Antioxidant Interventions on Muscle Function and Mass in Aging-Related Muscle Decline: A Systematic Review of Preclinical and Clinical Evidence
TL;DR
Current evidence does not support a consistent increase in muscle quantity with antioxidant interventions, and the observed pattern appears context dependent and requires confirmation in adequately powered, phenotype-stratified trials assessing muscle strength, physical performance, muscle quantity, and mechanistic endpoints.
Abstract
Oxidative stress contributes to aging-related muscle decline, but antioxidant interventions may affect functional and structural outcomes differently. This systematic review synthesized clinical, animal, and cellular evidence across clinically defined sarcopenia and broader models of aging-related muscle decline. PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched through 11 July 2026. Eligible studies tested antioxidant interventions in older adults or aging-related preclinical models and were appraised using the Cochrane Risk of Bias 2 (RoB 2) tool, a modified Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk-of-bias tool, and a modified in vitro checklist. Forty-four publications were included: eight clinical trials, 26 animal datasets, and 18 cellular datasets, with eight publications contributing both animal and cellular evidence. Comparative clinical benefits were reported primarily for strength or power (7/8 studies), with less support for physical performance (2/6 studies assessing this domain) or body composition-related muscle quantity (2/8 studies). Selected preclinical studies likewise showed functional gains without parallel structural improvement, although effects varied by model and intervention. Preclinical findings implicated antioxidant defense, mitochondrial maintenance, inflammation, and proteostasis, but most pathway evidence was associative and direct experimental validation was limited. Clinical evidence was further constrained by small samples, short interventions, combined nutritional or exercise co-interventions, and heterogeneous outcomes. Current evidence does not support a consistent increase in muscle quantity with antioxidant interventions. The observed pattern appears context dependent and requires confirmation in adequately powered, phenotype-stratified trials assessing muscle strength, physical performance, muscle quantity, and mechanistic endpoints.