The New Paradigm Of Insulin Resistance – Top Nutrition Researcher Alex Leaf, M.S.

Content By: Ari Whitten & Alex Leaf

In this episode, Alex is back for part 2 of our myth busting discussion—be sure to listen to our conversation from last week if you haven’t already!

Before you dive into this episode, I want to tell you that this is a powerful podcast – especially if you’re overweight or if you have insulin resistance/type II diabetes. 

Alex and I thoroughly discuss the research and ideas we’ve been compiling for over 2 years, and he presents a novel and evidence-based paradigm of metabolic health and insulin resistance (which are at the core of many of the chronic diseases that kill us)…one that may just change your health forever!

Why does this matter? 

9 out of 10 people in the United States (or possibly even higher) have poor metabolic health. And these issues are connected to heart disease, cancer, and neurodegenerative disease…the major killers faced by everyone in modern society. 

(Quick note: As a reminder, we’re still offering The Fat Loss Blueprint for $200 off the regular price of $497. Alex and I collaborated on creating this program, and it’s no gimmicks, no hype, no BS, rock solid, evidence-based guide to advanced fat loss strategies. Use the coupon Alex upon checkout!


Exercise increases glucose transporter expression independent of insulin (
Glucose moves passively into pancreas and promotes insulin secretion (
Fat cells can only store so much fat before they shut themselves off from energy (
Some people can make more and more fat cells and become really obese before metabolic problems occur (
Metabolically healthy obese people are at an increased risk of developing metabolic diseases years later (
Evidence for fat loss reversing type 2 diabetes  (
Some can’t restore normal metabolic health after having diabetes for a long time (
Intermittent fasting allows pancreatic cells to regenerate (

Table of Contents

In this podcast, Alex and I discuss:

  • A clear and practical answer to the question: What is metabolic health?
  • Are blood tests the best way to measure metabolism…or the health of any system? The top signs of poor metabolic health that you should be aware of
  • Does insulin make you fat like everyone claims it does? 
  • Why type 2 diabetes is connected to every other chronic condition like cancer, heart disease, and neurodegeneration like Alzheimer’s 
  • Why even most functional clinicians get the idea of high blood sugar and insulin resistance wrong…and why this mistake might actually worsen your metabolic health
  • The shocking reason why Alex recommends a low-carbohydrate diet for people with diabetes!
  • The ancestral role of CHO in the human diet and why carbs are one of the most evolutionarily appropriate foods we can eat
  • Why our biochemical view of health has left us sicker than ever and the crucial mental shift we must take to build true health!
  • The most important player in insulin resistance that NO ONE is discussing…Alex provides practical solutions to avoid metabolic disease, obesity, and resilient health
  • A brand new way to understand the connection between obesity, fat cells, and insulin resistance…it’s not as simple as too many carbs or imbalanced hormones
  • The fascinating technical reason why modern foods ruin our metabolism and make us sick
  • The scientifically PROVEN, real solution for diabetes and how to implement it today!

Listen or download on iTunes

Listen outside iTunes


Ari Whitten: Alex, welcome back.

Alex Leaf: Yes, I’m happy to be back, man.

Ari: I think this has got to be number seven or so at this point, maybe number eight. For those that don’t know, hopefully you’ve listened to some previous podcasts where Alex has been on the show, but Alex is someone who works very closely with me on all of our writing projects on program development. He’s the co-developer, and I would say actually the main developer of the Fat Loss Blueprint Program, the Advanced Fat Loss Strategies Program that we co-developed together a year or two ago, something along those lines.

This is really a no frills, no gimmicks, no BS, no fad diets, no crazy wacky promises of 30 pounds of weight loss in four weeks and whatever other BS that’s out there. This is really just a collection of the most rock solid advanced fat loss strategies according to the scientific evidence circa 2023, 2024. It’s a phenomenal program. I’d highly recommend everybody check it out. It’s available right now in honor of this two-part podcast that we are doing right now with Alex.

We’re putting it on sale for $200 off the normal price so you can get it for 297 instead of 497. There’ll be a link below or you can go to and go to programs and get it there. That offer will just be available for the next week. Check that out if you’re interested in fat loss. Alex is also a co-author on my most recent book, Eat for Energy. In general, in terms of formal credentials, he’s got a master’s degree in nutrition. He’s one of the most well-read. He’s got a very special brain.

He just holds on to scientific studies in his mind and they’re just locked in for years. Maybe you’d call this a photographic memory, but it’s something along those lines where he stores information in his brain better than 99.99999% of people. He has become just world-class in terms of nutrition knowledge, in terms of understanding many aspects of physiology. I value him tremendously and I’m very grateful for him as a co-author and co-developer of my books and programs.

He’s just been a joy to work with for the last five or six years. I have enormous respect for his expertise, which is why he’s here yet again on the podcast to deliver some of that expertise to all of you. What I wanted to chat with him today about is one of his areas of expertise, which is understanding the science around insulin resistance and diabetes. A lot of this discussion is really at the center of so much of the modern disease epidemics, the diseases, what are called sometimes the diseases of civilization or the diseases of nutrition and lifestyle or the chronic diseases of aging.

These are diseases that are largely driven by nutrition and lifestyle. This represents over 80% of the chronic disease burden. Eight of ten of us will die from diseases of civilization, diseases of nutrition and lifestyle. Again, at the center of these diseases, things like heart disease, things like dementia and Alzheimer’s, cancer, chronic kidney disease, and not every type of cancer, but I would say a large majority of the types of cancers that you can get, and many other diseases that are major killers for us are at the center of this is this story of metabolic health, insulin resistance.

Metabolic health – an overview

Understanding this in the proper way. I think as you’ll hear Alex talk, you’ll slowly come to realize that I think, and certainly he thinks that many people are not understanding this in the right way in terms of how we view the root causes of these problems and how we view the solutions. With that said, Alex, give people an overview of, maybe I’ll let you decide how you want to introduce this, but this topic of metabolic health, people have heard that phrase before, but maybe I would bet a large portion of people don’t actually know what metabolic health means. Then maybe introduce the idea of insulin resistance and blood glucose control in that picture.

Alex: Yes. The way I would want to start describing metabolic health and the way I think it’s most accurate is metabolic health basically refers to your ability to handle energy. I want to very quickly emphasize the importance of the word energy there because I know that there are many people who have a visceral dislike of the idea of calories. In fact, I’ve heard people make arguments about calories are just energy. They aren’t related to your body mass. You need to be more concerned with like your fat balance. How much fat you’re losing versus how much you’re putting on.

While I don’t necessarily agree with that, the idea of fat balance makes sense. Fundamentally, energy is what matters because everything in our body, every physical structure, and all the food we eat contains potential energy. It all contains energy that our body, our enzymes work to then break down, transfer, use to transform matter into other matter. This is fundamentally how our bodies work and how every living organism works, is you take energy and you use it to manipulate the matter in your body. The two things are equal, by the way.

I want to emphasize Einstein’s famous equation, E equals MC squared stands for E energy equals mass times the speed of light squared. You can actually equalize energy to mass. They aren’t two totally separate things. They can go back and forth, and that’s what happens in our body. Metabolic health is your ability to handle energy efficiently. That means when you get energy from the food that you eat, because we need to eat to survive, we’re not plants, we can’t rely on sunlight exclusively. Then what does our body do with it?

How efficiently is our body able to take that energy, absorb it from our digestive tract, transfer it through our bloodstream to all of the different organs and tissues that need it, and then either use it or store it? How well does that happen? Then the reverse. When you aren’t eating, how well is your body able to sustain yourself and give you a thriving life, relying on the energy it has previously stored? That’s what I think metabolic health is. People who have great metabolic health, they can eat a lot of food. They’ll have a healthy body composition with very robust tissues that are able to do their job effectively of either burning up the energy or storing it for later.

Then they’re able to take that energy when they’re not eating and effortlessly feed it from their storage depots into the organs and tissues that need it without there being any hiccups that could inhibit function. A lot of people just, I would say colloquially, people will say like, well, when you fast for longer than an overnight fast, do you get hungry? Do you have brain fog? Are you fatigued? These are all signs that your body isn’t efficiently able to draw upon its own energy stores. Then use that energy to keep you going.

Whereas somebody with more robust metabolic health will wake up. They’ll have lots of energy. They’ll have a desire for movement. They’ll have more things that historically would give us food-seeking behaviors because you can’t be lethargic and brain fogged if you need to go hunt to get food. If your body’s working optimally, you’re going to be zoned in. You’re going to have higher stress hormones that are going to facilitate that process.

You’re going to have more energy often until you eat. Then things will level out. People with poor metabolic health when they do eat, they experience problems with blood glucose, blood lipids, energy storage systems are dysfunctional. Their mitochondria can’t use the energy effectively. They’re fatigued all the time. They have brain fog. They can’t think. People with good metabolic health have the opposite.

They think great. When they eat, they get energy from eating, but they have energy also when they don’t eat. There isn’t any of these ups and downs, and I would say that’s actually another part of it. People with problems with metabolic health after they eat feel crappy. Maybe they have the slumps, they get sleepy, they’re tired. It’s because their body’s not responding appropriately to the food.

The potential effects of Diabetes 2 on long term health

Ari: I might want to actually circle back to something that you’re describing here, which I think is interesting and worth talking about as we get into this which is there is a tendency that we have in our society, this moment in our culture and the paradigms of medicine and the dominant paradigms of thinking around health, where we would tend to view the way to measure poor metabolic health as doing a blood test and seeing various markers on there.

Maybe, fasting blood glucose and other markers of triglycerides in cholesterol and things that relate to metabolic syndrome, blood pressure and so on. Maybe inflammatory markers are signs of metabolic health, but a lot of the things that you just mentioned are actually macro-level phenomenon that are easily observable in yourself on a daily basis. Do you wake up with a lot of energy? How well do you sustain energy if you go many hours without eating food?

Do you have stable energy levels throughout the day or do you find they dip and you crash every few hours and require food to keep yourself going? How do you feel after eating? Do you have trouble with your blood glucose levels and energy levels after eating and so on? These markers of energy in relationship to periods of feeding or periods of not feeding and so on become what I would argue, are actually probably better indicators of metabolic health than anything that would show up on your blood test. Which I think is related to a lot of the stuff we’re going to get into in this discussion.

Let me have you go to the next step, which is insulin resistance and diabetes specifically. How does that tie into this story of metabolic health? Everybody at this point has heard of certainly diabetes and they probably understand that insulin resistance or this idea of insulin sensitivity and blood glucose levels, high or low in the normal range, are somehow tied into this story of metabolic health. Can you paint that picture for people of how that aspect of the story ties into metabolic health more broadly?

Alex: Yes. First, I guess it’s important to emphasize that there’s two types of diabetes. There’s type 1 and type 2. Type 1 diabetes is an autoimmune condition where your immune cells attack and destroy your pancreatic beta cells that produce insulin. All of the pathology and everything we’re going to be talking about is focused on type 2 diabetes. Type 1 diabetes and type 2 diabetes can’t be compared, honestly. The causes are just wildly different.

For the most part, there’s a little overlap, but if diabetes is based on your blood glucose levels, if you don’t make insulin, your blood glucose rises, and that’s type 1 diabetes. There’s no insulin resistance. Someone could have perfect metabolic health and they would have diabetes because their pancreas is literally destroyed by their immune system. Again, there’s that physical structure breakdown is now causing all of these biochemical things that we like to measure. For most people, 90% of diabetes cases it’s type 2 diabetes, and this is the apex of metabolic dysfunction. It’s the tip of the mountain or the peak of the mountain that you would reach if you let metabolic dysfunction just continue without intervening to stop it.

Ari: Alex, let me have you go one more piece of context. You mentioned that the proportions of type 1 versus type 2 diabetes in terms of the overall pool of total numbers of cases of diabetes, but what about the context of, as far as the proportion of people with diabetes that relates to the total pool of the chronic disease burden more broadly and all these other diseases like heart disease and cancer and chronic kidney disease and dementia and Alzheimer’s and so many others. To what degree is type 1 diabetes contributing to that versus type 2 diabetes?

Alex: Oh man. I would say type 1 diabetes isn’t even on the on the radar with that. Type 1 diabetes–

Ari: To understand. When we’re talking about [unintelligible 00:15:35] more broadly, we’re talking about type two diabetes.

Alex: Yes, type 1 diabetes brings with it a host of problems. It’ll literally kill you if you don’t manage it with insulin. In that case, that’s a necessity to keep you alive. As long as you keep it managed, the rest of your metabolic health, as long as that’s in good shape, you’re at no increased risk of disease. I have several friends that have had type 1 diabetes since childhood and they’re some of the healthiest people I know because they take care of themselves. They maintain strong physical structures in their bodies.

Sorry, amusingly, they all inject insulin out of necessity, but they aren’t fat. Just had to point that out for the insulin equals fat gain people.

Anyway, type 2 diabetes is a leading cause of cancer, cardiovascular disease, and neurodegeneration because once you start having a breakdown of your metabolic health, that affects literally every organ system in your body because now every organ system in your body, your blood vessels, your brain, your muscle tissue, your fat tissue, they aren’t getting the energy that they need, or they aren’t able to use that energy properly, while simultaneously being exposed to more energy than they can safely deal with.

It’s like, man, imagine that, this might be a bad example, but let’s say you had a car and you cut off half of the gas tank, so now you have half the room for gas, but then at the same time, you’re letting gas just overflow the car. It’s two related but separate issues. You can’t use as much energy, which your cells need to function properly and you’re getting so much energy tried to be jammed in them that it’s spilling over and damaging other components. This doesn’t just happen overnight. I want to emphasize this because I think you mentioned earlier that 9 out of 10 people are considered to be metabolically unhealthy in the US.

Ari: I didn’t mention that, but it’s a good thing to mention. There was a study, the one that showed 88% of US adults are in poor metabolic health. Then I saw actually a recent one as we were writing this recent chapter for the book, there was another study a few years later that I think measured it in a slightly different way and they found 94%, an even higher number.

Alex: Yes. In those studies, what they’re doing is they’re taking physical measurements. They’re looking at people’s obesity and that type of thing. Then they’re combining it with markers of metabolic dysfunction, the biochemical markers that we like to measure because it’s easy. They say, 9 out of 10 people aren’t healthy. Now, diagnosed diabetes in the US is at about 12% of the population. There’s another 15 to 20% estimated to be undiagnosed because these people just don’t go to the doctor.

Then everyone else in that difference, so let’s say that’s what, 60% of the population is in between. They aren’t healthy, but they’re not yet at diabetes. You could say, they have pre-diabetes, you could say they have metabolic syndrome, whatever.

Ari: I think it’s important to understand. I think a lot of people don’t grasp the concept that this is really a spectrum that we’re talking about. People, I think, have been taught to think of diabetes or even “pre-diabetes” as well-defined conditions that you either have it or you don’t. Once you have it, then you have this disease that needs to be treated in XYZ way. I personally think, and I hope you’ll explain, I’m going to ask you to explain this, the idea of insulin resistance and sensitivity as a spectrum.

Where we define specific cutoffs to say this XYZ as a disease state is really to a large extent arbitrary but a better way to understand this is a spectrum of optimal insulin sensitivity versus high levels of insulin resistance

Alex: Yes. I think a little later, we’re going to get into the structural breakdowns that cause metabolic dysfunction and diabetes. I’m not going to go into that at this time, but what I am going to say is that fundamentally what’s causing type 2 diabetes to occur, which is the elevated blood glucose, is that there are problems with insulin receptors on cells where they become less responsive and it’s a spectrum. Maybe they’re 90% responsive compared to completely healthy, maybe they’re 80, 50, 30 and it just keeps getting worse and worse.

When insulin isn’t able to bind to these receptors effectively and transmit the signal telling this cell to take up glucose from the bloodstream, then your blood glucose starts to rise or stay elevated after eating. Now, these receptors exist on virtually every cell in the body and depending on where insulin is binding will determine what the effects are. In the case of diabetes, when insulin is binding to muscle tissue or fat tissue, it’s telling those cells to take up the glucose and either use it for energy or store it for later. That storage can be in the form of glycogen in muscle or as fat tissue in your fat tissue.

On somewhere like the liver, insulin’s job is to actually not just tell the liver to take up glucose but for the liver to stop creating glucose from other precursors like amino acids. The primary reason why someone’s fasting blood glucose elevates when they have pre-diabetes or type 2 diabetes is because of the liver. The liver is not receiving insulin signal to shut off its glucose-making abilities and so even when you’re not eating, it continuously pumps out glucose into your blood that it makes from things like amino acids and doctors will see this and they’ll say, “Oh, you’re fasting glucose is high. This is how we’re going to diagnose you with either pre-diabetes or type 2 diabetes.”

Now, do they ever tell you why that’s happening at a fundamental level? No, they just tell you your blood glucose is high and maybe you should lose weight or you should go on a low-carb diet or whatever because your body isn’t handling carbohydrates and glucose in your body properly. Fundamentally, the biochemistry is a symptom of the actual structural defects that are occurring in the body that are leading this to happen.

The conventional view on insulin resistance

Ari: Before we get into that what you’re just alluding to there, let’s go into the standard conventional ways that most people within conventional medical circles, and I would say within natural health and functional medicine circles for the most part, tend to understand the physiology of insulin resistance and the way that they think about causation and treatment. Can you explain how they tend to conceptualize this.

I want you to do it in a charitable, generous way. I don’t want you to misrepresent. I want you to be generous to their perspective presented as fairly as possible. Then after we do that, then I want to contrast it with the new perspective, the new paradigm that you want to present on insulin resistance.

Alex: I’ll do the conventional and then I’ll do what I would consider maybe the more alternative way of looking at it. Both ways actually address it pretty decently. We think that they’re missing some important parts, but ultimately, they’re keeping people alive. What they do, conventional, let’s say you go to the doctor. Your blood glucose is elevated. The first line of treatment from a conventional medical standpoint is to put you on metformin, because what metformin does is they say, “Hey, your blood glucose is elevated. We’re doctors, and so we know that diabetes comes from insulin resistance.”

They definitely know that. They know how it’s caused. They say, “Okay, insulin resistance, so low insulin sensitivity. Let’s give you metformin, which is going to increase your insulin sensitivity and help your body naturally put blood glucose back where it’s supposed to go in your muscle and fat tissue, instead of having it hang out in your blood.” It works.

Ari: Problem solved, diabetes cured, right?

Alex: Maybe, if that doesn’t work because for a lot of people, metformin doesn’t get their blood glucose under control. Maybe it helps a little, but for a lot of people, they might not even have diabetes anymore, but they’re still pre-diabetic. It’s not that they’re healthy, it’s just they’re less unhealthy. If the problem persists, or even if it gets worse, despite being on something like metformin, first they’ll increase the dose.

Once they reach the max dose of metformin, they’ll be like, “You need to go on insulin.” Then they’re just going to have you start injecting more insulin because if you inject more insulin, well, now, you’re going to logically have more insulin signaling at the receptors, and you’re going to force blood glucose away into various tissues.

Ari: I might be jumping ahead here, but let’s say, let’s use insulin, let’s leave metformin out of the picture for a minute. Let’s talk about insulin in the way you just described, let’s say that you used insulin and you used it effectively, meaning injecting extra insulin beyond what your body’s producing. You used it effectively to keep your blood glucose in a relatively normal range to prevent it from being elevated. Does that mean that you don’t have insulin resistance or diabetes anymore?

Alex: It doesn’t have any effect on whether you have insulin resistance or not. From a diagnostic standpoint, you could not meet the diagnostic criteria for diabetes technically.

Ari: That’s a different discussion. I certainly don’t care about that. I care whether there’s an actual problem or not. The ability to measure the extent of the problem based on our diagnostic criteria.

Alex: Here’s the thing too. There’s reasons why your insulin receptors become desensitized to insulin. One of the reasons in a positive feedback loop is that the more insulin you have circling around, the more the receptors become desensitized to it as a protective mechanism, because your cells aren’t stupid. I think cells aren’t just these little robots that just sit there and work in a very fixed manner. They’re dynamic. They’re constantly looking at what’s going on around and within them, and then adapting to that.

When a cell has a problem and it says, “Hey, we have a problem, and this is causing our insulin receptors to not reach the surface,” because we don’t want that to happen. Then you’re going to inject insulin and force more energy into that cell, which is going to just aggravate that problem. That cell is going to withdraw even more insulin receptors from its surface. You’re going to have to continually inject more and more insulin to get the same effect. In a sense, you’re actually going to worsen the original problem, even though the symptoms of the disease seem like they’re in control.

Ari: I want to make the distinction that I think what you’re presenting now, and you’re alluding to the idea that there is an intelligence behind insulin resistance, that it’s not purely the body’s being dumb, and this is a pathology, this is disease, a problem of the body, because the dumb body can’t figure out how to control blood glucose. What you’re saying, which is, I think, introducing a novel perspective that is not typically seen by most people within conventional medicine, and maybe, I don’t know to what extent this is now common among natural health and functional medicine people.

I think in general, in conventional medicine, they see this as a pathology, not as the body intelligently making the cells more insulin resistance to protect themselves. Would you agree with that?

Alex: Yes.

Ari: Okay. With all due respect, I think you’re jumping a little bit ahead in introducing some of the more novel perspectives. I want you to come back to the conventional medical and more typical functional medical ways of viewing the physiology and the mechanisms of the resistance.

Alex: Conventional will say, your blood glucose is elevated. Let’s try and increase your insulin sensitivity using drugs, and if that doesn’t work, we’re just going to try and overpower your body by using hormones. Those hormones are just going to force your body to do things maybe it doesn’t want to. Now, in this situation, the underlying causes are never being addressed.

They’re just being managed because they’re focused on the biochemistry. In a similar way, I would say a lot of alternative practitioners will either use supplements that have effects that are basically identical to metformin, such as berberine, which is the same active ingredient as metformin. Maybe they’ll try—

Are herbal supplements better than pharmaceutical drugs?

Ari: Is it the same actual active ingredient, or is it another chemical that works in a very similar way through the same mechanism?

Alex: I don’t know that, but metformin and berberine, when compared head to head, have almost identical effects on the outcomes to where they could be exchanged dose for dose and have same outcome. They’ll try maybe supplements because they have this idea that, if it’s not a pharmaceutical, then that’s A okay. Drugs are bad, but supplements aren’t, which is a really arbitrary distinction since they’re both concentrated molecules that we use to have drug-like effects in the body.

Ari: I will say, to be charitable to that view, I think, in general, it is actually a good bias to have. I think you can make the argument that you just made that it doesn’t matter whether the chemical that we’re talking about is natural or artificial. However, I think that when we look at the literature more broadly and the way the body interacts with a huge variety of thousands of different natural chemicals and the way that it tends to interact with artificial manmade chemicals, I think we can legitimately say that the side effect profile is as a generalization, tends to be a much higher risk of adverse effects from man-made chemicals as opposed to natural chemicals.

Again, all things being equal, I’m totally aware that there are things in nature that are highly poisonous that can kill you. I think that is a legitimate bias that we can have towards natural stuff as opposed to artificial stuff that I think is legitimate. For example, just as a random point of contact in this discussion. Compare natural scents, let’s say, from strongly scented things from nature, essential oils, flowers, et cetera, wood like Palo Santo wood, that has a strong smell, and things like that.

We compare the physiological effects of those compounds versus man-made artificial perfumes and scents that you would have in an Glade plugin or something. Those things tend to have– we know they have phthalates, we know they have endocrine disrupting compounds in them. As a generalization, those things tend to have, generally, no positive effects and lots of adverse effects, whereas the natural compounds tend to be much more in the other direction.

With heavy doses, maybe you could encounter some adverse effects, but with reasonable doses in the range that most people would get, they tend to only have positive effects. All of that is to just say that there is a reasonable basis for the bias towards natural versus man-made.

Alex: I agree, actually. I’ll just give one more example of that. If you think of sleep medicines, pharmaceutical sleep medicines, basically, make you go unconscious so you’re not actually getting any restorative sleep. Whereas, there’s numerous supplements and you put a lot of them in your sleep supplement that, more so, push the body into wanting to go to sleep and stay asleep rather than just shutting it off completely to go to sleep and stay asleep, rather than just shutting it off completely. Yes, I agree with you.

Ari: It’s also true, to your point, that, in this particular context of insulin resistance, essentially they’re viewing this problem in the same way, they’re viewing the problem and the solution in the same way, here’s this pathology and the body, the body’s dumb, it’s insulin resistant, let’s force it to take more glucose in the cell by using X or Y chemical, X versus Y, one is natural, one is man-made.

Alex: Oftentimes, and this is where I think the alternative route is superior to conventional medicine, is they won’t jump to those solutions quite as readily. Their first-line approach is usually dietary changes and ideally, lifestyle as well. I think in this field, the most common dietary change is to have people go on a low-carb or ketogenic diet. Frankly, I think it’s a good idea. The reason being that elevated blood glucose is directly harmful to numerous organ systems.

If you can rapidly drop that with a ketogenic diet while you work on addressing the underlying causes, because it’s not caused by carbohydrates. It’s just that carbohydrates are what allow the disease to express itself. The analogy is like a celiac disease. If you want to be diagnosed for celiac disease, you actually have to eat gluten for several days before they can do the diagnostic test, because if you don’t eat gluten, the disease does not present.

They can’t say, “Oh, your intestinal cells are starting to be destroyed, you definitely have celiac disease. They can’t do that because without gluten, nothing’s happening. With type 2 diabetes, if you’re not eating glucose and you’re on a ketogenic diet, not everyone, but I would definitely argue for most people, the disease isn’t going to show up. Not because you don’t have it, but because our diagnostic criteria are based on carbohydrates being in the diet.

You could have all the structural problems going on that cause diabetes, but as soon as you stop eating carbs, your blood glucose and your blood insulin rapidly fall because those things are primarily dictated by the carbohydrate content of your diet and your metabolic response to them. That’s the insulin component. I think it’s a good plan to prevent damage while you work to address the issue. Again, you’re not actually addressing what’s causing the insulin resistance to begin with, at least not directly.

Carbs have been part of our ancestors diets

Ari: This is an important distinction because many people will go on a low carb or keto diet and many people who have insulin resistance or diabetes, they’ll go on this diet, their blood sugar is in the normal range and then it’s like, “Hey, I went low carb and keto. I don’t have prediabetes or diabetes anymore. Problem solved.” You’re saying that is not the correct interpretation of that.

Alex: In fact, I would argue if you’re on a low carb diet, eat some carbohydrates. because if you can’t eat carbohydrates in your diet without something going wrong, you’re not metabolically healthy. You can be on that ketogenic diet and think everything’s okay, but you’re masking the problem or you’re avoiding confronting it.

Ari: It’s like I have a bum knee and as long as I’m on crutches and I take the weight off this leg, I don’t feel any problem with my knee. To try to use my leg and walk on that leg by getting rid of the crutches, now I experience that my knee has a problem.

Alex: Yes, exactly. Oftentimes, people eating ketogenic diets are big fans of the ancestral way of looking at things. I think it’s important then too, to emphasize that carbohydrates have been a primary energy source of most ancestral diets.

Ari: Pretty much you can say this, given all the back and forth and all the competing claims for “the diet of our ancestors”. I want to emphasize to listeners, Alex and I can say this pretty definitively, because we have spent a very long time researching this exact question and writing about, in extensive details, the diets of our ancestors.

If anybody’s inclined to question whether we’re biased or they’re skeptical of what we’re saying on this, I would encourage you to look at the work of Staffan Lindeberg, who is a researcher who traveled all over the world and meticulously documented the diets of tribes in Africa, in the South Pacific, in South America, and many places all over the world. There is, of course, variation, like the Inuit diet in the Arctic is very different from the Hadza in Africa, which is very different from the Tukisenta and the Kitavans and other people in the South Pacific, which largely has to do with just lack of availability of plant foods, because most of the landscape is frozen.

There is individual variability, but there is simply no question that the majority of the ancestral human diet, particularly of our human ancestors that were closer to the equator, where we’re thought to originate in Africa, eat diets that are predominated by carbohydrates.

Alex: This is a tangital point, but what you just mentioned, how there’s variation, there’s no one human diet. We are incredibly adaptive creatures, we’re opportunistic eaters, and people were able to survive and thrive on those diversity of diets, just depending on what was available.

Ari: Yes, it’s an amazing thing that human populations can survive on the Tukisenta. People in Papua New Guinea are eating 95% roots and tubers, like those things analogous to sweet potatoes. On the other hand, you have the Inuit in the Arctic on whale blubber and fish and maybe an occasional berry or two. Extreme low-carb diets, mostly devoid of plant foods. Humans can survive and thrive in any number of circumstances on any number of diets is a pretty remarkable phenomenon.

Alex: The final point I’ll say with regard to that, too, is people get tripped up when they think that meat was important for evolution, therefore we are meat eaters. I just want to emphasize that, we started as herbivores, and after we invented fire, really, we started cooking tubers that made their energy much more available. If you’ve ever compared a raw potato to a cooked potato, one’s basically all fiber, right? The other is all digestible carb.

Then we started eating meat, cooking the meat, which makes it more digestible, eating it. Meat played a central role in our evolution, yet letting us have smaller guts, bigger brains. We were definitely avid hunters. Meat was definitely a preferred food source because it was so energy and nutrient dense, it just made sense from a survival standpoint. None of that means that we did not also regularly consume carbohydrates in the diet. Just want to emphasize that.

How the majority of the population view insulin resistance

Ari: That’s a good point. Let’s circle back, just can you crystallize this idea of how most people view insulin resistance, and then we’ll move on to the new paradigm.

Alex: People say, “Hey, you’re insulin resistant. You have high blood glucose. Let’s increase your insulin sensitivity or do other things that lower your blood glucose.” We’re not going to make any structural changes. What we’re going to do is either give you a drug that increases insulin receptor expression, or we’re going to change your diet to where, “Hey, if you’re not eating carbs, then your blood glucose is normal.” That’s great. Those are, I would say, the two most common paradigms.

Ari: It seems to be a way of conceptualizing insulin resistance that sees it as a biochemistry problem with a biochemistry or pharmaceutical solution or chemical solution, if it’s a natural chemical.

Alex: Yes. Even the dietary change can be thought of as a biochemical change because their focus is on blood glucose. It’s on that biochemical marker and by manipulating the diet, they’re specifically trying to manipulate your blood glucose levels.

Ari: With that said, and I know you’ve actually already alluded to the new paradigm a number of times, but let me have you introduce this new way of thinking about the root cause of insulin resistance.

Alex: Your cells are not structurally robust and because structure dictates function, their function is no longer advantageous to your health. The more that you dig, the more that you realize that the cause of diabetes is fundamentally cellular dysfunction. That can be brought on by several ways that we’ll talk about, but that’s ultimately the crossroads is cellular dysfunction, which is causing these cells to be insulin resistant, which is then driving these biochemical changes in your body because the dysfunctional cells are not acting in the way that they should.

Ari: I want people to get this idea of structure dictating function because I think we are all so trained in this culture, in Western culture, certainly in the US to think of health in biochemical terms, to think of our health as a result of whatever is the list of items that show up on our blood test results at the doctor. We think of health as we are a product of the chemicals, the levels of these chemicals and different compounds floating around in our bloodstream. This idea of structure is a different way of conceptualizing health.

Imagine a bicycle. Imagine having a trapezoid shaped wheel on your bicycle. How well is that bike going to work compared to if it’s a circular wheel? The structure of that wheel, the physical structure at the macro level, not biochemicals, not micro level biochemicals, but the physical macro level structure of what’s happening in that bike profoundly impacts how well it functions. We are so good at understanding something like that, with a bicycle.

I would argue we are so bad about applying the same logic and the same common sense to ourselves, as humans, when it comes to understanding our own health, to understanding the link between physical structure of our bodies and our function, and ultimately our health and disease outcomes. Go in more detail about this, what you mean by structure, what is under the banner, the umbrella of this idea of the physical structure of our body, and then segue into how that is affecting the function of systems that relate to insulin resistance and metabolic health.

Alex: A really easy example of this to think about further, just to emphasize the structure component is I’m going to give two examples here. First, with your muscle tissue, because I think this is really easy for people to visualize. What happens if you have very small, weak, frail muscles? Their physical structure of your muscle is not very good, and the outcome of that is you’re weak, you’re at an increased risk of falls, you’re at an increased risk of injury from those falls, a hip fracture or many other things that are the leading causes of death and disability among elderly adults because this physical breakdown of their muscle tissue, they’re who are primarily affected by it.

Just as a meta example of that, you solve that by doing resistance training and eating food to support the growth of new muscle tissue. It’s literally, hey, our muscles are weak. They’ll look at your biochemistry and be like, “Oh, well, let’s see how much creatine are they responding? What’s your blood urea like?” It’s like, no, none of that is relevant. The issue is a weak muscle. Let’s build the physical structure. Let’s make it stronger. Guess what a side effect of this is? Your muscle tissues are responsible for 80% of glucose disposal after eating.

Ari: Hold on one second. Before you go there, I just want to add one thing to this point of muscles.

Alex: Yes.

Ari: We can visually look at someone and based on how they appear to us, like using our eyes, observing the macro levels, physical structure of their body, we can very easily and probably pretty darn accurately, not probably, pretty darn accurately, guess their physical function of their strength level of those muscles based on looking at the physical structure of them. If somebody has got big, strong looking muscles, we go, “Oh, that person’s probably really strong.”

If they’re physically very frail and they have very skinny, flaccid muscles, you’re going to look at them and think, “No, that person’s probably not very strong.” This is very obvious. This is very common sense. Importantly, I want people to understand if you went and did blood tests of those two individuals, the one who visually you said that’s a strong person and visually said that’s a person who’s pretty weak and frail. If you did blood tests and what you looked at was a 10-page report of hundreds of different biomarkers in each of those people, but you didn’t get to see them visually, you didn’t get to actually look at their physical structure.

All you had was what most people would think of as a much more cutting edge, much more scientifically sophisticated thing, which is this 10-page report of hundreds of things going on in their biochemistry. There is no analysis that you could do of all of that biochemistry marker, no matter how sophisticated, you could add microbiome tests, gene tests, you could add all the tests you want.

You still will not be able to, by any of that data, have come anywhere close to as accurately predicting how strong or weak a person’s physical muscles are as you would have by just a five-second observation or a one-second observation of a person’s physical structure. I want people to get just how predictive simple observations of macro level physical structure are and that this is not only not less scientific or less sophisticated or cutting edge than a biochemistry analysis would be. In many cases, it is actually far more accurate of a predictor of a person’s physiological function than any analysis and any comprehensiveness of biochemistry tests.

Alex: Yes, and I want to add to that too. Biochemistry is just a snapshot in time. What gets overlooked is the future risk of something happening. In your example, the two people could metabolically be equal at that point in time. One year from then, the person who is very weak with low muscle tissue is much more likely to have developed metabolic problems from that low muscle tissue because a breakdown in physical structure has a cascading effect. The more time you spend on that road, the worse it gets. You can’t just look at one snapshot in time and think it’s going to stay that way. That’s the problem. People think it’s static and it’s not. Remember, your body is always adapting to what it has to work with.

The role of skeletal muscles on metabolic health

Ari: Thank you for letting me interrupt you. You were about to segue from the physical muscles example to actually then talking about tying in physical muscles, tying in one’s muscles to the story of insulin resistance and metabolic health.

Alex: Yes, so your muscles are responsible for 80% of glucose disposal after eating. The bigger and more in use your muscles are, so the more that you use your muscles for even light movement, but also lifting things, going for runs, whatever, those muscles are going to rely on stored glycogen within them as a very quick energy source to power all of those contractions. What that’s going to do is that’s going to free up a lot of room within those muscles to store more glucose because your body is going to say, “We’re constantly going through this glycogen. We want to increase our storage capacity of it.”

Now, whenever you eat carbohydrates, your cells are going to say, “Give me those carbs.” They’re going to push glucose transporters to the cell surface, the same transporters that are normally put there in response to insulin, but they’re going to do it voluntarily. They’re going to suck up glucose without you actually even needing to have an insulin response to eating because they want that. They are adaptive. They say, “We want the carbs and we’re going to store it in your muscles for later use.” That’s great metabolic health.

Your body doesn’t even need a big insulin response. It doesn’t need a hormonal signal because your muscle tissue itself is just ready for the glucose. To add to this too, I want to emphasize that insulin doesn’t increase before you eat. What happens is, when your blood glucose levels rise, some of that glucose, it’s a very low threshold, it just passively moves into the pancreas, produces energy, and that energy production in the pancreas is what stimulates the pancreas to then secrete insulin. The insulin is a response to the glucose.

If your muscles are all saying, “Give me glucose,” as soon as that glucose hits your blood, then your liver and your muscle tissues are going to suck it up before you have enough of it to get into your pancreas. Instead of having a huge insulin response, your pancreas is going to think, maybe you only had a few grams of carbohydrates when, in reality, you had a full meal, because the rest of your tissues were eager to suck it up before your pancreas ever got a chance.

Ari: Yes. [crosstalk] Sorry. Go ahead.

Alex: I was just going to say, and that’s exactly what you want to happen. That is your body working efficiently and that’s your body working as it should. It is a result of building big, strong muscles that you constantly use. The exact opposite happens when you’re weak and you’re frail. Your muscles, you’re never using them, so they don’t have any more room to store glycogen because you’re never burning through it. Because your muscles are so tiny, you simply can’t store as much glycogen as you could if you had bigger muscles. It’s a direct result of what’s going on with the physical structure of your muscle.

Ari: There’s a subtle thing that happened there, which was using big, strong muscles as an example of the link between structure and function in terms of just presenting this as an analogy, as a way of understanding the structure-function link like, hey, look at somebody. There’s big, strong muscles, and you can reasonably assume there’s strength. This person is a strong person that can move heavy objects.

Then you subtly actually transitioned into big, strong muscles as the structure in terms of the physiological role that they play in insulin resistance. Not just in terms of the function of lifting heavy objects, but the function in terms of metabolic health and soaking up glycogen, acting as a glycogen sink. Just wanted to make sure listeners caught that. That was a nice little subtle flow of concepts.

What you just explained is the role of physical structure of muscles in insulin resistance and metabolic health, why muscles are more than just a thing about vanity but actually play a central role in our metabolic health.

How fat tissue works in the body

Having said that, there is one other layer of the story of body composition and physical structure that is an even more important player in the story of insulin resistance. Take people through that.

Alex: That one would be your fat tissue. Again, this is actually something you can, for the most part, look at and visualize on someone. Your body fat, if it’s working properly, it should store energy pretty readily and then give it up pretty readily as needed. It will respond to the signals your body puts out and it will say, “Hey, they ate an extra big meal this time. Muscles got their fill. They’re happy. We have some leftover. We’re going to put it in fat tissue and store it for later because having that energy in the bloodstream is harmful because it’s going to interact with a bunch of things it shouldn’t. Let’s safely store it away and then they’re probably not going to eat for a bit and so we’ll start to pull on that energy and use it to sustain ourselves until they eat again.” Now, if a fat cell isn’t working properly, if it has a physical breakdown of its structure, then you are not going to be able to store that excess energy, not easily anyway. This directly causes type 2 diabetes. Also, I would just emphasize it’s going to cause metabolic problems directly. There’s a really good example of this. It’s a disease. It’s called lipodystrophy. This is a disease where fat cells basically just don’t work. It can affect just isolated parts of the body or it can affect the entire body but it’s a disease where your fat cells cannot store energy. They have a genetic defect that led to structural problems that make them incapable of storing excess energy.

These people have substantial levels of insulin resistance by definition because their cells just don’t store the energy and they have type 2 diabetes and a host of metabolic problems because any excess energy in their blood has nowhere to go. These people need to work around their condition by doing two things. They need to constantly be moving to free up as much space as possible in muscle tissue to take care of excess energy. They need to eat very small frequent meals because they cannot have too much energy in their blood at any given time or else it will hurt them. Now, the same thing happened is the most common cause of type 2 diabetes but for a different reason.

Ari: The most common cause of insulin resistance, more [unintelligible 01:02:59], right?

Alex: Yes, exactly, but the reason’s different. It’s not due to some genetic defect. It’s because their fat cells have stored so much energy that the cell says, “Hey, I can’t put more energy inside me, so I’m going to shut myself off from insulin signal, because if I did put more energy inside me, it would risk causing damage to me as a cell.” [crosstalk] Well, think of a balloon. You can’t blow infinite amounts of air into a balloon. At some point, it would pop. The physical structure would give out. It’s the exact same with fat cells.

Your fat cells can only store so much fat, and there is a genetic component to how much fat an individual can store. Some people have a lot of fat cells and they have an ability where, when their fat cells get too big, those fat cells start to release signaling molecules that lead to the creation of new fat cells. As long as this process continues to occur, these people can actually become morbidly obese and not have any biochemical signs of metabolic dysfunction.

Can you be overweight and metabolically healthy at the same time?

Ari: This gets into the controversial territory of the obese but metabolically healthy category, the idea that some people have put forth that it’s possible to be extremely overweight and yet still metabolically healthy.

Alex: Yes. Technically, they’re right but two points I want to raise is, the first is that research looking at these people shows that, even though they’re metabolically healthy at a point in time, they’re at a 50% to 80% greater risk of developing metabolic problems within five years of them being metabolically healthy. That’s simply because, even though their bodies are just amazing at storing fat and doing that, the process is limited. It’s going to give out at some point. The second point I want to raise is, even if you’re metabolically healthy, you’re still going to have massive joint degeneration. Your physical structure of your skeleton is not used to carrying all that weight, so you’re going to have a physical breakdown in other ways that aren’t related to what’s going on in your bloodstream. You can ask anyone, hey, why don’t you wear a 100-pound weight vest for the entire day and then the next day take it off and let me know how your back feels, let me know how your knees feel? Carrying that excess weight, it’s not healthy from a physical structure standpoint.

Anyway, the reason that this fat cell dysfunction is the primary cause of insulin resistance for most people which ultimately leads to type 2 diabetes is because they have too much body fat and they have reached their capacity to store more body fat, so all of their fat cells have basically said, “We’re going to protect ourselves, so we’re going to turn away any further energy.” Now, the body doesn’t like this. It’s almost like there’s two minds to the body. On the one hand, you have cells that are looking after themselves.

On the other hand, you have cells that are also looking after the body in general. Your fat cells are saying, “Hey, I can’t do anymore it’s going to hurt me.” Now, you still have a bunch of energy, a bunch of glucose in your blood, and your pancreas is going to say, “Wow, all this glucose, I better pump out more insulin because that’s my job.” Now, you have more insulin in your bloodstream which is going to override these safety mechanisms of these fat cells. It’s going to try and force more energy into them. This is the very first step in not insulin resistance but into metabolic dysfunction because this is now what causes these fat cells to become dysfunctional.

What happens at this stage is these fat cells they’re now considered lipid-overloaded so they have too much fat in them. This stimulates an immune response against the fat cells, so now your immune system is saying, “Hold on, this fat cell is dysfunctional. This is a danger to the body. I need to start attacking it.” You have a lot of this localized inflammation in the fat cells that then spreads throughout the body. This is how low-grade inflammation starts. It starts in your fat cells and then all of these immune signaling molecules that cause inflammation because inflammation is just an active immune system. That’s all it means. I spread throughout the body so that you can recruit more immune cells to the area.

These fat cells that are now so lipid-overloaded that insulin no longer even has an effect on them, I start secreting their fat back into circulation because they’re damaged, they’re dysfunctional, they’re being attacked by immune cells insulin which is not just responsible for storing glucose but for locking away energy to keep it out of the bloodstream is no longer transmitting its signal. Now, you have a leakage of fat back into the bloodstream.

This is why people with obesity and type 2 diabetes from a biochemical standpoint, they have greatly elevated levels of fatty acids in their blood. It’s because it’s leaking back into circulation. Now, people get really focused on glucose. They think, “Hey, high glucose is bad. It causes glycation. We got to keep that in control.” High fat in your blood is equally as detrimental.

Just do a quick Google search for lipotoxicity. Having a bunch of fatty acids in your blood can cause damage to tissues, so your body says, “Whoa, we can’t let this happen but we can’t put this energy, these fats back into your body fat because those cells don’t work anymore, but we need to get out of the blood. What we’re going to do is we’re going to start putting it in places where it shouldn’t go.” This is what leads to the development of visceral fat. This is the fat that surrounds all of your organs. That fat, ideally, would be as minimal as possible. When you have too much energy in your blood from your fat cell dysfunction, your body says, “We need to get this out of the bloodstream. We’re going to put it in the liver. We’re going to put it in the pancreas. In fact, we’re even going to shove some of it into muscle tissue, which is then going to affect the physical function of the muscle tissue, reduce its insulin sensitivity.” It’s a whole cascading effect.

Then in the liver, the buildup of fat in the liver causes the liver to become unresponsive to insulin, causes the liver to start secreting glucose uncontrollably, which elevates your fasting glucose level. The fat in the pancreas begins to interfere with its ability to create and secrete insulin. Over time, your pancreatic ability to create insulin actually goes down. This is what happens when people say that they’re insulin-dependent diabetes. It’s because they have been in this state of physical structure breakdown for so long that it has now damaged their organs and their pancreas now more resembles someone with type 1 diabetes because its physical structure was destroyed by this cascade of events that ultimately started in their body fat.

That sequence of events that I just described, you overdo your energy storage capacity, your fat cells become dysfunctional. They become inflammatory. Fat gets secreted into your bloodstream. It gets stored in your organ tissues. Those organs no longer function and suddenly, your blood fat and your blood glucose levels all rise. You’re diagnosed with type 2 diabetes, and you’re given some metformin thinking that that’s going to solve the problem. No, it’s fundamentally a structural breakdown. I’m sure that you have a lot you want to say, Ari, but before that, the last thing I want to say is, and this has been demonstrated now multiple times in the scientific literature, the solution to literally reversing diabetes to where you can actually eat carbohydrates without any problems–

Ari: Alex, hold on.

Alex: Yes, all right.

Ari: I’ll interrupt you right there for maximal suspense before you deliver the solution [laughs].

Alex: Okay.

The link between excess visceral fat and diabetes

Ari: Before you get there, let me ask you this. There are some people listening to this, maybe their eyes are glazing over and they’re saying, oh my god, this is so much detail with all these mechanisms. Why don’t you just tell me what to do? Why does any of this actually matter? Why does it matter whether you conceptualize it as a biochemical problem with a biochemical solution, or you conceptualize it this other way as a structural problem? Why does any of this matter at all?

The reason that it matters how you conceptualize it is because the way you conceptualize the problem is going to be the biggest determinant of how you conceptualize the solution to the problem. With that said, Alex, now I want you to go into what you were about to say which is, now that we understand this through a structural lens, through the lens of physical structure dictating function and physiology, how does this new paradigm, this new understanding of insulin resistance lead us to a different way of conceptualizing the solutions to this problem?

Alex: If you trace it all the way back to the ultimate cause, well, you can trace it back to two parts. The diabetes starts because of excess fat in the liver and pancreas, but the excess fat gets in your liver and pancreas because you have too much fat on your body, so the subcutaneous fat that’s beneath your skin. In both cases, the solution is fat loss. If you lose body fat, if you’re going to burn up the fat that is stored on your body, then you burn through the fat that’s in your organ tissues. You use that for energy, so it’s not there anymore. You free up space in the fat cells beneath your skin so that they can now start to safely store and release energy properly again.

The most common cause of excess body fat

Ari: Okay, there is one intermediary linking those things that you just described here that I want to make sure we explain. One could make the case reasonably, I think I would make this case, as much as I like this way of conceptualizing the real causes “of insulin resistance”, I think we could make the case that what if we just keep going more upstream of even this. We say, you were just tracking something upstream of this fat cell dysfunction and the insulin resistance is the accumulation of fat in the liver and visceral adipose tissue. What causes that? Well, upstream of that is too much fat in the subcutaneous fat stores. Now, we need to ask, well, what causes that? What are the root causes of why we are accumulating too much subcutaneous fat stores? I want you to answer this by also stating the context that this problem is a modern human problem that doesn’t exist in all those hunter-gatherer tribes that we were discussing before. If we’re talking about real root causes, we need to understand the root causes of the structural dysfunction too and why that is only present uniquely in modern humans living the modern Western lifestyle as opposed to our hunter-gatherer ancestors, the hunter-gatherer tribes who still exist today, who have been studied by researchers?

Alex: I’ll go two more upstream causes. The cause of overfilled fat cells is simply that you’re eating more energy than your body is able to use up chronically over time. The reason why you’re eating too much, I would argue, and I think, Ari, you would agree, is that the modern Western diet is just a potpourri of hyper-palatable, super calorie-dense, completely unnatural foods that are literally engineered by people whose entire jobs is to make them taste good to make us eat as much as possible. This problem doesn’t exist in any indigenous tribes because, one, they have to work for their diet, and two, their diet is composed exclusively of natural foods that we evolved eating, that our bodies are adapted to using.

Ari: By the way, quick side note, this also loops back into our previous discussion around natural versus man-made stuff and the potential for adverse effects between those two being considerably different. That’s a quick side note.

Alex: Yes. On that too, not every processed food is bad and harmful. You really have to approach it with some common sense. You could find a nice jar of spirulina powder that’s ultra-processed but–

Ari: Or whey protein or collagen [unintelligible 01:18:35]

Alex: Yes. Those are all, I would argue, very healthy things to include in the diet. We’re talking about the foods that I think would come to mind for everyone just when they hear the word ultra-processed junk food. This is the stuff that lines the supermarket shelves, the stuff that is rich in fats, processed, heavily processed and refined carbohydrates, salt, flavorings, everything that makes us want to eat it and literally, tricks our biology into consuming more of it. Because from an evolutionary standpoint, all of these aspects of the food are what our biology is tuned towards for survival. When you’re trying to survive out in the jungle or on the savannah, you want to eat calorie-dense foods that are rich in carbohydrates like sugar. Honey is a big one around equatorial tribes. They love honey. They will gorge on honey when they find it.

Ari: [unintelligible 01:19:49] It’s also true in my personal household. I have two little children that also gorge on honey. I’m not going to lie, I may also do that from time to time.

Alex: Yes, it’s an ingrained survival mechanism. The gorging thing is actually a great pivot point too, because overeating is not inherently bad. Our bodies are designed to deal with periods of overeating and they’re designed to deal with periods of not eating at all. People don’t get unhealthy because maybe they binge over a weekend every now and then. People get unhealthy because they regularly consume really, really crappy foods that cause them to unconsciously overeat over a span of weeks, months, years, decades.

Ari: I want to add one thing. Again, context along with hunter-gatherers, our human ancestors, are, you could say, our natural living counterparts. If we look even more broadly to other animal species, none of these other animal species that we might observe, whether it’s a zebra, a deer, a tiger, whatever, a squirrel, or a raccoon, or anything like that, none of these species have obesity epidemics. You don’t see them walking around with huge amounts of fat stores, unless maybe they’re preparing for hibernation, which is also an intelligent thing in hibernating animals. They’re not starving to death, assuming they’re in an environment that has food available to them. They know how to regulate their level of body fat within a healthy range.

It turns out, and humans do too in a proper human environment like the one that we evolved in. All hunter-gatherer tribes, when we look at them, they know how to regulate their body fat stores in a healthy way. This is not a conscious thing. It’s not that they went and read diet books and learned about calories and that they go into their apps on their phones and count their calories every day and track their calorie expenditure. This is all done as a natural non-conscious product of bioregulatory processes.

We have a body fat set point system that has been designed into us over millions of years. Prior to even the species of Homo sapiens, this system evolved. This system involves a feedback loop between a certain area of the brain and the hypothalamus that is involved in– well, this is called the body fat set point regulatory system. It is in sync with our body fat stores which produce a hormone called leptin. That’s the primary thing that is involved in this regulation.

The more body fat stores you have, the more leptin that’s in your circulation that feeds back into the system in the brain, which is designed to sense, okay, do I have lots of energy in storage on my body or do I have very little? Do we need to, if I have very little, then I need to go out and seek out food and find food to store more energy in my body fat stores to make sure I have it available in case I’ve got to go without food for a period of time? If I do have lots of leptin in circulation indicating sufficient body fat stores, then I don’t need to feel so motivated to go pursue more food. That’s how the system is designed to regulate.

The problem is the modern environment and the modern diet, as Alex explained, of hyper-palatable food that has been literally engineered for us to find pleasurable, takes us out of what’s called homeostatic eating, which is this body fat regulatory system operating correctly as it does in pretty much all animal species, where you eat food, you feel non-consciously motivated to eat an amount of food that is roughly in proportion to how much energy you’re burning and in need of on a daily basis or on a weekly basis.

You’re consuming the amount that is essentially equivalent to how much you’re burning off, so your body weight and body fat levels stay stable over time. That’s homeostatic eating in homeostasis with what your body actually needs. The modern environment and diet pulls us out of homeostatic eating into what’s called hedonic eating, eating more for pleasure because, again, we have literally foods that are designed to be pleasurable by PhD food engineers. It succeeds, especially over time, in overriding our body fat regulatory system and causing us to eat more and more hedonically and not homeostatically, and to the point where many people literally over years and decades quite literally forget they’re totally out of tune with the homeostatic signals. They don’t even know how to regulate homeostatic eating anymore. I’ve seen people, when they’re losing weight after they’ve become obese over several decades and then they’re trying to lose weight. I’ve seen people who, in that state, they start to feel a sensation in their belly that their belly is burning and they’re questioning whether they should go to the hospital or not because they think they’re afraid something’s wrong. Then you have to explain to them, no, that’s what hunger feels like. That’s what actual physiological hunger feels like, not hedonic hunger, like I desire food because I’m excited to eat that, because I know how good it tastes and how much pleasure it gives me.

Homeostatic, real physiological hunger is like, oh my gosh, my body actually, my stomach’s burning because I actually need fuel because I’m running so low on fuel stores. There are many people in our society who haven’t felt that sensation in decades, maybe since they were a kid. This is how the modern environment overrides this body fat set point system that’s been designed into us and pulls us out of homeostatic eating. The one last point that I want to make here is we have a paradigm of health of medicine that, as we’ve said, conceptualizes problems through a biochemistry lens, and it has the illusion of being scientifically sophisticated.

If someone is presenting you a paradigm of insulin resistance and diabetes where they say, well, here’s the biochemistry of the GLUT4 insulin receptor and there’s this mechanism and that mechanism and this biochemical and the AMPK and insulin levels are this and hemoglobin A1C is this and look at all your blood markers and look at this marker and that marker and let’s do gene testing to see which gene variants are associated with insulin resistance and let’s do microbiome testing to see which microbiome profile is associated with insulin resistance and genes and blah blah blah and this biochemical and that biochemical, it can seem enormously cutting-edge and scientifically sophisticated.

If someone is presenting that paradigm to you where they’re presenting those things as the causes of insulin resistance, “the causes”, and they’re not presenting what Alex just explained about all these things that are upstream of that with regards to the physical structural dysfunction and then what are the root causes of that physical structural dysfunction, which are the modern diet and the modern way of life and the modern environment, and if they don’t have that context of understanding those things as the root causes, it reminds me of the quote, “If you can’t dazzle them with brilliance, baffle them with bullshit.” You can present this way of understanding this problem that sounds to the uneducated persons enormously scientifically sophisticated, but it’s actually a bunch of BS if it isn’t grounded in the context that you just presented.

The most common recommendation to lower your blood pressure

Alex: Yes. Two things that I wanted to add to that too to drive this point home is this physical structure issue doesn’t just apply to insulin resistance, but it applies to almost everything. One simple example of that is, if you think about cardiovascular problems and high blood pressure, most of those problems, a common recommendation is you need to start exercising.

Exercise is great for lowering blood pressure. It reduces your cardiovascular risk. Why? Why does it do that? Exercise doesn’t have those benefits because it’s changing your biochemistry. It has those benefits because when you do aerobic training, your heart physically becomes stronger. Your blood vessels physically become better able to dilate and contract as needed. Your cardiovascular system literally becomes physically stronger. It’s not a biochemical issue. I think for most things you can make that argument.

Ari: [unintelligible 01:30:26] we do. [chuckles] [unintelligible 01:30:28] for the last year.

Alex: Yes, exactly. We are constantly exposed to toxicants in our environment and they cause all sorts of problems. They cause the physical degeneration of many cells and tissues and they’re harmful. How do you become better able at dealing with them? You build up the physical structure, the physical capacity of your liver so that your liver is better able to take in all of these toxicants from your blood, neutralize them, and get rid of them. There is ways to do that. If you have strong organ systems, you’re going to be healthy. That’s fundamentally the truism of our existence. People are so focused for their health and longevity on making sure that all of their biomarkers are perfect which, cool, but you’re completely overlooking all of the macro-level forces that ultimately determine most of those biochemical markers.

Ari: Yes. Well said. Go ahead.

A note on the MTHFR mutation

Alex: The second point I wanted to bring up too is that Ari and I are not saying that biochemical markers are not important. We’re just saying that we don’t think they should be the central focus and they shouldn’t be the primary reason for decisions on what you should do to improve your health. If you have elevated LDL cholesterol, you could look at that and be like, “Well, I’m going to take a statin that’s going to lower it.” Directly addresses the biochemistry. Or you could figure out why is it elevated, is it related to your diet, what’s going on with your liver that’s preventing it from expressing LDL receptors that take up the LDL molecules?

You can try and find a way that is more holistic, I would call it, instead of trying to short-circuit systems in your body that are going to lead to adverse effects. Like, in the case of statins, you have myopathies and you have diabetes as another potential outcome. In some situations, biochemistry is actually pretty important. One example I would use for that is the MTHFR mutation.

The reality is that this mutation, and I did a whole podcast years and years ago with Chris Masterjohn on this, but the MTHFR mutation, the whole reason that it actually spread and became so prevalent in the human population is because the primary mutation works by reducing the binding affinity of that enzyme to riboflavin, which it needs to work. The human diet was so rich in riboflavin historically that this mutation didn’t matter. It didn’t impact our health.

Now, modern humans eating their crappy modern human diet are in a position where this mutation does matter. You can actually circumvent the issues with the MTHFR enzyme by simply supplementing more riboflavin to mimic what we would’ve naturally gotten in our diets way back when. Biochemistry can be helpful to figure out if you do have unique causes that might be taking away from your longevity and your health span because there’s always going to be those weird little things that could pop up, but it’s not the biggest needle mover. The biggest needle mover is your physical body and how much you’re taking care of it.

How to solve insulin resistance

Ari: Well said. Again, looping back to this insulin resistance, this way of understanding it and understanding the upstream causes of it, now with that in mind, we can understand why the solution to this problem is not simply taking a drug or a natural chemical, to your point earlier, or injecting insulin because even if you normalize blood sugar measurements based on that, you have, to a large extent, not solved the fundamental problem, the fundamental root cause that is driving this metabolic dysfunction. Unless you have solved the structural problem that is present, you have not solved the problem. How do you solve that structural problem?

Alex: Ideally, you would start eating a whole foods-based diet with low reward value. That would just make this whole process of eating less easier and let your natural homeostatic processes come into play. Talking about that could probably be an entire podcast on its own. Because everyone is different, what I would say is, basically, just ditch as much of the processed crap that you can. A ketogenic diet is really good for this because if you’re not eating carbs, that eliminates pretty much all processed junk.

Ari: Except for all the [chuckles] ketogenic processed foods that have come to the market with the rise of the popularity of the keto diet.

Alex: Oh God, yes, I know.

Ari: You have to feed that. The fat bombs and all of that.

Alex: Yes.

Ari: Yes, the keto processed food.

Alex: Yes. Fat bombs are not better than candy just because they’re full of fat. Eating a whole foods diet, whatever that looks like, I’ll leave it up to you. Fundamentally, you want to find a way to sustainably just start losing fat mass. [crosstalk] Roy Taylor–

Ari: Yes. Sorry, go ahead.

Alex: I was going to say Roy Taylor showed this really well. Although he did it rather extreme because, in research studies, time’s limited. He showed over several studies now both in people with obesity and most recently, normal-weight people, people with normal BMIs who had type 2 diabetes, that if you make them lose about 15% of their starting body weight, it will reverse diabetes to the point where they’re on zero medications and they’re now eating a weight-maintenance diet that has carbohydrates in it, and the diabetes is gone. Their body is able to regulate that glucose again.

Ari: Yes, this is the key point [crosstalk] that I wanted to make sure that you emphasize to people, we’ve been searching for the biochemical cure, the pharmaceutical cure to diabetes when there is actually a real cure for diabetes that has already been shown in research to essentially reverse full-blown diabetes sometimes in a matter of a few weeks. By doing what? Correcting the physical structure. How do you do that?

Alex: Yes, exactly.

Ari: Through body fat loss, through losing fat so that the fat cells can work properly because structure dictates function. If they’re not constantly being inflated to their maximal capacity like an inflated balloon that’s about to pop, if you allow them to deflate and get rid of some of those stored fatty acids, now the physical structure of that adipose tissue organ can work correctly. All of a sudden, your metabolic health, your blood sugar starts to function properly again. Just literally some of these studies from Roy Taylor and others have shown that, in 6 weeks or 8 weeks or 12 weeks, you can take people who have full-blown diabetes, who have been on medication for a decade or more, and completely make them non-diabetic through fat loss.

Alex: Yes. Here is the one caveat to that, and this is important to mention, is one of the things he found in his studies is, among people who had diabetes for a very long time, some of them could not actually restore normal metabolic health after they lost fat mass. The reason for that was because they had diabetes for so long that the physical structure of their pancreas deteriorated, so now they were in an intermediate state in between type 2 and type 1 diabetes. Even though the rest of their body was working fine, their pancreas is now no longer able to produce enough insulin to properly regulate blood glucose.

Preliminary findings on ways to restore the pancreas

Ari: The distinction being that this is, [crosstalk] at that point, less a problem of fat cell dysfunction and more a problem of simply destruction of the pancreas.

Alex: Yes. We don’t currently have any cures for that, although I will say there is some preliminary human and animal data suggesting that time-restricted feeding and intermittent fasting allows pancreatic beta cells to regenerate. I want to emphasize preliminary, but in my opinion, if you’re somebody who has pancreatic damage from having diabetes for a long time or if you’re somebody who has a genetic defect in their pancreatic beta cells to where, from birth, you had problems with your insulin secretion abilities, intermittent fasting and a lower carbohydrate diet are probably wise. Just because until you’re able to actually fix those structural defects of the pancreas, it doesn’t really matter what else you do. You need to do something to make sure that you’re not getting excess energy in your blood.

The Fat Loss Blueprint

Ari: Yes. Alex, this is the point in the discussion where, after we’ve outlined this new paradigm, this new way of understanding insulin resistance and diabetes, we’ve presented it through this physical structural lens and how structure dictates function and then talked about what’s upstream of these structural problems. The solution being predominantly body composition now opens up 10 hours more of new discussion about how to optimize your body composition. You’ve touched briefly on what is the most important single strategy to lose fat and for general health, which is to eat an unprocessed whole foods diet. That is the number one strategy.

Going beyond that, there’s, obviously, as I said, many hours of discussion of the nuances of optimizing body composition. Just talking about muscle gain and muscle strength by itself is many hours of discussion. Just talking about fat loss, potentially many hours of discussion. We know it’s many hours of discussion because we literally created a course called The Fat Loss Blueprint that has many hours of discussion on fat loss. Many hours of actual scientific lectures taking people through the science of understanding, first of all, what causes fat gain, how we get fat in the first place and most importantly, how do we fix that problem?

Presents a selection of advanced fat loss strategies that, as I said at the beginning of this, is essentially a compilation of everything that we know, the best of the best information and the most effective advanced fat loss strategies beyond the basics that everybody knows of, eat a whole foods diet and do exercise. “Okay, fine. I’m already doing that, but I still can’t lose all the weight I want.” This is for those people. This is not a basic thing of teaching you the basics that everybody already knows.

Again, this is advanced fat loss strategies and again, it’s free of all the bullshit and all the gimmicks that you commonly see in the realm of fat loss online with all these charlatans and all of this pseudoscience and all of these gimmicky extreme diets and everybody trying to be the one diet guru who creates the latest diet that goes viral, that everybody wants to jump on, that gets them on Dr. Oz and all the shows that they can talk about why their wacky diet is the one true ancestral diet and creates these magical fat loss effects.

There’s this whole culture of pseudoscience and BS that exists in this realm. I really want to distinguish what Alex and I have created. This is no BS, no gimmicks, no extreme diets, no hypey promises, and all that kind of stuff. This is for people who are quite frankly, intelligent enough to see through all of that BS and who actually want something that’s evidence-based, that’s rock-solid, grounded in science, they want to learn the actual science of fat loss and be presented with a selection of advanced fat loss strategies that we know from the actual literature. We’re going to show you the studies to back it up this stuff actually works to support not just rapid fat loss but even more importantly than that, lasting sustainable fat loss and be supportive of good health. We need to not just lose. Any monkey can lose fat rapidly and just starve yourself. There’s lots of ways of doing extreme diets that can cause 20 pounds of fat loss in four weeks or six weeks or eight weeks, but what we really care about is lasting sustainable fat loss and changing our body fat set point, changing the set point that our set point system wants to regulate our new body fat set point at. How do we work with our biology to do that? That’s what this program is all about.

For everybody listening, I hope you enjoyed this podcast with Alex. I would strongly encourage you to check out our Fat Loss Blueprint program. If you’re watching this on YouTube, there’ll be a link down below in the comments, or you can go to and click on programs and then click on The Fat Loss Blueprint as I said. Right now for the next seven days, we’re offering $200 off the normal price, so you can get it at $297 instead of $497.

With that said, if you’re interested in losing fat, there is, in my opinion and in Alex’s opinion, no better resource for losing fat sustainably and effectively than The Fat Loss Blueprint that we’ve created. I hope that you will check it out. Of course, there’s a 30-day money-back guarantee, so you’re free to buy it, check it out, try it out for 30 days if you’re not blown away by the information. Just email us and ask for a refund, no problem.

If you say, “Hey, I already knew all this stuff. I’ve been reading about fat loss for 10 years. I knew all this information and I didn’t learn anything new here,” fine. Well, we’re happy to give you a refund. Unless you’re a world-class expert in this field, I really, really doubt you’re not going to learn a whole bunch of new stuff that is really going to blow your mind and more importantly, change your body composition, help you lose fat sustainably for life and help add years to your life and energy to your life. I hope you’ll check that out if you’re looking to lose fat. Alex, thank you so much for coming on the show yet again.

Alex: Yes.

Ari: To everybody listening, if you guys want Alex on again, we can do more of a deep dive on some of the advanced fat loss strategies. Maybe I’ll have him on as a solo episode as well where he can just present information from studies. Who knows? We could do a live Q&A. There’s a lot of different ways we could do this. If you guys want to hear more from Alex, let me know down in the comments below or send us an email at support at Alex, thank you again. To everybody listening, I will see you again soon.

Show Notes

00:00 – Intro
00:45 – Guest Intro
05:01 – Metabolic health – an overview
11:05 – The potential effects of Diabetes 2 on long term health
23:58 – The conventional view on insulin resistance
31:51 – Are herbal supplements better than pharmaceutical drugs?
38:54 – Carbs have been part of our ancestors diets
44:26 – How the majority of the population view insulin resistance
55:06 – The role of skeletal muscles in metabolic health
1:00:11 – How fat tissue works in the body
1:04:54 – Can you be overweight and metabolically healthy at the same time?
1:13:08 – The link between excess visceral fat and diabetes
1:15:28 – The most common cause of excess body fat
1:29:34 – The most common recommendation to lower your blood pressure
1:32:07 – A note on the MTHFR mutation
1:35:08 – How to solve insulin resistance
1:40:50 – Preliminary findings on ways to restore the pancreas
1:42:03 – The Fat Loss Blueprint

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