Austin Perlmutter, MD, ABIM, joins Integrative Practitioner Content Specialist, Avery St. Onge, to discuss how climate change is contributing to brain disease and environmental and lifestyle interventions to improve brain immunity and reduce neuroinflammation.

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Austin Perlmutter, MD, ABIM, is a board-certified internal medicine physician, New York Times bestselling author, published researcher and international educator. His mission is to help people improve their health by targeting the biological basis of “stuckness” in our brains and bodies. His writing, presentations, podcasts, and online educational programs explore how environmental factors influence our cognitive and mental state and have reached millions. 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 is running a first-of-its kind study exploring the effects of plant nutrients on human aging through epigenetics.


Avery St. Onge: Hello everyone and welcome to the integrative practitioner podcast. You're on the go resource where we bring you closer to top industry experts, their exclusive interviews with leaders in integrative medicine. I'm Avery St. Onge, content specialist of integrative practitioner, and today we're talking about the neurobiological pathways driving brain inflammation and preventative strategies for brain conditions. We're so happy to have you as part of this community of integrative health care professionals. If you're interested in learning more about our membership offerings and how you can get access to exclusive content and networking opportunities, please visit integrative For today's episode, I'm joined by Dr. Austin Perlmutter. Dr. Perlmutter is a board certified internal medicine physician, New York Times bestselling author, published researcher and international educator. He 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. Welcome, Dr. Perlmutter, thank you so much for joining me on the podcast today.

Austin Perlmutter: Thanks for having me excited to be here.

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Avery St. Onge: Okay, so to begin, can you give me a brief overview of what you will be discussing at the symposium?

Austin Perlmutter: Sure. So I get to dive into I think the fascinating and super relevant conversation around brain inflammation. So what is going wrong with the brain's immune system? How does it get thrown into a state of inflammation? What are the impacts of this state on health outcomes? And then maybe most importantly, what are the some of the things that we can be doing to decrease the impact of chronic and otherwise unhealthy inflammation within our brains?

Avery St. Onge: Okay, so can you tell me what are the key pathways involved in immune state and imbalance?

Austin Perlmutter: Yeah, I think there are very few areas of medicine and research that are, are even comparable to what we're seeing in the breakthroughs in immunity. You know, we have often thought about the immune system. And I think many people still think about the immune system as some sort of a very basic thing that defends us against microbes and can be boosted by vitamin C. But the truth of the matter is that we have trillions of immune cells within us. And they respond in real time to what's happening in our environment. And so immunity is distributed throughout the body, it's basically found immune cells are found in basically every tissue in the body, the majority of them are located in the gut. But what's really interesting is we know there's specialized immune populations in the liver, for example, or in the skin. And as it relates to the brain, we know that about 15% of our brain cells are actually immune cells called microglia. Why all that matters is we need to reconceptualize the immune system as something that is just designed to defend us against the environment, and instead look at it as a interconnected web of data collection and modification throughout all of our organ systems. And that gives us an incredible opportunity to both understand where our health goes wrong, and where our health can go. 

Avery St. Onge: And then can you tell me more about the role of environmental and lifestyle factors on brain inflammation and immunity?

Austin Perlmutter: Sure, just as a quick background here, you know, we think about inflammation and listeners will know inflammation, especially from the context of peripheral inflammation. So what happens when we have inflammation in a joint it gets ready to get swollen, it gets painful. But what happens when we get inflammation in the brain? I mean, that's where things get interesting because we don't necessarily experience pain in our brains. I mean, you might have a headache, but maybe more likely, we're going to be talking about things like depression, and things like worse cognition, higher risk for Alzheimer's disease. So inflammation in the brain turns out to be represented in a very different way from inflammation in other tissues. Now, how does inflammation get into the brain? It's really an important question and then what does it look like? When it gets there. So we now know that when we have inflammation outside the brain, meaning in our periphery that it can get access to the brain if our blood brain barrier is leaky, we also know that the blood brain barrier has receptors for inflammatory cytokines, and that can translate that signal. And through the blood brain barrier. We also know there are parts of the blood brain barrier that may be even without any sort of diseases, more allowing of various immune markers and various immune signals to get into the brain. And I think what's really, really interesting is experiencing stress, so watching something stressful on TV can activate the brain's immune system, because those kind of stress signals get translated through nerves and into our brain's immune system. So then what does inflammation look like within the brain? Well, researchers kind of isolated a couple of major metrics we'd look at. One is activation of our microglial cells. So these are these brain immune cells that make up you know, billions of cells within our brain microglial cells can become more activated towards inflammatory state, and that seems to be critical critical to understanding brain inflammation. We also know brain inflammation is associated with a migration of peripheral immune cells into the brain. So usually, the brain shouldn't have a whole lot of blood cells, specifically, immune cells from the bloodstream getting into the brain. But when there's inflammation that may change, we also know that it's associated with damage to the brain itself, as well as with damage to the blood brain barrier. So these are, again, some of the ways that inflammation can get into the brain and what it might look like in the brain. And some of the ways in which inflammation in the brain may map on to certain outcomes that we really should be caring about.

Avery St. Onge: Now, are certain people more susceptible to these environmental and lifestyle factors impacting their brain and causing that inflammation?

Austin Perlmutter: I think the answer is yes. I mean, if you were to look at any individual person and ask how do they experience life? And is it different depending on our genes, depending on various aspects of our physiology? I mean, the answer is always going to be yes, every person has a unique experience. When we think about environmental impacts on our brain, specifically, what we now recognize is that everything we do each day is going to be translated into data that is going to reach and influence our brain. And the reason for that is if you think about what the brain does, it's kind of the central driver computer of our lives, it needs to be able to respond in real time, to data coming in from our bodies. And we think about this often in the context of kind of the stress response, we'll say, Oh, I experienced something scary. And obviously, I had a brain response, meaning I froze, I had to run away, or I decided to fight. That's the kind of the classic response to a stressor. What we now know, though, is that the brain is is incredibly responsive to data that isn't just what comes in through our eyes and through our ears. So for example, the gut brain connection is emerging as a major pathway, translating data from our food to our brain, from our microbiome, to our brain. And so that data is now understood to influence the brain's immune system. So coming back to your original question, is it true that individuals have different impacts of environmental factors on their brains and on their immune system? Absolutely, because the microbiome is different depending on who you are. And that's going to change the data that your brain gets, the tone of your vagus nerve is going to be different depending on your life experiences, which changes how your brain works, how you appreciate stress, how you experience what goes on each day, is going to be different, depending on you know, where you started from. But maybe what's the most impactful part of all this is those differences are important. But we also have the opportunity to change all of those variables each day. So if we want to have a healthier gut brain connection to programming, a healthier immune system within the brain, we know that dietary changes are playing a probably the biggest role in the makeup of our microbiome. If we want to have healthier signals coming in to program our stress pathways in the brain, which program our brain's immune system, we can make choices in the content we decide to consume each day. So yes, it's different depending on who we are. And yes, the environment has differential effects. But importantly, these are all things that are within our control to make changes to in order to better support a brain immune system that works for us.

Avery St. Onge: And, of course, brain inflammation is related to Alzheimer's and in depression and things like that. But that's obviously when it's gotten to kind of like a significant extent. Are there signs of kind of mild brain inflammation that someone should be kind of keyed into where they can start to really begin these lifestyle modifications?

Austin Perlmutter: Right, it's a good question. I mean, if we think about conditions like Alzheimer's and depression, these are kind of these are states in which things have gotten pretty that things have progressed pretty far. And while certainly we know that inflammation is correlated with depression and Alzheimer's disease, there's kind of a fallacy in this belief that because you have reached the end result, which is a diagnosis of Alzheimer's or depression, and you have higher levels of inflammation there, that nothing was happening in the decades beforehand. And I really believe that we need to destroy this idea of inflammation as just kind of a well, it gets bad enough. And then it's an issue type scenario, what we really need to be focusing is on immune balance each day, and that includes immune balance within our brains. So what are some data points that we may not be having good immune balance, which includes higher risk for inflammation in a given day? Well, there are many of them. So for example, if a person has a higher BMI, or specifically, if they have more kind of visceral fat, these are fat cells that tend to promote inflammation, that's a good signal that there may be issues going on with inflammation in the body, and by extension, that that might be affecting the brain if we have evidence of poor metabolic health. So that might mean a higher fasting insulin level a higher hemoglobin a one see a fasting glucose that's elevated, even things like a higher uric acid level. These are indicators that there may be metabolic imbalance, which correlates with higher rates of inflammation. Similarly, if we're experiencing high levels of stress, if we feel constantly stressed, if we feel like we're having trouble sleeping, if we feel anxious all the time, this is an indication that our HPA Axis may be out of whack. Now, that's an entirely separate conversation as it relates to why is that the case and what goes wrong with our stress pathways. But the important piece to understand here is a chronic dysregulation. Stress pathways correlates with a higher rate of inflammation. And that may include inflammation in the brain. There's other things that we can think about as far as just general exposures. So if we tend to eat a diet that is high and ultra processed food, that is an indicator that we may be promoting inflammation in our bodies and in our brain. So ask yourself on a given day, are you eating mostly foods that are real foods? Are you eating mostly foods that your great great grandparents wouldn't have recognized? That's an indicator that there may be issues with inflammation if you tend towards a more Ultra processed diet. Similarly, if you're a sedentary person, if you don't move your body an indication, there may be higher levels of inflammation. And one of the specific data points that I'll be talking about in our presentation, is the idea that the air that we breathe is a major risk factor for immune imbalance, including immune imbalance in the brain. So if you tend to be consuming or breathing in a lot of polluted air, what are some indications there? Well, do you live somewhere where wildfires are a big issue? Do you regularly use scented candles in your home and air fresheners in your home? Do you cook on a stove that isn't ventilated? These are all indicators that you may be exposed to higher levels of air pollutants that have been linked with higher levels of inflammation. So there are many things that we can think about. And I think the bottom line to all of this is, all of us need to be paying attention to this. It isn't something where we say Oh, well, only certain populations need to be worried about brain inflammation. Only people who have experienced symptoms of low mood, or cognitive decline need to be worried about brain inflammation. This isn't a binary thing. It's something that we need to be paying attention to over the course of our lifespan. So again, everybody really needs to be thinking about this stuff.

Avery St. Onge: And then you kind of started to mention this, but what are some specific lifestyle modifications to help improve neuro immune health? Sure,

Austin Perlmutter: I think there are so many things that we can do to improve our neuro immune state. And it all starts from the understanding that the way that your brain's immune system is structured is basically to listen to what is happening in your environment and to respond in accordance with that data. If we think about what inflammation is, it is the body's response to a danger signal. And in a perfect world that only comes up when there is an actual danger. So if you had a bacterial infection in your brain, you really would want inflammation because it would help to kill those bacteria. Now, we don't want chronic inflammation in our brains. And so to remove the chances, that becomes likely, we need to decrease the danger signals in our brains so that our brain's immune system doesn't get thrown out of whack. So what are the things that we can do to help decrease those danger signals, there are a number one of them would just be the stress piece, you can't just not have stress, we actually need a little bit of stress. It has a hormetic effect, which means it's good for us. But stress mitigation practices ranging from mindfulness to meditation to nature, exposure, even to exercise are all great ways to tamp down stress pathways within the brain, which in doing can help suppress chronic inflammation in the brain. As I said, one of the things I'll be talking about in the presentation is the role of air pollution. I think it's one that we've hugely missed as far as a major impact on our overall immune state and brain immune state. And a couple of real quick tips that I would give everyone is number one stop using air fresheners. Air Fresheners are among the most toxic sources of air pollutants in the world today, because they are concentrated doses of basically these VOCs these volatile organic compounds, as well as PMS, which are particulate matter, all of which have been linked to worse brain immunity, worse overall immunity worse overall health. So don't use those air fresheners in your home, definitely don't get those little dangly trees in your cars. And really just be thinking about what are you putting into the air that you're breathing. Another one on the air pollution front is to be thinking about when we're cooking to make sure we're ventilating. There's a lot of controversy right now around gas stoves, it does turn out to be the case that one of the most potent sources of air pollution in our lives is what happens in our homes, not what happens outside our homes. And using cooktops that are not ventilated is among the top sources of indoor air pollution. There's other ones that I'll be talking about as it relates to diet as it relates to substances for example, alcohol, is correlated with higher rates of neuro inflammation in certain studies. So making sure that if we do consume alcohol, that we're limiting that use. But the bottom line here is these are many of the kind of core lifestyle measures that myself and many others have been advocating for, for a long time. And inflammation or immunity, I should say, is kind of a compounding effect of our choices that we make each day. So while that means there's probably no single thing that you're going to do that is going to throw your brain immune system out of whack, and also means that in order to get it into a state of relative balance, it's kind of the combination of a number of things that we do each day that matters, rather than just saying, Well, I ate a superfood today. The one exception might be if you are somebody who smokes, that's probably the single most important thing you can do to help lower the effects of chronic inflammation in your body is to work on smoking cessation. 

Avery St. Onge: And then I mean, we've been talking mostly about prevention here. But Can these lifestyle modifications, is there a potential for them to be targeted interventions for people who are already experiencing brain disorders?

Austin Perlmutter: Sure, I absolutely think that that is the case. And if you're going to look at the spectrum, but what we can do, it's important to realize that we're already using a lot of pharmaceuticals for brain immune function. So thinking about the fact that you know, 45% of people over the age of 60, taken daily aspirin, well, what is that it's actually an immune intervention. It's actually a neuro immune intervention. If you've ever taken, for example, an Advil because you've had a headache, that is a neuro immune intervention. And so it kind of goes on from there. So steroids that we might take are neuro immune interventions. We also know that, for example, the GLP one agonists that have become very popular recently, may work in part through their effects on the brain's immune system. So that's obviously the one extreme that's not lifestyle intervention, as much as it's pharmaceutical intervention. But the idea here being that many of our lifestyle interventions, so dietary change, increasing exercise, getting better sleep, our neuro immune interventions is actually one of the ways that these things may work is thinking about what happens to our bodies, and to our brains. When we engage in these lifestyle factors. To really drive this point home, I think it's important to understand that when what we do, what we think, what we say how we act, these are all reflections, obviously, of what happens within our brain. And we've kind of had this idea that okay, fine. You know, our neurons really matter. We want healthy neurons. But if we were to ask the question of what is it that keeps our neurons healthy, or drives them towards a state of poor health, the brain's immune system is at the top of the list as far as what's going on that is actually teaching our neurons to be healthy or driving them towards poor health. So all of these things that people have been talking about for years that had been discussed at IHS for years, as far as brain healthy interventions, they work in part by reprogramming the brain's immune system. So I think that whether people were aware of it or not, so many of the things that have been recommended from a lifestyle perspective are in fact acting on neuro immune pathways. Now, what excites me is the ability to get a little bit more targeted in that. So if we could understand that a person's brain inflammation may be driven by metabolic dysfunction, then we could say, well, maybe in this case, what we want is a plan that targets the metabolic dysfunction that might be driving the inflammation. So it might be a dietary strategy, for example, that is more of a Keto dietary strategy, which we know tends to be good for people who have significant insulin resistance and basically high levels of circulating glucose. And another person's case, if their brain inflammation is being driven by chronic stress, well, maybe it for them, it's psychotherapy, maybe for them, it's going, you know, and doing more mindfulness each day. So I think the neuro inflammation can actually be an end result of many of these other pathways and one of the roles for The clinician is to try to figure out what are the things that are driving that pathway and therefore making interventions a little bit upstream of what's happening at the level of our microglial cells? 

Avery St. Onge: Well, those were really all the questions that I had for you, Dr. Perlmutter, do you have anything else that you'd like to add?

Austin Perlmutter: I would just say, I'm so excited to be getting back together with everyone at IHS and to be having some of these conversations around the future of health, the future of brain health. One of the things that I haven't mentioned so far is that one of the other things that influences brain immunity is Myo kinds. And we've been hearing a lot about this. But basically, the idea that the reason exercise is so beneficial to our brains, may have to do with the fact that our muscles produce immune signals that can go into our brains and change the way that our brains function. So we've often thought about muscles as kind of just these metabolic repositories of energy that gets burned. We build muscle strength, and that's good for us. But the truth of the matter is that our muscles are actually these immune active organs that are acting on the brain's immune system. So this is really, really interesting and new information. I'm really excited to be talking about it. Yeah,

Avery St. Onge: I'm excited too. Well, thank you again for joining me today, and I'll see you in February. 

Austin Perlmutter: Fantastic. 

Avery St. Onge: Thanks for listening. We'd like to thank Scott Holmes and Kevin MacLeod for providing us with our theme song. Be sure to visit our website integrative or send us an email at [email protected]. Remember to like and subscribe to our show. We'll see you next time.

Editor's note: Transcripts are autogenerated