Modulation of aflatoxin biomarkers in human blood and urine by green tea polyphenols intervention.

To evaluate the efficacy of green tea polyphenols (GTPs) in modulating aflatoxin B(1) (AFB(1)) biomarkers, a total of 352 serum samples and 352 urine samples collected from a 3 month chemoprevention trial with 500 mg GTPs, 1000 mg GTPs and a placebo were measured for AFB(1)-albumin adducts (AFB-AA), aflatoxin M(1) (AFM(1)) and aflatoxin B(1)-mercapturic acid (AFB-NAC). Levels of AFB-AA at baseline were comparable for all three dose groups (P = 0.506). No significant differences were observed in AFB-AA levels in the placebo group over the 3 month period (P = 0.252). However, a significant reduction in AFB-AA levels was observed in the 500 mg group (P = 0.002). A marginally significant reduction in AFB-AA levels was also found in the 1000 mg group over the 3 month intervention period (P = 0.051). An analysis using a mixed-effects model indicated that the reduction in AFB-AA levels over time was dose and time dependent (dose-time interaction P = 0.049). There were no significant differences in median AFM(1) levels among the three study groups at the baseline (P = 0.832), 1 month (P = 0.188) and 3 months (P = 0.132) of the GTP intervention; however, reduction of 42 and 43% in median AFM(1) levels, as compared with the placebo, were found in 500 mg (P = 0.096) and 1000 mg (P = 0.072) groups at 3 months of the intervention. Significant elevations in median AFB-NAC levels and the ratio of AFB-NAC:AFM(1) were found in both 500 and 1000 mg groups compared with the placebo group at both 1 month (P < 0.001) and 3 months (P < 0.001) of GTPs intervention. These results demonstrate that GTPs effectively modulate AFB(1) metabolism and metabolic activation.

Validation of green tea polyphenol biomarkers in a phase II human intervention trial.

Health benefits of green tea polyphenols (GTPs) have been reported in many animal models, but human studies are inconclusive. This is partly due to a lack of biomarkers representing green tea consumption. In this study, GTP components and metabolites were analyzed in plasma and urine samples collected from a phase II intervention trial carried out in 124 healthy adults who received 500- or 1000-mg GTPs or placebo for 3 months. A significant dose-dependent elevation was found for (-)-epicatechin-3-gallate (ECG) (p<0.001, trend test) and (-)-epigallocatechin-3-gallate (EGCG) (p<0.05, trend test) concentrations in plasma at both 1-month and 3-months after intervention with GTPs. No significant increase of (-)-epicatechin (EC) or (-)-epigallocatechin (EGC) was observed in plasma after GTP intervention. A mixed-effects model indicated significant effects of dose (EGCG) and dose by time interaction (ECG), but not for EC and EGC. Analysis of phase 2 metabolic conjugates revealed a predominance of free GTPs in plasma, up to 85% for EGCG, while a majority of GTPs in urine were sulfated and glucuronidated conjugates (up to 100% for EC and 89% for EGC). These results suggest that plasma ECG and EGCG concentrations are reliable biomarkers for green tea consumption at the population level.

Phase IIa chemoprevention trial of green tea polyphenols in high-risk individuals of liver cancer: modulation of urinary excretion of green tea polyphenols and 8-hydroxydeoxyguanosine.

Modulation of urinary excretion of green tea polyphenols (GTPs) and oxidative DNA damage biomarker, 8-hydroxydeoxyguanosine (8-OHdG), were assessed in urine samples collected from a randomized, double-blinded and placebo-controlled phase IIa chemoprevention trial with GTP in 124 individuals. These individuals were sero-positive for both HBsAg and aflatoxin-albumin adducts, and took GTP capsules daily at doses of 500 mg, 1000 mg or a placebo for 3 months. Twenty-four hour urine samples were collected before the intervention and at the first and third month of the study. Urinary excretion of 8-OHdG and GTP components was measured by HPLC-CoulArray electrochemical detection. The baseline levels of 8-OHdG and GTP components among the three groups showed homogeneity (P > 0.70), and a non-significant fluctuation was observed in the placebo group over the 3 months (P > 0.30). In GTP-treated groups, epigallocatechin (EGC) and epicatechin (EC) levels displayed significant and dose-dependent increases in both the 500 mg group and 1000 mg group (P < 0.05). The 8-OHdG levels did not differ between the three groups at the 1 month collection, with medians of 1.83, 2.08 and 1.86 ng/mg-creatinine for placebo, 500 and 1000 mg group, respectively (P = 0.999). At the end of the 3 months' intervention, 8-OHdG levels decreased significantly in both GTP-treated groups, with medians of 2.02, 1.03 and 1.15 ng/mg-creatinine for placebo, 500 mg and 1000 mg group, respectively (P = 0.007). These results suggest that urinary excretions of EGC and EC can serve as practical biomarkers for green tea consumption in human populations. The results also suggest that chemoprevention with GTP is effective in diminishing oxidative DNA damage.