Clinical Health Updates

Vitamin C prevents RSD in patients with wrist fracture

Clinical Question:
Does vitamin C prevent complex regional pain syndromes (reflex sympathetic dystrophy) in patients with wrist fractures?

Bottom Line:
In patients with wrist fractures, we only need to treat 13 patients with vitamin C to prevent one case of reflex sympathetic dystrophy. Vitamin C reduces the prevalence of complex regional pain syndrome after wrist fractures. A daily dose of 500 mg for fifty days is recommended.

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.

Study Design:
Randomized controlled trial (double-blinded)


Four hundred sixteen adult patients (18 years or older) with a unilateral or bilateral wrist fracture (total 427 fractures) seen in the emergency department were randomly assigned to receive 50 days of placebo or vitamin C (daily doses of 200 mg, 500 mg or 1500 mg), regardless of whether the fractures were treated surgically or with immobilization. The main outcome of interest was whether the patient, by 12 months after the fracture, developed type 1 complex regional pain syndromes (reflex sympathetic dystrophy [RSD]). The diagnosis was made by the treating physician, who was masked to treatment and who used specific criteria, not by anyone involved in the study. The criteria for RSD was met when 4 of the following 5 symptoms were present or increased after activity: (1) unexplained diffuse pain not expected at the stage of fracture treatment; (2) a difference in skin color compared with the other hand and wrist; (3) diffuse edema; (4) a difference in skin temperature compared with the other hand and wrist; and (5) limited active range of motion of the wrist and fingers. The researchers had a remarkable 100% follow-up. At the end of the study, 10.1% of patients taking placebo developed RSD compared with 2.4% of those taking vitamin C (number needed to treat [NNT] = 13; 95% CI, 7 – 39). The rates of RSD by vitamin C dose was 4.2%, 1.8%, and 1.7%, respectively. So, it looks like 500 mg is the optimum daily dose. In a different study (Lancet 1999;354:2025-8), these same researchers also demonstrated vitamin C to be effective in preventing RSD after wrist fracture (NNT = 7).