EXPRESS: Molecular Hydrogen in Biomedicine: A Comprehensive Review of Mechanisms, Multi-system Therapeutic Effects, and Emerging Delivery Strategies.

Molecular hydrogen (H2) has attracted increasing interest as a potential therapeutic agent because of its redox-modulating and anti-inflammatory properties. This review summarizes current evidence regarding its biological mechanisms, multisystem effects, and emerging delivery strategies. Experimental studies suggest that H2 may attenuate oxidative injury and inflammatory signaling through both direct interactions with highly reactive species and indirect modulation of pathways involving Nrf2, NF-κB, NLRP3, mitochondrial function, and immune regulation. Protective effects have been reported across cardiovascular, neurological, respiratory, digestive, renal, musculoskeletal, and metabolic disease models. However, the available evidence remains predominantly preclinical, whereas human studies are comparatively limited and heterogeneous. The optimal route of administration, dose, treatment duration, pharmacokinetic profile, and long-term safety and efficacy also remain insufficiently defined. Emerging delivery platforms may improve local retention and controlled release but remain largely experimental. Overall, molecular hydrogen represents a promising adjunctive therapeutic strategy, although further mechanistic validation and well-designed clinical studies are required before routine clinical application.