Polyphenol supplementation and skeletal muscle health in older adults: a systematic review of randomized controlled trials

Sarcopenia is a progressive age-related skeletal muscle disorder characterized by the decline of muscle mass and function, driven by mitochondrial dysfunction, oxidative stress, and chronic low-grade inflammation. Polyphenols have been proposed as candidate modulators of these pathways on mechanistic and preclinical grounds, but whether this plausibility translates into measurable structural and functional benefit in clinical trials remains unresolved. A systematic review following PRISMA 2020 guidelines and the Cochrane Handbook (PROSPERO CRD420251183284) was conducted. Eligible studies were randomized controlled trials evaluating polyphenol supplementation in adults aged ≥ 55 years for outcomes related to skeletal muscle mass, strength, or physical function. Risk of bias was assessed using the Cochrane RoB 2 tool, and because a formal meta-analysis was not feasible given the small number of trials and substantial clinical heterogeneity, effect estimates and measures of uncertainty were tabulated alongside a structured direction-of-effect synthesis, following recommended practice for reviews that cannot pool data quantitatively. Six randomized controlled trials were identified; five had reported outcome data and were included in the synthesis, while a sixth remains an ongoing registered protocol with no results yet available and is reported separately. Interventions included quercetin, epicatechin-rich extracts, tea catechins, cocoa flavonoids, and marine-derived polyphenols, with durations ranging from 4 to 24 weeks among completed trials. Muscle strength improved significantly on between-group comparison in two of five completed trials; effects on muscle mass were inconsistent, with one trial showing a significant group-by-time interaction under a combined polyphenol, amino-acid, and exercise intervention, another showing an attenuated loss without a significant between-group difference, and others showing null or less clearly attributable effects; functional and balance outcomes improved in two of three trials that assessed them. Polyphenol supplementation shows biologically plausible but currently inconsistent effects on skeletal muscle outcomes in older adults; the evidence base remains too small, heterogeneous, and methodologically limited to support therapeutic recommendations. Larger, standardized randomized trials in populations with confirmed sarcopenia, incorporating direct neuromuscular assessment, are required before clinical translation.