Is methyl-branching in α-tocopherol's “tail” important for its in vivo activity? Rat curative myopathy bioassay measurements of the vitamin E activity of three 2RS-n-alkyl-2,5,7,8-tetramethyl-6-hydroxychromans

Abstract The vitamin E activity of the acetates of three 2RS-n-alkyl-2,5,7,8-tetramethyl-6-hydroxychroman analogs of α-tocopherol have been measured and compared directly with all - rac -α-tocopheryl acetate, or indirectly via 2 R ,4′ R ,8′ R - α -tocopheryl acetate, using the rat curative myopathy, plasma pyruvate kinase assay. The analogs with alkyl chain lengths of 11 and 13 carbons have activities which not only do not differ significantly ( p > 0.05) from each other but also do not differ from that of all - rac -α-tocopheryl acetate. This finding indicates that branching in the phytyl tail at the 4′, 8′, and 12′ positions has little if any influence upon vitamin E activity. Thus physical interactions involving the methyl branches of the phytyl tail and the polyunsaturated moieties of membrane phospholipids are unimportant in vivo, insofar as this bioassay is concernced. However, the length of the hydrocarbon tail is important. This is indicated by the result obtained which the acetate of the analog with an alkyl chain length of 15 carbon atoms which had only 15% of the activity of 2 R ,4′ R ,8′ R - α -tocopheryl acetate, i.e., 22% of the activity of all - rac -α-tocopheryl acetate since this form is 1.47 times less active than 2 R ,4′ R ,8′ Rα -tocopheryl acetate in the curative myopathy bioassay (Weiser, Vecchi, & Schlachter, Internat. J. Vit. Nutr. Res. 55: 149–158, 1985).