Jamie Martin
Welcome to Life Time Talks in our series on performance and longevity with MIORA. I’m Jamie Martin. I’m here with Jim LaValle the chief science officer at Life Time. He’s also a longtime clinical pharmacist, the co chair of the American Academy of Anti Aging Medicine, and the Chair of the International Peptide Society. Hey Jim, how’s it going?

Jim LaValle
Going great, my brain is percolating.

Jamie Martin
We’re ready. Well, you just let us right into our topic. We are talking about brain health. There is a lot of emerging science that’s really fundamentally changing the way that we think about cognitive health with innovations in testing and our understanding of what it takes to take proactive care of our brain.

So we’re diving into this as it relates to performance, aging, and all of those pieces. So just set the groundwork for us. Why is brain health such a major focus in the long space of longevity?

Jim LaValle
Well, I mean, right now, if you live long here, say in in particular in the US, you got a greater chance of Alzheimer’s and dementia. And if you’ve lived with a family member that’s had dementia or has had Alzheimer’s, it’s scary. Yeah. It’s very scary. And I think people are very aware that you know, they want to have their cognitive processes about them. They wanna be able to focus. They want to be able to enjoy their life.

And your brain’s at the center of it. Not just for the thing of you know, focusing consciousness. And hey, look, I remember what I’m saying. And you know, do I remember where my keys are? Right. Yep. It’s you gotta remember it’s the commander in general of your whole body, your nervous system down. I mean, all the signals kind of somewhat start there or it takes in information from other parts of the body in order to change what needs to happen, right?

And so the I mean, the w we could not do justice on discussing the brain probably in twenty episodes, right? I mean, you know, you look at all the different aspects of what we should be looking at, but we’re gonna give it a shot for the next hour.

Jamie Martin
We’re gonna try our we’re gonna do our best. I mean, I think when we think about brain health and and as it relates to aging, there’s often been this kind of mis it’s a misconception that the brain is eventually gonna decline or there’s like losing some of our brain function, the cognitive awareness is going to decline with age. But in many ways there are things that are preventable or even reversible when it comes to cognitive health with the right interventions, right?

Jim LaValle
Correct. Yeah. And you don’t necessarily have to lose it. So you think of the, you know, remember that that that category or of it was a study on nuns that were doing like crossword puzzles and all that kind of stuff later into their life and they were still incredibly sharp. I think you have to exercise your brain. Right.

So, you know, the you know, whether you’re doing a crossword puzzle or you’re doing Sudoku or you have your I I mean, I’m gonna tell you right now, I’m guilty of it because I do exercise my brain. I’ll play games on my phone because I like feeling like I’m, you know, do an IQ game or try to, you know, try to really solve problems. So I think that’s important. So first is exercise your brain. Right. as you’re aging.

And then there’s the big things, you know, eating, you know, the whole process of eating better, but we’re going to define that as to what diets are going to be good and which ones aren’t. Right. What starts becoming the problems. Because there’s a lot that goes into keeping a healthy cognitive capacity and the ability of the brain to maintain being commander in general.

Jamie Martin
Yes. So before we get to that, ’cause we’re gonna go into some of those like the foundational things for good brain health, like we do with all of the topics we cover. Let’s talk about where the science is going, like like testing.

I know when we were prepping for this episode, you were kind of sharing, like, hey, there’s these really interesting tests that are coming out that are showing promise for being able to kind of gauge where you are from a cognitive health standpoint. You know, what are the emerging biomarkers, blood tests, or imaging tools that might be able to give us a realistic picture of what our brain health is like?

Jim LaValle
Yeah. So I started doing that at my institute in in Ohio where we imaged ten fifty-five to seventy year old males and females. We cross matched them. They had, you know, minimal cognitive loss, but at the same time we could measure it. Yep.

And what we did was we did what was called a like a functional MRI where we d we used something called a diazepam tracer and that made us look at their acetylcholine. Think of that as your molecule of memory kind of. It’s what it’s the RAM. It keeps the brain from overheating basically, right? Okay. Versus glutamate, which is very excitatory. Right.

And then what we did was we had people take phospholipids because phosphatidylcholine, phosphatidylethanolamine, phospholipids end up building acetylcholine in your brain. Right. And so we gave them phospholipids. They were put on a multivitamin. We did not instruct them on diet or exercise because I didn’t want too many variables on this. And this was just a study for fun. Like I did this for fun, which, you know, another thing. But

Jamie Martin
Challenge your brain and

Jim LaValle
but what was cool was after 30 days. So when we did the initial screens, for the most part, all of them had glutamate up here, acetylcholine down here, complaining of some memory deficits, right?

Jamie Martin
So kind of high just to be clear, like for those some who may are not watching, like the glutamate was higher than like this right

Jim LaValle
Acetylcholine.

Jamie Martin
in the CL choline is what you want to be higher.

Jim LaValle
You want that acetylcholine to keep the inflammation down in your brain. Right. It’s a it’s a it it kind of helps balance your your parasympathetic nervous system. Yep.

Now, thirty days later, we did the scans again. And it was funny because my partner in the institute, because we did MRI, CTs, I mean we did advanced imaging, you know, like five hundred images a day from twenty countries. So it was it was crazy to be in there. He could not believe the difference. He he’s he read them and he went, You actually changed their acetylcholine to glutamate ratio.

Eight out of ten people reported improved cognition and function and feeling better. And that correlated to the people that got their acetylcholine up and their glutamate down. So what does that mean? Right. Why did I do that? Well, it was to see your your brain tends to get in a a chronic excitatory pattern, and that tends to increase oxidative stress and damage to your neurons. So hey, let’s try to see if we can get that to come down.

Now it turns out 15 years later, there is a lot of advanced imaging to do everything from look at, you know, where your, you know, neurotransmitter activation, the like treatments that can show resolution or kind of your brain filling back out. Like in the case of people with chronic inflammatory response syndrome and looking at what’s called neuroquant.

Then you can actually do QEGs. You’re seeing all these advertisements now where people have a cap on. They got all these they got all these, you know, wires and bulbs coming out of them. So now you can start to measure reaction time, cognitive processing speed, right left brain communication.

And it’s interesting because we can see that there are nutrients that can increase cognitive processing relatively quick through through that type of testing. There’s a new one that actually shows mitochondrial function in the brain called cognivision. I I think that one’s out of Europe, but it but really interesting ability now to take a a snapshot of well, how’s your brain performing? Right. You know? It’s obvious if you feel like you’re, you know, hey, I’m foggy headed, and I I can’t think straight, right?

But a lot of us don’t realize and and and I think the one I’m most excited about is a simple venipuncture draw that will predict 10 years pre-symptom of dementia. What is it? And it measures entangled towel. Okay. And and so that test isn’t out quite yet. But it’s coming out and you know, obviously we wanna have that available for people. ‘Cause I think more people are scared about cognition than any other single thing.

Jamie Martin
I mean the idea of not having your memory or of not remembering is scary. You know, like that’s who we are, right? It’s like makes up our story. To lose those pieces is very I mean, that’s one of those things that’s kinda it’s like

Jim LaValle
Yeah.

Jamie Martin
Step back from that. I don’t want that to happen to me.

Jim LaValle
Right. No, exactly. And so that test, not only is that test interesting, there’s a peptide that will come on the market that will actually be able to be classified as a n a new dietary ingredient. So it won’t require drug testing. Okay that has been shown to stimulate what’s called progenitor cells, which they’re basically stem cells for your neurons in your brain. Okay.

And so what they’re showing is, you know, you can build neurons faster than you can destroy them. And that’s good news. Yeah. And just just think if you stop destroying them like because of working on your health, right? I’m eating better, I’m exercising. Yeah. Right. So to build progenitor cells.

Now, why is that so important? If you’re under chronic stress, you make a lot of cortisol for your brain. You block progenitor cells from budding and progressing to like granule neurons to fully pruned dendritic neurons. Okay. So when you’re under chronic stress, you block that. That’s why people are under chronic stress over time. They go, wow, man, I’m not thinking so clear. Right. Right? So this, so that ability to re stimulate progenitor cells, incredibly important.

And I’m I’m pretty excited about that. I you know, the the compound that’s gonna come out, I think it’s in December, is P6C. I don’t know what they’re gonna name it. Right. Right, right, but I get called to review a lot of this as chair of the International Peptide Society. It’s pretty exciting because if we can start to rebud the n our neurons and we can work on detoxification.

So for example, the we all heard of plasmapheresis. Yep. Now there’s a ionophoresis out of Europe that’s gonna be coming to the US that actually crosses the blood brain barrier and can clean up either the waste particles or the toxins that end up passing through the blood brain barrier. So I think well we went right to the heavy stuff, didn’t we?

Jamie Martin
We got right in

Jim LaValle
I just well, you asked me if I had anything new. So I was like, Well, I’m excited to share it with you. But I mean I kind of all of a sudden thought, wait a second, we’re getting pretty deep. We’re going pretty deep.

So but but I mean people need to know there’s hope and that there’s research going on and there’s peptides that can help, nutrients that can help, right? There’s nutrients that can really help the brain. obviously, you know, we’ll we’ll get to go through those. Yep.

But I think it’s important that people understand that. Your brain doesn’t have to age at an accelerated rate. Yep. Once again, you’re empowered to make change. Yeah. But you have to make change. Yep. You gotta you gotta be intentional about, hey, I wanna I really wanna help my brain. Yep.

Jamie Martin
There and that’s like so many things when it comes to our health, like what can I do, what’s within my control. And we’re gonna get to all of those things.

Jim LaValle
Exactly.

Jamie Martin
I wanna just go step back for a second. You’ve mentioned tau a couple of times, and I think it’s really important to explain what is tau. I know it’s like you hear about that in relation to Alzheimer’s or dementia or the tangles. So explain to us tau so that we can understand why of like you don’t want a lot of it, right?

Jim LaValle
Sure. Well, so let’s step back and go, Okay, how does your brain get in f neuro inflammation to begin with? Because that’s what’s triggering it, right? So that’s the next step. So you

Jamie Martin
So inflammation is not just in your b body, it’s in your brain as well.

Jim LaValle
Called neuroinflammation. So you have a blood-brain barrier. Yep. It’s one cell layer thick. I mean, it amazes me that the inside of our heart, our endothelium, all the blood vessels — one cell layer thick. It’s crazy. The gut lining, one cell layer thick, and then the brain. And so things can compromise that blood brain barrier, or things can pass through it.

Lipopolysaccharide is something that your gut makes when bacteria are breaking down. You release these from the cell wall of the bacteria. They release millions of particles from one bacteria. And that lipopolysaccharide can get through the blood brain barrier. This is one way it can happen. You could have an infection. You could have iron overload, right? Or mercury or something, right? So for whatever reason.

You activate microglial cells, which are your immune cells for your brain. They’re the big patrollers — the national guard, right? Yep. When you activate those microglial cells, they start to trigger a bunch of oxidative compounds, which act as basically free radicals, right? Peroxyl nitrites, superoxide anions, hydroxyl anions, a whole bunch of different ones. Yep.

Those end up damaging the neurons, and when the neurons get damaged, they start to break apart. Part of it is you get protein aggregation within the neuron before they really kind of deconstruct, right? So that aggregation of proteins is tau entanglement. You’ve got tau proteins, and so you wanna make sure you’re limiting that, because when the neuron dies, the life cycle of it is then the neuron dies and releases those proteins.

Proteins — alpha synuclein, Parkin, neuromelanin, laminin. Sounds like a bunch of big words, but they’re all components that get released and they activate the microglial cells again. It’s a vicious cycle.

Jamie Martin
So they just cycle.

Jim LaValle
Yeah. And that’s why people with dementia and Alzheimer’s all of a sudden seem to go down fast. They’re going down fast because that’s when you hit the accelerator button on the neurodegeneration.

And so, but unbelievably, I think we’re starting to be able to control neurodegeneration. I think there’s a lot that is getting done regarding that, because we understand it now. So that’s kind of the process — you get these tau entanglements, damaged proteins that then get released as the neuron dies. And when the neuron dies, you have cognitive loss.

Jamie Martin
Right.

Jim LaValle
And it starts to accelerate it, right? Because you’re getting more and more damage, more and more damage releases more of these components, which keeps triggering the immune system. And then people accelerate into their cognitive decline.

That’s why they’re giving a lot of medications, but honestly, medications haven’t done a whole lot. Right. I mean, you know, Namenda, those kind of drugs — they’ve minuscely slowed it down. My mother was a dementia patient. I feel like I have a right to talk about it because I lived that, watching her. I didn’t see much benefit on those drugs. So I think there’s a lot of other things that can be done.

Jamie Martin
Okay. We’re gonna get to that. I wanna talk about why thinking about brain health isn’t just for when you’re at a certain age, right? I mean, our brain health matters from the moment we’re born to the moment we die. We know that neuroplasticity is not something that’s limited to a certain time frame. You can continue to build neuroplasticity through your life.

So what’s your take? Why do we want to make sure that we’re talking about brain health now? I do know there are some things where 10 years before you have symptoms, there could be signs showing. So what should we be doing to be proactive about our brain health?

Jim LaValle
Yeah, that’s great. And I look, I think it starts at birth. A child’s brain is developing because of getting adequate DHA. They need the ability to feed the brain to build the brain. And then if the child was in the mother’s womb and the mother was anxious and nervous, the child’s nervous system gets set up a little bit to that extent. We know there’s an epigenetic correlation to that.

So what are the basics? Fish oils are really good. DHA in particular is fantastic for helping decrease neuroinflammation and repairing the brain, acting as a building block and keeping cell membrane integrity good. So if you’re not gonna eat a lot of fish, you should probably take fish oil. That’s one of the most basic, fundamental nutrients you need.

Controlling blood sugar is probably job one. Right. And what do we teach children when they’re little infants, babies, and toddlers? If you’re good, I’m gonna give you a cookie.

Jamie Martin
Here’s a treat.

Jim LaValle
I’m gonna give you a piece of candy. Right. Now, if we could give them a healthy treat — great. Give them a healthy treat. It’s okay, because yeah, it is a little bit of learned behavior to help out, right? But I think what’s happened is we’ve just as a society consumed way too much sugar. You and I know this is over a hundred and fifty pounds per person.

Jamie Martin
Yeah. And we know that sugar is a trigger for inflammation in the body — and the brain, right?

Jim LaValle
Well, exactly. So what happens is your brain uses a ton of glucose. So as you lose your insulin receptor’s ability to work with glucose, your brain can’t be fueled correctly. And then when you can’t fuel your brain correctly, the neurons can’t fire. Yeah, you lose mitochondrial capacity. Yep.

So here’s one of the tricks — when you know you’ve got a problem. When people say to you, I went on a ketogenic diet, I can’t believe how much better I’m thinking — all that tells you is their glucose and insulin relationship must be really screwed up. Because it’s natural for your body to use glucose.

Now, do I think ketones, beta-hydroxybutyrate — people take that? Yep. My gosh, there’s hundreds of papers on that. Yes, ketones can fuel and help your brain and your mitochondria. It’s really good. Yep. But you can’t get by when you’re insulin resistant. Much higher risk of dementia, especially when you’re type 2 diabetic from insulin resistance.

So we’ve got: take fish oils, make sure you’re not eating too much sugar. Yep. You gotta watch saturated fat in some populations of people. The ApoE 3/4 and 4/4 gene SNP people — they trigger a lot of inflammation when they eat too much saturated fat. Yep.

And I’m gonna fess up — I got all the bad cards. I don’t know how I’m winning, right? It’s like sheer effort. Because I’m an ApoE 3/4. And I noticed this before I tested for it, which was twenty, maybe twenty-five years ago. Nobody was even looking at that stuff. But I was an ApoE 3/4. I’m eating charcuterie, getting proteins and fats, staying off the carbs altogether. My cholesterol, my inflammatory signals in my blood were crazy. Yeah. So for ApoE 3/4 and 4/4, you gotta watch saturated fat. That’s something you should be aware of.

If you are an MTHFR gene SNP, that’s another important one, because you’re not gonna utilize folate as well, which helps in methylation, which means it helps you make neurotransmitters better. Yep. And that’s why there’s a prescription strength of methyl folate that is given to try to help with issues related to neurotransmitters. Yep. So that’s important.

And then B12 is important. These are all things. So if you’re vegan and you’re not getting any source of B12, it could put your brain at risk. So those are some early starts. And then of course, you’ve got to move.

Jamie Martin
Always. It’s always moving.

Jim LaValle
Exercise is important. It’s important to move. Move the lymphatics. And then if I had to go to the next piece — once again, lifestyle. I know we hear the term “manage your stress” all the time, right? I would just challenge people to measure their stress hormones. Like measure your cortisol in the morning.

Or if you wanted to do a four-point salivary cortisol — the Life Time Hub has that. They can talk with one of the coaches and go through a salivary cortisol to find out where your cortisol is, because cortisol is your major stress hormone. It’s made from your adrenal glands. You gotta get that straightened out. That’s important.

Now, why is that important? Because cortisol creates inflammatory cytokine signaling in the brain, and it blocks progenitor cells from budding.

Jamie Martin
Right. So again, we don’t want that cortisol too high, because it’s gonna block the phospholipids, the acetylcholine, and all those pieces. Okay.

Jim LaValle
More — okay, I know. We’re going deeper now. Come on. We’re going down. So the next piece is you should know what your blood pressure is. And I know everybody kind of doesn’t know their blood pressure. Ideally, you would do your morning and night blood pressure, because that’s going to show whether or not you’re reducing your stress hormones into the evening if your blood pressure goes down.

Jamie Martin
Interesting.

Jim LaValle
Either a dipper or a non-dipper is the way we call it.

Jamie Martin
So wait — you want your blood pressure compared to morning versus evening. How do you want your blood pressure?

Jim LaValle
Look. Morning higher than evening, but morning should not be high. Okay.

Jamie Martin
Yeah, right. So still higher but not —

Jim LaValle
I know we’re going through blood pressure and the heart a little bit later, but the blood pressure piece is important. And then where is your heart rate variability? Because heart rate variability is telling us the status of your vagus nerve, or vagal tone, which is coming from coherent signaling from the brain to the heart, to the nervous system, to the organs, to the tissues. Yep.

And so I know this sounds like wow, a lot. That’s why the brain is the command control center. That’s why you want to protect your brain. It is a little complicated, but at the same time, some of it’s kind of simple. There are things you can do.

Right now there’s a biologic called TB006. It binds up when your lipopolysaccharide goes up in your brain and you trigger your microglial cells — you make something called galectin-3. You also make that in your tissues, like in endurance runners. I checked their galectin-3 to see if it’s increasing their risk of fibrosis of their heart, right? Okay.

Jamie Martin
Got it.

Jim LaValle
So you measure galectin-3 — TB006 binds to the galectin-3 and stops the damage to the neurons. And they have phase 2A clinical trials showing significant drops in scores on their mini mental status exam. So their mini mental status exam goes from seventeen to twenty-three or twenty-four, which is good. They’re showing it to actually reverse or stop Alzheimer’s. TB006. Pretty important.

Jamie Martin
When you think about Alzheimer’s, you also think of people who have the gene for it, right? Like if there’s a genetic predisposition — where does genetics fit in?

Jim LaValle
Great question. So I remember I was lecturing at the Department of Neurology at the University of Cincinnati. And I brought this up. I said, you know, Parkinson’s and dementia — so in the case of Parkinson’s, for example, if you have the Parkin A or Alpha Synuclein gene SNP, you are at a thirteenfold increased risk of developing Parkinson’s. Yeah. And what percentage of people have that gene SNP array? Six.

 

Jamie Martin

Right. So small pretty relatively small percentage.

Jim LaValle

It’s environmental. I would say more and more with Alzheimer’s, they’re finding out that it’s environmental stress lifestyle, biochemistry. And yes, you can have a genetic predisposition. Or if you’re an Apo E34 or four four, you have a fourfold risk. Right. There are other gene SNPs that would confer that you have an increased risk. But remember, genes have to be turned on. Yep. So it’s

Jamie Martin

It goes back to the the things we talk about environment, lifestyle, stress, things

Jim LaValle

Exactly.

Jamie Martin

somewhat in our control. Yeah.

Jim LaValle

Yeah, exactly. Okay. We have to be careful about when to control everything. I know.

Jamie Martin

Right. I gotta let go sometimes. When we specifically talk about performance aging for the brain, like what does that actually mean for memory, focus, energy, mood, resilience?

Jim LaValle

Yeah, so when I’m aging, what I hope is that as I’m now I’m you know squarely in my sixties, second half. I’m I wanna make sure I’m able to focus, I’m able to remember, I’m able to be calm because that’s a lot of what happens too is we’re aging and we’re we’re losing some of our calming neurotransmitter effect because of the neuro excitation phenomena.

Jamie Martin

Interesting. Okay.

Jim LaValle

Right. So I get agitated more, crumpy old men. Right. Yeah, right. Exactly. Yep. So I wanna I want to be able to feel calm, feel focused, be able to think critically throughout my day, not just for an hour or two, and then I gotta go sit in my rocker.

I I really want to be able to perform where my brain is able to take in information, utilize it. Think clearly, not be depressed, not be anxious, right? And be able to sleep because that’s the other piece of cognitive health. Maybe the most important one is you know, do you have sleep apnea? Do you have disturbed sleep?

Jamie Martin

Right.

Jim LaValle

Big, big insults to the brain.

Jamie Martin

Well, and we’ve talked about this in other episodes, but sleep is that kind of that time, it’s restoration and repair of your brain. It’s when there’s like in your brain, there’s like this clean out process that’s happening at night. Like everything that you’ve done during the day or process. Like you think about the cleanup crew that comes in.

So talk I mean, when sleep is disrupted and on a regular basis for the long term, there’s real cognitive decline risks there.

Jim LaValle

What’s significant because if you’re if you’re having disturbed sleep, one what’s happening is is your circadian rhythm of your whole neuroendocrine immune relationships, right, patterns are getting disrupted because you’re awake when you should be in a restoration phase. Your body works in that circadian pattern, excites you during the day, repairs you during the night.

Literally your night when you’re sleeping, you are repairing your body. It’s interesting. The Chinese talked about this in Chinese medicine. Yeah. I mean, thousands of years ago, they talked about the Shen cycles, the cycles of when each organ is turning on and off during the course of that 24 hour day. And we all laughed at that 50 years ago. And now we’re all going, this is real. How did they figure that out? Right. Yeah. Well, you know, but but I think it’s important to understand that if you say for example you’re just hypervigilant. Yeah.

You’re gonna have a sympathetic dominant. So more adrenaline, more noradrenaline, more cortisol, more

Jamie Martin

Might or flood.

Jim LaValle

fight or flight, and that is going to damage your neurons. I mean, it’s good to have fight or flight. Yep. But fight or you

Jamie Martin

Acutely or not chronically.

Jim LaValle

have two sides to your nervous system, right? You’ve got sympathetic and parasympathetic. Parasympathetic is supposed to be anti-inflammatory and it’s kind of running the steady state. Yep. Breathing deep at rest. And then you’re supposed to have a a pulse of sympathetic when you need fight or flight. Yep. Right? It’s supposed to be a pulse. It’s not supposed to be sustained. Yep.

And so there’s something called the vagal break. The vagal break, right? Where the vagus nerve and the vagal tone is there when you have enough acetylcholine to say, hey, hey, hey, hey, hey, slow down over here. It’s not a white tiger.

Problem is with chronic, like I did in that MRI, going back to the beginning of our talk when I did looked at those functional MRIs. You lose acetylcholine and now you’re all excitatory and you start to really damage tissues, and cell membranes and neurons and neurotransmitter receptors. And so that’s why it’s such a it’s it’s just fascinating of how you can really repair it, but also how you can really damage it.

And that’s also why I like people looking at resting heart rate. Yep. Why I like them looking at heart rate variability, why I think they should measure their blood pressure. Because all of those things indicate: am I sympathetic dominant? Now, if you go to bed at night and you can’t fall asleep, and once you do fall asleep, you wake up at three in the morning, chances are you’re you’re hyper-aroused.

If you have apnea, which it can be structural, right? You could have a jaw issue. The airway could be reduced. Yep. Right? Yep. There’s a lot of different or it could come from your central nervous system called central apnea. So when you think of that, either way it goes, with apnea, what happens is the airway closes, you get oxygen deprived, the brain freaks out. Yep.

And the vag that vagus nerve has to react and say, Wait a second, heart, brain, you gotta go. You gotta pause And what happens? Heart rates go up to a hundred and fifty, hundred and sixty, hundred and seventy beats for that episode until it gets oxygen. And so when I do a sleep study on people, they’ll see how many episodes of that was occurring. Right. And and and I think that’s a lot more common than people think.

Jamie Martin

And are each of those disruptions potentially I mean you think about that, it’s interrupting the processes in the brain that are supposed to be happening at night, like the natural processes with the to support the circadian rhythms, the cleanup, the repair.

Jim LaValle

Without a doubt, when you disrupt all that, now I can’t rebuild my serotonin pools. I can’t rebuild my dopamine pools. Yep. Certainly can’t rebuild my adrenaline pools. So what what’s the process people go through? They go through, hey, I’m okay. To gee, I’m feeling a little bit anxious, not thinking clear, while I’m feeling tired and wired. Yep. And then you finish off with tired and flat. Yep. I’m just fatigued. Mm-hmm.

And that’s partly because of sleep, partly because of no repair due to the, you know, to thus to that whole cyclic circadian pattern. The master slave clock is in the pineal gland. It’s called, you know, the superchiasmatic nucleus.

Jamie Martin

I’m like, I know it’s like s C N, right? Like it’s a little

Jim LaValle

Superchasmatic nucleus. You say that’s three times real fast. Exactly.

Jamie Martin

Exactly.

Jim LaValle

Exactly, right? But but that superchasmatic nucleus is driving how your glucose regulation is going to be for the next day. Yep. So even if you ate well, but you’re not sleeping well and you’ve disrupted your superchasmatic nucleus, I’m still CM morning blood sugars higher than I probably should be. Right. Right.

So they think it’s really important to understand that. And and look, this doesn’t include environmental burden vectors or infections that can accelerate all this too. So we know I love the example of you know, hatters from the eight you know, seventeenth, eighteenth centuries. Right. So the the the people that made hats, they had a steamer. Remember you’d see in the movies or steaming the the brim of the hat?

Jamie Martin

Get it nice and tight.

Jim LaValle

What was the solution they put on that?

Jamie Martin

You’re asking the wrong person. What is it like?

Jim LaValle

It was a mercury solution. Not bad. Mercury, steam it, breathe it.

Jamie Martin

Yeah.

Jim LaValle

Breathe it in. What was the saying that came from that? Matt is a hatter.

Jamie Martin

Mad as a hatter. Okay. Makes sense. Because it was essentially the environmental overload from that.

Jim LaValle

Mercury intoxication going into the yeah, it’s mercury intoxication damaging your neurons, which we know it does. And so the my point is is that like some of the innovations that we have now is like learning about how do we test for things like heavy metals. Right.

There’s no it’s it’s finally being recognized. I can’t understand. Like 2005 veterans normative aging study showed that lead was being deposited in more war two vet’s bones and that could be affecting your cardiovascular health.

We we’re now seeing that for example in neurodegenerative disorders, there’s a clear correlation to environmental exposures. Yep. Right? Yep. So there’s that piece. And then of course, when that blood brain barrier is not strong, you get an infection. It can be a it could be a big problem. Right.

Jamie Martin

Can be a major issue.

Jim LaValle

So I I I think it’s exciting because I think there’s so many things you can do to support brain health. Yep. At at the same time it it it’s more than I’m gonna do a peptide and that’s gonna fix it. I I think that there’s new things that are fantastic and it’s gonna be really I think we’re gonna have more power to protect our brain in the next decade than all of all of history. Right.

I mean, it’s amazing what’s going on between being able to soak up galactin three. Right. Like even modified citrus pectin, you can take it and it and it binds to galactin three. So if you’re very rare, but if you’re a person with prediabetes or diabetes, you make a lot of galactin three, you can soak that up. And if you’re soaking that up, that’s gonna reduce your risk of developing Alzheimer’s, right? Right.

So I think there’s some really cool interventions like that. And then there’s the obvious interventions. Right. Right. Medicinal mushrooms and, you know.

Jamie Martin

Well, and those are kind of on the nutrition supplement side, right? So we’ve talked a little bit already about, you know, the fish oils, the DHA, B twelve. You know, you just like what are what are some other examples in that space?

Jim LaValle

Well, you need adequate vitamin D status, right? Magnesium is super important for just general circulation and regulation of glucose and ATP production. You know, you could think of maybe modified fish oils too, the SPMs, like the pro resolvins, if you wanted to think of that. Yeah.

Those are probably some of the more important just straight nutrients. I mean, obviously zinc, there’s a reason because of glucose regulation, but because I could almost think of a reason for every essential nutrient, they’re essential for a reason. Affect

Jamie Martin

That’s why we need that.

Jim LaValle

all parts of our body, right? I mean it’s gonna happen. Yep. But I’d say things like medicinal mushrooms, you know, like you know, you know, lion’s mane, you know, great in terms of supporting immune function as well as you know, helping with serotonin production. Really good.

S like Gensinocyte R3, otherwise known as synapsin, dampens microglial cell activation. That’s one of the other ones that’s currently under studied in the preliminary trials on that one. Actually showed a 40% improvement in cognitive processing within the first couple doses. So that was powerful.

Obviously there’s the standbys of, you know, hey, does Ginkgo work? And sometimes sometimes ginkgo’s great. Right. Other times you don’t get much out of it. Yeah, it

Jamie Martin

It depends on the

Jim LaValle

depends on the individual. You gotta you gotta see like how I would do it is maybe you have a brain memory game that you’re using. Maybe you wanna do this for yourself. And you only can score this much. And then you start doing some things for your brain and you go, Wow, wait a second, I just proved it. I made a leap.

And then you could go to QE E G and go, Hey, is there better cognitive processing? Is there better better millivolt, you know, going through the brain, right? 300 is kind of the standard that they go, hey, you really should be here. So I then you could go to that.

And then of course there’s really exotic things you can do, but then you could also do a blood test and you can find out, are you insulin resistant? Are you making bade actor lipids? Where is your glucose and insulin together? Where’s your kidney function at? Because kidneys actually correlate really well to potential risk for Alzheimer’s.

And you know, it’s interesting. There’s these and I know we’re gonna talk about it when we talk about the nervous system, but I’m just gonna bring it up is that there’s these rest proteins. Isn’t that where do we call them rest proteins? Tell me

Jamie Martin

Yeah, okay.

Jim LaValle

more about those. But it basically if your body is more you know, makes those, you’re more prone to be able to turn off excessive excitation. And that’s where they found people that were cognitively sharp and lived longer was with those folks that had the rest proteins.

Much like I know we didn’t get to to you know, to this yet, but there’s other issues like when we talk about autoimmunity. Yep. There’s certain little interesting nuances about genes or proteins that are made that help people to live healthier longer.

Clotho is go is the next big peptide that’s going to be coming out as a mitochondrial peptide cell regulator. That’s good. I’m telling you right now, that’s the one for 2027. Okay. Ever you’re gonna hear it on every social media post about cloth.

Jamie Martin

So

Jim LaValle

K-L-O-T-H-O. Cloth. Okay. Yeah. So so the so yeah, pretty wild, right? So the other nutrients, so the ginsenicide R3, I mean, we studied that with Corvette Race team. Yeah. You get under stress, remember, you get under stress, your br y your b core body temperature goes up. Your brain coherence goes down, your reaction time falters.

So that’s when we develop that. And actually, I mean, we’re when we first developed it as a nasal spray, because I as you know, I I I research, I invent, yep. Like another hobby.

Jamie Martin

Or a hobby.

Jim LaValle

It’s like we like to do. No, I mean it is, it’s kind of a hobby. I I I I like to look for these kind of things. So when we use the nasal spray, a lot of people and I just saw it on a post and I had nothing to do, I had no idea. This medical doctor’s going, this is limitless. I went, I don’t know if it’s that. But it really does help with downregulating microglia. So ginsenicide R3, real important

Jamie Martin

And that’s the synapse, right?

Jim LaValle

synapsin, yeah, that’s really important. And then Sustantia tuberlosa, another one that’s a big one for the brain, it’s gonna be coming out this year.

And then of course you’ve got things like acetylcarnitine, you know, you know, utilizing the different amino acids that will build your neurotransmitters. Yep. Very helpful. T crin, for example, which is great for dopamine. So people improve their focus on it without getting stimulated. So there’s a lot of different nutrients that I think are just, man, waiting to come out into the market.

Jamie Martin

Be seeing more of this.

Jim LaValle

Yeah, I think so. I think I think it’s going to be a big it’s just continuing to be a bigger, bigger interest ’cause right, the the baby boomer but are they’re all coming of age now. I’m in it, you know.

Jamie Martin

Yep, and we wanna again stay as healthy as we can for as long as we can.

Jim LaValle

Gotta stay smart.

Jamie Martin

Mind, body, right? Right. Okay, so I wanna talk for a second about exercise because we know that exercise is one thing that can stimulate BDNF, brain derived neurotrophic factor, right? Like why does that matter?

Jim LaValle

Well, BDNF is going to help with that renewal process for neurons, right? So the other thing that exercise does is it helps to reset the nervous system. Now, there’s people that train really hard for really long periods of time. Yep. Th that’s because you have a personal goal or you’re competing. That individual needs to really work hard at their recovery to get their nervous system to cool back down.

Right. So that’s why whether you get in a cold plunge or you get the cooling jackets, right, to kind of kinda calm things down, doing some breathing, you know, fig figure out what you need to do because that’s pushing the body really hard and you may not be recovering enough. Right.

Jamie Martin

And you’re talking specifically like endurance events and

Jim LaValle

Yeah, we’re endurance events. Yeah, long hour and a half, even an hour and a half, like hit training that’s an extended period of time. Yep. That’s why wearing the wearables are so important to help you say, where am I at my recovery? Where am I at on my HRV? If my HRV is going down, what did I do last week? Yep. But it’s got to look at it as a trend, not just one day. Right.

But the but I think the biggest factor to this really is that you gotta be you gotta listen to your body. Yeah. Listen to your body. Measure what you can. Make decisions about how hard you’re training. Look, if you’re a pro athlete, you’re getting paid, you know, obviously a lot of money in order to use your body. That’s that’s one thing. Yeah. When they’re done with their career, they’ll have to work on their recovery.

But for us who maybe have daytime jobs or already under a lot of stress, family, and we’re training hard, harder you train, the more you need to recover. Right. You’ll hear me th say that a million times.

Jamie Martin

Absolutely. Are there any other factors, you know, we’ve talked about the obvious nutrition, recovery, sleep, stress, exercise,

Jim LaValle

Hormones.

Jamie Martin

hormones we need to be thinking about. The other thing I want to make sure we touch on too is just the the idea of like social connections, purpose, meaning, and that element of this when it comes to cognitive health. So let’s do hormones and then jump into that.

Jim LaValle

Yeah, so hormones are important because as you decline with hormone production, especially women with estradiol, up the menopause, you know, men and women will lose some brain size. But actually when women lose their estradiol, they accelerate their loss of no brain volume. And that’s why we hear, you know, more women than men have Alzheimer’s. Yeah. Right? Mm-hmm.

And it’s also interesting because they bec and it’s like, well, why is it so significant? Why do they have such a higher percentage? Yeah. Well, women have two X chromosomes. On the second X chromosome, it’s called an XIST protein that when you trigger that because of inflammation, duration, and stress, it starts to accelerate the cognitive loss.

Jamie Martin

Got it. Right. So that X X versus the XY. Got it.

Jim LaValle

So I think it’s pretty interesting. It’s the same thing. I mean, it’s the same process that happens in autoimmunity, actually. So ’cause when you think about it, any inflammation is going to be, you know, a negative when it’s excessive. So even though that was found in looking at autoimmunity, we’re it’s like, well, but it’s also there triggering neuroinflammation in the brain. Yeah.

So I think there’s gonna be a lot more studies on what’s going on with like those type of things that are gender specific on that second X chromosome or for men or you know, the or for men on the Y. So X Y versus XX. And so I think that’s I think that’s fascinating how that’s gonna happen. Well

Jamie Martin

And as we just continue to innovate and learn more and ge able to get more specific.

Jim LaValle

And I think we know that women that use estradiol use by I I say estradiol specifically because I think they should be using biodentical estrogen as they age. Cognitively sharper, skin’s better. You can ask any nurse that worked in a nursing home. Right. They could walk in and tell who was taking even back then premarin, right, which is the conjugated estrogen and who wasn’t.

Jamie Martin

Yeah. Just based on like their skin t like tone, right? Wasn’t it? Like or like thin or elasticity. Yep.

Jim LaValle

Exactly. So I I think the hormone piece for men and women both, right? When men lose testosterone, you know, they get more insulin resistant. They have more issues that drive cognitive function. Women, it’s even a little more direct with the estradiol though.

Jamie Martin

Right. And it’s a little bit can if you’re correct me if I’m wrong, but like for men it tends to be a little bit more gradual, where for women it kind of like the kinda hit that perimenopause, postmenopause, and there’s a more significant drop, more of a cliff, right?

Jim LaValle

And that cliff is but it’s it’s great you mentioned it. That cliff is because women make anti inflammatory glycans in every cell in their body. Right until menopause. Yeah. And

Jamie Martin

And then that ex

Jim LaValle

when that yeah, so as soon as estradiol is turned off, you you switch on and you’re making pro inflammatory glycans, which are one of the four main structures of your cells. Every cell. So it’s like it’s a big deal.

Jamie Martin

No wonder you feel the difference, right? Or maybe

Jim LaValle

Exactly. Of course. Of course.

Jamie Martin

Okay. So last kind of factor I want to talk about, I already alluded to it, is like this idea of connection, purpose, mental challenges. You already talked about doing puzzles, but I do think we do know like when people the lone loneliness epidemic, people who are lonely tend to like not be as healthy both physically and mentally. So why does that matter?

Jim LaValle

Well, I think first of all, we’re social we’re social beings. Yeah. We’re hurting the most. Yeah. We’re meant to feel connection. Yep. To feel, you know, what the Native Americans said, agape, right? Like love. Yep. Universal love. You know, we’re meant to feel joy. And those are p we we know that positive feelings change your brain chemistry. It’s been measured a bunch. Yep. Cortisol negatively changes the output on your on on your feelings and and and what’s going on in your brain.

So social connectivity to me is you know it’s it’s it’s really interesting when you come from I I came from a basically Italian family and our family reunion would have like three hundred people at it, right? And everybody’s talking to each other and everybody’s yelling at each other. But at the end of it, you’re all there together. Yep. You’re all talking.

And when I just came back from Europe from that s from the Swiss Alps that you know, collecting botanicals. You know, it’s it’s still that way. There’s tables in the street and there’s communities of people. Yeah. That you don’t see that that much anymore. We’re all become, you know, we can get our del food delivered to our door. We get in and out of things quickly.

And that’s why I think you know, I I have an appreciation for a lifetime because of the Aurora group. Right.

Jamie Martin

Bring it together.

Jim LaValle

I I think what’s wonderful about Life Time is that it’s a place where people of like mind. Hey, we’re interested in fitness. Yep. You can meet other people, but even for those folks in the Aurora group, which is, you know, don’t call it

Jamie Martin

Kind of our healthy aging population.

Jim LaValle

Thank you. Thank you. Cause I’m like, come on, I’m one of them. So I my my but my point is is that I think it’s wonderful when we sit in meetings and I get to hear about plans that are being done to bring seniors, I said it, seniors together to be able to enjoy, have a community, have a place that they can feel like they’re a part of something. Man, that is that’s powerful. That’s really powerful. Yep.

And it it says a lot for, you know, the he you know, quote, you know, the Healthy Way of Life Company. It says a lot that that’s not, you know, it’s just not a slogan. No. It’s yeah, yeah.

Jamie Martin

It’s actually happening. Well the goal is bring people together, help people feel like they belong, right? ‘Cause that’s really what we all want, right? Is to belong to something bigger, right? Yeah.

Jim LaValle

We do, you know, unless we’re like some, you know the the rare hermit who I would say that if they find somebody they can communicate with, they no longer want to be a hermit.

Jamie Martin

Right. Right. Gosh. Okay, Jim, we covered a lot of ground here. We talked a little bit about what’s coming in this space from measuring, you know, being able to measure your brain health, kinda where you’re at, plus what we can like new nutrients and things that are gonna come. We’ve talked about the foundational things that we always talk about. Did we miss anything that you wanted to make sure to cover when it came to

Jim LaValle

Exercise or hit sleep. Try to understand. I know we’re gonna do a thing specifically on the nervous system, so I’m gonna save it a little bit. Just try to do things that help you to stay calm but focused. Yep. That’s that’s the key.

Jamie Martin

Okay, that’s a little teaser for when the nervous system episode is coming. It’s coming soon. So all right, Jim. If people want to learn more about MIORA, they can visit MIORA dot lifetime.life and find more of these podcasts at experience life.com forward slash podcasts. All right, we’ll talk to you soon.

Jim LaValle

Remember all that, that’s pretty impressive. I know

Jamie Martin

I’ve got it. It’s up here.