The Science of Metabolic Psychiatry: How Ketones Feed a Starving Brain | Dr. Matt Bernstein

Show Notes

Here is a claim that sounds almost too big to believe: in a small pilot trial at Stanford, every patient with schizophrenia or bipolar disorder who stayed fully adherent to a ketogenic diet went into remission. Not improved. Remission.

Dr. Matt Bernstein is quick to qualify what that does and does not mean, and he does it repeatedly through this conversation. But the idea underneath it, that severe mental illness is in part a brain energy problem, is one mainstream psychiatry has barely begun to reckon with.

Bernstein is a traditionally trained psychiatrist. He spent years on inpatient units treating psychosis, severe mania, and catatonia with medications and ECT. Around 2010 he moved into psychosocial rehabilitation and came to believe that medications, while they stabilize people in the short term, can sometimes get in the way of long-term functional recovery. He now runs Accord, an immersive metabolic psychiatry program outside of Boston, where a chef, a dietitian, a personal trainer, and a social worker help patients use diet and lifestyle to treat serious mental illness.

His path into this field started close to home. Around 2017, two of his three sons developed sudden, severe OCD, depression, and cognitive symptoms that turned out to be a form of autoimmune encephalitis. Not long after, he sat in a grand rounds lecture by Dr. Chris Palmer at McLean Hospital, a colleague he knew from residency, and says he may have been the only person in a room of about 150 who walked out fully convinced. He put himself on a ketogenic diet before he ever prescribed one, and in retrospect believes he had been insulin resistant himself. That personal experiment became the seed of Accord.

The biology centers on brain regions that depend on insulin to pull in fuel: the hypothalamus, the hippocampus, and the amygdala. Most of the brain takes up glucose without needing an insulin signal, but those regions do not, and when they turn insulin resistant the neurons that govern mood, memory, and anxiety start starving even while glucose is plentiful everywhere else. Ketones sidestep the problem completely. They diffuse into cells without any insulin signal at all, which is why Bernstein describes the switch into ketosis as an immediate rescue for exactly the regions that are running on empty.

The evidence is early and Ravi presses on that. The Stanford pilot led by Dr. Shivani Sethi was single-arm, with no control group. A 2022 French inpatient series of about 31 patients found effect sizes above 3 on standard psychiatric scales, compared to roughly 0.35 for SSRIs and 0.5 to 0.6 for antipsychotics against placebo, but it too had no control arm. Randomized trials at UCSF and in the UK are underway. What Bernstein offers in the meantime is a clinician’s honesty: he tells patients they need about three months in ketosis before they can really know if it is working, and says he has yet to see someone reach that mark and feel nothing.

They also get into the practical layer, which is where most people actually get stuck. Ketogenic ratios and why Bernstein starts most patients at 1:1 rather than the 4:1 of the original 1921 epilepsy diet. Why he keeps protein high when the classic epilepsy version keeps it low. Why a single fingerstick ketone reading can mislead you. Why a phone call can spike a patient’s blood sugar to 140 on a continuous glucose monitor with no food involved. And why the diet is only one lever in a package that includes exercise, sleep, sunlight, and connection.

Episode Resources

• Accord, Dr. Bernstein’s clinic
• Dr. Bernstein on LinkedIn
• Dr. Ravi Kumar’s Website
• Dr. Ravi Kumar on LinkedIn
• The Dr Kumar Discovery on YouTube
• The Dr Kumar Discovery on Apple Podcasts
• The Dr Kumar Discovery on Spotify
• The Dr Kumar Discovery on Instagram

In this episode, you will discover:

• Parts of your brain need insulin to eat: The hypothalamus, hippocampus, and amygdala rely on insulin to pull glucose into their cells, so when those regions turn insulin resistant, the neurons literally start running out of fuel
• Ketones bypass the gate: They diffuse straight into cells without an insulin signal, delivering what Bernstein calls an immediate rescue to exactly the regions that govern mood, memory, anxiety, and psychosis
• The Stanford pilot: In a small single-arm study led by Dr. Shivani Sethi, every patient with schizophrenia or bipolar disorder who stayed fully adherent to the ketogenic diet reached remission, alongside reversed metabolic syndrome markers
• The effect sizes are unusual: A 2022 French inpatient series of about 31 patients found effect sizes above 3 on standard psychiatric scales, against roughly 0.35 for SSRIs and 0.5 to 0.6 for antipsychotics compared to placebo
• Both studies had no control group: Bernstein says so himself, and randomized trials at UCSF and in the UK are the ones that will settle it
• Three months is the honest timeline: Bernstein tells patients they need to stay in ketosis roughly that long before they can know if it is working, and says he has yet to see someone reach that mark and feel nothing
• Mitochondrial biogenesis may matter more than the fuel switch: Ketones activate a pathway called PGC-1 alpha that drives the growth of new mitochondria, which may be why some patients keep improving well past the one year mark
• Ketones turn on the BDNF gene: The result is a more flexible, adaptable brain, which Bernstein calls the actual definition of mental health
• Ratios are not what most people think: A ketogenic ratio is grams of fat to grams of protein and carbohydrate combined, and while the 1921 epilepsy diet used 4:1, Bernstein usually starts patients at 1:1
• He keeps protein high on purpose: Unlike the classic epilepsy version of the diet, protein stays up, because signals released from working muscle act as a growth signal the brain can pick up on
• One ketone reading can fool you: Beta-hydroxybutyrate can swing tenfold across a single day, so Bernstein cares far more about how a patient is doing than about one afternoon fingerstick
• Stress alone spikes blood sugar: On a continuous glucose monitor, one patient went from a flat 60 to 90 line up to 140 purely from a panic-inducing phone call, and came back down within five minutes of slow breathing
• Cost is not the barrier people assume: Studies suggest a whole-foods ketogenic diet built around things like ground beef, cheese, and onions can be done on food stamps

Key Takeaways

The brain is an organ, and it runs on energy. Psychiatry has spent decades treating mood and psychosis as purely a chemistry problem, disconnected from the rest of the body. The metabolic view does not throw that out. It adds a layer underneath it: if the cells cannot get fuel, no amount of neurotransmitter tuning fixes the underlying shortage.

Insulin resistance in the brain is not the same as insulin resistance everywhere else. A person can look metabolically fine on standard labs while specific insulin-dependent regions are starving. That is part of why this gets missed, and why Bernstein says almost no one had ever checked his own insulin.

The evidence is striking and early at the same time. Remission in every adherent patient is a remarkable result, and a single-arm pilot cannot tell you what would have happened without the diet. Hold both facts at once. The randomized trials are running now.

Three months is the commitment. Not three days, not two weeks. Bernstein is direct that the trial period is long enough to be a real decision, and that people who quit early never find out what would have happened.

This is not a diet in isolation. Exercise, sleep, sunlight, connection, and medical supervision are part of the package at Accord, and the diet does not carry the result on its own. Anyone selling keto as a standalone psychiatric cure is overselling it.

Medication decisions belong with your psychiatrist. Bernstein is a physician who spent years prescribing, and nothing in this conversation is an argument to stop a medication on your own. Ketosis can shift lithium levels and electrolytes, which is exactly the kind of thing that requires supervision.

Cost is a smaller obstacle than people assume. A whole-foods ketogenic diet built on inexpensive staples has been studied in people on food stamps. The barrier is usually structure and support, not the grocery bill.

Transcript

[00:00:00 –> 00:00:11] Dr. Ravi Kumar: Welcome back to The Dr Kumar Discovery. My name’s Dr. Ravi Kumar. On today’s episode, I’m sitting down with Dr. Matt Bernstein, who’s an expert in a field most people have never heard of.

[00:00:11 –> 00:00:43] Dr. Ravi Kumar: It’s called metabolic psychiatry. Now when most of us hear the word psychiatry, our minds go straight to a diagnosis, a therapy session, maybe a prescription for an antidepressant or a mood stabilizer. Some people think of it as purely about brain chemistry, like serotonin and dopamine, and completely disconnected from everything else that’s going on in your body. But that type of thinking is insular and incomplete. You see, your brain is an organ just like your heart or your liver, and it runs on energy.

[00:00:43 –> 00:01:34] Dr. Ravi Kumar: And if that energy supply breaks down, whether from insulin resistance, inflammation, or damaged mitochondria, the brain stops functioning in the way that it should. And what Dr. Bernstein has found is that in the most severe psychiatric cases out there, fixing that energy problem can do things medications alone never could. So in this episode, you’re gonna understand what metabolic psychiatry actually is, why a diet invented a hundred years ago to treat children with seizures is now being used to put severe mental illness into remission, what the actual peer reviewed research actually shows on this, and what you can do starting today if you or someone you love is struggling with mental illness. It’s gonna be a great episode. But before we get into it, I wanna give you a quick disclaimer.

[00:01:34 –> 00:01:55] Dr. Ravi Kumar: Dr. Bernstein and I are doctors, but we’re not your doctors. This show is for informational purposes only. Everything you learn from my conversation with Dr. Bernstein is meant to empower you with knowledge. So take this knowledge, ask better questions, and work with your own doctor to build a more informed, healthier life. That’s exactly what I want for you.

[00:01:56 –> 00:02:19] Dr. Ravi Kumar: And just to be clear, the show is separate from my role as assistant professor at UNC. And lastly, more than 100,000 people tune in to The Dr Kumar Discovery every month. The show is growing very quickly, and I’m so appreciative of all your support. But many of you are not subscribed. So if you have the time, please subscribe on whatever platform you’re listening on and leave a review if you can.

[00:02:19 –> 00:02:35] Dr. Ravi Kumar: That makes a huge difference in how the algorithms find us and distribute us. Alright. Let’s get into it. My name is Dr. Ravi Kumar. I’m a neurosurgeon in search of the causes of human illness and the solutions that help us heal and thrive.

[00:02:36 –> 00:02:59] Dr. Ravi Kumar: I want you to join me on a journey of discovery as I turn over every stone in search of the roots of disease and the mysteries of our resilience. The human body is a mysterious and miraculous machine with an amazing ability to self heal. Let us question everything and discover our true potentials. Welcome to The Dr Kumar Discovery.

[00:03:02 –> 00:03:26] Dr. Ravi Kumar: Dr. Bernstein, thanks so much for joining us on The Dr Kumar Discovery. I’m super excited to talk to you like most of my guests because you do something that’s very unique, and it’s metabolic psychiatry, which I think most of my audience members have never heard of. But it’s a practice that I think sounds very relevant and very unique and very creative. Can you kinda tell us what metabolic psychiatry is?

[00:03:27 –> 00:03:39] Dr. Matt Bernstein: Yeah. I’d be happy to. First of all, you know, you can call me Matt. I’m very informal. And it’s a pleasure to be here and, you know, be able to talk with you and and and be introduced to your audience.

[00:03:39 –> 00:04:08] Dr. Matt Bernstein: Yeah. Metabolic psychiatry is pretty new, so I think a lot of people haven’t heard about it. But it’s really this idea that brain health and mental health especially is highly correlated to what’s going on metabolically in the rest of the body. And that people with a certain propensity towards a mental health issue will have metabolic changes in their brain that go on sometimes many years before they present with their first mental health symptom. And we can see that in some of the epidemiology.

[00:04:08 –> 00:04:43] Dr. Matt Bernstein: And so we’re using metabolic levers, which happen to be, you know, lifestyle things. So they’re really safe and have a lot of evidence behind them. We and we combine them all together in this package that can really improve someone’s overall metabolic health in general, but especially the metabolic health of their brain. And we can see these dramatic results in their mental health, even for people with really severe mental health problems, which has been my specialty in my practice, you know, since I started. And it’s still the people that I’m trying to target my treatments towards.

[00:04:43 –> 00:05:06] Dr. Matt Bernstein: And it’s astounding that we can actually think of a diet that might work better for treatment resistant schizophrenia than the most powerful medications, but that’s exactly what happens some of the time. So it’s just incredible to think that that that’s true and and to me, really exciting because we have this new and very powerful tool that’s really safe.

[00:05:07 –> 00:05:17] Dr. Ravi Kumar: Yeah. No. I mean, it’s totally extraordinary, and it makes sense. Right? I mean, the brain uses 20% of all our energy in our body, and it’s this little three pound organ right here.

[00:05:17 –> 00:05:50] Dr. Ravi Kumar: Right. And metabolic sickness or metabolic dysfunction, which affects the whole body, including the brain, is a problem with energy utilization. So if you’re choking off energy to your brain because of metabolic syndrome or metabolic, dysfunction, it makes sense that things would start to go wrong. And when things go wrong in the brain, you know, it’s not like you you have a muscle or a bone that doesn’t work. It’s it’s all the functions that make us who we are, help us move through the world, help us interpret the world, help us plan actions in this world.

[00:05:50 –> 00:06:02] Dr. Ravi Kumar: It’s it’s basically our personalities. And so it just makes so much sense. But I’m curious, how did you get into this? Because, you know, you and I both went to medical school. You know, that’s that’s not what we’re taught.

[00:06:02 –> 00:06:17] Dr. Ravi Kumar: We maybe got, you know, thirty minutes of nutrition lessons in in medical school, and then we go to residency, and they teach us what drugs to prescribe and what procedures to do. So, I mean, how did you end up in this field of metabolic psychiatry, which most people have never heard of?

[00:06:18 –> 00:07:04] Dr. Matt Bernstein: Yeah. Yeah. It’s an excellent question, and and it’s a bit of a personal story, but I’m I’m happy to tell it. So, you know, I was traditionally trained and was practicing in an inpatient setting for many years, treating people with these more severe illnesses, using all the medications and ECT and and everything that was needed sometimes to treat people who are really in in the most acute presentations, you know, psychosis and severe mania and catatonia, things like that. And, you know, I left there that inpatient’s job in around 2010, 2011, and started working for a company that does more psychosocial rehabilitation and really started to appreciate that sometimes the medications, even though they would stabilize people, would actually impair their overall functional recovery.

[00:07:04 –> 00:07:34] Dr. Matt Bernstein: And I think that’s really solid at this point, that there there’s some good literature that that shows that, especially when you follow people for longer periods of time. If you do short term studies, symptoms are better on medication. But if you do long term studies, careful, usually engineered reductions of antipsychotic medication lead to better long term outcomes. But it’s important that the doctor and the and the patient work together on those reductions. If you just do do research protocols where you’d have standard reductions, you know, you don’t get as good of a result.

[00:07:34 –> 00:08:06] Dr. Matt Bernstein: And then I had the personal issue, which is that in around 2017, we have three boys, and two of them, you know, started off being you know, they were all very healthy, but two of them developed an acute onset of very severe, what looked like a psychiatric presentation, kind of almost overnight. And it was very severe OCD and depression, and we were, you know you know, starting to see really good psychiatrists and psychologists. You know, we were well connected based on my job. My wife’s a psychologist as well. And they were getting no benefit from psychiatric treatment.

[00:08:06 –> 00:08:30] Dr. Matt Bernstein: And in fact, know, it was hard for me to admit at the time, but in retrospect and even eventually then, I realized that the medications were not only not helping, but making them worse. Yeah. And then we started realizing that there were a lot of physical symptoms too. It wasn’t just the OCD and depression. They were having really severe cognitive symptoms to the point where, you know, these were straight a, you know, students, and they couldn’t read.

[00:08:30 –> 00:08:43] Dr. Matt Bernstein: And they couldn’t their handwriting changed. They were having all kinds of other symptoms. So suffice it to say, we eventually, we figured out that this was a form of autoimmune encephalitis. Their immune system was attacking their brain. They had elevated antibodies.

[00:08:44 –> 00:09:26] Dr. Matt Bernstein: They had elevated markers of some other infections. The standard approaches even for that autoimmune encephalitis weren’t helping them, and eventually ended up in this whole other world of environmental functional medicine, really doing very different kinds of protocols than you might get from, you know, traditionally trained doctors. And that’s really what moved the needle for them, this huge package of things. And it’s really hard to say exactly what helped when you’re doing so many things all at the same time, but it really did require all of that. And really what it highlighted for me was that my field, psychiatry, just does not honor the connection between the body and the brain in the way that it should.

[00:09:26 –> 00:09:49] Dr. Matt Bernstein: And that Right. The brain is being affected by metabolism as we’ve already mentioned, but it’s also being affected by the immune system and by infections and by what’s going on in the endocrine system. And we just don’t think enough about that in psychiatry. We just, you know, make a diagnosis based on someone’s report. We may do some very cursory screening labs about medical conditions.

[00:09:50 –> 00:10:11] Dr. Matt Bernstein: But as you probably know and as your listeners probably know, that’s often very rudimentary. We’re just getting like a basic chemistry panel and a CBC. And maybe the more extensive version, we might look at, you know, inflammation marker or ceruloplasmin and and copper. But, like, we’re not really looking deeply as to what’s going on in the body. Right.

[00:10:12 –> 00:10:15] Dr. Ravi Kumar: That was PANS or PANDAS that your your sons had?

[00:10:15 –> 00:10:36] Dr. Matt Bernstein: I mean, technically, they call it PANS because PANDAS is specifically from strep infection, and the treatments for strep infection didn’t really help them. Eventually, you know, a big cocktail of different treatments helped them. Okay. So PANS is a more general term for just an acute neuropsychiatric syndrome based on some kind of autoimmune process.

[00:10:36 –> 00:10:37] Dr. Ravi Kumar: Right.

[00:10:38 –> 00:11:04] Dr. Matt Bernstein: Or or and and toxicology process, a toxin process that’s going on in in a kid. Okay. Yeah. So after all of that, like, really thinking about, you know, what are things that can help the brain overall? And along the way, during that time when my kids were sick, I got introduced to the idea about ketogenic diets and brain health and really took note of that.

[00:11:04 –> 00:11:45] Dr. Matt Bernstein: My mind was already kind of blown open by our experience and, you know, started looking into the research on that. And it’s extensive research, about ketogenic diets going back to 1921 when the ketogenic diet was invented at the Mayo Clinic for to treat pediatric epilepsy. And, you know, it was really this treatment of choice for decades until the drugs really started coming online and people are enamored with with medications because they’re so much easier to prescribe than a diet. Then there’s a real resurgence of the ketogenic diet and epilepsy in the nineteen eighties, and they started doing more research. And what they found is that it’s really effective in medication resistant epilepsy.

[00:11:46 –> 00:12:21] Dr. Matt Bernstein: You know? So these kids who are on three different antiepileptic drugs at the same time still having seizures, the ketogenic diet works in the majority of time in those kids to significantly reduce seizures. And some of these kids have such good outcomes from it that they can come off all their anti seizure drugs and be almost seizure free. Some of them even can only need the diet for a few years, come off of the diet, and still retain the seat most of that seizure control even off the diet. So there seems to be a healing process in pediatric epilepsy from this ketogenic diet.

[00:12:21 –> 00:12:35] Dr. Matt Bernstein: So that’s really, really interesting, you know, to think about. You know, we don’t have a lot of things that can truly heal a severe disorder in the brain. We have things that treat symptoms, obviously. Right? But we don’t have things that heal the brain.

[00:12:35 –> 00:12:37] Dr. Matt Bernstein: So I really took note of that when I learned about it.

[00:12:38 –> 00:12:40] Dr. Ravi Kumar: Yeah. That’s fascinating. I mean, that’s been around for a 100.

[00:12:40 –> 00:12:41] Dr. Matt Bernstein: Right.

[00:12:41 –> 00:12:52] Dr. Ravi Kumar: This fact the fact that a ketogenic diet, which is where you basically restrict carbohydrates and you start metabolizing ketones as your primary energy source. Well, sorry. It’s just incorrect.

[00:12:52 –> 00:13:22] Dr. Matt Bernstein: Yeah. You start metabolizing fatty acids as your primary energy source, And and and and fatty acids can’t cross the blood brain barrier because they’re too big. So the body chops up those fatty acids into little smaller particles, ketones, that can cross the blood brain barrier. And so they’re really ketones are designed by our body through evolution. We we have the ability to make them when we were in periods of low food so that the brain would function really well even though there was no food.

[00:13:22 –> 00:13:57] Dr. Matt Bernstein: This is a survival mechanism that are, you know, that has developed through our evolutionary history. And our our brains, through evolutionary history, were used to seeing ketones a lot of the time. We evolved with ketones in our you know, our brain seeing ketones for many parts of the year when there wasn’t enough food. And and through agriculture and mod especially in the last hundred years, you know, people aren’t making ketones anymore eating the standard American diet and and being fairly sedentary. There there’s almost zero ketones being made unless you purposefully do something now to to get your body to make ketones.

[00:13:57 –> 00:14:10] Dr. Matt Bernstein: But it it wasn’t always the case. People think about it like this is this odd metabolism or this odd source of fuel, but it’s absolutely how our bodies and our brains are used to you know, from an evolutionary point of view, this is what we’re used to.

[00:14:10 –> 00:14:54] Dr. Ravi Kumar: It’s part of our evolutionary design to yeah. Exactly. Like you said, metabolize fatty acids, break them down into ketone bodies, deliver those to the brain, which feed into the, electron transport chain just like the products of glucose do, but with less oxidative injury, with less inflammation. And I think there’s even data that says that say that ketones actually stimulate NRF2 in this whole anti inflammatory cascade. So it’s like we we basically evolved to periodically depend on ketone energy metabolism so that we could kinda clear the the metabolic field a little bit and and basically operate more efficiently, and and that doesn’t happen anymore.

[00:14:54 –> 00:15:08] Dr. Ravi Kumar: And so you you know, here we are. We’re finding out that this has plays a big role in neurological health. So you you got this seizure data. Yeah. How how did you then or did your field then take that into saying, hey.

[00:15:08 –> 00:15:14] Dr. Ravi Kumar: Maybe these other neurological disorders could also be helped by a ketogenic diet.

[00:15:15 –> 00:15:25] Dr. Matt Bernstein: Absolutely. Yeah. And and I just wanna mark we’ll get back to it later. Maybe there’s a couple other mechanisms. You started talking about mechanisms, and there’s more about mechanisms that I’d love to come back to.

[00:15:25 –> 00:15:26] Dr. Ravi Kumar: Okay. Let’s do it.

[00:15:26 –> 00:15:51] Dr. Matt Bernstein: But let’s stick with clinical for a bit, and then we’ll come back to mechanisms. So the first study on mental health with ketogenic diets was actually in the mid nineteen sixties. It was a case series of women with schizophrenia, and they gave them a ketogenic diet, and it was actually remarkably helpful. And then the field just completely forgot about it. That’s around the same time that the psychiatric medications were coming online, and people were you know, of course, it’s a lot and and everyone knows.

[00:15:51 –> 00:16:08] Dr. Matt Bernstein: I mean, we know this. Patients know this. It’s a lot easier to take a medication than completely change your diet. And certainly for doctors who weren’t trained in nutrition very much were much more comfortable prescribing a medication than prescribing a diet. So, you know, it’s not a surprise that people didn’t really pay attention to that.

[00:16:08 –> 00:16:49] Dr. Matt Bernstein: People started paying attention again in around 2017, 2018. There’s there’s a psychiatrist who I happen to know well from residency, Dr. Chris Palmer, who started publishing case reports about people with treatment resistant psychosis recovering almost completely or sometimes dramatically and completely on a ketogenic diet and being able to come off of all their medications despite having sometimes years and years of psychosis. I mean, these are things that people, you know, wouldn’t otherwise even believe. And in fact, you know, that’s how I learned about the diet. I was sitting in a grand rounds lecture at McLean Hospital in this, you know, staid, you know, fancy lecture hall with, like, the wood panels.

[00:16:49 –> 00:17:10] Dr. Matt Bernstein: And and Chris Palmer was giving a lecture about ketogenic diets and mental health and the hit this history that we’re talking about with epilepsy. And I sometimes joke that I’m you know, out of the probably about a 150 people in the room, I might have been the only one who actually, like, fully was on board with what he was saying. Because at the time, it just sounded like, what is he talking about? Yeah. You know?

[00:17:10 –> 00:17:29] Dr. Matt Bernstein: This is very hard to believe. A diet’s gonna work better than clozapine, our most, you know, powerful antipsychotic drug. It’s gonna allow someone who couldn’t even get well on clozapine to get well from, you know, fifty years of psychosis. That doesn’t sound believable. But, you know, I believe Chris.

[00:17:29 –> 00:17:54] Dr. Matt Bernstein: And and in fact, now I’ve seen those types of things happen many times in my own hands. So, you know, it took a little while for me to come back to that because like I said, I learned about this kind of early on in my kids’ experience. We were still in the midst of it. And then, you know, I came back to it because I realized that there’s really some really good science to this. There’s really good reason to believe that this works based on a mechanistic point of view, and we’ll get more into the mechanisms later.

[00:17:54 –> 00:18:30] Dr. Matt Bernstein: But just based on these early case reports and case series, and then, you know, I just started you know, when I started having the wherewithal, first, I put myself on a ketogenic diet just to see what it’s like and how hard is this really to do. It’s a little bit challenging when you first do it. I don’t want to sugarcoat that, you know, not to use a pun, but, you know, it’s not that easy when you first start eating that way. When we’re used to eating this certain way, our our bodies are used to having carbohydrates all the time. Most of us have developed some amount of insulin resistance, and we’re we’re essentially what they call metabolically inflexible.

[00:18:30 –> 00:19:07] Dr. Matt Bernstein: We are not used to using fatty acids, when our our livers are not used to making ketones, it takes a little time to adapt to it and to start feeling the benefits of it. But once I did, I felt incredibly different than I did before. I mean, it the the the the change was really remarkable to feel the cognitive benefits, the energy benefits, the benefit of not feeling like I needed to eat all throughout the day to be able to keep my brain running, which is exactly what was happening to me. I mean, in retrospect, I think I was very insulin resistant. Not that any doctor ever checked my insulin resistance.

[00:19:07 –> 00:19:24] Dr. Matt Bernstein: And no you know, it’s not part of our standard annual physical exam to check a fasting insulin or a HOMA IR. And it’s a cheap test, and it’s so informative, but no one no one had checked. But but in retrospect, I know I was insulin resistant because I needed to eat every few hours to keep my brain going.

[00:19:24 –> 00:19:41] Dr. Ravi Kumar: Yeah. So you you tried out the ketogenic diet, and you saw significant benefits for your brain health, but you don’t have psychiatric illness. Yeah. You just had this idea that, hey. Chris Palmer over at Harvard is doing these studies or showing these case reports with significant improvements.

[00:19:42 –> 00:19:48] Dr. Ravi Kumar: So did you eventually start trying this in your practice? Yeah. Is that what you your next step?

[00:19:48 –> 00:20:04] Dr. Matt Bernstein: That’s exactly right. Next step was I started talking to people who I’d been working with for years who I thought were might be open to trying this and started trying to convince them to completely change their diet and see how much that might improve their brain health and their mental health.

[00:20:04 –> 00:20:06] Dr. Ravi Kumar: Was that a hard sell?

[00:20:06 –> 00:20:17] Dr. Matt Bernstein: For some of them. Yeah. I mean, first of even the ones who eventually did it were looking at me like I like, they were like, what happened to you? You know? You some something has changed.

[00:20:17 –> 00:20:32] Dr. Matt Bernstein: You know? Why are you talking to me about this instead of what we normally talk about? So it it was very different and like a little jarring for for for folks, including myself. But, you know, I did start convincing people to do it. And, again, I just started seeing these dramatic benefits.

[00:20:32 –> 00:21:04] Dr. Matt Bernstein: And depending on the severity of people’s condition or their own individual situation, you know, sometimes more dramatic than others. But pretty universally, I was seeing people have more energy, more vitality, better cognitive health, better memory, better mood. And often, even in these more severe conditions like psychosis and bipolar, we were seeing really significant improvements in those symptoms as well. Okay. Meanwhile, people are feeling really good about the fact that they were able to lose some of the weight that they had put on from these psychiatric medications.

[00:21:04 –> 00:21:26] Dr. Matt Bernstein: Their lab work was looking a lot better almost universally. And so for the people who could do it, we were and, you know, I was really happy with the results, and they were as well. So it was like, you know, really made me feel like I wanna keep going. Like, you know, more people need to know about this, and and and I wanna, you know, have a way for more people to be able to try this. Okay.

[00:21:26 –> 00:21:56] Dr. Matt Bernstein: Because it is you know, it’s it’s a challenging thing to do, as I was saying, even for myself. For someone who’s already struggling with a severe mental health condition, it’s a lot to ask of people Yeah. To to to change and start measuring what they’re eating, really paying attention exactly what’s on the labels, or really cooking a lot more from scratch, not eating out, not eating packaged foods, starting to exercise. You know? Because ideally, you know, we it’s it’s the diet plus these other interventions.

[00:21:57 –> 00:22:23] Dr. Matt Bernstein: The more of these other interventions I can get people to do, you know, often the faster their recoveries are. And so, you know, eventually decided that I was gonna open up a whole program that was all about this. And so a little over two years ago, we opened a program called Accord, outside of Boston, where it’s an immersive program where people come, and it’s a residential setting. So people can live there, or they if people are local, they can just come in for the whole day. And we’re providing the food.

[00:22:23 –> 00:22:47] Dr. Matt Bernstein: We have a really great chef and a dietitian. We’re getting people walking a few times a day outside in the sunlight. We’re getting people in the gym multiple times a week, working out with a personal trainer, and we’re measuring everything. So we’re measuring their ketones, and we’re measuring their glucose with a CGM and body composition. And we’re measuring lots of lab work every month to make sure everything’s going well and rating scales.

[00:22:47 –> 00:23:16] Dr. Matt Bernstein: And we’re seeing just, you know, really incredible benefits from the people who come to to do that program. And and the goal is to teach people how to do it when they get home too. So Right. Lots of education along the way and cooking lessons and lessons for me about the metabolism and the science and how it works. And lots of groups with our our social worker about, you know, the the resistances that come up, you know, because we’re all very psychologically attached to the foods that we eat, and there’s a lot of cultural components too.

[00:23:16 –> 00:23:31] Dr. Matt Bernstein: So it’s complicated. And and like I said, it’s not it’s not easy. But for the people who are motivated to wanna change their health and take control over their health, especially their mental health in this way, it’s it it it really does work.

[00:23:32 –> 00:23:53] Dr. Ravi Kumar: Yeah. So, I mean, exercise and, sunlight and good sleep and all those things you mentioned are fantastic holistic parts of maintaining good mental health. But as far as ketones go, the only being in ketosis, the only way you get into it is through a specific type of diet. Correct? Yes.

[00:23:53 –> 00:23:53] Dr. Matt Bernstein: Yes.

[00:23:53 –> 00:23:59] Dr. Ravi Kumar: So I mean what are you doing for them? Like, what how are you having them eat to to get into that state that’s therapeutic for the brain?

[00:23:59 –> 00:24:33] Dr. Matt Bernstein: Right. So so we we classified ketogenic diets by the ratio of the grams of fat to the grams of carbohydrates and protein combined. And initially, it you know, when they first invented the ketogenic diet at the Mayo Clinic in 1921, they were using a very, very high ratio. They thought they needed that. So it was four to one ratio, and that means essentially, you know, 90% of the calories were coming from fat, which is a really hard diet to eat as you can imagine.

[00:24:33 –> 00:25:01] Dr. Matt Bernstein: I mean, your plate has very little substance. It’s just fat, basically. Now we generally start people off on a one to one ratio, and then we see with that plus all the other interventions, you know, how high of a level of ketosis they can get into. We sometimes are going up to a 1.5 to one or a two to one ratio for some people, but we almost never need to go above a two to one, and we can get very high levels of ketones with a two to one ratio. And so it’s

[00:25:01 –> 00:25:04] Dr. Ravi Kumar: And this is a ratio of calories, or is it a ratio of weight?

[00:25:04 –> 00:25:11] Dr. Matt Bernstein: It’s a ratio of grams of fat compared to grams of protein and carbohydrates combined.

[00:25:11 –> 00:25:15] Dr. Ravi Kumar: So ratio of weight of fat versus carbs and protein.

[00:25:16 –> 00:25:16] Dr. Matt Bernstein: So

[00:25:16 –> 00:25:26] Dr. Ravi Kumar: you’re eating whatever in a meal, 50 grams of fat, 50 grams of protein and carbs combined. Yeah. That sounds like a small meal, but like that. Right. That would be a

[00:25:26 –> 00:25:28] Dr. Matt Bernstein: one that would be a one to one ratio. Right.

[00:25:28 –> 00:25:29] Dr. Ravi Kumar: Okay. And

[00:25:29 –> 00:25:39] Dr. Matt Bernstein: and out that 50 grams of carbs and fat combined, probably most of that is I’m sorry, carbs and protein combined, probably most of that is protein because we are still keeping the carbohydrates very low.

[00:25:40 –> 00:25:41] Dr. Ravi Kumar: Okay.

[00:25:41 –> 00:26:03] Dr. Matt Bernstein: And and we don’t wanna you know, in that really high ratio diets, you you would almost, you know, have to have a low protein diet. And we don’t want people to have a low protein diet. We’re we’re looking for people to build muscle. So we’re trying to keep the protein at around, you know, 1.2 grams per kilogram per day at least. When we get up to this, like, two to one ratio, sometimes, you know, that’s a little more challenging to keep the 1.2 gram ratio.

[00:26:03 –> 00:26:35] Dr. Matt Bernstein: At a one to one ratio, we can have a 1.6 grams per kilogram protein per day. And that’s ideal for building muscle, which is often very, very helpful for overall metabolic health, and it’s very helpful for the brain. You know, the muscle sends these myokines signals to the rest of the body, and the brain receives myokines. So when the muscles are healthy and active, the brain receives this positive signal from the muscles, to also, you know, grow and be and be healthy. And, you know, evolutionarily, that makes a lot of sense too.

[00:26:35 –> 00:26:53] Dr. Matt Bernstein: Right? When the organism is doing well enough to have enough protein and to be moving around enough, you know, it’s that means muscle will be made. Muscle is very metabolically expensive. That means the rest of the body should get the signal that we’re in good times here. Let’s let’s grow and build and do all the right things.

[00:26:53 –> 00:26:53] Dr. Matt Bernstein: Right?

[00:26:54 –> 00:27:03] Dr. Ravi Kumar: Right. I I know some people are resistant to going into ketosis just genetically. Some people go straight into ketosis. Some people Yeah. They have to work a lot harder.

[00:27:03 –> 00:27:11] Dr. Ravi Kumar: Now do you measure where you want to be strictly on ketones, or are you seeing if there’s a clinical response and saying, hey. You’re not in ketosis, but you’re one to one and you’re doing good?

[00:27:11 –> 00:27:28] Dr. Matt Bernstein: It’s a little bit of both. Yeah. A little bit of both. You know, one thing that we’ve learned about ketones is that they really fluctuate a lot throughout the day. So any measure that you’re measuring once a day that is fluctuating by sometimes an order of factor of 10, believe it or not.

[00:27:28 –> 00:28:00] Dr. Matt Bernstein: You know, you need to be a little careful about what that number means. I’ll give you an example. So we sometimes get our hands on some continuous ketone monitors. We don’t unfortunately, they’re not approved in The US, but occasionally, people get get their hands on them. And so when someone’s wearing a CKM, I’ve seen curves where they’re mourning you know, right after their cortisol surge when they’re first waking up, their ketones are at their lowest, and they might be down at, like, point four of for beta hydroxybutyrate, which is not really therapeutic ketosis quite.

[00:28:00 –> 00:28:28] Dr. Matt Bernstein: Like, we we started at point five, but really for a lot of people, we want it above one. But that same person in the middle of the night might have their ketones be up to four and a half same day, you know, in within twenty four hours. And so if we just get one measure in the afternoon because we do have to prick someone’s finger and people don’t like to measure it, you know, four times a day, it’d be nice data, but, like, that’s a little impractical for people. So we just have to be a little circumspect about making too much about those ketone numbers. And so we you know?

[00:28:28 –> 00:28:55] Dr. Matt Bernstein: And, ultimately, the most important thing is clinical response. So if someone’s having a great clinical response, but their afternoon beta hydroxybutyrate is, you know, point four or point five or point six, but they’re feeling better than they ever have, you know, I don’t see any reason to try to keep pushing the ketones up. But sometimes people want to see. Well, I still want to see what it feels like to get my ketones above, you know, one or above two or even above three. And it’s doable for everyone.

[00:28:55 –> 00:29:20] Dr. Matt Bernstein: It just might require some more behavioral interventions, maybe a little tweak of the diet. Often more exercise will make a big difference for people in terms of their ketones. But also lowering stress makes a huge difference. A poor night one poor night of sleep and your ketones will be thrown off the next day, as will your CGM curve. So all these other factors are really powerful for what’s going on with metabolism, and and it’s very quick.

[00:29:20 –> 00:29:40] Dr. Matt Bernstein: They’re it’s all responsive in real time of what’s going on. You know, a good example of that would be we will see someone, you know, wearing a CGM where their glucose will spike. You know? And on a ketogenic diet, typically, we’re seeing glucose is somewhere between, you know, sixty and ninety throughout the day. Doesn’t change much.

[00:29:40 –> 00:29:50] Dr. Matt Bernstein: Mhmm. The the very flat line glucose curves. All of a sudden, their glucose spikes to a 130 or a 140. And, you know, first question is, well, did you eat anything different? No.

[00:29:50 –> 00:29:56] Dr. Matt Bernstein: You know, they they they’re just been at the house all day. They haven’t eaten anything different. Are are you anxious? Yeah. I’m really anxious.

[00:29:56 –> 00:30:06] Dr. Matt Bernstein: This thing just happened. You know, I got this call. I’m freaking out. I’m almost in a panic attack. And, you know, that’s why their glucose is at a 140 just from stratonins.

[00:30:07 –> 00:30:14] Dr. Matt Bernstein: If they do a mind body practice, it comes right down. Like, literally within five minutes of some deep breathing, slow breathing, it’ll comes right down.

[00:30:14 –> 00:30:24] Dr. Ravi Kumar: Yeah. That’s fascinating, actually. Yeah. Yeah. So, I mean, they’ve at this point, they’ve exhausted their most of their glycogen stores because they’re eating such a low carbohydrate diet and they’re exercising.

[00:30:24 –> 00:30:28] Dr. Ravi Kumar: Yeah. So where are the where’s that glucose coming from? Is it coming from protein breakdown?

[00:30:29 –> 00:30:45] Dr. Matt Bernstein: It’s gluconeogenesis. Yeah. So when someone’s you know, if you’re eating a very low carbohydrate diet or near zero carbohydrate diet, your glucose stays steady. Your body knows how to make it from gluconeogenesis Mhmm. Which essentially is from protein and cholesterol.

[00:30:45 –> 00:31:09] Dr. Matt Bernstein: And there’s parts of our brain that that run on glucose no matter how many ketones you’re making. We’re never our body will protect our glucose into in a range almost at all costs. So, you know, if someone’s really not eating enough, the you know, you just start breaking down your muscle. The the goal is obviously is to have enough ketones and enough fatty acids so that we’re not gonna be breaking down muscle. And as I was saying, one of our big goals is building muscle.

[00:31:09 –> 00:31:15] Dr. Matt Bernstein: And and if you do this right, there’s no reason why your your your body needs to keep breaking down muscle. Yeah.

[00:31:15 –> 00:31:30] Dr. Ravi Kumar: Okay. So let’s say that and I think it’s important to tell the audience, yeah, you you don’t become hypoglycemic on a ketotic diet. If you do, you’re you’re very symptomatic, and it’s bad for you. So our brain needs glucose. Certain, tissues in our body need glucose.

[00:31:30 –> 00:31:52] Dr. Ravi Kumar: It’s part of normal metabolism, but ketones can be an alternative fuel that can kinda clean up the metabolic system, and we’ll talk about that a little later. But Yeah. With these diseases that you’re treating, like OCD, schizophrenia, bipolar, depression Yep. I know you say you’re seeing good results, but can you kind of be give us a little bit more detail on that? Like, are people getting off their medications?

[00:31:52 –> 00:31:56] Dr. Ravi Kumar: Are they going into remission? I mean, how well are they actually doing with this?

[00:31:57 –> 00:32:09] Dr. Matt Bernstein: Yeah. I mean, I can talk about some of my results. I can talk about some of the the studies too because we did now have more research about this. Yeah. And so so maybe we’ll start with some studies, and then, you know, I can talk about some more individual situations too.

[00:32:09 –> 00:32:23] Dr. Matt Bernstein: Okay. So there there’s a really great study. It’s considered a pilot trial. Dr. Shivani Sethi at Stanford did came out a couple of years ago. She took people with really severe mental health issues, outpatients.

[00:32:24 –> 00:33:00] Dr. Matt Bernstein: In this study, they actually taught them how to do the ketogenic diet. They didn’t provide all the food, so it was a proof of concept that, you know, people with serious illness can learn how to cook this way and eat this way and and get into ketosis, which they proved. And this is a single arm trial, so no control group, just to be just to be clear. But they had incredible metabolic benefits. You know, all the people who had metabolic syndrome were taken out of metabolic syndrome, huge reductions in triglycerides, increase in HDL, blood pressure improvements, visceral fat improvements, you know, and anything you can think of that you’d want to see from a metabolic perspective happen, you know, hemoglobin A1c improvements.

[00:33:00 –> 00:33:30] Dr. Matt Bernstein: And then really striking mental health improvements. They they were using this scale that was about remission, essentially, you know, having low enough symptoms that you weren’t considered really symptomatic again. And they had really striking improvements to the point where everyone who was actually adherent with the diet, fully adherent with the diet, got into remission from their mental health disorder. So and these are yeah. Again, people with schizophrenia, and I believe it was bipolar, schizophrenia and bipolar in that in that trial.

[00:33:31 –> 00:33:31] Dr. Ravi Kumar: That’s amazing.

[00:33:32 –> 00:33:56] Dr. Matt Bernstein: Yeah. So that was incredible. There’s another really great study that I like to talk about from 2022 is inpatients in France. The the lead author is Danan, and he was an inpatient doctor for decades, had the same population, very chronic, people coming in and out of the hospital, big medication regimens. People are very, you know, considered, well, this word treatment resistant, which I I really don’t like that term at all in psychiatry.

[00:33:56 –> 00:34:39] Dr. Matt Bernstein: And he put a series of people, I think about 31 in a row on the ketogenic diet on the inpatient unit. And, the rating scale reductions were just absolutely incredible. So they were measuring things like the MADRS and the Hamilton depression scale, and then the PANSS, which is the psychosis rating scale, and the CGI, which is like a global clinical impression of psychiatry. Again, single arm trial, no control group, but the Cohen’s d numbers for the change, which is the the effect size, were above three for all of those rating scales. And in psychiatry, you know, we’re happy, you know, when a medication like SSRIs average about point three five compared to placebo.

[00:34:39 –> 00:35:05] Dr. Matt Bernstein: Antipsychotics average about point five or point six compared to placebo. They’re getting he’s getting effect sizes of three, three and a half, like, on these rating scales. Like, we just we don’t see that in psychiatry. And then they they also had metabolic improvements, and they were discharged on less medication than they came in on, which again is, you know, never seen on inpatient units. People never get discharged on less medication than they came in on in in psychiatry.

[00:35:05 –> 00:35:11] Dr. Ravi Kumar: So, you know Or any other field, by the way. Right. They all come into the they all leave the hospital with more medications they came in with.

[00:35:11 –> 00:35:33] Dr. Matt Bernstein: Yeah. Which is, you know, really really it says a lot about medicine. But, anyway, so those are just a little taste. There’s other trials I could talk about. There’s a randomized controlled trial, partially randomized controlled trial that just came out from UCSF just this year that also showed some some really nice improvements in the pans at four months once they were unrandomized.

[00:35:34 –> 00:36:11] Dr. Matt Bernstein: And they did have some metabolic improvements in one month, but one month is just not enough probably to see the the mental health changes. And there’s another big trial on treatment resistant depression that came out recently by, an author named Gao in The UK, where they randomized this was a randomized controlled trial, ketogenic diet versus a controlled diet. And they did see a really nice signal of improvement in treatment resistant depression at six weeks from the ketogenic diet. And then what they also saw was that people stopped doing the diet after six weeks because they didn’t really teach them how to do it. And they were just providing the meals.

[00:36:11 –> 00:36:27] Dr. Matt Bernstein: So that illustrates another important point is that part of what we need to do in in the medical world when we when we prescribe a diet is we actually have to teach people how to do the diet. That that can’t be ignored or forgotten. Yeah. Okay. So, anyway, that’s a bit about the literature.

[00:36:27 –> 00:36:28] Dr. Matt Bernstein: I don’t know if you wanna pause there for a second.

[00:36:29 –> 00:36:44] Dr. Ravi Kumar: I think one comment on all that is that medication is not always the solution. I am not anti medication. I prescribe it all the time. But there are diet and lifestyle factors that can be so powerful. Right.

[00:36:44 –> 00:37:03] Dr. Ravi Kumar: That if we could ever bottle it put it in a pill and bottle it up, they’d be blockbusters. Absolutely. They they would be the most effective, most valuable drugs ever invented. But that’s not that’s not the case. They’re free most of the time, interventions that don’t require a prescription that you can do at home.

[00:37:03 –> 00:37:04] Dr. Ravi Kumar: So when you

[00:37:04 –> 00:37:07] Dr. Matt Bernstein: But they’re also hard to do. Right? So They’re

[00:37:07 –> 00:37:14] Dr. Ravi Kumar: they can be sometimes. Yeah. Or maybe walking once a day for thirty minutes, that’s not hard. But, yeah, the ketogenic diet, for sure, that lands

[00:37:14 –> 00:37:23] Dr. Matt Bernstein: on I that mean, this is illustrated in the literature on exercise for depression, which is a really interesting literature. I mean, it’s just worth maybe taking a little detour about that.

[00:37:24 –> 00:37:25] Dr. Ravi Kumar: Okay. Yeah.

[00:37:25 –> 00:37:48] Dr. Matt Bernstein: So, I mean, there’s been more than a thousand trials of exercise for depression. I mean, it’s really well studied. So, you know, we can say a lot of this with a lot of confidence. When they do meta analyses, they’re including like over a thousand trials. And generally, what we find is that, you know, intensive exercise for depression is significantly more effective than antidepressants.

[00:37:48 –> 00:38:06] Dr. Matt Bernstein: You know, I was talking about the Cohen’s d for antidepressants, about point three five. It it’s up to closer to about point 7.8 Cohen’s d for for exercise. But it has to be pretty intense exercise. And in those trials, there’s huge dropout rates. Right?

[00:38:06 –> 00:38:40] Dr. Matt Bernstein: You can’t get really depressed people to exercise intensively very easily. That is not easy. I mean, don’t know. For the people in the audience who have been depressed, it’s very, very hard to get up and make breakfast or even get up at all and get out of bed, let alone walk for thirty minutes, which would be great place to start, but even more so to really do an intensive exercise regimen like a, you know, in high intensity interval training or, you know you know, good long cardio session or a weightlifting session. I mean, these are the types of things that really move the needle for people.

[00:38:40 –> 00:39:06] Dr. Matt Bernstein: And, you know, I believe in staunchly, but they’re really hard to get people to do. And so, you know, we know it’s effective. It’s measured to be extremely effective. It’s just, you know, in clinical practice, you know, psychiatrists who tell their, you know, patients to, you know, you could exercise or you could take this pill. We often don’t end up in the exercise part of that part of that equation.

[00:39:06 –> 00:39:38] Dr. Matt Bernstein: And you can say that’s a because of the illness. You can say it’s because we’re not trying hard enough to make this accessible to people. I mean, that’s the other argument that we can make is that, you know, instead of the insurance company paying for a many $100 a month prescription, they ought to be paying for a personal trainer or a group training session that someone could go to three times a week. That could be overall better for someone’s depression, but overall better for their health, and in the end, probably more cost effective. Yeah.

[00:39:38 –> 00:39:52] Dr. Ravi Kumar: I mean, apathy is part of the depressive symptoms. Right? That That’s apathy prevents you from doing the things that make you better, and it becomes this vicious cycle. I mean, they even have, you know, behavioral activation. It’s super, super effective.

[00:39:52 –> 00:39:52] Dr. Matt Bernstein: But it’s

[00:39:52 –> 00:39:58] Dr. Ravi Kumar: it’s patients can’t do it. That’s the problem. You know? Because you Yeah. It takes a a second to pop a pill.

[00:39:59 –> 00:40:08] Dr. Ravi Kumar: Behavioral activation might work better, but to activate is like almost like climbing a mountain for patients who are depressed. So I totally understand that, and I I thanks for bringing

[00:40:08 –> 00:40:33] Dr. Matt Bernstein: that up. These things do work. It’s just that they and and it’s not that you can’t get someone to do it. It’s just that it requires a lot of clinician time and energy, and that’s cost money. And people would rather invest in it seems that the you know, from what I can see, the insurance companies would rather invest in that extremely expensive pill than invest in these other types of behavioral solutions.

[00:40:34 –> 00:40:46] Dr. Matt Bernstein: Right. Because, you know, they won’t pay for someone to come to your house and, you know, grab you out of bed and take you to go exercise, but they will pay for a pill that could be, you know, hundreds of dollars a month or even, you know, a couple thousand dollars a month sometimes.

[00:40:46 –> 00:40:55] Dr. Ravi Kumar: Yeah. So And causes you to and causes you to gain weight, lose your sex drive. You know? I mean I mean, those are potential side effects of some of these medications that

[00:40:55 –> 00:40:55] Dr. Matt Bernstein: That’s right.

[00:40:55 –> 00:41:08] Dr. Ravi Kumar: End up feeding into that vicious cycle. And I think that kind of speaks to what you had mentioned before that short term, there there’s some benefit, but long term, there may be some side effects to these medications that negate immune system benefit.

[00:41:08 –> 00:41:34] Dr. Matt Bernstein: It’s not just maybe. I mean, yeah, that that’s well documented. The, the metabolic side effects are well documented in many of these medications. Even I mean, people think that some of them are safe, like, you know, safer and there are some that are safer than others, but even the ones that are considered safe have a pretty strong negative metabolic signal. Even even SSRIs, which people don’t think about as being that metabolically harmful, there’s there’s a real signal about them being, metabolically harmful as well.

[00:41:34 –> 00:41:48] Dr. Ravi Kumar: Yeah. Okay. So let’s talk about what we’ve talked about the literature, and and it’s the literature is pretty impressive, honestly. What have you seen in your personal practice with this diet and lifestyle changes in ketosis? So

[00:41:48 –> 00:42:16] Dr. Matt Bernstein: what I’ve seen is is that when someone does the ketogenic diet, gets themselves truly into ketosis, and can add on some of these other aspects of this whole program, I’m seeing universal benefits. It can take a little time sometimes. You know? It doesn’t always happen in the first few weeks. And what we say to people is that, you know, if you really wanna give this a try, you know, you gotta be in ketosis for about three months to really know.

[00:42:17 –> 00:42:37] Dr. Matt Bernstein: I’ve yet to see someone in ketosis for three months who’s come back to me and say, I’m not feeling anything. I just haven’t seen that yet. Now there are people who can’t make it to the three months, and they quit before they get there, and and they haven’t felt something. So, I mean, that’s that’s real. But when people are in ketosis, physiology changes in a in a big way.

[00:42:37 –> 00:42:52] Dr. Matt Bernstein: And especially for people with a mental health issue, things start to change in a positive way. I just I I see that as almost a almost universal thing. It just can take a while. You know? Sometimes it takes some time for, you know, the the brain to come back online.

[00:42:52 –> 00:43:03] Dr. Matt Bernstein: And, again, that gets back into some of the mechanisms that we’ll get into, that some of these are quick mechanisms, but some of them are are you know, these signaling parts can take some time to, I think, really, you know, create those changes.

[00:43:04 –> 00:43:12] Dr. Ravi Kumar: Yeah. So what what about children? I know most of these patients you’re treating are probably adults, but can children get the same benefits as as adults?

[00:43:12 –> 00:43:51] Dr. Matt Bernstein: So I I personally am not treating kids, but there is some literature, and there’s definitely some studies going on right now in pediatric bipolar disorder using ketogenic diets. Certainly, the the vast amount of literature on ketogenic diets for the brain are in kids because we the pediatric epilepsy literature is still much bigger than the mental health literature. And so we know it’s a safe diet for kids, because of that. And so, you know, I think, you know, for a kid with a mental health problem and, you know, in retrospect, I wish I knew all of this when my kids first got sick because that would have been the first thing that I would have done is put them on a ketogenic diet. And and I and I don’t know if that would have worked, but but I wish I I knew this then.

[00:43:51 –> 00:43:55] Dr. Matt Bernstein: I wish I I wish that’s what we had had done first. Yeah. Yeah.

[00:43:55 –> 00:44:16] Dr. Ravi Kumar: And I think it’s important to note here that the things that you’re talking about have such inherently low risks. That’s right. You know, we we always talk about interventions to get better, and oftentimes there’s a risk and there’s a benefit and there’s a ratio between the two and you decide what to do. I mean, what I do is high risk, high benefit, you know, with neurosurgery. But Right.

[00:44:16 –> 00:44:28] Dr. Ravi Kumar: What you’re talking about is extraordinarily low risk, extraordinarily high benefit, And those risk benefit ratios like what you’re talking about are not very common in medicine

[00:44:28 –> 00:44:39] Dr. Matt Bernstein: That’s right. Honestly. No. I I completely agree, and I think you’re making an excellent point that that is a rare combination. And it’s partly why I’m so excited about it.

[00:44:39 –> 00:45:21] Dr. Matt Bernstein: Because I’ve been prescribing medications that are incredibly risky for my whole career and telling people that they don’t have that much of a choice here. Like, if you want to treat your bipolar disorder or your schizophrenia or your severe OCD, you kind of have to take, you know, one of these medications that is gonna have likely some pretty significant side effects, risks of tardive dyskinesia, neurological side effects, but also these, you know, metabolic risks we’re talking about. And some of the ones I prescribe, you know, have some, you know, really dramatic risks like agranulocytosis with clozapine. And, you know, I’ve seen that happen a few times. I’ve seen Stevens Johnson syndrome with lamotrigine a couple of times.

[00:45:21 –> 00:45:55] Dr. Matt Bernstein: I mean, these are these are really scary things to to see. And and, you know, I I used to have to say, and I felt like it was the right thing to say that, you know, it’s still the best thing to do. Take these risks because, you know, the alternative is, you know, you’ve got this untreated illness that that is gonna be out of control and really, you know, get in the way of your functioning, and potentially cause harms. Now I feel like, well, I’m so excited. I have something to offer people that’s not a high risk that, yes, it requires work, but the rewards are almost certainly going to come and the risks are low.

[00:45:56 –> 00:46:11] Dr. Ravi Kumar: Yeah. Okay. So honestly, I tell all my audience, if you can find something that’s low risk, high benefit, why not? Mean, there’s there’s very there’s very little reason not to do that. Let’s talk about mechanisms here because I think this is what is really fascinating.

[00:46:11 –> 00:46:35] Dr. Ravi Kumar: And I also think that once people understand how something works, it’s actually easier to do because they’ve rationalized why it should work. They understand why it should work. And then often they realize the benefit because of that, because they know that it works and they know how it works. So tell us what is actually happening in the brain when you go into ketosis that’s offering these benefits that you’re seeing.

[00:46:35 –> 00:46:42] Dr. Matt Bernstein: Right. Well, you you had already mentioned a number of them. You know? So, you know, there it is this additional source of fuel. Right?

[00:46:42 –> 00:46:54] Dr. Matt Bernstein: Let’s think about what that means. So there are certain areas of the brain. There’s there’s there’s different glucose transporters. You know? There’s the GLUT one transporter, the GLUT three transporter, the GLUT four transporter.

[00:46:54 –> 00:47:09] Dr. Matt Bernstein: These are different ways for the cell to get glucose from the extracellular space inside the cell. And some of those transporters don’t need insulin. You know, GLUT one and GLUT three, for example. And many parts of the brain can just have glucose enter the cell. No need for insulin signal at all.

[00:47:09 –> 00:47:40] Dr. Matt Bernstein: No problem. But there’s some areas of the brain that do require an insulin signal for the glucose to get into the brain. These areas that require that rely on the GLUT four transporter. And when those areas of the brain become insulin resistant, that insulin signal doesn’t get through, and those neurons are starving for energy despite the fact that there may be lots and lots of glucose in that extracellular space. And those areas of the brain happen to be the areas that are incredibly relevant here.

[00:47:40 –> 00:48:02] Dr. Matt Bernstein: So, I mean, we’re talking about the, you know, the hypothalamus, the hippocampus, and the amygdala. You know, three of the most important regions for what I do, you know, for mental health. Right? And so those areas of the brain are insulin resistant due to a variety of factors. You know, they can even start becoming insulin resistant in childhood.

[00:48:02 –> 00:48:35] Dr. Matt Bernstein: And, you know, especially due to a lot of stress, genetic factors, maybe some medications, metabolic lifestyle factors that lead to metabolic disruptions and insulin resistance going on in the rest of the body anyway. All that’s gonna be more likely for those areas to become insulin resistant. And so if that’s happening, those areas, which are so important for cognition and memory and mood and anxiety and all these and psychosis, all these things that we’re we are caring about here, they’re they’re running out of fuel. And the neurons run out of fuel, they could become dysfunctional. They’re not performing their job.

[00:48:35 –> 00:49:05] Dr. Matt Bernstein: They can’t, you know, transmit that signal in the right way. Either they’re gonna become hypofunctional. They’re gonna, you know, start transmitting the signal too slowly or or not as often as they should, or they become hyperexcitable from low energy. Either one can happen, and that would lead to different types of mental health symptoms and and a different type of disorder depending on the individual person. So here come ketone, and they just diffuse right into that cell in those areas, in the in those important areas without needing an insulin signal.

[00:49:05 –> 00:49:23] Dr. Matt Bernstein: So there’s an immediate rescue of an energy problem that’s going on in these really important regions. And there are some people that we see this clinically who really soon after going into ketosis start saying, I feel different. Wow. Like, I can think better. I have someone at the program right now where this is happening, like, as we speak.

[00:49:24 –> 00:49:38] Dr. Matt Bernstein: Like, literally within the first day or two of being in ketosis, she’s talking about having her brain come back online. She can read. She can focus, like, in a way that she couldn’t before. That’s extraordinary. So it’s really cool.

[00:49:38 –> 00:50:01] Dr. Matt Bernstein: Now not everyone gets that experience, and and and maybe that the other mechanisms are more important for them. But as you said, when the brain when when the neurons are using ketones and the and the other cells too, I mean, I don’t think this is exclusive to to neurons. You know? You know, glial cells, astrocytes, you know, same same deal. Less oxidative stress, less inflammation.

[00:50:01 –> 00:50:28] Dr. Matt Bernstein: You were right about what you said about the NRF two pathway getting activated and lowering inflammation. There’s also an increase in brain derived neurotropic factor. So now we’re getting into the signaling molecule aspects of what ketones do. So ketones activate a histone deacetylase that turns on brain drive neurotropic factor transcription. And so more BDNF, a more flexible brain, a brain that can learn.

[00:50:28 –> 00:50:43] Dr. Matt Bernstein: And and what I say to people is that a brain that is flexible and can learn, that’s mental health. Right? That’s the definition of mental health in many ways. Right? When brains become unable to learn and inflexible, that’s when you get all these mental health symptoms.

[00:50:44 –> 00:50:44] Dr. Ravi Kumar: Yeah.

[00:50:44 –> 00:51:12] Dr. Matt Bernstein: And so more BDNF, more learning, more flexibility, that’s amazing. And then there’s this whole other pathway where ketones activate PGC one alpha, which turns on mitochondrial biogenesis and mitophagy. And this is probably, you know, one of the most important things that we that we can imagine. So just back up one second. There’s a whole literature in all these mental health conditions having mitochondrial dysfunction.

[00:51:12 –> 00:51:50] Dr. Matt Bernstein: There’s studies that look at how many dysfunctional mitochondrial proteins there are in brains of people with depression, bipolar, schizophrenia. I think in depression, it’s like 48 dysfunctional mitochondrial proteins, and schizophrenia and bipolar, it’s like over a 100 different dysfunctional mitochondrial proteins. And so we we we and there’s other evidence too. That’s just one line of evidence, but there’s there’s multiple lines of evidence to show that all these serious mental health conditions have mitochondrial dysfunction going on in in neurons and and other cells in the brain. And, you know, mitochondria are the energy factories as we know, but they do way more than that, we’re now realizing.

[00:51:50 –> 00:52:13] Dr. Matt Bernstein: You know, they’re involved in gene transcription in the nucleus. They’re involved in the initiation and resolution of inflammation. They’re involved in the first steps of hormone synthesis. They’re involved they actually huddle around at the end of the of the neuron around the vesicles that are gonna release a neurotransmitter to allow that vesicle of neurotransmitters to be released. And so they’re really controlling neurotransmission in many ways.

[00:52:13 –> 00:53:10] Dr. Matt Bernstein: And so when mitochondria are not numerous enough or they’re dysfunctional, absolutely, we’re gonna have mental health problems from the energy perspective, but from all these other perspectives as well. And if we have an intervention that can signal the cells to make more mitochondria and to recycle the parts of the damaged mitochondria to make new highly functional mitochondria, we’ve got a long term, you know, brain improvement intervention here. And that’s exactly what I see clinically is that the most benefits occur the longer someone stays in ketosis. And I think these signaling mechanisms like the BDNF and the mitochondria mechanism that are more about signaling and more long term are ultimately the even the most important mechanisms, even more important than the different fuel source, which is important. But I think it’s what allows that long term recovery that we see.

[00:53:10 –> 00:53:28] Dr. Matt Bernstein: And what I generally say is that, you know, you’ll feel better in three months, but you’ll feel better at month six than you even do at month three if you keep going. And you’ll feel better at month 12 than you did at month six. And you’ll definitely feel better at month 24 than you did at month 12. The longer you do this, the better you’re going to feel.

[00:53:29 –> 00:53:56] Dr. Ravi Kumar: Yeah. So I it’s that’s really cool because there’s this initial benefit from ketones and from ketogenesis, and then there’s this long term, basically, remodeling of the whole brain metabolic system with long term ketones. Now in in the real world, you know, before advent of agriculture and modern society, ketogenesis didn’t go on for two years. Correct. It You cycled in and out.

[00:53:56 –> 00:54:00] Dr. Ravi Kumar: Right? Is that mean, is that something that people can do and still get the benefits?

[00:54:00 –> 00:54:25] Dr. Matt Bernstein: I think it’s tricky when it comes to, you know, talking about someone with a severe mental health disorder. Okay. We definitely see people who just living in the real world, they do cycle in and out. And some of those people do okay when they’re out of ketosis, but many of them don’t actually, especially in the first year or two. I think it’s risky to cycle out if you’re doing this for a medical condition.

[00:54:25 –> 00:54:55] Dr. Matt Bernstein: Now I think, you know, from the evolutionary perspective and for general health perspective, which is like sort of how I feel like I’m doing it for myself. I’m doing it for my general health and my overall brain health. I’m not shooting for high levels of ketosis, and I will cycle in and out just inadvertently because I’m not keeping my eye on the ball sometimes. But and it doesn’t cause me any kind of major problem when I do that. But for someone who’s doing it for their bipolar or their major depression and their schizophrenia, I wouldn’t recommend cycling in and out, especially in the early stages.

[00:54:55 –> 00:55:22] Dr. Matt Bernstein: Now that being said, I know a few people who have done this for severe mental health who do purposefully cycle out, you know, and they do okay. Even a couple people who are off of their medication, and they can still cycle out and be okay for a period of time. But even those people will absolutely say, oh, yeah. But I feel better, and my brain functions better when I’m in ketosis for sure. So, you know, it just really depends on the individual situation.

[00:55:22 –> 00:55:35] Dr. Matt Bernstein: But I I don’t promise to people that they’ll be able to cycle in and out or that they’ll be able to come off the diet and retain all the benefits. We just don’t have enough data to make those kind of statements at this point. But there are there are individuals where that happens.

[00:55:35 –> 00:55:49] Dr. Ravi Kumar: Okay. And what about this concept? I think you mentioned it earlier in the show where you use ketosis to completely basically remodel the body and the the physiology of the person. I mean, they they lose weight. Their their metabolic health improves.

[00:55:49 –> 00:55:58] Dr. Ravi Kumar: Their neurological health improves. And then after a couple years, they can come off and maybe be normal again. Is that a concept that you still think can Yeah.

[00:55:58 –> 00:56:19] Dr. Matt Bernstein: What I was talking about then was in kids with epilepsy. Okay. So, again, a little different because, you know, a child’s brain is more plastic, obviously, than an adult’s brain. And it’s a different condition. We’re talking about epilepsy versus mental health, and it’s you know, in that literature, it’s really the kids who had the best outcomes were more likely to be able to come off the diet and retain the benefit.

[00:56:19 –> 00:56:34] Dr. Matt Bernstein: So, again, it’s not universal, but even the fact that that’s possible is really intriguing. And, you know, for the people where they do have that outcome, you know, that’s that’s amazing. I just feel like we can’t we can’t entice and promise that for most people at this point.

[00:56:35 –> 00:57:01] Dr. Ravi Kumar: You know, one other thing that I think is potentially out there, maybe more so in kids than adults, is that there are people who have mental health issues who are not metabolically in horrible shape. Right. I mean, I think it’s more common that people who have mental health issues are metabolically unhealthy. I think that’s probably the most likely scenario. But what about these people who are metabolically not bad and they’re still having mental health issues?

[00:57:01 –> 00:57:03] Dr. Ravi Kumar: Is that just a different root cause?

[00:57:04 –> 00:57:19] Dr. Matt Bernstein: Well, yeah, it’s a it’s a great question. And I don’t know the exact answer, but I’ll tell you what I do know to answer that question. I mean, I think it’s a it’s such a good question that I don’t think anyone can really answer that question right now. But this is what we know. For example, a lot of these kids with epilepsy, for example, are are metabolically healthy.

[00:57:19 –> 00:57:58] Dr. Matt Bernstein: They’re young kids. They haven’t gotten into insulin resistance yet, but still this metabolic intervention, you know, really helps their brain. Maybe that’s a little bit of a different mechanism. What I what I will say is that I the idea that these areas of the brain that we talked about before, the hippocampus and the amygdala and the hypothalamus becoming insulin resistant, you know, can happen even when there’s fairly good metabolic health in the rest of the body. And so, you know, different and and I think, you know, that could be partly genetic, partly a stress response that, you know, these are areas of the brain that are more potentially responsive to stress that’s going on.

[00:57:58 –> 00:58:34] Dr. Matt Bernstein: And so, you know, we know that, you know, there’s a lot of connection between adverse childhood events and, you know, childhood traumas and mental health conditions later on. So we know the stress, you know, etiology for mental health is is huge. And so you can sort of put these things together and say, well, maybe it’s the stress and the genetics that’s leading to a metabolic problem in the brain even when the body is not having overt signs of a metabolic problem. Or it’s just that, you know, again, the mitochondria are are not quite the same, and they need a boost. The other way to think about it.

[00:58:34 –> 00:58:55] Dr. Matt Bernstein: Right? And, I don’t think anyone knows the answers to these questions yet, but these are some of the ways that one might conceive of why that is what we actually observe because it is what we observe. I mean, I have people come in who are their lab work shows no signs of peripheral metabolic problems at all. They have no insulin resistance. Their lipid panel looks beautiful.

[00:58:55 –> 00:59:12] Dr. Matt Bernstein: Their hemoglobin a one c is 5.0 or 4.9. You know, they they they don’t have any visceral fat on their body composition scan, and they respond beautifully to this approach. And so why would that be? Right? I mean, that’s you know?

[00:59:12 –> 00:59:33] Dr. Matt Bernstein: So so, you know, so I think we just have to say to ourselves that the metabolic state of the brain can be different than the metabolic state of the rest of the body. Yeah. And why that is, we don’t know. I have all the answers. But at this point, if someone’s coming in with a mental health problem, I almost assume that there’s a metabolic problem going on in their brain even if I can’t measure it in their blood work.

[00:59:34 –> 00:59:48] Dr. Ravi Kumar: Okay. Yeah. That’s very interesting. And, you know, the way I like to look at this particular scenario would be, hey. There’s whether you’re metabolically unhealthy or you’re metabolically healthy and you’re having a problem in your brain, there’s some inflammatory problem going on.

[00:59:48 –> 01:00:13] Dr. Ravi Kumar: It could be from you know, if you’re metabolically you have metabolic syndrome and you’re insulin resistant in your brain, you’re not getting enough energy, the brain’s gonna be inflamed because it’s it’s not getting the energy it needs. It’s creating a lot of oxidative free radicals and whatnot. But what if you’re metabolically healthy but you get an infection, like, you know, kids with PANDAS or PANS? Right. Or you get, you know, I I think infectious etiologies could be huge.

[01:00:13 –> 01:00:43] Dr. Ravi Kumar: A metabolically healthy person, they’re they’re either the immune system’s attacking the brain or there’s a direct infection or indolent infection in the brain. That creates inflammation, and now the brain is because in an inflamed brain, it becomes insulin resistant. So I could see how that could maybe bypass this inflammatory, state in a in a otherwise healthy person. It’s it’s just kind of a cool concept. And, the fact that you’re seeing it work in metabolically healthy people, it kind of tells me that maybe that’s what’s happening.

[01:00:44 –> 01:01:03] Dr. Matt Bernstein: Yeah. I I I think you’re you’re definitely onto something with that line of thinking, and it ties back to, you know, story of that I told about my kids. You know? Absolutely. And and I think what I like about the ketogenic diet, I mean, number one, it being so safe, but it has such a, you know, variety of mechanisms in which it works through.

[01:01:03 –> 01:01:26] Dr. Matt Bernstein: Whether whether it is an inflammatory process or an oxidative stress problem or a mitochondrial problem or an insulin resistance problem, you know, it’s gonna be helpful. And and we didn’t even talk about one other mechanism or a couple other mechanisms actually that they’re from the epilepsy literature. One is that ketogenic diets raise GABA and lower glutamate. And so that’s really interesting, you know, tying back to our neurotransmitter.

[01:01:26 –> 01:01:30] Dr. Ravi Kumar: That a little bit better. So people know what GABA and glutamate actually do and why

[01:01:30 –> 01:01:50] Dr. Matt Bernstein: that’s important. So GABA is a neurotransmitter. It’s not one that we talk about as much as the in psychiatry at least as, you know, things like serotonin and dopamine and norepinephrine. But it’s a different and those neurotransmitters, by the way, are kind of localized to certain parts of the brain. GABA and glutamate are these neurotransmitters that are kind of all throughout the brain.

[01:01:51 –> 01:02:08] Dr. Matt Bernstein: And GABA is the kind of universal brake pedal in the brain. It sort of slows down neurotransmission when GABA is active. And glutamate’s the opposite. It’s sort of like the gas pedal. It’s sort of speeding up and, you know, exciting neurotransmission all throughout the brain when it’s more active.

[01:02:08 –> 01:02:30] Dr. Matt Bernstein: And so for epilepsy, for seizures, it makes a lot of sense. You want more GABA, kind of tamp everything down to, you know, stop those seizures from happening. You want less glutamate. But it turns out in mental health, that’s also pretty relevant. That, we do know that, you know, increasing GABA is helpful for anxiety, for depression, and and maybe for, you know, some of these other, mental health conditions as well.

[01:02:30 –> 01:02:57] Dr. Matt Bernstein: And that too much excitatory glutamate is a big problem, especially in bipolar and schizophrenia. And so those are relevant to mental health. And we know about those from good literature from epilepsy. The other mechanism that we haven’t mentioned yet is there’s there’s clearly a microbiome gut brain access aspect to ketogenic diets in the brain too. You know, there’s been some basic science in epilepsy showing that in mice that you know, they they do these studies in mice where they, you know, remove their microbiome.

[01:02:57 –> 01:03:19] Dr. Matt Bernstein: You know, they they sterilize their guts. You know? It’s a tricky thing to do. The same mice who had seizures who had a sterilized gut didn’t get the response from the ketogenic diet as the mice that had a microbiome. So it showed that you need the microbiome there to actually do something with the ketogenic diet to help seizures, which is fascinating.

[01:03:19 –> 01:03:55] Dr. Matt Bernstein: Right. And they can also see some changes in some of the species, in particular, an increase in the species achromanacea, which is a really important species that people are now paying a lot of attention to in, you know, models with ketogenic diets and seizures that, you know, increase in acromancy was also important for getting the seizure benefit. So, you know, we we don’t know nearly enough about the microbiome to know exactly how it’s working in mental health yet in any respect. But there are studies about even just using probiotics for depression that sometimes show positive results. And we know that the microbiome gut brain axis is incredibly powerful.

[01:03:55 –> 01:04:22] Dr. Matt Bernstein: It’s just that we’re just at the infancy of learning all about it and how to manipulate it in in ways that might be really useful. But it’s certainly one of the mechanisms by which this this diet is helping. And it’s it’s one of the reasons why I really recommend, if possible, that people do a whole foods version of a ketogenic diet. We include lots of fiber and lots of plant material that don’t have a carb you know, glycemic index so that they get a lot of polyphenols. Yeah.

[01:04:22 –> 01:04:43] Dr. Matt Bernstein: Because we know that polyphenols are also good for the gut microbiome. And there’s there’s interesting literature too that show that polyphenols apply some of the same stresses to to cells, including activating PGC one alpha. So so, you know, going on that same mechanism that ketogenic diets improve mitochondrial health, polyphenols seem to do some of the same things.

[01:04:43 –> 01:04:55] Dr. Ravi Kumar: Yeah. That’s I mean, that’s very interesting. The gut microbiome neurological access is just very apparent. I mean, there’s a there’s actually a nerve that goes from your brain straight down to your gut. It’s called the vagus nerve.

[01:04:55 –> 01:04:56] Dr. Matt Bernstein: That’s

[01:04:56 –> 01:05:15] Dr. Ravi Kumar: right. And, you know, you make more serotonin in your gut than you do in your whole neurological access. Right. And, also, gut bacteria actually make ketone bodies. I mean, they metabolize fatty acids into ketone bodies that are released in and feed our enterocytes, which line our gut and are released into our bloodstream.

[01:05:15 –> 01:05:30] Dr. Ravi Kumar: So the whole thing seems very well tied together. Yep. And the other thing that’s very apparent in the literature is that people with mental illness often have very unhealthy microbiomes. That association is is is definitely there. So what about this?

[01:05:30 –> 01:05:43] Dr. Ravi Kumar: What about exogenous ketones? Meaning, taking ketones in in orally as a food source and and having them absorb straight into your bloodstream, can you get the same benefits as a ketogenic diet?

[01:05:43 –> 01:05:55] Dr. Matt Bernstein: Yeah. I mean, my short answer is, unfortunately, no. You can’t get all the same benefits. It’s not that you can’t get some benefits, and people are studying them. They haven’t been studying nearly as much as ketogenic diets.

[01:05:55 –> 01:06:20] Dr. Matt Bernstein: From a practical perspective, it would be fairly expensive to have exogenous ketones all throughout the day to keep the level of ketones up for for that whole period of time. And then they would still go down overnight because, generally, they only last in the bloodstream for about two or three hours when you take an exogenous ketone. So they don’t taste great. It’s not real food. Who knows what it’s doing to our microbiome?

[01:06:20 –> 01:06:52] Dr. Matt Bernstein: And for the people who are not metabolically healthy, you’re not getting all the other benefits that you’d be getting from a ketogenic diet. Right? So for people who are having metabolic issues, which, you know, truthfully is the majority of the people that come in my doors at least because many of them had been on psychiatric medications for many years and have gained weight. They’ve they’ve got problems with their glucose regulation and their lipids, and they have visceral fat. You know, you’re not gonna get all those benefits from taking exogenous ketones that you would get from ketogenic diets or reversing all that metabolic dysfunction in the body.

[01:06:52 –> 01:07:14] Dr. Matt Bernstein: And so, you know, from my perspective, you know, we’re just not there yet with exogenous ketones to use them practically in the clinic. There’s some use cases that make sense to me. Like, if someone wants to try out what it feels like to be in ketosis, you know, they could try it, you know, to see if there’s some kind of an immediate benefit. And and for some people, there might be an immediate benefit, and that might be the the selling point to say, okay. Now I want to do the diet.

[01:07:14 –> 01:07:32] Dr. Matt Bernstein: Right. So that could be an issue. Or if someone really relies on being in ketosis for their mental health and when they come out of it, they really don’t feel well. If they accidentally come out of ketosis, this would be something they could take for a couple days while they’re getting back into ketosis through their diet. So that could be another, you know, really helpful use.

[01:07:32 –> 01:07:56] Dr. Matt Bernstein: Or just for performance, people use them for, you know, athletic performance or, you know, brain health performance. I I’ve tried them out for that use and, you know you know, if I’m giving a a lecture and I’m feeling a little anxious about it, I want my brain to work really well. I’ve taken some exogenous ketones to boost mine my ketone levels even quite a bit higher. And, yeah, it feels it feels really good.

[01:07:57 –> 01:08:08] Dr. Ravi Kumar: Yeah. Okay. So let’s, like, just talk about a little bit about the practical side of this. You’re bringing patients, inpatients, into an inpatient environment. You’re cooking for them.

[01:08:08 –> 01:08:27] Dr. Ravi Kumar: You’re helping them exercise. You’re doing all the things that help motivate a very unmotivated person. And I imagine they’re leaving your facility in a much better place. What about people who don’t have that opportunity? Do you know they’re depressed or they’ve got some mental illness or they have a child or a loved one with this?

[01:08:27 –> 01:08:32] Dr. Ravi Kumar: Yeah. What can they do on their own to facilitate this kind of improvement?

[01:08:34 –> 01:08:57] Dr. Matt Bernstein: Yeah. I mean, it, you know, it depends on what the resources are. Right? I mean, this shouldn’t need to be expensive. I mean, right now, it’s only expensive because there’s very few places that do this, and there’s not a local keto metabolism for mental health coach that you can go to and get all the help that you need, you know, right in your neighborhood.

[01:08:57 –> 01:09:10] Dr. Matt Bernstein: But there should be, in my view. And and hopefully in a few years, that’s the kind of thing that will exist. There are a lot of people who’ve been trained to do this from a clinical perspective. You know, not all of them are psychiatrists. Some of them are psychologists.

[01:09:10 –> 01:09:40] Dr. Matt Bernstein: Some of them are social workers or other kind of master’s level therapists. There’s a lot of dietitians and nutritionists who are really trained in how to do this. And, people can look online on Metabolic Mind, or there’s another, website called Diagnosis Diet run by Dr. Georgia Eid that has both of those sites have directories of clinicians. So people can look online, find people in their area. And, you know, a lot of this can be really done through family support too.

[01:09:40 –> 01:10:04] Dr. Matt Bernstein: So a lot of the functions that we’re providing in our program, you know, could be potentially provided by a really motivated family to get someone to do all this. You know, there does need to be some medical supervision, I would say. I mean, the the prescribing doctor in the scenario needs to be aware of what’s going on. There’s some things to look at from a lab work perspective that are important to follow. We want to follow people’s lipid panel.

[01:10:04 –> 01:10:44] Dr. Matt Bernstein: One key point that I should mention for people who are really interested in doing this is I like to measure carnitine at baseline and after a few months because carnitine is a really important amino acid in for someone who’s doing a ketogenic diet. Carnitine is what gets the fatty acids and ketones into across the inner mitochondrial membrane for use as fuel. And if you don’t have enough carnitine to to run that transporter, you can have all the ketones and fatty acids in the world, but not be able to use those for fuel. And so, you know, that’s really important. Sometimes people become carnitine deficient a few months into the diet, and there’s some medications that make people carnitine deficient.

[01:10:44 –> 01:10:48] Dr. Matt Bernstein: Valproic acid in particular is the worst offender in that regard.

[01:10:48 –> 01:10:49] Dr. Ravi Kumar: Okay.

[01:10:49 –> 01:11:09] Dr. Matt Bernstein: So it’s really important to to measure carnitine. We I measure a lot of other things too. Like, I you know, I measure iron because iron’s actually part of some of those proteins in the electron transport chain as well. And so if someone has an iron deficiency, that could be a part of their energy problem. So, you know, zinc zinc is important.

[01:11:09 –> 01:11:36] Dr. Matt Bernstein: I I wish zinc level zinc levels are easier to get reliable zinc levels, unfortunately. They’re the the labs aren’t so good at giving reliable zinc levels. Mhmm. In any case, the prescriber needs to know because also the medications may need to be adjusted. And so we’re we’re talking about this diet as being safe, but there’s some medical considerations that that need to be thought about, especially if someone’s on a medication like lithium, for example, that has a very narrow therapeutic index.

[01:11:36 –> 01:11:50] Dr. Matt Bernstein: When someone’s going into ketosis, there’s often a bit of a diuresis that happens as the glycogen is being used up and the water from the glycogen is being diuresed, and you, you know, you can you can change lithium levels from that. So we Which

[01:11:50 –> 01:11:51] Dr. Ravi Kumar: means peeing it out, folks.

[01:11:52 –> 01:11:54] Dr. Matt Bernstein: Yes. Exactly. Yeah. Exactly.

[01:11:54 –> 01:11:58] Dr. Ravi Kumar: So you pee out the water that was normally solubilizing the glycogen, and now

[01:11:58 –> 01:12:13] Dr. Matt Bernstein: It’s right. And that changes electrolyte levels too, so we have to, you know, really be careful about repleting electrolytes if someone’s Right. Going to ketosis quickly. So there’s definitely some some nuances to this. I’m not trying to say this is so safe that people can just completely do it themselves at home.

[01:12:13 –> 01:12:37] Dr. Matt Bernstein: Some some medical advice and help is important. But, you know, it doesn’t require expensive medications. It does require a little bit of lab work and some expertise, but it’s just food. And there are studies that show that you can do a ketogenic a whole foods ketogenic diet for with with people on food stamps. And so that’s another complaint sometimes people have is, oh, it’s so expensive to eat that way.

[01:12:38 –> 01:12:56] Dr. Matt Bernstein: And it can be. You can, you know, all get, you know, all grass fed beef and organic, you know, wild caught salmon. And but you can also get, you know, regular old ground beef and cheese and onions and and just make yourself dinner too. And it so it doesn’t absolutely have to be expensive to eat a whole foods ketogenic diet.

[01:12:57 –> 01:13:28] Dr. Ravi Kumar: Yeah. Well, that’s, I think that’s awesome because, you know, even the theoretically, the poorest people in our country who are the least served, the most underserved in the medical community for sure, they could potentially use this as a tool to improve their metabolic health. And, you know, also what you’re talking about doesn’t just have to be used for people with mental health issues. It can be used for anyone who’s metabolically sick, which is unfortunately a large portion of our country and the world. So,

[01:13:28 –> 01:13:44] Dr. Matt Bernstein: yeah, that’s I’m glad you opened that part up because I I agree a 100%. I mean, the the really, really strong literature on ketogenic diets reversing diabetes, type two diabetes, and also that it’s the best Diabetes is curable. Yeah. Curable. Is reversible.

[01:13:44 –> 01:13:52] Dr. Matt Bernstein: Right. Yeah. Yeah. We should say that over and over again because, like, you know, people need to hear that. Like, people think of diabetes, and they say, oh, I’ll be on medications for the rest of my life.

[01:13:52 –> 01:14:08] Dr. Matt Bernstein: It’s just gonna get worse. This is like a a sentence to live a shorter and less healthy life. Completely untrue. Completely untrue. And and yet that’s been the, you know, basically, you know, modus operandi of of the medical field for for many decades now.

[01:14:08 –> 01:14:37] Dr. Matt Bernstein: Yeah. And and the evidence is now very clear that people with type two diabetes can absolutely reverse it. I had someone recently at the program who came in with a hemoglobin a one c up over 10 and got his glucose in such good control of him literally in in two months. And so it wasn’t even the full reduction because hemoglobin and c would measure three months of of glucose control, not two months. But at the end of month two, I think it was already down to, like, 7.4.

[01:14:37 –> 01:15:02] Dr. Matt Bernstein: And triglycerides went from, like, this seven hundreds down to, you know, I think nineties in two months, just eating a ketogenic diet and starting to exercise. So, you know, overall metabolic health, you know, problems are, you know, in some ways, the low hanging fruit here for for the health of our country. There’s so much of it, as you said, and it’s so easy to reverse it with this kind of, intervention.

[01:15:03 –> 01:15:13] Dr. Ravi Kumar: Yeah. Well, that’s fascinating. I think you have brought such a wealth of knowledge to me and my audience. I really appreciate it. Where can people get ahold of you?

[01:15:13 –> 01:15:20] Dr. Ravi Kumar: If they wanna find out more about what you’re doing or, even maybe explore getting someone admitted to your program, how would they do that?

[01:15:20 –> 01:15:45] Dr. Matt Bernstein: So so the program is called Accord, a c c o r d, and the website is accordmh.com. So accordmh.com. That’s the best entry to looking at the program, and there’s a whole education section on there as well. So if people wanna hear more about all of this or there’s some videos of me doing some academic lectures about this. If people wanna hear even more about the science, they can they can go and check that out.

[01:15:45 –> 01:15:57] Dr. Matt Bernstein: And then if people wanna reach me individually, they can find me on LinkedIn. That’s the only social media that I am active on. I’m just not not a social media guy, but I will respond if someone reaches out to me on LinkedIn for sure.

[01:15:57 –> 01:16:04] Dr. Ravi Kumar: Yeah. Okay. Fantastic. Well, I’ll put all those links in the show notes. You know, Dr. Bernstein, thanks so much for joining us.

[01:16:04 –> 01:16:07] Dr. Ravi Kumar: This has been awesome. I I really appreciate it.

[01:16:07 –> 01:16:11] Dr. Matt Bernstein: Thanks for having me. It’s been a great conversation. Okay. Cheers.

[01:16:11 –> 01:16:26] Dr. Ravi Kumar: Okay. So I hope you enjoyed my conversation with Dr. Bernstein. I thought it was a fantastic conversation, but I know there was a lot of information in there. So here’s what I want you to walk away with. Your brain doesn’t run on willpower or good intentions.

[01:16:26 –> 01:17:02] Dr. Ravi Kumar: It runs on energy. And when the cells in your hippocampus, amygdala, and hypothalamus can’t get the fuel that they need, that can show up as anxiety, depression, psychosis, and a dozen other things we’ve been taught to treat purely as chemical problems. And that’s a problem because mainstream medicine just doesn’t understand the connection between mental illness and metabolic health. But there’s a silver lining here. Walking outside in the sunlight, getting your sleep in order, moving your body, and a ketogenic diet can be remarkably effective and doesn’t have to be expensive.

[01:17:02 –> 01:17:30] Dr. Ravi Kumar: Dr. Bernstein made the point that this approach has actually been studied in people on food stamps. So this isn’t a rich person’s intervention. So if you wanna go deeper into the science or you’re considering doing this for yourself or your family members, Dr. Bernstein’s program is called Accord, and you can find him at accordmh.com. I’ll put the link in the show notes along with a link to where to find him on LinkedIn. So I hope this episode helped you.

[01:17:30 –> 01:17:40] Dr. Ravi Kumar: If you think this is valuable information or could be valuable to someone you know, please send it on to them. And until next time, stay curious, stay skeptical, and stay healthy. Cheers.