Quercetin

Reading time: 7 – 11 minutes

Quercetin is a polyphenol, one of a number of water-soluble plant pigments called flavonoids (meaning class of plant secondary metabolites known for their antioxidant activity) that are largely responsible for the color of many flowers, fruits and vegetables. High concentrations of quercetin are found in apples, onions, tea and red wine [1]. Other sources of quercetin include olive oil, grapes, broccoli, cauliflower, cabbage, dark cherries and dark berries such as blueberries, blackberries and bilberries. The average U.S. citizen eating a normal, healthy diet including fruits and vegetables consumes approximately 25-50 mg of quercetin/day. Quercetin and other flavonoids (also referred to as bioflavonoids) cannot be produced in the human body.

Quercetin is a powerful antioxidant; from a range of dietary flavonoids, quercetin was found to be the most effective inhibitor of oxidative damage to LDL (bad) cholesterol in vitro [2], thereby reducing the risk of developing atherosclerosis [3]. In contrast, another study found that quercetin had mostly prooxidant effects [4]. However, when mixed with other phenolic compounds, significant antioxidant capacity was identified, indicating a synergistic effect. Quercetin may lower blood pressure by exhibiting coronary vasorelaxation (meaning reduction in tension of the blood vessel walls) properties [5-7].

A number of research studies have demonstrated that quercetin is a natural antihistamine and anti-inflammatory [8-10]. Indeed, quercetin is unique in its ability to inhibit TNF-alpha (a cytokine involved in systemic inflammation) gene expression [11]. Quercetin may also function as an antiviral agent [12-13]. A recent study reports that it may boost the immune system and help maintain mental performance.

Studies have shown that quercetin exhibits anticancer effects [14]. A number of phase I clinical trials have been performed with quercetin evaluating pharmacokinetics [15] and adenoma regression [16]. A combination of curcumin and quercetin was evaluated to regress adenomas in patients with familialadenomatous polyposis (FAP), an autosomal-dominant disorder characterized by the development of colorectal adenomas and eventual colorectal cancer. The study found that the combination appeared to decreased polyp number and size from baseline after 6 months of treatment [16].

Epidemiologic data indicates that reduction in colorectal cancer risk associated with the highest 25% of data vs. the lowest 25% was largest for quercetin and catechin [17]. Overall, flavonoids showed strong and linear inverse associations with colorectal cancer risk. Large-scale genomic studies in colon cancer cells suggest that quercetin affects the expression of genes involved in cell cycle control [18-19]. Flavonoids also modulate cell cycle progression in prostate cancer cells [20-21].

A recent review assessing the contribution of dietary flavonoids to the total antioxidant capacity of plasma in humans concluded that the large increase in plasma total antioxidant capacity observed after the consumption of flavonoid-rich foods is not caused by the flavonoids themselves, but is likely the consequence of increased uric acid levels [22]. A potent antioxidant, uric acid is a normal constituent of the body and is the end product of purine (meaning the nucleotides adenine and guanine, two of the four building blocks of RNA and DNA) metabolism. Because the increased plasma concentration of uric acid is much greater than the concentration of flavonoids, the change in uric acid levels is thought to be responsible for the relatively large increase in plasma total antioxidant capacity after consumption of flavonoid-rich foods. Most uric acid produced in the body is excreted by the kidneys. However, it has been proposed that renal uric acid clearance is regulated by an unknown signal that is issued in response to the level of oxidative stress [23], allowing the kidneys to reabsorb the potent antioxidant when needed.

Flavonoids have been shown to induce detoxifying Phase II enzymes [24-25], indicating that they are recognized by the body as foreign compounds. Thus, it has been proposed that the ability of flavonoids to induce detoxifying enzymes may be a major mechanism by which flavonoids protect against mutagens and carcinogens, and act as cancer chemopreventive agents [22].

References

1. Sampson et al. Flavonol and flavone intakes in US health professionals. J Am Diet Assoc. 2002 Oct;102(10):1414-20.
   View abstract
2. O’Reilly et al. Flavonoids protect against oxidative damage to LDL in vitro: use in selection of a flavonoid rich diet and relevance to LDL oxidation resistance ex vivo? Free Radic Res. 2000 Oct;33(4):419-26.
   View abstract
3. Negre-Salvayre et al. Quercetin Prevents the Cytotoxicity of Oxidized LDL on Lymphoid Cell Lines. Free Radic Biol Med. 1992;12(2):101-06.
   View abstract
4. Cirico and Omaye. Additive or synergetic effects of phenolic compounds on human low density lipoprotein oxidation. Food Chem Toxicol. 2006 Apr;44(4):510-6. Epub 2005 Oct 10.
   View abstract
5. Rendig et al. Effects of red wine, alcohol, and quercetin on coronary resistance and conductance arteries. J Cardiovasc Pharmacol. 2001 Aug;38(2):219-27.
   View abstract
6. Duarte et al. Effects of chronic quercetin treatment on hepatic oxidative status of spontaneously hypertensive rats. Mol Cell Biochem. 2001 May;221(1-2):155-60.
   View abstract
7. Flesch et al. Effects of red and white wine on endothelium-dependent vasorelaxation of rat aorta and human coronary arteries. Am J Physiol. 1998 Oct;275(4 Pt 2):H1183-90.
   View abstract
8. Middleton and Drzewiecki. Flavonoid inhibition of human basophil histamine release stimulated by various agents. Biochem Pharmacol. 1984 Nov 1;33(21):3333-8.
   View abstract
9. Taguchi et al. Pharmacological studies of Houttuyniae herba: the anti-inflammatory effect of quercitrin. Yakugaku Zasshi. 1993 Apr;113(4):327-33.
   View abstract
10. Loggia Della et al. Anti-inflammatory Activity of Benzopyrones that are Inhibitors of Cyclo- and Lipo-oxygenase. Pharmacol Res Commun. 1988 Dec;20 Suppl 5:91-4.
    View abstract
11. Wadsworth et al. Effects of Ginkgo biloba extract (EGb 761) and quercetin on lipopolysaccharide-induced signaling pathways involved in the release of tumor necrosis factor-alpha. Biochem Pharmacol. 2001 Oct 1;62(7):963-74.
    View abstract
12. Kaul et al. Antiviral effect of flavonoids on human viruses. J Med Virol. 1985 Jan;15(1):71-9.
    View abstract
13. Lyu et al. 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.
    View abstract
14. Morrow et al. Dietary supplementation with the anti-tumour promoter quercetin: its effects on matrix metalloproteinase gene regulation. Mutat Res. 2001 Sep 1;480-481:269-76.
    View abstract
15. Ferry et al. Phase I clinical trial of the flavonoid quercetin: pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. Clin Cancer Res. 1996 Apr;2(4):659-68.
    View abstract
16. Cruz-Correa et al. Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis. Clin Gastroenterol Hepatol. 2006 Aug;4(8):1035-8. Epub 2006 Jun 6.
    View abstract
17. Theodoratou et al. Dietary flavonoids and the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2007 Apr;16(4):684-93.
    View abstract
18. van Erk et al. Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. Epub 2004 Apr 30.
    View abstract
19. Murtaza et al. A preliminary investigation demonstrating the effect of quercetin on the expression of genes related to cell-cycle arrest, apoptosis and xenobiotic metabolism in human CO115 colon-adenocarcinoma cells using DNA microarray. Biotechnol Appl Biochem. 2006 Jul;45(Pt 1):29-36.
    View abstract
20. Kobayashi et al. Effect of flavonoids on cell cycle progression in prostate cancer cells. Cancer Lett. 2002 Feb 8;176(1):17-23.
    View abstract
21. Knowles et al. Flavonoids suppress androgen-independent human prostate tumor proliferation. Nutr Cancer. 2000;38(1):116-22.
    View abstract
22. Lotito and Frei. Consumption of flavonoid-rich foods and increased plasma antioxidant capacity in humans: cause, consequence, or epiphenomenon? Free Radic Biol Med. 2006 Dec 15;41(12):1727-46. Epub 2006 Jun 3.
    View abstract
23. Kirschbaum B. Renal regulation of plasma total antioxidant capacity. Med Hypotheses. 2001 Jun;56(6):625-9.
    View abstract
24. Kong et al. Induction of xenobiotic enzymes by the MAP kinase pathway and the antioxidant or electrophile response element (ARE/EpRE). Drug Metab Rev. 2001 Aug-Nov;33(3-4):255-71.
    View abstract
25. Walle and Walle. Induction of human UDP-glucuronosyltransferase UGT1A1 by flavonoids-structural requirements. Drug Metab Dispos. 2002 May;30(5):564-9.
    View abstract