# Randomized double-blind placebo-controlled trial of hydrogen inhalation for Parkinson's disease: a pilot study.
> パーキンソン病患者を対象とした水素ガス吸入の二重盲検プラセボ対照ランダム化パイロット試験


## Abstract

Oxidative stress is implicated in Parkinson's disease (PD) progression, and animal studies have suggested antioxidant properties of molecular hydrogen. This randomized, double-blind, placebo-controlled parallel-group pilot study enrolled 20 Japanese PD patients receiving levodopa. Participants inhaled 6.5 vol% hydrogen gas at 2 L/min for 1 hour twice daily over 16 weeks; a placebo air group served as control. Five participants were excluded for insufficient total inhalation duration (less than 112 hours). The primary endpoint—change in MDS-UPDRS total score from baseline to week 16—showed no statistically significant difference between groups (Mann-Whitney U test, p > 0.05). No adverse events were recorded. Protocol adherence declined among older participants, those on higher levodopa doses, and those with higher PDQ-39 emotional subscores. The study concluded that hydrogen gas inhalation at this regimen was safe but did not demonstrate measurable clinical benefit in PD.

### Mechanism

Molecular hydrogen is proposed to act as a selective antioxidant, potentially reducing oxidative stress implicated in PD neurodegeneration. Animal model evidence supported this mechanism, but the present clinical pilot did not demonstrate a significant effect on disease rating scores.

## Bibliographic

- **Authors**: Yoritaka A, Kobayashi Y, Hayashi T, Saiki S, Hattori N
- **Journal**: Neurol Sci
- **Year**: 2021
- **PMID**: [34319514](https://pubmed.ncbi.nlm.nih.gov/34319514/)
- **DOI**: [10.1007/s10072-021-05489-4](https://doi.org/10.1007/s10072-021-05489-4)
- **PMC**: [PMC8519836](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8519836/)
- **Study type**: human randomized controlled trial
- **Delivery route**: inhalation
- **Effect reported**: null
- **H2 concentration**: 6.5%

## 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 34319514. https://h2-papers.org/en/papers/34319514
> **Source**: PubMed PMID [34319514](https://pubmed.ncbi.nlm.nih.gov/34319514/)