Understanding the Brain Health Benefits of Quercetin

September 24, 2023

Are you looking for a nutrient that could fight cognitive aging, COVID, and seasonal allergies?  Look no further, as quercetin may do all of these, given its wide range of health benefits.  Quercetin is a type of polyphenol called a flavonol, and it comes mainly from various fruits, vegetables, and tea.  Examples of foods where quercetin is richest are onions, capers, apple skin, leafy green vegetables, and herbs like oregano and dill.1  However according to US dietary guidelines, 50% of people don’t eat enough fruits, and a shocking 90% don’t eat enough leafy green veggies.2  On top of that, the amount of quercetin that we obtain from food can also vary significantly due to farming methods and quality of the soil, with up to a 10-fold difference in quercetin content being observed for the same vegetable in some studies.3  This is concerning, since quercetin provides many benefits due to its role in directly collecting and neutralizing harmful oxidative particles that can build up in the brain over time causing damaging inflammation.4  

Understanding How Quercetin Benefits Brain Health 

Several observational studies have reported a significant association between quercetin intake and reduced cognitive decline as well as risk of Alzheimer’s disease.5  In fact, a 2020 paper by Dr. Thomas Holland at Rush University Medical Center (and NeuroReserve medical advisor) reported a 48% reduced risk of Alzheimer’s disease in those consuming high amounts of flavonols.6  Other studies have found a reduction in beta amyloid concentration (the “plaques” associated with Alzheimer’s disease) in the brain  associated with greater quercetin consumption.7 

Here are specific ways in which quercetin supports brain health on a cellular level: 

  • Promoting neurogenesis involved in learning and memory:  Quercetin has been associated with improving memory and learning in several studies.  Also, evidence suggests that quercetin functions to prevent cell death in the hippocampus, a critical part of the brain involved in formation and conversion of memories from short- to long-term storage.4 
  • Lowering amount of amyloid beta (brain plaque) build up:  Quercetin helps reverse the toxic buildup of amyloid beta by binding to those molecules and preventing them from sticking together.  Quercetin has this important impact due to its unique structure, which allows it to bind to amyloid effectively.4 
  • Controlling neurotransmitter levels and neuroplasticity:  Quercetin has been shown to restore levels of critical neurotransmitters in models of Parkinson’s disease, as well as improve the plasticity of synapses in the brain, allowing neurons in the brain to rewire and form new connections.4,8  
  • Enhancing cerebral blood flow:  Quercetin has been shown to increase blood flow to the brain, enabling it to be properly nourished, which unsurprisingly has been linked to improved memory.4 
  • Reducing oxidative stress and inflammation due to antioxidant effects: Quercetin helps reduce damaging oxidative stress in many ways, particularly through activation of a biological pathway called Nrf2-ARE, which helps produce proteins involved in detoxification and elimination of harmful reactive oxygen species (ROS).9  These proteins work like little cleaners to get rid of ROS, which can damage your brain cells. 
  • Enhancing energy balance and metabolic regulation:  Quercetin increases the production of receptors that play an important role in regulating energy levels and metabolic rates.10  Given the importance of energy for the brain (our most energy-hungry organ!), these receptors are associated with reduced risk of Alzheimer’s and Parkinson’s disease.11 
  • Promoting mitochondrial production:  Quercetin has been associated with the production of mitochondria in the brain and muscles.12  Mitochondria are the energy factories in our cells, and producing new, healthy mitochondria is crucial for cells to survive and power a variety of functions. 

Quercetin and the ApoE4 Gene 

In addition to the previously mentioned brain benefits of quercetin, it may also be a particularly important nutrient for carriers of the ApoE4 gene.  As we mentioned in our previous article on ApoE4, this genetic variation significantly increases one’s risk for Alzheimer’s disease. 

Quercetin has been shown to decrease levels of inflammatory markers in ApoE4 research studies, and inhibit the formation of “inflammasomes,” bundles of proteins that trigger harmful inflammatory responses, leading to cell damage.13,14 

Quercetin also plays other roles in ApoE4 immune response.  One way that ApoE4 is believed to increase Alzheimer’s risk is by promoting disease-associated microglia (DAM), which is an altered state of the brain’s immune cells that is associated with neurodegeneration.  Evidence suggests that quercetin may prevent the activation of DAM in ApoE4 carriers.15  

Levels of the ApoE protein tend to be decreased in ApoE4 carriers, and quercetin supplementation has been shown to increase levels of ApoE, while also reducing buildup of amyloid beta plaques.16 

In a recently published research paper on precision nutrition for ApoE4 carriers, quercetin is specifically cited for its role in reducing inflammation and protecting the blood-brain barrier, both of which are detrimentally affected by ApoE4.  This paper also mentions that quercetin supplementation may be helpful to obtain the brain health benefits of quercetin (alongside quercetin from food) for ApoE4 carriers.15 

What Other Health Benefits Does Quercetin Provide? 

While there are many exciting brain benefits of quercetin, there are other noteworthy health benefits of quercetin as well. 

Allergies:  Quercetin can help with allergies, since it regulates immune responses to allergens.  For example, flavonols (quercetin’s family of nutrients) have been shown to inhibit the release of histamine, which causes many common allergy symptoms.  Quercetin also inhibits inflammatory molecules and cell types that contribute to an allergy response.17 

COVID:  You may have heard about quercetin during the COVID pandemic due to its potential role in preventing and treating COVID.  Research suggests that quercetin may help fight COVID by inhibiting and reducing the levels of the hACE-2 receptor, which is how the COVID virus enters human cells.  Additionally, quercetin helps inhibit the release of inflammatory substances associated with a COVID infection and reduces levels of proteins that the COVID virus needs to replicate.18 

In addition to helping with allergies and COVID, the overall anti-inflammatory properties of quercetin may offer many other potential benefits, especially related to chronic inflammation. 

Quercetin Synergizes with Other Nutrients to Amplify Benefits 

One of quercetin’s most powerful secrets is its cooperation with other nutrients! 

For instance, omega-3’s and quercetin work together to enhance neuroprotective effects, including decreasing oxidative stress and restoring neurotransmitters.19.20  Also, quercetin works with its fellow flavonols, kaempferol, and myricetin, producing further anti-inflammatory effects.21  

The combination of vitamin E with quercetin enhances the ability of quercetin to cross the blood-brain barrier and exert its neuroprotective effects in the brain.22  Resveratrol is another polyphenol which has potent anti-inflammatory properties and is involved in modulating immune responses in the brain, and when combined with quercetin, another potent polyphenol, these two nutrients often work synergistically to enhance their anti-inflammatory effects.23 

A nice summary of its other benefits can be found here. 

Dosage of Quercetin for a Healthy Brain and Lifelong Brain Health 

As you can see, there are many health benefits associated with quercetin, and it can be hard to know how much supplementation can be potentially helpful. Research suggest quercetin intake of 50-100 mg per day (and maybe more, depending on circumstances).  This is based upon the amounts of quercetin consumed in observational studies associated with the lowest risk of Alzheimer’s, as well as the amount of quercetin consumed in a brain-healthy diet such as the MIND/Mediterranean dietary patterns.24,25 

Regarding our product RELEVATE, it provides quercetin paired with flavonoids kaempferol and myricetin, along with two forms of vitamin E to increase the transport of quercetin into the brain, and omega-3's to maximize antioxidant effects.  Learn more about RELEVATE by visiting here.  

Quercetin may sound quirky, but it will make you quick in the brain!

References

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  1. Montgomery, D. R. & Biklé, A. Soil Health and Nutrient Density: Beyond Organic vs. Conventional Farming. Front. Sustain. Food Syst. 5, 1–14 (2021).
  2. Khan, H., Ullah, H., Aschner, M., Cheang, W. S. & Akkol, E. K. Neuroprotective effects of quercetin in alzheimer’s disease. Biomolecules 10, (2020).
  3. Nakagawa, T. et al. Improvement of memory recall by quercetin in rodent contextual fear conditioning and human early-stage Alzheimer’s disease patients. Neuroreport 27, (2016).
  4. Holland, T. M. et al. Dietary flavonols and risk of Alzheimer dementia. Neurology 94, e1749–e1756 (2020).
  5. Maria, S. A. et al. The flavonoid quercetin ameliorates Alzheimer’s disease pathology and protects cognitive and emotional function in aged triple transgenic Alzheimer’s disease model mice. Neuropharmacology 93, 134–145 (2015).
  6. Sharma, S., Raj, K. & Singh, S. Neuroprotective Effect of Quercetin in Combination with Piperine Against Rotenone- and Iron Supplement–Induced Parkinson’s Disease in Experimental Rats. Neurotox. Res. 37, 198–209 (2020).
  7. Costa, L. G., Garrick, J. M., Roquè, P. J. & Pellacani, C. Mechanisms of Neuroprotection by Quercetin: Counteracting Oxidative Stress and More. Oxid. Med. Cell. Longev. (2016). doi:10.1155/2016/2986796
  8. Lee, S. M., Moon, J., Cho, Y., Chung, J. H. & Shin, M. J. Quercetin up-regulates expressions of peroxisome proliferator-activated receptor γ, liver X receptor α, and ATP binding cassette transporter A1 genes and increases cholesterol efflux in human macrophage cell line. Nutr. Res. 33, 136–143 (2013).
  9. Tyagi, S., Gupta, P., Saini, A., Kaushal, C. & Sharma, S. The peroxisome proliferator-activated receptor: A family of nuclear receptors role in various diseases. J. Adv. Pharm. Technol. Res. 2, 236–240 (2011).
  10. Davis, J. M., Murphy, E. A., Carmichael, M. D. & Davis, B. Quercetin increases brain and muscle mitochondrial biogenesis and exercise tolerance. Am. J. Physiol. Integr. Comp. Physiol. 296, R1071–R1077 (2009).
  11. Domiciano, T. P. et al. Quercetin Inhibits Inflammasome Activation by Interfering with ASC Oligomerization and Prevents Interleukin-1 Mediated Mouse Vasculitis. Sci. Rep. 7, 1–11 (2017).
  12. Boesch-Saadatmandi, C., Wolffram, S., Minihane, A. M. & Rimbach, G. Effect of apoE genotype and dietary quercetin on blood lipids and TNF-α levels in apoE3 and apoE4 targeted gene replacement mice. Br. J. Nutr. 101, 1440–1443 (2009).
  13. Norwitz, N. G., Saif, N., Ariza, I. E. & Isaacson, R. S. Precision Nutrition for Alzheimer’s Prevention in ApoE4 Carriers. Nutrients 13, 1362 (2021).
  14. Zhang, X. et al. Quercetin stabilizes apolipoprotein e and reduces brain Aβ levels in amyloid model mice. Neuropharmacology 108, 179–192 (2016).
  15. Mlcek, J., Jurikova, T., Skrovankova, S. & Sochor, J. Quercetin and its anti-allergic immune response. Molecules 21, 1–15 (2016).
  16. Imran, M. et al. The Therapeutic and Prophylactic Potential of Quercetin against COVID-19: An Outlook on the Clinical Studies, Inventive Compositions, and Patent Literature. Antioxidants 11, (2022).
  17. Denny Joseph, K. M. & Muralidhara. Combined Oral Supplementation of Fish Oil and Quercetin Enhances Neuroprotection in a Chronic Rotenone Rat Model: Relevance to Parkinson’s Disease. Neurochem. Res. 40, 894–905 (2015).
  18. Denny Joseph, K. M. & Muralidhara. Enhanced neuroprotective effect of fish oil in combination with quercetin against 3‐nitropropionic acid induced oxidative stress in rat brain. Prog. Neuro-Psychopharmacology Biol. Psychiatry 40, 83–92 (2013).
  19. García-Mediavilla, V. et al. The anti-inflammatory flavones quercetin and kaempferol cause inhibition of inducible nitric oxide synthase, cyclooxygenase-2 and reactive C-protein, and down-regulation of the nuclear factor kappaB pathway in Chang Liver cells. Eur. J. Pharmacol. 557, 221–229 (2007).
  20. Ferri, P. et al. Enhancement of flavonoid ability to cross the blood-brain barrier of rats by co-administration with [small alpha]-tocopherol. Food Funct. 6, 394–400 (2015).
  21. Lu, X. et al. Resveratrol differentially modulates inflammatory responses of microglia and astrocytes. J. Neuroinflammation 7, 1–14 (2010).
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  23. Zamora-Ros, R. et al. Dietary Intakes of Individual Flavanols and Flavonols Are Inversely Associated with Incident Type 2 Diabetes in European Populations. J. Nutr. 144, 335–343 (2014).
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