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ISIS Press Release 24/01/07

Green Tea Against Cancers

More evidence emerges on green tea and cancer prevention though it is hard to pin down the molecules involved Dr. Mae-Wan Ho

A fully referenced version of this article is posted on ISIS members’ website. Details here

FDA rejects claims that green tea may reduce the risk of cancer but scientists disagree

In June 2005, the US Food and Drug Administration (FDA) issued its rejection of qualified health claims that green tea may reduce the risk of certain types of cancer [1]. In particular it singled out breast and prostate cancer, considering it “highly unlikely” that green tea reduces the risk of either.

Many disagree [2] ( Green Tea, The Elixir of Life? , this series), among them, the American Institute for Cancer Research (AICR) [3]. At its annual conference in July 2005, there were six separate presentations on the benefits of green tea, and no tea companies were involved in the research.

In a study using cancer cells from mice, Thomas Gasiewicz, a professor of environmental medicine at the University of Rochester in New York, found that epigallocatechin-3-gallate (EGCG) molecules, the main flavonoid from green tea, bind to and inhibit the action of the heat shock protein hsp90, which is found disproportionately in cancer cells.

“Based on the animal studies, it's hard for me to believe that, at least at some dose, (EGCG) would not have a protective effect in the human population,” Gasiewicz said to reporters.

An AICR fact sheet said the benefits of green tea are under-utilized in the US population. A telephone survey conducted by the organisation found only 15 percent of Americans said they drink green tea everyday, compared to 62 percent who drink soft drinks and 61 percent who drink coffee every day.

In contrast, average per-capita consumption of green tea in Japan and China is three to four ounce cups a day.

Jeffrey Prince, vice-president for education and communications of the AICR said: “People who drink cola or coffee on a regular basis might consider substituting green tea for one of those servings.”

Further new research results have appeared in 2006 that tip the balance in favour of drinking green tea to prevent cancer or delay the onset of cancer (see below). There are many animal studies that corroborate the findings in human studies, but according to the FDA, they can only form the ‘background', and do not offer definitive proof, which require randomised, controlled intervention studies [4]. If that is the case, further animal studies are hard to justify, especially those involving creating cancers or illnesses in animals to serve as dubious models of human diseases.

As part of a Program Project sponsored by the US National Institutes of Health, a phase II chemoprevention trial is currently conducted on heavy smokers by a consortium of cancer centres and universities in Canada and the United States, using a standardized decaffeinated preparation – Polyphenon E [5]. This trial will recruit former smokers between the age of 45 and 74 years of age. Individuals with precancerous lesions are identified with image analysis of sputum cells. The study is designed to be double-blind, randomised and placebo-controlled. This will be the first clinical trial of its kind, meanwhile….

Breast cancer in southeast China

Women drinking green tea can cut the risk of breast cancer by 40 percent. This is the result of the latest study from southeast China [6].

Although a number of reports around the world have linked the consumption of green tea with reduced risk of breast cancer [2], there were also reports that found no effect. A joint study, carried out by researchers at the University of Western Australia, Perth, Australia and Zhejiang University, Hanzhou, China, has now added to the evidence that green tea drinking does reduce risks of breast cancer.

The study, conducted in Zhejiang Province, southeast China, between 2004 and 2005, involved 1 009 female patients aged 20-87 with confirmed breast cancer and 1 009 age-matched healthy women controls randomly recruited from breast disease clinics.

Information on tea consumption, diet, and lifestyle were collected by face-to-face interview.

The results showed that compared with non-tea drinkers, green tea drinkers tended to reside in urban areas, have better education and higher consumption of coffee, alcohol, soy, vegetables and fruits.

After adjusting for established and potential confounding factors, green tea consumption was associated with a reduced risk of breast cancer. The risks relative to non-tea drinkers were 0.87 for consumption of 1-249 g dried green tea leaves per annum, 0.68 for 250-299 g per annum, 0.59 for 500-749g per annum and 0.61 for 750 g or more per annum; with a statistically significant trend at p<0.001. Similar dose-response relationships were also found for the duration of drinking green tea, the number of cups consumed and new batches prepared per day.

The conclusion is that regular consumption of green tea can protect against breast cancer.

The authors point out that most studies yielding null results were conducted in western populations that consumed exclusively black tea. While two case-control studies conducted on Asian Americans and Chinese women in Singapore found that green tea reduced the risk of breast cancer, three cohort studies from Japan report no association between green tea and breast cancer risk, possibly because it was hard to find Japanese people not drinking any green tea at all. Failure to adjust for confounding factors such as education, diet and lifestyle could also contribute to null findings, while contaminants such as aluminium and fluoride from industrial pollution may also result in negative findings [7, 8] ( Fluoride in Tea , this series).

The rate of breast cancer in China is 18.7 per 100 000 women-years, 4 to 5 fold lower than in developed countries. But the rate had jumped by 50.5 percent between 1972 and 1994 in the now relatively affluent southeast of China.

Compared with an earlier sample of women drawn from the same area of southeast China in 1999-2000, the prevalence of tea consumption in controls in the present study had decreased by about 10 percent. This correlated with an increased incidence of breast cancer in the same population, suggesting that changes in lifestyle, including a trend away from the tradition of drinking green tea, are playing a role in raising breast cancer rates towards those of Western countries.

Prostate cancer in Italy

Researchers at the University of Modena and Reggio Emilia, Modena, Italy have demonstrated in a study involving a small number of high-risk subjects that up to 90 percent of prostate cancers could be prevented by taking a preparation of green tea catechins [9].

The incidence of prostate cancer has been steadily increasing in the United States and Europe, and is now the second leading cause of cancer-related deaths among men in western countries.

If the cancer is truly organ-confined, then radical prostatectomy, or radiation therapy are the main options. After the cancer has spread, hormonal therapy is most generally applied. But in nearly all men, advance cancer of the prostate eventually becomes refractory to hormonal therapy. Because of the unfavourable prognosis, early detection at potentially curable stages makes sense, but screening has never been shown to decrease mortality. Prevention is thus the best approach.

Several epidemiological studies have found lower incidence of prostate cancer in Asian countries where green tea is consumed regularly, as compared with Western populations. However, the risk for prostate cancer in Asian immigrants to the US increases to that of the host country if they abandon their original dietary habits. Recently, a case-control study in China showed that green tea consumption is inversely associated with prostate cancer, suggesting protective effects [10].

In order to obtain results quickly, the researchers focussed on men with high-grade prostate intraepithelial neoplasia (HG-PIN) (a clinical precancerous state). From previous research, it is known that a substantial number of them would develop prostate cancer within one year after repeated biopsy.

The green tea catechins preparation was assessed by high performance liquid chromatography to contain epigallocatechin (EGC) 5.5 percent, epicatechin (EC) 12.24 percent, epigallocatechin-3-gallate (EGCG), 51.88 percent, epicatechin-3-gallate (ECG) 6.12 percent, total green tea catechins (GTCs), 75.7 percent, and caffeine, less than 1 percent. This mixture is about what you would get in a cup of green tea.

Sixty volunteers with HG-PIN were enrolled in a double-blind, placebo-controlled study. Daily treatment consisted of three GTC capsules, 200 mg each.

After one year, only one tumour was diagnosed among the 30 GTC-treated men (incidence ~3 percent), whereas nine cancers were found among the 30 placebo-treated men (incidence 30 percent). GTC treated men also scored higher with respect to quality of life, and suffered no significant side effects or adverse effects. Furthermore, there were reduced urinary tract symptoms in the treated group.

This study showed that up to 90 percent of prostate cancers were prevented in men at high risk of developing it.

Hard to pin down the anticancer molecules

Many studies have demonstrated that tea flavonoids and tea can inhibit the growth of a variety of cancer cells and induce cell death via multiple cellular and molecular mechanisms [2]. This poses a challenge to the conventional Western medical model in which drug targets are specific enzymes or proteins, different for each disease.

In an attempt to better define the biological activity of different tea compounds, the US Department of Agriculture, California, and several universities in South Korea (Keimyung University, Daegu, Yeungnam University, Gyeongsan, and Uiduk University, Gangdong) joined forces to investigate the effect of individual tea flavonoids and total tea extracts on several human cancer cell lines as well as normal cell lines [11].

Nine green tea catechins, three black tea theaflavins and the aminoacid theanine (see Green Tea, The Elixir of Life? [2], for the chemical formulas of tea flavonoids), and extracts of 15 commercial teas, made either with boiling water for 5 min or with 80 percent ethanol/water at 60 C for 15 min, were evaluated for their ability to induce cell death in human cancer and normal cells.

Most of the catechins, all theaflavins, and theanine, were effective in reducing the number of human cancer cells when added to the cell culture, and all tea extracts were also effective. The cancer cells were: breast (MCF-7), colon (HT-29), hepatoma (liver (HepG2), and prostate (PC3). Normal human liver cells (Chang) were also susceptible, though not to the same degree as cancer cells, normal human lung cells (HEL299) were not affected.

However, the cell-destroying effects of tea compounds and tea extracts occurred at rather high, non-physiological concentrations from 50 to 400 m g/mL for the tea compounds, and from 40 to 400 m g/mL of tea solids for the tea extracts. Ethanol extracts with higher levels of flavonoids were often more active than the corresponding water extracts, but a substantial number of water extracts were more active in destroying cancer cells even though they contained less flavonoids. Different cancer cells also varied in their susceptibilities to destruction. There was no direct correlation between flavonoid levels of the teas and their ability to destroy cancer cells.

The difficulty in pinning down the molecules preventing cancer is not the dearth of molecular mechanisms identified, quite the opposite is the case; there is a bewildering array of cellular and molecular mechanisms through which tea flavonoids act [2, 12], but choosing one mechanism rather than another as the drug target in accordance with the conventional western medical model is the problem. The difficulty is compounded by the low levels of tea flavonoids that actually get through the gut into the bloodstream. It could be the mixture of flavonoids, or indeed the combination of flavonoids and other compounds that's responsible for cancer prevention.

The problem lies with the questionable basic assumption of the reductionist western medical model - that drugs should have specific molecular targets - which is seriously challenged by traditional Chinese medicine [13, 14] ( Traditional Medicine in Contemporary China , Traditional Chinese Medicine and Contemporary Western Science , SiS 18), and green tea is very much part of that tradition. It should by no means prevent people from accepting the evidence in favour of the health benefits of drinking green tea.

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