Getting Familiar With Flavonoids

Ever wonder what natural compounds account for the aroma, flavor and color of vegetables and fruits? The answer is flavonoids. Thousands of them.

Interest by the public in flavonoids has been increasing due to the growing reputation of food antioxidants that can have beneficial roles in disease prevention. The number of hits on Google for flavonoids is 2.52 million, and on PubMed, an online database just for medical research, there are over 34,000 original publications on flavonoids.

Flavonoids are a large family of phenolic compounds synthesized by plants as pigments that attract pollinators, repel pests and protect plant cells both from ultraviolet radiation and internal production of reactive oxygen species during photosynthesis.

As a group, flavonoids are the most associated phytochemical class with antioxidant values in plant foods.

Health scientists believe that people gain some of these same benefits by consuming flavonoid-rich plant foods, an area of active scientific study.

Current research trends on flavonoids

• Scientists are keenly pursuing numerous potential health effects of flavonoids associated with fruit and vegetable-rich diets. Even in people without disease, benefits may occur for the cardiovascular system, brain, joints, skin, and urinary tract.

• Many of the biological effects of flavonoids seem to come from their ability to modulate communication between cells, a new mechanism of flavonoid action in addition to the more traditionally accepted antioxidant activity.

• Scientists are examining flavonoids as "biological response modifiers", a role where they may alter the body's responses to viruses, allergens, bacteria, carcinogens (cancer agents), inflammatory agents, and oxygen radicals.

• Flavonoid intakes through the diet may help prevent cancer in humans.

• Flavonoid consumption may lower risk of neurodegenerative diseases, as in Alzheimer's or Parkinson's disease.

• While higher intakes of flavonoid-rich foods have been associated with reduced risk of some chronic diseases, it is not known whether isolated flavonoid supplements or extracts confer the same benefits as flavonoid-rich foods.

6 Major Classes of Dietary Flavonoids

Although flavonoids are related by a common chemical structure (called in chemistry, a "phenolic ring"), there are at least 4,000 variations in flavonoid structure and therefore more than 4,000 individual flavonoids in the plant kingdom. To manage such diversity, it is useful to group these compounds into 6 major classes, each having members with similar structure. The following groups have been devised by food chemists and give a place to start educating the public. The names of classes are similar because the chemical structures are closely related.

1. Anthocyanidins. Also called flavonals. Parent structure to anthocyanins found in red, blue, purple and black berries and grapes. Present in dark wines. Examples: cyanidin, delphinidin, petunidin, peonidin, malvidin, pelargonidin.

2. Flavanols. Found in black and green teas, berries, dark chocolate. Single structures ("monomers") are called catechins whereas multiple-unit structures ("polymers") are called proanthocyanidins, tannins, epigallocatechin, and theaflavins. May contain subgroups of ellagic or gallic acid. This class is also named flavan-3-ols.

3. Flavanones. Characteristic of citrus fruits (oranges, grapefruit, lemons), members of this group include naringenin, silybin and hesperidin.

4. Flavonols. Found in all plants with bright colors, such as berries, kale (dark green), broccoli and bell peppers, this group includes quercetin, kaempferol, myricetin, rutin and isorhamnetin.

5. Flavones. Represented by apigenin and luteolin, flavones are found in herbs (chamomille, parsley) and subterranean plants like celery and radishes.

6. Isoflavones. The signature group from soybeans and soy products (tofu, soy milk), isoflavone members include genistein and daidzein.

Less Antioxidant Activity Than We Hoped?

Due to their favorable chemical structure for serving as antioxidants, flavonoids are expected to be effective scavengers of free radicals in the human body, just as they are in the test tube ("in vitro").

However, even with very high flavonoid intake through the diet, blood and intracellular flavonoid concentrations in humans are around 100-1,000 times lower than concentrations of other known antioxidants, such as vitamin C, melatonin or glutathione. Part of this effect occurs because flavonoids do not stay in the blood or tissues, but are filtered by the kidneys into urine for excretion. Scientists would say from these circumstances that flavonoids are not very "bioavailable".

Also, it has been found that most circulating flavonoids are actually flavonoid substructures cleaved off from the parent molecule by stomach acids and metabolism. Naturally, some of these new, smaller flavonoid molecules have lower antioxidant activity than the parent.

For the reasons above, the relative contribution of dietary flavonoids to the body's antioxidant protection is less than predicted from their chemical structure and antioxidant activity in vitro.

Flavonoids Affect Communications Between Cells

Although initially thought that flavonoids would have antioxidant roles as their main biological function, new scientific evidence from cell culture research indicates that flavonoids can modify signaling activity between cells. Flavonoid concentrations needed to change cell signaling pathways are considerably lower than those required to serve antioxidant roles.

Changes in cell-to-cell signaling capability require enzymes known as kinases to sensitize target proteins ("receptors") at the receiving cell. Cell culture experiments indicate that flavonoids may affect chronic diseases by selectively inhibiting kinases.

This means that flavonoids may alter receptor sensitivity in certain diseases, such as in cancer by these candidate mechanisms:

1. Cancer cells depend on growth stimuli to enlarge and spread; flavonoids may inhibit cancer cells from communicating these signals to one another.

2. Cancer cells proliferate rapidly and lose their ability to undergo normal cell death signals ("apoptosis"; pronounced eh-poe-toe-sis); flavonoids may inhibit both the proliferation process and apoptosis.

3. Cancerous cells invade normal tissue aided by enzymes called matrix-metalloproteinases; flavonoids block the activities of these metal-containing enzymes.

4. Invasive tumors must also develop new blood vessels by a process known as angiogenesis to support their rapid growth; flavonoids inhibit angiogensis.

5. Tumor growth may depend on mechanisms of inflammation to grow, proliferate and resist apoptosis; flavonoids are well-established as anti-inflammatory agents.

Ongoing research will reveal additional characteristics of flavonoid biology in health and disease. It seems safe to conclude that the surest way consumers can gain the health rewards promised by flavonoid research is to consume plentiful plant foods containing them.

This should be an easy task as such foods are the most colorful and best-tasting fresh produce in the store -- Berries, red delicious apples, citrus fruits, black and green teas, red, orange, yellow and dark green vegetables, and even dark chocolate!

Reading

• Flavonoids, Micronutrient Information Center, Linus Pauling Institute, Oregon State University, http://lpi.oregonstate.edu/infocenter/phytochemicals/flavonoids/

• Database for the Flavonoid Content of Selected Foods, US Department of Agriculture, Nutrient Data Laboratory, http://www.nal.usda.gov/fnic/foodcomp/Data/Flav/flav.html

• PubMed, online database of the US National Library of Medicine, http://pubmed.gov

• Wikipedia on Flavonoids, http://en.wikipedia.org/wiki/Flavonoids

• Ross JA, Kasum CM. Dietary flavonoids: bioavailability, metabolic effects and safety. Annu Rev Nutr. 2002; 22:19-34.

• Joseph JA, Nadeau DA, Underwood A. The Color Code, Hyperion, 2002.