Vitamin C in the prevention of Complex Regional Pain Syndrome (CRPS) after surgery or fracture
Näytönastekatsaukset
3.3.2026
Level of evidence: C
Vitamin C supplement may decrease incidence of CRPS after orthopedic surgery or fractures.
The evidence was limited by inconsistency and indirect outcomes. At 12 months follow-up, with 5% prevalence of CRPS, C vitamin supplement could lead to about 2,7% absolute reduction in the incidence (27 less per 1000 patients treated with c-vitamin).
The harms were not assessed but are likely small.
| Reference | Study type | Population | Intervention and comparison | Outcomes | Risk of bias |
|---|---|---|---|---|---|
| RCT=randomized controlled trial; SR=systematic review; MA=meta-analysis | |||||
| «Seth I, Bulloch G, Seth N, et al. Effect of Perioperative Vitamin C on the Incidence of Complex Regional Pain Syndrome: A Systematic Review and Meta-Analysis. J Foot Ankle Surg 2022;61(4):748-754 »1 | SR/MA | Patients undergoing ankle, foot, wrist, and distal radius surgeries | Vitamin C (500/1000 mg per os per day for 42 to 50 days) vs placebo | Incidence of CRPS type 1 | High |
| «Aïm F, Klouche S, Frison A, et al. Efficacy of vitamin C in preventing complex regional pain syndrome after wrist fracture: A systematic review and meta-analysis. Orthop Traumatol Surg Res 2017;103(3)»2 | SR/MA of RCTs | Patients with wrist fracture, treated either conservatively or operatively | Vitamin C (200, 500, or 1500 mg per os per day for 50 days) vs placebo | Incidence of CRPS type 1 at 12 months | Low |
| Reference | Comments |
|---|---|
| «Seth I, Bulloch G, Seth N, et al. Effect of Perioperative Vitamin C on the Incidence of Complex Regional Pain Syndrome: A Systematic Review and Meta-Analysis. J Foot Ankle Surg 2022;61(4):748-754 »1 | Study did not include any inclusion/exclusion criteria relating to the determination of CRPS and trials were substantially heterogenous. Some studies diagnosed CRPS according to criteria, not necessarily patient relevant (see below). Children and adolescents were not excluded, but the trials did not involve such patient groups. Two of the trials used the same data.
Two studies were quasi experimental studies. 3/6 of RCTs were blinded. Small drop out rates in all trials. High risk of bias due to no blinding or inadequate descriptions of blinding. |
| «Aïm F, Klouche S, Frison A, et al. Efficacy of vitamin C in preventing complex regional pain syndrome after wrist fracture: A systematic review and meta-analysis. Orthop Traumatol Surg Res 2017;103(3)»2 | In 2 trials, CRPS was determined by having four from five or six symptoms from which all may not be patient relevant (e.g. difference in skin colour relative to the other arm). All trials were double-blinded. The total number of participants in the meta-analysis was low. Only two trials reported the treatment method. One trial with high risk of bias due to high rate of lost to follow-up and inadequate description of blinding. Small drop-out rate in other two studies. |
Results
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: low Assess the risk of bias and delete irrelevant sources of bias: The quality of evidence is downgraded due to indirectness (outcome not patient-relevant) and inconsistency (One study suggesting no benefit, had also more direct outcome and smaller prevalence of CRPS in control group than other studies). The results were imprecise, but that did not warrant another downgrade. I=intervention; C=comparison; CI=confidence interval; NA=not applicable; OR=odds ratio; RR=risk ratio | |||||
| «Seth I, Bulloch G, Seth N, et al. Effect of Perioperative Vitamin C on the Incidence of Complex Regional Pain Syndrome: A Systematic Review and Meta-Analysis. J Foot Ankle Surg 2022;61(4):748-754 »1 | 6 RCTs and two quasi-experimental studies, 747/680 patients | 3 to 12 months | NA | NA | OR=0.33 (0.17-0.63) |
| «Aïm F, Klouche S, Frison A, et al. Efficacy of vitamin C in preventing complex regional pain syndrome after wrist fracture: A systematic review and meta-analysis. Orthop Traumatol Surg Res 2017;103(3)»2 | 3 RCTs, 504/297 patients | 12 months | 5.2% | 12.8% | RR=0.47 (0.18-1.26) |
References
- Seth I, Bulloch G, Seth N, et al. Effect of Perioperative Vitamin C on the Incidence of Complex Regional Pain Syndrome: A Systematic Review and Meta-Analysis. J Foot Ankle Surg 2022;61(4):748-754 «PMID: 34961681»PubMed
- Aïm F, Klouche S, Frison A, et al. Efficacy of vitamin C in preventing complex regional pain syndrome after wrist fracture: A systematic review and meta-analysis. Orthop Traumatol Surg Res 2017;103(3):465-470 «PMID: 28274883»PubMed