Vitamin E and the Antioxidant Network: Protection of Human Low Density Lipoprotein from Oxidation

Abstract

The oxidation of human low density lipoprotein (LDL) is thought to initiate a series of pathological changes that eventually result in atherosclerosis. With diabetes atherogenesis may be accelerated by oxidative processes. Vitamin E is the major antioxidant in LDL, where it is important for protection from oxidation. When following the time course of LDL oxidation, an initial lag period is observed before oxidation commences, during which time antioxidants are consumed. The lag period is reported to be correlated with the LDL vitamin E content. Thus human subjects who consume vitamin E supplements exhibit a dose-dependent increase in the duration of the lag phase before oxidation of LDL is observed. Ascorbate and the thiol antioxidants reduced glutathione and dihydrolipoic acid (the dithiol thioctic acid) have been shown to regenerate vitamin E from its one electron oxidation product. The oxidized thiols can be reduced by enzymatic pathways utilizing reducing equivalents from NADH or NADPH. These enzymatic pathways, the thiol antioxidants, and the antioxidant vitamins E and C constitute a network of redox antioxidants. Supplementing isolated LDL preparations with these antioxidants increases lag time and protects LDL from oxidation. Consistent with epidemiological and prospective studies, these studies suggest that vitamin E supplementation is protective against the pathological changes that eventually result in atherosclerosis and cardiovascular disease.