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Remnant Cholesterol

Have you heard of remnant cholesterol before?

No? Great! It is actually a very easy concept. But before we get started on the remnant cholesterol

Let’s make sure you are able to calculate it! This is a classification of cholesterol that you want a number for. Next time you go get a blood test and lipid panel, make sure you calculate your remnant cholesterol. It is actually really easy, so don’t be intimidated!

They do not measure this amount directly – you have to pull out some old math skills. Take total cholesterol and subtract off HDL & LDL from that number (RC = TC – LDL – HDL). Check out the example below:

  • Total cholesterol = 250 mg/dL
  • LDL cholesterol = 150 mg/dL
  • HDL cholesterol = 80 mg/dL
  • Remnant cholesterol = 250 – 150 – 80 = 20 mg/dL

So the remnant cholesterol for this person is 20 mg/dL, and he is in the “low risk” quintile. Wasn’t that easy? Now you can go do that and ask your doctor about it when you go get blood work done next.. We wouldn’t be surprised if your doctor hasn’t even heard of remnant cholesterol before. Most doctors don’t learn about stuff like this. They just learn symptoms and drug remedies – a big game of match the diagnosis with the pill.

 

Risk profile for remnant cholesterol levels


Based on this study, you ideally want your remnant cholesterol to be at 15.5 mg/dL or below. Really though, anything between 15.5 – 27 mg/dL shows a very slight increase in risk. We would say that anything under 27 mg/dL is going to be okay. Again, these are just numbers associated with heart disease. Above is a summary of the risk profiles. This should help you see what sort of risk category you fall into. These informal levels are not standard with any organization, they are just from a published study. Use them for reference, but understand these understandings are still in their infancy.

Quick review on cholesterol

Have you got a decent grasp of the general overview of cholesterol? What is it? What are its roles?

If not, then go back to this page to learn more about all the important roles cholesterol plays and why, perhaps, it rises when we eat a high fat diet. You must understand its function in order to understand we should not be afraid of it.

To summarize, lipoproteins play a necessary role in energy and cholesterol delivery. Cholesterol plays a role in many processes like helping the cell membrane maintain integrity, hormone synthesis, and vitamin D formation. It is very important to life – without it, life does not exist

Molecular structure of cholesterol

Cholesterol rides the lipoprotein boat around the blood. The classifications of cholesterol come form what boat it is on (LDL, HDL, ect.) When there are certain problems in the arterial walls, that’s when cholesterol “gets stuck.” But this is a consequence of a bigger problem – not the problem itself.

Now that you understand “cholesterol” is just a molecule used for certain functions, and that it just happens to get caught up in nasty processes, then we can start looking at why certain types of cholesterol particles are good markers / predictors of heart disease.

(Pay close attention there. They can be markers, but they are not, in and of themselves, the problem.)


Remnant cholesterol is exactly what it sounds like. It is all the cholesterol “left over” and hanging out in your blood stream. Remember that cholesterol particles change form when they drop off the triglycerides? When they are not able to do this properly, they stay in their current state for a longer period of time. That is usually a bad sign.

Technical definition of remnant cholesterol

Remnant cholesterol is everything that is not LDL or HDL cholesterol. There are 5 main types of cholesterol: chylomicrons, VLDL, IDL, LDL, and HDL. When you go get a lipid panel, they measure your total cholesterol. That is everything and anything included in the list above. Typically you will be fasting (~12 hours) for a lipid panel, so that means your chylomicrons will not be a part of that. They have a very short half life of only about 10-20 minutes.[1][2]. (You can get a non-fasting lipid panel in which your chylomicrons will be a part of it.)

 

Remnant cholesterol is everything that is not LDL and HDL


Yep – it is pretty much everything that is involved in the “energy delivery” part of the job. If they are supposed to be delivering energy (fat) and then moving on to the other “stages” of cholesterol, but can’t, that means there is a problem. VLDL & IDL are only supposed to hang around for a few hours and then transform into LDL.

  • VLDL has a half life ranging from 30 minutes to 4 hours.[2][4]
  • IDL has a half life of 1-2 hours.[5]

In a healthy person, there shouldn’t be much of the remnants hanging around. It means they weren’t able to drop off their energy. Once they drop off the fat, they eventually get to LDL, which has a much longer lifespan. LDL has a half life of about 3 days![6] That is much longer than the other kinds of cholesterol – so it should make up a very large portion of your total cholesterol.

Why don’t test usually include chylomicrons?

The reason fasting lipid tests don’t include the chylomicron count is not just because it has a short half-life. It is also because they only appear when you eat fat and cholesterol.[7] They are there for dietary lipid transport, so if you don’t eat fat, then you don’t measure those lipoproteins.

On the other hand, VLDL shows up because the liver produces it endogenously when cells need energy or things need repair.[7][8][9] More delivery comes from VLDL in the fasted state than comes from chylomicrons. Thus, you should have some VLDL floating around during your test. But it should not be too high, or that means it wasn’t able to do its job, so it is just lingering. It has a pretty short half-life, and it should move on quickly.

The problems of remnant cholesterol

Remnant cholesterol has reached a state of recent popularity. Researchers have shown a correlation with ischemic heart disease, even more strongly correlated than many of the other risk factors we’ve looked at.[10][11][12] And indeed, there is strong data showing the relationship. The mechanism is still not totally understood, but there is certainly a correlation.

 

Remant cholesterol correlated with heart disease


And they are not even just correlations. Some researchers claim a causal relationship between the remnant cholesterol and heart disease.[10][11] But the tricky thing about these claims are that they are not based on randomized clinical trials. But we will get into the problems of the research in a bit. Let’s just look at why there may be a relationship between high cholesterol of this type and heart problems.

Possible issues

No research has been able to definitively explain why cholesterol (and remnant cholesterol) causes heart problems. Maybe the high cholesterol is more of a symptom than the problem. That is what we suggest to be the case. As for now, the clinical trials show that high cholesterol does not mean there is higher mortality from heart events.[9] That means we should focus less on cholesterol as causing it, and more on cholesterol happening to be there when it happens. Below are our versions of why high remnant cholesterol is related to heart disease.


If there is a whole bunch of cholesterol hanging around in your blood, then it hasn’t done its job. Usually when a biological substrate has not done its job properly, there is a problem. There is also the possibility that the energy is getting dropped off just fine, but the cholesterol is stuck in traffic. There might be some damage to arterial walls that the cholesterol has come to help. It just gets stuck along the way.

If there is a weak extracellular matrix on the arterial walls, then cholesterol can get stuck, oxidized, and eaten by macrophages to form foam cells.[13] We suspect that would be most of the reason why plaque contains cholesterol at all. Cholesterol is not the root cause of the problem. But perhaps having more remnant cholesterol (that should have otherwise “moved on”) increases the chance of particles getting stuck in the walls.

 

Weakened arterial walls might be the root causes - maybe from inflammation..


Or maybe the fact that there was no energy drop off signifies that your cells have lost the proper receptors. If that is the case, there is a good chance that arose out of chronic inflammation. That inflammation would also cause problems in the arterial wall. Thus, inflammation is a double whammy here. The lipoproteins can’t drop off fat, and then they get held up in traffic because the cholesterol wants to go mediate the inflammatory problems and lesions of the artery.


There are so many possible mechanisms, but there are no enlightening studies on why remnant cholesterol hangs around. But there is certainly reason to believe that it is there because of some other problem. Understanding cholesterol roles does not lead us to think it could ever be causal in atherosclerosis. Now let’s look at some of the problems of those referenced research papers.

Problems with the research

The first problem is that all of the research on remnant cholesterol has been from observational and epidemiological studies. These were not randomized controlled trials, which is the standard for medicine. We do not want to say that causes the research to be meaningless. In fact, that is a very important part of understanding disease.

Also, the people who tend to have high cholesterol are not doing it because they are purposefully following a strict high fat ketogenic diet (like we are). They most likely are also eating a whole bunch of junk food that happen to use fats. The other parts of the junk food cause problems around the cholesterol, and then the cholesterol comes to help and sticks.

People who follow a high fat diet on purpose (and thus raise their cholesterol) have improved markers of heart disease, like triglycerides.[14][15] That shows it is not a rise in cholesterol alone that is a problem. It is probably from the other parts of the diet that cause inflammation and such.

There isn’t a whole ton of research on people actually following a ketogenic diet, so it is hard to pull conclusions. But the research that does exist suggests that rising cholesterol levels from a ketogenic diet are not harmful. Most studies on cholesterol do not look at people who are low-carb. So if somebody has a whole bunch of cholesterol with their inflammatory carbohydrates, then that makes sense it is problematic!

We have to do more research on low-carb cholesterol, specifically. That is how we can start to determine the true root cause of heart disease.

References:

[1] Cesar TB, Rita M, Oliveira M, Mesquita CH, Maranhao RC. (2006). High Cholesterol Intake Modifies Chylomicron Metabolism in Normolipidemic Young Men. The Journal of Nutrition 136(4): 971-976.

[2] Goldberg IJ. (1996). Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenesis. Journal of Lipid Research 37: 693-707.

[3] Dayspring T. “Triglyceride Transport”. Lipid Center. [Online]. Available: http://www.lipidcenter.com/pdf/TG_and_VLDL_Physiology.pdf. Accessed: 31 May 2018.

[4] Krisko TI, Armstrong EJ, Cohen DE. “Biochemistry and Physiology of Cholesterol and Lipoprotein Metabolism”. Basicmedical Key. [Online]. Available: https://basicmedicalkey.com/pharmacology-of-cholesterol-and-lipoprotein-metabolism/. Accessed: 31 May 2018.

[5] Dayspring T. “Lipid and Lipoprotein Basics”. Lipid Center. [Online]. Available: http://www.lipidcenter.com/pdf/Lipid_and_Lipoprotein_Biochemistry.pdf. Accessed: 31 May 2018.

[6] Langer T, Strober W, Levy RI. (1972). The metabolism of low density lipoprotein in familial type II hyperlipoproteinemia. The Journal of Clinical Investigation 51(6): 1528-1536.

[7] Feingold KR, Grunfeld C. (2000). “Introduction to Lipids and Lipoproteins”. South Dartmouth (MA): MDText.com, Inc. [Online]. Available: https://europepmc.org/books/NBK305896;jsessionid=155DAE5F42718E4579070AD02C0D7F2B. Accessed: 31 May 2018.

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

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

[10] Varbo A, Benn M, Nordestgaard BG. (2014). Remnant cholesterol as a cause of ischemic heart disease: Evidence, definition, measurement, atherogenicity, high risk patients, and present and future treatment. Pharmacology & Therapeutics 141(3): 358-367.

[11] Varbo A, Benn M, Tybjaerg-Hansen A, et. al. (2013). Remnant Cholesterol as a Causal Risk Factor for Ischemic Heart Disease. Journal of the American College of Cardiology 61(4): 427-436.

[12] McPherson R. (2013). Remnant Cholesterol: “Non-(HDL-C + LDL-C)” as a Coronary Artery Disease Risk Factor. Journal of the American College of Cardiology 61(4): 437-439.

[13] El Asmar MS, Naoum JJ, Arbid EJ. (2014). Vitamin K Dependent Proteins and the Role of Vitamin K2 in the Modulation of Vascular Calcification: A Review. Oman Medical Journal 29(3): 172-177.

[14] Yancy WS, Foy M, Chalecki AM, Vernon MC, Westman EC. (2005). A low-carbohydrate, ketogenic diet to treat type 2 diabetes. Nutrition & Metabolism 2: 34.

[15] Phinney SD, Horton ES, Sims EA, Hanson JS, Danforth E Jr, LaGrange BM. (1980). Capacity for moderate exercise in obese subjects after adaptation to a hypocaloric, ketogenic diet. The Journal of Clinical Investigation 66(5): 1152-61.

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