Friday, February 10, 2012

The Cholesterol Carriers (Part 2)

In our last post, we discussed the origin of the cholesterol myth and how the early research on cholesterol and fat intake was so flawed as to be meaningless. In this post, we will look at what we now understand actually causes heart disease. So if eating fat and cholesterol does not cause heart disease, then how exactly is cholesterol involved in heart disease?

WHAT IS CHOLESTEROL, WHERE DOES IT COME FROM, and WHY DOES IT MATTER?

First and foremost, cholesterol is absolutely essential to your body functioning properly. Cholesterol is used to make hormones, forms the membranes of most cells, and is required for the purposes of digesting and absorbing many nutrients from food. You wouldn’t be able to make new cells or repair damaged ones without cholesterol. For this reason, your body actually manufactures its own cholesterol. We simply cannot live without it.

While it is absolutely correct to say that when you eat food that contains cholesterol, some of it gets absorbed through digestion, it is a misleading over-simplification. Yes, you do absorb some of the cholesterol from food, but your body makes the vast majority of cholesterol it needs and uses. In fact, there is a mechanism which closely regulates the levels of cholesterol in your body. If you eat a meal rich in cholesterol, your body simply lowers its production to maintain its own “normal” level. If you eat foods which contain very little cholesterol, your body just makes more. The “normal” level is determined primarily by genetic factors, but there are some changes to your body through your life can alter levels of the different types of cholesterol.

LIPOPROTEINS (LDL, HDL and VLDL) - THE CHOLESTEROL CARRIERS

As you know, oil and water don’t mix easily, a problem if you are trying to move a fatty substance, like cholesterol through a watery substance (blood). Lipoproteins solve this problem by transporting cholesterol as a water soluble packet through the blood stream. So a lipoprotein is basically a protein structure that surrounds fat and cholesterol molecules and makes them water soluble.


Cholesterol is basically a waxy steroid form of fat. Since it is hydrophobic (repels water), it can make up cell membranes which surrounds and protects every cell. In order for cholesterol to move around your body through your blood stream, it must become water soluble. Your body basically packages cholesterol inside these specific proteins to make molecules called “lipoproteins” (“lipo” meaning fat and “protein” of course meaning protein).

These lipoproteins transport cholesterol to cells that need it or transport cholesterol from cells back to the liver. In and of themselves, lipoproteins are not inherently bad or good because every lipoprotein is absolutely necessary for our bodies to function properly.

So let’s look at what these lipoproteins do in the body:

  • High-density lipoproteins (HDL), sometimes referred to as the "good cholesterol" lipoprotein, collects cholesterol from the body's tissues, and bring it back to the liver. High levels of HDL allows your body to better collect cholesterol and return it to the liver where it can be reused or excreted as bile. If you need to get rid of extra cholesterol (as in patients with congenital hypercholesterolemia - a genetic predisposition to excessively high levels of cholesterol), this is extremely important.  
  • Low-density lipoproteins (LDL), sometimes referred to as the "bad cholesterol" lipoprotein, carry cholesterol from the liver to cells of the body to be used in many important body processes. Certain types of LDL can get “stuck” in the arteries and then come into contact with free radicals, which leads to damage, inflammation, and a buildup of plaque. There are a couple different kinds of LDL which we will discuss this more later on.
  • Very-low-density lipoproteins (VLDL) carry newly synthesised triacylglycerol (the building blocks of fat also known as triglycerides) from your liver to your adipose (fat) tissue. Doctors usually test for triglyceride levels in blood tests. VLDL molecules are much larger than the other types of LDL, so they don’t get stuck in the arteries.

So why is LDL labeled the “bad cholesterol”? Since LDL performs a critical function in the body, you may wonder why it has been labeled as “bad”? After all, your cell membranes (including your brain cell membranes) cannot be created or repair themselves without LDL carrying much needed cholesterol throughout your body?

It has become very confusing because doctors and the media tend to think of LDL as cholesterol itself. Rather, as we have discussed, LDL is not cholesterol but a protein structure created to carry cholesterol. As you know, high levels of LDL are touted as one of the most accurate predictors of cardiovascular trouble. Is this true? Well it seems odd that when you look at the research done on correlating heart disease and LDL that half of all people who suffer heart attacks actually have average blood levels of LDL. How can this be if cholesterol is the insidious culprit it has been made out to be?

FREE RADICALS - THE TRUE CULPRIT

When people talk about how “cholesterol is bad”, what they really mean to say is that oxidized LDL is bad. Then again, there are a great many things in your body that, when oxidized, are bad. So it is the oxidative damage, rather than the LDL that is bad right? Well, here’s where it gets tricky. LDL doesn’t usually get oxidized unless it gets “stuck” somewhere in the artery wall. So how does LDL get stuck in the first place?

LDL SIZE

It turns out that the not all LDL cholesterol is the same. Part of reason for so much confusion is that until recently, there has not been a reliable way to determine the size of LDL molecules (commonly called “particle size”). More recently, several tests have been developed which can now differentiate the sizes of LDL molecules. Once researchers started measuring the particle size of LDL they realized that only the very smallest sized LDL actually has anything to do with heart disease.


LDL comes in many sizes, but only the smallest
(LDL type B) is responsible for coronary artery damage.


We now know that LDL comes in various sizes, and that it’s the LDL “type B” that can be dangerous. When these type B LDL molecules travel through the blood stream they can get stuck in spaces between the endothelial cells that line arteries (these spaces are called “gap junctions”) These spaces are there to allow nutrients to travel out of the blood stream to nourish the arteries themselves. When type B LDL gets stuck in these spaces, they have the potential to get oxidized by any free radicals floating by in the blood stream. If an LDL molecule cannot get stuck in the endothelial wall (because it is too big) then it does not get oxidized. So the only kind of LDL that really matters to heart disease is the very small type B LDL particles. Unfortunately, blood tests for cholesterol only measure the total LDL in blood, without regard to type A or type B, so basing “high cholesterol” off of this measurement is misleading, to say the least.

So what researchers have come to understand is that it is this type B LDL, when combined with free radicals, are the true culprit in the development of atherosclerosis and eventually heart disease. A big part of heart disease really isn’t how much total LDL cholesterol you have in your blood stream, but rather whether you have a high level of LDL type B and also have too many free radicals that are not being neutralized by antioxidants.

In our next post we are going to explain how this free radical - type B LDL combination leads to a cascade of inflammatory events that eventually leads to narrowing of the coronary arteries and heart disease.

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Researched and written by Dr. Rebecca Malamed, M.D. with assistance from Mr. Malcolm Potter.

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