Dhru Purohit Show - Why Excess Added Sugar is Driving Modern Diseases and How to Take Back Our Metabolic Health and Overcome a Sedentary Lifestyle

Episode Date: June 2, 2025

This episode is brought to you by Cozy Earth and Ollie. Sugar is everywhere in the modern diet, and it's silently driving a massive wave of chronic illness. From insulin resistance and fatty liver to cognitive decline, the overconsumption of ultra-processed, sugar-laden foods has created a health crisis hiding in plain sight. As scientists uncover deeper connections between sugar, metabolism, and brain health, one thing is clear: this isn’t just about cutting calories—it’s about changing the way we eat to protect our long-term well-being. Today on The Dhru Purohit Show, we’re bringing you a special compilation episode featuring Dhru’s conversations with top experts on the connection between insulin resistance, fatty liver, and Alzheimer’s disease.  Dr. Robert Lustig shares the impact of added sugar on mitochondrial health and metabolism. He also discusses what you can expect when significantly reducing the amount of added sugar in your diet, why the quality of your calories matters, and the fascinating ways our bodies store fat.  Dr. Richard Johnson discusses his revolutionary new hypothesis on the link between fructose consumption and Alzheimer’s disease. Dhru and Dr. Johnson discuss the evolutionary mechanism behind fructose metabolism, insulin resistance, and weight gain, which has backfired due to its overconsumption. In this episode, Dhru and his guests dive into: What is leptin resistance (2:11) Thin on the outside, fat on the inside (TOFI) (5:55) The three sites of fat deposition in the body (6:47) Key findings from the SHINE study (17:03) The Metabolic Matrix: feed the gut, protect the liver, and support the brain (21:35) Dr. Johnson’s hypothesis on the link between Alzheimer’s and fructose consumption (25:05) The origins of Alzheimer’s: what’s happening in the brain (33:28) Uric acid as a driver of fat accumulation, and its connection to gout, obesity, and other diseases (31:13) The relationship between salt, dehydration, and fructose production (45:51) How fructose increases our cravings for sugar (50:01) The role of fructose in Alzheimer’s disease (56:56) Also mentioned: Full episode with Dr. Robert Lustig Full episode with Dr. Richard Johnson This episode is brought to you by Cozy Earth and Ollie. Right now, get 40% off your Cozy Earth sheets and sleepwear. Just head over to cozyearth.com/dhru and use code DHRUP. Want to give your dog the best in clean eating? Take the online quiz and introduce Ollie to your pet. Right now, Ollie is offering 60% off your first box of meals when you subscribe today! Just head to Ollie.com, use the code DHRU, and you’ll get 60% off your first box of meals in your subscription.Sign up for Dhru’s Try This Newsletter Learn more about your ad choices. Visit megaphone.fm/adchoices

Hi everyone, Drew Brod here. We all know that sugar can be a huge driver of weight gain and chronic disease, especially when it's tied into excess calories. But the truth is, as we're all starting to learn in this nuanced world, sugar itself is not the enemy. It's when we eat it in the form of added sugars tucked into over 60% of the ultra-processed foods that make up the modern, especially American diet that we run into problems. I'm talking about the added sugars, that big food mixes into everyday foods like salad dressing, pasta sauces, and protein bars, just to name a few.

And our overconsumption of added sugar in our diets, in excess, huge levels of metabolic diseases, including, as a lot of experts on my podcast have talked about, insulin resistance, fatty liver, and there's even a strong argument to be made that there's a connection to Alzheimer's disease. So on today's episode, I talked to two experts on the podcast about the links that are there between insulin resistance, fatty liver, and Alzheimer's disease. First off, we have Dr. Robert Lustig, a neuroendocrinologist with an expertise in metabolism, obesity, and nutrition. In our conversation, Dr. Lustig breaks down the ways that sugar acts as a metabolic disruptor. In our conversation, Dr. Lustig breaks down the ways that excess sugar. That's the key, excess sugar.

we're not fearmongering sugar in general, especially from whole foods, but excess sugar and how it acts as a metabolic disruptor, damaging the liver, disrupting hormonal signaling, and over time laying the groundwork for cognitive decline, especially when you add on top of the excess sugar a sedentary lifestyle. He also explains the fascinating ways that our body stores fat. And I'm also speaking with in today's episode, Dr. Richard Johnson, a professor of medicine at the University of Colorado, Denver, who is internationally recognized. for his seminal work in the role of fructose and obesity, diabetes, and now even potentially Alzheimer's disease. But first, let's listen into my conversation with Dr. Robert Lustig.

Lepton resistance. The inability to see your leptin. The higher your sugar consumption, the more your insulin resistance. The more your insulin resistance, the less well your brain can see its leptin. The less well your brain can see its leptin, the more your brain thinks it's starving. And the more you'll eat those calories. So you can get your calories down not by starving yourself, not by dieting and caloric restriction. You can get your calories down by getting rid of the insulin resistance, which means getting rid of the sugar because that's what caused the insulin resistance because it's the fat in your liver that led to the insulin resistance because your pancreas makes insulin to make the liver do its job. And when you've got the fat in your liver that the sugar caused, now your panc- liver doesn't do its job.

Now your pancreas has to make extra insulin. Now you've got insulin resistance. Now you've got high insulin levels at the brain. Now your leptin doesn't work. So all those extra calories you're eating is because your brain doesn't see the leptin because of the sugar you ate. Fix the sugar. You'll fix the calories too.

But it doesn't work the other way around. So it's not about the calories. And I'll be happy to debate anybody who says it does. So as a byproduct of this, you would also say that somebody could have their calories within range. They could even be at their sort of match between their general day-to-day energy expenditure and their calories. But if we look at their labs and their fasting insulin, that could be. really high. Could be.

Even if their calories are within range. So there is a phenomenon, which I think we talked about it the last time I was on the podcast. It's called Toffee, T-O-F-I. Thin on the outside, fat on the inside, real medical term, 1,500 bedline citations coined by Dr. Jimmy Bell, neuroimager at University College London. You can be thin sick and you can be fat healthy. 20% of obese people are fat healthy.

Now, 80% are fat sick, I agree. Okay, no argument. Do you say overweight? Is a risk fact. Do you say overweight or obese? Obes. Obes. Obes.

So that is significantly, that's like, you know, I don't know in terms of BMI, but you're talking about. BMI over 30. BMI over 30. Okay. So 20% of obese people, though, are healthy. From a, from like your typical metabolic labs. from the metabolic labs and for the diseases of metabolic syndrome, type 2 diabetes, hypertension,

dyslipidemia, cardiovascular disease, cancer dementia, fatty liver disease, polycystic ovarian disease. The diseases that are killing Americans, 75% of health care dollars are due to metabolic syndrome diseases. That's sugar drives. So 20% of those people that are obese, they still could be healthy. Absolutely. Conversely, 60% of the normal weight population have the exact same diseases as to the obese. Normal weight people get type 2 diabetes, hypertension, dyslipidemia, cardiovascular disease, et cetera, et cetera, et cetera.

Okay. Now, they get it at a lower BMI. So it can't be the obesity because they're normal weight. They're below, the BMI is below 30. Okay. They're thin sick. as opposed to fat healthy. So just because you're thin doesn't mean you're healthy

and just because your fat doesn't mean you're sick. So there's this thing called Toffee. So my question to everyone is listening to this podcast right now, look at yourself in the mirror and ask yourself the question, am I a Toffee? And generally, you know, a lot of people wouldn't know this, but what body fat percentage would that be, right? Well, it could be very little body fat percentage.

Depends on where the body fat is. You're talking about abdominal body fat. No, I'm talking about liver body fat. Liver body fat. Which doesn't that typically, isn't that correlated with the abdominal body fat too? Usually, but not always. Like you see a lot of Indians and South Asians that are toffee. Usually, but not always.

Not always. That's usually, but not always. So here, there are three fat depots in the body, three. Okay. And they contribute differentially to disease. This is very important. Fat Depot number one. subcutaneous or big butt fat as in does this bathing soup make me look fat? Never answer that question.

Total loser. Okay. Guaranteed. Okay. Now, here's the question. How many pounds of subcutaneous fat do you have to gain before you get sick? Ooh. I'd love to know. About 22 on average. 10 kilos. Before type 2 diabetes and other things comes in. Exactly. Okay. Okay. 22.

Now, why so much? The answer is because subcutaneous fat does not drain into the liver. Subcutaneous fat drains into the heart. So when subcutaneous fat accumulates, the border of the fat vacuble in the fat's. cell starts to break down. The grease gets spilled. The macrophages come in to clean up the grease. They release the cytokines. The cytokines then circulate in the peripheral bloodstream, which is 6 liters. And so the concentration doesn't go up very high. And so the liver doesn't see a very high concentration of these cytokines. And it's the concentration of cytokines that the liver sees,

that determines whether or not the liver gets sick. So about 22 pounds. All right. Fat Depot number two, visceral fat, belly fat. And the fat between organ systems. Yes. Yeah. The visceral fat.

It's cool. How many pounds or kilos of visceral fat do you have to gain before you get sick? I would guess it's probably less than 22. Five. Five. Maybe six. Okay. 22 for subcufat because it drained into the general circulation. Five or six for the visceral fat because it drains into the portal vein.

The portal vein goes straight to the liver. So if your visceral fat accumulates and you start breaking down that fat vacuole and the grease starts spilling and the macrophages start coming in, okay, those cytokines are going to be get much higher concentration because they only have to populate the portal system, the portal vein, from the gut to the liver. There are two portal systems in your body. What's a portal system? What's a portal system and also what is draining? Like what is actually draining? Exactly. So that's right. What does it drain? So normally the way blood goes in your body, it goes, heart aorta artery organ vein veniceva heart okay that's called a systemic circulation a portal circulation goes like this heart heart aorta artery one organ one

Artery 2, organ 2, veniceva, heart. So the blood has to go through two organs to come back to the heart. And there's information being carried from organ 1 to organ 2, which tells organ 2 what to do. So there are two portal systems in the body. One is the hypothalamus to pituitary. We know why that is, because that runs all the different hormonal systems of the body. And the other one's pancreas to liver. Because the liver is the primary target of insulin action. And so when the liver gets fat, the pancreas has to make more insulin to make the liver do

its job. And because the liver gets fat and because it's at the end of that portal system, the liver doesn't have to get very sick for the pancreas to start making extra insulin and causing problems. Now, the question is. The question is, where did the visceral fat come from? Did it come from the diet? No.

People think that belly fat is from the diet? No. This is the big mistake. Yeah, where does it come from? Stress. And the reason we know that is because you can take people who are chronically depressed, who are suicidal, who basically have to be admitted to the hospital to keep themselves from kill. killing themselves. And you put them in a scanner and they're not eating. And so they're losing weight,

hallmark of depression, losing weight. And their subcutaneous fat is going down and their visceral fat is going up. They're losing weight and their visceral fat is going up because cortisol, the stress hormone, is the driver of that visceral fat. So would you say that for most people that are dealing with belly fat, stubborn belly fat, that stress is the primary driver? Absolutely. I guess where that's a little bit where I'm trying to contextualize that is that those people also probably the vast majority are also still consuming extra calories.

Of course. Because that's one of the treatments for stress is overeating. So you could say that you could potentially create a control experiment where you had people losing weight, you stress them out to such a degree that the cortisol is increasing in their body and their belly fat goes up. This episode is brought to you by cozy earth because great sleep starts with how you wind down. Let's face it, we're all juggling a lot. Whether it's a pack schedule, constant deadlines, or just the chaos of everyday life, finding calm can sometimes feel a little difficult. That's why I've been leaning into small rituals that help me and my wife feel

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40% off site wide. Just go to CozyEarth.com slash Drew and use the code Drew P, D-D-H-R-U-P at checkout to grab the discount. That's Cozy Earth, C-O-Z-Y, Earth, E-A-R-T-H-E-R-T-H-R-U, and use the code D-H-R-U-P at checkout to grab the discount today. Trust me, this is self-care that pays off every single night. So we did the opposite at UCSF. We did a study where we took patients with exactly that situation and taught the mindfulness. So, yeah, can you explain what that study was? Well, my, so it's like, what was the condition? It was called the shine study. Were you controlling for what they eat or anything else like that?

We took postmenopausal women and we basically taught them how to meditate. Uh-huh. So you weren't, you weren't controlling their food or anything like that? We didn't touch their food. We didn't touch their food. We only taught them to meditate. But we studied them before and six months and 18 months later. And when you say studied, what were you looking at?

We were looking at their fat depots. And cortisol as well? And cortisol and cortisol and all. also insulin and insulin resistance, exactly. And what we found was that weight didn't change that much. But in the mindfulness group, their belly fat went way down and their insulin levels went way down. Could that also be just asking,

is that also a byproduct of you've lowered your stress, you're doing less sort of stress eating and coping? And so naturally you're sort of adjusting and not reaching out for sugar and processed foods. Exactly. So you're not saying that calories wasn't a part of the equation. But they didn't lose weight. They didn't lose weight.

They didn't lose weight. But there was an adjustment in where that weight was distributed? Exactly. And that correlated with improvement in their metabolic health, unrelated to weight. Another reason why this is not about calories. You could have a situation where somebody's body composition is adjusting, right? So they don't lose weight, right? Like I've, you know, I get caliber tested every couple weeks as part of my working with this trainer.

And it's part of my goal having turned 40 and making sure my lean muscle mass stays strong. Right. But that I still do it without, you know, but keeping my fasting insulin low, keeping my glucose balanced. So my body composition is adjusted sometimes where my fat percentage is going down. You can see a little bit more of my abs. Right. But my lean mass is going up. Right. And you measure that on the scale.

Exactly right. The more muscle, the better off you are. But there could be a week where my weight kind of stays the same, but my body composition is approving. Indeed. And that's what we showed in this mindfulness study. So it's called the Shine study. It was run by Rick Hecht and Alyssa Epple, my colleague. Yeah, we've had her on the podcast before. Yes, absolutely. She was the co-PI on this. And we showed that mindfulness did not change weight. It changed health because it got rid of the cortisol, because it got rid of the insulin resistance, because it got rid of the visceral fat. Would one way to know that even the next degree, could you potentially control calories and really drive it home potentially?

Is that a possibility? Sure. I'm just sort of asking, I'm stress testing the idea because we have so many people in our audience who hear different sides of the story from different. different people. And I'm just trying to, because I have this time with you, I'm trying to ask the tough questions that enlighten us all. Right. What that would do is that would help reduce subcutaneous fat, which of course is the fat that everyone sees. Right. But it's not the fat you can see that makes you sick. It's the fat you can't see that makes you sick. That's the nugget of truth that people don't want to own up to. So the fat deposits. One was the subcutaneous fat. One was the visceral fat.

and number three. And number three, liver fat. Liver fat. So how many pounds or kilos of liver fat do you have to accumulate before you get sick? It's got to be a super tiny amount. It's got to be probably less than like, you know, a half a kilo, one pound. Okay, got it. Now, can you measure one pound on the scale?

You can. No, you can't. You can't. No, you can't. Because there's so much. Yeah, yeah. I mean, there's so much of weight fluctuation. It's in the realm of error.

Yeah. Okay, you can't. Bout movement that day, a bunch of other things. Yeah, no, you can't measure one. So people don't know that they're getting fat in their liver. Exactly. Mm-hmm. But the fat in your liver is the primary driver of that chronic metabolic disease.

Mm-hmm. And today, 45% of Americans have fatty liver disease. Considering that no one had ever heard of non-alcoholic fatty liver disease before 1980, and now 45% of an American. have it. That is the biggest epidemic in the history of the world, including COVID. And you're saying that that is driving chronic disease, but also our obesity epidemic? Well, if you become insulin resistant and your pancreas has to make more insulin and your insulin levels rise, and then that insulin works on your adipocyte, yes. Because having a fatty liver

is part of the process of somebody ultimately becoming insulin resistant? Exactly right. It's mind-blowing when you start to understand it. So, 22 pounds of subcube fat equals five pounds of visceral fat equals one pound of liver fat. You tell me which one's worst. What is the worst? I mean, it sounds like essentially what we're doing is we are creating fog raw with our entire population. We're force feeding sugar. And what do you make, what do you give to the goose to make the Guas. Corn, I believe. Well, refined carbohydrate, but you know what makes it go faster? What? Sugar. Sugar. So like what are they serving to the, to the goose to create this fatty liver that is served as a delicacy, which we call for a grot? I don't need it. They don't serve it. They stuff it.

Yeah, they literally shove it down its throat. Which is why it's considered a cruel practice. Exactly. And but what is the mixture? Do you know what they're giving them? It's a corn sugar mixture. Corn sugar. Corn sugar. So corn and sugar. Yeah. Would it have a large percentage? percentage of fructose yeah yeah that makes it the fastest and so essentially most people are doing this voluntarily because ultra processed foods are so addictive and their palate and their brain has been hijacked right and it's soft drinks that are the main lining of of that sugar so create the fatty liver that's right so we have to fix that first the and when you fix the fatty liver, you'll fix the insulin resistance. When you fix the insulin resistance, you'll fix the insulin.

When you fix the leptin, when you fix the leptin, you'll fix the weight. Which is why your classic tagline, if you could repeat it for us, starts off with protecting the liver. So let's talk about how we can all fix this. In my book, Metabolical, I basically say that in order to, you know, to turn metabolic disease around, you have to adhere to two precepts. Protect the liver, feed the gut. Six words. Protect the liver, feed the gut. Two clauses, six words. Now, the reason I did that, the reason I said that was because Michael Pollan, in his book Food Rules, said seven words. He said, eat food, not too much, mostly plants. Right.

I had to come in under that. Yeah. But would you still agree with that advice of Michael Pollan? No. No. You don't think that it gets the whole question. Michael's a friend. I've had him to dinner at my house and his wife, Judith, and they're wonderful and

delightful. I actually think that those three clauses are all incorrect. Eat food. well we just learned that processed food is not food not too much well he he doesn't consider like ultra processed foods I understood but but he does say if you can make it inside the home he's okay with french fries as long as you make it inside the home yeah but he knows that's very tough to do right but you guys still disagree he would still consider french fries food and you don't consider that if you burn the olive oil maybe not you know when you're making the french fries

not too much. Well, you know what? If you fix the leptin resistance, you won't eat too much of your own volition. You don't have to worry about it. But you still do agree generally that we don't want people to eat too much. Of course. But you guys have a different opinion on sort of the mechanism of getting there. And finally, mostly plants.

Well, don't forget Coke, Oreos, and Doritos are all vegan. So I had to come in at fewer words than seven. So I said, protect the liver, feed the gut. I lied. There are three more words. Support the brain. Right. I was going to say it's incomplete.

There's a little bit more to it. And I thought about it and I thought about it. Do I want to put this in the book? Do I want to put this in the book? If I do this, it's going to increase the number of chapters by four. And it's already 416 pages. Do I really need this? and I decided, you know what, save it for the next book.

But there's actually nine words. Protect the liver, feed the gut, support the brain. We call this now this rubric of three principles, the metabolic matrix. You know, the sad truth is that over a half of all adults in the United States are insulin resistant. And now Alzheimer's disease is being called type three diabetes for its link. to insulin resistance, type 2 diabetes, metabolic syndrome, and obesity. A new hypothesis is suggesting that another potential mechanism may also be at play, one involving fructose. And again, we're not talking about healthy amount of fruits that we all should be eating in our life. We're talking about

excess amount of fructose in our life. And to talk about this theory is Dr. Richard Johnson. and he explains how he developed this hypothesis linking fructose to Alzheimer's disease. And he talks about how he developed this hypothesis of linking excess fructose intake to Alzheimer's disease. Let's listen in. Just to talk about Alzheimer's just for a few minutes, we talked about the focus being on amyloid plaques and tau protein. And, you know, in the very beginning, everyone said, well, maybe that's the cause of Alzheimer's, these plaques. And if we can figure out how to remove the plaques or to prevent the plaques, we can treat the disease. And so much of the focus of the pharma, big pharma has been to try to develop ways to block that.

And as you have already mentioned, you know, there's been like 40 different drugs that have gone to trial and only a few have succeeded and they only work partially at best. And so people said, you know, there must be something that starts this whole disease. let's go back to when the disease is just beginning. Can we actually identify, you know, factors that seem to be important? And some of the factors that were important, you know, it's associated with diabetes and obesity, and these are diseases that I study. So I was interested in that. And it's also associated with insulin resistance in the brain.

And they do these studies where they can show that there's an impairment of glucose being taken up in the brain. if you do special scans, you can show that there's an impairment in the ability for the brain to take up glucose. It's like the brain is becoming insulin resistant. And if you wouldn't mind, we've done so many episodes on metabolic health, insulin resistance, why it's important to be insulin sensitive, but just give a little recap in the context, just in case somebody's watching this for the first time, and they may not understand, like, well, what does it mean to be insulin resistant inside of the brain? Okay, so, you know, the brain uses glucose as its primary fuel, and it loves glucose.

Glucose is the main carbohydrate that's circulating in our blood. If our glucose levels are high, we call it diabetes. If the glucose levels are low, we call it hypoglycemia. But glucose is like the primary fuel, and it's a major fuel the brain uses. But in early Alzheimer's, there seems to be an impairment in the neurons being able to utilize the glucose. There's like, you know, so insulin is a hormone that takes, that helps drive glucose into cells. And if you become insulin resistant, you have trouble getting glucose into those cells. Most of, a lot of the brain, it doesn't require much insulin at all.

And glucose can go in pretty easily. But there's certain regions of the brain that are insulin sensitive. And those parts of the brain, if you become insulin resistance, you can't deliver the fuel as well. And that's associated with the second problem that you see in Alzheimer's, which is the mitochondria are these little factories in the cell that make energy. They make ATP. And there seems to be some problems with these energy factories in early Alzheimer's. They're not making as much ATP as they should. There seems to be some stress going on with the mitochondria over time. There can be a loss of mitochondria. And so you have a problem with the energy factories. You have a problem with them taking up glucose to make energy and you have low-grade inflammation.

And I thought to myself, you know, this is actually what I study, but not in the brain, but what I'm studying in the circulation, what I'm studying in the systemic systems. You know, I'm looking at what drives insulin resistance, and I have personally linked it with energy production and inability for these energy factories to make ATP. And I thought, oh, my gosh, there's a connection there. And, you know, they were even, you know, some people call early Alzheimer's brain diabetes because of this insulin resistance, you know. And so I knew that there had to be some kind of link between those two diseases, you know,

between obesity and diabetes and people who are obese and diabetic have an increased risk for developing it. But there seem to, it isn't a match, you know. It isn't like if you're overweight, you're going to get to, you're going to get dementia. But there is this association. A strong correlation. A correlation. Yeah.

And so I started thinking about, you know, what our work shows in the body. And I started thinking about how that system might work on the brain. And I had this kind of aha moment where I suddenly realized that I could explain how Alzheimer's develops. And so, you know, it's a hypothesis. It's a hypothesis. So everybody who's looking at me, please don't see, you know, it's not like I'm saying this is the cause. But I would like to present you the evidence because it's very strong. Right.

And one of the individuals before we get to it, and this buildup is great because it's not just that we're trying to tease people before we get into it. we're actually trying to give you background knowledge of how you are showing your homework of how you arrive to this hypothesis because everything in science starts off as a hypothesis. Exactly. Right. And it's important for the audience to understand how you got there because even if the hypothesis is not 100% exactly true in the way that it's being presented, there are many instances where it could still be a big factor, the thing that we're going to get into,

that you think is deeply linked into, you know, that connection with Alzheimer's. And then with a lot of lifestyle and lifestyle factors and diet factors, there's things that we can do now where we could essentially play a little bit of a precautionary role in our life, right? Yes. If we find out that a food or an ingredient or a particular behavior, that there's not a hundred percent consensus about its link to a disease like Alzheimer's, but there does seem to be some strong links, we can say, okay, what are the pros and cons? Should we lower this ingredient in our life, right?

Yes. Should we maintain the amount that we're eating right now? Should we at least take a precautionary approach because the argument is so strong? And the downside is we might even get healthier. Yes, absolutely. If you follow some advice in this podcast and what you're presenting inside of the paper with Dale Bredesen and David Perlmutter, you know, the downside, knock on wood, is that people are just going to get healthier,

the upside is that we actually could potentially lower our risk of developing Alzheimer's. And I'm going to say one more thing. You know, the analogy that you gave about what's going on in the brain is very powerful. You know, not only is the fuel to the power plant being disrupted, but the power plant itself is not working as efficiently. That's the mitochondria.

And on top of that, there's a fire at the power plant, which is this low-grade inflammation. So all these things are going on in the brain, it's going to be a recipe for disaster. And that's what you're painting out is going on for people as they're on their path and their way to Alzheimer's. Exactly. And so, you know, just like currently, you know, people, there are different groups that are saying, okay, they've got insulin resistance in the brain. How about if we give insulin through the nose, through the nostrils, where it can actually get to the brain directly? And can we treat the disease?

Can we improve things? And there are early studies saying that might help a little bit. And there are people giving anti-inflammatories that can block the inflammation in the brain. They're seeing a little bit of protection. But the problem drew with all these kinds of approaches is they're trying to patch, they're trying to put out the fire, but they're not trying to figure out what's causing the fire. And what's fantastic about this story that I'm going to share with you is that I'm going to try to show you how it happens and how we can prevent it.

And at the end, let's talk about all the ways and the evidence that we can actually reverse or block early Alzheimer's and so forth. Because it's a very exciting area. No, it's super exciting. And so let's get into it. How do you want to start with the story? You know, you've been on the podcast previously.

Yeah. You know, we have your book in front of you here. Your last book that you wrote. It's called Nature Wants Us to be Fat. And there's a little bit of a link that's there because it goes back to your work into sort of of our origin as humans and how certain adaptations that we had in our genetics to potentially adapt to the climate that was changing rapidly around us, those adaptations helped us

survive. But the byproduct is that those adaptations in our modern life, now that we're eating so much processed foods, those adaptations are being hijacked and they're causing us to be fat. Today's episode is brought to you by Ali, the dog food. brand that treats your pup like family because they are if you're anything like me you want the best for the people you love and that honestly includes your pets as well but not all dog food is created equal most options on the store shelves are ultra process packed with fillers preservatives and mysteries that you'd never eat yourself that's where ollie comes in they deliver fresh

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box today. You're absolutely right. So we have, we have identified two mutations that have occurred in the past, both kind of interesting stories that make us more susceptible to obesity and diabetes and at the same time may also have a role in an increase in our risk for Alzheimer's. But the fundamental issue is not just those mutations, but what is this pathway that's causing obesity and diabetes? So what I'd love to do is to take you through that part. And then we can then hit the... the mutations and the survival pathway in the past as well. For sure.

It's an important part of the story and it builds up and they're both linked together. Yes. Yeah, they're both linked together. So I was very interested in what was causing obesity and diabetes and through a series of adventures and research adventures related to doing different studies. We came to the observation that uric acid, was very important in obesity and diabetes. And uric acid is a substance that circulates in our blood,

and it's like a breakdown product of energy. So when energy breaks down, energy is, we call energy ATP, and that's what we use to do everything we want. So the mitochondria, these energy factories, produce ATP, and the ATP is what gives us the animal, There's really two types of energy. There's the active energy, which is the ATP. That's for, you know, talking, running, jumping.

And then there is stored energy and stored energy is fat and, you know, can be carbohydrates too, but most of stored energy is fat. And so when a bear is hibernating and he's not eating and not getting the energy from food, he can use the stored energy or fat to produce the ATP he needs. So yeah. Fat is a battery pack that nature designed us to have. We think of it as being bad in modern times, but it was crucial in our survival because it meant energy. That's right.

So I became interested because we found that uric acid had a role in causing fat. And it had a role in raising blood pressure and causing things. So, you know, as I mentioned, uric acid is a substance circulating in our blood. And it varies. since a lot of people have low levels and some people have very high levels of uric acid. And if the levels get really high, they can cause a disease called gout. Which a lot of people are familiar with as is related to uric acid. That's how most people know about it.

That's right. They might know that their parent or grandparent or somebody, you know, their uric acid levels were so high that they were like, oh, you're dealing with gout or that individual. Typically, what are the symptoms associated with gout, you know? People often hear about- Yeah, they get this joint pain. It's basically an inflammation. of the joints. And so you get this red hot joint, typically the big toe or the knee or the ankle,

sometimes the wrist. And it's miserable. It's very, very painful. It lasts a couple of weeks. Sometimes, you know, people take medication like Advil and ibuprofen can help reduce the inflammation. But it's, you know, although people used to think of gout as just being an arthritis, there's more and more evidence that it's not. And these uric acid crystals can also go to the kidneys and go to the blood vessels. And about there's recent studies that suggest that people with gout that, you know, that they have crystals in their aorta and their coronary arteries too, you know, the majority have some crystals in their blood vessels.

It tends to go to the plaques in the blood vessels. And so gout is not just an arthritis. And it's been known for a long time that gout is also associated with obesity and diabetes and hypertension and kidney disease. And so I... It's also why, sorry to interrupt, for a long time people would call it the rich man's disease. Exactly. Because it was associated with excess and especially in our society, you know, 50, 60, 70, 80 years ago where obesity rates were a lot lower, they did see gout primarily in individuals that had access

to extra calories, which also included alcohol. And that's why they would typically sweet wines, things like that. They would typically tell those individuals to avoid those types of foods if they were dealing with gout. So anyway, so for a long time people linked gout with, you know, being a rich man's disease, also with being overweight, obese, hypertensive, all these conditions. It's about 70% of people with gout are overweight. I mean, it's like a very strong association.

60 or 80% are diabetic. I mean, it's a very strong link. And people were saying for years thought, you know, hypertension and diabetes and obesity increase your risk for gout. But actually, the high uric acid usually precedes the development of obesity. It precedes the development of diabetes. that precedes the development of kidney disease. It's one of the earliest markers

that predicts the development of these conditions. It's a very strong predictor. And when we were studying it, we realized that uric acid doesn't just form crystals and cause inflammation. Uric acid is biologically active. And one of its main things that it does is it acts on mitochondria,

those little energy factories, and it causes stress to them and reduces their energy production. Think about that. Okay. So anyway, so I was studying uric acid, and that took me to, you know, what, we had this evidence that it was driving blood pressure

and might have a cause in hypertension. And we did this study actually in adolescents who were overweight, where we lowered uric acid in them and their blood pressure corrected it. And we published it in the JAMA. It was, you know, a big deal. And that was done through medical intervention?

Yeah. We just low, yeah, we used the drug to lower the uric acid. And 90% of them were so became normal intensive. Wow. It was amazing. And they never got, they never received a blood pressure pill. And that's your area of expertise. Right.

Right. That's your background. Right. As a kidney doctor. That's right. That's really your bread and butter of what you studied in your career. So then the question was, what drives the uric acid up? And, you know, most people think of alcohol.

and actually things like red meats, but actually one of the major things that raises uric acid is fructose and sugar. And so actually, Gary Toves, who I'm sure you know, interviewed me related to a paper that was published in the New England Journal on gout and its relationship with diet. And when we were talking on the phone, he says, what do you think about sugar as a driver of uric acid? I said, well, it's definitely as a driver. It's the fructose component. And then, you know, and after I had my conversation with him, I went home and I thought,

you know, we should give fructose to animals and see if they develop high blood pressure and if we lower the uric acid, can we lower the blood pressure? Because at this point, I was focused on blood pressure. And so what happened was, you know, some people in my lab, Taka, Nakagawa, we gave fructose to animals and they became hypertensive. And so fructose is that component of sugar. So table sugar or sucrose is half fructose and half glucose. And there's another sweetener, high fructose corn syrup. It's also about half and half fructose and glucose.

But fructose is the only sugar that raises uric acid. And so we gave fructose to animals and they became hypertensive. The blood pressure was high. The blood pressure went up just like this. And we gave the drug to lower the uric acid and the blood pressure came down. But there was a big surprise because the animals got fructose also started getting fat. And they started developing insulin resistance. And they, you know, their fats went up in their blood.

The fat went up in their liver. I mean, they were developing obesity and metabolic syndrome right in front of us. And when we lowered the uric acid, we actually could reduce all of those. And I go, oh, it can't be. It can't be just lowering the blood pressure but also lowering all these other things. And then we started realizing this was that fructose was, first off, it was a very potent driver of obesity. But the other thing is we could lessen it by lowering uric acid. And the cool part is uric acid is not in the caloric pathway.

You know, so there's calories. You know, everyone says it's calories. Calories are the, yes, they're saying calories are the big driver of obesity. Right. But uric acid was being produced independently of the calories. And when we block that part, we actually were blocking, you know, the obesity. So what we figured out it was it's not so much the insulin resistance. causes inflammation. It's that fructose is driving a series of events to help the animals survive

acutely. You know, it's stimulating inflammation to help fight off infection. It's raising blood pressure to maintain circulation in a state where it thinks it doesn't, you know, that it's maybe starving. It increases pressure in the kidneys to facilitate excretion of the, you know, stuff through the kidneys. it, you know, causes insulin resistance, which is to help preserve some glucose in the blood for tissues that need it. You know, it moves, makes fat, but it blocks the breaking down of fat. And so it's stimulating all of these at once, and it's all working by through the mitochondria, and there's specific chemical pathways that are driving each one that we've been studying. So we can actually show that, you know, how the industry.

and resistance develops, how, you know, why you can't break down the fat. It's all driven through this particular chemistry. And then we realize that fructose is really the, was meant to help us store energy and prepare us for, you know, times when there's no food around. Like winter. Yes. Whereas glucose is there for the immediate fuel. And then glucose is like trying to raise the ATP in the cell, fructose is trying to get us to store fat. And the way it does it is it drops, it stuns the mitochondria, drops that ATP, and activates all those pathways. And that was the fundamental discovery. We go, oh my gosh, this is super important in evolution and biology. Glucose is really meant, has a different role than fructose. And then we realize, though, that if you eat

too much glucose, it gets turned over into fructose. And we found out that very mild dehydration could also stimulate fructose production because fructose helps the animal store water by generating fat. And then we realized that the best way to create an animal to cause mild dehydration was to eat salt. And then we started doing studies with salt. And we realized that when you eat salt and you get thirsty, you're actually stimulating fructose production from glucose. So salt activates the chemical reaction that converts glucose to

fructose. So you've got two things that are important for making fructose. One is you've got to have glucose around. So if you're on a low carb diet, you're in good shape because you're not going to have so much glucose around because all glucose comes from, you know, the main source of glucose in our body comes from the carbs. You can make glucose from amino acids and so forth, but it's not very much. And so most of the glucose that we in our body comes from the carbs wheat. So if you're on a low carb diet, you're not going to make very much fructose. That's why low carb diets are so fantastic because not only are they reducing sugar intake,

but they're reducing good carb intake that will reduce the amount of fructose you make. But salt is a very powerful way of converting glucose to fructose. And that's why French fries, for example, are so, to cause so much obesity and are so bad because you've got the carbs, you've got that starch, the potato, and then you've got it coated with salt, make it taste really good. And that salt activates the conversion of the carb to fructose, the glucose to fructose. And then you coat it with the fat, and now you've got the fat. You got the trifecta.

Yeah, you got the trifecta. So, boom. And just again, in the context of it, because, you know, right now, even though you're talking about these different pathways and how these different, either ingredients or macronutrients play a role in this, you're not totally demonizing salt. You're not totally demonizing carbs. You're not demonizing anything. We're talking about what happens when, unfortunately, in America, we're eating these highly processed foods, right? And just even if people were not eating the level of highly processed foods, that alone, like, if you're following along with this,

Like that alone, even though there's more to it, there's more to it than just this, that immediately is going to start to pull you in a direction where you're not activating these pathways as much. You're totally right. Yeah, I still eat cake on my birthday, you know. I'll eat salt, you know, I'll have salty food occasionally. It's not that, you know, that we want to eliminate these foods in any way. But what we want to do is to be aware that they can convert to fructose. And if we're doing a lot of it, we're going to generate a lot of fructose in our body. And we're going to eat a lot of fructose if we eat sugary food. So we want to cut it back.

We want to reduce it. If you can get rid of it, you know, soft drinks, that's a good move. You know, soft drinks don't do anything. Right now that's the biggest concentration of fructose. Yes, right. Especially if it's not, you know, that may have its own challenges, but especially if it's not like a diet soda or something like that. That's right.

And natural fruit turns out to be. much healthier than we think. You know, if you're a bear and you're eating 10,000 grapes, you're going to get, you're going to get fat if you eat 10,000 grapes, okay? But, you know, when you eat a natural fruit, it's only three or four grams of fructose, typically in a fruit. And my friend Josh Rabinowitz showed that the intestine inactivates about three to four grams of fructose. So you can eat a natural fruit and you won't get any fructose to your liver, you know, because it's all removed by the intestine. And it's really in the liver where it controls this metabolic syndrome.

And so if you just eat occasional fruit, you know, you're going to get all the good things in the fruit. Phytonutrients. Yeah, vitamin C. Fiber. Potassium, fiber, and all these things are good. And actually, vitamin C and flavonols and all these things, potassium, they actually counter the effects of fructose.

So we actually did studies where we put animals or people on a lot of. fructose diet and we supplemented them with natural fruits. So they were getting back fructose, but only in the form of fruit, not in the form of refined sugars. And they lost weight and, you know, they did well just as well as the people who did not get the natural fruit supplements. Right. So it's all about the context. And again, when you're eating fruit in its whole form, we'll get to fruit juice. Yeah, fruit juice isn't good. Yeah. Fruit juice, which could have some of the same problems that, you know, high fructose corn syrup soft drinks have. Talk about that.

Yeah. So fruit juice. And by the way, just for everybody was listening, we're about to get right back into all things. Yeah, we're going to get there. Exactly. We got to establish a little bit of the groundwork. That's right.

So fruit juice. So fruit juice is where you take multiple fruit, you juice it, you get rid of some of the pulp and the fiber and you end up with a drink that often has like three or four fruits in it. And so instead of having three or four grams, of fructose. Now it can have maybe have 20 grams of fructose. And now it's similar to like a fruit, like a soft drink. And, you know, apple juice. I love apple juice, but it's not good for you because there's a lot of sugar in it, a lot of fructose. And it will trigger the switch. It will trigger this activation. So I don't recommend fruit juice. So anyway, so, you know, the first discovery

was that fructose was different from glucose or from other foods that it really dropped the energy in the cell and that this and that this activated an alarm signal that triggered metabolic syndrome. The second discovery, though, was that there are other ways you can make fructose and some of them are from high glycemic carbs and salty foods. And then we realized that if you ate a lot of those foods, you could get into trouble too. And so, but it would all really be. related to fructose because if we blocked fructose metabolism, animals could eat salt and they wouldn't get fat. They could eat salty foods. They could eat processed foods, you know. And so it turned out to be fructose. And so then I, you know, we began to realize that it wasn't just activating the metabolic syndrome.

It was also it had these neural effects. So like the brain effects. So when animals start eating fructose, they actually start to forage for food. And that foraging is part of the survival response. So it actually, if you give fructose to an animal, it will start moving around and looking for food. They're hungry. They get thirsty. And it triggers a foraging response. And it was that information made me start thinking more about what was going on in the brain.

how is fructose affecting the brain? And we knew that if you give fructose to an animal or to a human and you label the fructose, only about 1% of it gets to the brain. So there had to be another mechanism. And the insight was that when you take these high glycemic foods or soft drinks, they stimulate fructose production in many sites, including in other tissues.

And so they stimulate fructose production in the brain. And there is a brilliant doctor named Sherwin at Yale who did these studies where he infused glucose in people and he could measure fructose production going up in the brain of people. And it happens like after about an hour. So if you infuse glucose, it takes a little while for that conversion to occur. But you can start measuring an increase. and fructose in the brain.

How do you get glucose directly into the brain? Like what was he doing? He was, well, no, he was given an intravenous. Okay, so it's still less so yeah, so we want to say, exactly, sir, once, and he brought the blood glucose up. And when the blood glucose goes up, we know it can converts to fructose. Right. But it will convert, tissues will start making fructose wherever that glucose hits.

So that glucose is going to the brain, but now because there's excess glucose, the tissues potentially in the brain, are now activating and creating fructose, and already you've shared with us that fructose is one of the ways that we end up poisoning the mitochondria in the cells. Right. And it also can induce insulin resistance. So now I'm going to tell you this story of how we started putting together Alzheimer's. Alzheimer's.

Let's talk about it. So the first thing is you look at what are the risk factors for Alzheimer's disease? And, you know, dietary ones, guess what they are? Eating sugar. Sugary foods has been reported to be a risk factor for developing Alzheimer's. Eating high glycemic carbs, they make fructose, right? A risk factor. Salty foods.

There are all these papers showing that high salt diets increase the risk for Alzheimer's. Right. And just one context. We mentioned this last time. But the vast majority of salt in people's diets today is coming from. from pre-processed foods. In fact, the biggest one was breads and rolls. We're not talking about the sea salt that you add to broccoli,

the sea salt that you might put in a little bit of dressing. It's the ultra-processed foods, which have more sodium than you would never put that much amount of sodium in it, but they've been designed to be super salty and kind of hidden with sweetness and fat. What sometimes they do is like they take these little shrimp and they'll inject them with salt water. Saline water, right? Yeah. And then what that does is it makes the shrimp big, looks big. Same thing with chicken.

They'll do that with. Yeah, yeah. And then people go into the market and they see these big shrimp and they go, oh, they look good. And they bring them home and then they start grilling them and then the water comes out and they shrink. Right, right. But they keep that salt in there. They'll keep that salt inside there. So now you're getting the salt, yes, processed foods.

Process food, not sea salt that we're adding to our food. They contain so much salt, so much sugar and they're associated with Alzheimer's too. Right. Process foods are in, or rich. Pasa sauce, all these things. All these things we get in the grocery store. So first off, there's this association of foods that can make fructose or that contain fructose correlate, you know, and I don't mean natural fruits.

I mean like soft drinks and fruit juice. You know, these things are associated with Alzheimer's. Concentrated forms of fruit. Obesity is associated with Alzheimer's. Diabetes is, and these are conditions associated with, you know, that we think fructose is driving. Okay. So then, so that's the first thing is there's this association. And the second thing is that if you give sugar to an animal,

after a number of weeks, they actually have trouble, you know, going through a maze. So normally you can measure how long it takes for a lab mouse to get through a maze. And each time it will get a little bit smarter and it will shorten the amount of time. to get through it. But if you feed it sugar, it doesn't show that shortening. It continues to have trouble all the time getting through the maze. And when you give the sugar to the animal and you look in the brain, guess what you find? You find suppression of the mitochondria with less, you know, there's oxidative stress to the mitochondria, which we know happens in other tissues with fructose. and it's associated with lower ATP production,

low-grade inflammation, and insulin resistance. That is the hallmark of early Alzheimer's, right? I mean, these are the exact same things. You can show exactly the same things. And then over time, if you take the animals out to like 18 weeks, and then you start seeing amyloid plaques as well as tau protein in the brain of those mice. Wow.

So that's pretty strong evidence. Okay. And so... You basically are inducing Alzheimer's. Right. In these laboratory rats. They call it an Alzheimer's model, but it's, yeah, exactly. Just fructose in the drinking.

Just by giving fructose in the drinking world. Correct. Now, here's another bit of evidence. If you take people with early Alzheimer's and there was an autopsy study done, in early Alzheimer's, they had like nine subjects. and all nine had fructose levels in the brain five-fold higher than the controls. And the, you know, control autopsy brains. You know, there was five times more fructose.

And except one of the controls had high fructose, but when they went back and looked, they decided they realized that that patient had early Alzheimer's too. So there is an association there. Okay. But here's one of the most interesting bits of data. Yeah. So if you give fructose to a human, you, well, so let's go back. I want to talk about this foraging response again.

Yes. So when animals get fructose. So when animals get fructose, they start searching for food. And foraging is a actual behavioral response. It's more than just looking for food. It involves a lot of things. First, you have to have exploratory behavior. because you're going to go out into areas we've never been,

so you have to be a little exploratory. You can't deliberate on anything very long because you've got to get in and get out, so you have to look around very quickly. You have to have good visual cues for food, you know, so that if you see that little piece of food up there, your eye catches it, you can see it, you know, latch onto that chocolate cake, you know,

that light up that part of the brain. You have to have less self-control. If you have too much self-control, you're not going to go into an area that's dangerous, right? You don't. You have to be bold, impulsive. So this is a behavioral set. In some respects, it's sort of like a hero, you know, the scout, the guy that's going to go out and try to, you know, get through the enemy lines. And, you know, I mean, there's some aspects of it that are admirable.

And I think it is an admirable response. You're willing to go out there and try to find that food. But it's a real behavioral response. So it turns out that to do that, you have to stimulate certain parts of the brain and you have to inhibit other areas of the brain. So a lot of the cerebral cortex is involved in self-control, especially the frontal cortex. So you would want to inhibit that if you're going to forge.

The prefrontal cortex, which is our executive brain. We want to quiet that down. Yes. You want to reduce the activity there so that you have the self-control is not so strong. Right. Like, is this dangerous? Should I do this? Should I not? We want to quiet that portion of the brain down to get a little bit more into sort of like crazy hero mode, ready to wrist take. Right. And you got to quiet the recent memory because you don't really want to remember how, how dangerous it really is what you're about to do. You don't want to remember that line you saw yesterday. Sure.

So you want to quiet that. You want to stimulate, you know, the visual cues, you know, so that you can see things real quickly. You want to reduce the activity to the areas that are involved in deliberation so that, you know, you want to stimulate locomotor activity. So there are some things you want to stimulate and some things you want in any help. So when you give. fructose to a human intravenously or orally, you can do this thing called bold MRI and you can do these different things where you can look at changes in blood flow. You can look at that. And guess what? If you give fructose, you activate these foraging responses. You inhibit the cortex. You inhibit

blood flow to the hippocampus, which is involved in recent memory. You stimulate the, you know, other areas, you know, like the visual cortex, the for cues, for food. And you can show that. If you give glucose acutely and you just look in the first 15 minutes, remember, it takes an hour for the glucose to start converting. So if you look the first 15 minutes, you see the opposite effects of fructose. glucose is not aiming to to make you hungry. It's to satisfy you. So it's more of it. It's a different. So it turns out that like the four, origin response requires activation of the anterior cingulate. It's a part of the brain and the occipate.

And the anterior cingulate has been uniquely known to be spared in Alzheimer's. And the visual cortex is generally spared, whereas all the areas that trictose inhibits turn out to be the regions of the brain that are specifically targeted in Alzheimer's. Especially, you know, I mean, eventually Alzheimer's will affect all the brain, but, you know, in the beginning, in the beginning, you can really show this difference. And so when I, when I presented that to Dale and to David Perlmottor, you know, they go, you know, this is pretty significant because it's not so many people have been able to explain why Alzheimer's affects one region and not another.

Right. What's going on in the body that you also see this behavior if you want to talk about it? Yeah. In often elderly patients that have Alzheimer's. Yes, they start wandering. They start wandering. Yeah. Anybody who has my grandfather suffered from, you know, dementia, Alzheimer's for years,

they forget where they are. They start looking around. They're looking. They sometimes end up, it can be very dangerous. Yes. My mom used to work at an elderly home for a period of time when we were younger. You know, they'd regularly have patients go outside, end up on the street. Yeah.

You get Amber alerts for elderly patients here. in Los Angeles all the time, who end up outside of their nursing home or sort of wandering out on their house. And in the same way, you're sort of connecting the dots that you can induce that in laboratory rats. If you feed them fructose, you can create this sort of wandering aspect. Yep. And it's partly maybe an evolutionary thing that we were designed. It was a survival mechanism. But this is kind of happening to Alzheimer's patients because probably a big part is their diet. Yeah. So, yes, so to summarize how we think of this or the way I think of this, and I have to, again, thank David Promot and Dale Bredesen and Maria Nagel. But what we think is going on is that, you know, fructose developed as an evolutionary mechanism to help animals survive. Fructose is the nutrient that helps you store energy. And it's there, it's mental. to help you. You know, it was it was meant to be a good thing. When there's very little food

coming, you want to eat fructose to store that fat, you want to stimulate foraging so you can get the food so you can survive. It's all meant to be short term and to be beneficial. But what's happened is we develop taste for foods that could make fructose, right? We develop sweet taste so we can pick out that food, we salt taste so that we can pick out the foods that tend to help put fat on us. And in a world with hunter-gatherers, in a world where food wasn't so easily available, these were beneficial, you know.

And if you, you know, and then, you know, now that we have all this high-fructose corn syrup and sugary foods and processed foods injected with salt and sugar, and we have, you know, and now that we can go to the grocery store whenever we want and we learn to crave sugar and we and then we you know we develop a craving and some people crave salty foods and and and we're eating all these foods to stimulate this foraging and all this and what's happening is we're reducing the ATP, the energy in these cells,

you know, in our brain and our muscle and it's leading to muscle wasting sarcopenia. It's leading to you know, as we lose our energy in the brain, as the cells get less ATP, they can't function as well. And then what happens is they start dying and they get inflamed and they start creating these amyloid plaques. It's kind of an inflammation and inflammatory response to the low energy state. And so that's what's going on, I think. And so the wonderful, it's not wonderful, but the wonderful aspect of this is that if we actually understand what causes it, we can design and try to figure out how to prevent it. And, you know, already groups are, I mean, Dale Bredesen has been a leader at, you know, developing healthy diets and approaches to try to block Alzheimer's.

And there are other groups as well that are doing keto diets and low-carb diets is a mechanism to try to reduce, you know, to improve the energy in the brain. And, you know, I think there's a lot of positive things coming. We've known that hunter-gatherers like the Samani, who live in Bolivia, don't really get Alzheimer's, and they're living in a very healthy environment. We know it's not natural fruits, so please, all of you, you know, we're not trying to great fruit phobia.

Yeah, I want you to continue any fruits. but but but you know dense sugars high glycemic carbs we need to reduce those we need to drink more water we discovered that you can that when you drink water you can block that enzyme that converts the glucose to fructose you can actually inhibit that enzyme by by staying well hydrated and and we could stop weight gain and so forth in animals on sugar by just drink giving them water and we did studies in people too. So drinking like eight glasses of water a day, eight eight ounce glasses is very healthy. Drinking a glass of water before you eat your meal is very beneficial. I have some water right here. Yeah, yeah. Well, while you take a sip, you know, just to connect all these dots together.

Yeah. Here you are understanding that your work in the space of obesity and what was driving things like hypertension. And you found this pathway and how uric acid was a precursor to it, but what drives up uric acid that led you to a few things, but in particular, fructose, and that led to also the conversation around mitochondria and what's damaging our ability to produce energy and what's causing more insulin resistance in the body. So we have fructose, which is a poison for that. Well, some of the same things that induce obesity inside of the body that you were able to induce obesity in sort of laboratory rats, you know now that, well, that can almost induce Alzheimer's.

Not almost. It does induce Alzheimer's, as you call it, Alzheimer's model in rats. And so now the connection and where you're calling it a theory is that this explains why something like Alzheimer's happens to certain parts of the brain, but maybe not other parts of the brain and how fructose could be a big driver of this connection. So in theory, the explosion of our modern industrialized diet that we've had over the last, what, since 1930s, around there, 40s, 50s, somewhere around there. And the increase every year of fructose, highly processed calorie, also highly processed salts inside of the diet, not, you know, sea salt and stuff that we add to our food, a little bit of broccoli, you know, grilling something or stir frying. We're talking about highly concentrated forms of salt in the food that's added into.

factory before we even get it, that these couple things, and I have a question about saturated fat, because you talked about that last time, we'll get to that in a second, that these things could be a reason why we see an explosion of Alzheimer's rates that are out there today. Yeah, I think that's right. Sadly, there are nearly six million individuals that live with Alzheimer's disease in the United States, and the number continues to rise. After 30 years of encountering dead ends while addressing all summer's disease as a problem of brain plaques in a simplified form, researchers are now exploring other contributing factors. And this hypothesis from Dr. Johnson offers some hope

to get potentially an insight, a new insight, into how we might be able to contribute to ideas and new ways of thinking that could help us eventually prevent this disease. Now, I shared this caveat earlier, but again, I want to stress it. It's important to me again to stress that we don't need to be worried about the fructose from whole fruit or the occasional glass of juice. And I'll also add that I'm not worried about some add sugar here and there, as long as we don't have crazy dosages of this everyday on top of sedentary lifestyle. That's the mixture that gets people into trouble and is driving a lot of issues in our modern world of health. The truth is, if you're getting most of your calories from whole foods,

generally staying away from ultra-processed foods and not drinking things like sugar, sweet and sodas or other beverages, on a regular, regular basis, and your focus on the basics like hydration, adequate protein, fiber, and strength training, not eating too much saturated fat, then you're going to be better than 99% of people that are out there. And if there's areas in your life and your diet where you want to make some small changes,

I hope you're walking away with today's episode, feeling empowered with the information to make those shifts. As always, if you want to learn more about anything you heard today, I recommend and encourage you to listen to the full-length episodes with Dr. Robert Lustig and Dr. Richard Johnson. And if there are people in your life who you think would benefit from the information covered today, I encourage you to share this episode with them. As always, thanks for tuning in. I'll see you next week.