Using Salt to Optimize Mental & Physical Performance | Huberman Lab

Andrew Huberman 0:00 (instrumental music) Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. Today, we are going to discuss salt, also referred to as sodium. Now, most of think of salt as something that we put on and in our food, maybe something to avoid. Maybe some of you are actually trying to get more salt. Some of you are trying to get less salt. We all seem to associate salt with things like blood pressure, et cetera. Today, we are going to go down a different set of avenues related to salt. We will certainly cover how salt regulates blood pressure. We are also going to talk about how the brain regulates our appetite for salt or our aversion for salt. We are also going to talk about how our sensing of salty tastes actually mediates how much sugar we crave and whether or not we ingest more or less sugar than we actually need. So, what you're going to learn today is that the so-called salt system, meaning the cells and connections in our brain and body that mediate salt craving and avoidance, are regulating many, many aspects of our health and our ability to perform in various contexts, things like athletic performance, things like cognitive performance. We're also going to talk about aging and dementia, and avoiding aging and dementia, and what role salt and salt avoidance might play in that. We're going to touch on some themes that for some of you might seem controversial, and indeed, if they are controversial, I'll be sure to highlight them as such. I'm going to cover a lot of new data that point to the possibility, I want to emphasize, the possibility, that for some people, more salt might help them in terms of health, cognitive, and bodily functioning, and for other people, less salt is going to be better. I'm gonna talk about what the various parameters are. I'm going to give you some guidelines that, in concert with your physician, who you should absolutely talk to before adding or changing anything to your diet or supplementation regime, can help you arrive at a salt intake that's going to optimize your mental, physical health and performance. So, we're going to cover neurobiology. We're going to cover hormone biology. We're going to talk about liver function. We're going to talk about kidney function, and of course, brain function. I'm excited to share this information with you today. I'm certain you're going to come away with a lot of information and actionable items.

Andrew Huberman 2:18 I'm pleased to announce that I'm hosting two live events this May. The first live event will take place in Seattle, Washington on May 17th. The second live event will take place in Portland, Oregon on May 18th. Pre-sale tickets for these two events are now available at hubermanlab.com/tour. I should mention that while I do hope to visit other cities in the near future to do more live events, right now, these are the only two live events I have scheduled, at least for the next six months. So once again, if you go to hubermanlab.com/tour, you can access the pre-sale tickets. I hope to see you at these live events, and as always, thank you for your interest in science. Before we dive into the topic of today's episode,

Andrew Huberman 2:57 I want to highlight a really exciting new study. This is a study from Diego Bohorquez' lab at Duke University. The Bohorquez lab studies interactions between the gut and the brain, and has made some incredible discoveries of the so-called neuropod cells. Neuropod cells are neurons, nerve cells, that reside in our gut and that detect things like fatty acids, amino acids, and some neuropod cells sense sugar. Previous work from this laboratory has shown that when we ingest sugar, these neuropod cells respond to that sugar and send electrical signals up a little wire that we call an axon through the vagus nerve, for those of you that want to know, and into the brain, and through subsequent stations of neural processing, evoke the release of dopamine. Dopamine is a molecule known to promote craving and motivation, and indeed action, and what these neuropod cells that send sugar are thought to do is to promote seeking and consumption, eating, of more sugary foods. Now, the incredible thing is that it's all subconscious. This is a taste system in the gut that is not available to your conscious awareness. Now, of course, when you ingest sweet foods, you taste them on your mouth too, and so part of the reason that you crave sweet foods perhaps is because they taste good to you, and the other reason is that these neuropod cells are driving a chemical craving below your conscious detection. So, there are really two systems. Your gut is sensing, at a subconscious level, what's in it, and sending signals to your brain that work in concert, in parallel with the signals coming from your mouth and your experience of the taste of the food. Now, that alone is incredible and has been the subject of many important landmark papers over the last decade or so. You can imagine how this system would be very important for things like hidden sugars, when nowadays in a lot of processed foods, they're putting hidden sugars. Uh, they're putting a lot of things that cause your gut to send signals to your brain that make you crave more of those foods. So, for those of you that really love sugar, just understand, it's not just about how that sugar tastes. The new study from the Bohorquez lab deserves attention, I believe. This is a paper published just recently, February 25th this year, 2022, in Nature Neuroscience, an excellent journal, and the title of the paper is The Preference for Sugar over Sweetener Depends on a Gut Sensor Cell. The Bohorquez lab has now discovered a neuropod cell, meaning a category of neurons, that can distinguish between sweet things in the gut that contain calories, for instance, sugar, and things in the gut that are sweet, but do not contain calories, artificial sweeteners like aspartame, sucralose, and so forth. There are also, of course, non-artificial, non-caloric sweeteners like stevia, monk fruit, et cetera. They did not explore the full gallery of artificial sweeteners. What they did find, however, ought to pertain to all forms of sweet non-caloric substances. What they discovered was that there is a signature pattern of signals sent from the gut to the brain when we ingest.... artificial or non-caloric sweeteners. This is important because what it says is that at a subconscious level, the gut can distinguish between sweet things that contain calories and sweet things that do not. Now, what the downstream consequences of this sensing is, or what they are, isn't yet clear. Now, I believe everyone should be aware of these kinds of studies for a couple of reasons. First of all, it's important to understand that what you crave, meaning the foods you crave and the drinks you crave, is in part due to your conscious experience of the taste of those things, but also due to biochemical and neural events that start in the body and impinge on your brain and cause you to seek out certain things, even though you might not know why you're seeking out more sugar. You find that you're craving a lot of sugar or you're craving a lot of foods with artificial sweeteners, and you don't necessarily know why. Now, artificial sweeteners themselves are a somewhat controversial topic. I want to highlight that. Some months back, I described a study from Yale University about how one can condition the insulin system. Insulin is involved in mobilizing of blood sugar and so forth in the body, as many of you know, and I described some studies that were done from Yale University School of Medicine looking at how artificial sweeteners can actually evoke an insulin response under certain conditions. Now, a couple of key things. I got a little bit of pushback after covering those studies, and I encourage pushback all the time. It's, you know, pushback is one of those things that forces all of us to drill deeper into a topic. I want to be clear. First of all, I am not one to demonize artificial sweeteners. There is evidence in animal models, in animal models, that artificial sweeteners can disrupt the gut microbiome, but those were fairly high doses of artificial sweeteners and it's unclear if the same thing pertains to humans. Still unclear, I should say. Has not been investigated thoroughly. Some people don't like the taste of artificial sweeteners. Some people do. Some people find that they really help them avoid excessive caloric intake. Some people believe, and yet I should emphasize there still isn't evidence that they can adjust the insulin response in all people. I just want to repeat that three times so that, uh, people are clear on that fact. What these new data emphasize, however, is that we need to understand how artificial sweeteners are consumed at the level of the gut, or I should say registered at the level of the gut, and how that changes brain function. Because one thing that I'm familiar with and that many people report is that when you, they first taste artificial sweeteners, they taste sort of not right to them. They don't like the taste, but over time, they actually start to crave that taste. I've experienced this. I used to drink a lot of diet sodas when I was in graduate school, so this would be aspartame, and I found that I would nee- I actually needed them. Now, maybe it was the caffeine. Maybe I just liked the sweet taste of the carbonation. We actually have an, a, a drive for carbonation, which is a topic of a future episode. But when I finally quit them for reasons that were independent of any fear of artificial sweeteners, I found that I didn't like the taste. Nowadays, I only occasionally drink a diet soda. I usually do that if I'm on a plane and there's nothing else available to me. So I don't demonize them. I might, uh, drink one every once in a while. No big deal. I also want to be clear, I consume stevia in a number of different, uh, supplements and foods that I consume. Stevia, of course, is a plant-based non-caloric sweetener. So I myself consume artificial sweeteners. Many people hate them. Many people like them and find them useful for their nutrition and, in fact, to keep their caloric intake in a range that's right for them. And many people, like myself, are curious about them and somewhat wary of them, and yet continue to consume them in small amounts. I think most people probably fall into that category. I should also mention that many food manufacturers put artificial sweeteners such as sucralose, et cetera, into foods and it's always been unclear as to why they might want to do that. And yet we know that the sweet taste consumption, even if it doesn't contain calories, can drive more craving of sweet food. So there may be a logic or a strategy to why they do that. Again, a topic for exploration on today's podcast and in future podcasts, because where we're headed today is a discussion about how salt and salt sensing, both consciously and unconsciously, can adjust our craving for other things like sugar and water and so on. So I want to highlight this beautiful work from the Bohorquez Lab. We'll put a link to the study. I want to g- open this as a chapter for further exploration. I like to think that the listeners of this podcast are looking for answers where we have answers, but are also, I would hope, excited about some of the new and emerging themes in what we call nutritional neurobiology and indeed, the Bohorquez Lab really stands as one of the premier laboratories out there that's looking at how foods, as consumed in the gut, are modifying our nervous system, the foods we crave, and how we utilize those foods. Before

Andrew Huberman 10:57 we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero cost to consumer information about science and science related tools to the general public. In keeping with that theme, I'd like to thank the sponsors of today's podcast. Our first sponsor is Athletic Greens, now called AG1. I've been taking AG1 since 2012, so I'm delighted that they're sponsoring the podcast. The reason I started taking AG1 and the reason I still take AG1 once or twice a day is that I find it to be the best way to ensure I get all of my vitamins and minerals and the probiotics I need. I try and eat really well, but I'm not perfect about it, and with Athletic Greens, AG1, I cover any deficiencies I might have. The probiotics are particularly important to me because as we've talked about on many previous episodes, and we'll talk about more on today's episode, the gut microbiome is supported by probiotics and the gut microbiome supports many biological functions important for immediate and long-term health. Things like immune system function, things like the gut brain axis and mood and appetite and so forth. With Athletic Greens, I make sure all of those bases are covered because of the probiotics. If you'd like to try Athletic Greens, you can go to athleticgreens.com/huberman to claim a special offer. They'll give you five free travel packs, which make it really easy to mix up-... Athletic Greens while you're on the road, and they'll give you a year's supply of vitamin D3 K2. Vitamin D3 is crucial for many aspects of our immediate and long-term health, and many people simply are not getting enough vitamin D3, or the amounts they're getting are not optimal. K2 is important for cardiovascular health and for calcium regulation. So again, if you go to athleticgreens.com/huberman, you can claim this special offer of the five free travel packs and a year's supply of vitamin D3 K2. Today's episode is also brought to us by LMNT. LMNT is an electrolyte drink that has everything you need and none of the things you don't. That means it has salt, magnesium, and potassium, so-called electrolytes, which are critical for neuronal function and a lot of other biological functions. As I mentioned on the podcast before, I'm a fan of salt. I believe in ingesting appropriate amounts of salt, and by appropriate, I mean depending on what your background blood pressure happens to be, what your activity levels are, how much you sweat, what your cognitive and physical demands are. Today, we're going to talk about how to determine what those needs are. I'm always trying to stay on top of my hydration, and as you'll also learn about today, salt and water intake and hydration are intimately related. With LMNT, I'm sure to get the potassium, the sodium, and the magnesium that I need, and I do that in a great-tasting drink, and as I mentioned before, it has no sugar. If you'd like to try LMNT, you can go to drinklmnt.com, that's drink L-M-N-T dot com, /huberman to claim a free LMNT sample pack. You only cover the cost of shipping, otherwise it's completely free. Again, that's drink LMNT, L-M-N-T dot com /huberman to claim a free sample pack of LMNT. Today's episode is also brought to us by InsideTracker. InsideTracker is a personalized nutrition platform that analyzes data from your blood and DNA to help you better understand your body and help you reach your health goals. I am a big fan of getting regular blood work done, and I've been trying to do it as much as I can afford for years. The reason is that many of the factors that impact our immediate and long-term health can only be discovered from a quality blood test. With most blood tests and DNA tests, however, you get information back, but not a lot of information about what to do with those numbers. So if something's in high or low range, you might get one or two generic recommendations, things that you could easily look up online, but you're not going to get a lot of specific recommendations. With InsideTracker, they give you a lot of specific recommendations as to lifestyle factors, nutrition factors, supplementation factors, things you may want to add to your life or things you may want to delete from your life in order to bring the numbers into the ranges that are best for your immediate and long-term health. There's simply no replacement for these kinds of data, and your data are the most important data to you, and quality blood tests and DNA tests are the way to access them. If you'd like to try InsideTracker, go to insidetracker.com/huberman to get 20% off any of InsideTracker's plans. That's insidetracker.com/huberman to get 20%

Andrew Huberman 15:06 off. Okay, let's talk about salt. Salt has many, many important functions in the brain and body. For instance, it regulates fluid balance, how much fluid you desire and how much fluid you excrete. It also regulates your desire for salt itself, meaning your salt appetite. You have a homeostatically driven salt appetite. I'll talk about the mechanisms today and make them all very clear. What that means is that you crave salty things, beverages and foods, when your salt stores are low, and you tend to avoid salty beverages and foods when your salt stores are high, although that's not always the case. There are circumstances where you will continue to crave salt even though you don't need salt or indeed even if you need to eliminate salt from your system. Salt also regulates your appetite for other nutrients, things like sugar, things like carbohydrates, and today we'll explore all of that. Technically, salt is a mineral, and I should mention that when I say salt, I am indeed referring to sodium in most cases, although I will be clear to distinguish salt from sodium, meaning f- table salt from sodium. Most people don't realize this, but one gram of table salt contains about 388 milligrams of sodium. So technically, we should be talking about sodium today and not salt. I will use them interchangeably unless I'm referring to some specific recommendations or ideas about trying to define your ideal salt, AKA sodium, intake. Okay? So this is important. I think right off the bat, a lot of people s- get themselves into a place of confusion and potentially even to a place of trouble by thinking that table salt in grams always equates to sodium in grams, and that's simply not the case. Today we're going to explore the neural mechanisms by which we regulate our salt appetite and the way that the brain and body interact in the context of salt seeking, salt avoidance, how to determine when we need more salt, when we need less salt. We'll talk about kidney function. We'll get into all of it and we're going to do it

Andrew Huberman 17:13 very systematically. So let's start in the brain. We all harbor small sets of neurons. We call these sets of neurons nuclei, meaning little clusters of neurons that sense the levels of salt in our brain and body. There are a couple brain regions that do this, and these brain regions are very, very special, special because they lack biological fences around them that other brain areas have, and the- those fences, or I should say that fence, goes by a particular name and that name is the blood-brain barrier or BBB. Most substances that are circulating around in your body do not have access to the brain, in particular large molecules can't just pass into the brain. The brain is a privileged organ in this sense. There are a couple other organs that are privileged and that have very strict barriers, very particular fences if you will, and those other organs include things like the ovaries and testes, and that makes sense for the following reason. First of all, the brain, at least most of the brain, cannot regenerate.... after injury. You just simply can't replace brain cells after injury. I know people get really excited about neurogenesis, the birth of new neurons, and indeed, neurogenesis has been demonstrated in animal models and to some extent it exists in humans in a few places. For instance, the olfactory bulb, where neurons are responsible for detecting odorants in the environment, for smell, that is. And in a little subregion of the hippocampus, a memory area, there's probably some neurogenesis. But the bulk of really good data out there point to the fact that in humans, there's not much turnover of neurons. What that means is that the neurons you're born with are the ones that you're going to be using most, if not all, of your life. In fact, you're born with many more (laughs) neurons than you'll have later, and there's a process of naturally occurring cell death called apoptosis that occurs during development. So you actually are born with many more neurons than you have later in life, and that's the reflection of a normal, healthy process of nerve cell elimination. So the estimates vary, but anywhere (laughs) from, you know, a third to maybe even a half or even two thirds of neurons, depending on the brain area, just going to die across development. That might sound terrible, but that's actually one of the ways in which you go from being kind of like a little potato bug flopping around helplessly in your crib to being an organism that can walk and talk and articulate and, uh, calculate math, or do whatever it is that you do for a living. So the brain has a set of elements, these nerve cells and other cells, and it needs to use those for the entire lifespan. So having a BBB, a blood-brain barrier around the brain is absolutely critical. The ovaries and testes have a barrier for, we assume, the reason that they contain the genetic material by which we can pass on our genes to our offspring, progeny, meaning make children and those children will have our genes, or at least half of them, the other half from the partner, of course. If the cells within the ovaries and testes are mutated, well, then you can get mutations in offspring, so that's very costly in the evolutionary sense. So it makes sense that you would have a barrier from the blood. So if you ingest what's called a mutagen, if you ingest something that can mutate the genes of, of cells, you can imagine why there would be a premium on not allowing those mutagens to get into the brain, the ovaries, or the testes. Okay? So the brain has this BBB, this blood-brain barrier around it, which makes it very, very hard for substances to pass into the brain unless those substances are very small or those substances and molecules, uh, are re- critically required for brain function. However, there are a couple of regions in the brain that have a fence around them, but that fence is weaker. Okay? It's sort of like going from a really big wall, thick, e- electronic s- 24-hour surveillance fence where nothing can pass through except only the exclusive cargo that's allowed to go through, to having a little cyclone fence with a, you know, couple holes in it, or it's a kind of a picket fence that's falling over and substances can move freely in, from the blood circulating in the body into the brain. And it turns out that the areas of the brain that monitor salt balance and other features of what's happening in the body at the level of what we call osmolarity, at the concentration of salt, reside in these little sets of neurons that sit just on the other side of these weak fences. And the most important and famous of these for the sake of today's conversation is one called OVLT. OVLT stands for the organum vasculosum of the lateral terminalis. It is what's called a circumventricular organ. Why circumventricular? Well, not to bog you down with neuroanatomy, but your brain is a big squishy mass of neurons and other cell types, but it has to be nourished, and through the middle of that brain, there is a tube, there's a hollow that creates spaces, and those spaces are called ventricles. The ventricles are spaces in which cerebral spinal fluid circulates and it nourishes the brain. It does a number of other things as well. The circumventricular organs are areas of the brain that are near that circulating fluid, and that circulating fluid has access to the bloodstream and the bloodstream has access to it, and this structure that I'm referring to, OVLT, organum vasculosum of the lateral terminalis, has neurons that can sense the con- the contents of the blood and to some extent, the cerebral spinal fluid. There are a couple other brain areas that can do this as well. They go also by the name of circumventricular organs, and I'll talk about the names of some of those other areas. But for today, and I think for sake of most of the discussion, understand that the OVLT is special. S- why? Because it doesn't have this thick barrier fence, which sounds like a bad thing, and yet it's a terrific border detector. The neurons in that region are able to pay attention to what's passing through in the bloodstream and can detect, for instance, if the levels of sodium in the bloodstream are too low, if the level of blood pressure in the body is too low or too high, and then the OVLT can send signals to other brain areas, and then those other brain areas can do things like release hormones that can go and act on tissues in what we call the periphery, in the body, and for instance, have the kidneys secrete more urine to get rid of salt that's, excessive salt in the body, or have the kidneys hold on to urine, to hold on to whatever water or fluid that one might need. So before I go any deeper into this pathway, just understand that the OVLT has a very limited barrier. It can detect things in the bloodstream, and this incredible area of the brain almost single-handedly sets off the cascades of things that allow you to regulate your salt balance, which turns out to be absolutely critical, not just for your ability to think and for your neurons to work, but indeed for all of life. If the OVLT doesn't function correctly, you're effectively dead or dead soon. So this is a very important brain region.

Andrew Huberman 24:15 So let's talk about the function of the OVLT and flesh out some of the other...... aspects of its circuitry, of its communication with other brain areas and with the body, in the context of something that we are all familiar with, which is thirst. Have you ever wondered just why you get thirsty? Well, it's because neurons in your OVLT are detecting changes in your bloodstream, which re- detect global changes within your body, and in response to that, your OVLT sets off certain events within your brain and body that make you either want to drink more fluid or to stop drinking fluid. There are two main kinds of thirst. The first one is called osmotic thirst and the second is called hypovolemic thirst. Osmotic thirst has to do with the concentration of salt in your bloodstream. So let's say you ingest something very, very salty. Let's say you ingest, you know, a big bag of... You know, I, I confess I don't eat these very often, but I really like those Kettle potato chips, and they're pretty salty. I've never actually measured how much sodium is in them. I'm sure the information is there. Every once in a while, if I'm particularly interested in doing so, I'll just down a bag of those things, and I really like them, and they're very salty. But they almost always make me feel thirsty, and the reason is that by eating those, I've ingested a lot of sodium. Again, not a frequent occurrence for me, but happens every now and again. And I don't have too much shame about that because I think I have a pretty healthy relationship to food, and I enjoy them, and I understand that it will drive salt levels up in my bloodstream, and that will cause me to be thirsty. But why? Why? Because neurons in the OVLT come in two main varieties. One variety senses the osmolarity of the blood that's getting across that weak little fence that we talked about before, and when the osmolarity, meaning the salt concentration in the blood, is high, it activates these specific neurons in the OVLT, and by activates, I mean it causes them to send electrical potentials, literally send electrical signals to other brain areas, and those other brain areas inspire a number of different downstream events. So what are those other brain areas? Well, the OVLT signals to an area called the supraoptic nucleus. The name and why it's called the supraoptic nucleus is not necessarily important. It also signals to the so-called paraventricular nucleus, another nucleus that sits near the ventricles and can monitor the, uh, qualities, the chemical qualities of the cerebral spinal fluid, as well as probably the bloodstream as well. And the consequence of tho- that communication is that a particular hormone is eventually released from the posterior pituitary. Now, the pituitary is a gland that sits near the roof of your mouth. It releases all sorts of things, like growth hormone and luteinizing hormone. Luteinizing hormone will stimulate things like estrogen and testosterone, uh, production and release from the ovaries and testes and so on. The pituitary has a bunch of different compartments and functions, but what's really cool about the pituitary is that certain regions of the pituitary actually contain the axons, the wires of neurons, and the neurons reside in the brain. And so the supraoptic nucleus gets a signal from the OVLT. The signal is purely in the form of electrical activity. Remember, neurons aren't talking in one another about what's happening out there. They're not saying, "Pss, hey, there's, you know, too much salt in the bloodstream. Let's do something about it." All they receive are, are so-called action potential, waves of electricity. The neurons in the supraoptic nucleus then release their own electrical signals within the pituitary, and some of those neurons and nearby neurons are capable of releasing hormones as well as electrical signals. So from the pituitary, there's a hormonal signal that's released called vasopressin. Vasopressin also goes by the name antidiuretic hormone, and antidiuretic hormone has the capacity to either restrict the amount of urine that we secrete or, when that system is turned off, to increase the amount of urine that we secrete. So there's a complicated set of cascades that's evoked by having high salt concentration in the blood. There's also a complicated set of cascades that are evoked by having low concentrations of sodium in the blood. But the pathway is nonetheless the same. It's OVLT is detecting those osmolarity changes, communicating to the supraoptic nucleus. Supraoptic nucleus is either causing the release of or is releasing vasopressin, antidiuretic hormone, or that system is shut off so that the antidiuretic hormone is not secreted, which would allow urine to flow more freely, right? Antidiuretic means anti-release of urine, and by shutting that off, you are going to cause the release of urine. You're sort of allowing a system to flow, so to speak. The second category of thirst is hypovolemic thirst. Hypovolemic thirst occurs when there's a drop in blood pressure,

Andrew Huberman 29:27 okay? So the OVLT, as I mentioned before, can sense osmolarity based on the fact that it has these neurons that can detect how much salt is in the bloodstream, but the OVLT also harbors neurons that are of the baroreceptor/mechanoreceptor category. Now, more on baroreceptors and mechanoreceptors later, but baroreceptors are essentially a receptor, a... meaning a protein that's in a cell, that responds to changes in blood pressure. So there are a number of things that can cause decreases in blood pressure. Some of those include, for instance, if you lose a lot of blood, right? If you're bleeding quite a lot, or in some cases, if you vomit quite a lot, or if you have extensive diarrhea, or any combination of those. And there are other things that can reduce blood volume, and we will talk about some of those later, but in the classic case of hypovolemic thirst-One is simply losing blood and therefore blood pressure goes down. So very simple to, to imagine in your mind. You have these pipes which are the arteries, veins, and capillaries, and when you lose some blood volume, the pressure in those arteries, veins, and capillaries goes down. OVLT has neurons that can sense that reduction in blood pressure because of the reduc- because of the presence of baroreceptors in OVLT. There are other elements that also play into the response to what we call hypovolemic thirst. For instance, the kidney will secrete something called renin. Renin will activate something called angiotensin II from the lungs, of all things. Amazing. And angiotensin II itself can act on OVLT, organum vasculosum and lateral terminalis, which in turn will create thirst. Okay? So in both cases, right, the osmolarity sensing system, meaning osmotic thirst, and in hypovolemic thirst where blood pressure has dropped, the end result is a desire to drink more. And that desire to drink more comes through a variety of pathways that are both direct and indirect, include vasopressin and don't include vasopressin. But I think for just sake of general example, and even for those of you that don't have any biology background or physiology background, just understand that there are two main types of thirst. Both types of thirst, os- osmotic thirst and hypovolemic thirst, are not just about seeking water, but they also are about seeking salt. In very general terms, salt, AKA sodium, can help retain water. Now that doesn't mean that salt always retains water. If you have excessive amounts of salt, will you retain excessive amounts of water? Well, sort of. As we'll soon learn, it's all contextual. But for most cases, we can say that by having salt in our system, our brain and our body can function normally, provided the levels of salt are adequate and not too high or too low. And thirst, while we often think of it as just a way to bring fluid into our body, is designed as a, kind of a interoceptive perception. What I mean by (laughs) that, interoception as many of you know now from listening to this podcast, is a paying of attention or r- or a recognition rather, a conscious recognition of the events going on within our body. So when we are thirsty, it's a certain form of interoception. We go, "Oh, I, I need something," or, "I crave something." You may not know exactly what you need, but when you are thirsty, you're not just seeking water. You're also seeking to balance your osmolarity, which means you may be seeking salty fluids or foods. In some cases, you'll try and accomplish this by eating. Or it may be that you're trying to avoid or you will be inspired to avoid salty fluids and foods. But if you want to understand sodium and its roles in the body, you have to understand thirst. And if you want to understand thirst, you have to understand how fluid balance is regulated in the body. That's not surprising at all. But sodium and water work together in order to generate what we call thirst. Sodium and water work together in order to either retain water or inspire us to let go of water, to urinate. So

Andrew Huberman 33:47 before we can dive into the specifics around salt and how to use salt for performance and various recommendations and things to avoid, we need to drill a little bit deeper into this fluid balance mechanism in the body. And for that reason, we have to pay at least a little bit of attention to the kidney. The kidney is an incredible organ. And one of the reasons the kidney is so amazing is that it's responsible for both retaining, holding onto, or allowing the release of various substances from the body. Substances like glucose or amino acids, urea, uric acid, salt, potassium, magnesium. It's basically a filter, but it's a very, very intelligent filter. I mean, intelligent meaning it doesn't have its own mind, but the way it works is, is really beautiful. Basically, blood enters the kidney, and it goes through a series of tubes which are arranged into loops. If you want to look more into this, there's the, the beautiful Loop of Henle and other aspects of the kidney design that allow certain substances to be retained and other substances to be released depending on how concentrated those substances are in the blood. The kidney responds to a number of hormonal signals, including vasopressin, in order to, for instance, antidiuretic hormone, in order to hold on to more fluid if that's what your brain and body need. And it responds to other hormonal signals as well. So it's a pretty complex organ. Nonetheless, there's a key point which I already mentioned that I think most people don't realize. This is actually something that I like to tell kids when I meet them, provided that they're of appropriate age. I'll say, uh ... Oftentimes we have kids that learn that I'm a scientist, they'll, they'll ask a, a question about something related to science and, uh, hopefully, uh, for my sake, it's something about neuroscience. Uh, but one thing that I'll tell kids, I'll say, "You know, did you know that your, your urine, your pee, is actually filtered blood?" And occasionally that will really terrify a kid, but, um, that also (laughs) occasionally really terrifies an adult. Uh, but indeed, your urine is filtered blood. Basically blood gets into the kidney, the kidney's going to filter out certain things, certain things are going to be allowed to pass through and others are not. Okay? So the way the kidney is designed is that about 90% of the stuff that's absorbed from the blood is going to be absorbed early in this series of tubes, and only a small percentage is going to be regulated or worked out as you get into what's called the distal kidney. Distal just means the furth- the furthest part away. Okay? The proximal is up close. Um, so like your shoulder is proximal to your midline of your body and your hand is distal. So in biological terms you hear about proximal, distal, which just means near or far from. So just to give a really simple example, let's say that you are very low on fluid. You haven't had much to drink in a while. Maybe you're walking around on a hot day.Chances are that the neurons in your OVLT will sense the increase in osmolarity, right? The concentration of salt is going to be increased relative to the fluid volume that's circulating. This, of course, assumes that you haven't excreted a lot of sodium for one reason or another, but that increase in osmolarity is detected by the OVLT. The OVLT is going to signal a bunch of different cascades through the superoptic nucleus, et cetera, and then vasopressin is going to be released into the bloodstream. And vasopressin, again also called antidiuretic hormone, is going to act on the kidney and change the kidney's function in a couple of different ways, some mechanical, some chemical, okay? In order to make sure that your kidney does not release much water, doesn't make you want to urinate, and in fact, even if you d- would try to urinate, your body's going to tend to hold onto its fluid stores. 'Kay? So very simple straightforward example. We can also give the other example whereby if you're ingesting a lot, a lot, a lot of water, and it's not a particularly hot day, and you're not sweating very much, let's assume your salt intake is constant or is, or is low for whatever reason, well, then the osmolarity, the salt concentration in your blood is going to be lower. Your OVLT will detect that because of these osmo-sensing neurons in your OVLT. Your OVLT will fail to signal to the superoptic nucleus, and there will not be the release of vasopressin antidiuretic hormone, and you can excrete, uh, all the water that, uh, your body wants to excrete, meaning you'll be able to urinate. There's no holding onto water at the level of the kidney. Okay? Very simple examples, but hopefully it illustrates how events within the blood, meaning the concentration of salt relative to the amount of fluid, right? That's what osmolarity is, is detected by the OVLT. The brain then communicates to the pituitary. The pituitary sends a hormone out into the blood, and the hormone acts on the kidney to either hold onto or let go of fluid, meaning to prevent you from wanting to urinate or from stimulating you to want to urinate. Very, very simple kind of yes/no type situation here. There's a lot of nuance to this in reality. There are a lot of other hormones in this pathway, but I think for least this stage of the discussion, this should be sufficient. Some of you may have noticed that a molecule we've

Andrew Huberman 39:08 been talking a lot about today, vasopressin, was also mentioned on a previous episode of the Huberman Lab Podcast, but in a very different context. The molecule I'm referring to is vasopressin, and as I mentioned, it's a hormone involved in antidiuresis, meaning preventing urination. It's an antidiuretic. But we also talked about vasopressin in the context of desire, love, and attachment. We talked about it in the context of monogamy and non-monogamy in a species of animal called the prairie vole. (laughs) You can check out, uh, that episode. I believe, uh, vasopressin and the non-monogamous, uh, prairie voles are, uh, mentioned, uh, in the timestamp, so should be easy to find. Vasopressin is made at multiple locations in the nervous system, mainly the superoptic nucleus, and indeed, it's also involved in aspects of sexual behavior and mating. Now, it does that through mechanisms that are distinct from its antidiuretic effects. In fact, there are people and, uh, who take vasopressin as an aphrodisiac. Now, I'm certainly not suggesting people do that, but I have all the confidence in the world that the moment I talk about vasopressin, someone in the comments is going to say, "What do you think about vasopressin nasal sprays?" and this kind of thing. Vasopressin and, indeed, oxytocin, another, uh, hormone that's involved in pair bonding and various aspects of brain and body function, are available as, uh, nasal sprays, uh, that can get up into the deep recesses of the brain and c-can impact some of these core what we call hypothalamic functions, these primitive drives and hypothalamic functions. I would encourage a lot of caution, um, maybe even extreme caution, in recreational use of things like vasopressin and oxytocin unless you are working with MD... an MD, excuse me, and they prescribe it or they really know what they're doing. These are powerful hormones that have a lot of different effects on the brain and body. The way that vasopressin, meaning antidiuretic hormone, prevents the release of fluid as urine from the body is pretty interesting. It acts directly on the kidney, so as I mentioned before, blood flows into the kidney. A number of things are retained in the early part of the kidney. Vasopressin acts at a fairly distal, meaning kind of, um, end, endgame, uh, part of the, of the loops of tubes through the kidney, and it increases the permeability of those tubes. In other words, it makes sure that the fluid that would otherwise pass into a collecting duct and then go out to the bladder never actually makes it to the bladder. I point this out because what antidiuretic hormone does is it prevents the bladder from filling at all. It's not as if it locks fluid in the bladder and prevents you from urinating. I think the way I've been describing things up until now and the way you'll hear about antidiuretic hormone, it might sound like it kind of locks up the bladder or prevents you from being able to urinate, but you have a full bladder. That would be very uncomfortable. That's not the way it works. It actually causes the tubes headed towards the bladder from the kidney to become permeable, meaning to allow fluid to go back into the bloodstream into the rest of the body, so that fluid never actually fills the bladder, and so you never feel the urge to urinate. Now, this is an episode about salt. A key thing to understand about the kidney is that the kidney uses sodium in order to conserve water, which has everything to do with the fact that sodium can actually hold water. Put differently, water tends to follow sodium, so where we have sodium, we tend to have water, and sodium, when it's concentrated, can hold onto water, and that's one of the main ways that the kidney holds onto water in the body, and as we'll soon learn, it is... there is no simple and direct formula to say, for instance, "Okay, if salt levels are high, a lot of water is retained, and if salt levels are low-A lot of water is released. On the one hand, that can be true, but it's also the case, because these systems are homeostatic, meaning they're always seeking balance, both within system, within the salt system, and between systems, the salt and water system. It's also the case often that if we have enough sodium, well then, we can secrete sodium and some water will follow, or if we don't have enough sodium, then, yes, indeed, because we're not holding on to water, more fluid can be excreted. But if that condition of low sodium lasts long enough, then we start to retain water because the body recognizes, "Ah, salt is low and water is being excreted," and eventually a system will kick in to retain water. So I'd love to give you a simple black and white, yes or no answer for low sodium, high sodium, moderate sodium, and water balance, but it's all contextual. And when I say contextual, I mean it will depend on blood pressure, hypertension, pre-hypertension if that's there, maybe normal tension, hormone levels, exercise, et cetera, et cetera. A pretty good example of how complicated this can all be is one that some of you may be familiar with. It's pretty well-known that during certain phases of the menstrual cycle when estrogen and progesterone and other hormones are fluctuating, that water can be retained in the body. There's, it's what's called edema or, or a swelling sometimes. So the, the common assumption, and indeed it can be true, that when estrogen levels are high, there's water retention in the body. Also in males if estrogen levels are high, there can be water retention in the body. This is one of the reasons why, uh, athletes and in particular bodybuilders who take anabolic steroids like testosterone, which can be converted into estrogens, sometimes they'll look, they'll walk around, they look like they were partially inflated. They look like they're going to pop, and it's, and it's, it looks like a swelling of the skin, not just because they have large muscles. And that's not always, but often water retention due to testosterone conversion into estrogen. Now, that all sounds consistent, right? Estrogen levels fluctuated in the menstrual cycle, in males where there's an increase in estrogen there's retention of water, but actually estrogen acts as a diuretic. So one would think, okay, when estrogen levels go up, there should be a lot of fluid excreted. But I bring up this example to point out that it's a very complicated and dynamic balance between hormones and salt and fluid. You can't draw a one-to-one relationship there, and that turns out to be a very important point, and we can use that not as a way to further complicate things, but as a way to understand under which context less sodium intake or more sodium intake can be beneficial. So that's where I'd like to turn our attention now. So how much salt

Andrew Huberman 45:46 do we need and what can we trust in terms of trying to guide our ingestion of salt? First of all, I want to be very, very clear that there are a number of people out there that have pre-hypertension or hypertension. You need to know if you have pre-hypertension or hypertension. You need to know if you have normal tension, meaning normal blood pressure. Everyone should know their blood pressure. It's an absolutely crucial measurement that has a lot of impact on your immediate and long-term health outcomes. It informs a lot about what you should do. Should you be doing more cardiovascular exercise? Should you be ingesting more or less salt? Should you be adjusting any number of different lifestyle factors? So you need to know that, and without knowing what your blood pressure is, I can't give a, uh, one-size-fits-all recommendation. And indeed, I'm not going to give medical recommendations. I'm simply going to spell out what I know about the research, which hopefully will point you in the direction of figuring out what's right for you in terms of salt and indeed fluid intake. There is a school of thought that everybody is consuming too much salt, and I do want to highlight the fact that there are dozens if not hundreds of quality papers that point to the fact that a, quote-unquote, "high salt diet" can be bad for various organs and tissues in the body, including the brain. It just so happens that because fluid balance, both inside and outside of cells, is crucial, not just for your heart and for your lungs and for your liver and for all the organs of your body, but also for your brain, that if the salt concentration inside of cells in your brain go, becomes too high, neurons suffer. Right? They will draw fluid into those cells because water tends to follow salt, as I mentioned before, and those cells can swell. You can literally get swelling of brain tissue. Conversely, if salt levels are too low inside of cells in any tissue of the body, but in the brain included, then the cells of the body and brain can shrink because water is pulled into the extracellular space away from cells. And indeed under those conditions, brain function can suffer, and indeed the overall health of the brain can suffer. So there are many reports out there indicating both in experimental models and to some extent in humans, that overconsumption of salt is bad for brain function and longevity. And yet there is also decent evidence in both animal models and humans that if salt consumption is too low, then brain health and longevity will suffer, as will other organs and tissues of the body. So like most things in biology, you don't want things too high or too low. Now, I would say that the vast majority of studies out there point to the fact that a high salt diet is detrimental to brain health and function. Most of the studies have focused on that aspect of salt balance and its consequences on brain function.One critical issue with many of those studies, however, is that the high salt diet is often coupled to other elements of diet that are also unhealthy. Things like excessively high levels of carbohydrates or fats, or combinations of carbohydrates and fats. And so, while I know there are many burning questions out there about how much salt one needs if they are on a low carbohydrate diet, or if they are fasting, or if they are on a vegan diet, there haven't, simply not been many studies that have explored the low, moderate, and high salt conditions on a backdrop of very controlled nutrition. And that's probably reflective of the fact that there are not a lot of very well controlled nutrition studies out there. There are some, of course, but it's very hard to get people to adhere to nutritional plans in a very strict way, and to do that for sufficient periods of time that would allow that, the various health outcomes to occur. Nonetheless, there's some interesting reports that indicate that the amount of salt intake can indeed predict health outcomes, or what we call hazardous events. Uh, things like cardiovascular events and stroke and so forth. And what's interesting is that indeed a lower, I'm not saying low, right, because I don't believe that you want your diet to be truly low in anything except perhaps poison. But a lower salt diet can reduce the number of these so-called hazardous events. But it's a somewhat of a shallow U-shaped function such that, yes indeed, a high salt intake can be very detrimental for your health, both in terms of cardiovascular events, stroke, and, and other deleterious health events. But somewhere in the middle that actually sits quite to the right, meaning higher than what is typically recommended for salt intake, can actually reduce the number of these hazardous events. At least some reports point to that. And so I want to emphasize what one of those particular reports says, and I also want to be sure to counter it from the perspective of the context that that study was set in. Because again, my goal here is not to give you a strict re- set of recommendations at all. It's to point you to the literature, try and make that literature as clear as possible, and allow you to evaluate for yourself. And I don't just say that to protect us. I say that to protect you because indeed you are responsible for your health and your health choices. So, the paper that I'm referring to is a very interesting one. We of course never want to put too much weight on any one report, but this is a paper that was published in 2011 in the Journal of the American Medical Association. The title of the, the paper is Urinary Sodium and Potassium Excretion, and the Risk of Cardiovascular Events. We have not talked much about potassium yet. But sodium and potassium tend to work in concert in the brain and body in order to regulate various physiological functions and health, and we'll talk more about potassium as time goes on. The key plot or set of data in this study, um, for those of you that want to look it up, we will link to it, and there are a lot of data in here, uh, but is figure one, which is basically evaluating the amount of urinary excretion of sodium, which is a somewhat indirect, but nonetheless valuable measure of how much sodium people were ingesting. And plotted against that is what they call the hazard ratio, and the hazard ratio points to, um, the composite of cardiovascular death, stroke, myocardial infarction, and an infarct is an injury, and hospitalization for congestive heart failure. And what it points to is the fact that the hazard ratio is lowish at sodium excretion of about two grams per day, but then continues to go down until about 4.5 to 5 grams per day, that, remember this is sodium excretion, so it's reflective of how much sodium was in the body, which is reflective of how much sodium was ingested, and then the hazard ratio increases fairly dramatically, a very s- uh, steep slope, heading anywhere from 7 to 8 to 10 and out towards, you know, 12 grams of sodium excretion per day. So, the simplest way to interpret these data are that at fairly low levels of sodium, meaning at about two grams per day, you run fewer health risks. But the number of risks continues to decline as you move towards four and five grams per day, and then as you increase your salt intake further, then the risk dramatically increases. So, no study is holy, nor is any figure in any study or any collection of studies holy. Rather, we always want to look at what the bulk of data in a particular field reveal. Nonetheless, I think the, the plot that we described, meaning the, the graph that we described is pretty interesting in light of the 2020 to 2025 dietary recommendations for Americans, which are, which is that people consume no more than 2.3 grams, meaning 2,300 milligrams of sodium per day. That's about a half a teaspoon of salt per day. Now most people are probably consuming more than that because of the fact that they are ingesting processed foods, and processed foods tend to have more salt in them than non-processed foods. Now of course, that's not always the case, right? Sea salt is not a processed food in most cases. Um, and there are a lot of unprocessed foods that can be high in sodium. But processed foods in particular tend to have a lot of sodium. You can see this simply by looking at the packaging of any number of different foods. But if we are to take this number of 2.3 grams, that's the re- uh, recommended cutoff for ingestion of sodium, it actually falls in a portion of the-... curve that we were talking about a moment ago, that indeed is associated with low hazard out... Low, low incidence of hazardous outcomes, cardiovascular events, stroke, et cetera. But the ingest- according to that plot, the ingestion of 4 or 5 grams of sodium, almost double or more sodium than is currently recommended is associated with even lower numbers of, of hazardous events. So we need to think about this, and we need to explore it in the context of other studies, of course. And we need to evaluate it in terms of this thing that we've been going back to again and again, which is context, right? These recommendations of 2.3 gram per day cutoff is in the context of a landscape where some people do indeed have hypertension or prehypertension. The incidence of hypertension has gone up dramatically in the last 100 years and seems to continue to go up. Whether or not that's because of increased salt intake or whether or not it's because of increased salt intake and other things, such as like highly processed foods, that isn't clear. Again, pointing to the, the challenge in doing these epidemiological studies and really parsing what aspects of a change in, uh, some health metric is due to, for instance, the ingestion of more sugars versus more salts or simply because of the ingestion of more salts. It's a complicated, almost barbed wire topic by now, but we can start to pull apart that barbed wire tangle and start to evaluate some of the other people and other conditions that exist out there, maybe for you, that actually warrant more sodium intake and where more sodium intake

Andrew Huberman 56:45 might actually be beneficial. So again, I want to be very, very clear that you need to know your blood pressure. If you have high blood pressure or you're prehypertensive, you should be especially cautious about doing anything that increases your blood pressure. And as always, you want to, of course, talk to your doctor about doing anything that could adjust your health in any direction. But nonetheless, there are some important papers that have been published in recent years. I want to point to one of them in particular. This is a paper that was published in the journal, Autonomic Neuroscience: Basic and Clinical, because this paper, like several other papers, ask the question, and indeed they ask the question in the title, it's a review, "Dietary sodium and health: How much is too much for those with orthostatic disorders?" Now, orthostatic disorders come in a bunch of different varieties, and we're going to talk about those in a moment, but there are a number of people out there that have low blood pressure, right? People that g- get dizzy when they stand up, people that are feeling chronically fatigued, and in some cases, not all, those groups can actually benefit from increasing their sodium intake. Several episodes ago on the Huberman Lab Podcast, I gave a, what it's just clearly what we call anecdata, which is not even really data. It's just anecdotal data of an individual who was always feeling hungry and craving sugar, and based on the fact that they also had low blood pressure, I had them talk to a physician, and they got permission to try a little mini experiment on themselves. And so they did, and that mini experiment was anytime they felt like they were craving sugar or they were feeling a little lightheaded and dizzy, rather than reaching for something with caloric intake, they took a little bit of sea salt, a little pinch of sea salt, and put it into some water and drank it, or (laughs) in, uh, the case of this individual, they would actually take a little sea salt packet and they would actually just down a sea salt packet. And for them, that provided tremendous relief for their dizziness, but that, of course, was in the context of somewhat abnormally low blood pressure. So I don't think that they are alone in the fact that many people out there suffer from a low blood pressure condition. Many people out there suffer from a high blood pressure condition. So know your blood pressure and understand that blood pressure, in part, is regulated by your sodium intake and your sodium balance. Why? Well, because of the osmolarity of blood that we talked about before, where if you have a certain concentration of sodium, meaning sufficient sodium in your bloodstream, that will tend to draw water into the bloodstream, and essentially the pipes that are your capillaries, arteries, and, and veins will be full. The blood pressure will get up to your head, whereas some people, their blood pressure is low because the osmolarity of their blood is low, and that can have a number of downstream consequences. I should also mention it can be the consequence itself of challenges or, or even deficits in kidney function, but all of these organs are working together. So the encouragement here is not necessarily to ingest more sodium. It's to know your blood pressure and to address whether or not an increase in sodium intake would actually benefit your blood pressure in a way that could relieve some of the dizziness and other symptoms of things like orthostatic disorders, but of course, to do that in a safe context and to never play games with your blood sugar or your blood osmolarity that could set your system down a cascade of negative events. Let's look at what the current recommendations are for people that suffer from orthostatic disorders, like orthostatic hypo, meaning too low tension, orthostatic hypotension, postural tachycardia syndrome, sometimes referred to as POTS, P-O-T-S, or idiopathic orthostatic tachycardia and syncope. These have these incredibly elaborate names. Those groups are often told to increase their salt intake in order to combat their symptoms. The American Society of Hypertension recommends anywhere from 6,000 to 10,000, these are very high levels, so this is 6 grams to 10 grams of salt per day, keeping in mind again that salt is not the same as sodium, so that equates to about 2,400 to 4,000 milligrams of sodium per day. Again, I, if you want to learn more about this and get more of the citations, I, I'll refer you back to this, uh, study on "Dietary sodium and health: How much is too much for those with orthostatic disorders?" We will put a link to this in the, the caption show notes. So...That's not just in the US. The salt recommendations from the Canadian Cardiovascular Society are 10,000 milligrams of salt per day, so 4 grams of sodium is what that equates to, and on and on and on for things like POTS, for these postural syndromes that result from... Or I should say from the syndromes that involve low blood pressure when people stand up or in certain postures. So I point out this paper and I point out these higher salt recommendations to emphasize again that context is vital, right? That people with high blood pressure are going to need certain amounts of salt intake, people with lower blood pressure and maybe with some of these postural orthostatic syndromes are going to need higher amounts of salt. And for most people out there, you're going to need to evaluate how much salt intake is going to allow your brain and body to function optimally, and there are some fairly straightforward ways to explore that, and there are some ways to explore that in the context of what you already know about thirst and salt appetite that can make that exploration one in which it's not going to be a constant wandering around in the dark, and where you can figure out what's right for you. For most people,

Andrew Huberman 1:02:19 a moderate increase in salt intake is not going to be detrimental provided that you consume enough fluids, in particular water. Okay? Meaning if you happen to overeat salt a bit, you will get thirsty, you will ingest more water, and you will excrete the excess sodium. There is evidence that the body can store sodium in various organs. That storage of sodium may or may not be a detrimental thing. In general, excess storage of sodium in tissues and organs of the brain and body is not thought to be good for long-term health, so eating much more sodium than you need for long periods of time is indeed bad for you. Earlier I mentioned that salt and your hunger and thirst for salt is homeostatically regulated, and indeed that's the case, much like temperature is homeostatically regulated. What that means is, if you pay attention to it, if your salt levels are low, you will tend to crave salt, and salty beverages and salty foods, and in most cases, you should probably follow that craving, provided those salty beverages and salty foods are not bringing in a lot of other things, or anything ideally, that's bad for you. So I think it's fair to say that whether or not you're vegan, vegetarian, carnivore, omnivore, that we should all try to limit our ingestion of processed foods. I... My read of the literature is that, sure, some processed foods are acceptable for us and aren't going to kill us outright, but that for most people in the world, eating fewer processed foods is just going to be a good thing to do. So following your salt hunger and thirst in most cases is going to be beneficial, provided that it's in the context of eating healthy non-processed foods on whatever backdrop of nutritional and dietary recommendations is right for you. I simply can't tell you what to eat and what not to eat, because I acknowledge the fact that some people are vegans because of ethical reasons related to animals, or some people are vegans because of, you know, reasons related to, uh, the climate and, and the environment. Other people, um, do it for specific health reasons. Likewise, I know plenty of people that eat meat and avoid vegetables, believe it or not, and I know people that eat both, and they do this often each... I should say all, citing literature that supports their particular camp and their particular view. It's not a territory I want to get into, but with respect to salt intake and the fact that home- that salt intake is homeostatically regulated, it is the case that if you're craving salt, you probably need it. So for those of you that are sweating excessively, or even if you're in a very hot environment, uh, and you're not exercising and you're just losing, uh, you're losing water and salt from your system, remember also that you can be in a very cold environment, very cold, dry environments often go together, and you can be losing a lot of fluids from your body and you will crave fluids and salt even though it's cold and you're not actually, uh, pers- noticeably perspiring. So if you're exercising a lot, if you're in a particular cold, dry environment, or a particular hot environment, you ought to be ingesting sufficient amounts of salt and fluid. A rule of thumb for exercise-based replenishment of fluid, uh, comes from what I, uh, some episodes back referred to as the Galpin equation. Uh, the Galpin equation, uh, I named it, although, after Andy Galpin, and I think, uh, that is the appropriate attribution there. Um, Andy Galpin is an exercise physiologist at, uh, Cal State Fullerton, I believe, um, and he's going to be a podcast guest here on the Huberman Lab Podcast. He's an exceptional muscle physiologist, he also lives in the practical realm where he gives recommendations about, uh, exercise to expert athletes as well as the everyday person. So the Galpin equation is based on the fact that we lose about one to five pounds of water per hour, which can definitely impact our mental capacity and our physical performance. And the reason that loss of water from our system impacts mental capacity and physical performance has a lot to do with literally the changes in the volume of those cells, the size of those cells, based on how much sodium is contained in or outside those cells, and something that I've alluded to before on the podcast and I'll talk about more, um, in a moment, which is that neurons signal to one another by way of electricity through something called the action potential, and that actually requires sodium and potassium and magnesium. So the Galpin equation suggests that we start exercise hydrated with electrolytes, not just with water. So that means water that has...... some sodium, potassium, and magnesium. They're simple, low-cost ways to do that, we'll talk about. And the formula for hydration, the so-called Galpin equation, is your body weight in pounds divided by 30 equals the ounces of fluid you should drink every 15 minutes. That may turn out to be more fluid than you can comfortably consume during the activity that you're performing. Now, the Galpin equation is mainly designed for exercise, but I think is actually a very good rule of thumb for any time that you need to engage mental capacity, not just physical performance. Uh, your body weight in pounds divided by 30 equals the ama- the ounces of fluid you should drink every 15 minutes. Does not necessarily mean you have to ingest it every 15 minutes on the dot. And I think many activities, physical activities, but also cognitive activities like Zoom meetings, or in-person meetings, or lecturing, or running, or cycling are going to make it complicated to ingest the appropriate amount of fluid every 15 minutes on the dot. I'm not going to speak for Andy, for Dr. Galpin, but I think he would probably agree that these are averages to shoot for, and that unless you're hyperneurotic, the idea is to make sure that you're entering the activity, cognitive or, or physical, sufficiently hydrated, and that throughout that activity, you're hydrating regularly. And it points to the fact that most people are probably under-hydrating, but not just under-hydrating from the perspective of not ingesting enough water, that they're probably not getting enough electrolytes as well, sodium, potassium, and magnesium. So I've said two somewhat contradictory things. On the one hand, I said follow your salt appetite. Follow your salt thirst. If you're craving salt, ingest some salt until you stop craving the salt. On the other hand, I've given you this, um, fairly specific recommendation based on the Galpin equation that you should ingest your body weight in pounds divided by 30. That's how many ounces of fluid you should drink every 15 minutes, which I'm guessing for most people is going to be more fluid than they're currently drinking on average. And so how could it be that you can have a recommendation for what's optimal that's different than the amount that you would reflexively drink? And it has to do with the fact that a lot of the hormone systems like vasopressin, antidiuretic hormone, other hormones like aldosterone, and a lot of the neural and hormonal signals that govern salt and water balance are fairly slow to kick in. So for instance, if you eat a fairly salty meal and you sense that salt, you'll probably, meaning you detect it and perceive it because the food tastes salty, you'll probably want to drink a fair amount of fluid with it. Whereas if some of the salt is disguised by other flavors, something that we'll talk about in a few minutes when we talk about the neural representation of things like salty and sweet, well then, you might not notice that something's salty, and then a few minutes or hours after ingesting that meal, you might feel very, very tired. You might even wonder whether or not, uh, it's because of some blood sugar effect, um, maybe it's a crash in blood sugar you might think, um, or something else related to that meal. Or maybe you think it's because of, you know, some other event in your life, but actually what you, what has happened is you're dehydrated because you didn't recognize that you needed to drink more fluids. So I want to acknowledge the, uh, the contradiction in the idea that everything is homeostatically regulated and therefore you are aware of what you need, and the counterargument that, ah, you need to follow these strict recommendations. It's actually going to be somewhere in between. And of course, your body and brain can start to adapt to certain levels of salt intake. There's now a fairly, um, famous study, uh, that was done in Germany which looked at different phases of salt intake, meaning they had subjects ingest either 12 grams of salt per day or 9 grams per day or 6 grams per day for fairly long periods of time, and they collected urine for testing. This was actually a very controlled study. I'm just going to paraphrase from the, uh, National Institutes of Health, uh, report on this study because, um, they did a very nice writeup of it. Um, and they say that, you know, a big surprise of these results is that whatever the level of salt that was consumed, sodium was stored and released from the subjects' bodies in fairly regular weekly and monthly patterns, meaning people tended to adapt to a certain level of salt intake. And then that led to a fairly constant amount of salt retention and urine fluid excretion, and that's because of the various hormones like aldosterone which regulate sodium excretion from the kidney, and glucocorticoids, which we'll talk about more in a moment, which help regulate metabolism. Glucocorticoids are, uh, released from the adrenal glands which ride atop the kidneys, and there's a very close relationship between the stress system, glucocorticoids, and the salt system. So the, the reason why your salt appetite isn't a perfect readout of how much salt you should ingest and why it might be helpful to follow some of these formulas like the Galpin equation, especially if you're engaging in exercise where you're going to be perspiring, of course, is that your body will tend to adapt to a certain amount of salt intake over time, and then your appetite for salt won't necessarily be the best indication of how much salt you should ingest or avoid. Before I move on, I want to really reemphasize the fact that inside of the Galpin equation, there is that mention of every 15 minutes. And people have come back to me again and again about this saying, "I can't drink that much water every 15 minutes. It's too much, um, volume of fluid in my stomach. I can't run with that," et cetera. Remember, these are averages, so that's what you want to average around a particular activity. These are not strict recommendations where a buzzer goes off and every 15 minutes you have to chug that exact amount of electrolyte-containing solution.Another key feature of the study, uh, that I was referring to before, uh, which incidentally was published in the Journal of Clinical Investigation, is that the body regulates its salt and water balance not just by excreting sodium, right, but by retaining or releasing water. And this is because of the relationship between sodium and water that we were talking about before. And the advantage of this mechanism, they state, here I'm paraphrasing, is that the long-term maintenance of body fluids is dependent, is not as dependent on external water as once believed, right? What the system probably evolved to do was to adjust to different levels of sodium availability in the environment. And that raises a really key

Andrew Huberman 1:14:02 element of salt and its importance in human history and human evolution and human health. We haven't talked too much about this, and there are several very good books about the history of salt. You know, salt was a, was a very valuable and heavily sought after substance throughout much of human history, so much so that there are actually written reports of people being paid for labor in the form of salt. And, you know, salt at, when it's scarce could, uh, has been quite expensive in certain regions of the world, especially regions located further away from the sea. And, uh, a friend of mine who, um, has deep roots within the culinary community told me about traveling to, um, to some somewhat impoverished areas of, of Europe some years ago, and going into homes where in the middle of the kitchen table, there was a, a fish, a salty fish hanging from a thread, uh, above the table. And that because of a lack of availability of table salt, the common practice was to take any food that needed some salt for additional flavoring and to actually rub that food on this salty fish or to squeeze the fish a bit onto, uh, onto the food substance in order to get salt from it. So, you know, that's a very, uh, kind of extreme example. Nowadays, we kind of take salt for granted, and mo- most of the discussion out there is about excess salt, but as I'm pointing out that, you know, salt for a long time has, um, been a very sought after commodity and one that people really cherished for their health. In the episode that I did on metabolism, I talked about the relationship between salt and iodine. If you're interested in iodine and whether or not iodized salt or non-iodized salt is best or required, um, I'd encourage you to listen to that episode, which was about, again, metabolism. Uh, some people may need more iodine intake. Some people perhaps do not. Some people might even want to ingest things like kelp. Some people might not. So, uh, please listen to that episode if you're interested in the iodine aspects of salt, which have direct impact on thyroid hormone and thyroid function, which of course relates to metabolism. Nowadays, there's a lot of interest in and even a kind of proliferation of, uh, what I call fancy salts, so whether or not you should be ingesting sea salts or common, whether or not common table salt will suf- uh, will suffice. In most cases, um, for what we're discussing here, common table salt is fine. Uh, but I should point out that sea salt often contains other minerals which can be very useful, and we will do entire episodes on those other minerals. So sea salt can contain, um, you know, dozens or more of minerals, some of which can be quite valuable to our health, others of which are, are less, less important and only need to be consumed in trace amounts. But you're not going to get many minerals, if any, from common table salt, and that's why in addition to the pretty colors and perhaps some people report that they actually taste better, um, some of these, uh, so-called fancy salts or sea salts, you might want to consume a, uh, more advanced form of salt, if you will. Although, I suppose it's actually the more primitive a form of salt if it's actually the one that comes from the ocean. So we've all heard about how excess salt, it's bad

Andrew Huberman 1:17:13 for blood pressure, can damage the heart, the brain, et cetera. I do want to give some voice to situations where too little salt can actually cause problems, and this has everything to do with the nervous system. So without getting into excessive amounts of detail, the kidneys, as we talked about before, are going to regulate salt and fluid balance. The adrenal glands, which ride atop the kidneys, are going to make glucocorticoids like aldosterone, and those are going to directly impact things like fluid balance, and in part, they do that by regulating how much craving for and tolerance of salty solutions, uh, we have. And, uh, there's some really nice studies that have looked at so-called adrenalectomies. Now, this is an extreme case, and it's typically done in animal models, but it illustrates the role of the adrenals in salt preference. Basically, when the glucocorticoid system, meaning the release of these particular hormones from the adrenal glands, is eliminated by adrenalectomy, -ectomy means removal, then the threshold for what's considered too salty really shifts, okay? So typically, when the adrenals are intact, a animal or a human will prefer a mildly salty to moderately salty solution, if given a choice, and then at some point, it's so salty that it just feels aversive. Uh, just like taking a gulp of seawater is almost always aversive. I can't think of an instance where it's not aversive, and actually drinking seawater can kill you because of the high osmolarity of seawater. You certainly don't want to drink seawater. Under conditions where the adrenals are missing, animals and humans will tend to prefer a higher sodium concentration fluid, and they will be wi- willing to tolerate ingesting very high concentrations of sodium. Now, that's a very crude experiment and not one that you want to do, I promise you. But I mention it because it illustrates the very direct relationship between the stress system, which is the glucocorticoid system, and the salt craving system, and this actually makes sense. Earlier, as we were talking about hypovolemic thirst, when there's a loss of blood pressure from-... usually due to a loss of blood from the body, there is a salt craving in order to bring that blood volume back up, because by ingesting salt you bring fluid into the bloodstream. You're increasing that blood pressure and you can restore the blood that's lost. Now, there are many examples where if sodium levels get too low in the bloodstream, either because people are ingesting too little salt, or they're ingesting too much water and therefore excreting too much salt, that it can cause stress and anxiety. There's some really nice data that point to the fact that low dietary sodium can actually exacerbate anxiety in animal models, and to some extent there's evidence for this in humans as well, and that should not come as a surprise. The whole basis for a relationship between the adrenal system, these glucocorticoids, things like aldosterone, and the craving for sodium, is that the stress system is a generic system designed to deal with various challenges to the organism, to you or to me or to an animal, and those challenges can arrive in many different forms. It can be an infection, it can be famine, it can be lack of water, and so on. But in general, the stress response is one of elevated heart rate, elevated blood pressure, and an ability to maintain movement and resistance to that challenge, 'kay? I've said this before, but I'll emphasize it again. There's this common misperception that stress makes us sick, and indeed if stress lasts too long, it has a number of negative effects on our health, but more often than not, if we're pushing, pushing, pushing, you know, we're studying or taking care of somebody or traveling like crazy, we don't tend to get sick under those conditions, but as soon as we stop, as soon as we reduce our adrenaline output, as soon as we reduce our glucocorticoid output from our adrenals, then we will get sick. That's a very common occurrence, and it's because stress actually activates our immune system in the short term. So I'd like to, um, try and dispel this myth that stress actually suppresses the immune system, at least not in the short term. For long term stress, it's a s- different issue. You don't want long term ongoing stress, especially if several weeks or more. Nonetheless, it makes sense that bringing sodium into the body would be at least one way that we would be wired to counteract or to, uh, resist stressors, right? Stressors being the things on the outside coming at us, so it could be stressful relationships, stressful job situation, uh, in- again, infection and so on. It's clear from a number of studies that if sodium levels are too low, that our ability to meet stress challenges is impaired. Now, that doesn't mean to place your sodium intake cosmically high, but it does point to the fact that if you're feeling anxious, perhaps from low blood pressure, which can also give symptoms of anxiety, as we talked about before, but even if it's independent of low blood pressure, that slightly increasing sodium intake, again, I would encourage people to do this not in the context of processed foods and drinks, (laughs) but ideally in the form of maybe a little bit of, of sea salt and water or salting one's food a little bit more, that that can stabilize blood pressure and one's ability to lean into stressors and challenges. And I say this because I think that most people assume that adding salt is always bad, when in fact that's simply not the case. There are conditions such as when we are under stress challenge when there is a natural craving for more sodium and that natural craving for more sodium is hardwired into us as a way to meet that challenge. So it's hard for me to know whether or not people out there, especially the listeners of this podcast, are getting too much, just enough, or too little sodium, so I can't know that. I'm shouting into a tunnel here. You have to decide how much sodium you're ingesting, but I think that there's some, for most people, especially people who are not hypertensive, pre-hypertensive, there's some wiggle room to explore whether more intake of sodium could actually be beneficial for suppressing some of the anxiety responses that they might feel under conditions of stress. Again, more studies need to be done, and certainly s- more studies in humans need to be done, but the relationship between stress and sodium intake, and the fact that additional sodium intake may be beneficial and indeed is naturally stimulated by stress, shouldn't be necessarily looked at as a pathological event. I know when some people get stressed they crave salty foods. That's actually a hardwired biological phenomenon that you see not just in humans but in animals because this is a very primitive mechanism whereby your body is preparing to meet any additional

Andrew Huberman 1:24:20 challenges and stressors. Now, we can't have a discussion about sodium without having a discussion about the other electrolytes, magnesium and potassium. Magnesium is important enough and an extensive enough topic that we should probably do an entire episode just on magnesium. For purposes of today's discussion, I just will briefly touch on some of the forms of magnesium that we've discussed on the podcast before in different contexts. I want to emphasize that many people are probably getting enough magnesium in their diet that they don't need to supplement magnesium. Some people, however, opt to supplement magnesium in ways that can support them, and there are many different forms of magnesium, and just in very brief passing I'll just say that there is some evidence that you can reduce muscle soreness from exercise by ingestion of magnesium