Level 1: Likely reliable evidence

Two randomized trials by the same authors evaluated the efficacy of vitamin C supplementation for prevention of complex regional pain syndrome (CRPS) type I (formerly referred to as reflex sympathetic dystrophy) following wrist fracture. One trial included 416 mostly elderly women with 427 wrist fractures who were randomized to receive oral vitamin C 200, 500, or 1,500 mg vs. placebo daily for 50 days (J Bone Joint Surg Am. 2007;89:1424-1431). The rates of type I CRPS were 10.1% with placebo and 2.4% with vitamin C (all dosing groups combined) (P=.002, NNT 13 vs. placebo), 4.2% with vitamin C 200 mg (not significant vs. placebo), 1.8% with vitamin C 500 mg (NNT 12 vs. placebo), and 1.7% with vitamin C 1,500 mg (NNT 12 vs. placebo).

The other, earlier trial included 123 adults with 127 conservatively treated wrist fractures who were randomized to vitamin C 500 mg vs. placebo orally once daily for 50 days (Lancet. 1999;354:2025-2028). Eight patients were withdrawn after randomization. At one-year follow-up, the rates of CRPS were 7% with vitamin C 500 mg vs. 22% with placebo (NNT 7); this outcome was associated with borderline statistical significance.

While vitamin C supplementation is generally regarded as safe, it has been associated with adverse effects: osmotic diarrhea (total vitamin C intake >2,000 mg/day), kidney stone formation (>1,000 mg/day), decreased efficacy of chemotherapeutic agents, increased estrogen effects, and increased aluminum absorption (of significance with phosphate-binder use in patients with renal failure).