March 2, 2024
Metabolic Dysfunction and Lessons From the Largest Glucose Dataset in the World with Dr. Casey Means

Child: Welcome to my Mommy’s podcast.

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Katie: Hello and welcome to The Wellness Mama Podcast. I’m Katie from wellnessmama.com, and this episode is all about metabolic dysfunction as the root cause of nearly all diseases and lessons from the largest glucose data set in the world. And I’m back with return guest Dr. Casey Means, who is a Stanford-trained physician and the CMO and Co-Founder of the metabolic health company called Levels. Her mission is to maximize human potential and reverse the epidemic of preventable chronic disease by empowering individuals with tech-enabled tools that can inform smart, personalized, and sustainable dietary and lifestyle choices. Her perspective has been featured in everything from Wall Street Journal to the New York Times and much, much more.

And we get to go deep on this topic today. She really explains super comprehensively what metabolic dysfunction is and the markers that go into that. The five most effective and least expensive tests you can get to get a good picture of what’s going on metabolically in your body, how glucose is a good metric here as well, and how to use it to your advantage, and so much more. We talk about very actionable takeaways that everyone can do even without the data to start improving metabolic health, as well as what to do if you are able to get more personalized data on your own physicality and what’s going on and how to use that to your advantage. She is so well-spoken and such a wealth of knowledge. And like I said, we get to go deep on a lot of this today. So, without any further wait, let’s jump in with Dr. Casey Means. Casey, welcome back. Thanks for returning to the podcast.

Casey: I am so happy to be here. Thanks for having me, Katie.

Katie: Well, I will link to our first conversation for anyone who hasn’t heard it already, but I know we got to go deep on the topic of glucose, especially in blood glucose, what we can learn from it. And I’m excited to build on that conversation with all of the new information available. I know you guys have a tremendous dataset that I believe is the biggest in the world on this topic. And there’s so much we can use this actionable data to really impact our lives in a positive way. To start off, I know that one of the questions I asked in prep for interviews is if you were going to give a TED Talk in a week, what would it be on? And I love your answer because you talked about how underpowered cells, or basically metabolic dysfunction, is often the root of nearly all disease in the modern world. And I know this is why you’re so passionate about the work that you’re doing with Levels, but I would love to use that as a jumping-in point for our conversation today. If you could explain a little background by what you mean by that, and maybe some of the factors that come into play with metabolic dysfunction and how that can exhibit in different ways in our lives.

Casey: Yeah, absolutely. So, the message that I really… My goal in life really to get across to people is this idea that so many of the things we’re struggling with in our world today, in the modern industrial Western world, so many of the pain points facing our lives and the symptoms that we have that then lead to more serious conditions down the road are fundamentally all linked by the same physiology, which is this idea of underpowered cells, essentially metabolic dysfunction.

 

We’ve been hearing a lot more about this concept of metabolism and metabolic health, metabolic dysfunction, blood sugar control over the last few years, and it’s for good reason. And it’s because what we’re really learning is that the key causes of morbidity and mortality in the United States in adults for sure, but even now more so in children, is metabolic dysfunction. And so, metabolism is how we convert food energy to cellular energy in our bodies. We have 37 plus trillion cells in our body, and all of these trillions of cells every second together are doing trillions and trillions of chemical reactions. And basically, our life and our health is the bubbling up of all of these chemical reactions. And all of them basically have to be paid for. All these chemical reactions have to be paid for with cellular energy.

And zooming back to high school biology, that cellular energy is ATP. It’s this molecule that basically is how we pay for all these cellular reactions. And that energy, that cellular energy, is made from food being converted to cellular energy. And this concept of metabolic dysfunction basically is that we’re having a problem right now in our bodies converting that food energy to cellular energy, which means that we basically have underpowered cells. The reason that’s the root of so many conditions that we see today that sometimes seem different, like it’s sometimes, you know, it’s confusing to be like, well, how is Alzheimer’s dementia fundamentally the same or similar to type 2 diabetes or infertility or erectile dysfunction or stroke or heart disease or retinopathy or chronic kidney disease or chronic liver disease or gout or depression or anxiety. Well, the reality is all those conditions we know now are either caused by or accelerated by underpowered cells metabolic dysfunction. So, the reason for this is that we have over 200 cell types in our body. And what’s interesting is that all those cells, of course, came from one cell, a fertilized embryo, and turned into 200 different cell types. And that’s cell types in our eyes, cell types in our brains, cell types in our blood vessels, there’s all these different cells, but they all need energy to function properly. And so, when you have a fundamental problem happening all over the body, a really core fundamental physiologic issue like metabolic dysfunction, essentially the problem in converting food energy to cellular energy, it can look like almost anything depending on what cell type it’s showing up in. So, if it’s happening in a blood vessel, it could look like a blood vessel related issue like heart disease or stroke. If it’s happening in a brain cell, depending on what type of brain cell that is, it could look like Alzheimer’s dementia, fibromyalgia, depression, anxiety, migraine, all conditions we know are linked to metabolic dysfunction. If it’s happening in ovarian theca cell, it could look like polycystic ovarian syndrome, the leading cause of infertility in the United States, which is a metabolic disease. If it’s happening in a blood vessel of a penis, it could look like erectile dysfunction. So basically, it’s a core physiology, a disturbance showing up in all these different cell types, looking like all these different diseases. But what we fundamentally need to realize is that those are branches of the same trunk. And in medicine in America today, we have to start treating the trunk of the tree as opposed to what we are doing right now, which is essentially playing whack-a-mole with all these different branches. And we’re not really getting very far.

And so, we’re dealing with this massive issue right now in the United States where people, Americans, are getting sicker every year. Chronic disease rates are going up for almost every major disease every year. And this is in spite of the fact that we are spending more money on healthcare every year as individuals and as a country. We’re spending over $4 trillion on healthcare every year. That number is astronomical. It’s 20% of the largest GDP in the entire world in human history. And as we spend more, disease rates are going up, and life expectancy is going down. So that is the definition of it, basically an ineffective approach and an unsustainable approach. And so, my real thesis that I feel that is really my purpose to share and why it would be my TED Talk is because I think the reason we’re seeing those dynamics is because we’re fundamentally approaching the wrong problem. We’re fundamentally approaching each disease as if it’s a separate siloed thing when really needing to focus on the root cause and the thing that connects these diseases, which is metabolic dysfunction.

 

And it’s something that, up until recently, we haven’t really been able, we haven’t really known it because the science has come a long way over the past 50 to 100 years. We used to be able to characterize diseases based on the symptoms that emerge. And of course, if you’re looking at symptoms as a way to define disease, yes, liver disease looks different than Alzheimer’s disease, and that looks different than gout. So, of course, we treat it differently. But now through genomics and cell signaling analysis and proteomics and all these things that we’ve kind of, we now are able to really see inside the cell more on a research level. We now know that there’s actually this core physiology that’s leading to a lot of these modern diseases. And we need to basically modernize the way that we treat based on that understanding. But it’s pretty widely known that it takes almost 20 years for research understanding to make it into clinical practice. And we’re in that messy middle right now where the science is better understood, but we’re not treating that way. We’re still treating reactively the symptoms, and that needs to change. So, patients, I think, need to really empower themselves to understand this unifying metabolic theory of disease and work to both understand and improve their metabolism so that they can have their best possible health and thrive.

Katie: Yeah, I agree. It’s so important. And this change that we’re seeing in healthcare and how people, like you mentioned, we’re getting sicker each year despite putting more money resources toward this, despite increasing awareness even in some ways about this. And for me, reading the statistic that, for the first time in two centuries, the current generation of children will have a shorter life expectancy than their parents was so staggering. That was a large part of why I started with Wellness Mama and why I’ve been in this world for 15 years now is because that stat to me is unacceptable for our kids. And I feel like the work you guys are doing is also very impactful in helping change that statistic, especially now with, as we talked about in our first episode, there is better access to things like wearable data, to understanding our glucose, to being able to run labs, even if we don’t have a doctor who’s perfectly aligned in our area. There’s so much access, but also that can become overwhelming when you get data but you don’t necessarily know how to make it actionable. So, I love that you guys are putting all these pieces in place to make data really actionable for people. And I’d love to delve into that because I know you’re also now able to look at biomarkers in a very specific way in ways that are very impactful, specifically when paired with glucose to create measurable changes in people. So, I would love for you to break down at what you’re finding on the biomarker level and what people can learn from that data that they’re able to now get individually.

Casey: Absolutely. So, you know, our mission at Levels is to reverse the metabolic disease epidemic. And that’s why we started the company. Our real belief is that to reverse this monumental trend we’re seeing in metabolic dysfunction, step one is people need to understand their own level of metabolic health, and then they have to understand how to improve it. And unfortunately, a lot of that’s not coming from the doctors for the reasons we talked about. We’re just behind. An unbelievable statistic is that, but that has essentially been shown in two independent research studies over the past four years, is that over 90% of American adults now have at least one biomarker of metabolic dysfunction. That was 88% about five years ago. And then, as of research from about a year ago, that’s gone up to 93.2%. And so, this is not a fringe issue. This is affecting almost everyone. What is so, I think, important for every person is to figure out if they have any biomarkers of metabolic dysfunction that they need to be aware of. And so, what we’re doing at Levels is aiming to democratize access to that data because it can be sometimes feel like pulling teeth within the healthcare system to try and get scraps of information. But my belief is really that everyone walking around should be able to say with certitude, I am or I’m not metabolically healthy, and I know what I need to do in terms of my diet and lifestyle to work on this and to get this in the right direction.

So, we do this in two ways at Levels, both of which I think are really important and which I hope the healthcare system will adopt as part of mainstream. One is blood-based biomarkers. So, these are single time point measurements that get drawn from your blood that basically tell you a very clear snapshot of a pillar moment in time, this is how I’m doing with metabolic health. And then the second piece of information that we give access to is continuous glucose monitoring. So that’s a sensor that you wear on the back of your arm that tells you actually, 24 hours a day, seven days a week, what’s happening with your blood sugar levels. And the blood sugar levels are a great real-time biomarker because they are a readout of how your metabolic health is, because if your metabolic health is dysfunctional, if your cells are having difficulty basically with that food-to-cellular energy conversion process, then what’s going to happen is that the cell is essentially going to block glucose from coming into it because it’s essentially overburdened. It can’t do that process efficiently of converting food energy like sugar to ATP. So, the cell blocks the entry of glucose, of sugar into the cell. That’s insulin resistance. And blood sugar levels will rise.

And so, blood sugar is this amazing biomarker that can tell us like a readout of whether there’s problems with metabolism in the body. And by tracking glucose in real-time in this more continuous movie-like way, you can start to see which foods and which lifestyle habits are either causing big swings and fluctuation in glucose or keeping it more stable. And ultimately, we want to keep it more stable and in a low and healthy range because that’s a sign that metabolic health is being supported. And so, combining these pillar blood-based biomarkers to give you a sense of this is how I’m doing overall in terms of my reading the tea leaves of metabolic health with my blood-based biomarkers. And then a real-time tool like a glucose monitor that’s giving you real-time biofeedback on individual decision-making to move in the right direction. Those two together, I think, are essentially transformational in both knowing where you stand and knowing how to improve.

So, in terms of blood-based biomarkers, there’s lots of different tests that can give you like a clue of metabolic health. The way I look at it is that there’s probably like eight to twelve tests that together a really seasoned metabolic health-focused doctor could look at all of them in combination and again, like read the tea leaves and sort of, so I’d say like that list would be fasting glucose, hemoglobin A1C, fasting insulin, triglycerides, HDL cholesterol, uric acid, ApoB, hs-CRP, an inflammatory marker, and certainly liver function tests. So, like AST and ALT. And there’s another test I really like called GGT, which is a liver function test that actually tells you about oxidative stress. So, if you can give me, like, and then having blood pressure, not a blood test, but blood pressure and waist circumference as well, those can give you another sense. But those 10 tests or so together, if you have them all and can look at all of them together, you can pretty much say whether someone’s got a problem with metabolism or not. What we did at Levels is we took five of those tests, which is insulin, ApoB, triglycerides, uric acid, and hemoglobin A1C, and we worked with our medical advisory board to say like, okay, with these five tests, you can get a really clear signal of like, whether there’s problems with metabolism. And I’m happy to talk through the tests like briefly individually if that would be helpful.

Katie: Yeah, let’s do that briefly because I would guess most people have heard of those tests, or at least most of them. But I think the relevance to metabolic health is really important to highlight. And some of them are not common on a lot of just panels that someone perhaps has had run before by a doctor.

Casey: Yeah, yeah. So, I’ll start with fasting insulin. So fasting insulin, I would say, is probably the most important metabolic health you can get. If someone said you have to get one test, I would say it would be fasting insulin. The reason for that, so insulin is the hormone that is released when blood sugar rises. Insulin basically binds to the surface of a cell to the insulin receptor and then allows glucose to enter the cell so that it can be processed through the mitochondria into energy. If there is excess, that glucose will often be stored as fat. We talked a little bit about this, but when the cell is overburdened, and the cell has metabolic dysfunction, which typically means the mitochondria is struggling to keep up with the influx of glucose and convert it to energy, the cell will put a block up called insulin resistance, which essentially blocks that insulin signal from allowing glucose into the cell because the cell is overburdened. The cell can’t process more of that glucose, so it blocks it from coming in, and that glucose will then rise in the bloodstream.

So, the reason fasting insulin is such a valuable test is because it’s essentially showing you from a really early stage that the cells are overburdened. There’s probably mitochondrial dysfunction going on. That metabolic conversion process is not working properly, and the cell is putting a block up to glucose entering. The way the body responds very quickly is by releasing more insulin into the body to try and overcome that block. And that looks like rising fasting insulin on a blood test. And the reason I think that’s actually even more valuable than testing a fasting glucose level, the blood sugar, is because the body actually, in releasing that excess insulin to overcome insulin resistance, it can actually overcompensate for a long time. And by pumping out lots of excess insulin, it can actually force the cell to push the glucose into the cell, even though the cell’s basically saying, we don’t want it, we can’t handle it. And there’s been interesting research showing that insulin resistance can be brewing in the body, and fasting insulin can be rising for over 10 years before fasting glucose rises. And so that’s a time of compensation where the body is basically churning out more of this hormone, forcing the glucose into the cell before you actually see a change in the glucose levels. So that’s a window where we could catch early insulin resistance where the fasting glucose test is not going to pick it up. Unfortunately, we do not test fasting insulin in our conventional medical practice. It’s a test you have to really request specially or get outside the system. And there’s a lot of reason for this, but it’s one of, I think, the biggest blind spots in medicine right now. We’ve got a situation where 50% of American adults now have pre-diabetes or type 2 diabetes, which are both conditions of insulin resistance. And we’re not testing for the earliest marker of insulin resistance. It’s so, so, so strange. So that’s one that I would say ask your doctor for it or get it through a special lab outside the system. It’s very important.

The range that, then there’s a second issue, which is that even if you get the test, a lot of the labs will report these ranges that are really lenient. And they’ll basically say on a lab slip that anything less than 25 milli use per milliliter is considered normal for a fasting insulin. But based on our best assessment of the research and coordinating with our amazing advisory board of metabolic experts, it actually appears that a fasting insulin of about two to six is optimal. And really when you start getting above like six milli use per milliliter, risk starts going up. So first, you got to get the test, then you’ve got to figure out how to interpret the test in a little bit of a tighter range. But if you can see that your fasting insulin is below that six range, in the two to six range, that’s a really good sign that your cells are metabolically happy, your body’s not churning out excess insulin due to insulin resistance. And it’s just a really, really valuable signal that your body is working properly metabolically. So that’s fasting insulin.

Another amazing test that goes hand in hand with that, which is part of our five biomarkers that we’ve chosen as triglycerides. So, triglycerides is a type of fat in the blood. It’s both a storage form of fat, and it’ll be found in the bloodstream that is created when excess glucose is converted to fat. So, the body doesn’t want just tons and tons of extra glucose floating around. It needs to put the excess glucose somewhere so it can be converted to triglycerides and stored in fat cells or found in circulation. And so, triglycerides is another sign that there’s some problem with how the body is converting food energy to ATP and it’s trying to put it somewhere. So, it puts it so if you start seeing an elevated fasting insulin and an elevated triglycerides, you’re starting to see a signal that the body’s overwhelmed and it’s not processing this energy properly.

Hemoglobin A1C is also a really valuable test because this is actually a snapshot of more of like a long-term picture of how glucose levels have been. So, hemoglobin A1C is referring to hemoglobin, which is, of course, part of the red blood cell that carries oxygen. How much of that molecule in the blood has sugar stuck to it basically? So, glycation is the process of sugar sticking to different molecules in the body. And when concentrations of blood sugar are high, they’re going to stick to things more. And we do not want sugar to stick to things in the body. It basically creates like rusting of the body. And so, hemoglobin A1C is essentially a percentage of hemoglobin molecules in the body that have sugar stuck to them. And we don’t want sugar stuck to anything, really. So glycated hemoglobin. And so that’s expressed as a percentage. The standard ranges say that we want our percentage to be less than 5.7% glycated hemoglobin. That’s the normal range. Anything above that is considered pre-diabetic. What we actually probably want optimally is between about 5 and 5.4% of glycated hemoglobin. That’s probably the healthiest range. And so, because red blood cells stick around in the blood for about 90 to 120 days, this percentage actually gives us a long-term snapshot of average glucose levels over the course of 90 to 120 days. That’s quite useful. It doesn’t give us much of a sense of what the fluctuations in glucose are day-to-day. That’s what a continuous glucose monitor would tell you. But it gives you just like a global sense of how much sugar has been sitting in my bloodstream. So, we want that percentage to be lower.

ApoB is the fourth test that we do. And this is a really interesting test. It’s part of what we call an advanced cholesterol marker. It’s not typically tested in standard practice. But everyone’s probably familiar with the concept of LDL cholesterol, which sometimes we call bad cholesterol. But there’s actually, what we really care about is how much cholesterol is floating around the bloodstream that we know can contribute to heart disease or plaques or blockages in the blood vessels. And that’s actually more than just LDL. First of all, there’s different types of LDL, some that are more likely to promote heart disease and blockages than others. And then there’s these other molecules like intermediate density LDL and VLDL, very low-density LDL. And so, there’s these different particles in the bloodstream that we just don’t talk about in our standard cholesterol panel. ApoB is actually a protein that wraps around these cholesterol particles when they are floating through the bloodstream. And ApoB is the specific protein that happens to be on all the heart disease-promoting particles. So, it’ll be on IDL particles or LDL particles. And so, what it does is it basically gives you a more complete picture of how many particles in the bloodstream are atherogenic or basically pro-heart disease. And so, some doctors are favoring ApoB as a more precise test of how many of the true bad cholesterol are in the bloodstream and maybe a better signal than LDL. So that’s why we included it on our panel as opposed to just LDL cholesterol because it’s more all-encompassing for other types of bad cholesterol.

And then the last one is uric acid. Uric acid is a really interesting test. We often hear of it in relation to gout, but it is actually so much more broadly relevant than just for people who may or may not suffer from gout. It’s actually a very important cardiac and overall metabolic marker. And uric acid can be raised in several different mechanisms. One is actually a by-product of fructose metabolism. So, we are eating astronomically more fructose as one of our forms of sugars in our diet now than we ever were in history. High fructose corn syrup was invented in the 1970s. And since then, people are eating about 3000% more fructose than we were prior to the invention of high fructose corn syrup. So, we’ve just had this astronomical rise in this type of sugar in the body, which is causing huge burdening to our systems. And when fructose is broken down by our cells, one of the byproducts is uric acid. Uric acid can then go on to cause problems in our cells by actually damaging our mitochondria and promote cardiovascular problems through several different mechanisms. So uric acid is a signal of excess fructose in the bloodstream, which we know is just deeply metabolically damaging. It also can be increased by what are called purine-rich foods. And so, these include animal products like meat, beer, and certain shellfish. And so, excesses in some of these things can also lead to increase in uric acid. And then alcohol generally can lead to increases in uric acid. But I’d say, generally speaking, of the things that are contributing to high uric acid in the average American, I’d say that the huge consumption of fructose in the form of liquid sugars and sodas, energy drinks, frappuccinos, processed foods, fructose is now literally everywhere. And so that’s a big contributor to uric acid. So that’s a sign on a lab test that the diet really needs to be like thoughtfully cleaned up. And it’s one that can change rapidly with adjustments in diet.

So those five tests together can give us a real signal of how things are going metabolically in the body. And I would say that, these are good to know like every four months or so, every quarter basically if you can, because if you are, first of all, if you’re staying in the optimal range for all of these tests, it’s a great sign that your cells are powered properly and the diet that you’ve chosen and the lifestyle plan that you’re following is like working well. It’s a great confirmatory signal that whatever plan you’re on, it’s working. And that’s really reassuring. I think so many of us are so confused about, am I eating the right diet? Should I be plant-based? Should I be carnivore? Should I be omnivorous? Like, should I do this plan? And it can be so overwhelming. And what I say is, just test, like test your metabolic biomarkers. And if they’re in a great and healthy range and you’re feeling good, you can feel confident that what you’re doing is working. And if they aren’t in an optimal range, then that’s a great starting point to make some adjustments and then retest in a few months. And if they’re not moving in the right direction, then you probably need to change your plan again. Like it’s really that simple. I am at the point where I refuse to argue about dietary dogma or this, because everyone’s different. And really you just need to know what’s going on in your own body and then make consistent tweaks and follow them over the course of a few and do them for a few months and then retest. And it’s really as simple as, is it getting better? Is it getting worse? Or is it staying the same? And based on that information, you can make additional tweaks. So that’s why I think testing like this is so valuable. And you can do all these tests for $99 and have a lot of really helpful information about where you stand. So those are the five that I think are really, really critical to know in every person.

Katie: And I love this because I say often on here, at the end of the day, we are each our own primary healthcare provider, and we can work with doctors and practitioners, but that responsibility still lies within us. And I feel like tools like this help us to have better data and better access in making decisions that are aligned in becoming our own primary healthcare provider. And I think, like I said, this data is invaluable, and of course, is very far reaching. Like you explained with the labs, these aren’t just single markers that tell you one thing. These are very far-ranging and can give you insight into lots of things happening within your body. And I know many of our listeners are women and moms especially. And I know that another area this can show up is in the hormone realm, that there can be an impact with metabolic dysfunction and hormone regulation. And certainly, that would be applicable in times like pregnancy and postpartum, but also, for many people listening, the perimenopause and menopause age is a big area of shift. And as you talked about those biomarkers, I know, for instance, that women’s cardiovascular disease risk rises when they go through menopause and that many of those shifts can lead to other things in the body as well. So, I would love to speak for a minute to the hormone side of that and how these markers come into play with fertility, with hormones, and how, of course, that relates to how we look and feel as well.

Casey: Absolutely. Yeah, I think that it’s so amazing. You just alluded to this fact about that cardiovascular disease goes up for women after menopause. And I think that this is another one of the biggest blind spots in medicine. Heart disease is the number one killer for women in the United States, and it’s a metabolic disease. You know, women are going to, after menopause, women basically start to outpace men on a lot of the metabolic diseases. So that’s like obesity, type 2 diabetes, heart disease, and Alzheimer’s dementia. And yet, this is not a word or a topic that gets brought up in these doctors’ appointments around menopause, or even in the 30s and 40s when you’re preparing for this time, when estrogen is going to drop, and that’s going to put you at much higher metabolic risk. And so, I’m just so grateful for platforms like yours that are talking about a lot of these things because we’re just not getting it from the mainstream.

So, starting, let’s say, in the 20s and 30s in the fertility conversation, it is so incredible how much it’s linked to metabolic health. The leading cause of infertility in the United States is polycystic ovarian syndrome. And polycystic ovarian syndrome, what we understand is that it’s very much rooted in metabolic dysfunction. It actually, the NIH in 2012 was going to change the name of PCOS to multi-system, a multi-system metabolic endocrine disorder. And they didn’t change it. And I think it actually would have been positive to change the name because not many people like polycystic ovarian syndrome, it’s hard to know what that means. But, like really calling it what it is, which is like a metabolic hormonal disorder, like really helps people figure out like where they need to approach. So, when insulin levels are high in the body, and we will talk about why it would be because of insulin resistance, that insulin actually signals a cell in the ovary called the theca cells of the ovary to produce more testosterone. So, like androgens and what we typically think of as male hormones. And so, when insulin stimulates the ovary to produce more testosterone, that really disturbs the delicate balance between testosterone, estrogen, progesterone, all the sex hormones that are so finely tuned. So, this, of course, impacts menstruation, it impacts ovulation, it impacts a lot of other things in the body too, like promoting acne and midline obesity and hair growth, things that you might what’s called hirsutism, which is essentially masculinizing features and things like that.

So, there’s all these things that trickle down from fundamentally hyperinsulinemia, high insulin levels. So, there’s been some amazing research that shows that like 12-week interventions with women that are mostly focused on dietary and lifestyle interventions that focus on really getting the insulin levels down, so like really high quality, low glycemic diet patterns over the course of 12 weeks, can totally transform the hormone balance. You get the insulin down, you get the stimulation of the testosterone down, and a lot of the other hormones fall into place, symptoms decline, periods become more regular. So, there’s a lot of hope here, and the cause of the high insulin levels in a lot of these women, it’s multifactorial. There seems to be a genetic component, there’s just living in America, it puts us in an uphill battle from the lifestyle perspective because of the way that our food culture is, but it’s multifactorial, genetics, lifestyle, all these things, but regardless of how much it’s weighted towards genetics or lifestyle or whatever, it still appears that these interventions focused on getting insulin levels down really, really help. So that’s really positive. But by some studies, up to 26% of women globally of childbearing age are dealing with PCOS. So this is not a tiny issue.

And then, as you get towards those perimenopausal years, there’s really interesting research showing that basically menopausal symptoms also correlate with metabolic dysfunction. So, menopausal symptoms like hot flashes at night and sleep disturbances and a lot of these things that really impact quality of life, mood. There’s been quite a bit of research showing that those really correlate in lockstep with degree of essentially blood sugar dysregulation. So, whether that’s a cause or effect, it’s not fully understood like the causality, but there seems to be a clear trend of the worse the menopausal symptoms are, the worse the metabolic health is. And if we can keep the blood sugar levels down and keep the metabolic health in check, the idea would be that this could potentially possibly in fact impact menopausal symptoms, although a lot more research needs to be done with that. But, you know, whether a blood sugar spike and crash can trigger vasomotor symptoms like hot flash, like there’s some research to suggest that there might be a link there.

So certainly, any intervention focused on keeping blood sugar in a lower and healthier range, keeping it more stable, could be a potential adjunctive modality to keep those symptoms more in check. And Dr. Sara Gottfried wrote an amazing book called Women, Food, and Hormones that talks a lot about this and essentially how to really prep for menopause by becoming as metabolically healthy as possible to hopefully ease some of the symptoms that can be so difficult.

Women after menopause, like we talked about earlier, kind of go off a metabolic cliff. Estrogen tends to be protective when it comes to metabolic health. And so, when that drops rapidly, insulin resistance does go up. And so, I’m 36 now, and a lot of how I think about the next 10, 15 years for me is thinking about how to essentially get myself into the best shape possible before going into that transition because no matter what, no matter who you are, there’s going to be a hit that happens when you lose that estrogen. So that means, making sure my insulin sensitivity is really good through diet, through lifestyle. It means resistance training now because we lose that muscle mass basically every year starting in our mid-30s, muscle mass naturally goes down. And muscle is one of our most protective things against basically metabolic dysfunction because muscle is like a huge blood sugar sink. It takes up and uses glucose, takes it out of the bloodstream. And so, it really helps with insulin resistance. So, if there’s one thing I would say to women listening who might be heading into that, it’s like, first of all, get a full understanding of your metabolic health, hopefully through blood biomarkers, through your doctor or through a lab outside of your doctor, know where you stand, learn strategies to get blood sugar under control, stabilize blood sugar, which we can certainly talk about. I know we talked about a lot in our first episode together. And then really, start building muscle so you go into menopause with a really good armor on, that’s basically a big blood sugar-stabilizing armor. So, that’s one thing that I just hear so much with women. They’re working out five days a week, but they’re not actually building that muscle. And I think you can really think about it as like a shield to buffer some of the effects of the dropping of estrogen in menopause. One of the women who are, one of the experts who really gets into this so deeply is Dr. Gabrielle Lyon, who just came out with a book called Forever Strong, all about the power of muscle. And even something we haven’t realized until recently is that muscle is actually a hormone-secreting organ. So, muscle actually secretes myokines, which are basically pro-metabolic anti-inflammatory hormones. And so that’s just a really powerful tool, resistance training, towards buffering out a lot of this.

Katie: I’m a big fan of her work and her book as well. I think for women, especially, it’s such an important topic along with all the things we’re talking about truly because like you said, these impact all of us, but especially women, we have these other factors to consider, especially at different phases of life and hormones. And I feel like we’ve made such an incredible, you have, an incredible and strong case for the importance of understanding this data and using it in an actionable way. So, I’d love to take a little time to see, I know you have a huge dataset of what are the patterns you’re seeing of impactful changes people can make, especially once they get this data and have access to understanding what’s going on in their bodies. Are there things that seem generally and universally helpful resource diet or lifestyle changes that people can make that can help move things in a positive direction?

Casey: Definitely. So, it’s funny. I just, I was telling you before we started recording, like I just finished my first book, which isn’t coming out for a long time, but I’m sitting here after finishing the book and turning into my publisher, and I’m like, it’s 380 pages, and there’s like thousands of references. And I’m like, what, what is the biggest takeaway from this book about metabolism and blood sugar? And I honestly think one of the biggest takeaways aside from the obvious, which is, like, get the refined sugars and the ultra-processed grains out of the diet, which basically turns straight to glucose in the bloodstream and eat more whole foods, like that one, kind of a given. But the second one is like, walking is probably the most powerful superpower that we have for metabolic health, and we just do not emphasize it enough. And that to me, like it’s just reading all these papers, looking at all this research, looking at all our levels data. We need to be walking so much more as a culture. So now, the average American is walking about 4,000 steps a day, which is about two miles. And when you look at like modern hunter-gatherer tribes, they’re walking like 20,000 steps a day. So, like literally five times more. And what’s interesting is that walking, even though it’s easy and it almost seems like, how could that be so powerful? Basically, the way I think about it is if you’re even walking 10 feet, you’re activating almost every major muscle group in your body. You’re swinging your arms, you’re using your legs, you’re using the big muscles of your legs, and even using them at that really low intensity, it’s causing all these pathways inside those muscle cells to become activated. And so, there’s all these cell signaling pathways that essentially bring glucose channels from the inside of the cell to the cell membrane if the muscle is activated at all. And so, someone who sits for three-hour stretches, which is a lot of us, I mean, like, and doesn’t really get up or ever use that muscle, their glucose channels are just going to be sitting inside the cell inactive, and those cells are not going to be taking up glucose. But if you get up and walk for one minute every hour, you’re bringing those glucose channels to the cell membrane to take up glucose and use it. So, someone who’s moving even for one minute, every 30 minutes, every hour, their body all day is basically bringing those receptors to the membrane to bring glucose out of the bloodstream. Now compare that to someone who sits for like three-, four-hour chunks, maybe gets up to go to the make a lunch, gets up to go to the bathroom every few hours, but otherwise they’re just sitting at their computer. That person, their cells just aren’t getting primed to take up glucose. And so that glucose is going to stay in the bloodstream, it’s going to be more erratic. And let’s say that person even goes and does a workout in the evening after work. So, they’ve sat most all the day, and they work out for 35 minutes for an hour or whatever. That’s great, but it doesn’t change the fact that during that entire rest of the day, inside their cells, their glucose channels were not active. So, we really need to flip the script from this concept of like exercising is the answer to actually regular low-grade movement is a huge part of the answer. Cause it creates a totally different physiology in the body throughout the day.

So, a little like mental image, I want people to really ingrain is that by setting an alarm on your iPhone every 30 minutes to get up and do five air squats or to walk around your apartment or walk around the perimeter of your house or walk once around the block. It’s not just for the sake of getting steps. It’s for the sake of truly giving your body an energetic signal to change the cell signaling pathway, to bring glucose receptors, glucose channels to the cell membrane and keep your body in this constitutively active state of metabolism and glucose uptake. Exercising for an hour at the end of the day is not going to mitigate the effects of sitting all day. And so, yeah, it’s just every time you move those muscles, it’s truly sending a different signal to your body. The research is pretty profound. Like if you, we talk a lot about 10,000 steps, but actually, a lot of the research I looked at for the book, the real magic number appears to be 8,000 steps, and 10,000 is great, and you might get some marginal benefit, but somewhere between the 8,000 to 12,000 steps is basically enough to reduce your risk of heart disease, type 2 diabetes, obesity, stroke, depression by about 50%. So, if you can get a wearable and just confirm that you’re walking at least 8,000 steps a day, it’s basically equivalent to having the most effective medication, like ever invented for any disease in terms of prevention. Like it’s actually much, much more effective. We don’t have any medications that reduce risk that much for those diseases. So, it is close to a silver bullet.

Another concept, I feel like I’ve been grappling with a little bit is that, you know, is the concept really of exercise almost like distracting us from moving more throughout the day? We think that the concept of exercise is this idea that you have this thing on your to-do list, and you have to check it out off every day, and that will make you healthier. And yes, exercise is great. But America spends more on exercise than any other country in the world, and we are among the heaviest and getting sicker. The average American household spends $2,000 a year on health and fitness-related expenses, and that number is going up over time. We have more gyms per capita than any country in the entire world, and we are one of the sickest and heaviest countries in the world. So, there’s some disconnect between the amount we’re spending on fitness, the amount of gyms we have, the amount of “exercise” we’re working towards, and our actual outcomes. And I think that disconnect is the fact that we’ve overemphasized this concept of exercise, and we’ve under-emphasized the concept of just moving your body more regularly.

And when you look at like Dan Buettner’s work in the blue zones, this makes sense. The populations that have the most centenarians, the people who live to 100, are the populations who movement is just built in to their everyday life. Whether it’s farming or walking long distances to get things that they need for just the daily living. And so, this creates a big challenge for us because now, in America, a lot of us are knowledge workers. We work at computers. That’s just the reality. We’re not going to go back and all become farmers, nor should we necessarily. But what it does mean is we do have to get very creative about our day-to-day lives because just because we’re knowledge workers doesn’t mean that we can actually stop moving if we want to stay healthy. This might mean standing desk. This might mean treadmill desk. This might mean setting an alarm every 30 minutes on your phone and doing those five pushups, five air squats, walking around your house or apartment. This might mean having the default for all of your calls be walking meetings. It might mean rescheduling your next few dinner dates or coffee dates to be walking or hiking dates. It’s just having to be really bold and creative to somehow build movement into our day-to-day lives as computer-based knowledge workers because there’s really no way of getting around it. We either move or we get sick. And so that’s a long answer to your question. But we really have to start getting more creative about marrying the modern world that we’re living with, living in with the reality of our biology, which is that low-grade movement throughout the day is absolutely necessary and unavoidable if you want to be optimally healthy. So that’s a movement-focused one.

We already talked about resistance training, which I think is another thing, especially for women. It’s like gotta incorporate it. I have so many conversations with people, with Levels members who say, “I’m stuck, and I’m not getting the results I want, and I’m doing everything right. I’m eating healthy, I’m sleeping, I’m meditating, I’m working out five days a week.” And invariably, I say, “Are you resistance training?” And they say, “No.” So that’s a big one. We got to build the muscle.

And then from the food standpoint, I’d say, one of the biggest practical takeaways that I’ve seen from our Levels data, and, at this point, we have over 500 million glucose data points. We’ve had many tens of thousands of people go through the program and log their food. And one of the biggest things I’ve seen is that breakfast, essentially breakfast, can make or break someone’s day metabolically. So, if there’s one meal you’re going to focus on improving for you and your kids and your family, it’s breakfast. And the reason I say this is because what we see in our dataset is that some of the very best scoring things on our dataset are breakfast, and some of the very worst, like worse than dessert scoring things that we see in our dataset are breakfast. And I would assume that on both ends, people think that they’re making healthy choices. And so, for instance, on the unhealthy end where we see the biggest glucose spikes, it’s things like, it’ll be people eating things like granola or instant oatmeal or a piece of whole grain toast. We know that pastries, like donuts and bagels and muffins, that those are going to be unhealthy, and those are certainly in the high glucose spike category. But some of these more seemingly benign foods like toast or oatmeal or some cereals that might be low-fat or might seem healthy like granola. Some of the biggest spikes we see in our dataset are those.

And so, then you’ve got on the other side, you’ve got some breakfasts that don’t cause virtually any glucose spikes. So, these are things we see like eggs and avocado, eggs and greens, even eggs and bacon, or eggs and ground beef, frittata, chia pudding. We get a lot of people who log what’s called the fab for smoothie, which is the smoothie recipe that Kelly LeVeque, celebrity nutritionist Kelly LeVeque, popularized. She’s one of our advisors. And it’s amazing to see how many people log that smoothie, but basically, it’s like a very well-balanced smoothie of protein, fat, fiber, and greens and very low glycemic. That scores really well. So, I think the takeaway for me is that, essentially like, eliminating those foods that have the refined grains or any processed grains in them, cereals, toast, bagels, obviously pastries, muffins, croissants, things like that. Just those tend to just really, really crush people. Stick with the protein and fat-forward, fiber-forward breakfast. Because when you start your day with a more stable glucose, what we see is that people tend to keep the glucose more stable throughout the rest of the day. And part of this is due to the fact that if you have a big glucose spike first in the morning, often what will happen is that you spike and then you crash. And when you crash, that’s often when people mid-morning feel tired and like they need another cup of coffee and they might feel cravings, they need a little snack, might even feel some anxiety. That’s what happens when you have a glucose crash, and those crashes happen typically after a spike. You don’t have a crash after you have like a low, if you have a low glucose elevation after a meal, you usually won’t crash, it’ll just be more stable. But a big spike usually get a big crash. That crash is called reactive hypoglycemia. And there was a really interesting paper actually in Nature Metabolism last year, like premier medical journal, that showed that the extent of those post-meal crashes, reactive hypoglycemia was predictive of how many carbohydrates people would eat in that entire day and how hungry they would be that day. So basically, you spike yourself and crash yourself, you’re going to be craving more carbs that day, you’re going to probably eat more calories over the following 24-hour periods. So, if you can stabilize your glucose for breakfast, you’re setting yourself up for like a 24 hours of success and less craving. So yeah, just really getting the refined grain breakfasts out of the rotation, I think, is one of the best possible things you can do to start your morning strong, keep your energy stable, and reduce your cravings throughout the rest of the day.

Katie: Those are such awesome tips. I was taking notes as you were speaking, and I know that through Levels, you guys have a specific offer to help people be able to take all that data into account as well. So that will be linked in the show notes for you guys listening on the go, that’s, [email protected].

And I feel like we never have enough time when we get to chat because you’re such a wealth of knowledge, and we could chat all day long. So perhaps we can do another round sometimes as well. But this has been so helpful and so actionable. And I love how deep and specific you got to go on all these different topics that I think really can be impactful for everyone listening. So, Casey, thank you so much for your time. This has been such a joy, and I’m so grateful that you were here.

Casey: Oh, it is totally my pleasure. And as we were chatting, I realized that for some of the biomarkers, I gave optimal ranges, and for some, I didn’t. So, I’ll make sure to send you the list of all the optimal ranges for all the tests that I mentioned. And maybe those can be in the show notes, but like uric acid and whatnot and all those. So, want to make sure people have those, but I’ll follow up with all of those for you.

Katie: That sounds perfect. And I’ll make sure as well as links too. I know you guys have a tremendous amount of educational material on all of this for people to keep learning and that you release a lot of content around it as well. So, all of those links will be in the show notes, but I am deeply grateful for your time. Thank you so much for being here today.

Casey: Thanks, Katie.

Katie: And thanks as always to you for listening and sharing your most valuable resources, your time, your energy, and your attention with us today. We’re both so grateful that you did, and I hope that you will join me again on the next episode of the The Wellness Mama Podcast.

If you’re enjoying these interviews, would you please take two minutes to leave a rating or review on iTunes for me? Doing this helps more people to find the podcast, which means even more moms and families could benefit from the information. I really appreciate your time, and thanks as always for listening.

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