ROLE OF DIETARY SELENIUM ON GENE EXPRESSION, CELL CYCLE AND MOLECULAR MECHANISMS IN CANCER RISK
Location: Grand Forks Human Nutrition Research Center
Title: A feasibiity study to quantify in vivo human alpha-tocopherol metabolism
| Clifford, Andrew - UNIV OF CALIFORNIA DAVIS |
| DE Moura, Fabiana - UNIV OF CALIFORNIA DAVIS |
| Ho, Charlene - UNIV OF CALIFORNIA DAVIS |
| Chuang, Jennifer - UNIV OF CALIFORNIA DAVIS |
| Follett, Jennifer |
| Fadel, James - UNIV OF CALIFORNIA DAVIS |
Submitted to: American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 7, 2006
Publication Date: December 15, 2006
Citation: Clifford, A.J., De Moura, F.F., Ho, C.C., Chuang, J.C., Follett, J.R., Fadel, J.G., Novotny Dura, J. 2006. A feasibiity study to quantify in vivo human alpha-tocopherol metabolism. American Journal of Clinical Nutrition. 84(6):1430-1441.
Interpretive Summary: The term vitamin E includes eight related molecules with differing structures and differing utility to the body. The form called alpha-tocopherol has the highest vitamin E activity. Naturally occurring alpha-tocopherol consists of a single form, while synthetic alpha-tocopherol (as found in supplements) consists of 8 different forms. The body tissues can distinguish among the different forms of vitamin E, and therefore different forms are metabolized at different rates. To determine the differences in rates of metabolism of natural alpha-tocopherol (from food) compared to synthetic alpha-tocopherol (from supplements), a study was conducted in which a healthy male consumed both forms tagged with a chemical tag called carbon-14. The carbon-14 tag allowed the vitamin E to be tracked in the body for a long period after the dose was ingested, and mathematical techniques were used to interpret the appearance of the tagged vitamin E in the blood, urine, and feces. The study showed that the vitamin E forms were absorbed equally well. Urine was the major route of elimination for both forms. The liver returned more of the natural form back to blood compared to the supplement form. The supplement form was degraded more quickly than the natural form. The natural form stayed in the body about 2 times longer than the supplement form. These results are useful for scientists conducting research on vitamin E metabolism.
Quantitation of human vitamin E metabolism is incomplete, therefore we conducted study to quantify RRR- and all-rac-alpha-tocopherol (TAc) metabolism in humans. A healthy male was administered an oral dose of 14C-labeled RRR-alpha-TAc (0.001821 micromol, 101.5 nCi 14C), and its appearance was measured in his plasma, urine, and feces over time after dosing. The protocol was repeated 3 months later with 14C-labeled all-rac-alpha-TAc (0.001667 micromol, 99.98 nCi 14C). 14C in biological samples was measured with Accelerator Mass Spectrometry. The data was analyzed and interpreted using a kinetic model. It was determined that the two forms of TAc were absorbed equally well. Urine was the major route of elimination (accounting for 90% of the absorbed dose). While 94% of RRR-alpha-TOC turnover in liver was directed to plasma, only 80% of liver all-rac-alpha-TOC turnover was directed to plasma, with the difference (14%) being degraded and eliminated. Residence times in liver and plasma were 1.16 and 2.19 times longer for the RRR form compared to the all-rac form. Conclusion: This kinetic analysis has revealed specific pathways that differ for metabolism of RRR vs. all-rac alpha tocopherol.