Neuroprotective and Preventative Effects of Molecular Hydrogen

Abstract

One of the beneficial effects of molecular hydrogen (H2, hydrogen gas) is neuroprotection and pre- vention of neurological disorders. It is important and useful if taking H2 every day can prevent or ameliorate the progression of neurodegenerative disorders, such as Parkinson’s disease or Alzheimer’s disease, both lacking specific therapeutic drugs. There are several mechanisms of how H2 protects neuronal damage. Anti-oxidative, anti-inflammatory, and the regulation of the endocrine system via stomach-brain connection seem to play an im- portant role. At the cellular and tissue level, H2 appears to prevent the production of reactive oxygen species (ROS), and not only hydroxy radical (•OH) but also superoxide. In Parkinson’s disease model mice, chronic in- take of H2 causes the release of ghrelin from the stomach. In Alzheimer’s disease model mice, sex-different neu- roprotection is observed by chronic intake of H2. In female mice, declines of estrogen and estrogen receptor-β (ERβ) are prevented by H2, upregulating brain-derived neurotrophic factor (BDNF) and its receptor, tyrosine ki- nase receptor B (TrkB). The question of how drinking H2 upregulates the release of ghrelin or attenuates the de- cline of estrogen remains to be investigated and the mechanism of how H2 modulates endocrine systems and the fundamental question of what or where is the target of H2 needs to be elucidated for a better understanding of the effects of H2.

Study details

Article type

Review

Disease / injury model

Parkinson’s disease model mice, Alzheimer’s disease model mice (including transgenic and MPTP-induced models)

Dose comparison

Chronic intake (e.g., one week or three months) of saturated H2-water is necessary for neuroprotective effects; single or short-term administration is not effective.

Dose-dependent effect

Yes

Outcome

Positive

Findings

Molecular hydrogen (H2) shows neuroprotective and preventative effects against neurodegenerative disorders such as Parkinson’s and Alzheimer’s disease, primarily through anti-oxidative, anti-inflammatory, and endocrine-modulating mechanisms. Chronic intake of H2, especially via drinking H2-water, prevents neuronal damage, reduces oxidative stress, modulates microglial activation, increases ghrelin and estrogen signaling, and provides sex-dependent neuroprotection, particularly in female Alzheimer’s model mice.