How to Eat Your Hat

Quercetin works as a molecular helmet, protecting the brain from damage to its hard-working cells.

By Kirsi Goldynia, published November 6, 2018 - last reviewed on January 1, 2019

As diet moves beyond nutrition to playing a biologically active role in preventing disease, a number of substances found in everyday edibles have emerged as serious contributors to healthy minds and bodies. Curcumin, found in turmeric, has made the orange root famous for combating inflammation. Proanthocyanidins, which color cranberries, support urinary health. Omega-3 fats, in seaweed and salmon, foster development of the nervous system.

And then there's quercetin—a molecule found in red wine, onions, and a slew of foods in between that could satisfy even the pickiest bon vivant. It has neuroprotective properties that, scientists find, can  counter some of our most devastating disorders.

"Quercetin is a very powerful antioxidant," says Federico Dajas-Bailador, a professor of medicine at the University of Nottingham in the U.K. And the brain is a powerful generator of rogue oxygen molecules, a furnace of metabolic activity that burns glucose to power every move and meditation and then emits spent oxygen that is toxic to cells. Although it is plastic and resilient, the nervous system is nevertheless vulnerable to the maladies of such degradation—Alzheimer's disease among them—to say nothing of blunt force.

Multiple mechanisms have been put forth to explain quercetin's neuroprotective qualities. Although they have a number of nuanced differences, all function by targeting the same underlying problem: oxidative stress, an imbalance between the reactive oxygen species (ROS) generated and the antioxidant molecules available to keep them in check. Disease or trauma can spark an excess of ROS, and when they reach critical mass they subvert normal brain function.

"By acting as a scavenger of ROS, it has been hypothesized that quercetin regulates the molecules directly," says Dajas-Bailador. "But this is only one aspect of its antioxidant profile."

Quercetin also acts as a moderator of molecular pathways that lead to the production of other antioxidant enzymes and induce autophagy, a critical cellular upkeep process whereby damaged components are removed, restored, and recycled. Autophagy is especially critical in the metabolically active brain.

In disorders such as Alzheimer's disease or following a blow to the head, there's damage to the brain's mitochondria, the structures within cells that produce their operating power. When mitochondrial function goes awry, excess ROS is generated, creating oxidative stress. Coupled with the disruption of protein and DNA function, the upshot is brain cell death and loss of cognitive ability. Quercetin acts as a molecular helmet, ameliorating the oxidative stress and restoring mitochondrial function.  

Whether oxidative stress is a cause of Alzheimer's disease or secondary to other events, toxic amyloid beta protens build up in brain cells, killing them; oxidative stress exacerbates the pathologic process. Animal studies show that quercetin reduces both amyloid accumulation and cognitive and emotional symptoms.

"Quercetin has been observed to be highly protective to neurons against amyloid beta-associated oxidative stress," says University of Kentucky neurochemist D. Allan Butterfield, who has conducted in vitro studies of the agent. "Yet, one of the biggest questions is: What is the precise mechanism by which protective effects arise in vivo, in the brain?" Some studies suggest that quercetin upregulates the activity of a signaling pathway regulated by the protein sirtuin, inducing autophagy and ridding the brain of cellular debris.

Perhaps more intriguing, preliminary studies suggest that quercetin may boost the effectiveness of antipsychotic treatment in schizophrenia patients. It is thought that oxidative stress plays a role in the development of the disorder.

But quercetin is no cure-all. In high doses, Butterfield observes, it turns out to be toxic to neurons.

Daja-Bailador counts himself among the many who are sparking demand for foods and supplements that contain the brain-bolstering molecule. "I drink a strong tea of the Achyrocline satureioides plant [rich in free quercetin] every day."

A Spectrum of Activity
 

  • Quercetin is found in cranberries, cherries, apple peel, onions, black tea, cocoa powder, red wine, and buckwheat.
  • Quercetin is a flavonoid, a class of molecules that give plants their color.
  • Along with other flavonoids, quercetin is known as vitamin P for its ability to alter the permeability of blood vessels.
  • Quercetin is widely available as a supplement in pill, powder, and liquid formulations.
  • Quercetin is also sold as an anti-itch supplement for dogs.
  • The anti-inflammatory and immune-boosting effects of quercetin may have benefits in the treatment of chronic diseases.
  • Quercetin is also thought to reduce the risk of stroke, lower blood pressure, and inhibit cancer cell proliferation.
  • By inhibiting histamine, quercetin may provide allergy relief.
  • Hyperthermia, hypotension, and myocardial inflammation can often occur after heat stroke. Research suggests that quercetin may protect against these adverse effects.
  • For those athletically inclined, quercetin could provide a boost. A study found that it enhances the performance of cyclists.
  • At high doses, quercetin can damage the kidneys.

A Cell Saver

Quercetin

This antioxidant activity scavenges reactive oxygen species (ROS) and results in the reduction of oxidative stress as it:

  • Activates transcription factor Nrf2
  • Regulates expression of hundreds of genes
  • Increases antioxidant defense
  • Increases activity of Sirtuin 1 pathway
  • Increases transcription factor p53 activity
  • Increases antioxidant activity and autophagy