Q&A: Innuit Mummies and Cardiovascular Disease

Dr. Cordain's Response:

Hi Luke,

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 silver 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 inflammation 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 constitute the bulk of arterial plaque?"

I have pretty 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.

Cordially,

Loren Cordain, Ph.D., Professor Emeritus