Complex regional pain syndrome type 1 (CRPS-I) is a devastating complication that can occur after limb extremity injuries. The effectiveness of vitamin C in preventing CRPS-I incidence is debatable. Therefore, we conducted a systematic review and meta-analysis to assess the role of vitamin C in CRPS-I prevention and its effect on pain score, functional outcomes and complications rate after wrist, ankle, and foot fractures.

We searched Medline, Embase, the Cochrane Library, Clinicaltrial.gov, and Google Scholar from infinity to May 2021 for relevant studies comparing the incidence of CRPS-I with administration of perioperative vitamin C versus placebo after wrist, ankle, and foot fractures. Continuous data such as functional outcomes and pain scores were pooled as mean differences (MD), whist dichotomous variables such as the incidence of CRPS-I and complications were pooled as odds ratios (OR), with 95% confidence interval (CI). Data analyses was done using R software (meta package, version 4.9-0) for Windows.

Eight studies, including two quasi-experimental studies, were included. The timeframe for vitamin C administration ranged from 42 to 50 days post-injury and/or surgical fixation and the dosage was either 500 mg or 1000 mg. The results showed that vitamin C was associated with a lower rate of CRPS-I relative to a placebo (OR 0.33, 95% CI [0.17, 0.63]). No significant difference was found between vitamin C and placebo in terms of complications (OR 1.90, 95% CI [0.99, 3.65]), functional outcomes (MD 6.37, 95% CI [-1.40, 14.15]), and pain scores (MD -0.14, 95% CI [-1.07, 0.79]).

The findings demonstrate that when compared to placebo, at least 42 days of vitamin C prophylaxis is associated with prevention of CRPS-I following wrist, ankle, and foot fractures, irrespective of vitamin C dosage or fracture type. No significant differences were found with secondary outcomes.