Flavonoids
What is it?
Flavonoids were discovered by Nobel Prize-winning biochemist Albert Szent-Gyorgi, who labeled them "vitamin P". He discovered that they enhanced the function of vitamin C, improving absorption and protecting it from oxidation. Flavonoids that have been shown to have particularly beneficial properties include proanthocyanidins, green tea polyphenols and soy isoflavones. Quercetin and its derivatives; the citrus bioflavonoids, including quercitrin, rutin and hesperidin; have also been fairly well studied.
What it does in the body
Cardiovascular system
Flavonoids are important for blood vessel health. They regulate capillary permeability, thereby stopping fluid, protein and blood cells from seeping out while still allowing oxygen, carbon dioxide and other nutrients to pass through. Many flavonoids enhance capillary strength, preventing them from being easily bruised. This is partly due to the vitamin C-enhancing action of flavonoids. This may help protect against infection and blood vessel diseases.
Flavonoids can also relax the smooth muscle of the cardiovascular system, thus lowering blood pressure. This also improves circulation to the heart itself. Flavonoids are antioxidant and can also prevent oxidation of harmful LDL cholesterol, thereby preventing the build-up of atherosclerotic plaque. They may also stop blood platelets from clumping together which can help to reduce blood clotting and damage to blood vessels.
Anti-inflammatory effects
Flavonoids have anti-inflammatory properties. This is due to their antioxidant effects and to their ability to act against histamines and other mediators of inflammation, such as prostaglandins and leukotrienes.
Other effects
While flavonoids have many properties in common, specific compounds often have specific properties. Some may have estrogen-like activity while others inhibit tumor growth.
Absorption and metabolism
Flavonoids are usually easily absorbed from the intestine. Excesses are excreted in the urine.
Deficiencies
There are no reports of flavonoid deficiencies as most people seem to get enough in their diet to prevent this. It is possible, however, that many people do not eat enough for optimal health.
Sources
Flavonoids are found in the edible pulp of fruits such as citrus fruits, rose hips, apricots, cherries, grapes and blackcurrants. Green pepper, broccoli, onions and tomatoes are good vegetable sources and buckwheat is also a rich source. Green tea and red wine also contain several flavonoids. Many herbs are rich sources of flavonoids and these contribute to the therapeutic effects. These include bilberry, hawthorn, ginkgo, yarrow and milk thistle (See page 384 for more information.)
Recommended dietary allowances (RDA)
There are no recommended intakes for flavonoids.
Supplements
Bioflavonoid supplements are available in varying types and doses. Pine bark and grape seed extracts are sources of proanthocyanidins. The mix of these flavonoids, like other nutrients, varies from plant species to species. Both sources can be used interchangeably, but grape seed extract may have an advantage over pine bark. Most grape seed extracts contain 92 to 95 per cent proanthocyanidins, whereas pine bark extracts usually contain from 80 to 85 per cent. Grape seed extract also contains small quantities of a beneficial flavonoid found in green tea.
Toxic effects of excess intake
There are no known toxic effects of large intakes.
Therapeutic uses of supplements
Enhancement of vitamin C action
Flavonoids, particularly citrus bioflavonoids, are often given with vitamin C; for example in the treatment of colds, bleeding problems, bruising and ulcers. Flavonoids may also have antiviral activity.
Cardiovascular disease
As flavonoids have been shown to have antioxidant properties, they are able to protect against heart disease, which may explain the so-called 'French paradox.' This refers to the fact that the French eat much larger amounts of saturated fat and have higher cholesterol levels and blood pressures than Americans, yet are 2.5 times less likely to die of coronary heart disease.
Red wine is a good source of flavonoids and many people have suggested that the liberal French consumption of red wine protects against coronary heart disease. Several studies have found that a glass or two of wine daily protects against heart disease and it seems likely that red wine is more protective than white wine, suggesting that the benefits might be unrelated to the alcohol.
Researchers involved in the Zutphen elderly study assessed the flavonoid intakes of 805 men aged from 65 to 84 years in 1985. The major sources of flavonoid intake were found to be tea, onions, and apples. The men were then followed up for five years, during which time 43 men died of coronary heart disease. Fatal or nonfatal heart attacks occurred in 38 of 693 men with no history of heart attack at the beginning of the study. The results showed that those with the highest flavonoid intake had less than half the risk of death from heart attack when compared to those in the lowest intake group.1
In a 1996 study, Harvard researchers assessed the links between heart disease and flavonoid intake in 34 789 male health professionals aged from 40 to 75. Among the 4814 men who reported that they had previously had coronary heart disease, flavonoids showed a protective effect against death from heart attack.2
High flavonoid intakes also seem to protect against stroke. Researchers involved in a 1996 Dutch study assessed the diets of 552 men aged 50 to 69 years in 1970 and followed them up for 15 years. The results showed that those with the highest intakes of dietary flavonoids (mainly quercetin) had around 75 per cent less risk of stroke compared to those with the lowest intakes. Black tea contributed about 70 per cent of the flavonoid intake in the study. Men who drunk more than four cups of tea had around a third of the risk of stroke when compared to those who drunk less than two cups of tea.3 However, in a 1997 study done in Wales, researchers did not find a reduced risk of heart disease with increasing tea consumption.4 Black tea seems to be more effective in raising antioxidant levels than tea with milk.
Flavonoids are useful in the treatment of high blood pressure due to their capillary-strengthening and blood vessel-dilating effects. They are also useful in capillary fragility disorders such as easy bruising, bleeding of the gums, and also in circulatory disorders of the retina of the eye. They are particularly useful in the treatment of vein and capillary problems such as varicose veins, venous insufficiency (poor return of blood to the heart from the veins of the legs), and eye problems such as diabetic retinopathy and macular degeneration.
Green tea
Green tea contains several polyphenols, the most active of which appears to be epigallocatechin gallate. These compounds have several beneficial effects, including protection from heart disease.
Green tea has been shown to lower cholesterol. In a 1995 Japanese study researchers investigated green tea consumption of 1371 men aged over 40 years. Analysis of their blood samples showed that increased consumption of green tea was linked to decreased serum concentrations of total cholesterol and triglyceride, and increased levels of beneficial HDL cholesterol together with decreased levels of LDL and VLDL cholesterols. Those who drank ten or more cups per day showed better liver function measurements.5
Research from Japan has linked green tea consumption with a reduced risk of stroke. In a four-year study of almost 6000 women, the incidence of stroke and cerebral hemorrhage was at least twice as high in those who drank less green tea (fewer than five cups a day) than in those who drank more (greater than or equal to five cups daily).
Cancer
Flavonoids may also help to protect against cancer. Many laboratory experiments have shown that various flavonoids can inhibit the growth and proliferation of cancer cells. Recent animal experiments looking at tumor onset in mice found beneficial effects when their diets were supplemented with red wine solids (which contain no water or alcohol).
In a study published in 1997, Finnish researchers investigated the links between the intake of flavonoids and subsequent risk of cancer in 9959 Finnish men and women aged from 15 to 99 years and initially cancer-free. During the follow-up period, 997 cancer cases and 151 lung cancer cases were diagnosed. The results showed that a high intake of flavonoids reduced the risk of all types of cancer. An inverse association was observed between the intake of flavonoids and incidence of all sites of cancer combined. Those with the highest flavonoid intakes had almost half the risk of cancer compared to those in the lowest intake groups.6
Researchers involved in the Iowa Women's Health Study analyzed the tea drinking habits of over 35 000 postmenopausal women and found that those who drank more than two cups of tea a day were 32 per cent less likely to have cancers of the mouth, esophagus, stomach, colon and rectum. They were also 60 per cent less likely to have urinary tract cancer. In those who drank four or more cups per day, the risk of cancer was lowered by 63 per cent.7
Onions are high in flavonoids, which may explain the links between their consumption and reduced cancer risk. Researchers involved in The Netherlands Cohort Study assessed the links between onion consumption and the risk of stomach cancer in 120 852 men and women ranging in age from 55 to 69 years. Those whose onion intakes were high had around half the risk of stomach cancer when compared to those whose intakes were low.8
Green tea
Green tea preparations and extracts have been shown to inhibit tumor formation and growth in laboratory experiments. The evidence for the protective effect of green tea is strongest for cancers of the digestive tract.
Most of the research on the health benefits of green tea has been carried out in Japan and China. In a study published in 1997, Japanese researchers investigated the links between green tea and cancer in 8552 people over 40. During a follow-up period of nine years, there were 384 cases of cancer. The results showed a lower risk in those who drank green tea, especially among women drinking more than ten cups a day.9
The results of a Chinese study suggest that drinking green tea can reduce the risk of esophageal cancer. The study involved 902 patients, aged 30 to 74, who were diagnosed with cancer of the esophagus from October 1990 through January 1993. A group of 1552 healthy volunteers were used as controls. Histories of cancer in the family, diet, smoking and drinking habits were taken into account. The researchers found that for those who refrained from smoking or drinking alcohol, green tea consumption reduced the risk of esophageal cancer in men by 57 percent, and 60 per cent in women. For those who smoked or drank alcohol, green tea exerted little protection.10
Another Chinese study showed that drinking green tea also reduced the risk of stomach cancer. This study involved 711 patients and 711 controls. The results showed that those who drank green tea had 30 per cent less risk of stomach cancer.11 Other studies have shown reduced risks for colon cancer.12 Green tea may also protect against the carcinogenic changes caused by cigarette smoke.13
In a study published in 1998, Japanese researchers investigated the effects of drinking green tea on the progression of breast cancer. The study involved 472 patients with stage I, II, and III breast cancer. The results showed that increased consumption of green tea was linked to a decrease in the spread of breast cancer in premenopausal women. In a follow-up study, the researchers found that increased consumption of green tea was correlated with decreased recurrence of stage I and II breast cancer.14
Allergies and autoimmune disease
In addition to their antioxidant effects, the ability of flavonoids to affect enzymes involved in the production of inflammatory substances means they may be useful in the treatment of asthma, allergies, bursitis, arthritis and inflammatory bowel disease.
Quercetin
Quercetin has been shown to exert anti-inflammatory effects. Inflammation is mediated partly by the release of histamine from mast cells. Quercetin may stabilize the membranes of these cells, thereby reducing histamine release. It may also affect leukotriene synthesis.
Diabetes
Quercetin
Quercetin may inhibit the enzyme that converts glucose to sorbitol, a compound which is linked to diabetic complications, including cataracts (See page 593 for more information.) Quercetin-related compounds have been shown to inhibit cataract formation in diabetic animals. Quercetin may also enhance insulin secretion and protect pancreatic cells from free radical damage.
Soy
Soy contains types of flavonoid compounds known as isoflavones. These are also referred to as phytoestrogens because they have both estrogenic and anti-estrogenic properties. When circulating levels of estrogens are high, such as in premenopausal women, these compounds can bind to estrogen receptors and block action of the hormone. When estrogen levels are low, such as in postmenopausal women, phytoestrogens act estrogenically. Phytoestrogen compounds in soy include genistein and daidzein. Evidence from molecular and cellular biology experiments, animal studies, and human clinical trials suggests that phytoestrogens may help to prevent cardiovascular disease, cancer, osteoporosis, and menopausal symptoms. Epidemiological studies suggest that rates of these disorders are lower among populations that eat plant-based diets, particularly among cultures with diets that are traditionally high in soy products. Soybeans also contain other beneficial compounds including phytosterols, which have been shown to lower blood cholesterol, possibly by competing with cholesterol uptake.
Cardiovascular disease
Several studies have shown that the addition of soy foods or extracts to the diet lowers cholesterol. In a 1997 study, 17 healthy men and 17 healthy women with raised levels of total and LDL cholesterol were given either 2 per cent cows' milk products, soybean products or a combination of skim milk products and soy oil, over period of four weeks. During the soybean period, the subjects' mean level HDL cholesterol increased 9 per cent and their mean LDL/HDL cholesterol ratio decreased 14 per cent.15 Soy compounds may also reduce the oxidation of LDL cholesterol and inhibit clumping together of platelets, both of which slow the atherosclerotic process. They may also improve arterial function.
Cancer
Eating soy foods may lower the risk of cancers, particularly those that are hormone-dependent, such as breast and prostate cancer. Breast cancer rates are lower in countries with soy-based diets and soy products have been shown in many animal experiments to inhibit tumor growth. Genistein may block the stimulatory effect of estrogen on cancer cells. Other hormone-dependent cancers, such as prostate cancer, may also be affected by genistein, which appears to block enzymes that promote tumor growth. Genistein may also inhibit the growth of new blood vessels into tumors.
Researchers involved in a study published in 1997 examined the links between soy and endometrial cancer in 332 women diagnosed with endometrial cancer from various ethnic groups in Hawaii. Their diets were compared with 511 control subjects. High consumption of soy products and other legumes was associated with a decreased risk of endometrial cancer, with those in the high intake group having around half the risk of those in the low intake group.16 A 1996 US study showed a decrease in breast cancer risk in Asian American women who increased tofu intake.17
Menopause and osteoporosis
Japanese women appear to suffer fewer menopausal symptoms than Western women. One of the reasons may be their high consumption of soy foods. Soy compounds may also be useful in preventing osteoporosis which occurs when a decline in circulating estrogen leads to a reduction in bone mass. Estrogen-like compounds such as genistein can help to build bone.
In a 1998 double-blind, randomized placebo-controlled study Italian researchers investigated the effects of daily dietary supplementation of soy protein isolate powder on hot flashes in 104 postmenopausal women. Fifty-one patients took 60 g of isolated soy protein daily and 53 took 60 g of placebo daily. The study lasted 12 weeks. The results showed that soy was much better than placebo at reducing the average number of hot flashes per 24 hours after four, eight, and 12 weeks of treatment. By the end of the twelfth week, women taking soy had a 45 per cent reduction in their daily hot flashes versus a 30 per cent reduction obtained with the placebo.18