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

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 ourselves. 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 foods 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 ourselves, can combine to create conditions of obesity, as well as ways that we can manage those things, or even reverse 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 embody 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've 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 the general public. And keeping with that theme, I'd like to thank the sponsors of today's podcast. Our first sponsor is Maui Newi Venison. Maui Newi Venison is the most nutrient dense and delicious red meat available.

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That's Aeropress.com slash Huberman. And now for my discussion with Dr. Casey Means. Dr. Casey Means, welcome. Dr. Andy 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 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 nine 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 so when you're bubbling up of all of those chemical reactions is our lives.

And so when metabolism is not working properly, it's essentially creating under powered cells. And like any city or factory or machine, not having adequate power will lead to dysfunction.

And the metabolic spectrum of diseases so vast is because we have over 200 cell types in the body. And under powering in different cell types is going to look like different symptoms because under powering in an astro site is going to look different than under powering in ovarian thicacel or an endothelial cell.

And 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. And so we have a lot of 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 them all with them. And really ignoring that underlying foundational root cause of metabolic function. And passing 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 were actually getting so the more we do technological innovation in all these different specialties, the sicker were getting and I think what the real nugget there that everyone really 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 were 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 over say 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 and 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 in 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 on the line, engines working well, transmission isn't working as a bunch of issues and no factory, no car manufacturer would tolerate that nor with 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 and developed the system.

They provide an opportunity to go and fix the problems or trying to millerate the problems, but really what we need to do to make this analogy much prefer than otherwise would be 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 becoming deficient in this, 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 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 and 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 or 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

and 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.

In nature has changed. We actually are indoors as Americans 93% of a 24 hour periods that totally change their relationship with light. We have 80,000 synthetic toxins in our food, water, air, personal care products, home care products. We live a thermonutral existence now with our thermostat. 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.04% of human history that we've even had artificial light.

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 devoid 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 an obesity and overweight epidemic that's affecting close to 80% of American.

So while 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 these 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 as 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 an 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 build up.

But we confuse the pus build up with the disease which is actually happening inside the cells and so you start looking at PubMed as a 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 and a lot of these cell types.

And then what does that do in this case 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 extra cellular 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 pure genic neurotransmitter that massively activates the immune system to come and help. So 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 lacing 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 by products 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 path of physiology of arthritis.

What's the pathophysiology of Alzheimer's dementia. What's the pathophysiology of type 2 diabetes obesity, fatty liver disease, polyester covariance and 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 health care surround since 90% of health care costs go towards treating the downstream symptoms of these and for every marginal dollar we're spending on treating symptoms we're getting 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.

Mido-condrial 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 like 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 a lot of

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 there I appreciate the analogy to living in California I've lived here my entire life I have been outside of California but I'm 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 on the body so

in any case not to be too dark and pessimistic well that's the health care cost I'm in 10 great hope and still a lot of love for California you know it's pretty great it's got it's 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 the same issues with

metabolic dysfunction occurring outside of the United States I would imagine so yeah any country where we've exported the standard American diet and some of the other norms of western living or sorry to see the same rates of of chronic disease but like it is worth not missing words here of 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 then the second highest spending country in the world so we are we are objectively failing and that failure is predicated in our cult of siloing conditions 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 specialist 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 all timers is going up fat delivered disease the 15 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 but 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 in ENT your 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 belly wick so before we pivot to solutions yeah 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 yeah 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 there are shorts there 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 fats of the pain is fat etc 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 or 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 can be toxic fats like ceramides and diacyl glycerol

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 the body says okay we're going to block the ability of the insulin receptor to transduce its intercellular 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 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 it's really that simple and the beauty is we can do all of those things if you actually break down like what it what those three things mean it means promoting mytoffogy 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 H 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 mytoffogy

you know we can focus on various types of like endurance exercise and high intensity interval exercise there's compounds like ural ethena that promote mytoffogy when we talk about improving our you know oxidative 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 7000 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 mytoffogy 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 your improving the cells capacity to do that conversion process better I'd like to take a brief break and acknowledge our sponsor AG one by now most of you have heard me tell my story about how I've been taking AG one once or twice a day every day since 2012 and indeed that's true

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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 we'll get into but since we touch on lifestyle and because we've been talking about this 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 don't 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, my topology, the removal of dead or dysfunctional mitochondria

so they can be replaced. So about the walking one first. 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 like 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 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 cos 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 cos 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 low grade way like walking or doing a couple of air squats, 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 constitutally 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 to that I think are fascinating where they basically took two groups and they said, okay, we're going to 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.

Three separate groups, either 20 minutes before either 20 minutes after or two to three minutes every 30 minutes, okay, 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.

So 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 in the research mechanistically is shown that it's because we're consistently putting this these channels of the membrane to take up the substrate, use the substrate. This is not in 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 as 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.

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 was doing resistance train, which I think is terrific used to be such, you know, so restricted to niche sub culture 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.

It like to study the history of exercise culture and it wasn't, but in the 60s when 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 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, involves, excuse me, and 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 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 the water.

And you're taking up 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 of its 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 their 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 their beautiful data there in my opinion.

Okay, so 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 modern strung your 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 3000 to 4000 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, you know, get the get the heart rate up moderate level.

So for 150 minutes a week or strenuous for 75 minutes a week, those are going together to be potent stimuli for biogenesis, mytoffogy, mitochondrial fusion for increasing antioxidant enzymes that are going to protect the mitochondria from that oxy of stress.

And the one that's just actually not in there in the sort of the basic recommendations for Americans is the walking and I would just absolutely add to that at least 7000 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 is just a few minutes a day. So that right there are going to be like a big multifaceted set of signals for increasing mytochondrial capacity in different ways.

Terrific. What are your thoughts on under the desk treadmill? I don't own one of these, but and I try and get walks and I definitely do my three resistance training exercises 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 hardest going to jump out of my chest and I'm going to get going to die from gas me there, but luckily that's why I haven't died nonetheless.

The total time commitment isn't that great, but I find it 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 desk 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 radically change the health United States with real physiology underneath it so there's actually been research on under desk standing desk 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 two and a half hours per day during the work day so not a lot at very so 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 to 66 pounds assuming it's

linear progress 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 forgot and I'm even on it. Is that right so you're able to work without thinking about having to to 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 glacial slow I do put my or a 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 step because the or rings measuring hand or

accelerometer yeah but it it's incredible how even at a 1.0 1 mile per hour speed after two to three hours you're easily going to get six seven eight thousand 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 it's just a great way to build back in what

modernity took away and that unfortunately is unavoidable that 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 a have an impact on body composition which I think is is a great easy inexpensive thing for people to do but if you if you don't want to buy one like just set those timers and and build in the walks you know throughout the day outside

terrific yeah I'm a I'm a fan of getting walks when I can I also I wonder your thoughts on there was a study not sure if you're familiar with it published out the University of Houston where they looked at what they called it soleus push ups which all the gym goers are going to roll their eyes

imagine sitting down and raise pressing your toe against the ground and raising your heel so kind of like seated calf raise but no way 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 a tax that I got like people really didn't like the idea that this was any different

so-called neat non-exercise and 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 condition so it's trying to 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

and so the 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 it's medicine

and I find the concept of neat just endlessly fascinating you know because we kind of come up with this term non-exercise activity thermogenesis and the data is really good about it like it's basically shows that this is a prime potential intervention for the obesity epidemic and it all goes back to the cell like it's it's essentially a stimulus that's telling the body to 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 numbers 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 super markets 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 every day 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 think 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 the the 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 my new show 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 health care 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 and

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 that might occur to you they possibly impact oxy stress they possibly impact inflammation so yeah I love it I love simple solutions that hit multiple seller pathways that can make everybody healthier I'd like to just take a quick break

and acknowledge one of our sponsors inside tracker inside tracker 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 media 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 inside tracker 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 inside tracker also offers inside tracker pro which enables coaches and health

professionals to provide premium and personalized services by leveraging inside trackers analysis and recommendations with their clients if you'd like to try inside tracker you can go to inside tracker and you get 20% off any of inside trackers plans again that's inside tracker dot com slash human 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 read a little bit about it was really hard to access

actually went to the student health center and said you know can I just get like 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 you know what why would you do that now it's very easy to find places that will do blood test 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 what do you think are the three to five things that basically everybody if they can should know about what

circulating in their blood I'm imagining LDL HDL this kind of thing I guess APOB is a big favorite of our friend Peter Tia 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 my point here's not to answer the question 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

a number to them because obviously there's a lot of debate about like what's everyone's favorite lab tests but I think about it is 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

waste 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 in what it what it corresponds to yes great thing and I will say first of all the reason I'm choosing these it's not 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 metabolit dysfunction use those biomarkers so I think because I'm not sure if you're going to be able to do that.

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 are have suboptimal

metabolism and then follow up study from the journal of the American College of cardiology from last year so 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 a 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 are the doctors often if they see all these lab tests it'll be an electronic health record we've all been through this

experience experience they'll come up on the screen and there'll 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 you know your LDL's high we need to bring it down oh your glucose is high we need to bring down all your blood pressure is high we need to bring it down but when 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 he will go back and see less than 5.7% total cholesterol to HDL ratio less than 3.5 to 1

waste or conference less than 35 inches through in or 40 inches for men and blood pressure less than 120 over 80 if those things were in those ranges and you were not medication for blood sugar or blood pressure or whatnot you were considered optimally metabolic 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 human globin a one C is I think most people are familiar with HDL cholesterol being the quote unquote good cholesterol and LDL being the bad cholesterol as I say that I know I'm going to get dog pile yeah totally yeah 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 yeah so just as a yeah to stay functional here what will frame it that way for now with with the caveat that that might not be the whole story right isn't the whole story

that I'm triglycerides fat in the blood fatty stuff but so key to understand about the triglycerides it's not people 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 I know you and you and Rob Lustig talked about this at length but I'm and laying in lane yeah I mean one of the things that's really tricky gosh is that the language around

nutrition and health is complicated because people hear the word fat they think body fat right but then they also think the macronutrient fat yes 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

complicates and so there's a middle ground right there's a 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 right in order to explain 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 might get 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 blood stream 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 blood stream okay well where's all that this the body does not want lots of glucose floating around in the blood stream because it can literally independently cause and

the whole thing is because endothelial dysfunction which is basically blood vessel problems it can cause oxidative stress in the blood stream it can cause glycation which is sugar literally just sticking to things we the body doesn't want that glucose high in the blood stream so it converts it to triglycerides to be stored in a storage form of energy

and the 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 over nutrition

too much substrate not enough processing glucose is going to go up triglycerides are going to go up and so again 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 they're fasting glucose is 99 one point 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 is someone thinking about the mitochondria is like this person is definitely metabolically dysfunctional they're on the highest end of normal for both triglycerides in glucose there's something there's 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 cells processing through energy great and things are moving through and we're not backing up in the blood stream we're not converting to triglycerides so that's where really optimal ranges get in 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

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 blood stream

and then just talking about one other biomarker and 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 you know in the mitochondria and whatnot and a really 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 is insulin resistance the body is going to turn out more insulin to try and overcome the insulin block to drive the sugar into the cells so insulin levels rise while 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's sort of comes across to many people as old school right but when a T.O. was here one of the several times he was here he he really pushed on blood pressure is just such a key metric I mean obviously if blood pressure is high you're getting less nitric oxide through 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 build up of metabolic waste

all this stuff and now we can start to see the picture yeah it's trying 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 is your physician what's the secret code

I'll give away one that 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 going to come after me now with I guess with deathoscopes

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 let you know 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 like something's changing and the patient saying something's changing actually would be irresponsible of them to not give the blood test so there you go bring it on M.D.s. yeah truly and I think the nice thing about these again very basic tests and there are so many other tests that I talked about in my book and that you've talked about on your podcast apob uric acid fasting insulin home I.R.H.S.C.R.P

liver function test ggt all these other tests that are great that can really tell us more about mitochondria function 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 the the

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

they're creeping up or if many of them are a little bit high like we need to focus 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 going to get pushback often if you ask her fasting insulin I would say probably I mean even though doctors are waking up a little bit like maybe 85% of people are going to 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 a 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 crum 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 hit or zone two 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 re re test in a few months and see if you're moving in the right direction you don't you don't have to trust your doctor you don't

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 range they just mentioned are not optimal like we you want to actually get to better than all of those if you want to be opt 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 like an exercise in 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 prediate 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 control trials

it's cool to see people posting their numbers yeah of things that are not just related to aesthetics but are or body weight but are related to health metrics yeah it's it's 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 them you know not in the red zone but I'm in the like I should probably pay attention to these things yeah 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 in 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 or impacting our mitochondrial metabolic health is the food the sleep the movement the emotional health the toxins are relationship with light and are 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 thing those are the things in our environment that we need to 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 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 a hundred percent molecularly made from food

it's so wild it's so wild every time I think about that it's 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 always you know 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 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 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 health care both our western sort of desperialized 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 the 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 the body it is the cell signaling functional molecules that tell ourselves what to do they act as transcription factors

abgenetic modifiers cell signaling pathway intermediates and it's also of course the substrate to change what the microbiome does and the composition of the myomicrobiome which is basically a pharmacy inside our bodies to create different molecules that can affect our health

so food is certainly a calories a calorie from the concept of thermodynamics but from the concept of molecular information it has 3 massively important parts that are unavoidable for creating cellular health so I would just say that that is the pillar that we can drill

it would be happy to drill into of like what do we really do to you know build 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 under explored topic so with respect to food gosh I feel like we've all been exposed to pretty much every variation of you know

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 I'm not allowed to explore however I can just say for myself for what it's worth I'm not very hungry until 11 am noon or one I'm okay not eating until then and just you know water electrolytes and caffeine does me just fine I can exercise

etc 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 I'm just a 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 process 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 at 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 it 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 your biology neurobiologically your rewards 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 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 net

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 promise 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 a really of any dietary philosophy they want

truly I think if someone's eating real unprocessed food from good soil is you know plant-based or who is keto they are going to have such a higher chance of meeting their bodies 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 moral to process 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 to meet ultra-processed food and for two weeks he had to meet real food and people ate 7000 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 franken food toxic food system that's that's largely ultra-process and it took amazing Kevin Hall to basically do an NIH you know funded study where people what I say by locked is that they were in patients at the NIH

and every had ad lib you know 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 mentally 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 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 two pounds and then lost two pounds in the unprocessed group which makes sense of course because of pounds 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 that our satiety hormones get secreted and we naturally stop eating cause 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-metre tons of food reading in the lifetime

it's just fasting 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-process so we slash the value because the ultra-processing just like slashes the nutrients we slash the value of that 70-metre tons

and then we have crappy soil because our industrial agriculture system which means the food in some cases has 70% less of key micro nutrients in it so that 70-metre 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-3's, 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 on to 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 recovery I'm not just from exercise but just daily turnover, removal of waste etc. 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 I'm not either, you know, I'm not meat based and I'm not plant based I'm in 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 food, 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 rice, oatmeal, some pastas, some sourdough breads

and things that I love butter, who doesn't know butter of course none of that stuff in excess olive oil but if one looks at kind of that buffet of options 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 on to one another and so you can imagine that the neural circuits

and here I'm a little bit of hypothesizing slash conjecture but that the neural circuits responsible for hunger and satiety would get immensely confused by what's in a highly processed food 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 Snickers bar taste 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 or epinephrine acetocholine 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 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 I don't know anyone who have reasonable size that eats like four ribeye steaks you know they eat one I'm sure there's some freaks out there that do that but you know one you know 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 and 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 and you're 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 brand

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 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 z epidemic fundamentally is a lot of it's 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 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 Schatz or he also wrote the Dorito effect but he talks a little bit about what you're talking about

which is the 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 back 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 we think we're eating a tortilla but it's like completely different then 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 going to be but we have no idea is it a Coke zero is it a Diet Coke with Aspertain is it a regular Coke it all tastes the same but the nutrients that are got 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 is 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 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 stimulate the body in a way that it will serve me and 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 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 ozemic and minjar 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 satiety hormones and the process foods aren't giving us those things you know the things that are going to 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 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 GLP1 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 it's 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 met in human history and just like we tied out into the beginning of the episode the whole industry this four trillion dollar 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 of 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

more fiber eat more fiber and we had Justin Saunenberg 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

sourcrout kimchi again low sugar varieties probably best yeah maybe not you said not kombucha yeah that's going to be like the highest sugar of the fermented foods which people often go to but not costly to it yeah the sourcrouts you can actually make your own sourcrout Tim Ferris

that a great recipe for this in the four hour chef you have to be careful because you know that 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 sourcrout and the brines drinking the brine off the sourcrout 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 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 a short-chain fatty acids directly so that's the kimchi

sourcrout Greek yogurt kavas which I'm obsessed with which is like low sugar kambucha it's like made with fermenting beets basically it's such good stuff me so not oh 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 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 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 your rameite 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 you're going to find that in like meat and turkey and eggs and things like that. What are your thoughts on supplementing your glutamine?

It's controversial I know that some people do it in an effort to relieve leaky gut but that's but there aren't any randomized control trials for that so the depending on one stance on what's required for kind of a threshold for for adopting something you know some people say

that's crazy other people really swear by supplementing all glutamine maybe it's through this this route of increasing L cells that some they got relief might exist I guess we'd have to explore it so that's speculative folks so it's interesting these are ways to increase the

cells that then make GLP1 so fiber prebiotic probiotic fiber and fermented antioxidants lowering blood sugar ginseng so those are kind of the L cell ones the actual secretion of more GLP1 that one of the most potent ones and the study that looks at this like the

bar graphs are very clearly statistically significant lots of asterisk is actually thylacoids so I look at me more about phyloids are so fasting thylacoids are actually a structure in plants that are part of the chloroplasts so you know chloroplasts

and this also is fasting is chloroplasts are basically the plant version of mitochondria essentially and thylacoids are a molecule in the chloroplasts and there's actually been research that shows that when you eat about a hundred grams of spinach which gives you

five grams of straight thylacoid 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 full tire secretion so this is in part of the L cell and so this is this equates to 3.5 ounces of spinach a day which is like nothing so just getting

those I think I actually I don't think it actually it might have set in the methods but I would I would imagine raw because you want to get those undenatured thylacoids in the gut so just kind of another and actually thylacoids 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 in 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 thylacoids also fibers been shown specific amino acids so high protein foods things that involve a lot of valine and glutamine green tea and specifically the all that a logic 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 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 muricetin which

is found in berries cranberries and peppers and 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 yourselves 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 it's interesting again these aren't randomized control trials nor they peer reviewed studies but I have a few friends who have known for most of my

life who really struggled with their weight carried a lot of excess weight and we're starting to suffer health issues in their even their 30s but in their 40s and 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 starch isn't 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 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 food and I'm not somebody that like pushes on 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 you know 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 diet and then you're 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 ozempic yeah and its commercial names are I forget what the the ozempic is the commercial name and jaro and will go over and yeah got it is that glp one acts more less as an appetite suppressant right yeah powerful appetite suppressant yeah so many millions of people are now taking

glp one analogs is that right I think there were over 20 million prescription in the United States last year is it expensive it's it's twenty thousand dollars 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 it's now being recommended for people with obesity type to diabetes and then the American Academy of Piatrics recently has talked about giving this to children as young as twelve 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 function is the root cause 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 Tia's waiting 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 you know the reality is 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's immensely profitable for those hundred specialties of health care.

So you know we're living in this matrix in this game of you know a devil's bargain between a $4 trillion health care and pharmaceutical industry and a $6 trillion process food industry that all want us to think that you know the answer is found in a shot and we don't need to change anything about our lifestyle but of course you know these simple habits that we're talking about eating real food moving walking etc. getting out in the sunlight rapidly can increase our mitochondrial capacity

and you know are just the most disruptive thing that we can do you know in our culture today is 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 assaults against these empowering habits

and very in favor of a medication like ozemic and then when you trace you know unfortunately incentives there a huge percentage of these outlets that cover you know ozemic is a miracle drug their bills are treated by pharma 60% of mainstream media advertising budget is

pharma and so you know I just I just say that because I think it's it's a scandal that we give so much air time to these medications and not to simple metabolic habits that can make us feel you know so incredible and and really change our core biology. So walking exercise eating minimally process or non-process foods you also mentioned temperature.

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

way 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 right at least not yet take a GLP analog like ozemic

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 that and one would hope they are if they're already taking these meds or is it the case that when people have a pillar 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 history here I mean you first of all there have been other weight loss medications throughout history that you've talked about in the podcast like the FENFEN and then there was another one I think even before that that made people

their temperature go up that you talk about the two these are I used to work on thermal regulation is an undergrad so a FENFEN was eventually banned because it caused some cardiac issues I believe it was a stimulant for fluoramine to sorry it's not FENFEN fluoramine alone it's a combination

of things it's what's called FENFEN and then Dynitrothenol which was based on the observation that workers and ammunition 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 don't even look it up it's highly deadly don't because the moment people start looking it up they start thinking about dabbling the way the internet is now Dynitrothenol and I think it has to do with sort of processing of the mitochondria I think

this is happening that the electron chains in mitochondria so anyway or free electron look it up yeah excuse me the bottom line here is that there have been plenty of drugs mostly stimulants used to help people lose weight and or that have acted directly on the mitochondria it has not worked out

well historically right it just hasn't and I think that I'm not just going to lump it's a different mechanism so I don't want to lump it in with pass weight log lost drugs however if you look at the trend throughout history the medicalization and

pharmacology towards chronic issues has been an object failure I can 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 ozemic 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 going to go down that wouldn't actually make sense for the business model I mean these are being talked about at the JP Morgan healthcare conferences do you think they're thinking that this is going to

come up I'm at 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 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 going to reduce the rates of the condition so

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 it longer KC doctor means brought me this jar blueberries people that know me know that I am a drive by blueberry eater so

if there's blueberries out on a on a table I'm going to take some I've never eaten during a podcast but I'm going to now so I'm trying to quietly do you want to do you want some I love blueberries and no I don't eat them one by one so I'm going to 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 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 feels good I feel great afterwards for many

hours and I believe there's some health effects and I'm willing to weather the storm of of naysayers because more and more data keep emerging yeah that's the case not all the data are spectacular one paper on this actually was just retracted we need to do an update to an episode to it's not work for my lab but 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 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 concept in human history for walls you know

insulation then central heating and cooling that's like the last 50 75 years in most homes and so this idea ourselves have evolved to respond to big swings and temperature that very recently we have totally pulled away and I think that when I think about the mitochondria and 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 energy 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 right and thermal energies 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 stimulus and so that's kind of the framing that I use for it and like you know this data's hard to know if it's totally accurate but

like our population is is cooling and some I think it was data to Stanford actually that was showing that like our temperature has gone down like 2% or something like that in the last 100 years and that fundamentally is mitochondria not working as well as they should research has shown we're making

less ATP and a lot of ourselves and that's you know function mitochondrial dysfunction 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 constantly recycling it in this like you know like

basically make it use it make it use it make it so fast 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 about to talk to the mitochondria to say

make more heat and you know world in which our mitochondria under siege I think it's a valuable often very inexpensive one that can we can use of course it does not supplement or replace food sleep exercise 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 again the data you know is mixed but like increase brown fat which is like mitochondrial

dense fat and 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 all used 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 talk protein some of which have you know the ability to upregulate antioxidant defense systems and quell some of that wildfire that we talked about that can

hurt our mitochondria 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 I love it I'm I will just point out

that the reason the brown fat is brown at all is because of the density of mitochondria yeah literally brown down the microscope this is not the kind of fat that well is subcutaneous although it you know it sits around the scapular neck up or 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 the best part is getting out and how you feel afterwards but I think it nothing greats 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 a minimal amount of clothing outdoors but there's just such beautiful data from Dr. Susanna Soberge's work showing for instance that deliberate cold exposure then leads to one feeling more

comfortable at cold temperatures because you become a you know a essentially more of a furnace more more 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 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 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 or skipping dinner right sometimes I'll skip dinner sometimes I'll skip breakfast right 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 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 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 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 compressing our eating 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 yeah for me all per day thing is tough I have friends like like Friedman that do the one meal per day I end up eating so much food at that meal that experience a lot of like mechanical distress

and typically later in the day I think an eight to ten-hour window has worked well for me most 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 so 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 six-hour

feeding window I just want to point out we're a 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 yeah it's like the fact that studies that haven't been peer-reviewed aren't even close to being peer-reviewed are 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 the fact of the matter is like until the reviews are done the revisions are made like that paper may never see the light a day and it may end up in a journal that you is barely worthy of a placement it might end up in a high-tier high-quality journal but it might not so just because there was a quote-unquote a study done means very little but it means especially little

maybe nothing until it's peer-reviewed absolutely in the methods were very poor in that study it was a recall based study I think for two days of a 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 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 doing which is the average American has eleven eating events per day and fifty percent of Americans eat over a fifteen-hour window per day I can recall those because I remember when I

was writing the book I was like that's a long time fifteen 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 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 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 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 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 nobicity you know rates in the country is

because with the way the culture of eating right now eleven eating events today eating over the course of fifteen 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 to the

body if you think about again the stats about ultra processed food about 70 percent of the items on the shelves in the grocery store ultra processed food and those ultra processed foods are built on refined added sugars and refined added grains so we're just we've very rarely give the body the opportunity to rest and 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 especially if your body is 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 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's 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 in 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 9.30 a.m. or 8.30 p.m. so basically after dark essentially in the part of the diurnal phase we probably shouldn't be eating versus early in the

morning 9.30 and the glucose and insulin responses for the same meal at 8.30 p.m. were significantly higher than when eating at 9.30 a.m. and so again being 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 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 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 time I aim to do three times a week and post-resistance training I try and get some starchy carbohydrate in that just to replenish glycogen and that's 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 stakes there but they had a new key that

it took everything I had every neural circuit that releases GABA in addition to

my brain to not order three of those orders it was so good. But you can look after the new okay yeah sure I'll allow myself to do all say 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 not take the jar and funnel them into my into my mouth yeah I think you know if we're looking at blood sugar blood

glucose and insulin and as long as we're talking about that I I did use a levels tracker and yeah full disclosure there is sponsor the podcast regularly and I learned a ton I'll tell you I'll tell you what I learned I learned that indeed my blood sugar goes up after I eat that certain foods although the foods that did this surprise me certain foods tend to spike my my blood sugar I'm quite a bit grapes that shouldn't be surprising foods food order was very

powerful for me I know that the date on food order 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 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 gonna turn myself into a brisket 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 is that makes sense it does make sense but also the heat can affect the accuracy of the sensor itself okay so that

could be it to but yeah basically what it allowed me to do is make a few adjustments in terms of foods that I eliminated or 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 correlative anacidata 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 slowly 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 I did this and 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 things that one could do to explore an experiment because I like to explore an experiment yeah well I mean a lot of the things that you just naturally learned are the things that have been shown in data and 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 on lowering glucose response fat probably in some part due to slowing gastric emptying and actually slowing the digest in process so the rise in the blood 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 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 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 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 say the purpose of the glucose non-intern is not to have to game the system and get flat glucose the purpose of 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 stacked against us with that in 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 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 staying out of the diabetic range and so one thing the glucose monitor does for us is just give us more awareness and agency into like what the trends of our glucose are over time as

opposed to a literally one data point snapshot once a year in the doctor's office which is what the majority of us are used to 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 prediabetes 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 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 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 and coming down spike about 45 minutes and come down hour and a half 90 minutes to two hours but 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 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 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 trans-inly 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 a UC after a glucose spike so you want to spike and come down quickly that's going to 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 a UC is associated with insulin resistance basically another thing that you can see is essentially glycemic variability and glycemic variability GV is a metric of

how spiky your curves are fasting paper out of Michael Schneider's lab at Stanford in 2018 called glucose types reveal new patterns of glucose dysregulation totally landmark study but basically they put conclinator glucose monitors on non diabetic individuals who by standard criteria of

diabetes do 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 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 spiky are they are the worst their biomarkers are metabolically across the board insulin triglycerides etc so basically they're 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 going to

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 non diabetic 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 into the curve those are two things another really interesting thing you can know from a CGM is don effect so don 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 notice this when you were wearing a CGM but some people notice

that the second they wake up their 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 got a bed that cortisol can cause you to dump a bunch of glucose from your liver because it's basically saying stress hormone cortisol we got to get up we need glucose to fuel the muscles let's dump a little glucose so it's it's normal but what the research shows is that magnitude of

don effect is correlated with insulin resistance so the more the don 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 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 you're insulin resistant that that response that don effect is going to be higher so I I don't have the

numbers right in front of me but typically I would want to see a don effect I think of like less than 10 points so you wake up and you you may very well see a rise this is absence of any food yet and you do not want to see that going 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 another thing that standard stuff would never tell you so those are kind of some of the looking at early

predictors and 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 enjoy it and like figure out like oh my god this food that I thought was

healthy is actually not you know serving me and actually a lot of people I think we're trying to make healthy choices my boyfriend like he when we started dating he started using yet 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 was a tasty star they do but he would get this green juice that was sweetened with dates and it was like nine dollars and this was like the healthy choice and he saw the second he put on levels that it was causing a huge spike like 50 60 70 points and then he was crashing and he was actually trying 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 ghost stuff that isn't spiking his 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 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 it's really helping with what are the sneaky spikers and then where's the biochemical individuality and there was a phenomenal paper out of Israel that from from Sal 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 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 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 all of those things can positively impact glucose spikes especially the walks after the meals but some 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 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 virtuous cycle so so those are some of the big things those are big I can I mention one more I know I know I just I could obviously talk about this all day I think it's fascinating but this is just one more that I think it's 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 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 baseline so a small spike usually won't need to a crash but a big spike often

will that's called reactive hypoglycemia post-prandial 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 paper showed that the extent of post-meal dips the crash after the spike was predictive of 24-hour energy intake and cravings for carbohydrates and this makes 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 lower the the extent of our spikes so that we crash less and so that was a fasting study looking at CGM data 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 which is you know I don't want to scare people in the thing 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 as a study in proceeds in the national Academy of Sciences I have to go back and check if it included kids but pretty striking and

then it's 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 you know last hour or two of sleep in the morning that resting blood glucose is altered it's so interesting 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 metametabolism they were undergoing and it's interesting during a full-night sleep 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 were metabolite were rely more on let's just call it

sugars for a sake of simplicity other times were more ketone dominant there's a market shifts in metabolism throughout the night it's almost like the brain and body cycle through all the different modes of metabolism throughout the

night and then almost like a rehearsal of the metabolic pathways if you know 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 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 yeah 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 negative potential negative cost there 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 or in our blood because for instance I would love to know continuous hormone levels lipid levels blood blood sugar levels I mean are we moving past just blood glucose and are are there soon to be other things in these monitors so that when we by the way if you haven't used these 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 yeah 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 the 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're 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 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 Dexcom which is the

other main company that makes cgms has just announced they're coming out with an over the counter non-perscription version of a cgm called the Stella later this year so there's exciting things happening in the industry and I I really do think continuous monitoring it's it's going to expand to a lot of these other things that you're talking about hormones etc and I mean it it really needs to I think that you know snapshots of dynamic system are just never

going to really be able to give us a full picture on what's going on and 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 biofeedback 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 yeah let's talk a little bit about mindset this is a really interesting topic that you including 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 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 in one of the favorite passages around that that I really enjoyed was the relationship between like trying to control everything and nature you know and how getting into nature itself can be valuable for us so maybe touch a little bit on mindset if you will and you know what are your thoughts on nature literally getting out

of do it yeah so I think I think that mindset and more broadly than mindset I think psychology 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 a risk factor and stress is a

risk factor in these things and something really fascinating actually with the CGM data 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 diabetes genetic 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 me that biochemically I'm

actually releasing energy stores from my liver glucose to fight some threat that you know I wasn't really aware of so there's there's we definitely understand there's this link here but 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 more than the powerhouses 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 and the threats can be anything they can be a virus they 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 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 something to be afraid of they are going to change metabolic function towards defense alarm threat response and away from repair homeostasis building essentially thriving so our and and 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 ultra processed but we also have this device in our hands literally 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 essentially the traumas and fears of eight billion people all over an entire globe are now ours to process 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 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 the 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 on resolve childhood trauma like something that I think is getting a lot more talked about these days but like what's embedded in our

nervous system these limiting beliefs and memories that are really wired that create a sense of hypervigilance and 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 a big western one that we don't talk about is literally like existential feel of fear of mortality we have a very desperialized very uniquely death fearing culture like you look at other cultures eastern indigenous the

Stoics they all had intense curiosity about death we talk about the cycles of life there's this real engagement with it that we are so afraid of in the in the western system to the extent that our entire health care system actually I think you know we've built it around like we're not gonna we're

not gonna help you thrive we're just gonna do whatever we can to make sure you don't die like that's it's built in everywhere and so we've got the devices we've got the childhood trauma we've got the fear of mortality we have a very poor system of mental health care in the culture and I think that

through all these things Americans are getting crushed mindset and psychology wise and that is a big big trigger of our mitochondria essentially diverting resources towards defense threat and alarm rather than homeostasis building repair so again it comes back to

taking really honest stock of what are the true fear triggers in our lives across those and others and creating a sense of safety in our minds and bodies no matter what the external world looks like which may mean putting boundaries up to you know

the media doing the therapy doing the different modalities what I believe and I talk about in the book getting back to the question about nature is one of the best things that we can do is actually literally just go outside and I it sounds so simple but

one of the most astonishing stats I literally found in researching this entire book was that the average American is spending 93.7 percent of their time indoors wild 93.7 that's in a car or in a building so we are locked in these cages staring at fear-inducing media and our

mitochondria are like what like what I don't know where to channel my energy it's just it's short circuiting I think so many things happen we go outside as you know I mean even what the vision system is doing to our anxiety levels we are getting sunlight which of course for

for you know complex reasons is very helpful for our metabolic health separately in trains are you know chronobiology and you know light light from the sun as an incredible regulator of our mitochondrial function but it also it's our best

teacher you know when we're out in nature and we really look at how beautiful the world is and the cycles of nature we see the cycles of you know the seasons and we see the awe of the sun and the trees and just all this alchemy that's happening outside of us we see you know spring to

summer to fall to winter we see the tides moving in and out everything's in phases and I think when we reflect and meditate on all the cycles and the polarities in nature night and day cold and hot new moon you know quarter moon full moon you know all these things

it's actually it entrenched on a subconscious and conscious level that there is a fundamental harmony and pattern to the world we're living in that is bigger than us and that is fundamentally good and beautiful and we are locked inside of the four walls of our house I think we

get very scared we get very controllable and the system wants it that way because when we are scared and when we are existential afraid we will literally do anything we will buy anything do anything watch anything that will in some way

ameliorate that pain that we're feeling and we will take any pill we'll get any surgery anything that makes us feel like we're controlling this seemingly out of control situation and that's what drives us into all the dopamine loops you know the social media the processed food the

porn the gambling the alcohol all of it it's all to ameliorate I think ultimately fear and I think yeah I think by actually really just spending a lot more time trying to get that 93.7% down to like 50% spend as much time as you can outside we know that people who spend more time outside are

metabolically healthier and I think it's for pleiotropic reasons but I think one of it is that it is the ultimate convincing of abundance and fundamental abundance in our world and of awe which I think is really the antidote to fear and that has a profoundly soothing effect on our

psychology and the sense of scarcity that drives a lot of the decisions that actually make us unhealthy it's fundamentally rooted in in scarcity and I think also when we realize we are part of nature again going back to that Taoist statement we're a process not an entity realizing like you know all the trees around us and we take that walk even in a city we see all the trees all those plants all those leaves are making the oxygen that process that literally let us do oxy if

us for a lesion and that sun and that leaf on the tree the sun's energy is literally being stored in the carbon carbon bonds that the plants are generating a photosynthesis that ultimately all metabolism is is unlocking the potential energy stored from the sun to create the human energy

that lets us love and move and live and think and do all the things we love to do and then it just becomes so obvious like of course we have to like eat real food and of course we have to not poison our soil with pesticides and of course

we have to like you know care about the environment and we have to get outside and move and we have to be in the sunlight during the day because we are the environment we are a process that's constantly in dynamic conversation with it and um i think i think a lot of people will find that their

health gets a lot better if they spend a radically more time outdoors and i think a lot of people might say like can't i work on a computer and i'm like you know Rome is burning like we're sick as hell right now we need to get creative like move your computer outside take a walking

meeting open your mail outdoors chop your vegetables on your balcony at your apartment like we we have to find a way to connect back with our source understand that the world is abundant and harmonious uh re-intrench the belief

in our connection with nature and then let all of our dietary and lifestyle strategies stem from that sense of gratitude and awe and that will lead us right where we need to go which is um a really i think joyful experience of our health journey um that's rooted fundamentally in

connection rather than us being siloed from all of this which going back to being in the conversation that's fundamentally what's wrong with the health care system it silos and we have siled ourself from all of the life giving things in our environment and that has ultimately led us to be very

very very sick and we just i think we got to go back outside so that's one of the things but there there's many other things we can do to change those our relationship with fear but um we can't change the world as a whole but we can change what happens inside our body in terms of how we

respond to it and for our mitochondria's sake we have to we have to create a sense of safety in our bodies for our mitochondria to do the work we need them to do for health i love it and i love it for many reasons i i think um

it was my i know it was my friend and former guest on this podcast Rick Rubin who several times early in our friendship he said um back to nature the only truth um and i asked him when he meant by that and you know because Rick can be a little bit i'm cryptic sometimes um not always but

sometimes and what he was saying is you know it's a real thing you know you can immediately feel the connectedness between the human experience and um life of other types plants animals you know sunlight the circadian rhythms and

the and the rhythms of the of light and dark um because they impact us so powerfully i mean if the if there were ever a force in the world that impacts how we feel it's the circadian rhythm it's the rising and setting of the sun it's on the impact of light and dark and then all the other things that

you talked about today um i can't help but reflect on kind of your take on kind of what a lot of not all but a lot of modern society attempts to do um it attempts to do a lot of good things too i believe i'm a believer in technology um but that it if i were to translate it sounded like um

what you were saying is that it gives us a sense of loss of control by instilling fear like we don't have control and then um there are a number of let's just call them programs in the world um that that then sell back the illusion of some sense of agency little by little right

a temporary agency and then puts you back into the cycle and there's something about going into nature which just um removes one from all of that at least temporarily gives you a more basic understanding of the relationship to self and things around us even just looking being able to

see it to a distance we know is powerful for the the brain reducing anxiety we know being outdoors for two hours or more per day reduces my opian nearsightedness this is independent of all the other effects of of circadian rhythms etc anyway and on and on so i second and third and

and uh here here all the um all the statements you made before i also just have to say i really appreciate how you are able to tackle the cellular biology the molecular biology the macroscopic things that we can all do walking resistance training um cold exposure sleep um high-intensity

interval training um and make and make a case for each and all of those as it relates to the underlying biochemistry and we've all that together in a way that then uh you beautifully wrapped into this idea of connecting to nature and not divorcing ourselves from modern life but really

looking at the ways in which certain components of modern life are really making us sick not just the the behaviors not just the do's and the don'ts that it's kind of imparting on us but also kind of the psychology around it it's uh that it is quietly but powerfully oppressive is the is the message

that i'm getting and that we have to take a stand against it and the way to take a stand against it is to do what are very um basic and fairly easy to access things making better choices about food timing quality amount exercise and on and on so so i'm running long in my response to your

much more eloquent a description of mindset um but what i want to say is on behalf of myself and everyone listening i so appreciate we appreciate the work that you're doing to be a medical doctor specialized in one of these silos and then to take a step out and say nope not me i'm going to do

what i see as best for the greater good in terms of giving people tools giving people a sense of agency and autonomy to take control of their health this isn't some ways a heretical idea um but luckily the numbers of folks like you are growing and you're a real leader in this field by example

and by the incredible work you're doing with technology and information sharing love love love the book i did go through it um front to back um i haven't tried the recipes yet but thank you for bringing the blueberries i'll try the recipes um at least one of them and um i just want to thank

you for sharing what you do and um for continuing to do what you do we we need it and we appreciate it so thank you thank you for joining me for today's discussion about metabolic function with dr kacy means if you're learning from and or enjoying this podcast please subscribe to our

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