192. Metabolic Psychiatry Toolkit: Measuring Ketones, Treating Insulin Resistance, and Using GLP-1s Strategically | Matt Bernstein, MD

Welcome to Medicine Redefined. I'm Dr. Altamasharaja and I'm Dr. Darsha. Let's put the hell back in the healthcare. Welcome back to part 2 with Dr. Matthew Bernstein. In part 1, we established the problem. Psychiatry is often treating a metabolic crisis in the brain as a simple chemical imbalance leading to poor outcomes. Today in part 2, Dr. Matt Bernstein returns to give us a solution. This episode is a masterclass on ketogenic diet as a medical intervention for serious mental illness. We move beyond weight loss and discuss how ketones serve as clean burning fuel that bypasses insulin resistance in the brain restoring energy to starving neurons. Dr. Bernstein breaks down the specific protocols used at his residential program accord, including that therapeutic zone, while aiming for ketone levels between 1.5 to 4 millimoles per liter is critical for psychiatric recovery and why 0.5 millimoles might be enough for anxiety or ADHD. We talk about the protein balance problem, how to eat enough protein to maintain muscle somewhere between 1.2 to 1.6 gram per kilogram without kicking yourself out of ketosis. And we talk about exercise as medicine, why resistance training outperforms aerobic exercise for depression and the power of high intensity interval training for metabolic health. Lastly, we also touch on the GLP-1 bridge and how some of these anti-obesity or anti-enerectics I should say are fascinating strategy where Dr. Bernstein uses these GLP-1 agonists like ozampic to temporarily help patients curb food noise and transition into a ketogenic diet. As a reminder, Dr. Matt Bernstein is a clinical psychiatrist and leading voice in metabolic psychiatry with 25 years of experience focused on full functional recovery. He graduated at Summa Cum Laude from Columbia University and earned his medical degree from the University of Pennsylvania. He trained to MGH and clean and help leadership roles in inpatient schizophrenia and bipolar care. He's now chief medical officer at Ellen Horne and created a cords comprehensive metabolic psychiatry program advancing the field through research, education, and national briefings. Whether you're a clinician looking for actionable screening tools or someone interested in cutting edge of nutritional psychiatry, this episode connects the dots between what we eat and how we think. All right, let's get into part two. Quick update before we dive in, I'm now seeing patients through my telemedicine practice refining health and performance. It's built around health span, longevity, and performance using the medicine 3.0 approach we talk about on this show. I'm opening a limited number of founding member spots. If you want to work together, go to refininghealthrx.com. All right, let's get into the episode. Matt, welcome back to this part two. A lot of exciting things that we talked about in the first part. And for those really just catching up, I'd advise you guys to go back and check out that first part of the discussion because I think it's important for us to get an understanding of why it is that we've been having this conversation. So that part of these clinical mental health issues and really just reframing how we approach this primarily symptom-based management strategy that we have. Actually, see where we can apply biology and make it more synonymous with our approach in a lot of the other fields in medicine. So I kind of want to pick it off right where we left off. We spend a lot of time talking about the role of insulin resistance and mental ill-hilt, I'll say. And you touched on something important. You touched on the ketogenic diet a couple of times and it's a powerful role. Now, the ketogenic diet is really interesting. Darshan, I've talked about this from a cognitive perspective and it's benefits in that my wife is a neurologist and so we understand the role and fact she's an epileptologist. So with its role in seizures and refractory seizure stuff, that's been mentioned for decades at this point. But the psychiatric component is something that I don't think is talked about as often. So what does it make sense for us to start? Does it even make sense to you know, I'd actually be interested to look at or understand your perspective on how you define ketosis, what that is. You did mention there's a certain marker that you trace. So what do you want to take it off? Sure. Yeah, let's talk about ketogenic diets because it's really exciting actually. It's like, you know, it's a diet. You know, people think, oh, how could food be that powerful to heal some really serious condition? But it turns out that it really is this very specific diet. So we got to get into the details a little bit. So ketogenic diet is eating most of your calories from fat, modern around a protein and very little of calories come from carbohydrates. So you know, that's really important. People think ketogenic diet and they think, oh, high protein diet, you're eating protein all day. That's actually not going to put you into ketosis. You actually have to eat most of the calories from fat. When they first invented this diet for kids with epilepsy, they were using a very high ratio of fat to protein and carbohydrate. It was a four to one ratio. So literally 90% of the calories were coming from fat. And we've learned over the years that that's not necessary. We don't need to have it be that extreme. So we can do more like a 1.5 to one ratio of grams of fat compared to grams of protein and carbohydrates. Maybe a two to one ratio for some people who are not reaching enough ketones with the 1.5 to one. But typically we start people at 1.5 to one and we can get a good enough level of ketones. And it's a biomarker that we could actually measure in mental health where we usually have prescribing medications and I have no biomarker to follow at all. I can't test the blood to find out if the medication's working. I can't check to see if there's enough blood levels of medication. Whereas this we can follow it really well and it really tracks very nicely with clinical response. And so it's an easy test. People can get one of these machines similar to looks like when someone's checking their blood sugar. They prick their finger and we put the little drop of blood on a little strip and we put it in the machine and we can get a level of beta hydroxybutyrate which is one of the most important ketones. And if we if our level is above 0.5 that's considered clinical ketosis. Usually for mental health we're targeting levels of above one or 1.5 and anywhere up to four or so. So we have a nice range there where we know there's a nice therapeutic effect and people do really well in that range. And so we really can see is the intervention we're trying to do creating the right biological response that should then correlate to a good clinical response which again like I was saying we just don't have that in the rest of mental health unfortunately. So the floor for you is one and is it this okay typically and I should mention too that the ketone levels do fluctuate throughout the day and they're usually lowest right in the morning as someone's waking up. They have that dawn effect with a lot of elevated cortisol that will suppress ketones right initially. And so if they're checking first thing in the morning we're not going to get levels of 1.5 or two most likely. Usually the levels are lower but when we when I say one or 1.5 we're usually checking late afternoon or early evening after dinner and usually that's when we get a nice level. The levels actually keep rising all through the night and they're actually at their maximum at about three or four in the morning before the cortisol spike that's coming for waking up. And so I've seen we actually have access sometimes to continuous ketone monitors and I've seen someone's traces which are really interesting because you can see them in the morning this person's were often around 0.3.4 in the middle of the night they were often up to four. And so if you check them around dinner time they were maybe 1.5 or two but you know and that was great. This person was having a wonderful clinical response to a serious mental illness but if you check them in the morning you would think oh he's not making many ketones but it turns out there's really quite a bit of variation throughout the 24-hour cycle. I was recently revisiting this topic as I mentioned and initially I thought that you have to be at one to be clinically in ketosis and then I came across some work of other people who said that technically actually even 0.5 and above technically push you down but what you're saying is this is more for the benefits exclusively from a psychological health perspective is that what you're saying? Yeah that's what I'm saying. Technically above 0.5 is considered clinical ketosis or medical ketosis but just in general from a for most people are coming at this to try to treat a more serious mental health condition we'd like to get it higher than that in the late afternoon or evening caveat being if you're checking in the morning you know 0.5 might be great that might be plenty and what would you turn it's really go higher if it's first thing in the morning. Is there a problem with being in 6 or 7 in that range? It's not dangerous unless someone is taking insulin or is a type 1 diabetic and then we'd be worried that they're moving into some kind of diabetic ketoacidosis but there's a lot of feedback mechanisms that will prevent someone who's not a type 1 diabetic from going into ketoacidosis and so usually they get up really high like that and there's these self limiting mechanisms that'll bring it back down. In fact if the ketones get high enough you actually make an insulin response if you're able to make insulin and that will naturally bring the ketones back down so there's sort of a feedback mechanism that protects you. So you know some people do get them up that high I've seen them up around in the 7 range. It's not dangerous but I think it's not ideal for functioning and feeling at one's best usually. Right more isn't necessarily better in this case. Yeah that's right. You had mentioned that the brain is roughly 2% of body weight. Consumers more than 20% of energy. That's right. It's a very energy hungry organ. Correct. And glucose is one of the main resources ketone of course being the other one. Can you speak a little bit about mechanistically why ketones are better fuel for the brain and with respect to these psychological diagnoses I know that we're kind of trying to buck them into bipolar and just for the purposes of studying this stuff. Which specific phenotypes seem to respond best to that intervention? Yeah two great questions. Let me take the first one first. So the fuel to these neurons and mostly we're talking about neurons here. These are the main cells in the brain that are communicating information. They're supported by all these other types of neurons as well. But let's think about neurons. They become insulin resistant. This is why we're so we care so much about insulin resistance. And we know that all mental health conditions, most neurological conditions have brain insulin resistance as one of the main features. So we know that exists. And what that means is that there can be glucose surrounding that neuron but the glucose can't get in to be used as fuel because it needs an insulin signal to get glucose into the cell. And we can't get that insulin signal if there's insulin resistance. ketones do not need an insulin signal to get into a neuron. They just float right in. And so that's the main benefit here is that we don't need we don't need an insulin signal. And so there's constantly, if you have ketones around, we never will have that neuron go into an energy deficit because of insulin resistance, which is happening. We think all the time in these mental health conditions. And so that's this idea that we now have this additional source of fuel. It doesn't require an insulin signal and it will always be able to make up for the deficit that might be there for that neuron if it was just relying on glucose. So that's really important. The other important part about this is that ketones are a cleaner burning fuel than glucose. And so we're going to create less oxidative stress and therefore less neuroinflammation. And so this is also very, very important in terms of as a fuel source, this is a as a preferable fuel source. Maybe let's stop there and see if there's any questions about that because that's there's a lot to that. I already just said. Yeah. Yeah. No, I have some follow-up questions regarding adherence. And I also wanted to talk about the protein aspect that you mentioned. But yeah, let me actually, let me just go ahead and do that now. Right. So one of the things is we recognize adherence is very difficult. So you said a lot of fat, very low to nearly no carbohydrate. And this is another interesting thing. I have conversations with patients with people and they'd say, oh, I'm on a no carbohydrate diet. And when you ask them really what they're eating, they're not counting the carbohydrates that's in fruit and vegetables. They're not counting carbohydrates. You have carbs and all these things. Right. And that's a very different than being on a ketogenic or true ketogenic diet. I think for the average person, probably you're going to need to be less than 50 grams of carbohydrates a day, which if you're eating a lot of veggies, you can get there pretty quickly. Yeah. So there will be some people who will talk about net carbohydrate. And I'm kind of curious where you stand there. You know, what might think with this has been, and like I said, this is something that I've really thought about getting into. And even exogenous ketones from a cognitive perspective from being sharper, especially like when we're doing this later in the day, when I don't want to use caffeine, the thing is the reducing protein intake. So Darshani, we're fastener, we're physiatrics, we're really recognize that age-related muscle loss is inevitable. And we want to hold on to that as much as possible. And for context for you, I'll tell you like I had a surgery nearly 19, 20 months ago. And after that and being immobilized for lower extremity for some time, I lost nearly 17, 18 pounds of lean body mass. And so we, when it comes to insulin sensitivity, when it comes to creating a metabolic sink in our body, muscle is the greatest tissue that we have. We know this, right. And so it's a bit of a catch 22 when you're not feeding that muscle, we're not laying down that protein to get those building box, especially if you're training and you need to be in an enabolic state, you need to be in a repair state. And then as we start getting enabolic resistance, how do you balance that? How do you think about that aspect of it with respect to like not getting somebody to gluconeogenesis? Yeah. Great question. And I agree 100% about the importance of skeletal muscle for longevity. It's so important actually for mental health as well. And so I'm constantly asking people to do resistance training. It's actually the form of exercise that's the most beneficial for depression is resistance training far outperforms aerobic training. In fact, so big believer in building muscle as well. And what I'm talking about is not a low protein diet, just to be clear. I'm just saying we can't go crazy with protein. So the RDA says 0.8 grams per kilogram of protein per pound per day. And that's too low for almost everyone. And so some people who are really in the fitness world, people are trying to build tons of muscle will go way higher than that. They'll go up to two or even three grams per kilogram of body weight per day. And that would be too much to produce ketones. And so what I'm talking about is some moderate something in the middle here. And so from most people, that's like 1.2 to 1.6 grams per kilogram of body weight. And that's sufficient to build muscle for sure. It's not going to optimize muscle building. Like if someone's trying to become Mr. Olympia and bodybuild, they're going to say 1.6 is not enough for me. And I say that's fine. We just won't be able to produce ketones. We got to choose something things sometimes. But for most people who are just trying to be healthy as healthy as they can, live as long as they can. And they're really working. If they're in the gym working out, they're going to be able to make ketones at 1.6 grams per kilogram. No problem. And for the person who's not training that hard, 1.2 is probably adequate and they'll still be able to make ketones there. So that's kind of my range for producing enough to build muscle, but also enough to be in ketosis. So yeah, that's really important. I'm glad you brought that up. Matt, I keep coming back to this chicken or egg question, right? So I'm assuming we don't have the studies. I mean, so when we talk about ketogenic diets, we're talking about from a treatment point of view, right? Correct. Yeah. Do we have the research to talk about it maybe from a more prophylactic point of view? Because you know, a lot of these podcasts that listen to Tim Ferris, for example, he has a strong Alzheimer's predisposition from his family. So he talks about going keto. Now, do we know that you actually have to have, you know, metabolic dysfunction, insulin resistance, then use a ketogenic diet to kind of bypass that, to kind of, you know, give the brain a different type of fuel to work better. Or can we actually just start with the ketogenic diet outright and prevent these diseases from occurring? I think we're just not there in terms of proof for prevention at this point. However, I similarly believe that there should be a preventative effect, given what we know about these mechanisms. And if someone was at high risk, I would certainly advise them that this is potentially very helpful for them in terms of prevention. We see it in dementia, you know, in mild cognitive impairment, there's definitely the ability to reverse some mild cognitive impairment with a ketogenic diet. Once someone is already at the point of, you know, dementia diagnosis, it's probably too late at that point. If probably we've lost too many neurons at that point, you're not going to bring back neurons that you've already lost. And so that's one way to look at it. The other way to look at it is you think about the extrapolation from the epilepsy world. We're talking about young kids. And those kids haven't developed severe metabolic dysfunction yet. Yet their brain is, you know, having seizures, right? And we know the ketogenic diet can treat that. And so we don't have to think about this only in the context of severe metabolic dysfunction. We can think about it as this is simply a is with epilepsy. And now we're seeing it in people, you know, young people that I see in their 20s. Some of them, their blood work looks just fine from a metabolic point of view. Their home IR looks great. And they don't look like they have any insulin resistance on their blood work. And yet the ketogenic diet can completely change the course of their severe mental health condition. Things like, you know, bipolar diagnosis or schizoeffective disorder diagnosis, things that medications have a hard time treating. And these people have tried multiple medications not gotten benefit. And then they get benefit from a ketogenic diet. And so we don't have to think about it just in the context of severe metabolic dysfunction. This diet seems to really improve brain health. And that's where we have to think about another mechanism, which is that these ketones are a signaling and molecule to mitochondria. And so that's really exciting as well. So we have this, you know, additional source of fuel mechanisms, but we also have the mitochondrial mechanisms that really, you know, could also be just as important. We don't really know yet. The science is not out on which one's more important than probably both important. But we don't have to just think about this for severe metabolic dysfunction. So coming back to the phenocyte that respond best from a treatment perspective, depression, anxiety, bipolar, what are we thinking? So I've seen the most dramatic results in more serious mental illnesses. And these are people who are the most motivated in some ways because they've already been through multiple hospitalizations, multiple medications. And the medications they're now being prescribed are usually a cocktail of three to six medications that are causing them pretty severe side effects. They don't like the way they feel on these medications. When they've tried to come off of them, they've often ended up back in hospitals or with more severe symptoms. These people are very motivated. And I've seen the diet be extremely helpful in those folks. And we now have a number of pilot trials and case series of people with serious mental illnesses. Probably the one that's been studied the most is bipolar disorder. And that to some extent makes some sense that if it's really good for epilepsy, there's a lot of overlap between epilepsy and bipolar disorder in terms of the phenomenology, the mechanisms, but also the types of medications that are used. Most of the medications we use in bipolar disorder are anti-apleptic drugs. We've seen that over the years. And so there's a lot of reason to think that this would be a condition where it would be very helpful. And it turns out that it's the one that investigators have chosen to study the most. And so we have a lot of good data in bipolar disorder. But we're seeing data. And like I said, psychotic disorder is like schizophrenia and so effective disorder, severe treatment, resistant depression. We're seeing data in severe OCD. And people ask me, oh, well, would it work for my ADHD or anxiety disorder? Yes. In fact, you know, it's you may not even need to get as high a level of ketones for it to work for that. You know, we could shoot for even a lower level of ketosis and something like ADHD or milder modern anxiety, milder modern depression would be fairly easy to treat with even a lower level of ketones. I think the other thing that I've come to learn is all right, it's not either utilizing glucose all the time or ketone all the time. Metabolic flexibility is a phrase that seems to be very important when you're just talking about health in general. And so the glucose ketone index is also something is my understanding, is that something that you pay attention to or if so, like how do you use that in your practice? Yeah. So the glucose ketone index is an interesting thing because essentially it is looking at how much of the fuel is coming from glucose versus how much is coming from ketones. And so the lower the index, the lower that ratio, the better. This has mostly been used in investigators who are studying ketogenic diets for cancer, actually, where it's also been studied quite a bit. And there does seem to be a really important use for it there because in cancer, we're trying to not only provide ketones, but we're really trying to starve these cancer cells of glucose. And so the lower the glucose, the higher the ketones, the better this intervention is going to work in cancer. We don't have that same level of data in brain health at this point. And so we're not typically using GKI, although it may turn out that it is something that we should be paying attention to. But so far, at least we're looking at trying to just get those ketone levels up higher. And typically when you're doing that, the glucose levels are also getting much lower. And like I said, for some people, we're starting out that they're not metabolically unhealthy anyway. So I typically put continuous glucose monitors on all the people who come into my program. And it's very common that the glucose will just be flat. And we just see them, you know, between about 70 and 85 and they don't go anywhere, you know, eating a ketogenic diet. They don't go higher. Occasionally, they'll go a little bit lower when people are first transitioning in. But once people are adapted to it, they just, it's almost like a flat line, the glucose curves. And so it's really more, we're just thinking about how high we're getting the ketones at that point, you know, the glucose isn't going up or down very much. Yeah. Have you ever personally experimented with the ketogenic diet? Oh, yeah. In fact, before I prescribed it for anyone, I put myself on a ketogenic diet. And that was about five years ago. And I've been in a low level of ketosis ever since then. I pretty much do it continuously. I'm not shooting for high levels of ketones. I should have shoot for about between 0.5 and 0.8 or so. That's where I typically am based on how I eat. And I love it. I sometimes say I feel 20 years younger than I did five years ago before I started this. Yeah. Really keeps you feeling young and energetic. I can do way more in the gym. I can do way more work throughout the day without it feeling challenging. I don't have to worry about, you know, eating. If I don't have something I want to eat or if I'm in traveling and there's nothing good to eat, I have that metabolic flexibility. I can just skip a meal. Before I did this, I was definitely insulin resistant. I could never skip a meal. In fact, I used to eat snacks in between my meals, so I could keep my glucose up. And it's really been liberating from that point of view as well. What about the use of exogenous ketones? Yeah. It's a great question. And there's a lot of interest in developing exogenous ketones. And it makes sense to me in some ways, because it's very hard to get people to do this diet, and especially people with dementia or more severe mental health disorders. This might be very challenging to organize. You know, there's may not be a setting where it can be done or there may not be good enough executive functioning. And my sense is that we can get some benefits from exogenous ketones, but not nearly all the benefits that we're getting from a ketogenic diet. I don't think we'll ever be able to truly reproduce all of these benefits with exogenous ketones. And there's two reasons for that. One is that we can't keep the ketone levels up all day long, all throughout the 24-hour cycle, using exogenous ketones. The longest that some of these products may last is about four hours or so. And so you have to dose some probably three times a day, at least to keep the ketones up during the daytime, and then overnight they're going to go back down again. So we will get some of the benefits of the signal that ketones give to the mitochondria. We'll get that benefit. We'll get that some benefits in terms of this additional source of fuel at times during the day. But what we're not going to get, and this is sort of the second reason, is that we're not going to get that reversal of insulin resistance. We're not going to get that reduction of insulin and all those other fundamental metabolic changes that you're getting by removing carbohydrates from the diet. And I shouldn't say remove. I knew you were asking some questions before about what people can eat. We should get into that a little bit because it's not as strict as in a 1.5 to 1 ratio. People definitely can eat a lot of non-starchy vegetables, and they even can have some berries, some fruit, and still keep themselves in a state of ketosis. Yeah, this is getting me thinking, I need to start fasting. Get back to my 24 to 36-hour monk fast once a week. I did enjoy those. But would you say prescribing the ketogenic diet, how do you actually apply that to your patients? Now, I'm assuming it's patient-specific, but is there something that you usually tell them to quick start whether it's a fast or certain foods? How do you get your patients to implement this diet? So yeah, it really depends on the setting and the person. So if it's just an outpatient setting, and I'm not working with a dietitian, it's just me and that person, and I'm counseling them, I often will start them off just by, let's just start with a whole foods diet. Can you do that? Let's just remove as much ultra-process food and severely processed food as we can. Then we'll say, let's cut out other sources of sugar, if we can, at that point. Once we get to there, let's cut out some starchy vegetables, let's cut out bread, let's cut out rice, and then we're pretty much there. Then we have to add in fat, we have to just remove people's fear of fat at that point. We've all been taught that fat is dangerous, fat's going to give us heart disease, we have to reduce it, we have to remove it, or fat is going to make us fat. All these things are not true, but everyone is walking around with all of those ideas in their mind, and so we have to relearn what fat does and how it works and not to fear it. And then, so once we're there, then we can start thinking about macronutrients. So we want to get their carbohydrates down to about 30 grams of carbohydrates per day or less for most people, and we want to figure out how much protein that person needs, in that 1.2 gram per kilogram or 1.6 gram per kilogram range, get a sense of that. And then, essentially, if the person is fairly healthy and active, we can just say, eat fat to satiety, basically. So if you're still hungry, eat more fat at that point, if you're not hungry, but you don't have to keep eating fat. And if someone's carrying around some extra body weight, especially some fat, they can make ketones out of their own fat. And so if they're eating a little bit less and they're in ketosis, they don't that hungry, I don't force them to keep eating more fat, they can make ketones out of their own fat. Once someone gets down to a normal weight and they have a low amount of body fat, they're going to need to add back in eating some fat at that point. And then, usually, we're kind of good from there. But the way I just described it, that's someone who's got good executive functioning is observant, can make changes in their life. And so different settings may require a lot more support than that, depending on the person. I love this. I mentioned to Dars just because I do love, I find myself to somebody who does well on somewhere between 150 to 200 grams of carbs a day. But there are times in life where you just something keep coming up over and over and over again in different context. So I just think this is all the sign pointing that I do have to try. I'm actually looking at the keto moja right now at the very least, maybe I'll start with the good one, keep it indexed to see where I'm at. And how much I need to do to get that that 1.15 kind of where you are. I love how we're walking down the lifestyle medicine pathway. I think it's necessary. It should be the foundation as opposed to putting it toward the barrier. And so let's keep walking down this pathway. Unless, do you think there's anything else within the nutritional realm that we need to explore with respect to this or do we cover most of it? I think we covered most of it. I just want to point out what just the one quick question you had about net carbs. Oh, yeah. So this is really important because net carbs is calculated by taking the carbohydrates and kind of subtracting fiber from that and calling it net carbs. And people can definitely get into trouble in terms of, you know, being able to achieve ketosis if they're just focused on net carbs, especially if they're eating packaged foods that have they say low net carbs, then you look at it and you see, well, there's actually quite a lot of carbohydrate in there because some of those net carbs or some of those carbs that, you know, are actually digestible and not all fibers the same. There's many different types of fiber. And so we're fine subtracting the carbohydrates in vegetables because vegetable, the carbohydrate there is really not digestible at all. And so that's fine. But there are these other fibers that they put in these packaged foods. And so you have to be careful because a lot of those actually are digestible fibers. And so there's a whole industry now of keto food you can buy at the store, keto cereal, keto granola. You just have to be a bit careful about just focusing on just the net carbs and things like that. Yeah, that's a good point. Thank you. So after a nutrition, we talked a little bit about the role of resisted training exercise, other pillars that when I look at that, of course, sleep. We've talked about the importance of that. And if I'm just going down the lifestyle medicine thing, I'll just use the American cause of lifestyle medicine. They talk about refraining from exogenous substances. I want you to stress because that's kind of the main lens that we're looking at it within the psychiatric illnesses, I suppose. Where does the literature point to with the best evidence for these mental health conditions that we've been talking about? I'm sorry. Can you repeat that the best evidence for what exactly? Well, I'm assuming like we've talked about nutrition afterwards. Yeah. Is it exercise or are we talking about, you know, where would you go next with a person when if you're prioritizing by the state of the evidence after nutrition? Yeah, great question. So absolutely exercise there is absolutely an enormous literature on exercise and mental health. It's incontrovertible that exercise is very effective for things like depression, anxiety, ADHD. So many of the psychiatric disorders respond beautifully well to exercise. And we have meta-analyses that have more than 1,000 research articles in the meta-analysis. We're not talking about just a little bit of evidence here. We're talking about huge amounts of good quality evidence. The problem with just saying to people, you've got depression go exercise is that they really have a hard time doing it once they're depressed, right? And their diet's going to be working against them. And it's a really powerful tool and it's really synergistic with the ketogenic diet or a low carbohydrate diet in terms of improving brain health and mental health. Because many of the same mechanisms by which exercise improves mental health are the same ones in which we were describing ketogenic diets. Reversing insulin resistance, increasing BDNF, lowering inflammation and improving mitochondrial health, all of that is achieved through exercise and ketogenic diets. So there's tons of overlap and synergy there. And so that's definitely where I would go next. And combination of different types of exercise, aerobic and resistance training, throw in some sort of mind-body kind of exercise like yoga or Tai Chi in there if they're able to do all of those things have their own unique benefits for brain health and mental health. What's the program look like at Accord when they're coming before like four weeks at a time that intensive? What's the exercise prescription look like there? So we have a personal trainer that we work with who we send people to twice a week. And he's often getting people restarted or started for the first time on an exercise program that hopefully they're learning about how to do this and how to continue it when they leave. That's the idea. And it can be different for different people. I mean sometimes he's starting really basic and you know but some people have an exercise history and he can go a little more advanced. We're also getting people walking a few times a day every day at the program for multiple reasons. One is that you know we're talking about glucose disposal before. When you use muscles after a meal with it you know no matter how many carbohydrates you had whether a small amount or a large amount that glucose is going to get disposed of mostly in the muscle. And if you're moving those muscles there's this glute four transporter that comes to the surface that will bring glucose into the muscle without needing insulin. So we get glucose disposal without insulin if you walk after a meal. So that's a really important thing for people to start practicing and once they're doing it and getting in habit of it hopefully they continue that throughout their lifetime because that has tremendous long-term benefits. And so you know it's usually the combination of the walking and you know a couple times a week with the trainer and then if we get people really interested we're trying to get them to go to the gym at other times during the week as well and we've had a number of people who have started to do that and the more someone exercises the more benefits we see typically within the program. I love it. Yeah especially the piece about resistance training being given more important right I think that there's a lot of attention appropriately paid to the value of steady state low intensity exercise some people call it zone two whatever zone you want to call it. However when we just look at the literature it actually turns out their resistance training is probably more beneficial not from a mental health perspective alone but also it just helped the aging and downstream you know muscle loss things that we talked about and just longevity in general so when you think about health span I think that's probably more important it's all important. We're not seeing one as necessarily more important actually I guess we are saying that or at least I am. Can I ask you go for a quick real quick Matt would we look at exercise what are the endpoints that we're looking at like are these self-reported symptoms that we find that are improving or is there a specific I mean obviously the metabolic markers I'm sure are but what else are you really looking at typically in these research studies that I was referencing they're looking at mental health rating scales so they're looking at like reduction of depression on a HamD or a Madras or a PSQ 9 or something like that. We're talking about symptom rating scales typically that they're using as endpoints there's probably better measures in that but that's typically what they use. Yeah in those studies. Yeah got it. Yeah I'm curious is just like I mean when I go work out or you know somebody gets more aesthetically in shape you might see more opportunity or see themselves fit in the world better and have more agency to kind of do things that they want to do so curious to kind of see is it a direct correlation or is it more kind of just you know we start to exercise when you start to get maybe that self-confidence you start to kind of see the world differently so to speak. Absolutely I think that effect is real but I don't think that that's usually what they're measuring in these studies which are a little more short term so we get the direct effect and then we get all these other ancillary effects as well I think we get it all when we exercise. There was one thing that we get people to do for their health period it would be exercise for sure and then I think we shouldn't also leave out high intensity training too which has its own unique set of benefits and especially for people who are busy if you can get people to do some high intensity training huge benefits in a short amount of time usually we can't start people there because we don't want to injure people if they're really just starting their fitness journey we can't get them to do a really serious high intensity interval training workout but the evidence for that is tremendous and I think there was a paper that just came out that showed that typically people think of high intensity as sort of twice as effective as moderate intensity but now it's like seen to be like ten times more effective than moderate intensity which is really music to my ears because I'm really I like to be efficient at the gym and I like to just really go hard for a shorter amount of time and there's really now evidence showing that this is there's real science behind more benefits in a shorter amount of time yeah I wonder first thinking about the same one I think on a Patrick recently had a journal club episode on this it might have been a paper in nature if that's the one you're thinking about yeah so we'll find that and we'll link it yeah it was really mind-blowing talking about how maybe one minute of high intensity interval training was equivalent to like over a hundred and fifty minutes of walking or something like that with respect to specific metabolic ill-health dysfunction type things right so metabolic versus stuff so that was really fascinating I want to switch to drugs now let's talk about some pharmacology again you know in research uh or while preparing for this like you know I came to realize that or at least came across some evidence that actually looking at some of these uh diabetes drugs as mode tools right um and essentially talking about how insulin sensitizing and ingredient-based therapies can improve mood in some patients and you know it was interesting they're some of the mechanisms up looking at inflammation energy-sucking and pathway things that we've talked about in the first half of this discussion not just glucose lowering systemically so um I want to kind of get your understanding and how you prescribe them if ever do you ever use these I guess off label for you know like a mental health condition so I have prescribed them some and you know I think there's a couple of contexts where it makes sense one is in someone with a serious mental illness who has been on psychiatric medication and gained you know a tremendous amount of weight caused you know lots of metabolic dysfunction in them you know we often see people gain sometimes unfortunately 60 80 pounds from some of these at typical anesthetics and mood stabilizers that people get put on and um so I think in that context you know we're really talking about you know improving someone's health span and lifespan tremendously if we can put them on one of those medications and have them lose that weight and you know generally a lot of benefits there um the other context I've used it in is people who are trying to do a ketogenic diet for their mental health condition but they're just having trouble with intense food cravings they're having trouble actually being able to do the diet and so in that context the idea would be to use a lotus of one of these GLP1 medications for a temporary period of time as a bridge transition into getting on a ketogenic diet and then the idea would then be withdrawing the GLP1 medication and so I've seen that work really well in some people too people just couldn't follow the diet but then they get on the medication they follow the diet we can withdraw the medication in three to six months after being on the diet and um and at that point they're they're they're bodies adapted to being ketosis their lifestyles adapted to eating those foods and we do really well at that point yeah I love that yeah just I guess I took this for granted but for the listener specific drugs that I was thinking about as a metformin right that's been mentioned time and time again improves insulin sensitivity a lot of people look at it as a longevity agent quote-unquote and Puebloodisone is the other one I got the mechanism of action for that one specifically but increases insulin sensitivity again those have been directly been studied for some of these mental health conditions yes I get a reasonable amount of evidence suggesting that's improvement of symptoms and some of those symptomatic things that that you're talking about dorsh the GLP1 thing is really interesting a lot of people will use the term neuro inflammation right I don't really know what that means do you yeah it's just inflammation in the brain essentially right there are markers of inflammation in the brain and we know that actually a lot of these mental health conditions include a neuroinflammatory component in fact there's some studies on depression if someone had they they've done studies a population of people with major depressive disorder and elevated CRP or highly sensitive C reactive protein and they've given those people anti-inflammatories I think they've they use celacoxid in those studies and they've actually reduced depression just with celacoxid in those people in that population so I mean that really shows that there there is an inflammatory component I think there's actually multiple studies where they've done that how long do you know if the top area how long was that I don't remember the time frame yeah I'm sorry to say I do want to go back to metformin though you know I've prescribed a lot of metformin over the years because that was the drug that we would typically use for people with weight gain and metabolic dysfunction from using a typical anti-psychotics so I've prescribed tons of metformin over the years and I would say that it's weak in that context in terms of a metabolic improving agent even at the highest doses of metformin we typically don't see a lot of improvement in metabolic markers and weight in that specific population and I've seen no improvement in mental health from metformin in that population and so at this point if someone's gained all that weight and has metabolic dysfunction I would move more likely towards a GLP1 medication than that for that context and I should also say there's some evidence even though a metformin has been studied for longevity the jury's still out there on longevity I think and there are studies there show that metformin has some negative effects on mitochondrial health and so they take people and put them through an exercise program with metformin and without metformin and the people with metformin had did not get the same metmitocondrial improvements as the people without metformin and so that concerns me and so if someone is trying to use metformin as a longevity drug I always cite that study because I think it's enough at least for me to say look the jury's out on longevity but we know it's going to have negative effects on your mitochondria and if you're exercising and trying to do everything you can for your mitochondria you're actually working against yourself by being on metformin for that reason the one case so coming back to what if somebody's on a ketogenic diet and is that a time when you would avoid a GLP1 because that could get really tricky right well no that's what I was saying to people who are trying to do a ketogenic diet but failing because they're having such cravings that's when I would use a GLP1 drug to help them transition onto the ketogenic diet with on a low dose of a GLP1 with the express purpose of just transitioning onto the diet and then withdrawing the GLP1 after three to six months of someone being on the diet and succeed succeeding on the diet so I think that's a really important use of GLP1 for my specific population people who want to do a ketogenic type or just to have too much food noise they're on a medication a psychiatric medications that's causing them to have more food noise they've got relationship to food and sugar that's been going on for many decades that they're having trouble breaking and so for those folks sometimes the GLP1 can help them they're already motivated to do a ketogenic diet it'll help them get there and then we can withdraw the GLP1. Love it. Do there's anything else on here before research? No I think I'm good here yeah I'm going to set it for the next step. Yeah so as I mentioned like we were talking about offline right so a lot of what we've been talking about is biology based management right that's kind of the first part of the discussion was and I had mentioned to you that I Dr. Daniel Aiman I've heard him at least on two podcasts and one recently on the checkup Dr. Mike was an interesting conversation will link that he's been an advocate for the past 30 some long years talking about the importance of brain health in fact he wants to get rid of the term mental health he thinks is stigmatizing and maybe that's the case I suppose I nobody wants to be called mental and the interesting about him is that he's scanned the brains of hundreds of thousands of people and in some sense he advocates for the importance of getting a spect scan those who don't know that's a low dose CT basically brain CT that's looking at blood flow and which parts of the brain are lighting up which are not lighting up but the implications of that I'm not really sure he'll explain that a little bit more he's written a couple books about it and so that makes a question you know got me thinking a lot about most of the things with respect to musculoskeletal health with really a lot of other specialties we do rely on imaging a lot because we're looking at the anatomy we're looking at like the physiology with that regard and it comes to mental health we haven't really done that and we've been making this case for biomarkers for a lot of things that are going to help us improve upon our decision making process and I'd love to get your thoughts on that philosophy is that something that you use do you see there is a role for it now maybe in the future where do you stand on that yeah it's a great question you know what I would start with that is that a spec scan as you said is looking at blood flow and what is blood flow a marker of but metabolic health actually how much blood is going to an area is how metabolically active that area is and so if we see an area that's either too hot it's getting too much blood flow or too cold it's getting too little blood flow that's really correlates with hot and cold amounts of metabolic processes right I think the the utility of spec scans for us now I think is just not quite there we just don't have enough data and I know he's done thousands and thousands and he thinks that he can help guide treatment but my sense in really observing the treatment protocols coming out of his clinic is that the spec scan doesn't actually guide specific treatments yet we're just not quite there yet I wish we could be at a point right now where we could say a specific brain area requires a specific treatment but the reality is that it's metabolic dysfunction when you see an ugly looking spec scan of the brain and that we need treatments that improve metabolic health which is the basic things that I'm describing here and we don't have specific metabolic treatments that target one area of the brain versus a different area of the brain at this point and so I just don't see the utility of a many thousand dollar scan that we can't get insurance to pay for at this point I hope that at some point we will be at that level of specificity of different brain areas but I just don't think we're the area yeah I think if anyone chooses to let us into that doctor Mike episode with the data layman that was exactly the pushback that he was giving him was that not enough data there's no randomized controls trials to figure out what is the threshold for treatment how do you know how quote unquote sleepy a part of a brain might be and then I think the protocol that data even uses too I don't it sounded like it wasn't it was kind of a hey here's a bunch of different options pick what you kind of want to do we have TMS we have exercise we have some medications we have supplements as well and here are the rescue benefits of all them now let you at the patient kind of decide what you want to do so I'm guessing we don't have like a surge of protocol per se when it comes to understanding you know what part of the brain might be when what sleepy or overactive and how to treat that it's such a what you're saying as well that's essentially what I'm saying yeah and I think if we had and that's from seeing a number of the reports that have come out of the clinic and no matter what areas the brain are lighting up you almost get a very similar protocol coming out of it and I also have a pretty similar protocol for almost anyone who comes to me but I think my protocol gets at a root cause you know it's a hard protocol to do I'm not I wouldn't mince words that I'm not asking people do some I'm asking people to do something that's challenging but I also am asking people do something that I know is going to improve the metabolic health in their brain and therefore improve these symptoms that they're suffering from so and regarding you know think about these as brain health disorders rather mental disorders I'm all for that but I think I don't want to totally define for people how they want to see their own issue some people come in and you know they feel like it's their issue is in something that happened in their childhood and I don't want to take that away from someone but what I will say is that probably did have is having effects on your brain that include metabolic effects on your brain we know that adverse childhood events are highly correlated to later on mental health disorders but also are related with metabolic health disorders so we know just how important the metabolic piece is but I also think that people really want to and I think they deserve the right to define their own suffering in the way that helps them you know and is less stigmatizing to them so for some people calling it a brain health disorder is less stigmatizing for other people that's more stigmatizing so I think we just have to be careful with our language depending on who we're talking to how how expensive is the spec I don't know for sure but I think it's quite pricey a brain spec yeah because I kind of I guess I related to like the full body MRIs that people can now choose to get do you yeah are you opposed to people going out let's say they have the money they want to get a scan of their brain or scan their body are you opposed to that type of imaging or do you just let people kind of choose to guide their own I don't have you I don't I don't meet people who are going out and getting a bunch of spec scans very often I think Dr. Amin's clinics are one of the few that are really trying to promote spec scans of the brain as a as a tool for helping people with these types of conditions or symptoms I don't see it as something that people are otherwise promoting that much I think there's a lot of companies that might promote like full body MRIs for example but I don't think there are that many that are promoting spec scans and I don't know of any psychiatric providers who are ordering spec scans routinely on people unless they have a spec scan as part of their protocol and part of their clinic yeah what about functional MRI same thing same thing yeah functional MRI is a research tool at this point we're not using functional MRI in in diagnosis or clinically at all at this point awesome so let's see if we can kind of put this all together right for somebody who might let me just reverse what I just said a little bit in that there is one protocol that uses functional MRI which is there's a TMS protocol that was developed at Stanford called the Saint Protocol and in that protocol they do use functional MRI to try to figure out which areas of the brain to target with the TMS and then so in that protocol and that protocol has been shown to be very effective in treatment resistant depression however there are other protocols that also do an accelerated version of TMS like that Saint Protocol does which is really like you know it's about 12 weeks of TMS in a week so you're really doing TMS all day long for five days and there's other protocols that don't use a functional MRI that also get really good results in treatment resistant depression and so it's a little unclear to me how important the functional MRI is those other protocols my understanding is they're using the TMS machine to map the brain a little bit and just to find out where the magnets should be placed and my understanding is that those are also quite effective in treatment resistant depression and I've seen them be quite effective without using the functional MRI so it's part of that Saint Protocol but that's kind of the one place where it's used clinically that I know of at this point. I love it so I'm hoping that some general practitioners primary care physicians are going to be listening to this maybe even some psychiatrists and they're hearing this they're thinking cool but I don't run a metabolic clinic right dimension I don't have time to sit here have deep deep discussions about understanding people's lifestyle and what type of nutrition they're on and maybe there's a strong knowledge gap and we've talked about this time again this is not something we spend time in medical school learning right hopefully if they're listening to this podcast we we're filling that knowledge gap for them but for that person who's listening what are something that you could say next week what are three things that they can start on what are some baseline labs that should be non-negotiable before or during psych meds what are some key questions that they should be asking to distill down the understanding of what this person's metabolic health might be what are some actionable things you could say for them yeah so I think you're right that this is not necessarily an easy thing to replicate in a primary care visit that's five or 10 minutes or even in a psychiatric visit that might be 15 minutes or even 25 minutes but there are some things that people can do so I think before starting these psychiatric meds that have metabolic consequences we want to get a baseline level of someone's metabolic health we want to get a lipid panel we want to get an HBA1C we want to get a home IR home IR's I think I maybe said this before but should be part of an annual physical for every single person which it's actually boggles my mind that we don't have that as part of an annual physical we're just waiting for the HBA1C to go up that doesn't make a lot of sense from a preventative point of view because we can see alterations in the home IR 10 to 15 years before the HBA1C moves so we really would want to see that I think getting full thyroid panel can be really helpful I always get a vitamin D level these are all things that are just B12 level these are just some basic things that a psychiatrist would want to know to really rule out if there's some kind of underlying metabolic or medical condition before starting a psychiatric medication and then getting a sense of just does the person exercise if not can you get them to exercise some of these problems as we said can really be amenable to exercise and it's not just as little as you know please just go exercise like we really have to use our skills especially psychiatrists we've been trained to work on motivation and underlying resistances we should be using those skills for getting people to do things that are good for their mental and physical health so I would say that's one that I strongly believe in and sometimes even before I started talking about ketogenic diets I felt like for years I was spending half my day talking to people about exercise for their mental health and there's just incredible benefits for that what about in the inpatient setting are there any tips and tricks like that you could provide me as an inpatient rehab doc to try and get my patients that up in a way that when they get home they can at least take that lifestyle because again I'll fly we talked about how I had a patient with functional neurological disorder otherwise known as conversion disorder in the past and you know as you said they don't really see psychiatrists but we're at least sending him to a neuropsychologist yeah to get in-depth testing but I did have an insulin resistance that I level that I could check I do try very very hard with all my patients try and simulate a lifestyle medicine take an environment for them already doing the PTOT doing the exercise is sleep I try not to disturb them I told it to be a low stimulation environment diet yeah no I could pull so much there but you least you can educate any other tips or tricks from your end though how do I get somebody maybe set up with a metabolic psychiatrist after well there aren't that many metabolic psychiatrists unfortunately yeah hopefully we'll be changing that but there are some online programs that are focusing on metabolic and mental health now that people can start accessing and we can I could get you some of those links if you want to put them in the show notes on those programs and I think just really emphasizing like you know how important this is like you know you're having these issues with your mental health this is not something that you only want to focus on a medication for it maybe a medication could be part of it maybe psychotherapy could be part of it but really making that connection for people between their physical health their body and their brain you know this is where all this is coming from it's not just above the neck which is unfortunately where we've thought about all these things originating for so many years now that's kind of how all everyone thinks about them and so I think we have to as the physician in the room you got to change people's thinking that this is not just about what's going on in your brain and in your mind this is connected to what's going on in your body which is connected to your movement to your food to your sleep to your light you know all of that's important yeah absolutely well Matt we just want to say thanks so much for being gracious with your time I mean this is why we love doing this podcast everything we talked about was so actionable I think the audience is just going to take away a lot of nuance away from it too and kind of take some application and adjust their lifestyles you know I'm going to definitely get back to the fasting so I definitely appreciate your time before we let you go tell us where our audience can find you where they connect with you and maybe what's next for you sure so you know people can find the program I was talking about a cord at www.accordmh.com Accordmh.com ACC or DMH and then people can find me on LinkedIn I don't do a lot of social media but I do have a LinkedIn profile so if anyone wanted to connect with me individually and just had a question or they wanted to just connect they can find me on LinkedIn and I I like to respond to people have got any kind of specific question about any of these topics so those are some places to find me in terms of what's next I'm hoping to expand metabolic psychiatry offerings for people and just really try to create more options for people to access this incredibly effective treatment to get the support they need to be able to do that awesome love it last question we have for you Matt how do we put the health back and help care wow yeah and four years another hour but yeah I mean you know it's it's a great question because it gets at this problem we have which is that we are doing sick care in modern medicine now not health care and so it's really talking about the things we've been talking about today it's talking about diet and exercise and light and sleep because that's how health is created and in fact even that's how mental health problems can be reversed so not only creation of health but reversal of problems all comes from that so I think that's where we want to be thinking we want to be thinking about things that you know well what were ancestors doing not and I don't mean like a hundred years ago I'm talking about like you know 10,000 years ago before agriculture how were they living and how did they create health we know that they were pretty robust back then and they actually had bigger brains than we do now actually and you know one of the ways they did that is they were moving all the time to find their food they were fasting all the time because they couldn't find food and they weren't eating a whole bunch of processed food at all they weren't eating sugar very often and they were certainly not eating carbohydrates so if we kind of mimic that and they were outside a lot they were getting light all the time so if we mimic a little bit of that much of that as we can mimic in our modern lifestyle the better off we're going to be awesome appreciate about thank you yeah thanks Matt my pleasure thank you thanks for listening to the other episode of medicine redefine if you enjoyed this episode please be sure to check out some of the additional resources in the show please also check out our social media platforms where you can find more content like this you can follow us on instagram twitter and tiktok at med redefined we also want to thank our team for the production of this podcast specifically Ethan Jewel in video Harita Yeporian social media Zanablugmani our research and Sarah Hahn for newsletter oh and if you want to get similar bite-sized information delivered to your inbox every Sunday please be sure to sign up for our newsletter also if you enjoyed the show please be sure to subscribe review and share with anyone who you think will gain value from this as well now time for the ever so important 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