Vitamin E: absorption, plasma transport and cell uptake

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Abstract
Large-scale clinical trials have failed to demonstrate a benefit for vitamin E supplementation in cardiovascular prevention. This contrasts with previous epidemiological studies indicating that individuals with high vitamin E status benefit from protection against chronic illnesses, including cardiovascular diseases. These conflicting results suggest that the metabolism of supplemental versus naturally delivered vitamin E and their potential roles, other than a potent antioxidant action, are not fully understood. The purpose of this review is to provide an update on current knowledge on the intestinal absorption of vitamin E, its plasma transport and its supply to cells. The review will also discuss the intravascular metabolism of intravenously delivered vitamin E. Although the luminal digestion of vitamin E is fairly well understood, several pathways regulating net vitamin E absorption remain to be elucidated. In several cell types, cholesterol and vitamin E share common mechanisms for cellular uptake (scavenger receptor B type I and LDL receptors) and efflux (ABCA1 transporters). The role of specific binding proteins in α-tocopherol intracellular trafficking is increasingly being understood, leading to new insights into the non-antioxidant functions of vitamin E. Substantial progress has been made in characterizing the plasma transport of vitamin E and its delivery to cells. Mechanisms regulating the balance between the cellular uptake and efflux of vitamin E are under investigation. Vitamin E is not only an antioxidant but may also modulate pathways of cell signalling and gene expression. The translation of this new knowledge into clinical studies will help define future indications for vitamin E supplementation.