It is very simply calculated: you just subtract HDL Cholesterol (HDLc) and LDL Cholesterol (LDLc) from your Total Cholesterol. For example, if your Total Cholesterol were 300, your LDLc 200, and HDLc 80, then you’d have a Remnant Cholesterol (RC) of 20. That’s 300 – 200 – 80 = 20.
You can be forgiven if you thought Total Cholesterol was simply LDLc + HDLc. I thought so too before I was into keto since I was always told, “cholesterol is divided into two types, LDL and HDL…” — wrong! That little gap of cholesterol left over is very, very meaningful. When fasted, it is the cholesterol found in Very Low Density Lipoproteins (VLDL) and Intermediate Density Lipoproteins (IDL). When not fasted, it includes those two and Chylomicron Remnants.
Why This is a Problem
The lipoproteins mentioned above aren’t supposed to be hanging around in the blood for very long. VLDLs pop out of the liver ready to drop off fat-based energy in the form of Triglycerides (TG) from the getgo. They bounce around your vascular system binding to tissues that need the energy and get smaller and smaller from less cargo in the process. From there they are remodeled to IDLs, which are then cleared by the liver or remodeled again to an LDL. This succession of stages to the final LDL takes under 90 minutes. So how long do LDLs hang out? 2-4 days!
This is worth reemphasizing because it’s key to understanding Cholesterol Remnants. Again:
- VLDL half-life is 30-60 minutes
- IDL half-life is less than 30 minutes
- LDL half-life is 2-4 days
So given this, we’d fully expect that the vast majority of lipoproteins that originated from the liver would be in that final LDL stage, even if they started out as VLDLs, right? Yes, of course!
A Simple Traffic Analogy
So imagine it this way… you have two jobs. When you leave the house in your car, you have a lot of food which you then drop off to people around the neighborhood who are hungry. This is supposed to take 1-2% of your time.
The other 98-99% of your time is spent doing the other job — patrolling the same area to help out in other ways. You might be doing citizen arrests of robbers (binding to pathogens) or helping out repairing houses that need it (non-hepatic endocytosis).
But what if there’s a problem with the roadways such as a traffic jam or you’re having a tough time finding people to take any of the food you’re offering (exceeded personal fat threshold). So now you’re spending much more time in that first job because there’s a widespread problem throughout the neighborhood that’s holding you up (and your fellow delivery drivers as well).
How They See It vs How I see It
I’ve been obsessively reading these Remnant Cholesterol papers for a while now. And this is a common opinion among them:
Remnant cholesterol, also known as remnant lipoprotein, is a very atherogenic lipoprotein composed primarily of very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL).
So VLDLs and IDLs themselves are “very atherogenic”?
Let me offer an entirely different viewpoint.
As many long-time readers know, I certainly see the lipids and their containing lipoproteins in our bloodstream as primarily an energy distribution system. That first tiny little stage of delivering energy as VLDLs or Chylomicrons is arguably the bulk of their “work.” Sure, it is done so quickly that it might seem like it is a small part of it. But when you see their largest payload is fatty acids (in the form of triglycerides) and their most reliable “activity” is hydrolyzing it off to the tissues that need it, you realize these guys just aren’t procrastinators, they get the biggest job done early and quickly…
… except when they don’t.
I offer two major reasons VLDLs and IDLs would be slowed down from remodeling to LDLs:
- VLDLs aren’t effectively distributing fat-based energy (triglycerides) and thus they have longer residence time before they can move on (remodel) to their next stages.
- The lipid system is being employed to a higher degree in fighting or repairing a disease state. I won’t be covering this point here, but I’ll return to it in another post.
The first point is well illustrated in many who have hypertriglyceridemia, a commonly associated CVD risk. Often they have a much higher proportion of VLDLs. Why? Not surprisingly, these are likewise associated with hyperinsulinemia and metabolic syndrome.
Perhaps Broken Systems are Atherogenic, Not Lipoproteins?
To put it simply, a problem arrises when the fat-based energy has few places for the VLDL to park it. Those places it does park often can’t stay there long if one is well past their personal fat threshold. The fatty acids keep spilling back out into the bloodstream, binding to albumin, and finally making their way back to the liver to… wait for it… get repackaged into a VLDL again. You see the cycle?
A hypothesis: VLDLs, IDLs, and LDLs are not independently atherogenic, but a body that is undergoing oxidative stress, chronic inflammation, or hyperinsulinemia can be. Yes, lipoproteins participate in this process as that is one of the many “hats” they wear in trying to fight it off and/or repair it. But trying to identify a single lipoprotein to label as the bad guy misses the point of the larger perspective on what’s happening inside the body to begin with.
Remnant vs LDL Cholesterol
Here’s a couple of example RC studies:
From this study: “CONCLUSIONS: Both lipoproteins [RC and LDL] were associated equally with risk of IHD and MI; however, only nonfasting remnant cholesterol concentrations were associated stepwise with increased all-cause mortality risk.” (See graphic at right from the study)
From this study: “CONCLUSIONS: Increased concentrations of both calculated and measured remnant cholesterol were associated with increased all-cause mortality in patients with ischemic heart disease, which was not the case for increased concentrations of measured LDL cholesterol. This suggests that increased concentrations of remnant cholesterol explain part of the residual risk of all-cause mortality in patients with ischemic heart disease.”
I’m hesitant to name any single lipid marker as the “best” one to measure. But if I had to choose right now, I’d be pointing to Remnant Cholesterol (RC). As of this writing, I haven’t found a single study that includes RCs in matchups with other lipids where it isn’t the clear winner in predicting all-cause mortality.
At a minimum, one should be looking at Remnant Cholesterol over LDL Cholesterol. That’s why I added a new tool for people to check their Remnant Cholesterol here on the site. Feel free to do yours and share the results in the comments section.
What This Means for Low Carbers
While I have read through a lot of these studies, I still consider this early in my research on it. I’m naturally thinking through the mechanics and how it applies to those who are LCHF and thus powered by fat.
Here’s a summary of my notes thus far:
- Given the data I have so far from the followers of this site, those going LCHF/Keto will more likely to see an improvement in their RCs, even if they are a hyper-responder.
- Ironically, the reference range for RCs as they apply to those on a fat-based diet may actually be inflated. In other words, I’d expect RCs to actually be higher for appropriate mechanistic reasons given the higher proportion of distribution by VLDLs when LCHF/Keto.
- Like triglycerides, RCs seem to be a great “cheat detector” within my own group of family and friends. Anecdotally, when they fall off the wagon and have too many carbs while still being very high fat, their RCs tend to go up.
Final Note on Fasting vs Non-Fasting Remnants
Lastly, I should warn that much of the newer research on Remnant Cholesterol compares populations who have had non-fasted lipid numbers. I suspect this will not work for those on LCHF/Keto. I’ve already found in my own data and those of others that when on a fat-centric diet, you can often have higher triglycerides relative to a carb-centric diet when taking lipids while not fasted. Hello! You are literally observing triglycerides from the food you just consumed as part of the total amount found in the blood.