# Beneficial biological effects and the underlying mechanisms of molecular hydrogen - comprehensive review of 321 original articles.
> 分子状水素の有益な生物学的効果とその作用機序：321報の原著論文に基づく包括的レビュー


## Abstract

Since 2007, research into the biological effects of molecular hydrogen has expanded rapidly across numerous disease models and clinical conditions. By June 2015, a total of 321 original papers had been published, with contributions predominantly from Japan, China, and the United States. Approximately three-quarters of these studies used rodent models, while the number of human clinical investigations has grown annually. Hydrogen-rich water administered ad libitum and hydrogen gas at concentrations below 4% via inhalation represent the most common delivery approaches, with hydrogen-rich saline used for confirmatory experiments. Effects have been documented across 31 disease categories encompassing 166 distinct models, with oxidative stress- and inflammation-related conditions being especially prominent. Beyond selective scavenging of hydroxyl radicals and peroxynitrite, mechanistic studies indicate that hydrogen modulates the activity and expression of signaling molecules including Lyn, ERK, p38, JNK, ASK1, Akt, GTP-Rac1, iNOS, Nox1, NF-κB p65, IκBα, STAT3, NFATc1, c-Fos, and ghrelin. The identity of upstream master regulators coordinating these changes remains under active investigation.

### Mechanism

Molecular hydrogen selectively neutralizes hydroxyl radicals and peroxynitrite, and additionally modulates the activity or expression of multiple signaling molecules—including Lyn, ERK, p38, JNK, ASK1, Akt, NF-κB p65, STAT3, and ghrelin—thereby exerting antioxidant and anti-inflammatory effects through diverse intracellular pathways.

## Bibliographic

- **Authors**: Ichihara M, Sobue S, Ito M, Hirayama M, Ohno K
- **Journal**: Med Gas Res
- **Year**: 2015
- **PMID**: [26483953](https://pubmed.ncbi.nlm.nih.gov/26483953/)
- **DOI**: [10.1186/s13618-015-0035-1](https://doi.org/10.1186/s13618-015-0035-1)
- **PMC**: [PMC4610055](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4610055/)
- **Study type**: review
- **Delivery route**: mixed routes
- **Effect reported**: not assessed
- **H2 concentration**: 4%

## Delivery context

This study combines multiple delivery routes. As a general principle, the most efficient route for routine hydrogen intake is inhalation. Inhalation carries explosion risk (empirical LFL of 10%; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

## Safety notes

This study combines multiple delivery routes. As a general principle, the most efficient route for routine hydrogen intake is inhalation. Inhalation carries explosion risk (empirical LFL of 10%; 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 26483953. https://h2-papers.org/en/papers/26483953
> **Source**: PubMed PMID [26483953](https://pubmed.ncbi.nlm.nih.gov/26483953/)