Joanna Kalina Hodges, PhD

Catechins in green tea extract (GTE) (epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin (EC), epicatechin gallate (ECG)) vary in bioactivity. We developed a physiologically relevant mathematical model of catechin metabolism to test the hypothesis that fractional catabolic rates of catechins would be differentially affected by their structural attributes. Pharmacokinetic data of plasma and urine catechin concentrations were used from healthy adults (n = 19) who ingested confections containing 0.5 g GTE (290 mg EGCG, 87 mg EGC, 39 mg EC, 28 mg ECG). A 7-compartmental model of catechin metabolism comprised of the gastrointestinal tract (stomach, small and large intestine), liver, plasma, extravascular tissues, and kidneys was developed using a mean fraction dose of EGCG, ECG, EGC, and EC. Fitting was by iterative least squares regression analysis, and goodness of fit was ascertained by the estimated variability of parameters (FSD < 0.5). The interaction of gallation and B-ring dihydroxylation most greatly extended plasma residence time such that EGC > EC = EGCG > EGC. The interaction between gallation and B-ring dihydroxylation accelerated the transfer from the upper gastrointestinal tract to the small intestine but delayed subsequent transfers from the small intestine through the liver to plasma and from kidneys to urine. Gallation and B-ring dihydroxylation independently delayed the transfer from plasma to extravascular tissues, except the uptake to kidneys, which was slowed by gallation only. This multi-compartment model, to be validated in a future study, suggests that gallation and B-ring dihydroxylation affect catechin catabolism in a tissue-specific manner and thus their potential bioactivity.