Hydrogen-oxygen mixture inhalation as an adjunctive treatment to home-based exercise in older patients with knee osteoarthritis: an open-label, blinded-endpoint, randomized controlled trial.

Abstract

This randomized controlled trial enrolled 121 elderly patients with knee osteoarthritis (mean age 81.2 years; 80.2% female) and assigned them to either a hydrogen-oxygen (H-O) inhalation group (60 min/day for 2 weeks, alongside a 12-week home-based exercise program) or an exercise-only control group. The primary endpoint, the WOMAC total score, improved significantly from baseline in both groups, but the between-group difference at week 12 was −5.2 (95% CI −12.1 to 1.7; P = 0.140), falling short of statistical significance. A significant group-by-time interaction (P < 0.001) indicated that H-O inhalation produced more pronounced symptom relief during the initial 2-week period. No between-group differences were detected in inflammatory markers (hs-CRP, NLR, PLR, LMR), physical performance tests, SF-36 quality-of-life scores, exercise adherence, or adverse event rates at week 12. The findings suggest a transient benefit of H-O inhalation in the early phase of a combined exercise regimen, without sustained superiority over exercise alone.

Mechanism

Molecular hydrogen is proposed to scavenge reactive oxygen species and suppress inflammatory mediators, thereby reducing oxidative stress and inflammation in articular tissues, which may underlie the transient symptom relief observed in the early intervention phase.