Catechin-rich Green Tea Research Articles

A green tea extract confection decreases circulating endotoxin and fasting glucose by improving gut barrier function but without affecting systemic inflammation: A double-blind, placebo-controlled randomized trial in healthy adults and adults with metabolic syndrome

Anti-inflammatory activities of catechin-rich green tea extract (GTE) in obese rodents protect against metabolic endotoxemia by decreasing intestinal permeability and absorption of gut-derived endotoxin. However, translation to human health has not been established. We hypothesized that GTE would reduce endotoxemia by decreasing gut permeability and intestinal and systemic inflammation in persons with metabolic syndrome (MetS) compared with healthy persons. A randomized, double-blind, placebo-controlled, crossover trial in healthy adults (n = 19, 34 ± 2 years) and adults with MetS (n = 21, 40 ± 3 years) examined 4-week administration of a decaffeinated GTE confection (890 mg/d total catechins) on serum endotoxin, intestinal permeability, gut and systemic inflammation, and cardiometabolic parameters. Compared with the placebo, the GTE confection decreased serum endotoxin (P = .023) in both healthy persons and those with MetS, while increasing concentrations of circulating catechins (P < .0001) and γ-valerolactones (P = .0001). Fecal calprotectin (P = .029) and myeloperoxidase (P = .048) concentrations were decreased by GTE regardless of health status. Following the ingestion of gut permeability probes, urinary lactose/mannitol (P = .043) but not sucralose/erythritol (P > .05) was decreased by GTE regardless of health status. No between-treatment differences (P > .05) were observed for plasma aminotransferases, blood pressure, plasma lipids, or body mass nor were plasma tumor necrosis factor-α, interleukin-6, or the ratio of lipopolysaccharide-binding protein/soluble cluster of differentiation-14 affected. However, fasting glucose in both study groups was decreased (P = .029) by the GTE confection compared with within-treatment arm baseline concentrations. These findings demonstrate that catechin-rich GTE is effective to decrease circulating endotoxin and improve glycemic control in healthy adults and those with MetS, likely by reducing gut inflammation and small intestinal permeability but without affecting systemic inflammation.

The intestinal-level metabolic benefits of green tea catechins: Mechanistic insights from pre-clinical and clinical studies

BackgroundThe intestinal-level host-microbiota interaction has been implicated in the pathogenesis of chronic diseases. The current review is intended to provide a comprehensive insight into deciphering whether intestinal-level bioactivities mediate the overall metabolic health benefits of green tea catechins. PurposeWe have comprehensively discussed pre-clinical and clinical evidences of intestinal-level changes in metabolism, microbiota, and metabolome due to catechin-rich green tea treatments, ultimately limiting metabolic diseases. Exclusive emphasis has been given to purified catechins and green tea, and discussions on extraintestinal mechanisms of metabolic health benefits were avoided. MethodsA literature search for relevant pre-clinical and clinical studies was performed in various online databases (e.g., PubMed) using specific keywords (e.g., catechin, intestine, microbiota). Out of all the referred literature, ∼15% belonged to 2021-2023, ∼51% were from 2011-2020, and ∼32% from 2000-2010. ResultThe metabolic health benefits of green tea catechins are indeed influenced by the intestinal-level bioactivities, including reduction of mucosal inflammation and oxidative stress, attenuation of gut barrier dysfunction, decrease in intestinal lipid absorption and metabolism, favorable modulation of mucosal nuclear receptor signaling, alterations of the luminal global metabolome, and mitigation of the gut dysbiosis. The results from the recent clinical studies support the pre-clinical evidences. The challenges and pitfalls of the currently available knowledge on catechin bioactivities have been discussed, and constructive directions to harness the translational benefits of green tea through future interventions have been provided. ConclusionThe metabolism, metabolome, and microbiota at the intestinal epithelia play critical roles in catechin metabolism, pharmacokinetics, bioavailability, and bioactivities. Especially the reciprocal interaction between the catechins and the gut microbiota dictates the metabolic benefits of catechins.

Induction of mitophagy by green tea extracts and tea polyphenols: A potential anti-aging mechanism of tea

Tea consumption has been associated with anti-aging effects, however, the mechanisms involved are not well understood. Prompting mitochondrial health via the induction of mitophagy has recently been proposed as a novel anti-aging mechanism and the anti-aging properties of a few polyphenols including urolithin A have been linked to their abilities to induce mitophagy. Teas, rich in polyphenols, may also produce anti-aging effects through the induction of mitophagy. To test this hypothesis, a green tea extract and a few common tea polyphenols (catechins), were evaluated as potential mitophagy inducers in normal human fibroblasts. Mitophagy was detected by confocal microscopy and confirmed by Western blot analysis. A catechin-rich green tea extract (polyphenol content of 98%) induced mitophagy in normal human fibroblasts in a dose-dependent manner with a maximum effective concentration at ∼5 μg/mL, demonstrating comparable efficacy to urolithin A. Tea catechins also induced similar levels of mitophagy at an effective concentration of 5 μM for (-)-epicatechin gallate, EGCG and (-)-epicatechin, and 10 μM for (+)-catechin and (-)-epigallocatechin. These results demonstrate that the polyphenols in teas are powerful inducers of mitophagy in human fibroblast cells and induction of mitophagy may play an important role in the anti-aging mechanism of teas.

863-P: Effect of Bashan Tea Drink, a Vegetable Plant-Based Compound Tea Drink, on Blood Glucose in Type 2 Diabetic Patients

Background: The Bashan drink is a vegetable plant-based compound tea drink combing several pure plant ingredients. Plant-based ingredients are rich in phytochemicals, which can regulate human metabolic enzymes. For instance, catechin-rich green tea can reduce insulin resistance, increase insulin sensitivity and improve postprandial blood glucose. Objective: To observe the effects of Bashan on blood glucose (BG) in type 2 diabetes (T2DM) patients by a standardized mashed potato meal and continuous BG monitoring. Methods: A total of 29 patients (23 males, age 49.64±1.71years, HbA1c 8.49±0.42%) with T2DM who were newly diagnosed or failed to achieve glycemic control using antidiabetic monotherapy were included in the study. Subjects were randomized to take either 180ml of Bashan or water 3 times a day directly after meals for 2 weeks, with a 1-week washout period. Before and after the intervention, subjects were detected BG for 240 min after a mashed potato meal (368.5 kcal: 61.4 g carbohydrate, 7.4 g protein and 8.9 g fat). Average blood glucose(ABG) were collected from the continuous glucose monitors. Data are presented as means ± SEM, and P &amp;lt; 0.05 was considered statistically significant. Results: Four subjects were excluded for not completing the study. Compared with water, drinking Bashan significantly improved the ABG on day 10 to 12 (Bashan vs water: day 10, 7.37 ± 0.40 mmol/L vs 8.03 ± 0.45 mmol/L, P = 0.029; day 11, 7.17 ± 0.36 mmol/L vs 8.12 ± 0.59 mmol/L, P = 0.032; day 12, 6.90 ± 0.36 mmol/L vs 7.86 ± 0.54 mmol/L, P = 0.018). Drinking Bashan decreased HOMA2-IR and increased Homa2-%β, though not of statistical significance. (HOMA2-IR: Bashan day 14: 1.80 ± 0.17, day 1: 1.97 ± 0.19 vs water day 14: 1.83 ± 0.15, day 1: 1.80 ± 0.18, P &amp;gt;0.05; HOMA2-%β: Bashan day 14: 86.26±9.02, day 1: 73.40 ± 8.24 vs water day 14: 74.29 ± 7.46, day 1: 71.42 ± 7.27, P &amp;gt;0.05). Conclusion: Drinking Bashan continuously can improve ABG, and can potentially improve insulin resistance and β cell function. Disclosure C.Ni: None. Z.Sun: None. X.Zhou: None. S.Yao: None.

Catechin-Rich Green Tea Extract Reduced Intestinal Inflammation and Fasting Glucose in Metabolic Syndrome and Healthy Adults: A Randomized, Controlled, Crossover Trial

Abstract Objectives Preclinical evidence demonstrated that catechin-rich green tea extract (GTE) improves gut barrier function and reduces intestinal and systemic inflammation. Thus, this clinical trial was conducted to test the hypothesis that GTE would alleviate intestinal inflammation relative to cardiometabolic risk in persons with metabolic syndrome (MetS). Methods We conducted a randomized, double-blind, placebo-controlled, crossover trial in adults with MetS and age- and gender-matched healthy persons who received confections without (placebo) or with 1 g/d GTE (890 mg catechins) for 28 d while following a low-polyphenol diet. Dietary polyphenols, fasting blood glucose, insulin, and lipids were assessed at d 0, 14, and 28 of each intervention. Intestinal inflammation was assessed by measuring neutrophil-derived calprotectin and myeloperoxidase by ELISA in pooled stool samples collected over the last 3 d of each intervention. Data were analyzed using RM ANOVA and multiple linear regression. Results MetS (n = 21; 40 ± 3 y; 35 ± 1 kg/m2) and healthy (n = 19; 34 ± 2 y; 22 ± 0.4 kg/m2) persons completed the study with high compliance (&amp;gt;95%), no adverse effects, or changes in body mass. Participants’ total polyphenol intakes decreased during each intervention compared with baseline (P &amp;lt; 0.001). Fecal calprotectin and myeloperoxidase were lower (P &amp;lt; 0.05) in GTE compared with placebo regardless of health status. Although fasting insulin, triglycerides, total and high-density lipoprotein cholesterol were unaffected by treatment, fasting glucose decreased (P &amp;lt; 0.01) in response to GTE regardless of health status. Age (β = −0.29; P = 0.05) and between-trial changes in myeloperoxidase (β = 0.03; P &amp;lt; 0.04) were predictive of changes in insulin after controlling for sex, waist circumference, and changes in blood lipids and calprotectin. Conclusions Dietary intervention with GTE-rich confections in weight-stable healthy and MetS adults decreased fasting glucose and intestinal inflammation, which was associated with improvements in fasting insulin. This suggests that gut-level anti-inflammatory activities of GTE may improve glycemic control with reductions in intestinal inflammation contributing to enhance insulin sensitivity. Funding Sources USDA-NIFA, USDA-HATCH, and the Ohio Agricultural Research and Development Center at the Ohio State University.

A Green Tea Extract-Rich Confection in Healthy and Metabolic Syndrome Adults Decreases Small Intestinal Permeability in Association With Lower Gut Inflammation

ObjectivesPoor gut health, including increased intestinal permeability and inflammation, enhances cardiometabolic risk. Catechin-rich green tea extract (GTE) alleviates cardiometabolic complications in obese rodents by limiting gut permeability and inflammation, but whether these benefits occur in humans is not known. We hypothesized that the anti-inflammatory activities of GTE would decrease gut barrier dysfunction in persons at heightened cardiometabolic risk. MethodsIn a randomized, double-blind, placebo-controlled crossover study, persons with metabolic syndrome (MetS) and healthy persons completed two 4-wk interventions in which they received placebo or GTE confections (890 mg/d total catechins) while following a low-polyphenol diet. At wk 4, participants provided fecal samples for ELISA-based measures of inflammatory proteins. 24-h urine samples were also collected for LC/MS analysis of non-digestible sugars following the ingestion of lactulose (LAC), mannitol (MAN), sucralose (SUC), and erythritol (ERY). Data were analyzed by repeated measures ANOVA and linear regression controlling for within-subject repeated measures. ResultsMetS (n = 21; 40 ± 3 y; 35.2 ± 1.0 kg/m2) and healthy (n = 19; 34 ± 2 y; BMI = 22.3 ± 0.4 kg/m2) adults completed the study with no adverse effects, no changes in liver function tests, and > 95% compliance based on returned confections. Urinary SUC/ERY was unaffected by GTE and health status, but urinary LAC/MAN was lower (P = 0.043) in GTE compared with placebo regardless of health status. Fecal myeloperoxidase and calprotectin did not differ by health status, but were lower (P = 0.03–0.05) in response to GTE regardless of health status, and were positively correlated with each other (r = 0.75; P < 0.001). Fecal calprotectin and myeloperoxidase were both positively correlated with LAC/MAN ratio (r = 0.39–0.42; P = 0.01–0.02). ConclusionsInterim findings of this study support that dietary GTE decreases small intestinal permeability in association with lower gut inflammation, which may help to explain its known cardiometabolic benefits. Funding SourcesUSDA-NIFA (2019–67,017-29,259), USDA-HATCH, and the Ohio Agricultural Research and Development Center at The Ohio State University.

Prophylactic Catechin-Rich Green Tea Extract Treatment Ameliorates Pathogenic Enterotoxic Escherichia coli-Induced Colitis.

In this study, we explored the potential beneficial effects of green tea extract (GTE) in a pathogenic Escherichia coli (F18:LT:STa:Stx2e)-induced colitis model. The GTE was standardized with catechin and epigallocatechin-3-gallate content using chromatography analysis. Ten consecutive days of GTE (500 and 1000 mg/kg) oral administration was followed by 3 days of a pathogenic E. coli challenge (1 × 109 CFU/mL). In vitro antibacterial analysis showed that GTE successfully inhibited the growth of pathogenic E. coli, demonstrating over a 3-fold reduction under time- and concentration-dependent conditions. The in vivo antibacterial effect of GTE was confirmed, with an inhibition rate of approximately 90% when compared to that of the E. coli alone group. GTE treatment improved pathogenic E. coli-induced intestinal injury with well-preserved epithelial linings and villi. In addition, the increased expression of annexin A1 in GTE-treated jejunum tissue was detected, which was accompanied by suppressed inflammation-related signal expression, including TNFA, COX-2, and iNOS. Moreover, proliferation-related signals such as PCNA, CD44, and Ki-67 were enhanced in the GTE group compared to those in the E. coli alone group. Taken together, these results indicate that GTE has an antibacterial activity against pathogenic E. coli and ameliorates pathogenic E. coli-induced intestinal damage by modulating inflammation and epithelial cell proliferation.

Diet Therapeutics Interventions for Obesity: A Systematic Review and Network Meta-Analysis.

Background: Up to now, different diet therapeutics interventions have been introduced for the treatment of obesity. The present study aimed to compare the diet therapeutics interventions for obesity simultaneously. Study design: Systematic review and network meta-analysis Methods: The major international databases, including Medline (via PubMed), Web of Science, Scopus, Cochrane Library, and Embase, were searched using a predesigned search strategy. Randomized controlled trials (RCTs) that had compared the diet therapy interventions were included. The mean difference with a 95% confidence interval was used to summarize the effect size in the network meta-analysis. The frequentist approach was used for data analysis. Results: In total, 36 RCTs out of 9335 retrieved references met the inclusion criteria in this review. The included RCTs formed nine independent networks. Based on the results, Hypocaloricdiet+Monoselect Camellia (MonCam, P=0.99), energy restriction, behavior modification+exercise (LED) (P=0.99), sweetener at 20% of total calories (HFCS20)+Ex (P=0.67), catechin-richgreentea(650)+inulin (P=0.68), very low calorie diet (VLCD) (P=1.00), normal protein diet+resistance exercise (NPD+RT) (P=0.80), low-calorie diets+exercise (Hyc+Ex) (P=0.85), high-soy-protein low-fat diet (SD) (P=0.75), calorie restriction+behavioral weight loss (Hyc+BWL) (P=0.99) were the better treatments for weight loss in the networks one to nine, respectively. Conclusion: Based on the results of network meta-analysis, it seems that Hypocaloricdiet+MonCam, LED, HFCS20+Ex, catechin-rich green tea +inulin, VLCD, NPD+RT, Hyc+Ex, SD, Hyc+BWL, are the better treatments for weight loss in patients with overweight and obesity.

Diet Therapeutics Interventions for Obesity: A Systematic Review and Network Meta-Analysis

Background: Up to now, different diet therapeutics interventions have been introduced for the treatment of obesity. The present study aimed to compare the diet therapeutics interventions for obesity simultaneously. Study design: Systematic review and network meta-analysis Methods: The major international databases, including Medline (via PubMed), Web of Science, Scopus, Cochrane Library, and Embase, were searched using a predesigned search strategy. Randomized controlled trials (RCTs) that had compared the diet therapy interventions were included. The mean difference with a 95% confidence interval was used to summarize the effect size in the network meta-analysis. The frequentist approach was used for data analysis. Results : In total, 36 RCTs out of 9335 retrieved references met the inclusion criteria in this review. The included RCTs formed nine independent networks. Based on the results, Hypocaloricdiet+Monoselect Camellia (MonCam, P=0.99), energy restriction, behavior modification+exercise (LED) (P=0.99), sweetener at 20% of total calories (HFCS20)+Ex (P=0.67), catechin-richgreentea(650)+inulin (P=0.68), very low calorie diet (VLCD) (P=1.00), normal protein diet+resistance exercise (NPD+RT) (P=0.80), low-calorie diets+exercise (Hyc+Ex) (P=0.85), high-soy-protein low-fat diet (SD) (P=0.75), calorie restriction+behavioral weight loss (Hyc+BWL) (P=0.99) were the better treatments for weight loss in the networks one to nine, respectively. Conclusion: Based on the results of network meta-analysis, it seems that Hypocaloricdiet+MonCam, LED, HFCS20+Ex, catechin-rich green tea +inulin, VLCD, NPD+RT, Hyc+Ex, SD, Hyc+BWL, are the better treatments for weight loss in patients with overweight and obesity.

Effect of whole green tea products including catechins, polysaccharides, and flavonols on the metabolism of added sugars

The current study was investigated the effect of catechin rich green tea extracts (GTE) formulated with excipient components, crude tea polysaccharides (CTP), and flavonols (FVN) derived from green tea on sucrose hydrolysis and intestinal transport of monosaccharides using an in vitro digestion system with Caco-2 cell. Sucrose (10 mg) co-digested with GTE (1 mg) + FVN (0.01 mg) or GTE (1 mg) + CTP (0.1 mg) + FVN (0.01 mg) was less hydrolyzed into glucose and fructose, which showed 90.4 ± 1.36% and 91.75 ± 1.48% for the control (sucrose), respectively. Approximately 65.59% of the glucose released from the sucrose digested with GTE (1 mg) + CTP (0.1 mg) + FVN (0.01 mg) was subsequently transported by Caco-2 cell, which was significantly lower than other treatments (p < 0.05). The intestinal transport of fructose was inhibited by the co-digestion with GTE (1 mg) + FVN (0.01 mg) (43.65% of control) and GTE (1 mg) + CTP (0.1 mg) + FVN (0.01 mg) (43.12% of control). When glucose or fructose was directly treated to Caco-2 cell, glucose transport was inhibited in GTE (60.7% of control), while fructose transport was repressed in GTE + CTP + FVN (54.75% of control). Epithelial permeability (%) of the glucose and fructose ranged from 14.77 to 24.33% and 1.5–2.24%, respectively. Results suggest that co-intake catechin rich extract of catechin rich extract with polysaccharides and flavonols derived from green tea processing could be potential hypoglycemic ingredients when added sugars are consumed.

Acute effect of green tea catechins on uric acid metabolism after alcohol ingestion in Japanese men

Alcohol consumption is associated with hyperuricemia and gout. Previous studies have indicated a role for green tea catechins in uric acid (UA) metabolism. This study aimed to elucidate the acute effect of green tea catechins in terms of enhancing urinary excretion of UA and xanthine/hypoxanthine (Xa/HX; UA precursors) after alcohol ingestion. In a randomized crossover study, ten healthy Japanese subjects consumed test meals, including a Japanese distilled spirit (Shōchū) with water (SW) or Shōchū with catechin-rich green tea (SC), each containing 20 g of alcohol. The SC contained 617 mg of catechin in total. Serum and urine UA and Xa/HX concentrations were measured. Blood samples were collected after 2.5 h, and urine samples were collected between 0 and 5 h after consuming the test meal. Urine UA and Xa/HX excretions were significantly higher in the SC group than in the SW group (UA: SW, 0.45 ± 0.08; SC, 0.52 ± 0.09; Xa/HX: SW, 0.08 ± 0.04; SC, 0.16 ± 0.05 mg/kg/h). UA clearance (CUA) and fractional UA excretion (FEUA) tended to increase more in the SC group than in the SW group (CUA: SW, 7.76 ± 2.14; SC, 8.75 ± 2.23 mL/min/1.73 m2; FEUA: SW, 6.08 ± 1.36; SC, 6.64 ± 1.42%). No significant differences in serum UA and Xa/HX concentrations were observed between two groups. It was concluded that green tea catechins can enhance the excretion of UA and Xa/HX, even though alcohol is ingested. UMIN000040076. Retrospectively registered 7 April 2020. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000045687 Key Points • Green tea catechins enhance the excretion of uric acid and xanthine/hypoxanthine, even when alcohol is ingested simultaneously. • In case of non-adherence of limiting alcohol intake, catechin-rich green tea may be an effective dietary component to continue dietary therapy.

Catechin-Rich Green Tea Extract and the Loss-of-TLR4 Signaling Differentially Alter the Hepatic Metabolome in Mice with Nonalcoholic Steatohepatitis.

Catechin-rich green tea extract (GTE) limits inflammation in nonalcoholic steatohepatitis (NASH) consistent with a Toll-like receptor 4 (TLR4)-dependent mechanism. It is hypothesized that GTE supplementation during NASH will shift the hepatic metabolome similar to that attributed to the loss-of-TLR4 signaling. Wild-type (WT) and loss-of-function TLR4-mutant (TLR4mut ) mice are fed a high-fat diet containing 0% or 2% GTE for 8 weeks prior to performing untargeted mass spectrometry-based metabolomics on liver tissue. The loss-of-TLR4 signaling and GTE shift the hepatic metabolome away from that of WT mice. However, relatively few metabolites are altered by GTE in WT mice to the same extent as the loss-of-TLR4 signaling in TLR4mut mice. GTE increases acetyl-coenzyme A precursors and spermidine to a greater extent than the loss-of-TLR4 signaling. Select metabolites associated with thiol metabolism are similarly affected by GTE and the loss-of-TLR4 signaling. Glycerophospholipid catabolites are decreased by GTE, but are unaffected in TLR4mut mice. Conversely, the loss-of-TLR4 signaling but not GTE increases several bile acid metabolites. GTE limitedly alters the hepatic metabolome consistent with a TLR4-dependent mechanism. This suggests that the anti-inflammatory activities of GTE and loss-of-TLR4 signaling that regulate hepatic metabolism to abrogate NASH are likely due to distinct mechanisms.

Enhancing the effect of catechins with green tea flavonol and polysaccharides on preventing lipid absorption and accumulation

The hypothesis of the current study was that flavonol and polysaccharides obtained during catechins extraction from green tea may enhance the effect of catechins on preventing pancreatic lipase activity, free glycerol absorption and accumulation in adipocytes co-cultured with Caco-2 cell after in vitro digestion. Catechins rich extract from green tea (GCT: 10 mg), GCT formulated with polysaccharides (GTP: 1 mg) and flavonol extract (GFV: 0.1 mg) strongly inhibited lipase activity during digestion while increasing lipolysis in adipocytes. Lipid accumulation in adipocytes was significantly reduced in GCT (10 mg) + GTP (1 mg) + GFV (1 mg) (100–87.27%) compared to control (p < 0.05). When targeted single flavonols (myricetin, quercetin, and kaempferol) were added into catechins in GCT (EGCG), the lipid accumulation in adipocyte ranged from 82.07 to 89.11% of control. EGCG (3 mg) + Quercetin (0.3 mg) transported the lowest amount of glycerol (2.18 ± 0.18 mM) in aqueous fraction from the digesta to the Caco-2 cell. Results from the current study suggested that co-consumption of catechin rich green tea extracts with by-products including flavonols and polysaccharides obtained during green tea processing could be potential natural components on anti-obesity by preventing lipid intestinal absorption and accumulation in adipocytes.

Epigallocatechin gallate but not catechin prevents nonalcoholic steatohepatitis in mice similar to green tea extract while differentially affecting the gut microbiota

Catechin-rich green tea extract (GTE) protects against nonalcoholic steatohepatitis (NASH) by alleviating gut-derived endotoxin translocation and hepatic Toll-like receptor-4 (TLR4)–nuclear factor κB (NFκB) inflammation. We hypothesized that intact GTE would attenuate NASH-associated responses along the gut–liver axis to a greater extent than purified (−)-epigallocatechin gallate (EGCG) or (+)-catechin (CAT). Male C57BL/6J mice were fed a low-fat diet, a high-fat (HF) diet, or the HF diet with 2% GTE, 0.3% EGCG or 0.3% CAT for 8 weeks prior to assessing NASH relative to endotoxemia, hepatic and intestinal inflammation, intestinal tight junction proteins (TJPs) and gut microbial ecology. GTE prevented HF-induced obesity to a greater extent than EGCG and CAT, whereas GTE and EGCG more favorably attenuated insulin resistance. GTE, EGCG and CAT similarly attenuated serum alanine aminotransferase and serum endotoxin, but only GTE and EGCG fully alleviated HF-induced NASH. However, hepatic TLR4/NFκB inflammatory responses that were otherwise increased in HF mice were similarly attenuated by GTE, EGCG and CAT. Each treatment also similarly prevented the HF-induced loss in expression of intestinal TJPs and hypoxia inducible factor-1α and the otherwise increased levels of ileal and colonic TNFα mRNA and fecal calprotectin protein concentrations. Gut microbial diversity that was otherwise lowered in HF mice was maintained by GTE and CAT only. Further, microbial metabolic functions were more similar between GTE and CAT. Collectively, GTE catechins similarly protect against endotoxin–TLR4–NFκB inflammation in NASH, but EGCG and CAT exert differential prebiotic and antimicrobial activities suggesting that catechin-mediated shifts in microbiota composition are not entirely responsible for their benefits along the gut–liver axis.

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.

A Randomized Placebo-controlled, Double-blind Study of Kosen-cha, a Polymerized Catechin-rich Green Tea, for Obesity in Pre-obese Japanese Subjects

A Randomized Placebo-controlled, Double-blind Study of Kosen-cha, a Polymerized Catechin-rich Green Tea, for Obesity in Pre-obese Japanese Subjects

Intestinal-level anti-inflammatory bioactivities of catechin-rich green tea: Rationale, design, and methods of a double-blind, randomized, placebo-controlled crossover trial in metabolic syndrome and healthy adults

Metabolic endotoxemia initiates low-grade chronic inflammation in metabolic syndrome (MetS) and provokes the progression towards more advanced cardiometabolic disorders. Our recent works in obese rodent models demonstrate that catechin-rich green tea extract (GTE) improves gut barrier integrity to alleviate the translocation of gut-derived endotoxin and its consequent pro-inflammatory responses mediated through Toll-like receptor-4/nuclear factor κB (TLR4/NFκB) signaling. The objective of this clinical trial is to establish the efficacy of GTE to alleviate metabolic endotoxemia-associated inflammation in persons with MetS by improving gut barrier function. We plan a double-blind, placebo-controlled cross-over trial in persons with MetS and age- and gender-matched healthy persons (18–65 y; n = 20/group) who will receive a low-energy GTE-rich (1 g/day; 890 mg total catechins) confection snack food while following a low-polyphenol diet for 28 days. Assessments will include measures of circulating endotoxin (primary outcome) and secondary outcomes including biomarkers of endotoxin exposure, region-specific measures of intestinal permeability, gut microbiota composition, diversity, and functions, intestinal and systemic inflammatory responses, and catechins and microbiota-derived catechin metabolites. Study outcomes will provide the first report of the GTE-mediated benefits that alleviate gut barrier dysfunction in relation to endotoxemia-associated inflammation in MetS persons. This is expected to help establish an effective dietary strategy to mitigate the growing burden of MetS that currently affects ~35% of Americans.

Green Tea Extract Treatment in Obese Mice with Nonalcoholic Steatohepatitis Restores the Hepatic Metabolome in Association with Limiting Endotoxemia-TLR4-NFκB-Mediated Inflammation.

Catechin-rich green tea extract (GTE) alleviates nonalcoholic steatohepatitis (NASH) by lowering endotoxin-TLR4 (Toll-like receptor-4)-NFκB (nuclear factor kappa-B) inflammation. This study aimed to define altered MS-metabolomic responses during high-fat (HF)-induced NASH that are restored by GTE utilizing livers from an earlier study in which GTE decreased endotoxin-TLR4-NFκB liver injury. Mice are fed a low-fat (LF) or HF diet for 12 weeks and then randomized to LF or HF diets containing 0% or 2% GTE for an additional 8 weeks. Global MS-based metabolomics and targeted metabolite profiling of catechins/catechin metabolites are evaluated. GTE in HF mice restores hepatic metabolites implicated in dyslipidemia insulin resistance, and inflammation. These include 122 metabolites: amino acids, lipids, nucleotides, vitamins, bile acids, flavonoids, xenobiotics, and carbohydrates. Hepatic amino acids, B-vitamins, and bile acids are inversely correlated with biomarkers of insulin resistance, liver injury, steatosis, and inflammation. Further, phosphatidylcholine metabolites are positively correlated with biomarkers of liver injury and NFκB inflammation. Thirteen catechin metabolites are identified in livers of GTE-treated mice, mostly as phase II conjugates of parental catechins or microbial-derived valerolactones. The defined anti-inflammatory/metabolic interactions advance an understanding of the mechanism by which GTE catechins protect against NFκB-mediated liver injury in NASH.

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.

Green Tea Extract (Camellia sinensis) as a Potential Antitumoral Agent on Breast Cancer Cells (FS13-04-19)

ObjectivesWe aimed to obtain a catechin-rich green tea extract (GTE) from Camellia sinensis and to evaluate its antitumor potential on human breast cancer. Green tea (GT) has been extensively studied for its antioxidant property, which is mainly attributed to catechins. These phenolic compounds regulate many cellular targets involved in cancer signaling pathways, including those mediated by p53 tumor suppressor protein. MethodsTea infusion was prepared on a ratio of 1 g:40 mL of boiling distilled water using a combination of temperature and time (70, 75, 80, 85, 90, 95 and 100 °C/5, 10, 15 min). Infusions were evaluated by polyphenols content (Folin–Ciocalteu’s reagent) and antioxidant potential (FRAP). Breast cancer cells (MDA-MB-231 and MCF-7) and non-tumoral cells (MCF-10A), were exposed to different concentrations of GTE (31.5 μg/mL to 1.0 mg/mL) during 24 h-48 h, and cell viability was assessed by Alamar Blue® and Trypan Blue assays. Viability was also acessed in the presence of a p53 protein inibitor, pifithrin-α. Immunocytochemistry and Western blotting analysis were performed to access the expression of p53. ResultsOur results demonstrated no influence of extraction condition in the total content of polyphenols and antioxidant potential of GT, and a new extract was obtained at 80 °C/5 min, then freeze dried to be used in cell culture. After exposure for 24 h, GTE already promoted a cytotoxic effect, reducing viability of both breast cancer cell lines (IC50 MDA-MB-231 = 138,8 μg/mL; IC50 MCF-7 = 324,5 μg/mL) without cytotoxic effect on non-tumoral cells (IC50 MCF-10A = 10,097 μg/mL). In addition, GTE promotes an increase of p53 levels on treated MCF-7 cells, which express the wild-type form of the protein. Interestingly, an opposite phenomenon was evidenced in MDA-MB-231 cells, that express the mutated form of p53, in which protein levels seem to be lower in the presence of the extract. ConclusionsOur data suggests that GTE has anticarcinogenic potential on breast cancer and it is possible that this capacity might be related with the modulation of p53 tumor suppressor protein. Funding SourcesFAPERJ, FUNDAÇÃO DO CÂNCER, CAPES, CNPq.