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Emerging Clinical Applications for Molecular Hydrogen.

分子状水素の臨床応用における最新動向：吸入療法を中心としたナラティブレビュー

review inhalation not assessed

Abstract

Molecular hydrogen (H2) has attracted growing interest as a biomedical agent with potential relevance to neurological, cardiovascular, oncological, and respiratory conditions. Preclinical evidence points to selective antioxidant, anti-inflammatory, and cytoprotective mechanisms as the basis for observed benefits. Available clinical data are generally encouraging; however, the field is constrained by small study populations, heterogeneous methodologies, and the lack of standardized delivery systems. This narrative review consolidates existing clinical experience with inhaled H2, examines the principal limitations of the current literature, and outlines priority areas for future investigation, including the validation of delivery platforms that would facilitate broader and more rigorous clinical research.

Mechanism

H2 is proposed to exert its effects through selective scavenging of highly reactive species such as hydroxyl radicals and peroxynitrite, alongside anti-inflammatory and cytoprotective actions that collectively reduce cellular damage.

Bibliographic

Authors
Nguyen Puente B, Habet V, Wheeler CR, Kheir JN
Journal
Respir Care
Year
2026
PMID
41449652
DOI
10.1177/19433654251398759

Tags

Delivery:inhalation delivery (196) Mechanism:antioxidant enzymes (423) hydroxyl radical scavenging (352) anti-inflammatory (743) oxidative stress (899) peroxynitrite scavenging (64) reactive oxygen species (774)

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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