1/ Thread:
***Why LDL and ApoB Shouldn't be used Interchangeably!***
I think there's a very serious problem resulting from confusion on these two markers that may appear to be exactly the same, but aren't.
Knowing the difference can explain quite a lot...
***Why LDL and ApoB Shouldn't be used Interchangeably!***
I think there's a very serious problem resulting from confusion on these two markers that may appear to be exactly the same, but aren't.
Knowing the difference can explain quite a lot...
2/ First, you need to know the typical lineage of an LDL particle. How did it start out?
An LDL usually starts out as bloated with triglycerides (TGs) with a few other proteins on it and is known as a VLDL (very low density lipoprotein).
After dropping off TGs, it remodels...
An LDL usually starts out as bloated with triglycerides (TGs) with a few other proteins on it and is known as a VLDL (very low density lipoprotein).
After dropping off TGs, it remodels...
3/ ... to an IDL (intermediate density lipoprotein) and then many go on to become LDL (low density lipoprotein).
Now there's one thing VLDLs, IDLs, and LDLs have in common -- they all carry with them exactly one copy of a protein called ApoB throughout their lifecycle.
Now there's one thing VLDLs, IDLs, and LDLs have in common -- they all carry with them exactly one copy of a protein called ApoB throughout their lifecycle.
4/ So in a sense, VLDL, IDL, and LDL are all "stages" in an ApoB lipoprotein* that comes from the liver.
*(Technically, some hepatic ApoB lipoproteins can start out as LDL, but we'll save that for another time)
*(Technically, some hepatic ApoB lipoproteins can start out as LDL, but we'll save that for another time)
5/ And get this, VLDL and IDL stages are extremely short compared to the LDL stage:
VLDL - 30-60 minutes
IDL - 30 minutes
LDL - 2-4 days!
Which means in a healthy metabolism, it is common to see 95%+ LDLs and far less VLDLs and IDLs.
Thus, 95%+ of ApoB are LDLs, right?
VLDL - 30-60 minutes
IDL - 30 minutes
LDL - 2-4 days!
Which means in a healthy metabolism, it is common to see 95%+ LDLs and far less VLDLs and IDLs.
Thus, 95%+ of ApoB are LDLs, right?
6/ Hold it! Here's where it's easy to miss the fine print.
Note I qualified "in a healthy metabolism"
What happens in an *un*healthy metabolism -- particularly one where someone is, say, hyperinsulinemic T2D?
Do we see only a tiny fraction of their ApoB as VLDL? Often we don't
Note I qualified "in a healthy metabolism"
What happens in an *un*healthy metabolism -- particularly one where someone is, say, hyperinsulinemic T2D?
Do we see only a tiny fraction of their ApoB as VLDL? Often we don't
7/ Let's return to our lineage again, only this time I want to overlay that important part on dropping of the TGs, because that's all a part of energy delivery to tissues.
See the dotted line? VLDL and IDL residence time is heavily influenced by the successful delivery of TGs.
See the dotted line? VLDL and IDL residence time is heavily influenced by the successful delivery of TGs.
8/ I have and continue to make the case that the high VLDL/IDL (and other remnants) we see in hyperinsulinemia (T2D, etc) is commonly a clear indication of metabolic dysregulation.
Simply stated, I posit this is high level energy delivery failure, and that's generally very bad.
Simply stated, I posit this is high level energy delivery failure, and that's generally very bad.
9/ So can we just look at VLDL/IDL (as well as other remnants) *without* including LDL?
Yes -- it's already identified in the literature as "remnants".
And in fact, one can look at "remnant cholesterol" as it is far more associated with ASCVD than LDL-C.
Yes -- it's already identified in the literature as "remnants".
And in fact, one can look at "remnant cholesterol" as it is far more associated with ASCVD than LDL-C.
10/ Which brings us back to the problem of looking at ApoB.
ApoB lumps in both remnants and LDL.
Given remnants have a massive association by itself without LDL -- using ApoB manages to attach LDL to the outcomes anyway so it's sure to get the blame.
ApoB lumps in both remnants and LDL.
Given remnants have a massive association by itself without LDL -- using ApoB manages to attach LDL to the outcomes anyway so it's sure to get the blame.
11/ I'll have new data to share soon regarding ApoB when looked at with low triglycerides (and thus, low triglyceride-rich remnants).
And of course, this is very relevant to low carbers given they often have very high ApoB, yet very low triglycerides.
And of course, this is very relevant to low carbers given they often have very high ApoB, yet very low triglycerides.
12/ So the tl;dr--
Remnants have a high association with ASCVD and all cause mortality.
ApoB lumps remnants and LDL together, thus creating the impression LDL has this high risk association where likely far more remnant-related.
Solution: don't use ApoB and LDL interchangeably
Remnants have a high association with ASCVD and all cause mortality.
ApoB lumps remnants and LDL together, thus creating the impression LDL has this high risk association where likely far more remnant-related.
Solution: don't use ApoB and LDL interchangeably
