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LE Magazine April 2008

Green Tea

DNA and RNA as new binding targets of green tea catechins.

The significance of catechins, the main constituent of green tea, is being increasingly recognized with regard to cancer prevention. Catechins have been studied for interactions with various proteins, but the mechanisms of the various catechins are not yet elucidated. Based on our previous observation that nucleic acids extracted from catechin-treated cells are colored, we studied whether catechins directly interact with nucleic acids using surface plasmon resonance assay (Biacore) and cold spray ionization-mass spectrometry. These two methods clearly showed that (-)-epigallocatechin gallate (EGCG) binds to both DNA and RNA molecules: the Biacore assay indicated that four catechins bound to DNA oligomers, and cold spray ionization-mass spectrometry analysis showed one to three EGCG molecules bound to single strand 18 mers of DNA and RNA. Moreover, one or two molecules of EGCG bound to double-stranded (AG-CT) oligomers of various nucleotide lengths. These results suggest that multiple binding sites of EGCG are present in DNA and RNA oligomers. Double-stranded DNA (dsDNA) oligomers were detected only as EGCG-bound forms at high temperature, whereas at low temperature both the free and bound forms were detected, suggesting that EGCG protects dsDNA oligomers from dsDNA melting to single-stranded DNA. Because both galloyl and catechol groups of EGCG are essential for DNA binding, both groups seem to hold strands of DNA via their branching structure. These findings reveal for the first time the link between catechins and polynucleotides and will intensify our understanding of the effects of catechins on DNA in terms of cancer prevention.

J Biol Chem. 2006 Jun 23;281(25):17446-56

Green tea catechin as a chemical chaperone in cancer prevention.

Green tea catechins have recently gained significant acceptance as a cancer preventive, and one of the important features of catechins is their interactions with various target molecules. We recently found a functional and structural similarity between catechins and chaperones: Stochastic conformational analysis in silico revealed numerous conformations of (-)-epigallocatechin gallate, (-)-epicatechin gallate and (-)-epigallocatechin, showing a unique flexibility and mobility of the catechin molecules and suggesting the significance of a galloyl group in conformational variation. Since these conformations result in interaction with various types of molecules, we think that green tea catechin induces cancer preventive activity mediated through a chaperone-like property.

Cancer Lett. 2007 Dec 7

Biotransformation of green tea polyphenols and the biological activities r polyphenol constituents, the catechins, have been reported to have many health benefits including the prevention of cancer and heart disease. Many mechanisms of action have been proposed based on in vitro models; however, the importance of most of these mechanisms remains to be determined in vivo. The bioavailability and biotransformation of tea catechins play a key role in determining the importance of various mechanisms in vivo. Likewise, the biological activity and bioavailability of tea catechin metabolites, an understudied area, are important in understanding the potential beneficial effects of tea. In this article, we review the data available on the biotransformation of the tea catechins and the limited data set available on the biological activities of the catechin metabolites. Careful interpretation of available data, carefully designed animal experiments, and integration of bioavailability and biological activity data are needed if the disease preventive activity of tea is to be understood. We hope this article will spark research efforts on some of the important questions regarding tea polyphenol bioavailability, biotransformation, and the biological activities of tea catechin metabolites.

Mol Pharm. 2007 Nov-Dec;4(6):819-25

Anti-obesity effects of green tea: from bedside to bench.

During the last decade, the traditional notion that green tea consumption benefits health has received significant scientific attention and, particularly, the areas of cardiovascular disease and cancer were subject to numerous studies. Due to the ever-growing obesity pandemic, the anti-obesity effects of green tea are being increasingly investigated in cell, animal, and human studies. Green tea, green tea catechins, and epigallocatechin gallate (EGCG) have been demonstrated in cell culture and animal models of obesity to reduce adipocyte differentiation and proliferation, lipogenesis, fat mass, body weight, fat absorption, plasma levels of triglycerides, free fatty acids, cholesterol, glucose, insulin and leptin, as well as to increase beta-oxidation and thermogenesis. Adipose tissue, liver, intestine, and skeletal muscle are target organs of green tea, mediating its anti-obesity effects. Studies conducted with human subjects report reduced body weight and body fat, as well as increased fat oxidation and thermogenesis and thereby confirm findings in cell culture systems and animal models of obesity. There is still a need for well-designed and controlled clinical studies to validate the existing and encouraging human studies. Since EGCG is regarded as the most active component of green tea, its specific effects on obesity should also be investigated in human trials.

Mol Nutr Food Res. 2006 Feb;50(2):176-87

Neurological mechanisms of green tea polyphenols in Alzheimer’s and Parkinson’s diseases.

Tea consumption is varying its status from a mere ancient beverage and a lifestyle habit, to a nutrient endowed with possible prospective neurobiological-pharmacological actions beneficial to human health. Accumulating evidence suggest that oxidative stress resulting in reactive oxygen species generation and inflammation play a pivotal role in neurodegenerative diseases, supporting the implementation of radical scavengers, transition metal (e.g., iron and copper) chelators, and nonvitamin natural antioxidant polyphenols in the clinic. These observations are in line with the current view that polyphenolic dietary supplementation may have an impact on cognitive deficits in individuals of advanced age. As a consequence, green tea polyphenols are now being considered as therapeutic agents in well controlled epidemiological studies, aimed to alter brain aging processes and to serve as possible neuroprotective agents in progressive neurodegenerative disorders such as Parkinson’s and Alzheimer’s diseases. In particular, literature on the putative novel neuroprotective mechanism of the major green tea polyphenol, (-)-epigallocatechin-3-gallate, are examined and discussed in this review.

J Nutr Biochem. 2004 Sep;15(9):506-16

Use of tea extracts (Camelia sinensis) in jelly candies as polyphenols sources in human diet.

Diet rich in polyphenols may be important factor in preventing cardiovascular, neoplastic diseases and slowing down the aging processes. Because tea (Camelia sinensis) is most popular beverage containing relatively large amounts of polyphenols, it could be tremendously important source of polyphenolic constituents in human diet. However, there has been no data on the tea extracts use in particular everyday snacks. Objective of the study was to investigate potential use of tea polyphenol extracts in jelly candies, its taste, colour, consistency and general consumer’s acceptance. Sensory analyses were conducted on two kinds of sweet jellies, with gelatin and agar used as thickening agents. As polyphenol source green and black tea extracts (Camellia sinensis) were used at concentration of 1.0% and 1.5%. Total polyphenol content in jellies ranged between 245.9-1256.5 mg/100g of candies and EGCG (epigallocatechin gallate) strong antioxidant content ranged between 3.2-170.1 mg/100g of candies. Sensory analyses included evaluation of overall appearance, colour, taste, aroma, consistence (homogenicity, clot presence) and clarity of jellies. Comparison of two thickening agents resulted in better properties of gelatin jellies according to its quality: colour, clarity, consistence, taste and aroma (p<0.05). It was found that agar containing jellies were not so clear and aromatic as compared with gelatin (p<0.05). Colour and overall appearance was also much more acceptable by the consumers in gelatin jellies. According to tea extract used it was found that ethanol extracts resulted in lower acceptance for overall acceptance and consistency (p<0.05). Present study indicated that tea polyphenols extracts were accepted by consumers as food product constituents, and might be an interest of wider usage as food components.

Asia Pac J Clin Nutr. 2007;16 Suppl 1:43-6

Green tea consumption and prostate cancer risk in Japanese men: a prospective study.

The incidence of prostate cancer is much lower in Asian than Western populations. Given that environmental factors such as dietary habits may play a major role in the causation of prostate cancer and the high consumption of green tea in Asian populations, this low incidence may be partly due to the effects of green tea. The JPHC Study (Japan Public Health Center-based Prospective Study) was established in 1990 for cohort I and in 1993 for cohort II. The subjects were 49,920 men aged 40-69 years who completed a questionnaire that included their green tea consumption habit at baseline and were followed until the end of 2004. During this time, 404 men were newly diagnosed with prostate cancer, of whom 114 had advanced cases, 271 were localized, and 19 were of an undetermined stage. Green tea was not associated with localized prostate cancer. However, consumption was associated with a dose-dependent decrease in the risk of advanced prostate cancer. The multivariate relative risk was 0.52 (95% confidence interval: 0.28, 0.96) for men drinking 5 or more cups/day compared with less than 1 cup/day (p(trend) = 0.01). Green tea may be associated with a decreased risk of advanced prostate cancer.

Am J Epidemiol. 2008 Jan 1;167(1):71-7

Green tea consumption and mortality due to cardiovascular disease, cancer, and all causes in Japan: the Ohsaki study.

CONTEXT: Green tea polyphenols have been extensively studied as cardiovascular disease and cancer chemopreventive agents in vitro and in animal studies. However, the effects of green tea consumption in humans remain unclear. OBJECTIVE: To investigate the associations between green tea consumption and all-cause and cause-specific mortality. DESIGN, SETTING, AND PARTICIPANTS: The Ohsaki National Health Insurance Cohort Study, a population-based, prospective cohort study initiated in 1994 among 40,530 Japanese adults aged 40 to 79 years without history of stroke, coronary heart disease, or cancer at baseline. Participants were followed up for up to 11 years (1995-2005) for all-cause mortality and for up to 7 years (1995-2001) for cause-specific mortality. MAIN OUTCOME MEASURES: Mortality due to cardiovascular disease, cancer, and all causes. RESULTS: Over 11 years of follow-up (follow-up rate, 86.1%), 4,209 participants died, and over 7 years of follow-up (follow-up rate, 89.6%), 892 participants died of cardiovascular disease and 1,134 participants died of cancer. Green tea consumption was inversely associated with mortality due to all causes and due to cardiovascular disease. The inverse association with all-cause mortality was stronger in women (P = .03 for interaction with sex). In men, the multivariate hazard ratios of mortality due to all causes associated with different green tea consumption frequencies were 1.00 (reference) for less than 1 cup/d, 0.93 (95% confidence interval [CI], 0.83-1.05) for 1 to 2 cups/d, 0.95 (95% CI, 0.85-1.06) for 3 to 4 cups/d, and 0.88 (95% CI, 0.79-0.98) for 5 or more cups/d, respectively (P = .03 for trend). The corresponding data for women were 1.00, 0.98 (95% CI, 0.84-1.15), 0.82 (95% CI, 0.70-0.95), and 0.77 (95% CI, 0.67-0.89), respectively (P<.001 for trend). The inverse association with cardiovascular disease mortality was stronger than that with all-cause mortality. This inverse association was also stronger in women (P = .08 for interaction with sex). In women, the multivariate hazard ratios of cardiovascular disease mortality across increasing green tea consumption categories were 1.00, 0.84 (95% CI, 0.63-1.12), 0.69 (95% CI, 0.52-0.93), and 0.69 (95% CI, 0.53-0.90), respectively (P = .004 for trend). Among the types of cardiovascular disease mortality, the strongest inverse association was observed for stroke mortality. In contrast, the hazard ratios of cancer mortality were not significantly different from 1.00 in all green tea categories compared with the lowest-consumption category. CONCLUSION: Green tea consumption is associated with reduced mortality due to all causes and due to cardiovascular disease but not with reduced mortality due to cancer.

JAMA. 2006 Sep 13;296(10):1255-65

Green tea consumption and cognitive function: a cross-sectional study from the Tsurugaya Project 1.

BACKGROUND: Although considerable experimental and animal evidence shows that green tea may possess potent activities of neuroprotection, neurorescue, and amyloid precursor protein processing that may lead to cognitive enhancement, no human data are available. OBJECTIVE: The objective was to examine the association between green tea consumption and cognitive function in humans. DESIGN: We analyzed cross-sectional data from a community-based Comprehensive Geriatric Assessment (CGA) conducted in 2002. The subjects were 1,003 Japanese subjects aged > or =70 y. They completed a self-administered questionnaire that included questions about the frequency of green tea consumption. We evaluated cognitive function by using the Mini-Mental State Examination with cutoffs of <28, <26, and <24 and calculated multivariate-adjusted odds ratios (ORs) of cognitive impairment. RESULTS: Higher consumption of green tea was associated with a lower prevalence of cognitive impairment. At the <26 cutoff, after adjustment for potential confounders, the ORs for the cognitive impairment associated with different frequencies of green tea consumption were 1.00 (reference) for < or =3 cups/wk, 0.62 (95% CI: 0.33, 1.19) for 4-6 cups/wk or 1 cup/d, and 0.46 (95% CI: 0.30, 0.72) for > or =2 cups/d (P for trend = 0.0006). Corresponding ORs were 1.00 (reference), 0.60 (95% CI: 0.35, 1.02), and 0.87 (95% CI: 0.55, 1.38) (P for trend = 0.33) for black or oolong tea and 1.00 (reference), 1.16 (95% CI: 0.78, 1.73), and 1.03 (95% CI: 0.59, 1.80) (P for trend = 0.70) for coffee. The results were essentially the same at cutoffs of <28 and <24. CONCLUSION: A higher consumption of green tea is associated with a lower prevalence of cognitive impairment in humans.

Am J Clin Nutr. 2006 Feb;83(2):355-61

A green tea extract high in catechins reduces body fat and cardiovascular risks in humans.

OBJECTIVE: The body fat reducing effect and reduction of risks for cardiovascular disease by a green tea extract (GTE) high in catechins was investigated in humans with typical lifestyles. RESEARCH METHODS AND PROCEDURES: Japanese women and men with visceral fat-type obesity were recruited for the trial. After a 2-week diet run-in period, a 12-week double-blind parallel multicenter trial was performed, in which the subjects ingested green tea containing 583 mg of catechins (catechin group) or 96 mg of catechins (control group) per day. Randomization was stratified by gender and body mass index at each medical institution. The subjects were instructed to maintain their usual dietary intake and normal physical activity. RESULTS: Data were analyzed using per-protocol samples of 240 subjects (catechin group; n = 123, control group; n = 117). Decreases in body weight, body mass index, body fat ratio, body fat mass, waist circumference, hip circumference, visceral fat area, and subcutaneous fat area were found to be greater in the catechin group than in the control group. A greater decrease in systolic blood pressure (SBP) was found in the catechin group compared with the control group for subjects whose initial SBP was 130 mm Hg or higher. Low-density lipoprotein (LDL) cholesterol was also decreased to a greater extent in the catechin group. No adverse effect was found. DISCUSSION: The continuous ingestion of a GTE high in catechins led to a reduction in body fat, SBP, and LDL cholesterol, suggesting that the ingestion of such an extract contributes to a decrease in obesity and cardiovascular disease risks.

Obesity (Silver Spring). 2007 Jun;15(6):1473-83

Specific formulation of Camellia sinensis prevents cold and flu symptoms and enhances gamma,delta T cell function: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: Determine if a specific formulation of Camellia sinensis (CSF) can prevent illness and symptoms due to cold and flu, and enhance gammadelta T cell function METHODS: Design: Randomized, double-blind, placebo-controlled study. Subjects: Healthy adults 18-70 years old. Intervention: Proprietary formulation of Camellia sinensis (green tea) capsules, or a placebo, twice a day, for 3 months. Measures of Outcome: As assessed by daily symptom logs, percentage of subjects experiencing cold and flu symptoms, number of days subjects experienced symptoms, and percentage of subjects seeking medical treatment. Mean in vivo and ex vivo proliferative and interferon gamma responses of subjects’ peripheral blood mononuclear cells to gammadelta T cell antigen stimulation. RESULTS: Among subjects taking CSF there were 32.1% fewer subjects with symptoms (P = 0.035), 22.9% fewer overall illnesses of at least 2 days duration (P = 0.092), and 35.6% fewer symptom days (P < 0.002), compared to subjects taking placebo. gammadelta T cells from subjects taking CSF proliferated 28% more (P = 0.017) and secreted 26% more IFN-gamma (P = 0.046) in response to gammadelta T cell antigens, as compared to gammadelta T cells from subjects taking placebo. CSF was well-tolerated. CONCLUSIONS: This proprietary formulation of CSF is a safe and effective dietary supplement for preventing cold and flu symptoms, and for enhancing gammadelta T cell function.

J Am Coll Nutr. 2007 Oct;26(5):445-52