Proanthocyanidins and skeletal muscle health: An integrative systematic review of molecular, preclinical, and clinical evidence

BACKGROUND: Declining skeletal muscle function contributes to physical disability, metabolic disease, and age-related frailty. Proanthocyanidins (PACs), particularly grape seed proanthocyanidin extract (GSPE), have been proposed as candidate interventions because of antioxidant, anti-inflammatory, and metabolic effects. METHODS: Following PRISMA 2020 guidelines, we searched PubMed and Google Scholar for studies published between January 2000 and September 2025 examining the effects of PACs/GSPE on skeletal muscle. Two independent reviewers screened 1245 records and extracted data from eligible studies. RESULTS: Fifteen unique studies met the inclusion criteria: ten animal studies, four in vitro studies, and one randomized controlled trial in humans. Preclinical studies consistently reported favorable effects on oxidative/mitochondrial signaling, muscle-fiber remodeling, glucose handling, and attenuation of oxidative or inflammatory injury markers. The single human trial (54 athletes; OPC 210 mg/day for 9 days) reported a smaller post-exercise CK rise, but it was short, unreplicated, and focused primarily on biochemical surrogate markers rather than functional outcomes. CONCLUSIONS: PACs show mechanistic plausibility for supporting skeletal muscle health in preclinical models. However, clinical efficacy remains unproven because human evidence is limited to one small short-duration RCT, and certainty of evidence was judged very low owing to indirectness and very serious imprecision.