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The cancer-fighting flavonoid chemicals in soy products have made the "vegetarian's meat" the latest health craze, but a team of UC Berkeley scientists have found that high concentrations of flavonoids in supplements sold at health stores may actually promote cancer formation.

In a study of the impact of flavonoid intake on the cell, UC Berkeley toxicology professor Martyn Smith and graduate student Christine Skibola have found that excessively high levels of flavonoids in the body can damage the chromosomes and DNA in cells, leaving them more susceptible to cancer.

Their study, published in the most recent scientific journal Free Radical Biology and Medicine, outlines and describes the role of plant flavonoids on the body's cells.

Flavonoids are the chemical compounds found in abundance in foods such as fruits, vegetables, teas, grains, coffee, beer, red wine and cola. Populations living in Japan show the highest levels of flavonol intake due to their high green tea consumption. Soy marketers have touted flavonoids for their anti-cancer effects and the chemicals have been increasingly lauded by health experts for their associated health benefits.

"(Flavonoids) have antioxidant properties and are thought to protect against damaging free radicals," Smith said. "Their mechanism of action is not well known, however."

Onions and apples have high quantities of flavonoids. In addition, soy has been praised as beneficial to the body because many vegetarians use it to replace meat in their diet and studies have shown that populations with diets high in soy, such as the Japanese, exhibit lower cancer rates.

"Flavonoids found in foods are for the most part very beneficial for a variety of reasons," Skibola said. "They can possess antioxidant, anti-inflammatory, (and) anti-proliferative activity."

The ingredients in tofu and soybean that are thought to decrease the rate of cancer are the isoflavones genistein and diadzein. Populations in Asian countries consume approximately 20 to 80 grams of these isoflavones each day while those in Western countries consume approximately one to three grams. Genistein is believed to have anti-cancer effects because it can act as an estrogen antagonist, which inhibits the reaction that estrogen has on cells.

"Soy contains phytoestrogens which are compounds with weak estrongenic activity," Skibola said. "We know that individuals who have more soy in their diets - typically individuals of Asian decent - have lower risk of hormonally-related cancers such as breast and prostate cancer."

Estrogens comprise a family of steroid hormones that regulate and sustain female sexual development and reproductive function. In some recent studies, the hormone has been linked to increased risk of breast cancer. At low levels, estrogenic compounds such as the phytoestrogens in soy act like the estrogens synthesized naturally by a body and outcompete the estrogens, thereby lowering the possibility for the estrogen to promote breast cancer.

"The phytoestrogens in soy are thought to compete with endogenous estrogens, as well as inhibit a number of enzymes involved in estrogen metabolism," Skibola said. "This may be protective by enhancing estrogen clearance through the body and altering the circulating forms of estrogen in the body."

Along with the rising popularity of flavonoids has been a rise in production by the supplement industry, which has rushed to package and market flavonoids in the form of pills to be sold in health stores.

At low concentrations, flavonoids help the body get rid of harmful free radicals and also promotes the inhibition of enzymes like protein kinase, which is necessary in cell division. The effects of flavonoids are thought to be potentially anti-carcinogenic because flavonoids can block and inhibit the excessive cell division characterized by cancer.

"Certain flavonoids can inhibit enzymes such as protein kinases, that are involved in cellular proliferation and tumor progression," Skibola said. "This is one reason flavonoids can be considered anti-carcinogens."

Even with all the benefits that flavonoids provide the body, a great danger lies in overconsumption of the chemicals, the scientists said. Although phytoestrogens are not as potent as endogenously produced estrogens, excess amounts of these compounds can actually promote breast cancer and feminize males.

According to the scientists, the average person in the United States consumes approximately 500 to 1000 milligrams of flavonoids each day in his or her diet. Popular flavonoid supplements such as ginkgo biloba usually contain 10 to 20 times more than the amount recommended for the human body in one pill.

"The point is one or two aspirin cures a headache, but 40 could kill you," Smith said.

There exists a common misconception that if a little of something is good then more is better, the scientists said. This false understanding may cause individuals who are looking for health benefits to dangerously ingest extremely high levels of these compounds.

"At high concentrations, certain flavonoids can act as pro-oxidants and become mutagenic meaning that they could cause oxidative damage and cause DNA and chromosome damage," Skibola said. "They also can inhibit a number of enzymes that can alter normal body functions. They can interfere with metabolism of drugs and they can interfere with mineral absorption in our bodies."

When consumed in excessive quantities, flavonoids act as mutagens and contribute to free radical formation. They can damage DNA, break chromosomes, and act as endocrine disrupters and inhibit enzymes such as DNA topoisomerase, which could lead to DNA breaks that potentially lead to cancer.

"At higher doses, flavonoids may act as mutagens, pro-oxide that generate free radicals, and as inhibitors of key enzymes involved in hormone metabolism," the scientists reported. "Thus, in high doses, the adverse effects of flavonoids may outweigh their beneficial ones, and caution should be exercised in ingesting them at levels above that which would be obtained from a typical vegetarian diet."

In their study, Skibola and Smith found that the potentially toxic effects of the supplement have not been understood or highlighted.

"Just because something comes from a natural source doesn't mean it can't hurt you," Skibola said. "The dose makes the poison. Even drinking too much water can be harmful and unfortunately people tend to forget that. Many of our pharmaceuticals come from natural substances. We need to know that flavonoids at high doses can also have adverse effects."

The researchers also found that excessive intake may dangerously harm growing fetuses in a pregnant woman's body because flavonoids are small and readily cross the placental barrier between a mother and the child in her womb.

All of the research found that it is very important to continue eating fruits and vegetables.

"All fruits and vegetables contain flavonoids," Skibola said. "Remember, we are not saying to stay away from fruits and vegetables. They are so very good for us. I think individuals who eat lots of fruits and vegetables are getting a healthy, beneficial amount of flavonoids. Eat your fruits and vegetables. The problem lies in using flavonoid concentrates."

The amount of flavonoids consumed by even the strictest vegetarian comes nowhere near the dangerous concentrations in supplements, scientists said.

"There is no evidence that a veggie diet is harmful," Smith said. "You can't eat enough onions, soy, etcetera to harm yourself."

In light of the research, Smith and Skibola hope to convey a message to the supplement industry about the potential harm of excessive flavonoid uptake.

"(The supplement industry) needs to stop selling these potentially harmful products," Smith said. "Until these supplements are shown to be safe they should not be sold. If I were the FDA I would ban them. One of the mainstays of medicine is 'first do no harm.'"

The scientists are currently working to conduct further testing of the potentially beneficial and toxic effects of flavonoids.

"We are currently looking at the potential beneficial and adverse effects of these compounds in laboratory studies," Skibola said. "More research must be done to understand the toxicology of flavonoids. People don't understand the underlying activities of these compounds and they are underestimating their biological effects which are not always beneficial."

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