Int J Sports Med 2015; 36(04): 273-279
DOI: 10.1055/s-0034-1395509
© Georg Thieme Verlag KG Stuttgart · New York

Molecular Hydrogen in Sports Medicine: New Therapeutic Perspectives

S. M. Ostojic
1   Center for Health, Exercise and Sport Sciences, Exercise Physiology Lab, Belgrade, Serbia
› Author Affiliations
Further Information

Publication History

accepted after revision 18 September 2014

Publication Date:
19 December 2014 (online)


In the past 2 decades, molecular hydrogen emerged as a novel therapeutic agent, with antioxidant, anti-inflammatory and anti-apoptotic effects demonstrated in plethora of animal disease models and human studies. Beneficial effects of molecular hydrogen in clinical environment are observed especially in oxidative stress-mediated diseases, such as diabetes mellitus, brain stem infarction, rheumatoid arthritis, or neurodegenerative diseases. A number of more recent studies have reported that molecular hydrogen affects cell signal transduction and acts as an alkalizing agent, with these newly identified mechanisms of action having the potential to widen its application in clinical medicine even further. In particular, hydrogen therapy may be an effective and specific innovative treatment for exercise-induced oxidative stress and sports injury, with potential for the improvement of exercise performance. This review will summarize recent research findings regarding the clinical aspects of molecular hydrogen use, emphasizing its application in the field of sports medicine.

  • References

  • 1 Abol-Enein H, Gheith OA, Barakat N, Nour E, Sharaf AE. Ionized alkaline water: new strategy for management of metabolic acidosis in experimental animals. Ther Apher Dial 2009; 13: 220-224
  • 2 Abraini JH, Gardette-Chauffour MC, Martinez E, Rostain JC, Lemaire C. Psychophysiological reactions in humans during an open sea dive to 500 m with a hydrogen-helium-oxygen mixture. J Appl Physiol 1994; 76: 1113-1118
  • 3 Adam S, Loertzer H, Fornara P, Brömme HJ. The carboxyproxyl-derived spin trap (CP-H) is an appropriate detector-compound for oxidative stress. Urol Res 2010; 38: 179-186
  • 4 Amaroli N, Balzani V. The hydrogen issue. ChemSusChem 2011; 4: 21-36
  • 5 Aoki K, Nakao A, Adachi T, Matsui Y, Miyakawa S. Pilot study: effects of drinking hydrogen-rich water on muscle fatigue caused by acute exercise in elite athletes. Med Gas Res 2012; 2: 12
  • 6 Buxton GV, Greenstock CL, Helman WP, Ross AB. Critical-review of rate constants for reactions of hydrated electrons, hydrogen-atoms and hydroxyl radicals (.OH/.O-) in aqueous-solution. J Phys Chem Ref Data 1988; 17: 513-886
  • 7 Cai J, Kang Z, Liu K, Liu W, Li R, Zhang JH, Luo X, Sun X. Neuroprotective effects of hydrogen saline in neonatal hypoxia-ischemia rat model. Brain Res 2009; 1256: 129-137
  • 8 Cai J, Kang Z, Liu WW, Luo X, Qiang S, Zhang JH, Ohta S, Sun X, Xu W, Tao H, Li R. Hydrogen therapy reduces apoptosis in neonatal hypoxia-ischemia rat model. Neurosci Lett 2008; 441: 167-172
  • 9 Cairns SP. Lactic acid and exercise performance: culprit or friend?. Sports Med 2006; 36: 279-291
  • 10 Chen CH, Manaenko A, Zhan Y, Liu WW, Ostrowki RP, Tang J, Zhang JH. Hydrogen gas reduced acute hyperglycemia-enhanced hemorrhagic transformation in a focal ischemia rat model. Neuroscience 2010; 169: 402-414
  • 11 Chen H, Sun YP, Hu PF, Liu WW, Xiang HG, Li Y, Yan RL, Su N, Ruan CP, Sun XJ, Wang Q. The effects of hydrogen-rich saline on the contractile and structural changes of intestine induced by ischemia-reperfusion in rats. J Surg Res 2011; 167: 316-322
  • 12 Chen X, Zuo Q, Hai Y, Sun XJ. Lactulose: an indirect antioxidant ameliorating inflammatory bowel disease by increasing hydrogen production. Med Hypotheses 2011; 76: 325-327
  • 13 Dixon BJ, Tang J, Zhang JH. The evolution of molecular hydrogen: a noteworthy potential therapy with clinical significance. Med Gas Res 2013; 3: 10
  • 14 Dole M, Wilson FR, Fife WP. Hyperbaric hydrogen therapy: a possible treatment for cancer. Science 1975; 190: 152-154
  • 15 George JF, Agarwal A. Hydrogen: another gas with therapeutic potential. Kidney Int 2010; 77: 85-87
  • 16 Gharib B, Hanna S, Abdallahi OM, Lepidi H, Gardette B, De Reggi M. Anti-inflammatory properties of molecular hydrogen: investigation on parasite-induced liver inflammation. C R Acad Sci III 2001; 324: 719-724
  • 17 Gibson GR, Macfarlane GT, Cummings JH. Sulphate reducing bacteria and hydrogen metabolism in the human large intestine. Gut 1993; 34: 437-439
  • 18 Hammer HF. Colonic hydrogen absorption: quantification of its effect on hydrogen accumulation caused by bacterial fermentation of carbohydrates. Gut 1993; 34: 818-822
  • 19 Hong Y, Chen S, Zhang JM. Hydrogen as a selective antioxidant: a review of clinical and experimental studies. J Int Med Res 2010; 38: 1893-1903
  • 20 Huang CS, Kawamura T, Toyoda Y, Nakao A. Recent advances in hydrogen research as a therapeutic medical gas. Free Radic Res 2010; 44: 971-982
  • 21 Ishibashi T, Sato B, Rikitake M, Seo T, Kurokawa R, Hara Y, Naritomi Y, Hara H, Nagao T. 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. Med Gas Res 2012; 2: 27
  • 22 Ito M, Ibi T, Sahashi K, Ichihara M, Ito M, Ohno K. Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies. Med Gas Res 2011; 1: 24
  • 23 Itoh T, Fujita Y, Ito M, Masuda A, Ohno K, Ichihara M, Kojima T, Nozawa Y, Ito M. Molecular hydrogen suppresses FcepsilonRI-mediated signal transduction and prevents degranulation of mast cells. Biochem Biophys Res Commun 2009; 389: 651-656
  • 24 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. Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. Nutr Res 2008; 28: 137-143
  • 25 Kamimura N, Nishimaki K, Ohsawa I, Ohta S. Molecular hydrogen improves obesity and diabetes by inducing hepatic FGF21 and stimulating energy metabolism in db/db mice. Obesity 2011; 19: 1396-1403
  • 26 Kang KM, Kang YN, Choi IB, Gu Y, Kawamura T, Toyoda Y, Nakao A. Effects of drinking hydrogen-rich water on the quality of life of patients treated with radiotherapy for liver tumors. Med Gas Res 2011; 1: 11
  • 27 Kawasaki H, Guan J, Tamama K. Hydrogen gas treatment prolongs replicative lifespan of bone marrow multipotential stromal cells in vitro while preserving differentiation and paracrine potentials. Biochem Biophys Res Commun 2010; 397: 608-613
  • 28 Lafay V, Barthelemy P, Comet B, Frances Y, Jammes Y. ECG changes during the experimental human dive HYDRA 10 (71 atm/7,200 kPa). Undersea Hyperb Med 1995; 22: 51-60
  • 29 Levitt MD. Production and excretion of hydrogen gas in man. N Engl J Med 1969; 281: 122-127
  • 30 Liu S, Sun Q, Tao H, Sun X. Oral administration of mannitol may be an effective treatment for ischemia-reperfusion injury. Med Hypotheses 2010; 75: 620-622
  • 31 Liu S, Sun X, Tao X. Hydrogen: form a biologically inert gas to a unique antioxidant. In: Lushchak V. (ed.) Oxidative Stress – Molecular Mechanisms and Biological Effects. Rijeka: InTech; 2012: 135-144
  • 32 Matsumoto S, Ueda T, Kakizaki H. Effect of supplementation with hydrogen-rich water in patients with interstitial cystitis/painful bladder syndrome. Urology 2013; 81: 226-230
  • 33 Miljkovic D. U.S. Patent No. WO2010147751. Washington: U.S. Patent and Trademark Office; 2010
  • 34 Morris DM, Kearney JT, Burke ER. The effects of breathing supplemental oxygen during altitude training on cycling performance. J Sci Med Sport 2000; 3: 165-175
  • 35 Nakao A, Sugimoto R, Billiar TR, McCurry KR. Therapeutic antioxidant medical gas. J Clin Biochem Nutr 2009; 44: 1-13
  • 36 Nakao A, Toyoda Y, Sharma P, Evans M, Guthrie N. Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome – an open label pilot study. J Clin Biochem Nutr 2010; 46: 140-149
  • 37 Nakashima-Kamimura N, Mori T, Ohsawa I, Asoh S, Ohta S. Molecular hydrogen alleviates nephrotoxicity induced by an anti-cancer drug cisplatin without compromising anti-tumor activity in mice. Cancer Chemother Pharmacol 2009; 64: 753-761
  • 38 Nakayama M, Nakano H, Hamada H, Itami N, Nakazawa R, Ito S. A novel bioactive haemodialysis system using dissolved dihydrogen (H2) produced by water electrolysis: a clinical trial. Nephrol Dial Transplant 2010; 25: 3026-3033
  • 39 Oharazawa H, Igarashi T, Yokota T, Fujii H, Suzuki H, Machide M, Takahashi H, Ohta S, Ohsawa I. Protection of the retina by rapid diffusion of hydrogen: administration of hydrogen-loaded eye drops in retinal ischemia-reperfusion injury. Invest Ophthalmol Vis Sci 2010; 51: 487-492
  • 40 Ohno K, Ito M, Ichicara M, Ito M. Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases. Oxid Med Cell Longev 2012; 2012: 353152
  • 41 Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, Katsura K, Katayama Y, Asoh S, Ohta S. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med 2007; 13: 688-694
  • 42 Ohta S. Recent progress toward hydrogen medicine: potential of molecular hydrogen for preventive and therapeutic applications. Curr Pharm Des 2011; 17: 2241-2252
  • 43 Ohta S. Molecular hydrogen is a novel antioxidant to efficiently reduce oxidative stress with potential for the improvement of mitochondrial disease. Biochim Biophys Acta 2012; 1820: 586-594
  • 44 Ohta S, Nakao A, Ohno K. The 2011 Medical Molecular Hydrogen Symposium: An inaugural symposium of the journal Medical Gas Research. Med Gas Res 2011; 1: 10
  • 45 Ono H, Nishijima Y, Adachi N, Tachibana S, Chitoku S, Mukaihara S, Sakamoto M, Kudo Y, Nakazawa J, Kaneko K, Nawashiro H. 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. Med Gas Res 2011; 1: 12
  • 46 Ostojic SM. Serum alkalinization and hydrogen-rich water in healthy men. Mayo Clin Proc 2012; 87: 501-502
  • 47 Ostojic SM, Stojanovic MD, Hoffman JR. Effectiveness of molecular hydrogen in the management of musculotendinous injuries. Med Sci Sport Exerc 2014; 46: S156-S157
  • 48 Ostojic SM, Stojanovic MD. Hydrogen-rich water affected blood alkalinity in physically active men. Res Sports Med 2014; 22: 49-60
  • 49 Ostojic SM, Stojanovic MD, Calleja-Gonzalez J, Obrenovic MD, Veljovic D, Medjedovic B. Drink with alkaline NORP improve exercise performance in physically active men and women. Serb J Sports Sci 2011; 5: 83-89
  • 50 Palange P, Crimi E, Pellegrino R, Brusasco V. Supplemental oxygen and heliox: ‘new’ tools for exercise training in chronic obstructive pulmonary disease. Curr Opin Pulm Med 2005; 11: 145-148
  • 51 Powers SK, Jackson MJ. Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production. Physiol Rev 2008; 88: 1243-1276
  • 52 Pyne DB. Exercise-induced muscle damage and inflammation: a review. Aust J Sci Med Sport 1994; 26: 49-58
  • 53 Robergs RA, Ghiasvand F, Parker D. Biochemistry of exercise-induced metabolic acidosis. Am J Physiol 2004; 287: R502-R516
  • 54 Sato Y, Kajiyama S, Amano A, Kondo Y, Sasaki T, Handa S, Takahashi R, Fukui M, Hasegawa G, Nakamura N, Fujinawa H, Mori T, Ohta M, Obayashi H, Maruyama N, Ishigami A. Hydrogen-rich pure water prevents superoxide formation in brain slices of vitamin C-depleted SMP30/GNL knockout mice. Biochem Biophys Res Commun 2008; 375: 346-350
  • 55 Schlapbach L, Züttel A. Hydrogen-storage materials for mobile applications. Nature 2001; 414: 353-358
  • 56 Shimouchi A, Nose K, Shirai M, Kondo T. Estimation of molecular hydrogen consumption in the human whole body after the ingestion of hydrogen-rich water. Adv Exp Med Biol 2012; 737: 245-250
  • 57 Shimouchi A, Nose K, Takaoka M, Hayashi H, Kondo T. Effect of dietary turmeric on breath hydrogen. Dig Dis Sci 2009; 54: 1725-1729
  • 58 Suzuki Y, Sano M, Hayashida K, Ohsawa I, Ohta S, Fukuda K. Are the effects of alpha-glucosidase inhibitors on cardiovascular events related to elevated levels of hydrogen gas in the gastrointestinal tract?. FEBS Lett 2009; 583: 2157-2159
  • 59 Ueda Y, Nakajima A, Oikawa T. Hydrogen-related enhancement of in vivo antioxidant ability in the brain of rats fed coral calcium hydride. Neurochem Res 2010; 35: 1510-1515
  • 60 Vina J, Borras C, Gomez-Cabrera MC, Orr WC. Part of the series: from dietary antioxidants to regulators in cellular signalling and gene expression. Role of reactive oxygen species and (phyto)oestrogens in the modulation of adaptive response to stress. Free Radic Res 2006; 40: 111-119
  • 61 Yoritaka A, Takanashi M, Hirayama M, Nakahara T, Ohta S, Hattori N. Pilot study of H2 therapy in Parkinson’s disease: A randomized double-blind placebo-controlled trial. Mov Disord 2013; 28: 836-839
  • 62 Zheng XF, Sun XJ, Xia ZF. Hydrogen resuscitation, a new cytoprotective approach. Clin Exp Pharmacol Physiol 2011; 38: 155-163