# An H2-infused, nitric oxide-producing functional beverage as a neuroprotective agent for TBIs and concussions.
> 外傷性脳損傷および脳震盪に対する神経保護を目的とした水素含有・一酸化窒素産生機能性飲料の検討


## Abstract

Traumatic brain injuries (TBIs) affect millions annually, with sports-related incidents alone numbering in the millions per year. The underlying pathophysiology encompasses inflammation, oxidative stress, disrupted ion homeostasis, mitochondrial dysfunction, and apoptosis, compounded by reduced cerebral blood flow causing hypoxia and metabolic waste accumulation. Drug delivery across the blood-brain barrier remains a major obstacle to effective intervention. Molecular hydrogen, owing to its small size and nonpolar character, readily crosses the blood-brain barrier and cellular membranes, exerting selective anti-inflammatory, antioxidant, and anti-apoptotic effects through modulation of transcription factors and phosphorylation cascades. Nitric oxide (NO) plays dual roles in TBI: protective at physiological levels but harmful when inducible nitric oxide synthase is overactivated, generating excess inflammation and oxidative/nitrosative damage. Hydrogen has been shown to regulate NO production and metabolism, potentially amplifying beneficial NO signaling while limiting its damaging effects. A hydrogen-enriched, NO-generating functional beverage was evaluated as a candidate neuroprotective adjuvant for TBIs, with preliminary findings suggesting possible benefit.

### Mechanism

Molecular hydrogen modulates transcription factors and protein phosphorylation cascades to exert anti-inflammatory, antioxidant, and anti-apoptotic effects; it also regulates inducible nitric oxide synthase activity, reducing excess NO-driven oxidative and nitrosative stress while preserving beneficial NO signaling.

## Bibliographic

- **Authors**: LeBaron TW, Kharman J, McCullough ML
- **Journal**: J Integr Neurosci
- **Year**: 2021 (2021-09-30)
- **PMID**: [34645100](https://pubmed.ncbi.nlm.nih.gov/34645100/)
- **DOI**: [10.31083/j.jin2003071](https://doi.org/10.31083/j.jin2003071)
- **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 34645100. https://h2-papers.org/en/papers/34645100
> **Source**: PubMed PMID [34645100](https://pubmed.ncbi.nlm.nih.gov/34645100/)