Quercetin

Quercetin finds itself in a number of Sanctuary protocols due to the multiplicity of benefits it has to offer.   The natural substance boasts  among its most well known functions effects in ameliorating allergies, preventing oxidation of LDL cholesterol, assisting in metal detoxification, and providing anti-oxidant protection.  Lesser known benefits include in prostatitis and very mild effects on lowering blood pressure and blood sugar. 2020 has highlighted its anti-viral effects as many use it in COVID 19 protocols.

Summaries of effects:

Allergies:  The easiest and most common use of quercetin comes up when helping patients overcome a variety of allergies.  Whether suffering from sinus issues, food sensitivities, or mast cell activation, quercetin can help shift our bodies away from the histamine which underlies allergic reactions.  On one hand, it can inhibit release of histamine from mast cells (immune cells). On another hand, it can also lower IgE reactions which trigger histamine release.

Controlling mast cells and their subsequent release of histamine ranks high in the therapy for mold toxicity.  Quercetin serves this otherwise difficult hurdle to therapy.  It stabilizes mast cells so that they are less likely to release histamine or other immune stimulating chemicals.

In regular, old-fashioned allergies, many long-term allergies sufferers who have been dependent on anti-histamines and nasal steroids find that they can often wean off these pharmaceuticals partially or entirely.

Cholesterol:  Oxidation of LDL cholesterol appears to underlie advancing atherosclerosis.  Once oxidized, this LDL then triggers the immune system to cause arterial wall inflammation.  By reducing LDL oxidation, atherosclerosis can be prevented.  In a study by Graf et al, cardiovascular mortality was even reduced with quercetin intake.  This seemed to be related to its scavenging free radicals and chelating metals.

While not confirmed, given that some research links mast cells and histamine to non-cholesterol related heart attacks, I wonder if quercetin is also acting through this mechanism as well.

Metals Detoxification:  Quercetin remarkably finds a way to also protect animals from lead and cadmium toxicity through a variety of mechanisms.  These include methallothionein, nitric oxide synthases (NOS), COX-2, MAPK, and NF-kappaB (see acronym key below)>

Antioxidant:  Quercetin boasts major antioxidant capacity.  It is comparable to curcumin in its scope.

Prostatitis:  In one study, men who took quercetin 500mg twice daily for 1 month had a statistically significant improvement in prostate symptoms.  67% noted improvement versus only 20% of those on placebo therapy. Pain and quality of life improved but some urinary symptoms did not improve.

Blood Pressure and Blood Sugar:  The effects on pressure and sugar are modest at best, but should be kept in mind when prescribing.  The decrease in blood pressure was only 2-3 points in one study.  The decrease in blood sugar was barely noticeable in another study while another did not show changes at lower doses.

Viral effects:  With 2020’s excessive attention to anti-viral therapy thanks to COVID 19, several studies relating quercetin’s anti-viral effects deserve attention.  A few studies indicate that quercetin may be preventive or therapeutic with a variety of viral infections.

Other areas being researched but without adequate support for recommendations:

Sleep

Exercise

Cancer

Memory and Brain Function

Arthritis

How To take quercetin:

1. Many sources of quercetin exist in food, yet effective dosages for our symptomatic patients are rarely reached through food alone. The highest concentration can be found in capers but also moderately in the outer layers of onions. It is also found in apples, apricots, blueberries, cranberries, black plums, kale, alfalfa sprouts, green beans, broccoli, black tea, and chili powder.  Be aware however that supplementation is necessary for clinical disease treatment.   Food sources serve more for prevention.
2. For symptomatic allergies: Quercetin only works to prevent the release of histamine, meaning that once a reaction has occurred, quercetin has no immediate effect.  Most find that twice daily dosing for 3 to 4 days is necessary before noting clinical benefits.  By 7 days, the majority of benefit has occurred.  At that point, dosing could be increased if symptoms remain.  Infrequently, patients may need three times a day dosing or a higher dose.

Potential side effects:

1. Allergic reactions: As with nearly any therapy, any one can develop allergies to any chemical we give them.  Severe reactions are extremely rare with quercetin, but low grade subtle effects may occur.  Blood tests can reveal these sensitivities.
2. In mold toxic patients, nearly all bets are off in terms of reacting to chemicals or therapies. Mold patients are possibly the most sensitive patients we see. In such patients, the normally allergy-decreasing quercetin may trigger very unusual reactions.  With detox of mold, these usually resolve but at times we are not able to use quercetin in normal dosages.
3. GI symptoms: Even when taken alone, many patients have sensitive stomachs and find quercetin to cause a little nausea.  Usually this can be prevented with simultaneous food ingestion.
4. COMT interference: At one point in the recent past, many in functional medicine and nutrigenomics expressed concern that quercetin might hinder already slowed COMT function.  Catechol O methyl transferase, COMT, processes many neuro-transmitters, estrogen, and other metabolically important chemicals.  The concern centered around whether an individual with COMT 158, 62, or 199 SNPS, which already greatly reduced the enzymes function, might suffer negative consequences from a further interference.  Studies later indicate that while quercetin does slow the enzyme down considerably, the effect would only occur in a laboratory test tube where concentrations were high enough.  The amount of quercetin which a human would need to ingest in order to reach these active concentrations is unlikely without a major overdose.  Therefore, we do not restrict quercetin for patients with COMT SNPs (single nucleotide polymorphisms).

Risks:

1. Renal: A study suggested that quercetin may cause renal decline in patient already suffering from renal insufficiency.  This is not clear but caution should be taken in those individuals.  In patients with normal renal function, there does not appear to be any risk of kidney harm.

Interactions:

1. OATP1B1 transport:  Quercetin may increase uptake of the following drugs, increaeasing their concentrations:  Statin drugs for cholesterol, Estrogens, valasartan, enalapril, methotrexate, fexofenadine.
2. CYP2C9 inhibitor: Quercetin may slow the breakdown of chemicals metabolized by CYP2C9 and thus raise their levels:  diclofenac, Fluvastatin, celecoxib, glipizide, ibuprofen, losartan, phenytoin, piroxicam, warfarin, and tamoxifen.
3. CYP3A activator: Quercetin may speed up the activity of this enzyme and thus lower the levels of: midazolam.

ACRONYM KEY:

NF kappa B – Nuclear Factor kappa B.  This protein plays a central role in promoting inflammation.  A wide variety of triggers set off a cascade of downstream processes that all begin with NF kappa B.  Once NK kappa B is triggered, these downstream processes carry out the metabolic pathways which produce what we perceive as inflammation.

COX-2: Cyclo-oxygenase 2 enzyme.  This enzyme plays an important role in the inflammatory pathway.  By converting arachidonic acid, an omega 6 fatty acid associated with inflammation, into prostaglandins, COX-2 sets off a cascade of processes leading to prostaglandins which cause inflammation.  While a similar enzyme called COX-1 is always working at a relatively consistent low level, COX-2 is activated with inflammation.

NOS:  inducible Nitric Oxide Synthase.  This is one of the three enzymes responsible for producing nitric oxide in the body.  NOS2 is the gene which produces this enzyme.  This form is found in immune cells that are used to attack invaders like bacteria with oxidation.  NOS is inducible because it is turned on when a need for immune defense is identified but turned down when the perceived threat is over.

Allergies: 

Weng, Zuyi 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 vol. 7,3 (2012): e33805.

Mlcek, Jiri et al. “Quercetin and Its Anti-Allergic Immune Response.” Molecules (Basel, Switzerland) vol. 21,5 623. 12 May. 2016, doi:10.3390/molecules21050623

Jafarinia, Morteza et al. “Quercetin with the potential effect on allergic diseases.” Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology vol. 16 36. 14 May. 2020, doi:10.1186/s13223-020-00434-0

Chirumbolo, Salvatore. “The role of quercetin, flavonols and flavones in modulating inflammatory cell function.” Inflammation & allergy drug targets vol. 9,4 (2010): 263-85. doi:10.2174/187152810793358741

Kashiwabara, Misako et al. “Suppression of neuropeptide production by quercetin in allergic rhinitis model rats.” BMC complementary and alternative medicine vol. 16 132. 20 May. 2016, doi:10.1186/s12906-016-1123-z

Cholesterol:

Journal of International Society of Sports Nutrition. 2014 May 27;11:22. doi: 10.1186/1550-2783-11-22. eCollection 2014.

Quercetin intake with exercise modulates lipoprotein metabolism and reduces atherosclerosis plaque formation.

Garelnabi M1, Mahini H1, Wilson T1.

Frontiers in Pharmacology. 2017 Feb 3;8:40. doi: 10.3389/fphar.2017.00040. eCollection 2017.

Quercetin Inhibits LPS-Induced Inflammation and ox-LDL-Induced Lipid Deposition.

Xue F1, Nie X2, Shi J3, Liu Q1, Wang Z4, Li X2, Zhou J5, Su J4, Xue M1, Chen WD6, Wang YD4.

Graf B Flavonols, flavonones & human health: epidemiological evidence Journal of Medicinal Food 2005; 8: 281-90

Metal Detox:

Hu P Quercetin relieves chronic lead exposure-induced impairment of synaptic plasticity in rat gentate gyrus in vivo. Naunyn Schlmiederbergs Archives Pharmacology 2008 Jul; 378(1): 43-51

Vicente-Sánchez C., Egido J., Sánchez-González P.D., Pérez-Barriocanal F., López-Novoa J.M., Morales A.I. Effect of the flavonoid quercetin on cadmium-induced hepatotoxicity. Food Chemistry. Toxicol. 2008;46:2279–2287. doi: 10.1016/j.fct.2008.03.009.

Morales A.I., Vicente-Sánchez C., Jerkic M., Santiago J.M., Sánchez-González P.D., Pérez-Barriocanal F., López-Novoa J.M. Effect of quercetin on metallothionein, nitric oxide synthases and cyclooxygenase-2 expression on experimental chronic cadmium nephrotoxicity in rats. Toxicology and Applied Pharmacology. 2006;210:128–135. doi: 10.1016/j.taap.2005.09.006.

Liu C.M., Zheng G., Ming Q., Sun J., Cheng C. Protective effect of quercetin on lead-induced oxidative stress and endoplasmic reticulum stress in rat liver via the IRE1/JNK and PI3K/Akt pathway. Free Radical Research. 2013;47:192–201. doi: 10.3109/10715762.2012.760198.

Liu C.M., Sun Y.Z., Sun J.M., Ma J.Q., Cheng C. Protective role of quercetin against lead-induced inflammatory response in rat kidney through the ROS-mediated MAPKs and NF-κB pathway. Biochim. Biophys. Acta. 2012;1820:1693–1703. doi: 10.1016/j.bbagen.2012.06.011.

Malešev D., Kuntić V. Investigation of metal-flavonoid chelates and the determination of flavonoids via metal-flavonoid complexing reactions. J. Serbian Chem. Soc. 2007;72:921–939. doi: 10.2298/JSC0710921M.

Antioxidant:

Adv Exp Med Biol. 2011;701:283-9. doi: 10.1007/978-1-4419-7756-4_38.

Antioxidant properties of quercetin.

Zhang M1, Swarts SG, Yin L, Liu C, Tian Y, Cao Y, Swarts M, Yang S, Zhang SB, Zhang K, Ju S, Olek DJ Jr, Schwartz L, Keng PC, Howell R, Zhang L, Okunieff P.

Prostatitis:

Shoskes, D A et al. “Quercetin in men with category III chronic prostatitis: a preliminary prospective, double-blind, placebo-controlled trial.” Urology vol. 54,6 (1999): 960-3. doi:10.1016/s0090-4295(99)00358-1

Blood Pressure:

Serban, Maria-Corina et al. “Effects of Quercetin on Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.” Journal of the American Heart Association vol. 5,7 e002713. 12 Jul. 2016, doi:10.1161/JAHA.115.002713

Tamtaji, Omid R et al. “The Effects of Quercetin Supplementation on Blood Pressures and Endothelial Function Among Patients with Metabolic Syndrome and Related Disorders: A Systematic Review and Meta-analysis of Randomized Controlled Trials.” Current pharmaceutical design vol. 25,12 (2019): 1372-1384. doi:10.2174/1381612825666190513095352

Blood Sugar:

Rezvan, Neda et al. “Oral Quercetin Supplementation Enhances Adiponectin Receptor Transcript Expression in Polycystic Ovary Syndrome Patients: A Randomized Placebo-Controlled Double-Blind Clinical Trial.” Cell journal vol. 19,4 (2018): 627-633. doi:10.22074/cellj.2018.4577

Ostadmohammadi, Vahidreza et al. “Effects of quercetin supplementation on glycemic control among patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials.” Phytotherapy research : PTR vol. 33,5 (2019): 1330-1340. doi:10.1002/ptr.6334

Anti-Viral:

Somerville, Vaughan S et al. “Effect of Flavonoids on Upper Respiratory Tract Infections and Immune Function: A Systematic Review and Meta-Analysis.” Advances in nutrition (Bethesda, Md.) vol. 7,3 488-97. 16 May. 2016, doi:10.3945/an.115.010538

Prophylactic Efficacy of Quercetin 3-β-O-d-Glucoside against Ebola Virus Infection

Xiangguo Qiu, Andrea Kroeker, Shihua He, Robert Kozak, Jonathan Audet, Majambu Mbikay, Michel Chrétien

Antimicrobial Agents and Chemotherapy Aug 2016, 60 (9) 5182-5188; DOI: 10.1128/AAC.00307-16

Wong, Gary et al. “Antiviral activity of quercetin-3-β-O-D-glucoside against Zika virus infection.” Virologica Sinica vol. 32,6 (2017): 545-547. doi:10.1007/s12250-017-4057-9

Nieman, David C et al. “Quercetin reduces illness but not immune perturbations after intensive exercise.” Medicine and science in sports and exercise vol. 39,9 (2007): 1561-9. doi:10.1249/mss.0b013e318076b566

Li, Yao et al. “Quercetin, Inflammation and Immunity.” Nutrients vol. 8,3 167. 15 Mar. 2016, doi:10.3390/nu8030167

Drug Interactions:

Rastogi, H. and Jana, S. (2014), Evaluation of Inhibitory Effects of Caffeic acid and Quercetin on Human Liver Cytochrome P450 Activities, Phytother. Res., 28, pages 1873– 1878, doi: 10.1002/ptr.5220

Duan, Kai-Ming et al. “Effect of quercetin on CYP3A activity in Chinese healthy participants.” Journal of clinical pharmacology vol. 52,6 (2012): 940-6. doi:10.1177/0091270011406278

Bedada, Satish Kumar, and Prasad Neerati. “Evaluation of the effect of quercetin treatment on CYP2C9 enzyme activity of diclofenac in healthy human volunteers.” Phytotherapy research : PTR vol. 32,2 (2018): 305-311. doi:10.1002/ptr.5978

Kidney Effects:

Andres, Susanne et al. “Safety Aspects of the Use of Quercetin as a Dietary Supplement.” Molecular nutrition & food research vol. 62,1 (2018): 10.1002/mnfr.201700447. doi:10.1002/mnfr.201700447

General Effects:

Davis, J Mark et al. “Effects of the dietary flavonoid quercetin upon performance and health.” Current sports medicine reports vol. 8,4 (2009): 206-13. doi:10.1249/JSR.0b013e3181ae8959

Sanctuary Functional Medicine, under the direction of Dr Eric Potter, IFMCP MD, provides functional medicine services to Nashville, Middle Tennessee and beyond. We frequently treat patients from Kentucky, Alabama, Mississippi, Georgia, Ohio, Indiana, and more... offering the hope of healthier more abundant lives to those with chronic illness.