This study evaluated the effect of green tea extract and metformin and its interaction on markers of oxidative stress and inflammation in overweight women with insulin resistance. After screening, 120 women were randomly allocated in 4 groups: Placebo (PC): 1g of microcrystalline cellulose/day; Green tea (GT): 1 g (558 mg polyphenols) of standardized dry extract of green tea/day and 1 g of placebo/day; Metformin (MF): 1 g of metformin/day and 1 g of placebo/day; Green Tea and Metformin (GTMF): 1 g (558 mg polyphenols) and 1 g of metformin/day. All groups were followed-up for 12 weeks with assessment of oxidative damage to lipids and proteins, specific activity of antioxidant enzymes and inflammatory cytokine serum levels. The association of green tea with metformin significantly reduced IL-6 (GTMF: –29.7((–62.6)–20.2))(p = 0.004). Green tea and metformin isolated reduced TNF-α (GT: –12.1((–18.0)–(–3.5)); MF: –24.5((–38.60)–(–4.4)) compared to placebo (PB: 13.8 (1.2–29.2))(P < 0.001). Also, isolated metformin reduced TGF-β (MF: –25.1((–64.4)–0.04)) in comparison to placebo (PB: 6.3((–1.0)–16.3))(p = 0.038). However, when combined, their effects were nullified either for TNF-α (GTMF: 6.0((–5.7)–23.9) and for TGF-β (GTMF: –1.8((–32.1)–8.5). This study showed that there is a drug-nutrient interaction between green tea and metformin that is dependent on the cytokine analyzed.

The literature on green tea consumption and glucose metabolism has reported conflicting findings. This cross-sectional study examined the association of green tea consumption with abnormal glucose metabolism among 3000 rural residents aged 40–60 years in Khánh Hòa province in Vietnam. Multinomial logistic regression analysis was conducted to examine the association of green tea consumption (0, < 200, 200–< 400, 400–< 600 or ≥ 600 ml/d) with prediabetes and diabetes (based on the American Diabetes Association criteria). Linear regression analysis was performed to examine the association between green tea consumption and the log-transformed homeostatic model assessment of insulin resistance (HOMA-IR) (a marker of insulin resistance) and the log-transformed homeostatic model assessment of β-cell function (HOMA-β) (a marker of insulin secretion). The OR for prediabetes and diabetes among participants who consumed ≥ 600 ml/d v. those who did not consume green tea were 1·61 (95 % CI = 1·07, 2·42) and 2·04 (95 % CI = 1·07, 3·89), respectively. Higher green tea consumption was associated with a higher level of log-transformed HOMA-IR (Pfor trend = 0·04) but not with a lower level of log-transformed HOMA-β (Pfor trend = 0·75). Higher green tea consumption was positively associated with the prevalence of prediabetes, diabetes and insulin resistance in rural Vietnam. The findings of this study indicated prompting the need for further research considering context in understanding the link between green tea consumption and glucose metabolism, especially in rural settings in low- and middle-income countries.

The aim of the present study was to examine the effects of green tea epigallocatechin-3-gallate (EGCG) on changes in body composition, energy and substrate metabolism, cardiometabolic risk factors and liver function enzymes after an energy-restricted diet intervention in obese women. In the present randomised, double-blind, placebo-controlled study, eighty-three obese (30 kg/m2>BMI < 40 kg/m2) pre-menopausal women consumed 300 mg/d of EGCG or placebo (lactose). We measured body weight and adiposity (dual-energy X-ray absorptiometry), energy expenditure and fat oxidation rates (indirect calorimetry), blood lipid levels (TAG, total cholesterol, LDL-cholesterol and HDL-cholesterol), insulin resistance, C-reactive protein and liver function markers (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, γ-glutamyltransferase, urea, bilirubin and 2-keto[1-13C]isocaproate oxidation) before and after the intervention in the EGCG and control groups. We did not find any significant difference in the changes in body weight ( − 0·3 kg, 95 % CI − 5·0, 4·3), fat mass ( − 0·7 kg, 95 % CI − 3·5, 2·1), energy (0·3 kJ/kg per d, 95 % CI − 3·1, 2·7) and fat ( − 0·1 g/min, 95 % CI − 0·03, 0·01) metabolism, homeostasis assessment model for insulin resistance (0·2, 95 % CI − 0·2, 0·7), total cholesterol ( − 0·21 mmol/l, 95 % CI − 0·55, 0·13), LDL-cholesterol ( − 0·15 mmol/l, 95 % CI − 0·50, 0·20), TAG ( − 0·14 mmol/l, 95 % CI − 0·56, 0·29) and liver function markers between the EGCG and control groups. In conclusion, the present results suggest that dietary supplementation with 300 mg/d of EGCG for 12 weeks did not enhance energy-restricted diet-induced adiposity reductions, and did not improve weight-loss-induced changes in cardiometabolic risk factors in obese Caucasian women. The intake of 300 mg/d of EGCG for 12 weeks did not cause any adverse effect on liver function biomarkers.

Green tea (Camellia sinensis) catechin profiles in plasma and urine following single dosing and regular ingestion of green tea are not clear. We performed a placebo-controlled intervention study with sixteen healthy volunteers to determine changes in total and free catechins after a single dose and following 1 week of twice-daily green tea. Blood and urine samples were collected before (fasting) and after (60 and 120 min for blood; 90 and 180 min for urine) drinking 200 ml of 1·5 % (w/v) green tea or water (n 8 each), and fasting samples were again collected after 7 d of 150 ml of 1 % (w/v) supplemental green tea or water twice daily. After a 4-week washout, subjects were crossed onto the other treatment and procedures repeated. Plasma results at 1 h post-ingestion showed elevated (P< 0·05) mean epigallocatechin gallate (EGCG; 310 (sd 117) nmol/l; all in free form), epigallocatechin (EGC; 192 (sd 67) nmol/l; 30 % free) and epicatechin gallate (ECG; 134 (sd 51) nmol/l; 75 % free). Fasting plasma after 7 d of regular intake showed increased (P< 0·05) EGCG (80 v. 15 nmol/l at baseline) and ECG (120 v. 40 nmol/l), with ≥ 90 % of both in their conjugated forms. Total EGC was < 10 nmol/l. Post-ingestion conjugation and renal loss of EGC and epicatechin were rapid and high, but were negligible for EGCG and ECG. In the green tea consumed, the content was EGCG >EGC >ECG, and the acute plasma response mirrored this. However, after chronic consumption there was almost no EGC found in fasting plasma, some EGCG was present, but a rather high level of ECG was maintained.

Green tea catechin has been proposed to have an anti-obesity effect. The aim of the present study was to investigate whether the effect of catechin-rich green tea in combination with inulin affects body weight and fat mass in obese and overweight adults. A total of thirty subjects were divided into a control group and an experimental group who received 650 ml tea or catechin-rich green tea plus inulin. A reduction of body weight ( − 1·29 (sem 0·35) kg) and fat mass (0·82 (sem 0·27) kg) in the experimental group was found after 6 weeks, and no adverse effects were observed. After refraining from consumption for 2 weeks, sustained effects on body weight and fat mass were observed. We conclude that continuous intake of catechin-rich green tea in combination with inulin for at least 3 weeks may be beneficial for weight management.

The increase in the prevalence of obesity in recent years has prompted research into alternative methods of modulating body weight and body fat. The last decade has reflected this with a surge in studies investigating the potential of green tea as a natural agent of weight loss, with a view to confirming and elucidating the mechanisms underlying its effect on the body. Currently, it is widely believed that the polyphenolic components present in green tea have an anti-obesogenic effect on fat homeostasis, by increasing thermogenesis or reducing fat absorption among other ways. The data published to date, however, are inconsistent, with numerous putative modes of action suggested therein. While several unimodal mechanisms have been postulated, a more plausible explanation of the observed results might involve a multimodal approach. Such a mechanism is suggested here, involving simultaneous inhibition of the enzymes catechol-O-methyltransferase, acetyl-CoA carboxylase, fatty acid synthase and impeding absorption of fat via the gut. An evaluation of the available evidence supports a role of green tea in weight loss; however the extent of the effects obtained is still subject to debate, and requires more objective quantification in future research.

The beneficial effects of green tea catechins, such as the proposed improvement in endothelial function, may be influenced by phase II metabolism during and after absorption. The methylation enzyme, catechol-O-methyltransferase (COMT), has a missense mutation rs4680 (G to A), proposed to result in a 40 % reduction in enzyme activity. In the present pilot study, twenty subjects (ten of each homozygous COMT genotype) were recruited. Green tea extract capsules (836 mg green tea catechins) were given in a fasted state, and a high-carbohydrate breakfast was given after 60 min. Blood samples and vascular function measurements were taken at regular intervals. The change in digital volume pulse stiffness index (SI) from baseline was shown to be different between genotype groups at 120 and 240 min, with a lower SI in the GG individuals (P ≤ 0·044). The change in blood pressure from baseline also differed between genotype groups, with a greater increase in systolic (P = 0·023) and diastolic (P = 0·034) blood pressure at 120 min in the GG group. The AA group was shown to have a greater increase in insulin concentrations at 120 min (P = 0·019) and 180 min (P = 0·008) compared with baseline, despite similar glucose profiles. No genotypic differences were found in vascular reactivity measured using laser Doppler iontophoresis, total nitrite, lipids, plasma total antioxidant capacity or inflammatory markers after ingestion of the green tea extract. In conclusion, SI and insulin response to the glucose load differed between the COMT genotype groups, and this may be suggestive of a green tea extract and genotype interaction.

Green tea is rich in polyphenolic antioxidants and has widely reported but largely unsubstantiated health benefits. In the present study, genoprotective effects of two types of green tea were studied both in an in vitro and in a human supplementation trial. For the in vitro study, human lymphocytes were pre-incubated in tea (0·005–0·1 %, w/v), washed and subjected to oxidant challenge induced by H2O2. In a placebo-controlled, cross-over supplementation study, eighteen healthy volunteers took 2 × 150 ml/d of 1 % (w/v) green tea (‘Longjing’ green tea or ‘screw-shaped’ green tea) or water (control) for 4 weeks (n 6). Subjects took all the three treatments in a random order, with 6 weeks' washout between each treatment. Fasting blood and urine were collected before and after each treatment. The comet assay was used to measure the resistance of lymphocytic DNA to H2O2-induced challenge. Basal oxidation-induced DNA damage was measured using the formamidopyrimidine glycosylase (Fpg) enzyme-assisted comet assay. Urine 7,8-dihydro-2-deoxyguanosine (8-oxodG, mol/mmol creatinine), a biomarker of whole-body oxidative stress, was measured by liquid chromatography with tandem MS. In vitro testing results of tea-treated cells showed increased (P < 0·05) resistance of DNA to the challenge. In the supplementation trial, a significant (P < 0·05) increase in resistance was also observed. Furthermore, the FPg comet data showed >20 % decrease in DNA damage with tea supplementation: mean and standard deviation changes in %DNA in comet tail in the Fpg-assisted comet assay were: − 5·96 (sd 3·83) % after Longjing tea; − 6·22 (sd 3·34) % after screw-shaped tea; +0·91 (sd 5·79) % after water (P < 0·05). No significant changes in urine 8-oxodG were seen. The results indicate that green tea has significant genoprotective effects and provide evidence for green tea as a ‘functional food’.

Coffee and green tea are two of the most widely consumed hot beverages in the world. Their respective bioavailability has been studied separately, but absorption of their respective bioactive phenolics has not been compared. In a randomised cross-over design, nine healthy subjects drank instant coffee and green tea. Blood samples were collected over 12 h and at 24 h to assess return to baseline. After green tea consumption, ( − )-epigallocatechin (EGC) was the major catechin, appearing rapidly in the plasma; ( − )-EGC gallate (EGCg) and ( − )-epicatechin (EC) were also present, but ( − )-EC gallate and C were not detected. Dihydroferulic acid and dihydrocaffeic acid were the major metabolites that appeared after coffee consumption with a long time needed to reach maximum plasma concentration, suggesting metabolism and absorption in the colon. Other phenolic acid equivalents (caffeic acid (CA), ferulic acid (FA) and isoferulic acid (iFA)) were detected earlier, and they peaked at lower concentrations. Summations of the plasma area under the curves (AUC) for the measured metabolites showed 1·7-fold more coffee-derived phenolic acids than green tea-derived catechins (P = 0·0014). Furthermore, we found a significant correlation between coffee metabolites based on AUC. Inter-individual differences were observed, but individuals with a high level of CA also showed a correspondingly high level of FA. However, no such correlation was observed between the tea catechins and coffee phenolic acids. Correlation between AUC and maximum plasma concentration was also significant for CA, FA and iFA and for EGCg. This implies that the mechanisms of absorption for these two classes of compounds are different, and that a high absorber of phenolic acids is not necessarily a high absorber of catechins.

Obesity predisposes to an increased incidence of diabetes and CVD. Also, obesity is a pro-inflammatory state. Regulatory T cells (Tregs) are essential negative regulators of inflammation and are down-regulated in pro-inflammatory states. Animal models of obesity are associated with decreased Tregs. The dietary modulation of Tregs could be used as a therapeutic strategy to control inflammation. Epigallocatechin gallate (EGCG) is a potent anti-inflammatory agent and an active ingredient of green tea and is suggested to have a role as a preventive agent in obesity, diabetes and CVD. The role of EGCG in the modulation of Tregs has, however, not been studied. Thus, the aim of the present study was to determine the effect of EGCG on the number and function of Tregs in obese and lean human subjects in vitro, and to delineate its specific regulation mechanisms. Tregs were isolated from normal-weight and obese subjects. Tregs were cultured in the absence or presence of EGCG (20 μm) for 24 h. Foxp3-expressing Tregs were enumerated using flow cytometry. Histone deacetylase (HDAC) activity and nuclear NF-κBp65 level were measured by ELISA and Western blots. Obese subjects had lower Tregs and IL-10 production than lean subjects. EGCG treatment significantly enhanced the number of Foxp3-expressing Tregs and IL-10 production in vitro (P < 0·05) in both groups. Also, EGCG decreased NF-κB activity and increased HDAC activity and HDAC-2 expression in Tregs (P < 0·05) in both groups. Thus, in part, EGCG enhances the functionality of Tregs, i.e. IL-10 production and number by suppressing the NF-κB signalling pathway via inducing epigenetic changes.

The health benefits of green tea (Camellia sinensis) catechins are becoming increasingly recognised. Amongst the proposed benefits are the maintenance of endothelial function and vascular homeostasis and an associated reduction in atherogenesis and CVD risk. The mounting evidence for the influential effect of green tea catechins on vascular function from epidemiological, human intervention and animal studies is subject to review together with exploration of the potential mechanistic pathways involved. Epigallocatechin-3-gallate, one of the most abundant and widely studied catechin found in green tea, will be prominent in the present review. Since there is a substantial inconsistency in the published data with regards to the impact of green tea catechins on vascular function, evaluation and interpretation of the inter- and intra-study variability is included. In conclusion, a positive effect of green tea catechins on vascular function is becoming apparent. Further studies in animal and cell models using physiological concentrations of catechins and their metabolites are warranted in order to gain some insight into the physiology and molecular basis of the observed beneficial effects.

Hypoxia/reoxygenation is one of the causes of the increased expression of inducible NO synthase in cardiomyocytes. In a recent study we demonstrated that a single, high dose of green tea extract (GT) supplemented to the medium of cultured cardiomyocytes just before hypoxia/reoxygenation is able to prevent the increased expression of inducible NO synthase, therefore reducing NO overproduction. In the present study we investigated the mechanism by which GT reduces NO production. Since a molecular mechanism for polyphenol activity has been postulated, and PPAR activation is related to the transcription of the inducible NO synthase gene, we evaluated the activation of PPAR by GT. A moderate GT concentration, supplemented to the cardiomyocyte medium since the initial seeding, selectively activated the PPAR-β/δ isoform. Furthermore, we observed a reduction in NO production and an increase in total antioxidant activity, indicating that GT components may act on both reactive oxygen species, via an antioxidant mechanism, and NO overproduction. PPAR-β/δ activation could represent the key event in the reduction of NO production by GT. Although PPAR activation by GT was lower than activation by fenofibrate, it is very interesting to note that it was selective for the β/δ isoform, at least in neonatal cardiomyocytes.

As in man, canine obesity is associated with insulin resistance, dyslipidaemia and other chronic diseases. This study was designed to examine the effects of a nutritional supplement (green tea) on insulin sensitivity and plasma lipid concentrations in an obese insulin-resistant dog model. We also determined mRNA expression of two transcription factors, PPARγ and PPARα, and some of their target genes, including GLUT4, lipoprotein lipase (LPL) and adiponectin. Obese dogs were divided into two groups: a green tea group (n 6); a control group (n 4). Dogs in the green tea group were given green tea extract (80 mg/kg per d) orally, just before their single daily meal, for 12 weeks. Insulin sensitivity (using a euglycaemic–hyperinsulinaemic clamp) and concentrations of plasma TAG, total cholesterol and NEFA were assessed in each group. Gene expression was measured in visceral and subcutaneous adipose tissues and in liver and skeletal muscle, by real-time PCR. At 12 weeks in the green tea group, mean insulin sensitivity index was 60 (sem 11) % higher (P < 0·05) and TAG concentration 50 (sem 10) % lower (P < 0·001), than baseline. PPARγ, GLUT4, LPL and adiponectin expression were significantly higher in both adipose tissues, whilst PPARα and LPL expression were significantly higher in skeletal muscle, compared with baseline. These findings show that nutritional doses of green tea extract may improve insulin sensitivity and lipid profile and alter the expression of genes involved in glucose and lipid homeostasis.

It has been documented that green tea (GT) and its catechin components improve renal failure and inhibit the growth of mesangial cells. In the present study we examined the long-term effect of GT extract on streptozotocin (STZ)-induced diabetic nephropathy and on the glycogen accumulation in the kidney tubules. Male Sprague–Dawley rats were randomly assigned to normal control groups (2, 6, 8 and 12 weeks) and five diabetic groups (n 10) of comparable age. A GT diabetic group received 16 % concentration of GT for 12 weeks post-diabetes induction as their sole source of drinking water. GT treatment significantly (P < 0·01) reduced the serum glucose, glycosylated protein, serum creatinine and blood urea N levels by 29·6 (sem 3·7), 22·7 (sem 5·2), 38·9 (sem 10) and 41·7 (sem 1·9) %, respectively, compared with the diabetic group of comparable age. In addition, the GT-treated group showed a significant 44 (sem 10·8) % higher creatinine clearance (Ccr) compared with the untreated diabetic group. Likewise, GT reduced the urea N, creatinine, glucose and protein excretion rates by 30 (sem 7·6), 35·4 (sem 5·3), 34·0 (sem 5·3) and 46·0 (sem 13·0) % compared with the 12 weeks diabetic group. Administration of GT to 12 weeks diabetic rats significantly (P < 0·001) prevented (99·98 (sem 0·27) % less) the accumulation of glycogen in the kidney tubules. These results indicate that in STZ diabetes, kidney function appears to be improved with GT consumption which also prevents glycogen accumulation in the renal tubules, probably by lowering blood levels of glucose. Therefore, GT could be beneficial additional therapy in the management of diabetic nephropathy.

Interest in functional foods is increasing. The aim of the present study was to investigate breads supplemented with functional components. One was bread supplemented with inulin, linseed and soya fibre (prebiotic bread). The other was a prebiotic antioxidant bread (pre-aox-bread), which additionally contained green tea powder, herbs and tomato paste. The effects of these two breads on immunological and antioxidative parameters were compared with control bread (placebo). Twenty smokers and eighteen non-smokers were enrolled in the randomised parallel study, which consisted of a control period and an intervention period, each lasting for 5 weeks. Daily intake of bread and nutrients did not differ between the intervention and the control period. Most of the twenty-three investigated immunological parameters measured in peripheral blood were unaffected. However, the percentage of CD19 increased after intervention with prebiotic bread, whereas intercellular adhesion molecule-1 (ICAM-1) and CD3+NK+ (P < 0·05) decreased in both intervention arms. The ferric reducing ability of plasma (FRAP) was increased after consumption of the pre-aox-bread for non-smokers (1256 v. 1147 μmol/l; P = 0·019) and remained unchanged for smokers consuming the pre-aox-bread. All analysed carotenoids (P ≤ 0·001) in plasma were increased after the consumption of pre-aox-bread. The concentrations of uric acid and α-tocopherol rose after intervention with both breads. ICAM-1 as a marker of stress decreased after consuming the prebiotic bread. In conclusion, increased plasma concentrations of carotenoids and the responses observed with the FRAP assay after intervention with the pre-aox-bread indicate a unique response in terms of antioxidative potentials for this type of functional food.

We assessed the effect of ingestion of green tea (GT) extract along with a low-energy diet (LED) on resting energy expenditure (REE), substrate oxidation and body weight as GT has been shown to increase energy expenditure and fat oxidation in the short term in both animals and people. Forty-six overweight women (BMI 27·6 (sd 1·8) kg/m2) were fed in energy balance from day 1 to day 3, followed by a LED with GT (1125 mg tea catechins +225 mg caffeine/d) or placebo (PLAC) from day 4 to day 87. Caffeine intake was standardised to 300 mg/d. Energy expenditure was measured on days 4 and 32. Reductions in weight (4·19 (sd 2·0) kg PLAC, 4·21 (sd 2·7) kg GT), BMI, waist:hip ratio, fat mass and fat-free mass were not statistically different between treatments. REE as a function of fat-free mass and fat mass was significantly reduced over 32 d in the PLAC group (P<0·05) but not in the GT group. Dietary restraint increased over time (P<0·001) in both groups, whereas disinhibition and general hunger decreased (P<0·05). The GT group became more hungry over time and less thirsty, and showed increased prospective food consumption compared with PLAC (P<0·05). Taken together, the ingestion of GT along with a LED had no additional benefit for any measures of body weight or body composition. Although the decrease in REE as a function of fat-free mass and fat mass was not significant with GT treatment, whereas it was with PLAC treatment, no significant effect of treatment over time was seen, suggesting that a robust limitation of REE reduction during a LED was not achieved by GT.