VITAMIN-E DOSE-RESPONSE STUDIES IN HUMANS WITH USE OF DEUTERATED RRR-ALPHA-TOCOPHEROL

Background: Supplemental vitamin E does not raise plasma alpha-tocophe rol concentrations more than approximate to 3-fold. Objective: To eluc idate the mechanism for the limitation in plasma alpha-tocopherol, we undertook human supplementation trials using incrementally increased d oses of deuterated vitamin E. Design: Plasma was obtained from 6 healt hy, young adults (4 men and 2 women) during 3 sequential supplementati on trials with doses of 15, 75, and 150 mg RRR-alpha-tocopheryl acetat e labeled with deuterium (d(3)-RRR-alpha-tocopheryl acetate). A define d diet was provided on the day of deuterated vitamin E administration, but otherwise subjects ate ad libitum. Results: The areas under the c urves calculated from the plasma d(3)-RRR-alpha-tocopherol concentrati ons increased linearly with dose-a 10-fold increase in dose resulted i n a 10-fold increase in area under the curve. d(3)-RRR-alpha-Tocophero l absorption and incorporation into plasma did not decrease with incre asing dose. At 11 h, the 15-, 75-, and 150-mg doses resulted in 8 +/- 4%, 21 +/- 10%, and 37 +/- 20% labeling, respectively, of plasma vitam in E. Plasma total (labeled plus unlabeled) alpha-tocopherol concentra tions before supplementation were 12 +/- 3 mu mol/L and over the 96 h after the dose averaged 13.3 +/- 2.6, 15.4 +/- 3.0, and 16.7 +/- 4.9 m u mol/L for the 15-, 75-, and 150-mg doses, respectively. Conclusions: d(3)-RRR-alpha-Tocopherol was incorporated into the plasma in prefere nce to circulating plasma RRR-alpha-tocopherol. This could occur if th e newly absorbed d(3)-RRR-alpha-tocopherol was preferentially used to replenish circulating vitamin E.