The Science Behind Quercetin
Quercetin
Did you know what is the connection between oak trees and our health? Yes, oxygen is a good answer but not the only one. Quercetin is another one. The word quercetin comes from the Latin word Quercus, which is a type of oak tree.
Quercetin is also called “the queen of flavonoids”, as it is one of the best-studied flavonoids. According to the USDA Database we can find it in fruit (especially berries), vegetables (like kale and onions), herbs (like dill and cilantro), seeds (like buckwheat) and tea (1). Everyone’s intake of quercetin depends a lot on their diet, with an average intake being between 20mg/day to more than 50mg/day (2).
Wondering what is all this fuss with quercetin? Well, hundreds of scientific studies report its potential health benefits, so, let’s take a closer look!
A senescent cell scavenger
Senescent cells are cells that have stopped proliferating either because they are old or because they are damaged. Today, senescent cells are viewed as a hallmark of aging because they can inhibit the proper function of the surrounding tissue. Some recent studies in cells (in vitro studies) and animals (in vivo studies) suggest that quercetin assists in eradicating these senescent cells (3-5). Removal of these cells can rejuvenate the tissues and, therefore, contribute to longevity. This is an exciting prospect to be validated in humans.
Fighting allergies and auto-immune diseases
Allergic reactions and autoimmune diseases, similar to persistent inflammation, take place when the immune system is overly active. So, it is not surprising that the immunomodulatory properties of quercetin come in handy for these conditions, too.
Quercetin has shown promise in many mouse models of auto-immune diseases including rheumatoid arthritis, multiple sclerosis, lupus erythematosus and atopic dermatitis (13). By stabilizing the immune system, it ameliorated the symptoms of the disease. Furthermore, in a clinical study of rheumatoid arthritis it reduced the pain and stiffness of patients and improved their overall quality of life (14).
In vitro and in vivo studies also show the potential of quercetin for allergic diseases, especially allergic asthma and allergic rhinitis (15). Quercetin interacts with mast cells and inhibits the release of histamine, which is the main driver of allergic symptoms.
An essential anti-oxidant
Oxidative stress can cause a great deal of damage to the whole body, therefore, it is a major factor in aging and a plethora of diseases (6). Oxidative stress takes place when there is an imbalance of oxidative molecules (free radicals like ROS – reactive oxygen species) and anti-oxidative mechanisms. Quercetin, like all flavonoids, is an antioxidant and helps keep this balance on the good side. How? In more than one way. To begin with, it directly scavenges free radicals (7). On top of that, it enhances the cell’s own antioxidant mechanisms, for example, the activity of antioxidant enzymes (8).
Given the damage oxidative stress is responsible for, these antioxidant properties are linked to multiple health benefits, some of which we see next.
A natural anti-hypertensive
Quercetin has powerful anti-hypertensive properties. Clinical trials showed that taking quercetin (more than 500mg/day) significantly lowered blood pressure after 8 weeks (16).
The action of quercetin on the cardiovascular system is twofold. First, it protects the blood vessels from oxidative stress and inflammation. As a result, the blood vessels are in “good shape” and resistant to hypertension (17). At the same time, quercetin, like other polyphenols, can directly regulate the transport of Na+ and Cl– in and out of the cells (18). Reducing the concentration of these ions in the blood, it lowers the blood pressure.
Fighting inflammation
Quercetin is a valuable partner when it comes to fighting inflammation. An abundance of in vitro and in vivo studies support this (9). Quercetin communicates with the immune cells (T-cells, microglial and mast cells) and “keeps them in check”. To achieve this, it inhibits pro-inflammatory enzymes and cytokines (molecules-messenger of the immune system) (10).
This interaction with the immune system needs further support from clinical trials. Nevertheless, quercetin, in combination with vitamin C, alleviated the symptoms and duration of respiratory infections (11). Also, it reduced the incidence of respiratory infection in athletes after intensive exercise (12).
An ally against cancer
Remember the free radicals we mentioned earlier? Free radicals can react with the DNA and as a result cause mutations. Accumulation of dangerous mutations in a cell can make it cancerous. By reducing the free radicals, antioxidants like quercetin help prevent cancer (19).
But it seems like the power of quercetin goes beyond that. Quercetin was toxic for cancer cells in culture and mice. It was able to impede specific types of cancer cells from surviving and growing. The best part? Because it targeted pathways specific to cancer growth that toxicity was very low for healthy cells (20).
Lastly, thanks to its antioxidant properties, quercetin when can help mitigate the toxicity of chemotherapy to healthy cells (21). These results come from cells in the lab and it would be interesting to see the effect in humans.
Conclusion
Quercetin is a powerful flavonoid with impressive health benefits. Some of these benefits like the antioxidant, immune-modulating and hypertensive properties are supported by clinical trials. For some others, primary results from cell and animal studies have already opened the way for further research.
References
1. Bhagwat, S., Haytowitz, D. B. & Holden, J. M. USDA Database for the Flavonoid Content of Selected Foods Release 3 Prepared by USDA Database for the Flavonoid Content of Selected Foods Release 3 Prepared by. U.S. Dep. Argiculture 1–156 (2011).
2. Ock, K. C., Sang, J. C. & Song, W. O. Estimated Dietary Flavonoid Intake and Major Food Sources of U.S. Adults. J. Nutr. 137, 1244–1252 (2007).
3. Shao, Z. et al. Senolytic agent Quercetin ameliorates intervertebral disc degeneration via the Nrf2/NF-κB axis. Osteoarthr. Cartil. 29, 413–422 (2021).
4. Saccon, T. D. et al. Senolytic Combination of Dasatinib and Quercetin Alleviates Intestinal Senescence and Inflammation and Modulates the Gut Microbiome in Aged Mice. J. Gerontol. A. Biol. Sci. Med. Sci. 76, 1895–1905 (2021).
5. Zoico, E. et al. Senolytic effects of quercetin in an in vitro model of pre-adipocytes and adipocytes induced senescence. Sci. Rep. 11, 1–13 (2021).
6. Liguori, I. et al. Oxidative stress, ageing, and diseases. Clin. Interv. Ageing 13, 757–772 (2018).
7. Lesjak, M. et al. Antioxidant and anti-inflammatory activities of quercetin and its derivatives. J. Funct. Foods 40, 68–75 (2018).
8. Xu, D., Hu, M. J., Wang, Y. Q. & Cui, Y. L. Antioxidant activities of quercetin and its complexes for medicinal application. Molecules 24, (2019).
9. Li, Y. et al. Quercetin, inflammation and immunity. Nutrients 8, 1–14 (2016).
10. Dong, Y. S. et al. Protective effect of quercetin against oxidative stress and brain edema in an experimental rat model of subarachnoid hemorrhage. Int. J. Med. Sci. 11, 282–290 (2014).
11. Heinz, S. A., Henson, D. A., Austin, M. D., Jin, F. & Nieman, D. C. Quercetin supplementation and upper respiratory tract infection: A randomized community clinical trial. Pharmacol. Res. 62, 237–242 (2010).
12. Nieman, D. C. et al. Quercetin reduces illness but not immune perturbations after intensive exercise. Med. Sci. Sports Exerc. 39, 1561–1569 (2007).
13. Shen, P. et al. Potential Implications of Quercetin in Autoimmune Diseases. Front. Immunol. 12, (2021).
14. Javadi, F. et al. The Effect of Quercetin on Inflammatory Factors and Clinical Symptoms in Women with Rheumatoid Arthritis: A Double-Blind, Randomized Controlled Trial. J. Am. Coll. Nutr. 36, 9–15 (2017).
15. Jafarinia, M. et al. Quercetin with the potential effect on allergic diseases. Allergy Asthma Clin Immunol 16, 36 (2020).
16. Serban, M. C. et al. Effects of Quercetin on Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J. Am. Heart Assoc. 5, (2016).
17. Patel, R. V. et al. Therapeutic potential of quercetin as a cardiovascular agent. Eur. J. Med. Chem. 155, 889–904 (2018).
18. Marunaka, Y. et al. Actions of Quercetin, a Polyphenol, on Blood Pressure. Molecules 22, (2017).
19. Rauf, A. et al. Anticancer potential of quercetin: A comprehensive review. Phyther. Res. 32, 2109–2130 (2018).
20. Reyes-Farias, M. & Carrasco-Pozo, C. The Anti-Cancer Effect of Quercetin: Molecular Implications in Cancer Metabolism. Int. J. Mol. Sci. 20, 3177 (2019).
21. Kusaczuk, M., Krętowski, R., Naumowicz, M., Stypułkowska, A. & Cechowska-Pasko, M. A Preliminary Study of the Effect of Quercetin on Cytotoxicity, Apoptosis, and Stress Responses in Glioblastoma Cell Lines. Int. J. Mol. Sci. 23, (2022).
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