https://youtubetranscript.com/?v=bg-gQ-TnHRw
I was changing people’s diets to help them lose weight and noticing dramatic improvement in psychotic symptoms and mood symptoms and other symptoms. So, okay, so you came at this, you started to understand this because you started to examine diet and you were examining diet, you were examining diet, why exactly? What was, just to help people lose weight? This will take me on a tangent from the question that I’m going to come back to. You ask me a question and I’m going to come back to it. But this tangent is that I had this patient with schizoaffective disorder. He had been my patient for eight years. Schizoaffective disorder is a cross between schizophrenia and bipolar disorder. This man was tormented and disabled by his illness. He had chronic hallucinations, delusions. He was paranoid. He was convinced that everybody in the world was out to get him. People were laughing at him, spying on him, trying to hurt him. He had tried 17 different medications. None of them helped his symptoms. He had gained a massive amount of weight and asked for my help to lose weight. And I put him on a ketogenic diet to try to help him lose weight. And within two weeks, not only was he starting to lose weight, but I began to notice this powerful antidepressant effect in him. And the shocking thing that led me ultimately on this path was that about two months in, so it doesn’t happen overnight, but about two months in, he starts spontaneously reporting that his hallucinations and delusions are starting to go away. That man went on to lose over 160 pounds, has kept it off to this day seven years later. He was able to do things he hadn’t been able to do since the time of his diagnosis. He was able to go out in public and not be paranoid. He was able to complete a certificate program. He was able to perform improv in front of a live audience. Wow. He teaches karate. Now he was able to do things that were all but impossible for him and somebody with his diagnosis. And that, initially, I was just in disbelief. I couldn’t believe what I was seeing and I’m thinking that this can’t be happening. Schizoaffective disorder doesn’t get better and it certainly doesn’t get better from a change in diet. What on earth is happening? So I initially set out on a journey to understand what on earth is the ketogenic diet doing. And that was quickly led to its use in neurology. So although a lot of people know the ketogenic diet as a fad diet or a weight loss diet, it’s actually a 100-year-old evidence-based treatment for epilepsy. And it can stop seizures even when medications fail to stop seizures. And the reason that’s so important to me as a psychiatrist is because we use epilepsy treatments in psychiatry every day in tens of millions of people. We use pills that were originally designed to stop seizures and we use them for a wide range of mental disorders, including depression, anxiety, alcoholism, dementia and schizophrenia, bipolar disorder and others. And so initially that was a really important connection because I thought, well, maybe that’s why this diet is changing his brain symptoms. Whatever it’s doing to stop seizures, maybe those same processes are also reducing his psychotic symptoms. Like reducing excess neural activity, for example. Because you could imagine that that delusional state is a… I’m not saying this is the case, but you can imagine that it is the case, that it is a consequence at least in part of excess neural activity. Now if you have too much neural activity, you’re going to get the electrical storm that characterizes epilepsy. But you could imagine that a man could be in a psychophysiological, neurophysiological condition where the spread of ideas around the core idea is too rapid and too wide. And a delusion certainly looks like that to some degree, especially a paranoid delusion. You even see that to some degree in depression because in depression, one sad idea will trigger an avalanche of sad ideas. So just a thought with regard to the potential overlap with epilepsy. Okay, so you started looking at the dramatic, as you pointed out, dramatic effects of ketogenic diets on epilepsy treatment and started to think if that, given that that dramatic effect on brain states exists, which is clearly documented, right? And no one disputes it, that there’s no reason to assume that there couldn’t be more subtle but still important effects of dietary transformation. And then you became partly convinced of that as well because of the, I mean, the story you tell about one client, and that’s a ridiculously dramatic story because schizoaffective, personality disorders are notoriously difficult to treat. Schizoaffective disorder is a complete bloody catastrophe because it has all of the aspects of personality disorder that’ll produce social alienation, plus all the intense suffering that characterizes the whole hallucinatory nightmare of delusion. So it’s a very, very serious personality disorder, neuropsychiatric condition. And then you saw this dramatic transformation in this one individual, not only on the weight side, which is dramatic enough and unlikely enough, given that most people never lose their weight, right? They’ll lose it for a time, but they gain it back and more. And also the cessation of the symptoms. And also, and this makes it even more complex, because it took two months, this is not an easy thing to discover, right? I mean, the person has to be pretty damn committed to the dietary transformation and also unlikely to cheat in the interim. So okay, so you encountered those. Let’s return to the metabolic story. And so initially, well, and I want to back up just a little bit and just forgive me, but I want to just correct something that you said. So because I’m talking about schizoaffective disorder, which is really the full bread cross between schizophrenia and bipolar disorder. Oh, so this is more than a personality disorder? As opposed to the personality disorder, which is schizotypal disorder. So he had… Oh, I see. So it was even more serious. It was even more serious. He basically had full-fledged schizophrenia. Full-fledged psychosis. Full-fledged psychosis. I see. Oh, okay. And so as I went on, you know, initially, I’m starting to use it with other patients and I’m seeing equally transformative and sometimes even more transformative results. So I know I’m on to something, but I also recognize nobody’s going to believe this. Nobody in the medical field is going to believe that a diet could change something as devastating as schizophrenia. So I need to come up with at least a potential mechanism of action. I need to understand enough science to be able to make the case, to be able to report this in the medical literature. And so the great news is that I had two bodies of literature to call on. So there’s an entire body of literature in the neurology field on how on earth does the ketogenic diet stop seizures? And there are all of these known mechanisms of action, including changes in neurotransmitters, changes in the gut microbiome, decreasing inflammation, all of these things. But one thing stuck out at me. It improves mitochondrial function, which basically means it improves brain metabolism. The other body of literature that I had to look at, though, was the schizophrenia literature and the bipolar disorder literature to see, well, what do we know about the neurology, the neuroscience of those disorders? And is there any overlap? The widely held view is that schizophrenia is just too much dopamine. That’s what schizophrenia is, too much dopamine. But that didn’t sit with this kind of observation that the ketogenic diet is dramatically reducing symptoms. The dopamine thing didn’t fit in. And so I had to look elsewhere, and I was led to this entire body of literature, two decades long now, documenting that mitochondrial problems may in fact be the central root cause of schizophrenia and bipolar disorder. Okay, let me ask you a question there. So, well, the dopamine hypothesis has been around for a very long time, and it is the case, and it’s been a while since I reviewed this, so if there’s anything that I’m saying that’s no longer, that’s out of date, let me know. Part of the evidence for that was that at least with some forms of schizophrenia, you could exacerbate the symptoms with amphetamines and that you could also produce amphetamine-related psychosis. That’s part of the body of evidence. The other part of the body of evidence is that the antipsychotics, the major antipsychotics, do seem to work like anti-cocaine or anti-amphetamine, and they do quell the more florid symptoms of schizophrenia, especially in its acute manifestations, rather than the sort of burnout schizophrenia that’s characteristic maybe of the much longer term illness. And so given the prevalence of that hypothesis and the support for its validity, did you see any overlap between the metabolic hypothesis and the dopamine hypothesis? Is the dopaminergic malfunction in your estimation a secondary consequence of a deeper mitochondria malfunction or do you think that the dopamine hypothesis is more akin to observation of a symptom pattern rather than the core cause?