Is there a potential therapeutic role for vitamin E or other antioxidants in atherosclerosis?
In-vitro studies and animal model studies provide an ever-growing body of evidence, direct and indirect, that oxidation of low-density lipoprotein and/or related oxidative mechanisms play a role in atherogenesis. However, two recent, very large, carefully conducted clinical intervention trials using adequate doses of vitamin E demonstrated no effect on a composite end-point of non-fatal infarction, stroke or death from cardiovascular causes. Why the unexpected negative results? Possibly because the animal intervention evidence on which these trials were based deals primarily with very early lesions (fatty streaks). That evidence does not necessarily provide a basis for predicting what antioxidant intervention will do in patients with advanced lesions, particularly when the end-points used relate to unstable plaques and fatal thrombosis, events for which we have no adequate animal models. Nor does it necessarily follow that the same antioxidants used successfully in animals will be effective in humans. The strength of the evidence for the oxidative modification hypothesis is such that negative clinical trials with one particular antioxidant, in patients with very advanced coronary heart disease and lasting only 3-5 years, should not be taken as refutation of the hypothesis. Perhaps different kinds of human trials are needed, trials in which the development of new lesions is measured, in order to test whether antioxidants can decrease the rate of initiation and early progression of atherosclerosis as they do in animals. The answer to the title query is 'Probably, but it is too soon to say'.
Steinberg
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University of California, San Diego, La Jolla, California 92093-0682, USA. dsteinberg@ucsd.edu
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001161:Arteriosclerosis / Q000628:therapy*; D002318:Cardiovascular Diseases / Q000188:drug therapy; D002986:Clinical Trials as Topic; D003327:Coronary Disease / Q000188:drug therapy; D006801:Humans; D008084:Lipoxygenase / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000188:drug therapy; D013045:Species Specificity; D020521:Stroke / Q000188:drug therapy; D013927:Thrombosis / Q000188:drug therapy; D014810:Vitamin E / Q000493:pharmacokinetics* / Q000627:therapeutic use*
D000975:Antioxidants; D014810:Vitamin E; D008084:Lipoxygenase