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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

human randomized controlled trial inhalation null 6.5%

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
DOI
10.1007/s10072-021-05489-4
PMC
PMC8519836

Tags

Delivery context

In air, molecular hydrogen is reported to be combustible across approximately **4% (LFL, lower flammability limit) to 75% (UFL, upper flammability limit)**. Among high-concentration hydrogen inhalers, 66% output sits inside this range, and even pure-hydrogen (100%) output forms a 4–75% concentration-gradient layer at the device–air boundary (the UFL 75% paradox). Engineering principle would therefore call for operation below LFL (the classical 4%); that figure, however, was measured under closed, pre-mixed, static conditions. For the open, dynamic inhalation environment, the empirical value reported in the literature is **10%**, which is the figure referenced in practice as the operating ceiling. The 66% / 100% output devices are recorded in the Japanese Consumer Affairs Agency accident-information database, and from these considerations are not recommended.

→ Evidence by delivery route

Safety notes

In air, molecular hydrogen is reported to be combustible across approximately **4% (LFL, lower flammability limit) to 75% (UFL, upper flammability limit)**. Among high-concentration hydrogen inhalers, 66% output sits inside this range, and even pure-hydrogen (100%) output forms a 4–75% concentration-gradient layer at the device–air boundary (the UFL 75% paradox). Engineering principle would therefore call for operation below LFL (the classical 4%); that figure, however, was measured under closed, pre-mixed, static conditions. For the open, dynamic inhalation environment, the empirical value reported in the literature is **10%**, which is the figure referenced in practice as the operating ceiling. The 66% / 100% output devices are recorded in the Japanese Consumer Affairs Agency accident-information database, and from these considerations are not recommended.

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