Amadio, Peter C. M.D.

Journal of Bone & Joint Surgery - American Volume:
Evidence-Based Orthopaedics
Author Information

Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota

Article Outline

Vitamin C has been the subject of thousands of reports since Linus Pauling first suggested that it had a therapeutic effect in reducing the severity of the common cold1 and, later, in the treatment of cancer and atherosclerosis. Subsequently, larger population-based studies have nearly uniformly discounted these effects as resulting from various forms of research bias, often in the nature of the study design2-4. This prospective, randomized, blinded study reports an impressive effect from a daily dose of 500 mg of vitamin C on the subsequent development of RSD in patients with wrist fractures that were treated in a cast. What are we to make of this?

One can argue that the definition of RSD used in this study has not been validated. The reliability of this case definition has not been tested. We are not told how long the findings had to be present, or to what extent. We are not told how, or if, the investigators knew whether the patients actually took the pills they were given. Nevertheless, if the randomization and blinding were true, and we have no reason to doubt that they were, all of these problems should have been equally distributed between the treatment and placebo groups, and would not explain the large differences reported.

I have no doubt that the investigators have reported their observations honestly and accurately; it is with the interpretation of those findings that I have concerns. Most problematic for me is the rather weak hypothesis linking RSD and vitamin C. We do not know the pathophysiology of RSD; indeed, we do not know if it is a distinct pathophysiological entity at all. The presumption that toxic oxygen radicals have a role in RSD is based on limited data. Similarly, the evidence that vitamin C has a therapeutic effect based on scavenging these radicals is both limited and controversial, as noted above. Thus, although this study makes a strong case for the prophylactic use of vitamin C in moderate doses for patients with wrist fractures treated in casts, and although such doses are not likely to be harmful in the short term, I am not ready to add vitamin C to my treatment regimen just yet. The clinical logic supporting the connection is, to my mind, weak, and no mere P value can overcome that hurdle. I will await further evidence, and I would not be surprised if, as has been the case with so many other proposed therapeutic uses of vitamin C, future articles come to different conclusions.

Peter C. Amadio, M.D.

Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota

1. Pauling L.: Vitamin C and common cold. JAMA, 1971.216: 332,
2. Ascherio A; Rimm EB; Hernan MA; and et al.: Relation of consumption of vitamin E, vitamin C, and carotenoids to risk for stroke among men in the United States. Ann Intern Med., 1999.130: 963-70,
3. Greenberg ER; Baron JA; Tosteson TD; and et al.: A clinical trial of antioxidant vitamins to prevent colorectal adenoma. Polyp Prevention Study Group. N Engl J Med, 1994.331: 141-7,
4. Hemila H, and Douglas RM: Vitamin C and acute respiratory infections. Int J Tuberc Lung Dis, 1999.3: 756-61,
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