In order to investigate the impact of common food ingredients on catechin absorption, green tea (GT) extract (50 mg) was formulated plain, with sucrose (GT+S), with ascorbic acid (GT+AA) and with sucrose and ascorbic acid (GT+S+AA). Bioavailability and bioaccessibility were assessed in Sprague Dawley rats and an in vitro digestion/Caco-2 cell model respectively. Absorption of epigallocatechin (EGC) and epigallocatechin gallate (EGCG) was significantly (P<0.05) enhanced in GT+S+AA formulations (AUC0-6h= 3237.0 and 181.8 pmol*h/L plasma respectively) relative to GT control (AUC0-6h = 1304.1 and 61.0 pmol*h/L plasma respectively). In vitro digestive recovery was higher for EGC and epicatechin (EC) (∼51-53%) relative to EGCG and epicatechin gallate (ECG) (< 20%) and was modestly enhanced in GT+S and GT+S+AA formulations. Accumulation of EGC, EGCG and ECG by Caco-2 cells was significantly (P<0.05) higher from GT+S+AA compared to other formulations while retention of catechins was enhanced in presence of ascorbic acid. These data suggest that formulation with sucrose and ascorbic acid may improve catechin bioavailability by enhancing bioaccessibility and intestinal uptake from tea.

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Formation of homo‐ and hetero‐dimers through auto‐oxidation of epigallocatechin gallate (EGCG) and epigallocatechin (EGC) under simulated digestion has been reported. However, little data exists regarding potential absorption of these dimers. The objective of this study was to first demonstrate intestinal absorption of these dimers in vitro in order to characterize their potential relevance in vivo. Dimers generated by pH‐induced (pH 7.0) auto‐oxidation of catechin reactants (0.3 mM) in saline were incubated on highly differentiated Caco‐2 cell monolayers for 3 h. HPLC analysis of cell extracts with electrochemical array detection and MS/MS characterization indicated the presence of the EGCG homodimers theasinensin (m/z 913) and P‐2 (m/z 883) as well as Phase‐II conjugated metabolites of EGC homodimers (m/z 689 and 593) in the cells. These results indicate that catechin auto‐oxidation dimers formed through food processing or potentially through digestive reactions may be absorbed by human intestinal epithelial cells. Furthermore, catechin dimers appear to be substrates for the Phase‐II detoxification pathways known to metabolize monomeric catechins. These observations suggest that the potential digestive formation and subsequent absorption of catechin auto‐oxidation dimers in vivo warrants further investigation. (Supported by NIH grant CA119210‐01A1).

Green tea (GT) catechins are antioxidants which have many potential health benefits. Their bioavailability has previously been evaluated only by plasma pharmacokinetics, but target tissue concentrations are likely more important to delivery of specific health benefits. The aim of this study was to demonstrate the relationship between plasma and ISF pharmacokinetics of catechins from GT. Sprague Dawley rats were implanted with ultrafiltrate probes, for sampling of ISF, and femoral catheters. Rats were dosed by oral gavage with 50 mg of GT extract and 10 mg ascorbic acid. The ascorbic acid was added to increase bioavailability. Blood samples were collected at baseline and 0.5, 1, 2, 4, 6, and 8 hours. ISF was collected two hours before gavage and every two hours post gavage for 16 hours. Catechins in the plasma and ISF were extracted with 0.01 % butylated hydroxytoluene in ethyl acetate and analyzed by HPLC. The results showed that epigallocatechin peaked in the plasma between one and two hours and epicatechin peaked in the plasma at half‐an‐hour. Both catechins peaked in ISF about two hours post gavage. This data suggests that plasma and ISF pharmacokinetics may not be the same for all catechins. Some catechins may provide benefits to target tissues for a longer duration of time than indicated by plasma pharmacokinetics. Supported by NIH, Office of Dietary Supplements and NCCAM Grant P50 AT 00477.

To characterize the impact of green tea formulation on catechin bioavailability, 50 mg of green tea (GT) extract providing 3.8, 1.8, 1.5, and 2.5 micromoles of epicatechin (EC), epigallocatechin (EGC), epigallocatechin gallate (EGCG) and epicatechin gallate (ECG) respectively was formulated plain (GT), with sucrose (GTS, 1.3g), and with sucrose plus ascorbic acid (GTS+AA, 10mg). Catechin digestive stability and intestinal uptake were assessed using a coupled in vitro digestion/Caco‐2 cell model. In vivo bioavailability was investigated in Sprague Dawley rats by 6h oral pharmacokinetic (PK) study. Catechin levels were measured by RPC18 HPLC. Addition of AA significantly (p<0.05) increased catechin in vitro digestive recovery (20 to >75%) with greatest impact on EGC (5 to >90%) and EGCG (6 to >61%). Caco‐2 intracellular accumulation of EGC was significantly increased to 70 pmol/mg protein by formulation with AA, compared to undetectable levels in GTS formulations. In vivo plasma PK data suggest that bioavailability of digestively labile EGCG and EGC may be enhanced by formulation with AA (AUC= 310 and 2671 nmol/mL respectively) relative to controls (AUC = 195 and 2346 nmol/L respectively). These data provide evidence that formulation factors impact both digestive recovery and may influence intestinal absorption of catechins from tea beverages in vivo. (Supported by NIH NCCAM grant P50‐AT00477)