Lower Uric Acid to Prevent Degenerative Diseases, with Dr. David Perlmutter

Having a higher uric acid was a superpower for our ancestors. And in the context of today, these are things that are at the center of metabolic syndrome and therefore at the center of the most common causes of death on our planet today.

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Hello and welcome to this episode of the Five Journeys podcast. Live like youe Matter. I'm Dr. Wendy Trubo. My co host is Dr. Edward Levitan. And I'm always saying this, but our guest today is Dr. David Perlmutter. And I am so psyched to interview him.

Me too. Me too. Me too.

Well, I'm psyched to be here.

Delighted. So let me tell our listeners, I don't know who'd be listening to our podcast who wouldn't know about you, but let me tell anyone who's listening. He's a board certified neurologist. He's a fellow of the American College of Nutrition. He's a frequent lecturer at symposia sponsored by institutions including the World Bank, Yale, Harvard. He serves as an associate professor at the University of Miami, Miller School of Medicine. I've seen him speak, he's brilliant. He's also a five times New York Times bestselling author who has published books such as Brainwash Grain Brain, Brain Maker and his latest book, Drop Acid. So of course you have to tell us, like, how'd you come up with that title and welcome.

Well, no, first I gotta tell, tell everybody that I'm a groupie.

Yes. I'm a groupie of Alessio and you're. He's a groupie of.

Well, there you go. The title came from, you know, wanted something snappy, attention getting, and it has to do with dropping acid. The specific acid we're talking about is something called uric acid, which is, you know, what we all learned about in relationship to things like gout and kidney stones. And now we know, you know, brand new research that was just published in 1898 reveals that uric acid's a much bigger consideration than just related to the gout in your big toe and kidney stones. So. So it's a fascinating story. Beyond that, what I find so intriguing about it is it opens the door to have a new lever to Pull in terms of helping people regain their metabolic health.

So let's talk about that. What is uric acid?

So uric acid is, we've previously considered to be sort of a metabolic end product or waste product that when we would digest certain things like the DNA and RNA in the foods we would eat, for example, that became what are called purines, that ultimately that would form this acid called uric acid, and it would accumulate and we would ultimately excrete it through the kidneys. And, you know, you guys learned it, I learned it. And if it wasn't excreted appropriately or in good enough quantity, we would develop these crystals that would form in various parts of our bodies, like the toe, like actually the coronary arteries and even the prostate gland. That's kind of new information. So we considered it the end product. We didn't pay it much heed. Maybe we spent one lecture in pharmacology to learn how to get rid of uric acid, for crying out loud. But we now recognize that it is. We've known for a while, for decades, that we see it elevated in conjunction in association with things like hypertension, insulin resistance, full blown type 2 diabetes, and other metabolic issues. And we thought, well, isn't that interesting that uric acid happens to be elevated in these conditions, Therefore, these people are at risk for gout. But in more recent years, we've learned that it isn't just happening to be elevated in these individuals. It's actually playing a role in causing the very metabolic issues that I just mentioned. So one study that came out of a paper that came out of a collaborative study from Japanese and Turkish research researchers called uric acid in metabolic syndrome from innocent bystander to a central player. And that is a major shift in how we conceptualize uric acid, that it's not just happening to be elevated, but it's actually leading to these issues that we dreadfully fear, that we really recognize are playing such a central role in chronic degenerative conditions that the World Health Organization is telling us are the number one cause of death on our planet right now. Not Covid, not trauma, not war. It's the chronic degenerative conditions, the diabetes, the Alzheimer's, the coronary artery disease, et cetera. These are at their core caused by metabolic mayhem, if you will. And now we recognize that uric acid is playing a functional role in leading to that metabolic mayhem. Therefore, we should ask ourselves, well, why is uric acid so elevated these days, number one? And once we understand that, then how do we implement strategies to help People bring their uric acid levels down to better levels, to safer levels. We had said to people over the years that, you know, a normal uric acid level is anything under 7 milligrams per deciliter. But again, that number was derived in the context of gout, meaning that above 7, you are at much higher risk for gout. Above 7, uric acid tends to precipitate in the blood and form the very crystals that lead to things like gout, etc. But now we know that our goal should be actually much lower levels of uric acid below 5.5. Above 5.5, we start to get into various mechanisms that are dangerous to the human body. And we'll talk about those in specific, from the perspective of they're really cool, A and B, we can do things to help in those mechanisms that can help people be healthier.

I have a million questions, I have.

A million questions, but go for it.

All right. Age before beauty, I guess. So you referenced, now you kind of referenced this is a problem. Now, has it always been a problem, we just didn't recognize it? Or is there something in our environment that's altering our response to uric acid and making it much more harmful, prevalent?

Well, the response to the elevation of uric acid is nothing new. I mean, that's a genetically programmed part of our physiology. And we'll get back to that in just a moment because it actually is a survival mechanism. Who knew? But the, the sudden elevation of uric acid that we see began around the 1920s when we began dramatically increasing the amount of sugar in our diets. You know, traditionally, if, if you were trained to help somebody from a nutritional perspective, to give them tools to lower their uric acid, you would put them on what's called a low purine diet. And to this day, when you go on the websites of some of the very popular so called clinics that have fancy names, you'll see them emphasize that, you know, low purine diet is the way to go for a gout patient. Well, we're now even seeing those websites start to talk about sugar, and in particular the sugar fructose. Fructose is directly metabolized through the action of several enzymes, most importantly, fructokinase, to become uric acid. That's the end product of fructose metabolism. Metabolism in your body, it follows the exact same metabolic pathway as alcohol. So both alcohol and fructose undergo several transformations to become uric acid, the purine, by virtue of the foods that we eat, or the breakdown of our own tissues is a bit of a different pathway. But interestingly, the final step, enzymatically, is the action of an enzyme called xanthine oxidase, so that if you can block or slow down this enzyme, xanthine oxidase, you will lower your acid. That's where the gout drugs work. That's where quercetin works, for example, is by reducing the action of the final step. Now, to answer your question, I'm not sure you meant to pose it this way, but it does open the door for me. And that is, why does it happen? I mean, why does uric acid do all of these things when it's elevated in human physiology? And that is because elevation of uric acid, strangely, is a survival mechanism. When uric acid is elevated, it became a survival mechanism for our very distant ancestors. We used to have enzymes in our bodies called uricase. When I say we, our ancestors, our primate ancestors had uricase enzymes such that when they would form uric acid in their bodies, then ultimately uricase enzyme would break it down into something called urea and allantoin. But around 14 to 18 million years ago, during a time of food scarcity, there was a very powerful selection pressure on our ancestors to select out those who could survive on minimal amounts of food and, to a lesser extent, minimal amounts of water. And it turns out that having higher uric acid was a good thing for them. So this was a population then that selected for higher levels of uric acid, such that with time, the uricase enzyme, basically suite of enzymes, actually disappeared in those who survived. Having a higher uric acid was a superpower for our ancestors. Why? Because it caused them to make a little bit more body fat. It caused them to reduce the oxidation or the utilization of body fat as a fuel. It caused them to raise their blood pressure during times of water scarcity, led them to be a little bit more insulin resistant, such that they would have a slightly higher level of blood sugar, such that they could power their brains during times of food scarcity and find food and avoid being eaten by other animals, what we call starvation and predation. They could avoid those things because they were able to power their brain. So in the context of our distant ancestors, having this higher level of uric acid was good as survival mechanism because they raised their blood pressure, made them fatter, made them insulin resistant. And in the context of today, when we have this mismatch, we don't have food and water scarcity, raising our blood pressure, raising our blood lipids, raising our body fat, reducing mitochondrial functions so that we don't burn as much energy reducing oxidation of fat as a fuel source. These are not good things. These are things that, you know, are at the center of metabolic syndrome and therefore at the center of, as mentioned earlier, the most common causes of death on our planet today. So we have to look at insulin resistance and becoming hypertensive and diabetic in the context of our ancestors. That was a good thing. Who knew that on your podcast today, I'd be saying diabetes is a good thing in the context of our ancestors today, of course, you know, it's pretty much the center of so much evil as it relates to other things. Heart disease, some forms of cancer, and as much as quadrupling an individual's risk for developing Alzheimer's, a disease for which we have no meaningful treatment, affecting 6 million Americans around today. And that number expected to go up dramatically in the next eight years as we move towards 2030. But that said, that's the overview of why we're in the fix that we are. Because we're suffering the consequences of what we call an environmental evolutionary mismatch. We evolved this ability to have higher levels of uric acid to survive in the context of food restriction, the ability that we have to create uric acid from fructose, or eating fruit that we might find then making more body fat. But that's certainly not what we want to be doing today.

I had a question about fruit there, because that basically sounds like fruit has fructose, so you shouldn't eat fructose. Is that like the line that I drew from that that I should or shouldn't be drawing?

And I'm glad you brought it up. I. I can't say, I really can't say that I've ever done a podcast in the past two years where that question hasn't been asked. It's a terrific question because first, the food frequency studies show that people who eat modest amounts of fruit actually have a lower uric acid lower. Second, fruit, oddly enough, in its whole form, doesn't contain much fructose at all. An Apple has about 5 grams of fructose in comparison to 36 grams of sugar in a can of soda, for example, or a 12 ounce glass of orange juice. So there's nothing natural about fresh squeezed orange juice or that you buy in a carton. Our ancestors wouldn't stumble upon a grove of orange juice with cartons hanging from the limbs. Right?

What's moderate for fruit intake? When you say moderate, what's moderate in your world?

An apple or two a day A handful of blueberries, some strawberries. You know, there are certain fruits that have higher amounts of fructose, like watermelon and other types of melon, like cantaloupe and honeydew. But. But have some fruit. But, you know, when think about a bear getting ready to hibernate, what is that bear eating all day long? Berries, you know, blackberries, loganberries, salmon berries, whatever they are, they're just gorging on those berries. So that's not a modest amount. And what's happening in that bear is that that fructose is becoming uric acid. And it says to the bear, winter is coming. Make as much fat as you can because you're going to hibernate. Now, I use that example when I talk to people, hoping they're not getting ready to hibernate. And if, if they are, then you better make sure you pack on some pounds if you're going to go and, you know, into your apartment and hibernate for six months. Obviously, you know, it's a bit of a joke, but. But it really gets to some very, very fundamental mechanisms, because that level of elevation of uric acid that people have and that bears have, people have day in and day out, bears have as they're preparing to hibernate. That elevated uric acid inhibits an important enzyme pathway in the human body called ampk. Shall we talk about that? I can break it down, make it simple.

Yeah, definitely.

So uric acid in our physiology can be broken down by AMP kinase. So that can be what helps to break uric acid down. Actually, it's not the uric acid, it's actually the AMP part of uric acid's metabolism, to be fair. So when fructose is initially treated by its enzyme, fructokinase, ATP, which is an energy molecule, is ultimately broken down to adp, adenosine diphosphate and ultimately to amp. So the question is, how is AMP dealt with? Well, amp when it's broken down by this AMP kinase, and people will hear about that, so we'll talk about amp kinase or YouTube videos about it when that happens. AMP kinase activation, to break it down, does some important things. It tells our bodies that the hunting is good, and it says we don't need to turn on the production of glucose in your body. So it helps keep glucose under control, it reduces appetite, it helps with cellular breakdown, so we can rid our bodies of accumulation of debris, and it helps the body use fat as a fuel source. All that sounds really good, doesn't it? And so we really want to Keep our AMPK lit up, because when AMPK is active, we're going to be thinner, we're going to have better blood sugar, we're going to just generally feel pretty well. But it turns out that AMPK has an evil twin. Who knew? And this is AMP deaminase. And it's AMP deaminase that is dealing with this adenosine monophosphate, the breakdown product of fructose metabolism. And when AMP D is activated, then it tells the body, whoa. Make fat, store fat, make sugar, decrease your mitochondrial function so your energy burn is less to get ready for winter or food scarcity, as the case may be. Uric acid elevation turns off the good guy, the AMP kinase and favors AMPI deaminase. So that's one of the ways by which uric acid is so influential in our metabolism. It's basically telling us to prepare for either hibernation or for upcoming food scarcity. And that's why we've really got to do everything we can to not elevate and uric acid in our bodies. Now, the big player, if you ask me, what are the top five things to think about in terms of elevating uric acid. First would be fructose. Second would be a sugar called fructose, and third would be fructose. Fourth would be purine rich foods like organ meats. And five would be alcohol. What I'm saying is it's all about the sugar. In our diets, table sugar is 50% fructose sucrose, table sugar is half glucose, half have fructose. The fructose that we get packaged with fiber and vitamin C, which aids in uric acid excretion in the form of fruit is great. You know, eat an apple a day, eat a couple of apples a day. Wonderful. Now, you don't want to spend your whole day eating berries like a bear, but some fruit on the table is great. Purine rich vegetables, cruciferous vegetables have a lot of purines. Eat them all day long, it's totally fine. There's great fiber. There are bioflavanols that actually inhibit the most important enzyme for uric acid formation, xanthine oxidase. So things like quercetin and luteolin are powerful in terms of reducing the body's uric acid. One study done in England looked at, I think, 22 young men with mild elevation of their uric acid. Put them on 500 milligrams of quercetin a day. And after eight weeks, their average uric acid level declined by about 8% Quercetin Health Food Store item. And guess what? In addition to reducing uric acid, quercetin amplifies ampk. That's what we want. That helps us lose weight, it helps control our blood sugar, it helps control our appetite. Another way to activate AMPK is exercise. Who knew?

And exercise increases the bdnf, the brain derived neutropenic factor also, right?

So you bet. And you know what? You can do something. You know, I exercise a lot and I get injured probably as much as anybody else. You know, there are days when I can't run because my knee hurts. But then you walk or you use the elliptical machine or do a bunch of sit ups or something. You could always. In my opinion, there's something that you can do if you're confined to a wheelchair. You can do curls with dumbbells. There's something. Or use a band. There's something that everybody, probably most everybody, can do each and every day to get their heart rate up and to stress their muscles.

Make some small improvement today that you didn't have yesterday.

Yes. And interestingly, when you do that, and therefore in a very minimal way reduce inflammation in your body, you're enhancing the likelihood that you're going to make a better decision tomorrow. It has to do with our ability to make these good decisions, to eat right, to get sleep, to exercise, spend time in nature, et cetera. And our decision making is really dictated by a balance between, let's say, two brain areas. A primitive I want it right now, I don't care about tomorrow, I want it for me, everyone else be damned. Area of the brain. The child in the room, if you will, called the amygdala. And then the adult in the room called the prefrontal cortex. And the adults in the room saying, hey, this may not be good for me. How might my actions affect other people? How will this play out tomorrow or 10 years from now? You know, and that gets back to our conversation about making these choices because of the long game. That's the prefrontal cortex talking. We want the adult in the room to rein in the amygdala, to say, yeah, I know you want to eat that. Or say, I'm watching TV all day or playing video games, but that's not really what we're going to do. That's the adult controlling the child. That's the prefrontal cortex connected to the amygdala and calming it down. But we deeply depend on that connection. So that pathway, that phone line that lets the adult talk to the child and make better decisions is threatened by inflammation. Think about that, that connection, that ability of our prefrontal cortex to do all those great things, make better decisions for the long game is threatened by inflammation. It's the reason when you're up all night and your body's inflamed, you eat crap that next morning. We've all been there. I mean, I remember in residency it was baby food from the pediatrics ward, it was sugar. But it's the reason we don't make good decisions when our bodies are inflamed. It's why even mild overweight becomes obesity. Because you can't stop, you make worse decisions, you end up being sedentary and parked in front of the TV all day long. The goal is to break that vicious downward spiral in some way. And maybe it's a little bit of exercise today, maybe it's turning off your television and any other screen devices after 6pm and trying to get a better night's sleep. Not having caffeine after 2pm Maybe it's reconnecting with nature. Or maybe you start off with the dietary changes. Who knew, who knows? But any way that we can insinuate into that feed forward downward spiral to break it can be on ramps for better decision making and therefore better health.

What do you do for people whose frontal cortex, prefrontal cortex aren't developed yet because of their age? Were you going to ask that?

I mean, because decisions, it's not developed, it's very challenging. I mean that's. And it's really this prefrontal cortex gaining control that defines being able to make adult decisions. It's why you have to be a certain age to drive a car, to vote to serve in the military, et cetera. But truly, with so many people, even into adulthood, they've taken their prefrontal cortex offline and are making impulsive, self centered, narcissistic decisions day in and day out. And it doesn't serve them and it doesn't serve others and it doesn't serve the planet.

I just find that, I mean, thank you for that connection because that actually gave me a lot of insight. One of the interventions I recommend is doing if somebody needs a reset, a great reset is just a fast. And I know for myself if I'm fasting three to five days, I'm going to eat very differently afterwards than I did before. And that's sometimes actually I know, as if I'm going down the wrong path. Like I can see I can't control, sometimes I literally can't control the food Because I just want it. If I do some kind of reset, it changes. So that gave me. Thank you. Because that gave me the insight to understand why, which is really cool.

Well, and I'll say from my perspective, fasting, the main, the most important thing that it amplifies in me is gratitude. You know, you're grateful to have food afterwards. But all types of gratitude that I think about during fasting are amplified. Family, friends, you know, the world, all the things that we need to be grateful for. And you know, some people get to those places with hallucinogens through meditation, through, you know, aggressive exercise. They put themselves in own and. But I think fasting is a very, very handy way of doing it, you know, aside from, you know, the other health benefits that we could talk about.

Yeah, no, it's, it's. I, I thank you for bringing up the gratitude because it's just makes time slow down and gives you time to reflect and. Yeah, it's, it's so important in this world where we're just going a thousand miles an hour and trying to do whatever we do. And even the people that are exercising so much, sometimes it becomes routine. So breaking a cycle and just pausing, you bet.

Is there anything we didn't ask you that we should ask you? You want to make sure you say before, as we're drawing to a close, there's tons to talk about.

Yeah, I'm like, I don't want to stop, but it is our time.

Let me just maybe make more mention about the uric acid connection. So just so people can again. So uric acid is playing a role in our metabolic health. We want to keep our uric acid level at 5.5 milligrams per deciliter or lower. For anyone who's watching this from another country, various countries have various units, so the numbers may be different. That the biggest player as it relates to elevation of uric acid in our modern world is our consumption of fructose sugar. That half of table sugar is fructose sugar. That alcohol and organ meats contribute as well. The worst offender in the alcohol world is beer. Beer is high in purines from the brewer's yeast, but also has alcohol. And the best choice would be probably wine. And that with greatest respect, many of your viewers, healthcare providers may not understand uric acid aside from the context of having gout. It's the new kid on the block. I recognize that. But I'm very buoyed to see the number of research studies coming out that talk about uric acid control as it relates to metabolic health and the number of doctors and healthcare providers who are talking about it now in their podcast, their forums, their online, their postings, et cetera. So it's really starting to gain traction now. And it's not going to be the end all, but it becomes another tool in the toolbox. And it's something that people can easily made aware of. It's something you could test at home, just like you could test your blood sugar. So, you know, those are the key points on uric acid.

No.

Appreciate it.

Awesome.

Where can people find you?

Yes.

DrPerlMutter.com is my website. DrPerlMutter.Com that's probably the best place to start. That then segues to Instagram and Facebook. And the Empowering Neurologist is my podcast, the Empowering Neurologist. And I have a great time interviewing smart people like you guys and getting information out. People write books, we talk about their books. So I have a lot of fun with that. So that's where I am.

Awesome. Do you want to close it out?

Nope, it's all you. I do want to say that for our viewers that we, I have been following you for a long time and a lot of what we do is so based on your research and based on your knowledge. So I just really want to. Talking about grateful, extremely grateful for what you've done for me personally, for my patients and just the world. And it's, it's just been a pleasure and thank you for the privilege of interviewing you.

Well, that, that statement makes it all worthwhile for me, so I appreciate that as well.

Thank you for joining us for another episode of the Five Journeys podcast, Live like youe Matter. Our guest today was Dr. David Perlmutter. Thank you for being here.

My pleasure.

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