Quercetin Introduction

Quercetin is a naturally occurring compound that is part of a larger category of substances referred to as flavonoids. The chemical name for quercetin is 3,3’4’,5,7-pentahydroxy flavone. Flavonoids tend to be yellow in color and more frequently occur as glycosides (linked to a sugar moiety) in nature. Quercetin is the aglycone (the non-sugar part) portion of a number of flavonoids, including rutin, quercetrin, isoquercetrin and hyperoside. [1]

Quercetin may possess potent anticancer and anti-inflammatory activities. Anti-inflammatory activity is likely due to quercetin’s ability to inhibit lipoxygenase and leukotriene B4, both of which are part of the inflammatory cascade. [2] As well, it inhibits histamine release from mast cells which is the basis of allergic reactions. [3]

Additionally, quercetin has demonstrated the ability to prevent oxidative stress, and to inhibit NF-kappaB activation in an experimental model of portal hypertensive gastropathy. [4] It also has the ability to constrain IL-12 signaling and Th1 differentiation, which may indicate its potential as a therapeutic agent for multiple sclerosis and other Th1 cell-mediated autoimmune diseases. [5] Quercetin is a potent inhibitor of tyrosine kinase, an important enzyme in tumor development, as well.

Quercetin is found in a variety of foods and botanicals. Food sources high in quercetin include allium family vegetables, brassica family vegetables, and apples. Hypericum perforatum, Gingko biloba, Sanguinaria canadensis, and Camellia sinensis contain significant amounts of this flavonoid. [1] Black currants, lingonberries and bilberries are also considered good sources of bioavailable quercetin. [6] Interestingly, quercetin from rutin has been shown to be more bioavailable in women than in men. [7]

Quercetin has been studied for a range of health conditions. In the past, quercetin has been used for inflammatory and allergic type conditions due to its ability to inhibit mast cell release of histamine. Quercetin is currently employed for uses concerning disorders of the urinary tract, vascular problems, dysfunctions due to oxidative stress, and even cancer.

Quercetin was examined for interstitial cystitis in both men and women. Twenty-two subjects with chronic pelvic pain syndrome were given a preparation of Cysta-Q complex at a dose that would be equivalent to 500 milligrams (mg) of quercetin, twice daily for a period of 4 weeks. [8] The results showed that in all parameters tested, quercetin demonstrated significant improvements without adverse reactions. The authors call for a large scale, randomized double-blind trial to further validate these preliminary results.

Patients with chronic prostatitis may also benefit from treatment with quercetin. A double-blind, placebo-controlled study of thirty men with category III chronic prostatitis syndromes was conducted using 500mg of quercetin or placebo twice daily for a month. This administration was then followed by an open trial of additional bromelain and papain supplementation, used to enhance the absorption of quercetin. [9] The results showed a significant improvement in most men taking quercetin, which was increased with bromelain/papain supplementation. In addition, the therapies were well tolerated.

Quercetin has been studied successfully, in vitro, for inhibition of certain signal transduction targets related to tumor growth and activity. An in vivo study using intravenous boluses of quercetin was conducted as part of a Phase I clinical trial. [10] The results showed that in 9 of 11 patients, lymphocyte protein tyrosine phosphorylation was inhibited following administration of quercetin at one hour, which persisted to 16 hours. As well, in two of the patients, serum markers of cancer activity were decreased significantly, one of which was resistant to treatment with cisplatin, a popular chemotherapeutic agent.

Another study suggested that quercetin has significant ability to inhibit angiogenesis, a process key in tumor growth. [11] A review of vegetables in the allium family, which are typically high in quercetin, discusses epidemiological evidence that has shown higher intake of allium products being associated with reduced risks of several types of cancers. [12] The current theories of mechanistic action include; inhibition of mutagenesis, modulation of enzyme activities, inhibition of DNA adduct formation, free-radical scavenging, and effects on cell proliferation and tumor growth. One study concluded that quercetin may act as a potent chemopreventive agent of lung cancer for non-smoking Taiwanese women. [13]

A double-blind randomized, placebo-controlled trial in patients with chronic venous insufficiency (CVI) was conducted to determine the effectiveness of red vine leaf extract, which contains high levels of quercetin. [14] Patients were given either 360mg or 720mg of red vine leaf extract, or placebo over 12 weeks. The results showed that the extract significantly reduced lower leg edema and circumference, while improving key CVI-related symptoms to a clinically relevant extent. Furthermore, the edema reduction was at least equivalent to that reported for compression stockings and/or other edema-reducing agents. Both doses were tolerated equally, but the higher dose gave more sustained results.

An interesting application for quercetin is in the treatment of human African trypanosomiasis (HAT), or sleeping sickness. Quercetin directly induced the death of Trypanosoma brucei gambiense, the causative agent of HAT, without affecting normal human cell viability. [15] Quercetin caused the agent to expire via the process of apoptosis. Induced dose-dependent decreases in the levels of TNF-alpha and nitric oxide produced by activated human macrophages were key factors contributing to HAT eradication as well, as both are inflammatory mediators.

Other conditions for which quercetin may be beneficial include; hypertension, allergies, keloid and hypertrophic scars, cardiovascular disease, hepatic fibrosis, peptic ulcer, osteoporosis, musculoskeletal disorders, and neurodegenerative diseases like Alzheimer's and cataracts. [16-22]

Most studies use an oral dose of 500 milligrams of quercetin two to three times daily. Quercetin chalcone, a form of quercetin, is better absorbed in the gastrointestinal tract, lowering the dose required. However, if treating inflammatory conditions of the gastrointestinal tract, quercetin alone may be the preferred choice as it is longer lasting. Quercetin from food is often better absorbed because it is bound to chemical compounds called glycones. Taking quercetin in powder form and allowing it to directly mix with saliva in the mouth before swallowing may also enhance absorption. [23]

Quercetin Deficiency

Quercetin is a phytochemical which has many benefits throughout the body. Because it is not an essential nutrient, deficiency syndromes have not been documented.

Quercetin Toxicities

Quercetin is generally considered a safe therapeutic substance when taken in recommended doses. The majority of studies reveal the absence of adverse effects or only mild side effects.

Quercetin has been studied in combination with the chemotherapy drug cisplatin. Quercetin by itself has similar in action to cisplatin, causing gentoxicity to certain cells. However, in hepatocytes, quercetin appears to inhibit repair of cisplatin-induced DNA damage; therefore, care should be taken with this combination of therapies, as quercetin may potentiate the destruction of normal tissue. [24]

1. Annonymous. Quercetin. Alt Med Review 2001;3(2):140-143.

2. Bouriche H et al. Effect of Cleome arabica leaf extract, rutin and quercetin on soybean lipoxygenase activity and on generation of inflammatory eicosanoids by human neutrophils. Prostaglandins Leukot Essent Fatty Acids. 2005;72(3):195-201.

3. Bronner C and Landry Y. Kinetics of the inhibitory effect of flavonoids on histamine secretion from mast cells. Agents Actions 1985;16:147-151.

4. Moreira AJ et al. Quercetin prevents oxidative stress and NF-kappaB activation in gastric mucosa of portal hypertensive rats. Biochem Pharmacol. 2004;68(10):1939-46.

5. Muthian G, Bright JJ. Quercetin, a flavonoid phytoestrogen, ameliorates experimental allergic encephalomyelitis by blocking IL-12 signaling through JAK-STAT pathway in T lymphocyte. J Clin Immunol. 2004;24(5):542-52.

6. Erlund I et al. Consumption of black currants, lingonberries and bilberries increases serum quercetin concentrations. Eur J Clin Nutr. 2003;57(1):37-42.

7. Erlund I et al. Tea and coronary heart disease: the flavonoid quercetin is more bioavailable from rutin in women than in men. Arch Intern Med. 2001;161(15):1919-20.

8. Katske F et al. Treatment of interstitial cystitis with a quercetin supplement. Tech Urol. 2001;7(1):44-6.

9. Shoskes DA et al. Quercetin in men with category III chronic prostatitis: a preliminary prospective, double-blind, placebo-controlled trial. Urology. 1999;54(6):960-3.

10. Ferry DR et al. Phase I clinical trial of the flavonoid quercetin: pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. Clin Cancer Res. 1996;2(4):659-68.

11. Tan WF et al. Quercetin, a dietary-derived flavonoid, possesses antiangiogenic potential. Eur J Pharmacol. 2003;459(2-3):255-62.

12. Sengupta A, Ghosh S, Bhattacharjee S. Allium vegetables in cancer prevention: an overview. Asian Pac J Cancer Prev. 2004;5(3):237-45.

13. Lin SY et al. Protection by quercetin against cooking oil fumes-induced DNA damage in human lung adenocarcinoma CL-3 cells: role of COX-2. Nutr Cancer. 2002;44(1):95-101.

14. Kiesewetter H et al. Efficacy of orally administered extract of red vine leaf AS 195 (folia vitis viniferae) in chronic venous insufficiency (stages I-II). A randomized, double-blind, placebo-controlled trial. Arzneimittelforschung. 2000;50(2):109-17.

15. Mamani-Matsuda M et al. Quercetin induces apoptosis of Trypanosoma brucei gambiense and decreases the proinflammatory response of human macrophages. Antimicrob Agents Chemother. 2004;48(3):924-9.

16. Ibarra M et al. Effects of the flavonoid quercetin and its methylated metabolite isorhamnetin in isolated arteries from spontaneously hypertensive rats. Planta Med. 2003;69(11):995-1000.

17. Phan TT et al. Quercetin inhibits fibronectin production by keloid-derived fibroblasts. Implication for the treatment of excessive scars. J Dermatol Sci. 2003;33(3):192-4.

18. Phan TT et al. Suppression of insulin-like growth factor signalling pathway and collagen expression in keloid-derived fibroblasts by quercetin: its therapeutic potential use in the treatment and/or prevention of keloids. Br J Dermatol. 2003;148(3):544-52.

19. Lee ES et al. The flavonoid quercetin inhibits dimethylnitrosamine-induced liver damage in rats. J Pharm Pharmacol. 2003;55(8):1169-74.

20. Wattel A et al. Potent inhibitory effect of naturally occurring flavonoids quercetin and kaempferol on in vitro osteoclastic bone resorption. Biochem Pharmacol. 2003;65(1):35-42.

21. Teixeira S. Bioflavonoids: proanthocyanidins and quercetin and their potential roles in treating musculoskeletal conditions. J Orthop Sports Phys Ther. 2002;32(7):357-63.

22. Heo HJ, Lee CY. Protective effects of quercetin and vitamin C against oxidative stress-induced neurodegeneration. J Agric Food Chem. 2004;52(25):7514-7.

23. Mitchell W. Foundations of Natural Therapeutics: Biochemical Apologetics of Naturopathic Medicine. Bastyr University, Kenmore, WA.

24. Cross HJ et al. Effect of quercetin on the genotoxic potential of cisplatin. Int J Cancer. 1996;66(3):404-8.