 It is true that there are many forces in nature, almost like developed instincts that we have that drive us to try to eat foods that will make us gain weight. All right, Dr. Johnson, it's great to see you. Welcome to the podcast. And thanks so much for coming on. I've been really looking forward to this. So have I. I've been following your work for a long time and it's really been enjoyable to read your insights. And now I have the opportunity to talk to you as well. So I'm very excited. Well, you know, that title. So if I used to be fat, so I would have loved your book because that title tells me nature wants me to be fat. So thank you so much for writing that book because now I can be fat. That's not what you mean, right? Well, that isn't what I mean. I'm not saying it's good to be fat. But it is true that there are many forces in nature, almost like developed instincts that we have that drive us to try to eat foods that will make us gain weight. So there's no doubt that we have harnessed nature's, you know, nature's loss into helping us go the wrong direction. And it's a pretty interesting story. So elaborate on that. I actually wrote about that. Let me, in my first book years ago, Dr. Gundry's Diet of Evolution, I talked about how great apes, and you and I are great apes. Sorta. Great apes only gain weight during fruit season. And my editors at Random House at the time said that's ridiculous. That's ridiculous. And this was in the early 2000s. And there's actually huge amount of literature published. Oh, absolutely. So go into that, would you? Well, yes. So just to answer, you know, to confirm you on this, orangutans are the ones that have been studied the most. And they will, during the fruit season, they will gorge on fruit. They will gorge on fruit. They don't eat one or two fruits like we do, which, and one or two fruits at a time is healthy, right? But when you eat large amounts of fruit, the fruit contains sugar. It's sweet. And that sugar is fruit dose, which is also in table sugar. And that happens to be the primary nutrient that activates a process to try to, you know, shift the energy that we produce from active energy that we use to stored energy that is fat. And so these orangutans will, you know, there was an anthropologist, Cheryl Knott, who did these studies. And she would, you know, watch the orangutans and collect a urine off the trees. And she showed that they actually, when they eat fruit, they basically go into a fat storage. They quit making any ketones or anything like that. And they go into a fat storage setting. And then they actually increase their fat storage, maybe by 20 percent. You know, they can get 15, 20 percent weight gain. And so they really become a little bit plump and portly, you might say. And then during the rest of the season, where they're having to leaves and twigs and very few fruits, they actually live off their fat during those part of the year. And there are other primates that do it too. There's a lemur, fat tail lemur, who will eat a lot of fruit during the wet season. And then during the dry season, they'll actually hibernate. You know, it's not hibernation in the summer. It's actually estivation. But for all purposes, it's hibernation. They go into a hollow tree. And then they basically drop their metabolism and live off their fat. And they use their fat not just for energy, but also to make water. Because during the dry season, there's not a lot of water. And when you burn fat, you produce water. So burning fat not only produces energy, but produces water. And some animals use fat as a way to give them water during times when there's not. So yeah, there are these primates that eat a lot of fruit. And there's an evolutionary story there. And the big part of our story was the discovery that animals want to avoid starvation. There's nothing worse. There's four great things that animals do not want at all costs. One is they don't want to starve. Starvation's bad. It leads to death. Dehydration's another one. No animal likes to be really severely dehydrated. No animal wants to run out of oxygen if it's like in a burrow. And there's not enough oxygen that no animal wants that. And no animal wants a predator. And so there's this, you know, so that we've learned, you know, in biology, we've learned the responses that animals do to these, you know, these things. But what we, you know, obviously an animal would prefer to avoid it. You know, like the old ant and the grasshopper would be nice to you know, prepare for a winter and have that food stored away rather than be the grasshopper. And suddenly it's winter and there's no food and you're going to starve. So what's happened is that there is a absolutely incredible finding that certain foods, when you eat them, actually are preparing you for a period of time when there's no food around. And this is when animals eat these foods, they activate an actual biologic switch that allows them to store fat. But it doesn't just store fat. It does a host of responses that are aimed at protecting it. And so we've actually developed tastes for these foods. And so we have an instinctual desire to eat foods that can actually help store fat for us. It was all aimed as a survival mechanism way back when food wasn't always on the table. The grocery stores weren't chock full of food. And so it's a biologic response. That's why nature wants this to be fat because there are these foods that actually trigger a biologic response to store fat. Well, all right. You've wet my appetite, so to speak. What are those foods that you know are going to activate this fat storing switch? So when we were looking at this, we realized that a lot of animals will eat fruit. And you just talked about this, not only the orangutan, but things, animals that hibernate like bears. You know, in the fall, the fruit starts to ripen. And that means it gets sweeter. And it's almost like a link with nature, because when the fruits ripen, the seeds also mature. And so that when the fruit is eaten by the animal, the fruit actually, the seeds can disperse and then be used, you know, to plant and, I mean, to grow a new fruit tree. So fruit trees seem to know in nature that if they make the fruit ripe, that's going to increase its ability to survive because more animals will eat it and then disperse the seeds. So the fruit, as the fruit ripens in the fall, the animals know, have learned that this actually helps them gain fat. And or whether or not they've learned it, it's now part of the nature's response. It happens. So they start eating the fruit. And it's been shown like for birds that are going to migrate long distances, they have to store fat to travel thousands of miles, they go nonstop and animals that nest. And there's even fruit, a fish that eat fruit. And so it turns out that fruit seems to be used when it's eaten in excess to help animals gain weight. So we were studying this and we realized that fruits, you know, we consider them very healthy. But when you eat huge amounts, it seems to trigger a switch. And the main nutrient in fruit is fructose, which is a sugar, which is also in table sugar and high fructose corn syrup. And it's basically the main way we get fructose is from these added sugars, table sugar and high fructose corn syrup. It makes up the vast majority of sugar people are eating or fructose that people are eating. And so what happened was we said, okay, we're going to give fructose to an animal. And when we did it, they, you know, normally animals will keep, regulate their weight really well. And they, you know, if they eat more one day, they eat less the next, if they exercise more one day, they exercise, you know, they rest the next day, you know, and animals generally speaking in the wild try to maintain a regular weight because they don't want to get fat, get eaten by predators and they don't want to, you know, so they normally regulate their weight. But if an animal is preparing for hibernation, they start eating this a lot of fruit, then suddenly what happens is it loses that ability to regulate its weight. They become hungry all the time. They become thirsty. They start foraging for food. This is all part of the biological response. So they, they, they actually decreased their willpower because they, they have to have the strength to go into areas that they've never been to that are maybe dangerous. So they don't want to, they, they, they, when they go in there, they have to look around rapidly and they can't deliberate. They can't, you know, they, they basically, they have to reduce their recent memory a little bit because they don't want to remember the predator that, that might be in that area too vividly. So they, they want to kind of dampen the memory. And so what they do is that they actually reduce certain area of activity in the brain that allows them to forage and they, they actually become on, they actually start increasing their foraging behavior. And they, they, not only are they hungry, normally animals regulate their weight, as I mentioned. And in the first couple of weeks where you're eating a lot of fruit dose, if you, if you give it to animals, they do regulate their weight. So although they'll, you can put fruit dose in the drinking water, they'll eat, they'll drink a lot of the water because it tastes real good, but initially they'll reduce their chow intake so that they don't gain weight. But after about two weeks, two or three weeks, suddenly they lose that ability to control their appetite and they keep eating and they, they start eating more chow, even though they're drinking all this fruit dose. So what happens is that their total energy intake goes up. And so they're eating more and more calories, their food intake's going up. And although they're foraging, when they're not foraging, they reduce their metabolism. So they become like couch potatoes. So their, their resting energy metabolism drops, but their, but their, their, their ability to, when they're foraging is maintained. So it's like this really cool system where they're trying to conserve their energy, use it for when they need it. They use, you know, and, and so, and they become insulin resistant. And insulin resistance helps reduce their energy metabolism because, you know, it reduces the glucose taken up in the muscle. So there's less energy being spent in the muscle. So that reduces the, the requirements so that you can live off a lower level of energy. So, and then they, they do this and phenomenal thing where they, they work on those in the mito bar. They go in there and they suppress activity. It's just a general suppression of activity. And, and, and so what happens is they do it by inducing oxidative stress, not, not just the, from the mitochondria, but they actually engage in another enzyme called NADPH oxidase. No one wants to hear that. But anyway, they cause stress to the mitochondria, reduce the energy, the general amount of energy being produced. And they, and what happens is the calories then get shunted over to fat, which is the stored energy. So instead of making ATP, the energy from food is, is shunted, is transferred over to make fat. And so it's this beautiful thing where they, where it's a great way to store fat. So the animal, what's incredible is the animal starts storing fat, even though they're not, you know, they're not in a starvation state. They're, they're, they're not starving, but, but it's preparing for starvation. So it's helping you store fat so that when that event comes, you, you have the enough fat to survive through that period. So it's a, it's an amazing set of responses. And we call it the metabolic syndrome. We call it, hey, you know, this, this is abnormal. This is pathologic. We shouldn't, you know, insulin resistance leads to diabetes and, and it also like it raises blood pressure a little bit. And that can lead to hypertension. And so we think of it as, as bad. And it is bad for us, because it, when you keep activating the switch, it does shift from insulin resistance to diabetes. And it does move from elevated blood pressure to hypertension. And it does move from temporary fat stories to help you during periods of stress to, to suddenly it continuing, the fat continues to grow. And so the problem is, is continued activation of the switch. And we're doing it because we're not just eating fruit, a lot of fruit in the fall when, when the trees are, you know, when the fruit's ripening, we go to the store and we can eat sugar all year round. And, and, you know, we've, we developed it, you know, we have a taste for sweet and we have a taste for this. And so, so we pick out these foods and, and, you know, that taste is actually, you know, was what developed, we think, to, to so that you couldn't find these foods. And, you know, in the days when things were, were, were tougher, you know, this was, it was an advantage to be able to find those foods that are sweet and that contain fruit does. So what you mentioned that most animals, they'll do fine for about two weeks. And then they suddenly shift over to this fat storage. What, what's taking place? Is it the insulin resistance that drives it? Or what do your studies show? Yes. So, so it turns out that there's, you know, as you know, there's this hormone leptin. And leptin is produced by the fat. And normally people, you know, leptin is the hormone that it's linked with insulin, just as you say. But when you eat, leptin communicates to the brain when, when you've eaten enough. And so leptin is the hormone that tells you you're full. But it's been known for a long time that people who are overweight don't are resistant to leptin. The leptin levels go up, but they'll still eat. You can, if you have an animal that's leptin resistant, you can prove it, you know, by injecting leptin. So if you, and then monitoring how much food they eat. So, you know, normally an animal is eating food, and if I inject it with leptin, it's going to reduce its food intake immediately. Within 24 hours, the food intake is down. But if an animal has what we call leptin resistance, they'll keep eating. And if I inject it with leptin, it still keeps eating. It doesn't change. And what we found was that fructose causes leptin resistance. But it takes several weeks. And we even did a, we did a whole series of studies on this, you know, is they're sort of really interesting. So if you take an animal and you give it fructose until it becomes leptin resistant, you can take the sugar away. And, and, but it will continue to eat more calories than it wants for at least two to three weeks. So that leptin resistance will persist when you stop fructose. And here's a really interesting thing. Fructose itself, you know, it does cause, you know, it will lead to weight gain just by itself, but it's not, it's not huge. What really causes the weight gain is the eating a high fat diet with fructose. So the fructose makes you leptin resistant. But then the fat really accelerates the weight gain because it's so energy dense. So it turns out that weight gain, when we did studies, like we've done all these very careful studies, what drives weight gain is this combination of leptin resistance plus too many calories, you know, food. If you, if you make an animal leptin resistant, but you don't give it extra food, it will gain a tiny bit away from the drop in resting energy metabolism. But basically, it will not gain much weight. And, but if you give, and so if you do like isocalloric diets, like the sugar industry will do studies where they, we do, they put everyone on the same number of calories, and then they say, well, sugar doesn't cause weight gain. And the answer is yes, sugar doesn't cause weight gain when it's isocalloric. The way sugar causes weight gain is that the fructose makes you want to eat more. And then when you eat more, that's what causes the weight gain. But what's interesting, Steve, is that if you give sugar and make it isocalloric or even a hypochloric, where they're on a diet, in other words, if you, if I put you on a caloric restriction, but your diet is really high in sugar, you're not going to gain weight because you're on a caloric restriction. But you're going to, you could still get diabetes and you could still get fatty liver and you still could get hypertension. When we did it to animals, we found that we could induce diabetes, high blood pressure, out fatty liver, even on a diet where the animals are eating less than they normally eat, provided they're eating a high fructose diet. So the fructose is working two ways. It's working through, you know, through an energy, classic energy balance story, where it's making you eat more and that's driving weight gain. But it also has a direct metabolic effect that is independent of excess calories. And that's what's driving diabetes and all those things. And so it's sort of interesting that it unites the two major, two of the major theories out there, the energy balance, people who say everything is just calories. And also the low carb people who point out how low carb diets are so much better in so many ways. And so it does kind of unite those. Yeah, you know, there's, I guess there's a fairly popular book suggesting that diabetes can be cured by, by a fruit diet, that you should just eat massive amounts of fruit and you'll cure diabetes. And I've, and these, this has not been written by physicians, by the way, but by PhDs, and that's okay. But I have had several of my diabetic patients read this book and try it. And what you observed is what I observed is that this is one of the best ways to cause diabetes, worsen the hemoglobin A1c, exactly because of the mechanisms you mentioned. Any thoughts on that? Yeah, no, I agree with you. So the fruit story is an important story to understand because the, the natural, you know, as you know, as you're like a world expert on, fruits contain a lot of polyphenols and really wonderful compounds that, that block fruit dose. So natural fruits like can have vitamin C. I'm actually a fan of vitamin C. We've done some work on it. We can show that it blocks fruit dose effects to some extent. You know, it contains epichatechin and quercetin and all these wonderful flavonols that can also block fruit dose effects. It has lots of fiber and it has potassium. And so in general, small amounts of fruit are great because you get all these flavonols and vitamin C and fiber. And I'm a big fan of, of natural fruit and small amounts. And also the, a natural fruit may have four or five grams of fruit dose. Some of them, like an apple, may have a little bit more. You know, when you get up around eight to 10 grams, they start getting a little nervous. But, but, you know, definitely in that four, a lot of fruits are in the four, three to six gram range. And, and my friend, Joshua Benowitz, who's a doctor at Princeton has done this really wonderful work. And he's shown that, you know, the first three or four grams of fruit dose that you eat get inactivated in the intestine. And so it's the fruit dose that gets to the liver that's the problem. And so when you just eat one or two fruit, a lot of that fruit dose is not, is being inactivated. You're getting relatively little to the liver and yet you're getting all these other good things. But if you, now if you take the fruit and you say, okay, I'm going to make fruit, I'm going to make smoothies, and I'm going to take 10 fruit and I'm going to drink this juice in 30 seconds. And now you're getting this large amount of fruit dose because you're combining it with all the fruit and you're, you're drinking it really fast. So it's going to overwhelm the intestines, going to get to the liver. And now, and there's not, you've taken out the pulp and the fiber and a lot of the good things. And now you're going to get it, you know. So I've had, just like you, I had patients come to see me where they were having trouble losing weight. And it turns out they're eating, drinking fruit smoothies after every run and all these things. And you can overdo the fruit. Now, having said that, you know, fruit smoothies are bad and fruit drinks are bad and fruit juice, you should be very careful with, you know, having said all that, you know, we did do a study in which we put overweight adults on a low sugar diet. And one group also had to eliminate fruits. And the other group got to add back fruits so that they could eat a certain number of fruits. And it turned out that adding back fruits did not block the ability of the low sugar diet to work. So we had success in the patients losing weight, improving their metabolic syndrome. But adding back some fruits, you know. So I think that one or two fruit with a meal is probably very good. It has a lot of good things. But if you're eating large amounts of fruit, if you're eating that bowl of grapes that while you're watching TV, or you're, you know, so I agree with you on every set. Yeah, you know, I used to tell my patients, look, let's go down to the San Diego Zoo and look in all the cages. Nobody's got a juicer. We've just manipulated ways to, you know, mainline of fructose. Exactly. And the other thing is, you know, we never had 747s bringing fruit from Chile and Argentina to Colorado in February. And, you know, I grew up in Nebraska and there's no fruit in Nebraska in the winter. And we did not have access to these things. Yeah, so all this, all this is important. You know, we did, we also, another aspect of fruit juice, why I don't like it is we did a study with apple juice. And apple juice is but a sweetest soft drink. So it has as much fructose as a soft drink. And we knew that the, so the way the fructose works is it's not working through its calories so much as it's working by dropping the energy in the cells. Where I mentioned it causes the mitle bar. It reduces the energy produced in the mitle bar. Yeah. And the amount of ATP coming out is reduced. And it shifts it to an archaic ancient system called glycolysis where, you know, that makes just small amounts of ATP. So ATP levels fall on the cell, which when you, when you have fructose. So fructose can decrease the energy in the cell. And that is how the fructose activates this big switch. It's not from the calories. It's from this unique ability of it to reduce the energy in the cell. And so, so that's a very important point. So what we did is we realized that if we gave apple juice to people, that if we gave the apple juice in a large amount over a short period of time, that it would drop the energy in the cell very rapidly because the concentration of fructose that hits the liver would be high because it's both the amount and the speed that makes up the concentration. Whereas if we gave the same amount of apple juice but gave it over like an hour and a half delayed how long we gave it, that it would kind of trickle in and it wouldn't have the same effect to activate the switch. So in other words, how you eat your food could make a difference. And what we found was it was exactly true. If you drank it and you drank it fast, you could really activate this biologic switch to gain fat. Whereas if you could drag it out over a long period of time, it was like a calorie. It lost its ability to activate the switch. And so it really relates to that. The kid who drinks that guzzles down the soft drink when they're thirsty out on the heat. They're activating the switch big time that way. And that's why liquid sugars are so dangerous because we tend to drink soft drinks and power drinks and energy drinks. We tend to drink them fast. And adding sugars to coffee and tea is not good when you add sugar to it. I went to this place in eastern Russia, I mean, I'm sorry, western China, right on the edge. And it was a remote area where the Chinese actually look like Russian people. It's really interesting. They're speaking Chinese, they're part of China, but they're actually not your typical Chinese. And these people would drink this tea. Steve, I saw this guy come in and he was very overweight and he pulled out a little bag of sugar. And he put like three bags of sugar, little tiny bags, into one cup of tea. I mean, I shouldn't have been staring. That was kind of rude of me, but I couldn't believe it. It was like half of the tea was sugar. Half of that, you know, it was like this, how could you drink that? And the poor guy was very, very overweight. But it turned out that that was the custom in that little town to have a lot of sugar in your tea. But anyway, so I'm sorry I digress, but anyway. Well, that's like our custom of having a Frappuccino. Exactly. And we wonder why. Well, so you brought up an interesting point. Where's your take on a calorie is a calorie is a calorie, and it's calories in and calories out. I know your take, but tell everybody else. Yes. Well, it isn't that simple. I wish it were. When it comes to calorie, calories are what primarily drive weight gain. So it is true. Calories are primarily what drive weight gain. But why you eat more calories is because you've you get left in resistance and and that you're getting from sugar. We actually did studies. If you give fat to an animal, it will not develop left in resistance. You give sugar to an animal at will. And it's the sugar that triggers, that really makes an animal want to eat more. So, but the the fructose in sugar is also what drives all the metabolic effects like pre diabetes, like fatty liver, like elevated fats in your blood, like high blood pressure. And those are driven independently of excess calories that can occur on low calorie calories, if you're eating a lot of fructose. And so so it's it's a little bit of both. But in general, I would say that is it's more important food selection is more important in in the treatment in treating and trying to get to weight loss. And I think your idea of, you know, developing healthy ketosis and mitochondrial and coupling. And this is a wonderful way to lose weight. And equally important probably is to avoid eating foods that make you want to eat more calories. So you you and coupling is a great way to burn those calories you're you're eating in excess and really helping you lose weight. But if we can also and you're you of course recommend pretty much a lot a lot of along the same lines of what I love what we discovered with our research. But you know, sugar and fructose are one of the key drivers that that activate the switch to gain weight. And and what really expanded our story. And we we need to go there is this discovery that it isn't just the fructose we eat. That's the problem. It's the fructose that we can make. And our body can make fructose and it does it only one way. And it does it from make it makes it from glucose. And when when there's too much glucose around the, you know, the body starts converting that to fructose. And this is the problem of high carb diets that are just rich in in starch and these these foods like white flour, bread, rice, potatoes, cereals, chips, potato chips. And these these are starchy foods that release a lot of glucose. And so the body senses that extra glucose. And not only does it stimulate insulin to help move that glucose into the tissues. But what it's doing is it starts to convert some of that glucose to fructose. And when that happens, the fructose activates the switch makes you hungry makes you want to keep eating makes you forge makes you do all all the things that regular fructose does from the diet. You can get it from when you make fructose. And we we had these animals that cannot metabolize fructose, they stay skinny all their life. They're really an amazing animal, they don't get fat, they don't get hypertension, they're protected from fatty liver. You you know, it is possible to make them fat with butter fat. And we can talk about that. But it's a very healthy fat in this. Well, it's not healthy fat, but they don't have fatty liver and they don't get diabetic and so forth. But anyway, with these animals, we were able to show that if you feed glucose, you can also block the, you know, the glucose gets converted to fructose, and these animals are protected from obesity. But I can make animals get obesity and activate the switch just from things like bread and rice and glucose. So it turns out that there's two, you know, it's not just the fructose we eat, but but certain carbs, not all carbs. There's a lot of great carbs, a lot of great plant carbs, you know, but there are a lot of carbs that are good, but the carbs that are really starchy, that increase the glucose levels in our blood, they get converted to fructose and they're just as bad as sugar. So if you're eating a lot of white bread and rice and potatoes here, you're, you're, you can get into trouble. And so that was the kind of a big discovery. And then we discovered that there were other foods that could activate the switch, too. I don't know if you want me to go into all those. Yeah, let's go into that. Although I want to stop you for a second because you're right, I have a number of people that swear that they do not eat any sugar. And yet, you know, their insulin resistance, their overweight, and then we start looking at their diet and it's a very high starch diet. And sometimes they're quote, you know, good starches like sweet potatoes or and when we take those starches away from them, that's when things, you know, start turning around for these individuals. So your observation is great that we, just by eating a lot of glucose, which is starch, you know, combined with lots of glucoses, you can convert fructose and flip the switch. That's a great observation. Yes, it was, it was really exciting because, you know, originally I had thought it was just the fructose we eat. And I was on a podcast with Jimmy low carb Levita or whatever, you know, you I think you know, Jimmy. Yeah, Jimmy Moore, wonderful person. And, and I was talking about low fructose diets. And he says, Doc, he says, you know, I tried to cut out sugar. And I had a lot of people who responded to my diet, you know, this was my first book way back when 2008. And he says, you know, I had a lot of people, you know, you know, I tried to cut out sugar doc, but I found that I had to cut out all carbs to really for it to really work. And I, and now I know why, because it isn't that you need to reduce all carbs, it's just you need to reduce the bad carbs. And these high glycemic carbs, which we call, you know, like starching foods, they can activate the switch as well. Now we had another discovery. So once I knew that the body could make fructose, I started studying the this, you know, what regulates that. And it turns out that it's turned on by low oxygen states by low, low blood flow, you know, all the things that those first four things I told you that animals try to avoid like low oxygen, you know, nutrient, low, like ischemia, you can actually activate when you have a, if you have a heart attack, your heart will start making fructose. And there's, you know, papers in nature showing that when that happens, the fructose is meant to be a to help. But what happens is it's just, in humans, the reaction is just so over too much. And it actually can cause cardiac disease. And in the kidney, it can cause problems. And in the brain, it can cause problems. But so it turns out that this fructose can be produced in the body whenever there's stressful situations that kind of threaten make the organ feel threatened. Then it starts to be produced. And if it's produced too much, it's a problem. So that was one thing. But the other thing was I was thinking about diet. And I realized that what really stimulates this reaction to convert glucose to fructose is what is anything that raises the salt concentrations in the blood. And what we call, I mean, it's, it's basically everybody has a serum sodium that they get on their blood test. And we all ignore it, you know, unless it's, you know, doctors, typically it's normal and, you know, you don't normally get people don't normally call you and say, you know, your sodium is on the upper left end of normal. But it turns out that the sodium concentration can control this reaction. And people who have a higher sodium concentration, because they're not drinking enough water so that the salt concentrations higher in their blood. People who don't drink a lot of water will have a higher serum sodium and they'll have a higher risk for obesity. And if they have a lower serum sodium, even in the normal range, they'll be more likely to be skinny. And these data have now been published. We've actually looked at it as well. And, you know, it's phenomenal that that the sodium concentration, which is governed a little bit by the, how much salt and water we're having. So when I, when I eat salt, if I eat salty food, the salt concentration goes up and it helps convert the glucose in my body to fructose. And that's why the French fry is so bad. That's why potato chips are so bad because the salt actually stimulates the conversion of the glucose to the fructose. Oh man. So you mean, I can't put some Himalayan salt on my raw pistachios anymore to make them really tasty? I think you can, but there's a trick. So let me tell you the trick. I did this study. So I gave people salty soup. I did this. I mean, I say, I, I'm a co-author, but it was done in Turkey by my colleague, Mehmet Candy. So we wanted to see the power of salt. So what we did is we gave soup and you can mask the amount of salt and soup. So, you know, we added the salt to me. The soup was quite salty. And when they, not super salty, but, you know, when the people drank the bowl of soup, the salt concentration, we could measure it in their blood, goes up within minutes, and it just went up. It stayed in the normal range. It just went up like two points. So it went like from 138 to 140, you know, still in the normal range. But when it did that, it activated the switch. We could show that with special blood tests and also the blood pressure went up. So the salt was activating the switch, right? And, but then we gave one group. This was all done blinded. One group got water with it. And so they had to drink this water. And when they drank the water, even though they had the soup, now they prevented that salt concentration from going up because they neutralized it with the water. And the, and the switch wasn't turned on. And so this tells me that the next time we go into a bar, not the metal bar, but a regular bar, if you want to eat those pretzels, if you want to eat those chips, it's okay. But what you want to do is drink water before to drop the serum sodium. You don't want to get, as soon as you feel thirsty, you've activated the switch, basically. So if you, if you eat enough salt that you're thirsty, you've, you're activating the switch. So stay well hydrated. So we even did a study with animals where we gave them sugar and food. And believe it or not, when you give sugar, it also increases the salt concentration of the blood. It's sort of interesting that moves, moves the water into the cell and makes the water concentration or the salt concentration of the blood go up. So even soft drinks, they're dehydrating. We all knew this, you know, everyone knows that if you drink a soft drink, it does not hydrate you well. In fact, your serum sodium, yeah, it makes you thirsty and your serum sodium goes up. It's exactly right. And it activates that, it's activating that process to make more fructose from the food you're drinking from the soft drink. So it, you know, so if you drink, we gave soft drinks to animals on regular diet, just regular chow or on Western diet, and we could really increase their weight gain through this salt mechanism. Actually, we also just did studies where we increased salt. We gave animals just a high salt diet. And it takes a longer time than with sugar. It takes like three or four months instead of three or four weeks. But suddenly, the animals became hugely fat. And if we gave them water, we could suppress the development of obesity. We could give them extra water. And we did that by putting water in the, in the chow. We injected water into the chow. And by doing that, they ate the same amount of chow. Actually, they started controlling their chow intake. So they're eating less chow because they became more leptin sensitive. But anyway, what happened is we could, we could treat obesity just by increasing water intake. All right. Since we're talking about fructose, let's talk about uric acid. Oh, yes. So what, so what's the deal with uric acid? A lot of people think about uric acid, they heard about it with gout. Some people have heard about it with high blood pressure, kidney issues, one of your specialties. How, how is all this tied in? Okay. So, so uric acid is a substance that's, you know, got a lot of nitrogen and it's basically a breakdown product. It's that we have in our blood and it's, it's broken down from the DNA, from the nuclear material in our, in the, in the food we eat. So when we're eating protein and carbs and fat, we're also eating, you know, the nuclei of the, of the plant or the, you know, the, the thing that carries the DNA and RNA. And when those things get broken down in our body, they're converted to uric acid. And so we all, all of us have uric acid in our blood. Okay. And then we excrete it primarily through the intestines and the kidneys. And so normally, we have a low, a relatively low level of uric acid. It's actually higher than most other animals, but for us that, you know, it, and it doesn't bother us. So we have this substance in our blood. No one really cared about it, right? Because it's not a problem unless the levels get high. But if we're eating foods that can produce uric acid, then the uric acid can go up in our blood. And one of the foods that does that is sugar. So fructose, when fructose is metabolized, there's, there's basically fructose is broken down to carbon dioxide in water. So fructose is like a sugar, it's broken down. But there's this side reaction that occurs where fructose causes the ATP levels to fall. Remember the energy levels. And when that energy level falls, uric acid is generated. And the uric acid actually helps maintain the energy level at a low state. Because the uric acid actually is what is responsible for stunning the mitochondria, stunning the energy factories to keep the energy levels low. And so the uric acid that's produced actually has a biologic role inside the cell to kind of keep the energy level low. And that is associated with this activation of the switch. So we actually, to our surprise many years ago, when we were studying fructose, we found that the uric acid in the fructose was what was responsible for driving the switch. And, and so it, and so that the switch is not driven by the calories of fructose, it's driven by the side chain reaction. So what's happened is we've discovered that foods that raise uric acid also can, can cause obesity. So, so right now we have, think about, we have five tastes. We have the sweet taste, which is there to help us find fructose. And we have the salt taste, that's to help us find salty foods, which will help us make fructose. Then we have bitter and sour, which are these tastes to help us avoid eating foods, because they might contain toxins and so forth. And then there's a fifth taste called the savory taste or the umami taste. And this is the food taste that many of us love. It's like the taste for Caesar salads. And beer, for example, has this savory flavor, umami flavor from the yeast that's in the, in the beer. And, you know, there's a lot of foods that we, we like, the rich meaty extracts, you know, where you kind of simmer and you get that rich sauce. And, and it's been shown that what umami is, is it's actually consists of two things. It consists of glutamate, which is an amino acid. And it also consists of a breakdown product from, of these RNA and ATP. It's, you know, breakdown products, which are part of this pathway that activate the switch. And what we found sadly was that these umami flavors actually also activate the switch and, and they even glutamate gets converted to uric acid partly of it, part of it is. And so what happens is they can activate the switch. Now the good goes, Steve, is that by far the biggest thing that's driving the switch is sugar intake. It's we're eating 75 grams of that a day. Salt, we're eating maybe seven grams of salt a day, eight grams. And that is obviously helping to drive the switch. And umami, we're eating only like two to four grams of glutamate in a day. We're not eating, so we're eating much, much less. So it's much, much less important in that sense. But umami becomes a problem. And like certain rich meaty foods, proteins, especially, you know, like organ meats, liver, they're very high in umami. So plant proteins have much less of the, of the umami than animal proteins. And so plant proteins are superior in some respects. And the animal proteins, um, it also varies. So like processed red meats have a lot more umami than just regular red meat. And um, but, but it's true this puts a slightly negative light on super high protein diets, because high protein diets can contain a fair amount of umami. So um, and the umami can activate this switch. Now interestingly, the main way the switch is working is by the conversion of glucose to fructose. So if you're on a low carb diet, you're not getting a lot of glucose or fructose. And so even if you want to convert the glucose to fructose, if you're on an extreme low carb diet, there's not a lot of glucose around and there's not a lot of fructose around. And so a low carb diet will is a very good diet into the sense that it helps to protect. And of course you've brought up the benefits of ketosis as well for energy burning. So so I'm going to have to let you go and wrap up. What did you learn after writing this book that you can share with our readers? Anything? What happened? Well, soft drinks and any kind of liquid sugar is absolutely something to avoid. Um, you know, most of the time I would tell you that, you know, you it's not that you can't have cake on your birthday or things like that. But when it comes to soft drinks and liquid sugar, it's really wise to try to avoid it because it is by far the easiest way to activate this switch. So the second thing is the power of of salt and water. We know so many diets don't talk about this enough. And what we've learned is that when you're eating a lot of salt in it and the and if you're you feel get thirsty from it that you could be activating the switch. And so trying to cut back on salt and drinking more water and I recommend a glass of water with each meal and a glass of water between meals. Don't have to drink gallons of water. I'm not telling you that. In fact, it's dangerous to drink huge amounts of water, but a glass of water with each meal, glass of water between meals, glass of water at bedtime. You know, this will have a big impact and a nice additional impact on your health in so many ways. And then, you know, you know, high glycemic carbs like bread, rice, potatoes, really try to cut those back, things like sweets and stuff, try to save them for special occasions. I love intermittent fasting. We didn't talk about that. But time restricted fasting is a great move for all the benefits that you've written about. And and basically, exercise, we haven't talked about that. But, you know, it's important to exercise. They're good. It's good to help heal the mitochondria, these energy factories. And over time, these energy factories do get damaged. And so it's really important to try to help help them recover with with the techniques that you've proposed and exercise and all these all these things. So that's my main message, Steve. Make sure to check out the next one here. If you look at blue zones, if you look at other areas with super old people, one of the things that jumps out at you is they're not gym rats. They're not spending time in the gym.