Why Isn’t Lower LDL Ending Heart Disease? – TFP #025 | Philip Ovadia

So, I from a very young age knew I wanted to be a surgeon. Wow, this is very interesting.

Yeah, my parents swear that as early as 5 or 6 years old, people would ask me what I wanted to do and I didn't say I wanted to be a doctor, I wanted to be a surgeon.

The belief that if you're eating real food and you're only eating plants, that's better than eating real food with meat. Is I think at this point demonstrably false. And I do think that meat is essential to our optimal health. I think that even though it's the tide is shifting somewhat. Today's population does not want to think the food environment is as bad as it is. For their health.

Yeah, I mean we're definitely I think maybe coming to a little bit of a reckoning. And what's really, you know, I think kind of got to me more and more over the years, right? As I was doing heart surgery and especially became magnified when I went on a low-carb diet because I was overweight, I was pre-diabetic and >> [music] >> I was headed for my own operating table, so to speak.

Tell me who you are and what you do. Thank you, Dave. Great to be here with you. I am Philip Ovadia. I am a heart surgeon who now is on a mission to keep as many people as possible off the operating table.

Yes, you aren't a lot of times people think, "Oh, heart doctor, probably like a cardiologist." But specifically you're a cardiothoracic surgeon. Correct. So, you you get in there. I get in there. I hold the heart in my hands. I do the most common operation I do is what's called a coronary artery bypass. So, this is when heart disease has reached its very advanced stages and we don't really have options anymore for things that are a little bit less invasive like stents. We're in there literally redoing the plumbing essentially to deal with blockages that have accumulated, also deal with problems with the valves that can occur in the heart. But we what I do is is a end stage of this disease process. And what I really came to recognize, you know, throughout my 20, 25-year career now is this disease really shouldn't get to that point. It shouldn't need something like that. And the reason that it does so much is because I think we're focused on the wrong things as the cause of the disease and therefore we're doing a lousy job at preventing it. And we instead need to rely on treating it with these maximally invasive things like heart surgery.

Yeah, this is something I definitely have been looking forward to unpacking with you because as you know, it's it's a big focus of my research, but I'm coming a bit more on the lipid side. I go on a low-carb diet. And right up until the point that I'm going on a low-carb diet. I'm like gaining a little extra weight, but I'm looking around at my, you know, same class. And seemingly we're all gaining weight and I seem to be doing better than they are. So, my BMI gets up to like maybe 26, which for, you know, 10 years ago seemed pretty decent cuz I had a lot of other friends that, you know, were doing a lot worse than I was. And therefore I like to compare this to smoking a lot. It's like, "Oh, you know, 60 years ago I would be the lower smoker." >> [laughter] >> Yeah, so I'm not as bad in relative terms to everybody else I know. But definitely more and more I see is what's happening to us with our metabolic health on the outside often reflects what's going on on the inside. Would you say that's been your experience?

Yeah, definitely so. And, you know, exactly what you said about heart disease being normal, right? It is the number one killer. It has been now for over 100 years and it's almost of something that's kind of inevitable and maybe we can do a little bit to slow it down and, you know, you might die of something else first, but you know, 25% of people that die die of heart disease in this country still. And what's really, you know, I think kind of got to me more and more over the years, right? As I was doing heart surgery and especially became magnified when I went on a low-carb diet because I was overweight, I was pre-diabetic and I was headed for my own operating table, so to speak. It just sort of occurred to me, you know, why do we accept that this is still the number one killer? And, you know, maybe kind of how our paths ultimately crossed was I said, "Well, if cholesterol is the cause and we know this and we have treatments for it, then why are we still here with it being the number one killer? Like why haven't we had a significant impact?" And that is really I think the key question that doctors in this field don't ask enough. Like if we know what causes heart disease, why haven't we fixed it?

Yeah, I there was gosh, I was forgetting who it was I was talking to. But they were explaining how in the '70s it was almost a kind of euphoric revelation that Brown and Goldstein so effectively proved that it was LDL cholesterol. Such that this doctor I was talking to who was considering, you know, becoming cardiologist, his friend his advanced doctor friend was saying, "Oh, I don't know that there's much reason for you to go into that. Like that field's probably going to start going away because we're going to, you know, with these powerful new drugs, we're going to get LDL low enough that it's going to be an orphan disease and heart disease just isn't going to be a disease of the future." That proved to be wrong. >> [laughter] >> That we're we're getting quite sophisticated in medicating down LDL levels. So, in your opinion, why isn't that working to take away heart disease?

Yeah, that's really the question we need to answer. And you know, I had the similar experience, right? I was going through the early part of my surgical training and deciding what subspecialty to go into and I decided I wanted to go into heart surgery. And my mentor was told me, "Absolutely do not do that. You will not have a job. There is going to be nothing for you to do." You got the same advice. >> And I got the same exact advice. This was, you know, 1998, 2000 and here we are and not only is there not a job for me, there was actually a shortage of heart surgeons in this country now. There are not enough heart surgeons to do all the heart surgery that needs to be done. So, it tells you, you know, what has happened during that time and the question why, right? We should be answering that. You know, we should be asking that first of all. You know, cholesterol is the cause is what I was told my entire medical education, my, you know, entire career as a heart surgeon, cholesterol is the cause. We have gotten better and better, like you said, at treating cholesterol. We can bring those numbers down to extraordinarily low levels and yet heart disease isn't going away. And you know, again what was so interesting when we first met, right? Which is now 6, 7 years ago. Yeah. And doctors and the medical system look at that question and say, "Well, it's because we don't lower it enough. We don't lower it early enough, right? We need more, more, more." And you as an engineer, right? Stepped back and said, "That can't be true, right? [laughter] Just this system, right? We haven't fully explained the system, right? At a minimum what you could say is, "Okay, maybe cholesterol is part of the story, but obviously there must be more cuz lowering cholesterol does not have the magnitude of impact that you would expect it to if it really was the majority of the story." And so, you know, you have to start asking, right? What else is going on in the system? What else are we missing? And I continue to be amazed today that my colleagues within the, you know, traditional medical space, they don't ask that question. The only thing when I ask them, right? I confront them. I say, "Why is this patient on my operating table when they've been taking medications to lower their cholesterol for 20 years? And they're within the guidelines." And all they say is, "Well, I guess we should have started it earlier or we need the more powerful medications to lower it even more." And they literally cannot fathom that there must be other stuff going on that we haven't accounted for.

Yeah, I there's this um I'm not sure if this is a real fallacy per se. I think it's an offshoot of the No True Scotsman fallacy, but it's I like to call it the Preacher's fallacy, which is when you see the you know, the um example of some fringe church where the preacher says, "Hey, I can heal anything so long as the whole room believes strongly enough, I can make, you know, this person walk or something. Okay, I'm going to try. Okay, is everyone in the room focused? Okay, cuz you you've got to believe strongly enough. Oh, it didn't work. You guys weren't believing strongly. I need the whole room to feel so it's it's a it's something that cannot be effectively quantified enough. But at the time I was getting into this space, there wasn't PCSK9 um inhibitors. Now you actually have a drug complement that can get like practically all the way down to zero. And so you would think that that would be easily the trials that would yield effectively cardiovascular disease risk-free populations in the intervention group. But we don't see it there either. We we see what they would consider to be a strong efficacy, but it doesn't actually just eliminate the heart disease or the progression of the heart disease. But getting back to what you're describing as the questions that I of course want to ask everybody, but particularly people are into heart surgery, is okay, why is it such a small effect size assuming that we're acknowledging together that it is a component of atherosclerosis? If it's the central driver, why aren't things like PCSK9 drugs at just doing what we thought Brown and Goldstein were taking us in the direction of practically taking it entirely out of the equation?

Yeah, it's a great Well, I mean, we know the answer, right? But getting that message out is so important. And you know, what's interesting is doctors, [snorts] right? When you go to the kind of the larger doctor community, there'll be this acknowledgement. They'll be like, "Well, yeah, of course cholesterol isn't everything, right? We know there are other things." But in practice, they don't they don't implement that. They don't pay attention to the other stuff, right? They'll be, "Okay, stop smoking, great, right?" But you know, you get to things like insulin resistance that we know are so important. And they ignore it. They don't measure it. They don't look at it. Maybe they, you know, they're starting to be a little acknowledgement in a roundabout way because we have these things called GLP-1 medications that sort of affect insulin resistance. And yeah, they also reduce heart disease. And oh, by the way, they don't actually reduce cholesterol. They might raise it, but somehow it's still helping heart disease. And somehow this all still makes sense, right? You get into this roundabout thing, but in the end they just it it comes back over and over again to the cholesterol question. And you're right, the PCSK9 inhibitors, right? These should be the proof, right? If it was all about cholesterol, we should see massive reductions. And you know, we see reduction, but I would say it's nowhere on the scale that it should be, right? If this was the story. Uh and we then start to see the tradeoffs for those reductions, right? Cuz I've seen the patients with their LDLs in the single digits. And there's some stuff going on that can be very concerning. Uh and overall in the trials, you're like, "Great, we reduced cardiovascular disease by 40%." But patients don't live any longer. And they might actually live a little shorter depending on which trials you're looking at. And then you're like, "Okay, well, what's going on there?" But again, this is part of um I think the problem with the medical system as a whole is it's not the cardiologist's concern whether you die of something else. It's only their concern whether you die of heart disease. So they're like, "Well, great, I reduced it 40%. My job is done." And you're like, "Well, but the patient feels miserable and isn't going to live any longer." And you kind of get stuck there, right? Cuz they're like, "Well, not my problem." Which is another interesting part of our medical system these days. It's it's it's a bit of an issue that I am obviously very passionate about. I mean, the the very first question I jumped to when my cholesterol skyrocketed 10 years ago was, "Okay, I do see data that shows there is this association between LDL levels and cardiovascular disease. Okay, but that's one way of dying. That's one way of affecting, you know, possibly health span, maybe, right? But what about all non-cardiovascular disease-related outcomes? Are they unaffected? Do they Are they affected? Well, associational data should at least give us a quick gut check. And if low LDL does not have any tradeoff, presumably the people who do have like, say, genetic abnormalities where they have lifelong low LDL, will just live longer. They'll live longer than all of us. And that's the one question that I've asked a lot of people who are in favor of lowering LDL. Why aren't you interested in this data as much as I am? Because 10 years ago, when I was trying to find anything on this, I could not find anything that suggested that no, those people with lifelong low LDL do in fact live longer than the rest of us. And again, we I would say we have pretty good data on that right now. You know, we have the PCSK9 loss of function. We can even look at the as much as I hate to say it, the Mendelian randomization studies, right? And they show exactly the opposite. They don't live longer, and they may actually live a little shorter, you know, depending on which study you're looking at. And you know, you're exactly right again, but that question doesn't get asked within the medical system. Um the just the way that the medical system has evolved is such that, you know, the people that are focused on heart disease are only focused on heart disease. And this is another question about cholesterol, right? That now goes through my mind. And admittedly, 10 years ago, 15 years ago, I wasn't thinking about this. I wasn't asking these questions, right? I was a heart surgeon. My job was to take care of heart disease. And you know, we did what we had to do for that. Um but you know, cholesterol um as a whole, right? What else is it there for? What else is it doing, right? Within our bodies. And if we're focused on lowering it, right? What are those other effects that we're going to have? And you know, even even going back right to the statin data, um you should be able, if heart disease is the number one killer, and statins are okay, we'll call it, you know, moderately effective at reducing heart disease, well, then we should be able to easily demonstrate that people taking these medications live longer. And again, you don't. You can't. Um it's uh so those are questions we definitely need to, you know, get more into the mainstream, right? And it's so interesting within this community, right? Within the low-carb metabolic health community, that people do talk about this. And people do think about it. And and we, you know, the challenge, right? Is now to get more and more of my colleagues thinking about that. You know, when I'm talking to my cardiology colleagues and my other heart surgeons, and you know, I don't tend to lead the conversation with, you know, "You're wrong about cholesterol, right?" >> [laughter] >> I just start to ask, you know, "Well, what else should we be thinking about, you know? Why aren't we seeing these reductions? Like, why do you have so many patients who you have on these medications for years and years and years, and they still end up with the problem, right? They still end up needing stents, bypass surgery." Um why is it that patients who have a stent or have bypass surgery, okay, who are now right right [snorts] in the crosshairs of hairs of the medical system, okay, we're doing what we call secondary prevention, right? So these patients get treated the most aggressively. Why do the majority of them still die of heart disease? That should be a central question that we should be asking. And in a lot of ways, I feel sad about the medical system in that we don't really think big enough, right? We don't think about curing heart disease. We think about managing it. We don't think about curing diabetes. We think about managing it. Um and it's really uh kind of unfortunate, I think, these days that we don't you know, there aren't more cardiologists and heart surgeons saying, "I should be out of a job." Right? They should have been right 20 years ago. Right? There shouldn't be this much work for us to do. And uh the reality is is that most cardiologists, most cardiac surgeons are too busy to even think about that cuz they're just overwhelmed with people that are sick with heart disease.

Uh I think that if if I'm to represent the, you know, the devil's advocate in the room with regard to the existing all-cause mortality benefit of cholesterol lowering, many would say, "Well, the trials are not powered to capture all-cause mortality benefit because they're only powered enough to capture a benefit in, say, cardiovascular disease mortality." Now, I have my own response to that, which is that well, first of all, we can't then say that we know there's a benefit in cardiovascular disease mortality without having the rest of the balance sheet. You Because dying less of one thing doesn't mean you're not dying more of something else. You need to be able to know that. The other the other I guess I can say gripe that I have is if you're wanting to make a mortality benefit period, I think you need to be able to state that with all cause mortality. Because again, if you don't have all of the data in hand, that's a problem. Moreover, I don't love it when there's an existing trial that does show or asserts that there's a cardiovascular disease mortality and yet the all cause mortality, even if not statistically significant yet, is showing the intervention group at higher levels as though it's trending in that direction. I give it to people to say, well, currently it's not statistically significant. But the skeptic in me is like, why not at least give it enough time to find out if that trend would continue. Why is Why are these trials set up in such a way that they can be ended early with the emphasis that wait, we hit this statistically significant threshold on particular endpoints that we were interested in and therefore now it's unethical to continue it any further. To me, I get worried that that's uh a bit too artificial that it in fact should be time based. And if anything, you can extend on the time, but making it event based, I'm worried is a bit too it's a bit too problematic for clouding the data.

Yeah, I know. I agree with that completely and I even zoom out more than that, right? Cuz I don't take care of trial participants. I take care of patients, right? And then I look at If you just look at the population data, right? Population level data, we should be seeing the impact, right? We've had, you know, statins, the first statin came in the market, right? 1983, 1984, right? They've been the most widely prescribed class of medications now for 30-plus years, right? Where's the impact? Um again, since I got told, right? Don't go into heart surgery, you know, in the year 2000 to today, heart disease has gotten worse by any metric you want to look at. Um we did have some improvements, right? Initially in the 1980s, 1990s, probably mostly attributable to the change in smoking rates. Um but, you know, where is the impact from this treatment of lowering cholesterol? That's where I look at at a high level. You're exactly right about the trials, right? The trials are stacked to show what the companies behind the trials and the investigators behind the trials want to show. Um I share the same concerns, right? When you look at the 4E trial for instance, right? The blockbuster trial that led to the approval of PCSK9 inhibitors and you see that the trial was stopped early after 3 and 1/2 years, supposed to be a 5-year trial, supposedly because of a benefit in cardiovascular deaths. Um and you see that the total mortality in the treatment group is numerically higher, not statistically significantly higher, but numerically higher than the placebo group, you should be scratching your head and saying, "Hmm, there might be something to this, right?" And you say, "Okay, well, this is, you know, this is how trials work." But why weren't those patients followed out to 5 years? Like that could have been done. It's been, I believe, 4 years since that data was released and we haven't had any follow-up. Some reason I don't think anyone's interested in knowing what the follow-up data shows, but yeah, I mean and even more so, right? When I ask my When I say that, you know, that directive statement to my cardiologist, okay, PCSK9 inhibitors were initially approved because of the 4E trial, do you know that there were more deaths in the treatment group than the placebo group? I don't think I've met a cardiologist outside of the low carb space that is aware of that data. And let's This is also why I have a tough time with just clinical trial data in the first place. I do appreciate that there's the the larger dream of randomized control, right? Where you actually can have Because randomi- The concept of randomized control trials are so powerful in that what you're trying to do is you're trying to make the confounders you are not aware of meaningless. So, once you can randomize, but as I've talked about many times in this podcast before, I don't love running periods. Running periods have a lot of problems, particularly in that they may diminish the perceived level of side effects that could be, but it also may just actually impact the trial itself. I don't love this event based cutting things off and I I don't love how all cause mortality is not a common place. Again, if you're not making the claim of a benefit in mortality, then But if you are going to make that claim, then I feel like you should have it powered for that as well. But there is this other factor, which is just that these are all based on business models. So, naturally, what comes to market, it's a survival of the fittest factor. And And here's Here's the challenge that I'm pretty sure you can relate to. I genuinely try to, quote unquote, stay in my lane. I don't want to make any statements that could be taken as advocating for or against any kind of treatment, right? And And on top of that, I'll qual- I'll further qualify that even beyond the things that I've just said now, I don't really do a lot of research into these drug trials because the data's just not as compelling to me, not just for those reasons, but also because drugs do a lot of different things. You You can say, "Hey, this drug lowers X." But really, it also affects Y and Z and A and B and C and all kinds of other things. If the drugs that lowered LDL cholesterol had a likewise effect across the board, I know it's presented to us that way a lot, but I have pushback on that. If they were very consistent across all the drug trials, across all of the data, distinctly, then I would feel differently about that. I would say, "Okay, then the other things that they do are less relevant." But a great example are statins. So, statins are considered quote unquote the gold standard and many would argue it's because of the degree with which they lower LDL as to what their efficacy is. But I've also met and have talked to many scientists, not just, you know, cardiologists, who will say, "Well, actually, we're wondering how much of it are things like the anti-inflammatory components." And in a person for which there is a very high degree of systemic inflammation, it may be that it has unique efficacy and that's very common for secondary prevention. Again, the engineer in me thinks, "Fortunately, you're setting up a scenario of need of a possibly a manufactured deficiency and then meeting that deficiency for this very distinct subset of the population and then assuming it applies to the rest of the population. That's That's my concern. And that's why we needed to study people who are metabolically healthy with high LDL to find out if there is this association between the LDL and the development of plaque.

Yeah, I mean, again, that's really the big challenge here, right? cholesterol lowering for what it is supposed to be, right? Within the cardiovascular space, um that is another big open question. Does this apply to everyone equally? Uh and the obvious answer is no, of course it doesn't, right? Even when you look within the data of any one trial, right? There's variance. There's, you know, the bell curves, the responses, right? That vary so much. And yet we just want to say this applies to everyone, you know, uh universally. And you know, cholesterol lowering I really do struggle to think of another example within medicine where we have, you know, universalized, right? A uh recommendation so broadly. Um it it really is one of the few areas where we say, "Yeah, everyone needs this." Um And it's just not The data Yeah, the data just isn't there, you know? Again, zooming out and looking at the big picture, right? It obviously does not, you know, on the one hand, right? You have to say, "Well, it must not work as well for everyone as it does for certain people." But cuz we see failure after failure after failure, right? I have, you know, at this point, it is probably more unusual for a patient that ends up on my operating table not to have been on a statin for a long period of time. Um so, obviously, all those patients failed treatment, right? We can argue why, but they have failed treatment. Uh and then you have the other side, right? The question, obviously, that you're focused on in that, you know, we have this growing group of people who the marker that we're concerned about is um outside of the desired range, we'll say. And yet they don't seem to be getting the disease in droves like we would expect. And, you know, now we want to get some more data on that and, you know, maybe under the hood the disease is worsening and they will down the line, but maybe not. And if they're not, maybe that's pretty interesting, right? Even if it's a subset of them, right? That aren't getting the disease as we expect. Okay, well, why? Right.

>> Let's let's dig into this and um you know, there are so many you're right, there are so many problems with the trials, right? Whether we're talking about the surrogate endpoints and we're talking about the, you know, you know, the confounders, right? And the adjustments. And, you know, again, I always say, listen, I'm just a simple heart surgeon, right? Uh I'm really not a statistical expert, but I can look at a paper and the longer like the section is about, you know, how they needed to adjust and what kind of, you know, manipulation they need to do with the data, like that's an automatic red flag. Um when I was in medical school, uh I worked in one of the surgical labs, right? And we were doing basic science research. Uh and I had this English post-doc who had the best saying that stays with me to these days, you know, to this day. Uh and he said, "Statistics should be used like the drunk man uses a light post for support, not enlightenment." [laughter] That's great. >> And, you know, that's been a big influence, right? Cuz I read these papers and I'm like, well, if you need to do all of this manipulation, right? If the raw data doesn't really show you what you're looking for, you're probably not looking at a significant effect.

Yeah, I don't I and I'm I'm going to bring it back to smoking. Do we need a lot of calculations, modeling, etc. for there to be those associations that seemed so compelling to so many people for smoking being likely causal? And this is this is with that full acknowledgement that we haven't done a a big RCT with smoking versus non-smoking. It'd be considered unethical right now. And so, a number of people are comfortable enough going by Bradford Hill criteria. He's he's, you know, one of the ways by which you can do further evaluation outside of an RCT to say, "Hey, I can't say with complete certainty that smoking causes, say, you know, lung cancer." But, wow, the Bradford Hill criteria, strength, consistency, temporality, all of that, oof. The threshold is extremely high, right? And with the threshold being that high, I can feel comfortable enough making that claim of causality. If you look at these drug trials that provide that observational data, how much are the people putting this together assembling a methodology section that's like 18 paragraphs on they had to adjust for this confounder and adjust for that confounder and so here's their, you know, fifth level of model. And only after that point could they feel confident that they could show those numbers assuming all of the other adjustments are appropriate. Well, I this is why like I keep pointing this out to my friends who love observational data. Listen, every single time you run something like a sensitivity analysis where you're saying, "Hey, I know how much this thing and that thing and this other thing are confounders against the one thing I'm the most interested in." You're actually making a causal claim for each of those. You are saying, "I know how much there's a cause by thing A. I know how much there's a cause by thing B in order for me to know what's left over, the remainder for thing C, right?" Again, you don't need to be advanced in stat- statistics to recognize that all adjustments are based on assumptions. They have to be. Better, in my opinion, when possible, to stratify over modify. Go get the group of interest and study them in particular. Why would we say, "Hey, I think high LDL cholesterol is bad for those people who seem to have some adaptive state such as being on a low-carb diet where cholesterol might be higher for a physiological reason?" Now, I'll fully concede that that's a hypothesis on my part, that's what I've published on and so forth. But, there already should be a bunch of people in the field, your colleagues, who should be saying, "Hey, this is this is actually pretty great. We have a population that has high LDL absent those other confounders that are normally needing to get adjusted for, right?"

>> Yep. This is a huge scientific opportunity. Let's study those people who have the high LDL absent that. And lo and behold, no, not not as of yet. I've yet to know of any It may be happening and I'm just not aware of it yet, but as far as I know, we're the only team that has been prospectively studying people with low ASCVD risks, but otherwise extremely high levels of LDL cholesterol.

Yeah, and you know, we have other data that should lead lead us there, right? So, I'm aware of both statin trials and PCSK9 trials, right? That have you know, looked at the cohorts based on insulin resistance, right? Their metabolic health. And again, pretty consistent, right? The patients that are in good metabolic health have low insulin resistance. They don't benefit from taking these medications. And, you know, that should be another sort of thing that gets us to a similar question, right? Cuz I would broaden it out. I would say, "Okay, we don't even have to focus on the low-carb people. Let's just look at the people that are insulin sensitive." Right. And what do we see in those patients? And again, those studies don't get done. Um And of course we understand why, right? Again, going back to the business model, right? You don't want to demonstrate who doesn't benefit from taking your medication. >> Right. Right. >> You know, so I understand it, you know, from I guess the, you know, pharma standpoint. But as a practitioner, right? That is exactly my job, you know? This patient that's in front of me, what is the best management for them, you know? What should I be worried about and maybe what doesn't apply to them? And of course, you know, now as a practitioner kind of focused in with this space, right? The low-carb metabolic health space, this is sort of the central question that I have to ask for the majority of patients that now show up to me. Um and not having Well, I mean, I'll step back and say, and I know you won't say this, right? But I'll say it. I think I have enough data, right? To be pretty confident in telling that patient today that no, you're not going to benefit from cholesterol lowering. And yes, we do need to monitor your disease. And if we see that your disease is worsening, we need to figure out why, but again, I'm fairly confident at this point saying it's not because of your cholesterol level. May have to do with your cholesterol quality, may have to do with other things going on, inflammation, insulin resistance, you know, other things that are going on, but the data in my mind as a practitioner is actually good enough for me to say it is valid for you as a patient if you choose not to go down the cholesterol lowering route, I don't think you're putting your life at risk. Um I think we need to watch it carefully. I think we need to be looking at a lot of other things, but cholesterol is not the answer to this problem in and of itself. And we'll work, you know, we'll work on all the other stuff. We'll look at all the other stuff.

So, have our have our one paying the bills moment. We're this this podcast is sponsored by us by by Own Your Lab. So, continue getting your private blood testing through us and then we can keep this, you know, very commercial free. But, this is from our desk. We have our team and they occasionally feed me some questions for whoever the known guest is that's coming up. So, this one's for you. Um The name of your book is Stay Off My Operating Table. We haven't gotten into your book yet, too. Which isn't something you usually hear from a cardiac surgeon. What led you to becoming an author?

Well, um what led me to becoming an author was uh the desire to be able to scale this, right? To get this message out to more people. Uh and I realized that a book is one of the ways that could happen. Uh it wasn't really something I was thinking about, to be honest. Uh I guess the real answer as to what led me to being an author is I became connected with a uh ghostwriter and he said, "Did you ever think about writing a book?" And I said, "No, I really haven't." And he said, you know, I said, "Well, what are what would I write a book about?" And he said, "Well, everything you do, you know, what you tell patients, you know, how you think about this." And I said, "Well, this isn't going to be a very long book. It's going to be like three words, eat real food." Like that's [laughter] the book. He said, "No, no, no, we we got something here." So, uh we started working together and uh we wrote the first first book, Stay Off My Operating Table. Uh currently working on a second book, Stay Off My Kitchen Table. And um it turns out that, you know, books are good ways to get this message out at scale. And um the book is really Stay Off My Operating Table is really the guide, you know, what I do with patients, what the program looks like. Stay Off My Kitchen Table, the new book is going to go a little bit more into why we do that, why we think that's the right approach. Um and uh it's just, you know, I realized, right, that as a practitioner it's limited how many people I can work with ultimately. And a book is a powerful way that more people can get this information. And uh you know, the book's been out 4-plus years now, and it continues to be unbelievably rewarding each time I get an email that says, "I read the book. I made the changes. You know, all this great stuff has happened, right? And I didn't need to talk to that people that person, I didn't need to see him for an appointment. They can do it on their own. And that's another kind of focus of my messaging, right? The the health care system as it is is very disempowering to patients. You need a medication, you need a surgery, you know, you need us to do it for you. And one of the other things that I think is so amazing about the low-carb community, the, you know, metabolic health community, whatever you want to call it, is it's giving the power back to the patient. You don't actually need the doctor to do this for you. You can do it. You can change your health, you can be, you know, in charge of your health, and you can get the outcomes that you're looking for. And in the end, you might need less input from doctors, right? You might need not to be on my operating table, you don't need me to fix it for you. And of course, I guess again from a health care business standpoint, that's not a great message, but for really helping people change their lives, that's the message that we need to be getting out there.

I think it's a great title. I think that the to your point, I think it's a very serious problem with the medical community in general. So, and a lot of what I hear in a response, which you with even opening the topic of lifestyle, diet change, etc., is it's just not what patients want. Almost as if And I I'm trying to find a kinder word to use, but it's almost as if there's a prejudicial impression of what they anticipate patients are going to be like. And make no mistake, there are absolutely people in my life, in my orbit, who that is how they function. They only go to the doctor to find out what the doctor can give, and ideally whatever the doctor gives, it's uh going to allow them to continue the lifestyle that they consider to be the one that they can't change. And part of what I wish for those very same people is that they had doctors, you know, like David Unwin and others who I think have a a little bit more of a considered discussion with them. That, no, actually with some degree of, you know, putting forth new habits, being aware of what foods you're eating that may not be as good for you. You know, it's it's not as you don't have to be in a kind of defeatist state. And that the only place, a lot of the folks I'm thinking of food is their one quality of life from their perspective. The one thing that is their one and only big joy is that food, which if it sounds a lot like a drug addiction, frankly, I feel like it's very comparable, right? But I have seen in my own family people who did break out of that. Who did recognize that, no, just, you know, it doesn't radically change every single thing about their life, they can make some choices that are better. And as they regain more of their health, they actually have more choices available to them for things they can do in life that turn out to really be worth it. And that they can be around for their family and so forth. But it is true, it takes a little more time. Takes a little more concerted effort. >> [laughter] >> It takes more It takes more support. I had uh Chris Cornell on uh a few days ago, I recorded with him, and he's into health coaching. I think there needs to be a lot more health coaches, there just needs to be a lot more of an apparatus that supports these lifestyle decisions, these changes. But it is true, I do get worried about how much the training for a doctor like yourself kind of sets the stage for this kind of a relationship with your patients. Hey, they just want in They just want whatever you can provide uniquely. And that really a lot of their health is not in their hands, it's not under their control.

Yeah, it's a big problem um and you're right, it starts with the whole sort of education, right? And the the, you know, I would call it the paternalistic approach, right, of medicine. Uh that the patients are dependent on us, right? That we need to do this. Um and you know, but on the other hand, right, that could be turned exactly to the things that you're talking about, right? Okay, you need the doctor to help you make the diet and lifestyle changes. So, how do we do that? And you're right, let's get the health coaches in there, you know. Uh let's get the right information. One of the sort of um I don't I don't know the right term for it, right? You know, a little bit underhanded, I would say, right, thing that happened is um we started saying, right, "Okay, diet and lifestyle matters, right?" But then we give patients diet advice that is so lousy, right, that A, it doesn't work, and B, they can't follow it, right? We've demonstrated this over and over and over again, right? Eat less, move more. It doesn't work, and patients can't follow it. Uh because starving is miserable ultimately, and if that's basically your only approach, it's not going to work, right? So, then we then use that in medicine to say, "See, diet and lifestyle doesn't work, right?" And it's like, no, that diet and lifestyle doesn't work. Um when you give people better advice, and you can explain to them, right, that eating, you know, metabolically healthy it actually isn't miserable, right? I I enjoy everything I eat, right? I probably I enjoy what I eat today more than what, you know, the enjoyment of my food that I got back when I was eating, you know, kind of a standard diet, right? When I was eating back then it was, like you said, maybe there's a little bit addictive, but it was just eating to like eat, and, you know, I can't really say, "Oh, I really enjoyed this." Um now, like when I'm more selective about what I eat, right? I'm choosing everything that I eat, and I choose it because A, I love eating it, and B, it does get me feeling better, right? So, I can have all those other side benefits. And I really, you know, and granted, I admit, right, I have a biased population that comes to me because the way my practice is set up, and because of, you know, who I am, and the audience that I have in all of this. But I don't really get patients you know, going saying that they were miserable, right, when they're eating low-carb, carnivore, whatever flavor it might be of it, right? They Yes, some of them fall off the wagon for other reasons, uh but no one really says to me, "You know what? I don't enjoy eating this, uh and therefore I'm not going to continue doing it." Uh which is very interesting, right? Cuz when you when I was giving the traditional medical advice and telling them to eat a low-fat diet, right, or telling them to, you know, just restrict calories, you know, you would, you know, they'd come back to you, and you're you're like, "Why aren't you doing it?" And they're like, "Cuz I was miserable. Like I didn't have anything I enjoyed eating, you know, and I didn't, you know, and I was hungry all the time." And, you know, again, my personal experience in this, and my experience now with, you know, the hundreds or thousands of patients, right, that we've been doing it with. Um they actually enjoy what they eat. Uh yes, you have to get them over sometimes that addictive stuff to start with, right, with the sugar and with the processed food. Uh but once you get them through that, and again, this is all about the empowerment. It's all about you can do this. Right. You know, you can, you know, you really don't need me, right? Sometimes I feel a little bad, like, you know, you're paying me this money, and I'm not actually doing anything for you. You're doing it, right? You know, and we get to a point where well, you know, you don't really need to keep seeing me. And they're like, well, but I want to. I'm like, okay, well, you know, then keep seeing me, but again, even in my current, you know, telemedicine practice where I'm trying to keep people off the operating table, my goal is to be able to say to them like, you've graduated. You don't need me anymore. Just keep doing what you're doing. And and it's such a different model for health care. And you

Know, that's really a broader discussion about how I think the health care system has completely failed and how we can change it, right? It doesn't need to be about low carb. It's just a better way of taking care of people, empowering them to take care of their health.

Yeah, I I think you really hit the nail on the head. I I'm wishing that there just was overall more of an awareness for people who are stumbling initially to recognize this difference between, you know, this might be a bit of a pejorative, but I had an engineering friend who put it this way, propping up medicine. Which is kind of like you you're doing enough to get them back out on the street to then go about their life, but with the understanding that they're circling back not long after that they were put back out again because of the fact that they're not given even the skills to consider what it is that they could do next.

I want to tell you a little bit of an anecdote. I want to be mindful of the personal information involved, so I can't give the full story, but I can say that there was somebody I know who went to get bypass. And they were diabetic and they were being very good about their low carb diet. And they had an easier time ordering low carb before the surgery than after the surgery. After the surgery, they were put on "a heart healthy diet." That was actually a standing order. They were they were there was some labeling in the system and the EMRs or whatever for which when they were trying to order from the kitchen, quite literally, the response was, "That doesn't have enough carbs. There needs to be enough carbs for this heart healthy diet." And I am floored that that's a real thing in 2024, 2025, whenever. But I guess there actually isn't for a diabetic, for somebody who's actually like diagnosed diabetic who has had huge strides being low carb, that there actually was an awareness of the carbohydrate content of what they were being served. The foods that they were being served. I see it every day.

I So, tell me, how are we with Okay, with diabetes in particular, Philip, how are we here in 2026? How is this really, really a thing? I but it it Yeah, it continues to floor me and the simple reality is is that the system is so far behind, right? The stuff that we talk about, right? The stuff that's out there about, and you know, again, this isn't like niche any longer, right? Virta Health has, you know, published this at scale that we can reverse type 2 diabetes. And yet, if you took 100 random doctors out of the hospital today and you asked them, "Can you reverse type 2 diabetes?" I would be shocked if 10 of them said yes.

Really? They really have zero awareness. The situation after heart surgery is even worse than you realize based on that anecdote. Because we demonstrated, this is actually one of the So, heart surgery is probably the leading area of medicine that focused on outcomes, right? And has We have a national database that essentially every patient that has heart surgery gets entered into the database, right? And that over the years, this has been around now about 15 years or so, you know, the database continually gets formed for, you know, how do we make the outcomes of surgery better, right? How do we make surgery safer, less people die. And there has been a demonstrable reduction in the mortality rate from heart surgery over the past 20 years because of this. So, it's it's at the forefront of what we, you know, like to call quality based medicine, right? And one of the earliest things that was demonstrated out of that database was the better that you control a patient's blood sugar in 48 to 72 hours after surgery, the better the outcomes are. So, we put we are very aggressive about managing patients' blood sugar around the time of surgery. And this means that a lot of patients after heart surgery, they are getting continuous infusions of insulin to keep their blood sugar under control. Okay? And this is standard of care now in the hospital when you get heart surgery done. And I will routinely walk in the morning after surgery and the patient literally has insulin going through their IV to control their blood sugar. And there is a glass of orange juice and a plate of pancakes in front of them that are low fat, heart healthy, carb controlled, right? Cuz the concept is, well, if we're giving them insulin, we don't want their blood sugar getting too low, so we have to give them a certain amount of carbohydrate to balance that insulin. And you know, again, like when I, you know, walk into a room and it's a new nurse, right? Who hasn't worked with me before or it's a new hospital cuz I do like travel work, right? And I say, "Well, how about we take away the pancakes and lower the insulin?" They'll be like, literally [clears throat] it never occurs to that, right? It doesn't occur to the dieticians or, you know, the nurses, right? Whoever's managing all of this that, well, if we put less carbohydrates in, we would need less insulin to keep their blood sugar under control. This is still a foreign concept within the medical system despite all of the evidence, right? That we see. We have to acknowledge that low carb, right? Is still a very micro niche, you know, within the health care system.

This is so disappointing to hear. [laughter] I'm sorry. This is because we we do have data, decades old data, going to type 1 diabetics. We find industrial strength levels of exogenous insulin. No problem giving it to them in massive doses. And sure enough, what happens? We have this high association with the exogenous use of high levels of insulin and cardiovascular disease, right? Exogenous insulin, cardiovascular disease. Yep. Now, we're talking, I mean, we're talking decades and decades ago. I for the documentary, I got to interview Dr. Bernstein. The OG, the GOAT, right? Engineer becomes a doctor. And he did, unfortunately, he did die last year, but he died at age 90. For for not just a type 1 diabetic, but he was patient zero for continuous glucose monitor because he actually adapted the device so that he could monitor it himself. And he's the one who, the original who is saying, "Let's go by the law of small numbers. Since I'm type 1 diabetic, why not just go ahead and have less glucose coming in, then I need less insulin?" I can definitely see with my fellow type 1 diabetics that they're dying at very high rates for high levels of insulin that are coming in. So, yeah, I can completely understand why this per what you just said, I can completely understand why it is that there is this impression that controlling glucose "controlling glucose" with keeping it high enough that then the insulin can counterbalance it would probably have greater efficacy for those people, or I should say, would have a better association for those people for which you're successful in bringing the glucose levels down, relatively speaking. Emphasis, relatively. Man, I would love to I just love to be a multi-billionaire and I would absolutely want to prop up an RCT on low carbers. Just like get people on a low carb diet against those people who are on this train, this high glucose um from the food infused with with insulin levels to control it. I I really want that, like I want that right now.

Yeah, [laughter] no, when you find the funding, honestly, like, you know, heart surgery, right? Again, would be the like gold, you know, you could, you know, cuz we have again all the data, right? About controlling the glucose, right? So, if we took this to the next level and said, "If we can control the blood glucose levels with less insulin, right? Do we see those same benefits like you said that we know in the type 1 diabetics, right? The less insulin they use over their lifetime, all of these complications are lessened, right? The heart disease, the blindness, the, you know, vascular disease that leads to amputation." Um, this again is a very personal thing for me, right? My older brother is a type 1 diabetic. Uh, and, you know, for 40-plus years of his life, right, it was all about balancing his carbohydrate intake with his insulin, right? I remember early on, you know, when he was diagnosed, right, and I was probably 8, 9 years old and he was like 12, and, you know, the calculations, right, of how much insulin to give based on how much glucose he just had or, you know, how much carbohydrate he just had. And then, you know, things evolved, right, and he got his insulin pump and now he could do this a little better, right? And all this time, right, the goal was, well, you know, balance your carbohydrates with your insulin. We're trying to keep your A1C under seven. Um, and um, then of course I stumble into low carb, right? I hear about Dr. Bernstein, who I had never heard about, right? Again, being in the medical system, I think if you took 100 endocrinologists and asked them have they ever heard of Dr. Bernstein, you'd probably get 95 nos. You know, this is another problem. Um, and um, you know, so he led that life. Thankfully now he is, you know, learned from me and now much better controls his glucose with a lot less insulin and is on a much better path. Uh, and why this isn't the standard of care for type 1 diabetics, no idea. [laughter] And like I said, it again it's not I don't know of a doctor who is aware of Dr. Bernstein and wouldn't implement that with his patients. Um, but the sad reality is is that the vast majority of endocrinologists managing diabetes have probably never heard of Dr. Bernstein. They probably haven't seen the Verda data, uh, you know, showing you can do this at scale with type 2 diabetes. And uh, again, it's the challenge that we're all working on, right? Getting more and more people to hear about this and then it becomes, you know, do you want to do this top down and try and get this word to all the doctors, or do you want to do it bottom up and try and get the word to as many patients as possible who can then go to their doctors and say, "Well, why didn't you tell me this? Why don't you know this?" Um, you know, and I think ultimately you need some of both. Uh, but it is a challenge.

I I don't know why I don't I don't know why I don't just get used to this. It's uh. I don't I mean, it's I think I think part of it is that I'm a technologist and we're in the information age. It's it's available. You can you can go to my computer, you can go on your phone. You can look this up. You can look this up right now. And but I'm also I'm also acutely aware that cholesterol has become a I lament this. Cholesterol has become such a powerful red herring, I think. Because it ends up becoming this rather simple answer to this broader question of relevance. It's like, okay, well, if we know that cholesterol is the central driver, that's the CliffsNotes over here for cardiovascular disease. These other things like I went to an NLA conference and um, what they like to do at these conferences, and I'm sure you're already familiar with this, they like to like break out case studies. And with a bunch of doctors in the room, they can do Q&A and ask, "Okay, so what did you do, you know, that here's here's the case, here's the blood work that was run, and it's like a puzzle. And how can we solve this puzzle?" And without exception, every single time, wide spectrum blood testing, everything, they never test fasting insulin. You never know if there's hyperinsulinemia. Now, you can get a sense when you look at the lipid panel because often they have the low HDL, high triglycerides, which would be a poor man's version of metabolic health. But insulin levels alongside glucose can tell you enormous amounts of information. And we have Joseph Kraft to thank for that.

Yep. Both both Bernstein and Kraft, by the way, should have Nobel Prizes. I don't care if they're awarded posthumously. It's just they they should have it. In both these cases, they helped to further illuminate just how much diabetes and heart disease come back to this dysregulation within the body related to these conditions and how much insulin exposure is relevant towards these cardiovascular disease outcomes. We have enough to not necessarily draw a straight line, but we have enough to compare it to LDL cholesterol. And that's why I say over and over again, you don't you can absolutely believe in the lipid hypothesis, full stop. Just please do me a favor and make a comparison in those hazard ratios against what we already see with things like hyperinsulinemia, with things like metabolic syndrome and so forth. Don't let this topic suck up all the oxygen in the room to the extent to where you can't, uh, you know, have any additional thought paid to these other specters that are so much larger.

I I'll just I'll just wrap it up with this one point. It's fascinating when we look back in time to things like Eisenhower's heart attack. And it's a huge mystery. What, you know, what could it be? And that started the whole saturated fat debate. But of course, looking back, well, duh, the three packs a day might be kind of relevant. You know, it's possible. It's possible the food he was eating could be pretty relevant. But the three packs a day, I think a lot of us would believe played a huge part, but there was such an impressive blind spot to that because of how much of a desire there was by the general populace to feel that smoking wasn't that bad for them. I think that even though the tide is shifting somewhat, today's population does not want to think the food environment is as bad as it is for their health.

Yeah, I mean, we're definitely I think maybe coming to a little bit of a reckoning, but, you know, the other choice that was made back then, right, was, okay, you know, we're going to not talk about the smoking part. We're going to talk about the food, right? But you had two prominent camps that were looking at the food back then, right? You had Ancel Keys, right, in the cholesterol focus, saturated fat focus. And you had Dr. Yudkin, right, who was talking about sugar, right? And there was a very intentional choice made back then that we're going to go down this cholesterol route. Um, and, you know, what? Okay, we had two competing hypotheses. We have to choose one. Okay, so we're going to go down this route. Uh, but, you know, now here we are, right, all these years later. And I would say that the cholesterol hypothesis around heart disease, right, is incomplete at best, right, being generous. And no one even remembers that Dr. Yudkin did all this work, right? And then Dr. Kraft came behind him and did all his work with insulin resistance. Cuz you're right, the magnitude is like overwhelming. Um, the most ardent cholesterol, you know, believers, right, in medicine, you ask them, right, so how many patients that, you know, end up on my operating table or, you know, have a stent placed, right? How many of them have whatever we're defining as high cholesterol these days, right? And usually the numbers are somewhere 50, 60%. Dr. Kraft showed that 90-plus percent of patients that showed up with a heart attack had insulin resistance if you test for it properly. I think he even made a famous statement like, um, the He said he, yeah, he basically said the patient with heart disease without um, insulin resistance, you just haven't looked for it hard enough.

Right, it's. Undiagnosed. Yeah. Uh, hyperinsulinemia or something like that. Which, to be fair, it it it was kind of a categorical statement which we would probably disagree with, but the 90% that might actually hold up. Yeah, yeah. I mean, cuz, you know, he did an all-comers study into his hospital system, you know, everyone that rolled in the door with insulin with a heart attack, right? He tested them by his method for insulin resistance and 90-plus percent, right? Um, so again, magnitude of effects, right? You know, this is a a thought experiment, right? I'd love to go, you know, whatever, the American Heart Association meeting, or, you know, you get a large group of cardiologists, you know, together, and you said, "Would you rather have a patient, right, with an LDL of 40 and an A1C of 7, okay, versus a patient with an A1C of 5.4, and we won't even really go super high, right? Let's say an LDL of 130." Yeah. Okay? I can almost guarantee you that probably 95-plus percent, right, are going to take the low LDL with the obvious diabetes versus, you know, a well-controlled A1C with a little bit high LDL. I think you're exactly right.

Yeah. And, you know, again, we we have forgotten that the other hypothesis even existed. And I think part of why I feel so confident that you're right is because I I have family members and friends who have been given comfort by their doctors for when they've gotten their LDL low. There's There's two friends in particular that I think of who, I mean, effectively have the impression they're heart attack proof. But, one of them has several markers for metabolic syndrome, and one of them has all five. Yeah. But, they have their LDL levels down in the bottom level, you know, I want to say under, I don't know, under 60 or under 50, something like that. And so, from their perspective, they're like, "Oh, well, it won't be heart disease. You know, I do have to worry about other diabetic complications." Newsflash, if you're worried about any diabetic complications, let's fix the diabetes. You're Yeah, you're at a heart attack risk, unquestionably, given the present data. I don't know how you can come to any other conclusion.

Yeah, no, exactly right. And and, you know, and again, I see it all the time, right? Cuz, you know, sort of the reverse, right? Cuz we have the patients who fixed their diabetes, they go on a low-carb diet, and forget about the lean mass hyper responders, right? Cuz we know that the average data shows us that cholesterol doesn't change, right? Population-wide, you know, Dr. Unwin's data basically showed that the LDL didn't change in his low-carb population, and yet those patients will still, and again, I see this all the time, right? They go to their doctor, and, you know, they've dropped their A1C from 7 and a half to 5.5, uh and, you know, they their LDL, right, ends up in the 120, 130 range, and they get told, you know, uh first of all, it gets blamed on the diet, even though the cholesterol may have been the same before they started the diet, but most doctors don't even look at that, but they still get told, you know, that this diet is killing you because your LDL is too high. Um, and it just It It's actually, and we're published on this, for what it's worth. We have um a meta-analysis of 41 randomized controlled trials that had at least one arm that was low-carb, and low-carb enough to where it might have affected LDL levels. Go to cholesterolcode.com/papers if you want to find the one I'm talking about. To your point, yes, David Unwin's population is going to be typically higher BMI. If you are higher BMI, this is a per our own study, if you are a BMI of, let's say, 25 to 35, and you go on a low-carb diet, it is unlikely your LDL will change too much. Yeah. Uh to your point, it wouldn't be surprising at all to have an LDL go from, say, 120 to 130. That's a negligible change, right? This, by the way, happened with my dad and my sister. Their LDL levels went up just like a tiny bit, whereas mine doubled. Um that's what happens for people like myself who tend to be BMI of, like, say, 25 or lower, and our meta-analysis supports this. In fact, the lower the BMI, the higher the change of increase in LDL levels. Now, interestingly, though, if you have a BMI of 35 or higher, so very definitely well into the, you know, the side of obesity, and you're moving down into more overweight, but not quite lean, um typically LDL levels go down, if anything. But, to your point, what is very common is when somebody is making a lifestyle change, and what they're telling their doctor is, "Yeah, you know, actually it turned out I just need to cut out the carbs. Now I just have, instead of, you know, a cheeseburger, I have three patties with bacon and cheese on, and just I skip the bun, and it worked. I've like lost all this weight, you know, it's my blood pressure's down, and my um now I'm able to do like some running, where before I couldn't run anymore." And I think it's a bit of motivated reasoning. I think that the a doctor is going, "Oh, okay, but that does sound a little concerning. It's a lot of red meat, it's a lot of saturated fat. Let me look at your Your LDL levels are above 100, right? I'm worried that this diet is contributing to LDL cholesterol, and it's going to give you a heart attack sooner." I have never in my life had so many people express opinions of concern for the diet that I'm on, not just my doctor, but but hanging out with friends, when I'm doing something like having, say, three burger patties with cheese and bacon, or something like that, who did not bat an eye when I would have loaded fries or hot fudge sundaes, or we would have a giant pizza, right? Or or just pie or something, you know, things. [laughter] things that I think are more objectively concerning. Although, I don't know. I guess there are many people who might be watching this now who go, "No, no, no, no, the three patties are much more concerning than the hot fudge sundae." I never know anymore. It's just funny to me how much you get the side eye. [laughter] on low-carb choices. Yeah.

It It is amazing. Um, you know, I'm optimistic this is starting to change a little bit. Uh, again, I don't think it's really the majority, but, you know, I think there is more awareness of this now. Uh, you know, the recent changes, the new food pyramid, it's going to help. Um, although, in a weird way, because of the politics affiliated with it, it's sometime you know, you almost have people now arguing for processed food, which is just simply amazing to me. It's like, you know, I I guess we. Your three words. Yeah. We can argue about how much impact, you know, uh. [clears throat] uh, you know, more processed food might have on our health, but I can't imagine anyone arguing, but it does happen, right, that these things are beneficial to us in some way. Uh, and that's kind of the weird place we find ourselves in that like people will now defend, right? No, you got to have the processed food, right? It's essential um in some way, but uh, you know, again, I am optimistic that I think the environment is starting to change. I think people are recognizing this. Um How do you feel about the new dietary guidelines? Do you feel like that's been a big. Yeah, I think they're a great start, you know? They're not the whole solution, right? There maybe are some minutia in there that we can start to argue about, but just the fact that we have, you know, a flipped upside down food pyramid. [laughter] We had a Super Bowl commercial talking about "eat real food," right? You know, we we have a government website that is realfood.gov, right? These are all things that are at least starting to change the, you know, the zeitgeist around our food, and I think more and more people are paying attention to it. And ultimately, that is the first step, right? Getting back to kind of what we talked about earlier, right? Getting back to that basic acknowledgement of what you eat is the major determinant of your health.

Yes. Um, and, you know, again, I used to think. Most doctors wouldn't don't acknowledge that, you know? They're like, "Nah, what you eat doesn't really matter. It's your genetics, and it's your, you know, lack of medication basically that's causing you health problems." I used to think that myself. I used to think that health was, you know, in a pie chart that a third of it was exercise, a third of it was diet, a third of it was random chance, genetics, environment, fill in the blank. The me of today, I want to say it's maybe 85% minimum is what I am consuming. It's what you're consuming. And this is not to diminish the importance of exercise, you know, regular exercise to some degree. But, how much diet in particular is so impactful to health, I think it's just so unquestionable now.

So, bringing it back to the the food pyramid again, or the upside down food pyramid, I'm fascinated by how much there's a division within the low-carb community, and that number of people like, "Oh, thank goodness, this is such a massive step forward." And then I have some friends who are like, "This is closer. There is at least more of an acknowledgement of real food, but for example, the saturated fat limit didn't change. How can there be more of an interest in things like low carb even if the the pyramid seems to reflect a little bit better if you're not changing something like saturated fat, then what do you do?"

Yeah, no, I I mean, I acknowledge that point, but I think we have to kind of take the victories, right? As [laughter] they come, right? You know, and uh we have to acknowledge, right, that undoing 40 years of, you know, beliefs isn't going to happen overnight. It is the biggest, I think everybody can agree with this. It's the biggest single change Oh, yeah. that I things happened in my lifetime. Yeah. With the dietary guidelines. And and, you know, the the saturated fat part of it, um, you know, it's in the footnotes, right? It's in the document that most people don't read, right? And, you know, yes, you and I have a lot of the same friends and I can imagine who some of those people are that are, you know, hyper focused on that aspect of it, but the reality is is that, you know, the old food guidelines, no one read the 150-page report that came with it. The new food guidelines, I think very few people are reading the nine-page report that came with it. Um, and the saturated fat is a footnote, you know? They're going to look at that pyramid, they're going to say, "Okay, I should be eating the stuff that's at the top." And the reality is is, you know, the average person doesn't think about saturated fat. Right.

Right? You know, they don't read the food labels. Well, and right there in that upside down pyramid, there's a number of meat products, for example. Like just the concept of the dietary guidelines moving towards more of a plant-predominant diet is you know, fairly much it's fairly a given. And there was, you know, you got Eat Lancet that also tries to press that it's also for the benefit of the planet. It's not even just for individual health. And this to me, it felt like there was a shift. It's a bit challenging because as you kind of alluded to, there's a political component to this. But do I feel like by and large the average person that I know in my life seems to be a little bit more aware of metabolic health and the value of eating real food. I feel like I've seen this more in, like say, the last year. I never know though, cuz I also have a lot of friends that are low carb, so that might be a factor.

No, I I do think in the general population, there's an awareness, right? I was uh, you know, one of the things that I think was great about the food pyramid is it did put meat at the top, right? And it started to again counteract that push towards plant-based diets. Um, and uh, you know, this is something that we talk a lot about in my upcoming book. Um, you know, eat real food is the base, right? But I do think there is enough evidence uh that I'm comfortable as a physician saying meat is essential to health. And plant-based diets are an improvement over junk food, right? Over a standard Western diet, we'll call it, the old food pyramid even. Um, you can demonstrate that. I acknowledge it. But uh the belief that if you're eating real food and you're only eating plants, that's better than eating real food with meat, uh is I think at this point demonstrably false. Mhm. And I do think that meat is essential to our optimal health. You can be healthy if you're only eating plants and if you supplement properly, uh, but I don't think you we can say that you can be optimal anymore without eating meat. Uh, so, I was very uh enthusiastic to see that they put meat pretty prominently up in the upper corner of that thing. They put whole dairy, you know, whole fat dairy, uh real dairy, I would call it, up there. And yeah, there are some veggies. And, you know, the way the way that I explain it to people now, you know, my advice as their physician is um you can eat the veggies if you want. For a lot of people, they're not harmful, uh, but they're not essential. And there are some people that do have demonstrable harms from eating, you know, plants. Uh, so, carnivore is an option. It's not the only option, uh, but it is a valid option, and of course, you know, we know plenty of people that have thrived on this. Um I really don't know people who thrive on a vegan diet. Uh and it the ones that are doing better than they were doing on a standard Western diet, you know, on a junk food diet, they can do that for a while, and the more um, you know, the better planning they do, right? And and getting the right supplements and balancing their protein sources within the plant kingdom, uh, you know, it's very hard, and you can do it for a while, uh, but I have now seen over and over again that that breaks down over the long term, and uh that's part of the uh discussion we have in the new book about uh what the role of meat as an essential part of the human diet is.

I have a complex opinion on this. I'll I'll play a kind of devil's advocate in that there is there is a handful of people I know who are on a plant-only diet. Or I guess some of them would even say they'd prefer I just say animal-free diet. It is true that the two the two people that I have in mind who I've known for a long time, who I know are truly just plant-predominant, are both very aware of the supplementation. This is this is a big deal, I think, that can never be understated. Even for those people that I know that are doing fairly well, they're mindful of things like B12 and vitamin D. You want you just you want to be mindful make sure that you get that. It's things like B12 deficiency, you may not realize for a while.

Mhm. And then it can rear its ugly head, and it's it's a really big deal. So, I I think I've seen enough at least anecdotal data that there are some people who seem to do well on a plant-based diet. That said, vegans themselves will acknowledge there's a high recidivism rate. And one of the more fascinating things that I watched happen in real time, but I I remember having tabs on her in my mind after I saw it, was um uh Super Size Me. Mhm. Morgan Spurlock, I want to say. His wife was a very famous vegan chef. And I hope I'm reciting this story properly, but she had um she had ultimately determined that she had to leave veganism. And what had happened to her was even in spite of being like very successful in the movie, you know, brought up her profile a lot, she was eating with a friend, and she just was watching the friend eat a steak, and it just became like overwhelming to her that she really wanted to eat that steak. And I I kept thinking, wow, that's like that's a big deal. If you if you ever would have somebody in a position where their profile's built from it, they've got a long span of time of being not just um a strong adherent to veganism, but in addition to that, being excellent at, you know, good vegan dishes and so forth, to have this unique desire to consume meat. It does to me suggest that even for as good as she was in putting things together, that there might actually be some deficiency that was getting met with the steak. I'm always fascinated by the concept of um desire towards the complement of amino acids that would be typical in animal food. Yeah. But yeah, there are a number of people who've been long-time vegans that ultimately fall off. But to be fair, are there, for example, some carnivores who've reintroduced plant-based foods? As of the time of this recording, of course, the more famous case is Paul Saladino. Uh, but I'll also point out that Michaela Peterson, I believe, has also started reintroducing some things because she feels like she can tolerate it now.

Yeah. Yeah, no, I mean, there are certainly examples of that, and that's why I say, you know, no, I don't I'm not convinced that carnivore is the answer, right, for everyone. But I think it's a very valid option, and I think there are a lot of people who need it at least for a time period, right? And Michaela is a great example, you know, and I think people with these autoimmune conditions um are a great example. And I think it's great, right, that they have gotten to a point, right, her in particular, you know, her story, that she has healed to the point that she can reintroduce these things. Um Now again, at least from what I've heard from her, right, she didn't do it because she felt there was some deficiency in her carnivore diet, right? She did it because she had to be so restrictive and she doesn't want to be so restrictive anymore. And great, you know? And I think Paul, you know, um and Paul and I have had this discussion, right? It's great that Paul thrives now on the diet that he thrives on. Um But I also don't think that that's the right answer for everyone, right? For I think the people who try and say, "Oh, look at, you know, what happened with Paul and carnivore doesn't work." Right? I don't think that's a, you know, great argument. I think uh Paul is a very unique situation. And I see others like that, you know, that are in his situation, right? They're very young, they're very active, they're very lean, and they just can't get enough. Now, I and and again, I've had this discussion with him, you know, I said to Paul, "I think you could have made other modifications, right? Maybe you needed to be more high fat within your carnivore framework." Uh, you know, maybe you had other things, right? That you could have modified that could have had similar good results that you got from adding back carbs. Um and again, that's why I right? I I'm not here saying carnivore is the only option. Uh I think carnivore is a good option. I think we need to get that message out there more, right? And especially, you know, coming from the heart disease space, uh this again circles back, right? Cuz here I am in the heart disease space saying, "Not only is red meat um not harmful, but I actually believe it is beneficial and essential. And if you have heart disease, um which again, going back to our earlier point of Dr. Kraft's work, that means you have insulin resistance. You probably should be looking at a low-carb diet that is very uh uh heavy in animal products."

Yeah, I I so a few different things to unpack there. Yes, it it really can't be understated that we're right now in this moment in time, you're one of many who've sat down, who work with human hearts, who is of the position that no, not only am I not saying don't limit your say red meat intake, but actually you can see people benefiting in their cardiovascular disease health by being on a diet that may be entirely red meat, right? To be fair and to expand on your point, um this is a very I know the the word restrictive might be considered pejorative, but it's a restrictive diet. It's saying, "Hey, we're we're limiting things intentionally." And why is that being done? Well, like in the case of Mikhaila Peterson, that was the one way in which she could feel normal. It's the one way in which she could like live life. There are a number of people who I remember when in like forums would almost call it a trap, like the carnivore diet trap, because some of them, once they went on a carnivore diet, they felt so good and recognized that now they um because it's a it's a good multiple removal diet is a is a term that's used for like a diet where it's very narrow. But you've removed so many different types of foods that if there was something you had an allergy to, a sensitivity to, an intolerance to, then you'd know you've categorically dropped all of these things off so that you could then find out that oh, I do. I have some kind of allergy or intolerance. That's the value of a multiple removal diet. What what normally is the protocol of a multiple a multiple removal diet is to introduce things one at a time. And usually intentionally by a lot. Mhm. To see if it perturbs, if it activates that intolerance, right? Carnivore is really, really, really good for this because I I don't know that I know anybody who has an intolerance to red meat. Like an actual, like they have a unique allergy, something like that. So, in being on that, they can then find out if there's an effect. And on top of that, you will be low carb, you'll be ketogenic because you have no choice. You're going to become fat adapted.

Yeah. Well, okay. Now comes around this other factor, which is that okay, I may or may not have found out that I have some kind of intolerance, but I really do want to have other kinds of food. You know, I miss salad. I want to have salad. Can I have salad? Probably. Probably most diabetics can have salad, right? It's a low starchy, you know, it's but something different like potatoes, it's different. Some some of my family members are diabetic to the point that a potato is going to be a problem for them, even though it's pretty fibrous, right? Yeah. I have a family member who's very diabetic, really loves strawberries. And we at least try to work out the timing of when they consume it, which can be helpful. But there's just no getting around it. They are just that insulin resistant. If I could, I'd have that person just on a carnivore diet because of how insulin resistant they are. And so getting back to this is the major thing I wanted to come back around to is Paul Saladino is very physically fit. The carbohydrates he's reintroduced, I'm confident he's burning off like crazy. Mhm. He's surfing all the time. Yep. He does a whole lot of outdoor activity. And this is where I turn to a lot of my sedentary family and friends and I'm going, "Recognize the context. When you look to a fit influencer, as they're as they're commonly referred to, and they were low carb at first and you found when you went low carb, it was helping you out a lot and then they said, 'Oh, you know what? I've changed my mind. Now I'm I I find I do well, you know, having fruits and a whole bunch of other things.' Just be sure that if you're still following along with them, if you're not if you're not the activity level that they're at, that's another version of lowering carbs."

Yeah, [laughter] exactly. Glucose by burning it straight up. And if you don't have a body that's great at handling glucose because of this diabetic dysregulation internally, uh it's going to be relevant as to whether you can do what they're doing.

Yeah, very true. And again, you know, this is where, you know, I'll bring in with my patients, right? We have a great tool that you can use to demonstrate this, right? Put on a CGM. And, you know, all those questions you're asking me about, "Can I eat this, you know, how much of it can I eat?" Put on the CGM and let's see what the data looks like.

Beat it. No, you can't beat it and it's an amazing tool. And again, this is another area that I'm optimistic, right? Because now they're over the counter. Um I hear less of the objections from other doctors about, you know, for some reason a CGM shouldn't be put on, you know, this population or that population, right? I get so frustrated about that. I I feel like uh Philip, I feel like there's just sort of a number of people that if the low-carb community is interested in something, it's like they've got to take the other side of it. And a CGM, I I believe that pretty soon we will have non-invasive CGMs such as an Apple Watch, a Samsung Watch. Oh my gosh, I wish it was here tomorrow because I do have people I care about who I want them to wear a CGM and they're going, "I'm not going to. That's not going to happen." Okay, fine. Um Would you wear a watch? Yes. Come on, technology, bring it to us. I'm confident and I'm sure you are, too, that a sizable number of the population is going to find out that they are diabetic, didn't know that before. Once it's just a feature on the watch, Mhm. That's what they need. Yeah. I'm quite positive that that will actually be a a kind of mini revolution of sorts. And that now people will start really caring about what their individual level reaction is to various foods because you basically have an oral glucose tolerance test that's always on. So, you'll you'll become more aware of the foods you're eating and particularly if you're overstuffing yourself, which I just wish more people were aware of in general.

Yeah, I think, you know, again, going back to the discussion around the food pyramid, right? If if we were able to get rid of all of that and just say, "Eat in a way that your blood sugar doesn't go up." That revolutionizes health, right? And going back to the work of Dr. Kraft when it comes to heart disease, right? If we did that, I am quite confident that the impact on heart disease would be just massive, right? Would put all of this cholesterol stuff to shame. Um if we just told people, you know, "Eat so that your blood sugar doesn't go up." And again, it's a very simple entry point within my practice these days of, you know, people come to us and they have all their, you know, beliefs about what they can and can't eat or what they should and shouldn't eat. And um these days it's just "Put this on for 2 weeks, watch the curve, and note when it goes up and when it doesn't go up. And the stuff that you eat that it doesn't go up, just start eating more of that, right? And that is a very simple way to get people headed in the right direction. And it doesn't need to be, you know, it it doesn't need to be a diet that you're starting, right? A camp that you're in, you know, low-carb, carnivore, vegan, whatever it is, right? It just eat so that your blood sugar doesn't go up. We know that blood sugar, you know, is the predominant thing that is damaging the blood vessels that then allows the cholesterol to become problematic, right? When it comes to heart disease. And we know that, you know, the effects that blood sugar is having in the brain now that leads to um neurocognitive problems and psychiatric problems. And we know the, you know, how glucose fuels cancer. And we know all of these diseases that we're worried about, right? They all tie back to the same thing. Um if your blood sugar isn't going up, you're going to be at a lot lower risk for all of these things, most of these things, you know. There are a few exceptions, but uh if we could just reframe our whole health care system, I would say, around controlling people's glucose levels, uh the the impact would be massive. So, I share your dream that we're going to have, you know, soon enough the uh glucose monitors that are non-invasive. Um and they won't be perfect, but they'll be good enough that people will be able to see the impact of what they're eating and everything else that they're doing in their daily lives on their.

blood sugar levels. And you know, that's going to get us uh. It's, it's going to be the biggest game-changing device in a while. I uh, I'll, I'll expand on what you were saying just now. It's not so much whether the glucose levels go up, it's whether they're controlled.

So, the, yeah. >> So, it's true. If you're on a in range. Yeah, if you're, if you're, I would, I would say this to a family member right now. If you're wearing a CGM, whatever you're eating, if your glucose levels after the meal, two to three hours later, are back below 100, you're probably fine. Right? Like if it started below 100, it ends up being persistently below 100 as opposed to a a hypoglycemic effect where you like dip way down and then you're in the roller coaster. Um, you're, you're likely metabolically healthy.

Because in the case of someone like Paul Saladino, I'll bet that that's what's happening. He eats, you know, bananas along with other things that are in his meal. And because of his metabolic health, his level of activity, etc., his liver glycogen stores are like, "Give me, give me." And he gets a whole bunch of those and he's repleting more glycogen stores in his muscles and so on and so forth. Again, it's fine. That's the metabolic state you're in.

But if you're wearing one of these CGM or someday wearables, and your glucose levels remain persistently high, they go way up and they're staying up there. Okay, well, that's the whole reason we did an OGTT back in the day was to see, "Oh, no, after so many uh, so many hours, no, you're actually not seeing a return to normal because you have an inability internally to control your glucose levels given all else being equal, given the state of things."

So, let me jump. What I'm normally doing with guests is I'm usually doing a bit more of their biography on the front end. Um, we're, we're switching it up. And I'm, I'm going back in time now, a little bit deeper into the podcast. But this was fun, kind of jumping in from this direction. Let's go back to when you determined you wanted to be a heart surgeon. When did that happen?

Um, so, I uh, from a very young age knew I wanted to be a surgeon. Wow. >> This is very interesting, yeah. My parents swear that uh, as early as five or six years old, people would ask me what I wanted to do. And I didn't say I wanted to be a doctor, I wanted to be a surgeon. And um, I have no idea how that would have happened, right? I have no doctors in my family. I have no surgeons certainly in my family. I didn't have surgery as a kid, something like that, right? Um, but somehow that was my path. That was my destiny. Um.

Not astronaut. >> No. Not fireman. Yeah. >> Those usuals. Yeah, exactly. >> Have. You're like, "I want to put my hands into people." It was something was driving me to that. Uh, so, you know, uh, throughout high school, I did things to kind of fuel my interest in medicine, you know, volunteered at hospitals, you know, those types of things. Knew I was going to go to medical school. Uh, so, I actually went to uh, what's called an accelerated uh, undergrad med school combination pre-med med program, it's called. And uh, then I, you know, got through medical school. And again, knew I was going into surgery. Uh, so, uh, I started a surgical residency. And uh, back when I did it, it's a little different now, but you know, uh, pretty much almost all of the areas of of surgery, you would do what's called a general surgery residency. It's about, it's five years usually. And then about year three, you would start picking what area of surgery you wanted to specialize in.

And so, you know, that brings me to the story I told earlier. Heart surgery just fascinated me from both the technical aspects of actually doing the surgery and the physiology of the heart. Um, you know, putting people on the heart-lung bypass machine, you know, we actually stop their heart, do the surgery, start it back up again, hopefully. Most of the time, yes, successfully. Um, but it's just, it, it's kind of just an amazing, you know, technical feat and it has all this great physiology. And so, it really grabbed my attention from, you know, early on. And uh, despite my mentors trying to dissuade me from it, I decided, you know, I wanted to go into heart surgery. And so, after completing my five years of general surgery training, went on to do a fellowship, two years in specific in cardiac surgery. And uh, haven't looked back. Never regretted that decision. It, I still love doing it to this day.

Let's unpack that a little bit because I think that a lot of people hear about this from outside. They're not actually realizing exactly what you just said, that there's a real technical component that for as much as it has advanced, for as seemingly routine as it might seem for how many of these operations take place on a daily basis, it's actually um, quite a big deal. The heart is not meant to stop. Nope. It is meant to just keep rolling all the way to the the very last day. And it actually is not Hollywood, you know, they're pulling out the defibrillator and they're like, "Ah, shock him." And it's, and it sounds like it's just like jump-starting a car. >> [laughter] >> Right? Like it just try it again. Shh. Ah, we got it. We got it going. But in reality, it's, it's very electrical. And in fact, the defibrillator part of what it's trying to do is get this this perfect cascade going. It does. It's not a muscle in that it doesn't just like squeeze in one direction. It's actually kind of like a series of straps. Would that be a good way of putting it? >> Yep. That has to conform in a very distinct fashion. And it really, even this is a little bit of an oversimplification, but it could be argued it's kind of doing a uh, a two-way process. One direct. It's almost like a figure eight. One is heading its way into the body, the other is heading its way up to the lungs for this exchange back and forth between oxygen-rich blood and carbo hi uh, CO2 rich blood that's meant to go back out for the exhaust. And the issue is that what you're trying to do is hit pause. And this is where the bypass part comes in. You're trying to say, "We need to simulate what the heart is doing for the patient." And that was a gigantic feat in medicine for the longest time. >> Yep.

Do you, I actually don't know this, but I'd be curious. Do you know how old bypass actually is? Like? Yeah. So, yeah, and you as an engineer would find this fascinating. So, John Gibbon was the first surgeon that successfully did bypass in a human. Uh, John Gibbon um, and this maybe was part of the destiny of my story, right? Cuz he worked at the medical school where I went to medical school, Jefferson Medical School in Philadelphia. Um, so, John Gibbon uh, when he was a trainee doctor, you know, uh, young doctor in the 1930s, had a patient that died of what we call pulmonary embolus, right? So, they have a big blood clot, goes to their lungs. Uh, and when these get big enough, it basically the heart can't pump effectively and the patient dies. And he said, "If we had a way that could have supported this patient's heart during this, you know, we could get them through it." Uh, it was 30 years of work essentially for him to develop the heart-lung bypass machine. He worked um, he actually had to reach out to engineers at IBM uh to help him with the design of this system, right? Cuz um, you need to pump the blood around. You need to put oxygen in, take carbon dioxide out. Because remember, we're not only taking over the function of the heart, we're also taking over the function of the lungs. Right. Um, because of the anatomy, you basically can't bypass one without the other essentially. Uh, so bring the blood out, pull the CO2 out of it, put oxygen into it, pump it back in, do this without having the blood clot, do this without damaging the red blood cells, you know, and the platelets and everything else, you know, all the cells that are in the blood, right? It was a massive uh, technological engineering feat. Uh, so 1954 was the first time this was used in a patient. >> Wow. So we've only been doing this for 70 years. Um, prior to that, uh, the, the, the whole history of heart surgery is fascinating. There were some unbelievable things that went on uh that, you know, just today, like, you know, IRBs and stuff like that, right? Trying to get some of this stuff like no way that any of this would have happened today if we were trying to start heart surgery today. But prior to his work, essentially, it was believed that, you know, uh, you, if, if you tried to operate on the heart, you know, patient would die. Right? There were some things you could do before that, but, you know, basically, uh, 1954 is the first time he did it.

Another fascinating historical thing. So, um, uh, most of the problems back then were uh, what we call congenital defects, right? People were born with holes in their heart or, you know, things that weren't flowing in the right directions. There are all sorts of things that can happen as the heart is forming that will cause trouble. Uh, and so the original cohort of patients were all patients with holes in their heart essentially. Um, but remember, we didn't have a way of actually looking at the heart from the outside. Uh, so the only way they could kind of guess where the hole was was listening to the heart and what we call murmurs, which are sort of the abnormal sounds that occur when the blood isn't flowing exactly as it should. Uh, they would diagnose based on that and some rudimentary uh, EKG, looking at the electrical patterns, what was wrong with the heart. So, uh, the first case they did, um, successful, young lady had a hole in the upper chamber of the heart, what we call the atria. Uh, and technically that's easy to fix surgically, we'll say. I mean, back then it wasn't, right? But today, pretty easy to fix. Um, so they do the first case, it works great. They do the second case, and what they thought was a hole in the upper part of the heart was actually a hole in the bottom part of the heart, what we call a ventricular septal defect, which is much more complicated to deal with even today. And back then they really couldn't deal with it. Patient dies. Third patient, same thing happens, patient dies. So three cases, one survives, two dies. John Gibbons says, "This is never going to work. We're not doing it anymore." And stops doing it. Really? >> Other doctors, you know, elsewhere in the country had kind of been aware of what he was doing, and they picked up the work, and uh, you know, it then became, you know, what it is today. Uh, but yeah, people don't realize like we've only been doing heart surgery for 70 years. Uh, this, I think is another aspect of it that was so sort of fascinating to me. And um, you know, it really, I guarantee though, there's going to be a ton of people who are going to say, "70 years, that's like a huge long time. That's a lot." But to your point, uh, the, in medicine, things go slow. Yeah. I know. And I've been in the sausage making. I've got a lot of complaints to make as an engineer. >> [laughter] >> About how slow things go. Uh, but to be fair, it really was a huge feat. You know, I want to, I want to draw attention to two more things in what you just now described. A lot of people probably don't realize that the, the blood, the blood is quite literally is made to be very clottable. Like that's actually by design. Right. Half of the cells in the blood are immune cells. And it's for good reason, because when we have an an opening, when we have something that's hemorrhaging, the body on its own, without us actually being, we may be unconscious at the point that we're, you know, dealing with some injury or something, it needs to be able to attend to it on its own. So when you're handling this, this, this freeway of blood that needs to be on demand at all times to all cells everywhere throughout the body, you have to solve for that, and then you have to solve for the blood pressure. Just not like blood pressure, probably people are just thinking about it in terms of, "Well, you just like, you know, you're hitting a little throttle or something like that." It's like, "No." These, what's normally going is, you know, the term stroke is this specific um, hemodynamic, you know, pressurized push that just goes and goes in a particular, you know, way. Actually, that's a good question for you that I don't know myself. Are you simulating the strokes of blood moving through circulation? Or is this a different style of throughput?

Yeah, so you can do it both ways. The, with the way that the heart-lung bypass uh pump works, um, you can actually do it both ways, but the vast majority of the time, uh, we do it uh, with a continuous pump that actually doesn't cause a systolic diastolic. Got you. >> It's a flat blood pressure. Mhm. You're maintaining the blood pressure at, you know, a certain level, but it's flat. It's non-pulsatile, what we call it. Um, the studies between those two methods, cuz you can do it, you know, you can have a pump that basically causes a pulsatile output, uh, but it really, it's more complex and it has never been shown to be better than doing the non-pulsatile method. So the vast majority of bypass is non-pulsatile. Interesting. >> So we're maintaining a constant blood pressure, uh, but it doesn't have systole diastole. And the body tolerates that for shorter periods of time, right? Um, if you start getting into longer uh, this is one of the problems that comes up. The longer you're on bypass, you might start to see some issues related to that. So we're well into the weeds here, but I can't help but >> Yeah. Uh, bring this up. I'm very, you're probably familiar with VCAM with regard to atherosclerosis. >> Mhm. So where this gets really interesting is the nature of how everyone's always thinking in terms of, you know, blood's just flowing. It's like this river that's coming through. But no, this pulsatile effect that you're talking about, like you're just thinking about it in terms of it's coming through, it's slowing, and then bringing up. That's the diastolic to systolic thresholds. Well, at the sites, at the sites of endothelial cells themselves, there is some relevance to that slowing down and then speeding up and then slowing down. And this brings it back to the immune cells. Things like receptor binding potentially that becomes very relevant for the slow-down period before the speed-up period. Yeah. And VCAM is um, the process by which it's almost kind of like speed bumps to slow down to then capture Yeah. Immune cells that can then be differentiated into, you know, the most prominent example being monocytes into macrophages. But there are other things, neutrophils and so forth, for which the these things become relevant. But I can't help but wonder in what you just now described if there's a continuous flow, even if you're hitting a nice happy medium between, if that might have net detrimental effects. Yeah. >> Like that for the immune response. The catch is, it's such a short span of time, relatively speaking, that it may be not really that relevant. Yeah, um, you know, yes, during the short period of time, you know, in a typical operation, you know, we're going to have a patient on the bypass machine, you know, with this continuous flow for a couple hours at the most, you know, the more complex operations that we do, maybe we extend that out to six or eight hours, but we really rarely get beyond that. Um, now, what's interesting is we do actually have a uh, modern example of this, right? So we now have people uh, with what are called uh, LVADs, left ventricular assist devices, right? So these are patients whose hearts have failed. And uh, generally, they're awaiting a heart transplant. And we're basically using essentially, it's just heart bypass, right? So their lungs are still working, uh, but this pump, this device has now taken over the function of their heart in terms of getting the blood to circulate around. Uh, and those can be used for longer periods of time. Uh, Dick Cheney was a famous example of this. He had a LVAD in for I think almost a decade before he died because he wasn't a heart transplant candidate. So, he had what was called destination LVAD, meaning that you're going to live on this machine for the rest of your life. But, you know, so that's an example of where it's still that, you know, non-pulsatile that gets done long periods of time. But, you're right, there are consequences of that. They start to develop kidney failure. They're at higher risks of stroke happening. Um, you know, and there probably are other things, right? But, that's the trade-off because without it, their heart has failed and they're going to die. Uh, so, um, it's a very interesting uh, problem. But, yeah, from a uh, from your engineering brain standpoint, the cardiovascular system is, you know, uh, there are endless numbers of rabbit holes you can go down thinking [laughter] about how that whole thing works.

Well, I mean, there's just no getting around it. It's such a, again, going to the Hollywoodized version of things, it's oh, so-and-so needs an operation. The operation was a success. You very rarely see there were post-op complications. What are the nature of those post-op complications? What happens in this case and that case? One thing that I'm impressed by with cardio um, uh, with thoracic um, surgeons in particular is seemingly all of them, all of the ones that I've met have almost like an eidetic memory for the various statistics of different outcomes for what they're deciding to do. So, it's not, it's not like, "Hey, here's this new tool. And here's the study applied to the tool all by itself." They actually tend to be more skeptical within their field. And seem to be much more um, um, problem-solvers. There's, there is almost a little engineering, you know, style to you guys that I like where you're being very discerning and very skeptical on the approach of new techniques. And because I think a lot of it's just that there's more of a visceral connection. You probably have when there's bad outcomes, it's like right there in front of you. Much more so than a lot of other doctors who are like, "Well, take this drug for a while or here's a procedure we could do and, you know, maybe it'll be relevant or maybe it won't." It really is in your hands a lot more compared to other professions.

Yeah, I think that's part of, you know, what has kind of led me here from the sort of, you know, [laughter] standpoint, right? Is, yeah, you're, you're, I guess you could call it the right, the BS meter is a lot, that's more attuned because the outcomes of what we do as a heart surgeon uh, become very obvious very quickly, right? Versus, okay, you put a patient on a medication, you know, that's supposed to prevent them from having heart disease and 10 or 15 years later, they have heart disease, right? You know, and that's a failure, right? But, it's not as, I guess, the direct connection versus, you know, I'm in the operating room and if something I do goes amiss or maybe it's something with the patient goes amiss, right? The outcome becomes very apparent very quickly. Yeah, and and per the other example, you don't know as a doctor how much things outside the cholesterol-lowering medication were relevant towards the, you know, the outcome. Whereas what you're doing, you again, so much can happen literally right inside the operating room. And that feedback loop is very present in your mind, I'm sure. But then, the recovery period just post-op, there already is quite a lot. I think a lot, again, people need to not watch Hollywoodized versions of ER and see it up close and personal to get the sense of just how much is involved in recovery from like cabbage. It's, it's a lot, right? And there's still frankly, there's just a lot of things that can go wrong that's not anyone's direct fault necessarily. But, there's a reason why there's lots of constant, you know, monitoring, things like chest tubes, um, there's a lot. There's a lot of big, big stuff there.

>> And again, I think understanding the magnitude of that is part of why I'm here. Right? Because I really understand what happens when we fail to prevent heart disease. Right? Not blaming anyone or anything in particular for that, but I know the very real consequences when heart disease doesn't get prevented. And I think that's part of what makes it uh, you know, a greater magnitude thing to me to we need to prevent heart disease. We need to do a better job at preventing heart disease or arresting it at its early stages so it doesn't get to this very uh, you know, massive thing that I then need to do to go in and try and rescue this person. Right? You know, one of the things I've said many times before is no matter how good I might be as a heart surgeon, the patient is never going to be as good after I do the surgery as they would have been if they didn't need the surgery in the first place. >> Right. Right. >> And um, you know, again, I think that's part of why I'm so passionate about this, part of why I'm here is because I understand the true consequences of failing to do this.

That's very well said. I, for me, and I was actually talking to uh, to Mattis about this before the um, before we were recording. For me, the misdirect is part of the, the engineer in me is, it's not even just trying to get a sense of what all's going on and understanding it. I feel like so much of it, as we were talking about earlier, is already there. It's already like the data is available for us to look at, get a hold of. What is strange to me is how people can have such a long-standing misimpression of how we do end up in this place. So, going back to Eisenhower and the smoking, feel like if either one of us was blasted back in time, we'd be like, "Hey! Hey, guys! >> [laughter] >> You're not paying enough attention to the smoking." Yeah. The smoking, huge deal. And while we can't say with complete certainty that this is exactly why Eisenhower had the heart attack, we can't say it with enormous confidence. Right. So, by the same token, if heaven forbid, if one of my friends that I'm describing, who's a challenge case, has a heart attack in spite of how confident they feel right now and how low they've gotten their LDL cholesterol, I don't want to be the friend that goes, "I told you so." I, I want to be the caring individual that's in their life that got them to just get the data that I'm bringing to their attention. Right? But, yeah, after I've had times where I've witnessed first-hand visiting people in the hospital following bypass, I've, I've been present when people are intubated. It's all, again, it's another thing that Hollywood kind of has a very kind version of it. And let me tell you, until you've gone through that, you don't know why people get DNRs. >> [laughter] >> Um, it is very serious. Having to go and get your heart operated on, and exactly what you said, you will never be the same after that. You, it's a major surgery. As routine as this might get, as, as good as the survival rates may have improved to, you got to care about your ticker. You just got to. Yeah. You, you really need to keep from getting into that state. And so, I, that's, that's why your book title is great. It's a great book title. Stay off my operating table. That's, that's the message. >> You'd like to just turn off the lights and be like, "Ah, >> [sighs] >> no customers anymore. What am I going to do?" >> Yeah, exactly. I hope we get there.

Six or eight hours without a bathroom break, you do surgeries for that long of time. Is that right? >> Yeah, it's not the routine, but sometimes it ends up that long. Do you just, there's got to be a strategy to that, right? Like, do you, do you chug well beforehand and then make sure you do enough bathroom breaks right before you go into operating? Is that how that works?

Um, you know, I think it's kind of a learned behavior. Uh, I, I wish I could say I was that strategic. Uh, this is one of the interesting things though about contrasting my life as a heart surgeon before low-carb versus after low-carb. Uh, the ability to deal with all of that stuff, right? You know, the hunger, right? You know, that I used to, right? Have. It was a very real concern, right? I'm going into the operating room for, you know, four to six hours, you know, what am I going to eat before? What, what am I going to eat after? You know, being hungry uh, in the operating room, right? Versus now, I mean, it just like, yeah, when you're fat adapted, it's no problem, right? I routinely fast 16 hours a day, you know, so, you know, no big deal. And I, I, it's a very real difference, you know, the, the mental sharpness, the mental acuity that people talk about with this. You know, I am in a profession where that has a very real difference. Probably, you know, there, there are probably some examples that I could go back to that, you know, maybe that made the difference between the patient, you know, coming out of that operation well versus not well. And I now, you know, and again, contrasting my 25-30 year old self who was pre-diabetic and morbidly obese, but 20 years younger than I am today, and I truly do feel I can perform better in the operating room today, you know, than I did 20 years ago with those long operations, with those, you know, difficult circumstances. So, it's just another example of the power of being healthy, metabolically healthy, that I see the impact of every day. I look back, gosh, now it's what, 20 years practically. I look back to my wedding pictures. My wedding pictures, you can tell I'm younger, but I'm also just heavier. Yeah. And same thing, I just am happier, healthier. It sounds, it sounds self-evident, but I often make this as part of my pitch to other people. You know, you, there's a spectrum when it comes to low carb, but just getting lower carb, if, again, part of your problem is a carbohydrate intolerance, is something worth considering, because you may not realize just how much being feeling better becomes its own incentive. It, again, it may sound self-evident, but it really isn't until you've gone there. A lot of times what I'm trying to do is I'm, I'm trying to talk people into just giving it a, just giving it a phase or, you know, a trial period. Often 30 days. I just pitched the 30. You could do anything for 30 days. Do this for 30 days. You could eat whatever you want on the 31st day. Let's get blood work at the beginning through, yeah, through, through OwnYourLabs. Let's get blood work at the beginning, get blood work at the end. And do the comparison of the blood work. And a lot of times what friends of mine will say is, well, I can't get my triglycerides down, you know, I just, it just is what it is. I think it's a, a genetic disease or something. I'm like, give me like a little bit of time. Let's find out.

One of the things I like about low carb, getting back to one of the challenges with processed foods, or at least a lot of types of processed foods, is that if you're eating whole low carb foods, it's difficult to overconsume them. So, if you're having, you know, a big steak, it's very hard to overconsume a big steak. Try it. No, for an eating contest with somebody else trying to eat a lot of steak, it's very difficult to overconsume a big steak. And if you did have a very large steak, it probably will last you for like another, you know, 16 hours, 20 hours or something. That actually happened to me once. I really wanted to, it was one of the most delicious steaks ever, and it was really expensive, and I tried just genuinely tried to eat as much as I could. Spoiler alert, I didn't, I didn't succeed eating all of it. But I ate so much that I didn't want to eat for 24 hours. Spontaneously. Yeah. No, that, it's a very real effect. And you know, it's interesting. I, as a clinician, you know, sort of struggle a little bit, right? Cuz yeah, I love getting all the labs, right? And I love doing that deep dive and showing the patients, you know, this factor and this factor. But in the end, the most powerful thing is just eat like this for 30 days and see how you feel. And really, I think that's what keeps more people doing it, right? You know, the reality is is that most people don't walk around every day thinking about their triglycerides or thinking about their A1C even. They're thinking about how they feel as they go throughout the day, and the difference between how they feel when they're metabolically healthy versus when they're not metabolically healthy becomes the most powerful, you know, selling point of this approach ultimately. And it's what people generally, you know, keeps them sticking to it, cuz um, I think what happens often is people, right? You say, go do this for 30 days. And they're very enthusiastic, and they're motivated, and they do it, and they're like, I feel great. And they're like, I'm going to keep doing it, right? And then they hit a point where it becomes sort of the routine, and you know what happens is we then sort of stop thinking about it, and so we slide back to old habits. Um, but then they notice even more, right? How bad they feel. And again, this was something I experienced, right? You know, going through my life, you know, before I went low carb, I don't think I fully realized how bad I actually felt. Like, you know, you kind of, I went through my days, and yeah, you know, I would get pretty tired in the afternoon and have to have a bunch of coffee, or I'd go take a nap in my office after surgery, right? But this is just normal, right? And things hurt when I got up in the morning, and you know, all of this stuff that we think is normal.

>> And we, we can't stress enough that why you think it's normal is you have a whole bunch of colleagues. Yeah, everyone else is in the same state. Exactly, exactly. Everyone else is unhealthy around you. And the most powerful thing, right? When I, you know, did low carb the first time, I'm like, I feel great, right? I'm not tired in the afternoon anymore, right? And this is even before like the big weight loss or anything. You know, people notice those effects much earlier. And then, you know, when I did have those slides back, right? You know, and it's like, oh, I really feel like crap now. >> [laughter] >> You know, it's interesting. This is another sort of thing that goes on, you know, within the community, right? And everyone's like, well, you know, if you only can feel good when you're on a low carb diet, right? And you can't tolerate this other stuff, right? Are you really healthy? Right? People will kind of have this argument that like, I've never understood that one. Yeah, no, neither do I, right? That's exactly what I'm getting at. I'm like, this is the signal from your body like you shouldn't be eating this other stuff, right? And people will make this argument like, well, but if you can't tolerate eating that other stuff without feeling like crap, there must be something wrong with you. And it's like, no, this is like how human beings are like actually supposed to exist.

>> This is, by the way, asymmetrical with medicine, because often these, often I hear these arguments frankly from doctors, which makes it worse to me. If the doctors themselves are fans of, understandably, medication that makes patients feel better. >> [laughter] >> And you're like, cuz if somebody said, oh, well, you clearly have a problem if you need this medication to feel better. The doctors would be like, wait a sec, if it does work for that patient, it's efficacious. Why are you trying to discourage the patient from being on this medication? Well, by the same token, if you get into a state for which the ketogenic diet or even just a low carb diet, you find to be beneficial, and you're like, ah, I do miss being able to have my hot fudge sundaes, but that's all right. I feel better being on this diet. And then somebody's coming in from the side door and going, it must not be that good though, because you seem to need to be on it in order to feel better. Who cares? I know. I, yeah, it's the, it's again like logic that I don't get. But as I was saying, like that is what I think really keeps people on it, you know, all of the labs and the scans and stuff, you know, they're interesting, but more and more people come back to I just feel better, so why would I stop doing this?

Why we never got into why you decided to go low carb. What, what was the catalyst? So, my journey into low carb, so I was, you know, I was overweight, morbidly obese actually. I was pre-diabetic. And but I didn't realize low carb was an option, right? I was in that camp. I had literally never really heard people talk about low carb diets, right? I knew eat less, move more. And I had done that a bunch of times. You'll appreciate. So, I was a, I was in the last year of my surgical residency, and I decided, you know, I needed to lose weight, right? You know, again. This was right when the Palm Pilot had come out, and I got, you know, the, I don't even think we called it apps, you know, but I had something on my Palm Pilot that I could track my caloric intake, right? So, I started doing that, right? And I set my calorie limit, and I made an effort to go to the gym as much as possible, and, you know, lost a bunch of weight. And lo and behold, like so often times happens, within a year I had gained back the weight and more. Um, so, you know, I had lost weight a bunch of times in my life, but here I am. Uh, so, I was uh, what now? Early 40s, you know, a couple of young kids. Um, my wife uh, after having our children was struggling with heartburn and, you know, a bunch of other sort of, you know, things and happened to see a um, it was actually an acupuncturist that she was seeing just for, you know, musculoskeletal, whatever type stuff and said, "You know, you really should try cutting out gluten." And uh, she comes home to me and she said, "You know, I saw the doctor and said, you know, I should cut out gluten." And me being the heart surgeon I am said, "Well, that's pretty ridiculous. You [laughter] don't have celiac disease. Like, why would you cut out gluten?" You know? And she said, "No, I think I want to try cutting out gluten." So, I said, "Okay, well, you know, I'm a supportive husband, you know, we'll try cutting out gluten for, you know, a little bit." And this is uh, right, this is probably 2013 or so. Uh, so, cutting out gluten meant unintentionally going low carb cuz they didn't have all the gluten-free stuff, right? We stopped eating bread, we stopped eating pasta, basically. And uh, you know, probably after a week I was like, "Hm, I feel better." Right? [laughter] You know, the, the ti-, the energy was really the first thing I noticed. Right. So, I said, "Well, this is interesting." And um, again, I didn't really think about it, right? I just was we were gluten-free now. Uh, so, a couple of months later uh, I am at a meeting uh, heart surgeons meeting, the Society of Thoracic Surgeons. And there is a guest speaker who's on the agenda, some journalist by the name of Gary Taubes. Oh. You were literally there. I was literally there and um, uh, so, I'm looking through the program and I'm like, "Why is there some like journalist talking to us? Like, what is the" And I forget the exact name of the talk, but he had just written The Case Against Sugar, right? So, it was something about low sugar. And you know, it was one of those situations you've been to the conferences, right? There's like 3,000 people and you're like, "This session doesn't look that great. Maybe I can go back to the room and, you know, take a nap or, you know, go swim in the pool." But for whatever reason, I stuck around for the, you know, for his talk. And uh, Gary being Gary, you know, gives a great talk. And I was like, "Hm, sugar. Why haven't I like heard of, you know, like, why is this the first time I'm ever like hearing about a low sugar, you know, low carb thing?" And I said, "You know, I already cut out gluten. I'm sort of already there. You know, maybe I'll give this a try." Right? And I bought his book and I read the book like on the plane home and then I read, you know, Good Calories, Bad Calories. And that's when I first said, "Okay, I'm low carb now. I'm going to go low carb." And um, you know, I again continued to feel great, lost all the weight. Uh, and now I was able actually to keep doing this, right? I'm like six months in, I'm a year in, right? And I'm like, "This is great." Uh, and that's right about the time that I started, you know, getting on the internet and looking at low carb stuff and, you know, started coming across some different things. Uh, I ended up going uh, and I think this is where we may have first met, Nadir Ali hosted a conference and I said, "Oh, maybe I'll go check this out." Yeah. And um, and that's, you know, haven't looked back since.

Yeah, I remember I'd already seen you uh present before, I think in another video, something along those lines. And there's sort of, there was sort of just a kind of a broader expansion on the medical side of the fence with low carb doctors who were both pro metabolic health and somewhat skeptical with regard to cholesterol in particular. And Nadir Ali was certainly one, you were emerging. Yeah. Um, and we haven't gotten to it yet, but you also launched a podcast ultimately. Right? So, you're also a podcaster yourself. >> Yeah. But that came a bit later. Am I, am I not mistaken? Yeah, so the sequence of events for me was uh, so, I went to a few conferences. Um, you know, I was actually at uh, Low Carb Boca. And uh, you know, still a practicing heart surgeon. And uh, I ended up uh, I think Tro was the first one I had this conversation with. And uh, you know, I kind of went up to Tro, right? And I was like, "Oh, I've been listening to your podcast, you know, finding all of this very interesting." And he's like, "What do you do?" And I said, "I'm a heart surgeon." And he was like, "And you're here?" I'm like, "Yeah, [laughter] you know, this is all." He's like, "Well, why are you in the audience? Like, you need to be up, you know, talking and all this stuff." And uh, again, I, I wasn't really. So, I was like, you know, I, I've been thinking about like, cuz at by this point I had, you know, friends and family, right? That I had told about this and they had followed it and they were having good, you know, And I was like, "Well, yeah, I was start kind of thinking about starting a little practice, you know, just an on the side thing where I'll help some people." I'm like, "How do I do that?" Right? Cuz I had been a employed heart surgeon my entire life, right? I didn't have my own, I didn't run a practice, right? I just worked a hospital and, you know, they did all that. And I'm like, "Well, you know, how would I go about doing that?" And, you know, Tro was great and he said, "You know, go this software, this software." You know, he's like, "You can do it online. You can just see people." And he kind of helped me get started. So, I started the practice and then uh, shortly after that was when I had met this ghostwriter and he said, "Why don't you write a book?" You know, and he's like, "It will get the message out there. It's a way to kind of help promote the practice." So, I said, "Sure." So, we did that. Uh, and then uh, what happened was, you know, so to promote the book, I started going on a bunch of other people's podcasts. And then uh, I had another friend who said, "You know, why don't you start your own podcast?" And he's a uh, he does podcast production. He's like, "I'll help you out." So, I said, "Great. Sounds good. What do we do?" This is a good one. So, he said, "You know, why don't you just talk about what's in the book?" He's like, "Just go start talking about what's in the book." Right? So, I said, "Sounds good." So, I sit down to like try and record my first podcast, right? And I'm talking about a little bit that's in the book and I talked for maybe like half an hour or so and I send it to him and he's like, "This sucks." He's like, [laughter] "You can't do your own podcast." He's like, "How about I interview you about what's in the book?" And he's like, you know, there's 12 chapters in the book, we'll do 12 episodes, right? We'll just do, you know, chapter by chapter, I'll interview you and talk about it. And we did that. And that worked a lot better. You know, uh, and then he said, you know, then we got to the end of that and he's like, "What else do you want to talk about?" And we came up with a few other topics and then he's like, "Maybe we should start, you know, like, bring on guests, you know, all these friends you have, you know, in this community." And so, we started doing that. Uh, we just released episode 250. Uh, we've been doing it for five years now and um, yeah, you know, as you know, podcast uh, very few make it past episode 10. Uh, I think is the stat, right? >> [laughter] >> And uh, so, yeah, so that, so that happened and, you know, as the podcast grew, the social media grew, all of that. And uh, here we are today.

I almost started a podcast at least three times, maybe four. And all those times it was trying to figure out the right timing, what it was going to be called. But I kept uh, I kept seeing Joe Rogan. And granted, Joe Rogan is who he is, so he could just, you know, people would show up. He's largest podcaster in the world. But, but I wasn't so much just, you know, jealous of his level of influence and the money and all that sort of stuff. Hats off to his level of success. It really was just this format. This format to me just has always made perfect sense. You just don't get the same kind of experience through a Zoom call. And that's the problem. The problem is, okay, but convenience level. That's easy. You know, just make sure the schedules line up. And you and any number of other guests from wherever they're at in the world, likely they already now have a good camera, they've got a good mic, and etc. Whereas, having like a physically dependent location for a podcast is kind of a big ask. But um, more and more, I just, I kept thinking, maybe the reason I'm never starting this podcast is because I, I'm not going to be satisfied with anything but this. Like that's just the bottom line. So, either I'm going to start a podcast or I'm not, but if I do, why not just give it the best shot I can? And so, um, as it happens, uh, they're not normally in the studio, but Madison is in the studio with us, the sound engineer who's normally on virtually, by the way. But um, helped to design all of this, this podcast studio. And uh, >> [sighs] >> I love it. Yeah. Yeah, I, I agree. Even though I do my podcast by Zoom because of the convenience and I'm rarely in one place, uh, I, you know, my dream is one day my podcast will get to this and being in person, it is just a whole different experience and um, you know, the podcast.

That I've had that I've been on, you know, that are set up like this, uh I think the impact is much greater and the conversation is just.

Yeah, it's a better. It's just a better experience for me and the guest. Uh it's clearly it's clearly going well out there because our podcast has grown like at the time that we're recording this, I think we're at 155,000 subscribers. And we're like 5 months old.

Yeah. And we're like on 22 episodes, I want to say. With a footnote. We have an important footnote. And in fact, it developed again last week. So, episode 10, as of this recording, episode 10 is not on YouTube. It's on Spotify, but it's not on YouTube. The reason why is the guest and I were chatting. It's uh Peter Ballstedt is the guest. We were chatting on a topic I'm afraid to even say the word out loud because what happened was the um podcast was basically getting suppressed by YouTube. And I got a label on it and so forth and I it was like, wait a second, it's not it's not a bad episode. Like I've seen plenty of things on YouTube where I would say, wait, this subject matter covered by this other person got a lot saucier. I thought it was actually a very disciplined, scientific discussion. And I didn't think his position on the topic of interest was extreme at all. I thought it was actually very moderate.

But, um this is where we had kind of got tested for the first time because not only were the numbers way, way, way down. I mean, I'm talking like if I'm talking the podcast before his was in the tens of thousands. And then all of a sudden, his was under 1,000 and was just like, you know, barely there at all. But on top of that, all of the other podcast episodes, which were accumulating views on their own, all flatlined. And I was like, oh my goodness, what the heck? Uh well, we'll just release the next episode. We get We're just going to have to stick it out. I released the next episode, it's flatlining. And I'm pretty confident at that point it's because of episode 10. So, I reach out to Peter and Peter was great about it. I said, I've talked to some other engineers in the industry. They say, really, your best move is to straight delete it from the channel. You can't even just take it private. You need to just delete it. I don't know how accurate what they were saying was was, but sure enough, once I deleted it, it's like it lifted the curse.

Yeah. And I past that point, I was like, well, that subject probably won't come up again. So, it's not going to be that big of a deal. Last week, we released one with Jenny Eclair Mitich. You know who she is?

Mhm. She's great, by the way. Oh, yeah. Awesome person.

That episode we released, same thing. All of a sudden, a flatline and all of a sudden, it extends to the rest of the channel. Uh We tried playing around with maybe the description had certain keywords in it or something, so we had a real milktoast version and literally relaunched it a second time. Still had problems. So, I bring this up because this is one of the downsides of having physical, you know, podcasting, where now I need to be mindful of what I think might trigger the the algorithm to be upset with us, right?

Yeah. And that part I don't love. But, I plan to diversify. Even though YouTube's kind of where we're focusing, it you know, means that we need to put a little bit more effort into Spotify and Apple Music and so forth, the other places where podcasts could be. But, I don't know, we may also try some of the other platforms just to, you know, keep it in as many as we can.

Yeah. Yeah, and again, it's I think something unfortunate within our environment these days, right? That these topics, you know, can't be discussed, right? And you know, again, I mean, and you sort of go back to cholesterol as as one of the earlier examples of this, right? That, you know, it it became an unquestionable truth, right? You know, and even when I think back, right? So, I was in medical school from 1994 to 1998. Um Statins were kind of a new thing, right? You know, they were By that time, I guess they had kind of established their place in the market, right? But it certainly wasn't to the level that it is today around cholesterol lowering. But, cholesterol lowering, you know, as the treatment for heart disease was an absolute truth, right? I never heard about uh Dr. Yutkin, you know? I never heard about Dr. Kraft's work on, you know, heart disease. Um it was unquestionable that cholesterol was the cause of heart disease and that if we want to manage heart disease, it has to be, you know, just lower the cholesterol. Uh and you know, it it I think back, right? If I had like kind of raised my hand back then, right? I I think well, I mean, Nick Norwitz is a great example of this now, right? Cuz he went through medical school, you know, knowing this already, right? And was able to question it. And if I think back, like if I was Nick back then and I had kind of known that, you know, these holes in the cholesterol argument and tried to raise them with my mentors, you know, with the professors and all of that, uh like I said, it was an unquestionable truth. You you cannot question that. And it's only now, right? I I don't think uh your work, for instance, right? Would have made any headway, you know?

Yes. 30 years ago. No, and and this is part of why we're doing the documentary. Yeah. Like you establish the science over here. Okay. In in a sane world, we're like, hey, we're published. Hey, here's the data. There you go. Scientific community, do you want to propagate this? And we know they'll go, uh Well, there's already this wealth of evidence that's over here that we think is more, you know, established. So, yeah, I wouldn't expect it to be taught to you. I Yutkin predates us Yeah. by a I don't know. It's It's It was a century ago. Am I remembering this correctly? Yutkin Uh no, he was around you know, yeah, he was 1940s, 1950s, you know, about the same time that Ansel Keys was 80 years ago.

Yeah. And here we are in a diabetic pandemic. Yeah. Right? And you have to have Gary Taubes write this book that you saw on The Case Against Sugar, right?

[laughter]

But that's where we're at. So, yeah, getting it back to um getting it back to censorship. If we are going to be, you and I, if we're going to be podcasters, if we're going to be content creators, yeah, we have to kind of be aware that it can happen. But, this new paradigm that we're in, I mean, it's exciting in many ways because we no longer are beholden to some distributor to get the word out, to get content out. The catch is that as is the situation, there's not distinct, well-defined laws. There's not a clear and clean adjudication process. There's just these community standards, which is some amorphous.

Yeah. Opaque, you know, you'll know if you get stopped. And if you get stopped, maybe you can do something about it. Probably you should just delete it yourself. And hope that the almighty algorithm takes pity on you and doesn't uh and let you continue to post new episodes.

Yeah, and there's the challenge of, you know, again, trying to get we'll call it these sort of minority reports out there, right? When we're dealing with an overwhelming majority of data that points one direction. And this is again getting back more to the cholesterol topic. We have this overwhelming majority of data that points one direction and that is believed to uh prove it, right? Even though there is a minority of data that starts to poke the holes in that argument, right? And again, a good scientific discussion is supposed to consider both of those, but overwhelmingly what we see today is just, you know, it it's got to be true because all of this all of these um people say it's true. We'll call it you know, all of these there are you know, however many thousands and thousands of papers, right? That support the lipid hypothesis. And the fact that there are a few that you know, contradict it or poke holes in it, right? That doesn't mean that it's not true in medical world, right? And this is what I find so fascinating, right? About talking with you as an engineer because in engineering world, right? The black swans, they're the whole story, right? They prove that the rule isn't true. Uh but in medicine, we kind of just ignore that, right? And say, well, you know, all swans are still white even though there are some black swans over there. Those are anomalies. Those are outliers, right? You know, It's frustrating when a word like paradox is introduced as just kind of a way to hand wave. Be like, yeah, the paradox of the black swans, but all swans are white. Wait, you can't say all swans are white since there are blacks. Well, again, I already acknowledge the paradox.

Yeah. Right? It's a way of saying miscellaneous. But but to to this larger topic of cholesterol, I'm I'm coming in from the outside before I was publishing anything. I'm doing searches. I'm seeing that indeed there are all these things that seem to support it. The me of today knows now what the me of then didn't realize, which is that there is a direction the wind is blowing. There was an undergrad I talked to. I want to say literally 2 years into this and I was trying to talk them into more uh research with lean mass hyper responders. It was shortly after I designated the phenotype and uh he was very interested and he said, yeah, but I can't I mean, I can't like actually do this at this stage in my career. I was like, it's the perfect stage in your career. You're like, you're budding, you're new, you know, help me to get some of these labs, you know, interested in this topic. He goes, no, I think I think that they will believe it's only going to likely hurt the lipid hypothesis. And I and I'm naive me, I'm going, what's the prevailing hypothesis, right? Like that's isn't paradigm shattering like the basis of science? Like don't you want to find a discovery that rewrites the things you know? And he was very candid with me and it was like, no, I needed to be doing the opposite. I need to be building on my resume. And he he called this a resume He called this a resume building paper he was working on it right now. Resume building paper, his words with regard to something that was supportive of the lipid hypothesis. Because the more that you're kind of establishing that you're, you know, in the right way, especially if you can bring novel insights that are in support of this like larger structural hypothesis fulfilled the whole field is built on.

Yeah. Filled.

[laughter]

The whole field. Then you're you're part of the wind. You're going with the wind in the direction that it's going, right? And I don't bring this up to suggest that there's this uh there's this, you know, conspiracy of a bunch of these kingmakers, you know, meeting in the dark room every morning to to get us all going on statins. It's not so much that it's a conspiracy. I do think it's an ecosystem. I do think there's a broader awareness of what the expectations are that has a feedback loop in and of itself. So that when something pops up and it's like, this doesn't this is not supporting the the broader hypothesis, there's sort of a a natural almost knee-jerk level of disbelief because that can't be right.

E Yeah, this is a very real uh thing, right? For most practicing doctors. Um the the realization that I had to come to, right? That the disease that I had dedicated my career to uh fighting um was not what I was told it was, right? That's a massive shift. Uh and you know, and you can take it a step further, right? And you know, and this part I might be a little bit more insulated from as a surgeon, right? Because admittedly as a surgeon, you know, I had short episodes of care with patients, right? I did their surgery. I got them through the post-operative period. Um and yeah, I might say things like, yeah, you should continue on your statin or you should, you know, think about a low-fat diet, right? Um but you know, when you as a physician have to admit, right? That that was wrong advice. And then think about all these patients that you've maybe unintentionally harmed or at least didn't make them as good as you could have made them. We can say, you know, maybe more would be a better way to say it, right? But if you're a doctor who's gone through your career, right? If you're a cardiologist, if you're a lipidologist, right? Who has gone through your career and this is essentially the only thing you tell patients and it's wrong, right? That's a pretty massive, you know, thing that you have to contend with as a physician.

That's That's what That's one of the stories that I've discussed on here and I plan to talk about in the book is there's a doctor who had genuine I genuinely think it's a great doctor. I mean, really kind-hearted and he conceded this to me. He said, you know, I actually the more This is after multiple great conversations. He said, the more that I've chatted with you, the more I think you might be right about this, but I got to be honest, I'm kind of rooting for you to be wrong. Because the cholesterol lowering was always a big win. It always felt like a big win with him and his patients. And it's it's another place where I feel like maybe it's a different inherent attitude with us engineers that oh, you were giving me wrong advice, but it was based on what you already understood by that point in time. Okay. You know, that's fine. Thank you for letting me know. My bigger gripe in general, but particularly when it comes to science is a lack of course correction. To err is human.

Yeah, right? That's fine. If you do have a lot of accumulating data that should, you know, inform a new opinion, I really want that to happen. Not just for you, but for all of us, right? It's There's There's no reason to feel a level of buy-in with whatever your worldview is that the contrarian data that keeps coming up that's challenging it is not something that you can incorporate.

Yeah, and you know, that's how the monumental shifts happen, right? You know, and again, we can see so many examples of this, right? I think about, you know, driving, right? And I think about, okay, you know, we spent all of these many, many years, right? Thinking about how we make driving safer, right? We make the cars better and we put airbags in and you know, all of the safety systems, right? That are in the car. And then, you know, Elon Musk comes along and says, well, what if the cars just drove themselves, right? And can do it, you know, orders of magnitude better than humans can. And you know, and of course when he first started saying this, everyone thought, well, that's crazy, you know, you can never do that. And here we are where I think it's becoming apparent that it's going to be true, that it maybe is true and now it's just a matter of getting everyone to accept, right? That, you know, this is the way of the future. And you know, the really big things that happen in medicine, again, going back to, you know, John Gibbon thinking he can, you know, design a machine that will take over the function of the heart and the lungs so that we can, you know, save all these patients' lives and operate on it, right? And you know, I'm sure everyone around him said, you're insane, right? And you know, 20, 30 years in the lab trying to do this, right? And all of the failures, but it's only when people take those big leaps that we get these, you know, monumental shifts. And I think, you know, really heart disease is at that inflection point. We can keep going down the same pathway and maybe we can make it incrementally better, right? With here's the new medication and you know, this and that. Or we can step back and say, we've been doing this experiment now for 70 years. The results have been quite disappointing. Maybe we should change shifts. Maybe we should change focus, right? Shift our focus and maybe we can have monumental impacts, right? I talk about how my dream is that heart disease will no longer be the number one killer. Right? We've been doing this for 70 years. It's still the number one killer, right? We're really not gaining any ground. Uh we should be able to really think bigger and say, you know, we can make heart disease not the number one killer anymore. And I think that, you know, metabolic health, insulin resistance, right? Is the way to do that. Uh and okay, we'll start looking at some of the other tools, you know, uh maybe it's not all about our diet. Um I think our diet is a big part of it, right? But I can also see now, okay, we have these GLP-1 medications that help with insulin resistance. So, maybe these are tool that we think about how we integrate into, you know, what we're doing. Um but the first thing we need to do is we need to change that focus, right? And again, you and I have discussed, right? The evidence that we have that the magnitude of effect from insulin resistance on heart disease specifically.

So, not even close. so not even close to uh cholesterol. So, let's just start focusing on that. And uh again, I'm optimistic that maybe we're starting to see the conversation shift that way. Um when I do talk to my colleagues and I say, okay, cholesterol is cholesterol. What about insulin resistance, right? And it's really not that hard to like, okay, you're sending off the cholesterol panel. How about you send a fasting insulin level as well, right?

Yes. Oh my god. Uh or maybe, you know, what? You're your uh you know, you're a cutting-edge lipidologist, right? So, you've gotten that advanced lipid panel. And you're looking at the small particles. And how about saying, okay, if we could lower these small What is driving these small particles? It's insulin resistance. So, maybe if we fix that, the small particles that you're worried about, they go down, right? Maybe that's a good thing. Like, let's just start bringing this into the conversation. Uh and I think that's the way, you know, and no, I'm not expecting that, you know, the American Heart Association is going to have the big press conference and say, all that cholesterol stuff, we were wrong about.

[laughter]

Right? You know, That's not going to happen. But maybe 10 years from now, we find our place, right? Where, you know, those case presentations that are being done at the American Heart Association meetings that you were talking about or the Lipid Association meetings, right? They're all about how we fixed insulin resistance and not just focused on how we lowered the cholesterol.

I've wondered how much these GLP-1 agonists are kind of a forgive the term a gateway drug toward the broader recognition of metabolic health.

Yeah. Like that's that's what's fascinating is I think um everybody who I've chatted with for this podcast has mixed opinions. It's generally a net positive, especially for challenge cases. I can see this myself for my challenge cases in my life who they're saying, listen, I I need it in some form of a pill or, you know, an injectable in order for something to happen for me. Otherwise, cuz I'm just not going to give up my way of eating. I'm not going to give up my lifestyle. I'm just that's just who I am. From their perspective, that's that's what they would say. And for the for those folks, I'm like, well, I you know, I'm glad there's something that's new that you can For those who seem to want to make lifestyle changes, but to find that it's difficult, but that is in fact their core desire. I hope, and I've said this to them, I hope that it's a jump start. Um Dr. Boz, who I'll also have on here, too, she's got a great program where they do microdosing.

Mhm. Because it can be argued that the dosage is too high. Yeah. And that there's a lot of downstream negative side effects for how high a dose people are taking. Um that sounds attractive to me for them, for these people I'm talking about, but ultimately, the the key component is for there to just be um an awareness that metabolic health improvement, even if it came through a pill, might demonstrate an outcome of relevance, so that at least it lives in hard data of what's in the peripheral view.

[laughter]

Cuz how can I get your colleagues to see metabolic health? How can you get your colleagues to see metabolic health and its distinct relevance, not just on all-cause mortality, but on cardiovascular disease? Ah, we put it in a a form that's a medication, and now now you can actually see efficacy, and you can see outcome data. Then it's sort of like, hey, now let's talk about what if we didn't have the pill or the injectable, and you could talk people into the same outcome that you'd get from these GLP-1 agonists in that fashion. How great would that be?

Yeah. No, I I think that's exactly how I think about it, and uh you know, we Yeah, we're using them as well, and um you know, oftentimes I I agree with Dr. Boz with the net on this, you know, the the problem is the dose, and the problem is the strategy, right? That this is the only part of the solution versus this is a tool while we're doing this other part of the solution to help you implement it and to augment its effectiveness. And um I think it is a gateway. Uh and you know, that's why I am uh enthusiastic about them because it's bringing it into the conversation. Uh again, I don't agree with the majority of the way that it's used out in the standard medical practice, you know, that this is just the solution to the problem. Uh but I think it can be a very useful tool, and I think it does open up that conversation of, okay, we've now demonstrated that these things reduce cardiovascular risk. They don't reduce cholesterol, so how are they doing that?

[laughter]

Oh, you know, there's this thing called insulin resistance, right? That they they act upon uh that's reducing cardiovascular disease. What are some other ways that we might be able to reduce insulin resistance? I think that's more and more how that conversation's going to go, and uh I think it's going to ultimately lead us to a better place. Um like I said, it's not the total solution. It's not going to get the cholesterol out of, you know, out of the discussion. And again, you know, you and I agree, right? Cholesterol isn't meaningless, right? We do need to talk about cholesterol. Um we just the way that I view it is we don't talk about it in the right way, you know?

That's that I would agree.

About the quality of your cholesterol more so than the quantity of your cholesterol and the environment that the cholesterol is in.

Yeah. I So So, we'll we'll drop in there for a little bit of nuance here. There's I tend to find that um if I'm speaking to a regular lipidologist, then it's apoB apoB apoB. So, the number of apoB particle apoB-containing lipoproteins is going to be the most relevant component toward the progression of atherosclerosis. Uh this is part of what our study is providing a lot of value for because it that that rather that relatively simplistic version of the lipid hypothesis would suggest that lean mass hyper-responders are a high-risk group by by definition. Full stop. This is where our data is going to be very valuable because not only is it testing that, but it's also seeing how much there's an association. And spoiler alert, as of right now, our data is pretty strongly showing that no, there's no association. If I'm talking to a low-carber circa you know, 2016, 2017, and so forth, it's about the small dense versus the big fluffy. You alluded to something that I myself would have would have double-clicked into, which is, wait a sec. How do you end up with the higher preponderance of small dense LDL particles? Metabolic health is directly associative to that higher proportion of small dense LDL particles. Let me state this a different way. If I give you poor metabolic health, you will have a change in your lipid profile. Your lipid profile will change. Now, this is the definition of a confounder, right? If a thing, such as your insulin resistance, actually affects two other things, your lipid profile on one end, and your cardiovascular disease risk on another, it's difficult for us to then disentangle what the relationship is between these two. So, your lipids and your cardiovascular disease risk, having this confounder in place, make it difficult to come back to the thing we were talking about earlier with things like adjustments.

Yeah. How can you make an adjustment unless you get these two away from this, right? Okay. So, now we get back to the quality of the cholesterol, the way that you described it. So, you might be I think what you mean by that is the quality of the particles themselves. So, for example, this gets away from apoB, this gets away from small dense versus big fluffy, there's now modified LDL particles such as oxidized LDL or glycated, some way in which it's modified, right? For which there are a number of people in low-carb space who are focused on that, oxLDL. I'm interested, for example, in something called uh uh phospholipid apoB. Um now, what do I want to say? Oxphospholipid apoB is what I want to say, yes.

Yeah. Also very fascinating, very interesting, but at the end of the day, my position is not so much that I'm going to express confidence this is exactly the way it is, so much as I'm going to say I want to put on the table that all versions of the lipid profile and its association to cardiovascular disease may be predominantly about the state of the body and the impairment or dysfunction related to the lipid metabolism as to why there's that association between it and the uh development of atherosclerosis. That's thing one. Thing two is, is there a part of the causal pathway apoB lipoproteins and atherosclerosis? Yes. Can both of these things that I just mentioned be true at the same time? 100% they can both be true at the same time. You can have a systemic problem inside your body that again both changes your lipid profile and is an independent risk for cardiovascular disease, and we already know this from say the work of Brown and Goldstein. Children with homozygous FH, if they bring their LDL levels way down, are they still at a greater independent risk compared to other people of the same LDL levels? We already know they are.

Mhm. We know that. Now, I want to be fair, a lipidologist would say, "Well, there's maybe more things with regard to how they're developing when they're very young or something like that." It's possible. But right now homozygous FH is incorporated into these meta-analyses like the famous 2017, you know, consensus paper. Making the case that no, it is the LDL, it is the apoB, that's how it's presented to us. That is what distinguishes them. It's not these additional factors that are brought in later as an explanation as to why there was that independent risk factor. So, all roads in my mind lead back to lean mass hyper-responders. We had to get a population that didn't just have elevated LDL, but like many in our study have sky-high levels of LDL. We have six people with an LDL of 400 or higher, right? So, their LDL, their apoB, and Philip, small dense LDL particle absolute numbers can actually be higher in these folks, the absolute numbers, even if the proportion is smaller. Right. So, if we're going by absolute numbers, which would be you know, per the lipid hypothesis, their absolute number of small dense LDL particles would be higher. You would then think that this would show itself through the development of plaque. You would think that there would be an association. But do we see that? So far, the answer to that question is no. Across four analyses, our study has four analyses.

I'm waiting for you to publish that piece of it, but yeah, no, and and again, I think the and again, there's literature already to support this, right? The proportion of small dense versus the number of small dense. Yes. You know, difference there. And and that's really what I, you know, now talk to patients about being your cholesterol quality.

And it's,

[snorts]

you know, it's challenging, right? Cuz you get the lab report and, you know, it's the red number, right? For the small dense, right? And the apoB, and all these things are red, and, you know, here I am trying to explain to them, but, you know, it probably shouldn't be red because of this, right? And and again, it's not something I made up, it's in the literature, right? The proportion of small dense LDL is more predictive, right? And again, associational, yes, and maybe there are some interesting populations that we could look for at that help us, right? Along the same lines of the lean mass hyper-responders, but the proportion of small dense LDL as, you know, of your total particle count is a greater predictor than the number of small dense particles. Right. Um and, you know, again

But that's a that's a huge deal. But what you're saying right now is already at odds with the present lipid hypothesis.

Most lipidologists would say, "No, that can't be true." Right. They would say, "Listen, if you know the count of the apoB, you know the likelihood of the development of plaque." And the bottom line is if that's true, that would be showing up in our study. Yeah. Particularly if we, as I'm hoping, will get the 5-year scans. We'll see about that. It may end up having to get pushed to 6-year scans. We'll find out. Hopefully I can preserve the sample size. You know, I'll I'll take a moment. This is the benefit, Philip, of us being in person. I'll take a moment to say what I can say at this moment in time with regard to our study. Uh we're recording this um mid-February. I'll just mention that real quick. Hopefully by the time that I'm publishing this, this will already be news that's out. If not, there'll be an edit point here.

[laughter]

I'm looking over at Mattis in this moment. Um Here's the deal. The deal is we got the CLEARLY data set. I don't know how much you've been following. If you've been following pretty closely.

Yeah. Yeah. So, we get the CLEARLY data set. A lot of this is already now pretty public, but it's anomalous. And it's only after I get the raw anonymized data do I find a number of things that were not identified before. And then a very lengthy back and forth is going on behind the scenes where I'm pressing them to do a fully blinded reanalysis of the data set. It later comes out that in fact it wasn't fully blinded. The initial pass, so we didn't ever even get the original initial fully blinded pass. We get a HeartFlow analysis, which is a competitor to CLEARLY, but that one's operationally blinded. And their the patterns of their data match what it was that I thought were problematic patterns that I identified to CLEARLY before we got HeartFlow. I'm totally speed running this, by the way. And then we finally get the pre-specified MedisQ Angio.

Mhm. You're already familiar with all of these.

Yep. In fact, you yourself are using one of them now. Yep. And this was one of the interesting things to come out of this for me is I don't know that I think that there is a problem with any of these four analyses, and that includes or sorry, I don't know that I think there's a problem with any of these four processes and how they conduct their analyses. I just know that the data set that was delivered to us itself from CLEARLY for our study has some very glaring anomalies in my opinion. The lawyers will want me to say in my opinion. But it took the accumulation of a lot of these other data sets for us to then further press behind the scenes for this to get resolved. Only after we did literally just about everything did we need to decide on this next major step. The next major step is in development now. I It's like I can't say it out loud, but you can probably tell what's coming. But I was quite adamant, you know, beyond beyond the fact that the detractors would understandably be concerned if it just looked like we were casting that data set aside, we needed to do our duest of due diligence before pressing further. Beyond the supporters wanting to get the data, there's there's me in particular, Philip. I feel like this is something that's due us.

[laughter]

I feel like Yeah. we ran we did everything we were told to do. What got received is I believe something that we can say, "Hey, all of our other teams would be willing to do a quality control check. Why are you guys not willing to do one, especially when this is unlike any other data set in all of imaging by far? Got a 24-point report on all these different issues. Two of them are already the easiest ones to communicate to a lay audience. You're probably already familiar with both of these by this point, but I'll just say them again. They're all progressors. There's not a single regressor, including at the lowest level of statistical noise. I don't know what that's about. And then the other one being that those with the CAC of zero had a severalfold higher increase in plaque than those with a positive CAC. Again, you being in the research, this is just highly implausible. So, at this moment in time, the reason this has taken as long as it has is because we did have to make a deliberate choice, and it was mainly my choice to make, which is do we exhaust every avenue to try to get this quality control check, including waiting until these other analyses are in because that would have, you know, apply a lot of pressure if indeed they all agreed with each other, which they do, and disagreed with this anomalous data set, to give at least every opportunity for this quality control check to happen. But, there's one piece of this I can't tell you about yet. And it's kind of the final bit that brought us to the point we are now to basically determine that the clearly analysis needs to go. And, um, that that's going to be coming in a future podcast. I may be able to talk with you more about it offline. Hopefully. Um, you know, but, uh, I guess, you know, my perspective, right, as a clinician, right, you know, knowing all this, hearing all this as it's going along, right? Is, you know, these are patients, right? These are people who are trying to make decisions on all sorts of aspects of what they're doing in life, right? Based on this imaging. So, it's important for us to know that the interpretation of the imaging is correct.

Yes. You know, of course. Um, and you know, and if there are different, um, if there are different interpretations, right? And this is something that I think patients maybe have a little bit of a hard time understanding. And And quite frankly, even a lot of clinicians, right? Would have a hard time, right? You get a set of pictures, a CT angiogram. They're there, right? They're physical pictures, you know, we can look at them. Um, how do you interpret those differently, right? Right? Where does this all this variation in how they're interpreted come from? Um, you know, I kind of understand it, you know, as a clinician, you know, uh, and again, it's something that I probably in the past wouldn't have really thought about, right? But, looking at it through this context, uh, it makes it apparent to me. And, you know, we as clinicians now need to struggle with, okay, well, which interpretation, or, you know, how do I, you know, again, how do I translate that back to this patient, right, who has a very real question. Is my disease getting worse, or is my disease not getting worse?

Right. Right, that's the first question we need to answer. And I feel like I feel like I can give a better answer today than I could before.

I I definitely think so. Yeah, so, you know, and maybe this leads into another part of our conversation, right? This this advance in imaging, right? When it comes to heart disease is just monumental.

Yeah. And, you know, you and I were at the low-carb conference, you know, a month or two ago, uh, where it was a focus, right? That okay, great, cholesterol is what it is. Insulin resistance is what it is, right? Inflammation. Um, but what matters in the end of the day is we have a very real disease that I look at in the operating room every day, right? And now, what I want to know is, okay, I have these patients who haven't made it to the operating room, you know, is their disease getting worse, or is it not? This is something very important that we should be tracking, right? And this is another thing that just, uh, quite frankly, astounds me these days that most cardiologists aren't interested in imaging the disease that we are trying to manage.

Yes. Like even something like a CAC scan, right, that again, you know, we in low-carb world think is everyone has them, right? The majority of patients have never had this scan, have never heard about this scan, don't know what it is, right? And, you know, they again, uh, are not looking at the actual disease. They're trying to look at all these surrogate things that may or may not predict your risk of the disease. Uh, and why don't we look at the disease more? Yes. So, I think that in and of itself, right, asking the question in the way that you did in the study, right? That's saying, okay, we have a disease that based on this risk factor, we think should be getting a lot worse, it should be getting worse quickly if we think this risk factor is what it is. So, let's look at that, right? And again, you're as far as I know, essentially the first trial that even looked at it, right? Did CT angiograms 1 year apart essentially to see if the disease gets worse with whatever factor we think is influencing that. Um, that maybe even more so than the particular aspect of, you know, what's going on with lean mass hyper-responders, right? I hope that there are a lot more trials coming out, you know, that flood great flood the literature showing me what happens in patients on PCSK9 inhibitors doing CT angiograms 1 year apart.

Yeah. It's All right. Let's Let's have fun with this because I rarely have a guest like you where I can really kind of unpack this. These These images, what probably a lot of people who who are not familiar with these DICOM scans, is when you hear image, you think of something that's 2D. You're probably thinking of something like a chest X-ray, and you think somebody like you is like putting up a heart, you know, X-ray. No, what these scans are is they're a series of images from multiple angles.

Yeah. And what's happening is it allows for a 3D reconstruction of the heart. And with various softwares, you're able to effectively maneuver in with a cross-sectional slice from different directions to then examine these vessels you are extremely familiar with because you have to understand, um, the the deep anatomy of the heart. And so, they're very familiar freeways, if you will. And it's also how you can tell if there's an anatomical anomaly, right? Okay. So, with that said, there's also a broad understanding of where likely places of plaque will accumulate, which is why the very first analysis that was done in our study is done in a lot of these studies, and it's called a semi-quantitative analysis. It's I like to lovingly call it the horseshoes and hand grenades version of it, which is that a reader within a matter of, how long does it take? Like, 10 minutes, maybe, something like that. Takes a very small amount of time. They're going through with one of these softwares, they're going through and going to each of these predetermined checkpoints, places where there is bifurcation, or where there's, uh, other, um, turns of shear stress, for which there is a likely, um, there there would be more likely a place of accumulation of plaque relative to other areas in the coronary arteries. So, they're going through, they're spotting it, and then they give it a score between 0 and 3. So, it would be just like if we went outside in Las Vegas, and we knew where there were common places where there's accidents in the freeways, or in the different roads, and we go check those corners, and we're like, oh, it seems like this time around we're in fairly good repair. So, this is happening with all of the 200 hearts, or the 200 scans, I should say. It's 100 hearts, two scans per heart. So, that's done. When we That's called a semi-quantitative. When we bring in the quantitative analyses, they're bringing this promise that you're very interested in, that all of us are very interested in, which is they say, we've got something better. It's more granular. It's tighter. And it's more automated. That also brings us the sense that we feel more confident it's going to be more objective, right? But, here's the catch. There's a little bit of a black box effect to it. It's using things like AI, and it's saying, trust us. The training on this is against a whole bunch of other studies. And so, we can know the difference between these scans cuz they're not super super perfect resolution. Sometimes they have little bits in it for which you're going, wait, is that Is that an artifact? Is that something with like, um, you know, something with the scan quality? Is this something that's in the blood, or is it in fact like a soft plaque that's over here, right? And it does its best to interpret that. However, as with all forms of measurement, there is a point where it becomes noise. And by noise, I mean it's difficult to interpret. The resolution of the measurement is becoming l- uh, lower, right? Okay. That's going to be very relevant to this next thing, which is at the point that we were recruiting, we didn't know how low a plaque these folks would be. Spoiler alert, they're low. As a population, our cohort is very low average baseline plaque. By the way, this is something, uh, detractors will agree with as well. Low baseline plaque. So, the follow-up scan, although that that in and of itself should have been a monumental finding, right?

Right. So, average of 4.5 years on a ketogenic diet at these levels of LDL of like 250 254, I want to say is the median average, something like that. But, with low baseline plaque.

Yeah. Okay. So, recognizing everything that I just said, there's an important component that for people listening closely should be very aware of. These DICOM scans, they're capturing the heart in a moment in time. Mhm. But, they can't successfully capture it in in the right moment in time, so that it is always in the right shape to compare to a second DICOM scan that's going to be taken a year later.

Yeah. That cannot be understated. The heart is a moving target. And therefore, the plaque in the coronary arteries around it are also moving targets along these vessels that are conforming and changing in shape.

Yep. Exactly.

That's a big deal. Because what uh cardiologists and surgeons at these conferences, what they like to show are these AI-generated, they look like the vessel and it's nice and long. Those are computer-generated facsimiles of what the vessel looks like. And when there's a lot of plaque, you can feel confident that it's a pretty good facsimile. So, when there's a stenosis that's coming in, it's a little pinch, right? I can say, yeah, I believe it. Because that's not hard to detect. The levels of plaque are easily detectable. And so, with something like a scan rescan in a study, I can feel confident that that's that's going to be accurate, right? But, for us, for our study, uh because there's low baseline plaque, there's even more focus on those artifacts for the smaller bits. And that's a big deal for something that's talked about a lot and not just low carb, but everywhere, which is this issue when you have a low absolute number, the relative number becomes potentially much noisier and a bigger deal.

Yeah. And that's why when we get the second set of scans and our quantitative our And for the low levels of plaque, clearly comes back and they say, there is no noise such that there was any regressors the second set of scans. I can say that seems so implausible because even if you believe

In the lipid hypothesis, and you believe all of our people should have only had progression, it's so low in the baseline that there should be at least noise outshining the absolute levels of progression. But, it's even worse than that. There's a 50% increase relative to the first baseline scan in the clearly analysis. That made no sense to me at all. Because what you're saying is the average 55 years of our of the lifespan of our cohort, the average 55 years, we just happen to catch it in the one year where the average moved up 50%.

Right. Somebody like you knows why that's biologically next to I mean, I have to use the word implausible. The lawyers will get mad.

Yeah. Yeah. But, 100 people having an average 50% increase in their plaque levels was was absolutely it was I just couldn't believe it as I was seeing it, right?

But, on top of that, the fact that there was no regressors in all of the things I just now explained to you, right? All of the aspects that create the difficulty of looking at these scans, to then have the second set of scans be ubiquitous in being uh both only positive calls and and a average of 50%. That's what made it less um less usable in my opinion.

Now, bringing it back to you, Philip, you were one of uh at least 100 people that approached me and said, how do we make sense of what's going on right now? Because after the April 7th paper was released, many people like yourself were aware that this is actually odd, that the semi-quantitative data, which showed low levels of plaque change, even if it was horseshoes and hand grenades, would be so at odds with the clearly analysis. So, we still had the pre-specified analysis to come, the Q Angio. But, thank freaking goodness that we were able to add one more. Because I think it would have been exponentially not as helpful, I'll just say, to have only one more analysis. I wanted one additional, fully independent, operationally blinded analysis, and that's what HeartFlow was.

Yeah. Fully quantitative, yeah. Quantitative, yeah. AI-guided reading. Yeah. But, that was observation that was operationally blinded. Yeah. Which clearly refused to do for us. They would not do an operationally blinded quality control pass. And I'm just super thankful that we did that because sure enough then below the noise floor, below the below 50 mm cubed, we had about a 50/50 between those that were progressors versus regressors. Right?

Yeah. Now, I know this is a very lengthy explanation, but bear with me. I'm bringing this all the way back home to can the me of today, right now, mid mid-February 2026, speak in a more informed fashion back to you who makes use of AI-guided reading for making that determination, are you increasing plaque or decreasing plaque? And I'm going to tell you that given what I know in this moment, I don't know how much I would trust a change of less than 50 mm cubed in plaque as definitely not being noise. And that's because of all the stuff I just explained to you. The problem is that I know these AI companies, they're not going to like me saying that. Right. Because their business model is based a lot off of making the assertion that they can pick up plaque levels. I myself have said it because I'm going off of what they've told me. They can pick up plaque levels of as little as 1 mm cubed or less. That can actually be true. But, how certain of it can we be that it's true?

Yeah. That's the crucial question. When you're working with a population that already has low baseline plaque, my confidence level that you're going to pick up a change is reduced because the resolution is just so low.

Right. So, let me let me just qualify one more thing, which is when I'm talking about that, I'm talking about something called SDC, which is what I'm going to do my talk on, or smallest detectable change. So, the best way to state this is to say, what amount of a change can I feel a 95% or greater level of confidence is in fact a change? Right. And for HeartFlow, I I'm kind of going off the top of my head, I want to say it's something like 60 60 mm cubed. And that's the one data set that I trust most for its level of operational blinding. For anything else, if you're concerned that they're using functional blinding and that they may be overcalling towards say the positive, then that reduces the smallest detectable change artificially. You see the problem?

Yep. And the reason I bring this up, Philip, is because this can potentially apply to the entire field. There may be an artificially high level of confidence in the degree of detectable change of plaque by these systems, and that scares the engineer in me.

Yeah, and you know, uh there's uh I would say even more uh maybe nuance than that, right? When you're actually are looking at these uh images, right? And you know, uh with patients, right? So, there's a couple of things that I've observed. Um again, I I have a bit of a unique practice. Um when my patients get these scans done, right? I don't just get the report, I get the pictures. And we look at the pictures together. Um and you start to notice a few different things. Uh so, two interesting things, and you know, I I can draw upon recent patients that I've seen, right? Um So, one thing, I guess, you know, going back to all the controversy around, you know, the first data set release, right? And everyone's zeroed in on uh the uh percent atheroma volume, right? Uh because this is felt to be one of the you know, best measures, right? When you're using these studies. Um however, there are some challenges, right? Cuz percent atheroma a right? What it means is the total volume of your plaque divided by the total volume of your blood vessels. And there are two variables there, right? And but we don't realize that one of those variables, we think it's fixed, but it's not, right? The total volume of your blood vessels, like you said, blood vessels are conformable. They're expanding and contraction with the heartbeats. They're, you know, bending, right? As the heart is bending and and where you catch it in that cycle or, you know, maybe physiologic changes that have occurred, right? Are going to affect your blood vessel volume, which is now going to affect your percent atheroma volume. So, I have had patients, right? That demonstrably they have a lower plaque volume, but they have a higher PAV because their blood vessels shrunk essentially, right? You know, these are changes, but and especially when you're again dealing with those low levels of plaque to start with, right? That change in the blood vessel volume might magnify things.

Um even more so what I've noticed is uh you know, so we get these reports and it has, you know, how much cubic millimeter of plaque is there and percent atheroma volumes. And then they will report, right? And they segment the blood vessel into, you know, what we call proximal, mid, and distal, right? So, you basically take the whole length of the blood vessel, divide it in thirds, and they report the greatest stenosis within each of those segments. Um and this is something very interesting I saw in a recent patient, right? So, patient a year ago had a scan AI analyzed and it said in the proximal left anterior descending, the maximal stenosis was 81%. And then he comes back to me in the next year and we get the scan again and, you know, same analysis and now it says the proximal LAD the greatest stenosis is 82%. Okay? So, you're looking at the report and you're saying, well, maybe that's within the margin of error.

Um you know, >> Can I ask symptomatic? Uh not symptomatic. Okay. Right? And so, that's why we hadn't done an intervention or anything. Um Sorry for the for the uninitiated, the reason I was asking that question is is for the reason I'm sure you gave that opinion, which is that people can actually have an occlusion that may be even as much as 80% and yet they don't feel any effects.

>> Right. Right. Um and correct me if I'm wrong, the there's not data as it stands currently is that there's actually not a lot to support an intervention when the patient is asymptomatic even in cases of of an of an occlusion of that level. Correct. It used to be assumed >> Yeah. that if about 50% >> that you you absolutely had to place a stent, that kind of thing, but but there's not that the data has since been no, there actually isn't enough of a reason to take steps, but to be aware of it. No question.

>> Yeah. Yeah. But okay, sorry, continue.

>> So, yeah, so, you know, you would look at that report and you would say, maybe he's getting a little worse, probably about the same, you know, uh hasn't gotten better. Right? Uh and then we drill into the images and what we see is, right? So, this 81 or 82% blockage on last year's scan was probably, you know, uh kind of hourglass shaped and maybe that point where it was actually about 80% narrowed was maybe, um let's call it about 4 mm in length, right? Um and then I look at this year's pictures and that 82% narrowing was literally a pinpoint. Hm. And that hourglass had all kind of, you know, opened up again. Right? So, looking at the pictures the only thing I can conclude is this is an improvement, but the numbers don't reflect that. Uh and this is an even bigger challenge, right? That's going to come into play, uh you know, as you're trying to interpret all of this. Uh but um you know, I still go back to, right? When I looked at the uh initial data set from the from the keto CTA publication, right? Not the Miami Heart publication, but from the keto CTA publication, right? I still looked at it and said, these are people that have a lot less plaque than we expect them to. Right. And honestly, even for most of the progressors it was noise. It was within the margin of error or it was, you know, a pretty minimal progression, right? If you're again, if we're going back to the lipid hypothesis, right? That that LDL levels of this level should drive uh pretty noticeable improvement. We're not seeing that.

Yeah, I >> that that was my takeaway as a clinician and um and again, I think it goes back to, right? How much more important the imaging is, uh but you got to be careful in how you're interpreting the imaging.

>> Exactly. Like I'm I'm more I'm more bullish on imaging than ever. It may not seem that way from everything I just said. But no, I stand by what I said at Boca when I was there and you were there. Nothing beats the physical detection of disease. That's very prognostic. It's very predictive as to what your likelihood of future events are, right? And wow, we have the ability right now on a very low dose of radiation to track that predict, you know, that predictiveness as it happens in real time, right? Um but for sure, if a good surrogate did exist for that progression of plaque and that surrogate, you know, is also part of the causal pathway being apoB lipoproteins we've got the data set to help track that. Now, again, I want to be a good scientist. Maybe it's true that 4.5 years is not long enough. However, I want to sit down with somebody who's pro lipid hypothesis and talk out the math because the math, if you're going by I already mentioned Brown and Goldstein many times over. Um they were looking at children with homozygous FH that had LDL levels uh I want to say around seven 780, something like that, right? So, in 3 years, symptomatic Mhm. Um cardiovascular disease with like a stable angina, right? 3 years. So, 3 * 780, you can do the math. 4.5 times uh let's see, our person with the highest LDL was 595. Something like that. Far exceeds that. But on top of that again, our cohort is an average age of 55. So, you add the whole cumulative five decades before the final five years. There should absolutely be a sizable proportion of our cohort with symptomatic cardiovascular disease. And I I I'll go a step further and say that should we get the five-year scans? Would I expect that nobody has had any kind of heart disease or events or anything like that? No, I in fact, I would state the office state the opposite that statistically speaking, statistically, what are the odds that there wouldn't be? If you grab any 100 healthy people >> Yeah. 50 Well, especially if you grab 55-year-olds, right? >> Right. 55-year-olds. >> heart attacks in five years. >> Yeah, and you go and you go to age 60. Yeah. Right? Even if they had low LDL, even if they were healthy at baseline again, just by the sheer odds, some number of them are going to have advancing plaque and what may be symptomatic cardiovascular disease within a span of time. A handful out of 100 would not be that surprising. Yeah. Um again, given it a decade, right? So, there's there's just a lot there. But the bottom line is, would we absolutely expect in a decade's time for there to be a clear association between the LDL and apoB, a clear association? I don't I don't know how you can put forth the simplistic version of the lipid hypothesis without that.

I I think that's really the key, right? Because again, you know, as a clinician um I'm not trying to say right? That uh a low-carb diet right? Is um guaranteeing you you're not going to have heart disease. Right.

>> think a very another very important part of this discussion. Right? What we're what this study is designed to show us is essentially whether or not this lipid hypothesis applies equally to people with this physiology, right? This low-carb metabolic health, you know, sort of physiology. Um and again, you know, as I look at the people in my practice and, you know, the people in the community, right? You know, no one Well, I mean, I I can't say that categorically, right? But I don't think anyone responsible has tried to say that uh going on a low-carb diet is 100% protective against heart disease. Right. Yeah. And there are clearly people within the community, right? There are some influencers now that uh have had heart events Uh and you know again the me as a clinician right you know the default argument there is well of course it's because of their LDL right or of course it's because they're eating so much saturated fat or red meat and then you know what I think is going to be most powerful right from the data that you're gathering is I can say well no it's not. It's exactly so let's figure out what it is. That's why you get it prospectively but do you but let me reinforce your point you're you're 100% right and that if you go low carb not only are you not heart attack proof but I'll comfortably predict that we're going to all populations are going to have heart attacks populations as individuals you know that changes it up but find me any population of 55 year olds that are not going to have heart disease right if randomly if randomly generated. And this is why you do prospective studies. These anecdotes where you're looking even unconsciously for the patterns that fit your worldview that's always going to be a problem because we're humans that's what we do right so if you if you don't believe in the vegan diet and you think low LDL is going to cause cancer independently and those are sure enough you know every time you see somebody on Twitter mention something you're already like collecting in your mind but then eventually you have like nine that you've accumulated well the vegan diet isn't some offshoot diet it's not something practiced by just five people it's actually a prominent enough diet that that association wouldn't be that surprising especially if you're choosing it all a cart by the same token and I predicted this the entire time I think as lean mass hyper responders I'm our Facebook group is nearly 15,000 people. I absolutely predict there's going to be heart attacks within the group I absolutely predict that there is going to be case series that say a you know a terrible set of examples of lean mass hyper responders who have gotten severe advanced cardiovascular disease right but it case series is by definition retrospective. So as the data set gets larger what are the odds that you do not see a popular subset for which there's going to be cardiovascular disease this is why you do prospective studies you want to describe the group in advance then recruit against the description for the eligibility then study them over time. And that's going to give you much better data than what is going to be an unintentional or even intentional cherry picking after the fact. So yes not only is not only is being on a low carb diet not going to by default make you heart attack proof being a lean mass hyper responder isn't by default going to make you heart attack proof all of us have some susceptibility to heart disease. But with all of that said >> [laughter] >> can we put some interest into the levers and how much does metabolic >> matter well like in the case with our study as you saw with my presentation I mean the gist of my presentation was this how much can I find associations that people kept asking me for Yeah. in the blood work well of course part of our eligibility criteria was a CRP of under two you know systolic and diastolic blood pressure that were below metabolic syndrome levels so generally good ASCVD eligibility after all of that how much do we find that association in their blood work with regard to you know it's turns out to be this or that and the the short answer is none. Because guess what once you get metabolically [laughter] healthy people together those associations that are thought to be causal towards cardiovascular disease do not appear to have that association. Brings me full circle back to the whole adjustments in the modeling and so forth I mean until we study until we put more effort to studying healthy populations we're going to keep chasing our tails in my opinion. We have to work at that we had to that's how you can look at something like LDL. Yeah yeah you know and again I think that LDL has become such a distraction right that we don't look at anything else so we we can't you know find these things I do find it interesting you know you mentioned the case series right and I agree right they're not as valuable but here we are you know you've been talking about this for 10-ish years right you know this this low carb movement we'll call it right the revitalization of low carb you know it's been a thing for a good decade now it's interesting to me that I'm not aware of any case series on patients on low carb diets that have had heart attacks right there are certainly enough detractors out there that if this existed I would think one of them would want to say hey look at this you know I found three of these guys right. There is one there there's one that was that was published in JCL and actually was the first it was the first mention of lean mass hyper responders. But the irony is the it was it was around five people. It was self reported so I I don't know for sure but it included the the main person that was highlighted was a female who developed eruptive xanthomas. However she was hypertriglyceridemic. Right. Super super high levels of triglycerides I want to say like 500 600 or something like that and I So not a lean mass hyper responder.

>> I wrote them and I said and I thought with JCL I thought Well this my first introduction to the world of journaling because this is before I published a single paper. Yeah. And they said in the um the editorial or the case series they said run by an engineer this cholesterolcode.com is run by an engineer and I was like oh they're specifically referencing me they're referencing the site so just like I would expect a newspaper I can write a letter to the editor representing myself and you know my thoughtful response and I did that. I wrote one out had I want to say 13 citations and a whole bunch of other it was I we were pretty proud of the work. Submitted to them and they flat out rejected it. Even even though their case series referenced me and they do have letters to the editor as an available it it was I want to say 450 words or something like that. But that was one of the things I pointed out was I said actually this is not indicative of a lean mass hyper responder this phenotype is you're wanting to describe. And it's very relevant to specifically keep all of these lipid values together. There's a there's a reason to not just look at high LDL in isolation. Right. Because it can be high LDL like this this woman who had very high triglycerides because it likely was poor metabolic health. We the the cool thing about looking at high LDL alongside high HDL and low triglycerides is by definition it is almost certainly going to be somebody who's metabolically healthy. And it's common enough that in the low carb community at the time that I was publishing that in 2017 I was like I don't actually even know if I'm right on this. Like it could be a whole bunch of people come forward who are you know struggling with obesity and they're like oh no I have this profile. Doesn't apply to lean folks. No actually it's it's pretty much almost universal. I I I I think the you know the kind of strict criteria that you you know laid out initially I do find that that applies right I do see um I do see not you know I think there's a hyper responder spectrum. And I think I you know I do fairly often see non lean people who have not quite as dramatic but a significant rise in their LDL and but their HDL isn't quite as high or their triglycerides don't get quite as low more so on the HDL the it's interesting right the HDL really seems to maybe be the predictor of that how responsive they are in terms of their LDL cuz you know I see people who get low pretty low triglycerides right down into the 60s or 70s but their HDL is maybe only in the 40s to 50s as opposed to in the 70s to 80s and they get this hyper response but I don't see their LDLs go up to like six or 700 right they go up to 200 or 250 you know and it's interesting to you know and I know you've talked some about this but you know how much of this is a sort of genetic predisposition or maybe it's not genetics, maybe it's that you know, history of leanness. Uh right, cuz it's interesting thinking about people who are relatively lean compared to what they used to be versus people who are truly lean. Right, right. So, I So, I have two thoughts on that. One, it is kind of amusing to me because for a while, I think a number of detractors to the research were saying, "Oh, it's it's genetic and it's actually quite rare." And I feel like more and more of those folks have kind of dissipated somewhat. I think that there is there is more of an acknowledgement that indeed, if you are very lean and you go very low carb, it's more likely than not that you'll develop this triad. It may not be perfect lean mass hyper responder cut points, but to your to what you were saying just now, um the higher LDL typically with moderate modestly higher HDL and low triglycerides, depending on where they came from. So, if it's somebody like say Dr. Tro, who quite literally was going from morbidly obese all the way down to lean. There's this this period of time I sometimes like to call the lipid honeymoon. I don't know the full I have a theory behind it, but I'll talk about that in a moment, but for a while, their LDL tends to be lower. And in the case of Dr. Tro, it was um I want to say even 80 for a little while. And I said on Twitter, he and I were kind of arguing and talking back and forth and he was insistent that, "No, this isn't somebody doesn't have to have high LDL and I myself am not on any medication and I'm down to 80." And I said, "I predict that you're in this kind of honeymoon phase and that ultimately your ultimately your LDL will start going up and will actually start climbing to levels that you're telling me here on Twitter you're going to be uncomfortable with." Cuz he was much more lipid hypothesis centric before. And somewhat famously it did. It started It started creeping up substantially and he was quite uncomfortable with it. What I think is going on, this is my hypothesis. I think that there is just greater remodeling of adipocytes that for people who are morbidly obese is some unknown span of time depending on what their adipose tissue is like. Right. So, as you may already know, if you give it somebody who's metabolically healthy and has never been metabolically unhealthy, they're going to have a whole bunch of small adipocytes. You know, they can uh they've got hypertrophy, not hypertrophy. They've got hyperplasia to where they can make small little baby um adipocytes pretty easily. Conversely, hyperplasia hypertrophy is where there is an adipocyte that's like it's grown >> too large. It's metabolic itself internally is metabolically unhealthy and is even potentially dying and it can even die. And there can be macrophages that come to attend to it. And in somebody who's been morbidly obese for a while, they often have a lot of dead macrophages scattered throughout their adipose tissue. Um it's it's it's basically an a long triaging of your um immune system trying to deal with all of these sick adipocytes all over the place. So, some amount of your regaining your metabolic health of course is not very overnight. It requires getting that whole adipose landscape back into gear. And that almost certainly has some impact on your lipid um profile. And I think I still maintain this, but I don't know how much I'm going to prove to be right on this. I think that a lot of times um cells that are in need, particularly depending on what their enzymatic capabilities are, are endocytosing apoB containing lipoproteins because they can use them. For example, for their lipid bilayer, for things like structural repair, right? Again, I don't know how much of this will turn out to apply, but the engineer in me is excited by the prospect, right? You mean that we might make apoB containing lipoproteins for some beneficial reason and it's not just trying to kill us? It's a thought. It's It's fascinating because this is quite literally how Brown and Goldstein found it in the first place is they saw, "Hey, in some cases a cell intentionally takes up these lipoproteins." And that got them into the LDL receptor and how much of other things. Again, I I hate to keep invoking it, but engineer Dave is like, "Huh, why would we do that? Why would we transcribe these receptors whose purpose is to have a binding domain to attach to the ligand of these lipoproteins by design? I want to understand that better. I want to understand why we do that. Why do inflamed endothelial cells inflamed endothelial cells upregulate receptors to then bind and transcytose LDL particles into the subintimal space? Like the nucleus is drawing up these plans in the mRNA, sending them out, getting the ribosomes to do they're expending ATP Mhm. to make all this very elaborate system happen to to to make these vesicles that then transport Philip, come on. There's There's a a playbook in in place. How much of this is by design versus by accident? Because up because as I was coming into this field, it was by accident by accident by accident and only in 2020 did the same EAS group that gave us the 2017 um consensus on LDL causes atherosclerosis make the mechanics the mechanism paper, where there's that acknowledgement and then you had a whole bunch of people acknowledge that the transcytosis could be a relevant piece of the puzzle for atherosclerosis. But again, that's an active system, not a passive one. And that's kind of relevant to this larger picture.

Yeah, I mean and again, getting back to sort of the uh uh you know, what do I wish to see as a clinician, it's that you know, study like yours and the data and all of that at least gets us to the point of admitting that we haven't fully explained heart disease. And LDL, apoB, whatever you want to say, right, isn't the full explanation of heart disease and what can we do uh to have an even greater impact ultimately uh on it and that's got a the only way we're going to do that is if we take these blinders off that have literally been on the heart disease community for the past 40 years that we figured it out, it's LDL, apoB and we just need to reduce it harder, reduce it earlier, reduce it more um and that's going to solve the problem when clearly it isn't working out that way.

Yeah, it's just uh whatever. It's It's It's a process and we'll get there. All right. I think this is a good place to wrap. Philip, how can people find you? Uh I fix hearts everywhere. Uh all the social medias, go to ifixhearts.com and uh that's where you can find me. Well, thank you for coming on. I've I've been so excited for this one and and I'm glad we finally got a chance to put you on the podcast. Loved being here. Thanks, Dave.