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. 2011 Oct 3;1(1):24.
doi: 10.1186/2045-9912-1-24.

Open-label Trial and Randomized, Double-Blind, Placebo-Controlled, Crossover Trial of Hydrogen-Enriched Water for Mitochondrial and Inflammatory Myopathies

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Free PMC article

Open-label Trial and Randomized, Double-Blind, Placebo-Controlled, Crossover Trial of Hydrogen-Enriched Water for Mitochondrial and Inflammatory Myopathies

Mikako Ito et al. Med Gas Res. .
Free PMC article

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Figures

Figure 1
Figure 1
Temporal profiles of four parameters that demonstrate statistical significance by one-way repeated measures ANOVA in the open-label trial. Ratios of serum lactate/pyruvate (L/P) in 5 mitochondrial myopathies (MM) patients (A) and 4 progressive muscular dystrophy (PMD) patients (B). Note abnormally high L/P ratios in MM patients. (C) Fasting glucose in 4 PMD patients. (D) Serum MMP3 in 5 Polymyositis (PM)/Dermatomyositis (DM) patients. (E) Serum triglycerides in 4 PMD patients. Twelve weeks on HEW are indicated by a box in each panel. Means and SD are plotted. Statistically different values by the Bonferroni's multiple comparison test are indicated by 'a' and 'b' with *p < 0.05 and **p < 0.01. Bonferroni's test reveal no statistical difference between any two values in (D) and (E). Broken lines show a normal range of each parameter.
Figure 2
Figure 2
Temporal profiles of three parameters in the double-blind trial. Serum lactate (A) and L/P ratios (B) in 12 mitochondrial myopathies (MM) patients. (C) Serum MMP3 in 10 dermatomyositis (DM) patients. Patients took HEW or placebo for 8 weeks. Means and SD are plotted. (A) Serum lactate levels in MM are statistically different by two-way repeated measures ANOVA (p < 0.05, Table 1), but the Bonferroni's multiple comparison test reveals no statistical difference between any two values. No statistical difference was observed in L/P ratios (B) and serum MMP3 (C). The normal range of lactate is 0.5-2.2 mmol/l. Normal ranges of the other parameters are indicated in Figure 1.

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