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Quercetin is a natural compound found in plant foods. It has received much attention over the last few years in particular, because of the supportive and regulatory roles it has to play in immune function. In this article, we take a closer look at what quercetin actually is, how you can get more in your diet and how it can help to support immune health.

Quercetin – What is it?
Quercetin is a naturally-occurring flavonoid found in plant foods. Flavonoids belong to a family of plant compounds known as polyphenols. They are remarkable tiny compounds that can help to protect plants from stressors (e.g. insects / fungi / wind / heat), act as UV filters and signalling molecules, detoxify harmful substances and work as antimicrobial defence compounds too. The great news is that when we consume flavonoids from plant foods, we get to benefit from these incredible properties too!  Read more about this here. There are over 5,000 varieties of flavonoids that we know of, and likely many more that we don’t.  All of the different varieties of flavonoids have slightly different health benefits to impart, and that’s why getting a diverse variety of plants in your diet each day is so very important.

Quercetin – Best sources
Quercetin is considered to be one of the most abundant flavonoids in the human diet. Some of the best sources of quercetin are apples, onions, berries, capers, red grapes, cherries, citrus fruits, cruciferous vegetables, leafy green vegetables, tomatoes, garlic, ginger, red wine, black tea and green tea.

Onions are generally considered to rank highest in terms of quercetin content. Interestingly, one study found the levels of quercetin in red onions to be 14-fold higher than in garlic, and 2-fold higher than white onions. Another study found the amount of quercetin in onion peel to be 48-fold more than the flesh.1-3

Levels of quercetin in foods are affected by storage, preparation and even the original growing conditions. Light stimulates the production of quercetin and studies have shown higher levels of quercetin in plants exposed to a greater amount of UV-radiation, adding weight to the theory that quercetin is produced by plants as a defence mechanism against UV exposure.4 Interesting then to consider that an apple picked from the top of a fruit tree might contain more quercetin than one picked from the lower branches covered in shade!

Quercetin – How does it support immune health?
Along with other flavonoids, quercetin has been shown to have antiviral, antimicrobial, antioxidant, anti-proliferative and anti-allergic effects. One of the most common reasons people turn to quercetin is to help with symptoms of seasonal allergic rhinitis (hayfever). Several studies have found quercetin to be a useful anti-inflammatory support and to improve survival and decrease cell damage in a mouse model of sepsis.5-7

Quercetin’s role in immune health has made it a topic of heightened interest certainly over the past few years, as much attention has been given to natural substances that have the potential to modulate the immune response. More specifically, the Sars-CoV-2 virus has been shown to activate the NLRP3 inflammasome – a part of the innate immune system which may lead to uncontrolled release of pro-inflammatory cytokines, ‘cytokine storm’, and potentially to severe damage of the respiratory epithelium.8 Therefore, natural compounds that have the potential to regulate the NLRP3 inflammasome are of significant scientific interest.

In a 2016 review article entitled Natural compounds as regulators of NLRP3 inflammasome-mediated IL-beta production’, the authors noted that “EGCG (epigallocatechin gallate) and quercetin are potent inhibitors of NLRP3 inflammasome-mediated IL-beta production, typically acting at more than one element of the involved pathways.”9 Numerous studies have demonstrated regulatory effects of specific dietary flavonoids including dihydroquercetin, quercetin, myricetin and apigenin on NLRP3 inflammasome activation.10-13

Quercetin has also been studied for its potential role in autoimmune health problems, including rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and systemic lupus erythematosus. In a recent review published in June 2021 in Frontiers of Immunology, the authors explored the ‘Potential implications of quercetin in autoimmune diseases’ and reported that quercetin shows much promise in this area, especially given that it is generally safe and well tolerated. Whilst many of quercetin’s underlying mechanisms have been reported in animal models and need to be backed by human clinical studies, the authors concluded that, “quercetin will be expected to become a potential opportunity and supplement for the treatment and prevention of autoimmune diseases”.14

It is these demonstrated immune regulatory roles that make quercetin such a powerful plant compound to consider for immune support.

Harnessing the power of natural plant compounds
Supporting optimal immune health involves bringing together many different diet and lifestyle factors. You can read more about these here in our comprehensive Immune Health Fact Sheet. With each new day, we learn even more about the powerful compounds that are present in our food and the fascinating ways in which they may enhance our immune resilience. Quercetin is one such compound that has the potential to deliver comprehensive health benefits, especially for immune function and regulation, and it certainly makes sense to consider optimising your daily intake.

References:
1. Kwak JH, Seo JM, et al. Variation of quercetin glycoside derivatives in three onion (Allium cepa L.) varieties. Saudi J Biol Sci. 2017 Sep; 24(6): 1387-1391
2. Hertog M.G.L., Hollman P.C.H., et al. Optimization of a quantitative HPLC determination of potentially anticarcinogenic flavonoids in vegetables and fruits. J. Agric. Food Chem. 1992; 40: 1591–1598
3. Gorinstein S., Leontowicz H., et al. Comparison of the main compounds and antioxidant activities in garlic and white and red onion after treatment protocols. J. Agric. Food Chem. 2008; 56(12): 4418–4426.
4. Azarafshan M, Peyvandi M, et al. The effects of UV-B radiation on genetic and biochemical changes of Pelargonium graveolens L’Her. Physiol Mol Biol Plants. 2020 Mar; 26(3): 605-616
5. Comalada M, Camuesco D, et al. In vivo quercetin anti-inflammatory effect involves release of quercetin, which inhibits inflammation through down-regulation of the NF-kappaB pathway. Eur J Immunol 2005 Feb; 35(2): 584-92 25.
6. Zhu Y, Fan S et al. Quercetin confers protection of murine sepsis by inducing macrophage M2 polarization via the TRPM2 dependent calcium influx and AMPK/ATF3 activation. Journal of Functional Foods. Volume 56, May 2019, Pages 1- 13. 26.
7. Cui W, Hu G et al. Quercetin Exerted Protective Effects in a Rat Model of Sepsis via Inhibition of Reactive Oxygen Species (ROS) and Downregulation of High Mobility Group Box 1 (HMGB1) Protein Expression. Med Sci Monit. 2019 Aug 4; 25: 5795- 5800
8. Chen IY, Moriyama M, et al. Severe acute respiratory syndrome coronavirus viroporin 3a activates the NLRP3 inflammasome. Front Microbiol. 2019; 10: 50.
9. Tozsér J, Benko S. Natural compounds as regulators of NLRP3 inflammasome-mediated IL-1Beta production. Mediators Inflamm. 2016; 2016: 5460302.
10. Lim H, Min DS, et al. Flavonoids interfere with NLRP3 inflammasome activation. Toxicology and Applied Pharmacology. 28 June 2018
11. H. Dabbagh-Bazarbachi. Zinc ionophore activity of quercetin and epigallocatechin-gallate: from hepa 1-6 cells to a liposome model. J Agric Food Chem, 62 (32) (2014), pp. 8085-8093
12. T. Ding, et al. Kidney protection effects of dihydroquercetin on diabetic nephropathy through suppressing ROS and NLRP3 inflammasome. Phytomedicine (41) (2018), p. 45
13. J.-Y. Choe, et al. Quercetin and ascorbic acid suppress fructose-induced NLRP3 inflammasome activation by blocking intracellular shuttling of txnip in human macrophage cell lines. Inflammation, 40 (3) (2017), p. 980

14. Shen P, Lin W, et al. Potential implications of quercetin in autoimmune diseases. Front Immunol 2021; 12: 689044
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