Biological Actions And Medicinal Applications Of Tea (Camellia Sinensis)Correspondence Address :
Thakuria N,Dept of Pharmacology,Assam MedicalCollege&Hospital Dibrugarh,Assam,Pin:786002(India)Ph:+91-9435702938E-mailâ€“email@example.com
Tea, Flavonoids, Antioxidant, Cardiovascular Diseases, Cancer, Cognitive Function
Tea is an aqueous infusion of dried leaves of the plant Camellia sinensis (family Theaceae) and is the most popular beverage consumed by human society worldwide. Per-capita consumption worldwide averages 4 fluid ounces per day. Tea was discovered in China around 5000 to 6000 years ago (1).
Depending on the manufacturing process tea is classified into three major types (Table/Fig 1):-
â€˘ Green (unfermented)
â€˘ Oolong (fermented)
â€˘ Black (fully fermented)
About 76% to 78% of tea produced and consumed worldwide is black tea, 20% to 22% green and less than 2% is oolong (2).
Tea is a rich source of polyphenols, particularly flavonoids. The major group of flavonoids present in tea is catechins. Principal catechins present in fresh tea leaves are (-)-epicatechin (EC), (-)-epigallocatechin (EGC) and (-)-epigallocatechin-gallate (EGCG)(Table/Fig 2). EGCG is the most abundant catechin in tea leaves of most green, oolong and black teas (1). Green and oolong teas contain 30 to 130 mg of EGCG per cup (237 ml), while black tea may contain 0 to 70 mg of EGCG per cup (3).
The type of processing applied to the fresh tea leaves determines the type and amount of flavonoids present in different types of tea.
During the production of oolong tea, the oxidation period is shortened, resulting in partially oxidized and containing more catechins and fewer theaflavins and thearubigins than black tea (1),(5).
In addition to polyphenols, tea also contains glycosides of flavonol, proanthrocyanidines, caffeine, amino acids (mostly theanine), carbohydrates (glucose, fructose, sucrose etc.), organic acids (di-carboxylic acid, tri-carboxylic acid and fatty acids), saponins, pigments (chlorophyll, carotinoids and others), vitamins (rich in vitamin C also B-complex, E & K), soluble minerals and C, H, N, O, Ph and K, cellulose, lignins, polysaccharides, lipids, insoluble pigments and organic compounds like hydrocarbons, alcohols, aldehydes, ketones, acids, esters, lactones, phenolic compounds, nitrogen compounds, oxygenated compounds and sulphur compounds (6).
Health Benefits Associated With Tea And Its Components
It has been known for a long time that tea may exert a number of physiological effects on human body. Numerous epidemiological studies and clinical trials examining the relationship between tea and its health benefits have proven the same and still many such studies are underway. In this review, we have assessed few recent clinical studies of tea on health and disease in humans.
Antioxidant Activity Of Tea
The role of free radicals and active oxygen in pathogenesis of a number of chronic diseases including cardiovascular diseases, cancer, neurodegenerative diseases and ageing process has been recognized. Green tea is rich in polyphenlos (catechins and gallic acid, particularly), but it also contains carotenoids, tocopherols, ascorbic acid (vitamin C), minerals such as Cr, Mn, Se or Zn, and certain phytochemical compounds.
Using the Oxygen Radical Absorbance Capacity (ORAC) assay, Cao et al. (7) found that both green and black tea have much higher antioxidant activity against peroxyl-radicals than vegetables such as garlic, kale, spinach and Brussels sprouts. Langley-Evans (8) determined the antioxidant potential of green and black tea by using Ferric Reducing Ability of Plasma (FRAP) assay and found that the total antioxidant capacity of green tea was more than black tea. Nanjo et al. (9) using Tocol Equivalent Antioxidant Capacity (TEAC) assay, found catechins to be more effective scavengers of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical than vitamin E or vitamin C. Relative activities of catechins in scavenging DPPH radicals have been found to be EGCG ≈ ECG > EGC > EC (10), (11).
The concentration of phosphatidylcholine hydroperoxide (PCOOH), an index of lipid peroxidation, was found to be decreased by 69%, decreasing copper mediated antioxidation of plasma 60 minutes after consumption of a green tea extract tablet containing EGCG: 82mg, ECG: 38mg, EGC: 27 mg and GCG: 37mg (12). Fe-isoprostanes are established biomarkers for in vivo oxidative stress and have been shown to correlate with conditions of increased lipid peroxidation in animals and humans. Frease R et al. (13) found a significant 22% reduction in plasma TBARs in 20 healthy women of 23 to 50 years of age consuming high linoleic acid diet and administered with green tea extract 3gm/day (equivalent to 10 cups/day of green tea) for 4 weeks; however, no change in urinary levels of 8-iso-PGF2, an F2-isoprostane were found.
Topical EGCG was found to significantly reduce UV induced TBAR formation, H2O2 and Nitrate formation in skin (p < 0.05) after UV light exposure (14). In a study on 10 Type-2 diabetes mellitus patients consuming a high flavonoid diet, including six cups of black tea daily for two weeks was found to reduce the oxidative damage to lymphocyte DNA significantly (15). In another study on smokers it was found that drinking 900ml green tea daily for 7 days reduced 8-OH-dG in urine and WBC nuclear DNA (16). Erba et al. (17) suggest the ability of green tea, consumed within a balanced diet, to improve the overall antioxidative status and to protect against oxidative damage in humans.
Effects Of Tea On Cardio Vascular System
The physiological effects of tea and tea products on cardiovascular system and their potential uses for prevention and treatment of disorders of cardiovascular system have drawn a great deal of interest.
It is one of the most commonly occurring cardiovascular disorders and may induce many serious complications. Association of tea consumption with severity of aortic atherosclerosis was examined in 3454 men and women, 55% of them had some degree of aortic atherosclerosis on X-ray. Calcified plaques in the abdominal aorta were detected radiographically after 2-3 years of follow-up. The risk of aortic atherosclerosis for black tea drinkers was 54% for those who drank 1-2 cups/day (≤ 250ml/day), 47% for those who drank 3-4 cups/day (> 250-≤ 500ml/day) and 35% for those who drank more than 4 cups/day (> 500ml/day) (18) when compared to non-drinkers.
An observational study by Sasazuki et al. (19) on men and women undergoing coronary angiography reported an inverse relation of green tea consumption to coronary artery disease in men but not in women. Endothelial dysfunction is associated with atherosclerosis. Consumption of black tea reverses endothelial dysfunction in patients of CHD (20) and hyperlipidemia (21). Weon Kim et al (22) observed that the number of circulating Endothelial Progenitor Cells (EPCs) and flow-mediated endothelium dependent vasodilation (FMD) was reduced in chronic smokers. A short-term therapy of green tea consumption was found to induce a rapid improvement of EPC levels and FMD and they concluded that green tea consumption might be effective in preventing future cardiovascular events in chronic smokers. Catechin is a major constituent of Japanese green tea and an antioxidant. Lipids and oxidization of low-density lipoprotein cholesterol (LDL-C) play important roles in atherosclerosis. Shigenobu et al (23) documented a novel observation, that cathechins decrease the plasma Ox-LDL concentration without any significant change in plasma LDL concentration. The beneficial effects of green tea on coronary artery disease might result from a decrease in plasma Ox-LDL.
Yang et al. (24) concluded that habitual moderate strength green tea or oolong tea consumption, 120 mL/day or more for 1 year significantly reduces the risk of developing hypertension in Chinese population. Nakachi et al. (25) in a prospective cohort study of 8522 men and women concluded that consuming 10 cups/day is linked with a decreased relative risk (RR) of death from cardiovascular disease in men (RR _ 0.58, 95% CI _ 0.34â€“0.99) and women (RR _ 0.82, 95% CI _ 0.49â€“1.38).
Coronary Heart Disease
Several studies indicate an inverse association between tea consumption and coronary heart disease (CHD) mortality.
A cohort study of 8522 Japanese men and women for a period of 13 years found a significant reduction in the risk of death from CHD among men consuming more than 10 cups (1500ml) of green tea, although they failed to find significant reduction of risk in women (26). Geleijnse et al. (27) in their prospective Rotterdam study with 3454 adults, 55 years of age or older, and with a follow-up duration ranging from two to three years, examined aortic atherosclerosis via X-ray measurement of calcified deposits in abdominal aorta. The odds ratio (OR) for drinking 125â€“250 mL (1â€“2 cups) of black tea daily was 0.54 (95% CI _ 0.32â€“0.92) and decreased to 0.31 (95% CI _0.16â€“0.59) when _500 mL/day (more than four cups) were consumed.
Hertog et al. (28) by conducting a cohort study of 804 men in Netherlands found an inverse association between flavonoid intake and CHD mortality. In this study black tea was the source of 60-80% of total dietary flavonoids.
However, several studies didnâ€™t find any significant relationship between tea consumption and CHD mortality. Rimm et al. (29) employing a cohort of 34,789 men in US followed up for 2 years, reported no significant reduction in the risk of death from CHD mortality, for those consuming > 2 cups of black tea/day. Yokozawa et al. (30) reported that administration of GTP effectively inhibited LDL-cholesterol oxidation and elevated serum antioxidative activity.
Effects On Blood Lipid
Excessive lipid in blood is a common disorder of middle aged and old aged men and women. Several epidemiological studies show that tea drinking decreases serum lipid levels in a large population. Imai et al. (31) conducted a cross sectional study on 1371 Japanese men aged 40 years or more and found that consumption of green tea was associated with significantly lower levels of serum lipid and LDL. Dietary antioxidants may slow atherogenesis by reducing the oxidative modification of LDL cholesterol (32). Several in vitro studies to isolate LDL have shown inhibition of lipid oxidation by tea and tea extracts (33), (34), (35). However, in vivo studies in humans found little or no inhibition of LDL oxidation. Miura et al. (36) also found an increase in lag time among 22 healthy young men after consumption of green tea extract equivalent to 700ml/day (7-8 cups/day) of green tea for 1 week.
Cancer is a serious health problem and cause of global concern. Experimental studies have demonstrated the inhibitory effect of tea infusions and its components, specially, polyphenols on chemical carcinogenesis of various cancers in experimental animals. The chemopreventive effects of green tea depend on: (1) its antioxidant action; (2) specific induction of detoxifying enzymes; (3) its molecular regulatory functions on cellular growth, development and apoptosis; and (4) selective improvement in function of intestinal bacterial flora. An important aspect of cancer risk is related to inflammatory response; currently, antiinflammatory agents are used in chemopreventive strategies. The inflammatory response involves production of cytokines and proinflammatory oxidants such as hypochlorous acid and peroxynitrite produced by neutrophils. Green tea catechins and soy isoflavones have also been shown to be chemopreventive. The aromatic nature of polyphenols makes them potential targets of hypochlorous acid and peroxynitrite, and these reactions may create novel pharmacophores at the site of inflammation. In addition, a major mechanism of the anticarcinogenic activity of green tea in animals is impairment of interaction of carcinogens with DNA leading to mutations.
Gao et al. (38) in a case control study found an inverse relationship between tea consumption and oesophageal cancer. They observed that Chinese women who consumed atleast 150 gm/month of green tea were 66% less likely to have oesophageal cancer than women who did not drink tea. Another study in South America by Castellsague et al. (39) reported that men and women who consumed more than 500ml/day of tea were 38% less likely to have oesophageal cancer than those who did not drink tea.
Several studies have shown inverse association between tea consumption and sto-mach cancer. A prospective cohort study conducted by Zhang W et al. (40) on 1,20,852 people in Netherlands found an inverse relationship between black tea and stomach cancer. Another study by Shibata et al. (41) among 636 Japanese in green tea production village observed that consumption of 10 cups of green tea/day reduced the risk of stomach cancer. In contrast, Heilbrun et al. (42) in a cohort study of 7,833 men followed for a period of 20 years in Hawaii, USA did not find any significant association between black tea consumption and gastric cancer risk. On the other hand, Hamajima et al. (43) found that an equivalent of ten cups a day of green tea polyphenols for one year was no more effective than one to two cups a day in improving serum pepsinogen levels (reflecting stomach atrophy), a risk factor for stomach cancer. Sasazuki et al. (44) reported an inverse association between green tea consumption and distal gastric cancer among women; however, these authors indicated that more prospective studies with detailed information were needed to confirm the role of green tea in occurrence of gastric cancer.
Several experimental studies indicate strong chemopreventive action of tea and tea flavonoids against cancers of gastrointestinal tract, particularly colorectal cancers. In a cohort study of 7,833 men in USA, Heilbrun et al. (42) found a positive association between rectal cancer and black tea consumption. In the same study, they also found no significant association with colon cancer. Another prospective study of 29,133 male smokers in Finland, found a positive association of black tea consumption and colon cancer (> 1 cup vs. 0 cup); in the same study, no significant association was found with occurrence of rectal cancer (45).
Interestingly, green tea polyphenols have been found to reduce prostaglandin E2 synthesis in rectal mucosa by 50% within four hours of consumption (47).
Shibata et al. (48) have reported an inverse association between intake of black tea and pancreatic cancer in a cohort study on 13,979 elderly men and women in USA. In contrast, earlier studies show no chemoprotective action by black tea on pancreatic cancer (6, 47,282).
A case control study by Mendilaharsu et al. (49) found that consumption of 2 or more cups of black tea reduced the risk of lung cancer by 66% in male smokers in Uruguay. In a cohort study of 58,279 men and 62,573 women in the Netherlands (46) and two cohort studies of 7,533 men and 35,369 post-menopausal women respectively, in USA showed no chemopreventive action by black tea on lung cancer. Laurie SA et al (50) in a Phase I study of green tea extract in patients with advanced lung cancer observed an inverse correlation of lung cancer with green tea consumption.
Urinary Bladder Cancer
A case control study on 4,000 Americans by Bianachi et al. (51) reported that consumption of more than 5 cups of tea a day reduced the risk of bladder cancer by 30%. Significant reduction in risk of bladder cancer was found in a prospective cohort study among 3,123 men and women after 6 years follow-up in Netherlands, who drank more than 2 cups of black tea (52). Conversely, Nagano et al. (53) reported no significant association of tea (both black and green) intake and bladder carcinoma in a prospective cohort study of 38,450 Japanese atomic bombs survivors. In a follow-up study of this cohort, Wakai et al. (54) found that patients who drank green tea had a substantially better five-year survival rate than those who did not.
Heilbrun et al. (42) in a cohort study of 7,833 Hawaiian men of Japanese descent found a significant inverse association between black tea consumption and prostate cancer risk. Jain et al (55) reported 30% reduction in the risk of prostate cancer, in those who drank >500 ml/day of black tea in a case control study of 1,254 Canadians. In vitro, tea inhibits 5-α-reductase mediated conversion of testosterone to 5-α-dihydrotestosterone which suggests a potential mechanism of action in prostate cancer (56).
However, no association between tea intake and prostate cancer was observed in a retrospective cohort study of 1970â€“1972 Nutrition Canada Survey participants. In this study, subjects who drank 500 mL of tea per day, experienced the same risk for prostate cancer as compared to those who reported no tea consumption (RR-1.02, 95% CI: 0.62â€“1.65) (57). Although, these observations are most relevant to black tea, a worth noting evidence by Paschka et al. (58) reports that green tea catechin EGCG induces apoptosis in human prostate cancer cells. In same line of research, Yu et al. (59) reported that EGCG inhibits growth of prostate cancer adenoma cells and induces apoptosis. Dose-response relationships were also significant, suggesting that green tea is protective against prostate cancer.
In a cohort study, Rosenberg et al. (60) found an inverse association between black tea consumption and breast cancer. Consistent with these data, a Japanese study of 472 stage I & II breast cancer patients, found an inverse correlation between consumption of green tea and rate of recurrence after 7 years. Recurrence rate was 16.7% for patients consuming 5 or more cups a day vs. 24.3% for those drinking 4 or less a day. Green tea may favourably alter oestradiol and sex hormone binding globulin levels associated with risk of breast cancer (61).
In contrast to these observations, two cohort studies, one in Netherlands on 62,573 men (46) and another in USA (42) on 35,369 post-menopausal women found no chemo-preventive action of consumption of more than 4 cups/day of black tea. The relative risk of recurrence was 0.564 (95% CI: 0.350â€“0.911) and recurrence rate was 16.7% for patients consuming five or more cups a day versus 24.3% for those drinking
Mittal et al. (37) reported that treatment with EGCG decreases cell viability at different stages studied (approx. 80% inhibition) in human breast carcinoma MCF-7 cells, but had no adverse effect on growth of normal mammary cells. These authors found that this treatment inhibited telomerase activity (40â€“55%); telomerase is elevated in 90% of breast carcinomas and therefore has received much attention as a target for breast cancer therapy and cancer diagnostic research. Two studies in Japanese women diagnosed with breast cancer indicate that green tea consumption is inversely associated with rate of recurrence, especially in early stages of breast cancer (62), (63).
Several experimental studies indicate a protective effect of tea polyphenols against chemical and ultraviolet (UV)-induced skin cancer. Hakim et al. (64) reported an inverse association between black tea consumption and occurrence of squamous cell carcinoma of skin in a population based case control study of 450 older adults in Arizona. Katiyar et al. (65) reported that topical application of EGCG (1mg/cm square) inhibits UVB induced infiltration of leucocytes and subsequent generation of reactive oxygen and nitrogen species in animal and human skin as well as prevented UV-induced decrease in skin GPX activity and GSH levels. Zhao et al. (66) reported the topical application of a standardized green tea extract 30 minutes prior to administration of psoralen plus UVA radiation to reduce the photochemical damage associated with this treatment for psoriasis.
Li et al. (67) conducted a double-blind, placebo-controlled trial in 59 patients with oral mucosa leukoplakia, a pre-cancerous lesion, and found oral and topical administration of black and green tea mixture to partially regress the lesion in 37.9% of treated patients.
In 1981, Onisi et al. (68) conducted a clinical test of effect of drinking green tea extract on dental caries at a primary school for an year. Incidence of dental caries among children who took a cup of tea immediately after lunch was found to be significantly lower. Ooshima et al. (69) investigated the inhibitory effect of Oolong tea extract (OTR- containing 40% polyphenolic compounds) on plaque deposition in 35 human volunteers and found that mouth rinsing with 0.5 mg/ml OTE in 0.2% ethanol significantly reduced plaque deposition when compared with mouth rinsing with 0.2% ethanol (p<0.001).
Rasheed et al. (70) reported that extract of green tea inhibits oral bacteria such as E. coli, Streptococcus salivarius and streptococcus mutans. Mutans streptococci is the primary pathogen responsible for producing caries. These bacteria synthesize extracellular water insoluble glucans on surface of organisms by glucosyl transferase from sucrose. These glucans adhere to tooth surface resulting in formation of dental plaques. Matsumoto et al. (71) reported decreased adherence to tooth surface by reducing the hydrophobicity of streptococci and to inhibit their carcinogenicity by reducing the rate of acid production.
Tea consumption was identified as an independent factor protecting against risk of hip fractures in women and seven men, over the age of 50 years in the Mediterranean Osteoporosis Study (72), (73). Consistent with this observation, Hegarty et al. (74) studied 1,256 British women, 65 to 76 years of age, and found that those who drank tea had greater bone mineral density than those who did not drink tea. Higher mean bone mineral density of the lumbar spine (p _ 0.004), greater trochanter (p _ 0.004) and Wardâ€™s triangle (p _ 0.02) were independent of smoking status, hormone replacement therapy, coffee drinking and addition of milk to tea.
A case control study of 215 Parkinsonâ€™s disease patients and 312 controls in Taiwan by Chan et al. (75) observed that regular tea drinking had protective effect against the disease. Flavonoid intake was inversely related to risk of dementia in a French cohort in which tea provided only 16 % of total flavonoid intake (76). Hindmarch et al. (77) reported that day long consumption of tea improved cognition and psychomotor performance of healthy adults.
Advanced glycation endproducts (AGEs) are believed to be secondary factors in selective neuronal injury associated with several neurodegenerative disorders. Sun-joo Lee et al (78) demonstrated that EGCG may exhibit protective effects against AGE induced injury in neuronal cells through its antioxidative properties, as well as by interfering with AGEs-RAGE interaction mediated pathways, suggesting a beneficial role for this catechin against neurodegenerative diseases.
Duchenne Muscular Dystrophy
Olivier M. Dorchies et al (79), through a pre-clinical study in mice concluded that green tea extract (GTE) polyphenols behave as multitarget agents that are capable of positively altering several of the downstream consequences of dystrophin absence.
Narayanan Sriram et al (80) confirmed through a pre-clinical study in rats the beneficial use of EGCG (Epigallocatechin-3-gallate) in alleviating the oxidative stress induced during pulmonary fibrosis.
Tea is one of the most popular beverages worldwide. Modern medical research has provided a wide range of evidence that tea may be effective in various chronic disorders like cardiovascular diseases, various carcinomas, skin diseases, neurological disorders etc. as observed in various pre-clinical, clinical and epidemiological studies reviewed above.
Tea is an important dietary source of flavanols and flavonols. In the face of equivocal results from human studies, increasing knowledge about the bioactivity of tea-polyphenols should encourage further clinical investigations to uncover their actual contribution to promotion of health and prevention of chronic disease. Moreover, tea may be used as a biochemical modulator to enhance the therapeutic effectiveness of other drugs. While in totality the evidence from research on tea is very promising, more researches are needed to fully understand its contribution to human health.
Since, beneficial health effects of green tea are being increasingly proven; it would be advisable to encourage regular consumption of this widely available, tasty and inexpensive beverage as an interesting alternative to other drinks, like coffee or cola soft-drinks, which are rich in additives and/or CO2. We can conclude by saying that tea consumption (especially, green tea) is apparently an important means to maintain good health and it would be advisable to consider it for consumption on a regular basis.
The authors acknowledge the help and contributions of Dr. Pradip Kumar Mahanta, Ph.D, Exâ€“Scientist, Beverages Science & Technology Division (BeST), Unilever Research India, Bangaloreâ€“ 560 066, Karnataka (India).
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