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Free Radic Biol Med. 2017 Jan;102:16-36. doi: 10.1016/j.freeradbiomed.2016.09.017. Epub 2016 Nov 2.

Vitamin E: Emerging aspects and new directions.

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Department of Pharmaceutical Sciences, University of Perugia, Laboratory of Clinical Biochemistry and Nutrition, Via del Giochetto, 06126 Perugia, Italy. Electronic address:
USDA-HNRCA at Tufts University, 711 Washington St., Boston, MA 02111, United States. Electronic address:
Department of Nutritional, Food and Consumer Sciences, Fulda University of Applied Sciences, Leipziger Straße 123, 36037 Fulda, Germany. Electronic address:
Allergy/Immunology Division, Northwestern University, 240 E Huron, Chicago, IL 60611, United States. Electronic address:
DSM Nutritional Products, Wurmisweg 576, 4303 Kaiseraugst, Switzerland. Electronic address:
Institute of Biological Chemistry and Nutrition, University of Hohenheim, Garbenstr. 28, 70599 Stuttgart, Germany. Electronic address:
Department of Chemistry, Biology and Biotechnology, University of Perugia, Italy. Electronic address:
Institute of Nutrition, Friedrich Schiller University Jena, Dornburger Str. 25, 07743 Jena, Germany; Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, Germany. Electronic address:
Department of Biochemistry, Faculty of Medicine, Genetic and Metabolic Diseases Research Center (GEMHAM), Marmara University, 34854 Maltepe, Istanbul, Turkey. Electronic address:


The discovery of vitamin E will have its 100th anniversary in 2022, but we still have more questions than answers regarding the biological functions and the essentiality of vitamin E for human health. Discovered as a factor essential for rat fertility and soon after characterized for its properties of fat-soluble antioxidant, vitamin E was identified to have signaling and gene regulation effects in the 1980s. In the same years the cytochrome P-450 dependent metabolism of vitamin E was characterized and a first series of studies on short-chain carboxyethyl metabolites in the 1990s paved the way to the hypothesis of a biological role for this metabolism alternative to vitamin E catabolism. In the last decade other physiological metabolites of vitamin E have been identified, such as α-tocopheryl phosphate and the long-chain metabolites formed by the ω-hydroxylase activity of cytochrome P-450. Recent findings are consistent with gene regulation and homeostatic roles of these metabolites in different experimental models, such as inflammatory, neuronal and hepatic cells, and in vivo in animal models of acute inflammation. Molecular mechanisms underlying these responses are under investigation in several laboratories and side-glances to research on other fat soluble vitamins may help to move faster in this direction. Other emerging aspects presented in this review paper include novel insights on the mechanisms of reduction of the cardiovascular risk, immunomodulation and antiallergic effects, neuroprotection properties in models of glutamate excitotoxicity and spino-cerebellar damage, hepatoprotection and prevention of liver toxicity by different causes and even therapeutic applications in non-alcoholic steatohepatitis. We here discuss these topics with the aim of stimulating the interest of the scientific community and further research activities that may help to celebrate this anniversary of vitamin E with an in-depth knowledge of its action as vitamin.


Antioxidants; Cytochrome P-450; Long-chain metabolites, Tocopheryl phosphate; NASH; Nutrition; Tocopherols; Tocotrienols; Vitamin E

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