Vitamin E Pharmacokinetics and Biomarkers in Normal and Obese Women

Vitamin E (alpha-tocopherol) is essential for humans but determining human dietary requirements has proved difficult. The recommended dietary allowance (RDA) for vitamin E is not met by 96% of American women, without apparent harm. Because vitamin E is an antioxidant, optimum consumption of vitamin E may improve the health of obese women who experience high levels of inflammation and oxidative stress. We hypothesize that vitamin E functions as an antioxidant is related to its tissue stores, and that delivery to tissue stores can be calculated from plasma vitamin E turnover kinetics from slow release pools. We propose turnover kinetics as a new means to estimate vitamin E recommended dietary allowance. We will study vitamin E pharmacokinetics using dual stable-isotope labeled (deuterium) alpha-tocopherols administered orally and intravenously to healthy nonobese, overweight and overweight non-insulin requiring diabetic women. Blood samples will be collected at intervals and vitamin E measured by mass spectrometry. Because ascorbic acid (vitamin C) concentrations may alter alpha-tocopherol pharmacokinetics, subjects will be studied first at low and then high steady state plasma vitamin C concentrations. Before this main study, two preliminary trials will be performed. In preliminary trial 1, fat content for optimal absorption will be assessed because fat-content of a meal may alter vitamin E absorption. The fat content in preliminary trial 1 will be 0 - 40% of calories in the breakfast meal during which vitamin E will be administered. In preliminary trial 2, optimal fat content from preliminary trial 1 will be used, and the vitamin E dose will be varied. Vitamin E dose amount could non-specifically alter vitamin E kinetics. We will therefore determine the largest dose (2-30 mg) that does not non-specifically increase vitamin E turnover, with fat held constant. Additionally, we will measure vitamin E pharmacokinetics as a function of lipid peroxidation biomarkers to provide direct data that can be used to predict vitamin E requirements for women, and to set new recommendations for vitamin E intakes. We will explore new alpha-tocopherol functions, specifically whether gene transcription in human subjects is regulated by vitamin E status in relation to vitamin C status. Because vitamin E turnover may be affected by vitamin C concentrations, we will use a vitamin C depletion-repletion study design to investigate the relationship between vitamin C status and vitamin E turnover.