Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Hydrogen Gas as an Exotic Performance-Enhancing Agent: Challenges and Opportunities

Author(s): Sergej M. Ostojic*

Volume 27, Issue 5, 2021

Published on: 22 September, 2020

Page: [723 - 730] Pages: 8

DOI: 10.2174/1381612826666200922155242

Price: $65

Abstract

Background: Hydrogen gas (H2) has entered the world of experimental therapeutics approximately four and a half decades ago. Over the years, this simple molecule appears to drive more scientific attention, perhaps due to a dualism of H2 affirmative features demonstrated in numerous in vitro, animal and human studies on one side, and still puzzling mechanism(s) of its biological activity on the other. Up to this point, H2 was scrutinized for more than 170 different disease models and pathologies, and many research groups across the world have lately started to dynamically investigate its conceivable performance-enhancing potential.

Methods: We outlined here the studies indexed in leading research databases (PubMed, Web of Science, SCOPUS, JSTORE) that explored the effects of hydrogen on exercise performance, and also addressed important restraints, open questions, and windows of opportunities for forthcoming research and possible H2 enactment in exercise physiology. About two dozen trials have been identified in this domain, with most of the trials published during the past 5 years, while drinking hydrogen-rich water recognized as the most convenient method to deliver H2 in both animal and human studies.

Results: Either administered as an inhalational gas, enteral hydrogen-rich water, or intravenous hydrogen-rich saline, H2 seems to favorably affect various exercise performance outcomes and biomarkers of exercise-associated fatigue, inflammation, and oxidative stress. Not all studies have shown corroborative effects, and it appears that the gold-standard protocol for applying H2 in the field of exercise science does not exist at the moment, with studies markedly differ in the dose of H2 administered, the duration of treatment, and the source of hydrogen.

Conclusion: H2 is a newfangled and rather effective performance-enhancing agent, yet its promising ergogenic potency has to be further validated and characterized in more well-controlled, appropriately sampled and longterm mechanistic trials. Also, appropriate regulation of hydrogen utilization in sport as an exotic medical gas may require distinctive legislative actions of relevant regulatory agencies in the future.

Keywords: Hydrogen, exercise, ergogenic, inhalation, hydrogen-rich water, running, hydrogen-rich saline.

[1]
Dole M, Wilson FR, Fife WP. Hyperbaric hydrogen therapy: a possible treatment for cancer. Science 1975; 190(4210): 152-4.
[http://dx.doi.org/10.1126/science.1166304] [PMID: 1166304]
[2]
Ohsawa I, Ishikawa M, Takahashi K, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med 2007; 13(6): 688-94.
[http://dx.doi.org/10.1038/nm1577] [PMID: 17486089]
[3]
Ostojic SM. Hydrogen studies at ClinicalTrials.gov: the dawn of a new era? Am J Med Sci 2020; 359(1): 51-3.
[http://dx.doi.org/10.1016/j.amjms.2019.10.011] [PMID: 31902441]
[4]
Ohta S. Molecular hydrogen as a preventive and therapeutic medical gas: initiation, development and potential of hydrogen medicine. Pharmacol Ther 2014; 144(1): 1-11.
[http://dx.doi.org/10.1016/j.pharmthera.2014.04.006] [PMID: 24769081]
[5]
Ostojic SM. Molecular hydrogen in sports medicine: new therapeutic perspectives. Int J Sports Med 2015; 36(4): 273-9.
[PMID: 25525953]
[6]
Rostain JC, Gardette-Chauffour MC, Lemaire C, Naquet R. Effects of a H2-He-O2 mixture on the HPNS up to 450 msw. Undersea Biomed Res 1988; 15(4): 257-70.
[PMID: 3212843]
[7]
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(3): 1113-8.
[http://dx.doi.org/10.1152/jappl.1994.76.3.1113] [PMID: 8005852]
[8]
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(1): 51-60.
[PMID: 7742710]
[9]
Fontanari P, Badier M, Guillot C, et al. Changes in maximal performance of inspiratory and skeletal muscles during and after the 7.1-MPa Hydra 10 record human dive. Eur J Appl Physiol 2000; 81(4): 325-8.
[http://dx.doi.org/10.1007/s004210050050] [PMID: 10664092]
[10]
Nogueira JE, Passaglia P, Mota CMD, et al. Molecular hydrogen reduces acute exercise-induced inflammatory and oxidative stress status. Free Radic Biol Med 2018; 129: 186-93.
[http://dx.doi.org/10.1016/j.freeradbiomed.2018.09.028] [PMID: 30243702]
[11]
Nogueira JE, de Deus JL, Amorim MR, et al. Inhaled molecular hydrogen attenuates intense acute exercise-induced hippocampal inflammation in sedentary rats. Neurosci Lett 2020; 715: 134577.
[http://dx.doi.org/10.1016/j.neulet.2019.134577] [PMID: 31715290]
[12]
Korovljev D, Stajer V, Javorac D, Ostojic SM. Hydrogen inhalation positively affects cardiometabolic risk factors in men and women aged 65 years or older: a preliminary report. Eur Geriatr Med 2018; 9: 729.
[http://dx.doi.org/10.1007/s41999-018-0087-6]
[13]
Javorac D, Stajer V, Ratgeber L, Betlehem J, Ostojic SM. Short-term H2 inhalation improves exercise performance in healthy adults. Biol Sport 2019; 36(4): 333-9.
[http://dx.doi.org/10.5114/biolsport.2019.88756] [PMID: 31938004]
[14]
Koyama K, Tanaka Y, Saihara Y, Ando D, Goto Y, Katayama A. Effect of hydrogen saturated alkaline electrolyzed water on urinary oxidative stress markers after an acute exercise: A randomized controlled trial. Anti-aging Med 2008; 4: 117-22.
[15]
Fujita R, Tanaka Y, Saihara Y, Yamakita M, Ando D, Koyama K. Effect of molecular hydrogen saturated alkaline electrolyzed water on disuse muscle atrophy in gastrocnemius muscle. J Physiol Anthropol 2011; 30(5): 195-201.
[http://dx.doi.org/10.2114/jpa2.30.195] [PMID: 21963827]
[16]
Ostojic SM. Serum alkalinization and hydrogen-rich water in healthy men. Mayo Clin Proc 2012; 87(5): 501-2.
[http://dx.doi.org/10.1016/j.mayocp.2012.02.008] [PMID: 22560529]
[17]
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.
[http://dx.doi.org/10.1186/2045-9912-2-12] [PMID: 22520831]
[18]
Tsubone H, Hanafusa M, Endo M, et al. Effect of treadmill exercise and hydrogen-rich water intake on serum oxidative and anti-oxidative metabolites in serum of thoroughbred horses. J Equine Sci 2013; 24(1): 1-8.
[http://dx.doi.org/10.1294/jes.24.1] [PMID: 24833996]
[19]
Ostojic SM, Stojanovic MD. Hydrogen-rich water affected blood alkalinity in physically active men. Res Sports Med 2014; 22(1): 49-60.
[http://dx.doi.org/10.1080/15438627.2013.852092] [PMID: 24392771]
[20]
Drid P, Trivic T, Casals C, Trivic S, Stojanovic M, Ostojic SM. Is molecular hydrogen beneficial to enhance post-exercise recovery in female athletes? Sci Sports 2016; 31(4): 207-13.
[http://dx.doi.org/10.1016/j.scispo.2016.04.010]
[21]
Sun YP, Sun L. Selective protective effect of hydrogen water on free radical injury of athletes after high-intensity exercise. Biomed Res (Aligarh) 2017; 28(10): 4558-61.
[22]
Hasegawa S, Ito M, Fukami M, Hashimoto M, Hirayama M, Ohno K. Molecular hydrogen alleviates motor deficits and muscle degeneration in mdx mice. Redox Rep 2017; 22(1): 26-34.
[http://dx.doi.org/10.1080/13510002.2015.1135580] [PMID: 26866650]
[23]
Shibayama Y, Takeuchi K, Dobashi S, Koyama K. Hydrogen-rich water modulates redox status repeated three consecutive days of strenuous exercise. Med Sci Sports Exerc 2017; 49: 941.
[http://dx.doi.org/10.1249/01.mss.0000519562.97355.a8]
[24]
Trivic T, Vojnovic M, Drid P, Ostojic SM. Drinking hydrogen-rich water for 4 weeks positively affects serum antioxidant enzymes in healthy men. Curr Top Nutraceutical Res 2017; 15(1): 45-8.
[25]
Ostojic SM, Korovljev D, Stajer V, et al. 28-day hydrogen-rich water supplementation affects exercise capacity in mid-age overweight women. Med Sci Sports Exerc 2018; 49(5): S606.
[http://dx.doi.org/10.1249/01.mss.0000538402.25953.d2]
[26]
Da Ponte A, Giovanelli N, Nigris D, Lazzer S. Effects of hydrogen rich water on prolonged intermittent exercise. J Sports Med Phys Fitness 2018; 58(5): 612-21.
[PMID: 28474871]
[27]
Ara J, Fadriquela A, Ahmed MF, et al. Hydrogen water drinking exerts antifatigue effects in chronic forced swimming mice via antioxidative and anti-inflammatory activities. BioMed Res Int 2018; 2018: 2571269.
[http://dx.doi.org/10.1155/2018/2571269] [PMID: 29850492]
[28]
Botek M, Krejčí J, McKune AJ, Sládečková B, Naumovski N. Hydrogen rich water improved ventilatory, perceptual and lactate responses to exercise. Int J Sports Med 2019; 40(14): 879-85.
[http://dx.doi.org/10.1055/a-0991-0268] [PMID: 31574544]
[29]
LeBaron TW, Larson AJ, Ohta S, et al. Acute supplementation with molecular hydrogen benefits submaximal exercise indices. randomized, double-blinded, placebo-controlled crossover pilot study. J Lifestyle Med 2019; 9(1): 36-43.
[http://dx.doi.org/10.15280/jlm.2019.9.1.36] [PMID: 30918832]
[30]
Sha JB, Zhang SS, Lu YM, et al. 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. Med Gas Res 2019; 8(4): 135-43.
[PMID: 30713665]
[31]
Zhang S, Zhang L, Sha J. Effects of long-time drinking hydrogen-rich water on oxidative/antioxidative capacity in endurance training rats. Chin J Rehabil Med 2019; 34(10): 1150-6.
[32]
Mikami T, Tano K, Lee H, et al. Drinking hydrogen water enhances endurance and relieves psychometric fatigue: a randomized, double-blind, placebo-controlled study. Can J Physiol Pharmacol 2019; 97(9): 857-62.
[http://dx.doi.org/10.1139/cjpp-2019-0059] [PMID: 31251888]
[33]
Ooi CH, Ng SK, Omar EA. Acute ingestion of hydrogen-rich water does not improve incremental treadmill running performance in endurance-trained athletes. Appl Physiol Nutr Metab 2020; 45(5): 513-9.
[http://dx.doi.org/10.1139/apnm-2019-0553] [PMID: 31675478]
[34]
Yamazaki M, Kusano K, Ishibashi T, Kiuchi M, Koyama K. Intravenous infusion of H2-saline suppresses oxidative stress and elevates antioxidant potential in Thoroughbred horses after racing exercise. Sci Rep 2015; 5: 15514.
[http://dx.doi.org/10.1038/srep15514] [PMID: 26493164]
[35]
Feng R, Cai M, Wang X, Zhang J, Tian Z. Early aerobic exercise combined with hydrogen-rich saline as preconditioning protects myocardial injury induced by acute myocardial infarction in rats. Appl Biochem Biotechnol 2019; 187(3): 663-76.
[http://dx.doi.org/10.1007/s12010-018-2841-0] [PMID: 30033489]
[36]
Kawamura T, Gando Y, Takahashi M, Hara R, Suzuki K, Muraoka I. Effects of hydrogen bathing on exercise-induced oxidative stress and delayed-onset muscle soreness. Jap J Phys Fitness Sports Med 2016; 65(3): 297-305.
[http://dx.doi.org/10.7600/jspfsm.65.297]
[37]
Powers SK, Radak Z, Ji LL. Exercise-induced oxidative stress: past, present and future. J Physiol 2016; 594(18): 5081-92.
[http://dx.doi.org/10.1113/JP270646] [PMID: 26893258]
[38]
LeBaron TW, Laher I, Kura B, Slezak J. Hydrogen gas: from clinical medicine to an emerging ergogenic molecule for sports athletes. Can J Physiol Pharmacol 2019; 97(9): 797-807.
[http://dx.doi.org/10.1139/cjpp-2019-0067] [PMID: 30970215]
[39]
Ichihara M, Sobue S, Ito M, Ito M, Hirayama M, Ohno K. Beneficial biological effects and the underlying mechanisms of molecular hydrogen - comprehensive review of 321 original articles. Med Gas Res 2015; 5: 12.
[http://dx.doi.org/10.1186/s13618-015-0035-1] [PMID: 26483953]
[40]
Itoh T, Hamada N, Terazawa R, et al. Molecular hydrogen inhibits lipopolysaccharide/interferon γ-induced nitric oxide production through modulation of signal transduction in macrophages. Biochem Biophys Res Commun 2011; 411(1): 143-9.
[http://dx.doi.org/10.1016/j.bbrc.2011.06.116] [PMID: 21723254]
[41]
Hong YH, Betik AC, McConell GK. Role of nitric oxide in skeletal muscle glucose uptake during exercise. Exp Physiol 2014; 99(12): 1569-73.
[http://dx.doi.org/10.1113/expphysiol.2014.079202] [PMID: 25192731]
[42]
Hong Y, Shao A, Wang J, et al. Neuroprotective effect of hydrogen-rich saline against neurologic damage and apoptosis in early brain injury following subarachnoid hemorrhage: possible role of the Akt/GSK3β signaling pathway. PLoS One 2014; 9(4): e96212.
[http://dx.doi.org/10.1371/journal.pone.0096212] [PMID: 24763696]
[43]
Weeks KL, Bernardo BC, Ooi JYY, Patterson NL, McMullen JR. The IGF1-PI3K-Akt signaling pathway in mediating exercise-induced cardiac hypertrophy and protection. Adv Exp Med Biol 2017; 1000: 187-210.
[http://dx.doi.org/10.1007/978-981-10-4304-8_12] [PMID: 29098623]
[44]
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 (Silver Spring) 2011; 19(7): 1396-403.
[http://dx.doi.org/10.1038/oby.2011.6] [PMID: 21293445]
[45]
Matsumoto A, Yamafuji M, Tachibana T, Nakabeppu Y, Noda M, Nakaya H. Oral ‘hydrogen water’ induces neuroprotective ghrelin secretion in mice. Sci Rep 2013; 3: 3273.
[http://dx.doi.org/10.1038/srep03273] [PMID: 24253616]
[46]
Mifune H, Tajiri Y, Sakai Y, et al. Voluntary exercise is motivated by ghrelin, possibly related to the central reward circuit. J Endocrinol 2020; 244(1): 123-32.
[http://dx.doi.org/10.1530/JOE-19-0213] [PMID: 31629323]
[47]
Ostojic SM. Targeting molecular hydrogen to mitochondria: barriers and gateways. Pharmacol Res 2015; 94: 51-3.
[http://dx.doi.org/10.1016/j.phrs.2015.02.004] [PMID: 25720951]
[48]
Ishibashi T. Therapeutic efficacy of molecular hydrogen: a new mechanistic insight. Curr Pharm Des 2019; 25(9): 946-55.
[http://dx.doi.org/10.2174/1381612825666190506123038] [PMID: 31057105]
[49]
Ostojic SM. Does H2 alter mitochondrial bioenergetics via GHS-R1α activation? Theranostics 2017; 7(5): 1330-2.
[http://dx.doi.org/10.7150/thno.18745] [PMID: 28435468]
[50]
Qiu P, Liu Y, Zhang J. Recent advances in studies of molecular hydrogen against sepsis. Int J Biol Sci 2019; 15(6): 1261-75.
[http://dx.doi.org/10.7150/ijbs.30741] [PMID: 31223285]
[51]
Yu P, Wang Z, Sun X, et al. Hydrogen-rich medium protects human skin fibroblasts from high glucose or mannitol induced oxidative damage. Biochem Biophys Res Commun 2011; 409(2): 350-5.
[http://dx.doi.org/10.1016/j.bbrc.2011.05.024] [PMID: 21596020]
[52]
Zheng H, Yu YS. Chronic hydrogen-rich saline treatment attenuates vascular dysfunction in spontaneous hypertensive rats. Biochem Pharmacol 2012; 83(9): 1269-77.
[http://dx.doi.org/10.1016/j.bcp.2012.01.031] [PMID: 22342731]
[53]
Ren JD, Wu XB, Jiang R, Hao DP, Liu Y. Molecular hydrogen inhibits lipopolysaccharide-triggered NLRP3 inflammasome activation in macrophages by targeting the mitochondrial reactive oxygen species. Biochim Biophys Acta 2016; 1863(1): 50-5.
[http://dx.doi.org/10.1016/j.bbamcr.2015.10.012] [PMID: 26488087]
[54]
Lancha AH Junior, Painelli Vde S, Saunders B, Artioli GG. Nutritional strategies to modulate intracellular and extracellular buffering capacity during high-intensity exercise Sports Med 2015; 715: 134577.
[55]
Ostojic SM. Are there natural spring waters rich in molecular hydrogen? Trends Food Sci Technol 2019; 90: 157.
[http://dx.doi.org/10.1016/j.tifs.2019.06.008]
[56]
Smith NW, Shorten PR, Altermann EH, Roy NC, McNabb WC. Hydrogen cross-feeders of the human gastrointestinal tract. Gut Microbes 2019; 10(3): 270-88.
[http://dx.doi.org/10.1080/19490976.2018.1546522] [PMID: 30563420]
[57]
Ostojic SM. Molecular hydrogen: An inert gas turns clinically effective. Ann Med 2015; 47(4): 301-4.
[http://dx.doi.org/10.3109/07853890.2015.1034765] [PMID: 25936365]
[58]
Coleman N. Gastrointestinal issues in athletes. Curr Sports Med Rep 2019; 18(6): 185-7.
[http://dx.doi.org/10.1249/JSR.0000000000000599] [PMID: 31385832]
[59]
The World Anti-Doping Agency. Prohibited List 2019. Available from: https://www.wada-ama.org/en/resources/science-medicine/prohibited-list-documents
[60]
Ostojic SM. Medical gases as an emerging topic in sports medicine. Sports Med 2018; 48(11): 2677-8.
[http://dx.doi.org/10.1007/s40279-018-0948-7] [PMID: 29916152]
[61]
HTWO Hydrogen water success stories 2019. Available from: https://htwo.com
[62]
Good news matters: hydrogen water produces several health benefits. 2019. Available from: http://www.arkansasmatters.com/news/local-news/good-news-matters-hydrogen-water-produces-several-health-benefits/443773504
[63]
Byrne CS, Preston T, Brignardello J, et al. The effect of L-rhamnose on intestinal transit time, short chain fatty acids and appetite regulation: a pilot human study using combined 13CO2/H2 breath tests. J Breath Res 2018; 12(4): 046006.
[http://dx.doi.org/10.1088/1752-7163/aad3f1] [PMID: 30015629]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy