The antioxidant quercetin is sometimes called the “master flavonoid.” People say it’s one of the best natural antihistamines — allegedly, one that can stabilize mast cells and reduce inflammation. Is any of this true? Read to understand what the latest science says about quercetin and whether there is any way to overcome its poor bioavailability.
What is Quercetin?
Most people have heard of flavonoids, plant-based antioxidant pigments that are being touted for many alleged health benefits. Flavonoids give plants their color and belong to the class of polyphenols. Polyphenols became a hot topic recently when some studies suggested their benefits in preventing heart disease, cancer, and other chronic diseases [1, 2].
Snapshot
Proponents
- May be anti-inflammatory
- Alleged natural antihistamine
- May increase antioxidant protection
- Found in fruits, nuts, and herbs
Skeptics
- Poor bioavailability
- May alter thyroid function
- Inhibits COMT
- Unknown long-term safety
- Few large-scale clinical trials
Purported Benefits of Quercetin
Possibly Ineffective For:
1) Athletic Endurance
The majority of studies suggest that taking quercetin before exercise does not decrease fatigue or improve exercise ability. Therefore, quercetin is likely ineffective for improving athletic performance.
In clinical trials of over 200 people in total, the effects of quercetin on endurance exercise capacity (VO2 max and performance) was trivial [3, 4].
In two smaller and less reliable studies, quercetin (1000 mg/day) increased endurance and reduced fatigue (in 12 untrained people and 10 young men after resistance training) [5, 6].
Insufficient Evidence For:
The following purported benefits are only supported by limited, low-quality clinical studies. There is insufficient evidence to support the use of quercetin for any of the below listed uses.
Remember to speak with a doctor before taking quercetin supplements. Quercetin should never be used as a replacement for approved medical therapies.
2) Inflammation
There is insufficient evidence to support the use of quercetin for inflammatory disorders.
Quercetin may decrease inflammatory cytokines that can damage tissues in humans [7, 8].
There’s limited scientific ground for using quercetin to reduce prostate inflammation and enlargement. In an initial small study, it reduced symptoms of prostate inflammation in men by 75% [9].
In the next study of 30 men, quercetin (1000 mg/day) reduced prostate inflammation and pain in 67% of them after 1 month. Then 17 men also received bromelain and papain as an add-on to enhance quercetin absorption, along with palmetto and cranberry. This combination improved symptoms in over 80% of the men [10].
In cells, quercetin decreases the release of the following inflammatory compounds: MCP-1, IL-6, and IL-8 [11].
Quercetin blocks the production of prostaglandins, key mediators of the inflammatory response. It also blocks, COX-2, an inflammatory enzyme NSAID drugs target [12, 13].
3) Metabolic Health
There is insufficient evidence to suggest that quercetin should be used to improve metabolic health.
Quercetin (1000 mg/day) improved the metabolic profile in 78 obese women with PCOS in one clinical trial. It was used over 12 weeks and reduced an obesity marker (resistin), and well as testosterone and LH [14].
4) Arthritis
Evidence is lacking to support the use of quercetin for rheumatoid arthritis. Larger clinical trials are needed. Studies conducted so far had mixed results.
In one study, people with Rheumatoid Arthritis who consumed lots of raw berries, fruits, vegetables, nuts, roots, seeds, and sprouts rich in Quercetin and other antioxidants had fewer symptoms [15].
Quercetin supplements (500 mg/day) had no effect on some inflammatory markers (CRP) but did reduce others (TNF-alpha and IL-6) in an 8-week study of 51 women. But in a later 8-week follow up study in 50 women, the same dose did reduce joint stiffness, morning pain, after-activity pain and the inflammatory marker TNF-alpha [16, 17].
In a cellular study, Quercetin triggered the death of inflammatory joint cells that contribute to the development of rheumatoid arthritis. In another study, it also stopped these cells from dividing and prevented neutrophil activation, which worsens the autoimmune response [18, 19+].
5) Heart Health & Blood Flow
Insufficient evidence is available to say that quercetin improves heart health or blood. The published research is encouraging, but large-scale studies are lacking.
Quercetin (730/day) lowered blood pressure in a trial of 41 people with high blood pressure after 28 days [20].
In a trial of 72 women with type 2 diabetes, Quercetin (500 mg/day) reduced systolic blood pressure after 10 weeks [21].
Lower dose quercetin (100 mg/day) from onion peel extract improved blood lipid profiles, glucose, and blood pressure in a study of 92 smokers. It reduced total and “bad” LDL cholesterol while increasing “good” HDL cholesterol, overall improving heart health [22].
In a clinical trial of 10 healthy men, a combination quercetin supplement (200 mg quercetin with EGCG and epicatechin) increased nitric oxide status. Nitric oxide helps expand the blood vessels to deliver more blood to the body. It also reduced endothelin-1, which narrows blood vessels and counteracts nitric oxide [23].
In one observational study of 120 healthy people, a multivitamin supplement with quercetin increased blood quercetin levels, reduced homocysteine, and GGT, which are important for heart health and circulation [24].
Scientists are exploring whether quercetin supplements can partially protect people exposed to high levels of oxidative stress (such as cigarette smokers) from heart disease [25].
6) Immune Defense
Based on the existing evidence, quercetin may not have an effect on immune defense. More research is needed.
In a study of ~1000 people, Quercetin (1000 mg/day) reduced the number of sick days and the severity of common cold symptoms in physically-fit people 40 or older [26].
Endurance athletes are more likely to catch a cold since they frequently stretch their bodies to exhaustion. Quercetin (100 mg/day) reduced the incidence of upper respiratory infections such as the common cold in a trial of 40 trained athletes. It was given after 3 days of intense exercise over the 2-week exercise recovery period [27].
However, quercetin alone (1000 mg/day) for three weeks before, during, and for two weeks after the 160-km Western States Endurance Run didn’t lower flu incidence in another study [28].
7) Post-Exercise Recovery
In one trial, Quercetin (1000 mg/day) reduced inflammation in a trial of 30 cyclists following heavy training. It had a stronger effect combined with other antioxidants and anti-inflammatories: EGCG, isoquercetin, EPA, and DHA [29].
Quercetin (1000 mg/day) reduced post-exercise inflammation and oxidative stress after 2 weeks in young untrained men [30].
8) Ulcers
There are not enough clinical data to rate the effectiveness of quercetin for ulcers.
In a trial of 40 men, quercetin applied directly to mouth ulcers relieved pain and completely healed the ulcers in half of the cases within 7–10 days [31].
Quercetin is being researched against stomach ulcers, Helicobacter pylori, and acid reflux in animals and cells [8].
Lacking Evidence For:
No valid evidence supports the use of quercetin for any of the conditions listed in this section.
Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts.
However, the studies listed below should not be interpreted as supportive of any health benefit.
Quercetin should not be used for any of the conditions described below due to a complete lack of safety and efficacy data in humans.
9) Diabetes
Mice fed a Quercetin-rich diet had lower blood glucose levels and HBA1c. Quercetin may block the enzymes that degrade complex sugars in the gut after meals. As a consequence, less glucose is absorbed from food [32].
In rats with type 1 diabetes, Quercetin lowered blood sugar levels [33].
Quercetin also improved insulin levels in diabetic mice and reduced the activity of liver and pancreas genes that can trigger diabetes [34].
In obese rats, Quercetin supplementation improved insulin resistance [35].
Quercetin increases glucose uptake into fat cells by increasing the number and activity of glucose transporters. It also sensitizes a pathway that controls insulin release in response to glucose (ERK1/2) (GLUT4) [36, 37, 38].
One cell study analyzed the effects of ten compounds from berries on glucose uptake. Two forms of Quercetin had the strongest effect on glucose uptake into tissues via the AMPK pathway (sugar-bound Quercetin-3-O-glycoside and the free Quercetin aglycone) [39, 40].
Quercetin might also block the NF-kb pathway [41].
10) Brain Health
Scientists are studying if quercetin can protect brain cells from oxidative stress [42].
It may shield the brain from toxic substances, according to studies in mice. It increased an antioxidant enzyme, superoxide dismutase (SOD) and decreased markers of oxidative stress. It also improved cognition, learning, and memory [43].
In mice, it also had an epigenetic effect: increasing the expression of genes that boost the function of existing brain cells and regenerate old or damaged ones [43].
Flavonoids, including quercetin, block inflammatory molecules in the brain [44].
Additionally, quercetin reversed cognitive deficits in aged mice with Alzheimer’s disease. It also prevented disease worsening but had the strongest effect in the early-middle stages of the disease [45].
Antipsychotics used to treat schizophrenia can cause movement disorders as a side effect, which are similar to Parkinson’s. Quercetin reduced these side effects in mice given antipsychotics [42].
11) Leaky Gut
According to some theories, chronic stress can over-activate mast cells in the gut, which leads to increased inflammation and permeability of the gut lining (“leaky gut”) [46, 47].
Certain scientists hypothesize that quercetin has dual action: it might help rebuild a healthy gut barrier and prevent mast cells from flooding the gut with histamine. Their theories remain unproven, however [46, 47].
In rat studies, quercetin blocked histamine release and stabilized gut mast cells. This may help both prevent and heal leaky gut [48].
Quercetin reversed “leaky gut” in mice and helped rebuild the gut barrier. Once the gut lining was restored, inflammation decreased as well [49].
In another study, it tightened the junctions between gut cells in a cellular study. It increased the activity of genes that make the gut lining and reduce gut inflammation, which may help strengthen the gut barrier and prevent unwanted food particles from entering the bloodstream [50].
12) Anti-Aging
Scientists think that quercetin might be a “senolytic,” a natural compound that may stop the aging process. In studies on human skin cells, it eliminated harmful, aging senescent cells [8+].
Quercetin extended the lifespan and increased stress resistance in worms. Another study suggested that it increases the ability of worms to handle stress while increasing their average lifespan by 15% [51, 52].
However, it is unclear how these cellular and worm studies translate to humans. A recent study found that Quercetin does not extend the lifespan of animals, which should serve as a reminder that “benefits” in cell culture often don’t translate to living beings [53].
13) Obesity
In mice, Quercetin supplementation reduced body weight by nearly 40%, reduced inflammatory cytokines increased in obesity, and boosted fat burning. It also increased anti-inflammatory defense (IL-10) [54].
Quercetin reduced weight gain caused by a high-fat diet and improved insulin sensitivity and glucose tolerance in mice [55].
In rats, it reduces obesity-triggered skeletal muscle wasting by blocking inflammatory receptors and their activity [56].
High dose Quercetin reduced blood glucose levels, improved blood lipids and reduced high blood pressure in obese rats. Quercetin enhanced the sensitivity of fat tissues to glucose (via GLUT4 translocation and AKT signaling), which causes fats to take more glucose from the blood and use it [35, 55].
In cell studies, it reduced fat accumulation and inflammation from obesity [54].
Quercetin turned off obesity genes linked to inflammation (AMPK and MAPK pathways), which stops tissues from storing new fats and triggers the destruction of existing fat cells [57].
14) Cancer Prevention Research
Quercetin has not been shown to treat or prevent cancer.
Scientists are researching whether quercetin and other flavonoids from fruits and vegetables may contribute to cancer prevention.According to some studies, people who eat more fruits and vegetables tend to have a lower risk of certain types of cancer [58].
One observational study on almost 1,000 people suggested a link between frequent intake of quercetin-rich foods and lower risk of developing lung cancer. The association was stronger in those under 50 years of age [59].
However, both studies deal only with associations. Proper clinical data are still lacking
Similarly, smokers who consumed lots of antioxidant-rich phenols were thought to be slightly better protected against bladder cancer in one study. The authors emphasized that their findings need to be verified and explored further [60].
Quercetin lowers TNF-a and, which, according to some hypotheses, may contribute to cancer prevention; TNF-a encourages the growth and spreading of most tumor cells. In fact, mice with TNF-a deficiencies are resistant to skin cancer. Quercetin increased the lifespan of mice with leukemia [61, 62].
Cellular studies are investigating the potential mechanisms of TNF-a-lowering flavonoids, including quercetin. Quercetin was studied in the following types of cells [63]:
- Colon cancer cells (blocking the NF-κB pathway) [64].
- Leukemia cells (inhibiting Cox-2 expression and initiating apoptosis) [65, 58].
- Brain and liver cancer cells [66, 67].
- Breast cancer cells [62].
However, many substances have anti-cancer effects in cells, including downright toxic chemicals like bleach. This doesn’t mean that they have any medical value. In fact, most substances (natural or synthetic) that are researched in cancer cells fail to pass further animal studies or clinical trials due to a lack of safety or efficacy.
Thus, much more research is needed before the effects of quercetin on cancer in people are determined [68].
15) Histamine Release
Many people with histamine issues claim that quercetin helped them, especially those who are TH2-dominant. No valid evidence backs them up.
Only cell-based and animal studies have been carried out. Ongoing research efforts should determine if quercetin can:
- Reduce histamine and other inflammatory substances like leukotrienes, and prostaglandins [2].
- Reduce inflammation in cells and/or turn off the histamine receptor gene (H1R) [69].
Until further studies are published, the effects of quercetin on histamine release remain unknown.
16) Bacterial Infections
Quercetin was studied against various types of bacteria in test tubes (Staphylococcus, S. aureus, H. Pylori) [70, R, R].
It blocked the growth of oral bacteria in cellular studies. Quercetin may block an important enzyme bacteria need to survive (DNA gyrase) [71, 72].
17) Allergies & Asthma
People say quercetin helps with Th2 dominance, but research is lacking. We can’t draw any conclusions from the existing animal and cell-based studies.
Quercetin relaxed smooth muscles that line the airways in a tissue study, which improves airway flow [73].
Lactose, eggs, peanuts, fish, wheat, shellfish, tree nuts, and soy can all trigger an immunoglobulin E (IgE) allergic responses [74].
Quercetin reduced allergies and balanced the immune response in cellular and animal studies [75, 76].
Mast cells are activated during an allergic response or in people with mast cell activation syndrome. Overactive mast cells promote inflammation by releasing molecules such as histamine, leukotrienes, cytokines, and other harmful products. Quercetin blocks mast cell activation in cells [8+].
Some people with hay fever have an over-expression of the histamine H1 receptor (H1R) gene. Increased expression of this gene has been linked with more severe allergic symptoms. Quercetin may reduce the expression of this gene [69].
18) Liver Health
Quercetin given before toxic amounts of alcohol protected the liver of rats against oxidative stress. It neutralized harmful products of fat breakdown and increased the production of the master antioxidant Glutathione [77].
Quercetin protected the liver, limited damage and oxidative stress in rats exposed to toxins (aflatoxin) [78].
Acetaminophen can cause serious liver damage in high doses, and overdoses in humans are not rare. Quercetin can reduce liver damage from acetaminophen by neutralizing free radicals. It protected both the kidneys and liver in rats and improved mitochondria health [79].
In rats with liver damage, Quercetin improved liver health, decreased liver scarring, oxidative stress and DNA damage [80].
Quercetin protected against obesity-induced fatty liver disease in mice by activating the mitochondria and improving energy use in the liver [81].
19) Kidney Health
In rats given the chemotherapy drug cisplatin, quercetin protected the kidney tissue [82].
Additionally, it reduced kidney damage and restored kidney antioxidant enzymes in another rat study [83].
However, these studies used quercetin injections, which have good bioavailability.
20) Sexual Function
Oxidative stress is a primary cause of the inability to get or maintain an erection, also known as erectile dysfunction. Quercetin improved erectile dysfunction by reducing levels of oxidative stress and increasing blood-vessel-relaxing nitric oxide in diabetic mice [84].
21) Eye Health
Quercetin may act on vision pathways (oxidative stress, glycation, and cell signaling) [85].
In rats with cataracts, it reduced eye damage and enhanced lens clarity [86].
Retinal cells found at the back of the eyes act as light receptors and play an important role in setting the color, resolution, and brightness of your vision. Quercetin had a protective effect on retinal cells and increased their survival [87, 88].
Limitations and Caveats
Most of the studies mentioned here were done in animals, although some clinical trials have been carried out. All of the listed potential benefits would rely on quercetin being absorbed. Poor absorption and bioavailability of quercetin is a major issue.
Further Reading
Takeaway
Quercetin is a common antioxidant flavonoid found in many fruits and vegetables. It is believed to have an important role in general human health, including in regulating inflammation, metabolism, blood flow, immune function, exercise recovery, and more.
Animal research suggests a very broad role for quercetin, including for the brain, gut, and as natural antihistamine. However, few clinical trials have been carried out.
Based on the exisiting data, quercetin probably doesn’t improve athletic performance. There is not enough reliable evidence to rate its effectieveness for any other purported benefit.
