July 2018 Issue

Quercetin in the Spotlight
By Densie Webb, PhD, RD
Today's Dietitian
Vol. 20, No. 7, P. 22

The revered flavonoid receives much attention, but are there still more questions than answers about its health effects?

Quercetin, a member of the flavonoid family present in commonly consumed foods, has drawn attention in nutrition circles for its potential to affect a wide range of biological actions, including anticarcinogenic, anti-inflammatory, and antiviral activities, as well as for its ability to reduce lipid peroxidation and platelet aggregation, which, if unchecked, can lead to blood clots.1

Quercetin represents the majority of flavonoid intake in the diet and is one of the most studied for its potential health benefits. Because quercetin has been shown to scavenge free radicals, researchers have suggested that it may aid in the prevention of diseases such as cancer and atherosclerosis and reduce chronic inflammation, which is implicated as the root cause for a host of diseases and conditions.2,3

Flavonoids in Food
Considered to be natural antioxidants, flavonoids are commonly found in plant-based foods, including red wine, grapefruit, onions, apples, black tea, leafy green vegetables, broccoli, beans, cranberries, dark cherries, buckwheat, nuts, and, perhaps surprisingly, capers, which are one of the richest sources.1

The daily intake of quercetin in a typical Western diet is estimated to range between 0 and 30 mg, with a median of 10 mg.4 It would take approximately 100 g (3.5 oz) of fresh red onion to be comparable to 500 mg of quercetin supplements in tablet form.5

Food preparation and storage can affect quercetin concentrations. For example, foods that have been fried and boiled have lower quercetin levels. Boiling causes the greatest decrease by degrading the quercetin, which leaches out into the boiling water.6 The degree of quercetin loss varies among foods; onions, for example, can be stable up to temperatures of 212° F (boiling).

Quercetin content also depends on how food is stored. Onions can lose 25% to 33% of their quercetin content in the first 12 days of storage, but suffer minimal losses after that.7 In contrast, the quercetin level in strawberries has been shown to increase approximately 32% when stored at -4° F for nine months.

How and where foods are grown also affects quercetin content. For example, flavonol content is greater in plants exposed to higher levels of ultraviolet-B rays, possibly the result of a defense mechanism against UV light. Plants grown in the United Kingdom (UK) were found to have lower flavonol levels than those grown in South Africa because of the UK's greater use of greenhouses, which block the ultraviolet-B rays.6

Quercetin Absorption
While laboratory findings confirm the powerful effects of quercetin, it's unknown how the flavonoid develops these attributes or whether they translate to benefits in humans. In fact, the antioxidant capability of flavonoids found in laboratory studies may be irrelevant because it's yet to be determined how well they're absorbed by the body.

Recent studies suggest that while most of quercetin is excreted in the urine, much of what's consumed is first absorbed from the intestine and converted to its metabolites.1 "It's very difficult to know how much of a bioactive compound like quercetin is getting absorbed in the small intestine, which tissues may be positively affected, and for how long," says Ginger Hultin, MS, RDN, CSO, a spokesperson for the Academy of Nutrition and Dietetics.

One study found that repeated intake of onion, a rich source of quercetin, results in the accumulation of quercetin metabolites in tissues and blood, indicating regular consumption is required to keep blood and tissue levels high. Also, quercetin's absorption appears to be enhanced when consumed with oil.8

The conversion of quercetin to its metabolites must be taken into account when assessing its bioavailability.1 The synthesis of quercetin metabolites appears to be key to understanding exactly how the flavonoid acts as an antioxidant. The metabolites may, in fact, work better together than as single compounds. Metabolites of quercetin have less free radical scavenging activity than quercetin itself, but some still demonstrate antioxidant activity.1

What Studies Show
Findings about quercetin's potential effects on health, while encouraging, have been inconsistent. "Right now," Hultin says, "there are no conclusive studies on any of these outcomes. Many studies are small, are done on animals, and have a wide variety of dosing or standardization."

Almost all of quercetin's potential benefits relate to its action as an anti-inflammatory compound. Researchers at the Linus Pauling Institute in Oregon found quercetin to be a powerful antioxidant in the test tube but were unable to establish any measurable benefits in human subjects. While studies have shown that populations with high intakes of flavonoids in general have lower risk of several diseases related to inflammation,9-11 quercetin doesn't exist in foods alone, making it almost impossible to separate its effects from other flavonoids.

Cancer
Epidemiologic studies have suggested that the consumption of flavonoids, including quercetin, is closely associated with a reduced cancer incidence.12-14 Potential anticancer effects of flavonoids, including quercetin, have been observed in the lab and in animal studies. For example, animal studies have found supplementation with quercetin to inhibit the growth of leukemia, and breast and liver cancer cells.15-17

However, it's difficult to assess quercetin's anticarcinogenic effect in the human body. Thus far, there's no evidence that quercetin alone has a specific anticancer effect in humans.

CVD
Research on quercetin supplements for cardiovascular conditions and CVD risk factors has yielded mixed results.

The Zutphen Elderly study in a Dutch population found that those who consumed diets high in flavonoids, including quercetin, had a lower incidence of coronary heart disease and stroke.18,19

Both population and clinical studies have provided some evidence that quercetin can reduce blood pressure. A recent meta-analysis of randomized controlled trials found a statistically significant effect of quercetin supplements on the reduction of blood pressure with doses of approximately 500 mg/day. It suggested that quercetin might be considered as an add-on to antihypertensive therapy. However, the researchers also stated that safety studies are needed because a 10- to 60-fold increase from the average dietary intake was required to see an effect.20

A recent review of several studies concluded that quercetin's antihypertensive action is likely the result of several factors, such as its effect on the elasticity of the vascular system, total blood volume, and the renin-angiotensin system.21

A 2011 Korean study of male smokers found that quercetin moderately reduced LDL cholesterol, raised HDL cholesterol, and lowered blood pressure and blood sugar slightly. Overall, human studies have found that oral intake of 150 to 730 mg/day for four to 10 weeks has antihypertensive effects in humans.21

However, these clinical studies featured quercetin supplements. It remains to be seen whether dietary quercetin, combined with other flavonoids in the diet, has more or less effect on cardiovascular risk factors, including blood pressure, compared with supplements.

Arthritis
Several animal studies have found quercetin supplementation to reduce the inflammation associated with rheumatoid arthritis and osteoarthritis.10,22,23 One recent randomized, double-blind, placebo-controlled clinical trial in which 50 women with rheumatoid arthritis were given 500 mg per day of quercetin or a placebo for eight weeks resulted in significant improvements in clinical symptoms of the disease.24

Prostatitis
While quercetin has been promoted as a potentially effective treatment for nonbacterial prostatitis, research is limited. A one-month, double-blinded, placebo-controlled trial of 30 men with prostatitis tested the potential effectiveness of supplemental quercetin (500 mg twice a day).25

Those who received quercetin experienced a statistically significant improvement in symptoms compared with placebo. However, little additional research has been conducted.

Athletic Performance
Quercetin also has been tested for its effect on exercise endurance. A randomized, double-blinded, placebo-controlled clinical trial was conducted with 26 badminton players for eight weeks. The subjects were randomly assigned to one of two groups to receive quercetin (1,000 mg) or placebo (1,000 mg dextrose). VO2 and time to exhaustion (TTE) was used for measuring performance. The researchers found a significant increase in TTE in the quercetin group, but no significant change in the placebo group.

In addition, an Italian study found that quercetin supplementation (totaling 1 g/d) before and after strenuous exercise enabled red blood cells to better cope with the oxidative insult that results from strenuous exercise.5 However, the supplement contained a far greater amount of quercetin than can be found in a typical diet.

Safety
With few or no reported toxicities in studies, dietary quercetin appears to be safe.8 Only a few studies have provided detailed information on adverse effects of quercetin supplements, especially for long-term treatment (more than 12 weeks) with high doses (1,000 mg/day or more).26 However, quercetin inhibits an important enzyme (CYP3A4) involved in the metabolism of many common medications; it can alter blood levels (either increase or decrease), and change the intended effect of the drugs.26

"Clients should speak with their doctor and pharmacist before taking quercetin if they're taking one of many common medications, including Celebrex, Dilantin, Coumadin, Elavil, Paxil, Prilosec, or Zoloft," Hutlin says.

The number of medications that may be affected—and to what extent—by taking quercetin supplements is unknown.

Based on animal studies in which quercetin was injected, the flavonoid may have a negative effect on kidney function, especially in those with kidney disease. However, there's limited research in humans in this area.26

In addition, a potential tumor-promoting effect has been found in animals given high doses of quercetin, primarily in estrogen-dependent cancers such as some breast cancers. This finding could be important for those who haven't yet been diagnosed. Although the studies were conducted under highly artificial circumstances, the authors of the safety review suggest the findings introduce the question of whether quercetin could promote the growth of estrogen-dependent tumors in humans. More research is needed, they say.

While studies in pregnant animals suggest that quercetin supplements have no ill effects, there's insufficient data from human studies to conclude they're safe for pregnant and breast-feeding women.26

Bottom Line
Limited research makes it difficult to ascertain whether the consumption of quercetin supplements is a case of "too much of a good thing makes a bad thing." It's unclear how "bioavailable" supplemental quercetin compares with quercetin obtained from fruits and vegetables.

In addition, it's unknown whether the flavonoid's beneficial effects are the result of the combination of phytochemicals naturally present in plant foods or if there could be adverse effects from consuming high doses of quercetin supplements, especially if taken over the long term.

In summary, the research suggests that while quercetin may hold great potential for reducing disease risk, it's too early to make recommendations for quercetin supplements. Counseling clients to consume several daily servings of fruits and vegetables rich in phytochemicals always is good advice. Combined with vitamins, minerals, and a collection of other phytochemicals, this eating pattern should provide a more than generous dose of quercetin.

— Densie Webb, PhD, RD, is a freelance writer, editor, and industry consultant based in Austin, Texas.

References
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