Dhru Purohit Show - #252: The Latest Science on How to Turn Your Body’s Fat Storage Switch Off with Dr. Richard Johnson

Episode Date: December 16, 2021

This episode is brought to you by InsideTracker. Why do we get fat? As Americans have gotten heavier over the past century, and disease rates have skyrocketed, there have been many theories: We’re eating too much fat. Too many carbs. An excess of sugar. Is it our lifestyle or our diet that’s to blame? Or could there be a single common cause that explains the sharp increase in not only obesity, but conditions as disparate as heart disease, cancer, and dementia?  This week on The Dhru Purohit Podcast, Dhru sat down with Dr. Richard Johnson to talk about his team’s discovery of the fructose-powered survival switch—a metabolic pathway that animals in nature turn on and off as needed, but that our modern diet has permanently fixed in the on position, becoming a fat switch—and how it has revolutionized the way we think about why we gain weight.  Dr. Richard Johnson is a Professor of Medicine at the University of Colorado in Denver and has been a practicing physician and clinical scientist for over 25 years. He is internationally recognized for his seminal work on the role of sugar and its component fructose, in obesity and diabetes. His work has also suggested a fundamental role for uric acid (which is generated during fructose metabolism) in metabolic syndrome. His new book is entitled Nature Wants Us to Be Fat and will be published on February 8, 2022. In this episode, we dive into:  -Why nature wants us to get fat and why it’s important for survival (5:44) -What triggers the fat storage switch (9:05) -The central function of uric acid in the body (16:32) -How uric acid, previously thought of only in terms of gout, is actually playing a central role in metabolic disorders (20:54) -Understanding the difference between fructose and glucose (26:12) -Why obesity is not a calories in, calories out problem (29:38) -Why it’s fructose (not glucose) that drives insulin resistance and metabolic disease (49:51) -The survival switch: why humans become fat (1:10:38) -Alcohol consumption and obesity (1:33:54)  -The surprising role salt and dehydration play in fat accumulation (1:48:45)  Also mentioned in this episode: -Nature Wants Us to Be Fat: The Surprising Science Behind Why We Gain Weight and How We Can Prevent—and Reverse—It - https://benbellabooks.com/shop/nature-wants-us-to-be-fat/. For more on Dhru Purohit, follow him on Instagram @dhrupurohit, and on YouTube @dhrupurohit. You can also text Dhru at [phone]. This episode is brought to you by InsideTracker. InsideTracker looks at everything from metabolic and inflammatory markers to nutrients and hormones. Traditional lab tests can be hard to read on your own, but InsideTracker makes their results easy to understand and provides tips on how to use food first for optimal nutrition. Right now, they’re offering my podcast community 25% off. Just go to insidetracker.com/DHRU. Hosted on Acast. See acast.com/privacy for more information. Learn more about your ad choices. Visit megaphone.fm/adchoices

So there's two major foods that are driving obesity. One is sugar and fructose generation from high glycemic carbs. And the other is salt, which creates dehydration. And that also stimulates fructose production and drives fat. Hi, everyone. Drew Brode here. Did you know that nature actually designed us to get fat? It's part of a survival mechanism.

and it was a big part of our evolutionary history. But now that survival mechanism has gotten out of control. And Dr. Rick Johnson, who's the world's foremost expert in this area with over 700 publications written on this topic, is going to teach us how to break out of it. So if you want to learn about the science of why we get fat and why nature wanted us to be fat, but how it's gotten out of control, this episode is for you.

Have you ever gone to your doctor for your normal annual physical? And after sitting with them for 10 minutes, they quickly look at your labs and tell you, hey, everything looks normal. Keep it up and I'll see you again next year. Maybe even give you a nice little pat on the back. I can't tell you how many listeners of the podcast have told me that they've had this exact experience and how honestly how frustrating it can be. Now, we all know that normal isn't always optimal.

Just because something's not wrong doesn't mean that we feel great. So traditional medicine is great at finding out when something is blatantly wrong. But they don't always do the best job when we need to highlight how we can do better. So what if you could get detailed nutritional and lifestyle guidance based on your individual needs? That's what Inside Tracker does. Inside Tracker was founded in 2009 by top scientists from acclaimed universities in the field of aging, genetics, and biometrics. Its mission is to help people live long, healthy, productive lives by optimizing their bodies from the inside out.

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to top nutrients and hormones. It even tests your cholesterol levels to help you better manage stress, and you have the option to see how your inner age compares to your chronological age. Traditional lab tests, can be hard to read on your own, but Inside Tracker makes their results easy to understand and even provides tips on how to use food first for optimal nutrition. Right now, InsideTracker is

offering my podcast community 25% off their system. Just go to insidetracker.com slash drew. That's D-H-R-U to get your discount code and try it out for yourself. That's InsideTracker. That's Inside Tracker, I-N-S-I-D-E, tracker, T-R-A-C-K-E-R-D-R-D-R-K-R-com, backslash-D-H-R-U for your 25% off. Welcome to the Drew Prod podcast. Each week we explore the inner workings of the brain and the body with one of the brightest minds and wellness, medicine, and mindset. This week's guest is Dr. Richard Johnson. Dr. Johnson is a professor of medicine at the University of Colorado in Denver, and he's been a practicing physician and clinical scientist for over 25 years now.

He's internationally recognized for his seminal work in the role of sugar and its key component of fructose in obesity, metabolic health, and diabetes. His work has also been suggested as a fundamental role for uric acid, which is generated during the fructose metabolism process in metabolic syndrome. Dr. Johnson is a prolific scientist with research that has been funded by the National Institute of Health since 1980. He's a member of the American Society of Clinical Investigation and has published over 700 papers lectured in over 45 countries and is highly cited. His first two books were The Sugar Fix and the Fat Switch and his upcoming book,

which is guaranteed to be a fantastic read for our podcast audience, is called Nature Wants Us to Be Fat. If you've been following my work in the space of metabolic health and the different experts that have had on this podcast, Dr. Richard Johnson's work is going to fit perfectly into everything we've covered in the past. I think you're going to enjoy it. Dr. Richard Johnson, thank you for joining the Drew Prood podcast. It's an honor to have you here. As I've mentioned before, while we were chit-chatting before we hit record, I'm a big fan of your work. And I think it's come at such a crucial time, this central message that really, in the context of everything that happened with COVID, obesity being such a big part of it, our entire

global population struggling with the topic of obesity and weight gain, so many people are out there and they're looking for clear guidance and your work is very much in that category. So I'd love to just jump right into things. Before we go into your story and how a kidney doctor end up going down the rabbit hole of this entire work, I want to start off big picture to set up the framework. help our audience understand how it is that actually nature wants us to get fat. And not only is getting fat super important for a whole list of things that you'll get into, it's actually been an incredibly central part of our survival as a species.

Well, thank you for interviewing me. I'm delighted to be here. Yeah, your question about does nature want? us to be fat. Where does that come from? That came from a lot of research that we did that kind of looked at how in nature animals try to get fat for survival purposes. And fat is a good thing if you're in the wild to protect yourself during times of food shortage. So it turns out that animals have developed methods for gaining fat. And by studying how they trigger fat, you know, fat gain, we learned that this was actually a very central mechanism for what drives fat in humans.

And so it's a big story about how you can learn from nature what drives fat. And in the process, apply it to humans and see that we've actually triggered some of the same switches to accumulate fat. So in nature, fat is a survival tool. It helps you during a time when there's no food, like a hibernating animal. or an animal that has to migrate a long distance where there's not food on the way, and they will fly long distances and just survive off the fat that they've stored. So take us to the lens of a little bit of evolutionary history and talk to us about how, at least based on your findings and work and asking around and talking to other top scientists, there was an understanding that this wasn't always the case.

At some point in time in our evolutionary history, we developed this switch, right? This fat switch that allowed us to do this thing. Nowadays, many people are suffering from being overweight or obese and that has all sorts of downstream effects, which we'll get into a little bit later on. But at one point in time, we didn't have that ability. So take us through that landscape and that view of evolutionary history. Okay. So again, you know, when it turns out that the way we, we, we,

were interested in this whole topic was to try to understand obesity from a different angle. So classically, people think the thought was that the reason you get fat is because you're simply eating too much food. There's too many, you know, the servings are too large. There's so much food available and so that we tend to eat too much and we exercise too little. and the result is that we gain weight. But we've known for a long time that this idea or this theory of how obesity occurs is more complicated than that. Because if it was so simple as just eating too much and exercising too little,

we should be able to fix the problem pretty easily. And so we became interested in, you know, how do animals trigger becoming fat? And so, you know, normally animals will regulate their weight perfectly well. So if you take like an animal in the wild and you feed it or you force feed it so that it gains weight. And then, you know, even like by putting a tube down its throat, then, you know, after it gets fat, if you stop overfeeding it, it will actually go right back to its regular weight. And the same thing, if you starve an animal or if you fast an animal so that it loses weight, when you stop that, it will gain weight right back to where it should be.

So animals sort of know what their weight should be, and they regulate it very, very carefully. However, there are certain animals that will recognize that there's going to be danger ahead, like the cold winter that's coming. And animals will prepare for that by gaining weight dramatically. They suddenly like activate a process where they become super hungry and eat a lot more, drink a lot more, put on fat. And this process allows them to get enough fat stores that they can survive a period of food shortage. And this action is, it appears to be like a switch.

because they'll stay in their normal weight for most of the summer. And then in the fall, suddenly they'll start increasing their weight. And they can double their, some of the animals will actually double their weight. And they can increase their fat stores dramatically. Now, what's really interesting is that they don't just increase their fat stores. They also become insulin resistant. And they develop other features that we know of is the metabolizer. syndrome. They'll put fat in their liver, for example, or they'll put fat in their blood, and they'll

develop all these features that we would call the metabolic syndrome. But it's really a type of fat storage. It's really a fat storage syndrome because they're storing fat in their liver and in their blood and in their tissues to help them survive. So when we originally were studying this, You know, we were asking ourselves, you know, what triggers this switch? How is it that animals gain fat? And, you know, what is the evolutionary basis of it? How does it relate to humans? And so forth.

So that's how it all started. And we realized early on that insulin resistance also is a survival mechanism. Insulin resistance is actually a survival mechanism. Because what happens is, you know, in a period where there's not enough food around, it's really important to have enough glucose, which is the main carbohydrate in the blood that provides energy. It's really critical that you have enough glucose in your blood

so that it can provide fuel for the brain because the brain tends to prefer glucose over other fuels. And so when you become insulin resistant, what that means is that the muscle, the liver, and the fat tissues become resistant to insulin's effect to take up glucose. And so because they become resistant, less glucose goes into the muscle, less glucose goes into the fat, less glucose goes into the liver. And as a result, there's more glucose around to go to the brain. And that's critical because if you're going to survive, the organ you have to make sure gets enough energy is the brain. Because if the

brain's not thinking, you're in trouble. So this whole concept of this mechanism of storing fat and becoming insulin resistance and raising blood pressure. Raising blood pressure is great because it helps support the circulation in an animal that could be starving. And so all this, this is like a survival pathway that animals have learned to activate. to help them survive under duress. So the metabolic syndrome is actually in nature is a good thing. It helps the animals survive times of stress and times when there's not much food around. And so the question then was if these animals trigger it, you know, how has it happened?

What dries it? What turns it on and what turns it off? and that's really the summary of what, you know, my research is focused on. And that has also included going into evolution and trying to figure out how humans and our ancestors utilize this switch. So, you know, before I go into the evolutionary basis of it, we probably should begin by just talking about this switch and how it's activated. how it works because once we understand that, then we can delve into the evolution and the history

and then why it is that we've gotten so overweight. Absolutely. I think that's a great place to dive into your story a little bit. How did a kidney doctor start asking what is related to the switch that is impacting all aspects of human health? How did you go down? You did you go down? You Uric acid rabbit hole. It was circuitous for sure, Drew. You know, so I started off, you know, wanting to do some research. And so I began by studying kidney disease because I was studying that as my specialty. And so one of the things about kidney disease is that the kidneys have a very important role in blood pressure.

And because the kidneys, when you eat salt, the kidneys have to handle the salt and they excrete the salt. And it was thought that the cause of high blood pressure, you know, when I was studying this, there was a big thought that high blood pressure was really a kidney problem where the kidney couldn't get rid of its salt. And so as I started studying that, I decided I wanted to figure out what was the problem with the kidney. in patients with high blood pressure. And in the process, we started realizing that subtle damage to the kidney could actually play a role in causing high blood pressure. And that took me to what could cause the subtle damage.

And then I identified uric acid, a substance that circulates in our blood. And many people know it as the cause of gout. And I found that there was some evidence that uric acid could be involved in high blood pressure. And as I studied that, then I began, you know, I kept going down the rabbit hole. And if I could interrupt for just one second, if I could interrupt for just one second, tell us, you know, people know of uric acid in the context of gout, but what is the central function? Because we're going to be talking a lot about uric acid and you're going to go deeper into it and all of its connections inside the body.

But what is the role of uric acid in the body? What was it designed to do and why do we have it in the first place? Well, most people thought of it as a waste. product. So they didn't think of it as having any function at all. So, you know, our bodies consists of protein and fat and carbohydrates, but there's also what's in the nuclei, what we call nucleic acids like DNA and RNA. And there's energy itself is called ATP, the energy that drives our body. And these are all substances that have nucleic acids and components of nucleic acids in them. And one of those components are these little nitrogen-containing compounds called purines.

And these compounds, when DNA or RNA gets degraded, these compounds get broken down, and you end up with a substance called uric acid. So it's sort of a breakdown product from nuclei and from RNA and DNA. And then that substance gets excreted. And most animals, it's actually degraded. There's an enzyme that degrades it to help get rid of it. But we lost that enzyme many millions of years ago. And so we have to excrete it through our kidneys and through our gut. So we get rid of it.

So for years and years, it was thought that this was just a waste product. And if it builds up, like if you eat too much purine-rich foods or foods that can, raise uric acid, or if you have a problem excreting the uric acid, like a kidney problem or something, and that uric acid starts going up in the blood, the problem with it is it can crystallize pretty easily. And so when it crystallizes, it forms these little crystals that are deposit in the joints. And when that happens, it is really painful. And it's a disease called gout. And so it's been known for a long time that things like alcohol and purines and sugar can cause gout because these foods can produce uric acid when they're when they're metabolized so you can

make uric acid from foods but you can also make it when you break down DNA and RNA and so forth so that when this uric acid crystallizes in joints it causes this painful disease there's about, you know, maybe six million people or so in the U.S. that have gout. And it's a type of joint pain. It usually affects the big toe, but it can affect the wrist or knee. It's more common than men. And it's very painful. And then you take an anti-inflammatory and it kind of goes away, the pain goes away.

And you think you're fine, but you still have the high uric acid in your blood. And one of our discoveries was that this high uric acid isn't just a waste product. It does something a lot more. And that it's actually probably an unrecognized cardiovascular risk factor. And it's an unrecognized risk factor for obesity. And it's probably something that everybody should be measuring to have a better. understanding of what their risks are for developing obesity and diabetes and kidney disease. And so our work over the last couple decades has been to better understand uric acid

and to better understand the switch and how it happens. And it turns out that when we were studying uric acid and the kidney and blood pressure, we realized that it was more important than just kidney disease and blood pressure. And so we wanted to know what made the uric acid high in the blood of people. And we started studying the foods that could raise uric acid. And when we started giving sugar to animals, we found that it raised uric acid. And it could raise blood pressure and it could cause kidney disease as we had expected. But when we lowered the uric acid, we had a big surprise.

And the big surprise was that not only did we help prevent the rise in blood pressure and the kidney disease associated with chronic sugar intake, but we also could block some of the effects of metabolic syndrome, such as insulin resistance and obesity and fatty liver and things like this. So we realized suddenly that uric acid was a lot more important than just the cause of gout, that it was involved in a lot of these other disease processes. And that took us down the road that led us to the discovery of this survival switch that animals use and how it works and so forth. So it's a big story. It's a huge story.

I mean, it's led to a whole bunch of expansion. on that original science. And it's really the central, the way I think of it is like, this thing that we thought was not that important turned out to be a canary in the coal mine and an indicator that something else, if it was rising up higher, that something else may be going on in the background. And let's talk about those animal models before we get into human health a little bit. So when you were doing these animal studies and you saw that if you could increase the uric acid, then through, you know, you were feeding the animals sugar, I'd like to know a little bit more

about that. And then if you decrease the uric acid, their health improved a little bit, how are you doing that? What type of sugar were you feeding the animals? And then also, how are you lowering that for the animals that you were studying? Yeah. So I'll tell you that sort of the story as it went. So in the very beginning, we were, as I mentioned, we were trying to figure out what caused high blood pressure. And, you know, there's a lot of people with high blood pressure. And, you know, there's a lot of people with high blood pressure. And we had some evidence that it might be due to some damage to the kidneys. And so we hypothesized that uric acid might be the cause because there were studies showing that people with high uric acid have some subtle damage to their kidneys. And we were

thinking that the uric acid might like form little crystals in the kidney in addition to in the joints and that that would cause low-grade inflammation that could cause hypertension. Well, you know, at that time, no one believed uric acid was doing anything really other than gout. And so it was hard for me to actually persuade the people in my laboratory to do the experiment because no one wanted to spend the time for, quote, a negative experiment. And in fact, in fact, one of the individuals who raised uric acid, you know, We had a way that we would inhibit this enzyme that could break down uric acid. So if we give this enzyme to a laboratory rat, the uric acid would go up a little bit.

And we had done a pilot study of that. We'd seen a little bit of inflammation in the kidney, but it turned out we hadn't measured blood pressure. And so I asked them if they would consider repeating the experiment and measuring the blood pressure. And a gal named Marilda Mazzali, who was a Brazilian nephrologist who was in my lab, said, you know, I'll do it. But I really don't think we're going to see anything. And I said, thank you, Marilla. Thank you so much for doing it. And she did the experiment.

She comes to me like shaking, you know, about six weeks later, four weeks after the four to six weeks later. This is, Rick, you won't believe it. But the animals developed high blood pressure. I go, what? You know, if uric acid caused high blood pressure, you'd think the world would know it. It's been around a long time. She said, no, they've really got high blood pressure. So I was initially really nervous about doing it, about publishing this, because no one would believe it. So I had her, made her do like 100 plus animals. And we did all these different ways where we would stop the uricase inhibitor or the inhibitor that caused the uric acid to go up. where we treated them and we treated them different ways.

And if we lowered the uric acid, we lowered the blood pressure and it was no good. The data was just too strong. And it was true. And so that was the beginning. And then we go, oh, my gosh, you know, if uric acid's raising blood pressure, what's raising the uric acid? And it turned out that, you know, like red meats can raise uric acid and purring rich foods, shrimp and things like that.

But what wasn't really totally an alcohol can. But what wasn't totally appreciated back then was that sugar, sugar itself also can raise uric acid. And normally we don't think of carbohydrates as raising uric acid, but sugar contains fructose. And so sugar or table sugar is sucrose. It's a disaccharide. And it's a molecule of glucose and a molecule of fructose. and they're bound together. So it's really two sugars in one.

And when you eat sugar, you break up the glucose and the fructose, and then each of those get metabolized. And glucose and fructose, they look very, very similar. They're six carbon sugars, but they're very different. And it turns out that fructose generates uric acid and glucose does not. And so when you eat fructose, your uric acid is formed within minutes, and it even goes up in the blood. And so if you drink a soft drink that has a high fructose corn syrup,

and that's like got fructose and glucose mixed together, or if it has table sugar, which is sucrose, that has fructose in it. When you eat that, the uric acid will go up in the blood, and it goes up in the cell. And so uric acid is generated from sugar. So then we said, okay, well, let's do this experiment where we give fructose or sugar to rats. And a young guy named Taka Nakagawa, a Japanese scientist, decided to do the experiment.

And so we fed these animals fructose. And sure enough, their uric acid went up, their blood pressure went up. All the things that we thought would happen, happened, and we lowered the uric acid with a drug, and the blood pressure came down. It was like incredible. and along with the uric acid. But the incredible thing was that they also showed an improvement in other features from sugar, like they were less fat.

They didn't have the triglystriids in their blood was dampened. Their fatty liver was less. Their weight was less. And we go, oh, my God, lowering uric acid is affecting not just blood pressure. it is affecting the whole effects of sugar to cause obesity and metabolic syndrome. And how can this be? Because the animals are still eating the same amount of sugar. It can't be calories.

It can't be the calories. And this was like a big discovery. This was around 2005 or so. And we said, how can this be? Everybody thinks that obesity is because you're eating too much. and here we are, you know, blocking a pathway where uric acid is being generated, and it's not even in the caloric pathway. It's not from the calories. It's like a side chain reaction.

And how could that be? And that's what made us start studying fructose and glucose and why fructose was so distinct in its ability to cause. obesity. And then pretty quickly we learned, and I can talk about this, how fructose is actually the driver of insulin resistance and obesity. And glucose is really not. And so we can talk about that because I think there's some controversy on that in the literature. Yeah. And I want to dive into that for a second. But I just want the audience to really get the magnitude of this. You know, if you live in, you know, North America, but really if you're anywhere in the world, you know, that we've had, as the standard American diet has been exported all around the world,

we've had a quasi war on fat, quasi-war on obesity that's been going on for quite some time now, probably at least to like the, you know, somewhere between the 1940s and 50s, when it really started to be something that we all paid attention to because all of a sudden now society is going through a whole host of problems, including seeing an explosion of obesity. And since that time, in one way or another, the general answer from government, research institutions, organizations has been, hey, this is an energy balance issue. We're taking in too much calories or we're not spending enough energy through exercise. So if we just took in less calories and if we worked out more, then this whole situation would go away. And

anybody who's been looking around has seen that that advice has been shared so ubiquitously, but it just hasn't worked. In fact, if anything, we've gone even further down the rabbit hole of more obesity and more metabolic syndrome that's impacted people. And now, through partly your studies that you guys are doing,

there's this recognition of, whoa, whoa, maybe the calories in and calories out, idea is completely, or at least partly, like, as a main driver, is missing the boat when it comes to what actually is making us fat. This is a whole upending of a way of thinking about what the driver of obesity and metabolic syndrome is in our modern life. So, I mean, that is kind of freaking amazing. Yeah. So thank you. Thank you for those kind words. So when we, when we saw the,

that the uric acid could have an effect. And it wasn't, quote, through the calorie mechanism. We wanted to actually better understand the role of calories in obesity because of this very controversy that you're talking about. And, you know, there were people saying, well, especially from the high fructose corn syrup industry, the people are saying, hey, sugar isn't the cause of obesity. It's the fact that you want second helpings. It's the fact that you're going back for more.

Sugar, you know, is just an empty calorie. It may not be nutritionally good, but it's not causing obesity. It's too many calories, that is. And so we wanted to look at that more carefully. And so the way we did that was to try to distinguish caloric, or to separate the effects of caloric intake from the effects of sugar. And the first way we did this, and actually Taka did this in his original papers, what we did was we took laboratory animals and we fed them sugar like 40% sugar diet or like a 30%. But, you know, I think there was 40% sugar versus 40% carbohydrate that was not sugar.

and actually it was like a 60% carbohydrate diet, 40% sugar, 20% carbohydrate, other cause, versus 60% carbohydrate and the same amount of protein and fat. And then what we did is we fed all the animals the same amount of food. They were not allowed to go back for seconds. So it was very controlled. Every animal ate the same amount of food. And what we found was that when you controlled for food intake, weight gain was almost the same between the two groups. It tended to be a little higher in the sugar group.

But weight gain itself did not show that much difference, but everything else showed great differences. So the sugar-fed animals were diabetic and insulin resistant and had fatty liver and had high fats in their blood and had high blood pressure. and the control rats that ate starch, they did not show that. And so the main difference was in weight, the main difference was in metabolic syndrome, but the differences in weight were relatively minor. And when we delved into that, here's what we found. What we found was that sugar and especially fructose caused animals to become hungry. And we actually identified the mechanism.

and they became resistant to a hormone that makes people feel full. So this hormone called leptin comes from the fat, and it tells us when we feel full, this is what we call satiety response. And when we gave fructose, they lost that satiety response. They lost that sense of feeling full, and they became resistant to the effects of leptin. So normally if you inject leptin in an animal,

they'll quit eating or they'll reduce their intake. But if you inject a fructose-fed animal with leptin, they continue to eat. They continue to eat. And so what happens was when you give them fructose, the animals get hungry. They want to eat more. So if it's an ad-lebitum diet where they can eat all they want, the fructose-fed animals will eat more and they will gain fat. And also, if you give them high fat diet and with sugar or fructose, they can really gain weight

because the high fat diet is energy dense. It's like nine calories a gram, whereas carbohydrates and protein are four calories a gram. So they eat one gram of food. They get twice the amount of energy. So if you give an animal that is leptin resistant from fructose, and you give it a high fat diet, it gains a lot of weight because weight gain is driven by food, largely by food intake and a little bit less by the drop in energy metabolism. So when you give fructose, energy metabolism falls so that for the same amount of food, they do gain a little weight, but it's relatively small relative to their hunger.

So they eat a lot more. So if you, on an ad libidum diet where you can eat all you want, a fructose-fed animal will gain weight. And especially if you give it a high-fat diet with it, it will eat all that and gain a lot of weight. But if you control it so it can't gain weight by giving all the animals the same amount of calories, it gains a little weight because the energy metabolism is slower. So it doesn't metabolize food as fast.

So there is a little weight gain, but it's not huge. but all the other effects like fatty liver, diabetes, insulin resistance, they occur independent of the food intake, you know? So actually, Carlos Roncal, who's in my lab, did an experiment where he did the parapheding with sugar versus starch. And what he did was, you know, parapheating is where you, you know, what you do is you start off by feeding all the animals the same amount of food. But there's usually one animal that doesn't eat as much. And so then you measure how much that animal eats. And the next day,

every animal eats the same as the animal that ate the least the day before. And what that does is all the animals end up eating the same amount of food. And that way, because it's the guy that eats the least, that's what everybody gets. And they don't get any more. Well, unfortunately, that one little animal turned out to have cancer. And that's why he didn't want to eat. And so everybody was basically on a starvation diet. They were eating like about 80% of what they normally eat. But after three months, or maybe it was four months, but it was three or four months later, we sacrificed the laboratory animals, and the animals that were on the sugar diet had all become diabetic. They were all had fatty liver, even on a severe diet restriction.

And around that time, I saw a patient who was eating very little, but was eating primarily sugar. And she actually developed the same syndrome. She developed fatty liver, hypertension, actually develops significant enough liver disease that she had to get admitted to the hospital. And she was actually a bodybuilder. And she was just, you know, kind of eating sparingly. And it was eating the wrong food. And so she was actually doing the same thing inadvertently. And thankfully, we were able to intervene and help her.

But yeah, sugar and fridose. So a couple of takeaways that I'm hearing from that, that I think that are really key is that even if the diet is controlled and everyone's eating the same calories in the case of the laboratory animals and then we'll extrapolate it to human beings, you might see a moderate increase in weight gain from the animals that had the sugar, but really all the other markers of health that you had mentioned, those were headed in the wrong direction even though the animal wasn't gaining weight. So same thing, you could have a human being that's eating a diet that's high in fructose,

whether that's high fructose corn syrup, but also even fruit juices, which we're going to get into in a second. You know, there's a lot of people that are listening to this podcast. They're like, well, I don't really have a lot of high fructose corn syrup in my diet. Well, do you drink fruit juice? And that could be a little bit problematic, not fruits necessarily, but fruit juice. We'll talk about them in a second. So having, even if you're not gaining weight, you could still develop a whole host of issues like

non-alcoholic fatty liver disease. you know, I had a friend of mine who just texted me the other day, and he's, you know, in his mid, early 40s, healthy young guy who, you know, healthy from what somebody would say from the outside, they'd look at him and say, he looks pretty good. He's not overweight, right? He's got a little bit of muscle. He works out, other things. And he texted me and he said, dude, we got to talk.

I just got diagnosed with non-alcoholic fatty liver disease. Like, I want any kind of resources or doctors that you think I should talk to, like, how the heck is this happening? And he's a vegetarian. You know, he's for religious reasons, other things like that. So in his eyes, he's thinking that he's eating a healthy diet and how is he ended up with non-alcoholic fatty liver disease, which we'll chat about in a second. So just incredibly profound to see that even if you're eating a diet that's high in sugar, and there's plenty of people that are out there that are, especially with fructose, they're like, look at me, I'm fine.

I'm not overweight. I'm not obese. But that doesn't actually mean that you're healthy on the inside when we look at some of the key markers that are there. Absolutely right, Drew. That's absolutely right. In fact, we published on fatty liver and lean subjects. And we've found that they often have a high uric acid. And so, and we know that the uric acid is involved in the mechanism.

by which fatty liver is developing. And usually there is some source of fructose. But it doesn't absolutely have to be fructose because you can generate the uric acid other ways as well. But you're right. Fruit juices is one of the secret causes of fatty liver that's not appreciated. And it's because fruit juice also has fructose.

So it's a little bit confusing for people because, you know, when we were studying this, we realized that fructose could cause metabolic syndrome. And so when we started looking at animals, we found that many animals that develop obesity were eating lots of fruit. So like bears and other animals, birds before they migrate in the fall, they often are eating a lot of fruit. And the fruit contains fructose. and we could show, you know, I mean, in some of these animals, that we, you know, we can absolutely demonstrate that the fruit dose likely has a big role in driving the metabolic syndrome, especially from our laboratory studies.

And so the question is, you know, we, everyone's taught that fruit's healthy, and yet how is it that animals are using fruit to get obese? You know, when we're told that we should be having three or four or five servings of natural fruit a day. And so this was a paradox that we had to kind of address. And what we've learned is that the first thing is that when animals eat fruit to gain weight, they're eating a large numbers of fruit. Like the orangutane will go to a tree and eat like a hundred fruit or more at one sitting. And the bear will eat like 10,000 grapes in one 24-hour period. They can tell by measuring it in the scat. And so they're eating a large amount of ripe fruit. And it's

interesting that as fruit ripens, the sugar content goes up. And a lot of the good things like vitamin C go down. And so the fruit tends to, the fruit that animals prefer tends to be ripe, rich in sugar, they eat a lot of it. We, we eat like one or two fruit at a time often. It's usually more tart. It's higher in vitamin C and fiber and all kinds of things that are good. So vitamin C actually can neutralize part of the effects of fructose. And so can other things in the fruit like potassium and things like flavonols, which are substances and fruit. And fiber helps slow the fruit dose from being absorbed. So when we eat natural fruits, also a natural fruit has only like four to eight grams of fruit dose normally. I mean, there's some exceptions. But most fruits...

When you're eating it in its whole form. You're talking about that one in a totally. Whereas, you know, if you drink a soft drink, you can get 20 grams or 30 grams of fructose and one swig, you know, one drink. And so there's a huge difference in the amount. And so when we eat natural fruits, we're not getting that huge dose of fruit dose. Now, the exception is when you make fruit juice, because when you drink fruit juice, oftentimes they'll remove the fiber. It's multiple fruit that you get the juice from. And so it's a higher amount of sugar and you tend to drink it so you drink it fast. And a lot of the good things are removed when you juice it because a lot of the good stuff is in the fiber. And so fruit juice has been associated with obesity in children, especially.

And so the pediatricians have actually recommended limiting the amount of fruit juice to children. And we should limit it to us, too, because it's a large amount of sugar that you can drink very rapidly and then that can get you into trouble. Whereas natural fruit has all the good things. So I actually, we actually did a study where we took people and we put them on a low sugar diet, a low high fructose corn syrup, low sugar diet where we reduced the fructose in their diet down to, and one group was also on a low fruit diet. And the other group got to eat natural fruits, but they just couldn't eat refined sugars. And we found that both had great benefit.

they had equal benefit on most things in some areas the low fruit i mean excuse me the low sugar modest amount of fruit was actually better as a diet than the other one it was probably liked more and it was associated with equivalent or better effects on the metabolic syndrome in this overweight population that we did so really what i'm hearing from you on the takeaway that is that fruit can be and should be a healthy part of what would be our modern, well-balanced diet, right? As long as we're not drinking our calories, really, that's one of the biggest takeaways that have gotten from your work, whether that comes in the form of sodas or other things, but also in the form of natural sugars that contain high amounts of fructose, like fruit juices

or fruit smoothies. It's amazing that even many people that are, my friend, friends, again, well-intentioned, are making these incredible smoothies each morning, whether they put a lot of great stuff in, and they might throw in enough fruit or coconut water or fruit juices that if you look at the sugar content and the fructose content of this smoothie that they're having, it rivals many sodas that are out there. And when they wear a continuous glucose monitor, they see as big a spike, if not a bigger spike, on that smoothie that's loaded with fructose than they would on drinking like a bottle. of Coca-Cola. Absolutely. So, yeah, fruit juice, I mean, like apple juice is probably the same

sugar content as a soft drink. And so there's a huge amount of fruit dose in fruit juice. And also dried fruit, you know, dry fruit also is a lot of it is sugar. We love dry fruit. I mean, who doesn't like, you know, dried fruit? It tastes so good. But the trouble is it's, it's a lot of it is fruit dose and a lot of the good things have been removed. So I don't recommend that either. And likewise, if you're going to eat natural fruit, natural fruit's wonderful. I recommend it, especially like if you're hungry or if you have a craving for something sweet, a natural fruit is perfect.

But if you like get a bowl of whole bowl of grapes and you eat them watching TV, that's not going to be good because if you eat a large amount of, amount of, a very large amount of fruit, it's going to catch up with you. And I've had patients who've had trouble losing weight and it turns out that they're doing fruit smoothies or, or they have these bowls of large amounts of fruit. Now, you know, there are different kinds of fruits. So some fruits are healthier than others. And the berries, for example, strawberries, blueberries have very little fruit in a lot of, I mean, a fructose relative to all these other good. things that they carry. And so like a bowl of berries is is probably very healthy, whereas a bowl of

grapes, which are more sugary and have a higher fructose content, it would probably not be good. But I do go through that in my book. I have tables showing which fruits are safer than others and so forth. Yeah, and we have a link to the book and the show notes. And we're also going to have you back for a round two where we're going to go deeper into a lot of audience questions and other things. But for right now, we're going to go through some of the questions that I've put together. And there's one question that I have on this topic of fruit. As I became more aware of the world of metabolic health, my business partner, you'll be on his podcast soon. Dr. Mark Hyman, he wrote one of the flagship books in this category. And I started to realize that, okay, great, it's

about personalizing your diet appropriately to you. And I started to measure out how much is too much sugar. How much is not enough sugar? How do you get the benefits of a lot of the flavanoids and phytochemicals that come along with fruit? But how do you make sure that you're not having so much that it's out of control and it, you know, it elevates your average level of blood glucose and then through reading your work has downstream effects and raises your uric acid? So I want to ask you about the examples that you shared earlier. I was on a hike one time up at Glacier National Park in right on the border of, you know, the U.S. and Canada up in Montana. And the guide that I had that was working with us, she was like, you know what, I'm going to take you on this really cool hike.

We're going to take a little edible hike. I'm going to take you down and I'm going to show you all these different berries and other things that we can eat. And I'm really big into that. Anytime I can get wild foods, I'm really all about that. So she took me around this corner and she was like, you know what? And it was right before the winter season. They were just about to close the park. All the snow was about to come.

So I made it in right before then. And she took us around this corner and this bend. And all the berry trees had been completely decimated. I know where you're going. And I was like, oh, there's no more berries left. What happened? She's like, it's actually the bears. We have to be very careful because this time of year,

the bears will come. And this was probably one bear that had eaten, like, multiple trees and bushes and it was a large amount of berries that they would have had at the time. And that's what it really hit home for me, even though I knew a lot of this information, that, wow, these animals are stocking up on all this fruit, fructose, to put on belly fat because they're about to go into hibernation right before the winter season comes up. Now, I want to ask you, based on your research in the work that's out there, and you gave the example of the orangutan going and eating a ton of fruit at one time or the bear eating that,

Do a lot of animals have access to, and do they eat a lot of fruit throughout the year? Are they only doing it right before hibernation when it's summertime and it's a warmer climate? Are they eating the same amount of fruit? What have you seen out there? Yeah, so it depends on the animal. So like the bear will typically eat the fruit in the fall. And in fact, there's studies that show that the first frost leads to the fruit sweetening a little bit. And they'll often go out right after that. I do have to tell you,

I went to Glacier National Park myself 30 years ago, and I was hiking probably not far from you, and I ran into a grizzly bear. Oh my God. And I had to get out of there as fast as possible. But anyway. I'm glad you made it. So my. But anyway, but like, for example, there's a fish called the Paku fish. It lives in the Amazon. And it waits. So in the Amazon, there's yearly floods. And when the Amazon floods, the river basically spreads out into the jungle. And it becomes like this huge, almost like a lake that goes out and out for kilometers.

And so what happens is the fruit trees get or become part of the, you know, it's inundated from the river. And the fish will swim under these fruit trees. trees and they wait and the timing of the floods are associated with the timing when the fruit ripens and falls into the water and these fish will actually they kind of look like toothless piranus and they will they love fruit and they will eat the fruit and they'll eat huge amounts and then they increase their fat especially in their liver and elsewhere and then they will not eat for like six months as the amazon regresses back to the river. It's the river. it doesn't really like the food, the other kinds of food and it will just live off its fat.

And likewise, those orangutans, when they find those fruit season and they eat all those fruit, they actually, there's studies that show that they gain weight, they become fat, they've activated this switch. We can talk about how the switch works soon. And they basically gain this fat. And then they, again, through much of the rest of the year, they don't get a lot of calories from the leaves and stuff that they eat. And they actually are burning their fat during that time. There's a lemur in Madagascar that also does the same thing.

It eats a lot of fruit, gains fat, and it actually puts the fat in its tail. So it's called the fat-tailed lemur. And that lemur then will hibernate, but it's in this, it's in the, the warm weather. So it's got a different name. It's called estivation, but it's really the same thing as hibernation. And during that time, it'll be living off the fat. One of the things that's really interesting about this is that the fat provides not just calories, but the fat, when it's broken down, actually produces water. So it turns out that when they make this fat, the lemur, it's actually breaking down the fat to provide water through the dry season.

So it tends to, it will actually use the fat not just for calories, but for water. Because while it's estivating or hibernating, it needs both water and calories. And the same thing's true for the bear. While it's hibernating and it's breaking down that fat, it's actually using the water that's coming from the fat breakdown to also give it water. So it turns out that fat is a survival mechanism, but it's not just providing calories. It's also providing water. And these animals use it. But you raised a very interesting question because, and it was the one that we were thinking about, which is, you know, not all animals are eating fruit. And so how do other animals gain fat?

how does the camel get its fat? And how do, you know, other animals like squirrels and so forth that may not eat so much fruit, how do they gain fat? And what about us? Not everyone's eating sugar and yet we're getting fat. And so this was kind of one of our big breakthroughs, Drew, was that we discovered that people get fructose not just from the sugar we eat, but that our bodies can make fructose. This was a big breakthrough. And we've identified a number of ways that our body makes fructose. And we can actually show that when that happens,

that the fruit dose actually can drive obesity. And it turns out that this is the way high glycemic carbs actually cause obesity. And I don't know if you want me to go into that story. Please, no, go into it. I think our audience is like listening, like sitting on their head like, whoa, okay, let's go into it. Okay, well, you know, so when this, when we discovered that fructose could really cause the metabolic syndrome and it was like really major leak. I thought that maybe we could cure obesity just by cutting out fructose.

And I was wondering if, you know, the low-carb diet was beneficial, mainly because it reduced fructose, not because it reduced potatoes and rice and so forth that are filled with starch, but not sugar. And so I was thinking that obesity was really from sugar and from fructose. And I was on, I got interviewed by Jimmy Moore, and he told me how he had to actually restrict all carbs to really lose weight. And actually it became apparent to me that things like bread and rice and potatoes were fattening. And, you know, the insulin hypothesis was very strong.

And that hypothesis is that, well, fat really is driven by insulin. and when you become, when you eat carbs like potatoes and rice and your glucose levels go up, that that stimulates insulin, and then the insulin puts the fat into the fat tissues, or generates fat in the fat tissues, and dries obesity. And it seemed true, you know, if you could control your blood glucose and get a glucose monitor and keep your glucose levels low. And if you go on a low-carb diet, you could really lose weight. And so people were talking about things like glycemic index. And they say, well, you should eat foods that have a low glycemic index because that will keep the glucose levels in your blood low.

And that will prevent you from getting obesity. And yet fructose, when you eat it, it actually doesn't make blood glucose go up. Fruit dose levels go up in your blood. Glucose levels do not, at least initially. And so fructose has a low glycemic index, and yet here I was finding it was like the cause of metabolic syndrome. So it was like another paradox. It was another paradox. And so what we decided to do was to, you know, when we gave animals fructose, especially in their drinking water, they got really, really fat. So we thought to ourselves, well, let's do the same thing with glucose. Let's just give them glucose in their drinking water.

And this way they're going to stimulate insulin and let's see if they get fat. And they did get fat. They over the same time, they actually got fat. They got full metabolic syndrome. And so it kind of looked like glucose was also causing metabolic syndrome, probably through, but it wasn't raising uric acid, it seemed, right? It didn't seem like the uric acid in the blood wasn't going up. And so the question was, well, you know, how is this happening when you've been,

could it be the two mechanisms? But then we realized that, you know, the body can make fructose. And there's only one way the body makes fructose. It's an enzyme reaction. And it's driven by chemical reactions that can occur like in the liver and stuff. And one of the stimulus for making fructose is a high glucose. And when the blood glucose goes up, fructose synthesis can be turned on. And also when you eat rice or potatoes or things like that,

the glucose is released from the starch in the potato. and then that glucose gets to the liver. So the glucose and the liver goes high, and that we know can trigger the reaction to make fructose. And so what we did was we gave glucose to laboratory mice, and we measured fructose production, and we found that they were making large amounts of fructose in their liver, maybe one quarter of the glucose they were eating,

was being converted to fructose on a very high glucose diet. And the fructose was activating this switch in the liver. And we could show the evidence that the switch was being activated. And uric acid was being generated, but it was being generated mainly in the liver. There was a little bit going up in the blood, but most of it was in the liver. And it was driving this process.

So the way we proved that is we gave glucose to animals that could not break down fructose. These were special genetically modified animals where we blocked their ability to metabolize fructose. And when we did that, they ate all the glucose they wanted. And when they ate the glucose, insulin levels would go up in their blood, but only while they're eating the glucose. And so the insulin levels went up. And the animals gained a little bit of fat, but not a lot. And they didn't get insulin resistant. And they didn't get fatty liver.

And they didn't get hypertensive. You know, I mean, it was really a protective, I mean, the animals that couldn't metabolize fructose were pretty safe from the glucose. And so, but what we think, you know, I know that Dr. Bickman was recently talking to you. And I think that we can combine and explain both stories this way. Because what happens is when you, if you give glucose to an animal, what happens is they generate fructose in their body and then they become insulin resistant. Remember, that's part of the metabolic syndrome that fructose drives.

So insulin levels go up. And the insulin blocks, they have insulin resistant. so the insulin can't move glucose into the liver or fat or muscle, but it turns out that it's a selective insulin resistance so that the fat cell still responds to the insulin in terms of breaking down fat. Insulin blocks the ability of fat to break down. And so what happens is when the insulin levels go up, it makes the fat tissue unable to burn the.

the fat. And so the fat accumulates over time. So the fat still goes up. It's still driven by insulin because insulin is blocking the fat breakdown. But it's actually farther back, the fructose is playing a role. So it's actually not so much that glucose is stimulating insulin, but that glucose is stimulating fructose. The fructose is causing insulin resistance. And the high insulin levels are affecting the ability to burn fat. And so the story is the same. It's just the explanation is slightly modified. And we also went ahead and to really prove that this was the mechanism, we fed animals soft drinks. And we made a soft drink with high fructose corn syrup. And we put it in their drinking water. So the animals were drinking basically soft drinks around the clock.

and they get really, really fat. They get metabolic syndrome. They get all the things we talked about. And the high fructose corn syrup has both glucose and fructose in it, right? It's a mixture. So they're getting glucose and they're getting fructose. But in these animals, we blocked the ability of them. We gave it to animals that could not break down fructose.

They have normal metabolism of glucose. Insulin still goes up, all that. But when we did that, we completely blocked obesity. metabolic syndrome, everything in these animals. So most of the metabolic syndrome from carbs is because the carbs are raising blood sugar. But it's not, the blood sugar is then triggering fructose and that fructose is then driving the process. So I believe in continuous glucose monitors. I think they're wonderful. I actually have one. I'm proud of it. I use it. to monitor what foods I respond, you know, cause my glucose levels to go up.

And I try to keep my glucose levels down because I'm aware that when the glucose levels are high, I start making fructose and that's going to counter, that's going to sort of drive me down a path to become fat and insulin resistant, which I don't want. So a lot of people are listening to this and already they're extrapolating some of the messaging from these animal studies to human beings. One of them from earlier being shared, we don't want to be drinking our sugars, right? We don't want to be drinking our sugars,

even if you're not drinking sodas and high-fructose corn syrup, even things like fruit juice can be in large quantities. You're having it every day, you know, a couple glasses of orange juice or apple juice or, you know, we feed kids so much fruit juice that's out there and we think of it as a better alternative to Gatorade and other things like that, but we've talked about why that can be problematic. And then separately from this last chunk that you shared, where it's talking about

when it comes to carbohydrates and glucose levels and their ability to still trigger fructose production, which can trigger uric acid production, which can then trigger a whole bunch of other things that are there, what do you think some of the takeaways are when it comes to people who are trying to figure out, okay, you know, what should my diet be based around. Okay, well, there's a lot of questions there. You know, so one of the very first points that you made was the importance of liquid sugar versus solid sugar. Of course, both are bad, but liquid sugar tends to be worse. And the reason is, is because what drives this survival reaction, this switch, is the concentration of fructose that the liver sees. So if you

drank a huge amount of fruit dose like a soft drink, like if you drank a soft drink, you'll absorb it very rapidly because it goes down very quickly. And so it's like a wave. The fructose hits the liver very, the concentration tends to be very high because you've taken it in a very short time and a lot of it at the same time. And so that really turns on the switch triggers this big reaction to

become fat and, you know, develop metabolic syndrome. On the other hand, if you eat sugar and it's in the middle of a meal and, you know, and there's lots of other food present and there's fiber present and everything, then the amount of sugar that's absorbed will, you can still absorb a lot, but it will have to be, it'll probably be slowed down by the other foods, by the fiber and presence of other foods. And so the concentration that the liver sees of fructose may be less even for the same amount of sugar. And so studies have been done where you give liquid sugar versus solid sugar. And if you take liquid sugar, you get much more of a metabolic effect

than, for example, jelly beans. And we've written about this. because there's a lot of epidemiology to support this as well, that liquid sugar tends to be worse than solid sugar, especially on an empty stomach, because it leads to a faster absorption of fructose and so forth. So if you had a soft drink and you sipped it over a three-hour period, it would probably just be like calories. But if you drank it fast,

that's when it will trigger this reaction in the body that causes this switch. And that switch, just to chat about that for just one second, we have to understand that this is your body. You know, so many people, when they start to gain weight or they notice that their body doesn't look the way that they want to based on their expectations or whatever maybe society expects people to be. We think of it as our body failing us. And in this instance, when we get this flood of fructose into the body all at once, our body is actually doing the job from my understanding of reading your. material, our body is doing the job that it thinks it wants us to do, which is, oh, shoot, winter's coming, let me put on some weight and get ready for what's going to come ahead. Yeah, actually, this is a really big point that you bring up.

And it relates to the discovery of how this switch works. And when you metabolize glucose, actually, whenever you eat any kind of food, you eat the food to generate energy. And the energy then is used to help drive what you're going to do. You're going to walk, you're going to talk, you're going to run, you're going to, whatever, you swim. That's all driven by the energy that we get from the food we eat. And that energy is called ATP. If we have excess energy, we can store that as fat or as we can store it as carbohydrate, too, like glycogen. And then when we need energy, we can break down the fat or break down the glycogen to make more ATP. So you don't have to always have the ATP from the food you eat. You can make the ATP from the fat and so forth

that you store. But all foods are used to make ATP. But the problem is, is that when you eat food, there's a little bit of cost to digesting it. There's a little bit of cost. There's a little bit of cost to breaking it down. And so we end up using some energy to make energy. It's like, okay, we're going to eat this plate of food. We're going to actually spend some energy to convert that food into energy. And so there's always a little bit of cost, energy costs, to breaking down food, digesting it, and metabolizing it. In almost all systems, when we start breaking down the food, and we start making energy from it. There's a system that keeps energy levels high.

The body does not want to drop the energy levels in the body because that's how we drive everything we do is through energy. So if we start using too much energy to break down energy, there's a feedback system, a system that says, hey, stop. And so like when you're eating glucose, even though there's some energy, that's used to metabolize the glucose, there's this very, very careful system that keeps energy levels high at all time. So if you start burning too much energy, it just slows the reaction. It's going to slow that reaction, stop the reaction until you have enough energy, and then you can

metabolize it. So when you eat glucose, you maintain your energy levels high at all time. But when you eat fructose, it's like the only nutrient. It's really the only nutrient that causes the energy to fall in the cell. Alcohol, if you consider that a nutrient, it can do the same. But fructose, when you eat it, the energy that's used to consume it, there's no feedback system. It's like a runaway train. As soon as you start eating the fructose, the energy levels start to fall. If you get a big slug of fructose, if the concentration is really high because you drink a liquid drink, then the drop in energy is more severe. And when that energy drops, it causes the ATP and the phosphate levels to drop in the cell. And when that happens, it triggers a reaction.

The fructose triggers a reaction that keeps the energy levels low for a longer period of time before it recovers. And so what happens is when you eat sugar, even though you may have a lot of stored energy. You have fat, you have all the stuff. Inside the cell, there's this drop in ATP that makes the animal feel like it's starving. It makes the animal feel like it's in danger. And that is what triggers the animal to store fat, to go up, to become hungry, to become thirsty, to start foraging for food and doing all these reactions to go out there to try to gain weight because this drop in energy is like an activation. It's an alarm signal. And that's how it works.

And so most foods don't do that, but fructose does. And so when it does, it triggers this metabolic syndrome, the survival pathway. And it's a brilliant system for nature, right? Because you can be fat. You can have some stores. But as you eat the sugar, you're going to go out and try to store more fat. So you're going to increase your weight above your normal weights. You're going to keep going because it wants.

you're eating that sugar to prepare for the crisis that's coming because nature doesn't want you to suddenly be starving and and you know and have no fat stores and be in trouble so this way it's it creates a pseudo kind of a fake starvation state because you actually do have all these stories but by faking the starvation state it makes you eat makes you accumulate that fat and and it's like great because that way you're going to survive the winner. Yeah, these tools were all part of a time in history where we didn't have the abundance of food and grocery stores and the ability. So we have now all the resources to have food, processed carbohydrates, fructose, glucose,

everything. We can have all that around us at all times. And we have an abundance in most parts of the world, right? We used to have a society where there were more people dying of hunger. than there were people dying of diseases of obesity. Now it's sort of flipped around. There are still people that are out there in the world and we have a challenge of distribution

and it's a major problem, but largely most of the world has access to a sense of abundance of components. Now, this wasn't always that way and you've talked about how some of the research that's out there and some of the fossil records have shown that there was a period in our time, our history of our ape ancestors,

I guess you could say, is if that's the correct term, that they developed this evolutionary switch based on sort of, or this preference based on a group of apes that ended up surviving out of a major crisis. Talk to us a little bit more about that. I might have jumbled that up a little bit, but I want to hear your version of it. Yeah, sure. So, you know, when we found that this switch was occurring from fructose, you know, the immediate thought was that the reason that we have so much obesity today is because of all the sugar we're eating. And so initially my interest focused on, you know, when sugar was introduced, and sure enough, you can show that weight gain and obesity really tracks with sugar intake. But we had this insight that there might be another

mechanism driving obesity besides this change in diet and that it could have an evolutionary basis. And what we were, what I was interested in was this observation that humans tend to have higher uric acid levels than other mammals. And so we have much higher uric acid levels than most mammals. And here we had found that uric acid was playing a very important role in this fat switch. And what we, which I hadn't explained to you yet, but when this energy level drops, uric acid is generated in the cell. And that uric acid then goes and causes changes that activate this metabolic switch. So the uric acid goes to the mitochondria and causes oxidative stress and other.

other things and that triggers all these changes for the Metabox syndrome. So a high uric acid could be a bad thing and high uric acids associated with the higher we have it, the more likely we're obese, the more likely we have heart disease, the more likely we have diabetes. So uric acids in our human population tend to be higher than in other mammals, but within our population, those that have the highest uric acid tend to be the ones that have obesity and type 2 diabetes and so forth. So there seems to be this range. And a normal uric acid in most mammals is around like 1 milligram or 2 milligram per decilator. It's a very low concentration. In our society,

uric acid levels usually run about 5 or 6. And if you're overweight, it tends to be higher, 6, 7, 8. levels. And so the question is, you know, why is it that humans have high uric acid levels? And it turns out that most mammals have an enzyme called uricase. And this enzyme degrades uric acid so that most mammals have low uric acid levels, like one or two, as I mentioned. And but humans have a higher one because we do not have uricase. And the question is, why don't we have uric acid levels? And the question is, why don't we have euricase when all these other mammals do. And it turns out that we had a mutation that wiped it out. Euricase became, was no longer, we no longer have Euricase because we lost it from a mutation. So I became interested in that mutation, you know, like, when did that occur? Why did it occur?

And so I started reading about it and I realized that it was a mutation that occurred 15 million years ago. And I thought, well, that's a long, long time ago. And it turns out that that was during a period called the Miocene. And during that time, there was, you know, our ancestors were apes. They were some of the earliest, the earliest apes had just developed around 24 million years ago. And that was the first, the first apes evolved in East Africa right around that time. And those apes were very, very successful. And they did very well.

And in a period of just two or three million years, it went from one species to maybe more than 10 species of ape. And they lived in trees. They lived in the tropical rainforest. And they ate fruit as their primary food. I mean, that's really what they ate. And so 90% of their food was from fruit. And they were doing very well. And then what happened was right around, you know, like 18, 17 million years ago,

suddenly the world started getting colder. And there was a period of global cooling. And the ice caps formed in the poles. And the sea levels dropped. In Africa, which had been, you know, isolated from Europe and Asia, suddenly there was the formation of a land bridge. and these apes that were living in the East African tropical forests were able to migrate into Europe and Asia. And there they were living like in present-day Turkey and in Europe.

And what happened was they were initially, they could eat fruit all year round because it was still warm there. It had been a period of warming, a warm climate, and it started cooling, though, with this global cooling. And so initially, they could eat fruit all year round, and they were living in, like, woodlands and so forth. And their favorite fruit was the fig, because the fig can actually has a deal with the fig wasp, where the fig wasc can pollinate it off and on any time during the year. So when there's figs, fig trees, they tend to fruit all. all year round depending upon the tree and the fig wasp and so forth. So it was a wonder, and it's very rich in sugar and fructose.

And so these apes were doing very well. And then as global cooling worsened, these apes started to retreat to small colonies. And at that point, there were a little isolated, what we call refugia, or little colonies of apes living in Europe. And then by maybe eight million years ago, they became extinct in Europe because as cooling continued, the forests, the figs died out. There was no fruit. And there's evidence that they were starving, seasonal starvation. So during the winter, there wasn't enough food for them.

And during those cooler seasons, they were actually starving. And there was an arch anthropologist had shown that these apes were starving because. they develop these like tree rings or striations on their teeth associated with seasonal starvation. So there was a, I was reading about this and I was thinking, you know, maybe the mutation might have occurred right during that time when these apes were starving. And is it possible that the mutation could have been a survival mechanism to make fructose more powerful in its ability to cause fat? because we had this evidence that if we lowered uric acid,

even that, I mean, that uric acid was helping to drive how fructose was causing obesity, and so that if the uric acid went up, it might allow for increased fat stores. And it turned out that there's a famous anthropologist, Peter Andrews, at the Museum of Natural History in London, and he had been writing about these apes, and he had looked at the fossil record, And he said, actually, these European apes, before they went extinct, some of them must have migrated back to Africa and others migrated back to Southeast Asia based on the fossil record. Because it looks like our ancestors came from these European apes, not from these African apes that had stayed based on the fossils.

And so I decided I needed to reach out to him. And so I contacted him at the Museum of Natural History. I said, you know, I'm a kidney doctor. I'm studying uric acid. I, you know, I don't know much about the ancient past like this, but I would love to come over and talk to you about it. And he said, come on over. And I flew to London.

I met with him. He took me into the museum and he showed me these incredible skeletons. And it was really a wonderful day. But he pointed out that, that, you know, with global cooling, that the fruit trees maintain, because Africa was still warmer, because it was south of Europe, I mean, it stayed warmer and the fruit trees maintained themselves throughout the year so that the apes never really had to change their diet. But in Europe, where the fruit trees were, when they were slowly being wiped out, and they were, they were. were under starvation and forced the apes to leave the trees and to knuckle walk and to look for other sources of food like tubers and roots. And it was, and so they were under a lot more stress. And he had very good evidence that it was that those apes that came back that were our ancestors.

So the life, the story is such that we've posited that the mutation of your case might have happened, you know, accidentally, initially in Europe, but that the mutation would have provided a survival advantage to those apes by allowing them to hold on to fat more from the dwindling fruit supplies. And so to test that hypothesis, he and I did, we did a few experiments or a few studies with my collaborators. And one thing we did is we took laboratory animals and we blocked uricase in the animal, this enzyme that degrades uric acid. So we basically made the animal sort of like a human in terms of this mutation. And we found that when we did that, that we could give them even small amounts of fruit and they got metabolic syndrome. So our fruit dose,

that they responded very dramatically to the fruit dose. And then what we did is with Eric Gosser, we actually resurrected this extinct gene and then put it into liver cells. And we showed that, you know, when a human liver cell is exposed to fructose, it makes fat. But if it has the eurykase gene, it makes much less fat than when it's not there. And so what happened was that when that mutation occurred, it allowed these animals to store fat much more easily and to make more fat from the same amount of sugar. And so, unfortunately, that is what we still, we all still carry that mutation. And so what we did is I actually, I went to, I decided to study this more.

So we wanted to see how Western diet could affect this mutation. Because when this mutation occurred, it took the uric acid levels from like one to like three. And so what it did is it helped the animals to prevent starvation. But in itself, it didn't make them obese. And then what we found is that if, we fed them Western diet, now these animals, you know, now you can raise the uric acid much more. So when we went and we went and did a study on the Yanomammal Indians that live in southern Venezuela, and these Indians live on a native diet where they don't have Western foods.

They were eating, you know, they were eating some fruits like plantains and stuff and tubers and wild animals. And their uric acid is only like three or four. And that's the way our uric acid was around 1920. But since then, with Western diet, the uric acid is going higher and higher. So today the uric acid is six or six and a half. And the higher it is, the more we are sensitive to the effects of sugar. And so the more sugar we eat and turn, the higher the uric acid. So it's kind of like an accelerating circle.

And so that, I think, is playing a role in why we're developing obesity today. You know, what I love about what you explained. And thank you for walking us through that. You know, there's always that phrase, truth is stranger than fiction, right? And obviously, this is one hypothesis that's put out there, but it's a super strong one. And it's crazy to think that millions of years later, so many people are suffering on the planet. It's incredibly unfortunate, but it's also crazy to think. that that suffering is largely coming from an adaptation that led to what was centrally part of

our survival at that time. But because our external circumstances have changed so much through the industrialized movement, industrialized food movement, especially, that now we kind of are lost in the swamp of just high uric acid levels that are just wreaking havoc on our system. And the other thing that I think is very interesting about that, especially the study that you did with that tribe, I believe you said in South America, is that this would also be part of what explains that human beings can accelerate and do well as or modern day Hormosapians and all the different hunter-gatherer tribes that have been on earth. And the tribes that are still on earth that are out there, you see some that you see some that do well on a higher fat diet. You see some that do better on a higher carbohydrate diet. And it does seem to be from hearing what you just shared that largely is if we're sticking to a whole food diet and not having

refined carbohydrates and high amounts of fructose that come from liquid sugars that are there or unnatural amounts of dried fruit or high concentration of fruit in the diet that human beings can do well on a lot of different diet. But it's the industrial. industrialized layer that's placed upon it that will make all of those diets turn into something that doesn't end up working for us. Is that a summary that you think of? Yeah, I think that's right. So basically there's a story. It's called the Thrifty Gene Hypothesis, and there's a guy named James Neal who pointed out that that obesity and diabetes today may relate in part due to the fact that when we were in trouble, we developed genes that increase our risk for

obesity. And so we've gotten those genes. And then what happens is then we get exposed to a diet of processed foods and refined carbohydrates and all these things which actually activate this pathway further. And so what happens is we've gone into overdrive. So what was originally meant to help us survive, unfortunately, is now being in overdrive and is causing obesity and diabetes and high blood pressure. And a lot of it is, you know, we've learned how to make a junk food and so forth that's so rich in sugars and so rich in salts and so forth that it can get us into trouble. Now, we've talked a lot about as we wind down here because we have plenty for a part two. There is a few things that I want to make sure we cover that you shared earlier that I think are

takeaways within the context of your research and your work and your forthcoming book that, again, it's in the show notes. And I highly recommend that our audience pick it up. And that is that fructose is one pathway that can lead to elevated uric acid levels. But there's also other pathways that are there. I remember watching this documentary on Japanese sumo wrestlers. And for them, gaining and putting on mass is a whole art and science. And it's not actually that easy to do.

And when they were talking about, they basically have these dormitories that if you want to become a professional sumo wrestler, it's like you have to go to like sumo wrestler school. And in addition to training, you have to eat the diet. And a big part of their diet is, in addition to the quantity that they're eating in a day, they have a good, you know, when I say a bowl, it's probably not a traditional American, you know, bowl. It's a much larger bowl. They'll have multiple servings of rice in a day, sometimes six to eight large bowls that are there. In addition to that, I saw something that was really quite interesting is that they drink beer right before they go to bed at night because they have found that having alcohol, especially beer,

is something that helps them put on more mass and weight comparatively to not having that. So tell us, what is it that the sumo wrestlers know about alcohol that we all should learn and take away in our own life? So it turns out that when we identified this survival pathway that's initiated by fructose, that there's a, we found that there was this uric acid generation and that the uric acid then triggered a lot of the survival switch. And so we found that there are a number of foods that make fructose in our body as well as the fructose we eat. So those foods can also cause obesity, but we can also bypass the fructose part of the pathway by coming directly in with the uric acid pathway.

And the most effective way to do that are to eat purine-rich foods that are used to generate uric acid. And a lot of them are what we call umami foods, believe it or not. And although I, you know, a lot of us love umami, if you eat huge amounts of umami, you can actually induce, or large amounts of umami foods, you can induce obesity very easily.

And we just had a nice paper and a very good journal on this, showing how umami foods can drive obesity. The number one umami food that dries obesity is beer. And the way beer works is it, first off, alcohol will activate this pathway. And when you drink alcohol, it actually generates fruit dose as well. And that's a whole story in itself we can talk maybe more about next time. But in addition for alcohol stimulating fruit dose production in the body, beer is particularly fattening because of the brewer's yeast. And the brewer's yeast is an incredible way to raise uric acid.

It's like one of the most effective ways. And when you drink beer, uric acid goes up in your blood within a couple hours. And that uric acid is activating this pathway. So the beer belly, beer is like famous for, you know, causing a beer belly. It's a raises triglysteryzing the blood. It raises blood pressure. It causes fatty liver. Beer is another way to activate the switch.

And actually beer and soft drinks are equivalent. equivalent in their effects. Sugar is a much rapid way of doing it. It works within minutes in terms of activating the switch. Beer does it, you know, over hours, but they both do the same thing. So this idea, if you're a similar wrestler and you want to eat a lot of food, but with things that can activate the switch, and I can't think of anything better than, you know, rice, sugar, and alcohol and especially beer. These guys know what they're doing. They're experts.

And beer is the biggest one, but obviously, you know, we know that alcohol is not a health food. And a lot of people, as they become more and more aware of alcohol, they start to notice different reasons to severely limit it. Based on your awareness of the research from your sliver of the world when it comes to uric acid, fructose, the whole combination, is there. recommendations that you give to people who ask you. I'm sure your friends ask you all the time, like how much alcohol is okay, how much is not okay. And of course, this is in the context of,

you know, there's a whole, there could be family history of addiction. There could be a lot of things where people just really should avoid alcohol completely. And again, alcohol is a neurotoxin. And so it's not a health food at all. And everybody's trying to figure out, okay, if I don't have a family history of addiction, if I'm not suffering from addiction myself, I want that occasional glass of alcohol here and there that I have socially. What are your recommendations, or do you just tell people to steer away from it? Well, you know, when I was originally studying this, I kind of went down the classic route that said that, you know, one drink a day or even two drinks a day is probably fine. And it was based, especially if it's wine. Hard liquor is obviously

especially, it's commonly mixed with sugar. And it's, you know, very, you know, very, you know, very concentrated. And I, you know, I've never really been a big fan of the hard liquor and beer, I've known for a long time, really activates the switch strongly. So I was always kind of hoping that wine would be the acceptable pathway. And so I was, you know, some studies that suggests that one glass of red wine does not, you know, may actually be the equivalent to no glasses of wine in terms of its effects on health. And two, two glasses of wine. And two glasses of line sort of neutral as well, but when you get more than two glasses of wine, you're in trouble. What's happened in the last few years has been our discovery that, and it was also by another

group, that when you drink alcohol, that the alcohol can also be converted to fructose in the body. So it can become another source of sugar. And we can actually, if we block fructose effects, what happens is it's fairly dramatic. We can block the effects of alcohol to cause fatty liver. So the way alcohol causes liver trouble, it looks to be like it's driven in part by the fructose that alcohol induces. Not only that, it turns out that if you block fructose metabolism, the craving for alcohol is also reduced. So alcohol and sugar turn out to be very, very, very linked. And they converge on how they metabolize, and they both end up activating this very same switch that I'm talking about. So it turns out that alcohol probably is another

way to activate the switch. And so it's probably better not to drink alcohol than to drink it. But, you know, many, you know, if you're going to drink alcohol, I would recommend wine over hard liquor or beer, and I would try to keep it down to one drink, you know, an evening kind of thing. There's so many people that love wine and alcohol. It's a tough one. But sadly, it does activate this switch to some extent. So it's not, if you're trying to lose weight, it's probably not an ideal thing to continue

while you're trying to lose weight. Yeah, not to mention its impact on the brain. We've had other experts on the podcast before that say, you know, even recommend limiting alcohol to about four ounces a week based on their work and research in the space of Alzheimer's. And it's a tough thing, but hey, we want to look at the truth around all aspects. And I think that anybody who is drinking on a regular basis, even if you're at that glass a day and it's super high quality wine,

I think it's very important to integrate some aspect of regular alcohol fasting, long periods, maybe even a month, you know, a month on, a month off, because we sometimes don't know the full impact that alcohol is having on us. And it's only until we go completely off of it that we notice the difference that's there. I think you're absolutely right. And I haven't really studied that, but that makes a great feel sense to me. Let's talk about another category that you hinted out earlier, and that is beef. Why is beef in this category?

You know, especially in the explosion of a lot of awareness around grass-fed meats, a lot of folks have talked about grass-fed beef being in the category of, you know, even a potentially like a superfood. So what do we know about beef in its role and red meat specifically as the category when it comes to your work and research? Well, so red meats can raise uric acid. You know, it's a little bit variable, but they contain purines that can be degraded down to uric acid. There are some studies that have linked red meat intake with increased risk for diabetes.

It's a little bit of a controversial area. You know, obviously it's not like a high carb diet. where for sure high glycemic carbs increase the risk for diabetes. But there are some data suggesting that red meats may not be that helpful, healthful. And for example, there's a substance called T-M-A-O, which can be generated from red meat intake that is thought to may potentially have an increased risk for heart disease. So, you know, I'm not really a major league against red meats.

You know, I definitely understand the paleo diet and its benefits. I think the benefits of a high protein diet is primarily because you're removing, reducing the carbs rather than increasing the protein, but you definitely want to have. you know, a 25% to 30% intake of protein in your diet. That's, I think, very good. But I think that, you know, also there's issues of beef with CO2 generation and the greenhouse effects and effects on climate that I think they're potentially overcomable. But I do, I'm not a major fan of.

of red meats because of the potential to increase uric acid and some of these other issues, I do tend to favor fish and poultry. But, you know, it is not a major area of my research. Most of my research is focused on carbohydrates, salt, fat, and things like that. So what are your thoughts, Drew? Tell me. Well, I think that when you go on Dr. Mark Hyman, podcast. I think you guys will have a fascinating discussion on that on the CO2 side, because he's a lot

more of an expert in that world. And I always like to get different people's perspective. Me in particular, I've lowered the amount of red meat that I've had over the last few years, primarily because I've seen that saturated fat increases an endotoxymic, endotoxemia response for people who have challenges with their gut health and leaky gut. So that was happening for me. doesn't happen for everybody. I think there's a lot of benefits that come, you know, that you can get from, especially grass-fed, you know, beef that's out there, especially if you're including some high-quality organ meats that are there. And I know organ meats are, you know, a little bit of a challenge in your world because they have a high content of purines, is what I've read, that are out there.

So I think the big key for me is, as I was reading about your research, is that if you're eating a lot of these food categories, starting first with fructose, and fruit sugars, dehydrated fruit, and then you're having liquid forms of drinking sugar. Then on top of that, you're having a decent amount of alcohol in your diet. That's kind of like the base and refined sugars, because even if there's a high amount of glucose, you're converting that glucose to fructose in the body. That's usually the base. That's like a big base of a lot of people's diets, is these fruit sugars, refined carbohydrates.

then it doesn't matter what else you're eating, even if you eat healthy, it's kind of like downhill from there. And even if you think you are eating healthier things, but those things are high in purines, like red meat, like sardines and anchovies, potentially organ meats, you may not be getting the beneficial side of those foods

if the base of your diet is these refined carbohydrates and liquid forms of sugars. So I think the first thing, like many things, and I think whether somebody's plant-based or not, We were talking about our mutual friend, Dr. Casey Means, who's the chief medical officer at levels, you know, and you were recently on their podcast. We'll link to that too. You know, she does more plant-based.

And I think the thing is that as long as you clean up the base of your diet, a little bit of these foods here and there that you have based that are personalized for you, your body type, your background, your health goals don't seem to be as much of an issue as long as you're getting all the beneficial vegetables that are low glycemic that are in there. Yeah. Actually, you know, when it comes to us kind of viewing the overall nutrition pathway, all the different types of food, I agree with you, sugar, high glycemic carbs. These are the two major groups that I think are driving, you know, obesity. I think that there's some evidence that red meats aren't not as good as some of these other, like other meats. I think that there's evidence that's Salt actually plays a role in obesity. Yeah, talk about salt.

You know, we were going to do a whole deep dive, but just give it top level, since we were talking about a few different categories, you know, you have a unique take on salt. Yeah, so it turns out that salt, you know, when you eat, salt doesn't have any calories. So usually when we think of salt, we think of, oh, you know, we need to restrict it because it can raise blood pressure. And actually, it's true, a high salt intake, especially. if the kidney isn't able to excrete salt can increase the risk for high blood pressure. And not in everybody because you have to have the kidney has to have some issues with excreting the salt to really see that rise in blood pressure. But salt, you know, we think of as has not,

we haven't usually thought of it as playing a role in fat or obesity or insulin resistant. But when we discovered that the body can make fructose, we started looking at what is known, what are the known mechanisms for stimulating fructose production? And one of the things that can do that is if the salt concentration in your blood goes up. And so when you eat salt, the salt concentration in the blood initially goes up, that stimulates thirst, and then you drink water to correct that. And so we knew that when the salt concentration goes up in the blood, that fructose is made. So it made us realize that a salty diet might actually be a mechanism for generating fructose in the body.

And it's particularly like if you're eating carbs. So like French fries, the salt in the French fry then helps stimulate the conversion of the starch in the potato to fructose. It's like a combination hit. You eat the high glycemic carb with salt, and that's going to markedly amplify the ability to make fructose. And so what we did is we started. First, we reviewed the literature, and we found to our surprise that people who are overweight tend to eat a high salt diet, that people who are overweight tend to have a high salt

concentration in their blood, that people who are overweight tend to have the presence of a hormone in the blood that's associated with high salt concentration and with dehydration, and that's called vasopressin. And so people who are overweight or obese or have metabolic syndrome tend to be on high salt diets. They tend to be slightly dehydrated because the salt concentration goes up in their blood, and they tend to have this. And then there's studies that show that if you have a high salt on a high salt diet, that it actually predicts the development of obesity. So we think, thought, oh my gosh, could salt be an unrecognized cause of obesity? So what we did is we took

animals, we put them on a salty diet. And, you know, initially the first two months, nothing happened. And it was like they did not really show much difference from the control animals. But beginning around the third month, suddenly they started gaining weight. And by the fourth month, these mice were huge. They were fat and rotunded, and they had metabolic syndrome. And when we looked inside, then we found that they were making a lot of fructose from the food they were eating. So even though they weren't eating any sugar, they were making sugar. And then what we did is we did the high salt diet in animals that could not break down fructose, and they were completely protected. They ate the same amount of salt, but they did not get overweight. And so we realized that salt was another cause of

hypertension, but it was not the, it's not really the salt per se. It's the fact that salt makes the body act like it's dehydrated. It raises the salt concentration. So if we gave salt with water so that the salt concentration in the blood didn't go up, we could block obesity as well. So when you eat salt, when you're eating salty food, you're triggering the production of fructose, just like when your blood glucose goes up with the high glycemic food. So we have the glucose monitor that tells us, you know, that our glucose levels are high, we're making sugar, we're activating this switch to get fat. But every time we eat salt, there's nothing to tell us until we get thirsty. And at that point, we've actually activated this switch.

So then we, and so we did a study with people where we gave a salty soup to raise their salt concentration acutely. And when we did that, their blood pressure went up. But if we gave the salty soup with water so that their salt concentration did not go up in their blood, even though they ate the same amount of salt, they blood pressure didn't go up. So it turned out that the way salt works is not from the amount. it's if you eat a lot of salt without drinking a lot of water. And what happens is that triggers the animal, or in this case, us to think we're dehydrated.

And that makes us want to put on fat because fat is the source of water for the animal. When you burn fat, you produce water. And that's why animals in the desert have a lot of fat like the camel, because it's dehydrated, so it stimulates fat. It wants the fat to provide a source of metabolic water. And so it puts it on its hump so that the fat doesn't spread over the body where it would cause overheating. So, and that's why the whale has so much fat because it doesn't drink seawater. It has to have the fat to make fresh water.

And so it lives in this salty environment, the sea, and that helps drive the fat, production that it then uses to help survive. So it's all part of the survival mechanism. When we eat salt, we're creating that same alarm signal, but it's creating, quote, dehydration instead of starvation. And that's activating the switch as well. So there's two major foods that are driving obesity. One is sugar and fructose generation from high glycemic carbs. And the other is salt, which creates dehydration, and that also stimulates fruit dose production and drives fat. And then things like meats and beer, they come in also through their ability to stimulate uric acid. They can also do it. So all these foods do it to some extent, which makes it a challenge

to figure out how to block the switch and how to restore health. But it's possible, believe that. There's because there are foods that are good and their foods that are bad, just as you say. Well, you know, one point that I want to make on salt before we go ahead and conclude is that if we look at the vast amount of sodium that's in people's diet in America today, it's coming not through the salt that they add on their own food that they make at home. It's coming from ultra-processed foods. So it's salt in those categories. So just so anybody who's listening who loves a little bit of the sea salt on their, on their fish or grass-fed meats or, adds a little bit of sea salt to their salad here and there, largely, unless if somebody's

really piling on a lot of salt, which in most cases would be unappetizing. You wouldn't want to add that much salt. It's that we've been hijacked. Our taste buds have been hijacked with these ultra-processed foods that we eat that have the sodium sort of disguised in. Is that what you've seen through your work? Oh, for sure. Like, you can go, they also, like, will inject salt water into like shrimp and stuff to make them big and look big. Chicken as well. Yeah, yeah. So you go to the marketplace and you see these shrimp that have been, you know, colored with,

there's like an artificial color to make them look good. And there's, they've been injected with salt water to make them look big. And then you go home and you cook them and then they shrivel up. They shrivel up. And the salt's in there still. And, yeah, no, this is a real problem. Processed foods is a major source of salt and also a major source of sugar. It's often in the processed foods as well.

Now, if we're mostly cooking at home and we're eating a whole foods diet, which is really the solution around a lot of this. And we're avoiding the refined carbs. We're avoiding the refined sugars and the concentrated sugars that we talked about earlier, which naturally means that we're most likely going to be avoiding the high concentration salts because we're not eating those foods as the base of our diet. A little bit here and there, people can eat whatever they want. But as the base, the base means what is 90, 95% of what you eat on a daily basis. Is there what you would recommend as an upper limit of how much sodium somebody would have in a day?

So it depends on your exercise level and how much like you're sweating and your balance. Now, the average person, I think, you know, four to five grams of salt a day, is probably the right number. But, you know, it just depends. If you're a person who likes to exercise and I recommend exercise, you know, and you're sweating a lot, you're going to have to probably eat more salt than if you don't exercise. And one of the tricks is to make sure you drink plenty of water.

Our work clearly shows that the very powerful effect of hydration, drinking water, it can help reduce the risk for obesity and diabetes and keeping, you know, preventing yourself from getting dehydrated and activating the switch is really important. If you're going to eat salty food, drink water during while you're eating the food and try not to get to the point where you get thirsty because once you get thirsty, you've kind of activated the switch. And I think that every meal should begin with the glass of water in front of you and you drink that water first and then you eat. And we should probably be drinking a glass of water between meals as well. I think water is an understated

and incredibly important way to stay healthy and to keep to to help reduce obesity and diabetes and all those things that we want to avoid. Dr. Richard Johnson, thank you so much. much for coming on. I have a list of our next round for round two. I have another 30 questions that we're going to get into at that time. And I'm sure we'll pull some more from the audience as well. This has been incredibly fascinating. I'm so thankful for researchers like yourself who are not just connecting the dots, but also turning into practical takeaways. Because for the average person that's listening to this podcast, you know, you're interested in the health topics. You're looking for guidance, but we don't have the ability to necessarily.

always process through the research and the science. And we definitely don't, most of us don't have the ability to do the science on our own. So we're really reliant on individuals like yourself to do that and then connect the dots. So I applaud you on your work. I'm excited for your book to be out there and for people to get it and they can find in the show notes. And I'm thankful that we get to have you back for a round two to go even deeper. Thank you so much. It was a real pleasure.