点击显示 收起
We see the converse of that with tea and cardiovascular disease, where there are some strong epidemiologic implications of a preventive effect. I think it has not been proven that we have a protective effect for any single site based on the epidemiologic evidence.
Dr Mukhtar: Most populations drink tea differently. In epidemiologic observations, it is difficult to control for that. In the published study [Ahmad N, Feyes DK, Nieminen AL, Agarwal R, Mukhtar H. Green tea constituent epigallocatechin-3-gallate and induction of apoptosis and cell cycle arrest in human carcinoma cells. J Natl Cancer Inst 1997;89:1881–6], a negative association was found for lung and other cancers, but part of that was attributed to the tea drinkers eating more fruits and vegetables and smoking less. This, in fact, was challenged. I agree that more studies are needed to better define the relation for human cancers.
Dr Watson: Many people use tea as a drink and not as a polyphenol source. They would be getting in 3 or 4 cups a day, 150–200 mg of caffeine. Can you briefly summarize some of the problems associated with caffeine, such as central nervous system complications and heart disease? Also, what about the effects of caffeine use during pregnancy?
Dr Mukhtar: I cannot comment on all of that. Studies from the laboratory of Dr Allan Conney suggest that a lot of the beneficial effects that we are observing from tea could be, in part, related to caffeine provided by tea.
Dr Milner: I had green tea for breakfast, lunch, and dinner for a month in Japan 2 y ago, and I don't think it was prepared the same way at any 2 meals. So it does not surprise me that the results of the epidemiologic studies are not consistent. Processing of tomatoes has a big impact on the response to them. I don't think we have an adequate idea of the impact of processing.
Dr Weisburger: I would second what Dr Mukhtar suggests. Some of the effects of tea may be attributable to its caffeine content. I have data that indicate caffeine is antimutagenic and protects against certain mutagens; it acts almost like an antioxidant [Weisburger JH, Dolan L, Pittman B. Inhibition of PHIP mutagenicity by caffeine, lycopene, daidzein, and genistein. Mutat Res 1998;416:125–8].
About 30% of Americans are sensitive to the cumulative effects of caffeine, 60–70% are not. If you have a heart condition, caffeine may stimulate your contractions, but I think that if you are consuming the right kind of diet, caffeine won't have an effect. The only adverse effect of caffeine is that those who are sensitive to it sleep poorly if they consume it late in the day. We should add that black tea and green tea have similar biochemical, physiologic, and epidemiologic effects and that we do need more human data.
The lung cancer rate is considerably lower in Japan than in the United States. In China, gastric and esophageal cancer rates are higher than in the United States, so we need more research on relations between these observations and tea drinking.
Dr Meydani: One additional point about the use of green or black tea is that the effects depend on the conditions under which it is used. For example, the British drink tea with milk in it. Evidence suggests that bioavailability of tea flavonoids may decline quite a bit under those conditions.
Dr Weisburger: It depends on how much milk you add. The International Standards Organization uses the standard of 1.85% milk in tea. We found in several models that adding milk increases the antitumorigenic effect of tea. We have been discussing many different foods here without asking the question how much.
Dr Beck: Dr Mukhtar, when you were talking about nuclear factor kappaB (NFB), which seemed to up-regulate a number of chemokines and cytokines, did you look at the role of NFB?
Dr Mukhtar: We have just started this work.
Dr Crowell: I agree that the preclinical animal data are fairly positive with regard to chemoprevention and that the epidemiologic observations can be interpreted both ways. That leads to the question of what we need to do next. The approach of our branch at the National Cancer Institute has been the placebo-controlled, randomized, blinded trial. Our strategy has been to take a single chemical entity, EGCG [epigallocatechin gallate], which is presumed to be the effective agent in tea. In another arm of the same trial, we are studying a well-defined polyphenol mixture that is fully characterized. The studies are conducted under an IND [Investigational New Drug] application with the Food and Drug Administration. In this way, the active principles may be identified based on modulation of pharmacologic or histologic markers.
Dr Milner: Do you know that NFB protein is modified by an amine?
Dr Mukhtar: It is modified by many antioxidants.
Dr Milner: Are there interactions among those antioxidants?
Dr Mukhtar: Not to my knowledge.
Dr Green: Customs may have a lot to do with the dose of polyphenols that tea drinkers get. In Japan especially, they often drink green tea. They also use green tea powder, which I believe is a much more concentrated source. They make a little broth out of it.
Have you compared the percentage of extraction of these polyphenols from brewed tea? How much of a dose do you get from brewing tea as opposed to eating the leaves? That is basically what you do with green tea powder. Maybe that could account for some differences between groups.
Dr Mukhtar: Once we brewed the tea, we could determine up to 100 mg of EGCG.
Dr Green: What percentage of the total polyphenols in green tea do you extract by brewing?
Dr Mukhtar: Less than 10%.
Dr Dwyer: What about herbal teas? Sassafras tea, of course, was taken off the market years ago because reputedly it was a liver carcinogen. What about some of the herbal teas that are becoming more and more common? Are they beneficial or detrimental?
Dr Mukhtar: Nobody knows because no one has studied them. What is herbal tea? You mix something with the tea leaves and you have herbal tea—so one more complexity is added.