In an August 21, 2021, newsletter,1
Dr. Michael Murray discussed the use of quercetin for respiratory
infection symptoms. In November 2020, he’d suffered a “very mild and
brief bout of COVID-19.”
He also recounts an anecdotal story of a friend who developed
suspicious respiratory symptoms. His friend had been taking a number of
supplements said to offer protection, but was still feeling awful.
As it turns out, the one thing he’d not taken was quercetin, and as
soon as he did, that same day, his symptoms started to dissipate. This
experience, Murray says, “is consistent with the results from two
clinical trials” that were recently published.
Quercetin seems to be a safe, far less expensive, and
easier-to-obtain and it works by a similar mechanism, driving zinc into
the cells to stop viral replication.
Statistical Improvement in Clinical Outcomes
In the first study,2
42 COVID-19 outpatients were divided into two groups. One group of 21
patients received standard medical therapy consisting of analgesics and
an antibiotic (acetaminophen 500-milligram (mg) to 1,000-mg dose if body
temperature was higher than 37.5 degrees C — 99.5 F — with a maximum
daily dosage of 3 grams, and 500 mg azithromycin for three consecutive
days).
The other group of 21 patients received standard therapy plus the
equivalent of 600 mg of quercetin per day (divided into three doses) for
seven days, followed by another seven-day course of 400 mg of quercetin
per day (divided into two doses).
The quercetin was used with sunflower lecithin, which has been
demonstrated to increase absorption in the gut by as much as 20 times,
compared to pure quercetin formulations.
The main outcomes being evaluated
were virus clearance and symptoms. After one week of treatment, 16 of
the 21 patients in the quercetin group tested negative for SARS-CoV-2
and 12 reported that all symptoms had diminished.
In the standard care group, only two tested negative and four had
partially improved symptoms. By the end of Week 2, the five remaining
patients in the quercetin group tested negative. In the standard care
group, 17 of the 19 remaining patients tested negative and one had died.
“These results are impressive and hopefully additional studies will
be conducted on hospitalized patients to see how quercetin might be
helpful in more severe cases,” Murray wrote in his newsletter.
Can Quercetin Reduce Hospitalizations and Deaths?
The second study3
— a prospective, randomized, controlled and open-label trial — gave 152
COVID-19 outpatients a daily dose of 1,000 mg of quercetin for 30 days
to evaluate its adjuvant effects in the treatment of early symptoms and
the prevention of severe infection. According to the authors:
“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. It is suggested that a
double-blind, placebo-controlled study should be urgently carried out to
confirm the results of our study.”
Mechanisms of Action
As noted in the first study4
above, quercetin was chosen based on the fact that it has antiviral,
anti-blood clotting, anti-inflammatory and antioxidant properties, all
of which are important in the treatment of SARS-CoV-2 infection. In the
second study, more detailed mechanisms of action are reviewed. According
to the authors:5
“SARS-CoV-2 proteases, like 3-chymotrypsin-like
protease (3CLpro), papain-like pro-tease (PLpro), RNA-dependent RNA
polymerase, spike (S)protein and human angiotensin-converting enzyme 2
(hACE2) are considered possible targets for developing effective
anti-COVID-19 drugs.
Recently, molecular docking studies have suggested
the possible binding interaction of quercetin with the 3CLpro, PLpro,
and S-hACE2 complex. Some recent results, obtained by biophysical
techniques, appear to support the results of the molecular docking
studies.
Quercetin, a flavonol not naturally present in the
human body, is the most abundant polyphenol in fruits and vegetable and
is widely used as a dietary supplement to boost the immune system and
promote a healthy lifestyle.
Quercetin is characterized by three crucial
properties: antioxidant, anti-inflammatory and immunomodulatory. The
combination of these actions allows quercetin to be a potential
candidate to support all unhealthy conditions where oxidative stress,
inflammation and immunity are involved.”
Initially, quercetin gained attention because it’s a zinc ionophore,
meaning it shuttles zinc — which has well-known antiviral effects — into
your cells just like the drug hydroxychloroquine.
Some proposed the primary reason hydroxychloroquine and quercetin
worked was because of this feature. Of course, you also had to take zinc
along with either of them. To effectively act as a zinc ionophore, the
quercetin also needs vitamin C.
Since then, other studies, including the two reviewed here, have
shown quercetin has other actions that makes it useful against
SARS-CoV-2 as well. As reported by Murray in his newsletter:
“In particular, quercetin exerts significant
inhibition on the binding of specific spike proteins to ACE-2 receptors,
thereby blocking the ability of the virus to infect human cells.
Quercetin has also been shown to directly neutralize viral proteins the
are critical in the replication of SARS-CoV-2.”
In some studies, quercetin has also been shown to inhibit the release
of inflammatory cytokines, which could help alleviate infection-related
symptoms and suppress excessive inflammatory responses from occurring.
Its antioxidant effects may also help prevent tissue damage caused by
scavenging free radicals, thereby aiding in the recovery process of
viral infections.6
Quercetin’s Antiviral Properties
Quercetin’s antiviral properties have been attributed to three main 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
For example, research7
funded by the U.S. Defense Advanced Research Projects Agency (DARPA),
published in 2008, found it lowers your risk of viral illness such as
influenza and boosts mental performance following extreme physical
stress, which might otherwise undermine your immune function and render
you more susceptible to infections.
Here, cyclists who received a daily dose of 1,000 mg of quercetin in
combination with vitamin C (which enhances plasma quercetin levels8,9)
and niacin (to improve absorption) for five weeks were significantly
less likely to contract a viral illness after bicycling three hours a
day for three consecutive days, compared to untreated controls. While
45% of the placebo group got sick, only 5% of the treatment group did.
Quercetin Works Against Many Common Viruses
Before the COVID-19 pandemic struck, several studies had highlighted
quercetin’s ability to prevent and treat the common cold and seasonal
influenza.10,11,12,13,14,15,16,17,18 By attenuating oxidative damage, it also lowers your risk of secondary bacterial infections,19 which is actually the primary cause of influenza-related deaths.
Importantly, quercetin increases mitochondrial biogenesis in skeletal
muscle, which suggests part of its antiviral effects are due to
enhanced mitochondrial antiviral signaling.20 Quercetin also works against other viruses, as demonstrated in the following studies:
• A 1985 study found quercetin inhibits
infectivity and replication of herpes simplex virus type 1, polio-virus
type 1, parainfluenza virus type 3 and respiratory syncytial virus
(RSV).21
• A 2016 animal study22 found quercetin inhibited mouse dengue virus and hepatitis virus.
• Other studies have confirmed quercetin’s power to inhibit both hepatitis B23 and C24 infection.
• A March 2020 study25
found quercetin provides “comprehensive protection” against
Streptococcus pneumoniae infection, both in vitro and in vivo, primarily
by neutralizing pneumolysin (PLY),26 one of the toxins released from pneumococci that encourages S. pneumoniae infection to blossom in the first place.
Streptococcus pneumoniae is responsible not only for pneumonia, but
can also be involved in some ear and sinus infections, meningitis and
certain blood infections.27 As reported by the authors of this study:28
“The results indicated that quercetin significantly
reduced PLY-induced hemolytic activity and cytotoxicity via repressing
the formation of oligomers.
In addition, treatment with quercetin can reduce
PLY-mediated cell injury, improve the survival rate of mice infected
with a lethal dose of S. pneumoniae, alleviate the pathological damage
of lung tissue and inhibit the release of cytokines (IL-1β and TNF-α) in
bronchoalveolar lavage fluid.
Considering the importance of these events in
antimicrobial resistant S. pneumoniae pathogenesis, our results
indicated that quercetin may be a novel potential drug candidate for the
treatment of clinical pneumococcal infections.”
How Quercetin Combats Inflammation and Boosts Immunity
Aside from its antiviral activity, quercetin is also known for
boosting immunity and combating inflammation. As noted in a 2016 study29 in the journal Nutrients, mechanisms of action include (but is not limited to) the inhibition of:30
- Lipopolysaccharide (LPS)-induced tumor necrosis factor α (TNF-α)
production in macrophages. 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
- LPS-induced mRNA levels of TNF-α and interleukin (IL)-1α in glial
cells, which results in “diminished apoptotic neuronal cell death”
- The production of inflammation-producing enzymes
- Calcium influx into the cell, which in turn inhibits
pro-inflammatory cytokine release, as well as histamine and serotonin
release from intestinal mast cells31
According to this paper, quercetin also stabilizes mast cells, has
cytoprotective activity in the gastrointestinal tract, and “a direct
regulatory effect on basic functional properties of immune cells,” which
allows 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.”32
Bioavailability
While quercetin does have potent antiviral effects, in order for it
to work effectively you need sufficiently high dosages to raise the
level of quercetin in your body’s tissues.
The relatively low absorption rate of quercetin is why a sunflower lecithin formulation was used.
Research33
published in the July-December 2021 issue of the Journal of Natural
Health Products Research, found a quercertin matrix has the same total
absorption rate as quercetin phytosome — and higher peak blood levels.
“Since both of these forms of quercetin produce
similar blood levels, they should produce the same effects at equal
dosages based upon quercetin content,” Murray wrote in his newsletter, adding:
“My dosage recommendation as part of a nutritional supplement program to support immune function is 250 mg twice daily.
And in patients with active Infection, my
recommendation is … six capsules twice a day providing a total of 3,000
mg of quercetin. This high dosage should be taken for at least 10 days
and then reduced to a maintenance dosage of 250 mg twice daily …
[This] high dosage may not be necessary. But my
dosage calculations are based upon likely tissue concentrations needed
to exert the strongest antiviral effects. And given the safety of
quercetin, there is no harm at this level.”
Protocol Using Quercetin
One doctor who early brought quercetin into the limelight was Dr.
Vladimir Zelenko. As hydroxychloroquine became difficult to obtain,
Zelenko switched to recommending quercetin instead, as it’s readily
available as an over-the-counter supplement. For a downloadable “cheat
sheet” of Zelenko’s protocol for COVID-19, visit VladimirZelenkoMD.com.
Other Health Benefits of Quercetin
There are also other lesser known benefits and uses for quercetin, including the prevention and/or treatment of:34
High blood pressure35,36 |
Cardiovascular disease37 |
Obesity38 and metabolic syndrome39
(a cluster of conditions including high blood pressure, high blood
sugar, high triglyceride levels and fat accumulation around the waist
that raise your risk for Type 2 diabetes, heart disease and stroke) |
Certain kinds of cancer, in particular leukemia, and to a lesser degree breast cancer40 |
Nonalcoholic fatty liver disease (NAFLD)41 |
Gout42 |
Arthritis43 |
Mood disorders44 |
Aluminum-induced neurodegenerative changes, such as
those seen in Alzheimer’s, Parkinson’s and amyotrophic lateral sclerosis
(ALS).45 |
Longevity, thanks to its senolytic benefits (clearing out damaged and worn-out cells)46,47 |
Research has also highlighted quercetin’s epigenetic influence and ability to:48
- Interact with cell-signaling pathways
- Modulate gene expression
- Influence the activity of transcription factors
- Modulate microRNAs
MicroRNAs used to be considered "junk" DNA. But far from being
useless, research has revealed so-called "junk" DNA is actually microRNA
and plays a crucial role in regulating genes that make the proteins
that build your body.
The microRNA function as "on/off" switches for the genes. Depending
on the microRNA input, a single gene can code for any of more than 200
protein products. Quercetin’s ability to module microRNA may also help
explain its cytotoxic effects, and why it appears to improve cancer
survival (at least in mice).
