Quercetin

Scientific Name(s): 2-(3,4-Dihydroxyphenyl)-3,5,7-trihydroxy-4H-1-benzopyran-4-one, 3, 3′, 4′, 5, 7-pentahydroxy-2-phenylchromen-4-one, 3,3′,4′,5,7-pentahydroxyflavone
Common Name(s): Pentahydroxyflavone, Quercetin, Quercetine, Vitamin P

Medically reviewed by Drugs.com. Last updated on Dec 9, 2024.

Clinical Overview

Use

Interest in quercetin as an antioxidant is ongoing. Chemoprotective and antihypertensive effects show promise, but clinical studies are limited. Preliminary data indicate potential benefit for improving adaptive and social functioning in children with autism.

Dosing

Although specific evidence to support dosing recommendations is limited, most clinical studies use quercetin 500 to 1,000 mg per day in divided doses.

Contraindications

Contraindications have not been identified. Avoid coadministration with the cardiac glycoside digoxin.

Pregnancy/Lactation

Generally recognized as safe (GRAS) when consumed as food. Avoid dosages above those found in foods because information regarding safety and efficacy in pregnancy and lactation is lacking for such doses. Fetal growth retardation was observed in a study in rats exposed to quercetin by oral gavage.

Interactions

See Drug Interactions section.

Adverse Reactions

No clinically important adverse effects were reported in clinical studies.

Toxicology

Oral supplemental doses of up to 1,000 mg per day for as long as 12 weeks showed no evidence of toxicity. However, data on long-term safety at high doses are lacking, and concerns regarding carcinogenicity remain unresolved. Nephrotoxicity has been reported with high doses of intravenous (IV) quercetin.

Source

The flavonol quercetin is found as glycosides in many vegetables and fruits, as well as in seeds, nuts, flowers, bark, and leaves. Rich sources of quercetin include apples, asparagus, berries, Brassica vegetables (eg, broccoli), capers, grapes, onions, shallots, tea, and tomatoes. Quercetin is also found in large amounts in ginkgo, St. John’s wort, and elder. The outermost layers of onions and dried, not fresh, shallots are rich in quercetin.1, 2, 3, 4, 5 See also Onion monograph.

History

Initially, quercetin was considered to be a vitamin and given the name "vitamin P." It was identified in the 1930s, but was slow to gain recognition because it did not seem to be an essential micronutrient. As epidemiological studies in the 1990s pointed to the benefits of flavonoids in cardiovascular health, more researchers started investigating quercetin in depth.6

Chemistry

Quercetin (3, 3′, 4′, 5, 7-pentahydroxy-2-phenylchromen-4-one) is a flavonol, sharing the common hydroxylated 3-ringed structure with attached hydroxyl groups of other flavonoids.2 Quercetin is bright yellow and soluble in alcohol and lipids, but poorly soluble in hot water and insoluble in water. The aglycone form is more lipophilic than quercetin glycosides such as rutinoside from tea, and is absorbed more readily than glycoside forms, which must be hydrolyzed to release quercetin. Analytical techniques for the identification of quercetin have been described.1, 5, 7, 8, 9

Uses and Pharmacology

Anti-inflammatory activity

Clinical data

Equivocal data have been published on the anti-inflammatory effects of quercetin(13, 34, 35, 53) Reduced markers of inflammation with quercetin supplementation have been demonstrated in sarcoidosis patients and those with prehypertension.(13, 53) However, no effect on immune measures or inflammation was found in healthy community-dwelling, adult women taking supplemental quercetin 1,000 mg per day over 12 weeks.(34) The effect of quercetin on inflammatory markers was assessed in a double-blind, randomized, placebo-controlled study conducted in 88 adults (98% males) 35 to 65 years of age who had experienced their first myocardial infarction within the past 6 to 8 weeks. Quercetin 500 mg/day or placebo was administered for 8 weeks. Data demonstrated no significant difference between groups in tumor necrosis factor-alpha, hs-C-reactive protein (CRP), or interleukin (IL)-6. Likewise, no differences were noted between groups in overall quality of life, anthropometric measures, physical activity, or blood pressure. No adverse events were reported in the quercetin group.(56)

Antimicrobial effects

Clinical data

A reduction in sick days for respiratory illness was found in middle-aged and elderly subgroups.(35) Antimicrobial effects against HIV and Helicobacter pylori have also been described.(1)

Based on data from 4,521 healthy participants enrolled in 20 randomized controlled trials (including 3 studies with quercetin), meta-analyses demonstrated that flavonoid-containing supplements were safe and effective in preventing acute respiratory tract infections (ARTIs) compared to controls with a relative risk (RR) of 0.81 (95% confidence interval [CI], 0.74 to 0.89; P<0.001) and low heterogeneity. A reduction in mean ARTI sick days was also observed with the supplements; however, heterogeneity was significant (weighted mean difference [WMD], −0.56; 95% CI, −1.04 to −0.08; P=0.021). In subgroup analysis, significance in mean ARTI sick days was retained with flavonoid mixtures (ie, aged garlic extract, cranberry, elderberry, green tea) but not with use of single flavonoids (ie, quercetin, catechin). Pooled results from 16 of the trials indicated that adverse reactions were not increased in the flavonoid supplement groups compared to controls.(95)

Antioxidant activity

Animal data

Quercetin exhibits potent antioxidant activity in experimental models and in animal studies.(1, 7, 10, 11, 12)

Clinical data

Patients with sarcoidosis showed increased plasma antioxidant capacity and reduced markers of oxidative stress and inflammation with quercetin supplementation.(7, 13) However, in a clinical study of quercetin's effect on hypertension, none was found on markers of oxidative stress,(14) and no antioxidant effects were observed in healthy volunteers despite increased plasma quercetin levels.(7) In a double-blind, randomized, placebo-controlled study (N=88; 98% males) in adults who had experienced their first myocardial infarction within the past 6 to 8 weeks, quercetin 500 mg/day for 8 weeks demonstrated an increase in total antioxidant capacity compared to placebo.(56)

Autism

Data from a small, prospective, open-label trial (n = 40; 87.5% boys) in children with autism spectrum disorder showed significant improvement in adaptive functioning and overall behavior after 26-week administration of a supplement containing luteolin from chamomile (100 mg), quercetin (70 mg), and the quercetin glycoside rutin (30 mg); 1 capsule per 10 kg of weight was given daily with food. Changes in raw and age-equivalent scores were significant for all domains except communication raw scores and were greater than those expected by maturation per se. No major adverse effects were documented; however, 6 children from the original 50 enrolled withdrew due to increased irritability caused by the formulation.(50)

Cancer

Animal data

In vitro and animal studies have attempted to elucidate possible mechanisms of action for quercetin in cancer. Aside from its potent scavenging of reactive oxygen and nitrogen species and metal chelation, such mechanisms include antiproliferative, growth-suppressing, and antiangiogenesis activity; inhibition of telomerase and induction of senescence and cell death; and activation of immune and autophagic activity. Studies in rodents have included cancers of the colon, small intestine, tongue, skin, lung, and mammary gland. Other in vivo studies have used melanoma and prostate cancer cells. Quercetin also demonstrates estrogenic activity and may exert a direct effect on androgen receptors in prostate cancer cells.(1, 8, 15, 16, 17, 18, 19, 20, 21)

Clinical data

Clinical trials are lacking to support findings from epidemiological and animal studies. Phase 1 (safety) clinical studies have shown positive results; however, the number of participants was too small to draw conclusions. Other studies have used mixed preparations of quercetin with curcumin or are of limited robustness.(1, 22)

Cardiovascular disease

Animal data

Animal models and studies using isolated cardiovascular tissues suggest a role for quercetin in cardiovascular disease.(1, 15) However, not all effects observed in animal studies have translated to similar effects in humans.(23, 24) Antioxidant effects, including reduced low-density lipoprotein oxidation, decreased experimental reperfusion injury, improved endothelial function, decreased inflammation, and anti-aggregating and antihypertensive effects of quercetin have been demonstrated mostly in rodents.(1, 15, 24) Improved cholesterol profiles and decreased insulin resistance have also been demonstrated,(6, 15) while a role for quercetin metabolites has also been suggested.(25)

Clinical data

Epidemiological studies on the role of flavonoids in decreasing risk factors of cardiovascular morbidity support a place for quercetin.(1, 15) Studies in healthy volunteers and among patients with prehypertension (systolic blood pressure [BP] 120 to 139 mm Hg and diastolic BP 80 to 89 mm Hg) have found no effect of quercetin supplementation on blood pressure.(14, 26) In 23 patients with stage 1 hypertension (systolic BP 140 to 159 mm Hg, diastolic BP 90 to 99 mm Hg), quercetin 730 mg per day over 28 days reduced systolic pressure by 7 mm Hg (±2) and diastolic pressure by 5 mm Hg (±2). Mean arterial pressure was also reduced. Measures of oxidative stress, however, were not affected.(14) In a trial of overweight patients, systolic BP was reduced by 2.6 mm Hg (P < 0.01) in all participants and by 3.7 mm Hg (P < 0.01) in participants with hypertension who consumed quercetin 150 mg per day over 6 weeks.(27) Another clinical trial suggested that the efficacy of quercetin is dependent on the apolipoprotein (Apo) genotype, with subjects presenting with subtype ApoE 3 demonstrating decreased systolic pressure, while those with subtype ApoE 4 did not.(28) Inhibition of platelet aggregation and postulated reductions in the risk of thrombosis have been shown in healthy volunteers given quercetin alone and as onion soup.(29, 30) Limited studies evaluating quercetin’s effect on lipids have produced equivocal results.(28, 31)

Endothelial dysfunction and inflammation biomarkers were evaluated after 35 prehypertensive adults ingested pure epicatechin 100 mg/day and quercetin-3-glucoside 160 mg/day for 4 weeks in a placebo-controlled, double-blind, crossover study. Of the 5 endothelial dysfunction biomarkers measured, soluble endothelial selectin was significantly reduced (P = 0.03) by epicatechin and quercetin supplementation. No other biomarkers were significantly affected by epicatechin; however, pure quercetin supplementation also reduced inflammatory markers (ie, IL-1-beta [P = 0.009], z score for inflammation [P = 0.02]). As a reference, it’s important to note that 4 cups of black tea contain about 19 mg of quercetin.(53)

The effects of quercetin supplementation on CRP (a strong predictor of cardiovascular disease) were assessed in a systematic review and subsequent meta-analysis of 7 double-blind, randomized, placebo-controlled trials (N=549), including 4 crossovers. The studies had sample sizes of 40 to 93 adult participants (1 study enrolled only males, 2 studies enrolled only females) and administered quercetin at dosages of 150 to 500 mg/day for 6 to 10 weeks. Baseline CRP levels ranged from 1.28 to 5.7 mg/L (mean, 3.44 mg/L) in patients with body mass indices of 21.4 to 31.1 kg/m² and who presented with a variety of conditions (eg, metabolic syndrome, pre-hypertension, mild hypertension, rheumatoid arthritis, type 2 diabetes, various apolipoprotein genotypes). Overall, data showed a statistically significant reduction in CRP (weight mean difference, −0.33 mg/L; P<0.001) in favor of quercetin. The effect size was robust; however, study heterogeneity was significant. Subgroup analysis revealed baseline CRP <3 mg/L, quercetin dose ≥500 mg, duration of treatment ≥8 weeks, mean age of participants ≤45 years, and a parallel study design to be variables that led to significant beneficial results of quercetin on CRP (P<0.001 to P=0.002).(54)

Exercise/Performance

Animal data

Studies in mice have shown efficacy of quercetin supplementation in enhancing physical activity; however, the relevance of data from animal studies is diminished by the availability of clinical trial data and a published meta-analysis.(32, 33)

Clinical data

A meta-analysis, which included 11 clinical trials conducted through July 2010, found that quercetin supplementation marginally improved physical endurance capacity by approximately 3%. Median treatment duration was 11 days, using a median dose of quercetin 1,000 mg per day.(32) Improvement in endurance performance was additionally documented in a meta-analysis of 7 trials identified between 1966 and March, 2011. A significant improvement of 0.74% (P = 0.02) in endurance performance was noted; however, this result was influenced mostly by the positive effect attained in untrained subjects (0.83%) versus trained participants (0.09%). VO₂max was also significantly increased (P = 0.02). No heterogeneity was noted among studies.(51)

Iron overload

Clinical data

Limited data from 71 patients with beta-thalassemia major enrolled in a double-blind, randomized, placebo-controlled trial showed that administration of 500 mg/day quercetin with standard chelation therapy significantly reduced serum iron (P=0.036) and ferritin (P=0.043) after 12 weeks compared to placebo. Transferrin, transferrin saturation, and high-sensitivity C-reactive protein were also significantly improved with quercetin administration (P=0.045, P=0.008, P=0.046, respectively).(55)

Nervous system

Studies suggestive of a neuroprotective role have been conducted in human and animal nervous system tissues and in vitro in animals.(36) Clinical studies are lacking, except for a preliminary report on the role of quercetin in peripheral neuropathy due to diabetes, which found improvements in symptoms.(37)

Dosing

Typical dietary quercetin intake based on fruit and vegetable consumption is estimated to be from 5 to 100 mg per day. Heavy consumption of foods rich in quercetin, such as apples or onions, could lead to daily intakes of up to 500 mg.1, 5, 7, 15 The effective dose is increased when eaten with a fatty meal or in the presence of apple pectin, oligosaccharides, and lecithin.3, 5

Most clinical studies use quercetin 500 to 1,000 mg per day in divided doses.1, 14, 32

As a dietary supplement, 2 weeks of quercetin 50 mg achieved a 178% increase in serum levels, while quercetin 100 mg increased the levels by 359%, and quercetin 500 mg increased serum levels by 570%, although with wide individual variation.38 Based on animal studies, quercetin accumulates in the lungs, liver, kidneys, and small intestine, with lower levels seen in the brain, heart, and spleen. It is eliminated via the renal, fecal, and respiratory systems.7, 9, 15, 39

Pregnancy / Lactation

GRAS when consumed as food. Avoid dosages above those found in foods because information regarding safety and efficacy in pregnancy and lactation is lacking for such doses. Fetal growth retardation was observed in a study in rats exposed to quercetin by oral gavage. No signs of embryonic viability or morphology were apparent.40

Interactions

Caffeine and caffeine-containing products: Quercetin may increase the serum concentration of caffeine and caffeine-containing products. No action needed.(44, 45)

Chlorzoxazone: CYP2E1 inhibitors (weak) may increase the serum concentration of chlorzoxazone. No action needed.(46, 48, 49)

Cyclosporine (systemic): Quercetin may increase the serum concentration of cyclosporine (systemic). Monitor therapy.(43)

Diclofenac (systemic): Quercetin may increase the serum concentration of diclofenac (systemic). Monitor therapy.(57)

Fexofenadine: Quercetin may increase the serum concentration of fexofenadine. No action needed.(42)

Fosphenytoin-phenytoin: CYP2C9 inhibitors (weak) may increase the serum concentration of fosphenytoin-phenytoin. Monitor therapy.(58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77)

Midazolam: Quercetin may decrease the serum concentration of midazolam. No action needed.(41, 78, 79, 80)

Pravastatin: Quercetin may increase the serum concentration of pravastatin. No action needed.(81)

Tolbutamide: CYP2C9 inhibitors (weak) may increase the serum concentration of tolbutamide. Monitor therapy.(82, 83, 84, 85, 86)

Vitamin K antagonists: CYP2C9 inhibitors (weak) may increase the serum concentration of vitamin K antagonists. Monitor therapy.(52, 87, 88, 89, 90, 91, 92, 93, 94)

Adverse Reactions

At oral supplemental doses of up to 1,000 mg/day, taken for up to 12 weeks, no evidence of toxicity or clinically important adverse effects have been found; however, data on long-term safety at high doses are lacking.5, 7 Clinical studies report no clinically important adverse effects.14, 27

Related/similar drugs

Toxicology

Quercetin shows in vitro mutagenicity in the Ames test, and reports of mutagenicity in the 1970s led to concerns about its safety.5, 7 Under certain circumstances, quercetin exhibits both radical scavenging and pro-oxidant activity.1, 5 In 1999, however, the International Agency for Research on Cancer classified quercetin as "not classifiable as to its carcinogenicity" to humans.5, 40 Most in vivo studies have shown that quercetin is not carcinogenic and may be protective against genotoxicants.1

Dietary quercetin undergoes first-pass metabolism in the gut and liver and is almost completely metabolized, reducing the potential for toxicity. At oral supplemental doses of up to 1,000 mg per day taken for up to 12 weeks, no evidence of toxicity has been found; however, data on long-term safety at high doses are lacking.5, 7 Nephrotoxicity was reported with the use of high-dose IV quercetin in a patient with compromised health.5, 15

References

Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

Frequently asked questions

• What is Quercetin and what are its health benefits?
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