Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies

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.

Study details

Article type

Original Research

Disease / injury model

Mitochondrial myopathies, Polymyositis/Dermatomyositis, Progressive muscular dystrophy

Duration

12 weeks

Dose comparison

The study compared two different doses of hydrogen-enriched water (1.0 L/day in the open-label trial and 0.5 L/day in the double-blind trial) and found more prominent effects with the higher dose and longer duration, suggesting a dose-response or threshold effect.

Dose-dependent effect

Yes

Outcome

Positive

Findings

Hydrogen-enriched water improved mitochondrial dysfunction in mitochondrial myopathies (MM) and inflammatory processes in polymyositis/dermatomyositis (PM/DM). Significant improvements were observed in lactate-to-pyruvate ratios, fasting blood glucose, serum MMP3, and triglycerides in the open-label trial. In the double-blind trial, a significant improvement was detected in lactate in MM. No objective clinical improvement or worsening was observed, and no adverse effects except for hypoglycemia in one patient, which resolved with insulin adjustment.