Hepatotoxicity with High-Dose Green Tea Extract: Effect of Catechol-O-Methyltransferase and Uridine 5'-Diphospho-glucuronosyltransferase 1A4 Genotypes

J Diet Suppl. 2023;20(6):850-869. doi: 10.1080/19390211.2022.2128501. Epub 2022 Sep 30.


The predominant catechin in green tea, epigallocatechin gallate (EGCG), may be hepatotoxic in high doses. Our objective was to investigate the influence of catechol-O-methyltransferase (COMT) and uridine 5'-diphospho-glucuronosyltransferase 1A4 (UGT1A4) genotypes on changes in liver injury biomarkers in response to long-term, high-dose green tea extract (GTE) supplementation among postmenopausal women. A secondary analysis was conducted using data from the Minnesota Green Tea Trial (N = 1,075), in which participants were randomized to consume high-dose GTE (843 mg/day EGCG) or placebo capsules for 12 months. Analysis of covariance adjusting for potential confounders was performed to examine changes in aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST: ALT ratio, and alkaline phosphatase from baseline to months 3, 6, 9, and 12 across COMT and UGT1A4 genotypes. Mean age and BMI within the GTE group (n = 400) were 59.8 yrs and 25.1 kg/m2, respectively, and 98% of subjects were white. From baseline to month 3, mean AST: ALT ratio change was +1.0% in the COMT (rs4680) A/G genotype versus -4.8% in the A/A genotype (p = 0.03). From baseline to months 6 and 9, respectively, mean ALT change was +78.1% and +82.1% in the UGT1A4 (rs6755571) A/C genotype versus +28.0% and +30.1% in the C/C genotype (p < 0.001 and p = 0.004, respectively). The UGT1A4 (rs6755571) A/C genotype may be an important risk factor for clinically-relevant serum transaminase elevations with 6-9 months of high-dose GTE supplementation among postmenopausal women. Understanding the genetic underpinnings of GTE-related hepatotoxicity may allow for a genetically-informed paradigm for therapeutic use of GTE.

Keywords: Camellia sinensis; alanine transaminase; aspartate aminotransferases; catechol O-methyltransferase; chemical and drug induced liver injury; epigallocatechin gallate; glucuronosyltransferase; tea.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Antioxidants
  • Catechin*
  • Catechol O-Methyltransferase / genetics
  • Chemical and Drug Induced Liver Injury* / genetics
  • Dietary Supplements
  • Female
  • Genotype
  • Glucuronosyltransferase / genetics
  • Humans
  • Plant Extracts* / toxicity
  • Tea / toxicity


  • Antioxidants
  • Catechin
  • Catechol O-Methyltransferase
  • Glucuronosyltransferase
  • Plant Extracts
  • Tea
  • COMT protein, human
  • bilirubin glucuronoside glucuronosyltransferase