What follows is a transcript for the podcast Mental Health - Dr. Christopher Palmer - Neuroscience.
Topics within the interview include the following:
- The case for mental disorders really being a metabolic disorder of the brain
- The link between mitochondrial function and mental health
- COVIDs impact on both mitochondrial function and brain health
- Environmental and dietary impacts on mental health
- How fasting heals the body and brain
- The role of the gut-brain connection in mental health
- A whole systems approach to mental illness
Dr. Dan Stickler: Welcome to the Collective Insights Podcast. I'm Dr. Dan Stickler. I'm going to be your host for this episode, and I have a guest that I'm excited to have the conversation with. We have on the podcast today, Dr. Chris Palmer. He's a board certified psychiatrist and assistant professor of psychiatry at Harvard Medical School. Dr. Palmer is the author of Brain Energy, A Revolutionary Breakthrough in Understanding Mental Health and Improving Treatment for Anxiety, Depression, OCD, PTSD and More. A lot of acronyms there. Welcome to the show, Chris.
Dr. Chris Palmer: Thank you, Dan, for having me.
Dr. Dan Stickler: I've been excited to have you on when they told me you were scheduled because typically I don't deal with a lot of mental health issues in my practice. I'm more of a performance and complexity kind of practice that works on optimizing function and everything like that. But it seems like recently I've come across quite a bit of the psychiatric issues, a lot of it PTSD. So we've been working with PTSD in the retired military population. My wife's 30 years retired colonel from the Air Force, and that was an area that she was very passionate about. And so this conversation seems to be right up my alley because I love the approach that you take with this. And in your new book, Brain Energy, you dive deep into the intimate relationship between mental health and nutrition, gut brain connection. Can you talk a little bit about what led you to focusing on the science to support mental disorders being really a metabolic disorder of the brain?
The Case for Why Mental Disorders Are Really a Metabolic Disorder of the Brain
Dr. Chris Palmer: Yeah, so I'm an academic psychiatrist. I've been at Harvard for over 27 years now. And we in the mental health field have been extraordinarily frustrated with our lack of progress in the mental health field. The reality is we have not had significant blockbuster breakthroughs in treatments in decades, actually, and it all revolves around one fundamental issue, which is this basic common sense question, "What exactly causes mental illness?" And largely it has been considered an overwhelmingly complex puzzle because it's the brain, and the brain is extraordinarily complicated and nobody can figure it out.
And researchers are doing their best, and everybody's doing their best, but it's just a never ending complex puzzle, and we're a long, long way away from figuring it out. What we do know are risk factors for mental illness, and those get lumped into the biopsychosocial model, biological, psychological, social factors, neurotransmitters, hormones, genetics, trauma, stress, substance use. Those things all seem to come together and play a role in different people.
How do they fit together? No one knows. I kind of came to this scientific question with all of that in mind. I already knew all of the basics. I knew the existing research. I knew the complexity of the puzzle. And if you had asked me 10 years ago, actually one of my patients asked me 10 years ago, do you think they'll ever figure this out in our lifetime? And I was very clear and firm with him. No, nobody will know what causes mental illness before we die. This is just an overwhelming, complicated problem. The brain is so complex. There's no way anybody is going to do anything to figure this out.
And the thing that set me on the path to propose an audacious theory that mental disorders are metabolic disorders was when I helped one of my longstanding patients with schizoaffective disorder lose weight using a ketogenic diet. And the quick version of the story is that within months his chronic auditory hallucinations and delusions were going away. His symptoms got pretty close to remission. They never reached a hundred percent remission, but they got probably 90 to 95% remission. He was able to do things he hadn't been able to do since the time of his diagnosis. And that set me on a journey not only to start using the ketogenic diet as a treatment for other patients with chronic serious mental disorders and subsequently seeing many other patients achieve full remission of illness with this diet.
I could have stopped there. And the reality is we for people who are hearing this, just want to be mindful, your listeners are probably thinking, "Oh, my God, I'm going to turn this off because this is all quackery." So just take a step back from that. Ketogenic diet, believe it or not, is an evidence-based treatment for epilepsy, a 100 year old evidence-based treatment. It can stop seizures even when medications don't. So we've got a tremendous amount of neuroscience literature on the ketogenic diet and exactly how and why it might play a role in mental illness. We now have six controlled trials underway of ketogenic diet for serious mental illness. We have additional trials for alcoholism, post-traumatic stress disorder, Alzheimer's disease, and other diagnoses. So that field is rapidly taking off, and leading psychiatrists and neuroscientists from around the world are extraordinarily excited and passionate about pursuing it all based on science. But I didn't stop there. I was dumbfounded by the fact that I was putting schizophrenia into remission.
And although I could have said, well, this diet thing seems to be working, I recognized wait, this is a golden opportunity to potentially better understand mental illness because it flies in the face of everything that I've been taught, everything that I've experienced as a clinician. All of our other treatments for the most part aren't putting schizophrenia into remission. The medications usually aren't. Electroconvulsive therapy can be a really powerful short-term treatment, but it doesn't restore lives and health. It's not for people with these chronic debilitating disorders. And so I went on a deep dive with that question. What can I learn about what this diet is doing to the brain in order to better understand the nature of mental illness? And ultimately that's how I arrived at the conclusion. And I'll stop so you can get a word in edgewise.
Dr. Dan Stickler: I love this because... And correct me if I'm wrong on this, but wasn't there an institution back in the seventies, it may might have been the sixties, where they were housing a bunch of schizophrenics and they put them on a carbohydrate restricted diet, and a large portion of them actually improved dramatically. I mean, this was a long time ago.
Dr. Chris Palmer: Yeah. In 1965, there was a study of at least 10 schizophrenic women published in the American Journal of Psychiatry showing that it helped. Fascinatingly, in Russia, they have been using fasting, water fasting, for up to 30 days as a treatment for serious mental illness. And they've been using that since the 1940s. And there are reports that tens of thousands of people have experienced at least short-term reduction or remission of symptoms. The challenge with the Russians is that after a 30 day fast, they put them on a regular diet, and usually the symptoms come right back. So it's a good short-term intervention, but it's not a good long-term intervention.
Dr. Dan Stickler: I have another example I want to mention too is I was a gastric bypass surgeon for a number of years. Back in, it was probably 20 years ago, I had a patient. She was about a year out, and she came in and she had these weird symptoms. She had these migrating limb movements that each day there would be a different limb that she couldn't control. I called psychiatry in, and they came and saw her and they diagnosed her as a conversion disorder. And then somehow I found something about thiamine deficiency, and we gave her a bag of thiamine, and it completely resolved. I mean, metabolic process right there.
Dr. Chris Palmer: That's heartbreaking to hear. I'm going to laugh because it's so ridiculous and ludicrous, but it's kind of heartbreaking to hear. So that was a clear example. This woman had a biological problem. She was probably tormented by her symptoms. Her limbs are just moving erratically. She can't help it. And then we've got the mental health professionals saying, "This is all in your head, lady, just snap out of it. Take some deep breaths, maybe that'll help fix you up." And, of course, taking deep breaths is not going to control a thiamine deficiency. She's got a biological nutritional deficiency, has a really easy treatment plan. And I think the heartbreaking thing in my mind is there are tens of millions of people who could be getting better with other metabolic treatment plans, and we are telling them that this is just in your head or this is just a diagnosis you have to accept. It's a lifelong fate. Your life is basically ruined. We're really sorry. We just don't know any better. We don't know how to help you. Good luck.
Dr. Dan Stickler: Right. I stepped away from the mainstream medicine about 12 or 13 years ago just because I was so frustrated with this in all areas of medicine, internal medicine and surgery and the fact that everything comes down to lifestyle aspects that can be manipulated in some way. But you mentioned something about this being a complex process, and the thing I've really paid attention to is that medicine, ever since the germ theory came aboard, we shifted into a more complicated thinking using algorithms and using this cause and effect piece. And yet when you look at the human system, you're looking at a complex adaptive system. And to address a complex adaptive system, you have to use complexity thinking where there is not going to be a root cause of anything. You've got to look at all of the different inputs that can influence the system, and even the butterfly effect where a small perturbation in one of the nodes can create this massive disruption in the overall system. So was that kind of the conclusion you came to when you started diving into this?
Mitochondrial Function & Mental Health
Dr. Chris Palmer: Yes. The transformation for me was the ketogenic diet and its effects on the brain ultimately led me to these tiny things in our cells called mitochondria. And that led me to do this deep dive into the science of mitochondria. And although most people don't know it, a lot of people know mitochondria as the powerhouse of the cell, and they kind of imagine these things as fairly simplistic little powerhouses just churning out ATP, and they don't do much more than that. And up until about 25 years ago or so, that is largely what the scientific community thought of them. Your teacher who taught you that way back in school wasn't incorrect. That is what they thought. That definition, that simplistic model of what mitochondria are and what they're doing has been completely shattered and disrupted. Cutting edge, groundbreaking research published in the best journals on the planet, nature, cell, all of the medical journals, best journals we have suggest that mitochondria are so much more than powerhouses. Yes, they are powerhouses, but they are doing so much more.
In fact, as I did this deep dive into the science of mitochondria, I began to connect all of the risk factors of mental illness. And so we can start to think about neurotransmitter imbalances, hormonal imbalances, inflammation, epigenetics, all sorts of things. And then when you ask the big picture question, "Well, what exactly could disrupt mitochondrial function or what could play a role in that?" It's exactly what you said, it becomes multifactorial. There's usually not just one thing. There can be multiple things that can contribute to the problem. The good news is that these aren't shocking earth shattering revolutionary things that you've never heard of. These aren't proprietary substances and molecules that you need to get access to or you need to get special permission or you need to have a lot of money to buy. These are common sense lifestyle factors like diet, exercise, sleep, stress, substance use, all of those types of things that can all come together to disrupt what I would call mitochondrial function or we might phrase that to disrupt human metabolism.
And when that disruption occurs in brain cells, it makes those brain cells malfunction, and that malfunction of brain cells results in symptoms that we call mental illness.
COVIDs Impact on Both Mitochondrial Function and Brain Health
Dr. Dan Stickler: I noticed a recent study that was talking about how the spike protein tends to accumulate in mitochondria from COVID. Have you noticed any impact of that with mental health?
Dr. Chris Palmer: Oh, absolutely. For people who get an acute infection with COVID, the standard symptoms of any viral infection, especially if it comes with flu or high levels of inflammation, almost everyone has mental symptoms, meaning they develop fatigue. They might have brain fog, they might lack motivation. Those are actually all hardwired into the human brain. So when we are sick, some scientists have labeled it conservation withdrawal behaviors. It means that when you're sick with the flu or COVID, you want to climb into bed, hide from the world and recuperate, and that is all good. It keeps you out of harm's way. You're weak and vulnerable when you're sick, and your body needs to allocate resources to healing and fighting off the virus, and so that's what we do.
But those are absolutely mental symptoms. The much bigger problem are people who develop long COVID. So the hallmark symptoms of long COVID can include lung symptoms. So some people develop a chronic cough or shortness of breath, but really the most detrimental hallmark symptoms are mental symptoms, fatigue, lack of motivation, brain fog. Some people develop chronic depression, anxiety disorders, and, in fact, some case reports have been published in the medical literature of psychosis, new onset psychosis from COVID or long COVID. So no question infections can play a role in human metabolism and mitochondrial function. They can disrupt mitochondrial function, and that can result in brain symptoms.
Dr. Dan Stickler: And we see quite a bit, I like the way you frame that though, of these mental health issues being poor sleep and brain fog because I think a lot of people when they hear mental health, they're thinking of schizophrenia, OCD, the true diagnostic criteria that are used there. But we've seen a lot of the impact of COVID on the brain in our practice. We do EEGs on all of our clients every year, and we saw significant changes in a lot of them. Even my wife, when she got it, she was having trouble finding words. She's brilliant, and she couldn't identify words for a couple weeks. And finally we mapped her brain again and her peak alpha had dropped from 11 to about nine and a half pre to post COVID. So we did the neuromodulation with her, and we also did plasma apheresis, which has been an amazing intervention for recovering a lot of the mental health aspects post COVID. Do you have any explanation as to what you might think is going on with the apheresis in removing the leader of plasma and just diluting it?
Dr. Chris Palmer: I actually don't. It's not a treatment that I'm all that familiar with, so I haven't done a deep dive into the science of apheresis and how it might be playing a role. There is no doubt in my mind I'm going to assume that somehow it might be helping the body fight off the infection or at least reduce inflammation and anything-
Dr. Dan Stickler: It definitely drops the inflammatory markers. But I think I read a study that they were talking about that are circulating antibodies to CNS tissue that they're finding in the serum. And by reducing that, that's the theory that they were working on in saying that it was improving these auto antibodies that were present from it. But that's a small study, but the studies on apheresis for COVID long haul they've been pretty good.
Dr. Chris Palmer: Awesome.
Dr. Dan Stickler: One of the things I wanted to ask you about is you talked a little bit about genetics, and I'm a founder of a genetics company, and not only do we comb the research, but after we do that, we kind of clinically vet it with our clients to see if what we're seeing is truly the case. And one of the ones we found was GAD1 variants in the genetics. And when people had very low activity of the GAD1, they tended to have a significant issue with anxiety with rumination when they try to sleep, just kind of overactive brains when they were consuming more simple carbohydrates. Is that an area you can speak on?
Dr. Chris Palmer: It's not I, okay. I don't know GAD1. So, again, I would have to do a little bit of a deep dive into the science of that one.
Dr. Dan Stickler: Well, the theory is that it's the conversion of glutamate to GABA, and lower activities result in a higher glutamate content in the brain.
Dr. Chris Palmer: So that kind of goes along with a very long standing paradigm for hyperexcitability in the brain, this glutamate, the GABA imbalance. So either too much glutamate, too much glutamate activity or not enough GABA activity, and that results in what we call hyperexcitability of brain cells and brain circuits. And that hyperexcitability stimulates experiences that people shouldn't be having. So anxiety is one, seizures are an extreme version of that, but hyperexcitability of brain circuits has actually been found in numerous disorders including Alzheimer's disease, schizophrenia, bipolar disorder, chronic depression, post-traumatic stress disorder, on and on. And one of the reasons I'm particularly excited about the metabolic theory of mental illness is that we can begin to understand that. So, yes, there are people who might have a genetic predisposition to higher or lower levels of specific neurotransmitters, and that might be playing a role in that excitability for those people.
But for the majority of people with these diagnoses, I don't think it's a rare genetic thing. I think that it's these lifestyle factors coming together to disrupt brain metabolism, which then results in cells being underactive or overactive, which can then result in symptoms of mental illness. But absolutely, we know DSC1 is a high risk gene. It's largely known as being a high risk gene for schizophrenia, but also confers risk for bipolar disorder and depression and epilepsy and some other diagnoses. So, again, we kind of see this theme of there's an awful lot of overlap between these mental disorders. They're not as unique as we might think, and they're really about this big picture of brain's malfunctioning, parts of the brain being underactive or overactive, and that resulting in dysfunction of the brain.
Dr. Dan Stickler: What's your theory on evolutionary mismatches where we've been moving around so much at such great speeds, I think we've gotten ahead of the ability of the adaptation of the gene expressions to be ideal for these new environments that we're experiencing. Do you think that plays a role in any of this?
Environmental and Dietary Impacts on Mental Health
Dr. Chris Palmer: Absolutely. I think that our environment at large has changed dramatically, although one way to think about it is there's an evolutionary mismatch. I actually think about it a little bit differently. I don't think of it that way. I think of it as our current environment is becoming increasingly toxic. And it is in the same way that we kind of sort of maybe have an environmental crisis. We are also having a human health crisis, but our environment really is written very large. It includes changes in the food supply or things that we call food. Things that we called food a hundred years ago, and things that we call food now are extraordinarily different from each other. The quote/unquote food today has lots and lots of chemicals and artificial ingredients. And, yes, I get it. We call that food today. But in reality, some people will say it's an evolutionary mismatch, but I would rephrase it and just say, no, we're producing something that really is not food.
We're producing something that we should think of as toxic chemicals or addictive substances or substances that disrupt metabolism. And that although they make delicious tasting things at products that we just can't eat one of, they actually might in fact be harmful to human health. And so the solution, the reason I like that phrasing of it or that framing of it as opposed to evolutionary mismatch, evolutionary mismatch almost suggests we need to wait for evolution to catch up. And instead, I would say we just need to get rid of this toxic crap and go back to things that we were actually meant to eat and consume as food. But I would say the environment includes much more than food. It includes all of the chemicals that are accumulating in our water supply, in our lawns, everywhere, and those chemicals are accumulating in the human body, and we really don't fully understand their effects.
But we've got an awful lot of preliminary research suggesting they are harmful to mitochondria and mitochondrial function, that they are endocrine disruptors. I know a lot of people think like, "Oh, that's that paranoid conspiracy. You must be one of those functional medicine quacks when you say endocrine disruptor." Well, guess what? Go on the United States government EPA website. Right there, they acknowledge there are chemicals that are endocrine disruptors. They are changing the hormonal systems in the human body. And guess what plays a role in hormonal production? That would be mitochondria. And so more than likely, these chemicals are disrupting mitochondrial function. That results in imbalances in hormones, and that is playing a profound role on human health.
And we've got screens in front of us humans, whether you like to think of us this way or not, we are animals just like your pets. If any of you've got a pet, if you've got a pet dog, your pet dog is not supposed to be restrained in a chair staring at a screen all day. Your pet dog wants to run around, play, come and play with you, come and play with other living organisms. They want to chase squirrels, they want to chase rabbits. They want to look out the window, they want to go for a run. They want to be out in the sun. That is what we humans are actually supposed to also want to do kind of sort of. I'm not saying we're dogs. I'm not saying we don't have more intelligence. I'm not saying we don't have more meaning and purpose and spirituality and religion and all of that, I'm not saying that, but we do. We are animals and we are meant to be with each other, and we are meant to be around each other and hug each other and play with each other and go out in the sun and run and do things, be productive.
And increasingly, our society is built on systems that prevent that or disrupt that. We're all expected to stare at a screen. And as part of our jobs, kids and schools are expected to stare at screens and do their work on screens. And when they're not doing work on screens, they pull out their phones and then they're doing something on their phones, another screen, as opposed to going out and running and playing or talking to other people or hugging people or whatever. So a lot of problems with our environment, unfortunately,
Dr. Dan Stickler: As we sit here on a screen doing a podcast. So for the people absolutely listening, put it on the headphones, go out and play outside while you're listening to it.
Dr. Chris Palmer: Yes, go for a walk in the sun or in the rain, whatever, it doesn't matter. Go for a walk while you're listening to us talk.
How Fasting Heals the Body and Brain
Dr. Dan Stickler: I want to expand on the ketogenic diet a little bit more. What are you kind of postulating as the mechanism that's occurring with this? And I know it's multifactorial, but why would it be? And we did talk about evolutionary mismatch and that. Why would it be that we would have this risks that would require or that would more suggest that that ketogenic diet would be a more normalized dietary pattern?
Dr. Chris Palmer: The ketogenic diet is actually, if you're doing the medical version of it, the ketogenic diet is actually trying to mimic the fasting state. So you're actually trying to trick the body into thinking that it's actually going without food and fasting interestingly. So fasting is not a healthy diet or a good diet. Fasting is no diet. It is no food. It is going without food. And fasting has been used for millennia in every culture and every religion on the planet for healing, for religious expression, but mostly for healing. I don't think that's a coincidence. I don't think it's a coincidence that fasting somehow found its way into essentially every culture and every religion.
I think fasting really heals the body. It allows the body to repair itself. So again, I'm not arguing that it's the healthy diet. I'm arguing it is a metabolic, it is a healing intervention. I would argue it's a metabolic intervention. It shifts metabolism in profound ways that have tremendous benefits. The problem with fasting is you can only do it for so long and then you starve to death. And that's not very good. So somebody, a physician invented or developed the ketogenic diet to see maybe if we trick the body into thinking it's fasting, but give it enough nutrition, it won't starve, but will get the benefits of fasting. So we actually have a tremendous amount of neuroscience, and as you said, there are numerous mechanisms of action. They include things like ketogenic diet changes, neurotransmitter systems in the brain. It decreases brain inflammation and body inflammation, changes gene expression, it improves insulin signaling, it reduces insulin resistance, it changes the gut microbiome in beneficial ways.
There are some researchers publishing in renowned journals that they think that is the primary mechanism of action, and then that gets into the gut brain connection. So there are all of these different kind of mechanisms of action. The two that I am most excited about and that I ended up honing in on are that the ketogenic diet have powerful effects on mitochondria. And it has these effects in two ways. It stimulates a process called mitophagy, which is getting rid of old and defective mitochondria and replacing them with new ones. And it also stimulates a process called mitochondrial biogenesis or the production of new mitochondria so that when people do a ketogenic diet for a prolonged period of time, this doesn't happen overnight, this can take months or even years. But when people do the ketogenic diet for a prolonged period of time, many of the cells in their body and brain will have more mitochondria, and those mitochondria will be healthier. I believe that is the magic of the ketogenic diet, that these mitochondrial improvements and adaptations can heal metabolically compromised cells and allow those cells to begin functioning normally again.
The Role of Gut-Brain Connection In Mental Health
Dr. Dan Stickler: I love how you kind of tied all different processes in there, especially the gut microbiome, seeing such intense focus now on gut microbiome and mental health. In fact, there was a summit recently on the microbiome and mental health. It was a whole summit on that topic. Can you talk a little bit about what's currently showing with the microbiome and mental health?
Dr. Chris Palmer: In the same way that the microbiome plays a powerful role in metabolic health as well, so microbiome we know plays a role in obesity, diabetes, cardiovascular disease, it also plays a powerful role in brain health. And so this includes many numerous mental diagnoses, mental health diagnoses, all the way from depression and anxiety to autism spectrum disorder, to schizophrenia, bipolar disorder and others, but also disorders that we call neurological such as Parkinson's disease and Alzheimer's disease, so wide ranging effects.
The gut, it gets really complicated really fast. That's the problem. So you'll see people who are going to sell you a probiotic, and this one probiotic is supposed to fix everything that ails you. And unfortunately, it's not that simple, folks. Now, if that one probiotic heals you, all the power to you, all the power to that probiotic company. I'm a hundred percent in favor of people finding answers, and if it's a simple answer, that's great, but unfortunately, we've got thousands and thousands of different microbial species in our guts.
Those microbial species are responding to our diet. And so right there, we have two huge variables that can be wildly different in different people. What are they eating? So what are they putting into their digestive tract for those bacteria to consume? And what bacteria exists there right now? What is the balance of good and bad bacteria or different species of bacteria or whatever? What is the balance or what are the numbers, and how does that have an impact? So bottom line, we know that the bacteria get first dibs on all the food you eat, and they are turning some of that food into other molecules. So short chain fatty acids are the easy one that most people have heard of. The bacteria in your gut will take fiber from fruits and vegetables and turn it into short chain fatty acids, which are good for gut health.
They actually serve as a fuel for the mitochondria in your gut cells. That's what they're doing. That's how they're improving gut health is by helping the mitochondria in the cells that line your gut. So there's that whole complicated thing, but it gets even more complicated. The gut has its own nervous system, and actually 90-95% of the serotonin in the human body is found in the digestive tract. So everybody's heard, oh, serotonin, that's depression, right? Well, guess what? 90 to 95% of it's in your gut. So that starts to call the question, does depression exist in our brain or does it exist in our gut and travel up to our brain? What's going on there? And right now, we don't have it worked out, but given that 90-95% of the serotonin is in the gut, we really need to pay a lot more attention to the gut brain connection when we are trying to understand how does something like Prozac work.
And then, finally, these cells lining the gut, many of them are actually endocrine cells, meaning that they are secreting hormones that travel through the bloodstream. Some of them make it up to the brain and influence brain function. And so the gut-brain connection sounds simple, but it's extraordinarily complicated. It's like a little universe unto itself with so many different variables. And although it's all complicated, I believe, the solutions are common sense. Eat real whole food. Let's look for signs of inflammation in the gut and address them.
It's not rocket science folks. There are scientists trying to unravel this extraordinarily complicated puzzle. They're probably decades, if not centuries away, from doing so. But we don't have to wait for them to figure all of that out. We just need to go back to the basics and eat real whole foods and stuff like that, and we can help people improve their health.
Dr. Dan Stickler: Maybe AI can accelerate the process for us, for sure.
Dr. Chris Palmer: Hopefully. ChatGPT, get on the job.
Dr. Dan Stickler: That's right. Do your work. I love that you just showed the profound complexity. I mean, people look at the brain and they're like, oh, my god, it's just too complex. You look at the gut microbiome and you say, oh, my God, it's just too complex. And then you look at the gut brain connection and it's like, oh, my God, it's just too complex. You've got all of these things playing. And for people to think that there is one intervention that's going to change something, it's just insane. And knowing that we are a biologic organism that can be treated ourselves the way that we were intended to be living through these lifestyle factors through nutrition, through sleep, people are just looking for that one thing that's going to change it, and it's hard to get people to understand that it's all of this stuff. It's not just this... I mean, it's even the community that you have, it's the relationships that you have with people.
All of these have an impact on all of these areas. It's not just, oh, we need to increase serotonin or something like that. And that's what we've been focused on for so many years in medicine is finding that one thing that's going to change it. And I think for me, I would love to talk a little bit about the emergence of psychedelics in this space if you're open to that. Because it is, like you said, I mean psychiatry, and I think most of medicine in general, if you look at the last 50 years, what we anticipated where we would be at this point 50 years ago, I mean, we predicted a lot of the stuff from technology, from travel and all that, but the predictions from medicine fell way short. We haven't had anything that impressive. I think the most impressive thing in the past 10 years has been the GLP1 receptor agonists, the semaglutide, tirzepatide.
And now it's turning out that those even, they're appetite suppressants, they're insulin sensitizers, but they're actually having effects in the brain too. I mean, there are direct effects of the GLP1 agonists in the brain, and these are coming from the gut, so this is fascinating. And now with the psychedelics, we're seeing a whole new world open up and giving new perspectives on things. I think I read the other day about ketamine and the antidepressant effect, and they've been trying to identify what it is that's actually creating all of this. And there was one person that postulated ketamine is actually an antibiotic, and it actually kills off certain bacteria in the gut that had been shown to be detrimental in causing one of the contributors to depression. And so I'm looking at this and going, oh, my God. I mean, there's just so many pieces to this puzzle. Where do we start?
A Whole Systems Approach to Mental Health
Dr. Chris Palmer: Yeah, on one hand, when you think about the science of it, it's overwhelming. It's complex. It's hard. I'm going to tell you though as a clinician, I treat treatment resistant illnesses. I don't treat bread and butter depression and anxiety. I treat the people who have tried dozens and dozens of medicines, who have been in psychotherapy for decades, who have tried electroconvulsive therapy and TMS and even ketamine, injections and other things, and nothing has worked. And the message I am here to share with all of you is common sense lifestyle strategies sometimes more sophisticated ones like the ketogenic diet.
The ketogenic diet to most people is not common sense. Some people think it's a dangerous diet. Some people think, "Why would anyone eat that way? That can't be good for you." So that's where I look at the complexity of the science to understand, well, wait, no, this is a unique treatment that has a role for some people because this is really powerful. But implementing the ketogenic diet is not rocket science. I'm not saying it's easy, but it's not rocket science. You can do it. Lots of people do it. Lots of children with epilepsy do it. Lots of people losing weight do it. Others can do it as well. And when we pair some of these lifestyle interventions; diet, exercise, sleep, getting rid of harmful substances, maybe getting people off of toxic medications that are not helping their metabolism, that if we look at all of those things and slowly but surely implement one after another, I truly believe we can heal people.
And I believe that not based on some fairytale fantasy. I'm not trying to offer false hope. I am seeing it in hundreds of people. We've got people coming out of the woodwork wanting to share their stories of how they used to have schizophrenia and they don't anymore. How they used to have drug addiction and they don't anymore. And they overcame it in using these strategies, and they want to share their stories because they were trapped in hell, and they were being told, we don't know what's wrong with you. It's the brain. It's the gut brain connection. It's also complicated. We don't have a pill for you. We're really sorry. We'll just keep trying all these other pills, but none of them are working. And then they found their way to health using basic common sense strategies.
Easiest example if I can share with you, just in case anybody's really not getting this. We grow plants on this planet earth. There are people called farmers and gardeners, and they grow plants. When a plant isn't growing, what pill do you give it? Well, you don't give it a pill. You assess its environment, you assess its basic needs, and you give it its basic needs. Now does that mean the plant needs more water? No, not necessarily. It might need less water. Does the plant need more sunlight? Well, maybe, but maybe it needs less sunlight. Does it need more fertilizer? Maybe. Maybe it needs less fertilizer. Right there, gosh, that's complicated. More fertilizer or less fertilizer? More sunlight or less sunlight? More water or less water? Dr. Palmer, tell us which one it is.
Guess what? Even though it's complicated, and I can't tell you which one it is, for every plant on the planet, we got billions of people who know how to grow plants. And plants are growing, and they're thriving, and they're doing well, even though it's a little complicated and we don't have a one size fits all solution for all the plants. It's not that hard to figure out. And what I'm here to tell you is human health is not that much different. Yes, humans are more complicated than plants. So, yes, we might need some meaning and purpose in our lives. We might need to resolve conflicts with people who care about us. We might need to figure out what is in this food that we're eating that's supposed to be food. Is it really food or is it some kind of a mitochondrial toxin? So maybe we've got a little more complexity to figure out, but it's not that all that complicated. We can do it using common sense lifestyle strategies.
Dr. Dan Stickler: You forgot about glyphosate deficiency too that you got over-
Dr. Chris Palmer: I'm with you, I'm with you. We want to understand the effects of glyphosate as well.
Dr. Dan Stickler: So to close out here, I think it's important that we clarify the ketogenic diet because there are so many versions of it out there. I see people walking around just eating bags of pork rinds thinking they're eating the ketogenic diet or they'll buy these chocolate bars that are keto approved and everything like that. So let's talk the basics of the ketogenic diet.
Defining the Ketogenic Diet
Dr. Chris Palmer: You are absolutely correct. There are numerous variations of the ketogenic diet, and on one hand that can be problematic because of the examples you just gave. There are some versions that people think are ketogenic diets and maybe they're not the healthiest version, and maybe they're even harmful versions of a diet. The good news is there are lots of versions of the ketogenic diet and people can often find one that suits their needs and preferences. So there are vegan ketogenic diets, there are vegetarian versions, omnivore versions, carnivore versions, all sorts of versions. The bottom line is really simple. A ketogenic diet has one definitive biomarker. You're either producing ketones or you're not. And you're producing ketones at a certain level or not depending on what diagnosis you're trying to treat. You might want different levels. Some people think the levels don't matter at all. I personally professionally think the levels really do matter, but there's a biomarker.
We can use urine strips or a blood monitor, and we can see how much ketones does someone have, and that can guide the dietary intervention. The rules of thumb that I will give, what is your general recommendation for a ketogenic diet? Number one, achieve ketosis. Test urine or test your blood, make sure you've got ketones, because if you don't have ketones, you're definitely not on a ketogenic diet, so you need to have reasonably higher than normal ketones. Number two, eat real whole food. Real food, whole food. Don't eat stuff like the Keto Delicious Chocolate Bars that you can buy at Costco or Walmart. Don't eat those. If you really need to eat them, go ahead. Maybe have them every now and then if that's what you really have to do or need to do in order to satisfy a sweet tooth. But for the most part, if you read the ingredient list, they've got lots of chemicals in them.
And so I'm going with this common sense approach that if you're using a ketogenic diet, you're probably doing it because you've got a health problem. You weight too much or you've got diabetes or you've got a mental health challenge or epilepsy or something, something's wrong. So let's give your body tender loving care just like we would a plant that's not growing well or that's not thriving and we are going to pamper it. We are going to give it some fresh soil and try to give it a lot of sunlight and water. We're going to do the same thing with diet. Real whole foods. Avoid things that are highly processed with lots of chemicals, and that's it. I mean, as a rule of thumb, I tend to go more omnivore. So meat, fish, poultry, lots of protein sources. You've got to have fat sources with that. So that might be fatty cuts of meat or salmon, fatty fish. It might be nuts, avocados, olive oil. And then at least some low carbohydrate vegetables; salads, spinach, asparagus, broccoli, cauliflower, those types of things. That would be the all-purpose general ketogenic diet that I would recommend.
Dr. Dan Stickler: Yeah, we've had very good success using the Mediterranean ketogenic diet, and that's got some pretty profound epigenetic influence from it. Two questions. One, what's your thoughts on the BHB, the ketone esters to assist with ketosis?
Dr. Chris Palmer: So as a rule of thumb, there is research going on to see what role exogenous ketones might play. It would obviously be a lot easier to do whatever diet you want, lots of carbohydrates. You don't have to change your diet at all, and you just drink a bottle of ketones. Unfortunately, the data that I have seen so far and the clinical work that I have done suggests that exogenous ketones do not give you the same effects or benefits of the full on ketogenic diet. Now, that's not to say they don't give you some benefits. I think they do give some benefits. Some people notice some improvement in some symptoms. But I've had patients with bipolar disorder, schizophrenia, who were doing extraordinarily well on a ketogenic diet. They tried to transition off the diet and just drink ketones every day, and that did not do much at all for their serious mental symptoms.
And we don't have any evidence in humans that exogenous ketones can stop seizures even though the ketogenic diet can definitely stop seizures. And to the best of my knowledge, we don't even have one case report of anybody using exogenous ketones to control their epilepsy. So the diet is doing a lot more than just producing ketones. It's changing the gut microbiome, it's changing insulin levels and all sorts of other things in addition to producing ketones.
Dr. Dan Stickler: Yeah, thank you for that. My final question, what if you have someone who's carrying an APOE4 allele? What's your thoughts on the ketogenic diet with that?
Dr. Chris Palmer: Right now, we've got a couple of preliminary studies showing that the ketogenic diet in people who actually have full-blown Alzheimer's disease already may in fact be one of the most powerful treatments we have available today. They were small pilot trials. I will be the first to say that. Small pilot trials. They need to be replicated, they need to be in larger samples, and we need longer term data. We need to see what happens, not over 12 weeks, but what happens over one year or five years. But the pilot data is extraordinarily promising in a way that medication trials for Alzheimer's disease have never been. The ketogenic diet not only is reducing biomarkers of Alzheimer's disease, reducing brain inflammation, improving brain metabolism, but it's also reducing symptoms. People are getting improved quality of life, improved cognition with ketogenic diet. And that, again, usually has not been seen with medication trials and other interventions.
APOE4 puts people at much higher risk. And if you have two copies of the APOE4 allele, you're at much higher risk, I think something like nine to 15 times more likely to develop Alzheimer's disease than people who don't have an APOE4 allele. The APOE4 allele a hundred percent. We have very good evidence that APOE4 is involved with brain metabolism and mitochondrial function, and people who have the APOE4 allele in their twenties already have something called glucose hypometabolism, meaning their brain isn't getting enough energy from glucose. And so there are people that I know who actually are APOE four positive, one person who's got two copies of APOE4 allele who are using ketogenic diets in the hopes that that will reduce their risk. We don't have trial data, we don't have long-term data. And the challenge is that we would need long-term data, and we would need a control group.
I've got a friend who has two copies of APOE4. We would never be able to determine whether the ketogenic diet had an effect on him or not. Let's say he develops Alzheimer's disease when he's 85. Did the ketogenic diet work for him or not? We won't know because maybe he would've developed Alzheimer's disease when he was 65, and the ketogenic diet got him 20 years of improved health and delayed onset by 20 years. That would be phenomenal progress and a phenomenal treatment. But because we don't have a control group, we wouldn't know what would've happened to him had he not done the ketogenic diet. So unfortunately, I think we're a little ways away from really getting definitive data on that.
Dr. Dan Stickler: Yeah, that's one I struggle with a lot because I don't feel comfortable putting an APOE4 even if they're carrying one allele of it on a high fat diet. It's very uncomfortable for me in that regard in the long term. Well, thank you for all of this information. I mean, this has been just tons of mic drops here, I think. I really enjoyed it, and we could go on for hours, but they have me on a time limit, and I don't want to take up too much more of your time. So thank you for everything, and hopefully we can maybe connect again in the future.
Dr. Chris Palmer: Absolutely. Thanks Dan for having me on.
Dr. Dan Stickler: Thank you.