Natural Products (Professional)

Green Tea

Scientific Name(s): Camellia sinensis (L.) Kuntze. Family: Theaceae

Common Name(s): Tea , green tea , black tea , oolong tea

Clinical Overview

Uses of Green Tea

Green tea is traditionally consumed as a beverage. It exhibits strong antioxidant activity and is used primarily for its perceived anticancer, cardioprotective, and calming effects, although clinical studies are lacking.

Green Tea Dosing

Multidose pharmacokinetic studies suggest a daily dose of epigallocatechin gallate 800 mg (approximately equivalent to 16 Japanese-style cups of green tea) for 4 weeks to be safe and well tolerated. Bioavailability of active compounds appears unaffected by the addition of milk to tea, but can be enhanced by the fasting state.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

The Food and Drug Administration advises those who are or may become pregnant to limit caffeine intake.

Green Tea Interactions

Vitamin K present in green tea may antagonize the anticoagulant effect of warfarin.

Green Tea Adverse Reactions

Toxicology

Research reveals little information regarding toxicity with the use of green tea.

Botany

C. sinensis is a large shrub with evergreen leaves native to eastern Asia, where it is cultivated extensively. The plant has leathery, dark green leaves, and fragrant, white flowers with 6 to 9 petals. Cultivated tea plants are trimmed to about 1.5 m to facilitate the harvest. 1

History

The dried, cured leaves of C. sinensis have been used medicinally for more than 5,000 years. Traditional Chinese medicine has recommended drinking green tea for prevention of ill health, which this is still regarded as a healthy practice in Asia. Green tea is less popular in the United States than black tea. 2 , 3 , 4 , 5

Chemistry

The chemistry of tea is complex due to the numerous components formed during the curing and drying process, as well as variations in the harvest season, climate, and horticultural and processing practices. 2 , 5 However, quality control and analytical methods are improving, allowing greater precision in recent clinical studies. 2 , 3 , 6 , 7 , 8 , 9

Tea leaves contain varying amounts of polyphenols, the majority of which are catechins. The leaves also possess smaller quantities of caffeine, theobromine, theophylline, theanine, and phenolic acids. 2 , 4

Other tea constituents include tannins, essential and other volatile oils, B-vitamins, ascorbic acid (present in fresh leaf but destroyed in the making of black tea), folacin, malic, and oxalic acids. 10 , 11 , 12 , 13 , 14 , 15 , 16

The major polyphenol in green tea is (-)-epigallocatechin gallate, with lesser amounts of catechin, epicatechin, gallocatechin, gallocatechin gallate, and epicatechin gallate.

The composition of green tea, prepared by drying and steaming (which inactivates the oxidase enzymatic activity), is similar to that of the fresh leaf except for a few changes that occur rapidly following plucking. 17 The primary difference between green and black tea is in the fermentation process required to produce black tea. Catechins are converted to higher molecular weight theaflavins, which are absent in green tea. Less fermentation results in an intermediary, lighter product known as oolong tea. 2

Decaffeination slightly reduces the catechin content of black tea. 3 , 5 , 18 The addition of milk to tea is not considered to affect the bioavailability of catechins, but may affect the antioxidant potential depending on the fat content of the milk. 3 , 5

Green Tea Uses and Pharmacology

Current research on green tea includes pharmacokinetic and epidemiological studies, cardiovascular and lipid effects, and a wide variety of anticancer studies.

Antioxidant activity

The primary hypothesis for many of tea's health benefits involves the antioxidant capacity of the chemical constituents and has been supported by in vitro experiments and epidemiological studies. 3 , 4 In vitro experiments show a direct effect of tea on reactive oxygen species and the chelation of metal ions, such as iron and copper. 3 , 4 Green tea is considered more active than black tea. 3 , 19 Epicatechin and catechins were ranked most potent of 24 tested plant polyphenolic flavonoids. 3 , 19 The methodology of such experiments is important 20 , 21 , 22 , 23 , 24 , 25 ; most clinical trials have demonstrated that tea consumption improves plasma antioxidant capacity and biomarkers of oxidative stress. 3 , 4 , 19 , 25

Cancer

Epidemiological studies and animal experiments provide evidence of green tea's potential as an anticancer agent. Comprehensive reviews are available but limited in their findings. Nonetheless, a protocol for the meta-analysis of green tea's role in cancer prevention has been published. 26

Mechanisms for the anticancer activity of green tea have been studied in animals and laboratory experiments but have not been demonstrated in humans. Doses used experimentally may not reflect usual tea consumption, and a number of factors may act to produce the relationships reported in epidemiological studies. 3 , 27 , 28 The polyphenols in green tea inhibit cell proliferation. 26 The polyphenol epigallocatechin gallate increases the activity of antioxidants in specific organs in mice, as well as their overall chemoprotective effect in those organs. 3 , 26 , 27 , 28 Epigallocatechin gallate may facilitate direct binding to certain carcinogens. 3 , 26 Polyphenols, especially catechins, may protect cells from tumor development by enhanced gap junction communication between cells. 26 , 28 Tea blocks tumor growth by sealing the receptors of affected cells. Polyphenols may assist inhibition of tumor genesis in the skin, lungs, oral cavity, esophagus, stomach, small intestine, colon, liver, pancreas, ovary, and mammary glands. 26 , 27 , 28 , 29 Green tea polyphenols induce apoptosis in a variety of cells, including human lymphoid leukemia and human prostate cells, 27 , 28 , 29 , 30 , 31 and alter estradiol and sex-hormone binding globulin levels associated with breast cancer risk. 3 , 32

A Cochrane review found no evidence of green tea efficacy in preventing progression to malignancy in leukoplakia. 33

Long-term prospective and case-control studies show an inverse association between tea consumption and risk of cancer of the colon, urinary bladder, stomach, esophagus, lung, pancreas, prostate, and squamous cell. 3 , 28 Increased risk of breast cancer recurrence 28 and delayed onset of cancers in general have been described. 28 , 29 Not all epidemiological studies provide the same results, and confounding variables include social class and lifestyle. A risk of esophageal cancer from tea drinking has been suggested in epidemiological studies, but this also may be attributed to the scalding temperatures at which the beverage is consumed. 3

Cardiovascular

Epidemiological studies and in vitro experiments demonstrate that tea consumption is inversely associated with cardiovascular disease, although a direct cause-effect relationship has not been conclusively demonstrated. 2 , 3 , 34 One meta-analysis suggests that regular intake of tea might reduce the incidence of myocardial infarction and have other cardioprotective effects. However, the studies included in the analysis were too heterogeneous to allow for meaningful interpretation. 2 Mechanisms of action under investigation include reduced low density lipoprotein oxidation, 20 , 21 , 35 , 36 , 37 , 38 enhanced endothelial cell functioning, 34 , 39 effects on atherosclerosis, 3 hypotensive effects, platelet aggregation, and improved cholesterol profiles. 40 , 41

Other uses
Orodental

Evidence for protection against dental caries comes from kinetic and animal models. There are few human trials. Green tea exhibits antimicrobial actions against oral bacteria 2 , 3 , 42 , 43 and provides a natural source of fluoride. 3 Oolong and green tea inhibit bacterial adherence to tooth surfaces and the rate of acid production in animal studies, 3 , 41 while black and green tea inhibit amylase activity. 42

Bone density

Epidemiological studies suggest tea consumption helps protect against osteoporosis in older women, 2 , 3 but animal studies suggest tannins may decrease the absorption of calcium to some extent. 2

Arthritis

Animal studies suggest the antioxidant fractions of tea possess anti-inflammatory properties. 2 , 4

Thermogenesis/Weight control

Placebo-controlled clinical trials suggest thermogenic properties of green tea might contribute to weight control, 2 , 3 , 44 but this has been debated. 44 , 45

Diabetes

A trial of oolong tea in type 2 diabetes revealed that tea reduces plasma glucose levels. 4 , 46

Anxiolytic

Tea is historically known for its calming effects, probably because of L-theanine, an amino acid that produces tranquilizing effects. Theanine is converted to catechins by the tea plant; therefore, the time of harvesting will influence the amount of theanine in the tea. Theanine also is considered to counteract some of the effects of caffeine and to lower cortisol levels during stress periods. 2 , 47

Antimicrobial

Tea has been demonstrated to have in vitro activity against a number of pathogenic bacteria 48 , 49 , 50 and fungi. 51 Activity by epigallocatechin gallate against the HIV virus has been demonstrated in vitro, with direct binding to certain CD4 molecules. 2

Cognitive function

Experiments have suggested that the polyphenols in green tea may help in degenerative disorders, such as Parkinson and Alzheimer diseases. 3 , 52 , 53

Dosage

Pharmacokinetic studies of tea have been conducted in humans, with measurable levels of various chemical compounds found in plasma, feces, and urine. 18 , 54 , 55 , 56 , 57 , 58 , 59 Multidose pharmacokinetic studies suggest a daily dose of epigallocatechin gallate 800 mg capsules (approximately equivalent to 16 Japanese-style cups of green tea) for 4 weeks to be safe and well tolerated. 58 Dosing using tea extract capsules eliminates the unwanted effect of high caffeine and liquid volume intake as a consequence of drinking large quantities of brewed tea and could be used to standardize clinical trials. 3 Bioavailability of active compounds appears unaffected by the addition of milk to tea, but can be enhanced by the fasting state. 3 , 5 , 24 , 59 , 60

Pregnancy/Lactation

Category C . Safety for use in pregnancy has not been established. Caffeine crosses the placenta and produces fetal blood and tissue levels similar to maternal concentrations. Excessive caffeine intake (greater than 600 mg/day) has been weakly associated with increased fetal loss, low birth weight, premature delivery, an increase in fetal breathing activity, and a fall in baseline fetal heart rate. 61 Caffeine appears in the breast milk of breast-feeding mothers.

Interactions

Case reports suggest probable antagonism of warfarin by the vitamin K content in green tea when more than 4 cups per day are ingested. 62

Adverse Reactions

There are no reports of clinical toxicity from daily tea consumption. Adverse reactions recorded in pharmacokinetic studies in humans using tea extracts include headache, dizziness, and GI symptoms. 56 Epidemiological studies suggest a detrimental effect of tea drinking on iron status, but data inconsistently cite multiple confounding influences. 63 Dose-dependent inhibition of intestinal non-heme iron absorption was demonstrated in a controlled clinical trial using epigallocatechin gallate. 64 Other published studies report that black tea reduces iron absorption more than green tea, suggesting the type of polyphenol in tea to be an important factor. 64

Coadministration of tea extracts and iron products is not advised. Patients with poor iron status should avoid drinking tea with meals because iron absorption may be impaired. 3 , 63 A beneficial effect of tea drinking with meals was suggested in a trial of patients with genetic hemochromatosis. 3

Some studies suggest that tea consumption may affect oxalate absorption and contribute to the formation of kidney stones; however, epidemiological studies have shown an inverse relationship. 3

Toxicology

Research reveals little or no information regarding toxicity with the use of green tea.

Bibliography

1. USDA, NRCS. 2004. The PLANTS Database, Version 3.5 ( http://plants.usda.gov ). National Plant Data Center, Baton Rouge, LA 70874-4490 USA.
2. Cooper R , Morré DJ , Morré DM . Medicinal benefits of green tea: Part I. Review of noncancer health benefits . J Altern Complement Med . 2005;3:521-528.
3. McKay DL , Blumberg JB . The role of tea in human health: an update . J Am Coll Nutr . 2002;21:1-13.
4. Siddiqui IA , Afaq F , Adhami VM , Ahmad N , Mukhtar H . Antioxidants of the beverage tea in promotion of human health . Antioxid Redox Signal . 2004;6:571-582.
5. Blumberg J . Introduction to the proceedings of the Third International Scientific Symposium on Tea and Human Health: Role of Flavonoids in the Diet . J Nutr . 2003;133:3244S-3246S.
6. Nakagawa K , Okuda S , Miyazawa T . Dose-dependent incorporation of tea catechins, (-)-epigallocatechin-3-gallate and (-)-epigallocatechin, into human plasma . Biosci Biotechnol Biochem . 1997;61:1981-1985.
7. Unno T , Kondo K , Itakura H , Takeo T . Analysis of (-)-epigallocatechin gallate in human serum obtained after ingesting green tea . Biosci Biotechnol Biochem . 1996;60:2066-2068.
8. Dalluge JJ , Nelson BC , Thomas JB , Welch MJ , Sander LC . Capillary liquid chromatography/electrospray mass spectrometry for the separation and detection of catechins in green tea and human plasma . Rapid Commun Mass Spectrom . 1997;11:1753-1756.
9. Maiani G , Serafini M , Salucci M , Azzini E , Ferro-Luzzi A . Application of a new high-performance liquid chromatographic method for measuring selected polyphenols in human plasma . J Chromatogr B Biomed Sci Appl . 1997;692:311-317.
10. Dalluge JJ , Nelson BC , Thomas JB , Sander LC . Selection of column and gradient elution system for the separation of catechins in green tea using high-performance liquid chromatography . J Chromatogr A . 1998;793:265-274.
11. Miketova P , Schram KH , Whitney JL , et al. Mass spectrometry of selected components of biological interest in green tea extracts . J Nat Prod . 1998;61:461-467.
12. Watanabe J , Kawabata J , Niki R . Isolation and identification of acetyl-CoA carboxylase inhibitors from green tea ( Camellia sinensis ) . Biosci Biotechnol Biochem . 1998;62:532-534.
13. Savolainen H . Tannin content of tea and coffee . J Appl Toxicol . 1992;12:191-192.
14. Mazur WM , Wahala K , Rasku S , Salakka A , Hase T , Adlercreutz H . Lignan and isoflavonoid concentrations in tea and coffee . Br J Nutr . 1998;79:37-45.
15. Fukushima S , Akahori Y , Tsuneya T . Studies on the essential oil of green tea [in Janpanese]. Yakugaku Zasshi . 1969;89:1729-1731.
16. Chen TS , Lui CK , Smith CH . Folacin content of tea . J Am Diet Assoc . 1983;82:627-632.
17. Graham HN . Green tea composition, consumption, and polyphenol chemistry . Prev Med . 1992;21:334-350.
18. Chow HH , Cai Y , Hakim IA , et al. Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals . Clin Cancer Res . 2003;9:3312-3339.
19. Luczaj W , Skrzydlewska E . Antioxidative properties of black tea . Prev Med . 2005;40:910-918.
20. Hodgson JM , Puddey IB , Croft KD , et al. Acute effects of ingestion of black and green tea on lipoprotein oxidation . Am J Clin Nutr . 2000;71:1103-1107.
21. Erba D , Riso P , Bordoni A , Foti P , Biagi PL , Testolin G . Effectiveness of moderate green tea consumption on antioxidative status and plasma lipid profile in humans . J Nutr Biochem . 2005;16:144-149.
22. Hakim IA , Harris RB , Brown S , et al. Effect of increased tea consumption on oxidative DNA damage among smokers: a randomized controlled study . J Nutr . 2003;133:3303S-3309S.
23. Young JF , Dragstedt LO , Haraldsdottir J , et al. Green tea extract only affects markers of oxidative status postprandially: lasting antioxidant effect of flavonoid-free diet . Br J Nutr . 2002;87:343-355.
24. Leenean R , Roodenburg AJ , Tijburg LB , Wiseman SA . A single dose of tea with or without milk increases plasma antioxidant activity in humans . Eur J Clin Nutr . 2000;54:87-92.
25. Rietveld A , Wiseman S . Antioxidant effects of tea: evidence from human clinical trials . J Nutr . 2003;133:3285S-3292S.
26. Schmidt K , Horneber M , Borrelli F , Ernst E . Green tea ( Camellia sinensis ) for the prevention of cancer (Protocol) . Cochrane Database Syst Rev . 2004;(4).
27. Lambert JD , Yang CS . Cancer chemopreventive activity and bioavailability of tea and tea polyphenols . Mutat Res . 2003;523-524:201-208.
28. Cooper R , Morré DJ , Morré DM . Medicinal benefits of green tea: Part ΙΙ. review of anticancer properties . J Altern Complement Med . 2005;11:639-652.
29. Fujiki H , Suganuma M , Okabe S , et al. Cancer prevention with green tea and monitoring by a new biomarker, hnRNP B1 . Mutat Res . 2001;480-481:299-304.
30. Chung FL , Schwartz J , Herzog CR , Yang YM . Tea and cancer prevention: studies in animals and humans . J Nutr . 2003;133:3268S-3274S.
31. Hou Z , Lambert JD , Chin KV , Yang CS . Effects of tea polyphenols on signal transduction pathways related to cancer chemoprevention . Mutat Res . 2004;555:3-19.
32. Nagata C , Kabuto M , Shimizu H . Association of coffee, green tea, and caffeine intakes with serum concentrations of estradiol and sex hormone-binding globulin in premenopausal Japanese women . Nutr Cancer . 1998;30:21-24.
33. Lodi G , Sardella A , Bez C , Demarosi F , Carrassi A . Interventions for treating oral leukoplakia . Cochrane Database Syst Rev . 2004;(3):CD001829.
34. Vita JA . Tea consumption and cardiovascular disease: effects on endothelial function . J Nutr . 2003;133:3293S-3297S.
35. McAnlis GT , McEneny J , Pearce J , Young IS . Black tea consumption does not protect low density lipoprotein from oxidative modification . Eur J Clin Nutr . 1998;52:202-206.
36. Hodgson JM , Croft KD , Mori TA , Burke V , Beilin LJ , Puddey IB . Regular ingestion of tea does not inhibit in vivo lipid peroxidation in humans . J Nutr . 2002;132:55-58.
37. Princen HM , van Duyvenvoorde W , Buytenhek R , et al. No effect of consumption of green and black tea on plasma lipid and antioxidant levels and on LDL oxidation in smokers . Arterioscler Thromb Vasc Biol . 1998;18:833-841.
38. de Maat MP , Pijl H , Kluft C , Princen HM . Consumption of black and green tea had no effect on inflammation, haemostasis and endothelial markers in smoking healthy individuals . Eur J Clin Nutr . 2000;54:757-763.
39. Nagaya N , Yamamoto H , Uematsu M , et al. Green tea reverses endothelial dysfunction in healthy smokers . Heart . 2004;90:1485-1486.
40. Hodgson JM , Puddey IB , Burke V , Beilin LJ , Jordan N . Effects on blood pressure of drinking green and black tea . J Hypertens . 1999;17:457-463.
41. Riemersma RA , Rice-Evans CA , Tyrrell RM , Clifford MN , Lean ME . Tea flavonoids and cardiovascular health . QJM . 2001;94:277-282.
42. Hamilton-Miller JM . Anti-cariogenic properties of tea ( Camellia sinensis ) . J Med Microbiol . 2001;50:299-302.
43. Koo MW , Cho CH . Pharmacological effects of green tea on the gastrointestinal system . Eur J Pharmacol . 2004;500:177-185.
44. Dulloo AG , Duret C , Rohrer D , et al. Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans . Am J Clin Nutr . 1999;70:1040-1045.
45. Kovacs EM , Lejeune MP , Nijs I , Westerterp-Plantenga MS . Effects of green tea on weight maintenance after body-weight loss . Br J Nutr . 2004;91:431-437.
46. Hosoda K , Wang MF , Liao ML , et al. Antihyperglycemic effect of oolong tea in type 2 diabetes . Diabetes Care . 2003;26:1714-1718.
47. Lu K , Gray MA , Oliver C , et al. The acute effects of L-theanine in comparison with alprazolam on anticipatory anxiety in humans . Hum Psychopharmacol . 2004;19:457-465.
48. Toda M , Okubo S , Ohnishi R , Shimamura T . Antibacterial and bactericidal activities of Japanese green tea [in Japanese]. Nippon Saikingaku Zasshi . 1989;44:669-672.
49. Yam TS , Shah S , Hamilton-Miller JM . Microbiological activity of whole and fractionated crude extracts of tea and of tea components . FEMS Microbiol Lett . 1997;152:169-174.
50. Isogai E , Isogai H , Takeshi K , Nishikawa T . Protective effect of Japanese green tea extract on gnotobiotic mice infected with an Escherichia coli O157:H7 strain . Microbiol Immunol . 1998;42:125-128.
51. Bezbaruah B , Kumar BS , Barthakur M . Fungicidal and insect controlling properties of Proteus strain RRLJ 16, isolated from tea, Camellia sinensis (L) O Kuntze, plantations . Indian J Exp Biol . 1996;34:706-709.
52. Mandel S , Weinreb O , Amit T , Youdim MB . Cell signaling pathways in the neuroprotective actions of the green tea polyphenol (-)-epigallocatechin-3-gallate: implications for neurodegenerative diseases . J Neurochem . 2004;88:1555-1569.
53. Weinreb O , Mandel S , Amit T , Youdim MB . Neurological mechanisms of green tea polyphenols in Alzheimer's and Parkinson's diseases . J Nutr Biochem . 2004;15:506-516.
54. Chow HH , Cai Y , Alberts DS , et al. Phase I pharmacokinetic study of tea polyphenols following single-dose administration of epigallocatechin gallate and polyphenon E . Cancer Epidemiol Biomarkers Prev . 2001;10:53-58.
55. Spencer JP . Metabolism of tea flavonoids in the gastrointestinal tract . J Nutr . 2003;133:3255S-3261S.
56. Henning SM , Niu Y , Lee NH , et al. Bioavailability and antioxidant activity of tea flavanols after consumption of green tea, black tea, or a green tea extract supplement . Am J Clin Nutr . 2004;80:1558-1564.
57. He YH , Kies C . Green and black tea consumption by humans: impact on polyphenol concentrations in feces, blood and urine . Plant Foods Hum Nutr . 1994;46:221-229.
58. Mulder TP , Rietveld AG , von Amelsvoort JM . Consumption of both black tea and green tea results in an increase in the excretion of hippuric acid into urine . Am J Clin Nutr . 2005;81(1 suppl):256S-260S.
59. Chow HH , Hakim IA , Vining DR , et al. Effects of dosing condition on the oral bioavailability of green tea catechins after single-dose administration of Polyphenon E in healthy individuals . Clin Cancer Res . 2005;11:4627-4633.
60. van het Hof KH , Kivits GA , Weststrate JA , Tijburg LB . Bioavailability of catechins from tea: the effect of milk . Eur J Clin Nutr . 1998;52:356-359.
61. Briggs G , Freeman RK , Yaffe SJ . Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk . 3rd ed. Baltimore, MD: Williams and Wilkins; 1990.
62. Taylor JR , Wilt VM . Probable antagonism of warfarin by green tea . Ann Pharmacother . 1999;33:426-428.
63. Nelson M , Poulter J . Impact of tea drinking on iron status in the UK: a review . J Hum Nutr Diet . 2004;17:43-54.
64. Ullmann U , Haller J , Decourt JD , Girault J , Spitzer V , Weber P . Plasma-kinetic characteristics of purified and isolated green tea catechin epigallocatechin gallate (EGCG) after 10 days repeated dosing in healthy volunteers . Int J Vitam Nutr Res . 2004;74:269-278.