Transform Your Mental Health With Diet & Lifestyle

00:00:00.000 | Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life.

00:00:05.700 | I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine.

00:00:14.700 | My guest today is Dr. Chris Palmer.

00:00:16.840 | Dr. Chris Palmer is a psychiatrist and researcher at Harvard University.

00:00:21.020 | He focuses on how metabolic health, and mitochondrial health in particular,

00:00:25.500 | can be leveraged to treat, and in some cases cure, psychiatric disorders, including schizophrenia, autism, depression, bipolar, and ADHD.

00:00:34.220 | Today, we discuss how metabolic health, something we hear a lot about nowadays, is really about mitochondrial health

00:00:40.400 | and the specific lifestyle and other factors that you can use to improve mitochondrial number and function.

00:00:45.940 | We talk about things like exercise, sleep, sunlight, which you've heard about before,

00:00:50.120 | but we talk about those from a different perspective,

00:00:52.380 | and we discuss some things that have never been discussed before on this podcast,

00:00:56.160 | at least in light of mitochondrial health, things such as creatine, methylene blue, nicotine,

00:01:02.000 | and we talk about the key role of specific B vitamins and iron in brain function.

00:01:06.220 | We also have a very direct discussion about vaccines and whether or not inflammation caused by vaccines

00:01:11.500 | can potentially damage mitochondria, which then leads to mental health challenges.

00:01:15.460 | And of course, in that context, we discuss the vaccine autism debate.

00:01:19.700 | We also discuss public health and what is needed to truly change the way people exercise and eat

00:01:24.600 | and the rapidly changing landscape of the National Institutes of Health and the CDC.

00:01:28.540 | As you'll soon hear, Dr. Palmer gives us a master class on mitochondrial function

00:01:33.600 | and how to improve this vital aspect of our health.

00:01:36.080 | If you've heard about metabolic health, you've heard about the obesity crisis, that's important,

00:01:40.340 | but looking at all of that and approaching it through the lens of mitochondrial health,

00:01:44.760 | you'll soon learn is absolutely the way to go.

00:01:47.520 | It's a new perspective that will change the way that you think about mental and physical health

00:01:51.540 | and that no doubt will impact your health practices in very positive ways.

00:01:55.660 | Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford.

00:02:00.880 | It is, however, part of my desire and effort to bring zero cost to consumer information about science

00:02:05.920 | and science-related tools to the general public.

00:02:08.340 | In keeping with that theme, this episode does include sponsors.

00:02:11.700 | And now for my discussion with Dr. Chris Palmer.

00:02:15.140 | Dr. Chris Palmer, welcome back.

00:02:18.120 | Thank you so much for having me back.

00:02:20.260 | I credit you with leading the call to arms, the public awareness, and the implementation of what some people call metabolic psychiatry,

00:02:30.820 | but what we could easily just call the relationship between mental and physical health

00:02:36.740 | and the use of nutrition, supplementation, and where appropriate, prescription drugs for the treatment of mental health.

00:02:45.420 | But what do you call this field that you've basically founded and that you're pioneering?

00:02:51.020 | There are others, right, but that you're pioneering.

00:02:54.260 | And how should the general public think about the relationship between mitochondria and their mental health?

00:02:59.900 | For those that are not aware, educate us.

00:03:03.260 | I could talk for hours on this.

00:03:05.540 | So first of all, thank you for – I think you're actually giving me way too much credit, though.

00:03:12.040 | I don't know about that.

00:03:14.480 | I'm talking a lot about it, and I think I will accept that maybe I'm able to talk about it in a way that helps people understand it,

00:03:22.660 | that other scientists haven't been able to.

00:03:25.180 | But, you know, one of the more important reasons I want to say this is because, unbeknownst to a lot of people,

00:03:33.900 | this field has actually been around for about a century and a half.

00:03:39.220 | Researchers in the 1800s, around the turn of the century, well up into the 1960s, were hyper-focused on the role of metabolism in severe mental illness.

00:03:50.940 | Schizophrenia, bipolar disorder, they were actually measuring levels of lactate and glucose and other kind of metabolic biomarkers in people with schizophrenia and bipolar disorder,

00:04:03.020 | documenting differences, really kind of honing in on these metabolic disruptions is potentially the cause of mental illness.

00:04:14.720 | And then our field lost its way.

00:04:17.380 | We became focused on neurotransmitters and assumed that they were the primary cause of mental illness,

00:04:25.960 | while other fields were focused on psychological and social factors.

00:04:31.560 | You know, we got cognitive behavioral therapy, we still had psychodynamic psychotherapy,

00:04:36.000 | but people were doing research on adverse childhood experiences.

00:04:40.520 | That was really taking off, documenting that that's related.

00:04:44.340 | And so, you know, the field kind of splintered into these biological, psychological, social camps.

00:04:52.920 | And people really hyper-focused in all of these ways.

00:04:56.640 | To me, this field of integrating metabolism with mental health, with physical health,

00:05:06.740 | is about unifying that whole story.

00:05:11.280 | It's about unifying and building on what these researchers a hundred years ago were pursuing.

00:05:20.080 | It's about integrating the biological, psychological, and social camps.

00:05:24.660 | It's about putting it all together and stop being so reductionistic and simplistic

00:05:31.300 | to suggest that it's all biological or it's all psychological or it's all social,

00:05:36.320 | and that if it's one, it can't be the other.

00:05:39.160 | It can be all of them.

00:05:40.400 | And it's different combinations for different people.

00:05:44.940 | So, in many ways, I'm just standing on the shoulders of giants who have done groundbreaking work

00:05:54.100 | to create the science that allows us to put this all together.

00:05:57.700 | With that said, I do firmly believe that we are on the cusp of a revolutionary change

00:06:09.380 | in the paradigm of the mental health field, of how we think about mental illness.

00:06:15.540 | You know, there are myriad biological things.

00:06:21.120 | The psychological and social things are all obvious and true.

00:06:25.440 | Yes, stress, trauma, loneliness, adverse childhood experiences, all of those things come together.

00:06:32.600 | Our field is long known that all of those things play a role in mental illness.

00:06:36.220 | Exactly which mental illnesses?

00:06:38.640 | It's essentially all of them.

00:06:40.420 | Every one of the labels in DSM-5 can be impacted by biological, psychological, and social factors.

00:06:49.680 | So, trauma and childhood increases risk for post-traumatic stress disorder.

00:06:54.920 | Duh.

00:06:55.740 | Everybody knows that.

00:06:56.840 | Trauma and childhood also increases risk for neurodevelopmental disorders if it occurs early enough.

00:07:04.320 | It increases risk for substance use disorders, personality disorders, psychotic disorders,

00:07:10.440 | mood disorders, anxiety disorders, dementia later in life, and everything else.

00:07:16.860 | Every label.

00:07:19.580 | What else do adverse childhood experiences increase risk for?

00:07:23.000 | All of the metabolic disorders.

00:07:25.560 | Obesity, type 2 diabetes, cardiovascular disease, autoimmune disorders, premature mortality.

00:07:32.420 | You know, we have statistics that, just sticking with that theme, adverse childhood experiences.

00:07:39.140 | If you have six or more adverse childhood experiences, compared to somebody who has no adverse childhood experiences,

00:07:47.780 | Now, that's a rare group, granted.

00:07:50.060 | But for the people who have six or more, on average, they live 20 years shorter.

00:07:57.180 | They lose 20 years of life because of those adverse childhood experiences.

00:08:05.080 | And so, is that a mental health issue?

00:08:07.500 | I would say it's a physical health issue.

00:08:09.780 | It's both.

00:08:11.540 | It's both a mental health issue and a physical health issue.

00:08:14.360 | And so, how can we understand that?

00:08:15.820 | How can we understand that trauma in childhood increases risk for heart disease, and obesity, and diabetes, and dementia, and PTSD, and ADHD, and ADHD, and substance use disorders,

00:08:30.340 | And the only way to connect it is through metabolism, and ultimately through mitochondria.

00:08:37.840 | Unfortunately, people like simple answers, and they're like, so diet will fix everything.

00:08:43.140 | I'm like, no, I never said diet will fix everything.

00:08:45.260 | But it can help.

00:08:46.620 | And it can be life-changing and life-saving.

00:08:51.740 | I don't want to minimize or step back from my work with dietary interventions.

00:08:59.440 | There is no doubt in my mind it can dramatically change people's lives.

00:09:06.480 | But it's not just diet.

00:09:08.760 | It's lots of other things.

00:09:10.900 | And so, it's putting it together and trying to make sense of the science for what does cardiovascular disease have to do with depression or PTSD.

00:09:21.180 | On the surface, a lot of people scratch their heads, and they really don't know.

00:09:26.320 | They assume that, well, one's a brain disorder and one's a heart disorder.

00:09:30.320 | And it's like, no, we need to integrate that because all of the risk factors, essentially the same biopsychosocial risk factors that increase risk for heart disease also increase risk for brain disease.

00:09:45.720 | And we need to start putting it together.

00:09:48.760 | We need to be more sophisticated.

00:09:50.100 | We have computers.

00:09:51.380 | We have AI.

00:09:52.060 | It's 2025.

00:09:52.780 | We can do better.

00:09:54.740 | Yes, well, first of all, I, and I'm sure the listeners, really appreciate your humility regarding who's responsible for the big surge in the interest in this field.

00:10:05.640 | So, thanks for crediting your predecessors and the others in the field.

00:10:10.300 | At the same time, I credit you with really popularizing a lot of these terms, being willing to go public-facing and share about metabolic psychiatry, for lack of a better way to put it, metabolic psychiatry.

00:10:24.720 | And really championing these ideas and being open to being part of a medical and science and public discourse community.

00:10:33.980 | So, I'd be remiss if I didn't say that.

00:10:36.840 | So, hopefully you'll take that in.

00:10:38.060 | And if you won't, then-

00:10:39.400 | I very much appreciate it.

00:10:40.960 | Well, it's true.

00:10:41.860 | Thank you very much.

00:10:42.600 | It's true.

00:10:43.040 | And I'm not alone in that sentiment.

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00:13:44.720 | If I think about a mental health condition like depression, let's take depression to start off.

00:13:52.580 | I can just broadly create two, you know, columns of things or approaches that one might take.

00:14:01.900 | One is this mental model of sort of a molecule deficiency.

00:14:06.460 | Like, I'm not saying this, but there are many who at one point thought depression is related to a deficiency in serotonin,

00:14:14.680 | or depression is related to a deficiency in dopamine, either levels, regulation, enzymatic control,

00:14:21.720 | whatever the level of control.

00:14:25.340 | Just this idea that these molecules are somehow lacking, if you put them back, you can relieve some symptoms of depression.

00:14:33.580 | The other column that comes to mind for me, having looked at the data on cognitive behavioral therapy,

00:14:41.900 | on the data on psychedelics in the clinical setting for the treatment of depression, SSRIs, and other so-called antidepressants,

00:14:50.700 | is this notion of neuroplasticity, the idea that neural circuits can change,

00:14:54.400 | and that neural circuits control our sense of well-being, our perception of self, perception of others, feelings of agency, et cetera.

00:15:01.000 | And it's now very clear that if you change levels of neuromodulators, like dopamine, like serotonin,

00:15:07.520 | you don't necessarily cure depression, but you open a window for plasticity,

00:15:15.100 | and then perhaps the therapy that you're doing can modify brain circuits more robustly.

00:15:19.680 | So I think in terms of molecule deficiency, maybe it's a vitamin deficiency, a neuromodulator deficiency,

00:15:25.340 | and then I also think about plasticity, that these treatments are just allowing for more brain change,

00:15:30.820 | more rapidly.

00:15:31.400 | What other columns would you add to that picture?

00:15:35.040 | And perhaps first, do you think that picture is woefully inadequate or just partially inadequate?

00:15:43.440 | Because I think this is the way most people think about the treatment of mental health.

00:15:46.920 | They think, oh, there's something missing.

00:15:48.100 | You take a drug and you get that thing back.

00:15:50.400 | And then like ADHD, you don't have enough dopamine or you put it in,

00:15:54.960 | and then all of a sudden attentional circuits work better.

00:15:56.940 | This kind of thing versus plasticity, which is the modification of those circuits.

00:16:01.820 | And the two things are not mutually exclusive, but I think until now there really hasn't been a clear understanding

00:16:08.920 | that there are other columns for mechanistic change in mental health.

00:16:14.240 | I would say the concept of metabolism, metabolic regulation, mitochondrial function, mitochondrial health,

00:16:26.240 | actually is an umbrella concept for everything you've just said.

00:16:32.160 | It's an umbrella concept for, well, how do we create neurotransmitters?

00:16:37.700 | Where do these neurotransmitters come from?

00:16:39.760 | What regulates their production, release from cells?

00:16:45.020 | And then even to go further, what impact do those neurotransmitters have on other cells?

00:16:51.600 | They are largely regulating brain metabolism.

00:16:56.520 | And the way we usually think about it is they are regulating brain activity.

00:17:02.540 | But if you ask the question, well, what is brain activity?

00:17:05.760 | Brain activity is either, it's fueled by metabolism.

00:17:10.940 | A neuron cannot be active unless it has the capacity to increase its ATP kind of production.

00:17:21.640 | And then when you suppress a neuron, when you inhibit its function, the ATP production goes down.

00:17:30.860 | So whether you want to think of metabolism as just a consequence of neural activity,

00:17:34.840 | I actually think about it as an integral part of neural activity.

00:17:39.300 | It's kind of like your car can't go without the engine.

00:17:43.260 | A cell can't go without mitochondria.

00:17:46.940 | A cell can't do what it's supposed to do without mitochondria.

00:17:50.700 | The other concept that you mentioned, neuroplasticity.

00:17:54.020 | Neuroplasticity is all about energy and metabolic resources to create new connections.

00:18:02.580 | New neural connections between axons, dendrites, somas, other aspects of neurons and cells and other types of cells, astrocytes, oligodendrocytes.

00:18:19.180 | But in order to get neuroplasticity, neuroplasticity implies growth and modulation and even pruning.

00:18:27.880 | But it involves change.

00:18:29.860 | And in order for a living organism to change, that requires this foundational concept of metabolism.

00:18:40.060 | Now, on the surface, to a lot of people, that sounds too abstract.

00:18:43.160 | And it sounds like, well, that's ridiculous then.

00:18:45.300 | If you're saying that metabolism is everything in biology.

00:18:48.080 | And I kind of am.

00:18:48.960 | Of course it is.

00:18:49.760 | You can't talk about biology without talking about metabolism.

00:18:54.340 | But when you talk about metabolic health, it becomes much more concrete, pragmatic, and real with real tools that you talk about all of the time on this podcast.

00:19:10.700 | Exercise promotes metabolic health.

00:19:15.840 | Exercise promotes neuroplasticity.

00:19:21.180 | They are inseparable.

00:19:22.800 | You can't improve your metabolic health without also at least opening up the opportunity for neuroplasticity.

00:19:31.680 | Improving your diet does the same thing.

00:19:35.880 | Sleep or lack thereof can impact this.

00:19:40.500 | Substance use can impact this.

00:19:44.280 | And so, you know, in a way, it basically says, let's connect all of the dots.

00:19:49.960 | Let's not hyper-focus on serotonin and a serotonin imbalance or deficiency as the singular cause of depression.

00:19:57.840 | Because for those of you who don't know, that is ridiculously reductionistic.

00:20:04.260 | And it is absolutely not true.

00:20:08.500 | We know that.

00:20:09.220 | We know that with certainty now.

00:20:10.980 | You know, the whole serotonin hypothesis of depression came about not because researchers identified serotonin deficits in the brain.

00:20:25.000 | That entire concept came from the observation that medications that modulate serotonin activity or inhibit its reuptake into neurons,

00:20:40.340 | those medications, SSRIs, other types of antidepressants, those medications can reduce the symptoms of depression in some people.

00:20:51.620 | That was just a purely serendipitous finding.

00:20:58.160 | It was serendipity.

00:21:01.440 | The first antidepressant was actually a tuberculosis treatment.

00:21:05.800 | They were giving it to patients on a tuberculosis ward.

00:21:11.460 | And an astute infectious disease doctor noticed some of these patients are really depressed.

00:21:18.980 | But when I give them this tuberculosis treatment, they perk up.

00:21:24.860 | Within a few weeks, they start looking a lot less depressed.

00:21:28.580 | And I don't think it's a coincidence.

00:21:30.840 | I think it's the medication I'm giving them.

00:21:33.600 | Do you recall what the drug was?

00:21:35.680 | It's the first MAO inhibitor.

00:21:38.200 | And I could be saying the name wrong, but it's the first MAO inhibitor.

00:21:42.740 | And that became the first antidepressant.

00:21:48.380 | Which makes sense.

00:21:50.460 | MAO inhibitors inhibit the enzymes that break down.

00:21:55.240 | Or let's just speak about these enzymes broadly.

00:21:57.400 | I think most antidepressant drugs or treatments for ADHD, typical prescription treatments, either reduce the breakdown of neuromodulators like serotonin, dopamine, acetylcholine, depending on which one we're talking about.

00:22:11.200 | Or they reduce the reuptake so that there's just more neuromodulator around for longer.

00:22:19.380 | Tell us about mitochondria in the framework of mental health.

00:22:24.500 | So most people know mitochondria as the powerhouse of the cell, if they know it at all.

00:22:29.780 | So these tiny little organelles.

00:22:32.120 | And the powerhouse of the cell reference means that mitochondria take the breakdown products of the food that we're eating.

00:22:42.020 | They are the primary thing using the oxygen that we're breathing in.

00:22:46.920 | They are creating the carbon dioxide that we're breathing out.

00:22:50.600 | And that they are turning food into ATP, which is the energy currency of the cell.

00:22:56.940 | So they're taking food and oxygen and lots of other things.

00:23:00.960 | But let's just simplify.

00:23:02.320 | Food and oxygen, converting it into ATP.

00:23:06.840 | And that is what the powerhouse of the cell kind of refers to.

00:23:11.320 | There is no doubt they do that.

00:23:13.700 | There is no doubt that when that process stops, humans have about six minutes or so, and then we're dead.

00:23:20.900 | That process is critical to life.

00:23:26.160 | There is no other process in the human body that you can disrupt that will kill the organism faster.

00:23:33.520 | It is central to living organisms, this production of ATP.

00:23:38.980 | So I don't at all mean to take away or minimize that function.

00:23:44.460 | But research over the last 25 years has completely upended that simplistic notion of what mitochondria are doing.

00:23:52.880 | They are actually doing so much more.

00:23:55.740 | Some people have created the reference that mitochondria are like the workers inside a cell.

00:24:00.780 | That in order for a cell to work, you need a workforce.

00:24:05.260 | Because there's so much that needs to be done.

00:24:08.000 | Signals need to be sent.

00:24:10.200 | Like all this work, all of these different things need to be functioning.

00:24:15.740 | And mitochondria are absolutely providing the energy for those things to happen.

00:24:21.360 | But they're also orchestrating a lot of it.

00:24:24.460 | So for example, they play a direct role in converting food into some of the substrates for the production of neurotransmitters.

00:24:34.140 | And that plays a role in GABA in GABA's release from a neuron.

00:24:48.180 | They actually go to the cell membrane and move along the membrane, dispensing vesicles of neurotransmitters.

00:24:59.420 | And when you take the mitochondria away from the synapse, but provide that synapse with ATP, vesicles don't get released.

00:25:12.900 | Those neurotransmitters aren't getting released.

00:25:14.500 | The mitochondria are doing more.

00:25:16.500 | We don't exactly know what.

00:25:18.580 | But they're doing more than just providing the energy.

00:25:21.720 | They play a role in turning inflammation and immune cells both on and off.

00:25:30.620 | They play an instrumental role in both the first and the last step in the synthesis of cortisol.

00:25:49.660 | And they play a role in the first step in the synthesis of all of the steroid hormones, which include estrogen, testosterone, progesterone.

00:25:58.460 | So that if you have dysregulation of testosterone or estrogen or progesterone, you must understand the role of mitochondria in that dysregulation because they are critical in the production and release of these hormones.

00:26:21.040 | They are the primary regulator of epigenetics.

00:26:26.460 | So epigenetics are the expression of genes from the cell nucleus.

00:26:30.700 | And researchers have long known that that's related to levels of reactive oxygen species.

00:26:36.140 | It's related to levels of calcium.

00:26:39.200 | It's related to other cell signals.

00:26:41.520 | Those cell signals are mostly originating within mitochondria during the development of any cell.

00:26:48.880 | Mitochondria, they are like a universe unto themselves.

00:26:53.180 | And there's so much we don't know about them.

00:26:55.020 | But what researchers have found is that mitochondria actually line up, literally line up in an organized fashion around the cell nucleus and take on different conformations.

00:27:08.700 | And that is somehow sending signals to the genes to result in the expression or the suppression of different genes from the nucleus.

00:27:22.320 | And that when researchers take these mitochondria and like mess them up or something, the cell doesn't develop normally.

00:27:29.480 | You know, they've been implicated in all of the phases of the human stress response to psychological stress.

00:27:37.560 | So that includes cortisol release, noradrenaline release.

00:27:42.580 | It includes inflammation.

00:27:44.800 | And it includes epigenetic changes.

00:27:48.000 | So those are kind of the four buckets of the human stress response.

00:27:52.320 | Cortisol, adrenaline, inflammation, and epigenetic changes.

00:27:59.840 | And researchers actually manipulated mitochondrial genes, two genes in the cell nucleus that control for mitochondrial proteins and two genes in mitochondria themselves.

00:28:12.520 | And by manipulating these four different genes, one at a time in mice, they could impact all of the four aspects of the stress response.

00:28:25.660 | And so what that means is that mitochondria are somehow involved in regulating the human stress response.

00:28:33.740 | And so the way that I think about it is that, and the way that many researchers actually think about it now,

00:28:43.140 | is that mitochondria, you know, there are hundreds, sometimes thousands of them in our cells, in each of our cells.

00:28:53.020 | Most neurons have thousands of mitochondria.

00:28:56.640 | The mitochondria are actually moving around.

00:29:00.020 | They use the cytoskeleton to move around the cell.

00:29:03.620 | They fuse with each other.

00:29:05.220 | It's called mitochondrial dynamics.

00:29:09.260 | They, like, change shape.

00:29:11.360 | They do all sorts of things.

00:29:12.880 | And again, that impacts all of these signaling processes.

00:29:16.980 | But that's just within one little cell.

00:29:19.900 | So you can think of one cell as, like, almost a village of mitochondria.

00:29:25.220 | That they're all just doing different things and working together to help that cell function.

00:29:31.180 | But in fact, when you think about hormones like cortisol,

00:29:36.040 | you can think about it as a way for mitochondria in one cell to produce cortisol,

00:29:41.240 | that they can get sent to mitochondria in another cell to make that other cell do something,

00:29:47.340 | to either increase its activity or decrease its activity.

00:29:52.380 | Some people actually think about human cells as just a network of mitochondria.

00:29:58.440 | All kind of mitochondria throughout the body and brain are just doing all sorts of things.

00:30:07.840 | And at the end of the day, we come back to just common sense.

00:30:12.040 | At the end of the day, it's about helping the organism adapt and survive.

00:30:16.020 | Ultimately, organisms, rule number one, they need to survive.

00:30:22.560 | Rule number two, they need to reproduce.

00:30:25.960 | And rule number three, they need to adapt.

00:30:30.200 | And mitochondria are playing a foundational role in all of those basic aspects of organismal survival.

00:30:39.900 | And again, to some people, well, that's so high level.

00:30:44.060 | That's like what you're saying.

00:30:45.360 | It's everything.

00:30:45.920 | I'm like, yeah, it kind of is.

00:30:47.840 | And mental health falls under it.

00:30:50.320 | How could we think about mental health without thinking about the big picture?

00:30:54.680 | Let's start with the big picture, and then let's put health into it.

00:31:00.480 | And let's put the lack of adaptation, or the lack of survival, or these other things.

00:31:08.700 | I'd like to take a quick break and thank our sponsor, AG1.

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00:33:59.480 | What are some of the things that we know can improve mitochondrial health, either number, function, or otherwise?

00:34:07.700 | And maybe we can talk about the basics first and get a little bit granular, if you could, about, you know,

00:34:13.160 | what are the prescriptions for keeping your mitochondria healthy or improving your mitochondrial number and improving their function?

00:34:18.800 | And then we can transition from there to the more, let's just say, the more advanced ways of doing that.

00:34:28.160 | Is there a role for supplementation?

00:34:30.820 | Is there a role for drugs?

00:34:32.440 | Is there, you know, these days where I hear about urolithin A, because I'm a little bit of an adventurer these days,

00:34:38.340 | and I'm turning 50 later this year, I decided to experiment with a peptide that is SR31,

00:34:44.160 | which is specifically to improve mitochondrial function.

00:34:46.880 | And I'm doing this with the full understanding.

00:34:49.120 | It may do nothing or it may kill me.

00:34:50.580 | I don't know.

00:34:51.080 | But we'll find out.

00:34:52.500 | But someone had to do it.

00:34:54.420 | And I'm a one variable at a time kind of guy.

00:34:57.660 | So it was important for me to stay with my current regimen and only change that, do blood work, et cetera,

00:35:04.960 | because a lot of people, some people out there are more in the mode of trying to do a bunch of things.

00:35:10.620 | And I don't think that's as helpful to me.

00:35:12.740 | It's also just not.

00:35:13.760 | It's not in keeping with my nature.

00:35:15.660 | You're a scientist.

00:35:15.860 | I'm a scientist.

00:35:16.280 | One variable at a time.

00:35:17.340 | You're a scientist.

00:35:17.340 | That is great.

00:35:18.000 | That's right.

00:35:18.240 | I'm monogamous with respect to variables.

00:35:20.180 | Right.

00:35:20.760 | So what can we do at a basic level to keep and improve our mitochondrial number and function?

00:35:27.380 | And if we have to hit on some of the usual suspects, fine.

00:35:30.600 | But if you could tell us how we can do this.

00:35:34.540 | So I'm really going to start with the basics and they're going to sound cliche and they're going to sound too basic to most people.

00:35:41.700 | And I just want to set the stage for even for severe mental illness.

00:35:46.760 | We can talk about strategies that will work.

00:35:49.500 | And these strategies that I'm going to describe are not really appropriate.

00:35:53.520 | Like when somebody becomes severely ill, these strategies may not be sufficient.

00:35:58.500 | But the basics are what we call the field of lifestyle medicine.

00:36:03.200 | So there are six pillars of lifestyle medicine.

00:36:06.660 | They include diet, nutrition, exercise or movement, sleep, managing substance use, ideally reducing it or minimizing it or eliminating it, stress reduction practices, mindfulness, meditation, yoga.

00:36:28.760 | And the last one is relationships.

00:36:32.140 | I throw in the word purpose into relationships because I think even if you don't have a lot of friends or family, you can still have a very full thriving life if you have a purpose.

00:36:46.240 | So those are the six pillars.

00:36:48.520 | Unfortunately, this is where the cliches and the worthless advice begin, especially in the diet nutrition camp.

00:36:57.620 | Because people will say, eat more plants, eat some broccoli, have some good blueberries.

00:37:02.700 | Blueberries have antioxidants.

00:37:04.180 | Have some blueberries on whatever else you're eating and everything will be fine.

00:37:11.020 | If you just add a couple of servings of blueberries a week, you'll improve your health.

00:37:16.840 | Brain food.

00:37:17.740 | And it is such worthless advice.

00:37:20.540 | It is not at all that simple.

00:37:23.040 | And so I think diet nutrition gets complicated fast.

00:37:29.300 | The other things are actually pretty straightforward.

00:37:32.000 | Should you move your body?

00:37:34.540 | Yes.

00:37:35.040 | Should you stress your body intermittently, allowing for full recovery?

00:37:45.380 | Yes.

00:37:45.680 | That's what most people call exercise.

00:37:47.480 | And what are you doing when you exercise?

00:37:50.320 | You're actually, if we look at like the muscles, for example, muscle tissue, what exactly does exercise do?

00:37:58.800 | Whether it's isometric exercise to increase the size of the muscle, or whether it's endurance capacity, which actually does not change the size of the muscle at all, but allows for somebody to run longer, faster, harder.

00:38:16.280 | So marathon runners, for example, can be quite thin.

00:38:19.020 | You can look at a marathon runner and think you're not even an athlete.

00:38:22.000 | They don't look all that different, yet they can run sometimes a hundred miles.

00:38:28.840 | And what makes their muscles different than my muscles?

00:38:33.440 | Because I can't run a hundred miles.

00:38:34.640 | Me either.

00:38:35.100 | What makes their muscles different than mine?

00:38:38.700 | Even if the size isn't different, there is one and only one thing that makes their muscles different, and it's called mitochondria.

00:38:44.260 | The number?

00:38:44.960 | The number of mitochondria, and almost certainly the health of mitochondria.

00:38:49.020 | You can actually take a biopsy of their muscle, and you will see a much higher density of mitochondria in their muscle tissue than you will in mine.

00:38:57.160 | If you actually then did a more thorough assessment of ATP capacity, their muscles or their mitochondria would be much healthier than mine.

00:39:08.660 | Their mitochondria would have greater capacity for ATP production than my mitochondria would.

00:39:15.040 | So that's exercise.

00:39:17.760 | There are lots of things you can do with exercise.

00:39:20.260 | For people who don't exercise at all, yes, get out and just walk.

00:39:23.640 | Just do something.

00:39:24.800 | Maybe get some sunlight in the morning while you're at it.

00:39:28.060 | That sounds like a good idea.

00:39:29.360 | The substance use is obvious.

00:39:35.960 | It's the thing.

00:39:36.520 | You've been talking about it.

00:39:37.640 | I've been talking about it.

00:39:38.620 | Which substances deplete mitochondria?

00:39:40.520 | I've been very interested in this.

00:39:41.880 | I'm a big lover of certain genres of music, and whenever the topic of music comes up, the name Rick Rubin comes up because he's been on this podcast twice.

00:39:54.020 | He's the famous Rick Rubin, amazing producer, and I'm blessed to have him as a close friend.

00:39:58.280 | And I often ask Rick, I'm like, why are so many of these folks in music dead?

00:40:04.300 | There seems to be a history of people who did stimulants.

00:40:10.440 | It took a lot of stimulants, cocaine and amphetamine in particular.

00:40:13.660 | Musicians that did that in the 70s and 80s and 90s seemed to drop dead of heart attacks later when they were not currently using, as far as we know, those stimulants.

00:40:26.980 | Is it the case that stimulants like cocaine and amphetamine deplete cells of mitochondria?

00:40:34.500 | Do we know that to be true?

00:40:36.240 | We do know, and it's a slightly more complex story.

00:40:40.760 | So it's all about the dose.

00:40:43.060 | So stimulants are used to treat ADHD.

00:40:48.180 | And we know that people, we've known for decades, people who have ADHD, who have symptoms of ADHD, have glucose hypometabolism in their brains.

00:41:00.240 | So their brains are not producing enough ATP from glucose.

00:41:06.740 | What is one way to increase that?

00:41:09.600 | Dopamine.

00:41:10.820 | Dopamine will increase that so you can give people stimulants to improve their brain metabolism enough so that they now no longer have symptoms or at least have a reduction in their symptoms.

00:41:26.320 | That story is unequivocally true.

00:41:29.360 | We have lots of animal data, human neuroimaging data, clinical research studies documenting that appropriate doses of stimulants, so that's usually low-ish doses, can improve brain metabolism.

00:41:47.420 | And what that means is that they're actually stimulating mitochondria to produce more ATP.

00:41:52.520 | However, metabolism is all about balance.

00:41:58.980 | You can underdo it, you can underdo it, and you can overdo it.

00:42:01.760 | And when you overdo it, what happens is that if you hyper-stimulate mitochondria with high doses of stimulants, the mitochondria are essentially running on all cylinders, and electrons start leaking out of the electron transport chain.

00:42:20.720 | And what happens is then damage the mitochondria with high doses of stimulants, and it can lead to chronic mitochondria, chronic metabolic dysfunction, which then damage the mitochondria themselves and damage other aspects of the cell.

00:42:31.500 | And it can lead to chronic mitochondrial dysfunction, chronic metabolic dysfunction.

00:42:39.500 | It's challenging with stimulants.

00:42:42.280 | Because people are looking for a yes or no answer.

00:42:44.700 | So, Dr. Palmer, do you think stimulants are good or bad?

00:42:47.860 | I don't have an answer to that.

00:42:50.720 | It depends on the person.

00:42:52.300 | It depends on the dose of stimulants.

00:42:54.180 | It depends on the type of stimulant.

00:42:56.900 | It depends on what impact it's having on that person.

00:43:00.180 | But we need to open our minds to the possibility that, yes, maybe some people do benefit from stimulants.

00:43:07.780 | And maybe, at the same time, other people are harmed in catastrophic ways by stimulants.

00:43:14.880 | And it can all be linked through mitochondrial mechanisms.

00:43:20.820 | It can certainly be linked through dopamine.

00:43:22.660 | But, again, we have to ask, well, what is that dopamine doing to the target cells?

00:43:28.140 | That when dopamine gets released and connects with a dopamine receptor, what happens to that target cell, it changes the metabolism of that target cell.

00:43:41.280 | It increases the activity of that target cell.

00:43:44.260 | So, stimulants are one.

00:43:46.200 | Back to this bigger kind of lifestyle medicine picture.

00:43:49.720 | Stimulants are definitely one.

00:43:51.500 | High-dose stimulants, very harmful to human health.

00:43:54.400 | What are some others?

00:43:55.960 | Alcohol.

00:43:56.560 | We've known since the 1960s.

00:44:00.160 | In the 1960s, researchers were trying to figure out, how the hell does alcohol cause cirrhosis?

00:44:06.340 | We knew that.

00:44:08.960 | We've known that.

00:44:09.880 | We've known that for a long time.

00:44:11.800 | Alcoholics develop liver failure.

00:44:14.780 | They develop cirrhosis of the liver, and they can die from it.

00:44:18.820 | How exactly does that happen?

00:44:22.380 | In the 1960s, researchers figured out it's mitochondrial toxicity.

00:44:27.440 | Interesting.

00:44:28.300 | In the liver cells.

00:44:29.660 | That is what's making the liver cells die.

00:44:32.000 | That alcohol gets converted into this molecule called acetaldehyde, which is very toxic to lots of cell parts, but in particular to mitochondria.

00:44:45.000 | Mitochondria are processing this alcohol and other enzymes and kind of other things are trying to detoxify the alcohol.

00:44:54.480 | But at the end of the day, mitochondrial toxicity seems to be a clear route.

00:45:00.740 | When I was doing research on mitochondria for the book, there were over 10,000 published research articles of alcohol and mitochondria.

00:45:15.260 | And I was initially shocked by that, and I wondered, like, what's that about?

00:45:20.440 | Like, that's how I know this 1960s story and everything else is because researchers have been looking at how is it that alcohol can be so toxic?

00:45:31.520 | And the two organs that are most effective are the liver, because that's the primary organ trying to detoxify it, and then the brain.

00:45:40.640 | And why the brain?

00:45:42.200 | Because the brain is highly sensitive to metabolic disruption.

00:45:46.080 | Other substances of abuse, tobacco, the carcinogens in tobacco.

00:45:54.480 | So not nicotine per se.

00:45:55.840 | Do we know if nicotine is depleting mitochondria?

00:45:59.160 | Nicotine is a stimulant for mitochondria.

00:46:02.140 | So again, similar story.

00:46:03.960 | Low doses can be great.

00:46:06.760 | High doses may, in fact, be toxic.

00:46:09.340 | Oh, good.

00:46:09.920 | You've got to get – you've got to find the right balance.

00:46:12.800 | I'm not a big nicotine guy, but lately I've started chewing half of a piece of nicotine gum a few times a week.

00:46:22.460 | So two milligrams to four milligrams, which is very low dose.

00:46:25.840 | A couple of – I would say maybe three, four days a week I'll do that.

00:46:31.280 | And I'm doing it specifically for brain health reasons.

00:46:35.500 | And I have no relationship to any nicotine pouch or gum or anything like that, so I want to be really, like, company.

00:46:40.880 | So I'm doing a little experiment.

00:46:42.920 | And, you know, it's an interesting stimulant because it relaxes you a little bit too.

00:46:47.360 | But I wouldn't want kids to start doing this or people in their 20s or 30s.

00:46:51.320 | Like I said, I'm approaching the fifth floor.

00:46:52.900 | I'm going to be 50 in September.

00:46:54.100 | And I want to do everything I can to hold on to the neurons I've got.

00:46:57.880 | So I think low-level stimulation of perhaps the mitochondria and other – certainly the acetylcholine system with nicotine is a good idea.

00:47:06.980 | But what I see is a lot of people who are taking these pouches that range from anywhere from three milligrams on the low-end dose side all the way up to eight milligrams.

00:47:15.120 | And it is very habit-forming.

00:47:17.940 | People start with one pouch or two pouches a day, and pretty soon they're doing a canister every day or two.

00:47:23.440 | So even the cost, it starts to be a big deal.

00:47:26.940 | But it's pretty incredible.

00:47:28.260 | It was on the Berkeley campus, and I went to a little convenience store near the Berkeley campus recently.

00:47:32.180 | This kid came in, and we started chatting.

00:47:33.920 | He was a podcast fan.

00:47:35.460 | We were chatting, and he was there to buy nicotine pouches.

00:47:39.140 | I said, how many of those do you go through a week?

00:47:40.760 | And he's like, seven or eight.

00:47:42.920 | I was like, really?

00:47:44.020 | He was an engineering student.

00:47:46.100 | But in my years in college, it was always just, you know, some coffee or something.

00:47:51.640 | Yeah, some coffee.

00:47:52.860 | We didn't really have.

00:47:53.780 | I'd stick with coffee.

00:47:54.740 | For the young folks, yeah.

00:47:56.860 | For the young folks?

00:47:57.600 | For the young.

00:47:57.880 | A little bit of coffee.

00:47:59.380 | And again, it's about dose.

00:48:01.280 | Yep.

00:48:01.520 | And it's about look.

00:48:04.160 | So most things that enhance metabolism quickly can be addictive.

00:48:14.760 | And I think that's the challenge for a lot of people, is that you get that energy right away.

00:48:23.660 | At some point, you acclimate to that substance somewhat, and then you want more.

00:48:32.220 | You want that same increase that you got before.

00:48:40.280 | So it's just important to kind of be mindful that you can overstimulate metabolism mitochondrial function.

00:48:49.760 | And then you start depleting mitochondria.

00:48:51.100 | And then, yeah.

00:48:53.100 | And then you actually, the mitochondria begin producing more reactive oxygen species, which

00:48:58.760 | ends up being detrimental.

00:48:59.820 | So it's like driving your car.

00:49:03.220 | Again, if you think about mitochondria like an engine, it's like an engine of your car.

00:49:09.660 | When you're driving your car on the highway, you don't want to go too slow, and you don't

00:49:15.520 | want to go too fast.

00:49:16.700 | You need to have balance.

00:49:18.180 | And acceleration is costly.

00:49:19.160 | And acceleration is costly, right?

00:49:21.060 | I mean, transmission systems, you know, create this incredible efficiency of being able to

00:49:25.920 | travel at speed with more efficiency, you know, but accelerating is a different thing altogether.

00:49:32.140 | I mean, that's the way that I think about it.

00:49:34.260 | And so somebody who's addicted to drugs and alcohol, for example, they're on a roller coaster

00:49:38.960 | ride of hyper-stimulating their metabolic rate and then trying to suppress that hyper-stimulation

00:49:46.800 | with sedatives so that they can sleep or calm down.

00:49:51.000 | And then they're just, but they're destroying their metabolic health.

00:49:56.160 | And does that really play out?

00:49:58.640 | Like, and is that, you know, some will say, well, Chris, that's just one of myriad things

00:50:03.120 | that they're doing to their cells.

00:50:04.780 | Sure.

00:50:05.360 | But does it play out in diseases that we think of as metabolic diseases?

00:50:10.980 | Absolutely.

00:50:12.780 | Type 2 diabetes?

00:50:15.200 | Yes.

00:50:15.860 | Cardiovascular disease?

00:50:17.480 | A hundred percent.

00:50:18.340 | Like premature mortality?

00:50:20.180 | Yeah.

00:50:20.820 | Um, like it, there's, it's kind of like the elephant in the room that we have just failed

00:50:27.980 | to look at because we've been so splintered with, no, it's biological.

00:50:34.240 | No, it's psychological.

00:50:35.200 | No, it's social.

00:50:36.040 | It's like, it's all of them.

00:50:37.200 | Let's look at the elephant that comprises all of them.

00:50:40.120 | One of the beautiful things about science is that you isolate variables.

00:50:44.400 | You can get very reductionist.

00:50:45.680 | We know that there are these things called mitochondria that they move around.

00:50:49.100 | I mean, these discoveries are truly incredible that have been made in the last hundred years

00:50:53.460 | or so.

00:50:53.880 | But there's been this, um, kind of obsession, I, I think in, in the public discussion around

00:51:00.920 | health that, you know, around things that are obviously related to the thing that you're

00:51:07.800 | trying to cure.

00:51:08.360 | So serotonin and brain health, it's like, oh, okay, it makes sense.

00:51:12.920 | You know, the listening to Prozac book came out, we increased serotonin, some people are

00:51:15.940 | feeling better.

00:51:16.500 | Maybe it's through neuroplasticity, maybe it's direct effects of serotonin and, but it makes

00:51:20.760 | sense.

00:51:21.060 | Serotonin brain, right?

00:51:22.640 | You know, um, but if we zoom out from that and we accept because it's true that essentially

00:51:30.760 | all cells are dependent on mitochondria for their function, why wouldn't we go to this

00:51:35.700 | fundamental layer, uh, first in order to try and improve mental and physical health simultaneously,

00:51:41.380 | right?

00:51:42.320 | It's a very different way of approaching medicine in general.

00:51:44.700 | Normally we go, okay, well, the issue is right here.

00:51:46.960 | That's where the tumor is.

00:51:48.020 | That's where the circuit deficit is.

00:51:49.820 | This is where the, the lesion is, uh, or the growth.

00:51:53.260 | And we're going to go there, right?

00:51:55.180 | But, um, to avoid that, the pathologic state in the first place, uh, these six pillars are

00:52:00.620 | wonderful, by the way, a diet, exercise, sleep, substance, overuse or abuse, stress mitigation

00:52:07.540 | and relationship slash purpose.

00:52:09.620 | Um, so we're going to keep returning to this theme of, of mitochondria is foundational, um,

00:52:16.360 | throughout today's discussion, because I think people need to, to frame their health

00:52:20.440 | in that context.

00:52:21.240 | I really do also, um, years ago, my postdoc advisor, the late Ben Barris, he died, unfortunately

00:52:28.240 | of pancreatic cancer, but just seeing incredible scientists, um, MD and, uh, scientists who really

00:52:34.380 | popularized this, the study of glia prior to that, they were seeing this kind of like back

00:52:38.660 | water science.

00:52:39.400 | No one, everyone thought it was just glue for the brain.

00:52:41.040 | He used to stop us in the hallways late at night and he used to, we called it getting

00:52:45.760 | bend because you'd want to leave.

00:52:47.220 | And he would like, he was a night owl.

00:52:48.660 | It was awful.

00:52:49.240 | And you'd get stuck there, but I'll never forget.

00:52:51.180 | He stopped and he called me Andy.

00:52:52.460 | And he said, he did this numerous times, but he said, Andy, why?

00:52:56.800 | No one calls me that by the way, anymore.

00:52:58.440 | Um, he said, Andy, why is it that as we get older, we have less energy?

00:53:04.300 | And I'm like, I don't know, Ben.

00:53:06.240 | He's like, someone needs to, he's like, why don't you work on that?

00:53:08.340 | Why are you working on these retinal cells?

00:53:10.620 | Like you, you should work on that.

00:53:12.220 | And he said, why is it that we, that our brain is less plastic?

00:53:14.760 | Like, well, I don't know.

00:53:16.020 | I think it's the glia, right?

00:53:17.100 | And there is some evidence that it has something to do with the glia, um, among other things.

00:53:21.880 | But there's a fundamentally interesting question.

00:53:24.340 | You look at kids and they're just full of energy.

00:53:27.300 | And we, there's the NAD hypothesis and there's these other, but it always seems to circle back

00:53:31.900 | to mitochondria.

00:53:32.660 | Yes.

00:53:33.460 | Over and over.

00:53:34.300 | So I think the answer is very clear.

00:53:36.060 | It's, it's, we have a ton of mitochondria early in life and over time it gets depleted.

00:53:41.820 | Is it that simple?

00:53:43.500 | I mean, there are other things too.

00:53:45.320 | There are other things, but I, I actually do think that's a, it's not just the, the number

00:53:51.480 | and density of mitochondria, but it's the health of mitochondria because unfortunately, you know,

00:53:58.120 | our cells have a process for getting rid of defective mitochondria.

00:54:03.380 | Um, it's part of autophagy.

00:54:06.140 | There's a sub kind of category called mitophagy in which defective mitochondria should be shuttled

00:54:14.260 | to lysosomes or shuttled out of cells.

00:54:17.820 | Recent paper actually found that microglia in the brain, again, send out these nanotunnels

00:54:24.900 | to astrocytes and collect defective mitochondria from the neuron and then take care of the disposal

00:54:32.580 | process for that neuron.

00:54:34.140 | We are so cool.

00:54:35.080 | And that when you inhibit that, it appears to increase and accelerate neurodegeneration.

00:54:39.660 | And when you enhance that, it appears to improve, um, or reduce neurodegeneration.

00:54:46.240 | But I think it is.

00:54:47.500 | I think children have more energy because they have healthier metabolism, healthier mitochondrial

00:54:55.720 | function.

00:54:56.320 | And when we look at like, again, like, is there evidence for that?

00:55:02.380 | There's overwhelming evidence for that.

00:55:04.620 | There are thousands of peer reviewed, published articles in leading journals, nature, cell, like

00:55:14.280 | all sorts of journals over the last several decades, just to, again, try to bring this back to just

00:55:20.900 | common sense.

00:55:21.960 | So we have these things called diseases of aging.

00:55:24.980 | What are the diseases of aging?

00:55:27.860 | The diseases of aging are obesity, type two diabetes, cardiovascular disease, cancer, neurodegenerative

00:55:38.220 | disorders.

00:55:38.840 | Those are universally thought of as diseases of aging.

00:55:43.920 | Interestingly, what often gets left off of that category are the mental disorders.

00:55:52.540 | Especially today, a lot of people think of mental disorders as primarily a youth problem.

00:55:59.120 | But in fact, mental disorders, depression, anxiety, psychosis are actually diseases of aging.

00:56:12.440 | So the Center for Disease Control has put out kind of charts of any age group.

00:56:22.920 | What is the probability if you are, you know, a youth in America today that you will be prescribed

00:56:31.680 | an antidepressant, an SSRI antidepressant?

00:56:36.160 | If you're between 20 and 40, what's the probability?

00:56:39.320 | Among the remaining people who are still 20 to 40, among all the people that age, as people

00:56:48.120 | get older, the risk for antidepressant prescription goes up.

00:56:54.100 | The highest category of people prescribed antidepressants are 65 and older.

00:57:00.480 | Really?

00:57:00.760 | Well, I guess in some sense that makes sense, although I would have thought it would be the

00:57:06.740 | younger population.

00:57:07.500 | Most people do.

00:57:08.500 | And that's why I'm saying this, because it's shocking to most people.

00:57:11.740 | It was actually surprising to me, but I was thinking, wait, if my theory is correct, then

00:57:17.140 | mental disorders should be a disease of aging.

00:57:19.260 | And in fact, they are.

00:57:21.500 | Antipsychotic prescriptions, what age group is the most likely to be prescribed an antipsychotic?

00:57:28.860 | Over age 80.

00:57:30.000 | Really?

00:57:31.040 | Oh, it goes through the roof.

00:57:32.420 | Because dementia is associated with 40 to 50% of the people with dementia will have psychotic

00:57:40.780 | symptoms, hallucinations and delusions.

00:57:42.640 | They'll have agitation.

00:57:46.140 | The benzodiazepines, the prescription rate goes up.

00:57:51.560 | Now, with benzos, there is a dip starting at age 65, and that is really because physicians

00:57:59.620 | are explicitly told do not prescribe benzos to people over 65, so the rate starts going

00:58:05.040 | down.

00:58:05.480 | Interesting.

00:58:05.960 | But with antidepressants, it's almost linear.

00:58:08.860 | The older you are, the more likely you are to be receiving a prescription for an antidepressant.

00:58:15.480 | Psychotics, there are some waves and shifts.

00:58:18.480 | Women, for example, around the time of menopause get a peak.

00:58:22.500 | So you get a peak around the age of 20, which is new onset schizophrenia, and then it kind of

00:58:29.040 | comes down a little, and then women, round time menopause, higher peak, and then it kind of

00:58:35.940 | comes down a little, and then late in life goes through the roof, goes through the roof, again,

00:58:42.960 | because of what we call dementia.

00:58:45.020 | So the diseases of aging, anyway, are all of the metabolic disorders and, oh, by the way,

00:58:54.520 | the mental disorders.

00:58:55.880 | And in my mind, we need to tie that together.

00:58:59.380 | That is not a serotonin problem.

00:59:01.820 | Right.

00:59:03.400 | We need to tie that science together.

00:59:05.860 | And the only way to tie that science together is to look at the bigger picture that we call

00:59:12.120 | metabolism.

00:59:12.740 | And ultimately, you have to look at mitochondria and mitochondrial biology to understand it.

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01:01:06.740 | Let's talk about diet and nutrition for a moment.

01:01:09.040 | In recent years, you've talked a lot about the clinical use of the ketogenic diet for various

01:01:16.860 | mental health disorders and cited some spectacular results.

01:01:20.380 | And this has had a huge impact on everybody's thinking about what ketogenic diets originally

01:01:27.380 | were for.

01:01:28.360 | It was developed as a medical treatment for epilepsy, is my understanding.

01:01:31.140 | Only later did it become popular as a potential avenue for losing body fat, et cetera.

01:01:36.780 | But what are some of the ways that people can use diet and nutrition to improve metabolic health

01:01:45.000 | generally?

01:01:45.540 | But let's be more specific.

01:01:47.520 | Mitochondrial health, number, turnover, all the good stuff that happens in mitochondria.

01:01:53.460 | How can nutrition be used to improve that?

01:01:57.080 | Why would it be that the ketogenic diet would improve mitochondrial function?

01:02:00.780 | Or is it that the ketogenic diet bypasses the need for standard cellular metabolism by pulling

01:02:06.900 | on some other cellular metabolism mechanisms?

01:02:11.840 | I'm just trying to draw the link here between a ketogenic diet and mitochondria because you've

01:02:20.260 | well established that mitochondria are central to this whole picture of the mental and physical

01:02:23.800 | health.

01:02:24.700 | I'll throw in a plug before I go deep into the ketogenic diet story.

01:02:30.800 | But you also threw a question in there about other dietary interventions or how can diet

01:02:36.020 | impact.

01:02:36.540 | There is no question diet plays a profound, profound and central role to human metabolism and all of

01:02:46.320 | the consequences of human metabolism.

01:02:48.140 | And you very eloquently laid out the case for early life.

01:02:54.040 | A woman who's breastfeeding her infant, that breast milk has a profound impact on whether that

01:03:03.700 | baby's brain develops normally or not.

01:03:06.760 | that has dire consequences potentially for the outcome and the health of that child.

01:03:15.740 | And it's all about nutrition.

01:03:18.040 | We've known that for decades, that if women are malnourished during pregnancy, it impacts that

01:03:24.780 | infants, the fetus's lifespan.

01:03:29.220 | Really, it increases risk for mental disorders and metabolic disorders, increases risk.

01:03:34.680 | If your mother is starving while she's pregnant or has to fast or has to go without nutrients, it increases that child's risk for metabolic disorders.

01:03:47.460 | Obesity, diabetes, cardiovascular disease.

01:03:49.820 | We've known that.

01:03:51.600 | And that is, you know, there are lots of theories about obesity around that.

01:03:56.320 | It also, surprisingly, increases risk for schizophrenia and bipolar disorder and antisocial personality disorder and all sorts of other mental disorders.

01:04:08.520 | In terms of other dietary patterns, I just want to, and we can do a deep dive into any of these if you want, and then I'll go on to ketogenic diets.

01:04:16.680 | But ultra-processed foods, really bad for your physical health and your mental health.

01:04:21.780 | We have just growing body of evidence for that.

01:04:24.860 | Is that because of the increased calorie consumption?

01:04:27.460 | There's this really nice paper that was published a few years ago showing that people who eat above a certain threshold of processed foods tend to consume, on average, about 500 calories more than they require per day, which might not seem like much, but over time that compounds.

01:04:44.060 | And they gain a lot of adipose tissue, and then the adipose tissue is secreting a lot of things into the bloodstream that make the whole situation even worse, both brain and bodily.

01:04:56.620 | But aside from the caloric load, I mean, is there any evidence that these food dyes and other things that are included in these foods are detrimental to mitochondrial health?

01:05:06.100 | This is a somewhat controversial thing these days because some of these dyes were banned recently, which I saw as a good thing.

01:05:12.740 | But then some of the diehards in the scientific community were like, oh, those dosages represent like 6,000-fold what you'd have to eat, what most people eat, you know, the dosages used in mice.

01:05:23.640 | But the FDA still pulled those dyes, and the FDA is a pretty conservative body.

01:05:29.280 | So I don't know.

01:05:32.700 | Not every chemical is bad, of course.

01:05:35.780 | But are these additives really that bad?

01:05:40.080 | So to try to answer your question, are the chemicals and additives harmful, the real answer is we don't actually have adequate scientific evidence one way or another.

01:05:52.160 | And why don't we have adequate scientific evidence?

01:05:55.420 | Because we're not spending money to research it.

01:05:59.940 | So right now, the rules to this day are that, you know, there's this concept called GRASS, general regarded as safe,

01:06:13.420 | that food companies can develop new molecules that will preserve a food, make a food hyperpalatable, make it tastier, make it more shelf-stable, whatever, whatever they want to claim it does.

01:06:30.680 | They can put these molecules into our food, and they can get away with just saying, well, this is just generally regarded as safe without any adequate safety testing whatsoever.

01:06:48.240 | Now, the new administration, RFK Jr., just recently said he's going to try to change that rule, and I welcome that change.

01:07:00.380 | I think that will be a phenomenal change.

01:07:03.320 | So the reality is that testing hasn't been done on all of these molecules.

01:07:09.540 | There are tens of thousands of molecules, like new chemicals, new additives, things that sometimes aren't even on the label.

01:07:18.060 | That are added to food, and we really don't know for sure for each and every one of them whether this one is safe or not safe.

01:07:27.520 | What we do know overall, and this unfortunately comes down to epidemiological studies, where they just look at hundreds of thousands, if not millions of people,

01:07:39.180 | and they assess, like, how much ultra-processed food is this person eating?

01:07:47.660 | And is that associated?

01:07:49.880 | If we look at large populations of people and we stratify them by these people are eating mostly ultra-processed foods, and these people are hardly eating any, are there differences in their health outcomes?

01:08:06.440 | And the answer to that is unequivocal, and it is perfectly clear.

01:08:12.040 | The more ultra-processed foods you eat, the worse your physical and mental health, both.

01:08:20.180 | It's cardiovascular disease, it's obesity, it's diabetes, it's mortality, it's cancer.

01:08:26.300 | It's also a broad range of mental disorders.

01:08:30.340 | And so we know that.

01:08:34.280 | We've got more granular data that hyper-focuses on the mental health story.

01:08:40.320 | You know, one study, over 300,000 people, the more ultra-processed foods you eat, a direct linear relationship.

01:08:48.680 | It was shocking how linear it was.

01:08:50.720 | The more ultra-processed foods you eat, the worse your mental health.

01:08:55.380 | And it was so striking.

01:08:58.000 | It was not a subtle difference.

01:08:59.620 | It wasn't like, you know, oh, it was a 3% difference between the lowest.