Green Tea

• How It Works

  Green tea may help lower cholesterol. Evidence of its cancer preventive effects in humans is not conclusive.

  Green tea contains substances called polyphenols, which scientists think contribute to its anticancer activity. Laboratory studies of one polyphenol, catechin epigallocatechin-3-gallate (EGCG), show that it may interfere with several processes involved in cell replication, causing tumor cell death. It also might slow the formation of blood vessels around tumors. Epigallocatechin (ECG), another polyphenol, stops leukemic cells from multiplying in laboratory studies. As an antioxidant, green tea may repair cell damage, but whether it can prevent cancer is uncertain. It is also unknown how it might help protect the heart, but it reduces LDL (“bad”) cholesterol and increases HDL (“good”) cholesterol. Tannins present in green tea generally have antibacterial properties.

  Animal studies indicate that oral consumption of green tea extract during fasting can increase the risk of toxicity. It may also interact with various drugs. Human studies are needed.

• Purported Uses
  • As an antioxidant
    There is mixed evidence.
  • To prevent and treat cancer
    Although laboratory studies show an anti-cancer effect, a few clinical trials and population surveys show mixed results. A number of studies in China have suggested that high intake may protect against cancers of the colon and stomach.
  • To lower cholesterol and prevent heart disease
    One clinical trial showed that a theaflavin-enriched green tea extract can be used with other dietary approaches to lower a certain type of cholesterol. A few studies suggest possible benefits with drinking green tea on some risk factors for heart disease, but additional studies are needed.
  • To improve mental functioning; for clear thinking
    Caffeinated forms of green tea may stimulate the nervous system.
  • To lower high blood pressure
    Studies show a reduction in the risk of developing high blood pressure.
  • To prevent tooth decay
    Laboratory studies show that green tea may prevent bacteria from attaching to teeth. This use has not been tested in clinical trials.
  • To lose weight
    One human study shows increased expenditure of energy.
  • To increase water loss (as a diuretic)
    No studies support this use.
• Patient Warnings

  Infants should not be fed green tea, as it may interfere with iron metabolism and cause anemia.

• Do Not Take If
  • You are pregnant or breastfeeding: Caffeine passes into breast milk and may cause insomnia in the infant.
  • You have a peptic ulcer: Green tea stimulates the production of gastric acid.
  • You are taking adenosine: Caffeine may lessen its effects.
  • You are taking atropine: Green tea may reduce its absorption from the gut and therefore lessen its effects.
  • You are taking codeine: Green tea may reduce its absorption from the gut and therefore lessen its effects.
  • You take warfarin or other blood thinners: In theory, very large amounts on the order of one-half to one gallon per day might lessen the effect of these drugs.
  • You are using bortezomib: Polyphenols can inhibit the effects of this drug.
  • You are taking tamoxifen: Green tea may increase risk of adverse effects of Tamoxifen.
  • You are taking verapamil: Green tea may increase risk of adverse effects of Verapamil.
  • You are taking irinotecan: By inhibiting elimination of irinotecan, EGCG may increase its toxicity.
  • You are taking drugs that are substrates of cytochrome P450 3A4: Green tea may increase the risk of side effects of these drugs.
  • You are taking drugs that are substrates of UGT (Uridine 5’-diphospho-glucuronosyltransferase) enzymes: Green tea may increase the risk of side effects of these drugs.
  • You are taking acetaminophen: Green tea increased liver injury caused by acetaminophen in mice when it was given after acetaminophen.
  • You are taking nadolol: Green tea extract may make it less effective.
  • You are taking palbociclib: Green tea extract may decrease availability of palbociclib, thereby reducing its effectiveness.
• Side Effects
  • Nausea, stomach upset
  • Caffeine can cause insomnia, nervousness, or irritability.

  Case Reports

  • Liver toxicity: Several cases have been associated with consumption of green tea.
  • Swelling, itchiness, and darkening of lower lip: In a 40-year-old woman following use of green tea for several years.
  • Blood clots in small blood vessels: In a 38-year-old woman following green tea supplementation for weight loss.
• Special Point
  • Green tea can reduce the absorption of iron from the gut. It should be taken either 2 hours before or 4 hours after taking an iron supplement.
• Scientific Name

  Camellia sinensis

• Clinical Summary

  Green tea is a beverage derived from the unfermented leaves of a plant native to Asia. The extract is marketed as a dietary supplement to regulate blood sugar, cholesterol, blood pressure, and for weight loss and cancer prevention. Active constituents include the polyphenol epigallocatechin-3-gallate (EGCG), caffeine, and theanine. Green tea consumption may reduce the risk of hypertension ⁽⁹⁾ and cardiovascular disease ⁽¹⁴⁾, and a theaflavin-enriched extract lowered low-density lipoprotein cholesterol (LDL-C) levels ⁽⁸⁾. Green tea intake has also been associated with a reduction in self-reported depression ⁽⁷⁷⁾. Some findings suggest that green tea can enhance glucose tolerance in healthy individuals ^(11) (12), and reduce fasting blood glucose levels ⁽⁷⁸⁾. However, data from studies on obese ^(10) (60) and diabetic patients ⁽¹³⁾ are mixed.

  Topical application of green tea extracts was found effective against external genital and perianal warts ^{(15) (16) (17)}. One such extract, sinecatechin, is an FDA-approved drug indicated for this use.

  Green tea and its active compounds have been studied for their cancer preventive potential. In vitro studies suggest chemopreventive ⁽¹⁾ and antiangiogenic ⁽⁴⁾ effects.

  Preliminary human studies suggest preventive benefits with green tea extracts among patients with oral premalignant lesions ⁽⁴¹⁾, or at high-risk of developing liver ⁽⁶¹⁾ or colorectal cancers ⁽⁶⁴⁾. Another extract produced beneficial biologic responses in patients with chronic lymphocytic leukemia ⁽⁵²⁾.

  EGCG, applied topically, can help relieve radiation-induced dermatitis in breast cancer patients ^(74) (75). In addition, oral EGCG consumption was found to be effective against acute radiation-induced esophagitis in lung cancer patients ⁽⁷⁶⁾. However, an EGCG-enriched green tea was not useful as maintenance intervention in women with advanced stage ovarian cancer after standard treatment ⁽⁷¹⁾, and EGCG supplementation did not reduce likelihood of prostate cancer ⁽⁶³⁾.

  In other prostate cancer studies, supplementation with a blend of green tea, pomegranate, broccoli, and curcumin had a protective effect in prostate cancer patients following post-radical treatment ⁽⁵⁹⁾. Green tea consumption decreased PSA levels in prostate cancer patients prior to prostatectomy ⁽⁷²⁾. However, higher doses of green tea catechins were associated with elevated incidence of prostate cancer in men with high grade prostatic intraepithelial neoplasia and/or atypical small acinar proliferation ⁽⁷³⁾.

  Data on whether green tea can reduce gastric and esophageal cancer risk are mixed ^{(5) (6) (42)}. It was also not associated with risk of developing malignant lymphoma or multiple myeloma ⁽⁶⁵⁾, although data suggest tea intake reduced risk of myelodysplastic syndrome ⁽⁵⁶⁾. Other data suggest that consumption may actually increase breast cancer risk in postmenopausal women ⁽⁶²⁾. Future studies are needed to resolve this ambiguity.

  The caffeinated form 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. Animal studies indicate that oral consumption of green tea extract during fasting can increase the risk of toxicity ⁽⁴⁹⁾. In humans, EGCG intake (200 mg, twice daily for one year) was shown to be safe ⁽⁷⁰⁾ based on clinical data, whereas a daily dose amounting to 800 mg EGCG was associated with elevated liver enzymes, which was reversible with consumption cessation ⁽⁶⁷⁾. It is important to distinguish food from concentrated supplements because the dosage varies considerably, and that in turn can either confer benefit or cause harmful effects.

• Purported Uses
  • Cancer prevention
  • Cancer treatment
  • Cardiovascular disease
  • Cognitive improvement
  • GI disorders
  • Hypertension
  • Weight loss
• Mechanism of Action

  Green tea is thought to confer cardiovascular protection by increasing HDL cholesterol and lowering LDL cholesterol and triglycerides ^(8) (29), as well as by blocking platelet aggregation. The tannins may have antibacterial properties ⁽²⁸⁾ and can produce antidiarrheal effects. The flavonoid constituents may reduce lipoprotein oxidation ⁽³⁰⁾.

  Modulation of blood pressure by green tea is thought to be mediated through EGCG. It induces nitric oxide (NO) production via activation of endothelial NO synthase, resulting in vasodilation ⁽²⁷⁾. In healthy subjects, a green tea extract modulated effective brain connectivity during working memory processing ⁽⁵⁵⁾. EGCG inhibited aggregation of tau protein, thereby reducing toxicity in neuronal model cells ⁽⁵⁷⁾.

  Anticancer activities have been related to polyphenol content, with chemopreventive properties attributed to EGCG via apoptotic induction and tumor antiangiogenesis ⁽²⁰⁾. EGCG may inhibit enzymes involved in cell replication and DNA synthesis by interfering with cell-to-cell adhesion or 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⁾. It also inhibited DNA replication in leukemia cancer cell lines ⁽²⁴⁾, and modulated vascular endothelial growth factor (VEGF) leading to apoptosis in leukemic cells ⁽⁷⁾.

  Administration of green tea inhibits UVB light-induced carcinogenesis; when given before and during carcinogen treatment, it reduced incidence and number of stomach and esophageal tumors in mice ⁽²⁵⁾.

• Warnings
  • 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 breastfeed should limit their intake because of caffeine content.
  • Because tea can pass into breast milk, it may cause sleep disorders in nursing infants. Ingestion by infants has been linked to impaired iron metabolism and microcystic anemia.
  • Individuals with peptic ulcers should avoid drinking because it can stimulate the production of gastric acid ⁽²⁹⁾.
• Adverse Reactions
  • Green tea is generally considered safe, but because of the caffeine content, excessive consumption can disrupt sleep and cause headaches. A few cases of hepatotoxicity have also been associated with green tea extracts containing high EGCG levels ^{(44) (46) (47) (58)}.
  • Adverse reactions appear to be dose dependent. Clinical trials reported the following effects:
    — Nausea, abdominal pain, and transaminitis after intake of high dose EGCG (2000 mg orally twice per day) in patients with early stage chronic lymphocytic leukemia ⁽⁵²⁾
    — Elevation in alanine aminotransferase (ALT) levels, also after consumption of high amounts of EGCG (843 mg daily for one year) by postmenopausal women at risk for breast cancer ⁽⁶⁸⁾
    — In another study of EGCG in breast cancer patients, rectal bleeding (with 800mg daily), weight gain, indigestion and insomnia (daily dose of 1200 mg), and liver function abnormality (at 1,600 mg daily) were reported ⁽⁶⁹⁾.
    However, in a study of men with high-grade prostatic intraepithelial neoplasia (HGPIN) and/or atypical small acinar proliferation (ASAP), EGCG (200 mg, twice daily for one year) was shown to be safe ⁽⁷⁰⁾.
  • Pruritic swelling and darkening of lower lip following green tea consumption for several years ⁽⁴⁵⁾ and thrombotic thrombocytopenic purpura after taking a green tea supplement for weight loss ⁽⁴⁸⁾ have also been reported.
  • When consumed during fasting, green tea extract increased the risk of toxicity in animal studies. Whether it has the same effect in humans is not known ⁽⁴⁹⁾.
• Herb-Drug Interactions
  • Adenosine: The caffeine content may inhibit the hemodynamic effects of adenosine ⁽¹⁸⁾.
  • Anticoagulants / Antiplatelets: Theoretically, consumption of large amounts (.5-1 gallon/day) may provide enough vitamin K to antagonize the effects of anticoagulants and antiplatelet agents, though this effect has not been reported in humans ^(29) (34).
  • Atropine: The tannin content may reduce the absorption of atropine.
  • Iron supplements: The tannin content in may reduce the bioavailability of iron. Green tea should be taken either 2 hours before or 4 hours following iron administration.
  • Codeine: The tannin content may reduce the absorption of codeine ⁽¹⁸⁾.
  • Bortezomib: EGCG and other polyphenols can inhibit the therapeutic effect of bortezomib and other boronic acid based proteasome inhibitors ⁽³⁷⁾.
  • Tamoxifen: EGCG was shown to increase the oral bioavailability of tamoxifen, increasing the potential for their interactions ⁽³⁸⁾.
  • Verapamil: The bioavailability of verapamil increased significantly in the presence of EGCG, thought to be due to P-glycoprotein inhibition by EGCG ⁽³⁹⁾.
  • Irinotecan: A study found EGCG to inhibit transport of irinotecan and its metabolite SN-38 into biliary elimination, resulting in their prolonged half-life which can increase toxicity ⁽⁴⁰⁾.
  • Cytochrome P450 3A4 substrates: Green tea extract inhibits CYP 3A4 enzyme and can affect the intracellular concentration of drugs metabolized by this enzyme ^(43) (44).
  • UGT (Uridine 5’-diphospho-glucuronosyltransferase) substrates: Green tea modulates UGT enzymes in vitro and can increase the side effects of drugs metabolized by them ⁽⁵¹⁾.
  • Acetaminophen: Green tea was shown to increase acetaminophen-induced hepatotoxicity in mice when administered following acetaminophen  ⁽⁵³⁾.
  • Nadolol: Green tea extract inhibits OATP1A2 transporter and can reduce the absorption and plasma concentration of substrate drugs, like nadolol ⁽⁵⁴⁾.
  • Palbociclib: The bioavailability of Palbociclib decreased following administration of green tea extract in a murine model ⁽⁷⁹⁾. Clinical relevance has yet to be determined.
• Herb Lab Interactions
  • Caffeine in green tea may increase PT / PTT
• References

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  4. Sartippour MR, et al. Green tea inhibits vascular endothelial growth factor (VEGF) induction in human breast cancer cells. J Nutr 2002;132:2307-11.

  5. Sun CL, et al. Urinary tea polyphenols in relation to gastric and esophageal cancers: a prospective study of men in Shanghai, China. Carcinogenesis 2002;23:1497-503.

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  7. Lee YK, 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 2004;104(3):788-94.

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