Antioxidant Benefits of Quercetin for Longevity

Renowned for its potent antioxidant and anti-inflammatory properties, quercetin is an antioxidant that helps protect the body from oxidative stress and chronic inflammation—two major contributors to aging and age-related diseases. Additionally, quercetin is classified as a senolytic agent, meaning it can target and eliminate damaged, aging cells that accumulate over time.

Quercetin also exhibits anti-glycation effects, preventing the formation of harmful compounds known as advanced glycation end products. These compounds can accelerate aging and cause cellular damage, adversely impacting the skin, blood vessels, and vital organs like the brain. By inhibiting glycation, quercetin helps preserve cellular integrity and supports overall health as we age.

While quercetin is present in various foods, including apples, onions, and berries, dietary sources often provide limited and variable amounts. Quercetin supplements offer higher, more concentrated doses, making them an effective way to maximize its health benefits. 

In this article, we will explore the diverse advantages of quercetin, its role in combating aging and promoting longevity, and how supplementation may offer benefits beyond what dietary intake alone can achieve.

What Is Quercetin?

Quercetin is a naturally occurring flavonoid, a type of polyphenolic compound abundant in a wide range of onions, fruits, vegetables, grains, and herbs.  It belongs to a large family of plant pigments, also named as Vitamin P, known for their antioxidant properties, which help protect plants from environmental stressors like ultraviolet radiation and pathogens (1). 

In humans, quercetin offers numerous health benefits, primarily due to its ability to modulate various biological pathways that promote cellular health and longevity.

At the molecular level, quercetin functions in several important ways:

• As a potent antioxidant that neutralizes harmful free radicals (2).

• As a regulator of key signaling pathways involved in maintaining cellular homeostasis and supporting tissue regeneration (3).

• As a modulator of the cell cycle, ensuring proper cellular function and preventing uncontrolled cell proliferation (4).

• As a facilitator in cellular repair mechanisms, aiding in the recovery of damaged cells (5).

One of the remarkable aspects of quercetin’s action is its high selectivity. Rather than inducing random apoptosis, quercetin specifically targets aging and cancer cells for programmed cell death. It's particularly effective in clearing senescent cells and maintaining other pathways involved in aging and longevity.

Antioxidant and Anti-inflammatory Properties

One of quercetin's most significant advantages is its powerful antioxidant activity. As a flavonoid, quercetin helps neutralize harmful free radicals, which are unstable molecules that contribute to oxidative stress, a key factor in cellular damage, aging, and a variety of chronic diseases.

Quercetin neutralizes these free radicals by donating electrons, effectively preventing their damaging effects. Research shows that quercetin may help ward off conditions such as osteoporosis, certain cancers, tumors, lung diseases, and cardiovascular disorders.

Quercetin's antioxidant properties work by (2):

1. Increasing the body's antioxidant capacity, particularly by regulating glutathione levels (6);

2. Boosting the expression of antioxidant enzymes like Cu/Zn SOD, Mn SOD, catalase, and GSH peroxidase (7);

3. Enhancing antioxidant defenses through pathways like Akt and p38/MAPK. (3);

4. Protecting against UVB-induced damage by eliminating ROS and fortifying cell membranes and mitochondria (8);

5. Modulating antioxidant-related gene expression to further combat oxidative stress (9).

Overall, quercetin plays a crucial role in balancing oxidant and antioxidant activity, effectively reducing oxidative stress.

Beyond its antioxidant effects, quercetin also exhibits powerful anti-inflammatory properties. 

Chronic inflammation is a significant factor in aging and numerous age-related diseases. At the molecular level, quercetin inhibits NF-κB, a family of transcription factors that regulate genes associated with inflammation, carcinogenesis, and cell protection. By suppressing NF-κB and activator protein 1, quercetin decreases the production of inflammatory molecules like cytokines and chemokines, which drive and maintain chronic inflammation (10).

Additionally, quercetin reduces the activity of COX-2 (an enzyme that generates pro-inflammatory prostaglandins) and 5-LOX (which produces leukotrienes, another set of inflammatory mediators). Through these mechanisms, quercetin effectively curbs inflammation and supports overall health (11).

Quercetin as a Senolytic

Senolytics are a class of compounds designed to selectively target and eliminate senescent cells, which accumulate in tissues as we age (as previously discussed here). 

Senescent cells are aged, non-dividing cells that, while no longer replicating, remain metabolically active and release harmful factors collectively known as the senescence-associated secretory phenotype (SASP). SASP includes inflammatory cytokines, proteases, and growth factors that create a toxic environment, impairing healthy cellular function and accelerating age-related decline.

Quercetin has attracted significant attention as a senolytic agent, meaning it can selectively clear senescent cells and mitigate their negative impact on health. Studies have shown that quercetin effectively removes these aged cells, leading to improved tissue regeneration, enhanced function, and better maintenance of cellular homeostasis (12).

A hallmark trait of senescent and cancer cells is their resistance to initiating apoptosis  (programmed cell death), even when accumulating significant errors (damaged organelles, misfolded proteins etc). The ability to re-engage these cell death mechanisms is crucial for promoting longevity. 

Quercetin addresses this challenge by interacting with BCL-2 family proteins, which are key regulators of apoptosis (13). Specifically, quercetin binds to the BH3 domain of Bcl-2 and Bcl-xL proteins, inhibiting their activity and promoting apoptosis in both cancerous and senescent cells. This precise binding underpins quercetin’s high specificity in targeting dysfunctional cells.

Moreover, quercetin alleviates the harmful effects of SASP by modulating inflammatory pathways and reducing the expression of markers like p21 (14). This action further diminishes chronic inflammation, supporting overall tissue health and mitigating age-related damage.

Quercetin as an Anti-glycation Agent

Glycation is a natural biochemical process where sugar molecules, such as glucose and fructose, bind to proteins, lipids, or nucleic acids, forming harmful compounds known as Advanced Glycation End-products (AGEs). While this process occurs naturally over time, excessive glycation accelerates aging and contributes to the development of a variety of age-related diseases. 

Over time, these AGEs accumulate and become one of the main contributors to skin aging, particularly in the formation of wrinkles. 

When AGEs form, they cause key structural proteins, such as elastin and collagen, to cross-link. These proteins are essential for maintaining skin elasticity and firmness, but when they become cross-linked, they stiffen, leading to a loss of elasticity. This results in sagging, as well as the development of fine lines and wrinkles. 

As AGEs build up with age, they accelerate the decline in the skin's ability to regenerate, leading to visible signs of aging and a decrease in overall skin elasticity.

Quercetin is also recognized for its anti-glycation effects. 

Research has shown that quercetin works through several key mechanisms to reduce the formation of AGEs:

1. Inhibition of AGE Formation: Quercetin has been demonstrated to block the initial steps of the glycation process by interfering with the reaction between sugars and proteins. By doing so, it prevents the formation of reactive carbonyl compounds, which are precursors to AGEs (15).

2. Protecting Tissues from AGE-Induced Damage: By preventing glycation and the formation of AGEs, quercetin helps protect cellular components from AGE-induced cross-linking and dysfunction. This is particularly beneficial for collagen and elastin in connective tissues, which are key for maintaining the flexibility and integrity of skin, joints, and blood vessels. Additionally, quercetin has been shown to mitigate the inflammatory response that AGEs provoke in tissues, further reducing the damage they cause (16).

3. Reducing AGE-Induced Oxidative Stress: AGEs not only damage proteins directly but also contribute to the production of reactive oxygen species (ROS), which cause oxidative stress. Quercetin’s antioxidant properties help reduce oxidative damage induced by AGEs, offering additional protection to cells and tissues.

By targeting glycation pathways, quercetin contributes to protecting cellular structures, preserving tissue elasticity, and reducing the onset of age-related diseases. 

Food Sources vs. Supplements

Dietary Sources of Quercetin

Quercetin is a naturally occurring flavonoid found in a variety of plant-based foods, particularly fruits, vegetables, and herbs. Common sources of quercetin include:

• Onions: Onions, especially the red variety, are among the richest dietary sources of quercetin. 

• Apples: Apples, particularly their skin, are also high in quercetin, besides red apples containing more quercetin than green ones.

• Berries: Blueberries, blackberries, and cranberries are excellent sources of quercetin.

• Citrus fruits: Oranges, lemons, and grapefruits contain quercetin, though in lower concentrations compared to berries and apples.

• Grapes: Particularly red and purple grapes, quercetin is found in the skins, where it helps protect the fruit.

• Leafy greens: Kale, spinach, and other dark leafy greens.

• Other sources: Lesser amounts of quercetin can be found in foods like cherries, broccoli, and peppers.

While these foods are rich in quercetin, there are limitations when it comes to obtaining effective doses through diet alone.

Limitations of Dietary Quercetin

1. Variability in Content: The quercetin levels in foods can vary significantly depending on factors such as the growing conditions, storage duration, and preparation methods (e.g., raw versus cooked).

2. Bioavailability: Quercetin from food has relatively poor absorption. It is often bound to sugar molecules, which makes it less bioavailable and more difficult for the body to process effectively.

3. Effective Dose from Food: Achieving a therapeutic dose of quercetin through diet is challenging. For instance, a typical onion (one of the richest quercetin sources) contains about 28.4–48.6 mg of quercetin per 100 grams. To reach an effective dose of 500 mg, you would need to consume around 2 kilograms (or 4.4 lbs. of onions). Such an amount is impractical to incorporate into a regular diet, underscoring the difficulty of meeting effective quercetin levels solely through food intake.

Why Quercetin Supplements are More Effective:

While dietary sources of quercetin certainly offer health benefits, supplementing with quercetin provides a more consistent and reliable dose of the flavonoid. This is where supplementation, such as Jung’s Longevity Foundation, comes in.

Advantages of Quercetin Supplements

• Consistent Dosage: Quercetin supplements provide a standardized and precise dose, ensuring that you consistently receive the necessary amount for optimal health benefits.

• Improved Bioavailability: Many quercetin supplements are specially formulated to enhance absorption, overcoming the natural bioavailability challenges associated with dietary sources.

• Convenience: Taking a supplement is a simple and efficient way to get a potent and reliable dose of quercetin without needing to consume large quantities of quercetin-rich foods to meet recommended levels.

• Comfortable Form: Supplements are available in easy-to-consume formats, such as capsules, tablets, or powders, making them more accessible and less cumbersome than dietary sources.

• Formulations with Other Ingredients: Many supplements combine quercetin with other beneficial compounds, such as astaxanthin, fisetin, or  pterostilbene, to enhance effectiveness and provide additional health benefits.

Incorporating Quercetin into Your Longevity Plan

Integrating quercetin into your daily health routine is an effective way to promote healthy aging and overall well-being. To maximize the benefits of quercetin, it’s essential to pay attention to both the timing and dosage of supplementation.

• Dosage: Most people take a daily dose ranging from 200 to 1,000 mg to support cellular health, reduce inflammation, and boost antioxidant defenses.

• Timing: Taking quercetin with meals can enhance absorption, especially when paired with healthy fats that improve the flavonoid’s bioavailability. Depending on your health goals, quercetin supplements can be taken in the morning or distributed throughout the day. Many individuals find that incorporating quercetin into their morning routine helps kickstart antioxidant protection and supports metabolic functions.

As with any supplement, consistency is crucial for achieving optimal, long-term benefits.

Synergistic Effects of Quercetin with Other Longevity Ingredients

One of the standout features of Jung’s Longevity Foundation is its synergistic formulation designed to support a variety of longevity mechanisms. The inclusion of quercetin within this comprehensive blend works in tandem with other key ingredients, amplifying their individual benefits and optimizing the body’s ability to age healthily.

• AMPK Activation: Quercetin together with pterostilbene works to activate AMPK, a master regulator of energy balance, which plays a critical role in promoting cellular repair, fat metabolism, and the inhibition of aging-related pathways like mTOR (17,18).

• Mitochondrial Health: Both quercetin and other ingredients in the formulation, such as oleuropein, support mitochondrial function by reducing oxidative stress and improving energy production (19). 

• SIRT1 Activation: Quercetin and pterostilbene have been shown to activate SIRT1, a protein involved in regulating cellular health, DNA repair, and inflammation reduction. When combined with other sirtuin-activating compounds, such as niacin, quercetin helps to further enhance these protective pathways, supporting long-term health and resilience against age-related diseases (20). Olive leaf extract, fisetin, and spermidine also help to amplify quercetin's effects.

• Anti-inflammatory and Antioxidant Synergy: Quercetin’s powerful anti-inflammatory and antioxidant properties work harmoniously with other agents, like astaxanthin and fisetin, to reduce oxidative stress and protect cells from its negative effect.

• Gut Health: Quercetin and spermidine can help maintain the integrity of the gut barrier, which is typically compromised in dysbiosis (21, 22).

By taking a holistic approach (supplements, diet, physical activity) to longevity, you can optimize your body's ability to defend itself against age-related changes, supporting not only a longer, but also a more vibrant life.

Potential Side Effects and Considerations

While quercetin is generally considered safe and well-tolerated for most people, it is important to be mindful of potential side effects and interactions, particularly when incorporating it into your routine as a supplement. 

In general, quercetin has a good safety profile when taken in moderate doses. However, like any supplement, it can cause some mild side effects in certain individuals. These may include:

• Headaches: Some individuals may experience mild headaches, especially if they are sensitive to flavonoids.

• Digestive Upset: A small percentage of people may experience gastrointestinal issues such as nausea, bloating, or diarrhea when taking quercetin.

• Allergic Reactions: Although rare, some individuals may experience an allergic reaction to quercetin, especially those with sensitivities to certain plants or pollen.

To minimize the risk of side effects, it's advisable to start with a lower dose and gradually increase it as tolerated. Taking quercetin with food can also help reduce the likelihood of digestive upset.

Quercetin and Medication Interactions

Quercetin can potentially interact with certain medications, so it’s important to be cautious if you are on prescribed treatments. Some known interactions include:

• Blood Thinners: Quercetin may have a mild anticoagulant effect, meaning it could potentially increase the risk of bleeding if taken alongside blood-thinning medications like warfarin or aspirin.

• Antihypertensive Medications: As quercetin may lower blood pressure, there could be a risk of excessively lowering blood pressure when combined with antihypertensive drugs.

• Cytochrome P450 Enzyme System: Quercetin can affect the CYP450 enzyme system, which is responsible for metabolizing many medications. This could alter the effectiveness of certain drugs, particularly those processed by this system (23).

Consulting a Healthcare Provider

Before introducing quercetin or any new supplement into your health regimen, especially if you are pregnant, nursing, or have underlying health conditions, it is always best to consult with a healthcare provider.

Key Takeaways on Quercetin's Benefits for Longevity

This exploration of quercetin highlights its potential to support healthy aging, cellular repair, and overall longevity.

Renowned for its potent antioxidant and anti-inflammatory effects, quercetin plays a pivotal role in combating oxidative stress and chronic inflammation—two primary drivers of aging and age-related diseases. As a natural senolytic, quercetin aids in the removal of damaged, aging cells, promoting tissue regeneration and cellular homeostasis. Additionally, its anti-glycation properties help prevent the formation of harmful advanced glycation end-products (AGEs), protecting collagen, elastin, and vital organs from damage associated with aging.

References:

1. The role of quercetin in plants (2021). Plant Physiology and Biochemistry.

2. Health effects of quercetin: from antioxidant to nutraceutical (2008). European Journal of Pharmacology.

3. Antioxidant Activities of Quercetin and Its Complexes for Medicinal Application (2019). Molecules. 

4. Potential Therapeutic Targets of Quercetin, a Plant Flavonol, and Its Role in the Therapy of Various Types of Cancer through the Modulation of Various Cell Signaling Pathways (2021). Molecules.

5. Role of Quercetin in DNA Repair: Possible Target to Combat Drug Resistance in Diabetes (2024). Current Drug Targets.

6. Quercetin modulates Nrf2 and glutathione-related defenses in HepG2 cells: Involvement of p38 (2012). Chemico-Biological Interactions.

7. Pretreated quercetin protects gerbil hippocampal CA1 pyramidal neurons from transient cerebral ischemic injury by increasing the expression of antioxidant enzymes (2017). Neural Regeneration Research.

8. Protective effects of quercetin on UVB irradiation-induced cytotoxicity through ROS clearance in keratinocyte cells (2017). Oncology Reports.

9. Quercetin reduces oxidative damage induced by paraquat via modulating expression of antioxidant genes in A549 cells (2013). Journal of Applied Toxicology.

10. Polyphenol Compound as a Transcription Factor Inhibitor (2015). Nutrients. 

11. Quercetin Suppresses Cyclooxygenase-2 Expression and Angiogenesis through Inactivation of P300 Signaling (2011). PLoS ONE. 

12. Senolytic effects of quercetin in an in vitro model of pre-adipocytes and adipocytes induced senescence (2021). Scientific Reports.

13. Direct binding of Bcl-2 family proteins by quercetin triggers its pro-apoptotic activity (2014). ACS Chemical Biology Journal.

14. Quercetin Enhances Ligand-induced Apoptosis in Senescent Idiopathic Pulmonary Fibrosis Fibroblasts and Reduces Lung Fibrosis In Vivo (2019). American Journal of Respiratory Cell and Molecular Biology.

15. Inhibitory effect of quercetin in the formation of advance glycation end products of human serum albumin: An in vitro and molecular interaction study (2015). International Journal of Biological Macromolecules.

16. Quercetin ameliorates advanced glycation end product-induced wound healing impairment and inflammaging in human gingival fibroblasts (2023). Journal of Dental Sciences.

17. Autophagy-inducing effect of pterostilbene: A prospective therapeutic/preventive option for skin diseases (2017). Journal of food and drug analysis. 

18. Quercetin induces pro-apoptotic autophagy via SIRT1/AMPK signaling pathway in human lung cancer cell lines A549 and H1299 in vitro (2021). Thoracic cancer. 

19. Mitochondrial Calcium Uptake Declines during Aging and is Directly Activated by Oleuropein to Boost Energy Metabolism and Skeletal Muscle Performance (2023). bioRxiv. 

20. Hung C.H., Chan S.H., Chu P.M., Tsai K.L. Quercetin is a potent anti-atherosclerotic compound by activation of SIRT1 signaling under oxLDL stimulation (2015). Molecular Nutrition & Food Research. 

21. Reshaping faecal gut microbiota composition by the intake of trans-resveratrol and quercetin in high-fat sucrose diet-fed rats (2015). The Journal of Nutritional Biochemistry. 

22. Spermidine Ameliorates Colitis via Induction of Anti-Inflammatory Macrophages and Prevention of Intestinal Dysbiosis (2023). Journal of Crohn's and Colitis.

23. Inhibitory Effects of Quercetin and Its Main Methyl, Sulfate, and Glucuronic Acid Conjugates on Cytochrome P450 Enzymes, and on OATP, BCRP and MRP2 Transporters (2020). Nutrients.