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Flavonoids and Heart Health: Proceedings of the ILSI North America Flavonoids Workshop

This article gives an overview of the knowledge of flavonoids as presented on the workshop entitled "Flavonoids and Heart Health" in 2005 and organized by the International Life Science Institute. The aim of the workshop was to establish the relationship between flavonoids intake and heart health, to determine recommended daily intake and to determine future research priorities.

Flavonoids are phytochemicals belonging to the group of phenolics. Other phenolics are tannins, coumarins and phenolic acids. More than 5000 flavonoids have been identified. They consists of 2 aromatic rings linked by a 3-carbon chain that forms an oxygenated heterocyclic ring. Flavonoids are further divided into five groups: flavonols, flavones, flavanones, flavan-3-ols and anthocyanins. Most flavonoids occur in plants as glycosides, meaning that they are bound to sugar molecules. Flavonols are the most widespread flavonoids in plants. Some well known flavonols are quercetin and kaempferol. Flavonols can be found in many common foods such as onions, leeks, broccoli, red grapes, apples and blue berries. Flavones, such as luteolin and apigenin, are less common and can be found in green vegetables such as celery and parsley. Flavanones are mainly found in citrus fruits, in the juice but also the albedo. Isoflavones are also called plant estrogens because of their structural similarity to human estrogen. They are mainly found in soybeans. Flavan-3-ols, such as epicatechin, epicatechin gallate, gallocatechin and catechin, are present in a variety of foods such as tea, cacao en fruits. Anthocyanins are the water-soluble pigments which give the typical colour to fruits and vegetables such as blue berry, strawberry, red wine and cabbage.

The bioavailability and metabolism of flavonoids are important factor in determining their efficacy. Some flavonoids such us anthocyanins are easily absorbed in the stomach whereas most other flavonoids are only absorbed in the intestine. Enzymes released by the intestinal epithelium or by intestinal bacteria may change the chemical structure of flavonoids. Their metabolites are finally excreted in the bile or urine.

It is very difficult to estimate the total consumption of flavonoids because their content in foods shows large variations. The flavonoids intake can be calculated from food composition tables are can be estimated by measuring biomarkers. Most food consumption tables do not show data about flavonoids or other phytochemicals. The USDA has on its website comprehensive tables of flavonoids (flavonols, flavones, flavanones, flavan-3-ols and anthocyanidins), proanthocyanidins and isoflavones of many foods. It is estimated that that Americans consume daily about 1 g of polyphenols, most of which is coming from tea, red wine, fruits, cacao, vegetables and legumes. The intake of individual flavonoids can show large differences between different population groups. For example, Japanese adults consume about 25 times more isoflavones that Western adults.

Flavonoids are well for their health benefits but they may also have adverse effects, such as antinutritional effects, thyroid toxicity, carcinogenic, development effects and drug interaction. Because many foods are rich in flavonoids they are generally recognized as safe. Very high intakes of flavonoids have been associated with antinutritional effects, such as reduced intake of glucose or minerals. However, the slower absorption of glucose may protect against diabetes mellitus. Some flavonoids have an effect on the thyroid function: they inhibit thyroid peroxidase and interfere with the production of the thyroid hormone. Soy isoflavones can in theory increase the risk of thyroid cancer but some studies have shown that the intake of isoflavones actually decrease the risk of thyroid cancer. In vitro studies, using quite high levels of flavonoids, demonstrate some carcinogenic and genotoxic effects, but these effects are not likely to occur in vivo. There were early reports that the intake of high quantities of isoflavones (from red clover) and coumestrol by cattle and sheep caused infertility. Such effects have not been observed in primates. Epidemiological studies show no effect of isoflavones on fertility, miscarriage, abortion or ectopic pregnancy.

Epidemiological studies and scientific experiments suggest a protective function of flavonoids against cardiovascular diseases. The effects of tea and red wine on cardiovascular disease have been studied intensively. It is estimated that the extra daily consumption of 3 cups of tea reduce reduces the risk of cardiovascular risk by more than ten percent. Epidemiological studies also show a relationship between red wine intake and cardiovascular protective effect. Flavonoids act by inhibiting the initiation and progression of atherosclerosis. The high intake of flavonoids by the French explains the French paradox, which refers to the observation that the French have lower rates of heart attacks despite the fact that they consume high amounts of saturated fats.

The effects of flavonols, flavones, flavanones and flavan-3-ols have been investigated in some large epidemiological studies. Most studies show a protective effect for these phytochemicals. However, one English study showed an inverse relationship between intake of cardiovascular disease and flavonols and flavones. This could be attributed to the fact that the English consume tea with large quantities of milk, which might inhibit the absorption of flavonoids. More studies are required to prove the clinical effect of these flavonoids. Isoflavones form another group of well studied flavonoids. They can bind selectively with estrogen receptors (alpha- and beta).

Animal experiments and epidemiological studies suggest that isoflavones protect against cardiovascular diseases such as atherosclerosis. They seem to directly improve the health of blood vessels. Isoflavones help to reduce LDL oxidation through their antioxidant activity.

Anthocyanins, the phytochemicals which gives many fruits it red or purple color, have also many claimed health benefits such as antioxidant, anti-inflammatory, antimicrobial, anticarcinogenic activities, neuroprotective effects, induction of apoptosis and improvement of vision. Many in-vitro studies have demonstrated the antioxidant effects of anthocyanins but the in-vivo effects are less evident because of the low absorption.

Proanthocyanidins and flavan-3-ols stimulate the release of NO, reduce the production of superoxide in aggregating platelets and reduce LDL oxidation. The antioxidant activity of proanthocyanidins and flavan-3-ols may be explained by their metal chelating properties.

This workshop concluded that studies only suggest that flavonoids reduce the risk of cardiovascular disease and more studies are required before it can be concluded that flavonoids actively reduce this risk.

Source: J. W. Erdman Jr., D. Balentine, L. Arab, G. Beecher, J. T. Dwyer, J. Folts, J. Harnly, P. Hollman, C. L. Keen, G. Mazza, M. Messina, A. Scalbert, J. Vita, G. Williamson and J. Burrowes. Flavonoids and Heart Health: Proceedings of the ILSI North America Flavonoids Workshop. Journal of Nutrition, March 1, 2007; 137(3): 718S - 737S

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