Vitamin E Pharmacokinetics and Oxidative Biomarkers in Normal and Obese Women
Maret G. Traber, Ph.D.
In Spring 2006 our lab got some exciting news. The NIH had requested that intramural investigators collaborate with scientists outside NIH and propose studies for the "Bench to Bedside" grant program. Mark A. Levine of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and I wrote a proposal to study vitamin E requirements in women. It was announced in June 2006 that our proposal was one of just 19 proposals selected for funding. The "Bench to Bedside" program is designed to speed translation of promising laboratory discoveries into new medical treatments. The Traber-Levine project will conduct research related to women’s health. Additional personnel at NIDDK who will work on this project include Sebastian J. Padayatty, He Sun, and Robert Wesley. Fred Stevens and Scott Leonard of LPI will also participate.
The rationale for our proposal is that although vitamin E (alpha-tocopherol) is essential for humans, there is no known "specific" alpha-tocopherol function, and thus it is difficult to set human dietary requirements. The current alpha-tocopherol requirements are based on studies in the 1950s and 60s in vitamin E-depleted menpsychiatric hospital patientsfed rancid fat for five years. These studies estimated the average daily requirement of vitamin E to be 12 mg of alpha-tocopherol. It is difficult for most Americans to obtain this much vitamin E in their usual diets. Vitamin E is present in nuts, seeds, and vegetable oils, such as sunflower oil, safflower oil, and olive oil. One cup of cooked spinach has about 6 mg; it would take more than two cups to get the current Recommended Dietary Allowance of 15 mg. Since less than 10% of Americans meet the vitamin E requirement, there is a question as to whether 12 mg of alpha-tocopherol per day is a valid estimate. Importantly, women were not studied, so there are no data available on women's requirements.
We plan to study healthy lean women, obese women, and diabetic obese women to estimate alpha-tocopherol pharmacokinetics and establish some additional relevant biomarkers. These data will be used to predict alpha-tocopherol requirements and to set new recommendations for vitamin E intakes. An accurate estimate of human dietary alpha-tocopherol requirements will ensure that adequate antioxidant protection can be obtained without excessive fat consumption. This concept is especially important for obese women who are advised to consume less fat and thus eat fewer vitamin E-containing foods.
Our hypothesis is that tissue stores of alpha-tocopherol are critical to its antioxidant function and that alpha-tocopherol delivery to tissues can be calculated from plasma alpha-tocopherol turnover. Alpha-tocopherol turnover will be characterized by the simultaneous oral and intravenous administration of two differently isotope-labeled alpha-tocopherols to the subjects. We will then calculate vitamin E absorption and disappearance rates in the different groups. Because we demonstrated earlier this year that vitamin C recycles vitamin E in cigarette smokers that have high oxidative stress, we will determine if vitamin C status is important for vitamin E status. Subjects will be studied twice: first, after they have consumed a "no" vitamin C diet for about four weeks until they have almost no measureable vitamin C in their plasma, and again after they have consumed vitamin C supplements for a month. These studies will directly test in the same subjects if vitamin C intakes affect vitamin E status in normal subjects. We also plan to conduct two pilot studies to determine the optimal fat intake for vitamin E absorption and the size of the vitamin E dose that does not alter vitamin E kinetics.
We are especially excited to be chosen for this special NIH project and hope to report our findings in two years!
Lasted updated November, 2006