Thread by @DaveKeto

1/ About to do a live listen+tweet on @IanCramer's recent podcast w/ @POhukainen as they talk #lipids!

Before starting, I want to note @IanCramer is the first #PlantBased podcaster to invite me on his show and I'm honored accept. Hopefully recording soon. plant-basedcyclist.com/icp-80-dr-paul…

2/ 9:25 — Pauli opens up on lowering his use of “the D word” to improve the “communication strategy”. 👏 👏

naturally, I’m a huge fan of keeping the personal separate from professional. Adding a little noise to the signal just keeps many focused on the noise.

3/ there are actually a handful of times where Pauli would go on a big Twitter thread that I really wanted to retweet — but it included too many personal jabs. I think that’s really changed in recent times (hence my recent retweet of one of his threads)

4/ I’d love to also add that I’ve had many great conversations with Pauli. I know we all get caught up in the social media debates & things can get heated. But there are many people who I disagree with on key fundamentals but still respect for their many great insights, he is one

5/ 43:32 “ in general... it’s thought to be... the purpose of an LDL particle is to transport cholesterol to peripheral cells that might need it”...

6/ (he discusses how cells can make their own cholesterol, then a few minutes later...) “ we don’t know of [any situation] where cells would be in serious need of cholesterol”...

this is a super relevant area to me, of course

7/ “so the stuff that’s going around in the blood seems to be a kind of backup system” — agree!

8/ 54:40 "Endothelial cells have this property where they take up... lipoprotein particles from one side of the cell... and out the other side of the cell. This is the way they move from the blood, through the endothelium into the arterial wall..."

9/ "Because in the arterial wall there are also some of these cells that might need a little bit of extra cholesterol now and then. So there needs to be this system so some of them can also use it." 🤯 Pauli and I agree much more than I thought!...

10/ I think it's worth taking a moment to unpack this a little bit. The process he's referring to is transcytosis. It's actually an extremely controlled transporting mechanism in these cells and requires a lot of signaling end-to-end...

11/ In my opinion, you can't really crack open the book on atherosclerosis until you can confirm how much of its constituent parts (cholesterol, apolipoproteins, macrophages, fibrin) are there by defect or design. Which is why transcytosis is such an important component to study

12/ It may indeed be that its only value is in providing lipoproteins through migration to adjacent cells. But even if this is so, it suggests demand on the part of those cells for this process as well, which may also be an important part of the puzzle.

13/ Oh boy -- at 55:45 we get into the proteoglycans. Pretty straightforward section. I think Pauli does a pretty good job of describing the modern pathological view in this context regarding atherogenesis.

14/ Part I complete. I think I'm just going to flip to part 2 and keep it in this same thread...

15/ 4:28 Ian kicks it off "The common view that I've heard from many physicians -- at least, whole foods plant based -- but I feel that this is the current paradigm... we want to keep [LDL cholesterol] as low as possible, for as long as possible. Do you agree with that?"...

16/ Pauli: "Yes, yes, yes -- that's something that from a population level pretty robustly shows that."

I hope @IanCramer will ask me the same question. I'm saving my answer for that podcast interview. :)

@IanCramer 17/ 6:57 Pauli: "What's the effect of genes on your blood lipids?... Some of the more commonly cited estimates range between 40 and 50%."

@IanCramer 18/ I have to say, I'm really enjoying @IanCramer's interview style thus far. Excellent follow ups and setting up Pauli for deeper diving.

@IanCramer 19/ 16:55 Pauli appears to be talking about #LMHRs. (Talking about how all their other risk factors are low) "... So, yeah, probably they're going to be in much lower risk than the average population is..."

@IanCramer 20/ "But that doesn't mean that their elevated LDL that they also might have wouldn't be a risk factor for them. Now we don't actually have good data on these people..."

This looks like a perfect spot to insert my own commercial break:

https://twitter.com/DaveKeto/status/1195010156766957568?s=20

@IanCramer 21/ Yes! Pauli mentioned he checked into the 7.5k population he was working with for LMHRs and found just 65. But I'm happy he looked. :)

@IanCramer 22/ [Pausing until later. Need to connect for a dinner appointment]

@IanCramer 23/ 34:32 Ian makes the important point, "We shouldn't be making diet and lifestyle decisions based on the exceptions- those people who do smoke and drink like a sailor and live to be a hundred." -- definitely agree!

@IanCramer 24/ 53:43 -- I *love* this point Pauli makes: "The measurement error in diet is much bigger than the measurement error of your blood cholesterol. You can misremember stuff and you can misrecord stuff, but your blood doesn't. So for me, in my world, I deal with the blood markers..

25/ ... "It's more robust and in that sense, I'm much more comfortable handling that kind of data -- than the kind of data you can get from these dietary records." 👈 So, so, so agree with this.

26/ @IanCramer "I think that's extremely healthy to reexamine existing beliefs, and I want to say I fit into that camp. I am discouraged by the echo chambers -- in particular on Twitter -- but just everywhere..."

27/ ... "I'm discouraged by people who won't listen, by people who are closed minded and one of the points of this podcast is to challenge people's beliefs and to put a bug in people's ears and get the cogs turning in people's heads that there might be a better way...

28/ "... and there might be another way, and that there might be better evidence out there. So just think about it. And if you hear it from me, and if you hear it from 5 or 10 other sources over the next couple of years or couple of months, maybe there's some truth to it."

29/ "So all I encourage people to do is to just keep an open mind and continually learn over time."

People who follow me know just how strongly I would agree with that.

30/ At a little before the one hour mark, Ian asks Pauli what would change his beliefs, and Pauli discusses if an animal model had none to nearly no lipoproteins (particularly ApoB-based) and they still developed atherosclerosis. FWIW, I don't think this would ever happen...

31/ We already know people with abetalipoproteinemia and familial hypobetalipoproteinemia have nearly no atherosclerosis. The key question is whether it is comparable to a macrophage in the sense it is part of an immune response to whatever initiates it, or the initiator itself.

32/ Pauli goes into the value of genetic studies. "Now these studies, they are completely free of environmental confounding." -- Given what I've learned thus far, I feel that's not entirely the case...

33/ Certainly there's lots of genetic commonalities regionally -- and given that, there's some potential environmental influences common to that environment that could affect exposures toward outcomes. Not at all claiming this is at high magnitudes, just potentially relevant.