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 between
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 recall
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.