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

28:37And 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 diacylglycerol.

29:13And I'm also going to block the cell from taking any more substrates because I can't do anything with them. That is fundamentally a root of insulin resistance. So the body says, okay, we're going to block the ability of the insulin receptor to transduce its intracellular signaling pathway. We're going to block it. And when that insulin binds, we're not actually going to allow for glucose to come in. So essentially insulin resistance is the cell compensating for the mitochondria being broken and telling the insulin receptor that it's not going to be functional. And so you don't get the glute receptors on the cell membrane to allow the glucose to come in.

29:50So that's insulin resistance. Again, we talk about that as the problem. But the problem is actually inside the cell leading to that. So that's why just giving someone insulin isn't necessarily the answer. We have to increase mitochondrial capacity to let the flow happen through it to energy, which then trickles up into relieving a lot of these problems. So to answer your question, what we really want to do to increase our metabolic capacity from a first principles perspective, it's we need to make more mitochondria. We need to get each mitochondria to be more functional. and we need to have each more functional mitochondria processing more energy substrates.

30:32It's really that simple. And the beauty is we can do all of those things. If you actually break down what those three things mean, it means promoting mitophagy, the recycling of old mitochondria to new mitochondria. It means promoting mitochondrial biogenesis. It means increasing the oxidative capacity of our individual mitochondria. It means improving mitochondrial fusion, which is actually when mitochondria come together to form long chains of mitochondria that are more efficient. So there's like a lot of technicality to like what it means to print more mitochondria, have them each be more efficient, and have each one do more work.

31:09But 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 high intensity interval exercise. There's compounds like urolithin A that promote mitophagy. 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. But first principles, it's how do we get more of these working better, doing more work every day?

31:49And then we think about, you look at the data on walking, and it's like people who walk more than 7 ,000 steps a day have a 50 % to 65 % lower chance of dying in 10-year follow-ups. And it's like, yeah, because walking is literally a glucose disposal signal. So you're just simply asking. It's not a great biogenesis signal. It's not a great mitophagy signal, but it's a great disposal. So if you're doing lifestyle habits that do one of those three things, which we can, of course, go into more, you're improving the cell's capacity to do that conversion process better. I'd like to take a quick break and acknowledge one of our sponsors, Athletic Greens.

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33:38There's a lot of great science and a lot of great stuff related to testing and assessment of one's metabolic health that we should get into and will get into. But since we touched on lifestyle and because we've been talking about the sort of dysfunctional dark side for a bit, maybe we could just touch on some of the lifestyle factors that you just mentioned. Because I do think it's important that people really start to feel into their sense of agency. And here we're talking about things that are relatively low time investment, certainly don't have much financial cost in the sense that they could be done in gyms and with fancy equipment, but they don't require that.

34:16Again, I want to point out that these are not like strict prescriptives. But if you had a magic wand and because you are interested in the health of humans, let's talk about a few of these things that can improve glucose disposal and mitochondrial function, mitophagy, the removal of dead or dysfunctional mitochondria so they can be replaced. Let's talk about the walking one first. 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.

34:52You'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, I mean, at least three. I would say aiming for more than that is good, though. So to sort of just give a sense of the picture of walking, if walking were a pill, it would be the most impactful pill we've ever had in all of modern medicine. There was a paper in JAMA, 6 ,300 participants followed for 10 to 11 years. And the people who simply walked 7 ,000 steps per day compared to less than that had an up to 70 % lower risk of all-cause mortality in the follow-up period.

35:40So not causality, but it's pretty incredible. They've done follow-up research with slightly different numbers showing, again, though, like many thousands of people in the study followed for about 10 years, 8 ,000 to 12 ,000 steps per day was associated with 50 % to 65 % lower all-cause mortality. And this has been played out in many studies showing about a 50 % reduction in Alzheimer's, dementia, obesity, type 2 diabetes, depression, cancer, gastric reflux, just all across the board. And I think the key thing is that it's not about the steps. It's about the fact that muscle contraction is medicine.

36:22When we contract our muscles, even in a very low-grade way, like walking or doing a couple 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.

37:07Maybe they're exercising at the end of the day or the beginning of the day. Maybe they're not. that person is stimulating glucose channels to be at the membrane all day. Now let's take another person who works out really hard for one hour in the beginning or the end of the day. They feel great about it. They've checked that off their box, but they're sitting the entire rest of the day. Yes, they have gotten the benefits from the exercise, but for a lot of that day, those glucose channels are inside the cell, not doing the work they could be doing. So I think about these little teeny short walking breaks or push-up breaks or air squat breaks every 30 minutes or so throughout the day as me essentially inside the cell pushing the glucose channels, the cell membrane to make them constitutively active.

37:52It'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 too 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, either 20 minutes before either 20 minutes after or two to three minutes, every 30 minutes, all added up to 60 minutes of walking or light jogging a day.

38:33I'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 these channels of the membrane to take up the substrate, use the substrate.

39:10So this is not 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.

39:56Or if that's tough, you really need to sit at your desk all day, then every 30 minutes, taking two minutes to do some just light movement, flex those muscles, get the glucose channels of the membrane, get the mitochondria active. So – and I think another fascinating stat is like our gym memberships in the U.S. have doubled since the year 2000 and obesity has gone up in the same period. So there's some mismatch between our obsession with exercise and our actual outcomes that we're seeing. And I think it's that we have not actually rebuilt constitutive movement into our daily lives. Very interesting because I think a lot of people are now working out, so to speak, doing resistance training, which I think is terrific.

40:40Terrific, yeah. used to be so restricted to niche subculture stuff like bodybuilding, pre-season football, military, et cetera. And now it's more ubiquitous for everybody, men, women, young, old, that's terrific. Same thing with things like yoga and cardiovascular training. I mean, I like to study the history of exercise culture and it wasn't, but in the 60s when 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.

41:16And I love the visual, and I hope people will really hold it in mind, so I'll reiterate it. The translocation of these energy utilization stores, vesicles as you call them, these little packets, from the center of the cell out to the cell surface where then they can be involved in metabolic processes and the utilization of energy. in ways that otherwise they wouldn't. And glucose disposal being a big part of this. So I have heard that a short walk after a meal will reduce blood glucose in a way that's really dramatic. Huge amount, 30, 35 % just taking a walk around the block after a meal. That's definitely a prescription I think everyone should do because the research is so strong on it is that building in simply a 10 minute walk around the block or a dance party in the kitchen, moving your muscles for 10 minutes after a meal can drastically reduce your glucose response because you're just bringing all those channels to the membrane.

42:12You'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 if it's after a meal. So highly recommend that. And the levels data and clinical data has shown that out time and time again. Whenever I go to a city like New York, when I am forced to walk more, I always just feel so much better. We also know that the optic flow that one experiences with walking has some interesting effects on the limbic pathways and quieting of some of the anxiety and stress-related pathways. This links up with things like EMDR, although there are factors that are separate from EMDR.

42:47Basically, moving through space, not outer space, but walking through space with optic flow, has a certain anxiety reduction function in the brain, which there are 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 type of exercise.

43:28We'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.

44:09When we think about resistance training, it's like that's like muscle hypertrophy. We're going to be creating more muscle cells and we need more mitochondria for those. So each one has kind of a different impact. And I think this is where, honestly, I think the regular guidelines that we have even by our government, you know, actually make a lot of sense. It's like work every major muscle group three times a week in a resistance type training and then work to get 75 to 150 minutes of moderate strenuous activity. So 75 minutes of strenuous activity or 150 minutes per week of moderate activity. So that actually makes a lot of sense.

44:4480 % of Americans are not meeting those very basic guidelines. And 20 % of Americans don't get any physical activity really at all. Activity for the average American is 3 ,000 to 4 ,000 steps per day, which is less than two miles. So we are not even close to even meeting the basic recommendations that are out there. But I think those are pretty reasonable. Resistance training, two to three times a week, most major muscle groups, and working to get the heart rate up moderate level for 150 minutes a week or strenuous for 75 minutes a week. Those are going together to be potent stimuli for biogenesis, mitophagy, mitochondrial fusion, for increasing antioxidant enzymes that are going to protect the mitochondria from that oxidative stress.

45:35And 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 7 ,000 steps per day based on what the data is showing, which honestly would probably take less than an hour total to do if you break it up throughout the day. It's just a few minutes a day. So that right there are going to be like a big multifaceted set of signals for increasing mitochondrial capacity in different ways. Terrific. What are your thoughts on under the desk treadmilling? I don't own one of these, and I try and get walks, and I definitely do my three resistance training sessions per week, different muscle groups on different days.

46:20So 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, 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 the feeling that my heart is going to jump out of my chest and I'm going to die from gasp me of air. But luckily thus far, I haven't died. Nonetheless, the total time commitment isn't that great, but I find that I'm at a desk a lot and I have a standing desk. Is it wise to get a treadmill, to treadmill under the desk?

46:53seems like it would be one of the best things one could do. I'm a massive fan of under treadmill desks because genuinely I believe that if we move more of our daily activities that we're doing seated indoors to outdoors moving, 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 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 workday.

47:33So 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 progression. Exactly. Which is not the case, folks. But that's why I'm saying it was a pretty – but that was there in the discussion. But I think that short period is quite interesting. So 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 underdesk treadmills, I think for anyone who's a knowledge worker, it's a good thing to have at your house.

48:26And the way I use it is like I basically just force myself to start my day on the treadmill desk. And I say to myself, if I don't like it after five minutes, I'll sit down if I need to sit. But I'll start and just see how it feels. And then an hour goes by and I've forgotten I'm even on it. Is that right? So you're able to work without thinking about having to treadmill. mil? 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 aura ring on my second toe when I do this, because otherwise it doesn't count my steps.

48:59Because if your hands are at your desk, they, they won't count your steps. Because the aura rings measuring hand. Accelerometry. Yeah. But it, it, it's incredible how even at a 1.0, one mile per hour speed after two to three hours, you're easily going to get six, seven, 8 ,000 steps and then throw in a couple couple other short walks throughout the day and you're getting there easily. So it's just a great way to build back in what modernity took away. And that unfortunately is unavoidable, that regular movement for good physiology. So I'm a big fan of them. And the data suggests that for a couple hours a day, they can actually have an impact on body composition, which I think is a great, easy, inexpensive thing for people to do.

49:45But if you don't want to buy one, just set those timers and build in the walks throughout the day outside. Terrific. Yeah. I'm a fan of getting walks when I can. I also, I wonder your thoughts on, there was a study, I'm not sure if you're familiar with it, published out of the University of Houston, where they looked at what they called soleus pushups, which all the gym goers are going to roll their eyes. Imagine sitting down and pressing your toe against the ground and raising your heel. So kind of like seated calf raise, but no weight right under the desk. And this study had some remarkable claims and conclusions, which included, as I recall, that the activation of this muscle, the soleus, which makes up about 1 % of the body's total musculature involved, caused rather a disproportionate use of blood glucose.

50:39So 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 the sort of attacks that I got. Like people really didn't like the idea that this was any different than so-called NEAT, non-exercise activated thermogenesis. So it's known that people that fidget a lot or move around a lot burn a lot of calories.

51:14This actually goes back to some really beautiful work several decades or more ago from Rothwell and Stock who talked about like the fact that animals and people who fidget a lot burn a lot of energy. They tend to be thinner. They tend to have lower adipose tissue stores. And it's because they're just burning a lot more calories. And this is actually what people who suffer from anorexia, which is, by the way, the most deadly of the psychiatric conditions. So it's talking about true anorexia are encouraged not to do because they either do it spontaneously or they learn that it's a very efficient way to burn calories.

51:48And 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 um soleus push-ups uh 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 i find the concept of neat just endlessly fascinating you know because 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 a 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 just it is funny though that like we have these acronyms for basically like this is just the way life was 100 years ago.

52:51If you look at like the 1800s, almost 100 % of Americans lived on a farm, basically like pre-industrialization, pre-urbanization. Most Americans, not 100%, but close, lived. They grew some of their own food. They lived either on a farm or had a large garden. Now that number is less than 1%. So like movement was just built into everything we did. And you think from there, like, what has happened? Like, we were outside, we were moving, our activities of daily living involved movement. And if you just take the grocery example, then it moved to like, okay, maybe farmers markets and sort of like, you know, outdoor open air markets, then it's supermarkets, then it's, you know, now it's literally buying food online with the click of the button.

53:36And now some people aren't even doing that. They're literally on the food delivered to them with Uber Eats. So at every level, we've taken away movement from everyday life. And now we have sort of an acronym to like bring it back in. But really it's about just, you know, giving the body stimulus stimuli that the cells have been entrained to expect throughout all of human history and building the back into our modern life. So I 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.

54:19Like the way out is pretty simple. Like it's some of these basic things like walking more throughout the day, moving more throughout the day, getting outside, you know, eating clean, unpoisoned food. A lot of these things that have the best data are so simple. And I think it's like really important to just always remember like the game and the industry, it's all about how complex can we make it like specialization, talking about some of the minutia. 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.

55:08And I think, I think the biggest misconception in healthcare right now is that the way out and the way to get really back to true incredible health is complicated. It's really not that complicated. We've got to move more. Throughout the day, that's one of them. On each pillar that we touched on earlier, food, sleep, all of this, when we talk about the simple habits that we know work, the reason they work is because they all positively impact the mitochondria. They positively impact oxidative stress. they positively impact inflammation. So, yeah. I love it. I love simple solutions that hit multiple cellular pathways that can make everybody healthier.

55:48I'd like to talk about assessment, blood tests in particular. I remember in college, I was just very curious about blood testing and I had read a little bit about it, but it was really hard to access. I actually went to the student health center and said, 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, like, what's the issue? You know, why would you do that? Now it's very easy to find places that will do blood tests, but there is some cost often. And nowadays, thanks to your efforts, your innovative and engineering efforts and the efforts of others.

56:26There are ways to measure what's in your blood, blood glucose in particular, with continuous monitoring and with snapshot monitoring. So let's talk about blood tests. What do you think are the three to five things that basically everybody, if they can, should know about what's circulating in their blood? I'm imagining LDL, HDL, this kind of thing. I guess APOB is a big favorite of our friend Peter Atiyah. Yeah. Fasting blood glucose, continuous blood glucose, post-meal, et cetera, just kind of evaluating how exercise, food, et cetera, impacts blood glucose. And then I'll leave the other categories open because my point here is not to answer the question.

57:09That's what comes to mind. You've got the big ones. So this is key, is that every single person listening, I hope, after this episode will go to their health record or send their doctor a message and at least get the following test. And the first seven that I'll mention are very basic and people might take umbrage to them because obviously there's a lot of debate about like what's everyone's favorite lab tests. 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.

57:48So the first few that you will not have to fight your doctor for and are often free on an annual physical and literally define metabolic syndrome are fasting glucose, fasting triglycerides, HDL cholesterol, hemoglobin A1c, total cholesterol, waist circumference, and blood pressure. Okay. Sorry. I hate to interrupt and my audience hates it even more, but I'm going to just, could you just explain what each of those is and what it corresponds to? Yes. Great. Thank you. And I will say, first of all, the reason I'm choosing these, it's not even my own choice, really. It's two reasons. One is that the two studies over the past five years that have shown us in large populations that the vast majority of American adults are metabolically dysfunctional use those biomarkers.

58:30So I think because of that, it's important to know them. And the two studies that I'm referring to are one from UNC in 2018, which showed that based on those biomarkers, 88 % of American adults have suboptimal metabolism. And then a follow-up study from the Journal of the American College of Cardiology from last year show that that number has gone to 93.2 % of American adults are suboptimal in their metabolism. And these are the metrics that they use. And they're very basic. If you had to pay out of pocket, they would be less than$100. So let's talk through them. Why they're great is because together, they give you kind of like a tapestry of what's actually happening inside the cell.

59:13If you choose to look at them that way, if you read the tea leaves of them, the doctors often, if they see all these lab tests, it'll be an electronic health record. We've all been through this 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 is high. We need to bring it down. Oh, your glucose is high. We need to bring it down. Oh, your blood pressure is 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.

59:48So 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 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 if that's seen glucose less than 100, triglycerides less than 150, HDL above 40 for men or 50 for women, hemoglobin 1C less than 5.7%, total cholesterol to HDL ratio less than 3.5 to 1, waist circumference less than 35 inches for women or 40 inches for men, and blood pressure less than 120 over 80.

1:00:38If those things were in those ranges and you weren't on medication for blood sugar or blood pressure or whatnot, you were considered optimally metabolically healthy. That's now 6.8 % of Americans. All of these biomarkers are easy to change in one to two months, I would say, with simple lifestyle habits. Could you remind us what hemoglobin A1C is? I think most people are familiar with HDL cholesterol being the quote unquote good cholesterol and LDL being the bad cholesterol. And as I say that, I know I'm going to get dogpiled. I'm not sure that I adhere to that. I'm not sure I don't adhere to that.

1:01:15I'm not sure about a lot of things. But I am sure that most people think of them that way. So just to stay functional here, we'll frame it that way for now with the caveat that that might not be the whole story, isn't the whole story. But triglycerides, fat in the blood, fatty stuff. But so key to understand about the triglycerides, we don't want to confuse triglycerides with eating more fat. Triglycerides are a storage form of excess carbohydrates in the blood. So this is why it can tell us something about, and I know you and Rob Lustig talked about this at length, but it's - And Lane Norton.

1:01:52And Lane, yeah. 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, but then they also think the macronutrient fat. We just need more words to better parse the reality. In biology, we call the two major groups of people lumpers and splitters. Lumpers like to lump everything together. It oversimplifies and complicates. Splitters like to split everything, give a name for everything, individual name for everything. it complicates. And so there's a middle ground, right? There's a land of reasonable people and nomenclature.

1:02:29And unfortunately, that does not exist on the internet, nor does it exist in any one specific subfield of medicine or science. I mean, so much of the confusion out in the world is because of a lack of adequate language in order to explain. Okay. So the triglycerides are a reflection of excess carbohydrate intake. And how it's helping us with that tapestry of understanding the trifecta of bad energy is that if you think about it, let's just go back to that cell and that poor mitochondria that's being absolutely decimated by our environment and its capacity is low. Okay, so that mitochondria is like I can't process glucose or fatty acids to ATP very well, so I'm going to block their entry into the cell.

1:03:08So now you've got glucose rising in the bloodstream. So, okay, fasting glucose, that was one of our biomarkers. If that's going up, that is a little bit of that tapestry of maybe something's going on inside the cell that's blocking the entry into the cell, so it's rising the bloodstream. Okay, well, where's all that? The body does not want lots of glucose floating around in the bloodstream because it can literally independently cause endothelial dysfunction, which is basically blood vessel problems. It can cause oxidative stress in the bloodstream. It can cause glycation, which is sugar literally just sticking to things.

1:03:39The body doesn't want that glucose high in the bloodstream, so it converts it to triglycerides to be stored in a storage form of energy. That's a key point that I think is helpful to understand is that the body, it's always trying to like kind of keep things in the right range so it'll convert things. So then triglycerides, a picture in your blood of glucose being high and triglycerides being high, is very much should signal to everyone when they look at their labs that there's probably something going on inside the cell that's blocking the cell from being able to use and process. It's a sign of mitochondrial dysfunction and chronic overnutrition.

1:04:18Too much substrate, not enough processing. Glucose is going to go up. Triglycerides are going to go up. And so then if you kind of squint and read the tea leaves, it's like, huh, I think metabolic dysfunction. And what's fascinating is that the travesty in our healthcare system is that a patient might go into the doctor and their fasting glucose is 99, 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.

1:04:52But that's just really problematic because they're on the upper end of normal for both of those. And so really what that would say to me as someone thinking about the mitochondria is like, this person is definitely metabolically dysfunctional. They're on the highest end of normal for both triglycerides and glucose. There's definitely insulin resistance going on here. I would much rather see that glucose at 73 and that triglyceride at 50, which to me would say, oh, this cell's processing through energy. Great. And things are moving through and we're not backing up in the bloodstream. We're not converting to triglycerides.

1:05:29So that's where really optimal ranges get in. So that's glucose and triglycerides. Why, if those are starting to creep up, it's a sign that something is happening metabolically. And then when we look at some of the other biomarkers, so hemoglobin A1C, is really, so that's a marker that's looking at how many of the hemoglobin molecules that are in the red blood cells that carry oxygen, how many of those hemoglobin molecules have sugar stuck to them, and that's glycation. So you're looking at glycated hemoglobin, and you can imagine that if the concentration of glucose is higher over time, more glucose is going to stick to red blood cells, and that's going to create a higher percentage of glycated hemoglobin.

1:06:13So 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. No sugar stuck to them, causing dysfunction. And because blood cells last for about 9 to 120 days, hemoglobin A1C is giving us basically a snapshot of average blood sugar levels over 90 to 120 days. And if that average is higher, again, probably a sign that cells are rejecting glucose from the cell and it's causing a rise in the bloodstream. And then just talking about one other biomarker in that that we talked about, which was blood pressure, people might say, well, how does blood pressure relate to like what's going on inside the cell, you know, in the mitochondria and whatnot?

1:06:58And 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 resistant. So the body is going to churn out more insulin to try and overcome the insulin block to drive the sugar into the cells. So insulin levels rise. Well, insulin is one of the key activators of nitric oxide, which is the molecule in the blood that dilates and relaxes blood vessels. And so when we become insulin resistant and we're not responding to that insulin signal, we end up getting less nitric oxide activity.

1:07:36So 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 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. Again, it sort of comes across to many people as old school, right? But when Atiyah was here, one of the several times he was here, he really pushed on blood pressure as such a key metric, right? I mean, obviously, if blood pressure is high, you're getting less nitric oxide through whatever means here.

1:08:18Vessels and capillaries are constricted. Cells aren't able to use the energy that's coming in. There's excess energy. There's buildup of metabolic waste. There's all this stuff, and now we can start to see the picture that'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, you're a physician. What's the secret code? I'll give away one that a former guest who's also an MD shared, which is oftentimes if you ask your physician for a blood test, they will say, well, unless there's a particular need or you're struggling with something, they won't give it to you.

1:09:04But 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. 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 and lifestyle in how you feel standing up sitting down i'm not trying to you know lace people's minds with ideas to to 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 So bring it on, MDs.

1:09:49Yeah, 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 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.

1:10:26But like how together, if 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 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.

1:10:59So 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 amazing companies doing direct-to-consumer lab testing so you can basically avoid the hassle. And some of them are very affordable. Function Health is a company that's doing 110 biomarkers, including all the key metabolic biomarkers for less than$500, and they'll do it twice a year. So you don't ever have to. And then they do interpretations. Inside Tracker, Next Health, Levels is doing labs. And so there's a lot of this springing up because I think people are sick of fighting with their doctors to get a crumb of information about their health.

1:11:44And we should probably be testing these, I would say, three to four times a year. And the beauty is that I think a lot of what keeps people down in the health world is that they're confused about what to do. There's a lot of noise. There's a lot of different strategies. You know, do I do, you know, paleo, keto, carnivore, vegan, Mediterranean? Do I do HIIT or zone 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. Retest in a few months and see if you're moving in the right direction.

1:12:31Be a scientist. You don't have to trust your doctor. You don't have to trust me. You don't have to trust anyone. You can literally trust your own labs. And I say to people, if your labs are optimal, and the ranges I just mentioned are not optimal, you want to actually get to better than all of those. 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 an exercise in your lifestyle, because that is showing that your cells are fundamentally working properly.

1:13:08So 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, 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.

1:13:45I mean, obviously these aren't randomized controlled trials, but it's cool to see people posting their numbers of things that are not just related to aesthetics, but are, um, or body weight, but are related to health metrics. Yeah. 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.

1:14:24Maybe a few other things are okay. So I'm kind of in the, You know, not in the red zone, but I'm in the like, you should probably pay attention to these things. What are some of the things that one can do in order to try and move those needles in the right direction? I know we talked about walking and movement before. What are a few others? And maybe we could start to touch into nutrition a little bit and then we'll pivot to insulin and blood glucose. I think on the highest level, it's about running through what are the science-based things that we know in our environment can lead to metabolic dysfunction and take honest stock of how those factors are playing out in your life and then choose a few to start moving in a different direction.

1:15:08So the ones that I think are ones that we can really control and that we know based on the science are impacting our mitochondrial metabolic health is the food, the sleep, the movement, the emotional health, the toxins, our relationship with light, and our relationship with temperature. and your journey to optimal metabolic health might be totally different from mine because I might really need to focus on the food and the sleep and the emotional health and you might really need to focus on the toxins and the light and the movement and so it's a lot of it is actually taking stock on where the levers are in your own life where are you crushing it and where is there a lot of room for improvement so step one is knowing like that those are the thing those are the things in our environment that we need to basically improve to give ourselves the best capacity.

1:15:56And then, of course, checking your biomarkers to make sure your interventions are working. But food, I think, is one that is totally unavoidable. Of those pillars, those seven pillars, food is one that most of us are getting wrong and that we really actually have to get right to improve our metabolic health for a lot of reasons. I mean, our bodies are basically 100 % molecularly made from food. That's so wild. It's so wild. Every time I think about that, it kind of 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.

1:16:40So 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 wish that if people could understand that with biology and health, understanding the nouns and the names is important, but it's verbs. It's verbs, verbs, verbs. If you understand that things are processes or processes, depending on who you are and where you live in the world, it all becomes so much more tractable. Yes. And it's so much more hopeful. Because if I'm a process, if you're a process, then every day we're eating, we are changing the process.

1:17:24Whereas if you think you're a thing, then there's no hope. Because 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 de-spiritualized 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 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.

1:18:09And 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 case of today. That's a hopeful message because if we can give the body food, which I think we – again, our conception of food I think is very limited. food is the molecular building blocks of the body. It is the cell signaling functional molecules that tell our cells what to do. They act as transcription factors, epigenetic modifiers, cell signaling pathway intermediates. And it's also, of course, the substrate to change what the microbiome does and the composition of the microbiome, which is basically a pharmacy inside our bodies to create different molecules that can affect our health.

1:18:57So food is certainly a calorie is a calorie from the concept of thermodynamics, but from the concept of molecular information, it has three massively important parts that are unavoidable for creating cellular health. So I would just say that that is the pillar that we can be happy to drill into of like, what do we really do to build as much metabolic health as possible. Yeah. I want to focus now, if you're willing, on food, not just macronutrients, proteins, fats, and carbohydrates, not just calories, although that as well, but things like timing, things like fasting, and micronutrients, which I think is a highly underexplored topic.

1:19:41So 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, there's a lot to explore, however. I can just say for myself, for what it's worth, I'm not very hungry until 11 a.m. 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 single or few ingredient foods I just naturally do so I've been lucky in that way but I know a lot of people like sandwiches processed foods, things that are combinations of ingredients.

1:20:49What 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, or 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?

1:21:29Well, just drilling in on two things you just said there. So one thing you said that was interesting was that you're lucky that you like all of those foods. And then the second thing was, is it just about not getting excess calories? But I think what's interesting about both of those is that I would argue that the reason you like those foods is because you have given your body enough whole, real foods that now everything in your biology, neurobiologically, your reward circuitry, your microbiome, your satiety hormone threshold, all of these are now basically creating a situation in which you like those foods.

1:22:04And 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 our cells 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 met.

1:22:54Unfortunately, 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 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.

1:23:32They don't have the FDA. They don't have the USDA. They don't have any of it. and they have somehow figured out a way to stay at a healthy weight and to not get heart disease. And it's because they're eating real food that meets the needs of their cells. And so I think to just boil that down, the root cause of the problem is that we have a toxic food supply that's no longer filled with the molecular information that our body needs to know to be satiated and to function properly. And so through the complex biology of satiety hormones and neurobiology and microbiome function, we are driven to eat so, so, so much more.

1:24:11So truly the jumping off point for anyone on the quest to better health is to eat as much real unprocessed food from good soil as possible. And of really of any dietary philosophy they want, Truly, I think if someone's eating real unprocessed food from good soil who is plant-based or who is keto, they are going to have such a higher chance of meeting their body's actual fundamental needs. And the good thing about biomarker testing is they can track for themselves if they are having good cellular function with that strategy. There's been studies that have panned this out. We know that the more ultra-processed food you eat, the higher risk of obviously obesity but also chronic diseases are.

1:24:54But then, of course, there's an amazing study from Kevin Hall just recently where he basically locked people up at the NIH. And for two weeks, he had them eat ultra-processed food. And for two weeks, he had them eat real food. And people ate 7 ,000 more calories in the two-week period when they were eating ultra-processed food versus the unprocessed food. They were locked at the NIH? I've been to NIH quite a bit. 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 the Stanford 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 we have this totally frankenfood, toxic food system that's largely ultra-processed.

1:25:38And it took amazing Kevin Hall to basically do an NIH-funded study where people, what I say by locked, is that they were inpatients at the NIH and had unlimited access to food during each of those two-week interventions. So it was two weeks of ultra-processed food, two weeks of unprocessed or minimally processed food. And they could eat whatever they wanted, as much as they wanted, in both groups. And then they would weigh every single bite that was left on their trays. So they knew exactly, exactly how many calories they ate. And literally just giving people this ultra-processed food, which is devoid of what our bodies need and therefore will drive people to eat more.

1:26:22They 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 a pound is about 3 ,500 calories. And so we have to do these kind of crazy studies just to prove what we kind of know is true, which is that this ultra-processed food environment that's cropped up for the past 50 years is an experiment that has failed. It has failed. Close to 45 % of kids are overweight or obese now. It's not working, and that really is the root cause. So I think a lot of food is about quality and how do we actually really meet the needs of the cells so that our satiety hormones get secreted and we naturally stop eating.

1:27:09Because 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 stimulating satiety hormones, helping the microbiome support that process and then change our reward circuitry, which is done with nutrient-rich, the most nutrient-rich food we can possibly get. And that's why I mentioned the soil because our food is drastically depleted of nutrients. So when we look at that 70 metric tons of food we're eating 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.

1:27:51Well, right now, 60 % to 75 % is ultra processed. So we slash the value because the ultra processing just like slashes the nutrients. We slash the value of that 70 metric tons. And then we have crappy soil because our industrial agriculture system, which means the food in some cases has 70 % less of key micronutrients in it. So that 70 metric tons, what's actually useful for our body becomes so much smaller. So what we want to do is basically expand the value of that substrate we're putting in the body. And that means real food, unprocessed, from good soil, meet the needs of the cells, naturally don't be hungry, maintain a healthy weight.

1:28:33and you know something I talk about is that we could I mean we could talk about nutrition the biochemistry of nutrition all day but in my review of sort of the biology and the biochemistry like there's five main things I think we can strive for in our food that can really help meet the needs of our cells and when it really comes there are obviously more things our body needs but if we strive for these five things we will ultimately I think eat a really healthy diet and that is fiber, omega-3s, adequate healthy protein, a good amount of probiotics, and high antioxidant sources. And if we build our diet around knowing a few things in each of those categories that we really love and stock our kitchen with it and make our meals a mixing and matching of each of those components, and we get a good amount of those, we will give the body a lot of what it needs to have mitochondrial health, reduce chronic inflammation, reduce oxidative stress.

1:29:29It's interesting for me to take a step back from nutrition as it's typically presented and think about the brain, the hypothalamic circuitry that drives hunger and satiety and things like that. And to map that onto what I've heard, and I believe to be true based on my view of the literature, which is that we are largely, meaning these circuits in the brain make us largely amino acid foraging machines because we need those amino acids in order to carry out metabolic processes and reconstruct any tissues that need repair and recovery, not just from exercise, but just daily turnover, removal of waste, et cetera.

1:30:07So we're foraging for amino acids unconsciously. We're foraging for micronutrients. And of course, we need in macronutrients, we need enough energy from proteins, fats, and carbohydrates, or some either combination of the three. I feel like I'm sort of in the dying category of omnivores, right? I'm neither, you know, I'm not meat-based and I'm not a plant-based. I'm 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, you know, where we think of ourselves as getting hungry and wanting to eat.

1:30:45And 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. I love butter. Who doesn't love butter? Of course, none of that stuff in excess, olive oil. But if one looks at kind of that buffet of options, you realize you can get some high quality amino acids. You can get some high quality lipids. You probably want to get more of them from olive oil than from butter, but you can get the micronutrients you need provided those food sources are healthy.

1:31:22Now contrast that with a highly processed diet or even a minimally processed diet. And you can get the taste, you can get the macronutrients, you can get the calories, but you don't, meaning the brain doesn't really have a sense of, it can't directly map taste, calories, micronutrients onto one another. And so you can imagine that the neural circuits, and here I'm, there's 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, right? A Snickers bar, if you like sweets, tastes pretty good, but it's unclear what's in it except sugar, except something, you know, it's got a certain Snickers bar taste, right?

1:32:05But 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. I'm sorry to go long here, but it reminds me of of an idea I had once where like, imagine if you took a pill that greatly increased the level of dopamine, norepinephrine, acetylcholine and serotonin all at once, that's polypharmacology. And it might make you feel a certain way, maybe good, maybe bad. And then afterwards, you'd probably have a bit of a crash from as the drug wore off, no doubt you would.

1:32:43But let's say you wanted more of that feeling. You wouldn't really know what to go look for because you don't know what was in it because it's polypharmacology. So I feel like highly processed food is polypharmacology. Whereas when you are eating foods that create a more pure experience of micronutrients, amino acid content, calories, and taste, those four things map to one another, that intuitively we can start to understand, oh, I like this food and it's good for me and this is enough of it. I don't know anyone of reasonable size that eats like four ribeye steaks. They eat one. I mean, I'm sure there's some freaks out there that do that.

1:33:21But one even small piece of quality meat is very satiating. Yeah. You will self-regulate because the body, like every other animal in the world, is exquisitely designed to regulate hunger on a very intuitive level if we eat natural food. It's, you know, it's I think it's almost ridiculous to talk about calories in isolation because the reason we're eating more calories is because we're eating ultra processed food. And so but I love what you just said, Andrew, about the brain and the polypharmacy. I think that literally is it's I've never heard that said. And I think it's like processed food is like polypharmacy of food.

1:34:04It is the definition of processed food, which I know you talked about with Rob Lustig, the NOVA4 criteria, is literally it's breaking down foods into these constituent parts that were never meant to be separated from each other, like the endosperm of a wheat kernel separate from the bran and the 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.

1:34:41That's the reality. Our insatiable hunger and our chronic disease epidemic fundamentally is a lot of, it's mass cellular confusion. And when you think about what chronic inflammation is, chronic inflammation is biochemical fear on the cellular level. Well, when you put this stuff into the body that's never seen before, obviously that's going to generate some confusion. And you could trace that back to what that really means with leaky gut and all the sorts of the real physiology of that. But there's a wonderful book that is called The End of Cravings by Mark Schatzer. He also wrote The Dorito Effect.

1:35:19But he talks a little bit about what you're talking about, which is the idea that processed food is actually the ultimate sort of food-based variable reward. So in the way that it – like things that – I mean, I'm speaking expert here, but things that the body can't predict what the outcome is going to be are going to kind of get you in that dopamine motivation pathway. And that's actually what processed food is doing is it's – every time we eat a different – we think we're eating a tortilla, but it's like completely different than all the other weird tortillas, ultra processed tortillas on the shelf.

1:35:51So 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 aspartame? 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's pretty much getting a similar thing each time. And so the prediction matching is going to be more conducive to getting off the motivation treadmill for more, which I think is so fascinating.

1:36:37But I think backing up a little bit. 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 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 waiting to bind with these things in our food that will stimulate the cell to make the satiety hormone that, poof, effortlessly makes us not hungry, gets rid of that grip of attachment to cravings that all of us are so plagued by.

1:37:29And I think we have this intense conversation happening in society right now about glp1 analogs and ozempic and munjara 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 society hormones and the processed 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.

1:38:13No, please. Yeah. With the GLP-1 conversation, I feel like so missing from the conversation is the idea that like from a first principles perspective, there's three ways our body could make more GLP-1. We make more cells that make it, L cells of the gut. Each of those cells makes more GLP-1. And importantly, we can also inhibit the inactivator of GLP-1, which is an enzyme called DPP-4. So GLP-1 actually gets rapidly degraded by DPP-4 in the body. So if we can figure out how to inhibit DPP-4, we can raise our GLP-1 levels. What is DPP-4? It's an enzyme that breaks down GLP-1 rapidly. I think you said that and I missed it.

1:38:54I apologize. It's so fascinating. And so how often have you seen in the headlines, Oh, here's some strategies to inhibit your DPP-4. Never, because Ozempic is on track to be the highest grossing med in human history. And just like we talked about in the beginning of the episode, the whole industry, this$4 trillion healthcare 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 GLP-1 from each L cell, and then inhibit the breakdown to the inhibition of DPP-4.

1:39:30For the first one, we know that short-chain fatty acids, which of course are the byproduct of microbial fermentation of fiber in the diet, stimulates the differentiation of more L cells in the gut. So more short-chain fatty acids, more L cells. Can we translate that into support the gut microbiome? Eat more fiber. Eat more fiber. And we had Justin Sonnenberg from Stanford on, a world expert in gut microbiome. And he was a big proponent of, based on work he's done with Chris Gardner and others at Stanford, so happens, of ingesting one to three servings of low sugar fermented foods each day. Things like sauerkraut, kimchi.

1:40:07Again, low sugar variety is probably best. Not kombucha. Yeah. Maybe not. You said not kombucha? Yeah. Because that's going to be like the highest sugar of the fermented foods, which people often go to, but now that's It's costly too. And pretty costly. The sauerkrauts, you can actually make your own sauerkraut. Tim Ferriss had a great recipe for this in The 4-Hour Chef. You have to be careful because you can create some unhealthy ferment. You have to do it the way he describes. So check out the recipe. It's online. Or you can buy sauerkraut. And the brines, drinking the brine off the sauerkraut seems to be good for the gut.

1:40:41That's such a great point, which is that ultimately we want the short-chain fatty acids, which is the medicine that the microbiome are making for us through the microbial fermentation process. And we can basically do that in three ways. One is we can eat more fiber, which is prebiotics. We can also eat more polyphenols because we're now learning that the microbiome actually processes, they ferment polyphenols from our, which is basically you'll find those in colorful fruits and vegetables, spices, teas, cocoa, things like that. So fermentation of polyphenols and fiber to short chain fatty acids, which then we absorb.

1:41:19And then like you just said, in a fermented food, the bacteria in that food will be making short chain fatty acids by fermenting the food in there. And then if we drink that, we're getting the short chain fatty acids directly. So that's the kimchi, sauerkraut, Greek yogurt, kvass, which I'm obsessed with, which is like low sugar kombucha. It's like made with fermenting beets basically. That's good stuff. It's such good stuff. Miso natto. So that's one. That has been shown to differentiate more L cells in the gut. We also know that people with type 2 diabetes have much fewer L cells in the gut.

1:41:53And 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 improve L-cell differentiation. So that's just sort of one set of things. And I don't think the dose on ginseng has been settled, but very high antioxidant component plant. When we look at actually stimulating more GLP-1, you've talked about your remate, I think, having like a mild effect on GLP-1, but there's actually a lot of other things in the literature.

1:42:37Protein, of course, very potently stimulates these nutrient receptor cells. And specifically like valine and glutamine seem to have a potent stimulatory effect on GLP-1. So you're going to find that in like meat and turkey and eggs and things like that. What are your thoughts on supplementing L-glutamine? It's controversial. I know that some people do it in an effort to relieve leaky gut, but there aren't any randomized control trials for that. So depending on one's stance on what's required for kind of a threshold for adopting something, some people will say that's crazy. Other people really swear by supplementing L-glutamine.

1:43:16Maybe it's through this route of increasing L-cells that some of the gut relief might exist. I guess we'd have to explore it. So that's speculative, folks. So this is interesting. These are ways to increase the cells that then make GLP-1. So fiber, prebiotic, probiotic fiber, and fermented foods. Antioxidants, lowering blood sugar, ginseng. So those are kind of the L-cell ones. The actual secretion of more GLP-1, one of the most potent ones, and the study that looks at this, like the bar graphs are very clearly statistically significant, lots of asterisks, is actually thylakoids. Thylakoids. Tell me more about thylakoids.

1:43:55Thylakoids are so fascinating. Thylakoids are actually a structure in plants that are part of the chloroplasts. So chloroplasts, and this also is fascinating because chloroplasts are basically the plant version of mitochondria essentially. And thylakoids are a molecule in the chloroplasts. And there's actually been research that shows that when you eat about 100 grams of spinach, which gives you 5 grams of straight thylakoid over 12 weeks daily, it led to a significant increase in GLP-1. And again, I don't remember the exact. It was two or threefold higher. secretion. So that's a direct simulatory effect of the L cells.

1:44:38And so this equates to 3.5 ounces of spinach a day, which is like nothing. So just getting those green - Raw spinach or cooked spinach? I don't think it actually... It might have said in the methods, but I would imagine raw because you want to get those undenatured thylakoids in the gut. So just kind of another... And actually, thylakoids do a lot of other interesting stuff. They inhibit lipase in the gut and so actually help more fat get down to the distal small bowel and promote satiety. So this is one of the reasons why you talk about, oh, the people who eat all these healthy foods and greens, they're less hungry.

1:45:12It'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 GLP-1 secretion. So other things for GLP-1 secretion, the thylacoids, also fiber has been shown, specific amino acids, so high protein foods, things that involve a lot of valine and glutamine, green tea, and specifically the ECGC that is one of the compounds in green tea, that's been shown to stimulate GLP-1, curcumin. So there's several things that are all in that like whole food, basically things you would associate with a healthy diet, but we actually know they stimulate GLP-1.

1:45:56So those are all things I try to include in my diet. And the last one is inhibition of DPP-4. And that one, there's just actually, when you look at the research, there's some kind of random foods that tend to inhibit DPP-4. Black beans, Mexican oregano, other forms of oregano, rosemary, guava. And I wrote this one down because it's a word I hadn't seen very much before I started digging into this, but muricetin, which is found in berries, cranberries, and peppers, and Swiss chard. So all that is to say, ultimately, many of us are gripped by cravings. And the idea of 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.

1:46:45But a lot of it is literally just communicating to your cells in a clear way through food to help you be satiated. And the science can show us how to do this. And a lot of it comes down to eating essentially what you were talking about, how you eat omnivorous protein, healthy sources with nutrient density and lots of colorful fruits, vegetables, spices, herbs, things like that. So yeah. Yeah, it's interesting. Again, these aren't randomized controlled trials, nor are they peer-reviewed studies. But I have a few friends who I've known for most of my life who really struggled with their weight, carried a lot of excess weight, and were starting to suffer health issues in their – even their 30s, but in their 40s.

1:47:34I'm 48, so they're my peers, and so they're about that age range. And they've all done extremely well, meaning they lost a tremendous amount of body fat are terrifically healthy now by way of basically restricting their food intake to proteins, so fish and meat, eggs, fruits and vegetables. They basically just cut out starches, but I don't think it was the starches per se. I think it was the satiety that comes from eating high-quality protein, fruits and vegetables, and from limiting the number of highly processed foods. And actually the toughest thing for all of them was to stop asking me or themselves rather, like, can I include this condiment, this, this, you know?

1:48:21And what's interesting is all of them now seem to really enjoy eating foods in their more pure form. And I'm not somebody that like pushes this on my friends. They just come to me and say like, how do I lose 50 pounds without having to exercise it all off, you know, as the only source of weight loss? They all exercise as well. But it's just so daunting to try and lose 20, 30, 40 pounds and to do so quickly and then to keep it off because they've all had the experience of going on a diet and then exercising a lot. The point here is that I really think there's something powerful about that relationship between taste, macronutrient value, micronutrient value, and satiety.

1:49:04I 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, and its commercial names are – I forget what the – Ozempic is the commercial name and Munjaro and Wagovi and – yeah. Got it. Is that GLP-1 acts more or less as an appetite suppressant. Right, yeah. Powerful appetite suppressant. Yeah. So many millions of people are now taking GLP-1 analogs. Is that right? I think there were over 20 million prescriptions in the United States last year. Is it expensive? It's$20 ,000 per year.

1:49:43Does insurance cover it typically? Right now, insurance is covering it for indications, but there is an 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 2 diabetes and then the American Academy of Pediatrics recently has talked about giving this to children as young as 12 as part of the first line for overweight and you know I think really it's such a travesty based on the conversation we've had, because what Ozempic does not do in any way, shape, or form is impact the toxic environment that we're living in that's hurting our mitochondria.

1:50:51Losing weight is different than improving mitochondrial function. And mitochondrial function is the root cause of basically every chronic illness and symptom that's torturing American lives today. And so in many ways, it represents like the ultimate band-aid 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.

1:51:33And then there's been conversations, Peter T has waited on this, about loss in lean mass. Part of the weight loss is disproportionately muscle. And so there's a lot of concerns about it above and beyond its ability to lower the number on the scale that we should all be very alert to. Because the reality is that the 40 trillion cells in our body are in an environment in the Western world right now that is not conducive to core biologic functioning. And there is obviously no shot that can mitigate the multi-front assault on our biology that ultimately generates a body that's immensely profitable for those 100 specialties of health care.

1:52:18So, you know, we're living in this matrix and this game of, you know, a devil's bargain between a$4 trillion healthcare and pharmaceutical industry and a$6 trillion processed food industry that all want us to think that, 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, et cetera, 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 learn about metabolic health and improve it.

1:52:53And 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 Ozempic. And then when you trace, you know, unfortunately, incentives there, a huge percentage of these outlets that cover, you know, Ozempic is a miracle drug. Their bills are paid by pharma. 60 percent of mainstream media advertising budget is pharma. And so, you know, I just say that because I think it's a scandal that we give so much airtime to these medications and not to simple metabolic habits that can make us feel, you know, so incredible and really change our core biology.

1:53:32So walking, exercise, eating minimally processed or non-processed foods. You also mentioned temperature. Yeah. Very, very interested in that. But before we go a little bit further down the path of what one can do in terms of having agency over their metabolic health, I just feel obligated to just entertain the possibility. Presumably somebody who's really struggled with their weight a long time, maybe because of excess cravings, challenges in regulating their appetite or whatever. We don't know what the reasons are. Maybe they injured their knee and they can't exercise. I mean, this happens, right?

1:54:09At least not yet. who takes a GLP analog like Ozempic, loses some weight, probably loses some muscle also, one would hope that that would give them the sense of, okay, now I can move my body better. I'll start exercising, eating better as well. I think that I have to imagine that there's a middle case condition where people are not just relying on pharmaceuticals and not just relying on behavioral routes to improve metabolic health, but can do both, right? I mean, And one would hope they are if they're already taking these meds. Or is it the case that when people have a pill or an injection or a potion that gives them the effect that they want, that they just remain sedentary?

1:54:49I think we have to look at history here. I mean, first of all, there have been other weight loss medications throughout history that you've talked about on the podcast, like the fen-fen. And then there was another one, I think, even before that that made people their temperature go up that you've talked about. So the two, these are – I used to work on thermal regulation as an undergrad. So fen-fen was eventually banned because it caused some cardiac issues. I believe it was a stimulant, fen-fluoramine. So sorry, it's not fen-fluoramine alone. It's a combination of things. That's why it's called fen-fen.

1:55:18And then dinitrophenol, which was based on the observation that workers in ammunitions factories were being exposed to this stuff and losing a lot of body fat and weight. It actually made its way into the sports community. It's highly deadly, highly deadly. Just don't even look it up. It's highly deadly. Because the moment people start looking it up, they start thinking about dabbling the way the internet is now. Dinitrophenol. And I think it has to do with sort of processing of mitochondria. I think this is happening in the electron chains in mitochondria. So anyway, free electron. Look it up.

1:56:02Excuse 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 past weight loss drugs. However, if you look at the trends throughout history, the medicalization and pharmacology towards chronic issues has been an abject failure. I don't know of, and I'm sure people can correct in the comments, but of a single chronic condition for which the explosion of the pill to treat and manage that condition has lessened the rates of that condition.

1:56:52The more SSRIs you prescribe, the more depression we have. The more metformin we prescribe, the more type 2 diabetes rates are going up. The more ozempic is being prescribed, obesity is going up. On Wall Street, 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 plummet? No. I can't think of very many chronic conditions for which the explosion of the medication has reduced the frequency of the disease.

1:57:35That'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. 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?

1:58:18No, 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 By the way, as I do this, I can't resist any longer. Casey, Dr. Means brought me this jar of blueberries. People that know me know that I'm a drive-by blueberry eater. So if there's blueberries out on a table, I'm going to take some. I've never eaten during a podcast, but I'm going to now. So I'll try and chew quietly. Do you want some? Sure. Okay. I love blueberries. And no, I don't eat them one by one. But I'm going to try and eat them quietly.

1:58:52So 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.

1:59:26I like it. It feels good. I feel great afterwards for many hours. And I believe there are some health effects and I'm willing to weather the storm of naysayers because more and more data keep emerging. That'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 from 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 platform, but I think about it very, very simply.

2:00:05Throughout 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 the Sierra 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, four walls, you know, insulation, then central heating and cooling, that's like the last 50, 75 years in most homes. And so this idea, our cells have evolved to respond to big swings in temperature that very recently we have totally pulled away.

2:00:49And 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, food energy. That's basically what our environment is, right? And thermal energy is a big one of those. We can speak to our mitochondria with the language of thermal energy and say, hey, it's cold outside. We need you to print more of yourselves or work harder such that we can create heat inside the body to respond to this stimulus.

2:01:31And so that's kind of the framing that I use for it. And this data is hard to know if it's totally accurate, but our population is cooling. I think it was data out of Stanford, actually, that was showing that our temperature has gone down 2 % or something like that in the last 100 years. That fundamentally is mitochondria not working as well as they should. Research has shown we're making less ATP in a lot of our cells, and that's a function of 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.

2:02:08So we're constantly making it and we're constantly recycling it in this like, you know, like basically make it, use it, make it, use it, make it so fast that like we essentially don't change our weight, but it's kind of, and of course, as it's being broken down, ATP to ADP, we release heat. And so I just think of cold as like one of the tools in our tool belt to talk to the mitochondria to say, make more heat. And in a world in which our mitochondria are under siege, I think it's a valuable, often very inexpensive one that we can use. Of course, it does not supplement or replace food, sleep, exercise.

2:02:47But I think it can be a very valuable tool to stimulate through that signal to basically make more heat. And, you know, we know, of course, it can help. And 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 how I use cold. And then on the heat side, you know, just fascinating how that's kind of acting to help metabolic health through the activation of the heat stock proteins, 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.

2:03:24So I put them lesser on my list because we just can't avoid the food and the sleep and the movement, but I think it's a great tool that we can use. I love it. I will just point out that the reason the brown fat is brown at all is because of the density of mitochondria. It's literally brown down the microscope. This is not the kind of fat that is subcutaneous, although it sits around the scapulae, neck, upper back, There's other pockets of it on the body too and such an interesting tissue. Yeah, I don't know why deliberate cold exposure is so controversial. I think it's because people who don't like it and frankly, no one likes getting in it.

2:04:03The best part is getting out and how you feel afterwards. But I think nothing grates on people like deliberate cold exposure if they don't like deliberate cold exposure. And there's no requirement for it, but I think it's a very interesting stimulus. And I think there's also a very interesting relationship between light and temperature because in most areas of the world, as days get longer, meaning more sunlight available, temperatures go up. And nowadays we can really divorce ourselves from all this like day lengthening and shortening temperature fluctuations, which is not to say that we should all be running around in a minimal amount of clothing outdoors.

2:04:37But there's just such beautiful data from Dr. Susanna Soberg's work showing, for instance, that deliberate cold exposure then leads to one feeling more comfortable at cold temperatures because you become essentially more of a furnace, more brown fat. Anyway, we could go on and on, but I think it's yet another lever of autonomy in terms of taking control of one's health. As you said, not as critical as 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 need more words, right?

2:05:18Because the word fasting is so limited. There's so many different parts of this. But skipping breakfast for me would be that or skipping dinner. Sometimes I'll skip dinner. Sometimes I'll skip breakfast. Right. I 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 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.

2:05:59And 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.

2:06:45It'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 just 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 a lot, maybe just consider compressing it into daytime hours, six to eight hour window.

2:07:23Yeah. For me, six is tough. The one meal per day thing is tough. I have friends like Lex Friedman that do the one meal per day thing. I end up eating so much food at that meal that I experience a lot of mechanical distress as typically later in the day. I think an eight to 10 hour window has worked well for me most days. I know as soon as we talk about intermittent fasting, which is what, or time restricted feeding, same thing, which is what we're talking about right now. I'm sure somebody is 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 and particularly the six hour feeding window.

2:08:01I just want to point out. Worst study. As far as I know, I could be wrong, but as far as I know, that study is still in abstract form. It's not yet peer-reviewed. It's like the fact that studies that haven't been peer-reviewed aren't even close to being peer-reviewed are being 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 of day.

2:08:39And it may end up in a journal that is barely worthy of a placemat. 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. And the methods were very poor in that study. It was a recall-based study, I think, for two days of recall of people's diets, which is notoriously very bad in terms of accuracy. So, yeah, and I think I'm not in any way suggesting that a six-hour window is the optimal window. I'm just sharing the data that suggests that compressing the window seems to have a favorable effect.

2:09:19And 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 11 eating events per day and 50 % of Americans eat over a 15-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, 15 hours and 11 events. And every time you're doing that, you're going to be stimulating this glucose rise in the bloodstream, exposing the blood vessels to that glucose. You're going to be turning on all the pathways with insulin to basically store it. And so it's strain for the body.

2:09:57And 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. And that ultimately is metabolic flexibility. The ability for the body, giving the body opportunities to use glucose, but then have times when there's not high glucose and insulin around to actually get into the fat stores. And I think one of the reasons why we have such a massive overweight and obesity rates in the country is because with the way – the culture of eating right now, 11 eating events per day, eating over the course of 15 hours per day, I would imagine the average American body is rarely, if ever, tapping into their fat stores for energy in a meaningful way because we always have glucose available to the body.

2:11:00If you think about, again, the stats about ultra-processed food, about 70 % of the items on the shelves in the grocery store are ultra-processed food, and those ultra-processed foods are built on refined added sugars and refined added grains. So we very rarely give the body the opportunity to rest and move into fat burning. And that's where compressing the eating window can be valuable. Obviously, people have talked about this before, but fasting can be a stressor for the body. especially if your body's not used to using fat for energy. And so it's something to ease into and go slow. But I think if you're slowing down enough to really hear what your body's signal are saying, you can kind of know whether I think your fasting is working for you or not.

2:11:46I can tell if I've got too many other things going on, I haven't slept well, a lot of stress. I can tell that fasting is kind of making me jittery and not feel good. Versus if I 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 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 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.

2:12:20There 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 when we probably shouldn't be eating versus early in the morning, 930. And the glucose and insulin responses for the same meal at 830 p.m. were significantly higher than when eating at 930 a.m. And so, again, bang for your buck, it appears that eating in that earlier part of the day when we're active and our chronobiology is set up for metabolism and activity, we have a lower glucose and insulin response. There's also some evidence that melatonin, which is secreted as we get closer to sleep, has somewhat of an effect on impairing our insulin sensitivity transiently.

2:13:12And 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 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 aim to do three times a week. And post-resistance training, I try and get some starchy carbohydrate in me just to replenish glycogen.

2:13:51And that then tends to reduce my carbohydrate craving later in the day. I love bread and butter, bread and olive oil pastas. And the other day I found this Argentine place, and I love the steaks there, but they had gnocchi. that it took everything I had, 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 walk after the gnocchi. Oh yeah, sure. I'll allow myself to do those things. I'm not super restricted, but again, I tend to eat high quality foods. By the way, these blueberries are amazing. Then you figure out where you got those because they're just tangy enough.

2:14:24I'm doing everything I can to just not take the jar and funnel them 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 did use a levels tracker. And yeah, full disclosure, they're a sponsor of the podcast regularly. And I learned a ton. I'll tell you what I learned. I learned that indeed my blood sugar goes up after I eat, that certain foods, although the foods that did this surprised me, certain foods tend to spike my blood sugar. I'm quite a bit. Grapes, that shouldn't be surprising. Food order was very powerful for me.

2:15:11I know that the data on food order are a little bit mixed and it's controversial, but I like to eat like the French. I like some soup. Then I like my entree. I like the salad at the end. That turned out to have the steadiest and lowest rise in blood glucose for me. And then across time, I also found that I love hot sauna. I go so hot with the sauna that I've been accused by Rogan and other people. I'm going to turn myself into a brisket. 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 possible? Does that make sense?

2:15:47It does make sense, but also the heat can affect the accuracy of the sensor itself. Ah, okay. So that could be it too. But yeah, basically what it allowed me to do is make a few adjustments in terms of foods that I eliminated or 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 anecdata. 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.

2:16:29Always including a little bit of fiber really helped. And that makes sense, right? Slow the absorption of the food presumably. So I found that it was a very valuable experiment for me. Again, this isn't an advertisement. it just so happens I did this and really benefit from it. What are some other things that one can learn from continuous monitoring of blood glucose? What are some things to watch for that might signal a problem? And what are some fun things that one could do to explore and experiment? Because I like to explore and experiment. Yeah. Well, I mean, a lot of the things that you just naturally learned are the things that have been shown in data.

2:17:05And like you said, some of this data, it's like small studies, small groups of people. But for instance, adding fat and fiber to meals has a significant and repeatable impact in populations on lowering glucose response. Fat, probably in some part due to slowing gastric emptying and actually slowing the digestion process. So the rise in the bloodstream 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.

2:17:42And 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 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 just helps you get more from your meal. So what you can learn. So I think step one, the way I think about a glucose monitor, first of all, I'll say the purpose of the glucose monitor is not to game the system and get flat glucose.

2:18:24The 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 diet and lifestyle and where there's a lot of confusion about what's right for us, that can be 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.

2:19:13And so one thing that the glucose monitor does for us is just give us more awareness and agency into 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 or type 2 diabetes because you have the data, which is ultimately I hope the world that we can move towards for a lot of biomarkers.

2:19:58So you can see trends over time, which I think is very valuable. One thing that's fascinating in terms of early prediction of metabolic disease is that you can see how long it takes your glucose to come down after a meal. So in a normal, healthy, insulin-sensitive body, even if the glucose goes way up, it should come way down very quickly because the insulin is binding to insulin receptors and the glucose is getting taken up and it'll lower. What is quickly over the course of - It should be down 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.

2:20:41But 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.

2:21:20My insulin is like 2.5. And if I don't sleep and I am stressed and I have been sitting, my glucose will take way longer to come down. I have become transiently insulin resistant. So I think that's just fascinating to see that. So what that ultimately, the metric that we call that is area under the curve. You want a low area under the curve, AUC, after a glucose spike. So you want a spike and come down quickly. If you shade the area under the curve, it's a small amount. If you go up and then trail off for two to three hours, that's going to be a lot of shading under that curve. And high AUC is associated with insulin resistance, basically.

2:22:00Another thing that you can see is essentially glycemic variability. And glycemic variability, GV, is a metric of how spiky your curves are. Fascinating paper out of Michael Schneider's lab at Stanford in 2018 called Glucotypes Reveal New Patterns of Glucose Dysregulation. Totally landmark study. But basically, they put continuous 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 rolling hills after their meals.

2:22:47You have moderately spiky people. And then you have very spiky people who are going up, down, up, down, up, down, up, down. When you correlate those different patterns of glycemic variability in non-diabetic people, you find that the spikier they are, the worse their biomarkers are metabolically across the board, insulin, triglycerides, et cetera. So basically, they're showing signs through variability of underlying dysfunction that you would never know from a standard test. Those are the people who I imagine are probably going to go on to develop diseases. And yet, based on standard criteria, their doctor is telling them that they're fine, that they're all the same.

2:23:22So 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 actually tracking like a movie of the glucose. So glycemic variability, area under the curve, those are two things. Another really interesting thing you can know from a CGM is dawn effect. So dawn effect is basically a term in the literature for how high your glucose rises right when you wake up in the morning. I don't know if you noticed this when you were wearing a CGM, but some people noticed that the second they wake up, their glucose jumps up 5, 10, 20, 30 points.

2:24:05What's happening here is that the cortisol awakening response to actually get you to wake up and get out of bed, that cortisol can cause you to dump a bunch of glucose from your liver because it's basically saying stress hormone, cortisol, we got to get up. We need glucose to fuel the muscles. Let's dump a little glucose. So it's normal. But what the research shows is that magnitude of Dawn effect is correlated with insulin resistance. So the more the Dawn effect you're getting, I think it can signal maybe the more stress you're under, the more cortisol you have floating around, how big your cortisol awakening response is.

2:24:42But 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 response, that dawn effect is going to be higher. So I don't have the numbers right in front of me, but typically I would want to see a dawn effect, I think, of like less than 10 points. So you wake up and you may very well see a rise. 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.

2:25:19So those are kind of some of the looking at early predictors of metabolic dysfunction. More of the fun stuff is like actually just figuring out like how is food affecting your body? And this is where people really 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 who are trying to make healthy choices. my boyfriend like he when we started dating he started using levels his healthy snack he worked in Venice would be to go to moon juice and get oh gosh I don't want to throw moon juice under the bus here but he would get like tasty stuff 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.

2:26:09And he was actually trying to make a good decision. So now he's 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 grab and go stuff that isn't spiking as glucose. But I think it can help people figure out like, which foods are doing what I want them to do and which maybe aren't. 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.

2:26:43And in many people, it's actually causing a big glucose excursion and crash. And then in some other people, it's not. And so it's really helping with what are the sneaky spikers? And then where's the biochemical individuality? And there was a phenomenal paper out of Israel 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.

2:27:30And 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'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.

2:28:08But it's fascinating to see a lot of women, especially like menopausal women in our community who find that their glucose patterns are getting worse because estrogen is dropping and that's going to 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. And that kind of creates a virtuous cycle. cycle. So those are some of the big things. Those are big. Can I mention one more? I know, I love that. I just, I could obviously talk about this all day.

2:28:46I think it's fascinating, but this is just one more that I think is fascinating because this was a paper in Nature from last year that talked about, and this might actually be one of the most valuable things to people, which is that again, talking about cravings, 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.

2:29:19So a small spike usually won't lead to a crash, but a big spike often will. That's called reactive hypoglycemia, postprandial hypoglycemia. A lot of people think they're dealing with hypoglycemia when in fact what they're really dealing with is that they're spiking their glucose too high and then they're crashing. 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.

2:30:04So 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 manage our cravings is actually to lower the extent of our spikes so that we crash less. And so that was a fascinating 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.

2:30:42Oh, God. But even having too much bright light in a room while one is sleeping at night, even dim light, which is, I don't want to scare people into thinking they have to sleep in complete darkness, although an eye mask can be great, can alter morning blood glucose levels in, I believe it was adults and kids as well. It's 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 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.

2:31:23It's so interesting to think about what's going on in sleep. There's at least one paper that I'm aware of where they had people breathing into a tube during sleep to measure what sorts of metabolism they were undergoing. And it's interesting during a full night's sleep, all of us seem to transition between different forms of metabolism. I'll send you this paper. It's really cool. And I'll put a link to it in the show note caption such that at one portion of the night, we're relying more on, let's just call it sugars for sake of simplicity. Other times we're more ketone dominant. There's a market shifts in metabolism throughout the night.

2:31:56It'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 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. We haven't mentioned that you don't need to even perhaps belong to a gym.

2:32:32And 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 literally 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 in our blood? Because for instance, I would love to know continuous hormone levels, lipid levels, blood sugar levels. I mean, are we moving past just blood glucose and And are there soon to be other things in these monitors so that when we – and by the way, if you haven't used these, it's really cool.

2:33:09You just take your phone, you scan it over the sensor, and then it basically gives you a chart graph of what's going on in your bloodstream. And now they're all – the latest gen of each of them are all Bluetooth now, so no more scanning, which is kind of nice. And 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 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 a comprehensive metabolic standpoint.

2:33:47Different sensors for each, not all in one. So I think we'll have to 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-prescription version of a CGM called the Stelo later this year so there's exciting things happening in the industry and I really do think continuous monitoring it's going to expand to a lot of these other things that you're talking about hormones et cetera. And I mean, it really needs to. I think that, you know, snapshots of a dynamic system are just never going to really be able to give us a full picture on what's going on.

2:34:29And what we really want to be able to do to dig our way out of this healthcare crisis, I think, is empowerment individually and understanding how this rapidly changing environment is affecting our own biology so we can make the targeted choices to hopefully change the environment to be more conducive to cellular health. And continuous monitoring is a closed loop biofeedback 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 a lot's coming down the pipeline. Love it.

2:35:04Yeah. Let's talk a little bit about mindset. This is a really interesting topic that you include in your book. We've had guests come on and talk about growth mindset. Stress can be enhancing mindset. I'm big on mindset because I'm interested in how our cognitive reframing or cognitive framing can just change the way our biology works and vice versa, of course. But you talk about mindset in a certain context. And one of the favorite passages around that that I really enjoyed was the relationship between kind of like trying to control everything and nature, you know, and how getting into nature itself can be valuable for us.

2:35:44So maybe touch a little bit on mindset, if you will. And what are your thoughts on nature, literally getting out of doors? Yeah. So 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.

2:36:22And 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 diabetogenic effect. It literally causes our blood sugar to go up when we feel stress. And that can be a fascinating unlock for people to realize, I kind of feel like I'm okay right now, but my body is telling me something different. It's telling me that biochemically, I'm actually releasing energy stores from my liver, glucose, to fight some threat that I wasn't really aware of. So we definitely understand there's this link here, but it's certainly not made its way into clinical practice.

2:37:04So the way I think about it is that what we know about the cells, and especially the mitochondria, is that the mitochondria are more than the powerhouses of the cell. They actually are a part of the cell that is constantly tracking 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.

2:37:38It 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 hear 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, and I think what's really maybe the most unnatural thing about our modern world, you know, the food, of course, is unnatural.

2:38:2870 % 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 8 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?

2:39:17And 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, unresolved 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 in us sort of all the time. What's coming in through our devices, our phones, our computers, the media that we're exposed to that's constantly giving a fear signal.

2:39:52And I think on a broader level, a big Western one that we don't talk about is literally like existential fear of mortality. We have a very de-spiritualized, very uniquely death-fearing culture. 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 Western system, to the extent that our entire healthcare system. Actually, I think, you know, we've built it around like, we're not going to, we're not going to help you thrive. We're just going to do whatever we can to make sure you don't die.

2:40:34Like 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 healthcare 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.

2:41:31What 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 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 % 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, I don't know where to channel my energy. It's just, it's short-circuiting, I think. So many things happen when we go outside, as you know.

2:42:18I mean, even what the vision system is doing to our anxiety levels, we are getting sunlight, which, of course, for, you know, complex reasons is very helpful for our metabolic health. Separately entrains our, you know, chronobiology and, you know, light from the sun is 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.

2:42:59We 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, quarter moon, full moon, all these things, it's actually – it entrenches 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 when we are locked inside of the four walls of our house, I think we get very scared. We get very controllable.

2:43:46And the system wants it that way because when we are scared and when we are existentially 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, 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, try and get that 93.7 % down to like 50%, spend as much time as you can outside.

2:44:32We 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 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 all the trees around us when we take that walk, even in a city, We see all the trees, all those plants, all those leaves are making the oxygen that literally let us do oxalate phosphorylation.

2:45:30And 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 in 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 I think a lot of people will find that their health gets a lot better if they spend radically more time outdoors.

2:46:22And I think a lot of people might say, well, I can't. I work on a computer. And I'm like, Rome is burning. We're sick as hell right now. We need to get creative. Move your computer outside. Take a walking meeting. Open your mail outdoors. Chop your vegetables on your balcony at your apartment. Like we have to find a way to connect back with our source, understand that the world is abundant and harmonious, re-entrench 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 a really, I think, joyful experience of our health journey that's rooted fundamentally in connection rather than us being siloed from all of this, which going back to the beginning of the conversation, that's fundamentally what's wrong with the healthcare system.

2:47:17It's silos. And we have siloed 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's many other things we can do to change our relationship with fear. But 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.

2:47:55And I love it for many reasons. I think 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, back to nature, the only truth. And I asked him what he meant by that and because Rick can be a little bit – I'm cryptic sometimes. Not always, but sometimes. And what he was saying is it's a real thing. You can immediately feel the connectedness between the human experience and life of other types, plants, animals, sunlight, the circadian rhythms and the rhythms of light and dark because they impact us so powerfully. I mean, if there were ever a force in the world that impacts how we feel, it's the circadian rhythm.

2:48:46It's the rising and setting of the sun. It's the impact of light and dark. And then all the other things that you talked about today, 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. It attempts to do a lot of good things too, I believe. I'm a believer in technology. But that it, if I were to translate, it sounded like 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 there are a number of, let's just call them programs in the world that then sell back the illusion of some sense of agency little by little, right?

2:49:26A temporary agency, and then puts you back into the cycle. And there's something about going into nature, which just 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 brain, reducing anxiety. We know being outdoors for two hours or more per day reduces myopia, nearsightedness. This is independent of all the other effects of circadian rhythms, et cetera. Anyway, and on and on. So I second and third and hear all the statements you made before.

2:50:03I 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, cold exposure, sleep, high-intensity interval training, and make a case for each and all of those as it relates to the underlying biochemistry. And weave all that together in a way that then 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 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.

2:50:47It's that it is quietly but powerfully oppressive 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 basic and fairly easy to access things, making better choices about food, timing, quality, amount, exercise and on and on. So I'm running long in my response to your much more eloquent description of mindset. 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.

2:51:27I'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 is in some ways a heretical idea, 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 front to back. I haven't tried the recipes yet, but thank you for bringing the blueberries. I'll try the recipes, at least one of them. And I just wanna thank you for sharing what you do.

2:52:03and for continuing to do what you do. We need it and we appreciate it. So thank you. Thank you. Thank you for joining me for today's discussion about metabolic function with Dr. Casey Means. If you're learning from and or enjoying this podcast, please subscribe to our YouTube channel. That's a terrific zero cost way to support us. In addition, please subscribe to the podcast on both Spotify and Apple. And on both Spotify and Apple, you can leave us up to a five-star review. Please check out the sponsors mentioned at the beginning and throughout today's episode. That's the best way to support this podcast.

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2:53:39Thank you for joining me for today's discussion about metabolic health with Dr. Casey Means. And last, but certainly not least, thank you for your interest in science.