Green Tea


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The use of dietary supplements by cancer patients has risen significantly over the past 2 decades despite insufficient evidence of safety and effectiveness. Finding reliable sources of information about dietary supplements can be daunting. Patients typically rely on family, friends, and the Internet, often receiving misleading information. 

The ASCO Post’s Integrative Oncology series is intended to facilitate the availability of evidence-based information on alternative and complementary therapies commonly used by patients with cancer. We selected green tea for this issue because of its continued worldwide popularity as an antioxidant powerhouse, sought by many to prevent and treat cardiovascular disease and cancer.

Green Tea

Scientific Name: Camellia sinensis
Common Names: Chinese tea, green tea extract, green tea polyphenols, epigallocatechin gallate (EGCG)

Overview

Green tea, a beverage consumed worldwide for its purported health benefits, is derived from the leaves of the plant Camellia sinensis. Cultivated originally in East Asia, the plant is now grown in the Middle East and in some parts of Africa.

The leaves used to prepare green tea are unfermented. Instead, they are steamed or heated immediately following harvest. This process preserves the integrity of polyphenols, compounds that act as antioxidants and contribute to the beneficial effects of green tea, by minimizing their oxidation.

Green tea has a long history of use in traditional medicine as a stimulant, diuretic, for wound healing, to promote digestion, and to improve heart health. More recently, green tea and its extracts have been utilized to prevent and treat hyperlipidemia, hypertension, atherosclerosis, and cancer. Green tea is available as a dietary supplement in the form of capsules, extracts, and ointments for external application.

However, despite wide consumption of green tea for cancer prevention, current data in support of that use are inconclusive. Green tea products also can interact with several prescription drugs, including anticancer agents. Patients should consult their physicians before taking green tea in any form.

The Science

Green tea has been studied extensively over the past few decades.

Clinical trials indicate that regular consumption of green tea may reduce the risk of hypertension1 and positively affect mood.2 It also enhances glucose tolerance in healthy individuals,3 but does not improve insulin sensitivity or glycemic control in those with type II diabetes.4

Green tea may reduce mortality due to cardiovascular disease in both men and women.5

Topical application of green tea extracts has beneficial effects against external genital and perianal warts.6 Sinecatechin, a green tea extract used to treat genital warts, is an FDA-approved drug.

Many preclinical, case-control, and prospective cohort studies indicate that green tea has chemopreventive properties.7-10 However, a meta analysis of epidemiologic studies failed to find its benefits in preventing stomach cancer.11 Future randomized clinical trials may help resolve the ambiguity surrounding the anticancer potential of green tea.

Adverse Effects

Hepatitis12-14; pruritic swelling and darkening of lower lip15; as well as thrombotic thrombocytopenic purpura have been reported following consumption of green tea.16

Animal studies indicate that when consumed during fasting, green tea extract may increase the risk of toxicity.17

Herb-Drug Interactions

Anticoagulants / antiplatelets: Consumption of large amounts of green tea (0.5–1.0 gallon/d) may provide enough vitamin K to antagonize the effects of anticoagulants and antiplatelet agents. This effect has not yet been reported in humans.18

Bortezomib: EGCG and other polyphenols in green tea can inhibit the therapeutic effects of bortezomib (Velcade) and other boronic acid based proteasome inhibitors.19

Tamoxifen: EGCG was shown to increase the oral bioavailability of tamoxifen.20

Verapamil: The bioavailability of verapamil increased significantly in the presence of EGCG, thought to be due to P-glycoprotein inhibition by EGCG.21

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.22

UGT (uridine 5’-diphospho-glucuronosyltransferase) substrates: Green tea modulates UGT enzymes in vitro and can increase the side effects of drugs metabolized by them.23

Cytochrome P450 3A4 substrates: Green tea extract inhibits CYP3A4 and can affect the intracellular concentration of drugs metabolized by this enzyme.24

Acetaminophen: Green tea increased acetaminophen-induced hepatotoxicity in mice when administered following acetaminophen.25 

Disclosure: Drs. Cassileth and Yeung and Ms. Gubili reported no potential conflicts of interest.

References

1. Yang YC, Lu FH, Wu JS, et al: The protective effect of habitual tea consumption on hypertension. Arch Intern Med 164:1534-1540, 2004.

2. Brown AL, Lane J, Coverly J, et al: Effects of dietary supplementation with the green tea polyphenol epigallocatechin-3-gallate on insulin resistance and associated metabolic risk factors: Randomized controlled trial. Br J Nutr 101:886-894, 2009.

3. Venables MC, Hulston CJ, Cox HR, et al: Green tea extract ingestion, fat oxidation, and glucose tolerance in healthy humans. Am J Clin Nutr 87:778-784, 2008.

4. Mackenzie T, Leary L, Brooks WB: The effect of an extract of green and black tea on glucose control in adults with type 2 diabetes mellitus. Metabolism 56:1340-1344, 2007.

5. 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 296:1255-1265, 2006.

6. Stockfleth E, Beti H, Orasan R, et al: Topical polyphenon E in the treatment of external genital and perianal warts. Br J Dermatol 158:1329-1338, 2008.

7. Pisters KM, Newman RA, Coldman B, et al: Phase I trial of oral green tea extract in adult patients with solid tumors. J Clin Oncol 19:1830-1838, 2001.

8. Sun CL, Yuan JM, Lee MJ, et al: Urinary tea polyphenols in relation to gastric and esophageal cancers. Carcinogenesis 23:1497-1503, 2002.

9. Tsao AS, Liu D, Martin J, et al: Phase II randomized, placebo-controlled trial of green tea extract in patients with high-risk oral premalignant lesions. Cancer Prev Res (Phila) 2:931-941, 2009.

10. Shanafelt TD, Call TG, Zent CS, et al: Phase 2 trial of daily, oral polyphenon E in patients with asymptomatic, Rai stage 0 to II chronic lymphocytic leukemia. Cancer. July 3, 2012 (early release online).

11. Myung SK, Bae WK, Oh SM, et al: Green tea consumption and risk of stomach cancer: A meta-analysis of epidemiologic studies. Int J Cancer 124:670-677, 2009.

12. Mazzanti G, Menniti-Ippolito F, Moro PA, et al: Hepatotoxicity from green tea: A review of the literature and two unpublished cases. Eur J Clin Pharmacol 65:331-341, 2009.

13. Vanstraelen S, Rahier J, Geubel AP: Jaundice as a misadventure of a green tea (Camellia sinensis) lover: A case report. Acta Gastroenterol Belg 71:409-412, 2008.

14. Verhelst X, Burvenich P, Van Sassenbroeck D, et al: Acute hepatitis after treatment for hair loss with oral green tea extracts (Camellia sinensis). Acta Gastroenterol Belg 72:262-264, 2009.

15. Lee JI, Cho BK, Ock SM, et al: Pigmented contact cheilitis: From green tea? Contact Dermatitis 62:60-61, 2010.

16. Liatsos GD, Moulakakis A, Ketikoglou I, et al: Possible green tea-induced thrombotic thrombocytopenic purpura. Am J Health Syst Pharm 67:531-534, 2010.

17. Wu KM: Green tea extract induced lethal toxicity in fasted but not in nonfasted dogs. Int J Toxicol 30:19-20, 2010.

18. Taylor JR, Wilt VM: Probable antagonism of warfarin by green tea. Ann Pharmacother 33:426-428, 1999.

19. Goldin EB, Lam P, Kardosh A, et al: Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid based proteasome inhibitors. Blood 113:5927-5937, 2009.

20. Shin SC, Choi JS: Effects of epigallocatechin gallate on the oral bioavailability and pharmacokinetics of tamoxifen and its main metabolite, 4-hydroxytamoxifen, in rats. Anticancer Drugs 20:584-588, 2009.

21. Chung JH, Choi DH, Choi JS: Effects of oral epigallocatechin gallate on the oral pharmacokinetics of verapamil in rats. Biopharm Drug Dispos 30:90-93, 2009.

22. Lin LC, Wang MN, Tsai TH: Food-drug interaction of (-)-epigallocatechin-3-gallate on the pharmacokinetics of irinotecan and the metabolite SN-38. Chem Biol Interact 174:177-182, 2008.

23. Mohamed ME, Frye RF: Effects of herbal supplements on drug glucuronidation. Review of clinical, animal, and in vitro studies. Planta Med 77:311-321, 2011.

24. Wanwimolruk S, Wong K, Wanwimolruk P: Variable inhibitory effect of different brands of commercial herbal supplements on human cytochrome P-450 CYP3A4. Drug Metabol Drug Interact 24:17-35, 2009.

25. Salminen WF, Yang X, Shi Q, et al: Green tea extract can potentiate acetaminophen-induced hepatotoxicity in mice. Food Chem Toxicol 50:1439-1446, 2012.

Compiled by Barrie R. Cassileth, PhD, and Jyothi Gubili, MS, Memorial Sloan-Kettering Cancer Center. The About Herbs website is managed by K. Simon Yeung, PharmD, MBA, Lac, Memorial Sloan-Kettering Cancer Center.



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