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.

Purpose The Minnesota Green Tea Trial (MGTT) was a randomized, placebo-controlled, double-blinded trial investigating the effect of daily green tea extract consumption for 12 months on biomarkers of breast cancer risk. Methods Participants were healthy postmenopausal women at high risk of breast cancer due to dense breast tissue with differing catechol-O-methyltransferase (COMT) genotypes. The intervention was a green tea catechin extract containing 843.0 ± 44.0 mg/day epigallocatechin gallate or placebo capsules for one year. Annual digital screening mammograms were obtained at baseline and month 12, and fasting blood and 24-hour urine samples were provided at baseline, months 6, and 12. Primary endpoints included changes in percent mammographic density, circulating endogenous sex hormones and insulin-like growth factor axis proteins; secondary endpoints were changes in urinary estrogens and estrogen metabolites and circulating F2-isoprostanes, a biomarker of oxidative stress. Results The MGTT screened more than 100,000 mammograms and randomized 1075 participants based on treatment (green tea extract vs. placebo), stratified by COMT genotype activity (high COMT vs. low/intermediate COMT genotype activity). 937 women successfully completed the study and 138 dropped out (overall dropout rate= 12.8%). Conclusions In this paper we report the rationale, design, recruitment, participant characteristics, and methods for biomarker and statistical analyses.

Epidemiologic and animal studies suggest a protective role of green tea against breast cancer. However, the underlying mechanism is not understood. We conducted a randomized, double-blinded, placebo-controlled phase II clinical trial to investigate whether supplementation with green tea extract (GTE) modifies mammographic density (MD), as a potential mechanism, involving 1,075 healthy postmenopausal women. Women assigned to the treatment arm consumed daily 4 decaffeinated GTE capsules containing 1,315 mg total catechins, including 843 mg epigallocatechin-3-gallate (EGCG) for 12 months. A computer-assisted method (Madena) was used to assess MD in digital mammograms at baseline and month 12 time points in 932 completers (462 in GTE and 470 in placebo). GTE supplementation for 12 months did not significantly change percent MD (PMD) or absolute MD in all women. In younger women (50-55 years), GTE supplementation significantly reduced PMD by 4.40% as compared with the placebo with a 1.02% PMD increase from pre- to postintervention ( = 0.05), but had no effect in older women ( = 0.07). GTE supplementation did not induce MD change in other subgroups of women stratified by catechol--methyltransferase genotype or level of body mass index. In conclusion, 1-year supplementation with a high dose of EGCG did not have a significant effect on MD measures in all women, but reduced PMD in younger women, an age-dependent effect similar to those of tamoxifen. Further investigation of the potential chemopreventive effect of green tea intake on breast cancer risk in younger women is warranted. .

The objective of this study was to monitor adverse events (AEs) in healthy postmenopausal women randomized to receive either green tea extract (GTE) containing 840 mg (‐)‐epigallocatechin‐3‐gallate (EGCG)/day (n=538) or placebo (n=537) for one year. Data on AEs was obtained by participant self‐report and hepatic panel assessment. AEs were recorded and graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), v.4.03. 407 participants in the GTE group reported 1141 AEs; 391 participants in the placebo group reported 1031 AEs. Infections and infestations were the most common AEs (139 GTE vs. 145 placebo participants, p = 0.67) followed by gastrointestinal (GI) disorders (137 GTE vs. 123 placebo participants, p = 0.33). Nausea incidence was higher in GTE participants (55 (10.2%) vs. 26 (4.8%), p < 0.001). Diarrhea incidence was lower in the GTE group (24 (4.5%) vs. 43 (8%) participants, p = 0.02). More participants taking GTE reported dermatologic AEs (18 (3.3%) vs. 8 (1.5%), p = 0.05). Alanine aminotransferase (ALT) elevations were seen in 36 (6.7%) GTE vs. 4 (0.7%) placebo participants (p < 0.001). Twenty‐six serious adverse events (CTCAE grades 3‐5) occurred in 12 GTE vs. 8 placebo participants (p = 0.37). GTE containing 840 mg EGCG/day was associated with mainly mild, transient AEs and was well tolerated by most participants, though an association with GI and hepatic abnormalities was confirmed. This project was supported by the NIH/NCI.

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.

Liver injury effects of green tea-based products have been reported in sporadic case reports. However, no study has examined systematically such adverse effects in an unbiased manner. We examined the potential effects of a high, sustained oral dose of green tea extract (GTE) on liver injury measures in a randomized, placebo-controlled, double-blinded phase II clinical trial, which enrolled 1,075 women with the original aim to assess the effect of daily GTE consumption for 12 months on biomarkers of breast cancer risk. The current analysis examined the effect of GTE consumption on liver injury in 1,021 participants (513 in GTE and 508 in placebo arm) with normal baseline levels of liver enzymes. Among women in the GTE arm, alanine aminotransferase (ALT) increased by 5.4 U/L [95% confidence interval (CI), 3.6-7.1] and aspartate aminotransferase increased by 3.8 U/L (95% CI, 2.5-5.1), which were significantly higher than those among women in the placebo arm (both < 0.001). Overall, 26 (5.1%) women in GTE developed moderate or more severe abnormalities in any liver function measure during the intervention period, yielding an OR of 7.0 (95% CI, 2.4-20.3) for developing liver function abnormalities as compared with those in the placebo arm. ALT returned to normal after dechallenge and increased again after one or more rechallenges with GTE. The rise-fall pattern of liver enzyme values following the challenge-dechallenge cycles of GTE consumption strongly implicates the effect of high-dose GTE on liver enzyme elevations. .

Our study confirms the relationship between BMI and long-term colorectal cancer mortality. Modulation of BMI may reduce risk of CRC mortality.

Background Green tea extract (GTE) may be involved in a favorable postprandial response to high-carbohydrate meals. Catechol-O-methyltransferase (COMT) genotype may modify these effects. We examined the acute effects of GTE supplementation on postprandial response to a high-carbohydrate meal through assessing appetite-associated hormones and glucose homeostasis marker concentrations in women who consumed 843 mg (−)-epigallocatechin-3-gallate [EGCG]) or placebo capsules for 11-12 months. Methods Sixty Caucasian postmenopausal women (BMI ≥ 25.0 kg/m2) were included in a randomized, double-blind feeding study. GTE was consumed with a breakfast meal (665.4 kcal; 67.2% carbohydrate). Blood samples were drawn pre-meal, post-meal, and every 30 minutes for 4 h. Participants completed six satiety questionnaires. Results Plasma leptin, ghrelin, and adiponectin did not differ between GTE and placebo at any time point; COMT genotype did not modify these results. Participants randomized to GTE with the high-activity form of COMT (GTE-high COMT) had higher insulin concentrations at time 0, 0.5, and 1.0 h post-meal compared to all COMT groups randomized to placebo. Insulin remained higher in the GTE-high COMT group at 1.5, 2.0, and 2.5 h compared to Placebo-low COMT (P < 0.02). GTE-high COMT had higher insulin concentrations at times 0, 0.5, 1.0, 1.5, and 2.0 h compared to the GTE-low COMT (P ≤ 0.04). AUC measurements of satiety did not differ between GTE and placebo. Conclusions GTE supplementation and COMT genotype did not alter acute postprandial responses of leptin, ghrelin, adiponectin, or satiety, but may be involved in post-meal insulinemic response of overweight and obese postmenopausal women.