Is It Cholesterol or Is It Oxygen?

I am virtually a vegetarian. (I eat pizza, which has milk, and had a meatball in New York last summer). However, my cholesterol is high, and I take cholesterol-lowering medication. Cholesterol comes from the animal family, and I eat virtually no animal products, so why would my cholesterol be high?

Approximately 75% of our cholesterol comes from what our liver produces, NOT from what we eat.   An enzyme called the HMG-CoA reductase is used by the liver to create cholesterol.  Medications called statins, which act on this enzyme, can lower one's cholesterol by up to 60%.   By contrast, medications that block cholesterol absorption from our diet will only lower cholesterol approximately 10%.

What exactly is cholesterol, and why, for many of us, does the liver produce so much of it?

To understand cholesterol, we must go back to basic biology and discuss prokaryotes and eukaryotes. Prokaryotes are cellular organisms whose cells do not have a nucleus, and eukaryotes are cellular organisms whose cells have a nucleus and other membrane-bound organelles. Prokaryotes do not have cholesterol, while eukaryotes use cholesterol to form the nucleus and other membrane-bound organelles. The cholesterol allows a stiffness and organization to the cellular membranes. The cholesterol also acts as a means of intracellular transport within the membrane itself. We humans, as well as all mammalians, are eukaryotes. 

Konrad Emil Bloch received the Nobel Prize for Medicine for his work on the biological synthesis of cholesterol in 1964. He noted that the creation of cholesterol required a great deal of energy and oxygen. The creation of cholesterol requires approximately 27 separate processes. He hypothesized that the utilization of oxygen to create cell walls and cholesterol walls was a complex organism's response to an oxygen-rich environment.  From this theory, we understand that cholesterol formation is an ingenious process of using the oxygen for the organism's benefit.

As we age, this cholesterol production can contribute to atherosclerosis through the process of developing an atheroma, or an intracellular lipid accumulation. Here is a nice picture of it from Wikipedia.

Cholesterol is insoluble in water and requires lipoproteins to transport it. Low Density Lipoproteins (LDL) deposit the cholesterol in plaques inside the arterial walls, while High Density Lipoproteins (HDL) act like scavengers and can help remove some of the plaques. The amount of LDL in the human organism is strongly related to cardiovascular risk.

However, it was discovered that it was not just LDL, but the degree of oxidized LDL that correlated with endovascular injury.  Oxidized LDL can damage the endothelial cells and allow cholesterol to build deposits in the subendothelial area (the space right below the endothelium lining the artery). This injury to the endothelial lining allows more cholesterol deposits to be created in the subendothelial area, creating more inflammation. White blood cells known as macrophages, which fight inflammation, try to repair the injury caused by oxidized LDL and consume them, causing “foamy macrophages.” This process is a very aggressive, angry, inflammatory process. If any of the area ruptures, then a blood clot can be formed, as stated in the prior post on coronary artery disease.

This process is known as “oxidative stress.” It is like rust on the bottom of an old car. Oxygen can be a very hungry molecule and has the ability to rip electrons off other nearby molecules. The molecules with the missing electrons are known as free radicals, and they can rip electrons off other nearby molecules, causing a free radical chain reaction.  As ferric oxide eats away at a car, so can this oxidative injury damage the endothelial lining of our cell walls.

As scientists understand more about this inflammatory, aggressive process, more unique treatments are being discovered. For instance, although powerful antioxidants such as Vitamin E and Vitamin C were not necessarily found to be beneficial for decreasing heart disease, other types called polyphenol antioxidants may be quite effective. In fact, in a study in the Journal of Clinical Nutrition, the use of pomegranate juice (a polyphenolic antioxidant) actually reduced atherosclerotic plaque in individuals with carotid artery stenosis. In a study in the journal Atherosclerosis, the addition of pomegranate extract to statins actually reduced macrophage foam cell formation and was felt to potentially decrease atherogenesis.

In short, cholesterol itself is amazing. It plays an essential role in the membranes of animal cell walls. It also is critical in the formation of molecules such as Vitamin D, steroid hormones and bile acids. But it appears intimately associated with oxygen.  Cholesterol may be created as a response to an oxygen-rich environment, and oxidative stress can impact the LDL receptors that carry it and contribute to the creation of atherosclerotic disease.  Perhaps in the future, we may become wiser about various lifestyles that may optimize the benefit of both oxygen and cholesterol without creating a disease process from them.