Incorporation of deuterated RRR- or all-rac-α-tocopherol in plasma and tissues of α-tocopherol transfer protein–null mice123

• Published in: The American journal of clinical nutrition 2002-03, Vol.75 (3), p.555-560
• Main Authors: Leonard, Scott W, Terasawa, Yuko, Farese Jr, Robert V, Traber, Maret G
• Format: Article
• Language: English
• Subjects: brain; deuterium-labeled α-tocopherol; liver; mass spectrometry; Vitamin E; vitamin E requirement; α-TTP knockout mice
• ISSN: 0002-9165
• DOI: 10.1093/ajcn/75.3.555

Most vitamin E supplements contain synthetic all-rac-α-tocopherol [2,5,7,8-tetramethyl-2RS-(4′RS,8′RS,12-trimethyltridecyl)-6-chromanol] with 8 stereoisomers; only 1 is identical to the natural stereoisomer, RRR-α-tocopherol [2,5,7,8-tetramethyl-2R-(4′R,8′R,12-trimethyltridecyl)-6-chromanol]. In humans, 2R-α-tocopherol stereoisomers are preferentially maintained in the plasma, a function that has been attributed to hepatic α-tocopherol transfer protein (α-TTP), but this hypothesis has not been tested. We sought to determine the functions of α-TTP by comparing mice that express α-TTP with mice that are genetically unable to express α-TTP. Adult α-TTP null (Ttpa−/−; n = 5), heterozygous (Ttpa+/−; n = 7), and wild-type (Ttpa+/+; n = 3) mice consumed equimolar RRR-α-[5,7-(C2H3)2]-(d6)- and all-rac-α-[5-(C2H3)]-(d3)-tocopheryl acetates (30 mg/kg diet each) for 3 mo. Subsequently, we measured labeled and unlabeled α-tocopherols in plasma and 17 tissues. In all mice, plasma and tissue d6- + d3-α-tocopherols represented ≈80–90% of total α-tocopherol. In the Ttpa−/− mice, low total α-tocopherol concentrations were found in plasma (5.4%) and most other tissues (2–20%), but liver concentrations were 39% of those of Ttpa+/+ mice. Peripheral tissue ratios of d6- to d3-α-tocopherol were 1.1 ± 0.1 and 1.8 ± 0.2 in Ttpa−/− and Ttpa+/+ mice, respectively (P < 0.0001), showing that α-TTP preferentially selects 2R-α-tocopherols for secretion into plasma. This 2:1 ratio does not support the currently defined international unit of 1.36:1 RRR-α-tocopherol to all-rac-α-tocopherol. Deletion of the α-TTP gene in mice results in an accumulation of dietary α-tocopherol in the liver and depletion of peripheral tissue α-tocopherol.