Objectives: Oxidative stress, inflammation, and endothelial dysfunction contribute to perioperative morbidity following total knee arthroplasty (TKA).
Vitamin C (ascorbic acid), an essential antioxidant cofactor, has been proposed to mitigate these pathways. This systematic review evaluates current evidence on perioperative vitamin C supplementation in TKA and its effects on pain, inflammation, blood loss, and postoperative recovery. Methods: A systematic search of PubMed, Embase, Scopus, and Web of Science was conducted from database inception through July ۲۰۲۵, following PRISMA ۲۰۲۰ guidelines. Randomized controlled trials (RCTs) assessing perioperative vitamin C use in primary TKA were included. Methodologic quality was appraised using the Cochrane Risk-of-Bias tool (RoB ۲). Owing to heterogeneity in dosing, timing, and outcomes, results were synthesized narratively. Results: Ten RCTs involving ۱,۳۶۴ patients met the inclusion criteria.
Vitamin C administration varied substantially in dose, route, and timing. Across studies, findings for postoperative pain, inflammatory markers, blood loss, and functional recovery were inconsistent. Several reported numerical trends favors vitamin C, but most outcomes lacked statistical significance or were supported by a single study. Evidence for reduced complex regional pain syndrome (CRPS) was more consistent but still limited by small sample sizes. No major safety concerns were identified. Conclusion: Current evidence does not support a definitive benefit of perioperative vitamin C supplementation in TKA. While isolated studies suggest potential reductions in inflammation, blood loss, or pain, these findings are not consistent across trials and often lack statistical significance. Larger, methodologically sound RCTs with standardized dosing protocols are needed before recommending vitamin C as a routine perioperative supplement. Level of evidence: II
