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A feasibility study quantifying in vivo human -tocopherol metabolism^1,2,3

¹ From the Departments of Nutrition (AJC, FFM, CCH, JCC, and JF) and Animal Science (JGF), University of California, Davis, Davis, CA, and the Diet and Human Performance Laboratory, US Department of Agriculture, ARS, BHNRC, Beltsville, MD (JAN)

Background: Quantitation of human vitamin E metabolism is incomplete, so we quantified RRR- and all-rac--tocopherol metabolism in an adult.

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

Design: A man was given an oral dose of 0.001821 µmol [5-¹⁴CH₃]RRR--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 µmol [5-¹⁴CH₃]all-rac--tocopheryl acetate (with 99.98 nCi ¹⁴C).

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

Conclusions: Both isomers were well absorbed; all-rac--tocopherol was preferentially degraded and eliminated in urine, the major route. RRR--tocopherol had a longer residence time and larger distribution than did all-rac--tocopherol. Liver had 2 distinct -tocopherol pools. The model is a hypothesis, its estimates are model-dependent, and it encourages further testing.

Key Words: -Tocopherol • isomer • human • metabolism • radiocarbon • accelerator mass spectrometry