Flavonoids, also called bioflavonoids, are a group of naturally occurring compounds which are widely distributed in nature and are ubiquitous in vegetables, berries, and fruits... and fortunately in chocolate. Flavonoids comprise the most common subset of plant Polyphenols and provide much of the flavor and color to fruits and vegetables. More than 5000 different flavonoids have been identified. Citrus bioflavonoids are those flavonoids found in citrus fruits such as lemon, orange, tangerine, grapefruit, etc. Dietary intakes of flavanones, anthocyanidins, and certain foods rich in flavonoids are associated with reduced risk of death due to coronary heart disease and cardiovascular disease.

Flavonoids in Diet
The daily flavonoid intake in the human diet (mainly from onions, apples, grapes, wine, tea, berries, herbs, and spices) is highly variable, with estimations ranging from 25 mg to more than 500 mg.

Quercetin - A prominent Flavonoid
Source Naturals


Activated Quercetin is a unique bioflavonoid derived from plant sources. In human cell culture studies, Quercetin has been shown to inhibit histamine release. Additional research needs to be conducted to confirm the effects of Quercetin, if any, in humans. Bromelain is a pineapple enzyme that may assist the body in times of stress. Magnesium ascorbate is a buffered (non-acidic) form of vitamin C that helps support the immune system.


Quercetin Supplement Facts:
Vitamin C
Magnesium (as magnesium ascorbate)
Quercetin
Bromelain

Flavonoids daily value not established.

Click Flavonoids to purchase or to see a complete list of products at Physician Formulas
Subscribe to a FREE Supplement Research Update newsletter. Twice a month you will receive an email with a review of several studies on supplements and natural medicine topics, including flavonoids, and their practical interpretation by Ray Sahelian, M.D.

Eyesight Rx with Flavonoids
Supports Healthy Vision
Developed by Ray Sahelian, M.D.

Unlike some vision products that provide nutrients and herbs for long term healthy vision support, and prevention of visual impairment, but don't seem to have much of an immediate effect on visual acuity, Eyesight Rx was formulated to provide a quick and noticeable vision improvement within hours or days of use.

Reports from Eyesight Rx users indicate enhanced clarity of vision, colors being brighter, better focus, and overall improvement in close and distance vision. We've had reports of some people noticing this effect within a half hour, while most people notice improved vision within hours. Still others will realize their vision is sharper the next morning when they take their second dose.

Supplement Facts:
Vitamin C
Citrus bioflavonoids
     (eriocitrin, hesperidin, flavonols, flavones, flavonoids, naringenin, and quercetin)
Mixed carotenoids
     (alpha carotene, astaxanthin, beta carotene, cryptoxanthin, Lutein, Lycopene, Zeaxanthin)
Bilberry extract (Vaccinium myrtillus)
Eyebright extract (Euphrasia officianales)
Jujube extract (Zizyphus jujube)
Ginkgo biloba (Ginkgo biloba)
Suma extract (Pfaffia paniculata)
Mucuna pruriens extract (Cowhage)
Cinnamon (Cinnamomum zeylanicum)
Lycium berry extract (Lycium Barbarum) - also known as Goji Berry
Sarsaparila (Sarsaparilla Smilax)
Alpha Lipoic Acid free radical scavenger

Click Eyesight Rx to order this product or to order Lutein, Carotenoids, and other vision supporting supplements available at Physician Formulas
 

Genistein and Daidzen, Flavonoids, 1000 mg
Source Naturals
Genistein, a flavonoid derived from soybeans, has been the focus of scientific research since 1966. Studies have shown that genistein can bind to the same receptor sites as estrogen. Soybeans are the only significant dietary source of genistein; however, the amount of soy foods necessary to meet the body's needs can be difficult to incorporate into today's diet. In Asia, where soy is a staple, the daily intake can be up to 20 times that of a Western diet. Source Naturals Genistein is made from flavonoids -rich soybean powder that yields a consistent standardized isoflavone content. This unique chemical-free process requires approximately 400 pounds of soybeans to yield just one pound of finished product.

Flavonoids Supplement Facts:
Serving Size 2 Tablets
Serving Per Container 60

Amount Per Serving:
Isoflavone-rich - 2,000 mg*
Soybean Powder (Soylife™) Yielding:
   Daidzein - 34 mg
   Glycitein - 20 mg
   Genistein - 8 mg
   Total Isoflavones - 62 mg

Click here Flavonoids to order

Subscribe to a FREE Supplement Research Update newsletter. Twice a month we email a brief abstract of several studies on various supplements and natural medicine topics - including benefit of green tea and EGCG - and their practical interpretation by Ray Sahelian, M.D.

Suggested Use: One or two flavonoids tablets daily with a meal, or as recommended by your health care professional.
Flavonoids daily value not established.

The major subclasses of Flavonoids:
Flavonoids are a subclass of polyphenols. Flavonoids are widely distributed in nature, albeit not uniformly. As a result, specific groups of foods are often rich sources of one or more subclasses of these polyphenols. The polyphenolic structure of flavonoids and tannins renders them quite sensitive to oxidative enzymes and cooking conditions.
     Anthocyanins  and anthocyanidins are a large water-soluble pigment group found in a large number of fruits, vegetables and flowers. particularly grapes, pomegranate, and berries. These pigments give plants their brilliant colors ranging from pink through scarlet, purple and blue. Bilberry and other berries have a high concentration of anthocyanins. Scientists have identified more than 500 different anthocyanins. Cyanidin, pelargonidin. Anthocyanidin + sugar = Anthycyanin.
      Catechins or Flavanols are found found in tea and grape seeds. Cocoa can be a rich source of antioxidants including the flavan-3-ols, epicatechin and catechin, and their oligomers (procyanidins).
      Flavones -- Apigenin, Luteolin hispidulin. Luteolin is found in broccoli and greet chili. Apigenin is found in Chinese cabbage and bell pepper. Chrysin belongs to the flavone class of flavonoids.
      Flavonols --  are found at high concentrations in onions, apples, red wine, broccoli, tea, and Ginkgo biloba. The most common in the American diet are Quercetin (70%), Kaempferol (16%), and Myricetin (6%); fisetin. These flavonols are found in high amounts in kale, onions, hot peppers, and rutabagos. Quercetin is also found in Rose hips. Another flavonol, icariin, is found in horny goat weed.
      Flavanones -- Hesperidin, Naringen.
      Isoflavones -- Genistein, Daidzein are found in soy and in legumes. Kudzu also has isoflavones.

Potential Benefits of Flavonoids
Epidemiological evidence suggests an inverse relationship between dietary intake of flavonoids and cardiovascular risk. In other words, the higher the amount of flavonoids in the diet, the lower the risk for heart disease. The biological activities of flavonoids are partly related to their antioxidative effects.
   Accumulated evidence from experimental and epidemiological studies indicates that there is a low risk of degenerative diseases, cardiovascular disease, hypertension, cataract, stroke and, in particular, cancers in people with a high intake of fruit and vegetables. This protective effect is assumed to be associated mainly with the antioxidant activities of either individual or interacting bioactive components present in the fruits and vegetables, and with other biochemical and physical characteristics of the identified and unknown bioactive components. The implicated bioactive components present in citrus fruits include vitamin C, beta-carotene, flavonoids, limonoids, folic acid, and dietary fiber. A high intake of citrus fruits may reduce the risk of degenerative diseases.

Potential uses of Flavonoids

Anti-inflammatory
Most flavonoids have anti-inflammatory properties. Hence the use of flavonoids may be appropriate in some medical conditions involved in inflammation.

Flavonoids and the Immune system
Most flavonoids have anti-germ activity, including bacteria and viruses.

Flavonoids and Cancer
Most flavonoids have anti-tumor properties.

Flavonoids as Anti-oxidants
Flavonoids are powerful antioxidants. Extracts from onion and various flavonoids induce the cellular antioxidant system. Onion extract and quercetin were able to increase the intracellular concentration of glutathione by approximately 50%.

Vasodilation and nitric oxide production
Diets rich in either flavonoids including red wine, quercetin or catechin induce endothelium-dependent vasorelaxation. This means that blood vessels are more dilated and this may be beneficial in vascular diseases such as claudication or coronary or heart disease.

Flavonoids for brain health
If your diet has plenty of flavonoids, you are likely helping maintain a healthy brain in old age and lower your risk for heart disease. Flavonoids are potent antioxidants found in plant-based foods from red wine to tea to vegetables. Dr. Luc Letenneur of INSERM in Bordeaux, France, followed a group of 1,640 older, dementia-free individuals for 10 years, recording information on their diet at the beginning of the study. The men and women who took in the most flavonoids showed significantly better mental performance at the beginning of the study, even after the researchers adjusted the data for the influence of sex, level of education, and age. And those who ranked in the top half for flavonoid consumption showed more favorable progress in their cognitive function over time; for example, after 10 years, men and women in the lowest fourth for flavonoid consumption had lost 2.1 points on a test of cognitive function known as the Mini-Mental State Examination, compared to a 1.2-point loss for the people in the highest fourth for flavonoid intake. American Journal of Epidemiology, June 15, 2007.

Flavonoids and Herpes Virus
Antiherpetic activities of flavonoids against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in vitro.
Arch Pharm Res. 2005 Nov;28(11):1293-301. Immune Modulation Research Group, The School of Pharmacy, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
Flavonoids, a group of low molecular weight phenylbenzopyrones, have various pharmacological properties including antioxidant, anticancer, bactericidal, and anti-inflammatory. We carried out anti-herpetic assays on 18 flavonoids in five classes and a virus -induced cytopathic effect (CPE) inhibitory assay, plaque reduction assay, and yield reduction assay were performed. When flavonoids were applied at various concentrations to Vero cells infected by Herpes simplex virus 1 and 2, most of the flavonoids showed inhibitory effects on virus-induced CPE. Among the flavonoids, EC, ECG (flavanols), genistein (isoflavone), naringenin (flavanone), and quercetin (flavonol) showed a high level of CPE inhibitory activity. The antiviral activity of flavonoids were also examined by a plaque reduction assay. EC, ECG, galangin, and kaempferol showed a strong antiviral activity, and catechin, EGC, EGCG, naringenin, chrysin, baicalin, fisetin, myricetin, quercetin, and genistein showed moderate inhibitory effects against HSV-1. In these experiments, flavanols and flavonols appeared to be more active than flavones. Furthermore, treatment of Vero cells with ECG and galangin (which previously showed strong antiviral activities) before virus adsorption led to a slight enhancement of inhibition as determined by a yield reduction assay, indicating that an intracellular effect may also be involved.

Chemistry of Flavonoids
Flavonoids are a subclass of polyphenols. They generally consist of two aromatic rings, each containing at least one hydroxyl, which are connected through a three-carbon "bridge" and become part of a six-member heterocyclic ring. The flavonoids are further divided into subclasses based on the connection of an aromatic ring to the heterocyclic ring, as well as the oxidation state and functional groups of the heterocyclic ring. Within each subclass, individual compounds are characterized by specific hydroxylation and conjugation patterns. Many flavonoids in foods also occur as large molecules (tannins). These include condensed tannins (proanthocyanidins), derived tannins and hydrolysable tannins. For proanthocyanidins, three subclasses (15 characterized) have been identified in foods. Monomers are connected through specific carbon-carbon and ether linkages to form polymers. Derived tannins are formed during food handling and processing, and found primarily in black and oolong teas. Flavonoids are widely distributed in nature, albeit not uniformly. As a result, specific groups of foods are often rich sources of one or more subclasses of these polyphenols. The polyphenolic structure of flavonoids and tannins renders them quite sensitive to oxidative enzymes and cooking conditions. Scientists in several countries have estimated intakes of a few subclasses of flavonoids from limited food composition databases. These observations suggest large differences in consumption, due in part to cultural and food preferences among populations of each country.

Food Content of Flavonoids
Studies were conducted on the flavonoids (myricetin, quercetin, kaempferol, luteolin, and apigenin) contents of 62 edible tropical plants. The highest total flavonoids content was in onion leaves (1497 mg/kg quercetin, 391 mg/kg luteolin, and 832 mg/kg kaempferol), followed by Semambu leaves (2041.0 mg/kg), bird chili (1663.0 mg/kg), black tea (1491.0 mg/kg), papaya shoots (1264 mg/kg), and guava (1128 mg/kg). The major flavonoid in these plant extracts is quercetin, followed by myricetin and kaempferol. Luteolin could be detected only in broccoli (74 mg/kg dry weight), green chili (33.0 mg/kg), bird chili (1035.0 mg/kg), onion leaves (391.0 mg/kg), belimbi fruit (202.0 mg/kg), belimbi leaves (464.5 mg/kg), French bean (11.0 mg/kg), carrot (37.5 mg/kg), white radish (9.0 mg/kg), local celery (80.5 mg/kg), limau purut leaves (30.5 mg/kg), and dried asam gelugur (107.5 mg/kg). Apigenin was found only in Chinese cabbage (187.0 mg/kg), bell pepper (272.0 mg/kg), garlic (217.0 mg/kg), belimbi fruit (458.0 mg/kg), French peas (176.0 mg/kg), snake gourd (42.4 mg/kg), guava (579.0 mg/kg), wolfberry leaves (547.0 mg/kg), local celery (338.5 mg/kg), daun turi (39.5 mg/kg), and kadok (34.5 mg/kg). In vegetables, quercetin glycosides predominate, but glycosides of kaempferol, luteolin, and apigenin are also present. Fruits contain almost exclusively quercetin glycosides, whereas kaempferol and myricetin glycosides are found only in trace quantities.

Dr. Sahelian's thoughts on Flavonoids
Flavonoids have been studied for several decades. At this time I believe enough research on Flavonoids has been accumulated to begin taking advantage of these fascinating compounds in clinical use. A number of medical conditions could be prevented or improved with the use of Flavonoids. These include circulatory disorders such as hypertension and coronary artery disease,, lung disorders such as asthma, cancers of various types, inflammatory conditions, certain liver conditions, diabetes, mood disorders, eye disorders such as cataracts, weak eyesight due to aging, and macular degeneration. We should consider flavonoids as compounds necessary for the various organs and tissues, and part of the countless substances necessary for proper functioning of this amazing organism we call the human body.

Flavonoid Research Update
Flavonoids inhibit platelet function through binding to the thromboxane A2 receptor.
J Thromb Haemost. 2005 Feb;3(2):369-76.
Dietary flavonoids are known for their antiplatelet activity resulting in cardiovascular protection, although the specific mechanisms by which this inhibition occurs has not been fully established. The aim of this study was to investigate the interaction of nine flavonoids representative of various chemical classes, with platelet responses dependent on thromboxane A(2) (TxA(2)) generation and on receptor antagonism, and to analyze the structural requirements for such effects. METHODS: The effect of several types of flavonoids on platelet aggregation, serotonin release, and TxA(2) generation was investigated. RESULTS: Flavones (apigenin and luteolin) and isoflavones (genistein) abrogated arachidonic acid and collagen-induced platelet responses, such as aggregation and secretion, with a less substantial effect on TxA(2) synthesis. Tight binding of flavonoids to the human TxA(2) receptor relies on structural features such as the presence of the double bond in C2-C3, and a keto group in C4. CONCLUSIONS: The inhibition by specific flavonoids of in vitro platelet responses induced by collagen or arachidonic acid seems to be related, to a great extent, to their ability to compete for binding to the TxA(2) receptor. Therefore, antagonism of this TxA(2) receptor may represent an additional mechanism for the inhibitory effect of flavonoids in platelet function.

Review: dietary flavonoids and cancer risk: evidence from human population studies.
Nutr Cancer. 2004;50(1):1-7. Neuhouser ML.
High dietary intake of fruits and vegetables is consistently associated with a reduced risk of common human cancers, including cancers of the lung, breast, prostate, and colon. It is unknown which bioactive compound or compounds in plant foods provide the chemoprotective effects. One class of compounds currently under investigation is flavonoids, a large group of compounds with similar structure, consisting of two phenolic benzene rings linked to a heterocyclic pyran or pyrone. Although there are numerous in vitro and animal model data suggesting that flavonoids influence important cellular and molecular mechanisms related to carcinogenesis, such as cell cycle control and apoptosis, there are limited data from human population studies. This article reviews data from four cohort studies and six case-control studies, which have examined associations of flavonoid intake with cancer risk. There is consistent evidence from these studies that flavonoids, especially quercetin, may reduce the risk of lung cancer. Further research using new dietary databases for food flavonoid content is needed to confirm these findings before specific public health recommendations about flavonoids can be formulated.

Vasorelaxing effects of flavonoids: investigation on the possible involvement of potassium channels.
Naunyn Schmiedebergs Arch Pharmacol. 2004 Oct;370(4):290-8.
A flavonoid-rich diet has been associated with a lower incidence of cardiovascular diseases, probably because of the antioxidant and vasoactive properties of flavonoids. Indeed, many flavonoids show vasorelaxing properties, due to different and often not yet completely clarified mechanisms of action. Among them, the activation of vascular potassium channels has been indicated as a possible pathway, accounting, at least in part, for the vasodilatory action of some flavonoid derivatives, such as apigenin and dioclein. Therefore, this work aims at evaluating, on in vitro isolated rat aortic rings, the endothelium-independent vasorelaxing effects of a number of flavonoid derivatives, to identify a possible activation of calcium-activated and/or ATP-sensitive potassium channels and to indicate some possible structure-activity relationships. Among the several flavonoids submitted to the pharmacological assay, only baicalein and quercetagetin were almost completely ineffective, while quercetin, hesperidin, quercitrin and rhoifolin exhibited only a partial vasorelaxing effect. On the contrary, acacetin, apigenin, chrysin, hesperetin, luteolin, pinocembrin, 4'-hydroxyflavanone, 5-hydroxyflavone, 5-methoxyflavone, 6-hydroxyflavanone and 7-hydroxyflavone, belonging to the chemical classes of flavones and flavanones, showed full vasorelaxing effects. The vasodilatory activity of hesperetin, luteolin, 5-hydroxyflavone and 7-hydroxyflavone were antagonised by tetraethylammonium chloride, indicating the possible involvement of calcium-activated potassium channels. Moreover, iberiotoxin clearly antagonised the effects of 5-hydroxyflavone, indicating the probable importance of a structural requirement (the hydroxy group in position 5) for a possible interaction with large-conductance, calcium-activated potassium channels. Finally, glibenclamide inhibited the vasorelaxing action of luteolin and 5-hydroxyflavone, suggesting that ATP-sensitive potassium channels may also be involved in their mechanism of action.

Licorice Flavonoids Suppress Abdominal Fat Accumulation and Increase in Blood Glucose Level in Obese Diabetic KK-A(y) Mice.
Biol Pharm Bull. 2004 Nov;27(11):1775-8.
Licorice, the root of the Glycyrrhiza species, is one of the most frequently employed botanicals in traditional medicines. In this study, we investigated the effects of hydrophobic flavonoids from Glycyrrhiza glabra LINNE on abdominal fat accumulation and blood glucose level in obese diabetic mice. These results indicate that licorice hydrophobic flavonoids have abdominal fat-lowering and hypoglycemic effects, possibly mediated via activation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma).

The flavones luteolin and apigenin inhibit in vitro antigen-specific proliferation and interferon-gamma production by murine and human autoimmune T cells.
Biochem Pharmacol. 2004 Aug 15;68(4):621-9.
Plant-derived flavonoids are inhibitors of various intracellular processes, notably phosphorylation pathways, and potential inhibitors of cellular autoimmunity. In this study, the inhibiting effects of various flavonoids on antigen-specific proliferation and interferon-gamma (IFN-gamma) production by human and murine autoreactive T cells were evaluated in vitro. T-cell responses were evaluated for the human autoantigen alpha B-crystallin, a candidate autoantigen in multiple sclerosis, and for the murine encephalitogen proteolipid protein peptide PLP (139-151). The flavones apigenin and luteolin were found to be strong inhibitors of both murine and human T-cell responses while fisitin, quercitin, morin and hesperitin, members of the subclasses of flavonoles and flavanones, were ineffective. Antigen-specific IFN-gamma production was reduced more effectively by flavones than T-cell proliferation, suggesting that the intracellular pathway for IFN-gamma production in T cells is particularly sensitive to flavone inhibition. These results indicate that flavones but not flavanoles or flavanones are effective inhibitors of the potentially pathogenic function of autoreactive T cells. The effects of flavones were the same for human and murine autoreactive T cells, stressing the usefulness of animal models of autoimmunity for further studies on the effects of flavonones on autoimmune diseases.

[Flavonoids: risks or therapeutic opportunities?]
Recenti Prog Med. 2004 Jul-Aug;95(7-8):345-51.
Flavonoids are polyphenolic compounds that occur ubiquitously in fruits and vegetables. Over 4,000 different flavonoids have been described, and they are categorized into flavonols, flavones, catechins, flavanones, anthocyanidins and isoflavonoids. Flavonoids have many different biological effects in numerous mammalian cell systems, showed both in vitro and in vivo. Recently, much attention has been paid to their antioxidant properties and to their inhibitory role in various stages of tumour development in animal studies. In epidemiological studies the intake of flavonoids was inversely associated with subsequent coronary heart disease and cancer. Soy, St. John's Wort, Silybum marianum, Ginkgo biloba, Citrus species, Vaccinum mirtillus, Hawthorn and tea are medicinal plants containing flavonoids whose efficacy in the treatment of a variety of diseases has been demonstrated in numerous clinical studies. The main question that has not been answered satisfactorily deal with the triad absorption/metabolism/efficacy of flavonoids and is actually an important unsolved problem in judging their many alleged health effects. The aim of this review is based on providing by means of experimental and clinical studies information about efficacy and toxicity of flavonoids, especially focusing on infantile leukaemia for which there has been an international warning without sufficient and affordable scientific data.

Antioxidant properties of raw and processed cabbages.
Int J Food Sci Nutr. 2004 May;55(3):191-9.
To study the effect of polyphenolics on antioxidant activities of cabbages, the amounts of total phenolics, total flavonoids, antioxidant capacity and individual phenolic compounds in raw and processed cabbages were determined. Fresh and pickled red cabbages exhibited the highest total phenolic contents (393.1+/-10.8 mg and 366.3+/-3.6 mg gallic acid equivalents/100 g fresh sample, respectively). Fresh and pickled red cabbages were also highest in flavonoids (108.1+/-9.3 mg and 72.4+/-4.4 mg catechin equivalents/100 g fresh sample, respectively). The antioxidant capacity (expressed as vitamin C equivalent antioxidant capacity) ranged from 57.1 to 695.6 mg vitamin C equivalents/100 g fresh sample, where raw and pickled red cabbages exhibited the highest antioxidant capacity. There was a good linear relationship between the total phenolics and antioxidant capacity (r2=0.9743), and between the total flavonoids and antioxidant capacity (r2=0.9557); however, the relationship between the ascorbic acid content and antioxidant capacity was very low (r2=0.1442). The antioxidant capacity of raw and processed cabbages was highly correlated with their contents of polyphenolics. Kaempferol, quercetin, and apigenin were the major flavonoids existing in cabbages except for raw and pickled red cabbages, where cyanidin was the predominant flavonoid (73.6-117.7 mg/kg). In the red cabbages, cyanidin was the major contributor to the antioxidant capacity as well as the content of total phenolics and flavonoids.

Vasorelaxing effects of flavonoids: investigation on the possible involvement of potassium channels.
Naunyn Schmiedebergs Arch Pharmacol. 2004 Oct;370(4):290-8.
A flavonoid-rich diet has been associated with a lower incidence of cardiovascular diseases, probably because of the antioxidant and vasoactive properties of flavonoids. Indeed, many flavonoids show vasorelaxing properties, due to different and often not yet completely clarified mechanisms of action. Among them, the activation of vascular potassium channels has been indicated as a possible pathway, accounting, at least in part, for the vasodilatory action of some flavonoid derivatives, such as apigenin and dioclein. Therefore, this work aims at evaluating, on in vitro isolated rat aortic rings, the endothelium-independent vasorelaxing effects of a number of flavonoid derivatives, to identify a possible activation of calcium-activated and/or ATP-sensitive potassium channels and to indicate some possible structure-activity relationships. Among the several flavonoids submitted to the pharmacological assay, only baicalein and quercetagetin were almost completely ineffective, while quercetin, hesperidin, quercitrin and rhoifolin exhibited only a partial vasorelaxing effect. On the contrary, acacetin, apigenin, chrysin, hesperetin, luteolin, pinocembrin, 4'-hydroxyflavanone, 5-hydroxyflavone, 5-methoxyflavone, 6-hydroxyflavanone and 7-hydroxyflavone, belonging to the chemical classes of flavones and flavanones, showed full vasorelaxing effects. The vasodilatory activity of hesperetin, luteolin, 5-hydroxyflavone and 7-hydroxyflavone were antagonised by tetraethylammonium chloride, indicating the possible involvement of calcium-activated potassium channels. Moreover, iberiotoxin clearly antagonised the effects of 5-hydroxyflavone, indicating the probable importance of a structural requirement (the hydroxy group in position 5) for a possible interaction with large-conductance, calcium-activated potassium channels. Finally, glibenclamide inhibited the vasorelaxing action of luteolin and 5-hydroxyflavone, suggesting that ATP-sensitive potassium channels may also be involved in their mechanism of action.

Flavonoids such as luteolin, fisetin and apigenin are inhibitors of interleukin-4 and interleukin-13 production by activated human basophils.
Int Arch Allergy Immunol. 2004 Jun;134(2):135-40.
BACKGROUND: We have previously shown that fisetin, a flavonol, inhibits IL-4 and IL-13 synthesis by allergen- or anti-IgE-antibody-stimulated basophils. This time, we investigated the inhibition of IL-4 and IL-13 production by basophils by other flavonoids and attempted to determine the fundamental structure of flavonoids related to inhibition. We additionally investigated whether flavonoids suppress leukotriene C4 synthesis by basophils and IL-4 synthesis by T cells in response to anti-CD3 antibody. METHODS: Highly purified peripheral basophils were stimulated for 12 h with anti-IgE antibody alone or anti-IgE antibody plus IL-3 in the presence of various concentrations of 18 different kinds of flavones and flavonols. IL-4 and IL-13 concentrations in the supernatants were then measured. Leukotriene C4 synthesis was also measured after basophils were stimulated for 1 h in the presence of flavonoids. Regarding the inhibitory activity of flavonoids on IL-4 synthesis by T cells, peripheral blood mononuclear cells were cultured with flavonoids in anti-CD3-antibody-bound plates for 2 days. RESULTS: Luteolin, fisetin and apigenin were found to be the strongest inhibitors of both IL-4 and IL-13 production by basophils but did not affect leukotriene C4 synthesis. At higher concentrations, these flavonoids suppressed IL-4 production by T cells. Based on a hierarchy of inhibitory activity, the basic structure for IL-4 inhibition by basophils was determined. CONCLUSIONS: Due to the inhibitory activity of flavonoids on IL-4 and IL-13 synthesis, it can be expected that the intake of flavonoids, depending on the quantity and quality, may ameliorate allergic symptoms or prevent the onset of allergic diseases.

Effects of flavonoids on the resistance of microsomes to lipid peroxidation in vitro and ex vivo.
Bull Exp Biol Med. 2003 Dec;136(6):572-5.
Incubation of rat liver microsomes with preparations of grape flavonoids, dihydroquercetin, and silibinin increased their resistance to lipid peroxidation induced by NADPH-Fe2+. This was manifested in less pronounced accumulation of lipid peroxidation products and changes in activity of microsomal enzymes induced by lipid peroxidation. In vitro antioxidant activity of grape flavonoids markedly surpassed that of dihydroquercetin and silibinin. Addition of flavonoids into fodder led to moderate, statistically significant, and similar increase in the resistance of rat liver microsomes to ex vivo induced lipid peroxidation.

Pharmacokinetics and metabolism of dietary flavonoids in humans.
Free Radic Res. 2004 Aug;38(8):771-85.
Flavonoids are components of fruit and vegetables that may be beneficial in the prevention of disease such as cancer and cardiovascular diseases. Their beneficial effects will be dependent upon their uptake and disposition in tissues and cells. The metabolism and pharmacokinetics of flavonoids has been an area of active research in the last decade. To date, approximately 100 studies have reported the pharmacokinetics of individual flavonoids in healthy volunteers. The data indicate considerable differences among the different types of dietary flavonoids so that the most abundant flavonoids in the diet do not necessarily produce the highest concentration of flavonoids or their metabolites in vivo. Small intestinal absorption ranges from 0 to 60% of the dose and elimination half-lives (T1/2) range from 2 to 28h. Absorbed flavonoids undergo extensive first-pass Phase II metabolism in the small intestine epithelial cells and in the liver. Metabolites conjugated with methyl, glucuronate and sulfate groups are the predominant forms present in plasma. This review summarizes the key differences in absorption, metabolism and pharmacokinetics between the major flavonoids present in the diet. For each flavonoid, the specific metabolites that have been identified so far in vivo are indicated. These data should be considered in the design and interpretation of studies investigating the mechanisms and potential health effects of flavonoids.

Comprehensive study on vitamin C equivalent antioxidant capacity (VCEAC) of various polyphenolics in scavenging a free radical and its structural relationship.
Crit Rev Food Sci Nutr. 2004;44(4):253-73.
Department of Food Science and Technology, Cornell University, Geneva, New York
Antioxidant capacity for a wide range of natural or synthetic polyphenolics was comprehensively evaluated by vitamin C equivalent antioxidant capacity (VCEAC) assay using free blue/green ABTS radicals. The polyphenolics tested are grouped into the following categories: vitamins (beta-carotene, alpha-tocopherol, vitamin A, and vitamin C), phenolic acids (benzoic acid, phenylacetic acid, cinnamic acid, and their derivatives), flavonoids (anthocyanidin, flavanol, chalcone, flavanone, flavone, flavonol, isoflavone, and their derivatives), synthetic food additives (BHA, BHT, TBHQ, and PG), and other miscellaneous polyphenolics (ellagic acid, sesamol, eugenol, thymol, etc.). A positive linear relationship between VCEAC and the number of free OH groups around the flavonoid framework was found, whereas, for phenolic acids, the linear relationship was not as good as with the flavonoid aglycones. Groups of chemicals having comparable structures generally showed similar trends. Polyphenolics commonly showed a higher VCEAC compared to monophenolics. Compounds like gallic acid with 3 vicinal hydroxy substitutions on the aromatic ring in phenolic acids or like epigallocatechin with 3 vicinal hydroxy substitutions on the B ring in flavonoids showed the highest antioxidant capcity among the groups. In the flavonoids, 2 characteristic chemical structures were very important, the catechol moiety in the B ring and the 3-OH functional group in a chroman ring. Glycosylated flavonoids showed less potent antioxidant capacity than their aglycone alone. Synthetic antioxidant food additives (BHA, TBHQ, and BHT) conventionally used in the food industry were less effective antioxidants than ascorbic acid. Other naturally occurring polyphenolics tested followed the expected general trends of phenolic acids and flavonoids.

Flavonoids of St. John's Wort Reduce HPA Axis Function in the Rat.
Planta Med. 2004 Oct;70(10):1008-11.
A common biological alteration in patients with major depression is the activation of the hypothalamic-pituitary-adrenal (HPA) axis, manifested as hypersecretion of adrenocorticotropic hormone (ACTH) and cortisol. The hyperactivity of the HPA axis in depressed patients can be corrected during clinically effective therapy with standard antidepressant drugs such as imipramine, indicating that the HPA axis may be an important target for antidepressant action. We previously showed that a methanolic extract of St. John's wort (St. John's wort) and hypericin, one of its active constituents, both have delayed effects on the expression of genes that are involved in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis , whereas the phloroglucinol derivative hyperforin was inactive in the same model . Since flavonoids of St. John's wort are also discussed as active constituents it was of interest to determine whether these compounds can modulate HPA axis function. Imipramine (15 mg/kg), hypericin (0.2 mg/kg), hyperoside (0.6 mg/kg), isoquercitrin (0.6 mg/kg) and miquelianin (0.6 mg/kg) given daily by gavage for two weeks significantly down-regulated circulating plasma levels of ACTH and corticosterone by 40 - 70 %. However, none of the compounds tested had an effect on plasma ACTH and corticosterone levels after chronic treatment (daily gavage for 8 weeks). Our data suggest that besides hypericin, flavonoids of St. John's wort play an important role in the modulation of HPA axis function. Furthermore, the results support the hypothesis that flavonoids are involved in the antidepressant effects of St. John's wort.

Vasorelaxing effects of flavonoids: investigation on the possible involvement of potassium channels.
Naunyn Schmiedebergs Arch Pharmacol. 2004 Sep 17
A flavonoid-rich diet has been associated with a lower incidence of cardiovascular diseases, probably because of the antioxidant and vasoactive properties of flavonoids. Indeed, many flavonoids show vasorelaxing properties, due to different and often not yet completely clarified mechanisms of action. Among them, the activation of vascular potassium channels has been indicated as a possible pathway, accounting, at least in part, for the vasodilatory action of some flavonoid derivatives, such as apigenin and dioclein. Therefore, this work aims at evaluating, on in vitro isolated rat aortic rings, the endothelium-independent vasorelaxing effects of a number of flavonoid derivatives, to identify a possible activation of calcium-activated and/or ATP-sensitive potassium channels and to indicate some possible structure-activity relationships. Among the several flavonoids submitted to the pharmacological assay, only baicalein and quercetagetin were almost completely ineffective, while quercetin, hesperidin, quercitrin and rhoifolin exhibited only a partial vasorelaxing effect. On the contrary, acacetin, apigenin, chrysin, hesperetin, luteolin, pinocembrin, 4'-hydroxyflavanone, 5-hydroxyflavone, 5-methoxyflavone, 6-hydroxyflavanone and 7-hydroxyflavone, belonging to the chemical classes of flavones and flavanones, showed full vasorelaxing effects. The vasodilatory activity of hesperetin, luteolin, 5-hydroxyflavone and 7-hydroxyflavone were antagonised by tetraethylammonium chloride, indicating the possible involvement of calcium-activated potassium channels. Moreover, iberiotoxin clearly antagonised the effects of 5-hydroxyflavone, indicating the probable importance of a structural requirement (the hydroxy group in position 5) for a possible interaction with large-conductance, calcium-activated potassium channels. Finally, glibenclamide inhibited the vasorelaxing action of luteolin and 5-hydroxyflavone, suggesting that ATP-sensitive potassium channels may also be involved in their mechanism of action.

Eating dark chocolate, or taking a cocoa supplement, which have plenty of flavonoids, improves healthy blood flow. Chocolate improves the function of blood vessels, allowing them to dilate, thereby preventing the formation of potentially damaging clots.

The intake of 400-600 g/d of fruits and vegetables is associated with reduced incidence of many common forms of cancer, and diets rich in plant foods are also associated with a reduced risk of heart disease and many chronic diseases of ageing. These foods contain phytochemicals that have anti-cancer and anti-inflammatory properties which confer many health benefits. Many phytochemicals are colourful, and recommending a wide array of colourful fruits and vegetables is an easy way to communicate increased diversity of intake to the consumer. For example, red foods contain lycopene, the pigment in tomatoes, which is localized in the prostate gland and may be involved in maintaining prostate health, and which has also been linked with a decreased risk of cardiovascular disease. Green foods, including broccoli, Brussels sprouts and kale, contain glucosinolates which have also been associated with a decreased risk of cancer. Garlic and other white-green foods in the onion family contain allyl sulphides which may inhibit cancer cell growth. Other bioactive substances in green tea and soybeans have health benefits as well.

Several flavonoids (e.g. chrysin, apigenin) and other phytoconstituents possess aromatase-inhibiting properties.

Additional herbs with high content of Flavonoids
Oroxylum Indicum

Flavononoid email
Q. Can flavonoid supplements help with Raynauds phenomenon?
     A. I am not sure, but it is worth a try since flavonoids help dilate blood vessels.

Sometimes people make the mistake of spelling flavonoids as flavanoids