Monday, June 24, 2019

On belief structures in lipidology

Dr Thomas "Just-take-the-statin" Dayspring writes on twitter:

"Any apoB-lipoprotein less than 70 nm in diameter can pass be pass thru endothelium - The LDLs are 20.5-25 nm. Remnants and IDLs are less than 70 nm and greater than 30 nm. The term small, dense LDL is way too simplistic - Big LDLs, like small LDs (less than 20.5 nm) if present in excess can invade artery"

This statement makes a prediction. It predicts that the accumulation of lipid in arteriosclerosis will be, initially, sub-endothelial.

As in this review of transcytosis (because passive "leakage" of LDLc down a concentration gradient across an endothelial cell layer is laughably impossible for particles over 6 nm across. No, that 6 nm is not a typo, according to the review). Not that "impossible" means anything to a lipidologist.

"During the initial stages of atherosclerosis, LDL particles are transported [transcytosed] across the EC [endothelial cell] barrier and accumulate in the subendothelial space".

So. All we need to do is a few post mortem examinations, find some poor people who had early arteriosclerosis at the time they died, and look for that lipid which will be sitting neatly under that single layer of endothelial cells lining their arteries. That is the prediction embedded in Dayspring's tweet.

If we go to this paper:

Early Human AtherosclerosisAccumulation of Lipid and Proteoglycans in Intimal Thickenings Followed by Macrophage Infiltration

EDIT: from a link in Subbotin's excellent "Excessive intimal hyperplasia in human coronary arteries before intimal lipid depositions is the initiation of coronary atherosclerosis and constitutes a therapeutic target" END EDIT

we can find real images of real arteries from real people who died of non related causes while carrying different levels of arteriosclerosis:























Left side images are van Giesen stained for histology, central images are with Sudan IV for lipid and right hand are immunostained with anti-CD68 antibodies to show macrophages. The pairs of small black arrowheads indicate the level where the intima stops and the outer media layer begins. The vascular endothelium is a single cell layer at the top of each image.

Let's look at the circled image in detail. This is an example of early atherosclerosis from a real human with real early changes who died of non related causes. It's just the sort of place you might hope to catch an LDLc particle creeping between the cells of a single endothelial layer or freshly spat out after transcytosis by an endothelial cell. Lipid stains bright red:


















Well, there's the lipid, deep, deep down at the junction of the intima and the media, right between the arrow heads...

There is none anywhere near the endothelial cell layer. If you believe that LDLc, as a result of a concentration gradient between artery and sub endothelial layers, "moves" or "invades" across that endothelial cell layer you have to explain how there is none at all in the sub-endothelial area and there is a progressive accumulation at the intima-muscularis junction. How does the lipid get from the top of the image to the deep spaces without any of it showing up in the lipid-free zone between the two?

"Beam me down, Scotty" is undoubtedly the most plausible explanation.

It is very, very hard to explain how utterly disreputable the lipid hypothesis is. All of this angst about increased LDLc and/or apoB counts on LC diets is based on the assumption that somewhere, somehow, cholesterol is the cause of heart disease. How LDLc "invades" (by active and controlled transcytosis!) the sub-endothelial space, disappears from there and then suddenly appears at over 200micrometres deeper, with none showing in the intervening zone requires a belief tenet which bears no resemblance to reality...

This was bollocks in the 1950s. My question is, as always, at what time did it stop being bollocks?

No one would reasonably doubt that the lipid deep down at the intima/media junction level comes from lipoproteins (though there are other plausible explanations). No one would doubt that loading the lipoproteins with with linoleic acid is likely to be a Bad Thing. No one would doubt that generating oxidative derivatives of the lipids in those lipoproteins might be a Bad Thing.

But trans-endothelial "invasion" is beyond belief.

This would suggest that all lipidologists are talking crap.

Nothing new there then.

Peter

51 comments:

ctviggen said...

After reading Ivor Cummin's recommendations to get a Coronary Arterial Calcification (CAC) scan done, I got one. It cost $99 in the US. I have "high" LDL-P (most times), quite "high" Lp(a) (about three times the "high" level and about 5 times the "optimal" level, all the time), high ApoB at times, etc. I have been on low carb/keto since 1/1/14, turn 55 this year. My CAC was zero. If these things, including that deadly saturated fat and eggs, are killing me, they at least aren't doing it through calcification of the arteries.

Also, because my cardiologist wants a blood test done, I did Dave Feldman's 6.5 day protocol (3 days low calorie, low fat -- I fasted 4.5 days -- followed by high animal fat, high calorie for 3 days). I radically changed my TC, LDL, LDL-p, HDL, Trigs, ApoB, everything but Lp(a) (went lower but not shockingly so) in three days. For instance, LDL went from 127 mg/dL to 106 mg/dL, trigs 135 to 68, LDL-p from 1170 to 1006, ApoB 116 to 83, etc., all in three days. His protocol made the numbers I'm reporting to my doctor (all other numbers I paid for myself and only go to me) look great, except LDL is slightly above 100, the current limit (they've lowered LDL so low that no one can really get that number).

I want to believe medical professionals, but they keep making idiotic statements like the one you discuss. And, to top it off, I needed a doctors prescription to get a CAC scan, and my cardiologist wouldn't give me the prescription (and insurance doesn't cover this anyway, so it would be paid out of my own pocket). I had to find a place that did not require a prescription and drive quite a while to get there. It makes me wonder about doctors.

Unknown said...

Well lipidologists HATE the CAC. Pharma HATE the CAC. Krazy interventional cardiologist HATE the CAC. Even Big Food hate the CAC. Guess why?

cavenewt said...
This comment has been removed by the author.
Hap said...

You are talking, of course, about the Subottin theory which disputes the dogma of trans endothelial lipid invasion....with pictures as above. I have asked my colleagues...who are some of the biggest names in cardiology, to comment ...even privately on this issue. I never get them to respond.

https://www.ncbi.nlm.nih.gov/pubmed/27265770

Bob Johnston said...

The Lipid Hypothesis also doesn't explain why veins are unaffected by LDL levels.

js290 said...

Observation (cholesterol) vs Concept (lipid hypothesis)... off base concepts... make mgmt decisions in wrong direction http://bit.ly/1lM3PFS

Peter said...

Thanks cave, updated.

Bob, the lipoid hypothesis explains essentially nothing. Started as garbage, no change since then...

js290, lots of wrong decisions. Interestingly there is no need for a therapy to be effective for it to be textbook.

Hap, yes, I mentioned Subbotin in an early draft of the post, his paper was where I got the link to the original images. The originals have better colour resolution than his versions. The post was was too cluttered and I've posted about his ideas some time ago, so it got edited out. He's clearly correct about large swathes of observation. I think he lacks insulin's action on IGF-1 receptors in the arterial wall designed to respond to platelet derived IGF-1... This is where pathological thickening seems to come from.

ctv, cool.

Unknown, well yes...

Peter

Peter said...

That will be lipid not lipoid!

bill said...

Thank you, thank you, thank you for posting this.
I can't stand how even in the low carb keto
community, people believe the lipid hypothesis.
As said above, you ask such advocates to comment on
this information and you get crickets.

Peter said...

bill, it's a war out there and repetitively refuting the lipid hypothesis is important. What disturbs me is that people who are making useful discoveries about plasma lipoproteins are tacitly accepting the sort of stupidity which says lipids creep across and/or between endothelial cells to give arteriosclerosis. Because there are lots of lipoprotein particles about........

Peter

Hap said...

I wanted to add that , if remembered correctly , Subbotin depends substantially on those histopathologic studies that he did not do. I believe it was a Japanese pathologist but don't remember the name...but it should be credited in the article. It was very good, convincing work.

Puddleg said...

If the cholesterol gradient can force endothelial cells to take in LDL particles then secrete them out the other side (why the other side?) then it should be able to perform a much easier function - forcing hepatocytes to take LDL particles up as they are designed to.
HDL particles are small enough to transcytose as part of their regular work. They carry a shitload of cholesterol in and around the sensitive parts. No-one thinks it gets stuck there.
It seems more plausible to me that lipid deposition is "intentional", in the existential sense - it is taken up because someone is looking for it, not because it just happens to be there. And/or, it is created in situ, as part of the over-driven growth process that seems to be a sine qua non for chronic cardiometabolic disease.

Hap said...

Puddleg
Agree and the cholesterol gradient explanation is without merit. But as we've seen the lipid hypothesis adherents will twist themselves inside out to prove their case. I've always been skeptical of the case glycocalyx afficianados make as well. there is a lot of lipid access and lipid trafficking through the VV. Stuff gets oxidized , insulin drives inflammation, macrophages show up from bone marraow...activated, cascade of asvd process.

there is also the weird case that fatty streaks are also seen in newborns. I've seen articles that say this is the seed of future asvd lesions. (sorry I don't have time to fish it out of my files) I don't find this compelling on any level. Some say it is related to intrauterine sex hormone activity...and that disappear with time. Otherwise, all prenatal care should include a Statin pill to get that LDL down ...right!?

Peter said...

Hap, the chap was Nakashima. He's the communicating author of the linked paper the images are taken from. The Japan appears to be a nation which has produced some significant cholesterol skepticism over the years

Peter

Unknown said...

Hi Peter,

I love your posts and I am waiting impatiently for the next ones.

I am confused about this one. The original tweet does not say much, and I do not see any prediction there. He’s just being vague. He does not define “invade artery” and does not say what happens to the LDL once it passed through the EC.

He as do you agree on the accumulation of lipid in the subendothelial area. This can be defined as directly beneath the EC or deep down next to the muscle cells. He does not say. No mechanism is proposed. He’s just being vague, and a lot of ppl might think he’s makes an intelligent argument.

The accumulation in the pics show lipids but are not specifically stained for ApoB. So, who knows that these are? HDL stuck in traffic?

The impairment of the EC glycocalyx does increase LDL traffic. Insulin does stimulate ALK1 and LDLR (and SB-R1? Thus increasing HDL traffic as well? ). Hyperglycaemia does change the proteoglycans of the intima and SMC can be insulin resistant. Hyperglycaemia does make SMC proliferate.
I agree that more LDL in plasma does not necessarily translate into more transcytosis or accumulation for that matter. Or maybe it does if the EC-barrier is impaired and the SMC screwed?

Fasting increases LDL (as published and from my own experience) and decreases insulin at the same time. (Of course it does since insulin regulates ApoB-secretion and LDLR.) But does fasting increase risk of atherosclerosis? Is the lipoprotein flux in the arterial walls increased or decreased during water-fasting? How does fat get to the SMC assuming a ketogenic diet or water fasting? Afterall it’s just muscle, it eats fatty acids if it can.

It seems to me that the flux is a key process here. (Any high-resolution 3D videos on this published yet?) It’s probably rubbish on a high-fat-high-glycaemic diet as fat must travel but sugar blocks the pathways.

raphi said...

nice one Peter

and welcome to "peanut gallery", as Peter Attia has proclaimed from a top his high horse. you should really be talking with "the experts", dontcha know? at least that's how he admonished Dave Feldman...

Hap said...

Yes, Raphi...gallery of deplorable skeptics. However, I often have pangs of concern that my skepticism is on overdrive. But I don't fall for the "expert" fallacy. I just want the anointed experts to respond reasonably to criticism.

i've asked PA to consider a podcast on industrial seed oils in the food supply and their effects on health. Was hoping that he would have Tucker on...as who would have a better grasp of the totality of evidence? I've never received a response but as tucker has opined "never gonna happen".

Peter said...

Hi Unknown,

Lots of points. To me (and Zhang et al in the transcytosis review) the definition of subendothelial is immediately below the endothelial cell layer. You could define subendothelial as including the whole of the intima (and go on to include the muscularis and adventitia for that matter), but you still have to explain how an LDL particle gets from the site of exocytosis to the intima/muscularis junction.

Figure 1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167422/figure/F1/ shows how modern lipidologists think the process occurs at the one cell layer and where they consider the subendothelial space to be located.

No ApoBs. Yep. So either ApoBs are not involved in the initial lipid build up (a fascinating thought!), or they are and they get deep from the subendothelial space without being visible on histology during the transition process. Histology is, as you intimate, a static image. But the argument is that a concentration gradient of LDLc particles drives the process so I’m not sure I can accept the “travel without being seen, then stop” concept.

I feel the changes in LDLc that occur in fasting/ketogenic eating are extremely interesting and crucial to the ultimate destruction of the lipid hypothesis but, obviously, irrelevant to determining how arteriosclerosis starts and progresses. That’s good enough for me so it’s excellent work, even if tainted with the disreputable lipid hypothesis.

Have you read Subbotin’s hypothesis (there’s a link edited in to the paper now)? He identifies pathological thickening of the intima as the core change. He has no suggestion re the cause of this but it’s something I was interested in back in 2010. My personal idea is that this thickening is either benign if localised to high stress areas where platelet derived IGF-1 reinforces normal the intima. It’s pathological if chronic hyperinsulinaemia interacts with IGF-1 receptors to produce an intima too thick for diffusion of oxygen and nutrients to reach all areas. This area vascularises and blood vessels deliver LDLc as part of the innate immune response to the intimal tissues which are usually avascular. If the LDLc is full of linoleic acid oxidation products, bring on the chemocractants for macrophages.

Back to Dr Statinator: “He’s just being vague, and a lot of ppl might think he’s makes an intelligent argument”. Literally millions of people think his tweet might represent an intelligent argument. They are mistaken, unfortunately.

I’ve looked hard for whether insulinomas drive arteriosclerosis but they are sufficiently rare that the question isn’t usually asked. Acromegaly however, with markedly elevated IGF-1, drives arteriosclerosis like a lipidologist writing a statin prescription.

Peter

Oh, as a brief aside, Fig 1 as above shows that LDLc is translocated using the LDLr (as well as ALK1, SR-B1 and caveolin at least) to get through the cell to the sub endothelial space. The prediction from this is that LDLr deficiency, as in FH, should protect against transcytosis of LDLc! Had me laughing out loud. Of course this LDLc [particular type of transcytosis only occurs at the blood brain barrier rather than in coronary arteries (so the review suggests). Still good for a giggle.

Peter said...

raphi, Peter Attia appears to be utterly lost in the Lipid Hypothesis, there is no hope for him. Poor chap. I'd say bring on the peanuts but I'm not that sort of LC!

Peter

Marc Rouleau said...

Seems like the latest effort to shine a light on neovascularization of the intima from the medial side as the initiating pathology is bearing fruit. The consensus apologists are beginning to advance tortured explanations like this one: https://twitter.com/POhukainen/status/1143624767142080518.

Edward Edmonds said...

Your posts featuring histology are like click bait for me ... It became bollocks when we stopped looking at physical evidence ;) And of course, now we have the imprecision of IHC to further the madness, I specifically warned of this years ago in a post and I wasn't the only one (van der Loos published on this), this isn't Hillman talk, this is a gross misunderstanding of physiology contrasted with the limits of detection methodology; and now we have this:

https://www.hopkinsmedicine.org/news/newsroom/news-releases/johns-hopkins-researchers-find-widely-inconsistent-use-of-antibodies-in-lab-experiments

This is just the tip of the iceberg, even with proper "validation" there is a lack of consistency. Histotechnology is a mystical field.

Best wishes,
Edward

Edward Edmonds said...

Path's read what they see, like sniffing dogs, most people don't understand there is an entire field dedicated to "detection" or "producing evidence", I can "manufacture" all sorts of "diseases" with IHC in normal tissue. LOL.

Peter said...

Edward, Mel is part of the immuno group at her work. Yes, interpretation is a nightmare in some cases. Negative and positive controls are included alongside every immuno run and read by a pathologist. Sadly that is not the case in every other commercial laboratory. Apparently positive controls do not invariably make a sound business plan! Ditto ZN staining of granulomatous inflammatory lesions, same lab. Well duh. And once you start with fudge factor in science I guess there is no end...

Marc, I feel honoured!

Peter

Geta said...

Hello Peter,

Indeed, I have read Subbotin’s review. I did not know the intima actually grows. I should have known since centenarians have the thickest ones (23912686), but I did not make the connection.

An impaired endothelial barrier in conjunction with neovascularization and unhealthy lipoproteins could make a start for AS. I say lipoproteins because high HDL isn’t sunshine weather either. What lipoprotein transports cholesterol the best? HDL comes from the blood into tissue and exits via lymph vessels. LDL does not like to travel much. HDL does. Does the neovascularization also include a healthy/normal neo-lymphangiogenesis? Is the drainage still intact?
(I speculate here because the lipid hypothesis does not make sense to me.)

Why the neovasc.?... Why do scars develop? (I agree.) How to decrease excessive growth? The same way we decrease insulin/IGF-1. And best done when young-ish still.

Why (and how) would LDLc bee needed for the immune response in the intima? Just wondering…bugs? tissue damage?

PS: I find it fascinating that VSMC do the Warburg dance for proliferation as well. (Cancer cells, yes. Immune cells, yes. Arterial muscle cells? Nice.)

Greetings Unknown

Peter said...

Uknown,

That will be media not muscularis in the above comment. Apologies.

Peter

Peter said...

Hi Geta,

Thanks for the link. As far as I can see many lipoproteins are core components of the innate immune system and local tissue damage needs to have a response and response in the face of continued injury is the essence of pathology...

Yes, the Warburg effect is normal when energy demands outstrip the supply from ox phos. Less efficient but faster.

Peter

Hap said...

Yes...and the lymph system integral to a vigorous immune response to damage in arteries. Chronicity results in dysfunction. Epicardial fat (a visceral fat) is inlamed (we see it at CT and PET FDG). Cholesterol efflux goes to hell. Gabor would summon the gut demons. He may be correct.

If the lipid hyenas would just have a little humility and address the issues instead of tripling down, that could be nice

cavenewt said...

If I may humbly ask after reading the Twitter thread cited by Marc, what about the criticism involving scale? For those of us who aren't knowledgeable enough to see the torturousness of that argument.

raphi said...

cavenewt,

The 'Twitter/scale argument' boils down to

"histology is difficult, and if you could zoom in you'd see a lot of nasty lipoprotein stuck in the net"

Now, this is laughable of course because it doesn't address the question of the gradient - if i can see it without a x800 and can already see it without the zoom, am i too expect to suddenly see a different pattern with an x800 zoom? This is classical special pleading and post-hoc reasoning - they make it unfalsifiable. A good way to spot bad scientists and/or corrupt individuals.

Oh, and apparently they "know" what you'd would see at an x800 zoom but we Cholesterol Denialists shouldn't see what's right in front of us.

Right

Hap said...

It is true the warburg effect favors the faster glycolysis. In cancer the xplanations not entirely satisfying. Some like that cancer cells need the energy to make proteins, so glycolysis. Seyfried has shown substrate phosphorylation bypassing oxidative phosphorylation occuring in mitochondria (who may have defective oxphos capacities)

Marc Rouleau said...

cavenewt, adding to Raphi's remarks, I think Pauli wants us to believe that LDL particles burrow in from the lumen and puddle up against the demarcation point between the outer intima and the inner media. They always concentrate there because, hmm, the wall is sticky. And only later in the disease process can we see sufficient concentrations of particles near their inner intima entry point to show up at the resolution used by Nakashima et al. Unfortunately, his reference purporting to prove the existence of the invisible particles is not pertinent - the guys with the cool electron microscope used it only to examine the plaques that appear in late stage disease.

Instead of believing in fantasy explanations for the inconvenient photos, we might take a closer look at Geiringer (cited by Subbotin - https://sci-hub.tw/10.1002/path.1700630204). After examining 300 aortas and 100 hearts, Geiringer offered these conclusions in 1951:

1. The normal arterial intima is an avascular structure.

2. It acquires a secondary blood supply if it grows beyond a certain critical thickness.

3. This critical thickness, which varies with each artery, is about 0·5 mm. in the aorta and 0·35 mm. in the proximal part of the anterior descending branch of the left coronary.

4. Intimal vascularisation occurs either through an extension of the adventitial plexus into and through the media or by retention of the vascular network of organising mural thrombi. When both processes occur in the same vessel, anastomoses usually form.

5. This adventitious blood supply of the intima is liable to interference, and most of the clinical effects of atherosclerosis can be traced to the resulting ischremic necrosis of the intima.

6. These phenomena can be appreciated and studied in uninjected routine sections.

Disorganized neovascularization of the outer intima is clearly visible in Geiringer's photos and is an obvious conduit for invasion of unwanted particles.

Bob said...

Marc,

Thank you for the references (both the Tweet and the Geiringer article). I was pleasantly surprised as a layman to find the Geiringer paper fairly easy to follow.

Be interesting to know what happened to this line of research. I assume it gave way to the cholesterol hypothesis of the late 1950's. There certainly seems to be no reason why Geiringer's methods couldn't be repeated today with the better tools now available.

The two approaches to CVD research couldn't be more different: Studying the process vs looking for dietary associations. Sadly, the "magic of food" approach won out.

And thanks also to Peter for occasionally bashing cholesterol. It seems to bring out the best from the dissenting camp for the enlightenment of folks like me.

cavenewt said...

Marc

Thank you so much for the clarification:

"And only later in the disease process can we see sufficient concentrations of particles near their inner intima entry point to show up at the resolution used by Nakashima et al. Unfortunately, his reference purporting to prove the existence of the invisible particles is not pertinent - the guys with the cool electron microscope used it only to examine the plaques that appear in late stage disease."

The tweet thread gives the distinct impression that with sufficient resolution one would be able to see individual lipid particles slouching their way toward the final resting pool.

Your further comments were very easily understood also. I appreciate it!

Puddleg said...

@ Geta
" high HDL isn’t sunshine weather either. "
Read this report to understand why very high HDL can indicate risk in one context and the absence of it in another.
https://scienceofhumanpotential.files.wordpress.com/2016/11/hdl-excess-cetp.pdf
"overproduction of ApoA1", which is what happens when you eat fat over carbs, is protective in their description, elevations in HDL due to inhibitions of factors involved in reverse cholesterol transport, such as CETP, are not.

Hap said...

Puddleg
that's a great point . We should understand what general mechanisms increase HDL due to inhibitions of the factors. Do you have insights there?

Hap said...

We know what generally inhibits CEC through HDL......Inflammation, intestinal barrier disruption, excessive VAT etc. but I don't that actually elevates HDL.

Hap said...

Listen to PA podcast with Jason Fung. I think it is pretty good. there is a discussion of hyperinsulinemia and dysregulated growth process. they walk right up to ASVD and then..poof...do NOT GET IT.

DIT a normal process but can be upregulated with certain inputs like HTN (hyperinsulinemia anyone? Ox stress and other processes. intimal thickening not spared and cascade of events follow.

altavista said...

Attia might be just an above-average ex-McKinsey shyster, and I owe a great debt of gratitude to Peter, but am sympathetic to the peanut gallery remark.
It's "easy" to sit back and poke holes at others' studies, wrong mice, wrong chow, wrong mitochondria, that proves nothing etc. but to be fair there isn't a study that proves eating a stick of butter/day like I do, or running the cholesterol 300% the limit, in vivo, has any benefits either. We just don't know. So the other side doesn't enjoy the same peanut benefits :)

Peter said...

alta, you could also add wrong paradigm....... Someone has to be wrong! But although we don't know what adding serious amounts of saturated fat to ones diet will really do, long term, the short term biomarkers (for what they're worth) look good. Especially assuming you reach old age and are hoping for a high cholesterol reading. But as you say, ultimately, we dunno.

Peter

Peter said...

Sorry alt, just deleted your comment in a mis-click during a spam clear out. Feel free to repost

Peter

karl said...

Much as Malcolm Kendrick has said and been attacked for - ( if you are in the medical business - it is dangerous to point out false dogma).

An even simpler bit - if the LDL nonsense had any validity - why don't any of the other 16 drugs that reduce LDL would have a positive effect? They just don't. Statins very small effect is probably due to a weak nitric oxide effect - or is an artifact of biased research.

The lack of effect of other cholesterol lowering drugs should end the routine testing.

Parroted ungrounded narratives of the medical business that promise false hopes is actually doing real harm.

Passthecream said...

Hi Peter, great post and some fantastic comments also.

I'm wondering if anyone can clarify something for me. Say you have a couple of fried eggs for breakfast, fried in that good 75% linoleic safflower oil on toast buttered with that good margariney stuff -> all gets munched up, macerated, intercalated, emulsified, lipased and much of it is assimilated, processed by enterocytes and stuck onto chylomicrons to be distributed. In addition to re-esterified linoleate t.a.g., is the cholesterol itself esterified with the dietary linoleate? So we have an efficient delivery system pushing various esters of linoleic acid all over the place?

If so, and the linoleates are as damaging as Spitteller found, this is the basis of an easily understood 'Inverse Lipid Hypothesis' eg when in doubt saturate it.


altavista said...

Guess what I was trying to say was his podcast with Ethan Weisz was worth it, esp. the last half where he admits they don't have a clue ("I'll tell you something else tomorrow")

Oh, and sents don't work either, after they stented tens of thousands? But he came up with a keto breathalyzer. Shocking for a lipidologist?

Hap said...

slightly confused Alt

Was this Ethan Weiss podcast or Ethan on another podcast...whom?

Hap

altavista said...

Yes, the Ethan Weiss podcast on peter attia, as someone referred to it above.

Hap said...

FWIW
https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.12616

Hap said...

https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.12616

FWIW

altavista said...

Love it! I bet it won't get any comments from the peanut gallery. lol

As expected, things are more complex than any one study can resolve. Lipids only ok, lipids+CRP+Apob not so much. But we kinda knew that.

I've come to the conclusion that I just hope Peter's vet biochemistry is in tip-top shape, until AI is unleashed on these studies to give a definitive answer. :)

https://www.vice.com/en_us/article/neagpb/ai-trained-on-old-scientific-papers-makes-discoveries-humans-missed

Bob said...

Hap,

There is also a podcast with Ethan Weiss on a forum called LowCarb MD.

http://lowcarbmd.com/episode-9-dr-ethan-weiss

Fred Lander said...

I made a long comment, too long for here, at a video by Dr. Paul Mason, and included long quotes from Vladimir Subbotin, Dr. Kraft, Yutaka Nakashima, and from a 2017 publication , " Modifications in Retinal Mitochondrial Respiration Precede Type 2 Diabetes and Protracted Microvascular Retinopathy "

Are other possible explanations for this diffuse intimal thickening being explored, besides some type of mitochondrial dysfunction? Can we do a brain storm session here to explore possibilities , with no judgment of merit?

Could there be a copper, zinc imbalance, outside the range of our evolutionary familiarity?
( got the idea on that one from Dr. Terry Wahls ).

What are some practical measures for people to take who are having problems making the big carbohydrate adjustments, and also have tight budgets? Are pomegranate seed oil, 12 drops twice a day, 1 tbsp walnut oil with meals, and aged garlic extract the best candidates? Should kiwi fruit be included, even with the fructose?

Peter said...

Certainly copper deficiency produces massive intimal thickening but I've not looked at the mechanism at all...

Peter