Rise In Obesity & Disease: How To Fix Your Diet For Overall Health & Longevity | Dr. Steven Gundry

There's no doubt that our epidemic of Alzheimer's and Parkinson's and memory loss is laid at the feet of our metabolic inflexibility. Dr. Steven Gundry, welcome back to the show. Tom, thanks for having me. Great to be here. Dude, it's really good to have you. I really enjoyed this book. As I've said many times on this podcast, I judge a guest by whether the research is going to move me forward in my life and Unlocking the Keto Code is really intriguing and I'm super grateful that I'm going to get to drill down on some of these. So, keto changed my life. So, I used to struggle profoundly with inflammation and when I discovered keto, it changed everything for me. It changed my relationship to hunger, to inflammation, to all of it. And in the book, you make it very clear that we don't understand some fundamental things about ketosis and ketones. And so, let's start with what don't we understand? Well, I guess the best place to start is what we thought we understood about ketones. And ketones and ketosis have been known about since the late 1800s. And I hope that a lot of people in the keto community know that the ketogenic diet, the the actual word ketogenic diet, was founded in 1930 at the Mayo Clinic as a treatment method for children with seizure disorders, epilepsy. How did they figure that out? Because that does not seem like a super obvious, at least for me as a lay person, not a super obvious conclusion to draw that that's sugar based. Well, what they found was that children who had severe epilepsy spent so long post-seizure and it's got a medical term called postictal state where they're okay, they're not seizing, but they're not really waking up. Um and they spent so many so many hours in this post-seizure state, repeated seizures, and then just kind of in a coma that they didn't eat very much. And they were literally starving. And they made the observation that kids who were starving because they had so many seizures paradoxically had less seizures the more they were starving. And so researchers first at Boston, and then at the Mayo Clinic, said, "Wait a minute. We know that ketones happen when you're starving. That's when it happens. So, it must be that ketones are doing something to these kids' brains. And are there other ways other than starvation to produce ketones? And one of the ways they found was, well, look, if you deny carbohydrates and really cut back on proteins and give kids mostly fat to eat, then they will make ketones even though they're not starving to death. These kids did very well on a ketogenic diet. 50% of them had complete seizure control. Uh recently, I've got a young man who's a high school student who despite two meds, uh was still having seizures so bad he was in special ed and falling way behind. His mother brought him to me in my clinic in Santa Barbara. And we put him on my ketogenic diet, which is kinder and friendlier. And the kid woke up. He's off of his medications. He's now playing any kind of keto before that? No. Okay. Not at all. So, went from meds to meds and keto or keto only? Keto only. We took him off his meds. Wow. He woke up, uh wasn't, you know, drugged. And now he's taking advanced classes and he's actually playing soccer uh for his soccer team in high school. Mhm. And he could not do any of this. I mean, can you imagine a kid with a severe enough seizure disorder being on two meds now actively playing high school soccer. Um just by changing back into vogue? So, I had somebody on the show when this was still Inside Quest. His son had um seizures, epilepsy, and he said they didn't even tell him about ketogenics because they said compliance was so low that they didn't even mention it to parents anymore. And he had to like go do his own research and he found some obscure article in like a journal from the 1950s. He was like, "Hold on a second." Did the same thing, put his son on, boom, total total remission. Yep. Has not had a seizure in like 20 plus years. Yeah, well, that's a great point. So, the ketogenic diet, the high-fat ketogenic diet for seizures once phenobarbital and Dilantin came and the new seizure drugs came uh it died uh because kids couldn't do an 80% fat diet. They actually had growth retardation and they just wouldn't follow it. So, what happened actually in the '80s was people discovered medium-chain triglycerides, MCT oil. And this oil was the miracle oil that some of these TV shows were done. And what they found was that MCT oil could convert into ketones in the liver and we'll get into why why that happens. And they found that if you put kids on a MCT oil-based diet you could give them far less MCT oil, far less fats, and you can give them tons of carbohydrates, which I'm a parent and grandparent now, and you cannot deny children carbohydrates as much as you as much as we think we should. So, these kids could have more carbohydrates, more protein, they could grow and develop normally, but they'd still stop their seizures. Yeah. How much do you have to reduce the carbohydrate intake if you're using MCT oil? You can't just You can't just add MCT oil, right? You still have to modify. Really? So, no matter how much carbohydrate I'm intaking What's amazing is, and this is human studies, you can take a tablespoon of MCT oil, which is not much, and you can actually, within a half an hour, generate a generous amount of ketone body production from the liver. 0.5 At least 0.5, 0.8, 1. Wow. From 1 tablespoon of MCT oil. I've never tried it, so I can't deny it, but man, knowing how hard it is to produce ketones without it, that's scandalous. Yeah, and that was the beauty of this. And so, when I, you know, I actually started writing this after after I wrote The Energy Paradox, which we've talked about, and I was trying to explain, you know, how where ketones fit in to all this in terms of energy production. And as you know, I like to back up what I say with research, either my own or somebody else's. And as I was trying to explain how beneficial ketones were for energy production, for protecting mitochondria, for turning mitochondria into fat-burning efficient machines, and I started looking at, you know, the research to back up what I was saying, I went, "Holy cow. Uh I'm wrong this and so is everybody else. Ketones aren't some fantastic that? Most people cannot, especially if they've talked about it publicly, they can't change their position. Hopefully that's make makes me one of the more believable nutritionists around because I'm always willing to say I was wrong. So what was the first thing that made you go, "Wait a second, I don't think we were on the right path." Well, one of the most, you know, amazing things. And I I I've had a ketogenic diet in all my books for last 20 years. I've had a ketogenic program for my patients. And looking back, when you actually look at the list of things I allow on my ketogenic diet, there's tons of carbohydrates. And yet it works extremely well. And I've been using MCT oil for my program from kind of day one. So I and I've written that ketones make you an efficient fat burner. And I firmly believe that. So I was going to prove how ketones actually make your mitochondria incredibly efficient at making energy. Right. And probably the best way to explain this is we know that ketones were discovered during starvation. And nobody quite figured out why they were produced until the 1930s. But then, how ketones came about to be known what they did really started in the late 70s, 80s, up to the year 2004 at both Harvard with George Cahill and Dr. Owens and Dr. Veech at the NIH. And they wanted to know, okay, well, what were ketones doing? They're We We do things by accident. And so they started to look at okay, human beings clearly have starved for multiple times. We didn't have As a species. As a species. We didn't have 7-Elevens next to us. We We didn't have fast food. We We didn't have refrigeration. We didn't have storage systems. And we had to find or kill food. And there were famines and there were times not much food. So we were designed when we found food to store a lot of it as fat. And I've written about this in previous books. Great apes, interestingly enough, only gain weight during fruit season. And fruit season doesn't happen year-round in a jungle. It really only happens in the summer and early fall. We gained weight because the winter and spring was actually times of less food. So it became beneficial to take fruit and convert it into fat so we can make it through the winter. And that defect, it's actually a genetic mutation that allowed great apes to do that, we inherited as well. So we're really good at storing fat. In fact Yes, we are. Yes, we are. In fact, we're I'm better than most. We're called the fat ape for a reason. We We We best all apes at at storing fat. So when we don't have any food, normally, and I talk a lot about in this book and you and I have talked about this, most of us should have metabolic flexibility in our mitochondria. And mitochondria are the little energy-producing organ- organelles that take we the food we eat and produce ATP, our energy currency. And mitochondria, for anybody that doesn't know, are like aliens inside of our cells. They have their own DNA, which is crazy, and I still don't understand how that's possible, but nonetheless, it is true. And at some point two cells combined and they were able to handle oxygen by the mitochondria wrapping inside of the cell, which is bananas. There's actually a gaggle of them inside of every cell. Yes, there's bunches of them. Unlike our high school biology textbook that might have said shown one or two mitochondria per cell, there can be thousands of mitochondria. And they're actually engulfed they're engulfed engulfed bacteria from 2 billion years ago. And they actually carry or write their own DNA. And the cool thing about that and important part of the book is that mitochondria can divide and make more mitochondria without the cell they're living in dividing. So, if a mitochondria gets the right stimulation, and that's part of the book, they'll make a lots more of themselves and to share the energy load. So, getting back to starvation, normally you and I, hopefully, when we run out of sugar, we can immediately start burning free fatty acids. And that's the flexibility you're talking about. You can burn sugar, can burn fat. We should be a hybrid car. If we burn gasoline, we'll call that sugar. When the gasoline runs out, we've been storing energy in our battery. And when the gasoline runs out, we switch over to battery power until we go fill up at the filling station. Unfortunately, here's the weird thing. 50% of normal weight individuals have no metabolic flexibility. 50% of us Just because of modern diets. We're eating all the time, we are never in a quote-unquote starvation phase. Correct. If you're If you're overweight, 88% cannot shift between burning sugar and fat. If you're overweight, uh if you're obese, 99.5% of people cannot shift to burning fat as a fuel. And what's What does that mean? Why does that matter? Well, you normally, if you and I stop eating tonight, uh whenever, about 8 hours after we stop eating, we should actually run out of glucose as a fuel, and we should shift over to burning free fatty acids and ketones as a fuel until we get our next meal. That's normal. And by 12 hours of not eating, we actually ramp up ketone production to pretty much take over our brain's need for fuel temporarily. And your brain actually, if it runs out of sugar, starts dying. So, the implication for that brain is never without sugars? Believe it or not, the brain normally would run out of sugar in about 8 hours after we stop eating. Normally runs out of sugar. And it shifts over to using ketones as a temporary fuel. The reason it can shift over is once we stop eating, we start liberating free fatty acids, fat, from our fat cells. So, you're saying it would die if we didn't have ketones? Correct. Got it. Okay. So, normally, those free fatty acids come out of fat cells. Every one of our cells, except the brain, can use free fatty acids as a fuel and use them very well. And this has been, again, proven at Harvard and the NIH. Our muscles love free fatty acids. My research on the heart, years ago, showed that the heart prefers burning free fatty acids instead of sugar. It's favorite fuel. In fact, we protect the heart during heart surgery by putting fats into the heart. How? Uh through the veins and the arteries. I invented You You inject fat? Yeah. Yeah, well, we dissolve it in our cardioplegia. Yeah. Whoa. So, um without that metabolic flexibility, then what happens? What happens is what we're discovering right now is that your brain cannot get life-saving ketones to burn as an alternative fuel. And your brain runs out of glucose as a fuel because you don't have any available. And your brain for several hours a night until you eat again, neurons die. And there's no doubt that our epidemic of Alzheimer's and Parkinson's and memory loss is laid at the feet of our metabolic inflexibility. Mhm. Okay, so that is certainly terrifying, but means that we can do something about it. So, going back to where we left off. So, we go into starvation mode, we start kicking off these ketones. That feels like the sort of story up to before this book. People understood that. So, where do you begin to go, wait a second, we have a problem here? Okay, so we can make ketones. We make ketones from free fatty acids. They go to the liver and the liver generates ketones. Now, liver, interestingly enough, can't use ketones as a fuel. They are incapable. They don't have the enzyme to do it. Can it use free fatty acid? Yes. Okay. Liver loves free fatty acid. Which it gets as fat is oxidized, we get free fatty acids, and we can snatch them out of the bloodstream and use them. Right. And they're a great fuel, fabulous fuel. So, what everybody thought But they can't cross the blood-brain barrier. That's the problem, right? Cuz they're too big and fat, if you will. So, but as luck would have it, ketone bodies, ketones, are water-soluble small fats. And they can get through the blood-brain barrier. So, the brain can use ketones until glucose arrives the next morning or for several days. Now, that piece of the puzzle wasn't known. So, people like Cahill, people like George Veech, said, "Wow, ketones are clearly what made humans survive for a long time because we could use them as a fuel without burning up our muscle to make glucose. We can convert muscle protein into sugar. It's called gluconeogenesis. They actually showed that if you literally had to live on glucose as a fuel, your muscles would be gone after about a week of starvation. only way for gluconeogenesis to happen is from muscle tissue. Yeah, but you can also make gluconeogenesis from breaking glycerol molecules off of triglycerides and convert that into glucose. So, there is a way to get sugar from fat. Got it. We're really good at turning sugar into fat. We're really bad at turning fat back into sugar. We just don't have the enzyme system to do it. So, when this ketone was found, everybody said, "Wow, that explains everything. We can run on ketones and be great." Not so fast. Dr. Owens at at Harvard showed that at full ketosis, Human beings can only meet 30% of their calorie needs by burning ketones. The rest have to come from free fatty acids and glucose. So, that's kind of weird if they're such a great fuel. The brain, it turns out, even at full ketosis, only 60% of the brain's needs can be met by ketones. And the brain still needs 30 to 40% of its fuel as glucose, even at full ketosis. So, when I read that research, I went, "Well, wait a minute. This is not some super fuel. The body doesn't even view it as a super fuel. But, we don't do things for, you know, not a good reason. What the heck are ketones actually doing that's so beneficial? And that's what when I went down the rabbit hole and came out with Unlocking the Keto Code. Because ketones are not a super fuel. They are actually a signaling molecule that tells mitochondria to protect themselves at all costs from damage and to save themselves at all costs if you are starving to death. Because, quite frankly, if we're starving to death, if you don't protect your mitochondria that make energy, that's the end of us. You die. You're done. So, I read a silly little paper. It's actually maybe the one of the most important papers I've ever read by Dr. Martin Brand in the year 2000. And it's a simple paper called Uncoupling to Survive. And I hope all your viewers and listeners dig it up, you know, check with Google, it's there. And what he said was it just you know, talk about a paradox. And he said, "Look, in extremis, the mitochondria has to survive. So, the mitochondria is instructed by ketones to literally start wasting a lot of the calories that it would normally process into ATP and throw them away. My brain broke when I read that part of the book. I know. And I took down a note. I was like, "Hold on." And I know you answer it, but I was like, "There has to be an evolutionary advantage to this. I cannot see how in a moment of starvation we would want to kick off extra energy and {quote} {unquote} waste it. At least for me, this is all coming together at a moment where it feels like there's these breakthroughs in science which are all pointing to the depression of the mitochondria and their ability to produce energy in a good way, which is weird. Yeah. Yeah, I you know, I and most ketogenic diet experts have always taught that you know, ketosis, you teach your mitochondria to be energy efficient, to get energy out of every last calorie cuz you're starving to death. So, you need to turbocharge and supercharge your mitochondria to eke out every last drop of energy. And that makes incredibly It's intuitive. It feels right. really good. But what Brand said, "No, you're wrong. They do the exact opposite." And you go, "No, no, no, no, no, no. There's no food. Why in the world would you waste food?" So, what he showed was and I I have a fun time in the book talking about the Mito Club. Yep. Let's hear about it. Yeah, so so mitochondria make energy by energizing electrons and protons in this long tube called the electron transport chain inside of mitochondria. And I likened this long tube to the hottest hippest club in town where people go to the club to couple, to meet someone. To hook up. To hook up and if they hook up, they exit the club and let the imagination run. That's my energy. Get some energy. Get some energy. And this club is is hot, it's crowded, there's there's hormones through the roof, there's alcohol flowing and everybody's bumping into each other and everybody's trying to couple with everybody else. Normally oxygen should couple with a proton and exit the back door and make ATP. Oxidative phosphorylation, some people have heard. But because it's crowded and there may not be a lot of available protons that people want to couple with electrons could also couple with oxygen and they're not supposed to and they get they make nasty free radicals and reactive oxygen species and punches start being thrown, chairs are flying and beer is flying and there's bouncers in the club to try and calm this down and everybody knows about antioxidants. Turns out there's only two antioxidants in mitochondria. Surprise, surprise. melatonin, which most people don't even know is an antioxidant, the sleep hormone, and glutathione. Um there's only two. So, they're the bouncers. So, getting back, that club is hot, it's energy, there's damage being done. You got to keep this club under control. So, everybody's trying There's only one way out of this club through this back door. But, people are getting frustrated, and they want to leave because it's a bad day to couple, and they're not coupling. So, it turns out there's emergency exits in the club, where things get too hot, if people get too frustrated, they can push open an emergency exit and leave the club. The mitochondria have emergency exits. There's actually five emergency exits in our electron transport chain. And they're controlled um by uncoupling proteins. Now, I spent 6 months trying to figure out a better word for uncoupling. Uh and cuz people think of uncoupling like Gwyneth Paltrow getting divorced. I uncoupled my marriage. Uh but uncoupling means that instead of joining a proton with an oxygen molecule to make ATP, the proton leaves the club, leaves the mitochondria without making energy. So, what Brand showed, and others have subsequently confirmed, is that mitochondria, at rest, you and I sitting here, 30% of all the calories that enter our mitochondria right now, are going through these emergency exits and never making ATP. 30% just here. Normally. Normally. And you say, Not in starvation mode, just normally. You and I sitting here. And you go, "What a stupid idea. You and I have to eat 30% more calories every day just to make our normal amount of ATP." And you go, "Oh, why would I do that?" Well, it turns out generating heat is what those calories do. And you and I are warm-blooded animals. And in fact the only way we generate heat? It's actually the only way we generate heat. Okay, so the emergency exit is how we stay warm. Correct. And it turns out that brown fat, which a lot of people have heard of, brown fat is our energy, our heat-producing fat. Does that mean that brown fat has more mitochondria in it? It's so many mitochondria that it looks brown under the microscope. Okay. They are crammed in there. And we thought brown fat only existed in babies to keep them warm. Uh and there is a lot of brown fat in babies. But we now know that you and I actually have brown fat, and the more brown fat we have, the healthier we are. And we'll get to that. And what Brand eventually showed is if you look at the super old people, folks 105 and above, who are thriving, they have the most uncoupled mitochondria of anybody. And you go, "What? So, wait a minute. Uncoupling mitochondria must have huge benefits that none of us knew about." Let's get back to ketones. So, ketones tell mitochondria that trouble is a foot and to protect yourselves at all costs. So, the first thing you do, mitochondria, is don't damage yourself by making energy. And making energy is very damaging to my mitochondria. So, waste you know, making energy. Waste more calories. Protect yourself. Cool it a bit. But secondarily, that makes no sense because you got to have enough ATP to survive. So, simultaneously, the mitochondria is instructed to make more mitochondria to share the workload. Now, think about this. The Iditarod is, you know, being run and let's have a one one dog dog sled. Well, yeah, the dog can pull the sled, but he's not going to go very far before he tuckers out. But if you hook six dogs to the sled, each dog has a sixth of the workload that one dog has. So, they can go a lot farther with six of them doing less work. Now, the consequence of that is they actually are going to eat more food than the single dog to accomplish the same thing. So, now you go, "Wait a minute. A ketogenic diet is a really good weight loss diet." Can't be because the mitochondria are more efficient because if they're more efficient, they can get more calorie more food more energy out of calorie. energy. Right. And in fact, you lose weight. So, what happens is you actually in a ketogenic diet, if you do it right and uncouple your mitochondria, you waste fuel. You feed six dogs instead of one. And that's where the benefit of ketosis comes from. What's up, everybody? Tom Bilyeu here and I have a question for you. At the start of this year, you likely set some goals for yourself and I want to know how those are going. Most people give up on their goals and dreams by February, but I have some good news. If you're not on target to succeed at the things that you want to achieve this year, it's not too late and trust me when I say you are not alone. Everyone gets stuck and loses momentum towards their goals at some point, myself included. If you know what you're doing and you're willing to take massive action though, you can get back on track. The trick is not to think about being stuck as a problem with your motivation or to interpret your lack of results that you're getting as a sign that you're not smart enough. The trick is to recognize that the game that you're playing is a game of neurochemistry. It's about managing the way that you think about yourself and framing things in the right way. If you use your brain more effectively, repeat things that empower you, you can actually find ways to solve problems faster, create positive habits and behaviors that you know are going to help you reach your goal. I want you to take massive action right now, so I pulled a workshop from Impact Theory University called the six steps to getting unstuck and I want you to watch it right now. It's going to help you get back on track with your goals and make the rest of this year your most successful ever. To watch it, go to unstuckclass.com and register for access. I'll walk you through the same process that I use to get through obstacles and make fast progress towards my goals whenever something slows down. All right, guys. Enjoy this and be legendary. Take care. Okay, so now I'm trying to pin down the evolutionary advantage. So, I'm in starvation mode. Yep. That's when I'm producing ketones. Why on earth would starvation mode trigger my mitochondria to waste more energy and become less efficient? To protect themselves at all costs. So, it's purely a protective mechanism. It's an evolutionary protective design to save the mitochondria at all costs. Dear human body, I cannot keep taking this rate of damage for you. I have to conserve. The only way to conserve is to release more of these out of the emergency exit, so I don't have to process them, take on the free radicals, and all the damage. So, go out. My temperature theoretically should feel like it's going up subjectively. Uh believe it or not, a lot of people do. And we'll we'll get into the ammunition workers in France and Germany in World War I, which actually proved his theory. Nobody knew that that proved his theory, but uh that's what happened to them. Yeah, you actually should raise your temperature. Um just as a a fun fact, ever notice when you have a cup of coffee or a tea, even if it's iced coffee or iced tea, uh many of us go, "Gee, you know, I'm kind of glistening even though I'm having an iced coffee." Uh you actually produce more heat having a cup of coffee because both the caffeine and the polyphenols in coffee and tea uncouple your mitochondria and have them generate heat. Huh. So interesting. Okay, so I my mitochondria is protecting itself by uncoupling. They're getting rid of this stuff. They're making more of themselves Okay. to share the workload. Each one is working less hard so that they aren't being damaged. Right. But you're recruiting more mitochondria. And the amazing thing is, during ketosis or other things that stimulate mitochondria to uncouple, you actually generate more mitochondria. And mitochondria in starvation will devote all the protein manufacturing in in cell to make more of their proteins and they'll actually not make muscle protein. Screw the muscles, they're energy hogs. We're not going to build muscle if we're starving. We are going to build more mitochondria to work less hard. Screw everybody else. All right, here's where this gets complicated for me though. So, that all makes sense. I'm I'm tracking with that. Uh in the book you talk about how it does um the way that it further stops the muscles from taking the energy is that it makes you insulin resistant. So, and when you look at like what happens with fructose and uric acid, there's a similar thing going on, which is hey, raise insulin, which seems like it's bad in a modern context, but from a survival famine context actually brilliant because it traps the fat, makes you use it more slowly, it's hard to get out. Yep. To make sure that you don't burn through the energy and end up dead, but the munitions facility that you alluded to, the way that we end up dead real fast is this process on a runaway train. Is it just that I can exit people out the emergency exit way faster, way more dramatically than I can stop the fat from pouring out? Walk people through what happened in the munition factory. Okay. Um in World War I, it was noted that munition workers in France and Germany who were assembling shells and working with gunpowder were extremely thin, even though they were eating huge amounts of food. And they could not keep weight on. And they were running a temperature 24 hours a day. And it wasn't until the late 1920s when they realized that these guys' a metabolic rate, BMR, was elevated. And it took a couple of doctors at Stanford in 1930 to say, "Son of a gun, we've discovered the compound that did it in these munition workers." And it was called 2,4-dinitrophenol. And keep that word phenol in everybody's mind. We'll come back. Oh, yes, it will. And it's called DNP. So, they actually said, "Oh my gosh, DNP raises the metabolic rate, and it is the world's best weight loss drug that nobody's ever heard of." So, in the 1930s, in America alone, over 100,000 prescriptions for DNP were written by physicians. And it was a miracle weight loss drug. You took a little bit of DNP every day, you'd lose a pound a week. That's insane. But, if you took a lot of DNP, you could lose 5 lb per week. You talk about a miracle. And just a little bit more, and you can be dead. Yeah, and now here's the problem. What happened was, as more and peop- more and more people got on the bandwagon and saw they could lose a huge amount of weight, people were running temperatures. They started noticing that thyroids were having a problem. Then, a lot of people developed cataracts. And this was before cataract surgery. And as I joke, can you imagine being able to fit into your skinny dress and not see how good you look in the mirror? Uh cuz you're blind. And then people started dying, dying like flies. And so, the FDA, uh in the late 1930s, 1938, as one of their first official acts, banned DNP for sale. But, it turns out that in 1978, it was discovered that DNP worked because it was the first known oral mitochondrial uncoupler. And DNP was so effective because it literally turned human beings from being Toyota Priuses, which are very fuel efficient, to being Ferraris, which are incredibly fuel inefficient. Now, as I talked about in the book, there might be reasons you and I would want a Ferrari rather than just wasting fuel, but the point is we these people threw fuel out all these side exits of their mitochondria. What does it become when it takes the emergency exit? It actually produces heat. That's why all these people were running a temperature. Kicks off as just heat, nothing else. In fact, looking back, um at Gundry MD, we have a number of products with thermogenic compounds. Compounds that we've known for years produce thermogenesis. Make heat. Lo and behold, every one of these compounds uncouples mitochondria. And lo and behold, that's why they're thermogenic compounds. They make heat. Okay, so now I think we come back to phenols, polyphenols. Specifically, what are those, why do they matter, and how do we begin to get into the new friendlier ketogenic diet? So, uh DNP, dinitrophenol. Phenol. Hmm, where have I heard that word before? Polyphenols. Polyphenols are used by plants to protect their energy producing organelles, which are their mitochondria, but they're called chloroplasts. So, let's go back to us for just a second. Oxygen, we have to have oxygen to make ATP normal. Oxygen is very damaging to our mitochondria. All these free oxygen radicals, blah, blah, blah. So, we can't live without oxygen, but we can't live with with it. And so, we have to, you know, sop up the damage the oxygen it does. Plants, on the other hand, have to have sunlight. And they kind of reverse engineer. They take photons from sunlight, combine it with CO2, and they make glucose and ATP. Sunlight is damaging to the plant mitochondria, the chloroplast. So, they actually generate polyphenols to protect their mitochondria from damage, their chloroplast. We get to see every fall the polyphenols in plants because the green chlorophyll goes away, and all those beautiful colors of yellows, oranges, reds, dark colors are the polyphenols that the plant generated to protect and uncouple the mitochondria plants. And it turns out the way they protect the mitochondria is to uncouple them. To make them work less hard. And the less hard their mitochondria work, the less damage sunlight does to them. Now, we eat plants, and the polyphenols in plants do two things. Number one, we don't absorb polyphenols from plants very well. But our bacteria actually love polyphenols. They're actually a prebiotic fiber for bacteria. And the bacteria then convert those polyphenols into absorbable polyphenols, which then go to our mitochondria and uncouple them. It's I can Every time I say this, I hear The Lion King, The Circle of Life playing in my head. You know, you know, we eat the plants, but then we die and the plants eat us. So, the plants are protecting themselves with polyphenols. When we eat the plant polyphenols, we uncouple our mitochondria the same way. There's the benefit of polyphenols. Okay, so they are technically we're getting like a metabolite of the bacteria processing the polyphenols. Correct. It It isn't showing up as a ketone. So, how many things trigger the uncoupling? So, we know ketones do it as a signaling molecule. We've got a whole host of polyphenols. Are some polyphenols better? So, a whole host of polyphenols. You You choose the polyphenol, I'll show you a paper that shows the action of that polyphenol is to uncouple mitochondria. I'll give you from last week. Um one of my compounds at Gundry MD is called Total Restore, which is a my humble opinion a really good gut repairing compound, gut wall compound. One of the things that I used long before I used that was a compound called wormwood. And people probably have heard of wormwood. It's in a lot of compounds to repair the gut. And just for fun, last week, I I saw a paper that a type of wormwood uh worked by uncoupling mitochondria. And I went, what the heck? I didn't know wormwood could do that. So, I started Googling wormwood and uncoupling mitochondria. Do this in your spare time, great fun. And lo and behold, five papers come up that wormwood mechanism of action is uncoupling mitochondria. And so, you start going down this this rabbit hole and you find out that there's literally just one thing that makes all the difference in a person's health and that is hitting the right dose of mitochondrial uncoupling and getting the compounds that will do that. And just to pique everybody's interest, there's an interesting theory of aging called the rate of living hypothesis. And the rate of living hypothesis is that basically you only have so many calories that you're granted in your life. They can process. Yeah, if you use up those calories quickly, that's the end. If you use up those calories slowly, that's great. And it fits pretty good. Little tiny animals don't live very long. They have really super high metabolic rates. Big animals like an elephant live a long time and they have fairly low metabolic rate. The problem with that theory is birds. Birds are very small in the scheme of things. But a hummingbird in captivity, which has one of the highest basal metabolic rates measured, can live 10 years. A parrot can live 80 to 100 years. Yeah. Guess what birds do better than any creature? Mitochondrial uncoupling. Bingo. There it is. They have the most uncoupled mitochondria of any species. Okay, now because I've read the book, I feel like I'm cheating a little bit, but uh so birds probably are dinosaurs that crossed. And so are we assuming that due to asteroid impact they became birds because they were already good at mitochondrial uncoupling, and that's how they were able to survive that period? I think it's a beautiful theory. I don't think anybody's actually, you know, actually spouted that out loud. But, you know, I mean, they are the last dinosaurs. That's very interesting. So, given that we are descended from mammals that also survived that period, it certainly makes a lot of sense that we would have survived if we already had that ability. And then I know humans, like by the time we became humans, there were twice that I think we were forced through these really narrow Yep. periods where there were very few humans left. Yeah, we were down 6,000 years ago, we were down probably to one woman and probably a few guys. It got that small? Yeah, she's mitochondrial Eve. All of us can be traced back to one female. Woah. Yeah. All of us. And, you know, just just so everybody knows, mitochondria actually uh they have their own DNA, their own genome. Mitochondria are only transmitted from the female. Uh you and I know, we're just drones. We we have no useful purpose other than being a drone. So, we we don't give any mitochondrial DNA. So, you can actually look at mitochondrial DNA. So, there's mitochondrial DNA in the egg. Yep. That's crazy. Yeah, but there's none in sperm. Uh no mitochondria go into the egg. That's really And what's really cool, and I've talked about this before. I mean, what's really We get all of our microbiome initially from our mother passing through the birth canal, hopefully. Yep. And so, our bacteria are female. And our mitochondria are female. And as I've talked about, and other people have proven, these female bacteria talk to their sisters, the female mitochondria. And they literally text each other. And that language was discovered, and got the Nobel Prize, um of postbiotics. And I talk a lot about postbiotics, as well. The communication system between the microbiome and their sisters, the mitochondria. And it's like, I mean, it's crazy. I mean, the design You just have to sit there and and marvel at the design. And then you start marveling at, "Okay, how do we tweak the benefits of this design? How do we maximize the benefits of that design?" And that's why one of the cool things is, yeah, we can uncouple mitochondria via a ketogenic diet, a high-fat ketogenic diet. No question about it. But do we want to do that 24/7? No, because eventually, like you mentioned, you will become insulin resistant to stop the muscles from stealing the calories. And you'll eventually start losing muscle mass, eventually, if you continue 24/7 ketosis for a long time. So, you want to cycle in and out of ketosis on a 24-hour basis. And book shows, "Okay, here's some tricks. Um let's do intermittent fasting, time-restricted eating. Let's stay in ketosis for 15, 16 hours a day. So, what window do you recommend? So, uh Dr. Mattson from the NIH, from the National Institutes of Aging, wrote a beautiful paper a couple years ago, um that shows probably 6 hours is the best window. Okay. 6 hours of eating. Um 18 fast, 6 eating. 16, yeah, fast 6 hours. Does he have an opinion on number of meals in the 6 hours? It actually doesn't matter. And I go into that again, there's a lot of fun nerdy stuff in here. Uh a guy by the name of Rafael de Cabo, also at the NIH, showed that all the calorie restriction literature, and calorie restriction, you know, cutting 30% of all the calories you eat every day, is really the only bonafide proven way to extend lifespan across multiple species. The problem is it's unsustainable. Um there is a calorie restriction society in the United States. Uh It's hilarious. They're they're miserable individuals. They're cold. They They're miserable. They're hungry. Uh Why aren't they warm? Because if they're putting themselves in starvation mode, they're triggering this whole thing. They've literally now gone into a thrifty gene mode. They're so far down the line. You pass through this. Correct. Then, you know, they're they're so far down the line. But de Cabo said, "Hey, wait a minute. I think we've got this calorie restriction wrong because we're controlling the animals' food, and we're putting the food in their cage, and we're giving them X amount of food. I wonder if the time of day that we put the food into the animals' cage, and the time they're eating the food, and the time they're not eating the food really what the difference was. So, he designed an experiment uh which is really kind of cool. He designed experiment based on the rhesus monkey studies of the University of Wisconsin and the National Institutes of Aging. And these were calorie restricted monkeys, but only the University of Wisconsin studies showed extended longevity. The uh NIA study showed no extended longevity. And they had different diets. And he said, "I'll tell you what. I think you guys are both wrong. I bet you it's the time of eating." So, he designed an experiment where they had a calorie restricted group of both diets for rats. But he had a third group that that all their food came out at 3:00 in the afternoon. And animals ate it quite rapidly. And they still actually they ate up all their calories in about 8 to 12 hours and then they were fasting about 12 hours at least. That's a long time for a rat. They compared them to rats who got their food all day long and all night long. The rats who got food all day long all night had no metabolic flexibility. They couldn't make a change between burning sugar and burning fats. Right. The rats who got full calories but had it put out at 3:00 in the afternoon had metabolic flexibility. The rats who were calorie restricted also had metabolic flexibility. So, then they looked at longevity. The rats that had a full day's calories but ate at 3:00 in the afternoon lived 11% longer than the rats who got a full day's of calories that they ate all day and all night. Mhm. Now, for us that equates to a 10-year increase in lifespan. Now, is that on the same amount of calories? On the same amount of calories. That's crazy. Well, it's not so crazy because the Italian athlete study proves the point in humans. And what's that? This is a really cool study. They took Italian cyclists and they put them on a training table for 3 months. And most people know what a training table is. You guys, here it is. This is This is the food you're getting. And everybody had they ate the exact same food. The exact same amount of calories. All they did is change how often the guys got to eat. Mhm. One group, they got three meals a day. One group got breakfast at 8:00 in the morning, got lunch at 1:00 in the afternoon, had to finish dinner by 8:00 at night. A 12-hour eating window. Other group, same food, got breakfast at 1:00 in the afternoon, lunch at 4:00 in the afternoon, and had to finish dinner at 8:00 at night. Same amount of calories. Followed for 3 months. Same exercise program. The group that ate in a 12-hour window stayed the same weight. The group that ate in a 7-hour window lost weight. Lost significant amount of weight. But their performance was the same. Here's the best part, maybe the take-home message. You and I know there's probably our best method to predict longevity is a blood test called insulin-like growth factor one, IGF-1. Probably the best indicator of whether mTOR is activated or not. Um the guys who ate the 7-hour window, their IGF-1s plummeted. Mhm. The guys who ate the 12-hour window had no change in their IGF-1. So, the take-home message was it wasn't the calories the guys were eating. It was the time period that they were eating the calories. Now, why is that? Early on I mentioned that most of us, if we have metabolic flexibility, start making ketones about 8 hours after we stop eating. And by 12 hours, we've really started, you know, kicking up our ketones. So, those are the 12-hour guys. They're just kicking into ketone big time, and then they Right. stop the ketone production. The other guys, they're kicking into ketones, and then they're waiting another 5 hours to get their first bite of food. So, they're producing ketones 5 additional hours. So, they got 5 hours every day to uncouple their mitochondria before they go back and stop the process. So, it's the cycling in and out of getting the benefits of ketosis without full ketosis that makes all the difference. It's amazing. Okay, so now that we understand the mechanism, which at least for me is huge. Once I understand it, I don't know, there's something happens in my brain, I can really get behind it. Um give us a quick thumbnail sketch. Animal meat? Plant? Like, how should we be eating? What's What's that look like in a rough nutshell? Well, here's one of the big revelations for me. Um as you know, I I'm the only nutritionist that spent most of my career living in a blue zone, Loma Linda, California. Uh it's the only blue zone in the United States, by the way. Sad. And one of the things that shocked me when when I moved to Loma Linda was the amount of fat and particularly dairy fat in the Adventist diet. And I met with a nutritionist at the hospital. And because the the food in the hospital cafeteria and Adventists are vegetarians or vegans. About 36% of Adventists are vegetarians. About 5% are vegans. A number are pescatarians. But so great deal of the Adventists are vegetarians or at least pescatarians. Right. And yet 50% of their diet was dairy fat. From Whoa. yogurts 50%? 50% yogurts and cheeses. And I'm going, you you're killing, you know, my my patients. You know, I'm a heart surgeon. You know, I'm a cardiologist. You're killing my patients. They go, "No, we're not. We're the longest living people in the United States. You know, do your homework." I go, "You're You're killing our patients." So, as I was researching this book, I said, "You know, the Adventists eat a lot of cheese and dairy." Let's look at the other blue zones. So, you look at Sardinia, which is another blue zone. You look at the Nicoya Peninsula with in Costa Rica, which is another blue zone. You look like at Icaria, which is Greek island. And lo and behold, the Sardinians are unique in that the Sardinians are base basically two populations. There's the folks who live up in the mountain and the folks who live down by the sea. It turns out only the people who live up in the mountain have longevity. I see, that's interesting. And they're sheep herders and goat herders. And they eat huge amounts of goat and sheep cheese. The folks who live down by the sea don't aren't goat and sheep eaters and they don't eat goat and sheep cheese. So, there was a beautiful paper. We didn't put it in the book, but I'll tell you that showed that the difference was the fact that these guys were eating goat and sheep cheese. So, now you go, "Well, wait a minute. What's so cool about goat and sheep cheese?" Something in there that's uncoupling mitochondria? I have a hunch. got it. It turns out that 30% of the calories in goat and sheep milk are medium-chain triglycerides, MCTs. In fact, most of the MCT fats are named after the Latin word for goat, capra. There's capric acid, caprylic acid, uh goat. Because goat milk and sheep milk have tons of MCTs. And remember, MCTs are unique in that they go directly to the liver and generate ketones. So, these guys were generating ketones just by eating goat and sheep cheese. Let's jump to the Nicoya Peninsula. Now, a lot of bean eating and corn eating in Costa Rica and on the Nicoya Peninsula. But, what's so unique about the Nicoya Peninsula is that they're goat and sheep herders. And there's a beautiful paper that showed the difference is the goat and sheep cheese, not the beans and corn. But, calves don't do it for some reason. Nope, they don't make MCTs. Hm. Let's jump to Ikaria. Two factors in Ikaria. They're goat and sheep herders. They have yogurt every day. They have goat and sheep cheese every day. And they eat a weed, a common weed called purslane, as a major part of their diet. People see purslane growing in sidewalk cracks all the time. It's uh moss roses, portulaca, that people have in their gardens. They eat it as salads. It turns out that purslane has an amazing short-chain omega fat called alpha-linolenic acid that I profile in the book. Alpha-linolenic acid is magnificent for uncoupling mitochondria. So, it turns out that four of the five blue zones get their benefit by uncoupling mitochondria. And it turns out that the Okinawans 85% of the ancient Okinawan diet was a purple sweet potato. It wasn't rice. They don't do it. It wasn't soybeans. They only use miso. It was the purple sweet potato, which is full of the purple polyphenols and have any more? Now, the Okinawans are eating a Western diet. But so, all of these guys were uncoupling their mitochondria. All right. So, eating goat and sheep cheese, Yeah. purple Okinawan potatoes, and we're going to uncouple until the end of time. It basically, yeah. So, I mean, the great thing is you don't have to suffer eating an incredibly boring high-fat diet if you have goat and sheep cheese. My wife and I literally have goat or sheep cheese every night before dinner now. But you're plant-leaning, right? So, Yeah. But, you know, again, when I when we talk about eat the rainbow, and everybody talks about eating the rainbow, what we're actually saying is eat polyphenol-laden plants. That's literally what we're saying cuz the rainbow are those polyphenols. Right. And I go into the ancient spice trade from the Middle Ages. Yes, you do. And it turns out you look at those spices that people were ready to pay exorbitant amount of money for. In fact, you asked an interesting question in the book and you said, "Was this the original drug trade?" Yeah. And that's interesting cuz when you start to learn the history of like the spice wars, like people were killing people in like genocide levels for spices. and in fact, 50% of the people on these ocean voyages on for the spice trade died. Jesus. And so It had to be something pretty worthwhile. This was drug trade and they were the trade they were actually doing was for polyphenols. I mean, for instance, cinnamon was huge, cloves were huge. And I even have a fun chuckle, um the gift of the Magi uh in the Bible, uh two of the three gifts were actually frankincense and myrrh, which are polyphenols and both are shown to uncouple mitochondria. So interesting. They brought the little baby Jesus mitochondrial uncoupler. Yes, they did. Yes, they did. It's really incredible. Dr. Gundry, this is phenomenal. The book was really, really interesting. Thank you so much. Where can people get the book? Where can they follow along with you? Uh hopefully everywhere books are sold, amazon.com, barnesandnoble.com. Please go to your local bookseller. They need your help. The pandemic's been a disaster for them. They'll have the book. I've had multiple New York Times bestsellers. They stock my books and they'll stock this one. Um yeah. And then your 200th episode's coming up. 200th episode of the Dr. Gundry podcast is coming up. So wherever you get your podcast, we're on PodcastOne, the largest podcast carrier. Um Yeah. YouTube, that's where I take it in. Yeah, I got two YouTube channels. Find me on Instagram, please. Um find me at drgundry.com, find me at my supplement and food company, uh gundrymd.com. Hopefully find me. There it is. All right, guys, the book's incredible. I really feel like there's something interesting happening right now with a lot of these discoveries coming together around what's happening with mitochondria, insulin resistance in an advantageous way that goes awry in a Western diet, but it's really, really intriguing. I encourage you guys to dive into it. I think it will make it easier to implement the stuff in your life. Speaking of things you can implement in your life, if you haven't already, be sure to subscribe. And until next time, my friends, be legendary. Take care. Peace.