Fix Your Brain by Fixing Your Body: Metabolic Psychiatry Explained by Dr. Shebani Sethi

24:25Dr. Mark Hyman:You can treat the symptom or you can treat the cause. And I think the metabolic psychiatry approach, you know, like you said, has many tools, like metformin is a drug that helps improve it. But there are many other things, right, that are including diet, lifestyle, exercise, we know is very effective for mental health. And how does that work? It may partly work by improving insulin sensitivity, right yeah that's one and you know increasing bdnf which you and i talked about last time i think on your show like now five years ago the time has flown yeah but uh you you you described it as miracle grow and i really love the way you described it because it's exactly it's exactly what it is that was one you know with exercise that it's shown to you know improve those levels and improve cognition and so forth so there's a lot of tools and the mitochondrial therapies i I mean, you know, there's a woman named Suzanne Goh who's looked at a lot of mitochondrial dysfunction in autistic brains.

25:16Dr. Mark Hyman:And whether you have ADD or autism or you have Alzheimer's or Parkinson's or depression or bipolar, schizophrenia, it's all this spectrum of brain dysfunction. And there's a lot of common pathways involved in all of these. And her work has found that, yeah, there's energy deficits in these kids in the brain. And it may show up in one subset of people as autism, another subset is schizophrenia. but essentially it's the same mechanism. You know, she talks about using mitochondrial therapies, essentially cofactors that are involved in these metabolic steps, these biochemical steps require helpers.

25:49Dr. Mark Hyman:And so they use nutrients like amino acids or CoQ10 or other compounds that actually help improve brain function. So I wonder, are you exploring any of these sort of nutraceutical approaches that are using the body's own things that uses to actually make energy, but giving them a set of higher doses or through supplementation as a tool for helping metabolic psychiatry patients? Yeah, it's an interesting question. And I love her work, by the way. And I think looking at mitochondrial dysfunction, it's a lot of shared mechanisms with these different conditions. So it does make sense when we're studying serious mental illness and other conditions to be looking at vitamins, cofactors, So we test for that in our clinic.

26:36We test for all of these things and we optimize. So we have an approach that we use to make sure that people are not deficient in these things. Because if someone's deficient, does that make sense to treat them only with medication and ignore the fact that they're deficient or malnourished in some way? if they have insulin resistance, obesity, or metabolic syndrome, sure, let's treat that, but let's make sure they're also not malnourished. Most of them are malnourished. And you mentioned 90-something percent of the population is having some kind of metabolic abnormality.

27:09Dr. Mark Hyman:They're overfed and undernourished. Right, yeah. Calories, not enough nutrients, yeah. It's almost like a crime to not be thinking about it. And that's why I think it's really important to have that approach. And to answer your question, while I'm not specifically looking at one supplement and its effect on psychiatric outcomes. I'm really looking at the whole, kind of the whole picture and making sure they're optimized. Give an example of research that's been done in our field by colleagues who looked at omega-3 supplementation, at least one gram, including EPA per day for, I think it was a total of eight to 12 weeks period, which which significantly had a good, it was modest evidence that showed benefit for psychosis, early phase schizophrenia, early phase psychosis.

28:06And it's also been a treatment as an adjunctive treatment for depression. Things like this are helpful for us to know about. Unfortunately, didn't have the same effect for chronic schizophrenia, but that's why prevention is so important. And mentioned earlier about fasting insulin, right, and development of depression. Like, why aren't we checking these things more routinely or more frequently to prevent conditions or prevent exacerbation of, you know, symptoms that are so severe like psychosis?

28:35Dr. Mark Hyman:Yeah. I mean, I think what you're bringing up is important. And, you know, medicine's very reductionist. And it likes to go, let's look at omega-3s. Let's look at vitamin D. Let's look at magnesium. Let's look at whatever B vitamins. And the body is so complex that it requires all the ingredients. It's like if you want to grow a healthy plant, you can't just have soil. You need water and light, you know, and vice versa. Like the human body is very much the same way. And I think we often will not be sophisticated in how we think about providing all the components It's needed for optimal function of mitochondria, of your immune system, of insulin resistance.

29:14Dr. Mark Hyman:And I think that one way to navigate that is sort of emerging from our understanding of metabolomics and proteomics and gene expression products that are helping us understand the body in a more nuanced way. And I think one of the things I think a lot about is what are the biomarkers of mental illness? and one of the things we should be looking at that can play a role, rather than just treating one thing, you have to find everything that's off and fix it. In other words, if your omega-3 is low and you take it, great, but if your vitamin D and magnesium are also low, might not work as well, right?

29:51Dr. Mark Hyman:And so you kind of have to think holistically about all the various factors. So can you talk a little bit about your work in the frame of the biomarkers of mental illness and what you're thinking about in terms of evaluating that. You know, you talk about lipids and triglycerides and HDL and blood sugar and A1C and all that, but it goes deeper than that. It does. And I'm glad you're pointing that out about the, you know, optimization can't just be a reductionist approach of one thing. We really have to look at everything. And that's what we are doing with our treatment approaches. It is important to, you know, obviously monitor those things as well.

30:28But biomarkers are biomarkers. In psychiatry, I don't believe that there's just going to be one biomarker. It's going to be, it's a group of markers. And thinking about certain metabolic disease states, certain conditions, how much the progression is based on those biomarkers is really where I think we're heading. And also part of the effort in our trial, we're starting a randomized controlled trial generously funded by some philanthropists, including Peace Corps Philanthropies at Stanford. And we're looking at mechanistic approaches for a metabolic intervention like a ketogenic diet in schizophrenia, bipolar, and depression.

31:13And we're looking at a lot of these biomarkers. I'll give you one example, and that is looking at triglyceride HDL ratio, for example. That's been something that has been shown with a lot of good data that depression's severity and chronicity is associated with that marker.

31:35Dr. Mark Hyman:And that's directly related to insulin resistance. So you get higher triglycerides and lower HDL and the ratio becomes higher as you get more insulin resistant. So it should be like one to one. And you can go two to one, four to one, 10 to one. If your triglycerides are 150 and your HGL is 30, that's a 5 to 1 ratio. That's not good. What was interesting about that study is that insulin sensitivity wasn't associated with the chronicity of depression, but it was for the severity. But the triglyceride-HGL ratio was associated with both. So there are some interesting nuances in the literature about kind of looking at the biomarkers a little bit differently.

32:18And I think there's a lot of different biomarkers that will be helpful. And even, for example, with insulin resistance, since we're talking about that, when we look at insulin resistance, we see that even with bipolar disorder, you have more rapid cycling, you have more treatment resistance, and you have more suicidality. So that's another thing that we could use as a biomarker as well.

32:43Dr. Mark Hyman:Yeah, I think it's so many different things. I mean, when I think about it, you want to check your nutrient levels that affect mental health, like vitamin D and homocysteine and methylmalonic acid and omega-3 fats and omega-3 index and hormonal effects like thyroid and sex hormones and your iron levels and zinc levels and insulin measurements and some resistance scores, which is now available through Quest that you do at Function Health, which measures C-peptide and insulin mass spectrometry, which is a really accurate way of measuring insulin resistance, and triglyceride HDL ratio and particle size and particle number, inflammation levels, CRP.

33:21Dr. Mark Hyman:So all these things are blood tests that actually can help clue you into many different problems. But actually, if you see there's abnormalities, and we see a lot of it, like with Function Health, we're seeing like 70 % have a nutritional deficiency at the minimum level that's actually recommended by the dietary. I'm not surprised. It's like, not like what's an optimal level of vitamin D or what an optimal level of homocysteine is, but like homocysteine levels are in the lab up to 14 or 15 and should be probably, you know, six to eight that measures your folate or B12 or B6 status. And so we're seeing a lot of that.

33:54Dr. Mark Hyman:We're seeing, you know, 95 % with metabolic dysfunction through the lipid particle size. and we're seeing 46 % with high CRPs and we're seeing a lot of really significant inflammation. So we started to go, wow, the population at large is sick. We're seeing an increase in mental illness and no one's really talked about how do we think differently about treating things systemically? And I think what you said is really important because it's a paradigm shift from thinking of the body as a bunch of different organs and parts to how the body's a network and everything is connected. and that we have to treat the network, not the symptom.

34:31Exactly, yeah.

34:32Dr. Mark Hyman:And so that's a lot of what your work is doing. And I wonder also the schizophrenia part, you know, 17 % of people with schizophrenia have elevated gluten antibodies, which can drive a lot of brain inflammation and create a lot of neuropsychiatric symptoms. Absolutely, yeah. And again, you're taking that out when you give people a keto diet, the payment part of it, you know. It's a good thing that we should test before and after too, which we're doing in our next study. So we will be doing that. And also looking at - Looking at gluten antibodies? Yeah, we're planning to. Amazing. Yeah, just looking at mitochondrial deficits too.

35:03So we'll be looking at that.

35:05Dr. Mark Hyman:So how are you doing that? Because it's something in medicine we don't really pay attention to. We learn about mitochondria in the first year of medical school. We learn about the Krebs cycle. You call the TCA cycle, which is the energy cycle, how you turn food and oxygen into energy in the body. And then we kind of forget about it. And it's not part of clinical medicine. We don't talk about how do we evaluate mitochondria, how do we test them, How do we treat dysfunctional mitochondria? Yet it's one of the central features of most illnesses that are chronic, from mental health to neuropsychiatric disorders to metabolic disease like diabetes to heart failure.

35:37Dr. Mark Hyman:Many, many problems are mitochondrial issues. Yeah, I don't have an answer as to why we don't do it more, but I think it's something that is probably difficult and hard to treat in some ways. But the more research I think that we have in this area, the better it's going to be for more targeted interventions. So I'm hopeful for that. One thing that I thought would be helpful when you're describing the mitochondrial dysfunction in various conditions, what we are seeing in psychiatry also is that the brain is volumized. It makes up 2 % of our body, but it consumes 20 % of our energy. And it's so delicate, extremely delicate, that if there are deficits in insulin and glucose handling and that, you know, Krebs cycle machinery to produce energy, then there's more metabolic vulnerability in psychiatric conditions.

36:32There's more metabolic vulnerability in specific areas of the brain. You and I talking right now, we're maybe using 80 percent, you know, our capacity. We have, if we're, you know, talking a little bit more deeper in science, you know, it'll be a 5 percent increase. Our daily, you know, activities, but less. And for someone that maybe has genetic predispositions or have environmental stress, it's going to be a little harder to have that, you know, perfect machinery producing energy. And there's more metabolic vulnerability there. And so those differences between one region of the brain and another is pretty critical for functioning, cognition, mood, and mental health symptoms.

37:13Dr. Mark Hyman:And how are you thinking about measuring mitochondrial function, as you're talking about in your upcoming studies? I believe in a lot of collaboration. I love collaborating with other scientists. So University of Toronto, Mayo Clinic, a lot of other departments at Stanford. I have a faculty member, chair of genetics, who at Stanford will be looking at all omic profiling. So all expression of proteomics, metabolomic data, wearable HRV data. Another faculty member is going to be looking at ketone metabolites because downstream of ketone metabolism, there may be, say, an amino acid called phenylalanine attached to beta-hydroxybutyrate, which is what ketones will break down into.

37:57And if you have that, the end effect of appetite reduction or weight loss is present. If not, it doesn't work as well. The mitochondrial testing is a collaboration with Mayo Clinic and University of Toronto. and that's looking at all the different metabolites in the mitochondria. Lactate's one of them, but there are a lot of other, there's sexinil-CoA, different dehydrogenases. So we'll be looking at all the levels of that.

38:22Dr. Mark Hyman:That's not something you normally can get at a regular lab test. No. Is there a research-based test looking at mitochondria? Yeah. I mean, clinically, it's been a tough thing for us to look at because you could do a VO2 max test, which is basically an exercise treadmill test that measures sort of indirectly your mitochondria. you can measure organic acids, which are urinary metabolites. And I think, you know, we all have sort of subtle changes in our metabolic pathways that affect different things. And we can see some of those changes, but there's now, you know, cheek swabs that look at the respiratory chain, which is, you know, basically the assembly line that turns food and oxygen into energy.

38:54And there's some interesting, you know, kind of ways to start to think about how do we sort of

39:00Dr. Mark Hyman:clinically measure this in people? Because it's such a big, it's such a big black box and it's so important. And then you can actually even be specific and say, oh, this pathway that requires CoQ10 is a little slow. So what if I give extra CoQ10? It's going to speed it up. And it becomes more personalized that way, right? And more specific. And I forgot to mention, we're also looking at epigenetic data. So looking at DNA methylation and gene expression, it's 120 patients, randomized control trial, and we'll be collecting a lot of data, continuous ketone monitoring. Abbott donated the devices. Glucose monitoring.

39:35grateful for that. Yeah. Glucose monitoring and getting more. We're still fundraising for the trial, but we have gotten enough to get started and we're looking at all these measures and it's exciting. We're excited about it.

39:46Dr. Mark Hyman:You know, what you're offering to people is not here, take this pill for your mental illness, but here, here's a lifestyle change that can have profound effects. How do you do that? Because these are patients who are often mentally ill, which makes it harder for them to make good choices, right? And so you're asking them to do a ketogenic diet or you're asking them to do severe lifestyle changes. How are you getting people to do that? Yeah, that's a good question. And, you know, I do want to recognize that it's not always easy, especially when you have a condition like schizophrenia. But there's a lot of support that is involved in providing care that's important in those cases and caregivers that get involved.

40:27So we do support groups. We really help them with, you know, adjusting to making changes in the home to be able to not necessarily thinking about it as a diet, but really think about it as a lifestyle change and a metabolic therapy for their illness, which is improving their quality of life, which is our primary outcome is the thing we care about most as clinicians. Right. So, you know, we, we want them to have a better quality of life. They want a better quality of life. And that's what also motivates them to stay on, on the, on the diet or the approach as well. Yeah. So I think a combination of that.

41:00A lot of good side effects, yeah. Yeah, a lot of good side effects, yeah.

41:04Dr. Mark Hyman:I mean, in your clinical trial, you did a ketogenic diet for bipolar and schizophrenia that recently published with 20 few patients. You had 100 % reversal of the metabolic syndrome or prediabetes. You had 12 % reduction in body weight. You had a 36 % reduction in belly fat, 27 % reduction in insulin resistance, which by the way, the HOMA-IR probably not as good as this new insulin resistance score that Quest is doing through the last spec. We're doing that now, yeah. But, you know, dramatic reductions in psychiatric symptoms and so improved sleep, life satisfaction, all these great side effects, you know.

41:40Yeah, in four months.

41:41Dr. Mark Hyman:Yeah, and when you're taking a drug for schizophrenia, all the side effects are bad, right? You know, all the side effects are good. And does that encourage people to stick with it more because they're seeing the positive effects? It does encourage people to stick with it more. And I think, you know, over time also organically, the more mutual patients with other clinicians in cardiology, endocrinology or primary care see their patients improving with reduction in visceral fat and improvement of, you know, other metabolic markers aside from the psychiatric markers. and people start to appreciate it and are grateful that their patients are doing better.

42:20And the patients themselves also themselves feel like they have more control over their life. It gives them hope. And a lot of the patients that were in that pilot study that I did was published last year, but are still in my patients today. A lot of them are still in my patients today. And a lot of them are still on a ketogenic diet. So it does speak to, I guess, the feasibility of being on it over time. And I said earlier that my goal was, I like seeing patients. I enjoy seeing them get better. A lot of these conditions are hard to treat. Having a tool like this and seeing that it's helpful is very encouraging.

42:55I thought that doing research is important for our field in order for it to, you know, go past just beyond me and other people do it. I don't want it to just die with me. I really want this to be out there. so when I'm not around, my son can grow up in a world where there are more things at his disposal and that my patients have at disposal and people that we can reach beyond just the academic centers, beyond research. I think that's why it inspired me to go outside of that too and start something and found a company that's really just focused on providing that care because otherwise research just stays in research and in academia.

43:38It doesn't, not going out doesn't feel right to me, I guess.

43:42Dr. Mark Hyman:I mean, it takes decades for scientific discoveries to end up in clinical practice. So I think the fact that you started Menobox Psychiatry Lab, which is an online platform for engaging people who want to try this out is important. And it allows it to scale up and people to get access to it. And what you're doing is so revolutionary. I mean, think about the fact that, you know, nutrition has not been a topic in medicine that is really thought to be a serious subject. And it's sort of stepchild, fourth cousin, once from who. Not science enough. Yeah, but what you're talking about is a nutritional therapy that has effects at orders of magnitude more than our traditional therapies.

44:23Dr. Mark Hyman:So it's not like it's an equivalent therapy. It's so much better. And I wonder if in terms of your work at Stanford, Are you finding resistance or are you finding encouragement or openness to this idea? Because it's sort of a... Yeah. A lot of people ask me that question and I appreciate that. I have found a lot of support. With anything, there's always waves, right? But I have found a good amount of support, especially with all the activities I'm involved in. And I'm in Palo Alto, Silicon Valley, right? It's pretty common for professors to spin out companies outside academia as well. I love doing the research.

45:04I believe it's important to have evidence-based science. So I'll still continue to do that. But also, you know, having the support to be able to move between these worlds is something that I'm grateful for.

45:18Dr. Mark Hyman:And so your psychiatry colleagues are not going, what are you doing using food in medicine? You should be using drugs? I think some people are like, how do you stay on that? How do you stay on a ketogenic diet, right? But again, I think it's the way you approach it. I think understanding, I think education, understanding around, it's a therapy, not a diet, really. In my mind, it's really a therapy, just like a drug would be. It requires monitoring, it requires a physician or someone trained in that area. And there are other metabolic tools. I wrote this in a nature paper along with 12 other authors focused on, you know, what is metabolic psychiatry?

45:58Why is this important? But also what are the what is the current evidence for these different metabolic based treatment interventions? And why should we care? And where are we going in the future? I'm more hopeful because there's a global group of scientists and researchers that do care about this and are working on this. And I think it was just yesterday that the Senate Appropriations Committee came out with a recommendation for the NIMH to put more money and funding into, guess what, nutritional science or nutritional ketosis work in serious mental illness specifically. I'm psyched about that.

46:33I can't wait to apply. and I hope that I can do more research with metabolic psychiatry labs or at Stanford. But I care about the science and I care about patients getting access to these treatments. And so, you know, I love that Function Health has been able to really improve the access to get these labs. And what we're doing at metabolic psychiatry labs is putting together the biomarkers, the personalization, using AI, machine learning algorithms to improve the disease states of someone with schizophrenia versus someone with bipolar, and really provide that wraparound care for them, and work with their psychiatrist or their therapist or their PCPs so that they're not alone in this whole world, and I think, or in the healthcare system, which I don't know how much we want to go into that, but I wanted to share with you that the reason why I was, I think, compelled or felt obligated to go in this, is myself, after I had a child, I had a really significant tailbone injury, and I couldn't sit for nine months.

47:40And so, yeah, it was horrible. But a lot of people couldn't see that I was injured or suffering in some way because, you know, I wasn't walking around with a cast or, you know, I didn't have, it was invisible, right? There was a colleague of mine that sent me a book on tailbone pain. And there was a chapter on the psychology of tailbone pain. And when I read it, it just felt so validating. It was like an advocacy of how do you walk through the healthcare system and how do you tell your OB-GYN or what the issue is? Because it gets often missed. It was so helpful for me, that book. So I decided that I wanted to do something similar, like a patient advocacy manual or book.

48:22And I'm still writing it and who knows when I'm going to be done. But I wanted to do that for those with serious mental illness. Starting metabolic psychiatry labs is part of that reason.

48:30Dr. Mark Hyman:And you're starting with the most extreme case, right? Schizophrenia, severe bipolar disease. But the spectrum of mental illness goes from just a little anxiety and depression to OCD to more serious things. So across that whole spectrum, this approach can work, right? It's not just serious mental illness. It can be depression, anxiety that may be less severe, but still debilitating for someone and they're suffering from it. And having a metabolic approach, especially if 90-something percent have metabolic abnormalities, why couldn't they not benefit from something that's tangible and targeted and specific and evidence-based?

49:17Dr. Mark Hyman:I mean, it's really interesting because I first started to understand these ideas when I was treating people a lot of chronic illnesses that were not really psychiatric in nature, like an autoimmune disease or insulin resistance or microbiome issues or gut issues. And all these psychiatric problems would go away or get better. And I was kind of like sort of shocked. And it's really why I wrote this book, The Ultra Mind Solution, How to Fix Your Broken Brain by Fixing Your Body First, because I was like, wait a minute, nobody's talking about this. And I don't know if this as a thing or not, but it's certainly repeatable in my practice.

49:52Dr. Mark Hyman:And if you pay attention and observe what's happening with your patients and listen to them, it's like, holy cow, you know, you treat someone's microbiome and their OCD gets better, or you treat someone with some nutritional deficiencies and they get better, or you fix their blood sugar dysregulation and their anxiety goes away and their panic attacks get better. And like, okay. And see, I think the reason why you ended up maybe putting that together is because you're probably, you know, you were treating patients, you were coming up with something for them, you saw them get better, and it went from there.

50:25And I think really where the heart is of, you know, when you're really seeing patients and treating them, you see that. Probably motivated you to do what you're doing today. Totally.

50:33Dr. Mark Hyman:I mean, I jokingly call myself the accidental psychiatrist because I just didn't treat people's mental health issues, but then I started to, and then I wrote a book, and then boy, I got a flood of patients who had mental health issues and autism and add and alzheimer's you're trying to find solutions and they and it was amazing to see how much they got better when we just apply this sort of systems approach to dealing with all the variables that go wrong and not just being a reductionist sort of single vector i think you'll be excited to know that we're also looking at microbiome we're testing the microbiome also before and after with the trial.

51:12So genetic, you know, data too. So it's really like a big library of data that we'll collect and happy to collaborate. Yeah.

51:21Dr. Mark Hyman:Very fascinating. I mean, I think, you know, our data set is function health is interesting because we won't share it or sell it or use it for any purpose other than, you know, just helping learn. And, you know, anything we learn will be from an anonymized data set that you can't tell who's who. But we're learning so much about the population, and it's going to be an interesting strategy to how do we start to study what's happening. And we actually had a talk with Lloyd Miner, who's the dean of Stanford, about collaborating on some research projects. Oh, good. Because, you know, it's hard to do a study.

51:54Dr. Mark Hyman:I mean, you want to do a study with 120 people. It is. It's millions of dollars. It's a lot of effort, and, you know, the costs are really high to do the diagnostics. But here we have almost 300 ,000 members and hundreds of biomarkers on each one, which is tens of millions of biomarkers. It's a really good way to collaborate. Literally, we have available to sort of figure out what's happening with the population when they change things or do this. And I think it's going to be an interesting data set. Absolutely, yeah. We should talk more about that. I'd love to. Actually, Lloyd Miner is a huge supporter of the work and actually wrote me a very nice email after the pilot study came out and was really grateful for what I was doing.

52:36So it's very encouraging. That actually answers your other question about how supportive is Stanford.

52:42Dr. Mark Hyman:I think people who have an open mind, I found this at Cleveland Clinic, that, you know, people who were in these sort of elite institutions typically had more open minds because they were curious. They were asking questions. They were willing to challenge orthodoxy. And, of course, there was always the pushback. But this is this sort of weird moment in psychiatry where I think we're kind of converging these two massive paradigm shifts. One is around psychedelic medicine, trauma, and then metabolic psychiatry at the same time. And I feel like they're complementary. I'd love to see them sort of combine all the pieces because, you know, you can't just do one thing.

53:21Dr. Mark Hyman:Like, you know, if you have some serious trauma, yes, you have to fix your metabolic function, your nutritional status, get your thyroid working, get the toxins out of your system, then your brain can work better. Right. I always say it's a lot easier to be enlightened if you're not mercury poisoned or your thyroid's working, you're going to be trial deficient, right? Absolutely. But if you also have to look at the other end of the equation, which is, you know, one of the psychological impacts that imprint on the brain and on our genes and epigenetics that actually drive our psychiatric symptoms.

53:53Dr. Mark Hyman:So it's sort of bi-directional and you can't kind of do one without the other. You know, one of the things that you talked about is eating disorders. And I was sort of curious about that because the orthodoxy in eating disorders is don't restrict anything for these often young girls, sometimes boys. And yet you're talking about putting these kids on a ketogenic diet, which is extremely restrictive, right? So what have you found with these? Yeah, I have some colleagues. This is one of the most life-rending illnesses is anorexia. I have a colleague who's doing a trial looking at ketogenic diet and anorexia specifically.

54:30You know, as a whole, when we look at eating disorders, whether it's anorexia or bulimia or binge eating, there are disruptions in several different pathways. There's serotonin, dopamine, and opioid pathways as well. A lot of the literature on anorexia and restriction has been largely, and with Blymia too, is that you would exacerbate the symptoms when you're restricting a diet. But a lot of that literature is based on low-fat, low-calorie diets. Not necessarily thinking about, well, if you add fat back in and you have moderate protein and you nourish yourself in kind of the right way. So to me, it's not a diet.

55:14It's actually the way we should be eating more like this. Is that changing neurocognition? Is that changing the obsessions or compulsions, for example, that you sometimes do see in anorexia and the rigidity? And that data isn't quite out yet, but there is some preliminary data that is showing improvements, especially with binge eating and bulimia. We published some case series on this and recently published an article a couple weeks back on improvement in food addiction symptoms, which is a separate clinical entity from binge eating disorder and obesity. But it tends to be in a subgroup in both conditions, and in that subgroup tends to be worse outcomes.

55:56when you have the food addiction as well. So there are reductions in binge eating and purging and, you know, so forth. So we, you know, we have been looking at that and researching that data.

56:07Dr. Mark Hyman:But it's not easy to do a ketogenic diet. That's the hard part. It's like you have to get rid of grains and beans and sugar. And it's a personal choice. If someone wants to go down that path, you know, we will support it as long as it's clinically appropriate for them. I did a trial in the past with a colleague of mine, Debra Safer at Stanford, which we looked at an obesity drug, FDA-approved obesity drug called casimia, and we looked at that in binge eating disorder and bulimia and achieved abstinence rates of 63 % while on the drug versus the control group was about 6%. So there was a pretty significant difference between those that were taking the medication because it affects reward pathway, it affects glutamate and GABA transmission, it was shown to be helpful for them.

56:56Dr. Mark Hyman:That's amazing. Where are the big gaps in our knowledge that we have to fill in this field? How do we do the types of studies that are needed? Because, you know, I remember Thomas Insull, who I met once, who was the former head of the National Institute of Mental Health. I said, what do you think of the DSM-5, which is the diagnostic and statistical manual that you use to describe psychiatric illness? And essentially, it's describing symptoms and categorizing people according to their symptoms, not causes. He goes, well, I think it has 100 % accuracy, but 0 % validity. Meaning it's great at putting people in categories of symptoms, like you have schizophrenia, you have ADD, you have bipolar disease, you have depression, you have anxiety, you have OCD, but it doesn't tell you anything about why.

57:38Dr. Mark Hyman:And also it doesn't help you differentiate in those groups, the different causes, because you could have 10 people with depression with 10 different causes and you need We treat each one differently instead of this one-size-fits-all medicine, which is kind of what we do. Yeah, I remember him saying that before, too. And, you know, he's right. It's one way that we have as a field to categorize the symptoms. Where we would like to go is, you know, you talked about biomarkers earlier and thinking about what are the right biomarkers. Yeah. And, you know, what's the right way to have a tool that you can predict certain symptoms arising?

58:15and thinking about the metabolic pathways that are involved, specifically looking at more mechanistic understanding of that energy vulnerability and differences in diagnosis and disease state can be helpful. But again, there's a lot of shared pathology, shared characteristics, and thinking about more of that root cause of what are the dysfunctions and why it's occurring, and is it happening in all conditions? A lot of times with psychiatry, there's a lot of different causes and it's heterogeneous, okay? And so it can be quite complex. But I think the more targeted we can be and the more specific we can be with our treatments, who's gonna do better on what treatment?

59:02I think that's where we wanna go in collecting our data. So with the data that you guys are collecting with labs and the outcomes and the treatment, you know, that we're collecting, I think that would be a really good way of figuring it out.

59:15Dr. Mark Hyman:A hundred percent. I mean, and we're seeing this convergence of like the understanding of sort of the measurement of our sort of different metabolic pathways that are off, but also sort of the personalization. So we sort of combine metabolic psychiatry with personalized psychiatry. It becomes much more effective. More precision, yeah. Right. And I think that's what I've always done with functional medicine is, you know, everybody's got a different treatment, even if they have the same disease, because it depends on what their particular dysfunctions are. And you can actually assess those and measure those.

59:48Dr. Mark Hyman:We can look at the microbiome. We can look at the mitochondria. We can look at, you know, the gut and food sensitivities. We can look at nutritional status in different people. We can look at toxin load in different people. We can look at all these different things that play a role. I think we need to sort of better accelerate this because so many people are suffering. And, you know, around the margins, there's these cracks in our conceptual framework in medicine. There's a crack in the ideas that we all were trained in medical school, which is that diseases are these entities that show up that we have to treat with drugs that we don't really know why they happen necessarily.

1:00:25Dr. Mark Hyman:And we don't understand the causes and we just kind of have to do our best downstream. we have to get to upstream medicine, root cause medicine, systems medicine, network medicine, whatever you want to call it. And I think the work that you're doing at Stanford around metabolic psychiatry kind of breaks that through, but it's true across all of medicine. This cracks are happening everywhere, whether it's autoimmune disease or neurodegenerative diseases. The thing that I think people are wondering about, I'm sure if you're listening, is where do I start? How do I, like, I'm depressed, I'm anxious, maybe I have bipolar disease, maybe I've got a form of schizophrenia.

1:01:01Dr. Mark Hyman:Like, what do I do? What would you advise people to? First, understanding that there are tools out there right now that can be delivered and over time, obviously, will be refined and improved. But that there is a place to go to get care. We have a, you know, we have a line for people to contact us. We will recommend where we think it makes sense for them to get care. We offer care both at Stanford and at metabolic psychiatry labs. And so there's a lot of, you know, research trials. I'm involved in several now. So that's also an avenue that patients can take. Hopefully we can get to a place where I have a manual recommendation where they can kind of navigate.

1:01:45But for now, I've been able to set up, you know, a line where people can contact and get information. And if they want to enroll in care, they can. Not bound by a geography, not bound by one academic center, right? And it's scalable and digital. Yeah, every state.

1:02:01Dr. Mark Hyman:And that's the metabolic psychiatry labs. Yeah. And is that operational now? Are people able to join? It's operational. It is venture-backed and it is going to grow. That's pretty exciting. I mean, because I think talk therapy is helpful, but it's not going to fix people if they don't have these underlying things. No, it's just one tool. So I think we have to use all the tools in our toolkit, whether it's trauma-informed therapy, whether it's psychedelic medicine, whether it's metabolic psychiatry, nutritional psychiatry, microbiome psychiatry, I don't know what you want to call it. Integration.

1:02:34Dr. Mark Hyman:The job guy always says, you know, your psychiatrist doesn't check your poop test when you go to the doctor and you have depression, but they probably should. And I actually, speaking of the microbiome, I don't know how much you're looking at that, but it was such a huge unlock for me to understand when we looked at people's bowel overgrowth of bacteria or various metabolites, you could check in organic acids and you would treat them. And sometimes I would treat psychiatric problems with antibiotics. You clear out bacterial overgrowth or fungal overgrowth and people would come back to life. I remember this little girl I had who was a beautiful nine-year-old little girl who was, just a terror.

1:03:13Dr. Mark Hyman:And she was kicked out of her class like routinely in school on the bus ride home. They have to stop the bus 15 times to deal with her disruptive behavior and violence, aggression. I did a urine test, which looked at metabolites of bacteria and yeast in the gut. And she just was off the chart, like with fungal metabolites and bacterial metabolites. And so her gut and give her an antibiotic and an e-fungal and give her some probiotics. Good she had you. It was like the lights just came on in this girl overnight. She went from like this terror to being this sweet little girl. Yeah. And I was like, oh, wow, this is more here than I understand in terms of what's affecting the brain and how the brain responds to different things that are happening in the body that we haven't really begun to uncover.

1:04:06Dr. Mark Hyman:And so I'm excited to see, you know, 20 years later, now this is actually emerging. as a field of inquiry, as something that people are paying attention to in major academic centers like Stanford. It's pretty exciting. It's about time, right? It's about time, yeah. It's about time. Actually, the PANS autoimmune with OCD and depression. Pandas. Pandas, yeah. It's a, call it PANS clinic at Stanford. But I've seen a lot of cases there where antibiotics are really helpful for the psychiatric symptoms. Yeah. There was another biomarker like L-acetylcarnitine that my colleague actually at Stanford had looked at as a marker of depression.

1:04:43And with slow on depression, and so with antidepressants, it resolved the marker with treatment response.

1:04:53Dr. Mark Hyman:You mean like SSRIs improve carnitine levels? Interesting. Yeah, the acetyl L-carnitine level, yeah. So it's interesting that we might be giving drugs thinking they work one way, but they might work another way. Statins may not really work by lowering LDL, but they work by lowering inflammation. Exactly. Exactly. So that's why metabolic psychiatry is really thinking about the whole picture and that there's multiple tools, both with medication and nutrition and how it all gets put together. Yeah. And I'm excited doing the omics work and deep metabolomics and mitochondrial testing because before we really had a hard time.

1:05:29Dr. Mark Hyman:Like it was like it was like looking at the sky without a telescope and or looking at, you know, bacteria without a microscope. So it's hard to see. And now with the advent of deep diagnostics that are available, not just regular biomarker testing, but looking at what we call the omics, which is your metabolomics, all the metabolites you have in your blood, the proteins you have in your blood, proteomics, epigenetic expression. we can start to map out what's happening and see these patterns and then use AI and machine learning to help us make sense of them and then kind of see how we can create more targeted solutions for people based on these large data sets which are becoming radically deflationary.

1:06:12Dr. Mark Hyman:I mean, I think your whole genome sequence you can do for 300 bucks an hour used to be a billion dollars. That's a big drop in price. Yeah, so we're poised at a very good time right now to be able to use technology to really understand, you know, the science and the mechanisms. And it's not just the sky, there's a whole universe now, right? Between the, you know, breaking down of food and production of energy and waste products, what we call metabolism, right? So there's a whole universe out there and excited to continue to explore it. Exciting work. I'm going to keep following what you do. I'm going to maybe see if we can work together to figure out the mental health biomarkers.

1:06:47Dr. Mark Hyman:That would be something, right? And go see a psychiatrist to make a standard of care to get a panel of biomarkers for mental health, let's make sure you don't miss anything. Yeah. You know, it's amazing. I'd love to. I mean, it really takes multiple brains and energy since we are all in limited supply to create something really wonderful. Well, thank you. How can people learn more about your work? Metabolicpsychiatry.com or metabolicpsychiatrylabs.com is the two websites. It's a free resource. Metabolicpsychiatry.com is a free resource through Stanford that we created and happy to help anyone looking for anything specific.

1:07:23And metabolicpsychiatrylabs.com is, of course, the virtual remote care for metabolic psychiatry care that's nationwide.

1:07:31Dr. Mark Hyman:And then for those nerds listening, there's a great article that you've written called Metabolic Dysregulation and Metabolism-Based Approaches to Mental Health, a narrative review of metabolic psychiatry, sort of trying to lay out a whole field, what it is, what we know, where we are now, What are the options for therapy from nutrition to metabolic therapies to drugs that can modify these pathways? And I think everybody should have a good look at that paper. We'll put it in the show notes so we can track it. Thank you for your work. I'm going to keep following what you're doing. We'll have you back maybe in a few more years.

1:08:01Dr. Mark Hyman:Another five years. That's what's happening next. I really appreciate what you do in the world. Yeah, likewise. Thank you for having me, Mark. If you love this podcast, please share it with someone else you think would also enjoy it. You can find me on all social media channels at Dr. Mark Hyman. Please reach out. I'd love to hear your comments and questions. Don't forget to rate review and subscribe to the dr. Hyman show wherever you get your podcasts And don't forget to check out my youtube channel at dr. Mark Hyman for video versions of this podcast and more Thank you so much again for tuning in.

1:08:29Dr. Mark Hyman:We'll see you next time on the dr. Hyman show This podcast is separate from my clinical practice at the ultra wellness center My work at Cleveland Clinic and function health where I am chief medical officer This podcast represents my opinions and my guests opinions neither myself nor the podcast endorses the views or statements of my guests This podcast is for educational purposes only and is not a substitute for professional care by a doctor or other qualified medical professional. This podcast is provided with the understanding that it does not constitute medical or other professional advice or services.

1:08:58Dr. Mark Hyman:If you're looking for help in your journey, please seek out a qualified medical practitioner. And if you're looking for a functional medicine practitioner, visit my clinic, the Ultra Wellness Center at ultrawellnesscenter.com and request to become a patient. It's important to have someone in your corner who is a trained, licensed healthcare practitioner and can help you make changes, especially when it comes to your health. This podcast is free as part of my mission to bring practical ways of improving health to the public. So I'd like to express gratitude to sponsors that made today's podcast possible.

1:09:28Dr. Mark Hyman:Thanks so much again for listening.