Dr. Rhonda Patrick reveals saunas cut men’s all-cause mortality by 40% with 4–7 weekly sessions, linking heat shock proteins and FOXO3 to longevity, while debunking alkaline-cancer myths—cancer cells exploit lactic acid for survival. Her 30-day VSL#3 probiotic trial boosted gut biodiversity, countering antibiotic damage like MRSA she cured with natural remedies. Exercise-induced lactate may treat TBI and Parkinson’s, but genetic variations (e.g., vitamin D metabolism) dictate responses. Heat training enhances performance via blood flow and protein protection, though risks like surgery complications linger. Cold therapy aids recovery post-injury, but stem cell injections remain unproven long-term. Nutrition and stress resilience shape health far more than oversimplified trends. [Automatically generated summary]
I've heard of it happening after you've exerted yourself, like very strenuously, like after a marathon or something, and then you drink a bunch of water.
And the salts that you basically excrete out, like you're totally imbalanced.
Since you've been here last, boy, I've read so much stuff about the sauna, about the benefits of the sauna, and then you published that thing saying there's a 40% decrease in mortality on basically on everything?
I wrote an article on some of the health benefits of the sauna, and I predicted that I thought it would play a role in longevity based on some other evidence.
And then this study came out showing, indeed, that there is a link between sauna use and a decrease in all-cause mortality.
So people dying from cancer, from cardiovascular disease, from a variety of different diseases.
Um, it's, you know, it doesn't get as hot as like a typical dry sauna where, you know, the air is, it's like 174, 79 degrees Fahrenheit, which is pretty damn hot.
That's like, like in my gym, that's, that's pretty, pretty much the temperature.
It's like 170 degrees Fahrenheit.
So that's hot.
Steam showers, they get hot, and I definitely feel my heart racing.
So what happens when you're in heat is your heart starts to race, much like cardiovascular exercise, where your heart starts to beat between 100 and sometimes 150 beats.
So it's pretty fast.
And part of the benefit of that is you have increased plasma and blood flow to the heart, so the heart's actually doing less work than it normally would do.
And that's part of the cardiovascular benefits that are associated with exercise and sauna use.
But the sauna, in addition to that, has other effects.
So heat stress is a stress, as is exercise.
And the stress activates all these stress response mechanisms in the body.
And that's really good.
And that's part of the benefit from exercise.
It's part of the benefit from any type of, you know, good stress.
So heat specifically will activate something called heat shock proteins.
So it's a gene that makes something called heat shock proteins.
And they're a class of proteins that are activated by heat.
So when you exercise and your core body temperature raises, they get activated.
And heat shock proteins are pretty awesome because they are able to prevent a certain type of damage that accumulates in our cell from happening.
And if you think about the causes of aging, it's an accumulation of damage that's happening in the cell, like if you're looking at it at the molecular level, the cellular level.
And part of that damage occurs in proteins that we make, you know.
So genes are DNA is the genetic code.
It makes RNA. RNA gets translated into proteins.
And proteins are doing all the work inside of our body.
So for example, glutathione peroxidase is a very potent antioxidant.
It's an enzyme that's using glutathione to do all this great antioxidant stuff.
That's a protein.
It's the type of protein.
So proteins inside of our cells, as we age, they start to dysfunction.
They start to aggregate.
They aggregate in our blood vessels.
It can lead to plaques.
They aggregate in our brains, amyloid beta plaques.
And this happens, you know, this increases as we age.
But heat shock proteins prevent that from happening.
And so heat stress activates them.
And when you have heat stress and they're activated, they're actually activated for a long period of time.
In some cases it can be like a couple of weeks.
So it's kind of like you do this heat stress and then two weeks later you still have these activated heat shock proteins which are preventing all this damage from accumulating in your cells.
What's really interesting is that if you look in like worms or flies, You expose them to one heat shock, meaning you increase the temperature for 15 minutes, and it increases their lifespan by 15%.
So that's pretty cool.
Also, people that have a certain variation of the heat shock gene that makes these proteins, that makes them active all the time, They're more likely to be a centenarian.
So they actually have a higher chance of living to be 100. So there's definitely evidence that these heat shock proteins are involved in longevity.
We know the mechanism.
We know that heat helps activate them, and they're doing all this good stuff.
They also prevent muscle atrophy, and that's been shown in mice, for example.
If you make a mouse immobile, So it can't move like its hind limb, for example, for like seven days and you let it like use kind of like a sauna where it's like a whole body heat shock for 30 minutes a day.
They are able to regrow their muscles faster and they have less muscle atrophy than mice that are not exposed to the heat but are also immobile.
So I think the heat shock proteins are one possible way.
It plays a role in longevity.
And the other way is by activating this other pathway that's really, really awesome.
It's kind of cool because this VOXO3 gets activated by exercise.
It gets activated by heat.
And what it does is it activates this whole host of genes.
Genes that are like glutathione, antioxidant genes.
It activates genes that are involved in repairing damage to your DNA, which can lead to cancer.
It repairs damage to your entire cell, which can lead to the cell dying, and if that happens in your stem cells, your stem cell pools go down.
So FOXO3, it's doing so much.
And FOXO3, I've actually worked with it in worms, some of the early research I did in aging.
We could take a worm and make it always have it, by genetically engineering it, we could make it always have an active FOXO3. And these worms live between 50 to 100% longer.
So the worm lifespan is usually around 15 days, but it could live to a maximum of 30 days when you have it always having this FOXO3 reactive.
And humans that actually have a variation in this gene.
So variations in genes are what makes us all different, right?
So we all have different variations of genes.
And if they happen in a percentage of the population that's more than 1%, it's called a polymorphism because it's not just random mutation.
Well, this FOX03 is a polymorphism because quite a bit of the, you know, percentage of the population has a form of it that has it active a lot.
And those people that have it have a 2.7-fold increased chance of living to be 100. And what happens, people that have this often are able to handle stress better.
So they're able to, for example, you've heard of people that are like 100 and they've smoked cigarettes.
And you're like, how have you smoked cigarettes for 50 years and lived to be 100?
Like, what's going on there?
Well, oftentimes people have this overactive FOXO3 where they can handle the smoking stress, they can handle, you know, drinking a lot, they can handle just a poor lifestyle because they're able to detoxify things, they're able to clean up the mess, you know, get the damage out and so it's not accumulating and doing all this bad stuff.
So, sauna activates that.
And I'm totally speculating here.
This wasn't shown in the paper.
The paper was an associative study.
So, it basically looked at these about 2,000 men that were using the sauna and then said, okay, well, in a dose-dependent manner, meaning the more often they use the sauna, the less likely they were to die of cardiovascular diseases.
Pick your choice of heart attacks, coronary artery disease, coronary heart disease, atherosclerosis, et cetera, et cetera, cancer.
So these were all down in men that use the sauna more frequently.
So I think that's pretty cool and I really think part of that is that hormetic response where you're stressing your body with heat to activate these heat shock proteins or FOXO3 and other things that are then Active for a longer period of time and help you deal with stress, with the stress of aging, with the stress of breathing in oxygen, which does a lot of damage.
Just breathing in oxygen and the way we make energy, we use oxygen and we eat food and that's coupled to make energy and that process generates damage just as a metabolic byproduct.
So I think that's really cool that the sauna is able to activate those really important genetic pathways.
I think that I'm a little wary of hyperbaric chambers because it does create damage, having more oxygen.
But it really depends on the context.
Are we talking about someone that isn't getting enough oxygen to their brain because the blood-brain barrier has been damaged?
So in that context, hyperbaric treatment can help.
Get more oxygen.
So I don't know if hyperbaric treatment is great for like your everyday person because it does it does create damage more damage Well, that's so weird that it creates damage because it's being touted as something that helps repair damage Like that's where athletes use it.
They use it to heal broken bones quicker injured tendons surgery Well, I mean, yeah, that makes sense in a way, too, because you're, you know, you're carrying, your red blood cells are carrying, you know, more red blood cells are carrying goodies to that side of damage.
So it's kind of like a trade-off, you know, but oxygen itself does cause damage.
Like, it just, I think it just depends on the context.
I think some folks even use it for anti-aging, if I remember correctly, that there's some proponents of anti-aging treatments using the hyperbaric chamber on a regular basis.
Joe Namath was a very famous football player from the 70s, who, a lot of damage, like every football player, a lot of concussions, and apparently he has been using the hyperbaric chamber.
I should say it right, because I'm not sure if I'm saying hyperbaric or hypo-baric.
But Joe Namath has been using, I believe he's been using the Hyperbaric, and there was an article on it that he...
Remarkably, because he's in his 70s, and most of these football players, I don't know if you saw that real sports piece with Bryant Gumbel, because we talked pretty extensively about brain damage last time you were here, because it was right after I brought you to a UFC, and you and Dan came back all scrambled.
You were like, what the fuck did we just watch?
But the hyperbaric chamber has been helping Joe Namath deal with the relatively minor reactions to concussions that he has had because he's pretty lucid.
He had some substance abuse problems and things along those lines that I'm sure probably affected his cognitive function as well.
But as far as a 70-year-old former professional football player, Doing pretty well.
So it makes sense because in the sense of oxygen is required for metabolism.
And in order to repair anything, metabolism meaning you need to make energy.
So in order to repair a ligament that's been wounded or brain damage, anything, Oxygen is part of that component to generate energy.
Oxygen plus food, whether that's carbohydrates or fatty acids.
Your energy source doesn't matter.
Those two things coupled together is how we make energy.
So the more oxygen you have in, and that's part of how cardiorespiratory fitness comes into play too.
People that can breathe in more oxygen and they're able to actually make more energy.
In that sense, it would help because one, you're able to get the oxygen to your cells, which have mitochondria, which is where the energy is made, the oxygen coupled with the food that you take in.
So that's one possibility that makes sense.
And the other would be, like I said, with the brain injury, where you're In some cases, people can't.
Their blood-brain barrier is damaged, and so they're not getting enough oxygen into the brain, and so the hyperbaric treatment can help get more oxygen.
Because you have to get the oxygen to the brain to make energy.
Your neurons need oxygen to make energy.
So that makes sense.
But again, There's always a byproduct of that metabolic reaction and that byproduct is damage in the form of oxygen superoxide, which is very reactive, or hydrogen peroxide.
Both those things are produced as a byproduct of using the oxygen for energy.
You know, you always like think of mountain people as like these like really hardy folk that just seemingly can just kind of get by under extreme circumstances and conditions that us low-lying sea level folk struggle at.
You know, that's the reason why athletes go and train at high altitude.
And have you seen those tents that people sleep in?
It's an interesting thing that a lot of fighters started doing.
They start sleeping in these high altitude tents.
Because apparently the way to do it best is they think you should live at high altitude but train at sea level.
So if you could, like, live at a place like Big Bear, where you're at 5,000 plus feet above sea level, and then go down to, say, like, you know, Santa Monica or something like that to train, where you're at sea level.
So that way you would be able to put out more work output, because the fact is it's a more oxygen-rich environment, you can train harder, you'll have more energy, and then when you recover, you're recovering in a low-altitude environment, and apparently that's the best combination as far as athletic results.
See, the problem is these protocols, they move with the tides.
People, they have these ideas that you've got to do it this way, and then they change it, and then you've got to do it that way.
I sent you an article on cold water immersion, because some gentleman had written an article on cold water immersion and the negative aspects of cold water immersion.
It had benefited somewhat.
It benefited endurance athletes, but it showed negative consequences for strength athletes.
And I found that to be pretty fascinating, too, because I know that there's definitely negative or definitely rather positive benefits of cryotherapy, which is a different situation.
It's not cold water immersion.
You're dealing with 250 degrees below zero for short periods of time, and your body develops, produces cytokines, right?
Is that what I say?
Which are a type of protein as well.
And apparently your body really only wants to produce these when it's cold as fuck.
So, I first became interested in this cold shock, as the scientists called it, whether that's by cold water immersion or cryotherapy or whatever, like last January when a paper came out that showed cold shocking can regrow synapses that are lost.
And I was like, whoa, that's really cool.
Because synapses are what connect two neurons together.
And it's essentially when you learn something, when you experience something, a synapse forms.
And that's a memory.
Whether that's a memory of an experience or it's a memory of something that you learned, it's a memory.
And as we age, we lose synapses.
We lose those memories.
You know, that's worse with neurodegenerative diseases and things like that.
Traumatic brain injury, you lose synapses.
And so I was like, that's really cool that something about the cold can regrow these synapses.
Well, it turns out that, like, scientists started looking at this by looking at hibernating mammals.
They're looking at bears and, like, other rodents that...
that hibernate or squirrels I think they were and what they found was that these during hibernation when it's cold they lose between 30 to 40 percent of their synapses and then when it warms up in the spring they totally regrow them back and so their scientists were like whoa what's going on there so they further did some studies in mice and they showed that if they cold shocked a mouse by exposing it to like What would be like a refrigerator, so like 40 degrees Fahrenheit, for like 30 minutes.
These mice were able to induce what's called cold shock proteins, which are...
I talked about the heat shock proteins.
Well, cold shock proteins are part of the stress response because cold is a stress.
And so most things shut down when you're cold, except for this class of proteins called cold shock proteins, which go up.
And apparently there's one specific one called RBM3 that goes up in the brain.
It also goes up in muscle.
And it is able to basically regenerate these synapses because it It makes more protein.
So it sits there like on the dendritic spine, which is part of the neuron that talks to other neurons, and it's able to regrow the synapse.
So anyways, I thought that was super cool.
They were able to show that in mice after just one exposure to this cold shock.
The caveat is that the core body temperature of these animals went down to like 60 degrees Fahrenheit.
Their core body temperature is normally like 98.6.
So that's a huge change in core body temperature.
If they expose them twice to this cold shock, they're able to increase the expression of this RBM3, this cold shock protein that regrow synapses for Six weeks in their brain.
And then they went on to get these mice that were genetically engineered to get Alzheimer's disease.
They exposed them earlier in their life before they started having symptoms.
They exposed them twice and it totally delayed the symptoms.
They didn't have the cognitive deficits and behavioral deficits.
Their brains didn't have all the amyloid plaque accumulation and it extended their lifespan.
So, I read the study and I was like, this is freaking cool because it potentially has huge implications for brain aging in general, for neurodegenerative diseases, for traumatic brain injury.
Of course, it hasn't been shown in humans and I have no clue.
The question is what the minimal effective dose of cold is.
Can you sit in a cryo chamber that's like a minus 160 degrees Fahrenheit for two minutes and Activate this cold shock protein.
I don't know.
That hasn't been shown, but it'll be really interesting to find out.
You mentioned the differences between, you know, cold shock and its effects on athletic performance, recovery, even muscle hypertrophy.
So the literature out there is kind of confusing because it really...
There's so many different factors that come into play when you're doing a clinical trial like this, where you're, you know, having an athlete that's either trained or untrained, engaged in some sort of physical activity that's either very strenuous or it's moderate, and then you're doing a cold shock, whether that's, you know, cold water immersion or it's cryotherapy.
When you do the cold shock and then what you're measuring and when you're measuring it.
So there's so many different parameters that you have to look at because they can have different effects.
And part of the reason for that is when you do exercise, it is a stress and the stress that happens.
So you're basically forcing your muscles to work harder, which means they need to make more energy.
So, you know, that can cause more damage.
This damage happens because of the oxygen byproducts, but also inflammatory molecules get made, pro-inflammatory molecules.
So, you know, and when those things happen, the response of the body to that is to make So, to make anti-inflammatory molecules, and this has been shown empirically if you look at athletes that train really hard, within, like, immediately after training, there's a huge increase in these pro-inflammatory cytokines, things that can, if they go out of control, can cause more damage, damage to muscle tissue and cartilage and things like that.
But then an hour later, there's a huge response, an anti-inflammatory response, that cytokines that are able to promote wound healing, they're able to regenerate tissue damage and things like that.
That happens an hour later.
And that's happening because of the stress that's induced.
But if you're looking at the dose, the exercise dose, that really sort of dictates how much of that bad stuff that you're going to make.
So if you're a competitive athlete, or if you're a professional athlete, or someone that's really, really training hard, you tend to actually make Much, much more of these pro-inflammatory cytokines like IL-1, beta, TNF, alpha.
And what happens is these professional athletes make so much of it that it kind of spirals out of control and causes muscle damage and tissue damage.
And so it's often called overtraining.
So, in a case like that, and this has been shown with cryotherapy, that if you do cryotherapy immediately after very strenuous exercise, in some cases, in one study they were doing a very strenuous, like, heel training, where they were sprinting up hills and doing this really, really strenuous activity.
They did the cryotherapy immediately after, and what they found was that these athletes had less muscle damage, so they measured Different biomarkers for muscle damage.
And they measured it over a time course.
So they did it like one hour later, 24 hours later, 96 hours later.
And what they found was that there was less tissue damage.
Same thing was sort of shown for kayakers that were doing a four-hour boat kayaking ride, which is pretty long.
Those kayakers that did cryotherapy the day before they did this four-hour kayaking event were able to do the kayaking event the next day better.
So something about doing the cryotherapy before doing the kayaking, they were able to perform better the next day when they were going to do another four-hour kayaking event.
So doing it before somehow or another activates these anti-inflammatory cytokines and then that mitigates the effect of exercise-induced pro-inflammatory cytokines?
So studies have been shown that if you do it right after training, it helped mitigate.
And also if you did it before, it helped mitigate.
But another study that you mentioned showed that men that were doing these sort of squats and they were doing leg presses and other leg exercises, when they did cold water immersion immediately after, it actually prevented muscle hypertrophy or hyperfetory, I think it's called.
And I think in that case, you know, if you're just doing your everyday, you know, average gym workout, like the minimal effective dose, probably not a good idea to do the cold shock right after, cold water immersion or cryotherapy right after that, because the amount of pro-inflammatory things, the amount of stressful things that your body's producing isn't so out of control.
And you need to make those to have the anti-inflammatory response.
So I really think there's a spectrum in terms of, are you an athlete that's doing the minimal effective dose?
Are you just going there and doing a few exercises to get a benefit?
Or are you really, really pushing it?
Are you really training hard?
Are you one of those People that's like a professional athlete.
They are training really hard.
They are pushing it to the next level.
And those are the ones that are really subject to having this overactive immune response because they're training super, super hard.
So I think that when you have a study come out that says Doing a cold water immersion after this workout, you know, mitigates muscle hyperfetri.
You can't just go, oh, all athletes should never do, you know, any sort of cold shock after working out because look, it stops muscle growth.
That's not really, it's not the case, because you have to look at the context, you have to look at the athlete, the type of exercise you're doing.
There's so many factors, you know.
It's kind of like when these studies come out saying, if you take beta-carotene, it's going to cause cancer.
Well, all the studies that were done with beta-carotene that caused cancer were done in smokers, and we know That smokers, if you take beta carotene, they've got this very oxidative environment in their lung that chops the beta carotene up into bad things that can damage your DNA and lead to mutations that cause cancer.
The same amount of beta carotene given to people that don't smoke, guess what?
It doesn't do that.
So you can't just say, taking beta carotene caused cancer.
You have to look at the context, and you have to understand what's going on.
So I think...
That's my take on the cold and cold shock, whether that's cryotherapy or cold water immersion, and how it affects muscle recovery, how it affects performance, and even muscle growth or regrowth.
But the other thing is that there are other benefits to doing cryotherapy and to doing cold shock in general.
So the most consistent and robust effect, and it doesn't matter if it's cold water immersion.
In fact, a study has shown comparing cold water immersion where you get up to your shoulders and you just do it for like 20 seconds.
Or cryotherapy, so two minutes at like a negative 166 degrees Fahrenheit.
You release norepinephrine both in your brain and in your body.
And you release it like two to three fold.
Like it's very very robust.
And this happens every time.
So like you know studies have shown that even after 12 weeks of doing this.
The 12th week, you're still bursting out just as much norepinephrine as you did the first time you did it.
So there's no attenuation of this response.
And this is super, super cool because norepinephrine in the brain is actually, it's a neurotransmitter and it's associated with Prolonged focus, attention, vigilance.
It's also associated with energy, like this feeling of energy and positive mood.
It makes people feel better.
You know, when you pharmacologically deplete norepinephrine from people, they become depressed.
Cognitive dysfunction happens.
They also become anxious and they feel lethargic.
So norepinephrine in the brain is acting as a neurotransmitter, but it's also acting as a signaling molecule.
In the brain, where it's been shown to decrease inflammation.
It's been shown to decrease the induction of these pro-inflammatory cytokines that are basically...
Inflammation is like your immune system that is overactive, and it's making all these damaging products that are causing damage to your tissues, to your cells.
It's kind of like setting off a nuclear bomb to kill a cockroach, where your immune system is like...
Right?
And they're like, whoa, there's lots of damage going on here.
So norepinephrine is able to stop that from happening in the brain.
In the body, it's acting as a hormone.
It causes vasoconstriction acutely.
And this Is part of a response mechanism to conserve energy, heat.
So you're basically conserving it.
And it also is involved in analgesic effects.
So it's able to reduce pain.
And norepinephrine is actually injected into people that have back problems, their spine, and it totally alleviates their pain.
A variety of different mechanisms, partly through the opioid pathway and things like that.
But I think that's...
Why cryotherapy has been shown to help with pain, partly why.
There's other things going on.
You also are slowing like nerve ending, you know, like the conduction of nerves, you know, at the end of nerves.
So like the pain's responses are slowed.
That's also happening.
The norepinephrine response in itself is really cool because it's doing really good things in the brain and it's also got a positive effect in the body of being anti-inflammatory.
So I think that in itself is really cool and if you think about it in the context of professional athletes that are subject to severe injury and damage like brain trauma, UFC fighters that are getting blows to the head, NFL players, You're talking about using cryotherapy to mitigate some of that damage.
Part of getting a blow to the head activates the immune system, and we talked about this in great detail last time I was here.
So being able to slow that inflammatory process immediately after it happens has very positive effects on people that have had trauma to the head.
And I think that in and of itself, aside from the recovery aspect, is very interesting and important.
In fact, it's hypothermia, which is cooling down the body, is used to treat traumatic brain injury in clinical settings.
So it's something that's used, and it's also used to treat ischemic stroke, things like that.
And I think part of that's through this norepinephrine response that's very, very robust.
So you're talking about, like, decreasing damage that's, you know, causing more brain aging.
Maybe it's that, but I feel happy when I get out of there.
I feel happy and I feel energetic.
The way I always describe it, I feel like I could jump over cars.
You just feel like...
Like once your body recovers from that initial burst, whatever your body is producing to deal with the effects of that insane cold gives you this amazing feeling of euphoria when you're out of it.
Yeah, I mean, that makes perfect sense from the study that I read.
And, you know, norepinephrine reuptake inhibitors, which prevent norepinephrine, so you release norepinephrine from your neurons, and they then, you know, go into the synapse, and then they bind on another neuron, and that's how they have function.
Well, norepinephrine reuptake inhibitors prevent it from being metabolized, so it sits around longer in the synapse and can do its function.
It's used to treat ADHD, to treat depression.
You know, of course, I think there's a lot of...
There are possible side effects with that, because when you're constantly allowing norepinephrine to sit around in the synapses, there's biological responses to that, you know, one of those being the receptors, you start to make less of them.
But, you know, that's a different topic.
But it is interesting that it's used to treat depression.
Like I said, people that are pharmacologically depleted of it become depressed.
And studies have shown, at least, they're not randomized controlled trials, but they're Their decent enough trials have shown that cryotherapy has been used successfully to treat depression and anxiety, I think partially because of this norepinephrine effect.
So the norepinephrine that you're talking about, the negative effects of it, is this from taking an external source of it or from your body producing it endogenously?
So you're basically, it's kind of like a serotonin reuptake inhibitor, same concept.
So, you know, they're basically stopping your body from metabolize.
So usually there's a certain half-life, which means norepinephrine is around in your neurons for a certain amount of time.
And then it's metabolized, and then you release more epinephrine.
So there's a cycle.
But if you stop that from happening, the norepinephrine sits around longer in the synapses, and it's there doing its function for a longer period of time.
And so it makes people feel better.
But when you're doing something like cryotherapy, you don't have to pharmacologically inhibit the pathway to prevent it from being reuptake.
Instead, you're just Releasing two to three fold more of it than you normally would it's still gonna get metabolized normally so you don't have all these crazy responses Biological responses feedback loops that happen and you feel really I think you would feel really good and Feel energized feel happy and also have you noticed anything with focus and attention?
Um, I don't know so I do so many Eric and I were having this conversation earlier It's hard to tell when you do so many different things What's the thing that's having the effect?
Right.
I'm some sort of a performance-enhancing junkie in a lot of ways.
I'm constantly taking, oh, you know, I heard circuminum, that's what you gotta take.
Okay, turmeric, get in on it.
Alright, fish oil, I'm in.
You know, like, my body's like, fuck, dude.
You know, like, between that and the healthy foods and those nutrients, I don't have a problem with focus.
The only time I have a problem with focus is when I'm tired.
And that's usually just a lack of sleep issue or too much exercise issue.
But I definitely feel elevated when I do it on a regular basis.
One, when you were talking about the studies on the kayakers and all these different people and they did cryotherapy, were they doing cold water immersion or were they doing the dry cryotherapy?
Now when they say whole body cryotherapy, there's two different types of that as well.
There's from the neck down and then there's the kind that covers your entire head.
You don't see that as much.
You see a lot of it where you step into this thing and it kind of like, it just sort of closes like, almost like saloon doors and from your head up You're exposed you're you're in normal air and you You know the the cold air the nitrogen is all below you from the neck down the ones that they have like cryo health care And I know the one that Chad Mendez is a UFC fighter.
He uses one in Sacramento You step into a room And you close the door and your whole body's, your head, everything.
And apparently the effect of having your head involved makes a big difference.
It makes a big difference not just to mitigate the effects of training and getting hit in the head and all sorts of different inflammatory responses from that.
But also that your body, because everything is in that cold, your body is like, this isn't a matter of like dipping our toes in the river.
We just got dropped off at the top of the world and we're going to fucking freeze to death.
So we got to figure out a way to do something about this right away.
I would like to see some studies done on what the hell is actually going on.
Like what is the difference between having it from the neck up or having it from your entire body?
And if there are studies out there, I'd love to read them.
Well, usually whole body, in the scientific literature, there's whole body hyperthermia, there's whole body hypothermia.
So the whole body hyperthermia is when they like put your whole body in like a sauna You know or if it's a mouse they put you in so you do the whole body So typically it's like everything including the head, but if it's super rare, I don't know I mean that that wasn't distinguished and in those studies.
Because when you're doing the heat, you're causing basal diolation, you're increasing plasma, blood flow to the heart, and then all of a sudden when you're doing norepinephrine, you're constricting.
You know, the other thing people use it for, this cold shocking, is for, because the norepinephrine also ramps up metabolism, and it does that because it's trying to, it activates a pathway that inside of your cells, where you're making energy, the They're tricking these mitochondria, which are the sites of the energy production, into thinking that...
So typically there's an electrochemical gradient that's made, and that's how your cell senses, okay, I'm making energy.
Well, norepinephrine activates something that uncouples that.
It's called uncoupling protein 1, UCP1. And what happens is it tricks your mitochondria into thinking it's not making any energy and it's like, oh my god, I've got to make energy.
So it ramps up metabolism.
And the reason that happens is because you basically want to make more heat when you're cold.
So that's kind of like the body's way of doing it.
And so people actually lose weight.
When they do this cold shock frequently because they're able to basically trick the body into thinking it's not making energy by uncoupling this whole metabolism process, and then the body speeds up metabolism to end up burning fat more.
Yeah, it's probably, you know, cryotherapy, doing it for two minutes, I mean, you get cold and there's obviously it's been shown nor epinephrine gets activated, all those things happen.
But in order to really like have this effect that I'm talking about, you basically have to like shiver and then you don't shiver.
So it's, you have to really like, I think, have a prolonged period of being cold where you're like sitting in cold water for 20 minutes.
Yeah, I would think that the cryotherapy, you know, like I've seen studies where they've looked at cryotherapy, the effects of cryotherapy on rectal temperature, on muscle temperature.
Well, I mean, rectal temperature is indicative of core body temperature, but you really only drop a couple degrees.
Because they say that being in the cold, like in cold weather, like they say if you want to lose weight, just wearing a light jacket in cold weather makes you lose weight.
You know, there was a really interesting study that just came out a couple weeks ago where they looked at the rates of aging in young adults.
So they looked at different time points.
There was a whole, I think it was like over a thousand people.
And the study started when they were like 26 years old.
And they measured like 18 different biomarkers of aging.
So they looked at like DNA health.
They looked at telomere length.
So telomeres are those caps on the end of your chromosomes that protect them from damage.
They're a marker for aging.
They looked at HDL cholesterol.
They looked at C-reactive protein, which is an inflammatory mediator.
They looked at 18 different things.
And they looked at these people that were 26 years old, and then they did it again when they were 32, and then they did it again when they were 38. And what they found was that even though these people were all the same chronological age, their cells looked Very, very, very different.
People age at different rates.
Some people, if you looked on the cellular level, they look 10 years older and some people look 10 years younger than their chronological age.
And I was looking at some of these graphs of people and you can see some people started out Like, they started out bad, where they looked old, and then they started getting better.
You know, they probably started changing their diet, their lifestyle.
Other people started going worse.
Some people stayed the same.
You know, so there are lots of different variables going on here.
But I think what's really interesting—oh, and by the way, their physical appearance also correlated with not their chronological age, but their biological age, is what it's called.
So if they showed their picture to people, random people, and said, guess what age they are, they would guess their biological age, not their chronological age.
So if a person was 38, but they looked 28, the person would say, oh, they're probably 28. And if the person was 38, but they looked 48, they just looked worn and, you know, rough, then the person would guess that they were much, much older than they were.
So there was a correlation between physical appearance and the biological age.
I found this really, really interesting because I think it is strong evidence for the fact that your diet and your lifestyle play a major role in the way you age.
And that's something a lot of people...
There is a genetic component.
There is definitely a genetic component.
I was talking about this pathway FOXO3 that activates all this great stuff and you can deal with stress easier.
Those people are lucky.
My husband's one of those guys.
I'm not.
So he's got the variation of that gene that he's likely to live 2.7 times more likely to live to be 100. Whoa.
I took this opportunity to really think about how your diet and lifestyle plays a role in the way you age and what you can do to be that person that looks 10 years younger biologically versus 10 years older.
You know, and, and there are really, you know, there's, as we age, we talked about this, the damage accumulates.
And also what happens is our ability to repair the damage decreases.
So it's like, not only are you increasing the damage, but your body is like decreasing its ability to take care of it and then reaches point and it's like death, you know, it's just too much damage over, you know, overload and things start to shut down.
And I started looking at, well, what are like the major causes of death, like in the United States, for example?
If you look at the major causes of death in the United States, cardiovascular disease is number one, cancer is number two.
So most people that are dying, when they die, they die of cardiovascular disease.
And then the second most common thing they die of is cancer.
And if you think about that, and studies have actually shown for cardiovascular disease, like 80% of that is preventable by diet.
So in the context of cardiovascular disease, and this is where I started to really dive into this, you know, heart health.
A decade ago or so, we were all told, maybe it's two decades by now, I don't know, time's flying.
We were all told that, you know, to have good heart health, you need to decrease your saturated fat intake, right?
It's all cholesterol clogs up your arteries.
And when you have cholesterol clogging up your arteries, plaques form, they rupture.
When they rupture, then this causes a clot to form.
And then if the clot forms in an artery to your heart, you have a heart attack.
If it forms in an artery to your brain, you have a stroke.
And we were bled to believe this is all because of, you know, the fat we eat.
And we know now that it's much, much more complicated than that.
And in fact, that thought, like, did a lot more damage because then people started to eat something called trans fats, which, like, did so much more damage than, you know, eating regular fat.
And recently the FDA, thank God, like, banned all trans fats.
It causes your cells to become really stiff, which is what happens when you age because of damage.
So it's like aging in accelerated time.
And it causes heart disease, all sorts of problems.
I mean, it's so bad.
Back to their cause, the actual cause of it, of this cardiovascular disease, it actually, I think, comes down to gut health.
I know I talk a lot about micronutrients and the importance of vitamins and minerals, and that also plays a very important role in the way you age, and you and I have talked a lot about this.
But I kind of wanted to touch a little bit on this topic because I think it's really important since, you know, I know my parents' generation It's been really hard to de-educate them and like help have them relearn everything they thought was bad and them understand, well, everything you thought was bad is actually not bad and let me explain what actually is bad, you know, because I want them to be able to change their dietary habits and be healthy.
I think most people that are educated in health know that it's not just about cholesterol.
They know, well, it's LDL cholesterol, and it's not just LDL cholesterol.
It's small, dense particles, right?
You've heard that.
And the difference between HDL and LDL? You actually need cholesterol.
LDL, it's not actually cholesterol.
LDL is a lipoprotein that transports cholesterol.
It transports fatty acids and other things, but it's easy to think, it's easy to call LDL cholesterol because that's what people think about it.
So LDL cholesterol transports cholesterol to your cells, to your cells in your liver, to your cells in your kidney, to your cells in your muscle.
And it does that because...
Every cell in your body needs cholesterol.
It's part of the membrane of the cell, which is essential for the way the cell functions.
Anytime you damage your cell, anytime you're making a new cell, guess what?
It needs cholesterol.
You go out, you go to the gym, you work really hard, you got some damage.
You need cholesterol to repair that damage.
So LDL brings the cholesterol to your cells.
Once it gets to your cell, then something cuts it off, like a little piece of the cholesterol gets cut off, cut off the LDL, and then the LDL goes back to the liver and it's recycled.
So that's in a normal situation.
So what happens is, what HDL does is, HDL brings the cholesterol from your cells or from your arteries, if it's built up, and it just rips it off and brings it back to the liver.
So it's basically taking cholesterol away from your cells, away from your arteries.
The things that are built up in your arteries and your veins.
So it's removing that and bringing it to the liver.
So HDL is really important if you have too much of the bad type of cholesterol, which is the small dense.
And let me explain what small dense is because I'm sure most people have no clue what that means.
Like I said, when LDL cholesterol is going to your cell to repair damage, a little piece of it gets cleaved off and it's like, okay, here's a little piece of cholesterol.
Here you go.
And now the LDL that's left is smaller because it donated some of that cholesterol to your cell to repair.
So now it's smaller.
What happens is though, if you have an unhealthy gut, and we could talk about what causes that, but if you have an unhealthy gut, most of the back, so there's like over a hundred trillion bacteria in your gut.
And they're there because they're metabolizing the food you eat, making them into fatty acids and proteins, amino acids, things like that.
Well, you also have the highest concentration of immune cells in your gut.
Most people, when I ask them, where do you think you have the highest concentration of immune cells?
They're like, oh, your thymus, or in your blood, you know.
Nope, it's in your gut.
The highest concentration of immune cells are in your gut.
And the reason for that is because your gut is actually exposed to the external environment.
So every time you eat food from the environment, your gut sees it.
So if there's something pathogenic there, you need to have that immune response to make sure it's not going to take you out, right?
So there's a lot of immune cells in your gut.
Well, they're separated by what's called the gut barrier.
And when that becomes compromised, which we can talk about in a minute, what happens is your immune cells start to kill bacteria in your gut.
And this releases something that's part of the bacterial membrane called endotoxin.
Endotoxin then gets into your bloodstream.
And guess what?
It binds to LDL cholesterol.
And the reason why it binds to it is there's these docking sites on the cholesterol, the LDL cholesterol, that soak it up like a sponge.
So anytime you're inflamed, You actually increase your LDL production.
You actually make more LDL cholesterol.
Which is why it's important anytime you get a blood lipid panel done from a doctor, do it more than once.
Because if you had some stressful event the night before, something crazy, you're inflamed, you were sick, your LDL cholesterol is going to be through the roof.
It's just not going to be an accurate picture.
It's a snapshot of what's going on in your life at that time.
Yeah, like if you really were terrified, if you were terrified, yeah, it might actually, that might cause enough inflammation to do that.
So your cholesterol, the reason your body does that is because the endotoxin that's released It's very damaging.
I mean, endotoxin being released in the system, when you have enough of it, it can cause sepsis and death.
So your body has this response mechanism of soaking up that endotoxin, the cholesterol, so it doesn't damage your tissues.
It doesn't damage your organs.
The problem is that when that endotoxin binds that cholesterol, that LDL cholesterol that we just talked about that was donating a piece of cholesterol to your cell so it's smaller, it binds on the same docking sites that that LDL cholesterol uses to go back to the liver and get out of your circulation.
So then what happens is you're screwed because now that LDL cholesterol that's smaller has all this endotoxin there.
It can't go back to the liver.
It's stuck in your circulation.
And guess what?
Endotoxin is like a signal for your immune cells where it's like, hey, I'm a foreign invader.
Come attack me.
So now it's stuck in your circulation.
Your immune cells are seeing this signal of endotoxin that's stuck to cholesterol, but it's not bacteria.
It's cholesterol.
So they come and they try to Kill it, but they can't kill it because it's not a live bacteria.
It's your cholesterol with its endotoxin bound to it.
They secrete all these pro-inflammatory cytokines, which recruit more.
And then you get this beginning of a plaque or what it's called a foam cell, which is a bunch of immune cells stuck to this LDL particle.
So it's now small, dense because it's got all this stuff and it's stuck there in your circulation.
So really, if we look at the big picture of things, you know, saturated fat, which does increase LDL cholesterol, isn't such a bad thing unless you are under chronic inflammation.
You know, chronic inflammation at the level of the gut.
So what causes that?
Well, If you think about your gut and the bacterial cells that are there and the immune cells that are there and how they're being separated by this, it's really, it's called mucin.
So your gut cells secrete something called mucin and it looks like mucus.
I mean, it looks like snot.
It's like viscous and gross.
Anyone that's had like inflammatory bowel disease and they've had like problems and they can excrete it through their feces.
It's like all slimy.
That's mucin.
That's your gut barrier like coming out.
And that's not good.
So the mucin that's secreted by your gut cells is very, very important because it's separating your immune cells from your bacteria so that your immune cells aren't going crazy, causing this whole inflammatory cascade and releasing endotoxin.
But in order for your gut cells to make mucin, they require energy.
And your gut likes energy in this form of something called short chain fatty acids, which are basically generated from fermentable fibers, like vegetables, fruits, whole oats.
Sauerkraut, mushrooms have it, barley.
These fermentable fibers get fermented by what's called commensal bacteria in your gut, which are the good type of bacteria typically because they make these short chain fatty acids.
And when they make them, lactate, butyrate, propionate, acetate, those are the short chain fatty acids.
60 to 90% of that goes right to the gut epithelial cells and it It fuels them to make mucin.
So your gut cells love it when those short chain fatty acids come in because they're going to crank out more mucin and they're going to make sure that gut barrier is strong.
They're going to make sure that it's not breaking down, that your immune cells not coming in contact with bacteria.
When you're not feeding it the right thing, so if you're eating a lot of refined carbohydrates, refined sugars, what happens is there's a bunch of other bacteria in your gut that don't ferment these fibers.
They like to take the sugar in.
And they take the sugar in and they're overgrowing.
So they're basically occupying space in your gut that the commensal bacteria that usually are making the good stuff would occupy.
So it's like, well, if you have bad stuff here, that's less room for the good stuff, right?
The other thing that's happening is that there's actually, and this was shown very recently and it blew my mind, there's actually insulin resistance going on at the level of the gut.
So the more sugar you eat, Your gut cells begin to not respond to that sugar.
And so they're getting starved of energy because now they can't take the sugar up into the cell to make mucin because they're not responding.
They're not making insulin to be able to do that.
And so now your gut cells are starving.
When they're starving, they start breaking down mucin and then you start to have inflammation.
The key to good gut health is to not eat these refined carbohydrates, these refined sugars, and to try to eat more of the good fermentable types of fiber, like vegetables and fruits.
I mean, these are barley, whole oats also have it, and also mushrooms.
Mushrooms have a type of it called beta-glucans that are really, really...
The stevia we had before was like almost too strong.
This stuff is actually too weak.
But I don't know.
It's weird.
Like, I don't know how they're making this.
Like, how can it vary so much?
Because the other stevia we had, you would just take like a micro spoonful, like maybe a twentieth of a spoonful, and it was good for a cup of coffee.
Like, boom.
And anything more than that, I would tell people when they were trying it out, I'd be like, be really careful because you can fuck it up quick because it's so strong.
Yeah, so the fermentable, the gut bacteria are super interesting because you want to have a lot of these good stuff, the stuff that's making these things that are fueling your gut cells, the commensal bacteria.
A lot of those are lactobacillus.
In fact, I'm drinking kombucha right now that has, it only has like a billion or so lactobacillus bacteria.
And those generate these lactate and they feed our gut cells and they also feed other good bacteria.
But I actually have been experimenting recently with a probiotic.
And this has been shown, by the way, there's like 25 publications using this specific BSL No.
3 probiotic, which has six different strains of commensal bacteria, shows that it, you know, improves clinical symptoms of irritable bowel syndrome, colitis, fill-in-the-blank bowel problem, it improves insulin sensitivity, it also increases neurotrophic factors in the brain, brain-derived neurotrophic factor.
So I made a topical cream with a bunch of crazy stuff.
And then I orally took...
Tons of garlic and grapefruit seed extract.
And it was ginkgo biloba, not ginsegg.
It was ginkgo biloba.
I found studies where it was killing methicillin-resistant staphylococcus psoriasis, MRSA. And so I was both orally administered and topically, and this was in mice.
So I was trying to translate this to me, and it worked.
What was really interesting was the last time I had it, And it kept coming in the same place.
I put it on topically, and I was taking it orally, and literally within 24 hours, this thing came to a head, pussed out until there was this little hole that was left, and then it healed, and it never came back.
I'm not going to take an SSRI. And then he goes, well, how do you feel about taking an anticonvulsant?
Both of these have been shown to help with this type of pain in your abdomen.
And I said, I absolutely won't take any of these drugs.
I walked out of this office and I never went back.
And at that point, I think I reached a turning point in my belief in the medical system in general, where I said, wow.
You know, these people have no idea what's going on.
They're kind of just trial and error trying to figure things out.
No mention about my diet.
No mention about, are you taking enough fiber?
You know, what are you eating to make sure you're not getting, you know, this pain isn't because, you know, something's going on.
None of that at all.
And, you know, I went as far as, like, having them look, because I thought there might be a structural defect in, like, the last part of my colon.
So I had them look, you know, while I was awake.
You know, they were going in there and we were looking together.
And, you know, there was nothing there.
But, you know, the conclusion I came to, and I've treated myself through just, I've just had a really, it really forced me to have a great diet.
I upped my fiber intake to like, oh, you know, I'm taking like 45 grams, I get 45 grams of fiber a day, a lot of fiber.
And I really, I never really get this pain.
Much, unless something like I don't sleep and I'm really, really stressed and all these little factors come in, then I can kind of get a little bit of the pain.
But I mostly, like, it was bad.
It was so chronic and bad.
It was, like, every day.
And it was really interfering with my life.
You know, my life.
You know, granted, at the same time, I had taken these three rounds, and they were strong antibiotics.
I was also very stressed and I wasn't sleeping a lot because I was working just non-stop, just all those things.
So I became interested in the gut many years ago for that reason.
Personal experience, you know, where it's like when you're having pain every day, like you're not used to that and you don't know what's going on.
The pain wasn't getting worse, so I knew it wasn't like a tumor, you know, but still it was like I mean, If I were to listen to like people, authority, like MDs, I might be on SSRIs or anticonvulsants right now because I was like, oh, that works.
One of the things that struck me about these conversations that I have with you is there are so many things you need to learn.
There's so much information.
And every time we do a podcast together, everyone on Twitter says, Jesus fucking Christ, I've got to get my notebook out and start writing things down, start doing research, because it's the amount of data that you distribute in just a three-hour podcast is fucking staggering.
Now, when you think about the amount of time that the average person who's a doctor actually spends on nutrition, it is so small.
Like I have friends that are doctors, they joke about it.
It's like you don't learn anything.
You learn so little in medical school about actual nutrition and the effects.
And it seems to me that over the last few decades, It's just been that people are starting to be more and more aware of this, to the point where it was actually joked around.
I read this criticism of Bill Maher once, because Bill Maher, who says a lot of things I don't agree with, especially when it comes to vaccines and things along those lines, like, man, vaccines have stopped a lot of fucking diseases.
I mean, there's a lot of things that vaccines have really had a tremendous health impact for the positive on the human race.
But he had a really good point that people were mocking.
They were saying, how come when I go to the doctor, the doctor never asks me about my diet?
And they were saying, well, look at you, Bill.
You're thin.
You obviously look healthy.
That's one of the dumbest fucking things anybody could ever say.
That shows to me just the common ignorance that the average person has about...
The word diet.
Like, diet doesn't mean losing weight.
Diet means what are the nutrients you're taking into your system and what is going on with your body in response to those nutrients?
What are you missing?
If you don't get enough calcium, you get osteoporosis.
We know that there's significant factors when it comes to health and diet, but the average doctor doesn't.
The average doctor who's working 10, 12 hours a day dealing with the rising costs of medical insurance, of malpractice insurance, trying to pay off your student loans, like Jesus Christ, and then if you have a family, and then if you have a life, and then if you have hobbies, Where do they have the time?
It seems like you need a whole panel of experts just to figure out how to maximize and optimize the human body, just with food.
I mean, it's a huge problem in terms of the medical field.
And I think that as the people are becoming more educated, it puts pressure on the young physicians that are You know, coming up to learn more about it.
Now, you know, exercise is another thing they don't learn about.
You know, exercise is so important.
It's a very important component of health, of disease prevention.
You know, it's been shown to not only prevent cancer For example, which is the number two cause of death in the United States, but it's been shown to help treat cancer.
So people that have, for example, colon cancer and they exercise a lot, they're much less likely to have cancer recurrence.
I mean, this has been shown in mouse models where they give them tumors.
If they exercise vigorously, then they're...
Basically, they kill twice as many tumor cells as they do if they don't exercise.
And this is also very similar to what a chemotherapy drug does.
And if you look, actually most doctors that are surveyed, they don't know about these things.
They don't take an exercise.
In fact, 50% of all of the medical institutions, United States at least, they offer no curriculum.
And of the ones that do offer it, it's optional.
For a medical student that's starting their training to take.
I think that what's going to happen is eventually The older generations are going to die off, and that's kind of what happens, you know.
And then we repopulate the new field with people that are more trained, more educated.
I do see a lot of younger physicians.
In fact, a lot of them reach out to me and say that they've learned a lot from some of my videos, from listening to me on the Joe Rogan experience.
You know, so I know that there's a group of people, young physicians out there, that, you know, are interested in prevention, are interested in You know, understanding this complex interaction between nutrition and how it affects disease susceptibility, how it can, you know, help you not only optimize your performance in certain things, cognitive performance, but also can prolong your lifespan.
It's, you know, I do it because, you know, I really like getting this information, synthesizing this information and communicating it to people.
That's something I really enjoy doing.
I get feedback, you know, I do it part-time, but it takes a lot of time and I want to shift more of my focus to doing this.
But I mean, I get messages all the time from people saying that they've listened to me on the JRE or they've I've, you know, listened to my videos and they've, you know, fine-tuned their diet, their micronutrient intake, and it made a huge difference in their mental health, you know, their off-drug fill-in-the-blank, you know, their physical health is better, and it's, you know, so I think it's important, you know, for people To communicate this health information to the public, and there are people doing it, and that's one way.
And communicate it to doctors as well.
So it helps if you have someone else break it down for them, because they don't have the time.
There is an issue also where doctors don't want to admit that they don't know things, and they don't want to admit that there's a significant factor that maybe they haven't researched at all that pertains to human health.
When I had that experience with my gut, and there was just no...
Talk about nutrition at all.
And one of the major things with gut health is nutrition.
I mean, it blew my mind.
It blew my mind and I realized at that point, you know, I can either blame this guy for like not knowing or maybe people don't want to change their nutrition.
Maybe he's responding to people just wanting a pill.
I mean, that's possible.
There are a lot of people that don't want to make changes that are difficult to make.
And I don't really know what the case was, but regardless, it blew my mind.
And then at that point, I said, well, I have to do this myself.
You know, I have to figure out what's going on.
And that's kind of why I got to this sequencing my poop thing, because I've had issues in the past, and so I did sequence it.
And, you know, I would say that my, if you compare it to my husband, our gut bacteria is a little different, even though we eat the same diet, you know, we're on the same circadian schedule, things like that.
The lactic acid that's produced when you exercise is absolutely related to it.
It's the same thing, and it's actually beneficial.
Most people think of it as causing muscle soreness.
It's like, oh, I'm making too much lactic acid.
My muscles hurt.
It's not actually true.
So lactate, the reason why your gut likes it is because it's an easy source of energy.
It doesn't require energy.
So when you have glucose, when you eat carbohydrates that have glucose, you have to convert that into a form that your cells can use to make energy, and that requires energy to do that.
Well, lactate, it doesn't have to do that.
It's thermodynamically favorable, meaning it doesn't require energy to make energy.
Lactate goes right into the cell, and there's a transporter on their cell and also in your mitochondria, which is where the energy is made, where it just goes right in.
And it's a really easy, usable source of energy.
So when you exercise, and this has been shown, you make more lactate.
Now the lactic acid can form because your mitochondria are pushing out protons.
It's like a little technical, but basically they're pushing out protons and as the lactates there, it can like bind onto the lactate and form lactic acid.
But then at physiological pH, it goes back to lactate.
So it's like this back and forth deal.
But the lactate's been shown when you exercise to go into the brain.
Preferentially, your neurons actually use lactate, preferentially over glucose.
Most people don't know that.
But in your brain, so you have neurons and you have astrocytes.
And the astrocytes are supporting cells that make...
They make energy for your neurons.
They actually make lactate by using glucose.
They make lactate.
Lactate then gets shuttled to the neuron and it's a really easy source they can use for energy.
And it's actually the preferred source of energy for the brain.
And in fact, a friend of mine, he's a professor at UC Berkeley.
His name is George Brooks.
He's the guy that actually, he's an exercise physiologist and he's the guy that discovered the lactate transporter.
And figured out that basically when you're exercising this lactate that you're making, the reason you're making it is because typically when you're exercising, you're doing more work.
And that oxygen we were talking about that you usually breathe in and that's used to make energy, You're doing so much work that you don't have time for that, so the glucose that you have is being used in another way, and it's making energy quicker, but it also makes lactate as a byproduct.
And so that's why when you're exercising, that happens.
Our immune cells, our T cells, they're always making lactate.
The lactate that they made in the circulation, it goes to the muscle, it goes to the heart, it goes to the brain, and it's used as a source of energy.
Like I said, it's very easy to use, so it's great.
And actually, it's being used to treat TBI. My friend George Brooks is now collaborating with someone at UCLA. They're working with...
Mostly TBI from gunshot wounds, guys that are coming in from fights, gang fights, things like that.
They've got a TBI from a gunshot wound.
Well, they're finding that if they immediately administer lactate through their veins, so intravenously, they're able to then, lactate can go, as long as their blood-brain barrier is intact somewhat.
You have to be able to Have oxygen getting to your brain in order to do this.
But the lactate dramatically improves their healing.
And that's for a couple of reasons.
One is because when you get a TBI, your astrocytes, which usually make it for your neurons, exercise also does this, they get damaged.
And they're not, for some reason, and no one knows why, we haven't figured out why yet, they stop making the lactate.
They're damaged and they're trying to repair all this other stuff.
So then the neurons start to have to use glucose, which means they have to work harder to use glucose to turn it into energy.
Well, lactate is a lot easier for them to use.
And so one, that's one thing that's good.
Two is that glucose can then be used to make precursors for glutathione.
So glucose can be shunted into this other pathway where it can then make precursors for glutathione, which is actually the strongest antioxidant in the brain.
So under the sources of TBI, and this has been shown, when the lactate's administered, more of that glucose is then used to make glutathione.
They're repairing this damage, and so the neurons are getting this source of energy that's more easily used.
So the lactate, when you're exercising, is actually doing a lot of good.
And it's been, like, radio-labeled, where they're able to follow it and show that people, when they exercise, it goes right into the brain.
And what's really interesting is that I've made this connection, and I'm not saying this is true, but Parkinson's patients, people with Parkinson's disease.
So Parkinson's is a disease where you're...
The dopaminergic neurons in your substantia niagra and they're dying.
And so you're not making enough dopamine.
This affects motor control.
Well, if they're forced to exercise really hard, like if you have a two person bike and they're forced to like keep up.
So it's not like you allow them to choose how hard they exercise.
They're actually forced to do it hard.
It improves their symptoms.
So their motor control gets better.
They're walking.
So their gait, the way they walk improves.
And another study came out in flies that were genetically engineered to get kind of like a Parkinson's disease where they have this screwed up stuff going on in their neurons that's very similar to Parkinson's.
When they administered them, L-lactate, it actually improved all this other, you know, the cells weren't dying, so it improved all this Energetic metabolism, things like that.
And so I'm wondering if part of the exercise that benefits the Parkinson's patients has to do with the lactate that you're producing, which gets across the blood-brain barrier, gets into the brain, and then is an easily usable source of energy for the substantial Niagara neurons.
Well, lactic acid can cause some of the muscle soreness, but it's also used to repair the damage because the lactic goes into the muscle inside the cell and is used for energy.
And there is other damage that's going on from cytokines, and there's lots of things.
Compression is a type of stress, which I think there are different physiological mechanisms that are responding to that, that probably are anti-inflammatory, but I know nothing about that, and so I'm just going to shut up.
Okay, why don't you go to the website and see if the website has...
It's fucking expensive.
Damn.
It's two grand.
Fifteen hundred bucks?
Go to the website and see if there's...
Two things that I wanted to get back to.
One thing is the second of the two things, of the first time I said two things, which was the exercise when those guys did exercise and then did cold water immersion.
How do we know what level of stress and how hard they were exercising?
Well, I mean, I think you have to look at the types of exercise they were doing, and then everyone's different.
I mean, I've seen people at the gym that they're slow.
I mean, they take forever to do a set, and they don't look like they're pushing it.
So the fact that they completed a set, I think everyone's different, right?
It's hard to tell how...
I think a really good way to do the study...
Would actually be to measure a blood biomarker like IL-1 beta or TNF alpha, which are both pro-inflammatory cytokines.
Measure the level of that that's released immediately after exercise.
So people that are really, really pushing it, like competitively, competitive trainers, athletes, they're going to have a really, really high level of that.
Like, extremely high, like off the charts, versus someone who is not pushing it as hard.
So I think that would be one way to, at least in a study, when you're designing this trial, like, so you can know, okay, well, this is the amount of, you know, inflammation, this is the amount of, and you can measure other things as well, other biomarkers, of stress that's going on in this person that's doing training.
And I think most people know.
And then after that, okay, well, then after you measure that amount, Then you do the cold therapy and then you measure biomarkers later, like anti-inflammatory and things like that.
I assumed, based on the conflicting literature, if you look at these people that were doing the hill training, and I guess it's more endurance training, but you can work out hard by doing resistance training.
They were doing leg presses and some kind of squat jumps where you...
I don't know what that is.
And I think there was something else they were doing.
But I think there's a spectrum.
I mean, there's a spectrum of athletes, of how people train.
I mean, some people train really, really, really hard.
And those people do...
We produce a lot of pro-inflammatory cytokines that spin out of control and start to not only do it have a hormetic effect where it's like, okay, this bad stuff is now signaling to turn on all this good stuff, which is great.
That's part of recovery and that's also part of growing new muscles.
So producing these damaging products activates mitochondria.
You grow more mitochondria.
And that's, you know, plays a role in things like building more muscle.
But if you have too much of that stress, it's all about the dose, then you start to have damage where the pro-stress stuff is going a little out of control.
And this is the case with people that are really, really overtraining.
And it's the case when you're injured, or like I said, in the case where you're actually getting traumatic injury, whether that's like a blow to the body or the head or...
With athletes it's a big issue trying to figure out when they are overtraining, and with wrestlers especially, they're almost chronically overtrained, especially amateur wrestlers.
One of the things that wrestlers develop is the ability to push through fatigue, It's a huge issue.
And it also creates incredible mental toughness.
I've found that amateur wrestlers are amongst the toughest, as a whole, the toughest groups of athletes that compete in mixed martial arts.
And I think one of the reasons is they're used to being really uncomfortable.
And they're used to training on a regular basis, like, way past their limits.
Like, I remember when I wrestled, I wrestled in high school, which is nothing in comparison to what they have to do in college, and especially what they have to do in, like, Olympic level.
Like, the amount of training and the brutal preparation that's involved is, if you haven't experienced it, you really don't know.
But a big factor is that these guys are overtrained all the time.
How does one know whether or not they're overtrained or whether or not you just have to keep pushing?
And push through like whatever level of fatigue and your body will eventually respond to it.
Yeah, I mean, I think that an exercise physiologist would probably be able to answer that much better than me.
But just my insights on it would be, I think, you know, measuring markers of muscle damage so your muscles release things when they start to be damaged.
So measuring these biomarkers of that like immediately after the training is a way to quantitate, at least in terms of like muscle damage, you can you can quantitate some of these things that are released when the muscles being broken down and damaged by the by the immune system.
I think that would be one way to see to actually quantitatively go, OK, look, this is what's going on after this type of workout.
You're actually causing more damage, you know, so, you know, that that would be my guess.
but I don't really know.
I'm sure people are using different things that they biomark to measure if they're overtraining or not.
With UFC athletes, there's very few people doing any kind of measuring of anything.
They're just training hard.
I mean, that's what they're doing.
It's very caveman-like in a way.
It's very old school.
in a lot of ways and I always wonder how much that mental toughness is actually them tripping over their own feet getting in the way of themselves actually recovering and would they be better off in some cases doing less and also does your your threshold does it build up over time with harder working out do you get like a higher capacity for work because you know as you get in better shape you can do more Yes.
And do you get your body to a level where it can just physically respond better to training, recover better training, do more, and then is there a boundary that you cross where that's no longer the case and now you're doing damage?
And it has been shown that the more you train or the more stress you do induce on your body because you're activating a lot of those hormetic signaling pathways and a lot of those have to do with heat shock proteins.
Those get activated.
Those protect from muscles from getting damaged.
They protect from a lot of types of damage.
The more you train, and they've shown this in athletes, the more trained athletes, the more highly activated this is all the time in the person.
And when they have this activated, they can actually endure more stress, including injury.
And that's been shown even with heat training.
So if you like to, in addition to your workout, you also use the sauna to activate these heat shock proteins.
Then you can endure more stress the next time.
That's absolutely true.
Now the threshold into, okay, at what point then do we cross over into damage again?
Well, that happens when you're doing too much of the stress and then something else stressful happens again.
So the stress plus the stress equals death, cell death, muscle cells or what have you.
And I think it depends on the person in order to determine that threshold.
You know, it depends on how much they've trained, how much they've already built up those stress response mechanisms like heat shock proteins and other things that are activated from exercise.
And also, you know, exercise causes you to build more mitochondria.
So, you know, more trained athletes can endure more because they basically can make more energy.
And so there's all these things happening.
But I do absolutely think that that has been shown and that the more stress that you do endure, the Steve Maxwell, who's a good friend of mine, is also a really well-respected personal trainer, physical trainer.
He says measuring your heart rate is a big indicator.
That if you measure your heart rate every morning, your waking heart rate as you wake up, when it starts going up, when your heart rate is up 5 to 10 beats per minute in the morning, it's more than likely that you're overtrained.
And he advocates not training at all when that happens.
Whereas, you know, a lot of coaches were like, come on, don't be a bitch.
Like, get up.
You gotta work out.
You know, you gotta be tough.
You gotta be mentally tough.
He's like, that's nonsense.
You can't do that.
If your heart rate is 10 beats above the normal resting heart rate, it means there's an issue.
And if you break your body down more, you're gonna get sick, or you're gonna get injured, or something's gonna break.
I mean, I have checked my heart rate, but I don't do it like when I wake up in the morning.
But I do notice that I will be more susceptible to getting sick.
Like if I really, really train, like push it really hard with my workout, like just over the top, I will end up getting sick.
I usually don't get sick a lot.
Once a year, maybe.
Not even once a year.
It doesn't hit me very often.
But if I really, really work out in the gym and then I'm stressed for work or something else, it's like, boom, those things, too, push me into the sickness.
I mean, that makes perfect sense because when your gut health is poor and you have this chronic inflammation, then all the energy that you're generating, we've talked about this before, it's like getting triaged into resolving that inflammation.
Well, guess what?
Your immune cells, They sacrifice things, and they are basically not getting all the energy they need to make sure they're going to fight off this infection because this other infection over here, this chronic inflammation, well, that's more important.
That was there before, and that's going on, and it's not stopping.
So I think that gut health and the immune system, there's a very intimate connection between Your gut health and your overall health, your heart health, you know, your immune health, just everything.
I think the gut health is indicative of your health status and brain function, as you mentioned.
I mean that, it really blows my mind and there's been just study after study coming out showing that gut health is linked to depression, anxiety.
You know, I don't get a lot of flare-ups, you know, when I'm traveling and I don't get to eat.
I drink this smoothie every single day that's like got tons of fiber because it's got vegetables and Even when you're on the road, do you bring it with you?
I don't.
And so that's when my gut's more susceptible.
But I've noticed that I'm a little more resilient now.
And the BSL No.
3, I think it has helped me become more resilient because it's increased the amount of the good things that are helping my gut cells.
And my gut cells have been damaged.
And also when they're...
When they're prone to activation easily, then the pain stuff happens and there's lots of neurons in your gut, you know, so that you're basically just hyperactive and the pain signals start to get activated and it's just a big mess.
But I have noticed that it has helped my gut become more resilient.
I found out about probiotics through jiu-jitsu because a lot of people in jiu-jitsu, they get all sorts of weird skin conditions like ringworm is a big one, staph is a big one, and I had both of those.
I had staph twice, and I didn't get MSO. MRSA. MRSA. I didn't get MRSA, but I did get regular staph, and I took some ungodly antibiotic that made me a zombie.
I felt so dumb.
It was weird.
It had a weird effect on my brain.
I took it, and I remember I was out to dinner with some friends, and I was telling them that it's on this medication for staph.
And I feel like I'm so out of it.
I'm drained.
I feel like I'm a half full glass and my brain is just not firing right.
So when you're taking antibiotics, you're wiping out a lot of your gut bacteria, or microbiome as it's called.
You're wiping out the bad stuff, you're wiping out the good stuff, you're wiping out lots of things.
And what's really interesting is that there is this connection between the gut and the brain and between the bacteria in your gut and the brain.
It's so interesting to me that there's some studies that have shown in mice, when you take a mouse that's, for example, anxious, take the gut bacteria, like a poop, and you do a fecal transplant, and you transplant it into a mouse that's not anxious, the mouse becomes anxious, and vice versa.
I think, you know, it's been shown in other ways as well.
Timid versus not timid.
And this has been shown in people.
So, I mean, what's going on there, right?
These mice have different gut bacteria and you're taking one from this mouse and transplanting another and all of a sudden it starts to become more anxious and things like that.
And the one that's not anxious, you transplant that into it and that usually is anxious.
You transplant the not anxious gut bacteria and it becomes not anxious.
There's a few things going on here and people actually there's been there's been clinical trials where people have supplemented with various strains of probiotics so like for example there was a trial where people took lactobacillus casey and they took it for some amount of time I don't remember but they became less depressed And also had to rely less on if they were taking some sort of, you know, drug to help with the depression, stopped having to take it.
And then another study showed that people that were anxious that supplemented with another type of lactobacillus called lactobacillus rhaminusis.
They became less anxious after taking it for some amount of time.
And so, you know, we really don't know why that is, but there's some speculation.
You know, one is that, you know, these types of bacteria that are producing, you know, lactate in your gut.
Well, lactobacillus rhaminusis also produces a neurotransmitter in the gut called GABA, which is an inhibitory neurotransmitter.
So, yeah, it's not supposed to cross over the blood-brain barrier, as far as I know.
Maybe there's some studies showing that it can, but I don't think it can.
As far as I've read, it's not very good at crossing over the blood-brain barrier.
But, in the gut, it actually inhibits the production of inflammatory cytokines, all this stuff we've been talking about.
And that would have an effect because inflammation, inflammatory cytokines, cross over the blood-brain barrier and they stop serotonin from being released.
And the other thing is there's a direct line from the gut to the brain.
It's called the vagal nerve.
And we're really starting to scratch the surface on understanding how this works.
We don't know.
When I say we, I mean scientists.
I'm not actually doing this research.
I should clarify that.
But scientists are starting to scratch the surface that we're trying to understand.
But literally, it's a line that goes to the brainstem and it extends into the gut.
And there's some kind of connection and communication going on there where the bugs in the gut are sending signals to the brain via this vagal nerve.
We don't know exactly how it works, but it's doing it.
And that's another possible way that certain gut bugs, which are producing these neurotransmitters, may be affecting brain function.
So I think there's two ways.
One is the inflammation, where they're basically lowering the production of these bad things that cross over the brain and can cause all sorts of problems by decreasing serotonin.
And two is they're communicating with this vagal nerve.
Yeah, there was some study that found neurons in the human heart.
They were trying to make some sort of a correlation between the actual heart.
Here, is the heart overlooked?
There's a TED talk on it.
Is the heart overlooked when it comes to intelligence?
The center of the nervous system of the brain has been popularly defined as a fundamental core of intellectual activity, yet in biochemistry class, bioelectricity class, bioelectricity class?
With Professor Nina Tandon, we learned about recent research suggesting that the information processing in the body may in fact be more distributed.
For example, there are increasing evidence suggesting that the, oh boy, that's a big word, cardio-electromagnetic field can actually affect human beings in close proximity.
These signals are stronger in amplitude when in direct contact, but are still detectable up to several feet away from the source.
But they're saying a certain flavor of misconception that occurs when a cultural belief intersects with a scientific factoid that superficially seems to support the belief.
A powerful meme emerged to the effect of science now provides what we have known, believed all along.
Gurus latch onto this idea to provide apparent credibility to their mysticism.
The media eats it up.
One such meme has been around for a while that the heart contains brain cells and therefore has a mind of its own, at least part of the human mind.
This is something probably to look into that might be too complicated to read off of this, but what I have understood, what I have read, something about neurons, and it's talking about neurons, it says not all neurons contribute directly to the mind, but they are saying that there are neurons in the human heart.
Well, I mean, neurons making certain, you know, neurotransmitter, depending on if they're in the gut or where they're at, you know, that does affect the brain, you know, either, you know, through an indirect or if it's the gut, a direct mechanism through the vagal nerve.
But these indirect mechanisms, just by, like I said, the inflammatory cytokines that are produced, I mean, that has an indirect effect on the brain.
So...
It's, you know, recently we found the brain is connected to the immune system.
Like, literally, the lymphatic system, you know, is connected to the brain.
And that's like something that was never, it was thought to never exist.
A second brain in the heart is now much more than a hypothesis.
Prominent medical expert Dr. Maurice Renard and others have discovered that recipients of heart transplants are inheriting donors' memories and consequently report huge changes in their taste, their personality, and most extraordinarily their emotional memories.
I don't know if that's true or not, but that's so anecdotal.
And also you're dealing with the massive traumatic incident of having your chest ripped open with a fucking double rake machine and they operating your fucking heart.
But I've been very interested in the benefits of meditation.
And so the flotation was an interesting experience because I felt like it was definitely easier to think about, you know, whatever I was thinking about at the time, which is...
I tend to analyze my intents and things like why I behave the way I behave and I start to get into this whole analytical breakdown where I try to think about why I do things and then it helps affect my future decisions, it helps me understand other people, things like that.
You know, there's a lot of brain benefits to meditation that are known.
I mean, it's been shown to slow cognitive aging.
You know, there's one study where they looked at, like, 50-year-old brains of people that have meditated for some years, and they looked like a 25-year-old brain.
So, I mean, you might say, well, they're probably doing other things as well, and a follow-up study showed that if you just take normal people after eight weeks of, like, making them do this mindful type of meditation, they increase the volume of Brain matter in five different regions of the brain So, you know, meditation is affecting the brain.
And, you know, how it's doing that, there's a variety of possibilities.
But something that I found very interesting was that it also affects the aging process in general, not just brain aging.
So meditation's actually been shown to prevent the shortening of telomeres, which is super interesting, because you're talking about slowing aging in general.
And the way it does that is by activating the enzyme telomerase, which usually is not active in most of our cells.
And meditation is able to activate that enzyme.
So telomeres, the reason telomeres shorten each year, each day, is because every time you make a new cell, Your cell has to, the telomere is, it's got DNA, you know, just like anything else in your body.
When your cell is replicating everything in the cell, the whole genome, it has to replicate the DNA of the telomere.
Well, there's like this structural defect in the way the DNA is that the machinery that replicates it, it like can't get to this little piece at the very end.
So the cell machinery goes, okay, well, I've replicated it this far.
I can't do the rest.
And so it's like, screw it.
So this little piece of telomere DNA doesn't get replicated.
So the next cell has a telomere that's just a little bit shorter.
And this keeps happening every time your cells divide and replicate.
So eventually, you know, decades later, you have really, really short telomeres.
And then the cell can either undergo cell death or it can become senescent, which means it's basically...
Not dead, but it's sitting around and it's secreting all this bad stuff that damages other cells.
So, okay, so long story short, kind of, is that your telomeres are getting shorter and that's happening just in all of us.
Things that make it worse are inflammation, these, you know, things that damage our DNA that we talked about.
But you can rebuild those telomeres by activating telomerase.
And telomerase then, even though the telomere is short...
It will rebuild that piece that wasn't copied.
So it can make it longer.
That's not active in most of our cells.
It's active in our stem cells.
But meditation activates that gene that makes telomerase.
And the telomerase becomes active and it rebuilds telomeres.
Well, it also activates telomerase much more robustly than meditation does.
The thing that people are worried about is that you're talking about if you have a person that doesn't have a good lifestyle, a person that's eating a bunch of refined carbohydrates, refined sugars, they're causing all this endotoxin to be released from their gut, which is damaging all this stuff.
Those people, if you have a bunch of damage in your cell, it can lead to mutations, and the mutations eventually can cause cancer.
Well, what happens is that your cell will decide to die as a sacrifice.
It's like, no, I don't want to get cancer, so I'm just going to pop and explode and, you know, die.
And this also happens as we age and our telomeres get shorter.
But if you have something that can activate telomerase, cancer cells actually use this mechanism to overcome our inherent death signals that is like an adaptive mechanism to getting damage.
They overcome it by activating telomerase all the time.
So then they're like, no, I'm going to live forever.
My telomeres aren't going to get short.
I have all this damage in the cell and I'm just going to keep on going.
So that's why people are worried about things like TX-65, and until there's long-term studies done, it's out there.
That probably is the case where if you have someone that already has cancer, it's not a good idea to take TI-65.
But if you already have cancer, it's also not a good idea to supplement with high doses of folic acid.
It's again down to that situation, that person-to-person experience.
So if you already have cancer, you already have cells that are mutated, that are damaged, And you take something that's going to allow their telomeres to get longer, then you're going to overcome that cell death mechanism that usually is like, die.
And that's the thing that really drives me nuts when they put out these studies.
They say, vitamins don't increase your life.
They're useless.
People live just the same amount.
First of all, Optimization is what everybody's after.
What everybody wants to do is feel the best that they possibly can.
And if you say that vitamins don't make you feel better than not having vitamins, that means to me that you're not taking vitamins.
Or you're not supplementing your diet and you're not eating healthy.
If you don't think that it has an effect, that optimizing the way you eat and the things that you put into your body doesn't have an effect on the way you feel and the way your body moves through this world, I don't buy that.
It just doesn't make any sense.
And I also don't think there's been enough long-term studies on people who have been optimizing their health and nutrition, because I don't know how many people are really doing it right.
I'm barely doing it right, and I fucking focus on it a lot.
I've actually been really diving into this topic recently because when you say doing it right, to me that means we're all different and we all have a different genetic makeup.
And there are so many polymorphisms in genes that affect vitamins and minerals, for example.
I know three people already that have a gene polymorphism in the vitamin D pathway.
So they're...
Unable to convert vitamin D3 into the pre-hormone.
They don't do it very well.
So what that means is that they actually have to take higher doses of vitamin D3 than I would take to get the vitamin D3 to be converted into that precursor for vitamin D, which is a steroid hormone that's controlling so many different processes in the body.
I talk about it all the time.
If you never get your vitamin D levels tested or if you don't look at your genetic data, which we can do now, there's consumer tools available like 23andMe that allow you to spit in a tube and send it off to this company that will then sequence all these different gene polymorphisms that are common.
And from there, you can actually interpret the data by using other tools that allow you to do that.
Prometheus is one.
It's a tool that's $5 and it lets you export your 23andMe data into this.
It basically matches it against this huge database that has all these different...
Publications on different gene polymorphisms and allows you to understand what's going on.
But I think it's really important.
So these vitamin D polymorphisms are associated with higher all-cause mortality.
So people that have this form of the gene that converts vitamin D3 into the pre-hormone, That doesn't do it well.
They actually are more likely to die of all sorts of diseases with the exception of accidents sooner than people that don't have it, which to me says, and they also have much, much lower circulating levels of vitamin D. They actually need more vitamin D. Yeah, I mean, it's very, very common.
Both my mother-in-law has it, my mom, a couple of friends that I've looked at their data.
It's so common where they're not able to use folate to make the certain precursor for epigenetics, which is how genes get activated or deactivated.
And this changes in our environment.
So folate is in greens, you know, and we get it from eating green plants.
It's important to make new DNA, but it's also important, like a fork, it's important to make new DNA, so it provides precursors for that, which you need to make new cells.
It's also important to make these precursors to make epigenetic factors that Regulate and turn genes on when they're supposed to and turn genes off when they're supposed to be turned off.
And 40% of the population has one polymorphism where they're not doing it efficiently.
So I'm not making these precursors as efficiently as I could be.
My mom is much, much worse.
She's got one that she's at 10% of her efficiency.
So she's only doing this at 10% as opposed to 100%.
But there's a way around it.
You can supplement with something called methylfolate.
So it's an easy solution.
There's other things like vitamin A pathway, for example.
You know, most people take beta carotene.
Beta carotene can be converted into vitamin A, which is very important for your immune cells to work, right?
And beta carotene also does things on its own.
It's an antioxidant.
But, like, a lot of people have a variation in the gene that converts beta carotene into vitamin A where they can't do it.
So they may be low on vitamin A, and as a consequence, your immune cells aren't working well.
They may get sick a lot or something like that.
So I think finding out certain things.
And there's also interactions with dietary macronutrients as well.
I've seen a couple of people that have a polymorphism, and it's also common, in a gene that doesn't allow them to To basically metabolize saturated fat as well.
And so these people actually, when they go on like a ketogenic diet, instead of losing weight, they actually gain weight and they actually do worse.
Meaning like a diet that's high in fat and like 10% protein, very, very low carbohydrate.
But yeah, so these people have a certain variation in this gene and that...
Regulates how they're utilizing fat.
In order to optimize your diet, your lifestyle, the supplements you're taking, I think the future will also be looking at this interaction between your genes and What these genes mean and what you can do to kind of overcome this.
Well, let's say I have this vitamin D one.
Take more vitamin D. Let's say I have this one that doesn't convert beta carotene into vitamin A well.
What do I do?
Well, I make sure I get foods that are rich in vitamin A, like organ meat or Or I take a supplement.
You don't want to take too much because vitamin A can be toxic.
There's another common one in phosphatylcholine, which is what our livers make to basically secrete fatty acids and triglycerides and stuff out of the liver to be transported by cholesterol, LDL, and things like that.
People have it, they can't do that very well, and they end up getting fatty liver.
Not only that, phosphatylcholine is important for all cells and for your brain, and low levels have been associated with Alzheimer's.
It's actually a biomarker.
Low phosphatylcholine levels are associated with increased Alzheimer's disease risk.
But, you know, there's a simple solution.
You can supplement with phosphatylcholine, or you can increase your choline intake because it can be converted into phosphatylcholine.
Things like that, I think, are really Interesting to kind of look at your unique makeup and how you can optimize your micronutrient intake and your macronutrient intake based on your own genetic makeup.
And I've seen like even with my mother-in-law, she's been taking methylfolate Because she's one of those people that don't use folate very well to make those precursors for epigenetics.
And she's always had really, really high blood pressure.
Well, one of the consequences of having this gene is that homocysteine builds up in your blood vessels, and that can have an effect of increasing blood pressure.
And this is an N of 1, but it's possible that that's helped.
I mean, she's never been able to lower her blood pressure, so it's really kind of exciting for her.
I've been diving into this recently, and I also have made a free tool on my website where people can export their 23andMe data, and I'm going to allow them to look at all the genes that I've been researching and finding that are interesting in terms of gene-nutrient interactions and ways to bypass that and get around it that you can find coming very, very soon.
I think in a couple of days I'm going to be uploading that.
The precursors for that are, for example, acetyl-CoA.
Really all you need is acetyl-CoA.
So you can actually make it from having acetyl-CoA, which you can get from even sugar, carbohydrates, glucose.
Acetyl-CoA is made from those things as well.
So having acetyl-CoA Is an essential part of that and then from there you can go on and there's all these other enzymes that can make that but that's that's really how people can make it like that don't eat any fat at all.
So people who have a vegan diet where they don't eat any animal protein and they don't take in any animal food that it's still possible to have healthy cholesterol levels healthy LDL cholesterol levels you Well, I think that it's...
Travis Barker, a very famous drummer, he was in a very famous plane crash, and he was a vegan, and apparently he was having a hard time with the skin grafts, and then he got off the vegan diet to try to fix that, and it helped him.
And as long as you take in the right amount, especially like hemp hearts or quinoa or complete proteins that are in plant form, you can live a healthy life.
That's a big misconception, right?
You just need a lot of work to live a healthy life and be vegan.
The other thing I want to ask you about is acidity in the gut.
Well, you were talking about lactic acid and acidity and, what was it, certain types of bacteria that cannot live in that environment that are negative?
When people talk about, like, there's this way that people talk about cancer.
And they always say that cancer, you know, can't live in an alkaline environment.
You have to make your blood alkaline.
And I'm always like, boy, that sounds like fucking hokum.
I hear that all the time.
And I'm like, can you really affect your body that much that you make your blood alkaline or acidic?
The reason people talk about that in terms of cancer is because cancer cells are making lactic acid.
So one of the changes that occurs in a cancer cell is that it goes from using oxygen and carbohydrate or protein or fat, whatever source as energy, and that happens in your mitochondria, that coupled process of oxygen plus the food, to make energy.
Well, cancer cells They stop doing that and they just use the energy part so they don't need oxygen.
They just use glucose to make energy and that byproduct is lactic acid.
Lactate, which then can form lactic acid.
And so I think that's where people get this whole...
conception of like that acidity and because they're like, oh, well the cancer cells are making this acidic environment and so they must want to be in an acidic environment.
Really, I mean, it all comes, that's just, it's people not understanding what's really going on is what it is.
And, you know, the cancer cells are making this metabolic change for a few reasons.
One is because if you have oxygen and your mitochondria are working and using the oxygen, you're going to make those damaging byproducts that we talked about, superoxide, hydrogen peroxide, And those will kill a cancer cell.
So, you know, and that's one of the things when you actually have a cancer cell and you force it to activate its mitochondria, the cancer cell will die.
And that's, it's used.
Like there's certain chemo drugs that do that, that are used effectively to, you know, kill these cancer cells.
But, you know, it's...
The reason that they make this lactic acid has nothing to do with it can't live in an alkaline environment.
That's just people making associations.
It's because they're basically using glucose.
And that's why if you starve a cancer cell of glucose, it can also dramatically slow its progress.
And sometimes it kills it.
If it doesn't have glucose, it can't.
Can't make energy.
It still can.
I mean, it still will use its mitochondria, but when it uses its mitochondria, it's more likely to kill it.
The other thing I wanted to ask you about is hot yoga, like the effect of hot exercise, whether or not that mimics what you were talking about, about core body temperature that's going on in sauna.
The Kronk Gym is a legendary boxing gym, and Emanuel Stewart, who's one of the greatest boxing trainers of all time, used to force his fighters to train with the heat cranked way up.
So it was just unbelievably hot in there, and people would go there to work out, they'd be like, Jesus Christ.
Christ!
And he just had this real belief that there was a massive benefit of training in that sort of an environment and then pushing yourself in that really, really hot environment when you were out of there and you left, it would pay dividends.
To address your first question, and that has been shown, yes.
Training in heat has been shown to have performance enhancements, at least in the studies that I've read with endurance training.
And that's partly because there's all these mechanisms that are in play.
You're able to increase blood flow to your heart, which then your heart does less work.
You're also increasing the heat shock proteins, which then, you know, prevent all the damage, which can then, too much damage can affect your performance.
All these things are happening.
And the more you do that, so when you train in the heat, it's harder and also those things are getting activated even more.
And it's been shown that the next time you train, If it's not in the heat, then you're sweating at a lower body temperature, so your body is cooling down quicker.
Those same enhancements with the increased blood flow kick in.
You're also able to tolerate exercising harder, which generates this heat and increases your core body temperature.
So you're able to tolerate that better as well.
I think that makes sense why people in the boxing gyms would do that.
I don't know of anybody else who does that, but I would think that if that's the case, like MMA gyms, Jiu Jitsu gyms, all of them should crank the heat way up, right?
Yeah, it's also been shown, it's very interesting, it's also been shown that heat stress protects neurons from cell death, like in mice at least, where you, if you put them, if you expose them to heat stress like 24 hours before a traumatic event, where they like puncture the skull, they have much, much less cell death.
And again, it's part of that.
You're increasing all those stress response mechanisms, and they're active, and they're active for days, days, and days later.
So when the next stress comes, your body's like, boom, bring it on.
I'm ready to handle it.
Let's do this.
And so to address your Bikram yoga...
I like it as well, by the way.
They typically use, I think it's like 100 or so degrees Fahrenheit, right?
Something like that.
And they increase the humidity depending on where you're at, you know, up to like 40%.
And then you're like doing all these poses, so you're exerting yourself.
So it's absolutely hard.
And you know, your heart rate's going and you're hot.
And so all the same mechanisms are kicking in that would kick in when you're sitting in the sauna.
That's 170 degrees Fahrenheit, so it's like a dry sauna.
But whether or not they're as robust, I don't know.
No studies have compared them.
I think that there are similar benefits from it, from doing Bikram yoga or from training in heat.
I mean, runners do that all the time, bikers as well.
I mean, that's part of their training method is to train in heat.
Because it also has performance enhancements.
They're able to endure longer running periods better than if they didn't train the heat.
So I think that's definitely translatable to things like Bikram Yoga.
I just did a steam shower this morning and, you know, I, my heart rate was getting up and, you know, it wasn't quite as difficult to stay in as it is in the sauna.
Like the difficult part is your body making dynorphin.
And I've talked about this before, that dynorphin is that thing that feels terrible.
Like you were saying, it feels awful.
awful, but then when you're done, you feel really, really good.
And that's partly because dynorphin, which is the sort of counter to endorphin, it cause it signals to your brain to make more receptors, which bind to beta endorphins and to sensitize So you're also releasing beta endorphins when you exercise and when you're in heat or whatever you're doing in the day so you actually feel better.
And that's how I actually became very interested in this, Anna, is I was using it in graduate school.
I started using it and I started to notice that I felt really, really good.
Like if I used it in the morning and I went into the lab, I was just like, I felt really good.
I could handle all the stress.
I could handle people putting more work on me.
I could handle all the crap and just, you know, stuff that would really irritate me, usually.
I was more able to just deal with it.
And so that's when I became real.
I'm like, something's going on here.
And I became very interested in the brain effects and the hormonal effects with the sauna.
So I would think that would be a big benefit to people that are going through surgery maybe to repair something, like knee surgery or something along those lines?
The only caveat is, and my concern is that because it is a stress, If you already, like, are you stressing your body and then another stress, like, I don't know, surgery seems like it's pretty stressful.
Sometimes the two stresses together can be bad.
So I was talking about it protecting against, you know, cell death with traumatic brain injury.
Well, that was when it was done before, 24 hours before the traumatic injury.
If you have a traumatic brain injury and then you get into the sauna, you're going to cause more cell death.
You're going to do more damage.
So it's...
I'm a little hesitant about saying, oh yeah, just apply it to any recovery.
Possibly, it depends on the amount of damage that was done during the surgery.
Yeah, but now, you know, now this engineering technology is getting better and better.
And so that's what they've been using with the pigs that I tweeted about, where they're now able to specifically take a gene and say, okay, I want to take this gene and I want to, like...
Either turn it into another, you know, I want to put a mutation in it that either makes it not active or I want to change it to make it better, things like that.
And so we have this new system we can do that called CRISPR. The one that was used in that study actually was another one called Talon, which is very similar.
But basically what happens is that they take these proteins that are able to, like, recognize a certain sequence.
And when you have a certain gene with it, it'll recognize that sequence when you stick it into the cell.
And it'll cut out the gene and then replace it with whatever you give it.
So it replaces it with, let's say, a non-active myostatin.
So now you take a pig, for example, that has normal myostatin, and then you, you know, give it this technology that can kind of cut out the gene and then put it with a non-active.
So now you've got, you know, myostatin that's not working.
So it's like constantly inhibited, which means now these muscles are just growing like out of control.
If you do it with an adult, it's a little different because you have to get it to the right tissue.
It complicates things more.
The technology is getting better and better, but you have to give it a targeting sequence and say, okay, go to the liver.
Go to the heart, you know, go to the kidneys, like whatever organ we're talking about, and then once it goes there, then it finds that gene, like, and cuts it out, and then, you know, can replace it with whatever you give it.
I mean, this has implications for, you know, genetic disorders like sickle cell anemia, things like that, where you're like, okay, we know what the screwed up gene is, and we know what the good one is.
Let's give it the good one, send it there, cut out the screwed up one in blood cells, and then You know, give it this good one.
And that's actually being done.
In blood cells it's the easiest because you can take blood out and you can change things and then you can transplant it back in.
And they're doing this now with actually, they're genetically engineering cancer cells, I'm sorry, immune cells to have a protein that's able to recognize a cancer cell and kill it.
So they're taking people that have cancer, they're taking out their immune, well this is clinical trials, but They're going to take out their immune cells and then they're going to genetically engineer them with this new system to make a protein that they don't normally make that can recognize a cancer cell and then kill it.
They're going to transplant it back into the person and see if it works.
It's been shown to work in mice, so the next step is seeing if it works in humans.
With the myostatin thing, it's interesting.
Doing this in humans, there's going to be all sorts of FDA regulations and all that stuff that you have to get by.
So they're experimenting with in vitro fertilized embryos that failed.
So they were going to throw them out anyways, like at a stage before they were the embryo.
It's like it's a blastocyst.
And so they're taking this cell that's going to become an embryo and they were trying to change a certain gene.
And I think it was for sickle cell.
And what they found was that when they were doing this, so they were taking this blastocyst that's going to be an embryo, and they cut out the sickle cell gene and were trying to replace it with another one, they found that it caused all sorts of mutations in other genes.
So it was clearly stuff going on we don't understand.
I think, you know, things are getting better and better and as more scientists are researching this and figuring out what's going on, why it's causing, you know, these random mutations, then we'll start to have new technology and eventually it will be able to be done.
And, you know, in bacteria, what they found was that there's these certain sequences of DNA that were, like, it had a certain repetitive sequence to it, so it had a certain, like, you know, code.
But it wasn't the bacterial DNA. They found it was actually, like, DNA sequences that were similar to viral.
It was actually viral DNA. And so they were like, well, what is viral DNA doing in this bacterial sequence?
And it turns out one of the scientists had hypothesized the reason it was there was because it was a response to be able to fight off the virus.
So they had these, you know, certain sequences like a viral DNA that could then recognize a virus and then create antibodies and things against it to Fight off the viral.
But what's really interesting is that these sequences are conserved.
There's a certain protein that we all make in our cells that recognize these sequences.
And that protein is like, it's a caspase-9.
So it's basically something that's evolutionarily conserved from bacteria to viruses to humans, mice, and we all like have a certain form of it.
So I think that was kind of how it was discovered.
And what happens when this caspase recognizes it is it like cleaves, it like cuts.
So this woman at UC Berkeley, which is kind of down the street from me, she's a scientist, she thought of this brilliant way to harness that system and use it as a technology to be able to genetically engineer things with more precision.
So it used to be like, and when I did a lot of research, I mean, when I was doing a lot of research with, you know, making a mouse have a certain gene that it doesn't usually have, the way we would do it was we'd blast this, you know, mouse with virus that basically...
It brings the gene into the cell, but it goes like anywhere.
It randomly just goes into a piece of the chromosome.
So it doesn't go exactly where the gene is supposed to go.
So this technology now is able to recognize these little patterns, cut out, you know, where that gene is usually and put in a new one.
And so it's very precise as opposed to, we're going to blast the cell with this gene and we're going to give more of it and it's going to be, we don't know where it's going to be, where it's going to be incorporated into the genome.
It's just going to be there and it's So there's all sorts of other side effects that could happen.
If you're trying to study the effect of what having more of a certain gene does, you may be studying in addition to what more of that gene does, you may be also looking at it changing other things that are going on because it's being expressed in certain places it's not.
So things like that.
So it's really like a more precise way to genetically engineer things.
Well, also interesting to think what's going to happen next.
If they just developed CRISPR three years ago, what's the three year from now thing that they're going to come up with?
Because it seems like this stuff increases exponentially and that each individual discovery and innovation gives birth to all these new improvements and other new ones that weren't possible without that.
So what CRISPR gives birth to.
What comes out of that is going to be really kind of crazy.
What I see coming out soon is that we'll be able to take stem cells and then make the stem cell have a certain...
For example, I've got a form of the ApoE gene that is very, very associated with Alzheimer's.
And it's just a sequence of DNA that's a little different than someone that doesn't have this variant, but it really increases my risk for Alzheimer's.
So you take, you know, these stem cells, and then you say, I don't want that person, I want to get rid of that ApoE4, and I want to give it another sequence where it's like the ApoE3 version.
So just change the sequence of the DNA a little bit.
And then transplant it back into the person.
Or you do that with Parkinson's disease.
These people have, some of them have something called alpha-signuclein, where they're, you know, it's basically producing this out of control and it causes aggregates to form and that leads to cell death.
So then you take the stem cells and you make it so that they don't have that form and you give them the right form and then transplant it back in.
And we're now able to make stem cells from any cell, which is really, really cool.
So the fact that we can take our skin cells and basically give them the right signals, the right cytokines, the right environment to say, here, I want you to become a neuron.
I know right now you're a skin cell, but I'm going to give you all these other things that usually happen in the brain and I'm going to make you become a neuron.
So then we'll be able to take a person's own skin cell, make it into a dopaminergic neuron, for example.
Once we figure out exactly what the right cocktail is, so there's a certain environment around these cells in your brain, and that environment is what causes them to become a dopaminergic neuron, for example.
And then they're going to figure that out, and then take the skin cell, make it become a dopaminergic neuron, and then transplant it back into someone that has Parkinson's.
I got a stem cell injection recently in my shoulder from women's placenta.
I have some small tears on my labrum and a small tear on my rotator cuff.
Apparently my shoulder has been dislocated and I didn't know.
And there's been some damage.
I knew that my shoulder was it bugged me when I exercised a lot but not enough that I thought it was anything like really wrong with it until I wound up getting an MRI and there's like you got a bunch of tears in there and they were saying you might have to get shoulder surgery eventually but let's just see what we can do here and so I'd gone through a round of Regenikine, which helped a lot, reduced inflammation, made it feel a lot better.
But this stem cell shot, I just got it.
You can still see some of the bruising.
Like see here, which is actually blood not from here, but from up here where they shot it and it was fucking really painful It was a big-ass needle and they just shoved it right into the tendon and right into the the area where there's damage And they said well, let's take a look at this in six weeks We're not exactly sure what's gonna happen and we're not exactly sure.
For one, a colleague of mine that I work with at Children's Hospital in Oakland, he actually published a paper where he was the one that discovered that the placenta was a very rich source of stem cells, much, much more than like the umbilical cord.
And it's also these placental stem cells They're able to form almost every cell type in the body.
So not only can they form blood cells, hematopoietic cells, but they can form neurons.
They can form other cell types in the body, liver cells, heart muscle.
I think he published quite a few different cell types.
But this is not being used very frequently.
I mean, there are some people that are banking their placenta.
And, like, I wasn't aware.
I know there's maybe one company or two companies that are banking the placenta, but I wasn't aware of anyone that is, like, allowing you to use someone else's placenta.
I mean, that's super, super cool of me and exciting because I actually did a podcast on this where I interviewed Franz Kuyper.
And, you know, he was talking all about how he made the discovery and how, you know, how he wants to have these huge, you know, like we have blood banks where people bank their blood and so that you can like, you know, if you need blood transfusion, you find a donor that matches.
Well, he wants to have these placenta banks where, you know, people just throw the placenta out.
And, you know, that's a huge, like, source of stem cells.
So, you know, that's a big waste.
You're talking about being able to tune people up for injuries or for neurogenic diseases, for most, I mean, anything.
Well, Dr. Davidson, who's one of the doctors that works for the UFC, he had shoulder surgery and was still having some pretty significant issues after surgery.
It was just really painful, and he had bone-on-bone arthritis, and was just really sore.
Got a stem cell injection, and he said literally within less than two months he was healed.
So there's lots of techniques that are around in terms of how you preserve the placenta source.
So it's best to preserve the whole tissue.
You don't want to isolate the stem cells from the placenta and then freeze the stem cells because they're going to be more likely to die and less likely to be able to form whatever cell they need to when you thaw them.
So I think that...
At least Franz was telling me there's a certain procedure that's really important you follow.
So depending on who's doing this, what company, you know, you may find a lot of variation in terms of the efficacy of, you know, the stem cell injection from one versus another because the viability of the stem cells, you know, also, you know, what you're doing is putting the stem cell that basically is unprogrammed so it doesn't have a program yet.
What I mean by that is the program happens With the environment that it's in.
And so different cytokines that are present in your shoulder or your connective tissue are different from the environment that's in your brain.
So that certain microenvironment then gives it signals to become whatever, connective tissue or whatever it is.
So they just injected the stem cell, like the placental stem cell.
Hurts like hell, but I gotta tell you, it's hard to figure out what's going on, again, because I do so many different things between the Regenikine and this, but my shoulder feels great.
I mean, it worked out today.
No pain at all.
I did kickboxing, so I was using it a lot.
It seems to still have issues when I press, so I'm avoiding, like, Overhead pressing and bench pressing and things along those lines.
I might eventually have to get it fixed because there is a tear in the labrum and I have a feeling this tear is like years old.
One of the problems with jujitsu is that you learn to ignore joint pain.
You just learn to sort of ignore it because everything's always hurting.
Your elbows hurt, your wrists hurt, your knees hurt, everything hurts.
Because the whole goal of the art of jujitsu is to damage joints.
So you're constantly tapping or avoiding being tapped and when you're avoiding being tapped sometimes you probably really should just tap you know meaning you give up because you're you're stressing your joint like sometimes you'll get caught in what's called an Americana where your arm gets pinned down like that and then they torque it like this and it's a lot of pressure on your shoulder or Kimura which is like the other way and it's a lot of pressure on your shoulder That's probably happened to me hundreds of times.
I just don't even know how many times it's happened because I've been doing jiu-jitsu since 1996. So it's just all those years of getting yanked on.
Like, who knows what the fuck's going on in there.
But, um...
Just having those shots, just having that one shot and the Regenikine shots as well, made a big difference in the way it feels.
Yeah, so I just had a paper published last February on how important vitamin D and the marine omega-3 fatty acids EPA and DHR are in brain health and specifically in Preventing and modifying the severity of neuropsychiatric disorders like schizophrenia, ADHD, autism, and impulsive behavior.
It's talking about the role of these micronutrients in the serotonin pathway because vitamin D increases the gene or activates the gene that converts tryptophan into serotonin.
And omega-3 fatty acids, they prevent the inflammatory molecules that are made called E2-series prostaglandins, which are generated by inflammation, stress, things like that, generate those that get into the brain and they stop serotonin from being released.
And also the omega-3s affect the serotonin receptor function.
So the vitamin D and omega-3s are affecting pretty much every part of the serotonin pathway.
And the serotonin is very important for executive function and for impulsive behavior.
When they deplete people of serotonin by depleting tryptophan, So they basically suck away all their tryptophan from getting into their brain by giving them this branch chain amino acids, which out-compete tryptophan from getting into the brain.
That actually makes sense for multiple reasons, but also when you're exhausted, meaning you're kind of overstressed, you've stressed yourself a lot, you actually...
metabolized by this other pathway.
So tryptophan in your body, like when you eat protein, tryptophan, tryptophan can either get into the brain and make serotonin, or it can be converted into something that regulates the immune system.
And so when you're stressed or inflamed, the tryptophan gets sucked into that pathway and it doesn't get into the brain.
So, and then there's also studies that have shown that like when you overwork yourself, like if you're not sleeping, that affects the addictive mechanisms in the brain and addictive behavior and And I don't remember exactly how because it's been a while since I read that study.
But I do remember that not getting enough sleep, which I think would happen when you're overworking yourself as well, something's happening in the brain where you're more likely to engage in addictive type of behavior or bad behaviors, I guess.
But yeah, serotonin totally regulates the impulsive behavior.
And the thing that I was talking about in this paper was the interaction between people that have variations in genes that are related to serotonin.
For example, the serotonin transporter, which is what metabolizes serotonin after it's been released.
And people that have these variations They basically make serotonin get metabolized quicker.
So you release it, boom.
It's like before it can do its function, it's getting metabolized.
So it's like a vacuum, just getting sucked up.
And those people are prone to depression, impulsive behavior, things like that.
And my mom has that variation.
And I looked at her genes and she's very prone to impulsive behavior and depression.
And so the point that I tried to drive home in that paper Was that people that have these gene polymorphisms where their serotonin pathway isn't working as good as it could or should, those people are the most prone to vitamin D and omega-3 deficiencies because those micronutrients are important for various parts of the serotonin pathway that I just explained.
They're the people that actually need to get the vitamin D and omega-3 the most.
And in fact, it turns out that most of the time, those are the people that are most deficient as well.
So, you know, I think that people that supplement with vitamin D and omega-3 can modulate the severity of some of this impulsive behavior or Some of this depression or, you know, other things that are as a consequence of having low serotonin.
I think that tuning up your vitamin D and omega-3, and that's been shown in clinical studies, like the mechanism for why isn't really known.
And I think it's through the serotonin pathway, but kids that are taking omega-3 supplements, ranging from one gram a day to three grams a day, that have ADHD, their symptoms are improved, or depression, or schizophrenia, these things have all been shown to help with symptoms of these disorders.
And vitamin D has been shown as well.
And so I think there's a lot of overlap between these two, and I think they both would be good, both vitamin D and omega-3.
So that's, and I've gotten people that have emailed me and told me that that's helped with their depression and, you know, things like that.
And you never know, it could be a placebo effect, but there are studies showing that it does improve those functions, impulsive behavior, depression, things like that.