Demystifying Cholesterol

Cholesterol, an animal sterol, is a waxy substance found in every cell in our body. Cholesterol is used as a base for the production of steroid hormones, bile salts, and vitamin D as well as maintaining cell membrane fluidity. Without cholesterol we would not be able to properly digest foods, our cell structure would not be able to withstand any changes in temperature, and a significant number of important hormones such as estrogen, and testosterone could not be produced.

Our cholesterol is produced in the liver, from the molecule acetyl-coenzyme-A, through a number of complicated reactions that I won’t bore you with. A key step is a conversion that is controlled by the enzyme HMG-CoA (3-hydroxy-3-methyl-glutaryl-CoA) reductase. This enzyme can block the production of cholesterol making it an important target for cholesterol lowering drugs called statins, but it also controls the production of many other molecules such as co-enzyme-q10. That’s why there are so many side effects of taking these drugs. Nearly 10-12% of patients on statin drugs will experience statin induced muscle pain. Other potential adverse reactions to statin drug use include elevated liver enzymes, lung disease, and in a small subset of patients can even increase risk for Type 2 Diabetes Mellitus.

But back to cholesterol synthesis. The majority of cholesterol is synthesized, recycled, and degraded in the liver. So how does the water fearing cholesterol molecules that you eat get to the liver from the gut? And then how does it go from the liver to the cells if it cannot travel through the bloodstream alone?

Well, first cholesterol molecules are transported to the liver via the lymph in complexes called chylomicrons. When it gets to the liver it is repackaged and the cholesterol is “chaperoned” around the body by the lipoprotein complexes. There are a number of lipoprotein complexes, which are classified based on the ratio of proteins to fat and cholesterol. Think of these as cholesterol carriages, moving it all around the body. LDL takes the cholesterol to tissues and HDL brings cholesterol back to the liver when we have too much. Low density lipoproteins (LDL), very low density lipoproteins (vLDL) and chylomicrons all have very high fat and cholesterol content as compared with the protein rich high density lipoprotein (HDL). Once packaged into vLDL, the cholesterol enters circulation and some of the cholesterol is deposited to the tissues along with fatty acids. Once it drops the cholesterol off, the LDL complexes should be taken up by liver cells after attaching to the LDL receptor on their surface. Meanwhile, HDL scavenges blood vessels and tissues for free-form excess cholesterol. It then returns to the liver where cholesterol can be excreted through the bile or recycled.

Cholesterol and Cardiovascular Health

High cholesterol, triglycerides, LDL, and trans fats are linked to increased risk of cardiovascular events such as heart attacks and strokes. Cholesterol can build up due to increased production, increased consumption, or decreased excretion. The cause of the build-up as well as the form of cholesterol in the plasma is important when determining risk and treatment.

Genetic disorders can affect the LDL receptors in the surface of liver cells causing an increased amount of LDL in circulation. High LDL levels in circulation lead to an increased risk of cardiovascular events irrespective of diet and lifestyle in these patients. However, genetic causes affect a small percent of the population diagnosed with high cholesterol. The majority of cases in North America can be linked to diet and lifestyle.

Increased consumption of cholesterol rich foods result in increased levels of LDL in circulation. Excess LDL-C can attach onto and infiltrate the walls of blood vessels. When the LDL infiltrates it will form a reactive oxidative species that will attract immune cells. From the complexes formed, more white blood cells will congregate and an inflammatory cascade will be initiated. As more and more cells are attracted to this middle layer of a blood vessel, the plaque will begin to disrupt blood flow and may eventually fully block the vessel, or a piece of the plaque can rupture and travel around the body. All of these scenarios can have very serious consequences.

The “arthrogenic triad” are lab findings that show an increased risk for the development of atherosclerosis (or hardening of arteries) this includes high serum LDL, low HDL and high triglycerides. Risks are increased with low fiber diets as this prevents the excretion of cholesterol. A somewhat inactive lifestyle can also increase the risk of the LDL adhering to the vessels.