Quercetin – An alternative to hydroxychloroquine and more

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Substack Modern Discontent recently published an anthology series on the benefits of quercetin,1 including the finding that it acts like hydroxychloroquine, a drug that has been found to be effective against SARS-CoV-2 when used early enough.

Part 12 begins with a brief overview of what quercetin is and its basic mechanisms of action. Quercetin is a flavonoid found in a variety of fruits and vegetables such as onions and shallots, apples, broccoli, asparagus, green peppers, tomatoes, lettuce, strawberries, raspberries, blueberries, cranberries, black currants and green tea.

The content of quercetin in any food largely depends on exposure to light, however, depending on the country you are in, different foods will be at the top of the list of the richest in quercetin. General mechanisms of action of this nutrient include:3

Antioxidant action – Antioxidants help prevent oxidative damage from harmful reactive oxygen species (ROS). Quercetin acts as a free radical scavenger, and its activity can be further enhanced by vitamin C.

Anti-inflammatory action – is partly responsible for the cardiovascular benefits of quercetin

Inhibition of platelet aggregation

Antiallergic activities (inhibits the release of histamine and other allergic substances)

Immunomodulation

Anticancer activity

Antiviral activity – Decreased replication of many viruses, including HIV, hepatitis C, enterovirus 71, swine diarrhea virus and SARS-CoV-2, found to target proteases in these viruses

Zinc ionophore – quercetin helps zinc enter your cells. Zinc, on the other hand, has a strong antiviral effect

Quercetin against SARS-CoV-2

In Part 24 anthology, Modern Discontent considers the evidence behind the recommendation to use quercetin specifically against COVID-19. As mentioned, zinc has antiviral activity, and quercetin helps transfer zinc to the cell. But quercetin has other mechanisms of action that make it useful in the fight against COVID-19.

For example, quercetin has been shown to:

Inhibition of SARS-CoV-2 protein binding to the ACE2 receptor.5,6,7 Computer modeling studies have shown that quercetin can bind to the ACE2 receptor and the spike protein interface, thereby inhibiting their interconnection. By preventing the virus from binding, it helps prevent the virus from entering the cell. Commenting on one of these studies, Modern Discontent notes:8

“Although [a] computer modeled study,9 evidence here suggests that the binding activity of quercetin to ACE2 is comparable to other standard drugs used to treat SARS-CoV-2 (e.g., Remdesivir, Lopinavir, Ritonavir).

They inhibit the production of tumor necrosis factor α (TNF-α) in lipopolysaccharide-induced macrophages (LPS).10 (TNF-α is a cytokine involved in systemic inflammation and secreted by activated macrophages, a type of immune cell that digests foreign substances, microbes, and other harmful or damaged components.)

They inhibit the release of proinflammatory cytokines and histamines by modulating calcium influx into the cell.11

It stabilizes mast cells and regulates the basic functional properties of immune cells, thus allowing them to “inhibit a huge range of molecular targets in the range of micromolar concentrations, either by reducing or suppressing many inflammatory pathways and functions”.12

It acts as a zinc ionophore, ie a compound that carries zinc to your cells.13 This is one of the mechanisms that may explain the effectiveness of hydroxychloroquine, which is also a zinc ionophore.

Enhance interferon response to viruses, including SARS-CoV-2, by inhibiting casein kinase II (CK2) expression14 – CK2 is an enzyme that is fundamental for controlling homeostasis at the cellular level. There is evidence that it reduces the ability of a cell to generate type 1 interferon when attacked by a virus.

It does this by inhibiting retinoic acid inducible gene I (RIG-I),15 which has protein sensors that signal the genetic expression of type 1 interferon by identifying replication of RNA viruses, such as SARS-CoV-2. Quercetin inhibits CK2 expression, which slows RNA replication.16

Interferons are a subset of cytokines discovered in 1957.17 These cells are often the initial defense against viruses. There are two types and three forms of interferon. There are alpha and beta inside interferon type 1. Interferon type 2 has a gamma shape.18

Different types are based on cytokine function. Type 1 interferons help cells resist viruses. Type 2 helps respond to infections and cancer growth. The name “interferon” comes from the ability of type 1 to interfere with the ability of the virus to duplicate. The cell secretes interferons when a foreign substance, such as a virus, is detected.

However, interferon does not work by attacking the virus. Instead, it tells the infected cell and the cells surrounding the infected cell to make proteins that stop the virus from replicating. In short, quercetin prevents CK2 from interfering with the action of type 1 interferon so that cells receive a signal to stop virus replication.

Modulate with inflammation NLRP3, a component of the immune system involved in the uncontrolled release of pro-inflammatory cytokines that occurs during a cytokine storm.19

It has a direct antiviral effect against SARS-CoV20,21,22 – The general antiviral capacity of quercetin is attributed to three primary mechanisms of action:

  1. Binding to the spiky protein, thereby inhibiting its ability to infect host cells23
  2. Inhibition of replication of already infected cells
  3. Decreased resistance of infected cells to treatment with antiviral drugs

They inhibit the major protease SARS-CoV-2.24

Early Treatment Protocol Front Line Critical COVID-19 Care Alliance (FLCCC).25 includes quercetin at a dose of 250 milligrams twice daily, in combination with 100 mg of elemental zinc and 500 mg to 1,000 mg of vitamin C twice daily.

Quercetin in the medical literature on COVID-19

In Part 3,26 Modern Discontent reviews some of the clinical trials that have taken place. One study specific to COVID-1927 found that people taking zinc and two zinc ionophores – quinine drops and quercetin – had a lower incidence of COVID-19 than the control group. During the study (20 weeks), only two of the 53 subjects tested became symptomatic, compared with 12 of the 60 controls. As noted by Modern Discontent:28

“Although this has not tested quercetin in isolation, the study suggests that readily available over-the-counter compounds can be extremely useful in combating COVID, especially when taken as prophylactics.”

In the second trial,29 76 outpatients who were positive but had only mild symptoms received 1000 mg of Quercetin Phytosome® (quercetin in sunflower phospholipids that increase oral absorption 20-fold) daily for 30 days, with standard care, analgesics, oral steroids and antibiotics). Another 76 patients received only standard care.

In the quercetin group, only 9.2% of participants required hospitalization, compared with 28.9% of patients receiving only standard care. According to the authors:30

“The results revealed a reduction in the frequency and length of hospitalizations, the need for non-invasive oxygen therapy, progression to intensive care units, and the number of deaths.

The results also confirmed the very high safety profile of quercetin and suggested possible anti-fatigue and pro-appetite properties. QP [Quercetin Phytosome®] is a safe remedy and in combination with standard care, when used in the early stages of viral infection, can help improve early symptoms and help prevent the severity of COVID-19 disease. ”

Quercetin was also presented in two scientific reviews published in 2020.31 The first, published in the journal Integrative Medicine in May 2020.32 highlighted the promotion of quercetin SIRT2, which inhibits NLRP3 inflammation.

Second review article,33 published in Frontiers in Immunology on June 19, 2020, highlighted the usefulness of quercetin as an anti-COVID-19 drug when used in conjunction with vitamin C. Vitamin C recycles oxidized quercetin, creating a synergistic effect. It also increases the antiviral capacity of quercetin.

Food as medicine

With the advent of processed foods, many important nutrients are lost or minimized in the diet of the average person. Quercetin, found in fresh fruits, vegetables and berries, is one of them. Unfortunately, while essential vitamins and minerals are generally recognized for their importance, antioxidants like quercetin are often overlooked, and are sometimes referred to as “pseudoscience” or “fad” supplements. As noted by Modern Discontent:

“The many benefits that these compounds contribute to humans cannot be overestimated … It can be argued that not only could quercetin prove beneficial to our health, but its deficiency could prove harmful in the long run.”

If COVID-19 has taught us anything, it is the importance of basic health and healthy immune function. In that sense, a diet rich in fresh fruits and vegetables can help a lot. Dietary supplements also have their place, especially in situations like a pandemic.

Abstract

In conclusion, Modern Discontent provides the following summary of findings:34

“There is evidence that quercetin may act similarly to hydroxychloroquine – Quercetin appears to act as both an immunomodulator and a zinc ionophore. Its use as an anti-allergic supplement without a prescription, as well as its use for asthma indicates the ability to affect the production of histamine and cytokines …

Quercetin has many other benefits – … Antioxidants … are some of the best-studied compounds, with potential anti-cancer, for heart and organ benefits. Add possible antimicrobial properties and it becomes difficult to claim that this is nothing more than a possible fashion accessory.

Although limited, there is some evidence that quercetin may be effective against SARS-CoV2 – Computer models and in vitro studies suggest that ACE2 receptors and the major protease SARS-CoV2 may be good target candidates for quercetin … a limited number of studies suggest that quercetin may be effective, especially if used early or as a prophylactic.

Dietary quercetin is the main source of quercetin, and its lack in the modern diet can contribute to our health problems – Quercetin is primarily obtained from colorful fruits, vegetables, teas … all foods that many of our ancestors would regularly consume … Modern ‘fortified’ foods tend to be supplemented with additional vitamins and minerals, but may miss other compounds of plant origin that have played a significant role. role in our diet.

Similar to reduced exposure to sunlight and the need for increased vitamin D supplementation, we may need to consider the possible supplementation of neglected compounds such as polyphenols. Obtaining these compounds from real food would prove most beneficial, but in groups of people who may not have access to fresh fruits and vegetables, quercetin and polyphenol supplements may be helpful.

This would include people with an alternative diet such as keto, who could avoid fruits high in carbohydrates and therefore may be lacking a key nutrient in their diet.

Quercetin has many benefits, and for those who may be missing it in their diet, they may want to look for it with supplementation. Do not take this as a recipe or a recommendation, but as an argument to examine your own health and see what you may be missing … ”

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