Effects of Molecular Hydrogen Assessed by an Animal Model and a Randomized Clinical Study on Mild Cognitive Impairment

Abstract

Background: Oxidative stress is one of the causative factors in the pathogenesis of neurodegenerative diseases including mild cognitive impairment (MCI) and dementia. We previously reported that molecular hydrogen (H2) acts as a therapeutic and preventive antioxidant. Objective: We assess the effects of drinking H2-water (water infused with H2) on oxidative stress model mice and subjects with MCI. Methods: Transgenic mice expressing a dominant-negative form of aldehyde dehydrogenase 2 were used as a dementia model. The mice with enhanced oxidative stress were allowed to drink H2-water. For a randomized double-blind placebo-controlled clinical study, 73 subjects with MCI drank ~300 mL of H2-water (H2-group) or placebo water (control group) per day, and the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) scores were determined after 1 year. Results: In mice, drinking H2-water decreased oxidative stress markers and suppressed the decline of memory impairment and neurodegeneration. Moreover, the mean lifespan in the H2-water group was longer than that of the control group. In MCI subjects, although there was no significant difference be- tween the H2- and control groups in ADAS-cog score after 1 year, carriers of the apolipoprotein E4 (APOE4) genotype in the H2-group were improved significantly on total ADAS-cog score and word re- call task score (one of the sub-scores in the ADAS-cog score). Conclusion: H2-water may have a potential for suppressing dementia in an oxidative stress model and in the APOE4 carriers with MCI.

Study details

Article type

Original Research

Disease / injury model

Mild Cognitive Impairment (MCI), Dementia, Alzheimer's Disease model (DAL101 mice)

Duration

12 months

Dose-dependent effect

No

Outcome

Positive

Findings

Drinking hydrogen water reduced oxidative stress, suppressed memory impairment and neurodegeneration, and extended mean lifespan in an oxidative stress mouse model. In a clinical trial, hydrogen water significantly improved cognitive scores in APOE4 carriers with mild cognitive impairment, but not in the overall MCI group.