The Role of Vitamin C Supplementation in Total Knee Arthroplasty Outcomes: A Systematic Review of Randomized Controlled Trials

Document Type : SYSTEMATIC REVIEW

Authors

1 Department of Orthopedics and Trauma Surgery, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

2 Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences

3 Department of Orthopedics and Trauma Surgery, Shariati Hospital, Tehran University of Medical Sciences, Iran

10.22038/abjs.2025.92058.4177

Abstract

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 2025, following PRISMA 2020 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 2). Owing to heterogeneity in dosing, timing, and outcomes, results were synthesized narratively.
Results: Ten RCTs involving 1,364 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

Keywords

Main Subjects

References

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The Archives of Bone and Joint Surgery
Volume 14, Issue 3
March 2026
Pages 170-178

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History

  • Receive Date: 24 October 2025
  • Revise Date: 13 December 2025
  • Accept Date: 14 December 2025

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