Cholesterol Sulfate and the Sulfur Cycle

It seems to me that now is a good time to recapitulate what I have learned about cholesterol sulfate in my studies over the past several months, summarizing its roles, according to my understanding, and explaining the resulting pathology that arises when levels are depleted. I’m going to make this blog post as short and succinct as possible, in the hopes that people who may be getting lost in the details of the biology will be able to follow these high level arguments presented, I hope, in plain English.

Back when people spent a significant amount of their time outdoors, and hadn’t heard of sunscreen, they got plenty of sun exposure to the skin, and this allowed the eNOS in cells close to the surface layer of the skin to produce sulfate from sulfide and attach it to cholesterol. Some of the cholesterol sulfate got released into the blood stream, probably getting picked up by HDL-A1, and some of it ended up in the outer layer of the skin, where it plays a very important role in barrier function (keeping the skin water-tight and keeping out pathogenic bacteria). eNOS normally produces cholesterol sulfate not only in cells in the epidermis but also in cells that roam the blood, like platelets and RBCs. All of these cells contain functioning eNOS, and all of them produce cholesterol sulfate, which I do not think is a coincidence.

Today, due to our dietary avoidance of foods high in cholesterol and sulfur, and due to our sun avoidance and liberal use of sunscreen, we don’t get enough cholesterol sulfate supply, and this has huge ramifications everywhere. It’s most obvious, in my opinion, in the autism epidemic. In addition to their cognitive and social issues, autistic children have several characteristics that can be directly explained by cholesterol sulfate deficiency, namely, eczema, asthma, digestive problems, and increased susceptibility to infection.

I think preeclampsia (toxemia), a condition that now affects 6-8% of American pregnancies, and is rapidly increasing, is due to an insufficient supply of cholesterol sulfate for the fetus. To start with, cholesterol sulfate plays an essential role in fertilization. Furthermore, I believe that the fetus gets its entire supply of both cholesterol and sulfate from the cholesterol sulfate molecule, which can penetrate the placental barrier, unlike cholesterol. It has been shown that cholesterol sulfate shows up in profuse amounts in the placental villi in the last trimester of pregnancy, the same time during which preeclampsia develops. Preeclampsia is a very strong risk factor for future autism in the fetus.

In looking at heart disease, I think atherosclerosis develops as an alternative method to produce cholesterol sulfate, since the normal method through sunlight exposure to the skin has failed. As I’ve discussed before, the macrophages take up cholesterol from LDL and hand it over to HDL-A1, and the platelets combine the cholesterol from HDL-A1 with sulfate derived from homocysteine thiolactone (a process which requires superoxide and therefore ROS – reactive oxygen species) to produce cholesterol sulfate and release it to the blood.

What does the cholesterol sulfate do that’s so important? It supplies both cholesterol and sulfate to all the tissues. I cannot think of a more important thing to do! Sulfate plays an important role in the glycocalyx, which is a thick layer of attached glycosaminoglycans that decorate the artery wall, in keeping the blood and its suspended contents from seeping out into the tissues. Sulfate, a kosmotrope, pairs with sodium, a chaotrope, in the blood stream to maintain the appropriate kosmotrope/chaotrope balance that keeps proteins (and cells!) from salting-out/salting-in. What this means in plain English is that sulfate is needed to stabilize the blood. It’s clear from the research literature that cholesterol sulfate hangs out in the outer membrane of red blood cells, and it plays an important role in protecting them from falling apart.

I believe that RBC’s hand off cholesterol sulfate to the tissues (especially the heart, skeletal muscles, and neurons) as they pass through the capillaries. I further believe that muscles and neurons are able to process glucose in the caveolae of their cell membranes, using ferrous sulfate as a catalyst to help in the reaction converting glucose to pyruvate. Hydrogen peroxide is also required, and insulin will not induce GLUT4 to go to the membrane unless hydrogen peroxide is present. The reduction of the sulfur in sulfate to sulfide is a decoy exploiting the reducing power of glucose, to protect the cell’s proteins from glycation damage. The sulfur is first attached to pyruvate to form 3-mercaptopyruvate, and is then released from the pyruvate and easily passed into the blood stream as hydrogen sulfide, a signaling gas that has all the good properties of nitric oxide but none of the bad properties. The oxygen released from the sulfate anion is handed over to myoglobin in muscle cells or alpha-synuclein in neurons, and delivered to the mitochondria (safe oxygen transport).

When there isn’t enough cholesterol and sulfate to supply this process, the muscle cells become impaired in their ability to process glucose. This is the “insulin resistance” that is becoming a steadily increasing problem in modern society. Unlike the skeletal muscles, the heart muscle is protected from it, but only because the plaque is doing its job delivering a private stash of cholesterol sulfate to the heart.

The hydrogen sulfide that is produced by metabolizing glucose in the caveolae is eagerly taken up by the mitochodria of all the tissues (they prefer it over glucose as a source of energy!). The mitochondria convert hydrogen sulfide to thiosulfate, producing ATP in the process (this is well established). The thiosulfate is the source of sulfur that feeds into eNOS to produce two molecules of free sulfate from one molecule of thiosulfate (at least that’s my current model). This completes the sulfur cycle. Thus, hydrogen sulfide is oxidized to sulfate in the skin upon sun exposure (capturing the energy in sunlight), and then the sulfate is reduced back to sulfide in the caveolae of muscles (and probably also neurons), using glucose as the reducing agent.

When an individual becomes so deficient in cholesterol and sulfur and sunlight exposure that they can no longer maintain the sulfur cycle, their body converts to a nitrogen-based oxygen transport mechanism. This has the advantage that it doesn’t depend on cholesterol, but the disadvantage that nitrate does not hang out in the extracellular matrix proteins the way sulfate does. So I think it has to be continually produced and excreted through the urine. Eventually, sources of nitrogen become depleted, and the person ends up with cachexia, a muscle-wasting disease.

When you switch to nitrogen-based oxygen transport, you also have to adjust the cations to reflect the fact that nitrate is a chaotrope instead of a kosmotrope. This is why calcium entry into a cell causes eNOS to switch from producing sulfate to producing nitrate. Calcium is a kosmotrope, whereas potassium is a chaotrope. So you have the following possible pairs in the cell:


potassium-sulfate: chaotrope-kosmotrope
calcium-nitrate: kosmotrope-chaotrope


I think the system is rather elegant, because, when the cell becomes depleted in cholesterol, it starts leaking small ions through its membrane, such as potassium and sodium. It will exhaust itself, consuming all of its ATP, in trying to keep these ions on the right side of the fence. So, instead, it converts to calcium-nitrate instead of potassium-sulfate, because calcium is a much bigger ion and won’t leak. It has to switch the anions in order to balance the kosmotrope/chaotrope situation.

So, another thing that happens when you switch from sulfur-based to nitrogen-based oxygen transport is that calcium gets leached from the bones, so that it can buffer the nitrates in the blood and in the cells. Arteries become calcified (”hardened”) and heart valves become calcified, while the person simultaneously develops osteoporosis.

People’s bodies react differently to these deficiencies depending on their genotype. Many people develop a condition that reflects an attempt to raid sulfate from one or more sites in the body, in order to be able to stay with sulfur-based oxygen transport rather than switching to nitrogen-based oxygen transport. Some people develop arthritis, which raids sulfate from the ligaments surrounding joints. Other people develop digestive problems like

Crohn’s disease and colitis, which raids sulfate from the stomach lining. Other people get multiple sclerosis, raiding sulfate from the myelin sheath in axons in neurons. Other people end up with destroyed beta cells in the pancreas (type 1 diabetes) due to a depletion of heparan sulfate in the pancreas.

To summarize, I believe that cholesterol sulfate deficiency is behind many if not all of the chronic diseases facing us today. The solution to the problem is incredibly simple: eat more foods that are rich in cholesterol and sulfur, and get more sun exposure to the skin.

What do Preeclampsia, Heart Disease, and Adverse Vaccine Reactions have in Common? Cholesterol Sulfate Deficiency!

What do Preeclampsia, Heart Disease, and Adverse Vaccine Reactions have in Common? Cholesterol Sulfate Deficiency!

Those of you who have read my previous blog posts know by now that I am a big fan of cholesterol sulfate. The more I study, the more I come to realize that, more than any other factor, cholesterol sulfate deficiency is behind most of the conditions/diseases we face today. Perhaps the single largest factor contributing to cholesterol sulfate deficiency is inadequate sun exposure to the skin, combined with the interference effect of the chemicals in sunscreen.

Recently, I have been trying to learn everything I can about preeclampsia, in part because I think it is the most compelling example I have of cholesterol sulfate deficiency. Preeclampsia, also known as toxemia, is a serious condition now affecting 6-8% of pregnancies in the United States. Furthermore, a preeclampsic pregnancy is a significant risk factor (P=-0.0001) for future autism in the fetus [14]. Despite much study, the underlying cause of preeclampsia remains elusive. It begins innocently enough as elevated blood pressure and excess protein in the urine (proteinurea), but can quickly cascade into a remarkably divese set of alarming symptoms, sometimes terminating in the death of either the mother or the fetus or both.

Preeclampsia typically develops in the last trimester of pregnancy, the same period during which the placenta normally stocks up on cholesterol sulfate [11], as I have discussed previously. Is this a mere coincidence? I don’t think so! Proteinurea comes about because the glomeruli of the kidney allow large blood proteins like albumin and globulin to sneak past the sieve of their filter. An enlightening article published in the year 2000 [18] showed that such defective filtering in the kidneys is a consequence of both a decreased production of heparan sulfate and an increased breakdown of heparan sulfate by both reactive oxygen species (ROS) and active enzymes like heparanase. In my interpretation, the glomeruli are sacrificing their sulfate supply for the sake of the fetus, and this leads to a pathology in their function. In the extreme case, it can result in kidney failure, and this is one of the conditions that leads to death of the mother in severe preeclampsia.

Common Grounds in Preeclampsia and Cardiovascular Disease

There are remarkable similarities between preeclampsia and cardiovascular disease. First of all, women who develop preeclampsia are at a greater risk to cardiovascular disease later in life [20]. Secondly, the serum markers for preeclampsia and cardiovascular disease are identical – high levels of small dense LDL particles and reduced serum HDL [21], elevated blood pressure, and high serum homocysteine [13]. Finally, preeclampsia is associated with a vascular disease in the arteries of the placenta that eerily resembles the defects in the arteries supplying the heart associated with cardiovascular disease – thickening of the artery wall, smooth muscle cell proliferation, and the appearance of fatty deposits in foam cells derived from macrophages [7,10].

Since I know that the placenta needs to accumulate a huge supply of cholesterol sulfate during the third trimester, I hypothesize that the purpose of the activities in the artery wall of the diseased placenta might be to produce cholesterol sulfate. This is further supported by two of the most effective treatments for preeclampsia: heparin and magnesium sulfate injections. While it is generally believed that it’s the magnesium in magnesium sulfate that’s important, I think it could well be that the sulfate is as well. And heparin, as I’ve said before, is the most highly sulfated molecule known to biology. Interestingly, heparin is also used as a treatment for infertile women who have become pregnant through in vitro methods.

Since cardiovascular disease has been much more thoroughly studied, I turn to the cardiovascular disease literature to answer my question – I seek evidence that cholesterol sulfate is being produced in the atheroma, and, by analogy, I suggest that this is also the reason for the disturbances in the artery wall of the placenta in preeclampsia. By deduction, I propose that the need to synthesize cholesterol sulfate is the underlying cause of both conditions.

The most significant evidence comes from the known association of both conditions with elevated serum homocysteine. Homocysteine is a sulfur-containing amino acid, and, when its level is elevated in the blood, much of it gets converted to homocysteine thiolactone, which then enters the artery wall in the atheroma and attaches itself to the matrix proteins [15]. A chemical reaction requiring superoxide (ROS) as a catalyst can oxidize the sulfur atom in homocysteine to produce sulfate. This reaction is catalyzed by vitamin C, which has been shown to reduce risk to preeclampsia when used as a supplement [5] [because it would enhance the supply of sulfate and hence solve the core problem]. Reaction with ATP then produces a molecule awkwardly called 3’-phosphoadenosine 5’-phosphosulfate (PAPS) [24], which is basically an energized sulfate molecule.

Platelets, also residing in the plaque, can synthesize cholesterol sulfate from cholesterol and PAPS. Experiments conducted in vitro have shown that platelets increase their synthesis rate of cholesterol sulfate 300 fold when they are provided with PAPS [24]. Red blood cells play an important role as well, because they provide ATP to the artery wall [23]. Cells are stimulated to produce ROS when they are exposed to externally supplied ATP, and I think this is because the ATP provides the oportunity to produce PAPS, but the ROS are needed first in order to derive sulfate from homocysteine thiolactone.

Platelets are also choosey about who can deliver the cholesterol to combine with the sulfate. In fact, they will only use cholesterol provided by HDL-A1 [24]. Reduced serum HDL, as well as reduced cholesterol content in serum HDL, are strong risk factors for cardiovascular disease. I therefore think that HDL is the bottleneck in the production of cholesterol sulfate. The macrophages in the plaque perform a vital function in extracting cholesterol from damaged small dense LDL particles, buffering it internally within fatty deposits, and later exporting it into HDL-A1, whenever the opportunity presents itself [9].

Since low cholesterol in HDL is a significant risk factor for atherosclerosis, how is HDL supposed to be supplied with cholesterol normally? Fibroblasts in the skin are an important supplier, mediated by ATP-binding Cassette A1 (ABCA1), and defective ABCA1 is associated with a substantially increased risk to atherosclerosis, along with decreased efflux of cholesterol from these peripheral cells [2]. I believe that cholesterol sulfate may be an intermediary that allows cholesterol to easily migrate from the cell wall of a fibroblast to the HDL monolayer. It has been demonstrated that cholesterol sulfate moves much more freely from one lipid membrane to another than does cholesterol, largely due to its increased solubility in water (i.e., blood) [19]. Fibroblasts are among the cell types that contain eNOS, and I have argued previously that eNOS can synthesize sulfate in the presence of sunlight. So I firmly believe that sunlight exposure to the skin would help fibroblasts fill the coffers of HDL containers with cholesterol. It follows that insufficient sunlight exposure would therefore lead to depleted cholesterol supplies in HDL, and therefore increased risk to cardiovascular disease and to preeclampsia.

Nitric Oxide, Cobalamin Destruction and Pernicious Anemia

In a moment, I will show you some results I obtained by investigating adverse reaction reports from the VAERS (Vaccine Adverse Event Reporting System) database. In browsing the data, I was struck by the number of symptoms that were common in extreme vaccine reactions that are also associated with pernicious anemia. These include diarrhea, constipation, fatigue, light-headedness, appetite loss, pale skin, shortness of breath, swolen tongue, depression, loss of balance, and numbness/tingling. Pernicious anemia is due to a severe cobalamin (vitamin B12) deficiency, usually due to impaired uptake from the gut. However, cobalamin can be stored for a long time in the liver (up to a year), and so impaired uptake takes considerable time before it manifests as severe disease. In adverse vaccine reactions the symptoms come on very quickly, so it is likely to be due to a destruction of the cobalamin already present in the blood rather than to an impaired uptake.

Therefore, I sought papers that might explain how cobalamin could be destroyed. I came across several papers that discussed interactions between various oxides of nitrogen and cobalamin [8, 3, 16]. It seems that nitrous oxide (N2O), nitric oxide (NO) and peroxynitrite (ONOO−) all react with cobalamin to form various oxidized or nitrosylated derivatives. Since nitric oxide is the gas that’s produced by eNOS in the endothelium, it is the most likely candidate for our purposes, although the other two molecules will also be present as derivatives when NO is in high concentration in the blood.

Profuse nitric oxide synthesis is an expected reaction in the vasculature to exposure to endotoxins from pathogens, which are the “active ingredients” in vaccines. Furthermore, aluminum, added as an adjuvant, has also been shown to stimulate nitric oxide synthesis in the artery wall, likely due to its imitation of calcium, a well-established inducer of the reaction. A very enlightening paper [4] showed that anaphylactic shock (equivalent to an extreme adverse reaction to vaccines) can be induced in mice by exposing them to endotoxin and aluminum hydroxide. The paper elegantly demonstrated that it was eNOS (endothelial NOS, the constitutive form), not iNOS (the inducible form that macrophages produce to fight infection) which produced the profuse amounts of nitric oxide that led to anaphylactic shock. The anaphylactic shock reflects a sudden dramatic drop in blood pressure, brought on by the excess nitric oxide – a well known vasodilator. The journal editors, in an article introducing the above article [12], suggested that “agents that inhibit NOS or that scavenge NO might prove useful in treating life-threatening anaphylactic shock.” I maintain that one such agent is cobalamin!

A direct quote from a 1996 paper on nitric oxide and cobalamin says it better than I could ( [3], p. 1863): “Based on spectroscopy of urine samples, they believed that nitrosylcobalamin was formed in vivo in the mice overproducing NO as a result of endotoxin injection [34], and that the nitrosylcobalamin was being eliminated in the urine. Thus, it appears the H2O-Cbl [water-cobalamin complex] may bind NO and quench its effects both in vitro and in vivo.”

Thus cobalamin performs a useful role as a scavenger of excess nitric oxide, but then the reaction product is eliminated through the kidneys, and this will deplete the supply of cobalamin to the body. For someone who is deficient in cobalamin, this could then lead directly to a physiological state that’s indistinguishable from pernicious anemia.

Studies on the VAERS Database

I have done a number of studies of different subsets of the VAERS (Vaccine Adverse Event Recording System) database, which very nicely reveal a common thread among severe vaccine adverse reactions, autism, pernicious anemia and preeclampsia. My approach was to produce the following two datasets:

1. “Autism set:” A subset of all cases where the word “autism” or the word “autistic” show up.

2. “Anemia set:” A subset of all cases where any of the following symptoms show up: diarrhea, fatigue, light-headedness, loss of appetite, shortness of breath, swollen tongue, and numbness. These are all known symptoms of pernicious anemia.

The “autism” set consisted of 1323 events, and the “anemia” set was much larger, with over 50K events. I could then create another two sets, which I call “not-autism” and “not-anemia.” These were randomly drawn from the remainder of the (over 340,000) events, so as to maintain the same age distribution as the corresponding available sets for autism and anemia.

Now, what can be done is to count word frequencies for each of these pairs: Autism/Not-autism and Anemia/Not-anemia. Words that show up statistically significantly more frequently in the autism set or in the anemia set become words of interest, representing, collectively, other characteristics associated with the people who experienced these adverse reactions.

First of all, it’s reassuring that the word “anemia” was highly associated with the Anemia set (p=0.00074). Since we didn’t select on “anemia” itself, what this tells us is that the symptoms of anemia associate with anemia itself, as would be expected. Furthermore, the Anemia set is also an excellent predictor of autism (p=0.00066). What this tells us is either that autistic children are more likely to develop this anemia-like reaction to vaccines than other children, or that this group of symptoms is more likely to lead to autism. We can’t identify the cause-and-effect relationship, only the correlation, but it is very strong.

Another very interesting result we observed is that all of the symptoms that showed up with increased frequency in the Autism set were also highly overrepresented in the Anemia set. These include “anxiety,” “eczema,” “asthma,” “premature,” “pneumonia.” and “infection.” Thus, the Anemia set is a much larger set than the autism set which however captures the same set of conditions as the autism set, suggesting that the autism group of children are a small subset of a profile that is characterized by this anemia-like reaction to vaccines. The advantage of the Anemia set over the Autism set is that it is much larger, and therefore has a lot more statistical power in uncovering other related features.

So now, the interesting part comes when we look at additional symptoms/conditions that are over-represented in the Anemia set, beyond those present in the Autism set. I show these in Tables 1 and 2. Table 1 shows all the symptoms that are both highly overrepresented in the Anemia set and characteristic symptoms of preeclampsia. These include highly specific things like “blurry vision,” “facial swelling,” and “sensitivity to light,” as well as “pulmonary disease.” Table 2 shows additional symptoms that are over-represented in this set, which are cause for alarm, words like “seizure,” “death,” “paralysis,” and “heart failure.” These represent the final stage in a cascade reaction in the blood, when it is unable to right itself in time, following exposure to the toxins in the vaccine. They are also the extreme symptoms that show up in final stages of severe preeclampsia.

Table 1: Symptoms that occur with enhanced frequency in the anemia data set, compared with the control set, which are also known to be highly common in preeclampsia.

Reaction	Count Anemia	Count Control	P-value
Nausea	8817	3088	4.2E-14
Headache	4495	1839	9.5E-10
Abdominal Pain	945	146	8.3E-7
Anxiety	1720	728	6.7E-6
Pulmonary Disease	453	113	0.00016
Vision Blurred	420	129	0.00042
Visual Impairment	258	54	0.00069
Facial Swelling	288	162	0.015
Eye Irritation	119	50	0.022
Sensitivity to Light	70	11	0.011
Bilirubin	66	26	0.042

So all these analyses lead me to a bold generalization as follows: both preeclampsia and extreme adverse reactions to vaccines are a consequence of a profuse over-production of nitric oxide by eNOS in the artery wall. This excess nitric oxide reacts with cobalamin, which helps to neutralize its effects, but also gets taken down in the process. The blood enters a severe state of crisis following the sudden depletion of cobalamin, leading to the symptoms of pernicious anemia. eNOS is prevented from producing sulfate, and it may well be the sulfate depletion that is at least as big a problem as the overproduction of nitric oxide.

But, if you’re paying attention, you should be asking the question at this point, “How does preeclampsia end up with exuberant synthesis of nitric oxide?” I was puzzled, too, by this question, but the parallels in the symptoms make me think it must be true. I suspect it has something to do with progesterone. As you can see from the figure [25], progesterone levels shoot way up in the last trimester of pregnancy. Progesterone has a remarkable ability to prevent cells from storing cholesterol in private stores [6]. Excess progesterone in the blood would therefore cause the endothelial cells lining the artery wall to give up their cholesterol for the greater good. As we’ve seen from my previous blog post, insufficient membrane cholesterol leads to runaway leaks of small ions, and a rapid influx of calcium, which stimulates eNOS to switch from synthesizing sulfate to synthesizing nitrate. This idea has strong support from the literature [17, 22], where it has been shown that excess nitrates in the blood are associated with preeclampsia, and the amount of nitrate correlates with the severity of the disease.

Table 2: Other symptoms that were identified as highly signficantly over-represented in the anemia data set, besides those specifically associated with autism or preeclampsia.

Reaction	Count Anemia	Count Control	P-value
Sleep Disorder	534	140	0.0001
Seizure	1144	632	0.0005
Nerve Injury	69	0	0.004
Disorientation	112	32	0.01
Chest Pain	1366	278	2.0E-7
Heart Rate Irregular	963	279	1.0E-5
Heart Failure	64	8	0.01
Myalgia	981	416	0.00001
Paralysis	384	71	0.0001
Dysphagia	353	96	0.0005
Loss of Consciousness	832	447	0.001
Death	180	74	0.01

The whole point of it might simply be to spare the consumption of cholesterol and sulfur by these cells so that the fetus can have more. Such problems would only arise when there isn’t enough cholesterol sulfate to go around. Interestingly, Triton X-100, a surfactant ingredient found in the flu vaccine, has the same property as progesterone in interfering with cholesterol homeostasis in cells.

A Role for Seizures

You might imagine that preeclampsia is a precursor to eclampsia, and, if so, you would be right. You may have also noticed that “seizures” was one of the conditions that showed up with a highly significant bias (p= 0.00047) in the Anemia data set compared to the control. In rare cases, preeclampsia turns into eclampsia, a condition that is defined by the appearance of seizures. This to me is extremely intriguing, because it leads me to hypothesize that the purpose of the seizures is to generate sulfate anions. I believe this because I believe that sulfate deficiency is the root cause of preeclampsia.

How might a seizure produce a sulfate anion, and where might it come from? I think the answer is taurine! Taurine is a very unusal amino acid, the only sulfonated amino acid, and it is believed to be basically inert – an end product that happens to be stored in high concentrations throughout life in the heart, brain, and liver. These are arguably the three most important organs for survival in an emergency. I can’t imagine that these organs maintain an abundant store of a molecule that they find useless except possibly for reacting to osmosis imbalances by moving it around between cells and the blood stream. I believe instead that taurine is brought into play under conditions of extreme stress; in particular, under conditions where severe sulfate deficiency would result in a melt-down of the blood if not immediately corrected.

The sulfur in taurine is in a +5 oxidative state. It needs to be in a +6 oxidative state in order to happily live in a sulfate anion. That is, it needs to give up an electron. One thing that an electric current is very good at is pursuading molecules to give up electrons. A seizure induces an electric current! Oxygen molecules (O2) will be happy to pick up electrons given up by other molecules, thus turning into superoxide, a highly reactive molecule. I’m imagining that, in the context of an electric current, a superoxide anion steals a sulfur along with two oxygen molecules from taurine, leaving behind acetaldehyde in its wake. The sulfur atom, now at a +6 charge, is very happy to double-bond with the superoxide, magically yielding a sulfate anion! And this helps solve the brain’s crisis involving insufficient sulfate buffering. So, if this argument is right, there is a silver lining in seizures, in that they can replenish sulfate in the brain.

Summary

This blog post turned out to be a lot longer than I was expecting when I set out to write it. I’ve hit upon a number of topics, all closely intertwined in somewhat subtle ways. I started by showing the remarkable parallels between preeclampsia and cardiovascular disease, and I argued that the activities going on in cardiovascular plaque are the same as those going on in the arteries of the placenta in preeclampsia, and that both serve the purpose of producing cholesterol sulfate for their host: the heart in the one case and the fetus in the other.

My second topic was the relationship between pernicious anemia and severe adverse reactions to vaccines. Pernicious anemia is a direct result of extreme cobalamin deficiency, and in this section I showed how cobalimin would likely be destroyed if there was an overabundance of nitric oxide in the blood. This overabundance would be due to the stimulation of eNOS to produce nitric oxide in the context of both endotoxin and aluminum in the vaccine. In the case of preeclampsia, the trigger to synthesize abundant nitric oxide is brought on by a depletion of membrane cholesterol in the endothelial cells lining the artery wall. This in turn is caused by progesterone, which is well-known as an agent that leaches choesterol from cell walls, and which rises to high serum levels towards the end of pregnancy.

In the next section, I developed an argument based on studies of the VAERS database, where I showed remarkable links among autism, extreme adverse reactions to vaccines, preeclampsia, and pernicious anemia. I believe that all four of these conditions are attributable to a deficiency in cholesterol sulfate, which results in a dramatic switch from sulfate to nitrate as the anion of choice to maintain electrolyte balance in the blood. An instability brought on by the rapid depletion of cobalamin leads to the symptoms of pernicious anemia. But I think the severe depletion of sulfate in the blood may cause the disturbing symptoms that show up in extreme cases, such as paralysis, seizures, and death.

The final section addressed specifically the topic of seizures, and proposed a novel theory for a positive role seizures may play in allowing taurine to free up its sulfonate and convert it into sulfate. This is of course a critical step in recovery from the event, and so, if I’m right about this speculation, seizures likely are an important part of the solution in such situations.

References

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[2] A.D. Attie, J.P. Kastelein and M.R. Hayden, “Pivotal role of ABCA1 in reverse cholesterol transport influencing HDL levels and susceptibility to atherosclerosis,” J. Lipid Res 42:1717-1726, 2001.

[3] M Brouwer, W Chamulitrat, G Ferruzzi, DL Sauls and JB Weinberg, “Nitric oxide interactions with cobalamins: biochemical and functional consequences” Blood 88:1857-1864, 1996.

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[9] P.T. Kovanen, “Atheroma formation: defective control in the intimal round-trip of cholesterol,” Eur Heart J 11 (suppl E): 238-246, 1990.

[10] Helen Kay, MD, D. Michael Nelson, MD, Yuping Wang, MD., Ed., The Placenta: From Development to Disease, Blackwell Publishing, Ltd., 2011.

[11] B. Lin, K. Kubushiro, Y. Akiba, Y. Cui, K. Tsukazaki, S. Nozawa and M. Iwamori, “Alteration of acidic lipids in human sera during the course of pregnancy: characteristic increase in the concentration of cholesterol sulfate,” Journal of Chromatography B, 704, 99-104, 1997.

[12] C.J. Lowenstein and T. Michel, “What’s in a name? eNOS and anaphylactic shock” J Clin Invest. 116(8): 2075-2078 Aug 1, 2006.

[13] G. Makedos, A. Papanicolaou, A. Hitoglou, I. Kalogiannidis, A. Makedos, V. Vrazioti, and M. Goutzioulis, “Homocysteine, folic acid and B12 serum levels in pregnancy complicated with preeclampsia,” Arch Gynecol Obstet (2007) 275:121-124.

[14] J.R. Mann, S. McDermott, H. Bao, J. Hardin and A.Gregg, “Pre-eclampsia, birth weight, and autism spectrum disorders.” J Autism Dev Disord. 40(5):548-54, May 2010.

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