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    What is Quercetin? Benefits, Dosage, and Risks

    What is Quercetin? Benefits, Dosage, and Risks
    January 28, 2022 Vitality Pro

    What is Quercetin? Benefits, Dosage, and Risks

    What is Quercetin?

    Quercetin is a powerful plant compound found in a variety of foods ranging from leafy greens to fruits and teas. It is classified as a flavonoid, which is a broad sub-class of polyphenols (plant chemicals) that are known to deliver various health benefits from decades of cell, animal, and human research.

    Quercetin is one of the most studied flavonoids in the field of longevity research. In fact, a quick search for this well-known plant compound on the National Library of Medicine website returns over 2,300 results. Of those results, 30 are clinical trials.

    Many foods are rich in this potent anti-aging compound, including berries, citrus fruits, leafy greens, and even red wine.

    For individuals interested in supplementing their diet with high doses of quercetin, a variety of products are available. And as a supplement, the U.S. Food and Drug Administration has labeled quercetin a “Generally Recognized as Safe” (GRAS) ingredient.

    Despite being a plant compound and having a GRAS label from the FDA, several studies indicate quercetin may be harmful to certain individuals.

    Those who suffer with kidney issues, and especially those who take medications known to cause kidney damage, are particularly at risk.

    Quercetin is also thought to have adverse effects when combined with dozens of different prescription medications, including medicines for hypertension, diabetes, blood thinners, antipsychotics, and more (see Potential Health Risks and Side Effects below).

    Quercetin is believed to have 3 key mechanisms of action. These include functioning as an antioxidant, anti-inflammatory, and anti-viral compound.

    Some studies suggest quercetin may also be a senolytic compound, but additional research is needed to validate such claims.

    Overview of Potential Benefits and Risk

    Disclaimer: Always consult your health care professional prior to making changes in your diet or exercise regimen, including whether to use supplements like quercetin. Pregnant women, women who are nursing, and children especially must always consult a physician prior to taking supplements or medications.

    Overview of potential Quercetin health benefits:

    • Cellular Protection from Oxidative Stress
    • Reduced Inflammation
    • Reduced Symptoms of Metabolic Syndrome
    • Obesity Prevention
    • Type 2 Diabetes Prevention
    • Improved Brain Health and Memory
    • Improved Mood
    • Reduced Risk of Cancer
    • Allergy Relief

    Overview of potential risks and side effects:

    • Risk of Exacerbated Kidney Damage
    • Risk of Adverse Reactions with Prescription Medications

    How Does Quercetin Work?

    Polyphenols represent a large and diverse class of plant compounds that have played a key role in human evolution for thousands of years. Within that class lies a potent sub-class of phytochemicals called flavonoids.

    After decades of research, a growing body of evidence indicates flavonoids have an anti-oxidative, anti-inflammatory, and anti-carcinogenic effect at the cellular level. Studies indicate at least 4 potential mechanisms of action for this anti-aging compound, including:

    • Reducing oxidative stress
    • Reducing inflammation and related diseases
    • Functioning as an antiviral agent
    • Potentially functioning as a senolytic

    Reducing oxidative stress

    Like many flavonoids, quercetin demonstrates great efficacy as an antioxidant. This appears to be one of the primary mechanisms of action driving the plant compound’s ability to promote cellular health and longevity.

    Antioxidants perform several functions, but the one most often linked to longevity is their ability to reduce oxidative stress. Quercetin’s unique chemical structure makes it a potent antioxidant capable of doing just that.

    In a 2019 article published by the journal Molecules, researchers illustrated quercetin’s ability to neutralize free radicals as they were produced by mitochondria, the powerhouses that create energy within each cell.

    They explain that quercetin also appears to promote the body’s natural antioxidant system by interacting with NFRB, AMPK, and MAPK signalling pathways within the cell.

    Quercetin has also been shown in both animal and cell studies to promote synthesis of glutathione, a vital antioxidant that is produced in the body as a line of defense against free radical damage.

    This vital antioxidant is endogenous (meaning it is produced internally) and plays a critical role in tissue detoxification, reducing oxidative stress, and regulating immune system and healthy cell development.

    However, one in vitro cell study indicates quercetin can actually degrade into a free radical called semiquinone. This study also indicates cardiovascular exercise may worsen degradation and cause tissue and DNA damage.

    To date, researchers disagree on whether supplementing with high doses of quercetin delivers a net positive or negative result.

    Anyone interested in supplementing with quercetin should consult a physician, stay up to date on the latest research, and read more in the Quercetin Dosages and Supplementation section below.

    Reducing inflammation and related disease

    Many studies correlate inflammation with aging and age-related disease. In fact, a 2014 article published by The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences coined the term ‘Inflamm-aging’ to underscore the importance of this phenomenon and identify the core biological systems involved.

    Longevity research has identified several of these systems, and quercetin appears to have a beneficial impact on at least three of them: NF-κB, MAKP, and immune system cytokines.

    NF-κB and MAKB are two vital cellular signaling pathways. The first is known to induce inflammation in response to environmental stress, while the second is a protein network that facilitates communication within cells. Quercetin seems to suppress each, thereby reducing the onset and spread of inflammation.

    Inflammation is also mediated by the immune system through the use of unique proteins called cytokines. Some cytokines are pro-inflammatory, while others are anti-inflammatory.

    Research shows that pro-inflammatory cytokines can make disease and infection worse, while anti-inflammatory cytokines can attenuate symptoms.

    Remarkably, quercetin has been shown to decrease pro-inflammatory cytokines while simultaneously increasing the anti-inflammatory cytokines associated with healing.

    Functioning as an antiviral agent

    Various studies indicate quercetin has potential anti-viral properties. In a collative paper published by the peer-reviewed journal Frontiers in Immunology, researchers attribute quercetin’s anti-viral potential to its ability to suppress and/or prevent the following replication enzymes and activities within viral cells:

    • Polymerases
    • Proteases
    • Reverse transcriptase
    • DNA gyrase
    • Binding viral capsid proteins

    Each of the aforementioned processes play a role in viral replication and spread. For example, polymerase is an enzyme that is required to copy and assemble both DNA and RNA.

    This chain reaction is called Polymerase Chain Reaction, or PCR—an acronym widely used to describe the type of COVID-19 test that looks for signs of this reaction to identify the virus.

    Potentially functioning as a senolytic

    It is worth noting there is conflicting research on quercetin’s potential as a senolytic. Such compounds are believed to promote longevity by regulating healthy cellular aging and senescence.

    To date, the research is mixed. In 2018, a cell-based study indicated quercetin had zero impact on cellular senescence.

    In 2020, researchers found the direct opposite to be true. Many more studies offer inconclusive evidence, indicating the truth might be somewhere in the middle. Moving forward, it will be exciting to see if quercetin continues to show promise as a senolytic compound in human trials.

    What Foods Naturally Contain Quercetin?

    According to information published by the UC Cooperative Extension Center for Health and Nutrition Research at University of California Davis, the most potent food sources for quercetin include the following common fruits, vegetables, and drinks.

    Note: Quercetin content is expressed as total milligrams per 100 grams of food/drink:

    • Onions: 21.42mg
    • Kale: 7.71mg
    • Chives: 4.77mg
    • Pears: 4.51mg
    • Apples: 4.27mg
    • Cherry Tomatoes: 2.76mg
    • Cranberries: 2.76mg
    • Tea: 2.74mg*
    • White Currant: 2.68mg
    • Sweet Cherries: 2.64mg
    • Broccoli: 2.51mg
    • Apricots: 2.08mg
    • Red Grapes: 1.38mg
    • Fava Beans: 0.55mg
    • Leeks: 0.10mg

    *Specific variety of tea not mentioned in the publication referenced above. However, green and black teas are among the most studied varieties due to high concentrations of polyphenols.

    According to research published by the United States Department of Agriculture, brewed green and black teas contain about 2.69mg and 2.19mg of quercetin per 100 grams, respectively.

    In the same publication, the USDA also mentions that decaffeination and fermentation are not known to affect flavonoid levels.

    Quercetin Dosages and Supplementation

    Disclaimer: Always consult your health care professional prior to making changes in your diet or exercise regimen, including whether to use supplements like quercetin.

    Dosage

    Typical dosage ranges from 500mg to 1,000mg per day. Individual quercetin supplements may vary.

    Frequency

    Quercetin is generally considered safe in daily doses of up to 1,000mg for 12 weeks. However, usage data on higher concentrations and/or longer durations is not available.

    Frequency

    Quercetin is generally considered safe in daily doses of up to 1,000mg for 12 weeks. However, usage data on higher concentrations and/or longer durations is not available.

    Absorption

    Quercetin is characterized by relatively poor oral absorption. However, pairing quercetin with a food-based lecithin has been shown to increase absorption by a factor of 20. This is a common grouping in quercetin supplements, as is delivering quercetin in a liposomal (fat-based) matrix to improve absorption.

    Potential Health Benefits of Quercetin

    Quercetin is one of the most-studied flavonoids on the planet. Still, a majority of research conducted to date has utilized cell-based and animal models. For that reason, one should approach quercetin with caution.

    Many researchers are skeptical that health benefits observed in cell cultures can ever be replicated in humans.

    Disclaimer: Always consult your health care professional prior to making changes in your diet or exercise regimen, including whether to use supplements like quercetin.

    Prevention and Alleviation of Viral Infection

    As noted above, quercetin shows several key antiviral properties, like polymerase and protease inhibition. The same antiviral properties appear to make quercetin a promising tool in the fight against other kinds of viral infections.

    In a 2020 cell-based study, quercetin appeared to inhibit the spread of human herpesvirus. Another cell-based study indicates quercetin may also prevent the spread of hRSV, or human respiratory syncytial virus.

    This finding is particularly encouraging, as authors note hRSV is one of the most common respiratory infections driving hospitalizations among young children and the elderly.

    Cellular Protection from Oxidative Stress

    Just as fire produces smoke, cellular activity produces free radicals. These harmful molecules are inherently unstable and create a state of oxidative stress within the cells.

    Damage to lipids, proteins, and DNA are just a few consequences of prolonged oxidative stress. Fortunately, nature has a built-in mechanism for bringing things back into balance: Antioxidants.

    Antioxidants have the remarkable ability to neutralize free radicals before they cause harm. Some are produced by the body, while others can be consumed in the form of vitamins and other phytonutrients, like quercetin.

    And when it comes to antioxidant potential, quercetin is exceptional. In 2011, research published in the book series Advances in Experimental Medicine and Biology showed the flavonoid to have more than three times the Total Antioxidant Capacity (TAC) as curcumin.

    In other studies, quercetin showed the ability to increase antioxidant enzymes in red blood cells, prevent DNA damage, and promote DNA repair.

    In addition to the activities listed above, quercetin has been shown to promote the body’s natural production of other endogenous antioxidants to further aid in reducing oxidative stress, bolstering immunity, and regulating healthy cellular reproduction and longevity.

    Reduced Inflammation

    In a cell-based study, quercetin was shown to reduce inflammation by inhibiting the pathways and chemical messengers that are known to cause an inflammatory response. Four key findings from this study include:

    • Quercetin appears to block the activation of NF-κB, a critical signaling network that modulates the human inflammation response. NF-κB is a pro-inflammatory pathway that is activated in times of stress.
    • Quercetin seems to down-regulate this pathway, helping to alleviate stress response and reduce corresponding inflammation.
    • Quercetin also appears to block the MAKP pathway. MAKP can be thought of as an on/off switch that allows one cell to communicate with its neighbors.
    • By keeping this pathway switched “off”, quercetin appears to inhibit the spread of inflammatory signals from cell-to-cell.
    • Quercetin also appears to suppress certain inflammatory cytokines, specifically IL-1β and IL-6.
    • The immune system uses these chemical messengers to induce inflammation; by suppressing them, quercetin is thought to act as an anti-inflammatory.
    • Finally, quercetin appears to promote an anti-inflammatory cytokine called IL-10. Anti-inflammatory cytokines function opposite the cytokines described above, acting to reduce swelling and promote healing.

    Reduced Symptoms of Metabolic Syndrome

    Metabolic syndrome is characterized by high blood pressure, blood sugar, cholesterol, and body fat.

    Metabolic syndrome is typically progressive as symptoms worsen over time. Together, these conditions increase the risk of cardiovascular disease, stroke, and type 2 diabetes.

    A 2021 meta-analysis of metabolic syndrome research articles shows evidence that quercetin improves critical elements of healthy metabolism. According to the analysis, quercetin may reduce blood glucose levels, blood pressure, insulin resistance, and rates of obesity.

    In a separate cell-based study, quercetin was also shown to be an effective inhibitor of LDL (“bad”) cholesterol oxidation.

    This is a key finding, as LDL oxidation is known to wreak havoc on the cardiovascular system, increasing incidence of inflammation, atherosclerosis, blood clots, and risk of heart attack.

    Obesity Prevention

    According to the Journal of the American Medical Association, obesity kills about 280,000 Americans every year.

    In addition to curbing calories, plant-based diets provide a wide array of anti-obesity phytonutrients. Quercetin has shown promise as one such compound.

    In 2008, researchers discovered quercetin had the ability to mediate both AMPK and MAPK networks—two key signaling pathways that influence cellular activity and inflammation.

    In doing so, quercetin demonstrated the ability to slow adipogenesis, the process by which fat cells develop and accumulate in the body.

    In a 2015 study involving both cell and animal models, quercetin again showed the ability to suppress both creation and accumulation of fatty tissue by down-regulating the MAPK signaling pathway.

    As a result, mice that received quercetin experienced an astounding 40% decrease in body weight. Commenting on the study, researchers noted “quercetin may represent a potential therapeutic agent for other metabolic disorders” and suggest further investigation in humans.

    In another cell-based study, onion-derived quercetin was found to convert white fatty tissue into brown fatty tissue.

    Modern longevity research has been increasingly interested in the role of brown fatty tissue in preventing obesity and related diseases. Writing for MayoClinic.org, Donald Hensrud, MD, explains that brown fat is activated when humans feel cold.It has more mitochondria than normal fatty tissue, and it has the unique ability to burn the body’s excess fat stores when activated.

    In addition to keeping warm, this process also increases total fat utilization, which may prevent excess accumulation that leads to obesity.

    Researchers have also noted that brown fat may “increase thermogenesis and help achieve long-lasting weight loss and an improved metabolic profile”.

    Type 2 Diabetes Prevention

    As noted above, meta-analysis of metabolic syndrome research highlights the potential of quercetin to stabilize blood sugar and reduce the incidence of insulin resistance. In turn, these potential benefits may ward off the onset of type 2 diabetes. But how?

    A 2017 cell-based study sheds light on this mechanism, explaining that quercetin inhibits glucose utilization in the intestine and increases glucose utilization in peripheral tissues.

    Though the results are promising, the authors of the study warn that human trials are needed to further explore quercetin’s anti-diabetic potential in humans.

    And while human trials are needed, animal studies have already shown promise. A systematic review of quercetin literature published by the journal Biomedicine and Pharmacology provides substantial evidence from rodent studies indicating quercetin’s ability to improve symptoms of rodents with diabetes.

    Improved Brain Health and Memory

    Quercetin has also shown promise as a neuro-protectant in various cell-based and animal studies. In a 2018 review of such studies, the following pathways and receptors were identified as possible mechanisms of action:

    Most recently, an article published in the November 2021 edition of Scientific Report named quercetin as a possible therapeutic in the fight against Alzheimer’s Disease.

    Improved Mood

    Quercetin may also help to improve mood. In general, plant-derived flavonoids are thought to have an impact on mood and cognitive function through two main mechanisms: Altering brain kinase activation and neuronal communication, and acting as an adenosine A1 receptor agonist.

    For context, consider that caffeine is perhaps the most common adenosine agonist in the Western world. Just as a warm cup of coffee or tea produces a subtle lift in mood, so too does quercetin—at least in animal studies.

    One study expanded on this finding, demonstrating quercetin’s ability to alleviate symptoms of depression in rodents.

    Additionally, quercetin appears to provide an anti-anxiety effect in at least one separate rodent study. Commenting on the results, researchers attribute the effects to quercetin’s ability to reduce inflammation and modulate brain derived neurotrophic factor (BDNF), thus alleviating anxiety-like behaviors.

    Reduced Risk of Cancer

    Quercetin may also help to reduce the risk of cancer by halting its spread. In a study published by the journal Nature, quercetin was found to enhance certain drugs that inhibit the proliferation of cancer cells.

    Although this does not mean quercetin alone can stop the progression of cancer, it does indicate the compound’s potential to play a role in augmenting existing cancer treatments.

    In 2011, a cell-based study of quercetin demonstrated a more direct means of preventing the spread of cancer. Studying breast cancer cells, researchers found quercetin to “significantly suppress” COX-2 mRNA and protein expression, thereby preventing cellular growth and proliferation.

    Quercetin also shows promise as a potent antioxidant and natural anti-inflammatory, as illustrated in the How Does Quercetin Work section above.

    Through these mechanisms of action, the plant compound may indirectly reduce the risk of cancer by promoting cellular longevity, reducing oxidative stress, and regulating the immune system.

    Allergy Relief

    Quercetin also shows an ability to reduce allergic response. In a 2016 article published by the peer-reviewed journal Molecules, authors note quercetin demonstrated efficacy as a histamine inhibitor.

    Potential Health Risks and Side Effects

    Quercetin is a plant compound, and it is commonly ingested in small amounts as part of a healthy plant-based diet. As indicated above, the compound is also “Generally Regarded As Safe” by the US Food and Drug Administration.

    However, taking high doses of quercetin over long periods of time may have certain risks and side effects. More research is needed to determine what those side effects are.

    Individuals must always consult a physician prior to taking a new supplement, and that is especially important when combining new supplements with existing medications.

    In animal studies, quercetin has been shown to exacerbate kidney damage. This is particularly dangerous for individuals who currently take prescription medications that are known to be damaging to the kidneys.

    Quercetin exhibits several adverse reactions with common prescription drugs, including:

    Conclusion: Quercetin is a Potentially Powerful Longevity Tool

    Flavonoids like quercetin are vital tools in the fight against aging and age-related disease. Decades of cell, animal, and human studies support quercetin’s efficacy as a potent antioxidant, anti-inflammatory, and anti-viral compound.

    Remarkably, this unique phytochemical shows exceptional promise as a treatment for reducing symptoms and preventing infection.

    Although some studies indicate quercetin to be toxic in high doses for prolonged periods of time, the supplement is “Generally Regarded as Safe” by the US Food and Drug Administration. Outlook is generally positive, and it will be exciting to see what future clinical trials teach us about this powerful longevity compound.

    If you have any questions about this article, or would like to feature, please contact support@vitality-pro.com.

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