Effects of green tea and EGCG on cardiovascular and metabolic health.
Since ancient times green tea has been considered a health-promoting beverage. In recent years, scientists throughout the world have investigated the potential benefits of green tea and its most abundant catechin, epigallocatechin gallate (EGCG). The anti-cancer effects of green tea and EGCG were the focus of early research, and encouraging data from in vitro, animal model, and human studies have emerged. Due to the dominant role of cardiovascular disease and the dramatic rise of obesity and type 2 diabetes mellitus as major and interlinked healthcare problems, green tea and EGCG are increasingly being investigated in these areas. Dose-response relationships observed in several epidemiological studies have indicated that pronounced cardiovascular and metabolic health benefits can be obtained by regular consumption of 5-6 or more cups of green tea per day. Furthermore, intervention studies using similar amounts of green tea, containing 200-300 mg of EGCG, have demonstrated its usefulness for maintaining cardiovascular and metabolic health. Additionally, there are numerous in vivo studies demonstrating that green tea and EGCG exert cardiovascular and metabolic benefits in these model systems. Therefore, green tea and EGCG can be regarded as food components useful for the maintenance of cardiovascular and metabolic health. To prove the effectiveness for disease prevention or treatment, several multi-center, long-term clinical studies investigating the effects of one precisely-defined green tea product on cardiovascular and metabolic endpoints would be necessary. The aim of this manuscript is to provide an overview of the research investigating the effects of green tea and green tea catechins on cardiovascular and metabolic health.
J Am Coll Nutr. 2007 Aug;26(4):373S-388S
Metabolism of green tea catechins: an overview.
Green tea is one of the most popular beverages worldwide. Its major components include (-)-epicatechin ((-)-EC), (-)-epicatechin-3-gallate (ECG) (-)-epigallocatechin (EGC) and (-)-epigallocatechin-3-gallate (EGCG). It has demonstrated strong antioxidative, anti-inflammatory and anti-cancerous properties and attracted a great deal of interest over last several years. However, there is some discrepancy between the results from human pidemiological studies and cultured cell and animal models. Two reasons for its limited in vivo activities have been considered: metabolism and bioavailability. Recent studies have demonstrated that green tea catechins undergo methylation, glucuronidation and sulfation in in vitro systems and in animals and in humans. It has been also found that efflux transporters Pgp, MRP1 and MRP2 play roles in the absorption and excretion of green tea catechins. Several processes including intestinal metabolism, microbial metabolism, hepatic metabolism and chemical degradation have been found to be involved in the fate of green tea, and to be responsible for its low availability in animals, and most likely also in humans. Pharmacokinetics, absorption, distribution, drug metabolism and excretion properties of green tea provide a better understanding for its in vivo activities. In this article, drug metabolism and microbial metabolism of green tea catechins in in vitro systems and in animals and in humans will be reviewed. It also covers the factors affecting their biotransformation and bioavailability: drug-drug inhibitory and inductive interactions of phase I and phase II enzymes, inhibition of non-drug-metabolizing enzymes, transporters, chemical instability, epimerization and interindividual variability.
Curr Drug Metab. 2006 Oct;7(7):755-809
Nutraceutical antioxidants as novel neuroprotective agents.
A variety of antioxidant compounds derived from natural products (nutraceuticals) have demonstrated neuroprotective activity in either in vitro or in vivo models of neuronal cell death or neurodegeneration, respectively. These natural antioxidants fall into several distinct groups based on their chemical structures: (1) flavonoid polyphenols like epigallocatechin 3-gallate (EGCG) from green tea and quercetin from apples; (2) non-flavonoid polyphenols such as curcumin from turmeric and resveratrol from grapes; (3) phenolic acids or phenolic diterpenes such as rosmarinic acid or carnosic acid, respectively, both from rosemary; and (4) organosulfur compounds including the isothiocyanate, L-sulforaphane, from broccoli and the thiosulfonate allicin, from garlic. All of these compounds are generally considered to be antioxidants. They may be classified this way either because they directly scavenge free radicals or they indirectly increase endogenous cellular antioxidant defenses, for example, via activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2) transcription factor pathway. Alternative mechanisms of action have also been suggested for the neuroprotective effects of these compounds such as modulation of signal transduction cascades or effects on gene expression. Here, we review the literature pertaining to these various classes of nutraceutical antioxidants and discuss their potential therapeutic value in neurodegenerative diseases.
Molecules. 2010 Nov 3;15(11):7792-814
Comparative Evaluation of Different Doses of Green Tea Extract Alone and in Combination with Sulfasalazine in Experimentally Induced Inflammatory Bowel Disease in Rats.
BACKGROUND: The exact etiopathology of inflammatory bowel disease is still unclear. Most of the therapies present are directed towards symptomatic improvement. Surgical therapy in the form of restorative proctocolectomy is reserved for the terminal stage disease, which is unresponsive to medical therapy. The present study was conducted to evaluate the effect of green tea in experimentally induced inflammatory bowel disease. METHODS: A total of 36 animals were included in the study. The animals were divided into five groups (n = 6): Group I-Vehicle (ethanol), group II-TNBS + ethanol, group III-green tea-treated group was divided into two sub-groups on the basis of different doses: group IIIA-TNBS + green tea (35 mg/kg), group IIIB-TNBS + green tea (70 mg/kg), group IV-TNBS + sulfasalazine (360 mg/kg), group V-TNBS + sulfasalazine (360 mg/kg) + green tea (least effective dose found in group III). After completion of 2 weeks of treatment, the rats were killed under ether anesthesia by cervical dislocation for assessment of intestinal inflammation, histological analysis, myeloperoxidase assay, malondialdehyde assay, and TNF- estimation. RESULTS: The study showed that green tea alone and in combination with sulfasalazine reduced inflammatory changes induced by tri nitro benzene sulfonic acid in rats. This reduction is associated with reduced malondialdehyde, lipid peroxidation, and TNF-. This correlates well with both gross morphological and histopathological scores. CONCLUSIONS: The authors concluded that a combination of green tea extract with sulfasalazine showed greater efficacy than single drug treatment.
Dig Dis Sci. 2010 Nov 17
TLR4 signaling inhibitory pathway induced by green tea polyphenol epigallocatechin-3-gallate through 67-kDa laminin receptor.
Epigallocatechin-3-gallate (EGCG), a major active polyphenol of green tea, has been shown to downregulate inflammatory responses in macrophages; however, the underlying mechanism has not been understood. Recently, we identified the 67-kDa laminin receptor (67LR) as a cell-surface EGCG receptor that mediates the anticancer action of EGCG at physiologically relevant concentrations (0.1-1 microM). In this study, we show the molecular basis for the downregulation of TLR4 signal transduction by EGCG at 1 microM in macrophages. Anti-67LR Ab treatment or RNA interference-mediated silencing of 67LR resulted in abrogation of the inhibitory action of EGCG on LPS-induced activation of downstream signaling pathways and target gene expressions. Additionally, we found that EGCG reduced the TLR4 expression through 67LR. Interestingly, EGCG induced a rapid upregulation of Toll-interacting protein (Tollip), a negative regulator of TLR signaling, and this EGCG action was prevented by 67LR silencing or anti-67LR Ab treatment. RNA interference-mediated silencing of Tollip impaired the TLR4 signaling inhibitory activity of EGCG. Taken together, these findings demonstrate that 67LR plays a critical role in mediating anti-inflammatory action of a physiologically relevant EGCG, and Tollip expression could be modulated through 67LR. These results provide a new insight into the understanding of negative regulatory mechanisms for the TLR4 signaling pathway and consequent inflammatory responses that are implicated in the development and progression of many chronic diseases.
J Immunol. 2010 Jul 1;185(1):33-45
Consumption of green tea causes rapid increase in plasma antioxidant power in humans.
Green tea contains polyphenolic antioxidants that have shown anticarcinogenic properties in animal and in vitro experimental studies. Current data regarding absorption and bioavailability of tea antioxidants in humans, however, are conflicting. In this study, plasma and urine antioxidant power after ingestion of green tea was measured using the ferric reducing/antioxidant power (FRAP) assay (US patent pending) to assess absorption, systemic distribution, and renal excretion of green tea antioxidants in healthy adults. Results showed that absorption of green tea antioxidants was rapid, with peak increase in plasma FRAP of around 4% at 40 minutes after ingestion: mean increase was 44 +/- 9 (SE) mumol/l. Excretion of polyphenolic antioxidants was also fast, peaking at 60-90 minutes, with significant correlation between urinary FRAP values and urinary total phenolic concentrations (r = 0.845, p < 0.001). In control studies, no increase in plasma or urine FRAP values was seen after intake of water. Although the amount of antioxidants absorbed was relatively small and the increase in plasma antioxidant power was of short duration, results demonstrate that some potentially anticarcinogenic polyphenolic antioxidants in green tea enter the systemic circulation soon after ingestion and cause a significant increase in plasma antioxidant status. This increase may, in turn, lower oxidative damage to DNA and so decrease risk of cancer.
Nutr Cancer. 1999;34(1):83-7
Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals.
PURPOSE: Green tea and green tea polyphenols have been shown to possess cancer preventive activities in preclinical model systems. In preparation for future green tea intervention trials, we have conducted a clinical study to determine the safety and pharmacokinetics of green tea polyphenols after 4 weeks of daily p.o. administration of epigallocatechin gallate (EGCG) or Polyphenon E (a defined, decaffeinated green tea polyphenol mixture). In an exploratory fashion, we have also determined the effect of chronic green tea polyphenol administration on UV-induced erythema response. EXPERIMENTAL DESIGN: Healthy participants with Fitzpatric skin type II or III underwent a 2-week run-in period and were randomly assigned to receive one of the five treatments for 4 weeks: 800 mg EGCG once/day, 400 mg EGCG twice/day, 800 mg EGCG as Polyphenon E once/day, 400 mg EGCG as Polyphenon E twice/day, or a placebo once/day (8 subjects/group). Samples were collected and measurements performed before and after the 4-week treatment period for determination of safety, pharmacokinetics, and biological activity of green tea polyphenol treatment. RESULTS: Adverse events reported during the 4-week treatment period include excess gas, upset stomach, nausea, heartburn, stomach ache, abdominal pain, dizziness, headache, and muscle pain. All of the reported events were rated as mild events. For most events, the incidence reported in the polyphenol-treated groups was not more than that reported in the placebo group. No significant changes were observed in blood counts and blood chemistry profiles after repeated administration of green tea polyphenol products. There was a >60% increase in the area under the plasma EGCG concentration-time curve after 4 weeks of green tea polyphenol treatment at a dosing schedule of 800 mg once daily. No significant changes were observed in the pharmacokinetics of EGCG after repeated green tea polyphenol treatment at a regimen of 400 mg twice daily. The pharmacokinetics of the conjugated metabolites of epigallocatechin and epicatechin were not affected by repeated green tea polyphenol treatment. Four weeks of green tea polyphenol treatment at the selected dose and dosing schedule did not provide protection against UV-induced erythema. CONCLUSIONS: We conclude that it is safe for healthy individuals to take green tea polyphenol products in amounts equivalent to the EGCG content in 8-16 cups of green tea once a day or in divided doses twice a day for 4 weeks. There is a >60% increase in the systemic availability of free EGCG after chronic green tea polyphenol administration at a high daily bolus dose (800 mg EGCG or Polyphenon E once daily).
Clin Cancer Res. 2003 Aug 15;9(9):3312-9
Bioavailability and antioxidant activity of tea flavanols after consumption of green tea, black tea, or a green tea extract supplement.
BACKGROUND: Green and black tea polyphenols have been extensively studied as cancer chemopreventive agents. Many in vitro experiments have supported their strong antioxidant activity. Additional in vivo studies are needed to examine the pharmacokinetic relation of absorption and antioxidant activity of tea polyphenols administered in the form of green or black tea or tea extract supplements. OBJECTIVE: The purpose of this study was to compare the pharmacokinetic disposition of tea polyphenols and their effect on the antioxidant capacity in plasma 8 h after a bolus consumption of either green tea, black tea, or a green tea extract supplement. DESIGN: Thirty healthy subjects were randomly assigned to 3 different sequences of green tea, black tea, or a green tea extract supplement in a 3 x 3 crossover design with a 1-wk washout period in between treatments. RESULTS: Flavanol absorption was enhanced when tea polyphenols were administered as a green tea supplement in capsule form and led to a small but significant increase in plasma antioxidant activity compared with when tea polyphenols were consumed as black tea or green tea. All 3 interventions provided similar amounts of (-)-epigallocatechin-3-gallate. CONCLUSIONS: Our observations suggest that green tea extract supplements retain the beneficial effects of green and black tea and may be used in future chemoprevention studies to provide a large dose of tea polyphenols without the side effects of caffeine associated with green and black tea beverages.
Am J Clin Nutr. 2004 Dec;80(6):1558-64
Green tea and cancer prevention.
Extracts of green tea and green tea polyphenols have exhibited inhibitory effects against the formation and development of tumors at different organ sites in animals. These include animal models for skin, lung, oral cavity, esophagus, stomach, intestine, colon, liver, pancreas, bladder, mammary gland, and prostate cancers. In addition to suppressing cell proliferation, promoting apoptosis, and modulating signaling transduction, green tea polyphenols, especially (-)-epigallocatechin-3-gallate, also inhibit cell invasion, angiogenesis, and metastasis. This article reviews data on the cancer preventive activities of green tea polyphenols, possible mechanisms involved, and the relationship between green tea consumption and human cancer risk.
Nutr Cancer. 2010;62(7):931-7
Phase I study of green tea extract in patients with advanced lung cancer.
PURPOSE: Epidemiologic studies suggest that consumption of green tea may have a protective effect against the development of several cancers. Preclinical studies of green tea and its polyphenolic components have demonstrated antimutagenic and anticarcinogenic activity, and inhibition of growth of tumor cell lines and animal tumor models, including lung cancer. Green tea may also have chemopreventive properties, and enhancement of cytotoxicity of chemotherapeutic agents has been demonstrated. This trial was designed to determine the maximum tolerated dose (MTD) of green tea extract (GTE) in patients with advanced lung cancer. METHODS: A total of 17 patients with advanced lung cancer were registered to receive once-daily oral dosing of GTE at a starting dose of 0.5 g/m2 per day, with an accelerated dose-escalation scheme. RESULTS: On this schedule, the MTD of GTE was 3 g/m2 per day, and at this dose, GTE was well tolerated with no grade 3 or 4 toxicity seen. Dose-limiting toxicities were diarrhea, nausea and hypertension. No objective responses were seen in this trial. Seven patients had stable disease ranging from 4 to 16 weeks; no patient remained on therapy longer than 16 weeks due to the development of progressive disease. CONCLUSIONS: This study suggests that while relatively nontoxic at a dose of 3 g/m2 per day, GTE likely has limited activity as a cytotoxic agent, and further study of GTE as a single-agent in established malignancies may not be warranted. Further studies should focus on the potential chemopreventive and chemotherapy-enhancing properties of GTE.
Cancer Chemother Pharmacol. 2005 Jan;55(1):33-8