Have You Learned about Quercetin?

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In December of 2021, I asked you, “Do You Take Vitamins Zinc, D, C, and Quercetin?” No doubt you are familiar with zinc and vitamins D and C, but have you learned about quercetin? On his blog, Mercola.com, Dr. Joseph Mercola explains why quercetin is a supplement you should consider for your daily regimen. He writes:

I’ve previously reviewed the similarities between the flavonoid quercetin and the drug hydroxychloroquine, discussing the possibility of using quercetin in lieu of the drug against COVID-19. We’re now also starting to see quercetin mentioned more often in the scientific literature on COVID-19.

Quercetin Highlighted in COVID-19 Medical Literature

For example, a review article¹ published in the June 19, 2020, issue of Frontiers in Immunology highlights quercetin’s usefulness as a COVID-19 treatment, especially in conjunction with vitamin C. Quercetin is also featured in a review² of emerging COVID-19 research published in the Integrative Medicine journal. As reported by MedPage Today:³

“Quercetin … promotes SIRT2, which then inhibits the NLRP3 inflammasome assembly involved with COVID-19 infection, said Samuel F. Yanuck, DC, of the Program on Integrative Medicine at the University of North Carolina Chapel Hill School of Medicine, who co-authored a review⁴ of emerging research on the subject. It also plays a role in facilitating zinc transportation across lipid membranes, Yanuck said.

‘It’s not a bizarre or experimental substance and given it has these potential important biological roles, I think it’s worth being considered as part of an overall strategy,’ Yanuck told MedPage Today, adding that quercetin would need to be one part of a multifactorial treatment regimen …

COVID-19 has been associated with high levels of interleukin-6, depleted levels of interferons, and a cytokine storm that damages the body and is related to respiratory failure, said Ruben Colunga Biancatelli, MD, of Old Dominion University in Norfolk, Virginia, and first author of a paper on quercetin and vitamin C as a potential therapy for treating SARS-CoV-2 in Frontiers in Immunology.⁵

Using this rationale, researchers are postulating that vitamin C should be administered with quercetin because it can recycle oxidized quercetin, producing a synergistic effect and enhancing quercetin’s antiviral capability, Biancatelli added.”

Why Quercetin May Offer Hope Against COVID-19

There are solid reasons to suspect quercetin can be effective against SARS-CoV-2, the virus that causes COVID-19 disease. For example, quercetin has been shown to:

Bind to the spike protein of SARS-CoV (the virus responsible for severe acute respiratory syndrome or SARS), thereby inhibiting its ability to infect host cells.6 Using the supercomputer SUMMIT, researchers at Oak Ridge National Lab also identified quercetin as one of the molecules that might inhibit the SARS-CoV-2 spike protein from interacting with human cells.7,8

Inhibit lipopolysaccharide (LPS)-induced tumor necrosis factor α (TNF-α) production in macrophages.9 (TNF-α is a cytokine involved in systemic inflammation, secreted by activated macrophages, a type of immune cell that digests foreign substances, microbes and other harmful or damaged components.)

Inhibit the release of proinflammatory cytokines and histamine by modulating calcium influx into the cell.10

Stabilize mast cells and regulate the basic functional properties of immune cells, thereby allowing it to inhibit “a huge panoply of molecular targets in the micromolar concentration range, either by down-regulating or suppressing many inflammatory pathways and functions.”11

Act as a zinc ionophore, i.e., a compound that shuttles zinc into your cells.12 This is one of the mechanisms that can account for the effectiveness seen with hydroxychloroquine, which is also a zinc ionophore.

Boost interferon response to viruses, including SARS-CoV-2, by inhibiting the expression of casein kinase II (CK2)13 — CK2 is an enzyme that is fundamental to controlling homeostasis at the cellular level. There is evidence that it down-regulates the ability a cell has to generate Type 1 interferon when attacked by a virus. It does this by inhibiting retinoic acid-inducible gene I (RIG-I),14 which has protein sensors that signal genetic expression of type 1 interferon by identifying the replication of RNA viruses, such as SARS-CoV-2. Quercetin inhibits the expression of CK2, which slows the replication of RNA viruses.15 Interferons are a subset of cytokines discovered in 1957.16 These cells are often the initial defense against viruses. There are two types and three forms of interferon. Within Type 1 interferon, there are alpha and beta. Type 2 interferon has the gamma form.17 The different types are based on the function of the cytokine. Type 1 interferons help cells resist viruses. Type 2 aids in responding to infections and cancer growth. The name “interferon” came from the ability of Type 1 to interfere with the virus’s ability to duplicate. A cell secretes interferons when a foreign substance, like a virus, is detected. However, the interferon does not function by attacking the virus. Instead, it tells the infected cell and the cells that surround the infected cell to make proteins that stop viral replication. In a nutshell, quercetin stops CK2 from interfering with the action of Type 1 interferon so cells receive the signal to stop viral replication.

Modulate the NLRP3 inflammasome, an immune system component involved in the uncontrolled release of proinflammatory cytokines that occurs during a cytokine storm.18

Prevent a wide variety of dangerous viruses from entering cells, including Ebola.19

Exert a direct antiviral activity against SARS-CoV20,21,22 — Quercetin’s general antiviral capacity has been attributed to three primary mechanisms of action: Inhibiting the virus’ ability to infect cells Inhibiting replication of already infected cells Reducing infected cells’ resistance to treatment with antiviral medication

Inhibit the SARS-CoV-2 main protease.23

Quercetin Studied as COVID-19 Treatment and Prophylaxis

As reported by MedPage Today,²⁴ Dr. Hasan Önal is currently conducting an open-label nonrandomized trial²⁵ on quercetin in Turkey. COVID-19 patients are given 1,000 milligram (mg) of quercetin per day as an active treatment, while front-line health care workers are receiving 500-mg doses as a prophylaxis. As noted by the researchers:²⁶

“Quercetin is reported to be effective on treatment and prophylaxis of other SARS like coronavirus infections, as a strong antioxidant and scavenger flavonoid without any adverse events. Upon this data, the investigators hypothesize that quercetin can be effective on both prophylaxis and treatment of COVID-19 cases. Therefore, the aim of this study to evaluate the possible role of quercetin on prophylaxis and treatment of COVID-19.”