S3E33 Dave Feldman

SUMMARY KEYWORDS

dave, ldl, atherosclerosis, study, high ldl, people, question, lipid, heart disease, low carb, cholesterol, talking, folks, protein, assumed, engineer, metabolically, citizen science, diet, high

SPEAKERS

Announcer, Jack Heald, Dave Feldman, Dr. Philip Ovadia

Announcer  00:10

He was a morbidly obese surgeon destined for an operating table and an early death. Now he's a rebel MD who is Fabulously Fit and fighting to make America healthy again. This is Stay Off My Operating Table with Dr. Philip Ovadia.

Jack Heald  00:35

We did we hear you just fine.

Dr. Philip Ovadia  00:37

Perfect.

Jack Heald  00:38

This is fantastic. This is the first real hardcore nerdy engineer we've had on the show. Well, welcome everybody here. We are joined today by the apparently OCD, Dave Feldman. I've been cruising his website. And I know I say this every show. But God, this looks really, really cool. I cannot wait for this conversation. So, Phil, wind us up. And I haven't introduced the show. Hey, it's the Stay Off My Operating Table podcast, everybody. Y'all know that bill introduced our guests to us.

Dr. Philip Ovadia  01:22

Sure thing. I think a lot of my audience is going to be very familiar with Dave already. And I guess I'll say that Dave's OCD may be what saves us all. But they, first and foremost as a citizen scientist, and really excited to talk with him about that journey that he's been on. And we'll get into some of the details of the ideas that he has brought forth, and, importantly, how he's testing those ideas. So, with that, Dave, why don't you tell our audience a little bit about yourself?

Dave Feldman  02:04

Sure. Well, first of all, of course, thanks for having me. It's interesting. My backstory reads like fiction, it really does. Because I really had no interest in medicine, or nutrition, or any of that, just say, eight years ago. And, yeah, as you mentioned, I'm an engineer. I actually cut my teeth on developing fairly complex platforms of various types. While I liked apps, more recently, we've done a lot of things with high security, gambling platforms. I live here in Las Vegas, of course, so it's not too uncommon to get into things. Oh, yeah.

Jack Heald  02:48

I was there yesterday.

Dave Feldman  02:49

Oh, you were? No kidding. Well, next time you should come and visit. So yeah. I went on a ketogenic diet in 2015. And as many know the story goes, by was just having fantastic results, I really loved it. It was just, it was a great experience. And like many, I was excited to finally see my bloodwork. And then sure enough, I had a big shock. Because while everything looked great, the one or I should say two markers of interest total and LDL cholesterol, the so-called bad cholesterol had shot through the roof. And that triggered my newest obsession, which I thought was only going to take over for a few days. And then it turned into weeks, and then months and now years to try to understand why. And as a software engineer, I thought then, and I'll say today, it's really like a network, like the same kinds of networks that I've worked on my whole life except for more advanced and complex.

Jack Heald  03:56

So, as I was reading your website, cholesterolcode.com, I was thinking, oh, crap, we're going to have one of those high-level scientific conversations. And I'm going to be asking all kinds of questions, begging you to turn this into normal English, or people like me, and you anticipated that. So, Phil, would you maybe pick up where Dave talked about this bad news of his cholesterol skyrocketing after the ketogenic and talk to us about how doctors respond to that, and then we'll take it from there.

Dr. Philip Ovadia  04:47

Yeah, I think that's a good place to start. So, obviously people recognize that oftentimes the singular focus, or certainly the primary focus of those in the heart disease space is around cholesterol levels, and specifically LDL, so called bad cholesterol. And total cholesterol, as Dave mentioned, had been the traditional, have been the markers that have risen to the top in terms of predicting heart disease risk. And the concept that goes along with that is that if you manage your LDL cholesterol levels, if you keep them low, you're going to avoid heart disease. As we've discussed many times on this show, I have made the observation repeatedly throughout my career that that doesn't always happen. And then as I started getting into the low carb space, this other conundrum, we'll call it, arose, that there are many people like Dave is talking about that see their LDL cholesterol levels go up when they start low carb and ketogenic diets. And it's not clear that those people are increasing or worsening their risk for heart disease, and a lot of the other blood markers we look at seem to contradict that. So that's kind of, I think, the question that Dave stumbled on to, and honestly Dave's work was seminal in opening my eyes to this question, because in medical school, it was a totally answered question. LDL, bad, high LDL, bad and there was no questioning that. It was dogma, it was fact. And as you get into it, and we'll talk about this, certainly, we realize it's not quite as it’s built. So, to go back a little bit, Dave, what prompted you to start a ketogenic diet in the first place?

Dave Feldman  07:08

Uh, yeah, well, it was, frankly, to avoid type two diabetes. In 2015. keto wasn't quite that big yet. But it's sort of, I guess, you could say precursor is LCHF, low-carb, high-fat, which is still a term used today. But at that time, I had gotten my bloodwork. And for the second annual test in a row, I'd had an A1C of 6.1, which is right in the middle range for prediabetes. The doctor's office said, well, we'll keep monitoring it. And knowing it was rampant on my dad's side of the family, I was like, well, no, I'm not going to keep monitoring, I want to find out how to interventionally to stop it from happening. And that's what I heard about LCHF, from of all places, diabetes forums. Now, I myself, again, coming from technology, it's not so much that we don't think institutions don't carry a lot of expertise, they often do. And that's why I would recommend people work with their doctors and so forth. But that said, it is also the case that a lot of times we can be distracted by what we're looking for, just kind of the story of LDL cholesterol. But in the case of diabetes, same thing, I think that a lot of the institutions were a bit distracted by what they were looking for, where there was a lot of data that was emerging, that was shown in these forums. And that's why I think I had a lot of trust in them. Now, the irony is, at that time, when I'm asking the same forums, I'm like, Okay, I'm gonna go on a diet, high in saturated fat, and so forth. But will my cholesterol go through the roof? And most people had said at that time, and I think it would be, it would have been accurate to say this at that time, that that was a rarity, that even for those people who did go on a diet high in saturated fat, the vast majority would not see this huge skyrocketing effect in their LDL. And that's the other interesting part of my story, which is that after I'd gone low carb, high fat at that time, my dad and my sister got inspired to do so but they were not as metabolically healthy as I am. They'll concede this, by the way, I'm not saying anything too bad. But they did not see that extraordinary rise in LDL cholesterol that I did. And it's part of what fueled my obsession is that I saw this change, but those two did not. So, that's really kind of what spring loaded is I really just didn't want to get that diabetes and for what it's worth, I've never had a 6.1 and A1C sense of course, as I did, in fact, bring it down.

Jack Heald  09:51

So, like I assumed doctors were, I'm realizing isn't true in the medical profession, but real scientists have a question that they ask. They have a thesis. And they construct experiments, and they observe. And they adjust their thesis and their experiments just to follow the findings. So, if we can, let's back up, what was your thesis? And then take us through that.

Dave Feldman  10:27

Yeah, well, the, the variables, as I just mentioned, the fact that my first set of variables were my own first-degree relatives, that to me, seemed very strongly pushing back against the notion that it was genetic. Because that's where I would have assumed it would be given all the literature I was reading at that time.

Jack Heald  10:52

But what was genetic? This rise or lack of rise in the cholesterol?

Dave Feldman  10:57

Correct. That effectively you can't see, like my LDL cholesterol through my life had been roughly 120 to 130, my LDL cholesterol. And so, when I immediately went to the literature to say, hey, how did that suddenly change from those levels up to say, 230, again, was very alarming to me at the time. In the literature, it would say that, no, if it's above 190, then you have what's known as familial hypercholesterolemia, FH. And that is genetic, that actually is the diagnostic criteria that effectively you can't get to those levels unless it's genetic. And bear in mind, I did not have that much background in reading papers at that time, and so forth. But I thought that doesn't make sense for two reasons. One, because I have these first-degree relatives, the other is because this should have been lifelong. Why would I have had this LDL of 120 to 130? And then suddenly had it at these levels unless there's more to the story? And to your point, yes, from I would say science is like the tentpole, if you will, right, and medicines over here, even if I hadn't gotten into medicine, believe me, in engineering, we're going by scientific principles all the time, we have to be able to develop what we do.

Dr. Philip Ovadia  12:17

Alright, I was just gonna say the interesting contrast between how engineers look at these issues. And I think the medical system looks at these issues, is the medical system is largely accepting of exceptions to rules and we say something like high LDL cholesterol leads to heart disease. And we ignore that there are people who have high LDL cholesterol who don't develop heart disease, and we ignore that there are people with low LDL cholesterol who develop heart disease. And we're willing to take the exceptions, and those exceptions are oftentimes blamed on things like genetics. And you'll just say, well it must be his genetics that are different. And the approach that the engineers and Dave has talked about was that if there's an exception to the rule, there's a prop, the rule is broken. And then you need to figure out what the real rule is around this. So that that has always been an interesting part of this story, to me, is just thinking about these things in a different way.

Jack Heald  13:39

So, you're debugging a problem? A doctor is performing a diagnosis and maybe coming up with a prescription, but you're an engineer, and to you, you've got a bug, or at least what appears to be a bug. You design systems and the system is cranking something out that ain't supposed to be there.

Dave Feldman  14:03

Right? Well, and if you're the system, you have a lot of extra motivation. That's what happened to me. You're going, wait a sec, is the very first question I'm wanting to understand it is, is this a broken system that something cracked and changed? Because the first thing I'm seeing when I'm looking into the literature at that time is that there really are kind of two categories of folks who have high LDL. There's that first group I just mentioned, those who have genetically high levels of LDL, but you look a little bit deeper, and you find that they have some form of dysfunctional lipid metabolism at a cellular level. So, they either had like a mutation with their receptors such that they can't easily metabolize, they can't pull in LDL particles, they have something with the ligand itself so that they can't bind because the protein that wraps it like a bObi doesn't bind properly. So, these are reasons that there's a higher amount that's left in circulation. But that's not the whole story. The other part of the story is the cells are not succeeding at binding and gathering them. And I know that there's a lot of focus on the cells that are in the liver for clearance. But again, not the end of the story. It's also in play for those immune cells like macrophages. Macrophages are right there at the scene of atherosclerosis. And so again, I as the engineer, I'm like, well, if we're looking under the hood, we should look at every aspect of this piece. Okay, so that's one category. The other category is some form of dysfunction in lipid metabolism. That's an acquired disease...

Jack Heald  15:50

Okay. Real quick. Well, you've already used about 17 terms that if I hadn't already looked at your website, I'd be saying you got to define that sooner. 

Dave Feldman

Fair enough.

Jack Heald

Real quickly, I just want to tell our listeners, Dave's website has everything he's talking about, in two different versions. He's got it for folks like me, who don't understand all science, but he explains it very clearly. And then he's got folks like Phil, who all this stuff makes sense. So, the one thing I do want you to back up on, is this chemistry of the macrophage at the site, and what's going on there? And then we'll take it on.

Dave Feldman  16:32

Sure, I tell you what, let me back up even a step further. I've got a good layperson pitch. When we're being fueled by fat, that is going to take a more complex process than being fueled by glucose. So right now, you can go to your cabinet, grab some sugar, and throw it in water, and you're gonna find it just, it evenly distributes into the water. But if you go and grab some oil, if you grab some butter, right, you throw it into water. It's not, it's going to clump together. And it's going to and that's actually a difficult challenge that evolution had to solve for, because we have fat soluble vitamins like A, D, E, and K, that's in our food that our cells need. And our blood is water based. So how did our bodies figure out how to maneuver this stuff into our bloodstream, including not just those vitamins, but fat itself? How can we be fueled by fat if we need to move it around? So, our body makes proteins that help make it soluble in the same way. And that's the genius of the human body that it goes, Well, I'm not going to make just one protein for each kind of fat, I'm going to make one protein that's like a tanker, that all of the different lipids, these water-phobic things can go into like a submarine, and then throw it into the bloodstream, and then it can move around and then have a system that the cells can use to get things out of those submarines. Is that good lay press, so far?

Jack Heald

It’s really good. 

Dave Feldman

Okay, good. Now, you hear the term metabolism all the time. And here's, here's my version of metabolism for layperson. Metabolism is this counterbalance between anabolism, which is the building up of stuff, and catabolism, which is the breaking down of stuff. And metabolism is how good you are at building up and breaking down stuff in a good balance. That's really what metabolism is. And nowhere is that more important than fuel. We care a lot about how good you are at putting fuel away, that you're consuming, and getting it back out. And at the end of the day, no matter how complex all this stuff gets, when people are talking about a good metabolism, we're talking about one that's very efficient at doing both of those. When we're born, we're really good at that. Right? And that's why you'll hear me jump into those two other metrics that I know Philip loves a lot, which is your HDL cholesterol, and your triglycerides. Triglycerides are that cargo in those submarines that are the proteins that we'll talk about, and HDL and here's the part that I myself didn't really understand to the degree that I do now, until the last few years. The reason higher HDL cholesterol tends to associate with better metabolism, whether you're on a low carb diet or not, is that it's actually kind of a proxy for the successful level by which you're putting fuel away. That's what's pretty fascinating about it. So, when you see HDL being high and triglycerides being low, whatever your LDL level is, you probably are good at that process of metabolism. How am I doing so far?

Jack Heald  19:47

Um, this is great. I think I'm getting it. My brain feels like it understands.

Dave Feldman  19:54

So, the last part of the puzzle is exactly what I was talking about before. If you've got a broken system, to where you have an incapability of putting fuel away, whatever diet you're on, it's not surprising to see your triglycerides go up because basically what that means is there's a traffic jam that's going on with those proteins, they're failing to get that put away into your tissues, especially your adipocytes, your fat cells. And another part of that failure of putting it away is that there's less of those components from that first version of protein over to the second, which is the HDL. HDL has a particular protein that wraps it called ABA-1, you don't need to memorize that, but you do need to know that we make a bunch of them, and we leave them in circulation to pick up a lot of the stuff that's part of that, that turnover, that process of putting it away. But the big reveal is what's that famous protein that's bringing all of these lipids in, it's a very, very famous one called ApoB. And the major class of lipo protein, this macro complex shat means all of that in there is an ApoB containing lipoproteins. And if it comes from the gut, it's a chylomicron. If it comes from storage, predominantly, it's a VLDL. But the VLDLs famously remodeled to LDL. And that's what excited me was, as I was learning more about this, the more I was like, well, actually, I think what's happening to me and not to my sister and my dad, is because I'm leaner. And because I run a lot more, I'm trafficking more of these ApoB proteins because I need to move more of them into circulation, I need to use more of them. And I also need to put them away and take them out at a faster rate, all else being equal. That's what I think. And that was the beginning of what I now call the lipid energy model. And it's why I think it explains why paradoxically, the people with the highest LDL and ApoB levels, and a low carb high fat diet, or this phenotype I'm very focused on that not only have very high LDL, but they also have high HDL, and low triglycerides. And it's extremely ubiquitous, it's across all these different ethnicities, all these different ages, all genders, everything. That's what excites me as an engineer.

Jack Heald  22:26

Phil, I could ask a lot of stupid guy questions, but this is probably where you need to jump in.

Dr. Philip Ovadia  22:32

Well, so what I think would be interesting to discuss is you develop this theory which, like you said, is now kind of known as the lipid energy model. And you identify this group of people with this unusual cluster of results, we'll say, the high HDL, the low triglycerides, and the high LDL, and that is now been coined the lean mass hyper responder, and what was the response that you've got when you started bringing forth these ideas? And I guess I'd like to hear about who seemed interested, who didn't seem interested? And what kind of response did you get from the various communities on these thoughts?

Dave Feldman  23:34

Well, yes, this was another place where it got a bit interesting, because I think I've, at that time, sort of assumed that a lot of folks who are certainly a lot more educated in lipidology than I am, would take this and run with it, like it was just a matter of getting it to the right person, and then they would be snatching it out of my hands and being like, thank you very much, that's very nice, as an engineer, we can take it from here. Certainly, we're very interested in how it is that some folks could have this high LDL in a dose-dependent manner based on how lean they are, and how low carb they are, things along those lines, which, in my opinion, wasn't, again, it was prominent enough that I would have thought a lot of people would be very interested who study cholesterol in particular, as not just a profession, but also as a field of science to see how this would relate to the pathologies of such as atherosclerosis. Because here's the hard truth. The hard truth is that the vast majority of the data that we have that links high LDL to atherosclerosis are on those two groups I was just talking about, those folks that have some form of dysfunction in lipid metabolism. We actually don't prospectively study folks who have high LDL but are otherwise metabolically healthy. It's just assumed that you can extrapolate that data from those other folks that have some form of dysfunction, and that it'll apply to those people who are healthy. So, yes, there was...

Jack Heald  25:16

This is kind of like, you take a group of folks who have suffered polio, and you note that their 100-meter sprint times are all excessive, are all over 30 seconds. And, and you reverse back and say, people who run over 32nd 100-meter sprints are all crippled. You're confusing the cause and the effect, am I getting it right? Maybe not the right analogy...

Dave Feldman  25:49

I actually have an analogy that I like a lot. Which is, it's often said, and I agree, that ApoB containing lipoproteins are causal for atherosclerosis. If you go to the scene of atherosclerosis, you will find ApoB. And therefore, if you take steps to lower ApoB, interventional steps that bring it down as low as possible, you'll have a net reduction of atherosclerosis. So that statement that it's necessary, sorry, I hope I'm saying this correctly, necessary but not sufficient. It's a component of the process, I fully agree with. It just doesn't tell me enough, because that's kind of like saying, car tires are causal for car accidents. That's objectively true. You need car tires to enter into car accidents, but do car tires drive car accidents? Because if we took steps to ban all car tires in a city, we would find that there's less car accidents. The question is in doing so, is there a trade off? Is there for example, because I may be taken to the hospital in a vehicle has car tires, right? So, the next best question to ask, which is what I did back in 2015, is to look to see if it was say like smoking. Whereas the lower and lower and lower you get with smoking, the greater and greater longevity you would see. It was the first thing I went for, I was like, okay, well, how does LDL associated with longevity, because presumably, the lower you go, the greater the lifespan. And to my surprise, I did not see that. In fact, I saw some studies that actually showed the opposite. Now there's some recent studies that would say, no, there is some level in some Mendelian randomization studies, that would say no, there is some level for which if you have a higher LDL, a first degree relative could show some increase in mortality. But that's not where I started, where I started was, look, if high LDL and particularly high ApoB is causally inducing atherosclerosis, then it would seem that people who are lucky enough to be born with as little LDL and ApoB as possible would have a clear signal of longevity, they'd be out living a song, like that would just be pretty obvious. And to date I’ve not actually seen that effect, there's one study that came out, you'll have to link it in the show notes that was on PCSK9 loss of function that went to millions of person years, and they did see a reduction in cardiovascular disease, but not a reduction in all-cause mortality. And that, to me, says quite a lot that there may indeed be some kind of a tradeoff that might be in play for reducing atherosclerosis, but possibly this has an impact in non-atherosclerosis. Again, it's theoretical, but certainly one I would be interested in exploring.

Dr. Philip Ovadia  28:55

Yeah, so just to highlight that the view in the medical community is that LDL cholesterol or ApoB, depending on who you're talking to, is clausal of heart disease, and it by itself, having elevated levels of this can cause heart disease, is the primary driver of heart disease. And that idea is so ingrained in the medical community that you can't even question it. So, I know that Dave has gotten a lot of pushbacks from some of the leading lipidologists for even asking this question, for even considering it to be a possibility that maybe there are situations where you're having high ApoB, high LDL is not causative of heart disease, and in fact may prolong life and the other issue we have is what Dave was alluding to as well, that we have sort of lost the context of LDL. And the general thinking in medicine is that LDL is only related to heart disease and ignoring that it may play other roles in the body. Because we need to drive it down at all cost to drive down heart disease. So that's the environment that Dave has been asking these questions in. And to Dave's credit many people would have just sort of backed off, I guess, at that point and said, Okay the experts, the lipidologists, they certainly must know what they're talking about. But Dave has persisted with his theory, and has taken it to the next level, because he couldn't find that lipidologists to run with the ball. And so, Dave ran with the ball himself and designed and is in the process of doing experiments to test some of these theories. So, that's what I'd love to get into next, Dave, is talking about the way that you have been trying to validate or like any good scientist disprove your theory, because you have said many times, and I think I've heard it from almost every time I've heard you speak, you admit that you might be wrong, but the only way to know is to test it.

Dave Feldman  31:33

That's exactly right. So yes, to kind of complete the other part of the story, I'm sharing this research and discussing this model. A lot of folks are becoming understandably curious, a lot of folks are becoming alarmed. And a lot of them are like me in which they're both, right? They want to understand what's going on. But there is a genuine concern that there might just be this willingness toward having standing levels that are of high LDL, when in fact, they could be causal. And exactly to your point, I have said it many times over. I hundred percent could be wrong. And even if I feel, as I like to say often cautiously optimistic, I'm not going to stand on that. I want to actually gather as much data as possible. So of course, many people have shared a lot of their anecdotal data. And while we don't have them written up as case reports, I am in regular contact with folks that are the highest level of LDL and ApoB, and usually are these lean mass hyper responders for medical reasons. They're on a ketogenic diet, for example, due to severe epilepsy. From their perspective, they're willing to take the chance on how high their LDL has gone, because they're having difficulty with different medicines that are seeking to lower LDL, and they're keeping closer monitoring. And so, they feel it's their choice to do. I always caveat to those folks, look, this is uncharted territory. And course, I'm sure you're hearing it from your little bit lipidologists. But I'll repeat it, it may indeed, be extremely high risk and don't take any level of optimism as the gospel. But it's those folks who definitely motivated me a lot to say, look, let's just get a study together, it seems so obvious, right? Now that we finally do have some folks who seem to have functional lipid metabolism, that they may have a high LDL for this different reason that there isn't a traffic jam. In fact, it may be the exact opposite, that there's enormous traffic flow. If we are to believe that ApoB containing lipoproteins causally induce higher levels of atherosclerosis, then those folks I just spoke of should be showing the signs like right away at a population level. And if they're not, should that induce us to more actively want to study this prospectively, then yes. And so, in 2019, I got up at one of these conferences. I said, you know what, I've formed a public charity called the Citizen Science Foundation. And I want to just raise a lot of money so that we just do our own study, let's go ahead and make it happen. And the low carb community stepped up to their credit, and helped us fund the study that's been a lot of what I've been doing to date is both raising the money to make this happen, then designing the protocol, getting through IRB approval, and fortunately getting partner and Dr. Budoff, who is a luminary in the field of CT angiography to do this study for us and Philip, and I'm sure you'll appreciate this, in the beginning, they were saying you'd be able to do this given just how high their LDL levels are, would like say 30 people, maybe 40. And I was like, I want 100. I want 100 participants because you hear a study that's on 30 people, 40 people, of course, you should be able to go by things like statistical significance, and exposure levels. But you know a hundred is a little bit more of an emotional number for all of us. It kind of breaks into the next range for us. And I'm proud to say that yes, we just now, just literally this last month, scanned all 100 of our first visits. And as I know, your cohost may not be familiar with this, Jack. But the other part of the study is everybody who gets single first scan, with this a CT angiogram, will then get a second successive scan one year later. So, we'll have CT angiography to compare between the two. And that way, we can actually see if indeed there is this rapid progression of atherosclerosis at a population level, which is what would be predicted right now by the existing lipid hypothesis.

Jack Heald  35:53

Okay, let me ask a possibly dangerous question. Assume your hypothesis is correct, that the presence of high LDL is not, does not... Let me take it farther. Assume your study shows that there is no causal correlation between high LDL and heart disease. Who do those findings threaten?

Dave Feldman  36:27

Well, let me roll you back for a sec, because I want to qualify. First of all, the study we're doing right now, I'm actually going to dilute the excitement level of it to some degree, because as a good scientist, we should properly say, hey, I'm only testing a particular context. So, I'm testing the particular context of lean mass hyper responders and borderline lean mass hyper responders with their high LDL when it seems to be metabolically induced. So, I can't make a categorical claim, even if I had 10 studies like this, that is around LDL all together. But I will say that if the lipid hypothesis, as it currently stands, suggests that in all contexts, we should see this inducement of a higher level of LDL and atherosclerosis, it does challenge that, it challenges the overallness, if you will, of how much LDL causes atherosclerosis, right?

Jack Heald  37:25

So, you're that actually guy on the on the internet, aren't you? Actually. Okay, Phil. You're not an engineer. If Dave is right, whose ox gets gored?

Dr. Philip Ovadia  37:43

Well, I think, what Dave and many others have been talking about, and certainly what I have been talking about is, right now the perception around LDL is it's an absolute, LDL high is bad. And I have had plenty of clinical observations that go against that. The literature is awash with observations that go against that. But all Dave is trying to do, and all that I would hope would come out of Dave's work is that we can at least reopen that conversation that maybe not all high LDL is bad. And there are contexts where certainly it may be bad, and there are contexts where it's not bad. And if we can at least open up that conversation, of course, it starts to challenge the prevailing environment today, that all high LDL is bad, and therefore we must lower everyone's LDL. And obviously, that's been pushed by the pharmaceutical industry that has an interest in this. And quite frankly, the lipidology community has kind of staked its specialty on that, that's what they do. So, I think bringing more context to this discussion is all that Dave and others are asking for, and that's why I think this will be such an enlightening study, because it's the Black Swan kind of theory. Once there's one black swan, you can no longer say all swans are white. So that's what we're trying to figure out here. That's what Dave is trying to figure out. So, I'm really excited to see where these leads. And I guess with that, I'll say that this has already led to another step in the process. And that's what I was really excited to bring Dave on today to talk about is kind of the next step in the process of figuring out this unanswered question.

Dave Feldman  40:14

Yeah, thanks for teeing that up, it hasn't been a, what you're referring to, I would call in the technology business, a soft launch, because I haven't actually stated this very openly and actively. But at the low carb conference that we were both at, I got to share with the audience at that time that indeed, the preliminary data for this study, those first 100 visits, were so compelling that we're now in talks for putting together a companion study. So, at first, we assumed that this first study would need to get to its completed stage before we do what's known as a confirmatory study, a study in succession. So, after the first study is done, we do the second study. Frankly, this initial data has just been so astonishing. We're so confident that it's novel, that I'm already talking with some of the donors. Right now, I'm already talking with the Lundquist Institute on the next design. And we think that we're going to be putting together a companion study in the near future, the companion study will have some things that the current study doesn't, such as a control group. We’ll actually have a more relaxed eligibility criteria. But in effect, what we're looking to do is again, see if lightning strikes twice, see if to get to the black swans, right, it's not even just a black swan, because some people will use the example of the 90-year-oldld who smokes three packs a day. Now, on the contrary, you shouldn't be able to identify a group of people, given the existing lipid hypothesis, who you say, hey, I've identified these folks, and they have the highest LDL, and that they're in the top 10 of the top 1%, like our current population for this current group. And yet, they don't have this pronounced increase in atherosclerosis, that would be expected, given the existing literature, the existing lipid hypothesis as it stands today. And if that doesn't, if that shows in one study, it can be very groundbreaking. If it shows in two studies, at least two or more studies, that's the point where you actually have confirmatory data that could really change the landscape.

Jack Heald  42:31

So many questions I want to ask Phil.

Dr. Philip Ovadia  42:36

Yeah, fire away. I mean I'll just say that I'm very excited about this. And that again, what I'm excited about is that this will hopefully spur the, let's call it the mainstream medical community to take an interest in this question. Again, if the study results come out in such a way that it looks like this is a good theory, then the onus is on the medical community to run the run more studies, because that's the definition of science. And Dave's results need to be reproduced to be able to be accepted. And I think the onus is on the scientific community, the traditional lipid community, we'll call it, to disprove if Dave's experiment looks positive, then what was wrong about Dave's experiment or what aspect of it can we then disprove?

Jack Heald  43:55

Well, I will say it, I don't, again, I say this occasionally, I don't have a license that can be taken away. So, I can be a little bit reckless, I guess. But there is a multibillion-dollar drug that has made a lot of people very wealthy for a long time that would be put at risk, its usefulness would be shown to be not what we were told it was. I'm actually being more careful than I normally am. The whole purpose of a statin is to lower LDL.

Dave Feldman  44:42

I'll still man that a little bit, even though I'm trying to be careful whenever the discussion of cholesterol lowering medications come up. I think that there I think that there are sort of two schools of thought. There are some folks who are pro LDL lowering who would say, well, statins may not be worth came through the lowering of LDL. But they do have, maybe they're anti-inflammatory. Maybe they're just more successful through other means. But I do and I think Philip agrees on this one, I do push back on whether you can hold both positions at the same time. Can you state that the reason there is a reduction in, say, cardiovascular events in secondary prevention is due to lowering of LDL? Or are there things since every drug does more than one thing, are there things for which there is some value? Well, I would encourage the medical community to get to that greater level of specificity. But I think the point that you're coming to, and certainly one I'm interested in, is can we just acknowledge that maybe there is efficacy in some of these drugs for like, say, secondary prevention, that shouldn't just by default, be assumed to apply to primary prevention for people who are metabolically healthy? Why not just study folks who are metabolically healthy? I would encourage the drug companies to do a primary prevention low risk study to see how their drugs affect the population. But I'm doubtful that that's actually going to happen, because of course, it would cost a lot more money, it would have to have a longer time span. And I don't know how much I can count on them making that data available to do retrospective studies or anything along those lines. Regardless, I would hope everybody would agree on this one tenant, which is you don't want to put somebody under any medical therapy for which there's clear data that suggests that there's no good reason for it. So, in that regard, yes, I'm, if they're not doing it, but we're at least helping to put that data together, at least it's happening, at least now we'll have some idea as to how much it matters or doesn't, specifically the LDL lowering portion of it.

Dr. Philip Ovadia  46:58

And the reason this is so important as Dave alluded to is there are plenty of people who are benefiting greatly from these diets. And they are being actively discouraged from staying on these diets, because of this issue, because their LDL cholesterol has gone up some. And so that's why I think this is such an important question for us to answer. Because there are unintended consequences of this lowering LDL at all costs approach. And there's these specific dietary approaches that people are taking. And then quite frankly, there is the overall dietary approach that has come out of the diet heart hypothesis, the low-fat diet, that at this point, has clearly done damage on a societal level we really have all the evidence we need of that. We've had 40 years of low-fat diets, and our health, as a society, has clearly worsened during that time. So that is the bigger question or the bigger issue that I think answering this question can help us get to.

Jack Heald  48:23

Well, this is one of those where I really just want to take Dave off into a corner, and make sure I got him alone for about three hours and just pepper him with questions. And I commend you, Dave, your circumspection, your clear, scientific approach, dispassionate, objective approach to the problem. Thank you. It's really cool to talk to somebody like that. And for somebody who's basically a bomb thrower like me, it's also a little maddening. But you've done a great job. I know folks are listening to this and everyone, okay, I want to know more. Point us in the right direction.

Dave Feldman  49:08

Well, of course, you just mentioned the site cholesterolcode.com. The foundation, citizensciencefoundation.org, is where we also, if you want to make a charitable contribution to our study directly, you can do it by going to citizensciencefoundation.org. I'm happy to say by the way, we have a 0% admin overhead, the only money that is taken as for like third party services, such as credit card processing, and so forth. But that's literally why I created the foundation was so that there would be no conflicts of interest discussed because there's not a penny I make or anybody who's involved on the design side, it all goes to the research and the Institute and so forth. And then of course, there's, I’ll mention our service, Own Your Labs, but that's because my entire partner’s share goes also back to Citizen Science Foundation. But Own Your Labs is a private blood testing service that we have where people can basically order their blood work, we have an additional citizen science component to it, which is that you can opt in to take the citizen science discounts, 10% off if you provide your anonymized data for our anonymized data archive, which we intend to be making available for citizen researchers. Because unfortunately, there's not a lot of open data on low carbs. And I'm happy to say that a lot of low carb people go through our service. So, we'll eventually have that data up and available, and then people can make use of that as well. And of course, I'm very active on Twitter, sort of Philip will attest you can, you can usually get a hold of me if you need to have a quick question or something like that. @realDaveFeldman.

Jack Heald  50:48

The real Dave Feldman, not one of the myriad counterfeits I'm assuming

Dave Feldman  50:54

There's a lot of Dave Feldmans on Twitter, that's for sure.

Jack Heald  50:58

All right. Well, as always, we'll make sure all that contact information is available on the show notes. And, Dave, thanks, man. It was every bit as good as I'd hoped, and not nearly as long as I wished. Thank you. Please come back.

Dr. Philip Ovadia  51:16

Yeah, we'll definitely have Dave back more as we get some more results from the study, and we'll just keep pushing this along. So, thanks for all the work you're doing, Dave, and I look forward to hearing what comes of it.

Dave Feldman  51:32

Thanks for having me on. Pretty good

Jack Heald  51:34

Till next time. We'll talk to you all.

Jack Heald  51:43

America is fat and sick and tired. 88% of Americans are metabolically unhealthy and at risk of a sudden heart attack. Are you one of them? Go to ifixhearts.com and take Dr. Ovadia's metabolic health quiz. Learn specific steps you can take to reclaim your health, reduce your risk of heart attack and stay off Dr. Ovadia's operating table. 

Jack Heald  52:12

This has been a production of 38 atoms