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

University of Minnesota Ph.D. dissertation. June 2015. Major: Nutrition. Advisor: Mindy Kurzer. 1 computer file (PDF); xiii, 177 pages.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

Long-term supplementation of green tea extract does not modify adiposity or bone mineral density in a randomized trial of overweight and obese postmenopausal women

Background: Green tea extract (GTE) consumption has been linked to favorable changes in adiposity and bone mineral density (BMD), although it is unknown if these effects are due to green tea catechins or caffeine. The catechol-Omethyltransferase (COMT) genotype may also modify these associations. Objective: We examined the impact of decaffeinated GTE on body composition (using dual-energy X-ray absorptiometry) and obesity-associated hormones. Methods: The Minnesota Green Tea Trial was a 12-mo randomized, double-blind, placebo-controlled clinical trial in 937 postmenopausal women (aged 50-70 y) assigned to receive either GTE containing 843 mg (2)-epigallocatechin-3-gallate or placebo. This substudy was conducted in 121 overweight/obese participants [body mass index (BMI) (kg/m2) $25.0]. Results: Therewere no differences in changes in BMI (20.13 6 0.11 compared with -0.05 ± 0.11; P = 0.61), total fatmass (-0.30 ± 0.16 compared with -0.12 ± 0.15 kg; P = 0.40), percentage of body fat (-0.15% ± 0.17% compared with 20.15% ± 0.16%; P = 0.99), or BMD (20.006 ± 0.002 compared with -0.003 ± 0.002 g/cm2; P = 0.49) over 12 mo between women taking GTE (n = 61) and those taking a placebo (n = 60). Interactions were observed between treatment and time for gynoid percentage of fat (%fat) and tissue%fat. Gynoid%fat increased frombaseline tomonth 12 in the placebo group as baseline BMI increased and decreased over time as baseline BMI increased in the GTE group (P-interaction = 0.02). Tissue %fat increased from baseline to month 12 in the placebo group as baseline BMI increased. In the GTE group, tissue %fat decreased during the intervention as baseline BMI increased (P-interaction = 0.04). No changeswere seen in circulating leptin, ghrelin, adiponectin, or insulin concentrations. COMT genotype did not modify the effect of GTE on any variable. Conclusions: Decaffeinated GTE was not associated with overall reductions in adiposity or improvements in BMD in overweight/obese postmenopausal women. However, GTE may be beneficial for reduction in tissue and gynoid%fat in individuals with higher BMI. This clinical trial was registered at www.clinicaltrials.gov as NCT00917735

Long-Term Supplementation of Green Tea Extract Does Not Modify Adiposity or Bone Mineral Density in a Randomized Trial of Overweight and Obese Postmenopausal Women

Background: Green tea extract (GTE) consumption has been linked to favorable changes in adiposity and bone mineral density (BMD), although it is unknown if these effects are due to green tea catechins or caffeine. The catechol-O-methyltransferase (COMT) genotype may also modify these associations. Objective: We examined the impact of decaffeinated GTE on body composition (using dual-energy X-ray absorptiometry) and obesity-associated hormones. Methods: The Minnesota Green Tea Trial was a 12-mo randomized, double-blind, placebo-controlled clinical trial in 937 postmenopausal women (aged 50–70 y) assigned to receive either GTE containing 843 mg (−)-epigallocatechin-3-gallate or placebo. This substudy was conducted in 121 overweight/obese participants [body mass index (BMI) (kg/m(2)) ≥25.0]. Results: There were no differences in changes in BMI (−0.13 ± 0.11 compared with −0.05 ± 0.11; P = 0.61), total fat mass (−0.30 ± 0.16 compared with −0.12 ± 0.15 kg; P = 0.40), percentage of body fat (−0.15% ± 0.17% compared with −0.15% ± 0.16%; P = 0.99), or BMD (−0.006 ± 0.002 compared with −0.003 ± 0.002 g/cm(2); P = 0.49) over 12 mo between women taking GTE (n = 61) and those taking a placebo (n = 60). Interactions were observed between treatment and time for gynoid percentage of fat (%fat) and tissue %fat. Gynoid %fat increased from baseline to month 12 in the placebo group as baseline BMI increased and decreased over time as baseline BMI increased in the GTE group (P-interaction = 0.02). Tissue %fat increased from baseline to month 12 in the placebo group as baseline BMI increased. In the GTE group, tissue %fat decreased during the intervention as baseline BMI increased (P-interaction = 0.04). No changes were seen in circulating leptin, ghrelin, adiponectin, or insulin concentrations. COMT genotype did not modify the effect of GTE on any variable. Conclusions: Decaffeinated GTE was not associated with overall reductions in adiposity or improvements in BMD in overweight/obese postmenopausal women. However, GTE may be beneficial for reduction in tissue and gynoid %fat in individuals with higher BMI. This clinical trial was registered at www.clinicaltrials.gov as NCT00917735

Green Tea Extract and Catechol-O-Methyltransferase Genotype Modify Fasting Serum Insulin and Plasma Adiponectin Concentrations in a Randomized Controlled Trial of Overweight and Obese Postmenopausal Women

Background: Green tea consumption has been associated with favorable changes in body weight and obesity-related hormones, although it is not known whether these changes result from green tea polyphenols or caffeine. Objective: We examined the impact of decaffeinated green tea extract (GTE) containing 843 mg of (−)-epigallocatechin-3-gallate on anthropometric variables, obesity-associated hormones, and glucose homeostasis. Methods: The Minnesota Green Tea Trial was a 12-mo randomized, double-blind, placebo-controlled clinical trial of 937 healthy postmenopausal women assigned to either decaffeinated GTE (1315 mg total catechins/d) or a placebo, stratified by catechol-O-methyltransferase (COMT) genotype. This study was conducted in a subset of 237 overweight and obese participants [body mass index (BMI) ≥25 kg/m2]. Results: No changes in energy intake, body weight, BMI, or waist circumference (WC) were observed over 12 mo in women taking GTE (n = 117) or placebo (n = 120). No differences were seen in circulating leptin, ghrelin, adiponectin, or glucose concentrations at month 12. Participants randomly assigned to GTE with baseline insulin ≥10 μIU/mL (n = 23) had a decrease in fasting serum insulin from baseline to month 12 (−1.43 ± 0.59 μIU/mL), whereas those randomly assigned to placebo with baseline insulin ≥10 μIU/mL (n = 19) had an increase in insulin over 12 mo (0.55 ± 0.64 μIU/mL, P \u3c 0.01). Participants with the homozygous high-activity (G/G) form of COMT had significantly lower adiponectin (5.97 ± 0.50 compared with 7.58 ± 0.53 μg/mL, P = 0.03) and greater insulin concentrations (7.63 ± 0.53 compared with 6.18 ± 0.36 μIU/mL, P = 0.02) at month 12 compared with those with the low-activity (A/A) genotype, regardless of treatment group. Conclusions: Decaffeinated GTE was not associated with reductions in body weight, BMI, or WC and did not alter energy intake or mean hormone concentrations in healthy postmenopausal women over 12 mo. GTE decreased fasting insulin concentrations in those with elevated baseline fasting concentrations. The high-activity form of the COMT enzyme may be associated with elevations in insulin and a reduction in adiponectin concentrations over time. This trial was registered at http://www.clinicaltrials.gov as NCT00917735