Dr David Perlmutter: So it's a brain that is literally on fire. It's a brain in which various enzymatic pathways are compromised by oxidative stress. And further, it's a brain that is energetically struggling because it is an ultimately an acquired mitochondropathy. The mitochondria within each neuron, and each neuron can have a thousand or more mitochondria, are trying to make energy for those brain cells. They are damaged by uric acid.
Dr Rupy: Welcome to the Doctor's Kitchen podcast. The show about food, lifestyle, medicine and how to improve your health today. I'm Dr Rupy, your host. I'm a medical doctor, I study nutrition and I'm a firm believer in the power of food and lifestyle as medicine. Join me and my expert guests where we discuss the multiple determinants of what allows you to lead your best life.
Dr Rupy: So when I was at medical school, the subject of uric acid levels was typically paired with gout, high purine levels in the diet and one of the most ubiquitous drugs, allopurinol, which is used to reduce uric acid levels by inhibiting an enzyme called xanthine oxidase, preventing crystals that can lodge in our joints, causing pain, typically the big toe. But there is a lot more to do with uric acid than just gout, as you're going to hear on today's podcast. In fact, there's so much more, I'm so surprised I haven't come across this subject in the past. Dr Perlmutter is my guest today and he is a board-certified neurologist and 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. 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, Neurosurgery and the Journal of Applied Nutrition. His latest book, Drop Acid, focuses on the pivotal role of uric acid in metabolic disease and was published in February this year. Don't forget, you can also watch this podcast on YouTube. Just search for The Doctor's Kitchen on YouTube and subscribe whilst you're there. And if you're in the mood for subscriptions, then you'll absolutely love my free newsletter, Eat, Listen, Read, every single week. I send you a recipe to eat, something to listen to, something to read, something to watch and a funny joke at the end that usually involves an ingredient as a caricature.
Dr Rupy: David, thanks so much for taking the time to jump on the pod.
Dr David Perlmutter: I'm delighted to be here and to spend time with you.
Dr Rupy: Absolutely. I'm really looking forward to this. You won't remember this, but when I was working in A&E in Australia back in 2014, I flew all the way from Sydney to Florida to watch you at a conference. I said hi to both you and your wife actually at the time, but you won't remember, but I shook your hand and I remember going to that conference actually, and you were one of the star speakers as you are everywhere. And you really did change my opinion on on many things.
Dr David Perlmutter: Wow. Yeah. Well, that's hopefully a good thing.
Dr Rupy: A very good thing, a really good thing. And, yeah, I just, you were a real sort of change point in the way I thought about medicine and how I kind of moved from conventional medicine to include nutritional medicine and all the other things that you talk about.
Dr David Perlmutter: And it brings up a really good point of the notion of alternative medicine means one or the alternative, the other, as opposed to integrating ideas from the best of.
Dr Rupy: Yeah, yeah, exactly. And I think, you know, conferences like the ones that we attend now, there's a lot more inclusive. And I think a lot of clinicians who perhaps are a bit more sceptical are coming around to the idea because people like yourself who are bonafide in their respective specialties are really pushing the boundaries.
Dr David Perlmutter: Right. And I think some of it also is consumer driven. I think that physicians are feeling the pressure to delineate themselves in the marketplace with some degree of uniqueness. And I think the public is demanding that.
Dr Rupy: Yeah, absolutely. Well, I was wondering where to start this conversation, but I watched.
Dr David Perlmutter: I thought we already started.
Dr Rupy: No, no, no, we are started, we're started. But we, I managed to catch a little bit of your talk earlier today, where you talked about 15 million years ago, about how we've evolved and what kind of elements in our biology we have and have sort of adapted and and why that's so essential for survival. I wonder if you can take us back 15 million years ago and talk to us about our evolutionary journey to where we are at the moment.
Dr David Perlmutter: Sure. In a couple of minutes.
Dr Rupy: In a couple of minutes.
Dr David Perlmutter: Yeah, I can't take 15 million years. Around 15 million years ago, we were in what's called the middle Miocene period. And it was a time when over about a million years, the earth cooled. And as such, food for our primate ancestors became less and less available. So it was a selection pressure genetically to determine who would survive and who would not. And a group of primates had a little bit of an advantage whereby they were able to be more thrifty with the foods that they consumed, make more fat, and therefore had basically a superpower that cultivated their survival because they could get through times of food scarcity by virtue of the fact that they laid down a little bit more fat, not that they became obese, but they would have an advantage over the next primate because he or she did not have that ability. And now it turns out that we understand what that change was. We have the ability to retroactively look at genetics of our ancestors by looking at current current day primates. And what the change was was a change in the gene suite that codes for an enzyme called uricase that enzyme breaks down uric acid. And as such, a reduction of that gene functionality led to less uricase, less breakdown of uric acid. So over a million years, their uric acid levels climbed. Now, for people who are thinking about uric acid and gout, all well and good, but it's the uric acid in the context of giving them that advantage, that extra fat, increasing their blood sugar, increasing their blood pressure that while not dramatic was enough to keep them alive and become our ancestors such that we as humans also have a uricase deficiency and have higher uric acid levels. As such, our bodies are very thrifty and want to store away every precious calorie that we consume for the upcoming winter that obviously never never evolves.
Dr Rupy: Yeah, yeah. So you mentioned a couple of things there, increasing in in body fat, increases in blood pressure, increases in blood sugar. Most people listening to this podcast will think of those things as a bad thing.
Dr David Perlmutter: Right.
Dr Rupy: But as you've quite eloquently pointed out.
Dr David Perlmutter: It's absolutely contextual.
Dr Rupy: Yeah, exactly.
Dr David Perlmutter: Right. In the context of our ancestors, it would be a home run to be insulin resistant, to have higher blood sugar, to make and store fat and have higher blood pressure. Those would be advantages as it relates to your ability to survive. Nowadays, of course, we do everything we possibly can not to have those characteristics in our physiology. And therefore, now that we understand this relationship to uric acid, we understand how powerful a tool that becomes for us in helping reduce those very metabolic issues that we need to gain control over.
Dr Rupy: Yeah. So, so let's paint that environmental picture a little bit clearer for the listeners here. So back thousands of years ago, when we have these deficiencies that enable us to have those protective mechanisms, what kind of environment are we are we living in? What kind of hostilities are we dealing with that those actually become an adaptive, an adaptive role?
Dr David Perlmutter: Well, the the real trigger for the whole process was uric acid elevation as a downstream metabolite of fructose consumption, consuming those wild berries that our ancestors would come upon, that primates consume in preparation for hibernation, or I mean, for in preparation for winter, that bears consume in preparation for hibernation. So that signalling pathway to make us fatter was adaptive and led to our survival. Now we have our foot on that of the accelerator of that pathway 365 days a year, preparing by storing and making fat for a time of scarcity that we will not experience. So that fat lipogenesis process is totally in overdrive. That process by which our bodies think it needs to make more blood sugar is in overdrive. And we see the expansive rise of obesity, overweight and diabetes globally. Now we have a real good understanding as to why it's happening.
Dr Rupy: Yeah. So it seems to me like we're utilizing ancient hardware, our bodies essentially, and we're putting it into a new context right now where we have availability of nutrients all the time. We have a dense calorie diet across all different countries. We have an abundance of of sugar whenever we want. And obviously we're hardwired to want that sugar as well. So how do we adapt our our ancient hardware for the for the modern environment?
Dr David Perlmutter: Yeah, it's a great question. In fact, it's the central theme of of Drop Acid, that we are being served to the detriment by this mismatch between our evolution and therefore our genome and our current physiology and the current environment in which we live. They're not lining up and it explains the manifestations that I just delineated of the metabolic issues that are so pervasive globally today. So how do we do that? Well, what we do is we bring the adult back in the room. Many of us, people around the world are functioning more from a more primitive brain centre, the amygdala, and making decisions without any concern for consequence. What might this decision impart on me health-wise tomorrow or next year? How might this decision not just affect me, but you or other people? We need to bring the prefrontal cortex back into the game and say, take a step back, that maybe you really want the cupcake or doughnut right now. We all do. There's nobody that goes by the doughnut factory and says, I really don't want that. We all do. But the adult in the room says, if you do that, then you're going to increase your risk for serious illness that may not be curable. And when we are able to embrace that, to take that deep breath and maybe count to 10, whatever it may be, to pull the impulsivity away from the decision making, it gives us the ability to really act with our superpower, our, you know, our brain with such a large prefrontal cortex that allows us to integrate so many inputs of our cognitive function into the ultimate outcome.
Dr Rupy: Yeah, yeah. It reminds me of the marshmallow test. I only came across this a couple of weeks ago. I'm sure you're well aware of it.
Dr David Perlmutter: Quite aware of it.
Dr Rupy: Yeah, yeah. So for the listener, the ability to delay gratification appears to be a cognitive task that we need to really exercise a lot more of. And particularly, it seems particularly relevant for this as well, as we're always going past doughnut factories.
Dr David Perlmutter: Right. I mean, everywhere. I mean, I'm walking down the streets of London and it's cakes here, cakes there. Yeah. You're sweets and you deserve them because you're good. Yeah, yeah. I mean, we grew up with that mentality. If you're good, you'll get, you know, you'll get the sweet dessert. We call children when they behave, you're acting sweet. Yeah, yeah. And what do you get on your birthday? You bombard your physiology with sugar. It doesn't do you any good.
Dr Rupy: Yeah, yeah. Well, let's dive into uric acid a little bit more. So most people, like you said at the start, think about uric acid in the context of of gout. We think about it in the context of, you know, the painful toe and allopurinol and colchicine, the non-steroidal anti-inflammatory that you use for that inflammation. We don't really think about it in the context of all the other drivers towards excess uric acid. And I think a lot of people listening to this will probably not make the connection. I'll have to explain it in the title of this podcast, but let's talk about uric acid as.
Dr David Perlmutter: So let's take it back to where you and I first learned about uric acid.
Dr Rupy: Yeah, yeah.
Dr David Perlmutter: We had a 15-minute lecture that said if your uric acid levels are high, you might get gout. And if you get gout, then you're going to take a drug, let's move on. And that's how even to this day, patients are treated. They come in with a gouty, painful toe, and they'll get put on their uric acid and perhaps colchicine acutely, and next patient, please, out they go out the door. Well, this is not your grandfather's uric acid. This is a uric acid that as wonderfully characterized by a study appearing in 2016 that was entitled Uric Acid in the Metabolic Syndrome from Innocent Bystander to to a Central Player. Meaning it doesn't happen just to be elevated in obesity and diabetes and hypertension and hypertriglyceridemia, it is playing a functional, central, mechanistic role in causing these problems. For you and me, that's empowering because it's a very new and powerful tool, addition to our toolbox, our armamentarium, if you will, that allows us to help people regain metabolic health.
Dr Rupy: And and so when looking at uric acid, how does it relate to all those other areas that we're not currently talking about? So you mentioned obesity, cardiovascular disease. What what's the connection there? What what's driving?
Dr David Perlmutter: Well, when we look at epidemiologic research, first of all, that shows relationships, it doesn't necessarily demonstrate causality. So it's a correlative type of pursuit. We see very strong correlations, and we've known this for quite some time with everything you just mentioned. So, again, interesting that we see elevated uric acid in correlation with hypertension, diabetes, obesity, etc. But mechanistically now, we've unravelled how it is that uric acid does its dirty work. And there are multiple mechanisms that it utilizes in an attempt to keep us heavier and higher blood sugar and higher blood pressure. Why? Because those were survival mechanisms. So they're very, very preserved, very powerful, and they're self-regenerative, meaning once they get triggered, they tend to keep going. So, how many mechanisms are there? Countless. One of the more recently identified mechanisms is the recognition that uric acid powerfully inhibits the production and functionality of nitric oxide. Now, why is that relevant? Because nitric oxide does two important things in the human body, aside from serving as a neurotransmitter. Nitric oxide allows blood vessels to relax. So without its functionality, because uric acid is elevated, blood vessels can't open up, hypertension and poor blood supply to our organs. Might explain why people with high uric acid have about a 35% increased risk of ischemic stroke, a 40% increased risk of dying from a cardiovascular event, because nitric oxide is compromised, blood vessels can't do what they need to do. The other issue with nitric oxide is it directly and significantly compromises both the production of how insulin works and in terms of insulin getting out of the blood vessel into the cell or to the cell membrane, and then the actual functionality of insulin once it binds to the cell membrane. So what I just said is that nitric oxide is needed for insulin sensitivity. Uric acid compromises nitric oxide and as such compromises insulin sensitivity and therefore contributes to insulin resistance. As a wonderful survival mechanism that you don't need, that I don't need, when we have insulin resistance, it paves the way for type two diabetes and all of the downstream issues related to that. And as a momentary digression, you know, recognize that becoming a type two diabetic may as much as quadruple your risk for an untreatable disease called Alzheimer's. So these are very real, important discussions. Every endpoint we can leverage to help people balance their blood sugar has incredibly widespread implications, not just for the brain, but for the heart and for the immune system and even as it relates to cancer risk.
Dr Rupy: Yeah. I'm glad you brought up the brain because I wanted to bring it closer to home for you as well in terms of how uric acid can impact Alzheimer's and other neurodegenerative diseases. Are there any other links in that way or is it is it mainly via insulin resistance that you have that impact on the negative impact on the brain?
Dr David Perlmutter: It's mainly via insulin resistance. We know that there are some important parts of the brain that are, in fact, though this is relatively new information, do in fact require insulin for those neurons to be able to utilize glucose as a fuel source. We know that various areas of the brain can alternatively function in terms of their energetic requirement with using ketones as substrate. And and while we talk about that and interventional trials whereby people with early Alzheimer's and even mid-stage Alzheimer's have been benefited by a ketogenic approach, by and large, if we can preserve those neurons' ability to utilize glucose, it's going to happen far earlier in the clinical course, even in the preclinical stage, in other words, when people are still cognitively intact. So that becomes a very, very big issue. But let me just expand that a little bit more if I can. We haven't had the opportunity to talk about this even at this conference. When glucose is elevated, as it is in the Alzheimer's brain, as much as fivefold in various parts of the brain, that right off the bat is a big surprise. That's kind of recent news that we're thinking, well, the brain is glucose depleted and therefore neurons are starving because they don't have glucose to utilize. No, as a matter of fact, it's not that there's not a lot of fuel around in terms of glucose, it's there, but the pervasiveness of that glucose to the cell and the utilization is where the compromise is. So this has become what is now known as the bioenergetic theory of Alzheimer's, which works in concert with other various other inputs to realize the disease that is given that name. But that said, by consideration, the law of mass action, if you will, higher levels of glucose stimulate a pathway called the polyol pathway, whereby glucose is transformed, intermediate is sorbitol, but ultimately into fructose. Now we're back to our fructose conversation. So you're not eating or you may be, but if you're not eating fructose, you think you're in the clear. If your brain glucose level is now elevated, you are going to produce within the brain higher levels of fructose and produce within the brain uric acid. And think about that. Higher levels of uric acid have has as its downstream consequence two very important players related to brain health and risk for disease, inflammation and oxidative stress. We've characterized the Alzheimer's brain as being the brain on fire, a brain in which even visualization of inflammatory activity is now possible. So it's a brain that is literally on fire. It's a brain in which various enzymatic pathways are compromised by oxidative stress. And further, it's a brain that is energetically struggling because it is an ultimately an acquired mitochondropathy. The mitochondria within each neuron, and each neuron can have a thousand or more mitochondria, are trying to make energy for those brain cells. They are damaged by uric acid. So that's a powerful relationship then between, you know, understanding that glucose in the brain is elevated, ultimately getting to oxidative stress and inflammation in the brain that is really a very powerfully damaging effect on the mitochondria. Now, when the mitochondria are dysfunctional, cannot produce energy, that triggers within the brain cell the pathway called apoptosis, the the suicide pathway. So now we've connected production of fructose in the brain to uric acid, to oxidative stress, damaging the mitochondria, to cell suicide and dropout, loss of brain cells as a consequence of this entire paradigm. And that explains a lot of stuff, a lot of things that were kind of hanging in the ether there for a lot, you know, many of us who are involved in research for an awful long time.
Dr Rupy: Yeah, yeah. And it sounds, I mean, to draw a very crude analogy between the brain swimming in glucose but not being able to utilize it on and there being mitochondropathy, it's almost like in type one diabetes where you have enough glucose in your in your blood system, in your blood bloodstream, but the inability to put that glucose in the right places and partition it, the the fuel correctly. So I I I understand that. And I think the inflammation piece brings me nicely on to the other the other bit about uric acid levels and how that can negatively impact the gut as well. I wonder if you could talk a bit about uric acid and its.
Dr David Perlmutter: Sure. So so much is talked about as it relates to inflammation. You've written about it in your books. And, you know, uric acid directly leads to inflammation. As one of the very big issues, inhibits nitric oxide, increases reactive oxygen, oxidative stress, leads to insulin resistance. Many of the downstream effects of having elevated uric acid are, you know, directly contributory ultimately to metabolic dysfunction and therefore the the whole panorama of chronic degenerative conditions well beyond the brain. But as it relates to the gut, uric acid directly changes the array and functionality of our gut bacteria. It directly enhances the leakiness of the gut and therefore contributes to increased inflammation by virtue of how that leakiness allows certain things to get out of the gut into systemic circulation and augment inflammation like LPS, lipopolysaccharide. It's also been interestingly noted that a treatment for gout, you're going to love this, that is very effective in reducing frequency of gout flare-ups is fecal microbial transplant. Putting back into the gut of an individual with gout, different different bacteria, fecal material from a a person without gout. So there are a multitude of mechanisms here and it's all being unravelled now and it's very, very exciting.
Dr Rupy: Wow. I can't imagine what that patient would have would have questioned when when being presented with presented with gout and then being offered an FMT.
Dr David Perlmutter: It all depends how you present it. I mean, you know, over the years, I've broached the topic to patients about, will you consider undergoing an FMT? And I cross the board, never had a pushback.
Dr Rupy: Really? Oh, interesting.
Dr David Perlmutter: I mean, even for a mother considering it as a way to help her autistic child and having watching as that child regained his ability to speak, a woman who was profoundly compromised by just an overexposure to antibiotics and just regained her life, not just with a fecal microbial transplant that she did at home using her neighbour's fecal material, but also by revamping her diet as well. I mean, gosh, she ended up on television in the States talking about this. And, you know, I get that it's distasteful and it's challenging, but there's a lot of research being done using FMT. Wonderful interventional trial was conducted at the University of Arizona, a collaborative study with Harvard researchers, Dr. Alessio Fasano, I think participated in that study, showing dramatic improvements in not only the gastrointestinal issues related to autism, but also the neurocognitive functionality as well. So we're just beginning to get our arms around what the potential can be.
Dr Rupy: Yeah. I remember actually you bringing up a few case studies back in 2015, I believe it was, when I saw you speak with parents who had autistic children and they'd had the FMT and they had some pretty drastic results. Small numbers, but still impressive enough, you know, to to warrant further investigation. Looking at.
Dr David Perlmutter: Let me just finish that thought. Not that this is necessarily the end all home run, but it's another piece of the puzzle we need to think about it, not only in terms of that therapy, that intervention in particular, but the implications about what it means that these kids have a messed up array of bacteria. And how did they get there in the first place? So, one thing we know is that the risk of of autism is dramatically increased in children born by C-section where they don't have this anointment of going through the vaginal birth canal and being exposed to vaginal bacteria. So, you know, what does that mean we should consider? We should consider, you know, having a more expensive, expansive conversation with mother and and husband about your mode of delivery more than just, well, how long will I be in the hospital and what will my scar look like if I elect to have a C-section? Sure, C-section is a life-saving technique. We get that. But it is, you know, sometimes, I dare to say, an issue of convenience.
Dr Rupy: Yeah, yeah. And I think it's those conversations that we're not having as much in traditionally practicing doctors and clinicians, you know, and after chatting to a lot of people here and over the last couple of years, it feels like giving everyone a level playing field, optimizing the gut microbiota, optimizing someone's diet, optimizing someone's psychological environment as well, can essentially create the the the sort of level playing field where health can flourish as a sort of salutogenic approach, if you like.
Dr David Perlmutter: True. But by and large, the provision of health care globally doesn't do what you just said, doesn't isn't designed to allow health to flourish. It's designed to combat disease. So, um, you know, it's a far more feminine approach. You you've been inside the lecture hall, you know, uh, that most of the people here are women. And it's because, you know, my sense is that their approach to life is based on femininity. It's more about nurturing as opposed to combating this or that, in this case, illness.
Dr Rupy: Yeah, that's a really interesting observation. I'm definitely going to pay more attention to that because you're right, every conference I've been to, it's largely dominated by and a lot of people who follow my work and buy the books as well are certainly women. Looking at uric acid a little bit more broadly now with the with the kind of diets that we've talked about traditionally when trying to reduce one's uric acid level, usually in the hope that their gout gets better or we can optimize with allopurinol. It's usually a low purine diet. A lot of foods are purine in as well, but I heard you talk about actually, from what we've just talked about now with fructose being one of the main main reasons as to why you might have a high uric acid level, we're looking at the wrong culprit.
Dr David Perlmutter: That's right. And we have, we, we've been looking at that for an awful long time. And by and large, the messaging about uric acid is in the context of gout and the, you know, it's sort of like, well, is there anything else you could do beyond taking the drug? You know, in my world, is there anything else you can do before taking the drug? And and by and large, you as you correctly characterized, it is about limiting your purines. I mean, gout was considered the king of diseases and the the disease of kings. And it was thought that because they had such high purines in their diets, that the various meats and animal products they would consume, that led the way to gout. Reality is that gout didn't really begin except for the past couple of hundred of years in humans anyway. And it did parallel the introduction of sugar into our diets, which began in 1600s to a significant degree. Yes, purines are involved, but much less so overall. It's the sugar and specifically it's the fructose. And mind you, a table sugar, sucrose is 50% fructose. So that's a powerful exposure to fructose as well. But it's challenging that the fructose messaging doesn't make its way to the very popular mainstream clinic websites who say, yes, you've got to limit your purines. Matter of fact, you don't to some degree. There are a lot of foods that have fairly high levels of purines, like cruciferous vegetables, I might add. And we don't want to limit those. If you look at the NHANES food frequency questionnaire studies involving tens of thousands of people, they demonstrated that people with the highest consumption of high purine cruciferous vegetables, kale, cauliflower, broccoli, etc., have the lowest uric acid. Same thing with fruit. So are there high levels of purines in organ meats and in small fish? There are, but most people, I think, are best served by targeting their fructose. That's that's the the best bang for the buck.
Dr Rupy: The culprits, as I'm sure everyone listening to this will will recognize, sugar-sweetened beverages, processed foods, doughnuts.
Dr David Perlmutter: Orange juice, apple juice. Yes. I mean, people seem to fail to realize, and you know, we're here visiting and staying at a hotel and you have breakfast and the first thing they want to do is pour that, you know, 12-ounce glass of orange juice. That's not natural. I don't care who made it. It's not part, it didn't come from nature. The oranges were harvested, squeezed, put in a carton on and on. And we would not normally as hunter-gatherers gather up cartons of orange juice and then drink that huge exposure of, you know, 36 grams of sugar in a 12-ounce glass of orange juice or apple juice, overwhelms our small intestine's ability to deal with the fructose load, which is about 5 grams at a time. So that overload of fructose is then processed in the liver and then sets the stage for increasing our blood sugar, increasing our lipid fat production, activating the production of uric acid and all of those downstream issues that we've talked about.
Dr Rupy: Yeah, absolutely. I always ask people to just imagine how many oranges or how many apples are utilized to create that small glass of juice that you're about to consume.
Dr David Perlmutter: That's right. In the absence then of fibre and the bioflavonoids to some degree, if it's been treated, and certainly, you know, vitamin C. So it's not a natural experience to bombard your body with that much sugar at a time. It overwhelms us basically, and it sends a powerful signal to your body, prepare for winter.
Dr Rupy: Yes, exactly, which is leading to the obesogenic effects and everything. We talked a bit about the foods to sort of take out of the diet. What are the the things that we want to include into the diet that can be uric acid lowering?
Dr David Perlmutter: Well, foods like red onion, for example, asparagus, artichoke, various vegetables are high in various types of what are called bioflavonoids that actually help us reduce our production of uric acid. They work by inhibiting the same enzyme that the drug does, allopurinol, the enzyme is called xanthine oxidase. So drugs that are high in these bioflavonoids, like luteolin and quercetin, tart cherries, for example, are long recognized as being associated with lowered uric acid. So we can eat those foods and we can take those active ingredients, if you will, quercetin, luteolin, etc., as supplements and really go a long way to help us lower our uric acid.
Dr Rupy: Yeah. Talking a bit in the context of our body having ancient hardware and putting ourselves in a modern environment, we would also have been exposed to different changes in weather, changes in food availability, things that we don't have to deal with right now. I mean, we're we're sat here in an air-conditioned room whilst it's like 33 degrees outside, 33 degrees centigrade outside. We have an abundance of foods flown in from all around the world. If I want a cherry today, I can also have one a cherry in December. You know, we're exposed to sort of this flat of of comfort. Everything is is very comfort orientated. So how do we actually push our body to to experience some of those hormetic effects?
Dr David Perlmutter: Great question. There's a book that I just finished reading called The Crisis of Comfort by Michael Easter. And he he writes about the fact that we need and and the book goes through everything you've talked about through, but interspersed with his experience of being, I think 30 days in in Alaska, having to hunt and animals and you know, really being challenged. But that said, there is, you know, significant health upside to being uncomfortable and to experience these challenges to the extent that it is stressful to us from a thermal perspective, hot or cold, from a caloric restrictive perspective, being starved, if you will, or calorie restricted, from overdoing it with respect to exercise from time to time. And you use the term hormetic effect, of course, so that we it's it's a lot like lifting weights. When you lift weights, you tear down a little bit of muscle fibre, then you build it back to where it was and then a little bit more. So you end up net positive. That's how you build muscle. And and so it is with hormesis that we experience a stress, we deal with the stress, we get pushed back a little bit, one step backwards and end up taking two steps forward and we become better for the event.
Dr Rupy: Yeah, yeah. This adaptive mechanism is fascinating. And in the context of how we should be challenged at various points, we can definitely do things like exercise, we can eat bioflavonoid rich foods that have that hormetic effect at a cellular level. What about the patterns of eating that we're we're accustomed to across a 12-month period? So is there a rationale for having a different macronutrient composition in the winter versus spring versus summer? Should we introduce like a ketogenic diet at certain times and then a more carbohydrate rich diet at other times?
Dr David Perlmutter: I would say by and large, no. That may be a surprising answer for you. And the reason being is that we don't have to adapt anymore for the change of seasons because our our environment is totally controlled. We have clothing that keeps us warm. We have our homes that are heated to 72 degrees Fahrenheit, 365. So that the notion of trying to eat foods in season, why while that is ideal, when this when we are going to be confronted by seasonality makes sense. I think it's less relevant today.
Dr Rupy: Yeah, yeah. And and since writing, you know, your your first books that are widely popular, influence a lot of people, are there things that you've changed your opinion on or you've you've sort of progressed on or built on top of?
Dr David Perlmutter: Indeed. And I I will tell you that that doesn't go unchallenged. People say, oh, Dr. Perlmutter, when you wrote Life Guide, a book I wrote many, many years ago, you told us we should be on a low-fat diet. That was what, 25 years ago? And, you know, that was a mentality at the time based on currently available science. So messaging should change over time. And I think that it's important for people who who follow, dare I say, influencers, to recognize that you want them to be adaptive and flexible and be able to admit that things are different now. I'd say mostly a biggest a bigger change in our diet has been more plant-based for a variety of reasons, though we're not fully plant-based, that's for sure. I think over the years, the science on the value of exercise has become much more well-defined so that has become much more, well, plus I'm older and so it becomes much more important anyway. So that's become much a much more central part of the messaging. The value of sleep has become much more central as well. But I would simply say that things are going to change. I mean, the whole uric acid paradigm is relatively new, despite the fact that the first book talking about uric acid outside of the constraints of gout and kidney stones was written in 1898.
Dr Rupy: Oh, wow.
Dr David Perlmutter: Yeah.
Dr Rupy: Wow.
Dr David Perlmutter: That's right.
Dr Rupy: Yeah. And so with that in mind, and I think it's, it gives you a lot more respect, I think, the fact that you're willing to change your opinion on things from the low-fat era to the era now. What do you make of the higher fat, the ketogenic sort of modes of eating? Is that something that you encourage or does it really depend on the context of the patient? Do you see it as a therapeutic tool or a preventative?
Dr David Perlmutter: There is no question that a ketogenic diet can be therapeutic in my world as it relates to both Alzheimer's and Parkinson's. So that that research is very compelling. My sense is that as far as the population at large is concerned, to get into from time to time a state of ketosis, I think is reasonable to keep that mechanism active and available as having a flexible physiology. I don't think that remaining in ketosis full on all the time is necessarily the goal. And I think most of the advocates of ketogenic diet would probably agree with that, that cycling back and forth is the way to remain most adaptive and flexible.
Dr Rupy: Yeah, yeah. I I think, um, certainly periods of going into and out of can be useful, particularly given the the clinical context. And also just generally, um, changing one's diet from time to time. We had Walter Longo on the podcast a year and a bit ago and and more recently as well. And I think that concept of stressing your body from time to time is is going to become necessary, particularly as we're quite comfortable.
Dr David Perlmutter: That's right. I I spoke to him yesterday, oddly enough, about these topics. And, um, I think it's a job in process, a work in process. I think we don't yet know, but I think one dictum that remains central and that is, you know, the work of Dr. Lauren Cordain in the 60s that we really need to consider emulating as best we can the environment of our ancestors in and trying as best we can to re-establish this relationship, cultivated relationship between our environment and our genome, our environment and our evolution, the gift that we've received. And we we can't. I mean, we can't go out and be hunter-gatherers anymore. But that said, we should look upon our current environment in terms of how it deviates most aggressively from that of our ancestors and really address those those factors. Whether it means, you know, more stress by getting out of doors more and being in a less controlled environment, certainly limiting our exposure to fructose and other things that have entered into the modern diet, these are not hard to accomplish.
Dr Rupy: Yeah. Do you fast at all?
Dr David Perlmutter: Oh, we do. We do fast. Yeah. In fact, we did last year our social media fast. And we had, I think we had 10,000 people fasting together.
Dr Rupy: Fab.
Dr David Perlmutter: Oh, it was wonderful. We had a, I forget what you call it. It's there's a special name for it when everybody gets together and does something online. So the answer is yes.
Dr Rupy: Yeah, brilliant. And was that a social media fast or was that like a like an FMT thing?
Dr David Perlmutter: Oh, I get what you're going. No, it was a food fast. It was not eating for. Okay, right. Yeah, but it was done on social media. But fasting from social media is makes sense to me as well.
Dr Rupy: Absolutely. Yeah. I was going to ask actually as we bring this conversation to a close, I mean, you've been a pioneer in a lot of communities. I mean, over here, you're very well known as well. Um, you must have got a lot of backlash over the last couple of decades of publishing books and everything, criticism.
Dr David Perlmutter: You bet.
Dr Rupy: Yeah, yeah. How do you, how do you deal with that?
Dr David Perlmutter: I I I'm supported by that. When I stop getting pushback, I'm then status quo. And Ronald Reagan, one of our presidents, once said that status quo is a Latin term for the mess we're in. So I think it's it's good to challenge whatever we see around us, right or wrong. You know, I've been wrong about things that we have, you know, been in favour of for at times. And, you know, Thomas Edison said that he learned more from his 99 failures than he did from the one success. So, you know, people say, well, what you're doing is outside the box. That's not the goal. The goal is to make the box bigger. To make, to really augment inclusivity with ideas that seem fringe because ultimately they'll people say, oh, it becomes self-evident that we knew it all the time. Well, not so much, but the whole idea with uric acid, it's we're right at the beginning of that, uh, whole incorporation of uric acid into our understanding of what leads to metabolic dysfunction. And I I suspect that in two years when we get together on a podcast again, or whenever that may be, we will be appreciative of a much more expansive understanding of the role of uric acid in metabolism.
Dr Rupy: Yeah.
Dr David Perlmutter: Maybe not, who knows?
Dr Rupy: Who knows? Yeah. Well, I love that growth mindset. That's brilliant. Uh, just as we as we bring this to a close now, any mental health tips? Like how do you look after your mental well-being on a day-to-day, particularly when you're travelling and and moving around so much?
Dr David Perlmutter: Well, I have a wonderful marriage, first of all, and that, uh, more than anything, I think has kept me, uh, in a great place. Uh, you know, beyond that, I think exercise is important, dedicating to sleep, uh, with travel especially, limiting to almost no alcohol during the travel part, I think is really very important. Um, and what I I really try to do more so lately is to do one thing at a time. Have a conversation with you right now, uh, have a meal at a given time, not be checking text messages. It's so tempting. I want to look something up, you know, ask Siri something because I really want to know who starred in that movie because it's part of our conversation, but not to do it, to be dedicated to the moment. I think is really important.
Dr Rupy: Yeah. Well, that's wonderful advice. I'm getting married this year, so hopefully, yeah, I've taken your advice already. I'm sure I have. She doesn't listen to the podcast anyway, so it's fine.
Dr David Perlmutter: Well, I would say also now that I know you're good for good for her as well, too.
Dr Rupy: Oh, brilliant.
Dr David Perlmutter: Hearing you.
Dr Rupy: Thank you, man. I appreciate that. Well, thank you so much for coming on. It was an absolute pleasure. Absolute pleasure. Really do appreciate it.
Dr Rupy: Thank you so much for listening to this week's podcast. You can check out the Doctor's Kitchen app that you can download for free from the App Store. We're building the Android as we speak. Plus, you can subscribe to the Eat, Listen, Read newsletter every single week. I send you something to eat, something to listen to, something to read, something to watch with a funny joke at the end every single time. I will see you here next time.
