In human skin, highest alpha-tocopherol levels are found in facial sebum. We hypothesized that the bioavailability of vitamin E in human skin is, at least in part, dependent on sebaceous gland secretion. To test this, 24 volunteers were subjected to a randomized daily supplementation with either 400 mg RRR-alpha-tocopheryl acetate (RRR-alpha-toc) or 400 mg all-rac-alpha-tocopheryl acetate (all-rac-alpha-toc) for 14 days. Fasting blood samples, facial sebum samples, and lower-arm skin-surface lipids (SSL) were taken at time-points between 0-21 days. Samples were analyzed by HPLC for alpha-tocopherol and squalene concentrations. Increased serum alpha-tocopherol levels were detectable as early as 12 h after supplementation of RRR-alpha-toc or all-rac-alpha-toc and peaked on day 7. No significant changes were observed in lower-arm SSL. Remarkably, while unchanged until day 14, alpha-tocopherol sebum levels were increased on day 21 in both the RRR-alpha-toc and the all-rac-alpha-toc group by 87% and 92%, respectively. With respect to dietary supplementation of vitamin E and its bioavailability in human skin, these results suggest that (1) sebaceous gland secretion is a relevant delivery mechanism; (2) the bioavailabilities of RRR-alpha-toc and the all-rac-alpha-toc are similar; and (3) significant accumulation requires a daily supplementation period of at least 2-3 weeks.