Efficacy of vitamin C in preventing complex regional pain syndrome after wrist fracture: A systematic review and meta-analysis

Orthop Traumatol Surg Res. 2017 May;103(3):465-470. doi: 10.1016/j.otsr.2016.12.021. Epub 2017 Mar 4.


Background: Complex regional pain syndrome type I (CRPS-I), previously known as reflex sympathetic dystrophy, is common after conservatively or surgically treated wrist fractures. Several studies support the efficacy of vitamin C in preventing CRPS-I, although the data are somewhat conflicting. The primary objective of this systematic literature review and meta-analysis was to assess the efficacy of vitamin C therapy in preventing CRPS-I after a wrist fracture.

Methods: Randomised, placebo-controlled trials of vitamin C to prevent CRPS-I after wrist fractures were sought in the three main databases: PubMed (1980 to December 2015), CENTRAL (Central 2015, number 12), and Embase (1980 to December 2015). Two authors worked independently to select articles. Data from selected articles were collected independently.

Results: Three randomised placebo-controlled trials in a total of 875 patients were included. Treatment was non-operative in 758/890 (85.1%) fractures and operative in 132 (14.9%) fractures. Vitamin C supplementation was started on the day of the injury and continued for 50 days. In the group given 500mg of vitamin C daily, the risk ratio for CRPS-I was 0.54 (95%CI, 0.33-0.91; P=0.02). Thus, the risk of developing CRPS-I was significantly decreased by prophylactic treatment with 500mg of vitamin C per day. The heterogeneity rate was 65% (non-significant).

Conclusion: Daily supplementation with 500mg of vitamin C per day for 50 days decreases the 1-year risk of CRPS-I after wrist fracture.

Level of evidence: II, systematic review of level I and II studies.

Keywords: Complex regional pain syndrome type I; Meta-analysis; Prevention; Vitamin C; Wrist fracture.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antioxidants / therapeutic use*
  • Ascorbic Acid / therapeutic use*
  • Complex Regional Pain Syndromes / etiology*
  • Complex Regional Pain Syndromes / prevention & control*
  • Humans
  • Radius Fractures / complications*
  • Randomized Controlled Trials as Topic
  • Ulna Fractures / complications*
  • Wrist Injuries / complications


  • Antioxidants
  • Ascorbic Acid