Maret G. Traber, PhD

Ava Helen Pauling Professor,
Professor in the College of Health and Human Sciences,
Linus Pauling Institute
Oregon State University

image of Dr. Maret Traber
Abstract: Accurate estimates of the fractional vitamin E (α-T) absorption are needed in order to estimate the amount of dietary α-T to meet human α-T requirements. We hypothesized that the “dual isotope” technique would be an effective approach to determine α-T fractional absorption, disposition, metabolism and excretion. Following administration of differently labeled oral and IV doses, this technique estimates intestinal absorption from the plasma ratio, where the IV dose = 100% absorbed; after some equilibration of the two doses (estimated to be <24 h): Absorption = Area Under Curve (AUC) of the oral dose divided by AUC of the IV dose. Thus, α-T pharmacokinetics were studied in healthy adult women using a 30 mg dose of d6-α-T given in an intravenous (IV) oil/water emulsion and a similar d3-α-T amount in an oral dose. This clinical trial (NCT00862433) was carried out at the NIH Clinical Center; the NIH NIDDK/NIAMS Institutional Review Board for Protection of Human Subjects (IRB) approved the protocol (09-DK-0097); which is being carried out under the aegis of Dr. Mark Levine under an Investigational New Drug (IND) protocol (110033) issued by the FDA to him. The IV dose administration was preceded by 3 baseline samples 1 h apart, the oral d3-α-T dose placed as a drop of oil on the tongue, the breakfast shake (40% fat) was consumed, then the d6-α-T emulsion was given IV over approximately 7 minutes. The IV d6-α-T emulsion “disappeared” from the plasma within 10 minutes, similar to expected chylomicron clearance. The nadir in the IV d6-α-T concentrations occurred within 10 minutes post-infusion; then the d6-α-T increased over the next several h. Subsequently, the plasma d6-α-T concentrations decreased as a single exponential over 72 h. In contrast, the oral d3-α-T experienced a 2-3 h delay before appearing in the plasma and then the d3-α-T peaked in the circulation 6-12 h after dosing, then decreased exponentially. The d3- and d6-a-T (oral and IV dose, post nadir) curves increased and decreased in parallel consistent with expected equilibration of the two doses. Based on the ratio of the AUCs, the estimated absorption of the oral d3-α-T (30 mg) is 56% ± 12% (mean ± SD, n=9, 40% fat trial). These data, along with tissue α-T turnover, will be used to estimate how much dietary α-T is needed.