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

Background: 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. Objective: 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. Design: 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. Results: 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- tod₃-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. Conclusion: 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. [ABSTRACT FROM AUTHOR]