Any Merit to Quercetin's Anticancer Claims?

Darren J. Hein, PharmD

Disclosures

October 22, 2020

As a pharmacist, nearly a quarter of the questions I field from other pharmacists and healthcare providers are about dietary supplements. Once a supplement has gained mainstream attention, whether it be through headlines or social media posts, there's a good chance that it's being hyped as "the latest, greatest, all-natural cure," which unsurprisingly invites much curiosity. Such is the case with the interest surrounding the use of quercetin in preventing cancer.

Quercetin's antioxidant and anti-inflammatory effects have made it an increasingly popular supplement among those looking to boost immune, cardiovascular, and metabolic health. Over the past two decades, several preclinical reports on the antineoplastic effects of quercetin have been published. As with most unregulated and largely untested dietary supplements, though, quercetin's proposed health benefits are not built upon a foundation of high-quality evidence, but its popularity makes it worth exploring.

Quercetin is a plant flavonol from the flavonoid group of polyphenols. Found in many foods and teas, the highest concentrations are in capers, cilantro, red onion, kale, broccoli, apples, and certain berries (eg, chokeberry, cranberry, lingonberry). It is one of the most common flavonoids in the diet, with US adults estimated to consume around 12 mg of quercetin in their diet every day. It can also be purchased over the counter in supplements with doses ranging from 250 to 500 mg per capsule.


 

Naturally occurring quercetin differs from its commercially available supplement counterpart. This is a notable distinction, given that most research to date has focused on the dietary intake of quercetin. A handful of small, preliminary studies on the use of quercetin supplements for various health conditions have been published, but no high-quality clinical trials are available.

Dozens of animal and in vitro studies suggest that quercetin promotes apoptosis, stimulates autophagy, and induces cell-cycle arrest at various phases in cancer cells. These studies also show that quercetin can inhibit tumor angiogenesis and metastasis by targeting the vascular endothelial growth factor receptor 2–dependent pathway and inhibiting the epithelial-to-mesenchymal transition process, among other mechanisms.

But do these preclinical results translate to anticancer effects in humans?

Unfortunately, clinical trials addressing this question are lacking. Several observational studies evaluating the link between dietary flavonoid intake and cancer have been published, with many showing an inverse association. The best evidence looking specifically at quercetin intake comes from a 2013 pooled analysis of cohort and case-control studies by Woo and Kim. These researchers found that a higher intake of quercetin was associated with 20% lower odds of cancer, with an even greater risk reduction in smokers. However, individual studies addressing various forms of cancer show mixed results. For instance, an inverse association between quercetin intake and both pancreatic cancer and gastric cancer has been reported, whereas studies on bladder cancer and ovarian cancer risk failed to identify such a link. Observational research on quercetin's effect on lung cancer risk has been particularly conflicting, with separate studies showing no association, a trend toward inverse association, and a 35% lower odds of lung cancer with increased quercetin intake.

We must recognize that such studies cannot address causation, only association, making it difficult to say whether quercetin intake alone was responsible for the reduced cancer risk. Although most of the studies were adjusted to account for potential confounders, including intake of other flavonoids, use of other supplements, physical activity, education, and socioeconomic status, it's impossible to fully account for the known and unknown variables that might influence the results. To gather data for these studies, researchers must also rely on food diaries or the long-term memory of study participants' dietary habits, raising obvious concerns about reliability and recall bias.

Because these studies solely analyzed the dietary intake of quercetin, they tell us nothing about its possible effects when taken in supplement form. And although no safety concerns exist with quercetin from dietary sources, the long-term safety of supplemental quercetin is not well established in humans. Even if quercetin does have anticancer potential, its poor oral bioavailability may make these effects moot, although delivery systems to enhance absorption of quercetin are being investigated.

When discussing the proposed anticancer effects of quercetin, we must also be vigilant in calling out other preclinical research highlighting the possibility for quercetin-related drug interactions. Quercetin has been shown to interfere with several cytochrome P450 (CYP) isoenzymes and drug transporters, including inhibition of CYP2C9, CYP2D6, CYP3A4, organic anion transporting polypeptides, and P-glycoprotein. This suggests that quercetin may alter systemic exposure to a majority of prescription and nonprescription drugs on the market, including anticancer drugs.

Even if the jury is still out on quercetin's anticancer effects, and relevant concerns exist about its bioavailability, safety, and potential drug interactions, the evidence that suggests a lower risk for cancer with dietary intake could potentially be beneficial. While patients may wish to adopt healthier diets with foods known to contain high concentrations of quercetin and other flavonoids, it's too early for healthcare providers to specifically recommend quercetin, particularly in supplement form, for the prevention or treatment of cancer.

Darren Hein, PharmD, is an associate professor of pharmacy practice at Creighton University's School of Pharmacy and Health Professions in Omaha, Nebraska. Within the school, he serves as director of the Center for Drug Information & Evidence-Based Practice. Beyond teaching the principles of evidence-based practice, he lectures on dietary supplements within the pharmacy curriculum, serves as a peer reviewer for several complementary and alternative medicine–related journals, and is a contributor to Natural Medicines (formerly Natural Medicines Comprehensive Database).

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