The Substack Modern Discontent recently posted an anthology series on the benefits of quercetin,1
including the finding that it works like hydroxychloroquine, a drug
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, red leaf lettuce, strawberries,
raspberries, blueberries, cranberries, black currants and green tea.
The quercetin content in any given food is largely dependent on light
exposure, though, so depending on the country you’re in, different
foods will top the list of most quercetin-rich. General mechanisms of
action of this nutrient include:3
Antioxidant activity — 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 activity — This is in part responsible for quercetin’s cardiovascular benefits |
Inhibition of platelet aggregation |
Anti-allergy activities (inhibits release of histamine and other allergic substances) |
Immunomodulation |
Anticancer activity |
Antiviral activity — It’s been found to reduce
replication of many viruses, including HIV, hepatitis C, enterovirus 71,
porcine epidemic diarrhea virus and SARS-CoV-2, by targeting the
proteases in these viruses |
Zinc ionophore — Quercetin helps zinc enter your cells. Zinc, in turn, has potent antiviral activity |
Quercetin Against SARS-CoV-2
In Part 24
of the anthology, Modern Discontent reviews the evidence behind the
recommendation to use quercetin against COVID-19 specifically. As
mentioned, zinc has antiviral activity, and quercetin helps shuttle the
zinc into the cell. But quercetin also has other mechanisms of action
that make it useful in the fight against COVID-19.
For example, quercetin has been shown to:
Inhibit SARS-CoV-2 spike protein to ACE2 receptor docking.5,6,7
Computational modeling studies have shown quercetin can bind to the
ACE2 receptor and the spike protein interface, thereby inhibiting the
two from binding together. By preventing viral attachment, it helps
prevent viral entry into the cell. Commenting on one of these studies,
Modern Discontent notes:8
“Although [a] computer modeled study,9
the evidence here suggests that quercetin’s binding activity to ACE2 is
comparable to other standard of care drugs used to treat SARS-CoV-2
(eg. Remdesivir, Lopinavir, Ritonavir).”
|
Inhibit lipopolysaccharide (LPS)-induced tumor necrosis factor α (TNF-α) production in macrophages.10
(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.11 |
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.”12 |
Act as a zinc ionophore, i.e., a compound that shuttles zinc into your cells.13
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)14
— 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),15
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.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. Within Type 1 interferon, there
are alpha and beta. Type 2 interferon has the gamma form.18
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 NLRP3 inflammasome, an immune system
component involved in the uncontrolled release of proinflammatory
cytokines that occurs during a cytokine storm.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:
- Binding to the spike protein, thereby inhibiting its ability to infect host cells23
- Inhibiting replication of already infected cells
- Reducing infected cells’ resistance to treatment with antiviral medication
|
Inhibit the SARS-CoV-2 main protease.24 |
The Front Line Critical COVID-19 Care Alliance (FLCCC) early treatment protocol25
includes quercetin at a dose of 250 milligrams twice a day, in
combination with 100 mg elemental zinc and 500 mg to 1,000 mg of vitamin
C twice a day.
Quercetin in COVID-19 Medical Literature
In Part 3,26 Modern Discontent reviews some of the clinical trials that have taken place. One COVID-19-specific study27
found that people who took zinc and two zinc ionophores — quinine drops
and quercetin — had lower incidence of COVID-19 than the control group.
Over the course of the study (20 weeks), only two of the 53 test
subjects became symptomatic, compared to 12 of the 60 controls. As noted
by Modern Discontent:28
“Although this didn’t test quercetin in isolation,
the study does suggest that over-the-counter, easily accessible
compounds may be extremely beneficial in fighting against COVID,
especially when taken as a prophylactic.”
In another trial,29
76 outpatients who tested positive but had only mild symptoms were
given 1,000 mg of Quercetin Phytosome® (quercetin in sunflower
phospholipids that increase oral absorption 20-fold) per day for 30
days, in addition to standard care (analgesics, oral steroids and
antibiotics). Another 76 patients were given standard of care only.
In the quercetin group, only 9.2% of participants went on to require
hospitalization, compared to 28.9% of patients who received standard of
care only. According to the authors:30
“The results revealed a reduction in frequency and
length of hospitalization, in need of non-invasive oxygen therapy, in
progression to intensive care units and in 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 agent and
in combination with standard care, when used in early stage of viral
infection, could aid in improving the early symptoms and help in
preventing the severity of COVID-19 disease.”
Quercetin was also featured in two scientific reviews published in 2020.31 The first, published in in the Integrative Medicine journal in May 2020,32 highlighted quercetin’s promotion of SIRT2, which inhibits NLRP3 inflammasome.
The second review article,33
published in the June 19, 2020, issue of Frontiers in Immunology,
highlighted quercetin’s usefulness as a COVID-19 treatment when used in
conjunction with vitamin C. The vitamin C recycles oxidized quercetin,
producing a synergistic effect. It also enhances quercetin’s antiviral
capacity.
Food as Medicine
With the advent of processed foods, many important nutrients have
been lost or minimized in the average person’s diet. Quercetin, being
found in fresh fruits, vegetables and berries is one of them.
Unfortunately, while essential vitamins and minerals are generally
recognized for their importance, antioxidants such as quercetin are
often overlooked, and sometimes labeled as “pseudoscience” or “fad”
supplements. As noted by Modern Discontent:
“The great number of benefits that these compounds
contribute to humans cannot be overstated ... An argument can be made
that not only could quercetin prove beneficial to our health, but an
absence of it may prove detrimental in the long term.”
If COVID-19 has taught us anything, it’s the importance of basic
health and a healthy immune function. In this regard, a diet high in
fresh fruits and vegetables can go a long way. Nutritional supplements
also have their place, especially in situations like a pandemic.
Summary
In conclusion, Modern Discontent provides the following summary of findings:34
• “There’s evidence that quercetin may work similarly to hydroxychloroquine —
It seems that quercetin may operate as both an immunomodulator and a
zinc ionophore. Its use as an over-the-counter anti-allergic supplement
as well as its use for asthma indicates an ability to affect the
production of histamine and cytokines ...
• Quercetin has plenty of other benefits —
... Antioxidants ... are some of the most well studied compounds, with
possible anti-cancer, pro-heart and pro-organ benefits. Add on possible
antimicrobial properties and it becomes hard to argue that this is
nothing more than a possible fad supplement.
• 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 main protease of SARS-CoV2 may be good target candidates for
quercetin ... the limited number of studies suggest quercetin may be
effective, especially if used early on or as a prophylactic.
• Dietary quercetin is the
main source of quercetin, and its deficiency in modern diets may be
contributing to our health problems — Quercetin is primarily
sourced from colorful fruits, vegetables, teas ... all foods that many
of our ancestors would have consumed on a regular basis ... Modern
‘enriched’ foods tend to supplement with additional vitamins and
minerals, but may miss out on other plant-derived compounds that have
played a substantial role in our diet.
Similar to reduced sunlight exposure and the need for increased
vitamin D supplementation, we may need to look at possible
supplementation of overlooked compounds such as polyphenols. Sourcing
these compounds from real foods would prove the most beneficial, but in
groups of people who may not have access to fresh fruits and vegetables,
quercetin and polyphenol supplementation may be useful.
This would include people with alternative diets such as keto,
who may avoid high carb fruits, and thus may be missing a key nutrient
in their diets.
Quercetin has plenty of benefits, and for those who may be
missing out on it in their diet they may want to look into sourcing it
with supplementation. Don’t take this as a prescription or
recommendation, but an argument to examine your own health and see what
you may be lacking ...”
