The Problematic Paradigm of LDL-C, Part 2

LDL Studies and the Association Between LDL-C and Heart Disease, pt. 1

Previous - Part 1 - The Development of the Lipid-Heart and Diet-Heart Hypotheses

With a background understanding of how and why the lipid-heart and diet-heart hypotheses began to develop, we’ll now look at the research of the time, followed by more recent examples, that both do and do not support the general thesis of the LDL-disease paradigm. As mentioned in the previous installment, one significant study to be published during the rise of Keys, the AHA, and the general cholesterol paradigm was the Framingham study. An ongoing effort that persists to this day, the initial results were reported in 1957 and detailed a general relationship between cholesterol levels and future cardiac events. We’ll start with Framingham before examining several other lines of research concerned with the relationships between saturated fat, cholesterol levels, and heart disease.

Framingham

The Framingham Heart Study is an ongoing cardiovascular disease project that has been tracking, and continues to track, heart disease for the last several decades. The first published results, a 4-year follow up of middle-age Americans, were made available in 1957. Among the published results was a comparison of total cholesterol levels and atherosclerotic heart disease in men over the age of 45. A couple relevant notes – Frist, science in the 1950s tended to use “people” as a synonym for “middle-age white men who smoked a lot.” That’s not meant to discredit the results, just a note of interest. Second, this study predated the technique and practice to specifically measure LDL cholesterol, and instead used the slightly less meaningful total cholesterol. We’ll define and describe all the relevant terms in a coming section, but for now total cholesterol can be thought of as LDL-C plus HDL-C plus a small contribution from triglycerides.

What these results showed was simply that the men with total cholesterol over 260 mg/dl suffered more frequent heart disease during the 4-year follow up than those with lower cholesterol (for reference, standard guidelines today typically recommend a total cholesterol below 200mg/dl). Similar patterns were noted for elevated blood pressure and obesity. While not a specific measure of LDL cholesterol and not as “scientific” as modern research (this was simply a measuring and counting exercise), the pattern was nonetheless unmistakable – those men with elevated total cholesterol were more likely to suffer future heart disease. At a time when the lipid-heart hypothesis was still gaining credence, these results were instrumental in cementing its place in medical and public consciousness.^1,2

Minnesota Coronary Experiment

While the Framingham study was only observational, the Minnesota Coronary Experiment was a well-designed randomized controlled trial, or RCT. This means that subjects were “controlled” for a long period of time in their dietary habits, with results being tracked over time. In this case, the study was conducted on some 10,000 Minnesota mental health patients, whose diet and life were easily controlled, measured, and tracked. Half of the subjects ate food cooked and served with highly saturated fats like butter, while the other half consumed the same food cooked and served with generally unsaturated fats like corn oil and margarine.

What also made the MCE experiment notable was that it the brainchild of Ancel Keys, who designed the study in an effort to validate his beliefs that saturated fat consumption drove cholesterol levels and heart disease. In 1973, after five years of intervention and tracking, data was published demonstrating that the intervention (unsaturated fat) group did indeed have lower LDL-cholesterol levels (LDL-C measures were now common, unlike during the initial Framingham results). While LDL-C levels had fallen only 4 mg/dl in the saturated fat group, they had fallen 32 mg/dl on average in the intervention group. Perhaps Keys was right! This did in fact seem to validate, to at least some degree, the notion that saturated fat consumption influenced cholesterol levels.

You may be already asking the next relevant question – what about disease and death? After all, lower cholesterol is supposed to portend protection from heart disease. Well, that data was simply not published at the time. In fact, it remained unpublished for decades. Only in the last decade, with the death of Keys and his primary co-researcher, were these results made public by his collaborator’s son, who “rescued” the raw data from his father’s personal computer.

The findings may explain why data on death and disease was never published by Keys. That extra 30 mg/dl drop in LDL-C had not in fact saved lives, but was actually associated with a 22% increase in all-cause mortality. Had these results seen the light of day in the early 70s, they may have helped influence a different nutritional landscape in the years that followed. Instead, the data only on LDL lowering, on top of the Framingham results and multifaced efforts to demonize saturated fat, helped end any and all reasonable debate on the nature of heart disease. The fraudulent efforts of Keys, beginning years earlier with a fabricated relationship between fat consumption and disease, continued, as did the now-entrenched notion that saturated fat must be avoided to prevent heart disease.^3,4

Other Early Studies

The MCE was not the only large trial of the time designed to prove the diet-heart and lipid-heart hypotheses and, believe it or not, was not the only one to hide its undesirable results.

The Sydney Diet-Heart Study was another large RCT designed to explore the effects of replacing saturated fats with unsaturated vegetable oils. The results of the SDHS were also slated to be published in 1973. Instead, all that was published was the following:

“It is concluded that because of multiple changes in lifestyle men who have had myocardial infarction are not a good choice for testing the lipid hypothesis” ⁵

After seven years (and who knows how much effort and money) of designing and tracking dietary intervention in a population chosen by the researches, all they decided to publish was an excuse that their chosen population was inappropriate for studying the topic at hand.

Again, the full results eventually became public and, again, they likely betray the reason the researchers chose to hide them in the first place. The SDHS, like the MCE, was not designed to seek objective truth, but to validate a subjective truth that had already been pre-ordained. So when the data showed that the interventional vegetable oil group was 70% more likely to suffer cardiovascular disease and 62% more likely to die, the researches chose to blame their methodology instead.⁶

This is not to say that every study found an increased rate of death and disease in subjects replacing saturated fat. The Oslo Diet Heart Study was perhaps the most prominent study that did not confirm the (hidden) results of the MCE and the SDHS. Instead, 206 heart attack patients consuming a self-selected diet were compared to 206 similar patients consuming a controlled diet rich in unsaturated vegetable oil. The results? In 11 years, the self-selected diet group saw 102 cardiovascular disease deaths and 5 from other disease, while the vegetable oil group saw 88 cardiovascular disease deaths and 12 from other disease, for an approximately 14 percent decrease in cardiovascular mortality and a 7 percent decrease in all disease-related mortality.⁷

With Framingham and Oslo published and promoted and the MCE and SDHS covered up, the inescapable scientific conclusion of the time confirmed what Keys, the AHA, the government, and many doctors of the time already believed – saturated fat must be minimized in order to lower cholesterol levels and prevent death and disease.

** This part is purely my opinion: The Oslo study is absolutely horrible. Why? Because there is no real control group. The MCE and SDHS, for example, controlled the diet of both groups. This means that total calorie consumption, total sugar and carbohydrate consumption, nutrient density, etc. were all roughly equal between the two groups, and the difference in fat could be better assessed as the reason for any differences. Oslo didn’t do that. They simply let the control group eat whatever they wanted and made no effort to track it, while tracking every aspect of the intervention diet. So while the interventional high-vegetable oil group suffered slightly less disease, there isn’t really anything relevant to compare it to. This is a common problem even in modern science, where a population will go from a self-selected diet to one that’s fully controlled. Low-fat, low-carb, vegan, keto, whatever…but the researchers don’t control for calories. So any difference they find after the intervention could, in theory, be attributable to a decrease in calories rather than the dietary pattern the researchers are trying to assess. Because those in the Oslo study went from a self-selected “heart attack diet” to one entirely controlled by the researchers, it is entirely possible that the reduction in disease mortality was due to the intended intervention itself, but… it could also be due a reduction in calories or sugar or something else, and we have no possible way to know that. The increased mortality of the vegetable oil groups in the better-designed MCE and SDHS lend credence to the theory that vegetable oil is not the reason for the decreased mortality in the Oslo study. In fact, it may be the case that the vegetable oil is still causing excess disease, but that this effect is more than counterbalanced by the reduction in disease caused by a decrease in calories, sugar, or any change the researchers aren’t measuring or reporting.

Part 3 - LDL Studies and the Association Between LDL-C and Heart Disease, pt.2

 

 

 

1.           Framingham Heart Study. In: Wikipedia. ; 2022. Accessed December 14, 2022. https://en.wikipedia.org/w/index.php?title=Framingham_Heart_Study&oldid=1126493920
2.           Dawber TR, Moore FE, Mann GV. II. Coronary Heart Disease in the Framingham Study. Am J Public Health Nations Health. 1957;47(4 Pt 2):4-24.
3.           Frantz ID, Dawson EA, Ashman PL, et al. Test of effect of lipid lowering by diet on cardiovascular risk. The Minnesota Coronary Survey. Arteriosclerosis. 1989;9(1):129-135. doi:10.1161/01.atv.9.1.129
4.           Ramsden CE, Zamora D, Majchrzak-Hong S, et al. Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73). BMJ. 2016;353:i1246. doi:10.1136/bmj.i1246
5.           Woodhill JM, Palmer AJ, Leelarthaepin B, McGilchrist C, Blacket RB. Low Fat, Low Cholesterol Diet in Secondary Prevention of Coronary Heart Disease. In: Kritchevsky D, Paoletti R, Holmes WL, eds. Drugs, Lipid Metabolism, and Atherosclerosis. Advances in Experimental Medicine and Biology. Springer US; 1978:317-330. doi:10.1007/978-1-4684-0967-3_18
6.           Ramsden CE, Zamora D, Leelarthaepin B, et al. Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis. BMJ. 2013;346:e8707. doi:10.1136/bmj.e8707
7.           Leren P. The Oslo Diet-Heart Study. Circulation. 1970;42(5):935-942. doi:10.1161/01.CIR.42.5.935

The Problematic Paradigm of LDL-C, Part 1

The Development of the Lipid-Heart and Diet-Heart Hypotheses

The lipid-heart and diet-heart hypotheses. The average person may not know them by their name, but certainly everybody knows them in some capacity or another. Quite simply, their combined assertion is this: consuming dietary fat and cholesterol causes cholesterol levels in the blood to rise, and these rising levels of cholesterol are the primary factor in the development of heart disease. Put even more simply – eat too much fat, risk a heart attack.

This singular basic message has formed the backbone of nutrition and dietary advice for decades, for as long as most who will read this have been alive. One would be forgiven if, somewhere along a road lined with high-school health classes, heart-healthy checkmarks, and ubiquitous advertisements for low-fat yogurt and statins, that these ideas were settled science existing in a space far beyond any credible doubt. But what makes the longevity of these twin concepts so notable is both the absence of strong evidence to support the assertions, and the incredible simplicity of the model that allows them to persist unabated nonetheless.

The simplicity is apparent and approachable – eating fat and cholesterol causes cholesterol to accumulate in the bloodstream, where it…. gets stuck, basically. The mechanics of WHY cholesterol behaves this way are less apparent and rarely explained, but it seems the basic idea presented to the public is simply that cholesterol is a sticky substance that, in large amounts, inevitably attaches itself to the walls of the arteries and blocks the normal flow of blood. Obviously, things are not this simple. Likely surprising to many, cholesterol does not exist “in” the bloodstream at all, but in carrier “boats” called lipoproteins, and so the basic construct by which it sticks to the blood vessels needs at least some greater level of detail. In fact, it requires a much greater level of detail, which will be explored over the course of this series of posts.

But before exploring the realities of cholesterol and the failures of the lipid-heart and diet-heart hypotheses, one needs to understand where these parallel concepts came from and the factors that allowed them to thrive.

Some 70 years ago, as it is today, heart disease was a common killer in western society. Autopsies of young soldiers killed in action found significant atherosclerosis, artery-clogging deposits that contained, among other things, a waxy substance known as cholesterol. In an era that still saw doctors recommending their preferred brand of cigarette, the heavy rates of smoking among these young soldiers and the population at large didn’t jump off the page as an obvious candidate in the search for the heart-stopping culprit.

Around the same time, a University of Minnesota physiologist named Ancel Keys presented to the World Health Organization his theory that the consumption of fat (saturated fat from animal products in particular) was the primary factor in the development of cardiovascular disease. To support this claim, Keys hand-selected six countries, from a complete dataset of about two dozen, that allowed him to draw the most pronounced connection between increasing fat consumption and increasing heart disease. This extremely biased methodological error, in which Keys dismissed all available data contradicting his beliefs, led him to be publicly refuted in his original attempt at promoting his idea.¹

2

However, other factors were also developing that would eventually assist Keys in his effort to demonize the consumption of saturated fat. In 1911, while attempting to use vegetable oil as a base for soapmaking, the company Proctor and Gamble inadvertently discovered that they could create a partially solid product that reasonably resembled butter at room temperature. Vegetable oils, previously used primarily as industrial lubricants, were suddenly an appealing option for the creation of a cheap, shelf-stable, butter-like compound that could be marketed as a cooking product. Thus was born Crisco, an industrially-produced product with little saturated fat.³

For the next couple of decades, sales grew steadily as P&G marketed their butter-replacement product as a cheaper, easier cooking alternative. However, their big moment came in 1948 with their large donation to a fledgling non-profit known as the American Heart Association. On the back of this cash influx, the AHA, presided over at this time by Dr. Paul Dudley White, would go from an organization with little influence or notoriety to the largest non-profit in the nation in just more than a decade.^4,5

In 1955, during the AHA’s rise to prominence, President Dwight D. Eisenhower, himself a heavy smoker, suffered a heart attack that would be instrumental in shaping the American dietary paradigm. His personal doctor, the same Dr. White who presided over the AHA during the Crisco partnership and who was himself unsurprisingly opposed to saturated fat consumption, entrusted the role of the President’s personal nutrition advisor to the like-minded Ancel Keys. Eisenhower bought in to the “prudent diet” approach being offered by Keys, whose relationship with the popular president helped push him and his ideas forward in the American consciousness.^6,7

Now in lockstep with the President, Keys and the ever-growing AHA led a national charge to erase the menace of heart disease from American society. Within years of President Eisenhower’s heart attack, Keys was featured on the cover of TIME magazine as an expert on diet and heart health, while the AHA formalized guidance that saturated fat consumption should be strictly limited for the prevention of heart disease. These guidelines, based on effectively no clinical evidence, did not yet push for the elimination of all fat from the diet, arguing that the replacement of saturated fat with polyunsaturated fats such as Crisco would do the trick. As we will see in the next section, clinical trials launched after the fact were meant to validate the guidelines already put in place, but failed notably in this endeavor.

Unfortunately for President Eisenhower, the prudent diet approach assigned by Keys was ineffective, as he would go on to suffer multiple additional heart attacks, a stroke, and develop diabetes before his death from obstructive coronary disease. Now, much of this declining health is again likely attributable to smoking, but it is without question that the public face of America’s new low-fat diet experiment fell well short of resounding success.

Meanwhile, scientists such as John Yudkin advocated not for a low-fat, but instead a low-sugar approach to dietary intervention. In the mid-1960s, a series of studies pointing towards sugar as the primary driver of cardiovascular disease helped, briefly at least, keep alive the fat vs sugar debate. In an effort to combat the impact of these studies the research director of the Sugar Research Foundation, John Hickson, paid two Harvard scientists to author editorials in the New England Journal of Medicine that would discredit the research and exonerate sugar as a disease-causing agent. One of these scientists would become an administrator for the USDA, while the other would lead the Kellogg’s-funded nutrition foundation at Harvard.^8,9

Efforts such as these, combined with the growing prominence of Keys and his like-minded followers, the influence of the AHA, and the full resolve of the US government, helped cement the lipid-heart and diet-heart hypotheses as the standard dietary paradigm. While evidence was still extremely limited, one major observational study had now confirmed a general association between cholesterol and heart disease (the Framingham study, which we’ll examine in detail in the next section), with the promise of more and better research to come being promoted by Keys and others. While some of these research efforts would ultimately do more to discredit than to confirm the attack on saturated fat and LDL cholesterol levels, they would not do so until such notions were firmly entrenched in the minds of scientists, health care professionals, and the general public.

The lipid-heart and diet-heart hypotheses, weak and unsupported as they may be, were here to stay.

Part 2 – LDL Studies and the Association Between LDL-C and Heart Disease, pt.1

 

1.               1957_Yerushalmy_Hilleboe_Fat_Diet_Mortality_Heart_Disease.pdf. Accessed December 12, 2022. http://library.crossfit.com/free/pdf/1957_Yerushalmy_Hilleboe_Fat_Diet_Mortality_Heart_Disease.pdf
2.               Deep Nutrition: Why Your Genes Need Traditional Food - Catherine Shanahan, M.D. - Google Books. Accessed December 12, 2022. https://books.google.com/books?hl=en&lr=&id=1fs3DAAAQBAJ&oi=fnd&pg=PP1&dq=deep+nutrition+cate+shanahan&ots=YNQWfUTs9a&sig=tVMLoLV8CQ34Lhsq4Rduo__tQdg#v=onepage&q=deep%20nutrition%20cate%20shanahan&f=false
3.               MSEd LWB. This Is How Crisco Is Really Made. Mashed. Published July 9, 2020. Accessed December 12, 2022. https://www.mashed.com/224919/this-is-how-crisco-is-really-made/
4.               History-of-the-American-Heart-Association.pdf. Accessed December 12, 2022. https://www.heart.org/-/media/Files/About-Us/History/History-of-the-American-Heart-Association.pdf
5.               Teicholz N. The Big Fat Surprise: Why Butter, Meat and Cheese Belong in a Healthy Diet. Simon and Schuster; 2014.
6.               Dwight Eisenhower: Treating his Heart Attack. Accessed December 12, 2022. https://doctorzebra.com/prez/z_x34mirx_g.htm
7.               Paul Dudley White. In: Wikipedia. ; 2022. Accessed December 12, 2022. https://en.wikipedia.org/w/index.php?title=Paul_Dudley_White&oldid=1125479668
8.               Taubes G. The Case against Sugar. First edition. Alfred A. Knopf; 2016.
9.               Fredrick J. Stare. In: Wikipedia. ; 2022. Accessed December 12, 2022. https://en.wikipedia.org/w/index.php?title=Fredrick_J._Stare&oldid=1079782061

The Problematic Paradigm of LDL-C, Introduction

 

As was mentioned in this blog’s introductory post, much of what will be written on here will be expansive pieces on health and nutrition, designed to be both in-depth but also accessible to somebody with no background in topics related to health, physiology, or nutrition. Future topics will likely include, among others – why epidemiology (ie. observational study) is mostly junk science, why meat is certainly not causing cancer, why animals are not driving climate change, various aspects of chronic disease, the relationships between extreme exercise and health, why vegetables oils will lower your cholesterol but probably also contribute to killing you, why vegetables aren’t all they’re cracked up to be, and why your health will likely improve if you eat a bunch of them anyway.

However, the first topic that will be explored, likely over the course of the next 2-3 months, is cholesterol and cardiovascular disease. Cardiovascular disease is probably the most prominent chronic disease in the modern consciousness and the disease at which most dietary and nutrition advice has been aimed over the last several decades. Simply put, I believe the bulk of that advice has been and remains erroneous and actively harmful to those subscribing to its tenants, and has been far more effective at promoting massive commercial and pharmaceutical interests than it has at improving health or preventing disease.

I have already written a lengthy paper on the subject of lipid metabolism, cholesterol, and cardiovascular disease, which can be found here. However, this paper almost certainly suffers from the aforementioned problem of inaccessibility. My hope here, over the next several weeks, is to explain in lay terms the paper’s thesis and its implications for cardiovascular disease and human nutrition. I intend for this to be a roughly ten-part series on all things cholesterol, beginning with the necessary background information before walking through the behavior and mechanics of lipids and the dietary choices that drive these observations. This introductory post will serve as a table of contents of sorts, with part 1 coming shortly.

Part 1 - The Development of the Lipid-Heart and Diet-Heart Hypotheses 

Part 2 - LDL Studies and the Association Between LDL-C and Heart Disease, Pt. 1

Part 3 - LDL Studies and the Association between LDL-C and Heart Disease, Pt. 2

Part 4 - Lipids and Cholesterol: Who Are the Players and What Are We Really Measuring?

Part 5 - An Energy Delivery Model: Triglyceride Production and Utilization

Part 6 - An Energy Delivery Model: The Consequences of Poor Triglycerides Utilization

Part 7 - An Energy Delivery Model: Efficient Triglyceride Uptake and an Increased Energy Demand

Part 8 - An Energy Delivery Model: The Contrasting Presentations of Elevated LDL-C

Part 9 - An Energy Delivery Model: The Downstream Consequences of an Impaired Energy Delivery System

Part 10 - Other Factors in the Development of Atherosclerosis

Part 11 - The Effects of Diet on Markers of Cardiovascular and Metabolic Health

Part 12 - The Effects of Diet on LDL-C, As Told By Energy Delivery

Is It Neuropsychiatric Systemic Lupus Erythematosus (NPSLE)?

I don’t know. Maybe?

I have no idea what’s actually wrong with me (I can’t write that in the past tense yet, unfortunately).

This post is meant to explore my opinions on what I’ve potentially been dealing with since becoming extremely sick following vaccination with the Pfizer covid vaccine. It’s kind of a weird spot presenting this to people, where if you’re a layperson I’ll probably be touching on concepts of health and medicine with which you aren’t familiar. And if you’re a medical professional, well….I at least hope you read this with an open mind. I very much welcome your input or ideas. 

Anyway… I didn’t title this post the way I did because I absolutely believe I have (or have had) neuro-lupus, but because I certainly believe it’s a possibility and have had it at least suggested by a rheumatologist. I do very strongly believe I have an autoimmune condition. NPSLE is one possibility.

Neuropsychiatric lupus is a particular manifestation of systemic lupus erythematosus (SLE), characterized by nervous system disorders. You can read about the symptoms here if you want – they include headache, aseptic meningitis, cognitive dysfunction, delirium, autonomic dysfunction, and peripheral nerve issues.¹

The Evidence for NPSLE

Anti-Sm and ANA

The argument that I have NPSLE specifically boils down to a couple key points. One is my symptom presentation, which, particularly before significant dietary intervention, matched many of the symptoms characteristic of NPSLE. I’ll outline them all at the bottom, but if you’ve already read the main introductory post I made you’re largely familiar with many of them.

The second key point is the (inconstant, to be clear!) abnormal autoimmune results potentially suggestive of lupus or an associated condition. Arguably the most important of these are the Anti-Sm antibodies, as they are most specific to lupus. In fact, studies demonstrate that a finding of positive Anti-Sm is 98-99% specific for lupus.^2,3 Anti-Sm isn’t always positive in lupus patients, but it is only rarely positive for any other reason.^2–4 Once that marker is positive, I don’t really believe “not Lupus” can remain such a strong default assumption. At the very least a very valid reason for why it is not Lupus should be proposed, which is something I don’t feel like I’ve received. At the same time, I was also positive for two other markers commonly associated with lupus and other similar conditions, like mixed connective tissue disease.

The rheumatologist who ordered those labs was hesitant to make any diagnosis because at the time of the positive anti-Sm result, I paradoxically did not have a positive ANA result (any longer. It had been positive on a previous occasion). ANA – anti-nuclear antibodies – is the most “general” autoimmune marker, so to speak, and is often used as an initial screening tool to check for possible autoimmune disease. More often than not, ANA will be positive in a patient with an autoimmune condition.

Here's where we get to a bit of opinion and speculation – “more often than not” is, to me, the important part of that last sentence. In my experience, both speaking to doctors and reading public info such as the lupus foundation website, its widely believed that ANA must virtually always be positive if a patient is to have an autoimmune condition.⁵ But…This position really isn’t supported by the literature.

I suspect this misconception results from a population-wide conflation of “ANA is a general autoimmune screening tool” with “It can’t be an autoimmune disease if the patient doesn’t have positive ANA.” It feels like doctors get in the habit of always checking ANA first and either forget or have no idea that ANA is far from definitive. I also suspect this is a one of the reasons that it takes an average of SIX YEARS from first symptom for a patient to be accurately diagnosed with lupus.⁶ I have serious doubts that a lot of physicians are well-read on the literature, including…

A study that finds “ANA-negative SLE is more common than generally realized” ⁷

A study that finds “a considerable portion of Swedish patients with SLE lose ANA-positivity over time” ⁸

A lengthy follow-up study found that that only 17 percent (!!!!) of patients previously diagnosed with NPSLE continued to return a positive ANA test.⁹

There’s actually quite a bit of literature detailing the inconsistent, fluctuating, unreliable nature of ANA as a marker of lupus and similar conditions.^10–15

What does that mean for me? I don’t know! I think it means I may very well have been diagnosed with NPSLE had only my positive ANA occurred in concert with my other positive autoimmune results. I think it means I may very well have been diagnosed with NPSLE if my rheumatologist was aware that positive ANA frequently fluctuates and fades. I think it means that SOMEBODY should at least try to answer my questions about this research rather than shut them down.  

 

Diet and Autoimmunity

My health began changing for the better with strict carbohydrate (ie. plant) restriction, with many or most seemingly benign plants apparently capable of triggering symptom flares and relapses.

Here’s the part that most people and medical professionals are apt to consider controversial – eating plants is horrible for autoimmune disease, and frankly I think most plants are an overall negative influence on health in general. Mainstream advice is obviously not going to agree with this statement, but I don’t consider that advice to be particularly evidence-based.^16,17 The primary reason plant consumption is detrimental in the instance of autoimmune disease is the presence of immune-triggering defense chemicals such as lectins.

Quick non-scientific overview of plant defense chemicals – Every organism on earth evolved to still be alive and keep reproducing and every organism has strategies and adaptations to help with the “staying alive” part. Animals have active defense mechanisms – horns, wings, speed, camouflage, etc. Plants can’t really move or fight back, so their defense mechanisms are largely passive. These are the chemical compounds – lectins, gluten, oxalates, etc. - designed to make themselves more difficult to digest and make you sick if you eat them. If you walk out into a field and try to eat a stalk of wheat, you will feel sick. You will be disinclined to eat it a second time, and the rest of the wheat will keep living. That’s how the process is supposed to work. Modern humans have obviously messed with the process pretty significantly, but a machine pre-digesting some of the wheat for you doesn’t make it healthy.

The major general exception to this paradigm is fruit. Do you know why fruit is bright and colorful and sweet? That’s because it “wants” you to eat it, so you can poop out the seeds (pre-fertilized!) somewhere new. That’s also why unripe fruit is green and bitter and more difficult to eat – it doesn’t want to be eaten yet! The ripening process includes a breakdown of the defense chemicals that might otherwise harm you if you eat the fruit too early. Green things do not want to be eaten!! That’s literally the reason green and brown things are green and brown – blending in is a survival mechanism. Turning blue or red is a survival mechanism too, one that makes fruit significantly less harmful than other plants for people with or without autoimmune disease.

Part of the argument for the health benefits of vegetables is actually that these compounds make you “stronger” by stimulating that immune response. Kinda like exercise might. That’s all a discussion for another time, but for now I’m going to link to a couple dozen papers below for anybody that wants to read about how these plant compounds adversely affect the immune system and how those with autoimmune disease frequently improve with the removal of various plants from their diet, or by fasting.^18–49

I’ll highlight one study in particular – to my knowledge the only study that placed participants on a strict lectin elimination diet and tracked markers of autoimmune disease.⁵⁰ 102 participants with various serologically confirmed autoimmune disease (lupus and others) were followed for nine months, at the end of which more than ninety percent of subjects were negative for all autoimmune markers. Eighty percent of patients had improved enough to cease all medication.

The reason I highlight that finding is because not only does it reflect how I’ve been eating, but very crucially it reflects how I was already eating for months before I was tested for any autoimmune markers. For the first several months of this ordeal, I was down a neurology rabbit hole or sorts, and so I have no autoimmune testing from anything really even resembling the worst of it. In fact Anti-sm, that lupus-specific marker, is known to correlate with flares and disease severity, and became negative as I felt amazing at the end of a week of continuous fasting.^51–53

At this point it should be clear that I’m of the opinion that the “insufficiency” of my autoimmune markers very plausibly reflects both an improvement in health and a decrease in markers that should absolutely be expected in a person consuming a diet of primarily meat and no grains, vegetables, etc. I’m also of the opinion that the massive moderating effect of diet on my symptoms is strong evidence that my issues are likely autoimmune in nature. With all that in mind – the stark effect of diet on my symptom presentation, the various adverse autoimmune markers, the dramatic neurological nature of my condition, and other factors we haven’t touched on here – I have a hard time believing my (primary) condition can be anything other than neuro-autoimmune in nature.

This post is focused on NPSLE specifically not because I’m literally making the argument that it has to be neruo-lupus or even that its highly probable I have neruo-lupus. It is because my symptoms, bloodwork, and rheumatologist’s comments all suggest the possibility, and because I think that possibility far better reflects the severity of the situation than does the common physician desire to pretend I’m just tired and dismiss everything as “long covid.” 

 

Other Possibilities

A quick overview of some other explanations I find varying degrees of plausible. Note that these aren’t mutually exclusive – an autoimmune condition doesn’t necessarily preclude some kind of nerve damage, for example.

·       Other autoimmune problems - Anti-ACE2 or similar: ACE2 is an enzyme primarily located in the blood vessels that happens to be the main method by which covid-19 binds and enters your body. There’s some research showing that long covid patients with neurological complications have near universally present anti-ACE2 antibodies. Problem is there are no labs in the US that test for these antibodies, so I have no idea if I have or had them myself. Many other long covid and post-vaccine injury patients have reported antibodies to ACE2 and other related proteins, though, so there exists the possibility that this is actually the root problem. I don’t exactly know how to connect this possibility to the neurological presentation, but there is some ACE2 expression in the nervous system so it seems plausible. In this case it would be presumed that the other abnormal autoimmune results I’ve returned are largely cross-reactive/incidental rather than a primary issue.^54–64

·       Craniocervical Instability (CCI): This would be some kind of nerve damage/compression/irritation/etc. that results from connective tissue damage to the neck. Essentially connective tissue damage leads to a weak/unstable neck, in turn leading to compression or irritation of the spinal cord and cranial nerves, in turn leading to all the neurological symptoms. The biggest reasons to consider this possibility are: 1) The autoimmune markers are suggestive of potential connective tissue problems, 2) Neck pain is my most persistent symptom, 3) Neck pain/weakness/instability is one of the most frequently reported symptoms in those with vaccine injuries, 4) Posture and position has a noticeable effect on symptom presentation, 5) CCI is increasingly thought to be common in chronic fatigue syndrome. Which is obviously different than what I’m dealing with but certainly can be thought of as similar – a lot of people think “long covid” is really just CFS, for whatever that’s worth. I again don’t believe this can make sense as the sole explanation for my condition but I think it (or something similar) is a reasonably likely secondary issue.

·       Lasting neurological damage: I don’t actually know what this would look like, but I think it must be considered a distinct possibility that I could have some yet undetected nervous system damage. The fact that my symptoms have been so highly amendable to diet and lifestyle intervention leads me to want to disregard this as a primary issue, but as higher levels of cognition become the most persistent impediment to normalcy it certainly has to be considered a distinct possibility. 

·       Depression: I’m kidding. It’s not fucking depression. But four different medical professionals have floated the idea so here we are.

Symptoms

 

Below is a fairly complete list of symptoms I’ve experienced. At this point really only the neck pain persists on a day-to-day basis, with some headache/nausea if it’s bad enough. The vast majority of these symptoms are in the past though, or only subject to significant cognitive strain. 

It all seems kind of benign when I write it out like this, as if words like “headache” and “dizziness” and “nausea” could ever capture the sensation of a brain being ripped apart from within. When it takes an hour to get from the couch to the bed, as it sometimes did, there’s really nothing that can convey how miserable that hour really is – how electric and painful it is, how completely detached from reality it feels, how absolutely heavy everything feels when you try to move, how badly it makes you wish for death. And then, ironically, when I’ve finally dragged my body to bed, how fucking certain I am that death is what awaits me as I drift to sleep.

If you’re a medical professional reading this (even a year or two after it was posted), I really do welcome your opinion. If you’ve made it all the way through both this and the first intro post you have now given this more thought, and have a more complete picture, than most of the ~15 doctors I’ve seen in the last year and a half. Main clinical abnormalities – intermittently positive ANA, Anti-Sm, Anti-Ro, Anti-U1 RNP, PR3, elevated IL6. Also found a compound heterozygous MTHFR gene mutation that may or may not have any bearing on my health at all, and have been assessed to have some kind of potential/probable/mild generalized hypermobility or hEDS. Fire away with thoughts or questions.

 

·       Headache/migraine – This is the easiest place to start. Occipital pain has been consistent throughout, with more “standard” temporal headaches occurring frequently. I use the word “migraine” here to refer to severe headache accompanied by nausea. Frequently, especially when symptoms have been generally worse, the pain has been far more electric and diffuse in nature. Powerful shooting pain that would quickly dart around was not uncommon.

·       Brain tremors? – Not technically but I don’t know what else to call it. Have you ever been stressed or didn’t sleep well and ended up with an eyelid that wouldn’t stop twitching? Imagine that feeling, but deep in the center of your brain. It’s like an electrical flickering, but instead of just feeling twitchy it also hurts and seems to short-circuit thoughts and emotions every couple of seconds. This tended to present only during the worst stretches.

·       Persistent cervical spine pain – My neck has hurt pretty much 24/7 for the last year and a half. Its far from my worst symptom, but definitely one of the most consistent. The pain is highly localized to the central spinal column and is made moderately/progressively worse by unfavorable posture but significantly worse by acute mental strain. The other component is how susceptible my neck is to “falling asleep” with any significant deviation from neutral, like your arm would if you slept on it wrong. And that’s basically what it feels like in my neck and head. Sitting much is the most problematic trigger.

·       Nausea – seemingly secondary to the headaches

·       Dizziness

·       Shakiness/tremors in the extremities

·       Numbness and tingling in the extremities

·       Weakness/neuromuscular failure

·       Constant sympathetic activation – This is the “fight of flight” response, the stimulating half of your autonomic nervous system. Physical manifestations have included persistently elevated body temperature, blood pressure, racing heart rate, etc.

·       Trigeminal neuralgia – acute bouts of sharp, stabbing facial pain presumably related to damage or dysfunction of the nerve innervating that area

·       Chest pain and palpitations – This might be the closest thing to a non-neurological symptom. But given the persistent presentation of the previous pair of symptoms, I think these are probably are just resultant from vagus never irritation/dysfunction

·       Deficits of balance and coordination – When overall presentation was worse, I would struggle consistently with balance and coordination. However, this effect was only ever extreme upon waking. Particularly before dietary intervention, I would struggle mightily with standing and walking in the minutes after waking. This would leave me frequently collapsing while attempting to get out of bed, and navigating stairs either down on my butt or up on all fours to avoid tumbling down.

·       Deficits of cognition – Independent of the brain twitching. There’s probably a better way to label that, because its certainly more severe than the “brain fog” I suffered immediately after the acute covid infection. It’s more of a complete failure of executive function. This would occur acutely and regularly when overall presentation was bad, and leave me generally incapacitated for a bout of time. I don’t know how to explain what it feels like to not be able to put together complete thoughts or sentences, but that’s basically what was happening. This was usually or always accompanied by extreme cervical warmth.

·       Acutely sharp cerebral pain – This would usually occur while walking or moving around, and was characterized by extreme, localized pain somewhere in my head. It tended to only last for a handful of moments, was always accompanied by pronounced lightheadedness, and would routinely bring me to my knees.

·       Intrusive thoughts – I don’t know what to call them. This was probably my least favorite symptom, that I’ve thankfully been more or less free from in the last 6-8 months. I would routinely experience vivid, unwanted…visions? Thoughts? Of events that usually involved my death or the death of somebody close to me. The worst episodes were the ones in which I was somehow responsible for harm to my wife or parents. The sight of almost anything that could be dangerous or used as a weapon would trigger these thoughts. I struggled in the kitchen, because I couldn’t see the sink without also seeing my hand ripped off by the garbage disposal. I couldn’t see the knife block without seeing myself stabbing somebody. I could be driving down the road thinking about something else entirely when any random car passing would trigger the vision of that car running over my dad on his bike. I really don’t know how to describe these events other than to say that they seemed so distinctly different than normal “imagination.” They seemed much more viscerally real, and something I had simply no control over.

·       Psychosis? – Again, I don’t know what to actually call it. The main presentation here was a complete inability to separate sleep from death. For months I literally lost the capacity to understand on a cognitive or emotional level what was happening when I went to sleep. Which I’m sure sounds very weird, and I’m sure I’m not going to be able to describe it well. When I would get closer to falling asleep, it seemed my connection to reality would fade away. Every single night, and every single nap, I simply KNEW that I was dying. I always felt a weird mix of panic and desperate desire to come to terms with what was happening before I slipped away. This would also happen regularly upon waking, wherein I would also be sure I was about to die as I woke up. I would often find myself looking around for who or what was going to kill me, or I would be plagued by a sensation that I would drop dead as soon I tried to stand up. This obviously made sleep more difficult that it needed to be, and I still can’t really go to sleep without listening to a podcast so as to avoid the uncomfortable sensation of being “alone” in the situation I largely came to associate with death.

 

 

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