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Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions

-Tocotrienol and -Tocopherol Are Primarily Metabolized to Conjugated 2-(β-carboxyethyl)-6-Hydroxy-2,7,8-Trimethylchroman and Sulfated Long-Chain Carboxychromanols in Rats^1–3,

Department of Foods and Nutrition, Interdepartmental Nutrition Program, Purdue University, West Lafayette, IN 47907

The metabolism of -tocotrienol (-TE) and -tocopherol (-T) was investigated in human A549 cells and in rats. Similar to -T, A549 cells metabolized -TE to sulfated 9'-, 11'-, and 13'-carboxychromanol and their unconjugated counterparts. After 72-h incubation with the cells, 90% of long-chain carboxychromanols in the culture media from -TE, but <45% from -T, were in the sulfated form. The formation of these metabolites was further investigated in rats gavaged by -TE at 10 or 50 mg/kg, -T at 10 mg/kg, or tocopherol-stripped corn oil in controls. Six hours after a single dosing, the supplemented rats had increased plasma concentrations of 13'-carboxychromanol and sulfated 9'-, 11'-, 13'-carboxychromanol, whereas none of these metabolites were detectable in the controls. Sulfated 11'-carboxychromanol was the most abundant long-chain metabolite in -TE–supplemented rats. Sulfatase/glucuronidase hydrolysis revealed for the first time that >88% 2-(β-carboxyethyl)-6-hydroxychroman (-CEHC), the terminal β-oxidation metabolite, was in the conjugated form in the plasma. In all groups, conjugated -CEHC accounted for >75% of total metabolites, whereas free CEHC was a minor metabolite. At 10 mg/kg, the plasma concentrations of total metabolites from -TE–supplemented rats were higher (P < 0.05) than those from -T–fed rats. These results demonstrate that in rats, conjugation such as sulfation occurs parallel to β-oxidation in the liver and is quantitatively important to vitamin E metabolism. Conjugated long-chain carboxychromanols may be novel excreted metabolites during supplementation. Our data also provide in vivo evidence that -TE is more extensively metabolized than -T.

^* To whom correspondence should be addressed. E-mail: qjiang{at}purdue.edu.

Manuscript received 8 December 2008. Initial review completed 12 December 2008. Revision accepted 10 February 2009.

Published online 18 March 2009.