Camellia sinensis

Green tea

Description

Tea ranks second only to water as a major component of fluid intake worldwide and has been considered a health-promoting beverage since ancient times. The history of tea began over 5000 years ago in ancient China. Currently, tea is the most popular beverage consumed by two-thirds of the world's population. Green tea, black tea, and Oolong tea are all derived from the leaves of Camellia sinensis. To produce green tea, freshly harvested leaves are steamed to prevent fermentation, yielding a dry, stable product. To produce black tea, the fresh leaves are allowed to wither, and then rolled and crushed, initiating fermentation of polyphenols. Oolong tea is produced by a partial oxidation of the leaf, intermediate between the process for green and black tea. Among all teas consumed in the world, green tea is the most studied for its health benefits, including cancer prevention. It is noteworthy that tea polyphenols are considered to contribute to the prevention of various other degenerative diseases like cardiovascular diseases, arthritis and diabetes.1 About 20% of the world tea production is consumed as green tea.

Constituents

Tea polyphenols, known as catechins, account for 30–42% of the dry weight of the solids in brewed green tea. Belonging to the flavan-3-ol class of flavonoids, major catechins found in tea leaves are epigallocatechin-3-gallate (EGCG), epigallocatechin (EGC), epicatechin-3-gallate (ECG) and epicatechin (EC). Catechin, gallocatechin, epigallocatechin digallates, epicatechin digallate, 3-O-methyl EC and EGC, catechin gallate, and gallocatechin gallate are present in smaller quantities. Flavonols, including quercetin, kaempferol, myricitin, and their glycosides are also present in tea. A typical tea beverage, prepared in a proportion of 1 g leaf to100 ml water in a 3-min brew, usually contains 250–350 mg tea solids, comprised of 30–42% catechins and 3–6% caffeine.1

Therapeutic activities

Antioxidant

Green tea polyphenols are good antioxidants and has been shown to inhibit free radical lipid peroxidation in vitro, in human red cells, in human low density lipoprotein, and in rat liver microsomes. Green tea interacts with α-tocopherol (vitamin E) and ascorbic acid synergistically to enhance their antioxidant activity.2

Anticancer

Green tea inhibits cancer in a variety of ways:1

Action Notes
Modulation of transduction pathways Green tea modifies the activities of various receptor tyrosine kinases and particular pathways of signal transduction, thereby altering the expression of genes involved in cell proliferation, angiogenesis, and apoptosis.
Inhibition of mitogen activated protein (MAP) Activation of MAP activates various transcription factors leading to changes in the expression of genes that play critical roles in cell proliferation, migration and apoptosis.
Inhibition of nuclear factor-ƘB NF-ƘB is a transcription factor involved in the inflammatory and innate immune responses
Inhibition of epidermal growth factor receptor (EGFR) EGFR is a transmembrane glycoprotein with intrinsic tyrosine kinase activity that regulates cell proliferation and differentiation. EGFR is expressed by various epithelial tumours and its high levels of expression in these cells indicate a poor prognosis or a late stage of disease.
Inhibition of insulin-like growth factor (IGF)-I The IGF pathway comprises a complex system of molecules involved in regulation of a diverse array of normal and pathological biological functions. The IGF is a complex system of peptide hormones, cell surface receptors and circulating binding proteins. IGF-1 and -2 are mitogens that play a role in regulating cell proliferation, differentiation and apoptosis.
Inhibition of proteasome activities The proteasome is a multi-catalytic enzyme which is an important component of a complex pathway that targets and destroys intracellular proteins. These proteins have various functions including regulation of the cell cycle, protection from apoptosis, and transcriptional regulation. The proteasome regulates cell growth, survival, and metastasis of cancer cells.
Inhibition of matrix metalloproteinases (MMPs) Tumour invasion and metastasis is a multistep process that involves proteolytic degradation of the ECM, alteration of the cell–cell and cell–ECM interactions, and migration of the cancer cell through the basement membrane. The matrix metalloproteinase (MMP) enzymes are capable of degrading various components of the extracellular matrix (ECM) and may cause inflammatory, vascular, autoimmune disorders, and carcinogenesis.
Inhibition of urokinase-plasminogen activator (uPA) uPA is primarily associated with the degradation and regeneration of the basement membrane and extracellular matrix that leads to metastasis. It also aids in anti-thrombolytic activities to remove blood clots and helps stimulate angiogenesis in tumour cells.
Induction of apoptosis and cell cycle arrest EGCG induces apoptosis and cell cycle arrest in many cancer cells including lung, colon, pancreas, skin, and prostate without affecting normal cells.

Anti-fibrotic

Epigallocatechin gallate (EGCG) has anti-fibrotic properties in many organs. EGCG has been shown to reduce hepatic fibrosis, by inhibiting activation and proliferation of hepatic stellate cells, interrupting transformation growth factor-beta (TGF-β) signalling and suppressing collagen production and collagenase activity. Chronic pancreatitis is a progressive and irreversible disease, with intractable pain and loss of pancreatic exocrine and endocrine function. Pancreatic stellate cells play a major role in pancreatic fibrosis. After injury, they are activated and transformed into myofibroblast-like cells which synthesise and secrete increased amounts of extracellular matrix. TGF-β 1 is a major mediator of fibrosis in pancreatic fibrosis. EGCG has been shown to reduce chemically induced pancreatic fibrosis in rats by 28-66% compared to controls. EGCG inhibited overexpression of TGF-b 1 and of smooth muscle actin (a symbol of activation of pancreatic stellate cells). Moreover, EGCG has a potent influence on expression of Smads (downstream transcription factor of TGF-b 1).3

Anti-inflammatory

EGCG inhibits a variety of inflammatory mediators including IL-1 beta-induced expression of matrix metalloproteinases and mitogen activated protein kinases. EGCG also inhibits the IL-1 beta-induced activity and expression of cyclooxygenase-2 (COX-2) and nitric oxide synthase-, as well as the production of nitric oxide.4, 5 Green tea has also been shown to inhibit cartilage proteoglycan and collagen degradation in vitro6 and to reduce the expression of inflammatory mediators such as cyclooxygenase 2, IFN-gamma, and tumour necrosis factor alpha in arthritic joints in vivo.7

Cardiovascular effects

Tea consumption is associated with decreased cardiovascular risk. Catechins may prevent cardiovascular diseases by preventing LDL from oxidative damage by free radical quenching and metal chelating abilities, or by recycling other antioxidants such as vitamin E. Catechins appear to interfere with several stages of the inflammatory process involved in atherosclerosis and may influence haemostatic indexes and reduce thrombosis. In vitro studies found green tea inhibits thromboxane8; platelet aggregation9; and LDL oxidation10, suggesting cardio-protective effects.11

Research suggests that black tea improves short and long-term endothelial performance, but green tea has been shown to also have a short-term beneficial effect on the large arteries. Using ultrasound scanning green tea was shown to dilate the brachial artery. Dilation of an artery shows better functioning of the endothelium, the layer of cells lining blood arteries, making the artery less susceptible to thrombosis. 14 healthy volunteers (aged 30+/-3 years) with no cardiovascular risk factors except from smoking (50%) were given green tea, caffeine or hot water to drink on three separate occasions (6 g of green tea, 125 mg of caffeine (the amount contained in 6 g of tea). Measurements of the brachial artery were taken at three stages after they drank their beverage. The researchers found the artery expanded by nearly 4% (p<0.02) 30 minutes after volunteers drank green tea. Caffeine or hot water had no effect.12 Green tea has also been shown to reduce aortic stiffness.13

Metabolic

A green tea extract has been shown to inhibit gastric and pancreatic lipases and stimulate thermogenesis.14

Human studies

Hyperlipidaemia

Preliminary research suggests green tea has beneficial effects on blood lipids in individuals with hypercholesterolemia. In a randomised controlled trial of 240 moderately hypercholesterolemic participants, the effect of a theaflavin-enriched green tea extract on plasma lipids was examined. All patients were on a low-fat diet. Patients were randomly assigned to receive a daily capsule containing theaflavin-enriched green tea extract (375mg) or placebo for 12 weeks. Main outcome measures were mean percentage changes in total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglyceride levels compared with baseline. After 12 weeks, the mean changes from baseline in total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglyceride levels were -11.3% +/- 0.9% (p=.01), -16.4% +/- 1.1% (p =0.01), 2.3% +/- 2.1% (p=0.27), and 2.6% +/- 3.5% (p=0.47), respectively, in the tea extract group. The mean levels of total cholesterol, LDL, HDL, and triglycerides did not change significantly in the placebo group. No significant adverse events were observed. It was concluded that the theaflavin-enriched green tea extract was effective as an adjunct to a low-saturated-fat diet to reduce LDL-cholesterol in hypercholesterolemic adults.15

Preliminary research suggests green tea decreases postprandial triglyceride levels in individuals with hypertriglyceridemia. The effects of tea catechins on postprandial plasma lipid responses in individuals with mild hypertriglyceridemia was tested in a randomised triple-crossover design involving nine male subjects who consumed 10 mg (control), 224 mg (moderate dose) and 674 mg (high dose) of the assigned tea catechins three times daily along with a standardised light meal consisting of a piece of bread spread with 20 g butter. Plasma lipids were measured in the fasting state and one, two, three, four and six hours after consuming the light meal. Results showed that, compared with the control, moderate and high doses of tea catechins significantly reduced the incremental area under the plasma triacylglycerol curves by 15.1 and 28.7%, respectively. The rapid elevation of remnant-like particle cholesterol was significantly inhibited by a high dose of tea catechins two hours after consuming the light meal (p<0.01). No significant differences were observed in the postprandial responses for plasma total cholesterol or free fatty acids.16

However, in healthy, male volunteers, 600 mL green tea daily for four weeks, resulted in no significant change in the lipid profile, levels of C-reactive protein, or levels of soluble intercellular adhesion molecule-1 (sICAM-1), or soluble E-selectin (an early mediator of leukocyte-endothelial adhesion).17

Weight loss

Green tea has thermogenic properties and promotes fat oxidation beyond that explained by its caffeine content. Green tea extract may play a role in the control of body composition via sympathetic activation of thermogenesis, fat oxidation, or both. There have been several studies on green tea and weight loss. Green tea has been shown in earlier studies to improve weight loss when subjects are following a low or balanced energy diet; however the weight loss and reduction in waist circumference has only been modest.18, 19, 20 Furthermore, a randomised, double-blind, placebo-controlled clinical trial found that green tea did not statistically reduce BMI or weight in 78 obese women aged between 16 and 60 years with BMI > 27 kg/m2.21

However, a recent randomised, controlled trial conducted in Thailand found that green tea did help reduce both the BMI and the weight in obese subjects (body mass index, BMI 25kg/m2). All subjects consumed a Thai diet containing 3 meals (8374 kJ/day) for 12 weeks, prepared by a Hospital Nutritional Unit. The diet contained 65% carbohydrates, 15% protein, and 20% fat. The patients received a 250 mg green tea or placebo capsule after breakfast, lunch, and dinner. Green tea produced a significant weight loss and increase in resting energy expenditure. At the 8th and 12th weeks of the study, body weight loss was significantly different (p <0.05). At the 8th week the resting energy expenditure had significantly increased (p < 0.001). The BMI decreased from 27.4 to 24.9 at week 8 (p<0.001) and to 24.45 at week 12 (see figures 1 and 2).

Camellia sinensis - figure 1
Figure 1: Green tea induced weight loss.

Camellia sinensis - figure 2
Figure 2: Green tea induced reduction in BMI.

No significant differences existed in satiety score, food intake, or physical activity. The authors concluded that green tea can reduce body weight in obese Thai subjects by increasing energy expenditure and fat oxidation.22

Cancer

A prospective cohort study over 10 years in Japan showed that the daily consumption of green tea delayed the onset of cancer in both smokers and non-smokers.23 Daily consumption of green tea in a prospective cohort study with over 8000 individuals resulted in delayed cancer onset, and a follow-up study of breast cancer patients found that stages I and II breast cancer patients experienced a lower recurrence rate and longer disease-free period.24

Prostate cancer

A study found that green tea capsules have been shown to inhibit the conversion of high-grade prostate intraepithelial neoplasia (PIN) lesions to cancer. After one year, the incidence of prostate cancer in men given green tea catechins capsules was 3%, compared to 30% incidence in the placebo-treated men.25 Evidence from a case-control study conducted in China assessing 130 patients with histologically confirmed incidental prostate cancer and 274 patients without cancer matched by age, showed that the prostate cancer risk declined with increasing frequency, duration and quantity of green tea consumed. This reduction was statistically significant, suggesting that green tea protects against prostate cancer.26 In the Japan Public Health Centre-based Prospective Study, 49,920 men aged 40– 69 years completed a questionnaire that included their green tea consumption habit. Green tea was not associated with localised prostate cancer. However, consumption was associated with a dose-dependent decrease in the risk of advanced prostate cancer.27

Breast cancer

In a case control study, conducted in China on 1009 female patients aged 20–87 years with histologically confirmed breast cancer, green tea consumption was found to be associated with a reduced risk of developed breast cancer.28 A study of fifty women found that green tea intake was inversely correlated with serum concentrations of oestradiol on menstrual cycle day 11. This alteration of hormone levels was associated with a decreased risk for developing breast cancer.29 Other studies have supported these results, and have suggested that consumption of green tea prior to clinical cancer onset is significantly associated with improved prognosis of state I and II breast cancer.30 A recent meta-analysis showed that the combined results of green tea consumption from four studies showed a reduced risk of breast cancer for highest versus lowest intake groups.31

Cervical cancer

EGCG (200 mg orally for 12 weeks) has been reported to be effective in the patients with human papilloma virus (HPV) infected cervical lesions.32

Actions

Antioxidant, anticancer, anti-fibrotic, anti-hyperlipidaemic, anti-inflammatory, anti-platelet, cardioprotective, thermogenic.

Traditional usage

Green tea is used in Traditional Chinese Medicine as an astringent, cardiotonic, central nervous system stimulant, and diuretic. It may be used for treating flatulence, for regulating body temperature, promoting digestion, and improving mental processes. In India, green tea has additionally been used to treat fungal infections. Green tea bags have also traditionally been used topically to soothe sunburn, headache, tired eyes, and to stop bleeding of the gums or tooth sockets.33

Indications

  • Cancer prevention, prevention of recurrence
  • Cardiovascular diseases, hyperlipidaemia, hypercholestrolaemia, reducing atherosclerosis and thrombosis
  • General antioxidant therapy
  • Weight loss
  • Fibrosis of pancreas and liver
  • General anti-inflammatory therapy for arthritis and other inflammatory diseases

Use in pregnancy

Precautions and contraindications of green tea related to pregnancy and lactation are predominantly theoretical and based upon the adverse effect profile of caffeine.

Contraindications and cautions

Traditionally, green tea is consumed throughout the day in Asian countries and is considered safe and nontoxic. Green tea may contain up to 50 mg of caffeine per cup. Excessive intake of 500 mg of caffeine (10 cups) per day both short-term and long-term adverse effects are possible. Some green tea extracts are decaffeinated, a process that should not alter the polyphenol levels.

Administration and Dosage

Green tea is traditionally consumed an average of three cups per day (total polyphenol content of 240-320 mg per day). For medicinal purposes, dosages may be as high as 10 cups daily.

Cancer

A study has shown that daily consumption of the equivalent of two or three cups of green tea reduced the risk for oesophageal cancer among non-smokers/non-drinkers of alcoholic beverages.34 On the other hand, studies in Japan suggest that 10 cups of green tea is cancer-preventive.35

Dosage

Green Tea (1:1) leaf extract: 1.0 to 3.0 ml 3 times daily.

References

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  2. Dai F, Chen WF, Zhou B Antioxidant synergism of green tea polyphenols with α-tocopherol and l-ascorbic acid in SDS micelles Biochimie, 2008;90(10): 1499-1505
  3. Meng M, Li YQ, Yan MX, Kou Y, Ren HB.Effects of epigallocatechin gallate on diethyldithiocarbamate-induced pancreatic fibrosis in rats.Biol Pharm Bull. 2007 Jun;30(6):1091-6.
  4. Ahmed, S., Rahman, A., Hasnain, A., Lalonde, M., Goldberg, V. M., and Haqqi, T. M. Green tea polyphenol epigallocatechin-3-gallate inhibits the IL-1 beta-induced activity and expression of cyclooxygenase-2 and nitric oxide synthase-2 in human chondrocytes. Free Radic.Biol Med 10-15-2002;33(8):1097-1105
  5. Singh, R., Ahmed, S., Islam, N., Goldberg, V. M., and Haqqi, T. M. Epigallocatechin-3-gallate inhibits interleukin-1beta-induced
    6. expression of nitric oxide synthase and production of nitric oxide in human chondrocytes: suppression of nuclear factor kappaB activation by degradation of the inhibitor of nuclear factor kappaB. Arthritis Rheum 2002;46(8):2079-2086.
  6. Adcocks, C., Collin, P., and Buttle, D. J. Catechins from green tea (Camellia sinensis) inhibit bovine and human cartilage proteoglycan and type II collagen degradation in vitro. J Nutr 2002;132(3):341-346
  7. Haqqi, T. M., Anthony, D. D., Gupta, S., Ahmad, N., Lee, M. S., Kumar, G. K., and Mukhtar, H. Prevention of collagen-induced arthritis in mice by a polyphenolic fraction from green tea. Proc Natl.Acad.Sci U.S.A 4-13-1999;96(8):4524-4529.
  8. Ali, M., Afzal, M., Gubler, C. J., and Burka, J. F. A potent thromboxane formation inhibitor in green tea leaves. Prostaglandins Leukot.Essent.Fatty Acids 1990;40(4):281-283.
  9. Sagesaka-Mitane, Y., Miwa, M., and Okada, S. Platelet aggregation inhibitors in hot water extract of green tea. Chem Pharm Bull.(Tokyo) 1990;38(3):790-793
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  16. Unno, T., Tago, M., Suzuki, Y., Nozawa, A., Sagesaka, Y. M., Kakuda, T., Egawa, K., and Kondo, K. Effect of tea catechins on postprandial plasma lipid responses in human subjects. Br J Nutr 2005;93(4):543-547.
  17. Sung, H., Min, W. K., Lee, W., Chun, S., Park, H., Lee, Y. W., Jang, S., and Lee, D. H. The effects of green tea ingestion over four weeks on atherosclerotic markers. Ann.Clin Biochem 2005;42(Pt 4):292-297
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  32. Ahn, WS., Yoo, J., Huh SW., Kim, CK., Lee, JM., Namkoong NE. et al., Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions, Eur.J. Cancer Prev. 2003;12: 383–390.
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