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LE Magazine April 2007

Green tea

Green tea and thermogenesis: interactions between catechin-polyphenols, caffeine and sympathetic activity.

The thermogenic effect of tea is generally attributed to its caffeine content. We report here that a green tea extract stimulates brown adipose tissue thermogenesis to an extent which is much greater than can be attributed to its caffeine content per se, and that its thermogenic properties could reside primarily in an interaction between its high content in catechin-polyphenols and caffeine with sympathetically released noradrenaline (NA). Since catechin-polyphenols are known to be capable of inhibiting catechol-O-methyl-transferase (the enzyme that degrades NA), and caffeine to inhibit trancellular phosphodiesterases (enzymes that break down NA-induced cAMP), it is proposed that the green tea extract, via its catechin-polyphenols and caffeine, is effective in stimulating thermogenesis by relieving inhibition at different control points along the NA-cAMP axis. Such a synergistic interaction between catechin-polyphenols and caffeine to augment and prolong sympathetic stimulation of thermogenesis could be of value in assisting the management of obesity.

Int J Obes Relat Metab Disord. 2000 Feb;24(2):252-8

Green tea extract thermogenesis-induced weight loss by epigallocatechin gallate inhibition of catechol-O-methyltransferase.

Epidemiological studies have shown that intake of tea catechins is associated with a lower risk of cardiovascular disease. The antioxidative activity of tea-derived catechins has been extensively studied. Reports have shown that green tea extract intake is associated with increased weight loss due to diet-induced thermogenesis, which is generally attributed to the catechin epigallocatechin gallate. That catechin-polyphenols are known to be capable of inhibiting catechol-O-methyltransferase (the enzyme that degrades norepinephrine) is a possible explanation for why the green tea extract is effective in stimulating thermogenesis by epigallocatechin gallate to augment and prolong sympathetic stimulation of thermogenesis. Knowledge about thermogenesis-induced weight loss produced by green tea’s epigallocatechin gallate and its ability to inhibit catechol-O-methyltransferase is important for health benefits and for prolonging the action of norepinephrine in the synaptic cleft.

J Med Food. 2006 Winter;9(4):451-8

Effects on blood pressure of drinking green and black tea.

BACKGROUND: The flavonoid components of tea have been associated in epidemiological studies with a decreased risk of cardiovascular disease. Flavonoids have been shown to have antioxidant and vasodilator effects in vitro; we therefore postulated that drinking green or black tea attenuates the well-characterized acute pressor response to caffeine and lowers blood pressure during regular consumption. OBJECTIVE: To determine whether green and black tea can attenuate the transient pressor effect of caffeine, or lower blood pressure during regular consumption. METHODS: In the first study, the acute effects of four hot drinks - green tea and black tea (at a dose equivalent to four standard cups), water matched to the teas for caffeine content (‘caffeine’) and water - were assessed in 20 normotensive men using a Latin-Square designed study. Clinic blood pressure was measured before and 30 and 60 min after each drink had been ingested. In the second study, the effects on blood pressure of regular green and black tea ingestion were examined in 13 subjects with high-normal systolic blood pressure and mild systolic hypertension (systolic blood pressure in the range 130-150 mmHg) using a three-period crossover study. Five cups per day of green tea, black tea and caffeine (in hot water and matched to the teas) were consumed for 7 days each, in random order. Twenty-four hour ambulatory blood pressure was measured at the end of each seven-day intervention. Results are presented as means and 95% confidence intervals (CI). RESULTS: An acute pressor response to caffeine was observed. Relative to caffeine, there were further acute increases in systolic and diastolic blood pressure at 30 min among those drinking green tea [5.5 mmHg (95%CI -1.4 to 12.4) and 3.1 mmHg (95%CI -0.1 to 6.3), respectively] and black tea [10.7 mmHg (95%CI 4.0 to 17.4) and 5.1 mmHg (95%CI 1.8 to 8.4), respectively]. The changes in blood pressure at 60 min were not significant The effect on 24-h ambulatory systolic and diastolic blood pressure of regular drinking of green tea [increases of 1.7 mmHg (95%CI -1.6 to 5.0) and 0.9 mmHg (95%CI -1.3 to 3.1), respectively] or black tea [increase of 0.7 mmHg (95%CI -2.6 to 4.0) and decrease of 0.7 mmHg (95%CI -2.9 to 1.5), respectively] was not significant relative to caffeine. CONCLUSIONS: Contrary to our initial hypothesis, tea ingestion caused larger acute increases in blood pressure than caffeine alone. However, any acute effects of tea on blood pressure did not translate into significant alterations in ambulatory blood pressure during regular tea consumption.

J Hypertens. 1999 Apr;17(4):457-63

Green tea extract improves running endurance in mice by stimulating lipid utilization during exercise.

A series of polyphenols known as catechins are abundant in green tea, which is consumed mainly in Asian countries. The effects of catechin-rich green tea extract (GTE) on running endurance and energy metabolism during exercise in BALB/c mice were investigated. Mice were divided into four groups: nonexercise control, exercise control (Ex-cont), exercise+0.2% GTE, and exercise+0.5% GTE groups. Treadmill running time to exhaustion, plasma biochemical parameters, skeletal muscle glycogen content, beta-oxidation activity, and malonyl-CoA content immediately after exercise were measured at 8-10 wk after the initiation of the experiment. Oxygen consumption and respiratory exchange ratio were measured using indirect calorimetry. Running times to exhaustion in mice fed 0.5% GTE were 30% higher than in Ex-cont mice and were accompanied by a lower respiratory exchange ratio, higher muscle beta-oxidation activity, and lower malonyl-CoA content. In addition, muscle glycogen content was high in the GTE group compared with the Ex-cont group. Plasma lactate concentrations in mice fed GTE were significantly lower after exercise, concomitant with an increase in free fatty acid concentrations. Catechins, which are the main constituents of GTE, did not show significant effects on peroxisome proliferator-activated receptor-alpha or delta-dependent luciferase activities. These results suggest that the endurance-improving effects of GTE were mediated, at least partly, by increased metabolic capacity and utilization of fatty acid as a source of energy in skeletal muscle during exercise.

Am J Physiol Regul Integr Comp Physiol. 2006 Jun;290(6):R1550-6

Structure-activity relationships of tea compounds against human cancer cells.

The content of the biologically active amino acid theanine in 15 commercial black, green, specialty, and herbal tea leaves was determined as the 2,4-dinitrophenyltheanine derivative (DNP-theanine) by a validated HPLC method. To define relative anticarcinogenic potencies of tea compounds and teas, nine green tea catechins, three black tea theaflavins, and theanine as well as aqueous and 80% ethanol/water extracts of the same tea leaves were evaluated for their ability to induce cell death in human cancer and normal cells using a tetrazolium microculture (MTT) assay. Compared to untreated controls, most catechins, theaflavins, theanine, and all tea extracts reduced the numbers of the following human cancer cell lines: breast (MCF-7), colon (HT-29), hepatoma (liver) (HepG2), and prostate (PC-3) as well as normal human liver cells (Chang). The growth of normal human lung (HEL299) cells was not inhibited. The destruction of cancer cells was also observed visually by reverse phase microscopy. Statistical analysis of the data showed that (a) the anticarcinogenic effects of tea compounds and of tea leaf extracts varied widely and were concentration dependent over the ranges from 50 to 400 mug/mL of tea compound and from 50 to 400 mug/g of tea solids; (b) the different cancer cells varied in their susceptibilities to destruction; (c) 80% ethanol/water extracts with higher levels of flavonoids determined by HPLC were in most cases more active than the corresponding water extracts; and (d) flavonoid levels of the teas did not directly correlate with anticarcinogenic activities. The findings extend related observations on the anticarcinogenic potential of tea ingredients and suggest that consumers may benefit more by drinking both green and black teas. Keywords: HPLC; theanine; catechins; theaflavins; teas; cancer cells; growth inhibition; structure-activity relationships; dietary significance.

J Agric Food Chem. 2007 Jan 24;55(2):243-253

Intracellular signaling network as a prime chemopreventive target of (-)-epigallocatechin gallate.

Chemoprevention is an attempt to use either naturally occurring or synthetic substances or their mixtures to intervene in the progress of carcinogenesis. Recently, it has been shown that some edible phytochemicals alter gene expression, directly or indirectly, thereby regulating the carcinogenic processes. (-)-Epigallocatechin gallate (EGCG), a principal antioxidant derived from green tea, is one of the most extensively investigated chemopreventive phytochemicals. EGCG has been known to block each stage of carcinogenesis by modulating signal transduction pathways involved in cell proliferation, transformation, inflammation, apoptosis, metastasis and invasion. This review addresses the molecular target-based chemoprevention with EGCG by focusing on the common events mediated by transcription factors, such as NF-kappa B, activator protein-1 and nuclear factor erythroid 2 p45-related factor, and upstream kinases involved in the cellular signaling network.

Mol Nutr Food Res. 2006 Feb;50(2):152-9

Green tea polyphenols in the prevention of colon cancer.

Several plant-based nutrients and non-nutrients that can inhibit mutagenesis and proliferation have been identified. Some of the most promising nutrients identified as chemopreventive agents in colon cancer prevention include isoflavones, curcumin, calcium, vitamin D and more recently Green tea polyphenols (GTP). In addition to inhibiting mutagenesis and proliferation, these compounds are relatively non-toxic, are of low cost and can be taken orally or as a part of the daily diet. Epidemiological and laboratory studies have identified epigallocatechin gallate (EGCG) in green tea polyphenols (GTP), as the most potent chemopreventive agent that can induce apoptosis, suppress the formation and growth of human cancers including colorectal cancers (CRC). It is only logical then, that future clinical studies should focus on examining the efficacy of phytochemicals such as EGCG in cancer chemoprevention as an alternative to pharmacological agents, especially in populations where administration of COX-2 inhibitors, Aspirin and NSAIDS is contraindicated. The goal of this review is to provide the rationale, and discuss the use of EGCG in GTP as a chemopreventive agent for prevention of colon carcinogenesis and present evidence for the efficacy and safety of these agents based on epidemiological, animal, in vitro studies and Phase I clinical trials.

Front Biosci. 2007 Jan 1;12:2309-15

Mechanisms of hypolipidemic and anti-obesity effects of tea and tea polyphenols.

Among the health-promoting effects of tea and tea polyphenols, the cancer-chemopreventive effects in various animal model systems have been intensively investigated; meanwhile, the hypolipidemic and antiobesity effects in animals and humans have also become a hot issue for molecular nutrition and food research. It has been demonstrated that the body weights of rats and their plasma triglyceride, cholesterol, and LDL-cholesterol have been significantly reduced by feedings of oolong, black, pu-erh, and green tea leaves to the animals. It has been suggested that the inhibition of growth and suppression of lipogenesis in MCF-7 breast cancer cells may be through down-regulation of fatty acid synthase gene expression in the nucleus and stimulation of cell energy expenditure in the mitochondria. The experimental data indicated that the molecular mechanisms of fatty acid synthase gene suppression by tea polyphenols (EGCG, theaflavins) may invite down-regulation of EGFR/PI3K/Akt/Sp-1 signal transduction pathways.

Mol Nutr Food Res. 2006 Feb;50(2):211-7

Green tea, black tea and breast cancer risk: a meta-analysis of epidemiological studies.

Experimental studies have shown that tea and tea polyphenols have anti-carcinogenic properties against breast cancer. A number of epidemiologic studies, both case-control and cohort in design, have examined the possible association between tea intake and breast cancer development in humans. This meta-analysis included 13 papers which examined populations in eight countries and provided data on consumption of either green tea or black tea, or both in relation to breast cancer risk. Summary odds ratios (ORs) for highest versus non/lowest tea consumption level were calculated based on fixed and random effects models. Heterogeneity between studies was examined via the Q statistics. For green tea, the combined results from the four studies indicated a reduced risk of breast cancer for highest versus non/lowest intake (OR = 0.78, 95% CI = 0.61-0.98). For black tea, conflicting results were observed in case-control versus cohort studies. The combined results from the eight case-control studies showed a minor inverse association between black tea consumption and risk of breast cancer (OR = 0.91, 95% CI = 0.84-0.98). This inverse association was stronger in hospital-based (OR = 0.77, 95% CI = 0.50-1.19) than population-based case-control studies (OR = 0.94, 95% CI = 0.81-1.09). Five cohort studies demonstrated a modest increase in risk associated with black tea intake (OR = 1.15, 95% CI = 1.02-1.31). The results of this meta-analysis indicate a lower risk for breast cancer with green tea consumption. Available data suggest a possible late-stage, promotional effect of black tea on breast carcinogenesis.

Carcinogenesis. 2006 Jul;27(7):1310-5

The effects of green tea consumption on incidence of breast cancer and recurrence of breast cancer: a systematic review and meta-analysis.

BACKGROUND: Green tea is widely used by women for the prevention and treatment of breast cancer. The authors aimed to determine the efficacy of green tea ingestion on the risk of breast cancer development and the risk of breast cancer recurrence. METHODS: The authors conducted a systematic review and meta-analyses of observational studies from systematic searches of 8 electronic data sources and contact with authors. They included studies assessing breast cancer incidence and recurrence. RESULTS: Results: The pooled relative risk (RR) of developing breast cancer for the highest levels of green tea consumption in cohort studies was 0.89 (95% confidence interval [CI], 0.71-1.1; P= .28; I(2)= 0%), and in case control studies, the odds ratio was 0.44 (95% CI, 0.14-1.31; P= .14; I(2)= 47%). The pooled RR of cohort studies for breast cancer recurrence in all stages was 0.75 (95% CI, 0.47-1.19; P= .22; I(2)= 37%). A subgroup analysis of recurrence in stage I and II disease showed a pooled RR in cohort studies of 0.56 (95% CI, 0.38-0.83; P= .004; I2= 0%). Dose-response relationships were evident in only 3 of the 7 studies. CONCLUSION: To date, the epidemiological data indicates that consumption of 5 or more cups of green tea a day shows a non-statistically significant trend towards the prevention of breast cancer development. Evidence indicates that green tea consumption may possibly help prevent breast cancer recurrence in early stage (I and II) cancers. However, conclusions as to the potential therapeutic application of green tea are currently impossible to make due to the small number of studies conducted, the lack of any clinical trial evidence, the lack of a consistent dose-response relationship, and the potential for interaction with standard care.

Integr Cancer Ther. 2005 Jun;4(2):144-55

Black and green teas equally inhibit diabetic cataracts in a streptozotocin-induced rat model of diabetes.

Green and black teas were given at 1.25% in the drinking water to streptozotocin-induced diabetic rats for 3 months. Normal and diabetic control groups were also studied. As expected, diabetic animals had significantly increased glucose in lens and plasma. Lens and red blood cell sorbitol were significantly increased as a result of the aldose reductase pathway activation. Plasma and lens lipid thiobarbituric acid-reactive substances and protein glycation were also significantly elevated. Both teas significantly inhibited diabetic cataracts and caused significant reductions in the biochemical pathway implicated in the development of the pathology. After corrections for glucose, it was found that the teas retard the development of diabetic cataracts by a hypoglycemic effect that in turn inhibits the biochemical indicators of pathology. There were significant correlations between glucose, cataract score, and these indicators. Green tea but not black tea caused a significant decline in triglycerides in the diabetic animals. Tea may be a simple, inexpensive means of preventing or retarding human diabetes and the ensuing complications. Tea also should be investigated as an adjunct therapy for diabetes treatment.

J Agric Food Chem. 2005 May 4;53(9):3710-3

A new approach to managing oral manifestations of Sjogren’s syndrome and skin manifestations of lupus.

Sjogren’s syndrome (SS) is an autoimmune disorder that affects the salivary glands, leading to xerostomia, and the lacrimal glands, resulting in xerophthalmia. Secondary SS is associated with other autoimmune disorders such as systemic rheumatic diseases and systemic lupus erythematosis (SLE), which can affect multiple organs, including the epidermis. Recent studies have demonstrated that green tea polyphenols (GTPs) possess both anti-inflammatory and anti-apoptotic properties in normal human cells. Epidemiological evidence has indicated that, in comparison to the United States, the incidence of SS, clinical xerostomia and lupus is considerably lower in China and Japan, the two leading green tea-consuming countries.Thus, GTPs might be responsible, in part, for geographical differences in the incidence of xerostomia by reducing the initiation or severity of SS and lupus. Consistent with this, molecular, cellular and animal studies indicate that GTPs could provide protective effects against autoimmune reactions in salivary glands and skin. Therefore, salivary tissues and epidermal keratinocytes could be primary targets for novel therapies using GTPs. This review article evaluates the currently available research data on GTPs, focusing on their potential application in the treatment of the oral manifestations of SS and skin manifestations of SLE.

J Biochem Mol Biol. 2006 May 31;39(3):229-39

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