Greenteahaus:  The Green Tea Reference Library

Green tea is anti-thrombotic and may help blood circulation

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1 Cholesterol-lowering effect of a theaflavin-enriched green tea extract: a randomized controlled trial. Arch Intern Med. 2003 Jun 23;163(12):1448-53.
2 Effect of green tea polyphenols on the genes with atherosclerotic potential. Phytother Res. 2004 Feb;18(2):177-9.
3 Green tea consumption and serum lipids and lipoproteins in a population of healthy workers in Japan. Ann Epidemiol. 2002 Apr;12(3):157-65.
4 Effects of green tea intake on the development of coronary artery disease. Circ J. 2004 Jul;68(7):665-70.
5 Green and black teas inhibit atherosclerosis by lipid, antioxidant, and fibrinolytic mechanisms. J Agric Food Chem. 2004 Jun 2;52(11):3661-5.
6 Effect of drinking green tea on age-associated accumulation of Maillard-type fluorescence and carbonyl groups in rat aortic and skin collagen. Arch Biochem Biophys. 2002 Jan 15;397(2):424-9.
7 Green tea is a “blood thinner” by inhibiting oxidation of arachidonic and linoleic acids. J Agric Food Chem. 2004 Jul 28;52(15):4860-4.
8 The antiplatelet activities of green tea prevent death in mice due to pulmonary thrombosis. Thromb Res. 1999 Nov 1;96(3):229-37.
9 Antiplatelet function of green tea is mediated by inhibition of thrombin proteolytic activity and tyrosine kinases Syk and Lyn. Thromb Haemost. 2003 May;89(5):866-74.
10 Green tea catechins administered orally into rats inhibited platelet aggregation induced by arachidonic acid. Prostaglandins Leukot Essent Fatty Acids. 2004 Jul;71(1):25-31.
11 Antiplatelet activity of green tea catechins may be mediated by inhibition of cytoplasmic calcium increase induced by thrombin treatment. J Cardiovasc Pharmacol. 2001 Dec;38(6):875-84.

Abstracts
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1

Maron DJ, Lu GP, Cai NS, Wu ZG, Li YH, Chen H, Zhu JQ, Jin XJ, Wouters BC, Zhao J. Cholesterol-lowering effect of a theaflavin-enriched green tea extract: a randomized controlled trial. Arch Intern Med. 2003 Jun 23;163(12):1448-53.

BACKGROUND: Tea consumption has been associated with decreased cardiovascular risk, but potential mechanisms of benefit are ill-defined. While epidemiologic studies suggest that drinking multiple cups of tea per day lowers low-density lipoprotein cholesterol (LDL-C), previous trials of tea drinking and administration of green tea extract have failed to show any impact on lipids and lipoproteins in humans. Our objective was to study the impact of a theaflavin-enriched green tea extract on the lipids and lipoproteins of subjects with mild to moderate hypercholesterolemia. METHODS: Double-blind, randomized, placebo-controlled, parallel-group trial set in outpatient clinics in 6 urban hospitals in China. A total of 240 men and women 18 years or older on a low-fat diet with mild to moderate hypercholesterolemia were randomly assigned to receive a daily capsule containing theaflavin-enriched green tea extract (375 mg) or placebo for 12 weeks. Main outcome measures were mean percentage changes in total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglyceride levels compared with baseline. RESULTS: After 12 weeks, the mean +/- SEM changes from baseline in total cholesterol, LDL-C, HDL-C, and triglyceride levels were -11.3% +/- 0.9% (P =.01), -16.4% +/- 1.1% (P =.01), 2.3% +/- 2.1% (P =.27), and 2.6% +/- 3.5% (P =.47), respectively, in the tea extract group. The mean levels of total cholesterol, LDL-C, HDL-C, and triglycerides did not change significantly in the placebo group. No significant adverse events were observed. CONCLUSION: The theaflavin-enriched green tea extract we studied is an effective adjunct to a low-saturated-fat diet to reduce LDL-C in hypercholesterolemic adults and is well tolerated.
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2 Kaul D, Sikand K, Shukla AR. Effect of green tea polyphenols on the genes with atherosclerotic potential. Phytother Res. 2004 Feb;18(2):177-9.

The genomics of atherosclerosis can arise as a result of cross-talk between the genes coding for the LDL-receptor (LDL-R), LXR-alpha, PPARs (alpha, gamma), CD36 and C-myc because these genes control lipid metabolism, cytokine production and cellular activity within the arterial wall. The effect of green tea polyphenols (GTPs) upon such genomics revealed their ability to down-regulate genes coding for PPAR-gamma, CD36, LXR-alpha, C-myc coupled with up-regulation of genes coding for LDL-R and PPAR-alpha at the transcriptional level. Based upon these results, it is proposed that GTPs have the inherent capacity to inhibit the development of atherosclerotic lesions.
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3 Tokunaga S, White IR, Frost C, Tanaka K, Kono S, Tokudome S, Akamatsu T, Moriyama T, Zakouji H. Green tea consumption and serum lipids and lipoproteins in a population of healthy workers in Japan. Ann Epidemiol. 2002 Apr;12(3):157-65.

 PURPOSE: To examine the relation between green tea consumption and serum lipids and lipoproteins. METHODS: The subjects were 13,916 workers (8476 men and 5440 women) aged 40-69 years at over 1000 workplaces in Nagano prefecture, central Japan. They underwent health screening offered by a single medical institute between April 1995 and March 1996 and did not have morbid conditions affecting serum cholesterol levels. Serum concentrations of total cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides were measured at the screening. The consumption of green tea and other life-style characteristics were ascertained by a questionnaire. The data were analyzed with multivariate linear model. RESULTS: Daily consumption of green tea was reported by 86.7% of subjects. Green tea consumption was, statistically, significantly associated with lower levels of serum total cholesterol in both men and women while its associations with serum triglycerides and HDL cholesterol were not statistically significant. The inverse association of serum total cholesterol with green tea consumption appeared to level off at the consumption of more than 10 cups/day. Excluding the outlying subjects drinking more than 10 cups/day (0.4%), the regression analysis adjusting for age, body mass index, ethanol intake, smoking habit, coffee intake, and type of work showed that daily consumption of one cup of green tea was associated with a reduction in serum total cholesterol by 0.015 mmol/L (95% confidence interval 0.006 to 0.024, p < 0.001) in men and 0.015 mmol/L (0.004 to 0.025, p < 0.01) in women. After additional adjustment for selected dietary factors, the inverse association remained statistically significant; one cup of green tea per day was associated with a reduction in serum total cholesterol by 0.010 mmol/L (0.001 to 0.019, p = 0.03) in men and 0.012 mmol/L (0.001 to 0.022, p = 0.03) in women. CONCLUSION: Consumption of green tea was associated with lower serum concentration of total cholesterol in Japanese healthy workers age 40-69 years; however, green tea consumption was unrelated to serum HDL-cholesterol and triglycerides.
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4 Sano J, Inami S, Seimiya K, Ohba T, Sakai S, Takano T, Mizuno K. Effects of green tea intake on the development of coronary artery disease. Circ J. 2004 Jul;68(7):665-70.

BACKGROUND: Green tea, a popular beverage in Japan, contains many polyphenolic antioxidants, which might prevent atherosclerosis. This study was designed to determine whether the consumption of green tea is proportionately associated with a decreased incidence of coronary artery disease (CAD) and the cardiovascular and cerebrovascular prognosis. METHODS AND RESULTS: The study group comprised 203 patients who underwent coronary angiography (109 patients with significant coronary stenosis and 94 patients without). Predictors for CAD were analyzed and the patients' cardiovascular and cerebrovascular events were followed. Green tea consumption was significantly higher in patients without CAD than in those with CAD (5.9+/-0.5 vs 3.5+/-0.3 cups/day; p<0.001). An inverse relationship between the intake of green tea and the incidence of CAD was observed (p<0.001). The green tea intake per day was an independent predictor for CAD based on a multivariate logistic regression analysis (odds ratio: 0.84 and 95% confidence interval: 0.76-0.91). In contrast, the green tea intake was not a predictor of cardiovascular and cerebrovascular events based on the Cox proportional hazard model. CONCLUSIONS: Green tea consumption was associated with a lower incidence of CAD in the present study population in Japan. Therefore, the more green tea patients consume, the less likely they are to have CAD.
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5 Vinson JA, Teufel K, Wu N. Green and black teas inhibit atherosclerosis by lipid, antioxidant, and fibrinolytic mechanisms. J Agric Food Chem. 2004 Jun 2;52(11):3661-5.

Tea is the most widely consumed beverage in the world, second only to water. Most laypersons and scientists believe that green tea is healthier than black tea due to the low incidence of heart disease and cancer in the Orient. Here, we report the first dose-response comparison of a green and black tea on normal hamsters after long-term supplementation and on a hamster model of atherosclerosis. Both teas were equally effective in inhibiting atherosclerosis with the lower dose decreasing it 26-46% and the high dose decreasing it 48-63%. Atherosclerosis was inhibited by three mechanisms: hypolipemic, antioxidant, and antifibrinolytic. There was a significant correlation between atherosclerosis and the three mechanisms. In the normal animals, teas also caused some improvement in plasma low density lipoprotein (LDL), LDL/high density lipoprotein ratio, triglycerides, lipid peroxides, lower density lipoprotein lipid peroxides, and fibrinogen. Isolated lower density lipoprotein oxidizability was also reduced in all groups. Green and black teas were equally effective at human equivalent doses, thus confirming human intervention and epidemiology studies and providing mechanisms for teas' benefit.
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6 Song DU, Jung YD, Chay KO, Chung MA, Lee KH, Yang SY, Shin BA, Ahn BW. Effect of drinking green tea on age-associated accumulation of Maillard-type fluorescence and carbonyl groups in rat aortic and skin collagen. Arch Biochem Biophys. 2002 Jan 15;397(2):424-9.

Tea catechins and other flavonoids have been shown to potentially protect against chronic cardiovascular diseases such as coronary heart disease and atherosclerosis. In this study, 6-month-old female Sprague-Dawley rats were fed green tea extract (50 mg/100 ml in drinking water) up to the age of 22 months, and the age-associated changes in Maillard-type fluorescence and carbonyl groups in the aortic and skin collagen were compared with those occurring in the water-fed control animals. Collagen-linked Maillard-type fluorescence was found to increase in both the aortic and skin tissues as animals aged. The age-associated increase in the fluorescence in the aortic collagen was remarkably inhibited by the green tea extract treatment, while that occurring in the skin collagen was not significantly inhibited by the treatment. The collagen carbonyl content also increased in both the aortic and skin tissues as animals aged. In contrast with the case of Maillard-type fluorescence, however, the age-associated increase in the carbonyl content was not inhibited by the green tea extract treatment either in the aortic or skin collagen. These results suggest that the inhibition of AGE formation in collagen is an important mechanism for the protective effects of tea catechins against cardiovascular diseases.
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7 Liu YJ, Pan BS. Inhibition of fish gill lipoxygenase and blood thinning effects of green tea extract. J Agric Food Chem. 2004 Jul 28;52(15):4860-4.

The objective of the present study was to determine whether green tea extracts are inhibitory to lipid oxidations catalyzed by lipoxygenase (LOX) and hemoglobin (Hb) using fish as an animal model. Green tea was extracted with water. LOX was extracted from the gills of grey mullet and tilapia, respectively. The LOX activity was determined using chemiluminescence and high-pressure liquid chromatography. The green tea extract showed inhibitory effects on both LOX-catalyzed and Hb-catalyzed oxidation of arachidonic acid and linoleic acid. Blood thinning effects were observed ex vivo by mixing the green tea extract with fish red blood cells and showed that the flow behavior of fish blood becomes closer to the Newtonian type with a thinner consistency. Similar effects were found on tilapia and grey mullet.
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8 Kang WS, Lim IH, Yuk DY, Chung KH, Park JB, Yoo HS, Yun YP. Antithrombotic activities of green tea catechins and (-)-epigallocatechin gallate. Thromb Res. 1999 Nov 1;96(3):229-37.

The antithrombotic activities and mode of action of green tea catechins (GTC) and (-)-epigallocatechin gallate (EGCG), a major compound of GTC, were investigated. Effects of GTC and EGCG on the murine pulmonary thrombosis in vivo, human platelet aggregation in vitro, and ex vivo, and coagulation parameters were examined. GTC and EGCG prevented death caused by pulmonary thrombosis in mice in vivo in a dose-dependent manner. They significantly prolonged the mouse tail bleeding time of conscious mice. They inhibited adenosine diphosphate- and collagen-induced rat platelet aggregation ex vivo in a dose-dependent manner. GTC and EGCG inhibited ADP-, collagen-, epinephrine-, and calcium ionophore A23187-induced human platelet aggregation in vitro dose dependently. However, they did not change the coagulation parameters such as activated partial thromboplastin time, prothrombin time, and thrombin time using human citrated plasma. These results suggest that GTC and EGCG have the antithrombotic activities and the modes of antithrombotic action may be due to the antiplatelet activities, but not to anticoagulation activities.
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9 Deana R, Turetta L, Donella-Deana A, Dona M, Brunati AM, De Michiel L, Garbisa S. Green tea epigallocatechin-3-gallate inhibits platelet signalling pathways triggered by both proteolytic and non-proteolytic agonists. Thromb Haemost. 2003 May;89(5):866-74.

Epigallocatechin-3-gallate (EGCG), a component of green tea, inhibits human platelet aggregation and cytosolic [Ca(2+)](c) increases more strongly when these processes are induced by thrombin than by the non-proteolytic thrombin receptor activating peptide (TRAP), thromboxane mimetic U46619, or fluoroaluminate. In line with the previously demonstrated EGCG anti-proteolytic activity, a marked inhibition on aggregation is obtained by pre-incubation of thrombin with EGCG prior to addition to cellular suspension. The catechin also reduces cellular Ca(2+) influx following thapsigargin-induced calcium emptying of endoplasmic reticulum, and the agonist-promoted cellular protein tyrosine phosphorylation. Both tyrosine kinases Syk and Lyn, immuno-precipitated from stimulated platelets, are greatly inhibited upon cellular pre-incubation with EGCG, which also inhibits the in vitro auto-phosphorylation and exogenous activity of these two enzymes purified from rat spleen. Both thrombin-induced aggregation and [Ca(2+)](c) increase are reduced in platelets from rats that drank green tea solutions. It is concluded that EGCG inhibits platelet activation, by hindering the thrombin proteolytic activity, and by reducing the agonist-induced [Ca(2+)](c) increase through inhibition of Syk and Lyn activities.
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10 Son DJ, Cho MR, Jin YR, Kim SY, Park YH, Lee SH, Akiba S, Sato T, Yun YP. Antiplatelet effect of green tea catechins: a possible mechanism through arachidonic acid pathway. Prostaglandins Leukot Essent Fatty Acids. 2004 Jul;71(1):25-31.

We have previously reported that green tea catechins (GTC) showed an antithrombotic activity, which might be due to antiplatelet effect rather than anticoagulation. The present study was performed to investigate the effect of GTC on the arachidonic acid (AA) metabolism in order to elucidate a possible antiplatelet mechanism. GTC inhibited the collagen-, AA- and U46619-induced rabbit platelet aggregation in vitro in a concentration-dependent manner, with IC50 values of 61.0+/-2.5, 105.0+/-4.9 and 67.0+/-3.2 microg/ml, respectively. Moreover, GTC administered orally into rats inhibited the AA-induced platelet aggregation ex vivo by 46.9+/-6.1% and 95.4+/-2.2% at the doses of 25 and 50 mg/kg, respectively. [3H]AA liberation induced by collagen in [3H]AA incorporated rabbit platelets was significantly suppressed by GTC compared to the control. GTC also significantly inhibited the thromboxane A2 (TXA2) and prostaglandin D2 (PGD2) generations induced by addition of AA in intact rabbit platelets. GTC significantly inhibited TXA2 synthase activity in a concentration-dependent manner. Moreover, adenosine triphosphate (ATP) release from dense granule was inhibited by GTC in washed platelets. These results suggest that the antiplatelet activity of GTC may be due to the inhibition of TXA2 formation through the inhibition of AA liberation and TXA2 synthase.
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11 Kang WS, Chung KH, Chung JH, Lee JY, Park JB, Zhang YH, Yoo HS, Yun YP. Antiplatelet activity of green tea catechins is mediated by inhibition of cytoplasmic calcium increase. J Cardiovasc Pharmacol. 2001 Dec;38(6):875-84.

We have previously reported that green tea catechins (GTC) display a potent antithrombotic activity, which might be due to antiplatelet rather than anticoagulation effects. In the current study, we investigated the antiplatelet mechanism of GTC. We tested the effects of GTC on the aggregation of human platelets and on the binding of fluorescein isothiocyanate-conjugated fibrinogen to human platelet glycoprotein (GP) IIb/IIIa. GTC inhibited the collagen-, thrombin-, adenosine diphosphate (ADP)-, and calcium ionophore A23187-induced aggregation of washed human platelets, with 50% inhibitory concentration values of 0.64, 0.52, 0.63, and 0.45 mg/ml, respectively. GTC significantly inhibited fibrinogen binding to human platelet surface GPIIb/IIIa complex but failed to inhibit binding to purified GPIIb/IIIa complex. These results indicate that the antiplatelet activity of GTC may be due to inhibition of an intracellular pathway preceding GPIIb/IIIa complex exposure. We also investigated the effects of GTC on intracellular calcium levels, which are critical in determining the activation status of platelets and on induction of platelet aggregation by thapsigargin, which is a selective inhibitor of the Ca(2+)-ATPase pump. Pretreatment of human platelets with GTC significantly inhibited the rise in intracellular Ca(2+) concentration induced by thrombin treatment, and GTC significantly inhibited the thapsigargin-induced platelet aggregation. We also examined the effect of GTC on the second messenger, inositol 1,4,5-triphosphate (IP(3)). GTC significantly inhibited the phosphoinositide breakdown induced by thrombin. Taken together, these observations suggest that the antiplatelet activity of GTC is be mediated by inhibition of cytoplasmic calcium increase, which leads to the inhibition of fibrinogen-GPIIb/IIIa binding via the activation of Ca(2+)-ATPase and inhibition of IP(3) formation.
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