COVID-19 has hit the world by storm, but only some parts of the world. In particular, as of Oct 22, 2020, the top 23 countries ranked by death rate per 100,000 population were all in either the Americas or Europe [1]. The mortality rate is strikingly different from one country to another. For example, Taiwan and Vietnam have had only 0.03 and 0.04 deaths per 100,000 respectively, whereas the 23 top countries all have a death rate greater than 38 per 100,000 – a factor of 1000 difference or three orders of magnitude.

I have previously proposed that an overlooked factor in COVID-19 mortality statistics is the impact of chronic glyphosate exposure. Glyphosate is the active ingredient in the pervasive herbicide Roundup, and it is very commonly used to control weeds in large industrialized farms or as a desiccant just before harvest. It has become clear that a number of comorbidities such as diabetes, hypertension, and obesity are risk factors for a severe case of COVID-19. In the United States, these chronic diseases are rising in the population exactly in step with the rise in the use of glyphosate on core crops [2]. I believe that glyphosate is the primary factor causing an epidemic in these diseases.

Most concerning to me is the possibility that glyphosate is getting released into the atmosphere as a consequence of the biofuel industry. The United States, Brazil, Argentina, and most European countries have all played a leadership role in developing technology to enable waste from the food industry to be converted into useful fuel. Sources for such fuel include the residue of crops following the harvest, manure and by-products of the meat-processing industry, waste oil from restaurants, and wood scraps from the paper-manufacturing industry. All of these can be expected to be contaminated with glyphosate. Cities where biodiesel, biofuel for heating oil, aviation biofuel, bioethanol and/or biogas are being rapidly ramped up, are likely to be badly impacted by COVID-19, because glyphosate exposure through breathing disrupts immune function in the lungs, interfering with the ability to rapidly clear the SARS CoV-2 virus [3]. I wrote about this in an earlier article in Masters of Health [4].

I believe this moment in history marks the beginning of a new era in our understanding of human metabolism and human physiology. COVID-19 is a fascinating and complex disease, but there is an army of researchers intent on figuring out what is happening in severe cases, and collectively they are making important discoveries. Here, I will develop the argument that deuterium is central to the disease process. As you will see, I believe that proper deuterium fractionation is crucial for metabolism to work properly in the mitochondria. I am coming to the realization that the water accumulating in the lungs - a common feature of COVID-19 – is actively participating in a plan to restore mitochondrial health to the immune cells and beyond. This may even be a general feature of edema anywhere in the body.

This article will take you through a whirlwind tour of several factors in health and disease, and space does not permit more than a brief introduction to each of them. If you want to explore more deeply, a good place to start is to look up any of the papers referenced at the end.

1 Deuterium

I first became aware of the role deuterium plays in health in December 2019, when Prof. László Boros reached out to me and explained the remarkably damaging effects that deuterium has on mitochondria [5]. Deuterium is the heavy isotope of hydrogen. Hydrogen is the smallest atom, with just one proton and one electron. Deuterium is the same, except that it also has an extra neutron. This makes it about twice as heavy as hydrogen, which gives it distinct physical and chemical properties. Deuterium is pervasive in nature - it is present at 155 parts per million in seawater. Mitochondria are small organelles contained in large numbers in most eukaryotic cells, and they are responsible for producing ATP (adenosine triphosphate), the energy currency of the cells. When they make ATP, they also combine protons with oxygen to make water, in the famous oxidative phosphorylation reaction that takes place across a mitochondrial membrane.

Systemic mitochondrial deterioration is a primary marker of the aging process [6]. Mitochondrial dysfunction has been linked to many neurological, metabolic, and oncological diseases, as aged mitochondria spew out more tissue-damaging reactive oxygen species (ROS) and produce ATP less efficiently. Mitochondria depend upon a “proton motive force” to produce ATP, which involves pumping huge numbers of protons across a membrane through the ATPase pump. Deuterons, being larger and heavier, disrupt the smooth flow and decrease the efficiency of the pump, much like putting sugar in the gas tank.

Biological organisms have developed a remarkable and sophisticated system for making sure that the protons in the mitochondria are not deuterons. There are two main parts to their strategy - trapping deuterium in gelled water and selecting for hydrogen over deuterium in catalytic reactions involved in supplying protons to the pump.

Most of the water in the body is trapped in a gel that is maintained by a “glycocalyx,” through the synthesis of large complex amino-sugar chains called glycosaminoglycans (GAGs). Crucial to maintenance of the gel are sulfate anions that are attached to these GAGs. The glycocalyx lines all the blood vessels of the body, and as described eloquently by Gerry Pollack in his book, “Cells, Gels and the Engines of Life,” the gel pushes protons out and maintains a negative charge within its interior, essentially creating a battery that can be used as an energy source. Because deuterons are heavier and they form stronger covalent bonds, they tend to be left behind in the gel [7]. I proposed in a TEDx Talk that these protons are ushered into the cell along cytoskeletal channels and delivered to the mitochondrial intermembrane space to be used in ATP synthesis [8].

The second way that the mitochondria assure low deuterium contamination in their ATPase pumps is through a set of specialized enzymes that extract protons from organic molecules and deliver them to the intermembrane space. These enzymes take advantage of a unique skill of protons called proton tunneling, to carry out the reaction. Deuterons are very poor tunnelers, so they get left behind. A large class of enzymes called flavoproteins are very good at exploiting proton tunneling to select hydrogen over deuterium, and they play an essential role in keeping deuterium out of the mitochondrial water being produced by the ATPase pumps.

2 Glyphosate and Deuterium

I have argued in multiple published papers that a unique aspect of glyphosate’s insidious cumulative toxicity is its ability to get inserted into proteins by mistake in place of the coding amino acid glycine [9, 10]. Glycine is the smallest amino acid – one of the twenty or so building blocks of proteins according to the DNA code. Glyphosate is a complete glycine molecule, except that it has an extra methylphosphonate unit attached to its nitrogen atom. The enzyme that glyphosate famously disrupts in the shikimate pathway in plants has a glycine residue at the site where it binds to a phosphate anion in its substrate. Species that have a mutated form of the enzyme, with alanine replacing this glycine residue, are completely insensitive to glyphosate [11]. Once there is no glycine, there is no chance to substitute and disrupt the protein.

The flavoproteins that I mentioned above bind to phosphate-containing small molecules called flavins, and this binding is essential for them to be able to carry out proton tunneling. The site where they bind flavins contains a so-called P-loop “GxxGxG” motif - a sequence of six amino acids where there are three glycine residues and three other amino acids that could be anything (x = wildcard). Thus, these enzymes have three glycine residues that are highly susceptible to glyphosate substitution, because glyphosate can settle its methylphosphonate attachment into the spot normally reserved for the phosphate unit in the substrate. Glyphosate substitution will block flavin binding and destroy the enzyme’s ability to transfer protons.

Sulfate supplies can also be expected to be depleted by glyphosate, and this will disrupt the ability of the organism to maintain adequate amounts of gelled water. I have previously discussed multiple ways in which glyphosate would disrupt sulfate synthesis, sulfate transport, and sulfate transfer from one molecule to another [9]. An enzyme called PAPS (phosphoadenosine phosphosulfate) synthase combines a sulfate anion with ATP to produce the activated form of sulfate that can then be attached to the glycocalyx. PAPS synthase has a GxxGxG motif at the ATP binding site, and is therefore vulnerable to glyphosate’s mischief.

3 Bradykinin Storm

Although COVID-19 is a new disease, there have already been hundreds of papers published describing the unique aspects of this disease. One of the most interesting ones to me is a paper that used computational techniques to analyze “gene expression data from cells in bronchoalveolar lavage fluid (BALF) from COVID-19 patients that were used to sequence the virus.” [12] Their technique allowed them to determine which proteins were upregulated (overexpressed) in the alveoli in the lungs of the infected patients. Bronchoalveolar lavage is a medical procedure in which a small amount of fluid (BALF) is squirted into the lung via a bronchoscope and then recollected for analysis.

They found that a protein called bradykinin was produced in large amounts in the infected lungs. Bradykinin is a powerful signaling molecule which causes a drop in blood pressure and induces leakages in the blood vessels that allow both immune cells and fluid to escape from the blood and enter the interstitial spaces. In addition, they found overproduction of hyaluronic acid in the lung alveoli. Hyaluronic acid is a very long amino-sugar molecule to which heparan sulfate chains can attach to form gelled water. Through osmosis, hyaluronic acid will attract and immobilize the fluid escaping from the blood, and in this way induces pulmonary edema, a characteristic feature of ARDS (acute respiratory distress syndrome) [13]. This can explain the sensation of drowning that COVID-19 patients have experienced. By trapping gelled water, the hyaluronic acid creates a negatively charged gel that releases protons into the interstitial spaces, to fuel the mitochondria of cells that are there.

4 Viral Lipid Envelope and Lipoxygenase

There is a class of enzymes called lipoxygenases that have an extraordinary ability to favor hydrogen over deuterium, and that produce therefore severely deuterium depleted water (DDW) by extracting hydrogen from fatty acids and combining it with oxygen [14]. These enzymes depend on iron as a catalyst, but they are not flavoproteins, so they are not susceptible to disruption by glyphosate in the way that flavoproteins are. Lipoxygenase is upregulated during inflammatory conditions, and it oxidizes the lipids in the membranes of cells and in the LDL particles in the blood, modifying the lipids into molecules called leukotrienes that have powerful bioactive signaling capabilities. The cascade response to these leukotrienes leads to vascular leaks, edema and the accumulation of immune cells at the inflammatory site [15].

Remarkably, it has been discovered that the SARS CoV-2 virus protein coat contains three pockets within its contour shape that perfectly and specifically fit a very common fatty acid called linoleic acid [16]. This is the most common fatty acid in the membranes of human cells, and it is surmised that the virus picks up multiple molecules of linoleic acid as it exits the human host cell, surrounding itself with a lipid envelope. Since the immune cells respond to the virus by inducing an inflammatory response, and an inflammatory response induces lipoxygenase, it can be predicted that the linoleic acid trapped in the membranes of the viruses will be metabolized by lipoxygenase to produce leukotrienes, while also further supplying DDW to the surrounding fluids. This sets up a perfect situation for macrophages (“big eaters” – immune cells that specialize in clearing viruses) to congregate and partake of the sweet nectar that is being created through the immune response to the virus.

5 Mitochondrial Rejuvenation

It has only recently become known to researchers that cells have a remarkable ability to share their mitochondria among one another, and that this practice can lead to a healing process for sick immune cells. We can now recognize that an acute reaction to SARS CoV-2 results in an intense inflammatory response that sets in motion a dramatic sequence of events, possibly with the ultimate magnanimous goal of energizing the macrophages so that they can effectively clear the virus. Such a response only happens when the immune cells are impaired due to prior toxic exposure, and I believe glyphosate is a major culprit. If the immune cells were healthy, they would have easily cleared the virus without overt symptoms of disease.

Inflammation induces the extraction of protons from the fatty acids in the viral envelope to produce DDW, while at the same time triggering overproduction of hyaluronic acid, which can trap deuterium-rich water in a gel, accumulating in the alveoli and further depleting deuterium in the remaining fluid interstitial water. The leaky blood barriers that are also induced allow not only macrophages but also mesenchymal stem cells emerging from the bone marrow to congregate in the fluids in the lung interstitial spaces that have been scrubbed of their deuterium. The mesenchymal stem cells gift their mitochondria to the macrophages by releasing them into tunneling nanotubes that stretch across from a source cell to a recipient cell [17]. It is plausible that they can pick up some of that DDW along the way. The mitochondria can also be released directly into the medium and swept up into a vacuole, formed in a recipient macrophage, after they have restored DDW in their intermembrane space. The vacuole itself can be directly supplying a large quantity of trapped DDW to the cell that internalizes it.

Besides mesenchymal stem cells, platelets are also a fantastic source of fresh mitochondria for the macrophages. Platelets are tiny cell fragments with no nucleus that each contain a handful of mitochondria. Under stressful conditions, so-called “activated” platelets release their mitochondria into the medium, either as isolated mitochondria or packaged up inside lipid particles called exosomes [18]. The macrophages take up these mitochondria, most likely after they have been re-enforced with deuterium depleted water. It is even conceivable to me that a primary function of platelets is to serve as a reserve supply of healthy mitochondria for the immune cells.

Thus, the virus has orchestrated a fantastic repair mechanism which then empowers the macrophages to be able to clear the virus, because they have now been endowed with an adequate supply of healthy mitochondria. This makes an argument for a very different viewpoint on the role of viruses in health and disease. The viruses appear to be collaborating with the host cells in an intricate dance that ultimately results in healing, unless there are too many toxic interferences that derail the plan.

6 Drastic Final Measures

In some patients, all of the above efforts are not good enough, likely because their macrophages’ mitochondria are severely impaired due to chronic exposure to glyphosate and/or other toxic chemicals. When this happens, a systemic response ensues, involving all the blood vessels throughout the body. An enzyme called heme oxygenase is massively produced in response to sustained low oxygen availability, and it breaks down the heme that is present in large amounts in the red blood cells, converting it to biliverdin. Biliverdin in turn gets converted to bilirubin, an outstanding antioxidant that can protect from oxidative damage due to peroxynitrite and peroxyl radicals [19]. But, for every molecule of biliverdin that is produced, three molecules of deuterium depleted water are also produced. It has been shown that generally heme oxygenase is a healthy and welcomed response to inflammation, which eventually tames the inflammation and resolves the disease process [20].

However, glyphosate can interfere with this process as well, by substituting for a critical glycine residue in heme oxygenase. Mutations in this glycine residue have been shown to convert heme oxygenase into a rogue version of itself that not only can’t break down heme (and therefore can’t produce DDW), but also releases highly inflammatory ferryl iron (Fe+4) from the heme [21, 22]. This has the opposite effect of what is expected, and it can result in a hopeless positive feedback loop and a runaway inflammatory cascade. Ultimately, massive blood clots form throughout the capillaries and the patient dies of disseminated intravascular coagulation or of multiple organ failure. I described this effect in a recent previous article in Masters of Health [23].

7 Conclusion

For all its down sides, COVID-19 has a silver lining, which is the opportunity to learn more about human biology through careful study of patients who become seriously ill, ending up in the ICU, or in the morgue. Collectively, the many papers on the COVID-19 disease process reveal a fantastic mechanism by which a serious mitochondrial disorder in the immune cells can be efficiently repaired, with the help of SARS CoV-2. It necessitates uncomfortable symptoms such as a sense that you are drowning due to the accumulation of deuterium depleted water in the lungs. But this water enables the macrophages to repair their mitochondria, which then empowers them to clear the virus, metabolizing the viral components into useful raw materials. Ultimately, it strengthens the host’s immune system.

But this may not be enough for patients who have been more severely compromised by glyphosate and other environmental toxins, and these unfortunate individuals progress into a more severe stage where platelet involvement can lead to massive production of blood clots throughout the vasculature, with potentially life-threatening consequences. It may be that the very best way to protect yourself from COVID-19 is to consume a 100% certified organic whole foods diet.