Do you know someone who works really hard but never seems to get the appreciation they deserve?
But I’m not talking about a person, I’m talking about cholesterol. This molecule that’s essential for human life is continuously looked down upon and used to scare people about heart disease.
That ends today, at least for you and me. This guide might be a bit lengthy, but it breaks down everything you need to know about cholesterol as simply as possible.
What is Cholesterol?
Cholesterol has gotten a bad rap, demonized in tandem with saturated fat.
Cholesterol is just a lipid molecule, which you can see below:
Note that LDL and HDL are not cholesterol…we’ll be getting to those in a minute.
Cholesterol happens to play a big role in many important processes:
- It is used to build and maintain all (animal) cell membranes
- Needed to produce steroid hormones (like testosterone)
- Needed to produce bile acid (important for a variety of processes, including small intestine function)
We couldn’t live without cholesterol…it’s a good thing.
But there is one situation where cholesterol can play a major role in cardiovascular disease. In order to properly understand that, there are a few more things you need to understand.
Is the Cholesterol in Your Eggs Killing You?
Cholesterol comes from 2 sources, and only 2 sources.
It is either synthesized in the body, or consumed as part of food (like eggs).
Having really high cholesterol levels is typically a bad thing (we’ll dive into that deeper soon). This has been understood for a long time, and is the reason that the nutrition guidelines of many Western countries advised against consuming foods containing cholesterol.
The problem with this is that there is a very poor (possibly non-existent) correlation between dietary cholesterol and serum cholesterol (1).
One of the reasons for that is that most of the cholesterol in food (over half) is esterified cholesterol. This is a form of the molecule that can’t be used by cells. While it can be converted to the active form of cholesterol, most of it is simply excreted by the gut.
Second, since cholesterol is so important to all cells, it is closely regulated. If cholesterol comes in through food, the body simply synthesizes less of it. Keep in mind that you would have to eat an obscene amount of cholesterol to come close to the amount that your body regularly produces.
In summary, dietary cholesterol has little significance on the cholesterol in your body (2). However, don’t mistake this for meaning that the food you eat has no effect on your cholesterol levels – as we’ll see later, it does!
While most countries have updated their nutritional guidelines to reflect this, the United States is just getting around to stating that “cholesterol is not considered a nutrient of concern for overconsumption.”
HDL and LDL are NOT Cholesterol!
A very common misconception is that HDL and LDL are types of cholesterol…not quite.
It’s completely understandable, as most test results come back labeled LDL cholesterol and HDL cholesterol.
But high-density lipoprotein (HDL) and low-density lipoprotein (LDL) are lipoproteins. They transport cholesterol, but are not cholesterol themselves. It’s a small distinction, but one you should be aware of.
What’s a Lipoprotein? (The Short Version)
A lipoprotein is a combination of lipids and proteins (lipid-protein, get it?). Structurally, it almost looks like a sphere.
Take a look at this drawing of an LDL (a low-density lipoprotein) below. The cholesterol is mixed in on the outside layer and in the inside.
You’ll also notice that there are cholesteryl esters inside (the inactive form).
These lipoproteins act similar to a submarine, floating through your bloodstream to take their cholesterol passengers from one place to another.
HDL, LDL, and VLDL (very low-density lipoprotein) all have similar shapes, although there are some important differences.
The most obvious difference is their size. Higher density objects carry more weight per a specific volume, which is why HDL particles are the smallest.
Take a look at the chart below to see how each type of particle differs by size. Note that each type of particle falls within a range of sizes, and can also carry different amounts of cholesterol.
Now there’s one more important difference I’d like to point out. On the image of the LDL particle, did you see the apolipoprotein B (apoB)? It’s a specific type of protein.
There is a single apoB molecule that only exists on LDL and VLDL particles. HDL contains apoAI instead. This is very important, so remember this distinction.
If Cholesterol is Good, Why is High Cholesterol Bad?
Here’s where it gets a little more complicated.
When a test (lipid profile) says you have a high total cholesterol, it’s referring to the cholesterol in your bloodstream (serum). This by itself is not a problem; it’s normal to have cholesterol circulating.
However, there is one situation that can have very dire consequences.
LDL, in particular, is able to cross through the inner layer of blood vessels into an artery wall. It doesn’t happen often, but the more LDL particles there are, the more likely it is to occur.
Once inside, the LDL can become oxidized. As you might know, oxidation and inflammation typically go hand-in-hand in the body. Oxidized LDL upregulates pro-inflammatory genes and activates the inflammatory signaling pathway (3).
This triggers white blood cells called macrophages to come and essentially try to eat the LDL (think of Pac-Man). However, in this particular case, the result is a foam cell, which is essentially just a macrophage filled with lipids.
The problem is that foam cells are the prototypical cells of atherosclerotic plaque (4). Over time, plaque buildup will cause arteries to get harder and narrower, known as atherosclerosis.
While it is possible for foam cells to re-enter the bloodstream and be cleared, the speed and effectiveness depends on a variety of factors (5). It’s pretty clear that the natural mechanism is not sufficient by the abundance of atherosclerosis cases, but it may be a key to an effective treatment one day.
Why HDL is the “Good” Cholesterol
Now just because all lipoproteins may look similar, it doesn’t mean they behave the same.
In fact, HDL can actually perform a process often called “reverse cholesterol transport”. It is able to extract any cholesterol in artery walls, and then take it back to the liver, where it is harmless (6).
While that’s the main benefit, it also has other antioxidant and anti-inflammatory functions, which keep your blood vessels healthy and clear (7). It deserves the name of the “good cholesterol”, and so far no amount of HDL is too high for good health.
What about VLDL?
So LDL in high amounts is bad, and HDL is good in high amounts. Now what about the other main lipoprotein, VLDL?
There’s currently no easy way to measure VLDL directly. It’s instead estimated based on triglyceride levels. All lipoproteins carry not only cholesterol, but also triglycerides. VLDL tends to carry much more of triglycerides than the other lipoproteins (which is why they are less dense).
So is VLDL a concern?
Yes, but probably less than LDL.
Smaller VLDL particles still have the potential to contribute to atherosclerosis, while the larger VLDL particles are unlikely to pass into the artery wall (8). In general, LDL is much more of a concern than VLDL, and is much easier to measure (9).
Does Size Really Matter? (A.K.A. Why Cholesterol Test Results Are Misleading)
The typical lipid profile test that you get from your doctor measures triglycerides, HDL-C, and total cholesterol. Sometimes LDL-C is measured, while other times it’s estimated.
What we’re interested in are the HDL-C and LDL-C. The “C” stands for cholesterol. Total cholesterol isn’t too useful, since the proportion of HDL and LDL changes its meaning significantly.
Recall that HDL and LDL can be thought of as submarines that are carrying cholesterol and triglycerides as their passengers.
HDL-C measures the total amount of cholesterol on all of the HDL subs. However, it doesn’t tell you how many subs there are, and that’s the big limitation.
As it turns out, when it comes to LDL, the amount of particles is more important to your risk of CVD than the amount of cholesterol in each LDL particle (10). Peter Attia explains this better than I could hope to.
Here’s the kicker: We can test for the number of LDL and HDL particles, it’s just a bit more expensive. Attia always tests for particle count with his patients.
Remember that all these measurements are just markers of CVD risk. Just because there is LDL or VLDL in your bloodstream, doesn’t mean it will end up in an artery wall. The science is still far from complete; we just know that when there are more LDL particles in your bloodstream, the likelihood increases that a particle will penetrate and become oxidized.
Everything You Need to Know About Paleo and Cholesterol
That’s more or less everything you need to know about cholesterol and any dangers it might present.
Unfortunately, like most things, there aren’t studies that look directly at the Paleo diet and cholesterol.
While there are a handful of things that can cause elevated LDL, we’re only concerned with a few.
Two common causes of a high LDL particle count are insulin resistance and metabolic syndrome (11)(12). It’s well-known that a Paleo diet can both decrease insulin resistance and reduce risk factors for metabolic syndrome.
When it comes to specific nutrients in a diet, things get much more complicated. The effect that a Paleo diet has on your LDL and HDL levels will not be the same as someone else. For example, more fat could raise your LDL levels, but it really depends on what you were eating before. The only really definite science out there is that trans fats raise LDL nearly universally, and may lower HDL (13).
A Final Caution about Cholesterol
You should monitor your LDL and HDL particle count before and after any major diet change.
However, you also need to remember that the science behind lipoproteins, cholesterol and CVD is far from complete. If you make a diet change and both your HDL and LDL go up a bit, that may or may not be a bad thing.
As long as your LDL isn’t extremely high and your HDL is extremely low, you probably shouldn’t worry about it. You should, of course, consult a doctor when interpreting any results, but make sure to find one who is up to date with the latest research.
If you made the switch to a Paleo diet and had your lipid profile completed multiple times, leave us a comment below and let us know how it went.