RESUMO
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.
Assuntos
Tecido Adiposo/efeitos dos fármacos , Composição Corporal/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Camellia sinensis/química , Suplementos Nutricionais , Obesidade/metabolismo , Extratos Vegetais/farmacologia , Tecido Adiposo/metabolismo , Adiposidade/efeitos dos fármacos , Índice de Massa Corporal , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Cafeína/farmacologia , Camellia sinensis/genética , Catequina/análogos & derivados , Catequina/farmacologia , Catecol O-Metiltransferase/genética , Método Duplo-Cego , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Obesidade/tratamento farmacológico , Sobrepeso , Pós-Menopausa , Chá/químicaRESUMO
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/m(2)]. 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 < 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.
Assuntos
Adiponectina/sangue , Catecol O-Metiltransferase/genética , Insulina/sangue , Obesidade/sangue , Sobrepeso/sangue , Chá/química , Administração Oral , Idoso , Glicemia/metabolismo , Índice de Massa Corporal , Peso Corporal , Cafeína/administração & dosagem , Cafeína/análise , Catequina/administração & dosagem , Catequina/análogos & derivados , Método Duplo-Cego , Ingestão de Energia , Jejum , Feminino , Genótipo , Grelina/sangue , Humanos , Leptina/sangue , Pessoa de Meia-Idade , Atividade Motora , Avaliação Nutricional , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem , Pós-Menopausa , Circunferência da CinturaRESUMO
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 1 year. Annual digital screening mammograms were obtained at baseline and month 12, and fasting blood and 24-h urine samples were provided at baseline and at 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 1,075 participants based on treatment (green tea extract vs. placebo), stratified by COMT genotype activity (high COMT vs. low/intermediate COMT genotype activity). A total of 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.
Assuntos
Biomarcadores/metabolismo , Neoplasias da Mama/prevenção & controle , Mama/anatomia & histologia , Mamografia , Chá , Antioxidantes/administração & dosagem , Catequina/administração & dosagem , Catequina/análogos & derivados , Catecol O-Metiltransferase/genética , Método Duplo-Cego , Estrogênios/urina , F2-Isoprostanos/sangue , Feminino , Genótipo , Hormônios Esteroides Gonadais/sangue , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Pessoa de Meia-Idade , Minnesota , Estresse Oxidativo , Fatores de RiscoRESUMO
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 P < 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. Cancer Prev Res; 10(10); 571-9. ©2017 AACR.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/sangue , Suplementos Nutricionais/efeitos adversos , Fígado/efeitos dos fármacos , Extratos Vegetais/efeitos adversos , Chá/química , Idoso , Alanina Transaminase/sangue , Antioxidantes/efeitos adversos , Aspartato Aminotransferases/sangue , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/prevenção & controle , Catequina/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Método Duplo-Cego , Feminino , Humanos , Fígado/enzimologia , Testes de Função Hepática , Pessoa de Meia-Idade , Placebos , Extratos Vegetais/química , Estados UnidosRESUMO
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 (P = 0.05), but had no effect in older women (Pinteraction = 0.07). GTE supplementation did not induce MD change in other subgroups of women stratified by catechol-O-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. Cancer Prev Res; 10(12); 710-8. ©2017 AACR.
Assuntos
Densidade da Mama/efeitos dos fármacos , Neoplasias da Mama/prevenção & controle , Suplementos Nutricionais , Extratos Vegetais/farmacologia , Chá/química , Idoso , Anticarcinógenos/farmacologia , Antioxidantes/administração & dosagem , Índice de Massa Corporal , Mama/efeitos dos fármacos , Catequina/análogos & derivados , Catequina/farmacologia , Catecol O-Metiltransferase/genética , Método Duplo-Cego , Feminino , Genótipo , Humanos , Mamografia , Pessoa de Meia-Idade , Pós-Menopausa , Tamoxifeno/farmacologiaRESUMO
Green tea is thought to provide health benefits, though adverse reactions to green tea extract (GTE) have been reported. We conducted a randomized, double-blind, placebo-controlled study of GTE on breast cancer biomarkers, including mammographic density, in which 1075 postmenopausal women were randomly assigned to consume GTE containing 843 mg (-)-epigallocatechin-3-gallate (EGCG) or placebo daily for one year. There were no significant differences in % of women with adverse events (AEs, 75.6% and 72.8% of the GTE group and placebo group, respectively) or serious AEs (2.2 % and 1.5% of GTE and placebo groups, respectively). Women on GTE reported significantly higher incidence of nausea (P < 0.001) and dermatologic AEs (P = 0.05) and significantly lower diarrhea incidence (P = 0.02). More women in the GTE group experienced an alanine aminotransferase (ALT) elevation compared with placebo group (n = 36, (6.7%) vs. n = 4, (0.7%); P < 0.001). There were no statistically significant differences between groups in frequencies of other AEs. Overall, AEs were mainly mild and transient, indicating that daily consumption of GTE containing 843 mg EGCG is generally well tolerated by a group of predominantly Caucasian postmenopausal women. However, 6.7% of GTE consumers experienced ALT elevations, with 1.3% experiencing ALT-related serious AEs.