Understanding Cholesterol

Cholesterol and Diabetes

What is Cholesterol..?

Cholesterol is a waxy, fat-like substance that’s found in all cells of the body and is essential for life. It is actually a type of steroid. We eat it, we make it, we store it, and we excrete it – all in different amounts. Most of the cholesterol we eat is not absorbed and leaves our body in the stool.

Your body needs cholesterol to make hormones such as progesterone, testosterone, estradiol, and cortisol, is found in substances such as bile that help you digest foods, is used to create new and repair damaged cells, and its also converted to vitamin D when your body is exposed to sunlight.

Cholesterol is classified as a lipid. “Lipids” are defined as organic compounds that do not dissolve in water and include fats, oils, waxes, sterols (including cholesterol), and triglycerides.

Where does Cholesterol come from..?

Your body makes about 80% of the cholesterol needed and the rest comes from your diet. This is known as dietary cholesterol. About 20% of the Cholesterol produced or synthesised in the body is made in the liver and the rest by other body cells. If your diet is low in cholesterol then your body will either produce more, or re-absorb more from the bile in your gut to make up for the shortfall.

Cholesterol is transported in special vehicles

As lipids and fats don’t mix with water, they requires special transporters to move them around the body in the blood stream. These transporters are built from phospholipid molecules and proteins called apoproteins (also called apolipoproteins when bound to lipids) and are soluble in water. This phospholipid and protein wrapped “vehicle” that transports the lipids is called a lipoprotein and will typically consist of serveral thousand molecules.

In lay-mans terms a bunch of fatty molecules get wrapped by a bunch of other molecules (phospholipids and proteins) to make it soluble in water and this structure or vehicle is known as a lipoportien. You can think of a lipoportien as a ship. The phospholipids and protein form the hull and inside the cargo consists of lipids, mainly Cholesterol and Triglycerides.

You can think of a lipoportien as a ship. The phospholipids and protein form the hull and inside the cargo consists of lipids, mainly Cholesterol and Triglycerides.

Types of Cholesterol

Lipoproteins (ships) are formed by the liver (the shipyard) and are broken down into 5 different classifications based on density.

  • high density lipoprotein (HDL)
  • low density lipoprotein (LDL)
  • intermediate density lipoprotein (IDL)
  • very low density lipoprotein (VLDL)
  • chylomicron

You have probably heard that HDL is your good cholesterol and LDL is your bad Cholesterol. The reason given is that LDL delivers cholesterol to your bodys cells and in doing so has the potential to cause issues such as Atherosclerosis and Cardio Vascular Disease (CVD), while HDL collects excess Cholesterol and returns it to the liver.

This understanding has been proven to be inaccurate in recent years and we now know that most cholesterol returned to the liver is done so by LDL. However HDL lipoproteins do not have the potential to cause you diseases such as CVD as mentioned above and so their presence has no inherent risk.

LDL vs HDL

Each lipoprotein (ship) contains exactly one apoprotein. A protein can be likened to a chain or rope and wraps around the lipoprotein or ship. The apoprotein found on the shell of the lipoprotein (or hull of the ship), not only acts as a barrier to facilitate the transportation of the lipids but also contains the ability to communicate with other body cells. There are 2 special classes of apoproteins – “apoA-I” found on HDL lipoprotein particles and “apoB” residing on VLDL, IDL, LDL and Chylomicron particles.

The major function of the apoB-containing particles (or LDL ships) is to traffic energy (triglycerides) to muscles and phospholipids to all cells. Their cholesterol is then trafficked back to the liver. The apoA-I containing particles (HDL ships) traffic cholesterol to steroidogenic tissues (where steriods are created), adipocytes (a storage organ for cholesterol ) and ultimately back to the liver, gut, or steroidogenic tissue.

Chylomicron particles are the largest and least dense while HDL is the smallest and most dense. The lower the density the larger the particle. As LDL lipoproteins (LDL ships) leave the liver and circulate through the body, they undergo a process of maturation where they shed much of their triglyceride cargo in the form of free fatty acids. In doing so, this makes them smaller and richer in cholesterol. As the particles shrink some will be repackaged into a denser form by the liver, so a VLDL can become an LDL particle as it matures. This does not happen to all lipoproteins, only a percentage. Cholesterol transport occurs in both directions, towards the periphery and back to the liver.

Why is LDL bad..?

Only the lipoproteins containing “apoB” class apoproteins (LDL, VLDL, IDL, Chylomicron) have the ability to communicate with cells in the blood vessel lining. The lining of the blood vessels and arteries have a layer of special cells called “endothelial” cells and when these becomes damaged, inflamed or sore, apoB class lipoproteins will attempt to help repair the damage using the cholesterol contained within – like a “band aid” lying down on top of the damaged endothelium.

LDL becomes an issue as sometimes the lipoprotein passes through the damaged endothelial layer which initiates an immune response to destroy the rogue lipoprotein. This causes oxidation of the lipoprotein particle fixing it in place and causing it to take on an old and foamy texture.

As part of this immune response collateral damage occurs, which destroys other endothelial cells in the blood vessel lining. This causes a cascading effect, whereby more lipoprotein can get lodged in the blood vessel lining. Later bits of the foamy textured oxidized lipoproteins can break off causing more damage and necessary repair and the cycle continues until a plaque builds up. This causes hardening of the arteries and can lead to Atherosclerosis and Cardio Vascular Disease (CVD).

So if you want to lower the risk you need to lower the number of apoB lipoproteins (LDL,VLDL,IDL,Chylomicron) circulating in the blood.

Blood Tests and lipid Profile

A cholesterol test, also known as a Standard Lipid Panel, is what your doctor normally prescribes to assess cholesterol levels. This will measure you HDL-C (commonly known as your good cholesterol), LDL-C (commonly known as your bad cholesterol), your Total Cholesterol which is the sum of your LDL-C and HDL-C and also your Triglycerides level(fat that was digested).

HDL-C and LDL-C stand for “High Density Lipoprotein – Cholesterol” and “Low Density Lipoprotein – Cholesterol” respectively. This represents the amount of cholesterol (cargo) being transported in HDL and LDL particles (ships).

Blood is drawn into a tube and soon afterwards spun in centrifuge. This spinning separates out the different types of cells into layers. Importantly the lipoproteins are broken apart. ie your ships are blown totally apart. This allows the lab to calculate the total amount of Cholesterol and triglycerides (the ships cargo). They also count the number of apoA-I and apoB particles. Remember each HDL lipoprotein has one apoA-I and each LDL,VLDL,IDL,Chylomicron has exactly one apoB. So the lab can easily count the number of apoA-I proteins and determine the number of HDL lipoproteins in your sample. As HDL particles are all similar in size the lab can establish the amount of the Cholesterol found that was being carried in HDL particles and this is your HDL-C. However LDL is much more difficult to establish. How can they tell which of the apoB proteins belonged to the different types of LDL, i.e.  LDL, VLDL, IDL, Chylomicron. The standard lipid panel cannot tell and so a formula is used to estimate this.

Determining LDL-C

The following formula represents your total cholesterol.

Total Cholesterol = HDL-C + LDL-C +VLDL-C + IDL-C + Chylomicron-C

IDL-C and Chylomicron-C are eliminated from the equation as their number is deemed to be so low as to be negligible. This make the formula as such.

Total Cholesterol = HDL-C + LDL-C +VLDL-C

In the mid 1970’s a correlation between VLDL-C and Triglycerides (TG) was determined so that

VLDL-C = triglycerides count (TG) / 5

So the formula became

Total Cholesterol = HDL-C + LDL-C + TG/5

or put another way

LDL-C = Total Cholesterol – HDL-C – TG/5

This is how your LDL-C is calculated.

The reason why LDL-C is a poor indicator

As we saw above it is the number of apoB lipoproteins that matter, ie the number of LDL ships and not the size of the cargo. But here we are determining LDL based on total Cholesterol. ie the total cargo in our ships. What if all our ships are like large cargo ships, with each one carrying a very large cargo. In this case the number of ships could be small but the cargo would be large. The LDL-C calculation in this scenario would give a high result, but actually your risk is low. Conversely if my ships are like rowing boats, the cargo would be small and the number of ships large. The LDL-C calculation here would be low but really the risk is high.

So LDL-C is a poor indicator of lipid health. Rather than using the total cholesterol (cargo) as a basis for determining your risk of disease, you need to used the LDL particle count or LDL-P.

LDL-P (or apoB) is the best predictor of adverse cardiac events, which has been documented repeatedly in every major cardiovascular risk study.

 

LDL-C is only a good predictor of adverse cardiac events when it is concordant with LDL-P; otherwise it is a poor predictor of risk.

So why is LDL-C used at all..?

Firstly it is much cheaper than the alternative. And secondly many doctors believe that the LDL-C and LDL-P are concordant. That means if one is high the other will be high and if one is low the other will be low. This can be true, but often diabetics are shown to be discordant i.e. not concordant. So that means if your LDL-C is low and you think everything is good, your LDL-P could be high which puts you at high risk but nothing gets done. And the opposite is also true, if your LDL-C is high, your LDL-P may be low and you are at low risk, however your doctor believes you to be at high risk and a statin is most likely prescribed.

See this scattter plot from 2011 Otvos et al. paper. It shows the correlation of LDL-C and LDL-P for a given sample of people. Each dot represents one person. You can see that a large percentage of people lie outside the red lines which means they are discordant (not concordant) and thus the LDL-C result does not reflect their true health risk.

What Cholesterol tests should I get done?

The NMR (Nuclear Magnetic Resonance) Lipoprofile is a cholesterol test which provides more information than a standard Lipid Panel.  This test includes measurements for Total Cholesterol, LDL-C, HDL-C, Triglycerides, Insulin Markers, LDL-P and also LDL particle size and more.

This will give an accurate count – no estimations – of each type of LDL, HDL etc in your blood sample and will give you the real picture.