The Impact of Vitamin C on Analgesic, Anti-inflammatory, and Hemostatic Outcomes After Total Hip and Knee Arthroplasty: A Systematic Review and Meta-Analysis.

Abstract

<h4>Objectives</h4>Vitamin C has anti-inflammatory, antioxidant, and analgesic properties, yet its specific impact on perioperative and postoperative outcomes after total hip and knee arthroplasty remains unclear.<h4>Methods</h4>A PRISMA-compliant, PROSPERO-registered systematic review and meta-analysiss was conducted. Randomized controlled trials (RCTs) evaluating oral or intravenous vitamin C in primary hip or knee arthroplasty were searched in MEDLINE, Embase, Web of Science, and Scopus up to May 2025.Risk of bias was evaluated using the Cochrane RoB tool. Meta-analyses were performed with RevMan version 5.4.1. Effect sizes were expressed as weighted mean differences (WMDs) with 95% confidence intervals (CIs). The certainty of evidence was assessed using the GRADE approach. Statistical heterogeneity was examined using the I² statistic (I² ≥ 50% indicating substantial heterogeneity) and the chi-square test. A fixed-effect model was applied when I² < 50%; otherwise, a random-effects model based on the DerSimonian and Laird method was used.<h4>Results</h4>Of 4,776 records, 3,585 titles/abstracts were screened and 19 full texts assessed; ten RCTs (n=1,162) met inclusion for qualitative synthesis, and three were pooled quantitatively. Vitamin C administration significantly reduced total morphine use after surgery (WMD = -1.41 mg; 95% CI [-2.32, -0.50]; P = 0.002; I² = 0%). It also lowered C-reactive protein (CRP) levels (WMD = -11.32 mg/L; P = 0.0007) and interleukin-6 (IL-6) concentrations (WMD = -8.27 pg/mL; P < 0.0001) at 24 hours, although these effects diminished by 48 hours. No significant differences in postoperative pain scores were observed at either 24 or 48 hours.<h4>Conclusion</h4>This review indicates that vitamin C may be associated with reduced opioid consumption, attenuation of inflammatory responses, and decreased perioperative blood loss among patients undergoing joint arthroplasty. However, the overall strength of evidence remains limited due to heterogeneity in dosage, timing, and routes of administration across the included studies.