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

Table 1 Clinical evidence of hydrogen therapy in osteoarthritis

Ref.	Year	Study design	Participants (number, characteristics, KL grade)	Intervention (method, dose, duration)	Primary outcome (WOMAC score, significance)	Secondary outcomes (inflammation, functional tests, QoL, significance)	Main conclusions (initial vs sustained effects)	Limitations
Wang et al[24]	2025	Open-label, blinded-endpoint, randomized controlled trial	121 elderly KOA patients (average age 812 years, 80.2% female; KL grade 2 or grade 3; KOA duration ≥ 6 months)	H2-O2 inhalation (2.0 L/minute H2, 1.0 L/minute O2) for 60 minute/day over 2 weeks, adjunctive to 12-week HBE program; control: HBE only	WOMAC total score: (1) Group H improved -22.9 from baseline (P < 0.001); (2) Group C improved -19.4 from baseline (P < 0.001); (3) Between-group difference at week-12: -5.2 (P = 0.140), not clinically significant (MCID = 9); and (4) Peak MD at week-2: -8.0 (P = 0.024)	(1) Inflammation (hs-CRP, NLR, PLR, LMR): No significant between-group differences at week-12 (P > 0.4); (2) Functional tests (CST, TUG): No significant between-group differences at week-12 (P > 0.1). Both groups improved from baseline; (3) QoL (SF-36): No significant between-group differences at week-12. Both groups improved from baseline; and (4) Adverse events: Low incidence, no significant difference	H2-O2 inhalation alleviated KOA symptoms and enhanced functional activity during initial 2 weeks. No sustained effects observed at 12 weeks	Open-label design (bias risk); self-reported adherence; no analysis of plasma inflammatory markers; control group did not receive O2 inhalation; limited generalizability (CCRC population)

KL: Kellgren-Lawrence; KOA: Knee osteoarthritis; HBE: Home-based exercise; WOMAC: Western Ontario and McMaster Universities Arthritis Index; MCID: Minimum clinically important difference; MD: Mean difference; QoL: Quality of life; hs-CRP: High-sensitivity C-reactive protein; NLR: Neutrophil-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio; LMR: Lymphocyte-to-monocyte ratio; CST: Chair stand test; TUG: Timed up and go test; SF-36: Short Form 36 Health Survey Questionnaire; CCRC: Continuing care retirement community.