Comprehensive Guide to Quercetin

QuercetinDr. James Meschino DC, MS, ND
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General Features
Quercetin is a flavonoid that serves as the backbone for many other flavonoids in nature, including the citrus flavonoids rutin, quercitin, and hesperidin. These derivates differ from Quercetin in that they have sugar molecules attached to their Quercetin backbone. Experimental studies reveal that many medicinal plants owe much of their biological activity to their high Quercetin content.1
This water-soluble pigment has been shown to inhibit histamine release at therapeutic doses, making it an attractive agent in the management of some allergic conditions, such as hay fever. It also demonstrates impressive anti-inflammatory and antioxidant properties, and like some other flavonoids (e.g. genistein, diadzein), appears to possess phytoestrogen effects. Under experimental conditions, its phytoestrogen effects have been shown to inhibit the proliferation of human breast cancer cells in test tube experiments. In one human trial, Quercetin supplementation demonstrated improvement in prostatitis, with 67% of patients experiencing significant improvement in the Quercetin group compared to only 20% of patients reporting improvement in the placebo group. This benefit may be due to its phytoestrogen activity and/or its anti-inflammatory properties.
Experimental studies also reveal that Quercetin may help to prevent cataracts in diabetics, by inhibiting the enzyme that forms sorbitol (aldose reductase) in the lens of the eye.
Clinical Application and Mechanism of Action
1. Anti-Inflammatory
Quercetin inhibits the manufacture and release of histamine and other allergic/inflammatory mediators, which gives Quercetin supplementation application in a variety of inflammatory and allergic reactions (arthritis, joint inflammation, asthma, hay fever, lupus).4-12
2. Diabetic Cataracts
Quercetin inhibits the aldose reductase enzyme, which converts glucose into sorbitol. Sorbitol build up in the lens of the eye (secondary to diabetes and hyperglycemia) is involved in the development of cataracts.
Elevated sorbitol may also contribute to the development of diabetic neuropathy and retinopathy. Thus, Quercetin may be beneficial in diabetes management for a number of reasons.13,14 Animal studies reveal that Quercetin effectively delays the onset of cataracts in diabetic animals.14
3. Anti-Tumor
Many flavonoids inhibit tumor formation, but Quercetin has demonstrated a very consistent effect in this regard. Under experimental conditions, Quercetin demonstrates a significant antiproliferative effect in regards to squamous cell carcinoma, leukemia, and cancers of the breast, ovaries, colon, rectum and brain.15-18 It is thought that Quercetin down-regulates enzymes that control the rate of cellular division (i.e. protein kinase, DNA-topoisomerase, ornithine decarboxylase), in addition to its mild phytoestrogen effects.
Dosage
1. Anti-Inflammatory/Anti-Allergy: as a single agent; 200-400 mg, three times per day. Combinations of bromelain and Quercetin have been shown to potentiate or enhance each others anti-inflammatory activity.21 The amount of bromelain should be equal to the amount of Quercetin.1 Bromelain also enhances the absorption of Quercetin.1
2. Diabetes (neuropathy or cataract protection): consider 200-400 mg (three times per day).
Adverse Side Effects and Toxicity
Animal studies demonstrate that Quercetin is extremely non-toxic and non-carcinogenic.22,23,24 In rare cases, allergic reactions to Quercetin can occur in humans.
Drug-Nutrient Interactions
1. Estradiol (found in oral contraceptives and hormone replacement therapy)
Quercetin may slow down the detoxification of estradiol by liver enzymes. There are no human reports of Quercetin potentiating the effects of estradiol through this mechanism at this time.
2. Felodipine
Felodipine is a calcium channel blocker used in the treatment of congestive heart failure, hypertension and Raynaud’s Syndrome. Test tube studies indicate that Quercetin inhibits the enzyme in the liver that is responsible for the breakdown of felodipine. This may result in higher, more potentially dangerous levels of felodipine in the bloodstream, although no human reports of adverse effects have been reported to date.
References
1. Murray M. Encyclopedia of Nutritional Supplements. Rocklin, CA: Prima Publishing; 1996. p. 320-31.
2. Beyer-Meyers A, et al. Diminished sugar cataractogenesis by quercetin. Exp Eye Res 1979; 28(6): 709-16
3. Chaudry PS, et al. Inhibition of human lens aldose reductase by flavonoids, sulindac, and indomethacin. Biochem Pharmacol. 1983; 32: 1995-98
4. Havsteen B. Flavonoids, a class of natural products of high pharmacological potency. Biochem Pharmacol 1983;32:1141-8.
5. Middleton E. The flavonoids. Trends Pharmaceut Sci 1984;5:334-8.
6. Ferrandiz ML, Alcaraz MJ. Anti-inflammatory activity and inhibition of arachidonic acid metabolism by flavonoids. Agents Action 1991;32:283-7.
7. Middleton E, Drzewiedi G. Flavonoid inhibition of human basophil histamine release stimulated by various agents. Biochem Pharmacol 1984;33:3333-8.
8. Middleton E, Drzewieki G. Naturally occurring flavonoids and human basophil histamine release. Int Arch Allergy Appl Immunol 1985;77:155-7.
9. Amella M, Bronner C, Briancon F, Haag M, Anton R, Landry Y. Inhibition of mast cell histamine release by flavonoids and bioflavonoids. Planta Medica 1985;51:16-20.
10. Pearce F, Befus AD, Bienenstock J. Mucoal mast cells, III. Effect of quercetin and other flavonoids on antigen-induced histamine secretion from rat intestinal mast cells. J Allergy Clin Immunol 1984;73:819-23.
11. Busse WW, Kopp DE, Middleton E. Flavonoid modulation of human neutrophil function. J Allergy Clin Immunol 1984;73:801-9.
12. Yoshimoto T, Furukawa M, Yamamoto S, Horie T, WatanabeKohno S. Flavonoids: Potent inhibitors of arachidonate 5-lipoxygenase. Biochem Biophys Res Common 1983;116:612-8.
13. Chaundry PS, Cambera J, Juliana HR, Varma SD. Inhibition of human lens aldose reductase by flavonoids, sulindac and indomethacin. Biochem Pharmacol 1983;32:1995-8.
14. Varma SD, Muzuno A, Kinoshita JH. Diabetic cataracts and flavonoids. Science 1977;195:87-9.
15. Elangovan V, et al. Studies on the chemopreventative potential of some naturally-occurring biovlavonoids in 7,12-dimethylbenz(a)anthracene-induced carcinogens in mouse skin. J Clin Biochem Nutr 1994;17:153-60.
16. Verma AK, Johnson JA, Gould MN, Tanner MA. Inhibition of 7,12-dimenthylbenz(a)anthracene and N-nitrosomethyl urea induced rat mammary cancer by dietary flavonol quercetin. Cancer res 1988;48:5754-5758.
17. Stavric B. Quercetin in our diet: from potent mutagen to probable anticarcinogen. Clin Biochem 1994;27:245-8.
18. Larocca LM, Giustacchini M, Maggiano N, Ranelletti FO, Piantelli M, Alcini E et al. Growth-inhibitory effect of quercetin and presence of type II estrogen binding sites in primary human transitional cell carcinomas. J Urol 1994;152:1029-33.
19. Castillo MH, Perkins E, Campbell JH, et al. The effects of the bioflavonoid quercetin on squamous cell carcinoma of head and neck origin. Am J Surg 1989: 351-5
20. Kuo SM. Antiproliferative potency of structurally distinct dietary flavonoids on human colon cancer cells. Cancer Letter 1996;110:41-8.
21. Tarayre JP, Lauressergues H. Advantages of a combination of proteolytic enzymes, flavonoids and ascorbic acid in comparison with non-steroid anti-inflammatory agents. Arzneim Forsch 1077;27:1144-9.
22. Hirono I, Ueno I, Hosaka S, Takanashi H, Matsushima T, Sugimura T et al. Carcinogenicity examination of quercetin and rutin in ACI rats. Cancer Lett 1981;13:15–21.
23. Kato K, et al. Lack of promotive effect of quercetin on methlazoxy acetate carcinogenesis in rats. J Toxicol Sci 1984;9:319-25.
24. Kato K, et al. Absence of initiating activity by quercitin in the rate liver. Ecotoxicol Environ Safety 1985;10:63-9.
25. Healthnotes online. Healthnotes Inc, 2000