Do free radicals play causal role in atherosclerosis? Low density lipoprotein oxidation and vitamin E revisited.

Lipid peroxidation induced by free radicals has been implicated in the pathogenesis of various diseases. Numerous in vitro and animal studies show that oxidative modification of low density lipoprotein (LDL) is an important initial event of atherosclerosis. Vitamin E and other antioxidants inhibit low density lipoprotein oxidation efficiently in vitro, however, human clinical trials with vitamin E have not yielded positive results. The mixed results for vitamin E effect may be ascribed primarily to the two factors. Firstly low density lipoprotein oxidation proceeds by multiple pathways mediated not only by free radicals but also by other non-radical oxidants and vitamin E is effective only against free radical mediated oxidation. Secondly, in contrast to animal experiments, vitamin E is given at the latter stage where oxidation is no more important. Free radicals must play causal role in pathogenesis of atherosclerosis and vitamin E should be effective if given at right time to right subjects.