Nick Norwitz studied why some lean, insulin-sensitive people get dangerously high LDL cholesterol on keto diets. He tested his own theory by eating Oreos for 16 days and dropping his LDL from 384 to 111 mg/dL, a bigger reduction than he got from statins.
The talk is "A Dramatic Metabolic Demonstration: Oreo vs. Statin." I'll repeat that. It's Oreo as in Oreo cookie versus statin as in statin therapy drug. Now, for context on this, we've been studying— we being me, Dave Feldman, Adrienne Sotomayor, a group of us— lean mass hyperresponders, which is a phenotype whereby when people go low-carb, they see their LDL go through the roof. Along with high HDL and low triglycerides. And this triad we call the lean mass hyper-responder. And we have a model to explain why this happens, along with a slew of papers around this phenomenon, including, you know, pretty rigorous research. We had a couple weeks ago a meta-analysis of randomized controlled trials published in the American Journal of Clinical Nutrition, which is a top-tier nutrition journal, confirming some of our prior findings that there's an inverse association between BMI and LDL change, i.e., it's the leaner people, in particular the lean insulin-sensitive people, they're the ones at risk for LDL increases on low-carb, which is a little bit paradoxical. Why would the healthy lean people be at risk for an increase in a bad marker when they go low-carb? In addition, we actually showed in this paper that being lean, just having a BMI under 25, was a much, much bigger risk factor, if you want to call it a risk factor, for LDL increases cholesterol increases when you go low-carb as opposed to saturated fat. So there's something in our current models that isn't quite clicking. However, it's been really, really hard to start this conversation. Um, maybe I'm just impatient and it requires time for the field to mature, but I want more resources devoted to this because I think it's incredibly important. I think LDL cholesterol is effectively the boogeyman of low-carb. It's what deters a lot of people from implementing it. So understanding the heterogeneity of LDL responses when people go low-carb, I think, and how to treat it if that's an objective for certain patients is incredibly important in order to increase the overall clinical utility. As we see ketogenic diets expanding for things like kidney disease and mental health disorders, we need to address this boogeyman. Why is it happening? How do we treat it? So like I said, we have a model. We actually have quite a lot of data, but people aren't talking about it. So I engineered an experiment that I thought would force everybody to look. I wanted to force the discussion. So I thought, "Okay, based on our lipid energy model, what is the boldest way I can test it with the most flair that is legitimate but will capture headlines so people will talk about this?" Now, according to our model, LDL goes up in lean insulin-sensitive people when carb stores in the liver go down. So, pretty simple, you add back carbs and the LDL response should be attenuated. LDL should come down in those lean mass hyperresponders. And we've actually shown this in multiple studies previously. We had a case report or case series of 5 patients, all of whom saw LDL decreases with reintroduction of carbs, things like sweet potatoes and fruit, so the healthy carbs, quote. Largest drop in that trial was 480 mg/dL in LDL. So massive drops, crazy, things you don't see with drugs. And then we had an interventional trial with 10 patients. Again, they saw the same response, but people weren't talking about it, presumably because it's not headline-catching enough. But again, according to the model, it just should be adding back carbs works. So I should be able to use any carb. Oreo cookies should work. I chose Oreos because it was, I think, the best branded unhealthy food that I could imagine. If you want to pause and ask yourself the question, can you think of another food that is universally recognized and universally recognized as unhealthy that's better known than Oreo cookies? I can't come up with anything off the bat. So that's why I chose Oreos. And then I said, I want a comparator. What's the obvious comparator? High-intensity statin therapy. So I wanted to compare these head-to-head in myself. There's an added flair there given that I'm like a Harvard medical student, so I knew that would be also a brand that the headlines could grab onto if they want to, and I'll let them do that. So I actually announced the experiment a priori on a vegan YouTuber's channel, Plant Chompers, who was willing to have me and Dave on. I announced it a priori because that's what I like to do. People can come along on the journey. This is my hypothesis. This is the protocol that I'm going to do, but I haven't done it yet. And we'll see what the data show. The data will show what they show. I also got my PCP ordering all the labs, so everything went straight to her, and a consultant lipidologist on board, William Cromwell, so an expert in the field, to add some extra legitimacy. And then I executed. And the punchline is it actually worked. It worked really, really well. The Oreos dropped my LDL cholesterol by 71% in 16 days. The drop was from 384 to 111 milligrams per deciliter. More potent than any drug. And then when I did the washout and compared to the statin, the most potent effect of the statin, the nadir, was a 32.5% drop. So the punchline is, in a lean mass hyper-responder on a ketogenic diet, Oreo cookie supplementation lowers LDL twice as much as high-intensity statin therapy. Which you read that, and it's been coming out in headlines, and it's like, 'Is this a joke? What's going on here? Are you trolling us?' And no, this is actually, like, legitimately what happened. And it was predicted by the model. It's consistent with other literature, and it's supposed to be shocking. It's supposed to be shock and awe and draw people in that haven't heard about this so that they can engage with the ideas, because it is truly remarkable. What we're studying really is everyday shock and awe to me, and I wanted to find a way to translate that into something that everybody could look at and go, "Whoa," and then become interested in our topic and hopefully, you know, acquire therefore resources, collaboration via attention and a kind of a grassroots up enthusiasm for the study of lean mass hyperresponders, lipid energy model, and what causes LDL to change on low-carb diets. So, the talk is "Oreo versus Statin," and hopefully people like it.
