# Neuroprotective and Preventative Effects of Molecular Hydrogen.
> 分子状水素の神経保護および神経疾患予防効果に関するレビュー


## Abstract

This review examines the neuroprotective capacity of molecular hydrogen (H₂) and its potential relevance to neurodegenerative conditions such as Parkinson's and Alzheimer's diseases, for which disease-modifying pharmacological options remain limited. Multiple mechanisms are discussed, including suppression of reactive oxygen species (ROS)—encompassing both hydroxyl radicals and superoxide—anti-inflammatory signaling, and endocrine regulation through the gut-brain axis. In Parkinson's disease model mice, sustained H₂ intake was associated with increased ghrelin secretion from the stomach. In Alzheimer's disease model mice, sex-dependent neuroprotection was observed: female mice showed preservation of estrogen and estrogen receptor-β (ERβ) levels, accompanied by upregulation of brain-derived neurotrophic factor (BDNF) and its receptor TrkB. The precise molecular targets through which H₂ modulates endocrine pathways and exerts these effects remain to be identified, representing a key direction for future research.

### Mechanism

H₂ suppresses ROS generation including hydroxyl radicals and superoxide, exerts anti-inflammatory effects, and modulates the gut-brain endocrine axis by promoting ghrelin release and preserving estrogen/ERβ levels, thereby upregulating BDNF and TrkB expression in neural tissue.

## Bibliographic

- **Authors**: Noda M, Liu J, Long J
- **Journal**: Curr Pharm Des
- **Year**: 2021
- **PMID**: [33076798](https://pubmed.ncbi.nlm.nih.gov/33076798/)
- **DOI**: [10.2174/1381612826666201019103020](https://doi.org/10.2174/1381612826666201019103020)
- **Study type**: review
- **Delivery route**: hydrogen-rich water
- **Effect reported**: not assessed

## 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 33076798. https://h2-papers.org/en/papers/33076798
> **Source**: PubMed PMID [33076798](https://pubmed.ncbi.nlm.nih.gov/33076798/)