The Science of Healthy Hair, Hair Loss and How to Regrow Hair

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 discussing hair. Hair is a topic that occupies the minds of many people. There are people that are losing their hair and want to halt or reverse that loss of hair, and today we will talk about all the ways that science has taught us we can slow or even reverse hair loss. I confess that researching today's topic was a particular joy for me, not because I'm obsessed with hair, mine or the hair of others, but because hair turns out to be fascinating from the perspective of cellular biology and stem cells, which is a topic that I've long been interested in and that, for much of my career, I focused on in the context of development. So when your brain and your nervous system develop, it develops from a small batch of cells that turns into many, many trillions of cells, and it does that by cell replication, something that we call the cell cycle, and we'll talk a little bit about this and so-called mitosis today. I promise not to get into too much detail. But what makes hair so very interesting from a biological standpoint is that every hair, every single individual strand of hair, has its own little stem cell niche, meaning its own little pocket down there in the follicle in which specific stem cells give rise to those hairs for different durations of time, depending on the hair, where it is on your body, et cetera. So for instance, the hairs on your head will undergo ongoing growth for four to six or even eight years. So were you to not cut your hair, it would continue to grow. One single hair would continue to grow, I guess we could say all the hairs will continue to grow, for up to eight years. That is very different from, for instance, your eyebrows, which have a much shorter period of hair growth, lasting on the order of months. That's why you don't see people with eyebrows that extend down to their waist. But you can see people with hair out on their head that extends down to their waist if they don't cut it. Now, that discrepancy illustrates for us just how incredible hair follicles and the stem cells that reside within hairs are, and their enormous potential to give rise to these things that we call hairs, which are simply proteins of varying length. So today we are going to address what determines the length of a hair, or rather, what determines how long a hair continues to grow before it ceases growing and eventually falls out. We're going to talk about what regulates those stem cells, what allows them to continue to produce hair or cease producing hair. And as we do that, you will learn all the biology in clear, simple terms, regardless of your background, that will really set the stage for understanding what we'll also talk about, which is how to slow hair loss or halt hair loss entirely, or even reverse hair loss. So we will talk about hormone-related hair loss in both men and women, we will talk about some of the mechanical and stress-related influences on hair loss, and we will talk about the chemical and mechanical approaches to halting and reversing hair loss. Everything from minoxidil to dutasteride to ketoconazole to microneedling to thyroid, estrogen, IGF-1 pathways. Again, all made very clear regardless of whether or not you have a background in biology or not. I will also dispel some of the common myths about balding and hair replacement. If you've heard, for instance, that you inherit your patterns of balding from your mother's father, that is not true, although it is true that you do inherit certain genes that influence whether or not you have a predisposition to balding in particular parts of your head, and believe it or not, even in particular parts of your body. But it is not the case that you can simply find a photo of your mother's father, say, uh, age 50 or age 60 or 75 and determine whether or not you'll have the exact same pattern of hair loss. So that's a myth that I'd like to dispel right here and now, and I will dispel some of the other myths about hair loss, hair replacement, and hair regrowth as

Andrew Huberman 4:13 well. Before 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 Helix Sleep. Helix Sleep makes mattresses and pillows that are the absolute highest quality. Talked many times before on this podcast about the fact that sleep is the foundation of mental health, physical health, and performance. Helix understands that everybody's sleep needs are slightly different, so if you go to their website, you can take a brief quiz, and that quiz will ask you questions such as, "Do you sleep on your back, your side, or your stomach?" Maybe you don't know, which is fine. You can simply answer, "I don't know." Or do you tend to run hot or cold during the night? Helix takes those answers and then matches you to a mattress that's ideal for your sleep needs. So for me, it matched me to the Dusk, D-U-S-K, mattress, and I've been sleeping on a Dusk mattress for over two years now and my sleep has been better than it ever was previously. So if you're interested in upgrading your mattress, go to helixsleep.com/huberman, take their brief two-minute sleep quiz, and they'll match you to a customized mattress for you. You'll also get up to $350 off any mattress order and two free pillows. They have a 10-year warranty, and you get to try out their mattress for 100 nights risk-free. They'll even pick it up for you if you don't love the mattress.... but I think you will. I most certainly love mine. Again, if you're interested, go to helixsleep.com/huberman for up to $350 off and two free pillows. Today's episode is also brought to us by HVMN Ketone IQ. Ketone IQ is a ketone supplement that increases blood ketones. Now, I want to be very clear that I, like most people, have heard of the ketogenic diet, but I, like most people, do not follow a ketogenic diet. That is, I'm not in ketosis. However, most people don't realize that you can still benefit from increasing your blood ketones, which is what HVMN Ketone IQ does. I take Ketone IQ prior to doing really focused cognitive work. So I take it once in the afternoon anytime I'm going to prepare for a podcast or do a podcast, or if I'm going to, uh, do some research or focus on a grant, anything that requires a high level of cognitive demand, and that's because ketones are the brain's preferred use of fuel, even if you're not following a ketogenic diet. I sometimes also use Ketone IQ prior to workouts, either resistance training workouts or endurance workouts such as running. Again, that's because Ketone IQ, by raising blood ketones, is really a brain fuel. If you're interested in trying Ketone IQ, go to HVMN.com and use the code Huberman to get 20% off. Again, that's HVMN.com, and use the code Huberman to get 20% off. Today's episode is also brought to us by ROKA. ROKA makes eyeglasses and sunglasses that were designed with the biology of the visual system in mind. I've spent a lifetime working on the biology of the visual system, and I can tell you that your visual system has to contend with an enormous number of challenges for you to be able to see clearly throughout the day. So for instance, when you go from a shady area to a well-lit area, your brain and eyes have to make a bunch of different adjustments that eyeglasses of the conventional type don't always compensate for. ROKA eyeglasses and sunglasses compensate for those sorts of changes and all the sorts of changes that your visual system has to contend with, so you always see things with crystal clarity. The company was founded by two All-American swimmers from Stanford, and initially, their eyeglasses and sunglasses were designed for sports performance. And indeed, all of their eyeglasses and sunglasses can be used while running, while cycling. They won't slip off your face if you get sweaty. They're extremely lightweight, but they also have an enormous number of varieties of eyeglasses and sunglasses that are designed to be worn at work or to dinner. So they have the sort of classic performance eyeglasses where makes you look like a cyborg, if you like those. They also have more conventional aesthetics that you'd be comfortable wearing pretty much anywhere. If you'd like to try ROKA eyeglasses or sunglasses, you can go to roka.com, that's R-O-K-A dot-com, and enter the code Huberman to save 20% off your first order. Again, that's R-O-K-A dot-com, enter the code Huberman at checkout.

Andrew Huberman 8:04 Okay, let's talk about hair. And in researching this episode, by talking to experts in the biology of hair and the stem cells that exist in all of us that give rise to our hair growth and the pigmentation in our hair, and in talking to experts who understand how to halt and even reverse hair loss, that there's a tremendously interesting biology surrounding hair. But there's also an incredible psychology around hair. In fact, most people who experience even marginal hair loss undergo pretty severe anxiety. Now, I confess, this is not something I can relate to. I am losing my hair in certain places. I'm 47 years old. I've got a couple patches up front where there's very minimal hair. I think that, as we'll later learn in this episode, reflects a higher density of DHT, dihydrotestosterone, um, receptors at that particular location as opposed to elsewhere on my scalp. But keeping my hair is not something that I've fretted about much of my life, and yet, as I was researching this episode, I remembered an anecdote from my childhood where my father told me, uh, and I think it was because I had, was stressing about something, so I was trying to get to sleep, and he said, "Don't stress. Calm down, and here's why. If you stress too much, it can actually make your hair fall out. In fact, I have a cousin who lay down one night stressed and woke up the next morning and all of his hair was on his pillow." And, uh, I'll never forget that story. Uh, I think he was trying to get me to stress less. I, I don't know if that story made me stress less or not. Um, but in any event, I don't know that that story's true. I'm not gonna challenge the authenticity of that story. I didn't have a chance to reach out to my, my father and ask him, um, to verify or not. But as we'll soon learn, it is true that our psychological wellbeing can impact both the coloration, or lack thereof, and the growth rates of our hair. That's a real thing. And the reverse is also true, which is that as hair starts to thin or fall out or change color, many people experience intense anxiety or even depression. This was not something I was really aware of. And perhaps that's just because I've always kept my hair pretty short anyway. I always assumed that if my hair started to really fall out, I'd just shave my head. But that's me, and that's not most people out there. I think most people, um, would loathe to lose their hair, and in fact, given the enormous number, probably up in the high billions of dollars and euros and other, um, currency, of course, that people invest in trying to halt or reverse their hair loss, it's clear that hair is very, very important to people. What we know is that by age 50, approximately 50% of all men and women will have experienced significant enough hair loss that they start to notice it. And a large percentage, up to 85% of those people, will experience some sort of anxiety that leads them to go out and try and either halt or reverse that hair loss. Now, why at age 50? Well, an important point arises from that, which is that the hair loss is not occurring between the 49th and 50th birthday. Hair loss is ongoing from about age 30 to age 50. It's only by age 50, however, that about 50% of people out there start to notice that hair loss, and this is typically because they'll, you know, they'll be in a, a bathroom or looking in a mirror and, um, the lighting will be bright enough that it permeates the, the, the sort of outer boundary of their hair, and they'll notice that their hair is thinning in a particular location. That's usually how the, this sort of thing happens. So again, a-Our psychological states can impact our patterns of hair growth or loss, and, of course, patterns of hair growth, but more typically hair loss and hair graying, can really impact psychological state. So this is a subject that people take intense interest in, and today we're going to talk about how hair normally grows, why it grows at the rate and for the duration that it happens to, and then as we talk about ways to intervene with that hair loss, those biological mechanisms will come up, because they really provide a nice framework for explaining why certain treatments work more or less well, or why certain treatments might have certain side effects or total lack of side effects. It will also highlight a really key theme that will come up several times in today's podcast, which is that there are both mechanical and chemical approaches to slowing and reversing hair loss. Mechanical approaches would be things as simple as massaging the scalp, but mechanical changes to the scalp can cause either hair loss or facilitate hair growth. This is why things like micro-needling are so prominent in the context of trying to reverse hair loss. But again, there are also chemical approaches to trying to halt or reverse hair loss, and this relates to the fact that the hair growth itself is strongly regulated by hormones such as estrogen, thyroid hormone, insulin-like growth factor, and that other hormones, in particular the androgens, so things like testosterone, but mainly its derivatives like dihydrotestosterone, are very much involved in setting the stage for hair growth by controlling how big or small that pool of stem cells that gives rise to hair growth

Andrew Huberman 13:19 is. So if any of the terms I just used are confusing to you, don't worry. I will make all of those very clear in a moment. It's actually all pretty straightforward and simple, and so I'd like to just start by talking about what hair is, how it grows, why it stops growing, and why hair normally falls out. Let's talk about the biology of hair, and in doing so I also want to talk about stem cells. Now keep in mind that when you hear the word stem cells, you probably, like most people, think about the sorts of cells that people are getting injected into their face to get rid of wrinkles or give them new skin or to give them more hair if it's injected in the scalp, or into a joint to repair a joint or a muscle. Those stem cells are what we call exogenous stem cells. Exogenous, meaning from outside the body. The stem cells that we're going to talk about today are so-called endogenous stem cells, cells that we all make that can give rise to other cells, and that's really the definition of a stem cell. Stem cells are present in all of us from the very beginning of life. So when sperm meets egg, that cell, which we think of as the egg, starts to duplicate and incorporates the DNA from the sperm and the egg, of course. Starts to duplicate, and then those cells give rise to more cells and more cells, and the ability of all those cells to replicate and create more cells are because those cells really are stem cells. Now, at some point, we are a completed body plan, as the biologists say. We end up with a brain and a spinal cord and limbs and fingers and livers and guts and all the things that we need in order to be a functioning human being, even though we're a baby at that time. We haven't grown up. We have all the bits that we're going to have for our entire life. At that point, many of the stem cell populations disappear. For instance, past puberty and probably earlier, you don't get many more new brain cells. You get a few, but you don't get many more new brain cells, because the brain doesn't have many stem cell populations, whereas other organs in your body maintain little pockets of stem cells, or m- in some cases, many, many stem cells that can give rise to more and more of that tissue across the lifespan, and hair is one such tissue. So if we take a look at hair, what we find is that indeed there are these things that we call hairs, but there are also stem cells, and those stem cells are actually what give rise to the hairs that we see on the head of our scalp or that we see on the surface of our body. So right off the bat, you should know that every single hair that you have is there because you have a stem cell population that is giving rise to that particular hair. So let's take a step back, or rather, I should say, let's zoom in on one hair and the stem cell population that gives rise to that hair, because in doing so, you're going to learn all the different components that you can tap into if your goal is to halt the loss of hairs or to replace hairs that have already been lost. Okay? So if we were to just zoom in at the level of one hair, what you would find is that that hair has what typically is called a hair root. So that's the portion below the skin. And when we say below the skin, it means that it dives down into a narrow trench, which is in the so-called epidermis, which is this outer layer of skin. It also has a shaft. The shaft is the part that grows out above the skin. So what you see on somebody's head or you see on their, on their arm, or when you see an eyebrow, you're seeing the shaft of the hair. The root, of course, goes below the skin. What most people don't realize, however, is that down at the base of the root, there's actually a little cave, a little pocket. So if you were to look at this, it would look like a little bulb, a little round area with a bunch of stuff in it right below the root, and within that little cave, there are stem cells. There are populations of cells that have the ability to divide, all right? We call this mitosis. It's a process by which cells can actually divide and take DNA with them and then give rise to other cells. We call those cells that, that divide and move out, we call those daughter cells. We call the cells that give rise to them progenitor cells, but they are effectively stem cells that give rise to these what we call daughter cells. Those daughter cells then become the various types of cells that make up the hair. So when you see a hair, you're not seeing something that grows throughout the lifespan. You're seeing something that's going to be born down there in that little cave, then is going to grow. It's actually going to stack up on top of itself, and that's because hairs are made up of a protein called keratin. There are a bunch of different kinds of keratins, depending on what kind of hair you're looking at. But these are little proteins that stack up on top of one another, and they're structured in a way that makes them pretty darn durable. I mean, it, it's possible, of course, to pull a hair out, um, but if you've ever tried to tear a hair, in particular up...... thick hair, like one from the face, or even a one off the, uh, top of your head. It's actually a, a pretty tensile strong little thing, and that's because keratins stack up on top of one another and bind to one another with a r- really strong bond. So what you end up with is a bunch of protein stacked up on top of one another, and that's the actual hair. Okay? So we've got the hair shaft, the hair root, and then we've got the stem cells down there in that pocket that give rise to the various cells that make up the actual hair. We also have down there in that little cave, which by the way, is actually called the hair bulb, if you really want to know the technical name, 'cause it's shaped like a bulb. We have not just stem cells, but we have cells that give rise to the pigment of the hair, th- that create what's called melanin. Now, some people have very blonde hair, very light hair. Some people have darker hair. But everybody, unless they have what's called the albino mutation, where the hairs are truly white, they lack all melanin, and this is a pretty rare condition, although it does happen, most people have some degree of melanin in their hairs, because there are little pockets of melanin-producing cells, melanin's just a protein, that essentially gets injected into the keratin, into the hair, and it gives it its darker color. Now, there are a couple other components about the hair that you need to know about, especially if you're interested in reversing hair loss or reversing graying of hair. One of those components is a little gland. So next to every hair root, within the dermal layer of the skin, so this is below the epidermis, there is a gland called the sebaceous gland. And the sebaceous gland makes oily stuff, and the oily stuff is called sebum. I know the name sort of evokes something kind of gross, but sebum is actually really cool and really important. The sebum gets injected, or seeps rather, into the area right around the hair as the hair starts to approach the surface, where it goes from essentially root to shaft. And the sebum does two things. First of all, it forms a little bit of a seal right at the place where the hair exits the skin, and that seal is very important actually for waterproofing of your skin. So (laughs) we don't often think of ourselves as waterproof, because we are so accustomed to water just landing on our skin and, and, um, rolling off, but that's because of some of the oily properties of our skin. Now, it's also true that our skin is pretty densely packed with cells, but in the absence of sebum, we would not be as waterproof as we are. Now, as I mentioned, sebum has two important properties. The other important property of sebum is that it actually is a strong antibacterial and antimicrobial. Most people don't realize this. The oils of your skin provide a lot of immune boundary so that things don't get into the hair root or the region around it and infect our skin. So sebum, while the name is sort of, um, unattractive, to be honest, is actually performing some essential roles, both for waterproofing and for our immune system function, protecting us from various kinds of infection. We're going to return to sebum later, 'cause it turns out sebum is also very important as it relates to psoriasis and as it relates to some of the fungal components that can cause hair loss. Okay? So we're just going to file that away. There's another important component of the region around hairs, which is the arrector pili muscle. The arrector pili muscle is a, is a muscle that lies diagonally between that bulb portion of the hair or a little bit above it and goes up to the surface of the skin. The arrector pili muscle is a muscle that contracts when we get cold or when we get scared. So if you've ever had goosebumps, that's because the arrector pili muscle contracts, pulling the skin at the surface down around the little hair follicles, or at least where the hairs meet the, the surface of the skin. And so those little bumps are actually where little micro hairs reside, and the dimples between them are the dimples that occur when this arrector pili muscle pulls down. Now, why would this muscle exist? Well, it has a couple of important functions. One of the functions is that when it pulls down, it causes, as the name suggests, the hairs to stand up, maybe not perfectly vertical, but they ... When you hear, "Oh, I was so frightened, my hair stood up on end," and that's because the hairs become erect. They stand up. Now, why would this happen when we get cold? It happens because when the hairs stand up, air can be trapped between those hairs and can actually warm our body. This is not so much the case if you have very light hair on your skin. If you're a very hairy person, this is going to be a more robust aspect of your physiology. And yes, this is why dogs like huskies can go out in the snow and still remain warm. When they get cold, their hairs actually stand up a bit on end because of the contraction of these arrector pili muscles trapping air in there, and then their body warms the hair trapped beneath the hair, and it's sort of like they've got a blanket on made by the interface between the hair, the air, and their skin. So just to recap all the components of hair and the different things around it that are going to be relevant for understanding how to replace hair that's lost, we have the hair itself, which has the shaft that sticks out over the skin, goes a little bit into the skin, but basically sticks out over the skin. We have the root portion, which goes down into the skin, it goes through the epidermis and into the dermis. Then we have this bulb-like region down at the bottom. Down at the bottom of that bulb, we have stem cells that actually give rise to the actual hair, and we have pigmenting cells that pigment that hair. In addition, and this is very important, there are capillaries that go into that bulb region down at the bottom of the hair and that can serve and support the stem cells, the melanin-producing cells, which are called melanocytes. So the melanin-producing cells and the stem cells get a lot of blood flow that allows them to keep providing new hair, or the proteins that make up hair, and the pigment that goes into those hairs, and those little capillaries deliver not just nutrients and things of that sort, but they also deliver oxygen. Because it turns out that the whole process of growing more hair is a very active process. Now, as soon as you hear oxygen and you hear that the growth is an active process-That should cue you to why so many of the stories around how to keep your hair and regrow hair involve statements like, "Don't wear a hat, it'll make your hair fall out." Or, "If you want your hair to grow back, you know, don't wear hats, or massage your scalp, or increase blood flow." Or why some people will, uh, suggest that people take peppermint oil, for instance, or menthol type oils of different kinds and massage them into the scalp, things that make the scalp tingle. Or there will be light therapies designed to, what? To increase blood flow to the scalp. The whole rationale there is that you're trying to increase blood flow to the stem cell and the melanocyte populations that support the hairs and that actually create the hairs. Now, whether or not those approaches work, we'll touch on a little bit later. I'll just give you a little bit of a hint right now, which is that, while no single one of those approaches that I described is known to regrow hair in a very robust way, because of the requirement for oxygen and nutrients, and because it's such an active process for the stem cells and melanocytes to grow and darken the hairs that grow out of your skin, it is true that manipulations or treatments that increase blood flow to those regions can at least slow the loss of hair, or can even extend the duration over which hairs continue to grow. So if you've heard things like, "Don't wear a hat if you want to maintain your hair," or, "Massage your scalp if you want your hair to grow faster," in some sense, that's true, but none of those manipulations on their own is going to robustly enhance the rate of, of your hair growth. Those things are designed to be done in conjunction with some other treatments that have been shown in many, many clinical studies to increase the rate and duration of hair

Andrew Huberman 26:05 growth. So now you have in mind a picture of what's happening at the level of individual hairs, and if you're anything like me, you're probably thinking, "Wow, there's a lot going on down there, just below the surface of the skin." And indeed there is. But really, the things to think about are that stem cell population that actually give rise to the hair proteins, so that actually create the hair, the melanocytes that darken that hair, they give it pigment, that sebaceous gland and the oil sebum that provide some important antimicrobial and other properties to that general region, and that arrector pili muscle. That arrector pili muscle, as I mentioned earlier, is important for creating goosebumps, and it's important for keeping huskies warm in cold environments. But it's doing some other really important things as well, and we'll talk about those as time goes on in this episode. Right now, what I want to do is just talk for a moment about how hairs actually grow and why they grow the way they do. This is extremely important toward understanding hair replacement and slowing hair loss. There are three basic phases of growth of a hair. The first phase is the phase in which the stem cells down in that bulb give rise to the cells that make up the proteins of the hair, so the actual growth of the hair. And keep in mind that the hair is actually growing from the bottom up. Now you might think, "Of course it's growing from the bottom up. Everyone knows that." But a lot of people think that the hair starts growing right at the surface of the skin. That's not the way it works. The hair is actually growing from deep within the root and stacking up, and then eventually extends out across the top of the skin. That growth phase is called the anagen phase, A-N-A-G-E-N. And this, for some people, will ring a bell, because if you've ever been interested in weightlifting, or even if you're an endurance runner, you'll hear about things that are anabolic, that promote growth, so ana, of growth, or catabolic, that promote breakdown. So the first phase of hair growth is called the anagen phase, and it's a period of varying duration depending on which hair on the body we're talking about. So the anagen or the growth phase for hairs on the head, as I mentioned earlier, is anywhere from two to eight years. For most people, it's going to be about six years. What this means is that, if we were to just not cut our hair, just let our hair grow for two to eight years, that hair would eventually grow to a length that it was at its maximum and then would stop growing. So we can say that the anagen phase of hairs on the scalp is two to eight years, right? The gro- the duration of the growth phase. Contrast that, for instance, with the duration of the anagen phase for hairs of the eyebrows. The hairs of the eyebrows grow about 4.2 millimeters per month. Believe it or not, people have measured this sort of thing. Now, that's an average, so some people are going to have eyebrows that, um, grow much longer per month. Um, I'm somebody who, for instance, has, uh, mostly the same length, uh, eyebrow hairs, but every once in a while, I'll get one of those eyebrow hairs that, like, really seems to be heading off my head, it, like, really wants out of there and so it's much longer than the rest. What does that mean? Does it mean that it grew faster? Maybe, but chances are, the stem cell population in that particular eyebrow follicle, for that one eyebrow hair, is longer than it is for the others. This is really important. I'm trying to illustrate two principles at once here. The first principle is that different hairs on your body, including the hairs on your scalp, have a growth phase of different duration. This is why the hairs on your head can grow very, very long, 'cause they have a very long anagen or growth phase, and the hairs on your eyebrows will only grow for a few months before they actually fall out and then have to undergo replication of the stem cells to give you new eyebrow hair to then grow. What's important here is not just that there are differences in the duration of the growth phase, but rather that the rate of hair growth is not something that tends to differ within a given body region. Right? You'll hear people say, "Oh, my hair grows really, really fast." Other people will say, "Oh, my hair grows really, really slowly."... that is probably not the case. While there could be slight differences in the rate of growth, that is the addition of more keratin to the actual hairs, so creation of more hair more quickly, almost certainly what's happening is that the duration of the anagen phase in some people is just much longer than it is in other people. And we don't realize this, and we tend to think more in terms of how fast hair grows. Because if you were to just look at somebody's hair, you'd say, "Oh, you know, they're all more or less the same length." I mean, some people's bangs are shorter than the back because they cut them, but if they were to just grow their hair, you'd say, "Oh, it's all more or less the same length." But if we were to zoom in with a microscope, we would see that there are a lot of hairs down there in between the other hairs that are very, very short or even tiny, tiny, tiny, and those are coming in as the other ones are finishing their anagen phase. Okay? So that's the anagen or growth phase. After the anagen phase comes the catagen phase. Again, this resembles the word catabolic or the breakdown phase. During the catagen phase, the hair is actually receding not from the top down to the skin surface and then into the root, but the other way. It's actually receding from that bulb region up toward the surface, and that catagen phase is going to also be of different duration depending on which area of the body you're in, and it will vary d- a little bit depending on who you are, meaning from person to person. We'll talk about the influences on the anagen and catagen phase in a moment. Why is it important that it actually recedes from the inside out? Well, that's important because as it does that, there's actually a change in that bulb region down below because normally there's an interface, there's a, a conversation that's occurring between the stem cell population, the melanocytes, and the hair itself, and they support each other. And remember, there's blood vessels going into that area, or rather capillaries that are feeding that area as well. After the catagen phase comes the telogen phase, which means rest. The telogen phase is a period in which no new hair proteins are being added by those stem cells. And during that telogen phase, that bulb down there at the bottom, instead of being nice and oval and, and, um, really having a lot of space in it with all these different things like stem cells, starts to pinch off from the r- from the little tube that comes down from the surface of the skin that normally would have a hair in it. It starts to pinch off, and at some point, many hair follicles pinch off that bulb region, and it recedes and dies. And when it recedes and dies, the stem cell population and the melanocytes go with it. In other words, there is no longer a population of stem cells to give rise to more hair after that telogen phase, and there's no longer melanocytes to pigment the hair, and in fact, the hair isn't there anymore, so there's no hair even to pigment after that telogen phase unless it's a hair of a particular type, such as the hair on your scalp, which can then re-enter the cell cycle and get back into an anagen phase and regrow more hair from stem cells. Okay? So there are three critical stages of the life cycle of a hair that are relevant to today's conversation. There's the anagen phase during which the hair grows, there's the catagen phase during which the hair actually starts to recede and die, right? The protein's actually disappearing from the bottom up. And then we have the telogen phase, which is the phase in which the stem cell population is what's called semiquiescent, semi-quiet, or completely quiescent, where it's not active at all. Those three phases make up the life cycle of a hair, keeping in mind that for some hairs, they can re-enter the life cycle and go back into the anagen phase if there's stem cells there, and if there is oxygen there, and if there is sufficient blood support, and, and this is a very important and, if there are the appropriate hormonal signals to support growth, and there is a reduction or an absence in the hormone signals that actually trigger that telogen phase. I make this point now because much of the rest of today's discussion is going to focus on why particular hormones, such as dihydrotestosterone, cause hair loss, and why inhibiting things like dihydrotestosterone can support the preservation of hair that you have and the regrowth of hair. To make a long story very short, and then we'll get into some additional details that are relevant that I hope you'll stick around to listen to, dihydrotestosterone, which is a derivative t- of testosterone, causes changes in that bulb region where the stem cells reside. It shortens or halts the anagen phase of hair growth, and it extends and promotes the catagen and telogen phase. So when we hear that, oh, you know, dihydrotestosterone makes your hair fall out, or estrogen makes your hair grow, there are real chemical, or we should say biochemical, legitimate reasons as to why that is, but it all comes back to this three phases of hair growth, the anagen growth phase, the catagen, catabolic or hair loss phase, and the telogen phase, which is a rest period in which the, uh, hairs can either come back if it re-enters the anagen phase, or maybe it's over for good. Hormones are the accelerator and the brake on each one of those

Andrew Huberman 35:40 phases. I'd like to take a quick break and acknowledge one of our sponsors, Athletic Greens. Athletic Greens, now called AG1, is a vitamin mineral probiotic drink that covers all of your foundational nutritional needs. I've been taking Athletic Greens since 2012, so I'm delighted that they're sponsoring the podcast. The reason I started taking Athletic Greens and the reason I still take Athletic Greens once or usually twice a day is that it gets me the probiotics that I need for gut health. Our gut is very important. It's populated by, uh, gut microbiota that communicate with the brain, the immune system, and basically all the biological systems of our body to strongly impact our immediate and long-term health, and those probiotics in Athletic Greens are optimal and vital for microbiotic health. In addition, Athletic Greens contains a number of adaptogens, vitamins, and minerals that make sure that all of my foundational nutritional needs are met, and...It tastes great. If you'd like to try Athletic Greens, you can go to athleticgreens.com/huberman, and they'll give you five free travel packs that make it really easy to mix up Athletic Greens while you're on the road, in the car, on the plane, et cetera, and they'll give you a year's supply of vitamin D3 K2. Again, that's athleticgreens.com/huberman to get the five free travel packs and the year's supply of vitamin D3 K2.

Andrew Huberman 36:55 So, now you have in mind the anatomy of the hair and the area from which it grows and the stem cells, et cetera, the fact that there's capillary enervation delivering oxygen and blood flow to the stem cells that give rise to the hair, and that there are these three critical phases of hair growth, anagen, catagen, and telogen. Now let's talk about the accelerators on hair growth and the brakes on hair growth. There are many accelerators on hair growth, but the first one that I really want to underscore is blood flow itself, which equates to the delivery of nutrients and oxygen. This is very important, and it explains a lot of the treatments for halting and reversing hair loss. For instance, one of the longest-standing treatments for halting and reversing hair loss is so-called minoxidil. Minoxidil, sometimes also referred to by the brand name Rogaine, was actually a drug that was developed to treat hypertension. So this is a cardiac drug that lowers blood pressure, and it does that by causing vasodilation. It allows more blood flow not just to the hairs on your scalp, but to hairs everywhere on your body, and indeed, most people don't realize this, but minoxidil won't just slow the loss of hair from your scalp, it is also effective at slowing the loss of hair elsewhere in your body. How does it do that? Well, you now know one of the major ways it does that. It does that by extending the anagen phase, so it basically makes that phase a bit longer. It doesn't make it much, much longer, which is why for most people who are losing their hair quickly or who have already lost their hair, minoxidil alone is not going to be a sufficient treatment. However, minoxidil has been shown to be effective at slowing rates of hair loss in people that are starting to experience some hair loss. I'll get into dosages and things of that sort a little bit later, but right now, I just want to really focus on the logic of why people would take this drug, which is lowering hypertension, at all, as it relates to hair loss, right? That might seem like, kind of crazy until you understand the anatomy and the growth of hairs, which you now do. So that's what minoxidil is doing. It's creating more blood flow to the hairs, which, because minoxidil does have this positive effect, at least most people would like to slow their rates of hair loss on their scalp anyway, it tells you that blood flow and delivery of oxygen and other nutrients from the blood is pretty critical, if not very critical, for the support of the hair growth cycle itself. Now, again, we haven't talked at all about the sorts of chemicals or the signals within the body, such as hormones, that actually direct the growth of hairs. Here, we're just talking about a mechanical change allow more blood flow to the region and thereby extend the anagen phase, which is exactly what happens with minoxidil. Now, minoxidil does have other effects, and this is why dosing of minoxidil becomes a little bit complicated and can be a little bit tricky to troubleshoot. It can greatly lower blood pressure or lower blood pressure just a little bit, depending on how sensitive somebody is to that particular drug. So oftentimes physicians will start people on minoxidil dosages that are very low, ideally that would be the case, and then ratchet it up in order to figure out where the minimal effective dose or the kind of critical threshold is beyond which they start experiencing some pretty uncomfortable side effects, such as, you know, swelling of the ankles or headaches or dizziness. These things can happen with the use of Rogaine, AKA minoxidil. Now, minoxidil has also been associated with increases in the hormone prolactin. Prolactin is a hormone that's released from the pituitary. It is a hormone that acts also as a bit of a neurotransmitter, like many hormones, and it tends to be antagonistic or in opposite to dopamine. So dopamine is a neurochemical, well, it's actually a neuromodulator, meaning it modulates the activity of a bunch of neural circuits in the brain. It also controls the release of various hormones in the body. Dopamine is almost always associated with states of motivation, pursuit, and drive. It has a little bit of a, kind of feelgood element to it, which is why a lot of people think dopamine is associated w- with reward and pleasure, but it's really about energy, motivation, and drive. Dopamine and prolactin are, as I mentioned before, antagonistic to one another. They're in sort of a push-pull. So people who take minoxidil, especially if they're very sensitive to it or they take dosages that are too high, will experience increases in prolactin that in turn can cause things like reductions in libido, reductions in overall feelings of well-being, apathy, and in some cases where the elevations in prolactin are more extreme, they can experience, uh, for instance, increase in male breast tissue, gynecomastia, or even small bits of milk letdown, things of that sort. In women who take minoxidil, the side effects are much like the ones in, experienced in men. So there can be swelling, edema of the tissues, um, because if you get too much vasodilation and too, too much lowering of blood pressure, that's not good. Headaches, dizziness, and so on. So dosing of minoxidil is really important. If somebody's going to use minoxidil in order to try and slow or reverse hair loss, and again, it mainly is going to be used to slow rates of hair loss, not to actually reverse hair loss, the really key thing is to get that dosage right. So the ranges of minoxidil that you'll see suggested and that people use out there are vast. And I should also mention that there are two major routes by which people get minoxidil to the hair follicle. One is to take it systemically as a pill, where it goes into the general circulation. The other is to take it topically as a cream. There are prescription and non-prescription forms of minoxidil, just to further complicate things. But the ranges of oral minoxidil that you'll see out there and that people take range anywhere from 0.25 milligrams all the way up to five milligrams per day. So that's an enormous range. That's like a 20-fold range.... that topical minoxidil is also found in various concentrations, the typical concentration is going to be a 5% concentration that people will use once per day. Topical treatment with minoxidil at 5% concentration is thought to just stay at the scalp, but we now know that it can go systemically, it can get into the general bloodstream. Why that is should make complete sense to you because when you put something on your scalp, I've already told you these little pits, um, these little tubes that go down to those bulb regions, uh, below (laughs) the skin that have direct access to the blood supply, so when you massage something into your scalp, it not only has the opportunity to get into your general circulation, it often does. Especially if it's something that's very water soluble and that way can get into the capillaries and into the general bloodstream. Although topical treatments of which we're going to discuss a number of them today don't tend to get into the general circulation as robustly as taking something by way of pill or capsule. Okay, so minoxidil works by way of increasing blood flow to the stem cell niche below the hair. The dosage ranges of the oral minoxidil are tremendous, .25 milligrams all the way up to 5 milligrams once per day. The dosage range of the topical solutions tends to be a little bit more confined, typically it's a 5% solution, and it's recommended that people use it one time daily, maybe twice daily. It's also important, by the way, if you're going to take this route, that you actually leave that solution on the scalp for three to five minutes. This is important and should make complete sense as to why it's important, you can't just rub the stuff into your head and then rinse it off and expect it to be absorbed, it actually needs to seep down into those hair follicles and access the niche. How do people arrive at the correct dosage for minoxidil? Well, for better or for worse really, in some cases it's accomplished by finding out that you have an unwanted side effect like dizziness or swelling of your ankles or edema, or, um, I would hope this wouldn't be the case but something that suggests there's hyperprolactinemia, you could get a blood test to measure your prolactin or you perhaps notice a drop in libido or some lethargy, uh, these sorts of things that are common to reduce levels of dopamine, increase levels of prolactin. I would hope that if people are working with a physician or if they're not in taking minoxidil that they would start with the lowest possible dose. So for oral minoxidil that would be .25 milligrams and then increase it as needed rather than jumping in right at 5 milligrams, because some of those side effects, uh, in particular the fluid retention and the hyperprolactinemia can be pretty uncomfortable and can disrupt a lot of aspects of life that most all of us consider desirable.

Andrew Huberman 45:37 Okay, so we're really focusing right now on treatments that relate to the critical requirement for hair stem cells to receive blood flow in order to receive oxygen and nutrients to get the hair to grow, and that's really what minoxidil is about. It's also what all of those anecdotes you hear are all about, like massaging the scalp or putting red light on the scalp, although red light might do some other things. In general, heating or lighting of the scalp or massaging of the scalp is really designed to increase blood flow to the scalp. Now, the reason minoxidil works at all is because it is going to increase blood flow around the clock, and that's because people are taking it topically and it's seeping into the general circulation, or at least it's staying s- somewhat restricted to the hair cell niche, or they're taking it orally and it makes it to that hair cell niche, uh, below the follicle. When we massage our scalp however, that's a transient thing, you know, I can massage my scalp right now, I'm no doubt, um, increasing blood flow to certain areas, I'm probably decreasing blood flow to the areas I'm pushing down on, but it's all temporary. I don't know many people that can massage their scalp enough during the day or long enough during the day rather that it would sufficiently increase blood flow. With that said, it is clear that increasing blood flow to the scalp by way of reducing hypertension, which is effectively accomplished by broadening, by expanding the blood vessels and capillaries, is an effective way to at least hold on to the hair that you have. Is it going to completely halt hair loss if you have a strong genetic bias towards hair loss? No. Is it going to reverse hair loss? Very unlikely that it will, but it can slow hair loss or even maintain the hair that you have. So if we were to take a step back and ask ourselves what other sorts of drug treatments are out there besides minoxidil that increase blood flow and that might increase the rates of hair growth or more likely increase maintenance of hair that one already has by increasing blood flow to the niche? And nowadays there are more and more doctors who are familiar with this requirement for blood flow, understand the mechanisms by which minoxidil works, and understand the vast desire out there for people to hold on to the hair they have and regrow hair and they're prescribing things like low dose tadalafil, so 2.5 milligram to 5 milligram tadalafil. Tadalafil was initially discovered as a drug to treat prostate health, it was a drug that we now know can increase blood flow to the prostate and thereby offset some of the issues associated with an aging prostate. Higher doses of tadalafil, sometimes also referred to as the, by its brand name which is Cialis, are used to treat erectile dysfunction, but at the dosages that are used to increase blood flow to the prostate and that now a number of doctors are using to increase blood flow not just to the prostate but to all regions of the body, including the scalp such as 2.5 to 5 milligrams tadalafil. So this is something that I think deserves attention because it falls under the umbrella of increasing blood flow to the hair stem cell niche in order to maintain hair. It is not something that most doctors are going to be familiar with as the way to reverse hair loss because it won't do that, but the use of low dose tadalafil to slow rates of hair loss is...... very much in a logical, mechanistic sense, exactly the same as the logic of using minoxidil to slow rates of hair loss. It's all about increasing blood flow to support the stem cell niche below the hair follicle. The critical requirement for blood flow, oxygen, and nutrients to the stem cell niche is also why you hear a lot nowadays about the use of PRP, platelet-rich plasma, for trying to offset hair loss or even reverse hair loss. We're going to do an entire episode about PRP. It is pretty controversial in certain circles and well-accepted in other circles. A couple of key things to understand about PRP. First of all, it is being used in multiple tissues for different purposes in different clinics. So for instance, board certified physicians in the United States, Canada and Europe are doing PRP injections into ovaries to try and expand the number of healthy follicles and eggs so that people can conceive later in life, or even earlier in life if they don't have any follicles. People are getting PRP injections into their joints in order to try and support joint health. People are getting PRP injections into just about every tissue you can think of. However, PRP, despite what you may have heard, is not stem cells. Somebody tells you they're injecting stem cells, they're either outside the US, Canada, or Northern Europe, or they're injecting something else. So you want to, uh, really look into that. Uh, the safety issues there are the subject totally deserving of an entire episode. I'm not necessarily opposed to the, uh, future of stem cells as a treatment, but keep in mind that stem cells are cells that can give rise to lots of other cell types, and they are cells that divide and replicate, and there's a name for that when it happens in the adult body when you don't want that, and that's called cancer. Tumors are overproduction of cells from stem cells when those stem cells ordinarily should be quiescent. Okay? So keep in mind the difference between stem cells and PRP. PRP, platelet-rich plasma, again, is legal in the US and many other places because it involves drawing somebody's blood, spinning it down at a particular speed which separates out different components within the blood, then taking the platelets and re-injecting those in a solution back into the person's body. So platelet-rich plasma, or PRP, is platelet-enriched plasma from that person. But the basis of PRP is really to encourage nutrient delivery to a particular region in the body using somebody's own platelets, because those platelets are enriched for various nutrients. So people are getting PRP injections into their scalp, those are not stem cell injections, those are PRP injections into the scalp, with some moderate success. These are very expensive treatments. They tend to be transiently successful. I'm sure there are people out there who are going to say, "PRP worked fabulously well for me." That might be the case. I'm not going to dispute that and I'm happy for you, although there are not sufficient clinical data to suggest PRP as a treatment right now, especially given the cost, many thousands of dollars, many, many treatments. It's also the case that the PRP injections, when they work, might work for reasons independent of the platelets. What do I mean by that? Well, soon we're going to talk about a different type of treatment, which is a mechanical manipulation of the hair follicle, typically on the scalp, 'cause that's typically where people want to re-grow hair. I don't know many people who are trying to maintain or, um, accelerate or re-grow their back hair, for instance. They might be out there, but, uh, I don't think there are a lot of them. Or their leg hair, uh, for that matter. Almost always it's going to be scalp hair. And one way that people are doing that is through mechanical stimulation of the hair follicle and the stem cell niche using what's called micro-needling. Micro-needling, as the name suggests, is taking a bunch of little needles, either in a little stamp, so a little square, or nowadays typically it's a roller, (laughs) so it looks like a, a paint roller, except it's, um, got tons of little needles in rows all over that roller. Those needles range in length from half a millimeter to 2.5 mil- millimeters, okay? Millimeters. And one rolls that over the scalp, and if you're thinking, "Ouch, that probably hurts," indeed, it can hurt a little bit or a lot, depending on the thickness and the length of those needles. Micro-needling has been shown to do two things. It has been shown to reactivate semi-quiescent populations of stem cells that are in that telogen phase, putting them back in anagen phase, and thereby stimulate more hair growth. It has also, and this is I think the best use of micro-needling, it has also been shown to be a very effective augment for some of the hormone-based hair re-growth tools and pharmacology that we're going to talk about in a few minutes. So micro-needling and PRP have something very critical in common, which is the needle. The actual injection into the skin. And for those of you that are hearing this and thinking, "Why would disrupting the skin with needles actually support hair growth or regrowth? Wouldn't that just damage the follicle?" Well, this gets into some of the, um, I think interesting, if not fascinating, aspects of our biology, which is that all of the cells in our body really can respond to both chemical and mechanical cues, and when we hear "needle injected into skin," we think, "Oh, that must just be damaging everything, causing all sorts of inflammation." But it turns out that low levels of inflammation caused by things like micro-needling or PRP injections, or even the introduction of any kind of fluid, right, for instance, saline fluid injected into a region, can cause changes in the cells in that region, causing, for instance, stem cell populations that were waning to reactivate again, causing telogen phase follicles that have melanocytes and stem cells that are dying off but not completely gone to re-enter the cell cycle. So micro-needling procedures, PRP injections, things like minoxidil, they all kind of center around this-... same general theme of increasing blood flow, increasing oxygen, delivery of nutrients, or in the case of micro-needling, increasing inflammation just enough at that local site that certain cascades of biological function that relate to proliferation of stem cells or maintenance of stem cell populations are kicked off. Sort of like reminding the cells in that area that they need to stay alive in order to replenish whatever is lost. So sometimes a wound can actually induce some healing, although I do want to point out that the micro part of micro-needling is absolutely key, and this should be obvious to you when you think about scars. I don't know about you, but I've never seen a scar with hair growing out of it. Or if there was, it was probably like one hair. But if you've ever seen a scar, if someone had their appendix out or if someone had a brain surgery, you see that scar because there is no hair growing out of it. So the micro portion of micro-needling is extremely important. We are not talking about causing significant damage to a tissue in order to activate that stem cell population. We're talking about causing micro-damage and micro-levels of inflammation to stimulate

Andrew Huberman 56:10 growth. For those of you that are interested in using micro-needling or micro-needling in combination with chemical treatments like minoxidil or some of the other treatments we'll talk about in a little bit, like finasteride and caffeine, yes, believe it or not, caffeine is being used to regrow hair. Very interesting. Get into that in a moment. But if you're interested in using micro-needling alone or in combination with some of these other treatments, there's a wonderful review that was just published just last year, wonderful because it's very comprehensive, not so wonderful, not to the fault of the authors, because most of the studies out there on micro-needling are not superb. There are ways of gauging the strength of a study, mainly related to their duration, whether or not there were control groups, et cetera. But the review itself is excellent, and the title of the review is Micro-Needling and Its Use in Hair Loss Disorders: A Systematic Review. We will provide a link to this in the show note captions. And this review did a very good job of highlighting both the strengths and drawbacks of the various studies looking at micro-needling. It also explored the use of micro-needling in both men and women and of various ages, and it does appear to be the case that micro-needling shows some positive benefit in both men and women regardless of age, especially when used in combination with the various other treatments that we're talking about. I was also able to glean from this review and some of the papers described within it that needle lengths of about 1 millimeter to 2.5 millimeters seem to be more effective than shorter needle lengths. So if you're scared of the needles and the needle lengths, keep in mind that done properly, micro-needling shouldn't be too painful. Some people experience a little bit more pain than others, but it's not considered a very painful procedure. It is, however, a procedure that can cause some bleeding of the scalp, and that bleeding of the scalp can be very apparent, especially if it's in the front of the head as opposed to on the top of the head and hidden by some hair or if you're already, uh, quite bald in a given region. Uh, so keep that in mind. Um, I suppose one could wear a hat or a wig or something of that sort if they were really self-conscious about it. But the micro-needling itself is causing a physical disruption to the scalp, some degree of bleeding, inflammation, and again, all of that is part of the process by which micro-needling can actually improve hair growth. And of course, there's healing that occurs of the bleeding and the damage to the follicle. This is a transient thing, but understanding the cosmetic implications in the short term as well as in the long term is certainly worth knowing. One thing that's very clear is that the combination of micro-needling and minoxidil treatment together is far more effective than either of those treatments alone. In addition, the combination of micro-needling and minoxidil has been shown to be effective in recovering what are called dead zones. So these are regions of the scalp that are either completely bald or mostly bald for which there is essentially no stem cell population there, and the combination of minoxidil plus micro-needling is somehow able to recover those stem cell populations and allow new hair to grow, although the growth of that hair in those dead zone regions can take a very long time, 30 to even 50 weeks. Neither minoxidil treatment alone nor micro-needling alone has been shown to be effective in recovering these so-called dead zones when those treatments are done separately. So this, I would say, is a strong reason to consider combining micro-needling and minoxidil as opposed to just doing minoxidil or just micro-needling. I should also mention that minoxidil treatment, if you pursue it, is likely something that you are going to have to do for the rest of your life if you want to hold onto the hair growth that you obtain with minoxidil or if you want to maintain the hair that you are already maintaining with minoxidil. Some people have been successful in taking minoxidil, maintaining some hair growth or even stimulating some hair growth, and then coming off minoxidil, but most everyone who goes on minoxidil has to stay on minoxidil because when they cease taking minoxidil, even if they're doing other treatments, they lose the hair that they gained with minoxidil. So that is an important consideration. The decision to go on minoxidil is likely a decision to be on minoxidil for the rest of your life.

Andrew Huberman 1:00:13 I'd like to just take a brief break and thank one of our sponsors, which is LMNT. LMNT is an electrolyte drink that has everything you need and nothing you don't. That means plenty of salt, sodium, magnesium, and potassium, the so-called electrolytes, and no sugar. Now, salt, magnesium, and potassium are critical to the function of all the cells in your body, in particular, to the function of your nerve cells, also called neurons. And we now know that even slight reductions in electrolyte concentrations or dehydration of the body can lead to deficits in cognitive and physical performance. LMNT contains a science-backed electrolyte ratio of 1,000 milligrams, that's one gram, of sodium, 200 milligrams of potassium, and 60 milligrams of magnesium. I typically drink LMNT first thing in the morning when I wake up in order to hydrate my body and make sure I have enough electrolytes and while I do any kind of physical training and after physical training as well, especially if I've been sweating a lot, and certainly I drink LMNT in my water when I'm in the sauna and after going in the sauna because that causes quite a lot of sweating. If you'd like to try LMNT, you can go to DrinkLMNT, that's L-M-N-T.com/huberman, to claim a free LMNT sample pack with your purchase. Again, that's Drink LMNT, L-M-N-T.com/huberman.So

Andrew Huberman 1:01:25 as you're probably starting to realize, there's a relationship between mechanical stimulation of the follicle and blood flow, both of which turn out to be critical for maintaining hair and for stimulating hair growth. Not surprisingly then, an increasingly common treatment for hair loss is Botox. Botox is the brand name for what is otherwise known as botulinum neurotoxin. What is botulinum neurotoxin? Well, botulinum neurotoxin, sometimes just called botulinum for short, is a toxin that's a bacterial toxin that serves to cut the protein that leads to synaptic vesicle release. What in the world did I just say? Well, when your nerve cells communicate with one another, they do that by way of electricity, but the electricity within those nerve cells, those neurons, triggers the release of chemicals from neurons into the synapse, the little gap between neurons, and the release of those chemicals allows the next neuron to be chemically active or, in some cases, it will suppress the electrical activity of that next neuron. Botulinum neurotoxin serves to cut a protein present in neurons, so that neurons cannot release the chemicals that cause other neurons to be active. So this actually is pretty serious. If you were to get botulinum neurotoxin injected into your muscle, you would be paralyzed because the nerves that control contraction of the muscles would not be able to control the release of that chemical onto the muscle which makes it contract. Now, botulinum neurotoxin is commonly used in what's called Botox. Botox is something most people are familiar with because people get it injected in and around their wrinkles, because many wrinkles are triggered by not just loss of tensile strength in the skin, but rather the nerves around the skin and in the skin are hyper-contracted which causes wrinkles. So for instance, I have crow's feet, I like to think that's because I've laughed a lot and smiled a lot, and it's probably also because I've squinted a lot in my lifetime. I have crow's feet because the nerves there have pinched the skin on either side of my eyes, and that's given me little creases there that are sometimes referred to as crow's feet. Botox injections can be applied to the scalp in order to relieve tension of the scalp, and in hearing that, it should be obvious why Botox is being used to try and offset hair loss. It's decreasing the squinting, if you will, (laughs) or the tensile nature of the scalp skin, so that more blood flow can arrive at that stem cell follicle area. So Botox treatment to the scalp is actually becoming pretty common. There are a couple requirements with this Botox treatment. First of all, it has to be done by somebody who's really skilled. There are numerous images online and websites online of so-called Botox fails where people have gotten too much Botox or the injections have b- been done too deep or not at the correct locations on people's face or scalp and it can give them droopy scalp or droopy eyes, all sorts of, you know, cosmetic nightmares can occur with Botox. The second thing to understand is that Botox does eventually wear off, that botulinum neurotoxin doesn't stick around forever and provided it's done correctly at the correct dosages, it doesn't actually kill the neurons that cause that tension of the skin, so Botox injections have to be done repeatedly. The efficacy of Botox for offsetting hair loss is not clear. There aren't a lot of large-scale clinical studies on this just yet, but it does seem to be at least one reasonably safe alternative to things like minoxidil, although I think if one were to just want to increase blood flow to the scalp, things like low dose tadalafil, which doesn't seem to carry any of the side effects that minoxidil can carry, we talked about those side effects earlier, that would probably be the better alternative. Botox is a fairly invasive procedure, but some people opt for Botox treatment. In fact, there is a syndrome called cutis verticus gyrata. Some of you have probably seen this. It's more typical in men, although it does occur in women. It literally means a lumping of the skin on the scalp or gyri of the scalp. Um, gyri or gyrus pertains to the Latin word knee, so it means bump or knee, um, and so a- anytime you hear the gyri, uh, in neuroscience or in biology, you're talking about a bump. You sometimes see people who have ridges in the back where it looks as if the skin was pushed together, kind of like the, a Shar-Pei dog, but on the scalp. People with cutis verticus gyrata almost always experience pattern hair loss. Now part of the reason for that is cutis verticus gyrata is also associated with some androgen or testosterone-related hormone issues that we'll talk about in a little bit, but in addition to that, it has been shown that relieving some of those gyrata by injections of Botox to allow those folds to sit flatter, A, is effective, it can lead to less of those gyri, those bumps, and can improve hair growth in those regions even if those people don't take on any additional treatments to address the hormone issues. So that's

Andrew Huberman 1:06:27 really how people arrived at this understanding that Botox might be a good treatment in general for reducing the, um, kind of squinting of the scalp, uh, that can occur and the resulting hair loss in those regions. I'd now like to turn our attention to the chemical variables that control the duration of the growth phase of hair, the duration of that catagen phase, which is when that hair essentially recedes from the inside out, and the quiescent or semiquiescent telogen phase. There are a couple of key chemical players here that we should all be aware of. First of all, the growth factor IGF-1, insulin growth factor 1, which is produced by the liver, but that receives stimulation from the brain and pituitary to be released, is a strong regulator of hair growth, and we can think of it as the accelerator on hair growth. So it does that by extending that anagen or growth phase for longer. It doesn't necessarily speed up growth, but it extends it for a longer period of time.In addition, cyclic AMP, which is part of what's called a second messenger pathway, in fact, cyclic AMP is a second messenger, is also a key player in stimulating growth of the hair follicle. Now, cyclic AMP does many different things in many different cell types in the body. It really acts, as the name suggests, as a messenger between signals that arrive at the surface of cells and transmitting or conveying those signals to things that happen deep within the cells, such as the turning on and off of various genes. So when you hear second messenger, don't let that confuse you or overwhelm you. Just understand that the whole process of getting signals from the outside of cells into the center of cells and controlling gene expression, for instance, causing a stem cell to continue to give off daughter cells, or causing a hair cell to continue growing for longer, that whole process is a bit like a bucket brigade of handing off water or a bucket from one, uh, component to the next, or along a chain. It's like an assembly line. I think that's probably the simplest way to think about it. So for sake of this discussion, IGF-1 is known to increase the growth of hair by extending that anagen phase, as is cyclic AMP. So those are going to be considered the accelerators, at least in this conversation. The brakes on hair growth are going to be the things that either shorten the anagen phase or that extend the catagen phase or this quiescent phase, which is the telogen phase. And the two major brakes on hair growth that we want to think about are PDE, which is a phosphodiesterase, okay? Anytime you hear 'ase,' it's likely to be an enzyme. And TGF-beta2, all right? So this is a particular growth factor that somewhat counterintuitively doesn't stimulate growth, it actually stimulates lack of growth or shortens growth. So with all of that in mind, and please do also keep in mind that you don't need to remember all those specific terms. Just understand that there are some factors, like insulin growth factor one, that act as accelerators on growth, and there are factors that act as brakes on growth. We can start to think about why, for instance, half of all people by age 50 start to lose their hair. Well, they start to lose their hair because of something called androgen-related alopecia, which translated to English means testosterone and testosterone derivative induced hair loss, and this is true in men and women. So hearing that, you should probably be wondering the following thing. Young men have higher levels of testosterone than old men, right? Well, the answer is yes. Although some older men in their 40s, 50s, even 80s maintain testosterone levels similar to many men in their 20s, but most don't. It's a downward slope starting at about age 40. How steep that downward slope is depends. Women, too, have testosterone. In fact, women have higher levels of testosterone than they do estrogen. That's right. A healthy woman has higher levels of testosterone than she does estrogen. However, women on average have lower testosterone than most men. Okay? So they still have far more estrogen and far less testosterone than most men, but the level of testosterone that they have within their body is higher than the level of estrogen they have. Androgens, such as testosterone and its derivatives such as dihydrotestosterone, which will be much the topic of what we're getting into next, inhibit IGF-1 and cyclic AMP. Again, androgens such as dihydrotestosterone inhibit, prevent the action of IGF-1 and cyclic AMP, which you just learned a few moments ago act to extend the anagen or growth phase of hair, which then raises the question, well, if young people, both male and female, have higher levels of testosterone than they do when they're older, why would people lose their hair when they're older and not younger? Ah, the answer lies in the conversion of testosterone to dihydrotestosterone. Testosterone most people have heard of. Dihydrotestosterone or DHT is made from testosterone. There's an enzyme called 5-alpha-reductase that converts testosterone into dihydrotestosterone in both men and women. Dihydrotestosterone binds to the androgen receptor at five times the affinity of testosterone. So it is the most powerful androgen in humans, and it is responsible for a number of things that we all really want and like, such as mental vigor, physical vigor, strength, healing capacity, drive, libido, and on and on. So DHT itself is not bad. So if we take a step back and we acknowledge testosterone levels are higher in males and females at younger ages as opposed to older, but as they get older, there is more 5-alpha-reductase activity, which is converting more of that testosterone to dihydrotestosterone, and dihydrotestosterone inhibits hair growth by reducing IGF-1 and cyclic AMP, well, then we should all be aboard why it is that by age 50 about 50% of people experience pattern hair loss. That is androgen-dependent alopecia, okay? But translated to normal English is pattern hair loss. And in a moment you'll understand why some people lose their hair from the crown region, kind of in the back of the head or back and top of the head, whereas other people lose their hair in the front of their head, in the flanks right on either side of the midline or maybe in the midline in front all together. And that's because different people, depending on their genetic lineage, have different patterns of androgen receptors on their scalp.And the pattern of androgen receptors that you inherit indeed does come from your mother's side. And so this is what gave rise to the, the myth that if you want to know if you're going to go bald or not, just look at your mother's father. Doesn't quite work that way. In fact, if you think about the logic, you should really look at your mother's mother if you want to know your pattern of androgen receptors on your scalp. However, most women don't lose as much hair from their scalp or they have ways of covering up the hair loss in their scalp because their hair is just generally longer or they're using other approaches, so that you never really get a clear picture of what the androgen dependent hair loss was in your grandmother, okay? Now, we don't want to go too far down the genetics rabbit hole because, uh, as you know, you can't select your parents anyway, but if you want to know why, for instance, I'm losing a bit of hair on either side of the midline in the front, it almost certainly has to do with the fact that I have a higher density of androgen receptors there as opposed to, say, on the crown of my head where, for whatever reason, my hair seems to grow thickest. Other people lose hair on the crown, in the back and top, but not in the front, and some people lose it all over. Now you understand why hair loss occurs in certain regions of the body. You should also understand that the androgen receptors on the face are also what are responsible for beard growth, and this is where it can get a little bit tricky, but a lot of things will start to make sense if you can understand this and internalize this. If you have a high density of androgen receptors on your face, well then, as your DHT levels go up with age, you will be able to grow a thicker and thicker beard. In fact, it is rare to see someone who can grow a thick beard in their youth but not so much as they get older. In fact, the reverse tends to be true. So the pattern of androgen receptors differs between the scalp and the face and the back, okay? On your back you have androgen receptors and there, DHT stimulates hair growth. So if you know someone who has a very hairy back or if you have a very hairy back, that means you have a high density of androgen receptors on your back. If you have a beard and that beard is thick, well, then you have a high density of androgen receptors on your face. However, a high density of androgen receptors anywhere on your scalp is going to predispose those regions to androgen-dependent alopecia or hair loss in those particular regions, which is going to allow us to understand why all of the rest of the treatments for halting hair loss and for stimulating hair growth, almost all of those center on inhibiting either DHT directly or 5-alpha-reductase, the conversion of testosterone to DHT.

Andrew Huberman 1:15:46 So now I'd like to discuss the ways that one can chemically adjust certain things within the hair growth pathway, things like IGF-1, PDE, TGF-beta, et cetera, in order to stimulate hair growth or halt hair loss. The first thing on this list is actually going to be pretty surprising to a number of you, and that's caffeine. We all think of caffeine as a stimulant that we drink. I certainly drink coffee and yerba mate, the occasional energy drink, things of that sort. Caffeine does many things besides stimulate our central nervous system and make us feel less sleepy, however. One of the things that caffeine does is it is a fairly potent PDE inhibitor. By being a potent PDE inhibitor, it indirectly stimulates IGF-1. Why? Well, because PDE can suppress IGF-1, and by ingesting caffeine or by applying topical caffeine ointment or cream to the scalp, you can suppress PDE sufficiently enough to increase IGF-1 and increase some hair growth or at least maintain hair growth in that region. Now, this may come as a shock, it might seem a little bit esoteric or even, uh, outside the margins of typical treatments, but head-to-head, topical caffeine application can be as effective as minoxidil application without actually lowering things like blood pressure and potentially increasing prolactin and some of the other negative, let's call them negative because they are, side effects of minoxidil. So caffeine ointments and caffeine present in various hair treatments and creams, et cetera, is starting to become a more prominent theme out there. I will include a reference to caffeine and its uses for offsetting hair loss. Keep in mind that topical caffeine ointments shouldn't necessarily be applied every single day, so this is the sort of thing you might do three times a week. The concentration of caffeine in different ointments varies tremendously. Most of the studies of caffeine on the stem cell niches that control hair growth and extension of the antigen phase of hair growth have been performed in vitro in a dish. Although there are some clinical studies exploring this, they are not nearly as extensive in number or duration as the studies of minoxidil because this approach just hasn't been around quite as long. However, when comparing side effects of minoxidil, cost of minoxidil, comparing the efficacy of caffeine and minoxidil, I think caffeine as a topical treatment for offsetting hair loss stands as a pretty good choice if you're s- going to start exploring this pathway. And there's no reason to think that if you were to try the caffeine ointment and it didn't work for you or you didn't like it for some reason or you needed to stop it for some reason, that you couldn't stop it safely, because it doesn't carry all the other, kind of blood pressure related effects and prolactinemia effects that minoxidil does. So if you look out there into the hair maintenance and hair replacement literature and you look at the treatments that are being sold, don't be surprised to see caffeine there. And also, don't be surprised when I tell you what I'm about to tell you now which is, no, you can't simply just drink more caffeine in order to accomplish, uh, the goal of offsetting hair loss. It is true that when you ingest caffeine, it goes systemically. However, you have so many adenosine receptors throughout your body, those adenosine s- receptors and the parking of caffeine in those adenosine receptors is the main way in which caffeine exerts its stimulatory effects, making you feel less sleepy. So, it does that because then adenosine can't have its effects, which are to make you sleepy. Well, those adenosine receptors soak up so much of the caffeine that you would ingest orally that very, very little...... would make it to the scalp and to the hair follicles at the concentrations that you would want. So, that's why you have to rely on the application of these caffeine ointments about three times a week. Keep in mind that no one has really explored the dosages of caffeine in these ointments in a systematic way. We are still in the early stages of all this. But I do think it's important to mention caffeine because of the lower incidence of side effects, at least reported side effects, and the general safety margins, and the head-to-head, essentially comparable efficacy with minoxidil, because minoxidil has a bunch of other issues. Now, keep in mind that both minoxidil and caffeine are generally used as a preventative for reducing hair loss over time. They are not expected, and they do not, as far as we know, create new hair growth to any sufficient degree. If any of you have used caffeine ointments or minoxidil and observed new hair growth that was robust, please put that in the comment section. I'd be curious about those experiences. But as far as I know, and from the clinical literature that I read, there's no examples of that. One other point about caffeine, it does appear that caffeine can not only indirectly stimulate IGF-1 in the anagen phase of hair cell growth by way of reducing PDE and TGF-beta, but it also seems to reduce apoptosis, which is naturally occurring cell death of that stem cell niche. We've been talking a lot about the anagen, or growth, phase of hair. We also talked about the catagen, or the recession of that hair from the inside out.