Acute Dose-Response Effectiveness of Combined Catechins and Chlorogenic Acids on Postprandial Glycemic Responses in Healthy Men: Results from Two Randomized Studies.

Epidemiologic studies show that the risk of diabetes can be reduced by ingesting green tea or coffee. Previous studies have shown that simultaneously taking green tea catechins (GTC) and coffee chlorogenic acid (CCA) alters postprandial gastrointestinal hormones secretion and improves insulin sensitivity. However, there is no evidence on the acute effects of GTC and CCA on incretin and blood glucose, and on the respective dose of polyphenols. In this randomized, double-blind, placebo-controlled crossover study, we examined the effective dose of GTC and CCA on postprandial glucose, insulin, and incretin responses to a high-fat and high-carbohydrate cookie meal containing 75 g of glucose in healthy men. Study 1 (n = 18) evaluated two doses of GTC (270 or 540 mg) containing a fixed dose of CCA (270 mg) with 113 mg of caffeine and a placebo (0 mg GTC and 0 mg CCA) with 112 mg of caffeine. Study 2 (n = 18) evaluated two doses of CCA (150 or 300 mg) containing a fixed dose of GTC (540 mg) and a placebo with 99 mg of caffeine. The single combined ingestion of GTC and CCA significantly altered the incretin response and suppressed glucose and insulin levels. These findings suggest that the effective minimum dose is 540 mg of GTC and 150 mg of CCA.

Effects of Ingesting Both Catechins and Chlorogenic Acids on Glucose, Incretin, and Insulin Sensitivity in Healthy Men: A Randomized, Double-Blinded, Placebo-Controlled Crossover Trial.

Epidemiologic studies have revealed that consuming green tea or coffee reduces diabetes risk. We evaluated the effects of the combined consumption of green tea catechins and coffee chlorogenic acids (GTC+CCA) on postprandial glucose, the insulin incretin response, and insulin sensitivity. Eleven healthy men were recruited for this randomized, double-blinded, placebo-controlled crossover trial. The participants consumed a GTC+CCA-enriched beverage (620 mg GTC, 373 mg CCA, and 119 mg caffeine/day) for three weeks; the placebo beverages (PLA) contained no GTC or CCA (PLA: 0 mg GTC, 0 mg CCA, and 119 mg caffeine/day). Postprandial glucose, insulin, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) responses were measured at baseline and after treatments. GTC+CCA consumption for three weeks showed a significant treatment-by-time interaction on glucose changes after the ingestion of high-fat and high-carbohydrate meals, however, it did not affect fasting glucose levels. Insulin sensitivity was enhanced by GCT+CCA compared with PLA. GTC+CCA consumption resulted in a significant increase in postprandial GLP-1 and a decrease in GIP compared to PLA. Consuming a combination of GTC and CCA for three weeks significantly improved postprandial glycemic control, GLP-1 response, and postprandial insulin sensitivity in healthy individuals and may be effective in preventing diabetes.

Effect of Catechins on Upper Respiratory Tract Infections in Winter: A Randomized, Placebo-Controlled, Double-Blinded Trial.

Tea catechins are plant-derived compounds that improve immune functions. Previous randomized control trials have demonstrated the efficacy of primarily epi-type catechins against upper respiratory tract infections (URTIs). Green tea can be consumed in several ways, including popular bottled beverages. These beverages, however, require sterilization during manufacturing, which results in catechin isomerization. We conducted a randomized, double-blinded, placebo-controlled trial involving healthy Japanese participants to evaluate whether catechin consumption via bottled beverages has an alleviating effect on the duration and severity of URTIs in winter. The catechin group (490 mg catechin, 0.14%, containing 59% epi-type catechin, n = 55) showed reduced durations of running nose, nasal congestion, and headache, compared with the placebo group (0 mg catechin, n = 54; p = 0.013, 0.018, and <0.001, respectively). Furthermore, when considering physical symptoms, the duration of nasopharyngeal symptoms improved significantly in the catechin group (p < 0.001) compared with that in the control group. The daily consumption of catechin thus reduced the duration and severity of URTIs in healthy men and women. Humans are regularly exposed to several potential infectious threats, and the oral administration of heat-epimerized tea catechins might help prevent and reduce the severity of URTIs.

Concomitant use of tea catechins affects absorption and serum triglyceride-lowering effects of monoglucosyl hesperidin.

The present study investigated whether combined ingestion of green tea catechins (GTC) and monoglucosyl hesperidin (GHES) influences the pharmacokinetic parameters of polyphenols and serum triglycerides (TG). We conducted 2 randomized, controlled trials. Study 1: 8 healthy male subjects participated in a crossover study in which they ingested a test beverage containing GHES (0, 84, 168, or 336 mg GHES) with GTC, or 336 mg GHES without GTC. After ingestion, the pharmacokinetic changes in plasma hesperetin (HEP) and catechins were measured. Study 2: 36 healthy male and female subjects (mean age, 53 ± 2 years; mean BMI, 25.2 ± 0.5 kg m-2) were recruited for a double-blind, placebo-controlled study in which they ingested a test beverage containing 165 mg GHES with 387 mg GTC or a placebo beverage daily for 4 weeks. Fasting serum TG and other lipids and glucose metabolites were analyzed. Study 1 showed that the pharmacokinetics of HEP did not differ significantly between the 336 mg GHES without GTC treatment and the 168 mg GHES with GTC treatment. Study 2 showed that continuous ingestion of 165 mg GHES and 387 mg GTC for 4 weeks significantly decreased fasting serum TG levels compared with baseline values (change in TG, -30 ± 13 mg dl-1, P = 0.040) in the intention-to-treat analysis. In conclusion, our findings suggest that GTC affects the oral bioavailability of GHES, and combined ingestion of low doses of GHES with GTC effectively improves fasting TG levels.

Preventive effects of tea and tea catechins against influenza and acute upper respiratory tract infections: a systematic review and meta-analysis.

PURPOSE: Gargling with tea has protective effects against influenza infection and upper respiratory tract infection (URTI). To evaluate if tea and tea catechin consumption has the same protective effects as gargling with tea, we performed a systematic review and meta-analysis. METHODS: We performed a comprehensive literature search using the PubMed, Cochrane Library, Web of Science, and Ichu-shi Web databases. The search provided six randomized controlled trials (RCTs) and four prospective cohort studies (n = 3748). The quality of each trial or study was evaluated according to the Cochrane risk-of-bias tool or Newcastle-Ottawa Scale. We collected data from publications meeting the search criteria and conducted a meta-analysis of the effect of tea gargling and tea catechin consumption for preventing URTI using a random effects model. RESULTS: Tea gargling and tea catechin consumption had significant preventive effects against URTI (risk ratio [RR] = 0.74, 95% confidence interval [CI] 0.64-0.87). In sub-analyses, a significant preventive effect was observed by study type (prospective cohort study: RR = 0.67, 95% CI 0.50-0.91; RCT: RR = 0.79, 95% CI 0.66-0.94) and disease type (influenza: RR = 0.69, 95% CI 0.58-0.84; acute URTI: RR = 0.78, 95% CI 0.62-0.98). Both gargling with tea and consuming tea catechins effectively protected against URTI (tea and tea catechins consumption: RR = 0.68, 95% CI 0.52-0.87; tea gargling: RR = 0.83, 95% CI 0.72-0.96). CONCLUSION: Our findings suggest that tea gargling and tea catechin consumption may have preventive effects against influenza infection and URTI. The potential effectiveness of these actions as non-pharmaceutical interventions, however, requires further investigation.

Effects of Timing of Acute and Consecutive Catechin Ingestion on Postprandial Glucose Metabolism in Mice and Humans.

We examined the effects of the timing of acute and consecutive epigallocatechin gallate (EGCG) and catechin-rich green tea ingestion on postprandial glucose in mice and human adults. In mouse experiments, we compared the effects of EGCG administration early (morning) and late (evening) in the active period on postprandial glucose. In human experiments, participants were randomly assigned to the morning-placebo (MP, n = 10), morning-green tea (MGT, n = 10), evening-placebo (EP, n = 9), and evening-green tea (EGT, n = 9) groups, and consumed either catechin-rich green tea or a placebo beverage for 1 week. At baseline and after 1 week, participants consumed their designated beverages with breakfast (MP and MGT) or supper (EP and EGT). Venous blood samples were collected in the fasted state and 30, 60, 120, and 180 min after each meal. Consecutive administration of EGCG in the evening, but not in the morning, reduced postprandial glucose at 30 (p = 0.006) and 60 (p = 0.037) min in the evening trials in mice. In humans, ingestion of catechin-rich green tea in the evening decreased postprandial glucose (three-factor analysis of variance, p < 0.05). Thus, catechin intake in the evening more effectively suppressed elevation of postprandial glucose.

Effect of tea catechins with caffeine on energy expenditure in middle-aged men and women: a randomized, double-blind, placebo-controlled, crossover trial.

PURPOSE: It has been reported that tea catechins increase energy metabolism, but their effect on resting metabolic rate (RMR) remains under debate. This study aimed to examine the effect of repeated intake of tea catechins on energy metabolism in the resting state in middle-aged men and women. METHODS: A total of 30 middle-aged men and women [13 women; age (mean ± SD) 52 ± 4 years; BMI 21.9 ± 2.2 kg/m2] were recruited. A randomized, double-blind, crossover study was conducted using a tea catechin-enriched beverage (611 mg catechins, 88 mg caffeine) and a placebo beverage (0 mg catechins, 81 mg caffeine) as test beverages. After 2 weeks of continuous test beverage intake, fasting RMR and energy expenditure (EE) after the ingestion of test beverage were measured. Measurements of forehead temperature (proxy for core temperature) and skin temperature were also obtained simultaneously. RESULTS: Among participants who underwent measurements, 26 (10 women; mean age 52 ± 4 years; mean BMI 22.1 ± 2.1 kg/m2) were analyzed. The EE increased significantly after ingestion of the tea catechin beverage compared with the placebo beverage (placebo treatment: 5502 ± 757 kJ/day; catechin treatment: 5598 ± 800 kJ/day; P = 0.041). No between-treatment differences in fasting RMR or the respiratory quotient were detected. In addition, the forehead and skin temperature did not differ significantly between the placebo and catechin treatments. CONCLUSION: This study revealed that continuous intake of tea catechins with caffeine for 2 weeks significantly increased EE after ingestion of the tea catechin but not fasting RMR in middle-aged men and women. CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE: This trial was registered at www.umin.ac.jp/ctr/ as UMIN000025810 and UMIN000025811.

Prevention of Acute Upper Respiratory Infections by Consumption of Catechins in Healthcare Workers: A Randomized, Placebo-Controlled Trial.

Catechins, phytochemicals contained mainly in green tea, exhibit antiviral activity against various acute infectious diseases experimentally. Clinical evidence supporting these effects, however, is not conclusive. We performed a placebo-controlled, single-blind, randomized control trial to evaluate the clinical effectiveness of consumption of catechins-containing beverage for preventing acute upper respiratory tract infections (URTIs). Two hundred and seventy healthcare workers were randomly allocated to high-catechin (three daily doses of 57 mg catechins and 100 mg xanthan gum), low-catechin (one daily dose of 57 mg catechins and 100 mg xanthan gum), or placebo (0 mg catechins and 100 mg xanthan gum) group. Subjects consumed a beverage with or without catechins for 12 weeks from December 2017 through February 2018. The primary endpoint was incidence of URTIs compared among groups using a time-to-event analysis. A total of 255 subjects were analyzed (placebo group n = 86, low-catechin group n = 85, high catechin group n = 84). The URTI incidence rate was 26.7% in the placebo group, 28.2% in the low-catechin group, and 13.1% in the high-catechin group (log rank test, p = 0.042). The hazard ratio (95% confidence interval (CI)) with reference to the placebo group was 1.09 (0.61-1.92) in the low-catechin group and 0.46 (0.23-0.95) in the high-catechin group. These findings suggest that catechins combined with xanthan gum protect against URTIs.

Effects of timing of acute catechin-rich green tea ingestion on postprandial glucose metabolism in healthy men.

Green tea polyphenols, particularly catechins, decrease fasting and postprandial glucose. However, no studies have compared the timing of green tea ingestion on glucose metabolism and changes in catechin concentrations. Here, we examined the effects of timing of acute catechin-rich green tea ingestion on postprandial glucose metabolism in young men. Seventeen healthy young men completed four trials involving blood collection in a fasting state and at 30, 60, 120, and 180 min after meal consumption in a random order: 1) morning placebo trial (09:00 h; MP trial), 2) evening placebo trial (17:00 h; EP trial), 3) morning catechin-rich green tea trial (09:00 h; MGT trial), and 4) evening catechin-rich green tea trial (17:00 h; EGT trial). The concentrations of glucose at 120 min (P=.031) and 180 min (P=.013) after meal intake were significantly higher in the MGT trials than in the MP trials. Additionally, the concentration of glucose was significantly lower in EGT trials than in the EP trials at 60 min (P=.014). Moreover, the concentrations of glucose-dependent insulinotropic polypeptide were significantly lower in the green tea trials than in the placebo trials at 30 min (morning: P=.010, evening: P=.006) and 60 min (morning: P=.001, evening: P=.006) after meal intake in both the morning and evening trials. Our study demonstrated that acute ingestion of catechin-rich green tea in the evening reduced postprandial plasma glucose concentrations.

Coffee Abundant in Chlorogenic Acids Reduces Abdominal Fat in Overweight Adults: A Randomized, Double-Blind, Controlled Trial.

The components of roasted or green coffee beans that promote abdominal fat reduction are not clear. We investigated the effects of daily consumption of coffee enriched in chlorogenic acids (CGA) on abdominal fat area in a randomized, double-blind, parallel controlled trial. Healthy, overweight men and women (n = 150, body mass index (BMI) ≥25 to <30 kg/m2) were randomly allocated to high-CGA (369 mg CGA/serving) or control (35 mg CGA/serving) coffee groups. Instant coffee was consumed once daily for 12 weeks, with four-week pre- and post-observation periods. Abdominal fat area and anthropometric measurements were analyzed at baseline and at four, eight, and 12 weeks, and 142 subjects completed the trial. Visceral fat area (VFA), total abdominal fat area (TFA), body weight, and waist circumference significantly decreased in the CGA group compared with the control group, with a group × time interaction (p < 0.001, p = 0.001, p = 0.025, and p = 0.001, respectively). Changes in VFA and TFA from baseline to 12 weeks were significantly greater in the CGA group than in the control group (-9.0 ± 13.9 cm2 vs. -1.0 ± 14.3 cm2, p < 0.001; -13.8 ± 22.9 cm2 vs. -2.0 ± 16.2 cm2, p < 0.001). No severe adverse events occurred. Consumption of high-CGA coffee for 12 weeks by overweight adults might lower VFA, TFA, BMI, and waist circumference.

Coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone improves postprandial endothelial dysfunction in patients with borderline and stage 1 hypertension.

PURPOSE: The purpose of this study was to evaluate acute effects of coffee with a high content of chlorogenic acids and different hydroxyhydroquinone contents on postprandial endothelial dysfunction. METHODS: This was a single-blind, randomized, placebo-controlled, crossover-within-subject clinical trial. A total of 37 patients with borderline or stage 1 hypertension were randomized to two study groups. The participants consumed a test meal with a single intake of the test coffee. Subjects in the Study 1 group were randomized to single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone or coffee with a high content of chlorogenic acids and a high content of hydroxyhydroquinone with crossover. Subjects in the Study 2 group were randomized to single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone or placebo coffee with crossover. Endothelial function assessed by flow-mediated vasodilation and plasma concentration of 8-isoprostanes were measured at baseline and at 1 and 2 h after coffee intake. RESULTS: Compared with baseline values, single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone, but not coffee with a high content of chlorogenic acids and high content of hydroxyhydroquinone or placebo coffee, significantly improved postprandial flow-mediated vasodilation and decreased circulating 8-isoprostane levels. CONCLUSIONS: These findings suggest that a single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone is effective for improving postprandial endothelial dysfunction. CLINICAL TRIAL REGISTRATION: URL for Clinical Trial: https://upload.umin.ac.jp ; Registration Number for Clinical Trial: UMIN000013283.

Efficacy of tea catechin-rich beverages to reduce abdominal adiposity and metabolic syndrome risks in obese and overweight subjects: a pooled analysis of 6 human trials.

This post hoc pooled analysis assessed the effectiveness of green tea catechins (GTC) to reduce the risk of metabolic syndrome (MetS) associated with abdominal fat reduction, because previous findings are unclear. Data were pooled from six human trials (n=921, 505 men) comparing the effects of GTC-containing beverages (540-588 mg GTC/beverage) and a placebo beverage. Outcome measures were abdominal fat [total fat area (TFA), visceral fat area (VFA), subcutaneous fat area (SFA)], and MetS risk. We estimated mean changes from baseline and calculated confidence intervals (CI) to assess reductions in abdominal fat accumulation and MetS improvement. Subclass analyses were performed by classifying subjects as Pre-MetS or MetS at trial initiation. Additional subclass analyses were performed with Pre-MetS and MetS subjects further stratified according to whether GTC intake reduced TFA, VFA, or SFA. Consumption of GTC-containing beverages for 12 weeks significantly reduced TFA (-17.7cm2, 95%CI: -20.9 to -14.4), VFA (-7.5cm2, 95%CI: -9.3 to -5.7), SFA (-10.2cm2, 95%CI: -12.5 to -7.8), body weight, body mass index, and waist circumference; and improved blood pressure. Subclass analyses of Pre-MetS and MetS subjects showed improved MetS in the GTC group [odds ratio (OR), 1.67; 95%CI: 1.08-2.57]. The ORs for improved MetS in the TFA- and VFA-reduced groups were 2.79 (95%CI: 1.28-6.09) and 4.36 (95%CI: 2.03-9.39), respectively. Continual consumption of GTC-containing beverages reduced abdominal fat and improved MetS, suggesting its potential to prevent diabetes and cardiovascular disease. Additional large-scale intervention trials are needed to evaluate the effects of GTC on the risk of MetS in high-risk populations.

Effects of subacute ingestion of chlorogenic acids on sleep architecture and energy metabolism through activity of the autonomic nervous system: a randomised, placebo-controlled, double-blinded cross-over trial.

Chlorogenic acids (CGA) are the most abundant polyphenols in coffee. Continuous consumption of CGA reduces body fat and body weight. Since energy metabolism and sleep are controlled by common regulatory factors, consumption of CGA might modulate sleep. Lack of sleep has been identified as a risk factor for obesity, hypertension and type 2 diabetes. The aim of this study was to determine the effects of ingesting CGA over 5 d on energy metabolism and sleep quality in humans. A total of nine healthy subjects (four male and five female) completed a placebo-controlled, double-blinded, cross-over intervention study. Subjects consumed a test beverage containing 0 or 600 mg of CGA for 5 d. On the fifth night, subjects stayed in a whole-room metabolic chamber to measure energy metabolism; sleep was evaluated using polysomnographic recording. It was found that CGA shortened sleep latency (9 (sem 2) v. 16 (sem 4) min, P<0·05) compared with the control, whereas no effect on sleep architecture, such as slow-wave sleep, rapid eye movement or waking after sleep onset, was observed. Indirect calorimetry revealed that consumption of CGA increased fat oxidation (510 (sem 84) kJ/8 h (122 (sem 20) kcal/8 h) v. 331 (sem 79) kJ/8 h (81 (sem 19) kcal/8 h), P<0·05) but did not affect energy expenditure during sleep. Consumption of CGA enhanced parasympathetic activity assessed from heart-rate variability during sleep (999 (sem 77) v. 919 (sem 54), P<0·05). A period of 5-d CGA consumption significantly increased fat oxidation during sleep, suggesting that beverages containing CGA may be beneficial to reduce body fat and prevent obesity. Consumption of CGA shortened sleep latency and did not adversely affect sleep quality.

Tea catechin and caffeine activate brown adipose tissue and increase cold-induced thermogenic capacity in humans.

Background: The thermogenic effects of green tea catechin have been repeatedly reported, but their mechanisms are poorly understood.Objective: The aim of this study was to investigate the acute and chronic effects of catechin on brown adipose tissue (BAT), a site specialized for nonshivering thermogenesis, in humans.Design: Fifteen healthy male volunteers underwent fluorodeoxyglucose-positron emission tomography to assess BAT activity. To examine the acute catechin effect, whole-body energy expenditure (EE) after a single oral ingestion of a beverage containing 615 mg catechin and 77 mg caffeine (catechin beverage) was measured. Next, to investigate the chronic catechin effects, 10 men with low BAT activity were enrolled. Before and after ingestion of the catechin beverage 2 times/d for 5 wk, cold-induced thermogenesis (CIT) after 2 h of cold exposure at 19°C, which is proportional to BAT activity, was examined. Both the acute and chronic trials were single-blinded, randomized, placebo-controlled, season-matched crossover studies.Results: A single ingestion of the catechin beverage increased EE in 9 subjects who had metabolically active BAT (mean ± SEM: +15.24 ± 1.48 kcal, P < 0.01) but not in 6 subjects who had negligible activities (mean ± SEM: +3.42 ± 2.68 kcal). The ingestion of a placebo beverage containing 82 mg caffeine produced a smaller and comparative EE response in the 2 subject groups. Multivariate regression analysis revealed a significant interaction between BAT and catechin on EE (ß = 0.496, P = 0.003). Daily ingestion of the catechin beverage elevated mean ± SEM CIT (from 92.0 ± 26.5 to 197.9 ± 27.7 kcal/d; P = 0.009), whereas the placebo beverage did not change it.Conclusion: Orally ingested tea catechin with caffeine acutely increases EE associated with increased BAT activity and chronically elevates nonshivering CIT, probably because of the recruitment of BAT, in humans. These trials were registered at www.umin.ac.jp/ctr/ as UMIN000016361.

Effectiveness and safety of 1-year ad libitum consumption of a high-catechin beverage under nutritional guidance.

BACKGROUND: It has been reported that a continuous intake of a catechin beverage will reduce body fat. Traditionally, improvement of eating and exercise habits has been the basis for prevention and reduction of obesity. In this study, we conducted a trial involving human subjects who ingested a catechin beverage for 1 year under nutritional guidance. METHODS: This study was conducted based on a comprehensive cohort design using a catechin beverage (containing 588 mg of tea catechins) and a control beverage (containing 126 mg of tea catechins). At both the start and the end of the trial, the subjects underwent an annual health check and computer tomography for measurement of their abdominal fat. In addition, a food intake survey was conducted and all subjects were provided nutritional guidance by a registered dietitian every 3 months. RESULTS: Data were analyzed using per protocol samples of 134 subjects (catechin group, n = 77; control group, n = 57). Body weight and body mass index were reduced significantly in the catechin group compared to the control group. Changes in body weight during the study period were -1.1 kg in the catechin group and 0.2 kg in the control group. In the catechin group, the visceral fat areas at the start of the trial were significantly correlated with the magnitude of fat reduction at the end of the trial. Under the guidance of a registered dietitian, subjects in the catechin group who showed a reduction in their fat-derived energy percentage during the test period tended to reduce more body weight than those with an increase in this percentage, although no difference in total energy intake was noted between the two groups. One-year ad libitum consumption of a catechin beverage posed no health risks and resulted in a reduction in body weight. CONCLUSIONS: An overall improvement in dietary habits might enhance the weight-reduction effect of the beverage.