Intestinal absorption, metabolism, and excretion of (-)-epicatechin in healthy humans assessed by using an intestinal perfusion technique.

BACKGROUND (-)-Epicatechin is a dietary flavonoid present in many foods that affects vascular function, but its action is limited by incomplete absorption, conjugation, and metabolism. Factors that influence this activity may be attributed to instability in the gastrointestinal lumen, low permeability across the intestinal wall, or active efflux from enterocytes and extensive conjugation. OBJECTIVE With the use of a multilumen perfusion catheter, we investigated the jejunal absorption, systemic availability, metabolism, and intestinal, biliary, and urinary excretion of (-)-epicatechin in humans. DESIGN In a single-center, randomized, open, controlled study in 8 healthy volunteers, 50 mg purified (-)-epicatechin was perfused into an isolated jejunal segment together with antipyrine as a marker for absorption. (-)-Epicatechin and conjugates were measured in intestinal perfusates, bile, plasma, and urine. RESULTS Forty-six percent of the dose was recovered in the perfusate either as unchanged (-)-epicatechin (22 mg) or conjugates (0.8 mg); with stability taken into account, this result indicates that ∼46% of the dose had apparently been absorbed. The conjugates were predominantly sulfates, which indicated conjugation by sulfotransferases followed by efflux from the enterocytes. In contrast, epicatechin glucuronides were dominant in plasma, bile, and urine. CONCLUSIONS Almost one-half of the (-)-epicatechin is apparently absorbed in the jejunum but with substantial interindividual differences in the extent of absorption. The data suggest that the nature and substitution position of (-)-epicatechin conjugation are major determinants of the metabolic fate in the body, influencing whether the compound is effluxed into the lumen or absorbed into the blood and subsequently excreted.