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

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Abstract
Supplemental vitamin E does not raise plasma alpha-tocopherol concentrations more than approximately 3-fold. To elucidate the mechanism for the limitation in plasma alpha-tocopherol, we undertook human supplementation trials using incrementally increased doses of deuterated vitamin E. 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-alpha-tocopheryl acetate labeled with deuterium (d3-RRR-alpha-tocopheryl acetate). A defined diet was provided on the day of deuterated vitamin E administration, but otherwise subjects ate ad libitum. The areas under the curves calculated from the plasma d3-RRR-alpha-tocopherol concentrations increased linearly with dose--a 10-fold increase in dose resulted in a 10-fold increase in area under the curve. d3-RRR-alpha-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) alpha-tocopherol concentrations before supplementation were 12+/-3 micromol/L and over the 96 h after the dose averaged 13.3+/-2.6, 15.4+/-3.0, and 16.7+/-4.9 micromol/L for the 15-, 75-, and 150-mg doses, respectively. d3-RRR-alpha-Tocopherol was incorporated into the plasma in preference to circulating plasma RRR-alpha-tocopherol. This could occur if the newly absorbed d3-RRR-alpha-tocopherol was preferentially used to replenish circulating vitamin E.