Reactions to Oreo Versus Statin Study

I've gotten a lot of requests for an update video on my Oreo versus statin study. People are asking, you know, how are people responding? Do you think it had a positive impact or a negative impact? What's coming next? Now, this video isn't gonna be about the study itself, which I'm kind of assuming some background knowledge on, although I will give a very, very high-level overview now. This was a study in which I pitted Oreo cookies, yes, a sleeve of Oreo cookies added onto my diet, to 6 weeks of high-dose and high-intensity statin therapy for lowering my LDL in a crossover study on myself, a lean mass hyper-responder. The hypothesis was that according to our lipid energy model, I should be able to reduce my LDL cholesterol with any carb, including adding Oreo cookies to my diet, and this would have a similar or potentially greater effect than high-intensity statin therapy. Statins being standard of care for high LDL. Now, to my surprise, not only did the Oreos work better than the statin, they worked faster and were 2 times as potent. The Oreos reduced my LDL from 384 to 111 in 16 days, with a reduction of 71% in LDL in 16 days, compared to a 32.5% reduction on the statin. So the Oreos blew the statin out of the water. And it surprised a lot of people. Honestly, the magnitude of the effect surprised me too. Now, since I published that, there's obviously been a lot of discussion. The whole point was productive provocation to get people to turn their heads and look at not Oreo cookies, but the whole body of literature around lean mass hyperresponders and the lipid-energy model, which I think are so, so important. And people have been wondering, what has the response been? That's what this video is going to be about. I hope you stick around because I think it's an important discussion to have. Welcome to my channel. Stay curious. So first, a statistic. One way you can actually measure impact, media impact, of a paper is something called an altmetric score. And the altmetric score for this Oreo versus statin study is 1,931, which puts it in the top 0.02% of all 25,700,000 papers ever tracked. It's about 15 to 20 times higher than your average Nature or New England Journal paper. So people are definitely talking about it. Um, but statistics aside, because that probably doesn't matter to a lot of you, what have the response been behind closed doors within Jade Tower academia? Because that's honestly probably what matters more than the social media discussion, which has a different leaning, let's say, generally is more controversial. I have been really heartened to see how my peers, my peer medical students, medical students at other institutions, senior residents and senior attendings have been responding to Ori Overstatin. Yes, of course, the word has gotten around at Harvard and elsewhere, and overwhelmingly The response is pure curiosity. Ironically, I'm wearing that shirt. Stay curious. People in academia— the academia is selecting for the right people— are by nature curious. And this is something that is a curiosity. You know, when we have a patient that comes in that doesn't fit the mold that we've been taught to look at for exams like Step 1, Step 2, you know, your medical horses, so to speak— when a clear medical zebra comes through, we want to look at it and learn about What's different about this patient and what can I learn about this case? Because those are the cases that have the most to teach us. And it's the same with Oreo versus statin. This is a bizarre response, but the one that was predicted by our model and is consistent actually with other literature showing carb reintroduction can massively lower LDL in lean mass hyperresponders. We have a case series showing that, and we have an interventional trial showing that, which preceded the Oreo versus statin study. Nevertheless, the Oreo bit is kind of shocking. That's why I used Oreo in the first place, to say, look, this isn't about healthy carbs, this is just about putting carbs in the system, removing a driving force behind the lipid energy model, therefore reducing the flywheel of the lipid energy model and bringing down LDL. Again, the lipid energy model isn't the topic of this video. This is about reaction to the phenomenon, especially when people were naive to the lipid energy model. So I have peers coming to me and patting me on the back and wanting to learn more about lean mass hyperresponders and the lipid energy model and basic physiology. We'll sit down over a coffee, maybe a butter coffee, just kidding, and discuss the mechanisms of lipid energy model, how VLDL is exported and turned over by lipoprotein lipase, how this generates lean mass hyperresponder triad, and also what is known and what is unknown about the mechanisms and consequences of this really interesting phenotype.. If I'm on a rotation and I get to know a resident kind of well and they hadn't heard about it, maybe I'll bring it up with them. And invariably, invariably, they're excited. They're like, whoa, this is cool. This is really, really cool. And then they'll tell the attending, we'll end up having like a little journal club about it. And I, as the medical student, the lowest person on the team, you know, in terms of the academic hierarchy, get to bring something to the table, something interesting I did. And we get to again discuss physiology. And what we can learn from it. So overall, I've just felt really proud to talk about this and discuss this with my peers and seniors who have all been really curious and really humble. Even when I'm in cardiology and lipid clinics, look, I sit there and I defer to my senior attending. I will shadow them, work with their patients, and see what their insights are, how they talk to patients, you know, coming from different walks of life with different conditions. And I have a ton to learn. But when the time is right and we have downtime, we might talk about the OREO versus statin study and all the literature around lean mass hyperresponders, and they are always, always excited to learn about it. And again, just to emphasize, this isn't just about one n=1 study. That is connected to things like our meta-analysis of randomized controlled trials, our interventional trials. We have a whole body of literature that's growing, and people who are truly genuinely at heart curious academics, they want to be on the forefront of discussing the science and discussing what needs to be done next, and also what's a responsible way to use the science at this point in time. Now, one thing that people ask about also is the, uh, clinical impact of the OREO versus statin study, which I think anybody with basic common sense could tell I wasn't trying to change clinical guidelines with an n 1. That would be ridiculous. I wasn't saying this is a study that should be generalized to anybody else and change their management. It was a provocative metabolic demonstration, a thought puzzle. I cast it as such, I caveated it as such. Nevertheless, there's another layer here, which was this was designed to attract attention to a body of literature, a body of literature which can inform choices in a responsible patient-physician relationship. So because of the OREO versus statin study, people have turned their heads. Have read about lean mass hyperresponders, the lipid energy model, and that has actually given physicians and patients—patients who are lean mass hyperresponders—tools to manipulate their LDL, their ApoB, if they choose to do so. So I've gotten contacted by clinicians and by patients saying, "Wow, Nick, this is incredible. Not only am I fascinated by it as someone who's just a curious person, but I have felt caught between a rock and a hard place. Either myself Or with my patients, because they're using a ketogenic diet for this medical condition. They might be statin intolerant, or they don't want to be on a statin or a PCSK9 inhibitor or ezetimibe for whatever reason. And we haven't known what to do. But we actually found we can titrate in some carbohydrates and attenuate their LDL response. Or maybe they're not using a ketogenic diet therapeutically, and you can just add back 100, 150 grams of carbs. And we are in a happy place now where maybe we're We're carb cycling with them. They're happy, they're living their best life, they don't have to be on a medication, and, you know, everything seems to be hunky-dory. And we wouldn't have been aware of this if it weren't for Oreo versus statin. Now, they're not generally using Oreos because that's not the point. I'm not advocating for Oreo use, but the principles that underlie the experiment are what can be leveraged. Get back a sweet potato, get back some fruit if you can in that clinical setting. And that often leaves patients and clinicians both kind of happy, especially if the patient doesn't want to be on a medication, but they're willing to play with carbohydrates. And I've talked in other videos and other podcasts about different ways you can leverage principles of the lipid energy model even beyond food quality and quantity, food timing, you know, exercise loads, weight changes, types of exercise. You can use these principles in the lipid energy model to manipulate LDL levels, which is incredibly cool. And yeah, it does have some clinical benefit if you're willing to experiment a little bit in a safe manner. So, if there's been any clinical impact, I would argue strongly that it's been positive. Now, as for those who are concerned that I'm fooling people into thinking Oreo cookies are a health food, I honestly have met zero people who have been hoodwinked into thinking Oreo cookies are healthy. Sure, there's definitely a lot of jokes about it, but I think if you stop and think about that criticism of this work, you probably come to the conclusion that any basically intelligent, common-sense adult knows Oreo cookies are not a health food. And if they're looking to eat Oreo cookies for health, they probably weren't gonna eat them anyway. Which brings me to, um, confirmation bias and the topic of social media. Now, There are some people making certain claims, um, using this Oreo versus statin. You'll see comments places, oh, this proves high LDL isn't dangerous. What I'd say is this group of people that probably have pre-existing confirmation bias, they're going to have this opinion anyway, and they might manipulate, leverage the story to just try to make a point that they wanted to make. But that didn't really sway anybody's opinion. At least I don't see it swaying anybody's opinion. Now, there are always pros and cons, or there always were gonna be pros and cons about doing this experiment. I was never exactly sure about how the balance of conversation would lean. I'm very happy, now thinking in retrospect, about how it ended up leaning, but that is dependent upon the fact that people really try, us as individuals, you as a listener, other academics, even my detractors, try to actually have a nuanced discussion. About what the purpose here was and what the implications here are. So sometimes people will come out and say, "This was bad because..." fill in the blank. And the fill-in-the-blanks are usually things like, "Nick is saying high LDL is good," or "statins are bad," or "statins are ineffective," or "Oreos are healthy." I've never said those things. I don't say those things in the paper. I clarify the purpose and the scope in the graphical abstract, in the video abstract, in the text itself, all over social media. I could not be more clear about this. And if any individual wants to try to manipulate the purpose, I mean, that's on them for sending a negative message, because those were never my points. It was always gonna be that people try to strawman or fabricate a strawman and put it out there so they can knock it down and get points for, you know, attacking the keto zealot, which is a little bit ironic since I was eating Oreo cookies and taking a statin. But anyway, that aside, people will always construct strawman arguments. They tend to do so in part, I think it's to rile up their base and get attention for them. There was always going to be, and I anticipated this, those who would want to take this, try to package it in a negative box, then attack that box to get attention for themselves. We see this again and again. If you want to see my reaction video, for example, to Lay Norton's coverage, You can see that where I go point by point, where people just, I think they're a little bit lazy in their interpretation. And maybe it's unintentional, maybe they're just ignorant and not willing to actually inform themselves about the study, the context of literature around it, and the physiology underneath it. Or maybe they're intentionally manipulating the narrative because it's juicy to say that this is being mobilized by people to do X, Y, and Z bad things. Negative attention is generally very good for clicks. So people have tried to leverage this against me, but what I would say is I stand by what I have been messaging. I as an individual, which is, this was a metabolic demonstration meant to provoke curiosity, and on balance, I think it's done that. And for those who want to just look at the surface level, read the headline and say, "Oh, he must be concluding," Oreo cookies are healthier, or he must be concluding something about LDL and putting a value statement on that, that's on them for either being intellectually lazy or just being uncomfortable with the cognitive dissonance that this study provokes. Because what I really did here was create a tension between two things, which is that Oreo cookies, selected because we can agree they're, quote, a bad intervention, right? Nobody's saying Oreo cookies are healthy, we're clear on that. This was a quote "bad intervention" which yielded a quote "good outcome"—LDL lowering. That's what it's, you know, presumed to be, a good outcome. And so how, how do you hold those things at the same time? Because they clearly seem to contrast. Bad intervention, good outcome. And I'm not here to resolve that for you. I'm here to put that to you and have you sit with that uncomfortable tension. The uncomfortable implicit questions that it brings to the fore because there's a paradox here, and that paradox means there's something we aren't understanding. And I want you to be aware of that uncomfortable tension and stay curious. Think, what don't we understand here, and what can we do next to figure it out? Because this is a curious finding, and a curious finding should provoke us to engage in the scientific process and to develop more answers. Science isn't about leaning away from uncomfortable observations, it's about leaning straight into them. In fact, charging at them. So that's what I'm encouraging you to do. That's what I want to do. Hope that makes sense. Now, about what's next. Well, always— I would never have done this if I had unlimited money and resources to do the studies I want to do. The fact of the matter is our resources are limited, and yes, that includes my money. And what I really want to do is mobilize the people and the tools I have— this could be through crowdfunding, it could be through philanthropy— to get resources to do the experiments that will actually have impacts on clinical care and true understandings of the science. This includes things like tracer studies, which are phenomenally expensive. We got a quote for a tracer study that we wanted to do with 30 people. It was $2 million. I don't have $2 million. If you have $2 million you want to give me, then I don't need to do Oreo versus statin. Give people a look and then maybe give us some money to do the experiments we want to do. Or another experiment I really want to do, which is an extension of Oreo versus statin, is a larger-scale randomized crossover trial where I compare carbohydrates to statins to ezetimibe in lean mass hyperresponders, pre-existing lean mass hyperresponders, maybe for 6 weeks each, with long washout periods between. And we see which is most effective, and what heterogeneity there is, and what's the source of that heterogeneity in lean mass hyperresponders. That, I think, will be a win-win-win for everybody. It gives patients and clinicians tools, and it advances the science. And I said the win-win-win, 3 wins, because I guess patient, clinicians, and scientists. So anyway, that's more or less where we are. Again, I am really, really heartened and excited by the reactions, and it's only been 3 months in. There is so, so much more to come. I mean, this really has been 2023, 2024, the year of the LMHR. Early on, we've had about 8 papers roll out. And to close, really, I just want to read some quotes because I've collected dozens, hundreds really, of quotes from people. Here are 2 that I want to highlight about OREO versus statin. The first one was from a cardiologist. This was me presenting at the Metabolic Health Summit where I presented the OREO versus statin trial. When I saw you present these data, I was sincerely stunned. Were William Cromwell not the senior author, William Cromwell being a highly esteemed lipidologist who served as consult and senior author on this paper, I would probably have been too skeptical to give the data a serious look, but I'm glad I did. Now that I have a better understanding of the literature base, I must commend you on what was a creative and utterly ingenious experiment. 'This singular work certainly sent me down a physiology rabbit hole, and I feel both excited and honored to be on the cutting edge of what I'm sure will be a revolution in our field. Keep up the good work, Nick.' That felt pretty good to read. Or another comment— this was not from a cardiologist, it was just a part of an email I got— 'I love how you blend rigor and fun, how you were transparent about your hypothesis and put yourself out there publicly, prepared to fail or fly, to depending on what the data showed. You've stimulated so many to think and learn, provided they're willing to. Your shine will attract attention. I only hope you don't sell out to Big Cookie. We need you. And don't worry, I won't sell out to Big Cookie, and Oreo hasn't approached me, and I'm definitely not doing another Oreo experiment anytime soon because that was unpleasant. So, uh, anyway, that's my 3-month update. Hope you found it interesting. I— I have no regrets about doing this experiment.