Dr Rupy: Does saturated fat cause heart disease?
Nick: Since we're doing rapid fire here, I'm going to say no. No, it does not. High level, saturated fat can change cholesterol levels, but the data showing that whole foods rich in saturated fat cause heart disease is rather weak. So I would not be afraid of saturated fat as a blanket statement.
Dr Rupy: If one is looking to reduce their risk of heart disease, should they try and maintain a low LDLC or ApoB cholesterol marker?
Nick: It's one variable among many that need to be taken into context. It's a variable to consider.
Dr Rupy: Can you live a long, healthy life on a high fat, high animal protein diet?
Nick: I think so, yes.
Dr Rupy: Will eating Oreo cookies lower my cholesterol?
Nick: I have to know more about your metabolic profile. For some people, it might work. I wouldn't say the majority, but I think that's one of the really interesting things about metabolic health, is that in each way, we're each outliers in some way, I should say. And figuring out what that is allows you to get pretty profound, let's say, metabolic results, like lowering your cholesterol with Oreo cookies, which is possible for some people. Actually, as an aside, I know this is supposed to be quick, but that was an experiment you're alluding to that I did. I've had, actually a doctor at Harvard text me the other day replicating it. Like people are doing it if they understand the physiology, it can be replicated. So, as an aside.
Dr Rupy: This is, this is super interesting. People are going to think that I've lost the plot.
Nick: People are really sceptical now, they're Googling off. Go to PubMed, type in Oreo versus statin, see the paper, then you're going to be like, oh, now I want to come back and have a little chat about physiology.
Dr Rupy: Look, Nick, I'm really, really glad that we connected. I've actually been following your work for a little while, and I think it's a, it's really important to shine a light on voices that are not necessarily being controversial for controversy's sake, but actually talking through different mechanisms, particularly within metabolism, that should be discussed at an academic level because the science is not settled on a lot of different things. So, before we go into this, I'd love to sort of dive into a bit of your story into how you even came into this sort of field of keto, carnivore diets. I know that's not necessarily your whole thing, but what is sort of like your origin story, so to speak?
Nick: So, I grew up in a medical household, always wanting to be a doctor, always wanting to be a scientist. Both my parents are physicians, and my dad's a scientist as well. And I grew up not thinking much about nutrition. I was aware of what healthy looked like from a conventional viewpoint. I knew to eat my five a day fruit and veg, to get enough protein, to get my micronutrients, which I thought it was fine to get them from say fortified cereals. And I was a young, athletic kid. So, beyond that, I didn't think much about it. I think I had a perspective on nutrition and metabolic health science, I didn't even know that term at the time, metabolic health, but that was very like, it's there, it's in the background, it's kind of a fluffy science. And I was, you know, got away with that approach, was pretty healthy through most of college. I was always pretty academic. I was an athlete, so I was a marathon runner, I did martial arts, calisthenic competitions. I have a couple state push-up records, at least for the under 18. But, during college and then at the end of college into grad school, I started to deal with different metabolic health issues. I don't need to go into the nitty gritty of each of them, but my bones started to weaken and I also developed ulcerative colitis, which is an inflammatory bowel disease. So, apologies for the graphic warning for people, but those who don't know, with ulcerative colitis, at least in my case, I was having bloody diarrhoea a dozen times a day plus. And you can imagine that is embarrassing, uncomfortable, very uncomfortable. It's not like a normal urgency. If there is blood in your intestines, that kind of irritation is next level. You can't hold it, I'll just be honest. And then there's the psychological torment on top of that. You can imagine being someone who perceived myself as very high achieving, athletically, academically, socially. I started to withdraw from a lot of that. Like, imagine trying to go into an exam. I wasn't even worried about picking the right answer on a test. I was worried like, am I going to have a flare mid-exam? You know, in college, you're a young guy, you kind of want to socialise romantically. You're not going to have a girl over if you're going to be like, you know, I have to take a break, I'm about to bleed out my ass for a minute. Kind of kills the mood. And opportunities that arose, like I'll never remember, I'll never forget the moment, sorry, I'll always remember, the moment that I had the opportunity to give the valedictory address at my college. I went to Dartmouth College. You can see it on the internet, and if you watch the video, it wasn't a very good speech, I'll be honest, but I was pretty composed. But I remember in that moment feeling the most terror I've ever felt because it was going to be in front of 11,000 people, recorded to infinity, and I was in the midst of a flare. So I'm like, am I going to have a flare, bloody diarrhoea, in front of 11,000 people, my peers, their family, YouTube, you don't want to go viral for that. And so, you know, internally, like I'm literally walking up to the stage, I'm like torn up, dying inside, but on the outside, I look composed because anybody that deals with these sort of things, there's a lot of people with invisible illnesses, you just learn to cope with it and to hide it in order to get through in life. But that's where I was. Then I finished up college, went to grad school at Oxford, and then things got their worst, and I ended up in and out of the hospital, ICU, palliative care, losing a ton of weight, like dangerously low weight. I was so malnourished, like my heart rate just started dropping into the 20s. And I really became quite desperate. So, at that point in time, I tried a lot of different things that were quote evidence-based. We can unpack what that means because I think it has a light and a dark side, the idea of evidence-based medicine. But nothing had worked for me thus far, so I started getting experimental. And after trying a bunch of different diets, I had no foot in one diet camp. I'd rifle through basically any diet you probably heard of, I probably tried. I tried a ketogenic diet. And for that, the response to that, it worked for me. It was undeniable that it worked. My symptoms improved, my inflammatory markers dropped, and eventually I got a colonoscopy and I was in biopsy-proven remission. It didn't evangelise me to that given approach, but it did peak my curiosity because it's like, okay, hold on. I've had this idea my entire life growing up that we need to go to the most rigorous evidence, right? The randomised control trials, and that's how we're going to determine what's smart for healthcare. And yet, that hadn't worked for me. Something that was unproven definitely did, very potently. And I started to think more complexly and systemically about how we have built the incentive structure of our current research ecosystem and how we practice Western medicine, which has, it does amazing things. Don't get me wrong. Like, some of the things we've innovated are truly incredible. And Western medicine has its place. Nevertheless, the business infrastructure we've built up around the food industry and the pharma industry has led to a dysfunctional set of incentive structures that I think puts what I consider metabolic health in the back seat to the detriment of a large population of people that suffered like me with some sort of chronic disease. And that's more or less what got me into this space.
Dr Rupy: There's a lot to unpack there. I really appreciate you sharing your story as well. I want to go through a few terms just to keep the listener and the viewer on track with everything. But just diving a little bit deeper into your IBD, were you on drugs at the time, like disease modifying drugs or steroids or anything like that to control flares?
Nick: First line therapy is something called mesalamine. It's not really important, but I was taking that. During flares, I'd take steroids, including steroid enemas, so you stick a steroid up your bum. That's more for the acute flare, but I had tried those and the flares kept coming back.
Dr Rupy: And the diets that you tried, so I'm assuming you tried like Mediterranean diet, high fibre diet, anti-inflammatory diet, maybe even an exclusion diet, like an elimination diet?
Nick: Yeah, the go-tos you'll hear for like IBD and IBS, like specific carbohydrate and low FODMAP, I did those. Mediterranean, paleo, pescatarian, vegetarian, vegan, whole 30, various forms of anti-inflammatory diets, which is kind of like a fluffy umbrella term. But yeah, I tried a lot of things before I tried a ketogenic diet, which I had my biases against just because of how it's talked about in the mainstream.
Dr Rupy: Yeah, so it sounds like, you know, to go all the way to keto, you would have gone through all the other diets before getting to that point because it is quite a an outlier, I don't want to say extreme, but I want to say an outlier diet in terms of the steps to get there. It's very, very different to a Mediterranean diet, and we'll get to exactly what we mean when we say ketogenic diet because I've heard you say there is no such thing as a ketogenic diet, there is ketosis and there are ways in which to get to ketosis. So, I want to unpack that a bit. But when you were going through these different diets, I'm assuming you were doing it in a rigorous scientific way, as a scientist yourself, looking at subjective markers of improvement, maybe not inflammation markers because otherwise you'd be going and getting your bloods done, you know, however long you're doing the diet for. But was that sort of the process you were going through when it came to your response?
Nick: I would say that I tried it rigorously in so far that I designed the diet in the best way possible that I thought would maximise the outcome. So, for example, if I do a vegetarian diet, it's not like I'm slamming Oreo cookies because they're vegetarian. I'll leave that for later. But, you know, it'll be like a whole foods vegetarian diet. I wasn't like getting like weekly markers and trying to analyse, you know, everything that was happening with biomarkers because quite honestly, I didn't care. I just wanted to feel better. So all that mattered to me, and I think people can empathise with this, is like, you're going to base what you do in terms of your lifestyle on how you feel. And sometimes, and we'll get into this, you can feel really great and then something can happen in your biomarkers that is, let's say, at odds with how you feel or perceived to be at odds with how you feel. So you try one thing and you feel amazing and then you look at your biomarkers like, hang on, what happened there? That's not good. Nevertheless, when you're coming from a place where I was, you know, you go with how you feel. Like, you know, if you say, oh, this biomarker might shed five years off my life, but I don't have to be sitting in the hospital, emaciated, brain fog, socially withdrawn, then you give up the five years. So, I was basing up basically on how I felt, but I did the diets and what I thought was a rigorous manner and certainly and importantly for a sufficient time to give it an effort. It's not like I tried three days and I'm like, it's not working, move on. Like I gave it several weeks, as one should, provided I didn't have very negative side effects.
Dr Rupy: Gotcha. Okay. And so, when you describe a ketogenic diet that you were on and perhaps still practice now, I'm no doubt it might have fluctuated in terms of the exact number of saturated or the amount of saturated fat and the amount of protein that you consume every single day. Where did you get your information from at the time? Because it would have been quite fringe. And how long ago was this, sorry? Just to give us some time context.
Nick: June 1st, 2019 was when I started a ketogenic diet.
Dr Rupy: Oh, wow. Okay, right. So about six years ago. So yeah, where were you getting the information around the ketogenic diet potentially being useful for IBD?
Nick: I did have one doctor. Ironically, she was the doctor that treated my dad for obesity. He went through her weight loss program. And he's like, my dad's like, you'd really get along with this doctor. Her name is Vivian Lowe. And I'm like, Dad, I'm trying to gain weight here. Like, she just helped you lose 50 pounds. I'm not going to do an obesity doctor. But she was someone who was pretty open-minded and versed in metabolic health and was the first person to, I can't believe I'm going to use this word, but I would say the first physician outside my family to give me permission to even entertain a ketogenic diet. I think at that time, you just hear so much about it negatively from conventionalists that it almost like, if you're kind of in that ecosystem, isn't something, at least in 2019, I entertained as like, this is a viable thing to do. Which sounds silly now to me, but I think her saying, look, this might work, what do you have to lose? And then mostly getting my information from her and from the internet. I mean, it's not that hard to design a diet that puts you into ketosis. It's like, all right, I get the principle, cut out the carbs, drop your liver glycogen stores, up the fats, go into ketosis. I can do that. So, yeah, I just kind of like, pardon the pun, but threw spaghetti at the wall with that approach. And lo and behold, my life took a hairpin turn.
Dr Rupy: I love that. I love that pun. You literally threw the spaghetti at the wall and never touched it again. So, in terms of the keto diet, can we, let's define that for folks if they haven't come across this before, because I think keto within the mainstream is just whip coffee, or whipping butter into your coffee and having a bunch of protein. But this is, I think it's poorly understood by folks. So when you say ketogenic diet or ketosis, what are we actually referring to?
Nick: So let's start with the idea of ketosis. So what is ketosis? Ketosis is a metabolic state where there are ketone bodies in your blood. Starting there, I think it's pretty obvious. It's named ketogenic diet because you go into ketosis. Ketosis is having ketones in your blood. Then we can ask, what are ketones? Well, ketone bodies are these really interesting molecules. The main circulating one is called beta-hydroxybutyrate. And, you know, one thing they do is fuel your brain. They fuel other organs too, but I focus on the brain because people might have heard that the brain consumes a lot of energy and it's kind of a picky eater. So it likes to run on glucose, at least when you're eating a mixed diet. Now, if you think evolutionarily, if we have these big brains and they like to run on sugar, and you know, we didn't always have access to food, what happens if you don't have food? If your brain needs sugar, where are you going to get the sugar? You're going to break down lean tissue. And if you do that, you know, evolving human ape, then you're going to break down your lean tissue quickly and starve to death in a matter of days and weeks. We need more robustness during evolution. So our body became much better at upregulating the system called ketosis where we turn our stored fat into fuel for the brain. So, you know, an analogy I've used before, not in a long time, but maybe it'll resonate with people if they aren't familiar with this concept is if you think of your brain as a fireplace and you want to keep the fire going, and you think of the fat molecules as like these long chains of carbons. So it's kind of like maybe a tree outside or a really long log. You can't take a full tree, bring it into the house and toss it in the fireplace. It doesn't work. You have to chop it up into little bits that can actually cross into the house, cross into the fireplace, in this case, cross into the blood brain barrier. And those are ketone bodies. So our body takes these long fats that we have stored, processes them into ketone bodies, and the ketone bodies can fuel the brain. So the brain isn't sucking up, you know, glucose in the form of, you know, processed lean tissue, processed protein. So that's one face of it. That's a way to think about like why are humans good at getting into ketosis, much better than other animals. It's because we have a big brain and we need to be able to fuel it even when we don't have carbs available, which we didn't always have. But that is not even the interesting thing. You can think of ketones as signalling, sorry, as as fuel, but they're also signalling molecules. So they're kind of like two-faced molecules. On the one hand, yes, they're firewood you can throw into the fireplace of the, you know, brain metabolism. On the other hand, they themselves are actually basically hormones. They secrete into the blood, they bind to receptors in cells and on cells and alter the ways our cells function at a very fundamental level. They can change gene expression. They can bind to proteins and change the function of those proteins. These are things called, sorry for the jargon, but post-translational modifications, basically putting a tag on another protein and then changing that protein's function, kind of like a dimmer switch or an on-off switch. So, ketosis becomes a very interesting metabolic state because it's not just you're running on a different fuel, it's like you are rewriting your body's metabolism. And every, almost every organ, if not every organ, is affected in a pretty fundamental and powerful way.
Dr Rupy: Gotcha. Okay. So, in because of evolution and because we have required the ability to withstand famine, let's say, during our long history, we would have had to have adapted a way in which we can utilise stored fat on our body as fuel. And that's one of the uses for ketones, but it's also, like you're saying, it's much more than just a fuel source. It's signalling, it's acting like a hormone. In terms of this transition from utilising ketone bodies by the brain, am I right in thinking that it's not a complete transition? So your liver is still going to be pumping out glucose as a result of gluconeogenesis. Your brain will still utilise glucose, but the proportion of glucose utilisation by your brain versus ketones goes more towards ketones in terms of the proportionality when you're in this ketotic state.
Nick: Exactly. So it's glucose sparing is what we would say. Think, you know, your brain can run on up to like 60 to 70% ketones, but not 100%. That is true.
Dr Rupy: Gotcha. Okay. And then in terms of the ketogenic diet then, how do you, how would you describe that in the context of what ketosis is? Because I imagine it's different for different people.
Nick: Yeah, so I mean, obviously you can, you know, based on what I just talked about, if you don't eat, you're not eating carbs and you're going to turn your body fat into ketones, that works to get into ketosis. So prolonged fasts, not very sustainable because, you know, very prolonged fasts are called starvation and you die, which is a negative side effect of any diet. But what you can do is just shift your dietary intake to have very little carbohydrate and fat. And then you're turning the dietary fat to ketone bodies. So, the ketogenic diet first became a medical intervention around 1921, I believe, for epilepsy. So treatment resistant epilepsy, doctors and researchers found that, oh, you know, you put kids with epilepsy on a ketogenic diet and their seizures tend to go away. That's interesting. So it's been a medical treatment for epilepsy for a long period of time. But, you know, like I said, ketones alter metabolism in many different ways. So in the, you know, past few years, decade or so, the use cases for a ketogenic diet and more broadly, I guess you could say therapeutic carbohydrate reduction, because you can get benefits out of reducing your carbs and the glycemic load of your diet, depending on your use case, even if you don't get into full-blown ketosis. But, you know, the use cases of ketogenic diet have expanded massively. So, it affects the brain, we know that. So now it's being explored for bipolar disorder, depression, anxiety, other mental health disorders and neurological diseases, Parkinson's disease, Alzheimer's disease, etc. Uh, there's even a case report on say ALS. So central nervous system disorders, autoimmune and inflammatory conditions, multiple sclerosis, I think there's a phase two trial on that. Um, and then insulin resistance disorders like obesity and diabetes are now all kind of within the umbrella of potential use cases for ketogenic diet therapy. As for what the diet is, as I described, it's just eating in a way that brings you to ketosis. That does require a very low carbohydrate diet. But beyond that, it makes no comment on the source of the proteins which you need and the fat in the diet. So, you can have, the way I like to think about it is it's like it's perpendicular to other diets. And what I mean by that is if you think about like there's a dimension on which you say this is the source of the food. So say like animal-based or from a particular region, like the Mediterranean region or plant-based, that's one axis. The other axis is what the macronutrient breakdown is. You can get your protein from tofu, you can get your protein from eggs. So you can design a ketogenic diet in lots of different ways. The fundamental piece is carbs low and sufficient protein and then fat high enough to get you into a sustainable state of ketosis, which you can measure in different ways, but the best way is just take a little meter and then prick your finger and get a little bit of blood and just do a capillary measurement, basically the blood measure of ketones is the most reliable way.
Dr Rupy: Is there a, I don't know, I haven't come across this technology, but in the same way we have continuous glucose monitors now, do you think there is technology out there that measures ketones over the course of a day?
Nick: There are continuous ketone monitors. I will say I've beta tested two. They're not very accurate. Maybe the technology has been updated. I tested them last, maybe about a year ago. So maybe it's been updated. I remember mine being relatively precise but not accurate. And what I mean by that is like, you could track if you go up and down, but if you cross reference the actual number to say a finger stick, they it wasn't really on the mark, at least for me. So the technology is there, you can access them. I just didn't find them particularly useful. But we are expanding the universe of continuous metabolite monitors beyond CGMs, continuous glucose monitors. So I would say, you know, in five years, we're going to have CLMs for lactate, CKMs for ketones, and hopefully a lot more.
Dr Rupy: Gotcha. Yeah, yeah. I look forward to that. And just to the avoidance of doubt for the listener, when we talk about ketosis, we're talking about nutritional ketosis here, rather than ketoacidosis, a state that you see within, you know, diabetics, for example, coming in as an emergency, which are very, very different reference ranges when it comes to measuring those ketones on on capillary measurements.
Nick: I think it's an important distinction for people because, you know, if you're a normal healthy person, say you don't have type one diabetes, you're not going to get into that dangerous place of ketoacidosis, probably. Because how it works is there's kind of like a feedback mechanism. So there's a lot of things called negative feedback loops in the body where the product of a pathway will inhibit its production. And this keeps things from just getting out of control and spinning out of control. But say you have type one diabetes, what that means is you're not producing insulin. Your body doesn't produce its own insulin. And insulin shuts down fat cells. It stops them from releasing fatty acids. So if you don't have that break on the fat cell, then the fat cell can keep spewing out fatty acids that get turned into ketones and you can get into a state where, yeah, ketone levels go super high. So, you know, a comparison of like nutritional ketosis like 0.5 millimoles to say, you know, say three millimoles is kind of like a normal range. Uh, you know, in diabetic ketoacidosis, your levels are at like 10, 11, 12 or more. So, yeah, it's a different magnitude of things. Like a healthy blood sugar, 90 milligrams per deciliter is different than having a blood sugar of 900.
Dr Rupy: We're going to go back to some of the potential use cases for nutritional ketosis because this is really, really interesting looking at all the potentials across different dimensions, particularly around brain health. Seems to be centered around brain health there, but but also inflammatory bowel disease. We've used the term metabolic health quite a bit. And I think that means different things to different people. So perhaps we should talk about what we mean by good metabolic, what what metabolic health means and how we measure the determinants of good metabolic health as well. And I think this also sparks an interesting conversation about what is a good biomarker.
Nick: That's a really important question. And I think one that often gets overlooked, so I'm glad you asked it. That said, I think we need to acknowledge that there are, there are terms we have when it comes to health that are, you know, kind of umbrella terms that people understand, you know, just viscerally, and then there's the ones that we can operationalise in science, which means like this term has like a concrete definition that can be measured. So I'll give you another example and then I'll answer your question, is ultra-processed foods. If I tell you avoid ultra-processed foods or your audience, they know what I mean, right? Don't eat Doritos, candy bars, right? But you have to ask the question like, well, why aren't we talking about them say in the dietary guidelines? Or, you know, why is it so hard to study these things? And it's because, well, how do you really define it? Like, how do you really, really define it? Because you need to know what are the biologically relevant changes that are happening to food. And just having this umbrella term of like, this thing is a processed food doesn't tell you how it's interacting with biology, so it's hard to define it and it's hard to study. It doesn't mean that it's a bad term. It just means, you know, the term has a different use. So it's like a heuristic. And I would say the same is true of metabolic health. People know it when they see it or they kind of get a sense of what it is, but it doesn't have a concrete definition in science. What I would say metabolic health is to me is that your body's machinery, you know, the subcellular, cellular and organ and system, sorry, you know I didn't get much sleep last night, and systems level, how your body is really running and operating is in a manner that minimises chronic disease risk and maximises function, physical function, mental function. So you're just running at your best. That's broadly how I think of metabolic health. And just as another kind of quippy thing, one person on an Instagram live once said, hey, Nick, in five words, how do you define metabolic health? And on the spot, my immediate response was your best life insurance policy. Something like that. So, you know, it's a fluffy term, but those are the ways I think about it. Now, you can get a sense or I would say, you can look at biomarkers to tell you if you aren't in good metabolic health, like they're canaries in the coal mine. So if you have a high insulin resistance score, very high fasting insulin, high triglycerides, which are a form of fat in the blood, you know, or low HDL cholesterol or low triglyceride to HDL ratio, a lot of inflammation, these are all markers of poor metabolic health. I say that with exceptions. For any given biomarker, there's an exception. So, are you in poor metabolic health if you're pregnant and your insulin's high? No. You know, if you just worked out and your inflammatory markers spike, that's not bad, that's a good thing. So there's always exceptions with this, but I would say in the general sense, having a healthy fasting insulin, healthy blood sugar, healthy levels of fat in the blood, low inflammation are all signs that you're more metabolically healthy.
Dr Rupy: Okay. So let's riff on that for a bit because I think generally most people would agree that if you're not insulin resistant, and we can measure that using some biomarkers, your triglycerides are low, your apolipoprotein B numbers are low, and we've talked about ApoB on the podcast before as a sort of umbrella marker for some of the atherogenic lipoproteins that are associated with cardiovascular disease. And some other markers that you mentioned or maybe even looking at visceral fat on a DEXA, etc, etc. But within this, and this will bring us on to the Oreo cookie study that might need a little bit of background into your particular phenotype, your physical characteristics on a low carb diet. Within that, you can have improvements in your biomarker whilst still actually engaging in unhealthy behaviours, as you went through in your N of one experiment. So this, this sort of brings up a bit of a conundrum because you can almost gamify some of these biomarkers to prove on paper that you are quote unquote metabolically healthy whilst still actually engaging in some unhealthy behaviours, as anyone would heuristically know, ergo eating Oreo cookies.
Nick: I love the way you said gamify. I think it's a really good way to describe it. And and and maybe speaking to, if I put on my medical student hat for a moment, and speak to this in a way that I think doctors will understand. If you ever take an endocrinology, endocrinology is hormone, you know, science for being a hormone doctor, if you're an endocrinologist. Endocrinology 101, what they'll tell you is if you get a lab report back, and everybody's probably seen their own lab reports, right? There are some things that are in the black, meaning they're in the normal range. And then you see the numbers that like pop out at you because they're red. And red means they're out of the reference range. And what an endocrinologist will tell you is ignore the colours. Because there's no such thing as a normal range. It's whether it's appropriate. So I'll give you an example, something called parathyroid hormone. A parathyroid hormone is released from your parathyroid glands, which are in your thyroid glands. One thing it does is it defends the calcium in your blood. You don't need, people don't need to understand the axis, the physiology, I'm just giving an example of how one hormone controls an outcome measure. Now, if this hormone is signalling to say get calcium out of the bones into your bloodstream, if your calcium is low, then where you want this hormone is high. That's what we would call appropriately high because then it's responding to a metabolic circumstance. By contrast, if your calcium in your blood is very high, you should get this report back and see the parathyroid hormone is actually red but low. That's appropriately low. And if it was in the black, if it was in the normal reference range, but your calcium was high, you'd say it's inappropriately normal. I might be losing people, the high level point here is a given biomarker needs to be taken in the broader context. So as much as I can say low insulin is good, or you might say generally low ApoB is better, you have to say, well, what is the context? And if something is off, why is it off? I think that's how you think like a scientist in the realm of health. So, with that said, the experiment that we've been teasing people about was one where I literally used Oreo cookies, adding them to my diet, not swapping anything out, I literally just added Oreo cookies in addition to my diet to lower a biomarker that people think is bad, which is LDL cholesterol or an associated biomarker is ApoB. In this case, just think about them as interchangeable. I have very high cholesterol. We can go into why that is. But the reason for my cholesterol, I actually do understand, at least I think I understand. And that understanding of the underlying physiology lets me make predictions and do pretty crazy things, including saying, hey, guess what? I'm going to do a party trick. And that party trick is, I'm going to do a study. Now, I'm saying this as in like, this is how it evolved. I actually announced publicly I was going to do this study before I did it. I said, I'm going to do a study. I'm going to for my high cholesterol take a lipid lowering medication. So a statin. In fact, a high dose statin, 20 milligrams of Crestor, it's like a gorilla statin. This is standard of care therapy for very, very high cholesterol. But I'm going to do it and compare it to something else. And what's called a crossover study. So a crossover study is when you do one intervention and then you do another intervention. So I am my own control. I'm comparing statin therapy to some other intervention with the outcome being my cholesterol levels. Let's see what lowers my cholesterol more. And the other intervention was, I keep eating what I'm eating. I kind of lock in a baseline diet, but I add Oreo cookies, 12 per day, which is one sleeve of Oreos, if you know your Oreo math, but 100 grams of carbs in just pure Oreo cookies. And I said, I'm going to do this experiment where I lock in my diet, I have a run-in period and I get my lipids, my cholesterol. Then I'm going to eat Oreo cookies. I ended up doing it for 16 days, measure what happens to my cholesterol. Then I'm going to do a washout to kind of reset. It's what you do in a crossover trial, at least the good ones. There are some bad ones where they don't. That's a whole another kettle of fish. Um, but I do a washout period for three months to reset and then I'm going to take six weeks of high dose statin. And I gave the statin six weeks because that's conventional for a statin. So I wanted to give the statin fair play, so I gave it more time than the Oreos. And I only gave the Oreos 16 days because I'll just put it this way. If you want to try at home, and don't actually try this, but if you were in theory to try locking in a diet and then eating a sleeve of Oreo cookies, 12 Oreo cookies in addition to your diet every single day, it becomes hard fast. It really does. Especially if you're used to being, you know, carb and sugar-free. So, it hit me like a train, I'll admit it, but the result was the Oreo cookies lowered my LDL cholesterol by 71% in 16 days. And the statin lowered it by 32.5%. So the Oreo cookies were two times as powerful as high intensity statin therapy, a trillion dollar drug market. It was two times as powerful, the Oreo cookies versus the statin in one third of the time. And it's a funny thing because on the one hand, you see the headlines, like you know I'm, I'm baiting the headlines trying, Harvard medical student or Harvard scientist lowers cholesterol with Oreo cookies. I mean, that was the, I'm completely transparent, that was, I was engineering this experiment to do that. And it did work. Like, I'm not coy about that. That is clearly, this is clearly clickbait. And you can call it that. But in this day and age, like, clickbait's a tool. I don't think clickbait's a bad thing per se, provided there's a purpose and there's nuance. And so you could say, yeah, this is a stunt. And I'm like, well, it's a stunt that I predicted based on physiology, then pulled off and published on with the support of my PCP, you know, the Harvard IRB exemption, I know how to dot my I's and cross my T's, and a very senior lipidologist on the paper. Like this is legitimate physiology. You can call it clickbait, but it's also real science that's pointing to something we don't understand. And so it was engineered to provoke emotions because what I have here is not a value judgment on LDL, not a value judgment on statins, not a value judgment on Oreos. But I know people think Oreos are unhealthy. I think we can generally agree on that. And I also know people think high cholesterol is bad. So, all I presented is a scenario where a human being, let's call it, let's say you're the doctor and a human being, a patient walks into your office, and you just notice this human being has done something very stupid that is a bad intervention, eating a bunch of Oreo cookies, but they had a good outcome or what you think is a good outcome, their cholesterol being lowered. And so you need to reconcile that. If there's a paradox, and this is a paradox, it means there is something we don't understand. So the experiment and others that I've done are engineered to be provocative, but to bring people in and say, hey, isn't this interesting? Now let's talk about what's going on. Not to judge an individual's lifestyle choice, but to say, this is an era where academia, Jade Tower academia, which used to be very siloed, is forced to interact with the general public. We as academicians are forced to talk to the general public. And if we don't step up to that responsibility, you know, rando influencers are going to, and they do. And then I know a lot of my colleagues get all pissy and it's like, well, this is beneath us, we don't want to engage. I'm like, you kind of have to. Like we have to find a way to engage in this engagement bait environment. And I'm figuring out how to do it. That was one example, and it does bring people to the table and get conversation started. So, I've been on my soapbox for a minute, pause for questions, reflections.
Dr Rupy: Yeah. So, um, there's so much to unpack there. I think for the avoidance of doubt, uh, what your experiment was trying to prove was nothing to do with the health effects of consuming Oreos and reducing ApoB. Uh, and that's not a suggestion to people to remove their statins in place of an ultra-processed cookie every single day. But, uh, what you did, and I think the important note, just to underscore, was that you called your shot before the study. So, you weren't just messing around and like, oh, I wonder what happens. You actually predicted using your model what would occur to your blood results. And we can go into why that is for your specific case. Um, but I want, I want folks to appreciate that at home that, you know, it's we're not saying that this is a replacement treatment for cholesterol lowering therapy. So, perhaps to add a bit more context to the N of one experiment, we could talk a bit about your prior diet. So what your what your diet was looking like before in terms of the amount of carbohydrates, fat, and protein you were consuming in general sort of macronutrient ratios, whether actually that pushed you out of ketosis, uh, nutritional ketosis using your your your blood markers. And, um, why this is specific to a particular phenotype that I believe either you or your colleagues have have coined in terms of the terminology of the lean mass hyper responder, which I'll be honest, I would have never have come across had it not been for your content online.
Nick: Yeah, I would love to get into all of that. Before I do, I just want to give a major hat tip to my colleagues in this space. Um, uh, my my chief colleagues are Dave Feldman, a software engineer, turned obsessive lipidologist, and a friend of mine, Adrian Sotomayor, a professor over in Mexico. They are truly like brothers to me. Science is fun. When you do it with people that feel like family, it is the greatest gift. So I'm really appreciative for them and all the work they've done with me on this research. Now, with that bromance posted, um, yeah, so we've been studying this very interesting thing that happens when some people go low carb, their LDL cholesterol, the so-called bad cholesterol, just skyrockets, it goes into space. Now, this is really important to study because we've alluded to the fact that ketogenic diets are becoming more mainstream and more useful clinically for a broad range of conditions. Literally people, doctors treating their patients with schizophrenia with a ketogenic diet. Like remarkable things. And yes, the data are still being developed, it's still early stages, but the potential for ketogenic therapy in medicine is incredible. If you could put it in a pill, it'd be the most, you know, lucrative pharmaceutical of all time. But you can't. That said, there's a boogeyman, there's a, uh, a speed bump, a very big speed bump, and that is the cholesterol boogeyman, where doctors are afraid and patients are afraid that if they go keto and are eating a lot of fat, their cholesterol will go up. And the way we think about it viscerally is like having very high cholesterol is like basically like equivalent to having poor heart health and having a heart attack. So, we need to understand one, why does this happen in some people? Mind you, it's a minority of people. Most people don't see their LDL and ApoB go up on ketogenic diets. We can actually explain why that is. Um, but some do. And we have to understand why it's going up in those people. Now, I think the most pertinent thing for your audience is to describe why some, like what would predict some people having an increase and some people not. And the interesting thing there is the main predictor is actually how lean you are. Leaner people, those that are insulin sensitive with lower BMIs, tend to be the ones to see increases. In fact, we have a meta-analysis, which is a group of, you know, studies of the studies of 41 human randomised trials, looking at the trials and saying what predicts an increase in LDL when people go low carb, and BMI is the predictor. In fact, having a normal BMI, a BMI under 25, is five times as potent a predictor as being in the top quartile of saturated fat intake.
Dr Rupy: So just to confirm, sorry for the listener, is this the BMI before they've embarked on a low carbohydrate or ketogenic diet?
Nick: The BMI at any given time. So we even see it where, for example, you know, what I'm building towards is the leaner you are, the higher your LDL tends to go. And if you have overweight or obesity, you tend not to see LDL increases. However, it's so dynamic. So I've seen patients who start at, you know, they're 300, 350 pounds, they go keto, and their LDL stays stable and even drops. But then they keep losing weight. And then they hit like a BMI of like 26, 25, and then their LDL just takes a hairpin turn and shoots through the roof. So it's a dynamic thing, and it's really interesting. But to, let's say, put someone's mind at ease, if you want to use a ketogenic diet or carb restriction for say diabetes, obesity, which is probably still the most common use case, if you're overweight or have obesity, or, you know, type two diabetes, you're unlikely to see your LDL go up by any substantial margin. Sometimes there's a transitional period when it blips up, but you're unlikely to be one of these people that has the LDL jump from 90 to 400. Which we do see, but we see it in the lean insulin sensitive people, like me. So when I went keto, I actually started a ketogenic diet. It was very low saturated fat, actually lots of fibre and greens, very little red meat, lots of fish. And my LDL still went from 90, 95-ish to like well over 300. And then up to over 500. So I wasn't guzzling butter or anything. I was eating a pretty low saturated fat diet and yet my LDL went through the roof. To give a very simple explanation of why we think this happens, it's when you're lean and insulin sensitive, your body is much better at releasing free fatty acids from your fat cells. And this kicks off a cycle. We call it the lipid energy model, basically where the fat needs to get repackaged into these shipping containers that contain cholesterol as well. And then they get trafficked around the body. So people, if they want the details, they can look up lipid energy model. We have a paper on it. But the high level idea is if you're lean and insulin sensitive, your liver starts spitting out these cholesterol and fat containing particles so that the fat can be trafficked back to your little depleted fat cells and your muscles to fuel the muscles. And the result of this is very high LDL along with high HDL and low triglycerides. So, the official definition of a phenotype that I have, called lean mass hyper responders, is having an LDL above 200, an HDL above 80, and a triglyceride below 70, all in milligrams per deciliter. That is the definition. If you pass those three markers, LDL above 200, HDL above 80, triglycerides below 70, definitionally you are a lean mass hyper responder.
Dr Rupy: Just for the UK folks, so because we use millimoles per litre here. So in terms of the conversion, I've just got a conversion chart in front of me. So we've got 200 milligrams per deciliter is the equivalent of around 5.2 of your LDLC. And then did you say 80 milligrams of HDL?
Nick: Yes.
Dr Rupy: So that's around 2.1 millimoles per litre. And then your triglycerides is slightly different in terms of the weight, so that will be
Nick: 0.8 I think.
Dr Rupy: 0.8, yes, 0.8, yeah. Lower than 0.8.
Nick: So I would say, yeah, for the millimoles, LDL above 5.2, HDL above 2.4, and triglycerides below 0.8.
Dr Rupy: Gotcha. Okay.
Nick: I think.
Dr Rupy: Gotcha. Thereabouts. Okay. I'll I'll add a conversion table to the to the show notes so people can check to see that. Okay.
Nick: We have all these graphs with the 280, 70, and it's just in my brain. We should definitely put parentheses with the millimole version. Yeah. I admit I didn't have that on top of my head. I'm like, it's divided by 38.7. Yeah. So, yeah, no, I'm I'm Oxford would be ashamed of me. I never learned my conversion.
Dr Rupy: All good.
Nick: So yes, that is the definition. And I just want to add, when I gave that definition, I didn't give a BMI criteria. And that's because there's actually no official BMI criteria. It's just that this triad is very rare in people with obesity. Maybe with the exception of people that are very low body fat but higher BMIs. So if you're like a Dominic D'Agostino type, people know who he is, like super muscular person but higher BMI because he's so muscular, like the Rock or something, then maybe. But for your average person, you know, with a BMI that is more or less commensurate with an average body fat at that BMI, then yeah, you typically have a BMI that's less than 25 if you're going to hit those markers.
Dr Rupy: Gotcha. Okay. So for people who have embarked on a low carb or ketogenic diet to improve their type two diabetes, what you're saying is generally, particularly if their BMI is is above, let's say 25, I know that's not, there's not a specific marker here, but you don't see this corresponding increase in LDL cholesterol, ApoB, and triglycerides. In fact, you often see either a stabilization or a reduction. And actually, colleagues of mine that utilise low carb in general practice as a very effective form of therapy, metabolic therapy, would say the same thing as well. But there is a particular phenotype which you ascribe to yourself where you see the opposite in a lot of these parameters. In fact, a very high LDLC. And am I right in thinking yours is like in sky high, like familial cholesterol hypercholesterolemia high?
Nick: Yeah, over 500.
Dr Rupy: Over 500?
Nick: Yes, over 500. So, um, and in millimoles, that is like around 13.
Dr Rupy: I don't even have that on my chart, that's so high. So
Nick: It's, most doctors have never seen a number that high. As in like, I have a PhD and I'm about to finish medical school, and if I go to the Harvard Medical School campus and tell a senior doctor, I have a patient with an LDL of 500, and I've done this, not saying it's me, they're like, nah, you must be mistaken. And then I show them the lab chart, again, my name redacted, they're like, this must be a lab error. It must be. Or they have a very, very rare genetic condition called familial hypercholesterolemia, the homozygous form, which is something like one in one million. That is a very severe condition, but is distinct from the phenotype I have. So just to draw that distinction, because people do confuse it. In fact, if you've heard people like Peter Attia and others who talk about this stuff, talk about, you know, lipid levels on low carb diets, they often bring up the example of familial hypercholesterolemia. That is a very different thing than what I have. Because in that case, you have a genetic dysfunction where basically you can't take up lipid particles. So your genetics have broken your lipid metabolism. You are born with sky high levels. I have, I eat a standard American diet or an Oreo cookie rich diet, my LDL is 80, 90, you know, totally normal. Again, milligrams per deciliter. But if I go low carb, it goes through the roof. And then I add back carbs, it comes back down. So, it is a metabolic response to carbohydrate restriction, probably an adaptive one. And when I say adaptive, I mean to meet daily demands, because you can have something that is momentarily adaptive but long-term harmful. It's called antagonistic pleiotropy or it's in the category of it, if people want to go down the rabbit hole on that. But that aside, what's really, really interesting about this population, and the reason everybody in medicine and health should care about it, not just lean mass hyper responders, is there are very few times in the natural world where like nature just hands us the perfect natural experiment to investigate a question that we wouldn't otherwise be able to do in a such a rigorous manner. So, what question am I talking about? Well, the lipid heart hypothesis. People talk about, you know, high LDL, high ApoB driving cardiovascular disease. And a question that's remained is, you know, is that high LDL alone just sufficient to be like, you mentioned the word atherogenic, you know, heart disease causing, forcing by just bulk flow. I think people imagine the particles containing cholesterol floating around the blood, they just like force their way into the blood vessel wall and then the plaque grows. And that's kind of the way we think about it. But there are a couple problems with the current literature. One, most people being studied are metabolically unhealthy because most of the population is metabolically unhealthy. So that's a different circumstance. Then two, the only other scenario where we have very high LDL and decent metabolic health at a population level is this familial hypercholesterolemia, but that's a different scenario because you have a broken lipid metabolism. So in studying people like me, we have the first population ever where we have isolated high LDL as a variable in a metabolically healthy context. And we can ask the question, well, one, why is this occurring mechanistically? But two, what's the risk profile? And I actually have a surprise for you. First, I have to ask, can we hold this podcast for a couple of weeks before release?
Dr Rupy: Okay. Yeah, we can do that.
Nick: That's because the trial that has been years in the making, the prospective trial where we are assessing these people like me, tracking them over time for heart disease progression, we found out two days ago that the paper was accepted. So it's about to be published.
Dr Rupy: Wow, okay. Congrats.
Nick: Uh, thanks. So this is big news. Uh, it's embargoed until the paper comes out, but provided we're not dropping this podcast until I give you the go ahead, I will talk about it. Um, before I do, I just really need to again, again, reinforce that this comes from the blood, sweat and tears of my friend, colleague, brother, Dave Feldman, who, you know, there are few people in science who have so much intellectual integrity to have risked their entire life's work on taking a pivot, doing something extreme. And what he has done and provoking this question is unprecedented. Having made an observation, put it out publicly, crowdfunded a clinical trial is nothing short of incredible. And just to put in another plug, it's become so big that there's actually a movie around this research that will be public probably around September. I have seen the first screening of the movie. We did it in February in Vegas before a conference and it is the first thing on on on the big screen that actually brought tears to my eyes. It's that good. It weaves the human elements with the science so beautifully. Um, so people should absolutely see it. It's called Cholesterol Code. You can look it up. There's a movie website. Anyway, that all aside, the trial that Dave got up and running was to take 100 people like me and measure one, is there plaque in their blood vessels after so much time on a ketogenic diet? That paper was published a little while ago. Uh, actually ended up being the number one most read paper in the journal of the American College of Cardiology Advances for 2024. Um, proud of our team for that. But, uh, then we followed them over a year with high resolution cardiac imaging, coronary CT angiography. And yeah, the paper was just accepted. And the results were that for the vast majority, there was no or minimal plaque progression. That this population did not appear to be a high risk population on the whole, um, despite having astronomical LDL levels. And more to the point, because you're always going to see progression in, you know, a large enough population, it just happens with aging and time. You know, being a lean mass hyper does not make you impervious to LDL. Ask the question, what predicted LDL, sorry, plaque advancement? What predicted over that time if you had plaque that grew? And LDL and ApoB did not predict progression. So across the spectrum of people, LDLs from 200 to 591, LDL just and ApoB did not predict. It just wasn't important in predicting whether or not plaque progressed. Which sounds heretical, but it's what the data showed. You can see the graphs when the paper comes out. What did predict whether or not LDL would, uh, sorry, plaque would progress, is baseline plaque. So if people have plaque at baseline, as measured in this case by a coronary artery calcium scan, it did predict more plaque progression. So the punchline is, in this population, plaque, having plaque begets more plaque. But LDL and ApoB do not. And that's a really important finding, um, because it doesn't say no, it doesn't say like ApoB and LDL aren't important. It says, or it reinforces, I should say, in the era where we have, you know, monitoring, you can just, you can go and get a functional test and measure the plaque in your heart. That is the best thing you can do. There is a lot of diversity, a lot of heterogeneity in how different people have plaque build up or not in response to having high LDL. So you can guess, you can speculate, but the best thing is to get a measurement of your own plaque levels. And if you have plaque already, it probably predicts more plaque progression and you should be more conservative. If you don't, and we can go through individual patient case examples, it's pretty reassuring even if you have high LDL. So, actually, I will just give you one example because I think examples, human examples are pertinent. That of my own mother. My mother, she's a physician, so, you know, she can, you know, make her own health decisions. But she's had high LDL her whole life. Her LDL in milligrams per deciliter, apologies for people needing to do the conversions again, but has been, you know, above 160 basically her whole life, generally above 200. And years ago, she went low carb and she's very small and lean. She's about 105, 110 pounds. I don't think she'd mind me saying that. Um, and she became a lean mass hyper responder. So her LDL has been in the 300s and 400s. So over the course of her life, on April 10th of this year, so in a couple months, she turns 60. Over the course of her life, she's had a lot of exposure to LDL. So, you might think with all that LDL exposure, she might have plaque. She ended up getting a coronary CT angiography and she had zero plaque. No measurable plaque. Despite having a huge exposure over her lifetime, for her, she decided, okay, I don't think I'm actually at that high a risk and the literature would support that. So she decided not to take lipid lowering therapy. She decided, I don't want to take a statin or a PCSK9 inhibitor or Zetia. I'm okay being not treated given I've had high exposure and I don't have plaque. If the results had turned out, oh, she actually has a lot of plaque, then she probably would have started a statin or other medication. So it's very individualised and I think, you know, this research is provocative because it says, well, one, just because you have super high LDL, even as high as say 600, it doesn't actually mean you're necessarily going to see plaque. Kind of like shocking. In fact, this is going to break some headlines. The total plaque score for six people actually regressed.
Dr Rupy: That's very interesting.
Nick: So despite having astronomical LDL, there was a regression of a total plaque score. And I think one had a non-calcified plaque volume regression as well. So, you know, again, that's not the majority of people, but the fact that it can even happen, really rubs up against modern cardiology dogma. So yeah, when this paper drops, hopefully this podcast can be part of us making some waves because you know I don't mind being provocative, provided there's legitimate things to be discussed. These are legitimate findings. They're not the end of the story.
Dr Rupy: Totally. Yeah.
Nick: But they, they force a conversation that's really difficult and that we need to have because people think, you mentioned the science is not settled. People think some of the science is settled. And it's so far from. And this is going to really reopen the books on I think some of the dogma and status quo thinking we have around lipidology. It doesn't mean ApoB doesn't matter and LDL doesn't matter for your average person. We reinforce that. It does mean context matters, nuance matters. And the reason I'm so passionate about communicating that importance is because what I said earlier is because in some way, shape or form, you, and when I say you, I mean the listener, you are an outlier in some metric. And coming to understand what makes you unique physiologically allows you to capture your health. I fundamentally believe that. I fundamentally believe the future of medicine is N equals one medicine, figuring out what's unique about you and then iterating based on that basic understanding to accomplish a health and a lifestyle that you could never imagine for yourself. I think that's the way forward. And so I think there's a broader truth wrapped around this research that that I want to communicate, which is why I'm so passionate about it. It's like a case study in physiological uniqueness.
Dr Rupy: Yeah, absolutely. And I think, look, when people get to listen to you outside of the short form tweets and stuff, I think they will recognise just how reasonable you are and how nuanced you are. And I think just to echo, you know, things that you've said, you're not suggesting that keto is for everyone. You're not suggesting that it is a magical formula for a long and healthy life. You're not even saying that it's good for your your gut. You're saying that for certain people, it can be therapeutic. It deserves extra study and a recognition as a way of, uh, putting conditions into remission, but also, uh, allowing for nuance within the risk profiles and characteristics of these individuals, particularly the lean mass hyper responders as an example. Um, and not to put words in your mouth, but I, you know, I, I feel that we lack that within the scientific discourse to actually appreciate people who are stepping outside the bounds of our guidelines when they are literally guidelines, not the rules.
Nick: Yeah. Yeah. No, I mean, medicine, whether or not I'm going to be a practicing clinician, I can appreciate what medicine is and it's an art. And it's an art of making hard choices with incomplete information. And the science will always be incomplete, which is actually what makes it exciting as a scientist. Um, people need to appreciate that. There's no one silver bullet that just because there might be a negative effect of an intervention that you like doesn't mean it's bad. It doesn't detract from your narrative. It just is. And the more we can be intellectually honest with that, I think that's a power, not a weakness. I truly do. Um, I think people see it as a weakness. Like, I, I talk, you know, in provocative manners about like, okay, you don't need fibre. Here's what we don't know about fibre, yada, yada, yada. At the same time, I'll say, I think on balance, most people, fibre is probably a decent thing. And I also express reservations about say going on a very long-term fibre-free diet. That doesn't detract from the amazing things carnivore diets have done for some people. I think it gives it power by saying, look, we can acknowledge the limitations of this thing. Nevertheless, it's having a tremendous impact. And I think by speaking with a softer voice, we can have a bigger impact. Sometimes. Um, and other times, it pays to be provocative. And I do want to, I know we're probably coming to time, but, um, I do want to discuss and invite your audience to give me true feedback and invite you to give me feedback right now on some of my conduct because I like to be transparent about my motivation. And sometimes I'll put something out in short form or long form or do something like my egg experiment or my Oreo versus statin where I know it's going to provoke emotions. I know everybody's not going to get it. I know that. I know it's clickbait, too. It's 100% clickbait. I'm not like pretending it's not. But my purpose is to stimulate conversations because like me or hate me, like the Oreo statin or not, like that worked at getting conversation started. Even if people were like, hey, Nick, why'd you do this? This sucks. And there's people got confused. I'm like, but now we're talking. And now I have five hours. It worked. Um, and more to the fact, actually, more to the point to give full transparency, like the knock-on effects of these sort of things are incredible. So, one, clinically, it got the word out there about research we're doing, including randomised control trials, meta of RCTs, to clinicians who weren't aware. Then they understood the physiology, then they started implementing the physiology in their clinic. So I've had doctors, including cardiologists, reach out to me and said, I had a lean mass hyper responder in my clinic. I didn't know what they were. I only became aware of it because of Oreo versus statin. They were statin intolerant. Now, I have lowered their ApoB by like 200 using sweet potato therapy. And I wouldn't have been aware of this if it weren't for Oreo versus statin. So, there's already having, I guess one could call positive clinical effects, but also people who understand the game, because to some extent, it is a game, are then willing to say, I like what this kind of spunky out there person is doing and now I want to fund the trial because guess what? I'm a 20-something PhD student, sorry, PhD scientist, medical student. I'm not getting millions of dollars from Big Pharma or from the NIH. So if I have a project that I want to do, how do I get it rolling? And there are philanthropists who are now backing projects. We have actually two in the works. One has a $2 million budget, one has a $3 million budget. And these are now achievable sums for me and my team to achieve off the back of things that are ridiculous as me eating a bunch of eggs. I know it sounds silly. I do. But if you can force a discussion, the currency of the modern realm in the creator economy is engagement and attention. And so if you can do something provocative, but then show up as the scientist who says, and here are the papers that I published on it, and I can have a long form nuanced discussion, then people are like, well, what could this person do if I gave them some actual resources? And so, I tell you this and I tell your audience this and I tell everybody this basically because it's like, I like being transparent, I like being authentic. Know why I'm doing what I'm doing because I'm going to keep doing it. Um, and the fact of the matter is, it works and I'm going to keep doing it until it stops working. Because there are important conversations we need to have and there's important research that needs to get done. The NIH, Big Pharma aren't giving me the money. I need to find another way to do it. And if I have to eat freaking Oreos or 720 eggs in a month to get it done, I will do it.
Dr Rupy: Nick, you're a, you're a fascinating, fascinating individual. And uh, this has been one of my favourite conversations, honestly. It's brilliant. Um, look, people should definitely go check out some of the experiments that you've done, like the, we didn't even get to it, but the 720 eggs experiment that you've got on your YouTube channel, uh, Cholesterol Code, I'm going to go check that out as well. It's out later on this year, you mentioned.
Nick: Uh, yeah, I think it's going to drop in like September or something. We haven't found out on what platform. The PR team's taking care of all of that. I mean, I, I, I can say this because I have no idea where it's going to end up. Like fingers crossed Netflix or Amazon Prime. I'm biased, obviously. I think it is, if it was on Netflix, I think it'd be the best nutrition documentary on Netflix that they've ever had. Yes, I'm biased, but it was so good at actually, one, being non-dogmatic, two, communicating science in an accessible, genuine way, three, showing that science is a process that everybody can engage in, and then four, and this was the real art, tying together so many incredible, touching human narratives. Like, there's this one story, I'm not going to get into the details, but like every single mother in the world will see that story and have their heart wrenched from their chest. Um, and then, you know, like young men will be touched by narratives of young men, older women, older men, like there is something in there for everyone that I think you'll just like understand the human element and be drawn into just how human science is.
Dr Rupy: Yeah, I love it. I love it. I'm, I'm very, very intrigued. Um, and you mentioned, uh, you've taken the decision not to be a practicing MD. What, what, what is, what is next on your trajectory in your career?
Nick: I can't give the exact details, but what I would say is, um, I found myself over the course of med school in a very unique place. I had a patient history, I had scientific training, I was training as a clinician in medical school, so I had like the medical perspective, the patient perspective, the scientific perspective, and fourth, I had the perspective of a young person coming up in a world that is complicated by social media and social media communication. And I was just thinking, what am I good at? Where can I have an impact in the world? What do I want to do? And I came to that point, you know, where I think a lot of us do at some point where we're like, there's so much I want to be. I want to be a scientist, I want to be a public communicator and a patient advocate. I want to be a good father and a husband. I want to be able to take care of myself, get some sleep, exercise. And you get to that point where you're like, oh crap, I actually can't do it all well. And I tried to think about like, what, what do I love? What do I get up for? And what I realised was what I get up for in the morning is getting people enthused about metabolic health and the science. Like, in my beginning of my final year or even in my third year, I'd be in my like internship, my sub-internships, sitting in the like intern room doing tasks for patients with my colleagues and be like, to be a fantastic superstar doctor, I need to be all here for my colleagues, on this medical sphere for my patients, and my brain just wasn't. It was like, oh, I saw the headline about this new nature paper. I need to read it. I just need to, I need to find a way to hear out a story to tell around it. That's where my heart was. And it was a big thing for me to come to the realisation that my heart, my calling wasn't in medicine. And it's because, not because I don't respect medicine and doctors, it's because I have so much respect for the profession. It is such an admirable profession. It's the one I grew up admiring to say in myself that this isn't my calling, that this isn't even my gift, one could say, was a hard admonition for me. I think there was some element of shame therein. To be like, I'm not worthy of it. But then I came to the realisation that like, look, what brings me joy is the science and communication. This is where I think I can have the biggest impact. And if that means stepping away from the career that I imagined myself for my entire life, and leaving it to other people, my incredible friends, um, you know, and people that are devoting themselves to this, uh, including I'm watching my girlfriend go through surgical intern residency right now. It's remarkable what she does. Like, I'm actually really proud to be like, they can do this better than I can. Um, I know what I'm good at. I know where I think I can have the biggest impact and I'm going to jump off the deep end and try to have that impact. Because, you know, this is, you know, a biomedical and scientific ecosystem. We all have our parts to play. I'm just finally figuring out what my part is. It was a really hard decision. It was the right decision for me. And I've also, I just want to express gratitude for all the people who supported me. I was really scared about telling my family, my mentors, one people might know Professor David Ludwig at Harvard. I was more scared about telling him than my own dad. I remember telling like, David, I'm not going to residency. And his immediate response was like, I've been watching you, Nick, like I know what you're passionate about. If this is what you put your thought into, like I trust you to make the right decision for you. So I've received a lot of support and, um, all I'm going to say is what people have seen from me thus far in my say rookie year in the public is nothing compared to what you're going to see after graduation. I'm devoting my life to this. I am so excited to grow and develop as a communicator and I have so much gratitude for my friends, my family, my mentors, and the people who take the freaking time to listen to me ramble for two hours about metabolic health or go on my YouTube channel and get excited about me talking about nature and cell metabolism papers. It's so cool that we have this community. Uh, I just, I'm, I'm grateful for the time and place I find myself in and for especially everybody listening because they make it worth it.
Dr Rupy: Yeah. Nick, all power to you, man. Uh, I see really, really big things. When you're putting all your energy into this, you know, if you're doing this whilst, uh, completing medical school, uh, like it's obvious that you're going to be an incredible communicator. And I want to, you know, support people like you who have this, um, what do you, what do you call it? Provocatively reasonable approach. Uh, and I, I, I love that. I love it. And, uh, we should definitely do a part two. I've got so many other questions around, um, topics around metabolic health. I'm sure our podcast listeners, uh, will as well. So I appreciate your time, dude.
Nick: Thank you so much. I really appreciated the conversation.
