Hydrogen enriched water for mitochondrial and inflammatory myopathiesScientific Research
Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies
https://medicalgasresearch.biomedcentral.com/articles/10.1186/2045-9912-1-24
Abstract
Background
Molecular hydrogen is important in more than 30 animal models, especially in oxidative stress-mediated diseases and inflammatory diseases. Furthermore, hydrogen effects have been reported in human type 2 diabetes, hemodialysis, metabolic syndrome, radiotherapy for liver cancer, and brainstem infarction. The hydrogen effect has been attributed to specific radical scavenging activities to eliminate hydroxyl radicals and peroxynitrite, as well as signal-modulating activities, but the detailed molecular mechanisms remain elusive. Hydrogen is a safe molecule, mainly produced by gut bacteria in rodents and humans, and no adverse effects have been recorded.
Methods
We conducted an open-label study in 5 patients with progressive muscular dystrophy (PMD), 4 patients with polymyositis/dermatomyositis (PM/DM) and 5 patients with mitochondrial myopathy drinking 1.0 liters of rich daily Hydrogen water for 12 weeks (MM). Serum parameters and 8-isoprostaglandin were measured 18 times in urine every 4 weeks. Next, we conducted a randomized, double-blind, placebo-controlled, crossover study of 0.5 liters of hydrogen-rich water per day or placebo water in 10 patients with DM and 12 patients with MM for 8 weeks with 18 measurements each Serum parameters. 4 weeks.
Results
No objective improvement or worsening of clinical symptoms was observed in the open-label study. However, we observed significant effects on lactate to pyruvate ratios in PMD and MM, fasting blood glucose in PMD, serum matrix metalloproteinase-3 (MMP3) in PM/DM, and serum triglycerides in PM/DM. influences. No objective clinical effect was observed in the double-blind study, but a significant improvement in lactate in MM was noted. The lactate to pyruvate ratio in MM and MMP3 in DM also showed good responses, but not statistically significant. No adverse effects were observed in all studies, except for a hypoglycemic event in one MELAS patient receiving insulin, which was resolved by reducing the insulin dose.
Conclusion
Hydrogen-rich water improves mitochondrial dysfunction in MM and inflammatory processes in PM/DM. The less pronounced effect in the double-blind study may be due to the lower amount of hydrogen administered and the shorter observation period compared to the open-label study, suggesting a threshold or dose-response effect of hydrogen.
References
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. 10.1038/nm1577.
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: 10-10.1186/2045-9912-1-10.
Nakao A, Sugimoto R, Billiar TR, McCurry KR: Therapeutic Antioxidant Medical Gas. J Clin Biochem Nutr. 2009, 44: 1-13. 10.3164/jcbn.08-193R.
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.
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. 10.1016/j.bbrc.2009.09.047.
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. 10.1016/j.nutres.2008.01.008.
Nakayama M, Kabayama S, Nakano H, Zhu WJ, Terawaki H, Nakayama K, Katoh K, Satoh T, Ito S: Biological Effects of Electrolyzed Water in Hemodialysis. Nephron Clin Pract. 2009, 112: C9-C15. 10.1159/000210569.
Nakayama M, Nakano H, Hamada H, Itami N, Nakazawa R, Ito S: A novel bioactive haemodialysis system using dissolved dihydrogen (H-2) produced by water electrolysis: a clinical trial. Nephrol Dial Transplant. 2010, 25: 3026-3033. 10.1093/ndt/gfq196.
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. 10.3164/jcbn.09-100.
Kang K-M, Kang Y-N, Choi I-B, 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: 11-10.1186/2045-9912-1-11.
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: 12-10.1186/2045-9912-1-12.
DiMauro S: Pathogenesis and treatment of mitochondrial myopathies: recent advances. Acta Myologica. 2010, 29: 333-338.
Wei YH, Lu CY, Wei CY, Ma YS, Lee HC: Oxidative stress in human aging and mitochondrial disease-consequences of defective mitochondrial respiration and impaired antioxidant enzyme system. Chin J Physiol. 2001, 44: 1-11.
McKenzie M, Liolitsa D, Hanna MG: Mitochondrial disease: mutations and mechanisms. Neurochem Res. 2004, 29: 589-600.
Sternlicht MD, Werb Z: How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol. 2001, 17: 463-516. 10.1146/annurev.cellbio.17.1.463.
Nishijima C, Hayakawa I, Matsushita T, Komura K, Hasegawa M, Takehara K, Sato S: Autoantibody against matrix metalloproteinase-3 in patients with systemic sclerosis. Clin Exp Immunol. 2004, 138: 357-363. 10.1111/j.1365-2249.2004.02615.x.
Fujita K, Seike T, Yutsudo N, Ohno M, Yamada H, Yamaguchi H, Sakumi K, Yamakawa Y, Kido MA, Takaki A, Katafuchi T, Nakabeppu Y, Noda M: Hydrogen in drinking water reduces dopaminergic neuronal loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. PLoS One. 2009, 4: e7247-10.1371/journal.pone.0007247.
Acknowledgements
We would like to thank the patients for their participation in these studies. We thank Fumiko Ozawa for her technical assistance. This work was supported by Grants-in-Aid from the Ministry of Health, Labor, and Welfare of Japan and the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
DOI: 10.1186
Published on: 20110310
Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies
https://medicalgasresearch.biomedcentral.com/articles/10.1186/2045-9912-1-24
Abstract
Background
Molecular hydrogen is important in more than 30 animal models, especially in oxidative stress-mediated diseases and inflammatory diseases. Furthermore, hydrogen effects have been reported in human type 2 diabetes, hemodialysis, metabolic syndrome, radiotherapy for liver cancer, and brainstem infarction. The hydrogen effect has been attributed to specific radical scavenging activities to eliminate hydroxyl radicals and peroxynitrite, as well as signal-modulating activities, but the detailed molecular mechanisms remain elusive. Hydrogen is a safe molecule, mainly produced by gut bacteria in rodents and humans, and no adverse effects have been recorded.
Methods
We conducted an open-label study in 5 patients with progressive muscular dystrophy (PMD), 4 patients with polymyositis/dermatomyositis (PM/DM) and 5 patients with mitochondrial myopathy drinking 1.0 liters of rich daily Hydrogen water for 12 weeks (MM). Serum parameters and 8-isoprostaglandin were measured 18 times in urine every 4 weeks. Next, we conducted a randomized, double-blind, placebo-controlled, crossover study of 0.5 liters of hydrogen-rich water per day or placebo water in 10 patients with DM and 12 patients with MM for 8 weeks with 18 measurements each Serum parameters. 4 weeks.
Results
No objective improvement or worsening of clinical symptoms was observed in the open-label study. However, we observed significant effects on lactate to pyruvate ratios in PMD and MM, fasting blood glucose in PMD, serum matrix metalloproteinase-3 (MMP3) in PM/DM, and serum triglycerides in PM/DM. influences. No objective clinical effect was observed in the double-blind study, but a significant improvement in lactate in MM was noted. The lactate to pyruvate ratio in MM and MMP3 in DM also showed good responses, but not statistically significant. No adverse effects were observed in all studies, except for a hypoglycemic event in one MELAS patient receiving insulin, which was resolved by reducing the insulin dose.
Conclusion
Hydrogen-rich water improves mitochondrial dysfunction in MM and inflammatory processes in PM/DM. The less pronounced effect in the double-blind study may be due to the lower amount of hydrogen administered and the shorter observation period compared to the open-label study, suggesting a threshold or dose-response effect of hydrogen.
References
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. 10.1038/nm1577.
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: 10-10.1186/2045-9912-1-10.
Nakao A, Sugimoto R, Billiar TR, McCurry KR: Therapeutic Antioxidant Medical Gas. J Clin Biochem Nutr. 2009, 44: 1-13. 10.3164/jcbn.08-193R.
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.
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. 10.1016/j.bbrc.2009.09.047.
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. 10.1016/j.nutres.2008.01.008.
Nakayama M, Kabayama S, Nakano H, Zhu WJ, Terawaki H, Nakayama K, Katoh K, Satoh T, Ito S: Biological Effects of Electrolyzed Water in Hemodialysis. Nephron Clin Pract. 2009, 112: C9-C15. 10.1159/000210569.
Nakayama M, Nakano H, Hamada H, Itami N, Nakazawa R, Ito S: A novel bioactive haemodialysis system using dissolved dihydrogen (H-2) produced by water electrolysis: a clinical trial. Nephrol Dial Transplant. 2010, 25: 3026-3033. 10.1093/ndt/gfq196.
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. 10.3164/jcbn.09-100.
Kang K-M, Kang Y-N, Choi I-B, 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: 11-10.1186/2045-9912-1-11.
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: 12-10.1186/2045-9912-1-12.
DiMauro S: Pathogenesis and treatment of mitochondrial myopathies: recent advances. Acta Myologica. 2010, 29: 333-338.
Wei YH, Lu CY, Wei CY, Ma YS, Lee HC: Oxidative stress in human aging and mitochondrial disease-consequences of defective mitochondrial respiration and impaired antioxidant enzyme system. Chin J Physiol. 2001, 44: 1-11.
McKenzie M, Liolitsa D, Hanna MG: Mitochondrial disease: mutations and mechanisms. Neurochem Res. 2004, 29: 589-600.
Sternlicht MD, Werb Z: How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol. 2001, 17: 463-516. 10.1146/annurev.cellbio.17.1.463.
Nishijima C, Hayakawa I, Matsushita T, Komura K, Hasegawa M, Takehara K, Sato S: Autoantibody against matrix metalloproteinase-3 in patients with systemic sclerosis. Clin Exp Immunol. 2004, 138: 357-363. 10.1111/j.1365-2249.2004.02615.x.
Fujita K, Seike T, Yutsudo N, Ohno M, Yamada H, Yamaguchi H, Sakumi K, Yamakawa Y, Kido MA, Takaki A, Katafuchi T, Nakabeppu Y, Noda M: Hydrogen in drinking water reduces dopaminergic neuronal loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. PLoS One. 2009, 4: e7247-10.1371/journal.pone.0007247.
Acknowledgements
We would like to thank the patients for their participation in these studies. We thank Fumiko Ozawa for her technical assistance. This work was supported by Grants-in-Aid from the Ministry of Health, Labor, and Welfare of Japan and the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
