Dhru Purohit Show - The New Science of Neuroinflammation and How to Protect Your Brain with Dr. Austin Perlmutter

Episode Date: September 15, 2022

This episode is brought to you by ButcherBox and Cozy Earth. Over 300 million people around the world experience depression. For the last half-century, the dominant explanation for depression has centered on serotonin. The basic idea is that low levels of brain serotonin or serotonin activity lead to symptoms of depression. But in the last several decades, a number of researchers have challenged the idea that serotonin plays a principal role, or even a major role, in depression. So, if it’s not a serotonin issue, what is it? Today on The Dhru Purohit Podcast, Dhru and Dr. Austin Perlmutter talk about why serotonin may not explain depression, but research on other brain pathways may provide answers such as neuroplasticity, our hormones, metabolic health, gut health, and the immune connection to the brain. They also discuss how there is a lot we can do through our lifestyle choices to help prevent and even manage depression. Dr. Perlmutter is a board-certified internal medicine physician and expert on how environmental influences affect our mental and brain health. He is a coauthor of the New York Times and international bestseller Brain Wash, which he wrote with his father Dr. David Perlmutter, and he hosts the Get The STUCK Out podcast. He currently serves as the Senior Director of Science and Clinical Innovation at Big Bold Health, where he is running an IRB-approved pilot trial exploring the effects of polyphenols on epigenetic expression. In this episode, we dive into:    -The top drivers of depression (1:42) -The connection between neuroinflammation and depression (9:30) -How our immune system influences our brain function (11:49) -What governs our brain state and how we make decisions (16:04) -The top causes of inflammation (17:31) -How exposure to particulate matter impacts our brain function (36:21) -The top foods for brain health (44:15)  -Why depression is not a serotonin issue (50:37) -Myths about serotonin (56:47)  -What you can do to improve your brain health (1:16:22) Also mentioned in this episode:   -Dr. Mark Hyman’s Himalayan Tartary Buckwheat Pancake Recipe For more on Dr. Perlmutter, follow him on Instagram @draustinperlmutter, Facebook @draustinnperlmutter, and through his website austinperlmutter.com.  This episode is brought to you by ButcherBox and Cozy Earth. ButcherBox has a variety of different boxes, and you can choose your box and frequency. For a limited time, you can sign up today and get 2lbs of ground beef free for a whole year by going to butcherbox.com/dhru. Cozy Earth are the most comfortable, temperature regulating, and nontoxic sheets on the market. Right now, get 40% off your Cozy Earth sheets. Just head over to cozyearth.com and use code DHRU. Hosted on Acast. See acast.com/privacy for more information. Learn more about your ad choices. Visit megaphone.fm/adchoices

300 million plus people around the world right now experiencing depression. The most important thing is there's a lot that we can do through our lifestyle choices to help positively improve our mood, potentially help prevent and even manage depression. Welcome to the Drew Proet podcast. Each week we explore the inner workings of the brain and the body with one of the brightest minds in wellness, medicine, and mindset. This week's guest is Dr. Austin Perlmutter. And today we're talking all things neuroinflammation. What are the the top drivers, especially lifestyle drivers, that cause inflammation not only in the body, but especially inside the brain? And also, what are the top things that we can do to get to the

root of neuroinflammation, starting with things, of course, diet, but a few other categories that Dr. Perlmutter prioritizes for the patients that he sees? A little bit about Dr. Perlmutter. He's a board-certified internal medicine physician and internationally, recognized expert on how environmental influences affect our mental and brain health. His research on lifestyle factors in depression have been featured and cited in peer-reviewed literature, and he educates on the topic on top podcast and keynote presentations around the world. He's a co-author of the New York Times and international best-selling book, Brainwash, which he wrote with his father, Dr. David Perlmutter, and in the book, he covers our poor

modern-day brain health and the role of everything. from diet to social media on our cognitive and mental state. We expand on all these topics and much more in today's interview. I hope you enjoy. Austin, welcome back to the podcast. It's a pleasure to have you here. I want to jump right in on our conversation today about depression. And, you know, there was a big study that came out.

We're going to chat about it in a second talking about how really, for the last more than a decade, really multiple decades now, this idea that depression is a serotonin, deficiency and it's all about a chemical imbalance is really just to speak plainly, kind of bullshit. So if it is bullshit, what are the top things that are actually drivers of depression, especially when we look from lifestyle medicine and a functional medicine perspective? Yeah, well, thanks for having me back, Drew. And depression, I want to be clear, is a real thing. It is a big deal.

We're talking 300 million plus people around the world. right now experiencing depression. But if it's not a serotonin issue, what is it? We need to talk about things like neuroplasticity, like our hormones, like our metabolic health, like our gut health, and especially the immune connection to the brain. Neuroinflammation, how our immune system is influencing our brain function. And what's maybe most important about this conversation is these are things we can do something about. It's really hard to know what increases serotonin in the brain. But it's a lot easier to do things that improve our gut. health, that improve our immune balance, that help promote healthy neuroplasticity.

So this is a reframe in the way that we look at one of the most disabling conditions on earth right now. And the most important thing is, there's a lot that we can do through our lifestyle choices to help positively improve our mood, potentially help prevent and even manage depression. You know, you've been so public, you've written on this topic, you've written books on this topic as well. Have you gotten pushback when you start talking about the fact that there are three? things that we can actively do. There's choices that we can make in our life to move us in the

direction towards health and away from depression. It seems to be a very sensitive subject. Can you talk about that? It is such a strange thing that in the modern world, we accept the fact that most of us in the United States will develop at least one chronic disease, will be put on a medication for decades of our lives. And there's nothing we can do about that other than wait for the moment where you're diagnosed and told, this is what the rest of your life looks like. And it's especially the case as it relates to mental health. I'm a doctor. I went through medical school, through residency. It was assumed that we had to look after our own mental health. And that's the state of training for doctors is the assumption that when it comes to mental

health, you're on your own until you get a diagnosis, in which case you can be prescribed in medication, like an SSRI, which works in maybe around two-thirds of people, causes side effects in around 40% of people and withdrawal effects in about 50% of people. That's the best we can do. And granted, psychotherapy can be very effective. But what we never talk about is preventive strategies for mental health. What is that? It's the idea that there are things that we can do not to wait until we develop depression, anxiety, or another mental health condition, but rather to promote good mental health now to help prevent those conditions from happening. And that just isn't a conversation that is really happening in the larger context of our medical discussions. So to your

question, the pushback piece, I think in general the medical system is set up to push back on anything that is an algorithm based. And these algorithms start with a diagnosis. They start with you walking into a provider's office and meeting the checkmarks or meeting that list of criteria that will enable you to have a diagnosis of high blood pressure, of diabetes, of depression. At that point, the algorithm begins. And you can say, based on your symptoms, based on your history, based on a number of other variables, here is the next step. It is to consider this drug. It is to consider this therapy. And really what we're trying to do here is push that back decades and say, what happens before you get to the doctor's office, before you have that diagnosis? And if you understand the pathways that are

driving our brain state that are driving conditions, risk for conditions like dementia, as well as conditions like depression, then you start to understand there's a lot we can do right now to help prevent our brains from getting to the point where we drop into that algorithm and the next step is medication. You know, you mentioned something, and I think that it's important to highlight this because this isn't just a topic about depression. And if somebody has depression, This is really the topic of protecting our brains and our bodies. And really, you know, this podcast used to be called Broken Brain. We talked a lot about brain health now.

Now we talk about a lot of different subjects. But a central message of the podcast then and now is what you do to your body, you do your brain. So help us understand that a little bit more. And I want to pull on this thread neuroinflammation. What is that? How is that linked to depression? but also, how is it not just about your brain health, it's also about your body health? I believe the single biggest thing we have missed in the conversation about health is the role

of brain health on everything that matters. And what do I mean by that? I think most of what we look at in health care is surrogates. So we look at high blood pressure and we say, we need to bring that down. Why? Why do we care? It's because that high blood pressure can lead to negative health outcomes that compromise our quality of life. If we say you have high blood sugar and we need to bring down that blood sugar, why is that? It's because high blood sugar over time increases risk for death, for disability, for amputation, for heart disease. But all of these things are still surrogates for what actually matters. And what matters is being able to enjoy life, having a health span, not just a lifespan. And our health span, our ability to show up, wake up in the morning and enjoy the

day is a direct reflection of our brain state, of our brain health. And if you ask what is going on in the brain, that is driving how we feel, how we act, how we think, it is these pathways that are being influenced by things like our food choices, our decision to exercise or not, whether we get out into nature, whether we take in a bunch of stressful media through our phones or decide maybe to meditate, our brain state is a reflection of what goes into our bodies. And so you alluded to this, there's been a real misconception that what happens in the brain is separate from what happens in our bodies. And what research is clearly shown is that is not the case. What happens in our bodies influences our brain function. And that happens through a variety of pathways.

For example, the gut brain connection, we're now understanding is a big deal that what happens in your gut influences your brain. At a basic level, of course it does. Your gut is where you get food. Food becomes the physical components of your brain. So of course your gut health is going to influence your brain health. But we also know that the vagus nerve, which is the longest cranial nerve, runs from the gut to the brain and vice versa. But the majority of the fibers run from down in the gut and through the rest of the body to the brain, not the other way around. So the brain is incredibly sensitive to what's going on in our bodies. And maybe the best example of why this is so important is the immune system.

Now, there are a lot of misconceptions about what the immune system does and what it doesn't do. For the last several years, and actually the last time we spoke, we talked about how people are looking at the immune system in the context of the pandemic. And really, there's a lot of fear, and there's a lot of ideas that you can boost immune health, and you can somehow fix your immune system by taking a little vitamin C. But it negates the understanding of what the immune system really is, because the immune system is not just a defense system against microbes. The immune system is a complex series of signals and cells that enables us to learn from the outside world and convey that signal to the inside of our bodies.

So let's take this one step further. Where is the immune system located? It's located in basically every organ system in your body, but the majority of your immune system, up to 70, 80% of your immune cells are based in your gut. And why is that the case? It's because they are preparing to learn from what happens in the outside world. They are sensitive to the food that you're eating. They are sensitive to the microbes in your gut. And they are conveying that data throughout your body and to your brain. So what happens in the gut influences your overall immune state,

and your overall immune state influences what happens in the brain. And there's one other point that I think is vital to make. It's that for a long time, and I would say leading up to this very moment, most people think that the immune system is located outside the brain. About 10 to 15% of your brain cells are immune cells. This is a totally different way of looking at brain health. Everyone likes to focus on neurons, so do I. They're fascinating.

They are the stars of the show. They have the star down on Hollywood Boulevard. But 50% of the cells in your brain are not neurons. They are glial cells. And one of those glial cells is an immune cell. It's called a microgleal cell. And this little cell, this tiny little cell, may be a principal determinant of our brain health, including our mental health. And it may be the receptor, the signal, the satellite dish that pulls in

the data from the other parts of your body and conveys it to your brain state, both responding to and instigating neuroinflammation. We can talk about what inflammation looks like in the brain, but really what we talk about is these microglial cells, these tiny little cells in the brain, are at the absolute center of the brain's inflammatory response and overall immune response. And there are things we can do to care for these cells, keep them healthy, keep them on our side. And for example, when we don't take care of them and we have poor habits, we're talking about depression, but there's a whole list of other chronic diseases that we're more likely to end up getting. What are some of those?

Right. Well, what I've tried to say in the past and what we've talked about a little bit on prior podcasts is that if your brain state isn't in a healthy place, you're basically at risk of everything. And that ranges from brain diseases, so dementia, Alzheimer's disease, other neurodegenerative diseases, to mood issues. And these are things that are a reflection of brain function. Mood disorders are a reflection of brain dysfunction. They don't exist somewhere in this esoteric mind. They are a reflection of how our brains operate. Same thing with dementias, which people feel more comfortable talking about as a disease of the brain. But if you consider what actually matters

as it relates to your risk for a disease, whether that's cardiovascular disease or diabetes or any range of the top diseases on earth. These have become these non-communicable diseases, right? These are, in theory, non-infectious diseases. So why would that relate to the immune system? Why would that relate to our brain health? If you understand that these diseases are a reflection of our decision-making, our choices, do we get up in the morning and go immediately? for our phones while we're eating some junk food, or do we get up, get some sunlight in our eyes, move our bodies a bit, maybe wait a little bit before we eat some food and eat some healthy food? Those choices are a principal determinant of our risk for all of these cardiometabolic conditions

that are the top contributors to death and disability around the world. And those choices are a reflection of our brain state. So what governs our brain state? Neuroinflammation, inflammation in the brain is being recognized to influence how we make decisions in addition to our mental health, in addition to our cognitive health, in addition to our memory. And so if you think about this, it means that if our brains are experiencing an imbalance in immune function, in this case neuroinflammation, it appears to bias us towards more impulsive choices, making it harder for us to make good choices around the food

we eat, whether or not we exercise, whether we give ourselves good sleep. So it is kind of the linchpin of this equation. It is what is your brain state today? And it seems to be a lot of to be the case that inflammation in the brain biases us towards a poor brain state, a more present focused brain state. This is based on the series of papers that have just been published in the last decade. One paper looked at people's inflammation in their bloodstream and asked, does this relate to their impulsivity? And the answer was yes. Another paper, they had people come in, healthy volunteers. They stressed them to increase inflammation in their bloodstream. What they found is when people had this increase in inflammation in their bloodstream, they made more impulsive choices. So,

From a real-time perspective, your inflammatory levels appear to bias your decision-making. And that is fundamental. Your biology is shaping your brain function. Your brain function is shaping your biology. But your brain function is shaping your quality of life, your decision-making, how you think, and certainly your mood. And just to bring it home on like a practical day-to-day level with habits, what are some examples of things that people do on a daily basis that are, items in their own life that are driving that level of inflammation up that could be leading to these impulsive choices which could be, you know, overeating, reaching for sugar, deciding not to

work out, you know, deciding to hang out with not the best, you know, people, whatever you would put in that category of choices. What are the habits that are examples of those? I think there are always going to be things that are slightly outside our control that are influencing our immune state. And that is the way that the world works. We may not always have access to the healthiest food. We may have stressful jobs that we can't give up. But when I think about what are the modifiable risk factors that seem like they're strongest in their correlation with inflammation and potentially neuroinflammation? I go with five S's. And so we're talking about stress. Stress has been strongly correlated with an overall inflammatory response. I don't tell people

just stop having stress, that's not practical, and it's not reasonable for me as a physician to tell people don't experience stress. Stress is necessary, but excessive stress for too long, damages brain function, damages decision-making, and appears to lead to neuroinflammation. So stress is one. Two is substances. We were talking about this a little bit before the podcast, but excessive alcohol use has been linked to neuroinflammation as well as overall brain decline. You can say similar things for certain types of illicit drugs, methamphetamines, and the like. But I think for most people, understanding that excessive alcohol use is a bad thing for your overall health, for your brain health, and may upregulate neuroinflammation. Can I pause you there for one second to do a little

sidebar? You know, there's always that thing about people just really trying to maybe understand for themselves what excessive looks like. It's a great question. Can we talk about that for a second? there was a study that came out. And then we'll come back to your list. Right. Yeah. So there was a study that came out in the last couple of years that showed that there was kind of a constant increase risk for brain deterioration that correlated with alcohol use. Often what you hear about is a U-shaped curve or an inverted U-shaped curve, depending on how you look at it with people who don't drink any alcohol and people who drink a lot of alcohol having the most issues with dementia and other brain-related conditions. And so this has been correlated with the idea of saying, oh, a glass of wine a day,

roughly a glass of wine a day, and maybe a little less if you're a female, may be beneficial to your overall health and to your brain health and to your cardiovascular health. I think the research here is a little bit challenging to interpret because there are so many confounders. We talk often about something like the Mediterranean pattern diet. And this is a diet that incorporates a lot of healthy fruits, vegetables, fish, is low in red meat, is low in processed food, and often incorporates something like a glass of wine on occasion. But the confounding variables here are, these are people who are integrated into community. Alcohol is often consumed in the context of community. And I think that's really important because just assuming that you need to go home and drink a

glass of wine because it's going to give you a brain benefit, I don't think makes much sense. And so the recommendation I've heard that I agree with is if you're not drinking already, you shouldn't start because you want the brain benefits. And to kind of answer your question more explicitly, when I was in med school, we talked about maybe two glasses of wine equivalent if you're a male per day is the upper limit and one per day if you're a female. I think what we're going to learn in the years to come is there may not be a safe level of alcohol consumption if you're really trying to preserve your brain function.

On the other hand, I don't think you can discount the value of alcohol as a way of bonding with other people because it's so embedded into the social fabric. If you are on a first date, it is an easy way to find some common ground to talk about. It is a social lubricant. And I'm not the person who's going to be out here saying, stop drinking. I had a glass of wine last night. It was delightful. But I do think moving forward, if we are looking for ways to optimize our brain function, we have to be cautious. And we have to understand that alcohol is a known carcinogen. it's a known neurotoxin, and it appears to increase neuroinflammation. So it's got to be a balance, right?

It's got to be an actual conversation as opposed to where we are right now, which is we don't have any issues with people saying, I went out and had several drinks with my friends last night, especially in the college years. This is 100% considered the social norm. And something we talked about a little earlier, but we can get into again, is that we have such a strong kind of prejudice against other molecules that are brain active. that may be far safer, but that don't come with a whole lot of these side effects that have been normalized as intoxication, hangover, feeling drunk. These are all things that, at least in

the social lexicona today, are considered well within the range of normal, acceptable, and healthy social behavior. That's not what the science would say. Right now, just like you and your personal life and just navigating the world and all, you know, talks and different things you do, are you drinking right now? Are you not drinking right now? I'm going through. phases, taking a couple weeks off, and then we'll enjoy a good bottle of wine or maybe a beer. I'm not ever going to be on this podcast and say, Drew, I've taken a hard line with this thing. It's just not really within my personality. I'm all about trying to find the balance perspective for the longest period possible. When I think about life, I think about area under the

curve. And so it's not a question of how healthy am I on a given day? It's how much am I enjoying life over the course of my lifespan. And so that means that any sort of very strong decision I make as to a black or white has to be very carefully considered. Similarly, to get back to this list as to things that relate to neuroinflammation, overall inflammation, sugar is a big one. And so that means both sugar in your bloodstream and sugar in your diet. These are things that are pretty strongly correlated with inflammatory markers. I would say of the dietary habits that I try to most strongly stick to. It's minimizing added sugar in my diet. Am I 100%? Absolutely not. But I'm probably 90, 95%. And I think that these are the scenarios where you say, you're going to do the best you can,

and you're going to make allowances for existing in the real world, interacting with other people. And if somebody has snuck some sugar into that salad dressing when you're at the airport and you don't really have a choice as to what to eat and you're starving, I'm not going to make a big deal about it. But I do think, coming back to the sugar connection, added sugar, is probably the single biggest toxin in our food supply right now. And it's present in 70% of the foods that you will find in the supermarket in the American grocery stores. And sugar, specifically sugar sweetened beverages are correlated pretty strongly with increased risk for dementia, as well as for depression. So these are things that are neurotoxic in a sense.

And it's partially because what happens with the connection between metabolic dysfunction and inflammation in our bodies and in our brains. So I think sugar is definitely a piece of this list that is super worth considering. And it's something that all of us can do better at. Yeah. And it's really those pharmacological doses of sugar that people are having on a regular basis. And on the flip side, you know, I know you're, you have worked with or advised levels as well. Yeah. And, you know, I'm an advisor with them as well.

And you've had Casey on the podcast. What's been great is for a lot of people, especially because inside of the app, you can get your metabolic labs. And a lot of people who even get regular lab work don't know they're fasting insulin level because their regular doctor isn't ordering it. So one thing that's been great for me is like seeing that, okay, having a lower or optimized fasting insulin level, I'm right around like, I think it's like 2.3, which is in the optimal category. Cool. Like I can have fun every so often and like have sugar as like a nice like my business part. always says like treat it like a recreational drug, right? Like you can have a little bit of sugar here and there and you're not worried about it and that's part of your metabolic flexibility. If you're

working out regularly, if you have a pretty dialed in diet, then you don't have to worry because I've seen people worry so much about sugar because they hear about the detrimental effects that can have in its body. And really we're just talking about the pharmacological dosages that a lot of people are having out there. And once you pull back from that and go more whole foods, then some sugar inside of your diet is not going to have the same type of impact because you have more of that flexibility. Yeah. I do think to pause to you for a second.

Please. You have a lot of guests on the podcast who have views that aren't mainstream as it relates to medicine. And I guess I'm one of those people. But this is a scenario where mainstream medicine and everyone else seems to agree that, with a couple of exceptions, I think back to an instance where my dad was on a national TV show, and they kind of pulled a quote from the sugar industry saying sugar is safe. What do you feel about that?

But for the most part, people agree that added sugar is bad for us. And that's conventional docs, that's integrative docs, functional docs. And when you look at what we're doing right now, World Health Organization suggests a couple percent of our calories per day should be sugar. We're eating 14 to 15 percent of our calories per day in added sugar in sugars that have been, you know, put into our foods. So this is a unique scenario where we can all agree that it's no good with the possible exception of people who are gearing up for Halloween candy. But yet despite that, we continue to do it. And so what we have is a scenario where the majority of

our foods, the majority of our beverages have sugar added to them. And it speaks to something that is fundamentally important, which is our brains, despite the fact that here we are in the 21st century, having a conversation through this amazing technology are based on systems that are millennia, if not millions, hundreds of thousands, at least years old. And one of those relates to sugar. As we've interacted with sugar in the past, it's been a ready source of added calories. It's been generally safe as far as the foods that are sweet tend to be those that we were able to tolerate. They weren't going to make us sick.

And so if you are a company that's putting together some new beverage, you're going to add something that is going to make people interested in purchasing it. And we've kind of just revved up that process to the point where it is the standard today, where sugar is added to almost everything. And it's almost not helpful to talk about the fact that sugar increases your risk of just about any major condition that we see as a top contributor to death and disability around the world, whether it's depression or heart disease or stroke or Alzheimer's dementia. That's kind of not enough.

What we need are the simple strategies to understand where, sugar is getting into our diet, and we need alternatives for that. And I do think, to your point, if you are aware, if you know what you're doing, if you're measuring your CGM-based glucose levels, and you can say, I ate this thing with added sugar, here's what it did, and here is my plan for it. That's one thing. But if you are just learning about this right now, I think where to start is the nutrition facts, the ingredient list. And the reason for that is that if you can start to understand that this metabolic toxin is being added to the food that you would assume is safe, I think it helps to build up a little bit of anger towards the fact that you are being poisoned

a little bit, at least as a starting point. And then you can pull back from it. But to start by understanding that if you are purchasing a processed food, a beverage, a snack, there's probably this metabolic toxin already included in it. That's a great place. And then it helps you to understand that if you are shopping for groceries, if you are shopping for food, unless you can identify the individual elements of what you're eating, you are by the probabilities, probably consuming high levels of sugar. That is for the people that I've spoken to, a major step forward and empowering them to have better health, because you've already started to break through the first barrier of understanding what goes into your body. And if you can get a CGM on you, I've really

enjoyed my time with the levels app. I think it's fantastic. then you can start to see in real time what it's doing to how you feel and what is doing to your blood sugar levels. But the first step I always tell people is just understand, first of all, it's in almost everything and then start to look for it in the foods that you're eating in a given day. Yeah. I wanted to mention one more thing about alcohol, and we'll go back to your list. I keep on interrupting you for these little sidebars.

I'm also, I just started a new training program. And as part of that training program in the gym, strain training program, you know, it's like, I'm you're strictly off of alcohol for for a period of time. And I also did like a big I turned 40 this year and I had like two weeks in Italy with my friends and family and other stuff. So we had a lot of wine. I was kind of whined out for a little while. So you know what? I am going to go like probably between now and the end of the year.

I'm going to just avoid alcohol. And just as like an experiment. I actually didn't really grow up really drinking that much. I grew up in a household that was pretty liberal with it. My parents were like here's the reasons why we don't drink. but you know, go for it if you want to, but just like be safe about it and here's this and here's that. So I never kind of got into it. It was never this forbidden fruit for me to like go off and desire. I took little sips here and there, but never was super into drinking. And then

I think that that whole idea of as you get older, how old are you by chance? At the moment, 33. 33. So I'm a little older than you, but you definitely start to notice those effects that are there. And though, even though I don't ever, you know, I probably drink to be a little bit tipsy, but I've never gotten like, you know, like full on like drunk or whatever. That sounds even funny to say for people who are probably listening. I just never had that experience.

But the impact and the hangovers, especially as you age and the contrast of you feeling so good. And you're kind of like, oh, do I, if I'm going to trade the chips in and because it's going to be with family or friends or whatever, I have to really feel like, okay, I know I'm not going to feel the. greatest tomorrow, but I'm going to trade these chips in for this moment of social. So it's a real

battle internally. I have no judgment on it and what other people decide to do, but that's just how I've seen myself evolve over the years. I totally agree. And it's also how I approach it. So you are a brain worker. You use your brain at a very high level in a given day. And because of that, you will be incredibly sensitive to when things are not optimized. I feel that it's the same for me. I spend my day thinking about stuff. And so I'm always doing little checks. How is my memory doing? How is my creativity doing?

Am I able to stay focused on a task? And what I do see is that even a little bit of alcohol will compromise my sleep and it will subsequently compromise my thinking the next day. Now, it might be subtle, but a couple of drinks in is significant. And so if you think about what a hangover is, and it sounds like maybe this hasn't been a big issue for you, but I've certainly experienced it. The next day, you feel pretty bad. and it's a lot of GI effects.

It's also a lot of cognitive effects. You might have a headache, but your thinking is off. What that is in reality is a buildup of toxins. You know, this is the breakdown product of that alcohol, as well as things like dehydration and other poor decisions that a person may have made when they were intoxicated. But that is an actual affront to your brain health, right? This is definitely not good for your neurons.

It's definitely not good for your glial cells. And I think if you're putting all the chips on the table, there may be instances a wetting, a best friend's birthday that absolutely you want to go out. You want to celebrate. You want to enjoy a couple of glasses of wine. Where I think we get into issues is just like with diet. You know, there are instances where you want to have that slice of birthday cake and I say, go for it. However, when that becomes a daily occurrence, we're talking again about area under the curve. We're not talking about a specific outlier. As it relates to health span,

that's the conversation I believe we need to be having. And if you start talking about weeks, and months and years of dietary patterns that include a good amount of alcohol, that's not trivial. Just like it would be the case that you'd say, one day I ate an unhealthy meal, not a big deal, right? The big deal is if that's your dietary pattern. And to bring this back to the conversation about depression, what the research would indicate is most consistent is that it's not a question of, did you eat a little bit of a certain food, right? Did you exercise a couple of days that one week. What matters is our patterns over time. So it's a Mediterranean pattern of diet over years that seems like it's the best indication for something that may help prevent and even manage depression.

It's not saying, I ate a handful of blueberries today, so I'm healthy. I can go have a bottle of wine. Or I had some fresh vegetables. I suffered through that kale salad. So now I can go sit on my couch for the rest of the day and watch an entire season of whatever on Netflix. It's a question of How do you set yourself up for the habits that will last you for a lifetime that over time are going to be most advantageous to brain function? So these decisions that we make as far as do I want to leverage tomorrow's brain function for enjoying the present moment a little bit are important primarily as they represent trends. And that's where things can potentially get derailed. I see this especially the case with people who are coming out of New Year's resolutions. and they were supposed to be going to the gym, but instead they do something else.

There are these window periods, these critical periods where we can create new habits, where things get changed up in life. And I think these are instances where we tend to fail because we set ourselves up for, I'm going to do this 100% for five days, and then we drop off. So another kind of correlate to the conversation that we're having is, the more you understand your brain function, how it responds to, how it programs in new information, the less you're going to be subject to and kind of biased by prevailing trends in the world. The more you're going to be able to direct your brain health.

And I do strongly believe that the ability to direct the health of your brain is one of the single most important variables as it relates to our long-term health, as it relates to our long-term happiness in life. Well said. So let's go back to this list. You were talking about alcohol. You talked about sugar. What do you want to go into next? Another variable that I think is it's becoming a bigger deal relates to smoke. And you probably had no idea I was going to say that.

I mean, I actually was going to ask you about this. Really? Yeah, because there was a study that came out recently. But continue, I don't want to steal your thunder. Well, similar to when I talked about sugar, it's not just the sugar in our diet, but the sugar in our bloodstreams that we want to worry about. When it comes to smoke, it's the smoke that we may consume via smoking cigarettes, which, again, like sugar is objectively bad. There is no one out there talking about cigarette smoking is something we should endorse or that's something that is good for our health. So it's almost a non-starter.

If you are a smoker, it is worth understanding that this may be one of the single most important things that you could do to improve your brain health is to stop smoking. So I do think that's important. But the bigger problem in my opinion is what we're seeing now with exposure to particulate matter, specifically PM2.5. These are small little particles that are in smoke. So whether it's wildfire smoke or just air pollution. There's a lot of research that's come out in the last decade that correlates exposure to these fine particulates and our risk for conditions like dementia. So let's start there. The smoke that gets into our lungs, specifically these tiny little particles, seems to correlate with risk for diseases. Heart disease is a big one. Respiratory disease is a big one.

And what we're now realizing is one of the pathways connecting all of these seemingly diverse pathologies is inflammation, that these little particles when they get through our lungs and into our bloodstream seem to induce inflammation. Yeah, and just so everybody's, you know, who's following along, obviously it's very clear when you have like a forest fire or whatever. You can see the air is smoky, but in a lot of places, especially indoor air, even if the air looks clear, it can be filled with particulates, these small particulates that can penetrate your body, can cross the blood brain barrier, and as you mentioned, can lead to inflammation inside. Yeah, it's accurate.

And there's some absolutely fascinating research that's come out in the last few years showing that exposure to air pollution is correlated with more violent behavior. And they've done mapping studies where they've looked at air pollution over large populations, millions of people. And then they correlate that air pollution with rates of crime. What they found is not overall crime as an issue, but violent crime, meaning people commit more violent crimes when they are exposed to more air pollution. There's other research that looks at children's cognitive function as a reflection of the air quality in their school district.

And they've shown that children's cognitive function declines as a function of increased air pollution. And so when you combine that with the bigger studies that show that conditions like Alzheimer's may increase when we have more exposure to air pollution, what I think we can say pretty clearly is that air pollution is a brain toxin. And what we're now understanding about this is that one of the principal pathways by which the air we breathe modifies our brain function is through the brain's immune system.

In cell studies, they've shown that these small particulate that are in the air influence our microgleo cells, that they can polarize them or basically direct them towards a more inflammatory state. So this is really important for a lot of reasons. But one of them comes back to one of the points that we discussed earlier, which is this misunderstanding. understanding that what happens in the body and what happens in the brain are somehow separate. If the air we breathe is affecting our brain function, is affecting our thoughts, our mood, is affecting our risk for dementia, then certainly everything that comes in through our skin, everything that comes in through our gut, and also what comes in through our eyes and our ears is modifying our brain state. And it, in essence, dissolves this myth that the brain is separate, that it's in

its own little locked box. Sure, it's in the skull. Sure, there's a blood-brain barrier. But your brain is obviously responding to what is happening in the outside world. And we get to a little bit of philosophy here or just kind of how you see life. But if consciousness is driven by biological variables, is influenced by biological variables, which it is, the way that we experience and feel life is a reflection of our biology, then we can significantly influence our overall trajectory of our conscious experience of life by modifying. those variables that come into our brains. And it means we're not locked into thinking in a certain way, feeling a certain way, that that is a dynamic reflection of what we're putting into our bodies. So to me, that unlocks the significance of things like diet for depression. Because now all of a sudden, it's not your brain experiences depression. There's nothing you can do. It's your brain is constantly

responding to the environment, responding to the inflammatory signals, responding to the hormones. and we can modify those things through our food. So it opens, I believe, a very significant door moving forward with mental health issues being one of the biggest problems on Earth today. I'd actually argue the biggest problem because coming back to my initial point, quality of life is what matters, right? It's not heart attacks. Heart attacks matter a lot because they take away quality of life.

It's not cancer. Cancer matters a ton, but it matters because it takes away quality of life. And so to jump ahead and say, how do we optimize mental health? It's optimizing brain health. And how do we do that? It's modifying the inputs coming into our bodies, the foods that we eat, our state of gut health, the hormones, the neurotransmitters for sure, and certainly our immune state, which is something that we know we can change based on what we put into our bodies. Yeah. One thing I wanted to mention about the air is that often we think of it as the air outside, and that does play a role. But, you know, for a lot of people, the easiest hack is to when you can, your indoor air is actually often way more polluted than the outdoor air, like off gassing, other stuff, especially like we just built this studio. There's a ton of new furniture. There's low VOC paint and, you know, the healthiest paint that we could find, but it's still

pollutants that are inside of the air. Unfortunately, in the building that we're in right now, there's no window that we open in this corporate office, but we've had like air filters, you know, run. But again, you don't have to go get a fancy air filter, just even, letting in fresh air inside your home, especially during the day and working. Freakonomics did a whole two-part series on air pollution and how it impacts the economy. And they highlighted a study of also how you were talking about bad decision and kids. They highlighted this one study where they found that umpires in Major League Baseball on the days that air pollution was highest in these outdoor stadiums. how the decision making went down significantly in their ability to call a strike a proper strike

or you know a ball or whatever else was there and i think the thing is zooming out it can all feel a little bit overwhelming like okay now we got to think about food we got to think about air we got to think about this but to me i always feel it's better to be aware of these things and then to find the simple low-cost hacks rather than be a victim and not know that these things are influencing you for the worse and leading to all sorts of issues down the line. Any thoughts or comments on that? I agree with you. And I would say you need to know the playing field to play. And that's what we're talking about here is what are the variables that are influencing your brain function in a given day. And I also think everything we've talked about for the most part

is modifiable. And you don't have to fix them all at once. And you don't even have to fix them all. These are all opportunities. They're keys for these locks that can help us to empower better brain health. I do focus a lot on diet. I think that as it relates to the inputs going to the brain, certainly the eyes and ears, so paying attention to the stressful media you consume, paying attention to the conversations you're having with people, people tend not to realize that what you consume through your eyes and ears is influencing your brain state directly. But as it relates to diet, I think it has to be simple, at least as a starting point. And so when I look at the research around brain health, both dementia risk and depression risk and the diets that people are eating,

it really centers around some very basic tenets. And those tend to be those that are represented in the Mediterranean-style diet. And so, again, we mentioned the Mediterranean pattern diet. It's one that is low in ultra-processed foods. And I know your partner, Mark Hyman, talks about this a lot. Ultra-process foods are a huge problem because they've stripped away a lot of the nutrients and added in a lot of the junk that no one needs to be eating. But Mediterranean diet is one that is low in processed foods. So you're eating a vegetable as opposed to a processed vegetable dip. You are eating a piece of salmon as opposed to some sort of a salmon spread

or opposed to some sort of processed food that you got in the middle aisles of the grocery store. But when you look at the nutrients within the Mediterranean pattern diet that seem to be most strongly correlated with positive health outcomes, comes ranging from mental health to dementia to cardiovascular health, etc. You look at these categories of nutrients that are in food. And many people know there are macronutrients. So your fats, your carbs, your proteins, that's all important. Many people know you have micronutrients, and that's vitamins and minerals. We know that minerals and vitamins are very important to our overall health. They're necessary for our brain health. Talk about things like vitamin B and magnesium.

These seem to be correlated with our overall and as well as our brain health. And then you have phytonutrients. And that's an area that I'm actually investigating right now in a clinical trial because there are 8,000 plus phytonutrients that have been found in plants. These are, in essence, molecules that plants produce to help defend them against their environments. If somebody in the other room was sick, you could move away from that person. If there was a polluted river, you could leave that river. but for a plant, you're kind of stuck.

You can't just pack up and move. So plants produce these anti-stress nutrients called phytonutrients, of which the best example is polyphenols. People may have heard of polyphenols. And so a diet, like a Mediterranean diet, tends to be very rich in polyphenols. And it's actually pretty consistent with what we see in other blue zones. It's prioritizing polyphenols, phytonutrients.

These are found in colorful foods. So colorful plants, cruciferous vegetables, dark leafy greens. They're also found in high concentrations in coffee, as well as to some extent in a drink like wine. People will talk about wine as a benefit because, oh, you have these polyphenols, you have these nutrients, which are antioxidants, but relative to the downside to alcohol, I don't think that should really be a part of the equation. But tea and coffee for sure, spices, herbs. These are highly concentrated forms of polyphenols.

And again, polyphenols have been linked to overall better health. people who eat more polyphenols, lower rates of depression, dementia. So I think that's an area where people can say, how am I going to promote overall brain health over the lifespan? Choose foods, rich in polyphenols. That's colorful fruits and vegetables. That's spices. That's coffee.

That's tea. There's some unique plants, one that we're both aware of Himalayan Tardy, buckwheat, which is a non-grain seed that is especially high in nutrients like quercidin, rootin, luteolin. These are polyphenols that have been linked to. overall health. One of the reasons for that is because this plant just deals with stress really well, so it has to create these high levels. But polyphenols as a group, I think, is important. The other ones I would describe would be omega-3s. So there's been a lot of literature connecting omega-3 intake. I know

something you've spoken about with brain health. There's a lot of kind of complex science around that, but at a very basic level, your brain is mostly fat when you take out the water. The quality of that fat seems to matter for the quality of brain function. Omega-3s seem to be one of the most important and represented fats in the brain. So you want to have maybe switch out some of the unhealthy fats and put in some healthy omegas. Those come from diet. You can't get them really in high levels through anything else because they're essential. And then omega-3 is also influenced immune function. They influence a number of other pathways. So there's a lot of conversation about omega-3 intake and lowering overall inflammation in addition to lowering neuro-inflammation.

And then the last kind of group there, which I think is relevant, is pre-in probiotics as it relates to overall health, brain health. And that really comes down to this connection between the gut and the brain, this bidirectional connection by which what we eat and the state of our microbiome, the state of our gut health, is influencing our brain state. And so it's still early in the literature as it relates to are there specific bacteria that we should consume that are going to improve our brain health. There's a couple of small studies with a couple of strains of bacteria. But what does seem to be the case is that the overall state of the gut microbiome and our gut health does relate to our brain health. And at a very basic level here, we can promote overall gut health by

prioritizing fiber in our diets, by consuming fermented foods, which are a good source of healthy bacteria. And coming back to that first point, polyphenols, which are these plant nutrients, have now been shown to positively modulate our gut microbiome. So that's kind of where I would go, these three pillars as it relates to how from a dietary perspective, we can help modulate our brain state, in addition to the variables I already described, which are paying attention to what comes in through your eyes and ears. These are low-hanging fruit. Every day we can be asking, what am I taking in that is unnecessary that may be biasing my brain towards a negative state, whether it's the food we eat, the news we consume, the social media we consume, the conversations

we're having with other people. And if you can start making just a small improvement in the quality of those variables, I think it makes a big overall improvement across the lifespan, across our health span, and across the kind of continuum of what our brain function represents over the decades of our lives. I want to come back. You know, when we first started and opened up this interview, we were chatting a little about that study that made a lot of headlines recently, and I believe it was in the journal,

Nature's Molecular Psychiatry. Yeah. Yeah, and I think it would be useful for our audience to just touch on it a little bit. And everything that we've been talking about today has been built on top of that and really talking about root cause medicine and what the real drivers of things like neuroinflammation and depression are more likelier to be. But just, I think it's worthwhile chatting. What do they talk about in that study and why did it make such a big splash? Right. Well, talking about depression, as you brought up before, depression has been, depression has been.

kind of pinned on this neurotransmitter serotonin. That was the donkey the tail got pinned on, and it stayed there for the last 50 years. With the subtext of part of that being that there's a chemical imbalance, we're not sure why that's happening, but it's there, and that the way to solve it is through medication. That is a clear description of this closed circuit loop. It is that if you are a person who is experiencing depression, and we should clarify here, this is clinical depression where you're diagnosed by a health practitioner, not just I'm feeling low today,

that the dominant explanation for what's going on if somebody said, what is happening in my brain would be there's an issue with your neurotransmitters and especially serotonin. The idea being there's less available serotonin and the serotonin that is available isn't doing its job in the way we would want. And so if you believe that, then the next step would be to say, what can we do to improve your brain's serotonin function? And the solution to that would be to use a drug, in this case something like an SSRI, a selective serotonin re-uptake inhibitor, that increases serotonin levels in the brain. And if it was a serotonin problem, and if this drug increased serotonin levels, then we would expect for people to be healed for their depression to go away. That in a nutshell is the basic of kind of pharmacotherapy for depression with the majority of antidepressants being based around neurotransmitters.

So whether it's an SSRI, an SNRI, a TCA, even an MAOI, these are the most commonly prescribed antidepressant drugs. They're supposed to work by increasing levels or changing levels of receptors for neurotransmitters and levels of neurotransmitters. So that's the context. That's the dominant way that we've looked at depression for the last couple of decades. Before this study came out, which again, created waves. A lot of people were talking about the fact that this doesn't make sense.

And why is that the case? Well, if you look at animal studies or cell studies, if you treat neurons with a SSRI, serotonin levels go up right away. We're talking hours, right? It takes weeks for many people to see an effect from SSRIs. So that doesn't really make sense. And then coming back to how many people actually get a treatment response. If you go with the optimistic projections, two-thirds of people or so will get a significant treatment response from an SSRI.

There's been a number of studies that have questioned whether the majority of the effects of SSRIs are actually placebo-based. And that's really interesting. But the bottom line to this is SSRIs are in no way a perfect drug as it relates to reversing depression. Then the other piece that we spoke about before is side effects, withdrawal effects are huge. So we're talking 40% of people at least with things like sexual side effects, GI side effects. We're talking 50% of people with really high rates of significant withdrawal effects. So not a clean drug and maybe not a great effective drug compared to some other drugs that exist on the market. So this has led people to say maybe it isn't just serotonin and explore other hypotheses.

With that said, it's always been one study here, one study here, one expert saying this, another expert saying this, questioning it. But last month, I guess depending on when you're listening to this, in July of 2022, this paper came out, which was a review of all the reviews. And it looked at, it's called an umbrella review. So it looks at all these meta-analyses and other studies to ask, is there a real signal here? is there a substantial connection between serotonin levels, serotonin activation in the brain, and depression? So they looked at a bunch of different studies. They looked at serotonin metabolites in the bloodstream. So to basically say, if it's increasing serotonin, we should see an increase in this metabolite.

They didn't see the connection there. They looked at receptors in the brain for serotonin and said, if this is working, then we should see changes in the serotonin receptor. They didn't see that there. And they sequentially went through each of these different ways of. approaching this question, which was, does serotonin issue or do serotonin issues explain depression? And the conclusion was basically no, that the connection doesn't exist in the way that we thought. And there are a number of reasons why this created all of these waves. One is, if you challenge the dominant theory of a condition, whatever that might be,

that's going to shake up the way that we look at it, right? And so SSRIs are among the most commonly prescribed drugs on Earth, and they're the top drug that is being used to manage depression. And if it isn't a serotonin issue, then does that make sense? There's some caveats to that, but that was one of the big questions that's been asked. The other piece was, if it isn't a serotonin issue, what is it? What's going wrong? And so we've talked about some of those other hypotheses, whether it's neuroinflammation or issues with the HPA-access stress pathways or issues with brain metabolism, glucose, insulin. But what I think is so great about this is it forces us to become curious again. It takes away

that black and white idea of we have the solution. It's this drug because this is the issue with it. And it necessitates a reevaluation of what we can do to reverse, to prevent, to manage depression. So it takes us right back to where we were, which is saying we need to ask what in our bodies is influencing our brain function. That's our food. That's our gut health. That's the state of the hormones in our body and in our brains. And these are things that we have levers for. One of the things that I brought up in a recent article is we have this, I think, misconception that if it's a serotonin issue in the brain, that we can modify that based on whatever we decide to do.

So people will say, oh, well, I'll just take a serotonin supplement. There's very little evidence that that does anything. And why is that? Because serotonin in your gut does not get to your brain. It's a nice idea. You know, people say the majority of your serotonin your body is in your gut. That's true, but it doesn't mean anything for your brain. Your blood brain barrier will not allow that serotonin in. Then you take it a step back and say, well, what turns into serotonin? It's

tryptophan. So I'll just eat a bunch of triptophan in my diet. Well, that's a nice idea, but the transporter for tryptophan is much more receptive to every other amino acid. So tryptophan's kind of the last one led into the party. So there's not a lot of evidence that eating a big triptophan meal that Thanksgiving turkey is actually going to influence your brain's serotonin levels. It's unclear that anything we do from a lifestyle perspective is really positively influencing our serotonin level. So you could kind of close the loop there and say, well, what's the point? And that's why the other stuff is more important. That's why we need to be paying attention to food because food influences our inflammation. If you really want to stick on

serotonin, a little bit of trivia here, your brain's conversion of tryptophan into serotonin will significantly change based on your levels of brain inflammation. If inflammation is present in the brain, tryptophan gets shunted away from serotonin production and towards another pathway that can have either neuroprotective or neurotoxic effects. So it all kind of comes together. And what I'd advocate for is let's just all be humble about this and say we don't really know yet. But what we do know is that it's more complicated than we thought. What we should know is that there's more we can do than what we thought. and let's focus on things like nutritional interventions that are more widely accessible to people than are these drugs that may not work for everyone and have all these side effects.

You know, what's interesting about this paper, and thank you for so eloquently breaking it down and, you know, taking our audience on that journey is that I was, when we were chit-chatting before we started recording, I was telling you that a couple months ago, a few months ago, I had on a gentleman, a journalist, Robert Whitaker, who wrote a book called Anatomy of an Epidemic, which is kind of one of the go-to books that a lot of integrative, functional, and just even open-minded psychiatrist, they kind of pass it around like it's like this secret thing because for a long time they were afraid to share that this was a book that they read because it was considered blasphemous, the content and the material.

It's no different. It's not highlighting anything too different in these studies, except it's more of a journalistic approach. And in that book and in his work, Robert Whitaker, who was on our podcast, was saying, you know, because I covered. And when SSRIs first came out, I don't know what year it was. But I believe he was talking about he was writing this piece for one of the newspapers in Boston. He's like, I went to the scientists to talk about like how groundbreaking this is. Like we found the thing that fixes depression. We're never going to have an issue with it before.

and I was asking them in pulling the thread, the first few articles were super complimentary and just highlighting this innovation. Then I started writing more thoughtful pieces. Well, how does actually work? And I was talking to the original scientist, again, I don't remember what university, but he talked about it in our episode, who came up with this idea of a chemical imbalance. And I asked him, well, it actually, there isn't a chemical imbalance that this is solving. And that's not why these things work. And they were the first people to say that, Yes, I know, but it was just an easy way for the, you know, public to understand it. So we didn't go out there and correct it.

And there's that, but it's also the drug companies ran with that story. Yeah. Because it was just an easy thing to do. And so much of our advertising and pharmaceutical advertising took advantage of that, right? Are you feeling low? Are you feeling this? Are you feeling that? You know, it might be due to a chemical imbalance, you know, this blah, blah, blah, blah, blah.

And the interesting aspect of it, this was a full circle. often on these podcasts, we've had experts come on and talk about how what we know and actually can prove in the literature, it can take years. I think it's like 17 years on average before mainstream medicine it catches up. This was a perfect example of many people responded very negatively to that podcast that came out with this journalist Robert Whitaker. And I got a little bit of blowback on it on YouTube and different things like that. And this study came out eloquently and, you know, peer reviewed and everything like that. And we need both. We need both aspects of it.

And all of a sudden there was a lot more open-mindedness of, okay, yeah, maybe this isn't the full story. And the last thing I was mentioned is the other thing I really appreciated about, I started following one of the lead authors of the study, a woman from the UK. I believe that, you know, I forgot her name, but we'll link to it in the show notes. it was really interesting to see them also on this Twitter thread. She was like, well, what does this bring up? And she mentioned, I believe, you know, we have to start looking down the direction of like neuroinflammation and what does that do with like depression? So, you know, I don't know what point I was trying to make with that other than just

this is society growing up and medicine growing up and us realizing that often the idea that our ills are caused by one single thing is the exact cause of our problems. It's not usually the case. and we are now kind of becoming more sophisticated as a society and understanding that. That's right. One of the things I really appreciate about your podcasts and the conversations that I've heard you have is that, you know, the world right now especially is it wants black and white. It wants to be told this is the solution. You have this problem. Here's the solution to it. And I think as we can recognize, the world is gray. It's shades of gray. I mean,

hopefully not 50 shades of gray, but there's shades of gray. And that's the reality in which we inhabit. And so to move away from the idea that we had depression solved on lock, which was never the case. Let me just give you an example. So in the clinic that I did my residency training in, I would have a person come in who said, I've been suffering from depression for decades. I've never figured out what it was. I had this when I was younger. And they've been on an antidepressant for decades, but they had a strong family history of depression. They had a number of other illnesses and they never really figured out exactly what it was, but this medication was working for them. That person would be managed with the same drug that I might prescribe for somebody who came

in and said, you know, my spouse just died and I've been for the last couple of months feeling really low about that. And that might be the same drug that I would give somebody, in theory, who came in with the flu and was feeling really, really sad. So the point being here, I think that as it relates to our brain function, we're still so naive in the assumption that we understand exactly what's going on. And that so many things can manifest as a term like depression. We know from the literature that when people have an inflammatory reaction in their body, whether because they were injected with a piece of bacteria that induces inflammation called LPS, or because they're sick, they got the flu. people feel social withdrawal, people feel low mood, people feel low energy. They experience depression as a reflection of the inflammation, the infection going on in their body.

But if you lose a loved one, you might also feel really low. You might also feel low energy. And it's, I think, crazy to think that it's the exact same pathway, that in both cases, it's just, oh, your serotonin levels drop. We don't have evidence for that. And I think in many ways it'll be like the way we look at nutrition or the way we had looked at nutrition. We assume, oh, well, it's a calories in, calories out thing. Done. Story's solved, right? All you need to do is eat less. We've seen that doesn't play out, right? And we talked

earlier about glucose. Glucose from one food is different from glucose from another food. Your levels of insulin, your levels of fructose, your levels of uric acid, your levels of inflammation as a reflection of metabolic function, your adipose tissue stores, whether they're white or brown adipose tissue, all of these things influence our overall weight, influence our overall metabolic health, it's nuanced. And when it comes to the brain, it's even more nuanced. How you experience life right now, how we converse is a reflection of trillions of synapses, billions of neurons. And so it is a nice idea to think that we have solved for depression by identifying a single neurotransmitter. You know, it's funny, in ancient Greece, we're talking 3,000 years ago.

They had a term called melancholia. That was their version of what we would call depression. now. And they felt that what was most beneficial for this condition was exercise and calorie restriction. Neither of those speaks about serotonin. And yet what we now understand from the literature is those are two powerful interventions for our health. We know that exercise liberates a molecule called brain-derived neurotrophic factor, which enhances our brain health, which may protect us against dementia, which may protect us against depression. We know that calorie restriction, or at least having longer windows between our meals is a powerful way to improve our metabolic health, which, as we've discussed, is one of the pathways that is involved with our overall brain function.

So the point being, at least they were curious, had different ideas on the table. We think with all of our advanced medicine, now we have the solutions. And we do have some. I'll be clear on that. We do have some solutions. But I think we're still away from understanding depression. And the last point I'll just say on that is what we know about depression, personalization is still in its infancy. But what we can say is that based on a person's individual patterns of, let's say, family history, they may be more responsive to one SSRI or another. So that's a common theme. If they have a family history of depression and certain SSRIs work well, we might consider there's a genetic variant that responds better to an SSRI. But similarly,

what we're learning is, if people have higher levels of inflammation in their bloodstream, they may be less responsive to certain antidepressants and more responsive to others. For example, ketamine. That speaks to a level of personalization that assumes there's more going on than a single neurotransmitter imbalance. And I think that's where we have to go next. So you can go to the larger conversation about what is everything on the table as it relates to depression.

It's not just the conventional pharmaceuticals. It's ketamine and other psychedelics. It's transcranial magnetic stimulation. it's ECT. These are all different modalities that probably all work in a slightly different way. And I will just say something that I found very interesting is SSRIs act on neuroplasticity. SSRIs act on neuroinflammatory pathways. So if there is a benefit to SSRIs, it may be completely uncoupled from serotonin. It may be because they increase levels of BDNF.

So it doesn't mean we need to throw the baby out with the bathwater here. and I'm not suggesting that SSRIs are a worthless drug, but I am suggesting is we all need to take on a little bit of curiosity. Depression remains one of the biggest issues on Earth despite the use of our conventional antidepressants. Why not be curious? And that means looking at everything from conventional drugs to psychedelics as possibilities to address what I believe is the biggest crisis of our day,

which is poor states of brain health. You use the word curiosity. I think it's a, is it Mark Twain quote? It's hard to have a man. Everything's a Mark Twain quote. Everything is, that's another meme that's out there, right? It all comes back to Mark Twain or Abraham Lincoln or somebody like that. But there was, what's that quote?

It's hard to get a man to be curious about something when his salary depends him not. Is that actually Mark Twain? Can somebody Google that? I think Mark Twain actually tweeted about it. I'm not mistaken. Well, we'll figure out who said that. But the part and the reason that I mentioned that, whoever, that's attributed to is that I think it's also okay to have a conversation of there are some people

that don't want us actively exploring those, not for any other, you know, grand conspiracy other than just financials. Financials are a strong motivator to shut the conversation down. And I think that that can come from special interests, that can come from any industry, right? Pharmaceutical industry, other industries that are there, there can be reasons why. And this idea that things are either, we saw this a lot during the pandemic, that the science is settled or consensus science, you know, that is often used as an approach to get people not to explore things. Another area that you are also, you know, have a deep expertise on, which is completely

upended. We probably have to bring you back for another episode just on this, is the whole idea of amyloid plaque and the recent study that came out about the forgery that happened in the discovery of how amyloid plaque was a central aspect of what leads to Alzheimer's and how using Photoshop, a tool that a lot of people are familiar with, the results of were intensified that amyloid plaque was given more favoritism as being the central pathway. For those that are not familiar, you know, we'll link to a couple articles and other things like that inside the show notes. But what's tough and what's important for people to understand about the scientific

method is that sometimes when things have so much inertia behind them and the right group and NIH funding and sometimes that could be conflicts of interest, there's not funding and incentives to question that. Nobody wants to go and do a study on, hey, is this thing that? that somebody just said was the way that something happened, is that actually the way that happened, and that happened both in SSRIs, and it happened in this category of emeloid plaque and Alzheimer's. And there's not always the incentives to go back and look at it. It's hard to make a name for yourself. It's hard to get the funding. It's hard to do other stuff. So this is all part of the process of science growing up. As much as we think we're so far ahead, there's many science, just like

politics, just like a lot of other things, can be influenced. And that influence can create group think. And that group think creates a place in a method where if you're asking questions outside of that, you're considered, you know, a pariah. And it takes, it takes courage to step outside of that. And I'm definitely not anybody that's involved with it besides getting a chance to interview people like yourself and your father, who's been a huge part of this process. Yeah. So I just wanted to, I just wanted to mention that and connect the dot. because it's like when people, it's important to understand how can science feel like it was so sure about one thing and then all of a sudden upend that. And that's actually part of the scientific method.

But the scientific method can get interrupted because of group consensus and group think and people not wanting to explore things. I just like to say I appreciate your humility in this, but I think you are part of this discussion. If you think about how many people have listened to this podcast, have learned from you over the years, I think you are a major part of this conversation about how do we reframe what it means to be healthy, how do we look at additional variables that we should be taking into account in a given day that can empower us to be healthy. I totally agree also with the inertia piece of things. There is a very strong desire to preserve our default consensus reality.

And that is a version in which a doctor like myself knows certain things speaks about things in a certain way and doesn't do other things. So we talked before about the fact that I've used psychedelics. That is a big deal because we're so closed off to the idea that doctors can be human, that I could have mental health issues that would benefit from, you know, learning about new modalities. I'm always of the mind that if a person is really significantly struggling, that kind of conventional medical care is still, the standard that I would recommend. However, if you consider that the majority of people right now in the United States are suffering from at least one chronic disease, and they will suffer from those for decades. And as I mentioned, that hundreds of millions of people around the world are suffering for mental health issues, and you appreciate that the default way of, or the

expectation for what is going to look like for a person to go through their life in the modern day is in many ways kind of miserable, meaning that a lot of things that happen are unnecessary. Then I think you have to be willing to challenge it if you want to have a chance at something else. And this is kind of the crux or the cornerstone of why I care about this at all. Why would I be motivated enough to talk about things that in some circles would have me branded as being a bad doctor or putting out information that isn't 100% science-based? And the reason for that is because I believe that we're not doing a good enough job, that health care can't be the sole arbiters of wellness.

It doesn't make sense. This health care system is based on, as we said before, when a person has a problem, putting them into an algorithm that is based on risk mitigation as far as the negative outcomes from that outcome. I was talking to our friend Jeff Bland last night at dinner, and we were talking about what does a society look like that is focused on wellness rather than disease. It's very different from what we see right now. We operate in a way that people will focus on the immediate gratification.

Don't worry about their health until something goes wrong. At which point, they have several options. They can choose an alternative, integrative functional practitioner, go to a conventional medical doctor, get a prescription, have a procedure. But that can't be where our conversation about health starts. Because if it is, we can't expect any outcome different than what we're seeing now. People suffering from these preventable diseases around the world, that are, again, the biggest issues as far as health and disability that exist.

So if we're willing to say this isn't good enough, and we're willing to say that we know enough to at least have a conversation about alternatives, I think it is kind of our responsibility. And I include you in this to have that conversation in a way that people can interact with the information. Because in the absence of that, we have to continue to expect disaster. So I think the curiosity is key. It's asking, well, what might I be missing here? I don't think it necessarily means trying everything under the sun and expecting that all of us are doctors just because we watched a YouTube video. But it does open the door to questioning what is best for us. And I guess the last thing I'll say on this is an individual isn't an algorithm,

right? And so as many data points as you might put into that algorithm, risk stratification, for a person, they're always going to have different data points that are going to work best for them. And in an ideal world, if you're listening to this, if you're watching this, you're thinking about what can I do to improve my health? What can I do to improve my brain health? And I want to make it very clear, there is a lot that can be done. And it doesn't have to be some sort of revolutionary new transition towards a 60-day detox. And you're going to do this incredibly exclusive diet. And you're going to go to Tulum for a month and you're going to regenerate yourself. That's great. But it's the simple things that matter. It's getting good sleep. It's exercise. It's making these

dietary changes. It's modifying the stressful inputs that go into your brain that over the lifespan, I believe will have the highest chances of achieving what I think is a successful life. It's maximizing that area under the curve. It's having those experiences that are meaningful. And it's not letting yourself be sucked into these negative cycles that perpetuate poor health that most of us at this point, our victim too. Well said. And you hinted at it previously and you were talking about looking at the inputs that we bring in. Media is obviously a big part of that. We chatted about that a lot last time. And also, I know you share this viewpoint, but right before I got here to this podcast that we're doing right now, I had my Thursday men's group. And it's a group of guys that

have known for the last seven, eight years. And all we do is we get together. We go, Usually we pick a hike in LA. We're very lucky here. You have all different types of hikes and can walk along the beach and whatever. We start at 7.30. We end right on time at 8.30 and we get there. And usually there's a question of the day or something that people want to talk about. If we haven't seen each other in a while, we don't get together every single week.

But, you know, often like 20 to 30 weeks out of the year, which is pretty a lot. We'll just talk about like, what are we celebrating and what are we navigating? And the subtext of a lot of our conversation is everybody's going through the human experience. Everybody's going through their own relative ups and downs in life. You're not alone. And we don't all need somebody to come in and tell us exactly what to do, but we do all need somebody to hear what we're going through. And upping the quality of friendships that you have in your life and surrounding yourself with better people who actually will listen to you, but also encourage you to take responsibility, personal responsibility

in your life. Because responsibility is such a powerful word. If you, I made this thing up. I literally just like made it up. I don't think I stole it because I Googled it and I don't see anything that existed about it. So I'm going to say that I made it up. But I called it the law of responsibility.

And I said, the law of responsibility says that if something is your fault, that's a good thing because that means that you can be part of the solution. If it's your fault, great. Now I played a hand in it. Doesn't mean that I caused it. Doesn't mean that I was the person that made it happen. Didn't mean that I caused myself to have depression. No, no, but I played a role in it.

Okay, great. Even if I didn't know how my actions, behaviors, whatever could have played a role in it. It's not about blame. It's about responsibility. That's a great thing because now I can take action. And a little bit of my beef with the sort of modern day, sort of politically correct conversations around mental health is it's primarily about let's talk about mental health. Great, beautiful.

Let's talk about how everybody struggles about mental health. Yes. Okay, great. What's the solution? Access. Access, access, access, access. Our system is literally imploding because there's not enough practitioners. the primary solution is still SSRIs.

There's a little bit of openness at more progressive places and doctors like yourself who are treating things differently. And so access is kind of this ubiquitous term that's thrown out as if access is the only solution that's out there. So everything in the mainstream mental health space is a little bit scared to lean into the personal responsibility side because they feel like it's getting too close to the. blame, which is completely different topic. And they're trying to just lead into, it's all about access. Just get people in the hands of a good practitioner. And that practitioner will solve their issues. And yeah, listen, I want people to have the best access they can have. I want people to have health care. I want all those things that are there. But we have to at some point in time, say that we look at all the stats. We look at this being the number one problem out there in the world

and increasingly growing from here. And it's like, we're not getting any closer to things working out. We need a fundamental different approach. So that's my soapbox moment. So let me build on this. Yes. You said two things that I think are very closely related. To start with, the assumption that medical care should begin in the clinician's office is

nonsense. It makes no sense. Why would we assume that if all we're doing is disease mitigation once a person gets to the office, that that's a strategy. All it does is wait till the moment things go wrong and then try to slow the rate of decline. It's very impractical. So for many conditions, including depression, that's the standard of care. It's you do whatever you want in the world. And then when things go wrong, let's make sure you have access to. When it's finally bad enough. Exactly. When your body's giving you the eviction notice, that's when you know. When on most days, it's really noticeable. I mean,

It's like a wound that gets infected. And at some point you say, you know what, this is really a problem. It's painful enough. I need to go get it looked at. That's kind of the way we've operated as it relates to when you should seek or even consider health care. But you talked about this connection that you have with your friends. And I do think one of the big insights I've gained from the last decade or so is having somebody who can hold space and listen is hugely important for mental health. It was actually done in a Mendelian randomization, which is a complicated way.

of doing research, they looked at what predicts people's risks for depression. And having people available to confide in, to listen to what was going on in our lives was one of the strongest predictors of lower rates for depression. And I think that's something that we're missing. We've gone to all these low-touch interactions. Somebody commented on my Instagram post or, you know, I bumped into somebody on the sidewalk. We said, hi, for a moment. That's very different from holding space for somebody, listening to what's going on in their

life without judgment. And I do think it is rare in circles of friends, especially in male circles of friends, to have the vulnerability to say, I'm going to tell you actually what's on my mind. I'm not going to sugarcoat it and being upset about my sports team's loss. I'm going to tell you about what's actually problematic for me. And the other person not trying to solve it. I think there is, you know, this may not be a piecey thing to say, but I think there is a male tendency to solve problems. I see this in myself. Somebody tells me about what's wrong in their life. I say, here are some things that I'm thinking about as far as solutions. And I have learned repeatedly, that's not what people are looking for. They just want somebody to be there, present for them,

to share in that experience with them. So to tie this back together with what we're saying about when health care begins, when mental health care begins, just like with diseases of metabolism, what we have to address is what's happening, not in the clinician's office, but what's happening in the outside world. If the outside world is toxic, we're never going to solve the problem by bringing people into a sterile environment and trying to pull out those toxins. We're not getting too many of the real issues. And so I do think that we all need to be empowered to make changes to promote our mental health and allowing your medical provider to be the only person responsible for you being healthy makes no sense. It's not something that is within their skill set.

It's not something that's even possible. So we talk about the drains on the health care system. I mean, prevention model is where we have to go. But again, for mental health, the idea of preventive care is almost not a conversation. We've started to talk about it with heart disease, right? People say, oh, eat a heart smart diet to prevent heart disease. People say take a daily aspirin to prevent heart disease, which, by the way, is basically an immunomodulating drug. Super interesting that about a fifth of American adults take an immunomodulator each day.

whether or not that makes sense for primary prevention for heart disease is another conversation. But the point being, prevention for mental health, I think, is first and foremost, as it relates to our health priorities for the planet. Overall, good brain health is the single biggest variable that will determine whether we as a species survive. So what are the actual existential threats? Take asteroids off the table for a moment. It's nuclear holocaust, right?

it is global warming. It's war. These are the things that are... Population decline. That's one that's getting more attention these days. Infertility might be an interesting one. But the point being, these are reflections of our brain state. And so if you're looking at how to maximize quality of life for the planet,

I think it's brain-focused interventions first. I think it's mental health focus interventions first. And that has to happen outside of the clinician's office, which has been historically not the place where we talk about those things because it's so sensitive and also it's something that, as you said, people don't want to take responsibility for their mental health issues. That is another conversation. I don't think blame is in any way a helpful conversation about what's going on with mental health, but biology is. If we introduce biology into that equation and say, it's your diet, it's neuroinflammation, it's your hormones, it's neuroplasticity, and to some extent it's neurotransmitters.

And those are things you can influence. You give people more opportunities, to positively impact their mental health without having to turf all of that to a practitioner that's just going to come in with a sledgehammer and say, look, it's this drug or psychotherapy, and that's what we've got. So it does diversify our shots on goal for an overall life of better mental health to offload some of that responsibility to the individual years before any sort of a diagnosis. But I think in addition to things that we can do during that actual diagnosis. working out dialing in diet. In fact, you probably put diet as number one because it's something that we interact

with on a daily basis. It's something that so quickly can easily throw our mental health off. And it can also start to take our mental health in the right direction from everything that we know about inflammation. Is that accurate? Would you add anything to that? I've said this before. I think the quickest way to improve your brain state is sleep.

However, taking that off the table for one second, I think that diet can be really challenging to dial in right. For many people, it's going to take a while. And I think as far as speed of action, the quickest thing a person could do to dial in their mental state is actually paying attention to their neurologic inputs as it relates to their sensory data, eyes and ears. What news are you watching? What are you paying attention to? Are you surrounded by negativity? That's it. We are on our screens about 12 hours a day. And how is all that stuff stressing you out? That's it. I mean, we can see in real time that if a person watches news, they become stressed. And what we don't see, but is really, I think, incredibly valuable to understand is what happens to your brain when you're stressed by the news lasts for a long time afterwards.

There's a kind of a well-documented effect of what stress does to the brain. It creates tunnel vision. It creates a singular portal where you're looking at only what's right in front of you at the exclusion of everything else. That's a very practical strategy if you have a danger in front of you. But if you're being constantly stressed, you're not able to engage with the rest of your environment. So now all of a sudden you're not able to think about what I should eat for my dinner tonight. You're just going to eat whatever's closest. Now all of a sudden, you're not thinking about I should call my mom because her birthday is coming up. You're only focused on what's right in front of you.

And that's usually the screen and whatever that screen is putting into your brain. So I think as you look at the most rapid ways to modify your brain state, it's paying attention to the inputs that come in through your eyes and through your ears and being conscious of the fact that for the most part, those are consciously defined or crafted by institutions, groups, whose goal is not your brain health, whose goal is basically keeping your eyes on the screen through sensationalism and fear and stress. And if you can shut that off, even for a little bit, that is a massive opportunity to reclaim some of that mental real estate. Amazing.

Right up there, I'll toss in one other one that's become a favorite of mine. And it's one of those that's often underrated. And I would say that's walking. You know, again, there's a whole list of in the toolboxes. I was just talking about one of my favorites. I would definitely put sleep just like you. Sleep is huge. So many people have terrible sleep.

Diet for sure. And I think especially for a lot of people who have a very sedentary lifestyle, just this general feeling of feeling stuck in their life, which that building up over years and years and years can be some of the root factors that ultimately can play a role in, you know, clinical depression and other things, you know, even if you're not clinically depressed. There's plenty of people that have not been diagnosed and just feel a general sense of called the blues or a deep sense of, you know, melancholy. And there's something about just getting up and going for a walk, especially if you can go with another human being that you love and appreciate and other stuff.

And if anybody's familiar with like the work of Francine Shapiro and EMDR and everything like that, the idea of like your eyes scanning the horizon and that letting your nervous system know that, look, no matter how bad today was, no matter what your boss said to you, no matter what fight you got into or whatever you're stressed out, you're letting your brain know by walking. And this is what she documented through her work. You're letting your brain know that you're making progress. Like you're making progress. And it's all okay. Like you're going to figure it out no matter how bad things are. And walking is one of those underrated things. You know, just going for a little bit of a walk in nature or a long walk in nature. It's just one of those things that immediately puts me in a good mood. Yeah, I think that's one of the biggest reasons why I'm an advocate of dog ownership. I mean, there's a lot.

I love my dog for so many reasons. But he will let you know. It's time to go out, not just so he can go to the bathroom, but to walk. it's time to move your body. And humans are so good at suppressing these natural urges that are essential for our well-being. He will tell you, he will come up to you and he will whine and say, it is the hour. He'll go over a stand by his leash. It is the hour.

And that's the type of stuff we just forget, right? There's these natural patterns, whether it's circadian rhythms, the sunlight that we get into our eyes. He goes first thing in the morning, he'll lay in the sun. He loves that. And there's so much to learn from that. The other kind of correlate to that is the nature. nature component. And so I know we've spoken about this a bit before, but I believe that our

kind of removal from or divorcing from nature is a fundamental aspect of what is driving poor mental health. If you look at what we've replaced our nature exposure with, it's scrolling on social media. It's watching stressful news. Like I said before, 12 hours of a day for American adults are now spent on screens. That's basically every waking hour interacting with one form of screen or another. So first of all, those screens are putting in a whole bunch of stressful and otherwise not super healthy data. And second of all, we've removed the healthy and kind of judgment-free zone, which is the natural world. And I think just, you know, the research has been stunning as far as nature helps lower stress, but also nature helps improve our decision-making. And it doesn't take a lot.

I'm always in favor of the zero-cost interventions. And this isn't a supplement. This isn't a pharmaceutical. This isn't a program. This is basically just getting outside as opposed to being inside. And so to your point about nature or about walking, I would say walking is amazing. Urban walking is awesome. But if you can move your body in a natural setting, you're getting the dual benefits of the exercise, the moving of the muscles, all the benefits that confers. But then also, there's something about nature exposure that helps calm the mind, something about the inputs coming through your senses, coming through your lungs. That has a very positive effect on our brain state and mental health. So I think that's just putting that in the

menu of things a person could do. Consider in a given day giving yourself a 15, 20 minute dose of vitamin N. And that is a positive, again, free intervention that has been clinically shown to have benefits for our brain health. Well, Austin, some of my favorite interviews are the ones where just like, you're reminded about the power. We all know the low-hanging fruit that's there. But it's like, you sometimes need to just hear a conversation where you get, it's like you're, hype person to reinvest in those basic things. I can imagine longtime listeners of this podcast. We're going to talk about a lot of the things that people knew. And there might have been something that they forgot about it. It's like, did we get you excited about it? Did we get you excited again to take

a walk or to text your friend that you haven't seen in a little while and catch up with them and really hear them or have them hear you about some of the tough things that they're working through? Anything else that you want to mention to our audience before we go into just highlighting some of the projects that you're involved with right now. I always like to give love to the things that are guests are up to. Yeah, I think, so this maybe jumps ahead to those questions, but for whatever it's worth, I started off in internal medicine, so managing chronic diseases, and then I've done a lot of things since then. But as far as a central and fundamental finding to all the, I don't know how many papers I've read at this point and all the things I've written, is just that empowering yourself

to put your brain health first is essential. It is the thing that we need to do. And in the modern day, unless you do that, your brain, your brain's function, your brain structure, will be written by the prevailing winds, the foods, the influences, and that's not a good thing. So just coming back to kind of tie this together as it relates to what we've talked about with serotonin, with diet, with inflammation, with gut health,

these are all variables that we can take upon ourselves to optimize. But I would say more important than trying to dial in everything and becoming the quintessential biohacker is just having the understanding that you can be in control of your health destiny, your brain destiny, with simple steps, but it necessitates becoming a little bit of a rebel as it relates to the default way of operating. And that's really key. If you're doing things that are going to be the most healthy for you, you will be judged as weird.

You will be seen as somehow deviating from the norm and unsafe. And that should be your expectation. If you're eating foods that are good for you, people will say, what's wrong with you? If you were prioritizing sleep rather than going out with friends to drink, people will say you're antisocial. And I would just say, having gone through that myself, I don't know if you can relate to any of this, that should be the expectation that this isn't necessarily going to be. a walk in the park, even though a walk in the park should be part of your plan. Because we are a sick, you're an unhealthy population. So doing what is necessary to preserve your own health, to preserve your own brain health is going to feel at least initially awkward. It's going to feel at least

initially like something that is weird. And that's the way it's supposed to feel. It's a great reminder. And it's a reminder for those people who feel like they don't yet have that friend group or family group that is supportive of them. And I think that that adversity also is good in a way because it pushes you to be serious. Now, I don't want somebody to experience it forever, but it kind of forces you to be strong in why you want to do these things. And what is your why? What is your purpose? What is your reasoning? Which is going to differ for every person. Let's go back to projects. Tell us about some of the things that you're involved in. Anything that you want to give a shout out to? For sure. So I'm lucky to be involved in several projects

right now. One of the ones I'm most excited about, which I alluded to earlier, is we're doing a clinical study where we're looking at how polyphenols influence epigenetic expression related to immune cells. That is a mouthful and a half. And we don't have to go into all the details of what this means. But listeners may know through some of your other people you've had on the show and through some of your conversations that one of the biggest areas of interest in medicine right now is the appreciation that our genes are not our destiny because the writing on top of those genes, which determines how they're used, which is a science of epigenetics, may be a principal determinant of our health. So this is, there used to be a way of looking at it either nature

or nurture and talking about our genes were kind of what we were given from our parents and then you might have some life experiences, but those are the two big variables. And what we now know is that our life experiences are influencing our gene expression. So really, really interesting. This may actually be a central pathway by which lifestyle interventions can reprogram our health. As it relates to what changes gene expression, we're understanding that there are specific molecules in our food, one of those groups being polyphenols, which are these plant-based anti-stress molecules, that may program our epigenome, or epigenetics for a more healthy state. And here's the extra wrinkle on top through the immune system. The very fascinating correlate here is that

as we age, our immune systems age too. They become more inflamed. They become more called senescent. So they become more dysfunctional. This is zombie cells. And we may be able to reprogram our immune health through the science of epigenetics. So this is a complicated study, but what we're looking at here is whether an intervention of polyphenols, these plant nutrients like rootin, quercetin, luteolin, can help to modify a person's epigenome, can help to modify their biological age, can help to modify their immune cells and signals. So we're finishing up the study right now, but I'm super excited to see how this works because it's one of the first studies that's ever asked this question about how do plant nutrients actually influence health beyond

sure, they're antioxidants and, you know, sure they might lower inflammation, but do they influence our gene expression? So that's, that's one project. And how is that measured? How are you measuring that aspect? Is it some of the, like, DNA methylation test? That's exactly what it is. So when you look at how you measure epigenetics, usually what you're looking at are methyl groups, which are short carbon groups that are attached to our DNA, basically. And so depending on whether those carbons are present or not present, it changes the way that that DNA is used. And the analysis we're looking at is going to look at more or less about 1.6 million sites per person. So about $850,000 on the front end, $850,000 on the back end. We use sophisticated AI to kind of parse out

whether there has been a statistically significant change at the pre and post periods of this study. But the bigger question, which I think is the important piece, is to say, we know that people who eat certain types of diets, who eat certain types of plants tend to have better health outcomes, but we don't know exactly why that is. And we've kind of gone towards, oh, well, it's more vitamins and minerals, or it's more antioxidants. And that's, that's, nice, but what is more important, I think, for us to understand to move this field of nutritional biochemistry from something that is, at the end of the day, just recommending people eat healthy foods because they tend to do better, to something where we're talking about targeted,

personalized interventions for your health is to understand what molecules might be influencing which pathways in our bodies. And so this epigenetic expression is a great example of how we can make that link. Beautiful. I love it. And if people want to follow along when you guys ultimately publish and keep in touch with that. Yeah. And so this is work that's being done through a company, Big Bold Health, the director there of science, a clinical innovation. So I'm running this study and some other projects. If you check out Big Bold Health's website, you can learn all about kind of what we're up to on the whole. We'll definitely do the press release and everything else once we actually know what the study shows. And so I don't have a ton of resources just yet, but by the

time you're listening to this podcast, it may be available. But generally speaking, bigboldhealth.com where you're going to find updates on our science projects that we're doing. We're doing several other projects as well. So we're putting together a summit. We're putting together a bunch of educational content. And the take-home message with this, the projects I've been involved with Big World Health for the last few years, is that we're really getting immune health quite wrong. We've talked about this before.

We're all fixated on the idea of microbe defense. But immunity is a principal determinant of our brain state. we've talked about that today. Immunity is going to be a major determinant of how long we live and the quality of those years. So this is getting to inflamaging immunosiniscence, zombie cells. And maybe most importantly, that there are now pathways by which we can help reprogram our immune system towards a state of overall better health. So that's immunorejuvenation.

And that's really the science that we're playing with right now. I do think that we will have some pretty interesting findings in the coming months. At the end of the day, the goal is really just to understand how are there more strategies that we can use to rejuvenate a person's health? And it seems like the immune system is a big pathway within that. So we're just trying to figure out which nutritional and lifestyle interventions are most potent for that and put that together in a programmatic way so that people can go, here's what's wrong with my state of immune balance.

And here's what I can do through these targeted interventions to bring myself back to a state of closer to equilibrium. And one of the ingredients you mentioned earlier in the podcast, you're talking about Hemley and Tartary Buckwheat. I just want to give a little shout out. You guys brought me. I don't know if it would be on camera. I guess I got this.

You guys brought flour. You guys are really trying to like introduce this, the company, big bold health. Obviously, you're involved in the clinical side and everything like that. And there's like the product team. There's an amazing pancake recipe that will link to. If you're look, if you're into pancakes and you're looking for. a healthier version of pancakes that you can make, check out this flower and check out the link in the episode.

I've made it a few times. My former assistant, she's been promoted, Yali on our team, she's made these incredible chai pancakes with Dr. Hyman. And our whole team is like absolutely obsessed with them. And this tardary buckwheat is what the base ingredient is. Yeah. I mean, I'll just, my slightly bias pitch, I actually love the pancakes too, Mark's pancake recipe specifically. That's the one we have on our website. I've made it a number of times and they are,

they're not like normal pancakes. They're spicy and also they're much more nutrient dense. So you don't need a huge stack of them, but they're fantastic. And to come back to this, so this is, again, it's not a grain. It's actually a fruit seed, which makes it, you know, gluten-free, grain-free, and also lower glycemic impact than what you would get if you were to eat a flour-based pancake, you know, conventional wheat flour. But this, we've had this plant kind of analyzed in a number of different ways for its phytonutrient content. It's also high in magnesium in zinc, but the phytonutrients for these polyphenols is actually what we're studying in this epigenetic study because what we've seen is that people who eat foods like this, as well as

who eat Himalayan tartary buckwheat tend to do better. So there's research talking about using this as opposed to other flowers for things like glycemic issues. There's research on inflammatory markers with the flour showing that people who ate it had lower inflammatory markers than people who ate conventional flour. But we're trying to figure out exactly what does this flower do as it relates to how it speaks to our genes. So the polyphenols that we're studying in this study are basically the polyphenols that are highest representation in this flower. And it's our goal to hopefully make this connection between what is this food, this kind of ancient food that people decided we'd rather have corn and wheat and rice and obviously much lower in nutrients

than this. But what's the connection between this ancient food and our health at the level of our genetic expression? So it's all just trying to say, how do we actually quantify and define how food is influencing our health at a much more nuanced level than just saying, eat more fiber and eat some more healthy fats instead saying, what does this specific flour do to our genetic expression as it relates to our immune system? But at a very basic level, yes, it's a delightful flower.

It's great in a whole bunch of recipes. You can find those on big boldhealth.com. We actually do phytonutrient analysis on every batch of this flour too, which I think is kind of unique. So we run it through some complex testing to make sure that we're meeting the polyphenol content per serving that we recommend on the back of the bag, which I find amazing. And also just at a very, very basic level, it's literally just an organic non-grained flour that is packed with nutrients. that are linked to better health. So it's kind of an overall win, but I'm really excited about the science behind it.

Yeah, fantastic. Your social handles for people to keep in touch? Dr. Austin Promoter on Instagram and on Facebook. And I think that's more than sufficient. I have a website. It's Austinpromoter.com. People can find me if they're looking for more there. Austin, a pleasure to have you back on.

Thanks for walking us through all aspects of depression, neuroinflammation, and a little bit about not just what's, wrong with the current system, but a path and a roadmap out that we can all participate in. Yeah, as always true, I appreciate the conversation. You're a deep thinker. You're doing amazing things to elevate our conversations around health. So it's great to be back. I'm sure we'll talk again soon.