Effects of green tea catechins with or without caffeine on glycemic control in adults : a meta-analysis of randomized controlled trials 1 – 4

Background: The effect of green tea catechins (GTCs) with or without caffeine on glycemic control is controversial. Objective: We aimed to identify and quantify the effects of GTCs or GTC-caffeine mixtures on glucose metabolism in adults. Design: A comprehensive literature search was conducted to identify relevant trials of GTCs with or without caffeine on markers of glycemic control [fasting blood glucose (FBG), fasting blood insulin (FBI), glycated hemoglobin (Hb A1c), and homeostatic model assessment of insulin resistance (HOMA-IR)]. Weighted mean differences were calculated for net changes by using fixed-effects models. Prespecified subgroup analyses were performed to explore the influence of covariates on net changes in FBG and FBI concentrations. Results: Twenty-two eligible randomized controlled trials with 1584 subjects were identified. Pooled analyses showed that FBG (21.48 mg/dL; 95% CI: 22.57, 20.40 mg/dL) decreased significantly with GTCs with or without caffeine, whereas FBI (0.04 mU/mL; 95% CI: 20.36, 0.45 mU/mL), Hb A1c (20.04%; 95% CI: 20.15, 0.08%), and HOMA-IR (20.05; 95% CI: 20.37, 0.26) did not. Subgroup analyses indicated that the glucose-lowering effect was apparent when the duration of follow-up was over a median of 12 wk. Overall, no significant heterogeneity was detected for FBG, FBI, Hb A1c, or HOMA-IR. Conclusions: The meta-analysis showed that the administration of GTCs with or without caffeine resulted in a significant reduction in FBG. The limited data available on GTCs did not support a positive effect on FBI, Hb A1c, or HOMA-IR. Thus, more large and welldesigned trials are needed in the future. This trial was registered at http://www.crd. york.ac. uk/prospero as CRD42012002139. Am J Clin Nutr 2013;97:750–62. INTRODUCTION Type 2 diabetes is increasing rapidly in prevalence throughout the world and is seriously affecting human health because of its high disability rate and mortality (1, 2). The appropriate management of hyperglycemia by changing dietary patterns is particularly important in primary, secondary, and tertiary diabetes prevention (3). Recently, beverages have been identified as an important modifier of diabetes risk (4, 5), and the effects of green tea on diabetes have received increasing attention in view of the accumulated encouraging findings from experimental research (6, 7). Green tea, an enriched source of flavonoids, is consumed worldwide. Green tea catechins (GTCs) constitute w80–90% of the total flavonoids, and these catechins include catechin, epicatechin, epigallocatechin, epicatechin-3-gallate, epigallocatechin gallate (EGCG), gallocatechin, catechin gallate, and gallocatechin gallate (8). EGCG, the most pharmacologically active molecule of GTC, has been shown to have antidiabetic effects (9). Green tea also naturally contains caffeine, which may be beneficial in the prevention of diabetes through increased energy expenditure or increased thermogenesis (6, 10). Observational studies have shown that high frequency of green tea consumption was associated with improved glycemic control and reduced risk of type 2 diabetes (6, 7). In vitro and in vivo studies have shown that EGCG exerted antihyperglycemic effects via multiple mechanisms involving certain pathways: 1) inhibition of carbohydrate digestive enzyme activity, 2) inhibition of hepatic gluconeogenesis by decreased expression of gluconeogenic genes, 3) enhancement of insulin sensitivity and insulin-like activity, and 4) improvement of oxidative stress (11–14). Evidence from animal and observational studies has supported that GTCs with or without caffeine may benefit glycemic control, but intervention studies in humans have yielded inconsistent results (15–36). Some studies showed that catechins significantly improved glycemic control (21–23, 25, 27, 31, 34–36), whereas others observed no significant antihyperglycemic effect (15–20, 24, 26, 28–30, 32, 33). As a result, the precise effect of green tea on glucose metabolism has not been established to our knowledge. Therefore, we conducted a meta-analysis of all published 1 From the Department of Cardiology and Key Laboratory for Clinical Cardiovascular Genetics & Sino-German Laboratory for Molecular Medicine, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China (X-XZ, Y-LX, RH, Y-JW, and X-HH), and the Department of Cardiology, Provincial Hospital Affiliated to Shandong University, Jinan, China (S-HL). 2 X-XZ and Y-LX contributed equally to this article. 3 Supported by the Ministry of Science and Technology of China with a grant from the National High-Rech Research and Development Program of China (to X-HH). 4 Address correspondence to X-H Huang or Y-J Wu, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Beijing, People’s Republic of China 100037. E-mail: huangxhong12@gmail.com or fuwaihospital@gmail.com. Abbreviations used: EGCG, epigallocatechin gallate; FBG, fasting blood glucose; FBI, fasting blood insulin; GTC, green tea catechin; Hb A1c, glycated hemoglobin; RCT, randomized controlled trial. ReceivedDecember 21, 2011. Accepted for publication December 21, 2012. First published online February 20, 2013; doi: 10.3945/ajcn.111. 032573. 750 Am J Clin Nutr 2013;97:750–62. Printed in USA. 2013 American Society for Nutrition D ow naded rom http/academ ic.p.com /ajcn/article-ct/97/4/750/4577040 by gest on 02 M arch 2019 randomized controlled trials (RCTs) to quantitatively evaluate the effects of GTCs with or without caffeine on such glycemic control measurements as fasting blood glucose (FBG), fasting blood insulin (FBI), glycated hemoglobin (Hb A1c), and HOMA-IR.