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.[1] Green tea and green tea extracts have been studied in a variety of settings.

Gastrointestinal

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.[6] 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.[7] EGCG is thought to exert its cancer-preventive activity in the bowel by interrupting signalling pathways.[8] 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.[1] 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.[9]

Pancreas

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.[9]

An in vitro study showed that the green tea polyphenol EGCG could prevent pancreatic fibrosis through the antioxidant effect.[1] The same ingredient also showed potential in helping to prevent pancreatitis[2-4] and septic shock[5] 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.[10] 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.[11]

Liver

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.[1] 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.[2] 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.[3]

Prostate

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.[1] 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.[2] 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.[3] Green tea may therefore be of benefit to the general male population.

Haematology

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.[103] 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.[104] 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.[105] 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.[106]

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.[107]

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.[108]

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.[109]

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.[110]

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.[111] Combination treatment of curcumin and EGCG at a constant ratio of 10:1 (EGCG/curcumin) increased death in CLL B cells.[112]

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