Cholesterol Lipid Hypothesis Part III
March 6th, 2023
So far, I have put forth some hypotheses that are controversial and raise questions about the American College of Cardiology guidelines. This is fine with me because this is about stimulating a conversation about disease etiology and treatment. Readers are never encouraged to go against their physician's recommendations. The choice to change a current therapeutic regimen is solely between the patient and their provider and frankly is likely predicated on how much damage has occurred over one's current lifetime coupled with genetic risk and the ability to alter lifestyle risk factors effectively.
I believe that pharmacotherapy, i.e. statin drugs, are necessary for patients who are unwilling to pursue aggressive lifestyle changes, have significant genetic risk factors, don't respond well to herbal therapies or have advanced coronary artery disease requiring medication therapy. However, I do encourage every person to look at the science, to be informed and then discuss with their physician the possibility of non-pharmacologic therapy with or without drug treatments where possible. This has two benefits: 1) decrease dose of drug, if taken, for effect needed 2) needing no drug at all.
I think that this point is critical! We as a culture need to be proactive in reducing risk by making significant lifestyle changes that are pro longevity, anti inflammation and stagnation. This will significantly reduce the need for medicine and reduce morbidity and mortality. Let us look at type 2 diabetes, one of the greatest risk factors for coronary artery disease, as an example. Whereas, type 1 diabetes is an irreversible loss of pancreatic insulin production because of autoimmune destruction of the insulin producing islet cells, type 2 diabetes is completely preventable and reversible! Type 2 diabetes is an inflammatory based insulin receptor problem that is acquired over years of poor quality Standard American diet choices coupled with sedentary behavior and toxin exposure. It is reversible by completely overhauling your diet, avoiding toxicants and exercising daily. The fact that we give humans insulin for type 2 diabetes speaks to the reality that we as culture are more wedded to eating what we like and want versus what makes us healthy. We are not doing a great job as a society of reducing our exposure to air, water and food based toxins that affect our risk. We are not doing a good job of reducing our stress levels. We are not doing a great job of exercising and walking enough for insulin resistance prevention.
Back to the cardiology story: The blockbuster statin drug's benefits are likely related to pleotropic effects and not solely on blocking the cholesterol synthesis enzyme HMG coA reductase. There is significant emerging data to support this notion. For example, atorvastatin has the ability to reverse lipid immune signaling defects that are present in systemic lupus patients and are thought to drive autoimmunity. Again, I believe that coronary artery disease is an infectious inflammatory mediated disease of the artery wall which would make sense as this data mechanistically emerges. (Jury et. al. 2006)
I believe that we have settled on the fact that cholesterol is not inherently bad unless unbalanced and that it clearly has a beneficial role in human health, we need to understand what really causes coronary artery disease. Dr. Mark Houston has written extensively on this topic and is a specialist in non-pharmacologic management of heart disease. Since it is my stated goal to aggressively pursue non-pharmacologic management if possible, especially at the youngest ages, he is my go to source for information.
As stated earlier, coronary artery disease is caused by endothelial dysfunction which precedes arteriosclerosis and atherosclerosis that we call a narrowed heart artery. This narrowed artery eventually has a plaque that ruptures causing rapid vessel closure that is called a heart attack or myocardial infarction, MI for short. Let's try and imagine this event in our minds.
Physiologically, an artery is made up of a sheet of cells that are organized in interlocking rows that form the endothelium of a long tube for blood to flow through. This is straight forward plumbing. Under normal homeostatic conditions, this tube is repaired constantly for blood to flow undisturbed forever. However, under stress from unbalanced mechanical and chemical forces, these cells will become dysfunctional, called endothelial dysfunction. Mechanical stress occurs with high blood pressure. Chemical stress occurs primarily through genetic risk factors, toxin exposure and poor-quality diets. (Houston M 2014)
For the sake of this discussion, I am going to focus on the chemical stressors as the mechanical stressors will be reduced by the same treatments that reduce the chemical stress.
The major causes of chemical stress on the coronary artery are: 1) unbalanced macronutrients - fats, carbohydrates and proteins, 2) unbalanced micronutrients - minerals primarily, 3) host genetics, 4) dysfunctional intestinal microbiota, 5) toxins. There are over 395 other causes, however, these are the big 5 that account for a large part of the disease.
Let us look primarily at inflammation and oxidative stress as they are two of the most damaging events occurring in the heart and the rest of the body primarily due to poor dietary choices, but also from exposure to drugs, chemicals, excessive exercise, excessive sun exposure and smoking. Oxidative stress is basically the event that occurs in the body when naturally beneficial oxygen radicals are overproduced.
These oxygen radicals are naturally produced by our cells to clear infections or during mitochondrial energy production activity. These radicalized molecules have unpaired electrons that are in a mad search for another electron to balance their sensibilities. When free and radical, they can destroy a bacterial or viral cell wall via this unpaired electron. When we have a pathogen to kill, this is good. What is not good is when they run into our liver cell or heart cell first. This damage, when it occurs to our cell wall and enzymes has a catastrophic effect if it occurs in high frequency. This is one of the major pathways to endothelial dysfunction and ultimately heart disease. (Slauch JM 2011)
If for example, you consume too much mercury via excessive consumption of tuna and you smoke cigarettes, you can start this cascade of reactive oxygen species that cause inflammation and cellular damage to the artery wall. Now let us say that hypothetically, you have a genetic predisposition for small and dense lipoprotein cars called LDL cholesterol that stay in circulation longer than normal because a gain of function PCSK9 SNP mutation and also have apolipoprotein E3/4 genotype which reduces clearance of the lipoprotein cars further while concomitantly consuming a high refined carbohydrate diet that promotes inflammation and oxidation, then you have the ripe condition for the small dense LDL particle to squeeze between a damaged endothelium of the artery wall cells because of a concentration gradient. These LDL particles can become oxidized by local oxygen radicals making them a target for the immune system to be engulfed by a macrophage cell thus beginning the process of atherosclerosis. Over a long period of time, many decades this pattern repeats itself over and over again until a fibrous plaque forms over top in order to protect the vessel wall. If this plaque gets big enough and ruptures, it can go two ways: 1) it can develop a healing clot that blocks the heart's blood flow leading to a lack of oxygen being delivered to the heart muscle effectively damaging the section involved or 2) if it is a smaller clot, it can heal over without blocking the blood flow. In an interview with Dr. Peter Attia, Preventative Cardiologist Dr. Ethan Weiss, stated that these events occur many times leaving pathological evidence like tree rings.
We further know that artery wall plaques that can cause a heart attack have walled off bacterial biofilms that come from our oral and gut bacteria. These bacteria have translocated to the heart and walled themselves off causing a local artery inflammatory process that is also ground zero for a potential heart attack. (Lanter et. al. 2014)
Since prevention is about catching disease where it begins, this is a conversation that parents need to have with their children.
Next week we will discuss the process from beginning to end of a plaque formation.
Jury J of Immunology Article
Slauch Molecular Microbiology Article
Houston World J of Cardiology Article
Cheng Critical Care Medicine Article
Lanter mBio Article