Absorption, metabolism, and excretion of (–)-epicatechin in humans: an evaluation of recent findings

Flavan-3-ols, such as (–)-epicatechin (I in Figure 1), and their oligomeric derivatives, procyanidins, are major components in the human diet and can occur in substantial amounts, especially in cocoa, tea, apples, red wine, and berries (1). There is a wealth of data linking consumption of such foods, most notably cocoabased products, with reduced incidences of morbidity and mortality from cardiovascular diseases (2). (–)-Epicatechin can, at least partially, be causally linked with the beneficial effects associated with consumption of flavan-3-ol– and procyanidin-rich foods (2, 3). Unraveling the mechanism by which (–)-epicatechin mediates these effects involves knowledge of the fate of flavan-3ols within the body after their ingestion. Although questions remain, human dietary intervention studies have shown that after oral intake, (–)-epicatechin is absorbed into the epithelium of the small intestine, where it undergoes phase 2 metabolism. Depending on the amount ingested, food matrix effects, and other factors (4), the main metabolites—(–)epicatechin-3#-glucuronide (II), (–)-epicatechin-3#-sulfate (III), and 3#-methyl-(–)-epicatechin-5-sulfate (IV)—reach their peak plasma concentration 1–3 h after intake (5, 6). Subsequent urinary excretion of these and other metabolites has ranged from 21% to 50% of (–)-epicatechin intake. In this issue of the Journal, Actis-Goretta et al (7) report on the intestinal absorption, metabolism, and excretion of (–)-epicatechin in humans based on the use of a Loc-I-gut intestinal perfusion technique, which has been used previously to investigate certain aspects of drug metabolism (8). A multilumen perfusion catheter was introduced into the small intestine and 3 balloons inflated to isolate two 20-cm sections of the jejunum. The upper balloon was positioned ;20 cm below the papilla of Vater. As a consequence, when (–)-epicatechin was introduced into the proximal and distal segments of the catheter, this enabled biliary excretion of flavan-3ols to be monitored by analysis of perfusates collected from the lumen above the upper balloon. Using 6 volunteers, 50 mg (172 lmol) of (–)-epicatechin was introduced into isolated jejunum sections, which were then perfused for 2.5 h. An average of 23.4 mg of unchanged (–)-epicatechin was recovered along with 0.84 mg of metabolites, indicative of low-level efflux of metabolites formed in the enterocytes back into the lumen of the jejunum. This finding shows that ;50% of the administered (–)-epicatechin was absorbed into the systemic circulation. Corroborating previous findings (4), (–)-epicatechin metabolites reached submicromolar peak plasma concentrations 1 h after the initiation of perfusion.