"Drinking green tea still is good for you," said Yu-Dong Zhou, a molecular biologist at the university's National Center for Natural Products Research. "There are thousands of years of evidence on that, but the idea of taking the equivalent of hundreds of cups of tea a day is something that needs to be looked at carefully."

Zhou is principal investigator on a study that examined the effect of high doses of the active ingredients in green tea extract on hypoxia-inducible factor-1 (HIF-1), a key regulator of how tumor cells adapt to low-oxygen conditions. The results were published in a recent issue of the Journal of Natural Products.

Green tea is a popular beverage throughout much of the world and has been used medicinally for centuries in China and India. In areas where people drink a lot of green tea, there is a lower incidence of heart disease and some cancers.

In recent years, several manufacturers have produced dietary supplements containing concentrated extracts of green tea's active ingredients.

The compounds are not toxic in large doses, but high concentrations may not necessarily be healthful, explained Dale Nagle, associate professor of pharmacognosy in the UM School of Pharmacy who worked with Zhou on the project. Many commercial supplements provide far more of the active compounds than a person could obtain by simply drinking tea.

"Nearly all the evidence of the beneficial effects of green tea comes from studies on populations who consume green tea, not tea extract in the form of powder, concentrates or pills," Nagle explained. "There is no direct evidence that taking reasonable quantities of these green tea products is toxic. But the issue here is whether these extremely high doses are really beneficial.

"The fact that the green tea ingredient known as ECG activates HIF-1 -- which can have different effects depending on the type of tumor -- means it may not have the desired effect that people think they're getting."

The active compounds in green tea could actually serve dual functions, inhibiting HIF-1 at low concentrations and activating it at higher doses, Zhou said.

"At low concentrations, it doesn't seem to have this potentially negative effect as we saw in the lab," she said. "A lot more study needs to be done to see what the outcome will be in people who take high doses of these compounds."

"In theory, this effect on HIF-1 could suppress some early forms of tumors but may actually help other tumors -- especially some of the more aggressive ones -- survive and grow," Nagle said.

Zhou began studying green tea compounds more than three years ago, originally because they are touted as having antioxidant properties.

"We ran the experiment looking for one thing and found something totally different," she said.

The project was funded initially by the UM Office of Research and Sponsored Programs through its Faculty Research Fellows program. Additional support for this research has come from the Department of Defense's Breast Cancer Research Program and the National Cancer Institute.

Cautioning that the results are preliminary -- the study was performed using cultured cells in test tubes -- Zhou noted that taking extremely high doses of any dietary supplement is worrisome to researchers.

"We can't really tell people for sure what will happen when they take these high doses," she said. "Our best advice is to be careful. This needs to be studied carefully, and it will take time to determine what the actual overall effects are."