Zero cardiovascular risk

[mccoy]

I concur that, watching the data published in those articles and even allowing for some confounding factors at the lower end of ApoB concentration, there would not seem to be much benefit in ultra-low ApoB.

I would investigate further the procedures used in the articles, whether the ApoB risk parameter used for example was actually the area under the curve relative to some time horizon of what length.

The fact that some luminaries like Alan Sniderman insist on the zero-risk concept, the fact that neonatal ApoB is extremely low, the fact that those born with genetically-inhibited PCSK-9 exhibit no cardiovascular events, are very strong factors in favour of the zero-risk narrative.

Also, to keep ApoB really low without the use of very expensive PCSK-9 inhibitors, some attention to the diet is in order I believe.

[Mike Lustgarten]

Thanks Ron. Reverse causation could definitely be involved > 60y, but alternatively, cholesterol can have an immune-assisting function-when considering that immune function declines during aging, it suggests that while lower may be better at younger ages for ApoB and CVD risk, keeping it a little higher may be able to cover other adverse-health-related outcomes, too. 

[mccoy]

8 hours ago, Mike Lustgarten said:

but alternatively, cholesterol can have an immune-assisting function-when considering that immune function declines during aging, it suggests that while lower may be better at younger ages for ApoB and CVD risk, keeping it a little higher may be able to cover other adverse-health-related outcomes, too. 

Interesting hypothesis, what I would do is to collect a little more scientific evidence (publications) and submit them to Dr. Dayspring, asking him what is thought is on the subject, apparently he's available on twitter for any enquiries about lipidology and even personal questions on lipid panels.

I'm still sitting on the fence, that is I'm not taking any products to lower cholesterol.

[mccoy]

This I think is the seminal paper in 'Circulation' by Sniderman and co-authors which examines the advantages of ApoB lowering across a 30-years time horizon. It is worth reading the details, apparently the lowering scheme is not always very advantageous, they used non-HDL cholesterol in NHANES subjects as a metric.

 

The Expected 30-Year Benefits of Early Versus Delayed Primary Prevention of Cardiovascular Disease by Lipid Lowering

[mccoy]

The article is absolutely worth reading, one of the main points is that the benefits are greater to those who have greater non-HDL cholesterol, although they are perhaps nontrivial for the low-cholesterol group as well.

 

[mccoy]

One aspect to underline is that the article really does not separate low from ultra-low cholesterol, since there is only one group with Non-HDL<130 mg/dL, a class many people here probably belong to. 

[Mikii]

On 4/24/2023 at 6:45 AM, Ron Put said:

Statins in healthy people may not be a solution, as they tinker with the body's ability to make cholesterol, and we all need that 🙂 There are questions about diminishing brain functionality, as well as potential insulin resistance and other issues, which for healthy people may not be worth the risks.

Haven’t seen anyone mention yet the difference between the hydrophilic and lipophilic statins - the hydrophilic ones (rosuva, prava, fluva) have more selectivity for the liver and do not easily enter peripheral cells. They also do not cross the blood brain barrier (since dementia is linked to high cholesterol this may actually be a detriment, but if your priority is avoiding any potential statin side effects on the brain it’s the low risk choice). Doctors I have seen discuss this seem to mainly prescribe rosuvastatin (Crestor), then try pravastatin if someone has side effects from Crestor. 
 

Hydrophilic or Lipophilic Statins?

[mccoy]

22 hours ago, Mikii said:

Haven’t seen anyone mention yet the difference between the hydrophilic and lipophilic statins - the hydrophilic ones (rosuva, prava, fluva) have more selectivity for the liver and do not easily enter peripheral cells. They also do not cross the blood brain barrier (since dementia is linked to high cholesterol this may actually be a detriment, but if your priority is avoiding any potential statin side effects on the brain it’s the low risk choice). Doctors I have seen discuss this seem to mainly prescribe rosuvastatin (Crestor), then try pravastatin if someone has side effects from Crestor. 

Good catch, my wife's GP prescribed to her 5 mg/d of crestor, saying that this would have caused most probably no adverse effects and this is the same thing told by Tom Dayspring, 5 mg Crestor is also referred to as the 'baby statin'.

In the posted article they say the local effect on liver of the water-soluble statins could cause adverse effects in this organ (hypothetically)  but this is true (non hypothetically and rarely) as well of bempedoic acid, which is used to avoid the side effects of statins and targets specifically the liver.

[IgorF]

For the sake of completeness, an article from 2009, still cited in 2022:

 Nonpharmacologic treatment of dyslipidemia
Mark C Houston  1 , Sergio Fazio, Floyd H Chilton, Dan E Wise, Kathryn B Jones, Thomas A Barringer, Dean A Bramlet
Affiliations

    PMID: 19732602 DOI: 10.1016/j.pcad.2009.02.002

could be grabbed e.g. from https://www.hypertensioninstitute.com/pdf/Dyslipidemia Paper PCVD September 2009.pdf

 

A longread that is full of supplements assessments that are not so optimistic in 2023 perhaps. But that was "a janre" of zeroes, thus no questions why they had to do assessments.

Authors conclude:

Quote

The foundation for the treatment of dyslipidemia is
optimal nutrition, diet, and ideal body weight combined
with an aerobic and resistance exercise program in all
patients. Depending on degree of CV risk, nutritional
supplements or drug therapy is the next step. For the low-
to moderate-risk patient, nutritional supplements are the
second cornerstone of therapy. In the high- and very high-
risk patients, pharmacologic agents are needed and should
be used in conjunction with diet, nutrition, exercise,
weight loss, and scientifically proven nutritional supple-
ments. Clinical studies support the ability to reduce serum
cholesterol, LDL, and TGs by 30% to 40% with the
combination of diet, lifestyle modifications, and nutri-
tional supplements in most patients.

Generally speaking perhaps those who will be able to really(!) change their diet and lifestyle to close to mild CR (and cut out completely all UPF) seems do have reasonable chances to drop from TC around 200 to 140 but I personally would say that to get into 14x a person should have stature closer to 170cm/60kg than to common for caucasians with higher median frames (descendants of earlier industrialized countries) for which a reasonable target perhaps will look like 15x.

But if AUC is taken into account and a person spent a few decades @TC close to 200 then such a drop is probably not enough to decrease the risk thinking in the model terms used for calculations and individual cases could have different ways to go. I personally think rare body scans and more often ongoing ultrasonic examinations is the tool of choice for monitoring but who knows, maybe in a decade there will be more aggressive recomendations compiled by the organizations working on them.

 

Br,

Igor

 

 

Edited July 4, 2023 by IgorF

[mccoy]

With regards to supplements: a specific supplement, red rice yeast, has been proven to decrease cholesterol, but it contains a molecule, monacolin-K, which is actually a statin itself (lovastatin).

[IgorF]

Hm, interesting,

here https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697909/

authors report some significant results for some supplements, on the other hand here

https://www.nccih.nih.gov/health/red-yeast-rice

trace amounts if any are mentioned for the most supps, also with artificially added monacolin-K in some of them. It could be that other substances in the supps could create problems at the dosages enough to have 30-40 points of TC cutoff (if it at all possible that way).

In any case, thanks for pointing out, I missed this thing somehow.

 

[Ron Put]

Here is a good summary of LDL-C studies:
 

 

[Todd Allen]

I think this discussion on Plant Chompers is a good introduction to what is known and what we might learn from those who like myself develop "dangerously" high cholesterol when getting lean with carbohydrate restriction:  

 

[mccoy]

Thanks, Saved for listening. Some comments on this phenomenon have been made on most recent the stemtalk episode with Dom D'Agostino. As it turns out, LM hyper responders are quite a few. In the second part of the podcast, both Dom and Ken say they exhibit this effect. Dom D'agostino says it is correlated to very low carbs, since it's usually enough to eat 100 gr of carbs and it mysteriously disappears. Ken retorts: 'there is no free lunch', in the sense that you must accept the negative consequences of a keto diet together with the positive consequences.

Hint: they regard this LDL increase as actually or potentially detrimental

2nd hint: I regard Dominic D'Agostino as the most well-balanced and researched exponent of the keto world. No biases, no religious zeal, just facts and evidence, good and bad (in a podcast with Rhonda he downright says a few people have died as a consequence of a keto diet undertaken without adequate preparation).

Pls note: I'll comment further after having listened to the podcast posted by Todd

 

Edited August 18, 2023 by mccoy

[mccoy]

I listened to most of the Nick Notwitz podcast on LMHRs. It turns out that Norwitz is a Harvard postdoc who is himself a LMHR. He chose a keto diet to alleviate serious intestinal disorders. A very interesting detail is that he experimented a vegan keto diet with zero cholesterol and only 10% saturated fats, with no avail, his LDL only went down from 500 to about 400 mg/dL.

This means that a strategy like that envisaged by PEter Attia, eating mostly monounsaturated fats in a keto diet may not work in some individuals.

The current study on LMHRs is only going to last one year. I join the critics on the short time, according to the narrative from Schneider and others, the time horizon for atherosclerosis to fully develop is 30 years, far longer than the duration of the LMHR study.

OK, some of'em had been following a keto diet for 4 years, but the time is still too short to be conclusive. Probably, the subjects should be followed at 5 years intervals and check the development of coronary plaques, including soft plaques.

What the study is preliminary showing, though, is that there is not an inordinately accelerated formation of plaques from such hyper-high levels of LDL, showing that maybe it's a different ballgame with respect to familial hypercholesterolemia.

This subject is a very niche subject, dealing only with those who follow a strict keto diet, have a lean mass and exhibit ultra-high values of cholesterol and LDLc-ApoB

[Todd Allen]

7 hours ago, mccoy said:

This subject is a very niche subject, dealing only with those who follow a strict keto diet, have a lean mass and exhibit ultra-high values of cholesterol and LDLc-ApoB

I find it interesting though that among those who are strict keto and very lean this is not niche at all.  It looks like most perhaps nearly everyone could develop extremely high cholesterol although the needed levels of carbohydrate restriction, leanness and exercise vary.  My guess is eventually other measures with tighter correlation than total body fat will be identified such as liver fat, subcutaneous adipocyte size or perhaps something to do with liver glycogen depletion or how it is repleted.

Somewhat curious and possibly disturbing for me is that on my most recent labs I've had my first significantly discordant LDL value which crashed by over 100 points down to 220 despite continuing to get leaner, more active, more carb restricted with my highest ever intake of saturated fat and cholesterol and lowest amount of PUFA and calories coming from plants.  My other labs continued improving including all indicators of muscle health and reversal of SBMA but yet my LDL is tanking.

[Guest]

A cautionary tale of bempedoic acid - an LDL drug for those that can't take these horrible, horrible (did I mention horrible?) statins:

https://sensiblemed.substack.com/p/lipid-lowering-a-bempedoic-acid-subset

 

It is always important to ask, if all-cause mortality is moving in the correct direction. A drug that lowers CVD and CVD mortality - but does not affect all-cause mortality - is very suspect. It's a sign of some serious side effects going on.

Statins - despite being horrible, horrible drugs - have data backing up lower all-cause mortality for the at-risk patients assigned to them in the clinical studies. BA instead appears to be in the same camp as ezetimibe; both lowering LDL and CVD incidence - but having no benefit for mortality and lifespan for people at risk for CVD.

[mccoy]

Thanks for the warning. BA has been touted to be just about harmless, whereas some words of caution have been expressed for ezetimibe.

[Ron Put]

Interesting study:

Paradoxical Association Between Baseline Apolipoprotein B and Prognosis in Coronary Artery Disease: A 36,460 Chinese Cohort Study

There is no evidence, to my knowledge, that drug cocktails such as those Attia is pushing would help healthy subjects, and it is likely that they would be detrimental. Attia's claims that super low Apo B is the key to zero risk have no basis, other than his conjecture that because Apo B is super low in babies, it would be great for adults.

[Guest]

I would agree in so far, as he is advocating some drugs - in particular ezetimibe - that simply do not have data supporting lower all-cause mortality or just CVD-mortality.... ....despite lowering LDL. LDL is a surrogate marker for a drug, it's not a replacement delivering actual data on survival.

I find it actually a little frustrating, that Attia and Dayspring rightfully discuss studies on Niacin and fish oil at length, pointing out a lack of mortality benefit. And at the same time talking about ezetimibe without doing the same and just recommend it to their listeners. To be clear: there is no study among the dozen or so on ezetimibe, that shows lower all cause mortality or just CVD mortality.

The Chinese study you just cited is of course a cohort study, not an RCT. As there are a ton of factors that influence LDL/ApoB (including taking a statin BECAUSE of a previous CVD event), these are difficult to interpret.

Edited August 31, 2023 by Guest

[IgorF]

Attia in some discussion mentioned that in the past he suddenly discovered own non-zeroed calcium score and it was an unpleasant surprise for him. Thus personal bias even not taking into account all other possible things has its place.

He attributed it to heavy exercising regimens he was doing many years, if these things are correct then this is also a controversial way to explain and promote the lifestyle he does so far (and continuing to do with even more weak recent arguments like lactic acid benefits for the brain and so on).

We are all biased, especially with time when we are forgetting the least pleasant in favor of less disturbing things, our brains are just saving us(themselve) from suffering

Br,

Igor

Edited August 31, 2023 by IgorF

[mccoy]

10 hours ago, IgorF said:

Attia in some discussion mentioned that in the past he suddenly discovered own non-zeroed calcium score and it was an unpleasant surprise for him. Thus personal bias even not taking into account all other possible things has its place.

He also mentions a heavy genetic predisposition to myocardial infarction by familiarity, so he goes out on a limb to try and protect himself.  That's understandable and yes, it may constitute some sort of a bias.

On the other side, he may be preaching on the basis of the precautionary principle, let's get rid of the first horseman of death without any qualms, is his narrative and I cannot find that unreasonable.

Whoever had family members or friends victims of a heart attack or a stroke knows how tragic it can be, one moment they are (apparently) all right, the other they are dead or in a coma.

[Ron Put]

20 hours ago, mccoy said:

He also mentions a heavy genetic predisposition to myocardial infarction by familiarity, so he goes out on a limb to try and protect himself.  That's understandable and yes, it may constitute some sort of a bias.

Attie does not go out on a limb at all, since he actively pushes diets known to most likely increase cardiovascular disease risk.

Part of my reaction stems from initially being fooled by Attia and his "honest doctor in search of honest answers" routine. Attia (together with Garry Taubes) was bankrolled by the Veronica Atkins Foundation, and then by the Arnold Foundation, to the tune of $40+ million (Attia even did a special Drive podcast to tell the world that the Arnolds are the best philanthropists, ever).

The Arnolds, together with the meat and dairy industry, figured out that they could secure the meat and dairy industry's fortunes by attacking "Big Sugar" through funding research favorable to meat and dairy, and through mouthpieces like Attia, Nina Teicholtz and Gary Taubes. See this, for example:

https://www.politico.com/story/2015/10/the-money-behind-the-fight-over-healthy-eating-214517

Attia has been by far the sleekest of them all, and I actually admire his genius as a promoter. But he is a propagandist, and it took me about a year of listening to The Drive before I realized how manipulative his message is.

Having said that, I still listen to his show occasionally, because I can still learn some from it, despite the propaganda. Subject to verification, of course 🙂


 

[Ron Put]

 

20 hours ago, mccoy said:

On the other side, he may be preaching on the basis of the precautionary principle, let's get rid of the first horseman of death without any qualms, is his narrative and I cannot find that unreasonable.

It's true that Attia has personally moved away from Atkins/keto somewhat, and now tells different stories about the reasons (which is telling), but still supports the basic premise.

Instead of fat, he now promotes a high animal protein/high exercise regimen, which is still in line with his backers' goals, but is also at best unproven for longevity, and is more likely detrimental.

Attia attempts to offset the expected detrimental effects of a diet high in animal protein ("quality protein" as he terms it) by promoting his pharma cocktail, for which there is increasingly dubious evidence and which may in fact be harmful to healthy people in the long term.

Those with a genetic predisposition to very, very low Apo B and impaired fat absorption not only have numerous health issues, but there is no evidence that it leads to the avoidance of the "first horseman." See this, for example:

The cardiac lesions in Bassen-Kornzweig syndrome: Report of a case, with autopsy findings

I have to disagree with the claim that diet changes cannot be effective in healthy people, as a whole-food vegan diet appears to lower cholesterol by 20-30 percent, which is comparable to statins.

Attia (and Dayspring) keep making the preposterous claim that dietary cholesterol doesn't matter, while also acknowledging that about 20% of it gets in fact absorbed in healthy normal subjects, but never addressing the obvious contradiction. Again, 20% is the drop that many experience when they start statins.

There is plenty of evidence for the effect of diet, from non-industry-funded studies:

Vegetarian or vegan diets and blood lipids: a meta-analysis of randomized trials

and

Associations of Dietary Cholesterol or Egg Consumption With Incident Cardiovascular Disease and Mortality
 

[mccoy]

On 9/2/2023 at 3:21 AM, Ron Put said:

Those with a genetic predisposition to very, very low Apo B and impaired fat absorption not only have numerous health issues, but there is no evidence that it leads to the avoidance of the "first horseman." See this, for example:

The cardiac lesions in Bassen-Kornzweig syndrome: Report of a case, with autopsy findings

Ron, the above is a single case study, a study pretty low in the ladder of evidence. Besides, they seem to relate the death of the boy to malabsorption problems, strong anemia and extreme avitaminosis (fat-soluble vitamins not being absorbed).