Is the emperor wearing clothes? Clinical trials of vitamin E and the LDL oxidation hypothesis

A wealth of evidence indicates that oxidized low density lipoprotein (LDL) may be of central importance in animal models of atherogenesis. In recent c linical trials, however, dietary vitamin E supplements have not consistentl y prevented cardiac events in humans with established coronary artery disea se. Such mixed results have led many to question the role of LDL oxidation in human atherosclerosis, although this interpretation assumes that the dos es of vitamin E used in the studies inhibited lipid oxidation in vivo. In f act, there is remarkably little evidence indicating that those particular r egimens effectively inhibit lipid peroxidation in healthy humans. Moreover, evidence of increased oxidative stress was not a criterion for inclusion i n the trials; therefore, vitamin E may have benefited only a subset of the participants. These uncertainties raise doubts about the ability of vitamin E to augment antioxidant defense mechanisms in vivo and leave many questio ns about LDL oxidation and atherosclerosis unanswered.