletal medicine routine?, F1000Research, 10.12688/f1000research.9758.15, (2659), (2016).
  • Preventive and Therapeutic Application of Molecular Hydrogen in Situations With Excessive Production of Free Radicals, Physiological Research, 10.33549/physiolres.933414, (S11-S28), (2016).
  • Molecular hydrogen regulates gene expression by modifying the free radical chain reaction-dependent generation of oxidized phospholipid mediators, Scientific Reports, 10.1038/srep189716, 1, (2016).
  • Hydrogen-Rich Saline Attenuated Subarachnoid Hemorrhage-Induced Early Brain Injury in Rats by Suppressing Inflammatory Response: Possible Involvement of NF-κB Pathway and NLRP3 Inflammasome, Molecular Neurobiology, 10.1007/s12035-015-9242-y53, 5, (3462-3476), (2015).
  • Molecular Hydrogen as a Novel Antioxidant, Hydrogen Sulfide in Redox Biology, Part B, 10.1016/bs.mie.2014.11.038, (289-317), (2015).
  • Targeting molecular hydrogen to mitochondria: Barriers and gateways, Pharmacological Research, 10.1016/j.phrs.2015.02.00494, (51-53), (2015).
  • Molecular hydrogen: An inert gas turns clinically effective, Annals of Medicine, 10.3109/07853890.2015.103476547, 4, (301-304), (2015).
  • Potential ghrelin-mediated benefits and risks of hydrogen water, Medical Hypotheses, 10.1016/j.mehy.2015.01.01884, 4, (350-355), (2015).
  • Protective effect of molecular hydrogen against white matter ischemic injury, Cerebral Blood Flow and Metabolism (Japanese journal of cerebral blood flow and metabolism), 10.16977/cbfm.26.2_7726, 2, (77-81), (2015).
  • Beneficial biological effects and the underlying mechanisms of molecular hydrogen – comprehensive review of 321 original articles –, Medical Gas Research, 10.1186/s13618-015-0035-15, 1, (2015).
  • Convenient methods for ingestion of molecular hydrogen: drinking, injection, and inhalation, Medical Gas Research, 10.1186/s13618-015-0034-25, 1, (2015).
  • Therapeutic Effects of Hydrogen on Different Diseases, Hydrogen Molecular Biology and Medicine, 10.1007/978-94-017-9691-0, (81-97), (2015).
  • Effectiveness of Oral and Topical Hydrogen for Sports-Related Soft Tissue Injuries, Postgraduate Medicine, 10.3810/pgm.2014.09.2813126, 5, (188-196), (2015).
  • Intestinal Dysbiosis and Lowered Serum Lipopolysaccharide-Binding Protein in Parkinson’s Disease, PLOS ONE, 10.1371/journal.pone.014216410, 11, (e0142164), (2015).
  • Effects of hydrogen-rich water on aging periodontal tissues in rats, Scientific Reports, 10.1038/srep055344, 1, (2014).
  • Molecular hydrogen as a preventive and therapeutic medical gas: initiation, development and potential of hydrogen medicine, Pharmacology & Therapeutics, 10.1016/j.pharmthera.2014.04.006144, 1, (1-11), (2014).
  • Oral ‘hydrogen water’ induces neuroprotective ghrelin secretion in mice, Scientific Reports, 10.1038/srep032733, 1, (2013).

Leave a Reply