

Chinese tea, green tea extract, green tea polyphenols, epigallocatechin gallate (EGCG)
Green tea is a common beverage consumed in Asia. In recent years, green tea and its extracts have been used to prevent and treat hyperlipidemia, hypertension, atherosclerosis and cancer. The active constituent is epigallocatechin-3-gallate (EGCG), which accounts for 40% of the total polyphenol content of green tea extract. Studies of chemopreventive activity of green tea indicated positive results (1) (2) (3) (4) (5) (41). However, a meta analysis found no such benefits of green tea for prevention of gastric cancer (42). The FDA has concluded that green tea is unlikely to reduce the risk of cancers (6). EGCG has been shown to modulate vascular endothelial growth factor (VEGF) leading to apoptosis in leukemic cells (7)and research evaluating the effectiveness of green tea extracts to treat cancer is currently underway. Theaflavin-enriched green tea extract can be used to lower low-density lipoprotein cholesterol (LDL-C) (8).
Regular consumption of green tea may reduce the risk of hypertension (9) and positively affect mood (10), but while it may enhance glucose tolerance in healthy individuals (11) (12), it did not improve insulin sensitivity or glycemic control in overweight or obese males (10) or in individuals with type II diabetes (13). Green tea may also reduce mortality due to cardiovascular disease in both men and women (14). Topical application of green tea extracts effectively treats external genital and perianal warts (15) (16) (17). A green tea extract, sinecatechin, is an FDA approved drug.
Caffeinated green tea may cause insomnia and nausea. Use of decaffeinated products may be preferred due to lower incidence of adverse events, but data are inconsistent regarding the relative efficacy of caffeinated versus decaffeinated teas. Tannins in green tea may reduce absorption and bioavailability of codeine, atropine, and iron supplements (18). The polyphenolic constituents in green tea can negate the therapeutic effect of bortezomib, an anticancer drug (37). Patients undergoing chemotherapy should avoid consuming green tea products.
Animal studies indicate that oral consumption of green tea extract during fasting can increase the risk of toxicity (49). Human studies are warranted.
Green tea
The anticancer activity of green tea is thought to be related to its polyphenol content. Its chemopreventive attributes are associated with catechin epigallocatechin-3-gallate (EGCG), which is thought to induce apoptosis and tumor antiangiogenesis (20). EGCG may inhibit enzymes involved in cell replication and DNA synthesis by interfering with cell-to-cell adhesion or via inhibition of intracellular communication pathways required for cell division (21). In vitro data indicate that concentrations of 30 mcg/mL EGCG and (-)-epigallocatechin (EGC) inhibit lipoxygenase-dependent arachidonic acid metabolism by 30-75% in normal human colon mucosa and colon cancers (22). Other studies in human colon cancer cell lines suggest that EGCG inhibits topoisomerase I, but not topoisomerase II (23). EGCG also inhibits DNA replication in vitro in leukemia cancer cell lines (24). EGCG has been shown to modulate vascular endothelial growth factor (VEGF) leading to apoptosis in leukemic cells (7). Topical EGCG may be useful as chemoprevention for skin cancer, but additional research and formulation are necessary (3).
Green tea’s antioxidant activity may repair oxidative damage to cells, but its role in protection against cancer is unclear. Mechanism of action is not fully known, as the polyphenols may act synergistically with other constituents of the plant. Administration of green tea inhibits UVB light-induced carcinogenesis (25), and when given before and during carcinogen treatment, reduces the incidence and number of stomach and esophageal tumors in mice (26).
The mechanism by which green tea influences blood pressure is thought to be mediated through EGCG’s modulation of vascular constriction. EGCG induces nitric oxide (NO) production through the activation of endothelial NO synthase, resulting in vasodilation (27).
The tannins in green tea may have antibacterial properties (28) and can produce anti-diarrheal effects. Green tea is thought to confer cardiovascular protection by increasing HDL cholesterol, decreasing LDL cholesterol and triglycerides (8) (29), as well as by blocking platelet aggregation. Flavonoids present in green tea may reduce lipoprotein oxidation (30). Green tea also contains caffeine, which has stimulatory effects and is responsible for the majority of adverse effects and drug interactions. It is unknown whether removing caffeine alters green tea’s activities (25).
Catechins from green tea are absorbed rapidly; the addition of milk does not impair bioavailability of tea catechins in green tea (31). Following ingestion of steeped green tea leaves or catechin extract, polyphenol can be measured in blood, urine, saliva, and feces (19) (26) (32) (33). This indicates that ingested polyphenols and their metabolites may provide localized tissue action in addition to indirect gastrointestinal effects.
Although the U.S. Food and Drug Administration (FDA) includes tea on their list of “Generally Recognized As Safe” substances, pregnant women and women who breast feed should limit their intake of green tea because of caffeine content.
Because tea can pass into breast milk, it may cause sleep disorders in nursing infants. Green tea ingestion in infants has been linked to impaired iron metabolism and microcytic anemia.
Individuals with peptic ulcers may want to avoid drinking green tea because it can stimulate the production of gastric acid. (29)
Caffeine in green tea may increase PT / PTT.
Pisters KM, et al. Phase I trial of oral green tea extract in adult patients with solid tumors. J Clin Oncol 2001;19:1830-8.
A phase I trial to determine the maximum-tolerated dose, toxicity, and pharmacology of oral green tea extract (GTE) administered once or three times daily to patients with refractory solid tumors. Each cohort consisted of three or more adult cancer patients with dose ranges of 0.5 to 5.05 g/m2 once daily and 1.0 to 2.2 grams/m2 three times daily with water after meals for 4 weeks, to a maximum of 6 months. Pharmacokinetic analyses were encouraged but optional. A total of 49 patients were studied. Patient characteristics: median age, 57 years (range, 27 to 77 years); 23 patients were women (47%); 21 were diagnosed with non-small-cell lung, 19 with head and neck cancer, three with mesothelioma, and six had other cancers. No major responses were noted. Mild to moderate toxicity was related to caffeine content of GTE and promptly reversed upon discontinuation. Dose-limiting toxicities included neurologic and gastrointestinal effects. The maximum-tolerated dose was 4.2 g/m2 once daily or 1.0 g/m2 three times daily (approximately 2.5 liters brewed green tea/day). Additional studies are recommended.
Tsubono Y, et al. Green tea and the risk of gastric cancer in Japan. N Engl J Med 2001;344:632-6.
A prospective population survey conducted in the Miyagi Prefecture of Japan assessing green tea intake and various health habits. A total of 26,311 resident surveys were included equaling nearly 200,000 person-years of follow-up. No association was found between consumption of green tea (range <1 to >5 cups per day) and risk of gastric cancer development. Adjustments were made for cigarette and alcohol use, age, health insurance, and other dietary intake. While results cannot be extrapolated to other populations, it appears that green tea is not related to an increase or decrease in risk of gastric cancer.
Maron D, et al. Cholesterol-lowering effect of a theaflavin-enriched green tea extract: a randomized controlled trial. Arch Intern Med. 2003 Jun 23;163(12):1448-53.
In this double-blind, randomized, placebo-controlled trial, 240 adults were given either theaflavin-enriched green tea extract in form of 375mg capsule daily or a placebo. After 12 weeks, patients in the tea extract group have significantly less low-density lipoprotein cholesterol (LDL-C) and total cholesterol (16.4% and 11.3% lower than baseline, p<0.01) then the placebo group. The author concluded that theaflavin-enriched green tea extract can be used together other dietary approaches to reduce LDL-C.
Kuriyama S, Shimazu T, Ohmori K, et al. Green tea consumption and mortality due to cardiovascular disease, cancer, and all causes in Japan: the Ohsaki study. JAMA. 2006;296(10):1255-65.
This is a prospective study initiated in 1994 in Japan involving 40,530 adults, aged 40-79 years. The subjects did not have stroke, coronary heart disease, or cancer at baseline. They were followed for 11 years for deaths due to all causes and for seven years for cause-specific mortality. Researchers observed an inverse relationship between green tea consumption and deaths due to cardiovascular disease and other causes in both men and women. However, no such association was found for decrease in the number of deaths due to cancer.
Although the sample size of the study is large, the number of cardiovascular disease and cancer cases was small therefore, the statistical power may not be sufficient. Other limitations of the study include patients lost to follow-up and obtaining data from self-administered questionnaires that may not be accurate. Therefore, well-designed clinical trials are needed to confirm the protective effects of green tea.
Bottom Line: Green tea may help to lower cholesterol. Studies of its anticancer effects are underway.
Green tea contains substances called polyphenols, which scientists think contribute to its anti-cancer activity. Laboratory studies of one polyphenol, catechin epigallocatechin-3-gallate (EGCG), show that it may interfere with several of the processes involved in cell replication, causing tumor cell death (apoptosis). It also might slow the formation of blood vessels around tumors. Epigallocatechin (ECG), another polyphenol, stops leukemic cells from multiplying in laboratory studies. As a proven antioxidant, green tea may repair cell damage, but whether it can prevent cancer is uncertain. Tannins like those found in green tea generally have antibacterial properties. It is unknown how green tea might help protect the heart, but it reduces LDL (“bad”) cholesterol and increases HDL (“good”) cholesterol. Scientists also do not know whether removing caffeine from green tea will remove its possible anti-cancer effects.
Animal studies indicate that oral consumption of green tea extract during fasting can increase the risk of toxicity. Human studies are needed.
Cancer treatment:
A phase I trial studied 49 patients with solid tumors who had not responded to any other treatments in order to find the optimum dose of green tea extract. Patients were given various doses of the extract for six months. None of the patients had a major positive response (such as tumor shrinkage) to the therapy. The largest dose that did not produce many caffeine-related side effects was about 2.5 liters of green tea a day. More clinical trials may be conducted with this dose.
Cancer prevention:
A population survey in China measured the amount of green tea polyphenols in 18,244 men’s urine (an indicator of how much green tea they were consuming) and kept track of which men developed cancers of the stomach or esophagus. After almost 12 years of follow-up, 190 men developed stomach cancer and 42 developed esophageal cancer. Compared to subjects who had not developed cancer, these men had slightly lower levels of ECG, a tea polyphenol, indicating that they probably drank less green tea. However, the researchers in this study only did urine measurements once, at the beginning of the study. Doing multiple measurements at different times would have been a better indicator of average long-term green tea intake.
A population survey in Japan compared green tea intake and other health habits with development of stomach cancer. After surveying 26,311 people, the researchers found no association between green tea and risk of gastric cancer. Although a population study in Japan may not reflect what might happen in other countries, it seems that drinking green tea does not prevent stomach cancer.
The FDA has recently issued a letter according to which there is no credible evidence to support the claims that green tea reduces the risk of certain cancers. The letter also states that it is ‘highly unlikely’ that green tea can reduce the risk of breast and prostate cancers.
Cholesterol-Lowering Effect:
240 adults were given either theaflavin-enriched green tea extract or a placebo in a clinical trial. After 12 weeks, patients in the tea extract group have significantly lower low-density lipoprotein cholesterol (LDL-C) then the placebo group. Theaflavin-enriched green tea extract can be used together other dietary approaches to reduce LDL-C.
Prevention of High Blood Pressure:
In one study, the effect of tea drinking is examined in 1507 subjects. Consumption of around 1 to 3 cup of green tea a day for 1 year can reduce the risk of high blood pressure by 46%. Risk is further reduced if the consumption is increased to more than 3 cups a day.