Vitamin C and Reduced Complex Regional Pain Syndrome

Research synthesisLow evidenceSmall effect3 studies · 3 beneficial · 0 neutral · 0 harmful

Across 3 studies, all reported small beneficial effects of vitamin C on reducing complex regional pain syndrome (CRPS). Evidence comes primarily from clinical populations undergoing total knee arthroplasty, with a median study duration of 40 days. The most-studied dose was 1 g daily, though this was reported in only one study.

Effective dose range: 1 g daily
Studied populations: patients undergoing total knee arthroplasty (TKA), adults with chronic neuropathic pain

Caveats: Evidence base is small (only 3 studies) — conclusions should be considered preliminary. Available evidence is overwhelmingly positive — clinical literature in this area is subject to publication bias (null-result studies are less likely to be published or indexed). The effect size was small across all studies, and the largest study (n=960) reported an odds ratio of 0.59, suggesting a modest reduction in risk.

Generated Jul 11, 2026

Doses used in studies

g/day: 1 (median 1, IQR 1–1) — 1 study

Time to effect

Median: 5.7 weeks · IQR 5.7 weeks–5.7 weeks · Range 5.7 weeks–5.7 weeks — Reported in 1 of 3 studies

Safety in these studies

Overall tolerabilityReported
No major safety concerns were identified.
from: The Role of Vitamin C Supplementation in Total Knee Arthroplasty Outcomes: A Systematic Re

3 of 3 papers

The role of diet and non-pharmacologic supplements in the treatment of chronic neuropathic pain: A systematic review.
- 2023-08-31
- Systematic Review
- Pain practice : the official journal of World Institute of Pain 24(1)
- - Jennifer K Frediani
  - Asim A Lal
  - Esther Kim
  - Sharon L Leslie
  - David W Boorman
  - Vinita Singh
- PubMed: 37654090
- DOI: 10.1111/papr.13291
5 Insights on
- Reduced Complex Regional Pain Syndrome
- High evidence
- Clinical
The early use of vitamin C prophylaxis for the development of CRPS-I also seems promising.
Effect
Beneficial
Effect size
Small
Significant
Yes
The Role of Vitamin C Supplementation in Total Knee Arthroplasty Outcomes: A Systematic Review of Randomized Controlled Trials.
- 2026-01-01
- Review · n = 364
- 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
5 Insights on
- Reduced Complex Regional Pain Syndrome
- High evidence
- Clinical
Evidence for reduced complex regional pain syndrome (CRPS) was more consistent but still limited by small sample sizes.
Effect
Beneficial
Effect size
Small
Significant
Yes
Prophylaxis Against Complex Regional Pain Syndrome Recurrence with Vitamin C in Total Knee Arthroplasty: A Propensity Score-Matched Analysis of 960 Cases.
- 2025-09-09
- Observational · n = 960
- The Journal of bone and joint surgery. American volume 107(21)
- - Jacques Hernigou
  - Esfandiar Chahidi
  - Johnatan Everaert
  - Liam Sabot
  - Alexandre Hupez
  - Gauthier Gamela Sedieto
  - Antoine Callewier
  - Olivier Bath
  - Sagi Martinov
  - Sagi Martinov
- PubMed: 40924823
- DOI: 10.2106/jbjs.24.01584
2 Insights on
- Reduced Complex Regional Pain Syndrome
- High evidence
- Clinical
In the PSM population, 6.9% (33) of the 480 patients who received vitamin C prophylaxis after TKA developed CRPS compared with 11.0% (53) of the 480 who did not receive vitamin C (odds ratio [OR] = 0.59 [95% confidence interval (CI), 0.37 to 0.9], p = 0.024).
Effect
Beneficial
Effect size
Small
Significant
Yes
Dose
1 g daily for 40 days

Vitamin C and Reduced Complex Regional Pain Syndrome

The role of diet and non-pharmacologic supplements in the treatment of chronic neuropathic pain: A systematic review.

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

Prophylaxis Against Complex Regional Pain Syndrome Recurrence with Vitamin C in Total Knee Arthroplasty: A Propensity Score-Matched Analysis of 960 Cases.