Hepatotoxicity with High-Dose Green Tea Extract: Effect of Catechol-O-Methyltransferase and Uridine 5'-Diphospho-glucuronosyltransferase 1A4 Genotypes.
Laura Acosta, Laura Byham-Gray, Mindy Kurzer, Hamed Samavat
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引用次数: 0
Abstract
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.
期刊介绍:
The Journal of Dietary Supplements (formerly the Journal of Nutraceuticals, Functional & Medical Foods) has been retitled to reflect the bold departure from a traditional scientific journal presentation to a leading voice for anyone with a stake in dietary supplements. The journal addresses important issues that meet the broad range of interests from researchers, regulators, marketers, educators, and health professionals from academic, governmental, industry, healthcare, public health, and consumer education sectors. This vital tool not only presents scientific information but interprets it - helping you more readily pass it on to your students, patients, clients, or company.