James Odell, OMD, ND, L.Ac.

Quercetin (3,3',4',5,7-pentahydroxyflavone) is a flavonoid, or more specifically a subclass called flavanol, and is widely distributed in the plant kingdom. Its name is from the Latin quercetum (oak forest) after quercus (oak) from which quercetin was first isolated. Quercetin has been extensively studied by researchers over the past 40 years. Bioflavonoids were first discovered by Nobel Prize laureate Albert Szent Gyorgyi in the year 1930. All flavonoids are plant metabolites that share a structural similarity based on three phenol ring basic structures with hydroxyl (OH) groups attached. They are found in leaves, flowers, roots, seeds, nuts, and barks of numerous plants across the earth. Flavonoids fulfill many biological functions including UV protection, pigmentation, and antimicrobial defense. Quercetin has been widely investigated and found to have numerous health benefits ranging from prevention to treatment of many diseases.

Quercetin flavanol is characterized by 4 unique properties: antioxidant, anti-inflammatory, anti-allergy, and neuroprotection. The combination of these 4 properties makes quercetin an excellent candidate for dealing with situations in which oxidative stress, inflammation, and the neuroimmune system are involved. Quercetin also possesses antimicrobial and anti-cancerous properties and is protective of the cardiovascular and reproductive systems. Numerous studies have shown the ability of quercetin to enhance the efficacy of some types of chemotherapy and ameliorate its toxic side effects.1

More recently quercetin has been demonstrated to be a zinc ionophore which allows zinc to better pass-through cell membranes. Thus, quercetin is useful in tandem with zinc for improving immunity, as zinc is very important for many immunological enzymes. One major barrier to zinc treatment is that zinc has a hard time passing through the cell’s membrane which is made of fat. Fortunately, some molecules, like quercetin, can act as facilitators and enhance the entry of zinc into the cell. Dietary plant polyphenols such as the flavonoids quercetin and epigallocatechin-gallate (EGCG – green tea extract) both act as antioxidants and are excellent ionophores of zinc. Remarkably, the activities of numerous enzymes that are targeted by polyphenols are dependent on zinc. Thus, these polyphenols chelate zinc cations, and act as zinc ionophores, transporting zinc cations through the plasma membrane.

Interestingly, quercetin levels in plants positively correlated with exposure to UVB radiation, and its accumulation have been considered natural protection against UV-induced damage.2

Antioxidant Properties

Oxidative free radicals or reactive oxygen species (ROS) are generated within the cells during normal metabolic processes but are also induced from toxic environmental sources including tobacco smoke, air pollutants, and radiation, among others. Elevated levels of ROS in the cells result in oxidative stress which has been associated with the etiology of various degenerative diseases. The most characteristic feature of quercetin is its potent ROS scavenging capability.3 Flavonoids are generally antioxidants, and several of quercetin’s bio-regulating effects appear to be attributed to its antioxidant activity.4, 5, 6, 7

Quercetin’s anti-oxidative properties result from its chemical structure that allows for direct neutralization of free radicals. Its plasma metabolites such as quercetin-3-O-β-D-glucuronide have radical scavenging properties inhibiting low-density lipoprotein (LDL cholesterol) oxidation as well as protecting erythrocytes (red blood cells) from damage caused by smoking.8, 9

As another indicator of its antioxidant effects, quercetin inhibits the oxidation of LDL cholesterol in vitro,10, 11 probably by inhibiting LDL oxidation itself, by protecting vitamin E in LDL from being oxidized, or by regenerating oxidized vitamin E.12

By itself, and paired with ascorbic acid (vitamin C), quercetin has been shown to reduce the incidence of oxidative damage to human lymphocytes and neurovascular structures in the skin and inhibit damage to neurons caused by experimental glutathione depletion.13, 14

Quercetin can also activate cellular antioxidant systems by increasing both transcriptional and post-transcriptional levels of Nrf-2, a transcription factor that induces the expression of various antioxidant and phase-II detoxifying enzymes including NAD(P)H quinone oxidoreductase 1 (Nqo1), glutamate-cysteine ligase (GCL), heme oxygenase-1 (HO-1), and many others. At the same time, quercetin reduces the level of Keap1 (that keeps Nrf-2 in the cytoplasm and thus blocks its activity) through the modification of Keap1 protein rather than 26S proteasome degradation.15

Anti-inflammatory Properties

Due to its powerful antioxidant properties, quercetin can aid in fighting inflammatory problems because free radicals are involved in cellular mechanisms generating pro-inflammatory cytokines.16 Quercetin also inhibits the formation of inflammatory prostaglandins and leukotrienes, as well as histamine release. This may be especially helpful in asthma, as leukotriene B4 is a potent bronchoconstrictor. Patients suffering from chronic inflammatory conditions such as chronic prostatitis and interstitial cystitis show significant symptomatic improvement with oral quercetin supplementation (500 mg BID for one month).17, 18

Unlike classic non-steroidal anti-inflammatory drugs (NSAIDs) that reduce inflammation at the enzymatic level by blocking cyclooxygenase (COX) enzymes involved in the production of inflammatory mediators (e.g., prostaglandins), quercetin acts in a more sophisticated manner interfering with COX gene expression. It also inhibits the activity of the cellular protein complex called nuclear factor kappa B (NFkB) which, upon activation, translocates to the nucleus and initiates the expression of many pro-inflammatory molecules such as tumor necrosis factor-alpha (TNF-α) and COX enzymes.19

In addition, quercetin can directly inhibit another group of enzymes called lipoxygenases thereby reducing the production of leukotrienes which play a critical role in asthma.20

Anti-Allergy and Asthma Properties

In addition to being an antioxidant and anti-inflammatory quercetin’s benefits have been well recognized in allergy relief and asthma. Sneezing, runny nose, watery eyes, itchy eyes, and skin irritations are the results of histamine release from immune cells known as mast cells or basophils (types of white blood cells). In vitro quercetin inhibits histamine release by mast cells and basophils, promoting an anti-allergy effect. 21, 22

Animal evidence indicates that quercetin might have therapeutic potential for allergic airway disease. Several studies conducted in guinea pigs have reported that quercetin, provided orally or administered via inhalation, has anti-asthmatic activity.23, 24, 25

In murine models of allergic airway inflammation and asthma, quercetin had pronounced anti-inflammatory effects26, reduced eosinophil and neutrophil counts and infiltration in lung tissue27 and inhibited asthmatic reactions.28

Also, results from human studies have shown beneficial effects of quercetin supplementation on allergy symptoms due to pollen exposure.29, 30

Quercetin’s mast cell-stabilizing effects make it a suitable supplement for use in preventing histamine release in allergy cases, like the use of the synthetic flavonoid analog cromolyn sodium. Another study demonstrated quercetin to be more effective than the drug cromolyn against contact dermatitis and photosensitivity which are types of skin allergies.31 In the same study, researchers found that for cromolyn to be effective it must be added at the same time as the trigger, while quercetin can be used prophylactically.

Prophylactic supplementation of quercetin may also be beneficial in the control of food allergies. According to research data, quercetin was found to block intestinal allergic inflammation in vitro.32 Very promising findings came from an animal study in which quercetin completely attenuated life-threatening anaphylactic response to peanuts in peanut-allergic rats.33 Considering that peanut allergy in humans is one of the most frequent and dangerous food allergies and that the anaphylactic reaction is often fatal, the authors propounded the use of quercetin as an alternative approach against immunoglobulin E-mediated food allergies.


Several studies in vitro, in experimental animals, and humans, have provided supportive evidence for the neuroprotective effects of quercetin, either against neurotoxic chemicals or in various models of neuronal injury and neurodegenerative diseases. The exact mechanisms of such protective effects remain elusive, though many hypotheses have been formulated. In addition to a possible direct antioxidant effect, quercetin may also act by stimulating cellular defenses against oxidative stress.

In vitro studies in neuronal cell lines and primary neurons have shown that quercetin, at low micromolar concentrations, antagonizes cell toxicity induced by various oxidants (e.g., hydrogen peroxide, linoleic acid hydroperoxide) and other neurotoxic molecules believed to act by inducing oxidative stress.34, 35, 36, 37, 38

Several studies show that quercetin can exert neuroprotection and antagonize oxidative stress when administered in vivo. For example, oral quercetin (0.5–50 mg/kg) was shown to protect rodents from oxidative stress and neurotoxicity induced by various neurotoxic insults.39, 40

Concerning metal toxicity, quercetin has been shown to protect against the neurotoxicity of lead, methylmercury, and tungsten. 41, 42, 43

The neurotoxicity of polychlorinated biphenyls, the insecticide endosulfan, and MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) has also been shown to be reduced by quercetin in vivo. 44, 45, 46

In rats, post-trauma administration of quercetin improves recovery of motor function after acute traumatic spinal cord injury. Intraperitoneal doses of 5-100 micromoles quercetin/kg body weight resulted in half or more of the animals walking, although with a deficit.47 This ability to promote recovery from spinal cord injury appears to be highly dependent on the dose and frequency of dosing. In this study a lower intraperitoneal dose was ineffective.

As previously discussed, quercetin exhibits anti-inflammatory properties. Neuroinflammation is emerging as playing a most relevant role in neurodevelopmental and neurodegenerative disorders and thus represents a potentially important target for therapeutic interventions.48, 49 Thus, compounds that may antagonize microglia activation and reduce the release of proinflammatory cytokines would be of great benefit. Quercetin has been shown to reduce lipopolysaccharide-induced nitric oxide release from a mouse neuroglia cell line.50, 51

The ability of quercetin to counteract oxidative stress-mediated neurotoxicity opens new perspectives in research and clinical applications of quercetin. Several neurological disorders including Parkinson's disease, Alzheimer's disease, and depression have been associated with neurodegeneration induced by free radicals.

Quercetin Food Sources

Quercetin-type flavonols (primarily quercetin glycosides), the most abundant of the flavonoid molecules, are widely distributed in the plant kingdom. They are found in a variety of foods including apples, berries, Brassica vegetables, capers, grapes, onions, shallots, tea, and tomatoes, as well as many seeds, nuts, flowers, barks, and leaves. Quercetin is also found in medicinal botanicals, including Ginkgo biloba, Hypericum perforatum (St. John’s wort), and Sambucus canadensis (elder).52, 53, 54

Quercetin Side Effects and Toxicity Data

In human studies, quercetin has generally been well tolerated. Doses up to 1,000 mg/day for several months have produced no adverse effects on blood parameters of liver and kidney function, hematology, or serum electrolytes.


A typical dose is 250 mg, two to three times per day. Quercetin’s beneficial health effects are potentiated in synergy with vitamin C, resveratrol, curcumin, EGCG (epigallocatechin gallate), and many other nutraceuticals. Since solubility is an issue in quercetin absorption, a new, water-soluble quercetin molecule, quercetin chalcone, might be used in smaller doses.55


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