Introduction

Quercetin is marketed as an ‘ergogenic’ or an agent that enhances physical performance. Needless to mention, the promise of ergogenic benefits is of great interest to many people. Me included. To be honest, I would love to add another few hours to my day by moving faster than I currently do. A little multi-tasking at warp speed would be quite nice.

In addition, quercetin is promoted as having cardiac, analgesic, anti-cancer and skin rejuvenating effects.

This sounds so exciting, I can’t decide whether I should try to get an infusion of quercetin  (stat) or maybe I should order a swimming pool of quercetin that I can dive into.

Or maybe, I should slow down to speed up and actually check the data on quercetin?

What Actually Is Quercetin?

Quercetin (3, 3′,4′,5,7-pentahydroxyflavone) is described as the great representative of polyphenols, flavonoids, and flavonols in nature. Quercetin is a natural flavonoid which is found in many vegetables and fruits.

Quercetin is pronounced ‘kwer- set-in’. If in doubt, you can even find transparent looking You Tubers who will teach you how to pronounce this word. (Maybe those You Tubers might consider actually taking some quercetin to try to offset the effects of living online).

Some people use the terms flavonoids and flavonols interchangeably but there are some distinctions between the two words.

Flavonoids are a group of plant metabolites or pigments that are generally believed to offer a range of health benefits. Technically speaking, flavanols are one of the five subgroups of flavonoids. What makes a flavonoid qualify as a card-carrying member of the flavonol class? Entry into the flavonol club requires the presence of two hydroxylated benzene rings which are called ring A and ring B. (Very original).

Flavonols are sub-classified based on the number and type of substitutions on the B ring. Quercetin has two hydroxyl rings at position 3 and 4 of the B ring. Hence the  3′,4′ part of the chemical name of quercetin which is 3, 3′,4′,5,7-pentahydroxyflavone.

Quercetin is both a flavonoid and a flavonol. There are different forms of quercetin which is something that becomes important as we move through interpreting the research on quercetin.

Quercetin glycoside is the primary formulation found in nature and involves quercetin linked to sugar moieties such as glucose or rutinose. Quercetin also less commonly is found as quercetin aglycone (a non-sugar compound remaining after replacement of the glycosyl group from a glycoside by a hydrogen atom). Quercetin is essentially insoluble in water.

Quercetin aglycone is absorbed in the stomach and small intestine (1). Neither quercetin glycoside nor rutinoside are absorbed in the stomach. Quercetin glucoside is absorbed in the small intestine while quercetin rutinoside is absorbed in the large intestine with the help of the gut microbiota.

The overall bioavailability of quercetin is low and varies from individual to individual. Bioavailability refers to the percentage of an oral dose that is absorbed.  Ranges of bioavailability for quercetin vary from 6% to 44%. The figure of 44% is thought to be an overestimation as this involved the dissolving the quercetin in alcohol which would not be standard practice and as mentioned above, quercetin is poorly water soluble.

Differences in vitamin C status may contribute to variability between subjects in the absorption of quercetin (2). People with lower vitamin C levels may have better absorption of quercetin as compared to their vitamin C replete counterparts.

Quercetin is also better absorbed as part of food as opposed to a supplement (3).

Just to make things a little more complicated, there are other forms of quercetin glycoside (quercetin arabinoside and quercetin galactose) and some quercetin glucosides are deglycosylated to quercetin prior to absorption. Who cares you might ask?

The take-home message here is that quercetin is not just a single molecular compound with a single, simple and highly predictable metabolic pathway in the body. Nature has devised all sorts of quercetin clones and lookalikes to keep things interesting.

The daily intake of quercetin in the standard American diet is approximately 15mg.

As part of the cellular matrix of plants and vegetables, flavonoids need to be released by chewing and then further processed by the digestive enzymes and/or gut microbiota (4).

The quercetin content of food varies depending on the cultivation conditions and possibly light exposure.

Here are the typical quercetin contents(mg) per 100mg of selected foods:

  • Red lettuce 40.27
  • Chilli pepper 32.59
  • CranberriesCranberries 17.34
  • Red onion 17.22
  • Tomato 5.56
  • Broccoli 4.25
  • Apple 2.47

The issue of light exposure is interesting. Under stressful conditions plants, accumulate flavonoid pigments such as quercetin to attenuate the response to UV radiation.

As quercetin is a photoprotector in plants, quercetin has also been proposed as a sunscreen. A 2012 study set out to establish whether quercetin was light stable and found that the dose of light that would be required to destroy quercetin is very high and that photodegradation of quercetin is not a significant concern (5).

There are over 600 quercetin products for sale on Amazon with 500mg of quercetin costing on average 20 cents.

Is There Any Research?

There are 15,807 publications on quercetin which include 233 clinical trials. To put this into context, flavonoids have over 100,000 publications including over 38,000 human clinical trials.

The glass half empty crew will look at these figures and complain that quercetin is poorly represented in the flavonoid research portfolio. The glass half full crew would compare quercetin to the other key flavonol, kaempferol, which has 4366 publications and 24 human clinical trials.

Does it Relieve Pain?

A 2015 study entitled ‘Comparison of shock wave therapy and nutraceutical composed of EchinaceaEchinacea Angustifolia, alpha lipoic acid, conjugated linoleum acid and quercetin in patients with carpal tunnel syndrome’ sounded interesting but was very disappointing (12).

The first hint of a problem came in the introduction when the study team never mentioned quercetin at all as part of the study design. Why was this? In fact, it turned out that 50mg of quercetin was part of the formulation that they were using and was not really considered as a player by the study team – just a passenger in the formulation that they used. It is so disappointing to find an article and think that it will yield useful information and then to find out that it is a non-player.

 A randomized, double-blind, placebo-controlled study published last year evaluated the effect of quercetin (500mg/day) versus placebo on rheumatoid arthritis for eight weeks (13).

Quercetin supplementation significantly reduced early morning stiffness, morning pain, and after-activity pain. The study showed a statistically significant reduction in levels of TNF-alpha but a non-statistically significant effect on the CRP. It is hard to know if quercetin is acting as an analgesic or an anti-inflammatory in this study.

Bottom Line

There is no proof that quercetin can function as a general analgesic.

Does Quercetin Reduce Inflammation & Allergies?

There is significant interest in the potential anti-inflammatory effects of quercetin.

A study published last year in the Journal of Functional Food evaluated the anti-inflammatory and antioxidant effects of quercetin and its derivatives (6). Investigators from Serbia studied a range of commercial quercetin products in addition to locally grown onions using accepted tests for antioxidant potential (DPPH, FRAP, and LP) and tests for anti-inflammatory potential (COX-1 and LOX).

They found that both the parent quercetin and its metabolites exhibited potent antioxidant and anti-inflammatory potential. The authors concluded that quercetin metabolites (and not just quercetin) should be factored into any considerations of biological activity.

There is particular interest in the possibility that quercetin has anti-allergic properties.

A study in guinea pigs showed that quercetin reduced airway hypersensitivity and relaxed the bronchial airways (7).

Quercetin exhibits similar anti-allergic potential as a Chinese herbal formula (Food Allergy Herbal Formula) and this Chinese formula has been shown to block peanut anaphylaxis in mouse models (8).

This has led some researchers to question as to whether quercetin may be the active agent (or one of the active agents) in the popular Chinese remedy?

A 2010 study in rats found that quercetin prevented peanut allergic reactions (9).

I have to clarify this. These are guinea pig and rat studies. Scientific speculation is great but has no role in peanut allergy.  Peanut allergy can be fatal and there is nothing to suggest that people with peanut allergy can relax their guard and take quercetin. Nothing.

Bottom Line

There is no human clinical trial data to support a role for quercetin in inflammation or allergy relief.

Does It Improve Heart Health?

There are two important studies relating to quercetin and cardiac health

A multi-center research team carried out a comprehensive meta-analysis of randomized controlled trials of quercetin on BP (10).

The meta-analysis was based on 7 trials comprising 9 treatment arms (587 patients). The results of the meta-analysis showed a statistically significant effect of quercetin supplementation on the reduction of BP, possibly limited to, or greater with dosages of >500 mg/day.The effect was modest with reductions in BP of the order of  -2mmHg for diastolic blood pressure and -3mmHg for systolic blood pressure.

A meta-analysis published last year looked at the effects of quercetin on lipids (11).

A total of five randomized controlled trials totaling 442 subjects (221 in the quercetin and 221 in the control group) were included in the meta-analysis. The study team found that there is no evidence to suggest any clinically relevant effect of quercetin supplementation on plasma lipids, apart from a significant reduction of triglycerides at doses above 50 mg/day.

 Bottom Line

Quercetin has a modest effect on lowering blood pressure and lowers triglycerides which may contribute to improving cardiac health in some patients.

Does It Improve Endurance?

A 2010 study from South Carolina set out to establish whether quercetin could enhance maximal aerobic capacity and delay fatigue in healthy but untrained volunteers (14). The study was small and only involved 12 volunteers who either received 7 days of quercetin 500mg in Tang or just regular Tang.

Tang is that sugary powdered drink that was made famous when NASA sent Tang on space missions. The study was a randomized, double-blind, placebo-controlled, cross-over study design.

Quercetin in Tang was associated with a small (3.9%) but statistically significant increase in peak oxygen uptake and a larger (13.2%) statistically significant increase in time to fatigue. The authors concluded that 7 days of quercetin could increase endurance and they suggested that this could be important for athletes and military personnel.

A subsequent 2012 study from the Military Performance Division, USARIEM, Natick, Massachusetts, evaluated the short-term effects of quercetin supplementation on soldier performance (15). This was a double-blind, placebo-controlled, crossover study. A total of 16 male soldiers took part in the study which was designed as follows.

The effects of three days of aerobically demanding exercise were evaluated at baseline, with quercetin supplementation or with placebo supplementation. On the plus side, there was a significant increase in quercetin levels after quercetin supplementation (1000mg/day for 8.5 days) but on the negative side, this increase in quercetin level did not translate into any improvement in performance.

The performance was assessed by measuring exercise time, oxygen peak, respiratory exchange ratios or levels of perceived exertion.

This next study is of relevance to both endurance and immunity/inflammation (16). A total of 20 endurance athletes took either Q chew (quercetin 1000mg, epigallocatechin 120 mg, isoquercetin 400mg, eicosapentaenoic acid 400mg, docosahexaenoic acid 400mg, vitamin C 1000mg and niacinamide 40mg) or placebo chews 15 minutes before a two-hour run.

Exercise was noted to significantly increase CRP and inflammatory cytokines. Significant increases in plasma quercetin levels were noted followed ingestion of Q chews but no changes in white blood cells, CRP,  inflammatory cytokines or oxidative burst activity was noted.

A suite of studies evaluated the effects of quercetin in 63 ultramarathon runners competing in the 160-km Western States Endurance Run.

In the first study which took place in 2007, quercetin ingestion at a dose of 1000mg per day taken for 21 days prior to the run did increase quercetin levels but did not affect muscle damage, inflammation, plasma cytokine or hormone levels (17).

In a follow-up study in 2009, the same group of researchers found that 21 days of 1000mg of quercetin supplementation versus placebo in 63 ultramarathon runners did not affect race time or rates of perceived exertion (18). Significant differences were noted in both serum glucose and cortisol throughout the race between the treatment and placebo arm of the study.

Bottom Line

The science is conflicting on quercetin as ergogenic. Looking very simply at the results we have, quercetin helped with physical performance in untrained but not trained men.

Does It Fight Cancer?

Flavonoid-rich diets have been shown to reduce the risks of certain cancers (19). As an example, a study in 27,111 healthy male smokers (50-69 years) showed that a flavonoid-rich diet may decrease pancreatic cancer risk in male smokers who so not consume supplemental alpha-tocopherol and/or beta-carotene.

But what about our favorite flavonoid, quercetin?

Quercetin has been shown to inhibit mTOR signaling which makes it interesting as a potential anticancer agent (20). mTOR stands for mammalian target of rapamycin and plays a central role as a regulator of cell metabolism, growth, proliferation, and survival.

A study in healthy volunteers showed that quercetin has effects on matrix metalloproteinase gene regulation which again is a potential mechanism by which quercetin could have anti-tumor effects (21).

An Iranian literature review of curcumin, quercetin, and allicin concluded that all three foods ‘seemed’ to be good candidates for management of gastric cancer through their pro-apoptotic, antiproliferative, and anti-helicobacter activities. (22).

A systematic review of the literature from Iran evaluated the utility of quercetin in ovarian cancer(23).

They found 220 relevant papers but only 13 publications were suitable for inclusion on the meta-analysis including 1 prospective, 2 case-control, 1 animal, and 9 in vitro human and animal cancer cell lines studies were eligible. They concluded that while the in vitro and animal studies were promising as they showed anticancer effects via inhibiting tumor growth, and angiogenesis, interrupt the cell cycle, and induce apoptosis.

However epidemiological studies did not confirm the  potentially protective effects of quercetin in ovarian cancer risk at levels commonly consumed (1.01-31.7 mg/day) in a typical diet

There is also interest in the possible role of quercetin as an anti-melanoma agent in refractory cases but this is all very theoretical at this stage (24).

 Bottom Line

There is no information on a clinical role for quercetin as an anti-cancer agent.

Is It Good For The Skin?

Theoretically, quercetin should not be bad for your skin, considering the fact that it is a flavonol. That is a far cry from being proven as a credible remedy for specific skin conditions or indications.

There are a number of studies for the search term ‘quercetin and skin’. Alas, and alack, most of these are all about the quercetin content of onion ‘skin’.

The only human clinical trial relevant to this subject is a study looking at using lipid nanoparticles to improve the delivery of quercetin to the skin (25).

Bottom Line

There is no evidence to support the use of quercetin in skin health.

Other Possible Uses of Quercetin?

Researchers from North Carolina carried out a large based community study in  941 people who received either 500 mg/day or 1000 mg/day quercetin, or placebo for 12-weeks (26). Quercetin supplementation quercetin did not have beneficial effects on memory, psychomotor speed, reaction time, attention, or cognitive flexibility. Again this negative result was seen despite large increases in plasma quercetin levels among the quercetin treatment groups.

The authors concluded that the ‘study raises concerns regarding the generalizability of positive findings of in vitro and animal quercetin research, and provides evidence that quercetin may not have an ergogenic effect on neurocognitive functioning in humans’.

Topical quercetin may help in the healing of aphthous mouth ulcers based on data from 40 male study subjects (27).

Quercetin has also been shown to alleviate the symptoms of interstitial cystitis in 22 men in a 4-week open-label trial (28).

A Special Mention For Isoquercetin

We have seen that quercetin, as found in nature, is a complex compound. Isoquercetin is an enzymatically modified form of quercetin. It is found in nature in rhubarb. A study in 20 subjects with allergic Japanese pollinosis compared isoquercetin with placebo for 8 weeks of the allergy season. They found a statistically significant reduction in the score for eye itch but a non-significant effect on nasal obstruction, watering eyes or activities 0f daily living (29).

 Is Quercetin Safe?

A review of the safety of quercetin was just published this year (30). The authors point of that the doses of quercetin sold as supplements far exceeds the usual dietary intake (1000mg per day versus 50 mg per day). Following their own review of published data, they conclude that quercetin is generally safe when taken at doses of up to 1000 mg per day for up to 12 weeks but that there is no information on higher doses for longer periods of time.

They caution against three possible adverse reactions:

  • renal damage in patients with pre-existing renal disease
  • promotion or worsening of cancers that are estrogen-dependent e.g. some form of breast or ovarian cancer
  • interactions between quercetin and other medications.

To understand the issue of drug-drug interactions more, let’s look at a classical pharmacokinetic study which looked at the interaction between quercetin and midazolam (a sedative we use in hospitals when people are having minor procedures) (31).

The study showed that repeated quercetin intake can reduce systemic exposure to the orally given drug by increasing its CYP3A-catalyzed metabolism. This means that some drugs for epilepsy, HIV infection, BP may have reduced efficacy if people take daily quercetin.

Conclusion

I have a strong suspicion that Mother Nature watches humankind and laughs at our inept attempts to outsmart her. The quercetin show is likely one of her favorite sitcoms. (I bet her favorite episode is the one with quercetin in Tang orange). We are a funny bunch indeed. We try to reduce an incredibly complex biochemical and physiological process to a single compound in a jar (ideally delivered by Amazon Prime).

We have seen that quercetin behaves differently when in its natural form and released by chewing as opposed to in a jar. We have seen that quercetin behaves differently in different populations (trained versus untrained). We have seen that it is not just quercetin but the quercetin family.

My bottom line here is that we probably only understand a fraction of the science behind quercetin.

Given our lack of knowledge, I think that there is theoretical and biological evidence that quercetin (as found in nature) is probably health promoting. I don’t think we can say much more than that. I think that trying to reduce quercetin to a simple biochemical compound for a single health benefit (or handy-dandy infographic) is missing the point entirely.

Remember the childhood cartoon Popeye? He used spinach as an ergogenic. Spinach, not quercetin pills.

My advice is to ensure an adequate natural supply of quercetin in your diet.