Hepatotoxicity with High-Dose Green Tea Extract: Effect of Genotypes.

The predominant catechin in green tea, epigallocatechin gallate (EGCG), may be hepatotoxic in high doses. Our objective was to investigate the influence of () and () 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 ( = 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 and genotypes. Mean age and BMI within the GTE group ( = 400) were 59.8 yrs and 25.1 kg/m, respectively, and 98% of subjects were white. From baseline to month 3, mean AST: ALT ratio change was +1.0% in the (rs4680) genotype versus -4.8% in the genotype ( = 0.03). From baseline to months 6 and 9, respectively, mean ALT change was +78.1% and +82.1% in the (rs6755571) genotype versus +28.0% and +30.1% in the genotype ( < 0.001 and  = 0.004, respectively). The (rs6755571) 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.