Good afternoon, everyone, and welcome to our webinar this afternoon. I'm Dr. Terry Brister, Chief Program Officer at the National Alliance on Mental Illness, or NAMI, and also a member of SMI Advisors Clinical Expert Team. It's my pleasure to have you all on the webinar with us today on the topic of Metabolism, Mental Health, and the Ketogenic Diet. Next slide, please. SMI Advisor also knows the Clinical Support System for Serious Mental Illness is an APA and SAMHSA initiative devoted to helping clinicians implement evidence-based care for those living with serious mental illness. Working with experts from across the SMI clinician community, our interdisciplinary effort has been designed to help you get the answers that you need to help care for your patients. Next slide. And Dr. Palmer, I'm not seeing them advance. Ben, if you're able to hear on the other end, are they advancing on your side? Yep, they're on the right one. Okay, terrific. So today's webinar has been designated for 1 AMA PRA Category 1 Credit for Physicians, 1 Continuing Education Credit for Psychologists, 1 Continuing Education Credit for Social Workers, and credit for participating in today's webinar will be available until October 3rd of this year. Next slide. Slides from today's presentation are available in the handouts area found in the lower portion of your control panel, and if you'll select that link, you'll be able to download the PDF of the deck. Next slide. We want you to feel free to submit your questions throughout today's presentation by typing them into the question area, and this is also found in the lower portion of your control panel. We'll reserve the last 10 to 15 minutes of the presentation for questions and answers. Next slide. And now it's my pleasure to introduce you to the faculty for today's webinar, Dr. Christopher Palmer. Dr. Palmer is the Director of the Department of Postgraduate and Continuing Education at McLean Hospital, and also an Assistant Professor of Psychiatry at Harvard Medical School. In his role at McLean Hospital, he's developed hundreds of educational conferences, workshops, grand rounds, and other professional educational activities. He's held numerous leadership positions in the continuing education field beyond McLean Hospital's program, including serving on leadership, advisory, and strategic planning committees of Harvard's Medical School, Partners Healthcare, the Massachusetts Medical Society, and the Accreditation Council for Continuing Medical Education. Dr. Palmer, thank you so much for leading our presentation today, and I'm looking forward to it. Thank you, Dr. Brister. So before I get started, I've got a few disclosures. One is that I do have a book coming out, Brain Energy, later this year, but otherwise I have no relationships with any commercial entities related to the content of this presentation. I do want to discuss, you know, the ketogenic diet is a very controversial diet, and the research that I will be sharing with you, especially on serious mental illness, is in its infancy. There are risks with ketogenic diet that I will go over, and I really do want people to take them seriously. Ketogenic diet is usually not a standalone treatment, and I will review kind of a comprehensive treatment plan, which might include medication, psychotherapy, and other appropriate mental health treatments. And clearly more research on this topic is needed, but is already underway that I'll share with you. So let me tell you what I'm going to go over. I'm going to, hopefully by the end of this presentation, you will understand what the ketogenic diet is and the different versions of the diet. You'll be able to identify some mechanisms of action of the ketogenic diet, and outline some of the scientific rationale and evidence for using this diet in epilepsy, depression, alcohol use disorder, schizophrenia, and bipolar disorder. But first I want to start with this connection between what we call mental disorders and metabolic disorders. So it turns out that mental disorders and metabolic disorders have a bidirectional relationship with each other. And what do I mean by bidirectional relationship? What I mean is that if you look at a group of people who have mental illness, they are much more likely to develop or already have obesity, diabetes, and cardiovascular disease. But if I do it on the flip side, if I look at a group of people who are obese, or a group of people who are diabetic, or a group of people who have cardiovascular disease, they are much more likely to have mental illness. So this relationship between mental illness and obesity is pretty well established. For major depression, people with depression are 20% more likely to develop obesity. But people with chronic psychotic disorders, such as bipolar disorder and schizophrenia, are much, much more likely. Some meta-analyses estimate about three times more likely to develop obesity. And in fact, obesity changes the course of mental illness in some people. Obesity itself changes brain metabolism and brain circuit connectivity. And we've had longitudinal studies looking at people who eat, for instance, a lot of junk food. And after 10 years, they are more likely to develop obesity, which is not surprising. But they're also much more likely to develop major depression. And in fact, obesity itself worsens the course of bipolar disorder. This graph that you see here separates people with bipolar disorder only by whether they had obesity or not. And the obese patients had more mood episodes than the patients who were not obese. Now mental illness and diabetes also have strong bidirectional relationships. And it turns out that these relationships are longstanding. They've been known for over two centuries. In the 1800s, we knew about this. And I want to stress that's before we developed any psychiatric medications. People diagnosed with schizophrenia are three times more likely to develop diabetes. People with depression are 60% more likely. But it's not just the medications that we prescribe. Most people think this is the medications. And there's no doubt the medications we prescribe cause obesity and cause diabetes. It's on the package insert. But in fact, when people come into the emergency room with their first episode of psychosis before we even give them one pill, they already show signs of insulin resistance. And as I'll get to, this is actually really important. But if we look at it the other way around, people with diabetes are more likely to have mental illness. This is best established for the diagnosis of major depression, primarily because depression is a much more common illness than schizophrenia or bipolar disorder. But people with diabetes are twice as likely to have clinical depression. But when they get it, it lasts four times longer than it does in people without diabetes. And depression itself worsens the course of diabetes. Depression itself makes the blood sugars higher, it causes more insulin resistance, and it causes higher diabetes complications. Same deal with cardiovascular disease. People with serious mental illness are 53% more likely to develop cardiovascular disease than the general population. And this is after controlling for all of the risk factors, obesity, diabetes, smoking, and others. Now, the fact that people with schizophrenia and bipolar disorder are much more likely to be obese, diabetic, and be smokers makes this statistic dramatically worse. Depression itself is also a risk factor for cardiovascular disease. In people who've never had a heart attack, depression itself increases the risk for having a heart attack by 50% to 100%. And if you've already had a heart attack, depression doubles your chances of having another heart attack. And if we look at it on the flip side, people who have just had a heart attack or have congestive heart failure, 20% to 33% of these people have clinical depression. That is five to seven times larger than in the general population. And in fact, the American College of Cardiology now recognizes major depression and bipolar disorder as independent risk factors for having a heart attack. And all of this translates into something that probably is not that surprising to many of you. People with mental disorders die early deaths. We have long known that people with schizophrenia and bipolar disorder and chronic depression die early deaths. Depending on what study you look at, the reduction in lifespan is anywhere from seven to 30 years of life lost. But in fact, a recent large population survey of over 7 million people found that all mental illness, all of them, depression, ADHD, anxiety disorders, personality disorders, all of them are associated with a reduction in lifespan. On average, men are losing 10 years of life. Women are losing seven years of life. What are they dying of? Heart attacks primarily. It's not suicide. Everybody thinks these statistics are skewed because of suicides. There's no doubt that people with mental illness are more likely to kill themselves, but the suicide is not accounting for the premature mortality. It's primarily heart attacks, diabetes, obesity, and other complicating illnesses. So why? Why is this happening? The World Health Organization looked at this and they identified three broad categories. They said it's related to individual's behavior. So that means the mentally ill are overeating or under-exercising. It's their lifestyle behaviors. Or maybe it's due to factors related to their disorder. It's these medication side effects. They also identified problems at the health system level. Maybe the mentally ill aren't going to their primary care doctors and doing what they're supposed to do to take care of their health. Or maybe it's wider societal issues. People with chronic mental illness are more likely to be unemployed and have limited social resources, which are independent risk factors for premature mortality unto themselves. What I'm going to assert in the rest of this presentation is I think we as a field have been missing the elephant in the room. We are ignoring really crucial, important information. I want to start with this question. What causes mental illness in the first place? If mental illnesses are associated with premature mortality and all of these metabolic disorders, what causes it? At this point, the answer, the real answer, if you talk to the leading neuroscientists and psychiatrists, is no one knows. It's too complicated. All we know are risk factors. And what are the risk factors? We usually lump them into the biopsychosocial model. We say that there are biological factors, psychological factors, and social factors that all come together to play a role in mental illness. Now, this applies to all mental disorders, including schizophrenia and bipolar disorder. Even though most people think of those as biological disorders, it turns out that psychological and social factors, such as abuse in childhood, do in fact play a role in the development of schizophrenia and bipolar disorder. It's not just genetics. I am here to ask a big picture question. Could metabolism be the elephant in the room that we have been missing all along? That begs the question, well, what is metabolism? Metabolism is more than just burning calories. And it's more than obesity, diabetes, and cardiovascular disease. In fact, it's the process that all living organisms use to convert food into energy or building blocks that are used to maintain or grow cells. And the definition also includes the effective management of waste products. In fact, metabolism is fundamental to the definition of life. And so in that sense, of course, mental disorders are related to metabolism. In essence, everything is. But in fact, we have decades of basic science research and neuroimaging research documenting that people with mental disorders have metabolic disturbances in their brains and in their bodies. These include schizophrenia, bipolar disorder, anxiety, PTSD, depression, alcohol use disorder. And what do I mean when I say metabolic disturbances? I mean, higher levels of lactate. There's something called the ATP to ADB ratio, reactive oxygen species, redox markers, levels of NAD to NADH, inflammation, cortisol. Most of you have heard of insulin and most people think of insulin as it relates to diabetes. But in fact, insulin receptors are located throughout the human brain and are critically important to brain function. And in fact, abnormalities of glucose metabolism are often seen in people with first episode non-treated bipolar disorder and schizophrenia, as I already mentioned. And mitochondrial dysfunction has been found in many psychiatric disorders. And in fact, this may be fundamental to the pathophysiology of mental illness because these metabolic problems often come first. So this first bullet looked at a longitudinal group of population survey of women, women with polycystic ovary syndrome, which is highly related to obesity and to diabetes and insulin resistance. They had an eightfold increased risk of developing subsequent bipolar disorder compared to those women who didn't have it. And in fact, metformin use, so managing these high levels of blood sugar, decreased this risk. Another longitudinal study of over 5,000 children followed them from age one to 24. And what they found is that those beginning at age nine, the children with the highest levels of insulin resistance were five times more likely to have psychosis at risk mental state. And they were three times more likely, this is 300% more likely to already be diagnosed with bipolar disorder or schizophrenia. So insulin resistance seems to come first and then leads to serious mental illness. And now I'm going to talk about the ketogenic diet, which I call not a diet, but a metabolic treatment. So what is a ketogenic diet? It's a diet that's high in fat, low in carbohydrate and moderate in protein. It was developed in the 1920s by a physician for the treatment of epilepsy. A lot of you probably have heard of the keto diet as a weight loss diet. This is actually a 100 year old treatment for epilepsy. It results in the body using fat instead of carbohydrates. Ketogenic basically means the production of ketone bodies from fat. So it basically means that your body, instead of running primarily on carbohydrates as a fuel source, it starts using fat and ketones as fuel sources. There are three types of ketone bodies, beta-hydroxybutyrate, acetoacetate, and this thing is hiding my thing. So well, anyway, these ketone bodies are measurable in blood, breath, and urine. So clinicians and individuals can objectively test for compliance. So one of the things I love about doing this diet is that I can tell whether somebody's actually doing the diet or not. I don't have to take their word for it. I can measure whether they're doing it. Most people will lose weight on a ketogenic diet, but people can maintain weight or even gain weight on this diet. So one of the big teaching points I want to make is that there are a lot of variations of the ketogenic diet. You'll hear keto diet, and it really means a lot of different things. The classic ketogenic diet that was developed 100 years ago is usually referred to as a four to one or three to one ratio diet. And what does that mean? It means four grams of fat for every one gram of everything else. And I'll show you a picture of what that means, but there's fasting and intermittent fasting. You can add medium chain triglycerides to a ketogenic diet, and that can increase the level of ketones. There's the Atkins diet. There's low carb, high fat diet that are usually weight loss diets, and there are lots of others. But let me give you a sense, because if I say four to one ratio diet, most people don't know what that means. So let me give you a sense of what that means. If you look at these four plates, they all contain meals, and they all contain the same ingredients and they're the same number of calories. So if you look at the green plate, this is what most people would think of as a standard kind of low carb meal. It's chicken breast, broccoli, a little ramekin of mayonnaise, and then there's a splash of olive oil somewhere in there. The red plate, same number of calories, same ingredients, has chicken breast, broccoli, but now you've got the ramekin of mayonnaise, and you've got a syringe of olive oil, and you have to consume all of that. That's what the four to one ratio diet looks like. The syringe is a really important symbol, because this is not a weight loss diet. The four to one ratio diet is a medical prescription. It is for brain disorders, and you don't do this for weight loss. What else can you eat? Because a syringe of olive oil is not very appetizing. In fact, you can make this really appealing. You can have steak, salmon, coconut in the form of coconut cream or coconut milk, butter, olive oil. Some people have bulletproof coffee, eggs and bacon. You have low carbohydrate vegetables like spinach, high fat fruits like avocados. You can get creative and make pizza. You can even make keto ice cream. Now I want to tell you the story of the ketogenic diet for epilepsy. It turns out that fasting has been used in the treatment of epilepsy since the time of Hippocrates. For a long time, this was largely thought to be religious folklore or nonsense. In 1921, Dr. Galen reported the use of intermittent fasting to treat a child with epilepsy and lo and behold, it worked. That same year, the problem with fasting as the treatment is that you can only fast people for so long and then they start starving to death and that's not a very good treatment. So it was the ingenious Dr. Russell Wilder at the Mayo Clinic who developed the ketogenic diet and he did it for one specific reason. He wanted to see if he could trick the body into thinking that it was fasting, but provide the body with enough nutrition and nutrients and vitamins so that it could grow and thrive and not go into starvation. And he did it with one goal, to try to stop seizures in people who had epilepsy. And lo and behold, it worked. Early results were really impressive. 50% were seizure-free and another 35% were markedly improved. But by 1950, this fell out of favor because taking an anti-epileptic medication is so much easier than doing this diet. But lo and behold, it was rediscovered in the 1970s at Johns Hopkins because 30% of people with epilepsy even today do not respond to any of the medications or treatments we have to offer. And so it was really due to Jim Abrams and the Charlie Foundation that created publicity for this. We now have over 100 ketogenic diet centers around the world, and we have a lot of evidence for this. There's a Cochrane Review, which is the gold standard meta-analysis in the medical field. So a Cochrane Review done in 2020, 13 randomized controlled trials and over 900 participants. At three months, seizure freedom rates in children were as high as 55%. And this is in children who have treatment-resistant epilepsy. So they've already tried lots of medications and none of them have worked. Some of them had even had brain surgery and that didn't work. And then they try this diet and 55% of them can become seizure-free with this diet. Now in the research studies, no adults achieve seizure freedom, but that's largely because researchers have a hard time getting adults to do this diet. There are cases of adults who are seizure-free. Another 30% or so get a reduction in seizures. You'll notice this is not 100%. This is not a panacea. It is not a miracle cure for treatment-resistant epilepsy, but it does work in a very large percentage of people. So how does this work? How does a diet stop seizures? It turns out that we actually know more about the effects of this diet on the brain than we do any other dietary intervention. And that is shocking to most people. The reason it's true is because neurologists, neuroscientists, even biotech companies have been studying this diet for decades, trying to figure out how does it work? Like this diet is stopping seizures when some of our best pills don't. What is this diet doing? I am not going to go through this complicated graph. Instead, I've broken it into easy to understand bullets, but I want you to understand that every one of these bullets is supported by a lot of evidence in literature and clinical trials in the medical literature. So this diet lowers blood sugar and insulin levels. In other words, it improves insulin resistance. And I already told you why that might be key for people with mental illness. It produces ketone bodies, which are an alternate source of energy instead of glucose. Ketone bodies themselves have anti-seizure effects. It changes neurotransmitter systems, including GABA, glutamate, and adenosine, as well as calcium channels and other channels. It increases mitochondrial function and production. It increases polyunsaturated fatty acids, which are neuroprotective. It increases satiety through the leptin system. It decreases brain inflammation. It changes the gut microbiome in beneficial ways. It actually changes gene expression in your cells. And it increases these last three, increasing autophagy, increasing NAD, and activating sirtuin genes are all thought to be an anti-aging effect. So those are some pretty powerful effects. And in reality, this diet is being studied for a lot of medical conditions. And here is a list. So right now there are case reports and or large clinical studies of the ketogenic diet for all of these conditions, weight loss, obesity, but all of these other things. But what I want you to take away from this slide is not that the ketogenic diet is a miracle cure for all of these things, because it is not. I will be the first to tell you, it is not a miracle cure. It is not going to cure amyotrophic lateral sclerosis. It is not going to cure brain tumors, but it is a treatment that is being used in all of these conditions, and at least has been shown to have some beneficial effects for all of them. So let's talk about mental health conditions. Why should we even think about the ketogenic diet for mental health conditions? Well, first, the ketogenic diet is an evidence-based proven treatment for epilepsy. Many of its known mechanisms of action address known problems in people with mental disorders. We know about these metabolic disturbances in the brains of people with mental disorders, and the ketogenic diet can address those metabolic problems in the brain. It turns out many treatments for epilepsy are used routinely in the treatment of psychiatric disorders. Some of them are FDA approved, but many are not. So this includes medications like Depakote, Tegretol, Lamictal, Topamax, Neurontin, or Gabapentin, and all of the benzodiazepines, Valium, Klonopin, Xanax, Ativan. All of the meds I just listed are anti-seizure medicines. And it turns out that off-label treatments for psychiatric disorders are very common. If any of you have heard of the use of Neurontin or Gabapentin, that is 100% off-label in all mental disorders. We don't have evidence that it works for any mental disorder. It does not have an FDA indication for the treatment of any mental disorder, yet we use it in tens of millions of people. And we use it because our standard treatments fail to work for far too many people. Therefore, I believe it is not unreasonable to consider using the ketogenic diet in people with treatment-resistant mental disorders. So do we have any evidence that it actually works? Well, with depression, the evidence is growing but very weak right now. We have some weight loss trials showing that people who got a ketogenic diet had improvement in depression symptoms, but at the same time, they were also losing weight. We also have numerous studies in the epilepsy literature showing that people who are using this diet for their epilepsy also had sometimes significant improvement in their depression symptoms, but the confound in that is that, well, their seizures were probably getting better at the same time. And so everybody says, well, wouldn't you feel better if your seizures were getting better? Maybe it's not really an antidepressant effect. Maybe it's just an antiseizure effect and that is impacting their mood. Alcohol use disorder, this may be shocking, but this study was actually done at the National Institute of Alcohol Abuse and Alcoholism, led, is a senior author by none other than Nora Volkow, who is the director of the National Institute of Drug Abuse. So it turns out that people with alcohol use disorder have metabolic problems in their brain. Their brains, parts of their brain or areas in their brain have trouble using glucose as an energy source. And animal models have demonstrated reduced alcohol intake in rats. And so these researchers at the National Institutes of Health recruited people with alcohol use disorder, brought them into a detox center and assigned half of them to a ketogenic diet and the other half to the standard American diet. And they went through a usual detox protocol. And what the researchers found was that the people who got the ketogenic diet needed fewer benzodiazepines for their detox. And nonetheless, even though they got less medicine, they had fewer withdrawal symptoms from alcohol. They also reported fewer cravings for alcohol. And when they did brain scans, the researchers found that their brain metabolism was improved in the areas that they were targeting and levels of brain inflammation were reduced on the ketogenic diet. So schizophrenia and bipolar disorder. This is actually probably the most exciting emerging area for serious mental disorder. As all of you probably know, schizophrenia affects about 1% of our population, bipolar disorder, anywhere from two to 5%. There is a lot of overlap in symptoms between these diagnoses and some people, some experts are saying that these are a spectrum disorder. And as you also probably know, current treatment outcomes are poor. This longitudinal study following over 6,000 patients diagnosed with schizophrenia found that with standard treatment, only 33% got long lasting symptom remission. Only one quarter had adequate quality of life. Only 13% were able to work or go to school. And if you put those all together and call that a recovery, only 4% of people with schizophrenia get a recovery based on our current treatments. So clearly we need new ideas and new ways to think about and potentially treat these disorders. Is there any evidence that the ketogenic diet might play a role? Well, we have these four, I'm not gonna read through all of these details because I do wanna leave some time for question and answer, but you've got the slides. So if you wanna read up more on any of these, you can. But the first four bullets are all animal studies. So they're animal models that we would, the same animal models that we use to develop antipsychotic medications. And they all found that the ketogenic diet was just as effective as an antipsychotic medication. One of them actually compared it directly to olanzapine and it was just as effective as olanzapine in terms of its antipsychotic effects. The human trials actually go back to 1965 when they did a pilot study of the ketogenic diet in schizophrenia and 10 women who are hospitalized. And the researchers reported that the women getting ketogenic diet had improvement in symptoms after two weeks, but that when they stopped the diet, some of the symptoms started coming back. We have these additional studies. And again, I'm not gonna go through all of these. These next three studies, these are case series and the middle one is a small pilot trial that I conducted with researchers in Ecuador. So we can actually potentially use this treatment in even impoverished areas. But instead of going through the details of these cases, I wanna tell you a story. I wanna tell you the story about the elderly woman that you see at the bottom of the screen. That is not her real picture, but she gave me permission to use her real name and her real name is Doris. And I wanna tell you her story. So Doris was diagnosed with schizophrenia at age 17. And she had schizophrenia in every sense of the word. She had daily hallucinations and delusions. She was frequently paranoid. She was tormented by her illness. She tried numerous antipsychotic, mood stabilizing, antidepressant and other medications. She was in and out of hospitals and nothing was working. She had a guardian, because she couldn't take care of herself and she had a PACT team. She had gained an enormous amount of weight and she weighed 330 pounds. She got to the age of 70. Between the ages of 68 and 70, she tried to kill herself at least six times. She was hospitalized because she hated her life. She hated everything about it. Her doctor recommended that she go to a weight loss clinic because she was so overweight. And so she went to the weight loss clinic at Duke University, where they happened to be using the ketogenic diet as the weight loss treatment. She started the ketogenic diet and within two weeks, spontaneously noted that her hallucinations were going away. When I spoke with her, she actually said, after about a month, she was dumbfounded because for the first time in decades, she could hear the birds chirping and the birds chirping and the birds chirping. She could hear the birds singing outside because the voices weren't drowning them out anymore. After six months, Doris was able to get off all her medication. She stopped seeing mental health professionals. Within a couple of years, she was able to get rid of the guardian and the PACT team. She learned how to take care of herself. Doris lived for an additional 15 years. She lived to the age of 85 and she remained in full remission from her schizophrenia without any medications, without any mental health professionals and without any hospitalizations. Now that is one case. In the two cases that I presented at the bottom, there's another case, somebody who had psychotic symptoms for 20 years. The reason I tell this story is not to promote false hope, not to say that what was a miracle cure for Doris is going to be a miracle cure for everybody with this disorder, but there are other people exactly like Doris who are having similar results. She is not alone. And in the case that I reported in the medical literature, she was not alone. And I believe it offers really important insights into what is causing schizophrenia to begin with. And it opens up entirely new ways to think about treating these illnesses. The largest case series was just published in the last month. This was a case series of, they reported on 28 patients. The real answer is that 31 patients were selected by the psychiatrist in France, admitted to the hospital to try the ketogenic diet. Three of the patients did not want to stay on the diet after a week. So they left the study. So we need to take that into account. 10% of the people who tried to start this diet did not do it. Of the remaining 28 patients who were able to successfully stay in the hospital and do the diet, they included 12 people with bipolar disorder, six with chronic depression, chronic treatment resistant depression, and 10 with schizophrenia. And the reality is that many of them, 100% had at least some degree of improvement in symptoms of those who did it. So again, that would be 90% of the total comers. 40% of those who did it did not have symptoms. But 43% by diagnostic assessments achieved clinical remission. Almost all the patients lost at least a little bit of weight and 64% of the patients were discharged on less medication than they came into the hospital for. So it wasn't that the hospital was adding more medicines to make them better. They were actually reducing their medicines. So what if you are a mental health clinician and you're thinking, I might wanna use this treatment, or if you are somebody who suffers from a mental health condition or a family member, first and foremost, I wanna tell you very clearly and straightforwardly, do not do this on your own, please. I really mean that. This isn't like the warning of the doctor saying, don't exercise on your own before you get a thorough checkup. This is a real warning. And why do I say that? Because when in the first two to four weeks, there's something called keto adaptation or keto flu, where your body is going through dramatic shifts in metabolism. And for some people, this can be extraordinarily uncomfortable, but in people with serious mental illness, it can be dangerous. And I have seen it be dangerous. I am a psychiatrist. I know how to manage symptoms. So I have managed it. I don't wanna scare people, but just like a medication can sometimes be dangerous. Some medications can cause horrible side effects or mild side effects. Some medications can cause you to not sleep. Those need to be managed by a competent mental health professional. The ketogenic diet is just as powerful as a medication. I've seen some people develop insomnia. Some people can get worse depression before it gets better. Because of the insomnia, I have seen some people actually get manic or hypomanic from it. And if they already have preexisting psychotic symptoms, those symptoms can get worse in my mind, probably because they are sleep deprived. And the strategy that I use in managing that is to help that person get adequate sleep. I don't always stop the diet. Sometimes I do, but I try to manage the sleep. And usually if I can get the person sleeping, they do okay. Hypomania and mania are common and often unrecognized, but psychiatric medications need to be managed. Some people need these. If you are gonna try to reduce your meds, that needs to be done extraordinarily carefully and gingerly with the supervision of a competent professional. That is extraordinarily dangerous to try to change your meds on your own. So please, please do not do that. I'm warning you now. Please do not do that. And treatment includes more than just the diet. A lot of people end up staying on medications or needing medications, maybe even needing sleep medications to help them through that keto adaptation. But they need sleep. They need a daily routine. They need exercise. They need maybe psychotherapy, stress management. If they're using drugs and alcohol, guess what? They need to deal with that too. The ketogenic diet isn't miraculously going to provide all of these services and therapeutic modalities. So if you wanna try the ketogenic diet as a treatment, what do you need? I argue you need two things. You need a competent mental health professional, preferably a psychiatrist or psychiatric nurse practitioner. Why do I choose those two? Because they are prescribers. They are the primary prescribers in psychiatry. And most people with serious mental illness are on medications. And so we need somebody who knows how to manage psychiatric medications to help manage this treatment because this treatment is like a medication. And you also need a competent ketogenic diet clinician. So this can be a dietitian. And so if you're a mental health professional and you wanna think about trying this treatment, with one or more of your patients, I would highly encourage you to partner with a ketogenic dietitian. That person will manage the ketogenic diet part of it. They'll do the education. They'll do monitoring. They'll even tell you what labs you should be checking for safety. They'll recommend vitamins and supplements that might be needed. And you can do the mental health piece. Optional additions include maybe a keto coach or a keto food service. If you are a mental health clinician, I'm gonna strongly recommend that you carefully manage your medical record documentation in these ways. I'm not gonna read through them all. But again, this is a treatment for treatment resistant. Right now, the state of the art, it is an evidence-based treatment for epilepsy. But the reality is we use epilepsy treatments off-label in psychiatry every day in tens of millions of people. And so I believe it is not unreasonable to consider trying this as an off-label epilepsy treatment in treatment-resistant patients. This does not replace first-line treatment. People need to try standard treatments first, at least three or more. But if they have failed those standard treatments, I think clinicians and patients together can at least discuss this as a possible option, given that we use epilepsy treatments all the time. And you can download that slide if you are a clinician and you want more details. But so the reality is people in the mental health field and the neuroscience field are extremely excited about this. We have research on schizophrenia, bipolar disorder, depression, Alzheimer's disease, PTSD, alcohol use disorder, opioid use disorder, and autism being conducted at some premier facilities, including the National Institute of Health. And we have at least five controlled, randomized controlled trials of the ketogenic diet for schizophrenia and bipolar disorder getting underway right now, today. So more research is coming, so stay tuned for that. And that will hopefully help inform whether this treatment actually makes it into mainstream mental health treatment or not. So I've got lots of references for you. Believe it or not, there is a ton of evidence for everything that I have just shared with you. And with that, I will stop and thank you for your attention. Dr. Palmer, that was fascinating. Side note, as someone who is currently caring for a father in end-stage renal disease from diabetes and high blood pressure, fascinating information. One of the slides that people will see is one that provides some additional information about Family Meals Awareness Month, which is happening in September. And one of the files there, the infographics that are in the handouts are some information about that month and about what that effort is about, that regardless of who you consider your family, just some of the, you mentioned the biopsychosocial approach, Dr. Palmer, it's some of the social component of meals as well. So we also want you to be aware that you can have access. Before we get into the Q&A, I wanna take a minute to let you know that SMI Advisor is available for your mobile devices, and you do see the app slide that's up there. Use the SMI Advisor app to access resources, education, and upcoming events, and you can complete mental health rating scales, and you can even submit questions directly to the clinical expert team on the SMI Advisor project. And you can download the app now at smiadvisor.org. We'll move on into Q&A right now. One of the first questions we got was how can you tell when a medication might be preventing recovery during use of the diet? It's a really important question, and right now we don't have clear clinical guidance on this question, but as I mentioned, and as I think most of you know, a lot of antipsychotic medications in particular, we know that they contribute to weight gain, that they are, again, this is not me being antipsychiatry or me being anti-medication. These are warnings on the FDA package inserts. These medications cause weight gain, they can cause insulin resistance and type 2 diabetes, they can cause premature cardiovascular disease, and in the elderly, they can cause premature mortality. Those are all on the package inserts. Unfortunately, those are acting against what we're trying to do with the ketogenic diet. When we are trying to improve brain metabolism, we're trying to improve insulin sensitivity. We're trying to improve metabolism broadly so people are a normal, healthy weight, and so that their appetite system and metabolism are appropriate to maintain a normal, healthy weight. Certainly, we wanna prevent premature heart attacks and premature death. Right now, we don't have clear guidance and we don't have enough clinical information. I will tell you that, we don't. But some of the patients in the case reports and case series have been able to get off all their medications. Again, that needs to go very, very gradually and slowly. I can tell you now, one of the patients I discussed, I wrote up in one of those case series, she got dramatically better on a ketogenic diet and took it upon herself to abruptly stop all 14 of her prescribed medications. And that was a disaster. It was a disaster. She ended up hospitalized for two months because of that. So this is something clinicians and patients will have to work out. If you do need to manage your medications, they need to be very, very slowly and cautiously adjusted. I very much appreciate that response, Dr. Palmer. And can't emphasize enough, I had written it down when you said it and highlighted it multiple times. Don't do this alone. Whether it's, anytime you're making changes in your treatment regime, specifically the biological components of it, it is so critical to involve all the players in your treatment team so that everybody knows what's going on with you. And I would think that would include your primary care physician as well, not just your psychiatric treatment team. Yes. Go ahead, I'm sorry. No, I think that if you can involve your primary care doctor, absolutely, I'm all for it. I think as we all know, a lot of patients with serious mental illness, that's one of the World Health Organization bullets that they identified, is it's hard to get these people to their primary care doctors, sometimes because of their symptoms. They're hallucinating, they're paranoid, they're afraid. They don't wanna go out in public. They don't wanna go to a primary care doctor who's gonna poke and prod them. And so it's not about blaming, it's not about shaming. And sometimes the psychiatrist or psychiatric nurse practitioner is the medical professional who's going to have to help manage some of this because it can be difficult to get them to their primary care docs. But if we can include the primary care doc, I'm all for it. Right, they're complicated illnesses, right? The serious mental illnesses are so complicated. Another question is, is there data on how people react if they slip out of ketosis? Either for just a day or two, do psychotic symptoms resurface? They do. It depends on how long the person has been on the diet. And so what we know from the epilepsy literature, and then I'll share with you what I've seen in the mental health experience. What we know in the epilepsy literature is that when in the first six months, when people start this diet, even if it completely stops seizures, and it can do that in people who have been having 100 seizures a day, it can completely stop their seizures. But in the first six months, if they stop the diet, those seizures will come back right away with a vengeance often. And within 24 hours, that person can be seizing. And that's why I say the ketogenic diet really is more, it's not a diet, it is like a medication. It is like you are changing your body and brain metabolism just like a medication might, and that has powerful effects. And so you can't have cheat days if you're using this as a therapeutic intervention. If you're just trying to lose weight, sure, you can have cheat days. It doesn't matter if you gain a pound or two over the weekend because you cheated. But if you're using this to control serious symptoms that are disabling or can be dangerous or just cause a lot of suffering, you really should not be cheating. And I have seen the same experience in patients with serious mental illness. For example, one patient of mine who was doing extraordinarily well on the diet and he went off the diet, because he was feeling so much better, he figured he could. And so he went off the diet and had pizza and he was debilitated, crippled by hallucinations, depression for three straight days, could barely get out of bed. It was awful. It was as though he stopped his antipsychotic medication. The good news with the ketogenic diet is that once people have done it for anywhere from two to five years, a lot of people with epilepsy are able to stop it after two to five years and remain seizure-free. So it's not necessarily a lifelong treatment. The diet allows the brain in some ways to kind of heal itself, if you will, by restoring brain metabolism, it allows some healing to take place. And in some people, not all, but in some people, they can stop the diet successfully, but it has to be after like two to five years. So if you're trying this intervention, the first six months, you really need to be committed to doing it, at least trying your best. And it sounds like the critical point to keep reminding ourselves of is this is a treatment, as you said, not just a diet. It's a treatment. I think we've got time for one more question. There's a lot of overlap in the genome-wide association studies of mental disorders. Could this be genetic similarities or could there be genetic similarities in metabolic disturbances? Yeah, it's a great question. And there are genetic similarities. There are. They don't get talked about as much, but we know that, so for instance, there are some rare disorders that affect mitochondria, and mitochondria are central to metabolism in your cell. They are like the powerhouse of the cell. That's what most people know them as. They're actually a lot more than that. But people who have these rare mitochondrial genetic defects, they are about 20% of them get diagnosed with bipolar disorder. So hands down, that is the single highest risk genetic defect for developing bipolar disorder is having a mitochondrial genetic problem. But lots of others. So again, this connection between diabetes and serious mental illness, which includes schizophrenia and bipolar disorder and even chronic depression, we have known since the 1800s that those illnesses run in the exact same families that diabetes runs in. So diabetes, obesity, and serious mental illness run in the exact same families. One of the big questions is whether it's all genetic and genes or whether those might be epigenetic mechanisms of transmission. So it turns out that we can actually, parents can transmit information to their children, not just through genes per se, but through epigenetic mechanisms. And it's increasingly looking like those might be the more significant ways that these disorders are getting transmitted. Fascinating. It really is fascinating. One more question because this just came through and this is one I'm curious to hear what your opinion is. You mentioned several different types of ketogenic diets. Which version do you use in your clinical practice for mental health issues? It's a really important question. And the way that I look at it is the ketogenic diet is like a medication. And so I think about it as kind of like, I think about your question is what's the starting dose? The real answer is with any medication, we might use a different dose. We will start with something, but we might need to increase it. Maybe we decrease it because the person doesn't tolerate it. And so what's the starting dose? And the starting dose that I typically use is either a two to one ratio diet, if you think about it in that way, or the easiest way to think about it, and you can actually look this up. And this is an evidence-based treatment for epilepsy. They've studied it at Johns Hopkins and other places. If you look up the modified Atkins diet, so that is a version of the ketogenic diet where it's actually fairly easy. It's easy to monitor. It's easy to think about like, what am I gonna be eating? You don't have to weigh and measure anything. You don't have to be precise in what you're eating. But the modified Atkins diet is usually what I start with. If people get significant benefit, but they don't get all the way better, then I actually get much more sophisticated. I start measuring their ketone levels, and I might tweak the diet. I might increase the dose, so to speak, and ask them to try a three to one ratio diet where we actually do get a little more meticulous and weigh and measure, or at least just pay attention to see if we can increase ketones. And in reality, in many cases, I've had tremendous success with that approach. Sometimes people get 50% improvement on the modified Atkins diet, but then when we go to a three to one ratio diet, they can get like 95% improvement. They're getting close to a remission. But it's in the early stages. We've got five randomized controlled trials. Hopefully those will help inform these questions. These are really important and good questions, but don't take my word for it because I have just limited clinical practice right now. But so fascinating. And at NAMI, we are all about hope and that people are looking for newer and better treatment. So this is promising. So again, Dr. Palmer, thank you so much. And if you don't, whoever's clicking the slides, not sure if it's you or someone else now, but if you can go to the next one, I wanna remind the people who have joined us that if there are any topics covered in this webinar that you'd like to discuss with colleagues in the mental health field, you can post a question or a comment on SMI Advisors Webinar Roundtable Topics Discussion Board. This is a super easy way to network and share ideas with other clinicians who participated in the webinar. If you have questions about this webinar or any other topic related to evidence-based care for serious mental illness, you can get an answer within one business day from one of SMI Advisors National Experts on SMI. The service is available to all mental health clinicians, peer support specialists, administrators, and anyone else in the mental health space who works with people who have serious mental illness and it's completely free. I promise it's completely free and a confidential service. Next slide. SMI Advisor is just one of many SAMHSA initiatives that are designed to help clinicians implement evidence-based care. We'd encourage you to explore the resources available on mental health addiction and prevention TTCs, as well as the National Center of Excellence for Eating Disorders and the Suicide Prevention Resource Center. These initiatives cover a broad range of topics from school-based mental health through the opioid epidemic. And then next, claiming your credit. To claim your credit for participating in today's webinar, you'll need to have met the requisite attendance threshold for your profession. Verification of attendance can take up to five minutes and you'll then be able to select next to advance and complete the program evaluation to claim your credit. And let's look now at the upcoming webinar slide. We'd like for you to think about joining us on August 12th as Dr. Edgar Ramos presents assessment and clinical understanding of aculturative stress on severe mental illness within the Latinx community. This webinar is free and will be held August 12th from 12 to 1 p.m. Eastern time, and that's on a Friday. We wanna thank you for joining us in this presentation and Dr. Palmer, again, thank you so much for giving us insight into this treatment option. Until next time, everyone take care.

webinar

metabolism

mental health

ketogenic diet

epilepsy treatment

bidirectional relationship

depression

schizophrenia

bipolar disorder

treatment option