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J. Nutr. (March 18, 2009). doi:10.3945/jn.108.103309
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© 2009 American Society for Nutrition


Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions

{gamma}-Tocotrienol and {gamma}-Tocopherol Are Primarily Metabolized to Conjugated 2-(β-carboxyethyl)-6-Hydroxychroman and Sulfated Long-Chain Carboxychromanols in Rats1,2,3

Helene Freiser and Qing Jiang*

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

The metabolism of {gamma}-tocotrienol ({gamma}-TE) and {gamma}-tocopherol ({gamma}-T) was investigated in human A549 cells and in rats. Similar to {gamma}-T, A549 cells metabolized {gamma}-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 {gamma}-TE, but <45% from {gamma}-T, were in the sulfated form. The formation of these metabolites was further investigated in rats gavaged by {gamma}-TE at 10 or 50 mg/kg, {gamma}-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 {gamma}-TE–supplemented rats. Sulfatase/glucuronidase hydrolysis revealed for the first time that >88% 2-(β-carboxyethyl)-6-hydroxychroman ({gamma}-CEHC), the terminal β-oxidation metabolite, was in the conjugated form in the plasma. In all groups, conjugated {gamma}-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 {gamma}-TE–supplemented rats were higher (P < 0.05) than those from {gamma}-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 {gamma}-TE is more extensively metabolized than {gamma}-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.







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