Combination of Quercetin and Green Tea Extract Increased Plasma Epicatechingallate and Decreased Urine Epigallocatechin and Epicatechin Concentrations

Abstract

Preclinical studies have shown that the combination of quercetin (Q) and green tea (GT) extract enhanced the anti‐carcinogenic activity in a prostate cancer xenograft model, increased the bioavailability of GT polyphenols (P) and decreased P methylation compared to GT extract alone. In order to test the hypothesis in humans that Q in combination with GT extract would enhance bioavailability of GTP compared to GT extract consumption alone we enrolled 32 men diagnosed with prostate cancer and randomized them to receive 2 capsules of GT extract (240 mg) in combination with either 1 capsule of Q (400 mg) (GT+Q) or placebo (GT+PL) two times per day prior to prostatectomy. Blood and early morning spot urine were collected at baseline and at 3 weeks. Bioavailability of GTP and Q were tested at 3 weeks by sampling before and 2 hours after administration of GT and Q. Immediately after the surgery a small aliquot of prostate tissue was collected. All urine, blood and tissue samples were analyzed for GTP and Q by high performance liquid chromatography with coularray detection and mass‐spectrometry. Red blood cell (RBC) and prostate gene expression, protein expression and DNA and polyphenol methylation enzyme activity were determined. There was no liver toxicity in any subject. Q was increased 14‐fold, 12‐fold and 4.5‐fold in plasma, urine, and prostate tissue, respectively, in subjects given GT+Q by comparison to GT+PL. Plasma ECG was significantly increased in men consuming GT+Q compared to GT+PL consistent with an effect of Q on bioavailability of GT as previously observed in animals. Urinary excretion of EGC, 4'‐MeEGC and EC was significantly decreased in urine collected prior to surgery in participants consuming GT+Q compared to GT+PL. The percent of methylated EGC tended to increase from 36 to 79% in urine from men consuming GT+Q compared to GT+PL (p=0.137). ECG and/or EGCG were found in the prostate tissue of 31 out of 32 participants, but there was no difference in prostate GTP content between the GT+Q and GT+PL groups. There were also no epigenetic differences in prostate or RBC as determined by catechol‐methyltransferase and DNA‐methyltransferase gene and protein expression and enzyme activity. Further investigations are underway to determine whether the presence of quercetin in addition to GT polyphenols in the prostate modulated inflammation or oxidant stress in prostate tissue.Support or Funding InformationNIH RO3CA171583