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