Transform Your Health by Improving Metabolism, Hormone & Blood Sugar Regulation | Dr. Casey Means

Welcome to the Huberman Lab Podcast where we discuss science and science based tools for everyday life. I'm Andrew Huberman and I'm a Professor of Neurobiology and Ophthalmology at Stanford School of Medicine. My guest today is Dr. Casey Means. Dr. Casey Means did her undergraduate degree at Stanford University and her medical degree at Stanford University School of Medicine. She is one of the world's foremost experts in metabolic health. Today we discuss how metabolic function and dysfunction impacts our health. In particular, we discuss mitochondria, which are involved in energy production within our cells, and the various things that we can each and all do to ensure proper mitochondrial function, which is essential not just for things like body composition and physical and mental energy, but also our ability to regulate hormones, blood sugar and much more. We discuss how exercise, even simple exercise like walking, as well as sleep, as well as more vigorous exercise and in particular nutrition, including the types of food we eat, the timing of food intake and the sources and quality of those foods, impact our mitochondria and other aspects of metabolic function. We also discuss how particular micronutrients within specific foods can directly impact mitochondrial and metabolic health. Dr. Means explains how mitochondria, inflammation and reactive oxygen species, which are the byproducts of metabolism in our cells, can combine to create conditions of obesity as well as ways that we can manage those things or even reverse biological mitochondrial inflammation and reactive oxygen species dysfunction in order to reverse obesity, reverse diabetes and enhance our health in myriad ways. By the end of today's discussion, you'll have a clear picture of the cellular processes that occur in the brain and body that underlie metabolic disease and metabolic health. And most importantly, you'll have a very clear picture of the actionable items that we can each and all carry out every day and every week in order to ensure metabolic health, proper mitochondrial function, and indeed that can also impact body composition and overall feelings of well being. I would also like to share that Dr. Casey means has a terrific new book coming out. I know it's terrific because I've read it. It is entitled Good Energy the Surprising Connection between Metabolism and Limitless Health. If you're interested in the book, we provided a link to the book in the show. Note Captions before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero cost to consumer information about science and science related tools to to the general public. In keeping with that theme, I'd like to thank the sponsors of today's podcast. Our first sponsor is Maui Nui Venison. Maui Nui Venison is the most nutrient dense and delicious red meat available. I've spoken before on this podcast and with several expert guests on this podcast about the fact that most of us should be seeking to get about 1 gram of quality protein per pound of body weight every day. Not only does that protein provide critical building blocks for things like muscle repair and synthesis, but also for overall metabolism and health. Eating enough quality protein each day is also a terrific way to stave off hunger. One of the key things, however, is to make sure that you're getting enough quality protein without ingesting excess calories. 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Now, I've spoken many times before on this podcast about the critical need to get sleep, both enough sleep and enough quality sleep. When we do that, everything, our mental health, our physical health, performance in any sports or school, et cetera, all get better. And when we're not sleeping well or enough, all those things suffer. One of the key things to getting a great night's sleep is that your body temperature actually has to drop by about 1 to 3 degrees in order to fall and stay deeply asleep. And in order to wake up feeling refreshed, your body temperature actually has to increase by about 1 to 3 degrees. One of the best ways to ensure that happens happens is to control the temperature of your sleeping environment. And with eight Sleep, it makes it very easy to do that. You program in the temperature that you want at the beginning, middle and end of the night. You can even divide the temperature for two different people. If you have two different people sleeping in the bed and it tracks your sleep, it tells you how much slow wave sleep and rapid eye movement sleep you're getting, it really helps you dial in the correct parameters to get the best possible night's sleep for you. I've been sleeping on an eight Sleep mattress cover for well over three years now and it has completely transformed my sleep for the better. If you'd like to try Eight Sleep, you can go to eightsleep.comhuberman and save $150 off their Pod 3 cover. Eight Sleep currently ships in the USA, Canada, UK, select countries in the EU and Australia. Again, that's eightsleep.comhuberman Today's episode is also brought to us by AeroPress. AeroPress is like a French press, but a French press that always brews the perfect cup of coffee, meaning no bitterness and excellent taste. Aeropress achieves this because it uses a very short contact time between the hot water and the coffee. And and that short contact time also means that you can brew an excellent cup of coffee very quickly. The whole thing takes only about three minutes. I started using an AeroPress over 10 years ago and I learned about it from a guy named Alan Adler, who's a former Stanford engineer who's also an inventor. He developed things like the Orobi Frisbee. In any event, I'm a big fan of Adler inventions and when I heard he developed a coffee maker, the Aeropress, I tried it and I found that indeed it makes the best possible tasting cup of coffee. It's also extremely small and portable, so I started using it in the laboratory when I travel, on the road and also at home. And I'm not alone in my love of the Aeropress coffee maker. With over 55,000 five star reviews, AeroPress is the best reviewed coffee press in the world. If you'd like to try AeroPress, you can go to AeroPress.com Huberman to get 20% off. AeroPress currently ships in the USA, Canada and to over 60 other countries around the world. Again, that's AeroPress.com Huberman and now for my discussion with Dr. Casey Means. Dr. Casey Means, welcome Dr. Andrew Huberman.

Thank you so much for having me.

Really excited to talk to you today about all things health. One of the things I love so much about your work is that you really give people a sense of agency through knowledge and actionable tools, which is very near and dear to My mission and my heart. But to kick things off, let's talk about metabolic function and dysfunction. I think most people hear the word metabolism and they think, okay, the burning of energy, maybe they think about ATP, maybe they think about calories in, calories out, that sort of thing. But what are we talking about when we're talking about metabolic function and dysfunction? Because these are really important concepts for everyone to understand.

Yeah, I think you're exactly right. I think that when we hear the word metabolism, the first thing that comes to most people's minds is my weight. Do I have a fast metabolism or do I have a slow metabolism or something like basal metabolic rate? And I think we're. What's really important for people to realize is that metabolism is actually the foundation of all health. It is the core foundational pathway that drives all other aspects of health. And it's also the core foundational pathway that's truly getting crushed in the modern American world and underlying 9 of the 10 leading causes of death in the United States today. It's really quite relevant to everyone. And the spectrum of metabolic rooted disease is vast and actually really relevant to most Americans. The latest research from American College of Cardiology suggests that 93% of American adults have suboptimal metabolism. And we can go into what that means. But fundamentally, when we're talking about metabolism, we're talking about how we convert food energy to human energy. So we take in a astonishing 70 metric tons or so of food in our lifetime, and that is potential energy. It's energy from the environment that's outside of us that through our metabolic pathways gets converted to a currency of energy that can then be used to pay for essentially every chemical reaction inside our body. And the bubbling up of all of those chemical reactions is our lives. And so when metabolism is not working properly, it's essentially creating underpowered cells. And like any city or factory or machine, not having adequate power will lead to dysfunction. And the reason that the metabolic spectrum of disease is so vast is because we have over 200 cell types in the body. And underpowering in different cell types is going to look like different symptoms, because underpowering in a astrocyte is going to look different than underpowering an ovarian theca cell or an endothelial cell. It's going to look different. But the core foundational process that is dysfunctional can actually be the same. And I think the biggest blind spot in western healthcare and actually the reason that health outcomes are actually getting worse every year in the United States is because fundamentally we are ignoring Metabolic health and metabolic dysfunction. We are laser focused on the downstream symptoms that result from metabolic dysfunction in different cell types. And we spend all of our energy focusing on those symptoms, playing whack a mole with them, and really ignoring that underlying foundational root cause of metabolic function. And what's so fascinating to me and what I saw in the healthcare system as like a super sub specialist, as an ENT surgeon, is that, you know, the more we specialize in healthcare, we have over 100 specialties now that we've just like invented in the healthcare system. The more we specialize in healthcare, the sicker we're actually getting. So the more we do technological innovation in all these different specialties, the sicker we're getting. And I think the real nugget there that everyone really needs to understand is we've bought into a system where we value specialization. And this is the game in western medicine. But while we've done that, what has happened is we have the worst chronic disease epidemic and the lowest life expectancy of any high income country in the world. And the reason is because in that specialization we're focused on the downstream manifestation of underpowering of cells, the cell specific symptoms and not the metabolic function itself. So really our chronic disease epidemic in this country, it is a metabolic dysfunction epidemic and underpowering epidemic. And that is the biggest blind spot in healthcare. And I think a focus on metabolic function as the center of our healthcare system. It's a completely new paradigm for health that is urgently, and I cannot overstate enough, it's urgently needed. We know we're not in the right paradigm right now when we have 100 isolated specialties and yet 85 to 90% of the conditions in those specialties, if you go to the science and look at the real physiology, is metabolic dysfunction. So that's kind of the landscape of what metabolic dysfunction is and how it's kind of creating a big blind spot in the healthcare system that really represents an outdated way of categorizing disease that unfortunately is killing us. I would say.

Yeah, thank you for that. I have several reflections and a question. First off, the analogy that comes to mind is an assembly line that's constructing, let's say, an automobile. And it sounds like 80 to 90% of the automobiles that are coming off that assembly line are not working well. Tires aren't aligned, engines isn't working well, transmission isn't working. A bunch of issues. And no factory, no car manufacturer would tolerate that, nor would the customers. But we're tolerating that in ourselves. It sounds like many People are, and then accepting the fact that then a bunch of other businesses are going to crop up, like the business that aligns the tires, the business that goes and repairs the pistons. And essentially when you talk about these multi specialties that have evolved in the medical care system, they provide an opportunity to go and fix the problems or try and ameliorate the problems. But really what we need to do to make this analogy much briefer than it otherwise would be, is just to go further up the assembly line, figure out whether or not the hardware is correct, the software is correct, and where the hardware and software are becoming deficient. In this analogy, where we are the automobile that's essentially coming off the conveyor broken. And the good news is, and I know this because I've read your book and because I follow your work very closely, the good news is that we, each and all, can take matters to some extent into our own hands, collaborate with healthcare providers and repair metabolic dysfunction, essentially make us metabolically functional. So the question therefore is, I think most people, when they hear metabolism, they think energy. And when we hear energy, we think ATP sometimes. But typically people think about mitochondria, right? The powerhouse of the cell, so to speak. So you've talked about the trifecta or the big three mitochondria, inflammation and oxidative stress, as three critical factors underlying metabolic dysfunction. And I'm presuming those are also the avenues to, to address in order to create metabolic function. Because ultimately what we want, of course, is an optimistic picture that we can actually take some control, that we have some agency in all of this, which I believe we do. So if you would, could you get us all on the same page about, you know, what are mitochondria and what do they do? Why are they so important? Then we can turn to inflammation and oxidative stress.

Yes, absolutely. So the mitochondria are the structure within the cells. We have 40 trillion cells, and each cell might have a handful or many thousand mitochondria. And they are the magical part of the cell that does that conversion process of food breaking down and then converting to energy, translating it to a currency of energy our body can recognize. And so currently what's happening is that our environment, the environment that our cells exist in across every single facet of our life over the past 50 to 75 years has changed rapidly. You look at how our food system has changed from whole real food and good soil to industrial food. Our sleep habits have changed, we're sleeping less, it's very fragmented, our movement patterns have changed. We're sitting 80% of the waking day. Our time in nature has changed. We actually are INDOORS As Americans, 93% of a 24 hour period. So that totally changes our relationship with light. We have 80,000 synthetic toxins in our food, water, air, personal care products, home care products. We live a thermo neutral existence. Now with our thermostats, there's no real swings in temperature unless you're intentionally trying to. And then our emotional health is very different. We are very much exposed to low grade chronic stress triggers. So across food, sleep, movement, emotional health, toxins, light and temperature, things are not what they once were. And it's changed in the blink of an eye. I mean, the light bulb was created in 1806. This is like 0.04% of human history that we even had artificial light. So things have changed. And the unique thing about all of these changes in our environment is that each one of those pillars, each of those changes in our environment, synergistically, directly hurts the mitochondria through different mechanisms. The chronic low grade stress, the sitting, the ultra processed nutrient, avoid food, even the blue light at nighttime, all of it through different core biologic mechanisms, synergistically hits this part of the cell, the mitochondria. So we have the food coming in, but we're not doing a good job of converting it to an energy form we can use. So we have these underpowered dysfunctional cells because of mitochondrial dysfunction caused by our environment. And of course what happens if you've got energy substrate that you can't process, it's going to be stored. And that's of course why we have in obesity, overweight epidemic that's affecting close to 80% of Americans.

So wild.

It's just we talk about obesity like it's the problem. Obesity is one branch of a tree that's rooted in this mitochondrial dysfunction that's caused by our environment. And just to back up a little bit, to just sort of share kind of maybe like how I sort of started thinking about that. You know, I had trained as an ENT surgeon and I was at Stanford Medical School. And I was so fascinated by this idea of like the way that we're defining the diseases we're treating in like a specialty. Like ENT is like I saw sinusitis day in and day out. And we'd have these patients on the table that we'd be literally drilling into their skulls to suck out sinus pus. And that's like the treatment for sinusitis. And the way we diagnose the patients is we say like, okay, this patient has sinusitis if they have facial pressure, purulent pus, you know, nasal discharge, nasal obstruction and low sense of smell. So if they have these symptoms, then they have this disease. But when you actually go to the science and you actually go to the studies of like, what is actually happening to create this, what you find is a lot of papers about mitochondrial dysfunction. Because, you know, sinusitis is in a chronic inflammatory condition where the cells are essentially sensing some threat and then they mount this immune response that creates swelling and then you get pus buildup. But we confuse the pus buildup with the disease which is actually happening inside the cells. And so you start looking at PubMed as a clinician through a slightly different lens of like, what's actually happening in the cells. And what you find for almost every chronic disease we're seeing in the US is that you will find a lot of papers on how the mitochondria are dysfunctional, lower ATP generation in a lot of these cell types. And then what does that do? And this gets to your question about chronic inflammation and oxidative stress. Well, when you've got that dysfunctional mitochondria, let's say in a nasal mucosal tissue, that is a cell that can't do its job. That is a cell that's underpowered. And what could be more threatening to the body than a cell that can't do its job? So interestingly, those cells will initiate a whole process which is called the cell danger response. It's work that's been done by Robert Navio at ucsd where basically they understand the mitochondria is not working properly. This is of course caused by the environment. And they will actually release extracellular ATP, which is not really supposed to go outside of the cell. And that creates a massive innate immune response, saying like, I'm underpowered, I need help, my mitochondria is broken. This is the cell releases ATP outside of the cell. Usually the concentration of ATP is a million times higher inside the cell, so releases it almost as a neurotransmitter. A neurotransmitter that massively activates the immune system to come and help. But the immune system comes and is like not much we can do for you here. Because the problem is not something that the immune system can help with, like grabbing a bacteria and lysing it or you know, taking care of some cells infected with the virus. The problem is outside the body, it's the environment. So you end up getting this tornado of dysfunction, of mitochondrial dysfunction caused by the environment, leading to the cell danger response, which leads to innate immunity. And then on top of this, you get the oxidative stress, which is the third piece of the trifecta, which is essentially these mitochondria trying so hard to do their work, but they're not working properly. So they create damaging metabolic byproducts called oxidative stress, free radicals that cause more damage. So this is happening in the nose, it's happening all over the American body because of our environment. So you've got these tornadoes of interrelated physiology, of mitochondrial dysfunction, chronic inflammation, oxidative stress, which, if you start going to the research as a clinician who's focused on symptoms and confusing those for the disease, and look at what's the pathophysiology of arthritis, what's the pathophysiology of Alzheimer's, dementia, what's the pathophysiology of type 2 diabetes, obesity, fatty liver disease, polycystic ovarian syndrome, erectile dysfunction. It all traces back to this trifecta that no medication or surgery. You obviously can't operate on oxidative stress. You can operate on the downstream symptoms. So that's the real secret that I really feel like we need to reorient the healthcare system around. Since 90% of healthcare costs go towards treating the downstream symptoms of these. And for every marginal dollar we're spending on treating symptoms, we. We're getting sick, the rates are going up because they're doing nothing to actually affect that trifecta. But to really make it simple, I like to think of this trifecta of what I call trifecta of bad energy trifecta, underlying metabolic dysfunction of chronic inflammation, mitochondrial dysfunction, oxidative stress. As chronic inflammation is biochemical fear, its response to a threat. Mitochondrial dysfunction is kind of like rolling blackouts. It's not enough power. And the oxidative stress is like wildfires. So it's kind of what's funny to me a little bit is like what's happening inside the cell is almost like what's happening in our society. It's like this is like living in California. It's like blackouts, fire, fear. And that's literally what's happening inside our cell because of the environment. And again, the optimistic news that you alluded to is that we actually have tons of tools and tests that can actually help us understand our level of metabolic health and even give us hints about inflammation, oxidative stress and mitochondrial dysfunction. And it's very easy to improve if we know what we're actually focused on.

Well, that's reassuring and we're definitely going to go there. I appreciate the analogy to living in California. I've lived here my entire life. I have been outside of California. But perhaps the only thing you left out, besides rolling blackouts, fires and what was the other one?

Fear.

And fear is high taxes, the taxes, the health debt on the body. So in any case, not to be too dark and pessimistic, well, that's the healthcare cost. I maintain great hope and still a lot of love for California. It's pretty great. It's got its great aspects and it's not so great aspects. And I can say that as a lifelong California resident, there are other wonderful places to live. A couple of questions. First of all about places to live you've been talking a lot about in the United States. Are some of these same issues with metabolic dysfunction occurring outside of the United States? I would imagine so, yep.

Any country where we've exported the standard American diet and some of the other norms of western living are starting to see the same rates of, of chronic disease. But like it is worth not mincing words here, of all, all high income countries in the world, the United States has the worst chronic disease rates and the lowest life expectancy. And our life expectancy is going down and we spend about twice as much on health care than the second highest spending country in the world. So we are, we are abjectly failing. And that failure is predicated in our cult of siloing conditions in into different, you know, different specialties and not focusing on this root cause. And I want to just be super clear, like there's a war being fought right now to get us to believe that siloing is the way. Because as you alluded to, siloing is profitable. If you can convince doctors and people that there are 10 different symptoms or separate things, then they're going to 10 different specialists. Office. Meanwhile, 75% of American adults are overweight and obese, some of the highest in the world. A full 50% of American adults now have prediabetes and type 2 diabetes. 50%. 30% of teens have prediabetes. 40% of Americans have a mental health diagnosis. Cancer is set to reach 2 million cases this year in 2024, highest ever in recorded history. Alzheimer's is going up. Fatty liver disease is affecting 40% of adults. 18% of teens. Autoimmune disease is skyrocketing. Infertility is going up at huge rates. All these things are going up all at Once in the US and yes, in many of the other countries that are eating our diet and there's no sign of it slowing down. And so that's really. If you look at, if you look at the research through this, this different lens, you'll find that all of those diseases trace back to metabolic dysfunction caused by our environment that no, that no shot, pill or surgery can really address unless we unpack the environmental piece.

Scary picture. I'm glad that you fix it. Exactly. I'm glad that you are creating solutions. And I should say, and just remind people I said this in my introduction, but, you know, you're talking about siloed medical care, you're talking about the kind of standard medical system, but let's not forget, right, I happen to be a faculty at Stanford. You did your medical training at Stanford. You are a medical doctor. Right. I mean, you have MD and are highly trained. You were an ent, ear, nose and throat doctor. So if anyone would be familiar with the industry and the practice and the educational system around this, it's you. So you're not speaking outside your bailiwick. So before we pivot to solutions, I know people are eager to hear solutions, but in order to understand how to best apply those solutions, I do think it's worth drilling into some of the issues here just a little bit more. You talked about underpowered cells. You've also alluded to the fact that most people are consuming enough and probably excess amounts of caloric energy.

Yes.

So is it the lack of mitochondria or mitochondrial dysfunction that's at the root of the problem? The analogy I come up with is you've got a power plant that can convert incoming power line to power that can be distributed to a community.

Yeah.

The community in this analogy being the organs and cells of the body.

Yeah.

There's plenty of potential energy, but there's something about the power plant that is inefficient or dysfunctional. Their shorts, their circuitry that's just not working, such that the energy that the community can benefit from, the cells and organs of the body is just not there. So it's not a lack of input, it's a lack of conversion and output. And the consequence of this we see in the form of excess adipose tissue and all the downstream effects. It's not just aesthetic, it's really all the downstream effects of visceral fat, subcutaneous fat, et cetera. What is it that would improve access to energy and energy utilization in cells? Is it simply a matter of getting the mitochondria to function better? Or is it that one can actually create more mitochondria?

This is the key question for how we can get healthy. And it's really about creating capacity in the body to turn more potential energy to usable energy, as opposed to taking that potential energy and shunting it to a storage form. It's all just like, I think about everything visually, and I'm like, you got the circular cell from high school biology textbook. Inside are all the little mitochondria with the squiggly lines inside. And it's just like there's X's through those mitochondria. So instead of, you know, after glycolysis and you've got the pyruvate, instead of going through the mitochondria, it's being shuttled into something else. And I mean, this is fundamentally the cause of insulin resistance, because when the body senses that the mitochondria can't do that conversion process, the cell basically says, because I can't convert this, I don't have the capacity to convert it to usable energy. I'm going to take the substrates and I need to block them. I mean, you've got to turn them to basically a storage form, which inside the cell could be toxic fats like ceramides and diacylglycerol. And I'm also going to block the cell from taking any more substrates because I can't do anything with them. That is fundamentally a root of insulin resistance. So the body says, okay, we're going to block the ability of the insulin receptor to transduce its intracellular signaling pathway. We're going to block it. And when that insulin binds, we're not actually going to allow for glucose to come in. So essentially, insulin resistance is the cell compensating for the mitochondria being broken and telling the insulin receptor that it, you know, that it's not going to be functional. And so you don't get the glute for. You don't get the glute receptors on the cell membrane to allow the glucose to come in. So that's. That's insulin resistance. Again, we talk about that as the problem, but the problem is actually inside the cell leading to that, you know, so that's why just giving someone insulin isn't necessarily the answer. We have to increase mitochondrial capacity to let the flow happen through it to energy, which then trickles up into relieving a lot of these problems. So to answer your question, what we really want to do to increase our metabolic capacity from a first principles perspective, it's we need to make more mitochondria, we need to get each mitochondria to be more functional and we need to have each more functional mitochondria processing more energy substrates. It's really that simple. And the beauty is we can do all of those things. If you actually break down what those three things mean, it means promoting mitophagy, the recycling of old mitochondria to new mitochondria. It means promoting mitochondrial biogenesis. It means increasing the oxidative capacity of our individual mitochondria. It means improving mitochondrial fusion, which is actually when mitochondria come together to form long chains of mitochondria that are more efficient. So there's like a lot of technicality to like what it means to print more mitochondria, have them each be more efficient and have each one do more work. But that's really what we want to do. And that's when it just kind of gets into the simple habits. Like there's simple things we can do for each of those things. From autophagy, you know, we can focus on various types of, like endurance exercise and high intensity interval exercise. There's compounds like urolithin A that promote mitophagy. When we talk about improving our, you know, oxative capacity, this is things like the sprint workouts, we want to build more mitochondria. This is resistance training, literally telling the body to make more. So but first principles, it's how do we get more of these working better, doing more work every day. And then we think about, you know, you look at the data on walking and it's like people who walk more than 7,000 steps a day have a 50 to 65% lower chance of dying in 10 year follow ups. And it's like, yeah, because walking is literally a glucose disposal signal. So you're just simply asking. It's not a great biogenesis signal, it's not a great mitophagy signal, but it's a great disposal. So if you're doing lifestyle habits that do one of those three things, which we can of course go into more, you're improving the cell's capacity to do that conversion process better.

I'd like to take a brief break and acknowledge our sponsor, AG1. By now, most of you have heard me tell my story about how I've been taking AG1 once or twice a day every day since 2012. And indeed that's true. I started taking AG1 and I still take AG1 once or twice a day because it gives me vitamins and minerals that I might not be getting enough of from whole foods that I eat, as well as adaptogens and micronutrients. And those adaptogens and micronutrients are really critical because even though I strive to eat most of my foods from unprocessed or minimally processed whole foods, it's often hard to do so, especially when I'm traveling and especially when I'm busy. So by drinking a packet of AG1 in the morning and oftentimes also again in the afternoon or evening, I'm ensuring that I'm getting everything I need. I'm covering all of my foundational nutritional needs. And I, like so many other people that take AG1 regularly, just report feeling better. And that shouldn't be surprising because it supports gut health, and of course, gut health supports immune system health and brain health. And it's supporting a ton of different cellular and organ processes that all interact with one another. So while certain supplements are really directed towards one specific outcome, like sleeping better or being more alert, AG1 really is foundational nutritional support. It's really designed to support all of the systems of your brain and body that relate to mental health and physical health. If you'd like to try AG1, you can go to drinkag1.comhuberman to claim a special offer. They'll give you five free travel packs with your order, plus a year's supply of vitamin D3K2. Again, that's drinkag1.com Huberman There's a lot of great science and a lot of great stuff related to testing and assessment of one's metabolic health that we should get into and will get into. But since we touched on lifestyle and because we've been talking about the sort of dysfunctional dark side for a bit, maybe we could just touch on some of the lifestyle factors that you just mentioned. Because I do think it's important that people really start to feel into their sense of agency. And here we're talking about things that are relatively low. Time investment certainly don't have much financial cost in the sense that they could be done in gyms and with fancy equipment, but they require that. Again, I want to point out that these are not like strict prescriptives, but if you had a magic wand, and because you are interested in the health of humans, let's talk about a few of these things that can improve glucose disposal and mitochondrial function. Mitophagy, the removal of dead or dysfunctional mitochondria so they can be replaced. Let's talk about the walking one first, yeah, you said 7,000 steps a day. I don't track my steps. What are we really talking about there? We're talking about taking the stairs and trying to walk as much as possible. Maybe we were going to just give a really crude prescription. You're a doctor so you can prescribe things. What would you tell people to do? How many short walks per day? Is it three? Is it five? What are we talking?

I would say at least three. I would say aiming for more than that is good though. So to sort of just give a sense of the picture of walking. If walking were a pill, it would be the most impactful pill we've ever had in all of modern medicine. There was a paper in JAMA, 6,300 participants followed for 10 to 11 years. And the people who simply walked 7,000 steps per day, compared to less than that, had in up to 70% lower risk of all cause mortality in the follow up period. So not causality, but it's pretty incredible. They've done follow up research with slightly different numbers showing again though, like many thousands of people in the study followed for about 10 years, 8,000 to 12,000 steps per day was associated with 50 to 65% lower all cause mortality. And this has been played out in many studies showing about a 50% reduction in Alzheimer's, dementia, obesity, type 2 diabetes, depression, cancer, gastric reflux, just all across the board. And I think the key thing is that it's not about the steps, it's about the fact that muscle contraction is medicine. When we contract our muscles, even in a very like low grade way, like walking or doing a couple air squats, you know, we're activating AMPK and we are essentially causing that cell to have a stimulus to push glucose channels to the cell membrane. Most of the time the glucose channels are like in vesicles in little bags inside the cells. They're not on the cell membrane. So of course that's going to keep the glucose in your bloodstream not being processed by the mitochondria. So when we think about steps, it's a proxy metric for just moving more throughout the day. So let's take two people. You have a person who's walking for one to two minutes every 30 minutes throughout the day. Maybe they're exercising at the end of the day or the beginning of the day, maybe they're not. That person is stimulating glucose channels to be at the membrane all day. Now let's take another person who works out really hard for one hour in the beginning or the end of the Day, they feel great about it, they've checked that off their box, but they're sitting the entire rest of the day. Yes, they have gotten the benefits from the exercise, but for a lot of that day those glucose channels are inside the cell not doing the work they could be doing. So I think about these little teeny short walking breaks or push up breaks, or air squat breaks every 30 minutes or so throughout the day as me essentially inside the cell, pushing the glucose channels, the cell membrane, to make them constitutively active. It's totally different physiology and it's so easy. So it's not about the steps, it's about muscle contraction regularly throughout the day. And this has been shown out in actually more clinical research which has taken. There's been several studies, two that I think are fascinating where they basically took two groups and they said, okay, we're gonna have you walk 20 minutes before each meal, three times a day, 20 minutes after each meal. So that's also three times a day or for like two minutes every 30 minutes throughout the day.

So these are three separate groups, either 20 minutes before either 20 minutes, or.

Two to three minutes every 30 minutes, all added up to 60 minutes of walking or light jogging a day. I'm kind of paraphrasing two different studies that showed the same thing. One was jogging, one was walking, but it was basically chunks versus short walks every 30 minutes throughout the waking day. The groups that do the short movement regularly throughout the day, even though the total time is the same across all the groups, have significantly lower. 24 hour glucose level averages, 24 hour insulin level averages. They are metabolically healthier. And I believe, and the research mechanistically has shown that it's because we're constitutively putting this, that these channels of the membrane to take up the substrate, use the substrate. So this is not in to, to replace exercise, but I think it's a reframe. I think the concept of exercise is something we're really very wedded to in our western culture. And you look at more like the blue zones and the centenarians and it's like they're kind of moving, is built into their everyday life. So we've taken movement out of our everyday life as these knowledge workers as we've been industrialized. And then we think that exercise replaces that all day movement, but biochemically it does not. So I think a big part of kind of digging ourselves out of this chronic disease mess and creating capacity for mitochondria is finding ways to take a lot of the activities we do now, seated and just find a way to do more of them, moving, standing or walking, or if that's tough, you really need to sit at your desk all day, then every 30 minutes, taking two minutes to do some just light movement, flex those muscles, get the glucose channels of the membrane, get the mitochondria active. So, and I think another fascinating stat is like our gym memberships in the US have doubled since the year 2000 and obesity has gone up in the same period. So there's some mismatch between our obsession with exercise and our actual outcomes that we're seeing. And I think it's that we have not actually rebuilt constitutive movement into our daily lives.

Very interesting because I think a lot of people are now working out, so to speak, doing resistance training, which I think is terrific. Terrific used to be such a, you know, so restricted to niche subculture stuff like bodybuilding, preseason football, military, etc. And now it's more ubiquitous for everybody. Men, women, young, old. That's terrific. Same thing with things like yoga and cardiovascular training. I mean, I like to study the history of exercise culture and it wasn't. But in the 60s when, you know, jogging was considered kind of like, whoa, that's like a really esoteric niche culture thing. So lots changed. I love the prescriptives you gave because it's just very straightforward, a couple of short walks. It just makes so much sense and I love the visual and I hope people will really hold it in mind. So I'll reiterate it. The translocation of these energy utilization stores, vesicles, as you call them, these little packets from the center of the cell out to the cell surface, where then they can be involved in metabolic processes and the utilization of energy in ways that otherwise they wouldn't. And glucose disposal being a big part of this. So I have heard that a short walk after a meal will reduce blood glucose in a way that's really dramatic.

Huge amount, 30, 35% just taking a walk around the block after a meal. That's definitely a prescription I think everyone should do because the research is so strong on it. Is that building in simply a 10 minute walk around the block or a dance party in the kitchen? Moving your muscles for 10 minutes after a meal can drastically reduce your glucose response because you're just bringing all those channels to the membrane, you're taking out the glucose, you're using it. It's a whole different physiology than sitting on the couch after a meal. That's very high impact. It's high Leverage if it's after a meal, so highly recommend that. And the levels data and clinical data has shown that out time and time again.

Whenever I go to a city like New York, when I am forced to walk more, I always just feel so much better. We also know that the optic flow that one experiences with walking has some interesting effects on the limbic pathways and quieting of some of the anxiety and stress related pathways. This links up with things like emdr, although there are factors that are separate from emdr. Basically moving through space, not outer space, but walking through space with optic flow has a certain anxiety reduction function in the brain, which they're beautiful data there, in my opinion. Okay, so that, that touches on walking. You did mention higher intensity exercise, so let's keep it within the cardiovascular realm for now. So getting heart rate way, way up, you know, getting breathing hard for, you know, some minutes each week, maybe a couple times per week, seems that's a good way to increase mitochondrial function and mitochondrial number. Is that right?

Yeah. So you take sort of each, each type of exercise. We've got walking, we've got resistance training, we've got high intensity interval training, we've got endurance training, and then we've got sort of more like zone two. So we've got these different flavors of how we get our heart rate up, how we get the blood flowing, what we signal to the cells. And each one actually has like a slightly different impact on the mitochondria. When we think about biogenesis, we're thinking mostly like endurance exercise and really more of that zone two. And like that is really going to be a stimulus inside the cell to print more mitochondria. When we think about improving mitochondrial fusion, high intensity interval training is really, really good for that. When we think about resistance training, it's like that's like muscle hypertrophy. We're going to be creating more muscle cells and we need more mitochondria for those. So each one has kind of a different impact. And I think this is where honestly I think the regular guidelines that we have, even by our government, you know, actually make a lot of sense. It's like work every major muscle group three times a week in a resistance type training and then work to get 75 to 150 minutes of moderate strenuous activity. So 75 minutes of strenuous activity or 150 minutes per week of moderate activity. So that actually makes a lot of sense. 80% of Americans are not meeting those very basic guidelines. And 20% of Americans don't get any physical Activity really at all activity for the average American is 3,000 to 4,000 steps per day, which is less than two miles. So we are not even close to even meeting the basic recommendations that are out there. But I think those are pretty reasonable. Resistance training two to three times a week, most major muscle groups, and working to get the heart rate up moderate level for 150 minutes a week or strenuous for 75 minutes a week. Those are going together to be potent stimuli for biogenesis, mitophagy, mitochondrial fusion for increasing antioxidant enzymes that are gonna protect the mitochondria from that oxidative stress. And the one that's just actually not in there in sort of the basic recommendations for Americans is the walking. And I would just absolutely add to that at least 7,000 steps per day based on what the data is showing, which honestly would probably take less than an hour total to do. If you break it up throughout the day, it's just a few minutes a day. So that right there are going to be like a big multifaceted set of signals for increasing mitochondrial capacity in different ways.

Terrific. What are your thoughts on under the desk treadmilling? I don't own one of these and I try and get walks and I definitely do my three resistance training sessions per week, different muscle groups on different days. So it ends up being each muscle group is hit directly once and indirectly a second time. But I like to do a long hike once on the weekend run in the middle of the week. That's 30, maybe 35 minutes and then some VO2 max, really short workout, 12 minutes total, where basically I'm just going for the feeling that my heart is going to jump out of my chest and I'm going to die from gasping of air. But luckily, thus far, I haven't died. Nonetheless, the total time commitment isn't that great. But I find that I'm at a desk a lot and I have a standing desk. Is it wise to get a treadmill to treadmill under the desk? Seems like it would be one of the best things one could do.

I'm a massive fan of under treadmill desks because genuinely I believe that if we, if we move more of our daily activities that we're doing seated indoors to outdoors moving, it would, it would ra. It would radically change the health of the United States with real physiology underneath it. So there's actually been research on under desk standing desks. That is pretty interesting small studies, but they, you know, took a handful of people. I think it was around 10 in a workplace environment. And they had them use under desk treadmills for 2 1/2 hours per day during the workday. So not a lot. At very slow speeds for two weeks. And people lost on average 2.6 pounds of fat and put on 2.2 pounds of lean mass wild in a very short period of time. The study makes a somewhat wild claim that if this were extrapolated to a year, we anticipate that we could see a loss of 44-66 lbs. How.

Assuming it's linear progression.

Exactly.

Which is not, which is not the case, folks.

But that's why I'm saying it was, it was a pretty. But that was there in the discussion. And, but I think that short period is quite interesting. So that's, that's pretty significant. And that's just for two and a half hours a day. So I think now that they're about $150 on Amazon, these under desk treadmills. I think for anyone who's a knowledge worker, it's a good thing to have at your house. And the way I use it is like I basically just force myself to start my day on the treadmill desk. And I say to myself, if I don't like it after five minutes, I'll sit down if I need to sit, but I'll start and just see how it feels. And then an hour goes by and I've forgotten I'm even on it.

Is that right? So you're able to work without thinking about having to treadmill.

I am putting it at such a slow speed, I think I'm usually walking at like one mile per hour. I mean, it's very, very glacially speaking, slow. I do put my aura ring on my second toe when I do this because otherwise it doesn't count my steps. Because if your hands are at your desk, they, they won't count your steps.

Because the OURA ring's measuring accelerometry.

Yeah, but it, it, it's incredible how Even at a 1.01 mile per hour speed, after two to three hours, you're easily going to get six, seven, 8,000 steps and then throw in a couple other short walks throughout the day and you're, you're getting there easily. So it's just a great way to build back in what modernity took away. And that unfortunately, is unavoidable, that regular movement for good physiology. So I'm a big fan of them. And the data suggests that for a couple hours a day they can actually have an impact on body composition, which I think is a great, easy, inexpensive thing for people to do. But if you don't want to buy one, just. Just set those timers and build in the walks throughout the day outside.

Terrific. I'm a fan of getting walks when I can. I wonder your thoughts on There was a study, I'm not sure if you're familiar with it, published out of the University of Houston, where they looked at what they called soleus push ups, which all the gym goers are going to roll their eyes. Imagine sitting down and pressing your toe against the ground and raising your heel. So kind of like seated calf raise, but no weight, right under the desk. And this study had some remarkable claims and conclusions which included, as I recall, that the activation of this muscle, the soleus, which makes up about 1% of the body's total musculature involved, caused rather a disproportionate use of blood glucose. So it mobilized blood glucose in a good way. And the idea was if people would it's not just bouncing your knee, but would actively push their toes against the ground and raise their heels as they were seated and doing work, that somehow there would be a positive effect on metabolism and blood glucose utilization. I talked a little bit about this on social media and a few other podcasts and it was interesting to see that sort of attacks that I got, like people really didn't like the idea that this was any different than so called NEAT non exercise activated thermogenesis. So it's known that people that fidget a lot or move around a lot burn a lot of calories. This actually goes back to some really beautiful work several decades or more ago from Rothwell and Stock, who talked about like the fact that animals and people who fidget a lot burn a lot of energy. They tend to be thinner, they tend to have lower adipose tissue stores, and it's because they're just burning a lot more calories. And this is actually what people who suffer from anorexia, which is by the way the most deadly of the psychiatric conditions so it's talking about true anorexia, are encouraged not to do because they either do it spontaneously or they learn that it's a very efficient way to burn calories. And that's not what they need. But many people do need to burn more calories. So bouncing the knee, that thing that drives everybody crazy if you're not the one doing it, Soleus push ups. What are your thoughts about this in that study? We don't have to pick it apart in detail, but I thought it was kind of interesting. It's all coming back to just moving the body as much as possible during the day. Contracting muscles.

Contracting muscles, contracting muscles. It's medicine. And I find the concept of neat just endlessly fascinating. Cause we kind of come up with this term non exercise activity thermogenesis. And the data is really good about it. It basically shows that this is a prime potential intervention for the obesity epidemic. And it all goes back to the cell. It's essentially a stimulus that's telling the body to stay, stay metabolically active as opposed to keeping all those metabolic pathways, you know, dormant during the day. And I think that it just, it is funny though that like we have these acronyms for basically like this is just the way life was a hundred years ago. If you look at like the 1800s, almost 100% of Americans lived on a farm. Basically like pre industrialization, pre urbanization. Most Americans, not 100%, but close, lived, they grew some of their own food, they lived either on a farm or had a large garden. Now that number is less than 1%. So like movement was just built into everything we did. And you think from there like what has happened, like we were outside, we were moving. Our activities of daily living involved movement. And if you just take the grocery example, then it moved to like, okay, maybe farmers markets and sort of like, you know, outdoor open air markets. Then it's supermarkets, then it's, you know, now it's literally buying food online with the click of the button. And now some people aren't even doing that. They're literally on the food delivered to them with Uber eats. So at every level we've taken away movement from everyday life and now we have sort of an acronym to like bring it back in. But really it's about just, you know, giving the body stimulus stimuli that the cells have been entrained to expect throughout all of human history and building the back into our modern life. So I neat it's incredibly important. And I think it also brings up this point that like is so critical, which is like, I really think our way out of this chronic disease epidemic and even for people who are listening, don't have a chronic disease. Any real chronic symptoms we're dealing with and just the fact that we're not feeling as good as we could. Like the way out is pretty simple. Like it's, it's some of these basic things like walking more throughout the day, moving more throughout the day, getting outside, you know, eating clean, unpoisoned food. A lot of these things that have the best data are so Simple. And I think it's like really important to just always remember, like the game and the industry, it's all about how complex can we make it. Like specialization, talking about some of the minutiae, but like at the end of the day, all the simple habits that we know are healthy, like fundamentally improve cellular biology. And like some of these things, like the neat, like the walking, like, it's emblematic of the fact that some of the simplest solutions are the ones that are by far the most effective. And I think, I think the biggest misconception in healthcare right now is that the way out and the way to get really back to true, incredible health is complicated. Like it's really not that complicated. We've got to move more, you know, throughout the day. That's one of them, you know, on each pillar that we touched on earlier, food, sleep, all of this. You know, when we talk about the simple habits that we know work, the reason they work is because they all positively impact the mitochondria, they positively impact oxidative stress, they positively impact inflammation.

So yeah, I love it. I love simple solutions that hit multiple cellular pathways that can make everybody healthier. I'd like to just take a quick break and acknowledge one of our sponsors, InsideTracker. InsideTracker is a personalized nutrition platform that analyzes data from your blood and DNA to help you better understand your body and help you reach your health goals. Now, I've long been a believer in getting regular blood work done for the simple reason that many of the factors that impact our immediate and long term health can only be addressed, that is can only be measured with a quality blood test. Now, one issue with many blood tests out there is that you get information back about lipid levels, hormone levels, metabolic factors, etc. But you don't know what to do with that information. With InsideTracker, they make it very easy to understand your levels and what they mean and specific actionable items that you can undertake in order to bring those levels into the ranges that are optimal for you. InsideTracker also offers InsideTracker Pro, which enables coaches and health professionals to provide premium and personalized services by leveraging InsideTracker's analysis and recommendations with their clients. If you'd like to try InsideTracker, you can go to InsideTracker.com Huberman and you'll get 20% off any of InsideTracker's plans. Again, that's InsideTracker.com Huberman I'd like to talk about assessment blood tests in particular. I remember in college I was just Very curious about blood testing, and I had read a little bit about it, but it was really hard to access. I actually went to the student health center and said, can I just get my lipids measured, some hormone stuff measured? I was in great health. I just want to do that. And they're like, no, what's the issue? Why would you do that? Now, it's very easy to find places that will do blood tests, but there is some cost often, and nowadays, thanks to your efforts, your innovative and engineering efforts, and the efforts of others, there are ways to measure what's in your blood, blood glucose in particular, with continuous monitoring and with snapshot monitoring. So let's talk about blood tests. What do you think are the three to five things that basically everybody, if they can, should know about what's circulating in their blood? I'm imagining ldl, hdl, this kind of thing, I guess. APOB is a big favorite of our friend Peter Attia. Fasting blood glucose, continuous blood glucose, post meal, et cetera. Just kind of evaluating how exercise, food, et cetera impacts blood glucose. And then I'll leave the other categories open because my point here is not to answer the question, but that's what comes to mind.

You know, you've got the big ones. So this, this is key, is that every single person listening, I hope after this episode will go to their health record or send their doctor a message and at least get the following test. And the first seven that I'll mention are very basic and people might take umbrage to them because obviously there's a lot of debate about, like, what's everyone's favorite lab test? But I think about it as, like, what are the basics that everyone should know? And then what's like, the next tier up that are easy to access and are cheap, that'll give you a lot more richness, but which you still might have to kind of fight your doctor for. So the first few that you will not have to fight your doctor for and are often free on an annual physical and literally define metabolic syndrome are fasting glucose, fasting triglycerides, HDL cholesterol, hemoglobin A1c, total cholesterol, waist circumference, and blood pressure.

Okay, sorry, I hate to interrupt and my audience hates it even more, but I'm going to just. Could you just explain what each of those is and what it corresponds to?

Yes, great, thank you. And I will say, first of all, the reason I'm choosing these, it's not even my own choice, really. It's two reasons One is that the two studies over the past five years that have shown us in large populations that the vast majority of American adults are metabolically dysfunctional use those biomarkers. So I think because of that, it's important to know them. And the two studies that I'm referring to are one from UNC in 2018, which showed that based on those biomarkers, 88% of American adults have suboptimal metabolism. And then a follow up study from the Journal of the American College of Cardiology from last year show that that number has gone to 93.2% of American adults are suboptimal in their metabolism. And these are the metrics that they use. And they're very basic. If you had to pay out of pocket, they would be less than $100. So let's talk through them. Why they're great is because together they give you kind of like a tapestry of what's actually happening inside the cell. If you choose to look at them that way. If you read the tea leaves of them, the doctors often, if they see all these lab tests, it'll be in an electronic health record. We've all been through this experience. They'll come up on the screen and there will either be like a green, orange or red color next to it. Like, it's high, it's low, it's borderline. And the doctor will basically, it's very algorithmic. Oh, your LDL is high, we need to bring it down. Oh, your glucose is high, we need to bring it down. Oh, your blood pressure's high, we need to bring it down. But what I'm inviting people to do is understand a little bit about each test and then read the tea leaves of what it's telling us about our mitochondria. So let's start with fasting glucose. So fasting glucose, when you look at these studies that I'm referring to, they call optimal less than 100. So to define whether you were in that 88 or 93%, you had to essentially be in the their, their optimal range for all biomarkers not on medication. So I'll quickly run through what their ranges were. My ranges for optimal are tighter than these. But fasting glucose, less than 100. Triglycerides less than 150 HDL above 40 for men or 50 for women. Hemoglobin 1c less than 5.7%. Total cholesterol to HDL ratio less than 3.5 to 1. Waist circumference less than 35 inches for women or 40 inches for men and blood pressure less than 120 over 80. If those things were in those ranges and you weren't on medication for blood sugar or blood pressure or whatnot, you were considered optimally, metabolically healthy. That's now 6.8% of Americans. All of these biomarkers are easy to change in one to two months, I would say, with simple lifestyle habits.

Could you remind us what hemoglobin A1C is? I think most people are familiar with HDL cholesterol being the, quote, unquote, good cholesterol and LDL being the bad cholesterol. And as I say that, I know I'm gonna get dogpiled. Yeah. Oh, totally. I'm not sure that I adhere to that. I'm not sure I don't adhere to that. I'm not sure about a lot of things, but I am sure that most people think of them that way. So just as a. To stay functional here, we'll frame it that way for now with the caveat that that might not be the whole story. Isn't the whole story, but triglycerides, fat in the blood, fatty stuff.

But. So key to understand about the triglycerides. It's not. We don't want to confuse triglycerides with eating more fat. Triglycerides are a storage form of excess carbohydrates in the blood. So this is why it can tell us something about. And I know you and you and Rob Lustig talked about this at length, but.

And Lane Norton and Lane.

Yeah. Yeah.

I mean, one of the things that's really tricky. Gosh. Is that the. The language around nutrition and health is complicated because people hear the word fat. They think body fat, but then they also think the macronutrient fat. We just need more words to better parse the reality in biology. We call the two major groups of people lumpers and splitters. Lumpers like to lump everything together. It oversimplifies and complicates. Splitters like to split everything, give a name for everything, individual name for everything. It complicates. And so there's a middle ground, right? There's a land of reasonable people and nomenclature. And unfortunately, that does not exist on the Internet, nor does it exist in any one specific subfield of medicine or science. I mean, so much of the confusion out in the world is because of a lack of adequate language in order to explain. Okay, so the triglycerides are a reflection of excess carbohydrate intake and how it's.

Helping us with that tapestry of Understanding the trifecta of bad energy is that if you think about it, let's just go back to that cell and that poor mitochondria that's being absolutely decimated by our environment, and its capacity is low. Okay. So that mitochondria is like, I can't process glucose or fatty acids to ATP very well, so I'm going to block their entry into the cell. So now you've got glucose rising in the bloodstream. So, okay, fasting glucose, that was one of our biomarkers. If that's going up, that is a little bit of that tapestry of maybe something's going on inside the cell that's blocking the entry into the cell. So it's rising the bloodstream. Okay, well, where's all that? The body does not want lots of glucose floating around in the bloodstream because it can literally independently cause endothelial dysfunction, which is basically blood vessel problems. It can cause oxidative stress in the bloodstream. It can cause glycation, which is sugar, literally just sticking to things. The body doesn't want that glucose high in the bloodstream, so it converts it to triglycerides to be stored in a storage form of energy. That's a key point that I think is helpful to understand, is that the body, it's always trying to, like, kind of keep things in the right range, so it'll convert things. So then triglycerides, a picture in your blood of glucose being high and triglycerides being high is very much should signal to everyone when they look at their labs that there's probably something going on inside, inside the cell that's blocking the cell from being able to use and process. It's a sign of mitochondrial dysfunction and chronic overnutrition. Too much substrate, not enough processing glucose is going to go up, triglycerides are going to go up. And so, so then if you kind of squint and read the tea leaves, it's like, huh, I think metabolic dysfunction. And what's fascinating is that the travesty in our healthcare system is that a patient might go into the doctor and their fasting glucose is 99.1point under what we'd consider the normal range. And their triglycerides are 149. One point under what we'd consider the normal range from these things that doctor might say to that patient, you're totally fine. Both glucose and triglycerides are normal, but that's just really problematic because they're on the upper end of normal for both of those. And so really what that would say to me, as someone thinking about the mitochondria is like, this person is definitely metabolically dysfunctional. They're on the highest end of normal for both triglycerides and glucose. There's something. There is definitely insulin resistance going on here. I would much rather see that glucose at 73 and that triglyceride at 50, which to me would say, oh, this cell's processing through energy, great. And things are moving through and we're not backing up in the bloodstream, we're not converting to triglycerides. So that's where really optimal ranges get in. But, but. So that's. So that's glucose and triglycerides. Why, if those are starting to creep up, it's a sign that something is happening metabolically. And then when we look at some of the other biomarkers, so hemoglobin A1C is really. So that's a marker that's looking at how many of the hemoglobin molecules that are in the red blood cells that carry oxygen, how many of those hemoglobin molecules have sugar stuck to them? And that's glycation. So you're looking at glycated hemoglobin. And you can imagine that if the concentration of glucose is higher over time, more glucose is going to stick to red blood cells and that's going to create a higher percentage of glycated hemoglobin. So that's why that lab is represented as a percentage. So less than 5.7 is what we want.

You want those cells nice and smooth.

And slippery smooth, no sugar stuck to them, causing dysfunction. And because blood cells last for about 9 to 120 days, hemoglobin A1C is giving us a basically a snapshot of average blood sugar levels over 9 to 120 days. And if that average is higher, again, probably a sign that cells are rejecting glucose from the cell and it's causing a rise in the bloodstream. And then just talking about one other biomarker in that, that we talked about, which was blood pressure, people might say, well, how does blood pressure relate to, like, what's going on inside the cell in the mitochondria and whatnot? And, and the fascinating link is that when that cell becomes insulin resistance, which again is a compensatory mechanism for mitochondrial dysfunction, the insulin is going to rise in the blood because the body's insulin resistant. So the body's going to churn out more insulin to try and overcome the insulin block, to drive the sugar into the cells. So insulin levels rise. Well, insulin is one of the key activators of nitric oxide, which is the molecule in the blood that dilates and relaxes blood vessels. And so when we become insulin resistant and we're not responding to that insulin signal, we end up getting less nitric oxide activity. So this is how, kind of looking at even these very basic, very cheap biomarkers through the lens of basic cellular physiology, we can start to see, man, my body might be, like, underpowered. I might. I might have a mitochondrial issue here. So that's a few of those tests that we really want to shoot for.

Terrific. And thanks for bringing up blood pressure again. It sort of comes across to many people as old school. Right. But when Atia was here, one of the several times he was here, he really pushed on blood pressure as such a key metric. Right. I mean, obviously, if blood pressure is high, you're getting less nitric oxide for whatever means here. Vessels and capillaries are constricted. Cells aren't able to use the energy that's coming in. There's excess energy. There's buildup of metabolic waste. There's all this stuff. And now we can start to see the picture. It's starting to emerge. And as you mentioned briefly, these markers can be put into healthy range or maybe even fantastic range in a very short period of time. So we'll talk about how to go about that in terms of getting a basic blood test. You're a physician. What's the secret code? I'll give away one that a former guest who's also an MD shared, which is oftentimes, if you ask your physician for a blood test, they will say, well, unless there's a particular need or you're struggling with something, they won't give it to you. But if you have a shift from baseline in a symptom or in a number, that can help. All the physicians are gonna come after me now with, I guess, with stethoscopes. I'm willing to stand my ground. If you want a blood test, it's often useful to mention that there's been some market shift. You want to be honest? Right. But some market shift in sleep, in lifestyle, in how you feel standing up, sitting down. I'm not trying to lace people's minds with ideas to create narratives here. But oftentimes, where physicians are resistant, they'll be more amenable if they understand that, hey, like, something's changing and the patient's saying something's changing. It actually would be irresponsible of them to not give the blood test. So there you go, bring it on. MDs.

Yeah, truly. And I think the nice thing about these, again, very basic tests. And there are so many other tests that I talk about in my book and that you've talked about on your podcast. Apob uric acid, fasting insulin, homa, ir, hscrp, liver function tests, ggt, all these other tests that are great, that can really tell us more about mitochondrial dysfunction, oxidative stress, chronic inflammation. But the ones I'm mentioning are the ones that you will not have to fight with your doctor about. Like, everything I just mentioned. Like, the doctor should order on an annual physical. And it's really about us learning to actually, like, read the tea leaves of what they're saying and not look at them in this algorithmic way. But like, how together, if they're creeping up or if many of them are a little bit high, like, we need to focus on all of our energy on improving mitochondrial capacity, basically, and bring those numbers down, which we can do very, very quickly. Once you start getting the mitochondria moving through more of those substrates, a lot of them will just naturally come down. Now, in the book, I give scripts to literally talk to your doctor with, because you are gonna get pushback often if you ask for a fasting insulin, I would say probably. I mean, even though doctors are waking up a little bit, like maybe 85% of people are gonna have their doctors say they won't order that for them. So I actually think there's a huge benefit. I hate to say it, but, like, going outside the system, this is where I think innovation has been valuable. There's a lot of, like, amazing companies doing direct to consumer lab testing. So you can basically avoid the hassle. And some of them are very affordable. There's Function Health is a company that's doing 110 biomarkers, including all the key metabolic biomarkers for less than $500. And they'll do it twice a year, so you don't ever have to. And then they do interpretations. Inside Tracker next health levels is doing labs. And so there's a lot of this springing up because I think people are sick of fighting with their doctors to get a crumb of information about their health. And it's, it's, it's. We should probably be testing these, I would say, three to four times a year. And the beauty is, is that, like, I think a lot of what keeps people down in the health world is that they're confused about what to do. There's a Lot of noise. There's a lot of different strategies. You know, do I do, you know, paleo, keto, carnivore, vegan, Mediterranean, do I do HIIT or Zone 2 or eccentric? It's like there's so much noise. And the beauty with having a plan for understanding your biomarkers regularly is that you can cut through all the noise. Try a strategy, see where you stand, retest in a few months and see if you're moving in the right direction. You don't scientist, you don't have to trust your doctor, you don't have to trust me. You don't have to trust anyone. You can literally trust your own labs. And I, I say to people, like, if your labs are optimal and the ranges I just mentioned are not optimal, like we, you want to actually get to better than all of those. If you want to be, if you're, if you're key metabolic biomarkers are optimal, if you feel absolutely freaking incredible and you have no symptoms, then you're probably doing the right strategy, whatever that is, vegan, keto, whatever, and exercise and your lifestyle, because that is showing that your cells are fundamentally working properly. So I think that's just a really empowering message. Now there's phenomenal companies that are cropping up to basically help allow people to do this on their own schedule, which I think is really the future of health and actually will help lessen, I think, some of the intensity of the diet wars, you know, because it's like people can just say, like, I trust my strategy. I know I'm doing what's right for me because, like, look at all my biomarkers and I feel great, you know.

So, yeah, what used to be the before and after, you know, pre diet, exercise, post diet, exercise photos on social media are now starting to also include numbers, which is kind of interesting. I mean, obviously these aren't randomized controlled trials, but it's cool to see people posting their numbers of things that are not just related to aesthetics, but are, or body weight, but are related to health metrics. It's fun. I think it speaks to a more scientific or at least a more quantitative approach to things, and I think it's inspiring for people. Thanks for putting those scripts in the book that people can refer to. Let's say that I go in for these blood tests, I do the basic seven, and I find that my fasting glucose is a little high, my triglycerides are a little high, my LDL is a little high, maybe a few other things are okay. So I'm kind of in the, you know, not in the red zone, but I'm in the, like I should probably pay attention to these things. What are some of the things that one can do in order to try and move those needles in the right direction? I know we talked about walking and movement before. What are a few others? And maybe we could start to touch into nutrition a little bit and then we'll pivot to insulin and blood glucose.

I think on the highest level, it's about running through what are the science based things that we know in our environment can lead to metabolic dysfunction. And take honest stock of how those factors are playing out in your life and then choose a few to start moving in a different direction. So the ones that I think are ones that we can really control and that are, we know based on the science are impacting our mitochondrial metabolic health is the food, the sleep, the movement, the emotional health, the toxins, our relationship with light and our relationship with temperature. And your journey to optimal metabolic health might be totally different from mine because I might really need to focus on the food and the sleep and the emotional health. And you might really need to focus on the toxins and the light and the movement. And so it's a lot of it is actually taking stock on where the levers are in your own life, where are you crushing it and where is there a lot of room for improvement. So step one is knowing like that those are the things, those are the things in our environment that we need to basically improve, to have to give ourselves the best capacity. And then of course, checking your biomarkers to make sure your interventions are working. But food, I think is one that is like totally unavoidable. Of those pillars, those seven pillars, food is one that most of us are getting wrong and that we really actually have to get right to improve our metabolic health for a lot of reasons. I mean, our bodies are basically 100% molecularly made from food.

That's so wild.

It's so wild.

Every time I think about that, it kind of like blows my mind.

Like babies are 3D printed from food basically inside a woman's body. It's wild to me. And then what's so cool about the body, what brings me just immense awe every day is that like we have this conception in our western world that the body is like a thing that we're with throughout our life because we kind of look the same and we like age slowly. So it's like Casey is a thing and Andrew is a thing, but the body is actually a process the body. And there's this amazing Taoist statement like life is a process, not an entity.

I love that. I'm sorry to interrupt. I'm just. I. I always wish that if people could understand that with biology and health, understanding the nouns and the names is important. But it's verbs. It's verbs, verbs, verbs. If you understand that things are processes or processes, depending on who you are and where you live in the world, it all becomes so much more tractable.

Yes. And it's so much more hopeful because if I'm a process, if you're a process, then. And every day we're eating, we are changing the process. Whereas if you think you're a thing, then there's no hope. Because I'm just. I'm Casey and that's who I am. And I have this disease, you know, And I think so much in our language, actually, of healthcare, both our Western sort of de. Spiritualized nature, like, we don't really have a lot of curiosity with process. But even, like the ideas, the way we talk about disease. I have diabetes, you know, and I. And we don't even talk about diabetes cures, which now a lot of people are curing their diabetes. We call it remission. Like it's this thing that's a part of you. And I think I just love this idea of like, we're evolving every day and food is so important because again, we take in 70 metric tons of food in a lifetime, 2 to 3 pounds per day, 1 metric ton per year on average. And that is like the printer ink, that's the 3D printer ink to create tomorrow's version of ourself, which is molecularly different than the Casey of today, that's a hopeful message. Because if we can give the body food, which, you know, I think we. Again, our conception of food, I think is very limited. Food is the molecular building blocks of the body. It is the cell signaling functional molecules that tell our cells what to do. They act as transcription factors, epigenetic modifiers, cell signaling pathway intermediates. And it's also, of course, the substrate to change what the microbiome does and the composition of the microbiome, which is basically a pharmacy inside our bodies to create different molecules that can affect our health. So food is certainly a calorie, is a calorie. From the concept of thermodynamics, but from the concept of molecular information, it has three massively important parts that are unavoidable for creating cellular health. So I would just say that that is the pillar that we can be Happy to drill into of like what do we really do to build as much metabolic health as possible?

Yeah, I want to focus now, if you're willing, on food. Not just macronutrients, proteins, fats and carbohydrates. Not just calories, although that as well, but things like timing, things like fasting and micronutrients, which I think is a highly underexplored topic. So with respect to food, gosh, I feel like we've all been exposed to pretty much every variation of it's all calories in, calories out. And by the way, I believe in the laws of thermodynamics. So yes, total caloric load matters, total energy expenditure matters without question. Within the framework of not consuming excess calories, there's a lot to explore. However, I can just say for myself, for what it's worth, I'm not very hungry until 11am noon or 1. I'm okay not eating until then and just, you know, water, electrolytes and caffeine does me just fine. I can exercise, et cetera. But once I start eating, I really enjoy eating. And I mostly like the proteins. I like meat and fish and eggs and I like cheese and vegetables and carbohydrates and fruit and all of it. I like all the stuff. And I tend to like single or few ingredient foods. I just naturally do. So I've been lucky in that way. But I know a lot of people like sandwiches, processed foods, things that are combinations of ingredients. What do we know about kind of, I don't want to say optimal, but if one, we're going to explore different ways of eating for sake of adjusting these biomarkers in the right direction and improving metabolic health? Is there kind of a generic jumping off point? Would most people, for instance, be wise to cut back on the total number of sugars or the total amount of sugar, rather perhaps reduce the amount of carbohydrate and replace it with some lean quality protein. I mean, are there generalizations that we can make or is it really all just about not getting excessive calories and trying to get those calories from the most nutrient rich sources?

Well, just drilling in on two things you just said there. So one thing you said that was interesting was that you're lucky that you like all of those foods. And then the second thing was, is it just about not getting excess calories? But I think what's interesting about both of those is that I would argue that the reason you like those foods is because you have given your body enough whole real foods that now everything in Your biology, neurobiologically, your reward circuitry, your microbiome, your satiety, hormone threshold, all of these are now basically creating a situation in which you like those foods. And then the caloric thing fits into that. Because the reason we're eating excess calories, the reason chronic nutrition is happening, and the reason we are quite literally in the United States eating ourselves to death for the first time in human history, is because we're not eating real food. And we're eating 60 to 75% of our calories of ultra processed, nutrient depleted foods that fundamentally don't give ourselves what they need. And, and a real premise that I think is so important to realize is that our cells are brilliant. And if the cells aren't getting what they actually need to function properly, they will drive you to eat until they get their needs met. Unfortunately, because the ultra processed food is designed to be highly addictive and it's devoid of what the cells actually need for good function, we end up eating ourselves into a grave. And now almost 80% of Americans are overweight or obese. Close to 50% of the country is obese. We literally gloss over this as a culture. It has become so normal in such a short amount of time. But I always think about the fact that like there are really no other animal species in the world that have obesity and chronic disease epidemics and they don't have social media, they don't have experts, they don't have PubMed, they don't have the FDA, they don't have the USDA, they don't have any of it. And they have somehow figured out a way to stay at a healthy weight and to not get heart disease. And it's because they're eating real food that meets the needs of their cells. And so I think to just boil that down, the root cause of the problem is that we have a toxic food supply that's no longer filled with the molecular information that our body needs to know to be satiated and to function properly. And so through the complex biology of satiety, hormones and neurobiology and microbiome function, we are driven to eat so, so, so much more. So truly the jumping off point for anyone on the quest to better health is to eat as much real unprocessed food from good soil as possible and of really of any dietary philosophy they want. Truly, I think if someone's eating real unprocessed food from good soil, who is, you know, plant based or who is keto, they are going to have such a higher chance of meeting their body's actual fundamental needs. And the good thing about biomarker testing is they can track for themselves if they are having good cellular function with that strategy. There's been studies that have panned this out. You know, we know that the more ultra processed food you eat, the higher risk of obviously obesity, but also chronic diseases are. But then of course there's an amazing study from Kevin hall just recently where he basically locked people up at the NIH and he, for two weeks he had them eat ultra processed food and for two weeks he had them eat real food. And people ate 7,000 more calories in the two week period when they were eating ultra processed food versus the unprocessed.

Food they were locked at the NIH. I've been to NIH quite a bit. I don't. It's great for a day job or a day visit. I don't know that I want to be locked there. That sounds like a, that sounds like the Stanford Prison Prisoner experiment.

I say this tongue in cheek and with such admiration for what he had to do. But I think it's so amusing that, you know, we have this totally frankenfood toxic food system that's largely ultra processed. And it took amazing Kevin hall to basically do an NIH funded study where people, what I say by locked is that they were inpatients at the NIH and every had ad lib unlimited access to food during each of those two week interventions. So it was two weeks of ultra processed food, two weeks of unprocessed or minimally processed food, and they could eat whatever they wanted, as much as they wanted in both groups, and then they would weigh every single bite that was left on their trays. So they knew exactly, exactly how many calories they ate. And literally just giving people this ultra processed food which is devoid of what our bodies need and therefore will drive people to eat more. They ate 500 calories more per day for a total of 7,000 calories more in that two weeks. And they gained about 2 pounds and then lost 2 pounds in the unprocessed group, which makes sense of course, because a pound is about 3,500 calories. And so we have to do these kind of crazy studies just to prove what we kind of know is true, which is that this ultra processed food environment that's cropped up for the past 50 years is an experiment that has failed. It has failed. You know, close to 45% of kids are overweight or obese now. Like it's not working. And that really is the root Cause so I think a lot of food is about quality and how do we actually really meet the needs of the cells so that our satiety hormones get secreted and we naturally stop eating. Because just telling people eat less calories but eat whatever you want, that just doesn't work. We have to inspire the body to not want to eat excess calories, which we do by stimulating satiety hormones, you know, helping the microbiome support that process and then change our reward circuitry, which is done with nutrient rich, the most nutrient rich food we can possibly get. And that's why I mentioned the soil, because our food is drastically depleted of nutrients. So when we look at that 70 metric tons of food reading in the lifetime, it's just fascinating. That's, that's the information for our body, what it's going to be built from, how it's going to function. Well, right now 60 to 75% is ultra processed. So we slash the value because the ultra processing just like slashes the nutrients, we slash the value of that 70 metric tons and then we have crappy soil because our industrial agriculture system, which means the food in some cases has 70% less of key micronutrients in it. So that 70 metric tons, what's actually useful for our body, becomes so much smaller. So what we want to do is basically expand the value of that substrate we're putting in the body. And that means real food unprocessed from good soil, meet the needs of the cells naturally, don't be hungry, maintain a healthy weight. And you know, something I talk about is that we could, I mean we could talk about nutrition, the biochemistry of nutrition all day. But in my review of sort of the biology and the biochemistry, like there's five main things I think we can strive for in our food that can really help meet the needs of our cells. And when it really comes, there are obviously more things our body needs. But if we strive for these five things, we will ultimately I think eat a really healthy diet. And that is fiber, omega 3s, adequate healthy protein, a good amount of probiotics and high antioxidant sources. And if we build our diet around knowing a few things in each of those categories that we really love and stock our kitchen with it and make our meals a mixing and matching of each of those components and we get a good amount of those, we will give the body a lot of what it needs to have mitochondrial health, reduce chronic inflammation, reduce oxidative stress.

It's interesting for me to take a step back from nutrition as it's typically presented. And think about the brain, the hypothalamic circuitry that drives hunger and satiety and things like that. And to map that onto what I've heard, and I believe to be true, based on my view of the literature, which is that we are largely meaning these circuits in the brain make us largely amino acid foraging machines because we need those amino acids in order to carry out metabolic processes and reconstruct any tissues that need repair and, and recovery, not just from exercise, but just daily turnover, removal of waste, et cetera. So we're foraging for amino acids unconsciously, we're foraging for micronutrients and of course, we need macronutrients. We need enough energy from proteins, fats and carbohydrates or some either combination of the three. I feel like I'm sort of in the dying category of omnivores, right? I'm neither. You know, I'm not meat based and I'm not plant based omnivores. I think most people are omnivores, actually. But omnivores aren't discussed quite as much as the other categories, at least not on social media. But that we think of ourselves as getting hungry and wanting to eat and I think eating the foods, some of them that I listed off before, like meat and fish and eggs and vegetables and fruits, and some I do like starches, like, like rice, oatmeal, some pastas, some sourdough breads and things. I love butter. Who doesn't love butter? Of course, none of that stuff in excess olive oil. But if one looks at kind of that buffet of options, you realize you can get some high quality amino acids, you can get some high quality lipids. You probably want to get more of them from olive oil than from butter. But you can get the micronutrients you need, provided those food sources are healthy. Now contrast that with a highly processed diet or even a minimally processed diet, and you can get the taste, you can get the macronutrients, you can get the calories, but you don't. Meaning the brain doesn't really have a sense of. It can't directly map taste, calories, micronutrients onto one another. And so you can imagine that the neural circuits, and here is a little bit of hypothesizing conjecture, but that the neural circuits responsible for hunger and satiety would get immensely confused by what's in a highly processed food, right? A Snickers bar, if you like sweets. Tastes pretty good, but it's unclear what's in it except Sugar, except, you know, it's got a certain Snickers bar taste. Right? But if the circuits of the brain are really trying to drive us to get amino acids and micronutrients for bodily health and repair, well, then highly processed and even moderately processed food has just got to be pure confusion. Sorry to go long here, but it reminds me of an idea I had once where like, imagine if you took a pill that greatly increased the level of dopamine, norepinephrine, acetylcholine and serotonin all at once. That's polypharmacology. And it might make you feel a certain way, maybe good, maybe bad. And then afterwards you'd probably have a bit of a crash from as the drug wore off. No doubt you would, but let's say you wanted more of that feeling. You wouldn't really know what to go look for because you don't know what was in it, because it's polypharmacology. So I feel like highly processed food is polypharmacology. Whereas when you are eating foods that create a more pure experience of micronutrients, amino acid content, calories and taste, those four things map to one another that intuitively we can start to understand, oh, I like this food and it's good for me and this is enough of it, right? I don't know anyone of reasonable size that eats like four rib eye steaks. They eat one. I mean, I'm sure there's some freaks out there that do that, but one even small piece of quality meat is very satiating.

Yeah, you will self regulate because the body, like every other animal in the world, is exquisitely designed to regulate hunger. On a very intuitive level, if we eat natural food, it's, you know, it's. I think it's almost ridiculous to talk about calories in isolation because the reason we're eating more calories is because we're eating ultra processed food. And so. But I love what you just said, Andrew, about the brain and the polypharmacy. I think that literally is, It's. I've never heard that said. And I think it's like processed food is like polypharmacy of food. It is the definition of processed food, which I know you talked about with Rob Lustig. The Nova 4 criteria is literally, it's breaking down foods into these constituent parts that were never meant to be separated from each other. Like the endosperm of a wheat kernel separate from the bran and the, you know, the germ. And then take that and like a little science experiment, pair it up with all these other individual components and synthetic chemicals that are made in a factory of and put them together to create this thing that the body, I truly think our insatiable hunger, again we're eating ourselves to death in the United States. That's the reality. Our insatiable hunger and our chronic disease epidemic fundamentally is a lot of it's mass cellular confusion. And when you think about what chronic inflammation is, chronic inflammation is biochemical fear on the cellular level. Well when you put this stuff into the body that's never seen before, obviously that's going to generate some confusion and you know, you could trace that back to what that really means with leaky gut and you know all the sorts of the real physiology of that. But there's a wonderful book that is called the End of Cravings by Mark Schatzer. He also wrote the Dorito Effect. But he talks a little bit about what you're talking about, which is this ideal that processed food is actually the ultimate sort of food based variable reward. So in the way that it in like things that, I mean I'm speaking expert here, but things that the body can't predict what the outcome is going to be are going to kind of get you in that dopamine motivation pathway. And that's actually what processed food is doing is it's every time we eat a different ver, we think we're eating a tortilla, but it's like completely different than all the other weird tortillas, ultra processed tortillas on the shelf. So every time we eat tortilla and our brain is this incredible prediction machine and as it's coming towards our mouth, we're predicting what the load is gonna be, but we have no idea. Is it a Coke Zero? Is it a Diet Coke with aspartame? Is it a regular Coke? It all tastes the same, but the nutrients that are gut are totally different. So we end up actually triggering the motivation pathways because of processed food representing a variable reward. Whereas every time you eat a ribeye your body's pretty much getting a similar thing each time. And so the prediction matching is going to be more conducive to getting off the motivation treadmill for more. Which I think is so fascinating. Um, but I think backing up a little bit one, one concept I have for food that really helps me is really thinking about the body's always trying to help me be satiated and trying to help reduce my cravings. I literally just have to give the body what it needs. I have to say stimulate the body in a way that it will serve me in giving me satiety hormones to basically regulate my hunger. And again, with visuals, I think it's so helpful. I think about these cells lining our small intestine that literally have nutrient sensors, like, and literal receptors on the cell membrane in the luminal side of the gut that's facing all the food that are just sitting there, like, waiting to bind with these things in our food that will stimulate the cell to make the satiety hormone that that poof effortly makes us not hungry, gets rid of that grip of attachment to cravings that all of us are so plagued by. And like, I think, you know, we have this intense conversation happening in society right now about GLP1 analogs and Ozempic and Mounjara and all these things, GLP1 agonists. But like, you know, we rarely talk about the fact that, like, we have nutrient sensing cells of the gut, the L cells of the gut that when stimulated appropriately, will make GLP1. And when stimulated the way they want to be, will secrete hordes of GLP1 for us. And so how do we actually think about just literally giving the body what it needs to stimulate the tiety hormones and the processed foods aren't giving us those things, you know, the things that are gonna stimulate those cells. Well, the things that will. I mean, this is kind of fascinating, if you don't mind going down a little road.

No, please.

Yeah, please. With the GLP1 conversation, I feel like so missing from the conversation is the idea that, like, from a first Principles perspective, there's three ways our body could make more GLP 1. We make more cells that make it L cells of the gut. Each of those cells makes more GLP1. And importantly, we can also inhibit the inactivator of GLP1, which is an enzyme called DPP4. So GLP1 actually gets rapidly degraded by DPP4 in the body. So if we can figure out how to inhibit DPP4, we can raise our GLP1 levels.

What is DPP4?

It's an enzyme that breaks down GLP1.

Thanks. I think you said that and I missed it. I apologize.

So fascinating. And so how often have you seen in the headlines, oh, here's some strategies to inhibit your DPP4? Never. Because Ozempic is, you know, on track to be the highest grossing med in human history. And just like we talked about in the beginning of the episode, the whole industry, this $4 trillion health care industry, is desperate for us to not understand how to do the things that drugs could do for us. So when we look at those three first principles, approaches of how do we make more L cells, get them to produce more GLP1 from each L cell and then inhibit the breakdown through the inhibition of DPP4. For the first one, we know that short chain fatty acids, which of course are the byproduct of microbial fermentation of fiber in the diet, stimulates the differentiation of more L cells in the gut. So more short chain fatty acids, more L cells.

Can we translate that into support the gut microbiome?

Eat more fiber.

Eat more fiber. And we had Justin Sonnenberg from Stanford on a world expert in gut microbiome. And he was a big proponent of based on work he's done with Chris Gardner and others at Stanford. So happens of ingesting one to three servings of low sugar fermented foods each day. Things like sauerkraut, kimchi. Again, low sugar variety is probably best.

Not kombucha.

Yeah, maybe not. You said not kombucha.

Yeah. Cause that's gonna be like the highest sugar of the fermented foods, which people often go to.

But not costly. The sauerkrauts. You can actually make your own sauerkraut. Tim Ferriss had a great recipe for this in the Four Hour Chef. You have to be careful because you can create some unhealthy ferment. You have to do it the way he describes. So check out the recipe. It's online. Or you can buy sauerkraut and the brines. Drinking the brine off, the sauerkraut or off seems to be good for the gut.

That's such a great point. Which is that ultimately we want the short chain fatty acids, which is the medicine that the microbiome are making for us through the microbial fermentation process. And we can basically do that in three ways. One is we can eat more fiber, which is prebiotics. We can also eat more polyphenols because we're now learning that the microbiome actually processes. They ferment polyphenols from our. Which is basically, you'll find those in colorful fruits and vegetables, spices, teas, cocoa, things like that. So fermentation of polyphenols and fiber to short chain fatty acids, which then we absorb. And then like you just said in a fermented food, the bacteria in that food will be making short chain fatty acids by fermenting the food in there. And then if we drink that, we're getting the short chain fatty acids acids directly. So that's the kimchi sauerkraut, Greek yogurt kvass, which I'm obsessed with, which is like low sugar kombucha. It's like made with fermenting beets basically. It's such good stuff. Miso natto. So that's one that has been shown to differentiate more L cells in the gut. We also know that people with type 2 diabetes have much fewer L cells in the gut. And it's hard to know what the causality is there. But I think, think a safe assumption is like if we keep our blood sugar under better control and sort of stay out of that diabetic range, it probably lends itself. I don't know what the chicken and the egg is there, but blood sugar stability, more L cell differentiation. And then actually ginseng has been shown to, to improve L cell differentiation. So that's just sort of one set of things. And I don't think the dose on ginseng has been, has been settled, but very high antioxidant component plant. When we look at actually stimulating more GLP1, you've talked about yerba mate, I think having like a mild effect on GLP1, but there's actually a lot of other things in the literature. Protein, of course, very potently stimulates these nutrient receptor cells. And specifically like valine and glutamine seem to have a potent stimulatory effect on GLP1. So interesting find that in like meat and turkey and eggs and things like that.

What are your thoughts on supplementing L glutamine? It's controversial. I know that some people do it in an effort to relieve leaky gut, but there aren't any randomized control trials for that. So depending on one's stance on what's required for kind of a threshold for adopting something, some people say that's crazy, other people really swear by supplementing L glutamine. Maybe it's through this route of increasing L cells that some of the gut relief might exist. I guess we'd have to explore it. So that's speculative, folks. So this is interesting. These are ways to increase the cells that then make GLP1. So prebiotic, probiotic fiber and fermented fats.

Antioxidants, lowering blood sugar, ginseng. So those are kind of the L cell ones. The actual secretion of more GLP1, the one of the most potent ones. And the study that looks at this like the bar graphs are very clearly statistically significant, lots of asterisks is actually thylakoids.

Thylakoids tell me More about thylakoids.

Thylakoids are so fascinating. Thylakoids are actually a structure in plants that are part of the chloroplasts. So, you know, chloroplasts. And this also is fascinating because chloroplasts are basically the plant version of mitochondria, essentially, and thylakoids are a molecule in the chloroplast. And there's actually been research that shows that when you eat about 100 grams of spinach, which gives you 5 grams of straight thylakoid, over 12 weeks daily, it led to a significant increase in GLP1. And again, I don't remember the exact. It was two or three fold higher secretion. So this is in part. So that's a direct simulatory effect of the L cells. And so this is. This equates to 3.5 ounces of spinach a day, which is like nothing.

So just getting raw spinach or cooked.

Spinach, I think I actually, I don't think it actually. It might have said in the methods, but I would. I would imagine raw because you want to get those undenatured thylakoids in the gut. So just kind of another. And actually, thylakoids do a lot of other interesting stuff. They inhibit lipase in the gut and so actually help more fat get down to the distal small bowel and promote satiety. So this is one of the reasons why you talk about, oh, the people who eat all these healthy foods and greens, they're less hungry. It's like it's biochemistry. Like, there's stuff happening in there that is making the hunger signals go down through things like inhibiting lipase, you know, improving GLP1 secretion. So other things for GLP1 secretion, the thylakoids. Also fiber has been shown specific amino acids, so high protein foods, things that involve a lot of valine and glutamine, green tea, and specifically the ec, ecgc, that is one of the compounds in green tea that's been shown to stimulate GLP1. Curcumin. So there's several things that are all in that, like whole food, you know, basically things you would associate with a healthy diet. But we actually know they stimulate GLP1. So I, you know, those are all things I try to include in my diet. And the last one is inhibition of DPP4. And that one, there's just actually, when you look at the research, there's some kind of random foods that tend to inhibit DPP4. Black beans, Mexican oregano, other forms of oregano, rosemary, guava. And I wrote this one down because it's a word I hadn't seen very much before I started digging into this. But myricitin, which is found in berries, cranberries and peppers and Swiss chard. So all that is to say, ultimately many of us are gripped by cravings and the idea of have, you know, just sort of not being constantly driven to eat more, which I would argue that about 80% of Americans are, feels really hard to overcome. But a lot of it is literally just communicating to your cells in a clear way through food to help you be satiated. And the science can show us how to do this. And a lot of it comes down to eating essentially what you were talking about, how you eat omnivorous protein, healthy sources with nutrient, you know, density, and lots of colorful fruits, vegetables, spices, herbs, things like that.

So yeah, yeah, it's interesting. Again, these aren't randomized controlled trials, nor are they peer reviewed studies. But I have a few friends who I've known for most of my life who really struggled with their weight, carried a lot of excess weight and were starting to suffer health issues in their, even their 30s, but in their 40s, I'm 48, so they're my peers and so they're about that age range. And they've all done extremely well, meaning they lost a tremendous amount of body fat, are terrifically healthy now by way of basically restricting their food intake to proteins. So fish and meat, eggs, fruits and vegetables, they basically just cut out starches. But I don't think it was the starches per se. I think it was the satiety that comes from eating high quality protein, fruits and vegetables and from limiting the number of highly processed foods. And actually the toughest thing for all of them was to, to stop asking me or themselves rather like, can I include this condiment, this, this, you know, and what's interesting is all of them now seem to really enjoy eating foods in their more pure form. And I'm not somebody that like pushes this on my friends. They just come to me and say like, how do I lose 50 pounds without having to exercise it all off? You know, as the only source of weight loss, they all exercise as well. But it's just so daunting to try and lose 20, 30, 40 pounds and to do so quickly and then to keep it off because they've all had the experience of going on a diet and then exercising a lot. The point here is that I really think there's something powerful about that relationship between taste, macronutrient value, micronutrient value, and Satiety. I think there's really those powerful associations because the brain is such an associative machine. One thing that I should have said before, and I know most people are familiar with Ozempecti. Yes, I think there's really those powerful associations because the brain is such an associative machine. One thing that I should have said before and I know most people are familiar with Ozempic.

Yeah.

And its commercial names are. I forget what the Ozempic is, the.

Commercial name and Mounjaro and Wegovy and. Yeah, got it.

Is that GLP. GLP1 acts more or less as an appetite suppressant. Powerful appetite suppressant. So many millions of people are now taking GLP1 analogs, is that right?

I think there were over 20 million prescriptions in the United States last year.

Is it expensive?

It's $20,000 per year.

Does insurance cover it?

Typically right now insurance is covering it for indications, but there is a all out assault from the pharmaceutical industry to essentially classify obesity as a genetic disease and a chronic disease in order to be able to feed this medication more into the insurance pathway and essentially get more taxpayer dollars to pay for this medication. And it is extremely expensive and it's on track to be the highest grossing medication in human history because. And it's now being recommended for people with obesity, type 2 diabetes. And then the American Academy of Pediatrics recently has talked about giving this to children as young as 12 as part of the first line for overweight. And you know, I think really it's such a travesty based on the conversation we've had, because what Ozempic does not do in any way, shape or form is impact the toxic environment that we're living in that's hurting our mitochondria. Losing weight is different than improving mitochondrial function. And mitochondrial dysfunction is the root cause of basically every chronic illness and symptom that's torturing American lives today. And so in many ways it represents like the ultimate bandaid for an environment that is not changing. And when you think about what we could do with $20,000 per year and it's a weekly injection, so people will say well per person, like oh, it's. And it's a medication that is intended to be taken for life because when people come off this medication, many people are gaining back all of the weight or even more weight afterwards. And then there's been conversations, Peter Attia's weighed in on this about loss in lean mass. You know, part of the weight loss is disproportionately muscle. And so there's a lot of concerns about it above and beyond its ability to lower the number on the scale that we should all be very alert to. Because the reality is that the 40 trillion cells in our body are in an environment in the western world right now that is not conducive to core biologic functioning. And there is obviously no shot that can mitigate the multi front assault on our biology that ultimately generates a body that, that's immensely profitable for those hundred specialties of healthcare. So we're living in this matrix and this game of a devil's bargain between a $4 trillion healthcare and pharmaceutical industry and a $6 trillion processed food industry that all want us to think that the answer is found in a shot. And we don't need to change anything about our lifestyle. But of course, these simple habits that we're talking about, eating real food, moving, walking, et cetera, getting out of and the sunlight, rapidly can increase our mitochondrial capacity and are just the most disruptive thing that we can do in our culture today is learn about metabolic health and improve it. And it's just interesting to see what's happening in the media with sort of the assault against these empowering habits and very in favor of a medication like Ozempic. And then when you trace, unfortunately incentives there a huge percentage of these outlets that cover Ozempic as a miracle drug, their bills are paid by pharma. 60% of mainstream media advertising budget is pharma. And so I just say that because I think it's a scandal that we give so much airtime to these medications and not to simple metabolic habits that can make us feel so incredible and really change our core biology.

So walking, exercise, eating minimally processed or non processed foods. You also mentioned temperature. Yeah, very, very interested in that. But before we go a little bit further down the path of what one can do in terms of having agency over their metabolic health, I just feel obligated to just entertain the possibility. Presumably somebody who's really struggled with their weight a long time, maybe because of excess cravings, you know, challenges in regulating their appetite or whatever, we don't know what the reasons are. Maybe they injured their knee and they can't exercise. I mean this happens, right? At least not yet. Take a GLP analog like Ozempic, loses some weight, probably loses some muscle also. One would hope that that would give them the sense, okay, now I can move my body better, I'll start exercising, eating better as well. I think that I have to imagine that there's a Middle case condition where people are not just relying on pharmaceuticals and not just relying on behavioral routes to improve metabolic health, but can do both. Right. I mean, and one would hope they are if they're already taking these meds. Or is it the case that when people have a pill or an injection or a potion that gives them the effect that they want, that they just remain sedentary?

I think we have to look at historians history here. I mean, first of all, there have been other weight loss medications throughout history that you've talked about on the podcast, like the fen phen. And then there was another one I think even before that that made people their temperature go up, that you can't.

Yeah, so the two. These are. I used to work on thermal regulation as an undergrad. So fen phen was eventually banned because it caused some cardiac issues. I believe it was a stimulant, fluoramine. So sorry, it's not fenfluramine alone, it's a combination of things. That's why it's called fen phen. And then dinitrophenol, which was based on the observation that workers in ammunitions factories were being exposed to this stuff and losing a lot of body fat and weight. It actually made its way into the sports community. It's highly deadly. Highly deadly. Just don't even look it up. It's highly deadly because the moment people start looking it up, they start thinking about dabbling. The way the Internet is now, dinitrophenol. And I think it has to do with sort of processing of the. Of mitochondria. I think this is happening in that the electron chains in mitochondria. So anyway, free electron. Look it up. Excuse me. The bottom line here is that there have been plenty of drugs, mostly stimulants used to help people lose weight or that have acted directly on the mitochondria. It has not worked out well historically. It just hasn't.

And I think that I'm not just gonna lump. It's a different mechanism. So I don't want to lump it in with past weight loss drugs. However, if you look at the trends throughout history, the medicalization and pharmacology towards chronic issues has been an abject failure. I don't know of and I'm sure people can correct in the comments, but of a single chronic condition for which the explosion of the pill to treat and manage that condition has lessened the rates of that condition. The more SSRIs you prescribe, the more depression we have. The more metformin we prescribe, the more type 2 diabetes rates are going up. The more Ozempic is being prescribed, obesity is going up. You know, this is on Wall Street. They're not. This is on track to be a blockbuster drug, and they're not assuming the rates of obesity are gonna go down. That wouldn't actually make sense for the business model. I mean, these are being talked about at the JPMorgan Healthcare Conferences. Do you think they're thinking that this is gonna plummet? No. Like there are. I can't think of very many chronic conditions for which the explosion of the medication has reduced the frequency of the disease. That's really something to think about. And the reason is because of exactly what we started this conversation with. Obesity is going up. You know, this is on Wall Street. They're not. This is on track to be a blockbuster drug, and they're not assuming the rates of obesity are gonna go down. That wouldn't actually make sense for the business model. I mean, these are being talked about at the JPMorgan Healthcare Conferences. Do you think they're thinking that they're not actually truly impacting or healing the root cause physiology? In some cases, they're worsening that root cause physiology. Like they are inducing oxidative stress, they may help with the symptomatic management, but not actually reducing that trifecta that we talked about in the beginning. And so why do we have reason to believe that medicalizing obesity and not actually getting at the root cause, which has to be impacted by multimodal gentle nudges in our daily life habits and environment, that that's actually gonna reduce the rates of the condition. So this is gonna plummet? No. Like there are. I can't think of very many chronic conditions for which the explosion of the medication has reduced the frequency of the disease. That's really something to think about. And the reason is because of exactly what we started this conversation with, they're not actually truly impacting or healing?

No. That's very helpful. Okay, so I'll then return to the other question about temperature. What are some things that can do with temperature? And by the way, as I do this, I can't resist any longer. Casey, Dr. Means brought me this jar of blueberries. People that know me know that I'm a drive by blueberry eater. So if there's blueberries out on a table, I'm gonna take some. I've never eaten during a podcast, but I'm going to now, so. So I'll try and chew quietly. Do you want some?

Sure.

I love blueberries. And no, I don't eat them one by one, but I'm going to try and eat them quietly. So we'll keep them here in the middle for the time being and I'm going to eat them by the handful just because I got hungry. And you mentioned berries earlier and it triggered a neural circuit for me. So what about temperature?

People that know the root cause physiology, in some cases they're worsening that root cause physiology like they are inducing oxidative stress, they may help help with the symptomatic management, but not actually reducing that trifecta that we talked about in the beginning. And so why do we have reason to believe that medicalizing obesity and not.

Me or even that just listen to the podcast, know that I like the cold shower thing, cold plunge thing. I don't do it every day. I don't do it after resistance training workouts for at least six hours and mostly keep it on days separate from the resistance training because there are some data that can inhibit hypertrophy and strength adaptations. But I like it. I like it. It feels good. I feel great afterwards for many hours. And I believe there are some health effects. And I'm willing to weather the storm of naysayers because more and more data keep emerging that that's the case. Not all the data are spectacular. One paper on this actually was just.

Not actually getting at the root cause which has to be impacted by multimodal gentle nudges in our daily contracted.

We need to do an update to an episode to it's not work for.

My lab but life habits and environment that that's actually going to reduce the rates of the condition.

So no, that's very helpful. Okay, so I'll then return to the other question about temperature. What are some things? I still think that there's a lot of really terrific work on deliberate cold exposure. What's the deal with temperature and mitochondria?

So no one has basically described this better than you, I feel like on your platform. But I think about it very, very simply. Throughout human history, humans have really in so many different parts of the world been exposed to hugely fluctuating temperatures. Like if you look at the Sahara Desert or like a regular day in Colorado, it's like you can go from, let's talk about Sahara Desert. You can go from 30 degrees to 110 degrees in the span of one day. And like even the concept of indoors is like a relatively new can do a temperature.

And by the way, as I do this, I can't resist any longer new.

Concept in human history. Four Walls, you know, insulation, then central heating and cooling. That's like the last 50, 75 years in most homes. And so this idea, our cells have evolved.

Casey, Dr. Means brought me this jar of blueberries. People that know me know that I'm a drive by blueberry eater. So if there's blueberries out on a table, I'm gonna take some. I've never eaten during a podcast, but I'm going to now, so I'll try and chew quietly. Do you want some?

To respond to big swings in temperature that very recently we have totally pulled away. And I think that when I think about the mitochondrion increasing their capacity, I'm thinking about, well, how do I use different energetic signals in my environment to essentially get the mitochondria to do better work? And we can think about all the different types of energies that we're exposed to. Solar energy, thermal energy, acoustic energy, mechanical energy, you know, food energy. Like there's, there's. That's basically what our environment is.

I love blueberries. And no, I don't eat them one by one. So I'm. But I'm going to.

Is right. And thermal energy is a big one of those. We can speak to our mitochondria with the language of thermal energy and say, hey, it's cold outside.

We need try and eat them quietly. So we'll keep them here in the middle for the time being. And I'm gonna eat them by the handful just because I got hungry. And you mentioned berries earlier and it triggered a neural circuit for me. So what about temperature?

People that know you to print more of yourselves or work harder such that we can create heat inside the body to respond to this meat or even that.

Just listen to the podcast, know that I like the cold shower thing, cold plunge thing.

I don't do stimulus. And so that's kind of the framing that I use for it. And like, you know, this data is hard to know if it's totally accurate, but like, our population is. Is cooling and some. I think it was data, Stanford, actually, that was showing that, like our temperature has gone down like 2% or something like that in the last hundred years. And that fundamentally is mitochondria not working as well as they should. Research has shown we're making less ATP in a lot of our cells, and that's, you know, a function of mitochondrial dysfunction.

Do it every day. I don't do it after resistance training workouts for at least six hours.

One fun fact. I don't know if you knew this, but the body makes about 88 pounds of ATP per day for like the average American. So we're constantly making it ours and.

Mostly keep it on days separate from the resistance training because there are constantly.

Recycling it in this, like, you know, like basically make it, use it, make it, use it, make it so fast.

Some data that can inhibit hypertrophy and strength adaptations. But I like it, I like it. It feels good. I feel great afterwards for many hours. And I believe there are some health.

That like we essentially don't change our weight, but it's kind of. And of course, as it's being broken down HP to adp, we release heat. And so I just think of cold as like one of the tools in our tool belt to talk to the mitochondria to say make more heat. And in a world in which our mitochondria are under siege, I think it's a valuable, often very inexpensive one that we can use. Of course it does not supplement or replace food, sleep, exercise effects.

And I'm willing to weather the storm.

But I think it can be a very valuable tool to stimulate through that signal to basically make more heat. And we know of course it can help. And the data is mixed.

Of naysayers because more and more data keep emerging. That's the case. Not all the data are spectacular. One paper on this actually was just.

Like increased brown fat, which is like mitochondrial dense fat.

We need to do an update to an episode to to. It's not work from my lab, but.

Have it do more work and whatnot. So ultimately brown fat is mitochondrial dense fat and we want to help promote that. So that's how I use cold. And then on the heat side, just fascinating how that's kind of acting to help metabolic health through the activation of the heat stock proteins, some of which have the ability to upregulate antioxidant defense systems and quell some of that wild.

I still think that there's a lot of really terrific work on deliberate cold exposure. What's the deal with temperature and mitochondria?

So no one has basically described this better than you, I feel like on your platform. But I think about it very, very simply. Throughout human history, fire that we talked about, that can hurt our mitochondria. So I put them lesser on my list. But you know, cause we just can't. We can't avoid the food and, you know, the sleep and the movement. But I think it's a great tool.

That we can use and I love it. I will just point out that the reason the brown fat is brown at all is because of the density of mitochondria. Literally brown down the microscope. This is not the kind of fat that is subcutaneous, although it sits around the scapula, neck, upper back. There's other pockets of it on the body, too. And such an interesting tissue. Yeah. I don't know why deliberate cold exposure is so controversial. I think it's because people who don't like it, and frankly, no one likes getting in it.

Humans have really, in so many different parts of the world, been exposed to hugely fluctuating temperatures. Like, if you look at the Sahara desert or like a regular day in Colorado, it's like you can go from. Let's talk about Sarah Desert. You can go from 30 degrees to 110 degrees in the span of one day. And like, even the concept of indoors is like a relatively new.

The best part is getting out and how you feel afterwards. But I think it. Nothing grates on people like deliberate cold exposure if they don't like deliberate cold exposure. And there's no requirement for it. But I think it's a very interesting stimulus. And I think there's also a very interesting relationship between light and temperature, because in most areas of the world, as days get longer, meaning more sunlight available, temperatures go up. And nowadays we can really divorce ourselves from all this, like day lengthening and shortening temperature fluctuations. Which is not to say that we should all be running around in minimal amount of clothing outdoors. But there's just such Beautiful data from Dr. Susannah Soberg's work showing, for instance, that deliberate cold exposure then leads to one feeling more comfortable at cold temperatures.

New concept in human history. Four walls, you know, insulation, then central.

Heating, because you become essentially more of a furnace, more warm and cooling.

That's like the last 50, 75 years in most homes. And so this idea, our cells have evolved more brown fat.

Anyway, we could go on and on, But I think it's yet another lever of autonomy in terms of taking control of one's health. As you said, not as critical as food intake and quality, amount, and maybe.

Timing to respond to big swings in temperature that very recently we have totally pulled away. And I think that as well.

Speaking of timing, what are your thoughts on fasting? And then, of course, movement and exercise. Yeah.

The way I conceptualize the idea of fasting, obviously this is one where we need more words. Right. Because the word fasting is so limited. There's so many different parts of this.

But skipping breakfast for me would be that. Or skipping dinner. Sometimes I'll skip dinner. Sometimes I'll skip breakfast.

Right. I, when I think about the mitochondria and increasing their capacity, I'm thinking about, I think that some of the most interesting data that I've seen has been about if we reasonably compress our eating into daytime hours during the heart of the diurnal cycle when we are supposed to be eating. So essentially matching our chronobiology with our behavior, which you know, we are diurnal organisms so we kind of need to respect that like when we. Well how do I use different energetic signals in my environment to essentially get the mitochondria to do better work? And we can think about all the different types of energy that we're exposed to. Solar energy, thermal energy, acoustic energy, mechanical energy. We do that and we compress it in a moderate way. Our metabolic health is better. And so some of the studies that have looked at this one that was interesting was, and I think very hopeful for people is that if you take all the food, all the calories that you're going to eat and eat them in a six hour window, you know, food energy, like there's, there's, that's basically what our environment versus a 12 hour window. Totally same amount of calories, exact same food. This is a controlled experiment. People who eat the same amount of calories in a six hour period are going to have much lower, statistically Significantly lower glucose, 24 hour glucose and insulin levels compared to people who just is right. And thermal energy is a big one of those. We can speak to our mitochondria with the language of thermal energy and say hey it's cold outside, we need you to print more of yourselves or work harder such that we can create heat inside the body to respond to this, space it out over the course of a 12 hour period. And it makes sense because if you're spacing that food out over the course of 12 hours, that is a different biochemical mil you in your body throughout the day. It's kind of similar to the walking, you know, it's like you are then stimulating insulin several more times. You are exposing the bloodstream to insulin and glucose just more throughout the day and giving the bloodstream less of an opportunity to sort of be clear from that glucose and that insulin. And so compressing our eating window seems to be helpful for, for metabolic health. And it's a bang for your buck. Right. Like you could stimulus. And so that's kind of the framing that I use for it. And like, you know, this data is hard to know if it's totally accurate. But like our population Is is cooling and some. I think it was data Stanford actually that was showing that like our temperature has gone down like 2% or something like that in the last hundred and that fundamentally is mitochondria not eat the same amount of food. You just have to eat in a shorter period of time. So for people who want to eat, you know, a lot, maybe just consider compressing it into daytime hours, six to eight hour window.

Yeah, for me six is tough. The one meal per day thing is tough. I have friends like Lex Friedman that do the one meal per day thing. I end up eating so much food at that meal that I experience a lot of kind of like mechanical distress as typically later in the day. I think an 8 to 10 hour window has worked well.

Working as well as they should. Research has shown we're making less ATP in a lot of our cells and that's a function of mitochondrial dysfunction.

Well for me most days. I know as soon as we talk about intermittent fasting which is what or time restricted feeding, same thing which is what we're talking about right now. I'm sure somebody's going to call up the. There's been a study that's been circulating about a massive increase in cardiovascular risk in people doing intermittent fasting in particular.

The sickening one fun fact, I don't know if you knew this but the body makes about 88 pounds of ATP per day for like the average American. So we're constantly making it and we're constantly recycling it in this like, you know, like basically make it, use it, make it, use it, make it.

So fat sour eating window. I just want to point out worst study as far as I know I could be wrong but as far as I know that study is still in abstract form, it's not yet peer reviewed. It's like the fact that studies that haven't been peer reviewed aren't even close to being peer reviewed, are being put out there as news stories is really problematic because I can tell you as somebody who sat on the editorial boards of many journals for many years, I still sit on a few, reviewed countless papers I've submitted and had to deal with reviews on countless papers. The fact of the matter is until the reviews are done, the revisions are made, like that paper may never see the light of day and it may end up in a journal that you is barely worthy of a place mat. It might end up in a high.

Test that like we essentially don't change our weight but it's kind of. And of course as it's being broken down HP to adp, we release heat. And so I just think of cold as like one of the tools in our tool belt to talk to the mitochondria to say make more heat. And in a world in which our mitochondria are under siege, I think it's a valuable, often very inexpensive one, high quality journal.

But it might not. So just because there was, quote unquote, a study done means very little, but it means especially little, maybe nothing until it's peer reviewed.

Absolutely. And the methods were very poor in that study. It was a recall based study I think for two days of recall of people's diets, which is notoriously very bad in terms of accuracy. So yeah, and I think I'm not in any way suggesting that a six hour window is the optimal window. I'm just sharing that can we can use. Of course it does not supplement or replace the data that suggests that compressing the window seems to have a favorable effect. And I certainly don't do six hours. But I think when you look at what the, the average American is doing, which is the Average American has 11 eating events per day and food, sleep, exercise, 50% of Americans eat over a 15 hour window per day. But I think it can be a very valuable tool to stimulate, you know, through that signal to, to basically make more heat. And you know, we know, of course it can help. And the data, you know, is, is mixed. But like I can recall those because I remember when I was writing the book I, I was like that's a long time, 15 hours and 11 events. And, and every time you're doing that, you're going to be stimulating this glucose rise in the bloodstream exploits, exposing the blood vessels to that glucose. You're going to be turning on all the pathways with insulin to basically store it or you know, and it's so it's, it's straight like increase brown fat, which is like mitochondrial dense fat and for the body. And so I think giving the body times intentionally to allow insulin to come down and to allow glucose to come down. What that does is it generates metabolic flexibility. It gives our body an opportunity to have space to use accessible gluten, have it do more work and whatnot. So ultimately brown fat is mitochondrial dense fat and we want to, you know, help promote that. So that's how I use cold and then on the heat side, you know, just fascinating how that's kind of acting to help metabolic health through the activation of the heat stock protein coast and then convert into using stored fat. But be and that ultimately is Metabolic flexibility, the ability for the body, giving the body opportunities to use glucose, but then have times when there's not high glucose and insulin around to actually get into the fat stores. And I think one of the reasons why we have such a massive overweight and obesity, you know, rates in the country is because some of which have, you know, the ability to upregulate antioxidant defense systems and quell some of that wild. Because with the way the culture of eating right now, 11 eating events per day, eating over the course of 15 hours per day, I would imagine the average American body is rarely if ever tapping into their fat stores for energy in a meaningful way because we always have glucose available that we talked about that can hurt our mitochondria. So. So I put them lesser on my list. But you know, because we just can't, we can't avoid the food and you know, the sleep and the movement. But I think it's a great tool that we can use bulge the body. If you think about again, the stats about ultra processed food, about 70% of the items on the shelves in the grocery store are ultra processed food. And those ultra processed foods are built on refined added sugars and refined added grains. So we're just, we very rarely give the body the opportunity to rest and move into fat burning. And that's where compressing the eating window can be valuable. Obviously people have talked about this before, but fasting can be a stressor for the body.

I love it. I will just point out that the reason the brown fat is brown at all is because of the density of.

Mitochondria, especially if your body's not used to using fat for energy. And so it's something to ease into and go slow. But I think if you're slowing down enough to really hear what you're literally.

Brown down the microscope. This is not the kind of fat that is subcutaneous, although it, you know, it sits around the scapula, neck, upper back. There's other pockets of it on the body too. And such an interesting tissue. Yeah. I don't know why deliberate cold exposure is so contrary.

Body signal are saying, you can kind of know whether I think you're fat, fasting is working for you or not. I can tell if I've got too many other things going on. I haven't slept well, a lot of stress. I can tell that fasting is kind of making me jittery and not feel good versus if I'm really, if I have good capacity, I can feel that it's actually making Me feel really incredible. And so tune in with your body obviously and you know, you can check your biomarkers. If you have a CGM on, you can see what's happening in your glucose. If you have a ketone monitor, you can see what's happening to your ketones and really actually track which I think makes fasting actually even, even more fun. I'll mention one other piece of data that I think is actually really kind of fun as well with timing of eating. There was a study that looked at people who ate the exact same meal at 9:30am or I think it's because.

People who don't like it and frankly no one likes getting in it. The best part is getting out and how you feel afterwards. But I think it's nothing grates on people like deliberate cold exposure if they don't like deliberate cold exposure and there's no requirement for it. But I think it's a very interesting stimulus and I think there's also a very interesting relationship between light and temperature.

Because in most areas 8:30pm so basically after dark, essentially in the part of the diurnal phase when we probably shouldn't be eating versus early in the morning, 9:30. And the glucose and insulin responses for the same meal at 8:30pm were significantly higher than when eating at 9. And so again, bang for your buck. It appears that eating in that earlier part of the day when we're active and our chronobiology is set up for metabolism and activity, we have a lower glucose and insulin response. There's also some evidence that melatonin, which is secreted as we get closer to sleep, has somewhat of an effect on impairing our insulin sensitivity transient. And so we may actually of the.

World as days get longer, meaning more sunlight available, temperatures go up. And nowadays we can really divorce ourselves from all this like day lengthening and shortening temperature fluctuations. Which is not to say that we should all be running around in minimal amount of clothing outdoors, but there's just such Beautiful data from Dr. Susannah Soberg's.

Work just be not absorbing the glucose from those meals effectively later at night. So I tend to kind of move a little bit more, a little bit more low carb I would say throughout the day based on that data and what I've seen on my continuous glucose monitor. Basically just higher spikes for the same meal later in the day. So why not just kind of move it up earlier?

Very interesting. Something I'll definitely try. I tend to push my carbohydrates to a little bit later in the day for sake of sleep. Unless, of course, I've done resistance training, which I do three times. I aim to do three times a week. And post resistance training, I try and get some starchy carbohydrate in me just to replenish glycogen. And that then tends to reduce my carbohydrate craving later in the day. I love bread and butter. Bread and olive oil pasta. Showing, for instance, that deliberate cold exposure then leads to one feeling more comfortable at cold temperatures. The other day I found this Argentine place and I love the steaks there. But they had gnocchi that it took everything I had, every neural circuit in that releases GABA inhibition to my brain to not order three of those orders. It was so good.

But you can walk after the gnocchi.

Oh, yeah, sure. I'll allow myself to do those things. I'm not. Because you become essentially more of a furnace, more brown fat. Anyway, we could go on and on, but I think it's yet another lever of autonomy in terms of taking control of one's health. As you said, not as critical as super restrictive. But again, I tend to eat, eat high quality foods. By the way, these blueberries are amazing. Then you figure out where you got those because they're just tangy enough. I'm doing everything I can to just not take the jar and funnel them into my mouth. Yeah, I think if we're looking at blood sugar, blood glucose and insulin. And as long as we're talking about that, I did use a level food intake and quality amount and maybe timing is both tracker and. Yeah, full disclosure, they're a sponsor of the podcast regularly and I learned a ton. I'll tell you what I learned. I learned that indeed, my blood sugar goes up after I eat as well. Speaking of timing, what are your thoughts on fasting? And then, of course, movement and exercise.

The way I conceptualize the idea of fasting, obviously this is one where we need more words, right? Because the word fasting is so limited. There's so many different parts of this.

But skipping breakfast for me would be that or skipping dinner. That certain foods, although the foods that did this surprised me, certain foods tend to spike my blood sugar quite a bit. Grapes. That shouldn't be surprising. Food order was very powerful for me. I know that the data on food order are a little bit mixed and it's controversial. Sometimes I'll skip dinner, sometimes I'll skip breakfast.

Right.

But I like to eat like the French. I like some soup, then I like my entree. I like the salad at the end that turned out to have the steadiest and lowest rise in blood glucose for me. And then across time I also found that I love hot sauna. I go so hot with the sauna that I've been accused by Rogan and other people I'm going to turn myself into a brisket.

I think that some of the most interesting data that I've seen seen has been about if we reasonably compress our eating into daytime hours during the heart of the diurnal cycle when we are supposed to be eating. So essentially matching our chronobiology with our.

But after the sauna, my blood sugar spikes, presumably because I'm a bit dehydrated and it's the concentration of blood glucose. Is that, is that possible? Does that make sense?

It does make sense, but also the heat can affect the accuracy of the sensor itself.

Ah, okay. So that could be it too. But yeah, basically what it allowed me to do is make a few adjustments in terms of foods that I eliminated.

Or our behavior, which, you know, we are diurnal organisms so we kind of need to respect that.

Like when we eat less of food, ordering within a meal. And I find that I'm very susceptible to, if I don't include enough fat, dietary fat in the meal, then my blood glucose spikes, even if it's just like tuna. Right. But by including olive oil and other things, it really blunts it. And of course here we're doing coral.

We do that and we compress it in a moderate way. Our metabolic health is better. And so some of the studies that have looked at this one that was interesting was, and I think very hopeful for people is that if you take.

All the food, all the anecdote. But for me, I felt far better when I included a bit more fat and when the food order was adjusted the way I mentioned before, always including a little bit of fiber really helped. And that makes sense, right? Slow the absorption of the food, presumably. So I found that it was a very valuable experiment for me. Again, this isn't an advertisement.

It just so happens calories that you're going to eat and eat them in a six hour window.

I did this and really benefited from it. What are some other things that one can learn from continuous monitoring of blood glucose? What are some things to watch for that might signal a problem? And what are some fun things that one could do to explore and experiment? Because I like to explore and experiment.

Yeah, well, I mean a lot of the things that you just naturally learned are the things that have been shown in data versus a 12 hour window, totally same amount of calories, exact same food. This is a controlled experiment. Experiment. People who eat the same amount of calories in a six hour period are going to have much lower, statistically significant. Like you said, some of this data, it's like small studies, small groups of people. But for instance, adding fat and fiber to meals has a significant and repeatable impact in populations on lowering glucose response fat, probably in some part due to slowing gastric emptying and actually slowing the digestion process. So the rise in the blood sugar stream is going to slow down and then fiber. Both for that reason, but also because fiber can in a sense create like a mesh sort of blocking the absorption of some of the glucose that's in the meal. So literally kind of actually preventing you from absorbing all of the carbs. And we've actually lower glucose, 24 hour glucose and insulin levels compared to people who just space it out over the course of a 12 hour period. And it makes sense because if you're spacing that food out over the course of 12 hours, that is a different biochemical milieu in your body throughout the day. It's kind of similar to the walking. You know, it's like you are then stimulating insulin several more times. You are exposing the bloodstream to insulin and glucose just more throughout the day and giving the bloodstream less of an opportunity to sort of be clear from that glucose and that insulin and so, so compressing our eating. Actually seen that in the levels data set that the more fiber people include with their meals, we see essentially a direct relationship with lowering of their glucose excursions, which is really exciting because fiber is something that you can add to meals very easily. I put basil seeds, chia seeds, hemp seeds, flax seeds on a lot of my food at this point because it's essentially a little bit of fat. A window seems to be helpful for metabolic health and it's a bang for your buck, right? Like you can eat the same amount of food, you just have to eat in a shorter period of time. So for people who want to eat, you know, a lot, maybe just consider compressing it into daytime hours, six to eight hour window.

Yeah, for me, six is tough.

Six is tough.

The one meal per day thing is tough. I have friends like Lex Friedman that do the one meal per day thing. I end up eating so much food.

At that meal, a lot of fiber and it's kind of just helps you kind of get more from your, from your meal, so what you can learn. So I think step one, the way I think About a glucose monitor. First of all, I'll say the purpose of the glucose monitor is experience a.

Lot of kind of like mechanical distress as typically later in the day. I think an 8 to 10 hour window has worked well.

It's not to have to game the system and get flat glucose.

The purpose of for me most days I know as soon as we talk about intermittent fasting which is what or time restricted feeding, same thing, which is what we're talking about right now. I'm sure somebody's going to call up the there's been a study that's been circulating about a massive increase in cardiovascular risk in people doing intermittent fasting, in particular the sick.

The glucose monitor is curiosity. It's to start to understand how it's essentially an MRI for how all of our different dietary and lifestyle strategies are creating this readout of glucose in our body which I think can be really interesting. And in a world where so many.

Cards are six hour eating window. I just want to point out worst.

Study stacked against us with diet and lifestyle and where there's a lot of confusion about what's right for us. That can be like very helpful.

And actually as far as I know I could be wrong. But as far as I know that study is still in abstract form, it's not yet peer reviewed. Yeah, it's like the fact that studies that haven't been peer reviewed aren't even close to being peer reviewed are being like put out there as news stories is really problematic because I can tell you, as somebody who sat on the editorial boards of many journals for many years, I still sit on a few reviewed countless papers I've submitted and had to deal with reviews on countless papers.

Reducing the confusion and the cognitive load of our choices.

We know that the fact of the matter is like until the reviews are done, the revisions are made like that paper may never.

Keeping your blood sugar through the course of a lifetime in a low and healthy range. So I don't mean up and down spikes during the day, but keeping your blood sugar healthy throughout the course of your lifetime is probably the best thing we can do for longevity. Staying insulin sensitive.

See the light of day and it may end up in a journal that you is barely worthy of a place mat. It might end up in a high tier, high quality journal, but it might not. So just because there was, quote unquote, a study done means very little, but it means especially little, maybe nothing until it's peer reviewed.

Absolutely. And the methods were very poor in that study. It was a recall based study. I Think for two days, staying out of the diabetic range. And so one thing that the glucose monitor does for us is just give us more awareness and agency into days of recall of people's diet, like what the trends of our glucose are over time as opposed to a literally one data point snapshot once a year, which is notoriously very bad in terms of accuracy. So yeah, and I think I'm not in any way suggesting that a six hour window is the optimal window. I'm just sharing the data that suggests that compressing the window seems to have a favorable effect and I certainly don't do six hours. But I think when you look at what the average American is in the doctor's office, which is what the majority of us are used to doing, which is the average American has 11 eating events per day and 50% of Americans eat over a 15 hour window per day. I really love the idea that people who are able to wear glucose monitors every now and again, maybe once a year, maybe more than once a year, they know what I can recall those because I remember when I was writing the book I was like, that's a long time fifth their glucose is. And so they're never gonna walk into a doctor's office and have a bomb dropped on them about teen hours and eleven events. And, and every time you're doing that, you're going to be stimulating this glucose rise in the bloodstream exploits, exposing the blood vessels to that glucose. You're going to be turning on all the pathways with insulin to basically store it or you know, and it's so it's, it's strain for the body. And so I think giving the body time to intentionally to pre diabetes or type 2 diabetes, because you have the data, which is ultimately I hope the world that we can move towards for a lot of biomarkers. So you can see trends over time, which I think is very valuable. One thing that's fascinating in terms of early prediction of metabolic disease is that you can see you allow insulin to come down and to allow glucose to come down. What that does is it generates its metabolic flexibility. It gives our body an opportunity to have space to use accessible glucose and then convert into using stored fat. But be, and that ultimately is metabolic flexibility, the ability for the body giving the body opportunities to use glucose but then have time, how long it takes your glucose to come down after a meal. So in a normal, healthy insulin sensitive body, even if the glucose goes way up, it should come way down very quickly because the insulin is binding to insulin receptors and the Glucose is getting taken up and it'll lower what is.

Quickly over the course it should be.

Down and when there's not high glucose and insulin around to actually get into the fat stores and I think by two hours. But from what I've actually seen in our like most insulin sensitive people and also in one of the reasons why we have such a massive overweight and obesity, you know, rates in the country is because with the way the culture of eating right now, 11 eating events per day, eating over the course of 15 hours per day, I would imagine the average American body is rarely if ever tapping into their fat stores for energy in a meaningful way because we always have glucose available. Research that looks at young healthy populations, you should basically be spikeable to the body. If you think about again the stats about ultra processed food, about 70 coming down spike about 45 minutes and come down hour and a half, 90 minutes to two hours. But if percent of the items on the shelves in the grocery store ultra processed food and those ultra processed foods.

Are built on this is after. Sorry after last bite.

After last bite. Although it's hard to kind of exactly know. But yeah, meal is over I would say about 45 minutes to go up to the peak and then start coming down very quickly. Now if you refined added sugars and refined added grains. So we're just, we very rarely give the body the opportunity to rest and move into fat burning and that's where compressing the eating window can be valuable. Obviously people have talked, start to see that glucose is going up and then trailing very slowly back down to normal, maybe taking more than two hours, three hours. That is going to be. We talked about this before but, but fasting can be a stressor for the body, especially if your body's not used to using fat for energy. And so it's something to ease into and go slow. But I think if you're slowing down enough to really hear what your body's signal are saying, you can kind of know whether I think your fasting is working for you. One of those early indicators of potential insulin resistance, your body's not clearing the glucose. But that's not a metric that we use instant or not. I can tell if I've got too many other things going on. I haven't slept well, a lot of stress or practice at all. And I've actually seen myself very insulin sensitive. My insulin is like 2.5. And you know, if I don't I can tell that fasting is kind of making me jittery and not feel good versus If I'm really, if I have good capacity, I can feel that it's actually making me feel really incredible. And so tune in with your body obviously and you know, you can check your biomarkers. If you have a CGM on, you can see what's happening to your glucose. If you have a ketone monitor, you can see what's happening to your ketones and really actually track which I think makes fasting actually even, even more fun. And I am stressed and I have been sitting. My glucose will take way longer to come down. I have become transiently insulin resistant. So I think that's mention one other piece of data that I think is actually really kind of fun as well with timing of eating. There was a study that looked at people who ate the exact same meal at 9:30am or 8:30pm so basically after dark, essentially in the part of the diurnal phase. And we probably fascinating to see that. So looking what that ultimately the metric that we call that is area under the curve. You want a low area under the curve AUC, you shouldn't be eating versus early in the morning, 9:30. Um, and the glucose and insulin responses for the same meal at 8:30pm were significantly higher than when eating at 9:30am and so again, bang for your buck. It appears that eating after a glucose spike, so you want to spike and come down quickly, that's going to be. If you shade the area under the curve, it's a small amount. If you go up and then trail off for two to three hours in that earlier part of the day when we're active and our chronobiology is set up for metabolism and activity, we have a lower glucose and insulin response. There's also some evidence that melatonin hours, that's gonna be a lot of shading under that curve. And high AUC is associated with insulin resistance. Basically another which is secreted, you know, as we get closer to sleep, has somewhat of an effect on impairing our insulin sensitivity transiently. And so we may actually just be not absorbing the glucose from those meals effectively later at night. So I tend to kind of move a little bit more. Thing that you can see is essentially glycemic variability and glycemic variability, GV is a metric of how spiky. A little bit more low carb I would say throughout the day based on that data and what I've seen on my continuous glucose monitor. Basically just higher spikes for the same meal later in the day. So. So why not just kind of move it up earlier?

Very Interesting. Something I'll definitely try. I tend to push my carbohydrates to a little bit later.

Your curves are fasting paper out of Michael Schneider's lab at Stanford in 2018.

Called glucotype in the day for sake of sleep. Unless of course, I've done resistance training, which I do three times, I aim to do three times a week. And post resistance training I try reveal.

New patterns of glucose dysregulation. Totally landmark study. But basically they put continuous glucose monitors on non diabetic individuals who by standard criteria of diabetes do not get some.

Starchy carbohydrate in me just to replenish glycogen. And that then tends to reduce my carbohydrate craving later in the day. I love bread and butter, bread and olive oil pastas. And the other day I found this Argentine place and I love the steaks there. But they had gnocchi that it took everything I had.

Not have diabetes. And he showed that on a cgm, a continuous glucose monitor, you have these low variability people that are pretty much flat throughout the day with little every.

Neural circuit that releases GABA inhibition to my brain. To not order three of those orders, it was so good.

But you can walk after the gnocchi.

Oh, yeah, sure. I'll allow myself to do those things. I'm not super restricted, but again, I tend to eat high quality foods. By the way, these blueberries are amazing. Then you figure out where you got those because they're just tangy enough. I'm doing everything I can to just.

Teeny little teeny rolling hills after their meals. You have moderately spiky people and then you have very spiky people who are going up, down, up, down, up, down, up, down. When you correlate, just not take the.

Jar and funnel them into my mouth.

Correlate those different patterns of glycemic variability in non diabetic people. You find that the, the spikier they are, the worse their biomarkers are metabolically across the board. Insulin.

Yeah, I think if we're looking at blood sugar, blood glucose and insulin. And as long as we're talking about that, I did use a levels tracker. And yeah, full disclosure, they're a sponsor of the podcast regularly and I learned a ton. I'll tell you what I learned. I learned that indeed my blood sugar.

Goes up after I eat triglycerides, et cetera. So basically they're showing signs through variability of underlying dysfunction that you would never know from a standard test. Those are the people who I imagine.

Are probably gonna go that certain foods. Although the foods that did this surprised me.

Certain foods want to develop diseases and yet based on standard criteria, their doctors telling them that they're fine, that they're.

All the foods tend to spike my blood sugar quite a bit. Grapes. That shouldn't be surprising.

Same. So he also showed in that study that not.

Foods, food order was very powerful for me. I know that the data on food order are a little bit mixed and it's controversial, but I like to eat like the French. I like some soup, then I like my entree. I like the salad at the end.

That turned out to undiabetic individuals. When you have a CGM on are going into the diabetic range and the.

Steadiest and lowest rise in blood glucose.

For me and then pre diabetic range range a fairly significant amount. And we would never know that if.

You weren't across time. I also found that I love hot sauna. I go so hot with the sauna that I've been accused by Rogan and other people I'm gonna turn myself into a brisket.

If you weren't actually tracking like a movie of the glucose. So that's so glycemic variability, area under the curve. Those are two things. Another really interesting thing you can know from a CGM is dawn effect. So Don.

But after the sauna my blood sugar spikes, presumably because I'm a bit dehydrated and it's the concentration of blood glucose. Is that. Is that possible? Does that make sense?

It does make sense, but also the heat can affect the accuracy of the sensor itself. On effect is basically a term in the literature for how high your glucose rises.

Ah, okay. So that could be it too. But yeah, basically what it allowed me to do is make a few adjustments in terms of foods that I eliminated.

Or right when you wake up in the morning. I don't know if you noticed this when you were wearing a cgm, but some people notice that the second they.

Wake up, they're eat less of food ordering within a meal, glucose jumps up.

5, 10, 20, 30 points. What's happening here is that the cortisol awakening response to actually get you to wake up and get out of bed. That cortisol can.

And I find that I'm very susceptible to. If I don't include enough fat, dietary fat in the meal, then my blood glucose spikes. Even if it's just like tuna. Right. But by including olive oil and other things, it really blunts it. And of course here we're doing cor.

Cause you to dump a bunch of glucose from your liver because it's a.

Little bit of anecdote.

But for me I felt saying stress hormone cortisol. We gotta get up. We need glucose to fuel the muscles. Let's dump a little glucose. So it's normal. But what the research shows is that magnet far better.

When I included a bit more fat and when the food order was adjusted the way I mentioned before, always including a little bit of fiber really helped.

And that makes the intuitive dawn effect is correlated with insulin resistance. So the more the.

That's right. Slow the absorption of of the food presumably. So I found that it was a very valuable experiment for me. Again this isn't an advertisement.

It just so happens on effect you're getting. I think it can signal maybe the more stress you're under, the more cortisol you have floating around.

How I did this and really benefit from it. What are some other things that one can learn from continuous monitoring of blood glucose? What are some things to watch for that might signal a problem and what.

Are some fun big your cortisol awakening responses. But also if you imagine if you're dumping all that glucose from your liver and your cells aren't taking it up.

Well, because some things that one could do to explore and experiment. Because I like to explore and experiment.

Yeah you're insulin resistant. That that response that dawn effect is going to be higher. So I don't have the numbers right in front of me but typically I would want to see a dawn effect I think of like less than 10. Well I mean a lot of the things that you just naturally learned are the things that have been shown in data. And like you said, some of this data it's like small studies, small groups of people. But for instance adding fat and fiber to meals has a significant and repeatable impact in populations points. So you wake up and you may very well see a rise on lowering glucose response fat probably in some part due to slowing gases absence of any food yet. And you do not want to see that going strict emptying and actually slowing the digestion process. So the rise in the the bloodstream is going to slow down and then fight up 20, 30, 40 points. Some people see a little bump again with caffeine in the morning because it's more cortisol. And so that's fiber both for that reason but also because fiber can in a sense create like a mesh sort of blocking the absorption of some of the glucose that's in the meal. So literally kind of actually preventing you from absorbing all of the carbs. And we've actually seen that in the levels data set that the more fiber people include with their meals. Another thing that standard stuff would never tell you. So those are kind of some of the looking at early predictors of metabolic dysfunction. More of the fun stuff is like actually just figuring out like see essentially a direct relationship with lowering of their glucose excursions which is really exciting because fiber is something that you can add to meals very easily. I put basil seed. How is food affecting your body? And this is where people really enjoy it and like figure out like oh my God, this food that I thought was healthy is actually not serving chia seeds, hemp seeds, flax seeds on a lot of my food at this point because it's essentially a little bit of fat, a lot of fiber and it's kind of just helps you kind of get more from your meal. So what you can learn. So I think step one, the way I think about a glucose monitor, first of all I'll say the purpose of the glucose monitor is me and actually a lot of people I think who are trying to make healthy choices. My boyfriend like he, when we started dating, he started using levels, his healthy snack. He worked not to have to game the system and get flat glucose. The purpose of in Venice would be to go to Moon Juice and get oh gosh, I don't want to throw Moon Juice under the bus here but.

But he would have some tasty stuff they do.

The glucose monitor is curiosity. It's to start to understand how essentially an mri. But he would get this green juice that was sweetened with dates and it was like $9. And this was like the high for how all of our different dietary and lifestyle strategies are creating this readout of glucose in our body which I think can be really interesting. And in a world where so many cards are healthy choice and he saw the second he put on levels that it was causing a, a huge spike like 50, 60, 70 stacked against us with diet and lifestyle and where there's a lot of confusion about what's right for us. That can be like very helpful in actually reducing the confusion and the cognitive load of our choices. We know that points. And then he was crashing and he was actually trying keeping your blood sugar through the course of a lifetime in a low and healthy range. So I don't mean up and down spikes during the day, but keeping your brain to make a good decision. So now he's. He swapped his snacks out for more like you know, grass fed cheese and some flax crackers. And maybe like a venison stick or something like grabbing go blood sugar healthy throughout the course of your lifetime is probably the best thing we can do for longevity. Staying insulin sensitive, staying out of the diabetic range. And so one thing that the glucose monitor does for us is just give us more awareness and agency into like what the trends of our glucose are, stuff that isn't spiking as glucose. But I think it can help people figure out like which foods are doing what I want them to do and which maybe aren't over time as opposed to a literally one data point snapshot once a year. And same thing happened for so many of our member in the doctor's office, which is what the majority of us are used to. Whereas with oatmeal, unfortunately oatmeal, instant oatmeal is one of the biggest spikers in our data set. But I really love the idea that people who are able to wear glucose monitors every now and again, maybe once a year, maybe more than once a year, they know what their glucose is and so they're never going to walk into a doctor's office and have a bomb dropped on them about pre diabetes or type 2 diabetes because you have the data which is breakfast. And a lot of people are making that choice because they think it's heart healthy and in many people it's actually causing a big glucose excursion and crash and then in some other people it's not. And so it's really helping with what are the sneaky spikers and then where's the biochemical Ultimately I hope the world that we can move towards for a lot of biomarkers so you can see trends over time, which I think is very valuable. One thing that's fascinating in terms of early prediction of metabolic disease is that you can see how long it takes your glucose to come down after a meal. So in a normal healthy insulin sensitive body, even if the glucose goes way up, it should come way down very quickly because the insulin is binding to insulin receptors and the glucose is getting taken up and it'll lower what is quickly over the course of it should be down individuality. And there was a phenomenal paper out of Israel from Cell about seven years ago called personalized nutrition by prediction of glycemic responses. It made big waves, but it basically showed that you and I could eat the same handful of blueberries and have totally different by two hours. But from what I've actually seen in our like most insulin sensitive people and also in research that looks at young healthy populations, you should Basically be spiking, coming down, spike about 45 minutes and come down hour and a half, 90 minutes to two hours.

But it's if this is after, sorry, after last bite, after last bite, although.

It'S hard to kind of exactly know, but yeah, meal is over, I would say about 45 minutes to go up to the peak and then start coming down very quickly. Now, if you start to see that glucose is going up and then trailing the glycemic responses. So the idea of glycemic index as like a certain amount of food with a certain amount of glucose causes a certain glucose rise, it kind of debunked that. And that matters because repeated sustained glycemic variability over time is not good for our health. We want to choose the foods or balance the foods that are going to keep us relatively more stable. Very slowly back down to normal, maybe taking more than two hours, three hours. That is going to be one of those early indicators of potential insulin resistance. Your body's not clearing the glucose. But that's not a metric that we use use in standard practice at all. And I've actually seen myself very insulin sensitive. My insulin is like 2.5. And you know, if I don't sleep and I am stressed and I have been sitting, my glucose will take way longer to come down. I have become transiently insulin resistant. So I think that's just fascinating to see that. So looking what that ultimately the metric that we call that is area under the curve. You want a low area under the curve AUC after a glucose spike. So you want to spike and come down quickly. That's going to be. If you shade the area under the curve, it's a small amount. If you go up and then trail off for two to three hours, that's going to be a lot of shading under that curve. And high AUC is associated with insulin resistance. Basically another thing that you can see is so that that's, that's very helpful just understanding your personal response to food. And then what are the lifestyle strategies you can use? Sleeping better, walking after meals, more resistance training, cold plunging, breath work that can actually serve to modulate the food environment to actually reduce the glucose spikes. And people find that essentially glycemic variability and glycemic variability GV is a metric of how spiky your curves are. Fascinating paper out of Michael Schneider's lab at Stanford in 2018 called glucotypes reveal new patterns of glucose dysregulation. Totally landmark study. But all of those things can positively impact glucose Spikes, especially the. Basically they put continuous glucose monitors on non diabetic individuals who by standard criteria of diabetes do not walks after the meals. But it's been fascinating to see a lot of women, especially like menopausal women in our community who find that their glucose patterns are getting worse because not have diabetes. And he showed that on a cgm, a continuous glucose model, estrogen's dropping and that's gonna, you know, really take a hit on it. You have these low variability people that are pretty much flat throughout the day with little teeny, little teeny rolling hills after their meals. You have moderately spiky people and then you have very spiky people who are going up, down, up, down, up, down, up, down. When you correlate those different patterns of glycemic variability in non diabetic people, you find that the spikier they are the worst. Insulin sensitivity, they start resistance training. Glucose comes kind of right back down. So because of the monitor, they can feel more confident in the intervention they've chose to do to help with metabolism that kind of creates a virtuitous cycle. So those are some of the big things.

Those are big.

Their biomarkers are metabolically across the board, insulin, triglycerides, et cetera. So basically they're showing signs through variability of underlying dysfunction that you would never know from a standard test. Those are the people who I imagine are probably gonna go on to develop diseases and yet based on standard criteria, their doctors telling them that they're fine, that they're all the same. So he also showed in that study that not. Can I mention one more? I know, I love that I just, I could obviously talk about this all day. I think it's fascinating. But this is just one more that I think is fascinating because this was a paper in Nature from last year that talked about. And this might actually be one of the most valuable things to people, which is that again, talking about cravings. Undiabetic individuals, when you have a CGM on are going into the diabetic range and the pre diabetic range a fairly significant amount. And we would never know that if you weren't, if you weren't actually tracking like a movie of the glucose. So that's so glycemic variability, area under the curve. Those are two things. Another really interesting thing you can know from a CGM is dawn effect. So dawn effect is basically a term in the literature for how high your glucose rises right when you wake up in the morning. I don't know if you noticed this when you were wearing a cgm. But, but some people notice that the second they wake up, they're. We all want to get off the craving grip. This paper in Nature showed that essentially when people spike their glucose with high carb, high starchy foods, they'll often have a big crack. Glucose jumps up 5, 10, 20, 30 points. What's happening here is that the cortisol awakens afterwards. And the reason for that is because a big spike leads to a lot of insulin secretion and then you soak up all the glucose and sometimes you can actually go back below your baseline. So a small spike response to actually get you to wake up and get out of bed. That cortisol can cause you to dump a bunch of glucose from your liver because it's basically saying stress hormone cortisol, we gotta get up, we need glucose to fuel the muscles, let's dump a little glucose. So it's normal. But what the research shows is that magnitude of dawn effect is correlated with, with insulin resistance. So the more the usually won't lead to a crash, but a big spike often will. That's called reactive hypoglycemia. Postprandial hypoglycemia. A lot of people think they're dealing with hypoglycemia, when in fact what they're really dealing with is that they're spiking their glucose too high and then they're crashing.

I see.

And dawn effect you're getting, I think it can signal maybe the more stress you're under, the more cortisol you have floating around, how big your cortisol awakening response is. But also if you imagine if you're dumping all that glucose from your liver and your cells aren't taking it up well because you're insulin resistant, that that response, that dawn effect is going to be higher. So I don't have the numbers right in front of me, but typically I would want to see a dawn effect, I think of like less than 10 points. So you wake up and you may very well see a rise. The paper showed that the extent of post meal diploma, the crash after the spike was predictive of 24 hour energy intake and cravings for carbohydrates. And there's absence of any food yet and you do not want to see that going up 20, 30, 40 points. Um, some people see a little bump again with caffeine in the morning. This makes sense. If you crash low, that is a signal to your body, we have to get our glucose back up and it, it will drive you to eat High energy foods because it's more cortisol. And so that's another thing that standard stuff would never tell you. So those are kind of some of the looking at early predictors of metabolic dysfunction. More of the fun stuff is like actually just figuring out like how is food affecting your body. And this is where people really carbohydrate rich foods and cravings. So one of the best things we can do, I believe from my personal experience, from members experience and with some data to support this is that one enjoy it and like figure out like, oh my God, this food that I thought was healthy is actually not, you know, serving. One of the adjuncts we can use to monitor our, to manage our cravings is actually to like lower the extent of our spikes so that we crash less. And so that was a fascinating study looking at CGM data. Me and actually a lot of people I think who are trying to make healthy choices. My boyfriend, like, like when we started dating, he started using levels. His healthy snack, he worked in Venice would be to go to Moon Juice and get, oh gosh, I don't want to throw Moon Juice under the bus here.

But he would get, they have some tasty stuff.

They do. But he would get this green juice that was sweetened with dates and it was like $9. And this was like that.

That's interesting. So the CGMs can reveal things not just in the immediate meal period, but can relate to sort of downstream consequences. Yeah, again I found it to be.

Healthy choice and he saw the second he put on levels that it was causing a huge spike, like 50, 60, 70.

Tremendously useful. I'm so glad you mentioned sleep by the way. I'm going to resist the temptation to rattle off 20 studies showing that. Oh God, you know, even having too much bright light in a room while one is sleeping at night, even dim light points.

And then he was crashing and he was actually trying to make a good decision. So now he's swapped his snacks out for more like grass fed cheese and some flax crackers and maybe like a venison stick or something like grab and go stuff that isn't spiking his glucose. But I think it can help people figure out which foods are doing what I want them to do and which maybe aren't, which is, you know, I.

Don'T want to scare people into thinking they have to sleep in complete darkness. Although an eye mask can be, can be great, can alter morning blood glucose levels in. I believe it was adults and kids as well. There's a study in Proceedings in the National Academy of Sciences. I have to go back and check if it included kids, but pretty striking. And then there's something very clear about.

The fact that and same thing happened for so many of our members with oatmeal. Unfortunately, oatmeal, instant oatmeal is one of the biggest spikers in our data set for breakfast. And a lot of people are making that choice because they think it's heart healthy. And in many people it's actually causing a big glucose excursion and crash. And then in some other people it's not. And so it's really helping with what are the sneaky spikers. And then where's the biochemical when people.

Get the early night sleep of four to five hours but then don't get the REM dominating last hour or two of sleep in the morning that that resting blood glucose is altered. It's so interesting to think about what's going on in sleep. There's at least one paper that I'm aware of where they had people breathing into a tube during sleep to measure what sorts of metabolism they were undergoing. And it's interesting during a full night's sleep individuality.

And there was a phenomenal paper out of Israel from Cell about seven years ago called Personalized nutrition by prediction of glycemic responses. It made big waves but it basically showed that you and I could eat the same handful of blueberries and have totally different glycemic responses. So the idea of glycemic index as like a certain amount of food.

All of us seem to transition between different forms of metabolism. I'll send you this paper, it's really cool and I'll put a link to it in the show. Note caption such that at one portion of the night we're metabolic rely more on, let's just call it sugars for a second.

Food with a certain amount of glucose causes a certain glucose rise. It kind of debunked that and that simplicity.

Other times we're more ketone dominant. There's market shifts in metabolism throughout the night. It's almost like the brain and body.

Matters because repeated sustained glycemic variability over time is not good for our health. We want to choose the foods or balance the foods that are going to keep us relatively more stable. So that's very helpful. Just understanding your personal response to food. And then what are the lifestyle strategies you can use? Sleeping better, walking after meals, more resistance training, cold plunging breath work that can actually serve to modulate the food environment to actually reduce the glucose spikes.

And people find that cycle through all the different modes of metabolism throughout the night. And then almost like a rehearsal of the metabolic pathways, if we can anthropomorphize a bit here. But then if sleep is truncated, it clearly has an effect on daytime fuel regulation. Just so interesting. So getting sufficient sleep, getting quality sleep.

Is all of those things can positively impact glucose spikes, especially the walks after the meals. But it's fascinating to see a lot of women, especially like menopausal women in our community who find that their glucose patterns are getting worse because estrogen's dropping. And that's gonna, you know, really take.

A hit on it is absolutely key. There's a lot for people to pay attention to, but you've given us a lot of tractable avenues for people to do that that are mostly behavioral. There's a few don'ts, but mostly some do's.

Insulin sensitivity, they start resistance training, glucose comes kind of right back down. So because of the monitor, they can feel more confident in the intervention they've chosen.

We haven't mentioned that you don't need to even perhaps belong to a gym. It's like. And with the cold exposure thing, I always say if anything, it'll save you money on the heating bills to do.

To help with metabolism. That kind of creates a virtuous cycle. So those are some of the big things.

Those are big.

Can I mention one more? I know, I love that I could obviously talk about this all day, I think it's fascinating. But this is just one more that I, I think is fascinating because this was a paper in Nature from last year.

There's a literally potential negative cost there.

That talked about. And this might actually be one of the most valuable things to people, which is that again, talking about cravings, I.

Think levels and other CGMs are really interesting and valuable to experiment with. What sorts of other stuff is going to soon be monitored in our blood? Because for instance, I would love to know continuous hormone levels, lipid levels, blood sugar levels. I mean, are we moving past just.

We all want to get off the craving grip. This paper in Nature showed that essentially when people spike their glucose with high carb, high starchy foods, they'll often have a big crash afterwards. And the reason for that is because a big spike leads to a lot of insulin secretion and then you soak up all the glucose and sometimes you can actually go below your base baseline. So a small spike blood glucose.

And are. Are there soon to be other things in these monitors so that when we. And by the way, if you haven't used this, it's really cool. You just take your phone, you scan it over the, the sensor and then it basically gives you a chart graph of what's going on in your bloodstream.

And now they're all, the latest gen of each of them are all Bluetooth now. So no more scanning, which is kind of nice. And that usually won't lead to a crash, but a big spike often will. That's called reactive hypoglycemia. Postprandial hypoglycemia. A lot of people think they're dealing with hypoglycemia when in fact what they're really dealing with is that they're spiking their glucose too high and then they're crashing.

I see.

And the answer is yes, there are several different analytes that we're going to be able to track. And the paper showed that the extent of post meal diploma the crash after the spike was. Abbott, which is one of the three main manufacturers of CGMs, has announced that they're, they have a new product called the Lingo which is going to actually be able to measure ketones, lactate and alcohol predictive of 24 hour energy intake and cravings for carbohydrates continuously. Which is pretty interesting from like a metabolic, comprehensive metabolic. This makes sense. Sense. If you crash low, that is a signal to your body. We have to get our glucose back up and it will drive you to eat high energy foods, carbohydrate rich foods and cravings. So one of the best things we can do, I believe from my personal experience, from members experience and with some data to support this, is that one of the adjuncts we can use to monitor our, to manage our cravings is actually to like standpoint, different, different sensors for each, not all in one. So I think we'll have to like polka dot ourselves if we're tracking all those things and then lower the extent of our spikes so that we crash less. And so that was a fascinating study looking at CGM data. Dexcom, which is the other main company that makes CGMs, has just announced that they're coming out with an over the counter, non prescription version of a CDM CGM called the Stella later this year. So there's exciting things happening in the industry that's interesting.

So the CGMs can reveal things not just in the immediate meal period, but can relate to sort of downstream consequences. Yeah, again I found it to be tremendously useful. I'm so glad you mentioned sleep by the way. I'M going to resist the temptation to rattle off 20 studies showing that. Oh God, you know, even having too much bright light in a room while one is sleeping at night, even dim.

Light SRI and I really do think continuous monitoring, it's gonna expand to a lot of these other things that you're talking about, hormones, et cetera. And I mean it really needs to. I think that, you know, snapshots of a dynamic system are just never gonna really be able to give us a full picture on what's going on.

And it's just, you know, I don't wanna scare people into thinking they have to sleep in complete darkness. Although an eye mask can be, can be great. Can alter morning blood glucose levels in I believe it was adults and kids as well. There's a study in Proceedings in the National Academy of Sciences. I have to go back and check if it included kids, but pretty striking. And then there's something very clear about the fact that when people get the early night sleep of four to five hours, but then don't get the REM dominating last hour or two of sleep in the morning, that resting blood glucose is altered. It's so interesting to think about what's going on in sleep. There's at least one paper that I'm aware of where they had people breathing into a tube during sleep.

What we really want to be able to do to dig our way out of this healthcare crisis, I think is empowerment individually and understanding how this rapidly changing environment is affecting our own biology so we can make the targeted choices.

To hopefully measure what sorts of metabolism they were undergoing. And it's interesting, during a full night's.

Sleep we change the environment to be more conducive to cellular health. And continuous monitoring is a closed loop biofeed.

All of us seem to transition between different forms of metabolism. I'll send you this paper, it's really cool. And I'll put a link to in the show note caption such that at one portion of the night we're relying more on, let's just call it sugars for sake of simplicity. Other times we're more ketone dominant. There's a market shifts in metabolism throughout the night. It's almost like the brain and body.

Back that can, that can help us with that decision making and essentially predict failure of the system rather than wait for failure of the system before we do something about it. So yeah, I think lots coming down the pipeline.

Love it.

Yeah.

Let's talk a little bit about mindset. This is a really interesting topic that you include in Your book. We've had guests come on and talk about growth, mindset strength, stress can be enhancing mindset. I'm big on mindset. Cycle through all the different modes of metabolism throughout the night and then almost like a rehearsal of the metabolic pathways. If we can anthropomorphize a bit here, but then if sleep is truncated, it clearly has an effect on daytime fuel regulation. Just so interesting. So getting sufficient sleep, getting quality sleep. Because I'm interested in how our cognitive reframing or cognitive framing can just change the way our biology works. And vice versa, of course. But you talk about mindset in a certain context and one of the favorite passages around that that I really enjoyed was the relationship between is absolutely key. There's a lot for people to pay attention to, but you've given us a lot of tractable avenues for people to do that that are mostly behavioral. There's a few don'ts, but mostly some do. Kind of like trying to come control everything and nature, you know, like and, and how getting. We haven't mentioned that, you know, you don't need to even perhaps belong to a gym. It's like. And with the cold exposure thing, I always say, you know, if anything it'll save you money on the heating bill. So there's a, there's a literally neg potential negative cost there. I think levels and other CGMs are really interesting and valuable to experiment with with what sorts of other stuff is going to soon be monitored in our blood? Because for instance, I would love to know continuous hormone to nature itself can be valuable for us. So maybe touch a little bit on mindset if you will and what are your thoughts on nature? Literally getting out of doors.

Yeah.

Levels, lipid levels, blood sugar levels. I mean are we moving past chest?

I think, I think that mindset and more broadly than mindset, I think psychology and our relationship specifically with fear and.

Control, I think glucose and are. Are there soon to be other things in these monitors. So that when we. And by the way, if you haven't used this, it's really cool. You just take your phone, you scan it over the, the sensor and then it basically gives you a chart graph of what's going on in your bloodstream.

And now they're all, all the latest gen of each of them are all Bluetooth now. So no more scanning which is kind of nice. And they're probably the most under recognized thing that is impacting the metabolic health crisis, the chronic disease epidemic. There has been data that's looked into this. We know that there's studies showing that loneliness impacts mitochondrial function and that loneliness is a risk factor and stress is a risk factor in these things. And something really fascinating actually with the CGM data, answer is yes, there are several different analytes that we're going to be able to track. And Abbott, which is one of the three main manufacturers of CGMs, has announced that they have a new product called the Lingo, which is going to actually be able to measure ketones, lactate and alcohol continuously. Which is pretty interesting from like a metabolic, comprehensive metabolic. Is that many people who wear a cgm, I don't know if you saw this but. But when you feel stressed it actually has a metabolic standpoint, different sensors for each, not all in one. So I think we'll have to like polka dot ourselves if we're tracking all those things. And then diabetogenic effect, it literally causes our blood sugar to go up when we feel stress. And that can be a fascinating unlock for people to realize. I kind of feel like Dexcom, which is the other main company that makes CGMs, has just announced they're coming out with an over the counter, non prescription version of a CGM called the Stella later this year. So there's exciting things happening in the industry. I'm okay right now, but my body is telling me something different. It's telling and I really do think continuous monitoring, it's going to expand to a lot of these other things that you're talking about telling me that biochemically I'm actually releasing energy stores from my liver, glucose, hormones, et cetera. And I mean it really needs to, I think that, you know, snapshots of dynamics to fight some threat that, you know, I wasn't. System are just never going to really be able to give us a full picture on what's going on and really aware of. So we definitely understand there's this link here, but it's certainly not made its way into clinical practice. So the way I think about it is that what we really want to be able to do, to dig our way out of this healthcare crisis, I think is, is empowerment individually and understanding how this rapidly changing environment is affecting our own biology. So we can make the targeted choices to hopefully change the environment to be more conducive to cellular health. And continuous monitoring is a closed loop biofeed. We know about the cells, and especially the mitochondria, is that the mitochondria are more than the powerhouses of the cell. They actually are a part of the cell that is constantly tracking resources and Threats and are basically modulating energy resources based on that. That can, that can help us with that decision making and essentially predict failure. And the threats can be anything. They can be a virus of the system rather than wait for failure of the system before we do something about it. So yeah, I think lots coming down the pipeline.

Love it.

Yeah.

Let's talk a little bit about mindset. This is a really interesting topic that you include in your book. We've had guests come on and talk about growth. Mindset, stress can be enhancing mindset. I'm big on mindset because I'm interested in how our cognitive reframing can be.

And this is all coordinated through this thing called the cell danger response. It can be a virus, it can be a toxin in the environment, it can be lack of micronutrients for the electron transport chain that it needs to do its function. It can also be psychological threat because of course our psychological milieu translates through nerve.

Cognitive framing can just change the way our biology works and vice versa, of course. But you talk about mindset in a certain context and one of the favorite passages around that that I really enjoyed was the relationship between kind of like trying to control everything and nature, you know, like and. And how getting into nature itself can be valuable for us. So maybe touch a little bit on mindset, if you will, and hormones and.

Neurotransmitters and our microbiome to affect our cellular biology throughout our whole body, our cell.

Yeah. What are your thoughts on nature literally getting out of doors?

Yeah. So I think, I think that mindset, and more broadly than mindset, I think psychologists here, every single thought that we're thinking through biochemistry and when a cell and a mitochondria are getting the message that there is a threat or g. And our relationship specifically with fear and control, I think they're probably the most under recognized thing that is impacting the metabolic health crisis, the chronic disease epidemic. There has been data that's looked into this. We know that there's studies showing that loneliness impacts mitochondrial function and that loneliness is something to be afraid of. They are going to change metabolic function towards defense alarm factor. And stress is a risk factor in these things. And something really fascinating actually with the CGM data, threat response and away from repair homeostasis building essentially thriving. And I think what's really maybe the most unnatural thing about our modern world, you know, the food of course is unnatural, 70% is that many people who wear a CGM. I don't know if you saw this, but when you feel stressed, it actually Has a diabetogenic effect. It literally causes our blood sugar to go up when we feel stress. And that can be a fascinating unlock for people to realize. I kind of feel like I'm okay right now, but my body is telling me something different. It's telling sun is ultra processed. But we also have this device in our hands literally that biochemically I'm actually releasing energy stores from my liver glucose to fight some threat that, you know, I wasn't with us all the time streaming fear inducing media really aware of. So there's, there's, we definitely understand there's this link here. But into our brains and eyeballs every waking moment of the day if we let it. So we're glued to our screens and our devices and right now. But it's certainly not made its way into clinical practice. So the way I think about it is that what we know about the cells and especially the mitochondria is that the mitochondria are more than the powerhouses of the cell. They actually are a part of the cell that is constantly tracking how essentially the traumas and fears of 8 billion people all over an entire globe are now hours to process resources and threats and are basically modulating energy resources based on that. And the threats can be anything. They can be a virus. And our cells and our mitochondria, there is no escaping it. They are going to respond to that. And so I think a big part of the metabolic health conversation is how do we create a sense can be. And this is all coordinated through this thing called the cell danger response. It can be a virus, it can be a toxin in the environment, it can be lack of micronutrients for the electron transport chain that it needs to do its function. It can also be psychological threats because of course our psychological milieu translates through nerves and hormones and neurotransmitters and our microbiome to affect our cellular biology throughout our whole body. Our cells of safety in our bodies, no matter what is happening outside of our bodies. And this can come down to every person's journey will be different for this. Because let's hear every single thought that we're thinking through biochemistry. And when a cell and a mitochondria, things that cause a sense of threat or fear for any two people are going to be different. And I think some of the main categories is one unresolved childhood trauma like are getting the message that there is a threat or something to be afraid of. They are going to change metabolic function towards defense alarm thing that I think is getting a Lot more talked about these days, threat response and away from repair, homeostasis building, essentially thriving. So and I think what's really maybe the most unnatural thing about our modern world, you know, the food of course is unnatural 70%. But like what's embedded in our nervous system, these limiting beliefs and memories that are really wired, that create a sense of percent is ultra processed. But we also have this device in our hands literally hyper vigilance in us sort of all the time. What's coming in through our devices, our phones, our computers, the media that we're exposed to that's constantly giving a fear signal. And I think on a broader level with us all the time streaming fear inducing media into our brains and eyeballs every waking moment of the day, if we let it. So we're glued to our screens and our devices. And right now, big western one that we don't talk about is now essentially the traumas and fears of 8 billion people all over an entire globe are now all hours to process literally like existential fear of mortality. We have a very deep spiritual and our cells and our mitochondria, there is no escaping it. They are going to realized very uniquely death fearing culture, like you look at other cultures, Eastern indigenous, the Stoics, they all had intense curiosity about death respond to that. And so I think a big part of the metabolic health conversation is how do we create a sense of safety in our bodies no matter what is happening outside of our bodies. We talk about the cycles of life, there's this real engagement with it that we are so afraid of. And this can come down to every person's journey will be different for this. Because in the western system, to the extent that our entire healthcare system act, things that cause a sense of, of threat or fear for any two people are going to be different. And I think some of the main categories is one unresolved childhood trauma. Like something that I think is getting a lot more talked about these days. I think, you know, we've built it around like we're not going to, we're, we're not going to help you thrive, we're just going to do whatever we can to make sure you don't die. Like that's, it's built in every is but like what's embedded in our nervous system, these, these limiting beliefs and memories that are really wired that create a sense of hyper vigilance in us sort of all the time. What's coming in through our devices, our phones, our computers, the media that we're aware and so we've got the devices, we've got the childhood trauma, we've got the fear of mortality we're exposed to that's constantly giving a fear signal. And I think on a broader level, a big Western one that we don't talk about is literally, we have a very poor system of mental health care in the culture. And I think that through all these things, Americans are getting literally like existential fear of mortality. We have a very deep spiritual crushed mindset in psychology wise. And that is a big, big trigger of our mitochondrialized, very uniquely death fearing culture. Like you look at other cultures, Eastern, indigenous.