1/ So I’m finally getting around to listening to the last episode of @ethanjweiss’s podcast, #BestKnownMethod, this one featuring @skathire. Because my last tweet-as-I-listened format has gotten lots of requests, I’ll do so here as well. Starting.... now
2/ After some biography, they are getting into the genetics, and @ethanjweiss adds a helpful explainer at 29:00 to help the lay audience (I’m only slightly less lay, but I still have plenty left ;) ). I always love when podcasts can do this.
3/ At 34:26 @skathire discussing the issue with epidemiology determining causation, he points out often X doesn’t cause Y, often there’s a third factor that can influence both (call it Z) creating the association. I agree.👌 But to be sure, this applies beyond epis, of course.
4/ at around 39:26 “Not just one gene... almost any gene that changes LDL cholesterol” [to high results in more heart disease, and any gene that naturally lowers results in less.] ...
...Probably everyone who knows me well — knows what follow-up question I’d want to ask
5/ Yaaaaay, at 51m @ethanjweiss is opening the subject of hyper-responders...
6/ 51:40 @skathire says (paraphrasing) The evidence is pretty clear every 40 mg/dL lowering of LDL you get a 22% reduction in risk and we can flip that for hyper-responders going upwards. “that relationship, that slope of LDL change and heart attack disease risk is pretty firm”
@skathire 7/ *** I'm taking the rare step of deleting the last tweet of Sek's quote (I almost never delete tweets). This is for intellectual honesty reasons as @skathire's initial statement is further qualified a few minutes later where he begins, "I should be more precise..."
@skathire 8/ Shortened version: @skathire feels confident LDL lowering will reduce risk, all else being equal. But he likewise concedes there's a lot of unknowns regarding CVD risk benefits regarding diet, particularly with weight loss.
@skathire 9/ 58:12 @ethanjweiss goes into another explainer here. I'm really digging these things. He's talking out correlation and causality...
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First, let me say that data on this has been a bit limited. But *IF* we do ultimately confirm there are more ApoB-48 (B48) than ApoB-100 (B100) in ASCVD plaque, it would be a very big deal.
Let's unpack...
2/ First, thanks to @TuckerGoodrich for pinging me on these pubs and pressing the discussion.
But also credit to @CaloriesProper on tweeting this a couple years ago (I missed it then)
To understand why this would be so important if true, some review...
3/ B48 and B100s are the major proteins on chylomicrons (CMs) and VLDLs, respectively.
CMs mostly carry lipids from the small intestine to the bloodstream (lipids consumed), VLDL mostly carry lipids from storage; predominantly from adipose stores.
#Me: Why would triglyceride rich LDL particles be more atherogenic than triglyceride poor LDL particles?
#ChatGPT: Triglyceride-rich LDL (low-density lipoprotein) particles are more atherogenic (i.e., more likely to contribute to the… twitter.com/i/web/status/1…
2/
#Me: Couldn’t it also be possible that triglyceride rich LDL are ultimately the result of metabolic dysfunction and that better explains its association with atherosclerosis?
#Me: Is it possible that almost the entire amount of atherogenesis associated with high triglyceride rich LDL is due to dysfunctional lipid metabolism and the diseases that result in these profiles rather than the LDL particles themselves?
1/🧵 I'm definitely a fan of both @DominicDAgosti2 and @DrRagnar (obviously), so I was excited to see them chatting about #lipids, #LMHRs, and Dom's consideration of increasing carbs to lower his #ApoB
3/ When chatting with Dom in SD last year for dinner, he mentioned focusing less on maintaining such a sizable muscle mass as he typically does, and I predicted he'd likely see his LDL/ApoB as considerably higher with this change if still #keto. This podcast appears to confirm...
But I also know many people in my own family who have struggled their whole lives to lose weight and assume if they don't have this near instant drop to their goal weight like <fill in the blank success story> then they are doing it all wrong...
... I can't tell you how many times I point out truly new, record-setting successes with people I know personally -- but it's their own record, their own health journey.
But they often can't see it because they hear they "won't be hungry anymore on <fill in blank diet>"...