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

Abstract

Molecular hydrogen (H2) demonstrates selective antioxidant and anti-inflam- matory 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 infu- sion - 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.

Study details

Article type

Systematic Review / Meta-Analysis

Disease / injury model

Osteoarthritis, Rheumatoid arthritis, Muscle atrophy, Chronic pain syndromes, Tendinopathies, Exercise-induced muscle damage

Dose comparison

Dose-dependent effects are discussed, with higher doses and longer durations showing more pronounced effects in some clinical trials (e.g., rheumatoid arthritis). Dosage and duration are highlighted as critical for sustained effects.

Dose-dependent effect

Yes

Outcome

Positive

Findings

Molecular hydrogen therapy shows promising antioxidant, anti-inflammatory, and cytoprotective effects in musculoskeletal conditions, with evidence of symptomatic relief in osteoarthritis, reduced disease activity in rheumatoid arthritis, and improved muscle recovery. However, clinical translation is limited by small sample sizes, short durations, protocol heterogeneity, and inconsistent biomarker reporting. H2 is safe and may serve as an adjunctive therapy, but robust, standardized trials are needed for clinical validation.