Dhru Purohit Show - Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman

Episode Date: April 9, 2025

This episode is brought to you by Levels, BiOptimizers, and Birch Living.  Traditionally, elevated LDL has been directly linked to a higher risk of cardiovascular disease. But today’s guest is on a mission to dig deeper. He’s raising both awareness and funding to explore the true relationship between LDL, ApoB, and heart disease—challenging long-held beliefs in the process. He joins us to share the results of his team’s groundbreaking study. Today on The Dhru Purohit Show, Dhru sits down with Dave Feldman to discuss his team’s landmark study on LDL cholesterol and its implications for cardiovascular health. Dave shares the personal journey that led him to fund this research and what it means for how we approach and treat heart disease. He breaks down the surprising findings on how plaque progression really occurs—and the key questions that still need answers in future studies. Dave also outlines the most effective tests to assess your risk, along with how to interpret your scores based on age. Dave Feldman is a software and platform engineer, entrepreneur, and founder of the Citizen Science Foundation. His life took a radical turn upon seeing his cholesterol skyrocket after adopting a ketogenic diet, and he became obsessed with understanding why this is common with those who are likewise leaner and more metabolically healthy. Through a series of self-experiments and partnering with formal researchers, he has since published the “Lipid Energy Model,” which may explain this phenomenon. In this episode, Dhru and Dave dive into: Dave’s mission and journey to pursue answers (00:30) What mainstream medicine believes about high cholesterol (4:20) The keto and carnivore view on cholesterol (6:00) Dave's perspective and his groundbreaking research (7:45) Why Dave’s research matters and its implications for cardiovascular disease prevention (15:57) The factors that led to starting and releasing the study (18:23) The surprising results of plaque progression (28:42) What the results mean on a broad scale and how to configure the right type of diet (35:32) Appropriate testing and optimal score ranges (45:32) Factors that contribute to plaque progression (53:32) Injury to cells and arterial lining—and what prevents repair (1:00:32) The likely responses to the landmark study (1:23:47) Advice on ApoB based on large-scale metabolic health concerns (1:38:32) Critical takeaways (1:42:22) Where to follow Dave and learn about his upcoming movie (1:45:32) Also mentioned in this episode: Plaque Begets Plaque, Not ApoB, JACC Journals Citizen Science Foundation For more on Dave, follow him on Instagram, Twitter/X, YouTube, his Website, and other platforms, such as Cholesterol Code. This episode is brought to you by Levels, BiOptimizers, and Birch Living. Right now, Levels is offering my listeners an additional 2 FREE months of the Levels annual Membership when you use my link: levels.link/DHRU. Make moves on your metabolic health with Levels today. Go to bioptimizers.com/dhru now and enter promo code DHRU10 to get 10% off any order of Sleep Breakthrough and find out this month’s gift with purchase.  Get 20% off your Birch Living mattress during their Spring Event—just head to birchliving.com/dhru today!  Learn more about your ad choices. Visit megaphone.fm/adchoices

Dave, welcome back to the podcast. You are an engineer, a citizen scientist who's on a mission. And today is a very special day because this week you guys have published a groundbreaking first of its kind paper. For anybody who's interested in the idea of, does my diet make me more likely to get a heart attack or does it make me less likely to get a heart attack? Is my diet healthy for my heart? But before we go into the paper and unpack it, tell us about what is that mission that you're on? First of all, I had no interest in nutrition, medicine, even really science that much, as much as I did engineering. And so I've been a software engineer my whole life for the first, let's say, four decades in my life.

And then I'd gone on a ketogenic diet. And going on a ketogenic diet, I just felt great. It was so wonderful. And at the time I was training with running and so forth, I, uh, was setting personal records. I lost a bunch of weight. And I thought I just kind of found the fountain of youth and couldn't stop telling my friends,

especially my family, my dad and my sister adopted at the same time. What happened, though, was while their blood work came back looking fine, including lipids like cholesterol, mine shot through the roof. That ended up changing my whole trajectory, literally for my life for like the last decade. That's what ultimately led me to where I'm at today.

You went on a ketogenic diet. You felt good. most of your blood work look good, except for a few of these markers. What were the markers? And for our audience, that considers himself largely professional amateurs, right? They know a lot about these things. They may not have a degree in medicine. They may not be a nurse practitioner or PA.

They like to know the specifics. So what were the markers and what were their levels for many of us, including myself, who are paying attention to our cardiovascular health? So when you get your quote unquote lipids, the lipid panel has four different markers on it. One is total cholesterol. The second, the one most people are paying attention to is called LDL cholesterol. Often the mnemonic is that it's the L for lousy, lousy cholesterol. Then there's HDL cholesterol, which is the so-called good cholesterol, and then there's triglycerides, which is a measure of fat in the blood.

Usually a doctor is looking at those first two. They're looking at total cholesterol or they're paying attention to. to LDL cholesterol. And the ranges for that, total cholesterol, per the guidelines, they're supposed to be 200 or less. LDL cholesterol is supposed to be 100 or less. And then, frankly, they don't pay much attention to HDL and triglyceride is quite the same.

Now, my historic LDL cholesterol was between 120 to 130. And my doctor was usually like, eh, it's about the average of what I see for an adult male. But it would be nice if it was a little bit lower. But I go on a ketogenic diet, and my LDL goes from that. 120, 1.20, 130, up to 250. So naturally, I'm quite concerned. And my doctor says this is like one of the highest cholesterol I've seen. And I almost never see somebody change to this level of cholesterol. Because usually it's genetic. That's where the tie in with my dad and my sister are relevant.

They go on the same diet, about the same time. They don't see this jump in cholesterol. And that's what got this whole obsession going for me. Before we get into the paper and what questions you guys were answering some of the pretty profound results that you had and unpacking some of the questions that come along with it, I want to actually ask you for a favor because you are so well-versed on this landscape of these different theories and views when it comes to cardiovascular health. So my audience is very well aware of a lot of different people or organizations in health. and they are interested about what is the truth for themselves when it comes to how to pursue down the path of cardiovascular disease. But let's lay the land out a little bit and then we'll get into your theory, your original theory, and this paper that you guys put together.

So give us the view on those panels, on heart disease. What does traditional sort of mainstream medicine throw in like Tufts University, these schools of nutrition, Harvard University, when it comes to high LDL, when it comes to high cholesterol, what is their view of our diets and the risk of cardiovascular event in the future? Without question, the conventional view right now across really every single organization around heart disease is that high cholesterol is high risk. End of discussion. The higher your cholesterol, the more at risk you are.

And you'll often hear phrases like, the lower, the longer, the better. because generally speaking, no matter what, just like a smoker, if you smoke three packs a day, sure, there's the once-and-a-while example of somebody who managed to escape getting heart disease or lung cancer, but as a population, everybody who's smoking three packs a day is at risk, even if they're otherwise healthy in every other respect. And so these organizations, you talked about this landscape, the guidelines are quite clear that if you've got high LDL, you've got to take steps to change it. That's where these ranges come from, like having the total cholesterol under 200 and

LDL under 100. And they'll say that it's better for it to be even lower. And that guides a lot of the food choices, because I'm sure you hear saturated fat can potentially be bad. Why? Because it can be associated with increased LDL cholesterol, and therefore you should eat less saturated fat and hopefully get lower LDL cholesterol. That's the intent.

Now, you have a lot of nuanced thoughts about this, but let's take the traditional or the historic sort of keto, carnivore community, or even the low carb community. What was their view on things? And I know that you share some of those views, but you even have some nuanced views within that. But let's get that more other extreme of the view, right? Like some of the top influencers in that space. What is their view of that same landscape?

At the time that I was coming into low carb, and this is 2015, 2016, a lot of what was being discussed was the particles themselves, getting a more advanced test than a lipid panel I just mentioned, such as an NMR, nuclear magnetic resonance test. And that led to the discussion of the big, fluffy versus small dense particles. This comes back to the work of a scientist called Ronald Krause. and if you've got a lot of these LDL particles, but they're big, they're larger in their size. Generally, they're considered more buoyant and fluffy, and they're considered less atherogenic. People who have this pattern for which there's higher and higher levels of the big fluffy

have what's known as pattern A, but pattern B is where you have more and more of the other kind, which is small dense. And therefore, a lot of people who are low carb, who even had high LDL cholesterol, were saying, well, but I have pattern A. so I don't think I'm that much at risk. But even then there was still a lot of debate.

There are yes, where a number of people were saying, I just don't even care that much as long as I'm Pattern A, I don't care how high my cholesterol goes. There were definitely a lot of people who were saying, well, you know, I could be more okay with my LDL being, say, 180 or 190. I have a problem with it getting up there to say 300, 400, 500. And that was a new phenomenon.

Even within the low-carp community, that was actually pretty new. So let's talk about some of your views and especially in the context of this groundbreaking research, which is out this week. I'm going to do my best to give a very brief overview of what I would call the lipid-aryngy model, which we've now established and published with the enormous help of your prior guest, Nick Norwitz and Adrian Sotomoda. The three of us have actually codified a lot of this into the literature, but this is kind of how it works. We're constantly talking about metabolic health. but what is metabolic health? What actually establishes it? Well, metabolism is that balance, right?

Between enabism and catabolism, you're breaking down and building up. But what we're usually talking about is fuel. So when you're consuming particularly something like carbohydrates, you're storing your fuel as stored glucose, which is in the form of glycogen. That's fine, but that's a small container within your body, whereas fat, we have a fairly large container with regard to our adipose tissue. So if you've got good metabolic health, if you're good at pulling the fuel out and putting it back away again, but you're powered more by fat, what's relevant that fat in the blood needs a carrier.

And the biggest bulk carrier are these complexes called lipoproteins. So that LDL I mentioned earlier, that's short for low-density lipoprotein. So these lipoproteins, if you're trafficking them more in the body, particularly if you have to move more those fatty acids around, It gets a bit complex, but we would argue that cholesterol is ride-sharing in that process in these containers. That's the reason why you're seeing higher LDL cholesterol. Because in short, if I have to release more fat and then replete it back again and after the power my muscles more with fat and so forth, that metabolism, that pulling the fuel in and out, I have to get carried on these APOB containing lipoproteins like VLDL, which remodel to LDL when they drop off their fat. fat-based cargo in the form of triglycerides. So if I'm understanding correctly, you've trained your body if you're on a low-carb diet,

right, or lower-carb diet or ketogenic diet, carnivore diet. You've trained your body to use fat as fuel. And so you just have more fat flowing around the blood and that's going to get picked up in a blood test and it's going to make it look like to the outside, hey, this person could be unhealthy, quote unquote, than maybe they actually are simply because they have a lot more fat flowing around their bloodstream. Almost. This is where it gets tricky because a lot of times when I'm talking about this, folks say, well, wait a sec, the major cargo, the fat that's being carried by lipoproteins

is triglycerides. I mentioned that as part of the panel. But a lot of people go on a low carb diet and this includes myself, would see their triglyceride levels in the blood test go down. So how can that be? If I'm saying you're moving more of these around and you're powered more by fat, well, in truth, the model is positing that there's just more successful delivery. So taking a snapshot of your blood is kind of like taking a snapshot of an active shipping lane that's out there in the ocean, but most of the boats don't have cargo in them. Why? Even though you know they're shipping a lot of the cargo, because they're successful. They're moving it quickly, and the turnover is faster. So when we're seeing the high cholesterol, what we're doing is we're actually seeing empty boats, boats that

started out with a lot of cargo, but are so quickly shipped and taken up by the tissues that are making use of it. That gets us all back to this larger theme of metabolism. Because even if you're not on a low carb diet, having, for example, high HDL cholesterol and low triglycerides tend to be associated with good metabolic health. It's just if you're powered more by carbs, you're shipping less fat, but the turnover of that cargo is still a part of the same story. It's just that if you're somebody like myself or Nick Norwitz or Adrian Sotomoda, you're moving more fat because that's what you're powered by and therefore you have more empty boats. So in a sense, what I'm saying is the LDL are just a lot of empty boats. Let's zoom out for one second as you're building up this landscape,

including your views in it, and then we're going to get to the paper. Why does this question and this topic matter, right? Somebody might be listening today and say, look, I'm trying to eat healthy. I'm not on a ketogenic diet. I generally am aware of not having too many carbohydrates, and everybody has maybe a range of what that is. I try to stay active. I'm trying to build my lean muscle mass so I can make use of the glucose inside of my body. But why does it matter for the person who's listening today who's like, I'm not ketogenic, I'm not super low carb, I'm not carnivore, help me understand why this topic is super important to me. All right, I got a question for you.

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then it's understandable why you may hyper focus on that as being the central thing to change and all of your heart disease risk will follow suit and that these other risk factors are really ancillary, you know, something like blood pressure and so forth, they all come second to cholesterol. Blood pressure, insulin, high insulin. Yep. What else would be inside of that category? What else would you put there?

Well, there's waste to hip ratio. Of course, I'm just, I'm listing off the things that are in metabolic syndrome. There's high fasting glucose, high A1C, but that gets back to insulin resistance. Low HDL, high triglycerides. Yeah. So if you think that cholesterol is the end-all be-all story, then you end up minimizing or deprioritizing a lot of these so-called secondary factors. And part of your sort of thought process is that what if these secondary

factors are way more important than we understand. Honestly, I feel like this shouldn't even be debated anymore. I'm stunned, and I kind of get on a soapbox about this, but I'm stunned that there is so much attention still paid to LDL cholesterol, or for that matter, it's major carrier, APOB, relative to insulin resistance syndrome, relative to poor metabolic health, when without question, poor metabolic health isn't just bad for overall mortality, but specifically to cardiovascular disease. If we're talking about cardiovascular disease risk, that should be one of the first places the conversation starts. Because unfortunately, there are a lot of folks, including some

challenge cases within my own family, who hear, hey, if you get your LDL cholesterol low enough, you're a low heart disease risk. And the data just does not support that. You have to care about being healthier yourself, particularly when it comes to metabolism. Well, we're going to pick that up in a second because I want to get your thoughts on a bunch of things that you shared there. But I think that before I get ahead of myself, let's bring this back to this paper that you and your team have put together that has been years in the making, set it up for us by starting off with the original questions that led to even undergoing this study, raising money from your community primarily to get this thing funded.

and then ultimately it ended up being published this week. So what were some of the original questions that you wanted to explore that helped set up the study and then talk about what is this study and what is it designed to explore? The study centers around a phenotype I had named in an article in 2017, lean mass hyper-responders. So like myself and many others who I was communicating with at the time, we don't just have the high LDL cholesterol. But on top of that, we have the high HDL cholesterol, the low triglycerol. So of course, high LDL is considered a risk factor independently. And high HDL and low triglycerides, they're associated with lower cardiovascular disease risk.

But as I'm sure you see on social media all the time, they're again considered to be secondary, that they're not ultimately going to protect you from sky high levels of LDL. In identifying this phenotype, I went knocking on the doors of lipidologists and cardiologists and research saying, hey, let's study this phenotype. To put it quite plainly, most of the interest is in studying populations that are, already at severe risk, including having these metabolic problems. Well, I just got done explaining the lip-inerogy model with regard to why there might be high LDL from heavy successful trafficking of the cargo of fat.

I would argue that its counterpart known as atherogenic dyslipidemia, where you have low HDL, high triglycerides, is where there's more of a traffic jam. Unfortunately, all of the research is focused there. it's almost impossible to get scientists to be interested in studying, especially prospective studies, on folks who are especially healthy but have high levels of LDL and APOP. But that, to me, is crazy given the fact that you have the variable of interest that we're all focused on right there, perfect for an experiment. So after two years of trying and failing to do this, I said, what the I'm just going to,

I'm going to start my own charity to fundraise for the study that we were. want to have. So the critical question is, are folks who have sky high levels of LDL and APOB, but are otherwise metabolically healthy, are they going to show that association? Is it going to bear out that high LDL will associate with a corresponding increase in plaque? I start Citizen Science Foundation in 2019 and I'm raising money after that point as well as getting together with a protocol team and ultimately we find our principal investigator and Dr. Budoff right here in LA at UCLA, the Alunquist Institute and managed to raise enough money to where we can actually make this study happen.

It was, they said that we could do this with 25, 30 people given just how high their LDL cholesterol is, but I wanted 100. I knew that was ambitious. And I basically was telling the community this at the time that was fundraising. I said, you know, I can cut off at any time, but I estimated it will be about $2,000 per lean mass hyperspotter participant. So at 50,000, we have a number. to go off of, but I'd love to get 100, but that'd be $200,000.

And credit to the low-carb community, they stepped up and put that money together. The key question is that question. But to get the best data, I didn't want to do multi-center either. I wanted to fly everybody here. And another thing that's not normally done in studies is we placed all of the participants in a hotel to spend the night so that they would be rested and so that they're fasting blood work would be complete. So all 100 participants per the study design were flown here, and they got what's known as a CT angiogram. It's a high-resolution heart scan where they actually,

they take them through a CT and they get a CAC test on the first pass to find out how much calcium they have. And now in a second pass, they have contrast dye applied. And that scan is coming at them from all directions to be able to pick up a very high resolution to where you can actually identify plaques of one millimeter cubed one millimeter cubed or even lower in some cases typically what people call off plaque right it hasn't calcified yet although they do look at it's both it's both yeah we're picking up both soft plaque and calcified plaque basically all plaque they get this on their first visit and then they're to return a year later to get a second scam so all participants get a total of two scans, it's a total of 200 scans. Now, after we got that first set of

scans, we've already published data on it. You and I had already chat about it before, including the Miami Heart match, which looked at another study and compared those first initial scans with the Miami Heart cohort. But this was especially of interest was the longitudinal. That's what they call it where you're getting it in two separate points in time. Would we see an association between LDL cholesterol and the progression of plaque at an individual level. Yeah. So basically for these people who are healthy, active in most cases, their blood work all looks normal minus the high LDL, the high APOB. And you talked about LDL in terms of the number. What's considered a high APOB? Is that anything over 80?

Anything over 80, yeah. Okay, great. So like at one point in time, and I'll talk more about myself, I fall in this category. My APOB untreated, and I'll talk about some of the treatments that I decided to go on, my APOB untreated on a low carb, you know, metabolically healthy diet with like an optimal fasting insulin. My APOB was 180 at its highest. That, by the way, is the average.

It's around the average of where our participants is. Yeah. So somebody out there, a Peter Attia would see it and smack you in the face and say, we need to get this lower, you know? the vegan doctors out there that are making the Netflix documentaries are going to be shouting from the rooftops and say, you are killing yourself and you probably already have your heart filled with plaque, especially you've been doing this for five or 10 years. And I think that's the other important thing is that many of these people, they've been eating this way for a while. It's not like

they just started eating this way. How long was the person typically on a more low-carb diet? That's an important question, because our eligibility was they needed to at least have been on the diet and at these levels for two years for baseline. I was stunned to find out that we had over, it was half a decade, half a decade was the average that our participants were at these levels. And naturally, I found that to be very exciting because now we have some fairly strong data, even at baseline of how much their plaque levels would associate. But then we'd also have the progression.

So even though the progression is being measured over one year in the longitudinal, you add that to the baseline of the 4.5 years before that. So this is a long span of time. I also want to drill into something that's kind of important, really also distinguishing the importance of looking at 80 versus 180 because the present lipid hypothesis is not that 180 is about twice as bad as 80. The present understanding is that it's log linear, which is to say with each increase, for example, in LDL cholesterol of. 39 milligrams per deciliter. There is a further increase in risk that continues to go up exponentially. Like earthquakes, right? Yeah.

A six earthquake, 6.3, not that bad. A 7.5s, 8, 9 is like decimated an entire town. Absolutely. And so, of course, there's a clear expectation of an increase in likely plaque for just how high these LDL levels are. I mean, Brown and Goldstein is, their work is. their work is 50 years old at this point, but they had a patient that they describe as pivotal

to their whole research trajectory because she had an LDL of, I want to say it was around 700 and saw rapid development of plaque to where at age three, she had a stable angina. And at age six, she was having mycardial infarctions. It's sad,

but it's understandable. why when they're seeing that association, they're going, wow, this really hits the strength principle of Bradford Hill such that it looks like this really is causal, since after all, she doesn't have any of these other risk factors, right? She's not a smoker. She's not type A, et cetera. So bringing it back to the average levels of our participants,

the average of APOB being 180, this is a very, and this is a wide range. We even had, I think, I think our participant that the highest LDL was close to Bradford Hills, or sorry, was close to Brown and Goldstein's patient because it was, I want to say,

590 LDL? This was one of, this was the outlier on the far edge. But she did not have a high reported plaque at all. She actually, I think, had one of the lowest. So going back to this description that I had,

which is that you had these participants, 100 people that were part of this study, who largely have great blood, work, except for their LDL, their APOB, these couple markers that traditional medicine would say, you're going to die if you don't get this in check. They came in and said, look, I feel good. Many of them have lost weight. Their focus is great.

I mean, we've had on some of the pioneers in metabolic health that have talked about people going on these diets to, you know, address their schizophrenia. Today's national bipolar day, like get rid of their bipolar disorder, you know, symptoms. So people are feeling really good, but they're asking that. question that you asked, which is, is my heart okay? So you took a snapshot in the beginning through this more advanced version of a CT scan, a CCTA, right? That's what it's called. So you're looking at hard plaque, you're looking at soft plaque, and you're getting a baseline. Now take us further to the next snapshots that you did. You said you did one a year later on?

Correct. Yeah. And then was there another one after that or that was the main one, the snapshot after year? The snapshot after the year, it actually completes the full scope of the study. That's what we raise the money for? And so then what did you see for that snapshot in one year's time? And what does that add both in terms of clarity, but also the questions? Because often you'll do studies like this and there'll be more questions sometimes that come along with it. So what were some of the results that you and your team have unpacked that you've talked about in the paper? Well, it's it's right there in the title. So I'll reveal the title.

Of course, many may already know it by this point that plaque begets plaque, but APOB does not. So let me take both of those. The first and most obvious thing is that if there was existing plaque at baseline, it was very correlative with what the plaque progression to be expected would be. So somebody already has plaque before that first snapshot, right? On that first snapshot. On that first snapshot. So whatever their lifestyle was, all the things based on their age, contributing all to that moment. If they already have plaque, they're more likely to get more plaque.

That's correct. But A-O-B, and for that matter, LDL, did not, did not associate with plaque progression. And we already know from what we already published that it also didn't associate with what showed up in the baselines. We have yet in our data set to have an association between LACPRAP. L-Doh cholesterol and APOB with either plaque presentation or plaque progression. So if somebody came in and you have two people that are part of your study, both have the same super high APOB, maybe 180, let's just use that since you said that was the average, the person that already had plaque got more plaque progression in that year time snapshot.

And the person who didn't have any plaque that was there or had very little because everybody probably has some tiny amount of plaque. Correct. And we should unpack that a little bit because what we published before was called semi-quantitative analysis. So it's through human readers. The data we're publishing now is actually using AI guided reading, which gets really granular. And it's through a company called Clearly.

They do some just amazing analyses. Yeah, I had a clearly test done. It was fantastic. I really liked it. But they'll find plaque in every scan. Yeah. And there's nobody who's going to send their scans through that they won't find plaque.

unpack this because my sister, my older sister did it, and they literally said hers was zero, zero, zero, zero. Really? And so I'll send you the report. Maybe you could take a look at it, but like mine was like very close to zero, but I, I had multiple cardiologists tell me that it was the cleanest that they had seen in their practice for a guy that was my age. Now, mostly probably who's going to be doing these things? They're going to be people who are already thinking that they might have some plaque build up and stuff. But I'll send you both of those reports and you can take a look and let me know. But when my sister said it, I didn't get a chance to look at the report. I was like, like zero, zero, zero, like nothing.

Like I thought everybody had some amount of plaque that was there. And she was like, no, they said I had like zero. And it was just a clearly test. But anyways, we'll save that for another time. The bottom line is that everybody, no matter how healthy you are, and often typically, if you're above the age of what, like 10, you're going to have some amount of plaque that's there. It could be the tiniest little speck.

but they're going to find something that's there. So when you talk about people that plaque begets plaque, what was that threshold that people had a certain amount or certain areas where it was predictive that they were going to have more plaque on their one year long snapshot, right? So if everybody has plaque, what is the level of plaque that has to be there

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I don't know that I could actually speak to that specifically. as the funder, I'm technically blinded from data to the extent to where there might be some, as you're kind of, you're sort of suggesting there's a dotted line of sorts to where there might be plaque below a certain threshold for which there would not be an association. That's possible. It could be in a sub strata that could be found. But my understanding from Adrian, who isn't blinded but also wasn't part of the funding initiative, he's the biostatistician who's in charge of this.

and of course the first author of the paper, was that broadly correlative, it's just there. It's just that the lower the amount of plaque that you had at baseline, the less progression you would likely see moving forward. But again, then you've got whatever is going to come in the next year and the year after that and so on and so forth, right?

That's why I'm very interested in us doing a third set of scans. I'm currently in the process of raising money for us to do an extension. So I don't know if we'll be able to retain all 100% It may be like we lose a third. I don't know for sure yet. But that'll be an interesting question to get answered as well. So the people that are listening to this conversation, the first thing that they're sort of thinking is what does this mean?

Right? And I know that there's a lot that comes with that. But what can we start off with of what this means, what this doesn't mean, and what requires further research to unpack? What are your thoughts on that? First of all, I think for me personally, and I can only speak for me, I've wanted there to just be some data set for which. Because there was none. There wasn't.

There was no data set that looked prospectively at people with sky high levels of LDL cholesterol, but who didn't have some other independent variable of development of atherosclerosis. Okay. So for example, taking it back to Brown and Goldstein, I mentioned the little girl that they were looking at. the genetic disease that results in the high LDL is itself. This is homozygous familial hyperclostromymia. I know it's a big word, but super important illness because it has an impairment in lipid metabolism for why there's the higher LDL. But that same impairment also independently associates with greater risk.

So people have HOFH, which is rare, which is super rare. Very rare. We're not talking about people who have genetically predisposed to higher cholesterol or hyper absorbers. This is, again, a very rare disease. It's one in a million, actually. Yeah, the literally one in a million, by the way. If they have this disease, even with aggressive lipid management, the same level of LDL for somebody who has no genetic predisposition for it, and they already had this before we did our data, has a difference in risk.

Now, there's this other factor, the other factor, and this is, kind of why I brought up the lipid traffic jam, as it were. If you're metabolically unhealthy and you do have lower HDL and higher triglycerides, you will likely have moderately higher LDL as a result of having metabolic syndrome. I want to repeat that for extra emphasis. What's resulting in the lower HDL and the higher triglycerides also tends to result in the moderately higher levels of LDL. And then when you check out APOB, usually their APOB is off the charts, and they tend to be pattern B, like I mentioned before.

Why am I bringing this up? Because temporally, when you're becoming metabolically unhealthy and you get this lipid profile, that's a cluster, it's all these different things together. But then you become healthy and you manage to reverse that, all of the markers head in the other direction, including LDL. So LDL going down and associating with lower cardiovascular disease, risk for people at metabolic syndrome, it's confounded by the fact that the LDL is going down, I believe, as part of, for example, repair with the adipocytes.

You have less adipocyte hypertrophy, for example, right? And I think that's very relevant when you get back to the lipid trafficking. Okay, so in that case, how much can we be sure about the independent atherogenicity, the plaque-ca-causing value of LDL and APO-B. That's why we needed studies on people who are trafficking it, but not having the traffic jam to get a better sense of that. And that's why we needed this study, because now we could get it away from that cluster.

That's why, yes, for me, that's the big takeaway is finally we have population data and we need more. We need more population data. That's looking at metabolically healthy people with this variable of interest in and of itself. a chance to chat with one of your team members. Nick was on the podcast a couple days ago. This should be called, you know, Dave and Nick Week, right? We're talking to you guys.

We're writing about your paper. We're, you know, bringing up all the interesting points that you guys are making. From seeing everything, I'll tell you a few questions and thoughts that have brought up for me. And you can tell me whether or not there's any validity to them or if I've gotten something wrong. So is that okay? I'll share a few ideas with you. So one of the first ideas I had from this, you said it's right there in the title, that plaque begets plaque, is that you, your team, the way you guys think about this is that when it comes to the right diet for people, there's a lot of nuances. And even though there might be some people that feel really good on a low carb diet, the blanket

statement that, hey, you're not going to, you're going to be fine with the long term elderly. LDL that's super high, an APOB that's super high, that you wouldn't feel comfortable making that blanket statement in the way that like, let's say super hardcore carnivore types or keto types would say everybody across the board should eat this way and don't pay any attention to this idea that high LDL and high APOB is worrisome. You know, after just this partial snapshot, it's that one of the biggest things that's worthwhile for people to know is where do you stand currently? And that should be a big part of how you decide to undergo the right diet and your own personal threshold of where you feel your LDL or APOB

is in terms of your own comfortability and whether or not you want to treat it using maybe medicine or other means that might be there. So is that a fair way for me to be thinking about some of the way, like, I basically feel like you guys would have a much more nuanced approach and that you wouldn't just tell everybody that, hey, the ketogenic diet or this way of eating is right for every single person. My position still remains more in the realm of uncertainty than certainty. I realize we're in a space where people love to just throw out their, you know, the broad categorical claim.

You're fine if you're on X diet. You can ignore Y marker. right? And this includes LDL. Do I feel better with regard to my own high LDL in being metabolically healthy given these data? I do. Does that convert to not only do I feel certain that I'm fine, but I'm willing to go around to everybody else I know who's a lean mass hypersponder and say, you're fine. No.

It's not there. It's not there yet. In fact, I feel that we've just got to continue to build on the existing data that we have. Moreover, within the population. So we're talking population data. Within the population, there still may be a number of participants in our study who are on the further end of the outlier side that have plaque that actually want to take steps to do something about it. The thing is, I have the kind of freedom where I can just say that I'm mostly living in the unknown and then just be very cautious whenever somebody asked me on a should I question, which I'm sort of famously on Twitter saying, I don't answer the should I's or the will eyes or anything along those lines. I'm just trying to get the data and turn it around to you.

Now, second to that, can I identify a number of my friends? This includes Nick Norwitz and Adrian Sotomota. This includes Matthew Boodoff and people who work with like Brett Scher, that there's this emerging category for which they're looking at data like this. And as clinicians, they need to still have something they can say to their patients. Is there a consensus? There is. There's an emerging consensus that if you go on a ketamine.

genetic diet and your LDL cholesterol goes sky high, then an obvious next step to strongly consider is getting some imaging. If, for example, you get a CAC and your CAC is zero, that's actually some really strong data right there that at least in the immediate term, there doesn't seem to be much risk, almost everything, including data that precedes this study of ours, reinforces that. Again, this isn't medical advice. This is me just point to what they're saying. Conversely, any of those two qualifications aren't met, they would say, I'd feel more comfortable if you did something about your LDL or your APOB.

If you're not metabolically healthy and or if you have some existing disease that puts you to medium or high risk, maybe you should consider taking steps to do something about that. Again, this is not my opinion, but I'm comfortable repeating what they're saying just to at least have this discussion take place. It's so amazing that we have access to the imaging that's available today and companies like clearly, you know, no affiliation with them. Because for a long time, the approach and the advice for, let's say, my dad, you know, my dad has been on a statin for probably like 30 years of his life, right?

He's 75 right now, maybe longer than 30 years. And the approach previously was you run the basic blood work. and okay, your total cholesterol is high and your LDLSI, no real questions asked beyond that, we're going to put you on a statin that's there. And there wasn't even anybody at the time telling him to get a CT scan because I think he was still like in his 30s. And they were like, oh, no, you don't need that right now,

but we're going to put you on medication, you know, for the rest of your life. That's fine. Much later on after, you know, I think it was in his 50s, I think he might have gotten his first CT scan. And there's some information about calcified plaque in there. There's no information about soft plaque inside of there. And correct me if I'm wrong, but soft plaque is a major contributor. There's people that can get a CT scan.

Their score is not crazy high, but it's still a little bit high where there people are feeling like, okay, you need to pay attention to this. But underlining, they could have a lot. more problems with soft plaque that could increase their risk, but because they don't have imaging, they don't know. Is that a thing? I've heard that before. Yeah, you said CT scan, but I think specifically you met CAC. Yeah, CIC. Yeah, so in a, which is a CT, but it just, if we're being specific, the Agatston score is what you're talking about. Right, right. It's true that if you get a CAC, it's not picking up soft plaque and it's possible that the soft plaque could be more of a problem

than you realize. That said, I will tell you, I've become so much more bullish on CAC in recent years because of certain studies like the study out of Denmark that was phenomenal. They had 23,000 patients between two set points of years. And these were symptomatic patients. It's part of why they got a CTI angiogram,

for which you could see how correlative the CAC was with the CCTA. Right? that actually calcified plaque is a pretty strong indicator of your real risk level, right? Now, that said, gold standard 100% should be a CT angiogram. But I want to say, and I may be wrong in this, but I'm pretty sure I'm right. A good example that they had in that paper that I read was there was only one of those people who had a CAC of zero. There was only one in 250 that had at least one occlusion of 50% or more of soft plaque. So in other words, the level of disease of soft plaque being extremely high, surprisingly,

in spite of a CAC being zero, was super low. So without question, if it's a family member of mine and I'm concerned legitimately, I'm probably going to ask for them to do a CT angiogram. But the catch is that they do, they're definitely a lot more expensive. than CAC. And there is the potential risk of contrast eye, you know, beyond the higher radiation. Contrast eye is very low as far as having one of the complications. I think it's like 1 in 10,000 is that there might be something with the kidneys that

last a little bit longer. But for those folks who are like, well, I just don't want to get a scan, at least a CAC makes a little bit easier because it's cheaper, it's available more places. And it's at least a, you know, a fairly straightforward prescreen. So generally speaking, a CAC, which again, in most places you can get for like 90 bucks, 100 bucks, right? Is going to give you a good idea of not only calcified plaque, but that calcified plaque for most people is going to be very correlative to soft plaque that's there. So for the average person that's out there who's working with limited funds, you know, just get your CAC done so that you can get some sense. Now, help us understand, based on the scores that come back from that, what is,

you know, really bad, bad, okay, normal. Again, normal means so many different things based on an unhealthy population. And then, of course, what is optimal or where would you like to see people? And then reference that towards the fact of, you know, most people really start paying attention to a lot of this around the age of 40. And I've heard that most people, their doctor will tell them, especially for men who have a higher risk than women, or usually when you turn 40, hey, let's go get that CAC done. So help us understand the scores and the report that come back from that in the context of this audience here that wants to be healthy. Generally, at a population level, it's very rare for somebody and say their 20s or 30s to have a positive CAC. That said, it's not so

rare that somebody may not want to think about it again if they have some reason to care. Nothing, this is the thing I never feel like I can say enough. Nothing beats the predictive power of the existing presence of disease. You just, you can't come anywhere close to that. So if you have reason to think, especially if you've got a very severe family history of heart disease, that you may have some existing disease, you may even want to consider it, say, in your 30s. Now, us men, we tend to get the heart disease a bit earlier than women, so we tend to have at a population level, the majority of men having a positive CAC, I believe starts like late 40s to early 50s.

For me and my family, again, not medical advice, I'd like to see a CAC at least by 40. And just to see if it's a zero. A zero is a good number because it usually means given present data, even for those. people who have concerns that you probably won't need to take another one for another five years. And let me give actually a radiation dosage comparison. It's about one and a half times that of a mammogram. So it's really low. So I want to say it's 0.6 milliseconds.

And it may have even come down further on newer machines. Now, into the 50s, both men and women, that's where the population average tends to head tour, it's a positive CAC. I can't speak as much to what the ranges are, but if you do have a positive CAC, usually if it's 1 to 99 before crossing over 100, you want to look at what your own population average is for the age to get a sense of where you stand. Are you in like the bottom 25% or, et cetera? Now, there are a lot of people on the cardiology side that would say, look, any positive

score you need to now start treating like it's, you know, secondary prevention. But you may want to read up on a CACR who is really into CACs published a lot on this, and he has some interesting breakdowns that clinicians make use of as well. Where it gets interesting is you're talking about what levels of concern you should have at what stages. For folks who are, let's say, in their 70s or even 80s, my parents, for example, are in their 70s. I have the expectation they're going to have positive CAC scores. I wouldn't be surprised in late 70s if it's above 100. And then you kind of have to start working with what you're going to be doing about it and what they're willing to do.

I don't know about your parents, but my parents have, they're already working through a lot on the healthcare side of things. And so there's a degree with which I'm trying to at least get enough detection to know just how close the issue is to best figure out what care decisions they'll accept, right? Yeah. that we can do. Yeah, there's only so many things that people can do, especially at that age, there's quality of life. And it's definitely like a personalized program

for every single person that's there. But can we use this exact opportunity to bring it back to metabolic health? Yeah. I've told them this many times over. I've said that the biggest thing is, I want you walking, I want you to try to lift stuff here and there.

Staying strong to me matters the most as well as getting some cardio, staying up and about, keeping your metabolic health available is going to help your health span go longer, and it's a huge cardiovascular disease risk to let it go, specifically cardiovascular disease risk. And there's plenty of good data on that, especially as you get older.

Your return on investment just gets better and better for the time you put in as long as you can keep them in that mindset. Let's zoom out for a second, and we're going to be picking up on this thread, so everybody just hang tight. What creates plaque in the first place? Why do some people have plaque and some people don't have plaque? A hotly debated topic, there are two broad hypotheses that were coming up through all of last century.

One is called the response to retention. The response to retention is that our arteries have cells called endothelial. cells that line the vessel walls. And in time, a concentration gradient, if you will, of all of these particles like LDL particles eventually passively push their way in to our arterial wall. And then they start to develop plaques. Macrophages, which are immune cells, they're kind of like Pac-Men, they come over. They're trying to swallow them up because they're supposed to clear out debris, but they get

stuck. They get stuck. They eventually can die. Other macrophages can come. and they produce something called a foam cell, right? Now, that one hypothesis, the response to retention, suggests that it could happen everywhere, just through the process of how high those LDL levels are.

There's this other one called the response to injury, which suggests that actually it's the injury to the endothelium that results in the plaques that we're seeing. Now, this one's been mainly confirmed. In fact, we prove it in animal models all the time. we do things like denude their carotid arteries and that can actually create plaques that we can then study past that point. But the response to retention is, to be fair, is not mutually exclusive. It could be that both are true.

However, all concede very early on. I had a lot of trouble with the response to retention as stated because I would have expected more of a Gaussian distribution across all of the arteries. and where it accumulates the most is in places of greater sheer stress, bifurcations, places for which you'd expect more mechanical deposition through potentially damage. Yeah, like a fork in the heart where you have one thing going one way, another thing going another way, and you're saying that that just bifurcation, the split in the artery, is a common place where plaque would build up.

And definitely lots of coronary arteries where there's a lot of, pressure. It's important to remember even though we, it can never be reminded enough, the heart isn't just a muscle that's pumping our blood. It's conforming in shape on a constant basis. So those arteries are moving a lot. So try to imagine if you're an immune cell trying to do repair and the whole landscape is shifting around. To me, it just always made sense that that's got to be a more challenging space to operate things like ephrosytosis, which is the process of like tissue repair. And so I am not surprised that where there would be lots of vulnerability for things like the response to injury, that that would make sense. For me, I do think things like blood pressure,

I think things like hyperinsulinemia being relevant toward this development of atherosclerosis makes sense above and beyond the APOB containing lipoproteins like LDL. But I will be, and I'll emphasize this, again, I do think that in both cases, APOB containing lipoproteins like LDL are part of the causal pathway of atherosclerosis. So the development of plaque itself, 100% agree that if you look into those foam cells, you're going to find APOB containing lipoproteins and you're going to find macrophages that are dying there and so forth. But to say that they are the central drivers, that they are,

driving atherosclerosis, I always felt that there had to be more to the story. And really, this paper, these data are maybe some of the strongest I'm aware of because of the sheer magnitude of our participants' levels. It would be one thing if our participants were, say, an LDL of 160 and, you know, APOB of 100. But no, no, APOB of 180. And an LDL, I think our average is 255, something in the neighborhood. that's in the top 1%, actually the top 10% of the top 1% of the regular population.

We should 100% have seen a signal if this was driven by the response to retention, hypothesis predominantly. You had this year in between the snapshot. You have people that are already having high LDL, high APOB. If the traditional theory and idea of it's all cholesterol, it's all LDL, it's all APOB, was true, what you're saying is you should have seen across the board plaque progression, because especially things are exponential for how high the LDL and APOB was. And you guys didn't see that.

Right. That's basically what I'm hearing, right? Or at a minimum that there would be a correlation. Correlation. So at a population level, there was a plaque increase. But that was fully expected because that's going to be any 100 people. You could randomly grab the healthiest 100 people anywhere. And at a population level, especially if they're middle age, you're going to see a plaque progression.

The bigger question was inside that group of 100 would we see even a little bit of an association between how high their LDL and APOB was? Because again, we had not only an average that was very high, but we had a lot of heterogeneity between just how high it could get. Some folks were right there at the 190, 200 that was just right at the edge of the eligibility. but you had some people that were 400 LDL. I mean, wouldn't we universally expect to see that they would at least be at an average those 400s above those folks that are at the 190s?

I mean, per Brown and Goldstein, yeah, that would be the expectation. Yeah, and you guys didn't see that. Coming back to the topic of plaque in the different theories of why plaque builds up in the first place, in one of the theories you were talking about the role that injury plays, What is injury and what's an example of that for a person that would be coming into your study who already has some baseline level of plaque? Well, first and foremost, injury is just part of the game. Your vascular, it's already well known, is on a constant state of injury and repair. Like that's just what happens.

It'd be the same thing as if we pulled everybody on this block to find out who, has like never had a scratch applied to them, who is completely scar-free, even at the smallest levels. It's just, it's not going to be the case, right? So there's, of course, the natural process known as apoptosis. How can an endothelial cell that's literally the barrier between the blood wall and your subintimal space, how can it kill itself properly so that it can be replaced with another endothelial cell?

Well, that's a process. and that does involve a site of inflammation. It might be very tiny, but that does involve immune cells. It's just baked into the overall playbook, right? So some injury is to be expected, just in the same way that you would expect the roads outside this studio would undergo repair from time to time. So there's a process known as hemostasis,

which is if there is a, tear that's opened. Primary hemostasis is like a platelet plug. It can just kind of easily cover that injury. It's very simple. But secondary hemostasis is if the, is if the tear is like larger. And that actually involves a clotting cascade. It's way more complex and so forth. So I posit that somewhere between something in that neighborhood that we can already study, it's relatively innocuous, the repair happens relatively easily, to this other end of the spectrum, which is fully calcified atheroma, between. Between there, I think, is a range.

And I believe that there's a lot that happens. There's a lot of plaques that form that are in the same way, just like we'd have an injury on the outside. Repair just fine. It's just that it's not easy to study and measure. But have we seen people who, given certain, you know, protocols ultimately appear to reduce their plaque burden on net? Sure.

the catch is that usually that's something they're very proactive about taking care of. And there are a lot of things that are involved. But we still have to get more science on that. I just think that the injury itself, to get to your larger question, what can cause these injuries? I think that's actually a large list. A lot of things that can be introduced in the blood that as much as we're trying to control the filtration of coming in, we know there's things like gut permeability. and therefore pathogens can come in.

There's also ways in which it can be infarcted by not just things mechanical, but things, for example, like bacteria, so forth. But I think it's worth reemphasizing some amount of this is just to be expected. I think the story of atherosclerosis is less about those initial injuries. I think it's more about the inhibition of repair. the failure of our immune response from taking care of those potholes that eventually become bridge collapses, right? That, I think, is a more interesting question. So if you are hyper-insulin immune immune, if you are eating around the clock, are you out-competing your immune response?

I think you are. I think things like going on a binge are actually potentially deadly. But you may not know it today or this weekend when your buddy came into town and wanted you to do shots all week and then eat pizza all night and so forth. But you might have created a lot of turbulence that ultimately opened up a wound you can't feel in your LAD that seven months later or seven years later becomes your next heart attack. You know, you mentioned that on our first podcast together, but it really clicked for me this time. So it's not just injury, which again, it could be bacteria exposed to other stuff, whatever. But part of that also includes, like, a lot of drinking when you were young, smoking that somebody does. It could include being exposed to an environmental

job where you're exposed to more toxins, microplastics. We know that those are sometimes found inside of, you know, plaque that's there. So a lot of different things, some that you just will have as part of normal living, but some that can come through increased exposure through lifestyle. Those all can play a role in injury, but you're saying that, yeah, okay, that's all there, especially if you move away from, you know, the bigger ones, like we know smoking, et cetera, if you're not smoking as part of your diet. But another question that we really should be asking, and there's not enough focus on, is why doesn't your body have the normal capability to repair those sites?

what is impacting immune function? So the same things that injured in the first place, if I'm understanding correctly, those things that could cause repeated injury. For example, if you are regularly drinking to a degree that is excessive drinking, you are going to be somebody that's going to constantly be injuring yourself and prevent and distract your immune system. If you're somebody that's dealing with another immune issue that's taking up your bodies, like I'm guessing, like if you're dealing with an autoimmune condition where your body is kind of

distracted a little bit, could that be an example of something that could also prevent potentially the repair from happening? Potentially. But I use this analogy a lot. I don't know if I did this on the last podcast with us, but think of breaking your leg and then think of not knowing that you broke your leg, but you keep walking around on the broken leg. So you make the injury more and more complex and more and more difficult to repair.

when you finally end up going to the hospital, right? I do believe that the nature of how the injury occurs may be unpredictable. It may be that the weekend of binging didn't create a problem. But it could be the marathon you ran the weekend after, did. And then you're not taking enough time to recover on it actually is what did in that tear that made it worse and worse and worse. you said, I feel great. I'm going to actually do 10 more morning runs. In fact, I'm going to prove this to my wife.

She says I don't, you know, I'm always too, too broken down to be able to do repeat runs. And I'm going to prove her wrong. So I'm going to do 10 mile runs for the next five days on a bet, right? This is why I think, by the way, a lot of extreme athletes have ridiculous CACs. They have huge CAC scores. And they go, I don't understand why. I'm as healthy as an ox.

I'm doing everything right. And then my first question whenever I have a friend that tells me this is I go, do you recover though? Do you really take time to rest off those injuries? Because I believe that there are internal injuries that, again, you can't feel. You cannot feel there's not nerve endings to every endothelial cell. And we don't have imaging right now that is so good that could pick that up. Which would be great.

Like, if you could wear some device that's actually monitoring the composition of your coronary arteries so they could actually pick up when something like this happen, I'll bet it would change the whole landscape. But as you know, from her study, just getting a CT angiogram is a bit of a production. What's that other thing that a lot of runners end up getting artythmias? Talking about aphib? Yeah, AFIB. Yeah. Right? A lot of runners, is that connected at all with this too?

This is a little outside of my wheelhouse, but as you know, the heart's very electrical. It's based on a sinking cascade, right? And so I have always been kind of curious how much of that comes back to electrolyte usage. I've certainly ran into not getting enough electrolytes when I was doing running initially that I needed to have way more salt than I was giving myself credit for. When you were a runner? When I was a runner, yeah. Yeah.

So pulling back to this concept is that we have injury that's going to, to come from a natural part of living, but there are things that, is it a fair statement to say that living a life that minimizes things that are known potential injury is going to be supportive, right? You can't completely remove injury to your heart, but staying away from smoking, you know, drinking too much with the definition of that has changed a bunch. A lot of people now say that's maybe more than like two drinks a week, right, can be potentially be, impacting. I don't pretty much drink at all, but also reducing your exposure to excessive levels of plastic. Is it fair to say that those things all are good things for your overall health

and potentially could be reducing your risk of injury? Is that a fair way to look at it? It is, but here's what I'm going to bring you back to my original unknownest philosophy. That's how I like to call myself is I live more in a world of uncertainty than other people are comfortable with. I'd be willing to bet we know maybe 5% of those things such that we can prescriptively try to avoid them. And it turns out there's another 95% of things we have yet to discover are injurious. I do feel more confident in what it is we can do that inhibits the immune response and not do that. Okay, let's talk about that. Okay.

What are the known things that inhibit the immune response? So we're talking about the body's ability when it gets these, injuries to go in and repair, to replace out the dead cells and the endothelium that maybe have gotten damaged, and whatever version of that, that is all the specifics that is way over my head. So what impairs that process? Insulin is one of them. Insulin. Okay, great. Let's start there. So there's a, there's, and I wish I had the paper in front of me, but there's a threshold of insulin that at above a certain level is going to put your immune response and more of a pro-inflammatory state then.

And this actually kind of comes back to how it's an anabolic hormone, right? So there's a lot of great research that's on this for my colleague, Chavon Huggins, who was really looking into this way back, I want to say like seven, eight years ago. And it was fascinating because she was putting a lot of these papers in front of me that indeed showed this like delicate balance the immune system kind of counts on in what I like to call the closing hours, which is when you're sleeping, right? When you're, when you're no longer eating and before you're entering your circadian rhythm, that's when a lot of

the best immune work happens. So when you're suddenly feeling like you need to rest, you need to be laid up, I think you need to follow that instinct, right? When you're, when you're sacked out, you're tired, I'll bet you that it's a huge cardiovascular disease risk when you're enforcing greater consciousness, especially if you're eating during that time. The one piece of health advice that almost everybody knows all say that I feel like I could stand on is not to eat, say, three to four hours before you go to sleep. It's the one thing I try to hold the tightest too because I want those closing hours for my immune response.

And that way I can also ensure the insulin levels are lower. That way I can ensure hopefully there's no engagement by my GI tract from food that's still working its way through digestion. You know, GLP 1 agonists get a lot of discussion with regard to medication, but the first time I was learning about GLP 1 is that how food in the hindgut can have an impact on stimulation with insulin, for example, right? Okay, I want all of that off the table so that I can maximize my recovery potential to leave that available for my immune response.

Now, the thing that I also speculate is sometimes that may not be needed, could be even most the time that may not be needed to be completely on target. But it's needed enough, I believe, as evidenced by those people who seem to be out competing their immune response from those two extremes. People are not only metabolically unhealthy, but I mean, those folks that are waking up in the middle of the night hungry and eating, they're usually near the void, frankly. It's very, if you're somebody who's in a place where you feel like you have to eat around the clock, the data does not look good for you.

But on the other end of the spectrum are these massive over-exercisers. They're getting such an endorphin rush. And the runner's high, which I've never experienced, by the way, I still feel like it's a hazing ritual. Those people who I've met some, I've met ultramarathoners who just cannot go one day. They can't go one day without running many multiples of miles. and often, often they have severe heart disease. So you've got to prioritize recovery. So one major action item for everybody is really prioritizing, not eating in that three-hour window before bed.

Do you think that there is potential benefit to moving that window up even earlier? Again, in the unknown, but your theory? Yeah, potentially. Because we have this sort of thing where in most cultures around the world, especially if you look at like the Indian community that historically in the Hindu or Jain tradition or Buddhist traditions where fasting was a huge part of their culture like other religions that were out there, it was always that I would see the emphasis being on skipping dinner. You know, nobody would really skip breakfast.

They would skip dinner. And now because of our society and the way that things are and us being social, sort of fasting in our modern context, especially here in America, when it got. got really trendy was people saying, okay, I'm going to skip breakfast because it's a lot easier and then I'm going to eat dinner. I've always felt better and I feel like I get the benefits when I have an earlier dinner and I actually feel like my brain turns on in the morning when I eat and I know everybody's a little bit different. That's a lot to be said, but potentially you could get some additional benefit if you had even a longer window of not eating before bed. I eat two meals a day,

one at 10 a.m., one at 5 p.m., unless travel kind of throws that off, but that's generally the pattern I shoot for. And it's not because I'm just obsessively into intermittent fasting or anything on those lines. I care the most about that window before going to sleep. So it's rather than trying to fit it within a certain meal time range or something, I allow for I can eat as early as I want to. I don't mind that aspect of it. I just, to your point, I like eating at five because, if I'm up to 9 p.m. 10 p.m. Even if I start to think about it, I find that I have better control, self-control, and recognition that I'm just wanting to do it because I'm bored.

Because enough time has passed where I'm starting to think about food, not because I'm genuinely hungry for it, but because it's bored of eating. And I feel like that's just a Western society phenomenon, only because we often have things like lunch breaks where we start getting aligned to, when does this fit into my schedule? When does this, you know, makes sense from a time allotment standpoint?

But to your point, I personally think our ancestors were almost always exclusively eating during the day, oftentimes competing with each other for like, you know, the hunt comes back and the meats finally cooked and everybody's trying to get. get their take and probably eating it as quickly as they could, right? Even where food starts to get towards where it's being preserved, there's a lot of ritual, even to this day, in a lot of societies, around the food and not to treat it like we kind of do here in the U.S. Yeah.

It's kind of like something you're going to eat off your lap and your car while you're on a Zoom, you know, with some other coast trying to get something done. and it's just an afterthought. It's one thing, by the way, I liked when traveling to Europe especially is they're in Europe. Their meals tend to stretch out over a while. They tend to be smaller portions. And I think that that's a lot healthier.

They also, by the way, the restaurants close much earlier than ours. Depends where, like sometimes in Spain and like people will eat super late. And some of that influence that ended up in like Argentina, like I'll go to a restaurant, When I went to Argentina with my wife, people are barely getting to the restaurant at like 10 p.m. Sometimes. It's nuts. I've not. They eat so later for there.

That's Argentina specifically, which is obviously not in Europe. But yeah, it's interesting. It's interesting depending on where you go. Sometimes I feel like that's one habit. That's not the best habit that they've inherited. So you were going down along the lines of things that we know that don't impair our body's natural ability to repair itself. Right. So one of the first ones you mentioned was not eating too close to bedtime, keeping that sort of three-hour window. If you can make it four, amazing, especially, you know, you're going to sleep at 10. You're eating at five. So, you know, you probably finish your dinner at six is my guess, right? Yeah, pretty much. Yeah. Six. So you have usually five-thirty. So you have six to seven, seven to eight to nine, nine to ten. So you have four hours there in that window. What else is another takeaway of something that doesn't impede our body's natural immune repair?

process, especially when it comes to repairing the heart? Well, certainly, and again, I should qualify. I don't know how much of this applies to the heart specifically because it depends on whether or not there's a backlog there to take care of, right? So existing heart disease, here's some things that I'll just stay up front, I think, are very plausible, easy things to infer. There is a rate limitation. There has to be for virtually any bodily process, given that you can only make so many

immune cells. You can only have so many of them active at a given time. And therefore, another thing that I'm mindful of is rate limitation just by sheer quantity. So if you're already battling a huge inflammatory response, there's a lot of data that backs this up as well. You're at a higher risk of heart disease. I think a good piece of that is that there's a rate limitation. The very same macrophages I'm talking about, they come from monocytes that differentiate into macrophages. Macrophages, by the way, are one of my favorite cells of the body. They're amazing.

They're incredible. But can you have unlimited monocytes, you know, in production and in constant? There's some limitation. I don't know where that stands. But I think if you've got systemic inflammation from multiple other processes, it's a backlog problem. There's going to be only so much that it can attend to at a given time, right? But then there's also, as I mentioned earlier, the complexity of the injuries themselves.

So if I've got complex injuries elsewhere in the body, let's say I have severe burns. It's another great example of something that can often associate with greater risk for heart attack. I think it's quite possible that there's a degree of occupation by my present immune response that is now in competition with what might be happening elsewhere in the body, particularly with regard to repair. in the coronary arteries. Again, I always want to be careful to emphasize these are hypotheses, but I think that we have a lot of data in hand that definitely substantiates how much the immune response relates back to exactly what we can do about atherosclerosis

and hopefully remove those barriers as much as possible. And one of those, I think, is watching those inflammatory markers in your blood work to at least confirm or disconfirm if there is, something of a systemic inflammation elsewhere. CRP interleukin 6, what else was you put in that category of these inflammatory markers? I like glycate a lot. Glycate is really great. A ferretin could be considered a, I mean, it can also relate back to iron, but I like it also

as an inflammatory marker. A lot of the interleukins are great because they can also give you greater specificity. Another good one is TNF alpha. And yeah, myself, I really like CERLU. reactive protein. It's a very high sensitivity, non-specific inflammatory marker. So it's not great in in regard to diagnosing something of specificity. But let's say your CRP comes in and under one, pretty decent chance you don't have something

inflammatory going on. A lot of the advice I give people when they're dealing with, for example, something that is, they understand to be autoimmune is I say, you may want. want to consider getting a C-reactive protein test at least to determine if this is related back to inflammation. Because if there is an immune response in play, that at least tells you one large category of things to then investigate in over here with regard to that immune response. And that means that the body's aware of it.

And that means that the body is implementing a plan to attack it and deal with it. And that gives you a direction to go. Or it doesn't. You're experiencing these symptoms, but there doesn't seem to be inflammation related to at least not as at a systemic level. That's also useful. There's been individuals that have been on this podcast that have been maybe dismissive or critical of even the idea of lean mass hyper responder, right?

I don't need to not name names because I think it would be helpful because you guys have had different sorts of discussions on Twitter, sometimes not discussions, people just tweeting about it. But like I'll take a couple people, for example, like Simon Hill's been on this podcast. He shared his understanding of what he thinks about things. this was a while ago. This was on during COVID. I was telling him that I fall into that category and, you know, he had a very, he had a very large smirk on his face and then shared his perspective on things, which I appreciate, by the way, I want everybody to share their perspective on things, even if they

disagree with me, because I'm not an expert in any of these categories and my audience wants to learn along the way, just like I do. Then you have individuals like Lane Norton, who's had a little bit of not, I guess like you guys have asked him for dialogue, but maybe he hasn't participated in the dialogue with you guys, but has made comments about what his thoughts are about, you know, how problematic it is to have high LDL, high APOB over the lifetime and where that fits into the studies. When you take any of those individuals that I mentioned or anybody else that's been a critic of sort of the lean mass hyper responder movement in general, what do you suspect the response is going to be to the publication of this study? I know I've watched in real time.

as these, gosh, I want to, I don't want to poison the well, as it were. Because I do want to, both the gentlemen that you mentioned, I've had many great discussions with in private and to some degree in public. For example, with Simon Hill, I've been on his podcast. And I've had discussions with Lane Norton, both in private and also at low carb Denver, not too long ago. I would love to have the kind of conversation you and I are having now with them after the publication. What I think the response will be, because this seems to be where the new position has moved, is, well, this is a tiny group of people. So it used to be, well, there's too much of a setup that these folks are metabolically healthy, and therefore that's in its own way putting thumb on the scale. I welcome that change in that that's not what the position was when first talking about lean mass

hypers because there was a sense of, well, it doesn't matter if they're metabolically healthy. There's still going to be at high risk for having a high LDL APOB. That's what most of the critics of our research were originally stating. As more and more of these data had been released, and I think because a lot of even the cardiologists have more of a patient pool that includes lean mass hypersponders, I think there's been a broader recognition that maybe they're not at a population level at high risk, such that that's kind of being quietly conceded, right? I don't want to put words in their mouth, but that's how it seems to where now the new

statement is this lean mass hypersmartre research is not that interesting because this only relates to this tiny fraction of people. Now, if that's the case, if that's where sort of the new position is, I don't mind that. in regard to a lot of people that are featured in our movie, a cholesterol code movie, as you know, is going to be coming out soon, is not folks who are using the ketogenic diet for weight loss. They're actually using it for efficacious reasons. You mentioned bipolar earlier, right?

Nick Norowitz himself has been using it for his all sort of colitis, a schizoaffective disorder with Lauren Kennedy, for example, right? There's metabolic mind I'm sure you're familiar with. all sorts of great research and a lot of new videos and so forth. There is an important distinction we need to make for people who are finding a big solution with the ketogenic diet, but the one thing they're afraid of is the one thing I was afraid of 10 years ago when I saw it. They just want to know is the risk level there at a population level.

And if folks like Simon Hill and Lane Norton are willing to acknowledge, okay, but they're part of a tiny fraction, that's a big jump right there. Because quite literally up until now, it's just been a broader sense of no. The existing data that we have on the disease populations informs us for the healthy populations so that we can make this claim that, no, doesn't matter what your circumstances are. You have high LDL, you're at high risk. End of discussion.

Because the fear would be for some of those people that this is life changing for. For example, we had on a woman named Hannah Warren, I believe was her last name. Oh, yeah. Type 1 diabetic, right? No, she. Maybe I'm thinking of the wrong one. She works at Metabolic Mind, the organization now, and she's part of her, like, press team. And she came on the podcast just when she had joined the team.

And she has her own journey of being diagnosed with schizoaffective disorder and how she went on ketogenic diet, vegetarian ketogenic diet. to that end and had a complete reversal of her symptoms, basically by seeing the work of Chris Palmer. And so what I was saying is that there's people like that that have been on this podcast and is the fear that with a lot of these leaders in this space saying, look, you're going to die early. There's no reason you should be on that, that you would end up trying to protect your heart later on based on the theories of public medicine, but in reality, or but the tradeoff would be right now you're being impacted by this mental health disorder, bipolar disorder, schizophrenia,

or ulcerative colitis in the case of Nick. And so some people might be so afraid of dying in the future that they abandon this therapeutic diet that's actually working for them right now. Right. I'm sorry. It's an answer they deserve. And I'm appreciative of everybody who's helped to contribute to make this thing happen because, you know, while I obviously have helped the spearhead get this thing going, this is as grassroots as it gets. I'm so thankful for Nick Norwoods and Adrian Sotomoda for every step of the journey and helping to make this happen for Matt Boodoff, but particularly for all these people who've contributed, literally, you know, reached into their pocket, gave us the money to make this science happen that should have already been happening. There should be not only the

interest in looking at whether or not this level of LDL will associate in these folks that are metabolically healthy, but specifically for people like you're talking about who are using kugenic diet for therapy, not just as another way to look. Most people who are type 2 diabetic and I will sound not like a low carbure right now, I would say they have lots of options. They have lots of options to try to take care of it. But virtually all the options are going to be, to quote Ben Bickman, virtually all of these options are going to be some low insulin version. Right. So if you can calorie restrict and you can find that's just something you like more than say low carb, that's fine. But for some people, ketogenic diet is the one and only thing that they've been

able to find that helps them with their medical condition. That's why one of the reasons majorly why this work is so important. One of the things that I took away from the study that was there for me, from at least your explanation of it, Nick's explanation of it, is that I have a couple of my close guy friends that are above the age of 40 and kind of abuse their body growing up through different sorts of means. One would be actually going on a high-carb sort of Indian vegetarian diet, not having a lot of dedication to physical activity, not really having resistance training being part of their repertoire, so being a little bit under-muscled. And, you know, we're probably drinking like a lot of their peers that were there, and that kind of

continued into their behavior of trying to keep those college years alive, even though they're well beyond, you know, college. And they wake up around 40, and they're like, I really want to focus on improving my health. And there would be many years ago where I might have pointed them towards resources, which would just be, hey, great, do all the basics that we know, cut down the drinking, you know, most of them are not smoking. That's great. But dietary-wise, you know, start moving in a direction of low-car, maybe get a glucose monitor in some instances, and, you know, try to get a lot of these good quality fats, proteins in your diet and, you know, continue to improve in there.

If you can get some blood work done, get some blood work done, you know, let's try to improve those lipids that are usually in the wrong direction. Let's get control of the inflammation. Let's find you a good practitioner that's out there that would help them. And I still believe in all those things. And the one element to go back to something that you said is that I be, especially if that person is going to lean more towards low-carb, higher fat inside of their diet, I would really want to push them towards getting some sense of imaging,

which a few of them have gotten on their own, done clearly scans. And in some cases, have come back with a pretty significant amount for the age of 40, 42, 43. They've come back with a significant amount of hard and soft plaque that's been there. And that has informed them. I'm very lucky my brother-in-law is a cardiologist. that's very hip to this world, very open-minded, you know, has his background in functional medicine and would tell them that, hey, listen, you know, this is how to understand your blood work,

your own risk. In your instance, especially where a lot of these guys are South Asian, Indian, where there is cardiovascular disease running in the family that's there, there's been a much higher emphasis on, hey, yes, do all these other things. and yes, get your fasting insulin in the optimum range, do all this stuff. And in some instances, you might want to be a little bit more aggressive with certain therapeutics. That could be everything from azetamide on the low end or in some instances maybe something

more aggressive because you're already coming into this scenario with some level of significant amount of plaque coming from your lifestyle previously. That's kind of how I've seen it. Now, I'm not a medical doctor. treating these people. I'm just sort of pointing them in the right direction and ushering them to people who to talk to. Do you think that's a fair way for me to look at things? And as always, you know a lot more of the specifics. So what are some of the holes and nuances that I'm not covering? Well, of course, I've got to reassert my answer to your question shouldn't be taken as here's

my advice to you to give his advice, right? Yeah. I will say here are the two broader school of thoughts. One is the statins are the way and it doesn't actually matter why there's the change. Statins are just the best heart disease medicine. So if you have existing plaque, that's just the direction you should consider going. One of the more interesting things that I've seen change over time with regard to that school of thought is that it doesn't necessarily need to be maximal dose statin, typically 80 milligrams or 40 for some of the stronger ones. I think even, I don't want to put words in his mouth, but I think even Peter Rottia was suggesting you get, what is it, 85% of the benefit from like, say, 5 milligrams

or 5 milligram statin or something like that. And then there's another school of thought that is, well, whatever alters your LDL is because it's the major control. contributor, you could go ahead and use something like Inzotime, which is limits cholesterol absorption in the gut. And for what it's worth, in the lean mass hypersponder Facebook group that we have, many people would discuss strategies that they want to take on if they're not comfortable with their high LDL. Inzadamide is probably the single most popular intervention to bring down their LDL. I'm on a Zetamide. I've shared with my audience.

I think what is the initial dosage, like 10 milligrams or something like that? that, five milligram, something, I'll fact check that and put in the show notes. Even though Mike clearly came back as basically incredibly clean, and I'm always updating my knowledge, who knows, maybe I might rethink things through here, and the fact that a Zetamide is focused on cholesterol reabsorption, and that largely most people that I've talked to, including my brother-in-law, my cardiologist, Michael Twyman, is like, you're not really worried about, you know, side effects that we know know of. a very cheap drug.

I'm not even using insurance to purchase it because it was just a pain in the butt. I think it costs me like 60 bucks for like a 90 month supply or something like that. It's super, super cheap. I thought, okay, everybody's trying to make their decision for what they're comfortable with. I think I'm more comfortable taking this, especially because I'm one of those individuals where my APOB is 180. Now, to share with my audience, me having been on it now for almost about a year, my APOB, has not really gotten below 75, which is still a lot of people might consider high risks

that's there, right? So just sharing that. But I actually am comfortable personally, not medical advice to anybody else. I feel a lot more comfortable with my APOB at 75 when it comes to rolling the dice of what could the future look like. And that's just my situation. Listen, there's just so many people who are in this exact position where they're listening to multiple sides, which, by the way, I do encourage, listen to multiple sides who say, look, I feel mostly this way, but you know what, I'm going to kind of, in my mind, I'm going to be hedging my bets by going this other way, right? And to that extent, it's all your own personal health journey, right?

We, there's a, to be a good scientist for as exciting as these data are that landed, the five-year data could more substantiate the lipid hypothesis. It's possible, right? This is, you, to be truly open-minded, we've got to be able to say there are still other possibilities that we couldn't know until we have longer data to be able to substantiate it anyway. Could well be that there's a subset that we're not yet aware of, for which higher LDL will show that association and everybody outside the subset doesn't take.

exist in that fashion. You'd think I was pouring cold water on my own data by just saying these things. But no, this is just part of that living in the uncertainty and accepting it. You work from the data that you have, not just as a clinician, but as a patient, right? So it's not a bad thing to be able to say, here's where my comfort levels are. And here's what the data show. I just hope you can do both. I hope that you can have whoever you are. I hope you can get a good barometer for where your comfort levels are. And I hope you can care about getting enough data to make an informed decision for yourself with your doctor.

Do you feel that one of the thinking by, let's say, people like Peter Attia, who's been very vocal about his views and how they've changed and his book, Outlive, is part of the thinking from some of that group that, look, we have to do public medicine because the vast majority of people are not healthy. and so when we're talking about making these recommendations about getting LDL and APOB low, we're making them within the context of understanding that most people are not metabolically healthy right now and that, yes, diabetes is part of the four henchmen of the main killers that are out there, and he definitely wants people to, you know, get away from being diabetic or pre-diabetic and that sort of thing.

but that we're living in a world that people are not healthy, not metabolically healthy. So we have to make recommendations based on that. Is that part of what's driving a little bit of the view? I think there are a number. I'm not sure how much of this is embodied in Atia per se. I think he really does believe that APOB is, like if we give ApoB low enough, we just,

as I think he puts it in his book, that it'd just be an orphan disease, that, that, cardiovascular disease would effectively go away if we could find a way to just make it. So, for example, they're trying to develop means by which it's like CRISPR to give people PCSK9 loss of function. But here's where I may sound like I'm an ultra-LDL skeptic, or sorry, an ultra-LDL lowering skeptic.

As I said on Simon Hill's podcast, as I'll say here, I don't know that there's not a trade-off. in most things for which there's an intervention, probably arguably all things, there's a trade-off and you want to be sure that you're on the profit side as opposed to the lost side. I do know, and I should at least defend, that apobiliproproteins do serve purposes in the body, including LDL. For example, they buy into pathogens. They carry alpha tocopherol, which is an antioxidant.

I think they're also made use of, for example, for structural demand, which kind of gets into parts that we don't yet have published. in the Lippin Energy model. I don't think that it's consequence less taking steps to lower LDL doesn't mean that. I think it's necessarily on net a bad thing. But I think it's possible. And in that regard, I'm not going to start with that assumption that there's only benefit to be had.

Now, if you only had that opinion, then I could understand the advice because then you're casting a wide net, right? And even if it was benign to change your LDL levels for a lean mass hypersponder who's metabolically healthy, no worries, because the other 80, 90% of the rest of the populace that is unhealthy would potentially see benefit from their perspective and taking steps to lower their LDL. Possibly. That's all possible.

But I don't like that approach in general if that's kind of the thought. top process because what you're describing is, hey, we need to find guidelines that are going to apply to the majority out there, but lack nuance by design, right? Because if you're trying to, if you're trying to push forward nuance, you're asking questions, you're getting specifics so that you can say, here's the data that best applies to you that we have, as opposed to giving broad statements and saying, we're going to try to one size fits all. Because when you do something like that, you end up with these awkward positions where you treat all BMI as overweight if it's high.

And that's in most Americans who have high BMI are over fat as opposed to overmuscled. But there are some that are over muscle. Should they take the data that applies to BMI to apply to them universally? No, of course not. If you had to give a list of takeaways as a recap here of what at least we could infer or has strong sort of backing, maybe not directly from the study, but it sort of reemphasizes things that are known. For example, I mean, it's pretty obvious for everybody, but try not to get plaque built up in the first place. Is that one takeaway that's there? It's like being healthy as early as you can for the people that are growing up on podcasts and things like that.

Is that one takeaway that comes from this? I'm not even sure on this one, which may sound odd. I don't feel confident enough that we know the cycle of plaque progression and ultimately plaque cessation or even regression. To be able to know for sure, we don't have, we don't have good trajectory data. So in the same way that you might get a wound on your arm and for a moment while the clot is forming, it could look like it's terrible if you extrapolate from that, that it's just going to continue to build and build and build. I don't know.

I don't know if you went on a perfect diet on day zero, but you're one of these friends you described. You had terrible lifestyle before up to age 40. And then right then we knew the perfect protocol for you to go on diet-wise, all the right supplements, that's everything. That on day zero, plaque halts. I doubt that. We already do have some decent data that non-calcified plaque is going to be more likely to get calcified, and that's usually a good thing because it's getting more stabilized. Staten producers would say this as well, right? But how much of even soft plaque progression might turn out to have a net benefit under healthy conditions. I don't know that we can say. I don't know that we have a good answer for that.

I already take enough heat for just suggesting that that's a possibility. But so many things in the human body work that way. Again, getting back to embracing the uncertainty, I don't think that that's a bad thing. This is another reason why I want to get the third scans, not just so that we can treat this as one giant score that's either going up or it's going down, but I'd like to see three points along the way, just because I think we could get better at answering this exact question I'm putting forward to you. I think a better way of putting it is take it out of the shoulds. If you have plaque at baseline, can you expect there's probably more plaque in a year? I think we have pretty good data to suggest that yes, even if you're metabolically healthy

and you have plaque. At a population level, there seems to be some data suggesting you'll probably get more. How much more seems to correlate with how much you started with. Could one takeaway be that imaging is important. And if somebody has the means and is paying attention to this, how closely should they be following? They have some plaque that's there. They're worried about the progression. They might be having, they have high LDL, high APOB. How often typically have you heard people talk about making sure to get that snapshot with the tradeoffs of, you know, there's some radiation exposure? What have you seen that's out there? I think that's going to be a very individual choice. I can tell you what I know. Me personally, if my, if my.

Let's say I took a CAC today and I found out my CAC, bear in mind I'm 51. So my CAC would be, let's say it was 10. I'm probably getting another CAC in three years. I'm going to be frustrated because my CAC is zero. Last three times I checked. If my CAC is 500, I'm probably getting a CAC next year. Because I'm going to care a lot about the progression rate for that point. The same regard with the CT angiogram, if I found that my vessel disease was pretty average for my age, I might be interested in getting another CT angiogram in, say, four years or five years.

If it was extremely high, if I was like in the top 20% for my age, I might be getting it more frequently. The beauty of imaging is not only is it so predictive of future problems, but you can at least check into something. some degree as to whether or not you're making it worse much faster based on the things that you're doing. And the radiation level has now come down so much. CT angiogram used to be 10 times the radiation it is now. I mentioned the CAC is 0.6 milliseconds. CT angiogram for me at zero CAC was two millimeters, which would be five mammograms, right?

For reference, just a year of free living is 3.5 milliseconds, I believe. Do I feel like a takeaway that was already there for, I think, the last 10, 20, 30 years? That imaging tends to be extremely predictive, extremely prognostic towards future heart disease outcomes. Yes, we reinforce that even more. But one neat thing is that this is even within a healthy population. that imaging is important to get a sense of where your heart disease risk is at right now. Conversely, the takeaway of how much APOB and LDL will be predictive towards my existing or future plaque. It's pretty powerful population data we have that it's not, at least at this point in time, at these levels,

or the amount of time that they've been on a keogenic diet. So it feels like there's a takeaway for somebody like me, which is if you already don't have a lot of plaque, your levels look good. it should add, I'm saying it from my end. I know you don't like the word should, but it's, it could add to somebody like me or let's say, let's talk about myself. It adds a little bit of comfort to me where it's like, okay, cool. This is even more of a reason that I'm less worried personally about having an APOB around like 70, 75, an LDL because I already don't have plaque.

I am metabolically healthy. I'm going to continue to, you know, be committed to being metabolic healthy, continue to focus on lean muscle mass and all of the things that are there, not just diet, you know, I'm going to double down on reprioritizing and prioritizing recovery, right? That's something to give them more attention to. But that just the idea that if somebody brings up, well, how do you feel about that? What's your level of comfort? this would be one study in the body of work that's out there that would make, hey, well, you know, there's some questions about the traditional model.

And this is why I personally feel a little bit more comfortable having a little bit of a higher LDL than maybe mainstream medicine should say that I end up having. That's how I feel about it. Yeah, here's a good way of me putting it. Would I be surprised that there's going to be a lot of people in your exact context that will be reconsidering their decision? absolutely. I mean, certainly I'm being informed for myself based on our population data as to whether or not, as to what degree the risk is. Am I more comforted? I'm comfortable saying that. Yeah, I'm obviously more comforted as far as what that association is, especially for the time applied. Does that lead me to a place of complete certainty? No. And, you know, I'm not actually sure if I'll

ever get to that place. Like it's even with a lot more robust data. But is this the most, specific data by far that we've had in hand. Yes, that's where I think that there's a pretty substantial jump that we've made with this study. There's nothing anywhere close. And which is a shame because we're now raising money for a new study. I kind of hoped that we would just be one of 10, that these new data as they're coming out, especially when we were putting out the preliminary, that we'd have a lot more teams that

We're interested in studying lean mass hypersponders. But this is the hard truth. There's just there's not a business model to apply to it some way to, you know, you pretty much get money for research from one of two channels. You get it from the government, such as through the NIH, or you're going to be getting it through some device maker, you know, for diagnostics or some kind of product such as what you can do with these numbers, pharmaceuticals, something like that. This is the only way we can do it is through crowdfunding.

Well, I'm happy that at least you guys are doing it because if it wasn't you, it'd be zero. Talk a little about the movie and then talk about the research. There's going to be a whole campaign. We're going to link to it in the show notes to not only raise awareness about the study, but also have people who can join and be citizen scientist along with you. I'm excited. I want to contribute. Let's talk about the movie first, and then we'll talk about where people can go to support

the research. Yeah, it was super exciting. Jen Eisenhardt, who's made several other documentaries, including Fat Fiction, was the one she had done before this one. She and I got connected through Brett Scher. And quite literally within a matter of weeks from us connecting, I was going to be getting that first set of scan data shown to me by Dr. Budoff. So me as the funder, I don't get to see things until they,

come to wrap up points, right? And so I was going to be seeing a summary of what the data looked like, and it was the first time all 100 scans were being analyzed. And in the course of figuring out that this was going to happen right after meeting Jen Eisenhardt, we worked out, you know what, let's get the cameras in that room. Maybe we can turn this into a documentary, just actually follow the entire story end to end for the study itself, at least from when the pre-limbed data came in. So sure enough, that's when the cameras got there, you're literally capturing my reaction as it happens in real time. And eight days later, when I presented at low-carb Denver, they were there as well. Pretty much,

there's just multiple stops throughout all of the data getting shown to me. They're sort of the major through line of the documentary filmed over two years. But then on top of that, we did a whole bunch of interviews, which I mentioned a bit earlier. Nick's in there. Robin Dobbins is in there. There's an amazing story of a type 1 diabetic boy, 10 years old, super high levels of LDL. And we got to interview Dr. Bernstein, by the way, which was a huge get for us. All of this got packed into this movie, which includes what happened when we finally got the results that were featuring in this paper and how exciting that was at the time

it was occurring. it's actually a really good film. I mean, obviously I'm biased being the protagonist in the film, but it's really Jen and her team that made this thing so amazing. I'm really excited for it to finally get released. We think it'll be sometime in the fall. And when it comes out in the fall, it'll be like streaming online. People can, you know, go pay to watch it or that sort of thing.

It'll be on a major streamer. We don't know which yet because it's being negotiated right now. Okay. Amazing. And what about the research and the charity work? where do people go to support that? They can go, thank you for the plug. They can go to citizen science foundation.org.

That's quite literally the website for our charity. It is a bona fide 501c3 public charity, so your donation is tax deductible. And again, not only is this how we make it happen, but as I mentioned to you offline, we have effectively a 0% admin overhead. The only money that's going from somebody's donation is just for credit card processing fees or donor box,

which is the major platform we work through. Last I checked, I believe we have that accounted for something a little bit above 4%. So something in the neighborhood of around 95% of every dollar we're getting is going right back out towards the research with us not taking a single penny of it. It's amazing because that's how we were able to get the first study done. This one's going to take a bit more money. The triad study is going to be 100 people again if I get my way. for the main group,

but we're also going to have a control group of another 100 people. It's going to cost quite a bit, but we're actually really close. I want to say we're about three-fourths of the way there last I checked. Oh, incredible. And we'll put the link in the show notes below for that.

And also exciting on that same note is that you are launching your own podcast, right? That's right. And it'll be out maybe sometime in the summer? My hope is by the time this airs, it'll actually be out. I was originally aiming for June, but because of the paper dropping,

I have a reason to try to launch it a little bit sooner. I've been... What should people be searching? It's going to be called the Feldman Protocol. Okay. It's, uh, there's a little, there's a little bit of an inside joke for people who followed me all along. That's what it used to be called when I was showcasing how I could drop my LDL cholesterol by just actually over consuming a huge amount of fat, including saturated fat, because it was like

almost a trick. But that was the initial inversion pattern that I was discussing more in 2016, 2017. So while the name, while that term had kind of disappeared, because I did. want people to keep associating it with me and using it for like getting better life insurance and things like that because that sounded prescriptive. I thought, oh, you know what? I'll see if I can bring it back for the podcast name. And I tried that along with other names and everybody seemed to universally like that the most. So hopefully, knock on wood, hopefully by the time this gets launched, we'll have that up and going in. I'm going to try to twist your arm to show up.

You come to Vegas now and then, right? Yeah, yeah. I need to come on the show. We'd have a great discussion. Well, I'm excited for all of those things and so much more of what you're up to. And I think in this new wave that we're in, we have so many individuals who are taking health into their own hand and asking these big questions and saying, how can I move this along further? And how can I contribute somebody of work that can at least push us towards a direction of looking into things that we've assumed to be true for so long? But there might be more to the story. And I definitely see you as being one of the people that's doing that in the best and most integrity-filled way. So thank you, Dave, for coming back on the podcast and talking about this paper,

the implications of it, and all the questions that need to continue to be answered as part of that process. So super appreciate you, brother. Thank you for having me.