Quercetin: The Super Antioxidant

Quercetin, Polyphenols and Health

Quercetin is an exciting, hotly researched type of naturally and widely occurring plant compound known as a flavonoid, which themselves are types of polyphenols.¹

Polyphenols are phytochemicals consisting of phenolic rings, and in plants are protective against biological and environmental stress².

Quercetin, perhaps the best researched of these compounds, possesses numerous pharmacological properties, such as being antiviral, anticancer, anti-proliferative, anti-diabetic, anti-aging, anti-inflammatory, neuroprotective, and of course, antioxidant^{1, 2, 7, 13}.

When compared with the better known antioxidants, vitamin C and E, the dietary flavonoids such as quercetin, kaempferol and apigenin are considered to be much more biologically effective^{1, 5}.

Flavonoids are also important for preventing platelet aggregation and lipid peroxidation, as well as enhancing mitochondrial biogenesis, the latter of which opens up many interesting therapeutic possibilities^{3, 10}.

Excitingly, due to the molecule's lipophilic properties, it can easily cross the blood-brain barrier and exert its protective effects inside the brain^{1, 6}.

Quercetin is used clinically in the treatment of allergies, arthritis, cardiovascular disorders, cancer, hypertension and inflammation, and research is ongoing in many areas, such as for epilepsy, sepsis, protection against neurodegenerative brain disorders like Alzheimer’s, and more^{1, 6, 7, 12}.

Quercetin as an Antioxidant

Oxidative stress is the excessive production of damaging molecules such as reactive oxygen species, eventually resulting in pathologies caused by a dysregulated oxidative-antioxidant balance.

Oxidative stress can contribute to mitochondrial DNA damage, lipid peroxidation, inflammation, apoptosis (cell death) of cardiac muscle, and intracellular protein denaturation.

Quercetin’s biological structure makes it a potent antioxidant and scavenger of reactive oxygen species, so it can effectively protect our bodies and even our mitochondria against damaging oxidative stress, as well as helping maintain oxidative balance.

It is able to regulate glutathione levels in the body, and has been shown to enhance superoxide dismutase, catalase and glutathione activity.

How Else Does Quercetin Improve Human Health?

However, quercetin does so much more than just reduce cellular oxidative damage.

For example, quercetin also appears to help modulate autophagy, that holy grail of antiaging, which is our body's self-cleaning process for eliminating damaged cells, with therapeutic benefits.

Quercetin also interacts directly with DNA as shown by many studies, however, it's yet to be elucidated whether it's protecting our DNA from oxidative damage, or perhaps even repairing previous damage.

Recent research shows quercetin has the ability to chelate excess iron from the body, which is not only highly oxidative and potentially DNA damaging, but is also required in large amounts for cancer cell proliferation, thereby adding to its therapeutic potential for a cancer therapy^{11, 15}.

What Are the Most Evidence-Based Applications for Quercetin?

Here are some short summaries of the most recent research compilations on quercetin.

Inflammation: A meta-analysis of randomized control trials in humans found significant reductions in circulating CRP, an inflammatory biomarker, in patients with a diagnosed disease⁸.

Rheumatoid Arthritis: A randomized control trial in women with rheumatoid arthritis showed reduced early morning and after-activity pain, significantly reduced tender joint counts, improved disease activity and general health assessment scores, as well as significantly reduced numbers of patients with active disease in the quercetin group. Plasma levels of tumor necrosis factor alpha were also significantly reduced in the quercetin group⁹.

Neuroprotection: A recent literature review on quercetin’s neuropharmacological effects revealed it can protect against neurotoxic chemicals, prevent and mitigate neuronal injuries as well as neurodegeneration, and appears to be strongly protective against many neurodegenerative diseases¹².

Diabetes: Quercetins' antihyperglycemic actions, such as improving insulin sensitivity, insulin resistance and promotion of glycogen synthesis, are all tied to its stimulation of pancreatic beta-cells, and offer much to be excited about on this front¹³.

Antiviral: Quercetin is being intensively studied for its very promising antiviral potential, which includes polymerase, reverse transcriptase & protease inhibition, DNA gyrase suppression, and binding of viral capsid proteins¹⁴.

How Can I Incorporate Quercetin Into My Diet & Enhance Absorption?

Quercetin occurs widely in the plant kingdom and in the human diet, with some of the richest commonly eaten sources being onions, grapes, cherries, apples, mangoes, citrus fruits, buckwheat, plums, tomatoes, and tea.

Common culinary spices, as well as popular herbal medicines, are particularly rich sources of quercetin, including fennel, turmeric, ashwagandha, amla, holy basil, licorice, gotu cola, St John’s wort, coriander & many more³.

Research into the absorption of quercetin in humans is ongoing, with mixed results, however it is generally assumed quercetin is absorbed easily due to its lipophilic nature, and increasing oral doses correlate to increased serum levels³.

A typical dietary intake in humans is 5-100 mg daily, but most clinical studies use 500 to 1000 mg per day in divided doses, and absorption can be enhanced by consuming quercetin in the presence of a fatty meal, or by taking it along with some lecithin, apple pectin, or oligosaccharides such as inulin^{4, 5}.

How is Quercetin Metabolized?

In food, quercetin is present as quercetin glycosides, which are hydrolyzed in the gut, releasing aglycone, which is then absorbed and metabolized into glucuronidated, methylated and sulfated complexes, which are more stable for circulation in the blood plasma^{14, 15}.

Researchers are now increasingly exploring the metabolism of quercetin, with interesting discoveries, such as methylated quercetin glucuronides located in liver cells, where its protection from local oxidative stress, and its activation of Nrf2 metabolic pathway in pancreatic tissues would greatly contribute to its anti-diabetic effects¹⁵.

Much more research is being conducted in this exciting space, so stay tuned for future updates!

References:

1. Wang, G., Wang, Y., Yao, L. et al. Pharmacological activity of quercetin: An updated review. Evidence-Based Complementary and Alternative Medicine, vol 2022, Article ID 3997190 https://doi.org/10.1155/2022/3997190
2. Maurya, D. & Maurya, P.K. Health Benefits of Quercetin in Age-Related Diseases. Molecules 2022, 27(8) https://doi.org/10.3390/molecules27082498
3. Randi L. Edwards, Tiffany Lyon, Sheldon E. Litwin, Alexander Rabovsky, J. David Symons, Thunder Jalili, Quercetin Reduces Blood Pressure in Hypertensive Subjects, The Journal of Nutrition, Volume 137, Issue 11, November 2007 https://doi.org/10.1093/jn/137.11.2405
4. Batiha, G.E.-S.; Beshbishy, A.M.; Ikram, M.; Mulla, Z.S.; El-Hack, M.E.A.; Taha, A.E.; Algammal, A.M.; Elewa, Y.H.A. The Pharmacological Activity, Biochemical Properties, and Pharmacokinetics of the Major Natural Polyphenolic Flavonoid: Quercetin. Foods 2020, 9, 374. https://doi.org/10.3390/foods9030374
5. Randi L. Edwards, Tiffany Lyon, Sheldon E. Litwin, Alexander Rabovsky, J. David Symons, Thunder Jalili, Quercetin Reduces Blood Pressure in Hypertensive Subjects, The Journal of Nutrition, Volume 137, Issue 11, November 2007, Pages 2405–2411 https://doi.org/10.1093/jn/137.11.2405
6. Kressler J, Millard-Stafford M, Warren GL. Quercetin and endurance exercise capacity: a systematic review and meta-analysis. Med Sci Sports Exerc. 2011 Dec;43(12):2396-404. doi: 10.1249/MSS.0b013e31822495a
7. Erratum in: Med Sci Sports Exerc. 2012 Mar;44(3):558-9. PMID: 21606866. https://doi.org/10.1093/jn/137.11.2405
8. Qian Deng, Xiao Xue Li, Yanting Fang, Xin Chen, Jingui Xue, "Therapeutic Potential of Quercetin as an Antiatherosclerotic Agent in Atherosclerotic Cardiovascular Disease: A Review", Evidence-Based Complementary and Alternative Medicine, vol. 2020, Article ID 5926381, 12 pages, 2020. https://doi.org/10.1155/2020/5926381
9. Qiaowen Ou, Zhifen Zheng, Yongyi Zhao & Weiqun Lin (2020) Impact of quercetin on systemic levels of inflammation: a meta-analysis of randomised controlled human trials, International Journal of Food Sciences and Nutrition, 71:2, 152-163, DOI: 10.1080/09637486.2019.1627515
10. Fatemeh Javadi, Arman Ahmadzadeh, Shahryar Eghtesadi, Naheed Aryaeian, Mozhdeh Zabihiyeganeh, Abbas Rahimi Foroushani & Shima Jazayeri (2017) 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, 36:1, 9-15, DOI: 10.1080/07315724.2016.1140093
11. Milad Ashrafizadeh, Zahra Ahmadi, Tahereh Farkhondeh & Saeed Samarghandian (2022) Autophagy as a molecular target of quercetin underlying its protective effects in human diseases, Archives of Physiology and Biochemistry, 128:1, 200-208, DOI: 10.1080/13813455.2019.1671458
12. Mingming Yin, Yongping Liu & Yi Chen (2021) Iron metabolism: an emerging therapeutic target underlying the anti-cancer effect of quercetin, Free Radical Research, 55:3, 296-303, DOI: 10.1080/10715762.2021.1898604
13. Islam MS, Quispe C, Hossain R, Islam MT, Al-Harrasi A, Al-Rawahi A, Martorell M, Mamurova A, Seilkhan A, Altybaeva N, Abdullayeva B, Docea AO, Calina D and Sharifi-Rad J (2021) Neuropharmacological Effects of Quercetin: A LiteratureBased Review. Front. Pharmacol. 12:665031. doi: 10.3389/fphar.2021.66503
14. Bahare Salehi, Laura Machin, Lianet Monzote, Javad Sharifi-Rad, Shahira M. Ezzat, Mohamed A. Salem, Rana M. Merghany, Nihal M. El Mahdy, Ceyda Sibel Kılıç, Oksana Sytar, Mehdi Sharifi-Rad, Farukh Sharopov, Natália Martins, Miquel Martorell, and William C. Cho. Therapeutic Potential of Quercetin: New Insights and Perspectives for Human Health. ACS Omega 2020 5 (20), 11849-11872 DOI: 10.1021/acsomega.0c01818
15. Di Petrillo, A., Orrù, G., Fais, A., & Fantini, M. C. (2022). Quercetin and its derivates as antiviral potentials: A comprehensive review. Phytotherapy Research, 36( 1), 266– 278. https://doi.org/10.1002/ptr.7309
16. Michala AS, Pritsa A. Quercetin: A Molecule of Great Biochemical and Clinical Value and Its Beneficial Effect on Diabetes and Cancer. Diseases. 2022 Jun 29;10(3):37. doi: 10.3390/diseases10030037. PMID: 35892731; PMCID: PMC9326669.