Discover and read the best of Twitter Threads about #LMHRstudy

Most recents (20)

1/ Always honored to have your added opinions, @Lpa_Doc and I'll again mention I'm a tremendous fan of your work (and the #OxPL assay, btw)

The #LMHR phenotype is potentially providing a new window of investigation into lipid metabolism, but its high LDL risk level is unclear...
2/ ... Hence the importance of the #LMHRstudy (still recruiting, btw -- see LMHRstudy.com for details)

In the mean time, we regularly and often emphasize everyone should work with their doctor and understand the guidelines recommend against high cholesterol...
3/ ... There are many like this pt who are in the unusual position of having a severe medical condition that appears to be uniquely resolved through a very carb restricted diet.

With respect, the patient didn't immediately refuse any form of treatment...
Read 6 tweets
1/ #Study #MegaThread

A new study dropped with a trove of data I've long waited for around #CCTA/#CAC scans and #LDL #Cholesterol

✅ >23k studied (!)
✅ Largest sample of CCTA w/ ≥190 #LDL to date (!)
✅ Very uniform study population

Let's unpack...
jamanetwork.com/journals/jaman…
2/ First, be sure to check out this short thread from the lead author, @MaBMortensen.

2 quick notes:
a) While there'll be lots of data appreciated by LDL skepticism, @MaBMortensen maintains LDL-C is still "an important causal RF"
b) Usual epi caveats, etc
3/ Okay, so if you've followed me a while, you know just how incredibly thankful I am of studies that seek to avoid common risks of selection bias (Even if entirely unintended).

This study had the distinct advantage of categorically scooping its population directly...
Read 18 tweets
1/ A very busy time

But in this late moment of calm before the weekend, I'm finding myself truly humbled that our #LMHRpaper is finalized and has crossing so many interested eyes.

I hope many will agree with us this phenomenon is well worth researching.

cholesterolcode.com/our-paper-on-l…
2/ Via @nicknorwitz: "... this paper has stimulated vigorous discussion, risen to the top of its journal for all time reads, and is among the top 15 trending papers across all American Society of Nutrition associated journals for the year 2021." nutrition.org/15-trending-nu…
3/ There's quite a bit more work in the pipeline from the many great collaborators I have the honor to be working with. We're passionately working on a #LipidEnergyModel paper, the #LMHRstudy (currently underway), and a couple other projects I can't announce just yet...
Read 5 tweets
1/ If you want to hear a great discussion on the #LMHRstudy from my colleague,@DrNadolsky (who is most definitely pro-#LDL #Cholesterol lowering), I highly recommend this podcast that just dropped via @Plant_proof.

I'll add just a few quick thoughts...
2/ Firstly, this may be the most I've heard myself talked about in a podcast I wasn't in (😂 weird, but understandable given the context).

But while certainly critical in many respects, I felt both @DrNadolsky and @Plant_proof provided a lot of good context...
3/ @DrNadolsky bring up my oft-repeated phrase, "cautiously optimistic" [in the context of higher LDL/ApoB as a seemingly resulting from metabolic fat-adaption]

Worth repeating that mine is a hypothesis and should be treated as such, hence the "cautious" part of the phrase...
Read 8 tweets
1/ This is especially important timing.

As many of you know, we're conducting a study on #LMHRs (link later in thread) who not only have extremely high #LDL #Cholesterol, but many (likely most) have diets quite contrary to this advice by the @American_Heart.

Let's unpack...
2/ First, and most importantly, we do not know what the outcome of this prospective study is. So while I'll be outlining commonalities we observe with #LMHRs, this isn't an explicit endorsement of the diet nor any altered lipid levels as a result.

With that said...
3/ We have a lot of data between our standing survey, submissions to CholesterolCode.com, and CC and LMHR Facebook groups (7.7k and 7.5k members, respectively).

Diets are often:
1) Low to no fruits & veg
2) Low to no grains
3) High animal protein
4) Low in plant oils
Read 6 tweets
1/ Wow -- it's been quite a week! I announced the #LMHRstudy six days ago. And in case you missed it -- visit here for more details:

CitizenScienceFoundation.org/study

I'm going to provide some updates and answers to frequent questions of the last several days...
2/ "Dave, can you get me in the study?"

No! You have to contact Lundquist directly through the proper channels and they will decide based on the study design whether you qualify as prescribed by existing eligibility criteria we all determined in advance.
3/ While myself, @DrNadolsky and @DrRagnar developed the protocol in collaboration Lundquist, we in no way can (or should) influence any decision making regarding individual considerations -- and that's a good thing. We want this study as fair and objective as possible.
Read 7 tweets
1/6 I'd like to both retweet and add on to @NutritionMadeS3's point here...

Again, and with emphasis, my position is one of cautious optimism. That's an explicit acknowledgement of uncertainty, even if I have a leaning toward the positive in this context...
2/6 I discuss this at length in 13-15 of my pinned tweet

Hence the importance of #LMHRstudy

I'd hope this were self-evident, but if I were completely certain high LDL + high HDL + low TG = low risk in fat-adapted context, there'd be no effort for a study
3/6 I've chatted with @NutritionMadeS3 and others on evidence I consider very compelling regarding the connection of health and illness for lipid metabolism and their impact on lipid profiles. But I likewise stress we'd be better served with prospective data in this context
Read 6 tweets
1/ Very cool experiment and thread by @ScepticalDoctor who did a more #PlantBasedKeto and saw low #LDL #Cholesterol given high MUFA/PUFA relative to sat fat, along with high fiber (which supports my prior thread)

If looking to keep LDL low, this might be worth considering...
2/ As per my various tweets before this one on the topic, and not to beat a dead horse, I feel it is too often "low carb vs plant based" is often assumed the latter *must* be high carb -- thus, "low carb, animal-based vs high carb, plant-based"

... This is a false dichotomy...
3/ There are definitely some of us who are, as I like to say, "cautiously optimistic" with regard to higher LDL as appears to be resulting from metabolic fat adaptation in the context of higher sat fat, lower MUFA/PUFA and low to no fiber. But this risk degree is uncertain...
Read 6 tweets
1/ I'd like to put a lot of misconceptions to bed on this topic -- so let's unpack...

I personally believe the coming #LMHRstudy will be neither one of these:

1) A categorical end to the lipid hypothesis
2) Completely meaningless
2/ If it seems like there's a wide spectrum of possibilities between those two endpoints, it's because there is

Sure, I do think this may end up testing if the lipid hypothesis can be taken as "dose-dependent, log-linear" in every context. But that's not testing it categorically
3/ For example, it could well be we observe a very low progression of plaque in LMHRs for reasons none of us are aware of yet, but of which don't apply to those with atherogenic dyslipidema in original sense (thus, mixed outcome, new mechanistic aspects yet to be determined, etc)
Read 11 tweets
1/ Watching this episode of @PeterAttiaMD's podcast with @garytaubes...

On "Pathological Science"...

Taubes: “One of the defining characteristics of pathological science is — people commit themselves publicly to a result based on premature evidence…”
2/ “…So it’s not ironclad, they haven’t locked it down, there’s still a chance they could be wrong and they don’t understand the likelihood of that chance, no one ever does until you get very good at this when you realize that chance is enormous.”
3/ “And so once you go public, science is supposed to be hypothesis and test, right? You’re supposed to rigorously test your hypotheses and ideally you’re trying to prove that you’re wrong..."
Read 10 tweets
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. :)
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…
Read 13 tweets
1/ This new MR study by @mendel_random, @mvholmes, et al makes use of UK Biobank data and determines #ApoB increases risk of #AllCauseMortality, and even #T2Diabetes

This is actually relevant timing as we are rapidly approaching the #LMHRstudy. sciencedirect.com/science/articl…
2/ If you didn't already know, "Lean Mass Hyper-responders" (#LMHRs) would be considered hypercholesterolemic, with this resulting from being very low carb (typically #keto), and are often lean and/or athletic.

(You can read more on this phenotype at CholesterolCode.com/lmhr)
3/ Setting aside why this population exhibits this (see #LipidEnergyModel for more), the most important question is whether they are at risk.

This MR study builds on the existing conventional expectation that they are, and no less in a dose-dependent manner...
Read 6 tweets
Presentation Polls
—————————-

1/ Your current LDL cholesterol is:

(All units are mg/dL)
2/ Your current HDL cholesterol is:
3/ Your current triglyceride (TG) level is:
Read 9 tweets
1/ I want to tackle this question head on because it needs to be discussed -- particularly in why the #LMHRstudy is needed.

I now know a number of #LMHRs with long term data that looks very encouraging. Does that prove it's a safe profile? No. This is small, selected sample..
2/ Would a handful of #LMHRs with deleterious outcomes prove it's a dangerous profile? No -- for the same reason.

We don't which are the outliers.

As the known population of these now number in the thousands, a statistician would ask, "what the odds you *wouldn't* see both?"
3/ Those supporting this profile could point to the many showcasing excellent results. Those opposed could point to the few demonstrating the opposite.

Each feeling their examples represent the central mean and others' the outliers.
Read 4 tweets
2/ I love that Alan Flanagan kicked off with distinction question re bio markers.

“System Biomarkers in the causal pathway. Systemic biomarkers that can report on the overall picture”
vs
“Biomarkers of disease progression”
...
3/ “... It seems to be in the wider conversation a lot of these are often conflated to a degree. Or there is misplaced emphasis placed on a particular marker...”

I couldn’t possibly agree with this more!
Read 12 tweets
1/ For a very layperson-friendly video on conventional view of #LDL / #HDL #Cholesterol, and #ApoB, I highly recommend this one from @NutritionMadeS3

It's very visual and IMO fairly true to the more specific position of mainstream lipidology...
2/ Love his opening: "why is this topic so confusing? well, for starters scientists are horrible at coming up with names...there's LDL...and LDL cholesterol and they're different things....but a lot of people call them both LDL....and then there's HDL, VLDL..." (trails off)
3/ He's 100% right. It's why it's so hard to convert this for the lay audience. Lipidology could use a terminology upgrade.

For example, how did "Chylomicrons" manage to get a special exception to the "-DL" acronym party? (Only fellow lipophiles will get that joke... 😐)
Read 7 tweets
1/ Okay, I've been getting lots of pings regarding @DBelardoMD appearing on @RealDoctorMike, particularly given discussion earlier in the video with regard to LDL-C and CVD.

I'll do a reaction thread for now, but I'd like to keep it respectful, ofc...
2/ *First, whether ur a @DBelardoMD fan or not, I have to emphasize I respect anyone willing to move against the grain of their community for where they feel the evidence takes them. While unrelated to lipids, she's endured a lot of unpleasantness for a principled re CVD reversal
3/ 2:08 @DBelardoMD: "Nowadays you want to get your LDL cholesterol as low as possible for cardiovascular risk prevention. So, primary prevention versus also secondary prevention."

->Of course, neither this or statements like these are controversial by conventional med standards
Read 12 tweets
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
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...
Read 7 tweets
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

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