What Is Uric Acid and How Does It Predict Your Longevity : 1321

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Uric acid levels, which were averaging about 3.5 in America in the 1920s, now are averaging 6.0 in American adults. And that increase is in lockstep with our increase in fructose consumption. Those who had the higher levels of uric acid above 7 experienced an 80% increased risk of developing dementia, a 55% increased risk of developing Alzheimer's disease, and they had 166% increased risk of what is called mixed or vascular dementia.

If I had known this when I was 20, it would have changed everything and it probably would have saved me a million dollars. It's interesting that your background is neurology as well. What do we know about uric acid and lining of the nerves? Myelination, neurotransmitters, things like that. You're listening to the Human Upgrade with Dave Asprey. Hey guys, quick reminder. If you're listening to this on your.

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So you're going to learn in this one from one of the great functional medicine doctors out there, what uric acid does to you. Why it's a key health marker and a major indicator of whether you are getting chronic degenerative diseases. And this is true at any age. If I had known this when I was 20, it would have changed everything and it probably would have saved me a million dollars later. So in the show, you'll learn how to measure your uric acid levels, what they mean, and you'll also learn about a new book that has the best name of a book I've seen in a long time, and it's called Drop Acid, which is like the best, most kind of creatively naughty, yet completely accurate title ever. So, Dr. Perlmutter, my friend, welcome back to the show and thanks for a hilarious book title.

Oh, thank you. It's, as we were saying before we went on, just great to see each other.

So what you've done in drop acid is identified. Okay. There's a level of something that medicine has looked at for a specific condition and said, oh, wow. Fluctuations in that level tell you all sorts of things, including an early indicator for diabetes, obesity, cardiovascular disease, and Alzheimer's. Those are the big four killers from my anti aging book. Those are the things that take out most of us. You have to take care of those if you're going to live a very long time. Like, first, don't die so you can live a long time.

It's not, you know, the number one cause of death isn't a virus or anything infectious. It is a consequence of our disrupted lifestyle. And it really. The history of this mismatch, if you will, between our genes and our current environment, or what we call evolutionary environmental mismatch, goes back as it relates to uric acid and the metabolic issues that we're suffering from. This can be traced back to about 15 million years ago, during the middle Miocene period when the Earth became cooler. And there was a strong selection pressure on our primate ancestors, favoring those who had whatever genetic mutations might let them make a little bit more fat, make a little bit more blood sugar to power their brains, and they would survive and pass those genes on to the following generations. And that happened all the way to us. And we've identified that there was a suite of genes in mutations that took place over more than a million years in an enzyme called uricase that breaks down, as you would guess, uric acid, such that these primate ancestors lost the ability to break down uric ace. So their uric acid levels were higher, and that provided a signal in their bodies that Food was scarce. Make fat, store fat, raise the blood pressure, raise the blood sugar, and we inherited that thrifty genome. Even to this day. It was helpful for our hunter gatherer forbears because they might not know when their next meal is coming. But, you know, ever since agriculture and certainly a lot more recently, we've been kind of targeting that whole mechanism to make body fat and store it. And now we have this mismatch whereby fructose, which is the signal, fructose, fruit sugar, becomes uric acid in your body, in my body, in the bodies of everybody on the planet. And that's a signal saying that we've got food, scarcity is coming, we better make fat. So now that we understand that we can target uric acid, you can measure it at home, you can get your doctor to measure it, and then we can lower it. And that is turning out to be a really powerful player to rein in a whole suite of metabolic issues.

All right, this sounds really promising for all the biohackers there. And also, you might not be a biohacker. You might just say, well, I have this weight that won't go away and I'm tired of going to the gym all the time and it not moving and I'm tired of trying a keto diet and it not moving and saying something's wrong. Well, this is an early indicator, so we can incorporate this. And what you brought to my attention when a box arrived and I opened it up and it says drop acid, and there's.

What did you expect would be in that box?

Coming from you? You never know.

Vinyl Hendrix albums, first of all.

Exactly. I dug through those. The tie dye. Now, it didn't just have a copy of your new book in it, it had a meter.

Right.

One of these meters, which measures uric acid from a little bloodstick. Same as you would with an older blood sugar meter if you don't have the continuous glucose ones. Or you would with a keto meter. So it turns out a little tiny prick on the finger really, really helps. And first off, you sent me one. Thank you. But what does a meter like this normally run?

I think they're about $90 or somewhere between 80 and $90. And I think they come with 20 sticks to measure. And the good, you know, unlike measuring your blood sugar every day for people who don't have a cgm, this is something you do every two to four weeks because it's not going to vary that quickly, depending on, of course, how aggressive you are about lowering it. But the nice thing is it Records. I don't know if you're able to see that. That was my most recent measurement, 4.7. But it will record your history of measurements and allow you to see what the impact is of your change in lifestyle, which is what it's all about. I mean, it's why we wear, you know, wearable devices to track our sleep, to track our blood sugar, because once we know where we are, we can observe how our lifestyle changes affect those parameters. And now we have a new parameter to, to look at, which is measuring our uric acid.

Okay.

And I just want to say that, you know, here in the United States, we're kind of a little behind other countries. For example, Japan has been studying this and really actually intervening with patients who have elevated uric acid and other metabolic problems for decades, for at least a couple of decades. They put out a really fascinating study back in 2009 where they followed a group of individuals, 90,000 people, adults, 42,000 men, 48,000 women. They followed them for eight years. They measured their uric acid at the beginning of the study, and they found that with people who had a level of seven, which is very common, or greater, their risk of what we call all cause mortality, meaning dying from anything whatsoever, was increased by 16%. Their risk of death from cardiovascular issues was increased by 39%. Risk of death from stroke increased by 35%. And what I found really fascinating was that for every point elevation above 7, there was an additional 8 to 13% increased risk of death from, again, what's called all cause mortality, meaning you died from something. So, you know, this is a big study, went on for a long time. That's compelling information, especially now that we know that uric acid is signaling our bodies. It's sending an alarm signal to our entire body, saying, winter is coming. And it's telling our bodies, get ready. Reduce your metabolism so it compromises mitochondrial function, make body fat, lock up the body fat, store it so you can't tap into it, and even raise your blood sugar. So you can do what? Power your brain. So you can avoid two things. You can avoid starvation, and you can avoid predation, meaning getting eaten by another animal. We, you know, we have a pretty sizable brain. We need to power it. So this is a signal then that's telling us to get ready. And it's very interesting because what it does, and I think many of your viewers, especially those who really consider them kind of deeply entrenched in the biochemistry, what uric acid does is it shuts off AMP kinase, and I'm certain that many of your listeners viewers know that we want AMP kinase pathway lit up all the time because which is why coffee, right? Why coffee? Why exercise? How metformin works to keep diabetics blood sugars lower. Quercetin, berberine, lots of things we could do to keep our AMP kinase lit up because when uric acid is elevated, shuts that down and it tells us don't burn your body fat, store your body fat. It actually shifts this all whole metabolism over to another way of dealing with amp. And that's through what's called AMP deaminase. And this is exactly the shift that happens for example in bears prior to their hibernation. They're trying to make as much body fat as they possibly can and ratchet down their metabolism so they could live in the cave for however many months. And they need to make this body fat during the fall when they're eating the fructose, eating the berries. So unless any of your viewers think they're going to hibernate for several months, it's not what we need to do. We want to be burning our body fat, we want to be keeping AMP kinase active, keeping our blood sugar lower. And I think you mentioned something a moment ago, I think it was really very important about people who are struggling with their blood sugars, their blood pressures, their body weight, doing all the things right. They're listening to every podcast, trying to do their best, whether it's keto or paleo or whatever, but they're sticking to these plans and maybe making progress. But they're always wondering if there just isn't something missing, some other little piece of the puzzle, that little corner piece in the jigsaw puzzle that when you get it, you go, yeah, finally. And I would submit that for many people it's going to be targeting specifically and we'll talk about it, their uric acid.

I have to say, having looked through your book and having just chatted with you about this, I wish that I had included this in Superhuman. Because the percentage risk of lowering of all cause mortality, it's a major thing you do when you're looking to live a long time. And the percentages that you cited there are very meaningful. I went through many, many interventions and they're saying, okay, this one looks like it works for this, this one looks like it works for this. But uric acid as a signaling molecule is something that a lot of people haven't talked about. So maybe this came out of Japan or something. But how come you're the first person in the west who's talked about this? It seems like it's a big enough thing.

I'm absolutely not. I. You'll note that drop acid, which is something I think we should all do in the context of uric acid, is dedicated to a man named Richard Johnson, M.D. Dr. Richard Johnson University of Colorado. He. He's done the pioneering work and really began to raise the. The level of understanding of uric acid's role. But again, this is something that's not uncommon in many other countries around the world. In America, it's all about, you know, lowering your cholesterol and hope for the best. You know, we really see that the mentality here in North America is kind of live your life however the heck you want, and when you're finally cognitively impaired, your blood sugar's going through the roof or whatever it is, we'll fix it for you. Don't worry. Pharmacy is here. You know, main mainstream pharmaceuticals are here to save the day. That is just a perversion of reality, especially as it relates to the brain. And, you know, that's what really got me started when I reviewed studies like a Japanese study looking at 1600 people and followed them for 12 years. And every two years, they did an assessment of how well their brains were working. What they found was after the 12 years, those who had the higher levels of uric acid above 7, they experienced an 80% increased risk of. Of developing dementia, a 55% increased risk of developing, specifically Alzheimer's disease. Oh, did I say. A disease for which there is no treatment. And they had 166% increased risk of what is called mixed or vascular dementia. Now, you know, I'm a neurologist, and in dealing with these problems from a interventional, pharmaceutical perspective, there's very little. From a pharmaceutical perspective, there is really nothing yet that we have that can arrest this problem. It's very, very challenging. And it gets me both from my professional perspective and from a personal perspective, having dealt with this in my dad as well. So anything that we can do that has an impact like that I think is very, very valuable. But the thing about this metabolic signaling is it has huge impacts on cardiovascular disease, on hypertension. We mentioned Alzheimer's, and even various forms of cancer like pancreatic, colon, and breast cancers that are related to this metabolic mayhem. And that's being kind. So it's a new and very exciting tool. And the exciting thing about it is it's something that we could take home. It's not like you have to have your genome sequence and then send it off Someplace and hope that you get back an interesting interpretation that might or might not be effective for you. This is really very, very straightforward.

I want to know what do we do to raise it? What are the things that are cranking this up in people?

So for many years, people have known that elevated uric acid can be a problem, generally in the context of something called gout, where you develop painful crystals that accumulate in your great toe. And it's traditionally been described as the king of diseases and the disease of kings, meaning people who ate a lot of rich food, a lot of food rich in what are called purines. That's a lot of meat, but specifically organ meats, liver and kidney. And it turns out that while those can relate, in our modern world, the big player is fructose, or fruit sugar. Not necessarily the fruit sugar found in an apple, but the fructose that's found in soda added to sauces. Actually, you know, found in more than 60% of packaged foods in the, the grocery store. Things like fruit juice, for example, that there's nothing natural about fruit juice. The fructose content will knock your socks off. Fructose is metabolized directly into uric acid. There are only three things that make uric acid. Alcohol, purines that I mentioned earlier, and fructose. And so when you see, for example, a combination drink that has both high purines and alcohol, which is beer made from yeast, so it's got a lot of purines, then we begin to understand why people get a beer belly. Because it's telling the body aggressively through two inputs, purines and alcohol. Rather make fat because winter is coming and gaining body fat and raising your blood sugar and your blood pressure are terrific things. They're weight wonderful things for 99% of the time on this planet, but not now. So until just recently, if you could make a little more body fat, you would survive because you had that backup resource for calories so that if there was no food, you might make it through, whereas the next person might not. And this again, we call this the evolutionary environmental mismatch. And I actually wrote my first paper on this whole concept of environmental mismatch 50 years ago, half a century ago, published that in the Miami Herald in 1971. I was 16 at the time. And I concluded that paper by op ed by saying, but what about us living today with the outdated machinery, meaning we have machinery that's really set up for the hunter gatherer times or even, you know, prior to that, when the world was a different place and What I'm saying is, if we can emulate those signals to our DNA and our physiology that have evolved to keep us healthy, we're going a long way to offsetting these incredibly powerful metabolic disruptions that are paving the way for, as we talked about earlier, the biggest cause of disease on our planet. And you know, to be clear, this uric acid is screaming, winter's coming. Make fat. And also important to recognize that it raises our blood pressure because it's a signal that we're facing dehydration. Now, that's a little bit more complicated, but understand, let me preface this by let's think about a camel. And a camel is getting ready to walk. It is walking across the desert. It's not drinking water for three weeks, and it has this great big hump. What do you think's inside that hump? Not water. Fat. Because when we burn body fat, we create two things. Carbon dioxide and what's called metabolite water. So fat is a powerful resource for us as humans. Yes, as a resource for calories, we get that, but also a hedge against dehydration, because when we burn that fat, we're making metabolic water. So it turns out that when our bodies think we're dehydrated, we turn on fat production. And why do we think we're dehydrated? Well, we might be dehydrated if we're not drinking enough water. But we can also signal that by raising our sodium when we don't have enough water to drink, our sodium level goes up, and that turns on a pathway whereby our bodies make fructose. Then that fructose becomes uric acid. And what happens? Our blood pressure goes up. We make fat so we can make metabolic water. How do you raise your sodium? Well, either with the playoffs or the super bowl, you park yourself on that couch and eat that bag of pretzels with a lot of salt, and your serum sodium goes up. You start making fructose, making uric acid, making body fat. And the next thing you know, you're signaling this entire alarm cascade. In this case, thinking that your body's becoming dehydrated and it's trying to protect itself.

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Couple questions for you there. Low sodium diets make people feel like crap and raise risk of heart disease. The current levels that the RDA has for sodium, for total sodium, raise levels of renin in the blood enough that it increases your very substantially your risk of cardiovascular disease. Higher stress means higher demand for sodium. And from many of the things I've seen, you get enough sodium and for me it's about 6 grams a day, roughly three times more than the RDA. Then I have a clearer head. I make stomach acid better. Increases in bone density, like, oh, there's all this good stuff from salt. And then we've got guys like Paul Saladino and Liver King and me, I've been recommending raw liver since my first book on fertility. Yet it's high in purines. So how do we, how do we look at that? I don't want people to lower salt because they're going to feel like crap if they do.

And they let me. Let's first tackle the salt question, then we'll get back to the liver. Uh, and first, the important thing about salt consumption is that yes, you're right, we do need some sodium. Uh, but there are two things that are extremely important and that is the rate that we consume it and the concentration by which we consume it. So if a person's eating a salty food that is going to give them sodium, which has, as you mentioned, some retrospective studies indicating that there, there, there are benefits. And we know we need serum sodium, you know, to be balanced. The, the trick is to follow it with water and therefore your sodium level isn't going to change. So you're right, but eating just salt in and of itself tells the body to make fat. I mean, this is something that cattle ranchers have known for a long time. Why do they put a Salt lick and out. So the, the cattle are going to lick salt all day long because it's making them. Your physiology thinks it's dehydrating and they increase their fructose production and make body fat. Now, as it relates to liver, which has huge properties that are helpful, the B12 availability, iron availability, et cetera, it's really all about the individual. I would say that the biggest issue by far and away isn't eating high purine foods. It's always been the fructose.

There you go.

Of gout, it was always the fructose. Back in the 1800s, the amount of sugar consumption in England was actually quite substantial, especially in its. In being mixed with alcohol. Alcohol. Then you, you layer on top of that the purines. And to this day, and we can speculate, we don't need to speculate. We, we know why to this day, when you look at a diet for gout or a diet to lower uric acid, go online, go to one of the institutions, their websites, it's all about lowering purines. And they're so loathe to talk about sugar. It's the sugar. It is clearly the sugar. Whether you want to talk to Nina Teichol or Robert Lustig or, you know, and these people who are trying to get this message out, Casey means it's all about the sugar. And yet, oh, no, no, you need to stop eating liver, you need to stop eating organ meats and venison and scallops and mussels, really, as it relates to uric acid, by far and away, it's the fructose. That's the thing that increased 1000% in American adults consumption going from 1970 to 1990.

In order, then the things that are going to raise your uric acid the most would be, number one is sugar.

Or let me give you the top.

Fructose, then alcohol, then liver.

Number two, fructose. Number three is fructose. Number four, purines. Number five, alcohol. And I don't.

Purines worse than alcohol. Really?

Alcohol and purines. I don't know if the order is right. Really depends on the individual.

Okay, fair point.

Alcohol needs a little bit of. We need to double click on that for just a moment. Because wine, it turns out, doesn't really have much of an effect because wine has offsets. Like fruit has offsets. You can eat fruit, wine has offsets, probably the bioflavonoids that target an enzyme that makes uric acid. So in women, retrospective food frequency questionnaire studies demonstrate that women who Drink wine have a slightly lower uric acid than those who do not. Men, Men. It's about a wash, it's about neutral. Hard liquor is associated with a slight raised uric acid level. But as I mentioned before, beer, beer is, you know, a big issue because of the alcohol. Yes. But also the purines. And once again, Japan is ahead of us on this by creating and marketing purine free beer.

Wow.

And I can assure you in Japan, this is well beyond the small percentage of their population that has gout. They recognize that purines make uric acid, which leads to high blood pressure, which leads to high blood sugar and obesity. So now you find purine free, purine free beer.

Wow. I did not know they did that. Why does Japan do so many of these cool things that we don't hear about here for many years?

Well, I think they got into trouble earlier than we did. Japanese people tend to eat a lot of umami flavored foods. Umami flavored umami foods are, are going to be very, very high in purines. And so they, they have a risk for high uric acid. And, you know, have been dealing with this actually for quite some time and then began to study, well, what is it, what else may be going on? What are the correlates that we're seeing with high uric acid. And they began to unravel and reveal to the rest of the world these really high relationships with various metabolic diseases. One study published I think 2016 by both Japanese and Turkish researchers is entitled Uric Acid in Metabolic Syndrome from an Innocent Bystander to a Central Player. Meaning, yeah, we've known that there's elevated uric acid that correlates with obesity, diabetes, hypertension, known there for a long time. But that study really made it clear that it's not just happens to be elevated in conjunction with these issues, it's causing it. It's playing a role with lots of research. I delineated it in the book, showing that when you intervene and stop uric acid production and don't even make a dietary change, that you can reduce hypertension, you can reduce weight gain. And in some of these studies, they actually raise the uric acid by giving humans what, fructose, placing them on a high fructose diet. But you know, frankly, you don't need to even do that. When you see the amount of fructose that adolescents and young adults are consuming these days in the form of energy drinks and sports drinks, along with soda and fruit drinks, it's breathtaking and it's no Wonder that that uric acid levels, which were averaging about 3.5 in America in the 1920s, now are averaging 6.0 in American adults. And that increase is in lockstep with our increase in fructose consumption. So you know, there have been variations in alcohol consumption, certainly going through prohibition, et cetera and purine consumption. As you know, more people adopt a plant based diet. But what we're seeing is still uric acid levels are skyrocketing. It's been estimated right now we know that in America one third of adults isn't just overweight, but is obese. A third of American adults is obese. And in the distant future, in 2030, that's way in the future, some distant future, that number is going to be 50%, the flip of a coin, obese, not just overweight. Right now, more than 70% of Americans is either obese or hypertension or or overweight. And this isn't that there's been a sudden change in our genome. It's an environmental issue. It's really based upon our choices that are so heavily influenced by industry.

There are a variety of what's called biogenic amines and these are things that are formed in the gut and purines are one of them, but so is spermidine. There's putresine, which strangely enough has benefits and negatives. But are the, are all of these going to raise uric acid?

No, I mean these are metabolites there from. So they're not. And these are actually, you know, created to some degree by our microflora, by the gut bacteria. But you know, having. That does kind of segue nicely though into the notion that there's an interplay then between uric acid and our gut bacteria such that higher levels of uric acid favor more or the, what are called the pro inflammatory bacteria. And you know, I always want to break it down, say, oh, that sounds terrible. We don't want more inflammation. That's always bad. No, diabetes isn't always bad. Body fat retention isn't always bad. It could be a life saving situation. Let's look at it in context. So having an increased amount of inflammation can be life saving and would have been life saving for our ancestors in helping them deal with various types of infection. Inflammation is an important life saving mechanism within your physiology. So the notion that a higher level of uric acid by increasing inflammation and increasing gut permeability might have an upside, I think, you know, it just changes our perspective a little bit. Similarly, the ApoE4 genetic allele is associated with increased risk for Alzheimer's. So obviously, under any circumstance that's a bad thing, right? Well, no, we know that in certain cultures that are equatorial and live in a very agrarian or a hunter gatherer like environment, carrying the APOE4 allele that we used to call the Alzheimer's gene is actually associated with a lower risk of Alzheimer's and certainly a better ability to combat certain infections, specifically parasitic infections. So getting back to the uric acid relationship to the microflora, we know that, for example, gout can be treated with what is called a fecal transplant by giving gout sufferers normal gut bacteria in the form of a fecal transplant. We've talked about it before. Their frequency of gout attacks goes down. So it's, it's a two way street. And, and again, hey, the various things that uric acid can do in your body are, are generally in the context of our modern world, where it's 365 days a year that we're signaling our bodies to get ready for winter. Make fat, raise the blood sugar, raise the blood pressure. You know, we have to think of it in the context of, gosh, for our ancestors, that was life saving. And that's why we're in this situation today whereby everyone walking the planet has inherited this uricase mutation. Wonderful review about this in Scientific American about how this all happened. And therefore, when we come upon the blueberries in the late fall and early, late late summer and early fall and it signals our body to make fat, well, that might have been great for our hunter gatherer forebears, but for you and me, who have access to fructose 365 days a year, it's sending the signal, oh my gosh, you're not going to have food. Winter's coming and it doesn't work for us.

This is one of those things about eating seasonally. If you do that, you're supposed to fatten up in summer, and towards the end of summer you would eat more omega 6 fats because there are more of them available which slow down your metabolism.

Exactly.

You tired and put you into hibernation. That's why bears do it. It's designed that way. But if we don't want to put on fat all summer long and then go through a winter without carbs, where our brains are slow and we're tired, you might want to eat seasonally, but maybe you don't need to load up quite as heavily, even on fruit towards the end of summer when it's available.

Yeah, and I would say if not just eat seasonally, but if you're planning to eat seasonally, in other words, load, not loading up, but eating more of those fructose rich carbohydrates. In the late summer, early fall, you've got to be all in on the entire rest of the plant. Meaning that once winter comes, your body should experience fasting and, or at least the very least time restricted eating. So it's, it's not really stick and choose from the, from the paleo menu. And so I'm going to do part of it, but not all of it because it's either, you know, it's a whole program. If you're going to emulate our ancestors, then you need to go to bed when it's dark, you need to have, you know, high quality sleep. And every aspect of what we assume our Paleolithic ancestors experienced.

Okay, I'm getting you there. And this is a way of monitoring. If you get your measures every two, every four weeks, you can see if what you're doing to probably just reduce your fructose, which you and I have been recommending for at least 10 years in the books that we write and all. But there are other markers that matter. Now I'm going to ask you this as an md, as a neurologist. If you had a random person from the population out there, you don't know much about them and you wanted a marker to predict if you got Covid, would you be hospitalized and you could either get their vitamin D level or you could get their uric acid level. Which one of those markers is likely to be more important?

Hard to say. You know, we've seen the data on vitamin D and we've seen the data on blood sugar upon entrance. I think that one of the most powerful tools for predicting outcome is called a tape measure around the world. Very sophisticated. But as they have it, In May of 2021, a study came out. Chinese researchers actually looked at 1,854 people and measured their uric acid when they presented to the hospital. And what they found was really quite interesting, that the risk of being one of three things going in the icu, being put on a ventilator, or death. And all three is what they called the composite score. But the risk of these things was between two and three times increased if you entered the hospital with a high uric acid level. So why would that. That shouldn't be a surprise because that uric acid level is going to be seen in people with diabetes and with hypertension and certainly with a high body Mass index or, or obesity. So it does have an effect on immune function. It does. I think we're just beginning to see how it relates to inflammation like we, we talked about a little while ago. But you know, again, there are interventional studies being done now where pharmaceuticals are used to lower uric acid. And they're, and, and we're seeing results in terms of things like body fat and blood pressure. How the pharmaceuticals work, like allopurinol, which is a gout drug, is it targets a specific enzyme called xanthine oxidase. That'll be on the quiz that's fundamental in the production of uric acid. Well, it turns out that that xanthine oxidase is dramatically inhibited by some exotic thing called quercetin. Who knew quercetin and luteolin, another bioflavonoid available at the health food store, target this xanthine oxidase enzyme almost as effectively as the drug? And so we see studies. One study from Oxford in British literature showed that giving Quercetin 500 milligrams a day in a group of 22 young men with elevated uric acid lowered their uric acid by 8% in two weeks. No other changes, just quercetin. And you know, we mentioned it earlier, quercetin powerfully targets AMP kinase. Who wouldn't want that? It's a senolytic, it's an anti inflammatory, it's an antioxidant. So I'm all in as it relates to taking 500 milligrams of Quercetin. I been doing that for quite some time along with 100 milligrams of luteolin.

Wow. Luteolin and quercetin. Right.

Strong medicine. It really, really is. I mean. Right, right. Just those two nuggets. I, I think for your viewers gonna have a really significant effect on lowering their uric acid. And you know, you were alluding to the fact that, you know, you do have friends who are all in as it relates to things like eating organ meats, for example. And I'm not saying you shouldn't do that. I'm not saying even though they're higher end purines, do you necessarily have to go on a program that eliminates them? You do not. Depending on your uric acid level. But let's say you do your best to eliminate the fructose, you're taking the quercetin, you're monitoring your sleep, you're doing all the right things, and it's still a little bit recalcitrant. It's not reaching 5.5. That's the number. That's our goal. It's still around 6. That's better, but not good enough. Then that person may want to maybe cut back a little bit on the purine rich animal foods and see what happens. But I think again, third time I've said it. The big players, the fructose, add in the quercetin, add in some luteolin, and certainly I think generally in most people, they're gonna see a pretty dramatic lowering of the danger signals screaming in your body telling you to make fat and store fat.

Now I got curious as we were talking about specific types of probiotics that produce uricase which breaks down uric acid. What's your take on probiotics for this?

Well, I don't think there, there's really much in the way of marketed, nothing marketed probiotics that do in fact supply uricase. Again to remind everybody, the uricase is the enzyme that in other mammals, for example, breaks down uric acid to allantoin. We don't have uricase. We have really zero as it relates to uricase enzymes. So we don't have that. Nor do the great, any of the great apes, the orangutans, for example, all, all of us have elevated uric acid four to five times higher than that of other mammals. Because it was a good thing, it was a good thing for us to become insulin resistant. Think about it, you know, we're always castigating insulin resistance and all those things. You know, you can put, whether it's talking to Gary Taubes or, or Bob, Rob Lustig, whoever, and that's in the context of our modern world. But you know, again, a survival mechanism. But that said, I think we're going to see it, I think more importantly, what we're going to see will be targeting an enzyme called fructokinase. And that's step one. It's so interesting. That's step one in the changing of fructose through several other intermediates into uric acid. If we can inhibit fructokinase, that will be the home run. There are a group of people who have fructokinase inherited deficiency and they develop a disease called fructoseuria where their urine is full of fructose because they can't metabolize it. They can eat sugar all day long, they don't gain weight, they don't develop any metabolic issues. So there's a lot being done to look at what would happen if we inhibited fructokinase.

Wow. So There's a. There's a whole. A whole pack of pharmaceutical or lifestyle things to do that I want to make sure that listeners. Luteolian. L U T E O L I N I take that every day. And question, what was the dose of luteolin that you recommended?

100 milligrams a day.

100 milligrams a day. So I, I take that almost every day. I don't always take the same thing every day, but that's. I don't.

In my sack, I don't either. And, you know, I was giving a talk recently. They talked about you had to do your disclosures because it was a continuing medical education talk, and I had to indicate I was a advisor to a certain CGM company and whatever. And then I said, another disclosure, I don't take the same supplements every day. And another disclosure is on occasion, I've eaten gluten and I'm still here. And another disclosure, my wife and I binge watch shows sometimes, sometimes on Netflix, truth be known. And yeah, believe it or not, yes, we're still here. But anyhow, I. I mentioned a moment ago that this really critical enzyme called fructokinase is what is needed for fructose to do its dirty work. For fructose to become uric acid and signal the body to really disrupt its metabolism, uric acid enhances this enzyme, fructokinase, so it stimulates even more and more of its own production. And we rarely see in physiology a situation where something feeding back actually makes itself even more active. Normally, we have what's called feedback inhibition, like we see with insulin regulating blood sugar. In this case, it's so desperately important for our survival that uric acid amplify itself. So, gosh, now that we know that, man, oh, man, knowing what your uric acid level is, taking the quercetin, cutting your fructose, taking the luteolin, restorative, sleep, get some monitoring device. I use an OURA ring. I'm not on their board. I'm just saying I do. And it's very helpful, know how well you're sleeping and, and really get in touch with your uric acid level and finally take that last edge off in terms of your metabolic challenges.

I. I love it. I just did a little quick sleuthing as we were going through this. I'm looking at probiotics, and it looks like there are some species of Lactobacillus plantarum, which is a common probiotic. In fact, you probably use plantarum in some of the things that you've created.

All of the things I create all.

The things you created. And there are specific subspecies that grow on buffalo milk, which is probably similar to yak milk, but it's grass fed. It has to be. So likely from grass fed milk would be the same from cows or cassava or sweet potato. Right. And cassava and sweet potato are generally lower toxin carbs that I recommend. I think those are ones that you would also recommend that don't have any fructose in them.

Right? Hard to say. I would say probably what you're saying is true. But you know, fructose in trace amounts is seen in a lot of vegetables though the name fructose comes from fruit sugar. And I want to be clear, we're not saying in any way. The data does not indicate that we shouldn't be eating fruit. You know, an apple a day keeps the doctor away. Five apples a day and the doctor you will pay. Meaning, you know, if you want to have an apple, go for it, have an apple. Or to make sure, eat the skin. Cherries are actually a great idea for people who want to control. That's if you look at the, the O on drop acid, that's a bucket, that's a cherry and falling from the sky, the indication there is that it's bringing down your uric acid. So tart cherry has been used as gout therapy for decades. And why? Because it works. It does lower uric acid specifically targets that enzymes anthian oxidase. That's involved in the creation of uric acid. I think the other thing I want to just get back to just a moment is the notion that not drinking enough water, you know, grandma said or mom said, you got to drink a lot of water. They said a lot of stuff to us and they always said breakfast was the important meal of the day, most important. But I think, you know, nowadays it's not necessarily what mom told us to eat. But I think the bigger story is when do you break your fast in the day. But, but having said that, you know, the idea of, of eating some fruit is appropriate. You know, an apple has in it some bioflavonoids that are helpful in reducing uric acid formation. Has vitamin C, which helps us excrete uric acid and it's got fiber that slows our absorption of fructose. So the liver can handle it. We're not going to spill it over into the intestine where we then absorb it and you know, again, pave the way for activating uric acid. So, you know, by all means fruit is still very much on the table. But again, there is nothing really salubrious about drinking a 16 ounce glass of fruit juice. It may as well be a Coke.

Well said. And if, when people give that stuff to kids, it even drives me crazier. Kids don't need that. It's just bad for them. And kids can drink water, right? They have this weird thing called thirst.

That regulates how much water they drink.

Yeah, totally. Who would have thought, right?

It's a great thing to ask somebody. When were you last thirsty and when were you last hungry? That's one of the great things about fasting, for example, is you, you, you get in touch with being hungry again. And that does two things. Yeah. You know what it feels like to think that you need to eat, A and B, you be, you know, hunger, sort of, for me anyway, triggers gratitude because we do have food and we have food whenever we want food, and good food at that. So you can reestablish a relationship with that sense of gratitude by fasting as well.

That is something that certainly is in alignment between the stuff that we both teach. It's interesting that your background is neurology as well. So all this, you look at the metabolism because you're also looking at the nervous system in the brain. What do we know about uric acid and lining of the nerves, myelination, neurotransmitters, things like that.

Well, we're just beginning to understand that this process that we're talking about is clearly affecting the brain. And, you know, the fact that it would should not be a surprise for people like you and me, where we've known that metabolic issues have been correlated to declining brain functionality right now and also increasing our risk for things like Alzheimer's in the future, we see strong correlations between excess body fat, high BMI and risk for Alzheimer's. Incredible correlations between even subtle elevations of blood sugar and certainly the hemoglobin A1C and dementia risk. Hypertension has been talked about as an Alzheimer's risk issue for many, many years. And that said, then it shouldn't be surprising that uric acid is related to all of those things and therefore clearly related to Alzheimer's risk. Having said that, let me go back to what is called the polyol pathway, that is the body's ability to convert glucose into fructose, because a recent. And there's several things that will do that. We talked about dehydration. Serum sodium goes up, activates an enzyme, Aldous reductase, that turns your blood sugar into fructose because it's a survival mechanism. So that happens in the brain. The brain can convert glucose into fructose and therefore lead to elevation to uric acid that will threaten mitochondrial function. Alzheimer's is a, is at its core a mitochondrial disease where the brain cells ability to make energy, which is the job of the mitochondria, declines. And these brain cells just basically stop working because they run out of the ability to use fuel. First fuel that they can't use is glucose. That's why there are studies by one gentleman in New Zealand, Matthew Phillips, putting Alzheimer's patients on a crazy diet, diet called a ketogenic diet, giving the brain cells an alternative fuel. And he's demonstrating improvement in cognitive function in patients with moderate stage Alzheimer's disease. I interviewed him on my podcast. His name is Matthew Phillips. My point being though, that the, the really seminal event seems to be a bioenergetic crisis in the brain of the Alzheimer's patient.

Yep, it's all mitochondria.

Pardon me?

It's all mitochondria. Like how good are you at computer, air and food?

And, and one recent study demonstrated that, you know, we, we think the brain is starved for glucose, but the actual glucose within the brain, but not in the cell, is as much as five fold higher. In certain parts of the, of the Alzheimer's brain. The areas that are most involved, the temporal parietal regions, the memory center called the hippocampus, there's actually a backlog of glucose. Well, where does it go? What does it do? Well, it activates this polyol pathway and gets turned into fructose. Fructose is an alarm signal. It makes uric acid. Uric acid is toxic intracellularly to the mitochondria. Why? Because it wants to slow down the metabolism in the rest of the body to conserve energy. But it's detrimental to the brain. And the initial event here is again insulin resistance. So however we get there, we're ultimately going to play this forward by, through the mechanism of fructose and then uric acid. So getting back to conversations you and I have had for years, we really need to do everything we can not to become insulin resistant, because the brain desperately depends on the function of this hormone, insulin, to allow it to get blood sugar not only into the brain, but also allow blood sugar to do what it does in brain cells. Insulin in the brain is more than just a glucose story, more than a sugar story. Insulin is actually a trophic nutri. Nutritious chemical for brain cells. It's the miracle, it's the fertilizer. If you want to grow brain cells in the petri dish, you add insulin. So we tend to lock into our notions of, oh, insulin drives the blood sugar into the cell. What's the next question? No, no, we still need to unpack insulin. It does a lot of other things in the body. It signals the body to make fat, as an example. So all this stuff's coming together. And the incredible role that uric acid is playing in insulin resistance is really breathtaking. Uric acid is the signal telling our bodies to become insulin resistant. And how it does it. One of the important mechanisms is. And I'm getting deep into the weeds, but I know that your guys are probably loving this. Uric acid, when it's elevated, shuts down the production and functionality of something called nitric oxide in the blood vessel that.

It turns out everyone in the audience knows about nitric oxide because we did a couple episodes and people just want to talk about erections just over and over. So that's got to be elevated.

Uric acid is associated with a 34% increased risk of erectile dysfunction.

There you go, guys.

See, uric acid facilitates nitric oxide. We need nitric oxide. So blood vessels, not just in the penis, but in the. That supply the heart and the kidneys and the liver and the brain. We need to supply our organs. When we can't keep nitric oxide functioning, we increase our risk. I mentioned earlier of death from stroke. 35% increased risk when uric acid is elevated. So how does Viagra work? It increases how nitric oxide is able to do its job and allow blood vessels to dilate. That's what you need for an erection. And two very large studies came out just last month demonstrating a 70% reduction in Alzheimer's risk in men who regularly use Viagra. Now, I'm not promoting Viagra as a. An anti Alzheimer's regimen. This was a study looking at medical records of more than a million men. But what I am saying is we have to keep nitric oxide working. And when we now recognize that uric acid does its dirty work by compromising nitric oxide, you darn right you want to get your uric acid levels down.

Wow. This really is the smoking gun behind almost all of the things that people are looking to reduce through biohacking, the stuff that makes you not live longer. And I'm actually experimenting with taking between a 10% and a 25% dose of sildalafil. Basically the ocean, in order to enhance nitric oxide. Activity after all the studies on Alzheimer's disease and whatnot. The reason being that when I take the normal things that people say should work like beetroot, it tends to go down the inducible NOS pathway which creates peroxy nitrite, which is highly inflammatory.

Well said. Absolutely.

Beets make you feel like shit. It's okay, don't eat them. Not to mention the other oxalic acid problem, which leads me to my next question. Oxalic acid versus uric acid and gout. Talk to me about what you know.

Well, gout is not just a disease caused by high uric acid levels. There are plenty of people walking around with with uric acid levels of 10 or 11. I spoke with somebody just yesterday, had a uric acid level that varies between 10 and 11. He does not have gout. But you know, oxalic acid and uric acid are far more relevant as it relates to kidney stones. Another issue that is seen as a consequence of having, well in conjunction with having genetic predisposition, certain SNPs as well as elevated uric acid and oxalic acid as well. There's certainly a lot of literature indicating that elevated oxalic acid can have far more wide reaching effects within the body in terms of inflammation. One thing that's commonly talked about as relates to oxalic acid is something called vulvodynia, which is basically vaginal pain sometimes to the extent that intercourse is impossible. So a low oxalate diet might be helpful for that. But I think it's important. Even as it relates back to gout, there are other factors that are involved like hydration, especially as it relates to kidney stones. I want to get back just a moment to the Viagra question or commentary or discussion.

Sure.

And that is there is a list of pharmaceuticals that are associated with pretty significant elevation of the uric acid. And unfortunately Viagra sildenafil is on that list.

Interesting.

So I was. As you tinker with things and watch your uric acid level, that might be one of the variables you should think of. And let's just for the fun of it, talk about a few others. The a couple of drugs that are used to treat high blood pressure, like the beta blockers and the water pills the diuretics are associated with are shown to raise uric acid levels. So even though you're treating your high blood pressure, you may be raising your uric acid. That may raise your blood pressure further. I wonder who might know that. I'm going to leave it at that. Aspirin, testosterone. And I think one of the biggest Players is a group of drugs that are called proton pump inhibiting drugs. These are the omeprazole type over the counter and prescription drugs, acid ppi, acid blocking drugs that Larry the Cable Guy would have everyone believe they need to take. And these are drugs taken by 15 million Americans and are associated with at least a twofold increased risk of Alzheimer's and stroke. So having said that, one of the things to consider is that these drugs increase uric acid levels. So just, you know, we, we obviously have a list of all the drugs in theophylline is another one in the book for people to look at. One other thing I will mention is xylitol, a sugar alcohol that's often found. And sorbitol would be one to avoid as well in terms of choosing an artificial sweetener if that's something somebody feels like he or she has to do.

Let's talk more about xylitol because I've been a general fan of it because of the benefits in nasal cleaning from products like clear, the reduction of cavities and even increases in bone density in women from xylitol without negative impacts on gut bacteria for most people once they get used to it. But you've got some new evidence about what xylitol does for gut for uric acid levels. Tell me about that.

So again, it is clearly associated of all of those sugar alcohols with increased gal. Sorry, increased uric acid levels. So, you know, again, I'm not dead set against it as I'm not dead set against eating liver or kidneys, whatever it may be. But it's something, you know, we've put out a lot of information and going back to the top five, the top three are fructose. So but having said that, you know, it really depends on now for everyone watching, what is your uric acid level. And I will say that for most people, determining your uric acid might be as simple as picking up your phone and calling your doctor. Because people who get annual blood work, again, it's frequently included. And unfortunately what might happen is you call your doctor, say, hey, I know I had blood work four months ago, what was my uric acid? And she will get back to you that, oh, it was normal. Please remember that that's not a good enough answer for any of you for two reasons. Number one, who wants to be normal these days? We want to be optimal. And number two, the normal so called normal levels of uric acid are derived from data that deals with gout, meaning 7 or above 7 milligrams per deciliter or above is certainly associated increased risk of gout. But it's the level in your blood above which this uric acid will start to crystallize. And understand as a, as a parenthetic here, that it'll. These crystals are observed in the, in your heart arteries and your prostate, not just in the joint of your big toe. So this is something that's going on within your body. But again, that magic number of seven is not ideal. We want to keep our uric acid levels at 5.5 or lower because it's at 5.5 that, you know, the more than 400 references that we reviewed to write this book, which are most of them in the back of the book, it's above 5.5 that we start to see a pretty steep increased risk for. You know, the things that we're worried about, the metabolic derangements that are so fundamental for us to rein in as it relates to living a long and healthy life and prosper.

This is a phenomenal body of knowledge that you shared here. And part of your book Drop Acid is something called the Love Luv Lower Uric values diet, which I wanted to run through a couple things with you there. Mostly plant based foods, but you know that grass fed meat has all sorts of benefits. We've talked about this other times.

That's why it's included.

It's included. So when you eat meat, it's grass fed and how much protein per day are we talking about?

Well, it, you know, it varies of course, on a person's body mass to start off with and their activity, are they weight training, et cetera. But if you're going to be eating meat, I would say 6 to 8 ounces would be plenty.

6 to 8 ounces a day?

Yep.

Okay.

That would be, you know, the size of maybe a deck of cards or perhaps a little bit more. More. So do I eat meat? You bet. Do I? I've seen you do it, you know. You've seen me do it. I've eaten your pigs.

Right.

And enjoyed every bite. But you know, I, I like the notion of at least one meal a day being entirely plant based. And the main reason it's not to, to stay away from meat for me, it's to make sure I'm getting enough fiber, make sure I'm getting enough of all the great things, the bioflavonoids, the vitamins and minerals that, that organic vegetables are giving me. And so it's not a question of steering away from meat, especially in recent years, it's just steering myself towards eating more and more vegetables because they're so important for, you know, just in and of themselves, but also how they're nurturing and changing the expression of, of our gut bacteria, for example.

No, I, I completely agree with your perspective there. My typical breakfast is coffee. There'll be some prebiotic fiber, so I'm getting tons more fiber than most people get just in my breakfast. And some fat, you know, mcts and, and butter and, and whatnot. And you could call that a meal. It's not raising my insulin or my blood sugar at all because there's no protein. It's not raising mtor. I imagine it's lowering, if anything, my urine acid because it's got coffee and nothing that raises it. And so that's very much in alignment with the Love Diet, I think. Right.

Yeah, I would say. And, you know, throughout the love Diet, we, you know, we have 40 recipes in the book. We feature some of our hero ingredients. For example, I mentioned earlier cherries, red onions. For example, Lee's made a almond cherry loaf yesterday that was phenomenal. And so now we're eating cherries mixed with almond flour. It was, it was really quite wonderful. That recipe's in the book, one of my favorites as well.

Wow. Okay, that sounds amazing. And the, the one area where we probably differ a little bit. In fact, I'm going to support 100% lowering not eating organ meats if you are above 7.

Right.

But the benefits of organ meats are so high for, for minerals and for unusual forms of B vitamins that are not on the standard list and all these other things. It feels like an ounce of liver for someone with levels around 5.5, who doesn't eat a lot of fructose, who doesn't drink a lot of alcohol. Probably the benefits outweigh the risks. But if your job is to lower.

Stuff, you should quit it completely. I. You. We've not found a place yet that, that we disagree because I would agree with that. And again, you know, it's a question of what does each individual's uric acid tolerate in terms of where they are. And I would say that in most people, if that's their choice, that they're going to get away with it. Again, you know, what's the average uric acid level was 3.5 in the 1920s. That was, you know, the, the development of the technology from the University of Oklahoma, Dr. Richard Marshall in 1958 for making high fructose corn syrup. That's, that was the, the nail in the coffin right there. So I, you know, I think that you and I would definitely still be on the same page, that if people want to eat a venison, organ, meats, anchovies, sardines, you know, mussels, scallops, that they're going to get away with it. And, you know, I, I, I think that, you know, you just again, have to see where you are and how these things are treating you, how the offsets are working. What are the offsets? Things like quercetin, things like luteolin. Very important.

And what does baking soda or potassium, the potassium equivalent of that, what does that do for your castle levels?

If anything, it should have no effect. I mean, one thing is that, is that you can change your uric acid excretion based upon certain inputs. We know that coffee will do it, but it's not the caffeine, for example. It's probably the bio, the polyphenols, bioflavonoids, and perhaps the caffeic acid uniquely. But generally things that may cause you to diurese or lose a lot of fluid might actually net an increase of your uric acid.

Got it. So my experiment with low dose cialis for nitric oxide could be contributing, but I don't eat enough fructose to do anything to this and I don't drink alcohol and I don't, I take about an ounce of liver a day, so that's unlikely to crank my number up that much. It's probably pharmaceutical. I do take luteolin and quercetin most days as well. Interesting.

Yeah. So you have a lot of variables here.

Okay, how long does it take? Let's say someone wants to drop by a point. Can they do that in a day? Is it in two weeks?

Is it a month? It can happen within a couple of days. Yep.

Okay.

I mean, I, I quoted one study where just five, you know, who wouldn't take quercetin anyway. But that was an 8% drop in just two weeks. By just doing that, that was the only variable, was adding in the quercetin.

Okay.

No dietary change whatsoever.

All right, final question for you, David. That has nothing to do with uric acid, I don't think. Okay, you've been working on really powerful books and just changing the way we think about these things for much longer than I have. But I know you personally and you still have this, I'm going to call it childlike curiosity. Like you get excited by stuff, you're curious about it, oh, look at this. And then you go figure it out. What do you do to maintain that level of interest and curiosity and just mental youthfulness that you have, because I see it every time I talk to you.

I don't know that I do anything to maintain it except that I cater to it. I. I just am interested in how things work, how the human body works, metabolism works, what are the underlying causes of our maladies. I. That interest comes from being a physician, and I, I've always wanted just to unravel things. And I thought your question was going to be what's next? And that's always a tough one. But I, I will say that I heard a podcast a couple of years ago when I was jogging and about uric acid metabolism that lit me up. That was that. That was it. Because it really filled a lot of empty spaces in my understanding of what, you know, of metabolism. And I think the biggest part for me was I have been fascinated my entire life since being a teenager with the fact that we have this ancient physiology, that we have a, you know, this hunter gatherer, or even before physiology, and that it's mismatched to our current environment and things. When I look at things through that lens, it's so fascinating and revealing, you know, because we, we always pigeonhole insulin resistance, bad, Excess body weight, bad, hypertension, bad. But all of that is contextual, isn't it? It's in the context of our modern world. Those were powerful survival tools that we had as humans until yesterday. So that is, I think, very exciting. But I think it's, you know, I've always been interested in how things work. It's why I. It's why I live on a boat for four months, because things are inevitably going to break and I'm going to have to fix them. And I like that.

Most of the time it's that desire to know how things work. Well, we definitely share that. I was pretty sure that you were going to say you kept your enthusiasm because you drop acid, but you didn't.

I didn't deny it either, though.

Oh, fair point. And I'm not going to. I'm not going to ask because you probably wouldn't be able to answer, but I do appreciate your work in the world, Dr. Perlmutter. Thank you for your new book, Drop Acid. You're bringing some really serious, important knowledge about core metabolism with a cheap and easy to follow biomarker and some clear recommendations. Don't eat fructose. There you go. See you next time on the Human Upgrade podcast.

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