SPECIAL EPISODE- Dr. Nick Norwitz Interviews Dr. Adrian Soto-Moto on Boundless Body Radio!

Hello and welcome to Boundless Body Radio. I'm your host, Casey Ruff, and today is our third episode of this special format, and I'm super stoked to introduce our guest. Dr. Nick Norwitz is a returning guest and host of this special episode. Dr. Norwitz completed his PhD from the University of Oxford in neurometabolism and is starting his medical training at Harvard Medical School. He has an incredible and fascinating health story about osteoporosis, the Boston Marathon, ulcerative colitis, and more, which you can check out in episode 100 of our show. Dr. Nick Norwitz, welcome back to Boundless Body Radio.

Thank you, Casey. Really excited to be here and with our guest who I guess you're going to introduce now. Yes, we absolutely are.

Dr. Adrián Sotomayor is a specialist in internal medicine. Currently, he works as a clinical scientist and internal medicine consultant at the National Institute of Medical Sciences and Nutrition of Mexico. His line of research focuses on the human metabolism of ketone bodies and ketosis. Many diseases are characterized or worsened by fuel management impairments, and he is particularly interested in the potential benefits of his research and in patients with type 2 diabetes. Dr. Sotomayor, it's an honor to welcome you to Boundless Body Radio.

Thanks for having me, guys. I'm really thrilled to be here, and I am one of those people who are way harder to stop from talking than to inviting to talk. So if I— if at any point you want me to shut up, just say.

You're in the right place. We invited you so you could talk. As much as possible. We invited Nick so that he could be the host and interview you, so I'm going to turn the time over to him.

Yeah, um, so before we get started, I'm gonna, uh, do my, my obligatory job and embarrass Adrian a little bit, um, because I, I want, I want people listening to understand who you are to me because it's been a fun year. I've been on lots of podcasts, talked to lots of people. We've never been on a podcast together, and so You know, Adrian is a guy who spends a lot of time treating patients in the lab and doesn't have a huge public profile or persona, um, and so I think people need to know who you are. Uh, okay, first of all, he's a brilliant researcher and physician, but I'm not even going to go there. I met Adrian under pretty funny circumstances, which was, um, when I matriculated to Oxford. So I had just finished undergrad, straight out of college, I had never lived outside New England and end up, end up in Oxford. And, you know, it's a new world for me. I don't really have any connections. And, um, there's this guy in the lab one year above me. So Adrian was doing his PhD, um, at Oxford with me, and he was a year above me. But he wasn't just like one year above me, my peer. He was a lot more, uh, sage, I guess. I don't really have anything scripted. And advanced in terms of like, he had already done his medical training and residency in Mexico and had been treating patients then this hospital had, you know, given him resources to come do a PhD so he could do his own research. So I was doing my PhD straight out of college and then going on to do medical school. He had already done that. So it was really interesting for me to have someone who I could kind of consider a peer but who also had all this interesting life experience and expertise in an area I wanted to go into. Plus, he was always just super willing to like train me and teach me medical stuff. Like when I had to learn cannulations and we go into the lab, he's like, yeah, just stick me in the arm. And then I'd be screwing up and he'd be like adjusting. He's like, no, no, let me show you. And he's like adjusting it in his arm, things that would make people queasy. He was always up for getting like biopsied or X, Y, and Z, which was really fun. But I think I, I will always have a debt to him, and, and as will my parents, because as we talked about in episode 100 of the Boundless Body Radio podcast, you know, my story— I, I moved to Oxford And immediately started getting sick and ended up in the hospital. So it was like a couple weeks in and I keep on finding myself in the hospital and the docs there is like, who's your emergency contact? And I'm like, well, there's this kind of nice guy in the lab. And I call Adrian, I was like, would you mind being my emergency contact? And I can't imagine what was going through your head at that time. Like who is this nuisance child from New England creating havoc? But you're always so gracious and brought me my stuff and were always willing to like help me out. So From that day on, throughout our time together in the lab or just nerding out, you know, over our weekly Wednesday dinners at, uh, Iksun Sushi— and I am pretty convinced that the waiter and waitresses there all thought we were, we were gay. Nothing wrong with that, but we always shared the same two things. It was the, was it the jungle fish salad and the, the hamachi kama?

We share those.

So cute.

It was, it was, uh, I mean, we met under weird circumstances, but it was, uh, the beginning of a very, very nice friendship. And, um, we, we, despite being at different points in our training, I mean, I kind of did it backwards to the way Nick is doing it now. Um, we have lots of things in common, lots of interests. Nerd interests and of course keto metabolism. So, um, it was, it was, uh, perhaps not the standard way of starting a friendship, but it definitely became one of the most valued and fruitful friendships. Well, friendship relationships I've had.

No, I, I think we'll be connected for life at the hip. Um, even though it was really only a couple of years because it was curtailed.

Yeah, it's true.

But, um, sure. Yeah, it is. It was every science thing to every nerd thing, like Game of Thrones we watched together, MCU, movies, Infinity War. Have you seen Loki Episode 1?

Yeah, I already— I watched it yesterday. I was trying to avoid spoilers. All right, well, yeah, it's a strong start. But yeah, I mean, I think that my relationship with Nick is one of those friendships where you like— every conversation can be started just like at any moment. Like, you didn't actually need to say, hey, how you been? What's up? How's the family? You can just simply send a random meme you think the other person will find funny, and then don't talk for the next 2 weeks, but then send another random meme, or have you seen this paper? And it's, it's, I mean, it's a nice, it's a nice relationship.

Well, I actually don't think we've really talked since last March when like we left, or at least I left. Um, hey, and now we're just jumping on a podcast and we have no agenda whatsoever for We have no plans to talk. I think if we just have good chemistry, things will roll out. So I mean, I guess I'm interviewing. I do have some questions and we can dig into it and then bromance later. But since we have a somewhat limited time, I guess where I want to start, you know, a lot of podcasts we talk about like standard American diet and it's very American or UK-centric, but you're a practicing physician in Mexico, in Mexico City. So I wanted to talk a little bit about the unique challenges you face, things you see. If I'm correct, I think Mexico now has— it has the highest average BMI of any country in the world, except for maybe the UAE.

We have the fattest kids in the world.

So I, I want to first open it up for you to talk about what it's like being a physician studying what you study in Mexico, um, and you can take that wherever you want.

It's, it's, um, I would start with an anecdote. A few years ago, that this was perhaps 6 or 5 years ago, I'm, I mean, I'm embarrassed to have forgotten his name, but a professor from Washington U, from the metabolic lab at Washington U, came to the hospital I am working as a consultant now And this was his first time in Mexico. This guy specialized in obesity research, and he came, well, in a seminar or series of seminars about obesity. He started his lecture by saying that the night before, he met for the first time churros. Churros is a Mexican dessert. Made with vegetable oil, a ton of sugar, and the cheapest flour you can find. And he started his lecture by saying, you know, guys, forget about it, you're doomed. Stop doing obesity research, you're doomed, because there is no way that food is so cheap and so delicious to win this battle. I mean, when you face something as delicious as churros, as cheap as churros, and as harmful as churros, you're basically doomed. I mean, he described this as almost like an eureka moment when he tastes this perfect mixture of— and actually, they also have a little bit of salt— sugar, flour, cheap oil and salt, and amazed about, well, what he paid for it, for that dessert. And he said, I mean, we wouldn't win this. I mean, it's very hard for many different reasons, and I am convinced that people most of the time do not choose to be obese. And do not choose to become diabetic or to start living with diabetes. Most times it's a consequence of their circumstances. These circumstances are economic, are cultural, are perhaps emotional, perhaps have to do with many other non-metabolic factors. And Mexico is on the— I mean, needs to climb a lot of obstacles to solve those issues. Because first of all, it's way cheaper to buy Coca-Cola than bottled water. I mean, you could start by asking why we need bottled water, because not every part in Mexico has potable water. So some of them need bottled. Most people will prefer to buy Coca-Cola over milk. I mean, the milk debate is a different one, but it's way cheaper to eat white bread. And well, in Mexico we have something, in Spanish it's called pan dulce, which is like dessert bread. I mean, bread, as if bread on its own is not enough simple carbohydrate, we coat white bread with many different forms of sugar. And this is standard dinner for most Mexicans because it's cheap, because it's tasty, because it reminds you what you had when you were a kid. You also have some form of regional tribalism about the dessert in your town. I mean, it's a very complex phenomenon. It's not simply, uh, sugar is tasty. It's not only, uh, these, these foods are cheap. It's the mixture of culture with, with a— I will stress the, the, the regional tribalism about it because I, I typically say that Mexico could easily be 5 different countries under the same flag. It's huge. The whole UK, islands included, fits in one of our counties. Just, I mean, Chihuahua is larger than the whole UK, islands included. And you can find places in Mexico with many, many different climates, diets, patterns of work. We actually are the most— the genetically most diverse population in the world. There is this Science magazine paper, 2015. The same genetic distance you find between Southern and Northern Mexicans is the same distance you will find between Koreans and French people.

Wow.

So it's just too complex. We are genetically diverse. We are— there is a lot of inequality in Mexico. I mean, there's a lot of people who can afford very high-quality foods and a lot of people who can't afford high-quality foods. There are many different regions and therefore many different tribalisms about foods and desserts. And we are amazing in the kitchen. I mean, Mexican food is world heritage. I mean, we, objectively speaking, of course I'm biased here, but objectively speaking, we reached the level of witchcraft and sorcery when we are inside a kitchen.

That has been socially verified. That is socially verified. That is objective. You guys have the best food. No question.

It's a scientific fact. It's a scientific fact. And There is no way that if we are this good, food is this cheap, but it is also this bad quality, we are in the problems we are. We are the world's highest per capita consumers of soda in the world. We have the fattest kids in the world. Diabetes incidence is not even stabilized. It hasn't stopped raising for the last two decades. We are an aging population who will inevitably face the health and economic burden of losing lots and lots of working years because a good amount of their population simply cannot work because of the consequences of obesity, hypertension, and diabetes. So it is— I'm not going to say impossible, but it is definitely challenging trying to convince a patient in Mexico that the way they've been eating for their whole lives is causing most of their health problems. And it's challenging to find options they will find as appealing as what they would find in a family reunion every weekend. Yeah, it's, it's a different, it's a different challenge.

There's so much to unpack there. And I want to dig a little bit into those other factors you were referring to before we move on to the metabolic, because I know we'll get there, including the social factors, the economic factors, and then education. But starting with the social, because I find that such an interesting thing, starting with the principle that I think most of us three would probably agree that either sugar is an addictive substance or it's a substance of abuse. It's on that spectrum. We can hash out definitions later, but for the sake of argument, let's call it a somewhat addictive substance. If that's the case, it's unique in that most other addictive substances have a social stigma associated with their use, whereas with something like sugar or simple carbohydrates, there's a social stigma associated with their abstinence. So if you're someone who wants to go low carb in Mexico, just because of the social structure in the community around food that you are raised in and immersed in, I can imagine it'd be very, very difficult. I don't know if you can—

having to be fearful of offending lots of people. I mean, you would be, because it is, it is also a sign of appreciation to give sweets to someone else.

Yeah.

So rejecting those very frequent or usual gifts or not asking for a second round in your plate will make people think you don't like them or you didn't like the food they offered you. Or, I mean, it's, it's cultural. It's also very, very, very cultural.

So if I'm going to ask you a hypothetical, let's say you have a patient or just any person who wants to adopt a ketogenic diet, they know it's good for them, they actually are incredibly well-educated. Do you think there's a large proportion of people who, even having all that knowledge about kind of what they want to do, would accept that they're not going to do it specifically because they just— they're more concerned about offending other people in the social construct? They're like, I'll accept being unhealthy, or I'll accept being overweight, so that I can just function socially in this environment and not rock the boat?

It's definitely possible. I've definitely met patients as the hypothetical, not so hypothetical case you're describing. In Mexico, we have something called the Guadalupe Reyes Marathon. Which stands for the festivity of Virgen de Guadalupe, which falls on December 12th, to the Wise Men festivity, which falls on January 6th. So between December 12th and January 6th, every year Mexicans gain on average 5 kilograms.

On average?

It's, it's, it's— I typically, I typically measure these in babies. It's like you have 2 more babies, you know, like that's—

yeah, that's 11 pounds.

And it's, it's, it's— yeah, it's between 10 and 11 pounds. And this is standard, and because this is the season where people, uh, see their distant relatives and they have, uh, well, Posadas is literally, uh, party every single night for 10 nights before Christmas. So before you have this very, very large dinner on Christmas Eve, you have had a very, very large dinner for the last 10 consecutive nights. And in towns, in Mexican towns, people are used to a family hosts one of these parties every night. So there's also like a little competition on who was the best host, who offered more food. I mean, it's a vicious cycle. And I've had very well-educated patients who acknowledge they should go into carbohydrate restriction, but then say, "Can we do this after Guadalupe Reyes? Can we start this after January? Because I'm gonna meet with lots of people. I'm gonna meet my relatives. I'm gonna see my mother, or my mother is cooking." this particular dish for this, for our posada, and I don't want to offend anyone. So can I, can I start this in January? And of course my answer is, I mean, you can start this whenever you want, but I mean, bear in mind that if you start this in January, it's likely that you are starting 5 kilograms above what you are today. So it's, I mean, if I were you, I mean, I can't advise you to wait till January or to February to start this these lifestyle changes. I understand why you want to do them. Losing extra 5 kilograms, extra 11 pounds, it's not a trivial task. I mean, don't do things harder for yourself. It definitely happens. I mean, this cultural— I don't want to call them obstacles, but this heritage definitely makes things more difficult for even very well-educated and highly resourceful resourceful people.

Um, and let's talk a little bit about that, that education. Like, do you— I don't know, how do you think it compares to the United States or anywhere else in the world? Do you think people have access to education? Do you think there are public efforts to really teach people about nutrition?

Um, well, I mean, it's a funny, uh, thing you ask because actually almost Immediately after I returned to Mexico, I got invited by Mexico's Education Ministry to collaborate with them in an online course about nutrition. So this was— I used to complain that it was way more important for Mexicans to learn about nutrition than to learn, I don't know, the history, the very last detail of the history of Mexico. I mean, I don't care if you don't know the differences between the Constitution, the second and the third Constitution of Mexico, but I do care that you know the difference between trans fats and PUFA, you know, like this would be more useful. And when they invited me, My first reaction was, gosh, this is going to be lots and lots of work. Because what I replied was, I am only interested if I can put my insight into the scripts. I don't want to be just someone who records videos because, I mean, you can hire whoever for that. If I am going to do this, I want you to give me access to the actual scripts. At first they didn't like very much the idea, but after a while they accepted it, and I ended up recording 16 half-hour videos for this online, aimed to high school students, health and nutrition related course. And my experience after that, we actually finished recording those episodes like 2 weeks ago. Is that— it's definitely worth it. I mean, as happens with most projects, when you analyze them in retrospective, you are not 100% happy with the final result. I mean, I actually don't like to see the first episodes because I can't stop watching the things I would have done different. But, uh, well, Michael Crichton says, uh, that good texts are not written, they are rewritten. And I think that's the same for any educational product. And if these guys give me the opportunity to do it again, I would do it again. And if they give me the opportunity to do it 1,000 times, I would do it 1,000 times. Because when you compare the reach you have in one of these new and forcefully adopted online resources for educating people, the reach you have there is way, way larger than the reach I have in my private practice. Perhaps I can do things with more detail when I am one-on-one, but to, to go back to the original question, education is improving, is profiting from these COVID imposed new ways of teaching, and I am hopeful. And there is definitely a long path to, to, to walk, but it is improving. It was absolutely absent, and now at least is in the mind of decision makers and education content producers. So I hope this particular factor will be improved in the short or midterm.

That's a fantastic project. What were some of the principles that you taught high school level students in those 16 half-hour videos?

It was a very, very— it was a continuous battle, particularly when talking about traditional dishes. Because for example, there was, there was this episode about drinks, things you can drink, and refined carbohydrate— the worst kind of refined carbohydrates are of course liquid carbohydrates because they reach very, very rapidly your gut and they are absorbed almost immediately.

It's—

they have a higher glycemic index than their sugar content equivalent in solid food. Every region in Mexico has their traditional drink, which is a variation of corn flour plus sugar, or wheat flour plus cocoa and sugar, or a different process or kind of corn flour plus sugar, or you get the idea. So, I mean, none of these traditional drinks is actually a good idea. And they weren't so problematic until recently because they weren't drinks you were able to drink throughout the whole year. I mean, they were seasonal drinks and they were expensive to produce. And perhaps you had one or two of these drinks every once in a while. But now people can produce them every day and drink them every day. And they are perhaps marginally— I don't want to say better— marginally less worse than having a Coca-Cola. But because they are not a Coca-Cola, they don't inflict this guilt on people who consume them. And people think that because they are traditional and they are produced with natural ingredients and they are proud of their heritage, they think, oh, at least I'm not drinking Coca-Cola. I am having lots and lots of atole. Every day. Well, it's actually not that far. So that particular episode, for example, was very problematic because there is really no— there are no arguments to properly defend the health attributes of these drinks. And understandably, from the institutional point of view of the Education Ministry, they weren't— I mean, they didn't want to bash these drinks too badly because there's heritage attached to them, etc., etc. In the end, we didn't say never drink these things, but we also— I mean, but I made sure that, okay, these are very, very occasional drinks. Don't do them with just sugar. You want to be sure that if you are having sugar, have protein with it. There was— I managed to, to produce and to convince them to have an intermittent intermittent fasting episode. So this was— I am very proud of that. There was a tax-funded and publicly available, uh, with federal money produced episode about intermittent fasting, which, which I think it was very, very necessary. Uh, we did discuss how— I mean, for example, some people in Mexico believe that corn flour is less harmful than wheat flour, or some people believe that cane sugar is less harmful than sugar, although they are the same. And I mean, these misconceptions, uh, I mean, I wanted to be sure to make sure that these misconceptions, common misconceptions, were addressed in this episode. So I did as much as I could and the best I could to talk about, for example, we did another, another, uh, we managed to put a circadian rhythm episode inside the nutrition block, like trying to convince people that nutrition actually starts in the sun. So it's, it's, uh, again, it's not perhaps the complete or final result I would have liked, but it was close to it.. And I really would do it a thousand times because I believe I— it's likely I would have more impact with these videos than in my private practice.

Yeah, that's so cool. I'm so happy you were doing that, that project. That's awesome. Especially the intermittent fasting episode. Um, just because of— I want to get into other topics. I'm not going to go into the economics question, but let's shed a little hope. I mean, do you agree with the professor from the University of Washington who came in and said, bros, you're doomed? Or do you, based on your clinical experience, think that there is some hope? Do you have success stories of patients who have been able to pull off like a low-carb diet in Mexico? And, and how do they do it? What does a low-carb Mexican diet look like?

I mean, the short answer is yes, I have hope. The long answer is there is this phrase or quote from Mexico's wealthiest man and most successful entrepreneur, Carlos Slim. He says that the perfect recipe for mediocrity is pessimism. You can't— I mean, optimism and staying optimistic is the first step to actually improve things. Because the moment you convince yourself there is no solution, you will stop finding and you will stop looking for potential solutions. And I think he's right about that. I think it's important to stay optimistic despite how adverse the environment can be about this. But I am also optimistic, not only because I am trying to convince myself it's worth fighting for, but also because I've seen closely success stories in my patients and some success stories in my close relatives and actually success stories in myself. As most Mexican kids, I was a fat kid, and people joke about if you're not a fat kid in Mexico, you won't be— you won't have the right to claim a passport. I mean, it's such a— it's a staple of Mexican childhood to be at least a little bit overweight. It was my case. Everyone in my family struggled with obesity at some point of their lives, and now everyone is very near their ideal weight. I've seen lots and lots of patients drastically improve, get rid of their medications, reverse their diagnosis, acknowledge they are better by refraining from sugar and refined carbohydrates than by, by continuing their standard diets. I mean, I am optimistic, yes, because I think if you lose optimism, you will stop looking for solutions, but also because I've seen it work. So it's, it's really just a matter of don't give up sometimes. And, and something I typically say to my patients every time we are about to start a lifestyle-changing process is expect this is not going to work the first time. And even if it works perfectly the first time and you feel amazing expect you will stabilize your weight loss at some point. Expect you will need to do some changes because the diet you need to follow in 5 years is not likely to be the same diet you need to follow now. Uh, it's likely you will— that some foods you enjoyed before, you won't enjoy them as much now, and vice versa. It's a changing process. It's a knowing yourself process. And I think people actually can understand that. Some people— if you tell patients to expect mixed results in their process, they don't become disappointed when they stop losing weight so fast, or they don't become that frustrated when they can't take part in everyone's menu for Christmas Eve, or So I think I'm— I've seen it work. It's not an easy process for everyone. I'm not going to say it's a walk in the park every day, but I am optimistic because I am convinced it is important to remain optimistic, but also because I've seen it work.

And my very last question before we get into maybe more nerd stuff is, you know, how do these patients deal— we started talking about this, the cultural environment. Like what do they say to family members or friends and does it affect their social life and quality of life? Quite honestly.

I mean, it affects their social life perhaps in the very early phase of their lifestyle changing process. But after, I mean, not after much time, of course their quality of life improves and their social life improves as well because everyone starts asking them 'Hey, what are you doing? You look so much better. You are flashing new clothes.' You are— I mean, perhaps it's hard in the beginning, but not so— I mean, shortly after it becomes— they start feeling better with themselves. One of the most quickly perceived benefits they refer is they improve their sleep quality. And of course, I mean, everyone can relate with that. If you had a poor, a poor night of sleep, you feel like crap. And when you have a restful night, you feel amazing. So those things are perhaps the very first benefits people perceive. They start feeling better about that. They start feeling better because everyone is asking them what they are doing. And once they start— well, after their— I typically say, perhaps it's not super scientific, but I typically say that after their taste buds reset to the natural stimulus threshold, yes, they start enjoying more food. They start, uh, they remind themselves about this particular, uh, dish they didn't find so appealing, but now they do. And benefits set in at different times. But yes, perhaps it's hard the first 10 days, 3 weeks, but after a while they, they convince— they are convinced it's for the better.

I, I also, I love so much of what you just said, including the taste buds resetting. That I think like it's a phenomenon that anybody that's been keto for a long time appreciates. For me, it was— I tell the egg yolk story. I think you probably heard this one, but it was after a year of being keto. I'd never had anything sweet and I picked up a little bit of hard-boiled egg yolk. I thought I was eating a hard-boiled egg and I dropped some and I ate it. But it wasn't hard-boiled egg yolk. It was this yellow frosting from an ice cream cake that my family had gotten for a birthday party. And I almost gagged. It was so sweet.

And I just—

it was abhorrently sweet. But this is a frosting I used to eat by the bucketful. I used to love it. And now it's the kind of thing, it's just, you're supposed to do reset. You can have like a couple blueberries after not having something sweet and they taste unbelievable. Um, but another thing you said that made me think about, people talk about keto adaptation and fat adaptation, getting through the lull or the keto flu or getting your body into fat burning mode where you get all that energy. But what you just said, I think is the more important form of keto adaptation. That's the social keto adaptation where you go through that awkward period. Of having to say no to people and create a little bit of that conflict before you get to the benefit, the grass is greener on the other side of that's your norm. People accept that's your norm and the people that love you are happy for you and you get to be a thought leader for other people and actually attract positive social attention. I never thought about like social keto adaptation, but now I'm thinking about it as a term.

My cheeky speech And you've heard this before, and I usually say that I love non-organic food. And what I mean by that is that food is not only a source of carbon, it's not organic chemistry. Food is also a source for social interactions, a source of emotions, a source— it's particularly in Mexico a form of communication. And there is this non-carbon, non-organic part of food that is very, very important. Once you find other people who enjoy eating— I mean, once you find other people who enjoy having jungle fish salad, and once you enjoy other people who enjoy cooking with you or enjoy the things you're cooking for them, because to to pay back the embarrassment, one of the best things that could happen to anyone in Oxford was to find a small package cooked by Nick on your desk. It was an amazing cook. He's an amazing cook. So, so once you start developing that cultural and emotional aspect of food with healthier foods that keto adaptation is crucial because that's what allows you to stay with this better lifestyle for the rest of your life.

Said ironically because I didn't always bring you the healthiest foods.

Well, sure.

I mean, you, you brought me nice foods though, uh, some nice crickets. Um, anyway, that's, that's so awesome. I do want to get though into a little bit of the it wouldn't be a conversation between us if we didn't nerd out a little bit. So look, we don't have an agenda. What do you want to talk about? Insulin resistance, ketones, some of your research, including some of the unpublished stuff, whatever. Choose a topic. I mean, I don't want to—

I don't want to— because I want to get invited again. Let's not talk about everything.

So let's choose a topic.

What I was going to say, What I mildly proposed yesterday was, I think everyone— health professionals, researchers, and patients— need to rethink this concept of insulin resistance, because I think it's almost disrespectful to insulin to evaluate how good it's— how well it's working in your physiology by measuring glucose uptake. Yeah, it's, it's, it's a little bit like if I am trying to evaluate if one of my patients is healthy and I am only measuring their blood pressure. I mean, yes, part of being healthy is having safe, well, within safe range blood pressure measurements. And if you get very, very sick, your blood pressure will go abnormally up or abnormally down. But this is not the only thing you should evaluate or considering before saying somebody's healthy. I think the same is true for insulin function. Insulin is related with amino acid uptake with fat metabolism, with cell duplication, uh, metabolism and pathways, is the most anabolic hormone or message in our physiology. And to say someone is insulin resistant simply by looking at their glucose changes feels inaccurate. However, almost all our understanding and interventions that try to improve insulin metabolism are glucocentric. What I am trying to say is that I strongly believe someone can be insulin resistant and have at the same time normal glucose metrics. Yeah, what I can say is that someone can have slightly abnormal glucose metrics and have a normal insulin metabolism. Let me put, for example, uh, doing, uh, clamp studies on people following the ketogenic diet. If you have someone who follows a strict ketogenic diet and make them go into a clamp.

You want to quickly describe what an OGTT is? Assuming—

well, OGTT is an oral glucose tolerance test.

You—

and well, these are not clamps, but they deserve their own bashing because, okay, let's, let's start with the basics. People recommend Well, nutrition institutions and boards recommend people to eat less than 20 to 25 grams of sugar per day. I still think that's too much added sugar in the US. It depends on— it depends on who you're reading. In the UK is 25, uh, it, it kind of varies. I still think 20 grams a day is too much. However, someone at some point decided that the best way to evaluate your glucose metabolism was to give you 75 grams of sugar and measure your glucose over 2 hours. So let's repeat that: you're supposed to have 25 grams every 24 hours, and we assess if you were healthy or not by giving you 75 grams in 2 hours. It's like trying to see if you are fit by asking you to do in front of me 100 push-ups in 5 minutes. Not because you fail this test means your glucose metabolism— there's something wrong with your glucose metabolism. This is a completely anti-physiological way to assess glucose metabolism. It's nonsensical. And on the other hand, it assumes that the only thing or the most important thing for insulin secretion is sugar consumption or the carbohydrate content of your food. And no one really eats dextrose, spoonful dextrose. For dinner, you know, everyone's food is complex and we know, we have measured this, this is not something obscure in science. We know that the amino acid content of your food plays a huge role on your insulin secretion patterns. We know that your previous meal consumption plays a huge role in your insulin secretion patterns. We know that your exercise, we know that your microbiome play a huge role in your insulin insulin secretion patterns. So again, trying to judge if your insulin secretion is healthy or not by giving you an extremely high dose of sugar without putting these other things in context—your exercise, your microbiome, your meal before—is nonsensical. There is a very, very—I mean, this study is literally 100 years old, 1921. O-GTTs in the same subject in the same day. It's not the same curve in the morning, at noon, and in the evening. And somehow we assume, and endocrinologists assume, that this picture, these 2-hour data, will give me any insight or useful information about how is your glucose metabolism the rest of your life. It just doesn't make sense. Well, this is OGTTs. CLAMPS, on the other hand, are even worse because they don't even give you glucose via your mouth. They will inject glucose and inject insulin and try to assess your glucose metabolism with an abnormal dose of glucose. With an abnormal way of getting that glucose into your body, with an abnormal metric. Because they— the idea in a clamp is we will try to see what amount of glucose you need to keep your blood glucose concentration stable while receiving insulin, and we interpret your the, the how hungry your peripheral tissues are for glucose and how we interpret your, your peripheral insulin resistance on the amount of glucose you need to keep your glucose concentration in check.

So for a given amount of glucose, if you have to secrete more insulin, it means you're more insulin resistant. Exactly. Um, and do you want to quickly comment on that? You said the non-physiologic way of delivering glucose because earlier you were talking about Coke and then the slightly not as horrible traditional drinks that are liquid. I don't know if you want to say anything about the incretin effect. Sure. I mean, exactly.

That's, that's exactly what I was going to go because incretins were discovered when people realized— I think this was the early '70s— when people realized that you don't get the same effect if you inject 50 grams of glucose than if you drink 50 grams of glucose. People noticed that the insulin secretion pattern was more powerful when glucose was ingested or absorbed in the gut than injected directly through your veins, which was somehow counterintuitive because pharmacology teaches all med students that something is lost and that bioavailability of substances absorbed in the gut is never perfect. So it was, it was fairly counterintuitive for research at that moment that you would have more insulin secretion with a substance that was absorbed in your intestines than if you injected it directly. And that's how incretins were discovered, because gut stimulation by, in this case, glucose or other forms of food induces the secretion of these incretins, which are agonists to the glucose stimulation of the beta cells in the pancreas. So I mean, and that's why people stopped or started doing less glucose IV challenges and opted for oral glucose challenges. So both of them are a bad idea.

So insulin is like the thing that's talking, and then the incretins, if they're imbalanced, can turn up the volume on the megaphone, the amplifier.

And for example, we know, we know that some amino acids— I mean, that's, that's a great analogy. But to, to add to these, we know that some amino acids are as powerful agonists as many as other drugs we prescribe for diabetes. So for example, I don't know, sulfonilureas have a comparable agonist effect on insulin secretion as leucine. I mean, then just make sure you eat protein with your carbs and your pancreas should be fine. I mean, you don't need to reinvent the wheel and to give medications for something— a better way of mixing your foods would give So in terms of whole food proteins, are there ones that you think are meaningfully more insulinogenic?

We're talking about like fish and eggs and meat and X, Y, and Z based on the amino acid contents, carbohydrates controlled.

I mean, for sure. And again, this is not at all obscure, although I am not sure why most endocrinologists Ignore this. I think that the most important index in our foods is the insulinogenic index, the same way you have glycogenic index. And this, I mean, glycogenic meaning how much your blood glucose is raised by eating a certain food. And the standard for this is white bread, and we arbitrarily give these 100 points, uh, to white bread as the GI for white bread, and we compare things against this standard. You can do the same for insulin. So you can see how much your insulin goes up if you eat white bread and compare things against it. And this is how we learned, uh, in the early '90s that some very carbohydrate-rich foods have low insulinogenic indexes or induce low insulinogenic responses, and some low carbohydrate foods induce high insulinogenic responses. So for example, and perhaps not surprisingly, red meat is super insulinogenic, and oats are way less insulinogenic than Cheerios, and potatoes are more insulinogenic than, well, cauliflower perhaps is not too surprising. But my point is that if you want to address insulin resistance, insulin resistance, you should mind more the insulinogenic index of your foods, of your meals, than the absolute carbohydrate content. Right. You should mind more the amino acid composition of your proteins than perhaps your carbohydrate content. Because I mean, I have nothing against pea protein other than the taste, but it's, I mean, to be honest, the amino acid composition of whey protein or of red meat is just way better. If your goal is to induce a more powerful insulin response to the carbohydrates you are consuming or to the other nutrients you are consuming, you are better with a more enriched mixture of amino acids.

Yeah.

So how do you— so one of the limitations of that approach right now is that there isn't a big database of the insulinogenic index of foods.

Of course. I mean, if I ask anyone, hey, how much isoleucine you had for breakfast? I mean, people can hardly follow the carbohydrate content of their food. It would be even more difficult to add the full spectrum of amino acids to all the ingredients you use in your kitchen. That rule of thumb would be the more diverse your proteins, the better.

Yeah, I'm imagining a little pie chart right now. People have trouble like tracking their macros, usually 3 sections like protein, fat, and carbs. Imagine if like fat was broken down into like PUFA, omega-3, omega-6, monounsaturated fat, saturated fat, and then you had 20 for protein. Amino acids.

It's just impractical. And I would argue that no animal, no animal in the world needs to do that. No, I, I, I am convinced that most times you can follow your natural— this is perhaps redundant, but you can follow your instincts about food. The thing is that ultra-processed foods and the nutrient-rich environment we live now broke our instincts about what is good and what is not. So it's— the rule of thumb is the more diverse your proteins, the better.

Yeah, no, I, I couldn't agree more. I, I love the concept when applied in a natural context. It's just people say that in a completely unnatural context. It's like, if you're eating intuitively when you're eating churros, your intuition is going to be, I crave churros.

I mean, something, something, uh, that I've seen frequently, uh, once patients start to get used to these new physiological setting, or at least that's how I frame it when I talk to them, is sometimes people are surprised and say I am a little bit worried about myself because I am not hungry anymore. I am not as hungry as I was before. And of course, my, my answer typically is, that's amazing, that's great, because your hunger perception was not healthy before. I understand why this seems strange to you. I understand why you might be surprised by this less appetite. But trust me, this is your healthy appetite threshold. This is your healthy appetite perception. You were falsely and excessively hungry before. Of course you don't feel as hungry as you, as you felt then. This is actually a sign that it is working because human physiology evolved to perfectly endure prolonged times of fasting. So it is absolutely normal, and it's fantastic news that you don't feel hungry for breakfast. That's, that's just great. So it's, it's really— I'm— that's part of what I mean when I say that it is a know yourself path and process, because you need to know yourself again at these new and healthier hunger thresholds.

Right. So how would you suggest measuring insulin resistance?

I mean, I am perhaps— I am guilty of just criticizing without providing potential solutions, but I'm going to say I don't know. I'm— but I would love to get money and time to do research on it. It's, uh, I do believe we need better metrics for insulin resistance. I believe that perhaps it is a complex metric of insulin resistance. It is a composite score of fasting glucose with postprandial, uh, C-peptide, perhaps pondered by— I will actually add osmolarity changes into the mix, and I would advise everyone to go to Nick Johnson's studies about that. And I think it's very likely that the best approach is to have a composite score or complex multivariable score about insulin resistance. I think that would do— that would be a better way of making decisions. However, and that said, I am a true believer of heuristics and of rule of thumbs. Yeah. And I am sure that with enough time and money, we can provide a very complex differential equation system for predicting your glucose curve after dinner, provided we have your glucose curve after your breakfast. And perhaps that would be clinically useful someday. But at the same time, I would trust— literally, I would trust your gut, and I would trust the heuristic approach of how are you feeling? Is your sleep improving? Do you actually— I mean, people say it's amazing how frequently people say, I feel lighter. And is your GI movements better? Because some people struggle with that and then stop struggling about that once they add a right balance of fiber to their diets, regardless if they are low carbohydrate or not. So I mean, What I'm trying to say is that, yes, I can imagine how a better metric would look like, and it would be way better than what we have now. But at the same time, I'm playing devil's advocate, perhaps we don't even need one. It would be cool for nerds like us to, to, oh, I have this amazing calculator and it's super complex and it would give you your glucose curve of tomorrow. And everyone would be like, "That is so cool." But for battleground point-of-care use, perhaps we don't need that. And perhaps, uh, something I don't like of nutrition science and nutrition practice is that perhaps one of our problems is that we made these unnecessarily complicated. I don't see why we should be the only animal in the world that needs to keep track of every single ingredient of every single meal and that behaves as if metabolism was not flexible. Yeah, I think we can, we can do— it's likely that you can improve and that for most practical uses you don't need a super precise insulin measurement.

I think it was Michael Moss who coined the term nutritionism. I could be misattributing this to him, but to describe the phenomenon that, yeah, we kind of do try to break things down. You look on a nutrition label, this percent of this nutrient, this percent of that. And in breaking it down and being reductionistic, you actually— you're looking at the trees and missing the forest, which is kind of funny. And I feel like something that people who really are the biohackers and nerds come to over time. Like you want to measure all these variables and we still have fun measuring them. But in the end, you're like, I've tried to dissect this every single way I know how in my own body, in me, in an individual. And at the end of it, the most valuable thing is the biofeedback I've gotten so that now I know what being in ketosis feels like, what having a good postprandial glucose response feels like.

And then you go with that feeling. I sometimes advise patients, I mean, for those who is reasonably safe, to fast for 5 days at least once in your life. Because I think it's useful to actually feel what physiological hunger feels like. If you've never had this truly natural hunger perception. It's very easy to confuse it with routine, with anxiety, with crave. It's the first time I fasted for 4 or 5 days, I realized I had never been hungry in my life, which is, of course, I mean, it's, it's a privilege. And of course, lots of people in the world can't say this. And it's, however, is a reality and an increasing reality in industrialized countries. It is very likely that if you live in the Western world, you've never been hungry in your life, like physiology textbook hungry in your life. And it's actually useful just to have this point of reference, and the next time you feel— for example, right now I've been fasting for 30 hours, and 2 hours ago I felt hungry. But because I have this point of reference, I can remind myself, you're not hungry. I mean, this is not how you felt after 2 or 3 days. Of fasting. This is just great because a resident near you passed with some doughnuts or something like that. I mean, it's actually useful. It's actually useful to have a reference guide to remind yourself or to identify if you're hungry or not. And that's another argument, for example, against— and perhaps this is rambling now, but against counting calories. Why would we be the only animal in the world that needs to count calories to don't eat in excess? You don't, you honestly don't. And after a while of following a healthy lifestyle, you can trust your gut. And I end up telling people, and actually, I mean, as people state in Twitter, I don't have proof, but at the same time, I don't have doubts. Every time I tell a patient, or most times I tell a patient, don't worry if you're not feeling hungry, just eat when you feel hungry. Like, trust your gut. If you feel hungry, properly hungry, then eat, and stop eating once you feel satiated. Once they reach— once they've been at a healthy lifestyle for a while they never eat in excess, and they end up gravitating towards eating once, maximum twice per day. Most of them end up eating OMAD or some version of OMAD because they feel hungry once a day. Yeah. And at the same time, they don't binge on it, and they don't feel this anxiety, if I need to binge on this meal because I won't eat in another day. Again, I feel that sometimes we make fasting way too complicated because, uh, now you have a thousand apps that will keep track of your fasting and will give you pie charts and hours. And I mean, I, I am not denying they could be useful for some, and at some parts of your process, they could add value. But at the same time, you don't need that much once you have this reference of this is hunger, this is not. Yeah, you can simply trust it.

Yeah, that's nice. Um, so digging back into the insulin resistance stuff a bit though, have you seen the recent, uh, Jorgensen It was, it was in— what journal was it in? It was—

I'm not sure. I mean, there's, there's a brain insulin Nature review paper that came out as well.

I just wanted to talk about the Jorgensen came out in Endocrinology and Metabolism last month. And it was basically, it was just showing this is one more thing and then we can get to the brain insulin stuff. Of course, it's one of my favorite topics given I'm a brain guy, but that upon fasting in healthy individuals, that there's a differential response upon a whole body insulin resistance as measured by— yeah, that one. And then they have a response. The point I wanted to just make with that is that even if you're measuring, quote, insulin resistance, there's going to be tissue-specific effects. Different tissues are going to respond differently in response to fasting just because it's adaptive. Which is actually probably a good prelude to talking about the brain, because when you're fasting, it would make sense to spare glucose for the brain.

So exactly that. I mean, why glucose in your blood should tell me or should inform me about how healthy insulin metabolism in your brain is? Yeah, not because you have normal glucose after 2 hours, after a 2-hour challenge. Means your brain is not insulin resistant. There is a very nice paper, and actually it's in a radiology journal because of the techniques they used, where they tried to, to estimate which tissue contributes the most to systemic insulin resistance. Because, for example, you can— we know you can have different responses if you are liver insulin resistant adipose tissue insulin resistant, brain insulin resistant. And some of these insights come from specific knockout studies, and some come from immunology studies. And in this case in particular, they measured labeled glucose uptake in skeletal muscle, adipose tissue, the brain. They used a mixture of MRI and PET scans And first of all, their conclusion is this is likely changing in the same person after a while. But second of all, or, or the most important message I recover from that study is tissues contribute differently. I would add here, and also differently over time. Across different time points, but their consequence is not the same. I would argue that is worse to be brain insulin resistant than, for example, skeletal muscle insulin resistance.

For sure, I'd much rather have shitty workouts and not get Alzheimer's disease.

Exactly, that's, that's exactly my point. I mean, sure, so, and also because of the, the downstream effects brain insulin resistance would inflict eventually into other tissues. So that's also why I think that a composite measurement of, or estimate, multivariable estimate of insulin resistance would be better because it's clearly not enough to say your skeletal muscles are insulin resistant because again, it could just be that you are following a ketogenic diet and your muscles are supposed to be insulin resistance. So this is not surprising. This just means, this just means that your skeletal muscle is responding the way it's supposed to when or while having a ketogenic diet. I don't care about that if this means that your brain is getting more insulin sensitive. Yeah. So it's, it's too reductionistic and we base way too much importance on your isolated glucose markers.

Yeah, no, I, I think my two favorite studies that pop to mind with respect to brain insulin resistance— there was last year one by Kullmann et al. C-K-U-L-L-M-A-N-N, I think it was. I think it was in Scientific Reports. What they showed was that having an insulin-resistant hypothalamus predicted weight regain after lifestyle interventions at 24 weeks and at 9 years, which is really interesting. But another thing that was in the study is that they were saying, even controlled for BMI, that weight gain was preferentially visceral fat if you have more insulin resistance in your brain, which shows that you're— or it's consistent at least with the notion that your brain is really dictating how you partition energy. And when you're insulin resistant in your brain, not only might you have hunger cues that are off, but you're peripheral body doesn't really know how to manage that excess energy as well. Is it going to put it in muscle, fat, visceral fat? And then what are the downstream consequences? How does that cycle around? I mean, there's a huge top-down, but then there's also the bottom-up going back to the brain. I don't know if you've seen— this is my favorite paper that I've read in the past, probably. I, um, I'm gonna butcher the author's last name.

The bile acids.

Yes, the TGR5, Constantino's. Beautiful. So let's talk about it.

You start. I mean, it's, it's, it's one of these examples. Well, first of all, uh, I would love to know or to, to learn how they came up with this, like how the hypothesis started, because it's not intuitive to me in the beginning. It was not in the beginning. I mean, I can see it now, but, but Let's quickly describe what the result—

I just want to perhaps—

yeah, yeah, let's not assume, let's not assume everyone is familiar with that paper.

Yeah, so, so this paper was entitled Hypothalamic bile acid TGR5 signaling protects from obesity. It was a rodent study, and basically what they showed is that the bile acid— so we think about bile acids as like they're made in our liver for cholesterol, they're stored in our gallbladder, they're secreted to help us digest fat, that's their job. They help us digest fat in our guts. What they showed is bile acids go to the brain and signal in the brain to alter hunger, um, energy expenditure, but browning of adipose tissue and like expression of thyroid hormones. And I think it was, uh, white or brown adipocytes, insulin sensitivity, like all these things, these bile acids, these fat-digesting molecules are doing in the brain. And that actually, if you are obese diet-induced obesity, it reduces bile acids in the hypothalamus. So then you get this feedback cycle of maybe you're having an issue with bile acids, or, or, you know, being obese could actually— the state of being obese could contribute to obesity. But the main point was that bile acids, the thing that digests fat, go to the brain and signal in the brain to change insulin sensitivity for the purposes of this discussion. And with a gorgeous genetic model with that A lot of things.

Sure. I mean, it's a very carefully and well-designed study. They messed around with inhibition and activation of this receptor to prove or to show better the mechanistic response they are proposing. Their statistics are just beautiful. Their data is one of these— I like to say, or actually I wish it was my quote, But good statistics don't need hypothesis testing. I mean, you want your statistics to be that good that you don't need a p-value and you don't need a hypothesis test because it's just evident, the difference between, uh, the effects between groups. It is that kind of paper. I, I was going to say, and what I would like to say is that I typically banter endocrinologists by saying that they are experts in nothing because hormones don't exist. Because you can claim everything is a hormone. If you take the textbook definition of a hormone, a substance that's produced somewhere that acts elsewhere, well, calcium is a hormone. You store calcium in your bones and there is a calcium receptor in your kidney and in your parathyroid. And of course, my favorite hormone would be beta-hydroxybutyrate because beta-hydroxybutyrate is produced in your liver and has signaling properties pretty much everywhere else. It has different forms of regulation. I mean, you could, you can build a stronger case for BHB being a hormone than for thyroid hormones because it has so many different signaling properties. It acts at many different levels that are membrane that are directly genetic consequences, whereas for example, for steroid hormones, you only have nuclear receptors. I mean, I typically say that either everything is a hormone or hormones do not exist. Because in this case, you could say that bile acids are acting as a hormone. They have signaling properties in the brain. They are produced in your liver. And they are— they go into your bloodstream, they reach your brain, and they affect the way that tissue is responding. That said, I mean, it's, it's, it's, it's exactly, exactly, it's, it's mind-blowing. And it's, it adds to my, to my, uh, ramble and rant of either everything is a hormone or nothing is a hormone and hormones don't exist. Of course, it's an exaggeration, but what I am trying to say is physiology— it shouldn't surprise us by now that a substance produced somewhere, that because of the way medical syllabus are built and because the way physiology chapters are placed, you mentally isolate in a physiological bucket of Bile acids are digestive system. Well, guess what? You are going to find bile acids in the metabolism chapter and in the neurology chapter. And because every— I mean, it shouldn't be surprising right now— every single molecule that reaches your bloodstream is likely to have a signaling property elsewhere. And this is a beautiful example. Of something that when I was in med school was taught as, oh, this is just— this is a substance that helps you digest better your food. Well, guess what? You were being disrespectful to bile acids because they are actually a very powerful hormone with significant effects on your metabolism.

Yeah, but I don't think that— I mean, I'll tell you in a little bit if that teaching has changed. If I get into a lecture and they're like, here, we're going to talk about the neurobiology of bile acids, I'll let you know. I, I'd be very surprised to be very impressed. I'd be very surprised. Um, but yeah, it's, it's these, these, these, every molecule seems to be doing like a million and one things. And you just come to like reading this paper for me. And I think for you, it's like, you think you're kind of an ex— well, maybe you're more of an expert than I am being a, being an MD, but like you think you understand something and then you read a paper like this and you're like, whoa.

And at the same time, it makes so much sense. It does. Because why wouldn't we have evolved a way of informing your brain you have a specific form of food? Because bile acids— I mean, bile acid production and secretion are stimulated by particular nutrients, etc. I mean, it's— once you think about it, well, it makes so much sense. It's actually intuitive that, that human biology managed a way to have better responses and to collect information from the food you've just had or from the responses you've just had in your gut. It's super important. It's crucial to know what's happening in your gut. Why wouldn't you make use of what's already there?

Yeah, no, but, but it always gets more complicated. I mean, like you alluded to earlier, the, um, The day timing works. And I know something we're both interested in is like circadian rhythm. And you probably read— I think I tweeted about it the other day— the Thijas 2014, that seminal paper, the jet lag paper I call it. Yeah, they basically show like this severe, severe impact that just changing the time you eat or being jet lagged, being a night shift worker, can have on your glycemic control. And they show it's causative. You can do like the fecal transplant studies from somebody who's jet lagged or somebody who's not to mice and make the mice so beat— obese, they don't eat anymore. But you just gave them a jet-lagged microbiome and now they become obese. So there's timing and there's these ridiculous oscillations, like tenfold changes in not just the microbiome community but like where it is, the biogeography of the microbiome, like moving into the niche, moving out of the, um, endothelial niche. It becomes so unbelievably complicated. And I think And now I'm ranting a little bit, but this is what I meant by— and what I think you meant by— even the, the— I think the best biohackers, they go through it all and they're reading the literature and they come to the point that I love these data, but I also realize the most— like, I'll never ever be able to capture the data I need to overcome, to, to do more than the wisdom of my body, if I can get to that healthy place where I can listen to my body. Because there's no way I'm measuring the oscillations of my microbiome in terms of their biogeography to predict how I'm going to respond to like 23.4 grams of liver plus XYZ.

At the same time, to go back to my heuristics point, why would you need it? I mean, it's— why would we be the only species in the world that needs this amount of data? Don't get me wrong. I love data. I track everything, every single detail I can. And I love trying to see or comparing my heart rate variability between workouts. And I take blood samples every 3 months and I love data, but at the same time, I try to remind myself that data is not necessarily information. Information is not necessarily knowledge. Knowledge is not necessarily wisdom. And in this regard, if— I mean, not— you can have lots and lots of data and reach the same conclusion you would have reached with— well, I would like to say common sense, but with, with sound wisdom about your physiology. And you don't need an Oura ring to know you need to sleep and to, to take care of your sleep hours. You know, you, you really don't need that. It's nice to have it, and all of us like to nerd out about that. But I, I think that perhaps one of the most influential to my thinking, uh, lecturers, uh, I had in Oxford— one of them is Alan Garfinkel. He's a mathematician from UCLA, and he was a visiting professor at Oxford, and he gave the nerve version of the physiology course. And because it— this was mathematical modeling of physiological systems. And he has a full— the full course is in YouTube, and he has like 30 lectures there if you really want to nerd out differential equations for your physiology textbook. He's convinced that everything is oscillation and that Uh, most physiological systems can be understood better in terms of oscillation. I agree with that notion, but what I am trying to say is that because most of it is oscillation, getting one data point or getting all your data points at the same time won't give you the full picture because it's oscillation. I mean, it's— and at the same time, if your brain doesn't need a computer, well, you could— I— we can go into the debate if the brain is a computer another day. But I mean, what I am trying to say is that physiology is heuristic in a way. It's also has rules of thumb and certain patterns that if you stick to them, if you respect your feeding times, your sleeping times, and your working out times, you are actually likely to be healthy. I mean, you, you will certainly be healthy even if you're not tracking every single spoon that goes into your mouth.

Yeah. Have you heard the term allostasis? Yeah. Yeah. Yeah. Basically, it's a term that describes the— like, I'm gonna probably butcher this too, but the, like, adaptive predictability of homeostatic mechanisms. So your body's not going to just say keep your blood glucose at 90 milligrams per deciliter all the time. It actually makes sense. If you go to exercise, your body's going to want to increase it because it's predicting a particular need. And so things change over the course of the day. They oscillate based on what your body is predicting you need at certain times. It's anticipatory.

And this makes sense, like a cephalopod physiology is way too important to be left out to your human and flood.

But your body makes heuristics, they make rules. Like if you taste something sweet, it generally makes sense to release a little bit of insulin beforehand because we think blood sugar is gonna spike, so let's have the insulin there ready. And we start to break those rules the way we live. But anyway, I think all of us might need to be wrapping up. So this was always special for me. I always appreciate chatting with you. Do you have anything you want to close by saying? Where people can find you? You can plug your YouTube. I know I don't listen to it because I don't speak Spanish, but a lot about Mexico. You want to— by your YouTube and—

If any of you speak Spanish, I have a patient content-focused YouTube channel with one of my friends. It's about preventive medicine and it's called Doctor Comadre, D-R-C-O-M-A-D-R-E. And yeah, all content is in Spanish. My personal social media, I'm most active in Twitter. And I'm not that active, and I am not that much active. It's @abd_sotomota. And yeah, it's, it's been a pleasure, it's been a blast as always. Uh, again, Nick and I particularly can go about— can go like this for days. So we could—

we should try to set a world record for longer. We get like 3 Joe Rogan podcasts back to back easily.

Well, don't even attempt it. Don't even attempt it without inviting me to sit in and hang out. And we can fast through it too.

See, metabolically adapted to have the longest podcast ever.

That's right, that's right, boys. This has been amazing. Dr. Adrian, uh, Sotomayor— excuse me, Sotomayor, thank you so much for joining us. Your content's amazing and this discussion was unreal. Dr. Nick Norwitz, always a pleasure. Great job hosting, great questions. Just, I could listen to this for hours.

Oh, Adrian just got kicked out. Okay, well, I guess this is a good place to start. He says, let me relog in. This was a little bit, anyway, we were all confused about timelines and scheduled yesterday, but it's always just like, we have good chemistry and— So awesome. Awesome. And so I, I, I know he has to go see a patient now, so I'm gonna let him run off. He was super generous to give us some of his time. So, well, no worries.

Thank you so very much. And this has been another episode of Boundless Body Radio.