The SHOCKING SCIENCE On Preventing Obesity, Diabetes & CHRONIC DISEASE | David Perlmutter

Only 12% of American adults are metabolically healthy. You can talk about viruses all you want, but that's not what's killing most people on our planet.

So most of the time when we're eating fructose, it's in the form of fruit, right? Which you said is okay. It's in the form of high fructose corn syrup, which is different in structure than regular sugar. Both contain glucose and fructose, but they're different. Can you explain how they're different? and, and, and is table sugar as bad as high fructose corn syrup?

And I would say that, how do.

We think about that?

You know, most of the time when you say most of the time, you know, we get our fructose from eating fruit, actually, not now, not now, but we should be getting it. Very little of our fructose when we recognize that, you know, more than 60 of the foods in the grocery store that carry a barcode are sweetened. And by and large, that sweetener is a either directly high fructose corn syrup or derivative thereof, it means that there's an awful lot of fructose going into our diets to make us satisfy our desire for sweet and buy the product. I mean, you know, I'm speaking to the choir here. This is what you've been talking about for years. You know, hacking into a primitive survival mechanism that says, seek out sweet foods and you will survive. Well, now, you know, all the foods are sweet and they're making us sick. High fructose corn syrup is 55% fructose as opposed to table sugar or sucrose, which is a 50-50 mix between glucose, which is less sweet, and fructose, which is much sweeter. The reason that we use high fructose corn syrup, that's older technology, was actually University of Oklahoma in 1957 was when we first saw the development of the process to make high fructose corn syrup. It's basically because it's very sweet and it's really cheap. Hey, sign me up if I'm a food producer. I want some that's sweet. I can use most of it and it's cheap. So our bottom line goes way up.

That's right. That's why I asked if I asked the vice chair of Pepsi once and.

Why use high fructose corn syrup in your soybeans? Because the government makes it too cheap for us not to use it. Well, the government to this day sponsors corn production to the tune of $500 billion a year. I mean, so and where does a lot of that corn go? It goes to high fructose corn syrup to make us eat more sweet. and you know, the argument has been that fructose is not glucose, therefore it's a safer sugar because it's not going to, when you metabolize it, it doesn't.

Raise your blood sugar actually.

Yeah, that's the party line. It doesn't raise your blood sugar and doesn't require insulin for its metabolism, therefore it's safe. Well, immediately when you consume fructose, you turn on gluconeogenesis, you turn on the process to power your brain as a survival mechanism with higher levels of glucose, you also compromise insulin functionality right off the bat. So you are setting the stage for becoming a diabetic. It's been one study indicated a really large study, 42,000 men, 49,000 women determined that about a quarter of all the diabetes in the Western world is directly related to elevation of uric acid. Where do we get uric acid? Only from three sources, from alcohol, same metabolism as fructose, and from a class of chemicals that are called purines. Purines are the breakdown products of DNA and RNA, from foods that are rich in purines, things like organ meat and game. Organ meats game would be liver and kidney and how do you eat those? I don't know. but are you kidding?

I love chicken livers. My mom used to make chicken livers all the time for me.

Chicken livers and onions over rice. Really? I, I get that. I could never tolerate. I had, I ran away from home. Chop liver.

Come on.

What? But that said, by and large, that's not the issue. I mean, it's not necessarily the purine, you know, traditionally, because that was the old thinking, right?

Is it, don't eat meat, don't drink wine. That's what's causing gout. But nobody really talks about the sugar.

Aspect or the fructose aspect. But that's really the major driver. the issue. It's the fructose. It's not really, you know, two-thirds of the purines in your metabolism come from your own breakdown of your own muscle that you do whenever you exercise. And alcohol is certainly contributing to the uric acid pool. But the big elephant in the room is the uric acid derived directly from fructose metabolism, which is a molecule that.

Doctors often measure in the blood. We think it's associated with gout, but we don't pay much attention to it other than that. And yet it turns out it's a really important marker for many long standing metabolic issues that our population is suffering from. In fact, it's the biggest threat to our planet in 20, I think 20, 88% of Americans are metabolically unhealthy. That means they have some form of prediabetes, high blood sugar, high cholesterol, high blood pressure, and that's driving these host of chronic illnesses that are including obesity, diabetes, heart disease, Alzheimer's, so what's the deal with uric acid? Like, I I often measured. I've seen it high with people with insulin resistance and diabetes. And I thought it was a marker of some inflammation and some other issues, but I really didn't really treat it directly. I was always treating the underlying issue, which was the blood sugar and so forth. Unless someone had gout, then I'd give them a drug or cherry extract or something. But tell us what, why did you kind of hit on uric acid?

And what are the, what are the reasons it's so important? Boy, there's a lot of places to go, aren't there? How did I, I come upon this? I would say that, you know, as like you over the years, I've been really fixated on metabolic disorders. I'm a neurologist, and why would I be interested in diabetes and hypertension and obesity and dyslipidemia? Because they pave the way for certain neurologic problems that I then land in my lap for which at that point there is very little recourse. What are we gonna do? I mean, we all saw what happened in 2021 with respect to a new so-called Alzheimer's drug. We don't have anything. So if we can get to the root cause of some of these issues in neurology, you mentioned other things like diabetes and cancer and cardiovascular disease, we can understand the fire and not just focus on the smoke or the end product, then we have a leg up. We can keep people healthy as opposed to simply focusing on treating them. And so that sets the stage for me being open to understanding new developments in terms of what are the causes of these metabolic problems. And the truth of the matter is, this came to me one day while I was running. And typically when I run, I listen to either music or podcasts. I was listening to a podcast of an interview of a nephrologist from the University of Colorado by the name of Richard Johnson, who for the past two decades has focused on the role of fructose in metabolic issues and the primal mechanism of uric acid then in leading to these host of metabolic issues that the role of uric acid plays in elevating our blood pressure, in leading to gluconeogenesis, the new production of blood sugar, in making us insulin resistant, in increasing our production of body fat, in locking up our body fat so that we can't tap into it as an energy source. and we'll talk about that, how we as humans have this predisposition by virtue of our elevated uric acid. So you've known, we've all known for a long time that fructose is a bad player, right? We see correlations between fructose consumption and the very things that we're talking about, but we've never really understood, well, how in the heck does that happen? What's the link? and what Dr. Johnson was doing 20 years ago is he was creating hypertension, elevated blood pressure in laboratory animals by feeding them fructose. They would develop high blood pressure. And he noted that as a matter of fact, that their uric in doing a blood panel, looking at all kinds of things, that their uric acid levels would go up when he gave them fructose. Well, you would expect that. because unlike glucose, fructose is metabolized directly into uric acid. That's where it comes from, from fructose. There are two other sources we'll talk about. So he noted that, he said, well, isn't that interesting? Uric acid levels increased. Then he did something really fascinating. He gave them a lot of fructose, but he blocked the uric acid production by giving them a gout pill called allopurinol.

Yeah.

Lo and behold, here they're eating all this fructose and they're not getting high blood pressure because uric acid was not elevated.

Fascinating.

That is huge.

Fascinating.

And he determined then by repeating the study in men, the same thing happened. Give them a lot of fructose within a couple weeks, blood pressure goes up, weight goes up, insulin resistance increases, blood sugar goes up. But if you give them allopurinol and, you know, where you and I are going with this today is not to say everyone should take this drug. We'll talk about what you can do. But lo and behold, the same thing happened in humans. So that was groundbreaking. And at that point, you know, he began his research. But it's interesting to note that in 1894, Dr. Alexander Haig, a different Alexander Haig, wrote a book entitled Uric Acid, a Factor in the Causation of Disease. and looked at things like dementia and hypertension and depression and certainly rheumatism or joint problems and really discussed it way back then, but it remained buried until just about 20 years ago. Now, researchers around the world are looking at this and describing what to do. So, yes, it's a marker. You were correct in saying you notice that it's elevated, But there was an interesting report that came out of Turkey and Japan in 2016 that looked at uric acid elevation in metabolic syndrome as no longer being in the title, innocent bystander, but playing a central role. That it's actually mechanistically involved in causing these problems. It doesn't just happen to be elevated 'cause people have a crappy diet or they're not exercising, not sleeping well. It is the cause. A cause and important cause. Wow.

So, David, people are listening probably going, well, geez, does that mean I can't have an apple or is it just high fructose corn syrup that you get.

In soda and processed food? Like what's the deal? It's a great question. I can tell you it's something I'm asked every day. And here's what the literature tells us. And it's really quite interesting in that if you eat apple, if you eat five grams of fructose or two apples, 10, 15 grams of fructose, all well and good. An apple has quercetin, it has other bioflavonoids, it has fiber, fiber, which slows fructose absorption, and has vitamin C, which aids in uric acid excretion, as opposed to drinking a 12 ounce glass, 42 grams of fructose, you know, of orange juice or apple juice or certainly a soda. Those are the potent sources of fructose that we need to stay away from immediately tells your body something very important. That fructose signals your body that winter is coming. It's telling your body that caloric scarcity is coming. You might starve. You better make fat. You better turn on your production of glucose to power your brain. You better elevate your blood pressure because you're not going to have water to drink. It's setting the stage for survival. And this is a fascinating story that dates back about 15 million years. ago when the Earth cooled and there was some very powerful selective pressure on our primate ancestors for survival during times of food scarcity. And it turns out that around that time there was a mutation was actually a series of mutations in the genes that made an enzyme called uricase. Uricase breaks down uric acid and would lead to a lower uric acid level. But this mutation disrupted how uricase worked. So those who inherited this mutation had higher levels of uric acid. They made more fat, they survived. So we, as humans and other great apes, still have that mutation in uricase. So we have 4 to 5 times higher levels of uric acid than other non-primate mammals. these days, what we're experiencing is called an evolutionary environmental mismatch. So we're stuck with these outdated physiology that allowed our Paleolithic ancestors to survive, our hunter-gatherer forebears to survive when there wasn't any food. If they could stumble on some berries, a little bit of fructose, make a little bit more fat, didn't take a lot. Not that it made them fat, but just enough fat to hold them over till they could find food, you know, whether it was on the ground dead or they dug it up or whatever.

Well, David, I know you spent a lot of time on your boat up in Alaska, but, you know, the grizzly bears up there, they, they eat salmon in the early part of the summer, and they don't really gain much weight. Then they go up in the mountains and they eat all the berries, and they gain, like, 500 pounds from eating berries. That's right. And we, you know, what you're saying is really important because we have a lot of mechanisms that are adapted to starvation. People don't realize this, that we have hundreds of genes and mechanisms in our body that are really good at dealing with scarcity, but almost none that are dealing with abundance, because we've never had to deal with this before. We never lived in a food Carnival before. We never lived in food lalapalooza, you know, where there's everything all the time in abundance and the worst possible crap you can imagine. So our bodies don't know how to cope with it. And so this mechanism, which is actually designed to help us stay alive, is actually killing us now.

That's right. And again, we call it an evolutionary environmental mismatch. I wrote my first article on this in the Miami Herald in 1971 when I was 16.

Oh, wow. You're ahead of the game, huh, David?

I was, you know, it's crazy. I said, what, you know, what about us, the people of today who are sort of saddled with this outdated machinery. That was how I ended the article. Because evolution isn't going to save us. We're not going to be able to evolve quickly enough the mechanisms to deal with exactly what Mark, you've been writing about for years. And this is this horrendous assault upon our physiology by the very foods that are now global. You know, we used to talk about the American diet, the standard American diet, the Western diet. It's global now. face it. And, you know, we talked about in Brainwash how that threatens connections in the brain that make us less empathetic. But, you know, that's for another conversation we, you and I have already had with Austin. Well, that's a good podcast.

You should all listen to that podcast because they just to summarize it quickly, if I get this wrong, tell me. But essentially our modern diet, which is super inflammatory, disconnects our frontal lobe, which is the adult in the room from the limbic brain, which is the reptile, lizard, fight or flight, you know, reproduction feeding behavior, which is very triggerable. And so, all of a sudden, the grown-up in the room is not managing the intense emotions of this limbic part of our brain. And so, we act in ways that are destructive or violent or aggressive. And we see that in our society now as being a massively divided society, whether it's your paleo or your vegan or Republican or Democrat or Jewish or Palestinian or Muslim or Christian. It just goes on and on. And, and your argument is that part of that divisiveness could be related to what we're eating.

That's right. And, you know, what a match made in heaven that you and I are talking today because this has been in everything for so long. And, you know, for me, it's more about, well, what are the implications of that as it relates to behavior and the brain? And, and, and now we know that, you know, this uric acid, because of its elevation, threatens some really important physiology. As an example, it compromises the action of a chemical called nitric oxide. We need nitric oxide to do two very important things. It allows our blood vessels to relax, so we have good blood flow to our kidneys, our heart, and certainly to our brains. And in addition, nitric oxide and that effect of nitric oxide in blood vessels is what helps insulin do its job. Insulin requires nitric oxide to get out of the artery and also into the muscle cell to let it change glucose into glycogen and help keep our blood sugars under control. That is threatened by uric acid. And, you know, one other really interesting mechanism I think that you hinted about on when you were talking about the bears eating all the berries to get ready to hibernate is that that's a uric acid mediated event in them. They shift over between two very important pathways of metabolism. One is called AMP kinase and the other is called AMP deaminase. When we are stimulating AMP deaminase, we are favoring fat production. We are favoring locking up our fat. We are favoring the metabolic issues that we want to avoid. AMP kinase, on the other hand, which is not something that uric acid favors, is when we burn our fat, it keeps our blood sugars in check. Your insulin sensitivity goes up and, you know, basically that's what we do. We want to stimulate AMP kinase, why we exercise. It's why diabetics take metformin, is to stimulate this AMP kinase. That's exactly what's not happening when bears are getting ready to hibernate once they're hibernating and they're burning their fat, then AMP kinase is activated and it looks like uric acid is involved in that switch one way or the other. Where does the AMP come from? Very interesting. The AMP comes from the metabolism of fructose. When fructose is metabolized, it's an energy consuming event, unlike glucose. ATP is converted into AMP then where does the AMP go? We just talked about that. So it's totally a different kettle of fish, you know how fructose is metabolized. Fructose is the sugar of energy storage and glucose is the currency of energy utilization. And as different as night and day, you know, the real concern is that the metabolism of fructose into uric acid feeds back to cause more metabolism of fructose. It's a feed forward cycle. So uric acid stimulates the production of an enzyme called fructokinase, which is the first enzyme to break down fructose. So it just. It's self-perpetuating and what does that fructose do? It inhibits leptin sensitivity, so we eat more. It has.

Leptin is the hunger. The hunger suppressing hormone.

Right. And that's inhibited by our consumption of fructose. So we eat, and this was a great mechanism when to get ready for winter, you know, so we would eat more. That's why the Bears are doing what they're doing. They're preparing to hibernate. And if any of you, we just eat all winters. If any of your viewers are getting ready to hibernate, then have at it. You know, this, then that's for you. Eat a lot of fructose. But I think it's, you know, to get back to your original question that you and I talked about or learned about uric acid in the context of gout. If you had high uric acid, you might get gout, you might get kidney stones. But now we have a term that's called, it's pathetic, it's called asymptomatic hyperuricemia, which means you have elevated uric acid, but hey, you don't have gout, therefore it's not important. And asymptomatic hyperuricemia, it's clearly associated with hypertension, with obesity, with chronic kidney disease, and non-alcoholic fatty liver disease. One interesting study out of Japan looked at individuals with so-called asymptomatic hyperuricemia and found that they had significant increased risk for becoming overweight, for developing problems with their lipids, and even hypertension. You know, important components of the metabolic syndrome. And, you know, you started off with our discussion saying that 88% of American adults have at least one component of the metabolic syndrome. It means only 12% of American adults are metabolically healthy. And these are the big issues of our day. You know, you can talk about viruses all you want. Sure, that's important, but that's not what's killing most people on our planet. What's killing most people right now are the chronic degenerative conditions. coronary artery disease, Alzheimer's, cancer, diabetes.

These are metabolic issues.

Almost 50 million deaths a year.

Yeah, and related to the- 50 million.

Deaths a year, mostly. With an M, that's right. Yeah.

And, David, I just want to sort of loop back a little bit because I want people to understand what this fructose thing is. So basically we're getting it from high fructose corn syrup, which you said is 55% fructose, but it's actually, in some studies I've seen up to 75% fructose. That's right. And also it's important for people to understand that in traditional sugar, Fructose and glucose are bound together with a chemical bond. So they take some metabolism and they don't, they're not as quickly absorbed. Fructose in high fructose corn syrup is free fructose. And the other thing that you didn't quite mention, I'd love to hear your opinion about this, is work from Bruce Ames where fructose requires energy to be absorbed as opposed to sugar, which has a transport channel that doesn't require the use of energy. And when you use that energy for fructose and you're having mostly fructose as your sugar, It's causing depletion of ATP in your gut, which then causes the tight junctions, which are the things that prevent you from having a leaky gut to keep your cells stuck together like Legos. It causes those to separate, and then you get leaky gut, which then even exacerbates the problem of obesity and insulin resistance and diabetes through another mechanism, which is endotoxemia from the metabolic byproducts of bacteria and weird things in the gut. So it may be that fructose is causing problems with many, many reasons. partly obviously these metabolic effects, but also the gut effects which exacerbate the metabolic effects.

That's right. And again, this is all amplified by then the metabolism, which is an energy dependent event, ATP to AMP, then to uric acid. And that uric acid then enhances in the gut more pro-inflammatory bacteria, also dramatically increases the gut permeability, therefore increases inflammation. And how interesting it is that one disease that is associated with elevated uric acid, which is gout, has actually been demonstrated to be significantly improved in people undergoing what's called a fecal microbial transplant, where healthy fecal material is taken from an individual and then put into the colon of a person with gout, remarkable reduction in the number of gout attacks without any significant dietary change. So amazing. true. So, you know, the, we're back to talking about the gut, you know, a place where you and I default to over the years, and rightfully so. But, so uric acid itself is having such a dramatic effect on, on the gut.

Just on the microbiome itself.

You bet. Enhances inflammation. So if, if we recognize that inflammation is certainly a centerpiece of the damage done by uric acid, then all of the downstream issues related to inflammation might well be anticipated to be increased in people with high uric acid levels. And in fact, that's what we see in a 2018 study looking at 42,000, I think I mentioned earlier, 42,000 men and 49,000 women and followed these individuals over an eight-year period of time. What did they find? They found that all-cause mortality was dramatically increased in those individuals with high levels of uric acid. that those who had high uric acid had a significant increased risk of cardiovascular related mortality of close to 40% and about a 35% increased risk of stroke related mortality. This is a big study. I mean, we're talking about 100,000 people followed over eight years, having a 35 to 40% increased risk of death from either a heart attack or stroke, Here's something else that the study found I think was really interesting. That is, for every point elevation of uric acid above 7 milligrams per deciliter, for every point there is an 8 to 13% increased risk of all-cause mortality. So, this is mortality when we look at the cardiovascular, we look at the stroke, this is mortality related to issues that have inflammation as their cornerstone. So it's very important that we consider this, that we consider that uric acid is not just happens to be elevated, that it's playing a mechanistic causal role, and that we should do what we can to check our uric acid levels. You can use a home monitor. I'm gonna send you one. Or, you know, people get their annual blood work. Uric acid is almost always on the annual blood work. What is it? And for your viewers, the place where it needs to be is at or below 5.5, the units are milligrams per deciliter here in America. Typically, the lab will call it out if it's at seven or higher because that's the level that it starts to become an issue as it relates to gout and kidney stones. But as it relates to the metabolic issues that we're talking about, the increased blood sugar, the hypertension, the risk for all the things that we're talking about, we want it at 5.5 or lower. again, you can go online, go to Amazon, buy a uric acid monitor and check your level. I recently checked mine again and it's 4.6, so I'm feeling good about that.

That's good. So basically this uric acid phenomenon is really not well understood by most physicians. It's really driven by diet, but normally our processed diet and high fructose corn syrup and it drives all these secondary effects of cardiovascular disease, death, alzheimer's, cancer, diabetes, and it's something that you can actually easily measure. Your doctor can check it for you when you go to the office. It should be less than five and a half, as you said. What should we do in terms of our diet to reduce uric acid? And what are the worst things that cause uric acid and what actually helps reduce uric acid?

Sure. Let's talk about the causes or the sources of uric acid. Where is it coming from? Did we mention fructose?

Yes, you did.

Fructose is the gorilla in the room, right? So, fructose again was our signal that scarcity was coming, that winter is coming, eat the berries. Fructose is telling your body, make fat, raise blood sugar, raise blood pressure because you might not have water to drink. So, fructose is by and large the biggest player. Fruit juice, sodas, added the sauces. added to just about anything that's in a package these days.

Salad dressing.

You bet. And we love it because it's- Tomato sauce. And again, fruit is okay. An apple a day keeps the doctor away. Not apples and cherries and, you know, high fructose fruits all day long, but have some fruit by all means. The next thing to consider that's certainly less important are something called purines. Purines all fruits, vegetables and meats, really anything we eat has in it some DNA and RNA. When our bodies break that down, then purines are formed and purines are directly metabolized into uric acid. And interestingly, uric acid favors that and enhances the production of purines in our bodies. Again, a feed forward cycle. It's trying to keep us alive during times of food scarcity. So again, we want to avoid those foods that are really rich in purines. I mentioned them already, the organ meats, the shellfish, the smaller fish that we were favoring over time, the anchovies and the sardines. Sure, you can have the anchovies in your, in your Caesar salad, but you don't want to make big meals having six ounces or more of, of any of those. Oh, I love anchovies. Yeah, me too. White anchovies, one of my favorites. And the last thing to consider, I think it's needs a little bit of we need to double click on this a bit, and that is alcohol, because alcohol shares the exact same metabolic pathway as fructose, as Robert Lustig has called it. Fructose is alcohol without the buzz. So it similarly consumes ATP down to AMP. But in this case, it really matters what kind of alcohol a person is drinking. Wine consumption in men, Men has about zero effect on uric acid. Wine consumption in women actually is associated with lower uric acid. Hard liquor will raise uric acid, but the worst offender is beer. Why? Because beer not only contains alcohol, but it contains purines that we just talked about from the yeast, the brewer's yeast that is used to make beer. So now we understand the biochemistry that underlies the beer belly. It's coming from this elevation of uric acid packing the fat away, getting ready for winter. So if you're gonna choose a beverage, coffee, a good choice, actually associated with lower uric acid. So those are the big things that we should avoid. I will make one other comment as it relates to high-purine foods. Many people will pull up a list of high-purine foods and see many vegetables, things like broccoli, the cruciferous vegetables in general, like kale, many vegetables have high levels of purines. Their consumption, though, is associated with lower uric acid. Why? Because, again, fiber, bioflavonoids, vitamin C, which increases uric acid excretion. So eat, eat all the vegetables like that that you want. There's, you'll never hear, I don't, never say never, but it's going to be hard for me to imagine there'll be, there'll be a time when I tell people not to eat broccoli or broccoli. Exactly. Right. That's, that's gonna be a tough, a tough one for me.

So what are the foods help bring it down. Because if it's elevated, you can stop eating the purine foods and the sugar foods and the high fructose corn syrup foods. What are the.

Foods that are rich in certain bioflavonoids? For example, quercetin is a very powerful bioflavonoid. Yes, it's an antioxidant. Yes, it has anti-inflammatory activity. But here's the exciting news about quercetin. A recent study out of Britain demonstrates that 500 milligrams of quercetin a day in just two weeks is associated with an 8% lowering of uric acid. That's really significant. So taking quercetin as a supplement is an idea along with vitamin C. Luteolin also dramatically lowers uric acid on par with allopurinol, which is a pharmaceutical. one to one, just about equal to the drug used for gout patients to lower their uric acid. So luteolin and quercetin, very powerful vitamin C, age and excretion. I like to round out the program with DHA. It doesn't have direct effects on the pathways that we're talking about, but it does tend to offset some of the damaging effects of fructose in the human body. so those in terms of supplements would be good choices. Now, you know, the, the diet then that you hear me outlining would be one that is mostly plant-based this is the grain brain doctor who many people said was just the next Adkins telling us all to eat bacon bits. That's not what we're saying. It's not what I've ever said, but more of a plant-based higher fiber, colorful. That's where the bioflavonoids are. colorful type of plate. That's what we're looking for. It's more sustainable, it's better for you, it's better for your gut bacteria, and it will help bring down your uric acid levels.

So one of the things I often used was cherries, cherry extract.

That's right.

It seems a little contradictory because it's a fruit, got fructose in it. But, you know, I've often treated my patients with higher acid or out with cherry extract and found it very effective.

It is very effective. It's more effective in women than in men. but tart cherry is on the list. A cup of cherries, you know, that's what was used in several studies. As a matter of fact, if you look at the COVID of the book, and I just happen to have one right here, look at the O of the drop acid. That's the cherry. So you're, you're exactly right. Dropping acid, uric acid, using cherries been used for gout therapy for, for many, many years. And vitamin C, too. Vitamin C. question is a little newer to the game, but for a long time, gout patients were told to take vitamin C and or consume vitamin C rich foods, but not fruit juice. There's really nothing ancestral about consuming fruit juice. It's not like our hunter-gatherer forebears would have stumbled upon trees with cans and bottles of fruit juice hanging from them and then consume them. Powerful effect to load. Yeah. You know, that's really unlike anything that our physiology is ready for. It's staggering how many people have really been brainwashed.

I think that fruit juice is a healthy drink.

Yeah, it's a lot of eat the fruits, get the juice. I live in Florida and, you know, orange juice.

Orange juice. Yeah.

Nature. Anita Bryant, you're not having. You're not having orange juice. What's wrong with you? You didn't have your breakfast until 12 o'clock noon. Again, what's wrong with you? I guess there are a lot of things wrong with me because I take plenty of criticism. But that said, it's the Orange Juice Growers Association, or whomever is the lobby that wants us to do certain things. The whole grain goodness of these processed cereals that we think is heart healthy, all of this messaging that we've been getting for years and years is hugely effective. and it's what people think is the right thing. You know, your breakfast is the most important meal of the day. Maybe it is, but it doesn't mean a powerful carbohydrate load at 8:00 in the morning is going to set you on your way. So, you know, that's our mission, you and me and so many people, is to kind of, you know, let people hear the other side of the story so they can be better architects of their health destiny. Yeah.

I mean, I think that's a problem, is that, you know, All the things that we're pointing to that we've both talked about forever are all really driving this final common pathway of insulin resistance and inflammation that's sort of underlying all these chronic illnesses from heart disease to diabetes to cancer to Alzheimer's, depression, lots more. And what you're seeing is a lot of this may be mediated by this mechanism of uric acid, which is directly related to these sort of load of fructose that's in our diet since probably the 1970s when high fructose corns are starting to be used in almost all industrial food products. And it's now really the majority of the sugar that we're consuming. And it's quite different than regular sugar. I mean, but even regular sugar can be a problem, right? Even if you just have regular sugar, it can cause this, right?

Because regular sugar has high. It is immediately. And fructose, you know, it's fructose in this case bound to glucose, but that separation takes place immediately in the small intestine that we then liberate fructose. And interestingly, here's another bit of trivia, but I think it's relevant in our, because the amount of sodium added to our foods, the amount of sodium that people are consuming, that this salt in our bloodstream activates enzymes that actually create fructose from glucose. The enzyme is something.

Wow. Wow.

Aldolase reductase. But so we're actually making fructose in our bodies from glucose to again, you know, fructose.

It's a double whammy.

Yeah. And, but again, and it's this sugar in our diets. And, you know, as you know, every five years our government puts out these guidelines. And we wrote Dr. Casey Means is an individual involved in getting out information about blood sugar. I'm sure you know her. And- and- been on our podcast before. We wrote an op-ed in Medpage today that was published February 21st of 21. It was a letter to President Biden saying, look, basically all the scientists who were involved in creating, you know, giving the information for the USDA to make this policy indicated that we need to consume less sugar. And yet they didn't lower the number of calories derived from sugar is still 10% what the government recommends. That was not during the Biden administration, but we were hoping that there could be some intervention to get it down to about 6% of total calories derived from sugar because it's the big villain. I mean, you know, really? people that you've interviewed have talked about it is the big villain.

So, David, what about flour? Because, you know, in my world, there's not that much difference between flour and sugar. Is that also an issue?

Of course it is. And so, again, you know, anything we create these feedback loops whereby we enhance these processes that are designed to be enhanced to keep us alive. And as it relates to flour, you know, that will directly elevate our blood sugar, what does that do? That increases insulin resistance. What happens to insulin when it's not working very well? It goes up. Now here's where the feet forward plays in. It's really quite fascinating. Higher levels of insulin, that can be a consequence of eating refined carbs like flour, higher levels of insulin increase uric acid by inhibiting the excretion of uric acid, in the kidneys. So now we've tapped into the whole process of uric acid elevation, everything you and I have been talking about, by virtue of the fact that we're eating these refined carbohydrates. So again, you know, that just activates this mechanism saying, oh, my gosh, you're not going to have food very soon. You had better start making fat. You better start retaining salt because you may not have water. You better start increasing your sugar production through the liver. a process called glucogenesis to power your brain so you can find food. You know, that's our ace in the hole. We got a great, we're not the strongest, we're not the fastest, but we have this brain that can help us find food. And, you know, our biggest issues throughout our history were starvation and predation. In other words, either. Either we found food or we were food for somebody else who would eat us. and again, what has saved humans has been the fact that we got this big brain. I don't know if it's saving us anymore, another discussion perhaps, but the fact that we can survive by our wits, that's what it's been, that we can find food, we can realize we don't want to go to a certain place because there might be an animal there that can eat us. This is how we survived.

Yeah, it's pretty striking. So, David, let's go into some more granular details about uric acid. When we talked about the foods that raise it, we talked about foods that can help lower it, essentially plant foods, plant rich foods, cherry extract and so forth. There's also interaction with medications, a lot.

Of medications that can increase uric acid. Can you talk about those? That's right. I think some of the biggest players as relates to medication include aspirin. You know, we, over the years, everybody was told, take aspirin, it'll keep you from having a stroke or having your children more naked. Oops. Or whatever.

Yeah.

So everybody should be taking aspirin. Aspirin. will raise uric acid. I think the other big players are water pills or diuretics. These directly increase, are associated with increased uric acid, but there are a number of them. The proton pump inhibitors, that's a drug.

Acid blockers.

Acid blocking drugs taken by 15 million Americans over the counter for crying out loud are, you know, in stuff that we've been talking about for the past few years, significantly associated with risk for Alzheimer's, and stroke. And now we know that a powerful mechanism, we can get back to it, is maybe through the elevation of uric acid, beta blockers, xylitol, we don't consider it a drug, but I include it there so I don't forget it, as a sugar alcohol that's very commonly added to food, significantly increases uric acid. A lot of health foods have it.

And is a way of getting rid of sugar. So you might be thinking you're helping yourself on one hand, but on the other hand, you're putting in these sugar alcohols which can be harmful not just to uric acid but also your microbiome and other.

Oh, for sure. And even drugs that enhance nitric oxide for erectile dysfunction will raise uric acid. And let me unpack that just a little because I think it's really important.

Oh, wow.

Erectile dysfunction.

Well, sex makes you live longer.

So maybe it even's out. I don't know. Maybe. So erectile function requires blood flow. and the real mechanistic issue that seems to have been defined for erectile dysfunction is lack of blood flow because of poor function of nitric oxide that would have allowed blood flow to allow an erection to take place. Turns out that men with elevated uric acid have about a 36 to 38% increased risk of being diagnosed with erectile dysfunction because as I mentioned earlier, uric acid compromises the functionality of nitric oxide. So, you know, and here's a drug that's then used for the erectile dysfunction, but that can further increase uric acid. So, wow. I think it's so important that people understand that. I mean, it's some interesting biochemistry. Other things that are associated with elevated uric acid include niacin, vitamin B3, and certain Parkinson's drugs like levodopa, and then a drug that's used for people with certain types of respiratory problems. called theophylline. So that kind of rounds out the list of the big players as it relates to drugs. But aspirin gets a lot of press when you, you know, I would ask your viewers to Google two things, uric, U-R-I-C, and the word metabolic. All the literature will come up and there's a lot of it. And included in that will certainly be, you know, lists of drugs that are associated with increasing uric acid. It's so far beyond gout, you know, and, and kidney stones. It is a central, as the article title stated, a central player orchestrating much of our metabolic Mayhem, as I call it in the book.

And then talk about Alzheimer's, because that's your specialty, is neurology. And it seems that this is also connected to Alzheimer's that you're casted may be linked to the risk.

Well, you would expect that to be the case, and it really is. There was a big study published in 2018 that looked at individuals, 1600 people, followed them for 12 years. And these people had at the beginning of the study a measurement of their uric acid level and an MRI scan of the brain and neurocognitive testing. In other words, how well is their brain working? And those neurocognitive tests were repeated six times during the 12 years. So let's say every two years. And what they found is 1600 people, is that those individuals who had the highest level of uric acid had an 80% increased risk of being diagnosed with dementia, a 55% increased risk of that dementia of having actual Alzheimer's disease, and 165% increased risk of what's called vascular or mixed form dementia. So it's powerfully threatening to the brain as you might expect. Why? The brain requires fuel, sure. But if we induce insulin resistance by having high levels of uric acid like we've talked about, the brain requires insulin to use its glucose, that's for sure. But insulin in the brain also acts as what we call a trophic hormone. It nurtures the brain cells. When we compromise insulin's ability to nurture the brain cells, we take away the support, we take away, you know, the nurturing, the loving, the, you know, what gives the brain cells what they need to function. So when we also consider how uric acid threatens nitric oxide and that threatens blood supply, that explains why we see such an increased number of small strokes in the brain. There was another study that it was not a prospective study. This is a study that looked at a group of individuals 168 individuals. And it's a study done right now. They took a group of elderly people. They measured their uric acid. They did some neurocognitive testing to see how their brains are working. And they did MRI scans to the brain. What did they find? 228 people. They found that those individuals who had the highest level of uric acid were four times as likely to be demented.

Wow.

Fourfold increased risk of dementia. Those who had the highest levels of uric acid. And, you know, it all makes sense when we understand that we're compromising blood supply, we're increasing inflammation, a central pillar of Alzheimer's, and we're messing up how insulin works throughout the body, including the brain. Powerful mechanism that the brain doesn't, you know, doesn't appreciate. I've had several very interesting conversations with a colleague of yours, Dr. Dale Bredesen, and he is vigorously involved in looking at uric acid levels as it relates to Alzheimer's and then getting uric acid levels to come down as, you know, one of the important pillars he uses. He looks at a lot of different things, unlike modern medicine that only wants to find one intervention to fix that problem. but as you know, Dr. Bredesen is reversing Alzheimer's by looking at multiple inputs and certainly moving forward, uric acid is a powerful player. Now, David, this isn't something you may.

Never come across, but I've come across it and it's sort of an anecdotal observation, but sometimes uric acid levels are very low and, and usually they're sort of written off as irrelevant, but I've noticed that they're often correlated with heavy metal toxicity. Have you found that? Is there any data on that?

Yeah, there is. Matter of fact. And, you know, the whole notion of us defining the upper limit of good uric acid speaks to what we call this belt U shaped curve or Goldilocks zone. I don't want to say sweet spot, you know, for obvious reasons, but that there is an ideal place for anything, whether it's your blood sugar, the amount of sleep that you get, you name it. And it may be that this is the case with uric acid as well. While I've not seen specific correlation with heavy metals, there is some discussion that uric acid does represent some form of an antioxidant in the body and having really low levels of uric acid might be threatening. That data is really based upon the observation that cachectic or really, really thin elderly people with very low levels of uric acid and, and with dementia and have very low levels of uric acid. And I think the explanation that's been offered, because I've asked actually Dr. Richard Johnson about this. Yeah.

Yeah.

He says, you know, these are people that have no body mass whatsoever. And their, their food consumption is such that they're not going to, that the uric acid level is going to be really, really low. So he looks upon it more as an effect as opposed to being a cause. And therefore, you know, we don't really have the ability to define what is too low a level of uric acid. I think defining the upper limit these days makes sense. The average uric acid level in 1920 was 3.5. Now the average level is above the ideal level. The average level is 6.0 in America.

Interesting. You don't think it's necessarily correlated with heavy metals?

I would have to think about that. I won't just offer an off-the-cuff evaluation, but how interesting it is that the consumption in 1900 of humans consuming fructose, we would consume about 15 grams a day, a couple of apples, pieces of fruit, whatever. Now the average daily consumption of fructose, I'm not saying sugar, of fructose is 55 grams a day. That increase in fructose consumption, those curves perfectly line up as you would expect with uric acid levels over time. so, you know, everything's fitting together. And when we look at, at obesity rates, a third of adults being obese right now, as you and I have this conversation, that number is going to be 50 in the distant future, which is 2030. Hey, that's not the distant future. You know, I know we're trying to be evergreen, but that's eight years from now. That'll be 50 of adults in America are not just overweight. are obese. And that is a scary, scary proposition. I mean, how are we going to care for those individuals? You know, we've seen that lifespan is decreasing in America pre-COVID, certainly COVID has added to the decline, but it was declining pre-COVID. And that makes sense now when we look at these numbers and I look at them through the lens of uric acid. The reason being is I want uric acid to be a new important metabolic marker. I'd like people to go to the doctor and have their blood sugar measured, their fasting insulin measured, their waistlines, blood pressure, and uric acid as well, a very important and powerful biometric, not just because it's a biometric and we can look in and say, Aha, it's elevated, but we can fix it. You know, getting your uric acid level down, really is mechanistically a way to regain metabolic health?

I think this is staggering. I just want to recap everybody about, so that you really understand this. First of all, take us to why uric acid briefly is such an important thing to measure at your doctors, what the numbers should be, and what the main foods that cause to go up, the main foods that cause to go down, and then we'll follow up with what are the supplements to take and how do we support that?

Sure, but let me preface that if I could buy a and I don't mean anything rude by this, but it's something again that those of us in functional medicine have come up against over the years. And that is simply the idea that your mainstream doctor may be unaware of the relationship of uric acid to metabolic issues. And I would say simply the query would be, Doctor, please just Google uric or uric acid and the word metabolic. That's all you got to do. If you want to do it on PubMed, all the better, right? But to be fair, most doctors, many of us, you know, we were told that uric acid is only important as it relates to gout and kidney stones, end of story. And if you don't have gout or kidney stones, you have nothing to worry about. Even if your uric acid level is sky high, that just is not the case anymore. We interventional trials using drugs where blood pressure is lowered using allopurinol that lowers uric acid. So, you know, these are done, these studies even in adolescents published in the Journal of the American Medical Association, adolescents who, you know, now 10% of kids between the ages of 12 and 19 are hypertensive. 10%. So metabolic issues are, are something that are affecting younger and younger people. We've got to pay attention to this and uric acid is playing a very important mechanistic role. So preface my response by saying lovingly, kindly mention to your doctor, hey, as a matter of fact, I saw this podcast with Dr. Hyman and I learned that uric acid might be a little bit more important than just gout and ask him or her to look into that. So first and foremost, fructose, it is, as Dr. Lustig says, It's the alcohol without the buzz. It is profoundly threatening to us. We've known that since the Lancet published it in 1970. But now we understand how and why. And how and why has to do with how it's metabolized into this central player, uric acid, no longer just re-associated with gout and kidney stones. So by and large, in our foods, It is fructose.

But if it's also sugar, it's also flour. It's anything that's sort of a refined starchy carbohydrate, which has sugar in it, which are carbohydrate get converted to fructose when you eat them. That's right.

And it's mostly high fructose corn syrup, but it's, you gotta understand it's more than just that. Anything above 11 grams per day already triggers that enzyme to convert your blood sugar into fructose, making even more. So, you know, we've recently seen a lot of, a lot of press about wanting to recommending to us to lower our sodium. We've known that for years, but now we have another reason to do that because high levels of serum sodium will convert, as we say, the blood sugar that we have into fructose, adding fuel to the fire. So by and large, it's fructose. If your uric acid is elevated, you want to cut out the fructose in your diet, but you may eat fruit. You pretty much want to do it anyway.

Nobody should be having high fructose corn syrup period. I mean, if you say to me, what are the two things that we should never eat? It's high fructose corn syrup and trans fats.

And then immediately cuts out like 95% of processed food. Well, what am I going to eat? You mean I can't eat something out of a box? No, you shop for every other grocery store and you have foods that don't have a barcode that they might even have to weigh. My gosh. That's right. That's right. The other contributors are alcohol. And again, some wine, a glass or two is fine. and you know, the studies actually did not delineate between red and white. I would say red based on its bioflavonoid content would probably be a better choice. But beer is a big problem. You wonder why people have these beer bellies because it's purine rich and contains alcohol and hard liquor as well. The other issue would be purine rich animal based foods. All animal meats have purines in them. but it really depends on what your uric acid level is. And to that, I would say so six ounces of chicken, if you're a meat eater or steak or whatever it may be, is going to be acceptable. But higher purine foods are things like shellfish and scallops and small fish, the anchovies and sardines that we've all favored over the years for other reasons. Yeah. That, you know, lower in, in bioaccumulation and certainly higher in good fats. But that said, you may get away with it, but you won't know until you follow your uric acid level. And what I'm saying is see your doctor on occasion, see where you are today with your uric acid level. To know your uric acid level might be as simple as picking up the phone. I don't people pick up the phone anymore, I think, or reaching in your pocket. I guess.

Hey, Siri, call blah, blah, blah.

Get my uric acid level.

Do you want to know my secret for living a long and happy and healthy life? Well, all I have to do is check out my weekly newsletter, Mark's Picks, where I share my favorite tips for health, longevity, well-being, and lots more. Check it out and the link below. Listen, you have leaned up brilliantly why we should be caring about uric acid and why people should buy your book, Drop Acid, because it really explains this in great detail and helps you understand what to test for, what to look for, what you should eat, what you shouldn't eat, and also what are the other things you can do to protect yourself. And you mentioned, you know, some medications that we should be wary of diuretics, acid blockers, aspirin and others that people should be cautious if they're taking these to pay attention and check their levels. And then lastly, there are a number of different natural products and supplements that can help bring it down.

We mentioned cherry extract, but you also mentioned a few others. Could you just kind of summarize those briefly? Sure. The big player would be question. And I'm certain you've had people on your program who've talked about question from other perspectives. as a senolytic perhaps being able to help us get rid of aged immune cells as an antioxidant, it's rolling inflammation. But now we recognize that quercetin actually works in the same way as the gout drug allopurinol. It targets an enzyme that is fundamental for producing uric acid called xanthine oxidase. So it is a xanthine oxidase inhibitor like the drugs used to treat gout. Even more potent might be another bioflavonoid that's called luteolin. So I'll give you dosages. I would consider, I'm not your healthcare practitioner, but the typical doses that will work would be quercetin 500 milligrams a day. Luteolin would be about a hundred milligrams a day. Vitamin C, which aids in excreting uric acid, and your vitamin C has been the darling supplement. for gout patients for decades. And that would be, again, about 500 milligrams per day, maybe a thousand milligrams of DHA would be reasonable. Again, not that it's having a direct effect on uric acid, although I think it does, but because it offers an offset to other things that are going on. You know, it decreases inflammation, it stimulates the production of something called BDNF, which we need for brain cell health. offsetting the damaging effects of this insulin resistance that people tend to develop. So I couldn't help myself but include DHA in the recommendations. To be sure, there are other issues that we should consider in the time we have left, and that would be that sleep plays a role, that not getting restorative sleep is associated with increased uric acid, and that sedentarity, meaning sitting on your rear end a lot and not getting out and moving, will be associated with elevated uric acid. And one other point as it relates to exercise, I think it's really important, that if you suddenly engage in a level of exercise that's far more vigorous than you are used to, you will break down some of your body tissue, some of your muscles, for example. You go on a long run, you'll break down muscle tissue and that will transiently increase what are called purines in your body, and that will raise in the short term a uric acid. Interestingly, we know that if you fast, you're going to raise your uric acid levels transiently, but ultimately that fasting is going to do good things for your metabolism. So again, we're thinking that fasting and time-restricted eating are all, in fact, I put it in the book, all good ideas as it relates to metabolic health in the long run. But if you're testing uric acid during a fast or when you're deeply into ketosis, it will momentarily be a little bit elevated. The messaging here is take a chill pill, take a deep breath, it's gonna be fine, you'll be better off when it's all said and done.

Amazing. So everybody needs to sort of get this. We need to pay attention to uric acid, we need to test it, we need to change our diet to get rid of the high fructose corn syrup, add in a lot more plant foods and a number of supplements, and we can really mitigate this risk. not just a bystander molecule that we check and see it's elevated in the context of diabetes, but it actually is one of the mechanistic drivers of a lot of these problems.

So it's simple. That's right. It's in the driver's seat. It's orchestrating. So, and again, the story about how we got here from, you know, 14 million years ago is really so interesting. You know, when we well, when researchers look at hunter-gatherer populations that are still living on the planet in South America, for example, we find that A, their uric acid levels are really low, and B, they have a variety when you look at their blood work and other markers, they have very low levels of fasting insulin, their blood sugars are lower, their insulin sensitivity is higher, their bone density is higher, their visual acuity is higher, blood pressure is lower, the raising of blood pressure with age isn't happening, leptin sensitivity is maintained. So all the things that we talk about that are related to better metabolic health are seen in those cultures that haven't yet stumbled on the sugar and whose uric acid levels remain low.

It's amazing. So people who have you listening to this, I hope you learned that we're in trouble because of all the high fructose corn syrup and the fructose and everything that we're eating is as well as the sugar and starch that uric acid is such a big deal that we pretty much ignore it. I obviously followed it in my lab test for years but never really understood the depth of how it interacts with our biology to cause all hosts of chronic diseases and that there's a way to fix it. So, David, thank you so much for writing your book, Drop Acid: the Surprising New Science of Uric Acid, the Key to Losing Weight, Controlling Blood Sugar, and Achieving Extraordinary Health. It's available. You can go get it anywhere you get books. Go to drpromoter.com/books/drop-acid. If you want to learn more, I encourage you to get the book, share it with your friends and family, share this podcast with your friends and family. I bet you they are going to be very interested in what David has to say. He's always coming up with the newest and most interesting things from brain-brain to brainwash to the book about the brain and gut connection, the Brain Maker. So David's really been on leading edge for so many years and I love you, David. I love your work. Leave a comment, let us know how maybe you've struggled with uric acid and what you've done to fix it. Subscribe wherever you get your podcast and we'll see you next week on the Doctor's Pharmacy. If you love that last video, you're gonna love the next one. Check it out here. What is our immune system and what does it do? And of course, the AIDS explosion led to developments in immunology that we'd never seen before. It accelerated science in immunology. And now.