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Ep. 496 We Got Brain Health All Wrong – The Shocking Link Between Inflammation, Stress & Aging with Dr. Austin Perlmutter

  • Team Cynthia
  • 5 days ago
  • 40 min read

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Today, I am thrilled to connect with Dr. Austin Perlmutter, a board-certified internal medicine physician, New York Times bestselling author, researcher, educator, podcaster, and entrepreneur. He is on a mission to help people get their brains unstuck for better mental and cognitive health. 


In our conversation today, we explore brain inflammation and its connection to longevity, the differences between acute and chronic inflammation, the influence of environmental factors, and how exposure to negative news and biases can elevate stress and affect our brain health. We examine how consumer culture promotes stress and disconnection, and we unpack the immune-metabolic effects of estrogen and its impact on neuroplasticity and our ability to learn. We also focus on the role of nutrition and nutraceuticals, and we discuss the relationship between the brain, gut, and the vagus nerve.


This discussion with Dr. Austin Perlmutter is rich and insightful, and I look forward to welcoming him back for further exploration into the science and research.


IN THIS EPISODE, YOU WILL LEARN:

  • Why brain inflammation becomes an issue for many women as they navigate middle age and beyond

  • How inflammation leads to constant changes in our cognitive and mental state

  • Various environmental factors and other inputs that could influence brain inflammation

  • Some easy ways to positively impact your brain health and cognition

  • How chronic stress affects the brain

  • How the gut microbiome and the gut immune system influence cognitive and mental health

  • The long-term health benefits of avoiding processed foods and following a Mediterranean diet 

  • The importance of being conscientious and purposeful about the quality of the foods you eat

  • Dr. Perlmutter shares easy and cost-effective ways to improve your cognitive, mental, and overall health


Bio:

Dr. Austin Perlmutter is a board-certified internal medicine physician, New York Times bestselling author, published researcher, and a leading expert on how lifestyle and environmental factors impact mental health. His mission is to help people reclaim their mental and physical health by addressing the biological basis of “stuckness” that disrupts brain function and emotional balance. He is a co-producer of the Alzheimer’s: The Science of Prevention series and the host of the Better Brain Blueprint series, where he provides actionable strategies to support brain resilience.

Dr. Perlmutter currently serves as the Managing Director at Big Bold Health, a food-as-medicine company focused on helping people rejuvenate health through better immune function, where he has published a pioneering study exploring the effects of plant nutrients on human aging through epigenetics.

“What happens in your skull is the driver of your life experience, your mental and cognitive health, and your ability to enjoy life.”


– Dr. Austin Perlmutter

Connect with Cynthia Thurlow  


Connect with Dr. Austin Perlmutter


Transcript:


Cynthia Thurlow: [00:00:03] Welcome to Everyday Wellness Podcast. I'm your host, Nurse Practitioner Cynthia Thurlow. This podcast is designed to educate, empower and inspire you to achieve your health and wellness goals. My goal and intent is to provide you with the best content and conversations from leaders in the health and wellness industry each week and impact over a million lives. 


[00:00:29] Today, I had the honor of connecting with Dr. Austin Perlmutter. He is a board-certified internal medicine physician, New York Times bestselling author, researcher, educator, podcaster and entrepreneur and his mission is to help people get their brains unstuck for better mental and cognitive health. 


[00:00:47] Today, we spoke at length about brain inflammation and longevity, drivers of neuroinflammation, acute versus chronic inflammation, as well as environmental inputs, the impact of negativity in the news and negative biases on stress levels and brain health, the consumerist cultures and how it feeds, “the machine,” the immune-metabolic effects of estrogen and its impact on neuroplasticity and our ability to learn, the role of nutrition and nutraceuticals and lastly, the bidirectional relationship between the brain and the gut as well as the vagus nerve. A truly invaluable conversation and I look forward to having Dr. Perlmutter back again to dive a little bit deeper into the science and research. 


[00:01:34] Dr. Perlmutter, I've really been looking forward to this conversation. Welcome to Everyday Wellness. 


Dr. Austin Perlmutter: [00:01:39] Thank you so much for having me. I'm excited about it as well. 


Cynthia Thurlow: [00:01:42] Yeah. Why do you think brain inflammation for many women starts to become problematic as they are navigating middle age and beyond? 


Dr. Austin Perlmutter: [00:01:50] Yeah, I think that brain inflammation is the most important thing that we should be talking about more. And the reason I'd say this is because most things that we talk about in health, they matter. So, if you have pain in your foot, it matters. If you have pain in your knee, it matters. If you have heart disease, it matters. If you have diabetes, it matters. But it all really is significant because of what it does to your cognitive and mental state, meaning what happens in your skull in that two to three pounds of mostly fat that we call the brain is the driver of our life experience, our mental health, our cognitive health, our ability to enjoy this life. 


[00:02:25] And as much as we've created this artificial separation between the brain and the body, the reality is that what happens in the body directly impacts the brain and of the systems within the body that influence the brain, the immune system and in particular brain inflammation is key to this puzzle. And so, I've been heavily invested in understanding this research, because it is critical to understanding why mental health takes such a hit at various times in our lives, why cognition drops off at various periods in our lives, but even why people tend to resort to violent behavior, why we become disconnected from other people in our lives. Brain inflammation is at the heart of the matter. So, this is something that everyone really needs to pay attention to. And it does matter more in certain periods of life, in particular midlife. 


[00:03:14] And there's research that was recently published showing that inflammation appears to be a key driver of brain longevity, meaning how long your brain is operating at a high level versus beginning that decline towards cognitive impairment. So, absolutely everybody needs to care about this tends to be a little bit more relevant in certain populations. And I think we'll talk about today why in women that may be more important specifically at a certain time in life where hormones are changing. Estrogen, for example, plays a key role in brain inflammation and neuroplasticity. But this is one of those topics where when you actually hear the science, you're going to be compelled to learn more. 


Cynthia Thurlow: [00:03:52] Yeah, I think it could not be more important and more timely. And I think back to when I first read your coauthored book with your father Brain Wash, coming out of the crux of the pandemic, when everyone was dealing with a new normal that they had never anticipated. But when I reflect on what patients are sharing with me, what they are experiencing as they are navigating a new normal. And just like puberty is when our hormones are ramping up, perimenopause for many women is when we get this decline in hormones and in some instances, 20 to 30% greater levels of circulating estradiol, which can drive a lot of the symptoms that women experience. 


[00:04:33] But certainly it's been my clinical experience, personal experience, that the latter stages of perimenopause, the beginning of menopause, is when many women will just start saying that they just don't feel like themselves. They're having trouble remembering things. They're feeling like, they're not getting the same quality of sleep. They don't navigate stress quite as effectively. They're struggling to learn new things. You know, if maybe they're taking a class or they're trying to remember medical research that they're looking at in the context of what they can share with their patients or with their clients. And so from your perspective, what are some of the silent drivers of neuroinflammation that many patients or individuals listening may not be aware of, that can be contributing to not just symptoms, but also negatively impacting long-term brain health. 


Dr. Austin Perlmutter: [00:05:26] Sure, it's such a good question. And before we get to some of the specific drivers of neuroinflammation, I just want to comment on what you mentioned, because this is such an overlooked point, which is that brain health is not a binary system. It's not as though we fall asleep one night, brain's doing great, wake up with Alzheimer's the next day. And the same can be said for mental health conditions, unless something very specific happens, you're probably not going to go to sleep feeling wonderful, having a wonderful couple of months, and then wake up the next day with major depression. And why that's so important is because we've come to understand that just like a heart attack that doesn't come out of the blue, that is a reflection of buildup in your coronary arteries over decades, that brain health exists on a continuum. 


[00:06:12] And so, some conditions-- and I bring up Alzheimer's dementia, the most common form of dementia that disproportionately affects women, some conditions develop over time. So, the precursors to Alzheimer's dementia may begin in your 20s and your 30s and really be exacerbated by immune and metabolic dysfunction in middle age. But even the things that don't necessarily cause an overt diagnostic condition, so not major depression, not Alzheimer's disease, but the ebbs and flows of cognition and mental health, these things change each day as a reflection of environmental inputs. And one of the most important of those environmental inputs is inflammation. And this is something we talked about, as you mentioned in Brain Wash, that completely changes the way I think we look at the brain, which is that each day the way we think, the way we feel is being modulated, it's being modified by immune stimuli. 


[00:07:03] And we saw this during the pandemic where so many people were experiencing depression either because they had COVID and COVID-related depression, or long COVID-related depression, now well established or because they were having an unhealthy lifestyle, because they were being kept inside, away from friends and family eating unhealthy food, generating inflammation and predisposing people to depression. So, inflammation here is a driving system that leads to moment-to-moment changes in our cognitive and mental state. And the last example I'll give here before we get into some of the drivers of inflammation is having people reflect on how they feel when they are sick. So, if you have the flu or a bad cold or you just come down with some bug, think about how your brain functions. And this maybe isn't universal. 


[00:07:52] Some people may feel completely fine, but on average, what the research shows is that when we are sick, we experience sickness behavior, meaning we start to feel socially isolated, we start to feel depressed, we start to feel brain fog. These are the direct outputs of inflammation from the body getting into the brain and changing how we think, how we act and how we feel. We know, for example, that inflammation in the bloodstream leads to fever when those signals get to the brain, but it also leads to changes in our cognitive and mental state. So, really really important framework to understand. Now, getting back to what you had asked about what's actually driving this inflammation, I think it's important to understand first the scope of brain conditions associated with neuroinflammation, brain inflammation. 


[00:08:38] So, I mentioned Alzheimer's disease, but a host of neurodegenerative disease, so Parkinson's, multiple sclerosis, ALS. Mental health wise, we have depression, schizophrenia, bipolar, ADHD, PTSD. And that's just the tip of the iceberg. Beyond this, we're also understanding that inflammation in the brain is tethered to impulsive decision making, is tethered to, as I mentioned, violent crime, is tethered to alterations in IQ, is alterations in our behavior. So, this really is a governing force that is dictating how we interact with the world. So, then the question is, what is actually driving that inflammation? If inflammation is such a big deal, and it is, what is actually creating this problem? And like most things, there are many variables that synergistically interface to generate what we would call pathology or problems with inflammation. 


[00:09:29] So, I like to think about these as basically environmental inputs. And so, you can get an environmental input from multiple places in your physiology. So, it can be chemicals on your skin, it can be the food that you eat, it can be the air that you inhale, but it can also be the data that you consume through your eyes and your ears, meaning watching stressful news or listening to stressful news. These are direct signals into the brain that can ramp up inflammation. One aggregating theme that is helpful, I think here is to think about inflammation as really the body's response to a perceived threat, a danger signal, and something that I'm sure your listeners are well aware of is inflammation is not necessarily by definition a problem. It is a good thing. It is our body's ability to fend off threats. 


[00:10:17] But when it becomes chronic, when it becomes something that we don't necessarily overcome. That's where it starts to degrade our system and our brains. So, in the short run, inflammation is an amazing way for us to get rid of something that can create problems. In the long run, it just becomes like a degradation, this caustic acid that eats away at our brain health. So, going back to some of those things that are influencing brain inflammation, a quick list. So, smoke, which includes smoking or air pollution, certain pharmaceuticals, are going to influence brain immunity for the better and for the worse. Substance use, so alcohol, especially at high levels, has been shown to be a potent neuroinflammatory stimuli. We also know that we have certain heavy metals that are linked to neuroinflammation.


[00:11:04] We know that traumatic brain injury or traumatic head injury is a stimulus for brain inflammation. Infectious agents, so COVID is one. But multiple other bacteria and other pathogens can influence brain inflammation. Where I think, many people are going to find value, though, is going away from some of those untoward things like diabetes and chronic metabolic dysfunction. Basically, any form of chronic metabolic dysfunction predisposes a person to neuroinflammation. We can talk about some of those pathways. So different dietary aspects, dysbiosis, gut changes influence brain inflammation, the aging process itself, stress, psychological or physical stress. On the flipside, we're learning that certain molecules like psychedelics and even SSRI help to decrease brain inflammation. 


[00:11:50] So that isn't an exhaustive list, But I guess just to give listeners a little bit of context, you have all these different stimuli, these environmental inputs that can influence the brain's immune system. Why that's great is because each of these can provide an opportunity for us to fine tune brain inflammation, and by doing so, directly act on cognition and mood and also behavior. 


Cynthia Thurlow: [00:12:13] And obviously, some of these things we have some control over. We may not be able to leave a part of the country or part of the world where we're exposed to, whether we're in a city and maybe the air quality is not as good as it might be in a more rural area. But a lot of the choices that we make day to day have a direct impact on brain health and inflammation. And from your perspective, what do you think are some of the more accessible things that everyone can do to positively impact brain health and cognition, starting at kind of a lower level before we move up to more intense things? 


Dr. Austin Perlmutter: [00:12:51] Yeah, for sure. And I think to your point, there's a lot we can do. And these don't have to be expensive things. They're not really premium products. What we're talking about sometimes is just decreasing your exposure to stuff that you don't need. So, let's go over a basic one, TBI, traumatic brain injury. So, this is a potent and long-term signal for brain inflammation. What can you do? Well, the basic things are wearing a seatbelt and wearing a helmet. If you are somebody with balance issues, or if you know people, parents, family members or friends with balance issues, basically creating scenarios where you're less likely to fall. This sounds so basic, and it is, and yet it is so important. 


[00:13:32] Not only do falls predispose people to disability, not only do hip fractures create an incredibly increased mortality in the elderly, but falls, and specifically falls where you bump your head are neuroinflammatory stimuli. If we're going to talk about, I guess, some of the more high-yield things for people who maybe aren't so concerned about TBI. So, I do think when we think about inputs, you think about what comes through your gut and gets to your brain. You think about what comes through your lungs and gets to your brain. We can talk about what comes through our muscles to get to our brains. That's a really exciting one. Learning about Myokines, I know this is a domain that you've been talking about for a while, but also the sensory data. So, what can we do to decrease the neuroinflammatory or brain inflammatory stimuli? 


[00:14:18] Let's go there just for a moment because I think that's really about the most cost effective of anything you can do. So, the average person in the United States is spending 11 plus hours of their day interacting with media. And that means roughly four hours watching TV, a little over two hours on their phones, a lot of time listening to the radio. And then everything else fills in the additional hours. Now, I'm not opposed to people engaging with the media. I think it is important to become informed. But what we see is based on data from the American Psychological Association, that at the top of the list of things that create stress in Americans is exposure to the news. So, there's a really important question that we need to ask ourselves. Are we becoming informed? Are we just becoming upset? 


[00:15:02] Because while we can say, “Well, watching this or doing this stressed me out, maybe it led to a little bit of worse sleep.” What we don't necessarily appreciate is that chronic stress, which comes from news exposure, is a direct driver of brain inflammation. So, in the acute phase, stress actually helps to suppress inflammation. But over time, that system becomes all wonky. And so, you actually upregulate inflammatory molecules. So very easy hack for people here is to ask themselves as they're engaging with the media, “Am I becoming informed or am I just becoming upset?” And a great signal to know the difference is “Am I seeing the same content or hearing the same content multiple times? Am I doing anything with this information I'm learning.” 


[00:15:47] So, do every day I just sit down after I get home from work and listen to two hours of these TV hosts telling me about how terrible the world is. And I don't do anything except for just spread that negativity to my friends and family. That is a good example of a neuroinflammatory driver that we can significantly mitigate. So that's what we consume through our eyes and our ears. And I think we'll get into the food piece because obviously that's really interesting in terms of what foods influence the gut microbiome in which way is to promote pathways of gut brain inflammatory response or the opposite. 


[00:16:23] But again, in this age of everything being these really expensive health biohacking interventions, I think it's so important to understand that you have agency over these incredibly cheap ways to decrease inflammation by simply doing less of the things that other people do. 


Cynthia Thurlow: [00:16:40] Yeah, it's so interesting because again, I go back to the pandemic, but I definitely felt that it was probably the first time in my adult life that I had to start tuning out a lot of the news because it was, to your point, incredibly negative, fear mongering, to a point of which-- and I'm a parent and I'll be the first person to say, I like to be informed, but when I get to a point where the toxic bucket has been overflowing and overfilled, it's not healthy for my mental health. But I also think a lot of individuals, and I won't call them out specifically, but I have some family members that during the pandemic they just sat in front of the TV and were so fearful of all the information being spread, they didn't even want to leave their homes. 


[00:17:23] And we know the net impact of loneliness and lack of social connection and the impact on our mental health. And so, I think for everyone listening, deciding for ourselves as adults, how do you choose to engage with the media? How do you choose to engage with, whether it's a streaming service, whether it is entertainment, and understanding that complex interrelationship that if you trigger your fear center in your brain, your amygdala, that in many instances can override our thinking part of our brain and that in and of itself can lead to poor decision making and I think for the vast majority of our listeners, these are really smart, well-informed individuals who are just trying to ensure that they're making good decisions for themselves, both physically, emotionally, and spiritually. 


Dr. Austin Perlmutter: [00:18:13] Yeah, I'd like to comment on that just for a moment, because I think it is a reality now that if we go along with the flow in terms of consuming the content, the food, the interactions that are most standardized, that we will find ourselves incredibly unhealthy and incredibly unwell. And there are a number of reasons why that's the case. But if you just look at base rates of health in the United States, what you see is that the average person is now taking one or more medications, has at least one chronic disease about 40% of people have two or more. And this isn't to say blaming people for those types of outcomes. What it is to say is that if you do what most people do, you will statistically speaking, find yourself unhealthy. 


[00:18:55] And the reason is because we've set up a system that is not optimized for cognitive or mental health. I think that's really important for people to hear. I know that we care about the GDP, I know that we care about America being a super strong country, but those don't necessarily equate to better cognitive and mental health. And in many ways, they're exactly opposite from the things that we know optimize towards those outcomes. There's a reason why the United States keeps falling behind when it comes to our mental health outcomes. It's not as though the more money we have we become happier, we become healthier. 


[00:19:28] So, I think that as we look at what we actually do in a given day and the content that we consume, we recognize that there are these incentive structures that are out of alignment with our mental health. And I think the news is a great example because we know that there is this progressive negativity bias in the news, meaning we know that people who are in charge of producing news stories appreciate that, as you said, we have this fear center in our brains called the amygdala. It does other things, but it is incredibly sensitive to perceived threats. And so, if you were to put up a happy story versus a story about a bunch of people in your neighborhood that were going around and doing bad things, your brain will always pay attention to that second story. 


[00:20:10] So, the issue here is that it may not be people in your neighborhood, it may be people somewhere across the world, and it may not be that they've done something terrible, but the news is really highlighting the possibility that they could do something terrible. And because of our negativity bias, we can't turn off that TV. So now we wind up carrying around this idea that we're perpetually in danger, which increases stress hormones, which ramps up neuroinflammation, which leads us to a higher risk for developing depression, which leads us to a higher risk of experiencing chronic psychological stress. We know that inflammation tethers to loneliness as well as to just general isolation. So, now we're biasing behavior and thought patterns towards these negative outcomes. And I don't think news stations are necessarily trying to do any of this. 


[00:20:57] They're just trying to keep our eyes on the screen. And I'd extent this too, because it's not all about the TV, it's not all about the radio. If you go on social media, there are different forms of stress and it's not just the world is ending, but it's, “Oh, look at my friend from high school who now has a yacht and who seems to spend every three days in Ibiza, because somehow, they're super financially well off and is in better shape than I am and their kids are healthier than my kids.” And so, there's this other stress, which is social comparison, which we know drives social media. There's no aspect of social media which is really authentic. It is snapshots of what people want to display. So, they're always putting the best stuff on display. 


[00:21:37] So, we wind up existing in this society in which we are perpetually being fed this distorted information that biases our brains towards a state of inflammation and that then leads to worse mental health, worse cognitive health, more isolation from each other. And the last thing I'll say on this, just getting back to the GDP, this state of feeling really bad about ourselves and bad about, the state of the world is a great scenario for us to be sucked into buying junk that we don't need. Consumerist culture, which is, I feel really bad right now. Instead of doing something to decrease the amount of badness in the future, I'm going to buy something that I don't need. So, I can forget about it for the moment or I'm just going to scroll on social media for an hour so I can numb out to all these bad feelings I'm having.


[00:22:25] So, it traps us in this scenario in which we are perpetually feeding this machine. And I know there's a lot of conversation right now about what can we do in America to become healthier, to have better longevity. I think that's all wonderful, but we have to look at these incentive structures and until they're actually aligned with human health outcomes like longevity, mental health, cognitive health, I think we need to be still very cautious of just embracing the idea that more of the things that we're already doing is going to create the solution. 


Cynthia Thurlow: [00:22:56] Well, that is such a powerful vignette of concepts and I want listeners to really be thinking about this that, unfortunately we're in a time where if it bleeds, it leads. That's what my writing friends would tell me. That you know, whether it's TV or news articles, anything that is provocative, negative, it is designed so that we are much more interested in learning about it, which is why if I'm on social media, I jokingly tell people I watch like funny animal videos because they make me happy. And that's the stuff that I consume. If I'm taking a couple minutes in between doing something and I just want to be entertained, that's probably not most people. 


[00:23:37] With that being said, what is going on physiologically in our bodies when we are under the threat of stress, whether it's perceived or actual stress? And why is chronic stress so detrimental not only to brain health, but overall physical health? 


Dr. Austin Perlmutter: [00:23:53] Yeah, it's such an interesting thing if you take a step back and say, “What if the body was always doing the right thing and we’re just feeding it the wrong signals?” And I think chronic stress is the perfect example of that. So, these cavemen ancestors of ours always get a lot of play with the saber-toothed cat. So, we'll try to create a different analogy. But just thinking about how our brains are wired, they're wired to keep us alive. They're not designed. They're not wired for us to be happy. They're not designed for us to experience life satisfaction. That's not the goal of the brain. The goal of the brain is to keep us alive and to some extent to have us procreate. 


[00:24:31] So, if we think about how that has played out over time, historically, if we were in danger, that danger would usually be a short-lived threat. So, maybe there was that saber-toothed cat that got into the cave and we had to deal with it, otherwise it was going to eat us. But once it was gone, we were able to go back to whatever semblance of a standard life we had. The difference is that now we have these perpetual stressors. I'm worried about my 401(k). I'm worried about the potential for an international war to break out. I'm worried about the fact that at my job my coworkers seem not to really like me and I'm concerned about whether I'm unlikable. All these things that sit in our brains and we ruminate over them. 


[00:25:13] If we think about what happens in the brain with a psychological stress, there's this tunnel vision effect that people have described. And I think it's a really helpful framing for this. So, if you were walking down the street and all of a sudden velociraptor, right? Come around a corner, you would forget about your taxes, you'd forget about your coworker, you'd forget about your 401k, and you'd be completely focused on this velociraptor, right? You'd have to decide, do I fight the velociraptor, do I run away or do I freeze? These are the standard options, all of which make a lot of sense, okay. Now practically speaking, you're going to recognize that it's somebody in a costume and then you'll say, “Okay, well clearly, I don't have to fight this velociraptor. We're not in Jurassic Park. This isn't reality.” 


[00:25:59] And so your sympathetic nervous system will calm down, you'll stop releasing so much cortisol, your heart rate will come down and you'll be able to go about your day-to-day life. But in the moment, it made total sense that your brain was focused on this threat in front of you and you blocked out everything else at the expense of worrying about tomorrow. You were focused on this thing today. But if we consider what happens when that plays out over time, meaning you have these chronic nagging stresses in the back of your brain. There's a couple of pathways that this activates. There are two major ones, one being the HPA axis, which I know your listeners are quite familiar with. The other one being the sympathetic nervous system activation. 


[00:26:36] So, molecules like epinephrine and norepinephrine get revved up, heart rate goes up, blood pressure goes up. And again, these things make total sense in the short run because you want to increase glucose. So, you want to increase bioavailable energy to fight off that velociraptor or threat. You want to increase heart rate and sympathetic nervous system tone so that you have the cardiovascular reserve to escape or fight. But long term, when those systems stay on what seems to happen is you wear down the body's ability to adapt to it. And there are multiple changes that seem to happen within the brain, both in terms of sensitivity at the what's called glucocorticoid receptor. 


[00:27:17] The focus, though, that we're most interested in the writing of the book Brain Wash is that chronic stress seems to degrade the connection between a part of the brain called the prefrontal cortex and the limbic system, specifically the amygdala. Why that matters so much is because in order for us to be able to process the world not from a reactive state, but from a reflective state, we need to be able to engage in what is called top-down control. Top-down control means that if you hear a bump in your bedroom in the night, you may instantly think, “Okay, maybe somebody's breaking in.” But then you have the ability to say, no, I've heard this bump before. It's just the wind. I'm able to go back to sleep. When you lose that ability, you become more reactive. 


[00:28:02] And when you lose that ability, there's also correlations with worse mental health, worse decision making. So, chronic stress in particular appears to amplify the power of the amygdala and decrease the power of the prefrontal cortex. There's actually data, primarily animal based, showing atrophy of the prefrontal cortex in the context of chronic stress. And a fringe effect of what seems to happen in the context of chronic stress is that it revs up inflammation. That actually makes sense because you've gone from a scenario in which we want to suppress inflammation because that's actually what stress hormones do in the short run, to saying, “Hey, like this threat hasn't gone away. We actually need the body to mount a threat response.” And that threat response is an increase inflammation. 


[00:28:46] We're not talking here about incredibly high levels of inflammation as the result of chronic stress to use, for example, CRP levels. So, CRP maybe goes up to 50 or even higher in the context of an acute infection. What we're talking about here is maybe 2, 3, 5, 10, right? So, these are levels that are much lower, but over time, they basically degrade our neuronal circuitry. High levels of inflammation and high levels of clinical chronic stress are two of the most potent drivers of Alzheimer's disease, of mental health conditions, in terms of how they interface in this what's called immune-metabolic context, the immune system and our metabolism coming together. So, you in essence create a scenario where your body and your brain is perpetually experiencing a danger signal. 


[00:29:37] And to go back to where we started this conversation, it's easy to blame the body or the brain and say, “You're really messing up.” But I think instead you say, “The brain and the body are doing what they can with the data they have available, and they are trying to keep you alive, and they are perceiving a danger signal out there.” Again, because you're worried about your job, because you're worried about your relationships, because you're worried about the fate of the planet and the possibility of these global wars spiraling out of control. And it, in essence, programs your brain and your body to a state of worse mental and cognitive health. 


[00:30:09] So, in order for us to not have that happen, we have to break that loop somehow, and we have to be taking in different signals, and we need to be engaging in practices that allow us to interpret the signals we are bringing in a different way. So, it's kind of like you're not just taking direct input from the TV, but rather maybe you do it in smaller doses or maybe you offset it a little bit with some meditation, some mindfulness, so that you're not allowing those thoughts or those ideas to directly get embedded in your brain and become part of your identity. 


[00:30:41] But the bottom line here is, in order to protect our brains, we need to create a block in this constant stream of negativity and stress that if we don't, we'll be perpetually flowing in through our eyes, through our ears, through our diets even, through our lungs, and we'll program our brains to worse health outcomes. 


Cynthia Thurlow: [00:31:02] So, if someone's listening and they're curious about how well they're navigating? Managing acute versus chronic stress, what are some ways that the body will let them know? What are some of the most common symptoms that your patients report or your research that you've done in these areas have reported that are most commonly seen or reported from patients. 


Dr. Austin Perlmutter: [00:31:26] There are a lot of ways that stress can manifest. As your listeners know well, different people experience different outcomes if you have chronically dysregulated HPA function. One of the biggest signals, I would say, is the sleep. And so, there are a number of reasons why a person may not be sleeping. It could be obstructive sleep apnea. It could be restless leg syndrome. It could be the temperature in the bedroom. But if you find yourself waking up with racing thoughts or not able to sleep because of racing thoughts, that is an amazing signal. I want to get back to what I said before, which is your brain's just tasked with keeping you alive. And so, stress is-- what it's designed to do is to get you to focus on some unresolved issue. That is what stress is. It's an unresolved issue. 


[00:32:05] So, if you get in bed and your brain says, hey, we still need to worry about this thing, then your body will say, “Okay, well, I guess it's not safe to sleep.” We need to handle this first. So, if you find yourself laying in bed, racing thoughts, experiencing those types of anxieties that wake you up, get you out of bed early in the morning, where you're feeling your heart racing, that is an amazing signal that there is some stress in your body. Now, it doesn't mean for sure that's the issue. You could have a pheochromocytoma or some random thing, right? That is highly unlikely. 


[00:32:37] But the point here being that if you're having trouble with sleep, especially if you find yourself experiencing these anxious thoughts, that is when your brain finally has the opportunity to give you a space so that you can see what's happening. Often during the day, we're so unaware of what's happening, we just kind of covered it up. So, I'm experiencing anxiety, but I'm going to go on social media for a little while, or I'm feeling sleepy because I was super stressed last night, but I'm just going to get that giant coffee and cover up for it for a moment. 


[00:33:04] But when you get in bed and you have that little moment where you're actually getting to see how your thoughts move. The other way would be if people practice mindfulness or meditation and they just close their eyes and see how their thoughts are processed in a given moment. I think that's a great signal. Now, there are so many other ways that this can manifest. Brain fog or people experiencing cognitive issues, people obviously experiencing psychological issues, people experiencing relationship issues, stress can manifest in many different ways. I find that one of the ways that you often see this happening is when people feel like they're having more trouble focusing. So, certainly sometimes that can be a signal of something more significant happening. But oftentimes, people say, “Oh, you know, I'm forgetting this, that, or the other.” 


[00:33:49] It doesn't necessarily mean that you have MCI or developing dementia. Sometimes, it is just your brain is overloaded. We know that higher levels of cortisol can impair people making rational and thoughtful decisions, especially when they're trying to multitask. So, all ways to look at this, but I really would go back to sleep. And when your head hits the pillow, what happens? Or do you find yourself waking up in the middle of the night with your thoughts racing? It's another good signal. 


Cynthia Thurlow: [00:34:13] Yeah, I think it's so important because sleep really is foundational to our health. And I think for many women at this stage of life, it may be the first time that they're experiencing an inability to fall asleep or stay asleep. And I think we're so distracted throughout our daily lives that until we are like in that sleep mode, it may be the first time that we're realizing, “Oh, there's been this nagging feeling or suspicion all day long or the last week that I'm finally having to deal with because my mind is quieter.” One thing that I think is helpful to understand is that there's this complex interrelationship, this bidirectional relationship between our guts and our brains. 


[00:34:52] And I think for a lot of individuals, helping them understand that if they get, a nervous stomach or they say they just feel like they're not digesting their food well, then in many instances it can be a sign that they're dealing with chronic stress or they're nauseous, can be a direct reflection of this chronic unrelenting stress that I think for many of us, we tend to downplay, to be quite honest. Where we take on the concerns of the world, we're caretakers and all of a sudden the last person that we're oftentimes taking care of is ourselves. 


Dr. Austin Perlmutter: [00:35:23] Mm-hmm. Agreed. Well, let's talk a little bit about that. So, this gut-brain connection and how stress factors in. It's funny, we tend to experience stress as a psychological stress and we say, “Oh, well, I am stressed or I am anxious.” But that's actually just the downstream effect of these other systems in the body. And the gut is a great example of that. So, we would say, “Well, my brain is experiencing stress.” But we may not ask, well, why is my brain experiencing stress? Unless we can tether it to, “Oh, well, somebody just cut me off in traffic and that's the reason for it.” But stress is really an outcome of a complex state of things within your brain changing. 


[00:35:59] And so many of those inputs, as you said, relate to the superhighway between your gut and your brain as we've started to understand the role of the microbiome. So, not just the actual makeup of the microbes, but the things that they produce that get into our bloodstream that influence our metabolism and our immune system, as well as how various signals from within the gut can be transduced through the enteric nervous system, through the vagus nerve, and therefore reaching the brain. How other molecules, for the better and for the worse, can get into our bloodstream and influence the blood brain barrier and the brain. 


[00:36:33] We just recognize that at the level where we experience how our brains are functioning, so much has already happened and so much data has already been kind of interpreted by our neurons and our glial cells to lead to that outcome. I really like, as you do, this gut-brain connection because of how fascinating the research is and because of how actionable it is. Because we, every day, unless we're doing a long fast, don't get to opt out of eating something, doing something. And even beyond food, we know sleep and exercise and all these other lifestyle activities influence the state of our gut. Where it gets interesting for me is in particular, the role of the gut microbiome and this interface between the gut microbiome and the gut immune system on our cognitive and mental state.


[00:37:19] Now, you would think that what happens in the gut stays in the gut. And in some ways that is true because it's not as though all the serotonin in our gut actually gets to the brain, but precursor molecules like tryptophan, which does come to some extent from gut microbes and is obviously coming from our diet, does need to get to the brain, where it can be then converted into one of two different pathways ways, one of which produces serotonin, the other one produces potentially neurotoxic and neuroinflammatory molecules like quinolinic acid. So, what happens in the gut, obviously vital to what happens in the brain. And we're now understanding that the various states of the gut microbiome, the makeup of the microbes influences mental health state. We're also understanding that people with dementia, for example, have different compositions of the gut microbiome. 


[00:38:04] And it may not just be that the microbe setup is the important thing, but rather the molecules produced by the gut microbes and the interface between the gut microbiome and the gut immune system may be equally or even more important. So, it's transforming again, this concept of the gut or of the brain and the body being separate to something much bigger. And we're getting a lot of data from animal studies and now a lot more data from human studies. But this is why, really, food is so transformational, I think for brain health. 


[00:38:35] Not only does it become the building blocks of the brain, influence brain immunity through things like omega-3s, which we have to consume in our diet because we don't produce enough of the EPA and DHA on our own, but that the food that we eat programs the gut microbiome, changes the gut immune system, speaks to the vagus nerves, speaks to the bloodstream, influences molecules like lipopolysaccharides that we know are potent brain inflammatory stimuli. And by doing so, we know that every single meal that we eat can be a vote for better or for worse brain health. So, this isn't necessarily to go down the route of saying every meal has to be perfectly organic, locally sourced, and ideal, but it is saying that every meal is a potential to vote for or against good brain health.


[00:39:23] And the last thing I'll say on this is, there's a lot going on with specific nutrients that come from our food that can be influenced by the microbiome. When we think about how to nurture a healthy microbiome, historically we've thought about fiber, and most Americans get around half of the daily recommendation for fiber. That matters because fiber correlates with inflammation, in that higher levels of fiber intake is correlated with lower levels of CRP, higher levels of fiber corelates with lower levels of dementia, higher levels of fiber correlates with longer lifespan. So, you want more fiber. But we also appreciate that the thousands of molecules found in our food, which we've historically thought of as just throwaway molecules like polyphenols, actually impact the gut microbiome and the gut immune system. 


[00:40:09] So, this is so much bigger than just saying, well, get enough calories, get enough fats, carbs and proteins. It's actually talking about how we can influence the makeup of the gut microbiome, the gut immune system, and even impact gut cells that produce molecules like GLP-1 through a comprehensive food. Not just the nutrient in a food, but the actual food itself that contains this spectrum of molecules, some of which we're only just beginning to scratch the surface of what they do when we ingest them. And again, it's not just about making sure you're getting your macros right. It's about eating real food that contains all of this additional data. 


Cynthia Thurlow: [00:40:47] Well, and I think it's so important, when we speak to nutrition, which I think in many ways in the health and wellness industry, it's gotten very polarizing. You know, this is right or wrong. Carnivore is right for one person. Vegan is right for someone else. Ketogenic diets are the fad of the moment. And I'm just thinking of some things that a lot of people are speaking to, but I think it's so much more nuanced than that. And I love that you brought up these signaling molecules, polyphenols, postbiotics, things like urolithin A. All of these contributors to a healthy gut microbiome and then ultimately also contributing to a healthy brain health. 


[00:41:25] For you-- are there non-negotiables for you personally in terms of foods that you regularly consume because there are health benefits, but also because they make you feel good physically and also mentally?


Dr. Austin Perlmutter: [00:41:38] Sure. So, I guess I do two things. One is I try to avoid almost always processed food in any way, shape that it may exist. That means anything with added sugar. With that aside, I mean, it's not a universal thing. Obviously, there's times where you can't get away from it. But if we're going to say no processed food most days, then what am I actually bringing in? And so, I consume as much as I can, a Mediterranean pattern diet. Now, I want to just go back to something you said, which is we live in an age where if you go online and ask two health experts for the best diet, they're going to give you five answers. So, meaning you're always going to hear more complexity and more diets than you know what to do with. 


[00:42:21] And I find this to be a real challenge. Because as much as I agree there are certain people for whom certain diets are optimal, I think if you're just going on social media and you're trying to figure out what can I do to just generally get a little bit healthier, you're going to be so confused. Should you be doing South Beach, Atkins, Keto, Mediterranean? In many ways, vegan and carnivore being a good example, are mutually exclusive. So, I would say if you're somebody out there who hasn't started any of this, I'd say just eating less processed food is an amazing first place to start. And I think anybody who pushes back against that, I'd love to know why. 


[00:42:58] Because it's just like, I'm sure there are people with various mutations that really need X, Y or Z, but the general population, the data is super clear. Benefits from eating more minimally processed foods. Now I said I eat primarily a Mediterranean pattern diet. And the reason for that is when you look at long-term benefits to brain health. There is no diet that has been better studied for multiple brain health outcomes. So, that's Alzheimer's disease, that's depression, and by the way, it's also an amazing diet for cardiac prevention or heart disease prevention and a host of other diseases including metabolic dysfunction like diabetes. What that actually looks like is prioritizing the consumption of minimally processed foods, which is plant foods, which is animal proteins as well. 


[00:43:44] I'm not a vegan, have started to deprioritize animal-based protein relative to eating fish and more poultry. Talk a little bit about that. Some of that comes from just basically getting my own lab data and understanding the effect of saturated fats on my lipid panel. I'm sure there's lots of people or there are lots of people with lots of opinions about LDL and particle size. I don't necessarily want to get into all that, but what I would say is it is our diet, we include lots of healthy fat, so lots of olive oil. We also do lots of fiber and plant-based foods. We do lots of fish, more seafood, lots of nuts, lots of seeds, lots of spices. Spices are actually the most concentrated source of polyphenols. 


[00:44:26] They're not the top source of polyphenols in the American diet because that would be coffee, which I'm also a [Cynthia laughs] fan of, dark chocolate, we tend not to do much with sugar in general. And then tea, which has been historically studied to be a very rich source of polyphenols. We have lots of different teas, lots of fresh vegetables and nothing that I'm saying here is going to be all that controversial or exciting to people. We don't do refined carbohydrates in any way, shape or form. I think that we could talk a little bit about that. But this is the diet that myself and my wife feel is most optimized towards our specific needs, which is trying to plan for brain health tomorrow in terms of protecting our mental and cognitive health but also preventing long-term cognitive decline. 


[00:45:12] And I do think, you mentioned the keto diet. I think that there is something important to be said for people with preexisting metabolic disease or metabolic disorders which depending on the study you look at is between 88 to 92% of the American population with some aspect of metabolic dysfunction. So, a lower carbohydrate diet I think can be especially helpful for those populations to reset insulin sensitivity, to reset people towards a healthier metabolic state. And long term, there's very little data on low-carb diets in terms of brain health outcomes. So, while that data is being developed, I still think we index towards the best data we have for the most people, which is more of a Mediterranean pattern diet. 


[00:45:56] So there's a lot of stuff I could talk about in terms of my specifics. So, what I do on a day where I'm exercising a lot in terms of carbohydrate content, but I think broad strokes, Mediterranean diet, we could talk a little bit about specific nutrient supplementation. I am a fan of some of these omega 3s, creatine, magnesium, but I do think again, trying to just lock in as much as you can, a diet that is minimally processed is going to be your best bet for overall and brain health.


Cynthia Thurlow: [00:46:20] Yeah, thank you so much. And I think on a lot of different levels, it's really the bio-individuality piece. I think, for so many of us-- I just had some testing done through my integrative practitioner and I had said to him, “I'm someone that has never tolerated a lot of saturated fat, so I've always leaned towards leaner cuts of meat, poultry, fish, etc., and it turns out I am a hyper absorber.” And so, it explains why if I were to eat a ribeye as an example, I wouldn't feel well, I would be nauseous. I have a very healthy gallbladder. That's always the first thing people will say is maybe it's a gallbladder issue. No, it is not. 


[00:46:56] I'm very metabolically healthy, but I found out the power of the N of 1 and 1 out of 2 of my children is the same way. And so, when we all have meals together, my husband and my younger son will have a fattier cut of meat and my older son and I will have a leaner cut of meat. And that's what makes our bodies feel good. And to your point, it's figuring out what feels good. I do better with monounsaturated fats. That's me personally. But of course, being conscientious and purposeful about the quality of the foods that we're consuming, being conscientious about limiting processed foods consistently, irrespective of who I interview and speak to, that is a consistent message. 


[00:47:36] And for everyone that's listening, maybe that's not realistic 50% of the time, but working towards consuming less processed foods, what are the things you can do day to day that are sustainable and are not breaking your budget? Because I think the other piece is when someone hears, eat less processed foods in many ways they're like, “Oh, wait a minute, that means it's more expensive.” And that hasn't been the case. You can purchase higher quality foods that are less processed and do it in a way that still honors your budget but also doesn't undermine your long-term sanity.


Dr. Austin Perlmutter: [00:48:11] 100%. I think this is so important to say because we exist in the space in which, many people, the default thing is to say all organic, regeneratively sourced, only grassfed beef and all these other things, which, sure, it's nice. And it's also not accessible for the majority of the American population right now. And right now, 2025, we still have about a third of Americans eating fast food each day. And so, remembering that's the case, it's that there's so much of an opportunity here to boost the health of so many people, millions and millions of people, by making slight changes. 


[00:48:45] And yeah, if you're on the opposite end of the spectrum and you're a biohacker and you're saying, “Well, I really want to gauge what the MCT does to my VLDL and I want to use these special SNPs to see what it's going to do to my genetic outcomes, fine. But I think it's super important to understand that if your goal is to help to create a healthier America, that population level changes are not necessarily going to reflect what is best for each individual. I would love it if every person was able to test their full nutrition panel. That's not cost effective for everybody right now. And beyond that, there is the liability to getting the labs and not having follow up with a practitioner who can tell you what to do about it. 


[00:49:27] There is a real thing that is happening right now where many people are getting this data and then they don't know what to do with it and it's just creating more concern. I think we could talk about a number of different companies that have provided some pretty amazing data, but without the backend, I think that can be even in some cases a bigger liability than not knowing at all. So, I think that there are so many ways to do this just a little bit better. We also exist in a time in which it's easy to single out specific nutrients or antinutrients and call those the boogeyman. So, we could talk about lectins, we could talk about concern with kale. 


[00:50:01] And one of the most cost-effective ways to do this is just to pressure cook a bunch of black beans, right? Like this is something we do quite often. We could say certain people don't tolerate legumes. We could say that there's antinutrients. But it's really hard to hold both of these things, which is to say that my goal is to have as many Americans and people around the world healthy as possible. And to say that eating apples is bad because a little bit of fructose is going to create metabolic syndrome. Understanding that again, most people are eating junk food most of the time, how can you be opposed to a person eating an apple? So, I'm trying to take the perspective of saying, “What is the maximum value added for the most people possible?”


[00:50:42] Which is why almost everything I do in terms of talking about brain health is just towards improving sleep, improving exercise, improving diet, improving mindfulness, improving people's general framework around how they approach the day, as opposed to saying the goal is to take this many milligrams of this or to buy this type of redlight center that's going to enhance your cognition by this percent and this study that was done in 15 people, and we need to do that research too. So, I think it's holding both. And I do different conversations depending on the audience. But understanding that your audience, maybe many women who are out there looking for those solutions to improve energy, to improve cognitive, to improve mental health. 


[00:51:24] You know, sometimes it is an incredibly esoteric thing and sometimes you do need to do thousands of dollars of labs and need to have a very targeted nutrition plan. But we shouldn't jump to that. Instead of looking for set sleep and exercise and basic nutrition and the stress and the content that we're consuming, there's not a lot of incentives for people to be promoting this type of stuff because it doesn't come with a backend. However, it is still the most studied and the most effective way to improve health at scale. So, all that is to say, all of these things matter. 


[00:51:54] But if you're not paying attention to your sleep, if you're not doing a bit of weight training to improve the production of myokines, which boost the brain, if you're not taking the basic first steps to eat a less processed diet, if you're not cutting back on your news exposure, those are amazing things that every person can do that have been studied time and time again to have significant and lasting benefits. They're just not popular to talk about on social media. 


Cynthia Thurlow: [00:52:21] Yeah, no, I 100% agree with you. And I think if we're looking to impact as many lives as possible, it has to be actionable. As much as I love gadgets, I'll be the first person to say I love gadgets. But if we're not thinking about the basics, then we don't even need to be worrying about redlight therapy, the Oura Ring, the WHOOP band, or whatever it is. I'm sorry, didn’t meant to be calling anyone out, but just the point being looking at the low-lying fruit, the things that most people can do or make an effort to work towards, that'll have a larger net impact than any of the other things that I just mentioned. 


Dr. Austin Perlmutter: [00:52:58] Totally. And also, I'll say I'm also in favor of these things as well. You know, I love using CGM, think the Oura is amazing, love the sauna, they're great things. Don't get me wrong. I just think it's also ideally, you take that first step, it's like saying, okay, well, I've never run before, but by tomorrow I want to be running a marathon. What will inevitably happen is you'll injure yourself and then you'll go back to a worse place than you were before. So, it's the walk before you run. And I think building that foundation is such a perfect place to then get you to the level at which you're benefiting from those other things. Because most of the things that we're talking about, we talking about an incremental value, a couple percentage points versus dialing in your sleep, 10, 20% better. Dialing in your diet, 10, 20% better.


[00:53:40] So, I think that it's starting there and then ideally working with somebody like you or somebody who understands how to layer in those additional interventions so that you don't find yourself saying, “Well, I eat fast food three times a day.” However, I have an Oura, so therefore I'm doing well, right, because I'm a biohacker now. It's like, that's not exactly how it works. Or I guess you can define it however you want, but you're not getting the most bang for your buck. 


Cynthia Thurlow: [00:54:06] Absolutely. This has truly been an invaluable conversation. Please let listeners know how to connect with you outside of the podcast, how to get access to your amazing work and connect with you. 


Dr. Austin Perlmutter: [00:54:17] Appreciate it. So, you can find me on austinperlmutter.com or @dr.austinperlmutter on social media. I'm doing right now couple of different projects. So, we're actually doing research on polyphenols for a company called Big Bold Health, which was started by Dr. Jeffrey Bland. And so, we published last year our first study looking at the polyphenols on Himalayan Tartary Buckwheat and their impact on longevity related pathways in Frontiers in Nutrition. For those people who like to nerd out a little bit on some of these pathways around immunometabolism, you can find that on bigboldhealth.com. You can also find @bigboldhealth on social media I do a lot of content with them, educational content. 


[00:54:58] Otherwise if you go to conferences, you can find me speaking depending on when you listen to this, A4M, a couple of A4M conferences coming up as well as some other places around the United States and a couple internationally. If you're interested in brain health, you can check out on my website and see where I'm going to be speaking next. 


Cynthia Thurlow: [00:55:13] Awesome. Thank you again for your time today.


Dr. Austin Perlmutter: [00:55:15] For sure.


Cynthia Thurlow: [00:55:17] If you love this podcast episode, please leave a rating and review. Subscribe and tell a friend.



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