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tea and cancer prevention 
programmed death of cancer cells 
modulation of cancer chemotherapy 
tea and health diseases 
tea and stroke 
tea and inflammation and arthritis

Tea is an inexpensive, and next to water, the most widely-consumed beverage worldwide. Modern science, especially of the last fifteen years, is beginning to confirm that tea has health-promoting potential, a concept advocated by Asian traditional for centuries. In fact, the medicinal value of tea has been recognized for a long time in as much as tea was used as an elixir by ancient Chinese. When tea was introduced to Europe, people of Holland considered it a divine herb, a panacea.

Tea is derived from the plant Camellia sinensis, an evergreen shrub of the theaceae family. The tea plant Camelia sinensis was originated in Southeast Asia and is presently cultivated in over 30 countries around the world. Of the total tea produced and consumed in the world, 78% is black tea, 2% is oolong tea. Black tea is mainly consumed in western countries and some Asian countries including India. Green tea is consumed mainly in Chine, Japan, India, and a few countries in North Africa and Middle East. Oolong tea production and consumption is confined to southeastern China and Taiwan. Both green and black teas contain main polyphenolic antiooxidants. Polyphenols, in chemical term, are members of the flavonoid family. They are catechins made of several ring-like structures.

Each of these structures has chemicals attached to it called phenol groups, hence the name polyphenols (poly means "many"). Antioxidants are the chemicals endowed with the ability to counteract the adverse effects of oxidants by scavenging them or by interfering with their production. The oxidant species are constantly produced within the living system and are responsible for many diseases. By trapping these oxidant radicals, the antioxidants reduce their effective bio-availability. This represents a highly efficient built-in preventive machinery within a living cell. The water-extract of the dry tea leaves, as is consumed by humans, contains many compounds including a mixture of polyphenols. Green tea contains flavanols, flavandiols, flavonoids, and phenolic acids, which are antioxidant in nature. These compounds account for up to 30% of the dry weight of green tea leaves. Most of the polyphenols present in green tea are flavanols, commonly known as catechins.

The major catechins present in green tea are:
- epicatechin (EC)
- epicatechin-3-gallate (ECG)
- epigallocatechin (EGC), and
- epigallocatechin-3-gallate (EGCG)

The major polyphenolic antioxidants present in black tea are i) theaflavins such as theaflavin-3-gallate, theaflavin-3'-gallae, theaflavin-3,3'-digallate, ii) thearubigens and their derivatives such as theafulvins and theacitrins, and iii) tannins such as pentagalloylglucose and camelliatanin A. In black tea, in addition to its own specific poly phenolic antioxidants, some green tea-specific polyphenolic antioxidnts are also present. Their quantity, however, depends on the fermentation process employed during the manufacture.

Extensive laboratory research and he epidemiological findings have revealed that the polyphenolic antioxidant of tea are far superior than the antioxidants in any other edible produce known to mankind. For example, it has been shown that the trolox equivalent antioxidant capacity of green tea (1000 ppm) and black tea (1000 ppm) is between 3.5-3.8 and of vitamin C and vitamin E is 1.0. Because most beneficial or harmful physiological responses are regulated by the balance between prooxidants and antioxidants, it is no wonder that tea which is rich in antioxidants possesses numerous health-promoting effects. Indeed, the experimental findings indicate that it can protect against the risk of many diseases. The focus of this presentation is consumption of tea in the prevention of cancer, heart disease, stroke and arthritis.

Tea and Cancer Prevention

Abundant experimental and epidemiological data accumulated mainly in the last decade, from several laboratories worldwide, provided convincing evidence that polyphenolic antioxidants present in green as well as in black tea are capable of affording protection against cancer risk in a variety of animal tumor bioassay systems. Initial studies in this area of research reported from our laboratory showed that the consumption of tea and its polyphenolic fraction afforded protection against chemical carcinogen  - or ultraviolet radiation - induced skin cancer in mouse model. This work laid the foundation for many subsequent studies from several laboratories around the world.

Collectively, these studies show that tea consumption affords protection against chemical carcinogen-induced lung, forestomach, esophagus, duodenum, pancreas, liver, breast and colon carcinogensis in mice, rats and hamsters. These laboratory findings suggests that tea consumption by humans may result in prevention of some cancer types.

Recent studies from our laboratory have shown that green as well as black tea may also prevent prostate cancer. These laboratory findings may explain geographical difference in prostate cancer incidence. It is important to note that the Japanese and Chinese populations which traditionally consume a diet having low fat and several cups of tea, have one of the lowest rates of prostate cancer in the World. Furthermore, the incidence of prostate cancer in India, a population that consumes tea regularly is lower than the Western countries.

Our recent study conducted in mice has demonstrated that intraperitoneal injections of EGCG, known to present in green as well as black ea, results in a significant reduction in grown of human prostate cancer cells in nude mice. In this study, prostate tumors were developed by implanting human prostate cancer cells via injections on the backs of athymic nude mice. It was found that daily injections of 1 mg of EGCG resulted in a significant reduction in prostate tumor growth as well as in the levels of prostate-specific antigen, which is regarded as a gold standard for prostate cancer diagnosis and to assess prostate cancer body burden in humans.

Tea Antioxidants and a Programmed Death of Cancer Cells

A study from a laboratory has shown that tea antioxidant EGCG results in an induction of a programmed cell death technically known as 'apoptosis' of many human cancer cells including human prostate cancer cells.

Interestingly, under similar conditions, EGCG  did not kill the normal cells. This observation was subsequently varified by many laboratories worldwide. In subsequent studies, black tea antioxidants were also found to cause apoptotic death of cancer cells. These studis suggest that tea polyphenols may have advantage in killing cancer cells without harming normal sells.

Modulation of Cancer Chemotherapy by Tea

A recent study has shown that green tea can also modulate cancer-chemotherapeutic drugs in such a way that their efficacy is increased. In this study, the oral administration of green tea was found to enhance the tumor-inhibitory effects of doxorubicin, on Ehrlich ascites carcinomas implanted in mice.

Green tea treatment resulted in an increased availability of doxorubicin in tumors, but not in normal tissue. In another study, theanine, an amino acid present both in black and green tea, was found to enhance the inhibition of liver metastasis induced by doxorubicin.  Furthermore, in vitro experiments indicated that theanine increased the intracellular concentration of doxorubicin in cancer cells. If verified in the human population, these observations may have relevance to cancer chemotherapy.

Tea and Health Diseases

Tea consumption may lead to the prevention of heart disease. Tea has been shown to strengthen blood vessels and to decrease the cholesterol level in the bloodstream. Epidemiological studies has shown the preventive effect of green tea consumption against atherosclerosis and coronary heart disease. In some studies, tea consumption has been shown to afford protection against high cholesterol levels and high blood pressure. More research in this area is required. Studies have also shown the preventive effect of green tea against atherosclerosis in experimental animals. In a Japanese study, the atherogenic index that is a measure for the risk of atherosclerosis was found to be significantly lower in rats fed with a high-cholesterol diet supplemented with black tea extract than in the ones not given the extract. In this study, black tea was also found to inhibit the proliferation of smooth muscle cells involved in the development and progression of atherosclerosis. This study suggested that black tea possesses an anti-atherosclerotic action.

In hamster model, both black as well as green tea has been shown to decrease the risk for heart disease. In this study, the hamsters were fed a normal or high cholesterol diet and green or black tea. Tea consumption was found to result in a significant improvement in the plasma lipid profile and a decrease in the oxidation of lipids. This study suggests that both black and green teas improve the risk factors for heart disease.

Tea and Stroke

Some studies have shown that tea consumption ma reduce the risk of stroke. In a study, the effect of EGCG on the life span and hypertensive lesions in the stroke-prone spontaneously hypertensive rat (SHRSP) was compared with that of persimmon tannin. In this study, it was found that a long-term administration of either 0.5% EGCG or 0.5% persimmon tannin to SHRSP inhibited the incidence of stroke and prolonged the life span. These results suggested that green tea may prevent incidence of stroke. Similarly, in another study among 5910 non-drinking and non-smoking women, it was found that the incidence of stroke and cerebral hemorrhage during a 4-year follow-up of the study population was twice or more higher in those who took less tea 9less than 5 cups a day) than in those who took more tea (greater than or equal to 5 cups daily). These studies show a possible connection between of tea-drinking and the prevention of stroke.

I an epidemiological study, where a cohort of 552 men aged 50 to 69 years was examined in 1970 and followed up for 15 years, it was found that the habitual intake of black tea may protect humans against stroke.

Tea and Inflammation and Arthritis

In several studies from my laboratory and elsewhere, the polyphenolic fraction prepared from both green and black teas have been shown to prevent against inflammation caused by chemicals and ultraviolet radiation. In a recent landmark study, we showed that mice drinking green tea developed lower incidence and milder form of collagen-induced arthritis, which is similar to that of rheumatoid arthritis in humans. Importantly, the biological markers of arthritis progression were negatively regulated in the animals consuming green tea. This study concluded that the antioxidants present in green tea might retard the onset and incidence of inflammatory diseases including arthritis. Data from a study recently completed in my laboratory examining simultaneously the effects of black and green tea consumption on arthritis incidence and disease severity in mice will be presented for the first time in this meeting.

 

Source: Abstract of talk at
International Millennium Tea Convention
New Delhi, India
by Hasan Kukhtar, PhD
Professor and research Director
Department of Dermatology
Case Western Reserve University
Cleveland, OH-44106, USA

 

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