Precision Antioxidant Supplementation in Physically Active Populations: Sex-Specific Redox Mechanisms and Personalized Approaches

Reactive oxygen species generated during physical exercise have traditionally been regarded as detrimental by-products of aerobic metabolism, contributing to the widespread use of antioxidant supplementation to attenuate oxidative stress, facilitate post-exercise recovery, and improve performance outcomes. Recent systematic reviews and meta-analyses demonstrate considerable heterogeneity in the efficacy of antioxidant interventions. This inconsistency appears to reflect differences in intervention characteristics and study designs, as well as substantial inter-individual biological variability. The present narrative review adopts a multidimensional perspective to examine the biological factors and mechanisms underlying heterogeneous responses to antioxidant supplementation in generally healthy physically active individuals, with particular emphasis on sex-related redox regulation, hormonal influences, baseline redox phenotype, training status, and other modifiers of antioxidant responsiveness. The core evidence comprises 21 publications, including 10 original human studies addressing hormonal status, age, physical activity, and redox-related outcomes, and 11 systematic reviews with or without meta-analysis examining supplementation in exercise settings; additional human and mechanistic evidence informs the narrative synthesis. Collectively, the findings support the rationale for precision antioxidant supplementation that accounts for individual biological characteristics, including sex and hormonal status, as well as exercise context and antioxidant-specific properties. Based on the current mechanistic and human evidence, we propose a conceptual framework in which antioxidant supplementation is tailored to individual biological characteristics, exercise demands, and compound-specific mechanisms while preserving adaptive redox signaling and limiting excessive oxidative stress.