Understanding Cholesterol Dynamics and Metabolic Health with Dr. Nick Norwitz

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Even if we assume there's always going to be risk with higher LDL particles, higher ApoB, higher LDL cholesterol. If you imagine the graph of on the x-axis LDL exposure to on the y-axis, say cardiovascular plaque accumulation, that slope of that line is going to differ based on the cause. Now, if you have a very, very steep slope, that's bad. If you have a very, very shallow slope, then maybe, you know, there's some degree of risk, but the absolute risk, if it's lower, is something that's important to, you know, it's important to recognize what the absolute risk is so you can make informed decisions on a patient-by-patient basis because every intervention has a downside.

Hello and welcome to the Dr. Jockers Functional Nutrition Podcast. The show designed to give you science-based solutions to improve your health and life. I'm Dr. David Jockers, doctor of natural medicine and creator of drjockers.com, and I'm the host of this podcast. I'm here to tell you that your body was created to heal itself, and on this show we focus on strategies you can apply today to heal and function at your best. Thanks for spending time with me. And let's go into the show. This podcast is sponsored by our friends over at Paleo Valley, and I want to tell you about their amazing super greens, organic super greens powder. And the reason why I love super greens is because of the chlorophyll content. Most people don't know a whole lot about chlorophyll, but, but it's what gives plants their green color, and it actually takes biophotons from the sun and turns them into energy within the plant. Chlorophyll is amazing for our blood purification, detoxification, and mitochondrial health. When we consume chlorophyll, it helps our mitochondria produce energy more effectively, helps our blood flow and blood pressure, uh, function more optimally, and helps oxygenate the deep tissues of our body. So it's really powerful. The problem is it's hard to eat enough plant foods to get enough chlorophyll. A lot of people really struggle. Their digestive systems really struggle to break down a lot of the plant fibers. So one of the best ways to get a clinical dose of chlorophyll is through a super greens powder. And that's why I love the Organic Super Greens, because all organic, and on top of that, there's no added sugars in it. They also have a whole bunch of other digestive supportive superfoods. They've got digestive enzymes, ginger, lemon, beet, a whole bunch of different superfoods that support digestion and have, and are rich in polyphenols that help bring down inflammation in the body and support the microbiome. And it doesn't contain any cereal grasses, wheatgrass, barley grass, oat, rye grass. There's a lot of different individuals, particularly people with chronic inflammation and autoimmune conditions that struggle with cereal grasses because they contain a compound, a lectin called wheat germ agglutinin. Which is highly inflammatory and can be very gut irritating. And so Organic Super Greens by Paleo Valley is the only greens powder that's super rich in chlorophyll but doesn't contain the WGA. So guys, you can check it out and save 15% off any of the Paleo Valley products, including their Organic Super Greens. Just go to paleovalley.com/guthealth.

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That's paleovalley.com/jockers to save 15% off. And what I do with the greens powder is I just take a scoop in water a day, every day. I usually have it after my lunch with a little bit of magnesium powder, and it is amazing. Tastes great and gives me great energy, mental clarity, supports detoxification, good blood flow, and oxygenation to really help me get everything I need from my day. So guys, check it out again, paleovalley.com/jockers. Jockers, and that will save you 15% off. Well, welcome back to the podcast. Today we've got a great topic. In fact, episode 452, I talked all about this study that was recently published in the Journal of Metabolites, January 2024. And the title of the study is Oreo cookie treatment lowers LDL cholesterol more than high-intensity statin therapy in a lean mass hyperresponder on a ketogenic diet. A Curious Crossover Experiment. And so today I'm going to actually interview the author, one of the lead authors of the study. And what he actually did, and we're going to go through it, is he had a very high cholesterol following, particularly LDL cholesterol, which most cardiologists would look at that and they would say, wow, this person needs to be on a high-dose statin medication. He was on a ketogenic diet, very good overall metabolic health, but he had this really high LDL number. And then he took 12, basically a, like a, a sheet of Oreo cookies for 16 days and then retested his blood work and his LDL cholesterol went down 72%. And then he did a 3-month washout period where he went back on the ketogenic diet, no Oreos. And then after that did his blood work again. His LDL cholesterol was up over 400, super high. And then he went on a high-dose statin medication and that lowered his cholesterol, 32%. So 70— I think it was 72% or 71% compared to 32%. So significant reduction with the Oreo cookies. And of course, we don't recommend eating Oreo cookies, and we're going to go through that today. But the— my guest is Dr. Nicholas Norwitz. He is a researcher educator whose mission is to make metabolic health mainstream. He graduated valedictorian from Dartmouth College, majoring in cell biology and biochemistry, and then completed his PhD in metabolism at the University of Oxford before attending Harvard Medical School to complete his MD. Nick's enthusiasm for the field of metabolism derives from a personal struggle with severe inflammatory bowel disease. In desperation, he found a ketogenic diet, put his disease into remission when conventional approaches failed. And so he is a researcher and also a great content creator. You guys can find his newsletter at staycuriousmetabolism.substack.com. He's got some amazing content there. He also has a great YouTube channel as well. Just look up Dr. Nicholas Norwitz, nor— N-O-R-W-I-T-Z. Some really, really good content. He's great with video editing and whatnot and very entertaining to listen to and obviously very knowledgeable. So I highly recommend him. You guys are going to really enjoy this interview. Also, please share with anybody that you know and that you care about, especially people that are on statin medications, people that, you know, perhaps are concerned about cholesterol. We go through a lot of cholesterol science here. A lot of metabolism, things that people can do to optimize their LDL to HDL ratios, LDL to triglyceride ratios, and overall just improve their overall metabolic health and their cardiovascular health. So without further ado, we'll go into the interview. Of course, leave it— leave us a 5-star review if you're listening to this. That helps us reach more people and impact more lives. Thanks so much, and let's go into the show. Well, Nick Norwitz, great to connect with you here. Big fan of your work. You got some great, great stuff going on with your YouTube channel. And obviously you, you first popped up on my radar with your study in the Journal of Metabolites. And, you know, it was obviously a captivating, captivating title there. All of us, pretty much everybody that's listened to this podcast, I mean, they, they know Oreo cookies, junk food, right? And so you see Oreo cookie treatment lowers LDL cholesterol more than high-intensity statin therapy. And of course, they, they don't even understand the next, the rest of it, which mean, which you go into in a lean mass hyper-responder on a ketogenic diet. But just the idea that Oreo cookie treatment actually lowered LDL cholesterol with somebody with elevated LDL cholesterol, which we're told is, you know, a terrible thing, right? And that's, that is, we're told that high LDL cholesterol is a really strong independent risk factor for cardiovascular disease. You were able to lower it with Oreo cookies in, in, in 2 weeks, basically 16 days. Eating 12 a day. So that was, that obviously caught my attention, read the study and some really remarkable things, just some, some the, the just understanding LDL cholesterol. This is, this is what's so key. And what I learned was that we have to really rethink how we analyze LDL. And so I'd love for you to go into, you know, your basically your, your motivation for running this study, you know, your hypothesis and then what you learned through it and Basically, you know, what, what you want to present to the lay public as a result of this study.

Yeah. Let me first provide a little bit of framing. Every time I speak about this, I try to frame it a little bit differently, see what resonates. So I'm going to start off by talking in a very boring fashion, but with a purpose. You know, when I was— I've always been a super nerd and I've always been entrenched in like jade tower academia. So the kind of thing that me and my friends would talk about over dinner which would get us excited would be like, oh, have you seen this new study in Nature about like the bile acid TUDCA and how it affects like, or is affected by BSH enzyme expression in the gut and the effects on blah, blah, blah, right? A lot of jargon. The kind of thing that if you observed two people talking about this, you'd be completely lost and you'd be like, why are they so excited? This sounds like complete jargon gibberish. But you know, as time went on, I started to study this lean mass hyperresponder phenotype, which is, which is named in the title. And I was shocked and awed shocked and awed by just how interesting this was from a physiological level. As somebody who, you know, loves to study metabolism, physiology, this phenotype to me was the equivalent of a layperson seeing an 8-foot-tall person walk into a room followed by like 12 more 8-foot-tall people. They're like, whoa, wait, this is unusual. There's something unique about this population. By understanding what's unique, we can potentially uncover a lot that's interesting about physiology in general. So that's where I was at. And me and colleagues, we had a stream of papers coming out that I think were not only interesting from a scientific perspective, or should have been interesting to the scientific community, but with profound potential implications on our understanding of lipid dynamics in humans, therefore possibly broader applications to the general public since cardiovascular disease is a leading killer, remains a leading killer despite innovations in LDL-lowering, ApoB-lowering pharmacotherapy. So we need better physiological understanding. And there's a lot of questions about cardiovascular disease that still exist. And what we have in this phenotype, which I'll explain, is an incredible natural experiment to, you know, that is an opportunity, a gift really to science and medicine to better understand lipidology, physiology, and cardiovascular disease. So I'm caught in this position of wanting to beat the drum over what I think is the importance of studying rigorously this phenotype, which we will describe in a minute. But I'm not, you know, an established researcher with multimillion-dollar grants and resources. I'm a young PhD and a medical student. And so I was in this position where I was like, all right, this discussion that I think really needs to happen is not happening. What tools do I have at my disposal? Do something maybe a little bit creative and force a discussion. That is being, we can go into this if, if you want to go into this, but I'm going to use the word silenced, which is a word with a lot of weight. And I use that weight intentionally because I think a lot of the discussion around this topic has been suppressed inappropriately, including in the peer-reviewed literature. And I can substantiate that with examples. Bottom line, here's where I was. And I envisioned this concept of, can I translate this? Can I do a metabolic demonstration that translates the shock and awe I feel to your average person. And so I envisioned Oreo versus statin, which took advantage of the physiology we understand and made a prediction based on our model that in a particular context, a particular metabolic context, carbohydrate addition, including any carbs, so quote unhealthy carbs like Oreos, should lower quote bad cholesterol. And so what I decided to do is a, a crossover study on myself where I announced before even doing the study that I was gonna do this study and my predictions. It was an a priori announcement. And the study was designed that I would eat a baseline ketogenic diet, my relatively standard diet, lock that in for a couple weeks, be getting weekly lipid tests, which my primary care physician, she was ordering, was going right into my electronic medical record in Epic. And then I would do an intervention with Oreo cookies where I just added Oreo cookies to my diet, a sleeve per day. So 12 cookies, which is about 100 grams of carbs. Then have a washout period, and then do 6 weeks of high-dose statin therapy, in particular Crestor or rosuvastatin at 20 milligrams, which is a pretty Herculean dose. It's, it's a high-dose, high-intensity statin. And my prediction was the Oreos would have a similar or possibly greater impact than the statin based on my understanding of the physiology in this context. Now that is a bold claim to predict Oreo cookies were lower cholesterol, but based on the research that we have, including other case series and an interventional trial and a meta-analysis of randomized controlled trials, I thought this would work. And because I know how to dot my i's and cross my t's, not only did I get my PCP on board, I got a highly esteemed lipidologist, William Cromwell, who trained Thomas Dayspring, who trained Peter Attia in lipids, to co-author as senior author this paper. And of course got my appropriate IRB exemption from the medical school, Harvard Medical School. I executed on the study and Lo and behold, the results showed that the Oreos lowered my cholesterol, my LDL cholesterol, the quote, bad cholesterol, twofold as much as the statin and in one-third the time. So that's the headline. And I intended it to be provocative in order to invite people to go, whoa, what's going on here? I want to learn more. Once you get past the barrier of, okay, maybe this person isn't trolling me, maybe there's something legitimate here.

Yeah, absolutely. And so you saw this big drop, 2 weeks of taking basically 100 grams of carbs. You could have done it with anything. You could have done it with eating apples, right? With sweet potatoes, right? Whatever healthy carb that you wanted. But of course the Oreos provided the provocative title and yeah, and you know, everybody, you know, no matter where you're at in the nutrition world, everybody agrees Oreos, not a healthy food, right? And everybody knows them, right? It's a household it's a household name. Yeah.

I mean, people ask me why Oreos and why not a healthy carb? That's a question I get all the time. And I'm like, well, actually we've done this with the quote healthy carbs, the fruits and the starches. We have a 2021 paper and a 2023 paper. Guess what? You don't know about them.

Why is that?

Because it's not provocative enough. So my goal was to think what is the most provocative food, carb food that this could work for? And I could not think of anything that's better branded as a typically unhealthy food that everybody knows than Oreo cookies. Which is exactly why I chose Oreo cookies.

Yeah, absolutely. So when you started the study, you were getting your LDL tested and what was it in the beginning? And then how much, you know, I know the Oreos dropped at 71%. What was, what was that drop? What did that look like?

The start LDL was 384 milligrams per deciliter, which is astronomically high. To be clear, on a mixed diet, my LDL, even on like a standard American diet, my LDL runs in the 90s. Like congenitally I have totally normal LDL. I don't have FH. When I carbohydrate restrict, my LDL goes up based on our understanding of this physiology, which we can dig into it a little bit, but just to give a little bit of background, basically if you're very lean and insulin sensitive, when you restrict carbohydrates, you have this massive shift towards fat fuel trafficking. And that can present as this lipid signature with very high LDL, very high HDL, and low triglycerides. And that triad is what we name lean mass hyperresponder. And the lean mass part doesn't come from any criteria for BMI. There's no BMI or leanness criteria. It comes from the observation that this presents in lean people, lean insulin-sensitive people, which we've actually shown in a meta-analysis of randomized controlled trials. So if you take all the low-carb randomized controlled trials and you kind of stratify them by WHO BMI criteria, The only group with increases in LDL are the lean group with BMI under 25. You have overweight or class 1 obesity, no increase in LDL. You have class 2 obesity, typically you'll see a decrease in LDL. So again, it's one of these very interesting phenomena where we're trying to understand the— sorry to use jargony terms, but the heterogeneity, the causes of like huge variations in cholesterol change that appear to be kind of a boogeyman for low carb. And we're seeing this oddity where Oh, it's not the people with metabolic syndrome, diabetes, diabetes, and obesity that are having the quote unhealthy response. It's the lean insulin sensitive people that are having these crazy spikes in LDL. But basically if you add that carbs to the system, then you can shift your metabolism towards more carb burning. And so the lipid trafficking system that results in this profile, including the high quote bad cholesterol, basically the flywheel can stop spinning. Which is why any carb should work. And in me, a pure Oreo addition should work. Now that wasn't a swap. I didn't cut out fat. In fact, I added fat and saturated fat because there's that in the Oreo.

Actually for calories in general.

Yep. I was slightly hypercaloric, you could say. I had added fat as well. Technically I had added fiber as well. But the addition of the carb was sufficient to drop my LDL from 384 to 111, which was a 71% drop. In 16 days. Now, the reason it was 16 days and not 14, because I had said initially I was going to do 2 weeks, is we were getting weekly tests, right? So the 2-week mark was supposed to be the end of that phase, but the drop was so huge that we're like, eh, I talked to my primary care physician, we're like, we probably should repeat this tomorrow and the next day to do like a triplicate just to show this isn't a fluke. Like this is a bona fide finding. So we did it on days 14 and then 15 and then 16, kind of as a triplicate. And actually the LDL was still dropping. It was still downtrending. Wow. Wow. At 16 days it might've dropped lower, but by that point I was so done with that phase that I'm like, all right, the point's been demonstrated. Let's wash out and let's go onto the statin. And to be clear, the statin had the exact effect size you would expect, a 32.5% drop. So it's not like the statin didn't work, it's just that the Oreo cookies were much more potent. Yeah, yeah.

And in the standard cardiology model where they don't really— the standard model doesn't really understand this lean mass hyperresponder physiology. And so they would look at that and they would say, that's a great drop. And they would start to try to study what is in the Oreos. Is it the chocolate? Is it the seed oils? Is it, you know, is it the artificial sweeteners? Is it the sugar?

Right.

So they would try to study it and try to understand, okay, somehow Oreos are lowering this. And that's a good response, even though you were hypercaloric. And most likely, if you were testing your insulin, your insulin probably would've been up. I'm sure it would've been up, and probably your inflammatory markers would've been up, but they still probably would've said, because they put so much of an emphasis on L total LDL particles as an independent risk factor, they probably would've said, you know what, it's worth it because it dropped that cholesterol so much.

Right. Well, that gets to, I think, one of the— or the core provocative nature of the study that goes beyond what I'm saying, which is you hear this title that has, you know, gives the impression based on the data that occurred, Oreo cookies lower LDL cholesterol more than statin therapy in this particular context. And what people immediately jump to, and I knew this would be the case, so I won't say I didn't invite it. But people need a value judgment, or a lot of people need a value judgment. They're uncomfortable sitting with cognitive dissonance. And so what you have here, because I chose Oreo cookies, is, okay, you're overeating processed sugary carbs. That can't be healthy. We just know, like, we can agree generally this is not a healthy intervention, but The response is presumed to be profoundly healthy if we assume the drop in LDL is a good thing. So you're left with this tension in your mind where you have bad intervention, good outcome. And I intentionally leave it there. That's all this is supposed to do, because you can layer over that some sort of interpretation, something like— and to be clear, I'm not saying any of this— but things like, oh, this means LDL is not bad, or this means statins are bad. None of this is said in the study, nor would I ever make these claims. And it's clear it's a metabolic demonstration, but it provokes this feeling of discomfort that forces people to try to either layer on a value judgment or do what I think is the scientific thing and say, whoa, this is interesting. What do we need to do next to learn more? Which is really the, you know, the reaction I was trying to provoke. And as for the superficial reactions, because it can kind of go either way, you know, I'll be clear, this was something I thought about a long time before doing with respect to the impacts. I think the danger of it is if people have superficial, let's say, interpretations, could it lead potentially to people making, quote, maladaptive choices with respect to managing their own cardiovascular risk? What I decided was I really didn't think anybody would be swayed, any reasonable, or just really any adult will be swayed to think, oh, Oreo cookies are healthy, therefore I'm gonna binge Oreos. Or that this would convince anybody something like, you know, LDL is not a problem. First of all, I never say that. There are gonna be people that make that statement off of it, but then I think that's more confirmation bias. So I contemplated what the reaction might be and I thought overall the net reaction will be positive. And doing an audit of the feedback, I think that's been the case. We have acquired more research partners and resources to further study this interesting phenomenon. Again, we can get into the weeds of what that is, but on the clinical end, it's very interesting. In the months that have followed the Oreo versus Statin study, it's now been what, like 5-ish months, 6-ish months? I've gotten contacted by quite a lot of physicians, including cardiologists. Who reach out, who say something to the effect of, I saw this and it provoked me to actually go down the rabbit hole with respect to this area of the literature. And I was really taken by this interesting phenomenon. And guess what? By understanding the physiology, the lipid energy model behind the lean mass hyperresponders, I actually now have a way to manage my lean mass hyperresponder patients. With an option that is not medication. So they might have patients who are medication intolerant and who are concerned about their high LDL, and they're like, well, they don't need ketogenic diets therapeutically. And now we understand the levers they can pull to manipulate their LDL. So now I have patients, say, on sweet potatoes or banana therapy, and they're having better results than they did with statins, and they're happy, and I feel more comfortable, even if we're sitting in an unknown with respect to what the risk is. We now have tools based on the physiology to apply a clinically cautious approach while the research evolves as it should. So if anything, I think conventionalists should be heartened by the fact that this provides additional tools for patients and physicians and patient-physician teams based on understanding of the physiology and the phenotype.

Yeah, that's great. Banana therapy. I love that. That idea. And so obviously Dr. William Cromwell was a coauthor on this. And so what, you know, he's pretty well known and esteemed in this world. And so what were his thoughts on, on the results of this? Did he understand this model beforehand going in, or was this kind of a new insight for him?

I approached Professor Cromwell for a few reasons. The chief among those was that Dave Feldman, who is the, you know, original, well, let's just say the lipid energy model and the lean mass hyper-responder phenotype were originally his brain babies. Yeah. He first observed the phenotype back in 2017 when he hypothesized its existence. And he had talked to Professor Cromwell before, and Professor Cromwell was someone who stood out as, you know, an eminent and respected person in the lipidology field who was o— also very humble and open-minded with respect to new ideas. And somebody that, like, when you sit and talk to him, you can tell he's genuinely a lifelong learner, not just paying lip service to it, but like really open to new ideas and willing to come to the table with us and have an open discussion and help us speak about this in the appropriate manner, which I think is to project scientific enthusiasm while caveating it with appropriate clinical cautions. And basically projecting the idea that like, this is scientifically interesting, but in the absence of more information about this, we need to, first of all, make this a research priority, but also not read into the data things that aren't there. And the thing is, we're saying this all the time, but sometimes it's not just what is being said, but who is saying it. So he has been an excellent partner and advocate for our work. And in general, I think he is very open and taken by the lipid energy model to the extent that it is, you know, an existing hypothesis. But we all agree it's one of those things that's like this idea we have and we can test it in bold, provocative manner like Oreo versus statin and like the predictions bear out. But to properly prove this model, we need better studies. But to do those better studies, honestly, we need more partners and millions of dollars. And I don't have millions of dollars unfortunately.

So yeah, yeah, sure.

This is a very early stage of the, the research development.

Yeah. More, the more information, the more data you get like this though, the more it's going to, it's going to bring up the demand for that sort of research.

Right.

And so let's go into the lipid energy model and the lean mass hyper-responder. So lean mass hyper-responder, I'm actually one of them as well. It's a very lean individual, right? So they're, they're low in body fat. And they get blood work done, they, they tend to be very active if they're on a low-carb diet. Doesn't happen if they're just eating a, a mixed diet or any sort of diet. But if they're on a low-carb ketogenic style diet and you test their lipids, their LDL typically is gonna be up over 200 and sometimes like you, you said 300, 400, the HDL is typically up over 80 and triglycerides are usually under 80. So it's usually they have more HDL particles than triglycerides. Typically, or at least a 1:1. Yeah. Is that, is that pretty much describe the lean mass hyperresponder?

So we have 3 cut points, the LDL over 200 milligrams per deciliter, HDL cholesterol, not the particles, over 80 milligrams per deciliter, then triglycerides under 70.

Under 70. Yeah.

Per deciliter. So I mean, people ask why these cut points. I mean, why any cut points in medicine and physiology? You need to create cut points in order to kind of parse out a, you know, a unique phenotype. So at some level they're arbitrarily drawn. I like to say like physiology doesn't care about the cut points that we create, but we do create them in general in medicine to categorize people. So the union of these 3 cut points will be extremely rare outside lean low-carb people. So that's why those cut points exist. And those 3 cut points, just to reemphasize, they're the only criteria for lean mass hyperresponders. And then the leanness factor comes in because this triad tends to emerge in lean people. Theoretically, you could have a quote, lean mass hyper-responder with a BMI of 40. I've just never seen it before.

Yeah.

Because this, this tends to occur in lean insulin-sensitive people vis-à-vis the lipid energy model.

I would be interested to see what the, I know it hasn't been, been looked at, I guess, in detail, but also adding in a fasting insulin and seeing what the fasting insulin levels look like if there's some sort of cutoff.

I'd be astonished if it weren't very low fasting insulin. Yeah. I mean, mine typically runs below 3. Yeah, right. Which I think would be typical. And BMI in the studies tends to be an average, just so people know, like around 22. Yeah. In the cohorts we looked at. So, you know, quite lean as compared to the average population.

And I think that's why, like, I mean, people that with a BMI up over 40, unless they are, you know, like an autoimmune diabetic, they're gonna have very high insulin, right? And so I think that that could also help kind of trigger the, you know, kind of adding that in as a criteria point could help with defining it, you know what I mean? From, from the lean perspective, right? We all, we know they're insulin sensitive, right? We know these individuals are insulin sensitive. It's just a matter of adding that extra data point in there.

Right? So just to be like, historically, basically this, this, these criteria emerged from an empiric observation by Dave Feldman in 2017 prior to any data. And then like with a lot of things, it just gets solidified in the literature. Yeah. Because, you know, you, you define a phenotype and then you start to study that phenotype. Now one could then refine the criteria down the line and just to kind of give people a sneak peek into what we want to do next is really try to identify what factors predict who would convert to lean mass hyper-responder and then associate with conversion, which the best way to do this ideally is prospectively where we take a bunch of people, maybe starting with very lean people, and we put them on carbohydrate-restricted diets and then see who converts and what is special about those people who convert. And the ideal, my ideal setting is to do this with longitudinal multiomics, which multiomics means all the omics. So genome, microbiome, proteome, transcriptome. And what you can do with certain labs and certain technologies is take these multiomic profiles at different cut points. In people and basically get this high-resolution video of what's going on metabolically in a person. So that would be ideal because then we could really define, you know, what is going on physiologically in lean mass hyperresponders and why does this lipid triad tend to emerge in some people and not others? BMI is a very, very crude predictor. Yeah, it's a pretty good predictor, all things considered, I mean, like, just to give you a sense of scale, you know, lower BMI, just a normal BMI, normal, basically lean BMI under 25 is as a categorical variable over 5 times as strong as top quartile saturated fat intake for predicting LDL rise in low-carb diets. That's pulling out of our meta-analysis randomized controlled trial. So BMI is a decent predictor. It doesn't mean we couldn't do better. I'd love huge population, you know, data with like DEXA scans and multiomics and this, that, and the other. Again, we're at the beginning of this journey.

Yeah, that makes sense. And you know, as somebody that's used a ketogenic diet therapeutically, not only for myself but also for clients, you know, I used to see clients for 12 years and I was using this as one of my tools. I wrote a book about it and I would see, you know, some of these individuals, right? And they, LDL cholesterol really high, but health outcomes great. And they would be like, you know, my doctor had said everything's good except my LDL. He wants me to start on a statin. And so for me being, being a functional medicine doctor and kind of having a skepticism of mainstream medicine to begin with, I'm like, he doesn't know what he is talking about. You know, LDL, right? And I, I would say, you know, I would just kind of throw it out like, ah, that's not, that's not a good risk. You know, it's not a good independent risk factor. But I didn't understand the physiology of why, why is it elevating? I would just be like, your inflammatory markers are down. This is good. This is a positive response. Response. So I wouldn't worry about it. And so the lipid energy model really helps us understand more about this. And can you go into a little bit more detail of how to understand LDL? Because most people, when they think about LDL cholesterol, they just think of like this waxy substance that's in our bloodstream that ends up getting into the arterial beds, creates inflammation that clogs our arteries, right? And that's really all they know about it.

So I'm gonna put a pin in a topic that I wanna return to. Which is separating the physiology from the risk profile. And also the idea that just because something's adaptive, it means it's safe. So yeah, we'll get to that in a minute, but I will answer your question and explain the lipid energy model, which is a physiological metabolic explanation for why lean mass hyperresponders manifest. And basically the idea is if you have a lean insulin sensitive person, when they go low carb, and the carb stores in their liver drop, they really shift rapidly towards fat fuel trafficking, which means fatty acids are released from their adipocytes, their fat cells. So your fat cells are spilling out fatty acids, which in fasting and carbohydrate restriction occurs more in lean people. That's already known. And your muscle tissue will like locally gobble up the fat cells. They get fuel, but there's a lot of fatty acids circulating around. So what ends up happening with those is they go back to the liver and the liver takes them up. And the liver will repackage these fatty acids by, you know, appending 3 to a glycerol backbone. So you end up with this like M-shaped molecule. It's a storage form of fat called triglycerides. And those triglycerides, they're fatty. Fat doesn't mix with water, right? So you need a way to traffic them around the body, get them back to the fat cells to replenish the fat cells and to muscle cells to continue to fuel muscle cells. So you take these triglycerides and you package them on triglyceride-rich lipoproteins. The main one being exported from the liver is called very low density lipoprotein, VLDL. So you package these big spheres, kind of like boats trafficking the triglycerides. You package these VLDL with triglycerides, they get shipped out of the liver. Then what happens is these big VLDL will go back to fat tissue and muscle tissue where the triglycerides in their center will be sucked out by lipoprotein lipase. So this enzyme that breaks down the triglycerides so the fatty acids can go back into the fat tissue and into muscle tissue. And so it's really this process of the VLDL packed with triglycerides getting exported at a much higher rate to replenish fat cells and, and fuel muscle cells coupled with the turnover of the short-lived VLDL so that the VLDL is getting turned over, the triglycerides are getting sucked out rapidly, right? So let's think about the triad. Triglycerides getting sucked out rapidly to replenish fat cells and fuel muscle tissue. So the triglycerides are gonna go down. Okay, one point of the triad, low triglycerides. What happens when you shrink the VLDL? It becomes an LDL, which sticks around longer. The VLDL is short-lived, the LDL are longer-lived. So you're left over with more LDL. So LDL is high, point two of the triad. The last point of the triad is the HDL, and HDL cholesterol goes up in lean mass hyperresponders because when you shrink the VLDL, The triglycerides get sucked out, the VLDL becomes a smaller LDL. Well, when you shrink a sphere, you need to shrink its surface area. And there are surface components including cholesterol that get kind of taken off and taken up by acceptor particles, which are HDL particles. And so the, um, amount of cholesterol in your HDL goes up. So you're left with this triad of the high LDL, the high HDL, and the low triglycerides. That is the lean mass hyper-responder phenotype. And this all occurs because of a shift in fuel demand from carbs to fat and the spinning of this flywheel that is the lipid energy model. So that's our physiologic understanding. And by understanding that model, or let's even call it a hypothesis, it's both, but you know, we can use the more humble term. You can make predictions using this hypothesis. And one of those would be say adding back carbs. Should stop the flywheel. LDL goes down. We see that. Or increasing exercise, cardiovascular exercise, then you need more energy, should increase the flywheel. Does LDL go up? Yeah, we see that too. There are different ways to intervene in order to test the predictions of this model. And thus far, even the boldest predictions like Oreo cookie addition to your diet have proven to be, or have borne out to be consistent with the model. So that's the model. I'll pause for questions, then I want to talk about what the model means and does not mean with respect to risk, cuz I think it's important to caveat.

Yeah, that's a great explanation. And you know, to add in, and this is a hypothesis, is that insulin is like the key lever. So like when insulin is beyond a certain threshold in certain individuals, so if it's above the threshold, they're not, their fat burning is lowered, right? Cuz it helps block lipolysis or the breakdown of fatty acids for fuel. And when it gets below a certain threshold, in, in a sense, it, it kind of takes its foot off the brake and now the body's just going into higher degree of fat burning. And so that, so we just don't know where kind of that, that threshold is. And it, it could be unique for each individual. Like we don't even know if there's an actual set point, but we do know that these individuals have very low insulin like you were, you were talking about.

Yeah, I would say that a question that arises that I haven't fully answered is, oh, but why in lean insulin sensitive people does this manifest and not in people people with obesity. What I can say is this is certainly consistent with the literature that exists, which we go through in the lipid energy model paper, which if you can feel free to link in the, yeah, the podcast notes. So it's consistent with clinical data, say in lean people versus people with obesity in fasting and carbohydrate restriction. We don't know the exact profile metabolically. What is the hormonal milieu that permits this to occur? And I think one key ingredient in the hormone soup, so to speak, is insulin. So you're right, if insulin is high, you're kind of gonna put a lock on liberating free fatty acids, which, you know, occurs at the beginning of the lipid energy model cycle if you wanna add a beginning. So I do think if someone's insulin resistant and hyperinsulinemic, then it, you know, does provide an inhibition to the lipid energy model Moving forward. But that doesn't mean that low insulin is sufficient for the lipid energy model, right? To manifest. But I would, I'd be surprised if it wasn't necessary to some extent. Low insulin.

Yeah, I was, yeah, low insulin and then probably enough, I guess enough dietary fat. Well, of course with fasting it goes up too.

So it's not, no, you don't need dietary fat. My LDL will go up with just fasting. So if you're taking in zero fat, in fact Sean Baker did this where he like, he's not a lean mass hyper-responder, but the physiology, again, like physiology doesn't care about the cut points. The physiology can still be applied. So, you know, if Sean Baker like fasts and then does a workout, his LDL will skyrocket. I think it went from like the 100s to like his total, his, his total cholesterol. I don't quote me on this, but I think it was like around 150. We were talking about this the other day. And if he fasts and does a workout, like in a couple days it can jump to over 300, right? So just showing that like these are dynamic shifts. Yeah. And probably to meet fuel demand.

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Yeah, I think this is where it's hard to communicate the nuances without people having a degree of background because there's a lot of jargon we use, things like necessary, sufficient, causal, and they all tend to get confused. One point I would like to make that I do think gets confused a lot on social media is we can talk about LDL particles and LDL cholesterol is kind of a weak man's proxy for the LDL particles. You mentioned ApoB. Yeah, ApoB is the apolipoprotein on LDL particles. So it's similar to the LDL particle count, although there's ApoB on some other particles like VLDL and Lp, another topic. But bottom line, I would say the literature does show, and people get defensive about this comment, but that it is causal. As in it's part of the causal cascade. So if you don't have LDL particles, you won't get ASCVD. But just because something's causal doesn't mean it is a large magnitude predictor relative to other things. And just because something else is not causal doesn't mean it's not relevant to look at. So things like, you know, the high triglycerides and the low HDL, even if triglycerides and HDL aren't causal, the patterns that we see can be predictive of outcomes. I think what is often missed is people like to take a, a tunnel vision focus on a marker often because, I mean, it's easier to target that marker. We have drugs that can just target LDL, target ApoB, and so they become the, the narrow focus. But what we really care about with respect to metabolic disease and cardiovascular disease is, and metabolic disease is what is the root cause physiology? What's going on with respect to metabolism? Because if we wanna treat it, we should address root cause. And that root cause, or what's going on, let's say metabolically in an individual, can be intuited. We can gain some insight by not looking at single markers, but looking at patterns of markers. And this isn't specific just to say LDL, but a topic we were talking about in associations is a whole different rabbit hole. People can see my video on this if they want to look at metabolic vulnerability. But one thing we talked about, me and Professor Cromwell, if you really wanna deep dive on that, you can listen to the 5-hour podcast I have with Simon Hill, is that like there's a multi-marker, this metabolic vulnerability score. Now each of the components aren't necessarily causal, but you combine them and what you get is a signature that suggests something that is going on under the surface. So I know that was a lot of words and rambling, but I do want to dissect that something can be causal and maybe not the most important thing in the world, and something else can not be causal and actually be very informative. Is that point clear? 'Cause I have like 12 other points I wanna— Yeah, yeah.

I think that's, I think that's clear. I think what you're saying is that LDL particle is still an important, an important biomarker to look at. However, you have to look at it in the overall metabolic signature, meaning looking at it in proportion to, you know, a number of different other biomarkers like triglycerides, HDL, you know, perhaps a fasting insulin, right? Inflammatory markers, some, some things like that that could give you a better, you know, just a more in-depth and nuanced understanding of, of what's happening in this person's body.

Right. Because cause matters, right? Like not all high LDL is equal, you know, in, in general, in, in medicine, like not all, name your variable X as equal. The analogy I often go to is like, you know, if somebody's 6'5" because they have tall parents, okay, they're 6'5" because they have tall parents. They could also be 6'5" because they have, you know, a brain tumor secreting growth hormone and gigantism. Those are two very different causes for the same outcome with respect to one marker, but they're gonna have different results. And so it's the same with LDL where context matters. What is your metabolic health status, other contexts like other family history, genotypic risk, and what is going on physiologically to drive up your LDL. And this isn't controversial. This has been published, say, in JAMA Cardiology, where they look at people with similar LDL levels but from different causes, say polygenic FH or familial hypercholesterolemia. I'll try to avoid the acronyms, or monogenetic, or no known genetic cause. And Despite similar LDL levels, they do have different risk profiles. And so what we have here in lean mass hyperresponders is a population unlike that we've ever seen before. So it's inappropriate to conclude we know what the absolute risk profile is in this context because it's a different context. There's a different underlying physiologic driver. That's very clear. And so the question, what is the risk profile? The answer is a big fat, we don't know. Another way to think about this, if people are mathematically minded, is even if we assume there's always going to be risk with higher LDL particles, higher ApoB, higher LDL cholesterol, if you imagine the graph of on the x-axis LDL exposure to on the y-axis, say cardiovascular plaque accumulation, that slope of that line is going to differ based on the cause. Now, if you have a very, very steep slope, that's bad. If you have a very, very shallow slope, then maybe, you know, there's some degree of risk. But the absolute risk, if it's lower, is something that's important to, you know, it's important to recognize what the absolute risk is so you can make informed decisions on a patient-by-patient basis, because every intervention has a downside. So this isn't like LDL denialism or anything. This is asking appropriate questions. I'm not saying lean mass hyperresponders are a safe phenotype with respect to cardiovascular health. I'm saying we don't know the absolute risk profile. Mm-hmm. And it's appropriate to ask the question, what is the risk profile in this unique phenotype that is understudied?

Yeah, that's good. It's a totally new population because all the cholesterol research has been done on people eating higher carbohydrate diets cuz that's what we had in the 1900s and early 2000s. Ketogenic diet or low carb style nutrition really hasn't been— wasn't really promoted until, you know, really in the last 15 years or so. So, so it's a new population group that we need to understand more about. Now, also, when it comes to LDL, there's different types of LDL, right? You have your small LDL, which, you know, they say small dense LDL, and then you have your larger LDL pattern A, which is your large fluffy LDL, and you've got your small LDL, which again, they call it dense LDL, which the small dense are, have more of an atherosclerotic risk factor with them. And they're associated with higher insulin levels as well. And so most of the time when we're running a lipid, just a, a standard lipid panel, we don't know what kind of LDL they have. We can make assumptions based on their triglyceride HDL ratio. If that's, if that's low, we tend, tend to think, okay, this is more of a pattern A, a healthy large fluffy. And if it's high, if they have high triglycerides, low HDL, we tend to think small dense. But without getting more in-depth, you know, understanding, you know, more in-depth testing on the LDL, we don't really understand what type of particle is there.

Yeah.

And how does that play a role here?

I would say, first of all, I want to acknowledge there is controversy over the claim that small dense LDL is less atherogenic and big fluffy is safe. And I think There are a few reasons for the controversy, but even without staking a claim on whether or not that's true, what I would say is coming back to the idea of, of profiles, what we can say is somebody has a quote, pattern B phenotype, again, being very categorical. And that means a lot of small dense LDL, which couples with high triglycerides, low HDL. All those things are metabolic signatures about something that's going on physiologically. So with the small dense LDL, you probably have impaired LDL clearance. To some extent, right? So it speaks to, again, what's going on metabolically, physiologically. And these are all covariates which make the literature, let's just say, a little messy. And there's mathematical modeling you can kind of do to dissect it. But I think the best way to dissect it would be to isolate out different variables and phenotypes. And again, what we have in lean mass hyperresponder is something unique, which actually brings me to a statement that I, I wanna put out there because people will hear it all the time. What, what do you think, David, when I say the preponderance of evidence? You wanna explain to people like why doctors say that and what they mean by the quote preponderance of evidence?

Yeah, when I hear that, I would think that if you were to take the overall amount of evidence, the majority of it is pointing in a certain direction.

Right. So this is a— I don't want to say virtue signaling term because I think it's an appropriate term used in particular contexts. But with respect to what we're studying now, something that people will say, again, just kind of the vernacular of medicine is the preponderance of evidence says X, Y, Z. And the point that's trying to be made is, look, no one study changes a field, or very rarely does one study change a field. So for example, we're going to have the first ever study that gives some insight potentially into risk in lean mass hyperresponders. It's already been accepted. I looked at the author's proof, it's coming out in Jack Advances. It probably will be out by the time this podcast drops. And it is not consistent with the idea that lean mass hyperresponders are a high-risk profile. Now they're very preliminary data. I don't think they should or will change clinical management at this time, but I know what's gonna happen is, and this has already happened, so that's why I know, is people will say, Well, these data are preliminary and the preponderance of evidence says XYZ, basically saying, look, you have this new data, don't overinterpret it because we have this huge body of literature built over decades from teams across the world, reputable researchers, esteemed cardiologists, lipidologists, that says what appears to be otherwise. That sounds like a nice comeback. The issue is the preponderance of evidence is handicapped by the populations from which it's drawn, because the preponderance of evidence is going to be pertinent to the populations off of which it was built. So if you have a completely new population, then what is the relevance of the preponderance of evidence? Let's just— I'm not going to say it has no relevance, but it's severely handicapped. And I think new populations require, you know, dissecting out those populations in order to understand what's going on with them and the risk profile associated with that unique population.

Yeah, it's so key to understand that. And how did you, so as a researcher, you said you follow a ketogenic diet, ketogenic style diet on a regular basis. Why, why have you decided that that is the diet and lifestyle that, that you, you personally practice?

When I was finishing college and then when I was beginning my PhD, I had pretty crippling ulcerative colitis. Like bloody diarrhea 20 times a day in the ICU in palliative care. I had gone from, you know, in the timeframe of a couple of years over my disease's development being like a obviously quite academic, like vibrant young athlete. Like I was running sub-3 marathons. I held a couple of push-up records. Like I was in life. And then I went to that to being a socially withdrawn, you know, psychologically, like, tortured, and, you know, academically doggy-paddling individual who was just trying to, like, get through life. And it was this place for me where it seemed outwardly, if you just kind of knew what I was on paper, oh, this, this kid has life laid out for him on a silver platter. I had a position at Harvard Medical School locked in. I had my PhD position at Oxford. I just graduated an Ivy League college. Valedictorian, everything seemed nice, but I was in a hospital bed with brain fog, wasted away to like 100 pounds, 100 pounds with like bradycardia into the 20s, unable to basically do anything. Like getting outta bed was an effort. And so I got to a point of desperation where I was just trying a bunch of different things. I eventually tried a ketogenic diet after many other diets and it was the only thing that ever worked for me. And I've been in remission, actually biopsy proven remission now for 5 years. So it's enabling me to live my life. But after I adopted the ketogenic diet, this phenotype emerged in me. This is before the phenotype was documented in the literature, but it emerged in me. And so, you know, if I were in a place to just have a sweet potato and reduce my, reduce my presumed risk, great. I love sweet potatoes. Probably put some figs on there, maybe a little bit of honey, some goat cheese. It'd be delicious.

Yeah.

And then I'd live with an LDL of 90 rather than, you know, It's been above— the highest it's been is 545. But the fact of the matter is, for me, a ketogenic diet's therapeutic. And I've tried ezetimibe, I've tried Crestor. I've had side effects with both. There are other medications that I can take. This isn't about the Nick, you know, Medication Decision Hour. A lot of thought and a lot of conversations between me and physicians have gone into my personal decision-making. Right now, candidly, I am in a wait-and-monitor period. I've had coronary CT angiography scans. My scan, singular, and my arteries are right now clear. So I, the way I think of it is I have a little buffer room to see how this literature develops. And so currently I'm not taking medication, but you know, I wanna make clear my decision should not translate to your decision. And I'm, I'm constantly very open-minded and, and, and reevaluating that choice. So I could change my decision tomorrow. This is not something I have, you know, the utmost confidence in with respect to my own health choices. And I don't think people should gamble with their health, which reminds me, I wanted to make a point about the lipid energy model, which was, it's a metabolic physiological explanation for why the lean mass hyper-responder phenotype occurs. And sometimes people make the logical leap that, oh, it's normal physiology and quote natural, therefore it's safe. That is not an appropriate extrapolation. We can ask the question, what is the absolute risk profile? And say it's unknown. That's fair. But it's not fair to just say, just because something is adaptive acutely, that it's safe in the long term. So I think often these two topics get mixed when we're talking about the physiology and the acute response and the lipid dynamics and then the risk profile. And I wanna say, obviously they're related, but they're not overlapping. So scientifically, I find the lipid energy model fascinating, but I don't think it necessarily implies a low-risk profile. So you can see I'm struggling with how to parse out all these nuances like natural versus, you know, risk profile, asking the question what is the absolute risk versus the false claim that we know this is a low-risk profile. But really, if people are to appropriately approach this topic. Like, we do need to be very precise about how we're talking about these things. And right now where I am with this is I'd prefer to give people the benefit of the doubt and try to explain the nuance to them rather than patronize them and say, you know, this is too complicated, lower is better, take a pill. Because I feel like that's where a lot of the field is. And having been a patient that was patronized too, I know how crappy that feels. So I, I try not to propagate that. So anyway, yeah, if people excuse, I apologize, but that's what I'm trying to do.

Yeah, that's good. Now you said you had side effects when you've taken statin drugs. What kind of side effects have you noticed?

The statin was pretty mild. It was a, some myalgias, which are basically muscle pains associated with a little bit of a bump in CPK. So a, a muscle marker damage. Yeah. To be clear, the bump was— it was very mild. Like I was just above the normal range. It wasn't like I was having rhabdomyolysis or anything like that.

Yeah.

And but the combination of the myalgias with the bump in CPK with, you know, the benefits being unknown were sufficient for me to stop the medication at that time. To be clear, this was also on the OREO versus statins study. When I was taking 20 mg, which is a high dose of Crestor. Yeah, true. So it's possible I wouldn't have had acute side effects on a lower dose and might've gotten some therapeutic benefit. There are also drugs I haven't tried like PCSK9 inhibitors or bempedoic acid. So there are other options on the, the pill buffet open to me.

How about any fatigue? Because if we understand the lipid energy model, if your body's really trying to burn fat for fuel and we're limiting the amount of buses carrying the triglycerides Are we though to the cell?

Are we? I mean, so this is a really interesting question. This is one of the, the studies I want to do because you're right. If we said we are limiting fat fuel trafficking, then you should be able to detect that with respect to even performance outcome metrics. Yeah. So we do like VO2 max tests, exhaustion tests, and lean mass hyperresponders. However, what you don't know from a standing lipid test. You get like a snapshot of what is circulating in the blood in terms of LDL cholesterol, even particles. That doesn't actually tell you about flux. So how do statins work? They inhibit HMG-CoA reductase, and as kind of in part a compensation by the liver, the LDL receptors on the liver go up. So you end up having more LDL particles pulled out of circulation. So if you took a statin and there's more LDL receptors and you're pulling more LDL particles out of circulation, the system could adapt by exporting more VLDL, having, you know, continue to have turnover, but you're getting more LDL pulled out. You'd still see a drop in LDL like I did, but you might have sufficient flux such that you can maintain energy output or at least the decrement will be so minimal that would be very hard to detect in terms of clinical outcomes or a VO2 max test. Maybe you could, but you need a tremendously high-powered study. So you might end up getting what you could say is a false negative. However, I would predict, I think it would be fair to predict if you put somebody like on triple therapy, like you give 'em ezetimibe, PCSK9 inhibitor, and a statin, and you take a lean mass hyperresponder and pharmacologically tank their LDL, to like 20, then I do think that would be enough that there would probably be insufficient flux to meet fuel trafficking demands and you would see a decrement in performance.

So your, your hypothesis is there's kind of a point where their body's just not gonna be able to overcome and adapt.

Yes.

I think that's very possible. I think it's a really cool study. Like if we did this study properly, it could be New England Journal level. Yeah, because it would be such an incredible demonstration.

Not sure who wants to volunteer for that one, but you could find—

I mean, maybe we could find volunteers, but I mean, honestly, what we would need— yeah, that's— maybe we couldn't find— I don't know. It would be a very fun study to run if I could clone myself and just get like me. We would do it, but, uh, you know, again, it would also require resources, the right research team. But I have a list of studies I want to do and That one will be a very, very cool study. And I, I honestly don't know what the results would be, but that's kind of how I think about where, yeah, you're right in theory, but it's a little bit more complex than just give any dose of a statin and we would, we should see an effect. You'd really need to get above a certain threshold, I think, to be likely to see an effect on function. But you could, and a lipid energy model would predict that.

Right, right. Well, this has been a really fascinating discussion and I'd love to have you back on. In the future we'll talk about, I know you recently published a great video on satiety per calorie issues and how the, in a sense, the food industry is using that to market processed foods as, you know, with their scoring sheet as more beneficial than, than real foods, right? And interesting, it's an interesting idea. Did, did you wanna say something about that?

I would say that might not be the steelman case for the, yeah. People that are pushing forward the idea. We don't need to go into the nitty-gritty because I realize your, your, your time is coming to an end. But I would say people can go check out that video if it's still up. I'll be clear, actually, the first comment on the video notes, in case you don't find the video, is I want to delete this video and I will do so if— because you can tell probably even from this discussion or just knowing me as the Oreo Doctor, that I don't mind being provocative, but I'm always very mindfully provocative and provocative with a purpose. So in this case, this is a response video that I am doing to a particular group, and it is something I've been sitting on for quite a lot of time. And I'm not just trolling for trolling's sake. So I actually, I go through what I consider is, I project it as a case study in manipulative marketing where something is presented as science. And I, I present the steelman case up front. Like, look at how enticing this is. Doesn't this seem reasonable? But actually, and then start to unpack it a little bit as a case study in marketing, which I tried to pull value out of it. But at the end, I make very clear, look, I just want the company to step up and do the right thing by the intellectual integrity, by the science. So if they can do any of these, and I give them a list of 4 things which are pretty low bars, you watch the video, one is just being like more intellectually honest about their, their marketing and a little bit more humble about their absurd claims. Then I'll remove the video. I'll remove the video, I'll remove the tweets, all the social media around it. I'm not doing this just for attention, but because I actually think it has the potential to be harmful and it's a useful teaching tool.

Yeah, that idea of satiety per calorie. We know, we know that not all calories are the same. The calorie you get from, you know, a piece of broccoli, right, versus a calorie you get from canola oil, it's not gonna impact your body in the same way. And there's gonna be a level, or, or sugar in general, right? And so, but there's gotta be a good way of really analyzing that satiety per calorie. And, and that's, that's what you're, you're calling out.

I'm calling out what I think had the potential to be a good idea that was terribly executed, terribly executed from a scientific perspective. From a marketing perspective, actually, it's kind of brilliant.

Definitely.

And I wanna parse those intentions because, you know, that, that idea of focusing on what makes you full for fewer calories is a fine heuristic.

Yeah.

There's nothing wrong with that as it, like, as a heuristic, as a mental hook. I'm not against it and actually think it could be executed quite well. But what ended up happening is they created a scoring system that was very manipulative that they're presenting as like the universal model of obesity. And then basically what spins out of it is this stream of absurd claims, quantified claims. Like, you know, they'll put out a tweet, what is the best ice cream for metabolic health? And they'll rank something like Halo Top. Ice cream or Arctic, you know, peanut butter chocolate chip diet ice cream is like better than avocados, better than olives. They throw nuts under the bus like dark chocolate is terrible, all these things. And it's like, look, this is just disingenuous. And I actually do think it— well, anyway, I won't—

a lot of these models should make intuitive sense and that just doesn't make intuitive sense there.

Right. And then, but then the layer on top of that is there's a marketing playbook you can use to defuse criticisms towards that end. It's like, oh, this is, you know, we're tweaking things as we go. Like, there are virtue signaling defenses that you can use that work really well on social media. And that's what I try to parse out is like, what is the playbook that this company is using, which actually gets used by tons of companies. And it's things like, you know, virtue signaling around diet agnosticism. It's like, you don't need to be in a diet cult. Let me tell you, you know, XYZ. So if you get nothing else out of the video, I think it's, and you don't know what Study Per Calorie is, I think it's a good case study. And this is the marketing ploys people try to use and then you can be on the lookout for them. And some of 'em are pretty insidious, like flipping the burden of proof and logical fallacies that like the average person wouldn't pick up on because they sound fair when you see them in action until you learn what's going on. And then you see this psychological hack. And then you can't unsee it. You'll see it everywhere in life. So yeah, yeah, people can see that video and my other content sometimes. I often just like to break down the science, but every now and then, for sure.

Well, let's touch base in a month or so and see if you still have the video up. And if so, we'll touch base and do another interview and we'll go in more depth there. But in the meantime, guys, check out Nick Norwitz. You can find him on Dr. Nick Norwitz on YouTube, on his Instagram as well. Nick Norwitz, PhD. He's on Twitter as well, and his newsletter, which is a Substack, staycuriousmetabolism.substack.com. We'll have all that in the show notes as well as the Journal of Metabolites study that we discussed a lot today. Nick, again, thanks so much for your time. Really appreciate you and look forward to having you on again in the future.

Thank you so much.

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