1/ Long running thought exp'nt:

If a drug did many of the same things with one's lipid profile as a #LowCarb diet, particularly decreasing triglycerides while increasing #LDL #Cholesterol:

1) Would it reduce ASCVD risk?
2) And if so, would it be more acceptable than #LowCarb?
2/ If you haven't heard, SGLT2 Inhibitors have recently emerged and have been gaining a lot of popularity. Data thus far shows they typically:

1) Decrease TG levels
2) Increase #LDL #Cholesterol levels
... yet...
3) Reduce risk for cardiovascular disease
3/ Naturally, that has the attention for those of us interested in how triglyceride trafficking and turnover could be relevant to #LDL increasing for what may turn out to be non-pathogenic reasons (kinda my focus ;) )

CholesterolCode.com/model

But wait -- it get's better...
4/ Investigations with animal models lend even greater weight to the proposed mechanism of the model:

"... due to reduced clearance of LDL from the circulation and greater lipolysis of triglyceride-rich lipoproteins."

ncbi.nlm.nih.gov/pmc/articles/P…
5/ So while I know they'll be politics as to whether high LDL due to Rx should be more preferable to high LDL due to fat-adaptation, I'm *especially* interested in how SGLT2i operates in similar fashion in demonstrating what we've hypothesized with the model...
6/ If the reason for higher LDL is due to greater relative lipolysis and turnover of its precursor as VLDL, then this may further support the #LipidEnergyModel -- and even give a clue on what we might see with CVD risk outcome in this regard.
7/ Ofc, #LMHRs typically have #LDL substantially higher than trial populations for SGLT2i. Thus, if true that #LDL is independently pathogenic, it would presumably exceed benefit as per the existing medical expectation.

<Insert obligatory reminder of our coming #LMHRstudy here>

• • •

Missing some Tweet in this thread? You can try to force a refresh
 

Keep Current with Dave Feldman

Dave Feldman Profile picture

Stay in touch and get notified when new unrolls are available from this author!

Read all threads

This Thread may be Removed Anytime!

PDF

Twitter may remove this content at anytime! Save it as PDF for later use!

Try unrolling a thread yourself!

how to unroll video
  1. Follow @ThreadReaderApp to mention us!

  2. From a Twitter thread mention us with a keyword "unroll"
@threadreaderapp unroll

Practice here first or read more on our help page!

More from @DaveKeto

16 Mar
1/ Great new thread by the incomparable, @Lpa_Doc -- covering a number of my favorite topics.

Read his thread and return for my added thoughts...
2/ Vilhjalmur Stefansson is a well discussed explorer among the #LowCarb and (of course) #Carnivore communities.

But even more interestingly, he may have been the first #LeanMassHyperResponder of record*

(* Kinda -- as Sam notes, we didn't advanced lipid panels then)
Read 6 tweets
15 Mar
1/ How much does "Dietary Cholesterol" impact blood cholesterol levels?

This has been making the rounds lately and I have an experiment from 2018 is key to this question 👇

Remember the "White Bread and Processed Meat" experiment? cholesterolcode.com/the-tandem-dro…
2/ If you've followed me a while, you know I believe it isn't the actual ingestion of cholesterol on #LowCarb that has a big impact on serum levels -- it's predominantly the trafficking of fat. (See CholesterolCode.com/model)

But this is actually a very testable distinction...
3/ All we need is an experiment where I consume a lot of (1) low fat food that still (2) has ample amounts of cholesterol.

Thus, the "processed meat" side of the experiment is key if it has a decent amount of cholesterol -- and it does.

For example 9/21/18 I ate the following..
Read 8 tweets
13 Mar
1/ Thread ➡️This is a good spot to remind everyone why @DrNadolsky, @DrRagnar and I are doing the #LMHRstudy

(@nicknorwitz, I'm going to use you as an example, if you don't mind)

Nick has an LDL-C of 521, well into range of Homozygous Familial Hypercholesterolemia (HoFH)...
2/ FH, particularly HoFH is highly associated with atherosclerosis and is considered a substantial risk.

Cases of HoFH are extremely rare, but are considered a cornerstone of the lipid hypothesis as many with LDL-C levels (comparable to Nick's) demonstrate CVD as children...
3/ Brown and Goldstein have seminal work on this topic.

In particular, this is worth reading in regard to this subject: ncbi.nlm.nih.gov/pmc/articles/P…

(Warning: this includes many graphic images of xanthomas, which are more common with high LDL FH)
Read 9 tweets
7 Mar
1/ 🤔Thought Experiment Thread🤔

The five assessments of Metabolic Syndrome are:
- High waste/hip
- High TG
- Low HDL
- Elevated BP
- Elevated fasting glucose

👆3 or more, you have MetSyn.

But what if you had just one of them, but at the top 3% for the general population? Image
2/ For triglycerides, I have some numbers handy from NHANES...

Hypothetical: You had *no other* cardiovascular risk factors save triglycerides in the top 3% of the general population (above 339 mg/dL)

What would you speculate your risk level for CVD is?
3/ Same with HDL...

Hypothetical: You had *no other* cardiovascular risk factors save HDL in the lowest 3% of population (below 30 mg/dL)

What would you speculate your risk level for CVD is?
Read 8 tweets
7 Mar
1/ Really great thread by @Lpa_Doc in response to @ethanjweiss.

Read completely before returning here for my added thoughts...

[Warning: this one will get a little geeky]
2/ Per @Lpa_Doc's (2) and (3) in the thread, when we have "normal" TG levels (guidelines would say < 150, I prefer < 100) then most cholesterol in ApoB-containing lipoproteins (ApoB-Lp) are in LDL and there's little VLDL-cholesterol...
3/ But where TG is high, there's more utility in looking at ApoB given it lumps remnants (VLDL/IDL) with LDL.

-- But IMO, that's also the problem. We want to disentangle where remnant association is much more relevant than LDL association...
Read 6 tweets
5 Mar
1/ I’ll be interviewing @KetoCarnivore soon. In preparation, I watched this talk of hers from 2019 that I found very interesting...
2/ She provides some counter opinion analysis regarding both simplified metrics of “nutrient density” and the protein leverage hypothesis (ie @tednaiman). Or more specifically, the challenge in these approaches having potential bias that isn’t easily apparent...
3/ To be sure, I don’t have a very strong opinion myself in this area as I tend to focus more on lipid trafficking (and generally try to avoid the nutrition debates overall).

Moreover, I’m still plotting to do @tednaiman’s P:E diet as an experiment soon along w/bloodwork...
Read 5 tweets

Did Thread Reader help you today?

Support us! We are indie developers!


This site is made by just two indie developers on a laptop doing marketing, support and development! Read more about the story.

Become a Premium Member ($3/month or $30/year) and get exclusive features!

Become Premium

Too expensive? Make a small donation by buying us coffee ($5) or help with server cost ($10)

Donate via Paypal Become our Patreon

Thank you for your support!

Follow Us on Twitter!