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

Following ingestion of [2-¹⁴C](-)-epicatechin by rats, radioactivity in urine, feces, body fluids and tissues collected over a 72h period, was measured and ¹⁴C-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 1h after intake corresponding 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 6-12h was predominantly in the form of the ring fission metabolites 5-(3',4'-dihydroxyphenyl)-γ-valerolactone and 5-(3',4'-dihydroxyphenyl)-γ-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-O-glucuronide and 3'-O-methyl-(-)-epicatechin-5-O-glucuronide with small amounts of (-)-epicatechin, 3'-O-methyl-(-)-epicatechin, 5-(3'-hydroxyphenyl)-γ-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.