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Quercetin: Scientific studies + genetic connections

Quercetin is a natural flavonoid acting as both an antioxidant and anti-inflammatory. This potent flavonoid is found in low levels in many fruits and vegetables, including elderberry, apples, and onions.

As a supplement, quercetin has many positive health benefits. This article focuses on the results of clinical trials involving quercetin as well as linking to specific genetic topics. By using your genetic data, you can make a more informed decision on whether quercetin is worth trying.

Quercetin Research:

Quercetin has been shown in cell studies to be a fabulous, wonder-supplement for many different conditions. You may have read about how great it is on Facebook or other websites.

But… the studies in humans don’t always match up with the cell studies and animal studies. I’m going to focus mainly on the results of human trials of quercetin and dive into cell studies just for the genetic links.

Food sources of quercetin:

Quercetin is a flavonol found at low levels in a lot of different fruits and vegetables. Here is a list of foods with a higher quercetin content (from Phenol-explorer and the USDA).

  • Capers: 234mg/100g
  • Black elderberry: 42 mg/100g
  • Dark chocolate: 25 mg/100g
  • Shallots and onions: 10 – 31mg/100g
  • Apples, with skin: 2 -4 mg/100g
  • Bilberry: 1.27/100g
  • Red Wine: 0.83 mg/100 ml
  • Apple juice: 0.48 mg/ 100ml

Blood pressure reduction studies that use quercetin:

In a double-blind, randomized placebo-controlled study, quercetin reduced blood pressure in men with hypertension. The study used 730 mg/day of quercetin and found that it reduced systolic blood pressure by 7 mmHg and diastolic blood pressure by 5 mmHg.[ref]

Another study using a smaller dosage of quercetin had a smaller decrease in blood pressure. The study results showed a decrease in systolic blood pressure of 3.6 mmHg in overweight patients with high blood pressure using only 162 mg/day of quercetin.[ref]

A meta-analysis that combined the data from 7 clinical trials found a significant reduction in blood pressure in randomized controlled trials that used doses of more than 500mg/day.[ref]

Quercetin for oxidative stress and oxidized LDL:

When a cell has an imbalance of reactive oxygen species (ROS) to antioxidants, it is called oxidative stress. These reactive oxygen species contain an unstable balance of electrons and can cause reactions that damage the cell. Too much oxidative stress can cause DNA damage, the production of inflammatory signals, and eventually cell death.

Quercetin is a free radical scavenger shown in studies to help prevent oxidized cholesterol.[ref] This is important because oxidized cholesterol may accelerate atherosclerosis or plaque build-up in the arteries.[ref]

A double-blinded, placebo-controlled cross-over trial in overweight adults with metabolic syndrome found that 150mg/day of quercetin decreased the concentration of oxidized LDL cholesterol. There wasn’t much of an effect on any other health markers at this dosage, but just decreasing the oxidized LDL should reduce the risk of cardiovascular disease.[ref]

Researchers theorize that oxidative stress contributes to Alzheimer’s disease pathology. Animal and cell studies show that quercetin can protect against oxidative stress in the brain and partially prevent the associated neuronal toxicity.[ref]

Related article: APOE and Alzheimer’s Risk

Most of the time, preventing oxidative stress is something you want to do – but not always. One of the benefits of exercise is to create stress, which causes cells to respond by adapting and producing more mitochondria. Quercetin’s effect on exercise performance has been researched. The results of the studies have varied, but most show that quercetin doesn’t increase exercise performance.[ref] If you are supplementing with quercetin, consider whether you should take it at a time that it won’t interfere with the benefits of exercise-induced stress.

Related article: Athletic Performance Genes

Quercetin as a senolytic (longevity benefits):

Cellular senescence occurs when a cell can no longer divide or function normally. Basically, the cell just sits there, giving off pro-inflammatory signals. Those inflammatory factors can then impact the surrounding cells. Kind of like a drug dealer moving into the neighborhood… bringing down the whole area.

The body can get rid of senescent cells pretty well – up to a point. But when too many senescent cells accumulate, things start going downhill. Recent research points to senescent cells actually causing a lot of the diseases of aging, rather than just being a symptom of aging.

Clearing out senescent cells could either delay or possibly reverse aging. That would be pretty cool…

Quercetin has been studied recently as a senolytic – a way of clearing out senescent cells. Animal and cell studies are promising.[ref][ref]

But what about human trials? When quercetin is combined with Dasatinib (a leukemia drug), it clearly reduces senescent cells.[ref][ref] This is an exciting field of study that shows a lot of promise for the future.

One more way that quercetin may improve atherosclerosis and oxidized LDL is by reducing senescent cells in the endothelium (lining of the arteries). A new study looked at quercetin’s effect on a cell model of atherosclerosis. The study found that quercetin inhibited the foam cells created by oxidized LDL in atherosclerosis, and it also decreased senescent cells. While just a cell study, this points to quercetin possibly having multiple beneficial effects on cardiovascular disease.[ref]

Related article: NAD+, nicotinamide riboside, and NMN

Advanced glycation end products:

The production of advanced glycation end products (AGEs) in the body (and through foods we eat) increases the diseases of aging. For AGEs that are produced in the body, methylglyoxal levels are important.

A randomized, double-blind, placebo-controlled crossover trial found that 160 mg/d of quercetin reduced methylglyoxal, a precursor for AGEs, by an average of 11% after four weeks.[ref]

Related article: Advanced Glycation End Products and your genes

Uric acid:

High uric acid levels are a risk factor for gout. A double-blind, placebo-controlled cross-over trial in healthy men with higher uric acid found that quercetin lowered uric acid levels. The trial used 500mg/day of quercetin for four weeks and decreased uric acid by 26·5 µmol/l  on average.[ref]

Related article: Gout genes

Rheumatoid Arthritis:

Since quercetin can reduce both pain and inflammation, it makes sense that it could help with rheumatoid arthritis. Indeed, a two-month placebo-controlled trial found that quercetin reduced morning pain, stiffness, and post-activity pain. Quercetin also reduced TNF-alpha (inflammatory cytokine) levels. The trial included 50 women with RA who took either 500mg/day of quercetin or a placebo.[ref]

Related article: TNF-alpha and rheumatoid arthritis

Immune boosting:

A randomized placebo-controlled trial found that 12 weeks of quercetin at 1000mg/day reduced upper respiratory tract infections.[ref]

Excessive exercise can make you more susceptible to getting sick. In a mouse trial where the mice exercised to fatigue (treadmill) for days, researchers found that quercetin offsets the increased propensity to get sick after exercising to fatigue.[ref] This may be something to try if you are training for an upcoming exercise-intensive event.

A human study showed that quercetin was safe (>5g/day) and effective for some people in reducing the viral load in hepatitis C patients.[ref]

Mast Cell Blocker:

Mast cells are an important part of the immune system that can degranulate and signal for an inflammatory response. Overactive mast cells can be a problem, leading to allergic responses or to mast cell activation syndrome. One compound that mast cells can release is histamine.

Quercetin stabilizes mast cells and inhibits the release of histamine.[ref]

Related article: Mast Cell Activation Syndrome Genes

Caffeine and quercetin (CYP1A2 gene):

Quercetin inhibits CYP1A2, which is the enzyme the body uses to metabolize caffeine.[ref] If you are a slow metabolizer of caffeine, quercetin along with caffeine, may mean that you feel the effects of caffeine for a longer period of time.

Related article: CYP1A2 Variants

Neuroprotective:

Coffee has often been linked in epidemiological studies to reduced risk of Parkinson’s and possibly Alzheimer’s. The reason, according to some researchers, is the quercetin that is found in low levels in coffee. [ref]


Absorption, bioavailability, transport, and metabolism of quercetin

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References

1 Edwards, Randi L., et al. “Quercetin Reduces Blood Pressure in Hypertensive Subjects.” The Journal of Nutrition, vol. 137, no. 11, Nov. 2007, pp. 2405–11. Silverchair, doi:10.1093/jn/137.11.2405.
2 Brüll, Verena, et al. “Effects of a Quercetin-Rich Onion Skin Extract on 24 h Ambulatory Blood and Endothelial Function in Overweight-to-Obese Patients with (Pre-)Hypertension: A Randomised Double-Blinded Placebo-Controlled Cross-over Trial.” The British Journal of Nutrition, vol. 114, no. 8, Oct. 2015, pp. 1263–77. PubMed Central, doi:10.1017/S0007114515002950.
3 Serban, Maria-Corina, et al. “Effects of Quercetin on Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.” Journal of the American Heart Association, vol. 5, no. 7, July 2016. PubMed, doi:10.1161/JAHA.115.002713.
4 D’Andrea, Gabriele. “Quercetin: A Flavonol with Multifaceted Therapeutic Applications?” Fitoterapia, vol. 106, Oct. 2015, pp. 256–71. ScienceDirect, doi:10.1016/j.fitote.2015.09.018.
5 Staprans, Ilona, et al. “The Role of Dietary Oxidized Cholesterol and Oxidized Fatty Acids in the Development of Atherosclerosis.” Molecular Nutrition & Food Research, vol. 49, no. 11, Nov. 2005, pp. 1075–82. PubMed, doi:10.1002/mnfr.200500063.
6 Egert, Sarah, et al. “Quercetin Reduces Systolic Blood Pressure and Plasma Oxidised Low-Density Lipoprotein Concentrations in Overweight Subjects with a High-Cardiovascular Disease Risk Phenotype: A Double-Blinded, Placebo-Controlled Cross-over Study.” The British Journal of Nutrition, vol. 102, no. 7, Oct. 2009, pp. 1065–74. PubMed, doi:10.1017/S0007114509359127.
7 Godoy, Juan A., et al. “Quercetin Exerts Differential Neuroprotective Effects Against H2O2 and Aβ Aggregates in Hippocampal Neurons: The Role of Mitochondria.” Molecular Neurobiology, vol. 54, no. 9, 2017, pp. 7116–28. PubMed, doi:10.1007/s12035-016-0203-x.
8 Askari, Gholamreza, et al. “Does Quercetin and Vitamin C Improve Exercise Performance, Muscle Damage, and Body Composition in Male Athletes?” Journal of Research in Medical Sciences : The Official Journal of Isfahan University of Medical Sciences, vol. 17, no. 4, Apr. 2012, pp. 328–31.
9 Kim, Seo Rin, et al. “Increased Renal Cellular Senescence in Murine High-Fat Diet: Effect of the Senolytic Drug Quercetin.” Translational Research: The Journal of Laboratory and Clinical Medicine, vol. 213, 2019, pp. 112–23. PubMed, doi:10.1016/j.trsl.2019.07.005.
10 Ogrodnik, Mikolaj, et al. “Obesity-Induced Cellular Senescence Drives Anxiety and Impairs Neurogenesis.” Cell Metabolism, vol. 29, no. 5, May 2019, pp. 1061-1077.e8. PubMed Central, doi:10.1016/j.cmet.2018.12.008.
11 Hickson, LaTonya J., et al. “Senolytics Decrease Senescent Cells in Humans: Preliminary Report from a Clinical Trial of Dasatinib plus Quercetin in Individuals with Diabetic Kidney Disease.” EBioMedicine, vol. 47, Sept. 2019, pp. 446–56. PubMed, doi:10.1016/j.ebiom.2019.08.069.
12 Kim, Eok-Cheon, and Jae-Ryong Kim. “Senotherapeutics: Emerging Strategy for Healthy Aging and Age-Related Disease.” BMB Reports, vol. 52, no. 1, Jan. 2019, pp. 47–55. PubMed Central, doi:10.5483/BMBRep.2019.52.1.293.
13 Cao, Hui, et al. “Quercetin Suppresses the Progression of Atherosclerosis by Regulating MST1-Mediated Autophagy in Ox-LDL-Induced RAW264.7 Macrophage Foam Cells.” International Journal of Molecular Sciences, vol. 20, no. 23, Dec. 2019. PubMed, doi:10.3390/ijms20236093.
14 Van den Eynde, Mathias D. G., et al. “Quercetin, but Not Epicatechin, Decreases Plasma Concentrations of Methylglyoxal in Adults in a Randomized, Double-Blind, Placebo-Controlled, Crossover Trial with Pure Flavonoids.” The Journal of Nutrition, vol. 148, no. 12, Dec. 2018, pp. 1911–16. Silverchair, doi:10.1093/jn/nxy236.
15 Shi, Yuanlu, and Gary Williamson. “Quercetin Lowers Plasma Uric Acid in Pre-Hyperuricaemic Males: A Randomised, Double-Blinded, Placebo-Controlled, Cross-over Trial.” The British Journal of Nutrition, vol. 115, no. 5, Mar. 2016, pp. 800–06. PubMed, doi:10.1017/S0007114515005310.
16 Javadi, Fatemeh, et al. “The Effect of Quercetin on Inflammatory Factors and Clinical Symptoms in Women with Rheumatoid Arthritis: A Double-Blind, Randomized Controlled Trial.” Journal of the American College of Nutrition, vol. 36, no. 1, 2017, pp. 9–15. PubMed, doi:10.1080/07315724.2016.1140093.
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18 Davis, J. M., et al. “Quercetin Reduces Susceptibility to Influenza Infection Following Stressful Exercise.” American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, vol. 295, no. 2, Aug. 2008, pp. R505-509. PubMed, doi:10.1152/ajpregu.90319.2008.
19 Lu, Nu T., et al. “A Phase I Dose Escalation Study Demonstrates Quercetin Safety and Explores Potential for Bioflavonoid Antivirals in Patients with Chronic Hepatitis C.” Phytotherapy Research : PTR, vol. 30, no. 1, Jan. 2016, pp. 160–68. PubMed Central, doi:10.1002/ptr.5518.
20 Weng, Zuyi, et al. “Quercetin Is More Effective than Cromolyn in Blocking Human Mast Cell Cytokine Release and Inhibits Contact Dermatitis and Photosensitivity in Humans.” PLoS ONE, vol. 7, no. 3, Mar. 2012. PubMed Central, doi:10.1371/journal.pone.0033805.
21 Xiao, Jian, et al. “Quercetin Significantly Inhibits the Metabolism of Caffeine, a Substrate of Cytochrome P450 1A2 Unrelated to CYP1A2*1C (-2964G>A) and *1F (734C>A) Gene Polymorphisms.” BioMed Research International, vol. 2014, 2014, p. 405071. PubMed, doi:10.1155/2014/405071.
22 Guo, Yi, et al. “Dietary Fat Increases Quercetin Bioavailability in Overweight Adults.” Molecular Nutrition & Food Research, vol. 57, no. 5, May 2013, pp. 896–905. PubMed, doi:10.1002/mnfr.201200619.
23 Čižinauskas, Vytis, et al. “Skin Penetration Enhancement by Natural Oils for Dihydroquercetin Delivery.” Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry, vol. 22, no. 9, Sept. 2017. PubMed Central, doi:10.3390/molecules22091536.
24 Han, S. B., et al. “Physical Characterization and in Vitro Skin Permeation of Solid Lipid Nanoparticles for Transdermal Delivery of Quercetin.” International Journal of Cosmetic Science, vol. 36, no. 6, Dec. 2014, pp. 588–97. PubMed, doi:10.1111/ics.12160.
25 Lee, Jung Eun, et al. “Quercetin Intake, MATE1 Polymorphism, and Metabolic Syndrome in Korean Population: Hallym Aging Study.” Food Science and Biotechnology, vol. 25, no. 6, Dec. 2016, pp. 1783–88. PubMed Central, doi:10.1007/s10068-016-0271-8.
26 Brüll, Verena, et al. “No Effects of Quercetin from Onion Skin Extract on Serum Leptin and Adiponectin Concentrations in Overweight-to-Obese Patients with (Pre-)Hypertension: A Randomized Double-Blinded, Placebo-Controlled Crossover Trial.” European Journal of Nutrition, vol. 56, no. 7, Oct. 2017, pp. 2265–75. PubMed, doi:10.1007/s00394-016-1267-0.
27 Heinz, Serena A., et al. “A 12-Week Supplementation with Quercetin Does Not Affect Natural Killer Cell Activity, Granulocyte Oxidative Burst Activity or Granulocyte Phagocytosis in Female Human Subjects.” The British Journal of Nutrition, vol. 104, no. 6, Sept. 2010, pp. 849–57. PubMed, doi:10.1017/S000711451000156X.


About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering from Colorado School of Mines and an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.