David Feldman
Appearances
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Well, there's waist to hip ratio. Of course, I'm listing off the things that are in metabolic syndrome. There's high fasting glucose, high A1C, but that gets back to insulin resistance.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Honestly, I feel like this shouldn't even be debated anymore. I'm stunned, and I kind of get on a soapbox about this, but I'm stunned that there is so much attention still paid to LDL cholesterol, or for that matter, its major carrier, ApoB, relative to
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
to insulin resistance syndrome relative to poor metabolic health when without question, poor metabolic health isn't just bad for overall mortality, but specifically to cardiovascular disease. If we're talking about cardiovascular disease risk, That should be one of the first places the conversation starts.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Because unfortunately, there are a lot of folks, including some challenge cases within my own family, who hear, hey, if you get your LDL cholesterol low enough, you're a low heart disease risk. And the data just does not support that. You have to care about being healthier yourself, particularly when it comes to metabolism.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
The study centers around a phenotype I had named in an article in 2017, lean mass hyper responders. So like myself and many others who I was communicating with at the time, we don't just have the high LDL cholesterol. But on top of that, we have the high HDL cholesterol, the low triglycerides. So, of course, high LDL is considered a risk factor independently.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
So when you get your quote unquote lipids, the lipid panel has four different markers on it. One is total cholesterol. The second, the one most people are paying attention to is called LDL cholesterol. Often the mnemonic is that it's the L for lousy, lousy cholesterol. Then there's HDL cholesterol, which is the so-called good cholesterol.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And high HDL and low triglycerides, they're associated with lower cardiovascular disease risk. But as I'm sure you see on social media all the time, they're, again, considered to be secondary, that they're not ultimately going to protect you from sky-high levels of LDL. In identifying this phenotype, I went knocking on the doors of lipidologists and cardiologists and research saying, hey, let's...
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
study this phenotype. To put it quite plainly, most of the interest is in studying populations that are already at severe risk, including having these metabolic problems. Well, I just got done explaining the lipid energy model with regard to why there might be high LDL from heavy successful trafficking of the cargo of fat.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
I would argue that its counterpart, known as atherogenic dyslipidemia, where you have low HDL high triglycerides, is where there's more of a traffic jam. Unfortunately, all of the research is focused there. It's almost impossible to get scientists to be interested in studying, especially prospective studies on folks who are especially healthy but have high levels of LDL and ApoB.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
But that to me is crazy given the fact that you have the variable of interest that we're all focused on right there, perfect for an experiment. So after two years of trying and failing to do this, I said, what the f**k? I'm just going to start my own charity to fundraise for the study that we want to have.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
So the critical question is, are folks who have sky-high levels of LDL and ApoB but are otherwise metabolically healthy, are they going to show that association? Is it going to bear out? The high LDL will associate with a corresponding increase in plaque. I start Citizen Science Foundation in 2019 and I'm raising money after that point, as well as getting together with a protocol team.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And ultimately we find our principal investigator and Dr. Budoff right here in LA at UCLA at the Lundquist Institute and managed to raise enough money to where we can actually make this study happen. It was, they said that we could do this with 25, 30 people given just how high their LDL cholesterol is. but I wanted a hundred. I knew that was ambitious.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And I basically was telling the community this at the time that was fundraising. I said, you know, I can cut off at any time, but I, I estimate it'll be about $2,000 per lean mass hypersponder participant. So at 50,000, we have enough to go off of, but I, I'd love to get a hundred, but that'd be $200,000 and credit to the low carb community. They stepped up and put that money together.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
The key question is that question. But to get the best data, I didn't want to do multi-center either. I want to fly everybody here. And another thing that's not normally done in studies is we placed all of the participants in a hotel to spend the night so that they would be rested and so that their fasting blood work would be complete.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
So all 100 participants per the study design were flown here and they got what's known as a CT angiogram. It's a high resolution heart scan where they actually, they take them through a CT and they get a CAC test on the first pass to find out how much calcium they have. And then on a second pass, they have contrast dye applied. And that scan is coming at them from all directions.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
to be able to pick up a very high resolution to where you can actually identify plaques of one millimeter cubed or even lower in some cases.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And then there's triglycerides, which is a measure of fat in the blood. Usually a doctor is looking at those first two. They're looking at total cholesterol or they're paying attention to LDL cholesterol. And the ranges for that, total cholesterol per the guidelines, they're supposed to be 200 or less. LDL cholesterol is supposed to be 100 or less.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
It's both. Yeah, we're picking up both soft plaque and calcified plaque, basically all plaque. They get this on their first visit, and then they're to return a year later to get a second scan. So all participants get a total of two scans. That's a total of 200 scans. Now, after we got that first set of scans, we've already published data on it.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
You and I had already chatted about it before, including the Miami Heart match, which looked at another study and compared those first initial scans with the Miami Heart cohort. But this was especially of interest was the longitudinal. That's what they call it, where you're getting it in two separate points in time.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
would we see an association between LDL cholesterol and the progression of plaque at an individual level?
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
That by the way is the average. It's around the average of where our participants is.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
That's an important question because our eligibility was they needed to at least have been on the diet and at these levels for two years for baseline. I was stunned to find out that we had over, it was half a decade. Half a decade was the average that our participants were at these levels.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And naturally, I found that to be very exciting because now we have some fairly strong data, even at baseline, of how much their plaque levels would associate. But then we'd also have the progression. So even though the progression is being measured over one year in the longitudinal, you add that to the baseline. of the 4.5 years before that. So this is a long span of time.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And then frankly, they don't pay much attention to HDL and triglycerides quite the same. Now, my historic LDL cholesterol was between 120 to 130. And my doctor was usually like, ah, it's about the average of what I see for an adult male. But it would be nice if it was a little bit lower. But I go on a ketogenic diet and my LDL, goes from that 120, 130 up to 250. So naturally, I'm quite concerned.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
I also want to drill into something that's kind of important, really also distinguishing the importance of looking at 80 versus 180, because the present lipid hypothesis is not that 180 is about twice as bad as 80. The present understanding is that it's log linear, which is to say with each increase, for example, in LDL cholesterol of 39 milligrams per deciliter,
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
There is a further increase in risk that continues to go up exponentially.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Yeah.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Absolutely. And so, of course, there's a clear expectation of an increase in likely plaque for just how high these LDL levels are. I mean, Brown and Goldstein, their work is 50 years old at this point, but they had a patient that they describe as pivotal to their whole research trajectory because she had an LDL of, I want to say it was around 700.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
and saw a rapid development of plaque to where at age three, she had a stable angina. And at age six, she was having myocardial infarctions. It's sad, but it's understandable why when they're seeing that association, they're going, wow, this really hits the strength principle of Bradford Hill such that it looks like this really is causal since after all,
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
She doesn't have any of these other risk factors, right? She's not a smoker, she's not type A, et cetera. So bringing it back to the average levels of our participants, The average of ApoB being 180. This is a very, and it's a wide range.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
We even had, I think, I think our participant that the highest LDL was close to Bradford Hills or sorry, it was close to Brown and Goldstein's patient because it was, I want to say 590 LDL. This was one of, this was the outlier on the far edge. But she did not have a high reported plaque at all. She actually, I think, had one of the lowest.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
The snapshot after the year, it actually completes the full scope of the study. That's what we raised the money for.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Well, it's right there in the title. So I'll reveal the title. Of course, many may already know it by this point. That plaque begets plaque. but ApoB does not. So let me take both of those. The first and most obvious thing is that if there was existing plaque at baseline, it was very correlative with what the plaque progression to be expected would be.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
That's correct. But ApoB, and for that matter, LDL, did not associate with plaque progression. And we already know from what we already published that it also didn't associate with what showed up in the baselines. We have yet in our data set to have an association between LDL cholesterol and and ApoB with either plaque presentation or plaque progression.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And my doctor says this is like one of the highest cholesterols I've seen. And I almost never see somebody change to this level of cholesterol because usually it's genetic. That's where the tie-in with my dad and my sister are relevant. They go on the same diet about the same time. They don't see this jump in cholesterol. And that's what got this whole obsession going for me.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Correct. And we should unpack that a little bit because what we published before was called semi-quantitative analysis. So it's through human readers. The data we're publishing now is actually using AI-guided reading, which gets really granular. And it's through a company called Clearly. They do some just amazing analyses.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
But they'll find plaque in every scan. Yeah. And there's nobody who's going to send their scans through that they won't find plaque.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
I don't know that I could actually speak to that specifically. As the funder, I'm technically blinded from data to the extent to where there might be some – as you're kind of – you're sort of suggesting there's a dotted line of sorts to where there might be plaque below a certain threshold for which there would not be an association. That's possible. It could be in a substrata situation.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
That could be found. But my understanding from Adrian, who isn't blinded but also wasn't part of the funding initiative – he's the biostatistician who's in charge of this and, of course, the first author of the paper – was that broadly correlative – It's just there. It's just that the lower the amount of plaque that you had at baseline, the less progression you would likely see moving forward.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
But again, then you've got whatever is going to come in the next year and the year after that and so on and so forth. Right. That's why I'm very interested in us doing a third set of scans. I'm currently in the process of raising money for us to do an extension. So we I don't know if we'll be able to retain all 100 participants. It may be like we lose a third. I don't know for sure yet.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
But that'll be an interesting question to get answered as well.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
First of all, I think for me personally, and I can only speak for me, I've wanted there to just be some dataset for which- Yeah, because there was none. There wasn't. There was no dataset that looked prospectively at people with sky-high levels of LDL cholesterol, but who didn't have some other independent variable of development of atherosclerosis.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Okay, so for example, taking it back to Brown and Goldstein, I mentioned the little girl that they were looking at. The genetic disease that results in the high LDL is itself, this is homozygous familial hypercholesterolemia. I know it's a big word, but super important illness because it has an impairment in lipid metabolism. for why there's the higher LDL.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
But that same impairment also independently associates with greater risk. So people have HOFH.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Yeah, literally one in a million, by the way. If they have this disease, even with aggressive lipid management, The same level of LDL for somebody who has no genetic predisposition for it, and they already had this before we did our data, has a difference in risk. Now, there's this other factor. The other factor, and this is kind of why I brought up the lipid traffic jam, as it were.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
If you're metabolically unhealthy and you do have lower HDL and higher triglycerides, you will likely have moderately higher LDL as a result of having metabolic syndrome. I want to repeat that for extra emphasis. What's resulting in the lower HDL and the higher triglycerides also tends to result in the moderately higher levels of LDL.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And then when you check out ApoB, usually their ApoB is off the charts and they tend to be pattern B, like I mentioned before. Why am I bringing this up? Because temporally, when you're becoming metabolically unhealthy and you get this lipid profile, that's a cluster. It's all these different things together.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
But then you become healthy and you manage to reverse that, all of the markers head in the other direction, including LDL. So LDL going down and associating with lower cardiovascular disease risk for people who have metabolic syndrome, it's confounded by the fact that the LDL is going down, I believe, as part of, for example, repair with the adipocytes.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
You have less adipocyte hypertrophy, for example, right? And I think that's very relevant when you get back to the lipid trafficking. Okay, so in that case, how much can we be sure about the independent atherogenicity, the plaque-causing value of LDL and ApoB? That's why we needed studies on people who are trafficking it but not having the traffic jam to get a better sense of that.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And that's why we needed this study, because now we could get it away from that cluster. That's why I that's why, yes, for me, that's the big takeaway is finally we have population data and we need more. We need more population data that's looking at metabolically healthy people with this variable of interest in and of itself.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
My position still remains more in the realm of uncertainty than certainty. I realize we're in a space where people love to just throw out their, you know, the broad categorical claim. You're fine if you're on X diet, you can ignore Y marker, right? And this includes LDL. Do I feel better? With regard to my own high LDL and being metabolically healthy, given these data, I do.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Does that convert to not only do I feel certain that I'm fine, but I'm willing to go around to everybody else I know who's a lean mass hypersponder and say, you're fine. No, it's not there. It's not there yet. In fact, I feel that we've just got to continue to build on the existing data that we have.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Moreover, within the population, so we're talking population data, within the population, there still may be a number of participants in our study who are on the further end of the outlier side. that have plaque that actually want to take steps to do something about it.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
The thing is, I have the kind of freedom where I can just say that I'm mostly living in the unknown and then just be very cautious whenever somebody asks me on a should I question, which I'm sort of famously on Twitter saying, I don't answer the should I's or the will I's or anything along those lines. I'm just trying to get the data and turn it around to you. Now, second to that,
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Can I identify a number of my friends, this includes Nick Norwitz and Adrian Sotomoto, this includes Matthew Budoff and people we work with like Brett Scher, that there's this emerging category for which they're looking at data like this. And as clinicians, they need to still have something they can say to their patients. Is there a consensus? There is.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
There's an emerging consensus that if you go on a ketogenic diet, and your LDL cholesterol goes sky high, then an obvious next step to strongly consider is getting some imaging. If, for example, you get a CAC and your CAC is zero, that's actually some really strong data right there that at least in the immediate term, there doesn't seem to be much risk.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Almost everything, including data that precedes this study of ours, reinforces that. Again, this isn't medical advice. This is me just pointing to what they're saying. Conversely, any of those two qualifications aren't met, they would say, I'd feel more comfortable if you did something about your LDL or your ApoB.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
If you're not metabolically healthy and or if you have some existing disease that puts you to medium or high risk, maybe you should consider taking steps to do something about that. Again, this is not my opinion, but I'm comfortable repeating what they're saying just to at least have this discussion take place.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Without question, the conventional view right now across really every single organization around heart disease is that high cholesterol is high risk. End of discussion. The higher your cholesterol, the more at risk you are. And you'll often hear phrases like the lower, the longer, the better. Because
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Yeah, you said CT scan, but I think you, and specifically you meant CAC.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Yeah, so in a – which is a CT, but it just – if we're being specific, the agonist score is what you're talking about.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
It's true that if you get a CAC, it's not picking up soft plaque, and it's possible that the soft plaque could be more of a problem than you realize. Right. That said, I will tell you, I've become so much more bullish on CAC in recent years because of certain studies like the study out of Denmark that was phenomenal. They had 23,000 patients.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
between two set points of years, and these were symptomatic patients. That's part of why they got a CT angiogram, for which you could see how correlative the CAC was with the CCTA, right? That actually calcified plaque is a pretty strong indicator of your real risk level, right? Now, that said, gold standard, 100% should be a CT angiogram. But
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
I want to say, and I may be wrong in this, but I'm pretty sure I'm right. A good example that they had in that paper that I read was there was only one of those people who had a CAC of zero. There was only one in 250 that had at least one occlusion of 50% or more of soft plaque.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
So in other words, the level of disease of soft plaque being extremely high, surprisingly, in spite of a CAC being zero, was super low. So without question, if it's a family member of mine and I'm concerned, Legitimately, I'm probably going to ask for them to do a CT angiogram. But the catch is that they do, they're definitely a lot more expensive than CAC.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And there is the potential risk of contrast dye, you know, beyond the higher radiation. Contrast dye is very low as far as having one of the complications. I think it's like one in 10,000 is that there might be something with the kidneys that lasts a little bit longer.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
But for those folks who are like, well, I just don't want to get a scan, at least a CAC makes it a little bit easier because it's cheaper, it's available more places, and it's at least a fairly straightforward pre-screen.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Generally speaking, no matter what, just like a smoker, if you smoke three packs a day, sure, there's the once in a while example of somebody who managed to escape getting heart disease or lung cancer. But as a population, everybody who's smoking three packs a day is at risk, even if they're otherwise healthy in every other respect.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Generally, at a population level, it's very rare for somebody in, say, their 20s or 30s to have a positive CAC. That said, it's not so rare that somebody may not want to think about it again if they have some reason to care. This is the thing I never feel like I can say enough. Nothing beats the predictive power of the existing presence of disease. You just, you can't come anywhere close to that.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
So if you have reason to think, especially if you've got a very severe family history of heart disease, that you may have some existing disease, you may even want to consider it, say, in your 30s. Now, us men, we tend to get the heart disease a bit earlier than women. So we tend to have at a population level, the majority of men having a positive CAC, I believe starts like late 40s to early 50s.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
For me and my family, again, not medical advice, I'd like to see a CAC at least by 40. And just to see if it's a zero. A zero is a good number because it usually means given present data, even for those people who have concerns, that you probably won't need to take another one for another five years. And let me give actually a radiation dosage comparison.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
It's about one and a half times that of a mammogram. So it's really low. I want to say it's 0.6 millisieverts, and it may have even come down further on newer machines. Now, into the 50s, both men and women, that's where the population average tends to head towards a positive CAC.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
I can't speak as much to what the ranges are, but if you do have a positive CAC, usually if it's 1 to 99 before crossing over 100, You want to look at what your own population average is for the age to get a sense of where you stand. Are you in like the bottom 25% or et cetera?
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And so these organizations you're talking about, this landscape, the guidelines are quite clear that if you've got high LDL, you've got to take steps to change it. That's where these ranges come from, like having the total cholesterol under 200 and LDL under 100. And they'll say that it's better for it to be even lower.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Now, there are a lot of people on the cardiology side that would say, look, any positive score, you need to now start treating like it's secondary prevention. But you may want to read up on Karam Nasir, who is really into CAC. He's published a lot on this, and he has some interesting breakdowns that clinicians make use of as well.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Where it gets interesting is you're talking about what levels of concern you should have at what stages. For folks who are, let's say, in their 70s or even 80s, my parents, for example, are in their 70s. I have the expectation they're going to have positive CAC scores. I wouldn't be surprised in late 70s if it's above 100%.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And then you kind of have to start working with what you're going to be doing about it and what they're willing to do. I don't know about your parents, but my parents have, they're already working through a lot on the healthcare side of things.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And so there's a degree with which I'm trying to at least get enough detection to know just how close the issue is to best figure out what care decisions they'll accept, right, that we can do.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
But can we use this exact opportunity to bring it back to metabolic health? Yeah. I've told them this many times over. I've said that the biggest thing is I want you walking. I want you to try to lift stuff here and there. Staying strong to me matters the most, as well as getting some cardio, staying up and about, keeping your metabolic health available is going to help your health span go longer.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And it's a huge cardiovascular disease risk to let it go. Specifically, cardiovascular disease risk. And there's plenty of good data on that, especially as you get older. Your return on investment just gets better and better for the time you put in, as long as you can keep them in that mindset.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
A hotly debated topic. There are two broad hypotheses that were coming up through all of last century. One is called the response to retention. The response to retention is that our arteries have cells called endothelial cells that line the vessel walls.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And in time, a concentration gradient, if you will, of all of these particles, like LDL particles, eventually passively push their way in to our arterial wall. And then they start to develop plaques. Macrophages, which are immune cells, they're kind of like Pac-Man. They come over. They're trying to swallow them up because they're supposed to clear out debris, but they get stuck. They get stuck.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
They eventually can die. Other macrophages can come there and they produce something called a foam cell, right? Now, that one hypothesis, the response to retention, suggests that it could happen everywhere just through the process of how high those LDL levels are.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
There's this other one called the response to injury, which suggests that actually it's the injury to the endothelium that results in the plaques that we're seeing. Now, this one's been mainly confirmed. In fact, we prove it in animal models all the time. We do things like denude their carotid arteries, and that can actually create plaques that we can then study past that point.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
But the response to retention is, to be fair, is not mutually exclusive. It could be that both are true. However, I'll concede very early on, I had a lot of trouble with the response to retention as stated. because I would have expected more of a Gaussian distribution across all of the arteries.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And that guides a lot of the food choices because I'm sure you hear saturated fat can potentially be bad. Why? Because it can be associated with increased LDL cholesterol and therefore you should eat less saturated fat and hopefully get lower LDL cholesterol. That's the intent.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And where it accumulates the most is in places of greater shear stress, bifurcations, places for which you'd expect more mechanical deposition through potentially damage.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And definitely lots of coronary arteries where there's a lot of pressure. It's important to remember, even though we can never be reminded enough, the heart isn't just a muscle that's pumping our blood. It's conforming in shape on a constant basis. So those arteries are moving a lot. So try to imagine if you're an immune cell trying to do repair and the whole landscape is shifting around.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
To me, it just always made sense that that's got to be a more challenging space to operate things like afrocytosis, which is the process of like tissue repair. And so I am not surprised that where there would be lots of vulnerability for things like the response to injury, that that would make sense.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
For me, I do think things like blood pressure, I think things like hyperinsulinemia being relevant toward this development of atherosclerosis makes sense above and beyond the ApoB-containing lipoproteins like LDL. But I will be, and I'll emphasize this again, I do think that in both cases, ApoB-containing lipoproteins like LDL are part of the causal pathway of atherosclerosis.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
First of all, I had no interest in nutrition, medicine, even really science that much as much as I did engineering. And so I've been a software engineer my whole life for the first, let's say, four decades of my life. And then I'd gone on a ketogenic diet. And going on a ketogenic diet, I just felt great. It was so wonderful.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
So the development of plaque itself, 100% agree that if you look into those foam cells, you're going to find ApoB-containing lipoproteins and you're going to find macrophages that are dying there and so forth. But to say that they are the central drivers, that they are driving atherosclerosis, I always felt that there had to be more to the story.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And really, this paper, these data are maybe some of the strongest I'm aware of because of the sheer magnitude of our participants' levels. It would be one thing if our participants were, say, an LDL of 160 and, you know, ApoB of 100. But no, no, APOB of 180 and an LDL, I think our average is 255, something in the neighborhood.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
That's in the top 1%, actually the top 10% of the top 1% of the regular population. We should 100% have seen a signal if this was driven by the response to retention hypothesis predominantly.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Or at a minimum that there would be a correlation. Correlation. So at a population level, there was a plaque increase. But that was fully expected because that's going to be any 100 people. You could randomly grab the healthiest 100 people anywhere. And at a population level, especially if they're middle-aged, you're going to see a plaque progression.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
The bigger question was inside that group of 100, would we see even a little bit of an association between how high their LDL and ApoB was? Because again, we had not only an average that was very high, but we had a lot of heterogeneity between just how high it could get. Some folks were right there at the 190, 200. That was just right at the edge of the eligibility.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
But you had some people that were 400 LDL. I mean, wouldn't we universally expect to see that they would at least be at an average, those 400s above those folks that are at the 190s? I mean, per Brown and Goldstein, yeah, that would be the expectation.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Well, first and foremost, injury is just part of the game. Your vasculature, it's already well known, is on a constant state of injury and repair. Like that's just what happens. It'd be the same thing as if we pulled everybody on this block to find out who has like never had a scratch applied to them, who is completely scar free, even at the smallest levels.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
It's just it's not going to be the case. Right. So. There's, of course, the natural process known as apoptosis. How can an endothelial cell that's literally the barrier between the blood wall and your subintimal space, how can it kill itself properly so that it can be replaced with another endothelial cell? Well, that's a process. And that does involve a site of inflammation.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
It might be very tiny, but that does involve immune cells. It's just baked into the overall playbook, right? So some injury is to be expected just in the same way that you would expect the roads outside this studio would undergo repair from time to time. So- There's a process known as hemostasis, which is if there is a tear that's opened, primary hemostasis is like a platelet plug.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
It can just kind of easily cover that injury. It's very simple. But secondary hemostasis is if the tear is like larger and that actually involves a clotting cascade and it's way more complex and so forth.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
So I posit that somewhere between something in that neighborhood that we can already study, it's relatively innocuous, the repair happens relatively easily, to this other end of the spectrum, which is fully calcified atheroma. Between there, I think, is a range. And I believe that there's a lot that happens.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
There's a lot of plaques that form that are in the same way, just like we'd have an injury on the outside, repaired just fine. It's just that it's not easy to study and measure. But have we seen people who, given certain protocols, ultimately appear to reduce their plaque burden on net? Sure. The catch is that usually that's something they're very proactive about taking care of.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And there are a lot of things that are involved. But we still have to get more science on that. I just think that the injury itself, to get to your larger question, what can cause these injuries? I think that's actually a large list. A lot of things that can be introduced in the blood that as much as we're trying to control the filtration of coming in, we know there's things like gut permeability.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
At the time that I was coming into low carb, and this is 2015, 2016, a lot of what was being discussed was the particles themselves getting a more advanced test than lipid panel I just mentioned, such as an NMR, nuclear magnetic resonance test. And that led to the discussion of the big fluffy versus small dense particles. This comes back to the work of a scientist called Ronald Krauss.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And therefore, pathogens can come in. There's also ways in which it can be it can be infarcted by not just things mechanical, but things, for example, like bacteria, so forth. But I think it's worth reemphasizing some amount of this is just to be expected. I think the story of atherosclerosis is less about those initial injuries.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
I think it's more about the inhibition of repair, the failure of our immune response from taking care of those potholes that eventually become bridge collapses, right? That I think is a more interesting question. So if you are hyperinsulinemic, if you are eating around the clock, Are you out-competing your immune response? I think you are.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
I think things like going on a binge are actually potentially deadly. But you may not know it today or this weekend when your buddy came into town and wanted you to do shots all week and then eat pizza all night and so forth. But you might have created a lot of turbulence that ultimately opened up a wound you can't feel.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
in your LAD that seven months later or seven years later becomes your next heart attack.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
It's a, but yeah, I use this analogy a lot. I don't know if I did this on the last podcast with us, but think of breaking your leg and then think of not knowing that you broke your leg, but you keep walking around on the broken leg. So you make the injury more and more complex and more and more difficult to repair when you finally end up going to the hospital, right? I do believe that...
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
the nature of how the injury occurs may be unpredictable. It may be that the weekend of binging didn't create a problem, but it could be the marathon you ran the weekend after did. And then you not taking enough time to recover on it actually is what did in that, that tear that made it worse and worse and worse. You, you said, I feel great. I'm going to actually do 10 more morning runs.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And if you've got a lot of these LDL particles, but they're big, they're larger in their size, generally they're considered more buoyant and fluffy, and they're considered less atherogenic. People who have this pattern for which there's higher and higher levels of the big fluffy have what's known as pattern A. But pattern B is where you have more and more of the other kind, which is small dense.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
In fact, I'm going to prove this to my wife. She says, I don't, You know, I'm always too broken down to be able to do repeat runs, and I'm going to prove her wrong, so I'm going to do 10-mile runs for the next five days on a bet, right? This is why I think, by the way, a lot of extreme athletes have ridiculous CACs. They have huge CAC scores, and they go, I don't understand why.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
I'm as healthy as an ox. I'm doing everything right. And then my first question whenever I have a friend that tells me this is I go, do you recover though? Do you really take time to rest off those injuries? Because I believe that there are internal injuries that, again, you can't feel. You cannot feel. There's not nerve endings to every endothelial cell.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Which would be great. Like if you could wear some device that's actually monitoring the composition of your coronary arteries so they could actually pick up when something like this happened, I'll bet it would change the whole landscape. But as you know, from her study, just getting a CT angiogram is a bit of a production.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
This is a little outside of my wheelhouse, but as you know, the heart's very electrical. It's based on a sinking cascade, right? And so I have always been kind of curious how much of that comes back to electrolyte usage. I've certainly ran into not getting enough electrolytes when I was doing running initially that I needed to have way more salt than I was giving myself credit for.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
When I was a runner. Yeah.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
It is, but here's what I'm going to bring you back to my original unknownest philosophy. That's how I like to call myself is I live more in a world of uncertainty than other people are comfortable with. I'd be willing to bet we know Maybe 5% of those things such that we can prescriptively try to avoid them. And it turns out there's another 95% of things we have yet to discover are injurious.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
I do feel more confident in what it is we can do that inhibits the immune response and not do that.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Okay.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And therefore, a lot of people who are low-carb who even had high LDL cholesterol were saying, well, but I have pattern A, so I don't think I'm that much at risk. But even then, there was still a lot of debate. There, yes, were a number of people were saying, I just don't even care that much as long as I'm pattern A. I don't care how high my cholesterol goes.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
So there's a, there's, and I wish I had the paper in front of me, but there's a threshold of insulin that at above a certain level is going to put your immune response in more of a pro-inflammatory state then. And this actually kind of comes back to how it's an anabolic hormone, right?
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
So there's a lot of great research that's on this from my colleague, Siobhan Huggins, who was really looking into this way back, I want to say like seven, eight years ago.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And it was fascinating because she was putting a lot of these papers in front of me that indeed showed this like delicate balance the immune system kind of counts on in what I like to call the closing hours, which is when you're sleeping, right? When you're no longer eating and before you're entering your circadian rhythm, that's when a lot of the best immune work happens.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
So when you're suddenly feeling like you need to rest, you need to be laid up, I think you need to follow that instinct, right? When you're sacked out, you're tired, I'll bet you that it's a huge cardiovascular disease risk when you're enforcing greater consciousness, especially if you're eating during that time.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
The one piece of health advice that almost everybody knows, I'll say that I feel like I could stand on, is not to eat, say, three to four hours before you go to sleep. It's the one thing I try to hold the tightest to because I want those closing hours for my immune response. And that way I can also ensure the insulin levels are lower.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
That way I can ensure hopefully there's no engagement by my GI tract from food that's still working its way through digestion. You know, GLP-1 agonists get a lot of discussion with regard to medication. But the first time I was learning about GLP-1 is that how food in the hindgut can have an impact on stimulation with insulin, for example, right? Yeah.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
okay, I want all of that off the table so that I can maximize my recovery potential to leave that available for my immune response. Now, the thing that I also speculate is sometimes that may not be needed, could be even most of the time, that may not be needed to be completely on target. But
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
It's needed enough, I believe, as evidenced by those people who seem to be out competing their immune response from those two extremes. People are not only metabolically unhealthy, but those folks that are waking up in the middle of the night hungry and eating, they're usually near the void, frankly. If you're somebody who's in a place where you feel like you have to eat around the clock
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
The data does not look good for you. But on the other end of the spectrum are these massive overexercisers. They're getting such an endorphin rush. And the runner's high, which I've never experienced, by the way. I still feel like it's a hazing ritual. Those people who I've met some, I've met ultramarathoners who just cannot go one day.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
There were definitely a lot of people who were saying, well, you know, I could be more okay with my LDL being, say, 180 or 190 i have a problem with it getting up there to say 300 400 500 And that was a new phenomenon. Even within the low-carb community, that was actually pretty new.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
They can't go one day without running many multiples of miles. And often, often they have severe heart disease. So you've got to prioritize recovery.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
I eat two meals a day, one at 10 a.m., one at 5 p.m., unless travel kind of throws that off. But that's generally the pattern I shoot for. And it's not because I'm just obsessively into intermittent fasting or anything along those lines. I care the most about that window before going to sleep.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
So it's rather than trying to fit it within a certain mealtime range or something, I allow for I can eat as early as I want to. I don't mind that aspect of it. I just, to your point, I like eating at 5 because if I'm up to 9 p.m., 10 p.m., Even if I start to think about it, I find that I have better control, self-control and recognition that I'm just wanting to do it because I'm bored.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Because enough time has passed where I'm starting to think about food, not because I'm genuinely hungry for it, but because it's boredom eating. And I feel like that's just a Western society phenomenon, right? Only because we often have things like lunch breaks where we start getting aligned to when does this fit into my schedule? When does this make sense from a time allotment standpoint?
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
But to your point, I personally think our ancestors were almost always exclusively eating during the day. Oftentimes competing with each other for like, you know, the hunt comes back and the meat's finally cooked and everybody's trying to get their take and probably eating it as quickly as they could, right?
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Even where food starts to get towards where it's being preserved, there's a lot of ritual involved. even to this day in a lot of societies, around the food and not to treat it like we kind of do here in the U.S. It's kind of like something you're going to eat off your lap in your car while you're on a Zoom with some other coast trying to get something done, and it's just an afterthought.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
It's one thing, by the way, I liked when traveling to Europe especially is they're in Europe. Their meals tend to stretch out over a while. They tend to be smaller portions. And I think that that's a lot healthier. They also, by the way, their restaurants close much earlier than ours.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
I'm going to do my best to give a very brief overview of what I would call the lipid energy model, which we've now established and published with the enormous help of your prior guest, Nick Norwitz and Adrian Sotomoda. The three of us have actually codified a lot of this into the literature, but this is kind of how it works.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Yeah, pretty much.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Well, certainly, and again, I should qualify, I don't know how much of this applies to the heart specifically because it depends on whether or not there's a backlog there to take care of, right? So existing heart disease, here's some things that I'll just state up front I think are very plausible, easy things to infer. There is a rate limitation.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
There has to be for virtually any bodily process, given that you can only make so many immune cells. You can only have so many of them active at a given time. And therefore, another thing that I'm mindful of is rate limitation just by sheer quantity. So if you're already battling a huge inflammatory response, There's a lot of data that backs this up as well.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
You're at a higher risk of heart disease. I think a good piece of that is that there's a rate limitation. The very same macrophages I'm talking about, they come from monocytes that differentiate into macrophages. Macrophages, by the way, are one of my favorite cells of the body. They're amazing. They're incredible. But... Can you have unlimited monocytes in production and in constant?
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
There's some limitation. I don't know where that stands. But I think if you've got systemic inflammation from multiple other processes, it's a backlog problem. There's going to be only so much that it can attend to at a given time, right? But then there's also, as I mentioned earlier, the complexity of the injuries themselves. So...
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
If I've got complex injuries elsewhere in the body, let's say I have severe burns. It's another great example of something that can often associate with greater risk for a heart attack. I think it's quite possible that there's a degree of occupation by my present immune response.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
that is now in competition with what might be happening elsewhere in the body, particularly with regard to repair in the coronary arteries. Again, I always want to be careful to emphasize these are hypotheses, but I think that we have a lot of data in hand that definitely substantiates how much the immune response relates back to exactly what we can do about atherosclerosis.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And hopefully remove those barriers as much as possible. And one of those, I think, is watching those inflammatory markers in your blood work to at least confirm or disconfirm if there is something of a systemic inflammation elsewhere.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
We're constantly talking about metabolic health, but what is metabolic health? What actually establishes it? Well, metabolism is that balance, right, between anabolism and catabolism. You're breaking down and building up. But what we're usually talking about is fuel.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
I like glyca a lot. Glyca is really great. Ferritin could be considered a, I mean, it can also relate back to iron, but I like it also as an inflammatory marker. A lot of the interleukins are great because they can also give you greater specificity. Another good one is TNF-alpha.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And yeah, myself, I really like C-reactive protein. It's a very high sensitivity, nonspecific inflammatory marker. So it's not great in regard to diagnosing something of specificity. But let's say your CRP comes in at under one, pretty decent chance you don't have something inflammatory going on.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
A lot of the advice I give people when they're dealing with, for example, something that they understand to be autoimmune is I say, you may want to consider getting a C-reactive protein test at least to determine if this is related back to inflammation.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Because if there is an immune response in play, that at least tells you one large category of things to then investigate in over here with regard to that immune response. And that means that the body's aware of it. And that means that the body is implementing a plan to attack it, deal with it. And that gives you a direction to go. Or it doesn't.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
You're experiencing these symptoms, but there doesn't seem to be inflammation related to it, at least not as at a systemic level. That's also useful.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
So when you're consuming particularly something like carbohydrates, you're storing your fuel as stored glucose, which is in the form of glycogen. That's fine, but that's a small container within your body, whereas fat, we have a fairly large container with regard to our adipose tissue.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
I know I've watched in real time as these. Gosh, I want to I don't want to poison the well, as it were, because I do want to both the gentleman that you mentioned. I've had many great discussions with in private and to some degree in public.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
For example, with Simon Hill, I've been on his podcast and I've had discussions with Lane Norton, both in private and also at Low Carb Denver not too long ago. I would love to have the kind of conversation you and I are having now with them after the publication. What I think the response will be, because this seems to be where the new position has moved, is, well, this is a tiny group of people.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
So it used to be, well, there's too much of a setup that these folks are metabolically healthy, and therefore that's in its own way putting them on the scale. I welcome that change in that that's not what the position was when first talking about lean mass hypersponders because there was a sense of, well, it doesn't matter if they're metabolically healthy.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
They're still going to be at high risk for having a high LDL, ApoB. That's what most of the critics of our research were originally stating.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
As more and more of these data had been released, and I think because a lot of even the cardiologists have more of a patient pool that includes lean mass hypersponders, I think there's been a broader recognition that maybe they're not at a population level at high risk, such that that's kind of being quietly conceded, right? I don't want to put words in their mouth, but that's how it seems.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
To where now the new statement is, This lean mass hypersmart research is not that interesting because this only relates to this tiny fraction of people. Now, if that's the case, if that's where sort of the new position is, I don't mind that in regard to a lot of people that are featured in our movie, Cholesterol Code movie, as you know, is going to be coming out soon.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
is not folks who are using the ketogenic diet for weight loss. They're actually using it for efficacious reasons. You mentioned bipolar earlier, right? Nick Norwitz himself has been using it for his ulcerative colitis, a schizoaffective disorder with Lauren Kennedy, for example, right? There's Metabolic Mind, I'm sure you're familiar with.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
So if you've got good metabolic health, if you're good at pulling the fuel out and putting it back away again, but you're powered more by fat, What's relevant, that fat in the blood needs a carrier. And the biggest bulk carrier are these complexes called lipoproteins. So that LDL I mentioned earlier, that's short for low-density lipoprotein.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
They're doing all sorts of great research and a lot of new videos and so forth. They There is an important distinction we need to make for people who are finding a big solution with the ketogenic diet, but the one thing they're afraid of is the one thing I was afraid of 10 years ago when I saw it. They just want to know, is the risk level there at a population level?
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And if folks like Simon Hill and Lane Norton are willing to acknowledge, okay, but they're part of a tiny fraction, that's a big jump right there. Because quite literally up until now,
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
It's just been a broader sense of, no, the existing data that we have on the disease populations informs us for the healthy populations so that we can make this claim that, no, it doesn't matter what your circumstances are. You have high LDL, you're at high risk, end of discussion.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Type 1 diabetic, right?
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Right. I'm sorry. It's an answer they deserve. And I'm appreciative of everybody who's helped to contribute to make this thing happen because- While I obviously have helped a spearhead get this thing going, this is as grassroots as it gets.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
I'm so thankful for Nick Norwitz and Adrian Sotomoda for every step of the journey in helping to make this happen, for Matt Budoff, but particularly for all these people who've contributed, who literally reached into their pocket, gave us the money to make this science happen that should have already been happening.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
There should be not only the interest in looking at whether or not this level of LDL will associate in these folks that are metabolically healthy, but specifically for people like you're talking about who are using ketogenic diet for therapy. Not just as another way to... Most people who are type 2 diabetic, and I will sound not like a low-carber right now, I would say they have lots of options.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
They have lots of options to try to take care of it. But virtually all the options are going to be, to quote Ben Bickman, virtually all of these options are going to be some low-insulin version. So if you can calorie restrict and you can find that's just something you like more than, say, low-carb, that's fine. But for some people...
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
So these lipoproteins, if you're trafficking them more in the body, particularly if you have to move more of those fatty acids around, it gets a bit complex. But we would argue that cholesterol is ride-sharing in that process, in these containers. That's the reason why you're seeing higher LDL cholesterol.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Ketogenic diet is the one and only thing that they've been able to find that helps them with their medical condition.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And at the time I was training with running and so forth, I was setting personal records. I lost a bunch of weight. And I thought I just kind of found the fountain of youth and couldn't stop telling my friends, especially my family, my dad and my sister adopted at the same time.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Because in short, if I have to release more fat and then replete it back again, and I have to power my muscles more with fat and so forth, that metabolism, that pulling the fuel in and out, I have to have... get carried on these ApoB-containing lipoproteins like VLDL, which remodel to LDL when they drop off their fat-based cargo in the form of triglycerides.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Well, of course, I've got to reassert. My answer to your question shouldn't be taken as here's my advice to you to give as advice, right? Yeah. I will say here are the two broader school of thoughts. One is the statins are the way. And it doesn't actually matter why there's the change. Statins are just the best heart disease medicine.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
So if you have existing plaque, that's just the direction you should consider going. One of the more interesting things that I've seen change over time with regard to that school of thought is that it doesn't necessarily need to be maximal dose statin, typically 80 milligrams or 40 for some of the stronger ones. I think even...
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
I don't want to put words in his mouth, but I think even Peter Atiyah was suggesting you get, what is it, 85% of the benefit from like, say, five milligrams, five milligram statin or something like that. Yeah. And then there's another school of thought that is, well, whatever alters your LDL is because it's the major contributor.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
You could go ahead and use something like enzetamide, which limits cholesterol absorption in the gut. And for what it's worth, in the Lean Mass Hypersponder Facebook group that we have, many people would discuss strategies that they want to take on if they're not comfortable with their high LDL. And zetamide is probably the single most popular intervention to bring down their LDL.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Listen, there's just so many people who are in this exact position where they're listening to multiple sides, which by the way, I do encourage, listen to multiple sides who say, look, I feel mostly this way, but you know what? I'm going to kind of, in my mind, I'm going to be hedging my bets by going this other way, right? And to that extent, it's all your own personal health journey, right?
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
To be a good scientist for as exciting as these data are that landed, the five-year data could more substantiate the lipid hypothesis. It's possible, right? To be truly open-minded, we've got to be able to say there are still other possibilities that we couldn't know until we have longer data to be able to substantiate it anyway.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Could well be that there's a subset that we're not yet aware of for which higher LDL will show that association and everybody outside the subset doesn't exist in that fashion. You'd think I was pouring cold water on my own data by just saying these things, but no, this is just part of that living in the uncertainty and accepting it.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
You work from the data that you have, not just as a clinician, but as a patient, right? So it's not a bad thing to be able to say, here's where my comfort levels are. And here's what the data show. I just hope you can do both. I hope that you can have, whoever you are, I hope you can get a good barometer for where your comfort levels are.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And I hope you can care about getting enough data to make an informed decision for yourself with your doctor.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
I think there are a number. I'm not sure how much of this is embodied in Atiyah per se. I think he really does believe that ApoB is... Like if we give ApoB low enough, we just... As I think he puts it in his book, that it'd just be an orphan disease. That cardiovascular disease would effectively go away if we could find a way to just make it... So for example...
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
They're trying to develop means by which it's like CRISPR to give people PCSK9 loss of function. But here's where I may sound like I'm an ultra LDL skeptic or sorry, an ultra LDL lowering skeptic. As I said on Simon Hill's podcast, and as I'll say here, I don't know that there's not a tradeoff.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
In most things for which there's an intervention, probably arguably all things, there's a trade-off and you want to be sure that you're on the profit side as opposed to the loss side. I do know, and I should at least defend, that ApoB lipoproteins do serve purposes in the body, including LDL. For example, they bind to pathogens, they carry alpha-tocopherol, which is an antioxidant,
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
I think they're also made use of, for example, for structural demand, which kind of gets into parts that we don't yet have published in the Lipid Energy Model. I don't think that it's consequence-less taking steps to lower LDL. It doesn't mean that I think it's necessarily on net a bad thing, but I think it's possible. And...
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
In that regard, I'm not going to start with that assumption that there's only benefit to be had. Now, if you only had that opinion, then I could understand the advice because then you're casting a wide net, right? And even if it was benign to change your LDL levels for a lean mass hypersponder who's metabolically healthy, no worries because the other 80, 90% of the rest of the populace that is
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Almost. This is where it gets tricky because a lot of times when I'm talking about this, folks say, well, wait a sec, the major cargo, the fat that's being carried by lipoproteins is triglycerides. I mentioned that as part of the panel. But a lot of people go on a low-carb diet, and this includes myself, would see their triglyceride levels in the blood test go down. So how can that be?
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
unhealthy would potentially see benefit from their perspective and taking steps to lower their LDL. Possibly, that's all possible. But I don't like that approach in general. If that's kind of the thought process, because what you're describing is, hey, we need to find guidelines that are going to apply to the majority out there, but lack nuance by design, right?
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Because if you're trying to push forward nuance, you're asking questions, you're getting specifics so that you can say, here's the data that best applies to you that we have. As opposed to giving broad statements and saying, we're going to try to one size fits all. Because when you do something like that, you end up with these awkward positions where you treat all BMI as overweight if it's high.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And most Americans who have high BMI are over fat as opposed to over muscled. But there are some that are over muscled. Should they take the data that applies to BMI to apply to them universally?
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
I'm not even sure on this one that, which may sound odd. I don't, we don't. I don't feel confident enough that we know the cycle of plaque progression and ultimately plaque cessation or even regression to be able to know for sure. We don't have good trajectory data.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
So in the same way that you might get a wound on your arm and for a moment while the clot is forming, it could look like it's terrible if you extrapolate from that, that it's just going to continue to build and build and build. I don't know. I don't know if you went on a perfect diet on day zero. but you're one of these friends you described. You had a terrible lifestyle before up to age 40.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And then right then, we knew the perfect protocol for you to go on, diet-wise, all the right supplements, everything. That on day zero, plaque halts. I doubt that. We already do have some decent data that non-calcified plaque is gonna be more likely to get calcified, and that's usually a good thing because it's getting more stabilized. Statin producers would say this as well, right?
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
But how much of even soft plaque progression might turn out to have a net benefit under healthy conditions? I don't know that we can say. I don't know that we have a good answer for that. I already take enough heat for just suggesting that that's a possibility. But so many things in the human body work that way.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
If I'm saying you're moving more of these around and you're powered more by fat, well, in truth, the model is positing that there's just more successful delivery. So taking a snapshot of your blood is kind of like taking a snapshot of an active shipping lane that's out there in the ocean, but most of the boats don't have cargo in them. Why?
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Again, getting back to embracing the uncertainty, I don't think that that's a bad thing. This is another reason why I want to get the third scans, not just so that we can treat this as one giant score that's either going up or it's going down, but I'd like to see three points along the way, just because I think we could get better at answering this exact question I'm putting forward to you.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
I think a better way of putting it is take it out of the shoulds. If you have plaque at baseline, can you expect there's probably more plaque in a year? I think we have pretty good data to suggest that yes, even if you're metabolically healthy and you have plaque at a population level, there seems to be some data suggesting you'll probably get more.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
How much more seems to correlate with how much you started with.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
I think that's going to be a very individual choice. I can tell you what I know. Me personally, if my, let's say I took a CAC today and I found out my CAC was Bear in mind, I'm 51. So my CAC would be, let's say it was 10. I'm probably getting another CAC in three years. I'm going to be frustrated because my CAC is zero. Last three times I checked.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
If my CAC is 500, I'm probably getting a CAC next year. Because I'm going to care a lot about the progression rate for that point. The same regard with the CT angiogram. If I found that my vessel disease was pretty average for my age, I might be interested in getting another CT angiogram in say four years or five years. If it was extremely high, if I was like in the top five,
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
20% for my age, I might be getting it more frequently. The beauty of imaging is not only is it so predictive of future problems, but you can at least check into some degree as to whether or not you're making it worse much faster based on the things that you're doing. And the radiation level has now come down so much. CT angiogram used to be 10 times the radiation it is now.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
I mentioned the CAC is 0.6 millisieverts. CT angiogram for me at zero CAC was two millisieverts, which would be five mammograms, right? For reference, just a year of free living is 3.5 millisieverts, I believe. Do I feel like a takeaway that was already there for, I think, the last 10, 20, 30 years?
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
That imaging tends to be extremely predictive, extremely prognostic towards future heart disease outcomes. Yes, we reinforce that even more. But one neat thing is that this is even within a healthy population, that imaging is important to get a sense of where your heart disease risk is at right now.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Conversely, the takeaway of how much ApoB and LDL will be predictive towards my existing or future plaque, it's pretty powerful population data we have that it's not, at least at this point in time at these levels or the amount of time that they've been on a ketogenic diet.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Even though you know they're shipping a lot of the cargo because they're successful, they're moving it quickly, and the turnover is faster. So when we're seeing the high cholesterol, what we're doing is we're actually seeing empty boats Boats that started out with a lot of cargo, but are so quickly shipped and taken up by the tissues that are making use of it.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Yeah, here's a good way of me putting it. Would I be surprised that there's going to be a lot of people in your exact context that will be reconsidering their decision? Absolutely. I mean, certainly I'm being informed. for myself based on our population data as to whether or not, as to what degree the risk is. Am I more comforted?
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
I'm comfortable saying that, that yeah, I'm obviously more comforted as far as what that association is, especially for the time applied. Does that lead me to a place of complete certainty? No. And, you know, I'm not actually sure if I'll ever get to that place. Like it's even with a lot more robust data, but is this the most specific data that,
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
by far that we've had in hand yes that's where i think that there's a a pretty substantial jump that we've made with this study there's nothing anywhere close and which is a shame because we're now raising money for a new study i kind of hoped that we would just be one of 10 that these new data as they're coming out especially when we were putting out the preliminary
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
that we'd have a lot more teams that were interested in studying lean mass hypersponders. But this is the hard truth. There's just, there's not a business model to apply to it some way to, you know, you pretty much get money for research from one of two channels. You get it from the government, such as through the NIH, or you're going to be getting it through
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
some device maker, you know, for diagnostics or some kind of product such as what you can do with these numbers, pharmaceuticals, something like that. This is the only way we can do it is through crowdfunding.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
That gets us all back to this larger theme of metabolism. Because even if you're not on a low-carb diet, having, for example, high HDL cholesterol and low triglycerides tend to be associated with good metabolic health. It's just if you're powered more by carbs, you're shipping less fat. But the turnover of that cargo is still a part of the same story.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Yeah, it was super exciting. Jen Eisenhardt, who's made several other documentaries, including Fat Fiction, was the one she had done before this one. She and I got connected through Brett Scher and quite literally within a matter of weeks from us connecting, I was going to be getting that first set of scan data shown to me by Dr. Budoff.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
So me as the funder, I don't get to see things until they come to wrap up points, right? And so I was going to be seeing a summary of what the data looked like. And it was the first time all 100 scans were being analyzed. And in the course of figuring out that this was going to happen right after meeting Jen Eisenhardt, we worked out, you know what, let's get the cameras in that room.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Maybe we can turn this into a documentary. Just actually follow the entire story end to end for the study itself, at least from when the prelim data came in. So sure enough, that's when the cameras got there. You're literally capturing my reaction as it happens in real time. And eight days later, when I presented at Low Carb Denver, they were there as well.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
Pretty much, there's just multiple stops throughout all of the data getting shown to me. They're sort of the major through line of the documentary filmed over two years. But then on top of that, we did a whole bunch of interviews, which I mentioned a bit earlier. Nick's in there. Robin Dobbins is in there. There's an amazing story of a type one diabetic boy, 10 years old, super high levels of LDL.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And we got to interview Dr. Bernstein, by the way, which was a huge get for us. All of this got packed into this movie, which includes what happened when we finally got the results that were featuring in this paper and how exciting that was at the time it was occurring. It's actually a really good film.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
I mean, obviously I'm biased being the protagonist in the film, but it's really Jen and her team that made this thing so amazing. I'm really excited for it to finally get released. We think it'll be sometime in the fall.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
It'll be on a major streamer. We don't know which yet because it's being negotiated right now.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
They can go, thank you for the plug. They can go to citizensciencefoundation.org. That's quite literally the website for our charity. It is a bona fide 501c3 public charity. So your donation is tax deductible. And again, not only is this how we make it happen, but as I mentioned to you offline, we have effectively a 0% admin overhead.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
The only money that's going from somebody's donation is just for credit card processing fees or donor box, which is the major platform we work through. Last I checked, I believe we have that accounted for something a little bit above 4%. So something in the neighborhood of around 95% of every dollar we're getting is going right back out towards the research with us not taking a single penny of it.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
It's amazing because that's how we were able to get the first study done. This one's going to take a bit more money. The triad study is going to be 100 people again if I get my way for the main group, but we're also going to have a control group of another 100 people. It's going to cost quite a bit, but we're actually really close.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
I want to say we're about three-fourths of the way there last I checked.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
It's just that if you're somebody like myself or Nick Norwitz or Adrian Sotomoda, You're moving more fat because that's what you're powered by, and therefore you have more empty boats. So in a sense, what I'm saying is the LDL are just a lot of empty boats.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
That's right.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
My hope is by the time this airs, it'll actually be out. I was originally aiming for June, but because of the paper dropping, I have reason to try to launch it a little bit sooner.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
It's going to be called the Feldman Protocol.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
There's a little bit of an inside joke for people who followed me all along. That's what it used to be called when I was showcasing how I could drop my LDL cholesterol by just actually over-consuming a huge amount of fat, including saturated fat, because it was like almost a trick. But that was the initial inversion pattern that I was discussing more in 2016, 2017.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
What happened, though, was while their blood work came back looking fine, including lipids like cholesterol, mine shot through the roof. That ended up changing my whole trajectory, literally for my life for like the last decade. That's what ultimately led me to where I'm at today.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
So while the name, well, that term had kind of disappeared because I didn't want people to keep associating it with me and using it for like getting better life insurance and things like that, because that sounded prescriptive. I thought, oh, you know what? I'll see if I can bring it back for the podcast name.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And I tried that along with other names and everybody seemed to universally like that the most. So hopefully, knock on wood, hopefully by the time this gets launched. We'll have that up and going. And I'm going to try to twist your arm to show up. You come to Vegas now and then, right?
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
If you currently believe that the metric of cholesterol is in and of itself the central driver of cardiovascular disease, I often hear terms like atherosclerosis, the development of plaque in the arteries, is a disease of cholesterol, then it's understandable why you may hyper-focus on that as being the central thing to change. And all of your heart disease risk will follow suit.
Dhru Purohit Show
Is Current Thinking Around Cholesterol Outdated? What You Need to Know About Heart Health and The Root Cause of Plaque Build Up with David Feldman
And that these other risk factors are really ancillary. You know, something like blood pressure and so forth, they all come second to cholesterol.