Creatine plus β-Hydroxy-β-Methylbutyrate supplementation is associated with preserved glutathione redox-balance and redox–function associations in older adults: a secondary analysis of a randomized crossover trial

Oxidative stress contributes to age-related musculoskeletal decline, partly through disruption of glutathione-dependent redox homeostasis. Although creatine and β-hydroxy-β-methylbutyrate (HMB) have been individually linked to antioxidant and cytoprotective effects, their combined influence on systemic redox balance in older adults remains insufficiently characterized.To examine the effects of creatine plus HMB supplementation on oxidative stress biomarkers and composite redox indices, and to explore whether redox adaptations co-vary with changes in functional measures in physically active older adults.In a randomized, double-blind, placebo-controlled crossover trial, 30 physically active older adults (62.7 ± 5.3 years; 20 men, 10 women) completed two 6-week intervention phases (3 g/day creatine + 3 g/day calcium HMB vs. placebo) during supervised exercise training. Primary endpoints were oxidized glutathione and the Glutathione Redox Index. Secondary biomarkers and composite indices were analyzed with false discovery rate (FDR) control. Percent changes (Δ%) in functional tests were examined exclusively as exploratory correlates of redox adaptations.Supplementation was associated with attenuation of the placebo-related increase in oxidized glutathione and nominal preservation of the Glutathione Redox Index, although these effects did not remain significant after FDR adjustment. In men, a nominal increase in malondialdehyde was observed under supplementation. Exploratory analyses indicated weak associations between changes in composite redox indices and Δ% functional measures.Creatine plus HMB supplementation was associated with nominal modulation of glutathione-centered redox balance during training in active older adults. Exploratory redox-function associations support further investigation in larger, adequately powered trials.