Ep. 193 – A Deep Dive into the Role of Uric Acid and Metabolic Dysfunction

Today I have the honor of reconnecting with Dr. David Perlmutter. Dr. Perlmutter is a Board-Certified Neurologist and five-time New York Times bestselling author. He joined me once before on episode 141: Reclaim your Brain, and we spoke about his book, Brainwash. He is with me today to talk about his newest book, Drop Acid, which focuses on the role of uric acid, fructose, metabolism, and metabolic health. 

In the wonderful work he does, Dr. Perlmutter brings to light how our diets profoundly impact our metabolic health and metabolic markers and talks about the many changes we can make regarding our food choices and the supplements we use. In this episode, we have a mind-blowing conversation! Dr. Perlmutter dives into how our bodies process uric acid, the impact of alcohol and fructose consumption, and how our metabolic health is worsening due to our current dietary choices. We talk about how high fructose corn syrup impairs insulin and leptin production signaling which translates into no satiety. We discuss the impact of metabolic health on brain function, resulting in one in every ten people older than sixty-five having Alzheimer’s. We also explain how obesity impacts cognitive and behavioral health and talk about how we can prevent all of those problems.

In my sixteen years of working in cardiology, I only ever thought about uric acid when prescribing medications that might give rise to gout flare-ups. Now, looking at things through this new lens, I see a whole world of opportunity to support people in new and different ways! I hope you gain a lot from today’s conversation and enjoy it as much as I did!

“Our bad lifestyle choices have come home to roost and are threatening our ability to live a long and healthy life.”

Dr. David Perlmutter

IN THIS EPISODE YOU WILL LEARN:

• Dr. Perlmutter gives examples of illnesses in the group of chronic degenerative diseases that the World Health Organization tells us are the number one cause of death on our planet. He highlights the importance of identifying their causes.
• The role of uric acid in human survival.
• Dr. Perlmutter shares some frightening statistics regarding the health of American adults and children and explains how bad lifestyle choices are threatening our ability to live a long and healthy life. 
• What is uric acid, where does it come from, and how are we getting it into our diets? 
• When we gain control of uric acid and combine it with healthy lifestyle choices, it can become a powerful tool, influence us positively, and help us regain and maintain our health.
• The difference between high fructose corn syrup and fructose in fruit.
• What does uric acid do in the body?
• The impact of fructose and uric acid on the brain.
• Why do high levels of salt consumption relate to obesity, type 2 diabetes, and hypertension?
• What does uric acid do that is threatening to our physical health?
• The fundamental importance of following a plant-based diet.
• Doctors can use a tape measure to measure people’s risk of developing dementia.
• Why do c-section babies have an increased risk of developing metabolic issues?
• Dr. Perlmutter talks about his LUV (Lower Uric Values) program, designed to help people reduce their uric acid levels.

Bio:

Dr. Perlmutter received his M.D. degree from the University of Miami School of Medicine, where he was awarded the Leonard G. Rowntree Research Award. He serves as a member of the Editorial Board for the Journal of Alzheimer’s Disease and has published extensively in peer-reviewed scientific journals, including Archives of Neurology, Neurosurgery, and The Journal of Applied Nutrition. In addition, he is also a frequent lecturer at symposia sponsored by institutions such as the World Bank and IMF, Columbia University, Scripps Institute, New York University, and Harvard University, and serves as an Associate Professor at the University of Miami Miller School of Medicine. He also serves on the Board of Directors and is a Fellow of the American College of Nutrition.

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Transcript:

Presenter: This is Everyday Wellness, a podcast dedicated to helping you achieve your health, and wellness goals, and provide practical strategies that you can use in your real life. And now, here’s your host, Nurse Practitioner Cynthia Thurlow.

Cynthia: Today, I had the distinct honor to connect again with Dr. David Perlmutter. If you recall, we recorded together on Episode 141 Reclaim Your Brain talking about at that time his most recent book, Brain Wash. Today, he joined me again to dive deep into his newest book, which I think is my favorite of all. It’s called Drop Acid and it really focuses in on the role of uric acid, fructose metabolism, and metabolic health. For those that are not aware, he’s a board-certified neurologist and five times New York Times bestselling author. My conversation with him today was just mind blowing.

The whole explanation around how our body processes uric acid, the impact of alcohol and fructose consumption, how the role of metabolic health is worsening given our current dietary choices, how things like high fructose corn syrup actually impair the production of insulin and leptin signaling, which translates into no satiety, therefore we keep eating, the impact of metabolic health on brain function, how one in 10 older than 65 years old now have Alzheimer’s, the net impact of obesity on cognitive and behavioral health and the things we can do. The wonderful thing about Dr. Perlmutter’s work is that, there are a lot of things we can change about the foods we choose to eat, the supplements we consume, and our diets that have profound net impact on metabolic markers as well as metabolic health. I hope you enjoy this conversation as much as I did.

I’d really like to start the conversation focused on the scope of the metabolic health problem that we’re looking at and then dive into the discussion on uric acid, because I think certainly, my platform talks a great deal about the impact of chronic disease states, and metabolic inflexibility, and it’s certainly not getting better right now, and so, I would love for listeners to hear from you, what is the scope of the problem that we’re dealing with right now and how does uric acid fit into that? Because for me and I was saying, we want to evolve shift and change as clinicians, and for me working in cardiology for 16 years, prescribing a lot of medications that provoked gouty episodes, that was as much as I thought about uric acid. But now, looking through this new lens, I feel it’s a whole new world and a whole new opportunity to support patients in very different ways.

David: Cynthia, I think that you hit upon the gold ring here, and that is that any of us involved in healthcare really have to focus on this overriding role that our metabolic disturbances are playing in terms of paving the way for our most dreaded and pervasive conditions. The World Health Organization is telling us that the number one cause of death on our planet is not some virus. It is a group of conditions called chronic degenerative diseases like coronary artery disease, type 2 diabetes, Alzheimer’s, even some forms of cancer. These are all underlying by disturbances of our metabolism, meaning insulin resistance, elevated reduction of body fat, locking up our body fat, so that we can’t use it, elevated blood pressure, these are metabolic disturbances. In a very real sense, when we look at these, we say, “Oh, those are all bad things. Why on earth would you ever consider it otherwise?”

In reality, for most of our time on this planet, it was powerfully helpful to be insulin resistant, and to have higher blood pressure, and to make more body fat, because they would serve as advantages for us when we couldn’t find food and we couldn’t find water. It’s really in the context of our modern world that we then see that these are paving the way for basically disaster, again, the number one cause of death on our planet right now. We have to then do our very best to identify what’s causing these problems. We’ve known for example that the sugar fructose has been associated with metabolic disturbances. The first really solid paper that came out was in The Lancet way back in 1970. I would have been in the 10th grade and it said, “Yeah, fructose sugar challenges our metabolism.” But we never fully understood how it happens until very recently, when all of the steps relating fructose consumption fell into place. We realized that directly it’s threatening our metabolism, but also, amplified through the production of something called uric acid, which is the end product of fructose metabolism. It lights up our bodies to prepare for winter, basically. It’s a powerful signal, this uric acid, telling us that winter’s coming, make fat, store fat, raise the blood sugar, raise the blood pressure. We don’t need that. That’s for darn sure. But our bodies want to do that, because our bodies want to protect us, so that we can survive.

Throughout our history, this was powerfully effective in allowing us to survive. The fact that we as humans and other primates have far greater uric acid levels than other mammals, for example, allowing our survival advantage. This set of mutations took place about 14 to 17 million years ago, when a series of genetic mutations over more than a million years caused us to lose the ability to make an enzyme called uricase, which would otherwise have broken down uric acid. We lost that enzyme. Our uric acid levels are elevated and that was an advantage. What I’m saying is that there’s this mismatch then between our genome and our influences on our physiology. In other words, evolutionary environmental mismatch, or where nature and nurture buttheads. I’ve been interested in this whole concept for quite some time. I published my first paper on this topic 50 years ago, half a century ago when I was 16, and I concluded that paper which is in the new book by asking the simple question, “What about those of us who are alive today, but we’re living with this outdated machinery?” In other words, we all have machinery that’s geared to keep us alive. We can’t find food, we can’t find water. It works pretty darn well. We have thrifty genes that make the most out of whatever we can find.

Well, today winter’s not coming. It’s not around the corner that we’re not going to have food. We’re targeting this pathway every single day by telling it to prepare us for food scarcity and it’s doing that. When you look around here in America, one-third, one in three adults isn’t just overweight, but actually obese by BMI measurement. In the distant future in the year 2030, that’s way off in the future, right? that number is going to be 50% of adults, eight years from now are going to be obese, not just overweight, half, one, and two. You see it happening. If you’re at an airport, you look at everybody, you’re seeing it happen that 83 million Americans are prediabetic and about 34 million Americans are already diabetic. That is devastating. When we think of what are the downstream consequences of being diabetic in terms of the brain, for example, in terms of kidney function, in terms of all the things that we know are associated with type 2 diabetes. When we see that 10% of kids between the age of 12 and 18 have been diagnosed with high blood pressure caramba. it takes your breath away. It’s not that we’ve suddenly developed a suite of genetic mutations that are leading to these problems, not at all. It’s the signaling that we’re giving to our physiology that’s playing upon these adaptive genetics, that’s leading to these maladies that are crippling us.

Again, the number one cause of death on our planet, our longevity began to decline two years ago prior to COVID. Now, there’s about a two-year reduction in longevity rates for adults in America. Ascribing that to COVID, it began before COVID. We reached our peak, we were doing pretty well, but now, finally, our bad lifestyle choices have come home to roost, and are threatening our ability to even live a long and healthy life. That’s what’s so exciting about uric acid. Is it the end all? No, it is not. But it becomes yet another powerful tool in our toolboxes to influence in a positive way when we gained control over uric acid. That’s something Cynthia that we’ll talk about. But it becomes yet another powerful tool along with exercise and getting a good night’s sleep, for example, minimizing our stress, getting out in nature, all of the things that you’ve been talking about for an awful long time that we can bring to bear to regain our health and then maintain our health. Really, I would say at the end of the day, but at the beginning of the day, that’s what it’s all about.

Cynthia: Well, I’m so grateful that you’re bringing this to light. For anyone that’s listening, you did a beautiful job explaining the full scope of what’s going on. It’s not just adults, it’s impacting our young people, our youth, even children, small children are being impacted by metabolic disease. This is not a sign that we are heading in the right direction. Knowing that we have other metrics of which we can look at to talk about how we can include more lifestyle pieces that will lower our risk of becoming ill. So, what exactly is uric acid? I know that as clinicians we’re familiar with this terminology, but for listeners, if they’re trying to understand what exactly is uric acid, where does it come from and how are we getting it into our diets? Because I think that’s a really important point.

David: Sure. For purposes of the quiz, it’ll be really simple.

Cynthia: [laughs]

David: There’re only three things that when they are metabolized, the end product is uric acid. They are alcohol, a group of chemicals called purines, and I’ll define that in just a moment. But the big player is fructose. Our fructose consumption increased between 1970-1990, 1,000%. These things all play into forming this uric acid, which then sounds the alarm that winter’s coming, we’ve got to raise the blood pressure, make fat, store fat, and all the things really doing our best to try to avoid. That’s the simple answer. I guess, on the quiz, it’ll be A, B, C, or D, all of the above. But I think we can break this down a little bit and for example, alcohol, not all types of alcohol are necessarily going to be dramatic in terms of raising uric acid. Hard alcohol raises uric acid pretty substantially. Wine in men, moderate amounts of wine consumption are associated with pretty much no effect. In women, a little bit of wine is actually associated with a bit lower uric acid and that might be because of some of the polyphenols that wine contains.

The worst player in the alcohol world is beer. Beer is an issue because yes it contains the alcohol that becomes uric acid, but it also contains this other type of chemical that becomes uric acid as well. It’s called purines. Purines are the breakdown product of nucleotides that come from DNA and RNA. When foods have a lot of DNA and RNA, because they have a lot of cells, then they form lots of purines, and that is metabolized into uric acid. Beers made from brewer’s yeast, which is exquisitely high in these new purines, and therefore you get the double whammy. So, that’s telling our bodies because you’re making a lot of uric acid to make a lot of fat. Now, we understand where the beer belly is coming from, because you’re making this signal to make fat from two sources, the purines and the alcohol. It’s interesting because Japan has been way ahead of the United States in this understanding of the role of uric acid and metabolic issues to the extent that they now are marketing purine free beer. You’re still going to get the alcohol, but the purines have been removed. So, that would tend to make much less uric acid.

Cynthia: It’s really interesting, because having had the opportunity to treat gout for a long, long time, and really thinking thoughtfully about the role of fructose as an example. Because for me, I’ve been talking about high fructose corn syrup for a long period of time, but what it does physiologically in our bodies, and even worse, the high fructose corn syrup option, because I’m sure there are people listening, saying, “Wait a minute, there’s fructose in fruit,” and how does that differentiate from high fructose corn syrup? When I was reading your book, it just reminded me of how significantly different they are. Would you stick to this? I think this is really important. I know I talk a lot about food labels, and reading food labels, and high fructose corn syrup is a GMO subsidized product. It proliferates in the processed food industry based on what I’ve read with your work and with Dr. Johnson’s acknowledging how critically important it is to avoid liquid high fructose corn syrup in particular.

David: That’s right. I can’t tell you that I’ve been on a podcast where the question of fruit versus liquid fructose hasn’t come up. It’s a great question because the messaging here is that we’ve got to limit our fructose. What is fructose by definition? Fruit sugar. That’s where the name comes from. Ose means sugar. The question about fruit I think is a very good one. It turns out that fruit consumption in moderation is actually associated with lowering or a lowered uric acid level. The various explanations for that, you mentioned the liquid fructose that’s just bombarding your body, whether it’s a soda or it’s fruit juice, apple juice, orange juice whatever, you’re getting a massive slug of fructose to the extent that this overwhelms the liver, and all of the downstream issues related to fructose consumption then get lit up, because of this massive concentration of fructose that is delivered to the body. Not so when you consume fruit.

Number one, it turns out there’s not a whole heck of a lot of fructose in fruit. An apple might have five, maybe 10 grams of fructose and you don’t gobble down an apple. You eat it over time, that fructose is released much more slowly, because of the fiber that’s contained in the apple. But interestingly, there are a couple of other things going on here that are really, actually very positive as they relate to uric acid production. They include the fact that an apple and other fruits will contain vitamin C that helps us excrete uric acid. We’re adding a negative to the equation there. But also, bioflavonoids like quercetin for example, contained in fruits and vegetables, target an important enzyme that is needed to make uric acid. It’s called xanthine oxidase. Targeting xanthine oxidase with quercetin is a very powerful strategy that we talk about in the book for people who need to drop their uric acid. That enzyme, when it’s targeted, when it’s shutdown to some degree, that’s how the gout drugs work. That’s how allopurinol works. We’re quite familiar with the notion of targeting xanthine oxidase enzyme to reduce uric acid. We’ve known about that for a long time in the context of gout.

To be sure, that’s the gout connection to uric acid is what we were all trained in. But this is not your grandfather’s uric acid anymore. It’s such a broad net that is thrown as we begin to unravel what uric acid is doing in the body. Yeah, at very high levels, it can crystallize in the extracellular space and form painful crystals in your toe. That’s an issue we’ve known about for, it’s been described for a couple hundred years, but this is again, not your grandfather’s uric acid. There was a great article published in, I think, 2012 collaborative study with Turkish and Japanese researchers, and I won’t get into the paper, but the title says a lot. It was called Uric Acid in Metabolic Syndrome from innocent bystander to central player. What does that mean? It means that, yeah, we’ve seen elevation of uric acid in association with hypertension, and elevated blood sugar, insulin resistance, and certainly abnormal weight gain. We’ve seen those correlations for an awful long time. Certainly, the work was done beginning two decades ago, but beginning about a decade ago, we really started to see a shift in our understanding that, “Yeah, it’s elevated, but it’s actually playing a mechanistic role.” It’s leading to some degree. It’s playing a role in causing these problems. Now that we know it and we can help people understand how to lower this uric acid, how to monitor their uric acid, it becomes as I said earlier, a really empowering tool in your toolbox for reigning in your metabolism and opening the door to be healthier.

Cynthia: I think that’s such an important message to make sure that people feel that there are things they can do to be proactive, there are things they can do to monitor this. I think the old methodology was worried about uric acid or at least I did in cardiology, only when someone became symptomatic. A lot of the drugs that I would prescribe diuretics in particular, especially, for my heart failure patients for which I am sorry, beta blockers and medications like that that they needed, and then they would provoke this elevation of uric acid, and then we would then address that problem. In fact, one of my favorite patients from my years ago in Baltimore used to call the gout that he got his big toe gouch, and so that became this running joke that he knew that he was over-diuresed or had gotten too much diuretics when his gout would flare.

Now, one of the things that I think is really interesting about fructose, in terms of what it does in the brain, and how it’s so inflammatory is that, it actually impacts dopamine signaling in the brain, and can lead to compulsive eating and food addiction, and that was an angle I had not considered. It makes sense now retrospectively, but let’s talk a little bit about the impact of fructose on the brain, vis à visthe consumption of these foods that are high in purines.

David: Well, to really unpack this, and if I do it through the lens of history, I think it’ll make a lot of sense. The consumption of fructose in our ancestors, be the paleolithic ancestors, even before that long ago, millions of years ago in our primate ancestors, fructose would happen in the late summer, early fall when the very few sources of fructose were available and would finally ripen when the starch would turn into fructose. We would like those foods because they were sweet. This development of the so-called sweet tooth, actually, it’s not the tooth, it’s the brain. The desire for sweet and stimulating the very pathway that you’ve just described is something that’s been present for millions and millions of years. It’s present in all humans today, though, some people say, “I don’t have a sweet tooth.” Well, you choose not to eat sweets, because they’re not good for you. But it doesn’t mean you don’t like sweet. When I have to say no to the dessert, it’s not that I don’t want to eat the key lime pie. I would love to eat key lime pie, but it’s not good for me that my brainstem is saying, “Yes,” but my prefrontal cortex is saying, “Hold on, the adult is in the room. Make a better decision. You don’t want to mess up your blood sugar. You’re wearing a CGM. You’re going to have to be accountable for that.”

But these are hardwired into us that we have this desire to satisfy ourselves to have that dopamine sense of appreciation, the craving then for sweet. You would then understand how having fructose and consuming fructose would stimulate that pathway along with helping make us gain more body fat, along with raising our blood pressure. The incredible thing about the whole mechanism is that, it’s what we call a feed forward process. It amplifies itself through uric acid. When fructose is metabolized, the first enzyme is called fructokinase. That’s really important that fructokinase does its job if fructose is to be metabolized. At the end of the metabolism, we create uric acid that does what normally you would think it would then shut off fructokinase as a feedback mechanism. It stimulates fructokinase to keep it going. That is a powerful mechanism to prepare us for food scarcity. The desire to eat more food, the leptin resistance that we develop from consumption of fructose directly leads to the fact that our brain doesn’t tell us we should quit eating. That’s clearly related to fructose consumption and uric acid playing a role there as well. These are incredibly detailed survival mechanisms hardwired into our brains that gave us an advantage, that would say, once we started– and we all know it true. You start eating sweets, it’s hard to turn that off.

Once it starts happening, you need that second piece of key lime pie. Why do I keep saying that? Because I live in Florida. That was one of my favorite things, key lime pie and ginger ale. But we all know that once we start, it’s very difficult. Even to make it a little more complicated, but for me a little bit more exciting is the idea that our bodies actually make fructose. Who knew? We’ve talked for years about limiting your fructose consumption, especially, the fructose in beverages and the onslaught of fructose, what it does to our physiology, so you could be fructose free, and yet, within your body, and in your brain getting back to signaling, and this whole pathway of wanting to eat more. You can make fructose through what is called the polyol pathway, where we convert blood sugar or glucose into fructose. There are several triggers for that. One, that is extremely important is when the body thinks that it is dehydrated. How does the body know or believe that is dehydrated? Your sodium level goes up. It becomes more concentrated. At that point, a variety of mechanisms go into place. We stimulate various enzymes that allow us to retain water, because we know through activation or through the elevated sodium that we don’t have water, we’re becoming dehydrated, vasopressin helps us conserve water, and there you go.

But we also activate the formation of fructose de novo in the body. Who knew? Now, why would that be helpful, for example, for dehydrated? Well, because the downstream product of fructose ultimately is uric acid that tells the body to do what? Make fat. Well, why in the world would making fat be a survival mechanism if we can’t find water? Well, the example I like to use is the camel. When you see a camel, not that it’s something we see very often, but imagine then a camel that this animal is able to walk across the desert and not drink water. How does it do that? Well, what’s the unique identifying characteristic of the camel? It has a hump. Inside that hump, is not water. It’s fat. When you and I burn fat, we create two things, carbon dioxide and metabolic water. Storage of fat for our ancestors, for the camel, for the hummingbird, for the whale is a powerful reason source from which these animals are able to make metabolic water and not become dehydrated. That signal is high sodium.

Now, these days people are not becoming dehydrated, but guess what? We’re triggering the mechanism by eating too much salt. When you’re getting ready to watch the big game, and you’re parking yourself in front of the TV, and eating a bag of highly salted pretzels, your sodium level goes up. It isn’t a lot. It doesn’t need to go up a lot. These mechanisms are very sensitive. When that sodium level goes up, you trigger this long-standing mechanism in your physiology that’s been present for millions of years that says, “Oh, make fat because we need to make metabolic water, because our sodium level is up.” But we’ve tricked it, right? Well, now that you know that and you can’t control, you’re going to park yourself on the couch, and watch the game, and eat the pretzels. That’s what you want to do whatever you’re right. All you have to do is make sure to drink enough water with that sodium load, and you’ll dilute it down, and you won’t create as much fructose, and therefore, you’re not going to make as much fat. This explains an awful lot because we’ve known for decades that higher levels of salt consumption are related to obesity. They’re related to type 2 diabetes. My gosh, we’ve known at least for three to four decades that higher salt consumption is related to hypertension. But now, we know why? Because you’re triggering this ancient mechanism in your body, because your body thinks it’s dehydrated. Now, by simply understanding that, look at the tools that you have that can help you understand how uric acid is playing a role in telling your body to prepare for food scarcity, to prepare for water scarcity, and it just doesn’t have to happen.

Cynthia: It’s absolutely fascinating. Are we differentiating between processed iodized salt or even natural sources of salts?

David: Great question. There’s a lot of narrative about, “Well, I’m not having salt, I’m having Himalayan Sea salt that it comes from 2000-year-old, whatever,” and its salt, its sodium, and it’s going to raise your serum sodium level. I would say that if you’re going to eat salt, there’s some advantages to something like Himalayan Sea salt in terms of other things that it contains as well as its purity, and certainly, iodized salt, very common these days, a source of iodine that we all know we need if people are not eating other iodine rich foods, like shellfish for example. We have to look basically at the sodium content of the foods that we are consuming. That level continues to rise as do rates of obesity, hypertension, and diabetes. There’s a very powerful mechanism for that, that I’ve just described. The initiation of fructose production in the brain when this polyol pathway converting glucose into fructose is activated, downstream effect, uric acid is produced. One of the biggest things that uric acid does that is so threatening is, it compromises mitochondrial function, it increases free radical mediated or oxidative stress intracellularly and that damages mitochondrial function, which is what we do not need. That was a survival mechanism. It damages the Krebs cycle and the mitochondria aren’t going to use as much fuel to make ATP. So, that was a survival mechanism.

Nowadays, when we threatened [crosstalk] mitochondria, oh, my gosh, we’re doing a bad thing. We’re increasing our risk for Alzheimer’s, all kinds of mitochondrial related issues. The other important driver of this production of fructose within our bodies is higher levels of glucose. That is certainly pretty pervasive these days. When our blood sugar level is elevated, when the environment in the middle you for example, in the brain, when there are higher levels of glucose in the brain that pushes the production of fructose, so what we see in the Alzheimer’s brain is yes, higher levels of glucose, because it’s not being utilized, because insulin is not as effective, and then that higher level of glucose pushes the production of fructose and its precursor which happens to be sorbitol. It doesn’t go directly from glucose to fructose. It goes from glucose to sorbitol, then fructose.

One recent study demonstrated as much as a fivefold increase in the fructose level in the brains of Alzheimer’s patients, and also a dramatic increase in the sorbitol level in the brains of Alzheimer’s patients being brought on by the fact that their brains couldn’t utilize glucose, and therefore this excess glucose is floating around becomes fructose, uric acid is elevated, then the mitochondria are threatened. This whole bioenergetic theory of Alzheimer’s that has been talked about now for 15 years, I think now has legs to stand on, because now we get why the mitochondria are threatened. It all begins– It’s hard to say where it begins, we know that the mechanism looks like that step one may well be insulin resistance, then accumulation of glucose in the brain, then driving fructose production, uric acid production happens in the brain, and that’s a mitochondrial toxin. We don’t want that, because when the mitochondria in the brain are not functioning well, higher levels of oxidative stress, those mitochondria trigger those cells to undergo what is called apoptosis or preprogrammed cell death. We don’t want that for our very, very precious brain cells. These are pieces of the puzzle that we’ve been waiting for an awful long time.

Now, we have the corner pieces of our jigsaw puzzle, that’s big time. Well, next we’ll do of course the edges, and then fill in the middle, but those were important pieces. Because yeah, it’s great to understand biochemistry, but there is translational information in here for us all that, yeah, it’s important to understand, we don’t want to be eating a lot of fructose, we get that. We got to limit our sodium consumption. I think your viewers understand why. But it’s also the notion of doing our best not to become insulin resistant, because if we do our blood sugar, glucose goes up, and that will drive fructose production and uric acid production in our bodies, even though we’re trying to limit our fructose consumption. For me, it goes back to Grain Brain, where we’ve talked about refined carbs, and consuming sugars, and why that was threatening. But I admit, in 2013, when I wrote that book, this information was unavailable to me. We didn’t know this stuff. Then, we know it now and I don’t know what the future is going to hold. There’re still some pieces of the puzzle we want to figure out, but I think we definitely have the broad strokes.

You’ve been talking about them on your program, especially your most recent podcast that you’ve put up talking about why a plant-based diet, for example, is really fundamentally important. Because it’s limiting the provision of these refined carbs. It’s providing wonderful sources of fiber to nurture the gut bacteria that related to uric acid, maybe something we’ll talk about in a moment. But it really comes down to keeping that prefrontal cortex involved in decision making, making better choices based upon your knowledge base, and your role. My role as a doctor means teacher, and doctor doesn’t mean healer, it means teacher. I would say that your training in many ways is far more valuable as it relates to what we’re talking about. Then, with all due respect medical doctor training that I received and that is still happening in mainstream medical school. You’ve made a really good choice in terms of your career, because it paved the way for you to be in this position right now, which is so incredibly exciting, because I think now the public has come around to saying, “Hey, we get it. There are limitations of what modern medicine, interventional medicine can do.” That modern medicine is really focused on treating the smoke, but not the fire. That you’ve been emphasizing prevention and keeping us healthy for an awful long time.

Some of us in the MD world have been doing that, but wouldn’t it be great, wouldn’t it be really fantastic if there was more of an emphasis in medical school and in the practice of mainstream medicine that we realized what John Kennedy said, and that is that “the time to fix the roof is when the sun is shining.” It would keep people healthy. But we’re seeing it happen. We’re seeing so many people are becoming vociferous and really engaged in making this information available. Letting people know that, “Yeah your doctors can help you, but the ball is really in your court. If you want to stay healthy today, and not really be in a position where you’re hoping there is some treatment for your situation.” In my world as a neurologist, looking at the big player, which is Alzheimer’s disease, we don’t have a pharmaceutical fix for that issue, now, affecting 6 million Americans, and yet, we understand clearly that this is at its heart, a metabolic issue and we have the tools to control metabolism. When we see, for example, Japanese literature, one study published in 2016 that followed 1,600 individuals for 12 years. The beginning of the trial, they looked at their uric acid level. Then every two years during the trial, they did a neurocognitive test. Basically, how well is your brain functioning. What they found at its conclusion was that those individuals, who had the higher uric acid at the beginning of the trial had about an 80% increased risk for developing dementia. They had a rather a 50% increased risk for developing Alzheimer’s and a 166% increased risk of developing what’s called mixed dementia or vascular dementia in correlation with having a uric acid level of 7 milligrams per deciliter or greater.

Now, that opens the door to the notion of well, what’s our goal in terms of our levels. You and I both grew up with well, if your uric acid levels below seven, you’re in the normal range. I think we recognize, I know that you would indicate that we don’t need normal, we need optimal. That number seven milligrams per deciliter, which most doctors are going to say is, “Anything below that, you’re great. You’re good to go,” really relates to gout, doesn’t it? That figure was from where it was derived. Not only because above that level, people tend to have higher risk of having gouty flareups, but also above 7 milligrams per deciliter in the blood that’s when uric acid begins to precipitate out and form the crystals. But we want to strive for a level as it relates to our metabolic health of 5.5 milligrams per deciliter or lower. That’s above 5.5, we start getting into trouble as it relates to cardiometabolic issues, raising blood pressure, raising blood sugar, increasing our fat production. It’s a lot lower. That is why people need to understand their uric acid levels and that may be as simple as calling your doctor, because it’s generally included in your annual bloodwork and say, “BTW, what was my uric acid level when I was in the office six months ago or maybe I’ll go in and ask my doctor to check it” and he or she is going to say, “Well, you don’t have gout. What’s the big whoop?” That’s what we’re talking about today.

The other bit of good news is that you can go online, no prescription needed, and buy a uric acid monitor, and measure it at home. I have one, I have it right here. Oddly enough and here’s my most recent level 4.7. This is a device that works like a home glucose monitor. You do a tiny finger stick, you put on a strip, you put in machine and pressed out, you know your uric acid level. So, it’s within reach now. We can get our uric acid levels checked, and then we can modify our lifestyle immediately, bring it under control, and that’s going to go a long way to balancing our metabolism.

Cynthia: I think it’s so important to give patients opportunities to have some control over their lifestyle choices. I love that you wrap that in talking about the interrelationship between whether it’s with a continuous glucose monitor, and a uric acid monitor, and having conversations with their healthcare team about the direction they want to see things go. I want optimal levels, not lab value levels. I may not have gout, but I want to make sure that my uric acid levels are within a healthy range that I’m less likely to develop these metabolic diseases. I do want to go back to talking just a little bit about brain health, because some of the statistics in your book that I wrote down really blew my mind. In 2021, Alzheimer dementia’s cost the healthcare system $355 billion per year.

David: That’s B with the billion.

Cynthia: Billion. One in 10 greater than 65 years old has been diagnosed with Alzheimer’s. If you are obese between the ages of 40 and 45, it increases your risk of developing dementia by 74%. These are the bits of information and statistics that I want to share, certainly, during our discussion, because they’re takeaways, you have opportunities to turn things around, but if you are not optimizing your metabolic health, whether it’s with mitochondrial functioning, fasting, making better food choices, nutrient dense Whole Foods, avoiding a lot of the processed foods, the other piece that was mentioned in your book, high uric acid is an independent risk factor for cognitive deterioration, so, all of these pieces all come together. Certainly, as a neurologist through your lens, you’re seeing it from a very unique perspective, but one that all of us makes it incredibly reliable.

David: That’s right. Again, we don’t have a pharmaceutical fix for what you’re talking about. I wish we did. I’m not against if there were a drug, would I have used it in my practice who were available to me? Absolutely, I would have. Would have given my own father who died of Alzheimer’s disease that drug? Absolutely, if it were safe and effective. We don’t have that we watched what happened last year with the launch of– and the FDA approval of Aduhelm that now, we’ve seen how that’s played out that even Medicare is not going to be covering it. That’s pretty stringent, I think. It’s a pretty big signal that why that shouldn’t have happened. I think the FDA said, “Well, we don’t have anything that really works. We’ve got to do something.” I understand that, but primum non nocere, above all, do no harm. When we see this dramatic increase risk of strokes, bleeding strokes in the brains of the Aduhelm patients, those who received it, that’s not above all, do no harm. That’s not attention to primum non nocere, that’s doing harm. We don’t know the long-term consequences of these micro bleeds in the brains that are seen on the scans in follow up on people receiving that drug. We’ll leave it at that because our mission is to keep people from getting there in the first place.

The relationship that you’ve mentioned of metabolic issues to risk for Alzheimer’s is profound. Again, we talked about it back in 2013, the New England Journal of Medicine publication in September, I think of 2013 that talked about even a blood sugar of 105 is associated with a significant increase of dementia. Did I mention that there’s no treatment for that problem once it develops? We’ve known about this for a long time. Being a type 2 diabetic may as much as increase your risk by four-fold for a situation for which there that I mentioned, there is no treatment. You mentioned BMI and I’ve been asked, what are the most powerful tools for predicting Alzheimer’s? I have said that one of the most sophisticated tools that you can use in your office or laboratory is called a tape measure. Put the tape measure on somebody’s waist, and right away you know what is their risk and are they increasing their risk?

An interesting study came out last week that looked at multiple comorbidities. In other words, if you have two or more things going on in the metabolic world, like, elevated blood sugar, they looked at quite a few things, even depression, etc. If you have two or more, your risk for developing Alzheimer’s may go up as much as six-fold. But the important thing about the study, I think was a French study, the takeaway for me was that it was more predictive in people who were younger. Normally, you think, “Well, these are going to have real relevance in older people.” But it was more predictive down the line during the 32-year follow up, that’s a long study, of the people who had these multiple metabolic issues when they were younger. This is not the first time that we’ve seen this evidence. We’ve known, for example, that when you measure what’s called an Inflammatory composite Index in the old days, that was fibrinogen, von Willebrand factor, and total white blood cell count. Now, we’d use other markers of inflammation, like C-reactive protein, TNF alpha, IL-6, IL-1B, whatever. But my point is, they measured markers of inflammation in people in their 40s and 50s, and followed them for 28 years.

Now, of course, no big surprise. What they found is that people about 30 years ago, who were already inflamed had a dramatic increased risk of being developing a full-blown Alzheimer’s. I’ve often been asked, “Well, when should we start the Alzheimer’s prevention program?” This data would clearly suggest that it should begin in our 30s and in our 40s. Is that the default answer for me? No. When I see as I mentioned earlier that 10% of kids between the ages of 12 and 18 are now diagnosed with hypertension, and that’s a powerful risk factor for Alzheimer’s, then we move that number to that level to adolescence. Is that when we should begin the Alzheimer’s prevention program? My answer, no. Because now we’re seeing soaring rates of obesity, overweight, and even insulin resistance, and diabetes in children. Maybe that’s when we should make the recommendation for the brain healthy Alzheimer’s prevention program? I say, no. I say it should begin in utero and even before conception. because we know that events going on in utero and the mode of delivery, whether it’s vaginal delivery, or cesarean section play fundamental roles in charting the health destiny of that kid, that child, that there’s a dramatic shift in how the immune system, for example, functions whether a child is developed by C-section or passes through the birth canal, and is anointed with specific bacteria to setup his or her microbiome that plays a major role in regulating inflammation throughout that child’s life and regulating immune function. Dramatic increased risk of autoimmune conditions like celiac, type 1 diabetes, and kids born by C-section who did not receive that anointment.

It’s a lot to cover. But I’m hoping that you and I right now are speaking to people who are younger, who are not necessarily until today thinking they were at risk for developing Alzheimer’s, developing coronary artery disease, developing type 2 diabetes, developing various forms of cancer like colon, breast, or pancreas that are clearly related to some degree, to issues related to metabolism. We’ve got to for many reasons check in on our lifestyle biometrics, on our parameters that are informing us as to our state of metabolic health. We’re now putting uric acid right up there with measuring your blood pressure, your fasting blood glucose, your BMI, it’s right up there in terms of a powerful marker of metabolic dysfunction, but also as a very, very highly leverageable tool in the toolbox to regain our metabolic health in and of itself that’s important. But when you bring up things like Alzheimer’s, it’s a tragic story. You quoted a very powerful statistic in terms of what we’re seeing now. You mentioned at age 65, the rates of Alzheimer’s in America at age 85 and above, the most rapidly growing segment age wise of our population is 50-50. That’s the flip of a coin. But you can influence whether it’s heads or tails based upon what we do today.

Cynthia: I think that’s really important that there is hope, and there are opportunities to change the direction that our life is going in. Now, I know in your most recent book, Drop Acid, which I indicated before we started recording was, I said I’ve read all of your books, but this is the one that I enjoyed the most, because it’s so- [crosstalk]

David: I was happy to hear that.

Cynthia: [giggles] -aligned with a lot of what we talk about on this podcast. Let listeners know a little bit about your LUV program, L-U-V, that is designed to help patients, clients reduce their uric acid levels, and do it in a way that is accessible and reasonable.

David: Sure. Right now, I’m thinking of Buddy Love from The Nutty Professor, one of my favorite movies of all time. Gosh, Eddie Murphy, unbelievable. Anyway, this is spelled L-U-V, and it’s an acronym for Lower Uric Values. It really is a way to look at lifestyle choices through the lens of uric acid. Most of which of course is nutritional. Our nutritional input powerfully signals our body as to what’s shaken, as to what’s going on, and more importantly what we can expect. When we suddenly load our bodies with fructose, for example, it mimics what our ancestors did when they were preparing for food scarcity. Eat a lot of fructose turns on the uric acid, make a lot of body fat. Most of what the program deals with is a nutritional and is looking at the kinds of foods we eat, but the unique thing is that you can use this program that we have articulated and look at it through the lens of paleo, keto, vegan, mostly plant-based, whatever is your desire for whatever reason, you can modify that program, maintain those concepts that you think are important for yourself. But in addition, adopt the fairly straightforward recommendations to target uric acid and lower it.

But step one is certainly knowing where you are, how aggressive do you need to be, is your uric acid really high where not just fructose, but you really have to completely eliminate purines or reduce them dramatically, and go off of alcohol completely? Who knows? You won’t know until you know your uric acid level, and not just what it is today, but how it plays out as you implement the various things we talk about. The diet is somewhat or significantly plant-based, and you’re hearing that from the author of Grain Brain. People thought, “Oh, it’s all about eating meat. It’s the Atkins diet all over again, in Grain Brain.” Never was. It always plant-based to a significant degree. That’s what I’m saying here. I am not saying that for people who eat meat, you shouldn’t. I eat fish, I eat chicken. I don’t eat organ meats, which are exceedingly high in purines and can raise uric acid. The reason I’ve never eaten organ meats is really quite simple. I never liked them. I never liked them since age 5 when my mother would cook liver and onions and I ran away from home. That’s how it is with me. Whatever.

Is there an upside to eating liver in terms of B12, in terms of iron? You bet. I get it. Should it be considered helpful? You bet. A lot of people eat organ meats, because there are upsides. But we’re talking about limitation of quantities of organ meats, of shellfish like scallops and mussels, of small fish like sardines and anchovies. I eat anchovies, and I eat sardines, and I showed you what my uric acid level is. It’s about knowing where you are, and what is the effect of these other foods that can influence a uric acid. I eat fruit, but you can be certain. I can say this direct to camera that I do not drink soda and I do not drink fruit juice. That’s for sure. That said, again, it really depends on the individual. So, that’s what the diet is all about. It’s about avoiding those foods that will clearly raise uric acid adding more plants to your regimen because we want to nurture the microbiome, we want a lot of bioflavonoids in the diet to target that enzyme to reduce uric acid formation. We’ve known that consumption of, for example, cruciferous vegetables, especially good, fresh, organic cruciferous vegetables is associated with a lower uric acid level. Beyond all the other things that we can argue in favor of why we’d want to eat them and there are sprouts, for example, broccoli sprouts. We could have the sulforaphane conversation. You’ve already had that. So, people can watch your other episodes.

But that said, again, other things to consider, we have what are called our hero ingredients. These are specific foods. We’ve talked about eating fruit. But eating tart cherry, that’s been associated with dropping uric acid for decades. Eating tart cherries or drinking tart cherry juice without added sugar has been recommended for gout sufferers for an awful long time. It’s the reason on the cover of the book, you may not have picked up on it, but you see the “Oh,” on the drop, “that’s a cherry falling” meaning connoting that it’s going to help your uric acid bubble fall. I didn’t design that. I did choose the name but that said. We have throughout the 40 recipes that we provide our hero ingredients, and they’re always called out fruits and to a lesser extent, vegetables have vitamin C, and vitamin C helps us with the excretion of uric acid. It does take us to a place of looking at a couple of nutritional supplements that can be helpful. Quercetin targets the same enzyme, xanthine oxidase that the gout drug targets allopurinol. That is, it reduces the activity of a fundamental enzyme for the formation of uric acid. That is this xanthine oxidase enzyme. Quercetin does it and it does it in a very handy way, as does another bioflavonoid called luteolin. Dosage of quercetin 500 milligrams a day, dosage of luteolin 100 milligrams per day, in addition, 500 milligrams of vitamin C will help with the excretion of uric acid. That’s a great place to get started.

Now, again, know your uric acid level, get a monitor or go to your doctor’s office, or call your doctor and say, “Hey, I’m heading to the lab. Can you call it in, fax them or email them a prescription? I want to know my uric acid level.” I would say to your listeners, be prepared for the question. Well, we spoke to the doctor and she or he is puzzled as to why you want to know this, because you don’t have gout. It’s going to happen. It’s going to happen an awful lot. That’s when you take a deep breath and just say, “I’m curious, or I’ve googled two things, uric and metabolic.” That’s all I would ask your viewers to google. Metabolic, not metabolism. Metabolic and uric, watch what comes up. You’ll get pages, the first three or four pages on Google of all the references that have been published over the past 20 years. Many of which by Dr. Johnson, that really demonstrate that not just is uric acid elevated in our metabolic issues, but that it’s playing a role in causing them. So, that would be step one. If your viewers want to be bold, they might just recommend to their doctors to do exactly the same thing. Google uric and metabolic, and see what comes up. We’re at the very beginning, that’s for sure. I would say we’re riding the crest of the wave, not yet. We’re still paddling out and waiting for that wave to come, then we’ll ride it in.

Cynthia: Well, thank you for this discussion today. As always, I’m a huge fan and I know this information will be hugely impactful for the listeners. Please let us know how to connect with you outside of the podcast, how to get your new book, which I’m so grateful to have a copy of and will be recommending as well.

David: Oh, my gosh, thank you. I’m available at drperlmutter.com. DR Perlmutter dotcom. The book is called Drop Acid, and the website is dropacidbook.com, and it’s available everywhere. We’re getting a lot of great feedback from people like yourself, and it makes me very, very happy. Now, as I mentioned at the beginning of our time together today, Cynthia, and that is the term ‘doctor,’ it doesn’t mean healer, it means teacher. You’ve certainly hit the ball out of the park when it comes to that. When I see the people that you’ve interviewed, and your incredible compassion and skill at letting the information come out, and carefully crafting the direction that it goes in, you’re really fulfilling your title of doctor and it’s a beautiful thing to watch.

Cynthia: Well, thank you so much. I look forward to our next conversation.

David: Me, too.

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