Changing Concepts of the Antisterility Vitamin (Vitamin E) *

At the time of its discovery two decades ago, vitamin E would have been defined as the fifth member of the then small family of vitamins. It was known to be widely distributed in green plants, in the germ of cereal grains, and, to a lesser extent, in animal tissues. It was known to be essential for normal reproduction in the laboratory rat. Although its ability to prevent fetal resorption in the female rat still constitutes the standard measure of its biological activity, a wide variety of seemingly unrelated changes have since been observed in the rat and in other laboratory animals as consequences of deprivation of the vitamin. Before discussing these lesions it may be appropriate to summarize briefly what we know concerning the nature and distribution of the vitamin. In 1936 Evans and his associates"3 isolated from wheat-germ oil an alcohol having marked vitamin-E activity, for which the term alpha-tocopherol (tokos-offspring; pheros-to bear) was proposed. Within two years its chemical structure was determined and its laboratory synthesis accomplished. It is now recognized that three tocopherols (alpha, beta, and gamma), all of which are viscous oils, are the only substances in the plant world possessing vitamin-E activity. The isomeric forms, alpha and gamma, are lower homologues of alpha tocopherol. Biological assays of the natural, free forms of these tocopherols, in progress in my laboratory, indicate that alpha tocopherol is approximately twice as active as is beta tocopherol and four times as active as is the gamma form. Some 40 other compounds, produced synthetically, have been reported to show biological activity characteristic of the vitamin. None of these has proved as active as alpha tocopherol, the prototype of vitamin E. It is of interest to note that these tocopherols, while themselves susceptible to oxidation, also possess antioxygenic activity which is inversely proportional to their biological activity. The chemical nature of vitamin E and related compounds is extensively discussed in a recent review by Smith.29