# Molecular hydrogen increases resilience to stress in mice.
> 水素ガス吸入がマウスのストレス耐性に与える影響：うつ・不安様行動および神経内分泌応答の検討


## Abstract

Failure to adapt to stress can precipitate depressive and anxiety disorders. This animal study examined whether repeated inhalation of a hydrogen-oxygen mixed gas (67% H2 : 33% O2 by volume) could modify stress-related behavioral and neuroendocrine responses in mice. Across multiple behavioral assays—tail suspension, forced swimming, novelty-suppressed feeding, and open-field tests—hydrogen-oxygen inhalation significantly reduced both acute and chronic mild stress (CMS)-induced depressive- and anxiety-like behaviors. ELISA measurements revealed that the gas mixture prevented CMS-associated rises in serum corticosterone, adrenocorticotropic hormone, interleukin-6, and tumor necrosis factor-α. Notably, hydrogen exposure during adolescence produced lasting improvements in stress resilience that persisted into early adulthood. The authors propose that suppression of hypothalamic-pituitary-adrenal axis hyperactivation and attenuation of inflammatory signaling underlie these effects.

### Mechanism

Hydrogen gas is proposed to enhance stress resilience by suppressing hypothalamic-pituitary-adrenal axis hyperactivation and reducing pro-inflammatory cytokine levels (IL-6 and TNF-α), thereby dampening both neuroendocrine and inflammatory responses to stress.

## Bibliographic

- **Authors**: Gao Q, Song H, Wang X, Liang Y, Xi YJ, Gao Y, et al.
- **Journal**: Sci Rep
- **Year**: 2017 (2017-08-29)
- **PMID**: [28852144](https://pubmed.ncbi.nlm.nih.gov/28852144/)
- **DOI**: [10.1038/s41598-017-10362-6](https://doi.org/10.1038/s41598-017-10362-6)
- **PMC**: [PMC5575246](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575246/)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: positive
- **H2 concentration**: 67%

## Delivery context

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.

## Safety notes

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information 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)
- [LFL / UFL terminology](https://h2-papers.org/en/safety-notes/lfl-ufl-explained)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 28852144. https://h2-papers.org/en/papers/28852144
> **Source**: PubMed PMID [28852144](https://pubmed.ncbi.nlm.nih.gov/28852144/)