Green tea (Camelia sinesis) is of such interest to health researchers as it typically contains 98% green tea polyphenols. Of most interest are the catechins, of which epigallocatechin-3-gallate (EGCG) is the most abundant and well-studied. Polyphenols such as EGCG are metabolised by the bacteria in the gut, which break them down into phenolic acids. These are then absorbed into the blood and excreted in the urine. Green tea and green tea extracts have been studied in a variety of settings.
The anti-cancer benefits of EGCG have not only been shown in the laboratory,[2-5] but in human studies. Consumption of green tea was associated with a 40% reduction in colorectal cancer risk in a cohort of 69,710 Chinese women. In 60,567 non-smoking Chinese men, an intake of at least three cups of green tea a week reduced risk, and each 2g increment of dry green tea leaves per day (roughly the amount of tea in a tea bag) was linked to a 12% reduction in the risk of colorectal cancer. EGCG is thought to exert its cancer-preventive activity in the bowel by interrupting signalling pathways. Anti-inflammatory effects of EGCG in green tea extracts and success in IBD animal trials, a team of researchers tested the concept in humans. The pilot trial showed that patients with mild to moderate ulcerative colitis could reach remission by taking 400 mg or 800 mg of EGCG daily for 56 days. Nineteen patients received more than one dose of EGCG and 53.3% of patients gained remission status, compared to 0% in the placebo group, which didn’t consume any.
Green tea extract contains antioxidant compounds such as epigallocatechin-3-gallate (EGCG). Compounds such as EGCG have been found to have anti-proliferative properties and induce cell death in pancreatic cancer cells, in both in vitro and in vivo studies.[1-4] A study in mice suggests EGCG blocks the pancreatic cancer pathways and it may be useful in both the prevention and treatment of pancreatic cancer.
An in vitro study showed that the green tea polyphenol EGCG could prevent pancreatic fibrosis through the antioxidant effect. The same ingredient also showed potential in helping to prevent pancreatitis[2-4] and septic shock in animal models.
Type 2 Diabetes and Obesity
Studies of EGCG in animals show that it may inhibit the pathways that lead to glucose intolerance caused by obesity[6-9] and may even have a direct anti-obesity effect. In humans, gallated catechin (GC) from the green tea polyphenol EGCG may reduce blood glucose levels through blocking normal glucose uptake in the digestive tract.
Green Tea is well studied and evidence from both in vivo systems and animal models suggests that green tea catechins such as epigallocatechin-3-gallate (EGCG) are likely to prevent fat accumulating in the liver. They do this by decreasing intestinal lipid and carbohydrate absorption, decreasing adipose lipolysis and stimulating hepatic b-oxidation and thermogenesis by improving insulin sensitivity. Catechins are also likely to prevent the progression from liver steatosis to non-alcoholic steatohepatitis (NASH) and then cirrhosis, through their anti-oxidant and anti-inflammatory properties. Green tea polyphenols, especially EGCG, are therefore thought to prevent development of liver cancer.
One study looked at 215 hepatocellular carcinoma (HCC) patients compared to 415 controls. Those who drank green tea for longer than 30 years were at the lowest risk of developing HCC. Other favourable effects reported were possible delayed entry of hepatitis B and C viruses into cells and potential effects on polymorphism of targets for anti-viral therapy. Another clinical trial showed that the daily intake of six green tea polyphenol tablets containing 474 mg of polyphenols significantly reduces oxidative stress in HCC patients.
There is much interest in the use of green tea and EGCG and its potential to decrease progression of disease in the prostate. Mechanisms of the anti-tumour action of green tea include apoptosis and cell cycle arrest via cancer pathways. Both in vivo and in vitro studies have provided convincing evidence of the potential benefits of EGCG from green tea. A recent in vivo study showed that a combination of green tea and quercetin, a methylation inhibitor, can increase prevention of prostate cancer with no side effects. A study of 130 patients with adenocarcinoma of the prostate and 274 non-cancer controls found that the risk of prostate cancer declined with increasing frequency, duration and quantity of green tea consumption. Green tea may therefore be of benefit to the general male population.
95,807 Japanese subjects of the Japan Public Health Center-based Prospective Study completed a questionnaire about their coffee and green tea consumption. Green tea was found not to be linked to lymphoma risk. Clinical trials in lymphoma are lacking using green tea, but one in vitro study found EGCG and trichostatin A (TSA) synergistically reactivate p16(INK4a) gene expression in part through reducing promoter methylation, which may decrease lymphoma CA46 cell proliferation. A previous study found EGCG can activate and up-regulate the expression of p16 gene mRNA which inhibits the proliferation of CA46 cell through inducing the G(0)/G(1) arrest by demethylation and/or by inhibiting DNMT3A and DNMT3B gene. A specific nutrient mixture, containing ascorbic acid, lysine, proline, green tea extract was tested on aggressive forms of NHL including Burkitt’s lymphoma and T-cell lymphoma using Raji and Jurkat cells respectively. The nutrient mixture exhibited anti-proliferative properties at higher concentrations. At 100 mcg/ml and 1000 mcg/ml the mixture completely inhibited Raji cells and Jurkat cells respectively. After the nutrient challenge virtually all Raji and Jurkat cells exposed to 1000 microg/ml were in late apoptosis.
Primary effusion lymphoma (PEL) is a rare form of NHL and is caused by human herpesvirus 8 (HHV8). EGCG was found to induce cell death and ROS generation in PEL cells in a dose-dependent manner in an in-vitro study. The addition of N-acetylcysteine inhibited the EGCG-induced ROS and rescued the cell from EGCG-induced cell death. EGCG also reduced the production of progeny virus from PEL cells without causing HHV8 reactivation.
Green tea extract may benefit patients with early stage CLL. In 2006, Shanafelt and colleagues became aware of four patients with low grade B-cell malignancies who began, on their own initiative, oral ingestion of EGCG containing products and subsequently appeared to have an objective clinical response. Three of these four patients met criteria for partial response by standard response criteria.
In a later phase 2 clinical controlled trial, 42 patients with CLL took 2000mg green tea polyphenols (EGCG) twice a day for 6 months. Green tea polyphenols were well tolerated by patients with CLL and declines in the absolute lymphocyte count and/or lymphadenopathy were observed in the majority of patients.
A recent human clinical controlled trial used green tea extract on 12 patients with stage 0 CLL, and 12 healthy controls. 10 patients completed a 6 month course. Eight out 10 evaluable patients showed a reduction of lymphocytosis and absolute number of circulating T-regulatory cells. One patient had stabilisation of lymphocytosis and a reduction of T-regulatory cells, and 1 patient showed an increase of both lymphocytosis and T-regulatory cells. Only the later patient progressed at 5 months. Both IL-10 and TGF-beta serum levels declined throughout the green tea intake period, in both patients and controls.
When blood was taken from 20 patients with B-cell CLL, ECGC was found to inhibit vascular endothelial growth factor receptor activation and induce apoptosis in primary B CLL B-cells. Combination treatment of curcumin and EGCG at a constant ratio of 10:1 (EGCG/curcumin) increased death in CLL B cells.
- Henning SM, Wang P, Abgaryan N et al. Phenolic acid concentrations in plasma and urine from men consuming green or black tea and potential chemopreventive properties for colon cancer. Mol Nutr Food Res. 2013;57(3):483-93.
- Scalbert A, Manach C, Morand C, et al. Dietary polyphenols and the prevention of diseases. Crit Rev Food Sci Nutr 2005;45:287-306.
- Yang CS. Inhibition of carcinogenesis by tea. Nature 1997;389:134-5.
- Yang CS, Chung JY, Yang GY, et al. Mechanisms of inhibition of carcinogenesis by tea. Biofactors 2000;13:73-9.
- Sánchez-Tena S, Alcarraz-Vizán G, Marín S et al. Epicatechin gallate impairs colon cancer cell metabolic productivity. J Agric Food Chem. 2013 May 8;61(18):4310-7.
- Yang G, Shu XO, Li H, et al. Prospective cohort study of green tea consumption and colorectal cancer risk in women. Cancer Epidemiol Biomarkers Prev 2007;16:1219-23.
- Yang G, Zheng W, Xiang YB et al. Green tea consumption and colorectal cancer risk: a report from the Shanghai Men’s Health Study. Carcinogenesis. 2011;32(11):1684-8.
- Oh S, Gwak J, Park S et al. Green tea polyphenol EGCG suppresses Wnt/β-catenin signaling by promoting GSK-3β- and PP2A-independent β-catenin phosphorylation/degradation. Biofactors. 2014 Nov-Dec;40(6):586-95.
- Dryden GW, Lam A, Beatty K et al. A pilot study to evaluate the safety and efficacy of an oral dose of (-)-epigallocatechin-3-gallate-rich polyphenon E in patients with mild to moderate ulcerative colitis. Inflamm Bowel Dis. 2013;19(9):1904-12.
- Vu, HA, Beppu Y, Chi HT et al. Green tea epigallocatechin gallate exhibits anticancer effect in human pancreatic carcinoma cells via the inhibition of both focal adhesion kinase and insulin-like growth factor-I receptor. J Biomed Biotechnol 2010: 290516.
- Shankar, S, Suthakar G, Srivastava RK. et al. Epigallocatechin-3-gallate inhibits cell cycle and induces apoptosis in pancreatic cancer. Front Biosci 2007;12:5039-5051.
- Shankar, S, Ganapathy S, et al. EGCG inhibits growth, invasion, angiogenesis and metastasis of pancreatic cancer. Front Biosci 2008;13:440-452.
- Li, Y, Zhang T, Jiang Y, et al. (-)-Epigallocatechin-3-gallate inhibits Hsp90 function by impairing Hsp90 association with cochaperones in pancreatic cancer cell line Mia Paca-2. Mol Pharm 2009;6(4):1152-1159.
- Shankar S, Marsh L, Srivastava RK. EGCG inhibits growth of human pancreatic tumors orthotopically implanted in Balb C nude mice through modulation of FKHRL1/FOXO3a and neuropilin. Mol Cell Biochem. 2013;372(1-2):83-94.
- Asaumi H, Watanabe S, Taguchi M et al. Green tea polyphenol (-)-epigallocatechin-3-gallate inhibits ethanol-induced activation of pancreatic stellate cells. Eur J Clin Invest. 2006;36(2):113-22.
- Takabayashi F, Harada N, Hara Y. The effects of green tea catechins (Polyphenon) on DL-ethionine-induce acute pancreatitis. Pancreas. 1995;11(2):127-31.
- Takabayashi F, Harada N. Effects of green tea catechins (Polyphenon 100) on cerulein-induced acute pancreatitis in rats. Pancreas. 1997;14(3):276-9.
- Babu BI, Malleo G, Genovese T et al. Green tea polyphenols ameliorate pancreatic injury in cerulein-induced murine acute pancreatitis. Pancreas. 2009;38(8):954-67.
- Di Paola R, Mazzon E, Muià C. Green tea polyphenol extract attenuates zymosan-induced non-septic shock in mice. Shock. 2006;26(4):402-9.
- Furuyashiki T, Nagayasu H, Aoki Y, et al. Tea catechin suppresses adipocyte differentiation accompanied by down-regulation of PPARgamma2 and C/EBPalpha in 3T3-L1 cells. Biosci Biotechnol Biochem. 2004;68:2353–2359.
- Klaus S, Pultz S, Thone-Reineke C, Wolfram S. Epigallocatechin gallate attenuates diet-induced obesity in mice by decreasing energy absorption and increasing fat oxidation. Int J Obes (Lond) 2005;29:615–623.
- Wu LY, Juan CC, Hwang LS, Hsu YP, Ho PH, Ho LT. Green tea supplementation ameliorates insulin resistance and increases glucose transporter IV content in a fructose-fed rat model. Eur J Nutr. 2004;43:116–124.
- Han MK. Epigallocatechin gallate, a constituent of green tea, suppresses cytokine-induced pancreatic beta-cell damage. Exp Mol Med. 2003;35:136–139. [
- Tian C, Ye X, Zhang R, Long J, Ren W, Ding S, Liao D, Jin X, Wu H, Xu S, Ying C. Green tea polyphenols reduced fat deposits in high fat-fed rats via erk1/2-PPARgamma-adiponectin pathway. PLoS One. 2013;8:e53796.
- Park JH, Jin JY, Baek WK, Park SH, Sung HY, Kim YK, Lee J, Song DK. Ambivalent role of gallated catechins in glucose tolerance in humans: a novel insight into non-absorbable gallated catechin-derived inhibitors of glucose absorption. J Physiol Pharmacol. 2009;60:101–109.
- C. Masterjohn, Bruno S. The therapeutic potential of green tea in Non-alcoholic fatty liver disease. Nutrition reviews, 2012;70(1):41-56.
- Li Y, Chang SC, Goldstein BY et al. Green tea consumption, inflammation and the risk of primary hepatocellular carcinoma in a Chinese population Cancer Epidemiol. 2011;35(4):362-8.
- Baba Y, Sonoda JI, Hayashi S et al. Reduction of oxidative stress in liver cancer patients by oral green tea polyphenol tablets during hepatic arterial infusion chemotherapy. Exp Ther Med. 2012;4(3):452-458.
- Johnson JJ, Bailey HH, Mukhtar H. Green tea polyphenols for prostate cancer chemoprevention: a translational perspective. Phytomedicine 2010; 17: 3–13.
- Wang P, Vadgama JV, Said JW, Magyar CE, Doan N, Heber D, Henning SM. Enhanced inhibition of prostate cancer xenograft tumor growth by combining quercetin and green tea. J Nutr Biochem. 2014;2:73-80.
- Jian L, Xie LP, Lee AH, Binns CW. Protective effect of green tea against Prostate Cancer: a case-control study in southeast China. Int J Cancer. 2004;108:130–135.
- Ugai T, Matsuo K, Sawada N, Iwasaki M, Yamaji T et al.: Coffee and Green Tea Consumption and Subsequent Risk of Malignant Lymphoma and Multiple Myeloma in Japan: The Japan Public Health Center-based Prospective Study. Cancer Epidemiol Biomarkers Prev 26, 1352-1356, 2017. doi: 10.1158/1055-9965.EPI-17-0231. [PUBMED]
- Wu DS, Shen JZ, Yu AF, Fu HY, Zhou HR, et al.: Epigallocatechin-3-gallate and trichostatin A synergistically inhibit human lymphoma cell proliferation through epigenetic modification of p16INK4a. Oncol Rep 30, 2969-75, 2013.doi: 10.3892/or.2013.2734 [PUBMED]
- Yu AF, Shen JZ, Chen ZZ, Fan LP, Lin FA.: [Demethylation and transcription of p16 gene in malignant lymphoma cell line CA46 induced by EGCG]. Zhongguo Shi Yan Xue Ye Xue Za Zhi (abstr) 16, 1073-1078, 2008. [PUBMED]
- Roomi MW, Bhanap BA, Roomi NW, Rath M, Niedzwiecki A.: Antineoplastic effects of nutrient mixture on raji and jurkat t cells: the two highly aggressive non Hodgkin’s lymphoma cell lines. Exp Oncol 31, 149-55, 2009. [PUBMED]
- Tsai C-Y, Chen C-Y, Chiou Y-H, Shyu HW, Lin KH et al.: Epigallocatechin-3-Gallate Suppresses Human Herpesvirus 8 Replication and Induces ROS Leading to Apoptosis and Autophagy in Primary Effusion Lymphoma Cells. Int J Mol Sci 19, 16, 2017. doi: 10.3390/ijms19010016. [PUBMED]
- Shanafelt TD, Lee YK, Call TG, Nowakowski GS, Dingli D et al.: Clinical effects of oral green tea extracts in four patients with low grade B-cell malignancies. Leuk Res 30, 707-12, 2006. doi 10.1016/j.leukres.2005.10. [PUBMED]
- Shanafelt TD, Call TG, Zent CS Leis JF, LaPlant B et al.: Phase 2 trial of daily, oral Polyphenon E in patients with asymptomatic, Rai stage 0 to II chronic lymphocytic leukemia. Cancer 119, 363-70, 2013. doi: 10.1002/cncr.27719. [PUBMED]
- D’Arena G, Simeon V, De Martino L, Statuto T, D’Auria F et al.: Regulatory T-cell modulation by green tea in chronic lymphocytic leukemia. Int J Immunopathol Pharmacol 26, 117-25, 2013. doi: 10.1177/039463201302600111 [PUBMED]
- Lee YK, Bone ND, Strege AK Shanafelt TD, Jelinek DF et al.: VEGF receptor phosphorylation status and apoptosis is modulated by a green tea component, epigallocatechin-3-gallate (EGCG), in B-cell chronic lymphocytic leukemia. Blood 104, 788–94, 2004. doi: 10.1182/blood-2003-08-2763 [PUBMED]
- Ghosh AK, Kay NE, Secreto CR, Shanafelt TD: Curcumin inhibits prosurvival pathways in chronic lymphocytic leukemia B cells and may overcome their stromal protection in combination with EGCG. Clin Cancer Res 15, 1250-8, 2009. doi: 10.1158/1078-0432.CCR-08-1511. [PUBMED]