Taking on Cholesterol Part 1

Cholesterol and its connection with heart disease are controversial medical topics nowadays. While there is definitely a connection, I would argue (as you’ll see) that the conventional wisdom regarding cholesterol is not on point with the science. There’s far more to it than just the blanket statement “Cholesterol is Bad!”.

In this series (yes it’s going to be a series, this is a big topic) I’ll show you the following:

  • Why cholesterol is not bad for you
  • What is the best indicator of higher risk of heart disease
  • Why diet plays a major role in heart disease risk (and not in the way you think)
  • What you can do to lower your risk

So let’s roll!

Part 1: Cholesterol: What is it?

Cholesterol is a waxy substance that is very important for the function of the human body. We get some of it from our diet, but the majority of it comes from the cells of our body. Our cells manufacture it themselves to keep the level of cholesterol in your body at a constant level. In fact, the cholesterol you get from your diet has very little effect on your overall cholesterol levels.

What that means is the amount of cholesterol you get in your diet matters very little. The low cholesterol diets that have been publicized for years do not do much: the majority of the cholesterol we eat never gets absorbed.

In the body, cholesterol is used for a variety of functions:

  • to produce and maintain cell membranes (the outer walls of cells)
  • to build hormones and vitamins (including testosterone, estrogen, vitamin D, etc).
  • as a major building block in the structure of the brain (the brain contains 25% of all the cholesterol in your body)

An important point here: Cholesterol itself is not actually bad for you.

Cholesterol is truly vital for proper function of the human body. In fact, low cholesterol levels have been shown to lead to low levels of hormones like testosterone (cholesterol is a major building block in the synthesis of this and other hormones). Also, low levels have been linked to problems with brain function (such as depression, dementia, etc). David Perlmutter, MD does a great job of going through the role of cholesterol in the brain (in particular how important it is for good brain function) in his book Grain Brain and his website.

Even more interesting is the fact that lower total cholesterol levels have been correlated with increased risk of death from all causes. It has been suggested that high levels of total cholesterol are in fact protective, particularly in the elderly population.

What I’m trying to show here is that the blanket statement of all cholesterol is bad is a major oversimplification. Cholesterol is very important to our overall health and should not be looked at as something to be avoided. That’s not to say that “cholesterol” is good in every way either. The connection between cholesterol and heart disease is real, it’s just not quite as cut and dry as you may have been led to believe.

To delve deeper into this, I need to first go through how cholesterol is transported through the body: via particles called lipoproteins.

Lipoproteins are carriers of triglycerides (fats), phospholipids (cell membrane building blocks), and cholesterol. As these 3 types of molecules cannot dissolve in blood on their own, they need carriers. There are a few different kinds of lipoproteins, the most well-known are HDL (High Density Lipoprotein) and LDL (Low Density Lipoprotein). There are also chylomicrons, VLDL (Very Low Density Lipoprotein), and IDL (Intermediate Density Lipoprotein). You can think of all these lipoproteins as different shaped bubbles filled with fats and cholesterol. Note these are not cholesterol themselves, rather they are carriers of cholesterol.

The main role of these particles is this: the liver and intestine package and release VLDL and chylomicrons respectively. These lipoproteins flow through the bloodstream delivering fats (energy) and phospholipids to different tissues. As they shed these molecules, they become smaller and smaller. VLDL eventually shrinks to LDL while chylomicrons become chylomicron remnants. At this point, once they have delivered their cargo, the LDL/remnants return back to the liver/small intestine where the cholesterol in the particles is reused or excreted.

This is the normal function of cholesterol transportation (though HDL has a slightly different role as I’ll touch on later). The problem here comes when LDL particles move from the bloodstream into the walls of blood vessels (specifically the arteries). This causes the buildup of plaques in artery walls (atherosclerosis).

As these atherosclerotic plaques develop, they can grow up into the artery (blocking off circulation) or rupture (sending blood clots that can also block off circulation). This is how heart attacks and strokes occur.

This mechanism is why cholesterol, and specifically LDL, has been pointed out as the “cause” of heart disease, and why there is enormous push for drugs to treat “high cholesterol levels”. In fact, treating and preventing high cholesterol is a major part of what many physicians do on a daily basis.

Note: LDL has come to be known as “bad cholesterol” though it is not actually cholesterol itself, rather it’s a lipoprotein as we discussed above.

Let’s look real quick at what physicians are looking at when they evaluate a person’s cholesterol levels. These are the readings you would see when you have your “cholesterol” levels (known as a Lipid Panel) tested at your doctor’s office.

  • Total Cholesterol (TC) – this is a measure of the total amount of cholesterol in your blood contained in all the various lipoproteins listed above
  • LDL-Cholesterol (LDL-C) – this is a measure of the amount of cholesterol contained in all the LDL particles in the body
  • HDL-Cholesterol (HDL-C) – this is a measure of the amount of cholesterol contained in all the HDL particles in the body (HDL is often referred to as good cholesterol)
  • Triglycerides (TG) – this is a measure of the amount of fat molecules contained in all the various lipoproteins (this one is important as we’ll get to later on)

The big task for physicians is to try to tell from these lab values who is at risk for developing atherosclerosis and therefore heart disease. In general, physicians look at LDL-C levels (and total cholesterol to an extent) to determine who is at the highest risk and thus who to treat with cholesterol lowering medications (usually statins).

There is an issue with using these specific lab values, however. These values are not good at predicting who is going to have a heart attack.

Studies have shown that, in fact, the majority of people who get hospitalized for Acute Coronary Syndrome (heart disease) actually have good LDL-C levels.

The way patients are currently being treated assumes that those most likely to suffer heart attacks are the ones with the highest LDL-C levels. This is obviously not the case.

So what is going on?

At this point, I want to direct you to the impressive analysis written by Peter Attia, MD on his blog. He takes an extensive in-depth look at the different variables measured on the lipid panel and their connection with heart disease risk. If you want to learn more than you probably would ever want to know about cholesterol, I would definitely recommend checking out his entire Straight Dope on Cholesterol series.

To summarize greatly, the one factor that matters here in overall risk of heart disease is the number of LDL particles in the bloodstream. Total cholesterol, and even LDL-cholesterol level (tested in the lipid panel as noted above) do not accurately predict risk of heart disease nearly as accurately.

Important: LDL Particle Number is different than the LDL-Cholesterol measured in the lipid panel. The reading you get from your lipid panel is a calculated estimate of cholesterol contained in LDL molecules. One, this is not an actual measurement as it is only an estimate (only TC, TG, and HDL-C are directly measured). Two, it does not say anything about the number of actual LDL particles there are.

Think of cholesterol molecules as people and LDL particles as the cars they drive in. Measuring LDL cholesterol is like measuring the number of people in all the cars on a highway, while measuring LDL particle number is measuring the number of cars.

It is the number of molecules, not the amount of cholesterol contained in them, that is directly correlated with risk of heart disease. What matters is the number of cars (LDL particles), not the number of people in them (cholesterol).

This difference between measurements would not be a big deal if LDL particle number and LDL cholesterol levels matched all the time or even a majority of the time. Unfortunately, this is not the case.

To illustrate: say you have 5 people traveling on a highway. They could all be riding in one car or they could be all driving separate cars (therefore there would be 5 cars). There is no way you can tell how many cars there are just by counting the number of people travelling. The same thing can happen with LDL particles and cholesterol.

In the end, what you want is fewer cars (LDL particles), the number of people (cholesterol) traveling doesn’t matter. Unfortunately, the only way to tell how any particles there are is by directly measuring it. This can be done with specialized lab tests.

To summarize the issue here: just because your cholesterol numbers your doctor checks are “good” doesn’t necessarily mean you are not at high risk for a heart attack.

This is a very important point, as physicians often choose which patients to treat based off the LDL-cholesterol levels, not realizing that it is in fact the LDL particle number that matters. It is not their fault as even the expert panels who put out guidelines still recommend this. However the science is quite clear (again for a more depth explanation check out Peter Attia’s blog).

So where does this leave us? Let me summarize a couple key points first.

  • Cholesterol itself is not bad for you, it is a vital part of our body, especially for hormone production and brain health as well as overall cellular health
  • Risk of heart disease is directly related to the number of LDL particles floating around in the bloodstream. This is not measured on a normal blood lipid panel.

In Part 2 I address the following:

  • What causes someone to have a high LDL-particle number
  • What else you can tell from your lipid panel
  • What to do to lower your risk of heart disease

 

About the Author

Chris Goodrich, MD

3 Comments on “Taking on Cholesterol Part 1”

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