pulmoПульмонологияPULMONOLOGIYA0869-01892541-9617Scientific and Practical Journal “PULMONOLOGIYA” LLC10.18093/0869-0189-2024-34-5-615-623pulmo-4512Research ArticleПЕРЕДОВАЯ СТАТЬЯEDITORIALТерапия водородом: от идеи до практического примененияHydrogen therapy from the initiation to its practical applicationshttps://orcid.org/0000-0002-2539-470XОтаШ.OhtaSh.

Шигео Ота – профессор кафедры неврологии Медицинского факультета Высшей медицинской школы Университета Дзюнтендо и Института передовых медицинских наук МУ Ниппон.

2-1-1, Хонго, Бункё-ку, Токио, 113-8421; 1-25-16, Нэдзу, Бункё-ку, Токио, 113-8602

Shigeo Ohta - Professor, Department of Neurology Medicine, Department of Neurology Medicine, Juntendo University Graduate School of Medicine.

2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421; 1-25-16, Nezu, Bunkyo-ku, Tokyo, 113-8602

ohta@nms.ac.jpВысшая медицинская школа Университет Дзюнтендо; Институт передовых медицинских наук Медицинского университета НиппонЯпонияJuntendo University Graduate School of Medicine; Institure for Advanced Medical Sciences, Nippon Medical UniversityJapan202410102024345624633Copyright © Ота Ш., 20242024Ота Ш.Ohta S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.pulmonology.ru/pulm/article/view/4512

Молекулярный водород (H2) представляется лечебно-профилактическим средством без побочных эффектов. H2 оказывает многогранное действие на различные типы клеток и органов благодаря взаимодействию с окисленными гемами по фундаментальному молекулярному механизму. Широкое действие H2 объясняется обилием различных типов гемов как внутри, так и вне клеток. Запускаемые им пути опосредованы конечными или модифицированными продуктами перекисного окисления липидов и последующими свободнорадикальными цепными реакциями. Примечательно, что H2 приносит пользу не только больным, но и здоровым людям, стремящимся улучшить свое здоровье и общее самочувствие. Миссия водородной медицины состоит в решении актуальных медицинских проблем, включая терапию при инфаркте мозга, постасистолическом синдроме, распространенных раковых заболеваниях, метаболическом синдроме и деменции. Для эффективной борьбы с этими грозными заболеваниями необходимо перейти от экспериментов на животных к клиническим исследованиям.

Molecular hydrogen (H2) has emerged as a therapeutic and prophylactic agent devoid of adverse effects. H2 demonstrates multifaceted functionality across diverse cell types and organs, attributable to its interaction with oxidized hemes as a fundamental molecular mechanism. Given the abundance of various heme types both intracellularly and extracellularly, the broad-ranging effects of H2 are comprehensible. Subsequent Pathways are mediated by end-or modified- products of lipid peroxide followed by free radical chain reactions. Notably, H2 confers benefits not only to patients afflicted with diseases but also to individuals seeking to enhance health and wellness. The mission of hydrogen medicine encompasses addressing unresolved medical challenges, including cerebral infarction, post-cardiac arrest syndrome, advanced cancer, metabolic syndrome, and dementia. Transitioning from animal experiments to clinical studies is imperative to confront these formidable diseases effectively.

побочный эффектболезнь Альцгеймераракостановка сердцаклиническое исследованиегемводородная медицинаперекисное окисление липидовметаболический синдроммножественные функцииокислениепорфиринпередача сигналаadverse effectAlzheimer’s diseasecancercardiac arrestclinical trialhemehydrogen medicinelipid peroxidemetabolic syndromemultiple functionsoxidationporphyrinsignal transductionquarity-of-lifeСпонсорская поддержка отсутствовалаThis study was not sponsoredReferencesYagi T., Higuchi Y. Studies on hydrogenase. Proc. Jpn. Acad. Ser. B Phys. Biol. Sci. 2013; 89 (1): 16–33. DOI: 10.2183/pjab.89.16.Yagi T., Higuchi Y. Studies on hydrogenase. Proc. Jpn. Acad. Ser. B Phys. Biol. Sci. 2013; 89 (1): 16–33. DOI: 10.2183/pjab.89.16.Hansen M., Perner M. Hydrogenase gene distribution and H2 consumption ability within the Thiomicrospira lineage. Front. Microbiol. 2016; 7; 99. DOI: 10.3389/fmicb.2016.00099.Hansen M., Perner M. Hydrogenase gene distribution and H2 consumption ability within the Thiomicrospira lineage. Front. Microbiol. 2016; 7; 99. DOI: 10.3389/fmicb.2016.00099.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): 688–694. DOI: 10.1038/nm1577.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): 688–694. DOI: 10.1038/nm1577.Ohta S. Development of hydrogen medicine and biology: potential for various applications in diverse fields. Curr. Pharm. Des. 2021; 27 (5): 583–584. DOI: 10.2174/138161282705210211144515.Ohta S. Development of hydrogen medicine and biology: potential for various applications in diverse fields. Curr. Pharm. Des. 2021; 27 (5): 583–584. DOI: 10.2174/138161282705210211144515.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. DOI: 10.1016/j.pharmthera.2014.04.006.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. DOI: 10.1016/j.pharmthera.2014.04.006.Li L., Lou W., Kong L., Shen W. Hydrogen commonly applicable from medicine to agriculture: from molecular mechanisms to the field. Curr. Pharm. Des. 2021; 27 (5): 747–759. DOI: 10.2174/1381612826666201207220051.Li L., Lou W., Kong L., Shen W. Hydrogen commonly applicable from medicine to agriculture: from molecular mechanisms to the field. Curr. Pharm. Des. 2021; 27 (5): 747–759. DOI: 10.2174/1381612826666201207220051.Sano M., Ichihara G., Katsumata Y. et al. Pharmacokinetics of a single inhalation of hydrogen gas in pigs. PLoS One. 2020; 15 96): e0234626. DOI: 10.1371/journal.pone.0234626.Sano M., Ichihara G., Katsumata Y. et al. Pharmacokinetics of a single inhalation of hydrogen gas in pigs. PLoS One. 2020; 15 96): e0234626. DOI: 10.1371/journal.pone.0234626.Ichihara G., Katsumata Y., Moriyama H. et al. Pharmacokinetics of hydrogen after ingesting a hydrogen-rich solution: a study in pigs. Heliyon. 2021; 7 (11): e08359. DOI: 10.1016/j.heliyon.2021.e08359.Ichihara G., Katsumata Y., Moriyama H. et al. Pharmacokinetics of hydrogen after ingesting a hydrogen-rich solution: a study in pigs. Heliyon. 2021; 7 (11): e08359. DOI: 10.1016/j.heliyon.2021.e08359.Li J., Wang C., Zhang J.H. et al. Hydrogen-rich saline improves memory function in a rat model of amyloid-beta-induced Alzheimer's disease by reduction of oxidative stress. Brain Res. 2010; 1328: 152–161. DOI: 10.1016/j.brainres.2010.02.046.Li J., Wang C., Zhang J.H. et al. Hydrogen-rich saline improves memory function in a rat model of amyloid-beta-induced Alzheimer's disease by reduction of oxidative stress. Brain Res. 2010; 1328: 152–161. DOI: 10.1016/j.brainres.2010.02.046.Takahashi H. Application of hydrogen in ophthalmology. Curr. Pharm. Des. 2021; 27 (5): 592–594. DOI: 10.2174/1381612826666201019103446.Takahashi H. Application of hydrogen in ophthalmology. Curr. Pharm. Des. 2021; 27 (5): 592–594. DOI: 10.2174/1381612826666201019103446.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): 325–328. DOI: 10.1007/s004210050050.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): 325–328. DOI: 10.1007/s004210050050.Cole A.R., Sperotto F., DiNardo J.A. et al. Safety of prolonged inhalation of hydrogen gas in air in healthy adults. Crit. Care Explor. 2021; 3 (10): e543. DOI: 10.1097/cce.0000000000000543.Cole A.R., Sperotto F., DiNardo J.A. et al. Safety of prolonged inhalation of hydrogen gas in air in healthy adults. Crit. Care Explor. 2021; 3 (10): e543. DOI: 10.1097/cce.0000000000000543.Ohta S. Direct targets and subsequent pathways for molecular hydrogen to exert multiple functions: focusing on interventions in radical reactions. Curr. Pharm. Des. 2021; 27 (5): 595–609. DOI: 10.2174/1381612826666200806101137.Ohta S. Direct targets and subsequent pathways for molecular hydrogen to exert multiple functions: focusing on interventions in radical reactions. Curr. Pharm. Des. 2021; 27 (5): 595–609. DOI: 10.2174/1381612826666200806101137.Wood K.C., Gladwin M.T. The hydrogen highway to reperfusion therapy. Nat. Med. 2007; 13 (6): 673–674. DOI: 10.1038/nm0607-673.Wood K.C., Gladwin M.T. The hydrogen highway to reperfusion therapy. Nat. Med. 2007; 13 (6): 673–674. DOI: 10.1038/nm0607-673.Jin Z., Zhao P., Gong W. et al. Fe-porphyrin: a redox-related biosensor of hydrogen molecule. Nano Research. 2023; 16 (2): 2020–2025. DOI: 10.1007/s12274-022-4860-y.Jin Z., Zhao P., Gong W. et al. Fe-porphyrin: a redox-related biosensor of hydrogen molecule. Nano Research. 2023; 16 (2): 2020–2025. DOI: 10.1007/s12274-022-4860-y.Sun X., Ohta S., Zhang J.H. Discovery of a hydrogen molecular target. Med. Gas Res. 2023; 13 (2): 41–42. DOI: 10.4103/2045-9912.356472.Sun X., Ohta S., Zhang J.H. Discovery of a hydrogen molecular target. Med. Gas Res. 2023; 13 (2): 41–42. DOI: 10.4103/2045-9912.356472.Ohta S. Molecular hydrogen may activate the transcription factor Nrf2 to alleviate oxidative stress through the hydrogen-targeted porphyrin. Aging Pathobiol. Ther. 2023; 5 (1): 25–32. DOI: 10.31491/APT.2023.03.104.Ohta S. Molecular hydrogen may activate the transcription factor Nrf2 to alleviate oxidative stress through the hydrogen-targeted porphyrin. Aging Pathobiol. Ther. 2023; 5 (1): 25–32. DOI: 10.31491/APT.2023.03.104.Zhou Y., Wu H., Zhao M. et al. The Bach family of transcription factors: a comprehensive review. Clin. Rev. Allergy Immunol. 2016; 50 (3): 345–356. DOI: 10.1007/s12016-016-8538-7.Zhou Y., Wu H., Zhao M. et al. The Bach family of transcription factors: a comprehensive review. Clin. Rev. Allergy Immunol. 2016; 50 (3): 345–356. DOI: 10.1007/s12016-016-8538-7.Igarashi K., Kurosaki T., Roychoudhuri R. BACH transcription factors in innate and adaptive immunity. Nat. Rev. Immunol. 2017; 17 (7): 437–450. DOI: 10.1038/nri.2017.26.Igarashi K., Kurosaki T., Roychoudhuri R. BACH transcription factors in innate and adaptive immunity. Nat. Rev. Immunol. 2017; 17 (7): 437–450. DOI: 10.1038/nri.2017.26.Song Q., Mao X., Jing M. et al. Pathophysiological role of BACH transcription factors in digestive system diseases. Front. Physiol. 2023; 14: 1121353. DOI: 10.3389/fphys.2023.1121353.Song Q., Mao X., Jing M. et al. Pathophysiological role of BACH transcription factors in digestive system diseases. Front. Physiol. 2023; 14: 1121353. DOI: 10.3389/fphys.2023.1121353.Dixon S.J., Pratt D.A. Ferroptosis: A flexible constellation of related biochemical mechanisms. Mol. Cell. 2023; 83 (7): 1030–1042. DOI: 10.1016/j.molcel.2023.03.005.Dixon S.J., Pratt D.A. Ferroptosis: A flexible constellation of related biochemical mechanisms. Mol. Cell. 2023; 83 (7): 1030–1042. DOI: 10.1016/j.molcel.2023.03.005.Iuchi K., Nishimaki K., Kamimura N., Ohta S. Molecular hydrogen suppresses free-radical-induced cell death by mitigating fatty acid peroxidation and mitochondrial dysfunction. Can. J. Physiol. Pharmacol. 2019; 97 (10): 999–1005. DOI: 10.1139/cjpp-2018-0741.Iuchi K., Nishimaki K., Kamimura N., Ohta S. Molecular hydrogen suppresses free-radical-induced cell death by mitigating fatty acid peroxidation and mitochondrial dysfunction. Can. J. Physiol. Pharmacol. 2019; 97 (10): 999–1005. DOI: 10.1139/cjpp-2018-0741.Kamimura N., Ichimiya H., Iuchi K., Ohta S. Molecular hydrogen stimulates the gene expression of transcriptional coactivator PGC-1α to enhance fatty acid metabolism. NPJ. Aging. Mech. Dis. 2016; 2: 16008. DOI: 10.1038/npjamd.2016.8.Kamimura N., Ichimiya H., Iuchi K., Ohta S. Molecular hydrogen stimulates the gene expression of transcriptional coactivator PGC-1α to enhance fatty acid metabolism. NPJ. Aging. Mech. Dis. 2016; 2: 16008. DOI: 10.1038/npjamd.2016.8.Luchi K., Imoto A., Kamimura N. et al. Molecular hydrogen regulates gene expression by modifying the free radical chain reaction-dependent generation of oxidized phospholipid mediators. Sci. Rep. 2016; 6: 18971. DOI: 10.1038/srep18971.Luchi K., Imoto A., Kamimura N. et al. Molecular hydrogen regulates gene expression by modifying the free radical chain reaction-dependent generation of oxidized phospholipid mediators. Sci. Rep. 2016; 6: 18971. DOI: 10.1038/srep18971.Matsumoto A., Yamafuji M., Tachibana T. et al. Oral 'hydrogen water' induces neuroprotective ghrelin secretion in mice. Sci. Rep. 2013; 3: 3273. DOI: 10.1038/srep03273.Matsumoto A., Yamafuji M., Tachibana T. et al. Oral 'hydrogen water' induces neuroprotective ghrelin secretion in mice. Sci. Rep. 2013; 3: 3273. DOI: 10.1038/srep03273.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): 1396–1403. DOI: 10.1038/oby.2011.6.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): 1396–1403. DOI: 10.1038/oby.2011.6.Nicolson G.L., de Mattos G.F., Settineri R. et al. Clinical effects of hydrogen administration: from animal and human diseases to exercise medicine. Int. J. Clin. Med. 2016; 7 (1): 32–76. DOI: 10.4236/ijcm.2016.71005.Nicolson G.L., de Mattos G.F., Settineri R. et al. Clinical effects of hydrogen administration: from animal and human diseases to exercise medicine. Int. J. Clin. Med. 2016; 7 (1): 32–76. DOI: 10.4236/ijcm.2016.71005.Johnsen H.M., Hiorth M., Klaveness J. Molecular hydrogen therapy-a review on clinical studies and outcomes. Molecules. 2023; 28 (23): 7785. DOI: 10.3390/molecules28237785.Johnsen H.M., Hiorth M., Klaveness J. Molecular hydrogen therapy-a review on clinical studies and outcomes. Molecules. 2023; 28 (23): 7785. DOI: 10.3390/molecules28237785.Mizuno K., Sasaki A.T., Ebisu K. et al. Hydrogen-rich water for improvements of mood, anxiety, and autonomic nerve function in daily life. Med. Gas Res. 2018; 7 (4): 247–255. DOI: 10.4103/2045-9912.222448.Mizuno K., Sasaki A.T., Ebisu K. et al. Hydrogen-rich water for improvements of mood, anxiety, and autonomic nerve function in daily life. Med. Gas Res. 2018; 7 (4): 247–255. DOI: 10.4103/2045-9912.222448.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): 857–862. DOI: 10.1139/cjpp-2019-0059.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): 857–862. DOI: 10.1139/cjpp-2019-0059.Botek M., Krejci J., McKune A.J., Sladeckova B. Hydrogen-rich water supplementation and up-hill running performance: effect of athlete performance level. Int. J. Sports Physiol. Perform. 2020; 15 (8): 1193–1196. DOI: 10.1123/ijspp.2019-0507.Botek M., Krejci J., McKune A.J., Sladeckova B. Hydrogen-rich water supplementation and up-hill running performance: effect of athlete performance level. Int. J. Sports Physiol. Perform. 2020; 15 (8): 1193–1196. DOI: 10.1123/ijspp.2019-0507.Ostojic S.M. Hydrogen gas as an exotic performance-enhancing agent: challenges and opportunities. Curr. Pharm. Des. 2021; 27 (5): 723–730. DOI: 10.2174/1381612826666200922155242.Ostojic S.M. Hydrogen gas as an exotic performance-enhancing agent: challenges and opportunities. Curr. Pharm. Des. 2021; 27 (5): 723–730. DOI: 10.2174/1381612826666200922155242.Botek M., Krejci J., McKune A. et al. Hydrogen rich water consumption positively affects muscle performance, lactate response, and alleviates delayed onset of muscle soreness after resistance training. J. Strength Cond. Res. 2022; 36 (10): 2792–2799. DOI: 10.1519/jsc.0000000000003979.Botek M., Krejci J., McKune A. et al. Hydrogen rich water consumption positively affects muscle performance, lactate response, and alleviates delayed onset of muscle soreness after resistance training. J. Strength Cond. Res. 2022; 36 (10): 2792–2799. DOI: 10.1519/jsc.0000000000003979.Zhou K., Liu M., Wang Y. et al. Effects of molecular hydrogen supplementation on fatigue and aerobic capacity in healthy adults: a systematic review and meta-analysis. Front. Nutr. 2023; 10: 1094767. DOI: 10.3389/fnut.2023.1094767.Zhou K., Liu M., Wang Y. et al. Effects of molecular hydrogen supplementation on fatigue and aerobic capacity in healthy adults: a systematic review and meta-analysis. Front. Nutr. 2023; 10: 1094767. DOI: 10.3389/fnut.2023.1094767.Liu H., Kang X., Ren P. et al. Hydrogen gas ameliorates acute alcoholic liver injury via anti-inflammatory and antioxidant effects and regulation of intestinal microbiota. Int. Immunopharmacol. 2023; 120: 110252. DOI: 10.1016/j.intimp.2023.110252.Liu H., Kang X., Ren P. et al. Hydrogen gas ameliorates acute alcoholic liver injury via anti-inflammatory and antioxidant effects and regulation of intestinal microbiota. Int. Immunopharmacol. 2023; 120: 110252. DOI: 10.1016/j.intimp.2023.110252.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. Am. J. Clin. Nutr. 2022; 116 (5): 1208–1218. DOI: 10.1093/ajcn/nqac261.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. Am. J. Clin. Nutr. 2022; 116 (5): 1208–1218. DOI: 10.1093/ajcn/nqac261.Hu A., Yamaguchi T., Tabuchi M. et al. A pilot study to evaluate the potential therapeutic effect of hydrogen-water bathing on atopic dermatitis in humans. Adv. Integr. Med. 2024; 11 (1): 2–9. DOI: 10.1016/j.aimed.2023.10.003.Hu A., Yamaguchi T., Tabuchi M. et al. A pilot study to evaluate the potential therapeutic effect of hydrogen-water bathing on atopic dermatitis in humans. Adv. Integr. Med. 2024; 11 (1): 2–9. DOI: 10.1016/j.aimed.2023.10.003.Bajgai J., Lee K.J., Rahman M.H. et al. Role of molecular hydrogen in skin diseases and its impact in beauty. Curr. Pharm. Des. 2021; 27 (5): 737–746. DOI: 10.2174/1381612826666200925124235.Bajgai J., Lee K.J., Rahman M.H. et al. Role of molecular hydrogen in skin diseases and its impact in beauty. Curr. Pharm. Des. 2021; 27 (5): 737–746. DOI: 10.2174/1381612826666200925124235.Dhillon G., Buddhavarapu V., Grewal H. et al. Hydrogen water: extra healthy or a hoax? – A systematic review. In. J. Mol. Sci. 2024; 25 (2): 973. DOI: 10.3390/ijms25020973.Dhillon G., Buddhavarapu V., Grewal H. et al. Hydrogen water: extra healthy or a hoax? – A systematic review. In. J. Mol. Sci. 2024; 25 (2): 973. DOI: 10.3390/ijms25020973.Ono H., Nishijima Y., Ohta S. et al. Hydrogen gas inhalation treatment in acute cerebral infarction: a randomized controlled clinical study on safety and neuroprotection. J. Stroke Cerebrovasc. Dis. 2017; 26 (11): 2587–2594. DOI: 10.1016/j.jstrokecerebrovasdis.2017.06.012.Ono H., Nishijima Y., Ohta S. et al. Hydrogen gas inhalation treatment in acute cerebral infarction: a randomized controlled clinical study on safety and neuroprotection. J. Stroke Cerebrovasc. Dis. 2017; 26 (11): 2587–2594. DOI: 10.1016/j.jstrokecerebrovasdis.2017.06.012.Hayashida K., Sano M., Kamimura N. et al. Hydrogen inhalation during normoxic resuscitation improves neurological outcome in a rat model of cardiac arrest independently of targeted temperature management. Circulation. 2014; 130 (24): 2173–2180. DOI: 10.1161/circulationaha.114.011848.Hayashida K., Sano M., Kamimura N. et al. Hydrogen inhalation during normoxic resuscitation improves neurological outcome in a rat model of cardiac arrest independently of targeted temperature management. Circulation. 2014; 130 (24): 2173–2180. DOI: 10.1161/circulationaha.114.011848.Tamura T., Suzuki M., Homma K. et al. Efficacy of inhaled hydrogen on neurological outcome following brain ischaemia during post-cardiac arrest care (HYBRID II): a multi-centre, randomised, double-blind, placebo-controlled trial. EClinicalMedicine. 2023; 58: 101907. DOI: 10.1016/j.eclinm.2023.101907.Tamura T., Suzuki M., Homma K. et al. Efficacy of inhaled hydrogen on neurological outcome following brain ischaemia during post-cardiac arrest care (HYBRID II): a multi-centre, randomised, double-blind, placebo-controlled trial. EClinicalMedicine. 2023; 58: 101907. DOI: 10.1016/j.eclinm.2023.101907.Qin S. Role of Hydrogen in atherosclerotic disease: from bench to Bedside. Curr. Pharm. Des. 2021; 27 (5): 713–722. DOI: 10.2174/1381612826666201124112152.Qin S. Role of Hydrogen in atherosclerotic disease: from bench to Bedside. Curr. Pharm. Des. 2021; 27 (5): 713–722. DOI: 10.2174/1381612826666201124112152.Ohsawa I., Nishimaki K., Yamagata K. et al. Consumption of hydrogen water prevents atherosclerosis in apolipoprotein E knockout mice. Biochem. Biophys. Res. Commun. 2008; 377 (4): 1195–1198. DOI: 10.1016/j.bbrc.2008.10.156.Ohsawa I., Nishimaki K., Yamagata K. et al. Consumption of hydrogen water prevents atherosclerosis in apolipoprotein E knockout mice. Biochem. Biophys. Res. Commun. 2008; 377 (4): 1195–1198. DOI: 10.1016/j.bbrc.2008.10.156.Todorovic N., Fernández-Landa J., Santibañez A. et al. The effects of hydrogen-rich water on blood lipid profiles in clinical populations: a systematic review and meta-analysis. Pharmaceuticals (Basel). 2023; 16 (2): 142. DOI: 10.3390/ph16020142.Todorovic N., Fernández-Landa J., Santibañez A. et al. The effects of hydrogen-rich water on blood lipid profiles in clinical populations: a systematic review and meta-analysis. Pharmaceuticals (Basel). 2023; 16 (2): 142. DOI: 10.3390/ph16020142.Nagata K., Nakashima-Kamimura N., Mikami T. et al. Consumption of molecular hydrogen prevents the stress-induced impairments in hippocampus-dependent learning tasks during chronic physical restraint in mice. Neuropsychopharmacology. 2009; 34 (2): 501–508. DOI: 10.1038/npp.2008.95.Nagata K., Nakashima-Kamimura N., Mikami T. et al. Consumption of molecular hydrogen prevents the stress-induced impairments in hippocampus-dependent learning tasks during chronic physical restraint in mice. Neuropsychopharmacology. 2009; 34 (2): 501–508. DOI: 10.1038/npp.2008.95.Nishimaki K., Asada T., Ohsawa I. et al. Effects of molecular hydrogen assessed by an animal model and a randomized clinical study on mild cognitive impairment. Curr. Alzheimer Res. 2018; 15 (5): 482–492. DOI: 10.2174/1567205014666171106145017.Nishimaki K., Asada T., Ohsawa I. et al. Effects of molecular hydrogen assessed by an animal model and a randomized clinical study on mild cognitive impairment. Curr. Alzheimer Res. 2018; 15 (5): 482–492. DOI: 10.2174/1567205014666171106145017.Kueper J.K., Speechley M., Montero-Odasso M. The Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog): modifications and responsiveness in pre-dementia populations. A narrative review. J. Alzheimers Dis. 2018; 63 (2): 423–444. DOI: 10.3233/jad-170991.Kueper J.K., Speechley M., Montero-Odasso M. The Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog): modifications and responsiveness in pre-dementia populations. A narrative review. J. Alzheimers Dis. 2018; 63 (2): 423–444. DOI: 10.3233/jad-170991.Ayyubova G. APOE4 is a risk factor and potential therapeutic target for Alzheimer's disease. CNS Neurol. Disord. Drug Targets. 2024; 23 (3): 342–352. DOI: 10.2174/1871527322666230303114425.Ayyubova G. APOE4 is a risk factor and potential therapeutic target for Alzheimer's disease. CNS Neurol. Disord. Drug Targets. 2024; 23 (3): 342–352. DOI: 10.2174/1871527322666230303114425.Alm K.H., Bakker A. Relationships between diffusion tensor imaging and cerebrospinal fluid metrics in early stages of the Alzheimer's disease continuum. J. Alzheimers Dis. 2019; 70 (4): 965–981. DOI: 10.3233/jad-181210.Alm K.H., Bakker A. Relationships between diffusion tensor imaging and cerebrospinal fluid metrics in early stages of the Alzheimer's disease continuum. J. Alzheimers Dis. 2019; 70 (4): 965–981. DOI: 10.3233/jad-181210.Ono H., Nishijima Y., Ohta S. Therapeutic inhalation of hydrogen gas for Alzheimer's disease patients and subsequent long-term follow-up as a disease-modifying treatment: An open label pilot study. Pharmaceuticals (Basel). 2023; 16 (3): 434. DOI: 10.3390/ph16030434.Ono H., Nishijima Y., Ohta S. Therapeutic inhalation of hydrogen gas for Alzheimer's disease patients and subsequent long-term follow-up as a disease-modifying treatment: An open label pilot study. Pharmaceuticals (Basel). 2023; 16 (3): 434. DOI: 10.3390/ph16030434.Ono H., Nishijima Y., Sakamoto M. et al. Long-term inhalation of hydrogen gas for patients with advanced Alzheimer's disease: a case report showing improvement in fecal Incontinence. Med. Res. Arch. 2022; 10 (7). DOI: 10.18103/mra.v10i7.2951.Ono H., Nishijima Y., Sakamoto M. et al. Long-term inhalation of hydrogen gas for patients with advanced Alzheimer's disease: a case report showing improvement in fecal Incontinence. Med. Res. Arch. 2022; 10 (7). DOI: 10.18103/mra.v10i7.2951.Rahman M.H., Bajgai J., Sharma S. et al. Effects of hydrogen gas inhalation on community-dwelling adults of various ages: a single-arm, open-label, prospective clinical trial. Antioxidants (Basel). 2023; 12 (6): 1241. DOI: 10.3390/antiox12061241.Rahman M.H., Bajgai J., Sharma S. et al. Effects of hydrogen gas inhalation on community-dwelling adults of various ages: a single-arm, open-label, prospective clinical trial. Antioxidants (Basel). 2023; 12 (6): 1241. DOI: 10.3390/antiox12061241.Dan Z., Li H., Xie J. Efficacy of donepezil plus hydrogen-oxygen mixture inhalation for treatment of patients with Alzheimer disease: a retrospective study. Medicine (Baltimore). 2023; 102 (30): e34382. DOI: 10.1097/md.0000000000034382.Dan Z., Li H., Xie J. Efficacy of donepezil plus hydrogen-oxygen mixture inhalation for treatment of patients with Alzheimer disease: a retrospective study. Medicine (Baltimore). 2023; 102 (30): e34382. DOI: 10.1097/md.0000000000034382.He J., Liu F., Xu T. et al. The role of hydrogen therapy in Alzheimer's disease management: Insights into mechanisms, administration routes, and future challenges. Biomed. Pharmacother. 2023; 168: 115807. DOI: 10.1016/j.biopha.2023.115807.He J., Liu F., Xu T. et al. The role of hydrogen therapy in Alzheimer's disease management: Insights into mechanisms, administration routes, and future challenges. Biomed. Pharmacother. 2023; 168: 115807. DOI: 10.1016/j.biopha.2023.115807.Nakashima-Kamimura N., Mori T., Ohsawa I. et al. Molecular hydrogen alleviates nephrotoxicity induced by an anti-cancer drug cisplatin without compromising anti-tumor activity in mice. Cancer Chemother. Pharmacol. 2009; 64 (4): 753–761. DOI: 10.1007/s00280-008-0924-2.Nakashima-Kamimura N., Mori T., Ohsawa I. et al. Molecular hydrogen alleviates nephrotoxicity induced by an anti-cancer drug cisplatin without compromising anti-tumor activity in mice. Cancer Chemother. Pharmacol. 2009; 64 (4): 753–761. DOI: 10.1007/s00280-008-0924-2.Kang K.M., Kang Y.N., Choi I.B. et al. Effects of drinking hydrogen-rich water on the quality of life of patients treated with radiotherapy for liver tumors. Med. Gas Res. 2011; 1 (1): 11. DOI: 10.1186/2045-9912-1-11.Kang K.M., Kang Y.N., Choi I.B. et al. Effects of drinking hydrogen-rich water on the quality of life of patients treated with radiotherapy for liver tumors. Med. Gas Res. 2011; 1 (1): 11. DOI: 10.1186/2045-9912-1-11.Akagi J., Baba H. Hydrogen gas restores exhausted CD8+ T cells in patients with advanced colorectal cancer to improve prognosis. Oncol. Rep. 2019; 41 (1): 301–311. DOI: 10.3892/or.2018.6841.Akagi J., Baba H. Hydrogen gas restores exhausted CD8+ T cells in patients with advanced colorectal cancer to improve prognosis. Oncol. Rep. 2019; 41 (1): 301–311. DOI: 10.3892/or.2018.6841.Akagi J., Baba H. 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. Oncol. Lett. 2020; 20 (5): 258. DOI: 10.3892/ol.2020.12121.Akagi J., Baba H. 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. Oncol. Lett. 2020; 20 (5): 258. DOI: 10.3892/ol.2020.12121.Mohd Noor M.N.Z., Alauddin A.S., Wong Y.H. et al. A systematic review of molecular hydrogen therapy in cancer management. Asian Pac. J. Cancer Prev. 2023; 24 (1): 37–47. DOI: 10.31557/apjcp.2023.24.1.37.Mohd Noor M.N.Z., Alauddin A.S., Wong Y.H. et al. A systematic review of molecular hydrogen therapy in cancer management. Asian Pac. J. Cancer Prev. 2023; 24 (1): 37–47. DOI: 10.31557/apjcp.2023.24.1.37.

The authors declare that there are no conflicts of interest present.