Many medical professionals (like my good friend and colleague, @DrNadolsky) feel strongly that #LowCarb-ers may be acting very recklessly by allowing their #LDL#Cholesterol to be much higher than the guidelines allow.
Certainly if "diet induced" high LDL is the equivalent to genetically high LDL, such as those with #FamilialHypercholesterolemia (FH), then there should be likewise rapidly progressing #atherosclerosis.
3/ "The sine qua non of FH is severe elevation of total and LDL cholesterol levels." jaoa.org/article.aspx?a…
Often heterozygous FH is considered where LDL is 190 to 500 mg/dL, with homozygous being above 500.
4/ Indeed, there are key symptoms they may arise in the low carb community related to high cholesterol-- the most relevant being "tendon xanthomas"
"Tendon xanthomas are a classic pathognomonic physical examination finding, detected in approximately 20% to 40% of those with FH."
5/ I won't link a picture here, but you can google "tendon xanthomas" for examples.
(Note these are different than xanthelasmas which can occur around the eyes/eyelids, but are less specific to FH -- where tendon xanthomas are very specific)
6/ Given children with homozygous FH can get tendon xanthomas at age 2 or 3, and given the lipid hypothesis considers "LDL burden" to be dose dependent and log linear over lifetime exposure- these symptoms should be showing up at very high rates for low carb hyper-responders soon
7/ Which is all the more reason to take Computed Tomography Angiography (CTA) scans in a clinical trial as soon as possible -- which is our central measurement for the study.
CTAs can display powerful, high resolution geography of the cardiovascular system.
8/ And given the effect size of "Lean Mass Hyper-responders" (LMHRs) where LDL is often well above the guidelines (>190 mg/dL -- with many in the 300s, 400s, 500s or more), we should be able to observe the same rapid progression of atherosclerosis we see with FH in just 1 year.
9/ To emphasize -- if you believe low carbers are being too cavalier with their high cholesterol -- help fund this study to bring this data back to them ASAP.
This study could potentially give notice to everyone on low carb who might need to take steps to lower their lipids.
10/ Conversely, if you yourself are low carb with high cholesterol and believe the data will show low to no risk, you should be just as motivated to get the evidence specific to this context.
In short -- help us get the data that's relevant to you.
11/ As of this thread, our funding sits at $86,472.00 on our way to $100,000 -- where we have an anonymous donor set to match with an additional $100,000 when we reach the goal. 🚨
Which is to say -- we're very, very close to having our goal of $200k to meet our base funding.
12/ There's been more than enough debate around this topic without the clinical data to its context. If many low carbers are going to maintain higher LDL regardless of the guidelines, we should capture this data ASAP to confirm its efficacy.
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>"...