Identification of metabolite markers of long‐term green tea polyphenol intake in humans

Abstract

Green tea polyphenols (GTP) possess diverse bioactivities on cell proliferation and survival, but the metabolic impact of chronic GTP intake on humans was not well defined. In this study, fecal and urine samples from postmenopausal female subjects taking the GTP supplement or placebo for 12 months were analyzed by liquid chromatography‐mass spectrometry‐based metabolomics analysis. The metabolites associated with GTP treatment were first identified by multivariate modeling of control and treatment, and then characterized by structural elucidation and quantitative analysis. A group of phenolic acids derived from microbial metabolism of GTP were identified as the robust exposure markers. In contract, major GTP, such as epigallocatechin gallate (EGCG), were not found in significant amounts in feces, suggesting extensive biotransformation mediated by microflora. One of these microbial metabolites was determined as 3‐hydroxyphenylvaleric acid, which has not been identified as an EGCG metabolite in human feces previously. In urine samples, chronic GTP treatment led to the presence of sulfate and glucuronide metabolites of GTP, but decreased the levels of microbial metabolites phenylacetylglutamine and indoxyl sulfate. Interestingly, ascorbic acid was identified as one of urinary metabolites that were significantly decreased by GTP, indicating the influence of chronic GTP treatment on redox balance. Overall, these results suggest that specific microbial, xenobiotic, and endogenous metabolic events contribute to the formation of diverse markers of long‐term GTP intake.Support or Funding InformationNCI grant R01 CA127236NIFA project MIN‐18‐092