Good Life Project - What if We’ve Been Missing One of the Biggest Causes of Disease? | Benjamin Bikman

Episode Date: May 29, 2025

Unlock the secrets to reversing insulin resistance - the hidden driver of many chronic diseases like heart disease, cancer, and Alzheimer's.In this eye-opening episode, Dr. Benjamin Bikman, biomedical scientist and author of Why We Get Sick, reveals surprising truths about carbs, fats, protein, stress, and lack of sleep that can help you reclaim your metabolic health and resilience. Don't miss these game-changing strategies from a leading expert in the field.You can find Ben at: Website | Instagram | Episode TranscriptIf you LOVED this episode, you’ll also love the conversations we had with Dr. Gabrielle Lyon about maintaining and building muscle through nutrition and exercise.Check out our offerings & partners: Join My New Writing Project: Awake at the WheelVisit Our Sponsor Page For Great Resources & Discount Codes Hosted on Acast. See acast.com/privacy for more information.

So, have you ever felt just completely blindsided by some health issue that seemed to come out of nowhere? Like one day everything's fine, the next year is slapped with a diagnosis that turns the world upside down, or just symptoms that you can't figure out? Well, get ready because what you're about to hear may just rewrite everything you thought you knew about health, disease, and how to achieve true metabolic fitness. My guest has uncovered a common denominator that links many of the most prevalent

chronic diseases of our time, from heart disease and cancer to Alzheimer's and infertility. It's not just what you eat, but something much deeper that's been hiding in plain sight. Dr. Benjamin Bickman is a brilliant biomedical scientist, and he's here to kind of blow the lid off one of the biggest missed opportunities in modern medicine, something that he calls insulin resistance. Ben earned his PhD

in bioenergetics and did postdoctoral work at Duke National University of Singapore specializing in metabolic disorders. He's the author of the groundbreaking book, Why We Get Sick, and a professor laser-focused on cracking the code of insulin's effects when it goes awry. And during our conversation, he reveals some really surprising truths about things like carbs, fat, protein, and how getting the balance right is critical for insulin sensitivity. You'll also discover the overlooked roles of stress, inflammation, and even lack of sleep in fueling this modern epidemic that often goes completely unchecked. And he shares powerful, pragmatic strategies to first help identify when insulin resistance

is present, and then what to do about it. So if you've ever struggled with a chronic condition, been frustrated by conventional advice, or simply want to optimize your metabolic resilience, get ready. This conversation just might change everything for you. So excited to share it with you. I'm Jonathan Fields, and this is Good Life Project. When I think about the work that you've been doing, I feel like variations of metabolic syndrome, metabolic dysfunction, glucose intolerance, pre-diabetes, these have been part of the

conversation, the sort of like the health and well-being zeitgeist for a while now. Your focus is in an area that is related but different and something, it's a topic I really haven't heard explored in a meaningful way and I'm excited to dive in. And that topic is really, it's the idea of insulin resistance. So let's start out with sort of like a defining question here. When we're talking about insulin resistance, what are we actually talking about?

Yeah, and in fact, just to give a bit more of a preamble to the answer, what I think is important, an important context with this conversation is you'd mentioned at sort of the warm up to the question talking about metabolic health, even that term requires definition. It sounds nice and yet it's a little vague that it's really open to interpretation. I strongly submit that when we say metabolic health, whether we know it or not, we're actually talking about insulin resistance, simply because most often metabolic health in a technical way is defined by the metabolic syndrome. And the metabolic syndrome is the insulin resistance syndrome. That's what

it used to be called. So the insulin resistance problem of this, really two parts, two things that always come together, the swirling yin and the yang of metabolism here, is this two-part problem. Namely, that the humble hormone insulin is altered in its ability to influence cells. That when insulin comes and knocks on the door of a cell to tell the cell to do something, that something is getting a little lost in translation, that there is some disruption, that the signal isn't being carried throughout the cell with the optimal fidelity that we would expect in a healthy situation. So that's the one part of the problem, which is, again, that the hormone insulin isn't

working entirely well. But at the same time, mingling with this problem is the situation of chronically elevated insulin. And that is a part of the understanding of insulin resistance that most people don't think. They only think of what the term evokes, namely this idea that the hormone insulin isn't working particularly well. In order to appreciate how insulin resistance really hurts the body, you cannot leave that other part out of the description, which is that insulin is higher than normal. And just to help people appreciate why this even matters, most often people hear the word insulin and they think that it's only relevant to a conversation about a diabetic. And yet, insulin

affects every single cell of the body, without exception. Every single cell of the body responds to the hormone insulin to varying degrees. And because so many, all the different cells of the body do different things, it's no surprise to learn that insulin can have different effects at different cells. But the thematic effect, if we were to put an umbrella over top of all of this, that umbrella would be metabolism. That insulin influences, indeed, directs the cell on how to use fuel, what to do with calories, what to store, what to burn, what to convert. All of this is going to be heavily, heavily influenced by insulin, regardless of the cell type.

So if we start from that premise, and what I want to understand is the scrolling thought in somebody who's joining us so far is probably going to be okay, so I understand that it matters, but why does it really matter to me? What does this do? What does insulin resistance actually doing to us? So maybe we can start with more of like a broad picture. Yeah. Why we actually want to go deeper into this.

Like what are the potential negative effects that this is having when we have insulin resistance? Yeah. Yeah. Well, the answer is so consequential that I considered it sufficiently valuable to devote my career to. You could almost lay up all of the chronic diseases on a wall and then just start throwing the dart. Whichever one the dart hits, there's going to be a clear mechanism that explains how insulin resistance either directly caused the problem or exacerbated the problem. Like,

for example, heart disease, the leading cause of death for now unless cancer overtakes it and it's on pace to overtake it. So what is the connection between insulin resistance and heart disease? Well, multiple, but the most obvious one is the effect of insulin resistance on the blood vessels. So one of the leading risk factors for heart disease is hypertension. The most common cause of hypertension is insulin resistance. So the average individual who's listening to this and they've been told they have hypertension and they're on one or two blood pressure medications, I can almost guarantee, it is almost certain that the main driver of their hypertension is insulin resistance. That when insulin is chronically elevated, again back to that two-part definition of insulin resistance,

that elevated insulin is forcing the kidneys to retain water. And where you're retaining more water, you have a higher blood volume, where you have a higher blood volume, you have a higher pressure. At the same time, the blood vessels are becoming insulin resistant. And insulin normally has a vasodilatory effect. But when the blood vessels become insulin resistant, those endothelial cells are no longer signaling the dilation, when the blood vessels become insulin resistant, those endothelial cells are no longer signaling the dilation and the blood vessel thus stays constricted, which further increases blood pressure. So that's just one aspect of how insulin resistance touches on heart disease, the main cause

of death. But with cancers, the two most common cancers in men and women is prostate cancer and breast cancer respectively. Both of them are tightly linked to insulin resistance where – with breast tumors this is the case where every tumor that is sampled has a dramatic increase in the number of insulin receptors. An insulin signals growth. That's part of its metabolic signaling. It's an interesting adaptation or mutation that the cancer cell has undergone in order to grow faster and better, if you will. It becomes more and more sensitive to insulin and at the same time, we make matters even worse because while insulin is stimulating growth, all that glucose that the person's eating is fueling that growth because cancer cells prefer glucose as a fuel. And so with heart disease and cancer,

the leading causes of death, we have direct connection of insulin resistance. And then maybe just to round it all out, even Alzheimer's disease is increasingly considered insulin resistance of the brain. My lab has published multiple papers on this and others have too, documenting some of the bioenergetics that are shifted in cognitive decline, where to one degree or another, the brain is starting to go hungry because it can't meet its metabolic demands

by relying on glucose because of its insulin resistance. The insulin resistant cells aren't able to pull the glucose in as well. So it may be surrounded by glucose in the blood and yet the brain can't get enough and so it starts to go hungry and with this energy deficit comes a deficit of cognition and then we have this cognitive decline which is the hallmark of Alzheimer's disease. So from top to bottom, we could continue to go through the bone pathologies, muscle pathologies, joint pathologies, liver problems, and infertility. And the common theme among all of them would be a metabolic

origin, namely insulin resistance. I mean, it's incredibly powerful how you describe the linkage to nearly every system, every organ, every part of our body, and also its potential to go off the rails, you know, to head into dysfunction and eventually disease. We hear often that one of the common things that we see across all sorts of degenerative conditions, inflammatory conditions, is actually inflammation. Is there a relationship here between insulin resistance and more broadly inflammation in the body? Oh yeah, absolutely. In fact, I'm thrilled to talk about this because that was the focus

of my entire postdoctoral work many, many years ago when I did a fellowship with Duke Medical School, actually as just a point of interest. It was at a collaborative medical school found in the beautiful island nation of Singapore. So I moved my devoted wife and our small little family to Singapore for a few years and it was an incredible experience. But the whole purpose of this was to identify the biochemical pathway that explained how elevated inflammation and elevated levels of what's called inflammatory cytokines. And anytime anyone hears the word cytokine, just think of a hormone that's involved in inflammation,

either promoting it or inhibiting it. Cytokines is going to be a term that encompasses all of those things. We had seen and others have too, that when these inflammatory pathways are turned on, it causes a rapid onset insulin resistance. So inflammation falls into a category. When I talk about the origins of insulin resistance, I talk about fast insulin resistance and slow insulin resistance. Inflammation is fast insulin resistance. Literally within hours, if we were to take an individual, and this has been done in humans, and increase their inflammation by injecting some sort of inflammatory activator, you can document almost a real-time change in their insulin resistance. And so the biochemistry of it's fascinating, but to make a long story short, or multiple publications into a distinct answer here.

When a cell has its inflammatory or immune pathways turned on, one of the responses will be an accumulation of a type of fat called a sphingolipid named ceramides. Just to be very, very precise for anyone who's interested in this. So more inflammation leads to an accumulation of ceramides within the cell and then ceramides are a direct antagonist or a direct disruptor of the insulin signal. When insulin comes and knocks and the cell wants to respond with a series of events, ceramides basically are like a stick in the spokes of the bicycle stopping it in its tracks. I mean that makes so much sense in that it would be just essentially tied to inflammation,

which then I guess also you could make the argument that if you have that relationship, then anything related to inflammation in the body is also going to be related to this. And then you start to extend out, I would imagine, to chronic pain, to osteoarthritis, to all these other conditions that are in some way linked to inflammation. Is that right? Yeah, yeah, for sure. Anything that increases inflammation will increase insulin resistance. And even with autoimmune disease, as you'd mentioned, osteoarthritis, that makes me remember a paper that was published that documented the movement, the ebb and the flow of rheumatoid

arthritis, where they documented in this study. And rheumatoid arthritis is one of the more common autoimmune problems. And like most autoimmune problems, it will ebb and flow. It will have a time where the disease subsides a bit and then it flares up. Well, you can track the insulin resistance right along with it. No other changes in their habits, but when the disease is active,

they are insulin resistant, or more than they would have been earlier. When the disease is active, they are insulin resistant, or more than they would have been earlier. When the disease quiets down, so too does the insulin resistance. You mentioned in the context of the brain, Alzheimer's. What about on a more pervasive and often a much younger basis, mental health challenges, depression, anxiety? Do you see relationship between insulin resistance and those things that are so pervasive across so many people of literally like all

ages? Yeah, I mean, there's no questioning the fact that we are living in the midst of among all the crises we have, and it's almost too many superlatives, it seems nowadays, but mental health is really suffering. And it behooves us to wonder at the role of metabolism in this. And yeah, what's interesting about neurological complications like Alzheimer's disease is that there is once again, a common thread that's weaving through all of these. So we have, I elaborated a moment ago how with Alzheimer's disease, there is this, an insulin resistance that results in the brain not

getting enough glucose to fuel its metabolic demands. This is a phenomenon that is referred to as brain glucose hypometabolism. So a brain that is not burning glucose to match other healthy brains. And you see that with Alzheimer's disease like I've documented. Now importantly, you can see that as young as people in their 20s. you can start to detect these differences in brain glucose metabolism. So that could be the earliest sign of future cognitive concerns. But as you noted, what about other brain related things like depression? Well, you can look at Alzheimer's disease in that brain glucose hypometabolism is a common thread as I mentioned weaving through migraine headaches and epilepsy and yes even depression. So even in cases of major depression,

you can detect a brain glucose hypometabolism and then it's no surprise not to hijack the conversation and go into a direction we don't want to. But suffice it to say, if all of these are manifestations of a brain that's a little hungry because it can't get enough fuel from glucose, all the more reason to explore therapies that allow the brain to fill that energetic gap. And there is one nutrient that is capable of filling that gap, although it is heavily vilified and still is to a large degree, but that is ketones. Ketones are the preferred fuel for the brain. It's a strange thing that we have a culture that is obsessed on stating that the brain must have this 100 and whatever grams of glucose and thus you have to eat that much glucose. That's wrong on multiple

levels but at least one level of error is that it suggests that the brain prefers glucose, and that is demonstrably untrue. By that, I mean you can prove it false and it has been proven false. The brain prefers ketones, and this is evidenced in human studies where you put in – the humans have an equal amount of glucose and ketones in the blood, and the brain is using way more ketones than it is glucose. Even if it has equal access, thus its preference becomes clear. It's ketones. And then to bring it back to the question at hand with regards to say mental health disorders, there are increasing number of peer-reviewed studies

that document and indicate clearly that when the brain is given a chance to metabolize ketones, these mental health disorders improve. Whether it is depression, whether it is bipolar disorders, whether it is even eating disorders, in every instance there are clinical studies and case studies that have been shown to, that indicate that ketones are therapeutic and it is likely a result of simply actually fueling the brain. I wanna put a pin on the conversation around ketones and circle back to it a little bit later in conversation

because I think it is really important, but let's drop back into it when we shift a little bit more into some of the what can we do modes. I do want to use that a little bit more just understanding the nature of the problem as well. So you sort of describe what insulin resistance is, how it affects all the different systems in the body. There has been so much focus, I feel like recently, on glucose. And this is clearly related. There's

a relationship between insulin and glucose in the way that we fuel our bodies and our cells. We hear phrases like glucose intolerance, pre-diabetes, type 2 diabetes. Increasingly, people are wearing the portable monitors, a continuous glucose monitor to try and measure their glucose to see if they can make that better. Tease out the distinction here between insulin resistance and things like glucose intolerance, pre-diabetes, and why we shouldn't just be paying attention to glucose, but also insulin levels. Yeah, well, that's a great setup for me,

the way you just framed it at the end. To be really clear, without a doubt, there is an intricate connection between glucose and insulin, but there's also a critical distinction that needs to be noted because in the absence of teasing the two apart or appreciating the meat just separate entities, it leads us down roads where we're detecting problems too late and we're treating them very, very incorrectly. So to be really clear, the primary stimulus of insulin is blood glucose and that's important because as much as we were earlier

describing how discussing how inflammation is a cause of insulin resistance and it is the most common cause of insulin resistance is chronically elevated insulin. So when a person is living a life where they're constantly spiking their insulin, over time those spikes start to merge together and the person isn't able to bring the insulin down very well before it's spiked back up. And that's largely a result of our chronic carbohydrate consumption. And we do globally consume carbohydrates at an obsessive level. 70% of all calories consumed globally are carbohydrates. And

we've been giving the remarkably, I want to try to be diplomatic, the interesting advice to eat six times a day, which is a way to ensure that insulin is elevated every waking moment. So again, the primary driver of elevating insulin is blood glucose. And one of insulin's most famous jobs, arguably it is its most famous job, although not its only job. I'm not saying it is its only job or its even most important job. Insulin's most famous job is to lower the glucose in the blood by knocking on the doors of certain cells like muscle cells and fat cells and then having those cells open up doors to allow the glucose to come in,

thereby correcting the blood glucose and now insulin having done one of its most relevant jobs, insulin now comes back down as well. So this is the connection between the two, but they're not the same. So you'd mentioned pre-diabetes and type 2 diabetes and that's a really helpful example for me to illustrate this, that when a person is in the pre-diabetes stage, that is synonymous with insulin resistance. So when you hear pre-diabetes, think insulin resistance. But that is a state where the insulin is higher because it's insulin resistance, but the insulin is with this higher amount working well enough to keep the glucose normal.

That is such an important perspective because with this perspective in mind, we can appreciate that if we are only looking at snapshots of fasting glucose levels once a year on an annual wellness visit, we will not be detecting the metabolic problem. That this glucose-centric paradigm has us missing the diagnosis. Because if we were actually measuring insulin, we would say, hey, your insulin is at 30 micro units per mil. That's way higher than it ought to be. I wonder if that's what's driving your hypertension and your tinnitus and your migraine headaches and your infertility, because all of those are related to the insulin resistance state, not necessarily a hyperglycemic state. So this is insulin resistance, elevated insulin,

but working well enough to keep the glucose at a normal level. And because of our glucose-centric view of metabolic health, we don't detect the problem. And this is a state that can last for 10 or 20 years. It can be decades until the glucose finally starts to climb. That's why I say this perspective is so tragic because we don't detect the problem accurately. We don't diagnose the problem as being metabolic. And then it's only once the glucose finally starts to climb that we now say, oh, and you also have a metabolic problem so here's a drug to try to control your glucose, as we've now diagnosed you with type 2 diabetes, which is now high insulin and high glucose. But

again, the glucose is not the main character of the story. What's driving all of these pathologies isn't the high glucose, although it can cause some on its own, but the primary driver of these diseases of civilization or these plagues of prosperity is the elevated insulin and the insulin resistance that it represents. But then one final point on this, not only does the glucocentric paradigm have us detecting the problem too late, but the glucocentric paradigm also results in us treating this problem very, very wrongly because if you take a person who's in type 2 diabetes,

you are only looking at the glucose. The low-hanging fruit is for the clinician to say, I'm just gonna push your glucose down by pushing your insulin up even higher. And so I'm gonna give you an insulin-secreting drug, like a class of drug called sulfonylureas, meet that qualification, or I'm just gonna give you insulin. You're gonna be on an insulin therapy.

And this is already a hyperinsulinemic state. And now we're pushing the insulin even higher because we have no appreciation of the fact that it is the primary disease driver. And so ironically, although it makes all the sense now, I hope, given how I've explained it, in the midst of controlling the type 2 diabetics glucose more and more aggressively, with insulin, the more we're

relying on insulin, the more we make them fat and kill them. They gain weight. They're three times more likely to die from heart disease and they're twice as likely to die from cancer and two times more likely to develop Alzheimer's disease. The more aggressively we're giving them insulin, even while we're getting their glucose in a manageable or a good range, because these are not glucose problems, they're insulin problems. And so the more we are pushing insulin up to try to help the type 2 diabetic, the more akin this situation is to giving an alcoholic another glass of wine, hoping that the alcohol is going to cure the problem So here's my question in response to that every annual I've had you know, like is a fully formed adult

Especially like later in my life. We're always testing the markers for glucose. Like what are my glucose levels? What are my fasting glucose levels? What's my a1c? I don't know if I've ever actually had a test to measure my insulin level. So if this is knowledge where there's strong research behind everything that you're saying, and I don't doubt that there is, why are we still sort of like following this paradigm and testing the way that we're testing and not testing the way that we're testing? Yeah, yeah. I think there are probably three, off the top of my head, I think I can articulate three reasons for this glucocentric paradigm and why it's persisted. Let me elaborate

them and speak them out loud to help me remember them in real time. So one would be probably historical and scientific and then drug. With history, we were only able to measure insulin within this last generation. That measuring hormones is a much, much harder thing to do than measuring nutrients in the blood. Like measuring glucose, lactate, ketones, all of those in fact are so easy to measure that all of them have been micronized to a point that you can slap a little device on your body

and measure them continuously. All of them. You cannot do that with any hormone, let alone insulin, and we're years away from being able to do that. So there's that scientific hurdle. Historically, I should have said that the most common symptom of the diabetes in a person was the glucose-related symptom, namely the excess production of urine. Because when blood glucose levels get really, really, really high, the kidneys are trying to dump all of this glucose out, so the person is urinating a lot. That's actually what diabetes

means. Diabetes means the excessive production of fluid or urine. So we have that historical and scientific perspective, which is all I think we could all kind of agree to that. The last one is maybe a little more cynical and perhaps a little more controversial, but it's that glucose is a druggable target. In like the ways I just mentioned, there are drugs, there are injections and pills you can pop that will lower glucose, but there are not drugs that really effectively lower insulin. And so it's a cynical view, but I don't think it's wrong, that I think a lot of our modern medicine has focused on markers but I don't think it's wrong, that I think a lot of our modern medicine has focused on markers that actually don't matter

as much as others, but we focus on them because we can give a drug. And now there is some cynicism underlying this answer, and I want people to kind of find the cynicism in how I'm explaining this, but I don't think that means it's not right. That the more the kind of weaving of pharmaceutical interest with modern medicine, I think its influence is at least partly shown in this example.

Why focus on glucose when insulin matters more? Because you can drug glucose better than you can insulin. Why focus on LDL cholesterol when triglycerides matter more and are more predictive of heart disease. It's because there's not a drug that addresses triglycerides, but there are lots of drugs that address LDL cholesterol. So I can't help but think that has influenced some of our clinical paradigm. I would offer also, I'm curious what your take is on this in addition to those three things or like even relevant to the last one, I think just we as individuals need to raise

our hands and take some responsibility for certainly the behavior that we exhibit too. We're a culture that I think tends to look for what is the quick fix? What is the short term? What is the thing that I can take to solve the problem? If I can pop a pill or do something really simple once a day and in theory that quote fixes things, I think most of us would be like, oh, I'd rather do that than make a lot of behavior change, a lot of lifestyle change, a lot of nutritional change. And look, understandably, this is a huge amount of effort that we're

potentially asking people to do. And we'll get into some of this shortly. So I think there are reasons that get spread all around and some of it just rooted fundamentally in the human condition and human behavior and why we go for things that are just fast and easy. Yeah, path of least resistance. Yeah, always. And look, I'm raising my hand there too. I'm human too.

And we'll be right back after a word from our sponsors. You mentioned that one of the causes of this is lifestyle. Actually, before we even get there, I want to kind of close the loop on what we were just talking about. What should we be testing? If we commonly get the glucose-related tests, when you go see a doctor, what should we be testing and also what should we be looking for ourselves to trigger us to think that maybe we actually need to get the appropriate testing? Yeah, yeah, that's a great question. I'm glad you brought that up. Nothing delights me more

than sharing some actionable insight in this would be some of it. So one way to determine someone listening to determine your, where you are on the spectrum of insulin resistance to insulin sensitivity would be to look at your own health as you know it now. For example, where you are on the spectrum of insulin resistance to insulin sensitivity would be to look at your own health as you know it now. For example, have you been told you have high blood pressure? That really is extraordinarily solid evidence that you have insulin resistance. Similarly, do you have a first degree relative like a parent who was diagnosed with type 2 diabetes or did your mom have gestational diabetes, which is sort of a mini version of type 2 diabetes induced by pregnancy, then if yes, then you very likely have insulin resistance. Also, the skin. The skin is a window to the metabolic soul where you need

to look no further than the neckline, the collar line. And if around your neck, especially around the back, if you have a line of darker crinkled skin, that's a condition called acanthosis nigricans, and it's extraordinarily good evidence of insulin resistance. Coincidentally, at that same location, either around the neck or anywhere where you have a skin fold, like maybe the armpits, for example, if you have teeny little mushrooms of skin, those are things called skin tags. I think people probably know what I'm talking about. You've seen them. These small, not like a big rounded hill of skin, but a teeny little mushroom stalk. Those are skin tags, and they are also extraordinarily solid evidence of insulin resistance. So those are some things

that you could probably determine relatively easily, but if you are able to get a blood test or you've had one recently, first and foremost, do whatever you can to convince your clinician to measure your fasting insulin. If that fasted insulin number is six micro units per mil and less, that's a great sign that you're insulin sensitive. Low insulin suggests insulin sensitivity. And then if it's up to the mid teens or so, that may be a problem. You might have caught it at a high point, like every hormone, insulin has a bit of a rhythm to it. But if it's up into the high teens and into the 20s, that's an absolute red light or red alert. You are probably insulin resistant. Now,

let's say you don't have a clinician who's open-minded to measuring insulin, and some aren't, unfortunately, then there is a measurement you can use as a surrogate, and that is the triglycerides divided by HDL cholesterol. That is the triglyceride to HDL ratio, and it shifts a little bit across the various ethnicities, but the general average is around 1.5 as you look across ethnicities. Some have a cutoff that's closer to one, some have a cutoff that's closer to two, but the triglyceride to HDL ratio average range being around 1.5, if your triglyceride to HDL ratio is less than 1.5, that's a great sign. If it's higher than 1.5, that's a great sign. If it's higher than 1.5, it's a warning sign.

Super helpful. It gives us stuff to just kind of look at in our daily lives and also then go ask and see if we can get tested for this. Let's switch gears a little bit and talk about some of the interventions. What can we actually do if we either get results that say that we actually are insulin resistant or we sense we are, we have any of the wide range of conditions or experiences that you have described that may in fact be signals of this, one of the core focuses for you when it comes to how do we actually deal with this is nutrition. I want to break this down, I guess probably an easy way to do it was almost go by macros. Starting out with carbs, because this seems earlier

in our conversation to have been something that you identified as saying, well, this, our approach to carbs, what we've been taught about the role of carbs and the volume of carbs that we need to be eating every day may in fact be a central contributor and maybe reversing that advice may be a big part of the solution.

Yeah, absolutely right. It is extremely appropriate and even necessary to focus on macronutrients. If the solution is to manage macronutrients, the food we eat, when we eat it, how often we eat it is either the culprit or the cure. And that's where the opportunity is. The greatest movement in improving insulin resistance and thus improving metabolic health is going to be by managing macros. And you've started with the one I always start with,

which is number one, control carbs. There are various levels to this definition, depending on where the person is and what their outcomes are, where they're at with regards to insulin resistance, I mean. But at the simplest level, it would be don't eat your carbohydrates that come from bags and boxes with barcodes. And focus on whole fruits and vegetables. Eat them, don't drink them. That's it. And so it would be liberal, liberally enjoy fruits and vegetables for the average individual. And you're going to see

substantial health improvements. And again, those refined sugars and starches, you got to keep those to a minimum. Now, there are two other macronutrients, protein and fats. There are principles with those too, because it's not just an ideology of deprivation of just don't eat these carbs. You can make up for it.

Yeah. So I want to get into them, but before we do that, I do want to go a little bit further into the exploration of carbohydrates. Liberally eat fruits and vegetables and avoid things with labels and boxes, processed foods basically. When you think about, let's break it down a little bit, I think a lot of us look at vegetables and say, okay, so generally a ton of fiber in there, green leafy stuff, all sorts of phytonutrients, really good stuff for us. And generally, especially at least with the quote, less starchy category of veggies, like

relatively low in carbohydrates, glycemic index and things like that. But then we get into things like potatoes on the veggie side. Then we get into fruits, which would seem to be sort of like sugar bombs, but natural. How do we think about the more starch-rich veggies and also the fruits that seem to be just nature's version of glucose injections? Yeah, yeah, yeah. Well, in fact, what's funny is I wouldn't call it nature's version. I'd say what we've done to nature. Yeah, that's a good point, actually. Where the apple, you know, just as a point of interest, easily, easily twice the size, if not more. I mean, just for fun, anyone listening, just go look up, you can see the evolution of the

apple with some human influence. And I don't fault the, I don't fault us as a species for doing this. It's part of our, our genius that we can do these kinds of things, which is to take a plant that has in its native state generations ago was extremely low on its ability to feed a human. In our wisdom, we have in our genius, we have bred them in a way and tweaked them in a way to get them bigger and juicier with more and more calories, all of which are going to be coming in the form of glucose once it hits our bloodstream. So that's the next level down.

So Jonathan, what you're alluding to is sort of where I take it if someone says – and even depending on where they're at, we go one step further. So while my first level was, hey, whole fruits and vegetables, enjoy them. But if I'm talking to an overweight type 2 diabetic, then I go to the level you just took us to, which is the starchy vegetables, like those that grow underground, be very careful with. They're much more concentrated in their starchy content, which will then become blood glucose the moment it hits your gut and then moves into the blood.

Similarly, there are the more sugary of the fruits like the tropical fruits like mangoes and pineapples, they are really going to elicit a substantial increase in blood sugar. Unlike other things like say berries, which interestingly we haven't quite played around with as much as some of the others. And again, I don't mean to sound like I'm some kind of like person who's anti-technology and stuff, not at all. But to me, that is that next level. And so I don't start with it when I talk about control carbs. But I think it's certainly appropriate. So maybe one way of defining it, and allowing me to adhere to my affection for alliteration, it would be focused on fiber, that if the fruit or vegetable is going to have

relatively higher fiber to start sugar content, that's going to be a good one to focus on. You want to try to balance that out. That does actually work pretty well across these fruits and vegetables as we've defined them even further. Then one last trick or hack is to look at your plate, and assuming you're eating all three macronutrients, carbohydrates, proteins, fats, pace yourself in such a way that the carbs come at the end. There was a human paper published a number of years ago that had two groups eating all of the exact same things but in a different order. Carbs coming first or carbs coming last. And if carbs came last, the actual excursion of glucose was almost, it was like 47% lower. Just by having carbs come at the end, just all of the changes in digestion, including likely things like GLP-1 and its effects resulted in a significant reduction in glucose, then

maybe one final comment that I would add would be, in so far as a person's schedule allows, go on a 10-minute walk. Even just 10 minutes is enough to have a roughly comparable, rather similar effect at lowering the blood glucose spike, bringing it down by about half. Again, just something like a modest 10-minute walk. I wanna bring up two other things

before we leave carbs behind. The thing is that I think they make our heads spin a little bit and we're trying to figure out what's real and what's not. What is this concept of net carbs? Now I get that this plays more in the domain of processed foods, whether it's a bar or something that comes in a box or package. Often you'll see, if you look on the nutrition label, you'll see 20 carbs, but then there's three net carbs.

How do we understand this? I do think it's real just because I look at these carbohydrates as I see them through the lens of how much are you going to affect my blood glucose. And just by way of required claims isn't the right word but accounting of calories and macronutrients on a food label, some things like soluble fiber which is not capable of being converted into blood glucose still has to be counted as a carbohydrate because it falls into that family. Something like the rare sugar allulose which doesn't at all have the same effect of anything. It has an anti-blood glucose effect, and yet it has to be counted as a carbohydrate on a food label. So I do think it is important

for the manufacturer to be able to have that, to leverage that kind of nuance and highlight the fact that, look, I have to count this as a carb legally, and yet it's not going to affect your blood glucose. So I'm taking it out of the total carb content or count. And then what you're left with is the amount of carbs, the grams that can actually directly have an effect at increasing your blood glucose. So I can appreciate the fervor with which some people rail against it.

I also appreciate its utility and I do think it's justified. Yeah. So you brought a value list, which brings me to the last thing I want to touch on before we leave carbs behind, which is the idea of artificial sweeteners. I have heard from different researchers,

different people, experts in the field, different things about how to think about artificial sweeteners in the context of how it affects blood glucose and then in turn, of course, insulin. What's your take? Yeah, in fact, this is such an important topic at the risk of sounding like a shill here. Right here, why we get sick, I actually put together a specific table knowing that this

is such a topic of interest to just explicitly outline what's the sweetener, what is its effect on its own, and what is its effect when consumed with other carbohydrates because that's an important distinction. And indeed how many people consume it. Like for example, a person who's sipping on a diet soda, that's not the same as sipping on that diet soda when you're also eating a box of French fries or a pack of French fries. So it's an important thing to distinguish.

But keeping it simple, there are artificial sweeteners, there are natural sweeteners, and then there's the rare sugar. Allulose is the rare sugar. It does occur in nature and it is called a sugar even though it doesn't have that same kind of caloric value that sugar does like we think of. And then there are the natural sweeteners like stevia and monk fruit extract. And then there are the artificial sweeteners like aspartame and then like the sugar alcohols like xylitol or erythritol. The simplest way to look at this is by and large, they have no effect on insulin.

That is most certainly the effect with allulose. We are actually in the midst of a human study right now, measuring, looking at allulose and as a control we're using stevia. Neither of those has any effect. Aspartame has no effect as an artificial sweetener, but some of the alcohol sugars like mannitol has an insulin effect. Xylitol may have a little one, erythritol does not appear to have one. So they're not all the same, but by and large, their effect on glucose and thus insulin

is going to be substantially less than that same amount of sweetness if it were coming from like sugar. So unfortunately, there is no definitive answer because there's just such a variety. But just to place a necessary, what I consider defense for some of them, allulose, no effect. Aspartame, no effect. Stevia, no effect. Monk fruit extract, no effect. Now, having said that, some things like stevia are so sweet that the actual amount of stevia you'd get in like a little pack, if you wanted to sweeten your coffee or your tea, the actual amount of stevia is so low that it would be difficult to get it out of the pack that you feel like there's nothing there. So one of the quirks of how manufacturers help you get the stevia is that they'll

actually have what's called a carrier, like a literal flow agent to help the stevia move out of the little pack more easily and all of that is pure glucose. It's dextrose. It's just powdered glucose. So very often if someone's taking what they think is stevia, and they see their blood sugar moving, that's not the stevia.

That's all the extra stuff that's coming out as you're pouring that out, which is pure glucose. Right, so interesting, which also probably just gives you the feeling of like, oh, there's actually something in my packet here. Yeah, because it would be like one or two little crystals of stevia that you couldn't even see and you'd think well I got nothing but just stevia is like a hundred times

sweeter than fructose and so you just need so little of it. So it's just like a little marketing tied in with some functionality there. That's why depending on the sweetener I actually recommend trying to find liquid versions of it. Now with aldolose that's not a problem. It doesn't that that it can be crystallized and used like normal sugar, but like something like stevia, which I am an advocate of as a sweetener, I think in those instances the liquid version is going to be better. Oh, that's so interesting. And we'll be right back after a word from our sponsors. Let's move on to fat. Here we're talking about a macronutrient that so many of us have

had drummed into us, like this is a bad thing. Maybe there's a little bit of it that's good. We all know the olive oil is supposed to be good and there's some healthy fats, avocado is supposed to be good. But there's so much mythology here that you speak to and probably a lot of dysfunction around the way that we have learned to think about fats. Tell me the healthy story around fats and why they're really important in the context of insulin resistance. Yeah. So my rule with fat as part of the whole kind of managing macros is don't fear fat. That we have absolutely a fat phobic culture because of evidence that was put together

in the 1950s, just to give an interesting little history lesson. And here I'm relying on the work of people like Nina Tikols and Gary Taubes, who've kind of been more historical reporters in this regard. But what we know from the 1950s was that a group of scientists created or published what was called the seven country study, where they looked at the degree to which a person's eating saturated fat in a country or the degree to which a country is eating saturated fat and then charted the number of people dying from heart disease. And it was an extremely tight correlation. These seven countries were just tight. Now correlation does not establish causation. We always need to remember that. And I implore everyone who's listening to the sound of my voice, every time you see a headline that says,

meat causes cancer, meat causes diabetes, it's always correlational evidence, and it's always deeply flawed for a reason I'll get into in just a second. But in this seven country study, the scientific group actually left off about 15 other countries that they had data on, but it didn't fit the story. So it was absolute fraud from its very origins.

And that fraud, unfortunately, took on a life of its own, which then gave rise to the dietary guidelines for Americans in the 1970s and then the rest is history. What's funny for me is even at a 30,000 foot view, people who want to say saturated fat causes cancer, red meat causes diabetes, look at our consumption of red meat over the past 120 years and it's been going, it went down. From beginning to now, we eat less than we did before and over the same time span, these two diseases have been skyrocketing among all the others. So even at a superficial level, this doesn't quite make sense. But with the idea of the saturated fat being the problem, it became a machine whose momentum

could not really be stopped. And it continued to feed our fat phobic culture. And what started as a way to try to address heart disease, namely vilifying saturated fat, quickly became part of the anti-obesity story as well. And then that morphed into this focus on calories. And as we continue to have a calorie-based view of fat cells growing and shrinking, fat has more calories than glucose does, than carbs do. That's what led to the whole low-fat movement. While we vilified fat and we embraced all these refined starches and sugars, that was the perfectly wrong thing to do.

So one important thing about fat were two important things. One, it's essential. There are such things as essential fats that a human must eat or they develop nutritional deficiencies and ultimately develop diseases and die. And number two, relevant to a big part of the conversation already, is that dietary fat has no effect on insulin. You can drink olive oil, you can eat a spoonful of coconut oil, you can eat a chomp on a stick of butter, and there's going to be... insulin is an absolute flat line. It does not move. That's important because if so much of what drives insulin resistance

is these chronic spikes in insulin, then if there are calories that we can consume that do not have an insulin effect, that suggests it's a calorie that we should embrace. And at least in my instance, don't fear it. I'm a great defender of fat. And just to put a fine point on it, I'm a defender of ancestral fats. Fats that come from animals and fats that come from fruits are fats that we should enjoy and do so liberally. The fruit fats are like ones we've mentioned, coconuts and olives, for example. Our ancestors needed to only get the fruit and crush it or squish it, and we would have the oil in a perfectly functional form. You cannot say the same about so-called vegetable oils. Now, vegetable is a misleading term because there's nothing vegetable about them. They're seeds. These are refined seed oils. It's soybean

oil or corn oil, the kernels of the corn, and those are seeds. It's safflower or canola. So these seed oils, you crush those and all you're left with is a messy pulp. Then you have to go through a series of steps in order to get the oil. What's interesting about the vegetable oils or what's noteworthy about them is the high amount of a particular fat called linoleic acid. And linoleic acid is unique because of how readily it can undergo a process called peroxidation. And that's what's problematic. When the fat has undergone this process of becoming a radical is capable of now eliciting substantial oxidative stress. Whereas the more saturated the fat is, the more stable it is,

the more resistant it is to undergoing any process of peroxidation. That is not the same with linoleic acid, the main fat from the refined seed oils. In fact, it undergoes peroxidation so readily, which is another way of saying it's become rancid, that you don't know, you can't smell the rancidity when you open your bottle of vegetable oil because very often they've added

deodorizers. I say very often, I think literally all the time, that they've undergone a process of deodorization in order to mask the rancidity of it. They're so likely to spoil or undergo peroxidation that they have to take steps to mitigate that or otherwise no one would ever buy them. But because of things like subsidies and because of the successful war on saturated fat, that became pervasive in our food system. Now, there are others who are seed oil focused. I'm familiar with seed oils to the degree that I've described now and indeed a little further than I'll go into, but there are those who really are more familiar with that area of science than I am.

So as much as there's a great fervor on seed oils right now, I approve that. I think it's appropriate. I am not the voice of that. Now I'm the voice of all the refined starches and sugars. To my great delight, those two always come together. So as much as I'm now defending fat with a little nuance of, but be cautious with the seed oils, as much as someone says, okay, now I'm going to be careful with seed oils too, you actually are already. If you're listening to the first thing I'd said, which was

control carbs and avoiding carbs that come from bags and boxes with barcodes, you're already doing that. Because that is where we get these seed oils. That is the main oil, that is the main fat in all of these processed foods. Indeed, soybean oil is the main fat that is consumed by humans worldwide now. And it's because it's not because we're drinking soybean oil. It's not even because we're eating French fries that are fried in soybean oil, although they can be. It's because of all of the processed packaged carbohydrates that we're eating, that main fat is these refined seed oils. And so by controlling carbs and cutting out the processed bagged packaged starches and sugars, you're usually addressing the hope of diminishing seed oil consumption at the same time without knowing you're doing it.

So then if you are controlling carbs and then increasing fat, again, the ones that you would consider healthy, then this is a formula for a better insulin response. If you are not controlling carbs in an effective way, is it still okay to have higher fat content in what you eat? That's a great question. I don't think so. No. In fact, high carb, high fat is an extraordinarily effective way of getting really fat. Because this is going beyond the conversation thus far, and it's such a big topic that I don't want to hijack the conversation, but it starts to touch on the discussion of what makes fat cells grow and shrink. And I think I can explain it very, very succinctly. And just to help impress upon people, if I hope to claim any authority, Jonathan, on any topic, it would be the fat cell. I understand fat cell biology probably better than most people that

anyone will ever talk to. That is the cell type we focus the most on in my lab. Right now, down the hallway in my lab, my students are literally growing fat cells in petri dishes. We pull fat tissue from human volunteers doing fat biopsies. We're getting the fat samples from animals that have undergone various therapies So what makes a fat cell grow? There's two components and most people only think of the calories But the calories are only relevant in so far as the fat cell knows what to do with them So to say all that another way elevated insulin is what tells the fat cell to store energy

But the signal alone isn't enough. That's where the calories come in. So if insulin tells the fat cell to grow, the fat cell will say, ah, okay, now I know what to do with these calories. I'm going to store them. But just to put a very fine point on it, if someone has low insulin or none, it does not matter how many calories you eat, it is literally impossible. And I know the term literally is used too liberally nowadays and I don't mean to use it that way, I mean to use it very precisely.

It is literally impossible for a body, any animal on the planet, if insulin is zero, it cannot store fat. Any other hormones can be doing whatever they want, calories can be through the roof and it is literally impossible. Like, for example, a person with type 1 diabetes. Some learn and are sufficiently tempted by the fact

that if they eat, they can eat whatever they want. And if they deliberately underdose their insulin, they will be as thin as they want. It is impossible for them to gain fat and keep any fat. Now, there's a metabolic storm raging in their body. Right, right. they will be as thin as they want. It is impossible for them to gain fat and keep any fat. Now, there's a metabolic storm raging in their body because of it. I hate the idea of anyone doing this,

but it is an absolute fact, well known enough to have earned its own name, which is diabolemia. So the growing and the shrinking of the fat cell matters tremendously. Back to the point you'd made, high carb and high fat, ooh, that's a wicked combination.

Because then the carb is going to push out the insulin to counteract it. Exactly. And it's going to open the door for everything to come into the cell, basically. That's right. Yeah. So to be frank, because of that fact, when I elucidate the steps of managing macronutrients, I actually don't go to fat next. I go control carbs, then rather than don't fear fat, I insert the other macro in between them. And I wanna talk about that other macro, but there's one last question that I have around fat,

and that is if somebody is, by the time a lot of people reach the middle season of life, many of them had testing that comes back showing that they have, quote, a high cholesterol hyperlipidemia. What's your take on if you've been told, like your, like whatever the cutoffs are for the numbers for you to get that diagnosis of then actually saying,

and I'm still gonna have more fat in my diet? Yeah, my view is that of a biomedical scientist and not a clinician. So this is such a heated topic that I just want to remind everyone that I'm not giving any clinical advice. I'm just your friendly neighborhood scientist. I know, I don't even need to say that, but I feel like I do because it is so polarizing here. And what I'm going to say is upsetting, which is that I think LDL is one of the worst markers ever relied

on for heart disease. And I can certainly defend this with evidence. Like a paper was published, one among many papers, this one's just particularly telling, it looked at almost, I think, 200,000 patients who had come to the UCLA hospital with a heart attack. That's a lot of people. It was like 190-some thousand people. And they looked at their LDL cholesterol levels

and it was a total bell curve. And in other words, there were just as many people coming in with a heart attack that had high cholesterol as there were who had low LDL cholesterol. LDL wasn't even the least bit predictive and you see this across multiple lines of evidence. LDL just does not sync up nicely with heart disease. And that's important because in some people, not everyone, eating more saturated fat can increase LDL. Indeed, that was like a critical linchpin to the entire seven country study that I described minutes ago. It was the thought process of high saturated fat increases LDL cholesterol in LDL cholesterol somehow magically and I say that somewhat emphatically because there's no known mechanism

that explains this. It's just we now skip a few steps and LDL cholesterol causes an atherosclerotic plaque and the plaque closes the blood vessel and now you have a heart attack because the blood isn't flowing to the heart muscle anymore. But I really do need to just emphasize the fact that there is no clear mechanism even now that it can explain the definitive steps whereby LDL cholesterol causes the plaque. It just sort of is some hand waving and now we have a plaque. But what syncs up much better than LDL cholesterol is triglycerides, in particular. That's one of the reasons why I mentioned it earlier. And triglycerides are remarkably subject to the consumption of refined carbohydrates. That you can see a person who starts eating multiples more saturated fat,

Dr. Jeffrey Volek at Ohio State, The Ohio State University, published a paper on this that as he cut down carbs and was increasing saturated fat, triglycerides were plummeting as the carbs were going down. Which is the exact opposite of what you're often told. Yeah, at that superficial level, you think, well, wait a minute, if I'm eating more fat, how can my triglycerides be going down? It's because people don't often appreciate what the main source of triglycerides are and that's the liver.

Much of what's measured as triglycerides, in fact, all of what's measured as triglycerides, in fact all of what's measured as triglycerides in a fasted state is what the liver is producing through a process called de novo lipogenesis. And guess what humble hormone stimulates de novo lipogenesis? Well, it's insulin. Insulin, right. Yeah, it's because insulin wants to tell the liver, hey, we need to be storing energy. And so the liver, the ultimate at the nexus of all nutrients, the liver will say, okay, well, the best way to store energy is as fat. So I'm going to take all these carbons including glucose and I'm going to turn it into fat

in the form of triglycerides and that's going to be transported through the body in the triglyceride-rich lipoproteins like VLDL or LDL and then that's going to be stored anywhere else in the body. So what primarily drives triglycerides isn't the fat we're eating, but it is in fact the carbs in so far as they spike insulin. Yeah, so interesting. So the big story here is really whether fats are potentially, have the, hold the potential to be in any meaningfully way harmful is more related to the the potential to be in any meaningfully way harmful is more related to the consumption of carbs like during a similar window because that is what spikes insulin and then sort of opens the door.

I would argue, yes. Yeah, especially in the case of the natural fats like the animals and fruit fats, whereas of course the seed oils, you know, they're their own. It's a whole different thing. Yeah. They're their own problem. Let's talk about that final macro protein. You brought up a claim earlier that has been made over the years, China study and other

studies since then. Oh. And I know there's a lot of controversy around that study in particular that you should avoid red meat. We all need a certain amount of protein. Avoid red meat, get most of it from veggies or fish. What's your take on protein here? Yeah. Yeah. most of it from veggies or fish. What's your take on protein here? Yeah, yeah, yeah. So I do think the China study is a travesty of misinterpreted data. I try to say

that with some respect and to be in all sincerity, I don't mean that just as lip service. I do think it was an instance of a message that was determined to be told and the data needed to tell that message because upon further scrutiny the message does start to crumble. But that is a problem when the story relies on correlational evidence, which the China study did. So I reject completely the idea that dietary protein is a primary driver of cancer. Totally and utterly reject it. I do not think that's supported in any meaningful way as a scientist. I think that interestingly, our vilifying of animal protein is again, probably contributing to more problems than we expect. So I typically will say now that we have

all three macros outlined, I start with control carbs, then I say prioritize protein. And then the third part of this is important, which is don't fear fat. Usually, I mean with control carbs, then I say prioritize protein. And then the third part of this is important, which is don't fear fat. Usually, I mean don't fear the fat that comes with protein because in nature all protein comes with fat. And I think there's something important about that because in human studies we see that when a person eats a given amount of protein there will be a certain amount of following a workout, a given amount of protein, there will be a certain amount of following a workout, a certain amount of muscle protein synthesis that has occurred at a microscopic level. When you eat

that same amount of protein but coupled with fat, you have even more muscle protein synthesis. So the combination of the two is more anabolic than just protein alone. Part of this could be a result of digestion, that when you eat protein alone, we don't digest it as well as when we eat it with fat, because when we eat fat, we have the secretion of bile. And bile actually accelerates the actions of proteolytic enzymes or the enzymes in the stomach that are involved or in the intestines that are involved in digesting proteins. So the dual consumption helps us digest the protein better. That's how we should take it. And again, I don't think it's an accident that in nature,

there is no exception, literally none. Every protein in nature comes with fat. Now, that naturally may make some people think about plant proteins. Well, plant proteins don't come in nature. We have to make them. Plants are so devoid of protein by and large that we have to concentrate the plant and then we start getting some messiness that we have to account for. For example, if someone wants to get protein from peas or pumpkin seeds, those are so devoid of amino acids that you have to concentrate, let's just say 10,000 peas in order to get a serving of amino acids. Not only will you probably not get all of the amino acids you need, but you would from any animal fat, literally any

animal fat, you get all the amino acids or any animal protein with its fat. But you concentrate 10,000 peas or pumpkin seeds to get a serving of protein from the plant. In the process of concentrating the protein or the amino acids, you end up concentrating things you do not want. Two things in particular, heavy metals which are known to be at higher levels, potentially harmful levels in plant proteins because plants naturally enrich themselves with some minerals and metals. And they're not meant to be concentrated like we've just done in order to get something as unnatural as a full serving of protein from something as

protein deficient as peas or any kind of seeds or something. So we can concentrate metals like lead and arsenic to unhealthy levels. And at the same time, we end up concentrating things called anti-nutrients. Now, lest anyone think I'm just making up a term to be dramatic, I certainly don't avoid being somewhat dramatic because I teach undergraduates and I need to keep them interested.

So I don't mind being a little colorful in my language. Anti-nutrients are real molecules. They are real chemicals that by design perhaps are intended to discourage us from eating the plant. And what they do is disrupt our ability to absorb certain nutrients. So the great irony is that while we are getting these amino acids from peas, for example, with them is coming some anti-nutrients like trypsin inhibitors or tannins or oxalates or phytic acids, some of which actually directly antagonize or inhibit our intestine's ability to absorb those very amino acids that we're trying to get.

And those that aren't compromising our ability to absorb amino acids or compromising the ability to absorb other things like calcium or magnesium, these very essential minerals that we need. In various ways, trying to craft a diet that has the human relying on plants for protein is a wonderful way to probably, in a way that we haven't even described, drive an autoimmune condition or at minimum have a very poor nutrition and very likely you're increasingly nutrient deficient. In fact, that's a statement I'm very comfortable making. The more a person is avoiding eating animal-sourced foods, the more nutrient deficient they're going to become. You mentioned earlier in the conversation that actually the preferred fuel source for

your brain is not glucose, but it is ketones, which brings us to the topic of ketosis or ketosis diets. And again, this is one of those areas where there seem to be very strong opinions on both sides when it comes to the idea of insulin resistance and ketosis. And ketosis is a way to potentially help manage or even transition from insulin resistance to insulin sensitivity and then potentially really help with all the different conditions that you described earlier. What is the role of ketosis in this, if at all?

I always approach this conversation very carefully for the reasons you just mentioned, which is it's an extraordinarily polarizing subject and people bring a lot of baggage to the topic, which is incredibly unfortunate, to be perfectly frank. As a scientist who uses ketones as an experimental intervention, the number of papers that continue to stack up in defense of ketones is actually difficult to keep track of. And I do that as part of my career. It is that area of research is exploding in a pretty remarkable way. What used to be considered metabolic garbage is increasingly known to be an extraordinarily

relevant and beneficial molecule in the body. So while I don't ever intend to beat the drum of advocacy saying everyone needs to be in a ketogenic diet, that is never my intention. I will defend it because the evidence is so striking. Now, with regards to insulin resistance, which is part of how you framed all of this, a ketogenic diet is extraordinarily therapeutic. We published a paper in collaboration with a local clinic where we found that over 90 days that was sufficient without ever a single injection or medication in humans that the type 2 diabetes was completely gone. No evidence of it whatsoever. Every clinical marker of the disease

had gone to a normal range all by just basically giving them education on how to adhere to a ketogenic diet. And now, someone may even be wondering what is a ketone. A ketone is nothing more or less than a molecule of fat burning. That when the body is burning a lot of fat, it starts to create ketones. That's where the ketones come from. It's specifically the liver is burning a lot of fat and it starts releasing ketones. Now, importantly, the connection that that has to a low carb diet is that you can only burn fat to that degree when insulin is at a lower state. And you're only going to do that by fasting or avoiding dietary

carbohydrates. So a low carb diet can get low enough or a fasting protocol can be long enough to get into a state of ketosis. And again, it's going to be because whatever you did was ketogenic. So a ketogenic intervention will increase ketones. Now, ketones can get too high where they become acidic to the body and very lethal. For example, the diabolemia that I've mentioned earlier, if a person is not injecting insulin and their insulin is essentially at zero, they will be burning so much fat, which is itself a reflection of the impossibility to store fat, that they can't stop burning fat and you start to see the ketones get into a realm that it starts to affect the pH of the body.

Importantly, the average individual can never get that high. You and I, Jonathan, were not type 1 diabetic. We could fast for two weeks straight, drinking water and eating minerals and vitamins, and we would never even start to catch a whiff of ketoacidosis. You cannot get that high in a normal healthy person. You just get to a state of ketosis, which is a very natural, normal state. Anyone who's fasted even 16 or 20 hours likely got into a state of ketosis to some degree. It's perfectly natural. Indeed, some evolutionary biologists suggest that one of the reasons humans departed from other primates on the evolutionary chain is because of ketosis and it fueling substantial brain growth. I encourage anyone

to look up the work of a scientist named Stephen Kunane, C-U-N-N-A-N-E. He's really elucidated that view as one of the theories of human evolution. Anyway, ketones have received a very bad reputation and it is not at all earned. I defend them and I only advocate them in an instance of actually what we discussed very early in our conversation, namely neurological disorders. The degree to which a person can totally stop a debilitating neurological disorder with just by going into ketosis is remarkable to me. That includes say migraines and that's on my mind because I have a colleague down my hallway. He once heard me mention this fact before and into ketosis is remarkable to me. That includes say migraines and that's on my mind because I have a colleague down my hallway. He once heard me mention this fact before in just

a casual passing conversation and then I saw him sometime later and he said, Ben, I have to say thank you. I would get one debilitating migraine headache a week. I decided to try out a ketogenic diet based on something you'd said and I have not had a single migraine in six months. That was the first time in my whole life. Since I was a boy, it's the first time I can ever remember not having a migraine headache at least once a week. I mean, it's changed his life. In fact, just as a point of interest, the oldest published biomedical evidence on the use of ketogenic diets was actually as a therapy for migraines. So it's only in those neurological instances where I advocate the ketone. In every other instance, I would just consider it kind of

icing on the cake, if you will, where it's just a plus that as you're controlling your carbohydrates, you're prioritizing protein and you're not fearing fat, you may be in a ketogenic state, and then welcome to it. You're going to probably feel better for it. I don't present be in a ketogenic state and then welcome to it. You're gonna probably feel better for it. I don't present it in a advocacy for ketones perspective. Right, no, it is really fascinating. We had Chris Palmer in conversation a little while back. He would be a very good one to speak about this. Yeah, and the work that he's done on ketosis

and especially like really, really severe mental illness, schizoaffective disorder, and And the quote remission that he's seen through diet after literally every medication has failed is stunning. And again, neither of us are clinicians. We're not advocating this, but the research is really, really fascinating when it comes to both neurological disorders and also mental illness and the thing that so many people are struggling with these days. And it sounds like, certainly, the two major ways that this would, we would get into that state are reduced carbohydrates and or some version of fasting or intermittent fasting. Yeah, that's exactly right. Yeah, those, fasting is the fastest way. But of course, fasting has to end at some point. And I just

feel inclined to make some comment on fasting. In the midst of all of the enthusiasm and much of it well earned, I feel inclined to just share my view which is the way you end a fast matters more than how long you fast. With the view that you're gonna just roll up your sleeves and jump into a 48-hour fast, okay, but what's most important is what you eat when you're done. I would rather see personally someone only do a 24 hour fast, for example, but have a very well controlled meal that fits all of the managing macros ideas that we outlined earlier rather than fast longer than that and then get into disordered eating. And that is how it can be in some people where the fasting is their own version of binging and purging.

No, that makes a lot of sense. I'm someone who's done a lot of different forms of fasting. I've noticed the way that you get both into and out of it, it really makes a difference. Both in the way you feel and imagine, if you literally looked at what was happening internally, it would make a big difference also. Let's talk a little bit about one other really big behavioral change

that really plays into what can we do about this and that is exercise. Two major categories pop into my mind, resistance training and cardiovascular exercise. How do we think about these two things in the context of helping to rebalance insulin? Yeah. I'm an enormous advocate of exercise and while there is certainly something to be said for differentiating between the two, aerobic versus resistance or strength training, my general answer is the most important or best exercise is the one you'll do. Now, insofar as a person has the ability and any hint of an inclination, I actually prefer

and indeed advocate strength training over aerobic training. That's just because of the value of muscle mass. Muscle is such a great defender of metabolic health because it's so big and so hungry. It wants to eat blood glucose and does so very readily. In fact, you'd mentioned the continuous glucose monitor earlier. 80% of where that glucose goes when it's on its way down is by going into muscle, assuming a person has a decent amount of muscle mass. So muscle is the lion's share of glucose. And importantly, during the exercise time itself, even a person who's very insulin resistant, the working muscle has its own way of getting in that glucose. So at rest, if a muscle is very insulin resistant, insulin is coming and knocking and trying to open the doors for the glucose to come in and yet the doors aren't really opening very well.

Once the muscle starts to exercise, those doors open without the need of insulin to come and tell them to. So the magic of the exercising moment is that insulin is able to come down, which it does during exercise, and at the same time, the muscle is still able to readily consume, indeed, better than ever, any of the glucose from the blood, which is helping control blood glucose, which in turn is helping control insulin. When you think about resistance exercise, I think I've heard you talk about this before, correct me if it's not right, because a lot of people are like, what do I do? How much?

How frequent? How intense? The one thing that I've heard you really center on is, okay, you can talk about all that stuff, but the fundamental thing here when you're talking about resistance is really that whatever it is that you do, you do to failure. Is that right? And if so, why? Yeah, definitely.

If not all the way to failure, there's evidence to suggest that if you get like one or two reps away, then it's still just as good. But you need to feel that burn. You know, it sounds cliche to say this, but you want to feel like that muscle is about to be done, because that is the best way to stimulate. That's the best way to signal the muscle that it's time to grow. That's sort of analogous to insulin being the signal for the fat cell to grow than amino acid, than fat fueling that growth. When it comes to the muscle, it's the near failure movement stimulates or signals the growth and then it's the good amino acids and even fats that fuel that growth. And just to describe the two of those characters in a little more detail, the amino acids are providing the protein structure within the cell and then the

fats are providing the structure of the membrane. Good luck blowing up a balloon or expanding a balloon if you don't have the ability to make the membrane of the balloon get bigger. So as much as we're trying to expand the size of the muscle, we need to both consider what's building in from the inside and what's allowing the expansion from the outside. That's where a lot of the fats come into play. So then resistance training is critically important in part because it takes up a lot of the glucose, also because over time through hypertrophy, you have more of that mass or you have more of the engine to actually consume it and keep a better balance. So when we talk about then aerobic exercise or even walking, so many people now these days, they're trying to quote, hit their 10,000 steps. Walking, I would imagine, it matters because you're using your muscles in some meaningful way. Those muscles are going to need some sort of source of fuel. That fuel is very likely going to come from glucose if it's readily

available in the system. So, okay, so it helps balance the insulin. But it seems like not as important in terms of actually sustaining or building the actual mechanism of glucose consumption. No, no. I mean, you'll have that acute benefit benefit but then the long-term sort of at-rest benefit will be mitigated. You know, like when you actually sit down to eat you're not really getting as much benefit. Now I would hate for someone whose only activity is to go on a brisk walk now hear me say this and think well then fine I won't do that anymore. Yeah sure, I mean it's so much better than nothing. Yeah that's right, yeah I mean the most important exercise and the best

is the one you'll do. Right. So as much as I am hopefully making the case for some strength training, if you just hate doing it and you know you won't do it, well then just do the one you're doing. Now that makes a lot of sense. I want to touch on one last area here before we wrap up. And that's stress. So I have worn continuous glucose monitors on and off over a period of years and noticed that the level of my glucose seemed to be sometimes fairly dramatically affected

by what I would perceive as stress without changing anything about the way I'm eating like where I Would look at it and I would open my eyes first thing in the morning. I hadn't moved I hadn't eaten anything. The only thing that changed was I was awake and maybe I had a day in front of me that I was a little anxious about or that I could – even if it was low grade, I could tell there was a little bit something going on and I would look at this slow climb on my glucose. Is that relationship real? And if so, does that also implicate insulin? Oh, yeah. Yeah. In fact, what a delightful thing. So what you've managed to do now by accident or by intention is we've now covered with the inclusion of stress

all three of the main causes of what I call fast insulin resistance. So yes, stress hormones, and that's how I define stress as a professor of endocrinology in part, it's the stress hormones, namely cortisol and epinephrine. Cortisol and epinephrine, while both being considered stress hormones, have almost nothing in common. They have different origins, they're synthesized differently, they come from different cell types, they move through the blood in different ways, they act on cells in different

ways. The one thing they have in common is that they both dramatically stimulate an increase in blood glucose. Epinephrine does it very, very quickly. Cortisol does it a little slower, but a little longer. But that is the one thing they have in common and that's it. They have, I think, literally nothing else in common. So yeah, whether it is a little bit of a rough night of sleep, that elevated cortisol in the morning and then later is the elevated glucose is because of the elevated cortisol. When you then try to correct that poor sleep by consuming more caffeine and then you have higher epinephrine, that's also going to increase your blood glucose. So yes, without a doubt, rapidly, if you increase the stress hormones, you're going to see hyperglycemia. At the same time,

both of those stress hormones cause insulin resistance to varying degrees. Cortisol does so a little more stubbornly than epinephrine does, but there is human evidence to show that if you increase the cortisol, give them an hour or two, they're going to have insulin resistance. Increase the epinephrine, give them an hour or two, they're going to have demonstrable insulin resistance. So yeah, anticipating that mental anxiety and the sleep deprivation, that's a stressor. Indeed, it's the one that I claim is the most relevant. And then some of the interventions that we do to try to address those two things and more also compound the metabolic consequences of stress. So share one or two of the interventions you might focus on. Like caffeine, which is one I'd already mentioned.

Okay. Some of the things that we do to kind of counter the idea. Got it, got it, got it. It is so interesting, right? Because I think so often we're like, okay, so I get what's going on here. I get the science, I get the argument. Okay. And it seems like A, nutrition plays a really big role and B, movement plays a really big role, sweet. I can do that. I can commit to a different way of eating.

And then we live this wildly stressed out lifestyle where we're just being barraged all day. And we're just like, well, that I just have to deal with. And it's not such a big deal. And I think what you're describing is this is actually a big part of it. If you do everything else, but you're still in a circumstance

perpetually where the stress elements in your body are just chronically high, we've still got a problem. Yeah, in fact, I would say as much as we've just touched on these three primary causes, too much insulin, inflammation, and stress, one of the reasons I focus on the too much insulin a little more than the other two is one, I think it is the more common cause, but it's also the one that is easier to leverage in our favor because it's so obviously connected just to dietary habits. Whereas inflammation, if someone has inflammation

driving insulin resistance, it can be difficult to know what the cause of that inflammation is and even harder to know how to turn it down. Stress, the more we tell someone that they need to control their stress, paradoxically, the more stressed they may become. So it's just a harder – those are hard levers to really grasp the inflammation and the stress, as important as they are. And I think it's in our best interest to find ways to try to grasp them and turn them down. The high insulin lever, boy, we can firmly grasp it. And while the change in dietary habits is not necessarily easy, the approach is at least

simple. This has been incredibly helpful. I'm so excited to dive into more of this work. I always wrap with the same question, which is in this container of Good Life Project, if I offer up the phrase to live a good life, what comes up? I like that question. My answer to that is focus on my family. That as much as I've just spent an hour and a half with you and all of our best friends here talking about my role as a scientist, that is to me a means to an end. End is how can I be the best husband and father? So to live a good life for me is to remember what matters most and just remember that no success in my life will compensate for failure in my home. And so be a very devoted

husband and a very loving, kind father. That to me is a good life. Hmm. Thank you. Hey, if you love this episode, say that you'll also love the conversation we had with Dr. Gabrielle Lyon about maintaining and building muscle through nutrition and exercise. You can find a link to that episode in the show notes. This episode of Good Life Project was produced by executive producers Lindsey Foxx and me, Jonathan Fields. Editing help by Alejandro Ramirez and Troy Young. Christopher Carter crafted our theme music.

And of course, if you haven't already done so, please go ahead and follow Good Life Project in your favorite listening app or on YouTube too. If you found this conversation interesting or valuable and inspiring, chances are you did because you're still listening here. Do me a personal favor, a second favor, share it with just one person. I mean if you want to share it with more that's awesome too, but just one person even, then invite them to talk with you about what you've both discovered, to reconnect and explore ideas that really matter, because that's how we all come alive together. Until next time, I'm Jonathan Fields, signing off for Good Life Project.