|FADEL, JAMES - University Of California|
|HOLSTEGE, DIRK - University Of California|
|FURR, HAROLD - University Of Wisconsin|
|CLIFFORD, ANDREW - University Of California|
Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/3/2012
Publication Date: 12/1/2012
Citation: Novotny Dura, J., Fadel, J.G., Holstege, D.M., Furr, H.C., Clifford, A.J. 2012. Kinetics, bioavailability, and metabolism of RRR-alpha-tocopherol in humans supports lower requirement for vitamin E. Journal of Nutrition. 142:2105-2111.
Interpretive Summary: Vitamin E is a nutrient essential to support life. However, the specific dietary requirement for vitamin E is uncertain. The current dietary requirement for vitamin E is based on sparse data related to how much vitamin E must be consumed to provide a blood level that will protect red blood cells from hydrogen peroxide damage in a laboratory test. However, this blood assay of vitamin E function is not necessarily tightly associated with actual vitamin E need. Using several cutting edge technologies related to specially tagging vitamin E, administering that tagged vitamin E to humans, measuring that tagged vitamin E with an extremely specialized instrument called an accelerator mass spectrometer, and analyzing the data with mathematics, we studied the body’s absorption and elimination of vitamin E. Twelve healthy adults consumed the tagged vitamin E, and serial blood, urine, and feces were collected for up to 70 days. We used a mathematical analysis called compartmental modeling to determine the absorption efficiency, total pool storage, blood and tissue half-lives, and elimination rates of vitamin E in the human body. The results of our study demonstrated that the target blood values for vitamin E can be maintained with a daily intake much lower than the current recommended daily allowance (RDA). This information is expected to be very useful for future dietary intake recommendations. These results will be used by scientists and health professionals.
Technical Abstract: Kinetic models enable nutrient needs and kinetic behaviors to be quantified and provide mechanistic insights into metabolism. Therefore, we modeled and quantified the kinetics, bioavailability and metabolism of RRR-alpha-tocopherol in 12 healthy adults. Six men and six women, aged 27 ± 6 y, each ingested 1.81 nmol of [5-(14)CH(3)]-(2R, 4'R, 8'R)-alpha-tocopherol; each dose had 3.70 kBq of carbon-14. Complete collections of urine and feces were made over the first 21 days since dosing. Serial blood samples were drawn over the first 70 days since dosing. All specimens were analyzed for RRR-alpha-tocopherol and its metabolite, carboxyethyl-hydroxychroman (CEHC). Specimens were also analyzed for carbon-14 using accelerator mass spectrometry. From this data, we modeled and quantified the kinetics of RRR-alpha-tocopherol as it occurs in vivo in humans. The model had 11 compartments, 3 delay compartments, and reservoirs for urine and feces. Bioavailability of RRR-alpha-tocopherol was 81 ± 1 %. The model estimated residence time and half-life of the slowest turning-over pool of alpha-tocopherol (adipose tissue) at 499 ± 702 d and 184 ± 84 d, respectively. The total body store of' RRR-alpha-tocopherol was 25,937 ± 6,218 micromol (11 ± 3 g), and we calculated the adipose tissue level of to be 657 microg/g. We found a daily intake of 9.2 micromol (4 mg) of RRR-alpha-tocopherol maintained plasma RRR-alpha-tocopherol levels at 23 micromol/L. These findings suggest that the dietary requirement for vitamin E may be less than the current Recommended Dietary Allowance, and these results will be important for future updates of intake recommendations.