- An antioxidant flavonoid
- Helps stabilize mast cells that store and release histamine and other active compounds
- Provides support for patients who suffer from allergies
- Provides support for patients who suffer mast cell activation dysregulation
- May offer benefit in reducing risk of severe COVID-19 complications
Quercetin has many beneficial effects on human health. Perhaps its best-known benefit comes from the stabilization of mast cell membranes which helps decrease the release of histamine and other compounds that interact with other cells to impact inflammation and other conditions. A number of quercetin’s beneficial effects appear to be due to its antioxidant activity. Quercetin scavenges free radicals and inhibits the oxidation of LDL cholesterol. Quercetin, especially when paired with vitamin C, reduces oxidative damage to skin and nerves caused by glutathione depletion. Other benefits include cardiovascular support and protection of the gastrointestinal tract.
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Widely distributed in the plant kingdom, quercetin is a flavonoid compound found in many plants and foods. Flavonoids are a group of compounds that help regulate cellular activity and through their antioxidant effects fight off free radicals that cause oxidative stress. In simpler terms, they help the body function more efficiently while protecting it against everyday toxins and stressors.
Quercetin is the most abundant and most studied flavonoids (subgroup, flavonols) and is found in many foods. Onions are the most important sources of quercetin, but other vegetables including broccoli, asparagus, green peppers, tomatoes and red leaf lettuce, are great sources of quercetin, especially in the summer. Apples, strawberry, red raspberry, blueberry, cranberry and black currants, teas and wine are also considered abundant dietary sources of quercetin. While generally found at relatively low concentrations of 15–30 mg/kg (fresh weight), some vegetables such as onions and shallots have much more extensive content.
Black tea and oolong tea, both fermented tea types, have the highest content of quercetin types of flavonol glycosides (50%–52% in oolong tea and 54%–71% in black tea, respectively); green tea manufactured without the process of fermentation has a higher content of kaempferol glycosides, while quercetin represents about 18%–38% of all flavonol glycosides.
Quercetin has many beneficial effects on human health that include antiviral properties, cardiovascular support and protection of the gastrointestinal tract. Quercetin also stabilizes mast cells and may reduce the inflammation associated with severe infection. The benefits of quercetin can be enhanced by the co-administration of vitamin C.
Quercetin has a broad range of antiviral properties which can potentially interfere at multiple steps with viral infection including suppression of virus entry into cells, virus replication aand viral protein assembly. It stimulates the immune system and its broad range of antiviral properties has been suggested to potentially interfere with COVID-19 infection. Quercetin also targets viral polymerases and may disrupt replication via the inhibition of reverse transcriptase enzymes.
Anti-inflammatory and Anti-allergic Properties
Quercetin has strong anti-allergic properties through its inhibition of histamine production and release by mast cells. It has also been shown to suppress activation of NLRP3 inflammasome to reduce the inflammatory process. In addition, quercetin up-regulates the NF- B and Nrf2 pathways that stimulate intracellular productiom of antioxidants. (see NRF2 Activators).
A number of quercetin’s beneficial effects are due to its antioxidant activity. Quercetin scavenges free radicals and inhibits the oxidation of LDL cholesterol. Quercetin, especially when paired with vitamin C, reduces the incidence of oxidative damage to skin and nerves caused by glutathione depletion.
Mast Cell Stabilization
Probably the most well-known of quercetin’s mechanisms of action involves stabilization of mast cell membranes. Mast cells function as sentinels or guards that are able to sense a wide range of potential injury to the body such as infections or environmental toxins. When a mast cell senses a threat, it “activates,” producing and releasing chemical “mediators” directed at assisting the body in managing the threat. These mediators include histamine, pro-inflammatory cytokines, leukotrienes, and interleukin IL-4. They are primary players in allergic reactions and the inflammatory responses to injury and infection.
In some cases, however, mast cell activation becomes dysregulated and the excessive or inappropriate release of mediators, especially histamine and pro-inflammatory cytokines, can lead to a wide range of symptoms and disease processes.
Inappropriate mast cell activation is linked to certain cancers, cardiovascular diseases, connective tissue disorders, allergy, asthma and irritable bowel syndrome (IBS). Mast cell dysregulation can drive seasonal allergies and auto-immune conditions such as rheumatoid arthritis (RA) and Lupus. Mast cells and inflammation of the brain have been linked to depression, anxiety and other mental health conditions. They may also be linked to Ehler Danlos Syndrome, autonomic dysfunction (dysautonomia) celiac disease and Interstitial Cystitis (IC).
Mast Cell Activation Disease (MCAD) is an umbrella term that includes a collection of disorders characterized by (1) accumulation of genetically altered or dysregulated mast cells and/or (2) abnormal release of these cells’ mediators, including Mast Cell Activation Syndrome (MCAS). MCAS is a chronic multisystem disorder with inflammatory and allergic manifestations and is fairly common, with an estimated prevalence of 17% of the general population. MCAS is thought to be involved in the etiology of many medical conditions including idiopathic anaphylaxis, interstitial cystitis, some subsets of fibromyalgia and irritable bowel syndrome, as well as neurologic and psychiatric symptoms and diseases.
Quercetin stabilizes mast cells and suppresses mast cell activity including the creation of leukotrienes, suppression of interleukin IL-4 production and inhibition of histamine and pro-inflammatory cytokines release. Evidence suggests that quercetin may have therapeutic benefit in the treatment of MCAS and related conditions characterized by mast cell dysregulation.
Quercetin Synergy with Vitamin C
Quercetin’s therapeutic benefits can be enhanced by the co-administration of vitamin C. Vitamin C prevents the spontaneous degradation of quercetin and it also has the capacity to recycle quercetin, increasing its efficacy. Vitamin C and quercetin co-administration also exerts a synergistic antiviral action due to overlapping antiviral and immunomodulatory properties.
Vitamin C has a supportive role in the prevention and treatment of colds and viral inections. Quercetin and ascorbic acid co-administration is a strategy with current evidence supporting their use for prophylaxis and treatment of several respiratory viruses, including SARS-CoV-2 (COVID-19). Vitamin C and quercetin co-administration exerts a synergistic antiviral action due to overlapping antiviral and immunomodulatory properties. The blockage of virus entry represents a key strategy and quercetin impedes viral membrane fusion for both influenza and SARS-Cov.
Both quercetin and vitamin C have excellent safety profiles with a favorable risk to benefit ratio. Furthermore, based on their lack of severe side effects and low-costs, the combined administration of these two compounds for both the prophylaxis and the early treatment of respiratory tract infections, especially including COVID-19.
Quercetin Synergy with Zinc
Quercetin also chelates, or binds, to zinc and transports it into cells which could, theoretically, enhance the anti-viral actions of zinc.
Dietary quercetin has poor water solubility, chemical instability, and low oral bioavailability. Additionally, quercetin is digested (e.g., mouth, small intestine, liver, kidneys) it undergoes glucuronidation, sulfation, or methylation that further reduces its bioavailability. To overcome these issues, different formulations have been engaged to improve its stability, efficacy, and bioavailability. These formulations include phytosomal and nanoformulations, lipid-based carriers, micelles, metallic nanoparticles, inclusion complexes, and conjugate-based encapsulation.
Phytosome Formulations of Quercetin
Phytosome complexes are created by a process that binds quercetin to a botanical extract of phosphatidylcholine, a key component of cell membranes. Phytosome complexes enhance the absorption of quercetin from the gut.
Nanformulations of Quercetin
Drug Interactions with Quercetin
While the clinical significance has not yet been established, Quercetin has been shown to inhibit P-gp, a transporter that affects blood levels and central nervous system levels of certain drugs. As a result of this inhibition, it may be possible that Quercetin can decrease blood levels but at the same time increase central nervous levels of fentanyl, morphine, methadone and possibly oxycodone. This could result in either increased or decreased therapeutic effect and/or side effects. When taking Quercetin while also taking these medications, caution should be emphasized by monitoring for changes in responsiveness to the medications and it may be necessary to reduce the dose of these medications to avoid side effects.
Quercetin – Overviews
- Quercetin | University of Maryland Medical Center
- Quercetin Attenuates Inflammatory Responses in BV-2 Microglial Cells
- Quercetin and derivatives: useful tools in inflammation and pain management. – PubMed – NCBI
Quercetin – COVID-19
- Quercetin and Vitamin C – An Experimental, Synergistic Therapy for the Prevention and Treatment of SARS-CoV-2 Related Disease (COVID-19) – 2020
- Quercetin Is More Effective than Cromolyn in Blocking Human Mast Cell Cytokine Release and Inhibits Contact Dermatitis and Photosensitivity in Humans – 2012
- Quercetin Inhibits the Production of IL-1β-Induced Inflammatory Cytokines and Chemokines in ARPE-19 Cells via the MAPK and NF-κB Signaling Pathways – 2020
- Quercetin and Its Anti-Allergic Immune Response – 2016
Quercetin – COMT inhibitor
- Phytochemicals Inhibit Catechol-O-Methyltransferase Activity in Cytosolic Fractions from Healthy Human Mammary Tissues – Implications for Catechol Estrogen-Induced DNA Damage – 2004
Quercetin – Drug Interactions
- Overview of P-glycoprotein inhibitors – a rational outlook – 2012
- Emerging Significance of Flavonoids as P-Glycoprotein Inhibitors in Cancer Chemotherapy – 2009
- Herbal modulation of P-glycoprotein. [Drug Metab Rev. 2004] – PubMed – NCBI
Quercitin – Green tea
- Quercetin increased bioavailability and decreased methylation of green tea polyphenols in vitro and in vivo
Quercetin – Liver Disease
Quercetin – Nanoformulations
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