Keto Cholesterol study SHOCKS scientific community | LMHRs & heart disease

A lot of you guys asked me to go over this recent study on low carb diets, ketogenic diets and plaque and heart disease so I went over it really carefully, I spoke with the senior author, we're going to address a lot of the questions that have been popping up. So this was a study where they recruited 100 participants on ketogenic diets, very low carb diets, average age 55 and these

people had a big increase in their LDL cholesterol levels when they went on the diet, in fact they had to have an LDL of at least 190 to be included, normal is usually under 100, this is milligrams per deciliter, and their average LDL was actually 250, 254, so extremely high LDL levels, and they

also had to have no other major risk factors so no hypertension, no diabetes, no FH (familial hyper cholesterolemia), so no genetically induced hyper cholesterolemia. The idea is that their high cholesterol is induced by the diet and they also had to have low triglycerides and high HDL

cholesterol, and these are metrics that reflect insulin resistance so with these ranges that they used you're basically choosing people that don't have insulin resistance. So the idea is pretty simple, here are these people with diet-induced extreme elevations in their LDL cholesterol but no

other major risk factors, let's see what happens to their arteries, and specifically they looked at their coronaries, so the little arteries feeding blood into the heart muscle, and they imaged those arteries before and after a span of a year using a technique called CTA, computed tomography angiography, so this is a technique that can image your arteries and it can pick up both calcified

and soft plaque. So one limitation of the study is the scale, one year for a chronic disease is not a very long time and 100 people, not a large study, but the main limitation is the lack of a control group, so it's just an observational study of one group of people prospectively over a year,

there's no other population running in parallel, there's no randomization or intervention. This

doesn't mean it's not useful, sometimes in some communities there's an idea that observational studies are junk science, they don't tell us anything, only randomized trials matter. None of that's true, observational studies can provide interesting information

matter. None of that's true, observational studies can provide interesting information but depends on scale and it depends if you have a reference group internally or not so these are obvious limitations that we have to bear in mind. Okay so what happened? If you've been following the soap opera on social media around this study you probably heard a lot about something we call

primary outcomes, so what is that? When you set out to run a study in human beings it's not random, you decide what you're going to measure, so it might be mortality (number of people who die) or heart attacks or in this case size of plaque, and depending on what you want to measure that determines the entire structure of your study, how many people you need to recruit,

how long you need to follow them for, because you need to have what's called statistical power, basically if there is a change in your parameter of interest you need to be able to pick that up statistically. So the primary outcome determines the design, the primary outcome is the thing we're

statistically. So the primary outcome determines the design, the primary outcome is the thing we're most confident in when it comes to interpreting a study, we can also then ask other questions and look at other things like secondary outcomes or things that weren't even predefined as outcomes but our confidence level is lower for those. And also important and convenient is that science is

very organized and so these protocols for human studies are usually pre-registered, so they're submitted to a database and so you can look up the protocol before a study is published or even running and you can see what they set out to do and what their defined primary outcomes are, so in this study their pre-registered primary outcome was the change in soft plaque over a year in this

population. Soft plaque is the vulnerable type of plaque that can burst and cause heart attacks

population. Soft plaque is the vulnerable type of plaque that can burst and cause heart attacks and strokes so it's a relevant measure to look at. So their results are shown in this figure, each line here corresponds to one participant, on the left is before the one year, on the right after one year, so you can see the trajectory, most lines seem to tilt up so in general it

seems that soft plaque appears to be increasing in most participants, to different extents, but this graph is a bit crowded, the lines kind of overlap, especially at the bottom, not super easy to see, this one is easier to see and it's basically the same data, same participants but here each person is one dot, so the line is zero, no change, stable plaque let's say, under the line would be a net

negative, so a plaque shrinking, a plaque reducing size, over the line would be plaque growing, so yeah wide variation in size of change but vast majority of people seem to be moving in the direction of growth, of progression of plaque, and the most important thing to remember is this is a follow-up of one year, when it comes to chronic diseases like heart disease time is

the most crucial factor so we have to imagine this accumulated over 10, 20, 30 years. Now,

this is also showing their ApoB levels and we'll come back to that. So these data surprised me a little because with any risk factor I would expect to see a chunk of people, maybe 30, 40% of people who just don't have the susceptibility, right, genetically they just have great genetics and they can handle, whether it's smoking or whether it's obesity or whether it's high blood pressure,

people who just, even though they have the risk factor we don't see the disease developing, and so here seeing that 90 to 95% of people seem to have some plaque progression, with differing degrees, that surprised me a little bit, at least by this measure that they used, we'll see if that pans out in future studies. Now, a very important reservation, we can't say based on this study

alone that it's the diet causing plaque growth or that it's the high LDL causing plaque growth, we can't make that claim because this is a study without a control group so we don't make cause and effect claims from a single arm observational study, especially with 100 people over one year, I think that's a mistake and we'll get back to this as well. So this is the main finding,

this is the primary outcome of the study, plaque progression over one year. Looking at the figure most participants seem to show some degree of plaque growth, one some plaque regression and three or four are on the line so stable, no growth and no reversal. So what's the average? What's the

average value for the entire population? So that was not reported, it's not mentioned the average, it's not mentioned any statistics like P values before and after for this primary outcome change in soft plaque, so this is an obvious thing, a lot of scientists on social media complained about this and asked what's going on, what's the number, what's the primary outcome, it should be

there. So I asked Dr Budoff, the senior author who oversaw the study, we talked, here's what

there. So I asked Dr Budoff, the senior author who oversaw the study, we talked, here's what he had to say. Then on primary outcomes I know this has been rehashed on social media, we don't need to spend too much time on the non-reporting like numerically of the primary outcome, I think at this point everybody agrees that should have been some form of a table or something like that,

it's not the end of the world... It is in the paper, you know, you're, you're using a... that's

not the final paper, the final paper is being submitted today and it will have non-calcified plaque volume in there, so it's a, I think some of the criticisms are premature and I blame the people who, whoever... they uploaded a preliminary paper, not the final paper, or Elsevier did not

upload the final paper, the final paper does have, and it will come out I think today or tomorrow, non-calcified plaque volume in the methods, in the results and in the conclusion. Okay. There

was absolutely no version of the final paper that doesn't have all of that information, that was, it was a an editorial issue, the editor-in-chief wrote a, is writing a corrigendum to explain how

this was a slight error and it is, it will be reported in the first and only paper published from this cohort will include all versions of non-calcified plaque volume and it's just not, it's just not yet available, that's why I'm worried that there might have been an earlier

version that got out into the mainstream, maybe that was JACC Advances, has put it out too early, I don't know, but I'm still, today I'm still working on the final revisions that are yet to be accepted by the editor-in-chief to be published so this is a pre-draft or a... I don't know what

you want to call it, pre-print, article in press, but it's not the final version but we will have, just to address that question, non-calcified plaque volume is in the final version of this first paper. Got it. Yeah so yeah it sounds like the version that was made available to everyone

first paper. Got it. Yeah so yeah it sounds like the version that was made available to everyone is not... or there are changes being made as we speak, okay. Yes, yeah and to address the issues

is not... or there are changes being made as we speak, okay. Yes, yeah and to address the issues that were raised, but the paper will include all of those variables upfront in the methods, results and conclusions. That's good news. So it seems according to Dr Budoff that the wrong

version of the paper has been released and been available to everyone for the last week or so, regardless of how that happened, what happened, what went wrong, people have been at each other's throats essentially on social media over the study and the many problems and the many errors that people have been pointing out, it's strange because from what I've seen the authors have been

trying to put out fires for like a week or more now with all these complaints and I haven't seen anyone say "Oh this is the wrong version don't worry about it." You know, "another version is coming out, chill". Haven't seen anyone say that, actually in general the tone has been kind of defensiveness and doubling down and just kind of saying "No, the paper's fine you guys don't get

it." That's the general tone of the communication that I've seen from the authors so far but anyway,

it." That's the general tone of the communication that I've seen from the authors so far but anyway, moving on from this, a new version is coming out, we'll see what that looks like. After

all that pressure and people asking over and over "what's the primary outcome?",

the first author of the study came out on Twitter and he released a number, he said "this is the median soft plaque increase over the year for this group", and he cited a number, 18.8 mm3, so that number's been going around for a week now, I've seen dozens of scientists looking at that,

comparing to other studies, doing all kinds of graphs, but when I asked Dr Budoff about this number he essentially disavowed it. And I don't even know where those numbers come from because I'm looking at the paper and I'm looking at the raw data and I don't see 42% or 18.8 mm3. Yeah those are not in the currently available version, that's what I'm asking. Okay,

I'm saying, but I don't see it in the, right, but then, but you're quoting them so they must be available somewhere or somebody's making them up. Your author on Twitter said it was 18.8 when people kept asking what's the primary outcome change, he said it's 18.8 mm3 of soft plaque

over the year. Do you know who said that? The first author, I forget his name. Okay,

all right, well, he's not allowed to do that and I'm not on social media to debate or answer those queries but my statistician does the math and my statistician hasn't released a number that's in

public so I don't know where he got that number, okay but I don't believe it's that number but I don't know, I don't have the final draft yet, we are literally working on it... we're waiting for the proofs, we don't have the proofs yet from Elsevier, this is very premature, the proofs

haven't been approved yet, I haven't approved any version of the paper yet so this pre-draft or this draft is incomplete because I haven't gone through it and approved anything yet, this is, the senior author will proof the final draft and correct any mistakes, we are certainly taking into

advisement issues that were raised to the journal or to other authors but the first author should not and could not be putting out numbers that are not in the paper and I don't know if he has the right numbers because I don't think it came from my statistician. Yeah this is why I'm asking you

these questions, to get your clarification so I don't say anything that isn't accurate, that's my main concern. Yeah I´m just telling you I don't believe it's that number and I believe that, we

main concern. Yeah I´m just telling you I don't believe it's that number and I believe that, we had a a meeting, I don't have the number in front of me because it's not yet in the paper but I do believe that we will definitely report the plaque volume changes in a percentage and an absolute

number in the final paper. Okay. And I'm not aware of what was put out on social media, to be honest, I apologize, I'm just... No problem, yeah, no worries, it's good to clarify. So we'll see what's going on with that, what is the actual number, the actual primary outcome that's coming out in the

revised version but if we look at the figure, just figure 1, that red line is the median before and after and the median increase and you can estimate what that is and smart people have done it, Nicola Guess in her analysis of this study which I highly recommend you check out and I'll link it below, she did what any smart person would do, first she complained that this wasn't available in the

paper, the number, but then she just blew up the figure and she measured it with a ruler and you can do that easily because the axes have units, and she said "this seems to be about 20 cubic millimeters", and in fact the first author went on Twitter and said "Yeah it's 18.8". So it seems

to be in that ballpark at least, unless the whole figure is wrong but we'll see what transpires. I

know this whole thing can feel very frustrating, it's unfortunate that it's gone down like this so I'm trying the best I can to provide some clarity and this is why I wanted to talk to Dr Budoff to get some insider information on what's going on behind the scenes and so I appreciate Dr Budoff coming on and weighing in, we'll see how things develop. Now, the text of the paper

describes this, these figures and these data, in a very strange way, it says "most participants presented with stable NCPV". NCPV is non-calcified plaque volume, so soft plaque, essentially, and so this doesn't seem to match the figures, the lines don't look flat, they mostly seem to tilt up, the

dots seem to be overwhelmingly above the line, and then it gets stranger because the text continues "with one participant exhibiting a decrease in soft plaque", so that's this guy down here, they're highlighting that and they're calling this a decrease but all those dots above the line are

stable, so this jumped out at me immediately, this looked way off, I didn't want to just bash this, that's easy to do so I asked Dr Budoff about this as well. It says "most participants presented with stable soft plaque", that doesn't seem to match with the figures, maybe this is going to change?

Can you read, I don't know what, what sentence that... It says "most participants presented with stable non-calcified plaque volume". It says "most participants exhibit a total plaque volume of..."

oh I see, here, got it, I think they're, they're saying most participants that did have stable non-calcified plaque volume... yeah I don't think it's written very well, and I guess we'll have to make that modification. Okay. The point here is that the participants that did have stable

non-calcified plaque volume... it's just a poorly written sentence I don't know what to tell you, I don't even know what they're trying to say, I don't understand the sentence to be honest so it'll be changed. Yeah okay. Yeah this is changing. Yeah we don't need to spend too much time on it, it just jumps out right away because looking at the sentence and then looking at the

figure it doesn't seem to match whatsoever, the figure if we look at, the easiest one to read is actually the figure 2B, what it looks like is 90 plus% of the dots are in the direction of growth, one is a reduction and there's maybe three or four that are on the line of no change. This

is the figure that's available to everyone. I don't know if. Yeah I see figure 2b. Yeah 2b.

Yeah so I mean yeah the version that's available to everyone that everybody's been criticizing, basically that sentence doesn't match this at all, it just seems really strange, maybe there was a mistake with the, again, with kind of the writing or something but yeah this, I mean this looks like overwhelmingly there's growth, to varying degrees of course, maybe one regression and a couple that

are stable but 90 something% of the participants seem to have a growth of plaque and that's not kind of explained anywhere in the text and then a lot of the messaging on social media also has not emphasized that whatsoever, kind of the opposite, it has not talked about this and that's one of the concerns that I've seen kind of voiced over and over, but yeah if you guys are working on a

revision this would be good to clarify. So, but yes, let me understand what the... yeah

what we're, what the criticism is or what the... Yeah the criticism, like when I read it the text says "most participants presented with stable soft plaque" but the figure shows over 90% seems like growth. But talking about presenting with soft plaque has nothing to do with growth,

presenting with soft plaque means what's on the baseline scan. With stable. Presented with stable soft plaque. Presented with, that means the first scan, presented means scan number one, I'm not

soft plaque. Presented with, that means the first scan, presented means scan number one, I'm not sure how else to read that. I don't think... I don't know how to read it differently... the

rest of the sentence... perfectly clear. I'm reading it, i'm reading it. Okay the rest of the... Presenting with, presenting with is the first scan, right, that's what present means.

the... Presenting with, presenting with is the first scan, right, that's what present means.

I don't think so, I think it's referring to the change because it's pointing to figure 1 and B and then if you continue the sentence it says "with one participant exhibiting a decrease in soft plaque", right, so it's referring to the change, it's highlighting the one guy that's below the line but calling everybody else stable, it looks incredibly strange to anyone...

Yeah I think that's, I think they were trying to talk about the the baseline presentation, I wrote the group to clarify that sentence because I don't understand it exactly either but I don't think that was the intent was to say that they didn't have progression but I I'll have to go back yeah. It's good news that this is being rewritten, it's a sight of relief. Yeah I wrote them, I wrote

yeah. It's good news that this is being rewritten, it's a sight of relief. Yeah I wrote them, I wrote them this exact sentence and said I don't fully understand it to be honest, they talked about the mean change which was 0.8% and "most patients had minimal changes" maybe is what it should say but

there certainly, I'm not sure what they mean by "presented with stable non-calcified plaque volume" to be honest or what the definition of that even is because that's not a definable term, what stable plaque is, does that mean it only went up by 1% or it didn't go up at all or it

went up by 3%, what's acceptable or stable is not a term that we typically use so I thin we would say "most patients had a minimal plaque changes", perhaps, or minimal increase would be a reasonable terminology but I'll definitely change this for sure. Okay. Okay

they also presented their results in a different way, this is called a total plaque score or TPS and this is basically a semi-quantitative measure, basically a human observer looks at each plaque and splits it into buckets, small medium or large, as opposed to those measurements we looked at of actual sizes of soft plaque, that's all done with AI, kind of computerized method,

and when we look at those plaque scores it looks different from the measurements of soft plaque, so some went up in score over the year, six went down and many have stayed in the same category. So a couple things about that, one is that this is a less sensitive process and you

category. So a couple things about that, one is that this is a less sensitive process and you can have plaque growth and the plaque can still be in the same category because these are not continuous variables, right, it's three buckets essentially, especially if the plaque is small, it can still grow substantially in percentage but still be in the same bucket, so that's one caveat,

and I asked Dr Budoff which technique he favors if they disagree and he said the quantitative one, the one that measures actual size of plaque, in this case size of soft plaque is more reliable, more precise. So based on the information we have, this is where we are and I'm giving more weight to

more precise. So based on the information we have, this is where we are and I'm giving more weight to the actual precise measurements of soft plaque in the cubic millimeters that we looked at. Okay the

next thing the authors did is, because there's no internal control to compare this group with they compared the results to other populations, other studies that already exist out there, that's smart, I think that's what I would have tried to do, nobody's pretending that that's the same thing as having an internal control, of course it's not but as a first pass it's what you'd ask,

how does the behavior, how do the results, the plaque growth in this population compare to other populations that are published? So they compared the plaque progression in this population to four or five other cohorts that exist already and they basically conclude that they're comparable, the rates of plaque progression are comparable, so in the same ballpark as those other studies. Now,

I don't find this very reassuring because a lot of these populations are kind of typical westerners: overweight, blood pressure not great, cholesterol not great, insulin resistant, all these things so having comparable rate of growth to these people, and we know the primary cause of death in these populations is heart disease, it's not the most reassuring result. On the other hand, in these

populations there's always a chunk of people that are on statins and other lipid-lowering medications and we've known for many years that statins can slow down and even stop plaque growth so it introduces another confounder, right, it's not quite apples to apples because the folks in the keto group are not medicated, they are statin naive and treatment naive as far as lipid lowering

medication so it introduces a confounder, so I looked for other studies where the participants are also not taking statins which has more... it's a more interesting comparison, right, more apples to apples. I found one with fairly healthy individuals, for western standards anyway, this cohort is called nature-CT, the whole aim was to evaluate the natural history of heart disease,

of plaque, of atherosclerosis in a healthy population, so they had zero diabetes, zero statins or any lipid drug actually, their age was identical to the keto group, 55 years old average, and this nature-CT study was conducted by the same institute at UCLA overseen by Dr Budoff as

well and they use the same technology as the keto study, this Clearly technology, that AI driven technology to score soft plaque so to me this is the best comparison, the cleanest comparison, you have one population that's as healthy as you can find in these studies, in Westerners, not a ton of other risk factors, not perfect but as good as possible, no statins,

no diabetes, and then you have another population where they're hand chosen to have no diabetes, no high blood pressure, all these things, pretty clean but then sky-high cholesterol, this is what we want to know, is the hypercholesterolmia in these folks causing problems in the absence of other major risk factors? This has been as far as I know the motivation for this project from the

get-go. So I asked Dr Budoff about this, he agreed that this nature-CT study is a good comparator,

get-go. So I asked Dr Budoff about this, he agreed that this nature-CT study is a good comparator, in fact he says they are working on a paper where they're going to use this as the comparison for the keto group, I'm not sure why this wasn't shown in this initial study and they used these other studies where there's all kinds of confounders and they themselves have been,

the authors, several of the authors on social media have been kind of complaining that it's not an apples to apples comparison because of the statins, why use it in the first place? Anyway,

we'll find out what the result of this is later but just with the currently available information, because the nature-CT, some of the results have been communicated in a meeting last year, pretty recent, they report that the progression of soft plaque was 4.9 cubic millimeters annual median,

compared to that 18.8 on the keto population as reported by the first author, but again Dr Budoff disputes this, but unless the figure is completely wrong it's going to be in that general ballpark, we'll see. If this pans out in general it's a bit concerning, this is a 3.8fold faster

we'll see. If this pans out in general it's a bit concerning, this is a 3.8fold faster progression of soft plaque in the keto group compared to a population of Westerners that is reasonably healthy, without a ton of risk factors and that doesn't have that sky-high cholesterol, that sky-high LDL, and that is not on statins, important, right? And like I said they're not

perfect, 24% still had high blood pressure so they have some issues so maybe with an even healthier population we'd see even less plaque progression, or no plaque progression, but this is the cleanest study that I'm aware of, the cleanest population to do this comparison so we'll see what happens with that. Okay the last thing they did in the paper, remember there was a lot of

variability in how much plaque was progressing in all those folks, remember all those dots, so they asked what explains that variability, so they found that the amount of plaque at baseline correlated with the speed of plaque progression, so people who had more plaque to begin with tended to have faster plaque progression which makes sense and is actually a common finding in these

imaging studies, that's been known before. By the way when we look at the results plotted by calcium score if you look at the folks who had zero calcium score at baseline, when the study started, there's a huge spread in how much soft plaque is growing, all the way from zero, no plaque growth, to very high levels, 50, 100 cubic millimeters a year, so caution with the calcium score,

we've talked about this before, I think the calcium scores are useful, I've gotten them myself but a zero calcium score I always use caution, especially in a younger population like 40s or 50s, zero calcium doesn't mean zero bla plaque and it doesn't mean zero risk, especially long-term.

On the other hand they found no significant association between the level of LDL exposure or the level of Apo B at baseline or the changes in Apo B during the follow-up and the speed of plaque progression, now I've seen people on social media say that "oh so this means cholesterol doesn't matter on low carb", "oh this means if you go on a keto diet and your cholesterol goes up it's okay,

the study shows that", we don't get that information from the study, in my opinion that is a wild overclaim, like I said, we don't make these cause and effect inferences from a study without controls, we don't have a control group with normal cholesterol, we don't have a control group on a different diet. So I have essentially two issues with this analysis, the first is that

I'm not sure that the study is powered for this analysis, it was not pre-registered so this is what we call an exploratory post hoc analysis, you think about doing it later on but the study wasn't designed to do it so you may not be statistically powered to do it, you may not pick up an effect that may be there, and second, the study does not look at going from normal cholesterol to high,

everybody had high cholesterol to begin with, extremely high, that's the inclusion criteria, that's how they were chosen in the first place. In fact their average ApoB was like 185, 99th percentile of Apo B in the US as far as I remember is about 160 so their average Apo B is

significantly higher than the 99th percentile so very extreme range of exposure. So what happens in these extreme ranges may not reflect what happens in more common ranges and I'd expect that for all kinds of risk factors, I expect going from no smoking to three packs a day to make a big difference in risk but going from five packs a day to eight not so much, if I find out that there's

not much additional risk here that wouldn't blow my mind. Another example, glucose raises risk heart problems but when you get to crazy high ranges there's not a big difference if you go even higher, the effect kind of plateaus, so in my opinion we should never extrapolate from an extreme range of exposure to the entire spectrum, the question that most people want answered is

what happens if I go from normal levels of cholesterol or Apo B to high, and where is my risk minimized? This study cannot address that, it doesn't look at that at all, by design. Now,

risk minimized? This study cannot address that, it doesn't look at that at all, by design. Now,

I ran all of this by Dr Budoff, he did not agree with this idea of the plateau, he does not believe that that's a possibility, mainly because he says we always see a linear effect between LDL and plaque, the higher the LDL the faster the plaque grows even in participants with FH which have very high cholesterol levels and he says that even there we tend to see a linear effect

so he doesn't buy the plateau possibility, whereas the issue with underpowering he agreed could be a factor and a larger study or a longer study could possibly in the future give different results, so we'll see what happens with that. Basically my thing is, an exploratory analysis with 100 people, no control group, I think we're extremely cautious with something like that, it's maybe

hypothesis-generating, it's something we can put in a paper, in the end, and say "oh we found this, suggests that, maybe that", but we don't hype that, and this result has been hyped ad nauseum on social media, in fact it's been pitched to people as the main finding of the paper and in the paper itself, the paper is written, the version that we have access to right now,

the whole paper is written around this result so I disagree with that entirely. In one of the last sections of the paper the authors write "our data should be reassuring for these patients and their physicians". Now, maybe this will change in the revised version of the paper but the data as I see it does not reassure me and it wouldn't reassure me if I was in the skin of these guys. 90

to 95% of people showing plaque progression, if we look at average of the population it's in the ballpark of sick Western populations, we compare to westerners that are not that sick, it seems several fold higher, none of this seems very reassuring to me. I know there's heterogeneity, not everybody's at the same level of risk but as a rule this doesn't seem very reassuring to me. Now,

we've seen general outrage and complaints about the study from scientists on social media, an onslaught, I've honestly never seen such an intense and almost universal reaction towards a study that came out, and actually some of the most aggressive takedowns that I've seen of the

study have come from people, from scientists and practitioners who prescribe low carb diets who eat low carb diets like Dr Nicola Guess, like Dr Ethan Weiss, and I think that's because they're frustrated that they understand these diets have clinical application, have use and have serious science behind them and they want to see these findings, they were excited to see them but they

want to see them communicated objectively and honestly and in a way that makes sense and not butchered like they have been. So people are not opposed to the project, to this being measured, I'm supportive of this being measured, I think it's interesting to see what happens, I think it's good to measure what is happening to these people since they're doing this out of their

their own free will, I am not supportive and I am not impressed by how the results have been communicated to the public, particularly on social media and now even this version that was released, maybe by by mistake, and this goes back to a year or two ago when the study was not even published,

wasn't even running, just hyping this to the public continuously, constantly dog-whistling that it's okay to have sky-high cholesterol, ignore your doctor, abandon medical treatments, incredibly reckless, in my opinion no regard for human life, that should not happen, in my view the way this study in general and these results have been communicated to the public on

social media is a great example of how not to do science communication. Here's an example, one of the authors on a Facebook group dedicated to folks who have these sky-high cholesterol levels, he's giving them the news of the study, he talks about all kinds of details, how the participants were recruited, he talks about that exploratory analysis, the LDL and the ApoB and the plaque at

baseline, there's not one word about the primary finding, the primary outcome of the study, the fact that the majority of participants are seen to have plaque progression, and I've seen many others like this, posts and videos and interviews on social media, this has been kind of the tone of most of the communication of the results of this study by the authors. Do you think these people in

this Facebook group with astronomical cholesterol level who have been waiting for this study, who paid for this study, this study was funded by asking precisely this community for contributions, do you think they might want to know that over 90% of people are seen to have plaque progression to

varying degrees, do you think they might want to hear that the average is in the ballpark of Western populations and if we compare it to Western populations that are healthier we see what seems to be severalfold higher progression of soft plaque? Do you think they might want to know that?

Do you think they have the right to hear that information from a study they paid for to make informed decisions? Telling them only that the association with cholesterol was not significant

informed decisions? Telling them only that the association with cholesterol was not significant telegraphs to them that they're fine, that this thing they've been worried about for years, their sky-high cholesterol, is not a problem, you're probably safe, that's the takeaway from this type of messaging and that's essentially the opposite of the take-home message when you look

at the data itself. And in fact I've seen tons of influencers and media headlines and just members of the public on social media that essentially got this message, so it's fine, hypercholesterolmia is fine on a low carb diet, they're not at higher risk, I've seen headlines like that, that's in

a nutshell the opposite of the core information that I get by looking at the data itself. Guys,

based on everything we know in this field going back decades, I wouldn't keep any of these risk factors elevated, not high blood pressure, not high glucose levels, not smoking and not ApoB, you couldn't get me to do that for all the money on this planet, and that's independent of the diet, high carb, low carb, intermediate carb, high fat, low fat, i wouldn't do it on any diet,

and we have so much knowledge and so many tools to avoid this, we have a video going over randomized trials showing reduction of plaque, shrinking of plaque with different diets, you can do it with Mediterranean diets, you can do it with DASH diets, if you want to be on a low carb diet, if you prefer to be on a ketogenic diet you can do that without jacking up your cholesterol,

we've known how to do that for years, we have a recent video looking at a study where they put the participants on a ketogenic diet, very low carb, sky-high ketone bodies, no dysipidemia because they designed the diet to avoid that, you just replace some of the butter and the lard with olive oil and some of the fatty meats and bacons with some lean meats like chicken breast or some

fatty fish, this is not rocket science, we've known how to do this for years. We've also known that lipid lowering treatment slows down plaque growth, stops plaque growth or even reverses plaque if the risk factors are pushed low enough, and it doesn't have to be statins, we now have four or five different drugs that do the exact same thing, it's not about the specific drug,

it's about how low you push the risk factor. We have so much knowledge on how to avoid this, why are we still talking about faster plaque growth and not quite as fast, this is all in the rearview mirror, nobody needs to be laying down plaque or walking around with astronomical ApoB in 2025 regardless of the diet you prefer to eat. If you can't normalize your Apo B for some reason,

get the scans, take a look at your arteries and figure out what's going on in your body specifically, maybe you're one of these five or 10% of people who don't have plaque growth, hopefully. And bear in mind, the calcium score may not be enough, interpret that with sense,

hopefully. And bear in mind, the calcium score may not be enough, interpret that with sense, if it's a zero calcium score and you're 30 or 40 doesn't mean you're immune from heart disease for the rest of your life, just bear that in mind. Here's that video on plaque reversal with diet in randomized trials, check that out, and here's everything you need to know about

safe ApoB levels from all the science we have, check those out, I'll see you in there, bye-bye