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.
Occurrence
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
mg.[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.[8] One study found that
organically growntomatoes had 79% more quercetin than non-organically grown fruit.[9] Quercetin is present in various kinds of
honey from different plant sources.[10]
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.[11]
The
bioavailability of quercetin in humans after oral intake is very low, with one study concluding it must be less than 1%.[15] Intravenous injection of quercetin shows a rapid decay in concentration described by a two-compartment model (initial
half-life of 8.8 minutes, terminal half-life of 2.4 hours).[15] Because it undergoes rapid and extensive metabolism, the biological effects presumed from in vitro studies are unlikely to apply in vivo.[2][16][17][18] Quercetin supplements in the
aglycone form are less
bioavailable than the quercetin
glycoside often found in foods, especially red onions.[2][19] Ingestion with high-fat foods may increase bioavailability compared to ingestion with low-fat foods,[19] and carbohydrate-rich foods may increase absorption of quercetin by stimulating
gastrointestinal motility and
colonicfermentation.[2] Whereas quercetin has been shown to be a potent anti-inflammatory compound in a variety of in vitro and in vivo bioassay models, oral quercetin in human subjects has not exhibited the desired effects.[20] Because of low solubility and poor bioavailability of quercetin, derivatives have been synthesized to overcome these challenges and enhance its biological activity, leading to compounds with improved properties for possible therapeutic applications.[21]
Metabolism
Quercetin is rapidly metabolized (via
glucuronidation) after the ingestion of quercetin foods or supplements.[22] Five metabolites (quercetin glucuronides) have been found in human plasma after quercetin ingestion.[23][22] Taken together, the quercetin glucuronides have a half-life around 11–12 hours.[22]
Compared to other
flavonoids, quercetin is one of the most effective inducers of the phase II detoxification enzymes.[25]
In vitro studies show that quercetin is a strong inhibitor of the
cytochrome P450 enzymes
CYP3A4 and
CYP2C19 and a moderate inhibitor of
CYP2D6.[26][27] Drugs that are metabolized by these pathways may have increased effect. An in vivo study found that quercetin supplementation slows the metabolism of
caffeine to a statistically significant extent in a particular genetic subpopulation, but in absolute terms the effect was almost negligible.[28]
Quercetin has been studied in
basic research and small
clinical trials.[2][30][31][32] While supplements have been promoted for the treatment of cancer and various other diseases,[2][33] there is no high-quality evidence that quercetin (via supplements or in food) is useful to treat cancer[34] or any other disease.[2][35]
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.[36][37] 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",[36][37] conditions not met by the manufacturers.
Safety
Little research has been conducted into the safety of quercetin supplementation in humans, and the results are insufficient to give confidence that the practice is safe. In particular, a lack of safety information exists 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.[38]
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.[38]
^
abcdefghij"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.
^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.
S2CID260253046.
^
abGugler, R.; Leschik, M.; Dengler, H. J. (1 March 1975). "Disposition of quercetin in man after single oral and intravenous doses". European Journal of Clinical Pharmacology. 9 (2): 229–234.
doi:
10.1007/BF00614022.
PMID1233267.
S2CID23812714.
^Wittig, Jörg; Herderich, Markus; Graefe, Eva Ulrike; Veit, Markus (April 2001). "Identification of quercetin glucuronides in human plasma by high-performance liquid chromatography–tandem mass spectrometry". Journal of Chromatography B: Biomedical Sciences and Applications. 753 (2): 237–243.
doi:
10.1016/s0378-4347(00)00549-1.
PMID11334336.
^
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.