Vitamin C for complex regional pain syndrome prophylaxis

Issue: BCMJ, vol. 61, No. 9, November 2019, Page 349 WorkSafeBC

Complex regional pain syndrome (CRPS), previously known as reflex sympathetic dystrophy (RSD) and causalgia, can be a debilitating complication of pain associated with limb trauma, including surgery. CRPS is associated with autonomic, sensory, and motor abnormalities, as well as physical changes to the skin and bone. Diagnosis is based on the Budapest Criteria (see box). CRPS can affect patients’ work, social activities, and psychological well-being. If started early, available treatments can be effective, but some patients suffer indefinitely.

With limited treatments and often poor outcomes, prevention of CRPS would be ideal. A 1999 randomized, double-blind study proposed vitamin C as possible prophylaxis for CRPS after distal radius fracture. Subsequent studies varied in supporting these findings or found no difference in outcomes. A 2013 systematic review and meta-analysis found that vitamin C 500 mg daily for 45 to 50 days posttrauma may help reduce the occurrence of CRPS; while a 2015 meta-analysis of only three larger studies found no difference in outcome. The latter meta-analysis noted that one study showing no difference used different diagnostic criteria than the two that found vitamin C prophylactic (all used pre-Budapest criteria). A 2017 systematic review and meta-analysis found that vitamin C (500 mg daily for 50 days) may halve the risk of CRPS within the first year after a distal radius fracture.

So that’s nice, but should we be giving vitamin C after distal radius fracture or foot and ankle trauma, the areas with the most research so far? The Royal College of Physicians in the UK updated its guidelines for diagnosis and management of CRPS in 2018. While the College did not include vitamin C in the main section, appendix 7, Post-fracture/operation patient information leaflet, states that “Vitamin C 500 mg daily for the first 6 weeks may help to reduce the risk of complications.” The American Academy of Orthopaedic Surgeons Clinical Practice Guidelines on Distal Radius Fractures recently downgraded the recommendation of adjuvant vitamin C to moderate, noting limitations in the available literature. And that probably says it best: the literature suggested that vitamin C may reduce the chance of developing CRPS but is not conclusive and further studies are needed. In the meantime, vitamin C (500 mg daily for 5 to 6 weeks) is extremely low risk and there is moderate evidence that it reduces the chance of developing a potentially debilitating complication.
—Derek Smith, MD, FRCSC
WorkSafeBC Special Advisor, Orthopaedic Surgery

Suggested reading

Aim 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;103:465-470.

Bharwani KD, Dirckx M, Huygen FJPM. Complex regional pain syndrome: Diagnosis and treatment. BJA Educ 2017;17:262-268.

Bussa M, Mascaro A, Cuffaro L, Rinaldi S. Adult complex regional pain syndrome type I: A narrative review. PM R 2017;9:707-719.

Evaniew N, McCarthy C, Kleinlugtenbelt YV, et al. Vitamin C to prevent complex regional pain syndrome in patients with distal radius fractures: A meta-analysis of randomized controlled trials. J Orthop Trauma 2015;29:e235-241.

Goebel A, Barker CH, Turner-Stokes L, et al. Complex regional pain syndrome in adults: UK guidelines for diagnosis, referral and management in primary and secondary care. London: RCP 2018.

Harden RN, Bruehl S, Perez RS, et al. Validation of proposed diagnostic criteria (the “Budapest Criteria”) for complex regional pain syndrome. Pain 2010;150:268-274.

Shibuya N, Humphers JM, Agarwal MJ, Jupiter DC. Efficacy and safety of high-dose vitamin C on complex regional pain syndrome in extremity trauma and surgery-systematic review and meta-analysis. J Foot Ankle Surg 2013;52:62-66.

Zollinger PE, Tuinebreijer WE, Breederveld RS, Kreis RW. Can vitamin C prevent complex regional pain syndrome in patients with wrist fractures? A randomized, controlled, multicenter dose-response study. J Bone Joint Surg Am 2007;89:1424-1431.

Zollinger PE, Tuinebreijer WE, Kreis RW, Breederveld RS. Effect of vitamin C on frequency of reflex sympathetic dystrophy in wrist fractures: A randomised trial. Lancet 1999;354(9195):2025-2028.


This article is the opinion of WorkSafeBC and has not been peer reviewed by the BCMJ Editorial Board.

Derek Smith, MD, FRCSC. Vitamin C for complex regional pain syndrome prophylaxis. BCMJ, Vol. 61, No. 9, November, 2019, Page(s) 349 - WorkSafeBC.

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