Vitamin E: function and metabolism

Although vitamin E has been known as an essential nutrient for reproduction since 1922, we are far from understanding the mechanisms of its physiological functions. Vitamin E is the term for a group of tocopherols and tocotrienols, of which α-tocopherol has the highest biological activity. Due to the potent antioxidant properties of tocopherols, the impact of α-tocopherol in the prevention of chronic diseases believed to be associated with oxidative stress has often been studied, and beneficial effects have been demonstrated. Recent observations that the α-tocopherol transfer protein in the liver specifically sorts out RRR-α-tocopherol from all incoming tocopherols for incorporation into plasma lipoproteins, and that α-tocopherol has signaling functions in vascular smooth muscle cells that cannot be exerted by other forms of tocopherol with similar antioxidative properties, have raised interest in the roles of vitamin E beyond its antioxidative function. Also, γ-tocopherol might have functions apart from being an antioxidant. It is a nucleophile able to trap electrophilic mutagens in lipophilic compartments and generates a metabolite that facilitates natriuresis. The metabolism of vitamin E is equally unclear. Excess α-tocopherol is converted into α-CEHC and excreted in the urine. Other tocopherols, like γ- and δ-tocopherol, are almost quantitatively degraded and excreted in the urine as the corresponding CEHCs. All rac α-tocopherol compared to RRR-α-tocopherol is preferentially degraded to α-CEHC. Thus, there must be a specific, molecular role of RRR-α-tocopherol that is regulated by a system that sorts, distributes, and degrades the different forms of vitamin E, but has not yet been identified. In this article we try to summarize current knowledge on the function of vitamin E, with emphasis on its antioxidant vs. other properties, the preference of the organism for RRR-α-tocopherol, and its metabolism to CEHCs.—Brigelius-Flohé, R., Traber, M. G. Vitamin E: function and metabolism. FASEB J. 13, 1145–1155 (1999)