Is Bipolar Disorder Really a Diet Problem?

I live with bipolar disorder type 2. So I started to have for the first time, suicidal ideation.

The treatments can be helpful in mitigating some of the symptoms, but they're rarely 100% effective and they're often barely effective and they definitely don't ever cause a cure. Dr. Iain Campbell is a neuroscientist and researcher exploring the radical idea that bipolar disorder might begin not in the brain, but in the body.

I didn't realize it was a kind of form of ketogenic diet. Essentially, that's what it is. I felt like I'm thinking clearly about my life for the first time. I'm not depress, depressed, I'm not manic. If your brain can change like that and it changes who you are as a person, what does this mean about who we are? Are we just a bunch of chemicals that they're disrupted? You become a different person.

What's really interesting that you define a lot of these mental health issues and chronic disease in general, is Ian, welcome to the Dr. Hyman Show. It's really great to have you today.

Great to be here.

All the way from Edinburgh.

Yes.

University of Edinburgh.

Yes, that's right. That's great.

Last I was there, I think I was 17 years old. It was in 1977. I bet it's probably hasn't changed a whole.

I love Edinburgh. There's such a tradition of history and science there, the Royal Society and lots. There's no end to inspiration for science in Edinburgh. So I've come wearing tweed to represent my country.

I know, I noticed. I noticed you had a tweed jacket on. Listen, I think we're going to get into a topic today that I have been thinking about for a long time, and that is the whole field of psychiatry and what's wrong with it. Ever since I was in medical school and I spent a month in a psychiatric hospital, not as a patient, but as an intern and as a medical student, talking to people, listening to stories, seeing the abject failure of our mental health system to effectively treat and or cure mental illness. I mean, often the treatments can be helpful in mitigating some of the symptoms, but they're rarely 100 effective and they're often barely effective, and they're definitely don't ever cause a cure. Our whole thinking about psychiatry is so fundamentally flawed. This whole labeling of people based on their symptoms doesn't make any sense because it's not looking at the root cause or the mechanism. You know, we have so many different ways of thinking about mental illness throughout history, and we're just chit chatting a little before the podcast. And I, I talked about a book I read in college called Madness and Civilization by Michel Foucault, who is a French philosopher. And he was talking about the different interpretations of mental illness throughout human history, from visitation from the gods to possession by demons to, you know, Freud and his, you know, it and the ego and the superego and your, you know, sexual issues as a kid with mother, whatever he thought. And then there was this sort of biochemical imbalance theory. You have this biochemical imbalance and it wasn't so far off. There was some biochemistry involved, but it wasn't what they thought. So many people suffers so terribly from mental health issues. And globally it's almost a billion people. A billion people, yes. That suffer from some type of mental health issue. And it could be anything from depression to, which is. Affects about almost 4% of the global population to anxiety to bipolar, which is 1 or 2%. Schizophrenia, substance use, eating disorders, these cause so much human suffering and we've really never been able to nail it as a, as a medical profession. Now when I wrote my book the Ultra Mind Solution 2009 it was published, it was really clear to me that we were missing the boat and that I was seeing kind of smoke signals from my patients stories and from intervening with them with diet and nutrition and supplements and fixing their microbiome, dealing with environmental toxins, balancing their hormones, and a whole host of things that I would do just to get them healthy. Because functional medicine essentially is a science of creating health as a side effect. Their psychiatric problems would get better.

Yes.

And I was like, what's going on here? And that's what led me to write this book. And I called myself the Accidental Psychiatrist because I was like, I never intended to treat people's mental health issues, but whether it was schizophrenia or autism or ADHD or OCD or depression or bipolar disease, I was seeing just like remarkable results. And it made me really frustrated because no one was paying attention to this.

Yes.

And at the time there was, you know, there was some literature. It was, it was when I started to dig in and to sort of see if I could validate my clinical observations through looking at the scientific research. I was like, oh, there's. People are kind of studying this a little bit and there's something here.

And. Yes.

And in the last couple of years, it's just exploded with Chris Palmer's book and brain Energy about using a ketogenic diet. He's been on the podcast to treat schizophrenia and bipolar disease to the development of the metabolic psychiatry department at Stanford with Savanni Sethi and the Department of Nutritional Psychiatry at Harvard and now at Edinburgh. You've got a whole metabolic psychiatry research infrastructure there. That's quite amazing. We're going to talk about. So I think I'm so thrilled to have this conversation with you because so many people out there suffer and they don't need to suffer, and they suffer needlessly. We're able to apply what we know. And the problem is when most people go to their psychiatrist, they're practicing, you know, mid, you know, 1970s, 1980s medicine and not 21st century understanding of what happens in the brain. And I said this a bunch before on the podcast, a saying in medicine that neurologists pay no attention to the mind and psychiatrists pay no attention to the brain.

Yes.

And then we're going to get into this in the podcast and I'm really excited to talk about this because we haven't really covered this, which is what are the biological signals that the body gives off that can give clues about what's going on with mental health issues that we can detect through blood testing, biomarker testing, through genetics, through brain imaging. It's an incredible field, metabolomics, and we're seeing that there's a there, there. It's not just in people's head that there's actually something really going on. And your story is pretty remarkable, Ian, because, you know, you. You come with this as an academic, as a PhD from Edinburgh, as a researcher interested in this subject, but you also come at it from a personal vantage point where you yourself were suffering from a psychiatric illness. So maybe we can start by talking about your personal journey and it's actually on the very thing you're researching now. And let's kind of rewind the beginning of your journey. How was your life like before you discovered this whole field of metabolic psychiatry?

Yeah, so I definitely shared the frustrations about psychiatry, mental health treatment from a patient perspective. I live with bipolar disorder, type 2, and I'm part of a community of many bipolar patients, people living with psychiatric conditions. And unfortunately, the suicide rates are very high at the moment and there's a real lack of remission in patients. And the level of suffering in these conditions is much more than many people are aware of. They're really devastating. I lost a family member to a psychiatric condition. My mother had a severe neurological illness. And it really affects the whole family of the person and their whole network around them when you suffer from a psychiatric condition. And so we really want to See, treatments move forward. Like you say, since the 1970s, there haven't been very many new treatments in psychiatry. In other fields of medicine, there's been many iterations of new medications. And in psychiatry, there's been very few new treatments and developments in this area.

So before using metabolic therapies and ketogenic diet, my life was very chaotic because I had severe periods of depression. And I think when people hear depression, they think you feel sad or your emotions are down, but really it's like a physical state of physiological crisis in the body. These states of depression and bipolar disorder, you really. Your energy is so suppressed that you can't move, you can't think, you can't feel. It feels like you're just constantly deprived of oxygen and you're just really trying to catch your breath. And that's a much more accurate description of what bipolar depression feels like than kind of feeling sad. So I experienced those states, and then on the other side, I experience hypomanic states where you get these kind of periods of creativity and productivity. Mania becomes dysfunctional, where you have to go to hospital. But in hypomania, some people can function for periods of time. So my battle was to try and find a way to live a life where I could be severely depressed, but then have these periods of productivity and creativity for short periods. And there was really nothing that I could do. I struggled with many aspects of life to fit in this way because it was so unusualist dynamic. But I did find long before as an academic, that I could write music because I had these periods of creativity and focus. And as long as I created good music during those times, that could carry me through the rest of the year. So when I was 21, I was signed as a music producer to Universal Music. And I worked for a time for a film composer called Harry Gregson Williams. He wrote the recent Gladiator 2 score. And so I used music was the only way that I could survive at the time because I was able to use this creativity. And when I was depressed, I would disappear for months at a time and be unproductive. And so it was a very difficult life. And the thing that eventually it came to was I was working as the assistant to this composer and I would reach periods of severe depression. Everything in my life was fantastic. I had a wonderful job, I had opportunities and I enjoyed working, but I still, completely unrelated to my scenarios, we'd go through these suicidal depressions. And at one point I reached a kind of a low point where I really was not able to function. And I had kind of catatonic depression where I couldn't leave the house for almost two months. And my wife became very concerned about this because I'm normally able to kind of manage things to a certain degree. And the hardest thing with bipolar and psychiatric conditions is you feel some part of you that is, you want to contribute to the world, you want to be there for your family, you want to make something of your life, but something about your physiology doesn't allow you to do that. And it's a great conflict for people with psychiatric conditions, because the guilt and the sort of shame that comes with that and not being able to function and contribute in the way you want to can drive people to suicidal ideation. This is what I experienced, was I felt like, I can't be a good husband to my wife. I can't be a father to. I want to have children. I'm not good enough to be a father to these children. So I started to have, for the first time, suicidal ideation. And this is what drove me to try and really understand my condition, because I felt there's something not true about what I'm being told about this. I'm told it's a neurotransmitter, a chemical imbalance.

And you were taking medications and they didn't work.

Yes, yes, I took. The problem for me was that I was told, this is a chemical imbalance in the brain. It's a neurotransmitter imbalance. I even wrote music about this. This was one of the main topics I wrote music about, because I was trying to understand what this illness was. And I really had a kind of existential crisis because I couldn't live my life the way I wanted to. And I really went into these deep depressions and turned to philosophy or religion or spirituality to try and find some explanation for why would someone experience life like this? And ultimately, I didn't think the answer would be in science or biology. I thought it would be in philosophy or some of these areas. But. But really the answer for me has come through scientific understanding.

So I. I wonder, like, what happened when you started a ketogenic diet? How did you come upon this, and how did you end up using that? And what happened to you when you did in terms of your own life?

I really kind of hit a wall with illness where I kind of recognized. And this is, unfortunately, the experience of many people. I lost a member of my family to psychiatric illness and suicide. Yes. And my mother had a severe neurological condition for about 10 years. And I could see how devastating brain disorders can be for people. My mother had a brain aneurysm and for about 10 years was completely a different person to the person I grew up and known during my life. And it made me question, you know, what is the brain and who are we as people? If your brain can change like that and it changes who you are as a person, what does this mean about who we are? Are we just a bunch of chemicals that, you know, if they're disrupted, you become a different person? It doesn't feel like that. It feels like there' something more to. So these were the questions I was engaging with. And I recognized that my own brain was not working enough to live a reasonable quality of life. And I'd seen the end point of the tragedy that happens when people can't function like that. But. But people don't appreciate, I think, that it's really not a choice for people. It's like the level of suffering becomes so much that this becomes something they start to think about. So I really decided I'm going to try everything possible to survive this, mainly for my wife. My father and my mother were very supportive and help helpful to me during this time. And I wanted to do everything I could. It wasn't even really for my own life anymore. It was. I kind of recognized that I didn't have a life anymore. But I did think, I don't want this to be a tragic situation for anyone else. So I made this document and I put in. I just started listing. I started reading everything. I read every book that I could find about the brain, about mental health, about physical health. And I started listing all the interventions. I was listing all the supplements you had in Ultramaya. I was listing, you know, I was going through every book you could think of about mental health and listing everything that could be done. And then I kind of ranked them by what I thought was most likely to be helpful. And I thought it would certainly be helpful to lose weight. And I was very overweight at the time, and I thought that this would probably be somewhere to start. At least I can do that, and at least it seems possible. So I started reading about, like, how does one lose weight? And I read about the new this at the time it was sort of like the new Atkins diet. It was like a kind of. But I didn't realize it was a kind of form of ketogenic diet, but it was essentially, that's what it is. And so I just read online that people were losing weight. I wanted to try something. So I did this. And I remember sitting on the bus for the first time in many decades. My thinking became clear. It felt like the lights in my brain were kind of clicking back on. This is something that Mary Newport has described with her husband with Alzheimer's. Like there was a kind of energy returning. And I felt like I'm thinking clearly about my life for the first time. I'm not depressed, I'm not manic. And I also am appreciating things that I couldn't see before. I looked out the window and I saw a tree in the sun. And I felt this experience of happiness. And I thought, this is what most people feel like when they look at nature. They see nature and they feel this sense of calm and peace and enjoyment. And I'd never known I hadn't experienced that in such a long time that it was foreign to me. And I didn't know what was happening. I didn't have any idea at the time the diet was having any influence on this. I just knew that I was feeling well. So my father was a medical professor and I called him and I said, this happened a number of times. And I said, I don't know what's happening, but I'm becoming. Well, for periods of time I'm having wellness and I don't understand why that's happening. And so he said, well, what's different? And we worked through lots of things and I thought, I said, well, I am doing this diet and I'm losing some weight and maybe there's something happening here with the diet change. And so, you know, I was quite unfortunately, quite ignorant of these things at the time to not know that could have such an effect. But I eventually realized that this is a form of a kind of ketogenic diet, not a full ketogenic diet. But I was entering periods of ketosis and I started to measure it. So I got a blood ketometer and I started measuring sort of almost daily my blood ketones. And I realized that the times I was experiencing this kind of remission of symptoms were when my ketone levels were higher. And this really changed my entire life because I thought for the first time there's something I can do, there's something that is making a difference to my symptoms.

Incredible. Were you able to get off medication at that point?

So I currently don't take medication for my condition, but that was a long journey for me to want us to be extremely careful with coming off psychiatric medication. It's, you know, these. Your body becomes co adapted to these molecules that you're giving it and so is. So coming off medication is usually a very slow tapering with a psychiatrist, very closely working with a psychiatrist. And I think that's the best way if you are.

You know, considering this. But for me it was a very long journey and like you say, between psychiatry and neurology because, you know, Kraepelin wanted to understand this biological basis. Freud felt it was about psychoanalysis. And there was this great rift then between psychiatry and neurology. Jean Martin Charcot was one of the early psychiatrists who focused on. And a lot of people don't know this. I'll come back to Charcot, but to mention about Freud, he trained as a neurologist. He trained to study neurology and the operation of the brain and how it works. And he became disillusioned because he felt like we can't understand it through this methodology. So he went into psychoanalysis. But he was originally a neurologist and that was really ironic. Yeah, absolutely.

He took us down a path for 100 years that turned out to be quite flawed.

Yeah, absolutely. And then Jung got really interesting, his student, Carl Jung. But yeah, it was bizarre because it split off the brain and the body in a way, this kind of biological basis and this kind of psychoanalytic approach. But yeah, this really is echoed down through the ages because in our universities we have separate departments for physical and mental health. We have psychiatry as a completely isolated discipline and it doesn't have a lot of interaction with the other physical sciences. And I think that's been detrimental for mental health treatment because we've fell into these kind of paradigms of viewing this chemical imbalance so forth, instead of viewing the whole body as in a holistic sense. So I mean, you mentioned Ultramind solution and I read that back in 2016 and this was actually during the time I was living in a fifth floor flat in Edinburgh and I was really struggling with suicidal ideation at the time. And you don't want to be living in a high flat during such times. But I just started reading everything that I could on this topic and I read the Ultramind solution and the thing that struck me in it was the chapter on energy and metabolism. And at the time I wasn't doing a ketogenic diet. I wasn't aware of metabolic psychiatry at all. But it, but it struck me this thing that you said about mitochondrial function and bipolar disorder and you link to this paper by Cato. So I started really looking into this and I felt like this makes sense to me. Like it feels like an energy disorder. It Feels like I have bursts of huge amounts of energy and then I can't function for it. And it feels much more like an energy disorder than a neurotransmitter imbalance. So that really spoke to me. This was obviously ahead of its time.

It's still, I think, ahead of its time.

Yeah, absolutely. Unfortunately. Well, you said 2009, it was published, so I read it in 2016, so I was catching up, which means I.

Wrote it in 2007.

Yeah. But it is remarkable what you described in that book because it's now becoming a major research focus in, like, mainstream universities. If only we'd listened a bit earlier.

So that's powerful. And. And when you took the medications that they prescribed for you, it sounds like they. They didn't really do much for you.

So it is.

You were still having suicidal ideation, you were still depressed, you still had a hypomanic or manic episode.

I think medications can be life saving for people. In acute scenarios, when you go into hospital and you're acutely manic, then these do save people's lives in those scenarios. You know, the trials we do on medication last a very short period of time compared to the length of time that patients take them for. And the long term physical effects of some of these can be quite devastating for people's cardiometabolic health. So many of the mainstream medications for bipolar directly lead to metabolic dysfunction.

The drugs that treat like bipolar and schizophrenia are often antipsychotic drugs which cause you to overeat and get to be diabetic or insulin resistant, which is what's causing the brain dysfunction in the first place. So you're actually piling disaster upon disaster.

Yes. And it is tragic for patients because you see these young people in high school that will go on these medications and put on sort of 30 or 40 pounds, and at that age it's devastating for your self esteem. And it leads down to a trajectory where this is not being managed. It's not really the responsibility of a psychiatrist to manage physical health and it's not really the responsibility of the GP or the. That's what we call it in the uk, but the kind of primary care to manage the physical health of someone having these side effects. So it's in this middle place where nobody's really managing the side effects of these psychiatric medications. And so we're exploring kind of adjunctive and different ways of helping people to manage these.

What was it like for you to then read about mitochondrial dysfunction and then for the first time, then ended up researching it? You know, that exact thing years later, which you're doing now, when I was.

Reading it, and I do believe it was the first time that I'd heard about this when I was reading ultramind, because this was long before I knew about ketosis, ketogenic diets, metabolic psychiatry. But I read the paper you linked by Cato describing these kind of mitochondrial dynamics and bipolar. And I thought, this makes sense. This doesn't feel like just a chemical imbalance. It feels like your energy is so profoundly depressed and then elevated. So it spoke to me as a patient on that level. That's why metabolic psychiatry is gaining such momentum, because patients recognize there's something more. More about our condition that we don't yet understand. And. And this is something that speaks to our experience.

I think it's so important. And I think that, you know, you sort of mentioned this paper I linked to. I don't really remember the paper, but I do remember is that, you know, I was diagnosing people based on doing deep biomarker testing.

Yes.

So I was looking for things that other doctors don't look for. I was looking at their genetics, their genetic variations, and, yes, neurotransmitter metabolism or methylation or detoxification or other things. I was looking at their mitochondria and their function through organic acid testing, which is not something that's typically done in traditional medicine. I was looking at amino acids. I was looking at nutritional status at toxin levels. And so I would actually, I wrote the book very quickly, and then I was like, oh, I better go check and see if there's references that support what I'm saying, because I'm just writing down what I've observed. And I don't know if I'm just making this shit up or put something there. And I basically did it in a weird way. I basically backfilled the book with the scientific literature that validated the things that I was observing clinically. And in fact, Dale Bredesen, who's sort of helped develop the field of. Of Alzheimer's treatment using the same approach, had the same experience reading the book around Alzheimer's, said, well, you're talking about Alzheimer's reversal using all these concepts that I actually was studying in the laboratory that I didn't know they could be applied clinically. Take us now to. To where we are now and how you kind of entered this field of metabolic psychiatry. What is metabolic psychiatry? What does that mean? Why does it matter more in now than ever before?

So metabolic psychiatry is essentially a proposal that I know you've recognized for a long time. But there's an energy disruption, a metabolic disruption that underlies psychiatric conditions. And this metabolic disruption, this energy disruption, affects the brain. And for many people like we've described, they've been told this is a chemical imbalance, a neurotransmitter imbalance. But one of the ways I think about this, when you hear this as a patient, is it's like if you imagine you were driving down the highway and the car is filling up with smoke, there's clearly an emergency happening. But the way you address that is not necessarily to change the air conditioning. You want to look for what is causing this to happen more fundamentally. And the neurotransmitter explanation feels, as a patient and someone living with the condition, to many of us, like we're trying to adjust the air conditioning when there's something much more fundamentally wrong with our engine system. But if you address the fundamental disruption, which is the engine is on fire, your metabolism is not working, the energy production is not working, it fixes all the downstream problems. You don't have to mix with the air conditioning, you don't have to worry about smoke. You don't have to. All the things that can go wrong can stem from this more fundamental disruption. And so this is what people such as yourself, Chris Palmer, are proposing. This kind of energy disruption is the root cause of mental illness. And I think this really resonates with the patient community because it feels much closer to what we're experiencing, experiencing fixing this kind of engine versus trying to adjust, you know, very specific aspects of neurotransmission and so forth.

So basically, it's a metabolic problem. It's sort of like diabetes in the brain, in a sense. Like, it's a. It's a. And the brain is the source of, you know, so many mitochondria. It's got more mitochondria per cell than any other organ in the body. And mitochondria are the little.

Yes.

Energy factories in your cells that take oxygen and food and combust them to turn into ATP or energy. Yes. And if there's an energy crisis, because you can't make it, because there's basically bad energy.

Yes.

You're going to have a whole set of downstream symptoms and problems as a result of that. And. And for some people, it might manifest as diabetes. For some people, it manifests as schizophrenia. For some, I mean, bipolar disease or as Alzheimer's, which they call type 3 diabetes. So it's the same fundamental problem of insulin resistance and instant signaling and glucose metabolism. That's disrupted, that is, you know, can be caused by many factors. Yes, but. But you're. You're basically talking about going upstream and dealing with the root causes y the problem.

Insulin signaling is a particularly interesting example because I think some of the ways we're trying to treat mental health conditions at the moment are kind of obtusely or bluntly addressing these pathways, but they're not giving a full holistic benefit to the metabolic problem that's underlying the condition. So I have a paper in Nature Journal Translational Psychiatry called Lithium and insulin signaling, and I point out in this paper that many of the major targets of lithium are part of the insulin signaling network.

By the way, lithium is the drug that's used to treat bipolar disease.

You know, the PI cycle, GSK, 3, AKT, MTOR. These are all parts of the insulin signaling network.

For those in English, those are the biochemical pathways that relate to your blood sugar and insulin control that we have many redundancies in. And there are many of those pathways that get interrupted by problems with energy metabolism.

Since proposing this, there's been quite a number of studies on it. There was a study in Lancet Journal in your Biology, where Martin Alda, who developed the Alda Scale for Lithium, for example, and a team investigated this in.

They make these kind of organoids. They're like mini brains. They derive from neurons from bipolar patients, and they found that lithium was modulating this insulin signaling pathway. But I think what we might be starting to discover is that we're kind of obtusely or like I say bluntly addressing some of these metabolic pathways through various forms of treatment, for example, like suppressing metabolism so heavily that someone can't go manic, but they also put on 40 or 50 pounds of weight and have diabetes. And, you know, so it's like you're stopping the acute mania, which can save someone's life in hospital, but in the long run, there's this metabolic damage and dysfunction that can happen. And there's other medications like lithium, which I think address aspects of insulin signaling that can be, in the short term, helpful for someone, but in the long term can lead to damage that leads to, you know, diabetes and so forth.

Thyroid function and other things.

Yeah. So I think looking for better metabolic treatments is a really important area for psychiatry research.

So we're kind of entering this new year of psychiatry, and sadly, it's not getting to patients who need it most. Before we kind of dive into the biology, I want to really get into the biology of what's happening and the Genetics and some of the diagnostic tools, the blood biomarkers, metabolomics, functional mri, imaging, imaging. You know, the thing about psychiatrists never do brain imaging. It's kind of crazy when you think about it.

It's like, but it's like you want to, you don't want to look under the hood and see what's happening.

Someone once said that modern medicine is, is like trying to diagnose what's wrong with your car by listening to the noises it makes, you know.

Instead of lifting up the hood and looking underneath the hood. But you know, before we, we get into that, I want to sort of touch on, I think something that's really quite important, which is the field of psychiatry has, has classically been about this diagnostic manual called DSM 5, which means the Diagnostic and Statistical Manual version 5, because there's been 1, 2, 3, 4, 5.

Yes.

And, and the latest version and is basically. It's descriptive.

Yes.

It just, it's a phenomenological description of these symptoms. And if you, you, you fall into this category of these collective symptoms, you get this diagnosis, you had adhd, you get bipolar disease and there's subcategories, schizophrenia, depression, different kinds of depression. And it's very, very detailed and it's like incredibly like detailed about which type of each mental illness you can get. Different kinds of anxiety disorders, different kinds of bipolar, different. It's like, and it's fundamentally really flawed because to kind of get back to your earlier point, there's fundamental underlying biological mechanisms that are causing people to suffer with these problems. Yes. And unless we take seriously this fact and take seriously the research that we need to under undertake to actually investigate these things, we're never going to help address one of the biggest causes of suffering globally. I mean, yes, obesity, diabetes and heart disease, cancer are really the big killers, but when you look at them, they're also metabolic problems. And when you look at the, the amount of quality of life lost that we call it the, you know, quality adjusted life years or qualities, basically, how many years have you lost to suffering? Which you lost many years to suffering. When you take that number, you know, depression and psychiatric illness far exceeds everything else.

Yes.

And so this is like a global crisis. And, and I don't see really, except at the margins, a lot of work being done around this. You mentioned the Brzezinski Group, which is a group of, of, of that sort of help fund a lot of this work only because of luck. Did someone who was very wealthy have a kid who was bipolar, who went keto, who Got better. Who said, what's going on here? Let me start throwing millions and millions of dollars at funding this research because it's not happening from the academic medical centers really much. It's not happening from NIH very much. It's like maybe a little here and there, and it's starting to change. But I think, I think we have this really fundamental diagnostic flaw. And, and I think what's really exciting to me is that it's not just me and my little clinic treating patients, seeing these things. It's now academic scientists starting to kind of dig in and see these problems. So what, what are the kind of novel and emerging diagnostic tools that we are using to start to map out what is going on with these people? And, and by the way, the whole idea that there's like one cause of depression or one cause of bipolar disease, or one cause of schizophrenia or one cause of autism or whatever it is. Yes. Kind of misses the fact that we're all unique and different.

Yes.

And that different people have different combinations of things that need to be treated. And so while they have some common themes, you need to sort of look at the underlying individuality of each person and begin to understand how to unravel that accordion knot.

So, I mean, I can answer it from a researcher perspective and a patient perspective. So you mentioned the Buzouki family, who funding metabolic psychiatry research, and Matt Bouzicki, their son, received a diagnosis of bipolar disorder. And, you know, he had really incredibly severe symptoms. He was hospitalized many times, went through, and their family really went through, you know, many treatments, like over 30 treatments. Having full access to the US healthcare system and even being able to try every treatment available. Nothing was helping his symptoms, even as people who had ability to do that. So you can imagine what it's like for homeless people, for example, people that it's very difficult for people, even if you can try everything, to have any effective treatment and treatment resistant patients. And eventually he went on a ketogenic diet with Chris Palmer, Denise Potter dietitian, and experienced remission of his symptoms. And in a kind of parallel journey, my father and I were researching this and trying to understand how do we get research to happen to address this.

And your father's a researcher as well?

Yes, he worked in developing countries doing global health research throughout his career. And he's always been interested in. He basically saved my life by helping me through bipolar disorder throughout my life. He's a really remarkable person. And so we really were trying from the research side to understand this. And Matt and his family from the patient side were trying to understand this. And it was very hard to get any funding to understand or research this. I had to work at a day job for many years to support my research. I was turned down from every fellowship, every grant, every possible way of doing this. And I was publishing papers, but there was no interest in it. So eventually I met Jan and Matt Pizzicki because one of the few things I could do at the time was put up a YouTube video. I put up this 45 minute YouTube video describing some of the things you're describing about the frustration with diagnosis. And, and I think what we both recognized from either side was that we've been given this label that's bipolar disorder, but underlying that is a biological condition that is running that we don't fully understand. And the explanations we're being given aren't the map is not matching the territory. We're trying to describe this complex biology, but the maps we're being given for that don't fit the territory accurately. And so this was the genesis of this research, was from the patient side, from research side to.

Jan Bouzicki and Dave Bozicki funded our pilot study at Edinburgh. And this was after about six years of trying to find support for this. And this really was how the field started, through the support of the Bouzouki's putting investment because of their son's journey. And so I really find that remarkable how much they've got sort of in the trenches with patients and said, we're going to make this happen. We're going to find out what's going on here. And that is an incredibly fortunate thing to have in the world because there's not a lot of mainstream support for these ideas. But it really came from just reaching a peak of suffering. Both their family journey, our research journey, my family and many others across the world, Shabani Sethi, Chris Palmer, that have been working in this field for a long time, GA EAD treating patients and everyone sort of realizing we have to fix this, this can't continue. So I totally agree. The map is not matching the territory. And this is. We're all trying to. To reconfigure this.

Yeah. I don't know if you just came up with that, but that was something my professor mentor, Dr. Sidney Baker taught us, which is that we're given the wrong map for the territory of illness we're in.

Yes. Yeah.

You know, and something I often talk about with functional medicine is a different map.

Yes.

So how do you, if you're given a map for, you know, London and you're in New Delhi, it's not going to help you.

Yes.

You know, and I think that's what we have in medicine. We have the wrong map. And across all of all of the chronic health diseases, not just psychiatric illness, and all these diseases of chronic suffering that humanity's got right now, which is globally just so incredible. And it's only in the last 150 years that we've really begun to see the explosion of these chronic illnesses. We now begin to finally understand them. And it seems to me like a new kind of golden era of medicine and also particularly psychiatry. Now I want to sort of get into the weeds a little bit because I think, you know, as people listening often say, you know, just because, you know the name of your disease, it doesn't mean you know what's wrong with you, because you can say, well, I have bipolar, I have depression. But, like, what is unique to you? How do we sort of start to think differently about diagnosing people and using our seeing tools, which we didn't even have necessarily, you know, 50 years ago, like, we've decoded our whole genome. What does that tell us about our mental health issues? And so I think we have this moment where we can start to interrogate people's biology in ways we never had the capacity before. We can do your whole genome. We can see all your 20,000 genes, but we can see your 5 to 7 million variations in that genetic code. We can look at your metabolome, which is thousands and tens of thousands of metabolites. We can look at blood biomarkers. We can look at your microbiome, which plays a big role in mental health. You can look at your entire profile of.

MRI imaging, which is basically now allowing us to look at functional capacity, not just structurally. Do you have a tumor? But, like, what's your brain doing in a functional way? And what does that tell us about what's happening energetically in the brain?

Yes.

You know, Suzanne Goh from Harvard Oxford, trained physician, pediatric neurologist, has done a lot of work on autism and also found it to be a mitochondrial energy deficit and treated those kids with mitochondrial therapies. And they work.

Yeah. Yeah.

So I guess the question I have for you, Ian, is before we dive into the details of the biology, is people's, well, I don't have bipolar disease. I have anxiety or I have depression, or I have, you know, you name it, ocd. Do these share common things? Does this apply also to those from your perspective?

I think bipolar disorder is an Extreme version, you know, it's in 1, 2% of the population. But I think it indicates an underlying dynamic that's present in many people. And perhaps by understanding the extreme case, it could be helpful to people who are experiencing lesser symptoms. You know, seasonal affective disorder, depression, anxiety. Bipolar has very severe swings to mania and depression. But I think these happen in a lower level and a different way in many different types of people. I could share some of what the history of the biomarkers and the ways people have conceptualized bipolar and then bring it around to how this might apply to other people. If you look before the age of psychopharmacology, there was this psychiatrist called emil Kriplin. In 1921, he published a paper called Manic Depressive Insanity. And he was considered the founder of modern psychiatry. And all he did was observe his patients very closely and try to understand really what is their condition by asking what are they really experiencing? And this was long before we conceptualized this as neurotransmitters and different types of treatment. He was really just looking at what patients are experiencing, which is my interest as a patient as well. And he noted three core features that were particularly notable about bipolar disorder. And again, I think these relate to many conditions. And he said, there's a metabolic disturbance. He said, all my observations indicate that in bipolar, manic depressive insanity patients, metabolic disorders must take place. And then he noticed this.

And what do you mean by metabolic disorder?

So he would track their body weight, and he would track lots of different metabolic measures that were available at the time. And you can see in this manuscript in 1921, he's drawing diagrams, really detailed diagrams of body weight and how it changes with mood and symptoms. And so he said there's something metabolic about this illness. And then the second thing he said was that there's circadian and sleep disruption. And he said that the most striking disorders in a manic depreciative insanity are the disorders of sleep and general nourishment. And then the third thing he pointed out was that there was seasonal variation of symptoms. So he describes it kind of poetically. He said, in many of my patients, I saw Mooninus set in the autumn and Passover in the spring when the SAP shoots in the trees. And he was describing that there's a seasonal variation to this condition and seasonal affective disorder and many other conditions, schizophrenia and so forth, have this kind of seasonal variation. And so he was taking these as three core aspects of bipolar disorder. And then from there. The reason I think this is interesting is because the seasonal variation of symptoms in bipolar is a seasonal variation in energy. So if you speak to bipolar patients, in the spring, they have this huge surge of energy and activity. They want to move, they want to go out, they want to exercise, start new projects. This kind of mania really comes on strongly in the spring, but it also occurs in the autumn. And this is because the photoperiod, the length of daylight, changes very rapidly at these times. It's called the equinox, the spring equinox, the autumn equinox. And if you look at systematic review of when mania occurs in patients by hospitalizations, it occurs at the spring equinox, at the autumn equinox, and conversely, depression happens in the winter. So the same systematic review highlights winter depression. And it occurs around the weeks of the winter solstice, when photoperiod is at its lowest, lowest. So what we're kind of seeing is Emil Kirkland was describing this seasonal variation of energy and metabolism related to circadian function. And if you look at the natural world, this is a part of the natural world. Humans, for 95% of our time on Earth were living in a natural daylight cycle, seasonal variation. And it was essential for survival to be able to allocate your energy optimally. So in the spring, when there was opportunities for hunting, reproduction, so forth, it would make sense to have a surge of energy. And in the winter, it made sense to conserve energy because there's not the same opportunities available. There's extreme examples in the natural amount of food, right? Yeah, exactly, yeah. And so the extreme examples in the natural world are hibernation, torpor in the winter and migration, hyper metabolic behaviors in the spring. But these mechanisms, the circadian and metabolic mechanisms that do this energy modulation throughout the seasons are, are conserved in humans. I have a paper about this called metabolic plasticity. And I think that this is a metabolic energy and circadian regulation disorder. And I think that what it is, the underlying mechanisms, circadian and metabolic mechanisms, are sort of ancient preserved mechanisms of seasonal adaptation and metabolism. And so I think that, I know you've talked about this yourself, these kind of like ancient survival mechanisms, they become dysregulated in our modern environment. A kind of mechanism that could give you optimal energy use throughout the year, could be completely dysregulated by artificial light conditions, metabolic factors, diet and so forth. I think that, you know, we're talking about insulin signaling. And in the winter, many species suppress their insulin signaling and glucose metabolism. They go into metabolic depression.

Like bears. They hibernate.

Yeah.

And they gain all the weight in the fall, and then they. Yes, and live off the fat in the winter.

Right, yeah. And they do two things. They suppress their circadian rhythm and they suppress their metabolism. And this is what happens in bipolar depression. Your circadian rhythm suppressed, your metabolism depressed. Obviously, this is just analogy, it's not a direct comparison, but the same mechanisms underlying these seasonal adaptations are conserved in humans. Mtor, ampk, sirtuins, akt, the insulin signaling network. There may be an evolutionary mismatch we're experiencing in some of these conditions where we have these ancient survival mechanisms that our modern world is heavily dysregulating.

The light bulb in the advent of refined sugars and starches led to a big host of chronic disease problems, including mental health.

A really great example I could share is. So I mentioned Matt Buzzucki and we have a podcast where we interview patients about their symptoms. And many people have described to us, including himself, that this mania occurs around the time of the changing photoperiod, changing length of daylight at the spring equinox. And it's really notable. It's at the spring equinox, manic patients become hyper metabolic. They're going out, trying to start new things, exercise and so forth. And there's a really interesting analogy in the natural world called zagonru, which is a thing that Johann Andreas Neumann noted in Animals in Captivity. Many, particularly migratory birds, for example, around the spring equinox become hyper metabolic. They start trying to bang their head off the side of the cage, they're staying up all night, their circadian rhythm is suppressed, they're having insomnia, they're getting this deep evolutionary impulse and drive that they can't express in the unnatural environment. And it's to migrate at the spring equinox. It happens also at the autumn equinox, this behavior. So I think these are just analogies from the natural world. Of course, they're not directly related, but I think there's clear evolutionary mechanisms, circadian and metabolic mechanisms that are active in bipolar and across some of these psychiatric conditions that we need to explore.

Historically, mental illness has really been about philosophy and religion and just psychological explanations which don't actually fit the current understanding of mental health issues.

Yeah. And I think what you're saying about these philosophical assumptions about mental health, they really inform the treatment of patients and how they experience the condition. So this kind of Cartesian idea that the body and the brain are separate has really informed a lot of psychiatric practice. Emil Kraeplin, who was considered the founder of modern psychiatry, in 1921, he wrote books describing this biological basis of mental illness. But there was a kind of split in psychiatry where Emil Kruppman was looking for what you're describing, this biological basis biomarkers. But then other people like Freud were saying, no, it's to do with psychoanalysis, like you say, and issues with your mother and so forth.

Just lay on the couch for five days a week for 20 years and you might feel better.

Yeah, exactly.

You might feel better.

Yes.

Now you're getting into the biology a little bit. And so you get through the history of how we began to observe these phenomena, but they were kind of neglected. It was thought to be sort of psyche psychological in nature, or maybe it was a chemical imbalance. And I mean, the chemical imbalance idea wasn't exactly wrong. It is, it is biochemical, but it's just they were looking at the wrong thing. I was like, serotonin, it's dopamine, it's this and that.

Yeah.

And I think, you know, the genetics are really interesting around this. And there's actually whole, you know, genetic profiles. We do in our clinic at the Ultra Wellness center, look at the risk factors for psychiatric. Can you talk about some of those genetics?

Bipolar disorder and many psychiatric conditions are quite polygenic, which means that there's not any kind of core gene that can be absolutely identified to cause this condition, like with rare genetic disorders. But there are a combination of genes that contribute to the condition. And I think where it gets interesting is the gene environment interaction. You know, maybe there's an evolutionary. Many people have hypothesized as an evolutionary purpose for things like bipolar, it stays at 1 or 2% in the population consistently. Why would this be conserved in humans? Why wouldn't it be selected out of the gene pool? And many people have said maybe there was some adaptive advantage to this back in our evolutionary history when we were living in natural daylight seasonal cycles. And to have this ability to upregulate your energy so much at times of opportunity and to heavily suppress it to conserve energy at times of disadvantage would have been a beneficial survival trait. And so I think that this, you know, there might be evolutionary perspectives that can explain this genetic preservation of bipolar, but it's not one gene, it's. It's a combination, Many, many combination genes.

Yeah, I mean, when you look at the literature, there's some interesting genes that affect mental health, like methylation genes, which involves how we kind of transfer carbon and 3 hydrogen chemical group called methyl group, which is basically the currency of our biology. It's, it's involved in Everything from neurotransmitter formation to energy production to detoxification and to regulating oxidative stress and inflammation. I mean, and what's really interesting that unifying a lot of these mental health issues and chronic disease in general is inflammation. And so what happens is the brain gets inflamed. And it gets inflamed because it can handle the load of the stress from our diet in terms of processed refined carbs and sugars. It can handle the environmental toxins that we're exposed to. It can handle the various kinds of stressors. And so we, we kind of break down and there's you know, and like genes like MTHFR and COMT that you can measure now that can tell you what's going on. There's genes that relate to serotonin metabolism to, even to circadian rhythms and clocks and, and how those relate to mood disorders. So I think those are really interesting. And there's like a lot of circuit stuff. I don't know if you want to say something about the genetics.

Well, I want to ask you which circadian genes have been noted that you're interested in?

There's something called clock genes and art arntl or artful genes. These are genes that just affect circadian rhythm. They affect, yes, you know, our biology in ways that affect mood disruption if their circadian rhythms disrupted.

That's really interesting because half of my research is on, well, the majority of my research is on metabolic psychiatry, but we also have a lot of chronopsychiatry research led by Professor Daniel Smith in our Edinburgh. And the central focus of chronopsychiatry research is the things you're mentioning. Clock BMAL1 purr cry and these are your circadian regulators and they basically take signals from the environment, the light, and they convert this in the suprachiasmatic nucleus of the brain, which is kind of like a clock system in the brain. And they use that to regulate your metabolism. So this happens daily when you go to sleep. These clock genes tell your body it's time to downregulate metabolism and go to sleep, but it also happens seasonally. These clock genes tell your body about the changing light conditions, the changing length of daylight, and they then feed into your metabolic system to tell you whether to have more or less energy, to kind of conserve and, and utilize energy accordingly. So I think these make sense in terms of an energy metabolic disorder. These clock genes that you mentioned. Clock B1 yeah.

And there's also blood biomarkers. You know, I'm curious what Kinds of things you're looking at in your research and what you see in the literature around things that people can measure in their. Not metabolomics, but just like common blood biomarkers that affect mental health.

You know, on the circadian side, it's clear these clock and mechanisms feed into bipolar. And on the metabolic side, we use sort of metabolomics to try and understand this. We use this in our palate study, which I can talk more about in a minute. But we use metabolomics to try and understand what are the differences between a bipolar person and a normal person in terms of their metabolic function. And the things that we see again are these kind of insulin signaling type mechanisms, the phosphatidylinositol cycle, AKT mtor. And these are the kind of differences in bipolar patients in these metabolic signaling networks. And again, they're kind of related to energy allocation and conservation. And I think that. So in our pilot study of a ketogenic diet, one of the ones we were particularly interested in was lactate. In psychiatric wards throughout the 1970s, psychiatrists were noting that bipolar patients were having elevated lactate. I was just at a symposium yesterday in Toronto with an Andreja who studies mitochondrial function, and she's been looking at lactate as a marker of mental health symptoms, and it's a marker of mitochondrial dysfunction. Essentially, when the mitochondria aren't producing energy efficiently, they have this kind of output. I think you described it in one of your breaks as maybe an exhaust fume or something, these kind of byproducts of metabolism.

Well, I mean, you think about it when you have lactic acid build up in your muscles from exercising and you feel that soreness and then cramping in your brain, you don't have pain, but you have mental illness.

Yes, that's what it feels like. It feels like exhaustion. It feels like you've been running in a marathon and you're just paused in that state continually. Yeah, yeah, that's what I was trying to describe when I was trying to describe this kind of physiological crisis. It feels like exhaustion. It feels like when you're running a marathon, but being paused in that state of exhaustion indefinitely. And lactate is a kind of marker that makes sense in that context.

Those are sort of metabolomic biomarkers. But I want to sort of talk about some of the other things metabolomically that you can look at that have been linked to amino acids that you can measure. Short chain fatty acids come from the microbiome that modulate inflammation. There are also Organic acids that we measure in functional medicine. We've been doing for decades.

Yes.

Which measure various metabolites like kinuric acid and quinolinic acid, which.

Yes.

Are metabolites of, you know, serotonin metabolites. And, and they, they're neurotoxic and so they're, they're often linked to inflammation. So when I see a patient with a high level of this. And I would see really high levels of these.

Yeah.

In autistic patients or psychiat. Your patients are like, wow. And it would just tell me that there was, there was inflammation in the brain that was causing an interruption in the normal production of neurotransmitters.

Yes.

And. And that's been linked to depression, schizophrenia, to autism.

Yes.

Lactate you mentioned and peruvate, which are energy metabolic dysfunctions. He doesn't. Bipolar disorder. Carnitine, which is, has to do with the production of. Of and burning of fat, which is often impaired. And you see this in autism and schizophrenia. Oxidative stress or. And often these. I'm coming back to these autistic kids. But like any, Anybody with severe psychiatric illness, whether it was schizophrenia or bipolar disease that I saw, and I saw these patients in my practice, even though I wasn't a psychiatrist, because they were desperate looking for something.

Yeah. Yes.

And. And, you know, have, you know, glutathione depletion, oxy, Oxy stress markers, markers of microbial metabolism. I would see often in people with really significant psychiatric illness, like OCD or, or kids with behavioral disorders, really high, high, high levels of metabolites from bad bugs in their guts, in their blood or in their urine. And so these are kinds of things you can start to look at. They're not typically part of what you regularly can get at your doctor's office.

Yes.

But it will be soon. And this is the whole field of metabolomics.

Yes.

Essentially looking the sum total of all the metabolites in your blood. There's, you know, maybe you get your doctor annual visit, you get 19 blood tests. We're talking about thousands and thousands. 6, 10,000 blood biomarkers that you can check.

I went on a long journey with this because I was trying to understand is there anything I mentioned making this document and having everything possible I could try. And when I read your chapter on energy and metabolism, you'd listed coenzyme Q10 and various things that you can try for this. And I was meticulous. I went through every single thing and I put them in this spreadsheet and I'd order them. I would try coenzyme Q10, I tried carnitine, all the things. And I felt like this should be easier. There should be clear advice on this in mental health treatment. So I think you were describing this way ahead of its time. What we're now coming to is seeing that these kind of mitochondrial markers, energy markers, are the things we should be measuring in patients and we should be looking to improve them. And we saw this in our pilot study. We saw significant reductions in blood lactate on a ketogenic diet in bipolar patients. And this has been a marker for many decades in psychiatry that's been of interest. And we saw it move in these patients and share more.

It's funny that you're talking about like in the 70s, they're measuring lactate levels, which is interesting because it never found its way into traditional psychiatry, into regular practice.

Yes, no.

And there's also a lot of things you're talking about this energy problem in the brain. And Chris Palmer talks about brain, his book Brain Energy. And my friends Casey and Kelly Means wrote a book called Good Energy. It's all about our metabolic crisis, which is affecting both our weight and yes. Diabetes, as well as our brain health and, and, and, and our psychiatric kind of illnesses. And the secondary consequence of these is inflammation. But yes, you can measure things like insulin resistance in the body by simple blood tests. You know, this is really why I co founded Function Health.

Yes.

Where you can get access to over 110 initial biomarkers. Then you can add on all kinds of other things. If you want to study a lot of the things that need to be looked at, like insulin, like nobody checks fasting insulin. Right. But you can now measure through sophisticated tests which, which are not that expensive. We can offer through function. Looking at insulin resistance, you can look at cellular insulin resistance by measuring C peptide and insulin. Or you can look at your, just your cholesterol profile. Look at triglycerides and hdl, which is an indicator of poor metabolic health. Or in looking at your, your nutrient levels, which is really important, like homocysteine, which measures the B vitamins and vitamin D and B12, folate. These are really important. And then the inflammatory markers like CRP and, and yes, IL6, TNF alpha, these are, these are biomarkers you can measure in a regular lab test. And even things like thyroid, cortisol, iron, all these play a role in affecting our cognitive function and mental health. It should be pretty carefully looked at. And again, most of these things are available through your basic function panel or add Ons that you can add on and they should be the standard of care, but people aren't getting it. Which is really kind of why I'm like, I'm sick of doctors not doing this. I'm going to start co found a company that can let people find out about this information and take advantage of it. Not like you had to do figuring out on your own and suffering for years and years without any help.

Well, yeah, I wanted to thank you because you mentioned measuring insulin resistance in one of your patients who had a mental health condition and this kind of indicating you could improve something. And I really think that one of the best things that could happen in psychiatry is to start measuring that in mental health patients. The homa ir, the insulin resistance marker, because it's not perfect. No one measure is going to solve everything. But at least to get a kind of signal of metabolic health from people would be really helpful. And I'm trying every which way to campaign for this to be a marker that people should look at is markers of insulin resistance in patients because we know that those markers predict onset of psychiatric illness. In large big data studies, we can see that insulin resistance in early life is a marker that predicts future onset of psychiatric conditions. And it also means that people have more severe progression of psychiatric conditions. So if we could get mental health measuring like you described in this patient, markers of insulin resistance, this would be a real help.

I mean, that's terrifying considering like 1 in 4 teenagers has pre diabetes or type 2 diabetes. And maybe if you expand the definition of how we define it, which I think is way too narrow, it misses a lot of people have metabolic dysfunction. Yeah, you're probably talking about like 1 and 2. I mean, 40% of kids are overweight. Almost every single one of those has some metabolic dysfunction. Yes, it's, that's some degree of insulin resistance. And you know, you mentioned something called homa ir, which is a, is a calculation that we make to kind of indirectly measure insulin resistance. Yes, I used to do a test, it was called the glucose tolerance test with insulin where you drink the equivalent of two Coca Colas and then measure your fasting blood sugar and fasting insulin and then one and two hour insulin and blood sugar. Most doctors just measure blood sugar. Now there's a test you should know about which has just been developed through Quest that uses max spectrometry, which is a kind of a more sophisticated way of measuring blood analytes that measures C peptide, which is a precursor for insulin and insulin and gives you a ratio and it's as specific and predictive of insulin resistance as the more very invasive test that you do for research called the EU glycemic clamp test. So it's kind of an amazing new advance. And through Function Health, we offer this. I think we're the only people actually doing this now. And we're seeing, you know, significant issues with this, with this test and the degree of insulin resistance that people have. So I think, you know, you. You sort of look at the energy crisis and it really comes down to this, this fuel partitioning problem and lackability to actually get energy, make energy. Because when you're even in the midst of plenty of sugar and starch and fuel.

Yes.

Which we have an abundance of in Western society, we're still in an energy crisis. So it's like people are like, what do you mean? I'm, like, eating plenty of food. I'm eating, like, a lot of sugar and carbs. Why do I have an energy crisis? It's because at a cellular level, you've kind of busted your. Your cellular machinery that actually runs your metabolism, and that leads to this catastrophic problem which, you know, some people shows up as type 2 diabetes and some people shows up as schizophrenia, and some shows up as bipolar disease or depression or, you know, a million other psychiatric illnesses.

I was watching your interview with Andrew Huberman, the recent one. I remember at the end you said this, that these kind of like ancient survival mechanisms that kind of were thinking along the same lines of the, you know, they regulate your metabolism, and that this is kind of at the root of, you know, what this dysfunction is. And I think this makes sense in terms of mental illness, because in 95% of our time on Earth, we're living in these conditions of scarcity. And you can store about 2,000 calories of glycogen as sugar in your body, but you can store well in excess of 100,000 calories as fat. So it would be very important.

Glycogen is a storage form of carbs.

Yes, exactly.

And the storage form of fat. Well, is the fat you see in your belly.

Yes, yes. And so it would be a survival advantage to be able to switch efficiently between these fuel sources, and particularly seasonally. You gave the example of hibernation, and bears, for example, they go into this. There's some really interesting information about this by someone called Brad Marshall. He has a YouTube channel describing this. But bears will go into periods of hibernation where they'll burn their body fat and they're going to ketosis for long periods. And so you're switching from this 2,000 calorie fuel source to 100,000 calorie fuel source.

And bears go from honey to keto.

Yeah, absolutely. If only that was possible for me. I guess some people do that, but. Yeah, but, you know, when we're talking about these seasonal variations, energy and metabolism, the most pronounced seasonal change is the switch between glucose metabolism and fatty acid, keto metabolism. That happens throughout all of nature, the natural environment. And maybe, you know, when bipolar people in the winter are getting depressed and their metabolism suppressed, their circadian rhythm suppressed, they're going to this energy conservation type of mode. Maybe their body's expecting ketosis like the natural world intended. And you continue eating refined carbohydrates. Carbohydrates and sugars, which just throws these systems into chaos because they're trying to suppress your metabolic function to conserve energy and survive, but you're throwing sugar continually to it instead of giving ketones, which are the evolutionary consistent adaptation that the body is. And to me, that's what ketosis felt like. When I describe, like being on the bus. It felt like I was receiving something I'd always been looking for. I was like this. This feeling is what I've always wanted to feel, is to feel normal, to feel balanced, to feel stable. And maybe we're bringing back some of these ancient evolutionary mechanisms to people and this is what's helping them in metabolic psychiatry treatment.

Yeah. And that's true. And I think, you know, just for people listening, there are certain people who really do benefit from being on keto long term. But most of us throughout evolution have gone back and forth between keto and carb metabolism, between burning fat and burning carbs.

Yes.

Your body's like a hybrid car. Right. You can burn gas, you can run electric.

Yes.

And so that's kind of. We've lost that metabolic flexibility.

Yes.

And we get our broken metabolism struggling to continue to run off of sugar. When you beat it to death with too much sugar, that basically leads to this catastrophic downstream consequence, at least everything from mental health issues to Alzheimer's to cancer.

Yes.

To heart disease, to diabetes, a fatty liver. I mean, the list goes on and on, on.

Yes.

And so what people need to understand is that, you know, everybody needs to sort of figure out what's right for them. But learning what's going on in your own biology through blood testing now and biomarker testing, or if you do a functionality as possible.

Yes.

And you can find out if you have some of these issues, even if your doctor doesn't know how to test for them or look at them. And yes, the less than 1% of all diagnostic tests done in America measure insulin, you know, or even measure the proper cholesterol profile, which can tell you if you have a more metabolically driven cholesterol abnormalities, such as large number of lipid particles of LDL and small particles, which we can now measure. I want to sort of loop back a little bit after talking about some of the blood biomarkers and metabolomics, and we're going to be continuing to look for these using AI machine learning to have a really deep understanding of what are the patterns in the data. And I know your institute at University of Edinburgh is actually examining these things using deep, deep analytics that we can now glean through looking at millions of genetic variations, tens of thousands of blood metabolites, looking at things that we never could understand before. We can start to kind of peer into the, into the, into the mind in a way we never had the capacity to. So as we're starting to think about looking into the mind, talk to us about imaging. Because most people think, you know, if I have a mental health issue, I don't need an mri.

Yes.

But like, tell us about the idea of functional MRIs. What are those? And what are the kinds of things you're seeing in people with various mental health issues with functional MRI brain imaging?

So it's like you say, when you want to look under the hood, wouldn't you want to look in the brain when you're addressing psychiatric symptoms? But that's not been the approach of psychiatry generally. It's been very separate from neuroscience. And because of this rift between Freud and Kraepelin and so forth, we've not been looking into the brain function through imaging and through these techniques that we have available. And now that we have these, we can look in the brain and see how is metabolism working, how is blood flow, so forth. And I actually did this myself. I went and got a private MRI scan because I was like, I want to understand if there's something wrong in my brain. Is there a brain in there? My wife was joking, like, maybe did they find something?

I was reassured, but I thought there must be something physically wrong with my brain because it's so hard to live, it's so hard to function, to work. But then I got a brain scan and they couldn't find anything because they're.

Looking at the structure, not the function.

Yeah, absolutely. And so they said, it looks normal, like everything seems to be there, and thankfully it's okay. But then it left Me thinking, but no, my life is very painful and chaotic and I need to understand why that is happening. And so I think, like you say, the structural imaging has not been as helpful necessarily in the psychiatric conditions. But the metabolic imaging measuring metabolites has been really interesting and it continues to become more interesting. So the first thing that you see in brain imaging with epilepsy, bipolar, some of the psychiatric conditions, is elevated brain glutamate. This is something you've talked about for a long time, but it really, unfortunately, it's only becoming a kind of research trajectory now in psychiatry, this elevated glutamate is contributing to excitability in the brain. Hyperexcitability in the brain.

Glutamate?

Yes.

In American English, it's called yes, oh, yes, sir. Because you're like, what did he say? It took me a minute to actually realize what you were saying.

We can't pronounce consonants in Scotland. We only have vowels.

Is.

An amino acid derivative?

Yes. And so you see this in epilepsy, you see this in bipolar, you see this in schizophrenia. And we did this pilot study, the one that I mentioned, funded by Jan Bozicki. And so we looked at brain imaging to see what changes on a ketogenic diet in people with bipolar. And one of the remarkable findings we saw is that brain glutamate came down in these patients and this is something they measure in response, like anti seizure medication. A ketogenic diet was originally an anti seizure treatment. Mayo Clinic in 1921 developed it for epilepsy, where there's elevated glutamate excitatory activity in the brain.

It was also the treatment for type 1 diabetes back in the day. And Jocelyn, in the 1900s and early in the early 20s. Before insulin was developed.

Yes, of course, even before, like the epilepsy application. And I think, as far as I understand it, they saw some of the diabetes patients having seizure remission. And so that's how they started looking at its effects on the brain. But there's modern researchers now. Mark Fry at Mayo Clinic is now launching a large $3 million ketogenic trial funded by Bouzoukis to go back and revisit this for mental health conditions. Just to give a little bit of context for why glutamate is interesting in bipolar. Bipolar, the.

Elevated glutamate in systematic review is a major feature of bipolar and epilepsy. And reduction of glutamate is considered a marker of response to treatment. And the epilepsy treatments are things like lamotrigine, valparate, carbamazepine These are used for bipolar disease. These are all used for bipolar? Yeah, absolutely. And so many of our treatments for bipolar came from epilepsy. And now we're seeing this other epilepsy treatment, ketogenic diet. Many patients reporting remission or reduction of symptoms, pilot trials, case studies. Chris Palmer has been publishing case studies about this for many years. Georgia Eads published a large retrospective analysis, Shibani Sethi, using our clinic, many, many patients reporting online. I mean I document about164, about seven years ago and now it's many thousands of patients reporting effects of ketosis. And so I think when you see this anti seizure treatment that is affecting glutamate in the brain, like with the medications, maybe this is another treatment that will come over to bipolar in psychiatry from the epileps field. So in the patients in our pallet trial, we saw significant reductions in brain glutamate. About 10, about 11 to 13% reductions.

And you can see this on functional MRI. Brain imaging test, yes.

MRI, yes. And so this was magnetic resonance spectroscopy looking at metabolites that change in the brain. We looked at many, but glutamate was the most significantly changed. And the reduction we saw was about like I say 11 to 13%. And the reductions you typically see in like three months, for example, on lamotrigine might be like 6%, but we were seeing much larger reductions in six to eight weeks of a ketogenic diet. So this is really interesting because this is a real central marker for epilepsy. This is an epilepsy treatment. We have epilepsy treatments in bipolar. So we're seeing both the treatment modalities and the markers translating.

Who knew that diet could treat disease?

Yeah, exactly.

What a revolutionary idea.

I mean, it's moving. I mean to be clear, this is only a pilot study. It's 20 patients. We can't draw any definitive conclusion. But it is an interesting kind of avenue forward, I feel.

Glutamate is a very excitatory neurotransmitter.

Yes.

It's also the target of treatment in Alzheimer's.

Yes.

And again, Alzheimer's is an inflammation of the brain. So all these are inflammatory problems that show up in different ways in different people. And you see see pretty increased levels of glutamate. We all see other things. You see, you know, changes in, in connectivity in the frontal cortex. And the default mode network gets hyperactive, the amygdala gets hyperactive in a lot of these diseases. So you get basically parts of the brain that should not be Overactive are overactive. And things that are should be active, like, you know, your frontal cortex are.

Yes.

Reduced in their function. It's pretty amazing when you see these trials, like even using things like intranasal insulin for depression and cognitive.

Yes.

Impairment, Right?

Yeah, absolutely. It's so interesting how changing the metabolism in the brain can fix all these neurotransmitter issues potentially as well, like fixing the car engine and everything else sorts itself out versus trying to address all the individual neurotransmitters or symptoms. The glutamate story is one of the most interesting because a lot of the mental health research is focused on serotonin, for example, like serotonin take inhibitors. But glutamate is by far the most abundant neurotransmitter in the brain. It's in millimolar concentrations, and many of the other monoamines are only in micromolar concentrations. And so it's a really abundant neurotransmitter. And the kind of estimates are that maybe 80% of brain energy is dedicated to this glutamatergic neurotransmission. So in terms of brain energy metabolism, like Chris Palmer talks about, about glutamate, is contributing to a significant amount of what brain energy is being used for. And it's really much more abundant than the other neurotransmitters. But the trouble is, people have tried to make medications that affect it. And because it's so consequential for metabolism, people get seizures, like significant side effects of trying to change glutamate. So all the research funding and focus went to the other monoamine neurotransmitters, where you could modulate them without this risk of glutamate. But also, arguably, it lacked the upside of changing glutamate. Glutamate. Someone, I suppose, in Toronto just there, and Robert McCollum Smith, one of the researchers, described it like glutamate is the volume dial and the other neurotransmitters are the treble bass. And it's like the big one, but you just can't do anything with it without people having severe side effects. Whereas ketosis is creating, like you described, a metabolic shift in the brain that leads to a change in neurotransmission that doesn't have these types of side effects associated with some of the early ways they tried to change glutamate. So I think ketosis as a metabolic way of improving glutamate metabolism in the brain is a promising area for investigation. And I have a paper on this in Nature Journal Molecular Psychiatry kind of talking about these dynamics of glutamate and.

How it's such a shame because you know, you're talking about such simple interventions that cost very little, that are diet related or pennies of potential supplements a day.

Yes.

And you know, there's funding that comes from some interest in philanthropists.

Yes.

Very little from any governments and none from the pharmaceutical industry because it's not in their best interest, number one, to study this. And two, it's messes up with their business model, which is selling people lifelong drugs for psychiatric care. In fact, I think it's the third leading class of drugs that are prescribed out there after statins and GI drugs or maybe a second. It goes back and forth between GI drugs and psychiatric drugs. And many of these drugs are, are tremendous side effects, they're marginally effective and they don't really cause cure, they don't really cure the problem. They just maybe mitigate symptoms and they often don't work that well or they may sometimes make things worse in other ways. So for you, you know, in a lot of people you're studying, you know, recovery is possible now. I mean, you know, we never really thought it was possible to cure these problems but, and maybe it's not perfect for everybody because there's many complicating factors. But many people have such a stigma around mental illness and such, such a, they're so pathologized in how we talk about mental health. I mean, if you have, you know, rheumatoid arthritis, no one like stigmatizes you. You know, it's always too bad that they have arthritis. But like when you have mental illness, it's like, you know, those homeless people on the street are, you know, these, and they're, it's like, it's such a, it's such a stigma. And how do we need to kind of evolve this whole idea about, about mental illness?

I actually wanted to ask you about the, the Foucault text. You mentioned that there's different conceptualizations. I'm interested in that. What were the ones that you noticed.

In the book that he talked about?

Yeah, I'm interested.

I mean, you know, it's a fascinating book. I mean I read it 40 years ago, so I'm not sure I remember the whole thing, but it really struck me that at each time in history there were different ideas about mental health. And, and, and, and it could be that you were, you know, basically possessed by demons or it could be that you were, you were, you know, kind of, you know, visited by Angels and God. You know, I mean, think of Joan of Arc and she probably was crazy, right? But what was going on there? Yeah, you know, and there's many people throughout history like that and, and they, they often had outsized effects and then, you know, the, the Freudian view and then now is a different view. But I think now we're coming to a more sophisticated scientific view or be really ask the questions in a way that we never were able to ask before. So yes, I think, I think this is incredibly hopeful moment in psychiatry. I think it's not happening fast enough. I think most people haven't heard of all this stuff before, which is why you're coming on the podcast. And I think. You know what, I would, I'd love to hear about you now. Presented at Mayo Clinic. You've published in major, major journals like Nature. This is starting to get some play out there in the scientific world. Tell us about the Metas Molloc psychiatry hub that you helped develop in the UK and what are you hoping to see in terms of the work you're doing? And I know you're developing a large randomized controlled trial which is sort of the gold standard of evidence. What are you looking to show with that and tell us more about that?

So I mean, the hub for metabolic psychiatry and Edinburgh is a really remarkable thing because as you know, metabolism has not been a major focus in psychiatry.

For a long time, despite all the metabolic problems patients have had going back to the most earliest observations of psychiatrists. And so we put in a bid to the Medical Research Council in the uk, which is.

Essentially the largest government funded research funding scheme. And it's a really competitive scheme. Each university gets one application, so you have to be the best application in the university. And then every university in the UK puts in an application and they choose the best ones from those applications.

It's pretty competitive.

Yeah. There couldn't be a more competitive scheme essentially because it's so high quality.

But I think one of the things that we were able to show, and this is a major patient priority, millions of patients having these metabolic problems alongside their psychiatric diagnosis. We know this, the data has been there for, for many decades now. And this is a prime concern of patients, a huge contributor to suicidality and poor physical health outcomes. And so it's really clear that regardless of what anyone thinks about what causes psychiatric illness, one thing we do all agree on is that we need to fix physical health and people living with mental health conditions. It's a major priority. And the data shows that psychiatrists Know this, clinicians know this, patients know this. We all agree we need to work on this and so there's a clear area that we can make progress. And so we were funded.

About 4 million and the bouzouki has also provided co funding for it to really start a large government funded program to investigate metabolic health and mental illness, which is fantastic. And we have work streams on genetic research, population health data, clinical trials, patient experience, and really we're trying to bring the patients.

You got the award, you won the prize.

Yes, yes. Which is fantastic. Yeah.

Congratulations.

Thank you, thank you. But I appreciate that people like your yourself have been sounding the bell on this for decades leading to this. So, you know, it's really like the.

Dam is now shouting in the wilderness and somebody's finally recognizing it. It's quite helpful.

Yeah. But I mean, that's what's led to this momentum is people such as yourselves, like I say, Chris Palmer, Georgie Ead really ringing the bell for a long time before this came about and this has led to now the dam breaking and there's really sort of major government funding coming behind this and I think it's the right time for. For it. And I wanted to thank you for, you know, raising this and speaking about it for so long before there was support for it. So it's really a remarkable thing to see it now reaching this level. Yeah.

Thank you. Yeah. Well, they first you say some new idea, they think you're crazy.

Yes.

And then they say, well, maybe there's something to it. And then they're like, oh, we thought this all along.

Yes, exactly.

It becomes something like that. So for people listening out there who are struggling with mental health issues and who've tried a lot of things and feel like it's a lost cause, you know, what would you want them to know?

It's really hard living with these conditions. I was very fortunate because I had a, in my family, my mother, like I said, a brain aneurysm and was really had, you know, severe symptoms for a long time. And my father essentially looked after, whilst working, whilst looking after all of us. And at the same time I was living with bipolar disorder. And I was very fortunate to have. Have a family that were supportive of me, particularly my father, who was looking after not only my mother, but also myself. And I was very, very fortunate to have that. And I really empathize with people that don't have that kind of support in their life. And so I would say that the first thing is to find someone that can really look out for you and that you can trust. And hopefully that's a family member. But maybe if not, it can be a psychiatrist, a doctor. And if you don't find the right one, you just keep trying until you find, find you really need one person in your life that's looking out for you, that's going to not give up. And for me, that was my family. My wife has been very supportive, my father. But I'd say that's one of the keys to surviving this, is to really have someone that you can trust. Because there's times when your brain isn't working well enough to know what to do yourself. And you need someone that you can trust to speak to. And the second thing is just to really educate yourself about the condition. Because we're advancing science very quickly now in understanding these conditions. And our understanding is evolving each year, and these metabolic aspects of the condition are becoming much more in focus as we go on. And so to really access resources, try to understand what the condition is beyond these. You're saying about these maps that don't fit the territory. There's so many maps that we've been through, and there's new maps evolving that are better fitting the landscape. And I think metabolic psychiatry country, there's resources like metabolic mind or YouTube channels or places where you can find information about mental health and metabolic health that could be useful.

That's amazing. So thank you. You know, your work is just so tremendous and I can't wait to see what comes out in your, in your clinical trials. We're going to be keeping a close eye on what you're doing at the University of Edinburgh. From my perspective, there's so much hope out there for people who are struggling with mental health issues because we, we now have a new way of thinking about it based on root causes, based on the body as a system and systems basically medicine for psychiatric illness. It's, you know, the application that is functional medicine. But a lot of people who are outside of functional medicine are coming to the same conclusions just by seeing what the data shows and following the breadcrumbs and the data, which is what I did. And we're using, you know, multimodal diagnostic tools, you know, genetics.

Yes.

Blood biomarkers, metabolomics, brain imaging. To really, really move beyond this whole just listing of symptoms and one size fits all. You have bipolar disease, you get this cocktail drug, you're schizophrenic, you get this cocktail of drugs, you're depressed, you get this cocktail of drugs. That era is over for anybody still trying to figure this out, try to find a good functional medicine doctor. You can go to ifm.org, you can come see us at the Ultra Wellness Center. We've been dealing with this for a long time with great success. And we have to kind of move away from this idea of just this maintenance of, of drug therapy and compliance with drug therapy instead of kind of moving to a more recovery model where you can recover, you know, like, can you recover from autism? Can you recover from Alzheimer's? Can you recover from schizophrenia? Can you recover from bipolar disease? The answer, if you would ask most physicians would be no. But we're now learning the answer is hell yes, you can. And there's examples of this all around, and I've seen it personally, I've had patients with this who've recovered over and over again using this model. So to me, it's an incredibly hopeful time and what we really needed. And you know, instead of a bunch of guys who aren't, you know, scientists like me, I'm a doctor, you know, just saying a bunch of stuff that sounds crazy, we now have folks like you who are actually doing the hard academic work at top universities around the world like Harvard and Stanford and Mayo Clinic and University of Edinburgh, who actually mapping out what a future of psychiatric treatment might look like. That, that destigmatizes illness, that gives people hope, that provides a road map for trying things and people can try things. I mean, you know, I think that's really why I, I write the books that I've written. The ultramind solution is, is a little dated, but it's still ahead of its time. And if you follow things in there, it often will work. You know, I have so many patients, people going to just say, Dr. Hyman, I read your Ultra Mind solution. I cure my bipolar. I'm like, you did? Like, yeah. Good. Okay.

I mean, like reading that chapter back, it's funny how much it fits that now the research trajectories that are coming into mainstream, it's really remarkable. Mitochondrial function, energy metabolism, those kind of.

Biomarkers, gut microbiome, all of it.

Yeah, yeah. And now we have things we can potentially do. You know, we need to do large RCTs. We're in the early pilot stages of research. So, you know, I'm not going out saying every woman with psychiatric conditions should just do a ketogenic diet. Diet. We need to really research this in detail and do the rcts and really understand this before. But, but at least there's, there's things that are possible at the moment.

You know, I mean, as a therapeutic trial for six to eight weeks, it takes a little while to become fat adapted, but you know, six to eight weeks, 12 weeks, along with a multivitamin, fish oil, vitamin D. Yes. The magnesium, the methylating nutrients, like B12, B6, folate, pretty little downside to that for most people. And there's a lot of upside. And, and so whatever you're suffering from, like you should, if you can't find someone to tell you what to do, learn about it yourself. And now that, you know, we have access to, you know, I mean, think about it. You know, the average person today has access to more knowledge at their fingertips than ever before in human history. You know, it's some person in Bangladesh has more access to world's knowledge than the President of the United states had in 1960s or 70s.

Yes. Yeah. And I think that there's abundant opportunities to participate now in this, in investigating this. You can sign up for clinical trials as a participant and you'll have full support of a psychiatrist, dietitian in exploring this as a treatment. So this trial's launched all over the world now because of Bouzouki. There's other public funders coming into this now. So there's many opportunities to do this, this in a way that's safe, working with psychiatrist, dietitian and, and it would give you an opportunity to contribute to the scientific understanding at the same time. So I really recommend people as patients try and get involved and try and let's move this forward, let's understand how it works. What are the biomarkers? Yeah, and let's make it.

Yeah, amazing. So we're going to put links to everything called medicsbolicpsychiatryhub.com which is your hub in the UK. Metabolic minds from the Bisky Group is great, great.

There's a lot of papers we talked about. We'll link to those in, in the show notes. Ian, thank you so much for the work you do for being on the podcast and giving hope to millions and millions of people around the world who are struggling. A billion people.

Thank you so much.

It's a billion person problem, right?

Yeah. Thank you so much for helping me on my personal journey with your books and, and for setting the alarm on this for a long time. I appreciate it. Thank you.

Well, thanks so much, Ian. It's been great to have you on the podcast. If you love that last video, you're gonna love the next one. Check it out.