Dr. David Perlmutter on Metabolic Mayhem: Uric Acid, Fructose & Your Health

This episode is brought to you by Nootopia. Nootopia is a bioptimizers company with the first ever 100% personalized nootropic stack. Think a powerful brain-specific supplement. Nootopia has been a real game changer for me. When I take one of their stacks, I get hyper-focused for the toughest tasks. My verbal fluency and creativity improved dramatically and reduced stress to boot. To say goodbye to afternoon energy crashes, boost your emotional intelligence, activate neurogenesis, and more, check out nootopia.com/claudia to receive 10% off your order. That's nootopia.com/claudia. Hello, dear friends. I'm Claudia von Boeselager, your host, and welcome to the Longevity and Lifestyle Podcast, where I invite pioneers and thought leaders in all things longevity and lifestyle to give you the strategies, tools, and practices to live better and help you reach your highest potential. Today's guest is Dr. David Perlmutter. Dr. Perlmutter is a board-certified neurologist and 5-time New York Times bestselling author. He also serves on the board of directors and is a fellow of the American College of Nutrition. Dr. Perlmutter received his MD degree from the University of Miami School of Medicine, where he was awarded the Leonard G. Roundtree Research Award. Dr. Pellmutter serves as a member of the editorial board for the Journal of Alzheimer's Disease and has published extensively in peer-reviewed scientific journals, including Archives of Neurology, Neurosurgery, and the Journal of Applied Nutrition. In addition, he's a frequent lecturer at symposia sponsored by institutions such as the World Bank and IMF, Columbia University, Scripps Institute, New York University, and Harvard University, and serves as an associate professor at the University of Miami Miller School of Science. Dr. Perlmutter's books have been published in 32 languages and include the number one New York Times bestseller, Grain Brain: The Surprising Truth About Wheat, Carbs, and Sugar, with over 1 million copies in print. Other New York Times bestsellers include Brain Maker, The Grain Brain Cookbook, The Grain Brain Whole Life Plan, and Brainwash, co-written with Austin Perlmutter, MD. He's the editor of The Microbiome and the Brain, authored by top experts in the field and published in December 2019. His latest book, Drop Acid, focuses on the pivotal role of uric acid in metabolic diseases and will be published in February 2022. It is available for pre-order widely already. In this episode, we dig deep into why the food we are eating is literally affecting the planet, from decision-making and politics to the environment, why combining medical practice with a deep understanding of nutrition is so essential for every medical practitioner, What uric acid that once helped us humans survive as a species is actually doing to our health. The metabolic mayhem pandemic and how it's destroying lives. Fructose's damaging effects. How to test for and understand what optimal uric acid levels should be. Tips on how to prevent metabolic diseases. How wearables and digital devices will create improved health and much more. Before we begin, please hit subscribe to the podcast and consider leaving a written review. I'd love your feedback, what you enjoyed and what you'd like to hear more of. You can also reach out on Instagram @longevity podcast. Longevity and Lifestyle. Please enjoy.

Dr. Perlmutter, such a pleasure to have you on today. Welcome to the Longevity and Lifestyle podcast.

Claudia von Boeselager, very happy to be with you today. Thank you.

Thank you. So I'd like to start for those perhaps not that familiar with your incredible work, that you have a very unique expertise combining board-certified neurologist together with nutrition. Where did this passion come from to combine both? That is unfortunately far too underrepresented in medical practices these days.

Well, I'm glad that you characterized it there at the end because in my opinion, this is how it should be. I don't think it's certainly limited to neurology. I think every healthcare practitioner should absolutely know about nutrition and what goes on in the human body in response to an incredibly powerful informational event, and that is eating food. And if you go to vet school, you get 2 years of nutrition. Why? Because it matters. You take your dog to the vet if it's sick, and the first thing that the vet's going to ask is, what are you feeding your dog? I've been in that experience. We had a problem with our dog. It was losing its fur. And we walked in, and the first thing the vet asked was, what are you feeding your dog? And I thought, wow, if I do that in my medical practice, people are going to scratch their heads and say, what do you mean, what am I eating? Why is that relevant for my headaches or my other neurological problems? It's very, very relevant. And my training was really about naming the problem. And it was really pretty much, as a neurologist, diagnose and adios, meaning here's your problem, good luck with that. And I just was really very frustrated by that, not only because in that regard, you're not really helping people, but ultimately, if there is any intervention, it's to treat symptoms of the disease, pain pills for headaches, etcetera. It was never to identify the cause. So we were very much treating the smoke and ignoring the fire. And when I began to get my arms around that, I began to think there had to be a better way because at that time, which was, let's say, about 25 years ago, gosh, a long time ago already, we were really seeing that there was, like, a heart-smart diet. People were talking about eating in a certain way, although what was talked about 25 years ago for the heart was way off base. Nonetheless, there was a narrative saying that here are certain foods that you should adopt if you have heart disease. We recognized even back then that the fundamental mechanisms that were causing heart disease were the very same that caused things like Alzheimer's, and that is inflammation. If we could rein in inflammation by dietary changes in heart disease, Why in the heck would that not be relevant for the brain? So I began exploring that and realized that people were researching it. No one was talking about it. And the deeper I got into it, the more it challenged my other neurology partners in my practice, ultimately to the point that it became clear that Dr. Perlmutter needed to move on. I mean, it was a mutual kind of understanding because, you know, I was talking about to people about what they ate. My goodness, why in the world would you do that? And that was something they just were not comfortable with. And, you know, to be fair, I had received zero hours of nutritional training, at least in medical school, but I had done my darndest to learn as much as I could about nutrition. And, you know, ultimately I think became fairly educated in this topic to the extent that, as you mentioned, I'm a fellow of the American College of Nutrition. So it's a powerful input. Into how we chart our own brain's destiny. And that's a lot of responsibility because, you know, in Western cultures, we're pretty much told, you do whatever you want, live your life however you choose. And when you have a problem like diabetes or your cognitive decline is obvious or you have heart disease, we'll fix it with our magic pills. Well, that doesn't really work very well. And so we have to be very preemptive, and we have to identify what's causing inflammation, what is increasing the action of what are called free radicals, you know, what is paving the way for these problems. And certainly nutrition and other lifestyle issues like sleep and exercise and stress and getting into nature are all extremely valuable tools in the toolbox. They are levers that we can pull in order to really change our health destiny, not only as it relates to the brain, my goodness, but even as it relates to our chances of having a good or bad outcome as it relates to COVID infection. We're in charge of that. It's not the luck of a draw.

Yeah, and I think that it's just so empowering. I think the more people that realize diseases like type 2 diabetes or even Alzheimer's and dementia not only are reversible but, you know, preventable—

I mean, these are long-onset chronic diseases the mission really obviously needs to be prevention to start off with. Then when we are greeted with patients who already have existing disease, we know that there are interventions. I know you have spoke with Dr. Dale Bredesen, a close friend of mine, that the die is not cast, that there is some reversibility. That's breathtaking, especially when we realize that it's not monotherapy, it's not the use of a drug, it's a combined effort that can bring that about., but our mission needs to keep people healthy. My gosh. You know, you're talking about your program, your podcast, longevity, but it's not just, you know, the years of our life, but it's the life in our years. That's a quote from one of our distant presidents, President Abraham Lincoln, who really made it clear to us that it's our health span. And he didn't use that term, but you wanna live a long life, but you wanna be as healthy as you can and participate. And enjoy every year once you're getting older.

Why not?

Exactly.

I mean, my motivation is to be the 90-year-old grandmother out dancing like the Studio 54 grandmother, having lots of fun and jumping out of airplanes. So yes, I agree. It's about increasing healthspan for longer.

That's it. Well, I'm not sure so many of your audience members are going to know what Studio 54 was all about, but maybe you'll explain that at some point.

There's a movie as well.

There's a movie as well. Oh, okay. So they're going to get it. What a crazy time that was.

My parents used to go back in the day. Really? Yeah. They lived in New York.

Lucky I didn't go. I mean, I don't know how I would've ended up anyway.

The brain health might've been a bit different.

Probably would've been. Maybe better.

Who knows? Exactly. David, I've been a fan of your work for many years and I've read your New York Times bestselling books and following your blog. And before we jump into your new upcoming book drop, acid. I'd love to just discuss something I heard, a talk that you held in David Asprey's Virtual Biohacking Conference back in May on keys for better decision-making, becoming a conscious architect of your brain. I found this so compelling, and could you share with my audience your view on why so many people struggle with adherence and what actually goes on in the brain for that, for people looking to make these lifestyle changes?

It requires a little bit of a setup, and that setup involves understanding that, and this is a bit of a simplification for any of the neuroscientists out there. I understand you're going to think it's overly simplified, but let's just say that we have two major centers in the brain that are involved in decision-making. One more primitive area called the amygdala is the area that responds impulsively, immediately, in terms of what we decide to do. There's not a lot of thinking or cogitation that goes on. The amygdala wants to eat this food now. It wants to do whatever it wants to do now. And by and large, those decisions are self-serving. They deal with what I want for me right now, the rest of the world be damned. As contrasted to another area of the brain called the prefrontal cortex, which is behind your forehead. This is a newer addition to the brain. And we as humans, one-third of the brain's cortex is this prefrontal cortex. That's more than any other animal. This is a far more sophisticated area of the brain that does some important things. It brings in lots of other relevant information as it relates to our decision-making, and it really is the adult in the room. It exercises control over the amygdala, control over the more primitive area that says, I want to do it now. And it's basically, again, what we call top-down control or having the adult in the room that says, yes, I know you want to do this right now because it's what you want, but think of the consequences. Think of how eating this food is going to affect your blood sugar or deciding to go out drinking with your friends and driving home tonight might not be a great idea. So the problem is that there's a connection between this prefrontal cortex controlling then through top-down control, the more primitive area. That connection is incredibly important. When you reduce that connection, then the amygdala gets its way. Then we become more impulsive. We make decisions that are not thought out, that are what we want today, that have no concept of what it's going to be like for our future self, much less how it affects other people, how it affects the planet. Meaning that we lose the sense of empathy and compassion. And interestingly, that pathway, that connection between those two areas is threatened by something called inflammation, the underpinning of coronary artery disease, of type 2 diabetes, of Alzheimer's. We live in a world that's very inflammatory, that's increasing the amount of inflammation in our bodies. Everyone's heard in COVID this thing called the cytokine storm, where suddenly there's this incredible uptick of inflammation in the human body that goes around destroying things like the lungs and the brain and the heart. All kinds of things get damaged by these chemicals. But at the same time, as Dr. Bredesen has pointed out, we have what is called the cytokine, not storm, but the cytokine drizzle, meaning just a little uptick. In the amount of cytokines that are produced, but over a long period of time, that can similarly cause damage. Dr. Bredesen talks about the cytokine storm in the context of Alzheimer's, and what we talked about in our last book called Brainwash is how inflammation over time damages that connection, takes the adult out of the room, the connection between the prefrontal cortex and the amygdala so that our decision-making is hijacked and we are left to being guided by the desires of this 8-year-old that wants everything now, that wants everything for himself or herself, and loses the sense of connectedness to others, the sense of acting in a way that's beneficial not just to self but to others, which is so incredibly valuable especially today. And one last point on this topic. It's an interesting topic, and that is that one of the most powerful influences on the set point of inflammation in our bodies is obviously the food that we eat for many reasons. Pro-inflammatory foods in and of themselves, but also how food threatens the health of our gut bacteria. When we disturb our gut bacteria, we can cause a situation where the gut lining can be compromised. We get what's called a leaky gut, and that is a surefire way to increase inflammation in the human body. So our diets ultimately lead to, through these mechanisms, inflammation. The standard American diet, which has now become the Western diet, which has now become The global diet is a very pro-inflammatory diet. These, you know, highly modified processed foods that are global is very pro-inflammatory. So in a very real sense, these global changes in nutrition through increasing inflammation are changing how people globally are making decisions. It's locking people into self. And away from a sense of connectedness. And, you know, we see that playing out in terms of politics, in terms of decision-making, in terms of the overall rejection of the importance of making climate decisions, caring for the planet. So, wow, that big corporations have insinuated themselves into dietary changes that are affecting the planet and how that plays out in our decision-making. That's pretty much what I think I covered on that podcast that you referred to. It's something I think about quite a bit. And, you know, early on in our time together today, you asked sort of the question where you made a statement about why I do what I do. And over the years, it's becoming more and more clear that these ideas that we put forward as it relates to brain health have far bigger implications in terms of our decision-making and our behavior.

Thank you for summarizing that because I think that's worth just repeating. The food we're eating is actually impacting as far to say as the planet and politics and decision-making because it's moving much more towards self.

That's a heavy concept, isn't it?

That is a very heavy—

That's worthy of the show. Not that we're going to end right now, but we could leave the program with the viewers and let them think about that a little bit, how the global change in Food is affecting global decision-making.

Yowzers. Yeah. And what, in your view, would be the best, most easy-to-implement changes that we should all look to do in order to reverse that?

Well, the first thing I would say is to take a deep breath and recognize that we're all in this together. That's something people tend to say these days. Well, we're all in this together. We're here for you. But to mean it, to really mean it in not just your expression, but in your behavior, in your choices. Act in that way. And the more you act in that way, the more you reestablish that connection to your prefrontal cortex, despite the inflammation, despite, you know, the food choices, etc. And the other thing I would say is to recognize that we can control this. We can make better decisions. The problem is that we get into a tailspin that because our decision-making apparatus is hijacked, we make bad decisions that even further connect us to the amygdala and keep us away from the better decision-maker. So we have to consciously make some decisions right now to reestablish our connection to the adult in the room. That would be even for a couple of nights, do everything you can to get a better night's sleep, as an example. To maybe say today or tomorrow, I'm going to make it a point to spend 20 to 30 minutes each day outside in nature and leave my smartphone at home. Very, very important. That helps. That helps to light up that prefrontal cortex. You know, what else can you do? You can say, I'm gonna meditate for 20 minutes a day. Mm-hmm. And that will then help you regain the tools to make better food decisions. That's the biggie. That's probably the most difficult place to go because the primitive brain is screaming at you day in and day out to give it sweet because that's a survival mechanism that we've inherited from our ancestors. The ability that we have to seek sweet foods was a powerful survival mechanism. It told us that the food we are eating now, because it has sugar in it, was safe. And would help us survive during times of winter, caloric scarcity. The problem is that, you know, now we can get sweet every day, 365 days a year, and it's targeting survival mechanisms that now are inappropriate. So it is what we call this evolutionary environmental mismatch. These ideas were by— we would seek out the ripened fruit during our hunter-gatherer days or even before as primates. Would give us fructose, a fruit sugar. And fructose tells the body, get ready, winter is coming. And through the turning on of the production of a chemical called uric acid, then fructose signals the body to make fat, to increase its ability to store water, to increase its ability to make blood sugar to power the brain so we can be smart enough to avoid the two things that killed our ancestors. Starvation and predation. Starvation, we didn't have food. Predation, we got eaten by other animals. That's not a good thing. So powering the brain is critical for us because we have such a big brain. The problem is that now we're turning on that mechanism, that survival mechanism, day in and day out, and it thinks that we need to make fat and raise our blood sugar as a means of survival. And we see how it's playing out— diabetes, obesity, elevated blood pressure, you know, these metabolic issues as a consequence of triggering that mechanism and turning on in the body production of uric acid. And this is new information. In my day, uric acid was something that we measured in patients because as we knew, uric acid elevation related to the risk of getting something called gout, where you would have crystals form in your fingers and toes and it would hurt. And that was, you know, something that people who ate rich and sweet foods would get. So it was called the king of diseases and the disease of kings, because kings had the ability to eat all this rich food. We pretty much laid it to rest. We said, okay, high uric acid, you've got gout. If you have gout, you take this medicine, lowers your uric acid, home run. Well, now we know that uric acid has far more activity in your body than you ever knew, than I ever knew. And this research has been going on for the past 20 years showing that there's actually a paper that came out in 2016 from Japan that said uric acid in metabolic syndrome from innocent bystander to central player. So we knew that uric acid was elevated in diabetes and in obesity and high blood pressure, but we sort of said, well, that's cool. You know, it happens to be elevated. Interesting. But if you don't have gout, who cares? Now we know that it's actually involved in causing these problems through the very mechanism that we just talked about as a survival mechanism for our ancestors. So it's really quite an incredible story. And it's beyond that, an amazing tool, a new tool in our toolbox to help people regain metabolic health. And to be clear, it's these disturbances of metabolic health that open the door for virtually all the diseases you don't want to get, like heart disease and Alzheimer's and diabetes and obesity and cancer.

Would you say it's the leading contributor?

I think many things are at play here. Even something as simple as being sedentary, as, you know, sitting on your butt all day long, is a dramatic input to these diseases. But I think it's difficult to rank them. The reason that uric acid now is so high on the list is because it sets the stage for the elevated blood sugar and the elevated blood pressure and certainly the obesity and ultimately the insulin resistance and the diabetes that are powerful players. So it's really breathtaking. And, you know, Claudia, right now, you and I are talking about this, and so many people are unaware of it. That's great. You know, when I wrote Grain Brain, almost 10 years ago, originally people said, oh my gosh, carbs causing brain disease? You know, now of course everybody embraces it and they say, well, yeah, we get that high blood sugar clearly related to Alzheimer's risk. Being a type 2 diabetic is now associated with a fourfold increased risk of Alzheimer's. But early on, it took the mainstream a while to realize that, you know, Dr. Perlmutter isn't making this stuff up. In our new book, Drop Acid, there are over 400 references that make us realize that around the world, people have been looking at this for a couple of decades. And that in America and other Western cultures as well, there's the sense that we should just, again, live our lives however we want. Our lifestyle choices don't matter. And we're going to make a pill for you. And that's may I say it's ridiculous. It's beyond ridiculous though. It's hurtful because people deserve to know the truth that the biggest thing you can do to regain your healthy is to look at your lifestyle choices, not to hope for a magic pill. As it relates, for example, to diabetes, I was giving a lecture, I guess, 2 years ago, because it was pre-COVID, to several hundred mainstream doctors. I was there featured guest, why they chose me, I think, to maybe offer up a little view from the other side. And I asked the audience, again, mainstream doctors, what's the very best treatment that you have for diabetes? And everyone raised their hands. Oh, I use this drug. I use that drug. Wonderful. I said, oh, that's great. And another drug, whatever. And then I said, okay, what happens when you stop that drug? And they said, well, gosh, within a day or two, blood sugars are going to go up. Yeah, that's right, they will. And then I asked the audience, does that mean that you're actually really treating diabetes with that drug? If you're treating a problem, you're hoping that it's going to go away. Did any of the drugs that you offered actually treat the underlying condition? The answer was no, only treating the smoke and ignoring the fire. And I presented them with information from one of our colleagues, Dr. Sarah Hallberg, who has researched the effectiveness in terms of curing type 2 diabetes using this outlandish thing called a ketogenic diet. Who knew? And she has done this and taken people off of their medications, and their blood sugars remain normal, and their insulin resistance goes away. And yet you're not going to see ads on television, on the evening news, For that, you're only going to see people talking about how happy they are that they got their A1C below 7 because they're using a new drug. And it's, again, unfair. I think it's cruel. And, you know, that's the messaging at this stage of my life. I'm a little bit more vociferous in terms of getting out there and letting people know that there's another side to the story that they need to be aware of.

I completely agree. And I think it's just so important. I mean, specifically on type 2 diabetes. I know friends working in the pharmaceutical industry. I've seen the studies, I've seen the reports. You know, you take the medication, you're on the path to blindness, amputation, living in a wheelchair. It's really a horrible, horrendous disease. And Dr. Jason Fung, who I know you know as well, and others have the protocol. You do intermittent fasting and the ketogenic diet even just for a few months, and you can come off your type 2 diabetes medication and have a transformed life. You know, it's a few months in one direction versus a lifetime of suffering and pain in the other. So it just seems so logical. And that's why I think it's so important that people know that there is a choice and that there is an option, and that more education in the medical community needs to be done around this as well. So yeah, your work is so incredible. And just to pick up on your book, Drop Acid, first of all, I'd love to know where the name actually came from.

I have a copy right here. And what we're going to do is we're going to talk about this cherry in just a moment, because that's really extremely important. I came up with it. And I have to tell you that the people who have to do with what we named the book originally were not so keen. And I think what happened was I said, okay, I know you don't like the title because there's obviously, you know, a kind of a tongue-in-cheek thing going on here. And I said, take a deep breath, go with it for a couple of days. And you know what? Ask around and just let other people see how they feel about it. And people loved it. They got it. They understood the double entendre here. And so we went with it. So the acid that we're talking about dropping is uric acid. That's the home run message here. You know, plenty of other books written about dropping other kinds of acid, that's for sure. But we're not about that. It's about the incredibly focal role of uric acid elevation in causing us to have what's called metabolic mayhem. That's a term I like to use, but we are in Western cultures and really pretty much globally now going down the path of metabolic destruction. Here in America, we have 50% of adults will be obese by the year 2030. Now, you know, you hear all these predictions about this distant time, 2030, that's right around the corner. You and I are going to do it. We've already scheduled a podcast for 2030, probably. But, you know, the point is that's half of Americans, not just overweight, but obese. And, you know, even as it relates to children, right now in America, 10% of children between the ages of 12 and 18 have high blood pressure. Whoever heard of such nonsense? That's a metabolic problem and it's brand new. So, it's not a genetic issue. Suddenly, we've had this change in our genes. But it's a reflection of our genes being thrifty, putting fat away for the winter. That's what thriftiness is all about. But putting fat away for the winter is something that was a survival mechanism until really quite recently. You know, this all served us, this higher level of uric acid that we as humans have. Our uric acid level is 4 to 5 times higher than other mammals. Because other mammals have other mechanisms for getting food and surviving. But again, in the context of our history, it was wonderful. So again, this is this evolutionary environmental mismatch where our current lifestyle, our current environment is playing upon our genome and it's having a bad outcome. And my first writings on this topic were published a half a century ago. I wrote my first article on this topic when I was 16 in what was called the Miami Herald, still a newspaper, and talked about what about us living today who have this outdated machinery. In other words, we're not going to evolve quickly enough to get used to our current environment. So our genome isn't going to change. We have to act on the other side of the equation, that is work on the environment part, the foods we eat, the sleep we get, the nature exposure, how critically important that is. But we've now got this tool, understanding that one of the most powerful signals in our bodies that we have to think about is this elevation of uric acid. And it's been there. I would say many of your viewers might already have had their uric acid checked. It's part of the annual blood work that a lot of people get. But it was formally only in the context of gout. And I would say that if your viewers call their doctor, say, hey, by the way, what was my uric acid at my last exam? They say, well, it's in the normal range. Guess what? For me, that's not good enough. I don't wanna be in what somebody says is the normal range. I wanna be in the optimal range. And not the optimal range as it relates to gout, but the optimal range as it relates to reducing my risk for metabolic issues, and that is below 5.5 milligrams per deciliter. Now, the number that your doctor is likely going to tell you is, oh, you're below 7, you are fine. But what he or she didn't say is, as it relates to gout, what we wanna know is what's the best level for me and for you and everyone as it relates to being metabolically compromised. Having a lower uric acid level is what we want. Higher levels of uric acid— one really huge study that was published in 2016 looked at 90,000 people, 42,000 men and 48,000 women, and followed them over 8 years. And what they looked at was what is their risk of death? And they noted that the people who had the highest uric acid had about a 16% overall risk of death from any cause whatsoever. It's called all-cause mortality. But beyond that, they had a 38% increased risk of dying from a heart-related event and a 35% increased risk of dying of a stroke. Uh, even more interesting was the fact that for every point elevation above 7, every single point from 8 to 9, they had an 8 to 13% risk of dying from any cause whatsoever. And they concluded by saying that their feeling was that one quarter of type 2 diabetes is caused by this elevation of uric acid. That's a huge study, went on for 8 years. And that's compelling because who wants to die? Who wants to die of heart disease? Who wants to die of a stroke? You know, the term doctor doesn't mean healer, it means teacher. So that's what my mission is. So that's information that I'm trying to get out so people can understand there's a new sheriff in town. There's a new tool in your toolbox. Pay attention. This is important information.

It's really mind-boggling to know those numbers as well. And I wanted to just clarify on one point you mentioned that you said humans have a 4 to 5 fold ability to produce uric acid than other types of mammals. But I assume that that's variable in terms of what you eat and other lifestyle factors like resting, with sleep, etc. So if you have your uric acid levels tested, that's just a snapshot in time. But assuming you have bad lifestyle choices, it would be permanently elevated versus if you have good lifestyle choices and food choices, then it would be much lower. Is that a right interpretation?

Yes. What is good news is that our lifestyle choices can quickly lower uric acid. Are there genetics involved? There are. Absolutely, there are genetics involved. But every person on the planet has this genetic mutation that happened somewhere between 14 and 17 million years ago that took away the enzyme that breaks down uric acid. It's called uricase. So that happened in our primate ancestors during a time of cooling of the earth when food was less available. So those primates that lost the ability to break down uric acid, so it accumulated in their bodies, they survived and we inherited that part of the genome. So we all have that. But the good news is that lifestyle choices are profoundly effective in bringing that uric acid under control. I want to clarify one point. That study, if anyone's interested, that I just quoted with the 90,000 people, that was in the journal called Arthritis and Rheumatism. And it was in 2009, just if anyone's going to look that one up. But having said that, we have to ask ourselves, okay, where is this uric acid coming from? What is the signal for the body to make uric acid? And again, it's a survival mechanism that said to the body of our primate ancestors and to our Paleolithic ancestors, make fat because winter's coming. If you do, you might survive. And the mechanism then is that fructose, fruit sugar, was this powerful and remains obviously the most powerful signal to make uric acid. So our hunter-gatherer forebears, because they had a sweet tooth that you have and I have and everybody has, a survival mechanism. Who doesn't like sweet? If somebody tells me they just hate sweet, I haven't met that person yet, but if they do, I have to challenge them, but they may be right. You know, there's always Somebody, but anyway, this desire for sweet told our ancestors, number one, that this was a safe food to eat. There really aren't sweet foods that are toxic. Number two, that it was eating the fruit at the highest level of nutritional value. And number three, it activated these survival pathways so that we could survive. Fructose, fruit sugar, those blueberries that became ripe in the late fall, early winter, that We would eat in as much abundance as we could. The problem is today, from the 1920s until today, our fructose consumption has increased from 15 grams up to 55 grams a day. And going from 1970 to 1990, fructose consumption in humans has increased 1,000%. What is that fructose doing? It's telling your body prepare for winter. I think that's really as clean as I can get this. And the mechanism, the player here is uric acid. Uric acid receives this information, says, okay, everybody, we're going to put into play all of these survival mechanisms. Over there in the liver, we're going to turn on the production of glucose so we can power the brain. Also in the liver, we're going to turn on mechanisms to make fat. And we're also going to reduce our burning of fat. We're going to store fat so we can survive. We're going to actually increase inflammation so that we can be protected against various types of bacterial infections, for example. This shift in physiology is exactly what happens in animals that hibernate. For example, when bears are getting ready to hibernate, what do they do? They forage for fruit. They forage for berries. They pound their bodies with fructose, elevating their uric acid, turning on a mechanism that involves something called AMP deaminase, as opposed to something called AMP kinase. Maybe some of your viewers have heard of this AMPK. We activate AMPK with exercise, with caloric restriction, with drugs like metformin, quercetin as a nutritional supplement, berberine. That's the pathway that says don't store fat, burn fat. We don't make blood sugar. That's why targeting AMPK is done for diabetes medications. But in animals that are getting ready to hibernate, they don't want to mess with that. They want to go through a different pathway, which is called AMPD, so that they make fat, they store fat, their metabolism gets ratcheted down. And you can activate that pathway and make fat, store fat, reduce your metabolism, raise your blood pressure. Increase your body's production of glucose when you're eating a lot of fructose and turning on production of— who guessed it— uric acid. So that is why we want to drop acid, because dropping uric acid then takes this incredible new information and makes a tool out of it. It is a new lever that we can pull that gets to this fundamental cell signaling apparatus that tricks our bodies into finally realizing that winter's not going to come. We don't have to be storing fat to get through the next winter because, you know, this is a signal that we are tapping into every day of the year. You know, here in America, in our grocery stores where there are about 2 million, if you looked at the grocery stores around the country, different products, more than 60% of the packaged products in our grocery store have added sweetener. And by and large, that is fructose or high fructose corn syrup or some derivative. So it's not just, you know, things like soda and fruit juice. More than half of the foods that you go in the grocery store and are on the aisles are going to target this mechanism. So when we see, again, that a third of adults in America right now are obese, and that by 2030, as I mentioned, That's going to be half of Americans. Who's surprised by that?

Those are shocking statistics and of course very saddening. And I think, you know, a lot of people associate fruit with being healthy. And as you were saying as well, the high— and it is. Yeah. So I think it's— is all fructose made equal, first of all? And then obviously you have lactose and you have glucose and other forms of sugars, let's say. So are they all as evil, if you will, as the fructose?

Claudia, that's a great entrée. And I would say that to answer that last question with the different types of sugar, absolutely not. They are very different in terms of how the body perceives them. And, you know, sugar has been looked at simply because it's a source of empty calories, end of story. But the difference between glucose and fructose is night and day. Glucose is handled through a system that requires insulin. Fructose, not so. Insulin is not needed initially for fructose metabolism. Therefore, it was thought and really portrayed for many years to be the safer sugar, even for diabetics. Nothing could be further from the truth. Fructose immediately activates systems that cause insulin resistance, that make our body's ability to use insulin less effective. But you brought up the fruit question, which I have to admit is something every interview I have had lately has asked. It's a terrific question. It turns out that fruit is okay. It's the context. When you have fructose along with fiber, along with vitamin C, along with bioflavonoids, like you'll get from eating an apple or eating an orange, then this mechanism is not activated. That the bioflavonoids in having an apple and the fiber slows the fructose absorption, so you don't get this massive hit of fructose suddenly in your body. It sees that it needs to make uric acid because it has fiber, and the bioflavonoids actually work to transiently reduce uric acid production. And in addition, fruit has vitamin C, and vitamin C helps with the excretion, helps target our ability to rid our bodies of uric acid. So there's not an increase of uric acid in eating a reasonable amount of fruit. You know, it's said that an apple a day keeps the doctor away. Well, that doesn't mean, you know, 3 bowls of blueberries, some pineapple, and who knows what else. You're going to override the system. But because I said that, that doesn't open the door then for fruit juice. Fruit juice is a powerful and sudden surge of fructose in your body. And your body says, whoa, it looks like this person just saw the weather report and the cold weather's coming and all the food's going to go away. We better get ready and make some body fat so that we don't starve and that we don't become dehydrated. Body fat is a powerful hedge against dehydration. When we metabolize the fat in our bodies, we create two things: carbon dioxide, which we exhale, and water. So storing fat is a powerful survival mechanism for survival in times of water scarcity. You know, the camel that walks across the desert and has no water and yet seems to survive has this massive hump, may weigh as much as 80 pounds. It's not filled with water. You know, you think, well, there's a big container of water in there and you could tap into it. It's all fat. And slowly, as that camel walks across the desert, that hump gets smaller and smaller because it's utilizing that fat. It's metabolizing that fat, yes, for energy, but also in the production of water. Why do you think whales have so much body fat? Insulation, I get that. Cold water. But also a source of calories, of course. But where else are they going to get fresh water? There's no spring that they're going to drink from. They're in the ocean. They don't drink seawater and somehow desalinize it. They make their own fresh water from their body fat. So in that context, making body fat for you and me could be a survival mechanism if we had no access to fresh water anymore. Well, we do, so we don't need to pack away the pounds for calories, for insulation, and for water.

So interesting. For every pound of fat What percentage would you say is water?

Well, it isn't water, but it's metabolized into water, and it's over 1.1 grams of water made for every gram of fat that is metabolized. Now, we can make water when we metabolize carbohydrate as well, and that's a lot lower. It's about half as much, a little less than half as much. So fat becomes not only a very dense source of calories, 9 calories per gram, but it's also a wonderful storage mechanism for water that we can then use. I mean, you know, one of the fattest animals on the planet is the hummingbird. Who knew? Hummingbird, why is that? The hummingbird is drinking nectar. What is nectar? It's high in fructose. You want to have hummingbirds in backyard, you take a container, you fill it with sugar water, and they'll come. Right? They know. And when they drink it, they make fat. And this fat then serves them as a source of water and calories so they can migrate thousands of miles without having to refuel. Who knew?

Who knew?

You know, to be sure, they've got a very, very high metabolic rate, you know, with those wings flapping the way they do.

And so they're able to burn it off as well. And I think just to be clear, we're talking about, you know, fat and water, but obviously there's a lot of diseases related to high levels of fat and obesity. And maybe just for listeners that are not so familiar with, you know, metabolic health and what's happening around metabolic health, can you talk a little bit about what exactly metabolic health is and the health risks that come from not taking care of it properly?

Let's deconstruct a term called metabolic syndrome. And there are 5 components of metabolic syndrome. They include insulin resistance, which raises blood sugar. A big belly, if you will, you know, a high what's called body mass index, elevation of blood pressure, elevation of something called triglycerides, and then something that's called dyslipidemia, meaning troubles with good and bad cholesterol. And in America, 50% of people age 60 or over have 3 of the components or more of metabolic syndrome. You have to have 3 of those 5 to be characterized as suffering from metabolic syndrome. And 88% of all American adults have at least one component, meaning that only 1 in 8 American adults is metabolically in good shape. That's scary business because, you know, these are issues in and of themselves, but it's most important to recognize that these issues underpin our most pervasive health-related issues. The causes of death, the number one causes of death on our planet have at their genesis metabolic dysfunction, metabolic issues, whether it's hypertension or elevated blood sugar or the obesity, whatever it may be. The number one cause of death, even during the time of COVID still the number one cause of death on planet Earth are the chronic degenerative conditions. Like coronary artery disease in our country, uh, still ranked as number one, these cardiovascular events, Alzheimer's, many forms of cancer, and certainly type 2 diabetes. These are metabolic issues at their core. Bad news. Well, good news. Bad news that this is going on. It's good news now that each and every one of your viewers gets this and gets the notion that metabolic diseases are under our control. We can make choices to rein in our metabolic mayhem, regain metabolic health, and therefore really put an end, or at least dramatically lower our risk for the number one causes of death on planet Earth. This is the empowering part of our time together today, Claudia, that is that the tools are there. They've been there for a long time. You know, researchers have been looking at what we can do to improve our metabolic health. Know your blood sugar. In an ideal world, you could know your blood sugar day in and day out by wearing what's called a continuous glucose monitor. Know your uric acid level. You can go to the doctor and have it checked, or you can buy a home monitor online and know your uric acid level right now and in an hour if you want to. Get your body weight under control. Here are the tools to make that happen. Most importantly, I think fundamentally is to recognize that we are experiencing the manifestation of targeting our DNA, targeting our genetic legacy with information that it can't use, that it is corrupting, that our gene expression is being changed by our modern world, by the food choices we are making, the lack of sleep, lack of exercise. Believe it or not, these are changing our gene expression. I mean, when I was in medical school, we were told our DNA was in a glass case. That was it, end of story. It's the indelible code that determines everything about you, your future, your health. Everything's genetic. Now we know that every bite of food that we take, every threatening phone call that we get, every time we decide to stay up a little bit later than we should, Or every time we exercise, get out in nature, meditate, fast, involve time-restricted eating, eat good food. Either way, we're changing our gene expression. We are the architects of the expression of our genetic code. That's a very heady obligation, isn't it? Because it gives us a lot of responsibility now. To do things right. But once you get your arms around that, it's exceedingly empowering to know that, you know, I might have been going down the wrong road and not so happy with my weight or my inflammation markers, my blood sugar, whatever it may be. But my DNA is sitting there waiting for me to make changes so it can turn on the good genes and allow me to regain my health. 90% of of the DNA parts, the DNA that codes for health and longevity are under our control, are sensitive to, I'll use a technical term, epigenetic influence, meaning above our genome, above our DNA. And those epigenetic changes are influenced by our lifestyle choices. We control, by and large, our gene expression, and can determine our health destiny. And now we know that a powerful lever, as I mentioned earlier, is this uric acid. You know, once we rein in uric acid, and it's not the end-all, that's for sure, but it's certainly part of our toolbox now.

Fascinating and so empowering as well. And I hope all listeners, you know, listening to this really feel empowered that they can really take their health back into their own hands. And David, I'd like to ask ask you, what would you say are the key strategies to lowering the uric acid? You mentioned obviously sleep and meditation. You know, is there a certain protocol that you recommend? And before, you were showing the book with the cherry on it. Can you maybe talk about that as well in terms of certain foods?

I didn't design that cherry. That came from our team. And I think if you look at it closely, what's really cool about it— can you notice that it's falling?

Oh, yes. Yeah.

Uh-huh. So the implication then is cherry bringing down uric acid, and it does. So there are a lot of studies that show how tart cherries, more so in women than men, have been used as gout treatment for a long, long time and will lower uric acid. But let's look at the big players here. And first and foremost, we have to double-click on food because that's where we get into trouble. And in that realm, the biggest player these days is, of course, fructose. Fructose is immediately, through multiple steps, metabolized to form uric acid. So we want to read labels. We want to recognize fructose by its multitude of different confusing names. We list them in the book. Want to read labels for any kind of added sweetener and recognize that it's everywhere and it's insinuating itself into our lives, and it's done so, so that we will cater to our primitive brain because we want sweet. We have to override that. We have to bring the adult back in the room and say, not so fast. So fructose is by and large the biggest issue today, but uric acid is also made from two other things. Alcohol is also immediately metabolized into uric acid through multiple steps, but as we look at alcohol, it's not all alcohol that is a risk here. That wine, at least in women, tends to lower uric acid, or is associated, I would say, in food frequency questionnaire-based studies with lower uric acid.

All types of wine, just to ask on that, because I think it's—

it looks like— well, my recommendation would be red over white. Red better than white.

And a dry red, or any one?

Well, I would think drier would obviously be better, but I can't back that up with any research. But I would say drier as a wine wine recommendation is obviously seems to make the most sense. Hard liquor raises uric acid, but the biggest player of all is beer. Beer, yes, contains alcohol, but it also contains something called purines. Purines are the breakdown products of DNA and RNA. The reason beer is so rich in purines is because it's made with yeast, brewer's yeast, and it turns out that these purines also form uric acid, which is why we want to avoid the third class. And that is animal products that are very high in purines. That includes organ meats, things like liver and kidney, and certainly some small fish like sardines and anchovies. You can have them, but you're going to want to follow your uric acid and see if they are, you know, causing you to have trouble dropping your uric acid or may even raise uric acid. Not likely, but it rounds out the list. Then let me mention just a couple of other supplemental ideas. We know that both quercetin— and my recommendation would be 500 milligrams per day— and luteolin, 100 milligrams per day, both target an enzyme that makes uric acid called xanthine oxidase. So if we add those to the program, very powerful. DHA, which is an omega-3, tends to offset some of the damaging effects of fructose. So that's on the list, about 1,000 milligrams a day. And then I like chlorella because chlorella vulgaris, you can buy at the health food store, 1,000 milligrams per day, has been demonstrated to have some really nice effects in terms of what's called non-alcoholic fatty liver disease. That's what happens to your liver with fructose consumption. And ultimately leads to problems in terms of how the liver works. The last thing I'd recommend is good old vitamin C, 500 milligrams per day. That way you get another benefit of the fruit without eating a lot of it. But vitamin C, as I mentioned earlier, helps our bodies reduce or eliminate uric acid, so therefore the level will be lower. I think really importantly, people should get to know their uric acid levels. Get a home uric acid monitor. I use a device called U-Assure, U-A-S-U-R-E. Super simple, just like in the old days I used to prick my finger and check my blood sugar. I don't do that anymore because I wear a continuous glucose monitor that's telling me day in and day out what my blood sugar is. But I think in the years to come, we're going to see that same kind of technology available for us for uric acid and, and other metrics for sure. So the main thing is to get on board with understanding how valuable this is, getting your levels checked, and then making changes to bring it down below the magic number. For all of us, it's 5.5 milligrams per deciliter. Now, I know that your podcast is viewed internationally, and across the world there are other units of uric acid that are used, but I would say that if you can get that, whatever the units are, converted into milligrams per deciliter, there's a simple equation for each conversion. That's the number that you can then use that will allow you to understand where you are and if you have work to do. The average uric acid level is 6 in America in adults now, which is high. Around 1920, the average level was 3.5. So it's not as if that level is genetically determined. It wouldn't have gone up. It wouldn't have changed one way or the other. What's changed is the inputs, food, sugar, fructose. So these are powerful tools.

This is so good to know. And just for listeners around the world, one conversion tool that I use, I find very easy is you can literally put into Google whatever your metric is and then ask, what is 5.5 milligrams per deciliter in whatever conversion you need. So you can ask Google and Google will actually give you the answer if you want a very quick and easy way to convert.

So good old Dr. Google, it's great.

Yeah, my friend Google knows everything. I have a few follow-on questions. One is around the testing for uric acids and the difference between uric acid and urea. Urea comes on every blood panel test results, but uric acid doesn't. What is the difference for people trying to understand?

Completely different. You know, certainly kidney function will affect both of those metrics, but urea, which is usually measured in a lab test called BUN or blood urea nitrogen, is a breakdown product of metabolism similarly. But is more of a direct measurement of kidney functionality along with another measurement called creatinine. So while they sound kind of similar because they both start with U-R, they are completely different. So don't get confused if somebody has been told that their urea level is elevated. Well, that needs attention, but that's a more of a marker of kidney abnormality directly than would be, for example, uric acid.

And on a typical blood panel, uric acid would be tested. You just need to ask your doctor.

Any comprehensive blood panel— I mean, if you go in for a blood count, that's going to look at how many red blood cells you have, what is your hemoglobin, your hematocrit. If you go for a small metabolic panel, that might look at your blood lipids and your glucose. But usually in these comprehensive panels that have 18 to 20 different metrics, you'll find uric acid. But again, when you get it and you ask your doctor, hey, what does this mean? Generally, you're going to be told that it means you either are or are not at risk for getting this disease called gout. True. That's true. But there's a lot more information now. And if you mention metabolic issues to a doctor, likely, you know, he or she may indicate, well, I don't know anything about that, and therefore I don't subscribe to that. Well, it is often said that people tend to be down on what they are not up on. And, you know, in that situation, I would simply have— and I've recommended people ask your doctor to do the following— Google, bring in our friend Dr. Google, and Google just two terms: uric, U-R-I-C, you don't even have to put in uric acid, and the word metabolic. And then he or she will get an incredible download of all the articles that talk about, you know, I've quoted some of them today, talk about the role of uric acid in metabolic issues. Don't put in uric metabolism because metabolism is then going to simply focus on how uric acid is metabolized. We want to put in uric and metabolic. That will relate uric acid to metabolic issues like diabetes, weight gain, hypertension, dyslipidemia across the panorama, and even kidney disease and what is called non-alcoholic fatty liver disease, which I mentioned briefly earlier.

Your book also features a groundbreaking LUV, L-U-V, or lower uric acid values diet. Can you talk a bit about what you share in your book?

We wanted to include the how to eat and really to answer the question of, oh my gosh, my life is going to be so restricted, I'm not going to have food to eat. And really, nothing could be further from the truth. We want to create recipes and have a diet plan, which is what we did, that reduces and virtually eliminates, as best we can, fructose. So it's a very low fructose supplying diet, but it's also one that's low in sodium because, interestingly, Elevated sodium in the human body converts or leads to the activation of a pathway that converts glucose, your glucose floating around in your bloodstream, into, you guessed it, fructose. So while you've cut your consumption of fructose, you can actually be making fructose in your body, and you don't want to do that. And that happens when your body thinks it's dehydrated by virtue of the fact that the sodium level goes up. Now sodium can go up when you're dehydrated, that's a powerful signal, but also sodium goes up if you're eating a lot of sodium, a lot of salt. So we want to be salt restrictive as well. But then many of these foods have our hero ingredients, things that I've talked about— high in the bioflavonoids that can reduce uric acid production, high in vitamin C that can help with uric acid excretion, high in dietary fiber that can reduce the speed at which fructose is brought into the intestine. So they're all designed with hero ingredients that are good for this whole paradigm of fructose and uric acid, but also hero ingredients that are really good for our metabolism as well, like the cruciferous vegetables, like having again lots of dietary fiber, things for example like broccoli seeds and broccoli sprouts, which we can turn into incredibly powerful chemicals like sulforaphane that help reduce inflammation, that help the body turn on its antioxidant system, that help with detoxification, for example. So a lot of hero ingredients, and they are incredibly wonderful recipes that are delicious. I'm not such a great cook, but my wife is a wonderful cook, and these recipes are created by a dietitian involved in looking at creating recipes based upon certain parameters, which we provided. And so they are over the top.

Excellent. And the book is not yet launched. When is it going to be launched and where can people get access to Drop Acid?

So Drop Acid is available everywhere. Amazon globally, bookstores globally. Already being translated into 5 languages. I think Portuguese, Chinese, Italian, and Russian, and of course, English, both in England and America. And I would expect more of that moving forward. It'll be distributed on February 15th, 2022, but it's already the number 1 new book in brain health by virtue of the fact that people are pre-ordering it. And I'm happy that people are pre-ordering because, you know, there are things called supply chain issues that we are all laboring through. So, you know, I guess the people on the top of that list will get there sooner than later.

Yeah. So a big call out to everyone to pre-order while supply is— so already a bestseller. So very, very exciting to see. David, what trends and developments in the longevity space do you find most exciting?

Well, there are a lot of technical trends. That are great, like the wearables. And I think that's going to be a major help. I think the biggest exciting trend or development for me would be the work of a Dr. David Sinclair at Harvard, where he's looking at genetic reprogramming, the ability of actually changing gene expression, reverting cells that are damaged back to an earlier stage in their life. I mean, it's really breathtaking. But I think the biggest issue will be for us, used by most people, will be what is called infomatics, where we're able to use information and make lifestyle changes. So I'd indicate people should certainly keep their eye on that development. A wonderful book by Dr. Eric Topol about this whole notion about what the future is going to look like using technology like AI and wearables, et cetera.

It's really exciting. And also the continuous glucose monitor has been eye-opening. I know you're advising to—

In fact, we actually have a chapter in Drop Acid dedicated to that technology in particular, CGM.

I'm a huge fan. Yeah, it's so insightful because you really can see very, very personalized what the food you're eating, what stress levels, exercise, how it affects your blood sugar and what's really going on in your body chemistry by just scanning your smartphone. So yeah, I use it as well. Where can people learn more about what you're up to, be it social media or your—

I would say the best Clearinghouse is drperlmutter.com. Drperlmutter.com. That'll lead you to my blogs, Facebook, my interviews on The Empowering Neurologist, which is a YouTube channel, and there's plenty of information there.

Wonderful. And do you have any final ask or recommendation or parting thoughts or message for my audience?

I think the message is to be your own health advocate. That, yeah, doctors have great information for you, but we recognize that they're as limited as any other person can be, that, you know, we really have to take the bull by the horns and be our own health advocate and make changes that can pave the way for a better health destiny. And we have the tools for that now.

Really exciting. Thank you so much, David, for coming on today. It's been such a—

It's very nice to meet you and thank you for this very kind interview.

Hey everyone, it's Claudia von Boeselager here. Before you take off, I hope you enjoyed the episode and learned as much as I did. If so, please hit subscribe so you don't miss out on our next episodes. I would also love to hear what you thought, be it your favorite part, quote, or other feedback from the episode. So please leave a written review on Apple Podcasts or on social media. And if you think this episode will help someone in your own life, share it with them. Together we can change our own lives and the lives around us for the better. Until next week, goodbye, farewell, and choose to live well.