Effects of Molecular Hydrogen Assessed by an Animal Model and a Randomized Clinical Study on Mild Cognitive Impairment.
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.
['Nishimaki|Kiyomi|K|', 'Asada|Takashi|T|', 'Ohsawa|Ikuroh|I|', 'Nakajima|Etsuko|E|', 'Ikejima|Chiaki|C|', 'Yokota|Takashi|T|', 'Kamimura|Naomi|N|', 'Ohta|Shigeo|S|']
D000284:Administration, Oral D000368:Aged D000071396:Aldehyde Dehydrogenase, Mitochondrial D000818:Animals D000975:Antioxidants D001057:Apolipoproteins E D056547:CA1 Region, Hippocampal D060825:Cognitive Dysfunction D004195:Disease Models, Animal D004311:Double-Blind Method D060766:Drinking Water D005260:Female D006801:Humans D006859:Hydrogen D008297:Male D008606:Mental Processes D008810:Mice, Inbred C57BL D008822:Mice, Transgenic D019636:Neurodegenerative Diseases D018696:Neuroprotective Agents D018384:Oxidative Stress D016896:Treatment Outcome
hydrogen randomized clinical study mild cognitive impairment aldehyde dehydrogenase 2 ADAS-cog score ApoE4 hydrogen water oxidative
stress