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Molecular Hydrogen Research

In just 13 years of molecular hydrogen research, there have been over 2,000 published scientific articles on the health benefits of various methods of hydrogen consumption. Publications on human trials using hydrogen as a therapeutic agent are approaching 100. Hydrogen therapy has been shown to benefit every organ in the mammalian body in over 170 trials.

As of our last update on molecular hydrogen research, there are 86 publications on hydrogen therapy in humans. The majority, 51, cover drinking hydrogen water. Hydrogen inhalation is a distant second with 15 publications, hydrogen-rich saline is third with 11 publications, and topical hydrogen therapy has nine publications, eight of them on hydrogen water bathing. Finally, three publications cover a product used to create hydrogen gas inside the body, two by hydrogen tablets, and one by the drug acarbose. This totals 89 administration methods because in two of the publications more than one delivery method of hydrogen therapy was used.

Of the 86 human trials, four did not find a benefit. But 82 did, which is a 95% success rate of using hydrogen therapy. Of note, none of the molecular hydrogen research trials that have found a benefit are phase III–type multicenter trials, although many are randomized, double-blind, placebo-controlled phase I– and phase II–type trials. As such, no firm conclusions can be made on the efficacy of hydrogen therapy for any of these indications. Also of note, precise dosing and delivery method, as well as the timing of consumption, are not yet established for any indication, and the literature varies widely in this regard.

This molecular hydrogen research database compiles the ongoing human research on hydrogen therapy for researchers and consumers alike and is not intended to be used to diagnose, treat, or cure any disease.

HUMAN RESEARCH ON HYDROGEN THERAPY

Metabolic and Mitochondrial Athletic Performance, Recovery, and Athlete Health Brain Recovery from Acute Injury, Neurological Conditions, and Brain Health Skin Rheumatoid Arthritis Dialysis Chemo & Radiation Side Effect Reduction Cancer Antioxidant Other Electrically Reduced Water and Magnesium-Based Ingestible Interventions for “-ORP” Magnesium Implants A Sampling of the Many Review Articles

Metabolic and Mitochondrial

There are currently 12 publications on human trials for hydrogen therapy and various metabolic outcomes. Hydrogen water is the most common mode of delivery, with hydrogen water research accounting for nine of the 12 publications. Two publications discuss ways to produce molecular hydrogen within the body, and one discusses hydrogen inhalation.

1. Diabetes Type 2, hydrogen water

Kajiyama et al., 2008. Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. Nutrition Research.

2. Metabolic syndrome, hydrogen water

Nakao et al., 2010. Effectiveness of Hydrogen Rich Water on Antioxidant Status of Subjects with Potential Metabolic Syndrome—An Open Label Pilot Study. Journal of Clinical Biochemistry and Nutrition.

3. Metabolic syndrome, hydrogen water

Song et al., 2013. Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome. Journal of Lipid Research.

4. High cholesterol, hydrogen water

Song et al., 2015. Hydrogen Activates ATP-Binding Cassette Transporter A1-Dependent Efflux Ex Vivo and Improves High-Density Lipoprotein Function in Patients with Hypercholesterolemia: A Double-Blinded, Randomized, and Placebo-Controlled Trial. The Journal of Clinical Endocrinology & Metabolism.

5. Mitochondrial and inflammatory myopathies, hydrogen water

Ito et al., 2011. Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies. Medical Gas Research.

6. Body comp/metabolism, oral H₂ tablets

Korovljev et al., 2018. Molecular hydrogen affects body composition, metabolic profiles, and mitochondrial function in middle-aged overweight women. Irish Journal of Medical Science.

7. Non-Alcoholic Fatty Liver Disease (NAFLD), hydrogen water OUR HYDROGEN TABLETS

Korovljev et al., 2019. 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. Clinics and Research in Hepatology and Gastroenterology.

8. Secondary analysis on NAFLD via HOMA2-insulin sensitivity, hydrogen water OUR HYDROGEN TABLETS

Korovljev et al., 2019. Hydrogen-Rich Water Positively Affects HOMA2 Variables in Physically Inactive Population. Abstract from the 5th International Scientific Conference on Exercise and Quality of Life. PAGE 3

9. Vascular endothelial function, hydrogen water, high acute dose

Sakai et al., 2014. Consumption of Water Containing Over 3.5 Mg of Dissolved Hydrogen Could Improve Vascular Endothelial Function. Vascular Health and Risk Management.

10. Cardiometabolic risk factors in elderly, hydrogen inhalation

Korovljev et al., 2018. Hydrogen Inhalation Positively Affects Cardiometabolic Risk Factors in Men and Women Aged 65 Years or Older: A Preliminary Report. European Geriatric Medicine.

11. Reduction in IL-1b mRNA in peripheral blood in type 2 diabetics post meal, acarbose for internal H₂ production*

Tamasawa et al, 2015. Hydrogen Gas Production Is Associated With Reduced Interleukin-1β Mrna in Peripheral Blood After a Single Dose of Acarbose in Japanese Type 2 Diabetic Patients. European Journal of Pharmacology.

12. Body composition, blood lipid profiles and inflammation biomarkers in men and women with metabolic syndrome, hydrogen water OUR HYDROGEN TABLETS

LeBaron TW, Singh RB, Fatima G, Kartikey K, Sharma JP, Ostojic SM, Gvozdjakova A, Kura B, Noda M, Mojto V, Niaz MA, Slezak J. The Effects of 24-Week, High-Concentration Hydrogen-Rich Water on Body Composition, Blood Lipid Profiles and Inflammation Biomarkers in Men and Women With Metabolic Syndrome: A Randomized Controlled Trial. Diabetes Metab Syndr Obes. 2020;13:889-896 https://doi.org/10.2147/DMSO.S240122

13. Peripheral endothelial function, hydrogen water

Ishibashi T, Kawamoto K, Matsuno K, Ishihara G, Baba T, Komori N. Peripheral endothelial function can be improved by daily consumption of water containing over 7 ppm of dissolved hydrogen: A randomized controlled trial. PLoS One. 2020;15(5):e0233484. Published 2020 May 29. doi:10.1371/journal.pone.0233484

14. Peripheral arterial disease, hydrogen water

Gu, Q., Liu, B., Xue, J., Zhao, M., Zhang, X., Wang, M., Zhang, M., Xue, Y., Qin, S. (2020). Effects of drinking hydrogen-rich water in men at risk of peripheral arterial disease: a randomized placebo-controlled trial. 10.21203/rs.3.rs-136097/v1. https://doi.org/10.21203/rs.3.rs-136097/v1

Athletic Performance, Recovery, and Athlete Health

There are currently 23 publications on hydrogen therapy in humans, exploring various outcomes related to athletic performance, recovery, athlete health, and recovery from sports-induced injuries. The overwhelming majority of these studies is again using hydrogen water, with 17 of the publications on consuming hydrogen water orally (although one did not find a benefit), four studies using topical hydrogen water or hydrogen gel, two studies using hydrogen inhalation, and one study using hydrogen tablets intended to produce hydrogen gas within the body. This total adds to 24, not 23, as one of the studies used a two-pronged intervention of both the oral hydrogen tablets as well as the topical hydrogen-rich gel.

1. Enhances endurances and reduces fatigue, hydrogen water

Mikami et al, 2019. Drinking Hydrogen Water Enhances Endurance and Relieves Psychometric Fatigue: A Randomized, Double-Blind, Placebo-Controlled Study. Candian Journal of Physiology and Pharmacology.

2. Gut flora in female athletes, hydrogen water

Sha et al, 2018. Effects of the Long-Term Consumption of Hydrogen-Rich Water on the Antioxidant Activity and the Gut Flora in Female Juvenile Soccer Players From Suzhou, China. Medical Gas Research

3. Lowered submaximal heart rate in VO₂ max stress test, acute use of hydrogen water OUR HYDROGEN TABLETS

LeBaron et al., 2019. Acute Supplementation With Molecular Hydrogen Benefits Submaximal Exercise Indices. Randomized, Double-Blinded, Placebo-Controlled Crossover Pilot Study. Journal of Lifestyle Medicine.

4. VO₂ max and work completed, hydrogen water OUR HYDROGEN TABLETS

Ostojic et al., 2018. 28-Days Hydrogen-Rich Water Supplementation Affects Exercise Capacity in Mid-Age Overweight Women. Medicine & Science in Sports & Exercise.

5. Protection against free radical injury in athletes after high intensity exercise, hydrogen water

Sun & Sun, 2017. Selective Protective Effect of Hydrogen Water on Free Radical Injury of Athletes After High-Intensity Exercise. Biomedical Research.

6. Positive effects on redox status after 3 days of strenuous exercise, hydrogen water

Shibayama et al., 2017. Hydrogen-Rich Water Modulates Redox Status Repeated Three Consecutive Days of Strenuous Exercise. Medicine & Science in Sports & Exercise

7. Muscle fatigue, hydrogen water

Aokia et al., 2012. Pilot study: Effects of Drinking Hydrogen-Rich Water on Muscle Fatigue Caused by Acute Exercise in Elite Athletes. Medical Gas Research.

8. Prolonged intermittent exercise, hydrogen water

Da Ponte et al., 2017. Effects of Hydrogen Rich Water on Prolonged Intermittent Exercise. The Journal of Sports Medicine and Physical Fitness.

9. Exercise induced acidosis, hydrogen water

Drid et al., 2016. Is Molecular Hydrogen Beneficial to Enhance Post-Exercise Recovery in Female Athletes? Science & Sports.

10. Soft tissue injury in athletes, oral H₂ consumption + topical**

Ostojic et al., 2015. Effectiveness of Oral and Topical Hydrogen for Sports-Related Soft Tissue Injuries. Postgraduate Medicine.

11. Responses to exercise, hydrogen water

Botek et al., 2019. Hydrogen Rich Water Improved Ventilatory, Perceptual and Lactate Responses to Exercise. International Journal of Sports Medicine.

12. Hydrogen bathing on muscle fatigue, hydrogen water bath

Kawamura et al., 2016. Effects of Hydrogen Bathing on Exercise-Induced Oxidative Stress and Delayed-Onset Muscle Soreness. Western Pacific Region Index Medicus.

13. Koyama et al., 2008. Effect of Hydrogen Saturated Alkaline Electrolyzed Water on Urinary Oxidative Stress Markers After an Acute Exercise: A Randomized Controlled Trial. Anti-aging Med.***

14. Exercise recovery, hydrogen water

Drid et al., 2016. Molecular Hydrogen Affected Post-Exercise Recovery in Judo Athletes. Medicine & Science in Sports & Exercise

15. Female athletes, antioxidant capacity, hydrogen water

Minghao et al., 2017. Effects of Hydrogen-Rich Water on Antioxidant Capacity in Female Judo Athletes in Training.Chin J Sports Med. *IN CHINESE, ENGLISH ABSTRACT AVAILABLE

16. Lactic acid build up, exhaustive exercise, hydrogen water

Li Chen, 2015. Hydrogen Rich-Water on Blood Lactic Acid After Repeated Exhaustive Exercise. Journal of Taishan Medical College * IN CHINESE, ENGLISH ABSTRACT AVAILABLE

17. Case study Grade 2 ankle tear, topical hydrogen water OUR HYDROGEN TABLETS

Dejan Javorac, Valdemar Stajer. Case Report: Acute Hydrotherapy With Super-Saturated Hydrogen-Rich Water for Ankle Sprain in a Professional Athlete [Version 1; Peer Review: Awaiting Peer Review]

18. Exercise performance in healthy adults, hydrogen inhalation

Javorac D, Stajer V, Ratgeber L, Betlehem J, Ostojic SM, 2019. Short-Term H₂ Inhalation Improves Exercise Performance in Healthy Adults. Biology of Sport.

19. Acute ingestion for exercise performance, hydrogen water no results

Ooi, Ng and Omar, 2019. Acute Ingestion of Hydrogen-Rich Water Does Not Improve Incremental Treadmill Running Performance in Endurance-Trained Athletes. Applied Physiology and Research Metabolism

20. Physical activity of athletes, hydrogen water

Peng Wu, 2020. Hydrogen-Rich Water Improves the Physical Ability of Football Players and the Anti-Fatigue Ability of Rats, Revista Cientifica, Vol 30 No 1, (Volume 30, Issue 1.)

21. Acute hydrogen water in endurance athletes, Hydrogen water, very small benefit

Hiroto Ito, Shigeru Kabayma & Kazushige Goto, 2020. Effects of Electrolyzed Hydrogen Water Ingestion During Endurance Exercise in a Heated Environment on Body Fluid Balance and Exercise Performance.

Received 09 Nov 2019, Accepted 04 Feb 2020, Published online: 17 Apr 2020

22. Topical Hydrogen water vs RICE protocol for ankle tears, hydrogen water (OUR HYDROGEN TABLETS) add to sports and recovery

Res Sports Med. 2020 Dec 27; Hydrotherapy with hydrogen-rich water compared with RICE protocol following acute ankle sprain in professional athletes: a randomized non-inferiority pilot trial

23. Exercise recovery and exercise performance, hydrogen inhalation

Shibayama et al., 2020. The Effects Of Rich Hydrogen And Oxygen Mixed Gas Inhalation After High Intensity Exercise Influence On Exercise Performance Medicine & Science in Sports & Exercise: July 2020 - Volume 52 - Issue 7S - p 1024-1025 doi: 10.1249/01.mss.0000686736.01790.22

24. Muscular damage and soreness, hydrogen water bath

Nikola Todorovic et al., "The Effects of Supersaturated Hydrogen-Rich Water Bathing on Biomarkers of Muscular Damage and Soreness Perception in Young Men Subjected to High-Intensity Eccentric Exercise", Journal of Sports Medicine, vol. 2020, Article ID 8836070, 5 pages, 2020. https://doi.org/10.1155/2020/8836070

25. Acute use for exercise performance- Hydrogen water, unclear results

Michal Botek, Jakub Krejčí, Andrew J. McKune and Barbora Sládečková. Hydrogen-Rich Water Supplementation and Up-Hill Running Performance: Effect of Athlete Performance Level

26. Hydrogen water decreased lactic acid and lactate dehydrogenase following resistance training, hydrogen water.

Behrooz Moradi *, Ebrahim Saberi, Ali Hasani, Arash Montazer saheb: The role of drinking hydrogen-rich water produced by alkaline stick on resistance exercise in athletes

27. Hydrogen inhalation on exercise performance and post exercise stress markers, hydrogen inhalation

Graduate School Department of Interdisciplinary Research, University of Yamanashi, Yamanashi, Japan ,Date of Web Publication 25-Dec-2020,Impact of hydrogen-rich gas mixture inhalation through nasal cannula during post-exercise recovery period on subsequent oxidative stress, muscle damage, and exercise performances in men

28. Hydrogen creating capsules on ventilatory and ergogenic adjustments during exercise, hydrogen creating capsules

Alharbi Ahad Abdulkarim D , Naoyuki Ebine , Satoshi Nakae , Tatsuya Hojo , Yoshiyuki Fukuoka * Version 1 : Received: 24 December 2020 / Approved: 25 December 2020 / Online: 25 December 2020, Application of Molecular Hydrogen as an Antioxidant in Responses to Ventilatory and Ergogenic Adjustments during Incremental Exercise in Humans

29. Acute injury recovery, hydrogen-rich hydrotherapy

Alex Tarnava−, PUBLISHED: 2021-01-12 Supersaturated Hydrogen-Rich Water Hydrotherapy for Recovery of Acute Injury to the Proximal Phalanges on the 5th Toe: A Case Report

30. Physical performance of trained and untrained subjects, hydrogen water

Rafael Timón1,Guillermo Olcina1,Adrian González-Custodio1,Marta Camacho-Cardenosa1,Alba Camacho-Cardenosa1,Ismael Martínez Guardado1 , Effects of 7-day intake of hydrogen-rich water on physical performance of trained and untrained subjects

31. Muscle performance and oxidative stress after severe exercise, hydrogen water

2020, Shohei Dobashi, Kaito Takeuchi, Katsuhiro Koyama, Hydrogen-rich water suppresses the reduction in blood total antioxidant capacity induced by 3 consecutive days of severe exercise in physically active males

32. Increased peak oxygen uptake during incremental cycling exercise, hydrogen water

Hori A, Sobue S, Kurokawa R, Hirano Si, Ichihara M, Hotta N. Two-week continuous supplementation of hydrogenrich water increases peak oxygen uptake during an incremental cycling exercise test in healthy humans: a randomized, single-blinded, placebo-controlled study. Med Gas Res [serial online] 2020 [cited 2021 Feb 19];10:163-9. Available from: https://www.medgasres.com/text.asp?2020/10/4/163/304223

33. Muscle performance, hydrogen water

Botek, Michal & Krejci, Jakub & Mckune, Andrew & Valenta, Michal & Sládečková, Barbora. (2021). Hydrogen Rich Water Consumption Positively Affects Muscle Performance, Lactate Response, and Alleviates Delayed Onset of Muscle Soreness After Resistance Training. Journal of strength and conditioning research. 10.1519/JSC.0000000000003979.

34. Ventilatory and ergogenic adjustments during incremental exercise, H2-rich calcium powder

Alharbi AAD, Ebine N, Nakae S, Hojo T, Fukuoka Y. Application of Molecular Hydrogen as an Antioxidant in Responses to Ventilatory and Ergogenic Adjustments during Incremental Exercise in Humans. Nutrients. 2021; 13(2):459. https://doi.org/10.3390/nu13020459

Brain Recovery From Acute Injury, Neurological Conditions, and Brain Health

There are currently 13 publications exploring various neurological outcomes from hydrogen therapy in humans. Regarding hydrogen therapy and the brain, the methods are more spread out, with six of the 13 studies involving hydrogen water (although one did not find a benefit), five of the studies using hydrogen inhalation (although one did not find a benefit), and two of the studies using hydrogen-rich saline.

1. Mild cognitive impairment, hydrogen water

Ohta et al., 2017. Effects of Molecular Hydrogen Assessed by an Animal Model and a Randomized Clinical Study on Mild Cognitive Impairment. Current Alzheimer Research.

2. Improving outcomes of Alzheimer’s, hydrogen inhalation

Ono et al., 2018. Pilot Study on Therapeutic Inhalation of Hydrogen Gas for Improving Patients With Alzheimer’s Disease Assessed by Cognitive Subscale Scores and Magnetic Resonance Diffusion Tensor Imaging. Bioaccent.

3. Acute cerebral infarction, hydrogen inhalation

Ono et al., 2017. Hydrogen Gas Inhalation Treatment in Acute Cerebral Infarction: A Randomized Controlled Clinical Study on Safety and Neuroprotection. Journal of Stroke & Cerebrovascular

4. Acute cerebral ischemia, hydrogen inhalation

Ono et al., 2012. A Basic Study on Molecular Hydrogen (H₂) Inhalation in Acute Cerebral Ischemia Patients for Safety Check With Physiological Parameters and Measurement of Blood H₂ Level. Medical Gas Research.

5. Acute brain stem infarct, hydrogen saline + Edaravone

Ono et al., 2011. Improved Brain MRI Indices in the Acute Brain Stem Infarct Sites Treated With Hydroxyl Radical Scavengers, Edaravone and Hydrogen, as Compared to Edaravone Alone. A Non-Controlled Study. Medical Gas Research.

6. Acute cerebral infarction, hydrogen saline + Edaravone

Nagatani et al., 2013. Safety of Intravenous Administration of Hydrogen-Enriched Fluid in Patients With Acute Cerebral Ischemia: Initial Clinical Studies. Medical Gas Research.

7. Newborn abnormal neurological function, hydrogen water

Yang, Li and Chen, 2016. Hydrogen water reduces NSE, IL-6, and TNF-α levels in hypoxic-ischemic encephalopathy. Open Med

8. Parkinson’s, hydrogen water

Yoritaka et al., 2013. Pilot Study of H₂ Therapy in Parkinson's Disease: A Randomized Double-Blind Placebo-Controlled Trial. Movement Disorders.

9. Parkinson’s, no result, hydrogen water****

Yoritaka et al., 2018. Randomized, Double-Blind, Multicenter Trial of Hydrogen Water for Parkinson's Disease. Movement Disorders.

10. Parkinson’s, no result, hydrogen inhalation

Hiriyama et al., 2018. Inhalation of Hydrogen Gas Elevates Urinary 8-hydroxy-2′-deoxyguanine in Parkinson’s Disease Hiriyama et al., Medical Gas Research.

11. Concussion recovery case study, hydrogen water (OUR HYDROGEN TABLETS)

Javorac et al., 2019. Case Report: Buccal Administration of Hydrogen-Producing Blend After a Mild Traumatic Brain Injury in a Professional Athlete [Version 1; Peer Review: Awaiting Peer Review]. F1000 Research.

****This one needs some context. There were massive failures in this trial, namely there were mix ups in the placebo control group where they were intermittently given high doses of hydrogen in the water. Both placebo and control saw significant improvements over expectations and analysis against similar trials, but no benefit against each other. Both were receiving high dose hydrogen. One daily, the other perhaps every other day, and daily receiving at least 0.16mg/L cited in paped. The exact routine is unknown. There is currently underway a 52-week, 70 participant trial on PD in the USA. The registration can be found here

Regardless, we cannot state that H2 is beneficial for PD. We simply do not know. I cannot overstate this enough. We do not know, and it is unethical for marketers to push H2 for patients with PD. ***

12. Cognitive function in elderly, hydrogen inhalation

Korovljev D, Trivic T, Stajer V, Drid P, Sato B, Ostojic SM. 2019. Short-Term H₂ Inhalation Improves Cognitive Function in Older Women: A Pilot Study. International Journal of Gerontology.

13. Hydrogen water vs Caffeine for improving alertness after sleep deprivation, hydrogen water (our hydrogen tablets)

D Zanini, et al., 2020. Hydrogen vs. Caffeine for Improved Alertness in Sleep-Deprived Humans. Springer Link

14. Photobiomodulation on Parkinson disease, hydrogen water

Hong CT, Hu CJ, Lin HY, Wu D. Effects of concomitant use of hydrogen water and photobiomodulation on Parkinson disease: A pilot study. Medicine (Baltimore). 2021;100(4):e24191. doi:10.1097/MD.0000000000024191

Skin

There are currently 11 publications exploring various skin-related outcomes from hydrogen therapy in humans. Five of these studies used topical hydrogen water, three used consumed hydrogen water, two used hydrogen-rich saline, and one used hydrogen inhalation. This adds to 13 methods of administration of hydrogen therapy in 11 publications, as one of the studies explored the use of inhaled hydrogen, consumed hydrogen water, and hydrogen-rich saline simultaneously

1. Psoriasis, hydrogen water baths

Zhu et al., 2018. Positive Effects of Hydrogen-Water Bathing in Patients of Psoriasis and Parapsoriasis en Plaques. Scientific Reports.

2. Wrinkles reduction, hydrogen water baths

Kato et al., 2012. Hydrogen-Rich Electrolyzed Warm Water Represses Wrinkle Formation Against Uva Ray Together With Type-i Collagen Production and Oxidative-Stress Diminishment in Fibroblasts and Cell-Injury Prevention in Keratinocytes. Journal of Photochemistry and Photobiology.

3. Red skin/inflamed diseases, hydrogen saline

Ono et al., 2012. Hydrogen(H₂) Treatment for Acute Erythymatous Skin Diseases. A Report of 4 Patients With Safety Data and a Non-Controlled Feasibility Study With H₂ Concentration Measurement on Two Volunteers. Medical Gas Research.

4. Psoriasis, skin lesions, case studies, hydrogen water+saline+gas

Ishibashi et al., 2015. Improvement of Psoriasis-Associated Arthritis and Skin Lesions by Treatment With Molecular Hydrogen: A Report of Three Cases. Molecular Medicine Reports.

5. Pressure ulcers, hydrogen water

Li et al., 2013. Hydrogen Water Intake Via Tube-Feeding for Patients With Pressure Ulcer and Its Reconstructive Effects on Normal Human Skin Cells in Vitro. Medical Gas Research.

6. Graft vs. host disease case study, hydrogen water (drinking)

Qian & Shen, 2016. Successful Treatment With Hydrogen Rich Water in a Case of Chronic Graft-Versus-Host-Disease. Medical Gas Research.

7. UV damage in skin in vivo, topical hydrogen water******

Shin et al., 2013. Atomic Hydrogen Surrounded by Water Molecules, H(H₂O)m, Modulates Basal and UV-Induced Gene Expressions in Human Skin in Vivo. PLOS One.

8. Keratin plugged hair pores, hydrogen water baths

Tanaka et al., 2018. Electrolytically Generated Hydrogen Warm Water Cleanses the Keratin-Plug-Clogged Hair-Pores and Promotes the Capillary Blood-streams, More Markedly Than Normal Warm Water Does. Medical Gas Research.

9. Visceral fat and skin blotches, hydrogen water baths

Asada R, et al., 2019. Effects of Hydrogen-Rich Water Bath on Visceral Fat and Skin Blotch, With Boiling-Resistant Hydrogen Bubbles. Medical Gas Research

10. Skin aging and antioxidant activity, hydrogen water mask

Int. J. Mol. Sci. 2020, 21(24), 9731; Antioxidant Activity of Hydrogen Water Mask Pack Composed of Gel-Type Emulsion and Hydrogen Generation Powder

11. Heat retention effects, hydrogen baths

https://www.sciencedirect.com/science/article/abs/pii/S0306456520305763

12. Acne vulgaris in adult women, topical hydrogen purification

Chilicka, K., Rogowska, A., Szyguła, R. (2021). Effects of Topical Hydrogen Purification on Skin Parameters and Acne Vulgaris in Adult Women. Healthcare. 9(2). 144. https://doi.org/10.3390/healthcare9020144.

Rheumatoid Arthritis

Despite early and promising results, there are only two clinical trials exploring the benefits of hydrogen therapy for rheumatoid arthritis. In one of the studies, results were seen from high-dose hydrogen water, and in the other study, from hydrogen-rich saline.

1. Rheumatoid arthritis, hydrogen saline

Ishibashi et al., 2014. Therapeutic Efficacy of Infused Molecular Hydrogen in Saline on Rheumatoid Arthritis: A Randomized, Double-Blind, Placebo-Controlled Pilot Study. International Immunopharmacology.

2. Rheumatoid arthritis, hydrogen water

Ishibashi et al., 2012. Consumption of Water Containing a High Concentration of Molecular Hydrogen Reduces Oxidative Stress and Disease Activity in Patients With Rheumatoid Arthritis: An Open-Label Pilot Study. Medical Gas Research.

Dialysis

There are currently six publications on human trials using hydrogen therapy for patients on dialysis, all of which delivered the hydrogen gas via hydrogen-rich saline.

1. Peritoneal dialysis, hydrogen rich dialysate

Terawaki et al., 2013. Transperitoneal Administration of Dissolved Hydrogen for Peritoneal Dialysis Patients: A Novel Approach to Suppress Oxidative Stress in the Peritoneal Cavity. Medical Gas Research.

2. Kidney dialysis for inflammation, hydrogen saline

Nakayama et al., 2010. A Novel Bioactive Haemodialysis System Using Dissolved Dihydrogen (H₂) Produced by Water Electrolysis: A Clinical Trial. Nephrology Dialysis Transplantation.

3. Low hydrogen dialysis

Nakayama et al., 2009. Biological Effects of Electrolyzed Water in Hemodialysis. Nephron Clinical Practice.

4. Improvement in chronic dialysis patients, hydrogen rich dialysis

Nakayama et al., 2018. Novel Haemodialysis (HD) Treatment Employing Molecular Hydrogen (H₂)-Enriched Dialysis Solution Improves Prognosis of Chronic Dialysis Patients: A Prospective Observational Study. Scientific Reports

5. Improvement of the fraction of human mercaptalbumin on hemodialysis treatment, hydrogen rich dialysis

Maeda et al, 2016. Improvement of the Fraction of Human Mercaptalbumin on Hemodialysis Treatment Using Hydrogen-Dissolved Hemodialysis Fluid: A Prospective Observational Study. Renal Replacement Therapy.

6. Interim analysis, observational improvements over 12 months in 262 patients on dialysis, hydrogen rich dialysis

Nakayama et al., 2017. Possible clinical Effects of Molecular Hydrogen (H₂) Delivery During Hemodialysis in Chronic Dialysis Patients: Interim Analysis in a 12 Month Observation. PLOS One

Chemo & Radiation Side Effect Reduction

There are currently two published clinical trials exploring the efficacy of hydrogen therapy for the reduction of side effects associated with chemotherapy and radiation therapy. Both of these trials used hydrogen water as the delivery method.

1. Reduction in side effects in radiation therapy cancer patients, hydrogen water

Kang et al., 2011. Effects of Drinking Hydrogen-Rich Water on the Quality of Life of Patients Treated With Radiotherapy for Liver Tumors. Medical Gas Research.

2. Improved liver function on patients on chemotherapy, hydrogen water

Yang et al., 2017. Protective Effect of Hydrogen-Rich Water on Liver Function of Colorectal Cancer Patients Treated With Mfolfox6 Chemotherapy. Molecular and Clinical Onocology.

Cancer

There are currently three published articles on the use of hydrogen therapy in cancer patients to address the cancer itself. All three of these trials used hydrogen inhalation as the delivery method.

1. Colorectal cancer, hydrogen gas inhalation

Akagi & Baba, 2019. Hydrogen gas restores exhausted CD8+ T cells in patients with advanced colorectal cancer to improve prognosis. Oncology Reports.

2. Stage III and Stage IV cancer, cohort, hydrogen inhalation

Chen JB, et al., 2019. "Real World Survey" of Hydrogen-Controlled Cancer: A Follow-Up Report of 82 Advanced Cancer Patients. Medical Gas Research

3. Case study gallbladder cancer, hydrogen inhalation

Chen J, et al., 2019. A Gallbladder Carcinoma Patient With Pseudo-Progressive Remission After Hydrogen Inhalation. OncoTargets andTherapy. Chen J, et al., 2019. Hydrogen Gas Therapy Induced Shrinkage of Metastatic Gallbladder Cancer: A Case Report. World J Clin Cases.

4. Bone marrow, hydrogen inhalation

Yoshiyasu Takefuji, Protective effect of hydrogen gas inhalation on radiation-induced bone marrow damage in cancer patients: a retrospective observational study

5. Lung cancer, hydrogen gas

Hydrogen gas activates coenzyme Q10 to restore exhausted CD8+ T cells, especially PD‑1+Tim3+terminal CD8+ T cells, leading to better nivolumab outcomes in patients with lung cancer

6. Non-small cell lung cancer, hydrogen inhalation

Chen, J. B., Kong, X. F., Qian, W., Mu, F., Lu, T. Y., Lu, Y. Y., & Xu, K. C. (2020). Two weeks of hydrogen inhalation can significantly reverse adaptive and innate immune system senescence patients with advanced non-small cell lung cancer: a self-controlled study. Medical gas research, 10(4), 149–154. https://doi.org/10.4103/2045-9912.304221

Antioxidant

There are four publications that exclusively explore hydrogen therapy for its antioxidant-like behavior in humans. All four of these trials used hydrogen water as the delivery method.

1. Serum antioxidant status in healthy men, hydrogen water

Trivic et al., 2017. Drinking Hydrogen-Rich Water for 4 Weeks Positively Affects Serum Antioxidant Enzymes in Healthy Men: A Pilot Study. Current Topics in Nutraceutical Research

2. Blood alkalization, hydrogen water

Trivic et al., 2017. Drinking Hydrogen-Rich Water for 4 Weeks Positively Affects Serum Antioxidant Enzymes in Healthy Men: A Pilot Study. Current Topics in Nutraceutical Research.

3. Hydrogen water

Shimminju (doctoral dissertation). Effects of H₂-Rich Water Consumption on Oxidative ... Randomized, Double-Blind, Controlled Study.
MARKED AS 2018

4. Antioxidant capacity, hydrogen water

Hiraoka et al., 2006. Effects of Drinking a Water Product with Anti-Oxidant Activities In Vitro on the Blood Levels of Biomarker Substances for the Oxidative Stress Journal of Health Science.

Other

There are 12 other publications on molecular hydrogen research/ trials with humans that do not fall under any of the previous umbrella categories but explore the use of hydrogen therapy for a beneficial response. Nine of these 12 trials used hydrogen water as the delivery method, although one did not find a statistically significant result but did note a potential responder group. The remaining three trials all used hydrogen inhalation.

1. Hepatitis B, hydrogen water

Xia et al., 2013. Effect of Hydrogen-Rich Water on Oxidative Stress, Liver Function, and Viral Load in Patients With Chronic Hepatitis B. Clinical and Translational Science.

2. Post-cardiac arrest, hydrogen inhalation

Tamura et al., 2016. Feasibility and Safety of Hydrogen Gas Inhalation for Post-Cardiac Arrest Syndrome – First-in-Human Pilot Study. Circulation Journal.

3. Heart surgery, hydrogen inhalation

Katsumata et al., 2017. 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

Circ J. 2017

4. Hydrogen-rich water for improvements of mood, anxiety and autonomic nerve function in daily life, hydrogen water

Mizuno et al., 2017. Hydrogen-Rich Water for Improvements of Mood, Anxiety, and Autonomic Nerve Function in Daily Life. Medical Gas Research

5. Periodontitis and antioxidant status, hydrogen water

Azuma et al., 2015. Drinking Hydrogen-Rich Water Has Additive Effects on Non-Surgical Periodontal Treatment of Improving Periodontitis: A Pilot Study. Antioxidants.

6. Blood alkalization, hydrogen water

Ostojic et al, 2012. Serum Alkalinization and Hydrogen-Rich Water in Healthy Men. Mayo Clinic Proceedings.

7. Blood alkalization, hydrogen water

Ostojic & Stojanovic, 2012. Hydrogen-Rich Water Affected Blood Alkalinity in Physically Active Men. Research in Sports Medicine.

8. Painful bladder syndrome, hydrogen water (did not work, potential small responder group)

Matsumoto et al., 2013. Effect of Supplementation With Hydrogen-Rich Water in Patients With Interstitial Cystitis/Painful Bladder Syndrome. Urology

9. Fecal matter and reported sleep function, hydrogen water

Tanaka et al., 2018. Daily Ingestion of Alkaline Electrolyzed Water Containing Hydrogen

Influences Human Health, Including Gastrointestinal Symptoms. Medical Gas Research.

10. Tracheal Stenosis (cause not stated, radiation therapy?), hydrogen inhalation

Zhou ZQ, et al., 2019. Breathing Hydrogen-Oxygen Mixture Decreases Inspiratory Effort in Patients With Tracheal Stenosis.
Respiration

11. Gastroesophageal reflux disease (GERD), hydrogen-rich water

Franceschelli S, Gatta DMP, Pesce M, Ferrone A, Di Martino G, Di Nicola M, De Lutiis MA, Vitacolonna E, Patruno A, Grilli A, Felaco M, Speranza L.2018. Modulation of the Oxidative Plasmatic State In Gastroesophageal Reflux Disease With The Addition of Rich Water Molecular Hydrogen: A New Biological Vision. Journal of Cellular and Molecular Medicine. 2018 May; 22(5):2750-2759. doi: 10.1111/jcmm.13569. Epub 2018 Mar 7. PMID: 29512923; PMCID: PMC5908129.

12. Inflammation and apoptosis reduction in healthy individuals, hydrogen water

Sim, M., Kim, C., Shon, W. et al., 2020. Hydrogen-rich water reduces inflammatory responses and prevents apoptosis of peripheral blood cells in healthy adults: a randomized, double-blind, controlled trial. Sci Rep 10, 12130

13. Disease severity and dyspnea in Covid-19 patients, hydrogen inhalation

J Thorac Dis. 2020 Jun; .Hydrogen/oxygen mixed gas inhalation improves disease severity and dyspnea in patients with Coronavirus disease 2019 in a recent multicenter, open-label clinical trial

14. Therapeutic effects on Chronic graft-versus-host-disease (cGVHD) patients, hydrogen water

Qian Liren, Liu Miao, Shen Jianliang, Cen Jian, Zhao Defeng. 2020. Hydrogen in Patients With Corticosteroid-Refractory/Dependent Chronic Graft-Versus-Host-Disease: A Single-Arm, Multicenter, Open-Label, Phase 2 Trial.Frontiers in Immunology

15. Allergic rhinitis treatment, hydrogen-rich saline

Jin L, Fan K, Zhang X, Zhao Y, Ge Q, Wang Y, Yu S. [Changes of nasal nitric oxide in the treatment of allergic rhinitis with hydrogen-rich saline lavage of nasal cavity]. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2020 Mar;34(3):244-247. Chinese. doi: 10.13201/j.issn.2096-7993.2020.03.014. PMID: 32791592.

16. Corneal endothelial damage prevention during phacoemulsification, H2 dissolved in an irrigation solution

Igarashi T, Ohsawa I, Kobayashi M, Umemoto Y, Arima T, Suzuki H, Igarashi T, Otsuka T, Takahashi H. Effects of Hydrogen in Prevention of Corneal Endothelial Damage During Phacoemulsification: A Prospective Randomized Clinical Trial. Am J Ophthalmol. 2019 Nov;207:10-17. doi: 10.1016/j.ajo.2019.04.014. Epub 2019 May 9. PMID: 31077667.

17. Prevention of dry eye disease, hydrogen H2-producing milk

Motoko Kawashima, Saki Tsuno, Mitsuharu Matsumoto, Kazuo Tsubota, Hydrogen-producing milk to prevent reduction in tear stability in persons using visual display terminals,The Ocular Surface,Volume 17, Issue 4,2019,https://doi.org/10.1016/j.jtos.2019.07.008

18. Immune function of middle-aged participants, hydrogen inhalation

Chen, J. B., Kong, X. F., Qian, W., Mu, F. (2021). High-flow hydrogen inhalation might suppresses the immune function of middle-aged participants: a self-controlled study. Medical gas research, 11(1), 12-17.

19. Oxidative stress in post-cardiac arrest syndrome, hydrogen gas inhalation

Tamura, T., Suzuki M., Hayashida K., Kobayashi Y., Yoshizawa J., Shibusawa T., Sano M., Hori S., Sasaki J. (2020). Hydrogen gas inhalation alleviates oxidative stress in patients with post-cardiac arrest syndrome. Journal of Clinical Biochemistry and Nutrition, 67(2)- 214-221.https://doi.org/10.3164/jcbn.19-101

20. Heart surgery under cardiopulmonary bypass, hydrogen inhalation

Danilova D.A., Brichkin Yu.D., Medvedev A.P., Pichugin V.V., Fedorov S.A., Taranov E.V., Nazarov E.I., Ryazanov M.V., Bolshukhin G.V., Deryugina A.V. (2021). Application of Molecular Hydrogen in Heart Surgery under Cardiopulmonary Bypass. Sovremennye Tehnologii v Medicine. 13(1): 71–77, https://dx.doi.org/10.17691/stm2021.13.1.09

Electrically Reduced Water and Magnesium-Based Ingestible Interventions for “-ORP”

“Ionized water” or “electrolyzed water” uses electrolysis and dissolves H2 gas in varying amounts into the water. This is what gives it the negative “ORP.” Likewise, elemental magnesium-based products designed for a “negative ORP” were creating said “negative ORP” by generating molecular hydrogen. That said, exact dosages and concentrations are not known from these studies, so we have segmented them off from the “molecular hydrogen research.”

1. “Ionized water” diarrhea

Tashiro, H., Hokudo, T., Ono, H., Fujiyama, Y., & Baba, T. (2000). Clinical evaluation of alkaline ionized water for abdominal complaints: Placebo controlled double blind tests. Digestion & Absorption.

2. “Electrolyzed reduced water” in dialysis

Huang, K.-C., Yang, C.-C., Lee, K.-T., & Chien, C.-T. (2003). Reduced hemodialysis-induced oxidative stress in end-stage renal disease patients by electrolyzed reduced water. Kidney International, 64(2), 704–14. https://doi.org/10.1046/j.1523-1755.2003.00118.x.

3. “Anti-oxidant water”

Hiraoka, A., Sasaki, S., Yamada, T., Shinohara, A., & Chiba, M. (2006). Effects of drinking a water product with anti-oxidant activities in vitro on the blood levels of biomarker substances for the oxidative stress. Journal of Health Science https://doi.org/10.1248/JHS.52.817

Cites hydrogen gas as the antioxidant, no indication of concentration. Cites higher in vitro abilities than observed in vivo without understanding in vitro data using the same concentrations, as in vivo will not be close to relatable/transferable

4. “Electrolyzed reduced water” in dialysis end-stage renal patients

Huang, K.-C., Yang, C.-C., Hsu, S.-P., Lee, K.-T., Liu, H.-W., Morisawa, S., Otsubo, K., & Chien, C.-T. (2006). Electrolyzed-reduced water reduced hemodialysis-induced erythrocyte impairment in end-stage renal disease patients. Kidney International, 70(2), 391–8. https://doi.org/10.1038/sj.ki.5001576.

5. Negative ion eater-performance

Bittner, A. C., Bittner, R. C. L., Lile, Jr., K., & Sakuragi, Y. (2007). Intra-individual ergonomics (I2E): Performance effects of ultra-negative-ion water. https://doi.org/10.1177/154193120705102604.

6.Alkaline reduced water, diabetes

Yang, E. J., Kim, J. R., Ryang, Y. S., Kim, D. H., Deung, Y. K.,Park, S. K.,& Lee, K. J. (2007).A clinical trial of orally administered alkaline reduced water.

7. Electrolyzed water, dialysis

Nakayama, M., Kabayama, S., Nakano, H., Zhu, W.-Z., Terawaki, H., Nakayama, K., Katoh, K., Satoh, T., & Ito, S. (2009) Biological effects of electrolyzed water in hemodialysis. Nephron Clinical Practice, 112(1), c9–15. https://doi.org/10.1159/000210569.

8. Electrolyzed water, end stage renal patients dialysis

Huang, K.-C., Hsu, S.-P., Yang, C.-C., Yang, P. O., Lee, K.-T., Morisawa, S., Otsubo, K., & Chien, C.-T. (2010). Electrolysed-reduced water dialysate improves T-cell damage in end-stage renal disease patients with chronic haemodialysis. Nephrol Dial Transplant, 25(8) 2730–7. https://doi.org/10.1093/ndt/gfq082.

9. Negative ORP blend, magnesium-based sports performance

Ostojic, S. (2011). Drinks with alkaline negative oxidative reduction potential improve exercise performance in physically active men and women: Double-blind, randomized, placebo-controlled, cross-over trial of efficacy and safety. Serbian Journal of Sports Sciences.

10. “Hydrogen containing” ionized water

Tanaka, Y., Saihara, Y., Izumotani, K., & Nakamur, H.(2018). Daily ingestion of alkaline electrolyzed water containing hydrogen influences human health, including gastrointestinal symptoms. Medical Gas Research, 8(4), 160–166. https://doi.org/10.4103/2045-9912.248267

11. Electrolyzed water, type 2 diabetes

Rias, Y. A., Kurniawan, A. L., Change, C. W., Gordon, C. J., & Tsai, H. T. (2020). Synergistic effects of regular walking and alkaline electrolyzed water on decreasing inflammation and oxidative stress, and increasing quality of life in individuals with type 2 diabetes: A community based randomized controlled trial. Antioxidants, 9(10), 946. https://doi.org/10.3390/antiox9100946.

12. Other studies listed at http://www.molecularhydrogeninstitute.com/human-studies

There are a further four trials listed at http://www.molecularhydrogeninstitute.com/human-studies near the bottom with no links to journals and that I have never been able to find. There is a strong possibility they were never written or published in English.

Fujiyama, Y. & Kitahora, T. (2004). Alkaline electrolytic water (alkali ions water) for drinking water in medicine. Mizu no Tokusei to Atarashii Riyo Gijutsu, Enu-Ti-Esu, Tokyo, 348–457.

Lee, K.J., et al., Effect of electrolyzed-reduced water: In vivo and in vitro examination and clinical trials, in the 3rd Asia Pacific conference on evidence-based medicine. Hong Kong.

Lu, K. C., et al. (2006). Electrolyzed reduced water attenuates hemodialysis-induced mononuclear cells apoptosis in end-stage renal disease patients. Nephrology Dialysis Transplantation, 21, 200–201.

Yeung, L. K., et al. (2006). Effect of electrolyzed reduced water hemodialysis on peripheral lymphocyte intracellular cytokine expression. Nephrology Dialysis Transplantation, 21, 204–204.

Magnesium Implants

Researchers in the field of biodegradable magnesium implants are certainly aware that the degradation of the magnesium produces molecular hydrogen. They even use hydrogen gas creation to map the degradation of the implants.^[i] However, they seem unaware of any potential therapeutic benefits of said molecular hydrogen, and as such, none of these studies mention anything relevant in order to ascertain dosages and benefits of the hydrogen gas, such as mass of magnesium needed to extrapolate hydrogen creation or rate of reaction. These studies should be tracked, nonetheless, in the event they may be included into the molecular hydrogen therapy story in the future.

^[i] https://link.springer.com/article/10.1007/s11837-020-04052-4 Zhao, D., Wu, J., Chou, D.-T., Hoagland, W., Benson, D., Dong, Z., Kumta, P. N., & Heineman, W. R. (2020). Visual hydrogen mapping sensor for noninvasive monitoring of bioresorbable magnesium implants in vivo. JOM, 72, 1851–1858. https://doi.org/10.1007/s11837-020-04052-4.

1. Biodegradation mechanism of Mg alloy

Lee, J.-W., Han, H.-S., Han, K.-J.,Park, J., Jeon, H., Ok, M.-R., Seok, H.-K., Ahn, J.-P., Lee, K. E., Lee, D.-H., Yang, S.-J., Cho,S.-Y., Cha, P.-R.,Kwon, H., Nam, T.-H., Han, J. H. L., Rho, H.-J., Lee, K.-S., Kim, Y.-C., & Mantovani, D. (2016). Long-term clinical study and multiscale analysis of in vivo biodegradation mechanism of Mg alloy. Proceedings of the National Academy of Sciences of the United State of America, 113(3), 716–21. https://doi.org/10.1073/pnas.1518238113.

2. Magnesium-based screws in hallux valgus surgery

Plaass, C., Ettinger, S., Sonnow, L., Koenneker, S., Noll, Y., Weizbauer, A., Reifenrath, J., Claassen, L., Daniilidis, L., Stukenborg-Colsman, C., & Windhagen, H. (2016). Early results using a biodegradable magnesium screw for modified chevron osteotomies. Journal of Orthopaedic Research, 34(12), 2207–2214. https://doi.org/10.1002/jor.23241.

3. Magnesium implants for fixation of distal metatarsal osteotomies

Plaass, C., von Falck, C., Ettinger, S., Sonnow, L., Calderone, F., Weizbauer, A., Reifenrath, J., Claassen, L., Waizy, H., Daniilidis, K., Stukenborg-Colsman, C., & Windhagen, H. Bioabsorbable magnesium versus standard titanium compression screws for fixation of distal metatarsal osteotomies — 3 year results of a randomized clinical trial. Journal of Orthopaedic Science, 23(2), 321–327. https://doi.org/10.1016/j.jos.2017.11.005.

4. Biodegradable magnesium screw in vascularized bone graft implantation

Zhao, D., Huang, S., Lu, F., Wang, B., Yang, L., Qin, L., Yang, K., Li, Y., Li, W., Wang, W., Tian, S., Zhang, S., Gao, W., Wang, Z., Zhang, Y., Xie, X., Wang, J., & Li, J. (2016). Vascularized bone grafting fixed by biodegradable magnesium screw for treating osteonecrosis of the femoral head. Biomaterials, 81, 84–92. https://doi.org/10.1016/j.biomaterials.2015.11.038.

5. Biodegradable magnesium screws for displaced femoral neck fracture in young adults

Yu, X., Zhao, D., Huang, S., Wang, B., Zhang, X., Wang, W., & Wei, X. (2015). Biodegradable magnesium screws and vascularized iliac grafting for displaced femoral neck fracture in young adults. BMC Musculoskeletal Disorders, 16, 329. https://doi.org/10.1186/s12891-015-0790-0.

6.Bone response to magnesium (Mg) ion-incorporated titanium (Ti) implants and healing

Hieu, P. D., Baek, D. H., Park, D. S., Park, J. T., & Hong, K. S.Evaluation of stability changes in magnesium-incorporated titanium implants in the early healing period. The Journal of Craniofacial Surgery, 24(5), 1552–7. https://doi.org/10.1097/SCS.0b013e318290264b.