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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 over 120. 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 128 publications on hydrogen therapy in humans. The majority, 68, cover drinking hydrogen water. Hydrogen inhalation is a distant second with 25 publications, hydrogen-rich saline is third with 11 publications, and topical hydrogen therapy has ten 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, and several additional methods. This totals 130 administration methods because in two of the publications more than one delivery method of hydrogen therapy was used.

Of the 124 human trials, four did not find a benefit. But 120 did, which is a 97% 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

There are currently 15 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 twelve of the 15 publications. Two publications discuss ways to produce molecular hydrogen within the body, and one discusses hydrogen inhalation.

1. Diabetes Type 2, Hydrogen Water

Kajiyama, S., Hasegawa, G., Asano, M., Hosoda, H., Fukui, M., Nakamura, N.,  Kitawaki, J., Imai, S., Nakano, K., Ohta, M., Adachi, T., Obayashi, H., & Yoshikawa, T. (2008). Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. Nutrition Research, 28(3): 137–43.

2. Metabolic Syndrome, Hydrogen Water

Nakao, A., Toyoda, Y., Sharma , P., Evans , M., & Guthrie, N. (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, 46(2): 140–149.

3. Metabolic Syndrome, Hydrogen Water

Song, G., Li, M., Sang, H., Zhang, L., Li, X., Yao, S., Yu, Y., Zong, C., Xue, Y., & Qin, S. (2013). Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome. Journal of Lipid Research, 54(7): 1884–93

4. High Cholesterol, Hydrogen Water

Song, G., Lin, Q.,   Zhao, H., Liu, M., Ye, F., Sun, Y., Yu, Y., Guo, S., Jiao, P., Wu, Y., Ding, G., Xiao, Q., & Qin, S.   (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, The Journal of Clinical Endocrinology & Metabolism, 100 (7): 2724–33.

5. Mitochondrial and Inflammatory Myopathies, Hydrogen Water

Ito , M., Ibi, T. Sahashi, K., Ichihara , M.,  Ito , M.,& Ohno, K. (2011). Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies. Medical Gas Research, 1, 24.

6. Body Comp/Metabolism, Oral H2 Tablets

Korovljev, D., Trivic, T., Drid, P., & Ostojic, S. M. (2018). Molecular hydrogen affects body composition, metabolic profiles, and mitochondrial function in middle-aged overweight women. Irish Journal of Medical Science, 87 (1): 85–89.

7. Non-Alcoholic Fatty Liver Disease (NAFLD), Hydrogen Water OUR HYDROGEN TABLETS

Korovljev, D. & Ostojic, S. M. (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, 4 (6): 688693.

8. Secondary Analysis on NAFLD via HOMA2-Insulin Sensitivity, Hydrogen Water OUR HYDROGEN TABLETS

Korovljev, D., Javorac, D., Stajer, V., & Ostojic, S. M. (2019). Hydrogen-rich water positively affects homa2 variables in physically inactive population. Abstracts from the 5th International Scientific Conference on Exercise and Quality of Life, 3. BMC Sports Science, Medicine and Rehabilitation, 11 (1): 7.

9. Vascular Endothelial Function, Hydrogen Water, High Acute Dose

Sakai, T., Sato B., Hara , K., Hara, Y., Naritomi, Y., Koyanagi, S., Hara, H., Nagao, T., & Ishibashi, T. (2014). Consumption of water containing over 3.5 mg of dissolved hydrogen could improve vascular endothelial function. Vascular Health and Risk Management, 10, 591–597.

10. Cardiometabolic Risk Factors in Elderly, Hydrogen Inhalation

Korovljev, D., Stajer, V., Javorac, D., & Ostojic, S. M. (2018). Hydrogen inhalation positively affects cardiometabolic risk factors in men and women aged 65 years or older: A preliminary report. European Geriatric Medicine, 9, 729–730.

11. Reduction in IL-1b mRNA in Peripheral Blood in Type 2 Diabetics Post Meal, Acarbose for Internal H2Production*

Tamasawa, A. & Osonoi, T. (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, 762, 96101. 

12. Body Composition, Blood Lipid Profiles and Inflammation Biomarkers in Men and Women With Metabolic Syndrome, Hydrogen Water OUR HYDROGEN TABLETS

LeBaron, T. W., Singh, R.B., Fatima, G., Kartikey, K., Sharma, J. P., Ostojic, S. M., Gvozdjakova, A., Kura, B., Noda, M., Mojto, V., Niaz, M. A., & Slezak, J. (2020). 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 Metabolic Syndrome and Obesity, 13, 889–896.

13. Peripheral Endothelial Function, Hydrogen Water

Ishibashi, T., Kawamoto, K., Matsuno, K., Ishihara, G., Baba, T., & Komori, N. (2020). Peripheral endothelial function can be improved by daily consumption of water containing over 7 ppm of dissolved hydrogen: A randomized controlled trial. PLoS One,15(5): e0233484.

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. ResearchGate.

15. Antioxidant Activity, Diabetes and DNA-Oxidative Injuries, Hydrogen Water

Asada, R., Tazawa, K., Sato, S., & Miwa, N. (2020). Effects of hydrogen-rich water prepared by alternating-current-electrolysis on antioxidant activity, DNA oxidative injuries, and diabetes-related markers. Medical Gas Research, 10(3), 114–121.

16. A randomized, placebo-controlled clinical trial of hydrogen/oxygen inhalation for non-alcoholic fatty liver disease

Geru Tao, Guangjie Zhang, Wei Chen,Chao Yang,Yazhuo Xue, Guohua Song, Shucun Qin (2022) A randomized, placebo-controlled clinical trial of hydrogen/oxygen inhalation for non-alcoholic fatty liver disease.

17. Biological Effects of Hydrogen Water on Subjects with NAFLD

Kura B, Szantova M, LeBaron TW, Mojto V, Barancik M, Szeiffova Bacova B, Kalocayova B, Sykora M, Okruhlicova L, Tribulova N, Gvozdjakova A, Sumbalova Z, Kucharska J, Faktorova X, Jakabovicova M, Durkovicová Z, Macutek J, Koscová M, Slezak J. Biological Effects of Hydrogen Water on Subjects with NAFLD: A Randomized, Placebo-Controlled Trial. Antioxidants. 2022; 11(10):1935

18. The effect of a low dose hydrogen-oxygen mixture inhalation in midlife/older adults with hypertension: A randomized, placebo-controlled trial

Liu B, Jiang X, Xie Y, Jia X, Zhang J, Xue Y and Qin S (2022) The effect of a low dose hydrogen-oxygen mixture inhalation in midlife/older adults with hypertension: A randomized, placebo-controlled trial. Front. Pharmacol. 13:1025487. doi: 10.3389/fphar.2022.1025487

19. Efficacy and Safety of Hydrogen Inhalation Therapy in Type 2 Diabetes

Lin Guihua, Ni Tongsu. Efficacy and safety of hydrogen inhalation therapy in patients with type 2 diabetes mellitus with poor response to metformin [J]. Advances in Clinical Medicine, 2022, 12(10): 9605-9612.

20. Effectiveness and safety of hydrogen inhalation as an adjunct treatment in Chinese type 2 diabetes patients

Zhao Z, Ji H, Zhao Y, Liu Z, Sun R, Li Y and Ni T (2023) Effectiveness and safety of hydrogen inhalation as an adjunct treatment in Chinese type 2 diabetes patients: A retrospective, observational, double-arm, real-life clinical study. Front. Endocrinol. 13:1114221. doi: 10.3389/fendo.2022.1114221

Athletic Performance, Recovery, and Athlete Health

There are currently 36 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 26 of the publications on consuming hydrogen water orally (although one did not find a benefit), four studies using topical hydrogen water or hydrogen gel, four studies using hydrogen inhalation, one study using hydrogen tablets intended to produce hydrogen gas within the body, one study with H2-rich calcium powder and one study using H2-infused beverage. This total adds to 37, not 36, 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, T., Tano, K., Lee, H., Lee, H., Park, J., Ohta, F., LeBaron, T. W., & Ohta, S. (2019). Drinking hydrogen water enhances endurance and relieves psychometric fatigue: a randomized, double-blind, placebo-controlled study. Canadian Journal of Physiology and Pharmacology, 97(9): 857–862. 

2. Gut Flora in Female Athletes, Hydrogen Water
Sha, J.-B., Zhang, S.-S., Lu, Y.-M., Gong, W.-J., Jiang, X.-P., Wang, J.-J., Qiao, T.-L., Zhang, H.-H., Zhao, M.-Q., Wang, D.-P., Xia, H., Li, Z.-W., Chen, J.-L., Zhang, L., & Zhang, C.-G. (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, 8(4): 135–143. 

3. Lowered Submaximal Heart Rate in VO2Max Stress Test, Acute Use of Hydrogen Water OUR HYDROGEN TABLETS
LeBaron, T. W., Larson, A. J., Ohta, S., Mikami, T., Barlow, J. Bullock, J., & DeBeliso, M. (2019). Acute supplementation with molecular hydrogen benefits submaximal exercise indices. randomized, double-blinded, placebo-controlled crossover pilot study. Journal of Lifestyle Medicine, 9(1): 36–43. 

4. VO2Max and Work Completed, Hydrogen Water OUR HYDROGEN TABLETS
Ostojic, S., Korovljev, D., Stajer, V., & Javorac, D. (2018). 28-days hydrogen-rich water supplementation affects exercise capacity in mid-age overweight women. Medicine & Science in Sports & Exercise, 50(5S): 728–729. 

5. Protection Against Free Radical Injury in Athletes After High Intensity Exercise, Hydrogen Water

Sun, Y.-P. & Sun, L. 2017. Selective protective effect of hydrogen water on free radical injury of athletes after high-intensity exercise. Biomedical Research, 28(10).  

6. Positive Effects on Redox Status After 3 Days of Strenuous Exercise, Hydrogen Water
Shibayama, Y.; Takeuchi, K., Dobashi, S., & Koyama, K. (2017). Hydrogen-rich water modulates redox status repeated three consecutive days of strenuous exercise. Medicine & Science inMedicine & Science inSports & Exercise, 49(5S): 941.

7. Muscle Fatigue, Hydrogen Water
Aokia, K., Nakao, A., Adachi, T., Matsui, Y., & Miyakawa, S. (2012). Pilot study: Effects of drinking hydrogen-rich water on muscle fatigue caused by acute exercise in elite athletes. Medical Gas Research, 2, 12.

8. Prolonged Intermittent Exercise, Hydrogen Water
Da Ponte, A., Giovanelli, N., Nigris, D., & Lazzer, S. (2017). Effects of hydrogen rich water on prolonged intermittent exercise. The Journal of Sports Medicine and Physical Fitness, 58(5): 612–621. 

9. Exercise Induced Acidosis, Hydrogen Water
Drid, P., Trivic, T., Casals, C., Trivic, S., Stojanovic, M., & Ostojic, S. M. (2016). Is molecular hydrogen beneficial to enhance post-exercise recovery in female athletes? Science & Sports. 

10. Soft Tissue Injury in Athletes, Oral H2Consumption + Topical**
Ostojic, S. M., Vukomanovic, B., Calleja-Gonzalez, J., & Hoffman, J. R. (2015). Effectiveness of oral and topical hydrogen for sports-related soft tissue injuries. Postgraduate Medicine, 126(5).

11. Responses to Exercise, Hydrogen Water
Botek, M., Krejci, J., McKune, A., & Sládečková, B. (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, T., Gando, Y., Takahashi, M., Hara, R., Suzuki, K., & Muraoka, I.  (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, P., Stojanovic, M. D.M., Trivic, T., & Ostojic, S. M. (2016). Molecular hydrogen affected post-exercise recovery in judo athletes. Medicine & Science in Sports & Exercise, 48(5S): 1071

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, J. & Stajer, V. 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, S. M. (2019). Short-term H2 inhalation improves exercise performance in healthy adults. Biology of Sport, 36(4): 333–339. 

19. Acute Ingestion for Exercise Performance, Hydrogen Water No Results
Ooi, C. H., Ng, S. K., & Omar, E. A. (2019). Acute ingestion of hydrogen-rich water does not improve incremental treadmill running performance in endurance-trained athletes. Applied Physiology and Research Metabolism, 45(5)

20. Physical Activity of Athletes, Hydrogen Water
Wu, P. (2020). Hydrogen-rich water improves the physical ability of football players and the anti-fatigue ability of rats, Revista Cientifica, 30(1): 428-435.

21. Acute Hydrogen Water In Endurance Athletes, Hydrogen Water, Very Small Benefit
Ito, H., Kabayma, S., & Goto, K. (2020).Ito, H., Kabayma, S., & Goto, K. (2020).Effects of electrolyzed hydrogen water ingestion during endurance exercise in a heated environment on body fluid balance and exercise performance. Temperature, 7(3): 290–299.

22. Topical Hydrogen Water vs. RICE Protocol for Ankle Tears, Hydrogen Water OUR HYDROGEN TABLETS
Javorac, D., Stajer, V., Ratgeber, L., Olah, A., Betlehem, J., Acs, P., Vukomanovic, B., & Ostojic, S. M. (2020). Hydrotherapy with hydrogen-rich water compared with RICE protocol following acute ankle sprain in professional athletes: a randomized non-inferiority pilot trial. Research in Sports Medicine, 1–9.

23. Exercise Recovery and Exercise Performance, Hydrogen Inhalation
Shibayama, Y., Dobashi, S., Fukuoka, T., Arisawa, T., Koyama, K. (2020). The effects of rich hydrogen and oxygen mixed gas inhalation after high intensity exercise influence on exercise performance. Medicine & Science in Sports & Exercise, 52(7S): 1024–1025.

24. Muscular Damage and Soreness, Hydrogen Water Bath
Todorovic, N. Javorac, D., Stajer, V., & Ostojic, S. M. (2020). 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.

25. Acute Use for Exercise Performance-Hydrogen Water, Unclear Results
Botek, M., Krejčí, J., McKune, A. J., & Sládečková, B. Hydrogen-rich water supplementation and up-hill running performance: Effect of athlete performance level. International Journal of Sports Physiology and Performance, 15(8): 1193–1196

26. Hydrogen Water Decreased Lactic Acid and Lactate Dehydrogenase Following Resistance Training, Hydrogen Water.
Moradi, B., Saberi, E., Hasani, & A., Saheb, A. M. 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
Shibayama, Y., Dobashi, S., Arisawa, T., Fukuoka, T., & Koyama, K. (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. Medical Gas Research, 10(4): 155162.

28. Hydrogen Creating Capsules on Ventilatory and Ergogenic Adjustments During Exercise, Hydrogen Creating Capsules
Alharbi, A. A. D., Ebine, N., Nakae, S., Hojo, T., & Fukuoka, Y. (2020). Application of molecular hydrogen as an antioxidant in responses to ventilatory and ergogenic adjustments during incremental exercise in humans. Nutrients, 13(2): 459

29. Acute Injury Recovery, Hydrogen-Rich Hydrotherapy
Alex Tarnava, A. (2021). Supersaturated hydrogen-rich water hydrotherapy for recovery of acute injury to the proximal phalanges on the 5th toe: a case report. Journal of Science and Medicine, 3(1)

30. Physical Performance of Trained and Untrained Subjects, Hydrogen Water
Timón, R., Olcina, G., González-Custodio, A., Camacho-Cardenosa, M., Camacho-Cardenosa, A., & Martínez Guardado, I. (2021). Effects of 7-day intake of hydrogen-rich water on physical performance of trained and untrained subjects. Biology of Sport 38(2): 269–275

31. Muscle Performance and Oxidative Stress After Severe Exercise, Hydrogen Water
Dobashi, S., Takeuchi, K., & Koyama, K. (2020). Hydrogen-rich water suppresses the reduction in blood total antioxidant capacity induced by 3 consecutive days of severe exercise in physically active males. Medical Gas Research, 10(1): 21–26

32. Increased Peak Oxygen Uptake During Incremental Cycling Exercise, Hydrogen Water
Hori, A., Sobue, S., Kurokawa, R., Hirano, S.-I., 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.  Medical Gas Research, 10(4): 163–169.

33. Muscle Performance, Hydrogen WaterBotek, M., Krejci, J., Mckune, A. J., Valenta, M., & Sládečková, B. (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,

34. Ventilatory and Ergogenic Adjustments During Incremental Exercise, H2 – Rich Calcium Powder
Alharbi, A. A. D., Ebine, N., Nakae, S., Hojo, T., & Fukuoka, Y. (2021). Application of Molecular Hydrogen as an Antioxidant in Responses to Ventilatory and Ergogenic Adjustments during Incremental Exercise in Humans. Nutrients, 13(2): 459.

35. Facilitation of Lipid Metabolism During Aerobic Exercise, Hydrogen Inhalation

Hori, A., Kimura, H., Kondo, T., Ichihara, M., Ogata, H., Hotto, N. (2020). Inhalation of molecular hydrogen increases breath acetone excretion during submaximal exercise: a randomized, single-blinded, placebo-controlled study. Medical Gas Research, (10)3

36. Exercise and Cognitive Performance, H2-Infused Beverage

LeBaron T., Kharman J., McCullough M. (2021). Effects of an H2-infused, Nitric Oxide-Producing Functional Beverage on Exercise and Cognitive Performance. Journal of Science and Medicine; 3(2):1-15

37. Effects of pre-exercise H2 inhalation on physical fatigue and related prefrontal cortex activation

Hong Y, Dong G, Li Q, Wang V, Liu M, Jiang G, Bao D and Zhou J (2022) Effects of pre-exercise H2 inhalation on physical fatigue and related prefrontal cortex activation during and after high-intensity exercise. Front. Physiol. 13:988028.

38. Hydrogen Rich Water Consumption Positively Affects Muscle Performance

Botek, Michal1; Krejčí, Jakub1; McKune, Andrew2,3; Valenta, Michal1; Sládečková, Barbora1. 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: October 2022 – Volume 36 – Issue 10 – p 2792-2799
doi: 10.1519/JSC.0000000000003979

39. Short-Term Consumption of Hydrogen-Rich Water Enhances Power Performance and Heart Rate Recovery

Dong G, Fu J, Bao D, Zhou J. Short-Term Consumption of Hydrogen-Rich Water Enhances Power Performance and Heart Rate Recovery in Dragon Boat Athletes: Evidence from a Pilot Study. International Journal of Environmental Research and Public Health. 2022; 19(9):5413.

40. Effects of Intestinal Bacterial Hydrogen Gas Production on Muscle Recovery following Intense Exercise in Adult Men

Eda, N.; Tsuno, S.; Nakamura, N.; Sone, R.; Akama, T.; Matsumoto, M. Effects of Intestinal Bacterial Hydrogen Gas Production on Muscle Recovery following Intense Exercise in Adult Men: A Pilot Study. Nutrients 2022, 14, 4875.

There are currently 17 publications exploring various neurological outcomes from hydrogen therapy in humans. Regarding hydrogen therapy and the brain, the methods are more spread out, with seven of the 16 studies involving hydrogen water (although one did not find a benefit), six of the studies using hydrogen inhalation (although two did not find a benefit), two of the studies using hydrogen-rich saline, one using intravenous hydrogen therapy and one using H2-infused, nitric oxide-producing functional beverage.

1. Mild Cognitive Impairment, Hydrogen Water

Nishimaki, K., Asada, T., Ohsawa, I., Nakajima, E., Ikejima, C., Yokota, T., Kamimura, N., & Ohta, S. (2018). Effects of molecular hydrogen assessed by an animal model and a randomized clinical study on mild cognitive impairment. Current Alzheimer Research., 15(5): 482–492.

2. Improving Outcomes of Alzheimer’s, Hydrogen Inhalation

Ono, H., Nishijima, Y., Sakamoto, M., Horikosi, T., Tamaki, M., Oishi, W., Naitoh, Y., Futaki, T., Ishii, S., Suzuki, K., Kurihara H., & Ohta, S. (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. International Journal of Alzheimers & Neurological Disorders, 1(1): 004.

3. Acute Cerebral Infarction, Hydrogen Inhalation

Ono, H., Nishijima, Y., Ohta, S., Sakamoto, M., Kinone, K., Horikosi, T., Tamaki, M., Takeshita, H., Futatuki, T., Ohishi, W., Ishiguro, T., Okamoto, S., Ihsii, S., & Takanami, H. (2017). Hydrogen gas inhalation treatment in acute cerebral infarction: A randomized controlled clinical study on safety and neuroprotection. Journal of Stroke & Cerebrovascular Diseases, 26(11): 2587–2594.

4. Acute Cerebral Ischemia, Hydrogen Inhalation

Ono, H., Nishijima, Y., Adachi, N., Sakamoto, M., Kudo, Y., Kaneko, K., Nakao, A., & Imaoka, T. (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, 9(21).

5. Acute Brain Stem Infarct, Hydrogen Saline + Edaravone

Ono, H., Nishijima, Y., Adachi, N., Tachibana, S., Chitoku, S., Mukaihara, S., Sakamoto, M., Kudo, Y., Nakazawa, J., Kanedo, K., & Nawashiro, H. (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, 1(12).

6. Acute Cerebral Infarction, Hydrogen Saline + Edaravone

Nagatani, K., Nawashiro, H., Takeuchi, S., Tomura, S., Otani, N., Osada, H., Wada, K., Katch, H., Tsuzuki, N., & Mori, K. (2013). Safety of intravenous administration of hydrogen-enriched fluid in patients with acute cerebral ischemia: initial clinical studies. Medical Gas Research, 3: 13. 

7. Newborn Abnormal Neurological Function, Hydrogen Water

Yang, L, Li, D., & Chen, S. (2016). Hydrogen water reduces NSE, IL-6, and TNF-α levels in hypoxic-ischemic encephalopathy. Open Medicine, 11(1): 399–406.

8. Parkinson’s, Hydrogen Water

Yoritaka, A., Takanashi, M., Hirayama, M., Nakahara, T., Ohta, S., & Hattori, N.  (2013). Pilot study of H₂ therapy in parkinson’s disease: a randomized double-blind placebo-controlled trial. Movement Disorders, 28(6): 836–9.

9. Parkinson’s Disease, No Result, Hydrogen Water****

Yoritaka et al., (2018). Randomized, double-blind, multicenter trial of hydrogen water for Parkinson’s disease. Movement Disorders.

****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 paper. The exact routine is unknown. There is currently underway a 52-week, 70-participant trial on Parkinson’s Disease 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.

10. Parkinson’s Disease, No Result, Hydrogen Inhalation

Hirayama, M., Ito, M., Minato, T., Yoritaka, A., LeBaron, T. W., & Ohno, K. (2018). Inhalation of hydrogen gas elevates urinary 8-hydroxy-2′-deoxyguanine in Parkinson’s disease. Medical Gas Research, 8(4): 144–149.

11. Concussion Recovery Case Study, Hydrogen Water OUR HYDROGEN TABLETS

Javorac, D., Stajer, V., & Ostojic, S. M. (2019). Case Report: Buccal Administration of Hydrogen-Producing Blend After a Mild Traumatic Brain Injury in a Professional Athlete. [version 1; peer review: 2].F1000 Research, 8: 1024.

12. Cognitive Function in Elderly, Hydrogen Inhalation

Korovljev, D., Trivic, T., Stajer, V., Drid, P., Sato, B., & Ostojic, S. M. (2019). Short-term H2 inhalation improves cognitive function in older women: A pilot study. International Journal of Gerontology, 14 (2): 149–150.

13. Hydrogen Water vs. Caffeine for Improving Alertness After Sleep Deprivation, Hydrogen Water OUR HYDROGEN WATER TABLETS

Zanini, D., Stajer, V., & Ostojic, S. M. (2020). Hydrogen vs. caffeine for improved alertness in sleep-deprived humans. Neurophysiology 52, 67–72.

14. Photobiomodulation on Parkinson Disease, Hydrogen Water

Hong, C.-T., Hu, C. J., Lin, H.-Y., & Wu, D. (2021). Effects of concomitant use of hydrogen water and photobiomodulation on Parkinson disease: A pilot study. Medicine (Baltimore), 100(4): e24191.

15. Subarachnoid Hemorrhage, Intravenous Hydrogen Therapy

Takeuchi, S., Kumagai, K., Toyooka, T., Otani, N., Wada, K., & Mori, K. (2021). Intravenous Hydrogen Therapy With Intracisternal Magnesium Sulfate Infusion in Severe Aneurysmal Subarachnoid Hemorrhage. Stroke, 52(1), 20–27. 

16. Parkinson’s Disease, No Result, Hydrogen Inhalation

Yoritaka, A., Kobayashi, Y., Hayashi, T., Saiki S., Hattori, N. (2021). Randomized double-blind placebo-controlled trial of hydrogen inhalation for Parkinson’s disease: a pilot study. Neurological Sciences

17. Neuroprotective Agent for TBIs and Concussions, An H2-Infused, Nitric Oxide-Producing Beverage

LeBaron, W. T., Kharman, J., McCullough, L. Michael. (2021). An H2-infused, nitric oxide-producing functional beverage as a neuroprotective agent for TBIs and concussions. Journal of Integrative Neuroscience, 20(3).

Skin

There are currently 12 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, Q., Wu, Y., Li, Y, Chen. Z., Wang, L., Xiong, H., Dai, E., Wu, J., Fan, B., Ping, L., Luo, X. (2018).  Positive effects of hydrogen-water bathing in patients of psoriasis and parapsoriasis en plaques. Sci Rep 8, 8051.

2. Wrinkles Reduction, Hydrogen Water Baths

Kato, S., Saitoh, Y., Iwai, K., & Miwa, N. (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, 106, 24–33.

3. Red Skin/Inflamed Diseases, Hydrogen Saline

Ono, H., Nishijima, Y., Adachi, N., Sakamoto, M., Kudo, Y., Nakazawa, J., Kaneko, K., & Nakao, A. (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, 2(1): 14.

4. Psoriasis, Skin Lesions, Case Studies, Hydrogen Water+Saline+Gas

Ishibashi, T., Ichikawa, M., Sato, B., Shibata, S., Hara, Y., Naritomi, Y., Okazaki, K., Nakashima, Y., Iwamoto, Y., Koyanagi, S., Hara, H., & Nagao, T. (2015). Improvement of psoriasis-associated arthritis and skin lesions by treatment with molecular hydrogen: A report of three cases. Molecular Medicine Reports, 12(2): 2757–64.

5. Pressure Ulcers, Hydrogen Water

Li, Q., Kato, S., Matsuoka, D., Tanaka, H., & Miwa, N. (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, 3(1): 20.

6. Graft vs. Host Disease Case Study, Hydrogen Water (Drinking)

Qian, L.-R., & Shen, J.-L. (2016). Successful treatment with hydrogen rich water in a case of chronic graft-versus-host-disease. Medical Gas Research, 6(3): 177–179.

7. UV Damage in Skin in Vivo, Topical Hydrogen Water

Shin, M. H., Park, R., Nojima, H., Kim, H.-C., Kim, Y. K., & Chung, J. H. (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(4): e61696.

8. Keratin Plugged Hair Pores, Hydrogen Water Baths

Tanaka, Y., Saitoh, Y., & Miwa, N. (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, 8(1): 12–18.

9. Visceral Fat and Skin Blotches, Hydrogen Water Baths

Asada, R., Saitoh, Y., & Miwa, N. (2019). Effects of hydrogen-rich water bath on visceral fat and skin blotch, with boiling-resistant hydrogen bubbles. Medical Gas Research, 9(2): 68–73.

10. Skin Aging and Antioxidant Activity, Hydrogen Water Mask

Kwon, H.-J., Han, S.-B., & Park, K.-W. (2020). Antioxidant activity of hydrogen water mask pack composed of gel-type emulsion and hydrogen generation powder. International Journal of Molecular Sciences, 21(24): 9731.

11. Heat Retention Effects, Hydrogen Baths

Kato, S., Takada, Y., & Miwa, N. (2021). Heat-retention effects of hydrogen-rich water bath assessed by thermography for humans. Journal of Thermal Biology, 95: 102805.

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.

13. Hydrogen-Rich Water Improve Wrinkles and Blotches

Yoshiharu T. Nobuhiko M.  (2022) Repetitive Bathing and Skin Poultice with Hydrogen-Rich Water Improve Wrinkles and Blotches Together with Modulation of Skin Oiliness and Moisture, 3(2):161-178.

14. Hydrogen-rich bath with nano-sized bubbles improves antioxidant capacity

Tanaka Y, Xiao L, Miwa N. Hydrogen-rich bath with nano-sized bubbles improves antioxidant capacity based on oxygen radical absorbing and inflammation levels in human serum. Med Gas Res 2022;12:91-9

15. Repetitive Bathing and Skin Poultice with Hydrogen-Rich Water Improve Wrinkles and Blotches

Tanaka Y, Miwa N. Repetitive Bathing and Skin Poultice with Hydrogen-Rich Water Improve Wrinkles and Blotches Together with Modulation of Skin Oiliness and Moisture. Hydrogen. 2022; 3(2):161-178.

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, H., Hayashi, Y., Zhu, W.-J., Matsuyama, Y., Terada, T., Kabayama, S., Watanabe, T., Era, S., Sato, B., & Nakayama, M. (2013). Transperitoneal administration of dissolved hydrogen for peritoneal dialysis patients: a novel approach to suppress oxidative stress in the peritoneal cavity. Medical Gas Research, 3, Article 14.

2. Kidney Dialysis for Inflammation, Hydrogen Saline

Nakayama, M., Nakano, H., Hamada, H., Itami, N., Nakazawa, R., & Ito, S. (2010). A novel bioactive haemodialysis system using dissolved dihydrogen (H2) produced by water electrolysis: A clinical trial. Nephrology Dialysis Transplantation, 25(9): 3026–3033.

3. Low Hydrogen Dialysis

Nakayama, M., Kabayama, S., Nakano, H., Zhu, W.-J., 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.

4. Improvement in Chronic Dialysis Patients, Hydrogen Rich Dialysis

Nakayama, M., Itami, N., Suzuki, H., Hamada, H., Yamamoto, R., Tsunoda, K., Osaka, N., Nakano, H., Maruyama, Y., Kabayama, S., Nakazawa, R., Miyazaki, M., & Ito, S. (2018). Novel haemodialysis (HD) treatment employing molecular hydrogen (H2)-enriched dialysis solution improves prognosis of chronic dialysis patients: A prospective observational study. Scientific Reports, 8, Article 254.

5. Improvement of the Fraction of Human Mercaptalbumin on Hemodialysis Treatment, Hydrogen Rich Dialysis

Maeda, K., Yoshizaki, S., Iida, T., Terada, T., Era, S., Sakashita, K., & Arikawa, H. (2016). Improvement of the fraction of human mercaptalbumin on hemodialysis treatment using hydrogen-dissolved hemodialysis fluid: A prospective observational study. Renal Replacement Therapy, 2, Article 42.

6. Interim Analysis, Observational Improvements Over 12 Months in 262 Patients on Dialysis, Hydrogen Rich Dialysis

Nakayama, M., Itami, N., Suzuki, H., Hamada, H., Osaka, N., Yamamoto, R., Tsunoda, K., Nakano, H., Watanabe, K., Zhu, W.-J., Maruyama, Y., Terawaki, H., Kabayama, S., Nakazawa, R., Miyazaki, M., & Ito, S. (2017). Possible clinical effects of molecular hydrogen (H2) delivery during hemodialysis in chronic dialysis patients: Interim analysis in a 12 month observation. PLOS One, 12(9): e0184535.

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, K.-M., Kang, Y.-N., Choi, I.-B., Gu, Y., Kawamura, T., Toyoda, Y., & Nakao, A.  (2011). Effects of drinking hydrogen-rich water on the quality of life of patients treated with radiotherapy for liver tumors. Medical Gas Research, 1(1): 11.

2. Improved Liver Function on Patients on Chemotherapy, Hydrogen Water

Yang, Q., Ji, G., Pan, R., Zhao, Y., & Yan, P. (2017). Protective effect of hydrogen-rich water on liver function of colorectal cancer patients treated with mFOLFOX6 chemotherapy. Molecular and Clinical Oncology, 7(5): 891–896.

Cancer

There are currently six 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, J., & Baba, H. (2019). Hydrogen gas restores exhausted CD8+ T cells in patients with advanced colorectal cancer to improve prognosis. Oncology Reports, 41(1): 301–311.

2. Stage III and Stage IV Cancer, Cohort, Hydrogen Inhalation

Chen, J.-B., Kong, X.-F., Lv, Y.-Y., Qin, S.-C., Sun, X.-J., Mu, F., Lu, T.-Y., & Xu, K.-C. (2019). “Real world survey” of hydrogen-controlled cancer: A follow-up report of 82 advanced cancer patients. Medical Gas Research, 9(3): 115–121.

3. Case Study Gallbladder Cancer, Hydrogen Inhalation

Chen, J.-B., Mu, F., Lu, T., Ma, Y., Du, D., & Xu, K. (2019). A gallbladder carcinoma patient with pseudo-progressive remission after hydrogen inhalation. OncoTargets and Therapy, 12, 8645–8651.

Chen, J.-B., Pan, Z.-B., Du, D.-M., Qian, W., Ma, Y.-Y., Mu, F., & Xu, K.-C. (2019). Hydrogen gas therapy induced shrinkage of metastatic gallbladder cancer: A case report. World Journal of Clinical Cases, 7(15): 2065–2074.

4. Bone Marrow, Hydrogen Inhalation

Hirano, S.-I., Aoki, Y., Kurokawa, R., Li, X.-K., Ichimaru, N., Takahara, S., & Takefuji, Y. Protective effect of hydrogen gas inhalation on radiation-induced bone marrow damage in cancer patients: a retrospective observational study.

5. Lung Cancer, Hydrogen Gas

Akagi, J., & Baba, H. (2020). 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. Spandidos Publications, Article 258.

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.

Other

There are 28 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. Fifteen of these 25 trials used hydrogen water as the delivery method, although one did not find a statistically significant result but did note a potential responder group. Nine trials used hydrogen inhalation.

1. Hepatitis B, Hydrogen Water

Xia, C., Liu, W., Zeng, D., Zhu, L., Sun, X., & Sun, X. (2013). Effect of hydrogen-rich water on oxidative stress, liver function, and viral load in patients with chronic hepatitis B. Clinical and Translational Science, 6(5): 372–5.

2. Post-Cardiac Arrest, Hydrogen Inhalation

Tamura, T., Hayashida, K., Sano, M., Suzuki, M., Shibusawa, T., Yoshizawa, J., Kobayashi, Y., Suzuki, T., Ohta, S., Morisaki, H., Fukuda, K., & Hori, S. (2016). Feasibility and safety of hydrogen gas inhalation for post-cardiac arrest syndrome – First-in-human pilot study. Circulation Journal, 80(8): 1870–1873.

3. Heart Surgery, Hydrogen Inhalation

Katsumata, Y., Sano, F., Abe, T., Tamura, T., Fujisawa, T., Shiraishi, Y., Kohsaka, S., Ueda, I., Homma, K., Suzuki, M., Okuda, S., Maekawa, Y., Kobayashi, E., Hori, S., Sasaki, J., Fukuda, K., & Sano, M. (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. Circulation Journal, 81(7): 940–947.

4. Hydrogen-Rich Water for Improvements of Mood, Anxiety and Autonomic Nerve Function in Daily Life, Hydrogen Water

Mizuno, K., Sasaki, A. T., Ebisu, K., Tajima, K., Kajimoto, O., Nojima, J., Kuratsune, H., Hori, H., & Watanabe, Y. (2017). Hydrogen-rich water for improvements of mood, anxiety, and autonomic nerve function in daily life. Medical Gas Research, 7(4): 247–255.

5. Periodontitis and Antioxidant Status, Hydrogen Water

Azuma, T., Yamane, M., Ekuni, D., Kawabata, Y., Kataoka, K., Kasuyama, K., Maruyama, T., Tomofuji, T., & Morita, M. (2015). Drinking hydrogen-rich water has additive effects on non-surgical periodontal treatment of improving periodontitis: A pilot study. Antioxidants, 4(3): 513–522.

6. Blood Alkalization, Hydrogen Water

Ostojic, S. M. (2012). Serum alkalinization and hydrogen-rich water in healthy men. Mayo Clinic Proceedings, 87(5): 501–502.

7. Blood Alkalization, Hydrogen Water

Ostojic, S. M., & Stojanovic, M. D. (2012). Hydrogen-rich water affected blood alkalinity in physically active men. Research in Sports Medicine, 22(1): 49–60.

8. Painful Bladder Syndrome, Hydrogen Water (Did Not Work, Potential Small Responder Group)

Matsumoto, S., Ueda, T., & Kakizaki, H. (2013). Effect of supplementation with hydrogen-rich water in patients with interstitial cystitis/painful bladder syndrome. Urology, 81(2): 226–230.

9. Fecal Matter and Reported Sleep Function, Hydrogen Water

Tanaka, Y., Saihara, Y., Izumotani, K., & Nakamura, H. (2018). Daily ingestion of alkaline electrolyzed water containing hydrogen influences human health, including gastrointestinal symptoms. Medical Gas Research, 8(4): 160–166.

10. Tracheal Stenosis (Cause Not Stated, Radiation Therapy?), Hydrogen Inhalation

Zhou, Z.-Q., Zhong, C.-H., Su, Z.-Q., Li, X.-Y., Chen, Y., Chen, X.-B., Tang, C.-L., Zhou, L.-Q., & Li, S.-Y. (2019). Breathing hydrogen-oxygen mixture decreases inspiratory effort in patients with tracheal stenosis. Respiration, 97(1): 42–51.

11. Gastroesophageal Reflux Disease (GERD), Hydrogen-Rich Water

Franceschelli, S., Gatta, D. M. P., Pesce, M., Ferrone, A., Di Martino, G., Di Nicola, M., De Lutiis, M. A., 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, 22(5): 2750–2759.

12. Inflammation and Apoptosis Reduction in Healthy Individuals, Hydrogen Water

Sim, M., Kim, C.-S., Shon, W.-J., Lee, Y.-K., Choi, E. Y., & Shin, D.-M. (2020). Hydrogen-rich water reduces inflammatory responses and prevents apoptosis of peripheral blood cells in healthy adults: A randomized, double-blind, controlled trial. Scientific Reports 10, Article 12130.

13. Disease Severity and Dyspnea in COVID-19 Patients, Hydrogen Inhalation

Guan, W.-J., Wei, C.-H., Chen, A.-L., Sun, X.-C., Guo, G.-Y., Zou, X., Shi, J.-D., Lai, P.-Z., Zheng, Z.-G., & Zhong, N.-S. (2020). 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, L., Liu, M., Shen, J., Cen, J., & Zhao, D. (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. (2020). [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, 34(3): 244–247.

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. (2019). Effects of hydrogen in prevention of corneal endothelial damage during phacoemulsification: A prospective randomized clinical trial. American Journal of Ophthalmology, 207, 10–17.

17. Prevention of Dry Eye Disease, Hydrogen H2-Producing Milk

Kawashima, M., Tsuno, S., Matsumoto, M., & Tsubota, K. (2019). Hydrogen-producing milk to prevent reduction in tear stability in persons using visual display terminals. The Ocular Surface,17(4): 714–721.

18. Immune Function of Middle-Aged Participants, Hydrogen Inhalation

Chen, J.-B., Kong, X.-F., & 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.

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.

21. Increased Sympathetic Cardiac Activity in Healthy Females, Hydrogen Water

Botek, M., Sládečková, B., Krejčí, J., Pluháček, F., Najmanová, E. (2021). Acute hydrogen-rich water ingestion stimulates cardiac autonomic activity in healthy females. Acta Gymnica, 51, Article e2021.009.

22. Malignant Neuropathic Pain, Hydrogen Water

Li, D. Yan, M. (2016). Clinical assessment of hydrogen-rich water and oxycodone hydrochloride controlled-release tablets in the treatment of malignant neuropathic pain. Journal of Chinese Physician, 18(9):1329-1331,1335

23. Dry Eye Disease, H2-Generating Supplement

Kubota, M. Kawashima, M, Inoue, S., Imada, T., Nakamura, S., Kubota, S., Watanabe, M, Takemura, R., Tsubota, K. (2021). Randomized, crossover clinical efficacy trial in humans and mice on tear secretion promotion and lacrimal gland protection by molecular hydrogen. Scientific Reports 11, Article 6434

24. Chronic Obstructive Pulmonary Disease, Hydrogen Inhalation

Zheng, ZG., Sun, WZ., Hu, J.Y., Jie, ZJ., Xu, JF., Cao, J., Song, YL., Wang, CH., Wang, J., Zhao, H., Guo, ZL., Zhong, NS. (2021). Hydrogen/oxygen therapy for the treatment of an acute exacerbation of chronic obstructive pulmonary disease: results of a multicenter, randomized, double-blind, parallel-group controlled trial. Respiratory Research, 22, 149

25. Effects on biomarkers of aging in older adults, OUR HYDROGEN TABLETS

Zanini, D., Todorovic, N., Korovljev, D., Stajer, V., Ostojic, J., Purac, J., Kojic, D., Vukasinovic, E., Djordjievski, S., Sopic, M., Guzonjic, A., Ninic, A., Erceg, S., Ostojic, S.M. (2021). 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. Experimental Gerontology, 155

26. Stool Consistency and Gut Microbiota, Hydrogen-Dissolved Alkaline Electrolyzed Water

Tanaka, Y., Kiuchi, M., Higashimura, Y., Naito, Y., & Koyama, K. (2021). The effects of ingestion of hydrogen-dissolved alkaline electrolyzed water on stool consistency and gut microbiota: a double-blind randomized trial. Medical Gas Research, 11,4

27. Covid-19, OUR HYDROGEN TABLETS

Singh, RB., Halabi, G., Fatima, G., Rai, RH., Tarnava, AT., LeBaron, TW. (2021). Molecular hydrogen as an adjuvant therapy may be associated with increased oxygen saturation and improved exercise tolerance in a COVID-19 patient. Clin Case Rep., 9:e05039

28. Post Acute Covid-19 Patients Suffering CFS, Hydrogen Inhalation

Shogenova, L., Truong, T., Kryukova, N. & Yusupkhodzhaeva, K. & Pozdnyakova, D. & Kim, T. & Chernyak, A. & Kalmanova, Е & Medvedev, O. & Kuropatkina, T. & Varfolomeev, S. & Ryabokon, A. & Svitich, O. & Kostinov, M. & Kunio, Ibaraki & Hiroki, Maehara & Chuchalin, A.. (2021). Hydrogen inhalation in rehabilitation program of the medical staff recovered from COVID-19. Cardiovascular Therapy and Prevention, 20(6): 2986.

29. Hydrogen Intake Relieves Alcohol Consumption and Hangover Symptoms in Healthy Adults: a Randomized and Placebo-Controlled Crossover Study

Lv X, Lu Y, Ding G, et al. Hydrogen Intake Relieves Alcohol Consumption and Hangover Symptoms in Healthy Adults: a Randomized and Placebo-Controlled Crossover Study [published online ahead of print, 2022 Sep 16]. Am J Clin Nutr. 2022;nqac261. doi:10.1093/ajcn/nqac261

30. A double-blinded, randomized controlled clinical trial of hydrogen inhalation therapy for idiopathic sudden sensorineural hearing loss

Okada M, Ogawa H, Takagi T, Nishihara E, Yoshida T, Hyodo J, Shinomori Y, Honda N, Fujiwara T, Teraoka M, Yamada H, Hirano S-i and Hato N (2022) A double-blinded, randomized controlled clinical trial of hydrogen inhalation therapy for idiopathic sudden sensorineural hearing loss. Front. Neurosci. 16:1024634. doi: 10.3389/fnins.2022.1024634

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.

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, 52(6): 817–820.

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.

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.

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.

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. Nephrology Dialysis, Transplantation, 25(8) 2730–7.

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, 5(3): 83–89.

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.

11. Electrolyzed Water, Type 2 Diabetes

Rias, Y. A., Kurniawan, A. L., Chang, 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.

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.

1. 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.

2. Lee, K.J., et al., (2004). 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.

3. 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.

4. 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] 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.

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.

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, K., 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.

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.

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, X., 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.

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.

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. (2013). Evaluation of stability changes in magnesium-incorporated titanium implants in the early healing period. The Journal of Craniofacial Surgery, 24(5), 1552–7.

7. Biodegradable Magnesium-Based Screw in Hallux Valgus Surgery

Windhagen, H., Radtke, K., Weizbauer, A., Diekmann, J., Noll, Y., Kreimeyer, U., Schavan, R., Stukenborg-Colsman, C., & Waizy, H. (2013). Biodegradable magnesium-based screw clinically equivalent to titanium screw in hallux valgus surgery: Short term results of the first prospective, randomized, controlled clinical pilot study. Biomedical Engineering Online, 12, 62.

8. Magnesium-Enriched Hydroxyapatite and Angiogenesis-Osteogenesis Interplay

Canullo, L., Heinemann, F., Gedrange, T., Biffar, R., & Kunert-Keil, C. (2013). Histological evaluation at different times after augmentation of extraction sites grafted with a magnesium-enriched hydroxyapatite: Double-blinded randomized controlled trial. Clinical Oral Implants Research, 24(4) 398–406.

9. Bioabsorbable Magnesium Coronary Stents

Erbel, R., Di Mario, C., Bartunek, J., Bonnier, J., de Bruyne, B., Eberli, F. R., Erne, P., Haude, M., Heublein, B., Horrigan, M., Ilsley, C., Böse, D., Koolen, J., Lüscher, T. F., Weissman, N., & Waksman, R. (2007). Temporary scaffolding of coronary arteries with bioabsorbable magnesium stents: A prospective, non-randomised multicentre trial. Lancet, 369(9576), 1869–1875.

A Sampling of the Many Review Articles

Metabolic and Cardiac

1. LeBaron, T. W., Kura, B., Kalocayova, B., Tribulova, N., & Slezák, J. (2019). A new approach for the prevention and treatment of cardiovascular disorders. molecular hydrogen significantly reduces the effects of oxidative stress. Molecules, 24(11): 2076.

2. Zhang, Y., Tan, S., Xu, J., & Wang, T. (2018). Hydrogen therapy in cardiovascular and metabolic diseases: From bench to bedside. Cellular Physiology and Biochemistry, 47, 1–10.

Alzheimer’s and Neurological Conditions

1. Tan, X., Shen, F., Dong, W.-L., Yang, Y., & Chen, G. (2018). The role of hydrogen in Alzheimer’s disease. Medical Gas Research, 8(4): 176–180.

2. Ono, H., Nishijima, Y., Sakamoto, M., Horikosi, T., Tamaki, M., Oishi, W., Naitoh, Y., Futaki, T., Ishii, S., Suzuki, K., Kurihara H., & Ohta, S. (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. International Journal of Alzheimers & Neurological Disorders, 1(1): 004.

3. Dohi, K., Satoh, K., Miyamoto, K., Momma, S., Fukuda, K., Higuchi, R., Ohtaki, H., & Banks, W. A. (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, 61(1): 1–5.

4. Iketani, M. & Ohsawa, I. (2017). Molecular hydrogen as a neuroprotective agent. Current Neuropharmacology, 15(2): 324–331.

Exercise Performance

1. LeBaron, T. W., Laher, I., Kura, B., & Slezák, J. (2019). Hydrogen gas: from clinical medicine to an emerging ergogenic molecule for sports athletes.Canadian Journal of Physiology and Pharmacology, 97(9).

Radiation Injury

1. Kura, B., Bagchi, A. K., Singal, P. K., Barancik, M., LeBaron, T. W., Valachova, K., Šoltés, L., & Slezák, J. (2018). Molecular hydrogen: potential in mitigating oxidative-stress-induced radiation injury.Canadian Journal of Physiology and Pharmacology, 97(4).

Sepsis

1. Qiu, P., Liu, Y., & Zhang, J. (2019). Recent advances in studies of molecular hydrogen against sepsis.International Journal of Biological Sciences, 15(6): 1261–1275.

Emergency and Critical Care

1. Sano, M., Suzuki, M., Homma, K., Hayashida, K., Tamura, T., Matsuoka, T., Katsumata, Y., Onuki, S., & Sasaki, J. (2017). Promising novel therapy with hydrogen gas for emergency and critical care medicine. Acute Medicine & Surgery.

2. Yang, M., Zhang, Z., Gao, B., Liu, L., & Hu, T. (2017). Hydrogen medicine therapy: an effective and promising novel treatment for multiple organ dysfunction (MODS) induced by infuenza and other viral infections diseases? SOJ Microbiology & Infectious Diseases, 5(2): 1–6.

General Reviews

1. Ichihara, M., Sobue, S., Ito, M., Ito, M., Hirayama, M., & Ohno, K. (2015). Beneficial biological effects and the underlying mechanisms of molecular hydrogen — Comprehensive review of 321 original articles.Medical Gas Research, 5: 12.

2. Dixon, B. J., Tang, J., & Zhang, J. H. (2013). The evolution of molecular hydrogen: A noteworthy potential therapy with clinical significance. Medical Gas Research, 3(1): 10.

3. Nicolson, G. L., Ferreira de Mattos, G., Settineri, R., Costa, C., Ellithorpe, R., Rosenblatt, S., La Valle, J., Jimenez, A., & Ohta, S. (2016). Clinical effects of hydrogen administration: From animal and human diseases to exercise medicine.International Journal of Clinical Medicine, 7(1).

4. Li, H.-M., Shen, L., Ge, J.-W., & Zhang, R.-F. (2018). The transfer of hydrogen from inert gas to therapeutic gas.Medical Gas Research, 7(4): 265–272

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