Recent Research Papers on
Author: Adrian B. Hodgson, Rebecca K. Randell, and Asker E. Jeukendrup
Green tea is made from the leaves of the Camellia sinensis L plant, which is rich in polyphenol catechins and caffeine. There is increasing interest in the potential role of green tea extract (GTE) in fat metabolism and its influence on health and exercise performance. A number of studies have observed positive effects of GTE on fat metabolism at rest and during exercise, following both shorter and longer term intake. However, overall, the literature is inconclusive. The fact that not all studies observed effects may be related to differences in study designs, GTE bioavailability, and variation of the measurement (fat oxidation). In addition, the precise mechanisms of GTE in the human body that increase fat oxidation are unclear. The often-cited in vitro catechol-O-methyltransferase mechanism is used to explain the changes in substrate metabolism with little in vivo evidence to support it. Also, changes in expression of fat metabolism genes with longer term GTE intake have been implicated at rest and with exercise training, including the upregulation of fat metabolism enzyme gene expression in the skeletal muscle and downregulation of adipogenic genes in the liver. The exact molecular signaling that activates changes to fat metabolism gene expression is unclear but may be driven by PPAR-γ coactivator 1-α and PPARs. However, to date, evidence from human studies to support these adaptations is lacking. Clearly, more studies have to be performed to elucidate the effects of GTE on fat metabolism as well as improve our understanding of the underlying mechanisms.
Author: Kai Liu, Rui Zhou, Bin Wang, Ka Chen, Lin-Ying Shi, Jun-Dong Zhu, and Man-Tian Mi
Background: The results of studies investigating the effect of green tea on glucose control and insulin sensitivity in humans are inconsistent. Objective: We aimed to quantitatively evaluate the effect of green tea on glucose control and insulin sensitivity. Design: We performed a strategic literature search of PubMed, EMBASE, and the Cochrane Library (updated to January 2013) for randomized controlled trials that evaluated the effects of green tea and green tea extract on glucose control and insulin sensitivity. Study quality was assessed by using the Jadad scale. Weighted mean differences were calculated for net changes in glycemic measures by using fixed-effects or random-effects models. We conducted prespecified subgroup and sensitivity analyses to explore potential heterogeneity. Meta-regression analyses were conducted to investigate dose effects of green tea on fasting glucose and insulin concentrations. Results: Seventeen trials comprising a total of 1133 subjects were included in the current meta-analysis. Green tea consumption significantly reduced the fasting glucose and hemoglobin A1c (Hb A1c) concentrations by −0.09 mmol/L (95% CI: −0.15, −0.03 mmol/L; P < 0.01) and −0.30% (95% CI: −0.37, −0.22%; P < 0.01), respectively. Further stratified analyses from high Jadad score studies showed that green tea significantly reduced fasting insulin concentrations (−1.16 μIU/mL; 95% CI: −1.91, −0.40 μIU/mL; P = 0.03). Conclusions: This meta-analysis suggested that green tea had favorable effects, ie, decreased fasting glucose and Hb A1c concentrations. Subgroup analyses showed a significant reduction in fasting insulin concentrations in trials with high Jadad scores.
Author: Rick Hursel and Margriet S Westerterp-Plantenga
Maintaining the level of daily energy expenditure during weight loss and weight maintenance is as important as maintaining satiety while decreasing energy intake. In this context, different catechin- and caffeine-rich teas (CCRTs), such as green, oolong, and white teas, as well as caffeine have been proposed as tools for maintaining or enhancing energy expenditure and for increasing fat oxidation. Tea polyphenols have been proposed to counteract the decrease in metabolic rate that is usually present during weight loss. Their effects may be of particular importance during weight maintenance after weight loss. Although the thermogenic effect of CCRT has the potential to produce significant effects on these metabolic targets as well as on fat absorption and energy intake, possibly via its impact on the gut microbiota and gene expression, a clinically meaningful outcome also depends on compliance by the subjects. Limitations to this approach require further examination, including moderating factors such as genetic predisposition, habitual caffeine intake, and catechin composition and dose. Nevertheless, CCRTs may be useful agents that could help in preventing a positive energy balance and obesity.
Author: Xin-Xin Zheng, Yan-Lu Xu, Shao-Hua Li, Rutai Hui, Yong-Jian Wu, and Xiao-Hong Huang
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 (−1.48 mg/dL; 95% CI: −2.57, −0.40 mg/dL) decreased significantly with GTCs with or without caffeine, whereas FBI (0.04 μU/mL; 95% CI: −0.36, 0.45 μU/mL), Hb A1c (−0.04%; 95% CI: −0.15, 0.08%), and HOMA-IR (−0.05; 95% CI: −0.37, 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 well-designed trials are needed in the future.
Author: Kashif M. Munir , Sruti Chandrasekaran , Feng Gao , Michael J. Quon
The rising epidemic of diabetes is a pressing issue in clinical medicine worldwide from both healthcare and economic perspectives. This is fueled by overwhelming increases in the incidence and prevalence of obesity. Obesity and diabetes are characterized by both insulin resistance and endothelial dysfunction that lead to substantial increases in cardiovascular morbidity and mortality. Reciprocal relationships between insulin resistance and endothelial dysfunction tightly link metabolic diseases including obesity and diabetes with their cardiovascular complications. Therefore, therapeutic approaches that target either insulin resistance or endothelial dysfunction alone are likely to simultaneously improve both metabolic and cardiovascular pathophysiology and disease outcomes. Moreover, combination therapies with agents targeting distinct mechanisms are likely to have additive or synergistic benefits. Conventional therapies for diabetes and its cardiovascular complications that are both safe and effective are insufficient to meet rising demand. Large, robust, epidemiologic studies demonstrate beneficial metabolic and cardiovascular health effects for many functional foods containing various polyphenols. However, precise molecular mechanisms of action for food polyphenols are largely unknown. Moreover, translation of these insights into effective clinical therapies has not been fully realized. Nevertheless, some functional foods are likely sources for safe and effective therapies and preventative strategies for metabolic diseases and their cardiovascular complications. In this review, we emphasize recent progress in elucidating molecular, cellular, and physiological actions of polyphenols from green tea (EGCG), cocoa (ECG), and citrus fruits (hesperedin) that are related to improving metabolic and cardiovascular pathophysiology. We also discuss a rigorous comprehensive approach to studying functional foods that is essential for developing novel, effective, and safe medications derived from functional foods that will complement existing conventional drugs.
Author: Hae-Suk Kim, Vedrana Montana, Hyun-Ju Jang, Vladimir Parpura and Jeong-a Kim
Epigallocatechin gallate (EGCG) is a major polyphenol in green tea that has beneficial effects in the prevention of cardiovascular disease. Autophagy is a cellular process that protects cells from stressful conditions. To determine whether the beneficial effect of EGCG is mediated by a mechanism involving autophagy, the roles of the EGCG-stimulated autophagy in the context of ectopic lipid accumulation were investigated. Treatment with EGCG increased formation of LC3-II and autophagosomes in primary bovine aortic endothelial cells (BAEC). Activation of calmodulin-dependent protein kinase kinase β was required for EGCG-induced LC3-II formation, as evidenced by the fact that EGCG-induced LC3-II formation was significantly impaired by knockdown of calmodulin-dependent protein kinase kinase β. This effect is most likely due to cytosolic Ca(2+) load. To determine whether EGCG affects palmitate-induced lipid accumulation, the effects of EGCG on autophagic flux and co-localization of lipid droplets and autophagolysosomes were examined. EGCG normalized the palmitate-induced impairment of autophagic flux. Accumulation of lipid droplets by palmitate was markedly reduced by EGCG. Blocking autophagosomal degradation opposed the effect of EGCG in ectopic lipid accumulation, suggesting the action of EGCG is through autophagosomal degradation. The mechanism for this could be due to the increased co-localization of lipid droplets and autophagolysosomes. Co-localization of lipid droplets with LC3 and lysosome was dramatically increased when the cells were treated with EGCG and palmitate compared with the cells treated with palmitate alone. Collectively, these findings suggest that EGCG regulates ectopic lipid accumulation through a facilitated autophagic flux and further imply that EGCG may be a potential therapeutic reagent to prevent cardiovascular complications.
Author: Johanna T Dwyer and Julia Peterson
There is a need to evaluate the evidence about the health effects of tea flavonoids and to provide valid, specific, and actionable tea consumption information to consumers. Emerging evidence suggests that the flavonoids in tea may be associated with beneficial health outcomes, whereas the benefits and risks of tea extracts and supplements are less well known. The next steps in developing tea science should include a focus on the most promising leads, such as reducing the risk of cardiovascular disease and stroke, rather than pursuing smaller, more diffuse studies of many different health outcomes. Future tea research should also include the use of common reference standards, better characterization of intervention products, and application of batteries of biomarkers of intakes and outcomes across studies, which will allow a common body of evidence to be developed. Mechanistic studies should determine which tea bioactive constituents have effects, whether they act alone or in combination, and how they influence health. Clinical studies should use well-characterized test products, better descriptions of baseline diets, and validated biomarkers of intake and disease risk reduction. There should be more attention to careful safety monitoring and adverse event reporting. Epidemiologic investigations should be of sufficient size and duration to detect small effects, involve populations most likely to benefit, use more complete tea exposure assessment, and include both intermediary markers of risk as well as morbidity and mortality outcomes. The construction of a strong foundation of scientific evidence on tea and health outcomes is essential for developing more specific and actionable messages on tea for consumers.
Author: Hyun-Ju Jang , Simone D. Ridgeway , Jeong-a Kim
Insulin resistance, a hallmark of metabolic disorders, is a risk factor for diabetes and cardiovascular disease. Impairment of insulin responsiveness in vascular endothelium contributes to insulin resistance. The reciprocal relationship between insulin resistance and endothelial dysfunction augments the pathophysiology of metabolism and cardiovascular functions. The most abundant green tea polyphenol, epigallocatechin-3-gallate (EGCG), has been shown to have vasodilator action in vessels by activation of endothelial nitric oxide synthase (eNOS). However, it is not known whether EGCG has a beneficial effect in high-fat diet (HFD)-induced endothelial dysfunction. Male C57BL/6J mice were fed either a normal chow diet (NCD) or HFD with or without EGCG supplement (50 mg·kg(-1)·day(-1)) for 10 wk. Mice fed a HFD with EGCG supplement gained less body weight and showed improved insulin sensitivity. In vehicle-treated HFD mice, endothelial function was impaired in response to insulin but not to acetylcholine, whereas the EGCG-treated HFD group showed improved insulin-stimulated vasodilation. Interestingly, EGCG intake reduced macrophage infiltration into aortic tissues in HFD mice. Treatment with EGCG restored the insulin-stimulated phosphorylation of eNOS, insulin receptor substrate-1 (IRS-1), and protein kinase B (Akt), which was inhibited by palmitate (200 μM, 5 h) in primary bovine aortic endothelial cells. From these results, we conclude that supplementation of EGCG improves glucose tolerance, insulin sensitivity, and endothelial function. The results suggest that EGCG may have beneficial health effects in glucose metabolism and endothelial function through modulating HFD-induced inflammatory response.
Author: Yoshihiro Kokubo, Hiroyasu Iso, Isao Saito, Kazumasa Yamagishi, Hiroshi Yatsuya, Junko Ishihara, Manami Inoue, Shoichiro Tsugane
Background and Purpose—Few prospective studies have examined the impact of both green tea and coffee consumption on strokes. We investigated the association of the combination of those consumption with stroke incidence in a general population. Methods—We studied 82 369 Japanese (aged 45–74 years; without cardiovascular disease [CVD] or cancer in 1995 and 1998 for Cohort I and II, respectively) who received 13 years of mean follow-up through the end of 2007. Green tea and coffee consumption was assessed by self-administered food frequency questionnaire at baseline. Results—In the 1 066 718 person-years of follow-up, we documented the incidence of strokes (n=3425) and coronary heart disease (n=910). Compared with seldom drinking green tea, the multivariable-adjusted hazard ratios (95% confidence intervals) of all strokes were 0.86 (0.78–0.95) and 0.80 (0.73–0.89) in green tea 2 to 3 and ≥4 cups/d, respectively. Higher green tea consumption was associated with inverse risks of CVD and strokes subtypes. Compared with seldom drinking coffee, the multivariable-adjusted hazard ratios (95% confidence intervals) of all strokes were 0.89 (0.80–0.99), 0.80 (0.72–0.90), and 0.81 (0.72–0.91) for coffee 3 to 6 times/week and 1 and ≥2 times/day, respectively. Coffee consumption was associated with an inverse risk of CVD and cerebral infarction. Higher green tea or coffee consumption reduced the risks of CVD and stroke subtypes (especially in intracerebral hemorrhage, P for interaction between green tea and coffee=0.04). None of the significant association was observed in coronary heart disease. Conclusions—Higher green tea and coffee consumption were inversely associated with risk of CVD and stroke in general population.
Peracetylated (−)-epigallocatechin-3-gallate (AcEGCG) potently prevents skin carcinogenesis by suppressing the PKD1-dependent signaling pathway in CD34 + skin stem cells and skin tumors
Author: Yi-Shiou Chiou, Shengmin Sang, Kuang-Hung Cheng, Chi-Tang Ho, Ying-Jan Wang and Min-Hsiung Pan
During the process of skin tumor promotion, expression of the cutaneous cancer stem cell (CSC) marker CD34 + is required for stem cell activation and tumor formation. A previous study has shown that activation of protein kinase D1 (PKD1) is involved in epidermal tumor promotion; however, the signals that regulate CSCs in skin carcinogenesis have not been characterized. This study was designed to investigate the chemopreventive potential of peracetylated (−)-epigallocatechin-3-gallate (AcEGCG) on 7,12-dimethylbenz[a]-anthracene (DMBA)-initiated and 12- O -tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumorigenesis in ICR mice and to elucidate the possible mechanisms involved in the inhibitory action of PKD1 on CSCs. We demonstrated that topical application of AcEGCG before TPA treatment can be more effective than EGCG in reducing DMBA/TPA-induced tumor incidence and multiplicity. Notably, AcEGCG not only inhibited the expression of p53, p21, c-Myc, cyclin B, p-CDK1 and Cdc25A but also restored the activation of extracellular signal-regulated kinase 1/2 (ERK1/2), which decreased DMBA/TPA-induced increases in tumor proliferation and mitotic index. To clarify the role of PKD1 in cell proliferation and tumorigenesis, we studied the expression and activation of PKD1 in CD34 + skin stem cells and skin tumors. We found that PKD1 was strongly expressed in CD34 + cells and that pretreatment with AcEGCG markedly inhibited PKD1 activation and CD34 + expression. More importantly, pretreatment with AcEGCG remarkably suppressed nuclear factor-kappaB, cyclic adenosine 3′,5′-monophosphate-responsive element-binding protein (CREB) and CCAAT-enhancer-binding protein (C/EBPs) activation by inhibiting the phosphorylation of c-Jun-N-terminal kinase 1/2, p38 and phosphatidylinositol 3-kinase (PI3K)/Akt and by attenuating downstream target gene expression, including inducible nitric oxide synthase, cyclooxygenase-2, ornithine decarboxylase and vascular endothelial growth factor. Moreover, this is the first study to demonstrate that AcEGCG is a CD34 + and PKD1 inhibitor in the multistage mouse skin carcinogenesis model. Overall, our results powerfully suggest that AcEGCG could be developed into a novel chemopreventive agent and that PKD1 may be a preventive and therapeutic target for skin cancer in clinical settings.