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COVID-19: Clot and Stroke Prevention?

Mounting evidence that COVID-19 manifests as a vascular disease has been recently highlighted in the news. New treatment parameters are looking at the use of blood-thinners as a way of preventing strokes and thrombotic events that threaten the lives of those infected with the disease. (1)

The conversation needs to start with a reminder: blood thinners are serious stuff. No one should ever take medication that is not prescribed for them, or take massive amounts of natural supplements in an attempt to treat or prevent serious illness. If any symptoms of COVID-19 develop, including cardiovascular symptoms, seek professional medical help immediately.

Besides safety concerns of self-medication, the fact remains that scientists are still looking for answers. Early perspectives on the use of blood thinners for prevention are cloudy, and they may not be enough to stop the worst outcomes.

At this point, it makes sense to ask WHY this is happening… Why are some patients developing clotting disorders? And what can we do about it?

To answer this question, let’s turn to a highly respected source of current information on COVID-19, Roger Seheult, MD, pulmonologist and co-founder of MedCram (2).

You have likely heard by now that SARS-CoV-2 invades the human body by binding with the ACE2 receptors, found notably in the lungs. Because the virus predominantly gains access to its host through the lungs, causing a wide range of respiratory symptoms, a lot of focus for care has been geared toward limiting respiratory distress.

It turns out that the specialized lining of our blood vessels, the endothelium, also has ACE2 receptors. By invading the lungs, the SARS-CoV-2 virus can further invade the vascular system, disabling the ACE2 receptor, and so indirectly stimulating vasoconstriction/high blood pressure and inflammation of the inner lining of the blood vessels (the endothelium). 

Long story short? Inflammatory chemicals secreted by the endothelium lead to increased clotting factors and thrombotic events. Possibly, this is what is most deadly about COVID-19… and perhaps, treatments that regulate endothelial function and address endothelial inflammation, can lead to better outcomes.

If you want to dig a little deeper and understand the physiology and biochemistry involved, we need to take a look at the production of “reactive oxygen species” (ROS) within the cells. 

ROS destroys things. White blood cells, neutrophils particularly, use ROS to help the body eliminate pathogens, including coronavirus. 

That’s a good thing. 

An overabundance of ROS, however, causes damage to our own cells, and over time leads to chronic diseases, especially vascular disease, like atherosclerosis. 

Many physiological processes in the body generate ROS, even the production of energy by the cell (3), which gives off byproducts that can be damaging:

  • Superoxide (SO)
  • Hydrogen peroxide (H₂O₂) 
  • Hydroxyl radical (HO•)

Fortunately, a healthy system is equipped with its own antioxidant system to quell the inflammatory nature of these chemicals, and keep cell injury to a minimum. These antioxidants include:

  • Superoxide dismutase (SOD)
  • Catalase 
  • Glutathione peroxidase (GSHPX)

These antioxidants, manufactured within our magnificent bodies, do the handy job of inactivating ROS, turning them into water.

If our supply of antioxidants runs low, inflammatory levels rise and trouble ensues. Interestingly, if oxygen levels are low, as happens in respiratory disease, we also have a buildup of ROS, adding more stress on the system.  

The lining of our blood vessels has a rich, dynamic response to a myriad of information that travels through the blood stream. Regulation of blood pressure, by sending signals to vessel smooth muscle to contract or relax, is just one of many functions of the endothelium. 

The endothelium also plays a role in the regulation of clotting factors. ROS and inflammatory cytokines disrupt the endothelium and leads to the activation of clotting factors by a protein called “Von Willebrand Factor” (VWF). Before your eyes roll back in your head ?, take note that elevated serum levels of VWF are a hallmark of acute and chronic infection, and also signals endothelial dysfunction. 

High levels of VWF in the bloodstream predicts an unfavorable disease outcome marked by prothrombic complications (clots), organ failure, and death. Some patients who are very sick with COVID-19 have elevated levels of VWF, and are following this pattern precisely.

The question comes to mind: is it useful to address the health of the endothelium, both before infection and/or during infection? Is it possible to quench vascular inflammation, inhibit levels of VWF, and so protect against dangerous clotting during COVID-19?

Answers to these questions are of course just hypothetical – we are still guessing at this game. Here are some thoughts, inspired by Dr. Seheult’s series and by Guido Masé’s online course, Natural Cardio Care.

Dr. Seheult does an amazing job of explaining the role of glutathione peroxidase (GSHPX), and the antioxidants mentioned above, in quelling ROS and protecting the endothelium (4). GSHPX transforms hydrogen peroxide into water. To do this little piece of magic, it relies on the help of “reduced” glutathione (GSH). “Reduced” simply means it has an electron to donate to the good cause of quelling an oxidant. Once GSH gives up its electron, it changes form and is now oxidized. To make itself useful again it needs to be “recycled” back into its reduced state.

Even though this is a page out of the dreaded chemistry book, this can be really helpful to understand from an herbal perspective, since several plants, such as milk thistle and gotu kola, have been shown to enhance glutathione recycling. Other nutrients play a supportive role in the activity of glutathione, including selenium and glutamine. Of particular interest, from the perspective of fighting the fight against COVID-19, is a very useful supplement called N-acetylcysteine or NAC.

NAC is an over the counter supplement, an amino acid precursor, that has also been used in hospital settings for acetaminophen (Tylenol) poisoning, and as a mucolytic (thins mucus).  It is a powerful antioxidant and a 2017 article in Cell Journal (5) does a thorough review of the utility of this impressive supplement. 

In its use against COVID-19, NAC has potential as an antioxidant, as a glutathione recycling agent, and as an anticoagulant (blood thinner). One study is currently underway investigating the benefits of NAC for COVID-19 patients, administering a whopping 6 grams intravenously to the seriously ill. (6)  A 2017 article in Circulation (7) demonstrated that NAC acts directly to disrupt VWF in mice, the pro-clotting factor that we are seeing elevated in COVID-19 patients. Best of all, in trial after trial, NAC has demonstrated an outstanding safety profile.

Since NAC also reduces endothelial stress by restoring depleted antioxidants, it might make sense to use it in a preventive protocol, in combination with plants that nourish and support healthy endothelial function, such as hawthorn berry, flower, and leaf (Crataegus spp.). It’s heartening to see how some of the common plants many of us are already using on a daily basis may be part of the key to moderating the outcomes of this disease that we are only beginning to understand.

Hypothetically, in summary:

  • SARS-CoV-2 sets off an inflammatory cascade by binding to the ACE2 receptors in the lungs and vascular system. This inflammation can trigger severe respiratory issues as well as disrupt the endothelial lining of our blood vessels, setting up the scenario leading to clot formation.
  • NAC supports recovery in several ways:
    • Aids in glutathione synthesis, since it is a building block of the molecule 
    • Assists in glutathione recycling by breaking the disulfide bonds of oxidized glutathione
    • Acts directly as an antioxidant and so reduces inflammation
    • Interferes with unhealthy clot formation by disrupting sulfur bonds in VWF

Remember, this is promising news, but still theoretical. There are many unknown parameters, including whether oral NAC is as effective as IV, but the preliminary research has grabbed this herbalist’s attention!

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