AMA #12: Thoughts on Longevity Supplements (Resveratrol, NR, NMN, Etc.) & How to Improve Memory

ANDREW HUBERMAN: Welcome to the Huberman Lab podcast, where we discuss science and science-based tools for everyday life.

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I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. Today is an Ask Me Anything episode, or AMA. This is part of our premium subscriber channel. Our premium subscriber channel was started in order to provide support for the standard Huberman Lab podcast, which comes out every Monday and is available at zero cost to everybody on all standard feeds-- YouTube, Apple, Spotify, and elsewhere.

We also started the premium channel as a way to generate support for exciting research being done at Stanford and elsewhere, research on human beings that leads to important discoveries that assist mental health, physical health, and performance. I'm also pleased to inform you that for every dollar the Huberman Lab premium channel generates for research studies, the Tiny Foundation has agreed to match that amount. So now we are able to double the total amount of funding given to studies of mental health, physical health, and human performance.

So without further ado, let's get to answering your questions. The first question is about resveratrol. The question specifically is, and I quote, "There seems to be a lot of conjecture about resveratrol and whether or not it can extend lifespan. Could you please tell us your thoughts on this subject?"

Okay, well, I will indeed tell you my thoughts on this subject. And I'll use it as an opportunity to also give you my thoughts about supplementation for sake of longevity, that is, for extending lifespan more generally. So resveratrol got a lot of attention some years back because of at the time, it was believed that supplementing with resveratrol could impact certain cellular pathways that would extend not just the lifespan of those individual cells but perhaps the lifespan of the entire organism, meaning us, humans.

And as a consequence, supplements such as resveratrol supplements but also grape seed extracts, which we know contain a fair amount of resveratrol or can be converted into resveratrol, also received a lot of attention for their potential to increase lifespan. I think by now, 2023, it's fair to say that most of that thinking has been, let's just say, debunked.

I think that most people understand that while, indeed, resveratrol might have some positive effects on the functioning of our cells, that there is very little, if any, direct evidence that resveratrol can increase lifespan. If you are aware of any data to the contrary that is modern, is highly controlled, and, even better, was carried out in human studies or nonhuman primate studies or even mouse studies, please put links to those in the comments on YouTube because I'd love to see those studies, especially recent studies.

But my current line of thinking is that resveratrol, while it may have certain health benefits, does not seem to increase lifespan. Now, with that said, that doesn't mean that things like resveratrol or grape seed extract are of zero utility. In fact, I take 400 to 800 milligrams of grape seed extract, usually with a meal-- it's just part of my standard supplementation stack-- every single day. But I do that mainly for its effects on vascular function and blood flow and a few other effects that grape seed extract has been related to.

The data there, I would say, are reasonably strong, strong enough, certainly, that when weighed against the potential downsides of taking grape seed extract, including the cost of grape seed extract, lead me to take 400 to 800 of grape seed extract per day. I just do that as a kind of general insurance policy against a number of things. And it's part of a small kit of supplements that I take that fall into that category, meaning supplements that appear to be very safe, certainly at the dosages that I just referred to, supplements that potentially are having positive effects on our cells, and that are fairly, if not very, low cost.

So that's why I take grape seed extract. I do not take it for its potential impact on resveratrol and resveratrol-related pathways per se and certainly not to extend my lifespan. So that basically answers the question that I was asked, which is, what are your thoughts on resveratrol for extending lifespan? My answer was, I don't think it extends lifespan. But I take something related to resveratrol for other health purposes.

And by the way, I certainly wouldn't place grape seed extract in my list of top five or even top 10 supplements. If somebody, for instance, said, I want to take anywhere from 1 to 10 supplements, and I have x amount of budget to devote to supplementation and I'm thinking about taking grape seed extract, would that be one of the top 10 supplements you would recommend? I certainly wouldn't put it in the top 10.

And by the way, at some point in the not too distant future, I will put online-- so I'll probably do a podcast episode-- listing out all the supplements that I take and the rationale behind those and how long I've taken them and the effects that I've observed both subjectively and in my blood work and what I recommend to other people, what I don't recommend to other people, what's specific to me, and so on and so forth. But meanwhile, that's my answer to the question. I don't think resveratrol increases longevity, at least I'm not aware of any direct evidence for that in humans.

Now, with that said, let's use this as an opportunity to talk about some of the other so-called longevity supplements and drugs that are often discussed online and elsewhere in terms of their efficacy to increase lifespan. About four or five years ago, there was a sudden and increased attention on NAD-related pathways for increasing longevity.

So the NAD pathway, as some of you may already know, is a pathway within all of our cells. This is a pathway that is highly active in young animals and humans. But all animals in humans across the entire lifespan make NAD in their cells. It's related to cellular energetics, that is, the production of energy in cells. It has direct relevance to mitochondrial function and mitochondrial function to it.

And that's a discussion unto itself. But suffice to say that the pathway leading to NAD includes things such as NR and NMN. NR and NMN are considered by many to be precursors to NAD. Okay, so why am I telling you all these acronyms? Here's the deal. The argument was made, in fact, by some prior guests on the Huberman Lab podcast and elsewhere, that by increasing NAD levels in our cells, that one could potentially extend lifespan.

And there are generally three ways in which people have attempted to do that. We'll talk about whether or not increasing NAD in our cells actually increases lifespan in a moment. But for the time being, let's just talk about some of the ways that people have tried to increase NAD within their brain and body.

The most typical ways that people have done that is through, until very recently, supplementation. And so there are supplements out there, such as NR, which we know can increase NAD levels. So this is taken as a pill or a powder, typically as a capsule or a powder. Or by taking NMN, which-- and here, there's been some, let's just say, debate as to whether or not taking NMN actually leads to increases in NAD within our cells, whether or not it can get into our cells, whether or not it's converted into NAD, and so on and so on.

But there, again, the idea was by taking NAD either in capsule form or it's sometimes taken as a sublingual powder, that one could increase NAD levels and thereby potentially increase lifespan. And then there's a third way that's commonly used to try and increase NAD levels, and that's by infusing by intravenous infusion or, in some cases, by oral administration, either liquid or pill form, NAD itself.

Now, I confess that I have tried all three of these approaches. Okay, so I do indeed take an NR supplement every day. I take 500 of NR. I also and have separately taken an NMN supplement. I take sublingual NMN. So I'll take anywhere from one to two grams of NMN as a sublingual powder, which, as the name suggests, you put it under your tongue, and it dissolves there. It's got this kind of tangy flavor.

And the goal for me in taking NR and NMN each day-- and I should mention that sometimes I have just taken NMN or just NR to do the comparison between NR and NMN for me in a subjective way, just comparing what are my energy levels, how do I feel, whether or not there are any side effects. And then I've also taken them together. And I've arrived at a protocol where I take NR and NMN every single day. And the goal of that is, indeed, to increase NAD levels within my system.

However-- and I really want to emphasize this-- I do not take NR and NMN in order to increase my lifespan. In fact, at this point in history, it's unclear and seems somewhat unlikely that increasing NAD is going to increase lifespan. But I think we should always keep our minds open. There may be data to arrive in the future that shows that that actually does happen in humans.

Now, there are some animal data suggesting that increasing NAD, either by taking NR and/or NMN, can increase lifespan. But frankly, that is not why I take NR and NMN. I take NR and NMN in an effort to increase NAD. And now I realize what I'm about to say is entirely subjective, and I really want to highlight that. What I'm about to describe is my experience. It is not based on any peer-reviewed studies.

When I take NR and NMN at the dosages I talked about a little bit earlier, it gives me a lot of sustained mental and physical energy throughout the day. Now, I've always had a lot of mental and physical energy. But I'm 48 years old now, and I'm interested in doing anything that I safely can to keep those levels of energy as high as is reasonable. I don't want to have so much energy that I can't sit still or so much energy that I can't sleep at night.

But I find that when I take NR and NMN in the morning-- so typically I'll do this before my first meal. I don't really regulate how close it is to that first meal. So I'll wake up, use the bathroom, hydrate, get my sunlight, do all the things I've talked about on other podcasts. But I'll take my NR and NMN sometime usually within about an hour or two of waking up and typically at least 30 minutes to two hours before my first meal, which, for me, usually arrives around 11:00 AM. So sometimes I'll take it long before my first meal.

In any event, it gives me a lot of energy. And I seem to have that energy throughout the day. I have gone periods of time where I stopped taking NR and/or NMN. And while I didn't feel as if I was completely depleted of energy, I did notice a decrement in energy compared to when I took NR and NMN.

Now, I want to be very, very clear. I have no, zero, financial relationship to any company that manufactures NR. And while I used to have a relationship to a company that made NMN, as of recently, there's an FDA ruling that has made NMN not available as a supplement in the wider world. So earlier this year, that is, in 2023, there was a filing for NMN as a experimental drug in a clinical trial.

And as a consequence, NMN was listed as a banned or not allowed to be commercially sold supplement. And that has to do with some of the legality around clinical trials. And when something is listed as an experimental drug, it can't be listed as a supplement. Nonetheless, you can still find NMN on the open market. You can find it on Amazon. I can't really speak to the purity of one source versus another. You'll have to explore that on your own.

But I will say this, even though I said it before. I have zero financial relationship to any company that manufactures and sells NMN at this time or NR at this time. So the short summary to this whole discussion about NR and NMN is that I take NR and NMN, but I take it because I like how it makes me feel. It increases my energy levels in the morning and throughout the day, and it does so in a way that tapers off nicely in the evening, and I can still fall asleep, et cetera.

I do not take it with any expectation that it's going to increase my lifespan, simply because I don't think the data substantiating the extension and lifespan are here yet. They may arrive at some point. But I don't think that they are here yet. So there are a good number of people out there that still take NR and/or NMN and are doing so in efforts to increase NAD.

And so let's take a moment and talk about increasing NAD directly because that's something that I have some recent experience with and that's becoming more common and is, yes, still FDA approved, at least as far as I know. There are companies that can come to your house or you can go to a facility, and they will give you an NAD infusion. So they will infuse you directly with NAD into the vein.

I've done this twice now. And I will say, as most people experience when they do an NAD infusion, it's pretty darn uncomfortable, in fact, so much so that a lot of people have to take anti-nausea meds in order to get the NAD infusion. I opted to not take the anti-nausea meds, not because I'm particularly tough but because I don't like taking additional medication if I can.

But I've taken anywhere from 500 to 1,000 milligrams of NAD by infusion. I did that at times when I was feeling particularly run-down or post-illness. And I did, indeed, find that after the NAD infusion was complete, I felt much, much better in a number of different ways-- improved sleep, improved vigor coming off those illnesses. I felt much better. But, again, there is no clinical trial exploring NAD infusion for sake of vigor, et cetera, that I am aware of.

I just happen to be somebody who is interested in exploring these tools and techniques from time to time. And I deemed this as safe. Whether or not safe for you, you have to explore with your physician. Also, I do want to re-emphasize what I said a moment ago. Those NAD infusions are pretty darn uncomfortable. You can have the person administering the infusion adjust the rate of the infusion so that the drip is slower, which makes it more tolerable, as opposed to trying to get the whole infusion bag in there in 45 minutes or less.

I just wanted to get the whole thing over with. So I just said, put it in as quickly as you reasonably and safely can. It took about an hour, maybe 45 minutes to an hour. Initially, I felt nauseous. I felt like someone was stepping on my chest. I felt like someone was stepping on my legs. I felt like-- well, I just felt lousy. I felt so awful. And then after about 10 minutes, it passed, and I felt fine.

And then after the infusion was done, as I mentioned before, I felt terrific. I was still able to fall asleep that night just fine, although I did make it a point to do this earlier in the day. I have heard of some people doing NAD infusions later in the day and having challenges with sleep. But, again, that's just anecdotal, or we could call it anecdata if you want. But it's anecdotal. It's generally assumed, for obvious reasons, that NAD infusions are more effective at increasing cellular levels of NAD than NR or NMN or both together, although the direct comparison has not been made, as far as I know.

And there's still this general question as to whether or not any of this stuff is getting into cells directly and impacting NAD levels in specific cells, although I think most people assume that the NAD infusions certainly are. Now, there are a number of different experts out there who debate all the fine points of everything that I just said, people like Dr. Charles Brenner, and people like Dr. David Sinclair, people like Matt Kaeberlein. There are people who really actively and, let's just say, heatedly debate all the issues that I just talked about.

I think the greatest debate is around whether or not increasing NAD levels in cells actually increases lifespan. But there's also a debate around whether or not NR is more advantageous than NMN, whether or not all of this is too premature to explore yet already. Again, I just want to restate for the third time, I don't do any of this stuff in these NAD pathways for sake of increasing lifespan. I do it for sake of the vitality and energy effects that I subjectively experience.

I must say that the NAD infusions are expensive enough, inconvenient enough, and let's just say uncomfortable enough that I don't see myself doing them very often, although perhaps maybe doing them a couple of times a year or more makes sense, should I find myself feeling run-down or post-illness fatigue or things of that sort. I would be very curious to learn from any of you, the audience, what sorts of things you've experienced when, if perhaps, you've explored NR supplementation, NMN supplementation, or NAD infusions.

And as I mentioned earlier, there's now a growing number of different products that claim that you can take NAD orally, so either in pill, tincture, or other forms, so no requirement for an infusion. But I'm not aware of any studies that have directly linked oral NAD to NAD levels in cells and how those two things relate. So lots more important science to be done in this area, lots more debate surely to be had. And any time we talk about supplements, I just want to emphasize several times that I do see supplements as, indeed, supplements.

I think only by getting your light exposure, sunshine, movement, nutrition, stress modulation, social relationships, et cetera, correct, should you even begin to consider supplementation because supplementation is just not at the foundation of mental health, physical health, and performance. It is, indeed, something that, provided it fits within your safety and economic frameworks, could potentially enhance mental health, physical health, performance in certain ways. But it's certainly not the foundation from which you build mental health, physical health, and performance.

So now we've talked about resveratrol, a little bit about grape seed extract, we talked about NR, NMN, and NAD and the NAD pathway, there are a few other things that are commonly discussed in the longevity sphere, let's call it, things such as metformin. I'll just be very direct and say I do not take metformin. And I also don't take what some people call the poor man's version of metformin, which is berberine.

Berberine gives me brutal headaches. Berberine lowers blood glucose. That's why I think it's giving me brutal headaches. A lot of people have explored or are thinking about exploring taking metformin or berberine for sake of lowering blood glucose and lowering a particular cellular, let's just say, pathway or a set of molecules, mTOR being the most common of them. mTOR-- mammalian Target of Rapamycin-- is abundant in developing cells.

It's responsible for the growth of individual cells. And the amount of mTOR in our cells tapers off across our lifespan. mTOR and its pathways is something that I've actually worked on fairly extensively in my laboratory in the context of the regeneration of the visual system. So I'm very familiar with it. And for sake of convenience and ease in this conversation, we can just think of mTOR as something that's abundant in cells during development and any time cells are growing, including the growth of tumor cells and cellular growth at any stage of the lifespan.

So the logic that people have waged is that drugs like metformin or compounds like berberine that reduce mTOR levels or impact the mTOR pathway in ways that lead to net decreases in mTOR-- the logic is that that could somehow increase lifespan. There's also the logic that fasting can reduce mTOR, which can increase lifespan. I don't think there's any direct evidence for that yet, however, at least not in humans.

So I'll tell you, I don't take berberine for the reasons I mentioned before. It makes me feel uncomfortable. I don't-- not psychologically uncomfortable. It makes me feel physically uncomfortable. I don't take metformin because expert colleagues of mine, including Dr. Peter Attia, have come on this podcast. In fact, we did a collaboration journal club podcast that we'll provide a link to in the show note captions, during which we, meaning mainly Peter, reviewed the data, the peer-reviewed data on metformin and lifespan.

And at least to my understanding, at present, there isn't sufficient data to support taking metformin for increasing lifespan. So that's why I don't take it. I may in the future if more data come out and things change. But right now, I see no reason to take metformin to increase my lifespan. So I don't take metformin.

Similarly, there's a lot of discussion out there about rapamycin. Remember, mTOR-- mammalian Target of Rapamycin-- is so named because it's a target of this drug, which is used largely as an anticancer drug but has other purposes as well. Rapamycin is actively under investigation, which makes it sound like there was a crime committed, but as far as I know, there wasn't. Under active scientific exploration would be the more accurate way to say it-- by excellent researchers such as Dr. Matt Kaeberlein up at the University of Washington in Seattle.

He's been looking at rapamycin for its ability to extend lifespan, focusing on many different species, including dogs. So he has a dog longevity project. So that's really interesting. Dr. Peter Attia has talked a lot about rapamycin and did a recent podcast about rapamycin with not only Matt Kaeberlein but one of the experts in the world on mTOR. So I invite you to check out that podcast if you want to learn about rapamycin.

So there is a fair amount of understanding about the biological pathways of rapamycin and mTOR and so on. And there are clinician physicians like Peter, as well as others, who are quite excited about the potential for rapamycin to extend lifespan, although you have to go directly to Peter to find out exactly what he's doing, whether or not he's taking rapamycin or not. I certainly can't speak for him.

But at present, I don't take rapamycin. Why don't I take rapamycin? Well, I don't take rapamycin because, at least to my eye, the data at present don't justify that for sake of increasing lifespan. That is not to say that rapamycin isn't an effective drug for the treatment of various cancers and for other purposes.

But for me, at this point in time, I just don't see a good reason for me to take rapamycin relative to some of the, let's just say, substantiated potential side effects of rapamycin. It is a drug that, I think, can be taken safely under certain conditions but has enough of a side effect profile that I'm not interested in taking it for sake of increasing lifespan at this time.

So no metformin, no rapamycin for me right now, perhaps in the future. I've listed out the things that I'm perfectly willing and happy to do-- grape seed extract, NR and NMN, the occasional NAD infusion to increase NAD directly. And for the time being, I've decided to stay away from metformin and rapamycin. But, of course, any and all of that could change going forward depending on the data that are published and my own experiences.

As a final point on this, I want to again emphasize that the foundation of a quality life and a long life is most certainly going to come from the basics, perhaps the most fundamental and important of which is to get sufficient amounts of quality sleep each night. We know that not doing that can, indeed, reduce your lifespan, if not directly, then certainly indirectly by increased number of accidents and certainly being far less happy and energetic during the day. So that's fundamental.

Also-- and this is very important to emphasize. And here, I'm essentially borrowing the words straight out of Dr. Peter Attia's mouth. So forgive me, Peter. This won't be nearly as eloquent or succinct as Peter would make it. But it is very, very clear that at present, there is no supplement or drug for increasing longevity that even comes close to the known improvements in health metrics that relate to longevity that come from getting quality sleep and especially from getting sufficient amounts of quality exercise.

So that means both a combination of cardiovascular exercise, a minimum of 180 to 220 minutes of so-called zone 2 cardio per week. So that's cardio that you can carry out while still maintaining a conversation. But should you increase the intensity any more, you would have a hard time completing your sentences. But in addition to that, also doing some VO2 max work, so getting your heart rate way, way up at least once per week.

And also, of course, doing resistance training, either with weights, machines, or bodyweight, doing that at sufficient intensity, six sets minimum per body part per week, to maintain not just muscular size and strength but, equally important, perhaps even more important, maintaining nerve to muscle connectivity, which correlates with cognitive function and a number of other important longevity metrics.

So, again, exercise, sleep, quality nutrition, quality social connection, which means eliminating, as best you can, toxic social connection and increasing quality social connection, people that you like and enjoy spending time with and feel enriched by, stress modulation, all of these things are so key, and, of course, getting morning sunlight. All of those things combine to have a huge outsized effect compared to anything that you could take in pill capsule or infusion.

So before even considering taking any supplement or drug to increase your longevity, or even for increasing vitality for that matter, get those basics of sleep, sunlight, nutrition, movement, stress modulation, or stress control, I should say, and relationships down. Get those right, and get that morning sunlight to set your circadian rhythm because, of course, your circadian rhythm is what anchors it all.

And I'd be completely remiss if I didn't emphasize yet again that any time you're thinking of adding a supplement or removing a supplement from your regimen or adding a prescription drug or removing a prescription drug, you absolutely should consult your board-certified physician.

The next question is about working memory. The question is, "What is working memory? What are the mechanisms behind working memory? And how can I improve my working memory?" Well, first off, this is a fantastic question that everybody should be aware of the answers to because working memory is so critical for every aspect of everyday life, as well as for learning new information. And it has direct correlates with not just things like IQ and overall levels of cognition, but, indeed, it relates to our longevity of cognition, that is, how well or how poorly we are holding onto our flexible brain function.

So for those of you that don't know, working memory is our capacity to keep certain amounts of context relevant information online. And when I say online, I don't mean on the internet or on social media. I mean online within our own brains. One example of working memory is your ability to remember a string of numbers for sake of being able to, for instance, dial a phone number a few minutes or maybe even an hour later or perhaps to remember a door code or the code to a combination lock.

So, for instance, you might be going to a new apartment or a home or visiting the home of a friend. And you might say, is there a gate? And they'll say, yes, there's a combination lock or a code for the front door, and that code is 76813. And so you'll remember 76813, 76831. And most people will need to write that down. But some people can keep that information online in their so-called working memory.

So this is information that generally has relevance for the particular context that you happen to be in or will soon be in but that often, not always, is discarded in terms of not needing to store it in your long-term memory. Now, working memory and long-term memory have a relationship. Some things within our working memory get passed to our long-term memory, but much of it does not.

So working memory is at play all day, not just in remembering strings of numbers but perhaps also in remembering specific names of people that you're going to interact with in a given environment. Perhaps you walk into a meeting or a classroom. You're introduced to this person, that person, and another person. And your hope is to remember their names. And you may or may not need to remember their names long term. But you need to keep that information online in order to be able to refer to them by first name within that particular context.

And a third example of working memory is your ability to call to mind specific types of information from within a larger batch of information. In fact, this is an opportunity for me to refer to a specific task that's used in a large number of studies, both psychological studies and neuroscience studies, of working memory. And that's the reading span task or the sentence span task. And it's fairly straightforward to understand.

So in this task, you would hear or read some specific sentences. So the sentence might be, "The other day, I went to the market, and I searched for organic cucumbers, grass fed steak, and rice from a particular part of Southeast Asia." So that's a sentence that perhaps you could recite back to me in a moment if you were asked to do that. But that's not what the task asks you to do.

The task asks you to then listen to another unrelated sentence, which is, "Lately, I've been searching for an automobile. I've always driven a Toyota 4Runner"-- which, by the way, folks, is true-- "but I'm thinking about getting a sedan this year." And then there might be a third unrelated sentence, so a sentence with a totally different context, which is, "I looked the other day on my phone, and I realized that I'm spending more than 90 minutes in web browsing every evening between the hours of 6:00 p.m. and 9:00 p.m.," which, by the way, folks, is not true.

Okay, so I just said three sentences, and each of those sentences conveys a certain amount of information. It might seem rather mundane, but that's how these tasks go. And then the task is the following. Can you remember the final word of each of the sentences that I just said? Okay, well, I'm guessing you probably could not.

For those of you that can remember the final three words of each of those sentences, well, congratulations, you have a quite active working memory. But the way the task is typically done is that before I would tell you those three sentences, if I were the one running the study, that is, I would ask you to pay careful attention to the words coming at the end of the sentence.

I wouldn't tell you that you need to pay attention to the last word. But I tell you to pay attention to the ending of the sentence. And I'd probably also ask you some questions about, which items did Andrew go pick up at the market? If you recall, there were some organic cucumbers, some grass fed meat. You might also be asked to recall which specific cars or trucks Andrew currently drives versus what he's considering purchasing.

So, again, it's the 4Runner that I drive and have long driven 4Runners versus the sedan that I'm considering buying, which is, by the way, not true. I like my 4Runner. I don't plan to replace it any time soon. In any event, while these tasks focus on fairly innocuous and somewhat uninteresting information, they are complete sentences that have contextual coherence. That is, the sentences make sense. They're not nonsense sentences, but they're not related to one another.

But unless you're really cued to pay attention to the final words of the sentence, chances are you're not going to remember that final word of the sentence because more of your attention is focused on taking in the overall context and the different nouns and verbs within the sentence and within the context of a farmers' market or a car purchase and things of that sort.

Okay, now, for most people who have normal cognition, meaning not suffering from traumatic brain injury, dementia, et cetera, who hear six such sentences in one of these studies, and before the study begins, they are cued that they are going to need to remember the final words of each of those sentences, on average, people can remember four out of six of the final words from those sentences.

Some people remember two. Some people remember six. There are the people who occasionally remember just one or even zero and everything in between. But the average turns out to be four. And in some of these studies, people hear many more sentences. In other studies, they hear a few less but generally not fewer than six sentences. Okay, so that's the in-laboratory working memory task, or I should say it's just one of the many in-laboratory working memory tasks.

But it has great relevance for everyday activities, such as if you're headed home from work or school and you need to pick up a few things, you have to make sure that you don't get distracted by what's going on on your phone or invitations that you might receive or different routes that you could take home if, in fact, you need to take the route home and pick up something specific at the store. And then once you're in the store, you need to pick up the specific thing you need to get.

Now, sure, you might pick up a few other things. But you have to make sure that none of those things is so attention-grabbing that you forget the working memory task, that is, to pick up the initial item that you went to the store to get. Okay, so working memory is weaved through every aspect of everyday life. And it becomes especially important when we are trying to pay attention to and learn new information. But, indeed, it's also important for everyday functioning.

Not surprisingly then, working memory tasks are also extremely important for probing levels of cognitive function, and deficits in working memory are prominent in people who have frontal lobe damage, so TBI-- Traumatic Brain Injury-- that focuses on the frontal lobes-- I'll explain why that is in just a few moments-- as well as people who have age-related cognitive decline or in Alzheimer's, which is an exacerbated or accelerated degree of age-related cognitive decline and in a number of other conditions, including attention deficit hyperactivity disorder, which, if you listened to the two episodes I did on ADHD, doesn't always include the hyperactivity element. Some people just have attention deficit disorder.

Okay, so working memory is very important in everyday life. And now you have some understanding of the way that working memory is probed in the laboratory and how that resembles the real world use of working memory. So that leads us to the question that was asked about, how does working memory work? Or what are the mechanisms underlying working memory? Now, that's a vast discussion unto itself. And I will, indeed, do an entire episode of the Huberman Lab podcast about working memory.

But for right now, let's just take about three minutes-- yes, only three-- and talk about some of the neural circuits and neurochemicals that support functional working memory. So working memory relies on a number of different distributed brain areas that we call a neural circuit. But it relies heavily on the activity of the frontal lobes. The frontal lobes are neural real estate that reside just behind the forehead.

You have a frontal cortex on each side, left side of your brain and the right side of your brain. More specifically, you have a prefrontal cortex, which is the anterior most or the most forward part of your frontal cortex that does, indeed, reside right behind your forehead. And it has, as I mentioned before, two sides, a left side and a right side. And working memory relies on neurons in the prefrontal cortex and, in particular, neurons within the right prefrontal cortex.

Now, the prefrontal cortex doesn't carry out the job of working memory alone. It needs inputs and outputs from and to other brain areas. And one of the key inputs to the prefrontal cortex that allows working memory to function smoothly are the dopaminergic, that is, the dopamine neuron inputs that come from further back and deeper in the brain into the prefrontal cortex. So as I'll soon describe, prefrontal cortex and dopamine action within the prefrontal cortex is absolutely critical for working memory.

Now, to be clear-- and this isn't just for the aficionados and the career neuroscientists out there-- dopamine input to the prefrontal cortex and the right prefrontal cortex in particular is critical for working memory. But there are other critical brain areas for working memory as well, including key areas within the so-called thalamus. So this is an egg-like structure deep within the brain that provides input to the prefrontal cortex and can adjust or modulate the activity there. So I don't want to give the impression that it's just prefrontal cortex and dopamine.

There are other critical structures involved, and they're all acting together in concert to allow you to keep certain types of information online in a context dependent way. And as you're hearing about all of this and you're thinking about the example of working memory tasks in the laboratory that I described earlier, if it all feels like a bit much, like it's a lot of information, well, guess what? You're using your working memory. You're trying to hold online all this information that presumably is new to a good number of you.

Now, some of the most important work on working memory and prefrontal cortex comes from the laboratory of a guy named Mark D'Esposito, who is at the University of California, Berkeley. He's actually a neurologist by training. And a few years back, he did some really important studies on the role of dopamine in working memory.

Now, first off, let's just recall what dopamine is. Dopamine is a neuromodulator. It's often referred to as a neurotransmitter, and that's fine. You can call it a neurotransmitter if you want. But a neuromodulator, as the name suggests, modulates the activity of other neural circuits. Now, there are some key studies on dopamine that the D'Esposito lab and other laboratories did, which really pinpoint the key role of dopamine in working memory function.

So I'm just going to mention those results now. I will also provide a few links to the relevant studies in the show note captions if you'd like to dive deeper. And as I mentioned a few minutes ago, I will be doing a full-length Huberman Lab podcast episode about working memory, mechanisms of working memory, and tools for working memory. But that's also what we're talking about now.

So the first thing to know is that working memory can be measured in the laboratory. The other thing that can be measured in the laboratory are people's baseline levels of dopamine. This is done with a technique called Positron Emission Tomography, or PET, that involves injecting people with an innocuous dye that then allows researchers to put them into a specific type of machine which allows them to get images of their brain and look at the reservoir, the available dopamine that has not yet been deployed for a working memory or other task.

And what one discovers is that people who, on average, have higher levels of baseline dopamine perform better on working memory tasks of the sort that we talked about earlier relative to individuals who have lower levels of baseline dopamine. So there's a strong correlation-- none of this is causal yet, or at least I haven't given you the causal evidence yet. But there's a strong correlation between baseline levels of dopamine and ability to perform well, that is, average or above average, on working memory tasks.

In addition to that, there's what's called a double dissociation. So I just told you that people with higher levels of baseline dopamine perform better on working memory tasks. Well, it also turns out that people who have lower levels of baseline dopamine perform less well on working memory tasks, which you might think is the same thing as what I just said but looked at it from the other side of the coin.

But, indeed, in separate studies where people have had their baseline levels of dopamine depleted either by injury because they happen to have had an injury out in the actual world-- they're not inducing injuries in humans in the laboratory, of course-- but a brain injury such as a car accident or a construction injury. And by the way, we always hear about concussion and traumatic brain injury, and everyone immediately thinks football, rugby, which, of course, are prominent sources of traumatic brain injury and CTE. But most traumatic brain injury doesn't come from sport. Most traumatic brain injury comes from things like car accidents and construction work and things of that sort.

So people who have their baseline levels of dopamine depleted by traumatic brain injury perform less well on working memory tasks. In addition, as we all age, indeed, as we all age, baseline levels of dopamine in key areas of the brain, such as the striatum, also decline over time. And what one observes is not just a decline in baseline levels of dopamine but a corresponding decline in performance on working memory tasks.

Moreover, if people do take a drug that depletes baseline levels of dopamine, this unfortunately does occur in various drug users who inadvertently take a drug that they thought was one type of illicit drug or street drug, and it turns out to be a chemically modified version of that-- this really does happen-- or in chronic, for instance, methamphetamine users who deplete their baseline levels of dopamine, or in chronic cocaine users who deplete their baseline levels of dopamine, they, too, have diminished performance on working memory tasks.

So on the one hand, we know that high levels of baseline dopamine are associated with better performance in working memory tasks. And we also know that anything that takes people below normal baseline of dopamine levels also will diminish performance on working memory tasks. So there's a bidirectional relationship between baseline levels of dopamine and performance on working memory tasks, this task that greatly resembles everyday functioning in terms of how you need to get about your day as well as your ability to learn and retain critical new information.

Now, the evidence that dopamine is causally related to working memory is really spectacular. And it really comes from the work of Mark D'Esposito and colleagues, showing, for instance, that if undergraduates whose baseline levels of dopamine have been measured take a drug-- in this case, the drug is something called bromocriptine. Bromocriptine is a drug that's used to elevate dopamine in Parkinson's patients. But the subjects in the study I'm describing were not Parkinson's patients. Rather, these were undergraduates at UC Berkeley.

And if they take bromocriptine, they perform better on working memory tasks for a short while, meaning for the duration of the task. It's not indefinite. They didn't get a permanent increase in working memory function. However-- and this is a very important however-- there were essentially two groups that fell out or that were observed within this particular study. One group had low levels of baseline dopamine when they came into the study.

Now, that turned out to not be the consequence of any traumatic brain injury or methamphetamine use or cocaine use. All of those things were ruled out. Rather, these individuals had slightly but still significantly lower baseline levels of dopamine. And that simply reflects the fact that in the general population, even in the absence of dementia, the absence of illicit drug use, and the absence of any kind of insult or injury to the brain, people are walking around with different baseline levels of dopamine.

Now, of course, those baseline levels of dopamine could be different according to different levels of self-care, how much sleep they got the night before, whether or not they exercise regularly, things all known to basically re-up or to fill back up the reservoir of dopamine in the brain. In fact, in a few minutes, I'll talk about some tools and techniques that can do that. I've talked about some of these in previous podcasts. But keep in mind that some of these students simply had lower levels of baseline dopamine when they showed up to the study.

And none of those low levels could be attributed to anything dramatic or acute, such as an injury or neurologic disease. Other individuals in the study had higher levels of baseline dopamine when they walked into the study the very first day. And at least as far as we know, none of those elevated levels of dopamine were the consequence of anything pharmacologic because, of course, they ruled out anyone that was taking drugs for, say, the treatment of depression or ADHD in order to elevate baseline levels of dopamine because, indeed, many of those drugs do just that.

But what this study discovered was absolutely fascinating. What they found is that for individuals that have slightly lower levels of baseline dopamine at the outset of the study, increasing the amount of dopamine in their system using this drug bromocriptine-- although it turns out other drugs that increase dopamine, such as L-dopa and things like apomorphine, can do the same thing. When they then increase their levels of baseline dopamine, they went from performing less well to performing significantly better on working memory tasks.

Okay, so put differently, if your baseline levels of dopamine are slightly low or low, increasing that level of dopamine will allow you to perform better on a working memory task. And these were quite significant effects, meaning the performance on the working memory task went way up. So, for instance, in the sentence task that we talked about earlier, it might be that one of these individuals was remembering two out of the six of the final words of those sentences that they had heard in that task.

They would take bromocriptine, and then they would go from remembering two of the final words to remembering anywhere from four to six. I just gave an example that was just a hypothetical example. There was a range of improvement in these individuals who initially had low levels of baseline dopamine and then took bromocriptine and thereby increased their levels of baseline dopamine.

Contrast that with the individuals who, when they showed up to the study, had high levels of baseline dopamine. Recall these are the people that are going to take that working memory task. They haven't yet taken any drugs. So they're not taking bromocriptine. They haven't taken apomorphine. They haven't taken anything to increase their baseline levels of dopamine. Rather, their baseline levels of dopamine are already significantly higher than others in the group.

And when those individuals take bromocriptine or apomorphine or another drug that further increases the levels of dopamine in their brain, well, their performance on these working memory tasks actually goes down. That's right. It goes down. And this is well supported by studies in nonhumans primates as well as studies from other laboratories in humans, where you do essentially a dose response curve to bromocriptine.

This involves bringing individuals into the laboratory. Sometimes their baseline levels of dopamine are measured. Sometimes they're not. But you give people different dosages of bromocriptine, and you measure how their working memory is when they get the placebo, so zero milligrams of bromocriptine. You get them into a working memory task. You measure their performance.

And they come in a separate time or maybe later that day. They do the working memory task after taking a small dose of bromocriptine versus a medium versus a large dose of bromocriptine. And, of course, there are adequate controls because, of course, of course, of course, you expect that individuals will get better at working memory tasks due to repeat effects. Doing something more often, you generally get better at it.

So all of that is controlled for. In fact, if you think about it, it's pretty easy to control for. You just look at the normal improvement in somebody who thinks that they're getting increasing dosages of a given drug over time, but, indeed, they're just getting the placebo. Or just somebody who comes in and does those working memory tasks four times in a row, you look at the average improvement. You do that in a group of people. And then you compare that to people that actually got increased levels of bromocriptine with each successive experiment.

Or even better, you'd have people get zero milligrams of bromocriptine. Then perhaps the next time, they get a high dose or a medium dose. You'd make it random. Then the next time, a low dose. And so by doing that in a sufficient number of individuals, you can come up with a very firm conclusion.

And, again, what I'm about to say is the aggregate conclusion of a large number of studies now done in humans with neuroimaging and PET, MRI, animal models, and on and on. And basically what we can say is that there's a sweet spot for dopamine levels and working memory. Yes, it is true that higher levels of dopamine correlate with improved working memory. It's also true that lower levels of dopamine correlate with poorer working memory.

It is also true that low levels of baseline dopamine, that, when elevated pharmacologically, can improve working memory. But it is also true, as I mentioned before, that if you have high levels of dopamine to begin with, further increasing those levels of dopamine will actually diminish your performance in working memory and, by the way, in a number of other different cognitive tasks as well.

Okay, so now you know what working memory is, you have some understanding of the underlying mechanisms, and you have an understanding of some of the things that can modulate-- again, I'm using that word because dopamine is a neuromodulator-- some of the things that can modulate working memory. Now, as you recall, I was asked, how can we improve our working memory?

So it should be obvious that for those that already have lower-- and notice I said lower as opposed to low because it's all relative. There's a distribution of baseline dopamine levels out there. But for those people who have lower baseline levels of dopamine, increasing levels of dopamine, even transiently, will improve working memory.

Now, how do if you have lower, medium, or high levels of baseline dopamine? Now, as far as I know, there are no inexpensive and also accurate ways to measure your baseline levels of dopamine. This is unfortunate. And frankly, I don't have a solution to it. But the good news is you don't really need to know your baseline levels of dopamine in order to glean some important tools for improving your working memory.

But before we get into those tools, I'll just say that if you were, oh, so curious as to what your baseline levels of dopamine really were or are, you would need to go into one of these positron emission tomography scanners. And, of course, that would need to be done by a neuroscientist or a clinician who had the technical expertise and approval to do so. I wish that there were blood tests or other sorts of bodily tissue or fluid tests that could give you really accurate readouts of baseline levels of dopamine in the relevant brain structures.

But as far as I know, no such tests exist. There are tests out there that will take your blood or other samples from your body and give you a number back as to what they presume your baseline levels of dopamine are. But when I look at those tests and I look at the tissues they rely on and the metabolites that they're examining, none of them seem accurate enough to give you a clear picture as to whether or not you have low, medium, or high baseline levels of dopamine in your striatum, which is the area of the brain that's going to be relevant for the working memory task that we're describing here. So that's unfortunate.

I, for one, would love to know what my baseline levels of dopamine in my striatum are without having to go into a PET scanner. And I'm sure many of you would as well. I think this represents a really key niche and opportunity for the development of technology to measure levels of dopamine noninvasively. And hopefully those techniques will come about in the next few years. Maybe one or several of you will come up with those technologies because I think there's a real interest and wish.

Now, working memory tasks, however, are noninvasive, and there are a number of good ones online that you can take without having to participate in a given study. I think most people have a general sense of whether or not their working memory is better or worse than it was, say, a year ago or a few years ago. I know a common concern of many people, especially people over the age of 40, is whether or not they're losing their memory.

A lot of people over the age of 40, and sometimes even younger, will get the so-called tip of the tongue phenomenon, where, in your mind, you know what you want to say, but you don't remember the exact words or the example that you're thinking of in what seems to be your unconscious mind. So it's sort of right there, but you can't access it.

That is perfectly normal. And provided it doesn't hinder your everyday functioning, I wouldn't be terribly concerned. However, if you're finding that you're forgetting things far more often, you're forgetting where you are or where you were going when you walked into the store, what you were there to get, those are matters for concern. And you should definitely talk to a neurologist because those are deficits in working memory that, unfortunately, in some people, really accelerate with age or accelerate after traumatic brain injury or for whatever other reason.

It's also worth mentioning that anything that damages dopaminergic neurons, things like methamphetamine use, things like traumatic brain injury, so getting repeated concussions or even one severe concussion, can permanently limit the total number of dopamine neurons or dopamine output. So those are obviously things that you'll want to avoid. And if you have had a concussion, my first suggestion in the list of suggestions of things to avoid and to do is to not get another one, okay? So that's very important.

But those are all the do not. And now I'd like to focus on to-dos, meaning the things that one can do in order to increase baseline levels of dopamine. And these are all tools that are gleaned directly from the peer-reviewed scientific literature. So first and foremost is the one that I always come back to because it is, oh, so critical for every aspect of mental health, physical health, and performance. But it's also well established to re-up or replenish levels of not just dopamine but other neuromodulators in the brain that are required for working memory and other key aspects of cognitive function.

And that is to get sufficient amounts of quality sleep each night, or I should say as many nights of your life as possible. And if you're not going to get quality sleep on a given night, hopefully it's for good reasons, festive reasons, or it's for absolutely necessary reasons, like raising children, et cetera. And the reason I say that, the reason I say all of that, is because none of us get sufficient amounts of quality sleep every single night of our entire life.

Things come up. Life happens. Emergencies happen. Great nights out where we decide to study all night. I did plenty of that. Or party with friends really late. Look, that's just part of life. And certainly raising children for many of us is part of life. But all of us should strive to get sufficient amounts of quality sleep as many nights of our lives as possible.

So for most people, that's going to be six to eight hours. For some people, it will be as little as five. For others, it will be as much as 9 or 10, especially teenagers and when we're sick. People have different sleep requirements. So figure out what those are, and figure out how to get sufficient amounts of quality sleep for you as many nights of your life as possible.

And I've done multiple episodes of the Huberman Lab podcast on this, the "Master Your Sleep" episode. I did the "Perfect Your Sleep" episode as well. I also did a "Perfect Your Sleep" episode with expert guest Dr. Matthew Walker. And we have our zero cost tool kit for sleep that's available at hubermanlab.com. So all of those resources contain timestamps that can bring you to specific tools and things to really dial in your sleep. So that's the first one. And I'd be remiss if I didn't mention it.

The next thing that we know can dramatically, that is, that can cause statistically significant increases in baseline dopamine within the striatum, the very structure for which improvements in working memory occur when you have higher levels of baseline dopamine, is non-sleep deep rest, a practice that I've talked about extensively on the podcast. But if you haven't heard me talk about, this is a completely zero cost behavioral tool, so no pill, no supplement, no drug required.

Non-sleep deep rest, or NSDR, involves lying down for anywhere from 10 to as much as 60 minutes. Some people do it for as long as 60 minutes. But anywhere from 10 to 30 minutes is typical NSDR. And you engage in some long exhale breathing, which tends to relax your nervous system by activating the so-called parasympathetic arm of your autonomic nervous system, a big nerdspeak mouthful of words, which basically mean long exhale breathing, especially when done through pursed lips and very slowly in a controlled way. Really lower your heart rate and cause relaxation.

You do a sort of a body scan. This practice, NSDR, doesn't involve any mantras, any intention. So there's nothing mystical about it. It's really a self-directed deep relaxation protocol that brings your mind and body into a state that is quite similar to rapid eye movement sleep. And the reason I say that is that your body is very still, but your mind remains active. Your mind is relaxed, if there is such a thing. So this is so to speak, right? No one really knows what, quote unquote, "relaxed" mind means.

But you're not anticipating future events. You're really focused on what's happening right then and there. And you are alert. You are awake while being deeply relaxed in the body. And you're doing that intentionally. And it's a practice that can, indeed, take some practice to get better at but that many people find from the very first time they do it is extremely relaxing and extremely replenishing. That is, it seems to replenish their cognitive and physical vigor when they exit the NSDR.

And that should come as no surprise because there are actually peer-reviewed data that I've talked about before on this podcast-- I'll provide another link to one of the papers in the show note captions here. But there are peer-reviewed data that show that NSDR, also sometimes referred to as yoga nidra, which means yoga sleep, although yoga nidra is slightly different, can increase baseline levels of dopamine in the striatum by as much as 60% as compared to the levels of dopamine prior to doing that yoga nidra aka NSDR.

Okay, so this is a very powerful tool. It's not weak sauce, as the kids say. This is something that can really increase your baseline levels of dopamine. And it's completely zero cost. I mean, it requires a little bit of time to do. You can access a NSDR script on YouTube by putting "NSDR Huberman." That one, as the name suggests, uses my voice. There are some longer NSDR scripts. Some of the ones that I use and that I like very much are the ones from Kelly Boys.

You can find some of those on the Waking Up app. You can also find those zero cost on YouTube, putting her name, Kelly, K-E-L-L-Y, separate word Boys, B-O-Y-S, NSDR. She has some 8-minute, some 20-minute NSDRs. And of course, there are other voices and sources of NSDR that are zero cost available on YouTube and elsewhere. As far as I know, these are all more or less equivalent.

They all accomplish more or less the same thing. I've been doing NSDR or yoga nidra as a consistent practice either first thing when I wake up in the morning if I felt I didn't get enough sleep the night before or sometimes in the afternoon or sometimes if I wake up in the middle of the night and I want to fall back asleep. Although more typically, first thing in the morning, if I didn't feel I got enough sleep the night before, I'll do NSDR or in the afternoon if I feel like I need to replenish my mental and physical vigor.

And as I described, that replenishment in baseline dopamine in the striatum is at least one of the mechanisms by which NSDR aka yoga nidra is likely to give us that sense of renewed physical and mental vigor. So it's a very powerful practice, again, completely zero cost, and one that I strongly encourage people to at least try and to incorporate if your goal is to improve working memory as well as to just improve baseline levels of dopamine for other purposes as well.

I've also talked before on this podcast about deliberate cold exposure. In fact, we did an entire episode about deliberate cold exposure. And we know that a cold shower or an ice bath or a cold plunge or a dip in a cold lake or ocean, indeed, causes a very significant increase in the release of epinephrine, adrenaline into our brain and body. But we also know, based mainly on one study, but now there are some additional studies as well, that it can increase baseline levels of dopamine significantly and for long periods of time, up to several hours.

Now, how great that increase in dopamine is and how long it lasts depends on a couple of different factors. What seems to be the general takeaway from those studies is that if the water is very cold, say somewhere between 35 degrees Fahrenheit and 45 degrees Fahrenheit, as little as 30 seconds or a minute or two minutes in that cold water induces those long lasting increases certainly in adrenaline but most likely in dopamine as well.

Other studies have shown that longer exposure to warmer temperatures, so putting people up to the neck into cool water. so high 50s or maybe in low 60-degree temperature water, for a longer period of time of 45 minutes to an hour can induce long-lasting increases in dopamine. Unfortunately, there aren't a lot of studies on this. So we don't know exactly how long in a given temperature one needs to go into cold water in order to induce these increases in epinephrine and dopamine.

But suffice to say that there are now several studies showing that if you get into uncomfortably cold, yet safe temperatures of water-- so this could be by cold shower, but more typically, it would be by immersion into cold water of some sort. Again, uncomfortably cold but safe. And I say that and I don't tell you 45 degrees because we all have different levels of cold adaptation and tolerance.

So for some people, 35 degrees is going to be manageable and safe. For other people, 45 degrees is manageable and safe. For other people, that's not manageable or safe and so on. You need to find a temperature that's uncomfortably cold for you but is safe, meaning that you're not going to send yourself into cold water shock or get a heart attack because, indeed, that is a possibility. It's a slim possibility unless you get down to those really cold temperatures, but it is possible.

So start on the warmer end of things and figure out what temperature is going to feel uncomfortably cold, meaning you want to get out, but you can stay in for anywhere from 30 seconds to maybe two minutes, and you can do that safely. And then, of course, the big increases in epinephrine and dopamine take place then. But it's really the fact that they persist for many minutes and, indeed, many hours after the deliberate cold exposure that is the reason why many people are using this tool as a way to get that elevated levels of alertness.

And here, of course, we're not just talking about levels of alertness but also the elevated feelings of mood. And presumably, if you're increasing circulating levels of dopamine, you're increasing working memory capacity. But-- and I must emphasize this-- to date, there is no specific study that has directly explored the relationship between deliberate cold exposure and working memory performance.

There are some studies that have explored how an amino acid, which we're going to talk about in a moment fairly extensively, L-tyrosine, is the precursor to dopamine, can mitigate some of the deficits in working memory performance that are caused by cold exposure. That's right.

When people are really cold, in those moments when they're very cold, regardless of whatever neurotransmitters have been increased and are circulating about, their working memory capacity actually goes down while they're in the deliberate cold exposure. However, there are some data that point to the idea that after the deliberate cold exposure or anything else that increases dopamine levels, that people's working memory capacity increases, as we discussed before.

So what does this all mean? Certainly get as much quality sleep as many nights of your life as you possibly can. And make sure you're getting enough of it within a given night. Second, tools like NSDR, as far as the data tell us, are excellent for increasing baseline levels of dopamine-- zero cost, very safe. Provided you're not lying down in the middle of the road, I can't imagine the NSDR would be unsafe for you.

Third, anything that's going to spike your adrenaline and dopamine, in principle, could improve your working memory because of the relationship between dopamine and working memory. But to my knowledge, there's no study that's used deliberate cold exposure specifically as a tool to improve working memory.

And for that matter, a run or going cycling or swimming or resistance training for an hour also will increase epinephrine and dopamine, although-- and this is an important although-- the degree and duration of dopamine increase that's been demonstrated for deliberate cold exposure is very impressive relative to the degree and duration of dopamine release that's caused by exercise.

This is important because a number of people will say, okay, fine, deliberate cold exposure increases dopamine but so does exercise. So why not just use exercise? The kinetics, the time course of the dopamine release that comes from deliberate cold exposure is really what makes it an intriguing tool that, of course, isn't a replacement for exercise but you might use as an augment for exercise.

Now, with that said, exercise because it does have the capacity to increase epinephrine and dopamine, especially exercise sessions that are an hour long or less and that are fairly intense, so getting your heart rate way, way up for you. Doing resistance training that brings you close to failure on individual sets or to failure on individual sets for you, whatever that represents, can also increase dopamine perhaps transiently but perhaps also significantly enough to improve working memory in the hours post.

Now, if you're exhausting yourself with exercise, your working memory capacity will definitely go down. We know that there is a strong circadian rhythm to working memory capacity, so much so that if you look at people's ability to perform working memory tasks in the first eight hours after waking, it is significantly greater than their capacity to perform the same working memory task 9 to 16 hours later and certainly 16 to 24 hours after having been awake. Because 16 to 24 hours after you woke up, you should be asleep. And we know that your working memory is best in the first third of your circadian, that is, your 24-hour cycle, so those first eight hours.

Now, I mentioned L-tyrosine. L-tyrosine is the amino acid precursor to dopamine. And it, of course, can be derived from foods. Rather than me listing off which foods are high in L-tyrosine, you can simply look that up online. It's very easy to do. And as always, you're mainly going to want to get your L-tyrosine from quality food sources in order to make sure that you are manufacturing enough dopamine in your brain and body. Yes, dopamine is also made and used in neurons of your body, not just within the brain.

But some people opt to further increase their levels of dopamine not just for sake of improving working memory but that included. And they do that, and there are, indeed, peer-reviewed studies exploring the effects of L-tyrosine at improving working memory. Now, I should say that these studies generally have relied on very high doses of L-tyrosine in order to do that, dosages that, frankly, I'm not comfortable taking myself.

So these are dosages well in excess of four to five grams. So for me, that just makes me cringe. I will occasionally-- I wouldn't say routinely. But I'll occasionally take anywhere from 500 to 1,000 milligrams of L-tyrosine alongside 300 to 600 of alpha-GPC if I'm really going to try and focus very intensely on some material that I want to learn. But I don't do that every time I sit down to try and learn some new material. I'll sometimes also do that before a particularly hard resistance training workout.

But I don't do it every time. I'm not a believer in always relying on anything like energy drinks or supplementation to really boost neuromodulators in the brain for every single workout. I like to use it maybe every third workout or maybe every other learning session. And certainly, I would only take it early in the day, never later in the day because of the increase in autonomic arousal those can cause can sometimes disrupt sleep.

So for me, as little as 500 milligrams of L-tyrosine, maybe combined with a cup of strong espresso or yerba mate, is sufficient. For other people, they may require more. There seems to be a lot of variability in terms of how people respond to L-tyrosine in terms of its ability to increase dopamine in the brain and working memory function. And this is really important. So for instance, if you went to examine.com, a terrific website that, by the way, I have no financial relation to whatsoever-- if you go to that website and you put "working memory" into the search function, it will take you to the so-called human effect matrix.

And top or near the top of that list, it'll say L-tyrosine, if taken in sufficient dosages, can cause a mild but significant improvement in working memory and some other cognitive tasks as well. They also list off some things like L-theanine, which can do the same. And they'll list off some things like cannabis, which, no surprise, actually causes deficits in working memory. I don't think anybody should be surprised about that statement. In any event, the dosages that were used in most, not all but most of those studies of L-tyrosine are quite high, far higher than I would ever want to explore personally.

So when it comes to supplementation, my suggestion is first focus on behavioral tools before exploring supplementation at all. Make sure that you're doing all the right things correctly. We talked about some of them already. And then if you're going to explore supplementation, to go about it scientifically and gradually so that you don't just pick a number out of a study and take that amount and just kind see what happens.

Rather, it's far more beneficial to figure out the lowest effective dose for you in a given context. And yes, that involves some exploration. But if anything, it's more cost effective. And certainly, if your goal is to improve your working memory, I think it would be far better to know what that threshold is of L-tyrosine intake, of course, done on a background of other behavioral tools, adequate sleep, et cetera. You're not going to eliminate a bad night's sleep by taking L-tyrosine. You might offset it slightly.

But chances are you're going to get yourself into more discomfort than anything else. But if you're sleeping well, you're already doing your NSDR, you're doing other behavioral tools to improve your dopamine and working memory and you want to explore L-tyrosine supplementation, well, then start with a low dosage, maybe 500 milligrams, and then ratchet it up across a couple of different sessions and find the sweet spot for you.

And, of course, that's also going to be safest because, like anything, L-tyrosine does carry some risks. It's fairly low risk for most people. You'll have to talk to your doctor to decide if it's at all right for you. But if you can get away with taking less as opposed to more, I see that as advantageous. Likewise, before you start combining L-tyrosine with alpha-GPC and a bunch of other things, I suggest trying those individually and seeing what works best for you, or perhaps they don't work for you, or you don't like the way that you feel when you take them.

Now, keep in mind what I said earlier, which is for those that already have high levels of baseline dopamine, further increasing dopamine will diminish-- that's right-- will diminish, not improve your working memory. So you want to keep that in mind, too. And I think that's yet another reason for, if you're going to explore supplementation with things like L-tyrosine, to go about that starting with the lowest effective dose and increasing it gradually if and only if you are seeing successive improvements in working memory.

And then in terms of other tools to increase dopamine for sake of improving working memory, well, if you recall, the studies from the D'Esposito lab and other laboratories relied on these drugs that initially were developed for the treatment of Parkinson's, things like bromocriptine, L-dopa, and so on. And those drugs are out there. They do require a prescription.

And of course, of course, of course, I'm not suggesting that you take prescription drugs for a purpose that they are not prescribed to you for. You'll need to talk to your physician. I recommend only getting those drugs through legal sources that are for specific need. Indeed, several neuroscientists have gone on record saying that it's somewhat surprising that there are drugs out there like bromocriptine that we know can improve cognitive function, for instance, in people with traumatic brain injury or other forms of dementia, and yet those drugs are not generally prescribed for purposes of improving cognition.

And that reflects a number of things about the medical profession and about the pharmaceutical industry. And we don't really have time to get into any of that right now. I know this frustrates a number of neurologists and psychiatrists and others. I'll just say that. And maybe we'll get back to that topic at a future date. But these drugs do have the capacity, of course, to potently increase dopamine. And the ones that you hear the most about are bromocriptine, apomorphine, and L-dopa.

Now, those are prescription drugs. There is a supplement that perhaps some of you have heard of, which is mucuna pruriens, which, at least by chemical composition, is 90% or more L-dopa. So this comes from actually a velvety bean. I always find this so interesting, that there are these plant compounds out there in the world that have or are enriched for things like L-dopa. So mucuna pruriens is basically L-dopa. That's a nonprescription source.

I personally have tried mucuna pruriens as an experiment to increase dopamine. I found it to be very stimulating, meaning it really increased my levels of alertness and focus. But it led to a big crash afterwards. Some people like macuna pruriens. Some people get bromocriptine or apomorphine or L-dopa from a licensed physician and can take that as a way to improve cognitive function, although that's the more rare practice. Most physicians aren't going to prescribe those drugs for that purpose.

That said, they will improve working memory, as demonstrated in the work by D'Esposito and others. And then, of course, there's the entire class of drugs, most of which are amphetamines or similar, that are used to treat or, I should say, are prescribed for ADHD, Attention Deficit Hyperactivity Disorder, things like Adderall, Ritalin, and Vyvanse. Keep in mind that Ritalin is quite different in chemical composition and the way it affects the brain from things like Adderall and Vyvanse.

I talked a lot about each of these drugs in the episode I did on Adderall, Vyvanse, ADHD, et cetera. You can find that at hubermanlab.com. All of those drugs, with the exception of Ritalin, which is methylphenidate, are essentially amphetamines. So believe it or not, dioxin, which is a prescription drug, is methamphetamine, which is prescribed in some cases for ADHD. That is not to say people should take methamphetamine for ADHD.

In fact, dioxin is only used in the rarest of cases for ADHD. And when it's used, it's used at exceedingly low dosages compared to the dosages that are used recreationally. Adderall, Vyvanse, as many of you know, are well sought after these days. There's actually a shortage of these drugs. What do these drugs do? Well, they are amphetamines of some sort. They're different types of amphetamines chemically.

But they increase dopamine and epinephrine, adrenaline. And they tend to do that to varying degrees, depending on whether or not you're talking about Adderall or you're talking about Vyvanse or you're talking about some of the other amphetamine drugs for the treatment of ADHD. Now, it's well known that Adderall, Vyvanse, and methylphenidate, Ritalin, can improve working memory, not just in kids with ADHD but also adults with ADHD and, yes, even in people that don't have ADHD.

But that is not to say that you should run out and start taking those drugs nor do I recommend that you explore taking drugs like bupropion, which is sometimes called Wellbutrin, which is another way that people increase dopamine and epinephrine to improve cognitive function. It's an antidepressant. But people do take it to improve cognitive function. Similarly, they take things like modafinil, which is technically not an amphetamine, to improve cognitive function.

So there are a bunch of prescription drugs out there that increase both dopamine and epinephrine. And this is the flurry of drug names that I've been giving you for the last two or three minutes. A number of people will, indeed, experience improvements in working memory when they take those drugs at appropriate dosages. But, of course, all of them come with risks. None of them should be taken without prescription. And I do think it's important to point out that all of those drugs increase both dopamine and epinephrine.

And in the studies of working memory where particular pharmacologic compounds were used to improve working memory, the ones that we talked about earlier, those drugs were specifically selected because they increased dopamine but norepinephrine. So they were used to isolate dopamine and its effects on working memory. And I don't have time to go into it in a lot of detail, but suffice to say this.

The very same studies that looked at how increasing or depleting dopamine would impact working memory-- of course, now you know what the results of those were. When you increase dopamine, working memory improved if baseline levels of dopamine were initially low. If baseline levels of dopamine were initially high, increasing dopamine degraded working memory. But in all cases, regardless of whether or not you had low or high levels of baseline dopamine to begin with, reducing the available dopamine stores caused deficits in working memory.

Now, the scientists that did those studies explored whether or norepinephrine, adrenaline, had a similar effect. These are good scientists. They didn't just look at dopamine. They looked at epinephrine, serotonin, and a bunch of other things, too. And guess what? Increasing or decreasing epinephrine did not have the same effect. It did not alter or modulate levels of working memory. It could modulate your fatigue threshold, that is, how long you could do a working memory task. But it did not modulate performance in working memory tasks.

Why do I tell you this? Well, if you opt to take a drug that increases both dopamine and epinephrine and you're expecting it to improve working memory, it's very likely not going to have the same level of potent improvement on working memory that taking a drug or a supplement or my preference. Before exploring any of that, please, and, of course, always refer to your doctor when thinking about drugs or supplements, taking or removing them from your protocol.

But the behavioral tools, such as NSDR, that are well established to improve baseline levels of dopamine have exceedingly high safety profiles and we know increase dopamine. So a simple way to put this is that, yes, there are a lot of prescription drugs that increase dopamine and epinephrine, and they have some impact on improving working memory drugs that significantly increase dopamine, indeed, improve working memory, provided your baseline levels of dopamine were not already very high.

And, of course, there's that kit of sleep NSDR aka yoga nidra, exercise if it serves you, deliberate cold exposure, essentially zero cost tools that anyone can access and that you have a lot of control over the duration. You have a control over how frequently you do them. And certainly with those very high safety thresholds, very minimal risk to most of those things provided you're safe about your exercise and you're safe about the deliberate cold exposure. You don't do your NSDR in the middle of the road, in the middle of traffic.

Okay, well, then the safety profiles are very high. So I strongly encourage anyone-- in fact, I'll just say I encourage everyone who is interested in improving their working memory, something that certainly I strive to do and that I believe everyone should do at every age-- it's so key for everyday functioning and learning-- that you start with the behavioral tools and then start to explore perhaps the supplementation based and perhaps, perhaps, and if and only if approved by your doctor, the prescription drug tools for improving working memory.

I'd like to take this time to Thank you for joining me for this Ask Me Anything episode. And I'd like to thank you for being a premium subscriber to the Huberman Lab podcast. I'd like to remind you that if I haven't answered your question already, that I will be doing these Ask Me Anythings every month. I will continue to sift through the questions that are on the premium website. And I would encourage you to put additional questions there and to upvote questions that you'd like to see the answers to.

If any of the questions that I responded to today you didn't feel were thoroughly answered enough, then please add a new question there and point that out. I will read all the questions that are there, and I will strive to answer them as thoroughly, concisely, and clearly as possible. Again, you can put those at hubermanlab.com/premium. And as always, thank you for your interest in science.

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