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What is Cholesterol?

Cholesterol is not something to be scared of

As you can probably tell, we love destroying myths of biology. And one of the tougher ones is the myth of cholesterol and what it does for you. Rather than be afraid of it, let’s try to understand it! You might be surprised at how important this little guy is.

You must have an understanding of what cholesterol is if you ever want to figure out why people claim it’s bad. Otherwise, you will end up like most people who just repeat stuff they heard on the news. It is imperative that you gain an understanding for yourself. Let’s begin.

What is cholesterol?

Most people do not understand this, so if you can get this, you are well ahead of the game. Cholesterol is one molecule – it has a single molecular structure. It does not come in different forms. This is what it looks like.[1] Just remember that it has one shape: it is one molecule. We cannot stress this idea enough.

 

Molecular structure of cholesterol

 

Its properties allow it to mix well with fat (long carbon chains) and somewhat with water (polar headgroup). It makes it ideal for interacting with the fat (phospholipids) that compose your cell membranes because they are similar in that way. Look at the picture below to see how cholesterol fits in to the membranes of your cell.[1]

 

Cholesterol in your membranes

The way people talk now-a-days, it seems like cholesterol comes in many forms. They make a distinction between things like HDL cholesterol and LDL cholesterol. Understand there is no difference between the cholesterol part of these phrases. Cholesterol is cholesterol. It does not come in different shapes or sizes. The things that carry them around (like LDL and HDL) are different, but the cholesterol is the same. We’ll get to those carriers in a second.

The main role of cholesterol is stabilizing the cell membranes. They help with membrane fluidity, permeability, and general organization.[1][2] It makes sure your cells don’t fall apart or leak substances. Other roles of cholesterol include the synthesis of steroids, hormones, and vitamin D.[2][3][4] We have all heard about how important all of these things are, so let’s start off with respecting the life-preserving roles cholesterol has.

Without cholesterol, there is no life. They play vital roles in biological function. People seem to forget that when talking about lowering your cholesterol levels… Don’t worry – we won’t let you forget.

Cholesterol transportation

One of the important properties of cholesterol is that it is fat soluble. That means it mixes really well with fat and lipids but not so much with water and blood. It is comfortable in the lipid membrane of your cells. Even though it has a polar headgroup, it is too small to allow cholesterol to be comfortable hanging out in water and blood. So, if it’s not comfortable floating around in blood, how is it supposed to get to the cells that need it? It can’t just freely travel in your bloodstream.

Your body has an excellent system in place for this to work. There are special transporters called “lipoproteins” that help with this.[5][6] They have the ability to hold fatty molecules (like cholesterol, triglycerides, and phospholipids) while moving freely in the blood. The properties of the lipoproteins allow cholesterol and triglycerides to travel in the bloodstream to get to where they need to go. You do not need to know much more than that, but there is a picture below for your reference.[7] The entire ball structure is the lipoprotein, and the arrows point to specific parts that make it up.

 

Structure of a lipoprotein

So, we have a molecule (cholesterol) that is very important for life, and now we have a way of actually allowing it to get to the cells. The lipoproteins are the boats, and the cholesterol and trigylcerides are the passengers. There is a little more to it than that, but really that is it in a nutshell. We are keeping it simple for now. Your cells need these fatty molecules to survive. The triglycerides (fats) are broken down and used to create energy (ATP) through fat metabolism. Cholesterol is used to stabilize membranes and help with hormone synthesis.

Types of lipoproteins (density classification)

The lipoprotein is known as the “particle” – if you have ever heard that word used in this context. It is the same thing as the lipoprotein carrier. Each type of lipoprotein particle is followed with a “-P” to distinguish it as the whole particle rather than the cholesterol.

When people talk about the different types of cholesterol, they are really talking about the different types of lipoproteins. The lipoproteins are what differ in structure. Even then, they do not really differ all that much. The main difference between the types is their density. The density changes depending on how much of their makeup is triglycerides.

Lipoprotein density chart

To recap, the lipoprotein mainly carries around triglycerides and cholesterol. What changes between the types of lipoproteins are the relative amounts of each of those. The higher amount of triglycerides, the lower the density. The lower the amount of triglycerides, the higher the density.[7][8] 

Particle classifications

Thus, we get the following classifications of lipoproteins:

  • HDL-P: high-density lipoproteins (low amount of triglycerides)
  • IDL-P: intermediate density-lipoproteins (medium amount of triglycerides)
  • LDL-P: low-density lipoproteins (medium amount of triglycerides)
  • VLDL-P: very-low-density liproproteins (high amount of triglycerides)
  • Chylomicrons: similar to VLDL (high amount of triglycerides)
    • They come from the intestine, so they have a different name.

As you go down the list, the amount of triglycerides that make up the lipoprotein gets larger and larger. Consequently, the amount of the lipoprotein that is cholesterol goes down. HDL, IDL, and LDL have relatively higher amounts of cholesterol (less triglycerides) than the VLDL and chylomicrons.

The VLDL and chylomicrons have more of the particle made up by triglycerides (fats). It is these fats that are used for energy by the cell. VLDL and chylomicrons are primarily the delivery system for fat to the cell. The other kinds deal more specifically with cholesterol delivery and return.[7][8]

Cholesterol classifications

The cholesterol that comes along with the lipoproteins is all the same, but they are labeled differently depending on which particle it is riding with. So additionally, you get more classifications of cholesterol even though they are the exact same molecule throughout:

  • HDL-C: cholesterol that rides with the HDL
  • IDL-C: cholesterol that rides with the IDL
  • LDL-C: cholesterol that rides with the LDL
  • VLDL-C: cholesterol that rides with the VLDL

For example, when people talk about LDL cholesterol, it is LDL-C they are talking about. LDL is really the lipoprotein that carries the cholesterol around. We hope you are starting to understand this point a bit better. The particle is the lipoprotein, and it’s composition varies depending on what it’s carrying. Cholesterol never changes, it just changes transporters.

Lipoprotein roles

Each of these kinds of lipoprotein particles has a very specific role. While we could go into excruciating detail, we are only going to summarize it. The general principles are still very applicable to understanding cholesterol’s purpose. Remember, cholesterol just rides along with the different lipoproteins. Below is a flowchart of the pathway lipoproteins take. Here only chylomicrons, VLDL, LDL, and IDL are shown because those are the particles involved in fat and cholesterol delivery. HDL has the very opposite function of returning cholesterol back to the liver.

 

Lipoprotein delivery of cholesterol and triglyceride flowchart

 


Chylomicrons and VLDL:

Both of these particles primarily transport fat (triglycerides) to the cells. That is their main role, and that is way they are mainly made up of triglycerides. Your cells need energy to live, and fat is one of those forms of energy. Cholesterol just happens to come along for the ride in case it is needed elsewhere down the particle’s pathway.

Chylomicrons and VLDL are pretty much the same thing. The difference is that chylomicrons come from your intestines (enterocytes). They involve the transport of fat from your food. VLDL is the lipoprotein that comes from your liver to delivery fat (from storage) to cells. They both do the same thing, but they start out in different places and have different sources of fat.

Once the chylomicrons drop off the fat to the cells (now “chylomicron remnants”), they go home to the liver. Their job is done. VLDL on the other hand drops off the fat and turns into IDL. Because it has less triglyceride content, it’s density rises just a little bit. Remember the cholesterol is still on board and hasn’t gone anywhere.


IDL and LDL:

IDL does not play a major role in all of this, but it is an intermediary step. Along with LDL, it has also been claimed to play a part in heart disease[9], so we want to address it. It either goes back home to the liver, or it undergoes more lipolysis to drop off the triglycerides. When it gives up more triglycerides is when we finally see LDL arrive. (The IDL raises its density just a bit by dropping off more fat.)

LDL has more cholesterol content than all the other lipoproteins before it. Here we see the role of lipoproteins change focus a little bit. The IDL/LDL will still be dropping off triglycerides, but LDL also has a role of taking cholesterol where it needs to go. LDL is the particle that will purposefully deliver cholesterol to cells.

Please understand this is a vital process for your body to go through. If LDL does not drop off cholesterol to the cells that need it, you would literally fall apart. It drops cholesterol off to be used in the stabilization of membranes and formation of hormones that we talked about before.[1][2][3][4] (We will talk about the implications of this a little later.)

Once it drops off its triglycerides and cholesterol, its job is finished and it goes home to the liver. That is a summary of the “delivery part” of the lipoprotein/cholesterol life. There is more complexity to this, but this pretty much sums it up. You now understand how your body gets fat for energy and cholesterol for repair.

Oh… Did we just say “repair?” Whoops, that must have slipped… We meant to bring that up later, but, yes, cholesterol gets delivered to places that need it. That includes cells and tissues that are inflamed / harmed and need repair. More on that later. Right now, let’s look at the final lipoprotein: HDL


HDL

HDL is different from all the others because it leaves the liver to go pick up cholesterol rather than to drop it off. The cells use the cholesterol for many things, but that does not mean it always uses it up completely. Your body has a perfect pathway to take care of that: reverse cholesterol transport through HDL. This lipoprotein will come and pick up the cholesterol when the cell is done with it. It brings it back home.

 

HDL pathway - cholesterol pick-up

HDL is always referred to as the “good cholesterol.” It clears the cholesterol from arteries and even has anti-inflammatory effects.[10] But remember HDL is only a transporter. Cholesterol is still cholesterol. It is now just in a different boat than before. When riding with HDL, it is on its way home from a long voyage. HDL is good in our eyes, but so are all the others! This entire system is one beautiful mechanism for delivering fat, cholesterol and phospholipids to your cells.

Each particle plays a vital role, so we should not automaticall demonize the LDL as being “bad.” We have to look at why our body has it in the first place.

Why does cholesterol build up in arteries?

If you caught our slip-up before, you saw that we said cholesterol goes to places that need repair. Well, one of those places that need repair is the wall of your arteries. If you have damaged artery walls (or any damaged tissue), through things like inflammation or oxidative stress, cholesterol will come to easy the pain.[11][12][13] We will actually dedicate an entire blog post to this subject because it is so important to understand.

But remember that cholesterol is vital to life. It servers many purposes. If you have a place that constantly needs repair (like lesions on artery walls), then the cholesterol will come to take care of the problem. It might not always work because there is just so much inflammation going on. Thus, the cholesterol starts to build, maybe even gets oxidized, and it can start doing other damage – like blocking the flow of blood.

 

Cholesterol and plaque build-up in arteries

But the cholesterol was not the problem! The problem was the inflammation. A build up of cholesterol and plaque is a bad sign because it means something deeper is wrong. That being said, having high cholesterol in your blood is not necessarily bad. In fact, it can be a really good thing if fat is your main source of energy. The fat gets delivered with VLDL and LDL, and the cholesterol comes along for the ride. There is just going to be more of it because you get more energy from fat.

Keto raises cholesterol

That’s why the ketogenic diet will raise your cholesterol levels. It’s really raising the amount of fat delivery you need – which makes perfect sense! It is a necessary and beautiful thing for this to occur. The problematic stuff is the plaque build-up, not the cholesterol in your blood. On the following pages and follow-ups, we will go through exactly how to read your high cholesterol levels. There are bad signs to watch out for, but the problem is not the cholesterol.

Having firemen around means there was a problem. Gather too many of them, and they start interfering with people’s processes. Other problems arise because of their over presence – but they only stay there if they need to fight a fire! The firemen are not the problem – they just signal that there was a problem before..

High cholesterol

If you do have high LDL cholesterol, you must ask yourself, “why?” Is it because you are mainly a fat-fueled machine now? If so, then it is totally normal. Also, cross-check it with your triglyceride levels. If your triglyceride levels are low, then it means your cells are actually using the fat as energy – there is nothing to be worried about.

You should also check your inflammatory markers. If they are low, then, again, you have nothing to worry about. Your heart will be fine.

Do not be afraid of high cholesterol

But if you are using fat for fuel mostly (like a keto-goer) and you have high triglycerides, then you have problems coming your way. You must be an engineer and ask why there are so many triglycerides in your blood. It can mean that your cells are not properly taking in the fat to use for energy.

This means your mitochondria are not working properly, and you could get something like insulin resistance. There are a number of possible problems that lead to fat not getting into your cells.

The issue of fat in-take and high triglycerides is another issue on its own. But once we understand our biology, we can start asking the right questions and get to the bottom of the problem of heart disease. We can then tackle all of the other issues from a root-cause point of view.

We can start to ask things like: “What is the real problem here?”

References:

[1] Maxfield FR, Tabas I. (2005). Role of cholesterol and lipid organization in disease. Nature 438: 612-621.

[2] Campbell, NA, et al. (2017). Campbell Biology in Focus. Pearson Education Limited.

[3] “Cholesterol | chemical compound”. Encyclopedia Britannica. (2018). [Online]. Available: https://www.britannica.com/science/cholesterol. Accessed: 13 May 2018.

[4] Miller WL. (2013). Steroid hormone synthesis in mitochondria. Molecular and Cellular Endocrinology 379(1-2): 62-73.

[5] Ordovas JM. (2003). Lipoproteins. Encyclopedia of Food Sciences and Nutrition. 2nd ed. p.3543-3552.

[6] “Lipoprotein | chemical compound”. Encyclopedia Britannica. (2018). [Online]. Available: https://www.britannica.com/science/lipoprotein. Accessed: 13 May 2018.

[7] Feingold KR, Grunfeld C. Introduction to Lipids and Lipoproteins. [Updated 2018 Feb 2]. In: De Groot LJ, Chrousos G, Dungan K, et al., editors. Endotext [Online]. South Dartmouth (MA): MDText.com, Inc.; 2000. Available: https://europepmc.org/books/NBK305896;jsessionid=155DAE5F42718E4579070AD02C0D7F2B

[8] Lewis B. (1973). Classification of lipoproteins and lipoprotein disorders. Journal of Clinical Pathology Supplement (Ass. Clin. Path.) 5:26-31.

[9] Tatami R, Mabuchi H, Ueda K, et al. (1981). Intermediate-density Lipoprotein and Cholesterol-rich Very Low Density Lipoprotein in Angiographically Determined Coronary Artery Disease. Circulation 64(6): 1174-1184.

[10] Link JJ, Rohatgi A, de Lemos JA. (2007). HDL Cholesterol: Physiology, Pathophysiology, and Management. Current Problems in Cardiology 32(5): 268-314.

[11] Wong AP, Mohamed AL, Niedzwiecki A. (2016). Atherosclerosis and the Cholesterol Theory: A Reappraisal. World Journal of Cardiovascular Diseases 6(11): 391-409.

[12] Berghoff SA, Gerndt N, Winchenbach J, et al. (2017). Dietary cholesterol promotes repair of demyelinated lesions in the adult brain. Nature Communications 8: 14214.

[13] Malhotra A, Redberg R, Meier P. (2017). Saturated fat does not clog the arteries: coronary heart disease is a chronic inflammatory condition, the risk of which can be effectively reduced from healthy lifestyle interventionsBritish Journal of Sports Medicine 51(15): 1111-1112.

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