OUTLIVE-Peter Attia's book

[mccoy]

At last it is available, I preordered a hard copy whose delivery was postponed, so I downloaded a kindle copy. I was a little bit disappointed. The book is not the super-nerdy, hyper-specialist treatise I was hoping for, rather a tamed narrative meant for the general public. I canceled my order of the hard copy. Of course the book maintains its great interest and usefulness but it is not a technical manual to be readily consulted to design longevity and healthspan strategies. Not the engineering manual I believed. That was maybe the 1st version, rejected by the publisher(s).

Anyhow, the book is still extremely useful to know the current ideas and strategies of this formidable exponent of preventive medicine.  I recommend it, it's only about US$ 10 in the kindle format.

 

 

[mccoy]

Chapter 7 of the book: 'The ticker'.

The book starts being interesting. This chapter is an abstract of the plethora of material Peter Attia has illustrated in hours and hours of his podcast. I confess up to now I've been not a little confused, since such plentitude of info comes with the difficulty to extract the more practically useful info. Here, we find it at last, together with some very interesting facts. In essence, as already discussed in this forum, ApoB according to Attia is the main indicator of atheroscelrotic risk, a proven causative agent, together with lipoprotein(a). ApoB coats every LDL and VLDL particle, the types responsible of damage to the endothelial structure. Also, ApoB concentration is correlated to the number of LDL and VLDL particles. A higher number has a greater probability to initiate plaques because of the higher probability of damaging impacts with the endothelium. Lp(a) is generically imposed and is a pretty bad beast, impossible to keep at bay without specific drugs (PCSK) inhibitors). The details of the various stages of atherosclerosis are explained, adding the discomforting news that the signs of atherosclerosis have been observed in very young people. 

Then we have the practical chapter: 'How to reduce cardiovascular risk'.

Here, Peter proposed a rather drastic strategy: decrease the ApoB concentration to that of children (20-30 mg/dL), to nip in the bud any ahterosclerotic phenomena.

Such a strategy consist of:

1. Dietary intervention. Peter suggests eating monounsaturated fats prevalently. In his experience, about 33% to 50% of people who consume high amounts of saturated fats will experience a dramatic increase in ApoB particles.
2. Pharmaceutical intervention. This is done by increasing ApoB clearance mainly by increasing the activity LDL receptors in the liver. Other drugs like Ezetimibe lower inestinal absorption of cholesterol. Often 2 cholesterol-lowering drugs are used and there is a specific subchapter on such drugs.

He then describes the Sniderman article, based on a 30 years time horizon, which underlines the benefit of early cholesterol-lowering interventions.

The core concept of the proposed strategy is well summarized in the following sentence.

 

Edited April 22, 2023 by mccoy

[mccoy]

Cholesterol lowering strategy continuation.

Statins are the most used class of drugs. In 5% of the population they cause muscle soreness. Other side effects may be glucose intolerance and increase in liver enzymes (asymptomatic). Other drugs are effective but expensive. PCSK inhibitors are used to lower ApoB and Lp(a). Fibrates are use to lower triglycerides, which contribute to high ApoB. EPA is another drug use to lower cholesterol when trigs are high.

 

[Ron Put]

I watch a lot of Attia's shows, as I find them informative on many subjects. But he exhibits high levels of confirmation bias in selecting his guests `(most of whom are selling something, either directly or indirectly) and in the conclusions he reaches during his shows. 

I have to assume that Attia is sincere when he claims that what you eat has little or no bearing on one's health, or that he abandoned his keto diet not because of health concerns, but because dieting may somehow have psychological impact on his kids. Even if it makes no sense to me.

But what makes even less sense is that he claims that animal protein is of utmost importance to longevity, and mentions his daily regimen of a bucket of eggs and steak, and then tells us that the CVD impact is inconsequential, or at least nothing that another bucket of pharmaceuticals cannot fix.

I would listen to him if you want muscles, but would completely ignore him if you care about long-term health and longevity.

For what it's worth, I am significantly older than him and my APO B is lower than that of virtually all of his guests I have heard mention their results, and when I stick to relatively low fat meals mine goes in the low 60s. My BP is below 115/70 and my inflammation markers are barely measurable. All without any pharmaceuticals. At this point, I feel I am more qualified to write a book on longevity than Attia 😄 
 

[Ron Put]

I knew that Attia has various tie-ins and people sometimes shill on his show, but I just searched for tie-ins and this popped up (yep, the headline is over the top...). I haven't checked it yet, but if it checks out even partially, it would make sense of Attia's apparent confirmation bias I mentioned above:

Dr. Peter Attia: Hack, Liar and All Round Disgusting Individual

Apparently Peter and his buddy Gary Taubes just love themselves some crappy pseudoscience. Both of them are funded by the Arnold Foundation, with substantial ties to animal agriculture industry lobbying.  Marion Nestle notes the Arnold’s working relationship with a National Restaurant Association and the National Cattlemen’s Beef Association consultant.

[IgorF]

There is an interview with Attia somewhere on yt, I don't remember who interviewed him but it is about him as a person, not as somebody connected to his work and a frontman of his work. There are some aspects that could not be easily derived from his Drives, e.g. he was seriously obsessed to become a boxer in the early years, his sport-related traumas etc. He is obviously biased towards strenght-related sport areas, endurance behind reasonable limits (I know, reasonability here is not a "measurable" term but rather in "common wisdom" sense). I am almost sure he dropped keto due to sport performance reasons as the main factor (the same as why we don't see ~50%/~50%~ carbs/keto distribution of top performers) and he is biased to say it directly, but that is just my guessing.

Despite of this bias he really delivers a lot of things to think about, introducing people whose books I enjoyed reading and so on. So we have to just keep in mind that he is in an "intensive body usage" camp and the rules there are different from all "non-intensive" ones.

Br,

Igor

[Ron Put]

21 minutes ago, IgorF said:

I am almost sure he dropped keto due to sport performance reasons as the main factor...

Hi, Igor. I agree that there is enough useful information presented on many of his shows, which is why I listen to many of them 🙂 But there is also plenty of assertions that are presented as facts, when I know that they are not true.

In any case, I heard him say (almost certain) on the Drive within the last few months that he abandoned keto not because of health issues, but because his daughter is coming to an age where he is worried that his diet may screw her up, her being, you know, a susceptible girl. I remember thinking it did not ring genuine, which is why I probably remember it.

[IgorF]

Hi Ron,

I think the explanation is in dissonance theory - the more we invest in something the more we tend to justify this something and for the things to work at best we have to first convince ourselves. Attia invested a lot into his sport-related lifestyle of the early years and also into risky experiments etc. So he have to have answers on that. With time they will change but this does not guarantee they will have something close to "reality" as it is seen from the outside.

I think he believes somehow in his last answer, maybe because a "vantage point changed" (more interviews about maximizing life experience/goals in the last series).

I also see in my own lifeline the same transformations of justifications for the things I understand were mistakes, not 100% compatible with my ethics, and so on.

There are even more interesting cases that are very hard to answer if people do really believe in their justifications or a really champions in doing bad smelling business - Sackler's history described in the "Empire of Pain" or Wakefield's antivac trajectory - after reading the bestseller books on these stories I can't answer for sure they are not self-convinced in what they are doing.

Br,

Igor

[Saul]

I never watch and Attia videos; I have always doubted that there's anything in them worth watching.

  --   Saul

[mccoy]

7 hours ago, Ron Put said:

In any case, I heard him say (almost certain) on the Drive within the last few months that he abandoned keto not because of health issues, but because his daughter is coming to an age where he is worried that his diet may screw her up, her being, you know, a susceptible girl. I remember thinking it did not ring genuine, which is why I probably remember it.

That's one of the reasons he cites, but the main reason is that the keto diet ceased to be useful after he lost his visceral fat. After having been a supporter of the keto club, he became aware that this regimen cannot be sustained for long. He gave many reasons to why he quit, among which he couldn't eat copious amounts of vegetables without going out of ketosis, he couldn't eat his kids' leftovers, it is not a practical diet and so on. The influence on his girl is just one of the many reasons. The main one is simple: he wised up.

Re. protein: he follows DAn Layman's muscle-centrice theory, according to which muscles are the main longevity organs and sarcopenia must be avoided at all costs.

Re. exercise: he clearly states (and provides evidence) that exercise is the most important longevity drug. Pharmaceutical drugs come behind. I think he goes a little overboard with it when he enumerates the physical requirements he asks of his clients, but the power of exercise and highly structured exercise is undeniable.

Re. diet: he has evidently grown nauseated by the religion-like dietary affiliations. I myself have observed how medical people from both sides, keto, lowcarb, paleo, vegan, can stick to unreasonable ideas. At this point, the biochemical framework appears to be the only neutral region in the dietary mayhem. I think also that everyone of us has realized that some scientific articles are biased and have been set up to show determined conclusions, according to the preferences of the authors (be they keto or vegan or whatsoever other affiliation).

Re. drugs: yes, Peter Attia sometimes runs too fast. I wrote in the recent thread on zero cardiovascular risk that some of his suggestions cannot be followed in Italy (and probably in many other countries worldwide). PCSK9 inhibitors are simply out of reach of patients, except the seriously compromised ones who have been hospitalized, so cannot be used in preventive medicine for now. On the other side, not everyone is so lucky as Ron to have optimal metabolic parameters and this is a war where the enemy chiefs are the four horsemen of death. In a war against such portentous enemies, we should use all the weapons we have available, once their validity and relative safety has been proved.

Edited April 24, 2023 by mccoy

[mccoy]

18 hours ago, Ron Put said:

I have heard mention their results, and when I stick to relatively low fat meals mine goes in the low 60s.

According to Attia's rationale, your numbers are still high. Reaching levels of 20-30 mg/dL needs pharmaceutical interventions. The latter values are, according to Attia's procedure and suggested by specific literature (a Sniderman article is cited) the levels needed to disarm the first horseman of death.

I would like to remind that we already discussed the suggestions from Luigi Fontana. Even according to him, LDL cholesterol cannot be too low.

[mccoy]

So, I reiterate my question. How good would it be to tick off cardiovascular risk from our concerns. Would it grant the assumption of cholesterol lowering drugs.

That way we may have more time at disposals to fight the other horsemen of death and notably cancer which is probably the worst of all.

[Sibiriak]

2 hours ago, mccoy said:

Reaching levels of 20-30 mg/dL needs pharmaceutical interventions   [...].we already discussed the suggestions from Luigi Fontana. Even according to him, LDL cholesterol cannot be too low.

That's right.  But Fontana does say that heart attack risk "approaches zero at an LDL level of about 57 mg/dl. "

Quote

According to the 2018 guidelines of the American Heart Association, an optimal level is less than 100 mg/dl (2.6 mmol/L) for otherwise healthy people.14 However, accumulating evidence suggests that it should be much less, with the lower the better.15 Professors Goldstein and Brown, who won the 1985 Nobel prize for their studies on cholesterol biology, have postulated that we humans have been designed to maintain LDL-cholesterol levels in the range of 25 mg/dl.  [...]

Indeed, as illustrated in Figure 33, the results of many primary prevention trials with stains have shown that the probability of developing a heart attack is linearly related with blood cholesterol concentrations, and the risk approaches zero at an LDL level of about 57 mg/dl. 

[...]We should keep in mind that the cardiovascular benefits could be much larger if plasma cholesterol was kept lower throughout our entire life, thus preventing the development of the atherosclerotic plaques from the beginning. Indeed, individuals who were born with mutations that inactivate the PCSK9 gene (which provides orders for making a protein that helps regulate the amount of blood cholesterol) have plasma LDL-cholesterol levels that are approximately 30 per cent lower (levels similar to those induced by treatment with the cholesterol lowering drugs called statins), and experience a 90 per cent reduction in heart attacks, independently of smoking, hypertension and diabetes.23 In contrast, a similar 30 per cent reduction of serum LDL-cholesterol with statins results in only a 30 per cent lesser risk of coronary events.

These data suggest that lifelong lower levels of plasma LDL-cholesterol are much more effective than late LDL-cholesterol reductions induced by statins in preventing coronary heart disease.24 Moreover, they suggest that the extremely low incidence of coronary heart disease observed by Ancel Keys and others in South Italy, Crete, Japan and Okinawa in the 1950s was probably due, at least in part, to the lower levels of plasma LDL-cholesterol that these populations had experienced throughout life.   --Luigi Fontana, Path to Longevity (pp. 268-270)

 

Edited April 25, 2023 by Sibiriak

[IgorF]

A guess - Attia likes to use "area under the curve" as an illustration, thus from this model (from linearity of the function mentioned) would come 20-30. E.g. for those who was already exposed half-a-lifetime to levels higher than 60 the second half should be covered by lower levels for the area to have the same value. And since the second part of life is also more prone to decrease of housekeeping of already anchored particles - it would be better to be as "aggressive" as possible with this metric.

That is a possible ressemblence of the logic.

 

I personally am not sure if this is reliable. It should work if "dragon's teeth" already seeded are mostly linear in their chances to became a problem, but they are not. Maybe in larger and longer investigations we will see less linearity, who knows.

 

Br,

Igor

Edited April 25, 2023 by IgorF

[mccoy]

5 hours ago, Sibiriak said:

These data suggest that lifelong lower levels of plasma LDL-cholesterol are much more effective than late LDL-cholesterol reductions induced by statins in preventing coronary heart disease

What comes to my mind is something similar to the AUC concept hinted at by Igor. People who take statins late in life have usually, according to the present non-preventive protocols of medicine, have had quite high levels of cholesterol for several years, maybe decades. That brought about a plaque buildup which is not easily counteracted by late life cholesterol lowering interventions. That's why Attia insists on the 30-years horizon cited by lipidologists like Sniderman and Libby.

Also, arguably the adage 'better late than never' is valid in the case of atherosclerotic risk, and reducing drastically cholesterol levels even latish in life will block plaque accumulations and may cause some reabsorption of existing plaques.

Last, I wonder if Fontana's remarks are meant specifically for coronary heart disease whereas Attia's protocol is meant specifically for a wider array of cardiovascular and cerebrovascular hazards.

Edited April 25, 2023 by mccoy

[mccoy]

6 hours ago, Sibiriak said:

Indeed, as illustrated in Figure 33, the results of many primary prevention trials with stains have shown that the probability of developing a heart attack is linearly related with blood cholesterol concentrations, and the risk approaches zero at an LDL level of about 57 mg/dl. 

Thanks to Sibiriak for recalling the words from Fontana. His reference to figure 33 is probably related to the specific case of CHD rates, whereas in other parts he seems to suggest that the lower LDL, the better. In another table he provides a realistic optimal range of LDL of 50-70 mg/dL

 

[mccoy]

[mccoy]

The reference to figure 33 is now clear to me. That's specifically related to CHD events and moreover the zero-risk intercept is a construct of the minimum square line, which is an extrapolation and not precisely or necessarily what happens in the reality. We also see that percentages are very low since the risk is calculated on a very serious condition.

In the following snapshot I tried to draw a red line which could be an alternative fit of teh data, with a non-null intercept of about 2% risk, and this would take us to zero risk at a value which may be of about 20-30 mg/dL.

 

[Ron Put]

On 4/24/2023 at 8:48 PM, IgorF said:

I think the explanation is in dissonance theory - the more we invest in something the more we tend to justify this something and for the things to work at best we have to first convince ourselves.

Fair point. But I did a couple of searches and based on what I found, I am more inclined to assume that it's all business for Attia, with a strong and increasingly more polished marketing strategy built on his rather engaging persona. The Drive is part of it. I read and watched some of his old stuff too -- I didn't realize he got on the high-fat promoting bandwagon way back when Atkins was still alive. He's been promoting high-fat for so long, that he can't back down without destroying his business. I also thought that he was a practicing physician, but he actually runs a concierge medical service that charges well-healed metabolically diseased people $90k-160k each to stick a CGI on them and run them into the gym, while keeping them on what is essentially the old Atkins diet. And pump them chockfull of pharmaceuticals and then look like a hero because their numbers improve. That's why he pushes Apo B rather than LDL-C, because his patients are metabolically screwed up and he wants them to focus on particles, which in the obese I guess makes sense, but not in the healthy.

Overall, the more I learned about Attia's history before The Drive, the more my respect for him diminished. I have always disagreed with "diet doesn't matter" take, but now it makes some sense to me, from a purely business perspective.

[Ron Put]

On 4/25/2023 at 4:24 AM, mccoy said:

not everyone is so lucky as Ron to have optimal metabolic parameters and this is a war where the enemy chiefs are the four horsemen of death

Thank you, mccoy. I am flattered that you think that I am lucky, and I am sure I am, as many here are, compared to people who have real health issues.

But the best of my numbers had little to do with luck, but mostly with some significant changes in my diet (and to a much lesser extent, exercise). I was already vegan, as you you may know, but my cholesterol did not drop to its lowest points until I removed olive oil from my diet. I was consuming pretty liberal amounts of it (yes, extra-virgin), and when I stopped it, my total cholesterol dropped by 40 points, and my LDL by about 30+. My insulin also dropped to the low end of normal. My weight has been constant.

I am going to test again in a month or so, although the last week I've had to go to dinner and I've had a few greasy vegan meals, and a few rich but delicious vegan deserts, so I expect those to have some impact. But I have to be social, and unfortunately it means eating, even if I no longer feel the mostly self-imposed pressure to drink socially.

Edited April 26, 2023 by Ron Put

[Ron Put]

This is a vey old video that popped up that discusses some of Peter Attia's theses. Some of the stuff he no longer talk about, and the narrator is not all that polished, but many of the points are still valid today, and reflect my objections too. There is a brief discussion of Apo B too.
 

 

[IgorF]

Hm,

after some thinking about ldl-c and ldl-p I could say the logic on focusing on p is like this:

- particles number is considered a primary thing that forms the risk - it is a construct that is capable to reach an unexpected place and anchor there, this is relatively easy to manage quantitatively from different perspectives

- the chole cargo in these particles could probably make a difference - if the molecule itself can bind somewhere in the area of landing with some probability then the more chole molecules a unit delivers - the more additional risk for the next unwanted things

So with this logic both p and c should be taken into account. But p will "lead" somehow an assessment because it is the first event in the chain. Maybe in all the data available is already an aggregated coefficient available to create a linear estimator formula, but I am not sure that this idea worse to spend extra effort - I saw in many places that plaques are very different and unpredictable, so the c parameter could mean a very wide range of risk and this will make it less usable.

I am just speculating, trying to simplify the things to a model that could be used for myself.

 

Br,

Igor

 

EDITED to add.

the first study brought by google to me (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1768597/) list the plaque stability factors like:

• increased lipid content (> 40%)
• reduced collagen content in a thinned fibrous cap
• increased inflammatory cell infiltration, commonly macrophages
• increased expression of matrix degrading metalloproteinases (MMP)
• reduced expression of tissue inhibitor of MMP (TIMP)
• increased concentrations of macrophage colony stimulating factor (M-CSF)
• haemodynamic shear stress.

 

Asked ChatGPT on it:

1. Size of Plaque 2. Amount of Calcium in Plaque 3. Thickness of Plaque 4. Degree of Inflammation 5. Degree of Fibrous Cap Thickness 6. Degree of Lipid Core 7. Proportion of Smooth Muscle Cells 8. Degree of Neovascularization 9. Proportion of Macrophage Cells 10. Proportion of T-Cells

For Smoking, High Cholesterol, Diabetes, High Blood Pressure, Lack of Exercise, Age, Family History, Diet High in Saturated Fats, Stress and Obesity, research suggests that each of these can increase the risk of plaque vulnerability by between 10-30%. For Size of Plaque, Amount of Calcium in Plaque, Thickness of Plaque, Degree of Inflammation, Degree of Fibrous Cap Thickness, Degree of Lipid Core, Proportion of Smooth Muscle Cells, Degree of Neovascularization, Proportion of Macrophage Cells and Proportion of T-Cells, research suggests that these can respectively increase the risk of plaque vulnerability by between 5-15%.

 

No idea about reliability of this answer, but let's assume it is an additional risk estimation coefficient of 1.2 to the ldl-p if there will be discovered that a person has low p but higher c than the median expected for such p. If there will be much higher c then a genetic factor perhaps is in effect and that is another story.

All the other things on the list are also widening the model off course.

 

Edited April 26, 2023 by IgorF

[Ron Put]

19 hours ago, IgorF said:

after some thinking about ldl-c and ldl-p I could say the logic on focusing on p is like this:

- particles number is considered a primary thing that forms the risk

Not necessarily true per se. As the video above mentions regarding APO-B, it becomes primary only if there is a discordance. Otherwise, the studies are inconclusive, which is why it is not routinely tested in the US. My own physician, who indulges my sometimes excessive testing, told me exactly this when I first requested APO-B -- that I am metabolically healthy and total and non-HDL cholesterol are more important in my case, as there is no likelihood that there will be a discordancy. And he was right, of course, as studies show discordancy within a few years to a decade or so after one becomes metabolically diseased.

But Attia, Dayspring and a bunch of others are by far the most prolific and vocal on social media, because LDL-C is often a problem for those on high-fat diets who are often metabolically compromised, so they keep pushing the focus on APO-B. Pharma pushes this as well, as Attia's message drives sales.

Statins have their benefits in diseased people, but IMO it's idiotic to suggest that healthy people take them so that they can indulge in a bad diet.

[IgorF]

Hm,

this is interesting, relatively large study on swedish data for mid-age lipids and all cause mortality with 25 years follow up

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8709841/

from their data the best apoB is in the mid of the lab's normal ranges, 1.1-1.15 approx.

But this is for normal people with normal further destiny.

While I am also sceptical about Attia's idea that apoB is virtually useless in functional perspective and forcing it down to 20 in a healthy person is a thing to try (maybe it is. maybe it is not, too little data and probably will not happen in my time) I think there should be expected perhaps a shift to a bit lower value for people on even mild CR, just because of lack of materials to build it up. No idea if it is about 0.6-0.7 or rather 0.7-0.9 range, hard to guess.

In any case - this study should be an argument to care less about apoB aggressive lowering if there is no other bad metabolic parameters.

 

Br,

Igor

Edited April 27, 2023 by IgorF

[mccoy]

23 hours ago, Ron Put said:

Thank you, mccoy. I am flattered that you think that I am lucky, and I am sure I am, as many here are, compared to people who have real health issues.

But the best of my numbers had little to do with luck, but mostly with some significant changes in my diet (and to a much lesser extent, exercise). I was already vegan, as you you may know, but my cholesterol did not drop to its lowest points until I removed olive oil from my diet. I was consuming pretty liberal amounts of it (yes, extra-virgin), and when I stopped it, my total cholesterol dropped by 40 points, and my LDL by about 30+. My insulin also dropped to the low end of normal. My weight has been constant.

Of course there must be personal effort on top of genetic luck, unless we are dealing with the absolute outliers who are ultra centenarians, who only need their exceptional genetic luck.

Also, as good as yours, and my numbers can be, in the framework of zero risk they are simply not good enough. I don't say that I'm convinced to take statins, but the logic is all there, zero CV risk requires exceptionally low ApoB/LDL numbers and these are reachable only by pharmaceutical interventions.

Now, we may reason that we are at a very low CV risk level, then we don't need to take hazard level to zero and risk the side effects of statins. But the potential side effects are visible on analyses, so it sounds a zero-loss strategy anyway, except that it involves additional  time and effort and cost.

Nearly zero-risk may be determined by regular CAC and coronary angiography with contrast medium. I'm not too eager to undergo those exams...