# Hydrogen-rich water alleviates constipation by attenuating oxidative stress through the sirtuin1/nuclear factor-erythroid-2-related factor 2/heme oxygenase-1 signaling pathway.
> 水素水が便秘に伴う腸管酸化ストレスをSIRT1/Nrf2/HO-1シグナル経路を介して軽減する機序の解明


## Abstract

Using a loperamide-induced constipation model in Sprague-Dawley rats, this study examined the effects of ad libitum hydrogen-rich water (HRW) consumption. HRW improved 24-hour stool output, fecal water content, and charcoal propulsion rate, while restoring intestinal mucus layer thickness, c-kit expression, and enteric neuron counts. 16S rDNA sequencing revealed correction of gut microbiota dysbiosis, and non-targeted serum metabolomics identified associated metabolic abnormalities. Colonic oxidative stress markers (ROS, MDA) were reduced and superoxide dismutase activity was elevated through upregulation of the SIRT1/Nrf2/HO-1 signaling pathway. Intraperitoneal injection of the SIRT1 inhibitor EX527 reversed these benefits, confirming pathway dependence. In NCM460 cells, two identified serum metabolites—β-leucine and traumatic acid—upregulated SIRT1 and attenuated H2O2-induced oxidative stress, suggesting a mechanistic link between HRW-driven metabolite shifts and antioxidant signaling.

### Mechanism

HRW activates SIRT1, which in turn induces Nrf2 and HO-1 expression, reducing colonic ROS and malondialdehyde levels and restoring intestinal motility. Serum metabolites β-leucine and traumatic acid further upregulate SIRT1, reinforcing antioxidant signaling.

## Bibliographic

- **Authors**: Chen KD, Wang K, Chen C, Zhu Y, Tang W, Wang Y, et al.
- **Journal**: World J Gastroenterol
- **Year**: 2024 (2024-05-28)
- **PMID**: [38855154](https://pubmed.ncbi.nlm.nih.gov/38855154/)
- **DOI**: [10.3748/wjg.v30.i20.2709](https://doi.org/10.3748/wjg.v30.i20.2709)
- **PMC**: [PMC11154682](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11154682/)
- **Study type**: animal study
- **Delivery route**: hydrogen-rich water
- **Effect reported**: positive

## 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 38855154. https://h2-papers.org/en/papers/38855154
> **Source**: PubMed PMID [38855154](https://pubmed.ncbi.nlm.nih.gov/38855154/)