Essentials: Breathing for Mental & Physical Health & Performance

00:00:00.000 | Welcome to Huberman Lab Essentials, where we revisit past episodes for the most potent and

00:00:05.400 | actionable science-based tools for mental health, physical health, and performance.

00:00:09.900 | I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford

00:00:15.700 | School of Medicine. And now for my conversation with Dr. Jack Feldman.

00:00:20.100 | Thanks for joining me today. Pleasure to be here, Andrew.

00:00:22.760 | You're my go-to source for all things respiration and how the brain and breathing interact.

00:00:30.160 | You're the person I call. Why don't we start off by just talking about what's involved in generating

00:00:35.580 | breath? So on the mechanical side, which is obvious to everyone, we want to have air flow in, inhale,

00:00:43.740 | and we need to have air flow out. And the reason we need to do this is because for body metabolism,

00:00:50.960 | we need oxygen. And when oxygen is utilized through the aerobic metabolic process,

00:00:59.120 | we produce carbon dioxide. And so we have to get rid of the carbon dioxide that we produce in particular

00:01:04.720 | because the carbon dioxide affects the acid base balance of the blood, the pH. And all living cells

00:01:11.840 | are very sensitive to what the pH value is. So your body is very interested in regulating that pH.

00:01:18.000 | So how do we generate this air flow? We have to expand the lungs. And as the lungs expand,

00:01:24.720 | basically it's like a balloon that you would pull apart. The pressure inside that balloon drops,

00:01:30.320 | and air will flow into the balloon. That lowers the pressure in the air sacs called alveoli,

00:01:36.320 | and air will flow in because pressure outside the body is higher than pressure inside the body when you're

00:01:42.320 | doing this expansion, when you're inhaling. What produces that? Well, the principal muscle is the diaphragm,

00:01:49.440 | which is sitting inside the body just below the lung. And when you want to inhale,

00:01:55.040 | you basically contract the diaphragm, and it pulls it down. And as it pulls it down,

00:02:00.320 | it's inserting pressure forces on the lung. The lung wants to expand. At the same time,

00:02:05.840 | the ribcage is going to rotate up and out, and therefore expanding the cavity, the thoracic cavity.

00:02:13.920 | At the end of inspiration, under normal conditions, when you're at rest, you just relax. And it's like

00:02:20.880 | pulling on a spring. You pull down a spring, and you let go, and it relaxes. Where does that activity

00:02:26.080 | originate? The region in the brainstem, that's once again, this region sort of above the spinal cord,

00:02:33.200 | which was critical for generating this rhythm. It's called the pre-Butzinger complex. This small site,

00:02:40.320 | which contains in humans a few thousand neurons, it's located on either side and works in tandem. And

00:02:48.560 | every breath begins with neurons in this region beginning to be active. And those neurons then

00:02:58.240 | connect ultimately to these motor neurons going to the diaphragm and to the external intercostals causing

00:03:05.280 | them to be active and causing this inspiratory effort. When the neurons in the pre-Butzinger complex

00:03:11.360 | finish their burst of activity, then inspiration stops. And then you begin to exhale because of this passive

00:03:22.640 | recall recall of the lung and rib cage. Is there anything known about the activation of the

00:03:29.760 | diaphragm and the intercostal muscles between the ribs as it relates to nose versus mouth breathing?

00:03:36.000 | I don't think we fully have the answer to that. Clearly, there are differences between nasal and mouth

00:03:42.480 | breathing. At rest, the tendency is to do nasal breathing because the air flows that are necessary

00:03:52.080 | for normal breathing is easily managed by passing through the nasal cavities. However, when your

00:03:59.120 | ventilation needs to increase, like during exercise, you need to move more air. You do that through your

00:04:05.280 | mouth because the airways are much larger then and therefore you can move much more air. But at the

00:04:10.960 | level of the intercostals and the diaphragm, their contraction is almost agnostic to whether or not the

00:04:21.600 | nose and mouth are open. Maybe you could march us through the brain centers that you've discovered

00:04:29.280 | and others have worked on as well that control breathing, pre-Botzinger as well as related structures.

00:04:35.680 | So, when we discovered the pre-Botzinger, we thought that it was the primary source of all

00:04:42.240 | rhythmic respiratory movements, both inspiration and expiration. And then in a series of experiments,

00:04:50.160 | we discovered that there was a second oscillator. And that oscillator is involved in generating what

00:04:57.920 | we call active expiration. That is this active-- Like if I go, shh. Yeah. Or when you begin to

00:05:04.960 | exercise, you have to go, and actually move that air out. This group of cells, which is silent at rest,

00:05:14.240 | suddenly becomes active to drive those muscles. And it appears that it's an independent oscillator in a

00:05:21.840 | region around the facial nucleus. When this region was initially identified, we thought it was involved

00:05:29.440 | in sensing carbon dioxide. It was what we call a central chemoreceptor. That is, we want to keep

00:05:35.440 | carbon dioxide levels, particularly in the brain, at a relatively stable level because the brain is

00:05:40.880 | extraordinarily sensitive to changes in pH. If there's a big shift in carbon dioxide, there'll be

00:05:47.760 | a big shift in brain pH. And that'll throw your brain, if I can use the technical term, out of whack.

00:05:54.000 | And so you want to regulate that. And the way to regulate something in the brain is you have a sensor in

00:06:00.880 | the brain. And others basically identified that the ventral surface of the brainstem, that is the part of the

00:06:08.000 | brainstem that's on this side, was critical for that. And then we identified a structure near the

00:06:14.800 | trapezoid nucleus. It was not named in any of these neuroanatomical atlases. So we just picked the name

00:06:22.000 | out of the hat, and we called it the retrotrapezoid nucleus. If you go back in an evolutionary sense,

00:06:28.000 | and a lot of things that are hard to figure out begin to make sense when you look at the evolution of the

00:06:34.480 | nervous system, when control of facial muscles going back to more primitive creatures, because they had to

00:06:43.360 | take things in their mouth for eating. So we call that the face sort of developed. The eyes were there,

00:06:50.160 | the mouth is there. These nuclei that contained the motor neurons, a lot of the control systems for them

00:06:58.960 | developed in the immediate vicinity. So if you think about the face, there's a lot of sub nuclei around

00:07:05.840 | there that had various roles at various different times in evolution. And at one point in evolution,

00:07:13.120 | the facial muscles were probably very important in moving fluid in and out of the mouth and moving air in

00:07:20.400 | and out of the mouth. And so part of these many different sub nuclei now seems to be in mammals to

00:07:28.640 | be involved in the control of expiratory muscles. But we have to remember that mammals are very special when

00:07:36.800 | it comes to breathing because we're the only class of vertebrates that have a diaphragm. If you look at

00:07:43.280 | amphibians and reptiles, they don't have a diaphragm. And the way they breathe is not by actively inspiring and

00:07:52.320 | passively expiring. They breathe by actively expiring and passively inspiring because they don't have

00:08:00.320 | a powerful inspiratory muscle. And somewhere along the line, the diaphragm developed. The amazing thing about

00:08:09.280 | the diaphragm is that it's mechanically extremely efficient. If you look at how oxygen gets from

00:08:16.080 | outside the body into the bloodstream, the critical passage is across the membrane in the lung. It's

00:08:24.960 | called the alveolar capillary membrane. The alveolus is part of the lung and the blood runs through

00:08:33.120 | capillaries, which are the smallest tubes in the circulatory system. And at that point, oxygen can go from

00:08:40.560 | the air-filled alveolus into the blood. The key element is the surface area. The bigger the surface

00:08:48.960 | area, the more oxygen that can pass through. It's entirely a passive process. There's no magic about

00:08:55.040 | making oxygen go in. Now, how do you get a pack, a large surface area in a small chest? Well, you start

00:09:04.000 | out with one tube, which is the trachea. The trachea expands. Now, you have two tubes. Then you have four

00:09:11.120 | tubes, and it keeps branching. At some point, at the end of those branches, you put a little sphere, which

00:09:18.880 | is an alveolus. And that determines what the surface area is going to be. Now, you then have a mechanical

00:09:27.360 | problem. You have this surface area. You have to be able to pull it apart. So, imagine you have a little

00:09:33.760 | square of elastic membrane. It doesn't take a lot of force to pull it apart. But now, if you increase it

00:09:41.520 | by 50 times, you need a lot more force to pull it apart. So, amphibians who were breathing not by compressing

00:09:49.760 | the lungs and then just passively expanding it, weren't able to generate a lot of force. So,

00:09:56.000 | they have relatively few branches. So, if you look at the surface area that they pack in their lungs,

00:10:01.760 | relative to their body size, it's not very impressive. Whereas, when you get to mammals,

00:10:08.880 | the amount of branching that you have is you have four to 500 million alveoli. So, you have a membrane

00:10:17.840 | inside of you, a third the size of a tennis court, that you actually have to expand every breath.

00:10:23.840 | And you do that without exerting much of a, you don't feel it. And that's because you have this

00:10:29.360 | amazing muscle, the diaphragm, which because of its positioning, just by moving two thirds of an inch

00:10:36.720 | down, is able to expand that membrane enough to move air into the lungs. At rest, the volume of air in

00:10:44.880 | your lungs is about two and a half liters. When you take a breath, you're taking another 500 milliliters or

00:10:52.320 | half a liter. That's the size maybe a little of my fist. So, you're increasing the volume by 20%.

00:10:59.520 | But you're doing that by pulling on this 70 square meter membrane. But that's enough to bring enough fresh

00:11:07.840 | air into the lung to mix in with the air that's already there that the oxygen levels in your bloodstream

00:11:15.680 | goes from a partial pressure of oxygen, which is 40 millimeters of mercury to 100 millimeters of mercury.

00:11:25.040 | So, we have this amazing mechanical advantage by having a diaphragm.

00:11:31.680 | Do you think that our brains are larger than that of other mammals in part because of the amount of

00:11:38.400 | oxygen that we have been able to bring into our system?

00:11:41.520 | I would say a key step in the ability to develop a large brain that has a continuous demand for oxygen

00:11:50.160 | is the diaphragm. Without a diaphragm, you're an amphibian.

00:11:54.880 | You know, over the years, whether it be for yoga class or a breathwork thing or you hear online that

00:12:03.360 | we should be breathing with our diaphragm, that rather than lifting our rib cage when we breathe

00:12:08.080 | and our chest, that it is "healthier" or better somehow to have the belly expand when we inhale.

00:12:15.440 | I'm not aware of any particular studies that have really examined the direct

00:12:19.760 | health benefits of diaphragmatic versus non-diaphragmatic breathing.

00:12:24.240 | But if you don't mind commenting on anything you're aware of

00:12:29.200 | as it relates to diaphragmatic versus non-diaphragmatic breathing, that would be,

00:12:33.200 | I think, interesting to a number of people.

00:12:34.800 | In the context of things like breath practice, I'm a bit agnostic about the effects of some of the

00:12:44.160 | different patterns of breathing. Clearly, some are going to work through different mechanisms and we

00:12:50.480 | can talk about that. But at a certain level, for example, whether it's primarily diaphragm where you

00:12:56.400 | move your abdomen or not, I am agnostic about it. I think that the changes that breathing induces

00:13:05.680 | in emotion and cognition, I have different ideas about what the influence is, and I don't see that

00:13:14.400 | primarily as how which particular muscles you're choosing. But that just could be my own prejudice.

00:13:22.320 | Yes.

00:13:22.480 | Could you tell us about physiological sighs, what's known about them, what your particular interest

00:13:28.880 | in them is, and what they're good for?

00:13:31.600 | Well, it turns out we sigh about every five minutes. And I would encourage anyone who finds that to be

00:13:40.320 | an unbelievable fact is to lie down in a quiet room and just breathe normally, just relax, just let go,

00:13:50.320 | and just pay attention to your breathing, and you'll find that every couple of minutes, you're taking a deep

00:13:56.880 | breath, and you can't stop it. You know, it just happens. Now, why? Well, we have to go back to the

00:14:05.360 | lung again. The lung has these 500 million alveoli, and they're very tiny. They're 200 microns across, so

00:14:12.960 | they're really, really tiny. And you can think of them as fluid-filled. They're fluid lines, and the

00:14:19.280 | reason they're fluid lines has to do with the esoterica of the mechanics of that. It makes it a little easier

00:14:27.360 | to stretch them with this fluid line, which is called surfactant. Your alveoli have a tendency to collapse.

00:14:35.120 | There's 500 million of them. They're not collapsing at a very high rate, but it's a slow rate that's

00:14:41.440 | not trivial. And when an alveolus collapses, it no longer can receive oxygen or take carbon dioxide out.

00:14:50.400 | It's sort of taken out of the equation. Now, if you have 500 million of them and you lose 10,

00:14:55.840 | no big deal. But if they keep collapsing, you can lose a significant part of the surface area of your lung.

00:15:04.160 | Now, a normal breath is not enough to pop them open. But if you take a deep breath-

00:15:11.040 | Through nose or mouth. Okay.

00:15:12.400 | Doesn't matter. Or-

00:15:13.600 | It's just increased that lung volume because you're just pulling on the lungs.

00:15:17.600 | They'll pop open about every five minutes. And so we're doing it every five minutes in order to

00:15:26.560 | maintain the health of our lung. In the early days of mechanical ventilation, which was used to treat

00:15:33.520 | polio victims who had weakness of their respiratory muscles. They'd be put in these big steel tubes.

00:15:41.920 | And the way they would work is that the pressure outside the body would drop. That would put a

00:15:48.480 | expansion pressure on the lungs, excuse me, on the rib cage. The rib cage would expand. And then the

00:15:54.800 | lung would expand. And then the pressure would go back to normal. And the lung and rib cage would go back to

00:16:00.960 | normal. But there was a relatively high mortality rate. It was a bit of a mystery. And one solution

00:16:08.560 | was to just give bigger breaths. They gave bigger breaths and the mortality rate dropped. And it wasn't

00:16:14.000 | until I think it was the '50s where they realized that they didn't have to increase every breath to be big.

00:16:21.600 | What they needed to do is every so often they need to have one big breath. So you have a couple of

00:16:27.440 | minutes of normal breaths and then one big breath, just mimicking the physiological size. And then the

00:16:33.440 | mortality rate dropped significantly. And if you see someone on a ventilator in the hospital,

00:16:41.280 | if you watch, every couple of minutes that you see the membrane move up and down, every couple of

00:16:45.920 | minutes there'll be a super breath. And that pops it open. So there are these mechanisms for these

00:16:52.640 | physiological size. So just like with the collapse of the lungs where you need a big pressure to pop it

00:17:01.440 | open, it's the same thing with the alveoli. You need a bigger pressure and a normal breath is not enough.

00:17:07.360 | So you have to take a big inhale. And when nature is done is instead of requiring us to remember to do it,

00:17:16.160 | it does it automatically. And it does it about every five minutes.

00:17:20.480 | We hear often that people will overdose on drugs of various kinds because they stop breathing.

00:17:26.560 | So barbiturates, alcohol combined with barbiturates is a common cause of death for drug users and

00:17:33.840 | contraindications of drugs and these kinds of things. You hear all the time about celebrities

00:17:38.800 | dying because they combined alcohol with barbiturates. Is there any evidence that the

00:17:43.760 | size that occur during sleep or during states of, you know, deep, deep relaxation

00:17:51.840 | and sedation that size recover the brain? Because you can imagine that if these size don't happen

00:18:00.400 | as a consequence of some drug impacting these brain centers, that that could be one cause of basically

00:18:06.080 | asphyxiation and death. If you look at the progression of any mammal to a death due to quote

00:18:15.600 | natural causes, their breathing slows down. It's will stop and then they'll gasp. So we have the phrase dying gasp.

00:18:24.640 | Super large breaths. They're often described as an attempt to auto resuscitate.

00:18:31.520 | That is, you take that super deep breath and that maybe it can kickstart the engine again.

00:18:38.000 | We do not know the degree to such things as gasp are really size that are particularly large. And so

00:18:46.720 | if you suppress the ability to gasp in an individual who is subject to an overdose, then whereas they might

00:18:56.560 | been able to re-arouse their breathing, if that's prevented, they don't get re-aroused. So that is

00:19:04.160 | certainly a possibility. I'd love to get your thoughts on how breathing interacts with other

00:19:10.880 | things in the brain. As we know, when we get stressed, our breathing changes. When we're happy

00:19:16.960 | and relaxed, our breathing changes. But also, if we change our breathing, we, in some sense,

00:19:23.920 | can adjust our internal state. What is the relationship between brain state and breathing?

00:19:29.360 | This is a topic which has really intrigued me over the past decade. I would say before that,

00:19:36.080 | I was in my silo just interested about how the rhythm of breathing is generated and didn't really pay much

00:19:42.400 | attention to this other stuff. For some reason, I got interested in it. I felt maybe I can study this in

00:19:49.120 | rodents. So we got this idea that we're going to teach rodents to meditate. And, you know, that's laughable.

00:19:58.080 | But we said, but if, but if we can, then we can actually study how this happens. So I was able to

00:20:06.000 | get a sort of a starter grant, an R21 from NCCIH. That's the National Complementary Medicine Institute.

00:20:15.200 | A wonderful institute I should mention. Our government puts major tax dollars

00:20:21.360 | toward studies of things like meditation, breath work, supplements, herbs, acupuncture. This is,

00:20:28.080 | I think, not well known. And it's an incredible thing that this, that our government does that. And I

00:20:35.520 | think it deserves a nod. I totally agree with you. I think that it's the kind of thing that many of us,

00:20:41.280 | including many neuros, many scientists, thinks is too woo-woo and unsubstantiated. But we're learning

00:20:48.000 | more and more. You know, we used to laugh at neuroimmunology. There were all these things that

00:20:52.240 | we're learning that we used to dismiss. And I think there's, there's real nuggets to be learned here.

00:20:58.880 | So recently we had a major breakthrough. We found a protocol by which we can get awake mice to breathe

00:21:06.080 | slowly. In other words, whatever their normal breath is, we could slow it down by a factor of 10. And

00:21:11.680 | they're fine doing that. We did that 30 minutes a day for four weeks. Okay. Like a breath practice.

00:21:19.280 | And we had control animals where we did everything the same, except the manipulation we made did not slow

00:21:27.120 | down their breathing. We then put them to a standard fear conditioning, which we did with my colleague,

00:21:31.840 | Michael Fanzelow, who's one of the real gurus of fear. We measured a standard test that put mice in

00:21:38.880 | a condition where they're concerned that we receive a shock and their response is that they freeze. And

00:21:46.320 | the measure of how fearful they are is how long they freeze. The control mice had a freezing time, which was

00:21:54.160 | just the same as ordinary mice would have. The ones that went through our protocol froze much,

00:22:00.560 | much less. The degree to which they were showed less freezing was as much as if there was a major

00:22:08.160 | manipulation in the amygdala, which is a part of the brain that's important in fear processing.

00:22:12.880 | Michael Fanzelow: I'll just pause you for a moment there because I think that the, you know, you're

00:22:16.480 | talking about a rodent study, but I think the, the benefits of doing rodent studies that you can get

00:22:21.040 | deep into mechanism. Um, and for people that, um, might think, well, we've known that meditation has

00:22:28.400 | these benefits. Why do you need to get mechanistic science? I think that, uh, one thing that's important

00:22:33.520 | for people to remember is that, first of all, as many people as one might think, uh, are meditating out

00:22:39.920 | there or doing breath work for a far, far, far greater number of people are not right. I mean,

00:22:45.520 | there's a, the majority of people don't take any time to do dedicated breath work nor meditate. Um,

00:22:52.800 | so whatever can incentivize people would be a wonderful. But the other thing is that it's never

00:22:59.040 | really been clear to me just how much meditation is required for a real effect, meaning a practical

00:23:05.520 | effect. People say 30 minutes a day, 20 minutes a day, once a week, twice a week, same thing with

00:23:09.920 | breath work. Um, finding minimum or effective thresholds for changing neural circuitry is what

00:23:16.960 | I think is the holy grail of all these, uh, practices. And that's only going to be determined

00:23:21.520 | by the sorts of mechanistic studies that you describe. One of the, uh, issues I think for a lot of people

00:23:26.800 | is that there's a placebo effect. That is in humans, they can respond to something, even though the

00:23:34.000 | mechanism has nothing to do with what the, the, the intervention is. And so it's easy to say that the

00:23:41.360 | meditative response is a, has a big component, which is a placebo effect. My mice don't believe

00:23:47.920 | in the placebo effect. And so if we could show there's a bona fide effect in mice, it is convincing

00:23:55.040 | in ways that no matter how many human experiments you did to control for the placebo effect is extremely

00:24:00.480 | difficult in humans. In mice, it's, it's a non-issue. So I think that that in of itself would be an

00:24:07.760 | enormous message to send. Excellent. And indeed, uh, a better point, a 30 minute a day meditation,

00:24:14.800 | um, in these mice, if I understand correctly, the meditation, we don't know what they're thinking about.

00:24:20.320 | It's breath practice. Right. So it's breath practice. So they're, because we don't, they're,

00:24:24.000 | presumably they're not thinking about their third eye center, lotus position, levitation, whatever it is.

00:24:28.400 | They're not instructed as to what to do. And if they were, they probably wouldn't do it anyway.

00:24:32.720 | So 30 minutes a day in which breathing is deliberately slowed or is slowed relative to

00:24:38.640 | their normal patterns of breathing. Got it. So the fear centers are altered in some way that creates,

00:24:45.520 | uh, a shorter fear response to a foot shock. Right. What are some other examples that you are aware of

00:24:51.760 | from work in your laboratory or work in other laboratories for that matter, about interactions

00:24:56.240 | between breathing and brain state or emotional state? I want people to understand that when we're talking

00:25:02.320 | about breathing affecting emotional cognitive state, it's not simply coming from pre-Butzinger. There are

00:25:09.360 | several other sites. And let me sort of, I need to sort of go through that. One is olfaction. So when

00:25:15.840 | you're breathing, normal, normal breathing, you're inhaling and exhaling. This is creating signals coming from the

00:25:23.680 | nasal mucosa that is going back into the olfactory bulb that's respiratory modulated. And the olfactory

00:25:32.240 | bulb has a profound influence and projections through many parts of the brain. So there's a signal arising from

00:25:40.560 | this rhythmic moving of air in and out of the nose that's going into the brain that has contained in it a

00:25:47.360 | respiratory modulation. Another potential source is the vagus nerve. The vagus nerve is a major nerve

00:25:54.960 | which is containing afferents from all of the viscera. Afferents just being a signal. Signals too.

00:26:02.480 | Yeah. Signals from the viscera. It also has signals coming from the brain stem down, which are called

00:26:08.240 | efferents. But it's getting major signals from the lung, from the gut. And this is going up into the brain stem.

00:26:17.040 | So it's there. There are very powerful receptors in the lung. They're responding to the expansion

00:26:24.960 | and relaxation of the lung. And so if you record from the vagus nerve, you'll see that there's a huge

00:26:30.800 | respiratory modulation due to the mechanical changes in the lung. Now, why that is of interest is that for

00:26:40.320 | some forms of refractory depression, electrical stimulation of the vagus nerve can provide tremendous

00:26:47.920 | relief. Why this is the case still remains to be determined. But it's clear that signals in the vagus

00:26:55.760 | nerve, at least artificial signals in the vagus nerve, can have a positive effect on reducing depression.

00:27:02.720 | So it's not elite to think that under normal circumstances, that that rhythm coming in from

00:27:09.120 | the vagus nerve is playing a role in normal processing. Okay, let me continue. Calmed oxide and

00:27:16.800 | oxygen levels. Now, under normal circumstances, your oxygen levels are fine. And unless you go to altitude,

00:27:25.200 | they don't really change very much. But your CO2 levels can change quite a bit with even a relatively

00:27:31.920 | small change in your overall breathing. That's going to change your pH level. I have a colleague,

00:27:37.280 | Alicia Marat, who is working with patients who are anxious. And many of them hyperventilate. And as a

00:27:48.240 | result of that hyperventilation, their carbon dioxide levels are low. She has developed a therapeutic treatment

00:27:55.600 | where she trains these people to breathe slower to restore their CO2 levels back to normal. And

00:28:04.240 | she gets relief in their anxiety. So CO2 levels, which are not going to affect brain function on a

00:28:11.040 | breath-by-breath level, although it does fluctuate breath-by-breath, but sort of as a continuous

00:28:16.160 | background, can change. And if it's changed chronically, we know that highly elevated levels of CO2

00:28:23.760 | can produce panic attacks. Your body is so sensitive, the control of breathing, like how much you breathe per

00:28:31.360 | per minute is determined in a very sensitive way by the CO2 level. So even a small change in your CO2

00:28:39.520 | will have a significant effect on your ventilation. So this is another thing that not only changes your

00:28:46.560 | ventilation, but affects your brain state. Now, another thing that can affect how breathing practice can

00:28:54.160 | affect your emotional state is simply the descending command. Because breathing practice involves

00:29:01.040 | volitional control of your breathing. And therefore, there's a signal that's originating somewhere in

00:29:07.600 | your motor cortex. That is not, of course, that's going to go down to pre-Butzinger, but it's also going to send

00:29:14.560 | off collaterals to other places. Those collaterals could obviously influence your emotional state.

00:29:19.520 | So we have quite a few different potential sources, none of them that are exclusive.

00:29:26.000 | What are some of the other features of our brain and body, be it blinking, or eye movements, or

00:29:35.760 | ability to encode sounds, or any features of the way that we function and move and perceive things

00:29:44.800 | that are coordinated with breathing in some interesting way?

00:29:48.720 | Dr. Almost everything. So we have, for example, on the autonomic side, we have respiratory sinus arrhythmia.

00:29:56.960 | That is, during expiration, the heart slows down. Your pupils oscillate with the respiratory cycle.

00:30:05.200 | Your fear response. Let's take something like depression. You can envision depression

00:30:13.360 | as activity sort of going around in a circuit. And because it's continuous in the nervous system,

00:30:20.960 | as signals keep repeating, they tend to get stronger. And they can get so strong, you can't

00:30:27.040 | break them. And I mean, all of us get depressed at some point. But if it's not continuous, it's not long

00:30:32.480 | lasting, we're able to break it. Well, there are extreme measures to break it. We could do electroconvulsive

00:30:39.760 | shock. We've shocked the whole brain. That's disrupting activity in the whole brain. And when

00:30:45.200 | the circuit starts to get back together again, it's been disruptive. And we know that the brain, when

00:30:52.560 | signals get disrupted a little bit, we can weaken the connections. And weakening the connections,

00:30:58.320 | if it's that in the circuit involved in depression, we may get some relief. And electroconvulsive shock

00:31:04.400 | does work for relieving many kinds of depression. Focal deep brain stimulation does the same thing,

00:31:11.520 | but more localized or transcranial stimulation. You're disrupting a network. And while it's getting back

00:31:18.560 | together, it may weaken some of the connections. If breathing is playing some role in this circuit,

00:31:27.920 | and now instead of doing like a, you know, one second shock, I do 30 minutes of disruption by

00:31:34.880 | doing slow breathing or other breathing practice. The, those circuits begin to break down a little bit

00:31:42.800 | and I get some relief. And if I continue to do it before the circuit can then build back up again,

00:31:50.160 | I gradually can wear that circuit down. I, I sort of liken this. I tell people it's like walking around

00:31:56.240 | on a dirt path, you build a rut to rut gets so deep, you can't get out of it. And what breathing is doing

00:32:02.160 | is sort of filling in the rut bit by bit to the point that you can climb out of that rut. And that is because

00:32:08.640 | breathing, the breathing signal is playing some role in the way the circuit works. And then when you

00:32:18.000 | disrupt it, the circuit gets a little thrown off kilter. And when, as you know, when this, when circuits get

00:32:24.320 | thrown off, the nervous system tries to adjust in some way or another. And it turns out, at least for

00:32:31.120 | breathing, for some evolutionary reason, or just by happenstance, it seems to improve our emotional

00:32:37.920 | function or our cognitive function. And, you know, we're very fortunate that that's the case.

00:32:43.360 | What do you do with all this knowledge in terms of a breathing practice?

00:32:49.200 | I find I get tremendous benefit by relatively short periods between five and maybe 20 minutes

00:32:58.000 | of doing box breathing. It's very simple to do. I'm now trying this two mole because I'm just curious and

00:33:07.600 | exploring it because it may be acting for a different way. And I want to see if I respond differently.

00:33:14.480 | I have friends and colleagues who are into, you know, particular styles like Wim Hof. And I think what

00:33:21.440 | he's doing is great and getting people who are interested. I think the notion is that I would like to see

00:33:28.960 | more people exploring this. And to some degree, as you point out, 30 minutes a day, some of the breath

00:33:37.040 | patterns that some of these styles like Wim Hof are a little intimidating to newbies. And so I would like

00:33:46.480 | to see something very simple that people, what I tell my friends is, look, just try it five or 10 minutes.

00:33:51.280 | See if you feel better. Do it for a few days. If you don't like it, stop it. It doesn't cost anything.

00:33:56.160 | And invariably they find that it's helpful. I will often interrupt my day to take five or 10 minutes.

00:34:05.840 | Like if I find that I'm lagging, you know, I think there's some pretty good data that your performance after

00:34:14.000 | lunch declines. And so very often what I'll do after lunch is take five or 10 minutes and just sort of

00:34:21.280 | breath practice. And lately, what does that breath practice look like? It's just box breathing for

00:34:26.720 | five or 10 minutes. So five seconds, inhale, five second, hold, five second, exhale, five, five.

00:34:32.080 | Yeah. And sometimes I'll do doubles. I'll do 10 seconds. Um, just because I, I, I get bored,

00:34:40.000 | like, you know, it's just nice. I feel like doing it and it's, it's, um, it's very, it's very helpful.

00:34:46.640 | You know, you're one of the few colleagues I have who openly admits to, uh, exploring supplementation.

00:34:54.560 | Um, I'm a long time, uh, supplement fan. I think there, there's power in compounds,

00:35:00.880 | both prescription, non-prescription, natural synthesized. Uh, I don't use these haphazardly,

00:35:07.600 | but I think there's certainly power in them. And one of the places where you and I converge is

00:35:12.000 | in terms of our interest in the nervous system and supplementation is, uh, vis-a-vis magnesium.

00:35:18.400 | Now I've talked at, you know, endlessly, uh, on the podcast and elsewhere about magnesium for

00:35:24.960 | sake of sleep and improving transit transitions to sleep and, and so forth. But you have a, uh,

00:35:30.400 | somewhat different interest in magnesium as it relates to cognitive function and durability of

00:35:36.480 | cognitive function. Would you mind just sharing with us a little bit about what that interest is,

00:35:40.720 | where, where it stems from? And because it's this, because it's the Huberman lab podcast and we often

00:35:46.240 | talk about supplementation, what, um, what you do with that information?

00:35:50.560 | So I need to disclose that I am a scientific advisor to a company called Neurocentria, which my graduate

00:35:58.320 | student, Kuo-Sung Liu, was CEO. Um, so that said, I can give you some background. Kuo-Sung, uh, although he,

00:36:06.640 | when he was in my lab, worked on breathing, had a deep interest in learning and memory. And when he left my lab,

00:36:12.880 | he went to work for it with a renowned learning and memory guy at Stanford, Dick Chen. And when he,

00:36:20.000 | um, finished there, he was hired by Susumu Tanagawa at MIT.

00:36:24.880 | Who also knows a thing or two about memory. I'm teasing. Susumu has a Nobel for his work on

00:36:30.640 | immunoglobulins, but then as a world-class memory researcher. Yeah. Um, and more, um,

00:36:38.400 | he's many things and, and Kuo-Sung had very curious, very bright guy. And he was interested in how signals

00:36:48.560 | between neurons get strengthened, which is called long-term potentiation or LTP. And one of the,

00:36:56.000 | the questions that arose was if I have inputs to a neuron and I get LTP, is the LTP bigger if the signal

00:37:08.480 | is bigger or the noise is less? So we can imagine that, uh, when we're listening to something, if it's

00:37:15.680 | louder, we can hear it better. Or if there's less noise, we can hear it better. And he wanted to

00:37:20.960 | investigate this. So he did this in tissue culture of hippocampal neurons. And what he found was that

00:37:29.120 | if he lowered the background activity in all of the neurons, that the LTP he elicited got stronger.

00:37:40.640 | And the way he did that was increasing the level of magnesium in the bathing solution.

00:37:46.880 | So he played around with the magnesium and he found out that when the magnesium was elevated,

00:37:52.240 | there was more LTP. All right. That's an observation in a tissue culture.

00:37:57.360 | Right. And I should just mention that more LTP

00:37:59.680 | essentially translates to more neuroplasticity, more rewiring of connections in essence.

00:38:05.520 | So he, um, tested this in mice and basically he offered them a, um, uh, he had control mice,

00:38:17.520 | which got a normal diet and one that had, one that reached the magnesium and the ones that lived,

00:38:22.560 | uh, enriched with magnesium had higher cognitive function, uh, live longer, everything you'd want

00:38:29.280 | in some magic pill. Those mice did that, excuse me, rats. Um, the problem was that you couldn't

00:38:40.240 | imagine taking this into humans because most magnesium salts don't passively get from the gut

00:38:49.120 | into the bloodstream, into the brain. They pass via a, what's called a transporter. Transporter is

00:38:55.840 | something in a membrane that grabs a, uh, magnesium molecule or atom and pulls it into the other side.

00:39:05.440 | So if you imagine you have magnesium in your gut, you have transporters that pull the magnesium into

00:39:10.640 | gut into the bloodstream. Well, if you had taken normal magnesium supplement that you can buy at the

00:39:17.600 | pharmacy, it doesn't cross the gut very easily. And if you would take enough of it to get it in your

00:39:24.720 | bloodstream, you start getting diarrhea. So it's not a, uh, a good way to go.

00:39:30.800 | Oh, it is a good way to go. Sorry. Couldn't help myself.

00:39:34.640 | Uh, well said. Um, so he worked with this brilliant chemist, Fay Mao. And, um, Fay

00:39:48.240 | looked at a whole range of magnesium compounds and he found that magnesium threonate was much more

00:39:54.400 | effective in crossing the, uh, gut blood barrier. Now they didn't realize at the time, but threonate

00:40:03.200 | is a metabolite of vitamin C. And there's lots of threonate in your body. So magnesium threonate would

00:40:10.000 | appear to be safe and maybe, uh, part of the role or the, now they believe it's part of the role of the

00:40:18.240 | threonate is that it supercharges the transporter to get the magnesium in. And remember, you need a

00:40:24.720 | transporter at the gut into the brain and into cells. They did a study in humans. They hired a, um, a company to

00:40:34.560 | do a test. There was a hands-off test. It's one of these companies that gets hired by the big pharma to

00:40:40.320 | do their tests for them. And they got patients who had, were diagnosed as mild cognitive decline. These

00:40:49.120 | are people who had cognitive disorder, which was age inappropriate. And the, the metric that they use

00:40:56.640 | for determining how far off they were is Spearman's G factor, which is a generalized measure of intelligence

00:41:07.120 | that most psychologists accept. And the biological age of the subjects was, I think, 51. And the cognitive

00:41:21.360 | age was 61 based on the Spearman's G test. I should say the Spearman's G factor starts at a particular

00:41:28.400 | level in the population at age 20 and declines about 1% a year. So sorry to say we're not 20 year olds anymore.

00:41:39.840 | But when you get a number from that, you can put on the curve and see whether it's about your age or not.

00:41:47.440 | These people were about 10 years older according to that metric. And long story short, after three months,

00:41:57.440 | this is a placebo controlled double blind study. The people who are in the placebo arm improved two years,

00:42:06.400 | which is common for human studies because of placebo effect. The people who got the compound improved eight

00:42:16.160 | years on average and some improved more than eight years. They didn't do any further diagnosis as to

00:42:22.720 | what caused the Molokov decline, but it was pretty, it was extraordinarily impressive.

00:42:27.200 | So it moved their cognition closer to their biological age, biological age.

00:42:31.840 | Um, do you recall what the doses of magnesium three and it's in the, it's in the paper and it's

00:42:37.280 | basically what they have in the compound, which is sold commercially. So the compound, which is sold

00:42:43.840 | commercially is, uh, handled by a nutraceutical wholesaler who sells it to the retailers and they

00:42:52.320 | make whatever formulation they want. Um, but, um, it's, it's a dosage, which, uh, is,

00:43:00.080 | my understanding is rarely tolerable. I take half a dose. The reason I take half a dose is that I had my

00:43:08.960 | magnesium blood magnesium measured and, um, it was low normal for my age. I took half a dose and became high

00:43:18.960 | normal and I felt comfortable staying in the normal range. Um, but, you know, a lot of people are taking

00:43:27.200 | the full dose and, uh, and, um, at my age, I'm not looking to get smarter. I'm looking to decline more

00:43:36.560 | slowly. And it's hard as, you know, it's hard for me to tell you whether or not it's effective or not.

00:43:41.920 | When I've recommended it to my friends, academics who were not by nature skeptical, if not cynical,

00:43:49.440 | and insist that they try it, they usually don't report a major change in their cognitive function,

00:43:56.400 | although sometimes they do report, well, I feel a little bit more alert and my move, my physical

00:44:02.080 | movements are better, but many of them report they sleep better. Yeah. And, and that makes sense. I

00:44:08.240 | think, uh, there's good evidence that three and eight can, uh, accelerate the transition into sleep and

00:44:13.760 | maybe even, uh, access to deeper, um, modes of sleep. But this, that's very interesting because I,

00:44:20.160 | until you and I had the discussion about three and eight, I wasn't, um, aware of the, uh, cognitive

00:44:26.960 | enhancing effects, but the story makes sense from a mechanistic perspective. And it brings it around to a

00:44:32.960 | bigger and more important statement, which is that I so appreciate your attention to mechanism. I guess

00:44:40.640 | this stems from your early training as a physicist and the desire to get numbers and, and to really, uh,

00:44:46.720 | parse things at a fine level. We've covered a lot today. I know there's much more that we could cover.

00:44:51.360 | I'm going to insist on a part two at some point, but I really want to speak on behalf of a huge number of

00:44:58.480 | people. And just thank you, not just for your time and energy and attention to detail and accuracy and

00:45:03.680 | clarity around this topic today, but also what I should have said at the beginning, which is that,

00:45:09.280 | you know, you really are a pioneer in this field of studying respiration and the mechanisms underlying

00:45:15.680 | respiration with modern tools for now for many decades. I really want to extend a sincere thanks.

00:45:22.000 | It means a lot to me. And I know to the audience of this podcast, as someone with your depth and rigor

00:45:27.920 | in this area is both a scientist and a practitioner, and that you would share this with us. So thank

00:45:33.200 | you. I appreciate the opportunity and I would be delighted to come back at any time.

00:45:38.240 | Wonderful. We will absolutely do it. Thanks again, Jack. Bye now.

Essentials: Breathing for Mental & Physical Health & Performance | Dr. Jack Feldman

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