Brain on Fire: How Dietary Induced Neuroinflammation Causes Mental Illness, Aggression, Violence and Dementia
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- Coming up on this episode of The Doctors' Pharmacy. - So what happens in the gut impacts the brain and vice versa. There's a couple of pathways that have been isolated. - Top down, bottom up. - Right, I guess bottom up being more specific in this case to the gut and the brain, but sure, both ways. And again, I think we will learn in the future that maybe this part is not in as much control as we thought. - Welcome to The Doctors' Pharmacy. I'm Dr. Mark Hyman. That's pharmacy with F, a place for conversations that matter.

And the truth is this conversation relates to everyone because we are having an epidemic of brains on fire.

something called neuroinflammation, which is affecting so many things that we're going to talk about in a minute. And our guest today is a incredible physician, Dr. Austin Perlmutter, who is deep into this topic of neuroinflammation. He's a board-certified internal medicine physician, a New York Times bestselling author, and he talks a lot about neuroinflammation in his book called Brainwash. He's also a published researcher and an international educator. His mission is to help people improve their health

by targeting the biological basis of stuckness in our brains and bodies. Who wouldn't want to be free of stuckness? His writing, presentations, podcasts, and online educational programs explore how environmental factors influence our cognitive and mental state, and they've reached millions of people. He's been featured on PBS, Rolling Stone, Newsweek, NPR, and a wide range of other outlets. He's the co-producer of Alzheimer's, the Science of Prevention series, and the host of the Better Brain Blueprint series.

He currently serves as the managing director of Big Bolt Health, a food as medicine company focused on helping people rejuvenate health through better immune function, where he is running a first of his kind study exploring the effects of plant nutrients on human aging through epigenetics.

Now, why this conversation is so important is that we are seeing an explosion of brain inflammation disorders. Everything from mental health crisis with depression, anxiety, bipolar, even psychosis, schizophrenia, all connected to brain inflammation, not to mention ADHD, autism, and even memory issues like Alzheimer's, all connected to brain inflammation. And what's more

What we talk about in this podcast is how that brain inflammation is affecting us as a society, leading to increased divisiveness, strife, oppositional behavior, aggression, violence, all of which may be linked in small or large part to neuroinflammation. So we talk about how do we identify neuroinflammation, what causes it, how to resolve it, and what to do about it in this fascinating conversation with Dr. Austin Perlmutter. Let's dive right in.

All right, Austin, welcome to the Dr. Sronstein Podcast. Mark, excited to be here. Excited for the conversation. So just as background, you know, your dad and I go back a long time. A little while. And we've been friends for a long time. David Perlmutter wrote Brain Brain. Together you wrote Brain Wash with him, which is really going to be a lot of the topic we're going to talk about today. We had you on the podcast a number of years ago when that book came out with your dad. And your dad really was one of the pioneers in helping us think about

brain inflammation. And you are now heavily focused on this whole topic of why our brains are inflamed, which leads to so many downstream problems and pretty much everything that goes wrong with the brain from autism to Alzheimer's, from anxiety to depression, from bipolar disease to schizophrenia to Parkinson's. I mean, you name it, anything that's going on in the brain that the brain's not working,

It doesn't have a way of like saying, ouch, if your joints inflamed, it's red and sore and it hurts when your brain's inflamed. It comes out as all these other manifestations and diseases. And so you've been deep into the topic of this. And I've been very impressed with your thinking about it. I just really came from a lecture that you gave at the Integrative Health Symposium here on neuroinflammation. I learned a lot, actually. And it really seems to me that we are

in an era of massive inflammation. Your dad used to show this slide with the brain on fire. And I think our brains are on fire, our emotions are on fire, our society's on fire, polarized, disconnected. There's more aggression, more violence, more depression. We have a massive mental health crisis, opioid deaths, disease of despair, and

There really doesn't seem to be a very coherent approach to it, right? Other than suing the Sackler family for OxyContin, which isn't really a solution. There really doesn't seem to be a lot of coherent thinking about it. And I've read even some crazy studies where they were like, "We're going to use these drugs called TNF alpha blockers to treat depression." Because now we know the brain that's depressed is an inflamed brain.

And I'm like, wait a minute, you're going to take a $50,000 drug that increases risk of cancer and overwhelming infection and death to treat depression. How about figuring out the cause of the inflammation? So let's talk about neuroinflammation as a concept. What is it? What's causing it? And why are we seeing such an epidemic of neuroinflammation?

And by the way, it's not really something I ever learned about in medical school. So you got new graduate medical school a lot more recently than I did, but I bet you didn't learn a lot about it either. So kind of walk us through this whole kind of conceptual framework of neuroinflammation and why we should care about it and what it's causing and why it's happening at such the rate it's happening.

Well, I think, Mark, let's start with the basics here. So it's the understanding that as we look at how people are doing today across the world, we have to have a realistic moment of pause to ask whether people are doing well. Are people getting better across the planet? Something we've talked about. Is this a multiple choice question? Because the answer is hell no. Or none of the above, depending on how you look at it.

So I think you can look at all these different disease states, but if you look at kind of underlying the lowest common denominator, for many of these cases it is chronic inflammation. We understand this in the body. So seven out of ten of the top causes of disease and death on the planet today are these chronic diseases, of which many of these are driven by chronic inflammation. And we've come to terms with this as it relates to what's happening in our body. There has been this fundamental disconnect though

with this expectation that we don't need to look at the brain in the same way. And you alluded to this with this strange sense of if inflammation is happening in the joint, we can point to it. We can say that there's a problem in this joint. And it is customary if a person has pain in their joint for them to go to the store and buy an anti-inflammatory medication. Like Advil or Aleve. Exactly, an NSAID.

This is pretty prototypical. This is the way that we look at inflammation. We have kind of this loop that we follow. But what does it look like when inflammation occurs in the brain? And you've referenced some of these diseases, but what we know is, so of the 300 plus million people around the world right now experiencing depression, a sizable proportion of them have elevations in serum inflammatory markers. And so it's believed that... - What you're talking about there, Austin, is like the cytokines. We've heard about in COVID,

The cytokines are the messenger molecules of the immune system. And what you're saying is that the 300 million people out there with depression have high levels of these in their body. Right. So statistically speaking, that people who have depression have a higher likelihood of having evidence of elevated inflammation. You can measure it in a number of different ways.

This is so important though, not just in depression, but for conditions like Alzheimer's because by and large, as we look at these brain diseases, the standard of care sucks. It's miserable. So if you go through- - Is that your official medical diagnosis? - It's miserable. This is the code. The point being though, if you were to look at, let's say depression, for example. So again, 300 plus million people around the world who are experiencing depression right now. If you look at the kind of hit rate for our conventional antidepressants,

Roughly 50% of people will get a substantial improvement. Roughly 33% of people will get a actual remission. And somewhere in the neighborhood of 20% of the American population is going to be diagnosed with major depression. So thinking about what that means in practice, our conventional therapeutics are not doing a good enough job.

Similarly, when we look at Alzheimer's disease, so we look at conventional drugs for Alzheimer's, they just don't really work to actually mitigate the disease process in a meaningful way.

Pausing there for a second, we say, "Is that sufficient?" The answer is no. We need to keep looking. And then we start to ask what systems within the body can help us to explain what is going wrong. And recently, as two years ago, a paper came out looking at serotonin and the serotonin hypothesis of depression, basically debunking the idea that serotonin was the principal driver of why people experience depression. - You mean low serotonin? - Well, so low serotonin, but also changes in the receptors, changes in how those pathways are activated.

The majority of our antidepressants work in theory on serotonin pathways, but it hasn't necessarily been proven. So it leads us to this conversation about is there another system at play? And inflammation has really risen to the top as it relates to potential ways to explain what is going wrong. What's really important and what I think we're going to get into here, it's not just talking about diseases.

And we've got to get away from thinking that health starts when you get a diagnosis, something you've talked about extensively. So for everyone who's out there listening and maybe doesn't have a diagnosed mental health condition, doesn't have a diagnosis of dementia, this stuff still really matters to you because as we can talk about, inflammation is driving every aspect of who we are, how we feel, how we interact with the world.

And to that end it means that modulating, changing our inflammatory balance in the body and in the brain is a way for us to change how we show up in the world. So not just at the extreme ends when things have gone so catastrophically wrong that we say you have a diagnosis, you need a therapeutic. But even in the day to day if you want to think better, be better in your relationships, help the planet, that is an inflammatory outcome. - Yeah, I mean even if you don't have a diagnosable disease,

Any level of inflammation that's a little bit out of control in the body will contribute to dysfunction, which can be symptomatic as brain fog or fatigue or just not sharp or a little depressed, a little mood stuff. But you're not meeting the criteria for a disease. I call it FLC syndrome.

That's when you feel like crap. Another official diagnostic code. Absolutely. And a lot of people have it out there. You know what I'm talking about. And I think it's important to start to realize we need a different thinking approach

framework for how to assess this issue because our current assessment of psychiatric disease, of neurodegenerative diseases, of neurologic diseases is sort of archaic. It's very descriptive. We're good at describing things and labeling things, but there's kind of a joke in neurology which is diagnose and adios or treat them, mistreat them. Basically, get them out of the door because there's not much you can do for them.

And the truth is there's a lot that can be done. And your dad has really pioneered a lot of the ways you're doing it. You're leading the way now. And I think that we need to sort of think about neuroinflammation as this common framework for understanding a lot of what's wrong with our brains and all the things that go wrong with our brains, from all the mood disorders, attention disorders, autism disorders, neurodegenerative disorders, all these things that we don't really have great treatments for in traditional medicine are actually very important

amenable to treatments that address the root causes. - And I'd say prevention, and I think that's key to this conversation. So I don't know what it was like back when you were learning these strategies, but for the most part, you screen for depression in the clinic, and if a person meets criteria, then they get into the algorithm. Person's feeling a little bit low, you maybe make a note in the chart, but you're not necessarily following up on that. We'd say that's part of the spectrum of normal human experience.

We do a similar thing when it comes to MCI or pre-MCI, meaning mild cognitive impairment. What we're talking about- - Pre-dementia, what you're talking about. - Exactly, exactly. So if a person comes into the clinic, they say, "I'm not really thinking clearly." You might start a workup, you might check B12 and some other markers, but in a traditional sense, you're not necessarily doing much until they've received a diagnosis. So what about somebody in their 30s who's coming in saying, "You know, I just don't feel like I'm as sharp as I used to be. What can I do?"

conventional medicine would say, well, exercise, get some good sleep, and we'll do some evaluations in the future unless things get really bad. And to that end, I'd say again, prevention is the key. It's my belief, and I don't know if you share this, that mental health is kind of the absolute final outcome that we need to care about. It's what makes life worth living. Everything else is a surrogate marker for mental health. - Yeah, it's true. - And if that is the belief, then we should be asking-- - It determines the quality of our life, the quality of our relationships.

determines our behaviors because if we're not happy we're gonna do something might be self-harming like eat junk food or not exercise. That's it. Drink too much or... Yeah, I mean if you push somebody hard enough and ask them why do you care about that? So maybe they say I'm really I care about making a ton of money. Why? What does it mean to you? Eventually you get to it makes me feel good and that's kind of at the end of the day the thing that matters most. So if we agree and hopefully we do that mental health matters more than anything else then if we work backwards we say what are we actually doing to optimize for mental health?

And for the most part, we do very little until things get bad enough that it necessitates a diagnosis, pharmaceuticals. And that's just a problem because we take so much time now to think about preventive cardiology, right? You should be jogging each day to decrease your risk of heart attack.

What are we doing each day to prevent depression, to prevent anxiety, to prevent Alzheimer's disease? I would argue that is even more important. So yes, heart disease kills more people than does dementia and Alzheimer's directly. But if our goal is quality of life and mental health, then that actually should come first. I think that's just such a critical point you just made because, you know, we think about certain things like, oh, I can prevent diabetes if I eat better. I can prevent heart disease if I exercise and eat better and reduce stress.

And there's sort of an understanding within traditional medicine, even though it's not applied, right? Just take your statin, right? It's like, take your Ozempic. But there's not even a framework for understanding how to improve brain health or prevent brain diseases or prevent depression. And the truth is there's so much we know about this. It's in the evidence-based literature. It hasn't been translated into clinical practice. And that's really one of the fundamental problems in medicine. It's just such a lag time. And even within...

traditional approaches, just a lag time. And forget about things like systems biology and medicine, network medicine. I mean, the gut microbiome plays a huge role in mental health, but how many psychiatrists are checking a poop test? - Not a lot. - Not too many. - I think to go into that for a second here, I mean, think about where we should be heading as it relates to upstream thinking for depression.

Our population is one, and I'll try to say this as carefully as I can, where, at least in the United States, it behooves most interest for us not to have solved for mental health. And why is that? It's because when a person is...

When a person is feeling good about what's going on immediately around them, when their cup is full, they're not as likely to buy all the unnecessary stuff, to fall victim to all of these unnecessary ploys for their money and for their time. So this is not to say necessarily that we've created an evil society. It's simply the fact that our incentive structure has very little to do with better mental health.

The opposite. Exactly. It is better for most large entities, corporations, companies, for us not to feel good. Because if we feel good, we don't need their X, Y, or Z. I don't know if you saw that, Austin, but there was a recent article in Fortune magazine

about the CEO of the company that makes Ozempic, which by the way, I don't think they sell in Denmark. It's the biggest contributor to the GDP of Denmark right now.

And the CEO kind of called it out, but he was getting phone calls from all the junk food makers concerned that they were going to be in trouble because of this drug cutting into their market share or stomach share. And I think, you know, when I don't know if you saw the Super Bowl, but this year in the first half, there were 11 commercials for junk food. The rest of the commercials were other than the Christmas.

Christian commercial, where we're basically addicted to things, gambling and alcohol and junk food. So when you think about what's being told to us and the things that are being shown to us and the pressures on us to kind of consume and buy things that are going to numb us, dumb us down, make us sick, it's kind of frightening. It's literally like, wow, this is the most watched show on television. And

The entire show was punctuated by pushing us to become more addicted and more depressed and more obese and more sick

And it was sort of striking to me. And I was like, wow. It's also just a great representation, a snapshot in time as to which companies have enough might to be able to afford those ads on TV. So their margins are big enough that they can put up a couple million dollar commercial for X, Y, or Z. And that is a direct reflection of the fact that there is that degree of consumer buy-in. You're absolutely right, though. I mean, it's always the irony of watching professional athletes and then watching them in commercials.

advocating for the things that would absolutely destroy their careers if they continued to consume. But you're right. So whether it was the beer or the food or the gambling, these are the things that we default to

And again, I think there's an important point to be made here, which is it's easy to go to the place of saying evil corporations. I think it's just this is what corporations are incentivized to do. And humans find places of minimal resistance or least resistance. It has been discovered by people over the time that we've had marketing that when you make things appeal to more primitive parts of our brain, when you take away psychological pain,

that people are more likely to buy your product. So whether that's a sugary food or a gambling app on your phone, you are in essence taking away short-term psychological pain at the expense of long-term health. And I think that is the fundamental nature of the problem. We have in essence outsourced decision-making to corporations that are not evil, but rather do not have our best interests at heart. - I mean, like when you're putting little children in functional MRI machines and showing them images of different junk food and seeing which

images light their brains up the most so they'll be likely to want it and buy it or whine and cry and scream until they get it. - Yeah. - I don't know about that. - You're gonna use the term? - That borders on evil to me. I mean, listen, those are our children. Those are the future of our country. - Absolutely. - If we're actually figuring out how to make our children addicted through sophisticated scientific investigations and experiments,

That's frightening to me. And by the way, I'm not making this up. This is in the New England Journal of Medicine. This is published data on what's actually happening with food marketing and children in this country. So I don't want to get too down that rabbit hole. What I want to come back to is the neuroinflammation because I think it's frightening how much of a problem this is, but it's also encouraging that there's a real pathway in our understanding of science about how to modulate inflammation through diet, lifestyle, nutrition,

nutraceuticals, other therapies that can actually help to fix the brain, to repair the brain, to improve the connectivity of the brain, to reduce the amplitude of the

the anxiety and depression and the aggression and the violence and the behavioral issues we're having in the societal polarization all not to mention all the neurodegenerative diseases and all that stuff you know we know how to do this it's not like you and i do this in clinical practice this is something we see in our patients and it works but most people don't have access to this so why don't we kind of back up and talk about what is neuroinflammation and and what

Why does this happen? - Right. So neuroinflammation is a little bit variable as far as how it's defined. I'm gonna use some technical terms here and then you could walk me back if we go too far. But basically what we're talking about is an activation of the immune system within the brain with certain markers that tell us this is inflammation. Inflammation is just a state of activation of the immune system.

In the brain, what we're talking about-- - No, no, inflammation's bad. You need it. You've got a cold. You want inflammation to fight the virus. You've got COVID. But if it's overactive and it's overactive for too long a time and it's triggered by the wrong things, it's a problem. - Exactly. Exercise increases inflammation, but it's not bad because it's a short burst of inflammation that over time actually suppresses inflammation. - That's right.

As a caveat here, what we're trying to talk about is either an incredibly high level, so something like what might have been seen in the cytokine storm, or a chronic low level, which is what we really see in metabolic diseases, and that's the one that's been more associated with conditions like dementia and depression. So in the brain, what we're talking about is one, a breakdown of the blood-brain barrier. That's the barrier that surrounds the majority of the brain and is supposed to help protect the brain from what is happening in the bloodstream.

The second thing to consider is that the brain has immune cells within it. And this will be news to people who think about the brain as separate from the rest of the body. - Yeah, that was a big lie we were told in medical school. The blood-brain barrier, nothing gets through. - Nothing gets through. - I'm like, well, not really.

We have leaky brains, guys. We're gonna talk about that. Think about what's in your brain right now. I guess your brain, Mark. You probably have somewhere in the neighborhood of 80 to 100 billion neurons, which is amazing. That's plenty. You're doing great. But the really interesting part of it is that you have about the same number of glial cells. These are the cells that, in essence, do so much for how you think, how you act, and how you feel, and in some ways kind of tell your neurons how to behave.

Of that number, something like 20 billion are a cell called a microglial cell. And a microglial cell is a bonafide immune cell that lives in the brain. Its role is not just to protect the brain against outside threats, but it's actually an immune cell that modulates how neurons fire, how they work. And this is really the cell type that has been very carefully researched as it relates to increasing our risk for brain health conditions, mental health, cognitive health conditions. It's like the immune system of the brain.

It is. If you're going to remember the immune cell of the brain, the answer is microglial cell. But I will say, and as I talked about earlier, it turns out all the cells in your brain participate in immunity. Neurons are immune cells in that capacity. Astrocytes, oligodendrocytes, they all kind of participate in this immune conversation.

But for the purposes of this, the one to know is the microglial cell because they seem to be the master orchestrators of your brain's immune state. And in doing so, regulate whether your brain is inflamed or is moving towards more of a state of resolution and anti-inflammatory state. And so...

How do you measure that? Like, you know, I'm a doctor. I'm like, how do I measure brain inflammation? I'm going to go take a little burr hole. Yeah. You know, brain biopsy. Measure the tissue. Don't do that. Yeah. Don't do that in the clinic. That's not a good idea. It's a great question. And you are using most of your brain right now, as am I, hopefully. You don't want to be taking out big pieces of tissue to study under the microscope. So unless a person is hospitalized, unless something's going pretty seriously wrong, we're not going into the brain to take a biopsy.

So in the absence of that, exactly, or an infection, right? You need to know whether it's infection or malignant. But in the absence of that, certainly you can look at CSF again. This is spinal fluid. Exactly. Not super convenient. So we wind up looking at other tests. There's a lot of imaging research that's been done using MRI, using PET scan to look at various kind of correlates of inflammation.

And this gets technical again, but there's a certain type of protein called TSPO that when activated, when we see more of that on imaging, is an indicator that there may be more activation of microglial cells, inflammation in the brain. - So now there's advanced imaging that looks at the brain on fire, but it's not really available for everybody. - It's not something that we should be-- - I don't have one in my clinic. - Right, we shouldn't be routinely testing that. And to that end, the important piece

is to look at the data that we have available and that can be everything from waist to hip ratio. It can be looking at a hemoglobin A1C. It can be looking at potentially things like zonulin, insulin resistance. These are surrogates for inflammation in the body and they correlate with risk for neuroimmune, neuroinflammatory diseases. Okay, so I'm going to unpack that a little bit because it was a big mouthful and I went fast, which is essentially what you're saying is

People have biomarkers of poor metabolic health. And by poor metabolic health, we mean somewhere on the spectrum from slightly imbalanced glucose and insulin regulation to prediabetes, to full-blown type 2 diabetes, which leads to increased belly fat, which is very inflammatory.

and it leads to other biomarkers in the blood, like C-reactive protein. You mentioned zonulin, which is a marker of something that gets triggered in the gut, often in relation to gluten, that can cause a leaky gut. And we'll talk about the gut brain in a little bit more detail, because I think that's a really important center for the source of inflammation in the brain. And so basically what you're saying is between kind of the gut being messed up and our

diet and its consequences for our metabolic health, that's driving a lot of the brain inflammation that's related to the ultra-processed food and starch and sugar and refined foods that we're eating that are generally inflammatory. I think to expand it a little bit, if you look at... Did I get that right? You're correct. But to expand it a little bit, your brain is a reflection of the inputs you give it, what you consume.

And if you think about what you're consuming, of course it's what you put into your mouth, what you swallow, the food that you eat. It's also what you inhale, so it's a reflection of the quality of the air you breathe. And then the piece that many people don't pay enough attention to is what you consume through your eyes and through your ears. And so I'd say in that sense, it is an ultra-processed consumption.

data from a number of sources that it is a very easy one to get into because it's something we have a choice around Some of us don't have as much choice around the other pieces, but certainly all of these things contribute to brain inflammation Yeah, I mean I was thinking like you know the the media that we now mostly consume whether it's news or social media Is basically like junk food for the brain. Yeah, it's highly effective. It's no nutrients. No new trends. That's like I

It's not up leveling yourself. Not at all. I mean, it's a sink, a cesspool of stuff that activates anger and activates your primitive limbic brain, your amygdala, your dopamine activation. You end up in this vicious cycle of addiction to that too. I mean, I noticed it myself. I'm like, I want to see what's happening in the world, but it shouldn't be called news. It should be called bad news. But there's so much good news happening in the world we never hear about. And I think

We really have to think carefully about what we ingest, both like you said, through our mouth and through our eyes and our ears and our relationships as a big factor. Because all that, whatever the input is, the end result is the same. I always think of inflammation as the final common pathway for bad stuff.

So if there's insults, it's sort of the way the body responds. And it's through activating this inflammatory process, this fire in the body, which also ends up in the brain. You're right. I think taking a moment here to consider this through kind of an evolutionary lens, if we may.

One of the experiences that many people may be familiar with is how they feel when they get sick. So if you got a cold, if you got the flu, if you came down with some illness, how your thinking is and how you interact with the world. This has been deemed sickness behavior. This is the terminology for it because humans, by and large, when they get sick, act and feel in certain ways.

What's really interesting about this is they feel depressed. They feel socially withdrawn. And so it's been hypothesized that this makes sense, again, evolutionarily because you want to be somewhere safe. So you want to kind of go back somewhere that you can recover on your own and you don't want to infect other people with whatever sickness you're experiencing.

So that makes sense in the context of an illness. But think now about the fact that really what it is, is inflammation telling your brain how to behave and how to withdraw from other people and how to have more kind of walls up against maybe hearing what other people are talking about.

now appreciate that that same inflammatory pathway may be chronically activated by our interactions with the modern world, then you can start to understand perhaps some of the behavioral changes we're seeing at scale across the planet with polarization, with people in essence having more trouble connecting with others. This is really, I think, an impactful way to look at the real power of the immune system is changing human behavior at scale.

I mean, this is a really important topic, Austin, because it's not being discussed much. We're understanding that maybe bad food causes depression, maybe a metabolic syndrome and insulin resistance lead to Alzheimer's disease, and that there's this sort of inflammatory process that happens as it relates to lifestyle, but not really in terms of our way of seeing the world, feeling the world, connecting it. And there's a really important kind of

thing for people to understand and maybe you can unpack a little bit is this relationship between what I call the adult in the room and the lizard brain. And the lizard brain is like, it basically wants to do what it wants to do when it wants to do it. It's focused on survival. So it's feeding, we used to call it the four F's in medical school, feeding, fighting,

or fleeing or reproduction. And that and that and that is also maybe fawning is another one of those. But there's these behaviors that are just ancient

behaviors that are built into our brain that if we listen to all those things, if we act on all those thoughts, and we all have those crazy thoughts, whether it's I want to eat that entire pint of ice cream or I want to go and make out with that person I saw on the subway even though I don't know them. You have these crazy thoughts, but you don't do it because you have an adult in the room that says, "No, that's probably not such a good idea, Mark. You probably don't want to do that."

And so what's happening, and this is what fascinates me with the science, is increasing amount of scientific literature that points to inflammation as being an interrupter of the communication between the adult in the room who makes coherent decisions that protect themselves, their community and society, and the kind of reptile dinosaur in the room that wants to attack and eat everything.

So, can you explain the science behind this? And you did a lot of work on this in your book, Brainwash. Right. And I think it's becoming even more relevant as we're seeing our society break down. And as we're seeing this, you know, globally we're seeing polarization. Globally we're seeing increased hatred, increased violence, increased polarization. Right.

And it's really concerning to me, and I think there's a solution for it. But can you sort of explain the science behind this disconnection for people? The idea here is, as you've alluded to, we have ways of looking at parts of our brain. Everything, of course, is networked. But certain aspects of our brain, when they communicate in a positive way,

seem to help regulate our decision-making process. So the area of the brain that we really focus on is the prefrontal cortex as being that adult. When the prefrontal cortex is active, when it's kind of able to do its job, it is able to calm down and speak to the more

perhaps primitive parts of our brain that are very helpful, very necessary, but shouldn't always be the ones making decisions. So if you think about it, the primitive parts of the brain are the ones that hear a bump in the night and think there's a monster under the bed. That doesn't probably make sense to most adults, but it might pop up. Maybe it's a snake, maybe it's something else. And the adult, the prefrontal cortex says, I know that's what you think, but it's just windy.

And you go back to sleep. I was struggling the other night because I had to leave the door open because my wife basically came late and she was out with some friends and she forgot her key. So I left the door open in the hotel room and I'm trying to fall asleep and I'm thinking, oh, maybe someone's going to come in and attack me. Oh, I can't fall asleep. So I had this whole conversation in my head between my amygdala and my frontal lobe. And eventually my frontal lobe went off and I fell asleep. But it was

- Well, not that easy. - Well, sometimes there is a real danger and I think that's important too, right? Like if you're walking through the forest and you hear a rustling in the underbrush, that might be a mountain lion, probably not. But maybe it's just the wind. And the point is, as it relates to our day-to-day decisions, we need to have that adult present because the impulsive choice, the emotionally,

biased choice is most often the thing that's going to detract from our ability to have high quality of life. If you think about why a person, let's say, chooses an unhealthy food,

It's not always that they think this tastes good and this is the decision I want to make. It's often an impulsive choice. And one of the things that's been very clear in this research around the prefrontal cortex, the kind of amygdala connection and the quality of it, and we can unpack that a little bit because really what you want is the bidirectional communication, is that stress seems to take the prefrontal cortex offline.

which is why if you are stressed, you're more likely to eat junk food. Similarly, if you're sleep deprived, this connection becomes a little bit more interesting, right? So it becomes a little bit less concrete. And to that end, it helps to explain why people who are sleep deprived have trouble making healthy choices. They tend to eat a lot more food and they eat a lot more junk food. Oh yeah. And I don't see if I want sugar and carbs. Give me the cookies and ice cream. I've written books all about why not to eat that. I still want it. Absolutely.

I think in the long run, what we're looking at is what are the effects of chronic inflammatory stimuli on kind of dismantling the ability of the prefrontal cortex to stay in control. And that's where it gets really interesting because we're thinking about these insults, the foods that we're eating, the air that we're breathing, the things that are functionally disabling the ability of our prefrontal cortex to make good decisions.

it can help us to explain why we're seeing certain aspects of the world not make as much sense, people not doing the things that maybe we would think they should be doing or that would be beneficial to even the people if you were to ask them. Yeah, it's interesting. You know, it sort of reminds me of this trial back in the 70s that was for this guy Dan White who killed the mayor of San Francisco, George Moscone, and his supervisor Harvey Milk.

And the lawyers mounted what they called the Twinkie defense, which is a very famous legal defense. And they argued that his consumption of basically junk food and Twinkies led to his disordered behavior. And they were able to convince a jury to not convict him of first-degree murder, but of voluntary manslaughter, which is a reduced charge.

So that was really fascinating. And then, you know, we kind of began to look at the data on this. And I know there's more and more research coming out all the time on this, but there was a recent study looking at the link between junk food, sugar-sweetened beverages, and psychological distress. And, you know, there was a study called the Caspian 4 study that took a nationwide sample of 13,000-plus Iranian children, adolescents 16 to 18, and they basically looked at how much junk food they had and what their mental health was.

And it was just striking that there was such a huge correlation, not just between depression, anxiety, and things you might expect, but violent behavior, like, you know, violence. And, you know, increasing junk food led to a 39% increased risk of the odds of physical fighting, 19% increased odds of being a victim, and 55% increased odds of bullying other people. Yeah. So...

- Yeah, let's dive into this just a little bit because I think this is the message that very few people are aware of, which is it's not just that people maybe make worse choices as far as I'm gonna eat this junk food, I'm gonna skip sleep to watch another three seasons on Netflix, I'm not gonna call my mom.

We're talking about real world violent behavior. So one of the biggest studies that was ever done on air pollution looked at the link between a certain air pollutant, PM2.5, and risk for violent behavior. And what they found is, after waiting 10 years to see if these correlations survived, is that PM2.5 exposure correlated with not just any crime, but violent, impulsive crime.

And that's important. This isn't premeditated stuff. What we're talking about is that it changes people's brains, their thinking, such that they're more likely to do things like hurt another person. So there's actually work being done now on questioning what should be done in prison systems to help people with aggressive behavior as far as what nutrients do people need? Because the reality of it is that we've just ignored this completely. We have operated under this assumption that why a person does what they do is a reflection of a psychological construct like willpower.

- Yeah, I think that's right, Austin. You just hit on something huge, which is that we misappropriate the meaning

In other words, we say it's because they're crazy or because they're whatever, not because maybe their brains are inflamed and then they're really acting in ways that are not willful in a sense because they're controlled by this underlying biology. - The Twinkies. - The Twinkies, right, the Twinkie defense. So I don't think people should be absolved of responsibility for doing bad things, but I think it sort of speaks to the massive prevalence of things

that are driving inflammation. I think we hit on two big ones, which is ultra-processed food, sugar, starch, and then environmental pollution, whether it's air pollution, heavy metals,

And I think these are things that we don't really talk about when we're talking about these issues in society. We're talking about a mental health crisis, and it's talked about in asylum. Let's get more mental health care. Let's get more drugs. Let's get more. It's like, no, let's figure out why the brain's not working properly. That's it. There's not a lot of upstream about this. And I totally agree we need more emphasis on how to support people who already have these issues. That is...

absolutely necessary. At the same time, we need to be thinking about why our prevalence rates for these diseases continuing to go up despite the fact that we have solved for technological issues that we never thought we would. And I'd like to bring in one other kind of line of science here. So a lot of recent work has focused on something called maternal immune activation, MIA.

The idea here is that mom's exposure to inflammation while the child is in utero can influence outcomes in children. And so a big study was just published in the last couple of days and it looked at, in essence, mom's inflammatory status when pregnant 24 weeks and then it looked at children's rate of developing ADHD at age 10. So we're talking a long time later. 40% increased rate.

Now, why might that be the case and why does research suggest that maternal immune activation correlates with Tourette's syndrome, with ADHD, with autism, with schizophrenia? It is very likely that the immune status of the mom, the immune state of the mom, inflammatory status, is able to speak to the children by way of placental transfer.

It seems like it might modify epigenetics. It seems like it might speak to microglial cells. So what we're talking about here is not just even ourselves. We're talking about a generational effect of our pro-inflammatory lifestyle that may not be visible until decades later. - So we're talking about what the mom eats

That's it. Her diet and the programming that happens to the baby's epigenome will determine not only the risk of obesity or cancer or heart disease, but the risk of mood disorders, their behavior, violence, aggression. And when you think the fact that 65% of our diet is ultra processed food and that Americans eat about 150 pounds of sugar and 130 pounds of flour a year each,

This is like a national emergency. It is. I mean, this is the stuff that matters most. It's how we think. It's how we act. It's how we feel. I think one of the challenges here is when you look at things through the pharmaceutical lens, the effects of a food, of a lifestyle modification or not, may not be experienced the next day or a few minutes later, right? So if you push epi, you're going to see an effect on the patient pretty quickly, you would hope. But if you change a person's diet... That's epinephrine. That's a drug we use in the hospital. Right.

allergies and heart attacks. - Right, you don't wanna be doing that casually, but the point being, you will see an effect. And if you change somebody's diet, they may not think clear immediately, they may. - Honestly, I would say if you are effective enough by using a big enough lever, in other words, dramatically changing the diet enough,

You'll see changes in literally days. So I have seen that. I guess the point I'm making, though, is when we're looking at these global factors, this is where it becomes challenging because we would say, oh, well, as an evidence-based intervention, if we give somebody a bowl of kale as opposed to a hamburger, we didn't necessarily see their depression alleviate overnight. So let's just stick with what we have.

But if you look at longer term data, for example, the Mediterranean diet on rates of dementia, on rates of depression, it's pretty profound. The challenge is how do we get people to care enough to implement it? How do we decrease the barriers to making those the norms in our diet? And I think this is where

our food industry has us in a really bad spot. Because what they would say is, well, everything in moderation and give people the opportunity to choose what they want. Now that's fine as an idea. - Just have one line of cocaine or one shot of heroin on me. - Right, everything in moderation. So you can have your hamburger.

Don't do that. So you can have your hamburger, you can have your soda, but then you have to make sure to exercise. And I like the, it's part of a complete breakfast, right? You've seen this for the cereals where they have the cereal, but then they have the fresh fruit and they have five pounds of fiber on the side. The problem is that we believe in this idea, this myth, that it's great to promote freedom and that you can do that through letting people have freedom of choice. But the reality is,

You don't. Well, you don't have choice unless you understand, right? You can't make a choice unless you have the knowledge to make the choice. And you don't have access.

access and knowledge even in terms of the food labeling, food marketing, advertising. It corrupts our understanding. Unless you're a PhD in nutrition and even then it's hard to understand a nutrition facts label or an ingredient list for most people. And in other countries they don't have this problem. They've eliminated all the advertising for kids on junk food. They've eliminated all the cartoon characters in Chile on the Frosted Flakes. There's no more Tony the Tiger. They've gotten rid of all junk food in schools. They've

put front of package labeling on big stop signs that say, don't eat this. This is going to kill you. And essentially you can eat it, but it says, don't, this is really bad for you. Right. And so it actually changed behavior and it changes what people choose because they have the right information. We don't have that. I'm actually working in Washington now on a food labeling effort to change food labeling so we can protect our children and have a clear grading so that we know what's in the food and people can actually understand it.

That's so important because what you're bringing up is the significance of defaults. And this is an aspect that requires policy, it requires higher level intervention. We do things that are easiest to do. And at scale, that plays out. So many researchers now have been looking into how do you make the healthy choice easier to make at companies like Google. So there's a stoplight system. This food is green, this food is red. And this stuff is really important because it's often the subtle things that have the biggest effect. I would just say going back to what you described as far as the

cartoon animals, we won't name any of our friends, but you know, we know these animals on the boxes of sugary cereal. These things have an impact. There is a reason that they're there. And when you look at an adult's preference for cereal decades later, it is consistent with what they were given as a kid because of some of this fun association they had. The United States is one of only two countries though that allows direct to consumer pharmaceutical advertisement. So we're hitting people on both sides of the spectrum with the belief again, give people freedom of choice.

But it's not actually freedom of choice when the defaults are structured in such a way that you're almost certain to make the wrong decision. Yeah, I'd be fine if they had, you know, junk food ads on television, the Super Bowl. But at the end, just like pharma ads, they said, if you use this thing, it will kill you and cause diabetes and heart attacks, early death, stroke, depression, dementia, Alzheimer's. Like that, I'd be fine with that.

Because that gives people joy, right? It's actually information, education. I actually have a theory about why Washington is so screwed up. I've been many times in Washington, walked through the Senate, walked through the House, been there, had to eat sometimes lunch there in the cafeterias where the senators eat and the congressmen eat and all their staff eat.

And it's essentially a cesspool of junk food. I mean, you know, monster size sugar drinks, processed food, and also all the fast food outlets are there. So, you know, McDonald's, Burger King, Pizza Hut, they're all there. And that's what they're eating. And I'm like, well, that's what people are trying to like make our country better and make decisions. And their brains and their bodies are all...

- So two things, one is-- - Hyped up on this craft and their brains are all inflamed, no wonder their emotions are inflamed. - So I think people forget the brain is built out of nutrients from food. It's not like we can take carbon from the atmosphere and sequester it. We have to create brains, the rest of our body as well, out of the molecules in our food. So if you're literally building your brain out of junk food, that's going to have an impact on how you make choices. So the other thing I was just gonna say here, which I know you're incredibly familiar with,

Yeah, it's miserable that at the highest levels, the people who are in charge of our decision making are powering their bodies with junk. But this happens in the hospital at an even more extreme level. Oh, totally. So I know we don't have to get into this, but I remember being on my residency interviews and being at some very prestigious centers that were actually very close to where we are now. Yeah. And going into the cafeteria and seeing that the quality of that food was worse than what you get at kind of a gas station restaurant. Yeah. And...

It just seems like the doctors and the nurses and the staff are all eating. And the reason is because we assume that it doesn't matter that much. Right. Just we'll wait. And when things get bad enough, we have drugs. Let's not focus on things that maybe are not worthy of our time and money. And it's so backwards. So bad. Not to mention what you feed people in the hospital. No, it's terrible. I actually, two little anecdotes. One, I used to work in the emergency room and I would take this night shift on time. I would work from like, you know, I don't know, 11 in the morning, 11 at night to 7 in the morning.

And I kind of missed the cafeteria hours because they were only like 8 to 9 in the morning, 12 to 1 at lunch, and then 6 to 7 at night. The only thing that was open from like, I think it was 6 in the morning till 2 in the morning was McDonald's. Of course. And at Cleveland Clinic when I started working there, Toby Cosgrove essentially tried to get McDonald's out of there. Couldn't do it because it was a long-term contract. But literally the day the contract expired, I was there.

And the McDonald's was there one day and you walked in the next morning and it was gone. Like you literally had it boarded off and completely shut down one night. But that should be illegal. I mean, I think it should be a law. Like you can't smoke in a hospital. Or just be honest. It's not about health. But you can't smoke in a hospital. Right. Why should we be serving food that actually kills people in a hospital?

what you're saying makes sense. I think if you were to actually take a blanket statement and say, this is the place where we're going to optimize for healing, then that is true. But as we know, that is not necessarily the case in all institutions in that the

for a number of reasons. There are wanting to give people access to freedom of choice. And that, I think, is part of the illusion that's been created, which is we're not doing anything wrong because it's you that has to pull the trigger. We're just creating the food. We're just creating the scenario. And you have to be the person to come eat it. But if your brain is dysregulated, it's hard to make the right choice. Right, which, by definition, if you're in the hospital, so...

I mean, we could talk about this a little bit. One of the best instances that I saw early on of how inflammation impacts the brain was in the ICU, where up to 70% of people are experiencing delirium, right? Delirium is a very common thing in the hospital. Why is that happening? Well, it actually correlates with levels of inflammation in the bloodstream. So as you increase inflammation in the context often of these kind of severe infections and metabolic dysregulation,

your thinking gets messed up. So we see this in the hospital. We have the connection with inflammation and people's cognition getting worse. And then we think about what are the lifestyle variables that map onto inflammation. So we should be advocating for a Mediterranean diet, healthy menu in the hospital. There are some breakthroughs that I've seen happening around the country, but by and large,

And that doesn't mean pizza and pasta. Right. Because that's Italian. That could be Mediterranean. You mean whole foods, lots of vegetables, nuts and seeds. Foods your grandparents would recognize, however you want to describe it. You're exactly right. I don't think there's a universal definition of Mediterranean diet. Real foods. Yeah, real food. And I think speaking of real food and how important that is, we've talked about how our ultra-processed diet, sugar,

starch, all that drive inflammation in the brain. We're going to get to how the gut plays a role. We've learned about how environmental toxins, whether it's air pollution or plastics or petrochemicals or heavy metals, all can interrupt the brain's function and drive inflammation.

I mean, we know this, you know, the felt maker, hat makers back in London in the 1900s, 1800s were all crazy because they used mercury to make the felt hat stiff. And so that's where the Mad Hatter came from in Alice in Wonderland, right? And some heavy metals for sure.

But there's a flip side to it, which is there's an antidote. And this one study really compressed me. It was a study of young adolescent girls who ate more sugar and starch and junk food. And the more they ate, there was a 1,400% increase in aggressive behavior. Now, for those listening, if in medicine you see a 20% or 30% increase

Delta change in something, that's like a blockbuster. So statins reduce the risk of heart disease by 30%. Wow. Blockbuster drug. We're talking about 1400% increase. It's not something that's unlikely to be correlated. And what was then more interesting was when they looked at the case control study, if there was more fiber in the diet, more omega-3s, more vitamin K, there was a lower risk

association with aggressive behavior. And this tracks against other studies that I've talked about and that I wrote about in my book, Food Fix, or in prisons, for example, where they took prisoners who were violent in prisons

and they gave them healthy food, there was a 56% reduction in violent crime. If they added a multivitamin, it was an 80% reduction in prisons. They did this with juvenile detention centers where they took kids who were eating junk food, they gave them whole food, and they saw that a 97% reduction in bad behavior, a 75% reduction in restraints,

and 100% reduction in suicides, which is the third leading cause of death in teenage boys. So that's massive data. And yet to me, this should be things that's shouted from the rooftops that all academic medical centers should be implementing, that policymakers should be paying attention to, that we should be really getting to the root of this mental health crisis. It's not just that it creates more polarization and disruption in society, but the depression, the anxiety, the things that go along with it

are huge impacts on our economy. When you look at, there was a macroeconomic study looking at the cost of chronic disease, and it was estimated it was gonna cost $95 trillion

which is a lot of money. That's like, I think, you know, our GDP is like 20 trillion or something. And it was $95 trillion over 35 years. And the number one contributor, because they measured direct and indirect costs, not just direct healthcare costs, was loss of productivity and disability and dysfunction from depression. Yeah. Well, I don't think that it's universal, but what you reference as far as behavior is a reflection of

this outdated ideology which is that behavior is a reflection of who a person is and the best ways to change behavior are going to be reward and punishment. And that's it, right? It's basically you are who you are. If you do something wrong, we're going to put you in your room, right? We're going to allow you to have time to reflect on this so you don't do it again. And

Historically, this doesn't really work well in certain cases. For example, drug recidivism after people are punished for using a drug is pretty high because it turns out that the reason people were using the drug was to feel better and that when you made them feel bad in jail and you didn't necessarily give them any of the things that were necessary to improve their quality of life, they will go back to using these molecules again. So it's this idea that behavior is a fixed reflection of who a person is. What we're talking about with this neuroinflammation

can be controversial because what we're saying here is you are dynamically changing moment to moment. So in your body, your immune cells turn over as a reflection of total number every couple of months. In your brain, you are growing new neurons all the time and you're more importantly changing the strength of the connections between those neurons all the time. Since your thoughts, your feelings are a reflection of your neuronal state and of your brain state, that means that you as a person, as an identity, as a belief system are changing moment to moment.

when you appreciate what immunity means to that, because immunity is a master system that modulates the strength and number of the connections between your neurons, changes how you think, changes how you feel, you realize you're kind of operating on the core operating system of what makes you you. And that can be a scary thing. I think it's opportunity.

Because we don't have to sit and blame people for the way that they are. We can be curious about, say, what is happening with you right now? There's some low-hanging fruit that you can change, that every person can change as it relates to optimizing their overall immune health and improving their brain's immune balance. And if you do those things and you feel less aggressive and you feel less impulsive and you feel happier and you think clearer,

I mean that's kind of all of the things that we would define as who you are. Your interests change. There's a really interesting study. You're nicer to your neighbors. Yeah. You don't have road rage. Right. So an interesting study looked at microglial cells and it found that it might predict people's personality traits, meaning the state of microglial cells.

This is really fascinating stuff because we're talking about one of the areas in which you kind of change who you are. So not to go too much on this tangent, but psychedelics seem to increase trait openness, right? So open-mindedness, these are things that can happen and really in some ways should be happening. Not saying that specific to psychedelics, but changing who we are and updating our prior assumptions is key to what makes humanity unique.

right and when we get more and more locked into patterns of thinking which i believe neuro inflammation does yeah we lose our best chance at actually participating in this life for all it's worth and kind of the uh the cost of that the fringe cost is that we're more likely to allow this world to fall into chaos and to allow the climate to be destroyed these are things that are where's the grown-up in the room in the world that's it that's it we've got to be uh

thinking about what are the things at scale that will promote more adult level thinking. And one of the things we can do is optimize our brain immune state, neuroinflammation. It's so important what you're saying, Austin. I want to get into the details of how do we regulate neuroinflammation. But before we do, I want to hit on one more key point that you've kind of touched on a little bit, which is the gut-brain connection and the microbiome.

And I just, I want to start out by a little anecdote or anecdata or end of one trial, which was a little girl I saw years ago who came to me because her mother didn't know what to do with her. And she was

I had written my book, Ultra Mind Solution, which was about how to fix your brain by fixing your body first, essentially dealing with the inflammation by changing your diet and lifestyle. I wrote this book 15 plus years ago. It was way ahead of its time. It's still, you know, I was talking about the gut and the brain and all this stuff way back then and no one really talking about it.

And this girl, you know, I just said, I don't know what's going on with her. She's this beautiful little girl, but she was so violent. She was attacking her sister all the time. She was nine years old. She was violent in class. She was kicked out of class multiple times a day. On the bus home, she'd be kicked out the bus. They have to stop the bus, you know, a dozen times on the way home. She would be ripping pictures of her family, like ripping her sister out and just like really crazy behavior. Yeah.

And, you know, they talk to the therapist, they do this and they do that. Nothing helped. And I'm like, I don't know what's going on, but let's just have a look. And so I just screened her for her gut health and looked at her urinary organic acids and looked at the microbiome and turned out she had severe elevations of biomarkers for bacterial overgrowth in the gut, for yeast overgrowth. So I literally gave her an antibiotic and an antifungal.

And like, boom, overnight she was a different person. - Yeah. - Like a perfectly behaved, sweet little nine year old girl. And that was when the light bulb went off in my head of like, holy cow, like what else is going on here?

- Yeah, and so it's really been this incredible treasure chest we've been able to open of understanding the link between the gut health and everything in the body. But we're gonna focus on particularly the brain right now and neuroinflammation. So can you unpack for us how our gut and our microbiome and gut inflammation and leaky gut and leaky brain are all connected and kind of unpack that story for us 'cause I think it's really important because there's so much we can do to optimize our microbiome.

I think it's a really incredible area of research and there are certain domains that have overlap between conventional medicine and kind of the wellness domain and gut health is one of them because it's interesting to my friends who are practicing conventional gastroenterology and it's interesting to my friends who are non-medical but think maybe this is a way to get healthier.

What I first saw as it relates to this, and I think you've spoken about this on previous podcasts, is hepatic encephalopathy, right? This is an instance in which people, for one reason or another, develop liver failure. They build up these nitrogenous compounds, and basically they get altered. They get loopy. They kind of lose themselves in this haze of- They have hallucinations. They get delirious. 100%. They're brain fogged. They're not-

They're getting out of bed. They don't remember who they are. And the reason for it is basically the absorption of these nitrogenous compounds as a reflection of what is happening in the gut. And the conventional therapy for this- The toxic metabolites of gut bacteria that are getting absorbed and poisoning the brain and causing the brain to be crazy. Causing us- So this is-

This is a direct connection between the gut and the brain because the interventions for this are flush out the gut or give antibiotics to kind of re-regulate the gut. Those are the conventional therapeutics. - Yeah, you give neomycin to clear out all the, it's like a nuclear bomb for all the gut bacteria. - Right. - And then you give basically a plunger called lactulose. - Exactly. - Flushes the gut out. It's like a super laxative. - Yeah. - And all of a sudden they wake up, it's like boom.

Right. And you track improvement by how many bowel movements they've had, how many bowel movements this person had, because the goal is to flush out all of those toxin producing bacteria so that they don't absorb all of these nitrogenous compounds. So they have shit for brains is basically what you're saying. Again, official diagnostic code there.

The point is there is a direct connection between the gut and the brain in that sense. There's research, as you know, going back nearly 100 years looking at what had happened as far as when you removed parts of the gut that was being done for a variety of different reasons. The point here is we've known for a long time that there's something connecting the gut with the brain, but we've only more recently started to get specific as to how that happens and what we can do to modulate. So a couple of the statistics. For

For a few years, we were quoting-- By the way, what you're saying about hepatic and cefalophy, that has been something we've learned forever in medical school. Every traditional doctor knows this, and yet,

it doesn't translate into the rest of their medical practice that the gut could affect the brain. Right. I think that's accurate. I think this is the instance of knowing that there is this connection. We have a specific protocol in place, but by and large, you don't think about it. Generalize. No. Right. Exactly. So going back to what we now know, I think it is fair to say that the gut brain connection or really just gut health in general is revolutionizing the way that we look at our own health.

We know that the gut has, I think the most recent update is 39 trillion microbes, the majority of them clustered in the large intestine, which is important because from a bacterial perspective, the majority of those are bacteria. That's about the same number of cells as we have in our bodies. And microbes have 10 times the DNA. So as a relative ratio, we're more bacteria than we are human, which is kind of a crazy thing to say. We're just basically a walking organism.

carrier for all the bacteria in our guts. I think that's true. And there was a recent study that I was discussing with our friend Jeff Bland that suggests that social transmission of microbes is a big explanatory reason for why we think and act the way we do. So wait a few years and you'll find out that it's not about us. It's about the microbes living on it in us that are actually defining our interactions. But to go back to this,

What we now understand is that the gut and the brain are in constant bi-directional communication. So what happens in the gut impacts the brain and vice versa. There's a couple of pathways that have been isolated. Top down, bottom up. Right.

I guess bottom up being more specific in this case to the gut to the brain, but sure, both ways. And again, I think we will learn in the future that maybe this part is not in as much control as we thought. So the gut can interact with the brain through the bloodstream, through molecules that are created in the gut that get into the bloodstream, go up into and either bind to your receptors on the blood-brain barrier or go through the blood-brain barrier. Then we have this whole bypass system, the vagus nerve, right? Wait, so you just slow down. You just basically said that

Molecules from poop, from your bacteria in your gut, get absorbed. Right. And then go up into our brain.

- And get absorbed into our brain and are communicating with our brain and regulating our brain. - That's it. - And causing inflammation in our brain. - Or helping to suppress it, as in the case of short chain fatty acids, but you're correct. The idea is that on the pro and on the con side, so the bad ones, we would think about lipopolysaccharide being the best example. This is a component of a bacterium that when absorbed is a potent regulator, increases inflammation. - Toxic.

It is a toxin it's believed to mess with basically everything in our bodies, but it seems to specifically activate microglial cells. It binds to a receptor called the toll leg receptor four, which maybe it's just interesting trivia, except for you realize the microglial cells are listening for what is happening in your gut to be able to make decision.

And I'll just say one more thing. Looking at animal models, we know that microglial and neuronal development is in part contingent on what happens in the gut, which means that our gut helps to teach our brains how to kind of grow and establish themselves.

Really, really interesting stuff. So what happens in the gut absolutely influences the brain. One way is through the bloodstream and the other way is through the vagus nerve because the vagus nerve runs all the way from the brain down to the gut, down to the majority of the gut I should say, and is mostly fibers that carry messages from the gut to the brain as opposed to the other way around. So these are two of the most important pathways. And the other thing I'll just lay in here which I think is really key to this conversation

The gut is where we have a reservoir of the majority of our immune cells. And the reason for this is because our immune system is not just a defense system, but it is designed to learn from what is happening in the outside world and transmit those signals through the rest of our body, including our brain. So your immune cells live just below your gut lining and they actually send up little arms to grab pieces of food to eat.

to interact with bacteria, and they take that message down. They change the way that they function, and they can actually send those signals through the rest of the immune system, and in doing so, influence the brain. So this is a constant bidirectional communication. And this is just straight-up regular medicine science. We're not talking... This is just science. This is nature, kind of high-level papers. This is well understood now, everybody. It's not kind of some quack...

side hustle we're doing here about poop and the brain. It actually is really deep science. Right, this is established. It's not being used in clinical medicine at all, really. It's just sort of like, okay, well, we get it now. Now what? No, because most doctors have no idea how to normalize the gut bacteria. Because like you said, they're not all bad. Bacteria are good. They do so many good things for us if we have the right

collection of bacteria, but if we have noxious bacteria, they produce more of these toxic compounds, they produce more lipopolysaccharides that are then absorbed, and it creates this cascade. And it doesn't just affect the brain. So lipopolysaccharides also will cause you to be more insulin resistant and diabetic, even if you don't change your diet. So literally, and these experiments just blew me away. I don't know if you've read those, but like an animal model where they would literally take the poop

of a fat mouse and put it in a mouse that had a sterilized gut, it was a skinny mouse, and then the skinny mouse would have those bacteria and eating the same amount would gain like 57% more weight. - Right, there's similar data for depressed humans and to mice. It's absolutely fascinating.

I think just to back up your problem-- - Maybe we're gonna treat depression with a poop transplant? - It's not out of the range of possibilities. - Or treat obesity with a poop transplant? They've done that with that. - These are things that are happening. These are things that are being considered. Just to take this one step back, the idea which is a very basic idea that most people probably at this point in the conversation would agree with is that what we eat influences our brain function. If we believe that, which I hope we do, then we could ask, well, what should we eat to positively influence our brain function, our brain immune balance?

When I did medical training, not all that long ago, there were really only two domains in which we connected diet with brain health. One is deficiency. So if you were eating the tea and toast diet, you could get a B1 deficiency. You get a B12 deficiency. And these are conditions that we learned how to treat. So if an alcoholic came in, we give them thiamine. These are things we knew. It's called Wernicke's encephalopathy, right? Which is that kind of insanity you get from actually being vitamin deficient from being an

- Metabolic. - Exactly, exactly. The other piece of this was the metabolic component. So we knew that if somebody's blood sugar dropped below 50, for example, they may go into a coma. That's not a good thing. That is a real problem. If they came in with diabetic ketoacidosis or any state of really high blood glucose,

patients might have a higher chance of being altered, mentally unstable in the sense of delirium and otherwise unsafe. So we knew that blood sugar had a direct correlation with brain state at the extremes. Beyond that though, there was nothing else. What is the diet a person should be eating? And more specifically, are there customized nutrients, patterns of eating that we should be using to program our brain for better health? So we were so many steps

away from the gastrointestinal tract, unless somebody had a functionally disabled GI tract and they had to think about putting in a tube or doing an IV feeding. But that was literally it. So what we're saying is the science has gone so far and there's so much that we can glean from these microbiome and gut studies that really should be implemented today for brain health based on the research being published in literally the top journals on earth. - Yeah, well there's now a whole field of what we call psychobiotics, which are,

probiotics that have an effect on mood and depression, anxiety, sleep. I'm trying one now, which is basically a sleep probiotic. It's supposed to increase deep sleep. I don't know if it's working. I'll tell you later. But it's interesting that there's these compounds starting to be like customized probiotics to actually regulate these various mood and mental health states.

Again, this all makes sense when you understand the pathways involved. There's a quote that many people bring up, which is the majority of your serotonin is produced in the gut. Now, that's nice. However, serotonin in the gut doesn't cross the blood brain barrier, but it can interact with the vagus nerve and vagus nerve signaling can change the brain. And also there are other metabolites like tryptophan, which is the precursor that can be produced in the gut and then can get into the brain.

So there is absolutely a correlation between what happens in our gut and our brain state, both in terms of cognition and in terms of things like sleep. One thing I'd just like to say on that front is,

If we think about what actually induces sleep, there are a number of variables. We think about adenosine and other things happening in the brain. But inflammation was actually one of the first variables that was studied as what drives sleep, a hypnotoxin. Basically, they looked at animal studies and they derived kind of an immune marker that predicted sleepiness.

And it means if they're more inflamed, they're more likely to want to sleep. So that's part of it. And it can help explain why people who are sick tend to be very tired. Ever wonder why that is? It's interesting when a person is incredibly inflamed in the context of something like sepsis.

their immune system might actually be eating up 40, 50% of their energy reserves in their body. So this isn't, you know, kind of rocket science. If you don't have energy, ATP going around, you're probably going to be a little bit more fatigued. But it does seem like the immune system and sleep are really closely bi-directionally interacting. And so if the gut influences the immune system, the immune system influences sleep, then the gut microbes seem to be key to this process. - Yeah, it's so important. So let me sort of summarize a little bit, and then we'll get into like, what the heck do we do about neuroinflammation?

So clearly we're in an epidemic of inflamed brains and the drivers of it are our diet, lack of protective foods, which we'll talk about in a minute, too much ultra processed food, particularly sugar and starch, and environmental toxins, which are ubiquitous. All the petrochemical toxins, heavy metals that are everywhere.

air pollution in our gut and our gut microbiome. And the disturbances in that because of our lifestyle and diet. You mentioned a few of the things that drive neuroinflammation like lack of sleep, stress,

lack of exercise. So these are all things that we actually have a fair bit of control over. We can't control air pollution particularly, and maybe we can get an air filter in our house, but a lot of these other things we can control. So those are the things that seem to be driving the neuroinflammation that's leading to this sort of epidemic of mood and behavior disorders and neuropsychiatric and neurogender disorders, even neurodevelopmental disorders.

What is the right approach to take care of your brain? You mentioned there's no preventive neurology, right? Not really. There's preventive cardiology. There's no preventive psychiatry, but there should be. So what does that look like? And how do people start to prioritize those things we know that are things we should be avoiding or things we should be adding in to optimize our brain health?

I'd start with kind of a psychological construct here, which is you and I have talked about lifestyle modification for health for many years, and many people listening, watching will have heard about these things before. I've been talking about it more years than you've been alive, Austin. This is probably accurate. It's probably accurate.

The crux of the matter is something that we've discussed, which is people change when there's psychological pain. And I think that's the key to it. And it's to find an energy within yourself that's going to fuel this. Because the reality is any of us could do a diet for a few weeks. Any of us could join a gym for a few weeks. The core constituent elements of lifestyle modification are well known to most people. And I think, at least for me personally,

It's that I've had two grandparents die of Alzheimer's disease. I have seen so many patients and people I know suffer from mental health conditions and neurodegenerative diseases, and I refuse to accept that that's the best we can do.

And I think if we have that within ourselves, which is the understanding that if you do not make changes, you will, by the law of statistics here, law of probability, wind up with at least one chronic disease on at least one medication and an incredibly high risk of developing Alzheimer's disease and a mood disorder. Now, I'm not trying to say we can prevent all of it, but I'm saying that for me, I am unwilling to accept the status quo.

- Yeah. - So if that is for you, if you're somebody who's saying, "No, that's not me. I want to do better than average," then you start to gain some actual energy behind making some of these changes. And I think that's the really important kind of driver of the- - People don't even know that they can make a difference or that those things are connected. - And that's the next piece of it, which is to know that by simple lifestyle modifications, you can dramatically decrease your risk for brain inflammatory conditions

like dementia, like depression, and a host of these other ones that we've discussed. So let's go through some of these things, right? I think diet is probably the one that most people are interested in hearing about, and for good reason, because we actually have a lot of choice over what we eat. So we may not be able to modulate the air quality each day. We may not be able to get as much exercise as we want, but we have to eat, and therefore we can change the quality of the food that we eat.

By and large, based on the research that I've reviewed, the best diet for preventing neuroinflammation and promoting brain health is some variant of the Mediterranean pattern diet. So the Mediterranean or its close cousin, the MIND diet, these are not complicated things, and I want to stress that. These are not highly restrictive diets. They're not fad diets. These are diets that incorporate a wide range of primarily plant-based foods. There's fish, there's some poultry, but it's really getting a wide range of plants.

And these are things that are rich in polyphenols, these molecules of which there are thousands found in a variety of plants across the planet that seem to be correlated with better cognitive outcomes and especially correlated with better immune outcomes. So we're talking colorful fruits, vegetables. We're talking things like spices. So herbs and spices are actually some of the most concentrated sources of polyphenols. These are natural anti-inflammatories. Exactly. And we also know coffee, which is one of my personal favorites for reasons beyond the polyphenols, but the polyphenols help.

Wine has some. We could talk about that. I had too much of that last night with you, Austin. I didn't sleep as good as I'd like to.

There you go. It's a cost benefit analysis. It was really good wine. Wow. I only have one when it's really good, and I don't usually have it that often. But when I do it, I like it. It was a good wine. It was a good wine. So again, it's just eating real foods most of the time. I think there's a lot that can be said for substitutions. And obviously, you know, we're doing this work with this Himalayan tartary buckwheat because it is a better version of what most kind of conventional grains are. It happens to be a lot higher in polyphenols than almost any flour on the market.

So it's really kind of concentrating a diet that is rich in real foods. And I know, and I've listened to guests on your podcast and other podcasts, everyone has their slant on the ideal diet. I think what you talk about with the pegan diet, what you talk about with eating real foods, this is the key to it. And this is the benefit here is that this is the diet that is most strongly associated with lower levels of inflammation. There was actually a study just came out

166,000 people, they followed them for multiple years and what they looked at was basically rates of people developing dementia. So they looked at how anti-inflammatory was their diet, was it a Mediterranean diet or was it a more conventional diet? What they found is that people who ate the anti-inflammatory diet, the Mediterranean diet, lower risk for dementia and

bigger hippocampus, which is the memory center of the brain. So it doesn't have to be super complicated stuff. It doesn't even have to be super expensive stuff. It's basically eating real food most of the time. So that's my kind of dietary slant. And fiber too for the microbiome, prebiotics, food.

I think the fiber comes along with the prioritizing real minimally processed plant-based food. I do think that we're learning more and more. I mean, a study just came out showing that fiber consumption inversely associated with all cause mortality. This is, it's good stuff. It's real stuff. We can talk about mechanisms, but yes, fiber prioritization comes alongside with eating foods that people have messed with the least, specifically plant-based foods. Don't eat, that's a good one. Don't eat food that's been messed with. Yeah.

Unless it's by an amazing chef, I guess. Right. It's like a tomato from the plant. Okay. Right? If it's an egg from the farm, okay. Can you name it? Right. My joke when I used to speak at churches when I was doing this work with faith-based wellness was the rules for eating are really simple. If man made it, leave it. If God made it, eat it. You know, did God make a Twinkie? No.

Leave it. Did God make an avocado? Yes. Eat it. It's pretty simple. Anybody can understand that. Yeah.

- Yeah. - Food made by plants, not in plants. - That's right. - Yeah. - That's right. So food is such a critical aspect of this and a critical aspect of immunomodulation, immunorejuvenation. And now, you know, one of your day jobs is the managing director of Big Bold Health, which is an extraordinary company that I am an advisor to and investor in that's been founded by my mentor, Jeffrey Bland, who's the father of functional medicine.

And it's a long story we talked about on the podcast before, but this particular plant, Himalayan Tartary Buckwheat, has particularly immunorejuvenating anti-inflammatory properties. And it comes from a plant that's grown in extremely difficult circumstances, high in the Himalayas, in terrible soil, at high altitude, in cold weather.

And it forces it to be really robust. And the way plants become robust is they build defenses. And the defenses that plants have are these phytochemicals. So these phytochemicals are found in extraordinary numbers and levels in this particular plant. Now you can make pancakes out of it, which is great. But there's a new, you can take it as a concentrated supplement, which I do, and I recommend it. It's got quercetin, bioflavonoids, many other things.

But there's a new product that's come out of this and it's all through regenerative agriculture. This plant is grown in America now. It's Himalayan Tardy Buckwheat Sprouted Powder, right? What's it called? Yeah, sprout powder. Sprout powder. And you can go to bigboldhealth.com and check it out. But it's really kind of an amped up version of the Himalayan Tardy Buckwheat.

flour and it's something you can, it's sort of already pre-cooked, sprouted, so you can eat it raw. And I throw it in my smoothie. My wife puts it in her coffee, like blends it up in a little Nutribullet. So tell us about how that plays a role in modulating inflammation and how that can be an adjunct to some of the dietary things you're talking about.

I think that the core idea here is the idea of food is medicine, which is the idea that food can help people to heal. And if you believe that, then certain foods are better than others. Certain foods are the opposite. Certain foods are poison. They're taking away from the quality of your life, the quality of every aspect of what it means to enjoy our existence. And certain foods are able to enhance that.

I'm training as a conventional medical doctor. You know, I learned things about diet. I learned things about how to make recommendations mostly through the Institute for Functional Medicine and other similar programs. Hearing you speak actually a long time ago. Within this field, I learned that in order to scale out nutrition based solutions for people, you have to actually pay attention to how that food is grown, who is growing that food and how you get food to people. So as much as I would like to say. And how it tastes.

Yeah, absolutely. Well, that's a big piece of it. So as much as I like to say, here's my top five foods at Costco, I don't have a whole lot to say about the quality of the Costco organic olive oil, which I think is actually pretty high quality. But point being, I'm not necessarily involved in that supply chain. So at Big Bold Health, Jeff has decided that he wants to really take a more solid role in participating in that entire process. So we have these farms in upstate New York.

We're inoculating this plant with kind of fungi and bacteria in order to promote a healthier soil microbiome, which

is something i've been learning about more recently it's kind of an interesting thing the soil itself has a microbiome speaks to the plant and actually by way of that bi-directional interaction with kind of the plant brain and the soil brain the microbes changes the amount of the plant's immune chemicals these polyphenols yeah so we grow it in new york where it's colder where we have higher levels of these polyphenols to start with then we inoculate it to further increase it

Then we grew this plant and we've been kind of putting this tartary buckwheat, this Himalayan tartary buckwheat into the market for a couple of years. And one of the things we've heard is that people wanted a more convenient version of it. So we said, how can we make it more potent and how can we make it more convenient?

So we found this incredible research, this literature showing that when you sprout foods, it actually can increase levels of a number of different minerals, vitamins, and also certain polyphenols while decreasing some of the trouble that people have with digestion when they might be eating a non-sprouted food. Yeah. And I had messed around with sprouted foods as I was younger. By the way, buckwheat is neither wheat nor grain. It's a flower. It's a fruit seed, actually, of all things, which, again, very confusing name. It's not a wheat. It's not a grain. Yeah.

So we partnered with this group and we started sprouting it and we measured the levels of these polyphenols, things like rutin and quercetin, and we found that they were on average around four times higher in the sprouted powder, which is super convenient because actually I've used your pancake recipe several times.

And it's great, but it's kind of more of a weekend, Sunday morning type thing. You're not just going to whip it up on your way to the office. So what makes the Sprout Pattern unique is that it's, first of all, tastes a little bit less bitter because of the way that it's sprouted. And it's just super convenient. You can travel with it. You can put it in your smoothie. You can put it in your coffee. I guess it's kind of like a Sprout Matcha Latte kind of thing. But it's been fun. It's great. Yeah, it's amazing. And the reason I brought it up is because, you know,

it's sort of one of those compounds uh in our in our food supply that can be used to modulate our immune system right regulate their inflammation and there's obviously many others but i just sort of wanted to highlight that and then of course you know there's other things we're going to have to do for our brain right now you're done you got it what that's it that's it no we have to sleep we have to deal with stress we have to exercise yeah all that's a given uh

And we have to fix our microbiome, right? And part of the sprout powder is it contains a lot of fiber that helps with the microbiome, right? That's right. And what makes the whole tartar buckwheat story interesting and my work with Jeff interesting is that we're trying to actually study this in a more systematized fashion. So there's a study that I know you're aware of where we're actually looking at what happens when you give people the polyphenols in Himalayan tartar buckwheat and you measure their immune system. And specifically, you measure the epigenetics of the immune system.

It's complicated stuff. But it is some of the first research looking at if we believe in this idea of food as medicine, how? How does food actually heal? We have for years operated under this antioxidant paradigm where certain foods have more antioxidants than others. It hasn't necessarily panned out.

So what we do know is that certain diets correlate with certain immune states. What we didn't know is why. And I think the mechanism that we're looking at here is through epigenetics, by changing the way the DNA is being used. And that's what we've been looking at in this study. And at least in the data we have so far, it looks like when people's immune systems are aging faster, so in the group of people who are kind of gaseous,

getting older in their immune system more than others, that it actually slows the rate of aging when people are taking these polyphenols that are found in Himalayan charcuterie buckwheat. So this is early stuff. Early research. So I'm basically reversing biological age to epigenetic age. Right. In the right population. And again, early stuff. But the crazy thing for me, at least about this, is we are starting to get to this core mechanism of food is medicine. Okay, but how?

and why and if we're literally changing the way our dna is being used through the food that we eat think about the possibilities this has been looked at in certain cancer therapeutics and we're starting to look at it as it relates to just general health meaning when people eat certain foods you are changing the way your dna is being used and in doing so are going to modulate a person's risk for a host of issues

and potentially use it to upregulate pathways linked to better health, which is what I'm excited about. Let's not be all about disease. Let's talk about how to get people to enjoy life. Right. It's the whole concept of not just anti-inflammatory, but immunorejuvenate. Right. Which is how do you rejuvenate? Because that's what I care about. I don't have any diseases, but I want to optimize. I want to rejuvenate. I want to feel better. I'm not in a disease state, but I want to get into a better optimized state.

And so that's a whole other conversation. I think, you know, I just want to sort of close by sort of pointing out that, you know, this research is backed up by a lot of evidence, this whole concept we're talking about. And there's randomized human clinical trials, for example, the SMILES trial, they looked at...

basically diet and antidepressants. And it was basically as effective, if not better than antidepressants, if you ate a whole foods diet. The finger trial looking at Alzheimer's, a multimodal intervention using lifestyle interventions, dietary interventions,

optimizing biomarkers, actually reverse cognitive decline in Alzheimer's patients with something that doesn't actually happen. There's no drug that does that. So we're basically looking at these interventions, which maybe seem like soft or not real medicine. They actually are the most effective medicine.

I'd also say this is your best chance at living a healthy, happy life. This is it, what we've got right now. It's not like there's some drug that is going to come and save you. Drugs are really great when things go wrong enough to justify drug use. But by and large, the way that conventional pharmaceuticals work is they slow the rate of decline. You're already on the slope. You're already on the slippery slope. You may not slide as quickly. So what we're talking about here is preventing yourself from getting on that slope in the first place. And that is such a powerful message because...

So much of my work, I seem to interact with people who are a little bit older in further years, and there's so much that they can do to improve their quality of life. But I really want to reach out to younger generations. I see so many people my age and younger who haven't yet started to prioritize their brain health.

And inevitably they all follow the same kind of continuum. They ignore it until it gets so painful that they have to do something about it. And I don't want people listening to be the person brought into the ER or brought into the clinic by their partner when they're 70 years old and everything's already gone wrong. This is your best chance to seize health today. So I just hope that more young people take that to heart. Yeah. Thanks so much, Austin. This is such a great conversation. I could talk to you for hours, but I just to sum up, I think

- You know, what we touched on is this really important concept of brain inflammation driving a lot of the stuff that's wrong with our society, mental health, the polarization, neurodegenerative disease.

kids issues, ADD, autism, we didn't really touch on that, but it's all linked to this neuroinflammation. And the good news is we know why and we know how to fix it. We're still learning, there's still more to know, but I think at this point we still have enough tools to actually make a difference. And so I encourage people to check out your book, "Brainwash" with your dad, David Perlmutter, check out Big Bold Health. Anything else you want to know about? - If you're interested in brain science, free newsletter, austinperlmutter.com. - austinperlmutter.com, check it out. Thanks so much, Austin.

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