A feasibility study quantifying in vivo human alpha-tocopherol metabolism.
BACKGROUND
Quantitation of human vitamin E metabolism is incomplete, so we quantified RRR- and all-rac-alpha-tocopherol metabolism in an adult.


OBJECTIVE
The objective of the study was to quantify and interpret in vivo human vitamin E metabolism.


METHODS
A man was given an oral dose of 0.001821 micromol [5-14CH3]RRR-alpha-tocopheryl acetate (with 101.5 nCi 14C), and its fate in plasma, plasma lipoproteins, urine, and feces was measured over time. Data were analyzed and interpreted by using kinetic modeling. The protocol was repeated later with 0.001667 micromol [5-14CH3]all-rac-alpha-tocopheryl acetate (with 99.98 nCi 14C).


RESULTS
RRR-alpha-tocopheryl acetate and all-rac-alpha-tocopheryl acetate were absorbed equally well (fractional absorption: approximately 0.775). The main route of elimination was urine, and approximately 90% of the absorbed dose was alpha-2(2'-carboxyethyl)-6-hydroxychroman. Whereas 93.8% of RRR-alpha-tocopherol flow to liver kinetic pool B from plasma was returned to plasma, only 80% of the flow of all-rac-alpha-tocopherol returned to plasma; the difference (14%) was degraded and eliminated. Thus, for newly digested alpha-tocopherol, the all-rac form is preferentially degraded and eliminated over the RRR form. Respective residence times in liver kinetic pool A and plasma for RRR-alpha-tocopherol were 1.16 and 2.19 times as long as those for all-rac-alpha-tocopherol. Model-estimated distributions of plasma alpha-tocopherol, extrahepatic tissue alpha-tocopherol, and liver kinetic pool B for RRR-alpha-tocopherol were, respectively, 6.77, 2.71, and 3.91 times as great as those for all-rac-alpha-tocopherol. Of the lipoproteins, HDL had the lowest 14C enrichment. Liver had 2 kinetically distinct alpha-tocopherol pools.


CONCLUSIONS
Both isomers were well absorbed; all-rac-alpha-tocopherol was preferentially degraded and eliminated in urine, the major route. RRR-alpha-tocopherol had a longer residence time and larger distribution than did all-rac-alpha-tocopherol. Liver had 2 distinct alpha-tocopherol pools. The model is a hypothesis, its estimates are model-dependent, and it encourages further testing.
Clifford
Andrew J
AJ
Department of Nutrition, University of California, Davis, Davis, CA 5616-8669, USA. ajclifford@ucdavis.edu
de Moura
Fabiana F
FF
Ho
Charlene C
CC
Chuang
Jennifer C
JC
Follett
Jennifer
J
Fadel
James G
JG
Novotny
Janet A
JA
D000328:Adult; D001682:Biological Availability; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D005240:Feasibility Studies; D005243:Feces / Q000737:chemistry*; D006801:Humans; D007408:Intestinal Absorption; D007700:Kinetics; D008074:Lipoproteins / Q000097:blood / Q000737:chemistry*; D008099:Liver / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D013237:Stereoisomerism; D024505:Tocopherols; D016482:Urinalysis; D014810:Vitamin E / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D014815:Vitamins / Q000378:metabolism / Q000493:pharmacokinetics / Q000652:urine; D024502:alpha-Tocopherol / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine
D002250:Carbon Radioisotopes; D008074:Lipoproteins; D014815:Vitamins; D014810:Vitamin E; D024502:alpha-Tocopherol; D024505:Tocopherols