 It's this inability to make this shift that we now know is driving almost all of our diseases of aging. This episode is intended only to expand your knowledge and is not a substitute for seeking medical advice. It's important to first communicate with your doctor regarding any of the information you wish to put into practice, especially for serious illnesses. Okay, let's get started. All right, so before we dive into metabolic flexibility, it's important to understand what mitochondria are. For those of you who have read my last few books, including The Energy Paradox and my most recent best seller, Unlocking the Keto Code, mitochondria are those little organelles in almost all the cells in our body that convert the food that we eat whether it's sugar, protein or fat into the energy currency that we burn called ATP, adenosine triphosphate. And without getting too technical, the ability of mitochondria to take these various foods and turn them into ATP actually determines how flexible you are with fuel choices. All right, so normally mitochondria can either take glucose, sugar or fat in the form of what are called free fatty acids and convert them via the electron transport chain. And if you've read the new book, it's the mito club where things are happening, convert these into ATP. And normally, mitochondria can take sugar or fat and convert it into ATP. Now, let's get clear. Quite frankly, mitochondria are really good at converting glucose, sugar, into ATP. They're very efficient at doing this. On the other hand, if you run out of sugar to burn for ATP production, then normally you should be able to instantaneously start using fat to make ATP. Now it's a slightly different mechanism in the mitochondria but the end product is virtually exactly the same. So taking sugar to make ATP, taking fat to make ATP, ought to be a seamless transition when sugar runs out. Unfortunately, as I mentioned in the introduction, the vast majority of people who are overweight or obese no longer can make the transition from burning sugar as a fuel source for ATP to burning fat as a fuel source for ATP. And surprisingly, 50% of normal weight individuals cannot make a conversion between burning sugar and burning fat to make ATP. And you go, well, gee, that sounds kind of important. So why is that important? Well, normally let's suppose you and I have dinner at six o'clock at night and we stop eating and we get no more calories until the next morning. Usually by about eight hours into not eating, most people pretty much run out of sugar to burn as a fuel. So that while you're sleeping towards the end of the night, you pretty much stop having sugar available. You've run out of the sugar that you've eaten and you've run out of glycogen, which is the storage form of sugar that's in our muscles and in our liver. And so what should normally happen is that once we run out of sugar, we would say, okay, no more sugar, we got plenty of fat, we'll just tap our fat stores and we'll start burning fat as sugar for ATP until the next meal arrives. Sounds simple, doesn't it? Well, not so fast. We're designed for feast or famine. That means long ago when we found a buffalo or we found the best fruit tree in the world, we would eat until we couldn't eat anymore and we would meet all of our energy needs, actually very quickly, and whatever was left over that we didn't need to make energy right then, we'd convert all that extra food into fat. We would literally charge our batteries. Now, the reason we're built for famine is guess what? We didn't get a buffalo every day of our lives. We didn't have a fruit tree every day of our lives. And so those times when we didn't have anything deed, it would be a great design that if we ran out of sugar or protein, we have this battery that's charged with fat that we can now draw on to keep our energy production going until the next great meal arrived. And that was our design, feast or famine. And through most of history, that's how our design was. You've heard me say this many, many times, but great apes, and quite frankly, we're a great ape, only gain weight during fruit season. And fruit season doesn't happen 365 days a year in the jungle. It happens in the summer and early fall. So great apes gain weight eating fruit, and then they live on that extra weight when times are rough, lean in the winter and spring until the next fruit season comes. And we actually carry that same ability. And you've heard me talk about before, one of the best ways to gain weight is to eat fruit, more on that later. Okay, so as you've learned about in unlocking the keto code, we can compare our system to a hybrid car. By that I mean if we have gasoline, and let's call gasoline sugar, we'll burn gasoline in our combustion engine. And if we've got gasoline, whatever we don't need to power the car, we'll charge the battery in our hybrid car as we're driving. Then when we run out of gasoline, we switch over to battery power which has been charged by running the engine. Let's call the battery fat. Now, in a hybrid car, you should make that transition seamlessly. You can't really tell when you're on gas and when you're on battery, except the noise of the engine running. But you can switch instantaneously. And you and I are supposed to be a hybrid car so that when we run out of gasoline, the battery that we've charged our fat cells instantly start providing the fuel to make ATP. Well, not so fast. So in comes a hormone that by now every one of us has heard about called insulin. Most people hear about insulin because way back when we thought that diabetics didn't make enough insulin to get blood sugar out of their body, out of their blood. In fact, insulin is a hormone that sells sugar and protein to our muscles. Basically is a salesperson that says, hey, this person had some great sugar, had some great protein, open the door, I wanna sell you this. And insulin opens the door to the cells and lets sugar and protein into the cells, particularly muscle cells. Now it does that normally. But let's suppose our muscle cells are full. You've had plenty to eat and or you really haven't been exercising much so the muscles haven't had to burn a lot of calories. So now when insulin comes knocking and says, hey, open the door, I wanna sell you this. The muscle salt goes, are you kidding? I'm stuffed, couldn't eat another bite. No room for anything in here. I don't wanna buy anything. Well, because of the feast or famine design, insulin then, if the muscles don't want all this stuff, insulin activates a hormone called lipoprotein lipase and I promise there won't be a test at the end of the broadcast. And it ushers sugars and proteins into fat cells. So instead of trying to get it into the muscle cells that clearly don't want it, insulin says, I get it, you'll thank me someday because right now we got plenty to eat, I'm gonna charge the battery, I'm gonna put it into fat cells. So the next time we run out of gas, the next time we run out of food to eat, the battery will be fully charged and you'll be the good big winner when the next famine arrives and that's our design. Makes perfect sense. So when you're eating, particularly when you're eating sugars and proteins, carbohydrates and proteins, you turn on insulin, insulin goes up, tries to make the sale to the muscles don't want it, insulin goes, well, that's okay, I'm gonna store it as fat until you need it. Now here's the problem. Normally when you stop eating, insulin plummets, it goes down. What that does is two things. Number one, it no longer turns on an enzyme to store fat, it just stops making that. But number two, and this is probably the most important thing you're gonna hear all day. Normally if your insulin level is up, you're eating and you're storing fat. If you're trying to store fat, if you're trying to charge the battery, the last thing you would wanna do logically is take food out of storage, take energy out of storage, drain the battery while you're trying to charge it. So not only does insulin put things in the battery, but when insulin is elevated, it blocks fat or energy coming out of the fat source. Because if you're trying to store fat, it would be dumb to pull it out. So insulin when it's elevated stops any fat from getting out of fat cells. And it does so by creating another enzyme or blocking an enzyme called hormone-sensitive lipase. Hormone-sensitive lipase. I wonder what hormone-sensitive lipase is sensitive to? Insulin. So when insulin is elevated, you cannot release fat from fat cells. Okay, now getting back to how we started all this. Remember I told you that 88% of overweight people have no metabolic flexibility, which means that 88% of overweight people, when they stop eating, cannot use fat as a fuel because the fat is trapped in their fat cells and it's blocked from getting out of the fat cells by an elevated insulin. And 88% of overweight people have an elevated insulin. If you want to get really scared, 99.5% of obese individuals are metabolically inflexible. Basically, every obese individual has no way of getting that fat, which is there out of fat cells because of an elevated insulin level. It's literally, like I write in the books, water, water everywhere and not a drop to drink. And that's why, for instance, when I was running 30 miles a week doing 5K, 10K, half-marathons on the weekend and going to the gym one hour a day, I was an obese individual. I was what was called a Clydesdale runner. And it didn't make any sense that I was doing all this and yet here I am just this giant fat guy. Well, imagine my surprise when I had my first fasting insulin level dropped. And my fasting insulin level was 16. Now that doesn't mean anything except that in general, the lower your insulin level, the less insulin blocks fat coming out of fat cells. The higher your insulin level, the more insulin prevents you, me, from getting to all that fat that we've stored. So normally, depending on the lab, insulin levels should be less than 10. The closer your insulin level is to one, the more metabolically flexible you are because you no longer have insulin blocking your ability to take fat out of your fat stores. So when I was metabolically inflexible with an elevated insulin level, it didn't matter that I was running all that much. It didn't matter that I was going to the gym one hour a day. No matter what I did, insulin was storing fat and wasn't allowing fat to come out. So it was no wonder I was a big fat guy. And I see this over and over and over again with my patients. And I profile one of them in the new book Unlocking the Keto Code, Miranda. And Miranda was insulin resistant. She actually had a fasting insulin level of 16. And Miranda thought she was following a ketogenic diet, a high fat diet. And was shocked that the more she followed a high fat diet, the more she weighed, the more weight she gained. And she was actually apoplectic. When I told her that the reason she wasn't losing weight was because she had a high insulin level. So she was storing all that fat she was eating and she couldn't get to the fat that she was storing. So this is the fundamental problem with metabolic inflexibility, the inability to switch over and actually get to that fat. Why is that so important? Well, again, mitochondria are in the business of producing energy, ATP. And normally, they're perfectly happy using sugar as a fuel. But when that sugar runs out, when you stop eating, and there's no longer any sugar, they have to be able to access fat. They have to be able to access that battery power to continue to make energy. So if you follow the logic and you have to produce ATP, and the only ways to produce it is either burn sugar or burn fat, and the vast majority of people can't get to the fat to start burning it because their high insulin level won't release it. It's no wonder that we see this massive increase in the diseases of aging. In other words, prediabetes, diabetes, dementia, memory loss, high blood pressure, coronary artery disease, even cancer. It's this inability to make this shift that we now know is driving almost all of our diseases of aging. And as more and more of us become overweight and obese, more and more of us are suffering the consequences of metabolic inflexibility. Now, I mentioned my fasting insulin level. And you've heard me before and you've read in my books that if I only had one blood test to predict my fate going forward, either on a day-to-day living basis or long-term, and I only had one blood test to choose from, it would be a fasting insulin level. And it costs about $8, that's it. Now, as I've written about before and I've talked about on this show, I get to see third-year family practice residents rotate through my clinic for a month. These are doctors who are about to enter private practice. They're about to go out and start servicing you. And so far, I've been doing this for about four years. Not one of these people in their last year of training has ever heard of a fasting insulin level, has never been told about a fasting insulin level. And what's shocking is, they know all about hemoglobin A1c. You probably know all about hemoglobin A1c because you're bombarded with commercials every night. I got my A1c under seven or I got my A1c down or I've got my A1c in my diabetes zone. The sad thing, after doing this for 25 years, I see a large number of people who may have a hemoglobin A1c, which basically looks at how you're handling sugars and proteins for the two months prior to the test, looking back in time. They may have a normal hemoglobin A1c. They may have a pre-diabetes A1c, which most doctors poo poo, but they almost universally have an elevated fasting insulin level. And when I show these residents, these young doctors, the correlation between this high fasting insulin level and what they would have assumed is a normal, healthy hemoglobin A1c, they're just shocked that nobody had ever told them about this because it explains so much about why we're missing one of the real causes of our current obesity epidemic, heart disease epidemic, dementia epidemic, Parkinson's cancer epidemic. You choose because almost all of these diseases in the end relate to whether or not your mitochondria can use both fuel sources, number one, equally, but probably more important, whether you can get to all that fat that you have stored. And until you lower your insulin level, you're not going to get to that fat. I'll give you an example actually from this week. I have a gentleman, actually two gentlemen, both of whom are my patients. One gentleman is thin, the other gentleman is obese. And they both eat, pretty much the same diet. And one of them is thin and one of them is obese. And they come in and they look at me and go, you know, this makes absolutely no sense. We watch each other eating and we pretty much eat the same stuff. And yet, you know, one guy's thin, the other guy's fat. As I showed in the new book, Unlocking the Key to Code, there's a fascinating twin study where they looked at twins who are obviously genetically identical. They carry the exact same genes. And despite the fact that twins carry the same genes, there are twins, one of whom is thin and the other whom is overweight or obese. And what they've done is look at the mitochondria of these two twins. And in the book, in the paper, the twins whose, the obese twins or overweight twins have mitochondria that are described by the researchers as lazy. Whereas the twin who's thin have mitochondria that are not lazy. They're really revved up. Now that doesn't mean the overweight twin was lazy. I certainly wasn't lazy when I was running 30 miles a week and going to the gym one hour a day. But my mitochondria, because of my high insulin level, couldn't use fat as a fuel. So it would appear to an outside observer that my mitochondria weren't very good at burning the calories I ate. And someone who was skinny looks really good at burning the calories they ate, even though they're eating the same food. So let's look at the insulin levels of my couple. Insulin level of the skinny guy is three. The insulin level of the fat guy is 22. And so even though they're eating the same amount of food, what's going on? Well, even though the two are eating the same amount, the thin guy can access all that food he's eating. Insulin stays low, so insulin doesn't store. Any of the calories he's eating is fat and he remains thin. And even when he stops eating, whatever fat he has immediately gets released for him to burn as energy is making ATP. The fat guy, higher your insulin level, the easier it is to store fat because insulin is the fat storage hormone. So they could literally eat the identical food and the fat guy would make fat out of that food and the skinny guy wouldn't. The other sad thing is the fat guy because of the high insulin level, when he stops eating at night, he can't get to all that fat that his skinny partner can because his insulin level is too high to let the fat out. So every day he's turning most of what he eats into fat and every night he can't bring that fat out. So you've got a tale of two individuals who are eating the same thing. One can't stop storing fat and can't get to the fat he's storing. And so we're working with the tricks that we talk about in the book to get that fat guy to stop storing fat to get his insulin levels down. So that kind of takes us to part two. If you're metabolically inflexible, where do you start? Well, one of the first places to start is intermittent fasting, time-restricted eating. Now, sounds like a great idea. And those of you who have listened to me, have read my books, know what time-restricted eating is. In general, the more you compress the eating window of when you start eating break fast, first meal of the day, to when you stop eating in the late afternoon or evening, and the more you can compress that down to about six to eight hours, the total eating window, the more metabolically flexible you become for two reasons. But the problem with an elevated insulin level is when you stop eating, the clock starts ticking for how long before your glucose, your sugar stores are gonna last before you normally should be able to switch over to burning fat. And that's somewhere around eight to 12 hours. So if you're metabolically inflexible and can't get to that fat, it's no wonder that when you wake up at seven o'clock in the morning, for instance, you're ravenously hungry, and you really need to get some form of sugar into you because you're literally running on fume, and so many of my patients, when we talk about, well, I want you to get to a point where your first meal of the day is at noon instead of seven o'clock in the morning, and they go, oh, come on, Dr. G, if I don't have something to eat by eight o'clock, my brain doesn't work, I have no energy to go to the gym, it's hard enough for me to get my kids off to school without getting something in my stomach. And for those of you who hear that and say, yeah, that's me, that's actually one of the most important signs that you are metabolically inflexible, and this actually should be a red light on your dashboard going, check engine, there's something really wrong. That's one of the first signs. The second sign is a lot of people who go on a low carb diet or a ketogenic diet, a high fat diet, often for weeks have low energy, they have a headache, they have a brain fog, and they're just, you know, they're hangry, they're, you know, they're angry and hungry. Why? Because most people have an elevated insulin level, most people are metabolically inflexible. And so even though you stopped eating sugar and starches, you can't get to all that fat you stored, number one, and all that fat you're eating still can't be utilized by your mitochondria as a fuel. And it just becomes fat like my poor patient Miranda. So what I want you to do, I'll hold your hand as we go through this, but instead of eating breakfast at seven, next week, Monday through Friday, let's eat breakfast at eight, come on. It's only one hour, you can make it, it's not gonna kill you, in fact, it's gonna help you. And then on the weekends, we'll take the weekend off. You can have breakfast at seven if you want to. The following week, I know you can make it to eight o'clock, let's go to nine o'clock for our breakfast, break fast. And let's do that for five days. Five days is all I ask Monday through Friday, and then we'll take the weekend off, you know, for good behavior. If you make it to nine that week, next week, let's go to 10, and we'll do it breakfast at 10 o'clock. Now, some of you may not be ready. You said, eh, I got to nine okay, but it wasn't a lot of fun. Let's stay at nine for another week. The more we can slowly adapt to this, the more your insulin level will slowly go down. And once your insulin level goes down, miraculously, fat is released from your fat stores. And miraculously, now your mitochondria have the fat available to them to burn and make ATP. They become metabolically flexible. Now there's another little proviso in this, and that gets into unlocking the keto code. So normally, if you're metabolically flexible, all of your cells in your body, with exception of one type, can burn fat as a fuel and burn sugar as a fuel. No problem, either way works fine, except for the brain. Now, the brain, as many people know, have this special membrane around it called the blood-brain barrier. The blood-brain barrier is there to prevent big particles from getting into the brain where they don't belong. Fats, free fatty acids, are big, and they can't get through the blood-brain barrier. So even though all the rest of the cells in your body, your heart, your muscles, everything can use free fatty acids as a fuel. The brain would love to use them, but they can't get into the brain because of the blood-brain barrier. So what to do? Well, luckily we have a wonderful work around in that free fatty acids, if you can get them out of your fat cells, if you have a low insulin level, can go to the liver, and the liver can convert free fatty acids into ketones, ketone bodies. The liver cannot use ketones as a fuel. So the liver says, well, okay, I made these things, I'm gonna throw them out into the bloodstream, which is great news because ketones are actually water-soluble, small, fat molecules that can get through the blood-brain barrier. And neurons, your brain, can use ketones as a temporary fuel until such time you eat again, hopefully the next morning, or they can use it for a long time until you find that buffalo or you find that fruit tree. So ketones were actually the stopgap for the brain until you found your next source of food, which could have been a very long time. But you cannot generate ketones unless you release free fatty acids from fats and you can't release free fatty acids from fat cells if your insulin is elevated. That's the catch 22. Now the way around that is kind of part two in all my books, in the ketogenic part of the book, is that there is a miraculous workaround for generating ketones. And that's medium chain triglycerides, MCTs. So MCTs are short chain fats that are actually absorbed completely different than any fat that you eat directly through the wall of your intestine. And rather than going into your bloodstream, they go directly into your liver, where guess what, no matter what your insulin level is, no matter what your metabolic inflexibility is, MCTs are converted into ketones. Why is that so important? Because even when you, like most people, can't release fats from fat cells, MCT oil, or MCTs from other sources, which we'll talk about in a second, can make ketones in your liver that can then get into your brain and keep you from having that crashing feeling, that hangry feeling, that run out of energy feeling, until you eat again. And it's one of the best tricks there is. Now, for my female listeners, MCT oil often gives you a queasy stomach, a bit of nausea, sometimes diarrhea. So number one, you wanna start off slow. Try a teaspoon of MCT oil first. Try to work your way up to about three tablespoons a day. With my female patients, MCT powders seem to work much better than MCT oil. And there's a ton of great MCT powders, they're usually available as coffee creamers. You can stir it right in your coffee so that you can start getting the benefits of ketone production. First thing in the morning, without eating. And that's what we're trying to establish. Now, the second thing that was a real shocker from unlocking the keto code is that sheep and goat milks, 30% of the calories are actually medium chain triglycerides. And fun fact, MCT oil is named after the Latin word for goat, capra. So there's capric acid, caprylic acid, and so forth. And so you could have goat or sheep yogurt, plain please, or a piece of goat or sheep cheese. And you would actually be eating very flavorful MCTs which would go to your liver and make ketones even though you're having a piece of cheese or some yogurt. In fact, the miracle of MCT oils, MCTs in general, is that you could actually have a carbohydrate meal which would be anathema to a ketogenic diet and have MCT oil with it. And you would make ketones which could provide an alternative fuel source for making ATP and keeping your brain alive. So using MCT oil and slowly, slowly, gradually, pushing off breakfast to as close as I can get you to noon every day will break this log jam of metabolic inflexibility. Now, why should we do this? Well, the point of all of this is that metabolic inflexibility underlies pretty much most of the bad things that are going to happen to us. There's beautiful evidence that cancer is a metabolic inflexibility disease. There's even more compelling evidence that dementia, memory loss, is a metabolically inflexible disease process. And think about that one. That one's almost obvious. If your brain cells have to have sugar to survive because they can't get to fat because your insulin level is high, by the time you have stopped eating for about eight hours, your brain cells are starving to death every night even though you're overweight or obese. They literally have nothing to use as a fuel because you can't make ketones to keep them alive. So is it any wonder that we're seeing this epidemic of memory loss and dementia that we never saw before? In fact, think about this. When we see men or women with elevated insulin levels in their fifties and sixties, it's a guarantee, a guarantee that you will have accelerated memory loss in your seventies and eighties. Are you listening? It's a guarantee. Why? Because it's a guarantee that your brain stars to death every night. And is it any wonder that Americans currently eat 16 hours a day from the minute we get up to our late night bedtime snack because we're constantly trying to keep our brain from dying. All right, that's something to think about. How to learn more about this? Get unlocking the keto code. It's a national bestseller. Thank you very much for everybody who's done that. We made the USA Top Books, USA Today Top Books this week. It's number one on Amazon in nutrition and ketogenic diets and low carb diets and immune system health. Thank you all very much. It's a great read and you'll not only unlock the keto code, but you'll break your metabolic inflexibility and you'll look forward to not only immediate good health, but great health long-term. I hope you enjoyed this episode of the Dr. Gundry podcast. Make sure to check out the next one here. I write about these three fasting hacks that you can do that reduce your suffering, reduce your hunger, give you more energy and more focus. So fasting becomes an effortless, easier part of the day that gives you more energy than eating a muffin in the middle of the morning.