Abstract
Objectives
The predominant catechins [epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin (EC), epicatechin gallate (ECG)] in green tea extract (GTE) vary in bioactivity. Our objective was to develop a physiologically relevant mathematical model of catechin metabolism and assess their fractional catabolic rates relative to their structural attributes, which may influence their bioactivities.
Methods
Pharmacokinetic data were collected from healthy adults (n = 18; 27 ± 7 y; 22 ± 2 kg/m2) after oral intake of 0.5 g GTE (EGCG: 290 mg, EGC: 87 mg, EC: 39 mg, ECG: 28 mg) delivered in 3 gelatin-based confections. Participants maintained a low-polyphenol diet for 3 d prior to the trial. Concentrations of deconjugated catechins were measured by LC-MS in plasma and urine collected at timed intervals over 12 and 24 h, respectively. A multi-compartment model of catechin metabolism was developed using the mean fraction of dose for all catechins. Data were fitted by iterative least squares regression analysis in WinSAAM software. Kinetic parameters for EGCG and EGC were compared using a Student t-test and one-way ANOVA.
Results
Observed data for each catechin were successfully fit into a 7-compartment model comprised of the gastrointestinal tract (stomach, small and large intestine), liver, plasma, extravascular tissues, and kidneys. Goodness of fit was ascertained by the estimated variability of parameters (FSD < 0.5). Based on plasma response profiles, EGC and EC disappeared from plasma faster compared with EGCG and ECG. The highest fractional uptake was by the extravascular tissues (P < 0.05) with no other between-organ differences. Compared with EGCG, EGC showed a higher fractional transfer from the liver to plasma (2.5 vs. 0.4 pools/h, P < 0.001) and the uptake by kidneys (1.2 vs. 0.01 pools/h, P < 0.001) with no difference in absorption. The fractional catabolic rate was also higher for EGC compared with EGCG (59.4 vs. 42.7 plasma pools/h, P < 0.05), while its plasma transit time was shorter (0.9 vs. 1.3 min, P < 0.05).
Conclusions
A 7-compartment model, to be validated in a future study, was successfully developed to demonstrate that EGC is eliminated faster compared with EGCG in healthy adults, suggesting that the gallate group may influence relative bioactivity of catechins.
Funding Sources
The Ohio State University and the National Institute of Food and Agriculture.