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

1. 0:00 – 2:18

   Dr. Casey Means

   1. AHAndrew Huberman0:00

      (uptempo music) 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. Casie Means. Dr. Casie Means did her undergraduate degree at Stanford University and her medical degree at Stanford University School of Medicine. She is one of the world's foremost experts in metabolic health. Today, we discuss how metabolic function and dysfunction impacts our health. In particular, we discuss mitochondria, which are involved in energy production within our cells, and the various things that we can each and all do to ensure proper mitochondrial function, which is essential not just for things like body composition and physical and mental energy, but also our ability to regulate hormones, blood sugar, and much more. We discuss how exercise, even simple exercise like walking, as well as sleep, as well as more vigorous exercise, and in particular nutrition, including the types of 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 our cells, 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 and body that underlie metabolic disease and metabolic health. And most importantly, you'll have a very clear picture of the actionable items that we can each and all carry out every day and every week in order to ensure metabolic health, proper mitochondrial function, and indeed that can also impact body composition and overall feelings of well-being. I would also like to share that Dr. Casie Means has a terrific new book coming out. I know it's terrific because I've read it. It is entitled Good Energy: The Surprising Connection Between Metabolism and Limitless Health. If you're interested in the book, we provided a link to the book in the show

2. 2:18 – 6:32

   Sponsors: Maui Nui, Eight Sleep & AeroPress

   1. AHAndrew Huberman2:18

      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. In keeping with that theme, I'd like to thank the sponsors of today's podcast. Our first sponsor is Maui Nui Venison. Maui Nui Venison is the most nutrient-dense and delicious red meat available. I've spoken before on this podcast and with several expert guests on this podcast about the fact that most of us should be seeking to get about one gram of quality protein per pound of body weight every day. Not only does that protein provide critical building blocks for things like muscle repair and synthesis, but also for overall metabolism and health. Eating enough quality protein each day is also a terrific way to stave off hunger. One of the key things, however, is to make sure that you're getting enough quality protein without ingesting excess calories. Maui Nui Venison has an extremely high-quality protein-per-calorie ratio such that getting one gram of protein per pound of body weight is both easy and doesn't cause you to ingest an excess of calories. Also, Maui Nui Venison is absolutely delicious. They have venison steaks, they have ground venison, and they have venison bone broth. I personally like all of those. In fact, I probably eat a Maui Nui venison burger pretty much every day, and occasionally I'll swap that for a Maui Nui steak. And if you're really on the go, they have Maui Nui venison jerky, which has 10 grams of protein per stick at just 55 calories. If you'd like to try Maui Nui Venison, you can go to mauinuivenison.com/huberman to get 20% off your first order. Again, that's mauinuivenison.com/huberman. Today's episode is also brought to us by Eight Sleep. Eight Sleep makes smart mattress covers with cooling, heating, and sleep-tracking capacity. Now, I've spoken many times before on this podcast about the critical need to get sleep, both enough sleep and enough quality sleep. When we do that, everything, our mental health, our physical health, performance in any sports or school, et cetera, all get better. And when we're not sleeping well or enough, all those things suffer. One of the key things to getting a great night's sleep is that your body temperature actually has to drop by about one to three degrees in order to fall and stay deeply asleep. And in order to wake up feeling refreshed, your body temperature actually has to increase by about one to three degrees. One of the best ways to ensure that happens is to control the temperature of your sleeping environment. And with Eight Sleep, it makes it very easy to do that. You program in the temperature that you want at the beginning, middle, and end of the night. You can even divide the temperature for two different people w- if you have two different people sleeping in the bed. And it tracks your sleep. It tells you how much slow-wave sleep and rapid eye movement sleep you're getting. It really helps you dial in the correct parameters to get the best possible night's sleep for you. I've been sleeping on an Eight Sleep mattress cover for well over three years now, and it has completely transformed my sleep for the better. If you'd like to try Eight Sleep, you can go to eightsleep.com/huberman and save $150 off their Pod 3 cover. Eight Sleep currently ships in the USA, Canada, UK, select countries in the EU, and Australia. Again, that's eightsleep.com/huberman. Today's episode is also brought to us by AeroPress. AeroPress is like a French press, but a French press that always brews the perfect cup of coffee, meaning no bitterness and excellent taste. AeroPress achieves this because it uses a very short contact time between the hot water and the coffee. And that short contact time also means that you can brew an excellent cup of coffee very quickly. The whole thing takes only about three minutes. I started using an AeroPress over 10 years ago, and I learned about it from a guy named Alan Adler, who's a former Stanford engineer who's also an inventor. He developed things like the Aerobie Frisbee. In any event, I'm a big fan of Adler inventions, and when I heard he developed a coffee maker, the AeroPress, I tried it, and I found that indeed it makes the best possible tasting cup of coffee. It's also extremely small and portable, so I started using it in the laboratory, when I travel on the road, and also at home. And I'm not alone in my love of the AeroPress coffee maker. With over 55,000 five-star reviews, AeroPress is the best-reviewed coffee press in the world. If you'd like to try AeroPress, you can go to aeropress.com/huberman to get 20% off. AeroPress currently ships in the USA, Canada, and to over 60 other countries around the world. Again, that's aeropress.com/huberman.And now for my discussion with Dr. Casey Means.

3. 6:32 – 14:17

   Metabolism, Metabolic Dysfunction, Medicinal Blindspot

   1. AHAndrew Huberman6:32

      Dr. Casey Means, welcome.

   2. CMDr. Casey Means6:34

      Dr. Andrew Huberman, thank you so much for having me.

   3. AHAndrew Huberman6:36

      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.

   4. CMDr. Casey Means7:16

      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 the bubbling up of all of those chemical reactions is our lives. And so when metabolism is not working properly, it's essentially creating underpowered cells, and like any city or factory or machine, not having adequate power will lead to dysfunction. And the reason that the metabolic spectrum of disease is so vast is because we have over 200 cell types in the body, and underpowering in different cell types is going to look like different symptoms because underpowering in a astrocyte is gonna look different than underpowering in a ovarian theca cell or an endothelial cell. It's going to look different, but the core foundational process that is dysfunctional can actually be the same. And I think the biggest blind spot in Western healthcare, and actually the reason that health outcomes are actually getting worse every year in the United States is because fundamentally, we are ignoring metabolic health and metabolic dysfunction. We are laser focused on the downstream symptoms that result from metabolic dysfunction in different cell types, and we spend all of our energy, uh, focusing on those symptoms, playing Whac-A-Mole with them, and really ignoring that underlying foundational root cause of metabolic function. And what's so fascinating to me and what I saw in the healthcare system as like a super subspecialist, as an ENT surgeon, is that, you know, the more we specialize in healthcare, we have over a hundred specialties now that we've just like invented in the healthcare system. The more we specialize in healthcare, the sicker we're actually getting. So the more we do technological innovation in all these different specialties, the sicker we're getting. And I think what, what the real nugget there that, that everyone really needs to understand is we've bought into a system where we value specialization, and this is the game in Western medicine. But while we've done that, what has happened is we have the worst chronic disease epidemic and the lowest life expectancy of any high-income country in the world. And the reason is because in that specialization, we're focused on the downstream manifestation of underpowering of cells, the, the cell-specific symptoms and not the metabolic function itself. So really our chronic disease epidemic in this country, it is a metabolic dysfunction epidemic and underpowering epidemic, and that is the biggest blind spot in healthcare. And I think a focus on metabolic function as the center of our healthcare system, it's a completely new paradigm for health that is urgently, and I cannot overstate enough, it's urgently needed. We know we're not in the right paradigm right now when we have a hundred isolated specialties and yet 85 to 90% of the conditions in those specialties, if you go to the science and look at the real physiology, is metabolic dysfunction. So, that's kind of the landscape of what metabolic dysfunction is and how it's kind of creating a, 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.

   5. AHAndrew Huberman12:40

      Yeah, thank you for that. I have, um, several reflections and a question. Uh, first off, the, 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.

   6. CMDr. Casey Means12:59

      Yeah.

   7. AHAndrew Huberman12:59

      Tires aren't aligned, engine isn't working well, transmission isn't working, a bunch of issues. And no factory, no car manufacturer would tolerate that, nor would the customers, but we're tolerating that in ourselves, it sounds like. Many people are.

   8. CMDr. Casey Means13:15

      Yeah.

   9. AHAndrew Huberman13:16

      And then accepting the fact that then a bunch of other businesses are gonna crop up, like the business that aligns the tires, the business that goes and repairs the pistons. And, and essentially, when you talk about these multi-specialties that have evolved in the, in the medical care system, they provide an opportunity to go and fix the problems or try and ameliorate the problems, but really what we need to do, to make this analogy, uh, much briefer than it would otherwise would be-

   10. CMDr. Casey Means13:40

       (laughs)

   11. AHAndrew Huberman13:40

       ... is just to go further up the assembly line, figure out whether or not the hardware is correct, the software is correct, and where the hardware and software are becoming deficient in this, um, 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-

   12. CMDr. Casey Means14:00

       (laughs)

   13. AHAndrew Huberman14:00

       ... 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-

   14. CMDr. Casey Means14:11

       Yeah.

   15. AHAndrew Huberman14:11

       ... and repair metabolic dysfunction, essentially make us metabolically functional. So, um,

4. 14:17 – 24:02

   Trifecta of Bad Energy

   1. AHAndrew Huberman14:17

      the question therefore is, I think most people when they hear metabolism, they think energy.

   2. CMDr. Casey Means14:24

      Yep.

   3. AHAndrew Huberman14:25

      And when we hear energy, we think ATP sometimes, but typically people think about mitochondria.

   4. CMDr. Casey Means14:32

      Mm-hmm.

   5. AHAndrew Huberman14:32

      Right? The powerhouse of the cell, so to speak. Um, so you've talked about the trifecta or the-

   6. CMDr. Casey Means14:38

      Mm.

   7. AHAndrew Huberman14:39

      ... 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-

   8. CMDr. Casey Means14:57

      (laughs) Yeah.

   9. AHAndrew Huberman14:57

      ... that we can actually take some control, that we have some agency in all of this, which I believe we do. So if you would, could you get us all on the same page about, you know, what are mitochondria and what do they do? Why are they so important?

   10. CMDr. Casey Means15:08

       Mm.

   11. AHAndrew Huberman15:08

       Then we can turn to inflammation and oxidative stress.

   12. CMDr. Casey Means15:10

       Yes. Absolutely. So, the mitochondria or, are the structure within the cells. We have 40 trillion cells, and each cell might have a handful or many thousand mitochondria, and they are the magical part of the cell that does that conversion process of food breaking down, uh, and then converting to energy, to translating it to a currency of energy our body can recognize. And so currently what's happening is that our environment, the environment that our cells exist in across every single facet of our life over the past 50 to 75 years has changed rapidly. You look at how our food system has changed from whole real food and good soil to industrial food. Our sleep habits have changed. We're sleeping less. It's very fragmented. Our movement patterns have changed. We're sitting 80% of the waking day. Our time in nature has changed. We actually are indoors as Americans 93% of a 24-hour period, so that totally changes our relationship with light. We have 80,000 synthetic toxins in our food, water, air, personal care products, home care products. We live a thermoneutral existence now with our thermostats. There's no real swings in temperature unless you're intentionally trying to. Um, and then our emotional health is very different. We are very much exposed to low-grade chronic stress triggers. So across food, sleep, movement, emotional health, toxins, light, and temperature, things are not what they once were, and it's changed in the blink of an eye. I mean, the light bulb was created in 1806. This is like 0.04% of human history that we've even had artificial light. So things have changed and the, 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, 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 gonna be stored, and that's of course why we have an obesity and overweight epidemic that's affecting close to 80% of Americans.

   13. AHAndrew Huberman17:50

       That's so wild.

   14. CMDr. Casey Means17:51

       It's, 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, I had trained as an ENT surgeon and I was at Stanford Medical School, and I, I was so fascinated by this idea of like the way that we're defining the diseases we're treating in these, in, in like a specialty like ENT is like I, I saw sinusitis day in and day out, and we'd have these patients on the table that we'd be literally drilling into their skulls to suck out sinus pus, and that's like the treatment for sinusitis. And the way we diagnose the patients is we say like, "Okay, this patient has sinusitis if they have facial pressure."... purulent pus, you know, nasal discharge, um, 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 chron- you know, sinusitis is a chronic inflammatory condition, where the cells are essentially sensing some threat, and then they mount this immune response that creates swelling, and then you get pus buildup. But we confuse the pus buildup with the disease, which is actually happening inside the cells. And so, you start looking at PubMed as a, 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 U- US is that you will find a lot of papers on how the mitochondria are dysfunctional, lower ATP generation in a lot of these cell types. And then, what does that do? And this gets to your question about chronic inflammation and oxidative stress. Well, when you've got that dysfunctional mitochondria, let's say in a nasal mucosal tissue, that is a cell that can't do its job. That is a cell that's underpowered, and what could be more threatening to the body than a cell that can't do its job? So, interestingly, those cells will initiate a whole process which is called the cell danger response. Um, it's work that's been done by Robert Naviaux at, uh, UCSD, where basically they understand the mitochondria is not working properly. This is, of course, caused by the environment, and they will actually release extracellular ATP, which is not really supposed to go outside of the cell. And that creates a massive innate immune response saying like, "I'm underpowered. I need help. My mitochondria is broken." This is the cell. Releases ATP outside of the cell. Usually, the concentration of ATP is a million times higher inside the cell. So, releases it almost as a neurotransmitter, a purogenic neurotransmitter that massively activates the immune system to come and help. But the immune system comes and is like, "Not much we can do for you here," because the problem is not something that the immune system can help with, like grabbing a bacteria and lysing it or, you know, taking care of some cells in- infected with a virus. The problem is outside the body. It's the environment. So, you end up getting this tornado of dysfunction, of mitochondrial dysfunction caused by the environment, leading to the cell danger response, which leads to innate immunity. And then on top of this, you get the oxidative stress, which is the third piece of the trifecta, which is essentially these mitochondria trying so hard to do their work, but they're not working properly. So, they create damaging metabolic byproducts called oxidative stress, free radicals that cause more damage. So, this is happening in the nose. It's happening all over the American body because of our environment. So, you've got these tornadoes of interrelated physiology of mitochondrial dysfunction, chronic inflammation, oxidative stress, which if you start going to the research as a clinician who's focused on symptoms and confusing those for the disease, and look at, what's the pathophysiology of arthritis? What's the pathophysiology of Alzheimer's dementia? What's the pathophysiology of type 2 diabetes, obesity, fat, fatty liver disease, polycystic ovarian syndrome, erectile dysfunction? It all traces back to this trifecta that no medication or surgery ... You obviously can't operate on oxidative stress. You can operate on the downstream symptoms. So, that's the real secret that I really feel like we need to reorient the healthcare system around, since 90% of healthcare costs go towards treating the downstream symptoms of these. And for every marginal dollar we're spending on treating symptoms, we're getting si- 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. It's response to a threat. Mitochondrial dysfunction is kind of like rolling blackouts. It's not enough power. And the oxidative stress is like wildfires. So, it's kind of ... What's funny to me a little bit is like what's happening inside the cell is almost like what's happening, 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, uh, again, the optimistic news that you alluded to is that we actually have tons of tools and tests that can actually help us understand our level of metabolic health, and even give us hints about inflammation, oxidative stress, and mitochondria dysfunction. And it's very easy to improve if we know what we're actually focused on.

5. 24:02 – 27:57

   Western Living, United States, Specialization & Medicine

   1. CMDr. Casey Means24:02

   2. AHAndrew Huberman24:02

      Well, that's reassuring, and we're definitely gonna go there. Um, I appreciate the analogy to living in California. I've lived here my entire life.

   3. CMDr. Casey Means24:09

      (laughs)

   4. AHAndrew Huberman24:09

      I have been outside of California, but, um, perhaps the only thing you left out, um, bes- besides rolling blackouts, fires, and what was the other one?

   5. CMDr. Casey Means24:17

      Fear.

   6. AHAndrew Huberman24:17

      And fear is, uh, high taxes. The taxes are the health debt on the, on the, on the body. So-

   7. CMDr. Casey Means24:21

      (laughs)

   8. AHAndrew Huberman24:22

      ... um, in any case, not to be too dark and pessimistic-

   9. CMDr. Casey Means24:24

      Well, that's the healthcare cost, Andrew.

   10. AHAndrew Huberman24:25

       I maintain great hope and, and still a lot of love for California, you know?

   11. CMDr. Casey Means24:29

       It's pretty great.

   12. AHAndrew Huberman24:30

       It- it's got its great aspects and its not-so-great aspects. And I can say that as a lifelong California resident. Um, there are other wonderful places to live. A couple of, uh, questions. First of all, about places to live, you've been talking a lot about in the United States.

   13. CMDr. Casey Means24:43

       Yeah.

   14. AHAndrew Huberman24:43

       Are some of these same issues with metabolic dysfunction occurring outside of the United States? I would imagine so.

   15. CMDr. Casey Means24:49

       Yep. Any country where we've exported the standard American diet and some of the other-... norms of Western living are starting to see the s-same rates, uh, of, of chronic disease. But, like, it is n- worth not mincing 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 healthcare than the second-highest spending country in the world. So we are, we are abjectly failing, and that failure is predicated in our cult of siloing conditions 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 their 10 different symptoms are separate things, then they're going to 10 different specialists' office. Meanwhile, 75% of American adults are overweight and obese, some of the highest in the world. Um, a full 50% of American adults now have pre-diabetes and type 2 diabetes. 50%. 30% of teens have pre-diabetes. 40% of Americans have a mental health diagnosis. Cancer is set to reach two million cases this year in 2024, highest ever in recorded history. Alzheimer's is going up. Fatty liver disease is affecting 40% of adults, 18% of teens. Autoimmune disease is skyrocketing. Infertility is going up at huge rates. All these things are going up all at once in the US and, yes, in many of the other countries that are eating our diet, um, and there's no sign of it slowing down. And so that's really... Uh, 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.

   16. AHAndrew Huberman27:03

       Scary picture.

   17. CMDr. Casey Means27:05

       (laughs)

   18. AHAndrew Huberman27:05

       I'm glad that you're-

   19. CMDr. Casey Means27:05

       But hopeful-

   20. AHAndrew Huberman27:06

       Uh, but hopeful.

   21. CMDr. Casey Means27:07

       ... 'cause we can fix it. (laughs)

   22. AHAndrew Huberman27:07

       Exactly. I'm glad that you are, um, creating solutions. And, 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? Um, 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 a MD and are, are highly trained. You were an ENT, ear, nose, and throat doctor.

   23. CMDr. Casey Means27:34

       Mm-hmm.

   24. AHAndrew Huberman27:34

       So if anyone would be familiar with the industry and the practice and the educational system around this, it's you.

   25. CMDr. Casey Means27:42

       Yeah.

   26. AHAndrew Huberman27:42

       So, uh, you're not speaking outside your bailiwick. So before we pivot to solutions-

   27. CMDr. Casey Means27:48

       Yeah.

   28. AHAndrew Huberman27:49

       ... 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, um, some of the issues here just a little bit more.

6. 27:57 – 33:33

   Insulin Resistance, Tool: Mitochondrial Capacity & Exercise

   1. AHAndrew Huberman27:58

      You talked about underpowered cells.

   2. CMDr. Casey Means28:00

      Yeah.

   3. AHAndrew Huberman28:00

      You've also alluded to the fact that most people are consuming enough and probably excess amounts of caloric energy.

   4. CMDr. Casey Means28:06

      Yes.

   5. AHAndrew Huberman28:08

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

   6. CMDr. Casey Means28:25

      Yeah.

   7. AHAndrew Huberman28:25

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

   8. CMDr. Casey Means28:29

      Yeah.

   9. AHAndrew Huberman28:29

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

   10. CMDr. Casey Means29:20

       This is the key question for how we can get healthy, and it's really about creating capacity in the body to turn more potential energy to usable energy, as opposed to taking that potential energy and shunting it to a storage form. It's all just... Like, I think about everything visually, and I'm like, you got the circular cell from high school biology textbook. Inside are all the little mitochondria with the squiggly lines inside, and it's just like there's Xs 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, 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 gonna take the substrates, and I need to block them." And you've got to turn them to basically a storage form, which inside the cell could be toxic fats, like ceramides and diacylglycerol. And I'm also going to block the cell from taking any more substrates, because I can't do anything with them. That is fundamentally root of insulin resistance. So the body says, "Okay. We're gonna block the ability of the insulin receptor to transduce its intracellular signaling pathway. We're gonna block it, and when that insulin binds, we're not actually gonna 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, it, it, you know, that it's not going to be functional, and so you don't get the glut for- you don't get the glut 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 a 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 mitophagy, the recycling of o- old mitochondria to, to new mitochondria. It means promoting mitochondrial biogenesis. It means increasing the oxidative capacity of our individual mitochondria. It means improving mitochondrial fusion, which is actually when mitochondria come together to form long chains of mitochondria that are more efficient. So there's, like, a lot of technicality to, like, what it means to print more mitochondria, have them each be more efficient, and have each one do more work, but that's really what we want to do, and that's when it just kind of gets into the simple habits. Like, there's simple things we can do for each of those things. For mitophagy, you know, we can focus on various types of, like, endurance exercise and, uh, high-intensity interval exercise. There's compounds like Urolithin A that promote mitophagy. Um, 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 7,000 steps a day have a 50 to 65% lower chance of dying in 10-year follow-ups, and it's like, yeah, because walking is literally a glucose disposal signal, so you're just simply asking ... It's not a great biogenesis signal, it's not a great mitophagy signal, but it's a great disposal. So if you're doing lifestyle habits that do one of those three things, which we can, of course, go into more, you're improving the cell's capacity to, um, do that conversion process better.

7. 33:33 – 35:03

   Sponsor: AG1

   1. CMDr. Casey Means33:33

   2. AHAndrew Huberman33:33

      I'd like to take a brief break and acknowledge our sponsor, AG1. By now, most of you have heard me tell my story about how I've been taking AG1 once or twice a day every day since 2012, and indeed, that's true. I started taking AG1, and I still take AG1 once or twice a day because it gives me vitamins and minerals that I might not be getting enough of from whole foods that I eat, as well as adaptogens and micronutrients. Those adaptogens and micronutrients are really critical because even though I strive to eat most of my foods from unprocessed or minimally processed whole foods, it's often hard to do so, especially when I'm traveling and especially when I'm busy. So by drinking a packet of AG1 in the morning, and oftentimes also again in the afternoon or evening, I'm ensuring that I'm getting everything I need. I'm covering all of my foundational nutritional needs, and I, like so many other people that take AG1 regularly, just report feeling better. And that shouldn't be surprising because it supports gut health, and of course, gut health supports immune system health and brain health, and it's supporting a ton of different cellular and organ processes that all interact with one another. So while certain supplements are really directed towards one specific outcome, like sleeping better or being more alert, AG1 really is foundational nutritional support. It's really designed to support all of the systems of your brain and body that relate to mental health and physical health. If you'd like to try AG1, you can go to drinkag1.com/huberman to claim a special offer. They'll give you five free travel packs with your order, plus a year supply of vitamin D3 K2. Again, that's drinkag1.com/huberman.

8. 35:03 – 44:25

   Tools: Walking & Glucose; Frequent Movement

   1. AHAndrew Huberman35:03

      There's a lot of great science and a lot of, um, great stuff related to testing and assessment of one's metabolic health that we should get into and will get into.

   2. CMDr. Casey Means35:14

      Yes.

   3. AHAndrew Huberman35:14

      But since we touched on lifestyle and because we've been talking about the sort of dysfunctional dark side for a bit, maybe we could just touch on some of the lifestyle factors that you just mentioned-

   4. CMDr. Casey Means35:25

      Yeah.

   5. AHAndrew Huberman35:25

      ... um, 'cause I do think it's important that people really start to feel into their sense of agency, and here we're talking about, um, 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. Um, again, I, I want to point out that these are not, like, strict prescriptives, but-

   6. CMDr. Casey Means35:47

      Yeah.

   7. AHAndrew Huberman35:47

      ... if you had a magic wand, and because you are interested in the health of humans, um, let's talk about a few of these things that can improve, um, glucose disposal-

   8. CMDr. Casey Means35:58

      Mm-hmm.

   9. AHAndrew Huberman35:58

      ... um, and mitochondrial function, uh, mitophagy, the removal of, of dead or dysfunctional mitochondria so they can be replaced. Um, let's talk about the walking one first.

   10. CMDr. Casey Means36:07

       Yeah.

   11. AHAndrew Huberman36:08

       You said 7,000 steps a day. I don't track my steps.

   12. CMDr. Casey Means36:10

       Mm-hmm.

   13. AHAndrew Huberman36:10

       Um, what are we really talking about there? Are we talking about taking the stairs and trying to walk as much as possible? Maybe we, like, if we were going to just give, like, a really crude prescription. You're a doctor, so you can prescribe things.

   14. CMDr. Casey Means36:19

       Yes.

   15. AHAndrew Huberman36:20

       Um, what would you tell people to do? Like, how many short walks per day? Is, is it, like, three? Is it five? Is, um ... What are we talking?

   16. CMDr. Casey Means36:27

       I would say, uh, I mean, at- at least three. I would say aiming for more than that is good though. There's ... So, so to sort of just give a sense of the picture of walking, i- if walking were a pill, it would be the most, uh, impactful pill we've ever had in all of modern medicine. Um, there was a paper in JAMA, uh, 6,300 participants followed for, uh, 10 to 11 years, and the people who simply walked 7,000 steps per day compared to less than that had-... in up to 70% lower risk of all-cause mortality in the follow-up period.

   17. AHAndrew Huberman37:05

       Amazing.

   18. CMDr. Casey Means37:05

       So not causality, but it's, it's pretty incredible. They've done follow-up research with slightly different numbers showing, again, though, like many thousands of people, uh, in the study, followed for about 10 years, 8,000 to 12,000 steps per day was associated with 50% to 65% lower, uh, all-cause mortality. And this has been played out in many studies showing about a 50% reduction in Alzheimer's, uh, dementia, obesity, type two diabetes, depression, cancer, gastric reflux, just all across the board. And I think the key thing is that it's not about the steps. (laughs) It's about the fact that muscle contraction is medicine. When we contract our muscles, even in a very, like, low-grade way, like walking or doing a couple air squats, you know, we're activating AMPK, and we are essentially causing that cell to have a stimulus to push glucose channels to the cell membrane. Most of the time, the glucose channels are, like, in vesicles, inside, in little bags inside the cells. They're not on the cell membrane. So, of course, that's going to keep the, the glucose in your, 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 pushup breaks or air squat breaks every 30 minutes or so throughout the day as me, essentially, inside the cell, pushing the glucose channels of the cell membrane to make them constitutively active. Um, 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, and this has been shown out in actually more clinical research, which has taken ... There's been several studies. Two that I think are fascinating, where they basically took two groups and they said, "Okay, we're 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."

   19. AHAndrew Huberman39:48

       So, these are three separate groups.

   20. CMDr. Casey Means39:49

       Three separate groups.

   21. AHAndrew Huberman39:50

       So it's tw- either 20 minutes before, ei- either 20 minutes after, or ...

   22. CMDr. Casey Means39:53

       Two to three minutes every 30 minutes.

   23. AHAndrew Huberman39:55

       Okay.

   24. CMDr. Casey Means39:55

       All added up to 60 minutes of walking or light jogging a day. I'm kind of paraphrasing two different studies that showed the same thing. One was jogging, one was walking, but it was basically chunks versus short walks every 30 minutes throughout the waking day. The groups that do the short movement regularly throughout the day, even though the total time is the same across all the groups, have significantly lower 24-hour glucose level averages, 24-hour insulin level averages. They are metabolically healthier, and I believe, and the research mechanistically has shown, that it's because we're constitutively putting this, th- these channels at the membrane to take up the substrate, use the substrate. So, this is not in, uh, to, to replace exercise, but I think it's a reframe. I think the concept of exercise is something we're really very wedded to in our Western culture, and you look at more, like, the Blue Zones and the centenarians, and it's like their kind of moving is built into their everyday life. So, we've taken movement out of our everyday life as these knowledge workers, as we've been industrialized, and then we think that exercise replaces that all-day movement. But biochemically, it does not. So, I think a big part of kind of digging ourselves out of this kind of 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 at the membrane, get the mitochondria active. So, a- 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.

   25. AHAndrew Huberman42:00

       Very interesting, 'cause I think a lot of people are now working out, so to speak, res- doing resistance training, which I think is terrific.

   26. CMDr. Casey Means42:06

       Terrific, yeah.

   27. AHAndrew Huberman42:06

       Used to be such, you know, eh, such, so restricted to niche subculture stuff, like bodybuilding, preseason football, military, et cetera, and now it's, uh, more ubiquitous, uh, for everybody. Men, women, young, old. That's terrific. Same thing with things like yoga and cardiovascular training. I mean, I, eh, like to study the history of exercise culture, and it wasn't but in the '60s when, you know, jogging was considered kind of like, whoa, that's like a really esoteric-

   28. CMDr. Casey Means42:32

       Yeah.

   29. AHAndrew Huberman42:32

       ... niche culture thing, so lot's changed. Um, I love the prescriptives you gave because it's just very straightforward. A couple of short walks. Um, it just makes so much sense.

   30. CMDr. Casey Means42:41

       Mm-hmm.
9. 44:25 – 51:18

   Tools: Exercises to Improve Mitochondrial Capacity; Desk Treadmill

   1. AHAndrew Huberman44:25

      Um, okay, so that, uh, touches on walking. Uh, you did mention higher intensity exercise, so let's-

   2. CMDr. Casey Means44:30

      Mm-hmm.

   3. AHAndrew Huberman44:31

      ... um, keep it within the cardiovascular realm for now. So, um, getting heart rate way, way up. You know, getting, breathing hard for-

   4. CMDr. Casey Means44:40

      Mm-hmm.

   5. AHAndrew Huberman44:40

      ... you know, some minutes, um, each week, maybe a couple times per week. Um, seems that's a good way to increase mitochondrial function and mitochondrial number.

   6. CMDr. Casey Means44:49

      Mm-hmm.

   7. AHAndrew Huberman44:49

      Is that right?

   8. CMDr. Casey Means44:51

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

   9. AHAndrew Huberman47:32

      Terrific. What, what are your thoughts on, um, under-the-desk treadmilling? I, I don't own one of these, but... and I try and get walks and I definitely do my three resistance training exerc- uh, 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.

   10. CMDr. Casey Means47:50

       Yeah.

   11. AHAndrew Huberman47:50

       But I like to do a long hike once on the weekend, a 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, um, you know, the feeling that my, uh, heart is gonna jump-

   12. CMDr. Casey Means48:04

       (laughs)

   13. AHAndrew Huberman48:04

       ... out of my chest and I'm gonna ge- gonna die from gasp of air. But luckily, thus far, I haven't died. Nonetheless, um, the total time commitment isn't that great, but I find that I'm at a desk a lot.

   14. CMDr. Casey Means48:15

       Yeah.

   15. AHAndrew Huberman48:15

       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.

   16. CMDr. Casey Means48:21

       I'm a massive fan of under-treadmill desks because genuinely I believe that if we, if we move more of our daily activities that we're doing seated indoors to outdoors moving, it would, it would ra- it would radically change the health of the United States, with real physiology underneath it. So, there's actually been research on under-desk standing desks that is pretty interesting. Small studies, but they, you know, took a handful of people, I think it was around 10 (laughs) , um, in a workplace environment, and they had them use under-desk treadmills for two and a half hours, uh, per day during the workday, so not a lot, at very slow speeds, for, uh, two weeks. And people lost on average 2.6 pounds of fat and put on 2.2 pounds of lean mass-

   17. AHAndrew Huberman49:10

       Wild.

   18. CMDr. Casey Means49:11

       ... in a very short period of time. The study makes a-... w- somewhat wild claim that if this were extrapolated to a year, we anticipate that we could see a loss of 44 to 66 pounds, which-

   19. AHAndrew Huberman49:25

       Assuming it's, assuming it's linear progression.

   20. CMDr. Casey Means49:27

       Exactly. (laughs)

   21. AHAndrew Huberman49:27

       Which is not, which is not the case, folks, right? Interesting.

   22. CMDr. Casey Means49:29

       But I, that's why I'm saying, it was, it was a pretty-

   23. AHAndrew Huberman49:31

       Yeah.

   24. CMDr. Casey Means49:31

       But that was there in the discussion. And but I think that short period is quite interesting. Um, 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 s-" But I'll start, and just see how it feels, and then an hour goes by, and I've forgotten I'm even on it.

   25. AHAndrew Huberman50:06

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

   26. CMDr. Casey Means50:12

       I am putting it at such a slow speed. I think I'm usually walking at like one mile per hour. I mean, it's very, very glacially slow. I do put my Oura Ring on my second toe when I do this, because otherwise, it doesn't count my steps.

   27. AHAndrew Huberman50:25

       (laughs)

   28. CMDr. Casey Means50:25

       Because if your hands are at your desk, they, uh, they-

   29. AHAndrew Huberman50:28

       Oh, right.

   30. CMDr. Casey Means50:28

       It won't count your steps.
10. 51:18 – 57:14

    Soleus Push-Ups & Fidgeting, Non-Exercise Activity Thermogenesis (NEAT)

    1. CMDr. Casey Means51:18

    2. AHAndrew Huberman51:18

       Terrific. Yeah, I'm a, I'm a fan of getting walks when I can. I also, one of your thoughts on, there was a study, I'm not sure if you're familiar with it, um, published out of the University of Houston, where they looked at what they called soleus push-ups.

    3. CMDr. Casey Means51:31

       (laughs) Yes.

    4. AHAndrew Huberman51:32

       Um, which, uh, all the gym-goers-

    5. CMDr. Casey Means51:34

       (laughs)

    6. AHAndrew Huberman51:34

       ... are going to roll their eyes. Um, imagine sitting down and, uh, raise, uh, pressing your toe against the ground and raising your heel, so kind of like seated calf raise, but no weight.

    7. CMDr. Casey Means51:44

       Right.

    8. AHAndrew Huberman51:45

       Right under the desk. And this study had some remarkable claims and conclusions, um, which included, as I recall, that the activation of this muscle, the soleus, which makes up about 1% of the body's total musculature, um, involved, uh, caused rather, a disproportionate use of blood glucose.

    9. CMDr. Casey Means52:05

       Yeah.

    10. AHAndrew Huberman52:05

        So, it mobilized blood glucose in a good way.

    11. CMDr. Casey Means52:07

        Yeah.

    12. AHAndrew Huberman52:08

        Um, 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-

    13. CMDr. Casey Means52:24

        (laughs)

    14. AHAndrew Huberman52:25

        ... and a few other podcasts, and it was interesting to see the sort of attacks that I got. Like, people really didn't like the idea, um, that this was any different than so-called NEAT, non-exercise, um, activated thermogenesis. So, it's known that people that fidget a lot, or, or move around a lot burn a lot of calories. This actually goes back to some really beautiful work, um, uh, several decades or more ago from Rothwell and Stock, who talked about like the fact that animals and people who fidget a lot-

    15. CMDr. Casey Means52:50

        Mm-hmm.

    16. AHAndrew Huberman52:50

        ... burn a lot of energy.

    17. CMDr. Casey Means52:51

        Amazing, yeah.

    18. AHAndrew Huberman52:52

        They tend to be thinner. They tend to have lower adipose tissue stores. Um, and it's because they're just burning a lot more calories. And this is actually what, um, people who suffer from anorexia, which is, by the way, the most deadly of the psychiatric conditions, so it's, um-

    19. CMDr. Casey Means53:05

        Mm-hmm.

    20. AHAndrew Huberman53:05

        We're talking about true anorexia, are encouraged not to do.

    21. CMDr. Casey Means53:09

        Yeah.

    22. AHAndrew Huberman53:09

        Because, um, 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, um, bouncing the knee, that thing that drives everybody crazy, if you're not the one doing it-

    23. CMDr. Casey Means53:23

        (laughs)

    24. AHAndrew Huberman53:23

        ... um, soleus push-ups. Uh, what are your thoughts about this and 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.

    25. CMDr. Casey Means53:35

        That's right, contracting muscles. It's medicine. And I, I find the concept of NEAT just endlessly fascinating. You know, 'cause we, 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, a prime potential intervention for the obesity epidemic, and it all goes back to the cell. Like, it's, uh, 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. Um, and I think that it- it just, it is funny though that like we have these acronyms for basically like this is just the way life was 100 years ago. If you look at like the 1800s, almost 100% of Americans lived on a farm, basically, like pre-industrialization, pre-urbanization. Most Americans, not 100% but close, lived, they grew some of their own food, they lived either on a farm or had a large garden. Now, that number is less than 1%. So, like movement was just built into everything we did. And, 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 farmer's markets and sort of like, you know, outdoor open-air markets. Then it's supermarkets. Then it's, you know, now it's literally buying food online with the click of the button, and now some people aren't even doing that. They're ordering the food delivered to them with Uber Eats. So, at every level, we've taken away movement from everyday life, and now we have sort of an acronym to like bring it back in. But really, it's about just, you know, giving the body stimulus- stimuli that the cells have been entrained to expect throughout all of human history, and building it 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 the minutiae, but, like, at the end of the day, all the simple habits that we know are healthy, like, fundamentally improve cellular biology. And, like, some of these things, like the knee, like the walking, like, it's emblematic of the fact that, um, some of the simplest solutions are the ones that are by far the most effective. And I think, I think the biggest misconception in healthcare right now is that the way out, and the way to get really back to, to true incredible health is complicated. Like, it's, it's really not that complicated. We've, 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 'cause they all positively impact the mitochondria, they positively impact oxidative stress, they positively impact inflammation.

    26. AHAndrew Huberman57:05

        Mm-hmm.

    27. CMDr. Casey Means57:05

        So, yeah.

    28. AHAndrew Huberman57:06

        I love it. I love simple solutions that hit multiple cellular pathways-

    29. CMDr. Casey Means57:11

        Yes. (laughs)

    30. AHAndrew Huberman57:11

        ... that can make everybody healthier.

11. 57:14 – 58:21

    Sponsor: InsideTracker

    1. AHAndrew Huberman57:14

       I'd like to just take a quick break and acknowledge one of our sponsors, InsideTracker. InsideTracker is a personalized nutrition platform that analyzes data from your blood and DNA to help you better understand your body and help you reach your health goals. Now, I've long been a believer in getting regular blood work done, for the simple reason that many of the factors that impact our immediate and long-term health can only be addressed, that is, can only be measured with a quality blood test. Now, one issue with many blood tests out there is that you get information back about lipid levels, hormone levels, metabolic factors, et cetera, but you don't know what to do with that information. With InsideTracker, they make it very easy to understand your levels and what they mean, and specific actionable items that you can undertake in order to bring those levels into the ranges that are optimal for you. InsideTracker also offers InsideTracker Pro, which enables coaches and health professionals to provide premium and personalized services by leveraging InsideTracker's analysis and recommendations with their clients. If you'd like to try InsideTracker, you can go to insidetracker.com/huberman, and you'll get 20% off any of InsideTracker's plans. Again, that's insidetracker.com/huberman.

12. 58:21 – 1:11:16

    Tool: Blood Test Biomarkers, Vital Signs & Mitochondrial Function

    1. AHAndrew Huberman58:22

       I'd like to talk about assessment.

    2. CMDr. Casey Means58:24

       Yes.

    3. AHAndrew Huberman58:24

       Blood tests in particular. Um, I remember in college, I was just very curious about blood testing, and I had read a little bit about it, but it was really hard to access. Um, I actually went to the student health center and said, "You know, can I just get, um, like, my lipids measured, some hormone stuff measured?" I was in great health, I just wanted to do that, and they're like, "No." Like, "What's the issue?" You know? "Why, why would you do that?" Now it's very easy to find places that will do blood tests, but there is some cost often, um, 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, um, with continuous monitoring and with, um, snapshot monitoring. So, um, let's talk about blood tests. Wh- what, what do you think are, um, the three to five things that basically everybody, if they can, should know about what's circulating in their blood? I'm, I'm imagining LDL, HDL, this kind of thing. I guess ApoB is a big w- uh, favorite of our, our friend-

    4. CMDr. Casey Means59:28

       Mm-hmm. (laughs)

    5. AHAndrew Huberman59:28

       ... Peter Attia. Um, fasting blood glucose, continuous blood glucose-

    6. CMDr. Casey Means59:33

       Yeah.

    7. AHAndrew Huberman59:33

       ... you know, 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, 'cause my, my point here is not to answer the question for you-

    8. CMDr. Casey Means59:41

       (laughs)

    9. AHAndrew Huberman59:42

       ... but that's what comes to mind.

    10. CMDr. Casey Means59:43

        You got, you know, you got the big ones. So this, this is key, is that every single person listening, I hope, after this episode, will go to their health record or send their doctor a message and at least get the following test. And the first seven that I'll mention are very basic, and people might take umbrage to them, because obv- obviously there's a lot of debate about, like, what's everyone's favorite lab test. But I think about it as, like, what are the basics that everyone should know, and then what's, like, the next tier up that are easy to access and are cheap that'll give you a lot more richness, but which you still might have to kind of fight your doctor for? So the first few that you will not have to fight your doctor for, and are often free on an annual physical, and literally define metabolic syndrome are fasting glucose, fasting triglycerides, HDL cholesterol, hemoglobin A1C, total cholesterol, waist circumference, and blood pressure.

    11. AHAndrew Huberman1:00:37

        Okay, sorry, b- I hate to interrupt-

    12. CMDr. Casey Means1:00:39

        Oh, y-

    13. AHAndrew Huberman1:00:40

        ... and my audience hates it even more, but I'm going to just, could you just explain what each of those-

    14. CMDr. Casey Means1:00:44

        Yep.

    15. AHAndrew Huberman1:00:44

        ... is and what it, what it corresponds to?

    16. CMDr. Casey Means1:00:46

        Yes.

    17. AHAndrew Huberman1:00:47

        Great. Thank you.

    18. CMDr. Casey Means1:00:47

        And, 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, it's two reasons. One is that the two studies over the past five years that have shown us in large populations that the vast majority of American adults are metabolically dysfunctional use those biomarkers. So I think because of that, it's important to know them, and the two studies that I'm referring to are one from UNC in 2018, which showed that based on those biomarkers, 88% of American adults are s- have suboptimal metabolism. And then a follow-up study from the Journal of the American College of Cardiology from last year showed that that number has gone to 93.2% of American adults are suboptimal in their metabolism. And these are the metrics that they used, and they're very basic. If you had to pay out of pocket, they would be less than $100. So, let's talk through them. Why they're great-... is because together, they give you kind of like a tapestry of what's actually happening inside the cell if you choose to look at them that way, if you read the tea leaves of them.

    19. AHAndrew Huberman1:01:50

        Mm-hmm.

    20. CMDr. Casey Means1:01:51

        Our... The doctors often, if they see all these lab tests, it'll be in an electronic health record. We've all been through this experiment, 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 it down. Oh, your blood pressure's high, we need to bring it down." But what I'm inviting people to do is understand a little bit about each test and then read the tea leaves of what it's telling us about our mitochondria. So, let's start with fasting glucose. So, fasting glucose, when you look at these studies that I'm referring to, they call optimal less than 100. So, to define whether you were in that 88 or 93%, you had to essentially be in the, their, their optimal range for all biomarkers, not on medication. So, I'll quickly run through what their ranges were. My ranges for optimal are tighter than these but, fasting glucose less than 100, triglycerides less than 150, HDL above 40 for men or 50 for women, hemoglobin A1C less than 5.7%, total cholesterol to HDL ratio less than 3.5 to 1, waist circumference less than 35 inches for women or 40 inches for men, and blood pressure less than 120 over 80. If those things were in those ranges and you weren't on medication for blood sugar or, or blood pressure or whatnot, you were considered optimally metabolically healthy. That's now 6.8% of Americans. (laughs) Um, all of these biomarkers are easy to change in one to two months, I would say, with simple lifestyle habits.

    21. AHAndrew Huberman1:03:32

        Could you remind us what hemoglobin A1C is? I think most people are familiar with HDL cholesterol being the, quote unquote, "good" cholesterol-

    22. CMDr. Casey Means1:03:38

        Right.

    23. AHAndrew Huberman1:03:38

        ... and LDL being the "bad" cholesterol. And as I say that, I know I'm going to get dogpiled. Um.

    24. CMDr. Casey Means1:03:43

        Yeah. Oh, totally, yeah.

    25. AHAndrew Huberman1:03:45

        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 I adhere to.

    26. CMDr. Casey Means1:03:50

        (laughs)

    27. AHAndrew Huberman1:03:51

        But I am sure that most people think of them that way.

    28. CMDr. Casey Means1:03:53

        Yep.

    29. AHAndrew Huberman1:03:54

        Um, so just as a-

    30. CMDr. Casey Means1:03:55

        Yeah.
13. 1:11:16 – 1:16:46

    Navigate Medical System & Blood Tests, Consumer Lab Testing

    1. AHAndrew Huberman1:11:16

       Um, in terms of getting a basic blood test, as, uh, you're a physician, what's the secret code? Um, I'll give away one that, um, a former guest who's also an MD shared, which is oftentimes if you ask your physician for a blood test, they will say, "Well, unless there's a particular need or you're, um, 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 stethoscopes. Um, uh, I'm willing to stand my ground. Um, if you want a blood test, it's often useful to mention that there's been some marked shift. Um, you want to be honest, right? But some marked shift in sleep, in lifestyle, in how you feel, standing up, sitting down. I'm not trying to l- you know, lace people's minds with ideas to, to, uh, create narratives here, but, um, oftentimes where physicians are resistant, they'll be more amenable if they understand that, "Hey, like, something's changing," and the patient's saying something's changing. It actually would be irresponsible of them to not give the blood test. So, there you go. Um, bring it on, MDs. So, yeah.

    2. CMDr. Casey Means1:12:22

       Yeah, truly. And I think the nice thing about these, again, very basic tests, and there are so many other tests that I talk about in my book and that you've talked about on your podcast, ApoB, uric acid, fasting insulin, HOMA-IR, hsCRP, liver function test, GGT, all these other tests that are great that can really tell us more about mitochondrial dysfunction, oxidative stress, chronic inflammation. But the ones I'm mentioning are the ones that you will not have to fight with your doctor about. Like-

    3. AHAndrew Huberman1:12:47

       Oh, good.

    4. CMDr. Casey Means1:12:48

       ... the, 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, if they're creeping up or if s- many of them are a little bit high, like, we need to focus all of our energy on improving mitochondrial capacity basically, and, 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 (laughs) , I give scripts to literally talk to your doctor with-

    5. AHAndrew Huberman1:13:21

       Oh, fantastic.

    6. CMDr. Casey Means1:13:21

       ... because you are going to get pushback often. If you ask for a fasting insulin, I would say probably, I mean, even though doctors are waking up a little bit, like, maybe 85% of people are 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, am- amazing companies doing direct con- to consumer lab testing so you can basically avoid the hassle. And some of them are very affordable. There's, um... 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 t- ... And then they do interpretations. Um, InsideTracker, uh, 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, a crumb of information about their health. And it's, it's, it's w- we should probably be testing these, I would say, th- three to four times a year. Um, 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 2 or eccentric?" It's like there's so much noise. And the beauty with having a plan for understanding your biomarkers regularly is that you can cut through all the noise, try a strategy, see where you stand, re- retest in a few months, and see if you're moving in the right direction. You don't ha-

    7. AHAndrew Huberman1:15:04

       A bit like a scientist.

    8. CMDr. Casey Means1:15:05

       You don't have to trust your doctor.

    9. AHAndrew Huberman1:15:06

       Yeah.

    10. CMDr. Casey Means1:15:06

        You don't have to trust me. You don't have to trust anyone. You can literally trust your own labs. And I, I, I say to people, like, "If your labs are optimal," and the range that I just mentioned are not optimal, like, we, we- you want to actually get to better than all of those if you want to be opt- ... If your, if your 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, and, and exercise and your lifestyle, because that is showing that your cells are fundamentally working properly. So, I think that's just a really empowering message that... And 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? 'Cause it's like people can just say, like, "I trust my strategy. I know I'm doing what's right for me 'cause, like, look at all my biomarkers and I feel great," you know? So...

    11. AHAndrew Huberman1:16:05

        Yeah. What used to be the before and after, um, you know, pre-diet exercise, post-diet exercise, um, photos on social media are now starting to also include numbers, which is kind of interesting. I mean, obviously, these aren't randomized controlled trials, but it's cool to see people posting their numbers-

    12. CMDr. Casey Means1:16:23

        Yeah.

    13. AHAndrew Huberman1:16:23

        ... of things that are not just related to aesthetics, but are, um ... or body weight, but are related to he- health metrics.

    14. CMDr. Casey Means1:16:31

        Yeah.

    15. AHAndrew Huberman1:16:32

        Uh, it's, it's, it's fun. I think it, it speaks to, um, a more scientific, or at least a more quantitative approach to things, and I think it's inspiring for people. Um, thanks for putting those scripts in the book-

    16. CMDr. Casey Means1:16:43

        (laughs)

    17. AHAndrew Huberman1:16:43

        ... that people can refer to. Um, let's

14. 1:16:46 – 1:21:58

    Tool: Environmental Factors; Food, Life as a Process

    1. AHAndrew Huberman1:16:46

       say that, um, 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's a little high, um, maybe a few other things are okay. So, I'm kind of in the m- you know, not in the red zone, but I'm in the, like, "Mm, I should probably pay attention to these things."

    2. CMDr. Casey Means1:17:05

       Yeah.

    3. AHAndrew Huberman1:17:06

       What are some of the things that one can do in order to try and move those needles in the right direction? Um, I know we talked about walking and movement before. What are a few others? And maybe we could start to touch into nutrition a little bit-

    4. CMDr. Casey Means1:17:17

       Mm-hmm.

    5. AHAndrew Huberman1:17:17

       ... and then we'll pivot to, um, insulin and blood glucose.

    6. CMDr. Casey Means1:17:20

       Mm-hmm. 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, um, and that are- we know based on the science are impacting our mitochondrial and metabolic health is the food, the sleep, the movement, the emotional health, the toxins, our relationship with light, and our relationship with temperature. And your journey to optimal metabolic health might be totally different from mine, 'cause 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 thi- those are the things in our environment that we need to, to basically improve to ha- 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 100% molecularly made from food. And-

    7. AHAndrew Huberman1:18:51

       That's so wild.

    8. CMDr. Casey Means1:18:52

       It's so wild.

    9. AHAndrew Huberman1:18:53

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

    10. CMDr. Casey Means1:18:56

        Like, babies are-

    11. AHAndrew Huberman1:18:57

        You know, it's like-

    12. CMDr. Casey Means1:18:57

        ... 3D printed from food, basically, inside a, a woman's bo- it's, 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 'cause 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."

    13. AHAndrew Huberman1:19:24

        I love that.

    14. CMDr. Casey Means1:19:24

        And then the W- (laughs) yeah.

    15. AHAndrew Huberman1:19:25

        And, um ... No, I'm sorry to interrupt. I'm just... I, I always, you know, wish that if people could understand that, um, with biology and health, understanding the nouns and the names-

    16. CMDr. Casey Means1:19:36

        Yeah.

    17. AHAndrew Huberman1:19:36

        ... is important, but it's verbs.

    18. CMDr. Casey Means1:19:38

        Yeah.

    19. AHAndrew Huberman1:19:38

        It's verbs, verbs, verbs.

    20. CMDr. Casey Means1:19:40

        Yes.

    21. AHAndrew Huberman1:19:40

        If you understand that things are procesees or processeeS depending on, uh, who you are-

    22. CMDr. Casey Means1:19:45

        Mm-hmm.

    23. AHAndrew Huberman1:19:45

        ... and where you live in the world-

    24. CMDr. Casey Means1:19:46

        (laughs)

    25. AHAndrew Huberman1:19:47

        It all becomes so much more tractable.

    26. CMDr. Casey Means1:19:49

        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, (laughs) 'cause I'm just, I'm Casey and that's who I am and I have this disease, you know. And, and I think so much in our language, actually, of healthcare, uh, both our Western sort of despiritualized nature, like, we don't really have a lot of curiosity with, with process, but even, like, the ideas, the way we talk about disease. "I have diabetes," you know, and I, I, uh, and, and we don't even talk about diabetes cures, which now a lot of people are curing their diabetes. We call it remission. Like it's this thing that's a part of you. And I think, I just love this idea of, like, we're evolving every day and food is so important because again, we take in 70 metric tons of food in a lifetime, two to three pounds per day, one 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, our conception of food, I think, is very limited. Um, food is the molecular building blocks of the body. It is the cell signaling functional molecules that tell our cells what to do. They act as transcription factors, epigenetic modifiers, um, cell signaling pathway intermediates, and it's also, of course, the substrate to change what the microbiome does and the composition of the bio- microbiome, which is basically a pharmacy inside our bodies to create different molecules that can affect our health. So food is, certainly a calorie's a calorie from the concept of thermodynamics, but from the concept of molecular information, it has three massively important parts that are unavoidable for creating cellular health. So I would just say that that is the pillar that we can dril- uh, be happy to drill into of, like, what do we really do to, you know, build, build as much metabolic health as possible?

    27. AHAndrew Huberman1:21:57

        Yeah,

15. 1:21:58 – 1:32:03

    Tool: Ultra-Processed vs. Real Food, Obesity, Soil & Micronutrients

    1. AHAndrew Huberman1:21:58

       I want to focus now, if you're willing, on food, not just macronutrients-

    2. CMDr. Casey Means1:22:03

       Yeah.

    3. AHAndrew Huberman1:22:03

       ... proteins, fats, and carbohydrates, not just calories, although that as well, but things like timing, things like fasting.

Episode duration: 2:56:26