Molecular hydrogen therapy in musculoskeletal conditions: An evidence-based review and critical analysis

Molecular hydrogen (H₂) demonstrates selective antioxidant and anti-inflammatory properties with therapeutic potential across musculoskeletal conditions including osteoarthritis, rheumatoid arthritis, exercise-induced muscle damage, chronic pain syndromes, tendinopathies, and muscle atrophy. This review critically evaluates preclinical and clinical evidence for H₂ therapy and identifies research gaps. A comprehensive search of PubMed, EMBASE, and Cochrane Library (up to April 2025) yielded 45 eligible studies: 25 preclinical and 20 clinical trials. Preclinical models consistently showed reductions in reactive oxygen species, inflammatory cytokines, and improved cell viability. Clinical trials reported symptomatic relief in osteoarthritis, decreased Disease Activity Score 28 in rheumatoid arthritis, and accelerated clearance of muscle damage markers. Delivery methods varied - hydrogen-rich water, gas inhalation, and saline infusion - hindering direct comparison. Mechanistic biomarkers were inconsistently reported, limiting understanding of target engagement. Common limitations included small sample sizes, short durations, and protocol heterogeneity. Despite these constraints, findings suggest H₂ may serve as a promising adjunctive therapy via antioxidant, anti-inflammatory, and cytoprotective mechanisms. Future research should prioritize standardized delivery protocols, robust mechanistic endpoints, and longer-term randomized trials to validate clinical efficacy and optimize therapeutic strategies.