Am J Clin Nutr 2002;76:703–16. Printed in USA. © 2002 American Society for Clinical Nutrition 703 The European perspective on vitamin E: current knowledge and future research1,2

Vitamin E is indispensible for reproduction in female rats. In humans, vitamin E deficiency primarily causes neurologic dys-functions, but the underlying molecular mechanisms are unclear. Because of its antioxidative properties, vitamin E is believed to help prevent diseases associated with oxidative stress, such as cardiovascular disease, cancer, chronic inflam-mation, and neurologic disorders. However, recent clinical tri-als undertaken to prove this hypothesis failed to verify a con-sistent benefit. Given these findings, a group of European scientists met to analyze the most recent knowledge of vitamin E function and metabolism. An overview of their discussions is presented in this article, which includes considerations of the mechanisms of absorption, distribution, and metabolism of dif-ferent forms of vitamin E, including the -tocopherol transfer protein and -tocopherol–associated proteins; the mechanism of tocopherol side-chain degradation and its putative interaction with drug metabolism; the usefulness of tocopherol metabolites as bio-markers; and the novel mechanisms of the antiatherosclerotic and anticarcinogenic properties of vitamin E, which involve modula-tion of cellular signaling, transcriptional regulation, and induction of apoptosis. Clinical trials were analyzed on the basis of the selection of subjects, the stage of disease, and the mode of intake, dosage, and chemical form of vitamin E. In addition, the scarce knowledge on the role of vitamin E in reproduction was summa-rized. In conclusion, the scientists agreed that the functions of vita-min E were underestimated if one considered only its antioxida-tive properties. Future research on this essential vitamin should focus on what makes it essential for humans, why the body appar-ently utilizes -tocopherol preferentially, and what functions other forms of vitamin E have. Am J Clin Nutr 2002;76:703–16. KEY WORDS Vitamin E, metabolism, binding proteins, novel functions, chemical form