A comprehensive evaluation of the [2-14C](-)-epicatechin metabolome in rats

Following ingestion of [2-C-14](-)-epicatechin by rats, radioactivity in urine, feces, body fluids and tissues collected over a 72 h period, was measured and C-14-metabolites were analyzed by HPLC-MS2 with a radioactivity monitor. In total 78% of the ingested radioactivity was absorbed from the gastrointestinal tract (GIT), and then rapidly eliminated from the circulatory system via renal excretion. A peak plasma concentration occurred 1 h after intake corresponding to similar to 0.7% of intake. Low amounts of radioactivity, < 2% of intake, appeared transiently in body tissues. Glucuronidation and methylation of (-)-epicatechin began in the duodenum but occurred more extensively in the jejunum/ileum. Radioactivity reaching the cecum after 6-12 h was predominantly in the form of the ring fission metabolites 5-(3',4'-dihydroxyphenyl)-y-valerolactone and 5-(3',4'-dihydroxyphenyl)-y-hydroxyvaleric acid along with smaller amounts of their phase II metabolites. Low levels of metabolites were detected in the colon. Of the ingested radioactivity, 19% was voided in feces principally as ring-fission metabolites. The main components in plasma were (-)-epicatechin 5 0 glucuronide and 3' 0 methyl (-) epicatechin 5 0 glucuronide with small amounts of (-)-epicatechin, 3'-0-methyl (-) epicatechin, 5-(3'-hydroxyphenyl)-y-hydroxyvaleric acid-4'-glucuronide and hippuric acid also being detected. No oxidized products of (-)-epicatechin were detected. No compelling evidence was obtained for biliary recycling of metabolites. The findings demonstrate substantial differences in the metabolism of (-)-epicatechin by rats and humans. Caution should, therefore, be exercised when using animal models to draw conclusions about effects induced by (-)-epicatechin intake in humans. (C) 2016 Elsevier B.V. All rights reserved.