Cholesterol, part 1: What is it?

 

Despite getting a bad rap for the past 70 years, cholesterol is essential for life.  Without cholesterol, we could not survive.  So, how did this vital substance get labeled as villain?

Mainstream health care has perpetuated the myth that there is “good” cholesterol and “bad” cholesterol, but it’s just not that simple.  The majority of physicians and other health care professionals have been trained to treat cholesterol in that overly simplistic manner and continue to do so without questioning the conventional belief, basically confirming that they haven’t read a medical journal within the last 20 years.

Let’s cut to the chase: Your health is not defined by one number.  Understanding the relevance of cholesterol requires an understanding of one’s overall metabolic health.

 

What is cholesterol?

Cholesterol is a waxy substance that was first recognized as a component of gallstones in 1769.  It was then isolated from animal fats in 1815 by the French chemist Chevreul.  The structure of cholesterol was fully defined in 1927 by the German chemist Heinrich Wieland, for which he was awarded the Nobel Prize.

Cholesterol is carried by lipoproteins

Since cholesterol is insoluble in water (and blood), it is carried by protein structures called lipoproteins.  Lipoproteins vary in size and density, and they are differentiated by the proportion of their components.  These lipoproteins contain primarily cholesterol and triglycerides. – from chylomicrons to high-density lipoprotein (HDL).

 

 

Approximately 7% of the total body’s cholesterol circulates in the plasma, mostly in the form of LDL.

 

How is cholesterol made?

Every cell in vertebrate organisms possesses the machinery both to synthesize cholesterol and to metabolize it.  Evidence suggests that this de novo synthesis is essential, no matter how much cholesterol is present in our diet, particularly in the brain.  The liver is the only organ that is good enough at making cholesterol that it can provide cholesterol to the rest of the body.

It’s estimated that 75% (800-1,200 mg) of our body’s cholesterol requirement is made by our body, and the remaining 25% (300-500 mg) must come from dietary intake.  For a 70-kg man, the total body stores of cholesterol equal roughly 70,000 mg (70 gm) (ref).

Of the cholesterol made by our body, up to 50% of it is made by the liver, while the remaining 50% is made by other cells (ref).  The body’s production of cholesterol adapts to our dietary intake, thereby maintaining a relatively stable level of total body cholesterol.

 

Even if one consumes no cholesterol at all, the human body will synthesize cholesterol.  The body can make cholesterol out of anything – fats, carbohydrates, or proteins.  It’s that important.

An example of how important cholesterol is to the body can be seen when looking at individuals who suffer from a genetic disorder that lacks an enzyme that is critical for cholesterol synthesis.  In Smith-Lemli-Opitz Syndrome (SLOS), the deficiency of 7-dehydrocholesterol reductase results in developmental delay, autism, and numerous physical anomalies (ref).

 

The Important Enzyme – HMG-CoA Reductase

I’ll spare you the details of how cholesterol is synthesized, a process that entails 30+ chemical reactions.  The most important part of that process is the 3^rd step – involving HMG-CoA Reductase.  HMG-CoA Reductase drives the commitment step in the production of cholesterol – once that step happens, cholesterol is getting made.

There are 2 factors that determine the activity of this enzyme:

• Cholesterol levels inside the cell
• Insulin levels in the blood

If the cholesterol level inside the cell were low, it would certainly make sense to produce more cholesterol for that cell.

When it comes to insulin, it’s important to realize that insulin is generally a signal for growth.  Insulin is released when glucose levels are high, which is an opportunity to “grow” our fat stores, for example.  In order for our body to grow, we need to produce more cholesterol for the newly formed cells, hence the increased activity of HMG-CoA Reductase.

You may recognize the name of that enzyme from the medications known as HMG-CoA Reductase Inhibitors, aka statins.  The enzyme is the target of the lipid-lowering statin medications that are the most widely used cholesterol medications in the world and have surpassed $1 trillion in sales.  That enzymatic step in the synthesis of cholesterol is indeed a big deal.