Tissue Distribution Of Vitamin E Metabolites In Rats After Oral Administration Of Tocopherol Or Tocotrienol

We previously found that 2,7,8-trimethyl-2(2'-carboxyethyl)-6-hydroxychroman (gamma CEHC), a metabolite of the vitamin E isoforms gamma-tocopherol or gamma-tocotrienol, accumulated in the rat small intestine. The aim of this study was to evaluate tissue distribution of vitamin E metabolites. A single dose of alpha-tocopherol, gamma-tocopherol or a tocotrienol mixture containing alpha- and gamma-tocotrienol was orally administered to rats. Total amounts of conjugated and unconjugated metabolites in the tissues were measured by HPLC with an electrochemical detector, and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (trolox) was used as an internal standard. Twenty-four hours later, the vitamin E isoforms were detected in most tissues and in the serum. However, 2,5,7,8-tetramethyl-2(2'-carboxyethyl)-6-hydroxychroman (alpha CEHC), a metabolite of alpha-tocopherol or alpha-tocotrienol, and gamma CEHC accumulated in the serum and in some tissues including the liver, small intestine and kidney. Administration of alpha-tocopherol increased the gamma CEHC concentration in the small intestine, suggesting that alpha-tocopherol enhances gamma-tocopherol catabolism. In contrast, ketoconazole, an inhibitor of cytochrome P450 (CYP)-dependent vitamin E catabolism, markedly decreased the gamma CEHC concentration. These data indicate that vitamin E metabolite accumulates not only in the liver but also in the small intestine and kidney. We conclude that some dietary vitamin E is catabolized to carboxyethyl-hydroxychroman in the small intestine and is secreted into the circulatory system.