A glutathione
deficiency may be at the root of severe illness, as it leads to
significant oxidative stress, lung inflammation and multiorgan failure
with COVID
One scientist
linked glutathione deficiency with many of the comorbid conditions that
raise COVID-19 severity, including age, diabetes, gender and smoking
The researcher
also found data indicating that glutathione deficiency can impact your
ability to synthesize vitamin D, another risk factor for severe disease
NAC
supplementation, foods rich in glutathione precursors, aerobic exercise
and strength training can help support healthy levels
Coronaviruses were identified in the
mid-1960s and so named for the crown-like spikes on the surface of the
cell. Until the first SARS-CoV arrived in 2003, there were four common
coronaviruses.1 The CDC’s list of symptoms for these viruses shows that they are the same as those of the common cold.2 They include a runny nose, sore throat, headache, fever and cough.
However, from what scientists have discovered since the start of the
global pandemic, the symptoms and long-term effects are far different
for SARS-CoV-2. Initial symptoms include fever, cough, shortness of
breath, fatigue and loss of taste or smell.3 However, unlike a natural coronavirus, the additional complications can affect the cardiovascular system, kidney, liver and lungs.4
One of the identified underlying dysfunctions that trigger shortness
of breath and severe lung complications is hypercoagulability. In one
study, patients who were admitted to Padova University Hospital in Italy
for acute respiratory failure showed "markedly hypercoagulable
thromboelastometry profiles." The researchers said:5
"In conclusion, COVID-19 patients with acute respiratory failure
present a severe hypercoagulability rather than consumptive
coagulopathy. Fibrin formation and polymerization may predispose to
thrombosis and correlate with a worse outcome."
Clot formations throughout the body may be associated with other
complications arising after the illness has resolved. It appears that
the difference between people who have a mild or severe illness may be
related to the body’s ability to reduce the hypercoagulability and the
hyperimmune response that leads to a cytokine storm.
How Glutathione Works — A ‘Master Antioxidant?’
An antioxidant is a molecule that keeps other molecules from
oxidizing. Glutathione is a powerful antioxidant that may play a
significant role in the COVID-19 illness process. There are 20 amino
acids that can bind together in different formations to create a protein
molecule.6
However, glutathione is a tripeptide, which means there are only
three amino acids that line up to form a glutathione molecule. These are
cystine, glycine and glutamate. Together they help use and recycle
other antioxidants, such as vitamin C and CoQ10.7,8
This means your body uses glutathione to increase the effectiveness
of these antioxidants and it helps to recycle the molecules. Without
glutathione, the antioxidant capacity is significantly reduced. This
function may be what earned glutathione the nickname “master
antioxidant.”9 N-acetylcysteine (NAC) plays a role as a precursor to glutathione.10
Clinical evidence has also demonstrated the effects NAC has,
independent of its role with glutathione, including a thrombolytic
effect. It also improves oxidative stress and the inflammatory response.11,12,13,14
In late March 2020, one medical student put this theory to the test
when his mother, 48-year-old Josephine Bruzzese, was diagnosed with
pneumonia at NYU Langone Hospital-Brooklyn. Without an available
COVID-19 test, they sent her home as a suspected case. She was
prescribed hydroxychloroquine and azithromycin, which helped improve
some symptoms, but not her breathing.
When she was unable to stand, and had severe respiratory problems,15
her son contacted Dr. Richard Horowitz, a specialist who was treating
his sister for Lyme disease, who suggested using glutathione to help
reduce the inflammation and protect Bruzzese's lung tissue. The results
were dramatic.
Within one hour after receiving a 2,000 mg dose of glutathione, her
breathing was better, and she could stand. She continued to take
glutathione for five days and has not had a relapse. Speaking to a
reporter from the New York Post, Horowitz shared that he is working to
design an extensive clinical trial to prove the effectiveness of what he
calls "an easy treatment that is not expensive."
May 5, 2020, Memorial Sloan Kettering Cancer Center posted a trial to
Clinicaltrials.gov announcing a study involving the use of NAC in
patients with COVID-19. In this first-of-its-kind research, the study
team plans to enroll patients with severe disease: One group in the
study will receive 6 grams of NAC intravenously each day in addition to
other treatments.16
Scientists Propose Deficiency Is Linked to Severe COVID-19
About the same time the study was announced by Memorial Sloan
Kettering, a Russian scientist published papers proposing that
glutathione plays a crucial role in a person's ability to respond to a
COVID-19 infection and the resulting severity of disease.17,18,19 In this short video, Dr. Roger Seheult explains the science.
Additionally, Dr. Alexey Polonikov, from Kursk State Medical
University, theorizes glutathione can be used as a preventive against,
and treatment of, the illness. Polonikov studies human molecular
genetics and oxidative stress.20
Based on the exhaustive literature analysis he conducted, he later
said he believes glutathione deficiency is a plausible reason for
serious illness with COVID-19:21
“(1) oxidative stress contributes to hyper-inflammation of the
lung leading to adverse disease outcomes such as acute respiratory
distress syndrome, multiorgan failure and death;
(2) poor antioxidant defense due to endogenous glutathione
deficiency as a result of decreased biosynthesis and/or increased
depletion of GSH is the most probable cause of increased oxidative
damage of the lung, regardless which of the factors aging, chronic
disease comorbidity, smoking or some others were responsible for this
deficit.”
As Polonikov writes22 and Seheult describes in the video, oxidative damage
from reactive oxygen species (ROS) plays a significant role in severe
disease with COVID-19. In another video, Seheult explains how COVID-19
sets the stage for significantly increasing oxidative stress by
increasing superoxide, a damaging ROS.23
Importantly, this raises superoxide in people who start with high
levels due to chronic diseases such as heart disease, diabetes and high
blood pressure. As the virus uses the ACE2 enzyme, it generates
angiotensin II, which in turn generates more superoxide.
The virus also attracts a type of neutrophil (polymorphonuclear
leukocytes) that can also raise the production of superoxide. The
superoxide then produces other hydroxyl radicals, including hydrogen
peroxide (H2O2).
These ROSs, which cause cellular damage, can be reduced with
glutathione peroxidase as it oxidizes glutathione in the process of
reducing H2O2 to water. As you can see, a deficiency of glutathione
would create a build-up for ROS as Polonikov describes.
Comorbid Risk Factors Linked to Glutathione Deficiency
Antioxidant defense against ROS damage is crucial for whole body
homeostasis. Polonikov believes a higher rate of severe illness from the
virus in older adults and those with comorbidities suggests there are
related biological processes that make these specific individuals more
sensitive. He writes:24
“Specifically, impaired redox homeostasis and associated
oxidative stress appear to be important biological processes that may
account for increased individual susceptibility to diverse environmental
insults.”
In one evaluation of COVID-19 patients from six hospitals in Atlanta,
researchers found independent factors that raised the risk of
hospitalization. These included smoking, having Type 2 diabetes, being
male, being Black, being of advanced age and being obese.25 Polonikov found evidence that a glutathione deficiency may be implicated in these comorbidities.
In his paper he identifies the progressive reduction in endogenous
glutathione with aging. This, he believes, makes “the elderly more
susceptible to oxidative damage caused by different environmental
factors compared to younger individuals.”26 He points out that deficiencies in endogenous glutathione are also found in people who have other comorbid conditions.
He proposes these decreased levels with chronic disease
could begin a shift toward oxidative stress and exacerbate pulmonary
inflammation, ultimately leading “to acute respiratory distress syndrome
(ARDS), multiorgan failure and death.”27 Some men and some smokers also have lower levels of glutathione, which increases their risk.
In another ongoing study on the genetics of redox homeostasis and
Type 2 diabetes, four patients from the control group contracted
COVID-19. Blood samples were collected and used to measure ROS and
glutathione levels.28
All four were female nonsmokers without chronic disease who had a
confirmed positive PCR test. In cases of individuals who recovered
quickly, the ROS-to-glutathione ratio was 2.075-to-0.712 or less.
In patients with more significant disease, the ratio was
3.677-to-0.531 in one patient and as high as 2.73-to-0.079 in the
second. In the first patient with significant disease the ratio was more
than double that in patients who recovered quickly. In the second
patient the ratio was more than 11 times greater.
Glutathione and Vitamin D Relationship
In terms of vitamin D, Polonikov proposes the relationship between
vitamin D and severe disease may have more to do with a glutathione
deficiency. He points to several studies that correlate glutathione
levels with vitamin D29,30
and another in which scientists found that lower levels of l-cysteine, a
glutathione precursor, correlated with lower vitamin D levels in people
with Type 2 diabetes.31
In a recent animal study researchers also looked at whether
glutathione deficiency could induce changes that impaired the metabolism
of vitamin D.32
They found the deficiency could alter the biosynthesis and explained
the mechanism for vitamin D deficiency that occurs with a glutathione
deficiency.
The researchers suggest there's a potential benefit to supplementing with glutathione in order to reduce vitamin D deficiency.
Polonikov writes that this study supplies information on the importance
glutathione plays in the control of endogenous vitamin D biosynthesis
and demonstrates the benefits of treatment in reducing vitamin D
deficiency.
I believe both nutrients are vital for protection against severe
disease. While a glutathione deficiency may impact your ability to
synthesize vitamin D, this is applicable only when you have enough sun
exposure or supplements to raise your vitamin D level.
However, we know it is difficult to get enough sun in the Northern
Hemisphere, especially during the winter months. Additionally, most
people use copious amounts of sunscreen or avoid the sun altogether,
which can make the deficiency problem worse.
Strategies to Support Optimal Glutathione Levels
Your glutathione levels can be optimized using food, supplements and
exercise. Polonikov believes that NAC taken orally may be a preventive
strategy to help support your levels. In his paper he concluded:33
“Therefore, oral administration of N-acetylcysteine as a
preventive measure against viral infections, as well as intravenous
injection of NAC or reduced glutathione (GSH is highly bioavailable) in
patients with serious illness may be effective options against novel
coronavirus SARS-CoV-2 infection."
As he discusses in the video, Seheult believes there is more to the damage by COVID-19 than oxidative stress.34
He points out that the clots removed from patients with confirmed COVID
are rich with platelets, indicating another mechanism involving
disulfide bonds. He goes on to explain:35
“And, as we've already talked about N-acetylcysteine and reduced
glutathione will break these disulfide bonds and cause them to lyse and
potentially relieve the obstruction and the hypoxemia with COVID-19.
Again, this is all a hypothesis, but it looks as though it's fitting
together."
Foods that have had a positive impact on glutathione production
include cruciferous vegetables such as broccoli, green tea, curcumin,
rosemary and milk thistle.36 Getting quality sleep may also help.37,38
Different types of exercise
can influence your levels. In one study researchers enrolled 80 healthy
but sedentary volunteers to measure the type of exercise that may have
the greatest effect.39 They found that aerobic training in combination with circuit weight training showed the greatest benefit.
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