Thread by @DaveKeto

1/ Interesting thread via @ck_eternity_

I'll add some thoughts in my own thread to follow, but consider reading his entirely first.

As always, this is in the spirit of discourse. Love keeping it respectful and productive on such challenging topic. :)

https://twitter.com/ck_eternity_/status/1401952187006193665

2/ Before getting started, note the coming #LMHRstudy will effectively be tackling much of these common considerations quite directly as we study #LMHRs who have considerably high #LDL from being fat-adapted with otherwise #CVD healthy metrics (See CitizenScienceFoundation.org)

3/ While not commonly known, another major carrier protein for chol is Albumin. It's typically considered in light of transporting NEFAs, but its binding sites can (and are) applied to many other lipids, including cholesterol.
ncbi.nlm.nih.gov/pmc/articles/P…

https://twitter.com/ck_eternity_/status/1401952198553178113?s=20

4/ Technically, most ApoB100-containing lipoproteins leaving the liver are TG-rich VLDL that ultimately remodel to LDL, though some leave as TG poor LDL.

Small technical detail, but important for lipid profile disease associations and the LEM I work on.

https://twitter.com/ck_eternity_/status/1401952201518587910?s=20

5/ Of course, this is where the debate arises. I definitely think there is such a thing as dysregulated lipid metabolism, which I believe to be common with, say, atherogenic dyslipidemia (⬇️HDL+⬆️TG+⬆️%smLDL-P). However...

https://twitter.com/ck_eternity_/status/1401952204525867010?s=20

6/ ... I do regularly postulate per the #LipidEnergyModel a possible hypothesis to explain where higher LDL-C/-P/ApoB may even be expected given metabolic fat-adaptation.

Of course this is separate from the question of risk itself, which is where the coming study comes in.

7/ "...dietary cholesterol has little to no influence on blood cholesterol..."

My general expectation as well (but with some obv exceptions, such as genetic predis) Some interesting new data on this here => mdpi.com/2072-6643/13/6…

8/ "When LDL is elevated outside the normal range, it's associated with an increased rate of CVD"

The tweets that thread through this portion I leave for now as this is the reason we're working so hard toward the coming study. If true, #LMHRs are currently at very high risk

9/ I'll also pass on the SFA vs MUFA/PUFA trade off discussion. There are many variables end-to-end regarding lipoprotein (LP) synthesis, FFA ketogenesis vs TG esterification %, LP oxidative potential (and subsequent SR removal), and even the recent #HADLmodel to consider.

10/ Glad you added this at the end. Much of the debate in this space over LDL-C/-P doesn't often spend much time on the many areas of mutual agreement that have considerably more association with CVD than LDL.

https://twitter.com/ck_eternity_/status/1401953204741541890?s=20

11/ Moreover, I regularly bring to light how different the data looks when comparing combination lipid data (2 or more as profiles, such as AD or Met Syn) vs signal lipid data (looking at a lipid level in isolation). The former tend to provide a much stronger risk association.

12/ I think you'll definitely like our coming study. While I can't speak to any criteria yet or who will be enrolled, it will be interesting to see just how many have diets that are animal-centric, high in red meat, high in SFA, and/or low in MUFA/PUFA relatively.

13/ Again, great read -- @ck_eternity_. I'm always a fan of longer form threads (obviously I find myself doing a few as well 😂)