Flavonoids and Bioflavonoids

From the July 2007 edition of Dr. Fuhrman's Healthy Times:

Flavonoids and bioflavonoids mean the same thing. I will refer to them as flavonoids only. They refer to phytochemical compounds in plants that are absorbed by the body but then rapidly excreted as if they were a foreign substance, but without causing damage. Flavonoids do not function like conventional hydrogendonating antioxidants, but have an interesting hodgepodge of effects inside the cells. The hallmark of their unique properties is that they do not stay in the body very long and induce phase II detoxification enzymes in the liver, while at the same time attracting other toxins in the body to be expelled simultaneously. Flavonoids are like dust mops for toxins that get thrown out along with the dust that they collect.

Too Much of a Good Thing
Taking extra large amounts of supplemental flavonoids could be harmful, not helpful.Too many flavonoids, and especially too much of a single flavonoid, may not be health favorable.

For example, the potent antioxidant activity of epicatechin found in test tube chocolate may have very little, if any, antioxidant activity in the body because it is a flavonoid that is rapidly excreted by the body. The resveratrol found in grapes and red wine and the potent catechins in green tea may have powerful and beneficial effects, but if taken in concentrated dosages in a supplement form may do more harm than good.

Important Flavonoid Study
A team of University of California Berkeley (UC Berkeley) scientists led by C.F. Skibola and M.T. Smith has found that high concentrations of flavonoids in supplements sold at health stores actually may promote cancer formation. In a study of the impact of flavonoid intake on the cell, scientists 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 was published in the scientific journal Free Radical Biology and Medicine.6

Populations living in Japan show the highest levels of flavonol intake due to their high green tea consumption.“ Flavonoids found in foods are for the most part very beneficial for a variety of reasons,” Skibola said. “They can possess antioxidant, antiinflammatory, [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 20-80 grams of these isoflavones each day,while those in Western countries consume approximately one-three grams. Genistein is believed to have anticancer 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 estrogenic activity,” Skibola said. “We know that individuals who have more soy in their diets—typically individuals of Asian descent—have lower risk of hormonally-related cancers such as breast and prostate cancer.”

At low levels, estrogenic compounds, such as the phytoestrogens in soy, act like the estrogens synthesized naturally by the body. They outcompete the estrogens, thereby lowering the possibility for the estrogen to promote breast cancer. The phytoestrogens in soy compete with endogenous estrogens and inhibit a number of enzymes involved in estrogen metabolism. This is protective—by enhancing estrogen clearance through the body and altering the circulating forms of estrogen in the body to more favorable forms.

Supplement Problems

Along with the rising popularity of flavonoids has come a rise in production by the supplement industry, which has rushed to package and market flavonoids in the form of pills. At low concentrations, flavonoids help the body get rid of harmful free radicals and also promote the inhibition of enzymes like protein kinase, which is necessary in cell division. The effects of flavonoids are thought to be potentially anticarcinogenic 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. This is one reason flavonoids can be considered anticarcinogens. But even with all of the benefits that flavonoids provide the body, a great danger lies in overconsumption of the chemicals, the UC Berkeley 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 500-1000 milligrams of flavonoids each day in his or her diet. Popular flavonoid supplements, such as ginkgo biloba, usually contain 10-20 times more than the amount recommended for the human body in one pill. There exists a common misconception that if something is good, then much more is better. This false understanding may cause individuals who are looking for health benefits to ingest dangerously high levels of these compounds in isolated forms. The high levels and the unnatural delivery may create imbalances and effects that are unexpected. “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 the metabolism of drugs and 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, inhibiting enzymes such as DNA topoisomerase, which could lead to DNA breaks that potentially lead to cancer. “Thus,” the researchers said,“ 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 diet rich in high-nutrient plant foods.”

Natural Not Necessarily Safe
Just because something comes from a natural source doesn’t mean it can’t hurt you. For example, Skibola and Smith found that excessive intake of flavonoids may dangerously harm a growing fetus 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 fruits and vegetables contain flavonoids. If your diet were 100% from flavonoid-rich fruits and vegetables, you would get only the beneficial effects. The problem lies in using flavonoid concentrates produced by pharmaceutical and nutriceutical companies who are producing supplements of these substances in amounts 20-100 times as high as could be achieved from natural foods. The amount of flavonoids consumed by even strict vegetarians eating all healthful plants comes nowhere near the dangerous concentrations in supplements, the 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.’”

Combining Whole Foods
Combining cruciferous vegetables with other whole foods maximizes their beneficial effects. Scientific studies show that eating whole foods is more effective at fighting cancer than consuming extracts or individual components of those foods. The effectiveness is increased further when a variety of whole, nutrient-rich, natural foods is eaten at the same time. A recent study on rats illustrated this concept when a compound made of tomatoes and broccoli was compared to feeding them the powders made from extracts from either tomatoes or broccoli. The combination of tomatoes and broccoli was dramatically more effective at shrinking the prostate tumors (52% shrinkage) and showed the power of using food over supplements for cancer prevention and treatment. The group given lycopene (in powder form derived from tomatoes) showed an insignificant effect.7

Optimal benefits will occur from a diet rich in cruciferous vegetables. Include them in both raw and cooked forms from a variety of foods. These benefits cannot be duplicated by taking any one pre-formed compound or supplement. A consensus has been building for over a quarter of a century that a diet rich in fruits, vegetables, beans, and seeds is associated with lower risks of developing various types of malignancies.

The evidence is now overwhelming that cruciferous vegetables play a major and unique role in the widely recognized protective effects of natural plant foods against cancer— and are the most important player in this arena. The increased production of these biologically active compounds from raw vegetables is consistent with the studies that show a dramatically lower risk of cancer in those consuming more raw greens in their diet.8 For those in the know, these foods are the most important nutritional factors to prevent common human cancers.9
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2. Gamet-Payrastre L; Lumeau S; Cassar G. “Sulforaphane, a naturally occurring isothiocyanate, induces cell cycle arrest and apoptosis in HT29 human colon cancer cells.” Cancer Res 2000;60(5):1426-1433.

3. Cohen JH; Kristal AR; Stanford JL. “Fruit and vegetable intake and prostate cancer risk.” J Nat Can Inst 2000;92(1):61-68.

4. Gamet-Payrastre L; Li P, Lumeau S; et al. “Sulforaphane, a naturally occurring isothiocyanate, induces cell cycle arrest and apoptosis in HT29 human colon cancer cells.” Cancer Res 2000;60:1426-1433.

5. Brandi G; Schiavano GF; Zaffaroni N; et al. “Mechanisms of action and antiproliferative properties of Brassica oleracea juice in human breast cancer cell lines.” J Nutr 2005;135(6):1503 9.

6. Skibola CF; Smith MT. “Potential health impacts of excessive flavonoid intake.” Free Radic Biol Med 2000;29:375-383. Galati G; O'Brien PJ. “Potential toxicity of flavonoids and other dietary phenolics: significance for their chemopreventive and anticancer properties.” Free Radic Biol Med 2004;37(3):287-303.

7. Canene-Adams K; Lindshield BL; Wang S; et al. “Combination of tomato and broccoli enhance antitumor activity in dunning r3327-h prostate adenocarcinomas.” Cancer Res 2007;67(2): 836-43.

8. Link LB; Potter JD. “Raw versus cooked vegetables and cancer risk.” Cancer Epidemiol Biomarkers Prev 2004;13(9):1422-35.

9. Miller AB. “Nutritional aspects of human carcinogenesis.” IARC Sci Publ 1982;(39):177-92.
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LLouise - August 10, 2007 8:01 PM

Hi, Dr. F.

Would the extracts in your LDL be harmful? It was suggested that these would be okay for those without cholesterol issues as well.


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