Studies Force New View On Biology Of Flavonoids

However, these same compounds may indeed benefit human health, but for reasons that are quite different -- the body sees them as foreign compounds, researchers say, and through different mechanisms, they could play a role in preventing cancer or heart disease.

Based on this new view of how flavonoids work, a relatively modest intake of them -- the amount you might find in a healthy diet with five to nine servings of fruits and vegetables -- is sufficient. Large doses taken via dietary supplements might do no additional good; an apple a day may still be the best bet.

A research survey, and updated analysis of how flavonoids work and function in the human body, were recently published in Free Radical Biology and Medicine, a professional journal.

"What we now know is that flavonoids are highly metabolized, which alters their chemical structure and diminishes their ability to function as an antioxidant," said Balz Frei, professor and director of the Linus Pauling Institute. "The body sees them as foreign compounds and modifies them for rapid excretion in the urine and bile."

Flavonoids are polyphenolic compounds with some common characteristics that are widely found in fruits and vegetables and often give them their color -- they make lemons yellow and certain apples red. They are also found in some other foods, such as coffee, tea, wine, beer and chocolate, and studies in recent years had indicated that they had strong antioxidant activity -- and because of that, they might be important to biological function and health.

"If you measure the activity of flavonoids in a test tube, they are indeed strong antioxidants," Frei said. "Based on laboratory tests of their ability to scavenge free radicals, it appears they have 3-5 times more antioxidant capacity than vitamins C or E. But with flavonoids in particular, what goes on in a test tube is not what's happening in the human body."

Research has now proven that flavonoids are poorly absorbed by the body, usually less than five percent, and most of what does get absorbed into the blood stream is rapidly metabolized in the intestines and liver and excreted from the body. By contrast, vitamin C is absorbed 100 percent by the body up to a certain level. And vitamin C accumulates in cells where it is 1,000 to 3,000 times more active as an antioxidant than flavonoids.

The large increase in total antioxidant capacity of blood observed after the consumption of flavonoid-rich foods is not caused by the flavonoids themselves, Frei said, but most likely is the result of increased uric acid levels.

But just because flavonoids have been found to be ineffectual as antioxidants in the human body does not mean they are without value, Frei said. They appear to strongly influence cell signaling pathways and gene expression, with relevance to both cancer and heart disease.

"We can now follow the activity of flavonoids in the body, and one thing that is clear is that the body sees them as foreign compounds and is trying to get rid of them," Frei said. "But this process of gearing up to get rid of unwanted compounds is inducing so-called Phase II enzymes that also help eliminate mutagens and carcinogens, and therefore may be of value in cancer prevention.

"Flavonoids could also induce mechanisms that help kill cancer cells and inhibit tumor invasion," Frei added.

It also appears that flavonoids increase the activation of existing nitric oxide synthase, which has the effect of keeping blood vessels healthy and relaxed, preventing inflammation, and lowering blood pressure -- all key goals in prevention of heart disease.

Both of these protective mechanisms could be long-lasting compared to antioxidants, which are more readily used up during their free radical scavenging activity and require constant replenishment through diet, scientists say.

However, Frei said, it's also true that such mechanisms require only relatively small amounts of flavonoids to trigger them -- conceptually, it's a little like a vaccine in which only a very small amount of an offending substance is required to trigger a much larger metabolic response. Because of this, there would be no benefit -- and possibly some risk -- to taking dietary supplements that might inject large amounts of substances the body essentially sees as undesirable foreign compounds.

Numerous studies in the United States and Europe have documented a relationship between adequate dietary intake of flavonoid-rich foods, mostly fruits and vegetables, and protection against heart disease, cancer and neurodegenerative disease, Frei said.