Bioflavonoids: Natural Relief for Allergies and Asthma


Jennifer Mueller, M.S. Candidate

Summer is here, and with it, hundreds of flowering plants releasing clouds of pollen into the air. For anyone with allergies, this is the worst time of year. Medications are available, but they either put you in a daze, or are extremely expensive. Allergy sufferers wonder: isn't there anything that will help? The answer is a resounding yes although the source may not be what you expect.
The next time you browse through the produce department in your local supermarket, take a closer look at some of those fruits and vegetables. They contain substances called bioflavonoids, which are part of a larger group of molecules called polyphenols. These flavonoids play a major role in the color and taste of many of the fruits and vegetables we eat, and they possess numerous medical benefits as well.

History
Interest in the biological function of flavonoids was first expressed in 1936 by Szent-Gyorgi, et al, who reported that flavonoids alleviated some of the symptoms of scurvy.(1) At this time, these compounds were designated as vitamin P. However, further studies in the next few decades showed conflicting and inconclusive results when compared to Szent-Gyorgis research. Consequently, interest died until only recently.
 

Within the last few decades, extensive studies have been conducted on a wide range of flavonoids, finding a variety of beneficial effects. Anthocyanidins (found in red wine and pomegranates) have demonstrated anti-cancer, anti-inflammatory, and anti-microbial effects.(2,3) Gallates and catechins (found in green teas) have shown anti-cancer effects as well.(4) Quercetin, rutin and others have shown strong protective effects against lipid peroxidation,(2) and quercetin has also been proven effective in the prevention and treatment of diabetes-induced cataracts.(5) Silymarin (found in milk thistle) is used in Europe as a prescription drug to treat various liver diseases, and cyanadin and catechins have also shown similar hepatoprotective effects.(2,3) Numerous flavonoids have demonstrated potent anti-microbial and anti-viral effects, and some, such as quercetin and morin, were effective in lowering cholesterol in the blood.(6) While numerous beneficial effects of flavonoids have been examined, perhaps one of the best documented medical applications is their anti-allergic effects.

Allergies and Flavonoids
An allergic reaction is caused by a rapid release of histamine from mast cells (immune cells). Following a stimulus by an allergen whether the mode of contact is inhalation, touch, or ingestion the enzyme calcium ATP-ase is activated. This pumps calcium into the cells, stimulating the release of histamine, which travels throughout the body and starts the chain of events which eventually leads to the familiar symptoms of allergy: nasal discharge, stinging and watery eyes, itching, and hives. There are numerous medications available, both by prescription and over the counter, to give relief to the allergy sufferer. However, most, if not all, produce unpleasant side effects such as dry mouth, nausea, and drowsiness.(7) These medications work by blocking the histamine receptors on other cells, not by blocking the initial release of the histamine itself. Asthma is caused by a similar pathway to allergy. The asthma trigger stimulates the immune cells to induce the production of prostaglandins and leukotrienes and the release of histamines. However, in asthma, the ratio of leukotrienes to prostaglandins is more important in the progression of the symptoms than the release of histamine.(9)
 
Bioflavonoids have long been known to possess anti-allergic effects. As early as the 1950s, studies showed that flavonoids could prevent the release of histamines and inhibit anaphylaxis.(8) It wasnt until some years later, however, that any more attention was paid to the link between flavonoids and allergy. The breakthrough was the discovery of the flavonoid khellin that turned out to be an effective muscle relaxant. During attempts to improve its muscle-relaxing capabilities, a series of derivatives was synthesized. One of these derivatives was disodium cromoglycate, Cromolyn. Studies suggest that Cromolyn could alleviate the symptoms of asthma and reduce the need for other asthma medications when taken over long periods of time. It acts by decreasing the transport of calcium into the cells, thus slowing the release of histamine.(10) Preliminary studies suggest that Cromolyn is effective in reducing the symptoms of allergy, both when taken via inhalation and when applied topically in the eyes.(10)
Other derivatives of khellin have also been shown to be effective against asthma and allergy. The experimental bioflavonoid-derivative drugs FPL 52757 and FPL 57787 were given orally to rats who were then exposed to an allergen. Both substances showed protection (similar to that seen with Cromolyn) against symptoms to the chemically-induced allergic reaction.(11) FPL 55712 given via aerosol reduced asthmatic symptoms in guinea pigs,(12) and FPL 52694 given orally to rats inhibited reactions to allergens injected under the skin. The mode of action for all these experimental bioflavonoid derivatives appears similar to Cromolyn inhibition of histamine release.(13)

Natural vs. Synthetic
While Cromolyn and the FPL series are all synthetically derived compounds, natural flavonoids have also shown anti-allergy and anti-asthmatic activity. One of the earliest studies examined varying levels of the bioflavonoid rutin combined with an antihistamine drug, in human subjects. Seventy-five percent of the subjects reported greater relief from allergy symptoms (sneezing, itching and tearing of eyes) when given the combination of flavonoid and drug than when given the drug alone.(7) In a later study, baicalin (a flavonoid used in ancient Chinese medicine to treat allergy and inflammation) was given orally to guinea pigs. After flavonoid treatment, asthma was chemically induced. The animals pretreated with the flavonoid showed a greater suppression of symptoms (histamine release and bronchoconstriction) than those that were untreated.(14)
In vitro studies (done in cell cultures instead of whole animals) have been conducted to determine the exact mode of action by which flavonoids suppress the symptoms of allergy and asthma. As mentioned earlier, the symptoms are caused by the release of histamine, leukotrienes, and prostaglandins from the immune cells. In one study, mast cells were treated with eleven different flavonoids, including quercetin and catechins. Histamine release was chemically induced. All the flavonoids tested exhibited some level of protective effect against the release of histamine by preventing the uptake of calcium into the cells.(15) Similar results have been shown in basophils treated with quercetin, which is chemically similar to the synthetically derived Cromolyn. Quercetin was quite effective at inhibiting the release of histamine from these cells, even at low doses.(16) It is interesting to note that in these and other studies, quercetin has been proven more effective at blocking histamine release than the synthetically derived Cromolyn.(4) While the exact mechanism by which flavonoids prevent calcium influx into the cells is still debated, it is thought that flavonoids may inhibit the enzyme cyclic AMP phosphodiesterase. This results in raised levels of cyclic AMP inside the mast cells, preventing the release of the histamine.(17,18)

Other Benefits
Flavonoids exert their protective effects in other ways as well. They inhibit lipoxygenase--the compound which stimulates the biosynthesis of leukotrienes, which play an important role in hypersensitivity to allergens, as well as www.ion of asthmatic symptoms.(18,19) Certain flavonoids also inhibit arachidonic acid peroxidation as well. Arachidonic acid is a precursor of prostaglandins, compounds involved in inflammation and allergic responses. Catechins were some of the most potent inhibitors of prostaglandin synthesis.(19)
As can be seen, bioflavonoids are highly effective anti-allergy and anti-asthma agents. While more research is needed to determine exact doses, the best methods of delivery (oral versus inhaled), and which combinations of flavonoids can offer the best effects, it is clear that bioflavonoids offer allergy sufferers a new form of relief, without the annoying side effects of prescription drugs. When taking into account all the other ways they can act as anti-inflammatories, anti-viral and anti-microbial agents, and even anti-cancer agents, it is clear that bioflavonoids offer a wide range of possibilities for the future of medicine.

Jennifer Mueller is a Masters Candidate in Nutrition Science at the University of California at Davis. Her primary focus is developmental nutrition and prenatal health. She was Managing Editor for the Journal of Optimal Nutrition and has studied under Dr. Brian Liebovitz, the noted medical nutritionist.

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References:
1. Szent-Gyorgyi A, Rusznyak S. Vitamin P: Flavonoids as vitamins. Nature 138: 27, 1936.

2. Cody V, Middleton E Jr, Harbone J (editors). Plant Flavonoids in Biology and Medicine, vol 1. Alar R. Liss, Inc. New York, NY 1986.

3. Cody V, Middleton E Jr, Harbone J, Beretz A (editors). Plant Flavonoids in Biology and Medicine, vol 2. Alar R. Liss, Inc. New York, NY 1988.

4. Liebovitz B, Mueller J. Bioflavonoids and polyphenols: medical applications. J Opt Nutr 2(1): 17-35, 1993.

5. Varma S, Kinoshita J. Inhibition of lens aldose reductase by flavonoids: their possible role in the prvention of diabetic cataracts. Biochem Pharmacol 25: 2505-13, 1976.

6. Yugarani T, Tan B, Teh M et al. Effects of polyphenolic natural products on the lipid profiles of rats fed high fat diets. Lipids 27: 181-86, 1992.

7. Schoenkerman B, Justice R. Treatment of allergic disease with a combination of antihistamine and flavonoid. Annals of Allergy 10: 138-41, 1952.

8. Clark W, Mackay E. Effect of flavonoid substances on histamine toxicity, anaphylactic shock and histamine-enhanced capilary permeability to dye. J Allergy 21: 133-47, 1950.

9. Davies B, Moodley I. Antiallergic compounds. Pharmacol Therap 17: 279-97, 1982.

10. Bernstein I, Johnson C, Tse C. Therapy with Cromlyn sodium. Annals Internal Med 89: 228-233, 1978.

11. Augstein J, et al. New orally effective chromone derivatives for the threatment of asthma. Agents and Actions 7(4): 443-45, 1971.

12. ODonnell M, Welton A. Pharmacologic properties of FPL 55712 administered by aerosol. Agents and Actions 14(1): 43-48, 1984.

13. Wells E, et al. The anti-allergic effects of FPL 52694. Int Arch Allergy Appl Immun 76: 188-90, 1985.

14. Nagai H, Osuga K, Koda A. Inhibition of hypersensitivity reactions by soluble derivatives of baicelin. Japan J Pharmacol 25: 763-72, 1945.

15. Amallal M et al. Inhibition of mast cell histamine released by flavonoids and biflavonoids. Planta Medica 16-20, 1985.

16. Middleton E Jr, Drzeqiecki G, Krishnarao D. Quercetin: an inhibitor of antigen-induced human basophil histamine release. J Immunol 127(2): 546-50, 1981.

17. Beretz A, Anton R, Stoclet J. Flavonoid compounds are potent inhibiters of cyclic AMP phosphodiesterase. Experentia 34: 1054-55, 1978.

18. Middleton E Jr, Kandaswami C. Effects of flavonoids on immune and inflammatory cell functions. Biochem Pharmacol 43: 1167-79, 1992.

19. Baumann J, Bruchhausen F, Wurm G. Flavonoids and related compounds as inhibitors of arachadonic acid peroxidation. Prostaglandins 20(4): 627-39, 1980.
 

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