Green Tea Extract

Ancient Health Secret of the Orient

The prefecture of Shizuoka, Japan has two claims to fame. First, it is the heart of this tea-drinking country's tea region. Not only do the inhabitants grow and process huge amounts of tea here, they also produce- and consume- large amounts of tea-containing products, including tea-flavored gum, candy, toothpaste, and even shampoo, not to mention drink multiple cups of tea every day.

Shizuoka is also becoming well known because of its extraordinarily low death rate from cancer, especially stomach cancer. When Japanese researchers looked more closely at the demographics of the region, they found that those towns with the highest tea consumption had the lowest levels of cancer.1

Coincidence? Not likely. Recent scientific studies are confirming at least 4000 years of folklore and medical practice in Asia regarding the incredible health benefits of green tea. Tea, and especially green tea, which is second only to water as the most common drink in the world, may also be the single most valuable substance you can take to protect your general health. The many health benefits of tea, all of which have been demonstrated in scientific studies, include:

Tea Polyphenols

The key fraction of the tea leaf (Camellia sinensis) that provides all these health benefits is a group of phytochemicals known as polyphenols. Long known as tea tannin because of their pungent taste, polyphenols constitute 15 to 30% of unfermented dried green tea and most of the soluble portion of tea. Thus, when you drink a cup of green tea, you're basically drinking a solution of tea polyphenols. In fresh, unfermented tea leaves, polyphenols exist as a series of chemicals called catechins, which include gallocatechin (GC), epigallocatechin (EGC),epicatechin(EC),epigallocatechin gallate (EGCg), and epicatechin gallate (ECg). As you can see in Figure 1, the largest component of fresh tea leaves is EGCg, which is fortunate, because it is also the most potent. Our focus so far has been on green tea, but we Westerners are most familiar with black tea, which has significantly fewer polyphenols, and thus appears to be generally less beneficial. Both black and green tea come from the same source, but the leaves that eventually become black tea are first broken up and exposed to air. This process promotes oxidation and deactivation of the valuable polyphenols. Green tea, on the other hand, is processed in a way that protects polyphenols by destroying the enzyme that oxidizes them. Consequently, green tea may contain as much as 90% more polyphenols than black tea. Before you run down to your local market to pick up some green tea, consider first that the amount of protection you get from green tea is directly proportional to how much of it you drink2 (Fig.2).

Sipping a cup at breakfast might help a little, but to reap the full protective rewards of green tea, you need to drink at least 5 to 10 cups a day. This level of tea consumption is not uncommon in Asia, but for most Americans it probably represents a significant shift.But take heart, drinking tea is not the only way to obtain its health benefits. Once it was discovered that tea catechins play such an important protective role, Japanese scientists went to work to isolate these key ingredients and translate them into a form that would (1) concentrate the nutrients in a smaller package and (2) put them in a vehicle that would be more accessible to non-tea drinkers. The result of these efforts is Life Enhancement's Green Tea Extract. Each Green Tea Extract capsule contains 40% polyphenols, including about 10% EGCg, the most biologically active and impressive of the polyphenols.

The clinical benefits of green tea are truly extraordinary. The following is a brief overview of some of the most important studies of the effects of tea on various disease states.

 

Cancer Protection

In addition to the observations of the people of Shizuoka, it is well known that Japanese men get less lung cancer than American men even though they smoke more cigarettes. It is thought that this difference may be due to their consumption of green tea. One study compared the frequency of a particular marker of lung cancer, the degradation of lymphocytes, in smokers and nonsmokers. Known as SCE (sister chromatid exchange in mitogen-stimulated peripheral lymphocytes), this marker was found to be significantly elevated in smokers who did not drink green tea whereas, in those who drank green tea, the SCE frequency was comparable to that of nonsmokers.3

When mice were exposed to the carcinogens in cigarette smoke, those fed green tea extract had 45% lower incidence of lung cancer than their control counterparts.4 Scores of similar studies have also demonstrated protection against cancers of the esophagus, stomach, skin, breast, pancreas, colon/rectum, and liver in vitro, in tea-drinking humans, and in animals fed green tea.5-10 Green tea has been found to be effective even against established skin cancers in mice.11, 12

"Japanese researchers... found that those towns with the highest tea consumption had the lowest levels of cancer."

Exactly how green tea fights cancer is currently under investigation in laboratories all over the world. Current theories are focusing on the antioxidant and antiproliferative effects of polyphenolic compounds. It is also thought that these polyphenols may inhibit carcinogenesis by blocking the endogenous formation of N-nitroso compounds, suppressing the activation of carcinogens, and trapping genotoxic agents.13 It may be possible that EGCg and other tea catechins block the interaction of tumor promoters with their receptors. This phenomenon has been described as having a kind of "sealing" effect, because these factors are neutralized by sealing them off from the receptors.14

 

Superior Antioxidant Activity

The antioxidant fraction of green tea extract has been shown to efficiently scavenge pro-oxidants such as hydrogen peroxide, the superoxide anion radical,15 and the ascorbyl radical.16 In a study comparing the antioxidant effects of green tea and black tea, green tea was found to be six times more potent. Curiously, this antioxidant activity may be attenuated by drinking tea with milk, possibly because the milk proteins neutralize the tea polyphenols.17 Green tea's antioxidant activity is particularly important for preventing lipid peroxidation, a crucial step in the formation of atherosclerotic plaque. Since lipid peroxidation is also a factor in the spoilage of oils and fatty constituents of many foods, anti- oxidants, including polyphenols and vitamin E, are often added to prevent rancidity. When two different concentrations of tea catechins were compared with two other powerful antioxidants, vitamin E and butylated hydroxyanisole (BHA), for their ability to protect fats and oils from oxidation, tea catechins were clearly superior (Fig. 3). The tea catechins were also able to suppress the photo-oxidation of certain oils, and showed marked synergistic effects with tocopherols (vitamin E), ascorbic acid (vitamin C) and some organic acids.

 

Fig. 3. Anioxidative activity of tea catechins, vitamin E, and BHA on salad oil.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Heart Disease Protection

Green Tea Extract provides protection against cardiovascular diseases by a variety of actions, including reducing platelet aggregation, lowering cholesterol, and decreasing blood pressure.

Antiplatelet activity. Platelets, which are cell fragments critical to the blood clotting process, have a tendency to clump together, or aggregate. When this occurs at the site of a wound forming a plug (or blood clot), it can be life-saving, but when it occurs inside blood vessels, it can lead to reduced blood flow, impaired oxygen delivery to certain tissue regions, and, ultimately, cellular death. Blood clots that prevent the normal flow of blood to the heart (heart attack/myocardial infarction) or brain (stroke) can be fatal.

Evidence suggests that Green Tea Extract possesses pronounced antiplatelet activity. EGCg, the most potent anti-clotting component of green tea, has antiplatelet activity comparable to that of aspirin. Unlike aspirin, though, EGCg does not irritate the stomach, and, also unlike aspirin, it blocks the platelet aggregation caused by Platelet Activating Factor (PAF), an action typically associated with extracts of Ginkgo biloba.18, 19

"Tea, expecially green tea... may also be the single most valuable substance you can take to protect your general health."

Cholesterol reducing activity. Feeding studies in animals have revealed a significant hypolipidemic action of Green Tea Extract. In one study, rats were fed a lard-enriched diet for 28 days; the diet of some of the animals was also supplemented with Green Tea Extract. Those rats fed the tea extract showed significant reductions in plasma total cholesterol, VLDL- and LDL- (the "bad") cholesterol, and relative increases in HDL (the "good") cholesterol.20, 21

In one experiment, rats were fed a high-fat, high-cholesterol diet. After 4 weeks, the total cholesterol concentration in the group that did not receive EGCg rose to more than twice the level of the control (normal diet) group. In particular, the LDL-cholesterol level increased by as much as 15-fold and the HDL-cholesterol level dropped by more than half. The addition of 0.5% EGCg to the diet suppressed the LDL-cholesterol increase to less than 8-fold and the decrease in HDL-cholesterol was completely inhibited. In those rats fed a diet containing 1.0% EGCg, this effect was even more pronounced. These results suggest that dietary hyperlipidemia can be controlled to a large degree simply by ingesting a green tea extract containing EGCg.

A similar beneficial effect seems to occur in humans. In one study of more than 2000 Japanese men aged 49-55, tea consumption (10 cups/day) was found to be significantly inversely associated with serum levels of total cholesterol and LDL-cholesterol, but not with HDL-cholesterol or triglycerides.22 Another study in a different population of more than 1300 Japanese males yielded a similar result.23

 

Antihypertensive Effect

In hypertension caused by high blood pressure, angiotensin I converting enzyme (ACE) converts angiotensin I to vasoconstrictive angiotensin II. By blocking this conversion, it is possible to prevent hypertension to a large degree. This is the mechanism that drugs known as ACE inhibitors exploit to treat this disease. But ACE-inhibiting drugs are not the only way to go.

It turns out that green tea polyphenols also have significant ACE-inhibiting ability. In one study, tea polyphenols were given to one group of genetically hypertensive rats beginning 1 week after weaning; a second group received a normal diet. After 16 weeks, the diets were switched. The blood pressure in the normal diet group already exceeded 200 mm Hg at age 10 weeks, compared with no clear rise in blood pressure in the tea polyphenol-treated group. When the diets of both groups were switched at 16 weeks, the blood pressure soon changed accordingly. In addition, the researchers found that the hypertensive rats on a normal diet were significantly more likely to die of a stroke.

 

Antibacterial and Antiviral Activity

Green tea has long been a folk remedy for treating diarrhea. Recent research has now revealed the reason. Tea catechins are powerful antibacterial and antiviral agents which makes them effective for treating everything from tooth decay to HIV. Studies have demonstrated that tea catechins can protect mice against infection by the bacteria that cause cholera and inhibit the activity of cholera toxin;24 inhibit the growth of Clostridium spp, which contributes to a variety of human diseases resulting in sudden death, toxicity, mutagenesis, carcinogenesis, and aging;25 and kill methicillin-resistant Staphylococcus aureus in the respiratory tract and also make these bacteria more susceptible to oxacillin.26

"When mice were exposed to the carcinogens in cigarette smoke, those fed green tea had 45% lower incidence of lung cancer than their control counterparts."

 

No less startling is the effect of green tea extract on viral infections. Japanese researchers have now demonstrated that EGCg and other tea polyphenols prevent the influenza virus from attaching itself to normal cells, thus blocking its infectivity. Even a small amount of EGCg seems to be capable of placing a significant obstacle in the way of the flu virus.27 Evidence also suggests activity against infections caused by rotavirus and enterovirus, which are common causes of diarrhea.28 Perhaps the best-documented antimicrobial effect of tea catechins is against the bacteria that cause tooth decay, Streptococcus mutans. In fact, green tea is probably better than fluoride for keeping teeth healthy.29 In one study, green tea was found to be far more effective than other forms of tea against S mutans (See Fig. 4). Another recent study found that EGCg completely inhibited the growth and cellular adherence of another important oral bacteria, Porphyromonas gingivalis.30 It has even been suggested that green tea be used as prophylactic treatment in root canal because of its broad spectrum of antibacterial and bactericidal activity.31

 

Using Green Tea Extract

Fig. 4. Antibacterial effect of tea against carcinogenic bacteria (S mutans)

So for those who want all of these health benefits but are daunted by the prospect of fitting 5 to 10 cups of tea into their daily routine, Green Tea Extract solves the problem by supplying the key tea polyphenols in a highly concentrated formulation.

Each 500-mg capsule of Green Tea Extract contains at least 40% highly purified polyphenols, including EGCg, equivalent to as much as 10 cups of green tea. Excessive caffeine is not a significant problem, because Green Tea Extract contains only a fraction of what is found in coffee. Considering the wide safety margin of Green Tea Extract and the fact that benefits have been documented at over 10 cups of tea per day, we recommend taking 1 to 5 capsules spread out throughout the day.

If you're concerned about protecting yourself from the bacteria that cause tooth decay, it is necessary to drink tea without milk. To do this, simply open a capsule of Green Tea Extract into a cup of hot water and let it steep, the way you would with any loose tea. Then drink up, being sure to swish the liquid around in your mouth so that it contacts all surfaces.

Extravagant claims are often associated with novel nutritional supplements and botanicals, but how many possess a history as rich as that of green tea, or have been exposed to as much scientific scrutiny? Perhaps the ancient Chinese medical book from the Tang Dynasty, Lost Property of Medical Herbs, was correct when it stated,

 

"Various medicines are the cure of different diseases, and tea is the cure to all diseases."

 

References

1.Oguni I, Nasu K, Kanaya S, Nomura T, Yamamoto S, Hara Y. A preliminary study on the protection against cancer risk by green tea drinking. Shizuoka, Japan: University of Shizuoka Hamamatsu College.
2. Sato Y, et al. Effects of green tea consumption on the reduction of brain-stroke history. J Exp Med. 1989;157:337-343.
3. Shim J, Kang M, Kim Y, Roh J, Roberts C, Lee I. Chemoprotective effect of green tea (Camellia sinensis) among cigarette smokers. Cancer Epidemiol Biomarkers Prev. 1995;4:387-391.
4. Brody J. Scientists seeking possible wonder drugs in tea. The New York Times. New York; March 14, 1991.
5. Hirose M, Hoshiya T, Akagi K, Takahashi S, Hara Y, Ito N. Effects of green tea catechins in a rat multi-organ carcinogenesis model. Carcinogenesis. 1993;14:1549-1553.
6. Khan S, Katiyar S, Agarwal R, Mukhtar H. Enhancement of antioxidant and phase II enzymes by oral feeding of green tea polyphenols in drinking water to SKH-1 hairless mice: possible role in cancer chemoprevention. Cancer Res. 1992;52:4050-4052.
7. Yamane T, Nakatani H, Kikuoka N, et al. Inhibitory effects and toxicity of green tea polyphenols for gastrointestinal carcinogenesis. Cancer. 1996;77 (8 Suppl):1662-1667.
8. Ji B, Chow W, McLaughlin A, et al. Green tea consumption and the risk of pancreatic and colorectal cancers. Int J Cancer. 1997;70:255-258.
9. Araki R, Inoue S, Osbourne M, Telang N. Chemoprevention of mammary neoplasia. In vitro effects of a green tea polyphenol. Ann NY Acad Sci. 1995;768:215-222.
10. Liao S, Umekita Y, Guo J, Kokontis J, Hiipakka R. Growth inhibition and regression of human prostate and breast tumors in athymic mice by tea epigallocatechin gallate. Cancer Lett. 1995;96:239-243.
11. Wang Z, Huang M, Ho C, et al. Inhibitory effect of green tea on the growth of established skin papillomas in mice. Cancer Res. 1992;52:6657-6665.
12. Mukhtar H, Katiyar S, Agarwal R. Green tea and skin anticarcinogenic effects. J Invest Dermatol. 1994;102:3-7.
13. Yang C, Wang Z. Tea and cancer. J Natl Cancer Inst. 1993;85:1038-1049.
14. Komori A, Yatsunami J, Okabe S, et al. Anticarcinogenic activity of green tea polyphenols. Jpn J Clin Oncol. 1993;23:186-190.
15. Ruch R. Prevention of cytotoxicity and inhibition of intercellular communication by antioxidant catechins isolated from Chinese green tea. Carcinogenesis. 1989;10:1003-1008.
16. Satoh K, Sakagami H. Ascorbyl radical scavenging activity of polyphenols. Anticancer Res. 1996;16:2885-2890.
17. Serafini M, Ghiselli A, Ferro-Luzzi A. In vivo antioxidant effect of green and black tea in man. Eur J Clin Nutr. 1996;50:28-32.
18. Segasaka-Mitane Y, Miwa M, Okada S. Platelet aggregation inhibitors in hot water extract of green tea. Chem Pharm Bull. (Tokyo). 1990;38:790-793.
19. Ali M, Afzal M, Gubler C, Burka J. A potent thromboxane formation inhibitor in green tea leaves. Prostaglandins Leukot Essent Fatty Acids. 1990;40:281-283.
20. Muramatsu K, Fukuyo M, Hara Y. Effect of green tea catechins on plasma cholesterol level in cholesterol-fed rats. J Nutr Sci Vitaminol (Tokyo). 1986;32:613-622.
21. Chisaka T, Matsuda H, Kubomura Y, Mochizuki M, Yamahara J, Fujimura H. The effect of crude drugs on experimental hypercholesterolemia: mode of action of
(-)epigallocatechin gallate in tea leaves. Chem Pharm Bull. (Tokyo). 1988;36:227-233.
22. Kono S, Shinchi K, Wakabayashi K, et al. Relation of green tea consumption to serum lipids and lipoproteins in Japanese men. J Epidemiol. 1996;6:128-133.
23. Kono S, Shinchi K, Ikeda N, Yanai F, Imanishi K. Green tea consumption and serum lipid profiles: a cross-sectional study in northern Kyushu, Japan. Prev Med. 1992;21:526-531.
24. Toda M, Okubo S, Ikigai H, et al. The protective activity of tea catechins against experimental infection by Vibrio cholerae O1. Microbiol Immunol. 1992;36:999-1001.
25. Ahn Y-J, Kawamura T, Kim M, Yamamoto T, Mitsuoka T. Tea polyphenols: selective growth inhibitors of Clostridium spp. Agric Biol Chem. 1991;55:1425-1426.
26. Takahashi O, Cai Z, Toda M, Hara Y, Shimamura T. Appearance of antibacterial activity of oxacillin against methicillin-resistant Staphylococcus aureus (MRSA) in the presence of catechin. Kansenshogaku Zasshi. 1995;69:1126-1134.
27. Nakayama M, Suzuki K, Toda M, Okubo S, Hara Y, Shimamura T. Inibition of the infectivity of influenza virus by tea polyphenols. Antiviral Res. 1993;21:289-299.
28. Mukoyama A, Ushijima H, Nishimura S, et al. Inhibition of rotavirus and enterovirus infections by tea extracts. Jpn J Med Sci Biol. 1991;44:181-186.
29. Sakanaka S, Kim M, Taniguchi M, Yamamoto T. Antibacterial substances in Japanese green tea extract against Streptococcus mutans, a cariogenic bacterium. Agric Biol Chem. 1989;53:2307-2311.
30. Sakanaka S, Aizawa M, Kim M, Yamamoto T. Inhibitory effects of green tea polyphenols on growth and cellular adherence of an oral bacterium, Porphyromonas gingivalis. Biosci Biotechnol Biochem. 1996;60:745-749.
31. Horiba N, Maekawa Y, Ito M, Matsumoto T, Nakamura H. A pilot study of Japanese green tea as a medicament: antibacterial and bactericidal effects. J Endodontics. 1991;17:122-124.

 

 

 

Green Tea Extract
Ancient Secret Unlocked 

Major studies have found a strong link between oral consumption of tea extracts (which contain polyphenols) and protection against experimentally induced: skin, stomach, esophagus, duodenum, pancreas, liver, breast and colon cancers.  Plus, green tea has been found to completely inhibit the growth and adherence of the oral bacteria, which cause gingivitis, a leading cause of periodontal disease and tooth loss.  And, green tea polyphenols have been found to be as rich in antioxidant power as BHT.

 

 

 

Green tea extract: The next big boost to weight loss

In addition to its potential cardioprotective action, green tea extract may serve as an aid to weight loss: in clinical trials it appears to raise metabolic rates and speed up fat oxidatin. Dulloo and colleagues at the University of Geneva, Switzerland, demonstrated that in addition to caffeine, green tea contains catechin polyphenols that raise thermogenesis (the rate at which calories are being burned) and overal energy expenditure. This metabolism-boosting effect seems to be independent of the supplemental caffeine the study's subjects consumed.

None of the ten healthy young male subjects were obese, ranging from lean to mildly overweight, and none of them was dieting during the study. A typical American non-weight-loss diet averaging 40% fat was prescribed during the course of research, and subjects were randomly assigned to each of three meals containing one of three treatments: green tea extract containing 50 mg of caffeine; 50 mg capsule of caffeine by itself; or a placebo capsule. On three separate occasions each subject spent 24 hours in a specially designed respiratory chamber in which thermogenesis and energy expenditure were carefully measured. When gauged by these relatively sedentary circumstances the subjects' thermogenesis showed a 4% increase, and overall energy expenditure increased by 4.5%.

Although millions of cultures throughout the world consume coffee and tea, only coffee's effect on fat metabolism--by virtue of its caffeine content--has been widely studied. But caffeine's increase of metabolic rates has only been noted at much higher doses than the 150 mg/daily of this study, which is barely the amount in one cup of brewed coffee. And since caffeine is known to increase heart rate, green tea appears to provide a safer alternative for obese patients who may have hypertension or other cardiovascular problems. Of particular interest in this sutdy is the fact that subjects who received only caffeine--not green tea--showed no change in their metabolic rates. Rather, the authors propose a synergistic interaction between caffeine and other bioactive ingredients in the green tea extract which helped to promote a higher rate of fat burning.

Dulloo A G 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: 1040-45.

 

 

 

 

 

Green Tea Extract

What is Green Tea?

When we first learned of the incredible new discoveries concerning green tea, we thought we were in for a long and tedious education on teas (we're all devoted coffee drinkers!). But we were pleasantly surprised (and our science writer quit coffee in favor of green tea!). Don't be daunted by the apparent myriad varieties of tea; by "tea" we mean the leaf of the plant, Camellia sinensis - other so-called "herbal teas" (a misnomer because Camellia sinensis is an herb) are meant to be any infusion other than that of Camellia sinensis. There are really only three categories of teas: green, oolong, and black. Each of these is the leaf of Camellia sinensis and differs only in duration of fermentation: "black" is fully fermented, "oolong" is partially fermented, and "green" is not fermented at all, only steamed. Types of tea such as Ceylon and Darjeeling refer to the region in which they are grown.

For What, and How is Green Tea Used?

What is great about green tea is its ability to ward off many types of cancer. Much of the initial evidence that green tea is anti-carcinogenic is based on epidemiological studies which show lower rates of many types of cancer among populations such as Japan and China that drink green tea as part of a daily cultural habit. Recently, however, controlled studies on green tea extract have yielded impressive results, identifying the polyphenol (-)-epigallocatechin gallate (EGCG) as the responsible component. EGCG is able to force certain cancer cells into a situation in which, incredible as it may seem, they must die or be killed; the cancer cells die in a sort of cellular suicide, a condition scientists call "apoptosis". Further evidence shows EGCG as having an inhibitory effect on the enzyme, urokinase, which is required for tumor formation, thus preventing the formation of tumors in the first place. Not only are the polyphenols in green tea protective against certain cancers, but they are also potent antioxidants. Green tea's antioxidants have been shown to be highly beneficial to the heart - they help prevent the oxidation of LDL cholesterol.

Things to know about green tea:

Tea polyphenols: prevention of cancer and optimizing health1,2,3

Hasan Mukhtar and Nihal Ahmad

1 From the Department of Dermatology, Case Western Reserve University, Cleveland.

2 Presented at the 17th Ross Research Conference on Medical Issues, held in San Diego, February 22每24, 1998.

3 Address reprint requests to H Mukhtar, Department of Dermatology, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106. E-mail: hxm4@po.cwru.edu.

 

ABSTRACT

The tea plant Camellia sinesis is cultivated in >30 countries. Epidemiologic observations and laboratory studies have indicated that polyphenolic compounds present in tea may reduce the risk of a variety of illnesses, including cancer and coronary heart disease. Most studies involved green tea, however; only a few evaluated black tea. Results from studies in rats, mice, and hamsters showed that tea consumption protects against lung, forestomach, esophagus, duodenum, pancreas, liver, breast, colon, and skin cancers induced by chemical carcinogens. Other studies showed the preventive effect of green tea consumption against atherosclerosis and coronary heart disease, high blood cholesterol concentrations, and high blood pressure. Because the epidemiologic studies and research findings in laboratory animals have shown the chemopreventive potential of tea polyphenols in cancer, the usefulness of tea polyphenols for humans should be evaluated in clinical trials. One such phase 1 clinical trial is currently under way at the MD Anderson Cancer Center in collaboration with Memorial Sloan-Kettering Cancer Center. This study will examine the safety and possible efficacy of consuming the equivalent of >=10 cups (>=2.4 L) of green tea per day. The usefulness of tea polyphenols may be extended by combining them with other consumer products such as food items and vitamin supplements. This "designer-item" approach may be useful for human populations, but it requires further study.

Key Words: Tea polyphenols • coronary heart disease • cancer • EGCG • (-)-epigallocatechin-3-gallate • antioxidant

 
INTRODUCTION

Significant progress has been made in understanding diseases that cause alarming mortality and morbidity in humans: their processes, possible prevention, and therapies. Cancer and coronary heart disease are the most important of these disorders. Because of research efforts over the past 30 y, it is now well appreciated that although the causes of the major diseases are diverse and countless, changes in dietary habits and lifestyles may reduce their risk in many cases. Research has indicated that many common foods have nonnutritive components, commonly known as chemopreventive agents, that may provide protection against a variety of illnesses, including cancer and coronary heart disease. One such class of agents is antioxidants. The predominant mechanism of protective action of antioxidants appears to be the destruction of free radicals.

The water extract of the dry leaves of the plant Camellia sinesis, an evergreen shrub of the Theaceae family, is a popular beverage commonly known as tea. A drink that contains many compounds, including a mixture of polyphenols, tea has been consumed by some human populations for many generations and, in some parts of the world, has been considered to have health-promoting potential (1). Extensive laboratory research and the epidemiologic findings of the past 20 y have shown that polyphenolic compounds present in tea may reduce the risk of a variety of illnesses.

 

CONSUMPTION, COMPOSITION, AND CHEMISTRY OF TEA

The tea plant C. sinensis is native to Southeast Asia but is currently cultivated in >30 countries around the world. Tea is consumed worldwide, although in greatly different amounts; it is generally accepted that, next to water, tea is the most consumed beverage in the world, with per capita consumption of {approx}120 mL/d (2). Of the total amount of tea produced and consumed in the world, 78% is black, 20% is green, and <2% is oolong tea. Black tea is consumed primarily in Western countries and in some Asian countries, whereas green tea is consumed primarily in China, Japan, India, and a few countries in North Africa and the Middle East. Oolong tea production and consumption are confined to southeastern China and Taiwan (2).

Green, black, and oolong teas undergo different manufacturing processes. To produce green tea, freshly harvested leaves are rapidly steamed or pan-fried to inactivate enzymes, thereby preventing fermentation and producing a dry, stable product. Epicatechins are the main compounds in green tea, accounting for its characteristic color and flavor.

For the production of black and oolong teas, the fresh leaves are allowed to wither until their moisture content is reduced to {approx}55% of the original leaf weight, which results in the concentration of polyphenols in the leaves. The withered leaves are then rolled and crushed, initiating fermentation of the polyphenols. During these processes, the catechins are converted to theaflavins and thearubigins. Oolong tea is prepared by firing the leaves shortly after rolling to terminate the oxidation and dry the leaves. Normal oolong tea is considered to be about half as fermented as black tea. The fermentation process results in oxidation of simple polyphenols to more complex condensed polyphenols to give black and oolong teas their characteristic colors and flavors.

The composition of the tea leaves depends on a variety of factors, including climate, season, horticultural practices, and the type and age of the plant. The chemical composition of green tea is similar to that of the leaf. Green tea contains polyphenolic compounds, which include flavanols, flavandiols, flavonoids, and phenolic acids and account for30% of the dry weight of green tea leaves. Most of the polyphenols in green tea are flavanols, commonly known as catechins; the major catechins in green tea are (-)-epicatechin, (-)-epicatechin-3-gallate, (-)-epigallocatechin, and (-)-epigallocatechin-3-gallate (EGCG). In black teas, the major polyphenols are theaflavin and thearubigin. The structures of the major polyphenolic compounds present in green and black tea are shown in Figure 1.

FIGURE 1. Major polyphenols present in green and black tea

 

TEA POLYPHENOLS AND THE RISK OF CANCER

 
Abundant experimental and epidemiologic evidence accumulated mainly in the past decade from several centers worldwide provides a convincing argument that polyphenolic antioxidants present in green and black tea can reduce cancer risk in a variety of animal tumor bioassay systems (2每4). Most of the studies showing the preventive effects of tea were conducted with green tea; only a few studies assessed the usefulness of black tea (2). These studies showed that the consumption of tea and its polyphenolic constituents affords protection against chemical carcinogen每 or ultraviolet radiation每induced skin cancer in the mouse model. Tea consumption also affords protection against cancers induced by chemical carcinogens that involve the lung, forestomach, esophagus, duodenum, pancreas, liver, breast, colon, and skin in mice, rats, and hamsters. We reviewed this area of research (2), and the bioavailability of the polyphenols from tea has been established by others (5). The relevance of the extensive laboratory information for human health can be assessed only through epidemiologic observations, however, especially in a population with high cancer risk.

Much of the cancer-preventive effects of green tea are mediated by EGCG , the major polyphenolic constituent of green tea (2). One cup (240 mL) of brewed green tea contains up to 200 mg EGCG. Many consumer products, including shampoos, creams, drinks, cosmetics, lollipops, and ice creams, have been supplemented with green tea extracts and are available in grocery stores and pharmacies.

The use of biochemical modulators in cancer chemotherapy has been studied extensively (6). The adverse effects of modulating drugs can be life threatening, and their use increases the patient's medication burden as well. Thus, the substances used in diet and beverages should be studied for their potential as biochemical modulators that could increase the efficacy of therapy. In this regard, Sadzuka et al (6) showed that the oral administration of green tea enhanced the tumor-inhibitory effects of doxorubicin on Ehrlich ascites carcinomas implanted in CDF1 and BDF1 mice. The study showed that green tea treatment increases the concentration of doxorubicin in tumor but not in normal tissue. If these observations can be verified in human populations, they may have relevance to cancer chemotherapy.

TEA POLYPHENOLS AND THE RISK OF CORONARY HEART DISEASE

Coronary heart disease is most prevalent in the Western world, probably as a result of the lifestyle in this part of the world, which includes a diet high in saturated fats and low physical activity, and the large proportion of the population who smoke cigarettes and have high blood pressure. A variety of epidemiologic studies showed the preventive effect of green tea consumption against atherosclerosis and coronary heart disease (see references 1 and 7 and the references therein). Tea consumption has also been shown to reduce the risk of high blood cholesterol concentrations and high blood pressure (8). In addition, studies in experimental animals showed the preventive effect of green tea against atherosclerosis (9).

EFFECTS OF TEA POLYPHENOLS AGAINST OTHER DISEASES

Many studies have shown that the consumption of tea or its polyphenols can afford protection against diseases other than cancer and coronary heart disease. A few of these studies are as follows: Weisburger (10) showed that tea is protective against stroke; Fujita (11) and Kao and P＊eng (12) reported that tea consumption lowers the risk of osteoporosis; Imai and Nakachi (13) reported protection against liver disease; Horiba et al (14), Terada et al (15), and Young et al (16) reported that tea consumption provides protection against bacterial infection; and Nakayama et al (17) and Tao (18) found that tea provides protection against viral infection.

ANTIINFLAMMATORY EFFECTS OF TEA

In several studies from our laboratory and elsewhere, the polyphenolic fraction from green tea was shown to protect against inflammation caused by certain chemicals, such as 12-O-tetradecanoylphorbol-13-acetate, a principal irritant in croton oil (2, 19, 20), or by ultraviolet radiation B (290每320 nm) (21). Green tea has also been shown to be effective against the immunosuppression caused by ultraviolet radiation B (2, 22). In addition, green tea polyphenols have shown protection against cytokines induced by tumors (23).

MECHANISMS OF BIOLOGICAL EFFECTS OF TEA

Because tea consumption has been shown to have protective effects against a variety of diseases, defining the mechanisms of the biological effects of tea is important. In addition, elucidation of mechanisms may provide additional opportunities to intervene at other targets. Initial mechanistic studies (reviewed in reference 2) regarding the cancer chemopreventive effects of green tea or its polyphenols largely focused on 1) protection against mutagenicity and genotoxicity, 2) inhibition of biochemical markers of tumor initiation, 3) inhibition of biochemical markers of tumor promotion, 4) effects on detoxification enzymes, 5) trapping of activated metabolites of carcinogens, and 6) antioxidant and free radical scavenging activity. Novel mechanistic work to define the anticarcinogenic effects of polyphenolic extracts from green tea and its constituents has been pursued; recent advances in this area are described in the following sections.

Green tea activates mitogen-activated protein kinases
The activation of mitogen-activated protein kinases by green tea polyphenols was shown to be a potential signaling pathway in the regulation of phase II enzyme gene expression mediated by an antioxidant-responsive element (24). In this study, green tea polyphenols induced chloramphenicol acetyltransferase (CAT) activity in human hepatoma HepG2 cells transfected with a plasmid construct containing an antioxidant-responsive element and a minimal glutathione S-transferase Ya promoter linked to the CAT reporter gene. This result indicates that green tea polyphenols stimulate the transcription of phase II detoxifying enzymes through the antioxidant-responsive element. In addition, green tea polyphenol treatment of HepG2 cells resulted in a significant activation of extracellular signal每regulated kinase 2 and c-Jun N-terminal kinase 1, which are members of the mitogen-activated protein kinase family. Green tea polyphenol treatment also increased messenger RNA amounts of the immediate-early genes c-jun and c-fos.

EGCG inhibits urokinase activity
A widely publicized study showed that the anticancer activity of EGCG in green tea might be due to inhibition of the enzyme urokinase (u-plasminogen activator), one of the most frequently expressed enzymes in human cancers (25). With the use of molecular modeling, the authors showed that EGCG binds to urokinase, blocking His 57 and Ser 195 of the urokinase catalytic triad and extending toward Arg 35 from a positively charged loop of urokinase. This computer-based calculation was verified by quantifying the inhibition of urokinase activity with a spectrophotometric amidolytic assay. The validity of this finding has been challenged, however (26).

Green tea induces apoptosis and cell cycle arrest
In recent years, apoptosis has become a challenging area of biomedical research. The life spans of both normal and cancer cells within living systems are thought to be significantly affected by the rate of apoptosis, a programmed type of cell death that differs from necrotic cell death and is regarded as a normal process of cell elimination (27). It follows that the chemopreventive agents that can modulate apoptosis and thereby affect the steady state cell population may be useful in the management and therapy of cancer. Many cancer-chemopreventive agents induce apoptosis and, conversely, several tumor promoters inhibit apoptosis (28每30). It is reasonable, therefore, to assume that chemopreventive agents that have proven effects in animal tumor bioassay systems or human epidemiologic studies on the one hand and that induce apoptosis of cancer cells on the other hand may have wider implications for the management of cancer. Only a few chemopreventive agents are known to cause apoptosis, however (31). We found that EGCG induced apoptosis and cell cycle arrest in human epidermoid carcinoma cells A431 (32). Importantly, we also found that the apoptotic response of EGCG was specific to cancer cells, because the induction of apoptosis was also observed in human carcinoma keratinocytes HaCaT, human prostate carcinoma cells DU145, and mouse lymphoma cells LY-R but not in normal human epidermal keratinocytes.

EGCG suppresses extracellular signals and cell proliferation through epidermal growth factor receptor binding
Liang et al (33) showed that EGCG could significantly inhibit DNA synthesis in A431 cells. In addition, EGCG inhibited the protein tyrosine kinase activities of epidermal growth factor (EGF) receptor, platelet-derived growth factor receptor, and fibroblast growth factor receptor but not of pp60v-src, protein kinase C, and protein kinase A. EGCG also inhibited the phosphorylation of EGF receptor by EGF and blocked the binding of EGF to its receptor. These findings suggest that EGCG might inhibit the process of tumor formation by blocking cellular signal transduction pathways.

EGCG blocks the induction of nitric oxide synthase by down-regulating transcription factor nuclear factor {kappa}B
Lin and Lin (34) assessed the effects of EGCG on nitric oxide production by murine peritoneal macrophages. Their results suggest that EGCG blocked early events of nitric oxide synthase induction by inhibiting the binding of transcription factor nuclear factor {kappa}B to the inducible nitric oxide synthase (iNOS) promoter, thereby inhibiting the induction of iNOS transcription.

EGCG and theaflavins inhibit tumor promoter-induced activator protein 1 activation and cell transformation
To examine antitumor promotion effects of EGCG and theaflavins at the molecular level, Dong et al (35) used a JB6 mouse epidermal cell line, a system that has been used extensively as an in vitro model for tumor promotion studies. EGCG and theaflavins inhibited EGF- or 12-O-tetradecanoyl-phorbol-13-acetate每induced cell transformation in a dose-dependent manner. EGCG and theaflavins also inhibited activator protein 1 (AP-1)-dependent transcriptional activity and DNA binding activity. Finally, this study showed that the inhibition of AP-1 activation occurs through the inhibition of a pathway dependent on c-Jun N-terminal kinase.

TEA AND CLINICAL TRIALS

Because epidemiologic studies and research findings in laboratory animals have shown the chemopreventive potential of tea polyphenols in cancer, the usefulness of these polyphenols for humans should be evaluated in clinical trials. The first such trial is being conducted by the MD Anderson Cancer Center in collaboration with the Memorial Sloan-Kettering Cancer Center; MD Anderson has obtained an Investigational New Drug application permit from the US Food and Drug Administration to begin phase 1 clinical trials. To examine the safety and possible efficacy of consuming the equivalent of >=10 cups (>=2.4 L) of green tea/d, 30 cancer patients with advanced solid tumors will be given daily capsules of formulated powdered green tea for >=6 mo (if the treatment appears beneficial).

CONCLUSION AND FUTURE DIRECTIONS

Dietary habits influence the risk of developing a variety of diseases, especially cancer and heart disease. The use of dietary substances is receiving increasing attention as a practical approach for reducing the risk of developing these diseases. Epidemiologic observations and laboratory studies have indicated that tea consumption may have beneficial effects in reducing certain types of cancer in some populations. Although a considerable body of information provides evidence supporting the preventive potential of tea against cancer, a proper understanding of the mechanisms by which tea polyphenols reduce the risk of diseases is necessary to devise strategies for better health. Black tea is the major form of tea consumed, but its chemistry, biological activities, and chemopreventive properties, especially of the polyphenols that are present, are not well defined.

Because information on the bioavailability of tea polyphenols after tea consumption is limited in humans, studies on absorption, distribution, and metabolism of green and black tea polyphenols in animals and humans are needed. After careful evaluation of the available data and additional studies, specific recommendations may be made for consumption of tea by humans. The usefulness of tea polyphenols may be extended by combining them with other consumer products, such as food items and vitamin supplements. This "designer-item" approach may be useful for the human population.

 
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