Much attention, in both the popular press and scientific literature, has focused on the potential of green tea to lower cancer risk. Many epidemiologic studies have suggested that green tea is a cancer chemopreventive agent, but experts agree the studies are inconclusive.
Tea consumption is second only to water consumption in the world, and tea is grown in about 30 countries. Green teas suggested benefit as a preventive agent, its low toxicity, low cost, and natural abundance make it an attractive substance to investigate as a dietary supplement.
Green tea consumption has been associated in epidemiologic studies with decreased risk of many cancers, including those of the prostate, colon, and esophagus. Other studies, however, have suggested either no benefit or in some instances, such as bladder cancer, increased risk.
In a variety of cell culture and animal model systems, green tea has shown sufficient anticancer effects to warrant studies ranging from its mechanism of action in vitro to phase III randomized clinical trials.
Tea Polyphenols
In one in vivo experiment, mice that were fed green tea and exposed to carcinogens prevalent in cigarette smoke developed 45% fewer lung tumors than non-tea-drinking controls. Polyphenolic antioxidants, or catechins, have been identified as the active ingredients in green tea that are responsible for such anticarcinogenic effects.
The antioxidant activity of these compounds is 25 and 100 times more potent than vitamins E and C, respectively. The most potent of the catechins in green tea is epigallocatechin gallate (EGCG). EGCG is the most powerful antioxidant present in any plant-derived material, said Hasan Mukhtar, Ph.D., professor and director of research at Case Western Reserve University, Cleveland.
Green tea contains greater amounts of polyphenols (30% to 40% of dry weight) than oolong or black teas because it is processed differently, but other teas do have potential health benefits that are under investigation.
At a recent American Chemical Society meeting, Roderick Dashwood, Ph.D., principal investigator at Oregon State Universitys Linus Pauling Institute, Corvallis, Ore., reported that white tea, which has higher levels of polyphenols, may be even more beneficial than green tea for cancer prevention. Dashwood is exploring the inhibitory effects and potential mechanisms of action of white tea in vivo, particularly in colorectal cancer.
In parallel with these studies, the Linus Pauling Institute is planning a small clinical trial that will examine the relationship between white tea consumption and colon cancer risk.
Mechanism of Action
The polyphenols present in green tea, particularly EGCG, appear to affect a number of molecular processes, including induction of tumor cell apoptosis and inhibition of tumor growth, invasion, and angiogenesis, and research is under way to define the precise molecular processes affected.
Yihai Cao, M.D., Ph.D., associate professor at the Karolinska Institute, Stockholm, has found that physiological concentrations of EGCG prevent the proliferation of endothelial cells, thereby inhibiting angiogenesis. Furthermore, EGCG inhibited angiogenesis mediated by the potent angiogenic factor vascular endothelial growth factor (VEGF).
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Although tea and its constituents appear to affect many biologic processes, such effects are observed only under experimental conditions, noted Chung Yang, Ph.D., professor of chemical biology at Rutgers University, Camden, N.J. "The concentrations used in many studies are unreasonably high," said Yang, in comparison to levels measured in human blood and serum after oral consumption.
Yang is studying the metabolism of tea polyphenols to better understand how they are absorbed and metabolized. These studies will help determine the pharmacodynamic and pharmacokinetic properties of green tea following consumption.
Current and Future Studies
In addition to molecular-based studies, the anti-cancer effects of green tea are under evaluation in clinical trials.
EGCG is capable of blocking UVB-induced skin cancer in mice. At the University of Arizonas Arizona Cancer Center, Tuscon, researchers are conducting a human clinical trial to analyze the effect of oral and topical formulations of a green tea mixture containing EGCG on skin cancer prevention. The phase I trial is expected to be completed in summer 2000. Since EGCG cannot be synthesized, David Alberts, M.D., associate dean of research at the University of Arizona College of Medicine, said he expects that chemists will soon initiate programs to develop an EGCG analog that is more potent but less expensive.
Other human trials involving green tea include an oral cancer prevention trial in China and at the University of Texas M. D. Anderson Cancer Center, Houston, and a phase III randomized study of the effect of green tea on prostate-specific antigen levels in prostate cancer patients at Memorial Sloan-Kettering Cancer Center, New York.
A phase II randomized trial is also set to begin soon that will study the effectiveness and toxicity of green tea extract in patients with androgen-independent metastatic prostate cancer.
Several researchers have emphasized the importance of testing green tea in randomized clinical trials. "This is not a one-size-fits-all approach," Mukhtar said. "What is good for cancer in one population may not be good for another. It is naive to believe that all prostate cancers will be inhibited by green tea."
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