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.