Tea and Cancer
Roderick H. Dashwood, Ph.D.
According to legend, tea was discovered in the year 2737 BC by the Chinese emperor Sheng Nung. The medical uses of this beverage were first reported by Chinese scholars in a text written sometime in the first few centuries. Tea was first introduced into Europe at the start of the sixteenth century and reached England and North America by the mid-1600s, then very rapidly became an important commercial product throughout the world. At one time, tea was actually more valuable than gold! In 1996, annual world tea production was immense, about 2,600,000 metric tons.
Tea is the beverage obtained from steeping the leaves of the plant Camellia sinensis in hot water. Green tea is produced by hand-picking fresh leaves (or to be more accurate, two leaves and a bud), which are subsequently subjected to manufacturing processes called "withering" and "firing" After withering and before firing tea can be rolled (oolong) or rolled and fermented (black). Tea that has only been "withered" and "fired" is called green tea.
The distinctive colors, aromas and flavors of each tea result from chemical changes in the leaf caused by the various processing steps. The leaf contains many chemicals (e.g. flavonoids and methylxanthines) that provide a rich and diverse array of biological activity. Much has been written about the physiological and pharmacological properties of tea or its constituents, but attention has focused most recently on the potential health benefits of tea against chronic diseases, particularly cancer. Does evidence from human and animal research support this proposed benefit?
Diet and cancer
Cancer is not a single disease, but rather a number of diseases characterized by uncontrolled growth and spread of abnormal cells in the body that are caused by both internal and external factors. Of the external factors, the two major contributors to cancer deaths are tobacco use and poor diet. Indeed, it has been estimated that fully one third of all cancers are related to tobacco use and one third to poor diet. We usually think of diet as the food we eat, but it is important also to consider the fluids we drink and their possible contribution to health. While the importance of drinking plenty of fresh, clean water is generally well known, it is not widely recognized that a glass of grapefruit, orange or other fruit juice can be counted as one serving when following the American Cancer Society dietary guidelines of "five or more servings of fresh fruit and vegetables per day" to help prevent cancer (American Cancer Society, website: http://www.cancer.org). Is it possible that, like fruit and vegetable juices, tea might provide substances that help prevent cancer? An examination of human and animal studies may help answer this question.
Ironically, the earliest studies on tea and cancer hinted at the possibility that tea might actually cause cancer. Initial evidence suggested that some populations drinking large quantities of tea had higher rates of esophageal cancer, but upon careful examination it was found that the high rates of this particular cancer were due to the temperature at which the tea was consumed rather than the tea itself. For example, in some parts of northern China it is customary to drink very hot tea, and this was associated with a 2- to 3-fold increase in risk for esophageal cancer. In the U.S., U.K., Australia and many other countries, it is customary to drink either iced tea or tea with lemon or milk, and thus its temperature is lower.
Black tea accounts for over 90% of the tea consumed world-wide. At present, there is no clear evidence that populations drinking large amounts of black tea have correspondingly lower cancer rates. Indeed, a recent scientific review article by Dr. William Blot and colleagues of the International Epidemiology Institute in Rockville, Maryland, showed very clearly that populations with the highest per-capita black tea consumption (New Zealand, U.K. and Ireland) had about the same cancer mortality rates as countries with the lowest tea consumption (Italy, Belgium, Austria and France). Is it possible that black tea protects against some cancers and not others, so that an analysis of "total cancers" doesn’t provide enough insight? To answer this question, Blot and colleagues looked at the published data for the effect of black tea on cancers of the esophagus, stomach, large intestine (colon/rectum), pancreas, lung, breast and bladder. They concluded that "several investigations point to the possibility of somewhat lowered risks of digestive tract cancers...", but consistent patterns have yet to emerge because the "data on amount and duration of black tea intake are often limited".
Is the same true of green tea? Green tea is consumed widely in Japan, China and Korea, as well as in some states of the U.S. (Hawaii and California), and the media have given particular attention in recent years to green tea for its anti-cancer role. Dr. C.S. Yang and colleagues at Rutgers University reviewed the research on tea consumption and human cancer, including many of the studies on green tea, and found that protection against cancer was observed in some investigations. In Kyushu, Japan, individuals who consumed green tea frequently (10 cups per day) had a lower tendency to develop stomach cancer, and there was a general trend of "more cups equals more protection".
Recently, scientists at the Chinese Academy of Preventive Medicine showed that a mixed-tea product containing green tea and tea pigments could help prevent or partially regress pre-cancerous lesions in the mouth (so-called "oral mucosal leukoplakia") when applied directly to the lesion. In a study of 2,454 people in Shanghai, China, frequent green tea consumption lowered the incidence of esophageal cancer in women, but no effect was seen in men unless smokers and those who regularly consumed alcoholic beverages were excluded. In China, women do not usually smoke or consume alcohol. What, then, does this tell us about the relative importance of tea versus other factors, such as smoking and alcohol, as means for lowering cancer incidence and mortality in a population? Does tea reduce significantly the cancer rates in populations that drink lots of this beverage? At present, the simple answer seems to be "no, not markedly or consistently". Certain risk factors, such as smoking, poor diet, alcohol and obesity, appear to outweigh or obscure the benefits from drinking tea. While drinking tea cannot compensate for bad habits, such as smoking and eating a poor diet, carefully designed human studies that exclude confounding factors might give a better understanding of the real benefits of tea. This belief is based on the large body of evidence that has accumulated on the protective effects of tea from in vitro and animal studies.
One major advantage of in vitro and animal studies is that they allow one to study, under carefully controlled and defined conditions, specific protective effects of tea without other confounding influences. For example, when confounding factors like poor diet and smoking are avoided and animals are given nutritionally balanced food, cancer protection by tea clearly can be observed. Skin cancer has been the most extensive focus for tea research because the tumors are readily detectable, and protective effects of tea treatment can be quickly ascertained by palpation (feeling the tumor with fingers and measuring size and shape with calipers). Exposure to ultraviolet light or to certain chemical carcinogens produces skin tumors in animals. These have been inhibited very effectively by different teas (including decaffeinated varieties) or their active constituents, the polyphenols, which are phytochemicals widely distributed in fruits and vegetables that possess antioxidant properties. Other studies showed that green tea and black tea inhibited lung, forestomach and liver tumor formation in mice, and esophageal tumor formation in rats.
In our studies, green tea and black tea inhibited the formation of pre-cancerous lesions, so-called "aberrant crypt foci" (ACF, see photo at left) induced in the large intestine of the rat by mutagens from cooked meat (see the article by Rod Dashwood in the Fall/Winter 1998 LPI Newsletter). Using ACF as a biomarker, we treated rats with a mutagen from cooked meat (2-amino-3-methylimidazo[4,5-f]quinoline, or "IQ"), or with IQ plus green or black tea. As shown in the figure below, 71% of the animals given only the carcinogen developed ACF, whereas only 20% of the rats given green tea and 33% of the rats given black tea had ACF following treatment with the carcinogen. Among those animals bearing ACF, an average of 2.4 ACF per colon were found in the group given only the carcinogen, compared with 1.0 ACF and 1.6 ACF per colon in rats given the carcinogen plus green tea or black tea, respectively. Thus, both teas reduced the incidence and frequency of pre-cancerous lesions in the colon.
Mechanisms of inhibition
Tea is a complex mixture of chemicals. To understand exactly how tea might prevent cancer, it has been separated into various fractions, and these fractions have subsequently been examined for inhibitory activity using different tests. Green tea contains high levels of polyphenols called catechins. As green tea is processed into oolong and then black teas, these catechins link together (oxidize) to form other, larger molecules called theaflavins, thearubigins and theafulvins. Generally, the catechins in green tea have been reported to have the highest antioxidant activity. Indeed, in test tube experiments, tea catechins are more effective antioxidants than either vitamin C or vitamin E. Might this be true in vivo? Research in Saitama, Japan, showed wide distribution of the major tea catechin, epigallocatechin gallate (or EGCG), in mouse tissue following oral administration, which indicates that the compound is "bioavailable". Additionally, Dr. C.S. Yang recently established that, after "swilling" tea catechins in the mouth, EGCG and other tea catechins were readily detected in saliva and later passed in the urine, even though people did not swallow any tea during the experiment. In other words, the lining of the mouth is a good place for absorption of tea polyphenols into the body.
EGCG, an excellent antioxidant, is the most actively studied of the tea polyphenols, but other tea constituents might be important against cancer, either singly or in combination. In fact, synergistic effects of EGCG with other tea catechins have been observed -- studies using cells in culture established that tea constituents could combine for greater activity and work with other known cancer inhibitors for greater protection. Recently, scientists at the American Health Foundation in Valhalla, New York, showed that black tea inhibited the formation of lung tumors in rats given carcinogens from tobacco known as "tobacco-specific nitrosamines". Surprisingly, caffeine itself remarkably reduced the incidence of lung tumors!
Since caffeine is not considered a strong antioxidant (but may have some antioxidant function), other properties might be important in the anti-cancer effect of tea. Caffeine, when consumed at the levels that occur in tea and coffee, can alter the amounts or activities of some enzymes in the body which metabolize carcinogens and other foreign compounds. For example, we have shown that green tea and black tea can help prevent certain liver enzymes from converting heterocyclic amine mutagens into molecules that can damage DNA. Caffeine also increases the activity of detoxification enzymes under some circumstances. However, caffeine also has widely-known pharmacological properties that render it less suitable than more benign dietary compounds.
In many experimental animal and human studies, a test compound is usually administered at doses far above the levels typically encountered in the human diet. Perhaps the most encouraging finding from animal experiments is that cancer inhibition by tea occurs at concentrations that are dietarily relevant. Typically, tea is made at a concentration of about 2%; that is, 2 grams (about 1/10 oz) of tea leaves are brewed in 100 milliliters (about 3 1/2 oz) of water--boiling for black tea (followed by 3-5 minutes of brewing), below boiling for green tea. This concentration of tea is very effective in many animal studies, and since people find even higher concentrations of tea quite palatable, future human trials should examine tea concentration as a variable. Other important issues to consider are brewing time, type of tea, frequency of tea consumption and timing of tea consumption relative to food intake. When these are incorporated into more carefully designed human clinical trials in the future, we might well expect to find a measure of modest benefit from drinking tea in the fight against cancer, and, possibly, other chronic diseases like heart disease and stroke.
For more information on tea, see the Linus Pauling Institute's Micronutrient Information Center.
Last updated May, 1999
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