How Hormones Control Hunger, Eating & Satiety

**Andrew D. Huberman** (0:00)
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. 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 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've long been a fan of getting blood work done, and the simple reason for that is that most of the things that you want to know about your health, such as hormones, metabolic factors, blood sugar levels, et cetera, can only be analyzed from blood. And nowadays there are also excellent DNA tests that can also give you valuable information about what's going on at the cellar, molecular, even the neural circuit level within your brain and body. InsideTracker makes getting blood and DNA tests easy. You can go to a testing site where they draw your blood, they take your DNA sample, or they can come to your home if you prefer that. As well, they have a really amazing dashboard. The dashboard lets you understand what your levels of various hormones and metabolic factors, et cetera, mean and what you should do about them. I think that's one of the main things that really separates InsideTracker apart from other blood and DNA tests. Most tests, you get the results back, but there are no directives about what to do specifically in order to bring the numbers into the ranges that you would like for your goals. InsideTracker makes all of that extremely simple and extremely clear. If you'd like to try InsideTracker, you can go to insidetracker.com/huberman.
And if you do that, you'll get 25% off any of InsideTracker's plans. Use the code Huberman at checkout. That's insidetracker.com/huberman to get 25% off any of InsideTracker's plans. Today's episode is also brought to us by Athletic Greens. Athletic Greens is an all-in-one vitamin, mineral, probiotic drink. I started taking Athletic Greens back in 2012, and I've taken it ever since. So I'm delighted that they're sponsoring the podcast. The reason I started taking Athletic Greens, and the reason I still take it now, is that Athletic Greens really lets me cover all my nutritional bases in terms of vitamins, minerals and probiotics. There's so much data now pointing to the fact that the gut microbiome and the gut brain axis is important for metabolism and for endocrine health. The vitamins, minerals and probiotics in Athletic Greens make me feel confident that I'm covering all my bases. I do take other supplements, but with Athletic Greens, I know that I've got all the foundational stuff handled. It also tastes really good. Tastes fine on its own. You can mix it with water, which is what I do. I add a little bit of lemon juice or lime juice because I like a little tartness flavor in there as well. But most people just mix it with water. It mixes up super easily. I drink it once or twice a day, usually once mid morning and once again in the afternoon. If you'd like to try Athletic Greens, you can go to athleticgreens.com/huberman.
And if you do that, you can claim their special offer, which is a year supply of vitamin D3K2. There is now a ton of evidence that vitamin D3 is involved in countless metabolic processes, hormonal processes that are important for overall health and well-being. Vitamin D3, you can get from the sun, of course, but most people are deficient in vitamin D3. So if you go to athleticgreens.com/huberman, you'll get the athletic greens, you'll get the year supply of vitamin D3 and K2, and you'll get five free travel packs. So once again, it's athleticgreens.com/huberman to get athletic greens, the vitamin D3 K2, that's a year supply plus the five free travel packs. Today's episode is also brought to us by Monk Pack. Monk Pack is a company that makes keto-friendly snacks that taste incredible, but have just one gram of sugar or less. And indeed they taste incredible. In fact, my production team here at the Huberman Lab podcast teases me because I actually have to keep the boxes of Monk Pack bars in my basement because otherwise I'll tear through all of them. I remember the first time I tasted it I was like, all right, here we go, a keto bar. I'm not a big fan of bars in general. Most of them don't taste good to me. And I tasted the Monk Pack bars and they are absolutely awesome. They come in a lot of different flavors. I'm partial to the Carmel sea salt one, but they also have a sea salt dark chocolate, peanut butter, dark chocolate. They have a bunch of flavors. They're all incredible. I've tried them all, which is why I keep them in my basement. As I've mentioned previously on this podcast, I'm neither keto nor carbo. I don't really follow a particular diet in that sense. I eat in a way that maximizes my alertness and my levels of focus during the day when I want to work and that maximize my transition to sleep at night. So I basically eat low carb keto-ish during the day. And I know the ketonistas will say that I'm not in ketosis and I can manage to get into ketosis. But the main idea is I keep my carbohydrates low during the day. And then at night, I do eat carbohydrates. So for me, the Monk Pack bars are a really good snack, usually in the afternoon, maybe with a cup of coffee, especially if I'm going to train soon after that, or if I just want to snack and I'm going to continue working. As I mentioned before, they are absolutely delicious. They also don't have any of the stuff that's bad for you. No soy, trans fat, sugar, alcohol, artificial colors, all that stuff that we know we should avoid. If you want to try Monk Pack bars, you can go to Monk Pack. That's M-U-N-K, monkpack.com and enter the code Huberminute checkout and you'll get 20% off your first purchase of any Monk Pack product. That's Monk Pack, munkpack.com and enter the code Huberminute checkout to get 20% off your purchase. This month, we're talking all about hormones. Hormones are incredible and they control so many processes in the brain and body. Last episode, we talked about the role of estrogen and testosterone. Today we're going to talk about how hormones impact feeding and hunger as well as satiety, the feeling that you don't want to eat or that you've eaten enough. Now it's important to understand that hormones don't work alone in this context. Today I'm going to describe some hormones that have powerful effects on whether or not you want to eat more or less or stop eating altogether. But they don't do that on their own. They do that in cooperation with the nervous system. So today I would say as much or perhaps even more than any other episodes, we're going to hear a lot of biology, but there are multiple what I'm going to call entry points for tools that you can apply in order to regulate your levels of hunger, your meal timing, your levels of satiety, of not wanting to eat more. And many of this is actionable with behaviors. But of course, we're also going to talk about supplements. And we're actually going to talk about a little bit of brain machine interface devices that can actually be involved in manipulating these incredible things that we think of as hunger and appetite and satiety. So the first thing that you need to know about the nervous system side, the neural control over feeding and hunger is that there's an area of your brain called the hypothalamus. It's in the forebrain, which tells you it's in the front of your brain, and it's at the base of the forebrain. Now, the hypothalamus contains lots of different kinds of neurons doing lots of different kinds of things. There are neurons in your hypothalamus controlling sexual behavior, controlling body temperature, controlling circadian rhythms, the desire to sleep or be awake, even neurons controlling rage. They're actually neurons that if we were to stimulate them would send you or anyone into a rage. They're just powerful control centers for the brain and body. There's a particular area of the hypothalamus called the ventromedial hypothalamus. And it's one that researchers have been interested for a long time now in terms of its relationship to hunger and feeding. And the reason is it creates these paradoxical effects. What do I mean by that? What they found was that sometimes lesioning or disrupting the neurons in the ventromedial hypothalamus would make animals or people hyperphagic. They would want to eat like crazy. And other lesions in other individuals or animals would make them anorexic. It would make them not want to eat at all. It would make food aversive. So that means that the ventromedial hypothalamus is definitely an interesting control station for hunger and feeding and satiety. But it doesn't really tell you what's going on at a deeper level. In fact, it's a little bit confusing or paradoxical. Turns out that there are multiple populations of neurons in there. We're going to talk about those. Some are promoting feeding and some are promoting not feeding or not eating. Now the other neural component of all this that you need to know about actually has to do with your mouth. So there's an area of your cortex, so that's a little bit further up in your brain, called the insular cortex, and it processes a lot of different kinds of information, mostly information about what's going on inside you, so-called interoception. The insular cortex has neurons that get input from your mouth, from the touch receptors in your mouth. An insular cortex has powerful control over whether or not you're enjoying what you're eating, whether or not you want to avoid what you're eating, whether or not you've had enough, or whether or not you want to continue eating more. And that has to do, believe it or not, with the touch or sensation of eating. I'm very familiar with this. I'm one of these people, I love eating so much, that I just like the mere act of chewing. I like celery sticks enough, I'm not crazy about them, but they taste fine to me, and I like chewing on celery sticks, but I actually just like chewing on them. I could eat all day long, except that it's not healthy to do that. But the mere act of chewing for me is very pleasurable. People who chew gum feel this way as well. And just as a point about gum or chewing, if you chew something like celery or cucumber slices or chew gum, provided it doesn't have any sugar or caloric content, it's not going to drive increased hunger. That generally isn't the case. But if you eat something with sugar, as we'll find out, it has a very specific action in the insular cortex and in other areas of your nervous system that promotes the desire to eat more. But the key point right now is to know that you got these two brain areas, the ventromedial hypothalamus, that's involved in hunger and lack of hunger, sort of an accelerator and a break on feeding. And you have this insular cortex that gets input from your mouth and cares about chewing and the consistency of foods and all sorts of interesting things that are just very tactile. And I think most people think about the touch receptors on, excuse me, the taste receptors on the tongue, but we often don't think about the touch or tactile essence of food. And the thing that comes to mind just now is I've gone to sushi several times and some people really like the urchin. I don't like the urchin. There's something about it that kind of creeps me out about the consistency. Other people love it. So it's highly individual and it's probably learned and there's some probably cultural background to this. If you were raised eating urchin, some people love that consistency or that touch. So touch has a lot to do with whether or not you want to eat or not. Now, let's get back to the ventromedial hypothalamus. Sometimes it makes animals or people want to eat more, sometimes less. So what's going on there? There's a classic experiment that was done in which researchers took two rats and so-called parabiased them to each other. What that meant is that they did a little surgery and they linked their blood supply so that they were forever physically linked to one another and could exchange factors in the blood, but their brains were separate, their mouths were separate, and they essentially did everything separately except that they were linked to one another. So they had to walk together and go to the same places in order to do it. This parabiases experiment revealed something really important. When they lesioned the ventromedial hypothalamus in one of the rats that was connected to the other rat, that rat got very, very fat. It's just really obese, huge rat, super rat, jumbo rat. The other one, however, got very thin. It actually lost weight, despite consuming the same amount of food that it had prior to the other one getting the lesion. So what does this tell us? This tells us that there's something in the blood that's being exchanged between the two animals because it was their blood supply that was linked. And that tells us that there's hormone or endocrine signals that are involved in the desire to eat and hunger and appetite. And so next we're going to talk about what those endocrine signals are. And then I'm going to immediately point to some entry points that you can use. And you can use these even if you're not parabiased to anything. And that can allow you to time your meal frequency and predict when you're going to be hungry or not, as well as drive up appetite, believe it or not, there are people out there who are trying to eat more. Although I think far many more people are trying to eat less because nowadays, the data just point to the fact that there is essentially an epidemic of diabetes, type two diabetes and obesity. And most everyone agrees now that maintaining a healthy body weight and body weight composition is one of the best paths to longevity and to just feeling very good and actually being able to think cognitive functioning is actually linked to levels of adipose tissue and so forth. So let's talk about the endocrine factors that regulate feeding hunger and satiety. One of the really exciting things to emerge in this science of feeding and appetite in the last 20 years is the discovery of another brain area, not just the ventromedial hypothalamus, but it's an area of the brain called the arcuate nucleus. And the arcuate nucleus has some really fascinating sets of neurons that release even more incredible molecules and chemicals into the blood. And these chemicals act as accelerators on feeding and appetite or breaks. And the really cool thing is that you can actually control these molecules through simple behaviors. And once you understand what these molecules are, you'll start to understand why that's the case and the control points that you have right now in order to control your appetite in either direction, increase or decrease. So first of all, there are a set of neurons in this arcuate nucleus called the PMOC neurons. I don't want to get into what the acronym stands for, but I'll do it anyway. It's the pro-opio melanocortin system. So these are PMOC neurons, pro-opio melanocortin. And if you heard milano, that should tell you it has something to do with pigmentation in skin cells or in hair cells, pigmentation of some sort because of melanin. Last episode, I talked a little bit about the relationship between light, dopamine and melanin. So you should already be thinking, wait, milano means it probably has something to do with that system. And indeed it does. Now the PMOC neurons make something called alpha MSH, melanocytes stimulating hormone, alpha melanocytes stimulating hormone. If you don't want to remember any of the other acronyms and terms I've talked about this episode so far, do try and remember MSH, okay? Mouse, Sam, Hamster, MSH, okay? MSH reduces appetite and it's a powerful molecule, all right? So just put that on the shelf, MSH reduces appetite. Now there's another population of neurons in the arcuate nucleus called the AGRP neurons. And there I'm truly not going to read you what that stands for because it's related to the mouse strain it was first identified in, but humans make these have these cells as well. But AGRP neurons, the AGRP neurons stimulate eating. And anytime you are approaching food or you feel some excitement about food or anxiety, because some people actually experience a kind of heightened anxiety, some people actually get a little bit of a resting tremor before they eat, even if they don't have any sort of eating disorder, there's kind of a ramping up of autonomic activity. That's largely due to the activity of these AGRP neurons. So the activity in these AGRP neurons goes way up when animals or people are starved. And I don't mean starved for long periods of time, but I mean when they haven't eaten for a while. And the activity of MSH, the release of MSH goes up when we've eaten. However, there are other things that will stimulate the release of things like MSH. So just briefly, the experimental evidence. If you kill AGRP neurons, animals and people stop eating. There are people who have lesions, they just stop eating. They become anorexic. That's actually, I know you're familiar with anorexia as a clinical term, but that's actually a term that's used in the scientific literature about a pattern of behavior, okay? As well as a clinical term, of course. If you were to stimulate the AGRP neurons, animals or people eat like crazy. They will eat to the point where they burst, which just sounds horrible, but it just tells you this is the accelerator on eating. And yes, as relationship to the ventromedial hypothalamus I talked about earlier, but I don't want to go back there just yet. We will circle back. So melanocyte stimulating hormone, such an interesting hormone. This thing can shut down the desire to eat. The melanocyte stimulating hormone is released from the medial pituitary. We talked about the pituitary last time. This is a gland that is very closely positioned to the hypothalamus. Actually some of the hypothalamus neurons actually project their neural connections directly into the pituitary to release things like gonadotropins and luteinizing hormone, stuff we talked about last time in reference to testosterone and estrogen. But MSH is released from the medial portion of the pituitary and it stimulates the desire to not eat, to cease eating. What's really interesting is that melanocyte stimulating hormone is activated by ultraviolet light. And it's not activated by ultraviolet light to the skin or directly to the pituitary. It's activated by ultraviolet light to the eyes. Now, if you've been watching this podcast or listening to this podcast for any period of time, or you've heard me on other podcasts, or you follow my Instagram, I am a big fan of this whole thing of getting morning light in order to synchronize circadian rhythms, et cetera, avoiding light in the middle of the night. This is yet another reason why getting ample light, ideally sunlight, but it could be other sources of UV light to the eyes, stimulates MSH, this has been shown over and over again, and keeps the desire to eat or appetite in check in healthy ranges. This is also why in the spring and summer months, animals and people eat less. Now for hibernating animals, it's different because the bear hibernate, and actually bears don't truly hibernate, technically by scientific criteria, they don't hibernate, but they go into a kind of torpor. The hibernating animals, they don't eat much because they're in burrows or dens, or they're just wrapped up in a little ball or whatever it is that hibernating animals do. So they're of course going to eat far less in the winter, but that's a unique scenario. We are not hibernating animals, but humans generally have greater appetite in the cold winter months. And it's not just because of the holidays and the abundance of food that we're presenting ourselves with. But when we get a lot of sun, our appetite is reduced, or at least it's easier to control. And that is due in part because if you're getting ample sunlight to the eyes, it's converted into a signal for the MSH neurons, the neurons that release MSH, excuse me, these palm seed neurons release MSH. And then MSH can bind its receptors and can keep the break on appetite in check. So the takeaway tool from this is make sure you're getting enough light, not just in the morning, but throughout the day. And yes, it has to be light to your eyes. And blasting your eyes with sunlight or artificial light to the point where it's damaging or painful won't accelerate or improve this process. It's about getting photons, ultraviolet light to the eyes consistently throughout the day. That's best accomplished by not wearing sunglasses, provided you can do that safely. And if you don't have access to enough sunlight, then you can do this with artificial light. This also points again to our old friends, the blue blockers. Many people know I'm not a huge fan of blue blockers, especially not during the daytime because they block a lot of the UV and shorter wavelength light that you want and need to create alertness, but also to create release of MSH from the medial pituitary. Now, there are people out there, subcultures, that actually inject MSH, that are taking MSH or things similar to it. I am not suggesting people do that, but there are three main consequences of doing that. First of all, it reduces appetite, no surprise there. They're actually using it as a dieting drug. This is kind of in the underground. I don't know what the legal status is. And again, I'm not promoting that people do it. Two, it makes them very, very tan, which makes sense, right? Melanocyte stimulating hormone. And the third is it purportedly, never tried it, purportedly sends libido through the roof, to the point where it's actually distracting for other activities. It actually can create pre-epism, which is a kind of chronic erection in males, to the point where it actually can be physically damaging to the genitalia. So this is a drug of, or I don't know whether or not to call it a drug. It's a substance that one can regulate with healthy levels, with sunlight and perhaps artificial UV light. I have not heard much about treatments for obesity involving getting ample sunlight or getting ample UV light. But to me, the logic is just very clear. And so if you're pursuing those avenues, you might want to, you certainly should talk to your physician, but you might want to think about how some of those logic hangs together. Absolutely fascinating hormone. I think most people aren't aware of it. And the subcultures that are aware of it are using it to very particular endpoints and they're using it at supraphysiological levels. That's enough about that, because I really don't know. I've talked to a few people in research, believe it or not, for this podcast. I reached out to a few people and asked whether or not these side effects, in air quotes, I've heard about are true and indeed they're true. But again, that's supraphysiological. Controlling MSH, it's actually alpha MSH levels through viewing ultraviolet light seems like an interesting and mechanistically logical thing to do. If your goal is to keep appetite in check. So MSH inhibits hunger. Next, let's talk about a hormone peptide that activates hunger. And this is a really interesting one because it relates to when you get hungry in addition to the fact that you get hungry at all. And it's called ghrelin. It's spelled G-H-R-E-L-I-N.