Flavonoids

Also indexed as: Bioflavonoids

What are they?

Flavonoids are a class of water-soluble plant pigments. Flavonoids are broken down into categories, though the issue of how to divide them is not universally agreed upon. One system breaks flavonoids into isoflavones, anthocyanidins, flavans, flavonols, flavones, and flavanones.¹ Some of the best-known flavonoids, such as genistein in soya, and quercetin in onions, can be considered subcategories of categories. Although they are all structurally related, their functions are different. Flavonoids also include hesperidin, rutin, citrus flavonoids, and a variety of other supplements.

While they are not considered essential nutrients, some flavonoids support health by strengthening capillaries and other connective tissue, and some function as anti-inflammatory, antihistaminic, and antiviral agents. Quercetin has been reported to block the "sorbitol pathway" that is linked to many problems associated with diabetes. Rutin and several other flavonoids may also protect blood vessels.

As antioxidants, some flavonoids, such as quercetin, protect LDL ("bad") cholesterol from oxidative damage. Others, such as the anthocyanidins from bilberry, purple cabbage, and grapes, may help protect the lens of the eye from cataracts. Animal research suggests that naringenin, found in grapefruit, may have anticancer activity.² Soya isoflavones are also currently being studied to see if they help fight cancer.

In a small, preliminary trial, rutoside (500 mg twice daily), a derivative of the flavonoid, rutin, combined with vitamin C (500 mg twice daily) produced marked improvement in three women with progressive pigmented purpura (PPP), a mild skin condition.³ Although not a serious medical condition, cosmetic concerns lead persons with PPP to seek treatment with a variety of drugs. The vitamin C/rutoside combination represents a promising, non-toxic alternative to these drug treatments, but larger, controlled trials are needed to confirm these preliminary results.

Where are they found?

Flavonoids are found in a wide range of foods. For example, flavanones are in citrus, isoflavones in soya products, anthocyanidins in wine and bilberry, and flavans in apples and tea.

Flavonoids have been used in connection with the following conditions (refer to the individual health concern for complete information):

Science Ratings	Health Concerns
	Chronic venous insufficiency (rutin) Hepatitis (catechin) Oedema (water retention) (coumarin, hydroxyethylrutosides)
	Bruising Cold sores Diabetes (bilberry) Dysmenorrhoea (rutin plus vitamin B3 [niacin] and vitamin C) Gingivitis (periodontal disease) (in combination with vitamin C) Haemorrhoids (hydroxyethylrutosides derived from rutin) Ménière’s disease (hydroxyethylrutosides) Oedema (water retention) (diosmin and hesperidin combination) Retinopathy (bilberry) Skin ulcers (diosmin, hesperidin)
	Allergies Atherosclerosis (quercetin, bilberry) Cancer (naringenin) Capillary fragility (hesperidin, quercetin, rutin) Cataracts (quercetin, bilberry) Diabetes (quercetin) Gingivitis (periodontal disease) Glaucoma (rutin) Hay fever (quercetin, hesperidin, rutin) Macular degeneration (bilberry) Measles Menopause (hesperidin) Menorrhagia (heavy menstruation) Night blindness (bilberry) Oedema (water retention) (quercetin) Peptic ulcer (quercetin) Progressive pigmented purpura (in combination with vitamin C) Retinopathy (quercetin, rutin)
Reliable and relatively consistent scientific data showing a substantial health benefit. Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit. For a herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support and/or minimal health benefit.

Who is likely to be deficient?

Flavonoid deficiencies have not been reported.

How much is usually taken?

Flavonoid supplements are not required to prevent deficiencies in people eating a healthy diet. Healthcare practitioners commonly recommend 1,000 mg of citrus flavonoids taken one to three times per day. Alternatively, 240–600 mg of bilberry (standardized to 25% anthcyanosides) may be taken per day.

Are there any side effects or interactions?

No consistent side effects have been linked to the flavonoids except for catechin, which can occasionally cause fever, anaemia from breakdown of red blood cells, and hives.⁴ ⁵ These side effects subsided when treatment was discontinued.

In 1980, quercetin was reported to induce cancer in animals.⁶ Most further research did not find this to be true, however.⁷ ⁸ While quercetin is mutagenic in test tube studies, it does not appear to be mutagenic in animal studies.⁹ In fact, quercetin has been found to inhibit both tumour promoters¹⁰ and human cancer cells.¹¹ People who eat high levels of flavonoids have been found to have an overall lower risk of getting a wide variety of cancers,¹² though preliminary human research studying only foods high in quercetin has found no relation to cancer risk one way or the other.¹³ Despite the confusion, in recent years experts have shifted their view of quercetin from concerns that it might cause cancer in test tube studies to guarded hope that quercetin has anticancer effects in humans.¹⁴

The flavonoids work in conjunction with vitamin C. Citrus flavonoids, in particular, improve the absorption of vitamin C.¹⁵ ¹⁶

Are there any drug interactions?
Certain medicines may interact with flavonoids. Refer to drug interactions for a list of those medicines.

References
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1. Peterson J, Dwyer J. Taxonomic classification helps identify flavonoid-containing foods on a semiquantitative food frequency questionnaire. J Am Diet Assoc 1998;98:682-5.

2. So FV, Guthrie N, Chambers AF, et al. Inhibition of human breast cancer cell proliferation and delay of mammary tumorigenesis by flavonoids and citrus juices. Nutr Cancer 1996;26:167-81.

3. Reinhold U, Seiter S, Ugurel S, Tilgen W. Treatment of progressive pigmented purpura with oral bioflavonoids and ascorbic acid: an open pilot study in 3 patients. J Am Acad Dermatol 1999;41(2 Pt 1):207-8.

4. Bar-Meir S, Halpern Z, Gutman M, et al. Effect of (+)-cyanidanol-3 on chronic active hepatitis: a double-blind controlled trial. Gut 1985;26:975–9.

5. Conn HO. Cyanidanol: will a hepatotrophic drug from Europe go west? Hepatology 1983;3:121–3 [review].

6. Pamukcu AM, Yalciner S, Hatcher JF, Bryan GT. Quercetin, a rat intestinal and bladder carcinogen present in bracken fern (Pteridium aquilinum). Cancer Res 1980;40:3468–72.

7. Hirono I, Ueno I, Hosaka S, et al. Carcinogenicity examination of quercetin and rutin in ACI rats. Cancer Lett 1981;13:15–21.

8. Saito D, Shirai A, Matsushima T, et al. Test of carcinogenicity of quercetin, a widely distributed mutagen in food. Teratog Carcinog Mutagen 1980;1:213–21.

9. Aeschbacher H-U, Meier H, Ruch E. Nonmutagenicity in vivo of the food flavonol quercetin. Nutr Cancer 1982;2:90.

10. Nishino H, Nishino A, Iwashima A, et al. Quercetin inhibits the action of 12-O-tetradecanoylphorbol-13-acetate, a tumor promoter. Oncology 1984;41:120–3.

11. Kuo SM. Antiproliferative potency of structurally distinct dietary flavonoids on human colon cancer cells. Cancer Lett 1996;110:41–8.

12. Knekt P, Jävinen R, Seppänen R, et al. Dietary flavonoids and the risk of lung cancer and other malignant neoplasms. Am J Epidemiol 1997;146:223–30.

13. Hertog M, Feskens EJM, Hollman PCH, et al. Dietary flavonoids and cancer risk in the Zutphen Elderly Study. Nutr Cancer 1994;22:175–84.

14. Stavric B. Quercetin in our diet: from potent mutagen to probable anticarcinogen. Clin Biochem 1994;27:245–8.

15. Vinson JA, Bose P. Comparative bioavailability to humans of ascorbic acid alone or in a citrus extract. Am J Clin Nutr 1988;48:601–4.

16. Vinson JA, Bose P. Comparative bioavailability of synthetic and natural vitamin C in guinea pigs. Nutr Rep Int 1983;27:875–9.

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The information presented in Healthnotes is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or chemist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires March 2007.

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