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REPLAY: Neuroinflammation: Impacts on Immunity, Behaviour and Brain Function with Dr. Adrian Lopresti and Dr. Austin Perlmutter

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REPLAY: Neuroinflammation: Impacts on Immunity, Behaviour and Brain Function

Dr. Austin Perlmutter, neurobiology, mood and decision-making expert, joins our ambassador Dr. Adrian Lopresti as they explore the biological basis of “stuckness” in the mind and how the brain is influenced by inflammatory/immune triggers which results is certain behaviours and health outcomes. 

Together they discuss the relationship between sickness behaviour, neuroinflammation and their effect on the brain leading to our inherent tendency to return to “default”. Nature VS nurture is discussed where exposures from foetal development, childhood trauma and genetic influences can impact our mental and cognitive flexibility much later in life.  

Austin explains “disconnection syndrome” a modern conundrum where our brains tend to latch onto impulsive behaviours leading to cognitive decline. It’s not all doom and gloom as Austin and Adrian bring practical solutions to the table in the form of simple lifestyle adjustments that promotes behavioural change and reduce neuroinflammation. 

Covered in this episode

[00:31] Welcoming Dr. Austin Perlmutter
[01:42] Preventing chronic disease and reduced brain function
[05:32] Sickness behaviour and the impacts of inflammation on the brain
[08:48] How genetics and environment predispose us to increased risk of brain conditions
[12:46] Does early life trauma increase our risk of developing mental health conditions?
[15:28] The disconnection syndrome 
[18:57] Chronic stress induces brain atrophy
[24:02] How inflammation impacts immunity
[29:00] Connections between inflammation, impulsivity and decision making
[35:07] Effects of inflammation on sleep and neuroplasticity
[41:05] Food for brain health
[48:34] Supplementation to improve brain function and reduce inflammation
[51:24] Implementing lifestyle changes and  resources for practitioners
[56:07] Thanking Austin and final remarks

Key takeways

  • Early manifestation of brain health issues can be due to exposures that start at foetal development, which is not in our control. What is within our control is helping patients realise it’s never too late to start prevention – especially where early signs are observed. 
  • The brain is influenced by the immune system where sickness behaviours are the likely outcome of inflammation activating the brain’s immune system. With chronic inflammation this looks like reclusive behaviours, turning to comfort foods and making decisions that are not conducive to long term brain health. 
  • Risk factors in modifying inflammatory/immune related sickness behaviours can be contributed to genes, our exposures to toxins in the modern environment, lifestyle factors contributing to stress and diet.  
  • Major stressful events, like childhood trauma, can be a trigger that permutates risk for developing poor brain health. These traumatic events contribute to epigenetic switches that instigate low-grade longer-term issues. Understanding there are accessible interventions which can be implemented to lower the risk of chronic inflammation in an important point to realise for practitioners. 
  • It’s important to recognise “disconnection syndrome”. The concept of seeing, hearing and having everything but still not being satisfied and seemingly disconnected to the world around us leading to the perpetuating need for instant gratification and behaviours that lead to feeding the dysregulated brain activity. 
  • There’s much more to mental health than just neurotransmitters. Emerging evidence is showing low grade chronic inflammation has impacts on the immune system that change thought processes and emotions. Observations in mood and immune markers show a correlation between these markers and depressive symptoms. 
  • Recognising that some of our lifestyle recommendations regarding physical activity and dietary change may not be so helpful for improving brain health is important. One integral aspect is sleep – this is the most impactful habitual change that one can implement which augments brain health and function along with hormones, neuroplasticity and our immune system. For some people short amounts of sleep deprivation may even increase their brain derived neurotrophic factor that aid with neuroplasticity.  
  • Main dietary recommendations for general brain health support is a Mediterranean style diet that is well researched for improving depressive symptoms and supporting diagnosis of Alzheimer’s. This may look different from person to person but the main premise to remember - eating less processed foods. This means omega 3's from fatty fish, nuts and seeds, PUFAs from olive oil and whole foods like eggs and avocado. Protein rich foods like fish, meat, legumes and poultry and carbohydrates coming from whole (ancient) grains and whole fruit and vegetables that also provide polyphenols for brain health benefits. 
  • Reducing brain inflammation through supplementing with vitamin-D, omega-3's, and specialised pro resolving mediators can be helpful. Specialised pro resolving mediators have a unique relationship with the immune system and inflammation over that of omega 3's in their specific function to resolve chronic inflammation and not just dampen it. 
  • Up to 40% of our daily decisions stem from habits and the other 60% can be through influence. Implementation through mutual agreement on what is achievable and forming those habits beneficial to the patient/practitioner relationship and ultimately, patient health outcomes.  

Resources discussed and further reading

Dr. Austin Perlmutter

Website: Dr. Austin Perlmutter
Austin's newsletter

Books and resources

Brain Wash by Dr. David Perlmutter and Dr. Austin Perlmutter
Good Habits, Bad Habits by Wendy Wood
The Power of Habits by Charles Duhigg
Atomic Habits by James Clear


Research: Inflammation Predicts Decision-Making Characterized by Impulsivity, Present Focus, and an Inability to Delay Gratification (Sci Rep. 2019)
fx Medicine Article: Mediterranean Diet for the brain
Article: MIND diet review (Harvard School of Public Health)
fx Medicine podcast: Continuous Glucose Monitoring with Dr. Michelle Woolhouse and Jessica Turton


Adrian: Hi, and welcome to FX Medicine, where we bring you the latest in evidence-based, integrative, functional, and complementary medicine. 

FX Medicine acknowledges the traditional custodians of country throughout Australia where we live and work, and the connections to land, sea, and community. We pay our respect to their elders, past and present, and extend that respect to all aboriginal and Torres Strait Islander people today.

With us today is Dr. Austin Perlmutter, a board-certified internal medicine physician, New York Times best-selling author, educator, and consultant. Austin's focus is on helping identify and resolve the biological basis for stuckness in the body and the brain. He strongly believes in the healing power of nature and food to improve brain function. 

Austin lectures internationally, is the host of Get The STUCK Out podcast, and has co-written a terrific book Brain Wash, which covers a range of tools necessary to help people think more clearly, make better decisions, strengthen bonds with others, and develop healthier habits. 

So, welcome to FX Medicine, Austin. Thanks for being with us today.

Austin: Thank you for having me. I'm excited for the conversation.

Adrian: Terrific. I know that you're a very strong advocate of nature, and diets, and lifestyle approaches to improve brain function and overall health. However, this is not really a heavy focus of many medical physicians. So, can you tell me a bit about how you developed an interest in this area?

Austin: You're right. It's not a focus, and I think the bigger picture is that effective preventive medicine is not a focus for most people. The way that our entire planet has, in essence, structured its concern about medicine on the whole, and this isn't universal for every person in every location, is the way we've moved towards structuring our lives. And that is: do what we want to do now and deal with the consequences later. That has turned out to be an absolute disaster as it relates to our health. We're seeing, as you know very well, an absolute uptick across the planet in people developing chronic and preventable diseases that lead to a dramatically lower quality of life and lead to an earlier death. We've seen in the United States, people are dying earlier in the last two years. That was even pre-pandemic. So these are really scary things. So, that's, I think, the starting point.

But where I've really dedicated myself in the last two years is to narrow in on where I think we benefit most from focusing, and that is understanding what does prevention mean as it relates to brain function? And maybe at a slightly more nuanced level, how are we capable of understanding our brain function on a moment to moment basis? Because if you look at these issues that we face, the unhealthy diet, the not exercising, the unnecessary exposure to stressors, these are a reflection of our decision-making. So, if we can get to the core structure of how our brains work, understand what is moving them towards making worse decisions, towards worse mood, and reclaim some of that brain wiring for our own benefit, I think that's the single most impactful thing that we can do as a society to move ourselves towards a better tomorrow.

Adrian: Absolutely. When you talk about prevention, are you talking about in childhood or do we really need to start things as early as then or later on?

Austin: It's a great question. I guess, what do I mean by prevention to start with? So, we know there are millions of people already around the world experiencing brain conditions, and by millions it should be really hundreds of millions, if not over a billion, or even many billions of people who are experiencing brain conditions like stress, anxiety, depression but also who are experiencing cognitive decline. So, not just Alzheimer's but mild cognitive impairment. We like to think about, well, as you age, your brain just isn't as good as it used to be. That's not necessarily true. These things are a reflection of what we do in the decades leading up to developing something like Alzheimer's.

Alzheimer's is a disease that primarily affects people in their older ages. But what we're now learning is that certain people are developing it earlier and that we start to develop risk factors for Alzheimer's disease much earlier, even in our 20s. But to take that into the bigger perspective, so when we bring in mental health and cognitive issues, both of which are brain health issues, and ask where do those things begin? Well, you can go very early. You can go prenatal. You can start to understand how a maternal diet, meaning what mom eats when we are in the womb is influencing our brain health.

Adrian: Yes.

Austin: So, the reality is the place where this starts is wherever a person can handle starting it. If you could handle starting it prior to birth, that's a great place to start. But there's never a bad time or place to start. Each of us is capable of taking steps today to create better brain health for today and for tomorrow, and I think that's the empowering message. It's never too late, and it's certainly never too early.

Adrian: Yeah, absolutely great. Certainly, the research does show that the earlier we intervene, or the more effective the treatments are going to be, or the prevention of disease is going to be, but certainly it's never too late to stop. I agree with that 100%. 

When you talk about brain health, I know you've done a lot of work on inflammation, and the immune response, and how that can affect the brain. Can you tell us a little bit about how inflammation affects the brain and the processes there?

Austin: For sure. I know this is something that you know very well also, but my interest in this came from the basic question of “What are the things that are most strongly influencing our brain function as it relates to our moment-to-moment thinking, as it relates to our long-term health?” Because usually I feel people have an understanding that our brain health is really important mostly when things go wrong. So, if we get sick, for example, if you come down with the flu, you might experience brain fog. I know I certainly do. You say, "Oh, well, I'm sick. I have brain fog," and now I worry about it, and I think, "Okay, what can I do to improve my health?" Or, if you start to develop memory issues as you age, you might think to yourself, "Oh, well there must be something going wrong with my brain."

But for most people and most of the time, we don't think about the fact that the brain is dynamic, that moment-to-moment, how we think and how we feel is a reflection of a ton of different systems that are constantly evolving within the brain. One of those turns out to be the immune system. So, let me go back to this example I gave for a moment because I think it's really impactful. 

Let's go back to a time where we experienced brain fog when we were sick. You know, this is what many people, if not the majority of people experience. If you have an illness, you probably aren't going to want to go out and take a math test. You're probably not going to go out and want to hang out with your friends. You're probably not going to go want to go to work and really think through some complicated problems. That is a reflection of what happens in the brain when we get sick. And what happens when we get sick? Well, you have changes in the immune system.

So, this is called “sickness behaviour.” It's a whole cluster of changes in how we behave that comes along with getting sick. The reason why this is about to happen is because an upregulation in inflammation — which is a change in the immune system that happens when we're sick — changes our brain function. It's such a powerful example of a more intense version of what is happening to all of us moment-to-moment, which is that our brain's immune system, and especially our brain's level of inflammation, is influencing how we behave, is influencing how we see the world. 

When we start to appreciate that inflammation, basically higher levels of sustained inflammation appear to push our brains towards things like depression, making worse decisions, having worse memory, higher risk for Alzheimer's disease, and that there are things that we can do today to help reduce that risk, you create a closed-loop system where you appreciate the value of lifestyle factors like the food you eat, the exercise you get, the sleep that you get as being able to contribute to a better brain by way of that immune system.

Adrian: Obviously, you mentioned sickness behaviour and when you've got the flu, there's acute inflammation that occurs, which is not necessarily a bad thing. But then you've got your chronic inflammation that occurs that may be related to a whole bunch of factors, but what makes somebody develop chronic inflammation and therefore brain-related conditions? And then you've got someone else who might be engaging in the same behaviours but not necessarily suffering from any neurological conditions or any mental health disorders. What's the difference there, do you think?

Austin: This is a really good question, and it's something that I think all of us are still trying to better understand. So, why is it that one person can eat a certain food and feel like crap, and another person eats that food and feels great? There are tons of reasons for this, but the very basic reason is that each of us has a different body. Each of us has a different set of genes. Each of our gene sets are being expressed differently. And so it's certainly not as straightforward as saying, "Well, you got sick, you have inflammation, you will experience brain fog," because what we've seen so clearly, especially in the context of the pandemic, is that when two different people even who live in the same house, even who share genes, are exposed to the exact same infection, people can have dramatically different changes in how they feel as a result of that infection.

So, I think there's a couple of things to consider. I mean, the very basic way to stratify this is what you get from your genes and what you get from your environment. I mean, this is kind of the way that I was educated is you get certain genes. Those genes predispose you to certain things. APOE4 being a good example on Alzheimer's to group that disease where, if you have two copies of that gene, it increases your risk for Alzheimer's by about eightfold. But there's nuance there too. What we're now learning through epigenetic science, which is another can of worms, it's not just the genes. It's how our environment acts on the genes that matters.

The other part of this, of course, is that our environment is going to change our physiology in such a way that we may be more or less predisposed to developing something like chronic inflammation. I think a good example of where this plays out is in the context of, let's say, diabetes. So, there is absolutely, in certain people, a strong genetic predisposition to developing diabetes, and so this would be something like type 1 diabetes. Whereas, these are people who lose the function of their pancreas. They're insulin-dependent. Certainly, some lifestyle factors may play a role in that. However, this is something that usually comes on in childhood, so it's far more genetically determined.

But then you think about the context of diabetes around the planet today, and 95% of people who have diabetes do not have type 1 diabetes. Rather they have type 2 diabetes. Here, what you see is, I believe, the reality for most of us, which is that the genes may play a role in risk for developing a condition. So, there are certain genes that may predispose us to developing type 2 diabetes, but the real major factor is not the genes. Why do I say that? It's because when you look at rates of developing type 2 diabetes and how they've changed over the decades, they have skyrocketed. We have so many more people who have these conditions today than had it a few decades ago. Our genes didn't change in a couple of generations. Rather, what changed was our environment.

I think it's the exact same thing as we look at increased risk for conditions like Alzheimer's disease. As we look at prevalence rates for conditions like depression, what we have is certainly a genetic predisposition, but it's really these environmental and preventable factors, things that range from our diet to, again, our stress to even the air pollution that we consume that are acting on those genes and changing our risk for developing these conditions.

Adrian: So, I suppose that, certainly there's genetic factors, and you also mentioned earlier, when we talked about prevention, that even our exposures during childhood or even en utero, they might also predispose us to how we respond to inflammation and lifestyle practices, and things like that. So, I know if people are exposed to abuse and trauma at an early age, that can make them more susceptible to a whole range of different conditions. So, that is obviously a factor too, wouldn't it be?

Austin: That's right. I think where we're seeing the strongest signal for that would be in something like early life trauma and subsequent risk for developing depression even decades later, where people who have experienced these adverse childhood events are at significantly higher risk for developing depression. And so there is a question of “How does this happen?” And there are a number of potential pathways by which this may develop. One actually, interestingly enough, may be inflammation. It may be that those early childhood traumas, by way of stress that converts into chronic inflammation, predisposes people to worse mental health later on.

It may also be that trauma is actually going to translate into an epigenetic mark that changes the way our genes are used. And where myself and some others have been spending some time looking recently is, are there interventions that we are capable of instituting that are able to reverse some of this epigenetic marking by way of things like nutrition? So, I know that's kind of a deep cut into the subject, but point here being, when you look at the variables that contribute to our poor brain health today, it used to be you'd say, "Well, these are the ones that are within your control, and these are the ones that are completely outside of your control, and they're genetics." There are certainly conditions that are almost exclusively driven by genes as it relates to bad brain health.

However, for most people and most of the time, that is certainly not the case. Even if there are genes that predispose to a higher risk for developing a condition, there's still a ton that we can do, both by traditional things. Let's lower inflammation. Let's eat a generally healthy diet. Let's get rid of some of the fat cells that might be contributing to dysfunction in our brains. Maybe let's do some things with the microbiome. But now what we're recognising is, through these epigenetic pathways, we may be actually able to change the way the genes function at the very core of this puzzle. 

So, it just opens up the conversation about having more tools, and there are less things that are inaccessible to us as it relates to helping to prevent, and even in some cases, treat these conditions.

Adrian: You've written a terrific book, Brain Wash, and in that book, you talk about the “disconnection syndrome.” Can you tell us a little bit about what that is? And is that potentially a driver of the inflammation?

Austin: So, I wrote this book with my dad, David Perlmutter, who's a neurologist, and we published it back in 2020. The basic premise of this is when you look at a representation of why so much is going wrong as it relates to what we see in the world today? Whether it's international wars or people not prioritising their nutrition, or issues with relationships. We can kind of look at what is happening within the brain as a representation of so many of these problems. And what we focused on here was this disconnection that occurs at the level of our biochemistry that is represented at the level of our functional connectivity or connectivity within the brain, how our networks work, and that it is represented and driven by a number of activities that we see more highly represented in the modern world.

And so there are several of these that we talked about. Some of these we've already alluded to. So, chronic inflammation and chronic stress are two of the things we called out. We also talked about the relationship between this brain disconnection and impulsivity. In essence, making more impulsive choices, behaving more impulsively, which is a huge issue. Also, in that vein, we talked about the connections between our brain function and our increasing reliance on instant gratification as a way of functioning in the modern world.

So, what we hope to do was look at from a behavioural level, how are we acting, how are we spending our days, and what does this translate into both as a result of this within our brains, and what does it represent as far as what is happening within our brains? I think that's really important because we see today that the average adult, at least in the United States, and I believe it's the same where you are, is spending around 11 plus hours a day engaging with media, with screens in a given day.

Adrian: Yes.

Austin: So, specifically with media, but when you come to screens, we're spending nine plus hours of our day on screens. Whether it's computers, or TVs, or our phones, people are spending two-plus hours a day on their phones. A lot of that is on social media. Regardless of a person's opinion, I believe, on whether social media, our phones are good or bad, we have to appreciate that there is a dramatic opportunity cost. What are we losing with our over reliance on media for filling the gaps in our day? Why are we so consumed by these things?

So, again, I think we can try to look at some of the pathways within our brains that are being changed by these types of modifications, and how we spend our time, and how changes in our brains are actually driving us to do these things more, and how this leads to a vicious cycle that we described in the book as far as disconnection syndrome being a self-perpetuating system where we develop these changes in our brain as far as how they function that are pathological, that lead us to do more of the things that are unhealthy, and subsequently drive our brains further towards that state of pathology.

Adrian: So, is it, engaging in these behaviours, they then obviously have an impact on our brain? Are there different parts of the brain that are affected by different behaviours and inflammation? How does it all work from a neurological perspective?

Austin: Where I'd like to start is just for everyone to appreciate the importance of our brain's dynamic nature. The concept of neuroplasticity is the technical version of this, but the main point is I believe all of us have this bias towards understanding that certain things in our lives change rapidly. So, you look outside the weather, sometimes it's hot, sometimes it's cold, sometimes it's cloudy. We all understand that pretty well. The sun comes up, the sun goes down. We know that each day these things change. We don't really worry about that. We assume that. We plan for it. We bring our raincoats with us but it's sunny. It's incorporated into our lives.

As it relates to our brains, I think we have a very big misconception about how dynamic it is, because the reality is our brains are perpetually in motion, and that means that each moment of each day, we are changing the structure and function of our brain. That's really important to appreciate because it means you can change for the better or for the worse how your brain is being wired and how your brain is functioning.

So, the question as to do certain things overlay more on certain parts of the brain, I think, is a very good one. What we know is that certain parts of the brain are more highly receptive to and modified by environmental influences. So, when you look at what happens in Alzheimer's disease, there are several pathologic changes, amyloid health, but what you see at a more macro level is that you have a relative atrophy or shrinkage in a part of the brain called the hippocampus. That's not a good thing, because the hippocampus is key to converting our experiences into long-term memory. So, this helps to explain why people with Alzheimer's disease have memory issues. 

You also see a number of other areas of atrophy, but one of the predominant areas of atrophy is the prefrontal cortex. This part of the brain has a number of tasks but maybe most importantly is involved with higher-level functioning. It's helpful as far as taking emotional data and converting it into more rational thinking. It's helpful as far as making well-thought-out decisions. It weighs the pros and cons. It's really essential for us to function as high-level individuals. So when you see atrophy there, that's a real big issue for these higher-level functions.

So, this then gets to the question of what are the things that we see that correlate with these types of atrophies? And one of the strongest correlates is actually chronic stress. So, chronic stress correlates with atrophy of the hippocampus. It also correlates with atrophy of the prefrontal cortex. It also correlates with a decreased strength of signal between the prefrontal cortex and the part of the brain called the amygdala, which involves emotional reactivity and emotional processing. So, this chronic stress here seems to be really important.

What are the mechanisms by which that chronic stress exerts this damage? Well, one is actually that it made you so through inflammation. In addition to this, if you were to look at the brains of people with depression and you were to image for a specific marker of inflammation - this is actually the case in Alzheimer's as well - if you were to look for this specific marker of inflammation, what you'll see is evidence for increase in this inflammatory marker in these parts of the brain, the hippocampus, the prefrontal cortex, as well as a couple of other areas of the brain like the insula, and the anterior cingulate.

That's important because if there's increased inflammatory activation in those parts of the brain, that may help tell us why, in conditions like depression, we see issues with certain types of cognitive problems beyond just feeling low. What we see in people with depression is changes in their bias, what's called a negativity bias where they change the way they see the world, where things are a bit more negative. What we actually see is another really interesting correlate of changes in brain activation, which is something called temporal discounting, which is a fancy way of saying people make more impulsive choices. That is something that is seen in a wide variety of brain conditions ranging from Alzheimer's to depression.

So, is that a direct relationship to or is that driven by this inflammation? We don't know exactly. What we can say is inflammation seems to target these areas of the brain that seem to be most involved in things like depression and Alzheimer's disease. We're also now learning that certain interventions, even conventional antidepressants for example, may work in part by lowering those levels of inflammation. So, there's a lot to be said around this but to be clear, we're still trying to understand if it's specific parts of the brain that inflammation is specifically damaging because it's just so hard to actually image or measure inflammation in people's brains.

Adrian: Yeah, you're certainly not going to get a lot of volunteers to get into the brain and see what's going on there. So, I know that there's a relatively good body of research that even if you induce acutely inflammation, it changes the way that people think. They can be more sensitive to social rejection. They can have a more negative bias. So, this is then potentially the inflammation might be affecting different parts of the brain and also the communication between different parts of the brain. Is that potentially what's happening?

Austin: That's right. You've kind of hinted here at what I believe to be one of the most important and new understandings as it relates to neuroscience research, because up until pretty recently, there wasn't really a strong understanding that what was happening in the brain's immune system was all that significant outside of very explicitly immune-related conditions. So, if a person has an abscess in their brain, some sort of a parasite, a bacteria has gotten in there, certainly people would say, “Yes, inflammation is not good for the brain.” There is inflammation here. If you did a biopsy, you'd see neutrophils and other immune cells. It would be very clearly inflammation as a result of infection.

But what's only happened in the last couple of decades is the understanding that inflammation in the body, even at levels lower than what you would see with certain diseases, correlates with changes in how we think and how we feel. For me, really this research starts a couple of decades ago, because it was at that point really in the early 1990s that researchers started to show that there was a correlation between mood and immune markers in the bloodstream, not in the brain. What they showed is that people who had higher levels of certain types of immune cells, specifically white blood cells, had higher rates of depression. But what they also showed is that people who had more inflammatory tendencies had higher rates of depression.

So, this was kind of the start of the integration between neuroimmunology and psychiatry. It certainly progressed a long way since then, but it was the idea that what happens in your immune system, even your immune system outside the brain is influencing your thoughts. And that's been carried through in a number of other studies. You alluded to this, which is if you give healthy people something that increases inflammation in their bloodstream, you will change how they feel and you will change how they think. So, I don't think many people would say this is 100% a causal interaction. People for a good reason have hesitation around saying X causes Y, but there is a very strong and building case for the idea that when you do things to a person's immune system, specifically when you increase inflammation in their body, you can reliably, not in everyone, but in certain subsets of people, create certain reproducible effects.

And so what are those effects? Well, I think the strongest case is that people tend to feel symptoms of depression. They, as you said, have social withdrawal. They feel lower mood. They feel less motivated to do things. That's in healthy people who are injected with a molecule called LPS, which is found in bacteria, that increases inflammation. So, it's really interesting stuff that's developed. And there's also research that looks at, do people with depression have higher rates of inflammation? And by and large, what the research would show is for the average person, there's a higher rate of inflammation if they have depression. If you have higher levels of inflammation, you probably will have a harder time at achieving treatment or efficacious treatment, meaning that higher inflammation predicts treatment resistance.

Adrian: Yes.

Austin: So, what we're talking about here, as it relates to the mood, is a brand new portal into understanding one of the major variables that drives our mental health. It's not just about serotonin. It may not be much about serotonin, actually it turns out, but it may be more about how our immune system is playing this kind of dynamic song, pressing the keys of our neurons and leading us to feel one way or another. So, it's really interesting stuff. 
The other little piece here, which we could talk about more if you like, is that beyond just mood, we're understanding that inflammation is correlating with how we make choices. So, moment to moment, your level of immune activation is influencing how you make decisions, whether you make a long-term oriented decision or a more impulsive choice. And really the most interesting thing about all of this is, at some point, you understand that these conversations get to the very essence of who we are, what we define as our identity, how we look at ourselves, that those things are a reflection of how something like the immune system is acting on our brain.

Adrian: So, is it that inflammation will more likely lead to impulsive decision-making? Is that what you're saying?

Austin: Yeah, so there have only been a few studies in this, but they have been in relatively well-respected journals. I'd say maybe the most notable of these are two that just came out in the last few years. One was in Nature's Scientific Reports, and it was called ‘Inflammation Predicts Decision-Making Characterized by Impulsivity, Present Focus, and an Inability to Delay Gratification.’ In essence, what they did is they looked at their levels of inflammation, and they created a score from that. And then they looked at people's levels of impulsivity on test-taking. What they found is higher levels of inflammation predicted people making more impulsive choices.

That was followed up by a study, or actually a study that came right before it, which they did some things to participants, so they stressed them in order to increase inflammation. It's funny the way that you stress people in these things is you put them into an environment where they have to report to a panel of experts, and they have to do some hard thinking right in front of them. It is very stressful, having done these types of things before, but I feel bad for the people in these studies. But in any case, they do this, they increase levels of inflammation, and then they test their decision-making and found that when people had an increase in inflammation, that they had more impulsive decision-making.

But I just want to stress here for a second, I guess no pun intended, that talking about impulsivity seems like it's not a huge deal, right? Well, you're a little bit more impulsive. What does that matter? But if you look at, in essence, every major decision that you'll make in the course of your life, I think it's important to ask, “Is this a decision that would benefit from me being able to weigh the pros and cons, or is a decision that benefits from me being reactive and just going real quickly with whatever feels right and not worrying about it anymore?”

There are certain decisions in life, I agree, that we may benefit from going with the impulsive choice, the fight or flight, the stress-induced response. But for the big things, for example, how we navigate our relationships, how we navigate our jobs, how we choose what to do in the course of the day, whether it's going to the gym or sitting on the couch and eating potato chips. Being able to make a long-term oriented decision, which prioritises future self in addition to present self as opposed to just what the me right now wants is incredibly important. So, these things we're talking about as far as impulsivity actually matter a lot for a lot of the things that people tend to care about.

Adrian: I'm just thinking like, if you mentioned the amygdala being part of the brain that might be triggered, but if you're amygdala is hypersensitive, it's going to really impact on the decisions that you make, and that may not necessarily be for the right decisions certainly in the long-term.

Austin: I think the way that I would phrase it is what tends to happen in certain contexts, maybe stress being the best example of it, is that the person seems less able to bring in additional and often important information. Instead what it does is it reverts to basically tunnel vision and impulsive choices. In some ways, there are situations in which that is helpful. So, I'm sure people have given other examples of this on the podcast, but imagining that you are in a very real danger, whatever sort of threat it is, there's a real scenario in which you want to have those more primitive impulses be able to take control. So, maybe it does make sense to just literally run away and not think through, “Well, what are the pros and cons for me running away right now?”

But for the vast majority of decisions that matter, you really want your prefrontal cortex to be engaged. What we talk about in the book is that there are just so many things that push our prefrontal cortex to being offline where we're either just mindless and so we're not engaged in that higher-level thinking. A good example of this might be, if you're just scrolling on social media for two hours, it may not be that you're necessarily doing something bad for your body, but without your higher-level thinking online, because it kind of goes to sleep so that you can just randomly scroll, you're not necessarily as engaged in the world. You're not thinking about stuff that is meaningful. Maybe more importantly, if and when there's a pitch for you to consume some unhealthy product, you may not be ready to weigh the pros and cons of it, because again, you're just in a more reactive state. And part of that actually does stem from there's a lot of stress that is intrinsic to the media we consume today. Probably a better example than social media, granted some people have the intense sense of stress, especially when there's social comparison involved on social media, but in watching and listening to the news. That is an incredibly stressful experience, which as we've discussed, leads to people's prefrontal cortex going offline.

So, what happens next? If we experience a high level of stress, we revert to more habitual, lower-level behaviour, which would mean, for many people, reaching for the unhealthy food. Which would mean instead of doing what we had already planned to do, going to the gym, going for a walk outside, spending time catching up with our spouse or partner hearing about their day, we need to do something to help cope which again could be food. It could be going on social media. These are things that our brains do because they're habitual. In the context of our prefrontal cortex not being able to be in that moment to be present with it, we start to do more of these things.

So all of it tethers together, but the sum result is we spend more of our time each day doing things that tend to be more habitual, that tend to be less beneficial to our long-term health, and that actually the things we do, meaning unhealthy food, not exercising, not really engaging in healthy relationships, are the exact things that tether most closely to risk for having worse brain function. So, you get it on both ends, first because the thing itself led to worse brain function and then because the decisions you make because of those unhealthy things lead to worse brain function.

Adrian: I mean, I've done a lot more research recently looking at, not only the changes in the lifestyle behaviours that we're engaging in and the diets and so forth, but also the timing, the circadian rhythm. I know that there's often dysregulation in that circadian rhythm. Sometimes it's not just what we're doing, it's also when we're doing it, and potentially we might be engaging in pro-inflammatory behaviours and that might be not necessarily a good thing, but if we're actually doing it, let's say, before we go to bed, that's going to really exacerbate the problem even further. 

So, it's not only what we do, also when we're doing it. That seems to be changing, and we're being exposed to light at nighttime when we shouldn't be and that's going to have an impact on cortisol and melatonin and things like that which is then going to affect our sleep. So, there's all that circadian stuff that's research that we've also need to consider. What are your thoughts about that?

Austin: Yeah, let's talk about that for a second because I think it's something we haven't addressed yet but I'm glad you brought it up, is that sleep is probably the single most important thing that a person can do to rapidly improve their brain function. Often people will say, "Oh, well it's the food, it's the exercise, it's the meditation." I say, "Mm, let's think about this." First of all, the things that we know are most helpful as it relates to food tend not to be the things people enjoy doing. Often it's cutting out the foods that they enjoy eating. So, right off the bat, that's going to be a challenge. When it comes to exercise, a lot of people don't love exercising. So, telling them, "Yeah, you can improve your brain function. Just get out there and go for a 45-minute run." Many people won't like doing that, and I don't know if you have much experience with this, but I can tell you that meditation is often nothing that relates to it being enjoyable. It is an exercise of the mind in its own right.

So, for the most part, what winds up happening is that health practitioners tell their patients, "Here is what you must do if you want to be healthy." It's all stuff that the person is going to hate doing because it is getting rid of the things that taste good. It is not sitting on the couch and watching Netflix, and it's getting up and going for a run, which many people don't want to do. It's being more mindful, which is not necessarily enjoyable. On the flip side, when I tell people, "Here's what I want you to do. Forget all the other stuff. Tonight, focus on getting seven to eight hours of good sleep." It is very rare, if not never, that people will tell me, “You know, I got a good night of sleep last night, and I wish I would have done something else. I'm not feeling better. I really wish that I would've had a worse night of sleep last night." It just isn't the case.

So, first of all, it's enjoyable, and second of all, perhaps equally, if not more important, is that getting good sleep correlates with better overall brain function. So, better sleep correlates with lower risk for Alzheimer's and depression, and basically every other brain condition. But over the course of just one night, getting good sleep can be the difference between eating healthy food and eating several hundred extra calories that come from unhealthy sources. When they do studies of people and sleep-deprive them for just one night, they show that people tend to preferentially gravitate towards and eat more unhealthy food. Similarly, what they show is that after one night of sleep deprivation, there is an increased emotional activation of the amygdala.

So, what we know then is that there are very real consequences as it relates to our health choices that come from sleep deprivation and that we can see changes in our brain function with as little as one night of not getting good sleep. So I think it is fundamental to prioritise sleep if we have any interest in brain health. To that end, as you said, there are so many things that we do wrong if our goal is to get good sleep, whether it's a light that we do or don't get, the caffeine, the alcohol, the timing of our meals, the way that we wind down at the end of the day, the temperature control. All of these variables go into the quality of our sleep, but often we're just doing whatever else is fun during the day, and then sleep is the afterthought. It's, "Well, I'm going to finish up these emails. I'm going to finish up this show, and then right into bed.” We don't give it nearly the credit it deserves.

Adrian: Agree 100%. I think that sleep really needs to be an integral part of any treatment for anybody. Like you mentioned, if you have a poor night's sleep, you wake up, you don't go for that run that you were going to go for because you're tired, you're lethargic, you start eating the unhealthy food, you're now more reactive to stresses that occur at work and it just leads that spiral downward. So, it's such an integral part, isn't it? And then we know from a physiological perspective what poor sleep can have on us in terms of inflammation, and neurotransmitters, and cortisol, and all those other factors that are going on too.

Austin: That's right. Every system that relates to brain function, whether it's our hormones, our immune system, our neurotransmitters, synaptic plasticity, it is all tethered to sleep, and all of them seem to do worse with not getting good sleep. Now, I will say there's one kind of interesting correlate or caveat to that which is that in certain populations, a night of sleep deprivation can improve mood. So, some subsets of people with mood issues, specifically depression, benefit from sleep deprivation. Interestingly enough, in short amounts, sleep deprivation, meaning skipping sleep for a night, can actually boost levels of a molecule called brain-derived neurotrophic factor. So, this gets to another kind of conversation around hormetic stressors and whether occasionally short doses of stressors may actually be helpful in jolting us out of unhealthy patterns.

Adrian: Yes.

Austin: But I definitely would say for most people most of the times my core message here is certainly not to skip sleep to try to take advantage of this. It's rather prioritise every night as much as you can getting in seven to eight hours because that is what is most consistently shown to correlate with better brain health.

Adrian: A hundred per cent. Okay, so you've mentioned obviously sleep. You've mentioned screen time, obviously mindful behaviours. Being mindful is obviously another important component and exercise. Now, from a dietary perspective, are there particular foods that people should eat that may be beneficial for brain health?

Austin: Yeah. I've spent a lot of time thinking about this and I, like you, live in an era where everyone has their diet of choice. So, it's vegan, it's paleo, it's keto, it's some low-carb, low-fat, low-protein, which some people would call fasting. Other people call it calorie restriction. Basically every permutation of the macronutrients and micronutrients that you can think of. I'll just start with my general take is that these types of diets, the more restrictive diets of which I would say a good example is the ketogenic diet, I think can be helpful for certain populations for a certain timeline of intervention.

But when I am talking about general brain health for the general population, I try to stick to what are the sustainable dietary choices that seem most correlated with good brain health over a lifespan. I think that is different from saying, "Well, I'm a person with a specific condition that needs a specific intervention." So, I just want to make that clear that there is no one diet that will work for everyone. But with that said, here are kind of my core tenets of what I believe is evidence-based as it relates to general brain health.

To that end, I think there are certain things that are most strongly correlated with good brain health as it relates to specific foods but generally speaking, I am a big proponent of the Mediterranean pattern diet. The reason for this is when you look at brain health outcomes, I tend to look at two major conditions because that's where a lot of the research has been done. Those are dementia, specifically Alzheimer's, which is the most common type of dementia, and depression because, from my perspective, the relationship between diet and mental health is strongest for depression, and it tends to be a condition for which there actually is some data as far as interventions in larger populations being efficacious. To that end, for both of those conditions, the overlap is the Mediterranean pattern diet. There's some other ones that people might have heard of like the MIND diet, but the overlap with mood, specifically depression and Alzheimer's, is Mediterranean.

So, what does that mean? First, I'll say this is actually what I try to eat most of, most of the time. Different people will slice the Mediterranean diet different ways, I believe, depending on their bias. So, some people slice it more animals, some people slice it more plant-based, some people slice it more whole grains. I think the truth is that there is no one Mediterranean pattern diet because the Mediterranean is a big area and people ate different foods and different ways over many different millennia.

But some of the core characteristics that I think stand the test of all of these people's opinions are, one, eating less processed foods. One of the most concerning trends that we've seen is that the global diet has moved towards a ultra processing of food. There's a huge difference between eating an apple and eating an apple pie. When foods are processed, meaning they have things stripped from them, things added to them, usually what we mean is removal of some of the core elements that relate to health, specifically to gut health, specifically dietary fibre. Usually, the add-ins tend to be things like sugar. So I think, again, the main thing would be avoidance of processed foods. As it relates to processed foods, I think the biggest things we need to look out for are the addition of added sugars, and in essence, the stripping away of fibre, such that when we eat a food, it converts readily into sugar. 

So, this mostly relates to carbs, I think, of the three macros that are worth paying attention to. I think that's the area that people can get the biggest bang for their buck. For most people, the easiest way to improve their diet is to cut out sugary beverages, because the correlation between sweetened beverages and worse health is the strongest of any as it relates to sugar and diet. People tend not to recognise that most beverages have added sugar and that all of these sodas and even fruit juices that we thought are so healthy are actually not and are correlated with worse overall health. So,again, lowering your intake of processed foods, be extra careful about added sugars, be extra careful about foods that tend to be heavily processed carbohydrate foods that break into sugar very quickly. But what types of carbs does the Mediterranean diet tend to focus on, well, here again, it's the whole grain less processed versions of that.

My take on that is that of the three macro groups as it relates to brain health, I think many people would benefit from doing a bit more personalisation. Some people can eat a big bowl of brown rice and not see a huge bump in their blood sugar. Many people cannot. So, I am increasingly interested in learning about how continuous glucose monitoring devices can be used to the benefit of people who are prediabetic or even pre-pre-diabetic. Long story short there, if you're going to eat carbs, try to eat minimally processed carbs, whole grains, trying things that are not conventional carbs. So, I like things like buckwheat, quinoa, rye, basically getting away from conventional wheat and rice is a good thing.

For the other macros, I think for fat, similar to what I said around the sugars, the processed versions of fats are those that have a lot of trans fats in them, which have been largely outlawed but you can still find in certain foods. But then the other area in which that processing gets us is oxidised fats. So, while we could say, for some reasons, that poly-unsaturated and monounsaturated fat are better for us or correlate stronger with brain function than do saturated fat, the downside there is, if you're consuming vegetable fats, things like corn oil and soybean oil, these tend to get oxidised. So, that's not good. 

On the flip side, some of the healthiest fats that I would say have been correlated with brain health and in line with the Mediterranean patterned diet would be olive oil, nuts, seeds, fatty fish, great source of omega-3 fats and then eggs, somewhat debated but I think just real quick as it relates to saturated fat, which many people would say it's the worst fat and it's terrible. I have not seen such strong correlations between saturated fat consumption and brain function. What I see is, if anything, it seems pretty neutral and ideally getting more of polyunsaturated, specifically omega-3 fats, has a benefit to brain function. 

Adrian: Terrific.

Austin: And then on the protein front, some of the protein sources that the Mediterranean diet would emphasise would be fish, nuts, seeds, eggs, pulses, legumes, poultry, and less red meat. Again, there's controversy around red meat for a number of reasons. I have not seen very consistent indicators that red meat consumption correlates with worse overall brain health, but I think in the aggregate, if you're trying to prioritise certain types of meat, the data would suggest that going more towards fatty fish and then maybe poultry as opposed to red meat as a primary protein source.

Adrian: That's great. Great advice and some dietary recommendations. And just quickly supplementation. Do you use supplementation, nutritional, herbal? Is there anything that you would recommend that might help brain function and reduce brain inflammation?

Austin: Well, my general take is I treat supplements as that. So, if I would take a supplement, it would be because I felt there was a nutritional deficiency. Where I think the evidence is maybe strongest here is, if you are somebody who is following a plant-based diet, especially if you're a vegan, B12 levels can be an issue. 

There are some other correlates to people who follow primarily a plant-based diet. The other big one in addition to some of the other micronutrients would be around omega-3s. I don't think it's controversial to say that most people don't get enough omega-3s in their diet. So, that'd be one in which I think that taking a high-quality omega-3 supplement would be high on my list of things to look at, especially if a person is not eating animal products. The most important omega-3s for the brain, as far as I can tell, are DHA and EPA. DHA is the more important structural omega-3 for the brain. For most vegans, for most of the time, you're just not going to make enough.

Adrian: Yeah.

Austin: So, I think that's important as it relates to brain function. And then some of the other areas I think are worth consideration are vitamin D. I mean, most people where I live seem to be relatively low in vitamin D levels. They may not have a deficiency, but they may have an insufficiency. So, I think taking a vitamin D supplement and also getting your levels tested is practical for many people. 

There's some other stuff that I'm learning more about, looking at certain components of the Mediterranean diet, so specific phytochemicals or phytonutrients called polyphenols. I think that's worthy of exploration. It's one of the reasons that I prioritise my coffee every morning, but there is some evidence suggesting that getting more polyphenols than what's present in diet would make sense for certain people.

And then another area where I'm focusing some time is understanding beyond omega-3s, some of their metabolites. So, specifically resolving mediators, both pro-resolving mediators and specialised pro-resolving mediators. It gets us really deep into a cascade of signalling, but the basic idea would be that, as we're looking at specific dietary nutrients that correlate with overall health and coming back to maybe this conversation around the immune system, we're now understanding that it may not be the omega-3 itself that is so powerful, but rather what it turns into that has a higher effect on resolving inflammation. So, there's some emerging research on these molecules, these resolving mediators that I'm following closely.

Adrian: Yeah, I think that's an interesting area, those SPMs and resolving mediators to help turn down inflammation when it needs to. So, that'd be an interesting area for research in the future for sure. 

All right. Well, look, I could keep going forever, I think. I'm mindful of time, but you've provided some really, really great information obviously about not just diets but also sleep and lifestyle-based factors that we need to consider to help improve brain function. I mean, ultimately the key is trying to make those changes early, but it's never too late to make those changes to help improve brain health. 

Austin: I appreciate that. If you don't mind, there's one more thing I'd like to address because I think that sometimes when I engage in these conversations, certainly there's some lifestyle factors that people might recommend changing, but we all know what needs to happen for us to be healthy these days. I just don't think there are many people out there who think it's a good idea to eat junk food. So, me saying “Junk food is bad for the body,” is not sufficient. Similarly, there aren't a lot of people out there. I mean, there are some who think that exercise is anything but good for the brain and for the body.

So, what I would like to just leave listeners with is, the implementation is absolutely critical. And how do we implement lifestyle changes? Well, one part is what I said before, which is go to the lowest hanging fruit, things that are going to be functional as far as changing our brains for the better and fun and enjoyable. To that end, I think sleep is an amazing first-stage intervention if you're trying to work with a patient on improved lifestyle compliance. So, maybe instead of saying “You have to go to a Mediterranean diet tomorrow,” you say, "Let's first work on something that we mutually agree is going to be beneficial and enjoyable," and that's sleep.

The other thing though is there is an absolute need, I believe, to focus on unconscious or automatic drivers of our behaviour into that. The main example would be habit formation. This is not something that I learned in medical school or residency, and yet we now understand that upward of 40% of the decisions, the actions we perform in a day, are driven by these unconscious processes which are called habits. So, if anyone's goal is to change somebody's behaviour, whether that's yourself or for your patient, and you're not using habit science, you're not getting that on board. Your best case scenario is you're only going to be able to work on 60 or so per cent of a person's decision in the course of the day.

So, I highly recommend to learn about how important habits are as it relates to how we make decisions in a given day, to understand how we can change our habits for the better, and the tools that are necessary to get us from A to B. It's usually not what people think. It isn't a willpower issue. It's not something we should blame people for. It's certain patterns of action that can either energise or deactivate habit loops that will enable us to offload a sizeable proportion of the decisions in our day to an automatic process. So, we're basically putting almost half of our brain's decisions into the hands of this automatic, unconscious process, and we have to choose whether we want to hand that off to somebody or a brain that we really feel great about that's going to make good choices for the brain, and it's going to constantly be pulling up into destructive action patterns. 

There's a lot of great books on habit formation. I've written several blogs on it. It's very basic stuff, but it has to be done in the right way to get the brain to pay attention. It isn't so basic as you're saying, "Well, willpower." It's actually not about that at all.

Adrian: Are there a couple of books that you can recommend?

Austin: Yeah, there are some that are pretty popular. I think Atomic Habits is probably the best example, that’s by James Clear. There's an author named Wendy Wood who is a California-based researcher, and she wrote a book called The Power of Habit, which is excellent. And then the last one I'd say is Tiny Habits by B. J. Fogg. He's another California-based researcher. 

All of these are great. I think that the goal is just to try one of these, and I mean consumers non-medical people get these books and it changes their life. But I think that, as practitioners, we have been largely unaware of how valuable these tactics are when we're able to implement them for patients. First of all, because people love to hear about them. Talk to somebody about this, they get excited. Assign them one of these books, they get excited. But then when you leverage it to improve healthy habits for medical benefit, that's just a whole new ballgame.

Adrian: Definitely. I mean, you make a really good point. I mean, certainly it's not just about providing information and education. We all know that what healthy lifestyle should comprise of, but ultimately it's about kind of behaviour change and it's a really great point.

Austin: And, sorry, I just wanted to clarify. The book by Wendy Wood is Good Habits, Bad Habits. The Power of Habit is by Charles Duhigg, an older book.

Adrian: Ah, okay.

Austin: They're both good though.

Adrian: All right, we'll certainly include links to those in the show notes for sure. 

Thank you very much for our discussion today. As I said, you've provided some really great information for practitioners for them to think about how they can help their patients improve brain function and brain health. I really like the fact that you're talking about making realistic changes for people and really being aware of the importance of habits and behaviour change, which are really an integral part. Certainly for me as a psychologist, I know that it's a really important component to working with our clients. We need to really consider how they make changes and help them with that process. So, thank you very much.

Austin: Totally. I would just say it's one thing to say you want to use them for patients. All of us are tempted to say, "Okay, I have this information, now it just goes directly to the clinic." All of us benefit from employing these things. If you're a practitioner and you're trying to do well by your patient, you're trying to do well in your relationships, you need this stuff more than anyone. 

If there's anything that I understood from my medical training, it was that we do not learn how to care for our brain. We do, in essence, everything that is opposite as far as it relates to our brain health. It's sleep deprivation. It's unhealthy food. It's sedentary behaviour. I think you got to put your own seatbelt on first, and this is a great example of it. So, you have to care for your own brain first, so then you're able to really leverage this to help others.

Adrian: Absolutely. So, thank you, everyone, for listening today. Don't forget that you can find all the show notes, transcripts, and other resources from today's episode on the FX Medicine website. I'm Dr Adrian Lopresti, and thanks for joining us. We'll see you next time.


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