Chronic and Acute Effects of Green Tea Extract and Catechol-O-methyltransferase Genotype on Body Composition and Obesity-Associated Hormones in Overweight and Obese Postmenopausal Women

Abstract

This dissertation details the chronic and acute effects of green tea extract (GTE) supplementation (1315 mg green tea catechins/day, 843 mg as (-)-epigallocatechin-3-gallate, [EGCG]) on body composition, obesity-associated hormones, glucose homeostasis, and satiety in overweight and obese postmenopausal women at increased risk for breast cancer due to high mammographic density. Participants in the forthcoming studies were a subset of participants drawn from the Minnesota Green Tea Trial (MGTT), which was a randomized, placebo-controlled, double-blind, phase II clinical trial designed to determine the effects of supplementing GTE for one year on breast cancer risk factors including mammographic density, reproductive hormones, insulin-like growth factor (IGF) axis proteins, and F2-isoprostanes, a recognized biomarker of oxidative stress. Effect modification by catechol-O-methyltransferase (COMT), an enzyme involved in the metabolism of green tea catechins, estrogens, and norepinephrine, was also analyzed for all endpoints, due to its potential role in modulating the impact of GTE on breast cancer risk factors. Chapter 1 provides a brief introduction to the MGTT and the forthcoming chapters. Chapter 2 presents a review of the literature, providing context for the MGTT and ancillary studies. Chapter 3 describes the effect of GTE on anthropometric variables, obesity-associated hormones (leptin, ghrelin, adiponectin, and insulin) and markers of glucose homeostasis (blood glucose concentrations and the homeostasis measure of insulin resistance [HOMA-IR]) in 237 participants. In this study, no changes in energy intake or anthropometric measurements were observed in women taking GTE or placebo. Similarly, no changes were seen in circulating leptin, ghrelin, adiponectin, or glucose concentrations. However, among participants with baseline insulin ≥10 µIU/mL, there was a reduction in insulin concentration in the GTE group over 12 months compared to the placebo group and participants with baseline insulin < 10 µIU/mL in either group (P < 0.01). Participants with the homozygous high-activity (G/G) form of COMT showed significantly lower adiponectin and higher insulin concentrations at month 12 as compared to those with the low-activity (A/A) genotype, regardless of treatment group. Chapter 4 describes the more specific effects of GTE on body composition as measured by dual-energy x-ray absorptiometry (DXA), including total body fat, % body fat, region-specific adiposity, and bone mineral density (BMD) in 121 participants. These results were correlated with measures of leptin, adiponectin, and insulin. No changes in BMI, total fat mass, % body fat, or BMD were observed in women taking GTE compared to placebo; however, a reduction in visceral adipose tissue mass in GTE participants as compared to the placebo group nearly reached significance. Interactions were observed between treatment, time, and baseline BMI for gynoid % fat and tissue % fat, with more favorable results seen in the GTE group. No changes were seen in circulating leptin, adiponectin, or insulin concentrations. COMT genotype did not modify the effect of GTE on any variable. Chapter 5 details the acute postprandial effects of GTE administration in 60 participants who were administered a high-carbohydrate breakfast meal in the final months of their participation in the MGTT. Leptin, ghrelin, and adiponectin were not different between GTE and placebo at any time point and COMT genotype did not modify these results. Participants randomized to GTE with the high-activity form of the COMT enzyme (GTE-high COMT) had higher insulin concentrations immediately after the test meal (time 0) and at 0.5 and 1.0 hours post-meal compared to all COMT groups randomized to placebo. The GTE-high COMT group had higher insulin concentrations at times 0, 0.5, 1.0, 1.5, and 2.0 h compared to the GTE-low COMT group. Nine markers of satiety and appetite, as measured through comparison of mean area under the curve (cm/hr), were not different between GTE and placebo. The results of these three studies demonstrate that daily supplementation of 1315 mg GTE, independent of caffeine, does not influence long-term energy intake, satiety, body weight, or obesity-associated hormones, though it may be beneficial for individuals with a higher degree of visceral adiposity and with increased circulating insulin concentrations. This suggests benefit for those at risk for metabolic syndrome or type 2 diabetes. Given the association of these conditions with breast cancer risk, GTE may be a beneficial dietary supplement for overweight and obese postmenopausal women.