Dhru Purohit Show - Could Uric Acid Be The Key to Losing Weight, Controlling Blood Sugar, and Achieving Extraordinary Health? with Dr. David Perlmutter

Episode Date: February 10, 2022

This episode is brought to you by ButcherBox and InsideTracker. Researchers around the globe over the past decade have revealed that uric acid, previously thought of only in terms of gout, actually plays a central role in metabolic disorders. So, how is uric acid orchestrating this metabolic mayhem? This week on The Dhru Purohit Podcast, Dhru sat down with Dr. David Perlmutter to talk about how uric acid plays a major role in fat storage, insulin resistance, and other metabolic and chronic degenerative diseases that are driving illness and death in our country.  Dr. David Perlmutter is a board-certified neurologist and five-time New York Times bestselling author. He serves on the board of directors and is a Fellow of the American College of Nutrition. He is the author of Grain Brain, among other works, and his upcoming book, Drop Acid, comes out February 15, 2022.    In this episode, we dive into:    -Surprising foods that drive uric acid levels (7:23) -How elevated uric acid levels directly lead to increased fat storage (9:16) -The consequences of elevated uric acid (15:38) -The main culprits that lead to elevated uric acid levels (17:42) -How to test uric acid levels and what the optimal range is (29:49) -The relationship between elevated uric acid and the risk of heart disease and Alzheimer’s (35:38) -The biggest drivers of fructose in our diet (46:43)  -The connection between foods rich in purines and uric acid (1:09:15)  -Why you should avoid agave at all costs (1:25:34) -Quercetin and how it helps lower uric acid levels (1:31:11)  Also mentioned in this episode -UASure Uric Acid Meter - https://www.uasure.com/ For more on Dr. David Perlmutter, follow him on Instagram @davidperlmutter, Facebook @davidperlmuttermd, Twitter @davidperlmutter, YouTube @davidperlmuttermd, and through his website https://www.drperlmutter.com/. Get his book Drop Acid at https://www.drperlmutter.com/books/drop-acid/. This episode is brought to you by ButcherBox and InsideTracker. For a limited time, new subscribers to ButcherBox will receive ground beef FOR LIFE. When you sign up today, ButcherBox will send you 2 lbs of 100% grass-fed, grass-finished beef free in every box for the life of your subscription. To receive this offer, go to ButcherBox.com/dhru. InsideTracker provides detailed nutrition and lifestyle guidance based on your individual needs. Right now, they’re offering our podcast community 25% off. Just go to insidetracker.com/DHRU to get your discount and try it out for yourself. Hosted on Acast. See acast.com/privacy for more information. Learn more about your ad choices. Visit megaphone.fm/adchoices

We know that fructose drives metabolic dysfunction and that metabolic dysfunction is at the core of our most dreaded common diseases of our time. Hi everyone, Drew Prode here. Today we have Dr. David Prohmutter back on the podcast to talk about a simple biomarker that can radically transform how you look at your health. Stay tuned. Hi, everyone, Drew here. If you're a fan of the show, I'd love your help.

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Just go to inside tracker.com slash Drew. That's D-H-R-U to get your discount code and try it out for yourself. That's inside tracker. I-N-S-I-D-E. Tracker. T-R-A-C-E-R-D-R-D-R-R-D-R-R-U for your 25% off. Welcome to the Drew Perot podcast. Each week we explore the inner workings of the brain and the body with one of the brightest minds in wellness, medicine, and mindset.

This week's guest is Dr. David Perlmutter. Dr. David Perlmutter is a board-certified neurologist and a five-time New York Times best-selling author. He serves on the board of directors and is a fellow of the American College of Nutrition. He's the author of many well-known books, including Grain Brain, And he has a new book out, which we're talking about on today's podcast called Drop Acid. Drop Acid is a deep dive on the surprising new science around Uric Acid and how it's central when it comes to our ability to lose weight, control blood sugar, and achieve extraordinary health. Dr. David Perlmutter, welcome back onto the podcast. It's a pleasure, as always, to chat with you.

It's great to be back and it's great to be traveling again. Before we go into the background story, which by the way, just to refresh your memory a little bit, you came on the podcast last time and you dropped a little hint about this book. A uric acid bomb. Exactly. You dropped a little uric acid bomb. You completely blew my mind. I went down this whole rabbit hole of researching after, and we're going to be talking about all those things today. But before we jump into the background story of the book and everything, I want to start off with some immediate value that we can give to our audience that's there.

Tell us about a few surprising foods that came across your plate, foods that like even maybe one or two, that you looked at through a completely different lens after doing the research and the deep dive that you did around this book and then we'll unpack the whole concept of uric acid, what it is, why it matters, and how you figured it out. Okay, here are the bullet points. Yeah. beer, sardines, anchovies, and of course, fructose, the sugar fructose uniquely. So all three of those categories as being foods, because I said surprising, I didn't say whether they were good or bad, quote unquote. And you would say that these are foods that all drive your ac acid levels. And that's why if you're eating them or you're consuming any of these foods on a regular

basis as part of your diet, you really want to be paying attention to this interview. That's right. And, you know, for years, there's been this attempt to make us believe that fructose was somehow a safer, better sugar because it doesn't elicit an insulin response. And therefore, hey, it's a great sugar for everybody and diabetics especially. And the truth of matters, nothing could be further from the truth. We know that fructose drives metabolic dysfunction and that metabolic dysfunction is at the core of our most dreaded common diseases of our time, the coronary artery disease, Alzheimer's, cancer, diabetes. So it is, you know, understanding this new biochemistry of the downstream metabolites of fructose and specifically uric acid that is a revelation and it is exceedingly empowering for each and every one of us. This is a new tool in our toolbox like we've never had before and I just get pumped up to talk about it. So take us on the uric acid journey.

Most people aren't always familiar. They know that sometimes they see it on a test report back from their doctor. There's not much discussion around it. How does the traditional world of medicine look at uric acid? How do you look at it now through the lens of some of the surprising research that's been actually out there for a few years now that you came across? And what does it mean to us as we're thinking about how to optimize our health? I'd say that you probably wouldn't need to ask me in a

question for the rest of our time together today. Really? Because that is, it's why we're here, because we all grew up in the medical field looking at uric acid through the lens of gout and perhaps kidney stones. End of story. And if you went to your doctor and had your blood values done, typically it would contain anywhere between 12 and 20 different parameters. In general, uric acid would be included through the lens or in the context of gout risk or or having kidney stone risk. And now we recognize that uric acid is far from this inert metabolite that might be related to gout, that it is a central player.

It's gone from, there's a title actually of a journal article, Euric acid in metabolic syndrome from innocent bystander to central player. So we recognize that it is exceedingly active in playing a role for the host of metabolic issues that threaten our health, whether it's high blood pressure, fat deposition, keeping fat locked up, gluconeogenesis or the creation of blood sugar in your body, insulin resistance, oxidative stress, inflammation, nitric oxide inhibition, all of these mechanisms are now associated with uric acid and were all good things in the day. That becoming insulin resistant, which we now, every every guest on your show who talks about metabolic health, say, we had to do everything we can to

not become insulin resistant. I mean, Dr. Hyman's written books on this topic, Dr. Lustig as well, many people, myself included. And yeah, it's true that these days we should do everything we can not to be insulin resistant, but for 99.99% of our time on this planet, being insulin resistant, having blood sugar higher than what we consider normal was a very powerful survival tactic. We wouldn't be here today if it weren't for the fact that we humans, by virtue of our thrifty genome, have a real strong predisposition to raise our blood sugars, to make body fat, to increase our blood sugar, to make more blood sugar in our bodies to power the brain, so that we can avoid the two things that threatened our answer. ancestors, starvation and predation.

You know, we've always been at risk of not having food and we've always been at risk for being eaten by something else in the forest, right? Those aren't really risk that we encounter these days. We're not, you know, we're not at risk for having another animal come along and eat us anymore. So I think that where we'll take our discussion today is to an incredibly fascinating place that through the years of our evolution, we have. had some unique changes in our genome that paved the way for us to be very thrifty as it relates

to the calories that we've consumed, that we've always banked calories in the form of fat so that we would have a hedge against starvation. And that's where this elevation of uric acid comes into play. So what we've learned is that between 14 and 17 million years ago, there was a series of mutations in the genes that made an enzyme called uricase that breaks down uric acid. And these genetic mutations turned off the production of this enzyme. So our uric acid levels increased. And now we know what that means. It means that higher levels of uric acid told our bodies that winter was coming,

told our bodies make fat, store fat, make more blood sugar, raise the blood pressure. Because that's how we would survive when we didn't have food. and we didn't have water. So those of our ancestors that had these mutations then would survive when food was scarce and they pass those genes onto you and to me and to every human walking the planet now, a time when we don't necessarily have food scarcity. And the biggest trigger of all, to lead back to your original question, is the sugar fructose. Fructose becomes available to us in the late summer and in the early fall. Well, when I say us, I mean, perhaps our hunter-gatherer forebears and our primate ancestors,

we consume fructose. It's metabolized into uric acid, and uric acid tells the body, hey, get ready. Winter's coming. Make fat. Get ready. Get ready almost for hibernation. That's what animals that hibernate do. They have higher levels briefly of uric acid.

They make more body fat. Then they hibernate, and they have the calories to, sustain themselves. So it's an incredibly interesting story because ultimately where we go with that is to where we are today, where we experience the consequences of this evolutionary environmental mismatch. So we have this genome, this physiology, this human body that wants to save every calorie, that wants to make fat to hedge against times of caloric scarcity. And yet, We're triggering that mechanism to make more fat day in and day out, you know, to the extent that a third of American adults is obese.

And that number is going to be 50% by the year 2020. Not 2030. We think 2030, you know, that's in the distant future. I know this is probably evergreen, but I'm going to say, as we have this conversation, it's eight years from now, 50% of American adults will be classified as not just being overweight but obese. You know, you mentioned consequences. Obesity is one of them and uric acid plays a central role in that. We'll come back to that. What are some of the other consequences, diseases that people might think of that are out there, that they know that people, maybe even

loved ones, maybe even themselves that they're diagnosed with that have a direct connection all the way back to the upstream elevated levels of uric acid that people are facing. So the number one cause of death on planet Earth are the chronic degenerative condition. And those include things like type 2 diabetes, coronary artery disease, Alzheimer's type cancer, various forms of cancer. So what's killing people across our planet are these chronic degenerative, inflammatory, metabolic diseases? At their core, there is metabolic dysfunction that paves the way.

Metabolic dysfunction so that we gain weight. Our blood sugars go up. We become insulin resistant. We have higher levels of inflammation. in our bodies, a central mechanism for things like Alzheimer's and coronary artery disease. So those are the big threats. Even bad outcome as it relates to COVID infection is seen in people with higher levels of uric acid. So it is front and center leading to this metabolic dysfunction in the day of our caloric

consequence, in the days when we didn't know we would have calories or not, we knew or we didn't. These issues would be life-saving. They paved the way for our survival in the context of possibly starving to death. That's not generally where we are today. So people should then understand that we're set up to gain weight. We're set up to make more blood sugar by virtue of this innate mechanism that all humans possess. And that is how we trigger uric acid production that is the danger signal. It tells the body, get ready. And then we should then ask ourselves, well, what are those inroads to elevating uric acid? And its diet, its lifestyle diet primarily these days, fructose. Our fructose consumption has dramatically increased over the past century,

whereas in the 1920s, we would consume perhaps 15 grams of fructose a day. Now that number's up to 55 grams, that, you know, we're consuming 17 teaspoons of sugar a day, the average American, and that's table sugar, sucrose, which is 50% fructose. And fructose and glucose are totally different molecules, though their chemical formula is the same, their configuration is totally different, and their metabolism is like night and day. We metabolize glucose by using a hormone called insulin, drives glucose into the cells, creates glycogen, we store it. Fructose has nothing to do with that.

Fructose is metabolized into something called uric acid, and the consequences of that are manifold. They are severe, and they represent a central player in our time of metabolic discontent, if you will. When you look around the planet, you know, to get back to your question, these metabolic issues are the number one causes of death. And they are avoidable. And, you know, as I was getting ready for our interviews today, I was thinking about some of the questions you might ask. And I realize that we say in general that Alzheimer's is not really a genetic disease. You know, about 4 to 5 percent of Alzheimer's patients have a real strong genetic issue. puts them at great risk. We don't say, for example, coronary artery disease or type 2 diabetes

are really genetic issues. But through the lens of this genetic change that happened to our ancestors and the mismatch then between what our ancestors and even our hunter-gatherer forebears experienced and the world of today, we still have those genes. So in a very real sense, Alzheimer's and type 2 diabetes and coronary artery disease because they are metabolic are 100% genetic. They are the downstream manifestation of this mismatch between our physiology dictated by our genome and how we speak to our physiology based upon our lifestyle choices, primarily the food we eat, but also the sleep that we get or don't get, the exercise, the stress, the other lifestyle factors that are truly influential in relating to what our genome expects.

Yeah, it's so profound when you zoom out and you think about it. It's like this mutation, as you've been talking about, this genetic mutation that we had, and the people that didn't have it, they didn't make it. So we're all ancestors from those people. And from my understanding, because 15 million years ago, it was about it was apes. It was before Homo sapiens, right? Long before, yes. Long before Homo sapiens.

And so these ape ancestors, there was a group of people, group of apes. ancestors that didn't have this mutation they couldn't survive winter there wasn't enough fruit trees that they had access to they couldn't store fat they couldn't do our evolved ape ancestor version of making it through the winter instead of like a full-bone hibernation right because at that point in time there wasn't really a full-blown hibernation period that that our ape ancestors were going through and now because our modern lifestyle has changed so much around us and there's so much fructose in our environment. We'll talk about the top sources

that are out there. Surprisingly, some foods that many people think are healthy that they're eating on a regular basis that could be driving these high uric acid levels. But because we're so much surrounded by it, we've changed and our environment has changed, but our genes have not changed. And that's why we're in this mess that we're in today when it comes to chronic disease. That's right. And, you know, so it's an environmental pressure. Evolution is the response to environmental pressures of one sort or another. And our genome basically is selected for those mutations that will then confer certain superpowers, if you will. And, you know, this specific

Eury case set of mutations took place over a couple of million years. So it didn't happen very quickly. And in fact, the changes during the middle Miocene period were actually very slow with the earth cooling and the progressive loss of food availability. Now, we've turned the tables on these genetic mutations in a century or two, and we cannot adapt. And I actually wrote my first article on this topic half a century ago when I was 16. I published an article in the Miami Herald talking about, you know, what's happening to us who are, in my words, stuck with this outdated machinery. So we can't evolve quickly enough to be able to be in concert with our current environment. We can't change our genome. We don't have that technology just yet. Maybe we will. But we can sure

change our environment. This is sort of the underpinning of the so-called paleo movement to try to emulate the environment of our ancestors that coexisted quite well when you looked at the relationship between genome and environment. Now there's a great disparity between those two. We want to try to do what we can to give back to our genome those signals so that it can keep us alive, those salubrious signals that we give via our foods, the environmental choices that we make. And that's what this is all about.

And focusing in on uric acid as being that sentinel, that alarm signal, and we want to do everything we can not to trigger it. You know, there's a really powerful study from 2016 that looked at 42,000 men and 48,000 women, a big study. And they showed that those in the group, they followed these people over eight years. Those in the group who had the highest level of uric acid had about a 16% increased risk of what is called all-cause mortality. What does that mean? Dying from absolutely anything. From being hit by a bus to coronary R disease, having a stroke, you name it. But more specifically, those, their risk for cardiovascular death in the group with the highest uric acid was increased by 39 percent, almost 40 percent. Risk of dying of a stroke increased by 35 percent. And for every

point of elevation of the uric acid above seven, the units we use here are milligrams for decilator for every point. So at eight and then at nine, there's an additional eight to 13 percent increased risk of death from any cause whatsoever. The final conclusion of that study was that in this group of 90,000 adults, that a quarter of the diabetes, type two diabetes had its origin in elevated uric acid. So we have to take this really seriously. But it's good news. Take us a little bit on the background journey and you write about it in the book about how you went down the rabbit hole of uric acid.

And there's a researcher that'll let you get a chance to talk about. But, you know, you were out there running one day listening to a podcast. And as you tell about how you came across this work, which led you to writing this book and a new friendship that was in your life with this researcher, also help us understand how his work, what gaps in your, what pieces of the puzzle that added into your view that functional medicine and your own research has given you when it comes to looking at health and disease? So the, you know, my core interest is brain health. And we now fully grasp that metabolic disturbances underlie the most worrisome of brain degenerative conditions like

Alzheimer's. We've talked about, I've talked about it before on your podcast. It's that inflammation and insulin dysregulation and blood sugar elevation and obesity are all factors that are deeply involved in setting this age for senile dementia of the Alzheimer's type, a disease for which there is no medical treatment, no pharmaceutical treatment. So I'm deeply focused on what are the causes of dysregulated metabolism. I'm running one day, listening to a podcast where Peter Attia is interviewing a Dr. Richard Johnson. And I'm starting to get into the, you know, early on in my run, I'm sort of concentrating on regulating my heart rate and, you know, getting to that magic pace where I feel comfortable.

But I suddenly lost myself in this podcast where Dr. Johnson is revealing this central role of uric acid. So I couldn't get enough of it. So I finally get to my last half mile where I pick up the pace and sprint sort of towards my mailbox in front of my house. I get there and I said, I can't stop. I got to keep going. So added on another couple of miles just to hear the end of the podcast. And then went home and did something I don't think I've ever done before.

I listened to it again. And it provided me a revelationary tool for controlling metabolism. that here was something I had no knowledge of that made perfect sense from incredibly a large number of perspectives, not just the historical perspective, but the application, the interventional trials that have been done, the retrospective studies that have been done, the epidemiology showing relationships, that I just, I was so taken by this information that I did what you would expect, picked up the phone and called Dr. Richard Johnson. and we set up a time to get together.

And I saw the guitar in the background. We were zooming. And that was it. When I saw the guitar in the background of the Zoom call, I said, I got a new friend. And we just had such a great time together. And I've learned so much from him. I'm thinking you might have learned a little bit from me. I don't know.

But I've learned a lot about this gentleman who really has done, you know, he deserves the entire credit for, in my opinion, for revealing the gentleman. this role of uric acid and in our dysregulated metabolism around the world. And he's got two decades of research under his belt. He's very humble. And I was very taken when he wrote me and asked if I would write the fore to his book, which I did. And I actually dedicated this book, a drop acid to him, to honor him just for the work that he's done. This is empowering information beyond measure. This is. is a tool in our toolbox we have never had, but I think moving forward, it is going to really lead to a lot of improvement in people's metabolic health.

You know, we've talked so much about blood sugar, and of course uric acid is directly connected to, you know, the blood sugar and metabolic health, as you've talked about it a little bit earlier. And the interesting thing that, you know, as I started to go down the rabbit hole of uric acid, which is always included in my blood work, but like a lot of laboratory markers, that are out there, they're based on the sort of normal reference ranges for the population. And normal is most of the population is not healthy, is not an optimal health. So what your doctor tells you is normal is not always what is optimal from your stance

in viewpoint and in functional medicine in the latest research. So talk to us about uric acid levels because it's very interesting. There are a few ways that people can test it, you know, some things that you've talked about online. And then they can also ask about it from their doctor, but how to interpret it is not always there. So the data is accessible, and it's nice that it's usually a pretty cheap test, but people don't often know what it means and their doctors aren't often trained in the subject. True, that is an incredibly important point because most doctors are going to tell you that, again, your uric acid level is part of your annual blood test.

as a risk factor for gout. And as such, the norms that have been developed are way too high because they deal with levels above which then you have a risk for having gout or having perhaps kidney stones. And the level of seven or above being considered abnormal relates to, again, risk for gout. And also above seven, that's when uric acid has a much higher tendency to crystallize

and to form these gout crystals that can be painful in your toe, et cetera. So if you have an elevated level of uric acid above seven and you don't have gout and you don't have kidney stones, you have what is called asymptomatic, meaning no symptoms, hyper, meaning elevated uricemia. So asymptomatic hyperurisemia, elevated blood uric acid without having symptoms, is looked upon as being nothing much to worry about. But again, that is only through the context or through the lens, rather, of gouty kidney stones. So asymptomatic hyperurisemia is a powerful risk factor for elevated blood sugar, for elevated blood pressure, for weight gain.

There are a variety of studies that demonstrate that. So it's anything but benign. It's anything but asymptomatic because you just haven't looked at it. You haven't looked at, you know, how it relates to these other issues. So cardiovascular risk, for example, begins at a level of 5.5 and above. So we really need to revise these norms. In fact, there are several studies that have had that in their title, that we need to revise what are considered the normative values for uric acid.

And I think you make a very good point as it relates to functional medicine, and that is that oftentimes we're not so entrenched in the notion. of the so-called normal value that we're really trying to articulate what is the optimal value. The people, you know, normal is what's common. And what's common today is pretty crappy health. And therefore, people who want to be healthy shouldn't look to being normal. I mean, as I mentioned earlier, in eight years, the normal American will be obese if you consider what's common. And that's not what we want.

That's not ideal for anyone's health. So what we're trying to voice is what is optimal in keeping your uric acid level at 5.5 or even substantially lower. And as you mentioned, you know, that's a test most people have had at their doctor's office. And the goodness is you can go online and buy your own uric acid monitor. I did and check your uric acid level with a finger stick just as you might check your blood sugar level.

And I will tell you sneak preview here that we may very well see. continuous uric acid level monitoring in the future, much as we see CGM continuous glucose monitoring, now becoming exceedingly popular, for exactly the same reason. So we can get a dynamic understanding, a motion picture as opposed to looking at a still photo, of what our uric acid level is doing day to day, hour to hour, based upon the foods we eat, the sleep we get or don't get, the level of exercise that we engage. are we in ketosis? How did that affect my uric acid level? And to understand how all of these inputs have an output that you are measuring on the uric acid meter, I think, is really quite profound

in your effort to keep your uric acid level under control. So we note through these examples, and if anybody has had a family member that's had a kidney stone or has been diagnosed with gout, that crystallization, right, is often people have a picture of it or your doctor talks to you about it, that this crystallization is causing a problem, this uric acid buildup that's over here, and now you have the end result, which is like a kidney stone. In the case of heart disease, what's the mechanism of uric acid being elevated and then contributing to heart disease being more likely in an individual? What's the pathway?

What does it make happen more? What does it prevent from happening? It'd be good to tease it out a little bit. Sure. And we can tease it out for heart disease, but let me just say that, What I'm about to describe to you are the same fundamental mechanisms that relate to Alzheimer's, that relate to virtually all of the chronic degenerative conditions that are underpinned by the mechanisms of inflammation, insulin resistance, elevated blood sugar, and all the things that feed into that,

like overweight and obesity and the inflammation that that causes. So we can have the discussion focused on, again, on heart disease. and then simple narrowing of the coronary arteries. But again, those fundamental mechanisms brought on by uric acid are at play across the spectrum of these really pernicious and global issues that threaten our health. So what is uric acid doing? Well, fructose, as mentioned, is metabolized into uric acid.

And that is what we call a feed-forward process. The more uric acid is produced, the more fructose. the more fructose is metabolized because it is a survival mechanism. We want more metabolism of fructose to take full advantage of to make body fat to raise our blood sugar. Fructose in the liver turns on this process of gluconeogenesis, the production of glucose de novo. Why is that important? It's important because it provides blood sugar to power the brain, which is kind of like our ace in the whole. We're not the strongest animal.

We're not the fastest, but we have a big brain that should keep us out of trouble. We can certainly argue that point these days. We don't know what's going on with our big brain. But it's been a survival mechanism for us to keep our brains online. The consequence, however, is that this raising of our blood sugar leads to the pancreas having to work overtime, insulin levels being higher and higher to the extent that ultimately we develop what's called insulin resistance, and we compromise blood supply to our vital organs. Another important mechanism relating specifically uric acid to coronary artery disease, but also

to brain-related disease, is that it inhibits a chemical called nitric oxide. We desperately need nitric oxide to perform two tasks in our body. Number one, it allows blood vessels to relax, so that improves blood supply to the heart heart to the liver, to the kidneys, and to the brain. You know, when the blood supply is compromised, we have things like heart attacks and strokes and problems with kidney function, for example. So that's job number one. We need nitric oxide. Uric acid inhibits it. Number two, lesser known is the role of nitric oxide in allowing insulin to do its job. So higher levels of uric acid increase the compromise of the ability of insulin to do its work.

So this higher level of uric acid, less nitric oxide, we become even more insulin resistant. We starve our organs. And, you know, ultimately with these higher levels of insulin that have to be produced, that in addition augments inflammation. Inflammation, you know, is another feed-forward cycle because that, antagonizes insulin functionality as well. So these, you know, and there's several more, free radical mediated stress is dramatically increased by uric acid.

What I'm saying is the increased production of free radicals. You know, we all think that the more antioxidants that we take, the better because we're limiting this oxidative stress. Oxidative stress is dramatically increased by the presence of uric acid. The other thing that is going on is that because of uric acid's role in enhancing the activity of a specific enzyme called fructokinase, which is important for fructose metabolism, as mentioned, again, we, unlike glucose metabolism, fructose metabolism keeps getting more and more with time. because we know winter's coming. It's a built-in mechanism that makes all those downstream effects happen more aggressively. The production of fat, the storage, the locking away of fat, the production of higher levels of blood sugar.

And one other thing I'll mention is in that process of metabolizing this sugar fructose from, in our ancestors, at least, fruit, we'll talk about how we get it today. something very fundamental happens and it is an energy consuming process. ATP, adenicinitin trifosate, not to be too technical, but that's our energy currency. The three phosphates, when each of them is liberated or taken off of adenosine, it liberates energy. It's the currency of energy in our bodies. So to metabolize fructose, we break down ATP ultimately into AMP, adenosine monophosphate. And without getting too much into the weeds here, that drop in energy is fundamental because it shifts metabolism away from burning energy to storing energy. and to be technical about it for some of the listeners who like that kind of stuff, it shifts us away from stimulating something called AMP kinase,

we'll talk about why that's a good thing, to something called AMP deaminase, or the metabolism of hibernation. It's basically saying make fat, store fat, become insulin resistant, because this is what you need if you're going to hibernate, or we're not going to have food around. Whereas we want to stimulate AMP kinase because AMP kinase says, hey, let's burn our fat. Let's be a fat burning machine. Let's not store fat anymore. Let's not make more blood sugar because we don't need anymore. So what I'm saying is we need to do everything we possibly can to keep this AMP kinase active. We do so, for example, one of the most powerful things we can do to keep that pathway going.

It's a switch. Do you want to make fat store fat or do you want to burn fat? and not make fat. The most powerful thing that we can do to keep that AMP kinase active are things like exercise and staying away from fructose. Those are keys. We have medicines that activate AMP kinase to turn down our liver's production of blood sugar, gluconeogenesis, glucose, like metformin, for example. That's how that diabetes drug works by AMP kinase stimulation. You could do it. Same thing by exercising.

You could take berberine as a nutritional supplement, for example. But that is the side of that switch that we need to keep active. The other side of the switch is this AMP deaminase that sets you up for making so much fat that you're now ready to hibernate for six months. And I would simply ask anyone, is that your plan? Are you getting ready to hybridate for six months? Most people are going to say no. And maybe some are. You know, you're going to hybridate in front of TV and be a couch potato for the next six months. If that's the case and you're not going to eat, then you need to make fat.

But we're just beginning to unravel this science in the context of what it took for us to survive as long as we've been walking this planet. And our primate ancestors too, this incredible survival mechanism that's been in place for, you know, 14 to 17, million years, would we finally look at all of these mechanisms contextually? We realize that that's the problem that we have today. It gets back to this evolutionary environmental mismatch. And I want to give you one more because I think it's really fascinating. Unlike most other animals and mammals included, we humans don't make vitamin C. I mean, you know that.

We don't make vitamins since we have to eat. fruit, we have to take vitamin C or we'll get scurvy, our teeth will fall out and our children will be born naked, all the things that happen, right? So we need a scurvic acid or escorbic acid against scurvy. And you would say to yourself, okay, that's cool, it sucks to be human because we don't have vitamin C. Let's move on. But why? Why is it somehow an advantage? How do we get selected for to have this last step in vitamin C manufacturing in our body be compromised. They're four steps. The very last step in making vitamin C from, oddly enough, glucose is compromised in humans. Well, we have to ask, why would that be a good thing? Because if it were not a good

thing, that wouldn't be a genetic issue that we have, right? We would have selected against it. but yet we selected for it. Well, what is vitamin C? It's a lot of things, but it's an antioxidant. And it turns out that like uric acid, how uric acid induces our mitochondria to pave the way for fat production is through oxidative stress.

That's one of the hallmarks of elevated uric acid, induces oxidative stress in the mitochondria. That is a signal to make fat. If you don't have enough antioxidant, same thing. So that begins to let us understand why it's a powerful, positive selection that we don't have the ability to make vitamin C because this oxidative stress helps us make fat and survive. Not what we need today. In fact, there are certainly some animal studies and some preliminary human studies

indicating that higher levels of vitamin C help us reduce our fat production. So I think where we're going today and what we're encompassing is looking at all of these metabolic nuances of being a human being through the lens of the evolutionary advantage that they offered and now how disadvantageous they are in light of our current environment, meaning our food choices, our other lifestyle choices. So after you on the podcast last time, and you gave us a little teaser about your book that's now coming out, drop acid, you know, link is in the show notes, everybody please get it. It's fantastic. I went on and started Googling and I came across the same Peter Attia interview that you did and listened to Dr. Richard Johnson. We had a conversation with him on the podcast. I don't know when it's going to air in relation to this. But that really opened my eyes, as you've just shared earlier, about the fruit. component and how fructose this thing which was primarily we got through eating whole fruit with so you had the fruit the vitamins you had the fiber which also slowed down the sugar and the vitamin C and the vitamin C and the antioxidate which you just talked about that was central to our evolution into you know human beings just as was cooking and so many other aspects that are there but as you mentioned you keep you've gone back to a couple times is that

the environment change. So with fructose right now, what are the biggest drivers of fructose in our diet? And are there healthy foods that are out there that people are consuming that they think, I'm putting health in quotes, they think these foods are healthy or we've been marketed to that they've healthy, that actually might be a big contributor for a lot of folks who think that they're in the healthy category, but it's a big driver of their uric acid levels being elevated. Let me take a step back. And that would be if we're going to look at answering your question through the lens of uric acid, then by all means, step one to be to see where you start.

I mean, if you call your doctor and say, hey, by the way, what was my uric acid two months ago when I was in your office? And she tells you, well, it was 6.8. That's valuable information. Now that you know that uric acid above 5.5, and there's nothing magic about 5.5, this is, this is analog. 5.6 is worse than 5.5. Doesn't mean that 5.4 is perfect. The only thing that's digital really in medicine is, I think, being pregnant.

You either are or you're not. You're not kind of analog pregnant, right? I think that, so first would be, where are you on that scale? And then what are the changes that you need to make? Our ancestors and primate ancestors, to this day, primates will consume a lot of fruit, pounds and pounds. of fruit as the winter would approach. Bears, for example, eats, you know, pounds and pounds of berries as a stimulus to make body fat to prepare them for hibernation. A hummingbird at times, what is a hummingbird? If you want to have a hummingbird outside your house, you put out

sugar water. Hummingbirds primarily eat nectar. They might eat some insects. That's true. But at times before a long journey, the hummingbird is the fattest animal on the planet. Think about that, the hummingbird. You're thinking of a hippopotamus or an elephant, blue whale? A hummingbird can be 40% of its body weight fat because that's an energy store. So, you know, the notion that fruit containing sugar, that's where fructose name comes from, is a bad thing. I think, again, it's the context. The fruit contained in an apple a day will keep the doctor away. Two apples a day, not a problem. Three to four, you know, you begin to think about it, but the delivery system of fructose along with bioflavinoids, fiber and vitamin C, which help to mitigate against raging uric acid

through a number of mechanisms that we can talk about. I think in that context, then whole fruit is a good thing. Our ancestors would not be migrating and stumble upon trees with fruit juice bottles hanging from their limbs, right? Apple juice, orange juice, whatever. I come from Florida, the orange juice capital, and it's not what you want to be consuming. You don't need 48 grams of sugar in a serving, or, you know, it can be, depending on the size of the serving, as high as 36 grams of sugar in a 16 ounce glass or 12 ounce glass of fruit juice, or 16 ounce glass, rather, that's the same as a can of soda. Why would you want to do that in a way when you're drinking that sugar that it suddenly raises fructose in your bloodstream, triggers this mechanism we've been talking about to make uric acid signaling your body, get ready for winter? Fructose in an apple, five to ten grams, delivered with fiber, delivered with bioflavinoids, delivered with vitamin C.

These are offsets against elevating uric acid. Now, how aggressive do you need to be about limiting fructose consumption? I think everybody needs to take a pause and say, hey, you know, there's fructose in my diet in fruit juice, which I thought was good, but also in the sauces, the various condiments I'm using, you know, out to dinner. You want a piece of fish or whatever it is, but then it's drizzled, the drizzle, right? It's always creative on the meal that you get, oftentimes sugar sweet. And that's why we like it so much.

Why we like sweet is because it's a powerful survival mechanism. There's not a person on the planet who doesn't have a sweet tooth. Do I have a sweet tooth? I absolutely do and you do too. Admit it. We love sugar. We love that taste because it's a survival mechanism. It tells us eat that food.

A, it's safe. In nature, sweet foods are generally not foods that have poison in them. They're not going to kill you. And B, it's been in our interest to eat. eat those foods that are sweet because they are ripe and they are highest in their nutrient value and they're going to help us make fat. So these days we have to do our, we have to take our primitive brain offline and bring online the prefrontal cortex is what you and I talked about last time, get rid of this disconnection syndrome and bring the adult back to make better food

decisions and say that foods that are high in fructose we want to avoid. Now, the only things, the only three things that turn into uric acid in the human body are purines, which are the breakdown products of DNA and RNA, fructose, which we've talked about, and we can certainly talk more about that, and then alcohol. So alcohol is metabolized in almost an identical fashion that fructose is metabolized, almost, you know, peas in the pod. It consumes energy. It down, it destroys ATP. and forms AMP. So it's an energy-consuming event that locks us into this metabolism side of AMP

deaminase, make fat, store fat, increase blood sugar, as opposed to our AMP kinase, which is what we want to activate to make us thinner, burn our body fat, not raise our blood sugar. Alcohol does the same thing. But there are some nuances as it relates to alcohol. So what the research shows is that wine, for example, more so in women than men, is either neutral in terms of uric acid production or may in women be associated with a lowering of uric acid. Not so with beer. I mentioned that earlier. That was your first question, as I recall.

Why? Because beer contains alcohol, but it also contains purines from what? From the brewer's yeast. And these purines are metabolized into uric acid. So that tells the body to make fat. So now you fully grasp why there is a good understanding about where the beer belly comes from. It comes from the fact that beer has alcohol and purines making uric acids saying, you better make fat right now because winter's coming and you're going to need this fat.

Hard liquor as well raises uric acid, not to the extent of beer. But the goodness is there is now beer made without purines to help people with or manage their uric acid. So we're coming along. Two quick thoughts on that. I had shared with Dr. Johnson again, you dedicated the book to him and wrote a lot about his research in there. I was watching this documentary on sumo wrestlers in Japan. And to put on, you know, to put on that sizable amount of weight that they need to be competitive if they're going to be a competitive sumo wrestler, it's actually very tough for them to get that size, especially with the frame of the body type that they might be having in the Japanese

culture. And they have these dormitories, like literally boot camps that people go to, who are sumo wrestlers in training. And one of the ways that they encourage, they've learned just from, you know, hundreds of years, as sumo wrestling has been around, they've learned that this is the fastest way to put on body fat. So in addition to having, you know, six to eight servings of rice throughout the day in these big bowls, right? So they're probably double serving, so they're probably having more. probably are not really contributing significantly to their weight gain. Even though it's spiking their glucose throughout the day? It is.

But, I mean, you know, the other, and that is setting, that, that's taking advantage of then what the fructose is doing. And understand that their use of sugar, table sugar, is, that's 50% fructose. Got it. So in addition to that, so maybe the rice isn't doing that as much. And I have a couple questions on the rice thing is at night before they go to bed, they drink a big picture of beer, and then they go to sleep with basically all that alcohol in their belly. And it was specifically, it's beer, you know, because they found that that's

what helps them put on that massive amount of weight that they need to put on in a very short period of time. It's true, and they're genetically predisposed even more for these issues of waking. You know, when you look through Polynesia and Micronesia, those areas, there is something called Pacific Hyper Eurycemia, where selective pressure of these groups for 3,000 years having these long trans-oceanic migrations to colonize Micronesia, Polynesia, selected out those individuals who survive who could make more body fat on the limited food resources that they had, who didn't need as much water based upon their genetic predisposition. And so it's selected out those individuals to make more fat.

And fat, the metabolism of fat, creates gram for gram water. So having higher levels of fat reserves is what, you know, the blue whale doesn't find fresh water. It makes its own water from its body fat, as do we. Again, we make a gram of water for every gram of fat that we metabolize. We make only, you know, the ratio with respect to protein is about 40% of water. what we can make in terms of water in comparison to fat. So it explains then why in places, in Polynesia, for example, you see incredible rates of obesity

and other metabolic issues like diabetes and hypertension. This is a profound manifestation of an evolutionary environmental mismatch. These people up until 150 years ago were, there are some images of these people, They were thin, robust, and suddenly when our diet was introduced to them, which now they import most of their food, they're not growing it locally, you see the consequences, you know, the incredible rates of obesity. And it has a term Pacific hyperurisemia because the uric acid levels are far higher than we see

in North America and in Europe. Yeah, and percentage-wise, you look at like America Samoa. I mean, the highest body fat percentage of any country in terms of total number of, you know, population that is obese. And, you know, because their bodies, again, as you're mentioning, predisposed to packing on the weight and with the military bases and everything out there, all the American food and the processed food making it out in its direction. I want to go back to rice for a second because I think that, you know, you're an advisor to levels. We've talked about them on the podcast before. We've had Dr. Casey Means on the podcast. And I think as a lot of people

get fascinated, they wear continuous glucose monitors, whether it's from levels or all the other great companies that are out there, they start to pay attention to a lot more of how high, elevated glucose and insulin resistance and how that plays into all different aspects of metabolic health. You said something about the rice earlier, which is you were saying that that may not be, even with that large of a consumption of rice, a primary driver of weight gain when we were talking about the sumo wrestlers. Tease that out a little bit more. How do you think about some of the conversations that we've been having with people using continuous glucose monitors and how,

the uric acid lens would add another layer on top of that because just to bring a little bit more background in this you know often people will see things that are high in purines may not be foods that elevate their blood sugar response immediately that's right immediately immediately right and would love for you to talk about that so then sometimes the thing is like wow okay great red meat grass fed beef you know these foods maybe i'm starting to make more of my diet out of them and less so these spikes that I get from sometimes often some of the carbohydrate sources of things that are out there like rice. So put your lens on there of how you see that world now. Sure. So again, we live in a time of personalized medicine. And it really depends if you're

talking about continuous glucose monitoring. What is your individual response to any food, whether it's almonds or rice or sardines. How does that affect you? And that's why there's such beauty in understanding that biometric of what is your glucose measurement moment to moment. It's such valuable information. But, you know, the notion that the sumo wrestlers are getting fat because they're eating bowls of rice, I think there needs to be more in the equation and you characterize what it is. They're targeting the uric acid path. way to help them become more insulin. All of them are, I'm not going to say all, but I'd be surprised to find a sumo wrestler who's not diabetic or nearly diabetic. I was suspect based on what they're

doing actively to gain weight that, you know, these guys are hugely, are metabolic disasters, basically, and they know it. They're willing to, you know, to pay the Piper up front. But the reason I made that statement is it's going to take more and will having a bowl of rice spike their glucose, it will. But it's in the context of how they've already dysregulated their metabolism through the consumption of alcohol, through the consumption of high-puring foods, and certainly through their consumption of free fructose, meaning not necessarily fruit-related fructose in fruit juices, in beverages.

Once you set the stage for that level of metabolic dysfunction, then when you add in the breakdown products of starch from their rice, elevate their blood sugar, of course it's going to increase their lipogenesis, their creation of fat. But it's not the rice in and of itself. The other factors have to conspire to really set the stage for that level of fat production that these individuals are experiencing. So what I'm saying then is that many individuals who are metabolically intact can afford to have a serving of rice and not see a dramatic spike in their blood sugar levels. And I encourage that.

I encourage through the use of CGM that you determine which are the foods that seem to be spiking my blood sugar. And you'll find that the more metabolically improved you become, the more you're able to tolerate certain foods that perhaps you couldn't in the past, like that serving of rice or like that serving of potatoes. But it's when you're metabolically dysfunctional as brought on by these other indiscretions. That's a kind word. These other lifestyle choices that leverage or are seen through the lens of this paradigm, the fructose to uric acid paradigm, that really caused you to be intolerant of the rice or the other carbohydrate-rich-rich-food

that you may be consuming. So that's why I made that comment about the sumo wrestlers. It's certainly not that, you know, this is a study whereby all they're eating is rice. I think animal research, rodent research would indicate that ad libidum consumption of carbohydrate rich foods doesn't really cause significant weight change in rodents. It is when fructose is given, as Dr. Johnson's research, clearly demonstrated. When he wants to produce glucose elevation or more appropriately insulin resistance and even hypertension in laboratory rodents, he gives them fructose. He adds fructose to their drinking water. Then, intriguingly, what he's done in rodents is he has blocked the uric acid production by giving a drug alopurinol, a gout medication, that then allows

these rodents to have high caloric intake of fructose, but not make uric acid and they don't get metabolic issues. He has repeated those studies in human beings as well and noted the same thing. So we know it's not just the calories, for example, coming from the fructose. It is dependent upon this mechanism of activation of the uric acid that then said it's the danger signal winter's coming, sets the stage for the weight gain, the elevation of the blood pressure, the elevation of glucose via gluconeogenesis, and the insulin resistance. And that is the context in which I answer that question about the rice in the sumo wrestlers. So, and, you know, what is,

in thinking about it, what is so exciting is that this research is going on now around the world. Japan is deeply involved in uric acid research to the extent that they are in fact treating people with certain metabolic issues by giving them uric acid lowering medications. And that research is happening around the world. Places like Turkey and Japan and certainly across Europe, we've in drop acid, we've reviewed more than 400 of these studies. and it's really quite profound how that's going to be translated and now is being translated to the interaction with patients saying that, you know, here's yet another thing we need to consider in terms of getting you back on track so we can help you lose weight, help you get your blood sugar down.

One thing I just want to pin is that as so many people yourself included and my business partner, Dr. Hyman and Casey, who we referred to earlier and many others, are really starting to and have been for quite some time talking about the role of insulin resistance, metabolic health. And then as CGMs have become more available, a lot more people are like tracking it and making changes. And it's like the uric acid piece is another level of sophistication going more upstream. It is. And helping people understand that, you know, we don't want to be in the place where we're, you know, sometimes people get into the pathway of measuring their blood glucose.

they're afraid of certain foods, right? They're afraid of carbohydrates. They're afraid of certain fruits, other things like that. And really what we're talking about is, again, metabolic flexibility and your ability to uniquely be able to handle these foods because regardless of what people think, it's very evident just looking at it. Human beings ate a lot of different things. That's right.

A lot of types of Whole Foods diets, right? As long as it's Whole Foods, they've eaten a lot of different types of Whole Foods diets throughout history. And there's still modern day hunter-gatherers that eat different forms of higher fat or higher protein or lower, you know, or higher carb, whatever it might be. But I want to just pin that point that if you've been hearing about metabolic health, and we've talked about it a lot on this podcast with some of the top experts like yourself that are out there, really you have to understand metabolic flexibility and think uric acid

and metabolic flexibility go hand in hand right together. No question. And again, it's just taking this step back and looking at our evolution, looking at how our day-to-day lifestyle choices play against what we are dealing with. What is our physiology and what is our physiology geared at? Our physiology is geared at survival during times of food scarcity. And when you appreciate that, when you understand that moment to moment your body wants to survive and make the most out of the food that you are going to consume, that we have, as Dr. James Neil described 60 years ago, these thrifty genes, meaning that

We want to make as much fat as we possibly can to keep us alive because, you know, we're hunter gathers. There may be, you know, weeks that we don't have food. And so we have that physiology. And this is a very new nuance to that understanding. It takes us away from being very dogmatic about eat this and don't eat that. Because now we have another lens, as you characterize, to look at our lifestyle choices beyond food, look at what we decide to do, how we sleep, for example. We know that

not getting enough restorative sleep, another time for biometrics, raises uric acid, or at least is associated with an elevated uric acid. That exercise helps to lower uric acid, but not too much. We know that an aggressive period of exercise more than you might normally engage will transiently raise uric acid, why? Because you'll break down muscle. Liberate periods down. Matter of fact, two-thirds of the purines floating around in your body aren't from the foods that you eat. They're from your own muscle breakdown and other tissue breakdown. But even fasting will clearly elevate uric acid. But what the research shows is that that's transient. And that ultimately, as we've talked about many times, the net benefit

at the end of the day, or however many days you fast, is positive that you've done yourself some good. That period of ketosis, for example, ultimately is a good thing as it relates to your metabolism and uric acid and the downstream issue is related to uric acid like insulin sensitivity. While you're in ketosis, your uric acid level may actually go up, as you might expect, when you're catabolic. I want to ask about sleep and exercise. I have a couple questions about those. Before we do, just last couple questions on the food side, we've talked about purines, right? So if you look it from evolutionary history, you know, we talked about fructose and why, you know, when fruit would come in the late summer, the fall, it's designed to fatten you up.

And because, again, winter's coming and you need fat around you to survive. Fat is a storage. It's the energy pack, same as you charging up your Tesla or your iPhone or whatever. It's the energy pack that lets you make it through. So we understand the role of that. Where do you think the role of not the intentionality, of why is it that purines play the role? And surprisingly, you know, some of the foods inside of your book that you'd say that maybe we should be really considering limiting in our diet,

a perfect category is anchovies. So anchovies, typically, you see this term used a lot in functional medicine, smash fish, right? Sardines, anchovies, mackerel, and such and such. Herring. Herring. Sardines and anchovies are high in purines. And what do you, how do you think that fits in because traditionally we've been told, I even wrote a whole newsletter that we're trying to limit the bigger fish that are out there, the tuna, other things, because the plastics that are in the ocean and then feeding on smaller fish, potentially the mercury that's also there too. And there's a lot of reasons why we would want to go towards smaller fishes. How do you, why is it that anchovies and also beef in this instance red meat we're

talking about as well? Why are those foods you think that would have that reaction inside the body. Well, it's a nuance. It's a nuance that we didn't know about before. I mean, you know, there was a time, perhaps if you would have interviewed me 20 years ago, that I would have said, you know, we've got to be on the lowest fat diet that we can be on because, as we all know, fat causes heart disease. We learn. We learn more about what these foods are doing and we change our messaging. You know, people have said, oh, Dr. Prometer told us to be on a low-fat diet. Now he's saying that we should eat olive oil and butter and fatty fish. Gosh, how can you believe that guy?

Because I change my messaging based upon what the science is telling us. Now, I eat anchovies and I eat sardines and I'm not a vegetarian. So I do eat fish and I eat some free-range chicken and I might have some beef. I enjoy that. But I think we get to nuanceing it a bit in terms of quantity as it relates to meat really no more than six ounces a day, which has kind of been my messaging for an awful long time. And to have a couple of anchovies on your Caesar salad, that's going to be fine. But to be binging on sardines, that's pretty powerful in terms of the puring content.

And again, you may get away with it, but that's why you want a home test usuric acid level to see. Am I able to have a can of sardines each day? Is it going to be that big of a deal? might not be. But if you're drinking fruit juice in the morning and you're having, you bet. So it's all about cultivating that program that works for you. And it might be that you're on a pretty good program, but your uric acid level is still six.

And that might be when you say, you know, I'll cut back a bit on meat. I'll cut back a bit on the sardines, for example. And certainly alcohol is a big player. But again, this gets back to the personalized medicine. So it's not cut and dry, black and white. It's nuanced. I would be very sad if I couldn't have anchovies anymore because I really like having anchovies on the Caesar salad.

But if I had, my uric acid level runs about 4.5. So I'm feeling okay about that. But if I was running 6.5, the anchovies would go and I'd be stricter about any alcohol that I consume, for example, and I'd be looking at other sources of uric acid through fructose, through sauces, condomists. I'd be more careful at restaurants, for example. And to go back to that example, you know, you said you have some anchovies, you have some beef every so often, grass-fed beef, you have some free-range chicken. In the case of those different meats that are there, you know, we talked about anchovies, we talked about beef.

What about chicken? Does that, is that something, is it all meats that drive your gas at production? They all do. Yes, to some degree, they all contain purines. As do plants. Plants have DNA and RNA, and so they can be a source of purines. And matter of fact, there are certain plants, the cruciferous vegetables, for example, are pretty darn high in purines. If you look at the tables that were given to gout patients over the years, they were told don't eat broccoli, for example, don't eat mushrooms.

Why? Because they're really high in purines. Well, that's a little bit myopic. It's one thing to say, yes, they're high impurions. But then to make the leap to say, and they're going to raise your uric acid and you're going to have gout in your toe, that's not fair. Because if you look at what the research has shown in terms of looking at large populations using what are called food frequency questionnaires, those individuals who consume the highest level of those purine-rich vegetables actually have lower levels of uric acid. And we're back to fiber and vitamin C and bioflavinoids that help lower uric acid. So it turns out to be a net gain for an individual to eat those vegetables. So yet those vegetables have high purines.

Dr. Pearl Motor didn't say you shouldn't eat broccoli and broccoli sprouts and mushrooms. They're on the list, eat those foods in abundance. It kind of reminds me about the whole conversation about salt. There's so many people that are out there that have hypertension and they're told to, and I know there is a connection with salt and the concentration of salt, and I learned that a lot through your work and Dr. Richard Johnson's work. But interestingly enough is that they're told to fear the little bit of seed salt that you might add to a salad or to some roasted vegetables that you end up making,

but not understanding that for most people who are eating a processed food diet in America and are struggling with hypertension, high blood pressure, they're getting the vast majority of the salt, not from what they add into foods, but from the processed foods are out there. And the other thing they add is sugar. Right. You know, close to 70% of the processed foods in America have added sweetener by and large. It comes from something called, who guessed it, high fructose. Don't want that corn syrup.

So this is corn syrup that has at the minimum 55% fructose. And why more fructose? Why was that created? You know, that was Dr. Richard O. Marshall in 1957 developed that technology, University of Oklahoma, because it's cheap and fructose is far sweeter than glucose. So the higher level of fructose, the less you need to use to sweeten your food, the better is the profitability, right? So, but let me get back to the meat question. And then we'll talk about salt in just a moment. The biggest issue as it relates to meat are the organ meats. They are really high in purines. That would be eating liver and kidneys and pancreas. I mean, I would never, I just never gravitated towards those foods, but they're probably good for you in some regard. I know liver has, you know,

B12, et cetera, but by and large, those are the really high purine foods. And venison and gaming meats as well, ostrich have high levels of purines. Now, as we relates to salt, salt, anything over about 11 grams a day then creates a threat through the mechanisms that we've been talking about today. Salt specifically when it is raised in the bloodstream activates two enzymes. The first is called fructokinase. And what does fructokinase? That's step one in the metabolism of fructose into uric acid. So we want to limit that. Matter of fact, there are pharmaceutical companies that are now understanding this relationship between fructose and obesity and making body fat are now creating drugs that will turn off this enzyme fructokinase higher levels of sodium in the

bloodstream turn on this enzyme the other thing that higher levels of sodium do they activate another enzyme called aldose reductase that'll be on the quiz you better remember that alus reductase actually converts your blood sugar or glucose also into Fructose telling your body, winter's coming. Make more fat. And every time I say this winter's coming, I keep thinking of Game of Thrones that we're waiting, you know, but it's a different winter. Going back to the organ meats, you know, this is where I think that the people that are

listening naturally, again, we have to understand, and this is why we have to be wary about following anything that's too sensational. Right. One food or one style of eating is the answer or the destruction of humanity. We already know that largely, we're already doing that on our own from a human level, you know, 11 million people you are dying from chronic diseases that are directly related to ultra-processed and processed foods that are out there. That's like we know that that's the worst thing. And generally if you're in the category of primarily focusing on whole foods and not

drinking sugar, you're in like already a good boat, right? Now in the category of organ meats, we've had people on the podcast before, friends, colleagues of both yours and mine, people like Dr. Terry Walls, who have talked about in their protocol, like the Walls Protocol, how organ meats in a target fashion. She's not basing the entire portion of her diet around it have been a central part of what she's seen that has been helpful to people that are on the walls protocol. So put this in terms of context and quantity. And again, things are evolving and we're all learning together. And your book is a part of that process that we may completely, you might start seeing a lot more functional medicine doctors and integrative doctors talking about uric acid. I suspect that

that's going to be the case. So with organ meats, put that in context with everything else that's out there. If we've heard some of the benefits that are there for organ meats, but we're talking about them being ultra-high in purines. Yeah, just want to see how you sit with that. Well, I spoke with Dr. Walls last week, and we talked about diet, as you might expect, and I think her work is absolutely outstanding. And there is obviously upsides to eating organ meats. As mentioned, there's some good things going on in organ meats that are good for us, nutritious. But again, this isn't black and white. It's nuanced about, well, what might the downsides be if we go overboard on it?

Now, Dr. Walls likes organ meats because now we're not eating carbs. It helps a person get more into a ketotic state, which, you know, from her perspective, is a good thing. It certainly speaks to a paleolithic sort of approach to eating, which is what her new, you know, diet is really focused on. And it might be you can have all the organ meats you want if your acid is in the normal range or the optimal range, as I prefer to say. So if somebody was eating organ meats but they're measuring their uric acid and they're in the optimal range of that, you know, that five number and you mentioned for you, it's you're usually around like 4.5, you said? 4.5, 4.6, yeah. Yeah, 4.5.4.6. You're okay with it. Oh, I would, I would say yes.

I mean, you know, there are other considerations with respect to eating a lot of meat in general because you tend not to get fiber into your diet, which is, you know, there's no fiber and meat and that can be an issue. But, you know, I don't think we're talking about black and white. We're talking about optimizing. We're talking about yet another lens to look at. That's the beauty of what we call the love diet, lower Uric values. The beauty of it is you can be vegetarian.

You can be, you know, pure paleolithic. like. And you can still make these subtle changes and nuance that dietary approach through the lens of keeping your uric acid level in check. But, you know, to get back to a point you made earlier, what's it going to take? Is this just a functional medicine sort of approach who is going to embrace this? I think not. I think with the level of research going on around the world, there is already traction in the understanding of uric acid. And for your viewers who are going to present this information to their treating physician, there may be some skepticism. And I would say, you know, the simplest thing is ask your treating health care provider to do one thing, and that is Google two

words, metabolic and the word uric. You don't want to Google metabolism and uric, because then you'll get uric acid metabolism, and you don't want to look at that. You want to look at metabolic, because then you get metabolic syndrome and all that is metabolic and uric. And you could look at PubMed. I mean, you know, the number of literature citations is, is overwhelming. And to be fair, people tend to be down on what they're not up on, meaning that if they've not been exposed to this, I mean, you, after speaking with Dr. Johnson, as you said, went down the rabbit hole. And I'm sure you uncovered incredibly vast resources of information related to this new concept. And the beauty of it is it plays into our understanding of the mismatch between evolution and environment. We've

got to bless this evolution. We've got to praise it for all that it does for us, that it has cultivated this incredible human body that is so resilient and adaptive to some degree. Is it perfectly adaptive? No, to changes in an environment? No. But as you mentioned, we are omnivorous. We can tolerate a lot of different types of foods provided those are foods that we've been exposed to in the past. And I would submit that the crap that we are exposed to now is nothing like the human body has ever had the opportunity to adapt to. And it calls to me back to that article I wrote when I was 16, you know, what about us with this outdated machinery that we're not going to adapt quickly enough to deal with the degree of processing of our foods? The whole notion of the term

food manufacturer. I mean, that is an oxymoron. Food isn't manufactured. We don't make food. We can grow food. We can find food. We can cultivate food. But the idea that food comes from a factory and our scientists can outsmart

nature and create these things that we then consume, I just don't think that's anything that we can expect is going to happen in our lifetimes. You recently on social media wrote this, what I would call it like a love letter to honey. Oh, yes. One of the most popular posts ever.

Talk to us about, honey, how you used to see it and how you see it now in the context of everything related to Eurogassie. And, you know, my mission is to be as forthright as I possibly can be. I appreciate that about you. And sometimes. That's what we should all really step into. Yeah. Sometimes it seems to run counter.

But yet we talk about it anyway. And it was an Instagram post and I said, honey, I'm sorry. And then I went on to explain why. And it went crazy because I think people thought I was apologizing to my wife. And so they thought, I'm going to go, he's going to tell us what he did. And so I have been negative towards honey, dare I say, castigating honey over the years because of its high fructose content. And, you know, sort of. It would be lumped in the boat.

Sorry to cut you off. It would often be like sugar, sugar, sugar. And people would kind of put it there. But specifically because it had fructose. Basically, honey has high fructose. And it turns out that the research relating honey to metabolic issues and diabetes shows that it's not related to increasing risk and may actually be therapeutic. That's what the literature shows.

I kick and scream about that a little bit because it doesn't fit. It doesn't fit at all. But I'm going to be here and report it because that's what the science talks about. It's counter to my intuition. but nonetheless, that's what they've said. And now we have to ask ourselves, why is it the bioflavinoids? Are there other ingredients or ingredients, other things that honey contains that make it ultimately salubrious?

I don't know. That's obviously what's going on. So I'm going to say that having a little bit of honey in moderation is a good choice. Now, having said that, and even higher and more, and clearly honey is not generally a processed food. But the processed food that is lumped in with honey is agave. Gave is clearly, fairly highly processed, and there's nothing helpful about agave. Probably the highest fructose source you can consume. And there's no redeeming value of agave. Now, I may come on your podcast in a year and a half and say, hey, honey, I mean, agave, I'm sorry. Probably not. Probably not. There's no redeeming value.

at this point in time for agave, though it is called nectar. I mean, it's nothing, you know, the food of the gods. We need to avoid agave and all other so-called hidden sources of fructose, and there are many. So on that topic, there are a few other types of sugars that are coming out there that are getting a little bit of traction. And just would love to ask you before we talk about a few other plant compounds and potential therapeutic benefits of some things that can help us bring uric acid down. So, alulose is a sugar, is a sugar-like thing. I'm just saying sugar, but it's not actually sugar. As far as I can understand from having looked into it, is that it's an extracted compound

that really comes, primarily it's coming from, they're using corn, as I understand it. They're using fructose from corn. They're using fructose from corn. Can you imagine? Right, which is scary for a lot of people. It is scary. And yet, what do we know about alias? I know that alulose, the research shows that it is beneficial for insulin resistance, that it has positive effects on blood sugar.

You know, generally, my hope is to help people cultivate decreased exposure to sweet taste so that they don't crave it as much. You know, that may never fully undo our desire for sweet, which is hardwired. But if people do need a sweetener, I think alulose is not a bad choice. Right. It's getting some traction. There's some healthier for you candies, other things like that that have alulose in them. But I think that this goes back down to some of the science around also just dopamine stimulation. And we don't want to constantly be going throughout the day, you know, having a super sweet latte to a super sweet orange juice to a super sweet, you know, after lunch, you know, snack to another super sweet. And we're constantly spiking our dopamine throughout the day. And we're never able to. really sort of appreciate the joy and the beauty that comes from just having, you know, a small bowl of blueberries or an apple or whatever it might be. Exactly. And again, you know, that is so fundamental to the standard American diet and that is sweets

at every meal. But I will say this is what I've been doing. Since I've been talking so much about CGMs, a lot of people find that one of the first things that they do starting off their morning that spikes their blood sugar and keeps it going throughout the day, even a lot of healthy people, is they don't realize how much the the almond milk that is sweetened that they're having, or many people are like, I don't have sweetened nut milk. I have oat milk. Right. And oat milk has a ton of sugar that's included in the manufacturing process. That's right. So we've gotten everybody to switch over to, you know,

unsweetened almond milk. And sometimes people have that sweet taste in the morning. And I've said, you know, try alulose. So far it seems, and again, you may come back on here next year and tell my audience to maybe potentially avoid it. But it does seem that that is a, I, I, I, I, I, I would rather steer people if they're going to make a homemade latte, go with unsweetened almond milk or seed milk. And if you want a little bit of a sweet taste, you can add in some allulose or potentially maybe even a little bit of honey. Perhaps a little honey or, you know, even monk fruit.

Right. Even monk fruit, which I love. Yeah, I don't. But all in the context of like we need to really be looking at our uric acid levels and see how this. That's right. And so just to take apart a little bit deconstruct what you see. said, you know, you get up in the morning and you want to have that coffee beverage, whatever it may be.

And I think people think that, you know, if they're going to go to the coffee shop and while we, you know, there's a lot of research on the upsides of coffee, as a matter of fact, lowers uric acid. One new study came out just yesterday showing that coffee drinkers have a significant reduction in risk for Alzheimer's. And having said that, it's not news. We've known that for quite some time. But it doesn't mean that a triple mocha, frape latte, whatever that thing is that comes in a great big plastic thing with a container with a straw sticking out. That's not coffee.

That's not your morning coffee beverage that we are talking about. We're talking about black coffee. The other thing is in terms of starting your day, your breakfast, there's a lot of merit to putting that off, the breaking of the fast, the break fast, to putting that off. I guess time restricted eating would be another top. perhaps for another guest, but the notion of protracting that period of time before which we then consume food, I think there's a lot of merit to that, and even offers an offset for improved metabolism that might be compromised by having a high uric acid. What did I just say? That if you can engage the notion of time restricted eating, compress the amount of time during which you eat food

in a given day to eight or perhaps even 10 hours, that the, the, the, the, Upsides for your metabolism might offer an offset to you if, for example, your uric acid might be a little bit elevated. Yet another powerful tool. We actually talk about time-restricted eating in the book. As we wrap up here, quercetin. Talk about quercetin and some of the reasons that you highlighted that in the book and some of the research that's related to quercetin, which has gotten a lot of attention in the context of COVID-19 and people paying attention to it. How does it relate to uric acid?

Well, you're right that Quercetin has been on a lot of people's radar screens for quite some time because it's anti-inflammatory activity. It's antioxidant activity. It is a bioflavinoid that's rich in various foods. Probably the richest source in nature would be onions and in particular red onions. I've been interested in Quercetin more recently because of its senolitic activity or purported senolitic activity. in other words, the ability that quercetin and others similar bioflavinoids have, like ficetin, for example, to help our bodies rid themselves of senescent and perhaps not as fully functioning immune cells. But in the context, and this is really very exciting, of uric acid, quercetin shines, quercetin is almost or perhaps equally as powerful as the pharmacy.

I mentioned earlier called allopyrinol in terms of targeting a specific enzyme called xanthine oxidase, which is fundamental in the production of uric acid. So we are able to limit the production of uric acid by using quercetin. One study of 22 young males with borderline elevation of uric acid done in England demonstrated that 500 milligrams per day in two weeks was able to lower their uric acid without any other dietary change in comparison to placebo by 8% in just two weeks. That's big time. So quercetin and 500 milligrams a day, Luteolin, another bioflavinoid, 100 milligrams per day. Luteolin is the one that is in fact demonstrated to be as efficacious in targeting that xanthine oxidase enzyme and lowering uric acid in comparison to a drug, alopurinol,

is a gout drug. So here you can get things at the health food store that'll lower your uric acid. Of course, we call these supplements, meaning that they are supplemental to the big program, which is cutting off uric acid production at its source, mainly getting rid of the fructose, the free fructose in your diet, the fructose that's added to your sauces, your condiments that's, you know, as I mentioned, more than 60 to 70 percent of packaged foods. in America. And even fruit juice, though we think, oh, I'm getting my vitamin C. I'm going to be healthy. I'll drink a glass of fresh orange juice every day. You want to avoid that. Eat an orange. Eat an apple. It will keep the doctor away. It's powerful information. And it's really just another

layer that we can add to the things that we're up to. And for a lot of people, I think it's going to help connect the dots about maybe how some aspects of how they were trying to personalize their diet wasn't maybe working for them because they had liquid form of fructose in their diet as a as a as a as a big driver or they were maybe focusing on you know too many high puring foods and we're just a little bit of optimization we can start dialing these things in is there a brand of uh your uric uh acid monitor meter that you like something that you recommend or is it just i use a brand called U-U-U-U-U-S-U-R-E. And they're available everywhere. And are they typically like a little, like a finger-prick sort of?

You bet. And the trick that I've learned for, I'm not keen on the finger prick. That's why I like C-G-M. But if you put it, the little lancet right under your thumbnail, it works like a charm and you don't, and you don't even feel it. And how much variability do you see? I mean, obviously, you're not eating a lot of fructose that's there, but if you have people that you're guiding or people that you've gone and seen on that journey, how much variability will they see in a day? I think that people are going to see a lot of variability, not within the day per se, but day to day. And so it's highly variable based upon, you know, levels of physical activity and the amount

of fructose consumed. Liquid fructose will right away raise uric acid. I mean, that's what, like I said, that's what is designed to do. That's how it plays out in your physiology. That's what, you know, that's the signal. You're suddenly eating a bunch of fruit to get ready for winter to make fat. And boy, that mechanism is activated. The alarm system is lit up.

The board is all on lights. Winter's coming. We've got to make fat. You shift your entire metabolism. Everybody comes on board. All the little cells in your body are starting to get dialed in that winter's coming. And clearly, we need to do everything we can to turn that off because there's no need. It's just, and that's the centerpiece now.

So it's really very, very empowering and very exciting. And you're probably going to close by asking me, hey, what's next for you? And I don't know how I'm going to answer that question. Last time I said uric acid, but I think this is going to be with us for quite some time. And I think what happens moving forward over the next couple of years is we're going to learn a lot more about it. And there'll be a lot more authors that are going to explore it. You know, if you want to learn about something, if you want to understand something, you read a book about it. But if you really want to know something about a topic, you write a book about it.

And then you know, gosh, you know, the level of understanding that you get. And it's just so very satisfying to have this novelty in our lives that we knew nothing about. And most importantly, how this becomes such a powerful tool for people who've struggled, who, you know, have been on whatever the popular diet is of the day. And still there's a missing piece and they know darn well that there is something out there that they just haven't learned about yet. And now they can know. And maybe this is it. I think it might be that missing piece of the puzzle for a lot of people.

Or maybe they're just borderline hypertensive to the extent that they do have to take a low dose of a blood pressure pill every day. And this control of blood pressure brought out by lowering uric acid might be enough to help them. get off blood pressure medications, many of which raise uric acid. Think about that. Elevation of blood sugar, or rather elevation of uric acid, leads to increased blood pressure. And various blood pressure drugs are raising uric acid, like the diuretics, the water pills, the beta blockers, for example. These are drugs that increase uric acid, which tells your body to raise the blood pressure.

So you're really chasing your own tail as it relates to, treating your blood pressure with these drugs that raise uric acid. Other drugs like proton pump inhibitors taken by 14 million Americans dramatically increase uric acid have been strongly related to risk for Alzheimer's and stroke in a powerful publication in the journal Stroke. And now we have a mechanism whereby they may be related. We know that elevated uric acid, as I've mentioned to you, compromises nitric oxide. that means poor blood supply to areas like the brain.

One would expect increased risk of Alzheimer's, increased risk of stroke. How incredible it is when you think about that mechanism, that compromised blood supply, which we know happens, for example, in the Alzheimer's brain, could be related to this compromise of nitric oxide brought about by uric acid. How do we override that nitric oxide story? What is the prototypic drug that increases nitric oxide? It's Viagra, increases blood flow. That's why men who have erectile dysfunction take Viagra.

A study published this morning looking at several million people. You saw that. Showed that those who regularly took this drug that increases nitric oxide had a 70%. It was associated with a 70% risk reduction. for Alzheimer's disease by increasing nitric oxide. Keep in mind, elevated uric acid compromises nitric oxide. It's not what we want. Two things it does. It messes up how insulin works and it decreases blood flow and neither of which is a good thing. Right. You don't want to be in the position where you have to take Viagra, you know, because that's a sign that probably there's not enough nitroac nitric

oxide production that's there, but you're talking about the beneficial components of how increasing that nitric oxide production, if you are in a place, nothing wrong with people needing to take Viagra, that the potential, what mechanism is it taking advantage of that would also lead to other benefits? That's right. And let me finish with one last point that I think may have traction as we do talk about erectile dysfunction. That always seems to be an area of interest.

And that is that those individuals with the highest level of uric acid, there's about a 38% risk increase for erectile dysfunction. Why would that be? Nitric oxide is probably the explanation. Fascinating. Very fascinating. Well, I know we've been going for almost about two hours here. So, Dr. Perlmutter, I want to be respectful of your time. There's so much more that we could have covered, but that's why you wrote the book.

There you go. So that people can go a little bit deeper into it. We'll have the link to the book in the show notes, drop acid. Please pick it up. It's probably one of the most fascinating books that I've read this year, and I'm not just saying that. Thank you. It added a whole new understanding. I mean, I've been very honest with my audience about my own changes in my diet.

I was doing a lot more of like a keto-type diet. I was having a lot more saturated fats that were in there. I had a microbiologist come on the podcast and talk to me about some of the factors of saturated fat leading to potentially aggravating leaky gut. When I read this book here, and I understood that in some cases read me, and the uric acid levels might also be a factor that's causing some leaky gut for people who have gut problems, issues that added another layer to my own personalization of the diet and having since pulled back on some of the saturated fat, which probably also was high

uric acid content foods, and doing a little bit of gut restoration, I feel so much better. The redness in my skin has gone away, but there's just so many layers like that that I think that everybody can take away from diving deep into the bottom. It's all about fine-tuning. And it's not about, you know, locking into one dogma. Totally. And it's about fine-tuning and being flexible moving forward that, you know, the messaging might well change. And, you know, we didn't get to talk about the effect of elevated uric acid on the gut and on gut permeability.

And why now there's research showing that fecal microbial transplants are helpful in reducing gout flare-ups. So there's a powerful relationship there between what goes on with respect to the microbiome and uric acid. So you're exactly right. Anywhere else you'd like to send our audience to learn more about the world that you're up to in addition to the show notes about the other. I think the clearinghouse is Dr.perlmutter.com. Perfect. They start there and there's plenty of information. Dr. Perlmutter, always a fascinating conversation.

Thank you for coming in. And it was a pleasure to have a conversation. It's always great to see you. I'm looking forward to next time. Who knows what we'll talk about? Who knows?