How Exercise Can Transform Mental Health and Depression with Dr. Nicholas Fabiano

With depression itself, we actually don't even know the mechanisms of what's causing depression. Low serotonin equals depression, and that's why we treat with these antidepressants that restore serotonin levels. But we know it's a lot more complicated than that.

Dr. Nicholas Fabiano is a third-year resident in psychiatry and is like totally making waves in terms of using exercise therapeutically to treat depression. He is a psychiatry resident and researcher at the University of Ottawa. He has been doing a lot of research on the intersection between mental health and physical health, especially in terms of psychiatry, and he's got a beautiful way that he talks about how to dose all of this.

Just challenging yourself. So whether it's exercise, whether it's signing up for a course that you think you can't do, even though during these times it's very difficult to get through, and even more so when you're in a depressed state, the fact that you're able to accomplish that and get through it no matter how hard it is, it gives you this what we call locus of control.

Dr. Nicholas Fabiano, what a great name. Welcome to the show.

Thank you for having me.

I'm so happy you're here. I stalked you a bit. So as I was telling offline, I have a talk that is unusual for me because I'm talking about the mental health benefits of exercise. And as I was digging into all the research about it, and I love the fact that I'm now going to medical conferences talking about exercise. First of all, it makes my heart sing. But I was like, you kept showing up and then I found you on a podcast. Now all of a sudden you're on every podcast.

Yeah, I've been busy lately.

It's fantastic. Exercise is finally having its day out there. It makes me so excited. Let's go back to how you, studying psychiatry, ended up with looking at exercise as a treatment modality.

Yeah, so it's a great question because it's kind of— in psychiatry, you don't always see those two going hand in hand. But my story—

you never see them going—

you never do. And I think we're seeing a tide shift now, but you don't traditionally, as you mentioned, see them go hand in hand. So a little bit of my own background I've always been into sports and different things like that. Like I played soccer throughout my life and in medical school tried to stay active and different things like that. And at first I was actually interested in going into more of a sports medicine sort of career, but I found when I was doing some of the electives in sports medicine and working with some of the varsity players, a lot of the concerns were more so surrounding mental health. So that was something that piqued my interest. And then, um, during medical school, unfortunately I had my own little bit of an accident as well too, where I was getting into the gym a little bit more. I started arm wrestling, not professionally or anything like that. And I ended up actually breaking my arm, uh, in arm wrestling. So I have a big scar right here, a nice surgical scar. Oh man. Yeah.

So those of you can't see it, he's like, his whole forearm is like a scar.

When I broke my arm, at first I didn't think it was a huge thing, but I noticed the impact it had on my mental health where I went from being able to do all these fun things, work out, and, and how important that was for my own mental clarity to now breaking my dominant arm, not being able to do a lot of the fitness stuff. I can't even write my exams and stuff because that's my hand. And to top it off, after I had surgery on it, I ended up getting nerve damage too. So my radial nerve was unfortunately damaged a little bit, so I couldn't move my wrist properly either. So all these things came down and I realized how important exercise and how intertwined mental health and physical health were for my own experience on top of this. Mm-hmm. And how important it was for my own recovery. From my prior experiences, from my silly arm break, Uh, it really led me to have a passion for exercise and for exercise specifically in mental health. And the most applicable one when I started looking into it was more so through the lens of depression. So that's kind of where some of my interests peaked first. But, you know, since then it's expanded beyond that, even beyond exercise, and it's more so applying but emphasizing these lifestyle parameters to mental health. So at the forefront with psychiatrists, not just at a, you know, population level from a prevention standpoint, but also from a treatment standpoint. So I had my interest, I broke my arm, and, and here I am now.

Yeah. Well, I love that you were out there talking about this. It is such an incredible thing that you can use in depression, in like— I have a son with a traumatic brain injury. We did a lot of exercise therapy to bring him back. Like, there's so many different places. I'd love to start really high level of just what some of the mental benefits of exercise are before we get into kind of more treatments and the different types and all of that?

Yeah, so in a general sense, there's a lot of different benefits for exercise. So even if we're not looking at it necessarily from a mental health perspective, we know that there are associations with a variety of different types of exercise and cognitive benefits. So whether you have depression, whether you don't, whether you're deemed to be a quote-unquote healthy individual, exercising regularly will lead to improvements in your cognition. So that means your ability to think through stuff, your memory, and all these different factors which are so important. The other obvious thing that we don't often think of in the realm of brain health is just your overall body health and how that goes hand in hand with your mental health and with your brain health. So moving regularly is so important for the health of your body. It also helps regulate things like your sleep. Staying active and, and being active throughout the day and in a regular interval is so important to regulate your sleep. Which, you know, moving forward also improves your mood and cognition and all these different things. And we know with exercise as well, there are different structural changes to your brain. So with exercise, an area of your brain called the hippocampus, which is very important for memory, has actually shown increases in size. And this is particularly relevant as we're getting older because we know some of these brain regions will actually shrink. So exercise can have a protective effect against some of this. And, you know, the topic of this podcast is, is mental health benefits. So diving into that with exercise, we see most of the literature is behind depression. So some of these antidepressant effects, but there's also benefits for anxiety. There's even benefits for more of the severe mental illness like schizophrenia from a symptom perspective or even cognition perspective. So, you know, we could probably go all day speaking about all the different mental benefits of exercise, but just to show that it's very important in, in a quote unquote healthy population, but there's also so many applications. In the field of psychiatry?

So I think back 30, 40 years ago, I'm totally dating myself, but back then we all thought the mental benefits of exercise were endorphins. Mm-hmm. And everything was about cardio back then. So it was always all about running to get endorphins. But I think the key point here is it goes way past that and through a variety of different types of mechanisms, right?

I think there's a large focus on the biological basis of exercise and the antidepressant effects. One of the things that I like to bring up is With depression itself, we actually don't even know the mechanisms of what's causing depression. It's previously been this theory or the serotonin theory where low serotonin equals depression. And that's why we treat with these antidepressants that, you know, restore serotonin levels. But we know it's a lot more complicated than that. I like to break it down into what's called like a biopsychosocial model. So we can speak about the biological things that exercise does from an antidepressant perspective. So we know that exercise increases some of those myokines. So how your muscles essentially communicate with your brain. And one of the important ones is brain-derived neurotrophic factor, or BDNF, which is otherwise termed as Miracle-Gro for the brain. So that's a very important one that, that we think is implicated in depression, and that's what leads to some of those brain changes that we've seen. We know that exercise also can reduce inflammations, whether that's peripherally or that that's centrally in, in the brain, which again is important because there are a lot of different inflammatory hypotheses for depression. So we think that maybe another mechanism exercise can lead to some of these brain changes where we see increases in the hippocampus, which in depression, sometimes we actually see shrinking, shrinkage of these brain areas. So those are some of the biological realms of what exercise is doing. But oftentimes we stop there. We stop at biological and say, okay, that's what exercise is doing. But I like to open it up a little bit further than that. One thing is the, the social aspect that I mentioned, and it's particularly important for people that are maybe rather isolated. Exercise may be an activity or the only thing that they're doing during the week where they're doing it with someone else. So whether it's a fitness class, whether it is being on a team sport, whether it's even just going to the gym and speaking to other people that are there, it's such an important part of exercise that often goes underrecognized, but it, it's hard to really separate the two unless you're doing an exercise that's completely in isolation. There's probably an element of, of being social that's contributing to the antidepressant effects because we know how toxic loneliness can be to your body, not even just mental health, but also the physical perspective. And then the other thing that I like to bring up too is through the psychological lens, we know that immediately after exercise, you have that almost boost in mood, and that can give you that motivational push to start doing other different things and, and to tackle your next goal. Those are some of the antidepressant mechanisms beyond just the biological basis. But I think they're so important to be aware of because we get so stuck in the biological sense, cuz it's the fancy one. It's, it's. Very interesting to talk about, but there's also the other realms that are so important too.

You know, I heard you talking about social on a podcast and I thought that actually may be the most important one.

Mm-hmm.

When you really look at this, I, it was kind of a running joke back when I was a personal trainer paying my way through grad school was I'd take clients and start working out with them and they would literally vomit up their whole life stories. Like all the stuff, like I knew everything going on more way. I was like, don't need to know all this. Like everyone's relationship problems, money, like all of it. And then I kept thinking, gosh, should I just go become a therapist? Should I become like the, you know, exercise therapist? Because it's— it does— there's something about movement that just gets people to start letting things go. Think about how effective that could be. Maybe that's a new form of specialty therapy. The challenge, though, that I see is, you know, and I think back, so I, as I told you, I had a son who had a traumatic brain injury. One of the first things I started getting him to do was to move. Like, and just kind of reconnect things. But some of the times now, as we've been working through it, is getting him to do it when he's not motivated, you know? And I have a friend right now who's in the big lower part of a bipolar stage. And I was like, could we just get out and walk up the stairs? Like, you know, it's so— someone who is listening to this who's like, yeah, but I don't wanna get off the couch. I mean, how would we move them from being completely sedentary to starting to do some of these things that are going to help?

That's a great question. I think there's not a clear consensus in research of what is the smallest amount of exercise to have an antidepressant benefit, but there is literature. And when you look at meta-analyses, which is when you bring the studies together, to suggest that going from sedentary to even moving just a little bit— so like you mentioned, whether that's just going for a walk, whether that's while you're at work, instead of taking the elevator, going up the stairs, and hopefully it's not too high up, but But just these little steps are so important because I think sometimes we get lost in what is optimal for exercise. Like what is the optimal intensity? What is the optimal amount? What is the optimal timing? Now that can become very overwhelming for, as you mentioned, like your friend that's at a lower point right now, that can seem overwhelming to the point where you're like, I'm, I'm not even gonna try this. So I think the emphasis needs to be placed on just doing any little amounts of exercise and using that as motivation to build. To the next stage and really shaping in a way that is, is something that you like to do. Because similar to diets, you can have a perfect diet that, you know, calorically, macro and micronutrients, everything's perfect. But if you don't like it and it's not sustainable to make, it's very expensive, you're not gonna do it. And the same principles apply for exercise and even more so when you're in a state where you're feeling more down or depressed. Any amount of exercise is better than none. And, and starting low and going slow will always be the best approach with something that you like. And it all counts is the good news.

Mm-hmm. Now, even though it does all count, and I've, I've looked at some of this literature and it seems to be skewing more on the cardio side, I think it's important to look at it because exercise is as broad a category as nutrition, where we have got vegan and paleo and carnivore, you know, and then you look at exercise and you've got everything from walking to sprinting to powerlifting and everything in between. So you have all these different modes. Are there different things that are really stand out in the field of mental health?

Most of the literature is based on aerobic exercise, so things like walking, running. I think that's the case because it's easier to conduct studies and safer oftentimes to conduct studies versus putting someone in a weight training class or something where there is, you know, maybe a higher likelihood of injury. And, and it does happen with running, weightlifting sort of thing. But when you look at, again, the meta-analyses which put all these studies together, there's not necessarily a, a clear winner in terms of Aerobic or mind-body. And let me, I guess I should describe the different classes and research base first before I kind of go into that. We alluded to one already. There is aerobic. So that's things like running. Then we have resistance, which are things like weight training. Then we also have mind-body, which are things like yoga. And to circle back to what I was saying is there's not a clear winner amongst those. The most important thing is adherence. So in the literature, it's dominated more by these aerobic studies, but it doesn't necessarily mean that they're better. When we're starting to put these studies together. So with a patient in front of you, or if you're just even listening and wanting to get into something, think about what you want to do and what would be interesting and whether that's something you've done in the past and, and you would want to pick it back up or whether it's something you've just seen online and you're like, hey, that would be cool to try. I would say go for it because ultimately you want to have that curiosity and passion to learn more about it and get into it. And that's what will build as you start to learn more. Rather than saying, you know, going to your doctor and saying you have to run this many miles at this pace, maybe won't yield as many results.

I will tell you, when I was in grad school, all of the research was done on cardio. Like, I actually went and did strength research and I was— it was hard to even find an advisor. Everything was based on cardio and it is a lot easier. You have class Monday, Wednesday, Friday, do 3 30-minute training sessions and cardio is so easy to control. You know, you do, you do wonder because I think Andrew Huberman was talking about this on his podcast. Cast of one of the things that happens with exercise, and you could do this with cardio, but it wouldn't be so much steady state. It's more like the HIIT or the resistance training of what happens to your brain when you do these hard things.

Mm-hmm.

Can you talk about that?

Yeah. So I think even though it's outta the realm of mental health, just challenging yourself. So whether it's exercise, whether it's signing up for a course that you think you can't do, even though during these times it's very difficult to get through, and even more so when you're in a depressed state. The fact that you're able to accomplish that and get through it, no matter how hard it is, it gives you this, what we call locus of control. Oftentimes with medications, you are prescribed a medication and there is a role for medications in depression and, and a variety of other mental disorders. But I've had a lot of patients say to me that, you know, I feel that this is almost external to me and I'm reliant on this thing that I don't control. Whereas when you're getting into something difficult, like whether it's exercise, you're, you're training for just running a short distance or a marathon, or whether you're weight training and you're setting a goal there, even if it it takes a long time to get there, the fact that you can look from where you started and look back and say, wow, like I really did that, that gives you that sense of control. And sometimes you won't even notice the mood benefits that happened along that journey. Again, that goes to say, you know, you were able to accomplish whatever your objective is, but also almost get yourself out of that depression. And I'm always careful when I discuss this point too, because it's not to say that people's depression are caused by lack thereof. Of exercise. Depression is a disease like any other disease. It can, it can happen like diabetes. There's risk factors for family history. Sometimes it just happens out of the blue. So I think it's very important as a physician when discussing with your patient not to have the tone that you currently are depressed due to lack of exercise, but more so, hey, this is a treatment option and maybe let's talk about it. But doing these hard tasks are so important because it gives you that sense of control. And for the future, then you know that you're able to do something again that maybe even is even more difficult.

Just between the social side of it and that feeling of accomplishment, knowing you can do hard things, those two things alone, if there weren't the actual biological things going on, those alone are huge. So are you actually in the place where you're diagnosing and prescribing at this point?

Yeah, so right now I'm in my third year of residency, so I've been doing clinical rotations since mid-medical school. So 2 years of medical school, then 3 years of residency, and I'm switching to my 4th year in, in just 1 month actually. So I've been doing it for, for a fair bit, not as much as obviously staff and stuff that have been doing it for a long time. But I think in this time, and even as my experience as a medical student, I've, I've been able to see how important this is for a lot of patients and also how it's not for everyone. I think that's where there's a soft spot sometimes where you try to promote exercise for absolutely everyone. And that's okay if it's not something you, you, you don't want to do, then there's a lot of other options. But I think my own clinical experience has been a lot of people value it and, and rank it as one of their most important features of their lifestyle.

So you've been, cuz you're kind of a, like you're sort of a renegade here doing this, right? I mean, you know, so you're now seeing patients and offering this as a treatment modality. What are you like, how are you doing that? And what are some of the things you're seeing by using this?

Hmm. So my approach to that, and we actually wrote a paper about this, is to kind of prescribe exercise in a similar manner that you would a medication. So when you're going to your doctor and speaking about a medication, you would expect to know what the medication is, the frequency that you're taking it, the dose. You would expect to have follow-up to see how the antidepressant response is happening. And what I found was there was a disconnect with exercise where a lot of patients would say their doctor would say, you know, just go exercise or just go run. And that is obviously very condescending to a patient because they know that they don't need to hear it again from someone speaking that to them, right? What they want to know. Eat healthy and, and, and then that, that can make you like not want to go back to the doctor. So what I thought was it would be helpful to have a, a framework to prescribe exercise similar to medication, not to medicalize exercise, but to make it in a way that You could speak to your patients similar to medication. So the framework for that is called the FITT framework. It's called F-I-T-T. So that stands for frequency. So that's how often are you exercising per week? There's intensity. So that goes from low, moderate, or vigorous intensity. And a simple way to measure that is something called the talk test. If you're able to have a full conversation, sing and everything when you're exercising, that's probably near low intensity. If you're able to talk, but it's getting a little bit more difficult, you can't maybe sing, you don't have that lung capacity, It's probably getting more near to a moderate, but if you're not even able to speak to the person beside you, that's probably closer to a vigorous intensity. Then there's the timing of exercise. So how long are your sessions? Are they quick 10-minute sessions? Are they an hour long? Are they longer than that? And then the last T is the type of exercise, which we've spoken about, is whether it's aerobic, is it resistance, is it mind-body, or is it a mix of them? Because a lot of different exercise types kind of are jumbled up and there's not a clear fit for different ones. So Using the FIT framework, you can speak to your patients. You can essentially prescribe exercise in a similar manner that you would for medication. But what's important is you can also follow up. So you can chart this in your notes. You can see what the patient has agreed to, to exercise, see how that's working for them from both an antidepressant perspective, but also feasibility. Is 3 times per week too much? Is 1 times per week too little? And adjusting based on that. And that really allows you to have a conversation more than just exercise. And I found that to be very helpful in the clinical practice.

Don't you think that part of the issue— like, you know, we hear all the time, and so my background is nutrition and exercise, and, you know, you hear all the time, well, doctors get an hour of nutrition. I'm like, well, that's interesting, they get zero hours of exercise. And honestly, I mean, how much can you throw at one person to learn, right? I mean, you know, like, exercise physiology is a whole separate subject. So, I mean, don't you think part of this is that a doctor has had no no training in this now all of a sudden. And that might be part of why they're not using it as a modality in order to heal. What's interesting for me with my son was one of Dr. Daniel Amen's, one of his docs, and he was like, let's have him do ping pong because that's going to help connect the dots. It'll help his brain. And then we also did HIIT training and all sorts of other things because I was reading the research. I'm like, oh, this will make sense. But I think for so many people, they didn't have any background whatsoever. How would they be able to put it in as a treatment protocol?

Yeah, no, it's a great point you make because based on the literature, what we see is people or physicians that are active themselves are more likely to prescribe exercise. So that applies to primary care, but that also applies to psychiatry, which speaks exactly to the point that you were making where people that are not doing those behaviors themselves probably don't have the expertise nor feel comfortable speaking about that to a patient. I think there is an issue at the educational level because, you know, repeatedly throughout medical school residency, we're told how important exercise is for mental and physical health, but we're not told how to prescribe it. So I think there's a big gap there. And yes, I think there's, you know, a lot that we're learning in medical school and, and different things like that. But I do see how important it is to learn. And, and do I expect physicians to have the whole physiology of exercise down and all these different mechanisms? Maybe not, but I do think it's important at least to be able to speak to your patient about prescribing exercise. Because when we look at exercise as a treatment for depression, it has similar effects to medications or therapy. And it's actually first line in a lot of different guidelines. With that, I think it would be, you know, expected that a physician would be able to provide a first line treatment to their patient. And that's where we're doing a disservice in training for, for different physicians because there is this first line option. We have the evidence to back it, but we don't have the training to, to allow providers to speak to their patients about it. So I think the first step is education. I think the second step is, at least in Canada I can speak to, we don't have a lot of streamlined methods to refer to allied health. So whether that's physiotherapy, whether that is a personal trainer or something like that. We don't have a streamlined process to give someone a prescription to go to the gym as easy it is to enter it into our computer for medication. Another problem as well is, is the incentive structure too. A lot of times in primary care, people are strapped for time. They don't have a lot of time to be speaking to their patients about different things like this. And even in psychiatry, there's not incentive for the physician, which, you know, you hate to speak about it from that lens, but we know that financial incentive result in change. So I think at a policy level, it would be great to see changes where if you're having a discussion with a patient, that there are incentives to do so. So there are now incentives to learn this, there are incentives to implement this in your practice. Um, so I think these are just a few of the changes that need to happen to see a change. I think it will probably take a while. I think the evidence is starting to build to say how important exercise is from a mental health realm, and even Common sense, someone would say that too. But I think it's going to take some time and really we need an educational reform to really highlight the benefits but also implement it into practice.

Well, so what is some of the evidence you've kind of— I'd love you to go a little deep on a couple of the studies to show how important this is.

So what on a large scale, and this is not the exciting one because it's the meta-analysis data where we bring together a lot of the studies they brought together. I'm forgetting how many studies now. I want to say over 50 in a meta-analysis. And what they did was they compared exercise to medications and therapy. And they brought all of these studies together, saw what their effects were, and they found in mild to moderate depression, there's really no difference amongst the different treatments for exercise. One of the more interesting individual trials though is, um, there was a trial in the, uh, Journal of Affective Disorders, I believe in 2024, and I'm forgetting the first author now, but essentially what they did was they compared running therapy to antidepressants. So a head-to-head trial. And again, they found a very similar anti-anxiety response, um, for running therapy as compared to medications. But the other interesting finding in this trial is that there were so many physical health benefits that antidepressants sometimes do the opposite to. So in the running therapy groups, there was benefits to weight, there was benefits to blood pressure, there was benefits to waist circumference, there was benefits to your heart rate variability. These are things that we often overlook in psychiatry, at least in our traditional sense of training, we, we, we monitor for some of these things, but we're not proactive enough because we know that antidepressants, we know that antipsychotics, they contain these metabolic side effects. I think there is a responsibility to do something proactively to prevent these, but also if there's a treatment option like exercise that not only prevents them, but does the opposite of, of making some of these parameters better, I think it's so important. So in summary, we see very equivalent effects for mild to moderate depression, but we also see multi-system benefits. Of exercise that even go beyond what I mentioned in that one trial. But we see changes to insulin resistance, we see changes to, you know, all these different parameters that are so important for our health. So yeah, I think these are things that are often overlooked but are important to discuss.

And it is— I mean, when you think of something like an antipsychotic, which the side effect is going to be insulin resistance and all the blood sugar instability, which then can sometimes create more problems in terms of psychosis when you've got blood sugar, you know, it's Just seems like a natural to have at least have exercise on board alongside it, you know. And I know it must be hard, there's no way to do a blinded study with exercise and drugs to be able to, to look at both of them. Any other places that, that you've seen besides, um, using it in depression, like you talked about schizophrenia and anxiety, but what other studies have come up that really are mind-blowing?

One of the studies, or two, that we've conducted was looking at an important parameter, which is suicide. So we were looking at exercise and we brought together the studies looking at what effect does exercise have on suicide? Because we know within depression, but across all mental disorders, people have an elevated risk of, of suicide. So it's, it's very important to see kind of what's going on. And we did two different meta-analyses. So one looking at randomized controlled trial data, one looking at population-based data, and we found a very similar trend where exercise led to a reduction in suicide attempts, but there actually wasn't a, a noticeable change in suicide deaths. Or, uh, the thoughts of suicide, which is interesting. It doesn't really necessarily make sense on, on first view. And, and what we thought from that was, you know, maybe the numbers were luckily too low to detect a change in, in suicide deaths. However, the alternative interpretation is that exercise is known to reduce emotional impulsivity. Um, and we know that a lot of suicide attempts are not these necessarily well thought out or planned attempts, but they're more so these impulsive reactions to a stimuli or something very horrible that happened in your life. And The thought is that exercise may reduce this emotional impulsivity and thereby reduce the amount of suicide attempts that, that one would have. So I think it's an important lens, lens beyond depression because we see, again, such a high risk of suicide across different mental disorders that it's important that we proactively address this as well too.

So I've also heard you speaking on creatine, which I'm a huge fan of. Like when I look at especially How do you exercise for this per— I, I don't know if you've had to deal with the perimenopausal, menopausal woman with all the mood swings yet. Mm-hmm. You, have you had that pleasure?

Yeah, I've, I've had a few for sure.

Yeah. Yeah.

Yep.

You know, when you look at exercise is such a key thing there because you've got insulin resistance starting to happen, cortisol going up, you've got them starting to store more visceral fat. But the other thing I've been really gung-ho there on is creatine. And there was that study that came out, I think, with creatine and creatine with SSRIs, I think they were using versus just SSRIs alone for depression. Are you familiar with that study I'm talking about?

Yeah. The study you're referring to is probably, um, Liu et al. Um, it's in the American Journal of Psychiatry. It was back actually in 2011, but it's had a resurgence of interest. As you mentioned, creatine, it's, it's more traditionally viewed through this muscle lens of improved performance, whether it's weightlifting, whether it's running. But because we know creatine also has cognitive benefits, there's been a resurgence of interest from a mental health perspective. So with Liu et al., what they did was they, as you mentioned, paired creatine with an antidepressant and compared it to an antidepressant alone. And this trial was 8 weeks long. And what they found was that at the marker of 2 weeks, there was an improved antidepressant response, and that went onwards to 8 weeks where they continued to see antidepressant benefit. And in that point, they only used 5 grams of creatine, which is impressive because we're starting to see literature that we may actually need higher doses of creatine to have some of these brain benefits. And I'm actually writing a paper with Darren Kanda right now. I just was finished writing it yesterday about why we may need higher doses from a cognition but also mental health perspective. One other thing that's relevant in this area too is we spoke about creatine plus antidepressants, but there was also a recent trial in 2025 in the European Neuropsychopharmacology that compared creatine plus cognitive behavioral therapy, which is one of the first-line treatments for depression, versus just the therapy alone. And they found a very similar trend where adding creatine to the therapy resulted in improved antidepressant benefits at week 8, which both of those are very exciting for me because creatine has such a favorable risk-benefit ratio. It's very cheap, it's very accessible by a lot of people. So it's very promising to see these early signals. One thing that I will say, and, and I've written about this before in some papers, is the evidence is missing for creatine plus exercise. For depression, which makes the most sense because most people that take creatine are doing it for exercise. So, the question that I would like to see answered is what happens if you combine creatine plus exercise for depression? We've submitted some grants to do a trial adding creatine plus resistance training. So, hopefully, we'll be able to get that up and running soon. But that is just to say creatine is a very promising supplement from the mental health realm, and I'm excited to see more and more research come out even beyond depression.

I'd love to see resistance training versus cardio to see if there's any kind of difference there, or if it's just movement matters. I just wonder if the intensity matters, the duration matters, like what matters here. I understand from an exercise prescription standpoint, telling someone just to go walk is the easiest possible. They're not likely to get hurt. It's easy to do. Anyone can— almost anyone can do it. So that piece is exciting. But I do wonder if there's something about both the doing hard things and the intensity may have, you know, a bigger impact. And you wonder if like some of that as we age, losing fast-twitch muscle fibers might be contributing to some of the issues with cognition, you know. So there's that. Then on the creatine side, I use a different form of creatine, and I met the person who actually discovered it. And so I'm using much lower doses to have the same— to get the bioavailability. So I use HCL, which is really interesting, ends up being about the same price point, but because you can use a seventh of the dose. But I have a feeling— I was listening to what you were saying in terms of timing, I think, yeah, that would be about when it would take. Because preferentially, you would think if 95% of your creatine's in your muscle and 5% in your brain, that it would probably get into your muscles before your brain, you know, even though it seems like it should go to your brain first, it's more important. It probably goes to your muscles first. And then you think about, like, especially in the women their tissue stores likely were lower to begin with because they're not getting what they need from animal products as much. They're probably not eating a pound of raw beef. So, you know, you just wonder if some of that— like, I wish there was a way we could really measure creatine levels in the body. That would be amazing. But I don't, don't think we've figured out how to do it. All I can think of is somehow overloading and then seeing some creatinine spillover. But I don't know how you would be able to tell. It does make sense. Like, it'd be great to know, does intensity matter? Is there a certain point of duration to hit a certain thing? And do you need to have kind of supra physiologic doses, like to make sure you're getting more to the brain? Is it in time of depression or stress that your brain might need more? These are the questions I would love to have found out.

Yeah. And I can speak to, I can speak to a few of those actually. So. Let's talk about intensity first in terms of exercise. The general trend, and again referring to the meta-analytic data, which is bringing the studies together, says that higher intensity, so the closer you are to vigorous, has greater antidepressant benefits. The caveat to that though is as we get older, it's actually more near the mild or moderate because you can imagine if you're, if you're 80 or 90 years old and you're trying to do a vigorous intensity exercise, you're more susceptible to have injuries or to have more medical complications as a result of that. So we see that in general the trend is higher intensity greater antidepressant effect. But the caveat again is, is as we age, we start to go more near the mild or moderate range, which is important.

Is that just cuz we have to, or is it like when you say as we age we go towards that, is that just because we've lost those fast twitch muscle fibers and we've slowed down and we're trouble getting that intensity?

It's, it's hard to say because a lot of this data is based on randomized controlled trials, so they preset what people's intensity levels are working at. And of course, You can't force someone to go to an, an intensity level that they're not capable of. So I think there's a little bit of bias there. So I think it's probably both of what are we capable of doing as we age, but also I think it is a matter of if you're pushing your body too far, it, it, it goes back to the curve that I mentioned where that curve is not the same for everyone. That is a, a general curve, but that shifts based on your age, based on any medical conditions you may have. That's why I'm always very careful to say that vigorous intensity exercise is always better because that's the general trend, but there are lots of caveats to that. So I think whether it's, again, medical conditions, age, so many different things, and that's why it's so important to have an individual exercise prescription for someone and not just throwing the book at them and saying, this is what the literature says, this is what you have to do. The other thing is, is, is creatine. What dose do we need for depression? And as I mentioned before, most of the studies have just used 5 grams. The problem with that is that's the dose for muscles. We know that some people will have their loading phase of creatine where they'll take 20 grams for about a week or so, then they'll go down to 3 or 5. And this is referring to creatine monohydrate. But does that work for the brain? And, and right now there's not a clear answer, but what I can say mechanistically is your muscles have a lot more of those creatine transporters expressed to be able to essentially suck up that creatine and store it as phosphocreatine. Whereas your brain has a lot less. So that's why we see the numbers of 95% going to the muscles and only about 5% going to the brain because your muscles want it so much more. So the thought is that we need higher doses. We also need longer dosing durations because as I mentioned, a lot of these trials only go for 8 weeks. Is that enough for the brain? I don't know. Maybe not. So we need higher doses, longer trials to see kind of what's happening at the brain level. And another point that you brought up that was important is in a metabolically demanding state such as sleep deprivation or depression, it seems that the brain is more likely to soak up some of that creatine based on some of the, the trials that we've seen. When you're in one of these metabolically demanding states like depression, your brain is not working as it usually should. Usually the body makes energy through this fancy process called oxidative phosphorylation where you make energy or ATP, but your body's not as effective as doing that when it's it's sleep deprived or, or depressed. So what creatine is able to do is it is this essential backup system where it can replete that ATP or energy at a faster rate, but it eventually runs out because your brain only has so much creatine in it. So that's where I think that we reach those mental blocks or some of the fatigue symptoms associated with depression. So not to say that depression is creatine deficiency, but creatine may be able to help with some of those symptoms. And may help even facilitate getting into exercise or dietary patterns and things like that. So I don't think it'll necessarily be a cure for depression, but I do think it has a significant role in helping people gain that momentum and may even have a role in more of a mild depression where all you need is that little push or that extra energy boost.

You know, it's not crazy though, what you just said. Like, it's not a creatine deficiency. However, think about it. We are in this crazy time where sleep deprivation is the norm because of having all the blue lights and a lot of mental stress. And then, okay, we're exercising. Then you wonder if there's only so much creatine in your system and you're not getting— so, you know, we're making that gram a day that we can from arginine glycine methionine. Then we need to get the rest from food. But come on, who's eating you know, rare meat and fish. So then they're eating it cooked, and then some of it's going to get into nitric creatinine. So then, then you're working out hard, so that's going to increase your needs for your muscles. And if your brain's kind of getting it last, but now you're sleep deprived, under stress, focusing a lot— what if some of it was just maybe your brain's low in omega-3s and it's low in creatine? And you know, what if— I mean, you know, the research on omega-3s and depression and brain health is pretty pretty amazing. Like, what if some of this just was nutrient deficiencies?

It's important to say too, depression is a very broad term. It's one term, but it can be diagnosed in so many different ways. And not only in symptom clusters that are used to make the diagnosis, but you can have two people with the same number of symptoms, but their symptoms are so different. So you can have sleeping problems in depression, which is inherent feature of that, but what does that look like in person A versus person B? You can have low energy that can be so different in person A versus person B. I think where we go wrong in medicine is our broad definition of depression. And then we try to treat it all exactly the same. We say you've met the criteria for depression and sometimes they don't even necessarily meet the criteria for the depression, but they just have, you know, one feature, which maybe is more of just kind of a, a mild sort of presentation. But then you're given a medication or, or started on something that may be a lifelong therapy. So I think we're very quick to make these changes, but I think we need to first redefine or relook at how we conceptualize depression before we can look at how to treat it. And again, that's what circles back to the individualized care. Yeah, maybe creatine or exercise is not for everyone, but as you mentioned, a lot of people are sleep deprived. A lot of people are pretty sedentary in their life and would benefit from being able to move more or have a little bit that extra energy. So I think we need to work on personalizing our care more, but they're— in doing so, we also need to expand our, our treatment options, which are, you know, in simplistic terms, limited to antidepressants or therapy right now.

I would love to imagine a world where these, these things like moving more and eating a more well-rounded whole foods diet and having creatine and fish oil and things like that are foundational so that we're repleting any deficiencies. And then you would have your genetics and epigenetics and your lifestyle, and you'd look at all of it and be able to pinpoint. That would be, like, amazing. I know it's coming. I know it's very different than— I remember my, my son with the brain injury has had rapid cycling bipolar disorder as a child, right? We take him to a psychiatrist. Literally, this will drive you crazy. In 5 minutes, this guy goes, oh, now he is— my son just sitting there 5 minutes. He's got OCD, ODD, ADHD, and, and rapid cycling bipolar disorder. And I'm like, you didn't like I was like, what are you talking about? You know, this cocktail of things that he was going to go on. I'm like, yeah, that's what I was like, sought out Dr. Amen. I'm like, nope, we will not be doing this.

You know, and I think that's an issue in, in the medical system as a whole is just this time crunch where we're making very quick judgments based on very limited information. And, and that's where you run into problems where then you're started on a slew of treatments that may or may not be appropriate because there's, there wasn't the appropriate looking into what are these symptoms or, or beyond what are these symptoms, what is a unifying feature of these symptoms? So an example would be, you know, we, we spoke about sleep deprivation, sleep deprivation and isolation or sleeping issues. So stuff like obstructive sleep apnea where you, where, where people require to CPAP machines to sleep because their airways are closing when they're sleeping. These sleeping concerns can actually cause depression. Or cause anxiety. And if you're to look at it just from a symptoms-based perspective of what are your current symptoms? Oh, I have low energy. I'm not sleeping well. I, I, my mood is very low. You may diagnose that person with depression, but if you don't look into what is causing it, you're not doing that person a proper care because maybe fixing their sleep would do a whole lot better than prescribing antidepressant or, or even therapy in that instance, because they have a reason for feeling depressed. Or having a medical workup for someone who comes in with depression, their thyroid hormones maybe are just low. So I think these are things that are often overlooked, and it's a testament to how stressed the medical system is because the quickest thing is, here's your prescription. But I think there are a lot of factors that go into depression. Sometimes the answer is medication, but I think too often it is right now, whereas we should need to explore other avenues for treatment and also causative factors for, for the presentation.

Well, I hope you'll be out there teaching as well.

Yeah, yeah, I try my best in residency.

You know, you've got, you've got some really great information, and you're just— I mean, you're in residency and you're already with all of this information. So hopefully you will be one of those people that changes, changes the way we think about treating mental health. That's, that's my, my hope over here. What are you working on now? What's, what's the latest?

Yeah. So research-wise, my main interest has been pivoting a little bit to the creatine sort of realm cuz I've, I've had a, a big interest in that. I'm of course always doing exercise things, but I've written a few papers for creatine for depression, but we're working on mechanistic papers for other disorders. I haven't had a chance to actually dive into them. As I mentioned just yesterday, I finished writing up a paper on a rationale for higher doses needed for creatine from—

I gotta connect you with my creatine researcher because yeah. A, probably fund some stuff, but B, give you another one to look at with different pharmacokinetics because yeah, sometimes the higher doses cause other problems and people won't stick with it.

Mm-hmm. Yeah, no, I would, I would love to be able to be connected there cuz I think it's an emerging area that I'm really passionate about. And as I mentioned, we're trying to set up a few trials for creatine right now too. So the first one that I mentioned was pairing it with resistance training for depression. The second that we're trying to get funding for is using it as a monotherapy for mild depression. So, um, taking a population that's been diagnosed with depression, giving them 10 grams of creatine and seeing what happens versus a placebo. And I honestly wouldn't be surprised if we see benefits. Right now I can't say anything evidence-based to say creatine monotherapy is necessarily an appropriate treatment for mild depression, but I think this trial will be very important to say, is this something that's feasible? Because a lot of the population suffers from this mild or low-grade depression. And like I mentioned, people are very quick to be on an antidepressant, which are hard to come off of sometimes. So, I'm very interested to see the results of this, to see what that shows, because that could be a paradigm shift in terms of how we go about treating some of the milder cases of depression.

That could be. And again, I still go back to— I think, you know, as I started to unpack this, I went, I think women are mildly creatine deficient, you know, and especially as they're heading into— like, you think of perimenopause, I'm tired, I can't I'm like, you know, I'm depressed. I'm losing muscle. I can't perform. Like, like, mm, you know, like, so could be interesting. Yeah. I will connect you up with my buddy cuz he might be able to do some funding here.

That'd be great.

I know it's always the thing. I'm gonna put all of your information. I've got all of your social media sites. I'll put it all at jjvirgin.com/happyworkout is what the team decided to call it. Um, where are you most active? Which platforms?

So I'd say I'm most active on my Twitter or X. I try to post a study or breakdown there every single day, and I try my best to interact with people. I'm trying to be more active on my Instagram too with different form content. As I've been doing more podcasts, I've been trying to post—

That's a lot, isn't it?

Clips there. Yeah. I would say if, if you want to follow me anywhere, it would be the most beneficial at either X or Twitter and, and Instagram. And slowly I'll build other platforms, but for now I'm, I'm busy from the research front. But yeah, it was, it was a pleasure to be here and thank you for having me.

I appreciate it. Thank you. So a little, a little fun story. Back when Grant was in the hospital, I, as you can imagine, had some serious anxiety going on. And what I would do to manage that anxiety was I found a gym close by and I also found the hospital stairs. And I was just doing what I needed to do every single day because I found that if I didn't, I wanted to crawl out of my skin. It like just saved me from being able to just handle all that was going on. It was like, um, kind of an animal shaking off all the stress. So this can be enormously helpful for you if you are depressed, if you are anxious. It's amazing what exercise can do. And in fact, if you listen to my other podcast interview with Eric and Mietjes, where he talks about the Hadza and lessons from them, he talks about the fact that they don't really know what depression and sadness is. They said, oh yeah, if we're sad for more than a couple days, we end up getting hungry and we have to go out to, you know, hunt animals, and then the depression's over. So meaning the movement solves that. So it's amazing how many things exercise can help. Like, don't really hear about, you know, the things that it doesn't, doesn't do well. So yet another reason to make sure that you're moving more throughout the day. And remember, it all counts, even if all it is is just doing a couple exercise snacks, which we created. I'll have to just tell you this, we have a Snack Challenge at jjvirgin.com/snackchallenge. That literally just takes you through, if you have, you know, a couple minutes a day, what you can do. We call it 10 minutes to win it, to, you know, shift your physiology. So there you go. Hope you enjoyed this episode. The big takeaway from here is to just make sure you're doing a little something something every day. Just get moving and then build on that.