Keto and Carnivore: Schizophrenia, Depression, Cancer | Dr. Chris Palmer | EP 422

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Hello everyone, I'm speaking today with Dr. Chris Palmer. He's associated with the Harvard Medical School and with McLean Hospital, which is perhaps the world's preeminent psychiatric hospital. We talked today about material associated, for example with his 2022 book called "Brain Energy." Dr. Palmer has been pursuing the hypothesis that many mental disorders, especially the really severe mental disorders, schizophrenia, bipolar disorder, major depression, intractable depression with no apparent environmental cause, let's say, or psychological cause, might be associated with metabolic disorder, mediated primarily by mitochondrial dysfunction.

The mitochondria are basically the energy factories in every cell, and that’s not all they do. Mitochondrial disorder, therefore, is a very serious problem. He's been experimenting with ketogenic diet, in some sense to the diet that my daughter has been promoting, the lion diet, making the case that use of such diets can not only reduce the effect of potential toxins on mitochondrial function but also increase mitochondrial metabolism and help the body heal by putting it into a state known as autophagy or mitophagy, which are states where the body is actually taking itself apart as a consequence of food deprivation, and then rebuilding itself.

Anyways, he makes the case — we'll discuss the probability that this kind of hypothesizing has gone beyond the merely anecdotal to the point where there is a tremendous amount of research supporting the proposition that dietary factors play a major role in the genesis of such severe mental disorders, and not only mental disorders, also physical disorders like obesity, heart disease, cancer, diabetes, you know, the common enemies of mankind. So, we're going to discuss that in detail.

Thank you for joining us, Dr. Palmer. Let's start out at the level of conceptualization in your 2022 book. Correct me if I get any of this wrong, because I don't want to put words in your mouth. You're concentrating at least on the relationship between, I would say, brain dysfunction, biological dysfunction, metabolic dysfunction, and what we generally think of as mental disorders.

The typical, more abstract psychological conceptualization would be that a mental disorder is something associated with psychopathology and undue suffering, let's say, with dysfunction in the social environment and so forth. It might be a consequence of faulty beliefs and perceptions, and so they can get bent to the point where they're indistinguishable from delusions, and then also skill deficits, which is often what behaviorists remediate.

It’s obvious that a skill deficit in social ability, for example, isn't equivalent to a metabolic disorder, but let me start by asking you how you lay out your conceptualization of metabolic disorder and what implications you think that has for the diagnosis and further understanding and treatment of so-called mental disorders.

You know, it's a complicated situation as you even just began to hint at. You know, maybe one easy way to outline my conceptualization is that there are mental states and there are mental disorders. All humans will suffer; all humans will have anxiety at some point or another in their life. All humans will get depressed, or most humans will get depressed if they experience tragic loss, humiliation, and shame, and those are not brain disorders as far as I'm concerned. That is the normal state of being a human being.

As you alluded to, depending on your upbringing and your experiences, you might learn maladaptive themes or maladaptive lessons in life — people aren't trustworthy, you can't trust anybody — and you go through life that way, and that can have very serious consequences for people. But I don't think those people have brain disorders. The reason they believe what they believe, the way that that happened, is all obvious once you understand the person's full history.

There are myriad ways in which humans can suffer and develop maladaptive patterns that do not include brain disorders, and psychotherapy can be helpful; all of the life skills that you talk about apply to those people. Yet, there are other people who have brain disorders; their brains are malfunctioning. They have anxiety or panic for no reason. They have crippling OCD for no clear reason. They have crippling unrelenting depression for no clear reason. They have hallucinations, illusions, manic episodes, and other types of symptoms, and it is largely believed in the psychiatric field that these people do in fact have brain disorders and that their brains are malfunctioning.

At the end of the day, what I am arguing is that there is, in fact, a central theme to these malfunctioning brain symptoms, and they revolve around metabolism. If we take this global picture and understand that these brain conditions are actually metabolic in nature, number one, it can help us better understand how all of the risk factors can come together to result in mental disorders or mental illness. But much more importantly, it gives us clear, actionable treatments that we typically do not use today. They span a wide variety of different treatment strategies, but they include things like changes in diet, changes in exercise, looking for hormone or vitamin deficiencies, thinking in a more sophisticated way about substance use, and thinking in a much more sophisticated way about the medications that we prescribe for psychiatric conditions because some of them can improve brain metabolism.

But we know that some of them are actually harmful to metabolism. Let me outline a diagnostic approach to you with regards to the differential diagnosis of depression, and I've thought about this a lot, so tell me what you think, and then we'll turn to a discussion of the list of contributing factors to physiological brain dysfunction or illness, and we can tie those together.

Okay, so one of the things I noticed as a clinician, and I think that this is key to solving the mystery of perhaps the differential response to serotonin reuptake inhibitors and other antidepressants. Now, I don't think it's the only key, but I think it's an important one. I don't think it's one that's been attended to enough. So, I noticed in my practice that there were two broad classes of people with depression. Okay?

So we can define depression first for everybody watching and listening. So depression looks like a condition analogous to an excess of pain. It's associated with grief, shame, and guilt. It's characterized by a decrease in positive emotion and motivation — so less enthusiasm, less curiosity, less hope, often hopelessness per se — and a proliferation of negative emotion. And those are separate biochemical systems to some degree. So if you're really depressed, you have no positive emotion, you have way too much negative emotion, and then that manifests itself. Well, it can manifest itself as a virtual inability to move, even, no motivation, and often an overwhelming sense of doom and a proclivity even towards suicide. So that's the depressive realm; it's a psychogenic pain condition, and it differs from anxiety, even in its — although they overlap.

Now, I had clients who were in that condition, but then imagine that those broke into two classes. I have the odd client who, by all appearances, by all standards of multidimensional assessment, had fine lives. So these would be people who were reasonably healthy apart from the depression, let's say, who had a functioning marriage, who had friends that they liked, and a marriage that they liked, even though the depression might have been twisting their perception of that.

So, for example, they may have thought that they were now so useless and contemptible that no one — like their wife — could possibly love them and that they were a burden to their family. But they still had tight family relationships. They often had careers that were well-developed and going fine. They were about as educated as you could expect. They didn't necessarily have any substance use disorders; they did productive things outside of work. But they were profoundly depressed, okay?

So that's one category of person. Now, the other category of person wasn't like that at all. They had no relationships, they had no stable marriage, they had no friends, they had no job, their educational history was fragmented at best, they had no plan for the future. They didn't have a life. Now, both of them were miserable and maybe even equitably in an equivalent manner, but the first group of people with a functional life was very much unlike the second group.

Now, what I noticed, and I've never found any literature directly pertaining to this — maybe you know of some — I found in my practice that if I recommended to those clients, the ones who had a functional life, that they try an antidepressant, it was often likely to have relatively miraculous effects. Whereas the people in the second category, the antidepressant could maybe help ameliorate the worst of their suicidal ideation and possibly tilt them a little bit more in the direction of positive motivation, but generally speaking, not a very effective treatment.

Now logically, because if all those things were absent, the mere offering of a biochemical treatment wasn't going to, you know, provide someone with no partner with a highly functional marriage. So, I think in that differentiation we can also see a distinction between the biological, and that would be what was hypothetically plaguing the people with functional lives, and the conceptual because it was the absence of the ability to go about forming all those relationships, say, and pursue all those pathways in the latter case.

So the first thing I'd like to ask you is your general thoughts about that diagnostic approach to distinguishing between the biological and the so-called psychological, and then how you go about doing that because you already pointed out that you accept the distinction between biological mental illness, let's say, and well conceptual disarray, something like that, or lack of skill.

Yeah, so I think you just did a great job of articulating that framework that I just outlined, that there are some people who have brain disorders; their brains are doing things that don't make sense — they don't make common sense. The first person that you described, or that first category of people you described, it doesn't make sense that that person's depressed. They've got a good life; everything's going well for them, and they will often even say that. They will say, "I don’t know what's wrong with me, doctor. I don’t know what's wrong with me. My wife loves me, my kids love me, I have a good job, we finally saved up enough money to get that vacation home that we wanted. I just got a promotion at work, by all intents and purposes I should be happy, and I am miserable, and I feel like a burden, and I don’t know what's wrong with me, please help me."

I would argue that person has very likely has a brain disorder. The pathways that are hardwired in the brain to trigger the depression response are malfunctioning; they are misfiring; they are causing the sensations and all of the experiences and perceptions of depression when they shouldn't be.

And here's an easy analogy: all humans will experience pain; pain is a normal human experience. If we injure ourselves, we will feel pain; if we get surgery, we may have prolonged and extensive pain. Those are not disorders; they cause suffering, and people often want help for that, and people often want treatment. They might even take pills for it or they might need physical therapy or something else. So, it's not that we don’t treat pain; it's not, but they don't have a pain disorder.

And then there are other people who have pain disorders; their pain system is malfunctioning and causing the sensation of pain when there's no clear good reason for pain. So, that gives us a framework of normal and extreme. If you get surgery, you may have extreme pain, but those aren't disorders. Then somebody who's got a pain disorder where they have chronic unrelenting pain for no good reason — their pain system is malfunctioning.

And so that first category person, I would say their brain — the networks that cause all of the different experiences of depression — those networks are malfunctioning. They are either overactive or underactive depending on what symptoms we're looking at. But they've got a malfunctioning brain that is causing the experience of depression.

The second category that you mentioned, the person whose life is just a tragic mess, they have never had anything good going for them; they don't know how to create a good life, they don't know how to take care of themselves, how to have good positive relationships. Maybe they have no purpose in life. Those people will in fact experience depression, and if they don’t experience depression, that in and of itself is a disorder.

Anybody in that circumstance should in fact be depressed because the human brain is hardwired to make that person depressed, because the human brain is trying to get that person to get a life, to integrate themselves into society so that other humans actually accept them. That integration is vital for safety. We, as humans, are supposed to be connected with others, and that creates safety. If we're not participating in that culture, in that society, that means we are an outcast; we are being shunned.

There’s something wrong, and those people will, and that's a danger. So, one of the things — let me ask you what you think about this. There is a relationship between the degree to which a given brain is likely to produce serotonin and the relative social status of that person. Higher social status correlates with lower levels of depression, anxiety, and poor mental health outcomes.

So as someone who’s low status, you are more likely to have an exaggerated response to stress, and that can kill you over time, and that's very well documented — a very high relationship between relative social status and risk for mortality.

But the reason for that — and you're pointing to this — because someone might think, "Well, you know, your claim that you need to be integrated within a social community is just an arbitrary claim. There's nothing based in reality about that; it's just a supposition of normality, and there's no reason to assume that it's related to mental health."

But the reason that's erroneous is because you're much more likely to have opportunity and to have security of the genuine sort. That kind of security can save your life if you have a very well-developed and functional social network and you're very well regarded and respected and integrated within that.

As you intimated, we do have systems that perceive that, and that causes pain in the absence of that, and that is definitely a contributing factor to depression — not some arbitrary moral presupposition; it's hardwired into the fact that we are incredibly interdependent and social creatures.

So much so that, this is something for everyone to think about too, we’re so wired to need that social harmony and interaction that we can even punish the most vicious and psychopathic antisocial criminals by putting them in solitary isolation. So, even those guys can’t do it alone.

Okay, so depression can be a valid marker of the inability to be integrated, right? It can become counterproductive even under those circumstances. But the condition in itself, just like the condition of pain, isn’t an indication of pathology.

So, okay, so let's talk about differential diagnosis. We’ve already agreed as far as I can see that there’s a difference between a physiological disorder and a more abstract or mental disorder.

Now, the other thing I tried to do in my practice was to rule out the physiological before proceeding with the psychological. You pointed to a bunch of potential contributors to the physiological. So let me list those and then maybe you can tell me if I missed any, if you dispute any, and how you go about that diagnosis.

So here’s some things that can make you mentally ill apart from the contents of your thought or perceptions. We know that depression is often associated with markers of excess immunological activity. If you’re in a cytokine storm, you can get depressed. There are all sorts of dietary reasons that we could delve into. There are all sorts of illnesses that can produce depression as a side effect. There’s an issue of adverse response to medication. It might be that you’re in bad physical shape and need to exercise more.

Some people are more prone to depression in the absence of exercise. There’s a huge potential complication of toxin exposure, environmental and otherwise. Then there's an associated problem — like one of the quick pathways to depression, especially if you're biologically tilted in this direction, is to drink to relative excess three times a week, because then you’re always in alcohol withdrawal.

So, another thing that a good diagnostician should do is think, "Well, this person presents with depression, but maybe they’re ill," and here’s 10 things we should look at to rule that out.

So tell me what you think about that and how you go about doing that when you’re actually seeing your patients.

I think all of the things that you mentioned are absolutely spot on. I think that they can all play a role in the physiological brain disorder type of depression — that all of those things can result in the brain malfunctioning and producing the experience of depression when in fact the person doesn’t have psychological or social reasons to necessarily be clinically depressed.

You know, you mentioned medical diagnoses; I think that’s a very broad field because numerous medical conditions are associated with increased risk for depression. All the way from all of the neurological disorders — epilepsy, Alzheimer's disease, Huntington's disease, Parkinson's disease — to hormone imbalances — hypothyroidism or low thyroid hormone. Women’s hormones; a lot of women experience mood changes, mental health symptoms just around the time of their menstrual periods.

They may have significant changes around, you know, around the time of pregnancy and immediately after pregnancy, and they can have significant changes around the time of menopause. Men can experience similar symptoms if they have low testosterone.

So there are a wide range of medical conditions that can all result in the exact same symptoms of major depression, and that in my mind, is very curious. We in the mental health field just shrug that off. But what it suggests is that all of those things are somehow connecting through some common pathophysiology.

And in my mind, that is actually a really important clue to solving the puzzle of mental illness, like what causes mental disorders, what causes this tremendous suffering in millions and millions of people around the world. How can we develop better treatments by recognizing that all of those things must share something in common to produce the exact same constellation of symptoms?

That's actually really useful information, and in my mind, the common thread is that they all impact metabolism. More specifically, these tiny things in our cells called mitochondria.

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Okay, well, then, let’s say that I would be very interested in hearing much more detail about that. So, you know, because I’ve delved into potential physiological causes for exacerbated pain sensitivity, let's say, and the entire depressive spectrum of symptoms, but not precisely on the metabolic front.

So when — why did you, given the plethora of contributors that we've already discussed to the problem of depression, and then the broader problem of mental disorder — why did you feel that concentrating on metabolic dysfunction per se was the most useful tack to take?

And maybe, so let’s do two things; why don’t you tell us in some real detail what you mean by metabolic disorder all the way down to the mitochondrial level, with perhaps an explanation of the function of mitochondria, and then tell us why you think that's particularly worthy of focus given all the other contributors? Maybe as a common final pathway, even given all the other contributors to depression.

So, right now, if you ask the leading psychiatrists and neuroscientists in the world what exactly causes mental illness — and we can stay focused broadly on all of the mental disorders or we can just hone in on major depression — that first category of depression that we talked about, that somebody they don’t have a reason to be depressed psychologically or socially and yet they’re showing all these signs and symptoms — like what is going on?

If you ask the leading people, they will say, "Yeah, it's just too complicated; nobody can figure it out." But we do know our risk factors, and we talk about this biopsychosocial model of risk factors and we say that there are biological things — neurotransmitters, hormones, genetics — that play a role, but there are psychological and social things.

People can develop mental disorders, like the brain disorder type of thing, from prolonged trauma or social adversity in childhood, or loneliness and disconnection, and those things also contribute to mental illness. But exactly how do they come together?

Right now, the leading people will say no one knows; it's too complicated. The way that I came to metabolism is because I had some really important kind of pieces of information that were quite shocking. I was actually using dietary strategies — pure serendipity. I did not set out to do anything special, but I was changing people's diets to help them lose weight and noticing dramatic improvement in psychotic symptoms, mood symptoms, and other symptoms.

So, okay, so you came at this — you started to understand this because you started to examine diet, and you were examining diet. You were examining diet why exactly? What was just to help people lose weight?

This will take me on a tangent from the question that I'm going to come back to, but this tangent is that I had this patient with schizoaffective disorder. He had been my patient for eight years. Schizoaffective disorder is a cross between schizophrenia and bipolar disorder. This man was tormented and disabled by his illness.

He had chronic hallucinations, delusions, he was paranoid; he was convinced that everybody in the world was out to get him. People were laughing at him, spying on him, trying to hurt him. He had tried 17 different medications; none of them helped his symptoms. He had gained a massive amount of weight and asked for my help to lose weight, and I put him on a ketogenic diet to try to help him lose weight.

Within two weeks, not only was he starting to lose weight, but I began to notice this powerful antidepressant effect in him. The shocking thing that led me ultimately on this path was that about two months in — so it doesn't happen overnight — but about two months in, he starts spontaneously reporting that his hallucinations and delusions are starting to go away.

That man went on to lose over 160 lbs, has kept it off to this day, six years later. He was able to do things he hadn't been able to do since the time of his diagnosis. He was able to go out in public and not be paranoid; he was able to complete a certificate program; he was able to perform improv in front of a live audience; he teaches karate now.

Now, he was able to do things that were all but impossible for him and somebody with his diagnosis. Initially, I was just in disbelief; I couldn't believe what I was seeing. I'm thinking, "This can't be happening; schizoaffective disorder doesn't get better, and it certainly doesn't get better from a change in diet. What on Earth is happening?"

So I initially set out on a journey to understand what on Earth is the ketogenic diet doing, and I was quickly led to its use in neurology. So although a lot of people know the ketogenic diet as a fad diet or a weight loss diet, it's actually a 100-year-old evidence-based treatment for epilepsy, and it can stop seizures even when medications fail to stop seizures.

The reason that's so important to me as a psychiatrist is because we use epilepsy treatments in psychiatry every day. Ten million people we use pills that were originally designed to stop seizures, and we use them for a wide range of mental disorders, including depression, anxiety, alcoholism, dementia, schizophrenia, bipolar disorder, and others.

Initially, that was a really important connection because I thought, "Well, maybe that's why this diet is changing his brain symptoms. Is whatever it's doing to stop seizures, maybe those same processes are also reducing his psychotic symptoms, like reducing excess neural activity, for example?"

Because you could imagine that that delusional state is a — I'm not saying this is the case, but you could imagine that it is the case that it is a consequence, at least in part, of excess neural activities. Now, if you have too much neural activity, you're going to get the electrical storm that characterizes epilepsy, but you could imagine that a man could be in a psychophysiological condition where the spread of ideas around the core idea is too rapid and too wide.

And a delusion certainly looks like that to some degree, especially a paranoid delusion. You even see that to some degree in depression because in depression, one sad idea will trigger an avalanche of sad ideas.

So, well just a thought with regard to the potential overlap with epilepsy. Okay, so you started looking at the dramatic, as you pointed out, dramatic effects of ketogenic diets on epilepsy treatment and started to think if that — given that that dramatic effect on brain states exists, which is clearly documented, right? And no one disputes it — there’s no reason to assume that there couldn't be more subtle but still important effects of dietary transformation, and then you became partly convinced of that as well because of the — I mean the story you tell of that one client is a ridiculously dramatic story.

Because schizoaffective personality disorders are notoriously difficult to treat. Schizoaffective disorder is a complete bloody catastrophe because it has all of the aspects of personality disorder that’ll produce social alienation plus all of the intense suffering that's characterized by the whole hallucinatory nightmare of delusion. So it’s a very, very serious, personality disorder, neuropsychiatric condition. And then you saw this dramatic transformation in this one individual, not only on the weight side, which is dramatic enough and unlikely enough, given that most people never lose their weight, right? They’ll lose it for a time, but they gain it back, and also the cessation of the symptoms.

And also, this makes it even more complex, because it took two months. This is not an easy thing to discover — right? I mean, the person has to be pretty damn committed to the dietary transformation and also unlikely to cheat in the interim.

So, okay, so you encountered those. Let’s return to the metabolic story.

So initially — well, and I want to back up just a little bit and just forgive me, but I want to just correct something that you said. Because I’m talking about schizoaffective disorder, which is really the full-fledged cross between schizophrenia and bipolar disorder.

Oh so, oh I see, it was even more serious. It was even more serious — he basically had full-fledged schizophrenia. Full-fledged psychosis. I see.

Okay, and so as I went on, you know, initially, I’m starting to use it with other patients, and I’m seeing equally transformative and sometimes even more transformative results, so I know I’m on to something. But I also recognize nobody’s going to believe this; nobody in the medical field is going to believe that a diet could change something as devastating as schizophrenia.

So I need to come up with at least a potential mechanism of action. I need to understand enough science to be able to make the case, to be able to report this in the medical literature.

And the great news is that I had two bodies of literature to call on. There’s an entire body of literature in the neurology field on how on Earth does the ketogenic diet stop seizures, and there are all of these known mechanisms of action, including changes in neurotransmitters, changes in the gut microbiome, decreasing inflammation, all of these things.

But one thing stuck out at me: it improves mitochondrial function, and it improves brain metabolism. The other body of literature that I had to look at, though, was the schizophrenia literature and the bipolar disorder literature to see, "Well, what do we know about the neurology and the neuroscience of those disorders? Is there any overlap?"

And the widely held view is that schizophrenia is just too much dopamine. That's what schizophrenia is: too much dopamine. But that didn’t sit with this observation that the ketogenic diet is dramatically reducing symptoms. The dopamine thing didn’t fit in.

And so I had to look elsewhere, and I was led to this entire body of literature, two decades long now, documenting that mitochondrial problems may in fact be the central root cause of schizophrenia and bipolar disorder.

Okay, let me ask you a question there. So, well the dopamine hypothesis has been around for a very long time, and it is the case — and it’s been a while since I reviewed this, so if I have — if there’s anything that I’m saying that’s no longer like that’s out of date, let me know. Part of the evidence for that was that at least with some forms of schizophrenia you could exacerbate the symptoms with amphetamines and that you could also produce amphetamine-related psychosis. That’s part of the body of evidence.

The other part of the body of evidence is that the antispychotics, the major antispychotics do seem to work, like anti-cocaine or anti-amphetamine, and they do quell the more florid symptoms of schizophrenia especially in its acute manifestations rather than the sort of burnout schizophrenia that's characteristic, maybe, of the much longer-term illness.

So, given the prevalence of that hypothesis and the support for its validity, did you see any overlap between the metabolic hypothesis and the dopamine hypothesis?

Like is the dopaminergic malfunction, in your estimation, a secondary consequence of a deeper mitochondrial malfunction, or do you think that the dopamine hypothesis is more something akin to observation of a symptom pattern rather than the core cause? Because no one knows why the dopamine system dysregulation — anyways.

I think that’s the key. First and foremost, I want to say that everything that you just said is true, and that is in fact the basis for the dopamine hypothesis. However, it doesn’t fully account for all of the information that we currently have.

We know that serotonergic antidepressants — things like Prozac and Zoloft — can also exacerbate psychosis in people with bipolar disorder or schizophrenia or other disorders. We know that sleep deprivation can exacerbate psychosis in a wide range of people; certainly people with schizophrenia, but even in normal healthy people if we sleep deprive them long enough, they will begin to hallucinate or have delusions.

So that starts to suggest, "Wait. Serotonin now plays a role in sleep deprivation." How does that all fit together? Does that all converge at dopamine? It does not. It does not converge at dopamine. However, if we think about, well, what could cause dopaminergic neurons to be overactive and spew out more dopamine than they're supposed to be spewing out, then we actually come back to the mitochondrial or metabolic theory that I'm proposing.

The metabolic theory can actually explain to us exactly why neurons might be overactive, or the neuroscience term is hyperexcitable. We've got decades of science, neuroimaging studies, cell biology studies and others where we know for sure that people with these brain conditions have hyperexcitable neurons.

There are parts of their brain that just start firing when they should not fire, kind of like a pain cell starts firing when it shouldn't fire. And so, to understand well, what would make a cell start to fire for no reason, what would make it hyperexcitable or overactive, we actually can turn to the metabolic or mitochondrial theory because that actually connects all of the dots.

That can help us understand why would Zoloft or Prozac cause psychosis. That can help us understand why would sleep deprivation cause psychosis, and it certainly confirms what you outlined: why would amphetamines or cocaine cause psychosis?

And I think that, you know, the way that I came to this is I started looking at the entire field, initially just trying to connect the dots for how on Earth could a ketogenic diet stop psychotic symptoms in somebody who presumably had a lifelong genetic disorder.

That is what most people think of as schizophrenia: it is a lifelong genetic disorder. It’s permanent. It’s fixed. There essentially is no hope for this person. So, I’m trying to understand how on Earth could a diet do that.

As soon as I put all of that together, though, and started focusing in on mitochondria and metabolism, I started branching out to other diagnoses. The reason I started branching out to other diagnoses is because we have a problem in the mental health field.

Although we have all of these nice diagnostic labels—like schizophrenia or bipolar or alcoholism or anorexia or OCD—and we pretend that they are all separate and distinct disorders; the reality is that a lot of the people that we treat in mental health clinics have more than one of those diagnostic labels.

It is rare for somebody to have schizophrenia and only schizophrenia. Almost always they have schizophrenia and some substance use problems, and some OCD, and oh, and depression. Well, wouldn’t you be depressed too if you had schizophrenia? And oh, and anxiety. Well, wouldn’t you be anxious if you had schizophrenia?

We rationalize it away, but it cuts across all of our diagnostic categories. There’s this overlap.

So, I started looking into, is there any meta -- is there any evidence that metabolism or mitochondria could play a role in these other mental disorders?

At the end of the day, what became overwhelmingly clear is that we, for decades, have been accumulating this evidence, and nobody to date has really put it all together, but it is in fact a way to put all of the evidence that we have accumulated for decades, it’s a way to put it together and have it fit and have it make sense.

But once you understand that science, it leads to solutions that may actually help people heal and recover from disorders that we are currently telling people are lifelong, incurable disorders.

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Okay, okay, so let me — I want to step through that in a sequence. The first thing, okay, let me recapitulate:

So you pointed to first the fact that there's a tremendous amount of comorbidity or diagnostic overlap between the hypothetically separate categories that we describe as the various mental illnesses. Now we know that's true, not least in the fact that for the mental illness to come to the attention of a psychiatrist or a psychologist or an MD, for that matter, it’s usually a consequence of the exacerbation of negative emotion and the decrease of positive emotion.

So there is a place where there’s immense overlap, right? Because it’s just not a problem with the possible exception of mania. It’s just not a problem that comes to people's attention unless one of the major areas of overlap is a preponderance of negative emotion, the suffering we described.

But then you describe that even more densely, pointing out that these hypothetically separate diagnostic categories, when you aggregate them, they have a tremendous area of even symptomatic overlap.

I know for example, can’t remember the study now, but showed that if you do have a person with a so-called personality disorder, imagine you could make a list of all personality disorder symptoms, and the one thing you would get to know from that list checklist was how many symptoms the person in front of you had.

That's a much more useful prognostic indicator than diagnostic category, right?

So there’s tremendous overlap of symptomatology. Now you think that points to an underlying commonality of cause, right? And that and that and that you’re hot on the trail of this metabolic insufficiency.

So let’s start if you would walk us through what the mitochondria do. Tell us why deficits in mitochondrial function — like what they would produce — because, well, one of the things that happens just as you age is your mitochondria start to become less and less effective.

So, and not everybody who ages shows signs of mental disorder, although depression and pain, etc., associated with aging are far from uncommon. So, take us down to the mitochondria; tell us what they do, tell us how that would manifest itself in neuropsychiatric disorder and then maybe we can move to that, because the next question is, "Okay, fair enough. Why does the keto diet specifically work and is that the best of all possible intercessional diets?"

Then we can think about, "Well, where should that also fit conceptually in the armament of diagnostic and treatment practices?"

Okay, so let’s start with what do mitochondria do?

So, most people who have — who are even familiar with the term mitochondria know them as the powerhouse of the cell, and what that means is that they take food and oxygen, and they turn it into ATP.

So mitochondria are the things that are actually using oxygen. So we breathe in oxygen and we breathe out carbon dioxide. Mitochondria are using that oxygen, and they are producing carbon dioxide that we breathe out. Mitochondria are taking the food — so we have our digestive tract and other kind of enzymes throughout our bodies that are breaking food down — but ultimately, most of the food, at least 90% of the food that we consume, ends up inside mitochondria.

So mitochondria are the processors of food, and when they get food, they convert it into one of three things. I could probably come up with more categories, but I'll name one of three things.

The three things are: they convert it into ATP, which is the power unit of the cell, and that's why they're called the powerhouse of the cell; they're creating energy or ATP. The second thing that happens to food that we consume is it may not go all the way to ATP; we might just break it down into smaller molecules.

Then we use those smaller molecules to produce enzymes or proteins or neurotransmitters or hormones or cell membranes. So our bodies are in fact composed of food that we ate. The food that we eat gets broken down and it turns into our cell and our neurotransmitters and everything else.

The third thing that can happen is that mitochondria actually can sometimes divert that energy and instead of making ATP, or making molecules to build cells, they make heat. In fact, mitochondria are the reason we are warm-blooded animals. Without them, we would not be warm; they can subtly — they are the things that are making heat. If you get a fever, they are creating that fever. If you're too cold, it's because they're not firing enough; there's something wrong with their system.

That’s what most people know. Research over the last 20 years has completely shattered that simplistic notion of what mitochondria are. This is the reason; some people ask, "Like Chris Palmer, how on Earth are you coming up with this, and if it's really true, why hasn’t somebody else come up with it?"

Part of it: number one, a lot of other people have kind of sort of come up with what I’m arguing, and they are hot on this trail and continue to be hot on this trail. So I'm not alone. But one of the reasons most people have not put it together is because this is a cutting-edge area of research over the last 20 years — not really in the mental health field; it's more in the obesity field, the cardiovascular field, the aging field, the Alzheimer’s disease field.

All of these are looking at what do mitochondria do, so that they can better understand their diseases. Let me just give you a brief snapshot of what mitochondria do, and you'll begin to understand how it starts to connect to the mental health field.

Mitochondria make, and they help create, regulate, and release neurotransmitters, including serotonin, dopamine, norepinephrine, GABA. In fact, those neurotransmitters then impact mitochondrial function, so it's a two-way street. The neurotransmitters affect mitochondria; mitochondria are making and releasing, or helping to release those neurotransmitters.

Mitochondria help control the expression of genes from the cell nucleus. That's the whole area called epigenetics. Mitochondria are central to epigenetic expression in cells. Mitochondria help turn inflammation both on and off.

Mitochondria control the first step in the synthesis of some key hormones, including cortisol, estrogen, testosterone. So we've long known that HPA axis kind of disregulation — too much cortisol or too little cortisol — we've known that that’s disregulated in people with mental illness. What would cause that disregulation?

Actually, mitochondrial disregulation is in fact the leading theory for what could cause that disregulation, because they are controlling the first step in the synthesis. They are affected by our diet.

Our exercise, drugs, and alcohol impact their function. But here’s the kicker: trauma, childhood adversity, directly impact mitochondrial function and health. It is a way for us to begin to integrate the bioc psychosocial risk factors that we know can play a role in what we call mental disorders.

In mitochondria, their function or malfunction can begin to help us piece the puzzle together.

Okay, so let me summarize that, and tell me if I’ve got my understanding right. So you pointed out that classically speaking, mitochondria are regarded as the furnace, the energy source of the cell and therefore the body, have been studied in relationship to their ability to produce from the food we eat ATP, which is the fundamental molecule by which we fuel ourselves, let’s say.

And then, a plethora of chemicals and molecules and also produce heat. Now it sounds to me like what you've claimed is that over the last 20 years, that chemical and molecular production function of mitochondria has been differentiated and delineated far more comprehensively.

So now we understand that mitochondria are crucial for the production of various hormones and neurotransmitters: they’re part of the factory that does that. They’re also, as you said, associated with the initiation and sensation of inflammatory responses and also the regulation of gene operation.

And that’s where we got into a discussion of epigenetics. So for everybody watching and listening, correct me if I've got this wrong: Dr. Palmer is saying like genes are part of the biological code that lays out our physical and psychophysiological function from the ground upward. Genes can be turned on and off, and they're turned on and off according to environmental demand.

There are other reasons they can be turned off and on, but that's one of them. And so you’re pointing out that mitochondria play a role in the switching on and off of genes, like they do in the switching on and off of inflammation and the production of hormones and neurotransmitters.

So that's another reason why delving into the cell down to the level of the mitochondria is a good place to be looking for the common pathway that we’re searching for with regards to the generation or the initiation of mental illness.

Okay, so I’ve got that right, yes? That's a reasonable — okay, so then let's go to — okay good, good. Well, then let’s go to diet.

Now I want to lay out another question for you. So, as you may know or may not know, and the same would apply to people who are watching and listening, my family has been experimenting a lot with a radical keto diet and an all-beef diet with salt, and there are a variety of reasons why it's all beef, which I won't go into. But here's the fundamental issue from the scientific perspective, and you can tell me what you think about this more broadly and why you're investigating a keto diet, which is less strict than a carnivorous diet.

So one of the things we thought and experimented with when we were trying to sort out my daughter's autoimmune illness was, well, see, we had her tested at one point for allergies to foods, for example, and the basic test came back in skin test and showed she was allergic to everything.

Now, we thought, "Well, what's the probability that she's going to be allergic to everything?" It seems unbelievable. But I did know at that point — and this is to your point with regards to diet — one of the most reliable treatments for arthritis, and this works with virtually everyone, is if you fast, your arthritis goes away.

Now, the problem is it comes back when you eat anything. It’s like, "Well, wait a second, anything is a lot of things." So then you might say, "Well, if you were going to investigate a potential dietary link with pathology, you’d want to find the simplest possible — we had her on some like so-called elimination diets, but they made no conceptual sense and there were still things within it that looked very contradictory."

So I understand your impetus, your insistence on the utility of experimentation and your proclivity to presume that there’s no one-size-fits-all solution, but we have said that having said all that, a keto diet and a carnivorous diet does produce autophagy and mitophagy, and that's a very necessary thing.

And it also is a very simple approach, even though you know it’s behaviorally complex, and that’s a problem because it’s actually hard to only eat meat. So what do you think?

Are you willing to speculate on what might constitute a reasonable generic approach to dietary experimentation? Because it is a complex thing to undertake.

So, I completely agree with your approach and your kind of — I agree that a carnivorous diet may in fact be the gold standard elimination diet to see if a change in dietary pattern can produce the health benefits that a person is seeking.

The reason I’m hesitant to recommend it for everybody is because I already know the nutrition experts will vilify me along with you and Michaela and others, and so I want to throw — are those the same experts that recommended the food pyramid?

Don't get me started on that because that food pyramid really messed up my own personal health.

But so, for the people who say, "Well, no way I’m only going to eat meat," then I want to at least meet them where they’re at and say, "Fine, you don’t have to only eat meat; there are lots of options." You could try the FODMAP diet, you could try other diets, you could try a whole food plant-based.

I don’t want to give up on them, and I don’t want to let them know that it’s like carnivore or nothing. So I want to be able to understand, however, if somebody is really, really sick and needs a drastic intervention, doing a water-only fast — maybe with some electrolyte supplementation and other things — doing a medically supervised, even, because if this person is really sick, they’re already down and out, and so maybe we need to monitor them.

Doing a water-only fast is really the ultimate elimination diet because we’re eliminating all food; we’re really letting the digestive tract rest and repair. If the digestive tract is inflamed, we’re allowing maybe that inflammation to subside. We know that there is a gut-brain connection and that that plays a role in a wide range of mental disorders — all the way from autism to depression to anxiety to schizophrenia to binge eating disorder to bulimia nervosa.

There’s a wide range of mental disorders; we have a growing body of evidence that the gut — actually problems in the gut get transmitted through the vagus nerve and through other endocrine pathways through serotonin, actually, and other pathways up to the brain, and that directly impacts brain function and/or brain metabolism, brain metabolic function, which then impacts neurotransmitters and everything else.

So a water-only fast would be maybe the most drastic intervention, but again, you can’t — you can’t fast for too long because you're going to starve to death, and I wouldn’t want to do that in an underweight person.

The second best version is exactly what you've described: the lion's diet, which is meat, just meat; beef alone is enough nutrition to sustain a human.

There will be people already — I can hear people already saying, "Fiber! Fiber is really good, Dr. Palmer. How dare you get rid of fiber?" And so the thing is, is I think you're right, though, that if somebody's really in trouble with serious symptoms, or if somebody just wants to do maybe a one month or three month experiment to see will this improve my symptoms, I would actually encourage people to give it three months.

Right? That's about what we've concluded too; it's about three months. Do a carnivore diet or a ketogenic diet if you don’t want to do that. Because I have some patients who, you know, I’ve talked about the carnivore diet with them and they’re like, "No way! No way!"

I'm like, "Okay, well, let’s do a therapeutic ketogenic diet." The therapeutic ketogenic diet I can solidly stand behind. And the reason I can solidly stand behind that — you know, the carnivore diet is a ketogenic diet — but there are other variations of ketogenic diets, and the reason that I can solidly stand behind the ketogenic diet is because we have an enormous evidence base — all the way from animal models, cell biology models to human clinical trials of ketogenic diets for seizures, for weight loss, for type 2 diabetes, for type 1 diabetes, for kidney disease, for cancer, and other conditions.

And we have good evidence that a ketogenic diet can in fact be safe, can be highly effective for many of those conditions. And so I just stand solidly behind that science or on the shoulders, so to speak, of that science.

But I don’t disagree with you in terms of what you're saying about the carnivore diet and some of the benefit. Well, and also I should say too, like as a behavioral psychologist, I mean, there's no sense suggesting something to someone they won’t do.

So if you can generate a plethora of alternatives, some of which aren't quite so extreme and they might work, more power to you.

So, okay, so let me ask you a specific question. I have a specific reason for this. So, my wife had a very rare form of cancer, a benign tumor in her kidney, and the 11-month mortality rate for benign tumors, which have only been reported about 200 times, is 100%.

And she lived through it. Now, she had surgical interventions, and it's a complex story, but we believe tentatively that the reason that this didn't kill her, apart from the surgeries and various other factors that came into play, was perhaps because she was on the carnivore diet and very strictly adhered to it.

Now, I have a more personal reason as well, more specifically personal at the moment for asking you this question. I know of someone who's in very deep trouble; they're suffering from cancer, and I'm wondering, you know, if you have a loved one who's afflicted in that way and they're starting to run out of options — by the way, on the treatment front — and facing the proliferation of their cancer, I know you can starve cancers.

So, as a practicing physician, at what point in the progression of cancer do you think it's reasonable or unreasonable to say, "Look, you got nothing to lose from a water fast for three days followed by like a month or two months of pure carnivore diet," and then we could reevaluate your circumstances at that time.

And so, what—because I'm thinking about having a chat with this person about exactly this, and so I’m wondering, like, what do you have to say?

I'm not a physician, right? And so I’m wandering out of my territory to some degree on the dietary front, although that became necessary for all sorts of reasons, but I'm also extremely interested in the neuropsychiatric implications. So what do you think on the cancer front?

So, I’m not an oncologist, so I want to — I want to say for the record this is way out of my territory. And I’ve actually been asked this question by some close friends even: "Should I do a ketogenic diet? I have cancer. I’m fighting cancer. I’m going to do the curative radiation or surgery or whatever, but should I also do a ketogenic diet?" And my honest advice is because I am out of my area of expertise, I really encourage people to work with their oncologist.

Fair enough!

And the reality is that we have an increasing number of clinical trials that are ongoing right now where they are adding ketogenic and other dietary interventions to the chemotherapy or radiation to see if in fact it may play a role.

And we know that, you know, in general my sense from the published literature — Dr. Thomas Seyfried is kind of an expert in this area of ketogenic diets for cancer.

What’s his name?

Thomas Seyfried, I think.

Okay.

Seyfried. And he’s written a book on cancer as a metabolic illness. In general, once cancer gets started, at that point, it’s probably too late for a dietary intervention in most cases to cure the cancer.

However, we have strong reason to believe — and this is why these clinical trials are getting started — we have strong reason to believe that a dietary intervention like a ketogenic diet or a carnivore diet or water fasting or intermittent fasting may slow the growth of that tumor.

May! And slowing the growth of a tumor gives us more time to do the definitive intervention to get that cancer out of that person's body.

Well, also, there’s good evidence that fasting reduces chemo and radiation-induced nausea, so that also makes the treatment more tolerable, at least in principle.

Absolutely! And these dietary interventions are decreasing inflammation; they are decreasing insulin, and insulin is a growth factor, and it is a growth factor for tumors as well.

So again, we’re basically doing everything we can to try to slow the growth of this tumor while the oncologists are trying to kill the cancer with surgery, chemo, or radiation.

And it sounds, you know, thank you for sharing your wife's story. It’s a really — well, it’s an anecdote, you know, but anecdotes are good!

Well look man, they’re not data, but they’re good sources for hypothesis generation!

I think they are great sources! They are fantastic sources for hypothesis generation, and again, anybody who says, "Well that’s just an anecdote," I would want you to push back and say, "No actually, there are clinical trials underway, and that is not anecdote anymore."

Right!

She is an example of a scientific theory that is progressing through the oncology field already. So, anybody who tries to say, "Well you know that’s just an anecdote"; well no, it's not just an anecdote. There’s a tremendous body of science; there are clinical trials underway now.

There are animal models supporting that ketogenic and other dietary interventions can slow the progression, can actually shrink tumors.

The reason I'm hesitant to say 'cure' is because Dr. Seyfried -- the reason I brought him up is, you know, he has published a couple of case reports in the medical literature.

There was one woman who had what was billed as an incurable brain tumor, a glioblastoma, and she went on a very, very strict medically supervised ketogenic diet, calorie restricted even, and in fact, her glioblastoma shrunk to the point that it was undetectable!

But after about nine months — so they thought maybe she was cured 'cause it shrunk a lot — she stopped the diet; the tumor came back with a vengeance and she died.

So I just point that out that I think that we still have to encourage people to work with oncologists and try their best to kill all cancer.

So maybe we could close this off. Well, first of all, we can close it off if you have anything else that you need to bring to people's attention.

But one of the other things I’d like to hear from you — you know, you told that story of your patient with schizoaffective disorder and his remarkable recovery with regards to his accompanying obesity as well as his mental illness.

What else have you seen that was part of what motivated you to pursue this so assiduously? Tell us more stories.

Well, so I can tell you lots of stories, but I don’t want anybody to come away from this thinking this is anecdotal anymore. Right? For me as a professional, it started with that anecdote.

It is no longer in the realm of anecdote anymore. We have hundreds, if not thousands, of patients with bipolar disorder, with schizophrenia, with chronic unrelenting depression, with OCD, with anorexia nervosa, with alcoholism for God's sakes of all things.

We have people with all of these different diagnoses who are coming out of the woodwork sharing their stories of recovery and sometimes remission. Some of these people are able to get off all of their psychiatric meds and remain in remission.

We have clinical trials underway. At least I think 15 clinical trials underway now at Harvard Medical School, at Oxford, at John Hopkins, at UCLA, at UCSF, many other institutions literally around the world. We’ve got clinical trials underway, so anybody who wants to say, “Well this is just anecdotal evidence”? No, it’s way beyond anecdotal evidence now at this point.

But the stories that I want to share that I just alluded to — a woman who had bipolar disorder had become psychotic when she got manic. So awful, awful illness.

She is sharing her story publicly about how the antipsychotic medications and mood stabilizers that she took made her clinically obese, made her gain massive amounts of weight. She felt awful; she had low-grade depression. She was plagued with recurrent suicidality after starting some of the medications that she had to start, and she has now put her bipolar disorder into remission for over two years.

She heard about me; she heard me on a podcast; she has read my book; she implemented the treatments that I've outlined, and she is off all her medicines in full remission.

I have literally — I have thousands of people reaching out to me for help. So I should say for the record, unfortunately for your listeners, I’m not taking new patients or consultations; I’m really sorry because I’ve literally got a waitlist of over 2600 people already. But I have treated — I’ve treated patients. You know, one person in particular I can share their story publicly because they are very public already, so I am not breaking any confidence.

They are billionaires, literally billionaires. Their son had bipolar disorder, a really bad case of it. He had tried 29 different medications; he was in and out of hospitals, in and out of residential treatment programs, seeing the best bipolar specialists in the world, and they, as a family, he is an individual — she as a mother — were told in no uncertain terms, "Your son has treatment-resistant bipolar disorder. He is going to be disabled for life. You need to accept that. He is going to be sick for the rest of his life. You are in denial. Your denial is the problem. Stop denying that your son has a serious mental illness and he’s never going to get better; just accept it and move on."

They came to me about three years ago now saying, “We heard about you and this diet and bipolar, and we’re not giving up yet. We’re not ready to give up, even though everybody’s trying to encourage us to give up; will you help us?”

I talked with them; I met with his treating psychiatrist, and we partnered together because I’m in Massachusetts; they’re in California.

So I wasn’t legally allowed to treat him as the treating psychiatrist, so I was a consultant. It is now three years. Within four months of starting a ketogenic diet, his bipolar symptoms were in full and complete remission. He is off of probably 75% of the medicines that he had been taking.

So he’s not completely off medicine at this point, but he is slowly but surely tapering off, but he has not had an episode since; he does not have bipolar symptoms. His illness is in remission.

He has finished college; he works full-time; he has a full life; he’s excited to be alive. And this was a man that was being told by the best experts; they were billionaires; they had access to the best of the best, and the best of the best in the mental health field were encouraging them to give up hope. They were encouraging them to just give up; just write him off, just accept that he’s going to be disabled for life, and they refused to accept that. And he’s living a new life now.

And so, they have created a nonprofit organization called Metabolic Mind. They have funded, I don’t, they don’t share their financials with me, but to the best of my knowledge, at least probably $70 million of research now focused on bipolar disorder and metabolic strategies. They are really helping to move this field forward, and we’ve got an international team of psychiatrists, neuroscientists, mitochondrial biology experts, metabolism experts all working together to move this field forward.

I just got a major gift, a $3 million gift, from a different philanthropist to start a new program at McLean Hospital, the Metabolic and Mental Health Program. And we are going to be launching this.

So for people who listen to this and are skeptical, I get it; you have every reason to be skeptical. This is new and shocking information, and I am trying to encourage people to not give up hope. I am trying to encourage people that even if you’re told that there is no hope — that you just need to accept that you’ve got a chronic horrible debilitating illness and that’s just the way it is — I want you to rise up; I want you to learn more about this work; I want you to learn more about what you can do, and I want to empower people, first and foremost, with hope and then with knowledge and then with practical strategies that they can implement.

Just like you and your daughter and your wife and others have implemented. You take control; you learn things, you take control. Sometimes it really works out beautifully and people get amazing health outcomes, and that’s the way it should be.

Hey Dr. Palmer, that’s a very good place to stop, and so we’re going to stop with that. Thank you very much for taking my questions and walking everyone through that. Congratulations on the new gift, and I’m very much looking forward to seeing what happens with your center.

Please don’t hesitate to stay in touch and let me know whenever you come across something that you think is new and particularly compelling.

I mean this is a ridic — I mean, I’ve seen literally hundreds of people on my tour now who’ve come up to me in the meet and greets afterwards and have said, “You know, I’ve lost 150 pounds in the last 10 months; people told me that was impossible; I’ve got my life back; my psychiatric disorders are in remission.”

I'm wondering, maybe this is a closing thought: tell me what you think about this, because I think we’re at this point and I think this is perhaps what you’re pointing out. My sense is that with the really severe mental disorders—so intractable depression, especially in the absence of life circumstances that would point in that direction, manic depressive disorder, the serious psychosis—that as mental health professionals, as physicians, our primary assumption at the moment should be that these are metabolic-related or other physiological disorders until there is compelling proof otherwise.

100%. I am firmly committed to that; and again, there are decades of science to confirm this. The neuroimaging studies, all of the genetic studies — when they look at the genes that increase risk for schizophrenia or bipolar disorder and when they look at what do these genes do, guess where they converge? Metabolism and mitochondria.

It’s not dopamine; it’s not serotonin; it’s metabolism and mitochondria. And in many ways, this is a game changer. And the reason it’s so important is because there are solutions available today, like dietary strategies that people can implement.

We don’t have to wait 50 years for some novel treatment to work its way through the development and review process with the FDA. We don't need to wait; we've got things we can do today.

All right, sir, well, I’m going to continue my discussion with Dr. Palmer on The Daily Wire Plus side of the interview, dividing line, let’s say.

And so I want to find out from him a bit more about what shaped his interest in the medical community, in medical practice. I want to find out why he focused on mental health. I want to see what his vision is for his new center into the future, and so on.

If you’re inclined to join us for that additional half an hour, please feel invited and welcome to do so. Thank you very much to the film crew here, and are you in Massachusetts? Are you in Boston today?

I am in Arlington, Mass., and I understand you’re in Arlington — my old hometown!

Yes, your old hometown, my own town!

Yeah, yeah, so that’s great!

All right, all right. So thank you to the film crew here up in Northern Ontario as well, and thank you to everyone who's watching and listening; your time and attention is much appreciated.

Thank you very much, sir! Thank you!