Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies.
Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies.
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DOI：
10.1186/2045-9912-1-24
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发表时间：
2011-10-03
影响因子：
2.9
通讯作者：
Ohno K
中科院分区：
文献类型：
--
作者：
Ito M;Ibi T;Sahashi K;Ichihara M;Ito M;Ohno K
分子氢在30多种动物模型中特别是氧化应激介导的疾病和炎性疾病中具有显著的作用。此外，氢对人类的影响已在2型糖尿病、血液透析、代谢综合征、肝癌放疗和脑干梗死中报道。氢效应归因于消除羟自由基和过氧亚硝酸根的特定自由基清除活性，以及信号调节活性，但详细的分子机制仍然难以捉摸。氢是一种安全的分子，主要由啮齿动物和人类的肠道细菌产生，没有记录显示有任何不良影响。我们对5例进行性肌营养不良症（PMD）、4例多发性肌炎/皮肌炎（PM/DM）和5例线粒体肌病（MM）患者进行了12周每天饮用1.0升富氢水的开放标签试验，并每4周测量18项血清参数以及尿8-异前列腺素。接下来，我们在10名DM患者和12名MM患者中进行了一项随机、双盲、安慰剂对照、交叉试验，每天饮用0.5升富氢水或安慰剂水，持续8周，每4周测量18项血清参数。在开放标签试验中，未观察到临床症状的客观改善或恶化。然而，我们观察到PMD和MM的乳酸/丙酮酸比值、PMD的空腹血糖、PM/DM的血清基质金属蛋白酶3（MMP 3）和PM/DM的血清甘油三酯的显著影响。在双盲试验中，没有观察到客观的临床效果，但在MM中检测到乳酸的显著改善。MM中的乳酸-丙酮酸比和DM中的MMP 3也表现出有利的反应，但没有统计学意义。除1例接受胰岛素治疗的MELAS患者发生低血糖事件外，两项试验均未观察到不良反应，该事件通过减少胰岛素剂量而消退。富氢水改善MM的线粒体功能障碍和PM/DM的炎症过程。与开放标签试验相比，双盲试验的影响不太突出，可能是由于氢的给药量较低和观察期较短，这意味着氢的阈值效应或剂量反应效应。
Molecular hydrogen has prominent effects on more than 30 animal models especially of oxidative stress-mediated diseases and inflammatory diseases. In addition, hydrogen effects on humans have been reported in diabetes mellitus type 2, hemodialysis, metabolic syndrome, radiotherapy for liver cancer, and brain stem infarction. Hydrogen effects are ascribed to specific radical-scavenging activities that eliminate hydroxyl radical and peroxynitrite, and also to signal-modulating activities, but the detailed molecular mechanisms still remain elusive. Hydrogen is a safe molecule that is largely produced by intestinal bacteria in rodents and humans, and no adverse effects have been documented. We performed open-label trial of drinking 1.0 liter per day of hydrogen-enriched water for 12 weeks in five patients with progressive muscular dystrophy (PMD), four patients with polymyositis/dermatomyositis (PM/DM), and five patients with mitochondrial myopathies (MM), and measured 18 serum parameters as well as urinary 8-isoprostane every 4 weeks. We next conducted randomized, double-blind, placebo-controlled, crossover trial of 0.5 liter per day of hydrogen-enriched water or placebo water for 8 weeks in 10 patients with DM and 12 patients with MM, and measured 18 serum parameters every 4 weeks. In the open-label trial, no objective improvement or worsening of clinical symptoms was observed. We, however, observed significant effects in 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. In the double-blind trial, no objective clinical effects were observed, but a significant improvement was detected in lactate in MM. Lactate-to-pyruvate ratios in MM and MMP3 in DM also exhibited favorable responses but without statistical significance. No adverse effect was observed in either trial except for hypoglycemic episodes in an insulin-treated MELAS patient, which subsided by reducing the insulin dose. Hydrogen-enriched water improves mitochondrial dysfunction in MM and inflammatory processes in PM/DM. Less prominent effects with the double-blind trial compared to the open-label trial were likely due to a lower amount of administered hydrogen and a shorter observation period, which implies a threshold effect or a dose-response effect of hydrogen.