The Antiviral and Anti-Inflammatory Potential of Quercetin
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The value of quercetin for respiratory health beyond allergies
Quercetin is another well-known member of the polyphenol family. Considered a flavonoid type of polyphenol, quercetin is found in many fruits and vegetables, including onions, apples, cherries, broccoli, tomatoes, and berries, as well as green tea.
We look to quercetin most often seasonally as a remedy for those with allergic afflictions.[1] Quercetin counteracts the allergic response by suppressing antigen-specific immunoglobulin (Ig) E antibody formation, thereby acting at a very early stage in the allergic response.[2],[3] Additionally, quercetin inhibits the release of histamine and proinflammatory substances implicated in allergic reactions.[4] By these and other mechanisms, quercetin may improve contact dermatitis and photosensitivity,[5] allergic rhinitis,[6] and asthma.[7],[8]
In addition to these anti-allergic effects, quercetin helps to balance the Th1:Th2 immune response, downregulating production of Th2 allergic response-related cytokines, such as interleukin (IL)-4, and increasing interferon (IFN)-γ,[9] a key Th1 cytokine involved in the response against viral invaders and the development of immunity to pathogens.[10],[11],[12],[13]
Quercetin further shows respiratory tract affinity in the protection it offers against oxidative damage and inflammation associated with particulate matter exposure.
Studies have shown numerous mechanisms by which quercetin and other flavonoids can reduce infectivity of a wide variety of respiratory and other viruses,[14] including influenza, adenovirus, rhinovirus, and coronaviruses.[15],[16],[17],[18] Quercetin further shows respiratory tract affinity in the protection it offers against oxidative damage and inflammation associated with particulate matter exposure.[19] Quercetin happens to be found at fairly high levels in St. John’s wort (Hypericum perforatum),[20] and may be one of the constituents that contributes to its mood-stabilizing and antiviral effects.[21],[22],[23],[24],[25]
Quercetin helps protect the body against reactive oxygen species, although studies show it also can have pro-oxidant effects.[26],[27],[28] Although we think of pro-oxidants negatively, they are activators of our body’s endogenous antioxidant and protective detoxification enzyme transcription by turning on the Nrf2/ARE pathway. In animals, quercetin supplementation has been observed to increase levels of alpha-tocopherol (a form of vitamin E) while decreasing markers of lipid peroxidation, however variable effects on glutathione levels have been shown.[29],[30] Providing additional antioxidants along with quercetin such as vitamin C and glutathione may help to negate the pro-oxidant effects and enhance quercetin recycling.[14],[31] Indeed, vitamin C appears to enhance the activity of quercetin, in part by stabilizing the quercetin molecule itself.[32]
Human studies with quercetin
In healthy individuals, quercetin supplementation has been shown to significantly reduce the incidence of upper respiratory tract infections.
Clinical studies have also shown quercetin has anti-inflammatory and antioxidant effects.[33] These effects were seen more clearly in diseases such as sarcoidosis (a condition that primarily affects the lungs) where there is a high level of oxidative stress and inflammation associated with the pathology.[34] Quercetin has also been shown to reduce pro-inflammatory cytokine production triggered by lipopolysaccharide (LPS) stimulation of ex vivo blood samples from patients with idiopathic pulmonary fibrosis, suggesting it may be of benefit in this population as well.[35]
In healthy individuals, quercetin supplementation has been shown to significantly reduce the incidence of upper respiratory tract infection (URTI) in trained male cyclists[36] and the number of URTI sick days and symptom severity in physically fit subjects over the age of 40.[37] An extensive recent review looks at numerous mechanisms by which the combination of quercetin with vitamin C may be effective as a prophylactic for prevention of highly prevalent respiratory infections.[14] Supplementation of quercetin also has been shown in humans to have antiviral potential in individuals with chronic hepatitis C,[38] and to have a positive impact on blood pressure,[39] cholesterol profiles,[40] and other markers of cardiovascular disease risk.[41],[42]
Quercetin is typically well-tolerated and has been demonstrated to be safe in humans when taken acutely up to 5 g/day.,[38] And clearly, it is worthy of consideration for more than just allergies.
Click here to see References
[1] Mlcek J, et al. Quercetin and its anti-allergic immune response. Molecules. 2016 May 12;21(5):623.
[2] Singh A, et al. Dietary polyphenols in the prevention and treatment of allergic diseases. Clin Exp Allergy. 2011 Oct;41(10):1346-59.
[3] Marzocchella L, et al. Dietary flavonoids: molecular mechanisms of action as anti-inflammatory agents. Recent Pat Inflamm Allergy Drug Discov. 2011 Sep;5(3):200-20.
[4] Chirumbolo S. The role of quercetin, flavonols and flavones in modulating inflammatory cell function. Inflamm Allergy Drug Targets. 2010 Sep;9(4):263-85.
[5] Weng Z, et al. Quercetin is more effective than cromolyn in blocking human mast cell cytokine release and inhibits contact dermatitis and photosensitivity in humans. PLoS One. 2012;7(3):e33805.
[6] Sagit M, et al. Effectiveness of quercetin in an experimental rat model of allergic rhinitis. Eur Arch Otorhinolaryngol. 2017 Aug;274(8):3087-95.
[7] Joskova M, et al. Acute bronchodilator effect of quercetin in experimental allergic asthma. Bratisl Lek Listy. 2011;112(1):9-12.
[8] Fortunato LR, et al. Quercetin: a flavonoid with the potential to treat asthma. Braz J Pharm Sci. 2012 Dec;48(4):589-99.
[9] Nair MP, et al. The flavonoid, quercetin, differentially regulates Th-1 (IFNgamma) and Th-2 (IL4) cytokine gene expression by normal peripheral blood mononuclear cells. Biochim Biophys Acta. 2002 Dec 16;1593(1):29-36.
[10] Chesler DA, Reiss CS. The role of IFN-gamma in immune responses to viral infections of the central nervous system. Cytokine Growth Factor Rev. 2002 Dec;13(6):441-54.
[11] Huang S, et al. Immune response in mice that lack the interferon-gamma receptor. Science. 1993 Mar 19;259(5102):1742-5.
[12] Zhou J, et al. Immunogenicity, safety, and protective efficacy of an inactivated SARS-associated coronavirus vaccine in rhesus monkeys. Vaccine. 2005 May 2;23(24):3202-9.
[13] Spruth M, et al. A double-inactivated whole virus candidate SARS coronavirus vaccine stimulates neutralising and protective antibody responses. Vaccine. 2006 Jan 30;24(5):652-61.
[14] Colunga Biancatelli RML, et al. Quercetin and vitamin C: an experimental, synergistic therapy for the prevention and treatment of SARS-CoV-2 related disease (COVID-19). Front Immunol. 2020 Jun 19;11:1451.
[15] Jo S, et al. Characteristics of flavonoids as potent MERS-CoV 3C-like protease inhibitors. Chem Biol Drug Des. 2019 Dec;94(6):2023-30.
[16] Chiang LC, et al. In vitro antiviral activities of Caesalpinia pulcherrima and its related flavonoids. J Antimicrob Chemother. 2003 Aug;52(2):194-8.
[17] Yi L, et al. Small molecules blocking the entry of severe acute respiratory syndrome coronavirus into host cells. J Virol. 2004 Oct;78(20):11334-9.
[18] Gansukh E, et al. Nature nominee quercetin’s anti-influenza combat strategy-demonstrations and remonstrations. Rev Med Virol. 2017 May;27(3):e1930.
[19] Jin X, et al. Amelioration of particulate matter-induced oxidative damage by vitamin C and quercetin in human bronchial epithelial cells. Chemosphere. 2016 Feb;144:459-66.
[20] Schulz HU, et al. Investigation of the bioavailability of hypericin, pseudohypericin, hyperforin and the flavonoids quercetin and isorhamnetin following single and multiple oral dosing of a hypericum extract containing tablet. Arzneimittelforschung. 2005;55(1):15-22.
[21] Chimenti F, et al. Quercetin as the active principle of Hypericum hircinum exerts a selective inhibitory activity against MAO-A: extraction, biological analysis, and computational study. J Nat Prod. 2006 Jun;69(6):945-9.
[22] Silva B, et al. Quercetin, kaempferol and biapigenin from Hypericum perforatum are neuroprotective against excitotoxic insults. Neurotox Res. 2008 May-Jun;13(3-4):265-79.
[23] Butterweck V, et al. Flavonoids from Hypericum perforatum show antidepressant activity in the forced swimming test. Planta Med. 2000 Feb;66(1):3-6.
[24] Chen H, et al. Antiviral activity against infectious bronchitis virus and bioactive components of Hypericum perforatum L. Front Pharmacol. 2019 Oct 29;10:1272.
[25] Axarlis S, et al. Antiviral in vitro activity of Hypericum perforatum L. extract on the human cytomegalovirus (HCMV). Phytotherapy Research. 1998 Nov;12(7):507-11.
[26] Boots AW, et al. The quercetin paradox. Toxicol Appl Pharmacol. 2007 Jul 1;222(1):89-96.
[27] Xu D, et al. Antioxidant activities of quercetin and its complexes for medicinal application. Molecules. 2019 Mar 21;24(6):1123.
[28] Choi EJ, et al. Anti- and prooxidant effects of chronic quercetin administration in rats. Eur J Pharmacol. 2003 Dec 15;482(1-3):281-5.
[29] Xu D, et al. Antioxidant activities of quercetin and its complexes for medicinal application. Molecules. 2019 Mar 21;24(6):1123.
[30] Choi EJ, et al. Anti- and prooxidant effects of chronic quercetin administration in rats. Eur J Pharmacol. 2003 Dec 15;482(1-3):281-5.
[31] Boots AW, et al. Oxidized quercetin reacts with thiols rather than with ascorbate: implication for quercetin supplementation. Biochem Biophys Res Commun. 2003 Aug 29;308(3):560-5.
[32] Kallio J, et al. Vitamin C inhibits Staphylococcus aureus growth and enhances the inhibitory effect of quercetin on growth of Escherichia coli in vitro. Planta Med. 2012 Nov;78(17):1824-30.
[33] Javadi F, et al. The effect of quercetin on inflammatory factors and clinical symptoms in women with rheumatoid arthritis: a double-blind, randomized controlled trial. J Am Coll Nutr. 2017 Jan;36(1):9-15.
[34] Boots AW, et al. Quercetin reduces markers of oxidative stress and inflammation in sarcoidosis. Clin Nutr. 2011 Aug;30(4):506-12.
[35] Veith C, et al. The disturbed redox-balance in pulmonary fibrosis is modulated by the plant flavonoid quercetin. Toxicol Appl Pharmacol. 2017 Dec 1;336:40-48.
[36] Nieman DC, et al. Quercetin reduces illness but not immune perturbations after intensive exercise. Med Sci Sports Exerc. 2007 Sep;39(9):1561-9.
[37] Heinz SA, et al. Quercetin supplementation and upper respiratory tract infection: a randomized community clinical trial. Pharmacol Res. 2010 Sep;62(3):237-42.
[38] Lu NT, et al. A phase I dose escalation study demonstrates quercetin safety and explores potential for bioflavonoid antivirals in patients with chronic hepatitis C. Phytother Res. 2016 Jan;30(1):160-8.
[39] Brüll V, et al. Effects of a quercetin-rich onion skin extract on 24 h ambulatory blood pressure and endothelial function in overweight-to-obese patients with (pre-)hypertension: a randomised double-blinded placebo-controlled cross-over trial. Br J Nutr. 2015 Oct 28;114(8):1263-77.
[40] Talirevic E, Jelena S. Quercetin in the treatment of dyslipidemia. Med Arh. 2012;66(2):87-8.
[41] Nishimura M, et al. Effect of daily ingestion of quercetin-rich onionpowder for 12 weeks on visceral fat: a randomised, double-blind, placebo-controlled, parallel-group study. Nutrients. 2019 Dec 28;12(1):91.
[42] Egert S, et al. Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype: a double-blinded, placebo-controlled cross-over study. Br J Nutr. 2009 Oct;102(7):1065-74.
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Dr. Carrie Decker
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