In this episode we discuss:
- Recent studies on the relationship between ketogenic diet and mental health conditions
- The mechanics of how ketones affect the brain
- Considerations for treating mental illness in kids and teens
- What are the target therapeutic ketone levels and how supplementation can help
- Using ketogenic diets to address behavioral disorders
Show notes:
Hey everybody. Chris Kresser here, welcome to another episode of Revolution Health Radio. I’ve talked on the show before about the link between metabolism and mental health. In fact, I had Harvard psychiatrist Dr. Chris Palmer, who’s been a pioneer in this field, on the show, to talk about metabolic psychiatry and his brain energy theory of mental illness.
So I was really excited to welcome Dr. Matt Bernstein as a guest on the show today. He’s a psychiatrist as well. And in fact, his initial exposure to the idea of a link between metabolism and mental health came from listening to a lecture from Dr. Chris Palmer about 10 years ago. He had two of his sons [who] were struggling with mental health conditions related to mold and Lyme, and was not finding any answers within his own profession of psychiatry and within conventional medicine as a whole, and heard Chris Palmer’s lecture. That really opened up some doors for him and led him down the path that he has been on for the past several years, which is treating patients with mental health and behavioral disorders with a ketogenic diet, with great success. He’s actually started a residential program called Accord in the Boston area that helps people to implement this approach, and is having remarkable success, which we talk about in the show.
We cover the evidence behind a ketogenic diet and mental health– what’s happening in the brain in mental illness, mechanistically, and why providing ketones addresses that, how ketones improve mitochondrial health in the brain, [and] what populations and different conditions benefit from this. We talk a little bit about kids and teenagers and young adults and specific considerations there. I really enjoyed this episode. I think it’s going to be super helpful for all of you listeners, anyone who is suffering from mental health or behavioral issues themselves, or parents who have kids or teenagers that are struggling with these issues. So without further ado, let’s dive in.
Chris Kresser: Dr. Matt Bernstein, it’s a pleasure to welcome you to the show.
Matt Bernstein: Thanks for having me.
Chris Kresser: I’d love to start by learning a little bit about what got you interested in the metabolic approach to psychiatry and mental illness in the first place. I had Dr.Chris Palmer on the show a while back. I know he is a colleague in your space with a similar interest. And I’m just curious what led, over your career, to this focus?
Matt Bernstein: Yeah, always a good question. So, there’s lots of length versions of the story. I’ll give you the sort of shorter one at this point. At the time, I had two kids. We have three boys, but two of them had gotten sick with a pretty unexplainable illness, which we later figured out to be autoimmune encephalitis from mold and Lyme. But at the time, we didn’t know that. So I’m sitting, with all of this in my mind, trying to figure out what’s going on with my kids, and regular medicine wasn’t helping them. And I’m in a Grand Rounds lecture. Actually, Chris Palmer was giving the Grand Rounds about using the ketogenic diet to treat treatment resistant schizophrenia and bipolar disorder. And I was very receptive to the message at the time. I think I may have been one of the only people in the audience who actually understood and believed what he was saying. Because it was a pretty skeptical crowd, I think.
Chris Kresser: Were you receptive because of your experience with your sons? Or were there other things in your career, like maybe the traditional approaches to treating mental illness were not as successful as you’d hope they would be in your patient population?
Matt Bernstein: Definitely both. Yeah. I mean, I’ve always worked with people with more severe illnesses, and I always have my eye on people really getting back to life, having a functional outcome, as opposed to just reducing symptoms, which is what generally mainstream medicine cares about. We measure these symptom rating scales in psychiatry, and we say this drug works if you can reduce the symptoms. But it doesn’t take into account all the side effects, metabolic effects that are happening, which eventually end up leading to, even if the symptoms are better, the functional outcomes are not very good most of the time, meaning people are not getting back to work. They’re not getting back to living independently. The best we can hope for sometimes, in these more serious illnesses, in the mainstream approach is keeping someone out of the hospital and keeping their symptoms a little bit lower than they were. But unfortunately, tremendous amounts of metabolic side effects, often huge amounts of weight gain, diabetes, 10 to 20-year earlier mortality than the general population in that population of people. So I was always noticing and very disappointed by all of that. And then, of course, with my kids’ experience where we got really no help from mainstream psychiatry and mainstream medicine in general, I was doubly receptive at that point, I think.
Chris Kresser: Yeah, this is what I call disease management versus healthcare.
Matt Bernstein: Exactly, right, exactly.
Chris Kresser: Yeah. So, okay, so you were exposed to Chris Palmer and his work, you were very receptive to that. And then I imagine that took you down a path of, wanting to confirm and verify that in your own experience.
Matt Bernstein: Absolutely, yeah, yeah. First, immediately, put myself on a ketogenic diet. Felt amazing, but we were still really in the thick of it with our kids. Our kids weren’t getting better yet, so we had a lot of work to do on that front. So I really wasn’t ready to bring it into my practice quite yet. This was about, I don’t know, eight years ago or so. Fast forward a few years, our kids got a lot of help through Functional Medicine and Environmental Medicine, and I started having the bandwidth to start really researching this and figuring out how to apply it with my patients, and figuring out what actually works, and what, not only what works, but what really works in the real world, what can they actually do? And so that led me on a journey of trying to figure out and hone various protocols for people using this incredibly powerful connection between metabolism and brain health and mental health.
Chris Kresser: So let’s double-click on that. I’m curious how you look at this at this point. Is that the main, or even exclusive lens that you look at mental illness through? Or is it, sort of one of a few that you found to be really helpful? In my mind, I’m thinking about, for example, the inflammatory cytokine model of depression, which is often triggered by gut microbiota imbalance and intestinal permeability, which then leads to a systemic inflammatory response. Do you include that in this overall frame? Or would you kind of put that in a separate bucket?
Matt Bernstein: No, it’s included in this frame, I think, because what I’m advocating is people not only eat a diet that produces ketones, but that it’s a well formulated version of that diet, so that we do need to heal the gut as well. And there are lots of good, there’s lots of good science about how the ketogenic diet works in epilepsy, because it’s been used in that illness for many years. And one of the main mechanisms is actually through the microbiota, gut-brain axis. And so, just eating a diet, if you eat junky keto food, and get into ketosis, you’re not going to have the same outcomes as if you eat a whole foods version of this. And I do advocate for people who can tolerate it, definitely including a lot of plant material in the diet that produces ketones as well. Because I think if it’s tolerated, then you’re going to all these additional improvements with short chain fatty acids and polyphenols, and all the magic that all of those things do for both the gut and the gut-brain axis.
Chris Kresser: So given that, that you would include that in the frame, would you say that all mental illness has [a] metabolic issue at its root?
Matt Bernstein: I would say it’s the biggest factor in brain health that I have found, and it’s the most powerful way to affect brain health that I have found. It’s not to say that just a well formulated ketogenic diet and improving metabolic health is going to cure everything. I don’t want to overstate it. There are people who, that’s one piece of the puzzle, and we do need other pieces to fall into place. But it is so powerful, and it’s such a great foundation to start any further healing journey, because one now has the mental capacity and physical capacity to engage in all of those other therapies. One of the big, and we have a lot of good therapies in mental health, psychotherapies and various other types of therapies. But people are often so symptomatic and also so metabolically compromised, their energy is so compromised, they have brain fog, they can’t engage in these therapies. And so if we start here, many times things fall into place, but if they don’t, then we at least have that foundation, we have the energy to engage in whatever else is necessary to sort of finish the process.
Chris Kresser: That’s a really good point. I’ve thought about this a lot in the case, in my practice, and working with people with psychological issues is there’s often a downward spiral where the depression and anxiety, whatever, and then that gets in the way of all of the practices that contribute to mental health, like exercise, good sleep, good diet, etc. And so it’s always the trick is, how do you reverse that and create the upward spiral? Because, as you pointed out-
Matt Bernstein: That’s exactly right.
Chris Kresser: You can look at study and see that exercise is comparable to or superior to antidepressant medication, but it doesn’t matter if the person is so depressed that they can’t exercise or they won’t exercise.
Matt Bernstein: Absolutely, yeah. It’s exactly right, yeah, we see these downward spirals, and then it includes not just not engaging in these important practices that you describe, but also relationships falling apart, work life falling apart, the stresses pile up, the depression gets worse, and that spiral just can keep going down. But this is such a powerful way to reverse that and start getting the spiral to start moving up and start building off of that.
Recent Studies on Ketogenic Diets and Mental Health
Chris Kresser: So I was quite familiar with the literature on ketogenic diet and mental health up until maybe two or three years ago. I haven’t been paying as close attention recently. So what does that look like over the past few years? Is there a growing number of studies looking at these relationships? And tell me about maybe what, summarize the state of the evidence, so to speak, behind ketogenic diet and different mental health conditions.
Matt Bernstein: Yeah, there’s continued to be a lot of research being published in the last few years. We can start with a study from 2022 that came out. It was an inpatient psychiatrist in the south of France who put a bunch of people on his inpatient unit who had been hospitalized many times. These are people with schizophrenia, bipolar disorder, major depression, put them on a well formulated ketogenic diet, a few supplements, nothing fancy at all, like real basic stuff. The outcomes were absolutely unbelievable. He was able to lower their psychiatric medication, their rating scales, they had effect sizes above three in all their psychiatric rating scales. And for people who don’t know what effect sizes are, antidepressants come in at about point three five, antipsychotics come in at about point six. These are three to 3.5 effect sizes in depression, scales, psychosis scales, the CGI, which is clinical global impression. So really, just fantastic sizes, effect sizes.
Chris Kresser: Can we just linger on that for a second? You’re saying that the effect size was tenfold greater with a ketogenic diet than with SSRIs.
Matt Bernstein: That’s exactly right, although, we have to, the caveat is that this is an uncontrolled study, and so is retrospective. So it’s not the RCT that a lot of people are looking for. However, just that, anyone who can get someone who’s been that chronically ill that well and do it in a whole series of people, I mean, that intervention is something we all should be paying great attention to. So that was a really cool study. That got a lot of people’s attention. And then there’s been some other ones. Dr. Shivani Sethi from Stanford published a pilot trial in people with bipolar disorder and schizophrenia. These were outpatients, and they didn’t give them the diet. They actually just taught them how to do it. So it proved feasibility also complete reversal of metabolic syndrome, and everyone who had metabolic syndrome in that study. We had amazing results, in terms of everyone who was fully adherent to the diet had full remission of their psychiatric symptoms. We had improvements in sleep, improvements in overall functioning. I mean, everything they measured got better. So again, that was again, maybe 20 something people, but not controlled, but again, really astounding results.
And then another one at the University of Edinburgh, Ian Campbell and his group, they had all bipolar people in this study who are stabilized, another study that had incredible outcomes, both metabolically and in terms of mental health. They actually were able, in that study, to show a dose response effect between the levels of ketones and all types of different outcomes. So the higher the ketones were, the more energy people had, the better mood they had, the lower the anxiety that they had. And really huge reductions in impulsivity correlated with elevating ketones. So that was really cool. That study also had a magnetic resonance spectroscopy component, where they were able to show huge reductions in glutamate on these people on a ketogenic diet, which we know is one of the mechanisms of bipolar disorder, and it’s one of the ways in which these medications work. But their reduction in glutamate on MRS was higher with this ketogenic diet than has ever been measured with any of the anti-convulsive medications that are used in bipolar disorder. So that was also very, very cool.
Chris Kresser: Yeah, that’s remarkable. I can’t say surprising to me, but remarkable nonetheless. So yeah, what’s going on-
Matt Bernstein: And then another one just came out this year with college students, which was cool, too. So this is depression, college students with depression. And one of the complaints sometimes people have this, oh, well, you can’t get people to do this diet. Well, all these studies are proving that’s not true. They were getting people with very serious illness. In this case, they got college kids who are depressed at college to do a ketogenic diet. And again, they weren’t providing the meals. They taught them how to cook and make the food, and these kids made the food, they had incredible results on their depression in the course of a semester. So again, the studies just keep coming out, and the ones that are currently going on, there’s many going on now that are actually randomized controlled trials. So the people who are saying, well, I’m waiting for the randomized controlled trial, well, they’re going to see those in the next couple of years, which is really exciting.
Chris Kresser: Well, I mean, that’s a whole other conversation of whether RCTs fit into a root cause, comprehensive functional medicine type of approach. I mean, that whole system is designed to study medication, essentially.
Matt Bernstein: I agree 100 percent. Yeah, and it’s very hard to do an RCT with a diet, also.
Chris Kresser: Highly problematic.
Matt Bernstein: Yeah, it’s very true. But they’re still doing them, and they’re going to have all kinds of fancy science components with these RCTs that are happening now, functional imaging and metabolomics and proteomics, we’re going to learn a lot more, too, about the mechanisms and the ways in which this approach can provide healing.
Chris Kresser: For sure. I mean, it’s still very useful. And I think over time, we’ll come up with better methods for studying functional interventions. I know Mark Hyman, at the Cleveland Clinic, they were working on this, where they would study, they would compare standard of care to a personalized functional medicine treatment. And that’s not an RCT, but it’s a kind of real world way of measuring, okay, what happens if you go to a conventional doctor and take the medications and do what you would typically do, versus what happens if you go and see a functional medicine clinician and get individualized treatment protocol and then just compare the outcomes there? And I think that could be an interesting model here.
Matt Bernstein: Absolutely.
Chris Kresser: Are there any specific mental illnesses or specific populations for which the ketogenic diet has been shown to be more or less effective? Or is it like a condition that’s like, stand out, really, really effective. Or a population that’s like, ah, for whatever reason, it’s not working well in this population. We don’t understand why.
Matt Bernstein: Well, we don’t have any where we have found that it’s not working. Wherever it’s been studied and there’s case reports and case series in almost every single mental illness at this point. So spanning schizophrenia, schizoaffective disorder, bipolar, major depression, OCD, even eating disorders like binge eating disorder and even anorexia, where there’s the most skepticism in my field, using any restrictive diet in anorexia, but there’s actually some really nice data and a couple of big studies going on right now in anorexia. I’ve seen it be helpful in PTSD, for sure, and even in people with, quote, unquote, personality disorders, which is a whole controversial topic in and of itself, but a lot of that has to do with affective lability, affective instability. Ketogenic diet is really helpful for that, because it really stabilizes neural networks. So we see people just get to a different place, and they almost seem like they have a different, they almost seem like a different person, in some ways, like a different personality, just a better version of who they were before.
So we’ve seen it be effective in almost everything. The most data is definitely in the more severe conditions. So the conditions like bipolar disorder have probably been studied the most, schizophrenia, major depression, this is where we’ve seen the most data. But we’re also in every neuropsychiatric condition, so things like autism spectrum disorders, there’s data, certainly in mild cognitive impairment and early Alzheimer’s, there’s very good data. And even in early alcohol withdrawal, there was a really nice, randomized, controlled trial done at the National Institute of Drug Abuse showing that people needed fewer benzodiazepines to detoxify from alcohol and had much fewer cravings for alcohol. Total big changes on their functional imaging studies that were done during that study as well. So it really does seem like it works in all of these different conditions, which sometimes makes me feel like I’m, like a snake oil salesman or something. It works in this, it works in this, it works in this. But it really does. I mean, and that’s because it’s going at root causes of what goes wrong in the brain. The brain fails when it has energy deficits, and this really fixes all of that by mechanisms that are well studied over the course of decades. Because of the literature in epilepsy, the neuroscientists have been all over this, studying this for many decades now.
Chris Kresser: Well, that’s the key insight there is if you were approaching things from a root cause, then there is such a thing as a panacea in the sense that, because if something is addressing a root cause, then by definition, that root cause affects many downstream pathways. And I think people understand this about gut health, for example. We know now that our gut health affects literally every system of the body. There’s a gut-skin axis, there’s a gut-brain axis, there’s a gut-immune axis, there’s a gut-eye or ocular axis, there’s a gut-gonadal axis. There’s a gut everything axis, because it’s really one of the foundational core aspects of health. So you can say our gut health, if you improve your gut health, everything will improve. And you can say that in a completely evidence-based, research-backed way.
Matt Bernstein: That’s right.
Chris Kresser: Whereas if you’re looking at medications that either suppress or manage symptoms or are basically acting on upstream or downstream pathways like end results, then it’s impossible for a medication like that to have that sort of effect, because it’s working, if you’re to imagine like a tree, it’s working on the far end of the branches, not at the roots of the tree.
Matt Bernstein: That’s right.
The Mechanics of How Ketones Affect the Brain
Chris Kresser: So, I mean, that makes perfect sense to me. So let’s get a good segue into the next question I want to ask, which is, what is going on here with ketones? So, we’ve established that ketogenic diet is effective for lots of different mental health conditions. You alluded to one of the mechanism, or the primary mechanism, perhaps, is related to energy, providing energy to brain cells. So, maybe start with like, what gets broken in mental illness, and how, then, does providing ketones as the primary fuel source to the brain, fix that problem?
Matt Bernstein: Yeah, excellent question. I mean, I think first we want to start off with this idea that the brain is the most energy intensive organ in the body. So it weighs about 2 percent of one’s body weight, and at any one point, is using 20 to 25 percent of total energy resources at any one time. So it’s an energy hog, the brain. It’s where most of our energy goes. So what happens? We know from, again, decades of research, that all of these mental health conditions and other brain health conditions have a component of brain insulin resistance. So I don’t know how, if we want to go into what that means. I’m assuming many in your audience may understand that.
Chris Kresser: Absolutely. They’re geeky.
Matt Bernstein: Yeah, so insulin resistance. Insulin does many things, but one of the main things that it does, it brings glucose in the cells. And when the brain cells, the neuron becomes insulin resistant, it essentially means that even if one just had a big carbohydrate meal and there’s glucose bathing the neuron, it can’t get that glucose in to use as fuel, and so it’s literally starving for energy, and that fuel source that it’s used to is just right outside. It can’t come in because of that insulin resistance. Insulin resistance develops over time because of many factors, but a lot of it has to do with how we eat. And we’ve been told to eat 50 percent or 60 percent of our calories from carbohydrates. And people are eating six times a day, and their insulin is high all day long. And eventually those cells, because they’re seeing insulin all the time, become resistant to that signal, essentially. And so we’re thinking about that, this neuron that’s starving for energy, it can get dysfunctional in any way possible. It can get hyper excitable. It can get hypo excitable. And that can then manifest as any one of these mental or neurological illnesses that we’ve talked about.
Ketones do not need insulin to get into that neuron. So, once someone switches over to a ketogenic diet, those ketones just slip right into the neuron, no need for insulin, and provide this wonderful source of, or an additional source of fuel. The brain never stops using glucose, but now whenever it is running out of energy, that neuron can pull ketones in, have enough energy, and that stabilizes that network, that neural network. So that’s a huge and important component. In addition, because we’re on this ketogenic diet and we’re not eating carbohydrates all the time, we can actually reverse that insulin resistance by being on the ketogenic diet. So we solve the fundamental problem that cause this in the first place, and then we have to talk about mitochondria. So mitochondria are a huge part of this story. Mitochondria, obviously, the energy factories in the cell, but they do way more in all cells, but in neurons, way more than just producing energy. And ketones are a signal to mitochondria to make more of themselves, mitochondrial biogenesis, and to go through mitophagy or recycling of the old, damaged mitochondria. Ketones are our direct signal to cause both of those things to happen. And so we improve the health of those mitochondria, we make more energy, but also mitochondria involved in expression of genes in the nucleus of the cell. They’re involved in the first step of hormone synthesis. They actually huddle around at the end of neurons, and cause the neuron to release those vesicles filled with neurotransmitters. So they’re involved in neurotransmitter communication, and they’re involved in inflammation too. They initiate inflammation, and they help resolve inflammation.
And so when the mitochondria become dysfunctional, which is a hypothesis of what’s going on in all of these mental health conditions, we make them functional again, and we get an actual healing process going on. So this is huge. In addition, we reduce oxidative stress in the brain. We reduce inflammation in the brain, and we change the GABA to glutamate ratio. We talked about glutamate going down in that one study, but we also increased GABA through the ketogenic diet. And finally, ketones actually cause the expression of BDNF, brain derived neurotropic factor. So we can have this wonderful stimulus so these neurons will connect with more neurons and create flexibility in the brain, which essentially is what creates mental health, is the ability for the neurons to be flexible and change when they need to. So all these mechanisms have been studied and elucidated for decades. Even though the metabolic psychiatry field is new, we know these brain health mechanisms from the epilepsy literature. And so we have so much science behind all of this.
Chris Kresser: And even other studies on other conditions, like we know exercise increases BDNF in the brain. It’s one of those primary mechanisms by which it helps and there are issues with BDNF and dementia and Alzheimer’s. And you can leverage this other research that’s already been planned to extrapolate how those mechanisms would produce a benefit. That’s interesting.
Matt Bernstein: That’s right. And of course, exercise is very synergistic with the ketogenic diet and trying to get people. But once people are in ketosis, people who didn’t feel like they could exercise, all of a sudden, now can exercise. And so then we get those synergistic benefits as well.
Chris Kresser: So what sort of results are you seeing in the populations you work with? And everything from like, if you’re working with patients and you start them on a ketogenic diet, or somebody who’s listening to this wants to start a ketogenic diet and they’re on medication, obviously, we want to advise them to speak with their practicing clinician, whoever prescribed the medication. But the reason I’m bringing this up is, I think it’s important for people to know that, if they start doing one thing that improves their mental health, they have to pay attention. The dose of the medication they’re taking may need to change as a result of that.
Matt Bernstein: That’s absolutely right.
Chris Kresser: So please speak to that a little bit.
Matt Bernstein: Absolutely yeah. And of course, people who are taking these types of medications for these types of conditions, many of them already feel that they don’t want to be on these same doses of medications forever. They don’t feel well on them. They feel sedated, they feel slowed down, they feel cognitively dulled. They may have gained 40 or 50 or even 80 pounds since they started taking these medications. They may have developed prediabetes or diabetes and hypertension, and all these things. And I agree with you. People can’t take matters in their own hands and just start lowering their medication. It does need to be done in conjunction with a medical professional. That being said, let’s talk about what’s possible, which is very, very exciting.
So people often come into the program that I run called Accord, and they’re on way, really high doses of multiple psychiatric medications. Often people come in on four, five, six medications at a time, doses where they often can’t stay awake and yet they still have symptoms. The whole point of these medications, we think, is to lower symptoms. But what’s going on out in the field is that people are just adding more and more medication, even though the symptoms aren’t getting better. So we’ll start them on a well formulated ketogenic diet. We have a dietitian, local who’s right in the program, who formulates it for us, often, usually using a 1.5 to one ratio to start. Sometimes we’ll go up to a two to one ratio. We’re trying to target ketone levels around 1.5 or two or higher, depending on the condition. People are often able to get to there by the second week, maybe the third week, if they’re not exercising. We try to get people exercising, doing some mindfulness practices, which is also a very important part of all this. We can talk about mindfulness and mitochondria a little bit later, if you want.
And then circadian rhythm alignment as well is very important. So getting up in the morning, seeing sunlight, getting outside multiple times a day, to be in the sun, and then blocking blue light at night and getting to bed at a reasonable hour, which is also something that people generally aren’t doing before they come. And we can start lowering medication often in the first month. And I have seen the ability to get off of one, two, three, four medications over time. Eventually, even some people getting off all of those medications. It can take quite a while. It needs to be done carefully and slowly with a professional who understands how to taper medications, because all of these psychiatric medications do have withdrawal effects. We think about withdrawal effects with SSRIs, but all of them, the mood stabilizers, antipsychotics, they all have withdrawal side effects, which means we have to go slowly and carefully, but we can steadily keep reducing these medications. People’s symptoms go down, their energy goes up, their mood goes up, and people say, I can think again. I feel like myself again. I can’t tell you now how many people have come and said, this is the most important thing that’s happened to me in the last 25 years, is doing this treatment program, because I felt like I wasn’t living life for that entire period of time, and now I’m like, I can live again. And sometimes that response doesn’t take that long. I mean, we can sometimes get that kind of perspective after two months. It’s amazing how powerful it is.
Considerations for Treating Kids and Teens
Chris Kresser: That is pretty incredible. We talked earlier about populations. I’m curious about kids and obviously there’s a lot of research on ketogenic diet being incredibly effective in the context of refractive epilepsy, for example. Kids who are, and the medications for that can be brutal, the side effects can just be so rough. And even young kids are able to do this. So I’m not sure if you work with kids in your practice. I mean, obviously you have your own kids and their story. What’s your experience been like with kids and teenagers, for example? Of course, there are particular considerations with kids who are still growing and how the diet may need to be modified for them. But I know a lot of parents listen to this podcast, and they’re going to be curious about whether this is applicable for their kids and teenagers.
Matt Bernstein: Absolutely. Yeah, it’s a great question. I don’t generally treat kids, but I do know the literature about this. And so we have this wealth of information about treating kids with ketogenic diets from the epilepsy world. And one important point to make in the epilepsy literature is that not only when these kids go on the ketogenic diet, can they come off all of those medications and retain seizure control. Many of them only need to be on the diet for two or three years, and then they can come off of it and retain all of those benefits. So it’s literally, a permanent healing of the brain for kids. So childhood is really the best time to undertake this, because the brain is still developing and growing. It’s still very plastic. We haven’t developed all these problematic networks that can develop eventually in late teens and 20s. So this is a wonderful time to think about this kind of approach. And often the mental health conditions are not quite as far along as what I’m describing. I’m talking about, full blown psychosis and mania and depressive episodes, with suicidal ideation. With teens and kids often we’re talking about, usually the first symptoms being attentional issues and anxiety that start developing. And that’s a wonderful time to think about using this kind of approach, because we wouldn’t even necessarily need to achieve high levels of ketosis to treat those types of conditions.
It could be a fairly low ratio of the diet. The hardest part is actually convincing a teenager to do this kind of thing. But if you can, if parents can catch their kid before they get into that willful teenage, those willful teenage, adolescent years, they may be able to get them on the right path early on, and get them feeling better, and then hopefully that young child, turning teenager, understands how important this is, that this is the way they were feeling before, and this is how much better they’re feeling now. And really make that connection that the diet and the exercise and the mindfulness practices are the things that created this great feeling and great life for themselves.
Chris Kresser: Yeah, the middle school and teenage years are definitely the hardest, because before that, the parents have quite a bit of control over what kids are eating. And then by college, I think most young people are generally a little more able to make the connection between their behavior and how they feel, and they’re able to behave in a more rational way, shall we say. But teenagers and even late middle schoolers are not known for their rational behavior.
Matt Bernstein: It’s so true.
Chris Kresser: And there’s a lot of differentiation happening, and all this stuff that kind of works against them making good choices in this regard.
Matt Bernstein: It’s true. And it’s also, they’re going against the culture of their friends and what everyone else is eating and it’s, I’m not saying that it would be easy. It’s tough, but there is actually a really interesting study that I want to tell anyone in the audience who’s a parent, about. They looked at this longitudinal study. It was more than 10,000 kids. Studied them from childhood all the way into their early 20s. They were measuring metabolic parameters throughout that whole time, and then eventually measuring mental health outcomes in their 20s. And the results were really incredible. So the kids who had the highest insulin levels compared to the lowest insulin levels at age nine, more insulin at age nine led to a three-fold increased risk of schizophrenia in their 20s. So just having the elevated insulin from diet, and then the kids who gained the most weight in puberty had a five-fold increased risk of major depressive disorder in their 20s. And so that’s how important this is, metabolic health in childhood eventually leads to severe mental health risk in early 20s. And so there’s a lot at stake. So yes, it’s hard, but it’s also incredibly important.
Chris Kresser: Yeah, that’s pretty important information for parents to know, especially going back to what you said earlier. We’re not talking about disease management necessarily here. If you intervene early enough, you’re actually talking about a root cause resolution, where you lead to changes in the brain that become permanent, because they happen at a time, at a development, during a developmental period where those things are becoming hardwired, or at least soft wired. And we know that the brain is quite plastic, and lots of changes can happen over time. But I think we can, even the recent research on neuroplasticity would suggest that doing those changes earlier is easier, while the brain is more highly plastic than it is later, when you already have those deeper grooves embedded in the brain, if you will.
Matt Bernstein: I agree 100 percent. Yeah, that’s right.
Chris Kresser: So a little bit of, it is a huge effort, especially for kids. But I mean the fact, the college student study that you pointed to earlier shows that it is possible. And I think that even with teenagers, I happen to have a teenager myself, so once they figure out that the change that they’re making is connected to an outcome that they care about, I think that’s the key to supporting teenagers with that kind of behavior change. It’s like, so you really want this, could be clear skin, for example, something teenagers care a lot about. A ketogenic diet, if they also have mental health problems, they may be less motivated to try to fix that problem. They may be more motivated to fix the skin problem.
Matt Bernstein: That’s right, whatever motivates someone. That’s right, whatever motivates someone. Yeah, I often say, my goal as a psychiatrist is to help people’s brain health and their mental health.Their main motivation sometimes to do this intervention is to lose the 50 pounds that they gained on the medication that they were taking. Doesn’t matter what the motivation is. We can meet in the middle and agree on the plan, and we both, we’re all happy. And then in the end, they’ll often come back and say, I didn’t believe you about the mental health part, but you were right. That’s actually really, really significant too. I was doing it for weight loss, but actually I feel so much better. I have all this energy, my moods better, my anxiety is better, my attention is better. All of it.
Chris Kresser: Yeah, we’ll make the weight loss easier to maintain, as you talked about earlier.
Matt Bernstein: Exactly.
Therapeutic Targets for Ketone Levels
Chris Kresser: Let’s finish by talking a little about some specifics. There certainly is a spectrum of ketosis, and how much, how many ketones are produced, and there are different methods for getting into ketosis. And there’s different approaches to ketosis, like within, for example, that you might do with recalcitrant epilepsy, you have to really be in deep ketosis in a lot of cases to get the benefit. Whereas with weight loss, for example, you may not need to be in that, at that level of ketosis to get a benefit. So where do you, what do you target in terms of ketone production and the sort of level of ketosis for mental health outcomes?
Matt Bernstein: Yeah, well, and of course, we’re measuring beta hydroxybutyrate, which is one of the main ketones. The best way to measure that is with a little meter that measures a little drop of blood. So it’s similar to what a diabetic would use to prick their finger and put it in the meter. And we think about therapeutic ketosis starting at about point five. For things like mild to moderate depression, anxiety, maybe some mild to moderate ADHD, I would target around point five to one as being adequate for most people with those types of conditions. For people who have a more severe depression, for people with bipolar disorder, schizophrenia, like I said, we’re targeting more like 1.5 or two at least on their beta hydroxybutyrate. But the caveat that I would say is that beta hydroxybutyrate fluctuates throughout the day quite a bit, and so we’re only getting this one snapshot. And so we have to be careful not to make too much of the numbers, because they’re going to change quite a bit. We know this because now some people have access to these continuous ketone monitors, which are really cool, which, unfortunately, are not approved in the US yet. But I had someone who got his hands on one and over the two weeks, it was remarkable. His curves were early morning, his ketones were only about .6, .7. Later in the day, they were up to two in the evening. By the middle of the night, they were all the way up to four. And so it really depends on when one’s measuring them. They’re very dynamic. We’re making ketones all the time, but then we’re using them all the time. And so it really changes with the circadian rhythm as well. And probably, connected to all the other hormones that we’re thinking about.
So, suffice it to say you have to have a little bit of experience in figuring out exactly what these ketones mean, these ketone numbers mean, but we definitely need to target a little higher for the more severe conditions. And generally, if people want to measure the same time every day, probably the evening is the best time to measure to get a nice sense of where one’s ketones are. If you really wanted to do a good experiment, you can, maybe for a week, measure them maybe three times a day, and really get a sense of how they’re changing throughout the day as well.
Chris Kresser: What about ketogenic supplements or compounds like MCT or Leucine is a ketogenic amino acid, or exogenous ketones? Have you played around with those much as a way of helping people to get into ketosis? Or to generate ketones?
Matt Bernstein: Absolutely. Yeah, we use MCT a lot, and that’s also something from the epilepsy world. The MCT version of the ketogenic diet is very popular because it allows one to eat a more standard looking kind of plate of food, but still achieve higher levels of ketones, because you can supplement with this very ketogenic fat, the medium chain triglyceride oil. And I like that one, because it’s still our body naturally turning a food into ketones. And so, our body, our liver still now has control over how it’s going to do that, to some extent. As opposed to exogenous ketones, which are really, you’re just artificially, essentially putting this external ketone into your body. And the problem with exogenous ketones, too is that they’re very short acting generally. They’re now making formulations that last a little bit longer, but still only about three hours or so. And so we get the signal of ketones, but we don’t get the fundamental metabolic change that we would get by doing the ketogenic diet, which is having low insulin all the time, reversing insulin resistance, and all of those things that are happening with a ketogenic diet.
So, I think exogenous ketones are helpful for sort of performance enhancement, sometimes. They may be helpful sometimes for someone just to know what it feels like to be in ketosis. If someone wants to just say, I’d like to see what this feels like. But the hope would be then to transition into a different diet, and maybe including some MCT to boost the ketone levels. I haven’t played around with leucine in particular, but I do really advocate people eating animal protein as their protein source when you’re doing a ketogenic diet. We talked a little bit about growth in kids. One of the things people do need to know is that ketogenic diet is high fat, moderate protein, low carbohydrate, which means that you can’t just eat protein all day and be in ketosis. Protein essentially causes an insulin response, and the insulin will be too high if you’re eating protein, huge amounts of protein all day. And so we keep it more like around 1.2 grams per kilogram of body weight, unless someone’s exercising a lot, in which case, then they could do maybe 1.6 grams per kilogram of body weight and still get into deep ketosis. But unless someone’s exercising a lot, it’s more like 1.2 grams per kilogram of protein a day.
Chris Kresser: That’s one of the areas where I found leucine to be helpful. Is if you add leucine to, let’s say, five grams of leucine, I found that you can boost protein intake a little bit without affecting ketosis. I mean, we’re not talking about doubling, but certainly boosting. I’ll send you a study on this that was pretty interesting from back in 2018. That was one of the main things that they were looking at is like, I think it’s particularly like in the epilepsy literature. Especially with kids, you don’t want to have, they were often having to really, really restrict protein intake in order to get them into that deep of a level of ketosis, which, of course, is a little bit problematic for the kid who’s still growing and needs that protein for tissue scaffolding and muscle development, etc. So leucine is one of the ways that you can kind of mitigate that and add a little more protein.
And then more recently, I’ve been looking at butyrate. There’s some interesting research showing that butyrate is as ketogenic, or more ketogenic than leucine, and now you can supplement with bioavailable forms of butyrate that are better than sodium butyrate and actually reach the colon intact.
Can mental illness be a metabolic problem? Learn how ketogenic therapy is transforming treatment for depression, bipolar disorder, and more in this episode of Revolution Health Radio #ChrisKresser #RHR #MentalHealth
Matt Bernstein: Oh, amazing.
Chris Kresser: Yeah. So that’s kind of interesting, too. So I’ve been playing with adding butyrate and leucine to the ketogenic diet just to support ketosis. And they work like you were saying, more like MCT or something that’s promoting endogenous ketone production, rather than just using exogenous ketones, which I think is better long term.
Using Ketogenic Diets to Address Behavioral Disorders
So last question for you. We haven’t talked that much about behavioral disorders. You briefly mentioned ADHD, but there’s a growing number of kids who have autism spectrum, are on the autism spectrum, Asperger’s, OCD, oppositional defiance disorder, like a lot of newer diagnoses that are maybe not classically considered mental illness, but exist on a spectrum of behavioral disorders. Are you familiar with the research on ketogenic diets and those conditions?
Matt Bernstein: Yeah, yeah. I mean, there’s some really nice work on autism and ketones that it looks very effective in all the studies that have been done. They haven’t done big studies yet on that, but it’s certainly something that I would strongly consider if I was a parent in that situation. No matter what form of autism, whether it be the more high functioning or the more profound forms, I would absolutely consider it if you can make it happen. And certainly in ADHD, I see this as being almost like a magic bullet. I mean, if you could get a kid with ADHD into ketosis, everything is going to get better. Everything is going to get better. And it’s such a more holistic and root cause intervention than using stimulants. I’ve seen many cases of OCD get better, and there’s wonderful case reports about it as well, out in the literature. So I definitely see OCD as one of the conditions where this is a great intervention as well.
When we get into things like oppositional defiant disorder or intermittent explosive disorder, these are things that are very complicated. And I don’t know if I can speak to those. I haven’t seen any work on ketogenic diets and those. But, the way I see it again, it’s like we’re fixing neural networks. There’s no reason in the world that if you could try to make this happen, that it wouldn’t make sense to try this. Because what do you have to lose in a situation like that? I mean, you’re already in a real pickle when you’re getting a diagnosis of oppositional defiant disorder in your kid, you’ve been through a lot at that point, and most things probably haven’t worked that you’ve tried. This is something that ought to be tried, I think, in a situation like that.
Chris Kresser: Right, and going back to what we talked about earlier, like in conventional medicine, you have a different doctor and a different treatment for every part of the body, because they’re not seen as being related. But every disorder challenge, whatever you want to call it, that we just talked about, is mediated by the brain, right?
Matt Bernstein: Absolutely.
Chris Kresser: So if you’re doing something that fundamentally improves the mitochondrial function of the brain and the brain’s ability to utilize energy, then it’s hard to see how that wouldn’t provide some benefit in virtually any mental health or behavioral condition. Now, of course, as you said, it doesn’t mean it’s going to cure it 100 percent, it doesn’t mean that other things won’t be necessary. We don’t want to be too reductionist here and just say that everything is 100 percent biochemical. There are obviously still behavioral considerations, environmental factors, and by environment, I mean the larger exposome, not just environmental toxins, but just relationships, familial contacts, socioeconomic factors, etc. We’re not trying to explain those away and just say that we can wave a magic wand and improve brain energy metabolism and fix all mental health problems. That’s ridiculous. But we are, I think, in agreement here that this is a fundamental root cause of mental illness and behavioral disorders that can be relatively, affordably, and accessibly addressed with this. We’re not talking about drugs that cost $3,000 a month. We’re not talking about having to see a specialist that you have to wait six months to see. We’re not talking about crazy expense. We’re talking about something that most people can integrate into their lives.
Matt Bernstein: That’s right, yeah. It doesn’t have to be expensive. That’s another sometimes complaint people have. Oh, well, that’s so expensive to eat that way. Not necessarily just get the macros right with real whole foods. People have studied this, actually, in the diabetes population using ketogenic diet in people on Medicaid and food stamps, and they’re all able to do it. They just get some ground beef and some veggies and some cheese, and it’s all, and eggs, and it’s inexpensive, and they eat a whole foods version of a ketogenic diet, and they reverse their diabetes. We haven’t even talked about how powerful the ketogenic diet is for diabetes.
Chris Kresser: Fortunately, I have talked about that in several episodes in the past.
Matt Bernstein: Oh good.
Chris Kresser: So people have definitely heard about that. Yeah. It really, yeah.
Matt Bernstein: And the one final thing I would say is that people just need to be a little patient when they’re doing this too. I mean, I don’t want people to think that the moment you go into ketosis, the skies part and everything is different, and the birds are chirping and, nope, all the problems melt away. It doesn’t work like that. I mean, these networks took a long time to get dysfunctional. We get into ketosis, and we start often seeing some benefits right off the bat, but the full benefits come many, many months later. And so each like, month two is better than month one, month three is better than month two. And it keeps getting better as you go into more and more months. And I would say year two is better than year one, if someone continues to do this. And so the healing just keeps happening. And so these, when people hear about these, sort of miraculous cases of people with 50 years of schizophrenia, coming off all their medications and never having another auditory hallucination again, that didn’t happen in month one. It happened over the course of the whole first year or two. And so that’s also a really important point, is that it does require a little bit of patience and long-term thinking to do this.
Chris Kresser: 100 percent. And it’s also just, like you said, an adjustment process where with keto some people actually can feel worse in the first few days, that there’s, the keto flu is real.
Matt Bernstein: It is, although you can largely avoid it with enough fluids and electrolytes. We generally don’t see it.
Chris Kresser: Yeah, electrolytes, especially. This is where LMNT even started in the first place, right?
Matt Bernstein: Yes, that’s right, that’s right.
Chris Kresser: It was to address this problem.
Matt Bernstein: But even beyond keto flu, there’s keto adaptation. And so, your cells don’t know quite what to do with this new source of fuel sometimes for a few weeks, and they don’t really know everything to do with it, and mitochondria really don’t understand what they’re doing yet, sometimes for a few months. And so that’s that adaptation process. So yeah, so it takes a while to fully get the benefits, but it’s really worth it.
Chris Kresser: Great. Well, fantastic. Really enjoyed this. Where can people find out more about your work, Matt?
Matt Bernstein: So one good place to go is the website for this program I’ve been describing, Accord. And it’s Accordmh.com. People can see what we do. There’s lots of, tons of information in there, including an academic lecture, a video of an academic lecture that I gave, if people want to dive in more deeply in the science.
Chris Kresser: Let me just touch on this. So this is a residential program, right?
Matt Bernstein: It is, yes.
Chris Kresser: So people come-
Matt Bernstein: It’s a residential program. People come and live with us, or they can stay nearby and just come during the day and just get all the programming, but stay in their own place nearby. We’re right outside of Boston in Massachusetts.
Chris Kresser: And how long is the program, typically for the resident?
Matt Bernstein: So it’s four weeks minimum, and some people stay eight weeks or 12 weeks, depending on their condition. It’s not only all the treatment and we do lots of measurements, but also people are learning the whole time. It’s all about learning how to sustain this when they get home. And we even have all types of education for the families as well, so that they know how to help their family member, support their family member, when they get home. So yeah, so that’s one place to find me. And then the other place, I’m not on a lot of social media, but I am on LinkedIn. So if anyone wanted to reach out to me individually, they could find me on LinkedIn and reach out. And I always would respond to someone who’s got any questions or just wants to discuss anything.
Chris Kresser: Fantastic. Well, thank you so much, Matt. It’s been a pleasure. I really have enjoyed the conversation. I know the listeners will as well. And I wish you, thanks for doing this work. It’s great to know, I wasn’t familiar with the Accord program, so it’d be great to be able to refer people to that when they need it.
Matt Bernstein: Thanks so much for having me. It’s really fun.
Chris Kresser: Pleasure. Okay, thanks everyone for listening. Keep sending your questions to ChrisKresser.com/podcastquestion. We’ll talk to you next time.
