# Hydrogen-rich water improves cognitive impairment gender-dependently in APP/PS1 mice without affecting Aβ clearance.
> 水素水投与がAPP/PS1マウスの認知機能障害を性差依存的に改善するが、Aβ除去には影響しない


## Abstract

This animal study examined the effects of hydrogen-rich water administered over 3 months to APPswe/PS1dE9 transgenic mice, a model of Alzheimer's disease. Cognitive behavior improved significantly in female transgenic mice but not in males, without any detectable change in amyloid-beta clearance. In female mice, brain estrogen levels and the expression of estrogen receptor beta (ERβ) and brain-derived neurotrophic factor (BDNF), which were reduced in the transgenic model, were restored by hydrogen-rich water. Suppression of oxidative stress and neuroinflammation was also more pronounced in female brains than in male brains. These findings indicate a sex-specific mechanism of action involving the estrogen–ERβ–BDNF signaling axis in Alzheimer's disease pathogenesis.

### Mechanism

Hydrogen-rich water is proposed to restore brain estrogen levels and upregulate ERβ and BDNF expression, thereby suppressing oxidative stress and neuroinflammation through the estrogen–ERβ–BDNF signaling pathway, producing cognitive benefits specifically in female mice.

## Bibliographic

- **Authors**: Hou C, Peng Y, Qin C, Fan F, Liu J, Long J
- **Journal**: Free Radic Res
- **Year**: 2018
- **PMID**: [29683360](https://pubmed.ncbi.nlm.nih.gov/29683360/)
- **DOI**: [10.1080/10715762.2018.1460749](https://doi.org/10.1080/10715762.2018.1460749)
- **Study type**: animal study
- **Delivery route**: hydrogen-rich water
- **Effect reported**: mixed

## Delivery context

Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

## Safety notes

Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 29683360. https://h2-papers.org/en/papers/29683360
> **Source**: PubMed PMID [29683360](https://pubmed.ncbi.nlm.nih.gov/29683360/)