Vitamin E modulation of cardiovascular disease.

Endothelium in the vascular system is an important modulator of vasomotor tone and coagulation, and it plays a crucial role in the inhibition of adhesion and activation of platelets and leukocytes. Evidence indicates that dietary antioxidants may modulate these endothelium-dependent vascular functions through several mechanisms and may contribute to the prevention of vascular diseases such as atherosclerosis. Several cell cultures as well as animal and human clinical and observational studies have tested the efficacy of vitamin E on vascular function and the prevention of atherosclerosis. Our cell culture studies have indicated that vitamin E (alpha-tocopherol) inhibits the activation of endothelial cells stimulated by high levels of low-density lipoprotein cholesterol and pro-inflammatory cytokines. This inhibition is associated with the suppression of chemokines, the expression of cell surface adhesion molecules, and the adhesion of leukocytes to endothelial cells, all of which contribute to the development of lesions in the arterial wall. The molecular mechanisms by which alpha-tocopherol and other tocopherols modulate endothelial cells and smooth muscle functions have been delineated. We, and others, have also demonstrated a positive effect of dietary vitamin E on endothelium and vascular function in animal models of atherosclerosis. Several human clinical trials have also shown an improvement in the surrogate markers of atherosclerosis and vascular function by vitamin E supplementation. However, these findings have been contradicted by several vitamin E supplementation trials for the prevention of secondary cardiovascular events showing null effect. Intervention at a relatively late stage of disease and the single use of vitamin E rather than in combination with other antioxidants might have contributed to these contradictory findings. Evidence from cell cultures, as well as animal and human clinical and observational studies, strongly supports the contribution of dietary vitamin E to the maintenance of vascular function and health, in particular when it is used in combination with other dietary antioxidants, which are found in fruits, vegetables, and nuts.