Vitamin E dose-response studies in humans with use of deuterated RRR-alpha-tocopherol

Background: Supplemental vitamin E does not raise plasma α-tocopherol concentrations more than 3-fold. Objective: To elucidate the mechanism for the limitation in plasma α-tocopherol, we undertook human supplementation trials using incrementally increased doses of deuterated vitamin E. Design: Plasma was obtained from 6 healthy, young adults (4 men and 2 women) during 3 sequential supplementation trials with doses of 15, 75, and 150 mg RRR-α-tocopheryl acetate labeled with deuterium (d 3 -RRR-α-tocopheryl acetate). A defined diet was provided on the day of deuterated vitamin E administration, but otherwise subjects ate ad libitum. Results: The areas under the curves calculated from the plasma d 3 -RRR-α-tocopherol concentrations increased linearly with dose-a 10-fold increase in dose resulted in a 10-fold increase in area under the curve. d 3 -RRR-α-Tocopherol absorption and incorporation into plasma did not decrease with increasing dose. At 11 h, the 15-, 75-, and 150-mg doses resulted in 8 ± 4%, 21 ± 10%, and 37 ± 20% labeling, respectively, of plasma vitamin E. Plasma total (labeled plus unlabeled) α-tocopherol concentrations before supplementation were 12 ± 3 μmol/L and over the 96 h after the dose averaged 13.3 ± 2.6, 15.4 ± 3.0, and 16.7 ± 4.9 μmol/L for the 15-, 75-, and 150-mg doses, respectively. Conclusions: d 3 -RRR-α-Tocopherol was incorporated into the plasma in preference to circulating plasma RRR-α-tocopherol, This could occur if the newly absorbed d 3 -RRR-α-tocopherol was preferentially used to replenish circulating vitamin E.