UV visible spectrum of quercetin, with lambda max at 369 nm
Quercetin is a plant flavonol from the flavonoid group of polyphenols. It is found in many fruits, vegetables, leaves, seeds, and grains; capers, red onions, and kale are common foods containing appreciable amounts of it.[2][3] It has a bitter flavor and is used as an ingredient in dietary supplements, beverages, and foods.
Quercetin is a flavonoid widely distributed in nature.[2] The name has been used since 1857, and is derived from quercetum (oak forest), after the oak genus Quercus.[4][5] It is a naturally occurring polar auxin transport inhibitor.[6]
Quercetin is one of the most abundant dietary flavonoids,[2][3] with an average daily consumption of 25–50 milligrams.[7]
In red onions, higher concentrations of quercetin occur in the outermost rings and in the part closest to the root, the latter being the part of the plant with the highest concentration.[9] One study found that organically growntomatoes had 79% more quercetin than non-organically grown fruit.[10] Quercetin is present in various kinds of honey from different plant sources.[11]
Naringenin is converted into eriodictyol using flavanoid 3′-hydroxylase. Eriodictyol is then converted into dihydroquercetin with flavanone 3-hydroxylase, which is then converted into quercetin using flavonol synthase.[12]
The bioavailability of quercetin in humans is low and highly variable (0–50%), and it is rapidly cleared with an elimination half-life of 1–2 hours after ingesting quercetin foods or supplements.[16] Following dietary ingestion, quercetin undergoes rapid and extensive metabolism that makes the biological effects presumed from in vitro studies unlikely to apply in vivo.[17][18][19]
Quercetin supplements in the aglycone form are far less bioavailable than the quercetin glycoside often found in foods, especially red onions.[2][20] Ingestion with high-fat foods may increase bioavailability compared to ingestion with low-fat foods,[20] and carbohydrate-rich foods may increase absorption of quercetin by stimulating gastrointestinal motility and colonicfermentation.[2]
Compared to other flavonoids quercetin is one of the most effective inducers of the phase II detoxification enzymes.[22]
Quercetin is a strong inhibitor of the cytochrome P450 enzymes CYP3A4 and CYP2D6.[23] Drugs that are metabolized by these pathways may have increased effect.
Quercetin has been reported to inhibit the oxidation of other molecules and hence is classified as an antioxidant in vitro.[17] It contains a polyphenolic chemical substructure that stops oxidation in vitro by acting as a scavenger of free radicals. Quercetin has been shown to inhibit the PI3K/AKT pathway leading to downregulation of the anti-apoptotic protein Bcl-w.[24][25] Quercetin activates or inhibits the activities of a number of proteins in vitro. For example, it is a nonspecific protein kinase enzyme inhibitor.[17]
In 2010, the FDA acknowledged high-purity quercetin as GRAS for use as an ingredient in various specified food categories at levels up to 500 milligrams per serving.[26]
Quercetin has been studied in basic research and small clinical trials.[2][27][28][29] While supplements have been promoted for the treatment of cancer and various other diseases,[2][30] there is no high-quality evidence that quercetin (via supplements or in food) is useful to treat cancer[31] or any other disease.[2][32]
The US Food and Drug Administration has issued warning letters to several manufacturers advertising on their product labels and websites that quercetin product(s) can be used to treat diseases.[33][34] The FDA regards such quercetin advertising and products as unapproved – with unauthorized health claims concerning the anti-disease products – as defined by "sections 201(g)(1)(B) and/or 201 (g)(1)(C) of the Act [21 U.S.C. § 321(g)(1)(B) and/or 21 U.S.C. § 321(g)(1)(C)] because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease",[33][34] conditions not met by the manufacturers.
There has been little research into the safety of quercetin supplementation in humans, and the results are insufficient to give confidence that the practice is safe. In particular, there is a lack of safety information on the effect of quercetin supplementation for pregnant women, breastfeeding women, children, and adolescents. The hormonal effects of quercetin found in animal studies raise the suspicion of a parallel effect in humans, particularly in respect of estrogen-dependent tumors.[35]
Quercetin supplementation can interfere with the effects of medications. The precise nature of this interaction is known for some common medicines, but for many, it is not.[35]
^ abcdefghi"Flavonoids". Micronutrient Information Center, Linus Pauling Institute, Oregon State University, Corvallis, OR. November 2015. Retrieved 1 April 2018.
^Formica JV, Regelson W (1995). "Review of the biology of quercetin and related bioflavonoids". Food and Chemical Toxicology. 33 (12): 1061–80. doi:10.1016/0278-6915(95)00077-1. PMID8847003.
^Justesen U, Knuthsen P (May 2001). "Composition of flavonoids in fresh herbs and calculation of flavonoid intake by use of herbs in traditional Danish dishes". Food Chemistry. 73 (2): 245–50. doi:10.1016/S0308-8146(01)00114-5.
^Slimestad R, Fossen T, Vågen IM (December 2007). "Onions: a source of unique dietary flavonoids". Journal of Agricultural and Food Chemistry. 55 (25): 10067–80. doi:10.1021/jf0712503. PMID17997520.
^Mitchell AE, Hong YJ, Koh E, Barrett DM, Bryant DE, Denison RF, Kaffka S (Jul 2007). "Ten-year comparison of the influence of organic and conventional crop management practices on the content of flavonoids in tomatoes". Journal of Agricultural and Food Chemistry. 55 (15): 6154–9. doi:10.1021/jf070344+. PMID17590007.
^Petrus K, Schwartz H, Sontag G (Jun 2011). "Analysis of flavonoids in honey by HPLC coupled with coulometric electrode array detection and electrospray ionization mass spectrometry". Analytical and Bioanalytical Chemistry. 400 (8): 2555–63. doi:10.1007/s00216-010-4614-7. PMID21229237. S2CID24796542.
^Juergenliemk G, Boje K, Huewel S, Lohmann C, Galla HJ, Nahrstedt A (Nov 2003). "In vitro studies indicate that miquelianin (quercetin 3-O-beta-D-glucuronopyranoside) is able to reach the CNS from the small intestine". Planta Medica. 69 (11): 1013–7. doi:10.1055/s-2003-45148. PMID14735439.
^Miles SL, McFarland M, Niles RM (2014). "Molecular and physiological actions of quercetin: need for clinical trials to assess its benefits in human disease". Nutrition Reviews. 72 (11): 720–34. doi:10.1111/nure.12152. PMID25323953.
^ abKing JL (2 March 2017). "Warning Letter to Cape Fear Naturals". Inspections, Compliance, Enforcement, and Criminal Investigations, US Food and Drug Administration. Retrieved 29 November 2018.
^ abPace R (17 April 2017). "Warning Letter to DoctorVicks.com". Inspections, Compliance, Enforcement, and Criminal Investigations, US Food and Drug Administration. Retrieved 29 November 2018.
^ abAndres S, Pevny S, Ziegenhagen R, Bakhiya N, Schäfer B, Hirsch-Ernst KI, Lampen A (January 2018). "Safety Aspects of the Use of Quercetin as a Dietary Supplement". Mol Nutr Food Res (Review). 62 (1). doi:10.1002/mnfr.201700447. PMID29127724. S2CID24772872.