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.

Creatine plus HMB supplementation was associated with attenuation of the placebo-related increase in oxidized glutathione, though this effect did not remain significant after false discovery rate adjustment.

• Randomized, double-blind, placebo-controlled crossover trial with 30 physically active older adults (62.7 ± 5.3 years; 20 men, 10 women)
• Two 6-week intervention phases: 3 g/day creatine + 3 g/day calcium HMB vs. placebo during supervised exercise training
• Oxidized glutathione was a primary endpoint
• The placebo condition was associated with an increase in oxidized glutathione that was nominally attenuated under supplementation
• The effect did not survive false discovery rate (FDR) correction

Supplementation was associated with nominal preservation of the Glutathione Redox Index, which also did not remain significant after FDR adjustment.

• The Glutathione Redox Index was a co-primary endpoint alongside oxidized glutathione
• FDR control was applied to secondary biomarkers and composite indices
• Preservation of the Glutathione Redox Index was described as 'nominal'
• Results suggest a trend toward maintained redox homeostasis under supplementation but without statistical robustness after correction

In men, a nominal increase in malondialdehyde was observed under supplementation.

• Malondialdehyde is a marker of lipid peroxidation and oxidative stress
• This sex-specific finding was observed only in the male subgroup (n = 20 men)
• The increase was described as 'nominal,' indicating it did not survive FDR correction
• This finding was among secondary biomarkers analyzed with FDR control

Exploratory analyses indicated weak associations between changes in composite redox indices and percent changes in functional measures.

• Percent changes (Δ%) in functional tests were examined exclusively as exploratory correlates of redox adaptations
• Associations between composite redox indices and functional measures were characterized as 'weak'
• These analyses were exploratory in nature and not primary or confirmatory endpoints
• Results were interpreted as supporting further investigation rather than establishing definitive redox-function relationships

The study population consisted of physically active older adults participating in supervised exercise training during both intervention phases.

• 30 participants with mean age 62.7 ± 5.3 years; 20 men and 10 women
• Participants were described as 'physically active older adults'
• Each intervention phase lasted 6 weeks with supervised exercise training
• Crossover design allowed participants to serve as their own controls across both supplementation and placebo conditions

Oxidative stress was identified as a contributor to age-related musculoskeletal decline through disruption of glutathione-dependent redox homeostasis.

• The rationale for combining creatine and HMB was their individual links to antioxidant and cytoprotective effects
• Their combined influence on systemic redox balance in older adults was described as 'insufficiently characterized' prior to this study
• Glutathione-dependent redox homeostasis was the mechanistic focus of the trial