Green Tea (Camellia sinensis)

ALSO KNOWN AS: Chinese tea, green tea extract, green tea polyphenols, epigallocatechin gallate (EGCG).

BACKGROUND: Green tea, derived from the leaves of Camellia sinensis, is consumed widely in Asia. Originally cultivated in East Asia, the plant is now grown in the Middle East and in some parts of Africa. Green tea has gained global popularity over the last few decades.

The leaves used to produce green tea are unfermented. They are steamed or heated immediately following harvest. This minimizes oxidation of the polyphenols, which are compounds that act as antioxidants and are thought to confer the health benefits attributed to green tea.

Green tea has been used in traditional medicine as a stimulant, as a diuretic, for wound healing, to promote digestion, and to improve heart health. More recently, green tea and its extracts have been used to prevent and treat hyperlipidemia, hypertension, atherosclerosis, and cancer.

Green tea is available as a dietary supplement in capsule form, as an extract, and in ointments for external application.

TAKE HOME POINTS

For additional information, visit the Memorial Sloan-Kettering Cancer Center Integrative Medicine Service website, “About Herbs,” at

http://www.mskcc.org/AboutHerbs

.

RESEARCH: The active constituent of green tea extract is EGCG, which accounts for 40% of its total polyphenol content. Regular consumption of green tea may reduce the risk of hypertension[1] and positively affect mood.[2] It also enhances glucose tolerance in healthy individuals[3] but did not improve insulin sensitivity or glycemic control in those with type 2 diabetes.[4] Green tea also may reduce mortality due to cardiovascular disease in both men and women.[5] Topical application of green tea extracts was shown to be effective against external genital and perianal warts.[6] A green tea extract, sinecatechin, used for genital warts, is an FDAapproved drug.

Several pre-clinical, case-control and prospective cohort studies show that green tea has chemopreventive properties.[7-9] However, a metaanalysis of epidemiologic studies failed to find that green tea prevents stomach cancer.[10] The FDA recently concluded that green tea is unlikely to reduce the risk of breast or prostate cancer.[11] Randomized clinical trials, currently underway, may help resolve the uncertainty surrounding the anticancer potential of green tea.

ADVERSE REACTIONS: Several cases of hepatitis have been associated with consumption of green tea.[12-14] A 40-year-old woman developed pruritic swelling and darkening of the lower lip following use of green tea for several years. Symptoms resolved after she discontinued consumption of green tea. [15] A 38-year-old woman developed thrombotic thrombocytopenic purpura following green tea supplementation for weight loss.[16]

Animal studies indicate that oral consumption of green tea extract while fasting can increase the risk of toxicity.[17]

HERB-DRUG INTERACTIONS:Anticoagulants/ antiplatelets: Theoretically, consumption of large amounts of green tea (0.5–1.0 gallon/day) may provide enough vitamin K to antagonize the effects of anticoagulants and antiplatelet agents, although this effect has not been reported in humans.[18]

Bortezomib (Velcade): EGCG and other polyphenols in green tea can inhibit the therapeutic effect of bortezomib 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, an effect thought to be due to P-glycoprotein inhibition by EGCG.[21]

Irinotecan: A study found EGCG to inhibit the transport of irinotecan and its metabolite SN-38 into biliary elimination, resulting in prolongation of their half-life, which can increase toxicity.[22]

Cytochrome P450 3A4 substrates: Green tea extract inhibits CYP3A4 and can affect the intracellular concentration of drugs metabolized by this enzyme.[12]

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

References:

REFERENCES

1.Yang YC, et al. The protective effect of habitual tea consumption on hypertension. Arch Intern Med. 2004;164:1534-40.

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. 101:886-94.

3. Venables MC, Hulston CJ, Cox HR, Jeukendrup AE. Green tea extract ingestion, fat oxidation, and glucose tolerance in healthy humans. Am J Clin Nutr. 2008;87:778-84.

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: double-blind randomized study. Metabolism. 2007;56:1340-4.

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. 2006;296:1255-65.

6. Stockfleth E, Beti H, Orasan R, et al. Topical polyphenon E in the treatment of external genital and perianal warts: a randomized controlled trial.Br J Dermatol. 2008;158:1329-38.

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. 2001;19:1830-8.

8. Sun CL, Yuan JM, Lee MJ, 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.

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 Pa). 2009;2:931-41.

10. 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. 2009;124:670-7.

11. Letter from FDA. Green tea and cancer. Available from: http://www.fda.gov/Food/LabelingNutrition/LabelClaims/QualifiedHealthClaims/ucm073992.htm#gtea. Issued February 24, 2011. Accessed October 18, 2011.

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. 2009;65:331-41.

13. Vanstraelen S, Rahier J, Geubel AP. Jaundice as a misadventure of a green tea (Camellia sinensis) lover : a case report. Acta Gastroenterol Belg. 2008;71:409-12.

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. 2009;72:262-4.

15. Lee JI, Cho BK, Ock SM, Park HJ. Pigmented contact cheilitis: from green tea? Contact Dermatitis. 2010;62:60-1.

16. Liatsos GD, Moulakakis A, Ketikoglou I, Klonari S. Possible green tea-induced thrombotic thrombocytopenic purpura. Am J Health Syst Pharm. 2010;67:531-4.

17. Wu KM. Green tea extract induced lethal toxicity in fasted but not in nonfasted dogs. Int J Toxicol. 2010;(1):19-20

18. Taylor JR, Wilt VM. Probable antagonism of warfarin by green tea. Ann Pharmacother 1999;33:426-8.

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. 2009;113:5927-37.

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. 2009;20:584-8.

21. Chung JH, Choi DH, Choi JS. Effects of oral epigallocatechin gallate on the oral pharmacokinetics of verapamil in rats. Biopharm Drug Dispos. 2009;30:90-3.

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. 2008;174:177-82.

23. Mohamed ME, Frye RF. Effects of herbal supplements on drug glucuronidation. Review of clinical, animal, and in vitro studies. Planta Med. 2011;77:311-21.