Discover and read the best of Twitter Threads about #LMHRs
Most recents (24)
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
If no one minds, I'd like to add some thoughts...
If no one minds, I'd like to add some thoughts...
2/ First -- I'm extremely excited to share @DominicDAgosti2 may be the most notable N=1 I've waited for regarding #ResistanceTraining change & #LDL/#ApoB in a #ketogenetic context
Those who've followed me for a while know exactly what I'm talking about...
Those who've followed me for a while know exactly what I'm talking about...
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...
1/ #Metabolism, #lipids, and #ASCVD
#megathread🧵🧵🧵
Okay, I want to revisit and breakdown my position on this crucial topic and the challenges in communicating it.
⚠️ Get comfortable, as this could get long.
Ready? Let's go...
#megathread🧵🧵🧵
Okay, I want to revisit and breakdown my position on this crucial topic and the challenges in communicating it.
⚠️ Get comfortable, as this could get long.
Ready? Let's go...
2/ First, it's worth reviewing why there's a high level of confidence low density lipoproteins (LDLs) drive atherosclerotic cardiovascular disease (ASCVD)
For an excellent, lay-person video, I recommend @NutritionMadeS3's from a couple years ago 👇
For an excellent, lay-person video, I recommend @NutritionMadeS3's from a couple years ago 👇
3/ Also in the name of arguably the most cited meta-analysis for the Lipid Hypothesis to date:
"Low-density Lipoproteins cause atherosclerotic cardiovascular disease"
This meta combines lines from genetic, observational, and interventional studies.
pubmed.ncbi.nlm.nih.gov/28444290/
"Low-density Lipoproteins cause atherosclerotic cardiovascular disease"
This meta combines lines from genetic, observational, and interventional studies.
pubmed.ncbi.nlm.nih.gov/28444290/
📍Big milestone!📍
The Nov/Dec @LipidJournal just dropped!
🚨Featuring the #LMHReditorial 🚨
via @nicknorwitz et al
It focuses on #LMHRs, both in consideration of their high #LDL and an urgent call for expanded #research.
Why is this important?... /1
doi.org/10.1016/j.jacl…
The Nov/Dec @LipidJournal just dropped!
🚨Featuring the #LMHReditorial 🚨
via @nicknorwitz et al
It focuses on #LMHRs, both in consideration of their high #LDL and an urgent call for expanded #research.
Why is this important?... /1
doi.org/10.1016/j.jacl…
2/ Certainly the biggest impact is bringing this phenotype well into the spotlight.
If you've been following my work from the beginning, you can appreciate just how much energy I've put toward putting this phenotype in front of Lipidologists.
If you've been following my work from the beginning, you can appreciate just how much energy I've put toward putting this phenotype in front of Lipidologists.
3/ But this is understandably a challenge given how much progress on this research has been accomplished outside typical channels ("Citizen Science").
-- Until now.
-- Until now.
🧵1/8 Here's an easy thread for reference on our current papers. 👇👇👇
🔖 Bookmark this!
We cover:
- High #LDL on #lowcarb/#keto
- Lean Mass Hyper-responders (#LMHR)
- The Lipid Energy Model (#LEM)
- And, ofc, our #LMHRstudy underway right now
🔖 Bookmark this!
We cover:
- High #LDL on #lowcarb/#keto
- Lean Mass Hyper-responders (#LMHR)
- The Lipid Energy Model (#LEM)
- And, ofc, our #LMHRstudy underway right now
2/8 The #LMHRpaper was our first describing the #LMHR phenotype
- #LDL #Cholesterol of 200 or higher
- #HDL #Cholesterol of 80 mg or higher
and
- #Triglycerides of 70 mg or lower
Which is actually common for lean, very folks on #lowcarb/#keto folks. doi.org/10.1093/cdn/nz…
- #LDL #Cholesterol of 200 or higher
- #HDL #Cholesterol of 80 mg or higher
and
- #Triglycerides of 70 mg or lower
Which is actually common for lean, very folks on #lowcarb/#keto folks. doi.org/10.1093/cdn/nz…
3/8 Our second paper brings a case report on a single #LMHR with extremely high #LDLc (~500 mg/dL) for 2.5 years, their eating patterns, and current CT angiography.
(⚠️Please note this is a single case report and should be considered anecdotal, ofc) doi.org/10.3389/fendo.…
(⚠️Please note this is a single case report and should be considered anecdotal, ofc) doi.org/10.3389/fendo.…
1/ Alright, let's chat the #NHANES (IV)
As usual, I'll give my caveats this is back-of-the-envelope on data I wrangled via CDC on this expansive dataset -- and it's associational, ofc (observational)
So what are the lipids like for those who live to 100yr in NHANES?
As usual, I'll give my caveats this is back-of-the-envelope on data I wrangled via CDC on this expansive dataset -- and it's associational, ofc (observational)
So what are the lipids like for those who live to 100yr in NHANES?
2/ Remember, these aren't the lipid levels taken *at* age 100+, it's what their levels where at the time of examination 15-20 years prior.
This is very relevant when considering reverse causality given this extreme gap in time for all who were reaching centenarian status.
This is very relevant when considering reverse causality given this extreme gap in time for all who were reaching centenarian status.
3/ First up -- #LDL #Cholesterol.
Yes, 73% of you correctly guessed 130mg/dL is the mean average for these 32 individuals (lipids taken age 85 or earlier).
LDL mean average: 130 mg/dL
0% 25% 50% 75% 100%
72.0 102.5 126.0 154.0 215.0
Yes, 73% of you correctly guessed 130mg/dL is the mean average for these 32 individuals (lipids taken age 85 or earlier).
LDL mean average: 130 mg/dL
0% 25% 50% 75% 100%
72.0 102.5 126.0 154.0 215.0
🧵 New paper on comparing advanced lipid testing (NMR) with body fat (adiposity) - ht @nicknorwitz
High adiposity associates with:
- ⬆️ #ApoB & #LDL-C
- ⬆️ #triglycerides
- ⬆️ levels of all fatty acids
How does this relate to #LEM? Let's unpack... /1
nature.com/articles/s4385…
High adiposity associates with:
- ⬆️ #ApoB & #LDL-C
- ⬆️ #triglycerides
- ⬆️ levels of all fatty acids
How does this relate to #LEM? Let's unpack... /1
nature.com/articles/s4385…
2/ "Adiposity-related hypertriglyceridemia is mainly driven by increased numbers of triglyceride-rich VLDLs (which carry the largest proportion of triglycerides in blood). Concurrently, the cholesterol in these lipoproteins also seem to be higher at higher adiposity levels."
3/ And these next sentences are key -- take special note of the underlined text...
🚨New #LMHR Editorial in JCL!🚨
🙏Please RT🙏
- Cautious consideration for #LMHRs
- Calls for patient-centered approach
- Calls for more research on #LMHRs(!)
AND we raised money from the LMHR community to make this *open access*.
Let's unpack... /1 authors.elsevier.com/a/1g22A6tb2E2O…
🙏Please RT🙏
- Cautious consideration for #LMHRs
- Calls for patient-centered approach
- Calls for more research on #LMHRs(!)
AND we raised money from the LMHR community to make this *open access*.
Let's unpack... /1 authors.elsevier.com/a/1g22A6tb2E2O…
2/ So why is this a big deal?
Two reasons:
For one, this editorial is the first of its kind to gather MDs and PhDs together to help develop a clinical position on the #LMHR phenotype and importance of expanding research around this phenomenon.
That's hard to understate!
Two reasons:
For one, this editorial is the first of its kind to gather MDs and PhDs together to help develop a clinical position on the #LMHR phenotype and importance of expanding research around this phenomenon.
That's hard to understate!
3/ Typically, there have been just two positions on the topic of high LDL on keto, particularly LMHRs.
- Conventional: LMHR *must* lower LDL/ApoB
- LH skeptic: LMHR can ignore LDL/ApoB
This editorial concludes those with high LDL-c/ApoB from keto "should consider" lowering.
- Conventional: LMHR *must* lower LDL/ApoB
- LH skeptic: LMHR can ignore LDL/ApoB
This editorial concludes those with high LDL-c/ApoB from keto "should consider" lowering.
1/ Yes, the topic of a "hyper-response" with high #LDL #Cholesterol (LDLc) on #keto has been coming up a lot this summer, particularly for #LMHRs -- and that's a good thing. More discussion and research desired!
I'll try to unpack the key differences in 3 standing hypotheses...
I'll try to unpack the key differences in 3 standing hypotheses...
2/ Conventional: higher LDLc "hyper-response" (HR) mainly due to higher consumption of saturated fat (SF)
@DrNadolsky hypothesis: HR due to higher SF, but also genetics
Me: HR affected by many things, but generally more influenced by Lipid Energy Model (LEM) than SF or genetics
@DrNadolsky hypothesis: HR due to higher SF, but also genetics
Me: HR affected by many things, but generally more influenced by Lipid Energy Model (LEM) than SF or genetics
3/ Starting with a few key influences we all agree on...
These things likely have a significant detectable increase on LDL compared to reverse:
1) Swapping unsaturated fat with SF
2) Reducing fiber
3) Less resistance training
These things likely have a significant detectable increase on LDL compared to reverse:
1) Swapping unsaturated fat with SF
2) Reducing fiber
3) Less resistance training
1/ Interesting thread via @NutritionMadeS3. I invite everyone to read through his before reading the remaining of mine here below…
2/ naturally, you’re discussing a topic that’s very near and dear to my research, @NutritionMadeS3. I’m certainly very interested in metabolic health as it relates to lipid profiles — particularly the “triad” of high LDLc, high HDLc, and low TG. (See mdpi.com/2218-1989/12/5…)
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.
🙏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.
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.
@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.
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... 🧵
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... 🧵
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👇
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.
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.
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?
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)
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.
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
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
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...
Hence the enormous importance of studying those with extremely high LDL/ApoB at a population level...
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..
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.
(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.
The population of #LMHRs have extremely high levels of ApoB. But this pattern is a mix of very *low* TRL and very high TPL.
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
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.
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.
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. 🧵 ...
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.
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.
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...
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...
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...
With respect, the patient didn't immediately refuse any form of treatment...
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...
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)
Hence my interest in direct study on health conscious populations consuming high SFA (like many #LMHRs)
📊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 (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...
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?
When did you first hear of the Lean Mass Hyper-responder profile?
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…
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...
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...
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...
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...
Worth repeating that mine is a hypothesis and should be treated as such, hence the "cautious" part of the phrase...
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...
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...
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
Diets are often:
1) Low to no fruits & veg
2) Low to no grains
3) High animal protein
4) Low in plant oils
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…
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.
- 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
- Yes, lipoproteins + LPL = hydrolysis of TG to cells
