Essentials: Master Your Sleep & Be More Alert When Awake

ANDREW HUBERMAN: Welcome to Huberman Lab Essentials, where we revisit past episodes for the most potent and actionable science-based tools for mental health, physical health, and performance. [MUSIC PLAYING] I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. Today's podcast episode is all about sleep.

We're also going to talk about the mirror image of sleep, which is wakefulness. Now, these two phases of our life, sleep and wakefulness, govern everything about our mental and physical health. And we're not just going to talk about what's useful about sleep; we're also going to talk about how to get better at sleeping, and that will include how to get better at falling asleep, timing your sleep, and accessing better sleep quality.

In doing so, we're also going to discuss how to get more focused and alert in wakefulness. So, if you're like most people, which includes me, you have some challenges with sleep at least every third or fifth night or so, and maybe even more often. So, we're really going to go tool-heavy today and talk about tools that can help you fall asleep, sleep better, and emerge from sleep feeling more rested.

So, what determines how well we sleep and the quality of our wakeful state? It turns out that's governed by two forces. The first force is a chemical force; it's called adenosine.

Adenosine is a molecule in our nervous system and body that builds up the longer we are awake. So, if you've just slept for eight, nine, or ten really deep restful hours, adenosine is going to be very low in your brain and body. If, however, you've been awake for 10, 15, or more hours, adenosine levels are going to be much higher.

Adenosine creates a sort of sleep drive or a sleep hunger. A good way to remember this and think about adenosine is to think about caffeine. Caffeine, for most people, wakes them up; it makes them feel more alert.

Caffeine acts as an adenosine antagonist. What that means is that when you ingest caffeine, whether or not it's coffee, soda, tea, or in any other form, it binds to the adenosine receptor. It sort of parks there just like a car would park in a given parking slot.

And therefore, adenosine can't park in that slot. Now, when caffeine parks in the adenosine receptor slot, nothing really happens downstream of that receptor. The receptor can't engage the normal cellular functions of making that cell—and you feel sleepy.

So, the reason caffeine wakes you up is that it blocks the sleepiness receptor; it blocks the sleepy signal. This is why when that caffeine wears off, adenosine will bind to that receptor sometimes with even greater what we call affinity. And you feel the crash; you feel especially tired.

Caffeine has a lot of health benefits. It also, for some people, can be problematic for health; it can raise blood pressure, etc. Caffeine increases this molecule that's a neuromodulator that we call dopamine.

We discussed this in episode one, which tends to make us feel good, motivated, and gives us energy because, as you may have learned in episode one, dopamine is related to another neuromodulator called epinephrine, which gives us energy. In fact, epinephrine is made from dopamine. So, let's just take a step back and think about what we're talking about when we're talking about sleepiness.

If you've ever pulled an all-nighter, you'll notice something interesting. As morning rolls around, you'll suddenly feel an increase in your energy and alertness again, even though adenosine has been building up for the entire night. Now, why is that?

The reason that is because there's a second force that is governing when you sleep and when you're awake. And that force is a so-called circadian force. Circadian means about a day or about 24 hours.

Inside all of us is a clock that exists in your brain, my brain, and the brain of every animal that we're aware of that determines when we want to be sleepy and when we want to be awake. That block of sleep and when it falls within each 24-hour cycle is governed by a number of different things. But the most powerful thing that governs when you want to be asleep and when you want to be awake is light.

In particular, it's governed by sunlight. Now, I can't emphasize enough how important and how actionable this relationship is between light and when you want to sleep. It's quite simple on the face of it, and it's quite simple to resolve.

But people tend to make a big mess of this whole circadian literature, frankly. So, let's just break it down from the standpoint of what's going on in your brain and body as you go through one 24-hour day. Let's start with waking.

Regardless of how well you slept at night or whether or not you were up all night, most people tend to wake up sometime around when the sun rises. When you wake up in the morning, you wake up because a particular hormone called cortisol is released from your adrenal glands. Your adrenal glands sit right above your kidneys, and there's a little pulse of cortisol.

There's also a pulse of epinephrine, which is adrenaline, from your adrenals and also in your brain. And you feel awake. Now, that pulse of cortisol, adrenaline, and epinephrine might come from your alarm clock; it might come from you naturally waking up.

But it tends to alert your whole system and your body that it's time to increase your heart rate, it's time to start tensing your muscles, and it's time to start moving about. It's very important that that cortisol pulse comes early in the day, or at least early in your period of wakefulness. When you wake up in the morning and you experience that rise in cortisol, there's a timer that starts going, and these are cellular timers.

They're dictated by the relation between different organs in your body that say to your brain and body that in about 12 to 14 hours a different hormone—this hormone we're calling melatonin—will be released from your pineal gland. So, there's two mechanisms here: a wakefulness signal and a sleepiness signal. And the wakefulness signal triggers the onset of the timer for the sleepiness signal.

OK, so the rhythm of cortisol and melatonin is what we call endogenous. It's happening in us all the time without any external input. In fact, if we were in complete darkness, living in a cave with no artificial lights whatsoever, these.

. . Rhythms of cortisol and melatonin would continue.

So, if you were in complete darkness, it would happen once per 24-hour cycle, but it would be somewhat later and later each day. Whereas under normal circumstances, what happens is you wake up. And what happens when you wake up?

You open your eyes. When you open your eyes, light comes into your eyes. Now, the way this system works is that you have a particular set of neurons in your eye.

They're called retinal ganglion cells. When light comes into the eye, there's a particular group of retinal ganglion cells, or type of retinal ganglion cells, that perceives a particular type of light and communicates that to this clock that resides right above the roof of your mouth, called the suprachiasmatic nucleus. And the suprachiasmatic nucleus has connections with essentially every cell and organ of your body.

Now, it's vitally important that we get light communicated to this central clock in order to time the cortisol and melatonin properly. When I say properly, I can say that with confidence because we know, based on a lot of evidence, that if you don't get your cortisol and melatonin rhythms right, there are tremendously broad and bad effects on cardiovascular health, metabolic effects, learning, depression, and dementia. So, let's think about what happens when we do this correctly and how to do it correctly.

When we wake up, our eyes open. Now, if we're in a dark room, there isn't enough light to trigger the correct timing of this cortisol-melatonin thing. These rhythms—you might say, well, why won't any light do it?

Well, it turns out that these neurons in our eye that set the circadian clock and then allow our circadian clock to set all the clocks of all the cells, organs, and tissues of our body respond best to a particular quality of light and an amount of light. And those are the qualities of light and the amount of light that come from sunlight. So, these neurons, what they're really looking for, although they don't have a mind of their own, is the sun at what we call low solar angle.

The eye and the nervous system don't know anything about sunrises or sunsets; it only knows the quality of light that comes in when the sun is low in the sky. This system evolved so that when the sun is low in the sky, there's a particular contrast between yellows and blues that triggers the activation of these cells. However, if you wake up a few hours after the sunrise, which I tend to most days personally, you still want to get outside and view sunlight.

You don't need the sunlight beaming directly into your eyes; there's a lot of photons—light energy—that are scattered from sunlight at this time. But the key is to get that light energy from sunlight ideally into your eyes. It's critically important that you get outside to get this light.

I had a discussion with a colleague of mine, Dr Jamie Zeitzer, who's in the Department of Psychiatry and Behavioral Sciences at Stanford—a world expert in this. And he tells me that it's 50 times less effective to view this sunlight through a window, through a car windshield, or through a side window of a car than it is to just get outside with no sunglasses and view light early in the day. Once the sun is overhead, the quality of light shifts so that you miss this opportunity to time the cortisol pulse, and that turns out to be a bad thing to do.

You really want to time that cortisol pulse properly. Because we'll get into this a little bit more later, but a late-shifted cortisol pulse—in particular, a 9:00 PM or 8:00 PM increase in cortisol—is one of the consequences and maybe one of the causes of a lot of anxiety disorders and depression. So, it's kind of a chicken-and-egg thing; we don't know whether or not it's correlated with, it's the cause, or the effect, but it's a signature of depression and anxiety disorder.

Bringing that cortisol pulse earlier in your wakeful period, earlier in your day, has positive benefits, ranging from blood pressure to mental health, etc. I'm not going to list them all off because there are just so many of them. But many, many positive things happen when you are getting the cortisol early in the day, far away from your melatonin pulse.

So, how long should you be outside? Well, this is going to vary tremendously, because some people live in environments where it's very bright. So, let's say it's Colorado in the middle of winter; there's a snowfield, there's no cloud cover.

And you walk outside—there's going to be so much photon light energy arriving on your retina that it probably only takes 30 to 60 seconds to trigger the central clock and set your cortisol and melatonin rhythms properly and get everything lined up nicely. Whereas if you're in Scandinavia in the depths of winter and you wake up at 5:00 AM and the sun is just barely creeping across the horizon and then goes back down again a few hours later, you probably are not getting enough sunlight in order to set these rhythms. So, many people find that they need to use sunlight simulators in the form of particular lights that were designed to simulate sunlight.

You could say, well, the lights in my house or my phone are really, really bright. Everyone's telling us to stay off our phones at night because they're really bright. But guess what?

It turns out that early in the day, your retina is not very sensitive, which means you need a lot of photons, ideally coming from sunlight, to set these clock mechanisms. So, looking at your phone or artificial lights is fine if you wake up before sunrise, but it's not going to work to set these clock mechanisms. So, you want to use sunlight.

If you can't see sunlight because of your environment, then you are going to have to opt for artificial light. And in that case, you're going to want an artificial light that either simulates sunlight or has a lot of blue light. Now, without going off course here, you might be saying, wait, I've heard blue light is bad for me.

Actually, blue light is great for this mechanism during the day. A lot of people will say I should be wearing blue blockers throughout the day. No, that's the exact wrong thing; that should be reserved for late in the evening because light suppresses melatonin.

Sunlight inhibits the pineal; it prevents it from releasing melatonin. Darkness allows the pineal to release melatonin. So the pineal is not the gland or the organ of sunlight; it is the gland of darkness.

In fact, melatonin can be thought of as a sleepiness signal that's correlated with darkness. So, get up each morning and try to get outside. I know that can be challenging for people, but anywhere from two to ten minutes of sunlight exposure is going to work well for most people.

If you can't do it every day or you sleep through this period of the early day low solar angle, don't worry about it. The systems in the body—these hormone systems and neurotransmitter systems that make you awake at certain periods of the day and sleepy at other times—are operating by averaging when you view the brightest light. Some of you, many of you, might be asking, "What else can help set this rhythm?

" Well, it turns out that light is what we call the primary zeitgeber, the time giver. But other things can help establish this rhythm of cortisol, followed by melatonin 12 to 16 hours later as well. The other things besides light are the timing of food intake, the timing of exercise, as well as various drugs or chemicals that one might ingest—not illegal drugs, although those will impact circadian mechanisms as well.

The other thing is sunset when the sun is also at a low solar angle, close to the horizon. By viewing sunlight at that time of day—in the evening or afternoon, depending on what time of year it is and where you are in the world—these melanopsin cells, these neurons in your eye, signal the central circadian clock that it's the end of the day. There was a really nice study that showed that viewing sunlight around the time of sunset—doesn't have to be just crossing the horizon, but circa sunset, within an hour or so—prevents some of the bad effects of light in preventing melatonin release later that same night.

So, let me repeat this: viewing light early in the day is key. Viewing light later in the day, when the sun is setting or around that time, can help protect these mechanisms—your brain and body—against the negative effects of light later in the day. So, let me talk about how you would do that.

You'd go view the sunset, or you would go outside in the late afternoon or evening. Again, if you want to do this through a window at work, that's fine, but it'll take 50 times longer. So, the best thing to do is just to get outside for a few minutes—anywhere from two to ten minutes—in the afternoon as well.

Having those two signals arriving at your central clock lets your body, your internal world, know when it's morning and knows when it's evening. This is tremendously powerful. There's always a lot of questions about how long?

How much? How do I know if I've had enough? You'll know because your rhythm will start to fall into some degree of normalcy.

You'll start to wake up at more or less the same time each day, and you'll fall asleep more easily at night. Generally, it takes about two or three days for these systems to align. So, if you've not been doing these behaviors, it's going to take a few days.

But they can have tremendous benefits—and sometimes rather quickly—on a number of different mental and physical aspects of your health. Now, let's talk about the bad effects of light. Because light is not supposed to arrive in our system at any time, and nowadays, because of screens and artificial light, we have access to light at times of day and night that normally we wouldn't.

Now, earlier I said that you need a lot of light—in particular sunlight—to set these clock mechanisms. That's true. But there's a kind of diabolical feature to the way all this works, which is that the longer you've been awake, the more sensitive your retina and these cells are to light.

So that if you've been awake for 10, 12, or 14 hours, it becomes very easy for even a small amount of light coming from a screen or from an overhead light to trigger the activation of the clock and make you feel like you want to stay up later, making it harder to fall asleep and disrupting your sleep pattern. Okay, so the simple way to think about this is: want as much light as safely possible early in the day—morning and throughout the day, including blue light—and you want as little light coming into your eyes, artificial or sunlight, after, say, 8:00 PM. And certainly, you do not want to get bright light exposure to your eyes between 11 PM and 4 AM.

And here's why: light that arrives to the eyes between 11:00 PM and 4:00 AM approximately suppresses the release of dopamine. This neuromodulator that makes us feel good is sort of an endogenous antidepressant, and it can inhibit learning and create all sorts of other detrimental effects. It does this through a mechanism—for those of you who want to know—the neural pathways that involve light to the eyes.

That's then signaled to a structure called the habenula. When that habenula gets activated, it's actually called the disappointment nucleus because it makes us feel less happy and more disappointed, potentially leading to certain forms of depression in the wakeful state. Now, if you wake up in the middle of the night and you need to use the bathroom or you're on an all-night flight and you need to read or whatever it is, fine.

Every once in a while, it's not going to be a problem to get bright light exposure to your eyes in the middle of the night. But if you think about our lifestyle nowadays—being up late looking at phones—even if you dim that screen, you're triggering this activation because your retinal sensitivity and the sensitivity of these neurons has gone up late in the day. For those of you who are experiencing challenges with mood, those of you who have anxiety, learning problems, or issues focusing, the questions I usually get are, "How can I focus better?

" One of the best ways you can support your mechanisms for good mood, mental health, learning, focus, metabolism, etc. , is to take control of this light exposure behavior at night and not get much or any bright light exposure in the middle of the night. These cells in our eye.

. . Neurons that signal the central clock reside mostly—not exclusively, but mostly—in the bottom half of our retina.

And because we have a lens in front of our retina and because of the optics of lenses, that means that these cells are actually viewing our upper visual field. This is probably not coincidental; these cells were essentially designed to detect sunlight, which is overhead, of course. So, if you want to avoid improper activation of these neurons, it's better to place lights that you use in the evening low in your physical environment—such as on desktops or even the floor, if you want to go that way—as opposed to overhead lights.

Overhead fluorescent lights would be the worst; that would be the worst-case scenario. Lights that are overhead and have a little bit softer yellow or reddish tints would be slightly better. But dim lights set low in the room are going to be best because they aren't going to activate these neurons and therefore shift your circadian clock.

But let's talk about what light can do in terms of shifting us in healthy ways. The way to think about this whole system, again, is that you've got adenosine building up depending on how long you've been awake, and it's making you sleepy. And then you have their circadian mechanisms that are timing your wakefulness and timing when you want to be asleep, mainly through cortisol and melatonin.

But there are a bunch of other things that are downstream of cortisol and melatonin, like we tend to be hungrier during our wakeful period than late at night. Some people like to eat late at night. But if you're finding that you can't become a day person or a morning person, shifting your light exposure, exercise, and food intake to the daytime will help.

Jamie Zeitzer and colleagues did a beautiful study showing that if you turn on the lights before waking up—so around 45 minutes to an hour before waking up—even if your eyelids are closed, provided you're not under the covers, after doing that for a few days, it increases your total sleep time and shifts forward the time at which you feel sleepy. It makes you want to go to bed earlier each night. Now, in a kind of diabolical way, they did this with teenagers who are notorious for wanting to wake up late and stay up late.

What they found was that bright light flashes—just turning on the lights in their environment, overhead lights, because they're trying to activate the system—activated the neurons even through the eyelids before these kids woke up. This made those kids naturally want to go to bed earlier, and they ended up sleeping longer. So that's something you could try: you could put your lights on a timer to go on early in the day before you wake up.

You could open your blinds so that sunlight is coming through. And again, if you curl up under the covers, then it's not going to reach these neurons. But it's remarkable; light can actually penetrate the eyelids, activate these neurons, and reach the central clock.

That study illustrates a really important principle of how you're built, which is your capacity for what are called phase advances and phase delays. I don't want to complicate this too much, so the simplest way to think about phase advances and phase delays is that if you see light late in the day, and in particular in the middle of the night, your brain and body—for reasons that you now understand—will think that that's morning light, even though it's not sunlight, because you have this heightened sensitivity, and it will phase delay; it will delay your clock. It will essentially make you want to get up later and go to sleep later.

So the simple way to think about this is: if you're having trouble waking up early and feeling alert early in the day, you're going to want to try to get bright light exposure even before waking up because it will advance your clock. It's sort of like turning the clock forward. Whereas if you are having trouble waking up early, you definitely don't want to get too much light exposure, or any light exposure to your eyes late in the evening and in the middle of the night, because it's just going to delay your clock more and more.

What you're trying to do is provide anchors. You're trying to provide consistent, powerful anchors so that your cortisol, your melatonin, and then everything that cascades down from that—like your metabolism and your ability to learn, your sense of alertness, your dopamine, your serotonin—all of that is timed regularly. One of the reasons why there's so much challenge out there with focus, anxiety, and depression—there are a lot of reasons for that—but one of the reasons is that people's internal mechanisms aren't anchored to anything regular.

These systems, again, will average, but if you can provide them consistent light anchors early in the day and in the evening while avoiding light at night, you will be amazed at the tremendous number of positive effects that can come from that at the level of metabolic factors, hormones, and just general feelings of well-being. This is why whenever people ask me, "What should I take? "—which is one of the most common questions I get—"What supplements should I take?

What drugs should I be taking? What things should I be taking? "—the first question I always ask them is, "How is your sleep?

" And 90% of the time, they tell me they either have trouble falling asleep, or staying asleep, or they don't feel rested throughout the day. A brief note about naps: naps, provided that they're less than one ultradian cycle—provided they're 20 minutes, 30 minutes, or even an hour—can be very beneficial for many people. You don't have to take them, but many people naturally feel a dip in energy and focus late in the afternoon.

In fact, if we were to look at wakefulness, what we would find is that you get that morning light exposure; hopefully, your cortisol goes up, people start feeling awake, and then around 2, 3, or 4 in the afternoon, there's a spike in everything from alertness to the ability to learn. Some metabolic factors drop, and then it just naturally comes back up, tapering off as the night progresses. So, for some of you, naps are great.

I love taking naps. Some people wake up from naps feeling really groggy. That's probably because they're not sleeping as well as they should at night or as long as they should at night.

And so they're dropping into REM sleep or deeper forms of sleep during the daytime. Then they wake up and feel kind of disoriented. Other people feel great after a nap.

That's another case where, just like with caffeine, you sort of have to evaluate for yourself. OK, so naps are going to be good for some people, not for others. I personally like to take a nap around 3 or 4 PM, but there's a practice that I've adopted in the last five years that I've found to be immensely beneficial.

That is sort of like napping but isn't napping. It's a thing that they call yoga nidra. Yoga nidra actually means yoga sleep, and it's a sort of meditation that you listen to.

Meditation and yoga nidra scripts have been immensely helpful for me in terms of accelerating the transition to sleep. They involve taking a few minutes, 10 to 30 minutes or so, just like you would for a nap, and listening to a script almost passively. It involves some particular patterns of breathing and some other kinds of body scan techniques that can really help people learn to relax—not just in that moment, but get better at relaxing and turning off their thoughts in order to fall asleep when they want to do that at night.

In other words, they're always good for you because it's a training mechanism by which you self-train your nervous system to go from a state of heightened alertness that you don't want to a state of relaxation that you do want. It's really teaching you to hit the brakes. And that brings us to an even more important point, perhaps: we've all experienced that we can stay up if we want to.

If we want to stay up late on New Year's or we want to pull an all-nighter, some people can do that more easily than others, but we're all capable of doing that. However, it's very hard to make ourselves fall asleep. There's a sort of asymmetry in the way our autonomic nervous system governs this alertness-calmness balance, particularly with the sympathetic and parasympathetic nervous systems.

There's an asymmetry where we can more easily engage wakefulness and drive wakefulness. We can force ourselves to stay awake more readily than we can force ourselves to fall asleep. One of the things that I say repeatedly and will continue to say is that it's very hard to control the mind with the mind.

When you have trouble falling asleep, you need to look to some mechanism that involves the body. All the things I've described—meditation, hypnosis, yoga nidra—include emphasized exhalation, different ways of lying down, and controlling the body. We're going to delve into breathing in depth at another time, but all of those involve using the body to control the mind rather than trying to wrestle your mind into a certain pattern of relaxation.

When we're having trouble controlling the mind, I encourage people to look toward the body, to seek sunlight, and to avoid bright light if that happens to be late at night. There's a theme emerging: in order to control something we call the nervous system, we have to look back to some of the things we discussed earlier, like sensation and perception. But we have to ask, what can we control?

Well, I'm talking about controlling light exposure, your breathing, and body awareness—non-sleep deep rest, or what I will refer to hereafter as NSDR—as a way to reset one's ability to be awake after you emerge from NSDR. This can help improve wakefulness and emotional stability, making it better and easier to fall asleep when you want to at night. Now, non-sleep deep rest does have some research to support it.

There's a beautiful study conducted out of a university in Denmark. I will later provide a link to that study, which showed that this meditation—and yoga nidra-type meditation—allows dopamine and other neuromodulators in an area of the brain called the striatum to reset itself. In other words, NSDR can reset our ability to engage in the world in a very deliberate way.

OK, so what about things we can or maybe should or should not take in order to control and access better sleep and better wakefulness? There are a couple of things that align directly with the biology related to falling and staying asleep as well as with the biology of wakefulness. There's a whole category of stimulants—cocaine, amphetamines, and prescription stimulants designed for the treatment of narcolepsy.

Things like modafinil or armodafinil are designed to create wakefulness; they are all essentially chemical variants of substances that increase epinephrine and dopamine. Of course, I'm of the standpoint that substances like cocaine and amphetamines are just outright bad. They have so many addictive and harmful effects.

In the proper setting, prescribed by a qualified professional, things like modafinil for narcolepsy might be appropriate. I know that many people take Adderall even though they haven't been prescribed it in order to increase wakefulness. That is essentially illegal, but it's also abusing the system in the sense that you're pushing back on the adenosine system, slightly differently than you do with caffeine.

It will make you feel more alert, but there tends to be a heavy rebound, and they do have addictive potential. There are also other effects of those stimulants that can be quite negative. However, there are some supplements and strategies that are certainly safer, and that, in cases where you're doing all the right behaviors—exercising and eating correctly—but are still having trouble with sleep, can be beneficial for falling and staying asleep.

Now, I want to be very clear: I am not promoting supplements; I'm simply pointing you toward some things that have been shown in peer-reviewed studies to have some benefits. The first one is magnesium. There are many forms of magnesium.

But certain forms of magnesium can have positive effects on sleepiness and the ability to stay asleep, mainly by way of increasing neurotransmitters like GABA. There are a lot of forms of magnesium out there, but one in particular is magnesium threonate (T-H-R-E-O-N-A-T-E), which you have to check to see if this is right for you. Check with your doctor.

The other thing is theanine (T-H-E-A-N-I-N-E). 100 to 200 milligrams of theanine, for me, also helps me turn off my mind and fall asleep. Interestingly, theanine is now being introduced to a lot of energy drinks in order to take away the jitters that are associated with drinking too much caffeine or with some other things that are in the energy drinks.

So just a consideration. Again, I'm not here to tell you what to do or not do, but just want to arm you with information. The thing about theanine and magnesium is that taken together, they can make some people so sleepy and help them sleep so deeply that they actually have trouble waking up in the morning.

So you have to play with these things and titrate them. If you decide to use them, again, I would not start by taking supplements. I would start by getting your light viewing behavior correct, then think about your nutrition, then think about your activity, and finally consider whether or not you want to supplement.

We already talked about melatonin earlier. There's another supplement that can be quite useful, which is apigenin (A-P-I-G-E-N-I-N), a derivative of chamomile. 50 milligrams of apigenin can also augment or support the creation of sleepiness to help you fall asleep and stay asleep.

It is important to note that apigenin is a fairly potent estrogen inhibitor. Therefore, women who want to keep their estrogen levels high or at whatever levels they happen to be at should probably avoid apigenin altogether. Men should take that into consideration as well; men need estrogen too.

You don't want to completely eliminate your estrogen, as that can create all sorts of bad effects on libido, cognition, etc. So, for some people, apigenin is going to be a pretty strong estrogen inhibitor. Thank you so much for your time and attention, and above all, thank you for your interest in science.