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

40:48And 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. And I love the visual, and I hope people will really hold it in mind, so I'll reiterate it. The translocation of these energy utilization stores, vesicles, as you call them, these little packets from the center of the cell, out to the cell surface, where then they can be involved, involves, excuse me, in metabolic processes and the utilization of energy in ways that otherwise, they wouldn't, and glucose disposal being a big part of this.

41:41So I have heard that a short walk after a meal will reduce blood glucose in a way that's really dramatic. Huge amount, 30, 35 % just taking a walk around the block after a meal. That's definitely a prescription. I think everyone should do, because the research is so strong on it, is that building in simply a 10 minute walk around the block, or a dance party in the kitchen, moving your muscles for 10 minutes after a meal can drastically reduce your glucose response, because you're just bringing all those channels to the membrane, you're taking up the glucose you're using, and it's a whole different physiology than sitting on the couch after a meal.

42:16That'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'm forced to walk more, I always just feel so much better. We also know that the optic flow that one experiences with walking has some interesting effects on the limbic pathways and quieting of some of the anxiety and stress related pathways. This links up with things like EMDR, although there are factors that are separate from EMDR. Basically moving through space, not outer space, but walking through space with optic flow, has a certain anxiety reduction function in the brain, which are beautiful data there, in my opinion.

42:59Okay, 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, getting breathing hard for some minutes each week, maybe a couple of 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. We've got walking, we've got resistance training, we've got high intensity interval training, we've got endurance training, and then we've got sort of more like zone two. So we've got these different flavors of how we get our heart rate up, how we get the blood flowing, what we signal to the cells.

43:46And each one actually has a slightly different impact on the mitochondria. When we think about biogenesis, we're thinking mostly endurance exercise, and really more of that zone two. And that is really gonna be a stimulus inside the cell to print more mitochondria. When we think about improving mitochondrial fusion, high intensity interval training is really, really good for that. When we think about resistance training, it's like that's muscle hypertrophy, we're gonna 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 actually make a lot of sense.

44:27It'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 strain of certain activity. So 75 minutes of strenuous activity or 150 minutes per week of moderate activity. So that actually makes a lot of sense. 80 % of Americans are not meeting those very basic guidelines, and 20 % of Americans don't get any physical activity really at all. The 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.

45:04But I think those are pretty reasonable resistance training, two to three times a week, most major muscle groups, and working to get the heart rate up, moderate level for 150 minutes a week or strenuous for 75 minutes a week. Those are going together to be potent stimuli for biogenesis, mitophagy, mitochondrial fusion, for increasing antioxidant enzymes that are gonna protect the mitochondria from that oxidive stress. And the one that's just actually not in there in the sort of the basic recommendations for Americans is the walking. And I would just absolutely add to that at least 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.

45:55It's just a few minutes a day. So that right there are gonna be like a big, multifaceted set of signals for increasing mitochondrial capacity in different ways. Terrific. What are your thoughts on under the desk treadmilling? I don't own one of these, and I try and get walks, and I definitely do my three resistance training sessions per week, different muscle groups on different days. So it ends up being each muscle group as it directly wants and indirectly a second time. But I like to do a long hike once on the weekend, run in the middle of the week, that's 30, maybe 35 minutes, and then some VO2 max really short work out 12 minutes total where basically I'm just going for the feeling that my heart is gonna jump out of my chest, and I'm gonna die from gastrovera, but luckily thus far I haven't died nonetheless.

46:45The total time commitment isn't that great, but I find that I'm at a desk a lot, and I have a standing desk. Is it wise to get a treadmill to treadmill under the desk? Seems like it would be one of the best things one could do. I'm a massive fan of under treadmill desk, because genuinely I believe that if we move more of our daily activities that were 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 desk 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 work day, so not a lot at very so speeds for two weeks.

47:37And 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, assuming it's linear progressions, which is not the case folks. But that's what I'm saying. It was a pretty, but that was there in the discussion. And, 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 under desk 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 forgot and I'm even on it. Is that right? So you're able to work without thinking about having to, to, to treadmill. I am putting it at such a slow speed. I think I'm usually walking at like one mile per hour. I mean, it's very, very glacially slow. I do put my ororing on my second toe when I do this because otherwise, it doesn't count my steps because if your hands are at your desk, they, they, it won't count your steps.

49:03Because the ororing's measuring hand is gone. It accelerometer, 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 gonna get six, seven, eight thousand steps and then throw in a couple other short walks throughout the day and you're, you're getting there easily. So it's just a, it's just a great way to build back in what modernity took away. And that unfortunately is unavoidable, that, that regular movement for good physiology. So I'm a big fan of them and the data suggests that for a couple hours a day, they can actually have a, have an impact on body composition, which I think is, is a great, easy, inexpensive thing for people to do.

49:45But if you, if you don't want to buy one, like just set those timers and, and build in the walks, you know, throughout the day outside. Terrific. You know, I'm a, I'm a fan of getting walks when I can. I also, I wonder your thoughts on, there was a study, not sure if you're familiar with it, published out of the University of Houston, where they looked at what they called it, soleus pushups, which all the gym goers are gonna roll their eyes. Imagine sitting down and raise, pressing your toe against the ground and raising your heel. So kind of like seated calf raise, but no way, right under the desk.

50:20This 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, it caused rather a disproportionate use of blood glucose. So it mobilized blood glucose in a good way. And the idea was if people would, it's not just bouncing your knee, but would actively push their toes against the ground and raise their heels as they were seated in 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.

51:00And it was interesting to see that sort of a tax that I got. Like people really didn't like the idea that this was any different than so -called neat non -exercising activated thermogenesis. So it's known that people that fidget a lot or move around a lot burn a lot of calories. This actually goes back to some really beautiful work. Several decades or more ago from Rothwell and Stock who talked about like the fact that animals and people who fidget a lot burn a lot of energy. They tend to be thinner, they tend to have lower adipose tissue stores. And it's because they're just burning a lot more calories.

51:33And this is actually what people who suffer from anorexia, which is by the way the most deadly of the psychiatric condition. So it's probably about true anorexia are encouraged not to do because they either do it spontaneously or they learn that it's a very efficient way to burn calories. And that's not what they need. But many people do need to burn more calories. So bouncing the knee, that thing that drives everybody crazy, if you're not the one doing it, soliist pushups, 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.

52:03It's all coming back to just moving the body as much as possible during the day. Contracting muscles, contracting muscles. It's medicine. And I find the concept of neat just endlessly fascinating. Because we kind of come up with this term non -exercise activity thermogenesis. And the data is really good about it. It's basically shows that this is a prime potential intervention for the obesity epidemic. And it all goes back to the cell. It's essentially a stimulus that's telling the body to stay metabolically active as opposed to keeping all those metabolic pathways dormant during the day. And I think that it is funny though, that we have these acronyms for basically, like this is just the way life was 100 years ago.

52:51If you look at the 1800s, almost 100 % of Americans lived on a farm, basically 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 movement was just built into everything we did. And you think from there, what has happened? 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 outdoor open -air markets, then it's supermarkets.

53:30Then it's now it's literally buying food online with the click of the button. And now some people aren't even doing that. They're literally on the food delivered to them with Uber Eats. So at every level, we've taken away movement from everyday life. And now we have sort of an acronym to like, bring it back in. But really it's about just, you know, giving the body stimulus stimuli that the cells have been entrained to expect throughout all of human history and building the back end to 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.

54:12And even for people who are listening don't have a chronic disease. Any real chronic symptoms we're dealing with, and just the fact that we're not feeling as good as we could. Like the way out is pretty simple. Like it's some of these basic things, like walking more throughout the day, moving more throughout the day, getting outside, you know, eating clean, unpoisoned food. The, 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.

54:57And like some of these things, like the neat, like the walking, like, it's emblematic of the fact that some of the simplest solutions are the ones that are by far the most effective. And I think, I think the biggest misconception in healthcare right now is that the way out and the way to get really back to true, incredible health is complicated. Like it's really not that complicated. We've got to move more, you know, throughout the day, that's one of them. And, you know, on each pillar that we touched on earlier, food, sleep, all of this, you know, when we talk about the simple habits that we know work, the reason they work is because they all positively impact that mitochondria, they positively impact oxyofstress, they positively impact inflammation.

55:39So yeah. I love it. I love simple solutions that hit multiple cellular pathways that can make everybody healthier. I'd like to talk about assessment, blood tests in particular. I remember in college, I was just very curious about blood testing and I had read a little bit about it. 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 wanted to do that and they're like, no, 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.

56:18And nowadays, thanks to your efforts, your innovative and engineering efforts and the efforts of others. There are ways to measure what's in your blood and 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 Tia. Fasting blood glucose, continuous blood glucose, post -meal, et cetera, just kind of evaluating how exercise food, et cetera, impacts blood glucose and then all of the other categories open because my point here is not to answer the question.

57:08That's what comes to mind. You know, 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 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?

57:45But which you still might have to fight your doctor for. So the first few that you will not have to fight your doctor for and are often free on an annual physical and literally define metabolic syndrome are fasting glucose, fasting triglycerides, HDL cholesterol, hemoglobin A1C, total cholesterol, waist circumference, and blood pressure. Okay, sorry, I hate to interrupt. And my audience hates it even more. But I'm going to just could you just explain what each of those is and what it corresponds to? Yes. Great thing. And I will say first of all, the reason I'm choosing these, it's not even my own choice really.

58:19It'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 metabolitized functional use those biomarkers. So I think because of that, it's important to know them. And the two studies that I'm referring to are one from UNC in 2018, which showed that based on those biomarkers, 88 % of American adults have suboptimal metabolism. And then the follow -up study from the Journal of the American College of Cardiology from last year showed that that number has gone to 93 .2 % of American adults are suboptimal in their metabolism.

58:55And these are the metrics that they use, and they're very basic. If you had to pay out a pocket, they would be less than $100. So let's talk through them. Why they're great is because together, they give you kind of like a tapestry of what's actually happening inside the cell. If you choose to look at them that way, if you read the tea leaves of them, are the doctors often, if they see all these lab tests, it'll be an electronic health record. We've all been through this experience. 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.

59:33And the doctor will basically, it's very algorithmic. Oh, you know, your LDL's high, we need to bring it down. Oh, your glucose is high, we need to bring it down. Oh, your blood pressure 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. So let's start with fasting glucose. So fasting glucose, when you look at these studies that I'm referring to, they call optimal less than 100. So to define whether you were in that 88 or 93%, you had to essentially be in the, their optimal range for all biomarkers, not on medication.

1:00:08So I'll quickly run through what their ranges were. My ranges for optimal are tighter than these. But fasting glucose less than 100, triglycerides less than 150, HDL above 40 for men, or 50 for women, hemoglobin at 1C less than 5 .7%. Total cholesterol to HDL ratio, less than 3 .5 to 1, waist circumference less than 35 inches for women, or 40 inches for men, and blood pressure less than 120 over 80. If those things were in those ranges and you weren't on medication for blood sugar or blood pressure or whatnot, you were considered optimally metabolic healthy. That's now 6 .8 % of Americans. All of these biomarkers are easy to change in one to two months, I would say, with simple lifestyle habits.

1:00:58Could 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. Yeah, totally. But I'm not sure that I adhere to that. I'm not sure I don't adhere to that. I'm not sure about a lot of things. But I am sure that most people think of them that way. So just as to stay functional here, we'll frame it that way for now with the caveat that that might not be the whole story. Right. Isn't the whole story. But triglycerides fat in the blood, fatty stuff.

1:01:34But so key to understand about the triglycerides, it's not, we don't want to confuse triglycerides with eating more fat. Traglycerides are a storage form of excess carbohydrates in the blood. So this is why it can tell us something about it. And I know you and Rob Lustig talked about this at length, but it's... And Lane Norton. And 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. Right. But then they also think the macronutrient fat. Yes. We just need more words to better parse the reality.

1:02:09In biology, we call the two major groups of people, lumpers and splitters. Yes. Lumpers like to lump everything together. It oversimplifies and complicates splitters. Like to split everything, give a name for everything, individual name for everything. It complicates. And so there's a middle ground, right? There's a land of reasonable people and nomenclature. And unfortunately, that does not exist on the internet. Nor does it exist in any one specific subfield of medicine or science. I mean, so much of the confusion out in the world is because of a lack of adequate language. In order to explain.

1:02:41Okay, so the triglycerides are a reflection of excess carbohydrate intake. And how it's helping us with that tapestry of understanding the trifecta of bad energy is that if you think about it, let's just go back to that cell and that poor mitochondria that's being absolutely decimated by our environment and its capacity is low. Okay, so that might get mitochondria's like, I can't process glucose or fatty acids to ATP very well. So I'm going to block their entry into the cell. So now you've got glucose rising in the bloodstream. So, okay, fasting glucose, that was one of our biomarkers. If that's going up, that is a little bit of that tapestry of maybe something's going on inside the cell that's blocking the entry into the cell.

1:03:20So it's rising the bloodstream. Okay, well, where's all that? The body does not want lots of glucose floating around in the bloodstream because it can literally independently cause endothelial dysfunction, which is basically blood vessel problems. It can cause oxidative stress in the bloodstream. It can cause glycation, which is sugar literally just sticking to things. The body doesn't want that glucose high in the bloodstream, so it converts it to triglycerides to be stored in a storage form of energy. That's a key point that I think is helpful to understand is that the body, it's always trying to kind of keep things in the right range, so it'll convert things.

1:03:56So 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 in process. It's a sign of mitochondrial dysfunction and chronic overnutrition too much substrate, not enough processing. Glucose is going to go up, triglycerides are going to go up. And so then if you kind of squint and read the tea leaves, it's like, huh, I think metabolic dysfunction. And what's fascinating is that the travesty in our healthcare system is that a patient might go into the doctor and they're fasting glucose is 99, 1 point under what we'd consider the normal range and their triglycerides are 149, 1 point under what we'd consider the normal range from these things.

1:04:47That doctor might say to that patient, you're totally fine. Both glucose and triglycerides are normal. But that's just really problematic because they're on the upper end of normal for both of those. And so really what that would say to me is someone thinking about the mitochondria is like, this person is definitely metabolically dysfunctional. They're on the highest end of normal for both triglycerides and glucose. There's something, there's definitely insulin resistance going on here. I would much rather see that glucose at 73 and that triglyceride at 50, which to me would say, oh, this cells processing through energy, great.

1:05:24And things are moving through and we're not backing up in the bloodstream. We're not converting to triglycerides. So that's where really optimal ranges get in. But 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.

1:06:02And you can imagine that if the concentration of glucose is higher over time, more glucose is going to stick to red blood cells. And that's going to create a higher percentage of glycated hemoglobin. So that's why that lab is represented as a percentage. So less than 5 .7 is what we want. You want those cells nice and smooth and slippery. No, no sugar stuck to them causing dysfunction. And because blood cells last for about 9 to 120 days, hemoglobin A1C is giving us a basically a snapshot of average blood sugar levels over 9 to 120 days. And if that average is higher, again, probably a sign that cells are rejecting glucose from the cell and it's causing a rise in the bloodstream.

1:06:45And 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? And a really, the fascinating link is that when that cell becomes insulin resistance, which again is a compensatory mechanism for mitochondrial dysfunction, the insulin is going to rise in the blood because the body's insulin resistance. So the body's going to turn out more insulin to try and overcome the insulin block to drive the sugar into the cells. So insulin levels rise.

1:07:20Well, insulin is one of the key activators of nitric oxide, which is the molecule in the blood that dilates and relaxes blood vessels. And so when we become insulin resistant and we're not responding to that insulin signal, we end up getting less nitric oxide activity. So this is how kind of looking at even these very basic, very cheap biomarkers through the lens of basic cellular physiology, we can start to see, man, my body might be like underpowered. I might 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.

1:07:57It's sort of comes across to many people as old school, right? But when a TIO 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. Vessels and capillaries are constricted. Cells aren't able to use the energy that's coming in. There's excess energy. There's build up of metabolic waste. There's all this stuff. And now we can start to see the picture. Yeah. And it's trying to emerge. And as you mentioned, briefly, these markers can be put into healthy range or maybe even fantastic range in a very short period of time.

1:08:40So we'll talk about how to go about that. In terms of getting a basic blood test is your physician, what's the secret code? I'll give away one that a former guest who's also an MD shared, which is oftentimes if you ask your physician for a blood test, they will say, well, unless there's a particular need or you're struggling with something they won't give it to you. But if you have a shift from baseline in a symptom or in a number, that can help. All the physicians are going to come after me now with, I guess, with deathoscopes. I'm willing to stand my ground. If you want a blood test, it's often useful to mention that there's been some market shift.

1:09:23You want to be honest, right? But some market shift in sleep, in lifestyle, in how you feel standing up, sitting down. I'm not trying to lace people's minds with ideas to create narratives here. But oftentimes where physicians are resistant, they'll be more amenable if they understand that, hey, something's changing. And the patient's saying something's changing. It actually would be irresponsible of them to not give the blood test. So there you go. Bring it on, MDs. Yeah, truly. And I think the nice thing about these, again, very basic tests. And there are so many other tests that I talked 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 function, oxidative stress, chronic inflammation.

1:10:10But the ones I'm mentioning are the ones that you will not have to fight with your doctor about. Oh, good. Everything I just mentioned, like the doctor should order on an annual physical. And it's really about us learning to actually like read the tea leaves of what they're saying and not look at them in this algorithmic way. But like how together, if they're creeping up, or if many of them are a little bit high, like we need to focus 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.

1:10:43Now in the book, I give scripts to literally talk to your doctor with. Oh, just. Because you are going to get pushed back. Often, if you ask her a fasting insulin, I would say probably, I mean, maybe 85 % of people are going to have their doctors say they won't order that for them. So I actually think there's a huge benefit. I hate to say it, but like going outside the system, this is where I think innovation has been valuable. There's a lot of like amazing companies doing direct to consumer lab testing, so you can basically avoid the hassle. And some of them are very affordable. There's 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.

1:11:27So you don't ever have to. And then they do interpretations inside tracker, next health levels is doing labs. And so there's a lot of this springing up because I think people are sick of fighting with their doctors to get a crumb of information about their health. And it's, it's, we should probably be testing these. I would say three to four times a year. And the beauty is is that like, I think a lot of what keeps people down in the health world is that they're confused about what to do. There's a lot of noise, there's a lot of different strategies. You know, do I do, you know, paleo keto, carnivore vegan, Mediterranean.

1:12:10Do I do hit or zone two or eccentric? It's like there's so much noise. And the beauty with having a plan for understanding your biomarkers regularly is that you can cut through all the noise, try a strategy, see where you stand, retest in a few months and see if you're moving in the right direction. 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 like, if your labs are optimal, and the range they just mentioned are not optimal, like you want to actually get to better than all of those if you want to be optimal.

1:12:48If you're key metabolic biomarkers are optimal, if you feel absolutely freaking incredible and you have no symptoms, then you're probably doing the right strategy, whatever that is, vegan keto, whatever, like an exercise in your lifestyle because that is showing that your cells are fundamentally working properly. So I think that's just a really empowering message. And now there's phenomenal companies that are cropping up to basically help allow people to do this on their own schedule, which I think is really the future of health and actually will help lessen, I think some of the intensity of the diet wars, you know, because it's like people can just say, like, I trust my strategy.

1:13:26I 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 pre -diet, exercise, post -diet, exercise photos on social media are now starting to also include numbers, which is kind of interesting. I mean, obviously these aren't randomized controlled trials, but it's cool to see people posting their numbers of things that are not just related to aesthetics, but our 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.

1:14:07Thanks 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's a little high, maybe a few other things are okay. So I'm kind of in them, you know, not in the red zone, but I'm in the like, 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 in movement before. What are a few others, and maybe we could start to touch into nutrition a little bit, and then we'll pivot to insulin and blood glucose.

1:14:47I think on the highest level, it's about running through what are the science -based things that we know in our environment can lead to metabolic dysfunction, and take honest stock of how those factors are playing out in your life, and then choose a few to start moving in a different direction. So the ones that I think are ones that we can really control, and that we know based on the science or impact in 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.

1:15:37So 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 that those are the things, those are the things in our environment that we need to basically improve to give ourselves the best capacity, and then of course checking your biomarkers to make sure your interventions are working. But food, I think, is one that is 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.

1:16:12For a lot of reasons, our bodies are basically 100 % molecularly made from food. It's so wild. It's so wild. Every time I think about that, it kind of blows my mind. 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 we have this conception in our Western world that the body is a thing that we're with throughout our life, because we kind of look the same and we age slowly. So it's like Casey is a thing and Andrew is a thing, but the body is actually a process. The body, and there's this amazing Taoist statement.

1:16:48Life is a process, not an entity. I love that. And the way... 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. Whereas 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.

1:17:33I think so much in our language, actually, of healthcare, both our Western sort of desperaturalized nature, like we don't really have a lot of curiosity with process, but even the ideas, the way we talk about disease, I have diabetes. And we don't even talk about diabetes cures, which now a lot of people are curing their diabetes. We call it remission. It's this thing that's a part of you. And I think I just love this idea of we're evolving every day, and food is so important, because again, we take in 70 metric tons of food in the lifetime, 2 to 3 pounds per day, one metric ton per year on average, and that is like the printer ink.

1:18:11That's the 3D printer ink to create tomorrow's version of ourself, which is molecularly different than the Casey of today. That's a hopeful message, because if we can give the body food, which 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 ourselves 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 calories, 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 drill, 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 under explored topic.

1:19:42So 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 11am, noon or one. I'm okay, not eating until then, and just, you know, water, electrolytes, and caffeine. It does mean just fine. I can exercise, et cetera.

1:20:24But once I start eating, I really enjoy eating, and I mostly like the proteins. I like meat and fish and eggs, and I like cheese and vegetables, and carbohydrates, and fruit and all of it. I like all the stuff, and I tend to like single or few ingredient foods. I just naturally do. So I've been lucky in that way. But I know a lot of people like sandwiches, processed foods, things that are combinations of ingredients. What do we know about kind of, I don't want to say optimal, but if one we're going to explore different ways of eating for sake of adjusting these biomarkers in the right direction and improving metabolic health, is there kind of a generic jumping off point?

1:21:06Would most people, for instance, be wise to cut back on the total number of sugars, or the total amount of sugar, rather, perhaps reduce the amount of carbohydrate and replace it with some lean quality protein? I mean, are there generalizations that we can make, or is it really all just about not getting excessive calories and trying to get those calories from the most nutrient rich sources? Just drilling it on two things you just said there. One thing you said that was interesting was that you're lucky that you like all of those foods. The second thing was that just about not getting excess calories.

1:21:39But I think what's interesting about both of those is that I would argue that the reason you like those foods is because you have given your body enough whole real foods that now everything in your biology, neurobiologically, your reward circuitry, your microbiome, your satiety, hormone, threshold, all of these are now basically creating a situation in which you like those foods. And then the caloric thing fits into that because the reason we're eating excess calories, the reason chronic nutrition is happening, and the reason we are quite literally in the United States eating ourselves to death for the first time in human history is because we're not eating real food.

1:22:23And we're eating 60 to 75 % of our calories of ultra -processed nutrient depleted foods that fundamentally don't give ourselves what they need. And a real premise that I think is so important to realize is that our cells are brilliant. And if the cells aren't getting what they actually need to function properly, they will drive you to eat until they get their needs met. Unfortunately, because the ultra -processed food is designed to be highly addictive, and it's devoid of what the cells actually need for good function, we end up eating ourselves into a grave. And now almost 80 % of Americans are overweight or obese, close to 50 % of the country is obese.

1:23:14We literally gloss over this as a culture. It has become so normal in such a short amount of time, but I always think about the fact that like there are really no other animal species in the world that have obesity and chronic disease epidemics. And they don't have social media, they don't have experts, they don't have PubMed, they don't have the FDA, they don't have the USDA, they don't have any of it, and they have somehow figured out a way to stay at a healthy weight and to not get heart disease. And it's because they're eating real food that meets the needs of their cells. And so I think to just boil that down, the root cause of the promise that we have a toxic food supply that's no longer filled with the molecular information that our body needs to know to be satiated and to function properly.

1:24:01And so through the complex biology of satiety hormones and neurobiology and microbiome function, we are driven to eat so, so, so much more. So truly, the jumping off point for anyone on the quest to better health is to eat as much real unprocessed food from good soil as possible. And I've 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 bodies actual, fundamental needs. And the good thing about biomarker testing is they can track for themselves if they are having good cellular function with that strategy.

1:24:47There's been studies that have panned this out. We know that the moral to process food you eat, the higher risk of obviously obesity, but also chronic diseases are. But then of course, there's an amazing study from Kevin Hall. Just recently, where he basically locked people up at the NIH, and he for two weeks he had them eat ultra -processed food and for two weeks he had them eat real food, and people ate 7 ,000 more calories in the two -week period when they were eating ultra -processed food versus the unprocessed food. They were locked at the NIH. I've been to NIH quite a bit. I don't, it's great for a day job or a day visit.

1:25:22I don't know that I want to be locked there. That sounds like a, 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 franken food, toxic food system that's largely ultra -processed. And it took amazing Kevin Hall to basically do an NIH -funded study where people, what I say by locked is that they were in patients at the NIH. And every had ad -lib unlimited access to food during each of those two week interventions. So it was two weeks of ultra -processed food, two weeks of unprocessed or mentally processed food.

1:26:00And 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. 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 we'll drive people to eat more. They ate 500 calories more per day for a total of 7 ,000 calories more in that two weeks. And they gained about two pounds and then lost two pounds in the unprocessed group, which makes sense, of course, because a pound is about 3500 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.

1:26:49It has failed. You know, close to 45 % of kids are overweight or obese now. Like it's not working. And that really is the root cause. So I think a lot of food is about quality. And how do we actually really meet the needs of the cells that our satiety hormones get secreted? And we naturally stop eating because just telling people eat less calories, but eat whatever you want. That just doesn't work. We have to inspire the body to not want to eat excess calories, which we do by stimulating satiety hormones, you know, helping the microbiome support that process and then change our reward circuitry, which is done with nutrient rich.

1:27:34The most nutrient rich food we can possibly get. And that's why I mentioned the soil because our food is drastically depleted of nutrients. So when we look at that 70 -metre tons of food reading in the lifetime, it's just fascinating. That's that's the information for our body, what it's going to be built from, how it's going to function. Well, right now 60 to 75 % is ultra -process. So we slash the value because the ultra -processing just like slashes the nutrients, we slash the value of that 70 -metre tons. And then we have crappy soil because our industrial agriculture system, which means that the food in some cases has 70 % less of key micro nutrients in it.

1:28:12So that 70 -metre tons, what's actually useful for our body becomes so much smaller. So what we want to do is basically expand the value of that substrate we're putting in the body. And that means real food unprocessed from good soil, meat in the needs of the cells, naturally don't be hungry, maintain a healthy weight. And you know, something I talk about is that we could, I mean, we could talk about nutrition, the biochemistry of nutrition all day. But in my review of sort of the biology and the biochemistry, like there's five main things I think we can strive for in our food that can really help meet the needs of our cells.

1:28:50And 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 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 on to what I've heard, and I believe to be true based on my view of the literature, which is that we are largely, meaning these circuits in the brain, make us largely amino acid foraging machines, because we need those amino acids in order to carry out metabolic processes and reconstruct any tissues that need repair and recovery. I'm not just from exercise, but just daily turnover, removal of waste, etc.

1:30:07So we're foraging for amino acids unconsciously. We're foraging for micronutrients. And of course, we need macronutrients, we need enough energy from proteins, fats, and carbohydrates, or some either combination of the three, I feel like I'm sort of in the dying category of omnivores. I'm not meat -based and I'm not plant -based. I'm in omnivores. I think most people are omnivores, actually. But omnivores aren't discussed quite as much as the other categories, at least not on social media. But that we think of ourselves as getting hungry and wanting to eat. And I think eating the food, some of them that I listed off before, like meat and fish, and eggs, and vegetables, and fruits, and some I do like starches like rice, oatmeal, some pastas, some sourdough breads, and things I love butter, who doesn't love butter.

1:31:00Of course, none of that stuff in excess olive oil. But if one looks at kind of that buffet of options, you realize you can get some high -quality amino acids. You can get some high -quality lipids. You probably want to get more of them from olive oil than from butter, but you can get the micronutrients you need provided those food sources are healthy. Now, contrast that with a highly processed diet or even a minimally processed diet. And you can get the taste, you can get the macronutrients, you can get the calories. But you don't, meaning the brain doesn't really have a sense of it, can't directly map taste calories, micronutrients on to one another.

1:31:42And so you can imagine that the neural circuits, and here I'm a little bit of hypothesizing slash conjecture, but that the neural circuits responsible for hunger and satiety would get immensely confused by what's in a highly processed food. Right? A Snickers bar, if you like sweets, tastes pretty good, but it's unclear what's in it, except sugar, except some, you know, it's got a certain Snickers bar taste, right? But if the circuits of the brain are really trying to drive us to get amino acids and micronutrients for bodily health and repair, well then highly processed and even moderately processed food is just got to be pure confusion.

1:32:22Sorry to go long here, but it reminds me of an idea I had once like imagine if you took a pill that greatly increased the level of dopamine, or epinephrine, acetocholine, and serotonin all at once, that's polypharmacology. And it might make you feel a certain way, maybe good, maybe bad. And then afterwards you'd probably have a bit of a crash from as the drug wore off, no doubt you would. But let's say you wanted more of that feeling, you wouldn't really know what to go look for because you don't know what was in it because it's polypharmacology.

1:32:56So foods that create a more pure experience of micronutrients amino acid content, calories and taste, those four things mapped to one another, that intuitively we can start to understand, oh I like this food and it's good for me. And this is enough of it. I don't know anyone who of reasonable size that eats like four rib -eye steaks, you know, they eat one. I'm sure there's some freaks out there that do that. But one, you know, even small piece of quality meat is very satiating. Yeah, you will self -regulate because the body, like every other animal in the world, is exquisitely designed to regulate hunger on a very intuitive level if we eat natural food.

1:33:41It's, you know, I think it's almost ridiculous to talk about calories and isolation because the reason we're eating more calories is because we're eating ultra -processed food. And so, but I love what you just said, Andrew, about the brain and the polypharmacy. I think that literally is, I've never heard that said. And I think it's like processed food is like polypharmacy of food. It is the definition of processed food, which I know you talked about with Rob Lustig, the Nova 4 criteria, is literally it's breaking down foods into these constituent parts that were never meant to be separated from each other, like the endosperm of a wheat kernel, separate from the brand and the, you know, the germ.

1:34:23And then take that and like a little science experiment, pair it up with all these other individual components and synthetic chemicals that are made in a factory and put them together to create this thing that the body, I truly think our insatiable hunger, again, we're eating ourselves to death in the United States. That's the reality. Our insatiable hunger and our chronic zy epidemic fundamentally is a lot of, it's, it's mass cellular confusion. And when you think about what chronic inflammation is, chronic inflammation is biochemical fear on the cellular level. Well, when you put this stuff into the body that's never seen before, obviously that's going to generate some confusion.

1:35:04And you know, you could, you could trace that back to what that really means with leaky gut and, you know, all the sorts of the real physiology of that. But there's a wonderful book that is called the end of cravings by Mark Schatz, or he also wrote the Dorito effect, but he talks a little bit about what you're talking about, which is to say, deal that processed food is actually the ultimate sort of food based variable reward. So in the way that it, in like things that, I mean, I'm speaking expert here, but things that the body can't predict what the outcome is going to be or going to kind of get you in that dopamine motivation pathway.

1:35:40And 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. So every time we eat tortilla and our brain is this incredible prediction machine. And as it's coming towards our mouth, we're predicting what the load is going to be. But we have no idea. Is it a Coke zero? Is it a diet Coke with Aspergain? 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.

1:36:17Whereas 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. But I think backing up a little bit, one one concept I have for food that really helps me is really thinking about the body's always trying to help me be satiated and trying to help reduce my cravings. I literally just have to give the body what it needs. I have to stimulate the body in a way that it will serve me and giving me satiety hormones to basically regulate my hunger.

1:36:59And again, with visuals, I think it's so helpful. I think about these cells lining our small intestine that literally have nutrient sensors, like and literal receptors on the cell membrane in the lumenol side of the gut that's facing all the food that are just sitting there like waiting to bind with these things in our food that will stimulate the cell to make the satiety hormone that poof effortly makes us not hungry gets rid of that grip of attachment to cravings that all of us are so plagued by. And like I think, you know, we have this intense conversation happening in society right now about GLP1 analogs and ozemic and minjarra and all these things, GLP1 agonists.

1:37:40But like, you know, we rarely talk about the fact that like we have nutrient sensing cells of the gut, the L cells of the gut that when stimulated appropriately will make GLP1. And when stimulated the way they want to be will secrete hordes of GLP1 for us. And so how do we actually think about just literally giving the body what it needs to stimulate the satiety hormones? And the process foods aren't giving us those things. You know, the things that are going to stimulate those cells, well, the things that will, I mean, this is kind of fascinating if you don't mind going down a little road talking.

1:38:13Yeah. Please. With the GLP1 conversation, I feel like so missing from the conversation is the idea that like from a first principles perspective, there's three ways our body could make more GLP1. We make more cells that make it, L cells of the gut. Each of those cells makes more GLP1. And importantly, we can also inhibit the inactivator of GLP1, which is an enzyme called DPP4. So GLP1 actually gets rapidly degraded by DPP4 in the body. So if we can figure out how to inhibit DPP4, we can raise our GLP1 levels. What is DPP4? It's an enzyme that breaks down GLP1. I think you said that and I missed that in politics.

1:38:55It's so fascinating. And so how often have you seen in the headlines, oh, here's some strategies to inhibit your DPP4. Never because Ozentvik is, you know, on track to be the highest -grossing met and human history. And just like we talked about in the beginning of the episode, the whole industry, this four trillion dollar 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 GLP1 from each L cell and then inhibit the breakdown of the inhibition of DPP4.

1:39:29For the first one, we know that short -chain fatty acids, which of course are the by -product 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 Saunemberg from Stanford on a world expert in gut microbiome. And he was a big proponent of based on work he's done with Kris Gardner and others at Stanford. So happens of ingesting one to three servings of low sugar fermented foods each day, things like sour cow, kimchi, again, low sugar varieties, probably best.

1:40:10Yeah, 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. And often costly too. And pretty costly. The sour croutes, you can actually make your own sour crout. Tim Ferris had a great recipe for this in the four hour chef. You have to be careful because you know that you can create some unhealthy ferment. You have to do it the way he describes. So check out the recipe it's online. Or you can buy sour crout and the brine's drinking the brine off the sour crout. Or off seems to be good for the gut. That's such a great point, which is that ultimately we want the short -term fatty acids, which is the the medicine that the microbiome are making for us through the microbial fermentation process.

1:40:53And 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 in fiber to short -chain fatty acids, which then we absorb. And then like you just said, in a fermented food, the bacteria in that food will be making short -chain fatty acids by fermenting the food in there. And then if we drink that, we're getting the short -chain fatty acids directly.

1:41:31So that's the kimchi, sour, crout, Greek yogurt, kavas, which I'm obsessed with, which is like low sugar canbucia. It's like made with fermenting beets, basically. That's good stuff. It's such good stuff. At miso, natto. So that's one. That has been shown to differentiate more L cells in the gut. We also know that people with type 2 diabetes have much fewer L cells in the gut. And it's hard to know what the causality is there. But I think 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.

1:42:08And 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 has been settled, but very high antioxidant component plant. When we look at actually stimulating more GLP1, you've talked about your Ramate, I think, having like a mild effect on GLP1. But there's actually a lot of other things in the literature. Protein, of course, very potently stimulates these nutrient receptor cells. And specifically like valine and glutamine seem to have a potent stimulatory effect on GLP1. So you're just going to find that in like meat and turkey and eggs and things like that.

1:42:53What are your thoughts on supplementing olglutamine? It's controversial. I know that some people do it in an effort to relieve leaky gut, but that's it. But there aren't any randomized control trials for that. So the, depending on one stance on what's required for kind of a threshold for for adopting something, you know, some people say that's crazy. Other people really swear by supplementing olglutamine. Maybe it's through this this route of increasing L cells that some of it got relief might exist. I guess we'd have to explore it. So that's speculative folks. So this is interesting. These are ways to increase the cells that then make GLP1.

1:43:30So fiber, prebiotic, probiotic fiber, and fermented. Antioxidants, lowering blood sugar, gin, saying. So those are kind of the L cell ones. The actual secretion of more GLP1, that one of the most potent ones and the study that looks at this, like the barographs are very clearly statistically significant. Lots of asterisks is actually thylacoids. So thylacoids. Tell me more about thylacoids. Thylacoids are so fascinating. Thylacoids are actually a structure in plants that are part of the chloroplasts. So, you know, chloroplasts, and this also is fascinating, as chloroplasts are basically the plant version of mitochondria, essentially.

1:44:09And thylacoids 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 five grams of straight thylacoid, over 12 weeks daily, it led to a significant increase in GLP1. And again, I don't remember the exact, it was two or three full tire secretion. So, this is in part, so that's a direct symmetry effect of the L cells. And so this equates to 3 .5 ounces of spinach a day, which is like nothing. So just getting those green. Ross spinach or cook spinach? I think, I actually, I don't think it actually, it might have said in the methods, but I would, I would imagine raw because you want to get those undenatured thylacoids in the gut.

1:44:56So just kind of another, actually thylacoids do a lot of other interesting stuff. They inhibit lipase in the gut. And so actually help more fat get down to the distal small bowel and promote satiety. So this is one of the reasons why you talk about, oh, the people who eat all these healthy foods in greens, they're less hungry. It's like, it's biochemistry. Like, there's stuff happening in there that is making the hunger signals go down through things like inhibiting lipase, you know, improving GLP1 secretion. So other things for GLP1 secretion, the thylacoids, also fibers have been shown, specific amino acids, so high protein foods, things that involve a lot of valine and glutamine, green tea, and specifically the, the ECGC that is one of the compounds in green tea.

1:45:47That's several things that are all in that like whole food, you know, basically things you would associate with a healthy diet, but we actually know they stimulate GLP1. So, you know, those are all things I try to include in my diet. And the last one is inhibition of DPP4. And that one, there's just actually, when you look at the research, there's some kind of random foods that tend to inhibit DPP4 black beans, Mexican oregano, other forms oregano, rosemary, guava, and I wrote this one down, because it's a word I hadn't seen very much before I started digging into this, but mericetin, which is found in berries, cranberries, and peppers, and, and Swiss chard.

1:46:24So all that is to say, ultimately, many of us are gripped by cravings. And the idea of have, you know, just sort of not being constantly driven to eat more, which I would argue that about 80 % of Americans are, feels really hard to overcome. But a lot of it is literally just communicating to yourselves in a clear way through food to help you be satiated. And the science can show us how to do this. And a lot of it comes down to eating, essentially what you were talking about, how you eat omnivorous protein, healthy sources with nutrient, you know, density, and lots of colorful fruits, vegetables, spices, herbs, things like that.

1:47:14So yeah. It's interesting, again, these aren't randomized control trials nor they peer -reviewed studies, but I have a few friends who have known for most of my life who really struggled with their weight, carried a lot of excess weight, and we're starting to suffer health issues in their, even their 30s, but in their 40s, I'm 48, so they're my peers, and so they're about that age range. And they've all done extremely well, meaning they lost a tremendous amount of body fat, are terrifically healthy now, by way of basically restricting their food intake to proteins, so fish and meat, eggs, fruits and vegetables.

1:47:58They 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, and what's interesting is all of them now seem to really enjoy eating foods in their more pure form, right? And I'm not somebody that like pushes on this on my friends, they just come to me and say, like, how do I lose 50 pounds without having to exercise it all off, you know, as the only source of weight loss, they all exercise as well, but it's just so daunting to try and lose, you know, 20, 30, 40 pounds, and to do so quickly and then to keep it off, because they've all had the experience of going on diet and then exercising a lot.

1:48:52The point here is that I really think there's something powerful about that relationship between taste, macronutrient value, micronutrient value, and satiety. I think there's really those powerful associations because the brain is such an associative machine. One thing that I should have said before, and I know most people are familiar with ozempic, and its commercial names are, I forget what the the... Ozempic is the commercial name, and runjaro, and wagovi, and yeah. Got it. Is that GLP1 acts more or less as an appetite suppressant? Right. Yeah. Powerful appetite suppressant. Yeah. So many millions of people are now taking GLP1 analogs, is that right?

1:49:36I think there were over 20 million prescription in the United States last year. Is it expensive? It's $20 ,000 per year. Does insurance cover it typically? Right now, insurance is covering it for indications, but there is a all -out assault from the pharmaceutical industry to essentially classify obesity as a genetic disease and a chronic disease in order to be able to feed this medication more into the insurance pathway and essentially get more taxpayer dollars to pay for this medication. And it is extremely expensive, and it's on track to be the highest grossing medication in human history because it's now being recommended for people with obesity, type -d 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.

1:50:36And I think really it's such a travesty based on the conversation we've had because what ozempic does not do in any way, shape, or form, is impact the toxic environment that we're living in that's hurting our mitochondria. Losing weight is different than improving mitochondrial function. And mitochondrial function is the root cause of basically every chronic illness and symptom that's torturing American lives today. And so in many ways, it represents like the ultimate bandaid for an environment that is not changing. And when you think about what we could do with $20 ,000 per year, and it's a weekly injection.

1:51:19So people will say, well, per person, like, oh, it's, and it's a medication that is intended to be taken for life because when people come off this medication, many people are gaining back all of the weight or even more weight afterwards. And then there's been conversations, Peter Tia's waiting on this about loss in lean mass, you know, part of the weight loss is disproportionately muscle. And so there's a lot of concerns about it above and beyond its ability to lower the number on the scale that we should all be very alert to because, you know, the reality is 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.

1:52:03And there is obviously no shot that can mitigate the multi -front assault on our biology that ultimately generates a body that's immensely profitable for those hundred specialties of healthcare. So, you know, we're living in this matrix in this game of, you know, a devil's bargain between a $4 trillion healthcare and pharmaceutical industry and a you know, the answer is found in a shot and we don't need to change anything about our lifestyle. But of course, you know, these simple habits that we're talking about eating real food, moving walking, etc. Getting out in the sunlight rapidly can increase our mitochondrial capacity.

1:52:44And, you know, are just the most disruptive thing that we can do, you know, in our culture today is is learn about metabolic health and improve it. And it's just interesting to see what's happening in the media with sort of the assaults against these empowering habits and very in favor of a medication like ozemic. And then when you trace, you know, unfortunately incentives there, a huge percentage of these outlets that cover, you know, ozemic is a miracle drug. Their bills are paid by Pharma, 60 % of mainstream media advertising budget is Pharma. And so, you know, I just, I just say that because I think it's a scandal that we give so much air time to these medications and not to simple metabolic habits that can make us feel, you know, so incredible and really change our core biology.

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

1:54:09At least not yet. Take a GLP analog like ozempic. Lose it some weight, probably lose it some muscle also. One would hope that that would give them the sense, okay, now I can move my body better. I'll start exercising eating better as well. I think that I have to imagine that there's a middle case condition where people are not just relying on pharmaceuticals and not just relying on behavioral routes to improve metabolic health, but can do both, right? I mean, that and one would hope they are if they're already taking these meds. Or is it the case that when people have a pillar and 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 in the podcast, like the FENFEN and then there was another one, I think even before that, that made people their temperature go up that you talk to that. Okay, yes, so the two, these are, I used to work on thermal regulation as an undergrad. So FENFEN was eventually banned because it caused some cardiac issues. I believe it was a stimulant for fluoramine to, sorry, it's not FENF fluoramine alone. It's a combination of things. It's what's called FENFEN.

1:55:19And then, Dynitrothenol, which was based on the observation that workers and ammunition's 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. 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. Dynitrothenol. And I think it has to do with sort of processing of the mitochondria. I think this is happening that the electron chains in mitochondria. So, free electron. Look it up. Excuse me.

1:56:03The bottom line here is that there have been plenty of drugs, mostly stimulants used to help people lose weight. Or that have acted directly on the mitochondria. It has not worked out well historically. It just hasn't. And I think that I'm not just going to lump, it's a different mechanism. So, I don't want to lump it in with past weight, lost drugs. However, if you look at the trends throughout history, the medicalization and pharmacology towards chronic issues has been an abject failure. I can't, 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 tattoo diabetes rates are going up. The more ozemic is being prescribed, obesity is going up. You know, this is on Wall Street. They're not, this is on track to be a blockbuster drug. And they're not assuming the rates of obesity are going to go down. That wouldn't actually make sense for the business model. I mean, these are being talked about at the JP Morgan Health Care conferences. Do you think they're thinking that this is going to plummet? No, like there are, I can't think of very many chronic conditions for which the explosion of the medication has reduced the frequency of the disease.

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. Like, they are inducing oxidative stress. They may help with the symptomatic management, but not actually reducing that trifecta that we talked about in the beginning. And so, why do we have reason to believe that medicalizing obesity and not actually getting at the root cause, which has to be impacted by multimodal gentle nudges in our daily life habits and environment that that's actually going to reduce the rates of the condition.

1:58:18So, no, that's very helpful. Okay, so I'll then return to the other question about temperature. What are some things that can do with temperature? And by the way, as I do this, I can't resist it 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. So, I'm going to try and eat them quietly.

1:58:53So, 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 and 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's some health effects. And I'm willing to weather the storm of of naysayers because more and more data keep emerging. Yeah. That's the case. Not all the data are spectacular. Yeah. One paper on this actually was just retracted. We need to do an update to an episode to not work for my lab. But I still think that there's a lot of really terrific work on deliberate cold exposure. What's the deal with temperature and mitochondria? So, no one has basically described this better than you. I feel like you're on your platform.

2:00:02But I think about it very, very simply. Throughout human history, humans have really in so many different parts of the world been exposed to hugely fluctuating temperatures. Like if you look at the Sahara desert or like a regular day in Colorado, it's like you can go from, let's talk about Sahara desert. You can go from 30 degrees to 110 degrees in the span of one day. And like even the concept of indoors is like a relatively new concept in human history for walls, you know, insulation, then central heating and cooling. That's like the last 50, 75 years in most homes. And so this idea ourselves have evolved to respond to big swings and temperature that very recently we have totally pulled away.

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, you know, food energy. Like there's, 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 like, you know, this data is hard to know if it's totally accurate, but like our population is cooling. And some, I think it was data to Stanford, actually, that was showing that like our temperature has gone down like 2 % or something like that in the last 100 years. And that fundamentally is mitochondria not working as well as they should research has shown we're making less ATP in a lot of ourselves. And that's, you know, 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 ATP, 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 you know, world in which our mitochondria under siege, I think it's a valuable often very inexpensive one that can we can use. Of course, it does not supplement or replace food, sleep, exercise, but I think it can be a very valuable tool to stimulate, you know, through that signal, to to basically make more heat.

2:02:53And you know, we know of course it can help. And again, the data, you know, is mixed, but like increase brown fat, which is like mitochondrial dense fat and have it do more work and whatnot. So ultimately, brown fat is mitochondrial dense fat. And we want to, you know, help promote that. So that's all he was called. And then on the heat side, you know, just fascinating how that's kind of acting to help metabolic health through the activation of the heat stock protein, 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, but you know, because we just can't, we can't avoid the food and, you know, the sleep and the movement, but I think it's a great tool that we can use. I love it. I'm, I will just point out that the reason the brown fat is brown at all is because of the density of mitochondria. Yeah. It's literally brown down the microscope. This is not the kind of fat that, well, I'm subcutaneous, although it, you know, it sits around the scapular 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.

2:03:59I think it's because people don't like it. And frankly, no one likes getting in it. The best part is getting out and how you feel afterwards. But I think it, nothing great 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 a, you know, a, essentially, more of a furnace, more, more, more brown fat. Anyway, we could go on and on. But I think it's yet another lever of autonomy in terms of taking control of one's health. As you said, not as critical as food intake and quality amount and maybe timing as well. Speaking of timing, what are your thoughts on fasting? And then, of course, movement and exercise. Yeah. 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, you know, we are diurnal organisms. So we kind of need to respect that. Like when we do that and we compress it in a moderate way, our metabolic health is better.

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, you know, a lot, maybe just consider compressing it into daytime hours, six to eight hour window.

2:07:23Yeah, for me, six is tough. Six is tough. The one meal per day thing is tough. I have friends like like Friedman that do the one meal per day thing. I end up eating so much food at that meal. I experience a lot of like mechanical distress. And typically later in the day, I think an eight to ten hour window has worked well for me most most days. I know as soon as we talk about intermittent fasting, which is what or time restricted feeding same thing, which is what we're talking about right now. Sure, somebody's going to call up the there's been a study that's been circulating about a massive increase in cardiovascular risk in people doing intermittent fasting in particular the six hour eating window.

2:08:01I just want to point out we're a study. As far as I know, I could be wrong, but as far as I know that study is still in abstract form, it's not yet peer reviewed. 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 and it may end up in a journal that you is barely worthy of a placemat.

2:08:44It might end up in a high tier or high quality journal, but it might not. So just because there was a quote -unquote a study done means very little, but it means especially little, maybe nothing until it's peer reviewed. Absolutely. In the methods were very poor in that study. It was a recall based study, I think, for two days of 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 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 with 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 that glucose, you're going to be turning on all the pathways with insulin to basically store it. And so it's strained for the body. And so I think giving the body times intentionally to allow insulin to come down and to allow glucose to come down, what that does is it generates metabolic flexibility.

2:10:10It 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 obesity rates in the country is because with the way the culture of eating right now, 11 eating events today, 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 -process food, about 70 % of the items on the shelves in the grocery store ultra -process food and those ultra -process foods are built on refined added sugars and refined added grains. So we're just, we very rarely give the body the opportunity to rest and move into fat burning. And that's where compressing the eating window can be valuable. Obviously, people have talked about this before, but fasting can be a stressor for the body, 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.

2:11:47I can tell if I've got too many other things going on, I haven't slept well, a lot of stress, I can tell that fasting's kind of making me jittery and not feel good versus if I'm really, if I have good capacity, I can feel that it's actually making me feel really incredible. And so tune in with your body, obviously. And you know, you can check your biomarkers if you have a CGM on, you can see what's happening in your glucose. If you have a ketone monitor, you can see what's happening in your ketones and really actually track, which I think makes fasting actually even even more fun. I'll mention one other piece of data that I think is actually really kind of fun as well with timing of eating.

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 9 .30. And the glucose and insulin responses for the same meal at 8 .30 p .m. were significantly higher than when eating at 9 .30 a .m. And so again, being for your buck, it appears that eating in that earlier part of the day when we're active and our chronobiology is set up for metabolism and activity. We have a lower glucose and insulin response. There's also some evidence that melatonin, which is secreted, you know, as we get closer to sleep, has somewhat of an effect on impairing our insulin sensitivity transiently.

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, a little bit more low carb. I would say throughout the day based on that data and what I've seen on my continuous glucose monitor, basically just higher spikes for the same meal later in the day. So why not just kind of move it up earlier? Very interesting. Something I'll definitely try. I tend to push my carbohydrates to a little bit later in the day for sake of sleep. Unless, of course, I've done resistance training, which I do three times, I aim to do three times a week.

2:13:45And post -resistance training, I try and get some starchy carbohydrate in me just to replenish glycogen. And that's then tends to reduce my carbohydrate craving later in the day. I love bread and butter, bread and olive oil pastas. And the other day I found this Argentine place and I love the steaks there, but they had a mnyoki that it took everything I had, every neural circuit that releases GABA in addition to my brain to not order three of those orders. It was so good. But you can look after the mnyoki. Yeah, sure. I'll allow myself to do your own things. I'm not super restrictive. But again, I tend to eat high quality foods.

2:14:19By the way, these blueberries are amazing. Then you figure out where you got those because they're just tangy enough. I'm doing everything I can to just not take the jar and funnel them into my mouth. Yeah, I think, 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 surprise me, certain foods tend to spike my my blood sugar.

2:15:02I'm quite a bit grapes. That shouldn't be surprising. Foods, food order was very powerful for me. I know that the date on food order a little bit mixed and it's controversial. But I like to eat like the French. I like some soup. Then I like my entree. I like the salad at the end. That turned out to have the steadiest and lowest rise in blood glucose for me. And then across time, I also found that I love hot sauna. I go so hot with the sauna that I've been accused by Rogan and other people. I'm going to turn myself into a brisket. But after the sauna, my blood sugar spikes presumably because I'm a bit dehydrated.

2:15:43And it's the concentration of blood glucose. Is that possible? Does that make sense? It does make sense. But also the heat can affect the accuracy of the sensor itself. Ah, okay. So that could be it too. But yeah, basically what it allowed me to do is make a few adjustments in terms of foods that I eliminated or 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. But by including olive oil and other things, it really blunts it. And of course here we're doing correlative anacidata.

2:16:20But for me, I felt far better when I included a bit more fat. And when the food order was adjusted the way I mentioned before, always including a little bit of fiber really helped. And that makes sense. Right. Slowly absorption of the food presumably. So I found that it was a very valuable experiment for me. Again, this isn't an advertisement. It just so happens I did this and really benefited from it. What are some other things that one can learn from continuous monitoring of blood glucose? What are some things to watch for that might signal a problem? And what are some fun things that one could do to explore and experiment?

2:16:57Because 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. And like you said, some of this data, it's like small studies, small groups of people. But for instance, adding fat and fiber to meals has a significant and repeatable impact in populations on lowering glucose response. Fat probably in some part due to slowing gastric emptying and actually slowing the digest in process. So the rise and the blood stream is going to slow down. And then fiber, both for that reason, but also because fiber can in a sense create like a mesh sort of blocking the absorption of some of the glucose that's in the meal.

2:17:37So literally kind of actually preventing you from absorbing all of the carbs. And we've actually seen that in the levels data set that the more fiber people include with their meals, we see essentially a direct relationship with lowering of their 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 kind of just helps you kind of get more from your meal. So what you can learn. So I think step one, the way I think about a glucose monitor, first of all, say the purpose of the glucose monitor is not to have to game the system and get flat glucose.

2:18:25The purpose of the glucose monitor is curiosity. It's to start to understand how essentially an MRI for how all of our different dietary and lifestyle strategies are creating this read out 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 like very helpful in actually reducing the confusion and the cognitive load of our choices. We know that keeping your blood sugar through the course of a lifetime in a low and healthy range.

2:19:02So I don't mean up and down spikes during the day, but keeping your blood sugar healthy throughout the course of your lifetime is probably the best thing we can do for longevity, staying insulin sensitive, staying out of the diabetic range. And so one thing that the glucose monitor does for us is just give us more awareness and agency until like what the trends of our glucose are over time, as opposed to a literally one data point snapshot once a year in the doctor's office, which is what the majority of us are used to. I really love the idea that people who are able to wear glucose monitors every now and again, maybe once a year, maybe more than once a year, they know what their glucose is.

2:19:45And so they're never going to walk into a doctor's office and have a bomb dropped on them about prediabetes to type 2 diabetes because you have the data, which is ultimately I hope the world that we can move towards for a lot of biomarkers. So you can see trends over time, which I think is very valuable. One thing that's fascinating in terms of early prediction of metabolic disease is that you can see how long it takes your glucose to come down after a meal. So in a normal healthy insulin sensitive body, even if the glucose goes way up, it should come way down very quickly because the insulin is binding to insulin receptors and the glucose is getting taken up and it'll lower.

2:20:23What is quickly over the course of it? It should be down by two hours, but from what I've actually seen in our like most insulin sensitive people and also in research that looks at young healthy populations, you should basically be spiking and coming down, spike about 45 minutes and come down hour and a half, 90 minutes to two hours. But if this is after sorry, after last bite, after last bite, although it's hard to kind of exactly know, but yeah, meal is over. I would say about 45 minutes to go up to the peak and then start coming down very quickly. Now, if you start to see that glucose is going up and then trailing very slowly back down to normal, maybe taking more than two hours, three hours, that is going to be one of those early indicators of potential insulin resistance.

2:21:10Your body's not clearing the glucose, but that's not a metric that we use in standard practice at all. And I've actually seen myself very insulin sensitive. My insulin is like 2 .5 and you know, if I don't sleep and I am stressed and I have been sitting, my glucose will take way longer to come down. I have become trans -inly insulin resistant. So I think that's just fascinating to see that. So looking what that ultimately the metric that we call that is area under the curve. You want a low area under the curve, AUC, after a glucose spike. So you want a spike and come down quickly. That's going to be if you shade the area under the curve, it's a small amount.

2:21:49If you go up and then trail off for two to three hours, that's going to be a lot of shading under that curve. And high AUC is associated with insulin resistance, basically. Another thing that you can see is essentially glycemic variability. And glycemic variability, GV, is a metric of how spiky your curves are. Facing paper out of Michael Schneider's lab at Stanford in 2018 called glucose types reveal new patterns of glucose dysregulation. Totally landmark study. But basically they put concliners glucose monitors on non -diabetic individuals who by standard criteria of diabetes do not have diabetes.

2:22:35And he showed that on a CGM, a continuous glucose monitor, you have these low variability people that are pretty much flat throughout the day with little teeny little teeny rolling hills after their meals. You have moderately spiky people and then you have very spiky people who are going up, down, up, down, up, down. When you correlate those different patterns of glycemic variability in non -diabetic people, you find that the spikier they are, the worst their biomarkers are, metabolically across the board, insulin, triglycerides, etc. So basically they're showing signs through variability of underlying dysfunction that you would never know from a standard test.

2:23:13Those are the people who I imagine are probably going to go on to develop diseases. And yet based on standard criteria, their doctors telling them that they're fine, that they're all the same. So he also showed in that study that non -diabetic individuals, when you have a CGM on, are going into the diabetic range and the prediabetic range, a fairly significant amount. And we would never know that if you weren't, if you weren't actually tracking like a movie of the glucose. So that's so glycemic variability, area into the curve, those are two things. Another really interesting thing you can know from a CGM is Dawn Effect.

2:23:47So 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. What's happening here is that the cortisol awakening response to actually get you to wake up and get out of bed, that cortisol can 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.

2:24:24So 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. But also if you imagine if you're dumping all that glucose from your liver and your cells aren't taking it up well, because you're insulin resistant, that 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.

2:25:00So 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. So those are kind of some of the looking at early predictors of metabolic dysfunction. More of the fun stuff is like actually just figuring out like how is food affecting your body? And this is where people really enjoy it. And like figure out like, oh my god, this food that I thought was healthy is actually not, you know, serving me.

2:25:36And 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 yet levels. His healthy snack, he worked in Venice, would be to go to moon juice and get, oh gosh, I don't want to throw moon juice under the bus here, but he would get like, they do, but he would get this green juice that was sweetened with dates and it was like $9. And this was like the healthy choice. And he saw the second he put on levels that it was causing a huge spike, like 50, 60, 70 points. And then he was crashing. And he was actually trying to make a good decision.

2:26:12So now he's 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 grabbing ghost stuff that isn't spiking his glucose. But I think it can help people figure out like which foods are doing what I want them to do and which maybe aren't. And same thing happened for so many of our members with oatmeal. Unfortunately, oatmeal instant oatmeal is one of the biggest spikers in our data set for breakfast. And a lot of people are making that choice because they think it's heart healthy. And in many people, it's actually causing a big glucose excursion and crash.

2:26:48And then in some other people, it's not. And so it's it's really helping with what are the sneaky spikers? And then where's the biochemical individuality? And there was a phenomenal paper out of Israel that from from Sal about seven years ago called personalized nutrition by prediction of glycemic responses. It made big waves. But it basically showed that you and I could eat the same handful of blueberries and have totally different glycemic responses. So the idea of glycemic index as like a certain amount of food with a certain amount of glucose causes a certain glucose rise, it kind of debunked that.

2:27:31And that matters because repeated sustained glycemic variability over time is not good for our health. We want to choose the foods or balance the foods that are going to keep us relatively more stable. So that that's that's very helpful just understanding your personal response to food. And then what are the lifestyle strategies you can use sleeping better, walking after meals, more resistance training, cold plunging, breath work that can actually serve to modulate the food environment to actually reduce the glucose spikes. And people find that all of those things can positively impact glucose spikes, especially the walks after the meals.

2:28:08But it's been fascinating to see a lot of women, especially like menopausal women in our community who find that their glucose patterns are getting worse because 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. That kind of creates a virtuous cycle. So so those are some of the big things. Those are big. Oh, 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, post -prandial hypoglycemia. A lot of people think they're dealing with hypoglycemia, when in fact what they're really dealing with is that they're spiking their glucose too high and then they're crashing. I see. And the paper showed that the extent of post -meal dips, the crash after the spike was predictive of 24 -hour energy intake and cravings for carbohydrates. And this makes sense. If you crash low, that is a signal to your body. We have to get our glucose back up and it will drive you to eat high energy foods, carbohydrate -rich foods and cravings.

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 downstream consequences. 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 even having too much bright light in a room while want to sleep at night, even dim light, which is, I don't want to scare people in the thing they have to sleep in complete darkness, although an eye mask can be great.

2:30:55Can alter morning blood glucose levels. I believe it was adults and kids as well. This is studying 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 last hour or two of sleep in the morning that resting blood glucose is altered. It's so interesting to think about what's going on in sleep. There's at least one paper that I'm aware of where they had people breathing into a tube during sleep to measure what sorts of metabolism they were undergoing.

2:31:32And it's interesting. During a full -night sleep, all of us seem to transition between different forms of metabolism. I'll send you this paper. It's really cool. And I'll put a link to it in the show note caption such that at one portion of the night, we're metabolites, we're relying more on, let's just call it sugars for a sake of simplicity. Other times we're more ketone dominant. There's a market shifts in metabolism throughout the night. It's almost like the brain and body 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.

2:32:07But 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 prep belong to a gym. It's like, and with the cold exposure thing, I always say, if anything, it'll save you money on the heating bill. So there's a literally potential negative cost there.

2:32:42I think levels in other CGMs are really interesting and valuable to experiment with. What sorts of other stuff is going to soon be monitored or in our blood. Because for instance, I would love to know continuous hormone levels, lipid levels, blood sugar levels. I mean, are we moving past just blood glucose? 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. You 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.

2:33:20So 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 like a metabolic comprehensive metabolic standpoint, different sensors for each not all in one. So I think we'll have to like polka dot ourselves if we're tracking all those things. And then Dexcom, which is the other main company that makes CGMs, has just announced they're coming out with an over the counter, non -prescription version of a CGM, CGM called the Stella later this year.

2:34:08So 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 dynamic system are just never going to really be able to give us a full picture on what's going on. And what we really want to be able to do to dig our way out of this healthcare crisis, I think, is is empowerment individually and understanding how this rapidly changing environment is affecting our own biology. So we can make the targeted choices to hopefully change the environment to be more conducive to cellular health and continuous monitoring is a closed loop biofeedback that can 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.

2:35:01So yeah, I think lots coming down the pipeline. Love it. Yeah. Let's talk a little bit about mindset. This is a really interesting topic that you include in your book. We've had guests come on and talk about growth, mindset, stress can be enhancing mindset. I'm big on mindset because I'm interested in how our cognitive reframing or cognitive framing can just change the way our biology works and vice versa, of course. But you talk about mindset in a certain context in one of the favorite passages around that that I really enjoyed was the relationship between trying to control everything and nature, you know, and how getting into nature itself can be valuable for us.

2:35:45So maybe touch a little bit on mindset if you will and yeah, what are your thoughts on nature literally getting out of doing this? 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 diabetes genetic effect. It literally causes our blood sugar to go up when we feel stress and that can be a fascinating unlock for people to realize I kind of feel like I'm okay right now, but my body is telling me something different. It's telling me that biochemically, I'm actually releasing energy stores from my liver, glucose, to fight some threat that, you know, I wasn't really aware of. So there's, 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 more than the powerhouses the cell, they actually are a part of the cell that is constantly tracking resources and threats and are basically modulating energy resources based on that. And the threats can be anything. They can be a virus. They can be, and this is all coordinated through this thing called the cell danger response. It can be a virus. It can be a toxin in the environment. It can be lack of micronutrients for the electron transport chain that it needs to do its function.

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 here every single thought that we're thinking through biochemistry. And when a cell and a mitochondria are getting the message that there is a threat or something to be afraid of, they are going to change metabolic function towards defense alarm threat response and away from repair homeostasis building essentially thriving. So, 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 hours 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 desperatualized, very uniquely death -fearing culture like you look at other cultures, Eastern, Indigenous, the Stoics, they all had intense curiosity about death. We talk about the cycles of life. There's this real engagement with it that we are so afraid of in the 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 in the culture. And I think that through all these things, Americans are getting crushed mindset and psychology wise. And that is a big, big trigger of our mitochondria, essentially diverting resources towards defense threat and alarm rather than homeostasis building repair. So again, it comes back to taking really honest stock of what are the true fear triggers in our lives across those and others and creating a sense of safety in our minds and bodies no matter what the external world looks like, which may mean putting boundaries up to, you know, the media doing the therapy, doing the different modalities, what I believe, and I talk about in the book, getting back to the question about nature is one of the best things that we can do is actually literally just go outside.

2:41:41And I, it sounds so simple, but one of the most astonishing stats I literally found in researching this entire book was that the average American is spending 93 .7 % of their time indoors. Wild 93 .7. That's in a car or in a building. So we are locked in these cages staring at fear inducing media and our mitochondria are like, what? Like what? I don't know where to channel my energy. It's just, it's short circuiting, I think. So many things happen when we go outside. As you know, I mean, even what the vision system is doing to our anxiety levels, we are getting sunlight, which of course for, for, you know, complex reasons is very helpful for a metabolic health separately.

2:42:30In trains are, you know, chronobiology and, you know, light, 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, we see, you know, spring to summer to fall to winter, we see the tides moving in and out, everything's in phases. And I think when we reflect and meditate on all the cycles and the polarities in nature, night and day, cold and hot, new moon, you know, quarter moon, full moon, you know, all these things.

2:43:24It's actually, it entrenched us on a subconscious and conscious level that there is a fundamental harmony and pattern to the world we're living in that is bigger than us and that is fundamentally good and beautiful. And we are locked inside of the four walls of our house. I think we get very scared, we get very controllable and the system wants it that way because when we are scared and when we are 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.

2:44:10And that's what drives us into all the dopamine loops, you know, the social media, the processed food, the porn, the gambling, the alcohol, all of it. It's all to ameliorate, I think ultimately fear. And I think, yeah, I think by actually really just spending a lot more time, trying to get that 93 .7 % down to like 50%, spend as much time as you can outside, we know that people who spend more time outside are metabolically healthier. And I think it's for pleatropic 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.

2:44:54And that has a profoundly soothing effect on our psychology and the sense of scarcity that drives a lot of the decisions that actually make us unhealthy. It's fundamentally rooted in in scarcity. And I think also when we realize we are part of nature, again, going back to that Taoist statement, we're a process, not an entity, realizing like, you know, all the trees around us and we take that walk even in a city, we see all the trees, all those plants, all those leaves are making the oxygen that process that literally let us do oxyphus for allation. And that sun and that leaf on the tree, the sun's energy is literally being stored in the carbon carbon bonds that the plants are generating 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.

2:45:51And 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 I think a lot of people will find that their health gets a lot better if they spend radically more time outdoors. And I think a lot of people might say, like, can't I work on a computer? And I'm like, you know, Rome is burning like we're sick as hell right now.

2:46:30We need to get creative. Like move your computer outside, take a walking meeting, open your mail outdoors, chop your vegetables on your balcony at your apartment. Like we 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 being in the conversation, that's fundamentally what's wrong with the healthcare system.

2:47:17It's silos. And we have siled ourselves from all of the life giving things in our environment. And that has ultimately led us to be very, very, very sick. And we've 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 those 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 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's said back to nature, the only truth. And I asked him when he meant by that. And you know, because Rick can be a little bit cryptic sometimes, not always, but sometimes. And what he was saying is, you know, it's a real thing. You know, you can immediately feel the connectedness between the human experience and life of other types, plants, animals, you know, sunlight, the circadian rhythms and the rhythms of the light and dark, because they impact us so powerfully.

2:48:38I mean, if there were ever a force in the world that impacts how we feel, it's the circadian rhythm, it's the rising and setting of the sun, it's on the impact of light and dark. And then all the other things that you talked about today, I can't help but reflect on kind of your take on kind of 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.

2:49:16And 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, 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 and nearsightedness.

2:49:50This is independent of all the other effects of circadian rhythms, et cetera. Anyway, and on and on. So I second and third and and here, here, all the statements you made before. I also just have to say I really appreciate how you are able to tackle the cellar 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 we've 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.

2:50:39Not 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. It'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, I'm going to do what I see as best for the greater good, in terms of giving people tools, giving people a sense of agency and autonomy to take control of their health.

2:51:35This isn't 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 need it and we appreciate it. So 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.

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