Discover and read the best of Twitter Threads about #LMHRs

Most recents (24)

1/ 🚨New N=1 Experiment: #IsItSaturatedFat🚨
🙏retweet🙏

Yes, I'm doing a new N=1 -- and it's going to be a biggie!

My good friend and colleague, @DrNadolsky completed his recent #MakingLMHR experiment concluding the added 2 sticks of butter as the reason for his LDL increase. Image
2/ He's already conceded he's left out all the context on aiming for #LMHR profile, the relevance of RER, and the #LEM (so no need for people to keep pinging me on the IG video). I've chatted with him privately and we'll leave it at that. 👍

3/ However -- this actually affords us a huge new opportunity.

@DrNadolsky's claim isn't just his own, it's just about everyone else's outside the low carb community.

Simply stated: high #LDL #cholesterol seen in #LMHRs is predominantly due to high consumption of saturated fat.
Read 6 tweets
1/ I want to give huge props to @DrNadolsky for doing this #MakingLMHR experiment!

Yes, I know some of my followers may be blocked -- so I'm including an image as well.

If you're interested in how this experiment came about -- read on... 🧵 Image
2/ We've had an ongoing debate on how much (or little) #saturated fat consumption is responsible for high #LDL #cholesterol levels we typically see for #LMHRs.

Whereas I (we) believe #LEM to have greater relevance overall.

Which led to the experiment👇
3/ Could @DrNadolsky emulate the #LMHR phenotype while *not* being fat adapted? (or at least, to get his #LDL #cholesterol that high?)

He consumed two sticks of butter a day to test this! 🧈🧈

Yes, the experiment went more toward my prediction, so alas, I won't be flying there.
Read 7 tweets
1/5 This is BIG & I've really been looking forward to it. @DrNadolsky will be looking to see if he can reach a #LMHR phenotype while not being low carb or keto (or at a minimum, increase LDL-C to 200)

In short, can high consumption of saturated fat w/o being fat-adapted = #LMHR?
2/5 There's a bit of back-and-forth that originated this experiment which you can read about here 👇

And yes, this could literally result in my flying to him to confirm results directly with advanced bloodwork & RER (Respiratory Exchange Ratio)

3/5 But more importantly, this gets to a very common assumption regarding #LMHRs -- that their phenotype can be mostly explained by higher consumption of saturated fat.
Read 5 tweets
1/ New video by @NutritionMadeS3 which I'd like to retweet for added discussion.

There's a layperson-friendly section in it that does a great job of illustrating the existing expectation of:

(1) LDL/ApoB Exposure Size
X
(2) Time
=
Rate of Plaque Development
2/ Using "mg-years" (much like "pack years" with cigs), one can quickly figure out what state of cumulative exposure they'd be at.

Gil's graph in video was similar to the one I tweeted on last week 👇

And indeed, this is the convention of exposure x time
3/ To be sure, I'd echo @NutritionMadeS3's qualifier in the video that this is expected at a population level. So the exceptions don't prove the rule (in either direction).

Hence the enormous importance of studying those with extremely high LDL/ApoB at a population level...
Read 8 tweets
1/ I'd love to take an opportunity to expand on this important topic, and if I may, suggest something important to watch for with some newly emerging data.

To @MichaelMindrum point, I too believe the #ApoB will demonstrate higher association with #ASCVD than #LDL #Cholesterol..
2/ But to be sure, ApoB can be best represented as:

(1) Non-LDL ApoB lipoproteins
- and -
(2) LDL ApoB lipoproteins

The first category is predominantly chylomicrons, VLDL, and IDL -- which associate very highly with ASCVD.
3/ You can think of category (1) as "Triglyceride Rich Lipoproteins" (TRL, aka "remnants") and category (2) as "Triglyceride Poor Lipoproteins" (TPL)

The population of #LMHRs have extremely high levels of ApoB. But this pattern is a mix of very *low* TRL and very high TPL.
Read 6 tweets
Design a VLC diet that is low in fiber with the goal toward reaching a low respiratory exchange ratio on a cohort of lean, fit athletes (but no other exercise confounding like resistance training or diet confounding like meds/sups, etc).

I’d likewise bet big majority = #LMHRs
Full disclosure - @DrNadolsky and I took to some of this discussion via direct texting. However, it did lead me to a good question that I decided to turn into a poll out of curiosity...
1/2 Another great prop bet @DrNadolsky and I were discussing:

He proposed he could emulate the #LMHR phenotype by consuming a lot of butter and coconut oil while not keto and fat-adapted (thus, high RER). I'd predict the opposite.
Read 4 tweets
1/ Two weeks ago we released our paper on the #LipidEnergyModel (#LEM) along with our video abstract for it. I'm pleased to say it has led to many great connections and expanded discussion.

I'm going to recap on a lot of these in this thread. 🧵 ...

2/ First and foremost, thanks to everyone for their extraordinary support in retweeting our announcement, sharing our paper, and letting researchers know of this model.
3/ As we state many times (including within the video abstract), this model doesn't describe all possible influences on cholesterol levels. For example, other things can impact LDL-C such as M/PUFA-to-saturated fat composition, fiber, genetics, medication, etc.
Read 9 tweets
1/Last weekend at @MetabolicSummit was incredible. Really fantastic speakers and guests discussing metabolism research around microbiome, circadian cycles, muscle mass and longevity (shout out @DrRagnar) and yes, even #LMHRs got lots of airtime (props to @bschermd & @JaimeSeeman)
2/ Wonderful to catch up with so many peeps, like the incomparable @TuitNutrition, @bschermd, @LuciaAronica, @ChrisPalmerMD — and the @DietDoctor team, @tednaiman, @LowCarbRD, @DrEenfeldt, & @bschermd.
3/ Also, the Gala event Saturday night was bitter sweet opening with a recent, yet very inspiring interview from @DrSarahHallberg before her passing, but ending with a packed dance floor and music to finish the night.
Read 4 tweets
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/ A lot of times polls like these are more interesting for the talk they generate than even the results themselves.

Here are a few featured comments and my added thoughts...
2/ A lot of people wanted greater specificity on what I meant by "rich" -- I left this more to the reader's interpretation. IMO, I'd have thought this would be in a highest quantile, such as top 1/3rd or 4th of typical aggregate diet.

3/ @MichaelMindrum mentioned the poll results might skew a bit too much toward expectation of SFA not causing CVD given those likely following my account -- I don't disagree.

Hence my interest in direct study on health conscious populations consuming high SFA (like many #LMHRs)
Read 5 tweets
📊Polls ahead of #KetoSaltLake

Poll (1/4)
Lean Mass Hyper-responders (#LMHRs) are defined by:

+⬆️#LDL #Cholesterol at 190mg (5.17mm) or higher,
+⬆️#HDL-C 80 (2.07) or higher &
+⬇️#Triglycerides of 70 (0.79) or lower

In your opinion, cardio risk level of this profile is likely
Poll (2/4)
Many demonstrating the #LMHR phenotype (but not all) consume a diet...

High in animal protein
High in red meat
High in saturated fat

In your opinion, if we were to further stratify the #LMHR population to those with the above diet, their cardio risk level would be...
Poll (3/4)

When did you first hear of the Lean Mass Hyper-responder profile?
Read 5 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/ Heard enough Lipoprotein Lipase (LPL)?

The tl:dr -> There's more selective control with fatty acid exchange in tissues than we fully understand... but we have a lot more we've learned recently...

#LipidEnergyModel @nicknorwitz

sciencedirect.com/science/articl…
2/ "Preferential uptake of FAs into high demand tissues such as the heart, muscle and brown adipose tissue cannot be achieved by non-specific uptake, which would acutely distribute FAs equally into all cells."

- Translation: there's some selective trafficking going on here.
3/ "A second uptake process modulated by activity of capillary lipoprotein lipase (LpL) involves FAs derived from triglyceride (TG) rich lipoproteins (chylomicrons and very low density lipoproteins." (VLDL)

- Yes, lipoproteins + LPL = hydrolysis of TG to cells
Read 11 tweets
1/6 Yes -- this article is over 3 years old now and I then presented on Remnant Cholesterol (RC) at LC Denver earlier that year.

In rereading this article, there are a few things I'd update -- but the general focus on systemic outcome relevance still holds...
2/6 A more updated article on this, along with further thoughts, can be found here: cholesterolcode.com/thoughts-regar…
3/6 If you read nothing else, check out this section from the article, and why I'm so vocal about *not* looking only at #ApoB (which lumps non-LDL and LDL) together.

Again -- and with emphasis -- this is part of the larger hypothesis. But all the more reason to research it...
Read 6 tweets
1/ #ListeningThread

Two fantastic intellectuals, @robbwolf and @lipoprotein, chatting about lipids, cardiovascular disease, and #LMHRs

Good podcast for my evening walk — might add some thoughts here…
2/ Wow, in the intro Rob mentions Bill having discussed LMHRs with me (and yes, we’ve had many great chats on the topic). Where he agrees, and where he disagrees. To be sure, I have a bit of an advanced preview on what that will likely be. ;) but I’m excited to hear it in the ep.
3/ 28:30 Bill: I think Dave Feldman has probably helped more than any one person in giving disability and how radically our bodies can change [lipid levels] in just days… So yeah, you can actually influence these results quite a bit in a 3 to 5 day period of time…
Read 28 tweets
1/ Thank you for the invitation, @chadinabhan.

I've now listened to the episode and was a bit surprised at a few points, but also less so with others.

Cholesterol is a very emotionally charged topic, and understandably so...
2/ For me, this journey started 6 years ago with alarmingly high total and LDL cholesterol following my going on a ketogenic diet. I became obsessed with trying to understand why and begin reading everything I could on lipidology...
3/ I found through a series of experiments there was quite a bit of change I could induce based on dietary patterns. As I developed and executed this "citizen science" research, I turned it around back to the community to hopefully help us in advancing this important topic.
Read 25 tweets
1/ This would be a good opportunity to clear the air on a few things...

Per @DrNadolsky's tweet, we don't know everything we want to know about #atherosclerosis. Almost everyone would agree it is multifactorial, and most of Med would ascribe the central risk driver to LDL/ApoB..
2/ If you see your LDL rise on a #keto/#lchf diet and you're uncomfortable with this, here's a thread I made for that 👇

3/ In the mean time, @DrNadolsky, @DrRagnar and I are literally in the final stages of IRB (knock on wood) to get clinical data via CitizenScienceFoundation.org <obligatory plug>

Clinical data is almost always more valuable than anecdotal data (assuming good design, reputable team)..
Read 7 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
1/ Reminder: "Lean Mass Hyper-responder" is literally defined as a combination of LDL ≥ 200, HDL ≥ 80, and Triglycerides ≤ 70.

In other words -- by definition -- #LMHRs are not hypertriglyceridemic (high triglycerides). They are the opposite. (See CholesterolCode.com/lmhr)
2/ For example, in the first of this case series a woman is identified as hypertriglyceridemic (triglycerides of 1109). This is if 15 fold higher than the TG max cap of #LMHR.

lipidjournal.com/article/S1933-…
3/ Moreover, we actually addressed this particular case of hypertriglyceridemia in our Letter to the Editor of this very case series. In fact, it's how we set up the question on what to consider when triglycerides are low instead

Read 4 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

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