Quercetin is a bioactive compound that exerts antioxidant and anti-inflammatory properties.[1] Research indicates that quercetin may alleviate chronic health conditions such as hypertension, neurodegenerative disease, arthritis, and lung and kidney diseases and may be beneficial in combating aging-related diseases. Although much of the quercetin research has been performed in animals, some clinical trials have been conducted and others are ongoing.

A naturally occurring member of the flavonoid class of plant polyphenol compounds, quercetin is found in a wide variety of fruits and vegetables, especially red and yellow onions, capers, apples, blueberries, and peppers.[2] Quercetin is the most abundant flavonoid in the human diet, but the quantity of quercetin in fruits and vegetables varies according to growing practices.[3] [4] Also known as 3,3',4',5,7-pentahydroxyflavone, quercetin is widely available as a dietary supplement. (Figure 1.)

Figure 1. Quercetin content of commonly consumed foods.[5]

Quercetin and health

Robust scientific evidence indicates that quercetin demonstrates a wide range of health-promoting characteristics, including antioxidant, anti-inflammatory, and anti-aging properties. It scavenges reactive oxygen and nitrogen species, inhibits activation of the proinflammatory molecule nuclear factor kappa B (NF-κB), and downregulates the inflammatory response of macrophages. (Figure 2.)

Quercetin as dual mechanism antioxidant

Quercetin's antioxidant properties stem from its capacity to act as a direct antioxidant by scavenging reactive oxygen and nitrogen species – highly reactive ions generated during metabolic processes or from exogenous sources such as pollution, radiation, or others. These molecules can accumulate in the body and promote oxidative damage to DNA, proteins, and lipids. Quercetin can perform its antioxidant role by forming complexes with metal ions, thus preventing further free radical initiation. Furthermore, quercetin can act as an indirect antioxidant by activating antioxidant enzymes and inhibiting oxidative enzymes, a property shared by other similar bioactive compounds like sulforaphane. Oxidative damage plays a role in the aging process, contributing to chronic and degenerative conditions. Some research indicates that consuming polyphenols such as quercetin can decrease the risk of aging-related diseases, including cardiovascular disease.

Quercetin and inflammation

Inflammation is a critical element of the body’s immune response. Acute inflammation occurs when the body is exposed to harmful stimuli, such as pathogens, damaged cells, or irritants. Chronic inflammation, however, which occurs with obesity or certain disease states, damages cellular components, and contributes to ill health. Quercetin exerts its inflammatory activity by inhibiting inflammatory enzymes, including cyclooxygenase and lipoxygenase, as well as by decreasing prostaglandins and leukotrienes — well-known inflammatory mediators.

In a mouse model of inflammation, quercetin provided in the diet for 14 days decreased proinflammatory markers including serum amyloid A, fibrinogen, and C-reactive protein (CRP).[6] The findings that quercetin acts as an anti-inflammatory agent have not been reproduced consistently in human studies, possibly due to differing methodologies, some of which studied quercetin in conjunction with other compounds.

A series of meta-analyses involving 925 participants across 15 randomized placebo-controlled clinical trials explored the anti-inflammatory effect of quercetin supplementation in both healthy adults and people who had been diagnosed with a disease, including type 2 diabetes, metabolic syndrome, coronary artery disease, rheumatoid arthritis, and obesity. The duration of the various trials ranged from two to ten weeks. Researchers investigated quercetin's capacity to decrease CRP, interleukin (IL)-6, and tumor necrosis factor-alpha (TNF-alpha). Analysis of six studies involving 348 participants revealed that quercetin reduced CRP in those over the age of 40 years, as well as those who had been diagnosed with a disease. Five studies involving 274 participants suggested that IL-6 decreased in female participants and those diagnosed with a disease, particularly at doses of 500 milligrams per day or greater. Four studies involving 303 people showed that quercetin reduced TNF-alpha, but only after one of the studies was removed from the analysis. In summary, quercetin did not exert an effect on systemic inflammation in healthy people given low doses. However, quercetin lowered inflammation — as measured by reduced CRP and IL-6 — in participants diagnosed with a disease.[7]

" Analysis of six studies involving 348 participants revealed that quercetin reduced CRP in those over the age of 40 years, as well as those who had been diagnosed with a disease. " Click To Tweet

Findings from a meta-analysis of seven randomized controlled studies involving both healthy adults and people with type 2 diabetes, rheumatoid arthritis, and obesity revealed that quercetin reduced CRP, particularly at doses higher than 500 milligrams per day.[8] Another meta-analysis of 16 randomized controlled trials revealed that people with metabolic syndrome who supplemented with quercetin experienced lower total and LDL cholesterol and CRP levels, while HDL cholesterol, triglycerides, and inflammatory markers such as IL-6 and TNF-alpha remained the same.[9]

" Another meta-analysis of 16 randomized controlled trials revealed that people with metabolic syndrome who supplemented with quercetin experienced lower total and LDL cholesterol and CRP levels " Click To Tweet

Figure 2. Quercetin exerts a wide range of health-promoting properties, including antioxidant, anti-inflammatory, antibacterial, and antiviral activities. When used in conjunction with the anticancer drug dasatinib, quercetin is a potent senolytic compound that exerts anti-aging properties by clearing senescent cells from tissues. (Adapted)[10]

Quercetin and chronic diseases

Quercetin's antioxidant and anti-inflammatory properties may be beneficial in preventing many chronic diseases, including cardiovascular disease, obesity, rheumatoid arthritis, and others.

Quercetin and cardiovascular disease

Quercetin and hypertension

Hypertension, or high blood pressure, damages blood vessels. If untreated, the condition can lead to heart disease and stroke, two of the leading causes of death worldwide. Preclinical evidence suggests that quercetin acts in a variety of ways that promote cardiovascular health. Several studies in hypertensive animal models demonstrate that quercetin decreases blood pressure and improves endothelial function.[11]

Human studies demonstrate similar effects on cardiovascular health, particularly in lowering blood pressure. A clinical study assessed the effects of 100 milligrams of quercetin versus a placebo taken daily for 10 weeks in a randomized double-blind, placebo-controlled trial involving 92 healthy male smokers.[12] The men who took quercetin modestly experienced decreased systolic and diastolic blood pressures compared to those who took the placebo. Furthermore, they saw improvements in total, LDL, and HDL cholesterol and blood glucose levels. Abnormal cholesterol and blood glucose levels are risk factors for cardiovascular disease. These findings suggest that quercetin may be beneficial in the prevention of cardiovascular disease. In another double-blind randomized clinical trial involving 72 women with type 2 diabetes, supplementation of 500 milligrams of quercetin daily for 10 weeks reduced systolic blood pressure by an average of eight points, but inflammatory markers remained unchanged.[13]

" … supplementation of 500 milligrams of quercetin daily for 10 weeks reduced systolic blood pressure by an average of eight points… " Click To Tweet

A meta-analysis of seven clinical trials examined the effect of quercetin on blood pressure in 587 men and women who had type 2 diabetes or smoked, women with rheumatoid arthritis, and healthy adults.[14] Quercetin doses ranged from 100 to 1,000 milligrams per day and the trial durations ranged from four to 10 weeks. In general, the trials demonstrated that quercetin was effective in lowering blood pressure, particularly at doses above 500 milligrams per day.

Findings from a recent meta-analysis of 17 randomized placebo-controlled clinical trials involving 896 adults (including healthy people and those with type 2 diabetes, hypertension, or obesity) suggested that people who took quercetin for at least two weeks had reduced systolic and diastolic blood pressure.[15] The authors observed that the blood pressure-lowering effects varied depending on the dosage, duration of treatment, and the formulation used. They suggested that quercetin is a suitable agent to be used as an adjunct therapy to control hypertension.

"Preclinical evidence suggests that quercetin shows promise in treating atherosclerosis, the build-up of plaque in the arteries, which can lead to heart attack and stroke." Click To Tweet

Quercetin and atherosclerosis

Preclinical evidence suggests that quercetin shows promise in treating atherosclerosis, the build-up of plaque in the arteries, which can lead to heart attack and stroke. In a two-part study to compare quercetin's effect on the progression and regression of atherosclerosis, researchers fed two groups of rabbits a diet designed to induce high cholesterol for 90 days. One group received 25 milligrams per kilogram of body weight (mg/kg/bw) of supplemental quercetin while the other group served as the control. During the second part of the experiment, the authors fed an additional twelve animals a high cholesterol diet for 90 days, followed by 90 days of a normal diet either alone or supplemented with quercetin. Quercetin decreased atherosclerotic lesions in the rabbits' aortas and reduced inflammatory enzymes and CRP in both dietary conditions. These findings suggest that quercetin ameliorates the inflammatory effects of an unhealthy diet in rabbits while atherosclerosis in the early stages. In addition, findings from a meta-analysis of eleven rodent studies suggest that flavonols can reduce aortic atherosclerotic lesions in some animal models.[16]

The preclinical studies suggesting that quercetin can suppress oxidative stress, reduce the inflammatory response, and decrease atherosclerotic lesions have been difficult to replicate in humans — possibly due to small, non-standardized trials using different amounts and sources of quercetin.[17] Larger and more rigorous clinical trials are needed to determine whether quercetin reduces atherosclerosis in humans.

Quercetin and obesity

Preclinical research suggests that quercetin can reduce body weight and decrease visceral fat and fat accumulation in the liver, called hepatic steatosis. In mice fed an obesogenic diet, quercetin increased energy expenditure and decreased inflammatory markers.[18] In another study, quercetin intake reduced hepatic steatosis of mice fed a Western-style diet.[19]

Adipose tissue macrophages are cells involved in obesity-associated inflammation and insulin resistance. In mice fed an obesogenic diet, quercetin suppressed adipose tissue macrophage infiltration and inflammation through the AMPK/SIRT1 pathway — a biological process that participates in sensing nutrients and regulating inflammation.[20] A study in rats indicated that quercetin improved many of the symptoms of metabolic syndrome.[21] Further research is needed to determine whether these findings translate to humans.

Quercetin and wound healing

Wounds need to heal quickly to prevent infection. However, if they heal too quickly, excessive fibrous tissue can form. This process, known as fibrosis, leads to scarring, which can cause both functional and cosmetic problems. Quercetin has antifibrotic properties, and some animal studies have shown the potential of quercetin to improve wound healing and reduce the formation of scars.

In one study, topical application of quercetin accelerated wound closure in a time-dependent manner.[22] The authors suggested that quercetin exerted its effects by altering growth factors and cytokine production. Another study in mice indicated that quercetin-treated mice healed at the same rate as those not treated, but less fibrosis was observed in the quercetin-treated animals — suggesting that quercetin may impact pro-fibrotic pathways.[23]

" In a rodent model of pressure ulcers, a wound treated with a quercetin solution every 48 hours for two weeks healed faster than an untreated wound on the same animal. " Click To Tweet

Pressure ulcers, also known as bedsores, can develop when a person is immobile for long periods of time. In a rodent model of pressure ulcers, a wound treated with a quercetin solution every 48 hours for two weeks healed faster than an untreated wound on the same animal. By the third day of the treatment, the quercetin-treated wound was 80 percent the size of the untreated wound. By the end of the two-week period, the treated wound was mostly closed while the untreated wound was only 80 percent healed. Moreover, fewer proinflammatory cytokines and immune cells were observed at the quercetin-treated wound site. Many studies have investigated (or are currently investigating) quercetin's mechanisms of action and its potential use for the treatment of wounds. One mechanism may involve the elimination of senescent cells (described in detail below) at the wound site, speeding up the healing process.[24]

Onion extract, which contains quercetin as well as other phenolic compounds, is an ingredient in many commercial scar gels. A meta-analysis of 13 studies involving 600 people who used scar gels found that methodologies differed markedly, with follow-up periods ranging from 10 weeks to six months.[25] Users experienced mixed results with the products, possibly due to differences in the formulations or the amount of quercetin they contained. Additional clinical research with standardized methods is needed to confirm whether quercetin has beneficial effects on wound healing in humans.

Other researchers report low clinical efficacy of quercetin as a scar improvement agent.[26] While many anecdotal reports of success with quercetin-containing commercial scar treatment products exist, additional clinical research is needed to confirm whether quercetin has beneficial effects on wound healing in humans.

Quercetin and viral infections

Preclinical data indicate that quercetin exhibits antiviral properties. One mechanism by which quercetin exerts its beneficial effects might lie in its capacity to serve as an ionophore. An ionophore is a compound that can transport ions across the semipermeable lipid bilayer that surrounds cells. Of particular relevance in viral disease is the movement of zinc, an essential nutrient that inhibits the action of RNA-dependent RNA polymerase — the enzyme critical for the reproduction of RNA viruses such as SARS-CoV-2, the virus responsible for COVID-19.[27] Essentially, zinc blocks the replication of viruses. However, zinc is a positively charged ion and cannot enter cells to perform this function without a transporter. Quercetin is a known ionophore. Clinical trials have demonstrated quercetin's inhibitory effect on the expression of the human ACE2 receptors and enzymes of SARS-CoV-2 (MPro, PLPro, and RdRp). Quercetin's antioxidant, anti-inflammatory, and immunomodulatory activity contribute to its therapeutic power.[28]

A randomized controlled trial involving more than 1,000 people indicated that supplementation with 1,000 milligrams of quercetin per day for 12 weeks was associated with a reduction in the rate and severity of upper respiratory tract infections in those over the age of 40 years, who rated themselves as physically fit.[29] Additional research is needed to confirm quercetin's antiviral capabilities.

Quercetin and rheumatoid arthritis

Rheumatoid arthritis is an autoimmune disease associated with chronic inflammation. It is characterized by swollen and painful joints and affects roughly 1 percent of people worldwide. A clinical study assessed the effects of 500 milligrams per day of quercetin versus a placebo for eight weeks in a randomized double-blind, placebo-controlled trial involving 50 women with rheumatoid arthritis.[30] The women who took the quercetin saw improvements in their clinical symptoms and had decreased plasma levels of high-sensitivity TNF-alpha, compared to the placebo group.

Quercetin and exercise

Exercise builds physical strength and endurance but can result in soreness that hampers recovery and impedes progress. Eccentric exercises are movements that occur when muscles are lengthened while still exerting force, such as when lowering a weight. While this type of exercise is a valuable part of athletic training, it is associated with muscle damage, weakness, soreness, and inflammation, resulting in strength loss. In one study, 12 healthy men (average age, 26 years) who consumed 1,000 milligrams of quercetin per day for 14 days exhibited less severe muscle weakness after a bout of eccentric exercise than those given a placebo.[31]

A meta-analysis of 11 prospective double-blinded clinical trials analyzed the effect of quercetin on exercise capability.[32] The doses ranged from 1 to 2 grams per day and the participants included men and women of various fitness levels. The authors of the study found that when combining the data of the 11 trials, exercise endurance capability increased only 3 percent, measured by VO2 max and endurance exercise performance. They concluded that the effect was trivial or, at most, small. Studies in mice have demonstrated more robust findings, however.[33]

Some animal studies have also shown that quercetin may blunt exercise-induced adaptations. In particular, oral quercetin supplementation in conjunction with treadmill exercise blunted exercise induced muscle and brain adaptations such as mitochondrial biogenesis in rats.[34] [35] [36] This may be a result of quercetin blocking the beneficial training adaptations that reactive oxygen species might mediate. R**eactive oxygen species** are highly reactive molecules produced during normal metabolic processes as well as during exercise as a consequence of exercise-induced immune activation.[37] Excessive exercise-induced reactive oxygen species can promote muscle damage, fatigue, and immune dysfunction, but the extent varies according to the duration and extent of exercise.[38] However, reactive oxygen species might also mediate beneficial training adaptations as a part of a biologically useful signaling cascade.[39] 

Studies in humans are needed to determine whether quercetin blunts any beneficial adaptations of exercise.

Quercetin and aging

Relevance of senolytic compounds in aging

Senescence is a condition or process of cellular deterioration that occurs with age. Senescent cells accumulate in the body over time and have properties that distinguish them from normal cells. For example, they stop replicating and, rather than dying, secrete harmful molecules that damage or kill neighboring cells.[40] [41] Dr. Rhonda Patrick's interview with senescence expert Dr. Judith Campisi

Research indicates that certain substances known as senolytic compounds may help treat many age-related diseases by clearing senescent cells from the body.[41] [42] For example, targeting senescent cells might benefit chronic conditions that reduce healthspan and lifespan, such as obesity and diabetes, because senescent cells accumulate in fat and other tissues in people with obesity and diabetes.[43] A study involving 40 obese and non-obese participants (average age, 59 years) found that markers of senescent cells were higher in the adipose tissue of obese people compared to non-obese people.[44] These findings suggest that an increase in senescent cell burden contributes to the inflammation and organ damage observed with obesity. The authors proposed that obesity triggers an early senescence program in the fat cells of obese people. Clearing these cells might alleviate the complications of these conditions and enhance insulin sensitivity.[45] In addition, decreasing senescent cells may reduce age-associated frailty.[46]

Clearing senescent cells with senolytic compounds is an emerging area of research that shows promise in treating or delaying chronic diseases of aging.

"Quercetin, one of the first senolytic compounds discovered, may have a beneficial effect against aging." Click To Tweet

Quercetin and dasatinib combination therapy

Quercetin, one of the first senolytic compounds discovered, may have a beneficial effect against aging. Quercetin is unable to kill all senescent cell types alone, but usually acts with another agent and is typically administered with dasatinib, an anti-cancer drug, in a combination commonly referred to as DQ in the scientific literature.

Preclinical evidence indicates that dasatinib + quercetin selectively clears senescent cells, leading to improvements in a variety of age-related diseases. A study of cells in culture found that dasatinib + quercetin decreased the number of senescent cells without affecting healthy cells. Similarly, the authors of a study in mice created a genetic model to demonstrate the health-promoting effects of clearing senescent cells.[47] They engineered the mice to carry a gene that, when activated with a drug, would selectively kill senescent cells. They administered the drug to mice twice a week, beginning when the mice were one year old and observed that the treated animals had an increase in median lifespan ranging from 17 to 35 percent. Furthermore, the treated mice had a more youthful appearance, delayed tumor formation, and less degeneration of organ tissues. These findings suggest that removal of senescent cells may be a strategy to extend healthy lifespan.

The "hit and run" treatment of senolytics

Based on the evidence from preclinical and preliminary clinical trials, senolytic agents such as quercetin can selectively clear senescent cells and affect the body in clinically important ways. These compounds typically have short half-lives in the body (less than six to 11 hours for the dasatinib + quercetin combination); however, numbers of senescent cells remain lower for many days following their administration. Researchers suggest this is because senescent cells do not divide. Rather, they take approximately one month to accumulate and start secreting inflammatory agents after being exposed to a stressor.[48] Investigators are hopeful that administering senolytics intermittently in what they term a "hit and run" approach, rather than continuously, will be effective and produce fewer side effects from dasatinib treatment.[49]

Quercetin improves median lifespan in animals

Data from a mouse study suggest that dasatinib + quercetin increased the median lifespan of mice by 36 percent, without extending the period of disease and physical dysfunction at the end of life.[46] Mice of varying ages were injected with senescent cells and some were intermittently administered the oral dasatinib + quercetin cocktail containing dasatinib (5 mg/kg/bw) and quercetin (50 mg/kg/bw), while other mice were not. The authors observed that young mice injected with senescent cells prematurely developed physical dysfunction, and the injection of fewer senescent cells was required to reduce the survival of older animals.

Mice that received the senolytic agent had decreased physical dysfunction and increased survival, suggesting that senescent cells can decrease healthspan and lifespan. The results of this study indicate that senescent cells are detrimental even to young animals, and senolytic agents such as quercetin can improve health and enhance lifespan in older mice. This study provided proof of principle that clearing senescent cells might have lifespan-enhancing effects in humans.

Cardiovascular disease is a major cause of death and disability, and its incidence increases with age. To determine if long-term treatment with a senolytic agent improves age-related vascular function, researchers gave two-year-old mice oral dasatinib (5 mg/kg/bw) and quercetin (10 mg/kg/bw) once monthly over a three-month period.[50] Another group of mice that had developed atherosclerotic plaques was treated with the same drug cocktail for two months. The authors of the study observed vascular improvements in both groups of animals. While atherosclerotic plaque size remained the same, plaque calcification — an indication of arterial stiffness that may precede cardiac events — decreased. This research indicates for the first time that the continual clearance of senescent cells improves vascular function and might be a treatment for cardiovascular disease. However, clinical trials are needed to determine whether these findings will translate to humans.

Quercetin and neurological diseases

Alzheimer's disease is a neurodegenerative disorder characterized by progressive memory loss, spatial disorientation, cognitive dysfunction, and behavioral changes. The pathological hallmarks of Alzheimer's disease include amyloid-beta plaques, tau tangles, and reduced brain glucose uptake. Senescent cells have been found in the brains of people with Alzheimer's disease upon autopsy.

In a mouse model of Alzheimer's disease, the build-up of senescent cells in the brain was associated with neurodegeneration. Mice given an intermittent treatment of dasatinib + quercetin (5 mg/kg/bw dasatinib with 50 mg/kg/bw quercetin) in biweekly intervals for three months starting at the age of 20 months exhibited decreased neuroinflammation and partly reversed brain shrinkage.[51] Another study using an Alzheimer's disease mouse model demonstrated that treatment with dasatinib + quercetin removed senescent cells from the brain and contributed to decreased neuroinflammation, lowered amyloid-beta load, and slowed cognitive decline.[52] These results suggest that senolytic compounds may hold promise for the treatment of neurodegenerative diseases in humans.

At the time of this writing, a phase 1 clinical trial is underway to test the safety of quercetin in combination with dasatinib in humans with early Alzheimer's disease.Source:

Quercetin and bone loss

Osteoporosis, or age-related bone loss, is a serious health problem, affecting more than 200 million people worldwide. In a series of experiments in mice, researchers established a causal role for senescent cells in bone loss with aging.[53] Furthermore, the authors of the study found that administering a combination of quercetin and dasatinib once per month cleared senescent cells, resulting in increased bone mass and strength.

Quercetin and pulmonary fibrosis

Idiopathic pulmonary fibrosis, or IPF, is an age-related chronic lung disease associated with the accumulation of senescent cells in the lungs. In a mouse IPF model, clearing senescent cells using a combination of quercetin and dasatinib improved lung function and overall health.[54]

Due to mounting preclinical evidence, the combination of quercetin and dasatinib is being tested in human clinical trials — initially to assess the safety and identify side effects, and then to determine efficacy.

A recent open-label pilot study in humans investigated the feasibility and safety of providing a senolytic agent to adults with IPF. The study involved 14 participants with stable IPF who received oral doses of dasatinib (100 milligrams) combined with quercetin (1,250 milligrams) administered intermittently three times a week over a period of three weeks. All participants completed the study and experienced some clinical improvements. Adverse events were mild and included gastrointestinal discomfort and headache. The participants showed improved physical function, assessed by how far they were able to walk in a six-minute walk test and other measures.[55]

This study revealed for the first time that administering a senolytic agent to humans is feasible and suggests that these compounds can relieve some of the dysfunction associated with an age-related disease. This was a small trial with no placebo control so these results are preliminary. However, the authors stated that their findings have encouraged them to proceed with larger clinical trials. While this research supports the preclinical evidence that clearing senescent cells mitigates age-related conditions, follow-up studies involving larger numbers of people are needed.

Kidney damage can occur due to risk factors such as diabetes, hypertension, and obesity. The authors of a study in mice demonstrated that senescent cells accumulate in the kidneys of obese animals with abnormal blood lipid levels. They proposed that this process is responsible for kidney damage. Mice were fed either standard chow or a high-fat diet to induce obesity. The authors observed that quercetin at 50 mg/kg/bw administered five days biweekly for 10 weeks cleared senescent cells and improved renal function in a mouse model of the disease.[56]

Further evidence that senescent cells trigger kidney damage was demonstrated in another mouse study. The authors of the study transplanted irradiated porcine kidney cells into the aortas of mice. After four weeks, the authors observed renal hypoxia and elevated plasma creatinine, indicative of renal injury in the treated mice.[57]

In an open-label phase 1 pilot study in which nine adults with diabetic kidney disease were given oral doses of quercetin (1,000  milligrams) and dasatinib (100 milligrams)  for three days, the study participants demonstrated reduced senescent cell burden in adipose tissue within 11 days compared to baseline. The participants exhibited fewer senescent cells in the blood, skin, and fat tissues. These preliminary findings demonstrate for the first time that senolytic drugs, including quercetin, can decrease senescent cells in humans.[58]

" In an open-label phase 1 study, nine adults with diabetic kidney disease were given oral doses of quercetin and dasatinib for three days, the study participants demonstrated reduced senescent cell burden in adipose tissue within 11 days compared to baseline. " Click To Tweet

While these results look promising, the authors of the study caution that the findings are preliminary and the field of senolytics is new. Negative effects may arise from large numbers of senescent cells dying and spilling their cellular waste into surrounding tissues. Moreover, senescent cells perform important cellular functions, such as seen in wound healing. This research is preliminary, was not placebo-controlled, and must be confirmed in larger trials. Based on the findings of these phase 1 trials, the Food and Drug Administration has approved Phase 2 trials for dasatinib/quercetin combination for IPF and diabetes-related kidney fibrosis.


Quercetin found in food occurs as glycosides — bound to a sugar molecule — while the supplemental form of quercetin usually occurs as an aglycone. After ingesting quercetin glycosides, beta-glucosidases, enzymes that cleave glucose bonds, remove the sugar component yielding quercetin aglycone. Quercetin aglycone can passively diffuse across the small intestine wall or be transported by the sodium/glucose cotransporter-1.[59] Once absorbed, quercetin undergoes extensive biotransformation by the liver to yield quercetin’s principal metabolites, chiefly, methylated, sulfated, and glucuronidated conjugates. As a result, the product delivered to cells is often markedly different from the original.[60]

Quercetin bioavailability and safety profile

Quercetin's bioavailability is low (approximately 1 percent uptake) due to quercetin's poor solubility and hydrophilic nature. It is likely influenced by a variety of factors, including dose, the presence of other foods or substances, and interindividual differences in metabolism due to the gut absorptive surface and commensal microbial populations. Enhanced delivery systems such as liposomes and phytosomes as well as dietary fat have been shown to improve quercetin bioavailability.

Liposomal delivery systems

A liposomal formulation of quercetin markedly reduced liver damage in rodents, whereas free quercetin was ineffective.[61] Evidence suggests that liposomal accumulation in the liver may serve as a slow-releasing reservoir of its cargo, enabling more continuous release and prolonging half-life.[62] Liposome-polymer complexes may further bolster the stability, bioavailability, and efficacy of quercetin.[63] [64]

Liposomes are artificial vesicles composed of one or more phospholipid bilayers that enclose an internal cavity capable of carrying hydrophilic substances. This bilayer structure closely resembles that of mammalian cell membranes, facilitating the liposomes' uptake into cells and eliciting greater effect. Because liposomes are biodegradable, biocompatible, non-toxic, and non-immunogenic, they are highly effective delivery systems for xenobiotics, including drugs and polyphenolic compounds such as quercetin.[65]

Phytosomal delivery systems

An industry-funded study in humans investigated the bioavailability of a food-grade lecithin-based phytosomal quercetin formulation versus free quercetin. Participants received one dose of phytosomal quercetin (either 250 milligrams or 500 milligrams) or free quercetin (500 milligrams). Phytosomal quercetin uptake was 10 to 17 times greater than free quercetin. [66]

Phytosomes are delivery systems that are structurally similar to liposomes. They are prepared by attaching a hydrophilic compound to a phospholipid bilayer (typically phosphatidylcholine, which is derived from lecithin). The attached compound is thus incorporated into the bilayer, promoting greater solubility and absorption.[67]

Dietary components

Dietary fat appears to influence quercetin uptake. In humans, co-ingestion of a high-fat food item (30 percent of total caloric content) with quercetin increased plasma quercetin levels by 32 percent compared to co-ingestion of the same, but low-fat, food.[68] Similarly, a study in animals found that co-ingestion of a medium- or long-chain triglyceride-rich chow with quercetin increased the bioavailability of quercetin by 38 percent and 12 percent, respectively, compared to co-ingestion of the animals' standard chow.[69]


Few adverse events have been reported in human studies of quercetin in the range of 500 to 1,000 milligrams per day.[70] However, few studies in humans have evaluated the long-term use of quercetin at doses greater than 1,000 milligrams per day. One study reported kidney toxicity in rats given high doses of quercetin, roughly equivalent to 140 grams for a person weighing 70 kilograms.[71]

Quercetin interferes with the activity of drug-metabolizing enzymes, altering the absorption of xenobiotics, including environmental contaminants and pharmaceutical drugs. Whereas quercetin impairs the activity of the cytochrome P450 enzymes CYP3A4 and CYP1A2, it increases the activity of other enzymes, including N-acetyltransferase, which mediates the deactivation of various drugs and carcinogens. Moreover, quercetin inhibits the activity of the P-glycoprotein transporter that facilitates the movement and elimination of some drugs, possibly altering their blood levels.

Quercetin has serious interactions with everolimus and topotecan — two drugs used in the treatment of cancer. Quercetin alters the metabolism of these drugs by inhibiting a key drug-metabolizing enzyme and decreasing the drugs' excretion rate. This can cause drug levels to increase and accumulate in non-target tissues.[72] [5] A study in pigs demonstrated a lethal interaction between the oral administration of quercetin 50 (mg/kg/bw) and digoxin (0.02 mg/kg/bw).[73] Moderate interactions may occur between quercetin and certain antibiotics and drugs such as prednisone.[5] Preclinical research suggests that quercetin may also interact with dietary supplements. For example, it increases the bioavailability of epigallocatechin gallate, or EGCG, a polyphenol found in green tea.[74]

Some in vitro research suggests that quercetin can act as a mutagen, causing DNA damage. However, in vitro studies are unable to account for the extensive metabolism that quercetin undergoes.[71] These cancer-causing effects were not observed in vivo in rodent studies.[70]

Quercetin appears to be well tolerated without reports of serious side effects.


Quercetin is a plant polyphenol found in a variety of fruits and vegetables and available as a dietary supplement. Quercetin has antioxidant, anti-inflammatory, and anti-aging properties that exert many effects on human health. It participates in a variety of biological processes and pathways and affects multiple organ systems. Even though much of the research on quercetin's effects on chronic diseases has been conducted in animals, some human trials have been conducted or are underway. Of particular interest is quercetin's ability to kill senescent cells when given in combination with dasatinib. A growing body of evidence supports the hypothesis that clearing senescent cells may treat and possibly reverse many diseases of aging. However, well-controlled clinical trials need to be conducted to evaluate whether senolytic compounds such as quercetin and dasatinib can contribute to healthspan and longevity. Quercetin is extensively metabolized by the liver and other organs after absorption and demonstrates poor bioavailability. Its safety profile is generally favorable, with only minor side effects reported. Quercetin may impact many facets of human health, and future research should determine if the preclinical findings translate to humans.

  1. ^ Quercetin: A flavonol with multifaceted therapeutic applications? Fitoterapia 106 (October 2015): 256–71.
  2. ^ Quercetin content in some food and herbal samples Food Chemistry 100, no. 2 (January 2007): 699–704.
  3. ^ Overviews of Biological Importance of Quercetin: A Bioactive Flavonoid Pharmacogn Rev 10, no. 20 (2016): 84–89.
  4. ^ Higher Antioxidant Activity, Total Flavonols, and Specific Quercetin Glucosides in Two Different Onion (Allium cepaL.) Varieties Grown under Organic Production: Results from a 6-Year Field Study Journal of Agricultural and Food Chemistry 65, no. 25 (June 2017): 5122–32.
  5. ^ a   b   c Quercetin: A flavonol with multifaceted therapeutic applications? Fitoterapia 106 (October 2015): 256–71.
  6. ^ Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models Atherosclerosis 218, no. 1 (September 2011): 44–52.
  7. ^ Impact of quercetin on systemic levels of inflammation: a meta-analysis of randomised controlled human trials International Journal of Food Sciences and Nutrition 71, no. 2 (June 2019): 152–63.
  8. ^ Effects of supplementation with quercetin on plasma C-reactive protein concentrations: a systematic review and meta-analysis of randomized controlled trials European Journal of Clinical Nutrition 71, no. 9 (May 2017): 1033–39.
  9. ^ The effects of quercetin supplementation on lipid profiles and inflammatory markers among patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials Critical Reviews in Food Science and Nutrition 60, no. 11 (April 2019): 1855–68.
  10. ^ Nanotechnological Innovations Enhancing the Topical Therapeutic Efficacy of Quercetin: A Succinct Review Current Drug Delivery 17, no. 4 (June 2020): 270–78.
  11. ^ Quercetin downregulates NADPH oxidase, increases eNOS activity and prevents endothelial dysfunction in spontaneously hypertensive rats J. Hypertens. 24, no. 1 (January 2006): 75–84.
  12. ^ Effects of daily quercetin-rich supplementation on cardiometabolic risks in male smokers Nutr Res Pract 5, no. 1 (February 2011): 28–33.
  13. ^ Does Quercetin Improve Cardiovascular Risk factors and Inflammatory Biomarkers in Women with Type 2 Diabetes: A Double-blind Randomized Controlled Clinical Trial Int J Prev Med 4, no. 7 (July 2013): 777–85.
  14. ^ Effects of Quercetin on Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials J Am Heart Assoc 5, no. 7 (July 2016).
  15. ^ Digitoxin metabolism by rat liver microsomes Biochem. Pharmacol. 24, no. 17 (September 1975): 1639–41.
  16. ^ Flavonols reduce aortic atherosclerosis lesion area in apolipoprotein E deficient mice: A systematic review and meta-analysis PLOS ONE Edited by Kottarappat N Dileepan. 12, no. 7 (July 2017): e0181832.
  17. ^ Effect of Flavonoids on Oxidative Stress and Inflammation in Adults at Risk of Cardiovascular Disease: A Systematic Review Healthcare (Basel) Healthcare (Basel) 4, no. 3 (September 2016).
  18. ^ Quercetin transiently increases energy expenditure but persistently decreases circulating markers of inflammation in C57BL/6J mice fed a high-fat diet Metab. Clin. Exp. 57, no. 7 Suppl 1 (July 2008): 39–46.
  19. ^ Chronic dietary intake of quercetin alleviates hepatic fat accumulation associated with consumption of a Western-style diet in C57/BL6J mice Molecular Nutrition & Food Research 55, no. 4 (December 2010): 530–40.
  20. ^ Quercetin reduces obesity-associated ATM infiltration and inflammation in mice: a mechanism including AMPK1/SIRT1 Journal of Lipid Research 55, no. 3 (January 2014): 363–74.
  21. ^ Quercetin Ameliorates Cardiovascular, Hepatic, and Metabolic Changes in Diet-Induced Metabolic Syndrome in Rats The Journal of Nutrition 142, no. 6 (April 2012): 1026–32.
  22. ^ Quercetin accelerated cutaneous wound healing in rats by increasing levels of VEGF and TGF-β1 Indian J. Exp. Biol. 54, no. 3 (March 2016): 187–95.
  23. ^ The impact of quercetin on wound healing relates to changes in αV and β1 integrin expression Exp. Biol. Med. (Maywood) Exp. Biol. Med. (Maywood) 242, no. 14 (August 2017): 1424–31.
  24. ^ An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA Dev. Cell 31, no. 6 (December 2014): 722–33.
  25. ^ A comprehensive evidence-based review on the role of topicals and dressings in the management of skin scarring Arch. Dermatol. Res. 307, no. 6 (August 2015): 461–77.
  26. ^ Evidence-Based Scar Management Plastic and Reconstructive Surgery 138 (September 2016): 165S–178S.
  27. ^ Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture PLoS Pathog. 6, no. 11 (November 2010): e1001176.
  28. ^ The Therapeutic and Prophylactic Potential of Quercetin against COVID-19: An Outlook on the Clinical Studies, Inventive Compositions, and Patent Literature Antioxidants 11, no. 5 (April 2022): 876.
  29. ^ Quercetin supplementation and upper respiratory tract infection: A randomized community clinical trial Pharmacol. Res. 62, no. 3 (September 2010): 237–42.
  30. ^ The Effect of Quercetin on Inflammatory Factors and Clinical Symptoms in Women with Rheumatoid Arthritis: A Double-Blind, Randomized Controlled Trial J Am Coll Nutr 36, no. 1 (January 2017): 9–15.
  31. ^ The Effects of Quercetin Supplementation on Eccentric Exercise-Induced Muscle Damage Nutrients 11, no. 1 (January 2019): 205.
  32. ^ Effects of quercetin supplementation on endurance performance and maximal oxygen consumption: a meta-analysis Int J Sport Nutr Exerc Metab 23, no. 1 (February 2013): 73–82.
  33. ^ Quercetin increases brain and muscle mitochondrial biogenesis and exercise tolerance Am. J. Physiol. Regul. Integr. Comp. Physiol. 296, no. 4 (April 2009): R1071–1077.
  34. ^ Oral quercetin supplementation hampers skeletal muscle adaptations in response to exercise training Scandinavian Journal of Medicine & Science in Sports 24, no. 6 (October 2013): 920–27.
  35. ^ Quercetin supplementation does not enhance cerebellar mitochondrial biogenesis and oxidative status in exercised rats Nutrition Research 35, no. 7 (July 2015): 585–91.
  36. ^ The combination of oral quercetin supplementation and exercise prevents brain mitochondrial biogenesis Genes & Nutrition 9, no. 5 (August 2014).
  37. ^ Exercise-Induced Oxidative Stress and the Effects of Antioxidant Intake from a Physiological Viewpoint Antioxidants 7, no. 9 (September 2018): 119.
  38. ^ The compelling link between physical activity and the body s defense system Journal of Sport and Health Science 8, no. 3 (May 2019): 201–17.
  39. ^ Effect of Vitamin C Supplements on Physical Performance Current Sports Medicine Reports 11, no. 4 (2012): 180–84.
  40. ^ The serial cultivation of human diploid cell strains Exp. Cell Res. 25 (December 1961): 585–621.
  41. ^ a   b Cellular senescence: when bad things happen to good cells Nature Reviews Molecular Cell Biology 8, no. 9 (September 2007): 729–40.
  42. ^ The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs Aging Cell 14, no. 4 (April 2015): 644–58.
  43. ^ Cellular Senescence: A Translational Perspective EBioMedicine 21 (July 2017): 21–28.
  44. ^ Human Obesity Induces Dysfunction and Early Senescence in Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells Frontiers in Cell and Developmental Biology 8 (March 2020).
  45. ^ Targeting senescent cells enhances adipogenesis and metabolic function in old age eLife 4 (December 2015).
  46. ^ a   b Senolytics improve physical function and increase lifespan in old age Nature Medicine 24, no. 8 (July 2018): 1246–56.
  47. ^ Naturally occurring p16Ink4a-positive cells shorten healthy lifespan Nature 530, no. 7589 (February 2016): 184–89.
  48. ^ Genomes of replicatively senescent cells undergo global epigenetic changes leading to gene silencing and activation of transposable elements Aging Cell 12, no. 2 (April 2013): 247–56.
  49. ^ Aging, Cell Senescence, and Chronic Disease JAMA 320, no. 13 (October 2018): 1319.
  50. ^ Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice Aging Cell 15, no. 5 (August 2016): 973–77.
  51. ^ Tau protein aggregation is associated with cellular senescence in the brain Aging Cell 17, no. 6 (October 2018): e12840.
  52. ^ Senolytic therapy alleviates A-associated oligodendrocyte progenitor cell senescence and cognitive deficits in an Alzheimer’s disease model Nature Neuroscience 22, no. 5 (April 2019): 719–28.
  53. ^ Targeting cellular senescence prevents age-related bone loss in mice Nature Medicine 23, no. 9 (August 2017): 1072–79.
  54. ^ Cellular senescence mediates fibrotic pulmonary disease Nat Commun 8 (February 2017): 14532.
  55. ^ Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study EBioMedicine 40 (February 2019): 554–63.
  56. ^ Increased renal cellular senescence in murine high-fat diet: effect of the senolytic drug quercetin Translational Research 213 (November 2019): 112–23.
  57. ^ Transplanted senescent renal scattered tubular-like cells induce injury in the mouse kidney Am. J. Physiol. Renal Physiol. 318, no. 5 (May 2020): F1167–F1176.
  58. ^ Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease EBioMedicine 47 (September 2019): 446–56.
  59. ^ Safety Aspects of the Use of Quercetin as a Dietary Supplement Mol Nutr Food Res 62, no. 1 (January 2018).
  60. ^ A minireview of quercetin: from its metabolism to possible mechanisms of its biological activities Critical Reviews in Food Science and Nutrition , November 2019, 1–14.
  61. ^ DOI: 0.1080/15227950290097615
  62. ^ DOI: 10.1002/adhm.202100639
  63. ^ DOI: 10.1039/C3TB21238F
  64. ^ Quercetin in anti-diabetic research and strategies for improved quercetin bioavailability using polymer-based carriers a review RSC Advances 5, no. 118 (2015): 97547–62.
  65. ^ DOI: 10.1186/s12645-019-0055-y
  66. ^ 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, no. 2 (October 2018): 169–77.
  67. ^ DOI: 10.1016/B978-0-12-815673-5.00010-6
  68. ^ DOI: 10.1016/j.jnutbio.2014.10.008
  69. ^ DOI: 10.1017/BJN20061953
  70. ^ a   b Safety Aspects of the Use of Quercetin as a Dietary Supplement Molecular Nutrition & Food Research 62, no. 1 (December 2017): 1700447.
  71. ^ a   b A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties Food and Chemical Toxicology 45, no. 11 (November 2007): 2179–2205.
  72. ^ Hyaluronic Acid Nanohydrogel Loaded With Quercetin Alone or in Combination to a Macrolide Derivative of Rapamycin RAD001 (Everolimus) as a New Treatment for Hormone-Responsive Human Breast Cancer Journal of Cellular Physiology 232, no. 8 (March 2017): 2063–74.
  73. ^ Lethal quercetin-digoxin interaction in pigs Life Sciences 74, no. 10 (January 2004): 1191–97.
  74. ^ Studies on the effects of oral administration of nutrient mixture, quercetin and red onions on the bioavailability of epigallocatechin gallate from green tea extract Phytotherapy Research 24, no. S1 (July 2009): S48–S55.

Topics related to Aging

view all
  • Epigenetic aging clocks
    Epigenetic clocks are predictors of biological age based on alterations in an individual's DNA methylation profile.
  • Aerobic exercise
    Aerobic exercise, physical activity that increases breathing and heart rate, promotes cardiovascular, brain, and whole-body health.
  • Breast milk and breastfeeding
    Breast milk is a complex, dynamic fluid that contains nutritional and non-nutritional components that positively influence an infant's development. Breastfeeding benefits both infants and mothers.
  • Sirtuins
    Sirtuins play a key role in healthspan and longevity by regulating a variety of metabolic processes implicated in aging.
  • Hallmarks of aging
    The hallmarks of aging are observable biological patterns of dysfunction that accrue in a biological organism over time.
  • Zinc
    Zinc is an essential nutrient that influences growth and development and plays critical roles in immune function, protein synthesis, wound healing, DNA synthesis, and cell division.