Below is a correspondence between Dr. Cordain and Luke Milano regarding Innuit mummies and Cardiovascular disease:
Hi Professor Cordain:
I listened to your interview with Jimmy Moore where you discussed the results of 2 Innuit mummies examined by the researcher from Pennsylvania. If I’m understanding you correctly, you acknowledge that high fat intake may have contributed to the arterial plaque but there was no evidence of heart attack. You stated that inflamation is necessary for rupture of the fibrous cap that precipitates the heart attack.
The whole subject of plaque, rupture, inflamation and saturated fat and their relationship to each other is a hot topic of discussion but no one that I know of has truly presented a thorough analysis. Perhaps this would present an opportunity for you to be the one to pull the proverbial sword out of the stone.
First point of clarification. Damage to the endothelial lining is the start of the process. It is my understanding that inflamation is either necessary or is a key factor in this regard. Your interview was not specific as to what role inflamation played in initial damage to the endothelial lining. Secondly, those who oppose saturated fat consumption argue that it is the “flat” molecular structure of saturated fats that contribute to plaque formation, as these flat molecules lay down more easily to cover the damaged areas of the endothelial lining. ( As opposed to unsaturated fats which have a “bent” or “kinky” molecular structure )
Then there is the issue of foam cells. It has been argued that macrophages consume the LDL along the endothelial lining. However macrophages do not have a built in governor to prevent them from overconsumption of LDL and once they are “maxed out” they become foam cells, and it is these foam cells that consitute the arterial plaque. Built into this process is calcium incorporated in the plaque representing 20% of the volume which brings about the “hardening” of the arteries. However it has been argued that the calcium content is functional and purposeful as it provides “structure” to the plaque and hence diminishs the chance of rupture.
But it has been argued that it is cholesterol that is the “spackle” so to speak that is used to repair damage to the endothelial lining. Cholesterol is delivered by the VLDL in the bloodstream ( more correctly cholesterol esters )
So these are the questions that need clarification. Is inflamation necessary for damage to the endothelial lining? WIll saturated fat ( flat molecule ), LDL or cholesterol cause damage to the endothelial lining merely by its presence in greater volume? What is the role of saturated fat ( flat molecule ) in relation to creation of cholesterol or LDL? It would seem that the “flat molecule” theory is a moot point as cholesterol and LDL have their own molecular makeup. Do foam cell cadavers, so to speak, create the spackle to repair the breaks in the endothelial lining and come to consitute the bulk of arterial plaque?
One example would be high blood pressure. The higher pressure creates friction along the sides of the blood vesseel ( endothelial lining ) and results in small breaks, fissures, etc. How are these breaks sealed? By flat moleculed saturated fat in the bloodstream? By LDL? By macrophage? Can repair be made without the macrophage forming foam cells? What is the role of calcium in this process? This is a topic worthy of discussion because proponents of chelation therapy argue that chelation can reduce the calcium content of plaque. Even if this is physiologically possible, reduction may have short term benefits to patients because it reduces plaque volume but is hazardous long term because greater chance of rupture is created from the calcium loss.
Granted, this email is convoluted. Almost by necessity, important initial questions in unexplored areas tend to be convoluted. But my questions address issues that have not been clearly and fully addressed by the scientific community. I have long admired your work and believe that you perhaps better than anyone else can bring clarity to these questions.
Dr. Cordain’s Response:
Thank you for your interest in my work and how contemporary Paleo diets may slow or prevent atherosclerosis. This process is still incompletely understood because of the complex interaction of a variety of environmental and genetic factors. Nevertheless, the etiology of the disease is like a jigsaw puzzle and we (humanity) has placed together many of the outside pieces and much of the interior — yet key pieces still remain to be discovered and how they influence the overall process. My feeling is that no single sivler bullet exists to prevent atherosclerosis, however we can take many behavioral steps (diet/exercise/no smoking/stress reduction) to put the odds on our side. Hence, a modern day Paleo diet is one of the most powerful behavioral aspects of slowing or preventing atherosclerosis.
If you scour MEDLINE (//www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed) for review articles on the topic, many of your questions can be answered. However, let it be known that a complete consensus still does not exist as to how a variety of dietary/environmental factors may promote or inhibit atherosclerosis. Let me briefly answer the questions you have listed below:
“So these are the questions that need clarification. Is inflamation necessary for damage to the endothelial lining?”
First off, endothelial cells in arteries do not represent the structure which normally comes in contact with either red blood cells, white blood cells, platelets or other formed elements in the bloodstream. The interface is actually a structure called the glycocalyx which is thicker and contains more mass than the single cell endothelium. The glycocalyx is a filamentous (hairy) structure composed of carbohydrates that are anchored to the endothelium and serves as a physical barrier to prevent any formed element (red blood cells, white blood cells, platelets etc) from coming in direct contact with the endothelium. When blood flows in the artery, the glycocalyx lays down like your hair in a shower and prevents cells or large molecules access to space (the intima) below the endothelial cells. Hence, one of the very first steps in atherosclerosis is the shedding of the glycocalyx to expose the endothelial cells to the bloodstream. Inflammation appears to be a key process underlying the shedding of the glycocalyx. Another key step to this process comes from where atherosclerosis occurs along arteries. It almost never occurs in areas of laminar blood flow, but in areas where arteries branch or bifurcate and turbulent blood flow occurs. It is likely that the glycocalyx is more easily shed or disturbed in these areas.
” Will saturated fat ( flat molecule ), LDL or cholesterol cause damage to the endothelial lining merely by its presence in greater volume?”
Saturated fatty acids (the most common dietary sources are 12:0, 14:0, 16:0 and 18:0) actually are not flat, but form a zig, zag linear structure like a saw blade with 109 degree angles between the single bonds (or toothes of the saw blade). Saturated fatty acids are insoluble in water (If you put salad oil in a glass of water it forms beads). So to transport fatty acids in water (the bloodstream), our bodies attach them to proteins. LDL (low density lipoprotein) are complexes of protein, fatty acids and cholesterol which deposit fatty acids (saturated fatty acids and others) and cholesterol in cells. LDL molecules come in two basic forms: 1) small dense LDL and 2) fluffy LDL. When the blood concentration of LDL increases, as what occurs when we eat lots of saturated fats, the LDL molecules migrate from the bloodstream into the space below the endothelial cells called the intima. Small dense LDL tend to remain in this space much longer than fluffy LDL and become oxidized (rancid). Oxidized LDL cause inflamation, glycocalxy shedding and damage to the endothelial lining. Once the glycocalyx is shed, then white blood cells in the bloodstream can enter the intima by attaching to adhesion molecules (ICAM, VCAM) attached to endothelial cells. This process causes further inflammation which accelerates this process. Once inside the intima white blood cells (monocytes) are converted to macrophages (the garbage truck cells of the body) which gobble up oxidized LDL molecules. Because macrophages contain a special receptor for oxidized LDL (the scavenger receptor), the continue to gobble up oxidized LDL and are transformed into foam cells which form the beginning of the plaque which blocks the artery which results in atherosclersis. Clearly, any dietary factor which promotes inflammation, or the formation of small dense LDL accelerates this process. I believe that many elements in the typical western diet (trnas fats, high glycemic load carbs, grains, legumes, and dietary elements that cause a “leaky gut”) contribute to this process. Under the context of a modern day “Paleo” diet, LDL is frequently elevated, but it generally is the fluffy LDL and along with this, HDL (the good cholesterol that reduces atherosclerosis) is elevated while triglycerides are reduced. The net effect is that this blood profile reduces the risk for heart disease and atherosclerosis.
“What is the role of saturated fat ( flat molecule ) in relation to creation of cholesterol or LDL? It would seem that the “flat molecule” theory is a moot point as cholesterol and LDL have their own molecular makeup. Do foam cell cadavers, so to speak, create the spackle to repair the breaks in the endothelial lining and come to consitute the bulk of arterial plaque?”
I have pretyy much answered this question in the paragraph above. Saturated fats elevate blood LDL but generally it is the fluffy LDL, but they simultaneously elevate HDL and reduce triglycerides thereby having either no adverse effects or a slight positive effect on blood lipids — all other dietary variables being the same. Foam cells result from macrophages that have accumulated excessive LDL molecule constitutents such as cholesterol and saturated fatty acids. Foam cells are “walled over” by connective tissue, calcium and smooth muscle cells, and this process forms the plaque which blocks the artery. The outer hard part of the plaque is called the fibrous cap and normally isolates the plaque from the bloodstream. When the fibrous plaque ruptures, it causes a blood clot which can result in a heart attack (if the clot occurs in a coronary artery supplying the heart) or a stroke (if the clot occurs in an artery supplying the brain). Inflammation is intimately tied to the processes that cause a rupturing of the fibrous plaque. The same dietary factors that cause chronic low level inflammation resulting in a shed glycocalyx also participate in rupturing of the fibrous cap. Interestingly, a substance in wheat called wheat germ agglutinin (WGA) may promote rupturing of the fibrous cap by upregulating enzymes known as metalloproteinases (MMP2 and MMP9). WGA may also promote the artery clotting process by encouraging plateletes to stick to one another.
So contemporary diets which mimic the nutritional characteristics of our ancestors may be one of the best strategies you can take to prevent atherosclerosis.
Loren Cordain, Ph.D., Professor Emeritus