In this engaging interview, Dr. Jill Carnahan sits down with neurology luminary Dr. David Perlmutter to discuss the new science of uric acid and why it's crucial to your overall health. As a leading expert in functional and integrative medicine, Dr. Perlmutter sheds light on the latest research surrounding uric acid and its effects on the body.
- High uric acid leads to more risk of obesity, diabetes and hypertension
- Lower your Uric acid level by decreasing consumption of processed sources of fructose and high fructose corn syrup
- Improve your metabolism by checking your uric acid level. It should be less than 5.5
The Guest – Dr. David Perlmutter
Dr. Perlmutter is a Board-Certified Neurologist and six-time New York Times bestselling author. He serves on the Board of Directors and is a Fellow of the American College of Nutrition.
Dr. Perlmutter received his M.D. degree from the University of Miami School of Medicine where he was awarded the Leonard G. Rowntree Research Award. He serves as a member of the Editorial Board for the Journal of Alzheimer’s Disease and has published extensively in peer-reviewed scientific journals including Archives of Neurology, Neurosurgery, and The Journal of Applied Nutrition. In addition, he is a frequent lecturer at symposia sponsored by institutions such as the World Bank and IMF, Columbia University, Scripps Institute, New York University, and Harvard University, and serves as an Associate Professor at the University of Miami Miller School of Medicine.
Dr. Perlmutter is the recipient of numerous awards, including: the Linus Pauling Award for his innovative approaches to neurological disorders; the National Nutritional Foods Association Clinician of the Year Award, the Humanitarian of the Year Award from the American College of Nutrition, and most recently the 2019 Global Leadership Award from the Integrative Healthcare Symposium.
Dr. Jill Carnahan is Your Functional Medicine Expert® dually board certified in Family Medicine for ten years and in Integrative Holistic Medicine since 2015. She is the Medical Director of Flatiron Functional Medicine, a widely sought-after practice with a broad range of clinical services including functional medical protocols, nutritional consultations, chiropractic therapy, naturopathic medicine, acupuncture, and massage therapy. As a survivor of breast cancer, Crohn’s disease, and toxic mold illness she brings a unique perspective to treating patients in the midst of complex and chronic illness. Her clinic specializes in searching for the underlying triggers that contribute to illness through cutting-edge lab testing and tailoring the intervention to specific needs.
A popular inspirational speaker and prolific writer, she shares her knowledge of hope, health, and healing live on stage and through newsletters, articles, books, and social media posts! People relate to Dr. Jill’s science-backed opinions delivered with authenticity, love and humor. She is known for inspiring her audience to thrive even in the midst of difficulties.
Featured in Shape Magazine, Parade, Forbes, MindBodyGreen, First for Women, Townsend Newsletter, and The Huffington Post as well as seen on NBC News and Health segments with Joan Lunden, Dr. Jill is a media must-have. Her YouTube channel and podcast features live interviews with the healthcare world’s most respected names.
Dr. Jill 0:12
Well, good morning, everyone. Welcome to another episode of Dr. Jill Live. I am here this morning with an esteemed colleague and dear friend, Dr. David Perlmutter. I am just honored and delighted to have him with us today for a bit of time to talk about his new book and so many of the things that he's brought to light.
Dr. Jill 0:34
We were just talking about his many New York Times bestsellers and what it takes to make a great book, and he has really mastered this. He's just writing content that's changing lives. And I think one of the things you just mentioned, Dr. Perlmutter, is this content that people are really looking for but are not finding elsewhere. And I thought uric acid was such a great example of that because no one's talking about it. Yet, as we dive in today, it's such a critical part of health, and I'm so glad that you wrote that book and so many others. So let me introduce you, and then we'll dive in with our discussion today.
Dr. Jill 1:08
Dr. David Perlmutter is a Board-Certified Neurologist. A six-time New York Times best-selling author. He serves on the Board of Directors and is a Fellow of the American College of Nutrition. Dr. Perlmutter received his MD degree from the University of Miami School of Medicine, where he was awarded the Leonard Rowntree Research Award. He serves as a member of the editorial board for the Journal of Alzheimer's Disease and has published extensively in peer-reviewed scientific journals, including the Archives of Neurology, Neuroscience, and the Journal of Applied Nutrition. In addition, he's a frequent lecturer at symposia sponsored by institutions such as the World Bank, IMF, Columbia University, Scripps Institute, New York University, and Harvard University. And he serves as an associate professor at the University of Miami Miller School of Medicine.
Dr. Jill 1:50
Dr. Perlmutter is a recipient of numerous awards, including the Linus Pauling Award, which is an amazing award with one of our dear IFM groups, for his innovative approaches to neurological disorders, the National Nutrition Foods Association Clinician of the Year Award, and the Humanitarian of the Year Award from the American College of Nutrition. And most recently, the 2019 Global Leadership Award from the Integrative Healthcare Symposium, which is so well deserved, Dr. Perlmutter.
Dr. Jill 2:20
Welcome, welcome today. Thanks for taking the time to join us.
Dr. David Perlmutter 2:22
I'm delighted to be with you, Dr. Jill. Thank you for having me.
Dr. Jill 2:25
You're welcome! Now, I want to dive into uric acid, but before we do, I want to frame the stage so people will get to know… If they don't know you, I can't imagine them not knowing you. But tell us a little bit about: How did you get into medicine? And then how did you get into this?—what I consider the really life-changing part of medicine, which is getting people to change [their] behavior and do the root cause analysis?
Dr. David Perlmutter 2:46
You can be sure I've been asked that question before. But as you asked it today—I was just thinking—I think the main thing that propelled me into medicine aside from the fact that there was a bit of a legacy thing going on with my father, which is a good thing, I guess, was curiosity. I mean, it's really an area where you can try to solve problems and come up with novel ideas. I guess you can do that as an engineer. You can do it as a lawyer. That's for sure. But it just seemed that in trying to solve problems in medicine, not only did you get the satisfaction of solving them, but somebody else would benefit from that as well. So it seemed like a good plan.
Dr. David Perlmutter 3:26
Neurology attracted me. Again, a bit of a legacy; my dad was a brain surgeon. Also, I found that in medical school, it was the one thing people really didn't want to pursue. They just said it was too hard. They said: “We didn't like neuroscience; we didn't like neuroanatomy.” So that was very attractive to me. Then I came out and practiced mainstream neurology for about 10 years and became a bit frustrated, let's be fair, because I wasn't really helping people get through their problems; I was helping them just manage their problems. I wasn't helping them get some finality about fixing things, but just how to manage it. We were sort of treating symptoms while ignoring the underlying problem. I began to develop a real interest in: Why in the heck are these people here in the first place? Why are their brains declining? What's going on? And that led me to an exploration as to the cause of things like Alzheimer's, Parkinson's, MS, and a litany of metabolic issues that we look at in the brain.
Dr. David Perlmutter 4:38
You'll notice I just said metabolic issues. The discovery was that Alzheimer's is really a metabolic problem. It's a problem with how the brain is able to do metabolism—how it's able to use fuel and create energy. It's not that it's an accumulation of some toxic protein that we're all led to believe is the cause of Alzheimer's. Mainstream journals do not subscribe to that. It was kind of on the fringe for so many years [for those] who thought that maybe there was something beyond beta-amyloid. But now it's even the Journal of the American Medical Association saying that metabolism is front and center and what we need to be focused on in terms of Alzheimer's. Why that's really good and why that played into my hands is because our metabolism is something we can control. So finally, a leverage tool, a way of fixing metabolism and therefore doing good things for the brain.
Dr. David Perlmutter 5:36
Years ago, in 2013, I wrote a book called Grain Brain that looked at the effect of sugar damaging the metabolism and how that's threatening to the brain. And then, as you brought up, more recently, I've been really deeply involved in the science of something called uric acid. Uric acid is something that you and I learned about only in the context of gout and kidney stones. It turns out that there's a big story to tell as it relates to uric acid and a dramatic issue as it relates to disturbing metabolism. And therefore, it has a huge role to play in things like diabetes, hypertension, dyslipidemia, Alzheimer's, and heart disease. All the big players are absolutely impacted by the elevation of uric acid.
Dr. David Perlmutter 6:22
It's not just that you're going to get a gouty toe. It's going to affect how insulin works in your body. It's going to raise your blood sugar if it's elevated. It's going to raise your blood pressure. All those things that you and I are working day and night to try to control are highly influenced by uric acid. When I began to appreciate that literature, it was very profound for me because it became a new tool in the toolbox. It's not the only tool, that's for sure. It's not the only game in town, that's for sure. But it's very, very important. And I think you would agree that many of our colleagues are now looking at uric acid with a bit more open mind and doing their best to bring it under control for the very reasons that I just mentioned.
Dr. Jill 7:07
Yes. I want to dive into that. I want to mention something that you said that I think is so profound and important. I asked you: Why did you do what you did? You mentioned curiosity. In researching for my book, one of the things I found over and over again was that curiosity is one of the marks of genius because that—
Dr. David Perlmutter 7:22
Oh, wow. I'm not going to claim that.
Dr. Jill 7:24
No. I want to honor you with that because I see that in many people like yourself who've really done life-changing work. It's that in medical school, we're not really taught to ask the question, ‘Why?' or to go deeper. It's the maybe 10% or 5% that go on in different fields, whether it's functional medicine or other medicine, or even research, that say: “Well, why? Why is this happening?” Those are the people who are making the change, and you're one of them. And it really is a mark of genius because when we ask those questions and we get curious, that's how—whether serendipitously or just diving into the literature—we find: “Oh, this links to this links to this, and this makes sense.” Like you said, we're taught about gout, but—
Dr. David Perlmutter 8:00
Totally. It's that you need that little piece of the puzzle that has a little blue sky in the corner and fits in somewhere. And when you finally put those into the puzzle and the dots are connected, you sleep a little bit easier because I'm the kind of guy who'll wake up at night and say: “Well, why would fructose consumption relate to hypertension?” [Back] in the day, we could speculate. But now we're able to connect those dots quite handily. Why does eating a lot of dietary salt make you fat? How could that be? It's true; it is associated with it. Is it causal? We suspect so. But now we know. Now we have the mechanism. We've unpacked it, and it makes life a little bit easier when those dots are connected.
Dr. Jill 8:43
It does. It makes it more fun. Doesn't it just give you back the joy of what you do, whether it's writing, researching, teaching, or seeing patients? To me, it's like the joy of really practicing medicine is actually discovery. So thank you for your work there.
Dr. Jill 8:57
So uric acid—my history with uric acid—I do remember years ago realizing fructose was connected. I would put people on a low-fructose diet, and they would get better, and their gout would get better. For people who've never heard of this—I have a lay-person audience and a lot of practitioners too, so you can get technical—[concerning] uric acid, give us a framework. What is it? What does it do in the body? And then why does fructose drive it and other things?
Dr. David Perlmutter 9:19
Well, let me just begin by saying that what you just said was very profound and a bit iconoclastic. What? You said that you would have patients with high uric acid, and immediately you would put them on a low-fructose diet. If you visit the mainstream big-name clinics' websites and look at the dietary recommendations, even today, to lower uric acid, you barely see fructose getting any mention. Why? Because they're more inclined to talk about things called purines, which you'd get by eating a lot of meat, for example—high purine foods. And to a lesser extent, they would talk about alcohol. But the real issue is fructose. Fructose is directly metabolized to uric acid. Why do mainstream, big-shot clinics not mention sugar? I will have to leave it to your audience to speculate about it. But they don't. That's the big issue. Yes, purines are important. Organ meats—liver, for example—are a big culprit. Alcohol is significant as well—a big player today.
Dr. David Perlmutter 10:24
The reason that uric acid levels have doubled since the 1920s is that uric acid levels have been in lockstep with our increase in fructose consumption, which gradually increased until about the 1970s, at which point it exploded. That was because of the introduction of what's called high fructose corn syrup into the manufacturing of food. I have difficulty even saying those words, “the manufacturing of food.” Food, to me, shouldn't be manufactured.
Dr. David Perlmutter 10:52
But nonetheless, the development in 1957, I think it was, of the technology to make fructose out of corn at Oklahoma State University was really kind of a breakthrough because it allowed the production of a sweetener—in this case, fructose—that is cheaper than table sugar and also far sweeter. So the more fructose you use, the less it costs. That's why high fructose corn syrup has made its way into every product from A to Z these days. Seventy percent of packaged foods in American grocery stores have added sweeteners, much of which comes from this notion of high fructose corn syrup.
Dr. David Perlmutter 11:40
When fructose is metabolized in the body, it becomes uric acid. And I want to spend a moment, if I may, because I think the story of how and why the teleological approach to this is really interesting. Fructose, traditionally in our hunter-gatherer forebears and even before that, in primates, is a signal that winter is coming. Fructose is when you are eating ripened fruit, [like] the blueberries you might find when you're hunting and gathering, or whatever that fruit may be. It's telling your body that winter is coming. It's telling your body that there is going to be stress in terms of not having enough food. It signals the body to make fat, and how it signals the body to make fat is a beautiful process.
Dr. David Perlmutter 12:30
It does so by creating a very strange chemical called uric acid. Uric acid is the survival chemical that tells your body to ratchet down its energy use to increase its sugar—glucose—production to power the brain to increase its storage and manufacturing of fat and reduce its burning of fat. All the things that we would not want to do today. But this is a powerful survival mechanism that allowed our hunter-gatherer ancestors, not that they got fat, but to make a little bit more body fat in the late summer and in the early fall when fruit would be ripe, and that allowed them to survive the winter. Those who had a better way of doing that—in other words, their uric acid levels were a little bit higher—would survive and ostensibly reproduce. So it was a selection process that actually selected out those who had higher uric acid levels.
Dr. David Perlmutter 13:33
It turns out that that selection process began about seven to eight million years ago with our primate ancestors. And we had, prior to that, an enzyme called uricase that would break down uric acid and keep uric acid levels low. But when the earth cooled during the middle Miocene period, food for our primate ancestors was scarce. The ones that survived had a change in their uricase genes, such that they lost the ability to break down uric acid. Their uric acid levels went up, and they consumed whatever little bit of fructose was around.
Dr. David Perlmutter 14:13
They made a little bit more body fat. They made a little bit more blood sugar. It raised their blood pressure a little bit as a hedge against dehydration, and they survived to give Dr. Jill and me, and everyone watching this, higher levels of uric acid. So in the context of our ancestors—making them a little bit diabetic, a little bit hypertensive, and a little fatter—it was great when they had a little bit of fructose in their diet.
Dr. David Perlmutter 14:42
Now, this evolutionary advantage that you and I carry is confronted with massive, massive amounts of fructose, which have increased fivefold since the 1920s. And we're just raising uric acid levels, telling our bodies to prepare for winter—make fat, store fat, raise the blood pressure, raise the blood sugar—all the things that relate to our metabolic status that we're desperately trying to avoid. And the mediator, the signal—the survival signal, if you will—is uric acid. That's why we've got to do everything to bring it under control. It's doing its best to keep us alive, but it's locked in the on position, and we've got to change that.
Dr. Jill 15:28
It makes so much sense. And I suspect that corn growers in the US were very happy. There's probably another political motivation behind what the switch was with… Again, I don't want to speculate; you probably know from your research all the details. But often these things aren't motivated by pure health reasons, whether it's the food pyramid or all these things are… So I don't want to get deep into that, but I just want to say, because some people are like, “Well, why did that happen?” or whatever. It makes perfect sense, a little bit, [given] the politics behind using a cheaper subsidiary from corn. Was it mostly from US corn products?
Dr. David Perlmutter 16:05
Yes. Hey. I mean, if you're a corn grower, the development of that technology to make sugar out of corn [came] at a time when we had been getting sugar from Cuba. Now we [have] shut off our relationship with Cuba. We grow some sugarcane in Florida. But now the whole Midwest gets open to our sugar addiction. And Bingo, everybody's happy. And, you know, it continues to this day. On February of '21, the USDA published its 5-year dietary recommendation for Americans. In that, they said that 10% of your daily calories as an American adult coming from sugar, [is] totally fine—all good.
Dr. Jill 16:48
Dr. David Perlmutter 16:49
None of their scientists agreed to or supported that. Yet that's what the United States Department of Agriculture (What is their mission? Their mission is to help farmers.) came out with and said 10%. So we wrote a letter in MedPage Today. It was actually an open letter to President Biden, [basically] saying: Let's follow the science; no more than 5% of calories should come from sugar; let's change this messaging. And nothing happened, but at least we stood up and—
Dr. Jill 17:20
At least you wrote. Good for you. And I have a very interesting background because I grew up on a farm in central Illinois, where my father and my brother still grow corn and soybeans to this day. Now, because of my own life, trajectory, and passion, they've done a lot of things right. They've changed over to all non-GMO and mostly organic, and they're certainly not producing corn syrup out of their corn. But it is fascinating to come from that side of it and see the agricultural [progress].
Dr. Jill 17:43
I obviously know my dad talked about subsidiaries growing up, and so I know how this stuff works to help my dad and my family survive, but on the other hand, even in farming, we have to shift the practices. And I love that we're talking about this because Jeff Bland and I love to talk about how autoimmunity does not begin in the gut but in the soil. Agriculture actually matters because the production of what we're producing/manufacturing, like you said with our foods, is really creating a more metabolically dysfunctional society. So thanks for going there with me because it's important.
Dr. Jill (pre-recording) 18:15
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Dr. David Perlmutter 19:11
Yes, and you're exactly right. I mean, we talk about lifespan declining—for the first time since records have been kept—over the past 5 years quite significantly. And let's be clear: This began pre-COVID. I mean, COVID really accelerated that situation, but it began pre-COVID when, for the first time, younger generations were expected to live less than their parents. Wow! And we didn't change genetically; we changed environmentally. And there's such a profound relationship between our environment—it means everything around us, including our foods, our sleep, and all the things that we can choose—and our genetics. How they interplay is so important. We have turned the tables on our gift, on our genome, in a very, very threatening way, and we're seeing the health consequences that are derived from that. So you are correct.
Dr. David Perlmutter 20:05
And as it relates to uric acid, what a powerful—when it's elevated—threat to metabolic health! I mean, one study that came out in 2009 in the journal Arthritis and Rheumatism followed 90,000 people—I think 42,000 men and 48,000 women—for eight years. It noted that in the individuals whose uric acid levels were above 7, which is incredibly common, those individuals had a 15% increased risk of what is called all-cause mortality. That basically means dying from any cause. They had a 39% increased risk of what we call cardiovascular mortality, or dying of heart disease; 40% increased risk of dying of heart disease. We had a 35% increased risk of death from ischemic stroke. And interestingly, for every point of uric acid elevation over 7—which again is very, very common—there was an 8% to 13% increased risk of death from any cause whatsoever.
Dr. David Perlmutter 21:12
So when you go to the doctor and have your uric acid level done, she or he will tell you, “Well, it's 6.8, so you're fine because you're now in the normal range.” Well, it turns out that cardiovascular risk begins at 5.5 and that the 7.0 milligrams per deciliter level above which you're at risk and below which everything's fine is really only derived in the context of gout. Now that we have so much more understanding about uric acid, we realize that the safer level is having the uric acid level at 5.5 or below.
Dr. David Perlmutter 21:52
And the thing is, people have their uric acid levels done probably every year as part of their metabolic panel. So for anybody watching this, what you need to do, simply, might be to call your doctor's office to say, “BTW, when I had my blood work done last,” whatever, “what was my acid level?” And if it was above 5.5, then you need to begin thinking about what you can do to lower it because elevation of uric acid is strongly related to things like diabetes, high blood pressure, and weight gain, among many others. But, you know, when I said those three, I think we checked a lot of boxes for people.
Dr. Jill 22:30
Yes. Good. So if you haven't asked your doctor to check your acid, or if you have uric acid, you want it below 5.5. Let's shift. We talked a little bit about high fructose corn syrup, but what are some of the common sources? I mean, as you and I know, this is in a lot of processed foods. But for those who maybe know or aren't reading labels, where would people be getting hidden sources of fructose?
Dr. David Perlmutter 22:50
Good question. And it doesn't have to be high-fructose corn syrup. But there's one aside that I just feel compelled to talk about. I think the highest source of fructose, the most threatening food of all, if you want to call it food, is this agave nectar. It is about the worst food ever created. I guess the stuff with artificial colors and sweeteners that kids are eating as well. And it's at the health food store when you buy a coffee or a tea. “Oh, would you like… “
“I don't want sugar, no. I want agave nectar.” About the worst food that you could imagine. It could be 70% pure fructose. About the last thing in the world that you would ever want to consume.
Dr. David Perlmutter 23:31
But fructose—the name comes from fruit sugar: Fructose. And there is fructose in apples and in basically any fruit and some vegetables, for sure. But not a whole heck of a lot. Even a good-sized apple is going to have about 5 grams of sugar—not all of which is fructose, I might add—and you can handle that. Not only is it not much sugar, but you're also getting it delivered over a longer period of time. You're not drinking it, and it's packaged along with fiber that helps to slow its absorption as well as vitamin C that helps to enhance the excretion of uric acid.
Dr. David Perlmutter 24:11
So have the apple a day; keep the doctor away. Fine with me. But 36 grams of sugar in a 16-ounce Coke or a 16-ounce glass of orange juice or apple juice overwhelms the small intestine and then sends fructose to the liver, and that's when the problems begin. That's when the liver becomes more fat-containing. That's when uric acid is turned on, thinking that this is our last chance to make us fat and raise blood sugar and blood pressure, and it goes into overdrive.
Dr. David Perlmutter 24:45
Incredibly, unlike almost any mechanism you can think of in the human body, uric acid enhances its own production. Normally, in the body, when something is produced, there's a feedback mechanism to turn it off, right?—homeostasis. But uric acid actually increases its own production as a survival mechanism. So the fruit drinks, for example, that we want to give to our children right off the bat and that they're drinking after formula or breast milk—they're having apple juice and orange juice—do a lot of bad things. First of all, it gets them really liking sweet like a treat. The next thing it's doing is stimulating uric acid production, simulating activation of their survival pathways, and making them fatter and more inclined to be diabetic. So we've got to stop that.
Dr. Jill 25:38
Yes. And you see the studies, even the “skinny fat,” right? I mean, obesity is part of this, but the metabolic dysfunction that we're creating in our young people… And I love that you differentiated food, which has fiber added and often slows the absorption of fructose, between fruit-sweetened, high fructose corn-sweetened, or agave-sweetened drinks. Drinks are a much bigger player in this than real food or real fruit. It's so interesting. Did you come across in your research any connection between the gut microbiome and fructose and uric acid? Is there anything connected there? Because it feels like that's always—
Dr. David Perlmutter 26:15
As you would expect, right? Higher levels of dietary fructose actually enhance things in the gut that also pave the way for higher levels of uric acid. As a matter of fact, there are a couple of reports now in the literature, believe it or not, demonstrating improvement in gout—which is generally a situation of high uric acid—by doing what's called a fecal microbial transplant. In other words, giving people different gut bacteria that have been derived from a person without gout—a healthier individual. So we know that there is a very powerful relationship and that uric acid can change the gut bacteria. That can actually increase inflammation. So, as you would expect, a very profound relationship.
Dr. Jill 27:07
That makes sense because I'm thinking about maltose, fructose, and some of these sugars that are disaccharides. They are typically in the FODMAP category, which are things that feed the small bowel overgrowth, which can cause a whole other set of issues. I can't tell you off the top of my head if that's directly connected, like SIBO and the consumption of fructose. But it makes sense that it would alter the gut microbiome. And the gut microbiome has to do with everything, as the research comes out.
Dr. Jill 27:33
One thing you mentioned too that I think is important for those listening is that fatty liver is at an all-time high. And clearly, the dumpage of these sugars directly into the liver, which is our filter for the blood after it comes from the gut, is a piece of the puzzle. Did you find pretty high associations between fatty liver disease and fructose and uric acid?
Dr. David Perlmutter 27:52
Yes. I mean, the association between fructose consumption and this NAFLD—non-alcoholic fatty liver disease—has been described for many, many years. Now we understand that uric acid plays a really central role in how that all comes about. Similarly, the other big metabolic issue of the day is insulin resistance, slash, ultimately becoming diabetic. And we know that there are very well-defined mechanisms whereby fructose becoming uric acid can lead to insulin resistance and compromise how insulin works in the body. Interestingly, it works through a mechanism that involves something called nitric oxide.
Dr. David Perlmutter 28:35
Nitric oxide is a gas but acts as a very fundamental signaling molecule in the body that does two really important things, among others. First, it allows blood vessels to open up and relax. That would reduce blood pressure. Second, nitric oxide is fundamentally important for the function of insulin. Who knew? When you compromise the function of nitric oxide, insulin doesn't do its job, blood sugar goes up, and you become insulin resistant and ultimately diabetic, increasing your risk for Alzheimer's by about fourfold. So this then connects a lot of dots now—doesn't it?—between simply consuming fructose and the risk of developing a condition for which there is no treatment called Alzheimer's disease, all through, or at least including to a significant degree, this nitric oxide mechanism.
Dr. David Perlmutter 29:32
People talk about nitric oxide: “We need it to keep our blood vessels open and keep our blood pressure under control.” The story about nitric oxide and insulin functionality is a relatively newer understanding. But it now explains why people who consume higher levels of fructose, which has no direct effect on insulin… It's not metabolized using insulin, unlike glucose. But if you consume fructose, because it becomes uric acid, which turns off nitric oxide, it then turns off the function of insulin. So that explains why, even though fructose doesn't immediately affect insulin, it is strongly associated with diabetes risk—profoundly related. It's through this uric acid mechanism.
Dr. David Perlmutter 30:19
So getting back to your original question, it's really about cutting back on fructose and reading labels. By all means, high fructose corn syrup is something to avoid. You're going to get some sugar if you eat fruit, and that's going to be fine. And other foods contain things called purines. Purines are the breakdown products of DNA and RNA. When you eat food that is made of cells, which is typically most foods, you're going to break down DNA and RNA in the cells. They form purines. They are contributing to the uric acid pool. So you want to be careful with certain things, like very cellular foods like yeast, liver, and other organ meats, for example.
Dr. David Perlmutter 31:04
And finally, I will mention that alcohol consumption is related to the elevation of uric acid, but it really depends on the type of alcohol one consumes. It turns out, when looking at a large study of food frequency analysis, that women who consume moderate amounts of wine actually have lower uric acid. Why? When we talk about alcohol, we have to talk about the context. Wine has wonderful bioflavonoids that are associated with a reduction of uric acid. So on balance, women more than men who consume wine actually have lower uric acid [levels].
Dr. David Perlmutter 31:41
The worst player of all is beer. Beer not only contains alcohol but [also] contains lots and lots of purines that come from the brewer's yeast. That then allows us to understand where the beer belly comes from because you're turning on uric acid production. You're telling the body [to] make fat because winter is coming. So in Japan now, they're very, very dialed into the whole uric acid understanding. They're now marketing purine-free beer based on this understanding. Can you imagine?
Dr. Jill 32:14
Amazing. Just like sulfate-free wine and all these other things. We're [inaudible]. It's interesting—again, sometimes my brain will go on tangents—biogenic amines are one of the sources of histamine. And there's a whole other class of people who have histamine intolerance, unrelated to uric acid. But in my mind, it's interesting because some of those same foods that contain amines—for my population, they have mast cell activation and histamine issues—are probably going to be similar. And you mentioned yeast. So the fermentation or aging of food creates more of the amines that create purines as well? Or is there any connection to fermented [food], or not necessarily?
Dr. David Perlmutter 32:50
No. I mean, the notion of fermentation is really one in which sugar is basically utilized. During the fermentation process, we're creating other downstream products and basically taking sugar out of the equation. And the fact is, what you're doing is allowing the bacteria to replicate, and that ultimately is typically based on how foods are fermenting.
Dr. David Perlmutter 33:19
Not just today, but I mean, I think traditionally, we didn't always have fresh food. We had to eat whatever we could hunt or gather. And the gathering part meant we were starving. We were eating a lot of food that was rotting on the ground, and interestingly, in that process, alcohol is produced. And as an evolutionary advantage, humans developed the ability to break down alcohol. We actually developed a couple of enzymes that allowed us humans to break down alcohol and be much less threatened by the consumption of alcohol in those fermenting foods that we would then find. That was an evolutionary advantage.
Dr. Jill 34:01
Interesting. It makes me think of a funny little side story. I just read on the news not too long ago that a lady was stuck in her car in a snowstorm for 72 hours, and she had a packet of ketchup and a bottle of wine. Maybe it was longer than that. I thought, “How interesting to survive on ketchup and wine.” But she did it.
Dr. David Perlmutter 34:17
Well, yes, she did it. And you think of what people are generally consuming these days. I mean, ketchup qualifies as a vegetable in terms of the federal school lunch program.
Dr. Jill 34:01
Dr. David Perlmutter 34:25
And there's plenty of alcohol to go around.
Dr. Jill 34:26
And high fructose corn syrup is typically in… So you are a neurologist. You've written so many books about the brain. In a moment, I want to talk about Grain Brain and uric acid, Drop Acid, your new book, and diet. Like, what's the big picture? But before we do, I want to highlight what you said about Alzheimer's and the connection because not everybody makes that connection between uric acid, high fructose corn syrup, and these things and Alzheimer's. But as you mentioned, we often call it type 3 diabetes. There's this very metabolic connection with the brain. Do you want to briefly explain for the layperson how your insulin resistance and your prediabetes are connected to the brain?—because it's so important.
Dr. David Perlmutter 35:06
I will. I mean, we are being bombarded day in and day out by messages telling us that Alzheimer's is caused by the accumulation of a particular protein called beta-amyloid. And there's this effort to convince us that that's the cause, and therefore, if we can rid the brain of that misfolded protein, all will be well. Well, there are drugs that reduce beta-amyloid formation. There are drugs that actually help eliminate beta-amyloid. They're not working. They're not demonstrating any, any clinical improvement in these patients whatsoever. It's typical, though, that we are messaged to think about diseases having a single cause because that paves the way for a single drug remedy that will be the blockbuster that the drug companies want it to be.
Dr. David Perlmutter 35:58
More recently, we've been told about a new beta-amyloid drug. But the dirty little secret that we weren't told and wasn't disclosed and that came out about three weeks ago was the idea… Actually, some Australian researchers looked through the data that the researchers who got the drug approved had actually collected, which shows that these drugs are associated with significant shrinkage of the human brain. Not a good thing. Not anything that we would want. But the point is that there's a lot more going on in the brain that's been talked about for a lot longer than simply this accumulation of beta-amyloid.
Dr. David Perlmutter 36:36
The beta-amyloid accumulation is the downstream manifestation of what's going on upstream, which is a metabolic issue in the brain. Desmond Tutu once said that it's important to pull people out of the river, but equally, if not more important, to find out why they're falling in in the first place. So while it's great to think we're going to ultimately develop a drug treatment for Alzheimer's, I think we have to ask ourselves: “Why are people falling into that river in the first place?” And let's be clear: It's because of their metabolic dysfunction.
Dr. David Perlmutter 37:08
If you become a type 2 diabetic, you've increased your risk for this untreatable condition called Alzheimer's by as much as fourfold. An editorial appearing in the Journal of the American Medical Association in 2020 really hit home by saying it's time that we focus on the metabolic issues related to Alzheimer's disease and back down on this whole notion that it's caused by the accumulation of beta-amyloid. And still, unfortunately, that is the central core of the messaging that people are hearing on the news. There's another amyloid drug being developed, and it's heart wrenching because people are left with the idea that they have no control over their brain's destiny, and nothing could be further from the truth. I'm not going to say we have absolute control, but we have a heck of a lot of control in terms of the destiny of our brains.
Dr. David Perlmutter 38:07
One study that came out of England in January of this year followed 79,000 individuals for 10 years and looked at six lifestyle variables, including—I hope I get them all—exercise, cigarette smoking, diet, social connectedness, cognitive connectedness, and alcohol consumption. What they found was that the more right choices that people made in those regards, the better their cognitive outcome over this 10-year period of time, even as it relates to people carrying the so-called Alzheimer's gene. Or we call it the APOE4 allele, which represents between 20 and 28% of Americans. Those who did the right things had a dramatic reduction in the risk of cognitive decline. The point is that our lifestyle choices are front and center as the most important tool that we have for preserving our brain function, staying out of the river, as it were, and not having to hope that there's going to be a cure.
Dr. David Perlmutter 39:22
You know, the movie director James Cameron said that ‘hope is not a strategy.' And what I'm offering up, and uric acid is certainly part of that equation, is a meaningful strategy—a proven strategy to improve your odds of keeping your brain in a good place, maybe until such time as the pharmaceutical industry can come up with something. I'm all in favor. I'm not derogating them at all. But for now, we know what can help, and that's what this is all about.
Dr. Jill 39:54
Yes. Brilliant. These complex metabolic things never have… We were taught in medical school that there's one solution, one drug. And it just isn't that way in the complex metabolic ecosystem that's internal. There are so many factors. And I love that you talk about the control.
Dr. Jill 40:08
So let's kind of wrap this up with the diet. Obviously, with this uric acid information, we just talked about fructose, but it's bigger than that as far as: What is the ideal? There maybe isn't one size fits all. But what are the general recommendations around diet, including your previous research on Grain Brain? And give us some outline of what a typical human should be eating.
Dr. David Perlmutter 40:34
Again, this is all related to the relationship between our evolution and our environment. In other words, how are our day-to-day choices being interpreted by our physiology, which is coded for by our genes? I think that once we understand how uric acid signals the body to prepare for winter, we can make the right dietary choices that will help reduce that signaling. And it means reducing alcohol consumption. If you do consume alcohol, wine is probably your best bet. Being careful of the purines that you consume, the organ meats, and the small fish that are very cellular, like sardines and anchovies, though we love them. Have them. I won't eat liver because I can't stand it, but I certainly want anchovies on my Caesar salad. I just love that. But be careful. But the big player is obviously fructose.
Dr. David Perlmutter 41:28
I think job one, though, is to figure out what the heck your uric acid level is. And, as I mentioned, that's a blood test. I have a home test kit right here, oddly enough. So you can do a strip and learn what your uric acid level is. My last one was—what does that say?—4.7, I think. I don't know if you can see that. It's kind of reflected. My last level was 4.7. So I'm where I need to be, and that's good to know. It's a new tool in the toolbox. It's not the only tool. We've got to know our insulin levels. We've got to know our fasting blood sugars. We've got to know our lipid profiles, our homocysteine, and so many more things. That's for sure. But this is right up there with blood sugar, blood pressure, and the percentage of body fat. This is a big deal. And I think many, many more people are going to be talking about it.
Dr. David Perlmutter 42:23
So it's not just the foods; even supplements can have a big role to play, like quercetin, for example. Quercetin works to target the main enzyme that makes uric acid, which is called xanthine oxidase. That won't be on the quiz. But that's how the drugs work to lower uric acid and gout. Allopurinol works by targeting that enzyme. Quercetin that you can buy at the health food store—same thing. So there are various foods that are rich in these bioflavonoids that we can eat, like cherries, for example.
Dr. Jill 42:54
Yes. So tart cherries are obviously the big one out there. Quercetin. Anything else as far as supplements? Is vitamin C up there as far as one of the…
Dr. David Perlmutter 43:03
Vitamin C is important because it aids in our excretion. Another bioflavonoid is luteolin—100 milligrams per day. Quercetin would be about 500 milligrams per day. Luteolin is found in red onions, but you can buy it as a supplement at 100 milligrams per day. Check with your healthcare provider, of course. I like chlorella as it relates to this fatty liver issue. That's been shown clinically to be helpful in that regard. Then, to round it out—vitamin C, of course—I would add DHA. I don't think in this lifetime I'm going to give any supplement recommendations that are not going to include this omega-3 called DHA, at least 500 milligrams per day, but probably closer to 1,000.
Dr. Jill 43:50
Fantastic. All really good stuff. I always joke about desert island vitamins. If you had just two or three things, what would you take to a desert island? It's hard to wean it down, but I agree that the DHA part of the fish oil, typically EPA and DHA, is so powerful for the brain and is preferred.
Dr. David Perlmutter 44:02
Dr. Jill 44:05
Amazing. Any last takeaway that you want to leave the audience with as far as pulling it all together?
Dr. David Perlmutter 44:12
Sure. I think the message from me to you today is that we are the architects of our brain's destiny, and our choices are incredibly important—the choices that we make today—in a world where we don't have any other alternative. There is no pharmaceutical intervention that can help your brain. Again, what you're hearing from me is that I would welcome it. Believe me. I'd use it with patients. I would give it to my own father, who tragically died of Alzheimer's as well.
Dr. David Perlmutter 44:45
That said, we can do things on the front end. John Kennedy said that the time to fix the roof is when the sun is shining. And hopefully, for all your viewers, the sun is shining right now; it's time to get busy. It's not dramatically difficult to make these lifestyle changes. Knowing you, your followers are probably well on their way already. So just a little bit of fine-tuning [is needed]. And by all means, get the level checked and learn more about it in the book as well.
Dr. Jill 45:15
Yes. And where would you send them to get your book? Drop Acid is the title of your latest book.
Dr. David Perlmutter 45:20
Drop Acid—no one is going to forget that title. It's available everywhere—Amazon, you know. They can learn about me at DrPerlmutter.com. But the book is available in anything online and retail as well.
Dr. Jill 45:32
And as always, you are one of the most fun people to interview. You're so great at connecting the dots. I know people have enjoyed this. So go out. If you haven't checked out his latest book, he's also got four or five other New York Times best sellers. Check them all out. They are all on my shelf back here.
Dr. David Perlmutter 45:47
Oh, thank you!
Dr. Jill 45:49
Yes. Dr. Perlmutter, it has been an absolute joy. And thank you for your time. I know time is precious, and we appreciate you so much. Thanks again for your interview today!
Dr. David Perlmutter 45:57
Thank you. Glad to be here. Thanks.
Dr. Jill 45:59
* These statements have not been evaluated by the Food and Drug Administration. The product mentioned in this article are not intended to diagnose, treat, cure, or prevent any disease. The information in this article is not intended to replace any recommendations or relationship with your physician. Please review references sited at end of article for scientific support of any claims made.