Vitamin C and
quercetin have synergistic effects that make them useful in the
prevention and early at-home treatment of COVID-19. Both are part of the
MATH+ protocol developed by the Front Line COVID-19 Critical Care
Working Group (FLCCC)
For COVID-19 prophylaxis, the FLCCC recommends vitamin C, quercetin, zinc, melatonin and vitamin D3
The at-home
treatment for mildly symptomatic patients is very similar to the
prophylactic regimen, but adds several optional drugs, including
aspirin, famotidine (an antacid) and ivermectin (a heartworm medication
that has been shown to inhibit SARS-CoV-2 replication in vitro)
The in-hospital
MATH+ protocol calls for intravenous methylprednisone, high-dose
ascorbic acid (vitamin C), thiamine and heparin. Optional additions
include melatonin, zinc, vitamin D3, atorvastatin, famotidine and
magnesium
There are two
distinct phases or stages of COVID-19 — the viral replication stage and
the immune dysfunction stage — and the treatment must be appropriate for
the stage you’re in. Equally crucial is starting aggressive treatment
as early as possible
Quercetin was initially found to
provide broad-spectrum protection against SARS coronavirus in the
aftermath of the SARS epidemic that broke out across 26 countries in
2003.1,2,3
Now, some doctors are advocating its use against SARS-CoV-2, in
combination with vitamin C, noting that the two have synergistic
effects.
Incidentally, ascorbic acid (vitamin C) and the bioflavonoid
quercetin (originally labeled vitamin P) were both discovered by the
same scientist — Nobel prize winner Albert Szent-Györgyi.4,5 Quercetin’s antiviral capacity has been attributed to five main mechanisms of action:
Inhibiting the virus’ ability to infect cells by transporting zinc across cellular membranes
Inhibiting replication of already infected cells
Reducing infected cells’ resistance to treatment with antiviral medication
Inhibiting platelet aggregation — and many COVID-19 patients suffer abnormal blood clotting
Promoting SIRT2, thereby inhibiting the NLRP3 inflammasome assembly involved with COVID-19 infection
Similarly, vitamin C at extremely high doses also acts as an
antiviral drug, effectively inactivating viruses. During the 2003 SARS
pandemic, a Finnish researcher called6
for an investigation into the use of vitamin C after research showed it
not only protected broiler chicks against avian coronavirus, but also
cut the duration and severity of common cold in humans and
significantly lowered susceptibility to pneumonia.
The MATH+ Protocol
While high-dose vitamin C is new for COVID-19 treatment, it’s been
used as a treatment for sepsis since about 2017. The vitamin C-based sepsis treatment
was developed by Dr. Paul Marik, a critical care doctor at Sentara
Norfolk General Hospital in East Virginia, which has since adopted it
as standard of care for sepsis.
In the interview above, Marik explains how the COVID-19 critical
care protocol grew out of his sepsis treatment, as he and other doctors
noticed there were many similarities between sepsis and severe
COVID-19 infection, in particular the out-of-control inflammatory
cascade.
To address the differences between the two conditions, a group of
doctors, including Marik, founded the Front Line COVID-19 Critical
Care Working Group7 (FLCCC), and began developing a modified protocol specifically for COVID-19.
The original protocol for COVID-19 is detailed in “COVID-19 Critical Care.” Known as the MATH+ protocol,8,9 it involves the use of three key medicines, all of which need to be started within six hours of hospital admission:
Intravenous methylprednisolone, to suppress the immune system and prevent organ damage from cytokine storms
Intravenous ascorbic acid (vitamin C), to control inflammation and prevent the development of leaky blood vessels in the lungs
Subcutaneous heparin (enoxaparin), to thin the blood and prevent blood clots
MATH+ Prophylactic and At-Home Treatment Protocol
The initial MATH+ protocol10 was released in April 2020. In early July and August, it was updated11,12
to include quercetin and a number of optional nutrients and drugs, not
only for critical care but also for prophylaxis and mild disease being
treated at home.
For prophylaxis, the FLCCC recommends:13
Vitamin C — 500 mg
Quercetin — 250 mg to 500 mg
Zinc — 75-100 mg/day (acetate, gluconate or picolinate). Zinc
lozenges are preferred. After one month, reduce the dose to 30 mg to 50
mg per day
Melatonin (slow release) — Begin with 0.3 mg and increase as tolerated to 2 mg at night
Vitamin D3 — 1,000 to 4,000 IUs per day
The at-home treatment for mildly symptomatic patients is very
similar, but adds several optional drugs, including aspirin (ASA),
famotidine (an antacid), ivermectin (a heartworm medication that has
been shown to inhibit SARS-CoV-2 replication in vitro14). (For dosages, see the Critical Care Management Protocol15 summary, available on the Easter Virginia Medical School’s site.)
They also recommend monitoring your oxygen saturation with a pulse
oximeter and to go to the hospital if you get below 94%. The medical
evidence to support each drug and nutrient can be found under “Medical
Evidence”16 on the FLCCC’s website.
MATH+ Critical Care In-Hospital Protocol
In July, the in-hospital protocol was revised17
again to include thiamine (which is also a key ingredient in Marik’s
sepsis protocol). As of the last revision, the in-hospital MATH+
protocol18 calls for:
IV methylprednisone
High-dose ascorbic acid (vitamin C)
Thiamine
Heparin
Optional: melatonin, zinc, vitamin D3, atorvastatin, famotidine and magnesium
According to the FLCCC, “By initiating the protocol soon after a
patient meets criteria for oxygen supplementation, the need for
mechanical ventilators and ICU beds will decrease dramatically.” While
heparin is an important part of the protocol due to the clotting
complications in the microvasculature of the lung, it is likely that
N-acetyl cysteine (NAC) is likely a far better choice as it is far safer
and likely as effective.
The Two Phases of Disease Require Different Treatments
This is a key point: There are two distinct phases or stages of
COVID-19 — the viral replication stage and the immune dysfunction stage
— and the treatment must be appropriate for the stage you’re in.
Equally crucial is starting aggressive treatment as early as possible.
The graphic below details the two stages of disease, and the FLCCC’s
suggested treatment focus for each.
Peak viral replication takes place at the earliest signs of
symptoms, which include cold/flu-like symptoms, loss of taste and
smell, myalgia (muscle pain) and general malaise.
From the time of symptom onset to the time that immune dysregulation
starts to set in (accompanied by worsening symptoms) is about five or
six days. During this time, you need to aggressively treat, whether
you’re at home (see the at-home treatment for symptomatic patients) or
in the hospital.
The key remedies in this phase are antivirals (which is what vitamin
C, quercetin and zinc are). Anti-inflammatories should be avoided in
this phase, Marik warns. Again, if treating at home, be sure to monitor
your oxygen saturation with a pulse oximeter. If your oxygen drops to
94% or below when sitting or walking, it’s time to go to the hospital.
If your immune system is unable to successfully combat the virus,
then five to six days after first symptoms, early pulmonary dysfunction
can set in. At this point, anti-inflammatories — i.e., corticosteroids
— and immune suppressive therapeutics are required.
Viral Load Declines as Inflammation Rises
Another important concept explained by Marik in the featured
interview is that the inflammatory response rises as the viral load
decreases. They do not rise together.
“So, it’s really not the virus that is causing cytopathic effects,”
he says. By the time you enter the pulmonary phase of the disease, your
viral load has actually significantly decreased, but for some reason
the inflammatory response then starts to run amok.
Your oxygen saturation is “the key indicator of pulmonary
involvement,” Marik says. Once your oxygen saturation starts to
decline, you are entering the early pulmonary phase where inflammation
is rapidly increasing.
This is why it’s so important to make sure you’re measuring your
oxygen saturation. Do not try to treat at home if your oxygen is
dropping. Go to the hospital. Again, early treatment is crucial.
Hopefully, your doctor will be willing to implement the MATH+ protocol.
Corticosteroids Are a Crucial Component
In a short essay19
co-written by the entire FLCCC team, they express their conviction that
the MATH+ protocol is one of the best, most effective, critical care
protocols for COVID-19 to date.
“Months ago, early on in COVID19, the FLCCC created the MATH+
protocol based on our physicians’ insights into COVID19 as a
steroid-responsive disease.
This treatment recommendation went against all the major
national and international health care societies that had
misinterpreted the medical literature, a body of published evidence
which, upon careful and deep review, actually supported the use of
corticosteroids in prior pandemics …
Thousands of patients who became critically ill with Covid19 and
who were suffering from massive inflammation may have been saved if
this safe and powerful anti-inflammatory medicine had been provided.”
The essay20 stresses the importance of corticosteroids in the treatment of COVID-19, and cites results from the RECOVERY trial,21,22,23
a large, randomized controlled COVID-19 study by the University of
Oxford, that validates their recommendation to use corticosteroids as
soon as the patient is hospitalized.
In that study, the corticosteroid dexamethasone improved survival by
one-third in ventilated patients and one-fifth in those requiring
oxygen. However, the FLCCC believes another type of
corticosteroid, methylprednisolone, is a better, more effective, choice.
First, because it reaches higher concentrations in lung tissue, and
secondly, because it most closely matches the inflammatory gene
activation patterns induced by SARS-CoV-2. They also believe the
dexamethasone dose used in the RECOVERY trial was too low, especially
for severe cases.
“In the hospitals of two of our FLCCC physicians — each having
treated over 100 hospitalized patients with MATH+ often early on in the
hospitalization, the hospital mortality rate to date is 7% in one
hospital (Dr. Paul Marik, Norfolk, Va.) and less than 1% in the other
(Dr. Joseph Varon, Houston, Texas),” the essay states.24
Vitamin C and Quercetin Work Synergistically
June 19, 2020, Marik published the paper,25
“Quercetin and Vitamin C: An Experimental, Synergistic Therapy for the
Prevention and Treatment of SARS-CoV-2 Related Disease (COVID-19)” in
the journal Frontiers in Immunology, which notes:
“Ascorbic acid is a crucial vitamin necessary for the correct
functioning of the immune system. It plays a role in stress response
and has shown promising results when administered to the critically
ill. Quercetin is a well-known flavonoid whose antiviral properties
have been investigated in numerous studies.
There is evidence that vitamin C and quercetin co-administration
exerts a synergistic antiviral action due to overlapping antiviral and
immunomodulatory properties and the capacity of ascorbate to recycle
quercetin, increasing its efficacy.
Safe, cheap interventions which have a sound biological
rationale should be prioritized for experimental use in the current
context of a global health pandemic.”
The paper presents evidence for the use of vitamin C and quercetin
— based on their biological actions and pharmacokinetics profiles —
both as prophylaxis in high-risk populations, and as an adjunct to
drugs such as Remdesivir or convalescent plasma in the treatment of
hospitalized COVID-19 patients.
Post-COVID Syndrome
In the interview, Marik also addresses the issue of “post-COVID
syndrome,” which he says is very similar to that of post-sepsis
syndrome. In some cases, COVID-19 patients have recovered from the
infection, only to die due to pulmonary embolism (blood clots in the
lungs) or other organ dysfunction.
Marik suspects this is because the inflammatory response is still
overactive. Many sepsis patients will have very high cytokine levels
even a year after their recovery. He believes steroids are one key to
downregulating the inflammatory response, which would prevent this
problem.
A good way to screen for this, Marik says, is to measure CRP, which
appear to be a good marker for ongoing inflammation. If CRP is high
after recovering from COVID-19, Marik suggests doing a short course of
corticosteroids to downregulate the inflammatory response. Aspirin may
also be helpful if D-dimer is high. These should be used under medical
supervision.
I believe this information needs to be shared far and wide, if we
are to prevent more people from dying unnecessarily. More and more, as
doctors are starting to speak openly about their clinical findings, we
see there are quite a few different ways to tackle this illness without
novel antivirals or vaccines, using older, inexpensive and readily
available medications and nutrients that are already known to be safe.
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