Chris Kresser: There are several causes as you know and as you all will find out more about us when we get to the cholesterol unit and blood chemistry section. There are many different causes of hypercholesterolemia, but two of the primary causes are insulin-leptin resistance and metabolic disturbance and genetics. When someone has insulin and leptin resistance as a cause of high LDL particle number, here’s what’s going on: they will have higher triglyceride levels and lipoproteins like low-density lipoprotein or LDL, and they carry triglycerides as well as. Cholesterol and fat-soluble vitamins and if triglycerides are high, that means the lipoprotein will be relatively full of triglyceride, and they’ll have less room leftover to carry the equivalent amount of cholesterol around the body, which is an important service that they provide. The liver will have to manufacture more lipoproteins in order to carry the same amount of cholesterol given a higher triglyceride number. That’s how elevated insulin and leptin resistance will increase LDL particle number. However, another potential cause of high LDL particle number is genetics. If people have genetic polymorphisms that lead to reduced LDL receptor sensitivity, the LDL receptor sits on the outside of the cell, and its job is to take the LDL particles out of the circulation and pull them into the cell. If those receptors are not expressed properly or not sensitive enough because of genetic polymorphisms, then you’ll get a higher number of LDL particles circulating around the blood, or you could have an APO B mutation. APO B is the protein on the outside of the LDL particle that is supposed to dock with the LDL receptor. If you have a mutation of polymorphism in that protein, then that can lead to high LDL particle number. We’re going to talk a lot more about this later, but those differences in the cause inform the different diets. Usually, people with genetic polymorphisms that lead to high LDL particle number are sensitive to the effects of dietary saturated fat and possibly cholesterol itself, and so those people tend to do better on moderate carbohydrate—moderate fat but lower saturated fat, moderate protein type of diet, whereas people with insulin resistance tend to do better on a lower carb diet, which would address the metabolic problems. I hope that’s clear from now on. We’re going to be covering in much more detail later.