# Using Caffeine to Optimize Mental & Physical Performance - **Show:** Huberman Lab - **Published:** 5 Dec 2022 - **Source:** https://hubermanlab.com/using-caffeine-to-optimize-mental-and-physical-performance - **Transcript:** https://podcasts.opennash.com/shows/huberman-lab/using-caffeine-to-optimize-mental-physical-performance-1fb12b/ - **Provider:** OpenNash Podcasts (machine-generated) ## In brief Andrew Huberman argues that caffeine is more than a stimulant. It blocks adenosine, the chemical that makes us sleepy. It also raises dopamine and acetylcholine, and it acts as a subconscious "reinforcer" that makes us like whatever we consume it with. Used at about 1-3 mg per kilogram of body weight, early in the day, he says it can improve mood, memory and exercise performance. The tension is that caffeine does not create energy. It only shifts when sleepiness arrives. The episode moves from mechanism to practical rules: delay caffeine after waking, stop it 8-12 hours before bed, and cycle or pause use to keep its effects strong. It ends with the trade-offs, including sleep loss, anxiety and dopamine "stacking". ## Key insights 1. **Caffeine borrows energy; it doesn't create it** Caffeine blocks adenosine receptors, so the sleepy signal builds up behind them. When the caffeine wears off, Huberman says, you face a backlog of adenosine and feel extra sleepy. 2. **Delay caffeine 90-120 minutes after waking** Huberman says morning light and movement spike cortisol, which helps clear leftover adenosine. Waiting then lets caffeine work on a cleaner slate and, he says, can prevent the afternoon crash. 3. **Dose by body weight: 1-3 mg per kilogram** For a 100 kg person that is 100-300 mg in one sitting. Huberman warns that popular vendors' coffees can hold 400-1,000 mg, which may cause anxiety, headaches and dependence. 4. **Caffeine trains you to like what it accompanies** Bees preferred nectar flavors paired with caffeine even after it was removed, and Huberman says children did the same with yogurt. The reward is subconscious, so caffeine can lock in tastes, mugs, company and even exercise. 5. **Pausing caffeine boosts its performance effect** A study of 20 days of caffeine versus placebo found a bigger aerobic boost after abstinence. Huberman cites shorter breaks of 2-5 days and every-other-day use as gentler options. ## Questions this episode answers ### How much caffeine is a sensible dose? Huberman suggests 1-3 milligrams per kilogram of body weight in a single sitting, so about 100-300 mg for someone who weighs 100 kg. He advises people who aren't used to caffeine to start at the low end. ### When should I stop drinking caffeine so it doesn't wreck my sleep? Huberman says caffeine has a "quarter life" of about twelve hours, meaning roughly 25% is still active twelve hours later. He recommends avoiding it in the 8-12 hours before bed, and he mostly stops by noon. ### Why does Huberman say to wait before my first coffee? He says morning light and activity trigger a cortisol rise that helps clear adenosine, the chemical that builds sleepiness. Drinking caffeine at once blocks adenosine without clearing it, which he links to an afternoon crash. ### What does it mean that caffeine is a "reinforcer"? It means caffeine makes you like and seek out whatever you consumed it with, without you noticing. Huberman cites a bee study and yogurt tests where flavors paired with caffeine were preferred even after the caffeine was removed. ### Does caffeine help or hurt mood and health? Huberman says studies link regular intake at sensible doses to fewer depressive symptoms, and possibly to lower Parkinson's and Alzheimer's risk. He cautions that these are associations, caffeine is not a treatment for severe depression, and too much can raise anxiety. ## Facts - **Andrew Huberman** [0:00:00]: "Estimates are that more than 90% of adults and as many as 50% of kids, that is adolescents and teenagers, use caffeine on a daily basis." - **Andrew Huberman** [0:04:22]: "it was actually discovered in Gila monsters. These are these um reptiles that can go long periods of time without eating" - **Andrew Huberman** [0:05:50]: "and the smoked varieties are thought to perhaps be carcinogenic, that is, pro-cancer causing" - **Andrew Huberman** [0:06:49]: "it turns out it also stimulates thermogenesis. Now, thermogenesis is the active utilization of more metabolic energy" - **Andrew Huberman** [0:07:49]: "it communicates to those white fat cells and helps convert them into beige and brown fat cells." - **Andrew Huberman** [0:13:37]: "we experience an increase in alertness within about five minutes, and that increase in focus and alertness peaks around thirty minutes after ingestion of caffeine and persists for as long as sixty minutes." - **Andrew Huberman** [0:18:28]: "And the title of the paper is caffeine in floral nectar enhances a pollinator's memory of reward." - **Andrew Huberman** [0:23:14]: "but rather caffeine seems to stimulate the release of dopamine in the parts of the brain that are associated with alertness and cognition, meaning the forebrain." - **Andrew Huberman** [0:32:46]: "caffeine is what's called a methylxanthine. It's a plant alkaloid." - **Andrew Huberman** [0:41:17]: "one to three milligrams of caffeine per kilogram of body weight would mean for me, I could safely ingest one hundred to 300 milligrams of caffeine in a single dose" - **Andrew Huberman** [0:46:02]: "the small coffee or the medium coffee, for instance, can contain as much as 400 to 600 milligrams of caffeine, and that the large coffee that is often sold at those commercial vendors can contain" - **Andrew Huberman** [0:55:55]: "it's been shown in studies on humans that getting bright light in your eyes in the first hour after waking, or as soon as possible after waking, increases the peak of that cortisol pulse by 50%" - **Andrew Huberman** [1:01:25]: "Caffeine has a quarter life of about twelve hours. That means that if you were to ingest a cup of coffee at" - **Andrew Huberman** [1:10:01]: "the dosages of theanine that are effective for offsetting the jitteriness of caffeine is 200 to 400 milligrams" - **Andrew Huberman** [1:13:53]: "But assuming that you are getting adequate levels of calcium, there is no direct relationship between caffeine intake and osteoporosis, at least not that I'm aware of." - **Andrew Huberman** [1:17:37]: "By examining more than a thousand, so in this case, 1,410 men or more than a thousand women, that there are increases in sex hormone binding globulin associated with increased intake of coffee in particular." - **Andrew Huberman** [1:20:02]: "the one that I'm particularly fond of was published in 2019 in psychiatry research. And the title of the paper is Inverse Association Between Caffeine Intake and Depressive Symptoms in US Adults." - **Andrew Huberman** [1:34:15]: "They had people either ingest three milligrams per kilogram of caffeine for twenty consecutive days" - **Andrew Huberman** [1:40:02]: "caffeine increased peak aerobic cycling power in the early follicular, preovulatory, and mid-luteal phases of the menstrual cycle." - **Andrew Huberman** [1:41:56]: "medieval practices of children being taught information and then being thrown literally into cold water to stimulate the release of adrenaline" - **Andrew Huberman** [1:50:25]: "and the title of the study is Blood Dopamine Level Enhanced by Caffeine in Men After Treadmill Running." - **Andrew Huberman** [1:32:25]: "This was something that was actually covered in beautiful detail in a book by Michael Pollan, all about caffeine." - **Andrew Huberman** [2:07:37]: "If you put caffeine into yogurt of different flavors, even plain yogurt, which most kids don't like, they will come to prefer whatever flavor contain the caffeine" ## Transcript **[0:00:00] Andrew Huberman:** 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 caffeine. Caffeine is one of the most widely used substances on the planet. Estimates are that more than 90% of adults and as many as 50% of kids, that is adolescents and teenagers, use caffeine on a daily basis. Now, caffeine is an amazing molecule. **[0:00:33] Andrew Huberman:** Most people are familiar with caffeine's ability to increase alertness and to reduce our feelings of sleepiness and fatigue, and indeed it does that. But what most people are not aware of is that caffeine acts as a strong reinforcer. What I mean by reinforcer is that when caffeine is present in a drink or food, and yes, indeed, caffeine is present in many foods, even unbeknownst to us, when it's present in drinks and foods, we actively come to like those foods and drinks more than if caffeine were not contained in those foods and drinks. **[0:01:07] Andrew Huberman:** So it reinforces our liking of particular foods and drinks, and indeed, it even reinforces our liking of the containers they are consumed from and the company we keep when we consume foods and drinks that contain caffeine. That is, caffeine is not just a stimulant, caffeine is a reinforcer, and it's a reinforcer that plays an active role in almost everybody's daily life. We can say that with confidence because, as I mentioned a moment ago, more than 90% of people are consuming caffeine, and most people think that they consume caffeine because it makes them feel more alert. **[0:01:41] Andrew Huberman:** But there are many reasons why you're consuming caffeine, and I'm not going to tell you that consuming caffeine is necessarily bad. In fact, today I'm going to tell you about many of the positive health benefits of caffeine, including neuroprotective effects, antidepressant effects, and certainly performance-enhancing effects, both for mental performance and for physical performance. Now, that said, there are certain situations in which you want to avoid caffeine, and there are certain people who might opt to avoid caffeine. **[0:02:08] Andrew Huberman:** That's especially the case when one thinks about caffeine, not just as a stimulant, but as a reinforcer. In fact, caffeine is such a strong reinforcer that if even tiny amounts of caffeine are present in certain foods and drinks, you will very quickly come to prefer those foods and drinks over other choices, which can be a good thing or a bad thing, depending on what sorts of food and drink choices you're trying to make. So today, I'm going to inform you about how caffeine works at a mechanistic level. **[0:02:33] Andrew Huberman:** I promise to do that with a minimum of nomenclature and such that, even if you don't have a background in biology, you will be able to digest that information easily. And then I'll tell you how to use caffeine to your advantage, or, conversely, how to avoid caffeine at certain times to your advantage. So today's episode will focus both on mechanisms and tools, that is the use and leverage of caffeine to improve mental health, physical health, and performance. **[0:02:58] Andrew Huberman:** Before we go any further into today's discussion, I want to tell you about some recent results about a molecule that's found in certain caffeinated beverages and that has been proven to be very useful for both weight loss, mental performance, and controlling blood sugar levels. And that's GLP-1 or glucagon-like peptide-1. Glucagon-like peptide-1 is found in the brain and body. It acts both on the brain and body. It does many different things, but one of its primary effects that's been discovered is to reduce hunger, and it does that two ways. **[0:03:30] Andrew Huberman:** It does that by activating certain neurons in your hypothalamus, so that's a brain region that controls hunger and satiety. It makes us feel full at the level of the brain, so it makes us feel sated, that is, and it actually makes us feel full. Turns out that GLP-1 acts on certain receptors in the gut to make us feel as if we've ingested enough food. It doesn't necessarily make us feel as if our gut is distended, but it makes us feel full. **[0:03:54] Andrew Huberman:** That's really interesting because if you think about it, when we eat, our stomach fills up, obviously, and that information has to be communicated to the brain such that the brain can then send satiety signals that actually shut off our hunger. And believe it or not, the brain actually activates signals to reduce the desire to chew when our stomach is full. And GLP-1, as I mentioned, works on the brain to create these feelings of satiety, as if we've had enough and to reduce our desire to eat more. **[0:04:22] Andrew Huberman:** And GLP-1 acts directly on the gut to give us a slight sense of fullness in the gut, which then is communicated to the brain. So really, there are two parallel signals being sent when we have GLP-1 present in our system. A little bit of relevant history on GLP-1, it was actually discovered in Gila monsters. These are these um reptiles that can go long periods of time without eating, and a very clever scientist decided to study why it is that certain animals, like Gila monsters, can go a long period of time without ingesting anything. **[0:04:50] Andrew Huberman:** And it's because they produce very large amounts of GLP-1. They isolate the peptide from GLP-1, then they looked for the analogous peptide in humans, and it turns out that does exist, and as I mentioned, it's released in both brain and body to make you feel full and sated. Now, why am I telling you all this? Well, today we're going to talk about caffeine, and there's one particular caffeine source, which is yerba mate, and there's some other forms of teas similar to yerba mate that stimulate the release of GLP-1 significantly. **[0:05:19] Andrew Huberman:** There are also nowadays drugs which are called analogs of GLP-1, so these are drugs that mimic or are identical to the kind of GLP-1 that you would make. And those drugs are proving to be very effective for the treatment of certain forms of diabetes and for the treatment of obesity, but they trigger enormous amounts of GLP-1 pathway activation. So those are extreme cases for people that are really struggling for weight loss, but the clinical trials and the data that are out there in the general population now are very, very promising for GLP-1 analogs. **[0:05:50] Andrew Huberman:** Yerba mate tea, provided it's not the smoked variety, and I mention that because a number of people have cued me to the fact that yerba mate teas come in smoked varieties and non-smoked varieties, and the smoked varieties are thought to perhaps be carcinogenic, that is, pro-cancer causing. So I advise people to avoid smoked varieties of yerba mate tea. But yerba mate teas are known to stimulate significant amounts of GLP-1 release, and so they can be effective as a weight loss tool, mainly by blunting appetite, and again, they do that both at the level of the brain and at the level of the gut. **[0:06:25] Andrew Huberman:** Now, all of what I just told you has been known for some period of time, but there are a new set of findings that were just published in Cell Reports Medicine, Cell Press journal, excellent journal, which indicate exactly how it is that GLP-1 stimulates both satiety and can trigger additional weight loss through other mechanisms. And I find the mechanism to be really interesting and actually really important given some other topics we've covered on this podcast before. **[0:06:49] Andrew Huberman:** So the basic finding is that GLP-1, whether or not it's stimulated through the release of a analog drug that one is prescribed, or by drinking yerba mate tea, for instance, and stimulate release of your own so-called endogenous GLP-1. Yes, it makes you feel more full at the level of brain and body, but it turns out it also stimulates thermogenesis. Now, thermogenesis is the active utilization of more metabolic energy, and fat cells, in particular, so-called beige and brown fat cells, are a potent source of thermogenic activity in your body. **[0:07:25] Andrew Huberman:** The basic background is that you have white adipose cells, so white fat cells, you have beige fat cells, and you have brown fat cells. And the beige and brown ones are fat cells that you actually want more of. They are not abundant under your skin, they're abundant really around your clavicles and your upper neck. They are the ones that generate heat, and the beige and brownness of them is actually the consequence of having a lot of mitochondria in those cells. **[0:07:49] Andrew Huberman:** When GLP1 is elevated in your system, it turns out that it communicates to those white fat cells and helps convert them into beige and brown fat cells. That is, it takes fat cells that are not doing anything useful for you except being stored energy, and I think most people out there would like to have fewer of those white adipose cells. There are few of you out there that actually need more of them that are too thin, too lean, but most people are suffering from having too many of these white adipose cells. **[0:08:17] Andrew Huberman:** Well, when you ingest yerba mate tea, or you were to take a GLP-1 analog, or stimulate GLP-1 in any number of different ways, yes, you stimulate increased satiety, but you're also stimulating the conversion of these white fat cells into beige and brown fat cells, which makes you more thermogenic and over time raises your basal metabolic rate, so you're burning more calories even at rest. It also makes you feel as if you're more comfortable in colder environments at rest. **[0:08:46] Andrew Huberman:** This is very much the same as the mechanism that's induced when you were to say take a cold shower or do regular ice baths or get into cold water regularly. That, too, stimulates the conversion of white fat cells to beige and brown fat cells. So I like these findings very much because they provide a mechanistic coherence. They provide that is a really nice story as to how something like GLP-1 could be so effective for weight loss. **[0:09:11] Andrew Huberman:** Yes, on the one hand, GLP-1 is reducing appetite, and that, of course, will help people maintain or lose weight, but it's also increasing basal metabolic rate, and we now know how that's accomplished. It's likely accomplished at least through this one mechanism by the stimulation of conversion of these white fat cells which don't do much for us except at as energy storage units to these metabolically mitochondrial rich beige and brown fat cells which you can think of as sort of the oil in the candle that allows your furnace your metabolism to burn at a higher temperature and a higher rate So that's the mechanism and the basic tool takeaway is that if you are somebody who's interested in losing weight and **[0:09:50] Andrew Huberman:** you want to leverage the GLP-1 pathway drinking a cup or two of yerba mate tea early in the day would be a great way to stimulate GLP-1 release There are other ways to stimulate GLP-1 release You can get it through certain forms of exercise in particular fasted exercise This is actually a vote in favor of fasted exercise There's a debate as to whether or not fasted cardio burns more fat than non-fasted cardio and the data basically say no it doesn't really matter but that doesn't really take into account the longer arc of things like GLP-1 release so that needs to be taken into consideration So you could do fasted cardio, you could drink yerba mate tea, keeping in mind that **[0:10:25] Andrew Huberman:** yerba mate tea does contain caffeine. We'll talk more about the specific forms of stimulants, including caffeine that mate has, but mate would be a great way to stimulate GLP-1 release. And then, of course, for those of you that are interested in more robust activation of GLP-1, then perhaps you might want to consider some of the new prescription GLP-1 analogs that are out there, but that's a more severe uh stimulus for GLP-1, of course. And for everybody, regardless of whether or not you're trying to lose weight, gain weight, or maintain weight, I think we're going to be hearing a lot more about GLP-1 analogs and drinks and supplements and things of that sort that stimulate GLP-1 in the very near future **[0:11:02] Andrew Huberman:** because it does appear to be a very important biological mechanism. 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. Let's talk about caffeine. So, as I mentioned earlier, caffeine is consumed by basically most all adults every single day and consumed at very regular times each day. **[0:11:34] Andrew Huberman:** In fact, if you were to take a look at your caffeine intake or the caffeine intake of somebody close to you, what you would realize is that they don't do so well if their caffeine intake arrives even ten, twenty, or thirty minutes past their expected or usual intake of caffeine. That's pretty remarkable. And it brings to mind ideas that we are all quote unquote addicted to caffeine or that caffeine is somehow bad. I'm certainly not going to make the argument that caffeine is bad. **[0:12:03] Andrew Huberman:** First of all, I'm a regular caffeine user. I wouldn't call myself a caffeine abuser, but I am a regular caffeine user, and caffeine is known to have certain health benefits. I listed off a few of them earlier, but I'll mention those again now before going forward. Caffeine is known to have certain neuroprotective effects, and that is because of its ability to increase neuromodulators such as dopamine, but also other so-called catecholamines like norepinephrine. If you don't know what those names mean, these are molecules that increase levels of alertness, motivation, and drive. **[0:12:34] Andrew Huberman:** And so then, therefore, not surprisingly, the large scale analyses of the relationship between depression and caffeine shows that provided people are not drinking so much caffeine that it makes them overly anxious, that regular intake of caffeine is inversely related to levels of depression. So it may have some antidepressant effects, and those could be direct or indirect. What do I mean by that? Well, you could imagine that if people are ingesting caffeine and they are more motivated to do work and pursue quality social interactions, then the probability that they will have depression could be lower. **[0:13:07] Andrew Huberman:** It could also be that there are direct effects on the chemical systems of the brain that relate to mood and well-being that could offset depression. It is not clear whether or not the effects of caffeine in countering depression are direct or indirect. Nonetheless, there's a relationship there, and it's an interesting and positive one, or I should say negative correlation, positive uh effect overall on mood and well-being, to be exact. Now, it's also the case that caffeine can improve mental performance and physical performance. **[0:13:37] Andrew Huberman:** This has been demonstrated in tens of thousands of studies. I will review a few studies on this in particular today, but to just give you a sense of how caffeine works at the level of its timing and impact on mental performance and physical performance. When we ingest caffeine, provided that we don't have a lot of food in our stomach and that our blood sugar isn't particularly high, generally, we experience an increase in alertness within about five minutes, and that increase in focus and alertness peaks around thirty minutes after ingestion of caffeine and persists for as long as sixty minutes. **[0:14:10] Andrew Huberman:** Now, this is assuming that one takes caffeine in pill form or drinks the entire caffeine drink within a short period of time. But a little bit later I'll talk about how you can consume caffeine at regular intervals while doing mental work or physical work in a way that can further increase mental performance and physical performance. But let's just touch on what caffeine intake really does for mental performance and physical performance. Perhaps the most robust finding across all of the studies that I have examined is that caffeine reduces our reaction time. **[0:14:41] Andrew Huberman:** That is, it improves our reaction time. It doesn't make it longer, it makes it shorter. So, for instance, in a laboratory study where people were asked to uh hit a lever every time they hear a tone, you can greatly reduce the time between the tone and the pressing of the lever if people ingest caffeine about thirty minutes before they do that task. Now that seems like a trivial task but this is also seen in the domain of sports performance and even in cognitive performance where people have to arrive at a particular answer to a question and the answer to that question has to be pulled from their memory banks within their brain their hippocampus for instance a brain structure involved **[0:15:17] Andrew Huberman:** in memory And if you are asking people for instance to remember the capitals of different states or cities or to remember certain historical facts they will do that at a particular rate but if they've ingested caffeine within the hour prior their ability to recall that information is much much better they are faster and it does not appear that accuracy is reduced in fact in many cases accuracy is enhanced and that's because caffeine both works on the reaction time systems of the brain and body I'll talk about the mechanisms for that in a little bit, but it also stimulates certain neurotransmitters and so-called neuromodulators within the brain and body that give the neural circuits in the brain that are associated with **[0:16:01] Andrew Huberman:** learning and memory a lower threshold to activation. What does that mean? That means that we are better able to access the brain circuitry involved in learning and memory when we have a certain amount of caffeine circulating in our system. So this makes caffeine an incredible performance enhancing compound. And I could give you tens of thousands of examples of this in humans. But before I do that, I want to just touch on what we know about the existence of caffeine in nature and what the existence of caffeine in nature and its effects on other animals tells us about what caffeine does in humans. **[0:16:36] Andrew Huberman:** Because, as I alluded to earlier, what caffeine is doing for us is not just making us more alert, improving our memory, improving our reaction time, and so on. It's actually acting as a powerful reinforcer of experience. And it's acting as not just a powerful reinforcer of the caffeine containing drink that we drink, but also the mug that it's contained in, plus the person that we might be sitting across from when we consume that caffeine, and so on and so forth. **[0:17:07] Andrew Huberman:** If it's a little bit hard for you to conceptualize what a reinforcer is and why I'm calling it a reinforcer, let me spell it out in three specific ways. We often hear about the word reward and we think okay if we do certain things and we like the outcome then those certain things are rewarded right if we're doing something we receive praise the praise is the reward and therefore we are more likely to do that thing in the future in fact a lot of parenting is like that uh and a lot of life is like that however when we hear the word reward we often think about something that feels good to us and certainly if we've worked hard and **[0:17:44] Andrew Huberman:** we get some praise that's natural for the praise to feel good to us Or for instance if we uh we work very hard and we get a certain outcome a trophy a financial outcome a degree outcome recognition etc all of those can act as rewards but those are all conscious rewards we are aware that they are happening reinforcers are a little bit different because the word reinforcement can apply to conscious rewards of the sort that I just described but there are also many ways in which caffeine stimulates the release of chemicals in our body that act as reinforcers but those reinforcers are subconscious That is, we are not aware that they cause this preference for the activities that cause their **[0:18:28] Andrew Huberman:** release. So the study I'm about to describe, beautifully, I believe, encapsulates how is it that humans came to consume caffeine and why caffeine exists in nature, and the powerful effects of caffeine as a reinforcing agent, both in animals, insects, and in you and me. And the title of the paper is caffeine in floral nectar enhances a pollinator's memory of reward. Keep in mind that caffeine is made from plants. Some of you will say, duh, but I think some of us don't realize that the reason why there is caffeine in coffee is because coffee comes from a plant, it's a coffee bean. **[0:19:02] Andrew Huberman:** Certain teas, which of course are plants that people brew, caffeine is contained in those teas, such as yerba mate. Well, why would this bitter substance, because, in fact, caffeine is quite bitter in high concentrations. Why would this bitter substance be something that insects or animals would want to consume at all? It turns out that in most plants, caffeine is present in small enough quantities that insects and other animals, and in fact, we can't actually taste the caffeine. **[0:19:30] Andrew Huberman:** If I were to give you a little bit of pure caffeine, yes, it would be a stimulant for you, but you would say that it tasted awful. It's in a category of compounds that would strongly stimulate the bitter receptors on your tongue and would make you cringe and pucker and essentially walk away from whatever it is that contain that caffeine and from the experience that contain that caffeine. Well, in nature, caffeine is present in very low concentrations or is masked by other flavors within flowers, beans, and plants. **[0:20:02] Andrew Huberman:** And what this paper really points to is that caffeine in nature is acting as a reinforcer for bees that are consuming different nectar. So the way that it works is that bees, of course, go from flower to flower, and they are consuming the nectar. They are bringing nectar and pollen back to the hive, and that provides critical nourishment for the bee colony. The bees are foraging in a way that includes information about color, in particular ultraviolet color, things that we can't see, but they can see because they have different photoreceptors than we do. **[0:20:36] Andrew Huberman:** And what this study shows is that plants and nectars that contain very small amounts of caffeine are the preferred sources of food for bees. And the study is beautiful because they were able to confirm that they could mask the caffeine taste, so it's they know that the bees are not preferring the taste of caffeine. But what they do is they pair caffeine with different food sources for the bees, then they remove the caffeine, and what they find is that the bees very strongly prefer flavors that contain caffeine, not because they could taste the caffeine, but rather for the way that those caffeine containing flavors made the bees feel. **[0:21:16] Andrew Huberman:** So, how do those caffeine containing flavors make the bees feel? The same way that they make you and I feel a little bit more alert and thereby able to do more work for the bee, the more work is the consumption of more food, which then has a further reinforcing effect. So what we're really talking about here is the fact that a caffeine exists in nature in plants. It exists in concentrations that are very low, so low, in fact, that they are not detectable to the taste receptors of insects, and in many cases to the taste receptors of humans. **[0:21:49] Andrew Huberman:** And of course, there can be high levels of caffeine in a plant, but if the plant also contains compounds that mask the flavor of caffeine, well, then those plants are going to essentially be even stronger reinforcers for the flavor of the plant. Okay, so now we're talking about strong flavors plus strong neurostimulant effects of caffeine. And the most important point here is that all of these effects of caffeine are subconscious. It is not because the bee or you likes the taste of caffeine. **[0:22:20] Andrew Huberman:** In fact, most people, when they take their first sip of coffee, they find that it tastes bitter and kind of noxious. They don't like it. You may not even remember that because it happened so long ago, and because caffeine is such a strong reinforcer that very quickly you come to like the taste of coffee. You might even come to like the feeling of your mug in your hand. You might even come to like the smell of coffee, and so on and so forth. **[0:22:44] Andrew Huberman:** And that's because caffeine stimulates the release of certain neurochemicals in the brain, in particular dopamine and acetylcholine, two neuromodulators that increase our focus and alertness and our feelings of well-being. A little bit later, I'll tell you that caffeine stimulates the release of dopamine in a way that's very much distinct from the classical dopamine pathway associated with addiction and reward. In fact, we can think of caffeine as having a somewhat privileged access to the reward systems. I'll give you a bit of a hint of where this is going. **[0:23:14] Andrew Huberman:** Caffeine stimulates the release of dopamine and acetylcholine, not within the classic so-called mesolimbic reward pathway. That's just fancy nerd speak for the reward pathways of the brain. They're associated with things like sex and food and drugs of abuse like cocaine and methamphetamine, but rather caffeine seems to stimulate the release of dopamine in the parts of the brain that are associated with alertness and cognition, meaning the forebrain. This is very important. We have multiple dopamine systems in the brain and body, and caffeine seems to stimulate dopamine directly within the components of the brain that are associated with clarity of thought and well-being, but more so clarity of thought. **[0:23:53] Andrew Huberman:** Now, I'm also talking about caffeine as a strong reinforcer in that it makes you feel good overall, and it does, and that suggests that it also taps into the more classic reward pathway. But it does that in a very interesting and frankly almost diabolical way. When we regularly ingest caffeine, it stimulates the increase in dopamine receptors at multiple sites throughout the brain, but in particular within the reward pathways of the brain. So, not the areas of the brain that are associated with focus and clarity of thought and cognition. **[0:24:24] Andrew Huberman:** It does that, but it is also increasing the level of dopamine receptors in the reward pathway. And what that means is that for any dopamine that's released in response to a positive experience, social experience, or any number of the other things that can stimulate dopamine release, there are more receptors, more parking spots, if you will, for that dopamine to arrive at and to exert its increases in mood, increases in motivation, and overall feelings of drive and excitement. **[0:24:55] Andrew Huberman:** So there are four ways that caffeine works that we need to understand. First of all, caffeine acts as a reinforcing agent. It increases the probability that you will return to and engage in a certain activity or consume a certain beverage or food. Second of all, caffeine increases dopamine and acetylcholine, which are both neuromodulators in the forebrain, which helps us improve our ability to think, to modify our rule sets, that is to adjust our strategies for different social situations and mental demands and physical demands. **[0:25:29] Andrew Huberman:** And third, it increases the number and efficacy of dopamine receptors in the reward pathways of the brain. That is, it makes things that would feel pretty good feel even better. And fourth, caffeine acts as an antagonist to adenosine, which offsets the sleepiness that we would otherwise feel from the accumulation of adenosine that occurs as we are awake for more and more hours throughout the day. So let's talk first about caffeine as a reinforcing agent. Again, this was first most beautifully demonstrated in this study on honeybees, where the bees prefer nectars that contain caffeine, and that all makes perfect sense in terms of the ecology of bees and flowers that contain nectar. **[0:26:11] Andrew Huberman:** There's an advantage, at least in terms of adaptation, that the flower benefits because of distribution of things from the flower, which is good for the flowers, and the bees benefit because they're getting food, and so there's a kind of a symbiosis there. But with humans, we're consuming caffeine containing beverages for our sake. I don't think we have it in mind, nor do the bees have it in mind, frankly, that we're trying to preserve the plants that provide the caffeine. **[0:26:34] Andrew Huberman:** I think we would all um suffer, or I should say 90% of adults would suffer greatly if all the caffeine containing uh coffee and tea plants were gone, certainly. But most of us are not consuming coffees and teas and caffeine containing foods because we're thinking about the plants they come from and we want to help those plants. We're thinking about how we want to help ourselves, and yet the point of the reinforcing effects of caffeine are that they are largely subconscious. **[0:26:59] Andrew Huberman:** We are not aware of them. Now, you might say, no, that's not true. When I drink caffeine, it makes me feel really good, so I'm aware that it makes me feel good. In order to illustrate how reinforcement really works, let me give you the counterexample, which would be an aversive agent. So we have reinforcing agents, and we have aversive agents. Let's say that there were compounds in nature that exist in plants that are aversive, and indeed they are. **[0:27:25] Andrew Huberman:** And let's say that these compounds were present at such low concentrations that you couldn't taste them. Let's say you wake up in the morning and you go to your refrigerator and you open it up and you are thirsty, and so you reach for a nice, um, you know, rich red containing beverage in a glass jar. Maybe it looks like um cranberry juice or something of that sort, or even a nice clear glass of water. It looks like a jug of water or a glass of water, and you drink that. **[0:27:49] Andrew Huberman:** Tastes fine to you, maybe even tastes great to you. And then let's say about thirty minutes later, you feel a little queasy, you feel a little off, you feel like going back to sleep. You just don't feel very good. You don't know why, but your nervous system is a predictive machine, and it has a process in which it back integrates, or I should say integrates backwards into your immediate experience that preceded that not so good feeling. **[0:28:17] Andrew Huberman:** We can reliably say that there is a much lower probability that the next day when you wake up that you would reach for that same beverage or for that same container even. And maybe if you're in a novel environment, maybe you're staying in an Airbnb or a hotel or something of that sort. You might even find that you don't really like the kitchen in which you consume that beverage in the first place. Now you don't know why. **[0:28:42] Andrew Huberman:** And unless you got very, very sick the day before, it's unlikely that you would have such a strong response that you would entirely avoid, for instance, water or glass jars containing liquids, etc. Let's say you went back to the refrigerator and you consume beverage again, and you just didn't feel so well. You felt less good than you normally would. Well, even without any ability to taste what's in that beverage, and even without any understanding of what was happening to you at a conscious level, there is a very, very high probability that you will avoid drinking that particular beverage, and certainly at that location and in the same volume in the subsequent days. **[0:29:23] Andrew Huberman:** That's just the way that aversive agents work, and they work by way of activating neurons in the gut that communicate with areas in the brain that give us this feeling of queasiness. And for some of you hearing this, that pathway and that association with times in which you felt queasy and as if you wanted to vomit is so powerful that you might even be feeling some of that symptomology now. For certain people, that's going to be increased salivation, which precedes vomiting. **[0:29:51] Andrew Huberman:** We know that there's a class of neurons in the brain related to an area called area postrema that actually stimulates vomiting. And if I keep talking about this, I'll probably feel like I want to vomit. So I'm going to move on from this in a moment. So when we ingest caffeine containing beverages and foods, it's the exact opposite scenarios to what I just described. Caffeine as a reinforcer makes us feel slightly better or a lot better in the immediate minutes and hours after we ingest it. **[0:30:18] Andrew Huberman:** So it's acting as a reinforcing agent, not just while you're under the effects of caffeine, but for the things that preceded the ingestion of caffeine, which is why you return again and again to caffeine containing beverages such as coffee and tea, or maybe even foods that contain caffeine, even if the taste of those foods is not something that you would otherwise consider especially delicious. In fact, most people when they take their first sip of coffee or tea or other caffeine containing beverage, they find it to be very bitter, and that's not because of the taste of caffeine, it's because of the taste of the beverage itself, independent of caffeine. **[0:30:53] Andrew Huberman:** However, when caffeine is present in there, they come to prefer that taste over most all tastes. In fact, they will, as I mentioned earlier, will invest a lot of financial resources and time and energy to make sure that they get that beverage. What they're trying to make sure is not that they get that taste, but that they get the caffeine. It is that positively reinforcing. And the taste, therefore, takes on new significance, new meaning, and we come to associate it as positive, and in fact, most of us, including myself, love the taste of espresso, love the taste of coffee, love the taste of yerba mate, even if the initial taste, the very first time that we consume that beverage was **[0:31:34] Andrew Huberman:** either neutral or negative, and that is all because of the reinforcing properties of caffeine. And then, of course, there are the more direct actions of caffeine, that is the faster actions of caffeine, and just to list those off again very briefly, so that you have them in mind going forward. Caffeine also increases the release of dopamine and acetylcholine, both of which are neuromodulators in the forebrain, which increases clarity of thought and your ability to rule switch, your ability to move from one context to another and change and understand the rules of engagement, social engagement, physical engagement, mental engagement, and so forth. **[0:32:12] Andrew Huberman:** And as I mentioned before, caffeine also increases the number of dopamine receptors in the reward pathway, such that any good thing that happens to you, any positive experience that you have, will have a more potent effect on your feelings of well-being. And last but certainly not least, caffeine acts as an adenosine antagonist. It reduces your feelings of lethargy and fatigue and your desire to sleep by parking in the receptors for adenosine and not allowing adenosine to have its pro-sleepy, if you will, effects on your brain and body. **[0:32:46] Andrew Huberman:** I'd like to just briefly talk about adenosine and some of its molecular features. And again, if you don't have a background in biology, don't worry, I promise to make this very clear to everyone. First of all, caffeine is what's called a methylxanthine. It's a plant alkaloid. That's why caffeine itself is very bitter. Again, if I were to give you just the tiniest little bit of pure caffeine, you would find it to be extremely aversive. And so these plants that have snuck small enough amounts of caffeine into them or that have masked the flavor of caffeine with other flavors such that bees and humans want to consume them uh while we don't know what plants think um it does seem very **[0:33:24] Andrew Huberman:** diabolical and very clever in that we are seeking out these caffeine containing uh plants beverages and foods even though caffeine itself is this alkaloid that's very very bitter methylxanthine that is caffeine binds to adenosine receptors and there are really two types of adenosine receptors There are these so-called A one receptors and the A two receptors, and they are present in different parts of the brain and body at different levels. We don't have to get too far into receptor subtypes. **[0:33:53] Andrew Huberman:** More importantly to understand is that adenosine makes us feel tired because of the way that it taps into the ATP pathway. The ATP pathway is central to energy production and feelings of overall energy in our brain and body in all cells and organ systems. When caffeine binds to adenosine receptors, it prevents adenosine from breaking down certain components of the energy production pathway, and the net consequence of that is increased cyclic AMP. So basically, when we ingest caffeine, we are biasing our system towards the pro-energetic aspects of these cellular pathways. **[0:34:33] Andrew Huberman:** Now it's really important to understand that in biology, even if you block a receptor or you prevent the activity of an enzyme, and at least in this case, you end up with more cyclic AMP, more energy. You're not really getting more energy. You're actually borrowing energy against an overall system that is frankly non-negotiable. What do I mean by that? Well, let's say that you were to wake up after six or eight hours of sleep and to drink a lot of caffeine and keep drinking caffeine throughout the day, throughout the day, blocking those adenosine receptors. **[0:35:06] Andrew Huberman:** Yes, you'll offset fatigue, you'll offset sleepiness because that adenosine simply can't function. But at the point where the caffeine becomes dislodged from the adenosine receptors, you will have a massive glut, a backlog of adenosine, and you will feel extra extra sleepy. So, really, there's no way to create more energy in your system. Really, what you're doing is you're changing the timing in which the sleepy signals and the more energetic signals are arriving. And this is really important to understand as the backdrop to the various tools that we're going to get into next, in which you can use caffeine for enhancing mental performance and physical performance and other aspects of health. **[0:35:48] Andrew Huberman:** But it's very important to understand this concept that when you wake up in the morning provided that you slept well and enough the night before your levels of adenosine will be about as low as they will ever be Actually in order to get your adenosine levels really bottomed out you want to avoid caffeine in the first ninety to 120 minutes after waking We'll talk about why that is because it turns out there's a way to completely clear adenosine out of your system in the hour or so after waking But for most people adenosine levels are going to be close to their lowest after a good night's sleep But there's really no negotiating the accumulation of adenosine that's going **[0:36:27] Andrew Huberman:** to occur and going to bias you towards feeling more sleepy than you would otherwise that's going to occur throughout the day. There's really no way to eliminate adenosine. All you can really do is block its function. So it's sort of like borrowing energy against the fatigue that you will inevitably feel. Now, this actually has very important socio-economical relevance. Before caffeine was regularly consumed by human beings, we were really slaves to the light dark cycle. And this was especially true before the presence of artificial lighting. **[0:36:59] Andrew Huberman:** But even before the advent of artificial lighting, humans were largely constrained to the outside light dark cycle. We need to be active during the day and working during the day, and we need to be asleep at night. Caffeine allows us to divorce ourselves from that circadian cycle. Circadian just means about twenty four hours. Caffeine allows us to do that at least somewhat by way of increasing our alertness, that is, spiking our alertness at various times throughout the day and even at night. **[0:37:26] Andrew Huberman:** This is how we can have shift workers, for instance, that can sleep during the day and then drink a strong cup of coffee at eight p. m. and then work into the night. That ability completely transformed our society. Now, of course, the healthiest schedule, we know this with certainty. The healthiest schedule for brain and body is going to be to be alert during the daytime and asleep at night. There's no question about that. Shift workers run into all sorts of health problems. **[0:37:50] Andrew Huberman:** And thank you, shift workers, for doing the important work that you do. We need you. Air traffic controllers, paramedics, firefighters, police officers, etc. But we know that there are serious health consequences, negative health consequences, that is for shift workers. But for most people out there, about 95% of people follow a typical schedule where they're awake during the day and asleep at night. And yet it used to be before the advent of caffeine containing beverages that if you were sleepy in the afternoon, you either had to take a nap or battle that sleepiness, that your activity rhythms and your sleep rhythms were governed by these circadian changes in availability of sunlight and when you slept, and you just didn't **[0:38:32] Andrew Huberman:** have the ability to ingest a beverage that would increase your levels of alertness because you block adenosine. So this is important to understand that nowadays we certainly live in a time in which we use in fact 90% or more of adults and half or more of adolescents and teenagers use caffeine as a way to negotiate with to borrow against this natural pattern of adenosine making us sleepy but again you're just offsetting the effects of sleepiness that adenosine causes you can't eliminate the adenosine entirely the important point is that adenosine as a pro-sleepy molecule is a non-negotiable aspect of your biology In fact, it's so non-negotiable that every twenty four hours you are going to release adenosine and you're going **[0:39:16] Andrew Huberman:** to release adenosine in direct proportion to how long you've been awake. So the longer you've been awake, the more adenosine circulating in your system. There are really only a handful of ways to completely clear out adenosine. The major one being to get sleep. The other is to take a short nap, which of course is sleep, but it's shallow sleep, or non-sleep deep rest, so-called NSDR has been shown to reduce levels of adenosine. And there are certain things such as viewing morning sunlight which because of its effects on cortisol can quote unquote clear out adenosine we'll talk about this in more detail in a few minutes and there's also evidence that certain forms of exercise provided that it's brief and intense **[0:39:58] Andrew Huberman:** can also reduce adenosine not just block its effects now that we've talked about some of the incredible mechanisms by which caffeine changes our experience of life increases alertness and mood etc I want to talk about the use of caffeine as a tool Now, caffeine is a very potent and useful tool for enhancing mental health, physical health, and performance. But there are certain considerations one has to keep in mind, in particular, dose. Now, first off, not everybody will respond to the same dose of caffeine the same way, but we can reliably say that your body weight is a good measure by which you can estimate what a healthy, useful dose of caffeine would be. **[0:40:39] Andrew Huberman:** So for most people ingesting one to three milligrams of caffeine per kilogram of body weight is going to be the range in which caffeine can have positive effects without making us feel overly anxious and give us that feeling that you know we're jumping out of our skin and turn the otherwise positive experience of caffeine into an aversive one For those of you that aren't familiar with thinking in terms of kilograms and normally think in pounds I'll just quickly give you some general estimations that for instance one hundred kilograms equals 220 pounds So for me, I weigh one hundred kilograms. **[0:41:17] Andrew Huberman:** That means that one to three milligrams, again, milligrams, thousandth of a gram, one to three milligrams of caffeine per kilogram of body weight would mean for me, I could safely ingest one hundred to 300 milligrams of caffeine in a single dose, in a single drink, if that's the way I'm consuming it, or pill form, if that's the way that I'm consuming it. And it's very likely that that will be a tolerable dose. However, if you are not somebody that's accustomed to drinking caffeine on a regular basis, I suggest you start on the lower end of that one to three milligrams per kilogram of body weight range. **[0:41:56] Andrew Huberman:** So, for instance, if you're somebody who weighs fifty kilograms, that's approximately 110 pounds, and you would be pretty comfortable ingesting somewhere between fifty and one hundred fifty milligrams of caffeine. So what I recommend is that people who are considering using caffeine as a tool or who are already ingesting caffeine start to think about the dosage of caffeine that you are ingesting or plan to ingest and the timing in which you ingest that caffeine relative to certain tasks throughout your day, your waking and your sleep. **[0:42:26] Andrew Huberman:** And we'll talk about that in just a moment. But the first step for you is to figure out how much you weigh in kilograms, and then to go to that number of one to three milligrams of caffeine per kilogram of body weight, and that's a good range in which you might want to explore the use of caffeine in a single application, meaning a single dose. Now I do realize that some people out there are drinking coffee all day long or having coffee in the morning and then again in the afternoon. **[0:42:55] Andrew Huberman:** What I'm referring to here is the ingestion of caffeine in a single bout right. One cup of coffee or two cups of coffee for instance to achieve that one hundred to 300 milligram range if that's what's appropriate for your body weight. But to avoid any confusion when I talk about dosage of caffeine what I'm really talking about is not the total amount of caffeine ingested per day. I'm talking about the total amount of caffeine ingested in one sitting or setting. **[0:43:21] Andrew Huberman:** That is, and if you're somebody who's drinking caffeine multiple times throughout the day, you could imagine, for instance, let's say the appropriate dose for you in order to get an enhancement in mental performance or physical performance is 200 milligrams, and you are somebody who's doing some work in the morning and you want to have that lift in the morning to be able to focus better, and you're doing some physical exercise in the afternoon or vice versa, that you would ingest 200 milligrams of caffeine at two separate times per day, separated by about four hours. **[0:43:51] Andrew Huberman:** Now you don't have to separate them. You could, uh, you could put them two hours apart, for instance, but we'll talk about half life of caffeine and so forth. Just keep in mind that if you're ingesting 200 milligrams of caffeine, and that's the appropriate dose for you based on your body weight, and then you are ingesting another 200 milligrams of caffeine an hour later, you are effectively ingesting approximately 400 milligrams of caffeine, which is going to start exceeding the dose in which you can normally tolerate without feeling anxious and jittery. **[0:44:20] Andrew Huberman:** With all of that said, there is a range of tolerance for caffeine that's based on two things. One is a pre-existing disposition, that is whether or not your genetics and nervous system and the backdrop of your life, how much stress you're experiencing tends to make you feel more anxious and alert and jittery before you ingest any caffeine. And the other is how so-called caffeine adapted you are. We often hear about tolerance. Tolerance means something very specific. **[0:44:43] Andrew Huberman:** It's the ability to ingest more and more of something with a plateau that is a non-increase or an actual reduction in the effectiveness of that thing. But here we're not really talking about tolerance to caffeine. What we're talking about is being caffeine adapted. A simple way to understand whether or not you're caffeine adapted or not is that if you drink caffeine and it tends to increase your heart rate and make you feel more alert and a bit more anxious, then chances are you are not caffeine adapted, provided the amount of caffeine is within the healthy range for you. **[0:45:13] Andrew Huberman:** That is the ranges we talked about a moment ago. However, if you're somebody who drinks caffeine and you actually feel alert and relaxed, chances are you are caffeine adapted. And so at various times during today's episode, I'll talk about people who are caffeine adapted and people who are not caffeine adapted. We'll talk about the use of caffeine every other day. I know a few habitual caffeine drinkers, including myself, just the simple mention of that probably sounds aversive. **[0:45:37] Andrew Huberman:** Um, but there is actually great utility to using caffeine every other day as opposed to every day. But just keep in mind that some people will drink caffeine and not get much of a lift from it at all. Other people will drink caffeine and they will feel extremely anxious, even at dosages far lower than that one to three milligrams per kilogram of body weight range that I described a moment ago. So you have to take into account individual differences. **[0:46:02] Andrew Huberman:** That said, one to three milligrams of caffeine per kilogram of body weight for a given sitting, you know, for your morning coffee or your mo or your morning yerba mate tea, is a good range from which to start. And I do encourage you to go online and look up the various beverages and foods that you might be eating that contain caffeine. For instance, some people are surprised to discover that the coffee that they get from some of the more standard popular vendors out there, the small coffee or the medium coffee, for instance, can contain as much as 400 to 600 milligrams of caffeine, and that the large coffee that is often sold at those commercial vendors can contain **[0:46:42] Andrew Huberman:** as much as one gram, one thousand milligrams of caffeine. Now, you may be adapted to that such that it doesn't make you feel anxious. But if you wonder why you feel irritable and you get a headache when you don't get that caffeine or that amount of caffeine at precisely the time that you're used to getting it each day that's because you are consuming quite large quantities of caffeine on a regular basis So I do recommend whether or not you drink soda or coffee or tea that you figure out the source of that okay So figure out what vendor you purchase it from what kind of coffee and go online and spend a little bit of time because the information is **[0:47:20] Andrew Huberman:** out there to discover what levels of caffeine you're actually ingesting Now if you happen to be ingesting more than one to three milligrams per kilogram of body weight of caffeine that's not necessarily bad However you do want to be careful about ingesting very high levels of caffeine over long periods of time in your life because there can be issues that start to arise In particular a bias towards higher levels of anxiety and depletion of certain electrolytes because caffeine is a diuretic can cause you to lose sodium and other and other things of that sort And also just from simply a dependent standpoint it does appear that if you ingest high levels of caffeine that is exceeding the dosages that normally **[0:48:02] Andrew Huberman:** you could get away with and get just as much mental enhancing and physical enhancing benefits that you can cause some disruption to the microvasculature you can bias yourself towards headaches anxiety attacks and it you can become actually quite irritable when you're not getting those higher levels of caffeine So I do encourage you to figure out not just what an appropriate caffeine dosage would be for you, but also how much caffeine you might already be ingesting. The first tool I'd like to talk about is one that I've mentioned before on this podcast several times. **[0:48:33] Andrew Huberman:** And it's something that, if you haven't heard of, will be very useful to you. And if you have heard this tool before, I'm going to add some additional features to the description of this tool that should make this worthwhile for you as well. And that is to delay your caffeine intake to ninety to 120 minutes after waking up on most days. And I'll be very clear as to days in which you might want to ingest caffeine more closely to when you wake up. **[0:49:01] Andrew Huberman:** Why would you want to delay your caffeine intake to ninety to 120 minutes after waking? The answer to that is very simple. Many people wake up in the morning, they drink caffeine within ten, twenty, thirty, sometimes within two minutes of waking, and they feel more alert, naturally. That makes sense because of the effects of caffeine in blocking the effects of adenosine that I talked about earlier and its effects on other neurotransmitter systems. But then what they find is that in the early afternoon, in particular after lunch, they experience a dramatic dip in their overall levels of energy, the so-called afternoon crash. **[0:49:39] Andrew Huberman:** And in most cases, the way they respond to that is to ingest more caffeine, which indeed can increase their levels of mood and alertness. However, as we'll soon talk about, there is a problem with ingesting caffeine in the afternoon if it falls within eight or ten or dare I even say twelve hours of going to sleep, and that is the caffeine ingested in the afternoon for most everybody, I'd say for ninety five plus percent of people, disrupts the architecture and quality of their nighttime sleep. **[0:50:12] Andrew Huberman:** And I should say that it doesn't necessarily impact their ability to fall asleep and maybe even sleep through the night, but that the depth and quality of that sleep is disrupted by consuming caffeine in the afternoon. A little bit later, I'll talk about how you can offset some of those negative effects if you absolutely require caffeine in the afternoon. But there's a huge advantage to restricting your caffeine intake to the early part of your day, but not consuming caffeine within the first ninety to 120 minutes after waking. **[0:50:40] Andrew Huberman:** In fact, many people find that if they delay their caffeine intake to ninety to 120 minutes after waking up, that they feel more alert in the morning and they completely avoid that afternoon crash. Now, that said, many people, including myself, do need a short nap or non-sleep deep rest or other form of relaxation for ten to thirty minutes in the afternoon. That is natural and healthy. I'm not referring to the need for that when I refer to the so-called afternoon crash. **[0:51:10] Andrew Huberman:** What I'm talking about in the afternoon crash is an inability to recover energy and focus and a need to consume more caffeine just to make it through the afternoon. By delaying caffeine intake from to ninety to 120 minutes after waking, there are a couple of things that are accomplished. First of all, you offset that afternoon crash, and this is an effect that many people experience the very first time they start delaying their caffeine intake to ninety to 120 minutes after waking. **[0:51:36] Andrew Huberman:** And the reason this works so well is the following. As I mentioned earlier, adenosine is a molecule that builds up the longer that we are awake. It is a molecule that is reduced or cleared from our system by sleep. So when we emerge from sleep, regardless of how long we've slept, our adenosine levels are lower than they were when we went to sleep the previous night. If you slept well enough and long enough, those adenosine levels can be very, very low, but they are never completely zero. **[0:52:09] Andrew Huberman:** When you wake up in the morning, even if you're one of these people that springs out of bed and is ready to attack the day, and here I'm certainly not explaining myself. I'm not not one of those people. I tend to wake fairly slowly. But if you're one of those spring up and attack the day, or you're one of the people who moves more slowly into your day, regardless, there's still some residual adenosine in your system. **[0:52:31] Andrew Huberman:** And this is particularly the case if you did not get enough sleep or enough depth of sleep the night before, the correct ratios of slow wave sleep and rapid eye movement sleep. And for those of you interested in optimizing sleep, I'll just refer you to our master your sleep episode of the Huberman Lab podcast, the Perfect Your Sleep episode of the Huberman Lab podcast, and we have a toolkit for sleep, all of which are available zero cost, timestamped, etc. **[0:52:53] Andrew Huberman:** at hubermanlab dot com. You wake up in the morning and your adenosine levels are low, but they're not zero. And if you didn't sleep that well or deeply enough the night before, you're going to have more adenosine in your system. You might think the logical thing to do is therefore to drink caffeine and to block the adenosine that's there. But what happens if you do that is there's an accumulation, a sort of glut of adenosine that hangs around, and then in the afternoon, when the effects of that caffeine start to wear off, you will experience the so-called afternoon crash. **[0:53:28] Andrew Huberman:** As I mentioned earlier, there is a way to clear out the adenosine that's present when you wake up in the morning and to clear it out essentially completely without just blocking its receptors and letting it accumulate or hang around. And the way to do that is to deliberately spike your cortisol. Now, many of you have heard of cortisol, the so-called stress hormone, as a bad thing, and indeed, chronically elevated cortisol is a bad thing. It depletes your immune system, it's bad for psychosocial effects, it tends to make us feel anxious, and on and on. **[0:54:02] Andrew Huberman:** But cortisol itself is not bad. Cortisol is wonderful. Cortisol enhances the efficiency of the immune system. It makes us alert and focused. It stimulates our metabolism. It does a huge number of positive things, provided that it is released in a circadian fashion, that is at the appropriate times every twenty four hours, and that it tends to peak very close to waking. In fact, one of the reasons you wake up in the morning, assuming that you weren't woken up by some noise or or sleeping in an environment that's too warm, etcetera, is that your cortisol levels start to rise. **[0:54:34] Andrew Huberman:** And shortly after waking, your cortisol levels will start to reach their peak. And when I refer to a cortisol pulse, that's just, I mean, biology nerd speak for a rise and peak in cortisol. You want that cortisol pulse to occur early in the day, close to waking, and you want that for a couple of reasons. First of all, if you don't restrict that cortisol pulse to early in the day, it will tend to bleed into the later parts of the day. **[0:55:00] Andrew Huberman:** And actually, a late shifted cortisol peak is one of the hallmark signatures of depression, low-level depression, and serious depression. And it can start to disrupt sleep and certainly can disrupt mood, metabolism, and your immune system. So you want that cortisol peak early in the day. How do you ensure that that happens? Well, you wake up in the morning, and whether or not you're a bounce out of bed type or you're more groggy, you know, kind of wade slowly into the day type, like I am, you wake up and you don't ingest caffeine. **[0:55:29] Andrew Huberman:** Gr- fine, and in fact, beneficial to hydrate with water and electrolytes. Terrific, in fact, I would say necessary to get bright light in your eyes, ideally from sunlight. I've talked about this many, many times before on the podcast. If you wake up before the sun comes out, then turn on bright artificial lights. But then certainly once the sun is out, and even on cloudy days, in fact, in especially on cloudy days, get outside for anywhere from five to twenty, maybe even thirty minutes. **[0:55:55] Andrew Huberman:** Do some work outside, take your breakfast outside if you're a breakfast eater. Get something done outside, even if it's just to get outside and get bright light in your eyes. Why? Well, because it's been shown in studies on humans that getting bright light in your eyes in the first hour after waking, or as soon as possible after waking, increases the peak of that cortisol pulse by 50%, five, zero. And that cortisol pulse, yes, increases mood, yes, increases alertness, but it does one other very important thing, which is that that through an indirect pathway, it can clear out any residual adenosine that might be present in your system when you wake up in the morning. **[0:56:35] Andrew Huberman:** Again, this is going to be especially important for those of you that are not getting as much sleep or as much quality sleep as you would like. It's going to be very important for you to get that morning bright light, ideally from sunlight, get that cortisol peak going. Other ways to increase that cortisol peak would be to do some physical activity. If you don't have time to do a full workout, well, then getting some movement, you know, ten minutes of skipping rope, or even five minutes of skipping rope, or jumping jacks, or walking, if that's all you have time for, ideally while getting the sunlight in your eyes. **[0:57:05] Andrew Huberman:** But that's going to zero out the adenosine present in your system. If, however, you were to wake up and immediately drink caffeine, caffeine itself can stimulate the release of cortisol a little bit more than it would otherwise be present in your system. But by blocking those adenosine receptors, and because of the indirect effects of caffeine on the cortisol system, you actually are reducing the clearance of adenosine that would otherwise occur. So I realize that's a mouthful. **[0:57:37] Andrew Huberman:** Just to be very clear, if you wake up and you ingest caffeine right away, you're blocking the adenosine receptor, but you're not clearing it out. You're also preventing cortisol from having its normal increase and rise such that it can directly clear out adenosine because cortisol can clear out adenosine, and that's what you want. You want to be at maximum alertness and focus in your morning and throughout your day. And by delaying your caffeine to ninety to 120 minutes after waking, you set up your system so that you get that morning cortisol peak, ideally a peak that's even greater because you're getting your bright light viewing. **[0:58:14] Andrew Huberman:** And then when you ingest your caffeine ninety to 120 minutes after waking, not only will you be craving it just a little bit, but you will be drinking that caffeine on an already existing backdrop of increased alertness for two reasons. One is adenosine is zeroed out, and your cortisol peak is higher. And so now when you ingest caffeine, you can actually ingest levels of caffeine that are a little more reasonable that almost with certainty are going to fall in this one to three milligrams per kilogram dosage, and will allow you to feel really alert, and will carry that alertness well into the afternoon hours without the need to drink more caffeine, and thereby will prevent you from drinking **[0:58:58] Andrew Huberman:** caffeine and disrupting your nighttime sleep. And, of course, by getting better nighttime sleep, you're going to zero out your adenosine even more. So what I'm describing here are essentially two tools. I'm telling you to get morning sunlight and maybe some exercise in conjunction with that, even if it's brief exercise. But the main tool of delaying caffeine ninety to 120 minutes after waking has immediate effects, but it also sets in motion a cascade or domino falls that lead to better sleep and more wakefulness the next night and the next day and so on and so forth. **[0:59:32] Andrew Huberman:** Now I realize there are some people who just simply cannot or will not delay their caffeine ninety to 120 minutes after waking for whatever reason. First off, let me say that if you are somebody who likes to wake up and do very intense exercise within the first ninety minutes after waking, well, in that case, it would be appropriate to ingest your caffeine just prior to doing that exercise. Not a problem, not a problem. But you should expect that the combination of drinking caffeine very shortly after waking, plus exercising very intensely shortly after waking will increase the intensity of that early afternoon and afternoon fatigue that you feel. **[1:00:08] Andrew Huberman:** Now, for some people, that's a great thing. They can afford to take a nap or do non-sleep deep rest, step away from work, and so forth. In that case, I strongly encourage you to do whatever it is that allows you to get regular exercise, because regular exercise is going to be very beneficial. In fact, we did an entire episode called Toolkit for Fitness that describes a couple of different, but really one main structure that allows you to get the appropriate amount of resistance training and cardiovascular training and flexibility training throughout the week. **[1:00:37] Andrew Huberman:** I happen to follow that program, and it works very well. And it does involve some of those workouts to come very early in the morning, shortly after waking. And in those cases, I do ingest caffeine just prior to those, so within, you know, ten, twenty minutes of waking. However, on other days, I personally delay my caffeine intake ninety to 120 minutes, and I've done that to great benefit. And most people, if not all people that try that, have reported the same. **[1:01:03] Andrew Huberman:** I should mention that some people will find getting out to that ninety minutes to be excruciatingly difficult because they're so accustomed to ingesting caffeine close to waking up. In that case, maybe just push out your caffeine intake by about fifteen minutes each day until you hit that ninety to 120 minute mark, and that will make it much easier. It might take you a week or so to get there, but once you get there, you'll find it to be quite easy to maintain. **[1:01:25] Andrew Huberman:** The other thing is that if you are somebody who insists on drinking caffeine very shortly after waking, I would encourage you to drink half of your caffeine then, and then the other half of your caffeine about an hour later. That also will help offset some of the afternoon crash for reasons related to the so-called kinetics of caffeine. Caffeine has a quarter life of about twelve hours. That means that if you were to ingest a cup of coffee at, uh, let's say eight a m, and let's say a hundred milligram coffee, just for sake of, uh, simplicity, that about 25% of of that caffeine action, we wouldn't really say twenty five milligrams, but about 25% of that **[1:02:02] Andrew Huberman:** caffeine action will still be present at eight p m. That night, which is pretty remarkable. So there's a long arc of caffeine effects, and this is why it can impede sleep if it's, uh, if we take caffeine in the afternoon. But again, if you're somebody who wakes up and you really need caffeine right away, and you refuse to do this ninety to 120 minute delay thing that I'm talking about, well, then, in that case, I would drink half of your caffeine upon waking, and then a little bit more, or ha, or the other half about an hour later. **[1:02:31] Andrew Huberman:** And that will extend the arc of that caffeine effects such that you don't need it again in the afternoon because you won't experience the afternoon crash. Because of the way caffeine works, I should mention that if you ingest caffeine on an empty stomach, it will have a more potent stimulant effect. That will also tend to increase the level of jitteriness that caffeine can produce. Later, I'll talk about ways to offset that jitteriness, but I'll just tell you one tool now. **[1:02:56] Andrew Huberman:** Many people opt to take one hundred milligrams of theanine, T-H-E-A-N-I-N-e, theanine, as a way to offset some of that jitteriness. Theanine will reduce the jitteriness of caffeine, which is why many energy drink manufacturers, and even some coffee manufacturers are now putting theanine in energy drinks and in ground coffee. Because, no surprise, it allows people to consume more of that beverage, and thereby purchase more of that beverage, which is what these vendors want, without feeling overly anxious and jittery. **[1:03:27] Andrew Huberman:** So you can take pill form theanine if you want with your caffeine. I don't tend to do that, rather, I control the total dosage of my caffeine. I do tend to consume caffeine on an empty stomach because I do restrict my caffeine intake to the early part of the day. And I generally eat my first meal somewhere around eleven a m, and then I generally eat my last meal sometime around eight p m or so. Those are those are averages, I would say, plus or minus an hour. **[1:03:51] Andrew Huberman:** And that's not because I'm religiously following any kind of, um, time-restricted feeding. It's just, though, that's tends to work best with my schedule and my appetite. But again, that's a general theme. There are days in which I wake up and I'm very hungry, and I might ingest something, um, a small snack or something. Or if I'm meeting somebody for breakfast, sometimes I'll have breakfast, sometimes I won't, and so on and so forth. The point is that you can get away with drinking less caffeine to get the stimulant effect if you do it on an empty stomach. **[1:04:20] Andrew Huberman:** And if you're somebody who likes to exercise on an empty stomach, and I'm one of those people, well, then ingesting caffeine just prior to exercise can be a fantastic tool. A little bit later, we'll talk about some of the physical performance enhancing effects of caffeine, but I'll just briefly jump to a point about that as we relate to morning exercise. If you are somebody who regularly ingests caffeine and we can define regularly by if you've ingested caffeine every day for the last two weeks you're a regular consumer of caffeine whereas if you're somebody who only ingests caffeine somewhere between two and four times per week well then you are not a regular consumer of caffeine you're an intermittent user of **[1:05:02] Andrew Huberman:** caffeine Well, if you're somebody who's a regular user of caffeine, the performance enhancing effects of caffeine are going to be most dramatic if you take two or three days off from drinking caffeine, which to my mind, as a, uh, I don't want to call myself a caffeine addict, but a regular caffeine user, that's a horrible notion to me, a disersive notion, um, because I do like the effects of caffeine so much. But if you really want to see the maximum performance enhancing effects of caffeine, you'll do either one of two things. **[1:05:29] Andrew Huberman:** You will either abstain from caffeine for a few days or three days prior to ingesting caffeine, or you will use caffeine on an empty stomach. It's very clear that caffeine on an empty stomach enhances both the mental and physical enhancing effects of caffeine. And, of course, all of that has to be stated on the backdrop of consideration that if you, uh, you know, you're very, very hungry, it can be make it hard to concentrate, and so on, and so forth. **[1:05:54] Andrew Huberman:** So I'm not encouraging people to starve themselves, um, by any means. Uh, certainly don't do that. But if you want to maximize the performance-enhancing effects of caffeine, you will consume it on an empty stomach. And then, as a final point to that, caffeine is a diuretic. It causes us to lose fluid, and along with that fluid, to excrete sodium because of the effects of caffeine on various processes within the kidney. So one thing that works very well to maintain mood and alertness longer, given a certain amount of caffeine intake, and to avoid the jitteriness and and what can sometimes feel like a crash or low blood sugar feeling or even blurry vision, is to make sure that you consume at **[1:06:33] Andrew Huberman:** least an equal volume of water with your caffeine. And ideally, that water would contain maybe a small pinch of salt or some sort of electrolyte drink, uh, or powder rather. For me, I use LMNT. Full disclosure, they are a podcast affiliate and sponsor, but you don't need to do that. You could simply just have a glass of water alongside your your coffee or espresso or your yerba mate and just put a small pinch of sea salt in that, or even just plain table salt, and that will help offset some of the jitteriness of caffeine. **[1:07:01] Andrew Huberman:** A lot of people think that when they ingest caffeine, they get the jitteriness and crash because their blood sugar is low. And while that can be the case, oftentimes it's simply because of the excretion of sodium that's occurred when they've ingested caffeine. So I encourage you to hydrate well and to hydrate with something that contains a little bit of sodium. Obviously, not so much that it increases hypertension or something of that sort, but a small amount of sodium or an electrolyte drink like LMNT, and there are other, uh, electrolyte drinks out there that can accomplish the same, of course. **[1:07:28] Andrew Huberman:** Just a couple of quick notes about theanine, because there are a growing number of products out there that contain theanine, and there's certainly a growing number of people out there who are using theanine for the effect that I described before, which is to offset some of the jitteriness associated with caffeine containing beverages or foods. And of course, I should mention that I've talked about the effects of theanine on sleep. Uh, at that sleep toolkit that you can find as a free download, you don't even have to sign up for anything. **[1:07:55] Andrew Huberman:** You can just download it from Huberman Lab dot com, go to the menu, go to newsletter, you'll see the toolkit for sleep. You'll see that the so-called sleep stack that, uh, I use and recommend includes magnesium threonate, something called apigenin and theanine. Although that sleep stack is designed to be taken thirty to sixty minutes prior to sleep, and I make the point there, and I'll make it again here, that ingesting theanine prior to sleep is not a good idea if you are somebody who tends to have very vivid dreams, night terrors or night walk, uh, sleepwalking, excuse me, etc. **[1:08:29] Andrew Huberman:** In that case, eliminate theanine from from the sleep stack. However, a number of people are using theanine and products are using theanine to offset jitteriness from caffeine containing products during the daytime, daytime consumption, that is. A couple of notes about theanine. Theanine is something that is present in green tea, right? It's now been, uh, created as a supplement. It's what's called a non-protein amino acid. So, while there are amino acids in proteins, there are, of course, amino acids in non proteins, and theanine is one such non-protein amino acid. **[1:08:59] Andrew Huberman:** Theanine tends to stimulate the so-called glutamate and glutamine pathway. It's actually very similar to glutamate and glutamine, and it has a lot of effects on a lot of different aspects of the nervous system. But the general effect of theanine is to compete for the receptors for certain neurotransmitters, and the neurotransmitters I'm referring to are excitatory neurotransmitters, things like glutamate, and they govern a tremendous amount of our daily thinking and action and feeling, etc. Because they're present at so many connections between neurons in the brain. **[1:09:32] Andrew Huberman:** Theanine competes for the receptors for glutamate and tends to reduce our overall levels of alertness. So really, when people take theanine along with caffeine, what they're doing is they're really, uh, taking a slight, I don't want to call it depressant to the point where it misleads people and makes people think that it will make you depressed. The word is a little bit misleading, but tends to reduce or blunt some of the more excitatory, pro-alertness actions of neurons in the brain. **[1:10:01] Andrew Huberman:** So when you take it alongside caffeine, tends to quote unquote even things out a bit. I should mention that the dosages of theanine that are effective for offsetting the jitteriness of caffeine is 200 to 400 milligrams, and the studies that I was able to find showed that essentially up to 900 milligrams per day can be safe, but that's a very high dosage of theanine. In fact, so much so that it might increase sleepiness to the point where it wouldn't feel good. **[1:10:27] Andrew Huberman:** There are also some positive effects of daytime consumption of theanine that are independent of reducing the jitteriness of caffeine. For instance, there's a study demonstrating that seventeen days of ingesting theanine at these 200 to 400 milligram dosage of at one to three times per day can reduce depression and anxiety. There are also some good data out there showing that theanine can have positive effects on endothelial cells, so blood vessels, capillaries, and so on, and increase some of the function of blood vessels, allowing them to pass more blood through them, give them a little bit more elasticity, if you will. **[1:11:03] Andrew Huberman:** So theanine has certain pro-sleep effects if it's taken prior to sleep. It can enhance the quality, depth, and duration of sleep. Again, if you're a sleepwalker or somebody who has extremely vivid dreams from which you wake up in the middle of the night, probably best to leave out theanine, or maybe reduce the dosage down to one hundred milligrams, and if that's still too much, then eliminate it completely. But theanine can be terrific for enhancing quality, depth, and duration of sleep. **[1:11:28] Andrew Huberman:** It can also reduce the jitteriness associated with caffeine containing beverages and foods, and it has certain antidepressant and pro-endothelial effects. That is, it can offset depression, it can offset anxiety, although those are minor effects, okay, subtle effects, and it has been shown to improve endothelial cell, that is vessel and capillary function and structure in ways that can be beneficial for both brain and body. Now, one final point about theanine that's worth paying attention to is that the kinetics of theanine are such that you don't need to take theanine every time you ingest a caffeinated beverage. **[1:12:10] Andrew Huberman:** When we ingest caffeine, the peak effects of caffeine occur about thirty minutes after we drink it. And there I'm assuming one takes it all at once, and this is a key point that we'll come back to later, right? Rather than sipping your coffee slowly over a couple of hours or an hour. If you drink all 200 or 300 milligrams of caffeine in your coffee, or 600 milligrams of your coffee if you're getting one of those commercial coffees, and you take theanine along with it, theanine will block some of the jitteriness and anxiety-inducing effects of caffeine that can occur for much longer than the effects that caffeine lasts. **[1:12:49] Andrew Huberman:** So the peak in theanine occurs about an hour after ingestion. I suppose if you wanted to get really fancy and really dial in the kinetics, you could ingest theanine about half hour before you ingest your caffeine. But I think that's getting a little bit, uh, excessive in terms of controlling your microenvironment, if you will. I think it would be perfectly fine to take a hundred to 200 milligram capsule of theanine along with your coffee or tea or so forth. **[1:13:17] Andrew Huberman:** And just realize that if you drink more caffeine or you extend your caffeine intake over several hours, that you don't necessarily have to take theanine repeated times throughout the day. Let's talk for a moment about when to avoid caffeine. And in the same stroke, let's also talk about some of the myths around caffeine. For instance, one of the major myths around caffeine is that it can increase osteoporosis. Turns out that while there is a relationship, of course, between calcium and osteoporosis, that is reductions in bone density, and it is the case that caffeine can extract calcium from certain tissues. **[1:13:53] Andrew Huberman:** The large scale studies that are out there essentially prove that if people are ingesting enough calcium through their diet, which most everybody is, although certainly there are some people that need to supplement calcium or make it a point to consume more calcium containing foods. But assuming that you are getting adequate levels of calcium, there is no direct relationship between caffeine intake and osteoporosis, at least not that I'm aware of. I know this was debated for a number of years in the literature, but the literature seems to have arrived at a general consensus now that caffeine itself is not going to create or exacerbate osteoporosis, provided people are getting enough calcium through their diet, that is through foods, through supplementation, or **[1:14:40] Andrew Huberman:** both. Some of the other myths around caffeine are that, for instance, caffeine will reduce testosterone levels or will reduce estrogen levels. Other myths out there are an exact opposite to that, that caffeine will increase testosterone levels, in particular free testosterone levels. There have been some large scale studies addressing the hormone effects of caffeine. They are a little bit difficult to do. I should just mention that caveat. And the reason they are difficult to do is because 90% of adults are consuming caffeine. **[1:15:12] Andrew Huberman:** And therefore, you can imagine it's very hard to find a control group to compare the caffeine consumers to, in particular, a control group that's well controlled for other things like lifestyle, diet, exercise, etc. However, when one controls as well as one can for all the various factors that could impact hormones, what one discovers is that caffeine intake, at least at the dosages we talked about earlier, one to three milligrams per kilogram of body weight, or even up to double that, that there are no consistent increases or reductions in testosterone or estrogen in men or women that can be directly attributed to the caffeine intake. **[1:15:57] Andrew Huberman:** And I say directly attributed because in these association studies, one always has to wonder, for instance, if because people are ingesting more caffeine, they have more energy and therefore exercising more, and exercise is known to have effects on testosterone, estrogen, and other hormones, whether or not the effects of caffeine on those hormones is indirect and so on and so forth. And this all just underscores the challenges of doing studies on humans in the wild in their natural habitat of living, as opposed to an acute study, as it's called, of bringing someone into the laboratory and studying them just for those hours or moments. **[1:16:28] Andrew Huberman:** With all that said, there does appear to be a relationship between caffeine intake and so-called sex hormone binding globulin, which is a protein present in the body of both men and women that binds to the sex steroid hormones, testosterone and estrogen, and prevents them from being in their free or active form. It has been shown that ingestion of caffeine, even in the sorts of dosage ranges that are considered safe and that we've been discussing, can increase sex hormone binding globulin, such that it can slightly reduce overall levels of free testosterone and free estradiol in women. **[1:17:08] Andrew Huberman:** Now, those effects are relatively minor, but they do exist. If any of you are interested in reading further into the effects of caffeine on hormones, I'll just refer you to a couple of studies. We will link to this in the show note captions. The title of the study is consumption of caffeinated beverages and serum concentrations of sex steroid hormones in US men. And within this study, there is a reference to a equally sized and powered study done on women, both of which converged on the same conclusion. **[1:17:37] Andrew Huberman:** By examining more than a thousand, so in this case, 1,410 men or more than a thousand women, that there are increases in sex hormone binding globulin associated with increased intake of coffee in particular. But they were able to narrow that down specifically to ingestion of caffeine. So it's not coffee per se that's causing the increase in sex hormone binding globulin, it's actually caffeine itself. Now, again, the increases in sex hormone binding globulin were not so significant that, at least to my mind, they seem like a concern. **[1:18:10] Andrew Huberman:** Although I think that it is worth noting that if you're going to consume caffeine that you probably want to consume caffeine in a way that is in dosages and with the sort of timing that will allow you to get away with ingesting caffeine but not to excess so to derive the benefits of caffeine without for instance driving up sex hormone binding globulin too far now why would that be a good idea why would you want to make sure that you have enough free testosterone and free estrogen Well, some of that is related to the acute effects of those hormones in terms of well-being and, uh, libido and strength and mood, etc. **[1:18:45] Andrew Huberman:** But some of it also relates to the longer-term effects of sex steroid hormones. Many people don't realize this, but the sex steroid hormones operate on the receptors at the surface of cells to have immediate effects, but they also can enter cells and actually go into the nucleus of cells where the DNA of those cells are contained and control gene expression in those cells. So the sex steroid hormones testosterone and estrogen are controlling a lot of different cellular functions over long periods of time so blunting their action over long periods of time is probably not a great idea but again at the dosages of caffeine that we're talking about uh today one to three milligrams per kilogram of body weight uh **[1:19:24] Andrew Huberman:** unlikely that the increases in sex hormone binding globulin that one experiences from that are going to be detrimental And certainly the positive effects of caffeine that one experiences in terms of mental performance and physical performance and the fact that it increases energy to do the sorts of things like exercise that we know can profoundly improve hormone profiles right you know two fold or three fold improvement in hormone profiles when that case it seems that ingesting caffeine is overall a good thing provided it's not in excess That also makes this the appropriate time to mention one of the more impressive effects of caffeine, which is on overall levels of mood and mental health. **[1:20:02] Andrew Huberman:** There are several studies on this, but the one that I'm particularly fond of was published in 2019 in psychiatry research. And the title of the paper is Inverse Association Between Caffeine Intake and Depressive Symptoms in US Adults. And these are data from the National Health and Nutrition Examination Survey. And the basic takeaway is that while of course there are a ton of different factors that are going to relate to whether or not people are depressed or not life circumstances genetics and so on that and here I'm quoting from the study caffeine's psychostimulant properties that just means the ability to make us feel more alert and positive appear to protect against depressive symptoms and of course they acknowledge that additional **[1:20:42] Andrew Huberman:** studies are needed But this is just one of several studies pointing to the fact that people who regularly ingest caffeine in the appropriate dosages do seem to enjoy an antidepressant effect overall. I wouldn't want anyone to consider caffeine a treatment for severe depression, or at least not alone a treatment for severe depression. But provided the anxiety inducing effects of caffeine can be kept in check through use of theanine or making sure that the dosage and the timing of caffeine ingestion is correct, then caffeine overall seems to be good for our mood and prevent depression, or at least keep depression at bay when depression might otherwise surface or be more severe. **[1:21:21] Andrew Huberman:** And of course, there are the don'ts surrounding caffeine intake as it relates to sleep. And to put it very simply, sleep, that is getting enough quality sleep each night is the foundation. It is the bedrock of mental health, physical health, and performance. Sleep and the power of sleep far exceeds any nootropic you could ever take, any prescription drug you could ever take, any health promoting tool for your immune system, your metabolism, your mental function, your physical function you could ever take. **[1:21:52] Andrew Huberman:** Sleep is the bedrock. I know a lot of people experience challenge with sleep. Nobody is perfect about sleep. That's important to keep in mind. I think a good goal is to get enough quality sleep of sufficient duration, 80% of the nights of your life, and then as much as possible to make sure that the remaining 20% of nights, you are not getting enough sleep for good reasons, as opposed to hard reasons. Good reasons would include raising children. **[1:22:16] Andrew Huberman:** That's important. After all, every species desires to make more of itself and to preserve and extend the well-being of its young. So child rearing is a perfectly legitimate reason to get a lack of sleep. But you really want to strive to get quality sleep most nights of your life. Which means that even if you're somebody who can quote unquote drink an espresso and then fall right asleep, that you avoid caffeine intake in the twelve hours prior to sleep. **[1:22:47] Andrew Huberman:** I realize not everyone will be able to do that. In fact, I sometimes violate that. So I tend to go to sleep around ten p m every night, sometimes eleven, occasionally twelve midnight, but usually around ten p m every night. I confess that my last ingestion of caffeine is not always ten a m or prior to that. So sometimes I will have caffeine up until eleven a m or maybe noon, and very, very rarely I'll have an afternoon coffee or espresso or non calorie containing soda or tea or something of that sort. **[1:23:26] Andrew Huberman:** But I really try to restrict my caffeine intake to the early part of my day that is before noon given that I go to sleep around ten p m each night and I strongly encourage everyone out there to try and limit their afternoon caffeine intake This is something that doctor Matt Walker who is an expert sleep researcher out of University of California Berkeley Psychology and Neuroscience Department there author of the incredible book Why We Sleep he's been on this podcast many other podcasts talking about the importance of sleep he will remind us and I'll remind you now that the quarter life of caffeine is twelve hours I mentioned this earlier, but I'm going to repeat it again. **[1:24:06] Andrew Huberman:** And that means that if you ingest caffeine at noon, 25% of its effects, more or less, okay. I'm using broad stroke here to talk about quarter life. 25% of that is still going to be bioactive at midnight that night, which will disrupt the early phase of your night, the amount of slow wave sleep, which then in turn will disrupt the amount of rapid eye movement sleep, which will disrupt your emotional processing during the following day, and so on and so forth. **[1:24:33] Andrew Huberman:** Okay, none of this is to say that if you have the occasional cup of coffee in the afternoon, that's going to completely demolish your sleep wake cycle forever. But I really encourage people to avoid drinking caffeine in the twelve hours prior to sleep. And if you can't do that within the ten hours prior to sleep, and if you can't do that within the eight hours prior to sleep, so really try and limit your caffeine intake in the eight to twelve hours prior to going to sleep at night. **[1:24:57] Andrew Huberman:** And of course, slow wave sleep, aka deep sleep, is the sleep that's associated with somewhat mundane dreams, which makes it sound like it might not be that important, but it's also the sleep that's associated with growth hormone release, which is important for protein synthesis, repair of all bodily tissues and metabolism, and slow wave sleep is also critically attached to your immune system's ability to clear out bacteria and viruses that might otherwise infect your tissues. Now I'd like to talk about caffeine and its positive effects on performance when used correctly. **[1:25:31] Andrew Huberman:** And here we are referring to both mental performance and physical performance. The exploration of caffeine as a pro-performance tool has been explored since the nineteen thirties, at least at some of the earliest documented literature on this. Although I have to imagine, given that people have been using caffeine for much longer than that, that long ago somebody realized that by ingesting a certain plant that they felt much more alertness and were able to hunt and gather or do any number of different things better, and as a consequence, decide to consume more of that plant. **[1:26:05] Andrew Huberman:** Now, these days we consume a lot of caffeine in the form of coffee and tea, mainly, and some people consume it in the form of caffeine tablets or energy drinks, etc. Across the board, one finds that caffeine intake at a level of one to three milligrams per kilogram of body weight improves reaction time. That is, it reduces the amount of time to take a physical action or to answer a question correctly with a verbal response. It can also improve coordination. **[1:26:36] Andrew Huberman:** It can also improve memory. Although I do want to mention that whereas most studies of the effects of caffeine on improving mental and physical performance involve taking caffeine at one to three milligrams per kilogram of body weight before the mental task or physical task. There is also a pro-performance effect of caffeine on memory if one takes caffeine after learning certain material, or I should say, being exposed to certain material. We'll come back to that in a few minutes. **[1:27:08] Andrew Huberman:** If one examines reaction time, mood, alertness, focus, and memory, or the ability to call up information from memory, or physical dexterity, power output, endurance, and overall feelings of well-being during exercise and exertion, caffeine has been shown in numerous studies in both men and women to improve all of those metrics significantly. So this is all just to say that caffeine is an incredible performance enhancing tool. Now, what's not obvious from the statement that caffeine is a performance enhancing tool across the board and in men and women and in different contexts, is that the way in which caffeine is taken is very important. **[1:27:58] Andrew Huberman:** Because 90% or more of adults consume caffeine, finding controls for studies of caffeine is really challenging. That is, finding people who don't ingest caffeine regularly is a very challenging task for the researcher. And as a consequence, many of the studies of caffeine on human beings involve depriving regular caffeine users of caffeine, and then examining the effects of caffeine given after a period of, say, five to fifteen days of abstinence in a person that is essentially experiencing mild withdrawal symptoms because they haven't had the caffeine that they were used to getting. **[1:28:36] Andrew Huberman:** So this is an important point, and it's a point that likely exacerbates the observed pro-performance effects of caffeine. Now, all of that isn't necessarily a problem, provided you keep it in mind. And it actually points to a way in which, even if you're a regular caffeine user, you can extract more of the benefits of caffeine. The simplest way to do this, for instance, is to look back to what we talked about earlier in terms of the need to have most of your cortisol increase restricted to the hour or hours just after waking in terms of mood and alertness and performance. **[1:29:12] Andrew Huberman:** One of the ways to increase the peak of that cortisol early in the day is to consume caffeine shortly after that peak occurs. And this was really nicely demonstrated in a study entitled Caffeine Stimulation of Cortisol Secretion Across the Waking Hours in relation to Caffeine Intake Levels. We will provide a link to this study. It's a somewhat complicated study because they looked at a bunch of different times of day for caffeine intake. And I should mention this study, they used this 300 milligrams per day or 600 milligrams per day. **[1:29:44] Andrew Huberman:** So that's quite high, although for people of sufficient body weight and who are accustomed to taking caffeine, it's certainly not going to be in excess of what a lot of people out there are taking. But basically, what they observed was the following. Cortisol responses to caffeine are reduced, but not eliminated in people who consume caffeine on a daily basis. What this means is that if you wake up and as I recommended earlier you avoid drinking caffeine for the first ninety to 120 minutes after waking but you do get some sunlight or other bright light in your eyes in that time maybe even get some exercise in that time which would be even better and then you ingest caffeine **[1:30:21] Andrew Huberman:** you will get a further increase in cortisol which provided it's restricted to the early part of the day is a good thing overall for mood and alertness So this is a simple performance enhancing tool which is to stack caffeine on the tail of that early cortisol peak I should also mention however that in this study they had people do a five day caffeine abstinence prior to being tested with 300 milligrams or 600 milligrams of caffeine So the simple tool to extract from this and other studies like it is that if you want to experience the maximum alertness promoting effects of caffeine when you ingest it early in the day you would abstain from caffeine for five days and **[1:31:02] Andrew Huberman:** then ingest caffeine ninety to 120 minutes after waking I would still hope that you were doing all the other things that I described morning sunlight exercise etc correctly But regardless, it's very clear that a five day abstinence from caffeine, however painful that might be, will increase the performance enhancing effects of caffeine when you take caffeine on that sixth day. Now, I'm sure many of you out there are saying, why would I ever want to abstain from caffeine for five days in order to just get this six day performance enhancing effect? **[1:31:30] Andrew Huberman:** Well, there are a couple of reasons for doing that. Perhaps you're planning to travel to a new time zone and you want to use caffeine as a stimulant to stay up during the day in the new time zone. That's a somewhat unusual case. Others of you might be interested in the pro physical performance effects of caffeine. We'll talk more about these in a little bit. But you want to get the maximum strength increase or the maximum endurance increase from ingesting, in this case, 300 to 600 milligrams of caffeine. **[1:31:58] Andrew Huberman:** Well, in that case, abstaining from caffeine for five days will greatly exacerbate the pro performance effects of caffeine when you take it on that sixth day. Although, admittedly, those five days are likely to be pretty painful if you're a regular caffeine user. Another variation on this, however, might be to have the amount of caffeine that you ingest on a daily basis and then go back to your regular level of caffeine intake on that day in which you need the caffeine to really boost your mood, energy, and performance. **[1:32:25] Andrew Huberman:** Another reason why you might want to abstain from caffeine or reduce your caffeine intake for a period of time and then go back to your regular caffeine intake is simply to identify how much of an effect caffeine is really having on your overall level of daily functioning and mood. This was something that was actually covered in beautiful detail in a book by Michael Pollan, all about caffeine. It's available on Audible. I really enjoyed that book. It describes his experience with the decision to completely abstain from caffeine for a period of months. **[1:32:56] Andrew Huberman:** Although I confess that after hearing that book what it basically made me want to do is never quit drinking caffeine because it sounded as if at least my interpretation was that even after several weeks or months of abstaining from caffeine that he still fantasized about the effects of caffeine but he did mention that when returning to ingesting caffeine after a period of long abstinence that it had almost a uh let's not call it a psychedelic property but it had such obvious effects on mood and alertness and feelings of well-being that it really highlighted for him the extent to which caffeine normally was allowing him to just function what he thought was normally so in other words many of us don't **[1:33:36] Andrew Huberman:** even really know what our normal basal level of cognitive and physical functioning is because we're ingesting caffeine on such a regular basis I confess that as much as I enjoyed that book and as intriguing as his description of caffeine abstinence and then the return to caffeine was I don't intend to ever find out personally Now a very good reason why you might want to abstain from caffeine for a deliberate period of time and then return to caffeine intake is for its physical performance enhancing effects And here we can look to a really interesting study title of which is time course of tolerance to the performance effects of caffeine And what I like about this study is that while yes it **[1:34:15] Andrew Huberman:** does say that abstaining from caffeine and then returning to caffeine intake can enhance physical performance in a very specific way it also says that if you take caffeine regularly you can still see the physical performance enhancing effects of caffeine although they are not quite as robust as they would be had you abstain from caffeine The design of the study is pretty straightforward They had people either ingest three milligrams per kilogram of caffeine for twenty consecutive days Many people are already doing that, I realize, but they had people do that or ensure that they were doing that, or others ingested a placebo for twenty days. **[1:34:51] Andrew Huberman:** So they abstained from caffeine without realizing it. Then, after that twenty days of either ingesting caffeine or a placebo, their peak performance was measured in terms of aerobic output. But prior to that measurement, they had caffeine. Okay, so it's twenty days of caffeine and then a twenty first day of caffeine and then the physical task on that twenty first day, or it's twenty days of abstinence from caffeine, and then on day twenty one, you get caffeine and you get the same physical test. **[1:35:20] Andrew Huberman:** And what they discovered was that the ingestion of caffeine increased peak performance in this aerobic output dramatically if people had abstained from caffeine. But for people that had consumed caffeine all the way through up until that day, it still was effective to ingest caffeine on day twenty one, but not as effective as it would have been had they abstained. And in fact, the magnitude of the what they call ergogenic effect, which is the pro-performance enhancing effect of caffeine, was higher on the first day than in subsequent days when they allowed people to continue caffeine intake. **[1:36:02] Andrew Huberman:** So the takeaway from the study is really straightforward. If you want to get the maximum physical performance enhancing effects of caffeine, you abstain from caffeine for twenty days. Then, on day twenty one, when you're going to do the physical thing, the task, you ingest caffeine about thirty minutes to an hour before you do that physical challenge. Now, twenty days of abstinence is going to be rough for a lot of people. I certainly don't want to sign up for this study. **[1:36:28] Andrew Huberman:** In which case, you might want to do five days of abstinence, as we talked about before, and then on day six is the day that you ingest caffeine and do the physical task. There are even some studies showing that you can abstain from caffeine for just two days, for just forty eight hours. And in particular, if you are a regular user of caffeine, this allows you to, on day three, ingest caffeine at the dose that's appropriate for you and do the physical, or I should mention, mental performance task and perform significantly better than those that have been taking caffeine throughout the entire period leading up to the challenge. **[1:37:03] Andrew Huberman:** So you don't necessarily need to abstain for twenty days in order to get the pro performance effects of caffeine on day twenty one. You could do five days of abstinence prior, or even two days of abstinence prior, or if that's intolerable to you, as it is in my mind to me, to just reduce your caffeine intake slightly, or even perhaps have it if you can tolerate that in the week or two weeks, or maybe even three weeks preceding some physical or mental challenge. **[1:37:29] Andrew Huberman:** Now again this sort of implies that you're going up against a marathon or you're going up against a series of long tests maybe standardized tests in one day there I just really want to point out that there is an abundant literature showing that people perform best on mental tests if they are in the state that they were when they studied for that material now in college I knew a number of people who took this to the extreme thinking that if they were to study under the effects of alcohol that they would be best off consuming alcohol prior to taking exams and it turns out to not be the case Here we're talking in particular about psychostimulant effects of caffeine and **[1:38:07] Andrew Huberman:** other compounds. So, uh, don't think that you can, uh, drink or be under, uh, the influence of THC and then take when you study and then take an exam under the same influence and do just as well as you would had you not ingested anything. Please don't let that be the takeaway. However, do let it be the takeaway that caffeine's effects are made more potent by a brief to not so brief period of abstinence prior to taking a dosage of caffeine. **[1:38:31] Andrew Huberman:** And then the final point to make is that if you are somebody who is not accustomed to drinking caffeine meaning you're hypersensitive to caffeine or you don't regularly ingest caffeine please do not ingest caffeine on the day of any important mental or physical challenge or performance because what you will find is that because you are not caffeine adapted you will experience changes in your thermal regulation in your levels of anxiety and jitteriness and your levels of focus that could be very detrimental to mental or physical performance So you don't want to throw yourself in the deep end by ingesting caffeine if you're not used to it. **[1:39:04] Andrew Huberman:** And I should mention that for people that are not accustomed to ingesting caffeine or are very sensitive to caffeine, even twenty five to fifty milligrams of caffeine, again, the amount that's found in, for instance, a piece of certain types of chocolate can actually cause anxiety. So be careful there. Here I'm referring only to people that are custom with caffeine intake. So what I recommend is to explore the ergogenic effects of caffeine during your training and then to make a decision about what you can reasonably and reliably do in terms of abstinence and then pulse with caffeine on the day of the challenge. **[1:39:37] Andrew Huberman:** I get a lot of questions as to whether or not caffeine has different effects on the nervous system and on performance in particular, depending on phases of the menstrual cycle. So I explored that in my research for this episode, and I found two studies, both of which we will reference in the show note captions. The first one is entitled caffeine consumption and menstrual function, so it's actually the relationship between caffeine and menstrual function. We will do an entire episode about the menstrual cycle and menstrual function. **[1:40:02] Andrew Huberman:** But the other one, as it relates to performance, was published in 2020 in the European Journal of Nutrition, which is ergogenic effects of caffeine on peak aerobic cycling power during the menstrual cycle. And the basic takeaway of this study, this is, frankly, a very nice study, showed that, quote, caffeine increased peak aerobic cycling power in the early follicular, preovulatory, and mid-luteal phases of the menstrual cycle. Thus, the ingestion, and again, here they used three milligrams of caffeine per kilogram of body mass, might be considered an ergogenic aid for women who are in the menstrual cycle during all three phases of their cycle. **[1:40:40] Andrew Huberman:** So keep that in mind, women. For those of you that are regular users of caffeine, or you're using caffeine to enhance physical performance, there does not seem to be any menstrual cycle phase dependent effects of caffeine on performance. That is, caffeine seems to always increase physical performance, regardless of the phase of the menstrual cycle you might happen to be in. I'd like to touch on a little bit more of the use of caffeine for enhancing mental performance. **[1:41:06] Andrew Huberman:** Yes, it is the case that ingesting one to three milligrams of caffeine per kilogram of body weight in the thirty minutes or so prior to doing a memory task or sitting down to doing some studying or learning of any kind, physical or mental performance of any kind is beneficial for all the reasons we talked about before related to dopamine and acetylcholine, etc. But it turns out that it is also the case that spiking one's adrenaline and other so-called catecholamines so this would be dopamine norepinephrine and epinephrine after a bout of learning can greatly enhance memory for the information that one was trying to learn that's right spiking your adrenaline after learning can greatly increase memory for the material you're trying **[1:41:56] Andrew Huberman:** to learn In fact, this is a practice that dates back centuries and was written about in a beautiful annual review of neuroscience on the biology of memory by James McGaw, where he talks about medieval practices of children being taught information and then being thrown literally into cold water to stimulate the release of adrenaline and that increase in adrenaline, while the mechanism wasn't completely understood, it was understood that that sort of shock to the system from the cold water led to better memory and retention of the information that these children had been exposed to. **[1:42:32] Andrew Huberman:** And it turns out the exact same thing is true for adults in the laboratory or kids in the laboratory. And here I'm not suggesting throwing anyone into cold water. If you want to get into cold water, there's a reason we call it deliberate cold exposure on the podcast, is that it should be deliberate and controlled by you, not by somebody else. If it's controlled by somebody else, that might be, uh, you know, military, uh, screening or something. **[1:42:52] Andrew Huberman:** But here we're talking about deliberately increasing your levels of adrenaline and other catecholamines, dopamine, norepinephrine, etc. You can do that certainly by deliberate cold exposure with a cold shower or getting in up to your neck in cold water of any kind. But the other way to do that is to spike your adrenaline by ingesting a one to three milligrams per kilogram of caffeine after sitting down to try and learn some material. I confess that more often than not, I use caffeine the same way that most people use it, which is okay. **[1:43:26] Andrew Huberman:** I'm going to sit down, I'm going to research information for a podcast or assemble some information for a paper or grant, and I want to focus. So I will drink a cup of coffee at the beginning of that, and maybe even throughout that, or a couple of yerba mate at the beginning or throughout that, or I'll sip on one or both throughout trying to learn. And that works quite well in terms of maintaining focus and alertness and retention of information. **[1:43:54] Andrew Huberman:** But it is indeed the case that is the research supports the fact and I've experienced the fact that if I abstain from caffeine while I'm trying to learn something but then I drink caffeine immediately after somewhat surprisingly to me but certainly in a way that's consistent with the research literature memory for the information that I was focused on prior to ingesting that caffeine is much greater and here I'm talking about it as a personal anecdote but this is actually what the data point to both in animals and in humans And if you think about it, it makes perfect sense because the way that the memory systems of the brain are organized is that we go through life experiencing things, we **[1:44:33] Andrew Huberman:** encounter surprises, both good and bad. We go through the motions of things, both typical, mundane, exciting, and novel and not novel. And then every once in a while, something will happen that will spike our catecholamines, dopamine, typically if it's a positive surprise, adrenaline, which can be associated with both positive surprise or positive events and negative events or surprises, and without fail, increases in the catecholamines tend to lock in memories for things that preceded the increase in those catecholamines. **[1:45:10] Andrew Huberman:** Again, the catecholamines being dopamine, epinephrine, and norepinephrine, sometimes all three in combination, sometimes just two of those, sometimes just one of those, depending on the experience. So it makes perfect sense that using caffeine at the end of a learning bout would enhance our memory for the information that we're trying to learn. So if you decide that you want to try and um extract this performance enhancing effect of caffeine, what I recommend would be to try and abstain from caffeine for a day or two prior. **[1:45:39] Andrew Huberman:** But if you can't, to just continue with your normal caffeine intake. But then when you sit down to study or learn something, to not ingest any caffeine as you do that, but then afterward to ingest caffeine. Now, in theory, you could probably further enhance the memory encoding effects of adrenaline and the other catecholamines by drinking caffeine and then taking a cold shower, doing deliberate cold exposure if you really wanted to or had the ability to, or doing some sort of intense form of exercise. **[1:46:08] Andrew Huberman:** And we'll talk in a moment about how caffeine exercise and the adrenaline system interact. But as a brief but relevant aside, brief bouts of intense exercise ranging from ten to fifty minutes or so have been shown to improve memory for information that one was trying to learn prior to the intense exercise. This is work from doctor Wendy Suzuki's lab at NYU, as well as other laboratories. Some of the work that's being done at Stanford in the mind body laboratories, and our laboratory points in the direction of these kinds of effects as well. **[1:46:42] Andrew Huberman:** They all come back to the same general neurochemical theme, which is that when we experience an increase in these catecholamines that include adrenaline, dopamine, and norepinephrine, the memory systems of the brain flip on in a way that try to capture the information and the perceptions and the experiences that we were exposed to just prior to the increase in catecholamines and caffeine, but also exercise, and also cold water. And of course, any of those alone or in combination, all increase the levels of catecholamines. **[1:47:16] Andrew Huberman:** So it makes perfect logical mechanistic sense as to why this would work. And in fact, it does work. If you want to remember specific information, you might consider using caffeine as you move through and absorb and are exposed to that information, but you might also consider using caffeine after being exposed to that information, because studies in animals and humans show that that is a potent way to increase memory for what you were just exposed to. I should mention that what I just described also pushes back on something that I know a number of people perhaps have heard about and maybe even use, which is this notion of the napaccino. **[1:47:51] Andrew Huberman:** I remember hearing about this a few years back. It was a sort of trend, if you will. The trend involved drinking a cup of coffee or double espresso and then going down for a nap, typically in the afternoon, and then waking up. And the idea was that the caffeine would hit your system right at the time that you wake from the nap and that you would be better able to focus and exercise. There are a couple of things about that practice that I don't like. **[1:48:14] Andrew Huberman:** First of all, uh, it implies in most cases that you're napping and ingesting caffeine in the afternoon, which I realize for many students and for people that are comfortable staying up until the wee hours of the night and then waking up late the next day might be compatible with their schedule. But again, because of the sleep diminishing effects of caffeine and we talked about earlier, I'm not crazy about the idea of people ingesting caffeine in the late afternoon in order to, uh, perform better in the late afternoon. **[1:48:45] Andrew Huberman:** Far better would be to restrict caffeine intake to the early part of the day, as we talked about earlier. The other reason is that the data on things like non-sleep deep rest and naps in the afternoon, and again, the the rule here is that you don't have to nap, but if you want to nap, it's been shown that naps of ninety minutes or less or non-sleep deep rest protocols, and you can find those, for instance, there's one with me speaking, you just put NSDR Huberman into YouTube, you can hear that it's completely zero cost. **[1:49:13] Andrew Huberman:** There are other NSDR scripts out there now, of course, that if you prefer those, that those can all lead to increases in one of the catecholamines at least, which is dopamine. That's been shown in, uh, a really nice, uh, neurotransmitter labeling study, not from my laboratory, but from another laboratory, but also can improve mood, focus, and alertness on its own, without the need to ingest caffeine prior to going into those states. And, in fact, ingesting caffeine prior to a nap or ingesting caffeine prior to NSDR is most certainly going to reduce the, uh, effectiveness of that nap and NSDR in restoring natural levels of alertness and focus that would lead to the performance enhancing effect. **[1:49:53] Andrew Huberman:** So I'm not such a fan of the so-called nappuccino, although if any of you out there have derived great benefit from it, um, definitely let me know your protocol, um, and what you've experienced. Put it in the, uh, comment section if you would. Uh, I'd appreciate that. There's another very important and potent use of caffeine for enhancing performance, and this relates not just to the dopamine and epinephrine and the arousal-inducing effects of caffeine, and it doesn't even just relate to the effect of caffeine on enhancing frontal lobe function. **[1:50:25] Andrew Huberman:** It does include all that, but it also includes those reinforcing effects of caffeine that we talked about at the beginning of the episode. And the best way to illustrate these performance-enhancing effects of caffeine that stem directly from its association with reinforcement is to highlight a study, and the title of the study is Blood Dopamine Level Enhanced by Caffeine in Men After Treadmill Running. And as the title suggests, this was carried out in men, but there's no reason to think that the same results wouldn't also be present in women. **[1:50:57] Andrew Huberman:** There are some sex-dependent effects of caffeine, I'll touch on just briefly at the end, but those are largely present in kids, that is, adolescents and teens, as opposed to adults. So this study is really interesting. What they had people do was run on a treadmill and either ingest caffeine again, three milligrams per kilogram of body weight or to not ingest caffeine. And then they looked at levels of dopamine and other neurotransmitters and hormones such as prolactin and cortisol. **[1:51:28] Andrew Huberman:** And the basic takeaway is, as the title suggests, that exercise, while on its own, can increase cortisol in healthy ways, provided it's not too intense and too long. Little note here. If you have trouble recovering from exercise or you want to continue to derive the benefits from exercise, in general, best not to do high-intensity exercise for longer than seventy-five minutes or ninety minutes, probably being the outer threshold. I realize that there are some genetic freaks out there or people that are chemically assisted that can recover from very intense, long bouts of exercise, but most people k- don't do well through long bouts of intense exercise on a regular basis, and limiting their intense exercise to sixty minutes or less, that **[1:52:11] Andrew Huberman:** doesn't include the warm-up, is going to be beneficial. See the episode on, uh, toolkit for fitness if you'd like details on that. Exercise is known to increase levels of dopamine, cortisol, and other catecholamines and neurotransmitters very potently, and things like testosterone and estrogen in ways that we know are beneficial to us, and, of course, have all these positive effects on the musculoskeletal system and cardiovascular effects. But, unbeknownst to most people, ingesting three milligrams per kilogram of caffeine prior to exercise further increases the dopamine release associated with exercise specifically. **[1:52:49] Andrew Huberman:** And this has two important effects. First of all, that increase in dopamine is great because it provides a long-lasting increase in focus, alertness, and motivation not just during the exercise, but also after the exercise. And second, it, that is caffeine and dopamine in combination, act as a reinforcer to make the experience of exercise and the period immediate after exercise more pleasant and, in fact, reinforcing. So, in other words, one way to enjoy exercise more and to enjoy the activities that follow exercise more and to experience a genuine increase in dopamine that's beneficial for mood and alertness is to ingest caffeine prior to exercise. **[1:53:35] Andrew Huberman:** Now, this is important because a number of people out there are exercising, love exercise, love eating great, love doing all the things that are beneficial for their health, but a number of people out there really don't like to exercise. And that serves as a serious block for their willingness and their consistency to exercise. Ingesting caffeine gives us energy to exercise, it increases the release of neurochemicals and hormones that are good for us during exercise, but, as I'm highlighting here, it also increases the reinforcement pathways associated with exercise. **[1:54:15] Andrew Huberman:** That is, it creates a positive feeling about the general theme of engaging in exercise, and it creates a general positive experience of the things that follow exercise. So I think this, if nothing else, is a, uh, call for or support for the idea that ingesting caffeine as a performance enhancing tool makes perfect sense, but for those out there that don't enjoy exercise, in particular certain forms of exercise, ingesting caffeine can change your relationship to that exercise, in other words, make it more positive, much in the same way that ingesting caffeine alongside a certain taste that would otherwise be neutral or maybe even negative can actually make the taste of that particular drink or food positive. **[1:54:59] Andrew Huberman:** So, again, this brings us back to the reinforcing properties of caffeine that are subconscious. It's not just about the enhanced performance in the test or the enhanced performance on the treadmill or with the weights in the gym. It's enhanced feelings of mood and well-being that are genuine because of the effect of caffeine on certain neurotransmitter and hormone systems, but it also is creating an overall milieu of reinforcing all of the things that led into occur during and occur after exercise. **[1:55:29] Andrew Huberman:** I do want to point out something that's very important as it relates to combining things like caffeine and exercise in order to increase dopamine. This is something that came up in the episode that I did on dopamine motivation and drive, which turns out to be one of our most popular episodes. Again, you can find that Huberman Lab dot com and links to all formats with timestamps, et cetera. This also came up in the episode on ADHD because of the relationship between ADHD and dopamine, and that's this notion of dopamine stacking. **[1:55:58] Andrew Huberman:** In the episode on dopamine motivation and drive, I pointed out that while there are a near infinite number of things that can increase dopamine release, most notably positive surprise, um, or positive anticipation or experiencing a win. Um, certainly there are compounds, both drugs of abuse, uh, food, sex, um, and certain supplements that can increase dopamine to varying levels and to varying degrees, both healthy and unhealthy. That's all contained in that episode on dopamine motivation and drive. **[1:56:29] Andrew Huberman:** But what I pointed out is that if you are somebody who tends to experience difficulty with motivation, that so-called dopamine stacking, as I called it, might be something that you want to avoid. What is dopamine stacking? Dopamine stacking would be combining, you know, a highly caffeinated energy drink that also includes the amino acid tyrosine, which is a precursor to dopamine, plus loud music, plus getting yourself really ramped up, then an intense workout. All of that can be great if you do it every once in a while. **[1:56:58] Andrew Huberman:** But what you will quickly find is that the extent to which your dopamine peaks also dictates the extent to which your dopamine will drop after that peak. And when I say drop, I mean drop below baseline. So a lot of people find that if they stack a lot of things to peak their dopamine, that then they experience a low, and it does take some time for them to return to baseline. And I highly recommend not engaging in activities or consuming compounds that are an attempt to accelerate that return to baseline because all it will do is drive that baseline lower and lower. **[1:57:32] Andrew Huberman:** So this requires being able to tolerate a drop in dopamine baseline for a period of time, et cetera. Now the reason I'm bringing this up now in the context of this caffeine episode is I just described a study in which using caffeine prior to exercise increases dopamine after exercise. And so you might be saying especially if you heard that earlier episode wait isn't that dopamine stacking aren't you encouraging me to stack my dopamine well in some sense yes but keep in mind I'm not suggesting that you do this every time you exercise so just as in that earlier episode I emphasized the fact that while stacking multiple stimuli right caffeine or energy drinks and music and et cetera for exercise **[1:58:10] Andrew Huberman:** or for mental work or for any experience for that matter is okay to do every once in a while for most people you don't want to get in the habit of doing it consistently every time you exercise or every time you go out for instance And so you really want to be cautious. That is, you want to protect your both baseline levels of dopamine and your peak levels of dopamine. That said, for people that want to experience an increase in mood, alertness, and performance, or who want to condition themselves, because that's really what it is, it's conditioning yourself by the reinforcing effects of dopamine to increase your liking or maybe even your loving of exercise. **[1:58:47] Andrew Huberman:** Occasionally using caffeine, or frequently using caffeine prior to exercise is fine, but be very careful. And by being very careful, what I mean is pay attention to how you feel in the hours and days after that dopamine increase wears off. So, for instance, if you ingest caffeine and then exercise very intensely and you're feeling great afterwards, but then eight hours later or the next day you're feeling a little bit low, I suggest you don't go back and do the exact same thing right away. **[1:59:16] Andrew Huberman:** I would give you yourself a little bit of time to let that baseline of dopamine return to normal. So again, stacking different things, chemical and behavioral, in order to increase dopamine can be done in a safe way that's beneficial to you, depending on your goals. But be careful about not stacking too many stimuli for dopamine too often. That's the key. Early in the episode, I mentioned one possible caffeine consuming schedule that works very well, that doesn't, fortunately, subject you to, uh, long twenty day bouts or five day or even two day bouts of abstinence, and that's the every other day schedule of caffeine. **[1:59:53] Andrew Huberman:** If you look at the half life of caffeine and you look at its effects on the dopamine system and its performance enhancing effects and how a period of abstinence can in fact increase the performance enhancing effects of caffeine but also take into consideration that caffeine can be habit forming and we can develop a sort of tolerance to caffeine well then what emerges from all of that is that being a person who consumes caffeine every other day can actually help you maximize most of the positive effects of caffeine without subjecting you to the kind of misery that occurs if you're accustomed to consuming caffeine every single day and then suddenly go into a two or five or twenty day abstinence So **[2:00:35] Andrew Huberman:** I myself have never tried an every other day caffeine approach, although I'm considering doing it based on the literature that I've read, and I'm considering doing it in a very specific way, which will be to only consume caffeine on the days in which I resistance train, and since I tend to do that about three or four days per week, organized in a way that's every other day. Again, if you want to see the exercise schedule that I follow, including cardiovascular exercise and weight training, and all the reasons and rationale for what I do and how it maps on to the scientific literature related to health span and lifespan, vitality, et cetera, you can find that Huberman Lab dot com and **[2:01:09] Andrew Huberman:** we had a toolkit for fitness that ought to be posted to our website before long. The every other day schedule of caffeine intake, to me, seems like the most rational one if one wants to maximize on the performance enhancing effects of caffeine without suffering the effects of caffeine withdrawal that are associated with being a regular consumer of caffeine and then stopping caffeine intake, such as headache and irritability and so forth. Not I nor anyone in my line of work wants me to experience those effects, and I'm sure you don't want to experience those effects for you either. **[2:01:40] Andrew Huberman:** So if you're somebody that decides to try the every other day protocol or you are somebody who's already doing that protocol please let me know what your experiences with that are at least by my read of the literature on caffeine and its performance enhancing effects but also the effects of caffeine on neurotransmitter and hormone systems the every other day caffeine schedule does seem to be the most rational and scientifically grounded one in order to maximize on all those effects In addition to so called performance enhancing effects of caffeine there are also the well studied and now fairly well mechanistically understood pro health effects of caffeine Now here when I talk about pro health effects of caffeine I want to be **[2:02:21] Andrew Huberman:** very clear that if your schedule of caffeine intake that is your timing of caffeine intake or anything else for that matter offsets getting regular high quality sleep of sufficient duration well then you are undermining the pro health effects of that thing This is true for exercise, this is true for caffeine, this is true for supplementation, this is true for prescription drugs. Again, you don't want to be neurotically attached to the idea that you have to get perfect sleep every night because that's simply not true. **[2:02:50] Andrew Huberman:** But it is absolutely the case that anything, whether or not it's good for you or bad for you in the short term, that disrupts your sleep because of the timing in which you're doing that thing, is going to undermine your immediate and long term health before long. So, with that said, there are several well described health promoting effects of caffeine ingestion. And once again, when I say caffeine ingestion, I'm referring to that one to three milligrams per kilogram of body weight dosage. **[2:03:20] Andrew Huberman:** There are really nice studies showing that being a regular consumer of caffeine can help offset some of the probability, some of the probability of developing Parkinson's and maybe Alzheimer's related dementia as well. These are not terribly controversial data because of the fact that caffeine is known to increase the release of those catecholamines, dopamine, epinephrine, and norepinephrine, as well as acetylcholine. All those neurotransmitter and neuromodulator systems are the ones that are known to be defective in Parkinson's and Alzheimer's, although there are other transmitter and hormone systems that are defective as well. **[2:03:57] Andrew Huberman:** There are beautiful reviews on the neuroprotective effects of caffeine in neurodegenerative diseases. They're quite extensive, and I'll just refer you to one and the references therein, and we'll provide a link to this in the show note captions. So the title, as the um, uh, topic at hand suggests, is the neuroprotective effects of caffeine in neurodegenerative diseases. This was published in 2016. I'm sure there have been other reviews since then, but it includes many, many quality references and studies both in animals and in humans pointing to the fact that specific enzymes that are associated with the health of, in particular, dopamine neurons, are made more robust by regular ingestion of caffeine. **[2:04:35] Andrew Huberman:** It also points to the fact that the increase in dopamine receptors that is induced by regular ingestion of caffeine that I referred to earlier is another way in which dopamine however many dopamine neurons remain around in people with Parkinson's or people who are aging that lose dopamine neurons naturally that dopamine can have its maximal effect because of the increase in receptors for dopamine that caffeine induces And there are other biological mechanisms that further support why caffeine ought to be neuroprotective including its effects on the acetylcholine system which is one of the major systems disrupted in Alzheimer's dementia So in other words it makes perfect sense as to why caffeine would be neuroprotective Caffeine has also been shown to diminish headache **[2:05:22] Andrew Huberman:** in particular when taken in combination with aspirin and that's because of the effects of caffeine and aspirin on blood flow There's also evidence that caffeine can provide brief but substantial relief from asthma So I wouldn't want people to rely on caffeine as a life uh saving approach to an asthmatic attack. That said, for people that suffer from minor asthma, that caffeine intake, again, of the dosages that we talked about before has been shown to alleviate some of the major symptoms of asthma for anywhere from one to four hours. **[2:05:52] Andrew Huberman:** And I know this is of relevance to a lot of people out there. Because caffeine increases the catecholamines, and in particular because caffeine increases dopamine transmission in the prefrontal cortex, this area of the brain associated with focus and rule setting and context and task switching. Caffeine is known to improve focus and alertness, in particular in people who have symptoms of ADHD or other attention and focus issues. Now, caffeine alone does not appear to be as potent for the treatment of ADHD as are things like Ritalin, Adderall, modafinil, and armodafinil, and Vyvanse. **[2:06:35] Andrew Huberman:** If you would like a sort of head-by-head comparison of prescription drugs, supplements, and things like caffeine, as well as coverage of behavioral tools and nutritional tools, et cetera, that can positively offset some of the symptoms of ADHD, please see the episode that I did on ADHD. Again, that's available at HubermanLab dot com in all formats. But that said, caffeine does increase focus, and it does it through a number of different mechanisms, not the least of which is to increase dopamine transmission in the forebrain, just as a drug like Ritalin or Adderall would, although not to the same extent as a drug like Ritalin or Adderall does. **[2:07:12] Andrew Huberman:** Before we close today, I do want to just briefly return to the reinforcing effects of caffeine that we talked about earlier. This study on the honeybees that showed that bees prefer certain nectars because they contain caffeine, even though they are not aware that those nectars contain caffeine. They just come to like the feeling that those nectars provide them so much that they associate that in a subconscious way with the flowers themselves, and they come to like those flowers. **[2:07:37] Andrew Huberman:** Or human beings, for instance, children that ingest caffeinated beverages come to adore the taste of those beverages. And beautiful studies have been done that describe how children and adults truly cannot distinguish between the taste of a caffeinated and non-caffeinated beverage. And caffeine can be placed into essentially any beverage in order to give us a preference for that beverage or food. In fact, the studies have been done with yogurt. If you put caffeine into yogurt of different flavors, even plain yogurt, which most kids don't like, they will come to prefer whatever flavor contain the caffeine, even if then you remove the caffeine from that flavor. **[2:08:20] Andrew Huberman:** Now, eventually their preference for that flavor will be extinguished. But all of this is just to say that so many of the things that we like, whether or not it's coffee or tea or a given flavor of food or a given experience or even exercise, occur because we ingest caffeine in conjunction with those activities. Now these are not tricks that your nervous system plays on you these are real neurochemical reinforcing effects and I think that we would all do well to think about and to leverage these reinforcing effects much in the same way we would do well to think about and hopefully not leverage aversive effects of certain compounds right the simple way to put this is I or anyone **[2:09:01] Andrew Huberman:** could get you to dislike something someone or someplace by making you feel slightly less good lower mood I don't even have to make you feel nauseous but less good after ingesting something or having a certain kind of interaction or being in a certain environment. Very straightforward to do that because of the way that your nervous system is wired for conditioning. However, there's the positive side of all this, which is that it's very straightforward to reinforce the experience of a given food, including its taste, but all the context around it, the container, the texture, the people you consume it with, where you consume it, et cetera. **[2:09:39] Andrew Huberman:** For instance, I wonder why we are not pairing caffeine with broccoli. And that here I'm not suggesting that people actually do that experiment or play that trick on people, but you have to sort of imagine that if caffeine is this incredible reinforcer of all sorts of things, in particular things that we ingest and would want to ingest more of if it's paired with caffeine, well, then you actually can use caffeine as a tool to increase reinforcement of different things, and you can avoid caffeine as a way to further reinforce things that you would like to stop. **[2:10:15] Andrew Huberman:** And here I'd like to just give the example of sugar cravings. A lot of people ask me how do I avoid sugar cravings I've talked about the use of L glutamine for that I've talked about making sure you're getting enough essential fatty acids and essential amino acids as a way to reduce sugar cravings Please note however that if you are somebody who likes to have your sugar whether or not it's a piece of chocolate or your dessert et cetera I'm not saying that's bad but if you're trying to reduce your sugar cravings ask yourself are you ingesting sugar along with caffeine Could be the caffeine contained in that sugar containing food, like chocolate, or it could be that you're having **[2:10:50] Andrew Huberman:** a cup of coffee along with your pastry, and then you're struggling with sugar cravings. Well, think about it. You're not just being reinforced by the sugar and the effects of sugar on dopamine, which are real and both conscious and subconscious, through the gut to the brain dopamine system and direct on the brain dopamine system. But by co ingesting caffeine, you are also further enhancing the reinforcing effects of sugar. The flip side to all of this is that you could use caffeine as a way to increase your appetite for certain things. **[2:11:18] Andrew Huberman:** I actually know somebody, I won't reveal who this person is, but they are quite a prominent podcaster who ingests 125 to 150 milligrams of caffeine in tablet form, in tablet form, along with herbal tea, and use this as a way to develop a preference for herbal tea because they found that coffee was giving them other effects that weren't good for them. So it works quite well in animals, and it works quite well in insects, and it works quite well in humans. **[2:11:46] Andrew Huberman:** I suppose animals, insects, and humans are all animals at the end of the day. So no surprise there. But it all underscores the extent to which caffeine is an absolutely fascinating molecule. I mean, it's a ability to offset the sleepiness system, if you will, this adenosine system, and to control our schedules in that way, to essentially take a withdrawal against the bank that is adenosine and then pay that back later in the form of getting sleepy later as opposed to when we want to be alert. **[2:12:12] Andrew Huberman:** Its ability to enhance focus, alertness, and mood, and if taken after trying to learn something and remember it, to enhance memory, especially, and its ability to increase VO two max, increase strength. We didn't even talk today about it, but I'll just briefly mention that caffeine ingested in the sorts of doses we talked about earlier, because its effects on the neuromuscular system and the calcium system associated with neuromuscular exertion and fatigue, can increase peak power output and muscle contractability. **[2:12:43] Andrew Huberman:** So it's enhancing performance there as well. And of course, caffeine does a number of other things, just generally related to our overall and basal level of mood and alertness, not the least of which are these increases in dopamine. So caffeine is really an incredible molecule. It's affecting all these various neurotransmitter systems, but not haphazardly. It's increasing dopamine and acetylcholine in the forebrain to increase attention. It's reducing fatigue, it's improving mental and physical performance for some obvious and some not so obvious reasons. **[2:13:12] Andrew Huberman:** And what I think is among the more miraculous and powerful effects of caffeine, it is a potent, potent, potent reinforcer of things, foods, people, and experiences. And it's one that you can leverage in any direction that you like once you understand the way that caffeine exerts those reinforcing properties. So today I've really tried to cover as much as I could about the mechanisms of caffeine action in the brain and body, as well as tools and schedules and dosages in which you can leverage caffeine in order to meet your physical performance, mental performance, and frankly, mental health and overall health goals. **[2:13:50] Andrew Huberman:** If you're learning from and or enjoying this podcast, please subscribe to our YouTube channel. That's a terrific zero cost way to support us. In addition, please subscribe to the podcast on both Spotify and Apple. And on both Spotify and Apple, you can leave us up to a five star review. If you have questions for us or comments about the podcast or guests that you'd like me to interview on the Huberman Lab podcast, please put those in the comment section on YouTube. **[2:14:11] Andrew Huberman:** We do read all the comments. In addition, please check out the sponsors mentioned at the beginning and throughout today's episode. That's the best way to support this podcast. If you're not already following Huberman Lab on social media, we are Huberman Lab on all platforms. So that's Instagram, Twitter, LinkedIn, and Facebook. And all of those places I describe science and science related tools, some of which overlap with the contents of the Huberman Lab podcast, but much of which is distinct from content on the Huberman Lab podcast. **[2:14:38] Andrew Huberman:** So again, it's Huberman Lab on all social media platforms. During today's episode and on many previous episodes of the Huberman Lab podcast, we discussed supplements. While supplements aren't necessary for everybody, many people derive tremendous benefit from them for things like sleep, hormone augmentation, and focus. If you'd like to see the supplements discussed on various episodes of the Huberman Lab podcast, please go to livemomentus dot com slash Huberman. We partner with Momentous because they are of extremely high quality, they ship internationally, and they formulated supplements in the precise ways that are discussed as optimal to take for various outcomes here on the Huberman Lab podcast. **[2:15:15] Andrew Huberman:** If you haven't already subscribed to the Huberman Lab podcast newsletter, it is a monthly newsletter that includes summaries of podcast episodes as well as toolkits, all of which are completely zero cost. All you have to do is provide your email to sign up. We do not share your email with anybody. You do this by going to Huberman Lab dot com, go to the menu and tab down to newsletter, provide your email, you'll get a confirmation link. **[2:15:38] Andrew Huberman:** Click on that link and you'll receive our monthly newsletters, and you can also access any of the previous newsletters that we've released, including the toolkit for sleep, for fitness, deliberate cold exposure, and so on, by going to Huberman Lab dot com, going to the menu, going to newsletter, and there you'll see those as immediately downloadable PDFs. Thank you for joining me for today's discussion about caffeine, both its mechanisms and its many powerful uses. And last but certainly not least, thank you for your interest in science.