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    Features

    Quercetin in the Antioxidant Spotlight

    This flavonol has been used for allergies, heart health, prostate issues, and more.

    Quercetin in the Antioxidant Spotlight
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    By Sean Moloughney, Editor03.02.22
    Found in apples, berries, onions, tea, and grapes, among other plants, quercetin has been shown to exhibit antioxidant, anti-inflammatory, and immunomodulatory activity. This flavonol has been commonly used against allergies and for cardiovascular health and prostate support.

    According to SPINS data curated and published by HerbalGram, sales of quercetin in the natural retail channel totaled $6.4 million in 2020, a 74.1% increase from 2019. Quercetin supplements for cardiovascular health and prostate support in particular experienced significant overall sales increases of 233% and 132%, respectively, in 2020, according to HerbalGram. Quercetin supplements marketed for immune health, which make up a minority of quercetin supplement sales, also saw a sales increase of 59% in 2020.

    According to the Council for Responsible Nutrition’s consumer survey, cardiovascular health ranked behind overall health/wellness and immune health as the most-cited reasons why dietary supplement users purchased such products in 2020.

    HerbalGram noted at least two scientific reviews published in 2020 that focused on the potential cardiovascular benefits of quercetin. In one review of 17 human clinical trials, the authors concluded that quercetin supplementation was associated with significant reductions in systolic and diastolic blood pressure; and in a subgroup analysis of those who consumed quercetin for more than eight weeks, quercetin was associated with significantly improved levels of HDL cholesterol and triglycerides.

    A separate review of 16 human clinical trials on quercetin supplementation in patients with metabolic syndrome and related conditions concluded that quercetin was associated with reduced levels of total cholesterol, LDL cholesterol, and the inflammatory marker C-reactive protein.

    “Quercetin is categorized as a flavonol, one of the six subclasses of flavonoid compounds,” noted Greg Ris, vice president of sales, Indena USA, Inc. “Among flavonol molecules, quercetin is the most abundant in fruits and vegetables, where it is contained in the form of glycosides in which quercetin is linked to a sugar moiety; D-glucose is the most frequent sugar residue (quercetin glucosides), but others are found as well.”

    In terms of antioxidant potential, quercetin is one of the most potent flavonoids for protecting the body against free radicals such as ROS and RNS, said Ris. Its antioxidant activity can be carried out through different mechanisms of action1-4 including:

    • Direct inactivation of free radicals, thanks to its chemical structure and electron-donating activity;
    • Inhibition of enzymes such as NO-synthase (responsible for NO synthesis) and xanthine oxidase (involved in metabolism of uric acid);
    • Inhibition of lipid peroxidation, which can block the oxidative stress cascade from the beginning;
    • Inhibition of LDL-oxidation, responsible for atherosclerotic plaques, leading to cardiovascular disease;
    • Improved synthesis of glutathione, an endogenous antioxidant; and
    • Chelation of ions (e.g., calcium and iron), which can initiate synthesis of reactive species.
    Quercetin has also shown to be a modulator of inflammatory response with strong anti-inflammatory capacities5-7 including: modulation of NF-kB transcription factor; inhibition of cytochines (e.g., TNF-α); and inhibition of production of pro-inflammatory enzymes, such as cyclooxygenase (COX) and lipoxygenase (LOX), which catalyze the conversion of arachidonic acid to its metabolites.

    “These anti-inflammatory effects of quercetin are related to its strong antioxidant activity,” said Ris, “and may be found in the interplay between oxidative stress and inflammation; however, at the same time, oxidation and inflammation are closely related to physiological immune response.”

    Quercetin can play an important role in modulating immunity as well through several specific actions8-9 such as:

    • Stabilization of cell membranes acting as calmodulin antagonism, preventing release of allergic mediators and substances;
    • Reduction of histamine secretion from mast cells and basophils; 
    • Reduction of release of cytokines (e.g., TNF-α) and interleukins from mast cells and basophils;
    • Inhibition of antibodies IgE, responsible for allergic symptoms causing release of chemicals determining allergic reactions in the nose, lung, throat, and skin;
    • Inhibition of enzymes cyclooxygenase and lipoxygenase, leading to reduction of thromboxane, prostaglandins and leukotrienes involved in immune reactions;
    • Immune response regulation by targeting enzymes in white blood cells, such as kinases and phosphatases essential for cellular immune response;
    • Immuno-stimulatory effect by inducing gene expression for release of interferon-γ (IFN-γ) and stimulating of immune cells, such as lymphocytes.
    Despite being so common in fruits and vegetables, daily intake of quercetin can vary due to differences among people, their dietary habits, and the intrinsic low bioavailability of the quercetin molecule, said Ris. “These drawbacks hamper quercetin from addressing biological targets and achieving health benefits.”

    However, Indena’s Quercefit Quercetin Phytosome is a standardized and bioavailable form of quercetin that is formulated with the company’s Phytosome technology to overcome its poor oral bioavailability.

    “A published human pharmacokinetic study10 demonstrates optimized quercetin plasma levels after a single administration of Quercefit compared with unformulated quercetin,” said Ris. “This leads Quercefit to be effective in conditions characterized by intense oxidative stress, inflammation and/or immune response as demonstrated in human studies.”

    Specifically, a human study on supplementary management of respiratory discomfort during allergy seasons showed the benefits of Quercefit in reducing day (-50%) and night (-70%) intermittent symptom frequency and a significant improvement of breath function (Peak Expiratory Flow) in mild, persistent discomfort. “The supplementary use of Quercefit synergistically improved the use of the best available remedy,” said Ris, “while optimizing additional discomfort conditions and keeping a low oxidative stress with a very good safety profile.”11

    References
    1. Rice-evans, C. et al. “The relative antioxidant activities of plant-derived polyphenolic flavonoids.” Free radical research 22.4 (1995): 375-383.
    2. Lakhanpal, P. et al. “Quercetin: a versatile flavonoid.” Internet Journal of Medical Update 2.2 (2007): 22-37.
    3. Meyer, A. et al. “Antioxidant interactions of catechin, cyanidin, caffeic acid, quercetin, and ellagic acid on human LDL oxidation.” Food Chemistry 61.1-2 (1998): 71-75.
    4. Xu, D. et al. “Antioxidant activities of quercetin and its complexes for medicinal application.” Molecules 24.6 (2019): 1123.
    5. Li, Y. et al. “Quercetin, inflammation and immunity.” Nutrients 8.3 (2016): 167.
    6. Boots, A. et al. “Health effects of quercetin: from antioxidant to nutraceutical.” European journal of pharmacology 585.2-3 (2008): 325-337.
    7. Liu, C.M. et al. “Protective role of quercetin against lead-induced inflammatory response in rat kidney through the ROS-mediated MAPKs and NF-κB pathway.” Biochimica et Biophysica Acta (BBA)-General Subjects 1820.10 (2012):1693-1703.
    8. Mlcek, J. et al. “Quercetin and its anti-allergic immune response.” Molecules 21.5 (2016): 623.
    9. Fortunato, L.R. et al. “Quercetin: a flavonoid with the potential to treat asthma.” Brazilian journal of pharmaceutical sciences 48.4 (2012):
    10. 589-599.
    11. Riva, A. et al. “Improved oral absorption of quercetin from Quercetin Phytosome®, a new delivery system based on food grade lecithin.” European journal of drug metabolism and pharmacokinetics 44.2 (2019): 169-177.
    12. Cesarone, M. et al. “Supplementary prevention and management of asthma with quercetin phytosome: a pilot registry.” Minerva medica (2019). 
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