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

2026-01-01
The archives of bone and joint surgery 14(3)
- Fardis Vosoughi
- Golnaz Nikeghbalii
- Mohammadhasan Sharafi
- Ehsan Najafi
- Iman Menbari Oskouie

PubMed: 42137519
DOI: 10.22038/abjs.2025.92058.4177

Study Design

Type: Review
Sample size: n = 364
Population: 1,364 patients undergoing primary total knee arthroplasty
Methods: Systematic search of PubMed, Embase, Scopus, and Web of Science from database inception through July 2025, following PRISMA 2020 guidelines; randomized controlled trials (RCTs) assessing perioperative vitamin C use in primary TKA were included; narrative synthesis due to heterogeneity

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.

Research Insights

Vitamin C→Improved Functional Recovery
Across studies, findings for postoperative pain, inflammatory markers, blood loss, and functional recovery were inconsistent.
Effect
Neutral
Effect size
Small
Vitamin C→Reduced Blood Loss
Across studies, findings for postoperative pain, inflammatory markers, blood loss, and functional recovery were inconsistent.
Effect
Neutral
Effect size
Small
Vitamin C→Reduced Complex Regional Pain Syndrome
Evidence for reduced complex regional pain syndrome (CRPS) was more consistent but still limited by small sample sizes.
Effect
Beneficial
Effect size
Small
Vitamin C→Reduced Inflammation
Across studies, findings for postoperative pain, inflammatory markers, blood loss, and functional recovery were inconsistent.
Effect
Neutral
Effect size
Small
Vitamin C→Reduced Postoperative Pain
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.
Effect
Neutral
Effect size
Small

Adverse Events Reported

Vitamin C→Overall tolerability
No major safety concerns were identified.
Finding
Reported