Remastered Episode: Dr Zoltan Sarnyai ON Ketogenic Therapy for Schizophrenia and Bipolar Disorder

In this episode of our podcast, we dive into the intriguing connection between the ketogenic diet and its effects on mental health disorders, with a special focus on schizophrenia. Our guest, Dr. Zoltan Sarnyai, a seasoned neuroscientist and professor at James Cook University, shares his extensive research on the neurobiological mechanisms underlying psychiatric disorders such as drug addiction, depression, and schizophrenia. 

Dr. Sarnyai discusses his initial motivation towards exploring mental illness, propelled by a personal experience during his medical school years. The episode also covers his transition from psychopharmacology towards the potential of dietary interventions, particularly the ketogenic diet, as a therapeutic approach to treating severe mental conditions. Highlighting a range of case studies and his own research findings, Dr. Sarnyai elaborates on how ketogenic therapy might address the core issues of mental disorders by targeting systemic and brain glucose energy metabolism dysfunctions. 

00:00 Welcome to the Show: Introducing Dr. Zoltan Sarnieh

00:56 The Fascinating Journey into Ketogenic Diet and Mental Health

06:57 A Deep Dive into the Science of Ketogenic Therapy

13:22 Exploring the Impact of Ketogenic Diet on Schizophrenia

36:17 The Future of Ketogenic Therapy: Challenges and Opportunities

47:15 Closing Thoughts and the Path Forward

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Transcript

0:49

I'm so excited for this. We have a very special guest on a podcast today. Dr. Zoltan Sarnieh is a medically trained neuroscientist, and he is a professor and head of the Laboratory of Psychiatric Neuroscience in the Institute of Tropical Health and Medicine, James Cook University in Australia. He also has an active research program in the neurobiological mechanisms of stress and psychiatric disorders, including drug addiction, and depression. Schizophrenia and depression. And one of the leading voices in the advancement of therapies for severe mental disorders. It's just an honor. Dr. Zoltan Sarnieh, welcome to the show. I'm happy to be here. Thank you very much, Lawrence. Thank you so much. You know, Dr. Zoltan, you know, you live across the world, first of all, in Australia, and you stayed up late for us today. And so appreciative of that. And so, and I'm very excited to be. Here with you today, I had a growing fascination with the ketogenic diet and it's meant, and it's effect on mental health, you know, and its benefits, and I stumbled upon your work through the Metabolic Mind Foundation, run by the Balzucchi family. And you are doing such a such great work for the advancement of treatment in ways that are saving people's lives and renewing them in a major way. And so, which is really groundbreaking, especially in treating schizophrenia. And so welcome. And I'm glad to have you. Thank you. So for our listeners who are not familiar with your work, Dr. Zoltan, can you briefly tell us a little bit about your background and how you got into this line of work? How far back would you like me to start? Just maybe how you got into, you know, ketogenic diet and its benefits in treating mental health. Yeah, so I've long been interested in mental illness, even back to medical school. Fascinated and scared at the same time. I have, I think one very formative experience. I was last year medical school and we had our clinical rotations among different departments. So I was at the psychiatry department. At my university in the hospital, and one day I went home and my brother, who just finished high school at the time, asked me about something strange happening with one of his friends. So he described the situation to me, that this young man locked himself in a room. Up in his room, he's not coming out, he closed the curtains, he's not communicating with his mom at all, he's not taking any food, and he's just behaving very strangely. So he asked me what, what I think, and I said, you know, it doesn't look very good, to be honest. And, you know, it remains to be seen, but it doesn't look good. Next morning, literally next morning, I was in the hospital, and this young man, the very same young man, was brought in. handcuffed by the police as he attacked his mother thinking that his mother wants to kill him. So he was immediately institutionalized. I followed him for a few more weeks while I was there and then I graduated and just maybe a year after I bumped into His psychiatrist then asked him about this young man, and he said he unfortunately died, committed suicide, and it really touched me deeply. We were talking about an 18 year old young man, whole life ahead of him, and just like that, he was gone. So I became really interested in trying to understand how this devastating mental illness comes about and what we can do about that. Over the years, I became involved in many aspects of what you would call psychopharmacology, how we can treat mental illness drugs. And this is what I teach at the university. So I had nothing conceptually against drug treatment in severe mental illness at all, but I had to realize that such treatment has limited efficacy in certain people and have very significant and quite devastating side effects in all of the people taking that. So that actually prompted me to really try to think hard what can be done in this situation. When we try to understand the mechanisms of severe mental illness, our understanding is still just at the beginning. Think about the fact that the first clinically used antipsychotic was introduced into treatment in the 1950s, 1960s. At the time, we had absolutely no idea what's going on in our brain, in terms of neurochemical changes, in terms of functional activity of different brain regions. We knew absolutely nothing, especially compared to what we now know. So those drugs originally were discovered by complete serendipity. They were never ever designed specifically to treat these conditions. They just found to be useful and helpful from a medical point of view and probably from the patient's point of view a little bit as well. So these rocks were and still are seriously lacking in their ability to really make life livable and worth living for a majority of individuals, unfortunately. So if you look at the different hypotheses explaining The causes behind and the mechanisms behind severe mental illness, the leading hypothesis for a very long time has been the dopamine hypothesis that schizophrenia is brought about by too much dopamine, too hyperactive dopamine activity in the brain, and the drugs that are used in their treatment are blocking those proteins that bind dopamine and provide relief to the patients. And I always felt this is, uh, not the full picture. It cannot be the full picture. If we block the dopamine system in the brain, yes, we probably block psychotic delusional thoughts. But we block pretty much everything else as well. You can imagine that's the sort of the major psychomotor pathway coming out of the brain. If we block it, yes, we can make some symptoms disappear, but nothing else. So, it must be something a lot more fundamental then. And that gets me to, to your question, really. That was just a rather long introduction to, to, to my real answer to your question. Again, a chance conversation with a friend, former university classmate, who was at the time a researcher at UCLA, working on cancer from a metabolic direction. And we had a very interesting conversation about the importance of metabolism of glucose. Thank you. And how abnormal glucose metabolism contribute to whether we can therapeutically target cancer like that. And it all made sense to me. I remember back in medical school, we were taught that one of the earliest symptoms of cancer is actually unexplained weight loss. So all those cells are using glucose to make DNA and RNA for the extremely heavily dividing cells, building up the cancer cells, rather than feeding the person. And that was a very attractive idea to me, if I think about the brain. So energy metabolism, something absolutely fundamental, required for, All the functioning in the brain, but especially maintaining the most fundamental process, the formation of action potential, the electrical activity of the brain. Without proper provision of biological energy, our brain would collapse immediately. Mm-Hmm. And you can imagine with more subtle deficiencies, the brain doesn't collapse. The person is still functioning, brain is still functioning, but it is mal functioning. It's not functioning as it should be. So I became very interested in that idea, conducted a few experiments that was back in my time in, in, in Cambridge, England with a collaborator there. And we found something very interesting. We use the pharmacological animal model of schizophrenia and if you are interested, we can talk about, you know, modeling complex psychiatric disorders in. In, in rodents, which is an interesting topic on its own, but in this model, which actually capitulates lots of the behavioral abnormalities we see in schizophrenia, we also find insulin resistant, elevated glucose level, which are features of acute first episode drug treated individuals with, with schizophrenia and bipolar disease. So that further underlines to me that there are a systemic metabolic abnormality in the whole body, but in the brain as well. In the same experiment, we found abnormal expression of genes encoding for enzymes that are important in breaking down glucose in the brain. So that really put me on the trajectory of looking into potential therapeutic avenues to circumvent an abnormal glucose and energy metabolism. And around the time, many other researchers became interested in this field and Um, and exciting data were coming out. So I thought this is something very, you know, seriously worthwhile. And then again, completely accidentally, I bumped into the idea of ketogenic diet. I was not at all in the diet field, not at all. I came from a sort of a psychopharmacology background altogether. So I think about epilepsy and the fact that ketogenic diet is effectively. Controlling epilepsy in children, and it's been used for over 100 years now, and then if you look at what ketogenic diet does and what ketones do in the brain, they circumvent this glucose metabolism altogether. And they feed other biological processes to make the biological substrate of energy, ATP, adenosine, triphosphate, without relying the glucose metabolism. So I thought, wow, that's really interesting. We set up an experiment, an experiment in a mouse model, to test the idea. Well, if you have a hypothesis. Which you would like to test, you should never try on, try that on human beings, because obviously it's not ethical, and it's not practical either, and we all have ideas, and not all ideas actually work out all the time. So you have to do pre clinical studies to provide a proof of concept that idea should work. Uh, should be valid and further followed up in, in humans. And we selected the model which, uh, actually based on strong human findings. So it's been known for a long time that certain drugs of abuse, such as AngelBus, which is fancyclidine, and ketamine in high doses can produce psychotic episodes. in indistinguishable from schizophrenia. And we know how these drugs act. They block a certain receptor in the brain called the glutamate receptor, and that contributes in the behavioral abnormalities. If we replicate this situation in mice, we can recapitulate the main characteristics of behavioral and cognitive features of human schizophrenia, which you can summarize into positive, negative, and cognitive symptoms. We, of course, don't know whether mice hallucinate and have delusions. We don't know, and they most likely, they don't, because these are the products of the human brain, the non human species. probably do not exhibit anything or experience anything like that. But there are parallels in the mouse behavior that might be sort of modeling and similar to what you can find in humans. We also identify that these animals have cognitive abnormalities in their working memory, just like people with schizophrenia. We also, we also, demonstrated that these mice actually have social abnormalities. They became asocial, they do not interact socially with other mice. Again, an important feature of psychotic disorders. So in this model, we administered ketogenic diet, mouse equivalent of ketogenic diet, of course, to To our surprise, to be honest with you, we were able to normalize the entire behavioral spectrum. So these animals recovered all together after three weeks on ketogenic diet. Of course, we demonstrated that they were in ketosis. They had elevated beta hydroxybutyrate, which is the laboratory hallmark of being inky. They had very low circulating glucose, as one would expect from a diet that is very low in glucose. That was the first demonstration of the efficacy of ketogenic diet in animal models, schizophrenia. We published that in 19, in 2015, and followed that up with a number of other papers further investigating the same question in different models. And all of this are, is because there's a dire need to look for other alternatives because of the drugs to treat schizophrenia or severe mental disorders are not doing the job. Basically, It's only attaching itself into one receptors, which can also have, you know, a wide ranging side effects. I appreciate that story and I appreciate and we're going to break it down in a second here. It's just an amazing story. When you. Begun with that story with the friend of your, was that the friend of your brother? He said, it's just a great story. And that, you know, spark your interest into looking into more of how you can, how does this work? Right. And it's just a great story. And I want to, on your recent case study in, was that in 2015? You said, you talked about the fundamental mechanism of, you know, is that when the ketogenic diet came to your radar in 2015? Yes, yes, yes, of course. When you try to dig deeper in the literature, you quickly figure out that there is nothing new under the sun. People obviously thought about that. Long before, literally, there was one publication from 1965, small cohort of 10 women with schizophrenia put on a ketogenic diet and showed very significant improvement. It wasn't a properly designed and run randomized controlled clinical trial at all. It was just switching them to ketogenic diet, observing their behavioral changes. The diet wasn't properly described, at least not at today's publication standards. But that was an indication. And then fast forward to, I think it must have been 2008 when another case study was published. That was one single individual, a lady who was 70 years old at the time with chronic schizophrenia, under care, multiple antipsychotic drugs. very significant weight gain. Actually, she was put on a ketogenic diet to control the weight gain, and to the surprise of the doctors who managed, her psychosis completely disappeared. She then, on her own, started to taper off and completely stopped taking anti psychotic drugs. And we are talking about someone who had been suffering from schizophrenia for the best part of her life. And interestingly enough, the very same patient was followed up further and described 10 years later. And that's a paper Christopher Palmer from Harvard contributed. That lady, at the time, was 80 years old, living on her own, completely independently, still on ketogenic diet, and functioning perfectly well for her age. Wow. Wow. And that's unheard of in that time. Yes, pretty much. That was a surprisingly strong response, which you would almost never see, probably never see after traditional foreign political approaches. I was reading the case study you sent me, it was, it's just a fascinating read because Um, I had a, an experience with psychosis firsthand myself when I was about six, seven years ago and ketogenic diet has really renewed my life. And so I really want to get into that, but first let's, let's explain to our listeners here, how was the use of the ketogenic diet? I know we identified that it was being used in. Epilepsy a hundred years ago, and it's, it hasn't, it's been discovered for a hundred years, but, um, to manage severe mental illness, how, what, how do we view ketogenic diet now for schizophrenia? How is it viewed now? And what does the literature say today? So I think first of all, we have to point out that ketogenic diet is not routinely clinically used. to manage or treat schizophrenia and other psychotic disorders. It is still very much in the experimental phase. We would like to understand what it does, really, and how it's doing it. So what is the mechanism of action? In order to have that kind of understanding, case studies are encouraging and absolutely need to be done and report. But they, from a scientific point of view, they kind of fall short of the strong scientific proof that is required for a significant new claim, if you see what I mean. In order to have such data, randomized controlled clinical trials need to be conducted. So we have individuals with the disorder of interest, in this case schizophrenia and bipolar disease and schizoaffective disorder, they are randomly assigned to either ketogenic diet or some other dietary intervention. And I think it is important that it is a dietary intervention. We have to keep in mind, in psychiatry, patients do respond to care. They respond and improve if they are being looked after, if they are being talked to, if they are being asked. So we have to control for that. We have to control for that. For example, in antidepressant research, antidepressant clinical trials, there is a 50 percent placebo response. Because people suffering from depression get better by being taken seriously, being talked to, being regularly followed up, having the ability to talk about their condition. That improves their condition. But that's not the effect of the drug, of course. Or it's not the effect of the treatment intervention. And in a proper clinical trial, you need to sort that out. in order to be able to prove that it is really your dietary intervention is the one that is doing the trick. That's why the patient isn't eating, not because They are in a clinical trial, and they are regularly talked to, so it's very important. We'll talk about the advancement of the ketogenic therapies in a second here, but I want to, for our listeners, I want them to understand what are the conventional common treatments for individuals. You know, I know, You talked about drugs that are used to reduce symptoms and we, earlier you talked about the positive, negative and cognitive symptoms where the three categories can only possibly change, you know, the visual hallucination, disordered thoughts, but where the fallout is, you know, it's resistant in, you know, the negative symptoms, which is, it doesn't help with Emotional response, lack of motivation, and then the cognitive attention disorder. That's absolutely correct. And then, not to mention, there's a wide range of side effects that comes with that. That, you know, we can get into later on. But doctor, what has been the challenge to create a drug that reduces all the symptoms, that mitigates all the side effects? So if you consider the more recently developed and introduced antipsychotics, called the second generation or atypical antipsychotic drugs, that we don't close up the others, they tend to produce Rapid weight gain. And on that background, insulin resistance and type 2 diabetes and resulting cardiovascular disorders emerge. So people with schizophrenia live about 17 to 20 years shorter than people who are not having schizophrenia. And that's not because they commit suicide. Some of them, unfortunately, do. But because of the early cardiovascular diet that is contributed by several different things, of course, the fact that they are not able to go out because they avoid social situations, they have their fears, their delusions and hallucinations, they don't go out, they tend not to exercise. They tend not to, to eat healthy. Some of the antipsychotic drugs actually preferentially increase carbohydrate and the intake of highly palatable Western diet type of food, which are heavily contributory, heavily, heavy contributors of insulin resistance and resulting metabolic syndrome. But at the same time, the drugs themselves, Contribute to that in a significant manner because as you mentioned, they bind to certain neurotransmitter receptors in the brain that contribute in the behavioral improvement on one hand, but at the same time, they interact with metabolic processes, they interact with eating behavior, and these effects cannot be separated with a pharmacological agent. Yeah, yeah. Which makes. You know, researchers look into another direction for now, in the study, it was, you know, you study, you sent me, it was observed that the ketogenic diet therapy acts through multiple mechanisms. And you talked about a little bit about that earlier. So the emerging understanding is that schizophrenia is a disease of abnormal systemic and brain glucose and energy metabolism, which is a level of insulin resistance to the brain. Is that right? Right. I think that this is, this is a good summary of that hypothesis. Probably, we cannot claim that every single individual having the diagnosis of schizophrenia and bipolar have a condition based on this mechanism, but it is not unlikely that some percentage of them are. underlie by an abnormal brain and systemic energy metabolism. And this is what ketogenic diet able to circumvent and beneficially influence and therefore contribute to the improvement of the symptoms. At the core of the condition, rather than just the main output psychomotor pathway being blocked and therefore hallucinations, delusions are eliminated. So the hope with this metabolic therapeutic approach is that we are aiming for the core underlying mechanism, which involves abnormal glucose breakdown, And also the abnormal functioning, the impairment of mitochondria. So the mitochondria are the little tiny organelles within every cell in the body. that are capable of producing the biological energy substrate, the ATP molecule. So the energy production, how does the ketogenic diet targets and essentially heals the mitochondria? What's the mechanism there? And then they fuse with other cells. and took over the job of producing ATP and using oxygen for that. And that was around the time of the evolution of our Earth. When the oxygen concentration suddenly increased in the atmosphere, and if we have too much oxygen, and we can't deal with that, and if tiny single cell organisms do not have the machinery to use that oxygen, they will die. Because three oxygen radicals will be produced, and those are detrimental to cells. And suddenly, these tiny little creatures, these mitochondria, were able to utilize the extra amount of oxygen. And they utilized it in a way that they produced something that is tremendously useful. And that became tremendously useful for their host cells. mitochondria became integrated into our cells. And the other really interesting aspects of these spinary things that they have their own genome, they have their own DNA, because they are used to be freestanding cells on their own run. So they produce proteins, they produce really important proteins that are involved in making ATP in the mitochondria. And then there is actually a fair bit of evidence from human studies that this ATP making machinery is also faulty in the mitochondria of people with schizophrenia and bipolar disease. Dr. Zoltan, thank you so much for explaining that to us. So essentially mitochondrial impairments, like you talked about, has always been recognized in schizophrenia. Is that right? It's long been recognized. That's right. Yeah. Yeah. There is, there is a lot of evidence coming from different cell types, even from peripheral cell types, blood cells, for example, but there is a strong evidence supported by careful and well conducted systematic reviews and meta analyses. Clearly showing mitochondrial abnormalities. There is some preclinical evidence showing that in animal models of schizophrenia, the transplantation of healthy mitochondria normalizes the symptoms. Which is a really strong evidence and support for the contribution of the abnormal mitochondrial, the underlying behavioral abnormalities. And how does the ketogenic diet targets essentially in helos It, could you repeat please? My question was, you know, we talked about how the ketogenic diet is, you know, function in me, different me mechanistically approach. And one of these is. fixing the mitochondria impairment. What is the ketogenic diet? So this is an area that is still very heavily investigated and we still do not have the full understanding. But what happens in the body during ketogenic diet is that because of the lack of glucose, which is the primary source of chemical energy in the human body, including the brain, because of the lack of glucose, uh, the body relies on fat and the metabolism of fat as energy source. And that takes place in the liver, which converts these fatty acids to ketone bodies. And there are three different ketone bodies, acetone, acetoacetate, and beta hydroxybutyrate. Acetone goes out by, through our breath, through the lungs, but acetoacetate and beta hydroxybutyrate They are able to enter into the brain taken up by the different brain cells, neurons, but not only neurons, the other supporting cells, the glial cells, also take up beta Hypocyte butyrate and convert beta Hypocyte butyrate to one of the intermediary molecules of glucose metabolism called glucose. Thank you. Acetyl Coing A and then it feeds into the cycle that produces the substrates for the production of a TP in the end. So that is certainly one metabolism. Beta hydroxybutyrate has several other ways influencing neuro function. Um. It's been recently demonstrated that beta hydroxybutyrate is also an epigenetic modifier. So this is a big word, but what it means, it interferes with the ability of the DNA to open up and start expressing certain genes. So that's a really important and recently discovered butyrate. We do not yet understand how this bit actually contributes in improving mitochondrial function, but that is certainly one possibility. Another mechanism that certainly takes place influences the production of two key neurotransmitters in the brain. One is glutamate, the other one is gaba. So GABA or gaba amary acid is the main inhibitor in neurotransmitter in the brain. Its job is to control the hyperactive, excitatory cell. In response to ketogenic diet and beta hydroxybutyrate administration, brain cells produce more GABA, more of this inhibitory transmicron, and that could be a mechanism that is in place. For example, it is not unlikely that some of the anti epileptic effects of ketogenic diet is mediated by elevating GABA levels. And there is a completely new and uncharted territory here, which I'm almost sure plays a role. We are just at the beginning to really decide here. What is the role of the gut microbiome? So think about this. We are talking about a diet, something we eat. So what we eat, when we eat something, that gets into our gastrointestinal system, into the stomach and into the small intestines, large intestines. And our intestinal system is populated by trillions of bacteria that live in a happy, symbiotic relationship with us. In fact, we have more bacterial cells in our body than human cells. Maybe we are just the carriers of the whole ecosystem of bacteria. So then, then ketogenic diet is administered. These bacteria change, of course, because there are bacteria that thrive on glucose, so those disappear, and there are bacteria that can take advantage of beta iricebutyrate and the fat. Altered profile of the gut microbiome can be a really important mechanism, because the gut microbiome does many different things. During the last ten years, It was discovered that the gut microbiome directly influences the brain through several different ways. These bacteria produce chemicals and these chemicals get into the bloodstream and through the bloodstream, they get into the brain. And as I said, we are really just at the beginning to see very likely that the gut microbiome and their metabolites, Circulating molecules produced by them play a role. Some people even go so far as people call it the second brain and it's thought to communicate like with the brain plays a huge role. Yeah. Yeah. And what we cannot deny Dr. Zoltan is just the stories that we have heard here today, right? You talked about the 10 women in 1965. And in 2008, you talked about the 70 year old woman, right? That had chronic schizophrenia. And now she's reporting to have no hallucinations. And she improved her energy levels and lots more case studies with the same results. Exactly. We cannot deny what's going on. Now, it's more on just what's going on. How do we explain this? How do we now push this through and advance the ketogenic diet therapy for schizophrenia? Now, doctor, my question for you, what needs to happen now? What else needs to happen? Is it? Do we need to control randomized trials before we can? finally say that this is, this should be the standard care. What needs to happen in your mind? In my view, having positive data from properly conducted randomized controlled clinical trials with sufficient number of patients enrolled, that is really important. It is also important to understand. the potential side effects of ketogenic diet. I would rather prefer to use the term ketogenic therapy than ketogenic diet. We should consider the ketogenic therapy just like any other pharmacological drug intervention. Anything that has a beneficial effect on the body will have side effects, by definition. These are biologically powerful molecules that do things in the body. So we need to understand what they are. We need to understand who respond to ketogenic diet and ketogenic therapy and who wouldn't. We need to understand that. We have no reason to believe that everybody uniform will respond to the diet. No drug does that, actually. So that is crucial. It is, it is also important to sort out that it is the whole diet, or is it the whole diet? Or is it the ketones that circulate in our body as a result of being in the dark? We don't know that for sure, really. We don't know. And that's another important question. Because that in fact goes beyond scientific interest. It has profound practical applications. Do we need the dietary approach, or can we somehow alter the metabolic process similar to what ketogenic diet is doing without actually having to be on the diet? Yeah. Because as you know, being on any diet is very difficult. Compliance. Keeping a rigorous dietary regime is hard, being that any kind of diet, but ketogenic diet can be particularly difficult to start. People who experience the benefit of ketogenic diet, they do not find at all difficult to remain on the diet because they do realize that the significant improvement in their condition. There is, there is one other issue here which needs to be discussed, considered, and have some sort of solution. Mentioning an intervention which involves ketogenic diet. High fat containing food does not ring the right kind of bells in the medical establishment. But neither in the general public. As a result of decades of promoting low fat lifestyle. Right. And not considering the potential consequences of the high carbohydrate input. We know now that the metabolic abnormalities are due to the insulin resistance. And insulin resistance develops as a result of the bombardment of the body. with refined carbohydrates over a long period of time. And it is just becoming the focus of attention, probably not completely independently from the emergence of dietary approaches, such as the ketogenic diet and seeing the beneficial effects of such dietary interventions. So essentially, doctor, you're saying it has to go through the standard due process and with the wide ranging benefits of the ketogenic diet. I'm curious, how long would that take? Are we going to see it in our lifetime? Because like we talked about, ketogenic diet for epilepsy has been around for a hundred years and we've seen That is a very interesting point. A profoundly interesting point. And we, in the field of psychiatry, should learn from neurology. We should learn from the case of ketogenic therapy in epilepsy. Because, as we mentioned already, it was first described and published in 1920 or 1921, so more than a hundred years ago. And it was found to be effective. As we said, diet is difficult. And then the drugs came out, the anti epileptic drugs came out. Those took over the field entirely. Until about 20 years ago, Eric Kossoff and his colleagues at Johns Hopkins University revolutionized that field, reintroducing ketogenic diet in the management of childhood epilepsy with great efficacy, and there are large scale meta analyses published by Cochrane Reviews clearly demonstrating efficacy of ketogenic diet in childhood epilepsy. And if you look around the world today, pretty much all self respecting childhood epilepsy clinics have a ketogenic diet program. It is beneficial, but you're right. We absolutely have to look at that case closely and learn in terms of the other side of your question, how long will it take? I don't think that it should take that long, to be honest with you. And the reason for that is that we have much better tools now than our colleagues back in the beginning of the 20th century had. So now we can look into mechanisms relatively quickly. We can set up the proper clinical trials. And there are major efforts. You mentioned the Suzuki Brain Research Foundation. They are absolutely committed. financially and in every manner possible to provide resources to push this field forward. And that is absolutely crucial. That's very important for the field. Not only the, the financial support, but putting investigators together to work as a team, which is actually sometimes unique in science because we tend to be competitive. We tend to want to be the others, want to publish first. But what they are creating is actually quite different. So my group is working on a randomized control trial for ketogenic dieting, bipolar disorder, and schizophrenia. And there are a few other groups. We're working on that as well and we talk to each other, we talk to each other very intensively. We share ideas, we share data, we share clinical trial design, and that is going to move the field forward much faster. I believe that everyone you mentioned, the Bazooki family, yourself, everyone who's, you know, working towards pushing and advancing the ketogenic diet therapy for mental health disorders. Everyone has the same interest and that's to help people, you know, get better, live their lives, right? You guys have empathy. Back to your question, how long will it take? Another important aspect of that is, how long does it take to shift thinking in the profession. And it always takes time for very obvious reasons, but I think the tide is clearly shifting and there is an increasing appreciation of underlying brain and systemic metabolic processes in severe mental illness. First of all, even the fact that the brain is not functioning alone, the brain is very heavily interacting with the rest of the body, psychiatry doesn't stop here. The rest of the body also contributes to what makes us human in terms of brain function. And I think it is more and more widely accepted, at least in the research sphere. of psychiatry. That will trickle down to practitioners as well, probably in, in the not so distant future. And a new field, or subfield if you'd like, is being formed, metabolic psychiatry. New approach, a completely revolutionary approach to understand severe mental illness. considering glucose and other metabolic processes, mitochondria and systemic metabolism being all part of the picture. That's all great to hear Dr. Zoltan. That's amazing for people to hear. Dr. Zoltan, thank you so much for coming on and sharing your story and that we've learned a lot today about how effective the ketogenic diet therapy can be for our mental health. Severe mental disorders like schizophrenia, and I urge everybody to relisten, really, uh, relisten to the episode, take some notes. There's a lot of things here that are new and are very, you know, if you know somebody who's suffering from schizophrenia, right, or bipolar disorder is one as well, you can share this information to them and so that they can have a more informed decision. Going forward. Dr. Zoltan, thank you so much for coming on and sharing your story once again. Did we miss anything that you want to share? I think just one final remark. I'd like to emphasize that people with schizophrenia and bipolar disease and other psychotic conditions, they should consider ketogenic therapy as a medical intervention, as a proper medical intervention. It's a little bit beyond just a lifestyle diet in that case. Of course, ketogenic diet can be a lifestyle diet, and many people are on ketogenic diet as a lifestyle diet. But in the case of severe mental illness, it needs to be considered as a medical intervention. And proper medical support is required. Measuring laboratory values. blood glucose, insulin, blood lipids. There will be contraindications. There will be people who will not be suited for ketogenic therapy because of their underlying systemic conditions. And these are important things to consider because we have to remember our main and most important thing in medicine is to do no harm. And we absolutely would like to avoid that. Absolutely. Absolutely. Thank you so much for that statement, Dr. Zoltan, and where can they find your work, doc? So, my research website can be found at the James Cook University's website. If they Google my name, it will come up. With some recordings as well, and information about the research, what we are doing, the clinical trial, what we are preparing to start in hopefully the very, very near future. Yeah, and I'm happy to share what we learned with anyone who's interested. Thank you so much, Dr. Zoltan for coming on once again, and I really appreciate you for sharing your journey here and sharing what you know and what you've learned and what we can expect in the future. The future is bright for us, for a lot of people. Thank you so much. It's been my absolute pleasure, Lawrence. Thank you very much for the opportunity. Awesome.