Latest / Gladden Longevity Podcast / The Metabolic Approach to Psychiatry - Episode 357

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The Metabolic Approach to Psychiatry - Episode 357 · Gladden Longevity Podcast

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We had a big issue with our kids about nine years ago where they were diagnosed with
0:04
autoimmune encephalitis, but it presented very psychiatric.
0:08
And then the psychiatric treatments didn't help them,
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in fact made them worse. And that really opened my eyes that you know,
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we have to think about the whole body here.
0:15
Dr. Gladden here. I just finished a conversation with Matt Bernstein,
0:19
who's an MD psychiatrist, and really interesting conversation because
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he was classically trained, you know,
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medications, et cetera.
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And then starting to realize the limitation of that,
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particularly when people are putting on three,
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four, five, six different medicines,
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not doing well, side effects, et cetera.
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And he's kind of transitioned into a different approach.
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And I think you're really going to enjoy hearing about this approach.
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And we go down the rabbit hole on a number of different things related
0:45
to mental health and then how absolutely critical it is to longevity itself.
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It's worth 15 years actually not to be depressed,
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not to have psychosis, things like that.
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But in addition, you're going to hear us talk about some really interesting.
0:58
discussing strategies on how to optimize brain function from his perspective.
1:02
And it interlaces with what we do here at Gladden Longevity.
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So I think you're really going to enjoy this show.
1:07
He went from saving hearts as a cardiologist to rewriting the entire aging playbook.
1:12
Dr. Jeffrey Gladden believes 100 is the new 30,
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and he's got the science to back it up.
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This is the Gladden Longevity Podcast.
1:21
Matt, welcome to the Glide and Longevity Podcast.
1:23
It's good to have you here. Yeah.
1:25
For having me.
1:26
So what's on your heart and mind today?
1:28
What what are you most passionate about that you wanna discuss with us?
1:31
Well, I think my perspective that I'm bringing here is of a psychiatrist.
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I've been practicing for, you know,
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about twenty six years in the field of mental health,
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working with people with all kinds of different conditions,
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but a lot of people with more serious mental health conditions.
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Like what? Rattle some of that off for the audience here.
1:48
What kind of things are you thinking about?
1:50
Sure. Yeah. I mean I've spent a lot of my career working with people with bipolar
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disorder, with and without psychosis,
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schizoaffective disorder, schizophrenia,
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severe major depression, severe O C D,
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PTSD. I also work with people with,
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you know, anxiety disorders, ADHD,
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issues with relationships. I I sort of run the gamut.
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I'm a real generalist. You
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Okay.
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know, but it but I do work with people,
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you know, on the more serious end of the spectrum a lot.
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And ~ we often hit a hit a wall.
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with those folks with the medication approach.
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Meaning, you know, we can we can get people out of an acute episode with some
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of the psychiatric medications.
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But then what happens next is usually not a great scenario.
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Meaning people have metabolic side effects,
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they have neurological side effects.
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Sometimes we don't recognize those as neurological side effects in my field,
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meaning, you know, people are having cognitive problems,
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sedation, lack of motivation, anhedonia.
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Right. So that's a big word. That's a big word for the audience.
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Anhedonia basically means you don't you don't feel pleasure.
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If you're a hedonist, of course you're right,
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you're going after pleasure and anhedonia means that you you can't feel pleasure,
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so life becomes very flat, right?
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Kind of dull. Yeah.
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And sometimes those are from the initial condition,
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but sometimes they're made worse or even caused by the medication interventions
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to try to stabilize people.
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Right.
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And so my big message is that we now have a different way of looking
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at these mental health problems that's based in metabolism that's
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not all about neurotransmitters.
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Not that neurotransmitters aren't important,
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but they've just kind of dominated the way we think about these things completely
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for at least four or five decades.
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And
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We are still hitting these walls.
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And so, you know, Sakai Chis really has needed a fresh look at root cause
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and and mechanism. And I think we have in the last eight or ten years come
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to a place where we have a lot of evidence for us that we have a new
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way of looking at this that will provide a lot of people with benefits that they
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haven't been getting so far.
3:52
It's really refreshing to hear you say that because,
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you know, my background was interventional cardiology.
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My best friend in medical school went into psychiatry actually.
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And ~ I was married to a woman that went into psychiatry and then child psychiatry.
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So I I understand the field. You know,
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I it's it's a funny story, I ~ when I did my psychiatry,
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you know, rotation in medical school,
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I went out and bought a corduroy coat with ~ patches on the sleeves
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and started smoking a pipe. I thought
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Well, I may as well go all in.
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Yeah. I really enjoyed I really enjoyed psychiatry.
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I mean, I I you know, the people on the on the podcast understand that
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I'm very much into the psycho spiritual space and the importance of that
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in terms of meaning of life, purpose and ~ solving big issues like,
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you know, do you feel loved? Do you do you feel safe?
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You know, these kinds of things,
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right? And healing the traumas that we all end up living in reaction
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to that stimulate, you know, anxiety,
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stress, PTSD and
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Things like that, right? So we've gone down the rabbit hole with
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the audience here around those things,
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looking at things outside of traditional psychiatry,
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realizing the limitations of the medic medical approach.
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And you know, it ca it there's there there's a time and a place for everything,
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right? But it's refreshing to hear you say that you're kind of moving outside
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of that. So let's let's talk that through.
5:07
What what direction are you going when you talk about looking more at
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the root cause of things? Yeah.
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Yeah,
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it's really thinking about metabolism and energy production as the main thing that's
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failing in all of these psychiatric conditions.
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So we're talking about mitochondrial function.
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Is that what you're talking about?
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Just not enough ATP in the brain.
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That can certainly be a piece of it.
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It's a big piece of it. Yeah. Yeah.
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Might there's been shown to be mitochondrial dysfunction in post mortem brains
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of all these serious mental illnesses.
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So in and I think the one of the reviews I looked at in schizophrenia and bipolar,
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more than a hundred problematic mitochondrial proteins,
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you know, found. ~ in major depression about fifty or so.
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So ~ mitochondria is a big part of the story.
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It's not the only part of the story.
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I mean, I think we we're sort of working a little bit backwards from
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the mechanisms that we know about these approaches from the work
5:59
in epilepsy over the course of many decades,
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and which one of those are really,
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you know, seem important for psychiatry.
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And turns out most of them are important in psychiatry.
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It's interesting. You're kinda you're kinda as a psychiatrist,
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you're kinda getting pulled back more into the medical side of the sphere than
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the right pure psychiatric side and even actually into the functional medicine side
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of of the world, right? Absolutely.
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Yeah, that's been my evolution in my career.
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I was traditionally trained in psychiatry and we had a big issue with
6:27
our kids about nine years ago where they were diagnosed with autoimmune
6:31
encephalitis, but it presented very psychiatric.
6:34
Psychiatric treatments didn't help them,
6:36
in fact, made them worse. And that really opened my eyes that you know,
6:39
we have to think about the whole body here.
6:41
We have to think about all of these systems,
6:43
the immune system, the endocrine system.
6:46
Metabolism, you know, we can't just isolate the brain from the rest of
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all of that and expect to help most people.
6:53
Yeah, it's r it's really interesting how siloed,
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you know, medicine is in general,
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but psychiatry in particular has become fairly siloed away from,
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you know, does this person have subclinical hypothyroidism?
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You know, do they have enough estrogen in their brain?
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Do they have enough testosterone?
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You know, all these things that that we know and understand are really critical.
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Yeah, I think you're understating that.
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It's it's very, very siloed. It's not somewhat
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No.
7:17
siloed. Yeah. I mean, I think you go to a psychiatrist and they're diagnosing
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you based on the DSM, which is a list,
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a checklist of symptoms. Yep. Made for inner rate of reliability,
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not really designed at all for validity or finding out really what
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the true biological or root cause of these conditions are.
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And then we added that together with a lot of assumptions.
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reverse engineered from some of the medications that
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are effective that neurotransmitters are the root cause and there's really very,
7:47
very little evidence for that.
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They're part of the story, but they're not close to the root of the cause.
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They're downstream. And so we've ended up having a field that can,
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you know, accurately, reliably make a diagnosis based on what someone else would
8:00
make, but we're just putting words to biology and then we're prescribing medications
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based on
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those symptom clusters that are unfortunately,
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you know, not effective for many,
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many people. And then we label them,
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you know, treatment resistant when we can't help them.
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It should be that they're that their ~ clinician is resistant
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to actually understanding what's going on,
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quite honestly. Right. That's right.
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That's right. It's clinician resistant.
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So
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Yeah,
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and you mentioned a few, you know,
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potential, you know, medical causes.
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These are not the kind of things that psychiatrists routinely look into.
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Mm-hmm. You know, we're not we're doing you know,
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if if an outpatient psychiatrist is doing any medical workup at all,
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which you know often is not done.
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Right.
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Exactly.
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But even if they do, it's gonna be pretty cursory.
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And the reality is I'm not trying to say that it's easy to find a root cause on,
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you know, a medical root cause is
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very challenging that requires a lot of testing,
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a lot of expertise. And we're not going to get that much help from
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our medical colleagues. We can send the person back to the primary care doctor
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and say, well, I I think we really need a very thorough organic workup
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of medical causes. And that's not going to happen either.
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So I'm not saying I have an easy solution here,
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but
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But
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we've got problem. It's a great point because if you send them back into
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the into the same system from whence they came,
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they don't really have the tools to to get to the root cause either,
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let alone the root cause of the root cause,
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right? So people that are in that system are kind of stuck in a way.
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It's like they're swimming in a in an ocean that doesn't really have
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the solutions for them. And it can be very frustrating for them and their families.
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I mean, there's tremendous frustration with that.
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So if you're listening to this and you have somebody in your family who's
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caught in that ocean, you know,
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you'll want to listen to what we're going to talk about here.
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So what are some of the things,
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you know, when we think about it,
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we we start with the genetics,
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right? We like to look at what's the genetic predispositions,
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right? For ADD, ADHD, for response to different medications,
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if that's ever required. You know,
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what about depression? What about cognitive decline?
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What about cardiovascular dis we like to look at all that so we get a sense of,
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you know, what's the what's the landscape?
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And then we'll do a lot of functional testing to look at the brain through about
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five or six different lenses to get a feeling for how it's working or not working,
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understanding ~ glucose metabolism,
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insulin levels, cardiovascular f performance,
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you know, on and on. Thyroid's a big one,
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quite honestly. We find a lot of subclinical hypothyroidism
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by doing resting metabolic rates on people that have normal,
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quote unquote, normal thyroid blood tests,
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right? Which is a big one. And then hormone optimization is a big one also,
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particularly for
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For aging people. So I'm curious,
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what kind of things have you discovered and mitochondrial function,
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you know, as we talked about earlier,
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we have many ways to dissect the mitochondria here too.
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So what are you doing and how are you doing it?
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Are you ordering these tests yourself or what's your approach?
10:50
Yeah,
10:50
I'm not I'm not getting quite as thorough of a deep look as you're describing there,
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but I do get a very thorough lab panel looking at metabolism
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and nutritional markers as well as you know,
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thyroid, all the you know, all the potential thyroid tests that I can test for.
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So I'm I'm using a standard lab,
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but getting, you know, a really big panel and workup to see if we
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can find anything there. And then,
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you know, I have, you know, a protocol of intervention because I think,
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you know, people they do want to see if there's any root causes.
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We still often don't find them when we do that kind of testing,
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but we do have a protocol that is very effective at this point for many,
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many people with these various mental health conditions.
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And so that's exciting because it's also a very safe intervention.
11:33
Yeah, no, that is exciting. I would encourage you to look deeper.
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You know, there is ~ other testing out there that quite honestly we find
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to be incredibly useful. Like even knowing someone's genetics around the
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the DIO two SNP, you know, how well people convert T four to T three in the brain.
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When people have a reduction in the ability to do that,
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systemically even they can have a normal resting metabolic rate,
11:55
normal thyroid lab work, and yet still be energy deficient in the brain because
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of that. So pretty pretty fascinating.
12:03
Yeah.
12:03
That's sound interesting. What's the intervention that you give if in that
12:06
Three.
12:06
you just give T three, yeah. Yeah.
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Which interestingly enough, there's a long literature psychiatry of giving
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T three as an adjunctive treatment for depression without any testing of course.
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And and you know, it only works in a subset of people.
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But that's that's really interesting.
12:22
Yeah.
12:23
Yeah, this is the way you can have more precision about who you might think about
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it for. Right. So yeah. Yeah, I'd encourage you to push continue.
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I love the path you're going down.
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I would just encourage you to push deeper into it.
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But even with even with what you're doing,
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explain to us kind of some of the things that you find and some of
12:38
the things you correct, what you've learned and what you're seeing
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is actually helping. Yeah.
12:42
Yeah. So I mean, you know, what I'm seeing is the most helpful intervention
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for people with with psychiatric conditions is the ketogenic diet.
12:50
Okay.
12:50
A well formulated version of the ketogenic diet
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So what does that look like? Describe a well formulated ketogenic diet for us.
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What is what do you think? Sure.
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So first, you know, what what does ketogenic mean?
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It means that you're eating in such a way that you're basically forcing your body
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to use fat as its main source of fuel instead of carbohydrates.
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So we're we're burning fatty acids th in the muscles and throughout most
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of the body, and we're converting some of those fatty acids into ketones because
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long chain fatty acids don't make it into the brain.
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They don't cross the blood-brain barrier.
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Right. And so the the liver will chop up some of them into these smaller
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packets, ketones that do get into the brain.
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And in that kind of metabolism,
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ketogenic metabolism, ketones become an important fuel source in the brain.
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And, you know, that can in and of itself provide some benefit,
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you know, when there's brain insulin resistance in certain regions.
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And there are some regions of the brain that are very highly susceptible
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to insulin resistance, even when there's not insulin resistance measurable
13:48
in the rest of the body. And those regions happen to be very important
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for the mental health condition.
13:53
That's really interesting. Yeah.
13:54
One of the things we do is we do two hour glucose tolerance tests with insulin
13:58
curves on everybody. And we're stunned that many people show insulin resistance that
14:03
with a normal hemoglobin A1C and a normal fasting blood sugar.
14:06
Because when you stress the system,
14:08
you know, put the pancreas on a treadmill,
14:10
so to speak, you'll see that they're running high insulin levels.
14:13
They have a very exaggerated insulin release in response to the
14:16
to the seventy-five grams of glucose.
14:18
And they may even actually control the blood sugar.
14:21
So you wouldn't pick it up on a continuous glucose monitor,
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but they're dumping tons of insulin into the system,
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which of course has a lot of aging properties.
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And then in some cases, they don't control it very well.
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So it's interesting that, you know,
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we've learned that too much glucose in the brain causes a
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lot of neuroinflammation also,
14:38
it seems like. And the ketones tend to tend to calm down neuroinflammation.
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So they do.
14:44
They do, yeah. One of one of the,
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you know, mechanisms by which ketogenic diets help in epilepsy,
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we know for sure, and most likely also one of the mechanisms why they help
14:52
in in mental health too. Mm-hmm.
14:54
So so those areas of the brain that are sensitive to insulin resistance happen
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to be very important for psych psychiatric conditions.
15:02
What are those areas of
15:03
So it's the it's the hypothalamus,
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mm-hmm, the hippocampus, and the amygd and the amygdala.
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So,
15:09
Okay.
15:10
you know, very crucial.
15:12
Regions for the things that people come to see me.
15:16
Right. So then that's also going to be related to hormonal control,
15:18
right? So the hippocampus. The hypothalamus is going to be
15:22
or the hypothalamus rather. The hippocampus is going to be associated with memory
15:25
and then the amygdala is going to be associated with stress responses
15:28
and things like that. Yeah.
15:30
fear center
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in our brain. That's right. And so if those are running out of energy,
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which they will, if that those areas become insulin resistant,
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they're gonna dis you know be dysfunctional.
15:40
And then the ketones come in and they don't require an insulin signal
15:43
to diffuse into those regions,
15:45
into those into those areas. And so we rescue that energy problem almost immediately
15:50
with ketones in that scenario.
15:52
So that's one of the you know purported scenarios that we're you know thinking about
15:56
in terms of why this works so well for people.
15:59
So let's say let's say you you use a ketogenic diet,
16:03
you're avoiding carbs, you're avoiding things that have a high glycemic index
16:08
and high glycemic load, right?
16:09
Well, understand glycemic index is basically how rapidly does your blood sugar rise
16:13
in response to it, and glycemic load is how much sugar is in the thing altogether.
16:17
So you're kind of minimizing those foods.
16:19
And if you're listening to this,
16:20
you can look that up. Foods that have a high glycemic index and foods that have
16:24
a high glycemic load, those would be the ones to avoid.
16:27
But once you do that, then what what do you actually notice from a s let's call
16:31
it a symptom improvement? What what are you seeing?
16:34
Let's let's just walk through some of the common disorders like anxiety,
16:37
depression, PTSD, things like that.
16:39
What do you what do you actually see?
16:41
So yeah, if someone's doing that intervention,
16:44
that diet, you know, first thing we see is they get into ketosis.
16:46
We're measuring ketone levels.
16:48
And, you know, in the program where I am,
16:50
you know, we can often get people into ketosis in a few days.
16:53
Without patients, I don't generally have it go so quickly because it's
16:56
a big change in your physiology.
16:58
it's better to do it slowly if you can,
17:01
if you're at home. So that's the initial phase is get into ketosis.
17:05
Then there's an adaptation period.
17:06
Sometimes as soon as someone gets into ketosis,
17:09
they do
17:10
notice benefits. And that's really,
17:12
you know, harking on that mechanism we just talked about.
17:14
That, you know, energy rescue mechanism could be fairly quick.
17:18
Some of the other mechanisms that we think about can take longer.
17:21
And so for some people it could be a number of weeks of after adapting
17:25
to ketosis before they start feeling benefits.
17:27
You know, these other mechanisms which we can get into.
17:30
But pretty universally we do see people improve their energy,
17:33
their vitality, lowering of anxiety,
17:36
improvement in mood.
17:38
Memory improvement, cognitive improvements.
17:41
I would say more cognitive flexibility is very common too.
17:44
And cognitive flexibility is a hallmark of mental health,
17:49
in my view. If you can more flexibly think about a situation,
17:53
you have got an ability to to manage it.
17:55
Yeah. So what you're saying is that somebody that's depressed or anxious,
17:59
they kind of get caught in a thought loop,
18:01
right? Where it's hard for them to get out of that.
18:03
They're har it's hard for them to have a different perspective on the situation.
18:07
That's right.
18:07
And so by cognitive flexibility,
18:09
you're saying that people can then sort of stand outside that loop and look
18:13
at it from another vantage point,
18:14
right? Exactly.
18:16
Exactly. And it makes a huge difference in terms of being able to people being able
18:20
to use the advice they're getting from friends or family or from
18:23
a therapist to actually improve what's going on in their life.
18:26
People can get all kinds of incredible advice and not be able to
18:30
do anything with it. That's right.
18:31
Not be able to hear it really,
18:32
right? Right. 'Cause
18:34
they're stuck in a loop. Yeah.
18:36
Yeah, that's interesting. And so in those situations,
18:39
are you taking them off their meds or you're never starting meds?
18:43
Or how how's that working with your,
18:46
you know, your
18:46
~ Excellent question. The medication piece is a very important part of,
18:50
you know, I think doing this well,
18:52
you know, doing it with success.
18:54
People generally come to me, they're often on multiple medications already,
18:58
multiple psych psychotropic medications.
19:00
It's very common. You know, we talked about the scenario where people
19:03
get into a situation, they're starting a medication,
19:05
they're getting a little bit of a response.
19:07
Typically then the next step is,
19:09
well, let's add another medication.
19:10
They're not taking away the first one,
19:12
they're just adding another one.
19:13
Right.
19:14
And then people end up on, you know,
19:15
with some of these conditions,
19:16
it's you know, like bipolar disorder,
19:19
for example. It's very common for people to be on three to six medications just
19:24
for their bipolar disorder.
19:25
mean when you stand outside the system and look at that,
19:27
it seems like there's gotta be a better way,
19:30
right? Right.
19:31
Yeah, and so sometimes we don't see the full benefits until
19:35
we start lowering medication. That's also
19:38
Okay.
19:39
a very tricky scenario as well,
19:41
because all of these psychotropic medications have potential withdrawal syndromes.
19:46
Right. And that's also not been well enough recognized by the field.
19:50
too. Yeah. I mean the SSRIs are kind of a cla classic case in point,
19:55
right? ~ you stop them too quickly and you lose serotonin signaling and then,
19:59
you know, you can exacerbate depression or anxiety or whatever else,
20:03
right? So yeah, it's tricky. It's very tricky.
20:05
So if you're listening to this,
20:07
the point is I wouldn't just start a ketogenic diet and quit all your medicines next
20:11
week. That's probably not the right that's probably not the right that's probably
20:14
not the right answer. However,
20:16
I think you can have the aspiration
20:18
to wean down your medications ~ over time under some supervision to make sure that
20:24
you're doing it properly. But what are you seeing from the standpoint
20:27
of medication reduction in the people that you're treating through this paradigm?
20:32
Are you able to get them off their meds or you're still there's still
20:35
a couple things that are left?
20:36
Or how do you how are how's that playing out?
20:38
Yeah, no I mean, not everyone gets completely off,
20:41
especially as I said, people come in with these more serious conditions like bipolar
20:45
with psychosis and schizophrenia.
20:47
But we can often reduce the medication burden by an enormous percentage.
20:50
You know, sometimes fifty percent,
20:53
seventy five percent, even seen it,
20:55
you know, ninety percent. And there's some people who have been able
20:57
to get completely off their medication.
20:59
So
21:01
And there's some people who just stay on their same medication because they feel
21:04
good on it and they're feel safe on it and they want to stay on it.
21:06
And they're doing well with the combination of the metabolic approach with their
21:09
medication. So it's not one size fits all.
21:12
But I think it is very important to recognize that for some people,
21:15
they're not responding. And part of that may be that they're on medications that
21:21
are really impairing their metabolism as well.
21:23
And, you know, many of the psychotropics fit that category.
21:26
Yeah, so tell us about the impact of the psychotropics on metabolism.
21:30
Are they poisoning the mitochondria in some way?
21:32
Are they increasing insulin resistance?
21:35
Or tell us a little bit about the
21:36
I wish I could tell you the exact mechanisms.
21:38
I don't think that's been studied enough to really know.
21:41
What we do know in big studies is that many of the what that we
21:46
now call atypical antipsychotics or second generation antipsychotics are very,
21:50
very harmful for metabolic health.
21:52
You know, with weight gain, insulin resistance,
21:55
dyslipidemia, full metabolic syndrome ~ being very common.
21:59
And it's also true of, you know,
22:01
some of the ones that are considered safer still have a metabolic signal,
22:04
but they're better than the, you know,
22:06
some of the other ones. But even SSRIs and,
22:09
you know, what they call mood stabilizing medications also have
22:12
a negative metabolic signal, just not quite as severe as some
22:16
of these atypical antipsychotics.
22:18
Yeah, you hear a lot about people gaining weight when they get
22:20
on antidepressants or antipsychotics or that kind of thing,
22:24
right? It's very, very common for people to quote unquote gain weight.
22:27
And, you know, in in our society,
22:30
you know, with all the GLP one craze,
22:32
people are trying to go the other direction.
22:33
So and and have been for a long time.
22:36
Yeah. So that's interesting. So let's talk about another adjunct to this,
22:40
which is exercise. Yeah. I think that's really been under stressed in
22:45
Psychiatric health, quite honestly.
22:47
So tell us a little bit about your insights around exercise.
22:52
So just I mean, just a little detour on talking about some data.
22:55
There's tremendous data on exercise and mental health.
22:58
You know, the meta-analyses have you know more than a thousand studies
23:02
in them sometimes. So, I mean,
23:03
this has been studied a lot. We can we can be pretty certain about what we're saying
23:07
here. And so for exercise for depression,
23:09
for example, has a greater effect size,
23:12
you know, and we measure that often in these studies by a Cohen's D,
23:15
you know, statistic. It's usually in the point six to point eight range
23:18
in for exercise for depression.
23:20
So what does that what does that mean,
23:22
point six to point eight for the audience?
23:24
What does that mean? Okay.
23:25
To a moderate effect size.
23:28
Small effect size is you know 0.2 to 0.5.
23:31
And actually, that's where modern antidepressants come in for depression
23:34
in the 0.35 range. So exercise is significantly more effective than
23:40
antidepressants. The challenge is it has to be intense exercise.
23:44
And it's very, very hard to get someone who's very depressed to do intense exercise.
23:49
Yeah, that's that's the trick right there,
23:51
right? When someone's depressed,
23:52
they're not motivated, trying to get them to exercise is difficult.
23:56
And I should just back up a quick second when I gave the statistics.
23:59
That's for moderate depression.
24:01
That's not for what we consider severe severe depression.
24:04
Sure. I would think prophylactically,
24:06
however, exercise for people that have a tendency towards depression,
24:10
prophylactic intense exercise would be a great way to avoid it,
24:13
right? Going forward.
24:14
Absolutely.
24:14
And especially when someone recovers from a depression,
24:17
one of the things that I would highly recommend is now's the time to
24:21
get into your regular exercise routine.
24:23
Exactly. That's going to prevent the next time you might get depressed.
24:27
Because we now know you're you're prone to it.
24:29
And we there is very good data to show that once someone's had
24:32
one major depressive episode in their lifetime,
24:34
50%
24:34
That's right.
24:35
chance of having a second one.
24:37
And once you've had two, there's like more than a 75% chance of having a third.
24:41
Once you've had three, you know.
24:43
It's most very likely it's going to keep happening unless you take some significant
24:47
action. And exercise is absolutely one of the best things that you could do.
24:51
Yeah, we'll we'll talk about exercise a little bit more because that's very
24:54
interesting. I will tell you I will share that I've got some genetics that
24:57
predisposed me to depression. And I've I've struggled with depression
25:00
at various points in my life. In fact,
25:02
it was at one point I when I started to really feel good again,
25:06
I didn't realize that I'd actually been depressed for the last eight years,
25:08
right? ~ kind of thing. Right.
25:11
And so in in unraveling the knot for myself,
25:15
I discovered that.
25:16
a supplement. Well, I don't methylate well.
25:18
I don't make n neurotransmitters well.
25:20
I don't make enough serotonin and dopamine.
25:22
The receptors may not work quite optimally genetically,
25:25
right? So I'm okay, so now I understand why.
25:28
And then I I got on the right combination of B vitamins,
25:31
right, to support methylation and I needed folinic acid,
25:34
not just methylfolate and things like that.
25:36
So there's some subtleties there that you pick up in the genetics.
25:39
But then also ~ SAMI, which is a methyl donor,
25:42
actually has been
25:44
Kind of a godsend for me, quite honestly.
25:46
And I know it shouldn't be used in bipolar.
25:48
So if you're listening to this and you have bipolar,
25:50
don't run out and start taking SAME.
25:52
But but for me, if I start to feel depressed,
25:55
I can take, you know, four hundred or six hundred milligrams of that
26:00
and literally in ten minutes I feel better.
26:03
because it's it's actually augmenting ~ both serotonin and dopamine production.
26:08
And for me, it's it's like I said,
26:10
I carry it around my backpack because you know,
26:13
if I start to feel something, I'll take it.
26:15
I don't take it every day, but I'll take it and ~ it just turns the corner
26:20
for me super quickly. Yeah. So and I exercise all the time.
26:24
So anyway, I'll just throw that out as a caveat.
26:26
That being said, to return back to exercise.
26:29
There is some really interesting data on the brain and intense exercise.
26:34
And I was reading something recently about the need to actually get to
26:38
a point in the intensity where you're you're developing lactate production
26:42
in the muscle, right? And do you want to talk a little bit about that?
26:45
Yeah, that literature is really interesting.
26:47
You know, lactate does go to the brain and it seems to be a very important signaling
26:52
molecule in the brain, as well as just,
26:54
you know, gets used as fuel as well.
26:56
So that does seem to be one of the major mechanisms by which exercise helps brain
27:02
health is through that lactate mechanism.
27:04
Obviously through other mechanisms too,
27:05
which we could talk.
27:07
Yeah. So if you're if you're listening to this and you're thinking,
27:10
well, I'm gonna start an exercise program,
27:12
I'll start walking through the neighborhood,
27:14
that's better than sitting on the couch.
27:16
And there are some definite health and longevity benefits to that.
27:19
That's it's ~ ten thousand times better than sitting on the couch.
27:23
But to actually get lactate production,
27:25
you've gotta be exercising at a level where your muscles are starting
27:29
to feel that burn, right? Which is related to the acidity that's developing.
27:33
And one of the things that we found is that the best and easiest way to
27:37
do that is with blood flow restriction.
27:39
So if you put on ~ something like B strong bands or katsu bands,
27:44
which is basically kind of like it's not a tourniquet,
27:46
but you put it on and kind of inflate it to where it's like a blood pressure cuff
27:50
on your legs and your and your upper arms and around your thighs,
27:54
and then you exercise, you can develop that lactate production at a lower level
27:59
of activity than you would if you were
28:01
trying to run up and down stairs for 10 minutes to try to get that burnt,
28:05
right? Right. And so that that's a really nice hack is to
28:09
use blood flow restriction. There's another machine called a VASPR that uses blood
28:14
flow restriction. It's on a new step,
28:15
so you're seated and you're going back and forth and it's cool and all that.
28:18
And I did it this morning actually.
28:20
I have one here and one at one at home and one in the office and one
28:24
in California where I have a place also because I like it so much.
28:27
But this idea of blood flow restriction for lactate production,
28:31
if you're listening to this and it's like I'm exercising but I don't feel that much
28:34
better, even when I go for a run,
28:36
think about adding in some some blood flow restriction exercise.
28:40
Yeah. And and sometimes, you know,
28:42
yeah, you have to keep ratcheting up the intensity.
28:44
I think we all get conditioned to,
28:47
you know, this is my workout and it's a good workout for me.
28:50
And I'm just gonna keep doing that workout.
28:52
And it was a good workout for you three months ago.
28:54
But if you keep doing it regularly for three months,
28:57
that's a that's a great success.
28:58
But to keep having success, you need to actually ratchet up your intensity.
29:02
That's
29:03
right. So your body adapts exercise.
29:05
It gets stronger, right? And so that's what you want.
29:07
But to your point, you've got to you've got to switch it up,
29:10
change it up. So yeah, I think I think this is really,
29:13
really important insight. I think it's also true for cognitive function,
29:17
almost anything related to the brain,
29:19
that if you get to that point where you're developing lactate production,
29:23
that it's going to be healthful for your brain.
29:26
And of course we're also improving mitochondrial health,
29:28
you know, right activate PGC one alpha through exercise,
29:32
also through ketogenic diets as well.
29:35
So that's an area where they're synergistic.
29:37
So tell us about PG C one alpha.
29:39
What does that actually do?
29:41
So
29:41
this is a signaling system. It's telling our cells to make more mitochondria
29:46
and to recycle the old damaged mitochondria into parts and build them back
29:52
in the new, high functioning ones.
29:53
you know,
29:54
That's right.
29:55
mitochondria are huge part of this story.
29:57
We've mentioned them before already,
29:59
but you know, in terms of energy production,
30:01
but they do way more than just energy production and I think
30:04
We're now appreciating how important mitochondria are for for mental health,
30:08
way even you know, outside of the energy story,
30:11
which is huge, is all
30:12
Ready.
30:12
Yeah, they're a massive part of the whole aging process.
30:15
You know, mitochondrial dysfunction is one of the twelve hallmarks of aging.
30:19
And so being able to boost them and rejuvenate them.
30:22
Another substance is urolithin A can be very,
30:26
very important for something called mitophagy,
30:29
which is the ability to actually clear out old mitochondria and replenish them with
30:33
youthful mitochondria. And it works along with PGC one alpha.
30:36
And then, you know, you've heard about things like methylene blue that actually will
30:39
increase ATP production across the electron transport chain.
30:43
It can fill in at any point. And then,
30:45
you know, co q ten and NAD and all the things you've heard about that support
30:49
as well as B vitamins and getting toxins out like lead and mercury and
30:52
~ things like that, all those things support mitochondrial function.
30:56
So yeah.
30:57
Yeah, so yeah, you we you know we now know that mitochondria are I mean they respond
31:01
to all those things. The other,
31:02
you know, thing to bring it back to is that you know,
31:05
mitochondria respond to our stress state as well.
31:08
There's now lots of very good evidence for that,
31:10
too.
31:11
Yeah, tell us about that.
31:12
Yeah, so yeah, there there's a few labs,
31:15
in particular, Martin Picard at Columbia is publishing a lot about this,
31:19
you know, actually looking at you know what the mitochondria
31:22
are doing under microscope.
31:23
They they have studies where they actually look at people's stress states
31:26
and see how the mitochondria respond in these various stress states.
31:30
And and they do respond and they respond to mind body practices as well to you know,
31:36
to reduce stress. And so, you know,
31:38
we think the mitochondria are you know,
31:40
they're
31:41
A very important function in terms of producing energy,
31:43
but we have to think about all these other functions that they do as well.
31:46
And so they huddle around at the end of neurotransmitters
31:48
to get neurotransmitters to release.
31:50
They're involved in the initiation and resolution of inflammation.
31:53
They can actually initiate apoptosis or cell death when needed.
31:57
They're involved in transcription of genes in the nucleus of the cell.
32:01
So I mean, they're almost like,
32:03
you know, little CEOs of the cell,
32:04
in addition to being energy factor.
32:07
That's right. Yeah, they can help repair DNA,
32:09
making ~ purines and things like that.
32:12
They do they they're amazing. They're also sentinels for the cell.
32:15
If a infection comes along or something like that,
32:17
they're the first to recognize that and signal the cell about it.
32:20
So there are many, many functions to these mitochondria.
32:23
You know, one of things that we really stress here is,
32:25
you know, our target for longevity is when we're age a hundred is to have
32:29
a thirty year old body but develop a three hundred year old mind,
32:32
right? Right.
32:33
With all the perspective, right?
32:34
Tranquility, sense of transcendence,
32:37
become unencumbered by healing,
32:38
all the traumas we live in reaction to,
32:40
understanding how loved we are,
32:42
how safe we are, all of that's based on a psycho spiritual area.
32:45
And then here we can actually measure the status of someone's nervous system.
32:49
We can actually see how stressed they are.
32:51
Using something called brain tap,
32:53
neurocheck, put a couple clips on their wrist for about five minutes,
32:56
and it looks it looks deep into the to the nervous system,
32:59
also.
33:00
The algorithm will imply how much stress the adrenal glands are under because stress
33:04
is not only neurological, it's hormonal as well.
33:06
And it's really interesting because we can teach people how to meditate.
33:11
We can put them into theta states or alpha states,
33:15
which are states of slow brain waves that correlate with with meditation.
33:20
And we can actually see significant improvement in their stress scores.
33:23
~ if they'll do that, you know,
33:25
twice a day for a a couple of months.
33:27
Let's say we don't see them in two weeks,
33:29
but
33:30
We see them back in a couple of months and retest them,
33:32
we'll see really significant improvement.
33:34
So to your point about mindfulness being at the center here o as well
33:39
of not only mitochondrial function but mental health in a way.
33:43
~ that's a really nice intersection.
33:45
Yeah.
33:46
Absolutely. Yeah. And and I've seen that many times actually where
33:49
we are optimizing in our protocol,
33:52
you know, their diet, they're making ketones,
33:55
their insulin is very low, they're exercising.
33:58
We we get out walking in the sun and multiple times a day getting
34:02
s enough natural sunlight and they're sleeping well.
34:04
But if they're still stressed,
34:06
they're not feeling well yet.
34:08
That's right. That's right. No,
34:10
it's it's a really big deal. And stress,
34:12
I think, you know, getting in the right brainwave state is a big help.
34:15
But I think there are also this is where psychological spiritual insight
34:19
to be able to resolve those traumas and to feel ultimately feel safe,
34:23
to feel lovable, to feel acceptable,
34:25
you know, all the things that that people go through life dancing around,
34:29
so to speak, right? getting rid of shame and guilt and other things that encumber
34:34
us, right? This is a big this is why talk therapy is helpful.
34:37
Yeah.
34:37
You sure you didn't want to go into psychiatry?
34:39
I mean you you're
34:40
I love
34:40
psychiatry. I that's why I bought the that's why I bought the jacket,
34:43
you know. So but you know, it brings us to the point of a lot of these things
34:48
are imprinted into the nervous system through experiences.
34:51
And talk therapy can only take us so far because it's not an experience,
34:56
it's an insight. And so I don't know if you want to go in down the path here,
34:59
but ~ there's a lot of work being done with psychedelic ~ assisted therapies,
35:04
either ketamine, psilocybin, ibigaine,
35:07
things like that that are showing some dramatic
35:09
dramatic impacts on people like people that we have a guy in our clinic
35:13
who was an alcoholic, did ibogaine like almost two years ago now,
35:18
hasn't had a drink since, right?
35:19
Things like that, which would never happen with,
35:22
you know, anything else, quite honestly.
35:24
And many people with psilocybin experiences or buffo experiences that
35:28
get new insights into the nature of reality and why they're here
35:33
and things like that are very meaningful.
35:34
And all of a sudden it's like,
35:35
okay, I get it now.
35:37
So I don't know if you want to speak to that,
35:38
but that that can be a very powerful tool.
35:40
It can be. Yeah, I'm happy to talk about it a little bit.
35:42
I mean, I think first we do need to put some caveats on
35:45
a discussion about psychedelics because I've also been talking about people with
35:48
serious mental health conditions.
35:50
Yes, that's right.
35:51
So it's just important to say that,
35:53
you know, if someone has one of these more serious conditions,
35:56
it may be very dangerous to take one of these psychedelic medications.
36:00
That's right.
36:01
so that's important. So, you know,
36:02
psychedelics, I think we're talking about a different kind of population,
36:05
someone who, you know, has pretty good mental health.
36:08
Potentially. They have some strengths.
36:10
They're not anywhere near a psychotic state.
36:13
They haven't had a psychotic state before.
36:15
But they're really maybe struggling through,
36:17
as you said, their their psychosocial,
36:19
spiritual identity. You know, they've had traumas.
36:22
They're having trouble really figuring out what their meaning
36:24
and purposes and connections are in life,
36:27
struggling with their relationships.
36:29
So in that kind of setting, you know,
36:31
then these can be very helpful.
36:33
And and so and there's a little bit of a division too,
36:35
ketamine being not a classic psychedelic.
36:38
Probably quite a bit safer too,
36:40
in terms of from a psychiatric perspective at least.
36:42
Yep. Because it's not really inducing that,
36:45
you know, full long psychedelic experience like some of these other compounds.
36:49
And so, you know, we we do have some literature now on ketamine being very helpful
36:53
for depression. That the medication itself can be helpful for depression.
36:57
It also induces some neuroplasticity,
36:59
which can be really helpful when someone's in a in a healing process,
37:02
a therapy process and trying to change their life.
37:05
These more classic psychedelics,
37:06
which are not
37:07
legal to use so far in the United States ~ therapeutically,
37:11
although they may that may change very soon,
37:13
are riskier for people. You know,
37:15
just to to put that out there,
37:17
you know, I know some people who have done Ibogaine in therapeutic settings
37:21
in other countries who have had really negative outcomes too.
37:24
So I just want to put that out there that
37:26
That's right.
37:26
it's a very, very, very powerful substance.
37:29
And it will take people to places that they had no idea existed.
37:34
That's right.
37:35
As you said, sometimes people can come out of that.
37:37
stronger than they've ever been before and ~ healed in in a way
37:41
and other people they they may not have such a such a pleasant experience
37:45
and it may actually lead to some harm.
37:47
So
37:48
I think it's a great point. I think it's a great point.
37:50
It's kind of like you've got to be healthy enough to do the exercise,
37:54
right? if you're not if otherwise you can hurt yourself,
37:57
right? If you're still if you're still trying to run on a broken leg,
38:00
that's not a good idea. Right.
38:02
And so that's kind of the analogy.
38:03
But I think if people do get to a point where they are healthy enough,
38:07
then you know, with evaluation,
38:09
with talking to somebody that's skilled in these kinds of things,
38:12
we've seen it actually be transformative for a number of people,
38:15
you know, when they're when they're the right person.
38:17
Right. Absolutely.
38:19
Yeah, yeah. I think it can be the absolute right thing for certain people
38:22
at at a certain time in their life or at various points in their life.
38:26
And you know, it harkens back to,
38:27
you know, there is really I mean,
38:29
I'm sure you know this very well,
38:30
there's you know, really strong literature for longevity,
38:33
for things like social connectedness and having meaning and purpose.
38:37
These these are really durable concepts.
38:40
And so someone could again could be doing everything right with all their protocols.
38:44
They figured out their genetics,
38:45
they've got it all going.
38:47
They even may have a good job and great relationships or you know on the surface,
38:51
but something feels empty or missing.
38:55
They don't really feel connected to their life.
38:57
They don't really feel as much meaning as purpose as as they should or
39:02
or or feel like would
39:03
Would like to. Yeah.
39:04
like to. You know, that's a that's a interesting thing to be going after
39:09
and a really powerful thing to go after in those situations.
39:12
And and it does require, I think,
39:14
you know, expert guidance, you know.
39:16
It
39:16
does. Yeah, totally.
39:17
really need
39:18
to trust the people who are who are guiding you through that kind of process.
39:21
That's
39:22
right. Yeah, that's right. It's not for everybody,
39:24
but for the right indication, I think it can be ~ quite profound.
39:28
You know, to your point, there's some really nice research now coming out of Baylor.
39:32
I was talking with a woman that does the research down there
39:34
and they're showing nice longevity benefits,
39:36
telomeres are being lengthened and you know,
39:38
brain gray matter is increasing in size and you know,
39:42
neuroplasticity is increasing and you know
39:45
Many, many things, skin and fur on the on these animals is improving.
39:49
You know, they look younger, they act younger.
39:50
So it's a really interesting that these plants,
39:54
you know, have some utility ~ and again in the right setting,
39:57
in the right context for the right person.
40:00
But it's kind of exciting to see that kind of open up.
40:03
And and and and fungi, of course,
40:05
when you talk about Simon. Yeah.
40:07
Sure. Well yeah, the mushrooms,
40:10
of course. Yeah. Well Matt, it's been a a pleasure chatting with you about all this.
40:14
Is there anything else that you wanna let the audience know about or
40:17
Well, I mean, just thinking about longevity a little bit,
40:20
you know, in in my area, I'm talking about these folks with more serious illness.
40:23
And just want to put it out there that,
40:26
you know, people with those serious illnesses have on average
40:30
a lifespan that's fifteen years shorter than the average population.
40:35
That's right.
40:36
I mean, if we think about, you know,
40:37
trying to optimize longevity, you know,
40:39
w we can do a lot of things and,
40:41
you know, as you said, you may get to really incredible places.
40:45
But we've got really low hanging fruit here.
40:47
We've got people who are not even making it to,
40:49
you know, the average, you know,
40:51
by an order of fifteen years and having,
40:53
you know, terrible health span consequences along the way.
40:56
And so I just wanted to get that that point out there.
40:59
I think it's a really important one for people to hear.
41:01
Yeah, in our world, you know, we really have five circles that need
41:04
to be addressed to optimize this target of a hundred ~ at age a hundred
41:09
to have a thirty year old body and a three hundred year old mind.
41:11
And the first circle, the one that encircles all the other ones,
41:14
is life energy, which is a psychospiritual space,
41:16
because we know that how critical that is.
41:18
And then inside of that is longevity itself,
41:21
which are related to the hallmarks of aging,
41:23
health, of course, performance,
41:25
right, which is
41:26
Being fast, agile, strong, quick,
41:27
balanced, learning how to go in a flow state.
41:29
And then the environments we reside in,
41:31
architecting those to support the mission.
41:33
But the circle that encompasses all of that is the psycho spiritual space.
41:38
And maybe that harkens back to why I enjoyed my psychiatry rotation,
41:41
right? But and ~ some spiritual things that I did when I went to seminary
41:45
for a brief period of time. But the point is this is this is critical.
41:49
That's fifteen years. I mean, you know,
41:51
think of any intervention that's gonna add fifteen years.
41:53
I mean
41:54
There aren't that many that we know of that's gonna add fifteen years.
41:57
And there it is right in front of us,
41:59
right? So yeah. Well again, really a pleasure.
42:01
I appreciate you taking the time to chat with us.
42:03
I think I think the audience learned quite a bit here.
42:05
So that was very fun. Yeah.
42:07
Thanks, yeah, I appreciate it coming and thanks for inviting me.
42:10
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42:12
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42:14
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42:19
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42:27
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