Elsevier

The Lancet

Volume 346, Issue 8966, 1 July 1995, Pages 36-38
The Lancet

Clinical trials of antioxidants in atherosclerosis: are we doing the right thing?

https://doi.org/10.1016/S0140-6736(95)92657-7Get rights and content

Abstract

The hypothesis that oxidative modification of low density lipoprotein contributes to the progression of atherosclerosis is supported by an impressive body of in-vitro findings and by persuasive results in animal models of atherosclerosis. The hypothesis was originally proposed specifically to account for foam cell formation but oxidation of LDL has now been shown to confer on it a long list of new biological properties any one of which could in principle enhance its atherogenicity.1,2 The relative importance of these altered biological properties in vivo remains uncertain. Whatever the precise mechanisms, we know that antioxidants can slow the atherogenic process in several experimental models, including LDL-receptor-deficient rabbits, cholesterol-fed rabbits, and cholesterol-fed non-human primates. Of 18 published studies, 13 have given strongly positive results, the rate of progression of lesions being reduced by 50-80%; 2 have yielded marginally positive results; and 3 have been negative (see ref 3 for references). Furthermore, the fact that four different antioxidant compounds have been used—probucol, butylated hydroxytoluene, N,N'-diphenyl-phenylenediamine, and vitamin E—supports the conclusion that they are working via the property they all share, namely, their antioxidant potential.

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