Vitamin E: murine studies versus clinical trials.

Vitamin E is the most effective lipid-soluble antioxidant present in mammalian cells. The hypothesis that links vitamin E to atherogenesis postulates that oxidative modifications of unsaturated fatty acids in the low-density lipoprotein particles play a crucial role in the pathogenesis of this chronic disease. Therefore, vitamin E supplementation should reduce the extent of oxidation and, thus, be protective against atherosclerosis. This hypothesis is strongly supported by studies in murine models of atherosclerosis. In contrast, clinical trials using this vitamin have been giving a more confused picture than expected, with results ranging from a significant protective action to the absence of any effect. However, these findings do not reduce the validity of the "oxidative hypothesis" and of the large body of experimental evidence accumulated so far in its favor. Several differences between animal studies and clinical trials, and among clinical trials themselves are taken into account in order to explain the conflicting findings. Finally, insights into what might be the most appropriate nature of future trials in humans are given.