Diet & Nutrition for Mental Health | Dr. Chris Palmer

welcome to the huberman Lab podcast where we discuss science and science-based tools for everyday [Music] life I'm Andrew huberman and I'm a professor of neurobiology and Opthalmology at Stanford school of medicine today my guest is Dr Chris Palmer Dr Chris Palmer is a medical doctor specializing in Psychiatry at Harvard Medical School he is the world expert in the relationship between metabolic disorders and psychiatric disorders he treats a variety of different condition including psychosis including schizophrenia as well as attention deficit hyperactivity disorder obsessive compulsive disorder anxiety disorders and depression among others he is best known for understanding the relationship between how metabolism and these various disorders of the Mind interact and indeed today he describes not only his own fascinating journey into the field of Psychiatry but also his clinical and research experience using diet that is different forms of nutrition in order to to treat various psychiatric disorders he describes some remarkable case studies of individuals and groups of people who have achieved tremendous relief from the types of psychiatric disorders that I just mentioned a few moments ago as well as new and emerging themes as to how metabolism and the mind interact to control things like obesity indeed he raises the hypothesis that perhaps obesity in many cases is the consequence of a brain dysfunction as opposed to the consequence of a metab metabolic dysfunction that then impacts the brain during today's episode he shares with us his overriding hypothesis about the critical roles that mitochondrial function and dysfunction play in mental health and mental illness and how various particular types of diets ranging from the ketogenic diet to modified ketogenic diet and even just slight adjustments in carbohydrate intake can be used in order to change mitochondrial function and bring relief for various psychiatric illnesses he also highlights the essential and important theme that various diet interventions including the ketogenic diet were not first developed for sake of weight loss but rather were developed as treatments for neurologic conditions such as epilepsy today he shares with us how the foods that we eat alone and in combination and how fasting both intermittent fasting and more lengthy fasts can interact with the way that our brain functions to strongly control the way that we think feel and behave what's wonderful is that Dr Palmer Not only explains the science and his clinical expertise but also points to various actionable measures that people can take in order to improve their mental health I'd like to mention that Dr Palmer is also the author of a terrific new book the title is brain energy a revolutionary breakthrough in understanding mental health and improving treatment for anxiety depression OCD PTSD and more I've read the book and it is a terrific read I came away from this book with a much evolved understanding of how the various psychiatric disorders that I just described as well as ADHD emerge in people and it has completely revised my understanding about the possible origins of various psychiatric disorders and the best ways to treat them including both with medications but also with nutritional approaches if you'd like to learn more about Dr Palmer's work and the book please go to chrisp Palmer md.com we also provide links to the book and to his website in our show note captions before we begin I'd like to emphasize that this podcast is separate from my teach in and research roles at Stanford it is however part of my desire and effort to bring zero cost to Consumer information about science and science related tools for the general public in keeping with that theme I'd like to thank the sponsors of today's podcast our first sponsor is thesis thesis makes custom neut tropics and as I've said many times before on this podcast I am not a fan of the word neut tropics because it means smart drugs and 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I'm really excited about this topic because I think most people know what mental illnesses or they have some idea what that is most people have some idea what nutrition is fewer people certainly know how closely those things can interact and I think everybody is familiar with the feeling of a food or the ingestion of a food making them feel good in the short term and we eat a food that tastes delicious to us or that we associate with something nice and we feel good mentally and physically whereas when we eat something that gives us food poisoning or maybe even something that just doesn't taste that great or that we associate with a bad experience we feel less good in the short term but I believe that very few people understand or are familiar with the fact that nutrition and our mental health interact in this very intimate maybe even causal way and that is something that occurs over long periods of time meaning what I ate yesterday the day before maybe even 10 years ago could be impacting the way that my brain and body are making me feel now so if you would I'd love for you to just tell us about a little bit of the the history in particular your history with exploring the relationship between nutrition and mental health and then we can dive into some of the um more particulars of ketogenic diets versus other diets and some of the truly miraculous findings that you and others are are coming up with um based on real patience and real experiences of people who suffer and then find Relief by altering their nutrition sure I you know I this story really starts with my own personal story and uh uh I don't need to go into great detail but uh to set the stage when I was a kid I definitely had mental illness started with OCD um a series of events happened in my family my mother had a horrible kind of psychotic break um and all sorts of adverse childhood events for me she and I were actually homeless together for a while um I went on to have subsequent depression suicidality all sorts of things but somehow or another I pulled myself together um and got through Medical School actually did quite well in medical school got an award for being one of the top students uh and then was doing my internship in residency at Harvard and uh and at that point in time I was diagnosed with metabolic syndrome so uh had high blood pressure horrible lipids uh and pre-diabetes and I was doing everything right supposedly I was on a lowfat diet and I was exercising regularly and year after year my doctor kept telling me diet and exercise I kept asking him what diet what exercise I was doing everything he kept telling me to do everything was getting worse my blood pressure kept going higher and uh and at some point he kind of said you're going to have to go on medication I need to put you on something for your pre-diabetes something for your cholesterol and something for your blood pressure so three pills out out of the gate and I'm like I'm only in my 20s were you overweight no technically no I had a I had a gut so you know that's a sign of insulin resistance I know now I didn't know it then but um uh and he actually kind of leaned in at one point and said you know do you do your parents have diabetes yeah do your parents have high blood pressure yeah do are your parents overweight yeah oh I'm really sorry it's genetic um basically you're screwed it's your jeans you're just going to have to bite the bullet and take Med and as a physician I knew what that meant I knew that I'm in my 20s if I'm already on three meds for metabolic syndrome I'm going to be screwed by the time I'm 40 or 50 and I'm probably going to be having heart attacks and uh and I'd heard through the rumor mill that the Atkins diet could somehow help people improve their cholesterol and pre-diabetes I actually didn't really believe it I was highly skeptical and I you know I believed everything I was taught in medical school why would why would my professors lie to me that they knew what they were talking about lowfat diet was the thing to do um and the Atkins diet was clearly dangerous and Reckless and uh but I had been trying the medical Dogma for years and it wasn't working for me and so for whatever reason I decided this is going to be my last attempt at at something different and then I'll just bite the bullet and go on meds so I tried the Atkins diet I did my own special version of it I still avoided red meat because I was terrified of red meat and you know I I I I tried to do a healthy version which is probably more like the South Beach Diet you know this was before the South Beach Diet was invented but um within three months my metabolic syndrome was completely gone so blood pressure normalized lipids normalized did your weight change or that you mentioned that you were of healthy weight but that you had a bit of um abdominal yes fat so I I lost the abdominal fat I probably lost about you know 10 pounds through this process and but everything got normal and when I went back to my doctor he was shocked he actually said what the hell are you doing during the time before you switched to this new diet uh how was your mental health if you don't mind me asking because it sound like you're very clear that there was metabol olic syndrome or you were headed towards more severe metabolic syndrome you mentioned OCD um I actually am familiar with this as a kid I had a low-level kind of Tourette's Grunt and probably obsessive still to some extent although not full-blown clinically diagnosed OCD so I can relate somewhat um if you're willing um what was the context of of all that before and after this uh nutritional switch so before the nutritional switch which I was still struggling with lowgrade depression and OCD uh I um again it wasn't necessarily interfering with my ability to function because I was functioning at a high level I mean anybody looking from the outside you're a top student you just got into one of the most competitive actually at that point it was the most competitive Residency program in the country for psychiatry so they would have looked at me and said you're fine but I wasn't I was actually on medications I was trying different medications trying to figure out how how to feel better how to stop obsessing so much how to not be so depressed um and I found that those medications they they actually came with more side effects for me than benefits I was on Prozac for a long time it totally messed up my sleep and then the psychiatrist was like you need pills to help you sleep now and I'm I I'm like that doesn't that's not really resonating very well with me and I'm now a psychiatrist I'm in my Psychiatry residency and I'm thinking you know what that's just not sitting well with me that you're going to prescribe more and more meds for all the side effects that you're causing and yet at the same time I wanted to feel better and I was learning chemical imbalances this is what we do to get rid of depression and OCD you're supposed to take your pills and so I was taking my pills I was in Psychotherapy I had been in Psychotherapy on and off for years um I had received much more intensive treatment when I was younger and that was essentially worthless for me uh it actually probably just caused harm at the end of the day psychoanalysis um various psychotherapies not psychoanalysis per se but some of them were psychoanalytically oriented psychotherapies has hospitalized at one point um uh had been put on lithium and uh imipramine which is a tricyclic anti-depressant and other things and they uh they were actually horrible they were horrible they did nothing beneficial for me um I gave them a decent amount of time to work I I really wanted to feel better um so at the time that I tried this diet I certainly wasn't impaired in the same way I wasn't struggling that much but I was still had these low-grade symptoms with trying to feel better and the thing that was the most striking to me after doing the diet for three months was not the fact that my metabolic syndrome was gone that was my goal and it was a you know seemingly miraculous uh achievement because I got rid of everything with one dietary change but the thing that I noticed was dramatic Improvement in my mood energy concentration and sleep I for the first time in my life I started waking up before my alarm went off and feeling rested that never happened to me before I I was meticulous about planning when my alarm went off and how many times I could push the snooze buttton in order to be on time for wherever I needed to be whether it was school or the hospital or whatever um I had it I had a good system I was never late for anything but uh that was shocking to me that I felt so good and you know one of the things that I've often said to people prior to the diet I always felt like there are two types of people in the world there are halves and Have Nots there are these happy peppy people who just are so positive and they've got energy and they have these the saying they like to work hard and play hard and I always understood working hard I totally got that because I was a hard worker and I understood the value of hard workor and you know you got to do something useful with yourself but I never understood who the hell wants to play hard like who's got energy for that like aren't you tired from working so hard how Earth do these people have energy to go and play hard and I assumed that they were just part of the halves in the world and they were just lucky and privileged they either had good genetics or maybe they had good good childhoods or good parents or something something that I didn't have the kids with genuine Smiles in the yearbooks yes exactly whereas the rest the rest um and by the way really appreciate you sharing some of your personal story because I think it is very important for people to hear and understand that people like yourself who are extremely high functioning and accomplished that the road was from everything I'm hearing and understanding very choppy um internally at times and that you've overcome a lot in order to get there and also have um been going through what sounds like a very long iterative process of trying to figure out what what works and what doesn't work to finally arrive at a solution and then make that the basis of much of the work that you're doing today for other people I think it's very important because I think many people share with you this notion that there are indeed two groups a happy group and Faded to be unhappy group um and it speaks to the fact that your story rather speaks to the fact that what we see is not always what's going on internally with people and that this notion of there just being two groups the the happy or the Haves and the Have Nots um can't be the way that it works and there are probably many more people suffering than we realize and that there is an important need for tools to overcome that suffering so I really just here even early in our discussion I just want to extend a genuine thanks because um so much of what I hear from people is you know questions about health and mental health and physical health but that clearly point to the fact that many people are struggling to varying degrees and even the people who are in this category of great childhood and and happiness could do far better for themselves and then also for other people so thank you for that I I want to know at the point where you realized that nutrition can play a profound role in how you feel and operate in a large number of domains you were still a student or a resident at that point I was a resident at that point did you decide that you were going to explore this in a professional context not yet okay so what was the what was the journey forward into the work that you're doing now so so the next step was that I just had friends and family who saw me saw that I had improved my health saw that I lost some weight pretty easily um in particular I remember like my sister and sister-in-law they were got really pissed at me one Thanksgiving because I could resist all the pumpkin pie and apple pie and everything else they were like how the hell are you doing that how are you resisting all of this food I said I don't crave it anymore I don't want it I'm fine I'm just I'm having turkey and green beans and and that's good enough for me so I got them to do the diet and they too noticed dramatic Improvement in their moods and energy and sleep and everything else so within a few years I I I I the the primary thing I noticed is this powerful anti-depressant effect and now I'm you know an attending physician I've got all these patients in my clinical practice with treatment resistant mental illness I'm in a tertiary care hospital so I almost never get somebody off the street with their first episode of depression out of the gate as part of my career I get treatment resistant mental disorders so I get people who've already been to six plus psychiatrists therapists they've usually tried dozens of different medications they've been in decades of psychotherapy they've often had ECT and other things and nothing's working and I'm thinking you know well we're kind of out of options for these other people and this diet is having this really powerful anti-depressant effect I think I'm going to try it and just see if any of my patients are game to try it to see if it might help them sure enough it did didn't help everyone and not everybody was interested and or able to do it but the but some of the ones who were able to do it ended up having a remarkable and Powerful anti-depressant Effect one woman actually became hypomanic within a month and she had been depressed pretty much nonstop for over 5 years chronically depressed suicidal in and out of hospitals and I saw her become hypomanic and I'm thinking wow this really is a powerful anti-depressant effect like this is amazing this is like a medication but better because it actually is working for her and um but I laid low at that point because at that point we didn't have many clinical trials of the safety or efficacy of Atkins diet for even weight loss or diabetes let alone any mental disorders and so I really actually felt like I'm On The Fringe here and this is not going to be met with with Praise by anyone so I'm just going to lay low I'm going to offer it to patients and uh and I I went along that way up until 2016 um and may just ask about the diet um when you say Atkins diet so this is low to zero starch so low carbohydrate diet certainly low sugar yeah um and was it traditional Atkins uh were you tailoring it to the individual patient depending on their psychiatric symptoms whether or not they were overweight or not overweight um I'm assuming you're not a nutritionist so how did you prescribe a nutrition plan for your patients um and what was involved in making sure that they adhered to that um maybe even some of the things you observed in terms of who was more willing to try this or not try this um any observations or maybe even data so early on I was winging at and I was you know the the the first few patients it was try this Atkins diet I want to see ketosis so I was going for ketones so they were pricking their finger and they were doing a blood Ketone test I I I didn't know about blood Ketone me monitors if they existed back then so I was we were using urine strips which are not quite as accurate but still useful as a general guide from what I understand is that right absolutely and uh so so I was strongly recommending that patients achieve urinary ketosis and the interesting thing is I noticed a pattern that when they were trying the diet and not getting ketones they often did not get a clinical benefit it was once they got into ketosis that I began to notice the clinical benefit and uh the the powerful anti-depressant effect so probably any nutrition plan AKA diet that elevated ketones in the urine to the point where you would say this person is in ketosis or they would say I'm in ketosis that was a step in the right direction independent of like exactly what they were eating or not eating to get there um including fasting at that time probably fasting wasn't as popular now thanks to the incredible work I think it's incredible and he is a former colleague and I know there's a lot of controversy about fasting but I think for many people fasting is a powerful tool for others it's a less useful tool but of Sachin Panda and others um but fasting certainly will limit your carbohydrate intake and get you into ketosis correct it will did you have any patients fast or do intermittent fasting I did um so and and we had some I had some patients who did what what Atkins had called a fat fast where they eat primarily fat um so they either fast and or they eat primarily fats to try to get in into a state of ketosis so for some patients it was actually quite easy to get into ketosis especially overweight and obese patients they have a lot of fat stores on their body and actually limiting carbohydrates usually results in high levels of ketosis for them and they probably feel better too I imagine because when we limit our starch intake we start to excrete a lot of water people can um get some pretty quick weight loss that even though it may not be fat loss makes them feel literally a little lighter maybe a little more energetic is that absolutely and uh and as the years went on you know the field was advancing more research was coming out people were getting a little more sophisticated with blood Ketone monitoring with different versions of ketogenic diets and I was evolving my practice um the thing that completely upended everything thing that I knew as a psychiatrist though was when I helped a patient in 2016 lose weight so this was a patient 33-year-old man with schizo effective disorder he had been my patient for eight years now could you clarify for be what schizo effective disorder is I I'm not a clinician but as I recall it's it's like a low level of schizophrenia so there might be some auditory hallucinations if I met this person I might think they're kind of different quote unquote weird but they would not seem NE necessarily at the um scary to me uh and to typically to other people um and I mean that with with respect of course but oftentimes people with schizophrenia can seem just like you you don't even know how to interact with them because their world seems so altered um because they have all these so-called positive symptoms hallucinations and they're talking to people that no one else can see Etc is that skizo effective so no actually so schizo effective is the same as schizophrenia essentially the only difference is it's schizophrenia with superimposed mood episodes oh so it's actually more severe than it can be okay so I have it backwards so schizo affective disorder is essentially schizophrenia and plus some mood episodes maybe I'm thinking of schizotypal schizotypal is is the lowgrade kind of mild paranoia or you know kind of eccentric beliefs and other things okay so I I uh folks out there I have my nomenclature backwards schizotypal is the quote unquote lower low schizophrenia or schizoid like um schizo effective is as or full blown schizophrenia plus full blown usually bipolar Sy and now it's absolutely clear who the clinician in the room is thank you for that reminder no no worries so so this man had schizo effective disorder he had he had daily auditory hallucinations he had paranoid delusions he could not go out in public without being terrified he uh uh he was convinced that there were these powerful families that they had technologies that could control his thoughts they could broadcast his thoughts to other people they were trying to hurt him they had targeted him for some reason he wasn't quite sure why he had some suspicions and beliefs about maybe when he did this bad thing when he was 11 years old that's why they decided to Target him this man was tormented by his illness tormented it ruined his life he had already tried 17 different medications and none of them stopped his symptoms but they did cause him to gain a lot of weight these are the medications as I recall for schizophrenia that classical ones are dopamine receptor blockers cause people to huge increases in prolactin that's why sometimes men will get breast development and they'll put on a lot of weight and they'll be catatonic or movement disorders they make you feel like I have to imagine given how good most things that release dopamine us feel that blocking dopamine receptors with antipsychotics makes people feel lousy horrible and uh and and it's a huge challenge in our field because a lot of patients don't want to take them and uh and then you get these rebound effects if patients are on them for several months and then they stop them cold turkey they can get wildly psychotic and Ill end up aggressive or hospitalized or sometimes dead um so so that's him he weighs 340 lbs and for whatever reason he gets it in his head I'm never going to get a girlfriend if I don't lose some weight he also recognizes I'm never going to get a girlfriend because I'm a loser I'm schizophrenic I live with my father I you know I have nothing going for me but I could at least try to address one of these awful horrible things about myself and maybe I could lose some weight so he asked for my help for a variety of reasons we ended up deciding to try the ketogenic diet now at this point I have no anticipation that the ketogenic diet is going to do anything for his psychiatric symptoms because this man has kizo affective disorder that's not depression depression is very different they're totally different disorders so he decides to give it a try within two weeks not only does he start losing weight but I begin to notice this dramatic anti-depressant effect he's making better eye contact he's smiling more he's talking a lot more I'm thinking like what's gotten into you like you're coming to life like you're I've never heard you talk this much I've never seen you so excited or present or alive I haven't changed his meds at all the thing that upended everything that I knew as a psychiatrist was 6 to8 weeks in he spontaneously starts reporting you know those voices that I hear all the time they're going away and he says you know you know how I always thought that there were all these families who were controlling my thoughts and out to get me and they had targeted me and I'm thinking oh yeah we've been talking about that for eight years we get to talk about that again he says you know what I now that I think about it I don't think that's true and now that I say it it sounds kind of crazy it probably never was I've probably had schizophrenia all along like everybody's been trying to tell me and I think it's going away that man went on he's now lost 160 lbs and kept it off to this day wow he was able to do things he had not been able to do since the time of his diagnosis he was able to complete a certificate program he's able to go out in public and not be paranoid he he performed improv in front of a live audience at one point he was able to move out of his father's home and live independently and that completely blew my mind as a psychiatrist and I went on a scientific journey to understand what in the hell just happened that is indeed mindblowing I'd like to take a quick break and acknowledge one of our sponsors athletic greens a letc greens now called ag1 is a vitamin mineral probiotic drink that covers all of your foundational nutritional needs I've been taking athletic greens since 2012 so I'm delighted that they're sponsoring the podcast the reason I started taking athletic greens and the reason I still take athletic greens once or usually twice a day is that it gets me the probiotics that I need for gut health our gut is very important it's populated by gut 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transition um because as we know it's not an either or medication or nutrition changes it can be both and then the other question is one of adherence you know I think about a someone with schizo effective disorder who's suffering from all the sorts of things that you described how does somebody like that organize themselves in order to stay on a ketogenic diet and I say this with all the seriousness in the world I think there are a lot of people who do not have schizotypal or schizo effective disorder who have trouble they claim um adhering to a ketogenic diet it's not the easiest diet in it certainly in its extreme form at first it's not the easiest diet to to stick to so how did he do it this sounds like a remarkable individual um and I'd also like to just know your general thoughts about um adherence to things when people are back on their heels mentally you know how do they how do they get motivated and stick to something um so the questions were medication yes or no if yes dosage adjusted yes or no and if people are suffering from depression or full-blown psychotic episodes how does one ensure that they continue to adhere to a diet so in terms of medications he has remained on medication so early on I wasn't adjusting anything I was just in disbelief and shocked that this was happening uh I didn't know what was going on over the years we have slowly but surely tried to taper him off his meds he has been on meds for decades he started medications when he was a young child his brain is has developed in response to all sorts of psychiatric medications and it has not been easy to try to get them off so we are we continue to try to get them off medication and it's challenging and difficult and I just want to say for any listener it is getting off your meds is very difficult and dangerous and you need to do it with supervision with a a a mental health professional or a prescriber um because it is dangerous when people reduce their meds too much they can get wildly symptomatic this is that true for depression as well it's true for any psychiatric medication the the brain makes adaptations in response to psychiatric medications and when you when you stop them cold turkey uh some people are fine but I wouldn't I wouldn't recommend finding out because I I've seen patients when they stop anti-depressants I've seen patients get fluidly depressed and suicidal within three months I had one patient almost quit her job because she keep she became convinced that you know well my life sucks and it's all because of my boss and I know that she's just you know a horrible human being and she's abusing me and I was like whoa whoa whoa I think this is related to your medication change we got her back on her meds within three days she said oh my God I can't believe that happened like I almost quit my job and that would have been the most illogical and irrational decision I've ever made in my entire life but somehow it seemed so real just several days ago and now that I'm back on this medication and it doesn't mean that she needs the meds but it doesn't mean that he needs the meds it means that meds need to be adjusted very safely and cautiously and gradually so that's the medication piece the adherence piece was not easy for him and for other patients it is very rare that I have a patient who I can say do the ketogenic diet come see me in three months and let me know how it's going that that almost never happens it has happened I think on two occasions but that is if I understand correctly what perhaps not you but many psychiatrists do with medication it's here's your prescription let's talk in in yes a month or three months yes um so that's a variable that is probably worth us exploring a little bit here as the conversation continues absolutely you know that frequent contact and making micro adjustments or macro adjustments to medication or nutrition could be meaningful absolutely so with that with this particular patient um you know early on he was actually pretty adherent I was seeing him once a week uh and so I could do a lot of Education I was weighing him I was checking his ketones I was checking his glucose levels you know at that point I had a blood Ketone monitor in my office so I knew whether he was compliant or not which is so beneficial in doing clinical work and research on this diet it's the only diet where within seconds I can have an objective biomarker of compliance or non-compliance uh such a key point and again brings to mind for me the parallel with medication I mean a patient can say they're taking their medication and unless they're in a hospital setting where somebody's checking under their tongue and you know all of this they they very well could not be taking it or or taking more and um you and I both know that um blood draws for neurotransmitter levels are complicated because you want to know what's in the brain and what's functional in the brain so and I have to imagine that most people there prescribed drugs for any number of different psychiatric conditions are not giving blood every time they talk to their psychiatrist or psychologist no no and when you and when we looked at you know on that front when we've looked at studies um of compliance the the majority of patients are at least somewhat non- compliant with prescription medications it's not on purpose it's it's forget they forgot they take it at night they were out late they were off their routine they forgot to brush their teeth because that's when they take their meds and so because they you know it was so late they just crashed when they got home they forgot to take their meds happens all the time if it's a medication that people take more than once a day the non-compliance rates are much higher um because it's just easy to forget so it's not that people are willfully you know disobeying their doctors or anything else it's just hard to remember to take meds consistently every day when you say um measuring ketones I um want to drill into this a little bit because it does seem that the presence of ketones and somebody being quote unquote in ketosis turns out to be the key variable certainly in your book that's what I one of the major takeaways um although there were many important takeaways um that people get into ketosis do they have to stay in ketosis so for instance I've followed the uh I don't any longer but I've tried in the past the so-called cyclic ketogenic diet where every third or fourth day you get some pasta or rice Etc um and that I it's not that was interesting um as an experiment um but to stay in ketosis uh what sort of blood levels of ketones do you like to see in your patients uh what is the range that you think most people could uh aspire to so it really depends on the patient and what I'm treating quite honestly so and I don't think every patient needs the ketogenic diet for some patients simply getting rid of junk food can make a huge difference in a mood disorder for instance so a junk food meaning highly processed food food that could last on the Shelf a very long time highly processed foods that are usually high in both sugar carbohydrate and carbs and fats those seem to be the worst foods that combination high sugar high fat um seems to be the worst combination for metabolic health and lo and behold we've got emerging data that suggests that strongly suggests it's also bad for mental health depression and anxiety are the most common mental disorders and so we have the best data for those disorders but we actually have a lot of data with even bipolar disorder and schizophrenia that insulin resistance in particular and Insulin signaling in the brain is impaired in people with chronic mental disorders kind of across the board all the way from chronic anxiety depression to bipolar to schizophrenia and even Alzheimer's disease we know that patients with all of those disorders have impaired glucose metabolism and that the insulin signaling system in the brain which is different than the insulin signaling in the periphery um seems to somehow possibly be playing a role so so to step back from that so for some patients I might just want to decrease glucose and insulin levels and I can do that by getting rid of sweets for other patients like patients with schizo affective disorder or schizophrenia or bipolar disorder especially if it's chronic if I'm using it as a brain treatment um then I do want a ketogenic diet and I usually want reasonably high levels of blood ketones usually for for depression I want to see at least greater than probably 0.8 Millo for for psychotic disorders and bipolar disorder I usually want to see levels greater than 1.5 that's what I'm shooting for if at all possible um and uh so yeah I I I think that's what I'd go for yeah so um and sorry I didn't mean to imply that you people need to be in ketosis in order to see some mental health benefits from changing their diet um you make very clear in your book and we'll go into this in more detail that avoiding insulin resistance reversing insulin resistance and essentially trying to reverse what earlier described as you know this metabolic syndrome which is a bunch of different things uh is the Target and for some people getting rid of Highly processed foods and focusing mainly on nonprocessed or minimally processed foods will really help for others going straight to the full-blown ketogenic diet will be of most benefit I'd like to back up a little bit in history and get to something which I find incredibly interesting which is epilepsy and the longstanding use of ketogenic diet and fasting to treat epilepsy and the reason I want to kind of rewind to that point in history is that I think that for a lot of listeners and people out there who are familiar with how changing your diet or changing your exercise can positively impact sleep and wait and all these things and it Cascades into feeling better that makes perfect sense but for a lot of the world still the idea that changing or using nutrition as a dissection to tool or as a treatment tool to understand and treat mental illness is still a kind of heretical idea that to them it kind of falls in the okay well that's like a woo science or something like that now obviously you're board certified physician and psychiatrist arguably one of the finest medical schools in the world Harvard Medical School you know even though I'm on the Stanford side we acknowled we acknowledge our East Coast uh you're the Harvard of the West Coast we're not going to talk we're not going to talk we're the Stanford of the East Coast that argument could go back and forth a number of times but you know this is you're you're a serious clinician and a serious scientist and uh you're you're a serious thinker but for a lot of people out there the notion of using diet they immediately think ah um well that makes perfect sense or I think there's a category of people who think well yeah didn't Atkins die of a heart attack you know I hear that a lot you know so uh like that was crazy you know like people like the immediately discard the the Atkins diet um for that reason um which I do think is throwing the baby out with the bath water but it's an interesting thing nonetheless and then I think that the majority of people sit in the middle and just want to see science and medicine come up with treatments that work and I have to say I'm very uh relieved to hear what you said earlier which was you never said that people should come off their medication and just become go on a ketogenic diet and everything will be cured you're certainly not saying that no and rather you're saying if I understand correctly that nutrition needs to be considered one of the major tools in the landscape of effective tools and that it can be very effective evidenced by the the story that you shared and and there are many other stories in there as well um of truly miraculous Transformations so let's talk about epilepsy and how the ketogenic diet is not just used for EP epilepsy but is one of the oldest if not the oldest examples of the use of nutrition to treat a condition of the nervous system that can be incredibly debilitating even deadly yeah and the reality is that this literature and this clinical history and all of the research we have was the godsend that I needed to do the work that I'm doing otherwise I would have been discredited on day one Chris Palmer's claiming that a dietary change can influence schizophrenia or schizo affective disorder that's impossible and he's a quack um but the thing that immediately got me credibility was I didn't focus on it as a diet I did a deep dive into the epilepsy literature so the ketogenic diet unbeknownst to most people was actually developed a 100 years ago 1921 by a physician for one and only one purpose to treat epilepsy it wasn't developed as a weight loss diet it wasn't developed as the the diet that all human beings should follow and the reason it was developed is because of this longstanding observation since the time of hypocrates that fasting can stop seizures now fasting is not a healthy diet fasting is the process of no diet but so we now understand a tremendous amount of science most people think going without food is bad and they equate it with starvation but in fact when we go without food it causes tremendous shifts in metabolism both brain and body metabolism and it puts the body into a mode of autophagy and conservation of resources and all sorts of things that uh that are beneficial to human health and this is why fasting has been used as a therapeutic intervention in almost every culture and almost every religion for Millennia but but for the most part that was all thought to be religious folklore that that was just crazy talk and those those stupid people way back then you know thought God cured everything and so they fasted and they just assumed that they were getting better well in 1921 one physician used intermittent fasting on a child with seizures and found that oh lo and behold this religious folklore stuff has something to it it actually worked the problem with fasting is that you can only fast for so long before you starve to death and that's not a very effective treatment and this child was ingesting water correct it was just food elimination fast food elimination so no special diet so it was but the problem with fasting for epilepsy is that as soon as people start eating a normal diet again there seizures usually come right back often times with a Vengeance and so it can be a good short-term intervention uh you know the the fasting can take a few days because it can take a few days to get ketosis um and then you can get some relief from chronic seizures but it's not a good long-term treatment because again people will starve to death as soon as they start eating seizures come back so it was actually Dr Russell Wilder at the Mayo Clinic who developed the enic diet with one and only one purpose he wanted to see can we mimic the fasting State using this special diet to see if it might stop seizures long term and lo and behold it worked it uh you know early results were extraordinarily positive 50% of patients who use the ketogenic diet became seizure-free and another 35% had a 50% or greater reduction in their seizure frequency so about 85% efficacy rate sorry to interrupt I I didn't mean to do that there the um it was it just for Pediatric epilepsy or for adult epilepsy as well so back in the 1920s we didn't have many anti-epilepsy treatments and a lot of adults were struggling as well so they were using it on anybody who would do the diet um by the 1950s Pharmaceuticals were coming out and we had many more anti-convulsant treatments and there's no question they work for a lot of people that's great and taking a pill is so much easier than doing this diet so the diet pretty much fell out of favor and nobody was using it from the 1950s to about the 70s but lo and behold even to this day people with epilepsy about 30% don't respond to the current treatments that we have available 30% will have treatment resistant epilepsy which means they continue to have seizures no matter how many anti-com volants are taking even if they've had brain surgery it just doesn't stop their seizures and so in the 1970s the ketogenic diet was resurrected at John's Hopkins for these treatment resistant cases and lo and behold it works not for all of them but it works and about uh about onethird become seizure free and these are people who've tried everything and nothing's working so one third becomes seizure-free another third get a clinical benefit meaning a 50 % or greater reduction in their seizure frequency and the other third it doesn't seem to work it's not always clear if that's because of non-compliance or if that's because the the diet's just not working but about a third a thirdd a third seizure Freedom reduction in seizures or it just doesn't work um and so the reality the the godsend for me is that we have Decades of Neuroscience research on the ketogenic diet and what it is doing to the brain we know that the ketogenic diet diet is influencing neurotransmitter levels in particular glutamate Gaba adenosine it changes calcium channel regulation uh and calcium levels which is really important in the function of cells uh it changes gene expression it it reduces brain inflammation it changes the gut microbiome and there are you know gut microbiome is a huge topic right now and there are some researchers who argue that is the primary benefit of the ketogenic diet it's changing the gut microbiome and beneficial ways um so it's doing a lot of things it obviously improves insulin resistance uh lowers glucose levels lowers insulin levels which improves insulin signaling the key for my research that I've outlined the real magic is that this diet stimulates two processes that relate to mitochondria it stimulates a process called mitophagy which is getting rid of old and defective mitochondria and replacing them with new ones and it also stimulates a process called mitochondrial biogenesis which means that after people have done the ketogenic diet for a while months or years many of their cells in their bodies and brains will have more mitochondria and those mitochondria will be healthier and I believe that is the reason the ketogenic diet is such a powerful treatment not only for epilepsy but also for people with chronic mental disorders would you mind listing off a few of the mental disorders um and I know uh this is not meant to be inside Ball but we should distinguish between psychiatric disorders and neurological uh symptoms and diseases you know that the fields of Psychiatry and neurology hopefully someday will just emerge but for instance typically if somebody is presenting with something that looks like Alzheimer's dementia they'll talk to a neurologist whereas if somebody is presenting with symptoms like schizophrenia bipolar they'll talk to a psychiatrist but if you wouldn't mind um wearing a dual hat could you just quickly list off some of the neurologic and psychiatric disorders for which ketogenic or let's just say nutrition changes have been shown to improve symptoms significantly and then maybe we can dive into a couple of these as well as get more deeply into these two very interesting aspects of mitochondrial function and repair and turnover yeah the so the field you know in terms of nutritional Psychiatry it's a broad field and it's in its infancy is the real answer if you're looking for randomized controlled trials documenting efficacy in large numbers of patients with these disorders we don't have them they're underway now but we don't have them yet what we do have our um case studies we have a lot of mechanistic um science papers by some of the leading neuroscientists and psychiatrists in the world and neurologists in the world um kind of outlining this is everything we know that the ketogenic diet is doing these are the problems in the brains of people with these chronic mental or neurological disorders so we know that they should work but but the disorders range from chronic depression to we've got we've got a trial underway for PTSD we've got one actually decent pilot trial from the National Institutes of Health for the ketogenic diet for alcohol use disorder of all things and we can go into that a little more we've got a couple of pilot Trials of the ketogenic diet for Alzheimer's disease we've got and those are randomized controlled trials we've got case studies of the ketogenic diet for chronic depression bipolar disorder and schizophrenia the largest study that we've got in that mental health sphere is a pilot study of 31 patients admitted to a French hospital um the 28 of those patients were able to do the diet and stay on the diet uh so 10% off the bat non-compliant couldn't do the diet so we need to include that but of the 28 patients who were able to do and these are 28 patients with treatment resistant mental disorders chronic depression bipolar and schizophrenia um of the patients who were able to do the ketogenic diet 100% had at least some improvement in symptoms 46% had remission of illness remission of illness that does not happen with current treatments and 64% I think were discharged on less medicine than they went into the hospital on so it wasn't that the the the people were prescribing more medicine and that's why it was they were being discharged on less medication we've got at least again a lot of the the hardcore scientists are going to say show us the randomized controlled trials with hundreds of patients and we've got five randomized control trials underway now uh funded Prim through philanthropy um I can tell you that you know we've talked about that one index patient but at this point I have now treated dozens of patients and I've heard from hundreds of patients who've been treated by other clinicians researchers or I've just heard from patients from around the world who have shared stories of complete remission of long chronic mental dis disorders like bipolar disorder and schizophrenia off of psychiatric meds some of them not all of them but some of them are able to get off all psychiatric meds and remain in remission again I think I didn't say this before but it's really important to mention for people who might be unfamiliar with the mental health field and its connection with epilepsy the reason that's it's such an important connection is that we use epilepsy treatments in psychiatric patients every day in tens of millions of people so a lot of people don't know this but I'm I'll list off some names that a lot of your listeners may have heard of and they probably know them as psychiatric drugs but in fact these are epilepsy drugs depote tegral lamal Topamax Neurontin or Gabapentin Valium clopin Xanax those are all medications that stop seizures and many of them were developed initially for seizures but we in the mental health field quickly steal them and start using them in tens of millions of people even if they're off label so that means we don't have research studies documenting that they're effective but we go ahead and use them anyway because the reality is far too many patients aren't getting better with the FDA approved treatments that we do have to offer so psychiatrists are just winging it in some cases and we're just throwing whatever we can at them and we absolutely include epilepsy treatments so in many ways using the ketogenic diet as a treatment for serious mental disorders is nothing new at all it's an established evidence-based treatment for epilepsy we use evidence-based treatments for epilepsy across the board for a wide range of mental disorders and so in many ways that's all I'm doing with the ketogenic diet it just happens to be a diet I love it I love it and I should say I love it because we had a guest on here early days of the podcast he's a colleague of mine at Stanford he's a bioengineer and a psychiatrist phenomenal scientist and psychiatrist um Carl dier off who won the Lasker prize and so so on and so forth and he made a a really important point which should have been obvious to me but wasn't um until he said it which was you know the the psychiatrist has tools just like the surgeon has tool tools but the tools are language and observing behavior um you know those are the dissection tools for what's going on in someone's brain and then as a neuroscientist you know I'm familiar with the neurotransmitters and neuromodulators and you mentioned that you know and there are these tools of of you know altering brain chemistry which are of the sorts of drugs you just listed off or anti-depressants or antis psychotics that fall into these major bins of adjusting dopamine or adjusting serotonin or some combination of dopamine serotonin epinephrine adenosine and on and on and on and it seems to me it's um it's an incredible field but that the field is still very much in its infancy that it wasn't but a hundred years ago that um people were measuring bumps on the head as a way to diagnose you know phenology and um that there's still so much to learn and so when I hear you say you know adjusting nutrition or putting people into a ketogenic state or even just eliminating highly processed food sugars Etc taking care of metabolic syndrome and then observing tremendous relief in uh clinical syndromes of or symptoms rather of psychiatric disorders it makes perfect sense to me it's yet another dissection tool and a a tool for altering brain chemistry I think that if I think about the landscape the sort of Sociology out there of uh again it there seem to be these bins like a third of people saying of course you know diet and exercise and social connection and limiting stress like that's the good stuff that's the stuff that we know really works and then about a third of people are sort of unclear and then a third of people think well if it's not a prescription drug then it just has no place in medicine and hopefully that's changing um and certainly the work that you're doing is is going to be important in in that that transition that I think we will see I'd like to talk about uh mitophagy and mitochondrial biogenesis I think um most people learn that the mitochondria are the energy um factories of cells and that indeed they are um as a neuroscientist what I know about them is that they are present everywhere in neurons not just in the so-called cell body but you can find mitochondrian in the furthest little bits of neurons and neurons can be quite big very large in fact meters long or more in some cases and some species including us depending on how tall somebody is it could be many meters or several meters rather um and that mitochondria do a a lot of stuff besides just produce energy because I think people hear mitochondria energy and they think oh so these patients felt better they lost weight they have more energy and then they're doing better but here we're talking about remission of auditory hallucinations people feeling uh Su you know suicidal and then changing their diet and feeling like life is something they can deal with and maybe even function extremely well and Etc so maybe we could just talk about mitochondria for a moment and then talk about these two major effects what are some of the other things that mitochondria are important for uh in neurons and um and maybe other cells of the brain because as a access point for all this I think it would be great if people could learn a little mitochondrial biology yeah no it's so I guess the first thing that I'll say is that you know this field is one of the most Cutting Edge fields in medicine right now um 20 years ago or so I think the majority of research scientists thought of mitochondria as nothing more than little batteries they they take food and oxygen and turn it into ATP and that's really important yeah we get that but they're they're just little batteries that's all they are um and so one of the reasons that this work is so important is it is because it combines Cutting Edge research in the metabolic field and the Aging field and we can start to par it with the mental health and neurological health field so mitochondria you know one one scientist gave me this analogy he said if you think of the cell as a computer a lot of people think of mitochondria as the power cord to that computer because they're providing the power and they are in fact the power cord to that computer but actually their real function is the motherboard of that computer so mitochondria are directing and alloc ating resources throughout a cell that is their primary function and then they happen to be powerhouses as well and so to to give some clear examples mitochondria play a direct role in the production and release and regulation of some really key neurotransmitters including serotonin dopamine glutamate Asal choline um those are pretty powerful neurotransmitters yeah I would call those I would consider those the I know you listed more than three but uh the sort of primary colors of neurotransmission yes you know any one of those in excess or deficiency is going to have profound negative effects on a nervous system or it's going to alter the way that people and animals feel think move remember Etc and so as part so mitochondria are providing both some of the building blocks if you will for some of those molecules they're part of the kreb citric acid cycle some of the some of the intermediate products actually go into making those neurotransmitters much more importantly mitochondria provide the energy for the production of those neurotransmitters and fascinatingly mitochondria are directly related to the release of neurotransmitters ATP alone is not enough there have been some research studies that have actually found that mitochondria move along the membrane of the synapse to release batches of vesicles of neurotransmitters and that if the mitochondria are removed from the synapse and researchers flood that cell with ATP neurotransmitters usually are not getting released mitochondria are doing other things we don't entirely even understand what all they're doing or how they're doing it but they're doing other things than just providing the power another really important example is that mitochondria are actually the primary Regulators of epigenetics if you look at any one factor so one study actually found that they're responsible for the expression of about 60% of the genes in a cell and so and mitochondria do this through a lot of ways that have been known for years and sometimes decades so mitochondria are directly related to the levels of reactive oxygen species in a Cell they are managing calcium regulation in cells um and we know that those things play a role in epigenetic expression we know the levels of ATP to ADP or also play a role um and mitochondria are doing those things but it turns out mitochondria actually doing much more sophisticated things than even those in terms of gene expression mitochondria at least play a role in all of the aspects of the human stress response so um when humans are stressed either physically or psychologically uh you know there are several things that happen um increased cortisol increase adrenaline noradrenaline uh inflammation and gene expression in particular in the hippocampus occur with the stress response and one group of researchers actually genetically modified mitochondria in four different different ways and found that all of the stress response all those four buckets of stress response were impacted in one way or another implying that mitochondria are somehow playing a role in those in terms of it their role in cortisol we know that mitochondria actually have the enzyme required for the synthesis of steroid hormones so that includes cortisol estrogen testosterone and progesterone some names that maybe everybody's heard of and uh so that means that if mitochondria are in short supply or dysfunctional the production of those hormones may become disregulated um mitochondria play a direct role in inflammation and they turn the inflammatory system both on or they at least play a and turning the inflammatory system both on and off I think I'm not going to be able to quote the exact study and author but one paper in cell actually identified mitochondria as the key regulator in turning certain inflammatory cells off and that when you inhibit mitochondrial function those cells don't turn off that mitochondrial levels of reactive oxygen species are a key signaling process to turn the inflammatory C process off another study found that macras is so macrophases are an important immune cell that play a role in healing so if you cut yourself your your body will get you know send inflammation that way and uh and send immune cells that way to try to heal your skin and macroasia play an important role in that healing one group of researchers tried to figure out how do macras know to switch between the different phases of wound healing because the macrophases do different things in the different phases of wound healing and the conclusion of all of their research was that it's mitochondria mitochondria are sending the essential signals that change the state of the macroasia to induce these different phases of wound healing so so I've just talked about neurotransmitters hormones epigenetic expression inflammation and for anybody familiar with the mental health field they know these are like some of the key variables that researchers have been struggling with for decades trying to figure out how do these fit together we know that all of the those buckets can be disrupted in people with mental disorders and our field has struggled to understand but how how do they fit together how can we make sense of this disruption and I believe once you understand the science of mitochondria you can actually connect all of the dots of the mental illness puzzle I'd like to take a brief break and thank our sponsor insid tracker insid tracker is a personalized nutrition platform that analizes data from your blood and DNA to help you better understand your body and help you reach your health goals I've long been a believer in getting regular blood work done for the simple reason that many of the factors that impact your immediate and long-term Health can only be analyzed from a quality blood test the problem with a lot of blood and DNA tests out there however is that you get data back about metabolic factors lipids and hormones and so forth but you don't know what to do with those data inside tracker solves that problem and makes it very easy for you to understand what sorts of nutritional behavioral maybe even supplementation based interventions you might want to take on in order to just the numbers of those metabolic factors hormones lipids and other things that impact your immediate and long-term Health to bring those numbers into the ranges that are appropriate and indeed optimal for you if you'd like to try insid tracker you can visit insid tracker.com huberman to get $200 off an ultimate plan or 34% off the entire site as a special Black Friday deal now through the end of November again that's insid tracker.com huberman and use the code huberman at checkout super interesting little subcellular goodies these mitochondria are I I um I come from a field where people are often divided into lumpers and Splitters and um I'm somewhere in between um for those of you who don't know lumpers are people that like to make things really simple lists of no more than three functions or dividing brain areas into no more than three Splitters of people that like to subdivide into a ton of detail um there's a history of scientists being Splitters in order to be able to name things after themselves because you know there's more territory to go around if you're splitting than if you're lumping um but we are doing neither here what what I'm hearing is that mitochondria in addition to being important sources of energy production and output in cells which of course they are um probably have other roles and that maybe maybe someday what we call mitochondria will actually be two or three different little subcellar organel like there may be little bits in there are controlling gene expression and little bits in there that are controlling neurotransmitter production at least for now that the name is mitochondria and thank you by the way for um illustrating some of the other things that they do because um in the landscape of Science Education uh oftentimes people will think okay energy production there'll be a picture or a cartoon of mitochondria like flexing its muscles people go okay energy mitochondria Mighty mitochondria and then they'll think oh you know they're just sort of like a dumb jock portion of the cell right they're not doing anything sophisticated and everything you listed off is that they are doing many sophisticated intricate things within cell so I think how things are cartooned and discussed actually has an impact and not just on the general public but on the medical field and on the science Fields anyway that's more science sociology but now that um everyone is well aware that mitochondria are doing a large number of very important things in a very regulated way let's talk about mitophagy you know a few years ago because uh a Nobel Prize was given for autophagy sometimes called autophagy look people you can say it either way people know hopefully what it means is more important which is the gobbling up of One's Own cells that are dead or injured or um and this idea of autophagy of cells uh being eaten up or within a system nervous system or other system um has come up again and again I actually wasn't aware that mitophagy could be such an important lever so tell us about mitophagy which I have to presume is the um intentional or not gobbling up of mitochondria presumably to replace them with newer healthier mitochondria is that right it is so in and in many ways mitophagy is a subset of autophagy um but it is it's got its own name because it is specific to mitochondria there do appear to be some unique Regulators of mitophagy compared to autophagy more broadly mitochondria actually are playing a a role in autophagy itself um and this makes sense because one of so the global picture of autophagy is stimulated by fasting States or fasting mimicking States so when your body senses that you don't have enough food it actually hunkers down and starts to recycle dead old Parts um in this kind of carefully orchestrated way and it takes them to lomes they get degraded and then those degradation products get used for either energy or to build new things autophagy is always occurring um at a low level but you can really hyper stimulate the process through fasting calorie restriction fasting mimicking diets other things and this is why fasting and fast you know calorie restriction is so kind of such Hot Topics in the medical field now is because we they've been shown to induce longevity and we think it's probably through that process that you're you're stimulating the body to um kind of become lean and conservative in terms of its allocation of resources and the body doesn't just destroy the healthiest tissue along with the old dead stuff it has these processes that identify the old and defective Parts first and they go first and that's what's beautiful about the whole thing and that's why fasting is so important so mitophagy um we know plays a really important role because uh so there's this term called mitochondrial dysfunction which some researchers are actually wanting to get rid of and move away from because as you just said mitochondria do so many different things and different mitochondria even within the same cell may very well be specializing in different tasks and mitochondria from one cell to another are sometimes doing very different things like not all mitochondria can produce cortisol that's specific to specific cells um where those genes are getting turned on so it's not like all mitochondria are producing cortisol just the ones in your adrenal GL for instance are producing cortisol um but there is this term mitochondrial dysfunction and it has long been known for decades that mitochondrial dysfunction is associated with everything that ails us essentially so um in the 1950s we had a Theory of Aging that was based on reactive oxygen species and that essentially and that's where all the inflammation is bad for you comes from and where all the um noise about antioxidants yes like in the 90s I was like it contains antioxidants not to say antioxidants are bad but they are certainly not the be all end all of Health they are not but that's exactly where that research came from is that researchers were narrowing in on these reactive oxygen species are highly highly correlated with all of the diseases of aging and poor health outcomes turns out they're also highly highly correlated with all chronic mental disorders interestingly and so researchers used antioxidants to see if well maybe if we can stop somehow tame these reactive oxygen species will improve health outcomes doesn't seem to work by the 1970s our understanding of mitochondria and their role in the production of reactive oxygen species expanded and that to the mitochondrial Theory of Aging so in the 1970s we had this mitochondrial Theory of Aging based primarily and exclusively on reactive oxygen species fast forward a couple of decades that was disproven because we now know reactive oxygen species aren't all bad they actually serve a signaling process they're a normal part of human functioning and cellular function so they're not all bad but we still know high levels of reactive oxygen species are bad for you fast forward to just I think maybe last year with this expanded role of all of the different things mondria are doing so David Sinclair uh published a p paper in one of the cell journals I think uh saying that oh mitochondria are actually the unifying link of everything that we know about aging mitochondria are the cause or defective mitochondria or defective mitochondrial function mitochondrial dis dysfunction is possibly the unifying cause of aging and all of the Aging Related Disorders um so mitophagy is trying to address all that is trying to say okay this is bad we don't want defective mitochondria and how can we get rid of old ones or defective ones and and replace them with new ones and I think the most powerful signal and tool that we have right now is in fact related to diet it's calory restriction that is the oldest truest kind of best proven way to prevent Aging in a wide variety of animal species fasting and intermittent fasting and again you can only do those things for so long and then fasting mimicking diets um can also stimulate this process of mitophagy before we talk about mitochondrial biogenesis um if and I certainly accept the idea that mitochondria are extremely important in physical health and mental health that's for me is is a straightforward uh conclusion at this point based on what you've said what I've read elsewhere Etc and if various diets including ketogen diet including fasting reducing sugar intake Etc can assist in mitochondrial function and mitophagy and that's at least one of the levers by which diet can positively impact mental health and physical health can we conclude that there's something special about low blood glucose in the brain right I mean that the the sort of common pathway of all of those things fasting ketogenesis for some people maybe they for maybe some people managed have great insulin management so just removing sweets you know refined sugars you know brings down their blood glucose level substantially they don't need to go on a ketogenic diet in order to relieve a low-level depression or something like that seems like the the common theme Here is that glucose levels in the brain need to be reduced which for me is surprising because neurons love glucose I mean there are some really nice studies one that I can think of um recently that was publishing neuron if you just look at the tuning of a neuron how well a neuron in the brain represents some visual image in the environment in terms here we can just generalize in saying more action potentials more electrical signals from the neuron generally correlates with better High Fidelity representation it's like sort of you if everyone time someone says shout and then someone shouts the neuron is like the one responding to the the order and these neurons just when there's high glucose they are faithful representatives of what's out there in the world but then when you fast an animal they become less faithful representatives of what's out there and yet when I've done intermittent fasting and I do a kind of modified version of it my mental Clarity is far better than when I've had a big bowl of pasta probably for other reasons related to serotonin and tryptophan and so I think um for the typical listener out there after to imagine it's got to be a little confusing right we hear neurons love glucose they live on glucose and here we're saying let's deprive them of some glucose or let's just bring glucose levels down or let's switch the fuel source of the brain from glucose to ketones and now the brain really works the way it's supposed to so this raises a little bit of a just so story question like why would it be the case that neurons love glucose and yet if there's too much glucose around they become sick um and of course with any uh why would it be story as I always say you know I wasn't consulted at the design phase and I'm going to presume that you weren't consulted the design pH either and that if any of us say that we are then we are probably the patients that need evaluation so um I think there's a name for that right there's delusion right okay go my first correct clinical assessment of myself so um how do I get my head around this right you've got me sold on mitochondria not that I needed to be sold but that's an easy like yes yes absolutely yes the idea that diet can impact mental health and physical health yes absolutely by way of mitochondria at least in part great but then neurons low glucose so what's going on or what do you think is going on I am not convinced that glucose is the real story glucose May in fact be a symptom so we know that we know that parts of the brain you know there was a there been a couple of studies that just came out in the last couple of weeks I think um documenting that actually asites in the hypothalamus play a key role in glucose regulation throughout the body and uh and it appears to be a metabolic role which in my mind implies that the mitochondria in those asites are probably playing a key role because we know mitochondria play a key key role in sensing glucose levels they play a key role in the release of insulin from the pancreas but mitochondria in the brain is also playing a role in kind of balancing how much glucose is around and so it's it's a difficult question because I think in some cases high glucose levels are actually a symptom of metabolic dysfunction somewhere in the body or brain and when I think about what does that [Music] mean in my mind most of the evidence currently is pointing to mitochondrial dysfunction somewhere in the body or brain that is the most likely cause of that disregulation of glucose levels um but we know that if you consume massive amounts of junk food sugar and other things that you can get disregulation of glucose levels the the conundrum though is that that's not a universal response and what about the typical person like I've never really liked junk food that much maybe as a kid I can recall it liking candy but I was a sandwich for lunch person for a long time and as I've changed that out for salad and uh maybe a small piece of meat with my salad or something like that I feel far better during the day far more alert but I do eat carbohydrates I eat starches typically at night but I tend to do some very hard training at some point during the day so I imagine I have some glycogen to repack okay that's me I only mention that because I'm not in ketosis as far as I know I haven't unless you brought the the strips I haven't uh done the blood glucose test today um so what about the the typical person who's an omnivore eating um you know some rice some pasta pasta salads you know people that are that are eating not junk food massive amounts of sugar but have blood glucose that's in kind of moderate range do you think and here feel free to speculate do you think that those people might feel far better or even a little bit better if they were in a lower glucose State and I asked this because I think there are a lot of people out there who suffer from full-blown depression but there are also a lot of people who suffer from like moodiness and feeling Not So Great subclinical Depression yes burnout is what I would call it yeah and and just feeling like some days are great and then other days they feel lousy for reasons they don't understand yeah um and those make for Less dramatic case studies and yet I have to assume that that description will net some a large fraction of the general public so the the way that I kind of break this field and I'm probably getting too nerdy right now but I kind of break this field into cause what's the actual root cause and what are effective treatments and I really see them as two separate things simp just because the ketogenic diet is an effective treatment does not imply that the cause of the problem was eating carbohydrates and I think that's a really important distinction there are many people who disagree with me on that there's no doubt about it and everybody's heard people say sugar is the cause of everything that ails you or carbs are the cause of everything that ails you if everybody does a low carb diet or a ketogenic diet and then they go to so it must be sugar that was the cause I don't see it as clearly black and white is that the calorie restriction ketogenic diet carbohydrate restriction are inducing metabolic changes in the brain and body and regardless of what the person was eating they are inducing metabolic changes that can be really beneficial to brain health so let me let me just give a clear black and white example of this and then I and then I can speak to the broader topic that you brought up about just the general population the easy example of the ketogenic diet being an effective intervention for somebody who was not following a bad diet is an infant with epilepsy there are lots of infants who have uncontrollable seizures they are drinking breast milk to the best of our knowledge that is the primary most beneficial food source and imp could be consuming now some might say well maybe the mother's you know what whatever I I don't buy that the mother's breast milk is in fact the the the optimal food source for that infant and yet that infant is still seizing if we put that infant on a ketogenic diet a lot of those infants seizures will stop it doesn't mean that the cause of the infant seizures was a bad diet but it means a dietary intervention can change change brain metabolism and improve symptoms in that person so going to your broader question about adults modern day the real answer you know there was just this conference in London the Royal College of obesity medicine or something like that that's not the name but it's something along those lines the conclusion of that conference that invited the greatest Minds in obesity medicine the overarching conclusion of that conference was we don't know what causes obesity it's really important that we sit with that we don't know what causes obesity they don't think excess caloric intake Beyond one's daily metabolic needs is causing obesity some will argue that but and and so some will say yes it's all energy balance but why do we have an epidemic of obesity ah well that's a a that's the gazillion dollar question and and junk some will say it's all the junk food but we had junk food in the 1970s when I was growing up I grew up on Kool-Aid and twinkies and kingdong and hoos and oh I'm rewatching I'm rewatching the Mad Men series now I love that series and I'm rewatching it and I I happen to know someone who worked on that series they research everything for the prop and the costumes everything but right down to diet and if you look at the the diet it was terrible it was mostly yes there was a lot of excessive amounts of drinking and cigarette smoking but the diets were terrible it was prepackaged Foods it was frozen dinners I mean that really came to prominence in the 70s and 80s um but uh even in the 50s and uh from what I've been reading even in the 30s and 40s you know it people were not eating grass-fed meat and Brazil nuts with a little bit of broccoli RAB on the side does not the typical intake um so something something out there or maybe multiple things are at play to increase obesity and at the end of the day I believe some will call this speculative but I actually think we've got a tremendous amount of evidence that continues to point in this direction I believe that mitochondria are the key to the Obesity epidemic that there is something in our environment so that is either our food environmental toxins stress levels poor sleep not getting adequate sunlight whatever you want to speculate on all all of the above all of those things are known to impair mitochondrial function and if if if parts of your brain that regulate metabolism and that regulate eating behaviors are not metabolically healthy it means that they will not stop you from eating or it means that your metabolism will not rise to the challenge of 10 Donuts um because some people can eat 10 donuts and go on staying thin and healthy although I I totally agree although I would um just like to say that it seems to me that compared to when I was growing up and again I haven't run the statistics there are fewer and fewer of those individuals around now now just as when I was growing up it was one or two kids in class that were quite overweight and then there were some that were mildly overweight but most were of healthy weight nowadays that's dramatically altered the landscape is dramatically altered in the other direction um it is rare when I encounter one of those can eat anything type people I know one he's actually an employee at Stanford he's on our media team at Stanford and and this guy I when I take him to lunch it's like the am he's in his uh early 70s and he can eat and he's incredibly lean he exercises a little bit but he's one of these mutants that just can eat and eat and eat and he's lean and he's vital and he's it's it's wild um and he's an expensive lunch um uh but those people are seem rare and even those kids are now seem rare they're getting increasingly rare and and that that leads me to think it may be epigenetic fact factors in the womb environment so that kids are actually coming out predisposed to obesity well let me ask you about that because I had a note here to ask this later but I'm going to interrupt you now in order to capture this moment my understanding is that well as everyone knows we inherit DNA we get genes from both of our parents and they mix although there are incredible data from Katherine Duck's Lab at Harvard and others showing that we actually have entire regions of our brain that carry uh neurons that are of purely of mom's or of Dad's DNA depending on the brain region this is a wild finding and um but it's accurate and this has actually been known about in in terms of heritability of disease Etc maternal DNA DNA from Mom genes from our mother not to place blame on Mothers at all my understanding is that the mitochondrial DNA come exclusively through the maternal side is that true so it's a great question and I've been asked this before and yeah psychiatrists are known for blaming mothers and some might say that I'm like trying to redo that whole thing and blame mothers again the you know the data or the data I'm not trying to blame mothers here mothers play an essential role um in in everything um but if if it is true that mitochondria are the Lynch pin of all this and maternal DNA is what determines the mitochondrial DNA I think it's an important place to look it's an important question and the answer is unequivocally no that's not the way it works oh well then so Vindication for anyone that was asserting that and so let me explain it so mitochondria have 36 genes unto themselves 13 of those genes code for some of the mitochondrial Machinery of making ATP and the other 36 play roles in um epigenetic regulation play roles in whole body metabolism and other things but so that is what you're inheriting from your mom is the mitochondria and those 36 genes for the most part part but the majority of proteins that make up mitochondria over I think 1300 genes that make up mitochondria are actually encoded in the nuclear DNA and so you inherit a copy from both your mother and your father so the majority of people who have mitochondrial defects or M rare mitochondrial diseases actually could inherit them from either mom or dad because it can be a defect in um the nuclear genes that code for proteins that make up mitochondria the much bigger issue when so when I talk about mitochondrial dysfunction being a primary driver of mental illness metabolic illness it's not that people inherit a defective mitochondrian or mitochondria from Mom and then that just ruins their life forever that's actually not the way it works the beautiful thing about this theory is that it connects all of the risk factors that we already know play a role in mental health but also metabolic Health Sleep disruption impairs mitochondria and mitochondrial function stress high levels of stress and Trauma impair mitochondrial function drug and alcohol use Alcohol tobac Tobacco definitely in terms of the smoke and uh marijuana THC in particular all impair mitochondrial function THC directly or or the the smoke um THC directly those Studies have been done and they so mitochondria actually have CB1 receptors right on them and uh and various researchers a couple of studies from nature actually documented this that that the mitochondrial CB1 receptors are primary um uh kind of primary points of the influence of marijuana on human behaviors and effects so um because when they remove CB1 receptors and animal models these changes don't happen so the CB1 receptors um you know we've got some large studies of adolescents who used a lot of marijuana and the areas where the mitochondria have the greatest number of CB1 receptors are areas of their brains that actually are atrophied or shrunk compared to normal healthy controls so that means their brain tissue is aging prematurely it's shrinking prematurely um but the CB1 receptors on mitochondria also seem to play a role in the memory impairment that can be induced from M from uh THC and they also play a role in uh the kind of lack of motivation the behavioral a motivational State uh from THC now again for people who want to chillax that's what they're looking for they don't want to remember anything they they don't want to think they they they want to be spaced out they want to relax that's great um but it's important that they know that they're actually harming the mitochondria in their brain cells and that although there's always an opportunity to repair mitochondria and always an opportunity to stimulate mitochondrial biogenesis so you can get it back but if you keep doing it chronically you're probably not helping your overall mental or metabolic Health yeah I'm glad you brought up THC we did an episode on canas we also did one on alcohol probably lost some friends uh from that one I mean when you look at the data it's very clear I mean I'm not arguing that people dislike the effects of these compounds when they take them um but it is clear that at least to me based on the data that regardless of what people have read about red wine that not drinking any alcohol is going to be healthier than drinking alcohol and that the thresholds for alcohol ingestion before people start to negatively impact their health is about one or two per week and then THC because of the very high concentrations of THC that are present in a lot of products now vaping and smoking THC and even Edibles that it it can be problematic you mentioned adolescence that you know predisposition of brain atrophy psychosis Etc in any case um because you mentioned alcohol and because it is a commonly used um substance uh I heard you give a talk in which I think I have this right in which um alcohol can disrupt the way that the brain uses fuels of all kinds which May disrupt one's response to alcohol make alcohol seem um more uh uh rewarding to those that drink alcohol so drinking alcohol makes alcohol more rewarding to the brains alcohol yes drinkers um but that it also might alter glucose metabolism that basically alcohol is not good for our brains um it do I have that correct you do have that correct okay um what happens if you take alcoholic or somebody that just drinks you know two to four nights a week a couple of drinks which I think is pretty common out there um and you put them on a ketogenic diet has that experiment been done that experiment has been done and uh by uh led by none other than a woman named Nora vula who is one of the leading neuroscientists um and addiction researchers in the world she is the director of the National Institute of drug abuse she's been hot on the trail of metabolic abnormalities in the brains of people with alcohol use disorder which I will just refer to as alcoholics because that's what everybody knows it as um so she's been hot on this Trail for many many years and uh and as you said it turns out that um the reward Pathways in particular are metabolically compromised in Alcoholics and the metabolic compromise essentially in a nutshell means they aren't getting enough fuel from glucose the interesting thing is that when people drink alcohol your liver converts alcohol into a molecule called acetate that acetate travels up to the brain and fuels brain cells in particular some of these reward pathway cells more than others and uh so chronic alcoholics have this chronic deprivation of energy in these cells and so norov vola and other researchers thatal Institutes of Health uh did a study in which they they set out to see if we can change this brain metabolic problem in Alcoholics will that affect clinical symptoms of alcoholism and will it do anything you know it's clinically useful and so they actually did a pilot randomized controlled trial admitted alcoholics to a detox unit half of the patients got a ketogenic diet the other half got the standard American diet then everybody else all of them got the same detox protocol the patients who got the ketogenic diet required fewer benzo aines for their detox despite that they had fewer withdrawal symptoms from the alcohol they reported fewer cravings for alcohol and the researchers did brain scans which showed improved brain metabolism in these key areas that they were looking at and their brains showed reduced levels of neuroinflammation which was also something they were really interested in and so that one study says to us that even though most people would think alcoholism has nothing to do with Diet alcohol is just drinking too much it's a matter of willpower or it's somebody who's addictive you know they've got an addictive personality and it's it's that simple you come out of the womb with an addictive personality and those people are you know novelty Seekers and they're impulsive and they have no patience they have no discipline they can't sustain you know any kind of rewarding experience or childhood trauma there's a de there's a yes story there which there very well may be but and there may be yeah and but what that research study strongly suggests and again yes maybe we need larger controlled trials but this is one of the leading neuroscientists in the world who's hot on this Trail this is what she believes and this is what I believe is that if we can correct the brain metabolic defects from chronic alcohol use we might be able to help people be sober um and give them a fighting chance or give them an edge up or pull a lever that we can use in their favor for their benefit there's one caution to all of this research that I really do want to highlight and so now I'm you I'm going to get hate mail from all the keto Community um that's okay I mean anytime I admire you for talking about nutrition at all because anytime uh one talks about nutrition you're going to get hate mail from somebody but um so the the caveat to all of this is that as part of the research that those um researchers were doing they actually wanted to see what will happen to alcohol levels if an animal consumes alcohol while on a ketogenic diet so they didn't do this in humans yet this is a fairly easy study to do so I'm hoping somebody will do this study soon but they they instead put rats half of them on a standard diet and half of them on a ketogenic diet and then they expose them to the exact same amount of alcohol the rats who were on the ketogenic diet had a fivefold increase in blood alcohol levels fivefold increase meaning they drank more or it was metabolized differently it was metabolized differently they the rats all got the same amount of alcohol so for um people out there who are ketogenic I'm chuckling but who are not alcoholics please alcoholics please do something about it because it's so detrimental but um I guess does this mean that they can drink less in order to get the eff of alcohol that people are seeking cheap dates cheap date is what you call that uh you only need a half a drink instead of three drinks I would think the keto Community would thank you for this unless they somehow have a stake in the uh the alcohol industry the the reason that I the reason that I put it as a caution is that if anybody is struggling with alcoholism and thinks hey I need an edge up I need a lever to pull because I'm really struggling to give this stuff up I just find myself going back and if you're telling me my brain metabolism is mess up and this might help it I'm all in favor of that and yes that's what the researchers are pursuing and that's what I'm saying with the following caveat that if you relapse while on a ketogenic diet you better not drink the same amount of alcohol that you think you can drink um could be deadly it it could be deadly and Andor it could be really yeah deadly to you or someone else because unfortunately a lot of times when people drink they get behind the wheel and they think that they can handle two drinks safely and they they think well you know I can go out for dinner and have two glasses of wine and drive home safely I know myself if you go to a ketogenic diet please don't drive with the same two drinks because it means your blood alcohol level if it's any if it models anything that we found in the rat study your blood alcohol levels may be five times higher than they would normally be and that means you are really wasted uh and you're probably not safe to be driving probably the same is true for drinking on an empty stomach right yeah yeah no it's a very important point and than thank you for raising that I mean I hear this uh again about mitochondria about blood glucose I you mentioned asites and for those of you um heard that earlier asites are a non-neuron cell type in the brain a gal cell type that um my post advisor are was um known for sort popularizing the modern science of of glea which include asites and I'd be remiss if I didn't say that they do they are considered the the cells that hold everything together in the brain and are kind of passive observers but they do many things actively they're they I think now people appreciate the asites as at least as important as the neurons um and certainly for disease they are often implicated in um warding off of disease Etc everything that you're telling me about the fact that the brain can regulate things that are happening in the body metabolism Etc organ health obesity Etc to me as a neuroscientist that's not surprising all of it just screams hypothalamus hypothalamus hypothalamus because here you're telling me it's regulating these basil functions like metabolism it's regulating how much We crave things and of course hypothalamus is involved in motivation and craving there are other areas too other areas of the brain too of course but I would imagine that someone ought to or has mapped out where the you know the receptors for all this business are in the brain and and um you know and I guess that raises the question of when one goes on a ketogenic or low blood glucose diet or fast has anyone observed changes in the brain has anyone done neuroimaging of humans and their brains uh under conditions of ingesting one diet or another whether or not they're psychiatric suffering from a psychiatric order or not I would think that I would think that's where the the gold is we do have some of those studies so and they've the you know when you do a neuroimaging study you can measure a lot of different things so one thing with a pet scan you can measure glucose metabolism so a a researcher Steven Kain is doing that research in particular in Alzheimer's disease patients um and Alzheimer's disease models but in humans um and that's because we know that um again a a a common finding in patients with Alzheimer's disease is this glucose hypom metabolism some people are attributing it to insulin signaling impairment and so some people are calling it type 3 diabetes at the end of the day I think the clearest um signal that we have is that cells aren't getting enough energy from glucose as a fuel source that is something that I think I can confidently say that's backed by numerous research studies there's debate in the research field about whether that's Prim a primary driver of the illness I happen to believe it is and I if you ask the question well why would cells not be getting enough fuel from glucose you have to focus on mitochondria because they're the ones producing the fuel from that glucose so you somehow you have to implicate mitochondria in that process one way or another um others will say no that's just you know a side effect of whatever is causing Alzheimer's disease but so Steven gain has done studies where he even gives Ketone supplements these are liquid Ketone Esters so yeah Ketone Esters or Ketone salts and it has actually found that these brain metabolism deficits can be corrected at least short term by giving a ketone supplement is this um in the context of people also ingesting some carbohydrate because I I confess I I've tried the ketogenic diet I probably did it wrong this was years ago and then the cyclic ketogenic diet but in the last year or so I've started using liquid Ketone Esters but I and I do eat some carbohydrates each day usually in proportion to how much high-intensity exercise I'm doing those liquid Ketone Esters for me at least subjectively I feel like greatly increase my energy levels and my ability to focus mentally and improve my sleep this is my observation tracking some data but just again subjectively so in this example are you talking about people taking Ketone Esters or Ketone salts on a backdrop of a ketogenic diet or on the backdrop of a more typical diet so he's done both so he's done um he's done studies where patients aren't doing anything special with the diet so they're eating whatever they normally eat absolutely non- ketogenic giving them a ketone salt or Esther and then noticing immediate and direct changes in the metabolism of these metabolically compromised brain cells by as measured by PET Imaging um these are not household pets by the way I'm sorry I you have to just pach your positron emission tomography not pets although I'm sure that there are people out there who have their dogs or cats or whatever or their you know pet kangaroos whatever you might own on ketogenic diets okay not absolutely right so he's actually moved further he's done a pilot trial in a nursing home actually where he did not put the patients on a ketogenic diet he simply reduced carbohydrate consumption at breakfast and lunch they still got the same dinner as everyone else and simply reducing carbohydrate consumption at breakfast and lunch resulted in cognitive Improvement in in a statistically significant way in some of those subjects I love that result I'm sorry I just have to highlight this I'm a huge believer in in directing carbohydrates to specific portions of the day when one needs to be less focused and alert and yet can replenish glycogen um limiting carbohydrates most of the time during the day for me has been a game Cher in terms of maintaining alertness Etc I'm not aware that I have you know age related cognitive decline but then again I would people around me May argue let me say you are Andrew huberman there is no way you have cognitive impairment although you didn't know me as aye old have cognitive impairment we're all screwed well I have plenty of flaws and impairments I'm well over 3,000 documented by people very close to me so um but this is very interesting I I think in the context of everything we've been talking about because could it be that supplementing with liquid ketones or prescribing liquid ketones to people who are challenged with um mood disorders or things of that sort could be beneficial even if they are not willing or able to adhere to a ketogenic diet that is the million-dollar question right now and we don't have good trial data to say yes or no my speculation my my hunch having tried that clinically with patients is it doesn't seem to work it's not the same thing my the bigger reason for my feeling confident in saying that is that we've had Ketone salts and Esters available for over a decade now we have tens of thousands of children and adolescen who are following a strict ridiculously strict ketogenic diet to control their epilepsy those kids would love to be off the ketogenic diet their parents would love to have them off the K birthday cake no ice cream there is not one case report of any child controlling his or her seizures using exogenous ketones without also doing the ketogenic diet I just find it hard to believe that at least some of those people haven't tried it out to see I do know some patients with bipolar disorder and even schizophrenia who are doing extraordinarily well on a ketogenic diet they have tried to switch off the ketogenic diet using exogenous ketones their symptoms came back and so they they found that it just wasn't effective again those are anecdotes my scientific speculation about why is is because the ketogenic diet is actually not necessarily about ketone themselves ketones are one of a multifaceted story there and so when people do a ketogenic diet they're also improving they're lowering glucose levels they're improving insulin signaling they're ramping up mitochondrial biogenesis in particular in the liver because mitochondria actually make ketones that's where they're made and they're primarily made in the liver mitochondria so when somebody's on in a fasting state or on a ketogenic diet their liver mitochondria go through the roof because they're being called to action it's like hey body's in Starvation mode get to work and so the mitochondria you the the cell senses we need more mitochondria to process fat to turn it into ketones so that those ketones can get up to the brain and keep the brain fueled because fatty acids can't fu fuel the brain only ketones can now so my sense is that and the gut microbiome changes and everything the changes in hormones so if you're eating a lot of donuts and drinking a bottle of ketones the donuts are going to prevent your body from lowering glucose levels you're still going to have the high glucose levels from the donuts you're still going to probably have the impaired insulin signaling you're probably still going to possibly have some inflammation from the inflammatory effects of that food um and and so just drinking ketones alone won't be enough I think I think for people who are metabolically healthy I'll include you in that I think ketones can play a really beneficial role no doubt I think exogenous ketones May in fact prove invaluable in clinical use for patients who maybe can't follow a super strict ketogenic diet but maybe could do a low carb diet and then given the research that's happening with alcohol use disorder I could imagine a situation here's the million dooll like you know uh tip to whoever wants to go out and get this if it actually turns out to be true I could imagine a scenario where we use exogenous ketones with alcoholics and that every time they have a severe craving for Al alcohol they drink ketones instead which sort of tastes like alcohol the the Ketone Esters I when I take them they I drink them straight sometimes I put them in Seltzer and I'm not a big drinker as I mentioned I might have an alcoholic drink every once in a while um I just don't ever crave it I just do it every maybe think I think 2020 was the last time I had a drink of alcohol um so obviously I'm not a good representative example um but the ketones taste good to me and they obviously don't get you drunk they just they do seem to um flick on my alertness pretty quickly the and I my understanding is that they are the brain's preferred fuel source meaning they are going to be the first fuels used by the brain in when there's a buffet of of fuels available if there's glucose in my bloodstream there's circulating liquid ketones that ketones would be used first or preferentially is that true I think it's a complex question I mean some some research that we have suggest that there are brain areas or brain cells that require glucose and cannot use ketones so 100% of the brain cannot be fueled with ketones as far as we can tell so there are some areas that require glucose and that's probably the reason we have gluconeogenesis is to keep the body going and keep the the brain going no matter what um but when ketones are available especially if ketones are High um the way I think about it is not that ketones are like the preferred fuel source and glucose goes to the Wayside but the way I think about it is that you have a range of cells with varying degrees of metabolic health and some of those cells are going to be extraordinarily healthy with appropriate healthy abundant mitochondria and those cells are probably going to continue to use glucose as a fuel source but if ketones happen to be there sure they'll use that too like why not but the real money is metabolically compromised tissues um whether it's brain cells or other tissues that but we're talking about the brain so if you've got metabolically compromised brain cells because it's not across the board like with Alzheimer's brain scans there are specific regions that are more metabolically compromised than others and that's why we see patterns of atrophy in specific brain regions is because those regions are dysfunctional metabolically for whatever reason and you know you we can get into why that might be but but my sense is that if you've got a metabolically compromised cell that cell is sending out a distress signal that cell is calling resources from the body like feed me give me something and if it can't use glucose effectively it is going to suck up those ketones and then start running on all cylinders or closer to it and and that that process is so critical because what it means is that if that if that cell was barely getting by on 60% of its real ATP requirement it means that it doesn't have enough energy for maintenance and repair functions as soon as you give that cell 100% energy or close to it um even if you get it up to 90% of its you know preferred energy amount um it can start to repair itself I mean that's the beauty of the human body and living organisms is that they have a priority list of of what they're going to do and and if they if that cell senses that there are defective molecules defective proteins in this cell that need to be replaced um once it gets enough fuel it will start repairing itself and doing that work that makes sense thank you for that clarification um I'd like to talk about Alzheimer's and age related cognitive decline generally uh I know many people out there are just terrified of losing their memory for the obvious reasons memory sets context Etc and many people have relatives that suffer from Alzheimer's or other forms of dementia I've heard that the ketogenic diet and diets like it can be very effective for helping to offset some of the symptoms of Alzheimer's and age related cognitive decline in fact I even have a a friend I won't out him by institution who's the chair of Cardiology who contacted me of all people um asking whether or not I was aware of any studies or whether or not I knew of anybody who had benefited from ketogenic diet for Alzheimer's and I thought why don't you ask one of your colleagues in neurology but his response was really interesting he said there's there are many books out there for the general public there are a lot of online discussions about this there are a lot of assertions about this and some animal studies but the again these are his words there are very few if any controlled clinical trials exploring the role of the ketogenic diet for the treatment or reversal of Alzheimer's and AG relay cognitive decline I'm hoping that statement was incorrect or soon will be incorrect because those trials are ongoing but he said yeah you know the the people are most popular for um telling us about the important role and positive role of of being in ketosis for Alzheimer's for some reason they just won't do a clinical trial and that's been frustrating to the community so this is a very educated very accomplished person who's a physician of heart medicine as opposed to something something else um related to the brain but what is the story there and um and for goodness sake why aren't there clinical trials on ketogenic diet and Alzheimer's I I don't expect you to have the to be responsible for that um fact but goodness I I would think this would be like the obvious thing for NIH I'm on study section you know but not for these sorts of experiments why isn't money just avalanching into this area based on all the anecdotal evidence that people are talking about so we've got a couple of small pilot clinical trials um the best one was a randomized controlled trial I think it only included 26 subjects something like that um randomized to 12 weeks of a low fat diet 10 we wash out 12 weeks of ketogenic diet some of the participants got keto first and then lowfat other participants got lowfat than keto and that trial actually found that when patients were in ketosis they had statistically significant Improvement in activities of daily living and quality of life and they did have Improvement in cognitive function but it didn't reach statistical significance that Improvement did not um we've got other trials we've got several animal models showing that the ketogenic diet can improve biomarkers of Alzheimer's disease in Alzheimer's models so it can reduce plaques and Tangles can even improve cognitive impairment in animal models we've got um and we've got a couple of other small pilot Trials of ketogenic diet in humans showing that it improves biomarkers compared to say the lowfat diet or the American Heart Association diet so we've got those I think one of the biggest challenges that I'll just share openly you know and this is I'm somebody who's pretty passionate about this research and I believe it has a lot of potential um but you know John's Hopkins researchers attempted to do exactly this kind of a study uh Alzheimer's patients ketogenic diet versus the I think America American Academy of Aging or something like that diet as the controll diet which presumably has starches in there I think that's the key variable probably lots of yeah lots ofes lots of whole grain some potatoes um and they spent I believe over three years they screened over 1300 partici 1300 people who expressed interest the end of the day I think they only got 27 people to enroll and only 14 of those people completed the study wow despite that what they found was that the objects who achieved ketosis had cognitive Improvement but people on study section are going to look at a study like that and say even if the science is there if you can't get people to do this diet why would we spend money on researchers trying to get people to do this diet I should mention study section is this uh closed uh door panels of 40 or so people they there are many of these panels um different uh uh different divisions of the National Institutes of Health use different panels and then grants are evaluated in in a very small um because of the size of the federal budget for research a very small um percentage usually about 10% of these studies are funded the rest um don't generally don't end up happening um that is very informative um what you just described as very very informative because um now it makes sense to me that there's no conspiracy it's not like big Pharma I don't think is trying to suppress Trials of of ketogenic um diets on Alzheimer's because I would imagine the first thing that farmer would want to do is to see that study done so they didn't have to and then the moment they would it was done if it showed a positive effect they'd probably want to isolate the molecule and wrap it up in something that people would take right yes so I don't think there's any active suppression by Pharma I think Pharma would probably be cheering from the sidelines because they could capitalize on it because ultimately the studies are done by scientists but the treatments are generally doled out by pharmaceutical companies or and or Physicians so I don't believe there's a conspiracy there that is very interesting and it's kind of amazing given our discussion of earlier which is that you had a patient that was having schizophrenic symptoms who managed to stay on this diet so is there something special about Alzheimer's patients and people with age related cognitive decline presumably they're very dependent on others to to cook for them and shop for them I think that this is a almost perfect controlled environment for getting this study done I think that is the key issue so again I got patients I get patients with bipolar disorder schizophrenia extraordinarily impaired people to do this diet and stay with it but it's because I'm providing like a weekly session for them and uh and I imagine this study did not provide that kind of intensive support so I think you know in the pilot trial that I described to you they actually got I think over 90% compliance with the different dietary interventions so some of it is going to be dependent on the research group and does the research group understand that this is not you it's not like prescribing a pill here take this pill and take it every day and come back in 3 weeks um and even then we don't know for sure that the patient took the pill every day uh we just assume they took the pill every day and studies say they probably didn't but so I think when we think about a dietary intervention we need to think about more intensive support and education and that support could be a health and wellness coach it could be a dietician it could be education of the family it might even be providing them with dietary like meals um that maybe for six months we actually provide them with ketogenic meals um once a week put them in your freezer you know microwave them when needed to make this diet as easy and doable as possible because if we can get people to do the diet if we can get them through the first couple of months most people can learn how to do this diet more importantly I didn't mention this before but the number one reason I am so successful at getting patients to stay on this diet for years is because of the consequences to them when they go off of it that is the reason I can get schizophrenic patients and bipolar patients to do this diet whereas other people can't get an everyday human being to do it for weight loss because the weight loss patient doesn't experience devastating tormenting symptoms when they break the diet oftentimes they're rewarded they they eat something they really enjoy and they get a little bit of a dopamine Rush from it and they they're Off to the Races they're like I'm going to oh I've already cheated I'll cheat again I'll get back on it someday and they never get around to it my patients when they go off the diet they start hallucinating with 48 or 24 48 hours and they quickly realized that was a really stupid thing to do that piece of cake was not at all worth the torment that I'm experiencing now so they get back on the diet I suspect with Alzheimer's disease we might notice something similar these people some of these people have very mild symptoms so maybe they won't have that kind of a reinforcement negative reinforc kind of experience but I think some of them will some of them recognize that they are impaired cognitively and if this diet could help them remember better if this diet could help them function better and again that's what the pilot trial showed is activities of daily living that means these people are able to go to the bathroom on their own they're able to get themselves dressed whereas they needed help with those things before those are actually really important things to both the patient and the caregiver and um and if they go off the diet and then quickly revert into a more symptomatic state that might be reinforcing enough for them to figure out a way to do the diet on their own and if we think about you know if this really is an effective intervention and yes we need longer trials larger trials all of that cuz there are there are plenty of stories and the medical field where Pilot trials looked really spectacular and promising and then larger trials just failed to show the benefits I believe based on all the science of metabolism mitochondria glucose hypometabolism all of that I believe the science makes this an obvious treatment that has real potential so you know people will call me bias that's fine I've got my bias no based on clinical observation and extensive clinical observation at that I think biases that are simply because uh we want to feel a certain way or believe something are are worth uh are worth critiquing but um bias based on observation here I should mention that you know most of what we know about human memory was sparked by one patient the famous hm who I think was in living in Harvard Medical uh in one of the hospitals around there many hospitals on Longwood campus but um one patient I mean the reason we associate the hippocampus with memory is because we knew that hm's hippocampus was damaged intentionally damaged for epilepsy treatment right so this idea that everything has to be a randomized clinical trial to me is crazy I mean of course that's a gold standard and it's essential but there's so much information in textbooks medical textbooks in particular that are gleaned from single patient case studies or from three patient uh neuros stimulation in the brain or something of that sort so to me I I'm still perplexed as to um you know why the why there's this um insistence on only one form of evidence um oh clearly what you're doing uh the important work that you're doing clinically and in the research side and and in public communication is is assisting this I have a question about or more of a statement SL question about the ketogenic diet based on everything that we've talked about seems to me that the ketogenic diet for weight loss is a very interesting aspect of the diet as is intermittent fasting for weight loss even though it might just be by way of caloric restriction that occurs with fasting but then in some ways the the effects of the ketogenic diet on weight loss are a bit of a Decoy for most people that's where their mind goes this person lost x amount of weight maybe that made them feel better maybe that actually made them under weight I think you've talked about it for some people it can actually bring them underweight but I'm glad that we got the chance to dive into the description of ketogenic diet for epilepsy because it really is a medical intervention that has a side effect of weight loss or could be used to treat obesity and induce weight loss but it's really about far more than that and that raises a question for me which is you know we've been talking about the ketogenic diet as one thing but I've heard you discuss this before where you know just as a physician will prescribe different dose dosage ranges of a given drug you can prescribe different dosage ranges of a nutritional plant a diet it's not one thing it's not necessarily zero carbohydrates or 100 grams or 50 grams it depends on the patient and a lot of other factors I've heard you list off various things classic keto maybe you could just briefly tell us what that typically is because I think most people think eatting it means eating a lot of meat and not carbohydrates but might not be that fasting and then some of the other you mentioned Atkins earlier we don't have to go into each of these in detail and I know in your book you talk about not just the science and clinical background but also some actionable steps that people could consider so they can refer there uh for more detail but for somebody who let's say is depressed they they've had some rounds of depression maybe they're on anti-depressants maybe not and they want to try something like this obviously this has to be done in concert with a a physician observing all this but what is the typical thing that you probe with first just like with a drug you might probe with 20 milligrams of a drug what's your typical Pro initial dietary intervention probe terrible languaging I realize and I'm I'm I'm I'm criticizing myself for that but I think people get the idea the the real answer is that I I don't have a one siiz fits-all recommendation for any person so the first thing that I'm going to assess with the patient is what symptoms are they having what is their current diet like and what are they willing to do I I try to meet them where they're at so um uh if somebody you know and I want to point out like you mentioned the all meat version of this diet which is often referred to as the carnivore diet very controversial diet there is no doubt that exists and for some people some people swear about it they swear that they've tried other versions of ketogenic diets and only when they went to a carnivore diet did they get benefits but there are vegetarian and vegan versions of the ketogenic diet so in my mind this is not at all about the diet Wars of animal sourced versus plant sourced Foods it's about inducing a state of ketosis which is mimicking the fasting state that is what it's about and you can do that by not eating anything by fasting and or intermittent fasting and you get your result so no diet is KET to is a ketogenic diet so it's not about the foods or the types of foods that you're eating it's about inducing a state of ketosis the first variable I'm going to look at when I recommend this or prescribe this is the person's current weight if if somebody's obese or versus somebody who's thin I'm going to use different dietary strategies for those two situations in the obese patient they have tons of fat stores on their body already usually it is a goal of theirs to tap into some of those and they'd like to lose some weight if they're going to try a ketogenic diet for brain health anyway and so I'm going to use that so that person really the diet is carbohydrate restriction and that usually is a sufficient intervention both simple carbohydrates meaning sugars and fructose also fructose definitely so no added sugars essentially um you can have added natural sweeteners like stevia or monk fruit you might use artificial sweeteners I'd probably years after of doing this I'd probably recommend steer away from them if you can because I think they tend to stimulate cravings for high carb foods um so if you can kind of get through a couple of weeks without um sweet things your cravings for those will go down and it'll make the diet easier and a little more sustainable but let's say you can have your artificial sweeteners if that's what really want um so I'm going to say less than 20 grams of carbs a day for those people they can have all the protein they want they can have vegetables and they can have all the fat they want but I'm not going to push fat on those people I'm not going to tell them eat a lot of fat at the same time because I want to use the fat on their body as the fat Source at least early on are you encouraging healthy fats like monounsaturated fats like olive oil or are you um encouraging people to um eat a little less butter uh Etc I I I tend to I tend to encourage again a wide range of fats and it's going to depend on the person a lot of times people come to me with very specific ideas but I'm going to tend to encourage olive oil avocados nuts which are usually considered even by the American Heart Association healthy sources of fat the more controversial thing are things like coconut oil or coconut cream which the American Heart Association might say is not a healthy fat I kind of disagree with that and don't think it's unhealthy at all actually and when you look at the epidemiological studies of saturated fat causing heart disease or causing adverse outcomes at best maybe increases your risk 10 to 15% at best how much coconut oil can people ingest anyway before they um either develop diarrhea no joke or or just sort of get tired of coconut oil but anyway um your point is taken uh but they can eat meat if they like meat or they could eat eggs or if they don't like meat and eggs they could eat sardines or things of that sort I mean I personally can't yeah I can't even stomach the I don't even like the word sardine I have nothing against the actual fish but um that's just me but obviously people have I say this because people have different preferences right yes I'll eat a steak but I'm not going to eat a sardine and I'm going to go with that and again there sources of protein that people can eat Tempe and you know other things so um that's the obese person is carb restriction is the primary initial phase the thin person is going to need to eat a lot of fat because they don't have a lot of fat stores on their body and if I want them in ketosis clinical ketosis I'm going to have to feed them fat so that's the person that I'm going to say make sure you get in avocados olive oil butter maybe cream heavy cream so heavy cream is delicious it's a delicious way to get your fats in and uh have one patient who just drinks it straight to just try to get it in other people I get it I like I've never had an appetite for sweets I um I absolutely love Savory fatty food and I when I was in high school I was I was thin so I was able to do this but I I used to drink half and half um sometimes I wake up in the middle of the night and drink it just cuz it tastes so so good it does taste good so so if they're on a ketogenic diet I'm going to push them away from half and half and toward heavy whipping cream and uh and so you can whip that up you can freeze it it turns into ice cream you can add vanilla you can add cocoa powder you can add all sorts of things and you you're off to the races with shakes and ice cream and mousse and all sorts of things that you can have um with any of these patients the beauty of this diet is I have objective biomarkers I'm going to have them measuring ketones and I'm going to adjust the diet based on their state of ketosis Andor the clinical benefits that I'm looking for if it's an average person who is not currently under psychiatric care not taking prescription medicines but is saying I'm burned out I'm exhausted I want some of that brain energy that Andrew huberman's talking about I I he he talks about feeling good I want some of that I'm probably actually going to recommend the protocol you describe which is let's see if we can just carb restrict for a while um and see if that produces clinical benefit I have one he's not even a patient just a somebody who read my book I didn't tell him anything and he came away from it saying he was ready to start an anti-press or an anti-depressant for his anxiety had chronic anxiety was trying meditation was trying all sorts of things nothing nothing those things weren't enough he was ready to go on prescription medicine he read an early copy of the book he took it upon himself without consulting with me to restrict carbohydrates alone he did not go ketogenic he is a vegetarian he restricted carbs within three 3 weeks said I don't need prescription medicine I can't believe how much better I feel and all I did was cut out some of the high carb foods in my diet so I think for some people it can be that simple for people with serious mental disorders if they are chronically depressed if they're on lots of prescription meds if they're disabled by their symptoms and certainly if you're bipolar or have schizophrenia or something those are the people I really do want them to work with a medical professional because meds may need to be adust adusted they really need a they need a real shot at this diet it's it's not like weight loss weight loss everybody Wings it and either you're successful or you aren't you look on the internet or you read a book or you do you know even the colleague that you mentioned he's probably just reading who knows whether it's credible information or not um and just winging it and seeing whether it works or not for people with serious mental disorders I want you to treat it like you have epilepsy I because you do have a serious brain disorder like it's impairing your ability to function in the world it's impairing your health and happiness you deserve a competent medical treatment and we have that we have a 100-year evidence base we've got dietitians who know this like the back of their hand they can monitor your level of ketosis they can help they can help look for vitamin and nutrient deficiencies that can be a consequence of the diet and make sure that you're not developing those they can help tweak the diet if needed they can give you ideas if you're getting bored with eggs every morning they can give you ideas for what else you might have and you know if you're using it to treat a serious disorder I think you need serious help couple of um question questions a little more detailed but um I think a lot of people will have this on their mind is it ever the case that uh you'll prescribe somebody the ketogenic diet in conjunction with intermittent fasting so eat keto but eat between the hours of whatever 11:00 a.m. and 800m or something like that that's the first question absolutely so uh and I have one patient with type two diabetes and chronic depression and he will try to follow the ketogenic diet and sometimes his blood sugars are still very high and sometimes I will ask him to do either intermittent fasting or even a three or 4 day water fast and it is shocking when he does a three or 4 day water fast you know the first day or two he feels like crap I'll just stay up front don't do it if you got an important meeting or business trip or any like don't be so this is just consuming water this is just consuming water no black coffee um um I usually tell him he can have plain black coffee or tea um but uh you have mercy after all I I have a tiny ounce of Mer Mercy but um but when he does it his blood sugars plummet in a good way like his blood sugars are normalizing but the last time he did it he actually got to seven days at one point and he said I feel great I want to keep going I can't believe that I'm not hungry but I am not hungry at all I don't miss food at all and at seven days I kind of cut the core I like no no we're done we're done you got to eat well I find it really interesting that the intermittent fasting of course controversial um at some level but um as to whether or not it's just beneficial by way of caloric restriction because it is one way to achieve caloric restriction whether or not has additional benefits but um I'm very interested in the neural side of it and it does seem that the fasted State can start to take on its own rewarding properties where people get dopamine release not from eating as most everyone does but from abstaining from food now this can be pathologic in in the sort of example of anorexia nervosa which is we both know is the most deadly psychiatric illness um but for non- anorexics I I think it's interesting to note that eventually not eating can have its own rewarding properties to it that aren't just related to weight loss but in the short term feeling in other words feeling really good by way of abstaining from eating yes yeah well and that's actually it it raises an important risk that I haven't mentioned yet but at least in psychiatric patients but even in some patients who just use the keto diet for weight loss I have seen definite hypomania so low so these are people that aren't sleeping very much they're um are they also getting kind of delusional thinking they're going to run for president no so so the the distinction between hypomania and Mania so Mania you might become psychotic and delusional Mania by definition is problematic it's causing a problem in some way or another and if you're if you have psychotic symptoms it's definitely called Mania full-blown Mania hypomania For Better or Worse is something every human being probably craves so it is it is feeling extraordinarily good it's getting by on less sleep but you don't need to sleep who needs sleep I've got things to do I am my brain is running on all cylinders I feel so creative there've been lots of famous people Through the Ages who have been bipolar you know probably bipolar and some of their most productive periods of time whether it's art or creating scientific models or what have you we probably during hypomanic episodes so what do you do in that case I mean I I'm obsessed with getting sufficient quality sleep it's a kind of a repeating theme in our podcasts and on all many of my social media posts and um I always recommend behavioral tools first then uh you know exercise viewing sunlight Etc the appropriate times avoiding late night artificial light exposure Etc um and occasionally uh for people who are doing all that and still struggle with sleep supplementation um one of the things that I've seen some data on is that for people who are following a low carbohydrate diet that inositol in particular can be helpful for getting into sleep probably because it's a bit of an has a bit of an anti-anxiety effect but presumably there are other things out there too the magnesiums will generally do that a hot bath will do that too for that matter but what you're talking about is people who are going what a day and a half without sleep or they're just you know two hours of sleep a night I have so the worst case I saw was actually a mental health professional who didn't recognize it initially he went 6 months with 2 to four hours of sleep every night because they were on a ketogenic diet he was on a ketogenic diet was getting by on two to four hours of sleep every night did not initially recognized that this was a problem he was feeling great he was feeling that keto high and he was actually waking up and like at 4:00 a.m. going for 10 to 20 mile runs most days he finally stopped the ketogenic diet after about 6 months because he said I can't maintain my weight so what you losing too much weight sorry I didn't mean to drop so what do you I was just thinking there's some social media personalities that associated with nutrition that might be hypomanic um I'll let you do the clinical uh evaluation um so what does somebody do in that case so I I don't know that I've ever been hypo manic but as I mentioned earlier unless unless I've done a very high-intensity workout early in the day and I need to replenish carbohydrates I typically eat um meat fruit and vegetables throughout the day minimum amounts of fruit but some and then at night I switch over to mainly carbohydrate it really helps me sleep it replenishes glycogen stores I sleep really well wake up the next morning repeat um and of course this goes against a lot of the Dogma that oh you're not supposed to eat carbohydrates late in the day and this is what works for me um and so and so I do it for somebody like this um mental health professional who was hypomanic would going off the ketogenic diet entirely be the best idea or could it be that um adjusting when they eat their carbohydrates would be advantageous in order to make sure that they felt alert and great during the day maybe not hypomanic but then uh you know we're could have a four to 8 Hour night sleep as opposed to a two to four hours night which is really very little sleep yeah can't be healthy it's not healthy yeah even if you can do it and feel great I imagine that the brain is suffering it is yeah and and the body is suffering I me and your friends and family are suffering the body is repairing itself with sleep and so yeah it's uh um the you know if it's somebody who's isn't not a patient they're not a mental health patient they're not using the ketogenic diet as a mental health treatment they're simply doing it for whatever um I actually start with everything you've just outlined let's start with behavioral measures first and the first intervention is education you need at least 6 hours of sleep a night period end of story that's non-negotiable if you're not getting at least 6 hours of sleep a night we need to consider this a problem so figure out a way to get six hours of sleep for some people that's enough just the education they they don't get out of bed at 3:00 a.m. it might take them an hour to fall back to sleep they fall back to sleep for most people if you can get three nights of decent sleep in a row the hypomania goes away it it it it that is the way to extinguish it and and then they still go on feeling a high from it they feel great they they their brain feels good um in terms of memory concentration motivation all of those things but they're not hypomanic anymore um and then I might use supplements melatonin others the others that you mentioned magnesium is a big one and for for some I will recommend exactly what you're doing eat some carbohydrates in the evening before you're going to bed um either have them at dinner and then wait a few hours before you're going to go to bed or have them right before you're going to go to bed just to try to calm your body down and uh get it going for when I'm using this as a clinical intervention especially with patients with serious mental illness um I actually want them in a state of ketosis long term so I'm not going to do the carbohydrate intervention I'm going to try all the other ones but if they still can't sleep even with supplements over the counter supplements then I'm probably going to go with prescription sleeping medicines as a temporary stop Gap to try to get them 3 to seven days of decent sleep that usually breaks the hypomanic cycle and then they stay on the ketogenic diet because it ends up resulting in all of these other improvements that I've described they you know they can they're illness can sometimes go into to full remission um so is it lowd dose trazodone as a first first line prescription I would not use Trazodone I would actually specifically avoid trazodone because it's an anti-depressant and they're already hypomanic and I certainly don't want to push that further so as long as it's somebody without a history of addiction I'm going to use Azo aine um or either you know commonly called the Z medicines for Sleep um zulem or ambian or something like that those tap into the opioid pathway Gaba Gaba op Gaba Gaba so I'm I'm probably I usually start with something like Adavan or clopin or something like that uh probably Adavan cuz it's shorter acting um and again I'm only looking to use it short term I let them know that up front we're looking for 3 to S days of decent sleep and then we're going to try to get them off that medicine and usually people are off to the races and can sustain it well a question about hormones um many of uh the huin Lab podcast listeners will ask anytime we're talking about something like exercise or a drug treatment or or behavioral treatment people say what about the menstrual cycle how is that impacted by this and how does this impact how does the menstrual cycle impact its efficacy Etc um carbohydrates uh and caloric restriction have been implicated in different um interaction are known to interact with the endocrine system um so what do you do if you have a patient who um is depressed or could have psychotic symptoms but let's go with depression because that's probably a bit more familiar to most people and then they're on a low carbohydrate or full ketogenic diet but their menstrual cycles cease how do you deal with those adjustments and I guess we could expand this conversation and say what about male fertility also because um subc caloric diets seem to imp my understanding is that um sub maintenance um caloric diets so weight loss diets will improve testosterone estrogen ratios in males that are obese but for someone that's not obese to go on a subc caloric diet that it can start to impair testosterone levels and and probably not make render them infertile but um certainly adjust that whole axis so what about interactions between ketosis um diets Etc and the endocrine system the real answer is I don't think anybody knows and there's not a one siiz fits-all answer cuz I've seen I've seen examples and I'm I'm aware of science to back up polar opposite conclusions um so the first general observation that I'll make I know so many couples husbands and wives boyfriends and girlfriends heterosexual couples who have tried the ketogenic diet to lose weight together and then no almost universally the men have a much easier time with it than the women um it's it's not across the board but I know so many examples where the women say I couldn't tolerate that diet it it did not make me feel better it actually made me feel worse and I think in those cases it probably does relate to hormones I'm aware of animal models of you know mice in particular ketogenic diet and mouse models one researcher shared with me the thing that was striking is that the female mice never got pregnant on the ketogenic diet whereas the mice on the standard diet were just having babies right and left and it was just shocking the difference on the surface it makes sense the ketogenic diet is mimicking the fasting state women who are trying to reproduce should not be fasting if your body is in a fasting state it probably does not want to expend resources metabolic resources calories nutrients and other things to creating a baby because your very life is being threatened by quote unquote fasting or starvation that even though the ketogenic diet is a sustainable non- starvation diet we're really using that diet to trick the body into thinking that it is in a fasting or starvation State and so just from a kind of evolutionary stance it makes sense that women's bodies may actually have significant changes in hormonal status to prevent pregnancy because a woman should not be having a baby when she's starving to death um I know of examples of women who are the opposite though who have benefited dramatically and tremendously from the ketogenic diet have put schizophrenia bipolar disorder into full remission and I do actually know of one case at least one case a woman infertile she and her husband had been trying for three years no pregnancy she went keto within four months she was pregnant how do I make sense of that I don't know and unfortunately I don't think we really have good controlled data on what does the ketogenic diet do to male hormonal systems what does the ketogenic diet do to female hormonal systems but you know clearly I think changes are happening and I it I don't I don't have a way to predict it at least if somebody else has great insights I welcome them but I haven't seen them published it's a terrific answer because when things are all over the place and bidirectional depending on one circumstance or the other I think it it screams for controlled studies and and more descriptions of case studies and and anecdotal data too so I think it's a it's an excellent answer it also um uh calls to mind the important uh public service announcement that um because of these bidirectional effects that you described U please don't use fasting or the ketogenic diet as a reliable form of contraception yes please don't I have a final question um which relates to something that is very much um starting to get buzzed now and maybe more so for people that hang out in the Twitter space or the nutrition space but um there's a new class of drugs that I think initially were developed to um treat diabetes but are now being evaluated for their efficacy to treat obes it and um these are the semaglutide um drugs that are involved in um they tap into these glucagon related glp1 Pathways and as is a um a story that we've talked about a little bit on the podcast before but many people I imagine probably haven't heard that conversation I would simply like to know what you think about these drugs um they obviously adjust the way that glucose and Insulin are managing energy um both in the body and the brain and can produce weight loss although that to me when I look at the data you know it's impressive but um a good you know a good logical shift in diet and exercise could achieve similar weight loss but a lot of people just won't do that so the question I have is um what are your thoughts on semaglutide and um other glp I think I might have said GLT before excuse me gp1 um related compounds and do you ever Pres describe these in conjunction with these dietary shifts because um it seems to me they would fall right in with the um catalog of other approaches that you have [Music] available the real answer is I am not at all an expert on these medications um but what are your thoughts about them I mean they seem to be weight loss drugs not unlike the fenfen drugs of the 90s that then were banned because a few people didn't handle them well they are and um you know in uh we had fenfen and even before that in the 1950s and 60s and70s dexadrin amphetamine amphetamine Mother's Little Helper was yes was the treatment of choice for women across the United States to keep their slim figures and we created atcts and uh all sorts of problems but they were widely used in probably millions of women because they work um because they kill appetite they kill appetite um the My overall thoughts are this there is zero doubt in my mind that the Obesity epidemic is a threat to human health and potentially the human species if it keeps going at the rate it's going it is a threat to our species we have to figure out what on Earth is happening happening and what can we do about it these medications in early studies are highly effective over a year or two that's promising I am worried though that we're not attacking the root cause of obesity and if we're not if if the root cause of obesity ends up being some kind of poisoning of the metabolic Machinery in the brain or body and I would argue that probably relates to mitochondrial health and mitochondrial function I have every reason to believe that taking a medication that helps you lose weight may not be addressing that problem and therefore may not be addressing all of the negative Health consequences of what we call obesity I actually so obesity in and of itself we know that excess fat can become inflammatory and can cause problems in and of itself but I actually see obesity as a symptom I see obesity as a symptom of metabolic derangement in the body or brain and that is why people be become obese and that if we're really going to get anywhere we need to identify what is causing that metabolic derangement using a symptomatic treatment like a glp1 you know medication to the best of my knowledge is not addressing that core problem and we're just ignoring it maybe I'll be wrong and maybe will be the wonder drug that saved the human species and everybody will be thin and healthy forever and ever I'm not hopeful because we've never we've had so many promising drugs come along fenfen dexen other things we've had so many promising drugs um and at the end of the day when you try to muck with human metabolism using a single processed molecule man-made I can't think of even one example where it's where it's been great for large numbers of people I mean certainly manufacturing insulin is life-saving for people with type 1 diabetes so that would be an example but giving massive doses of insulin to people with type 2 diabetes actually is a downward spiral I would much rather see people with type two diabetes control their diabetes through diet and Lifest style and that might be a ketogenic diet or a low carb diet or exercise or good sleep or all of the other thing all of it I'd much rather see that because when people try to control their type two diabetes with a molecule even though it's a natural molecule insulin we know that that results in really poor health consequences results in higher rates of cardiovascular disease higher rates of mental disorders higher rates of premature mortality do I think GP w you know molecules are going to be different no I don't have any reason to think they are going to be so that would be my two cents but we'll see time will tell time will tell meanwhile I want to thank you for doing what is without question pioneering work I mean I I'm again I'm not a clinician but I've been around this space long enough to know that indeed there there are no wonder drugs right there are drugs that certainly can help alleviate symptoms and um in some individuals but that lifestyle and in the case of your work in particular in the discussion today diet and the ketogenic diet in particular um it's clear can have incredible effects miraculous effects in some individuals and positive effects in others that might not be of the same magnitude but nonetheless are are extremely important so I on behalf of myself and the listeners and and certainly just on behalf of everybody out there because everyone does need to be concerned about mental health issues whether or not they have them and in their family themselves or otherwise because they impact everybody just really want to thank you for doing the work that you're doing because it really is pioneering and it's Brave and I can see now based on our discussion why it would work you've given us a lot of hints into the underlying mechanisms that suggest as to why it would work and you've G us given us examples as to how it has worked in patients that you've worked with and this field is expanding fast I think this is an area of Psychiatry and Medicine in general meaning behavioral nutritional interventions that is expanding very fast so thank you for being brave and for taking this on and doing it in such a structured way and for communicating it here today and with the general public through your book and your online presence we will certainly Point people in the direction of those valuable resources thanks so much I really appreciate it thank you Andrew for being brave and having me on your show and uh a pleasure and for uh for a great conversation thank you for joining me for my discussion with Dr Chris Palmer I hope you found it to be as informative actionable and exciting in terms of the various treatments that we can now think about when considering treatments for psychiatric disorders once again if you're interested in his work or his new book Brain energy I encourage you to go to his website that's Chris Palmer md.com you can also find the book Brain energy by Chris Palmer on Amazon and other sites where books are 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social media we are huberman lab on Instagram huberman lab on Twitter and hubman lab on Facebook and at all of those sites I provide science and science related tools for mental health physical health and performance some of which overlap with information covered on the hubman Lab podcast but often which is distinct from information covered on the hubman Lab podcast so again that's hubman laab on Instagram Twitter and Facebook once again thank you for joining me for today's discussion with Dr Chris Palmer and last but certainly not least thank you for your interest in science [Music]