- Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. [upbeat rock music] I'm Andrew Huberman, and I'm a professor of
neurobiology and ophthalmology at Stanford School of Medicine. Today, we are talking all
about food and the brain. We are going to talk about foods that are good for your
brain in terms of focus, in terms of brain health generally, and the longevity of your brain, your ability to maintain cognition and clear thinking over time. We are also going to talk about why and how you prefer
certain foods to others. And I'm going to talk about
the three major signals that combine to drive your food choices. I'll give you a little
hint of what those are. One of those signals comes from your gut and is completely subconscious. This is not the gut microbiome, per se. These are neurons in your gut that are sending signals to your brain that you are unaware of about the nutrient contents of
the foods that you're eating. The second signal is how metabolically
accessible a given food is, meaning how readily that food can be converted into
energy that your brain, not your body, but that your brain can use. And the third signal is perhaps
the most interesting one. It's the signal of belief. It's the signal of what you perceive and believe the food that
you're eating to contain, and what you think it can
do for you health-wise and energy-wise. And that might sound a
little wishy-washy or vague, but we're going to
provide mechanistic data to support the fact that
you can change what you eat so much so that you can drive your brain and your body to crave
foods that are good for you, or at least better for you than the foods you might
currently be eating. This is an incredibly powerful
mechanism that we all have. It's one that I think is
very underappreciated. And today, I'm going to review the data from both animal models, and fortunately, more
recently, human studies, that really do underscore the fact that you can control your
desire for particular foods. Before we dive into today's topic, I just want to briefly touch on some key takeaways from
a previous episode, which is the episode on
time restricted feeding, also called intermittent fasting. The key elements of
time restricted feeding that will benefit your health the most, in terms of weight loss or maintenance, fat loss, organ health,
quality sleep, and cognition, are that the feeding window begin at least one hour after waking. You could push that feeding
window out to begin later, but at least one hour after waking. And that it end at least two, and ideally, three hours
before going to sleep. Some people can end that feeding window much further away from
the beginning of sleep, meaning they're finishing
their last bite of food, for instance, at 6:00 PM, and they're not going
to sleep until midnight. But many people struggle
to get quality sleep if that feeding window is set too early relative to when they go to sleep. So begin the feeding window at
least one hour after waking. End the feeding window at least two hours before going to sleep. And a key feature based on
the scientific research, is that the feeding window itself fall more or less at the same
period of each 24 hour day from day to day. Meaning, if you are going to
eat over an eight hour period, that's your feeding window, you wouldn't want to
start that feeding window at 10:00 AM one day and end it at 6:00 PM, and then the next day, start
at noon and end it at 8:00 PM, and the next day, start it at 2:00 PM and end it at 10:00 PM, and so forth. As much as is reasonably possible, if you want to extract the maximum benefit from time restricted feeding, the idea is to keep
that feeding window at, more or less, the same
phase, as it's called, of each 24 hour day. If it slides around a little
bit for social reasons or whatever reasons, it doesn't seem to be a big deal, but you don't want it sliding around by many hours from day to day, because of the way that
that feeding window impacts other genes called clock genes that regulate a bunch of
other processes in the body. Before we begin, I'd like to emphasize that this podcast is separate from my teaching
and research roles at Stanford. It is, however, part of my desire and effort to bring zero
cost to consumer information about science and science related tools to the general public. In keeping with that theme, I'd like to thank the
sponsors of today's podcast. Our first sponsor is ROKA. ROKA makes eyeglasses
and sunglasses that are of the absolute highest quality. I've spent a career working
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the immune system, and for supporting brain health through the so-called gut brain access. If you'd like to try Athletic Greens, you can go to Athleticgreens.com/Huberman. And if you do that, you
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the five free travel packs, and a year supply of vitamin D3/K2. Today's episode is also
brought to us by Headspace. Headspace is a meditation app backed by 25 peer-reviewed
published studies. I think by now, most people have heard of the benefits of meditation. Reduce stress, improves sleep,
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zero cost resource online. Recently, I took part in an
event called Rethink Education that was put on by Logitech. And there, I gave a 20 minute lecture where I describe the classic and modern neuroplasticity literature in both animal models and humans. The neuro-plasticity
literature is, of course, the literature that describes how to rewire the brain in order to learn. During that 20 minute talk, I describe that literature, but I also spell out what I call the neuroplasticity super protocol, which is nine-plus steps of things that teachers can apply in the classroom to teach any sort of information, music, math, sports, anything, and that students of any kind in any age can use to enhance the
speed and depth of learning. You can find that talk on YouTube by following the link in
the caption to this episode, or by simply going to YouTube and entering the search
terms: Logitech Huberman. Some of the most frequent questions I get are about food and the brain. Everybody seems to want to
know what they should eat and what they shouldn't eat in order to have peak brain function, to be able to focus, and
memorize things, and so forth, and in order to maintain
brain health over time, because nobody wants to lose their memory or have troubles with cognition. Fortunately, there are a lot of data now from really good quality
peer-reviewed studies that indicate certain
things that we can do, including certain foods
that we should eat, and perhaps, even some
foods that we should avoid, in order to enhance our brain function. And, of course, when I say, brain, what I really mean is
nervous system function, because how we are able to move, and remember things, et cetera, doesn't just depend on the neurons, the nerve cells that are in our head, it also depends on our spinal cord, and the neurons that connect
to all the organs of our body. So in general, there are two categories of things that are going to improve brain health from the perspective of nutrition. The first category is the general category of things that we eat and avoid, and things that we do and avoid doing, that will modulate brain
health and function. What do I mean by modulate? Well, getting quality
sleep on a regular basis. Making sure that you're
socially connected. Making sure that you're not depressed. All these things are vitally important to our overall health , and, of course, they will
impact brain function, but they do it, more or
less, indirectly, okay? There are a few things
that happen in sleep which directly benefit brain function, and repair, et cetera. But today, I really want to concentrate, not on the things that
modulate our overall health, but rather, the things that
mediate brain health directly, and in particular, how certain
foods enhance brain function. And we are going to talk about how we can change our
relationship to food. Literally, how we can start
to prefer certain foods that are better for us than others. So just briefly, I want to touch
on the modulatory components, because they are vital. First of all, getting quality sleep on a regular basis and ample sleep on a regular basis is the foundation of all mental
health and physical health. There's no question about that. We've have done several episodes, including the Mastering
Your Sleep episode, which is episode two of
the Huberman Lab Podcast. And we've done a lot of other episodes that are all about sleep, and how to get better at sleeping. So I just want to make crystal clear, that unless you're sleeping
well on a regular basis, your brain will suffer. You won't be able to focus
very well, learn very well, and indeed, there are data linking poor quality sleep to dementia, or at least exacerbating
pre-existing dementias, and things of that sort. So get your sleep in order. The other, of course, is
cardiovascular health and exercise. The general prescription that's
out there in the literature, and I think is well supported, is to get somewhere
between 150 and 180 minutes of cardiovascular exercise per week. If you choose to also use
resistance exercise, that's great. But the 150 to 180
minutes minimum per week of cardiovascular exercise is crucial for heart health, and heart health directly
relates to brain health, because the brain consumes
a lot of oxygen, glucose, and other factors that are
delivered via the blood. So if your arteries are clogged up, and you've got poor
vascular supply to the brain in any region of the brain, your brain will suffer. So get cardiovascular health in order. Now, with those two
modulatory elements set forth, so that we're all aware that they're there and they are vitally important, now, I'd like to turn to the
elements that have been shown to be vitally important
for directly controlling, for mediating neuron function. Neurons, of course, are
nerve cells in the brain, and there are other cell
types, too, of course, that will impact brain function. The most prominent of which
are the so-called glia. Glia means glue. But even though, for a long time, people thought that these cells were just kind of holding
things together passively, the glia play a very active role in the metabolism neurons
in brain function, and probably, also, in cognition, in thinking, and so forth. So what are the things that
directly impact brain health, and what are the foods that we can eat that will support brain health? Generally, when we think
about neuron function and brain function, we default to a discussion about fuel. The fact that neurons use
glucose, which is blood sugar, and that they require a lot of it. In some cases, they'll use ketones, which we will talk about
a little bit later, especially in people that are
following a low carbohydrate or ketogenic diet. But before we can even consider the fuels that neurons use in order to function, we have to talk about the elements that actually
allow those neurons to be there and to stay healthy, what actually makes up those neurons. And that brings us to, what I would argue, is the most important food
element for brain function, and that is fat. And that may come as a surprise, but unless one considers the
water content of the brain, which is very high, a lot of our brain, and a lot of the integrity
of the nerve cells, the so-called neurons in our brain, and the other types of
cells comes from fat. And that's because nerve cells
and other cells in the brain have a external layer. It's what's sometimes called
a double-layered membrane. It's essentially two thin layers that serve as a boundary
between those cells, and that boundary is important, because how things pass
across that boundary actually regulates the
electrical activity of neurons, which is the way that neurons
fire, and communicate, and keep you thinking, and acting, and doing all the good things that those neurons allow us to do. And those membranes are made up of fats, but they're not made up of the fats that are around our belly, around the other organs of our body. They're not made up of storage fat. They are made up of structural fat. And maintaining the so-called integrity of that structural fat, meaning the health of those neurons, is going to come, in large part, from the foods that we eat. Now, this needs to be underscored. What I'm saying is, that
the foods that we eat actually provide the structural
basis, the building blocks, of the very neurons that
allow us to think over time. And as I mentioned earlier, the fat that makes up those
neurons and other nerve cells is different than the other
types of fat in the body. So what type of fat is it, and what should we eat in order to support that
fat and those neurons? And the answer is the so-called essential fatty
acids and phospholipids. Now, those are, more or
less, the same thing, but I just want to make
a very large literature very crystal clear. Essential fatty acids can include the so-called EPA variety or DHA variety. You hear about omega-3s and omega-6s. Most people are getting enough
omega-6s from their diet. Not everybody, but most people
are getting enough omega-6s. However, most people
are not getting enough omega-3s in their diet to
support healthy brain function in the short and long-term. I've talked before about the benefits of elevating the levels of
omega-3s in one's diet for sake of offsetting depression
and for enhancing mood. And indeed, there's a
wealth of literature now pointing to the fact that
ingesting at least one, or two, or even three grams per day of EPA form of essential fatty acid can have effects, positive effects, on mood and wellbeing
that are at least on par with some of the major
antidepressant treatments out there, but without similar side effects to those antidepressant treatments. And that for people that are
already taking antidepressants, that supplementing with one, to two, to three grams of EPA
essential fatty acids can actually allow a lower dose of antidepressant treatment to be used, and still be effective. So that's depression. But just in terms of maintaining
normal cognitive function in people that aren't depressed, the EPAs and omega-3s seem to
play a very important role. Of course, you can supplement EPAs through various fish oils, and it could be liquid fish
oil, or a capsule fish oil. Some people, if they're not
interested in eating fish for whatever reason, they're allergic, or for ethical reasons, they can take krill oil. And if they don't want to use krill oil, they can use algae and other forms of EPA. However, I think it's clear, that one can get a lot of
EPA from the proper foods. And it turns out, that those
foods, not surprisingly, don't just contain high levels of EPA, but they also contain other things that are beneficial for brain health. So what are foods that
are high in omega-3s that we should all probably be consuming, at least on a daily basis? The number one is fish. So things like mackerel,
and salmon, and herring, and oysters, and sardines, and anchovies. And perhaps, the heavyweight champion of EPAs per unit volume is caviar. Now, I don't know about you, but I'm not eating a lot of fish. I'm not eating a lot of caviar. I don't think... I can't remember the
last time I had a caviar, unless it was sprinkled
on a little bit of sushi. I'm not a big fish eater personally. I will from time to time. But that's one reason why one might want to supplement
with EPAs from another source. But also, EPAs are found
in chia seeds, in walnuts, in soybeans, and other plant-based foods. You can look these up online, and you'll immediately see that there are a lot of sources of EPAs. And many of the foods that I listed off might be appetizing to you, some of them might be unappetizing to you, or some of them you might
be sort of neutral about. But it's very clear, that eating foods that
are rich in omega-3s, and/or supplementing with omega-3s, to get above that 1.5 grams, and ideally, up to two,
or even three grams, per day of EPA can be very
beneficial for cognitive function in the short and long-term. Later in the episode, I'm going talk about how to actually change your relationship to particular foods, so that foods that you
don't particularly like, you can actually start to like more, and that might be
important for those of you that are thinking, mackerel, sardines. I'm making this face, 'cause, frankly, those are not
foods that I naturally like. But again, I want to emphasize, that you don't have to consume fish and animal products in order
to get sufficient EPAs. You can get them from plants. But I do believe, based on the quality
peer-reviewed research, that everybody should be striving
to get a minimum threshold of at least a gram and
a half of EPAs per day one way or the other. The great thing about omega-3s is that they are also
thought to be beneficial for things like cardiovascular health. And although there's
some controversy there as to whether or not two
grams, or three grams, or six grams is ideal for
cardiovascular health, I think the bulk of
evidence points to the fact that getting sufficient
omega-3s in the diet is going to support cardiovascular health. Certainly not the only
thing people should be doing to support their cardiovascular health. Aerobic exercise, and so
forth, being important also. But it does seem to support
cardio vascular health, and in doing so, supporting brain health. However, what I'm emphasizing is, ingestion of omega-3s to support the very cells within the brain that make up our cognition, that allow for cognition,
and for movement, and memory, and all the other marvelous
things that the brain does. The other compound that has been shown to be directly supportive
of neuronal function is phosphatidylserine, which is abundant in meats and in fish. So here we are again back to fish being an important source of brain supporting food. Phosphatidylserine is
something that, nowadays, people are supplementing. It's a lipid-like compound that, at least in three studies, have been shown to improve cognition. These weren't huge effects, but they were statistically
significant effects. And as well in more than three, at least five studies, to reduce cognitive decline. And this is interesting. In every case, it was 300 milligrams
supplemented phosphatidylserine, but one, again, doesn't need to supplement
phosphatidylserine. Phosphatidylserine can be
derived, as I mentioned, from meats and fish, and to some extent, from
cabbage of all things. So I don't know how much
cabbage people are ingesting. But later, when we talk about gut health, and the relationship between
gut health and brain health, I'll mention fermented foods. And, of course, one of the most readily available
fermented foods out there that at least many people
find appetizing is sauerkraut, which is, of course, made from cabbage. It's fermented cabbage. So for those of you that
do consume meat and fish, provided you're getting enough fish, you're probably getting
enough phosphatidylserine. For those of you that are interested in supplementing phosphatidylserine
to get these effects that were reported in
these various manuscripts, which, by the way, I've
read, and looked solid. I mean, I don't think we've seen the landmark study showing that supplementing with phosphatidylserine at 300 milligrams per day is going to create a huge offsetting of a massive cognitive decline, or a massive increase in brain function. These seem to be modest effects, but the effects do appear to be real. For those of you that are interested in supplementing with phosphatidylserine, it's a relatively
inexpensive supplement that, again, is lipid-like. So it's mimicking some of the same things that you would get from food, but in a higher concentration. Now, after EPA, fatty acids,
and phosphatidylserine, I would say, third on the list of things that come from food that can readily support brain
function would be choline, and that's because of the
relationship to choline in the biosynthesis pathway
for a acetylcholine. Acetylcholine is a neuromodulator, not a neurotransmitter, but a neuromodulator in the brain. A neuromodulator is a
chemical that modulates the function of many brain circuits, and also, circuits within the body. I'll mention what those are in a moment. But acetylcholine, as a neuromodulator, tends to enhance the activity, the electrical activity
and chemical activity, of certain sets of neurons, and downplay the activity
of other neurons. So it's sort of a conductor of sorts leading to enhanced function and activity in certain
brain areas and circuits, and not in others. For instance, the brain
areas that are involved in focus and alertness. We have multiple clusters
of neurons in our brain that make acetylcholine. Two of the most prominent and well-known are the so-called nucleus basalis, which is a cluster of neurons deep in the basal forebrain that highlight particular
areas of our brain. Highlight meaning when acetylcholine is released from those neurons at their nerve endings in
particular areas of the brain, those particular areas of the brain can undergo enhanced levels of activity relative to surrounding area. So it's kind of a
electrical highlighter pen, if you will, by analogy. That is the basis of much
of what we call focus, or our ability to concentrate on a particular batch of information that's coming in through our
eyes, our ears, our nose, or even things that we're
just thinking in our head. So having ample choline for
production of acetylcholine allows for focus through, of
course, many intervening steps. There are also regions of the brain in the so-called back of
the brain, the hindbrain, that release acetylcholine that are involved in
general states of alertness. And not surprisingly then, many of the treatments
for Alzheimer's disease, which is an inability or challenges with remembering
things and focusing, are drugs that impact the
acetylcholine pathway, and are aimed at enhancing
the amount of acetylcholine that's available to neurons. And it can do that through a
number of different mechanisms. You can do that by enhancing the amount of acetylcholine
that's created, or you can do that by taking a drug that can reduce the amount of enzyme that gobbles up the acetylcholine, and in doing so, leading
to more net acetylcholine. But outside of the scenario where somebody has cognitive
decline due to Alzheimer's, all of us are able to focus
to some degree, or not, or are able to be alert
to some degree, or not, based on the amount of
acetylcholine that we have. Now, other processes,
of course, are involved. But what this means, is that making sure that we have enough of the substrates to create
acetylcholine is vital if we want to be able to focus, and that's why dietary
choline is so vital. And the primary source for
dietary choline would be eggs, and in particular, egg yolks. And this, again, has a very
interesting relationship to our evolution as well. We're always referred
to as hunter gatherers, but when one hears hunters, we often think about
meat and animal sources. And indeed, as a species, we hunted many, many
other species of animals to consume them, and still do. But we also fished. We talked about that earlier. And consumed a lot of fish, and we consumed a lot of eggs. Eggs are an incredibly rich source of nutrients for the brain, and that's because the egg, actually, if you think about it, contains all the nutrients
that are required in order for an organism to grow. You know, a bird that's in a egg shell, it's got the yolk there, and it's using that yolk for a reason. It's using that yolk as a source of fuel. It's using that yolk as a source of, literally, building blocks in order to create its nervous system. Many years ago, I worked on chick embryos, and it was these amazing experiments. You could actually take an egg, and you could create a
little window in the top, and these were fertilized eggs, and you'd see, over time,
you could peer in there, literally look in with a microscope, or even with the naked eye, and you would see this little chick embryo sitting on top of that
yolk growing, and growing, and growing, and growing, and the yolk getting smaller, and smaller. It's really, yeah, incredible. They're using that as a source for all the building blocks of the body, but in particular, the nervous system. So eggs are a rich source of choline. Some people will supplement with choline. However, food sources seem to
be the best source of choline. And as with the EPAs and the omega-3s, there are plenty of foods
that are non-animal-based that contain choline. So if you're somebody
who doesn't eat eggs, or doesn't want to eat eggs, things like potatoes, nuts, and seeds, and grains, and fruit, they don't have as much choline as eggs, but they do contain choline. So you can look up the values of choline that are present in those various foods, and make sure that you're
reaching the threshold amount of choline for you. In general, most people
should probably strive to get somewhere between 500 milligrams and a gram of choline per day. So 1,000 milligrams. And some people rely on supplementation in order to hit those levels, because they're not
eating a lot of egg yolks, or they're not eating
a lot of other foods. Certain fish contain
choline, for instance, and the other foods I
listed off a few minutes ago from plant-based sources. So some people will supplement with 50 to 100 milligrams, or whatever amount is necessary to get them up to that one gram, or even a two gram, dose per day. So we have three things that we know can support nerve cells. EPA, in particular, omega-3 fatty acids, phosphatidylserine, and choline, those three things I would list off as the top three things for enhancing neuron function, and the integrity of neurons
in the short and long-term. And this, again, is setting aside the vitally important factors
of hydration and electrolytes. I've said it before on other podcasts, but if you're not ingesting enough water, and you're not getting enough sodium, and magnesium, and potassium, then, obviously, your neurons can't run, because a lot of the brain is water. You need to maintain proper hydration. And sodium, potassium, and
magnesium are important in order for nerve cells to function. In fact, they are actually
the components, the ions, that pass across those lipid membranes, those little fatty membranes that we were talking about earlier, that allow the neurons to
generate electrical activity and communicate with one another. So definitely, you want to hydrate enough. We will do an entire other episode all about hydration and electrolytes. But omega-3s, the EPAs,
phosphatidylserine, and choline, it's obvious are going to
improve brain function. How much they will improve brain function probably depends on how well your brain
was working previously. In fact, many of the studies that have looked at the
effectiveness of these compounds have looked in people that
are suffering from mild or even severe cognitive decline. And while the outcomes
of those studies vary, given the interest in
maintaining brain function, given the fact that we
don't make new neurons throughout our entire life, and given that everybody has to eat, these are quality healthy foods that we should all be ingesting anyways. And it's clear that they
can support brain function to some degree or another. Many people will ask what I do
in light of this information. And while I can only talk
about what works for me, I choose to ingest fish
oil mainly in liquid form, because that turns out
to be the easiest way and the most economically affordable way to do it for most people. So there are various forms
of liquid fish oil out there. Some of them include some lemon flavoring, so it doesn't taste like fish oil, because frankly, fish oil, to me, is sort of noxious tasting. And I'll take a tablespoon
of that, or two, per day. If I'm traveling, I'll
use the capsule form in order to hit that threshold. For me, about two, sometimes even three, grams per day of EPA. So not just two or three
grams per day of fish oil, but two or three grams per day of EPA. Now, if I'm eating fish, which as I mentioned
earlier, is not often, then I might reduce the amount
of fish oil that I take. But that's my major source of fish oil. Currently, I do not supplement
with phosphatidylserine. A number of people that I know and trust, and indeed, several colleagues of mine, do take phosphatidylserine. I don't have any good explanation for why I don't take it yet, but I have not tried
supplementing with it yet. Maybe if some of you have, you can place your experience
in the comment section. It would be of interest. And then in terms of choline, in order to get choline in my diet, I do pay attention to the various foods that contain choline, and I try and get those foods
on a semi-regular basis. I do supplement with
something called alpha-GPC, which is, essentially, in
the acetylcholine pathway, or biosynthesis pathway. I don't take it very often, but I will take 300 milligrams of alpha-GPC from time to time. From time to time, I mean anywhere from two
to three times per week. I'll generally do it early in the day, 'cause it, for me, can have a little bit
of a stimulant effect. Although, it's not nearly
as stimulating, say, as a double espresso, or triple espresso. But that's one way in which I
enhance my choline function. And some people choose to
get it from supplementation, because it's straightforward. There are a lot of supplements out there that contain alpha-GPC. Some people are taking dosages as high as 900 milligrams per day. That sounds very high to me. The studies of offsetting
cognitive decline using alpha-GPC did use quite high dosages of 600 to 900, or even 1200, milligrams per day. So it has been used at those
much higher concentrations. But because, fortunately, at least, not yet, or not to my awareness, I'm not suffering from
any cognitive decline, I will supplement with 300
milligrams every now and again. Next on my list of compounds that have been shown in
peer-reviewed research to improve neuronal and
brain function is creatine. Creatine can be derived from meat sources. It can also be supplemented. Some of you are probably
familiar with creatine or have heard about creatine from the context of the
health and fitness world, where creatine is used to
bring more water into muscles, which can enhance the
strength of those muscles, as well as bring water into other tissues. It doesn't just draw
more water into muscle, it can draw more water
into the body generally. Creatine has also been shown to have an important role in brain function. And once again, this is
something that came up during the discussion about
depression a few episodes back. Creatine can actually be used
as a fuel source in the brain. And there's some evidence that it can enhance the function of certain frontal cortical
circuits that feed down onto, or rather, connect to, areas of the brain that are involved in mood
regulation and motivation. And that's where creatine
plays a role in depression, or rather, where creatine supplementation seems to be able to assist in
some forms of mild depression. That's an emerging literature. It's still not well-established. However, there is now ample evidence that creatine supplementation
can enhance brain function in certain contexts. And if you're interested in learning more about
what those contexts are, there's an excellent
review that just came out. The first author is
Roschel, R-O-S-C-H-E-L. We will provide a link to this study, rather, this review,
excuse me, in the caption. This was published just
very recently in 2021. And one thing to make clear, is that creatine supplementation has been shown to be especially useful for people that are not consuming any meat or other sources of foods
that are rich in creatine. What is the threshold level
of creatine to supplement in order to get the cognitive benefit? It appears to be at
least five grams per day. Now, the most typical form of creatine is so-called creatine monohydrate. There are other forms of creatine as well, some of which are thought to not draw as much water into non-muscle tissues, and for some people,
that's attractive to them. They don't want water sitting
below their skin, et cetera. I should emphasize, that the responses to creatine
in that sense can differ. Some people get a little
bit of water retention. Some people experience more. There's some evidence
that creatine can impact some of the hormonal pathways, that it might enhance levels of so-called dihydrotestosterone, DHT, and therefore, because DHT
is involved in hair loss, there are these theories that
creatine can cause hair loss. And indeed, for people that are very DHT sensitive, it might. There's going to be a lot of
variation person to person in terms of how much creatine impacts DHT, and how many DHT receptors
they have on their scalp, and therefore, whether or not
they experience hair loss. I'm just giving you all this information, so that you're aware of the various things that creatine can do. But nonetheless, I think it's interesting that creatine supplementation
of five grams per day, that's creatine monohydrate, has been shown to improve cognition in people that aren't getting
creatine from animal sources. And there's some evidence
detailed within the review that I just described, that creatine supplementation
can also enhance cognition in people that are also
eating animal products. So I personally take
creatine five grams per day, and have for a very long time. I can't say that I've
noticed a tremendous benefit, because I've actually
never really come off it, and so I've never done
the control experiment. I take it more as kind of a
baseline insurance policy. For me, I'm probably losing, I'm certainly losing some of my hair. Whether or not that's
due to creatine or not, I've never done the analysis. But what I can say is that, I generally consume these things like EPAs, creatine, alpha-GPC to set a general context
of support for my neurons, for my brain. And, of course, I also pay attention to the foods that contain
these various compounds. So I don't actively eat additional meat just to obtain creatine. I eat a fairly limited amount of meat. I don't restrict it, and I do eat meat, but I don't actively seek
out creatine in my diet. Rather, I use supplementation in order to hit that five
grams per day threshold. Next on the list of foods that are beneficial for brain health is one that you've probably
seen pictures of online, because there seems to be a practice of putting pictures of blueberries and other dark berries next
to any title that says, "Foods that benefit your brain". There are a lot of foods out there that have been purported
to improve brain function. The interesting thing about
blueberries and other berries, blackberries, dark currants, any of these thin-skinned berries that are purpleish in color, is that they contain what
are called anthocyanins. Anthocyanins actually
have some really nice data to support the fact that
they improve brain function. Now, whether or not it is
direct effects on neurons, or whether or not it is
by lowering inflammation, or some other modulatory
effect, isn't quite clear. But I think by now, there's
enough data to support the fact that eating a cup or two of
blueberries pretty often, every day, or maybe you have blackberries, or maybe it's black currants, that these anthocyanins are good for us, that they are enhancing
our overall wellbeing at a number of different levels. And just to give you a couple examples of where there are actually
peer-reviewed studies to support those statements, the anthocyanins of which blueberries and other dark berries are rich in have been shown to reduce
the amount of DNA damage, has been shown to reduce significantly, although, albeit, slightly,
excuse me, cognitive decline. And that particular study was supplementation of a blueberry extract. I'll talk about the
difference between extract and actual blueberries in a moment. But supplementation of blueberry extract in offsetting cognitive
decline in elderly people. So what constitutes elderly is always a little bit of
a debate and a discussion. But in this case, what they did, is they supplemented with
somewhere between 428, I don't know why they selected 428, and 598 milligrams of
anthocyanins daily for 12 weeks was associated with improvements on verbal learning and memory. And they had some other beneficial changes that were within the bodily organs, and blood glucose
regulation, and so forth. Positive changes. But that's one study. In this case, elderly meant 65 or older. That study, and a number
of studies like it, looking at things like
mildly enhanced memory, reduced insulin levels,
reduced oxidation of LDL, these sorts of things, have basically created a situation where anytime you Google or look up foods that
enhance brain function, you're going to see a
picture of a blueberry or some other berry, because of these anthocyanins. I personally don't
supplement anthocyanins. I do like blueberries. I eat blueberries when they're in season. I love them. I'm what you would call a
drive-by blueberry eater. Like if there are blueberries
in a bowl on a table, and I'm walking by, I just have to scoop them up, like some sort of bear, or other animal, and pop them in my mouth. So blueberries don't last long around me. One of the issues with berries, like blueberries, and
blackberries, and so forth, is that quality sources of
them can be pretty expensive. And then, of course, when
they're not in season, they're hard to get, and so that's why some people
will supplement with them. So that range of about 400 to
about 600 milligrams per day seems to be the minimum threshold for getting a cognitive effect
in these elderly patients. In that case, they were patients. A good review about the anthocyanins potentially contributing to
offsetting cognitive decline in things like Alzheimer's, and also enhancing brain function in people that don't have Alzheimer's, is a review by Afzal, A-F-Z-A-L, that was published in 2019. We will also provide a link
to that study in the caption. When one looks across the
total batch of studies that are out there on this, it appears, that if one
is going to supplement with blueberry extract to get the anthocyanin effect on cognition, dosages of somewhere between
5 1/2 or about 11 grams seem optimal with the higher end, closer to 10 or 11 grams
being more beneficial. The blueberry eaters out there like me, who prefer to get their anthocyanins from the actual berries, it appears that somewhere
between 60 to 120 grams of fresh blueberries each day is the way that you can
get sufficient anthocyanins to at least shift your system, or bias your brain towards these
enhanced cognitive effects. So we've got EPA fatty acids, we've got phosphatidylserine, we've got choline, we've got creatine, and
we have the anthocyanins. And the last item that I'd
like to place in this list of food-derived things that can enhance brain
function is glutamine. Glutamine is a very
interesting amino acid. I've talked about
glutamine on here before. There's some evidence,
although, somewhat scant, there's some evidence that glutamine can enhance immune system function. So people will supplement with glutamine, or people can get glutamine from foods. Foods that contain a lot of glutamine are things like cottage cheese. There are also other sources of glutamine. Glutamine is rich in protein rich foods, things like beef, chicken,
fish, dairy products, eggs. But also, for you non-animal food consuming people out there, vegetables, including
beans, cabbage, once again, spinach, parsley, things of that sort. So those foods contain glutamine. For people that supplement with glutamine, generally, they will take
anywhere from a gram, as much as 10 grams, per day. Why would they want to do that? Well, there's also some
evidence starting to emerge that glutamine can help
offset sugar cravings, and I've talked about this
on the podcast before. We're going to talk more about the basis for this a little bit later. But in brief, we all
have neurons in our gut that sense the amino acid
content, the fat content, and the sugar content of
the foods that we eat, and signal in a subconscious
way to our brain whether or not the
foods that we are eating contain certain levels
of certain amino acids. And so we actually have
glutamine-sensing neurons in our gut that actually have their little processes, their little axons and
dendrites, as we call them, in the mucosal lining of the gut. They're not just sensing glutamine, but when they do sense glutamine, they respond, and they
send signals to the brain that are signals of
satiation, of satisfaction. And in doing so, can offset
some of the sugar cravings that many people suffer from. Now, here, we're talking about glutamine for sake of enhancing cognitive function. And this is interesting, because it's been shown that
glutamine supplementation can offset some of the
negative effects on cognition caused by altitude and oxygen
deprivation of other sorts. Yeah, okay, well, that's kind of a strange and unique situation. If you're going up to altitude, should you supplement with glutamine in order to be able to think more clearly? Well, it appears that there's
good rationale for doing that. But the reason I bring this up, assuming that most people, including me, are not going up to high
altitudes very often, is that it's been
well-established that apnea, failure to breathe properly during sleep, can contribute to age-related, and even non-age-related,
cognitive decline. There are a lot of reasons for apneas, ranging from obesity to
obstruction of the airways, for other reasons. There are tremendous number
of underlying causes of apnea, and it's something to be taken seriously. I mean, heart attacks, all
sorts of metabolic issues, are caused by apnea. Apnea is a serious issue that
disrupts the depth of sleep, and it's a serious
health issue in general. In any event, apnea is associated with cognitive decline and cognitive dysfunction,
even in young people, and it does appear that
glutamine supplementation can offset some of the cognitive deficits that are associated with reduced
oxygenation of the brain. If you'd like to learn more about how apnea can negatively impact cognition, there's an excellent paper that was published on this in 2018. The first author is Sharma, S-H-A-R-M-A. It should be easy to find. The title of the paper is "Obstructive Sleep Apnea
Severity Affects Amyloid Burden In Cognitively Normal Elderly". This was a longitudinal study. Amyloid burden is a
correlate of Alzheimer's and other forms of neurodegeneration and cognitive decline
associated with memory deficits. So obstructive sleep apnea
[clears throat], excuse me, is a very serious issue for which glutamine appears to be able to offset some of the
negative symptomatology. So how is it that glutamine, either from food or
through supplementation, can offset some of these so-called hypoxic effects
caused by sleep apnea? Hypoxia being a lack
of oxygen for the brain that relate to cognitive decline. It appears to have this positive impact by way of reducing inflammation. So if you want to look
more deeply into the various biological pathways and the supplementation regimes for this, the paper that I think is
really spectacular is a paper, last author is Quaresma, Q-U-A-R-E-S-M-A. That's Q-U-A-R-E-S-M-A. It's a review. "The Possible Importance of Glutamine Supplementation to Mood and Cognition in Hypoxia
from High Altitude". And even though paper is about high altitude-induced hypoxia, it does seem to have direct relevance to the sorts of apnea that
are related to Alzheimer's and other forms of cognitive decline. Now, I've been taking
glutamine as a supplement, gosh, since I was in college, mostly because I felt, either
by superstition or by reality, that it protected me from
various flus and colds, and things of that sort, because of the purported
immune-enhancing effects. Again, those immune-enhancing effects have some data to support them, not a ton. However, I got into the
habit of taking glutamine, and now that I've learned that glutamine seems to also have some cognitive-enhancing effects, possibly, it's a supplement that I continue to take. I take very small amounts of it, but I do take it on a regular basis. So that, more or less, completes
the list of things that, at least by my read of the literature, are things that are
supported by at least three, and in some cases, as many
as hundreds of studies, in various populations, that have been explored
in mouse studies often, but also in a number of human studies. I want to emphasize again, that all of the things I listed out, whether or not it's EPAs, whether or not it's phosphatidylserine, whether or not it's choline, whether or not it's the various compounds that are in berries, et cetera, all of those can be extracted from food. There is not any law that says that you have to get them
from supplementation. Supplementation can help you get to the very high levels of those things, if you want to work on the higher end, if that's right for you. Obviously, check with your
doctor before taking anything or removing anything from your
diet or supplement regime. But in general, you can get
these things from foods. It's just so happens, that
for some of these compounds, the foods that they're
contained in, like fish, are not foods that I particularly enjoy, and so I rely on [clears
throat], excuse me, I rely on supplements in order to get sufficient levels for me. But again, you can get
these levels from food. And the reason I made this list, the reason that I emphasize these things in this particular order, is that they support the
structure of neurons. They support the structure of
the other cells of the brain that make up our cognition and that are important for our focus, and our ability to remember
things, and so forth. And they are less so in the category of so-called modulatory effects. They will also have
modulatory effects on sleep, on inflammation, or reducing inflammation
throughout the body, on cardiovascular function, all of which I believe
are positive affects. At least what the literature tells us, is that none of these compounds are harming other systems of the body, provided they are taken
at reasonable levels. But everything in this
list is directed towards answering the question, what can I eat, what can I ingest by way of
food, and/or food supplement, that can support brain
function in the short-term and in the long-term? So I hope you find that
list beneficial for you. If not for use, at
least for consideration. So now, having talked
about some of the foods and micronutrients that are
beneficial to our immediate and long-term brain health, I'd like to shift gears somewhat, and talk about why it is that we like the foods that we like. We've all heard before that we are hardwired to pursue sugar, and to like fatty foods, and that calorie-rich
foods are attractive to us for all sorts of reasons, you know, surviving famines,
and things of that sort. And while that is true, the actual mechanisms that underlie food seeking and food preference are far more interesting than that. There are basically three channels in our body and nervous system by which we decide what foods to pursue, how much to eat, and
whether or not we will find a particular food attractive, whether or not we will
want to consume more of it, whether or not we want to avoid it, or whether or not it's just sort of so-so, what I refer to as the
yum, yuck, or meh analysis. And indeed, that's what
our nervous system is doing with respect to food. It's trying to figure out whether or not, yum, I want more of this, yuck, I want to avoid this, or meh, it's so-so. Now, while that may seem like a overly simplified
version of food seeking and food preference, it's actually not that far from the truth. It actually correctly captures much of the biology of food preference. So let's talk about what
these three channels for food preference are. The first one is an obvious one. It's taste on the mouth. It is the sensation that we
have of the foods that we eat while we're chewing them, and those sensations, which are literally just
somatosensory, touch sensations, you know, the palatability of food as it relates to the consistency
of food, that's important. And as you've all heard before, we have sensors on our tongue and elsewhere in our mouth that detect the various
chemicals contained within food, and lead to the senses of taste, which we call bitter, sweet,
umami, salty, and sour. Now, most of us are familiar
with the sense of bitterness that comes from something
like a raw radish, sweet, which comes, obviously, from sugars of different kinds, fructose, glucose, et cetera, salty, salty, and sour, think lemon or
lemon juice, for instance. And then I mentioned umami. The umami receptor is a
receptor that responds to the savory taste of things. So that's what you might find in a really wonderfully rich tomato sauce. For those of you that
eat meat, and like meat, a really well cooked ,not
necessarily well done, but properly cooked, I should say, steak, if that's your thing. And umami is present in
both plant and animal foods, and gives us that sensation of savoriness. It almost has a kind of little
bit of a briny taste to it, or braised taste to it. And indeed, brazing of meats
and brazing of vegetables is done specifically to
activate that umami receptor. So we have those five basic tastes. Those are chemical sensors
on the tongue that, what we call, transduce those chemicals. Those chemicals, literally, in
food bind to those receptors, and it is transduced, meaning the binding of those
chemicals to the receptors is converted into an electrical signal that travels in from the tongue along what's called the gustatory nerve. The gustatory nerve then synapses, meaning it makes
connections in our brainstem in the so-called nucleus
of the solitary tract. There are other nuclei back there. Nuclei just aggregates of neurons. And then it sends information up to the so-called insular
cortex, to the insula. I want to highlight the
insula this episode, because we are going
to return to the insula again and again in this
episode, and later. The insular cortex is
a incredible structure that we all have that mainly is concerned
with so-called interoception, or our perception of what's
going on inside our body. So it could be the amount
of pressure in our gut because of how much food we've eaten. It could be the acidity of our gut, if we're having a little bit
of indigestion, for instance. It can also be the case, that neurons within the
insula are paying attention to how stressed you are,
or how alert you are, or how tired you are. So it's really an inward
focusing structure. It focuses on how we feel internally. And not surprisingly, the taste system sends information
up to the insular cortex to give us a sense, literally,
of what we've ingested, whether or not what we're
tasting tastes good or not. We will return to insular
cortex in a few moments. A very important thing to understand, is that the neurons in
the areas of the cortex, your cortex and mine, that
respond to particular tastes are providing an internal representation of an external sense. What do I mean by that? I don't want to be at all abstract. We take these foods, we break them down in our
mouth by chewing them, or sucking on them, whatever it is the food happens to be, those chemicals bind to those receptors, and electrical signals
are sent into the brain, but they are just electrical signals, just like notes being played
on the keys of a piano. There's no unique signature
for salty or sweet. It is the relative activation
of one set of neurons that was activated by sweet, or another set of neurons
that was activated by umami. It's that relative activation traveling into the brain in,
essentially, the same form, the same electrical signals. This is really incredible, right? Electrical signals are
sent into the brain, and you say, aha, that's
sweet and I want more of it, or that's bitter, or I want less of it, or that's umami flavored, and I really, really like that, really like savory foods, as I happen to. That should immediately
strike you as incredible, because it means that your representation of what you want more of or
less of is electrical in nature. And to really tamp this issue down, studies that were done by
Charles Zuker, Z-U-K-E-R... He's a absolutely
phenomenal neuroscientist at Columbia University in New York. Studies done by the Zuker
Lab have shown that, first of all, they could identify
the neurons in the cortex deep in the brain that
respond to a sweet taste or to a bitter taste. It turns out, they are non-overlapping populations of neurons. And then using some molecular tricks, they were able to either silence or activate the neurons
that, for instance, respond to sweet. When they do this, they see incredible
consequences on perception that, indeed, occur in your brain, and my brain as well, all the time without these kind of manipulations. Here's the experiment. They have a subject drink
water that contains sugar, or drink water that
contains a salty substance, or drink water that contains a bitter substance, for instance. Okay, I'm sort of paraphrasing
a large amount of work. They identify the neurons
that respond to sweet tastes. They see, as many researchers have seen, that subjects prefer sweet
taste to other tastes, and certainly, sweet tastes to bitter, or sweet tastes to
nothing, so to plain water. And then they go in, and they are able to
selectively silence the neurons that represent sweet. And when they do that, they eliminate the preference
for that sweet taste. Now, that might seem obvious, the neurons respond to sweet, and you silence those neurons, they no longer seek out sweet. But that should strike
you, also, as incredible, because they're not actually changing what's happening on the tongue or in the deeper layers of the brain. Conversely, they can have
subjects drink bitter water or plain water while activating, selectively activating, the
neurons that respond to sweet. And what they find, is that then subjects will
actively prefer bitter or plain water to actual
preferences, such as sweet. So what this means is that, your perception of what
you like is a central, meaning deep within the brain, phenomenon. It's not about how things
taste on your mouth. Now, of course, under normal conditions, where there aren't these experimental manipulations being done, those things are positively correlated. Sweet tastes trigger the activation of sweet neurons, for instance. Neurons in the mouth
that respond to umami, trigger the activation
of neurons in the brain that respond to umami, and so forth. So they're correlated in a way that makes you seek out
the things that you like, and avoid the things that you don't like. But as we'll see in a few minutes, turns out, that that is
not a direct relationship that is hardwired. You can actually uncouple the preference for a particular taste with the reward systems in the brain in a way that, for instance, would allow you to eat, or I should use myself as an example, 'cause I don't particularly like fish. I've had a few meals that include a fish that were pretty good, but none of them were memorable in the kind of positive way, that like some other events
in my life were memorable. But by way of these circuitries, and the way they link up with one another, it's actually possible to
rewire one's sense of taste and preference for particular foods. If this is seeming at all vague to you, just hang in with me a little bit longer, because I will provide you
with the information, tools, and resources with which
to navigate this process. But the most important
thing to understand is that, like with our hearing, like with vision, like with smell, taste is an internal representation that has particular goals for you. Your sense of what tastes good is related to particular things that are occurring in your brain and body, and that are likely to give your brain and body the things that it needs. It is not simply a matter of what you, quote/unquote, "like", or what tastes good, or
what doesn't taste good. Let me give you a
relatively simple example of how your body and your brain are acting in a coordinated way to make you prefer certain foods, and indeed, to pursue certain foods more. As I just mentioned, you
have neurons on your tongue that respond to different tastes. But, of course, your digestive
tract isn't just your tongue, it's also your throat. It goes all the way down to your stomach, and, of course, your intestines. It's a long tube of digestion. All along that tube there are neurons. Some of the neurons are responding to the mechanical size of whatever portion of the
digestive tract it happens to be. So for instance, how distended,
or empty, or full, rather, it doesn't have to be distended, it depends on how much you ate, but how full or empty
your gut happens to be, whether or not something you
just ate is temperature hot, you know, is hot in the
sense of hot to the touch, or whether or not it's spicy hot, whether or not it's soothing, whether or not it's
kind of hard to swallow, this kind of thing. So you have neurons all along your gut that are responding to the mechanics related to food and digestion, and that are related to the
chemistry of food and digestion. There's a population of neurons, nerve cells in your gut, that are exquisitely
tuned to the chemistry of whatever it is in your gut. And these are neurons
called neuropod cells. They were discovered many, many years ago, but really defined with and classified with modern tools by Diego Bohorquez. I hope I'm pronouncing
your name correctly. Diego, we've spoken many times, but I can't ever seem to quite capture the proper pronunciation just right. But Diego Bohorquez at Duke University, who discovered that these cells reside within the gut, and place little processes, they're little axons and dendrites, within the mucosal lining of the gut. And there, they are paying attention to, meaning they respond to, amino acids, sugars, and fatty acids. So as your food is digested, as food lands within your gut, neurons there are sensing what
types of foods are available, and what types of things
are making their way through the gut environment. Now, those neurons aren't
actually taking those foods and doing much with them. What they're doing, is they're essentially surveying what qualities
of food are there. And these particular neurons that Diego and his group discovered, send electrical signals up into the brain through a little passage that
we call the nodose ganglion. The nodose ganglion is
a cluster of neurons that then send up their
own process into the brain, and trigger the release of dopamine, which is a molecule that
inspires motivation, reward, and more seeking for whatever
it is led to their activation. These are super interesting neurons, because what they're essentially doing, is they are providing
a subconscious signal about the quality of the
food that you're eating, what it contains, and then triggering the release of a molecule within your brain, dopamine, that leads you to go
seek more of those foods. Now, this has profound
impact on a number of things. First of all, there's the consideration
of so-called hidden sugars. Dr. Robert Lustig, who's a
pediatric endocrinologist at University of
California, San Francisco, has been among the most
prominent researchers to talk about the fact that there are these so-called
hidden sugars in foods. Now, these are not just sugars, that they sneak in just to be sneaky, these are sugars that
are literally snuck in in a way that you can't taste them. That's why they're called hidden sugars. It's not that they just
put them in there for fun. These are sugars that are
placed into processed foods that are designed to trigger activation of these mechanisms to lead you to want to
eat more of these foods, but not because they necessarily
taste sweet or delicious, but because they are activating these subconscious mechanisms that are driving you to
pursue more of these foods. It sounds like a very diabolical strategy, and indeed, it is somewhat
of a diabolical strategy. However, these neurons are also involved in signaling to your
brain when, for instance, you are eating a food that is
rich in omega-3 fatty acids, the fatty acids that we
were talking about earlier. So why is it that you don't crave salmon? Why is it that I don't sit around daydreaming about mackerel? Well, because there's also the influence of the actual taste on the mouth. Under normal conditions, it's a combination of the taste
of the thing on the mouth, plus the subconscious
signaling from the gut. And while this isn't a
discussion about gut microbiome, I should just mention,
that it's very clear that having a healthy gut microbiome allows these neurons to function in a way that serves our seeking of
healthy foods in positive ways. And without getting into a
lot of detail about this, the best way to ensure
a healthy gut microbiome that I am aware of is not necessarily to take supplemental
prebiotics or probiotics. There are actually some reasons why you might not want to do that. But rather, to ingest two to four servings of fermented foods that
are low in sugar each day. There is a recent study published in Cell showing that the ingestion
of fermented foods, two to four servings each day, can enhance the quality of
the mucosal lining of the gut that allows certain gut
microbiota to flourish, and the gut microbiota
that are not good for us to not flourish, 'cause that's the environment
that they settle down into. This is work that was carried out by my colleagues, Justin Sonnenburg, which is in the laboratory
upstairs from me, as well as Chris Gardner,
and others at Stanford. They are certainly not the only
researchers exploring this. But it does appear, that two to four servings of fermented foods each day, so these would be things
like natto, sauerkraut, low sugar fermented foods, is
great for the gut microbiome. And separate studies, not their study, but separate studies have shown that the correct gut microbiome conditions allow these neurons
that signal to the brain to signal the right, at the right times, and in the right ways to
promote healthy food seeking. Many people opt to supplement
with capsule form probiotics. There are some data that suggests that maybe those don't
contain the correct prebiotics and probiotics for setting the correct gut microbiota conditions. That's a little bit of
a controversial issue. Nonetheless, getting
probiotics from fermented foods is probably the simplest and
most straightforward way. It's also the way that we
evolved to do that over many, at least hundreds, and
probably, thousands, or even tens or hundreds
of thousands of years, people have been
ingesting fermented foods, not just for their tastes, but for their health benefits as well. So now I've mentioned two
of the three mechanisms by which we prefer certain foods. One is from the actual taste
that we're familiar with, the taste on our tongue, and in our mouth, in the sensations that make
us go mmm, or ugh, or eh, the yum, yuk, meh responses,
as I referred to them earlier. And then there's this
subconscious signaling coming from the gut that's really based on the
nutrient content of the foods. There's a third pathway, which is the learned association
of a particular taste with the particular quality
or value that a food has. And this is where things
get really interesting, and where there's
actually a leverage point for you to rewire what it is that you find tasty, and that you want to seek more of. The work I'd like to talk about next has been carried out in mouse models, and has been carried out in
parallel experiments in humans. This is largely, not exclusively, but largely the work of Ivan
de Araujo and Dana Small. Ivan de Araujo is at Mount
Sinai School of Medicine. And Dana Small is at Yale. And they, and others in their field, have done incredible experiments exploring how taste and food value, the nutritional value of food, and the impact of that food
on metabolism in the brain drives our food choices, and allows us to change our
food choices for the better. Their groups have done
some really amazing studies involving ingestion of
a particular substance that either contains sugar, and thereby, can elevate
glucose, blood sugar, or not. And varying, meaning
changing the taste associated with that ingestion of sugar. So let me just give you a simple example where they have subjects, these could be mice or
these could be humans, 'cause they've done both sets of studies, drink sweet water as an alternative or a choice to non-sweetened
water, or bitter water, or some other flavor. And what they find, is that
mice and humans will prefer to consume the sweet beverage. Now, it's not always sweet water. Mice like sweet water, but humans will prefer,
for instance, a milkshake, a fatty sweet drink. They'll consume more of that, and not surprisingly, dopamine levels in the brain
increase in response to that. So the taste and the nutrient content of what it is that they're
ingesting are aligned. They are matched. They've also done experiments
where they have no taste, but subjects are being infused with sugar directly into the gut. And not surprisingly, based on everything I've
told you up until now, subjects will pursue more of that thing relative to some other taste, either neutral or negative taste, because that sugar in the gut is triggering the activation of the neurons I mentioned earlier, which is signaling to the brain to pursue more of that thing. So this tells us something important. It tells us that we are driven, meaning we have mechanisms in our brain that make us motivated to pursue more of what brings both
a taste of sweetness, but also that brings actual changes in blood glucose levels up, okay? So we are motivated to eat sweet things not just because they taste good, but because they change
our blood sugar level. They increase our blood sugar level. This is important, because it needn't be the case. It could have been that we were just wired to pursue things that taste good. But what this tells us, is that we are actually
wired to pursue things that increase our blood glucose, so much so that when the small lab... It's not a small lab. It's actually a big lab. But when Dana Small's lab,
and/or Ivan de Araujo's lab, have done experiments where they use a compound
called 2-deoxyglucose, this is a compound that can prevent glucose from
being metabolized by neurons. So blood glucose is going up, but neurons can't use it. What they find, is that the reinforcing or the rewarding properties of a food or taste are eliminated. Put simply, it is not
sufficient for a food to taste good consciously. It is not sufficient for a
food to increase blood sugar. You need blood sugar to go up, and that blood sugar glucose has to be utilized by the neurons, even if it's not associated
with a good taste. And to make it even simpler, if this isn't sinking in, this should make it very clear. What your brain, meaning, what you are seeking
when you eat, is not taste, is not dopamine, is not even a rise in blood glucose. What you're seeking, even
though you don't realize it, because it's subconscious, is you are seeking things
that allow your neurons to be metabolically active. And this is fundamentally important for understanding why you eat, why you eat particular foods, and how you can change your
relationship to those foods. Now, earlier, I referred to circuits that are wired for a particular outcome. And in biology, and in
particular, neuroscience, we refer to things that
are either hard-wired, meaning immutable, and
unchangeable, or soft-wired. A good example of soft-wiring would be the areas of your brain that
are responsible for speech and language are always, more or less, in the same place in your brain
and everyone else's brain. However, they are not
hard-wired to speak French, or to speak English, or to speak Chinese, or to speak German, because depending on where you were born, and the parents that you're born to, you need to be able to speak one or maybe even more languages. The taste system, and this general system of
seeking particular foods, similarly is hard-wired to obtain certain types of nutrients. It tends to like sweet things. Most children naturally like sweet things, some more than others. But naturally, most people
from childhood onward don't particularly crave
very bitter substances. Maybe mildly bitter, but not very bitter. So there's some hard-wiring of preference, but there's also some
soft-wiring in the system that allows it to change. The groups I mentioned earlier have done some really
beautiful experiments looking at how artificial sweeteners interact with the actual
sweet sensing system. And this gets right down
to a number of issues. First of all, it gets to the issue of how we can rewire our taste system in ways that serve us
for better or for worse. Second of all, it gets
right down to the issue of whether or not artificial sweeteners are good for us or bad for us. And indeed, as of just this last year, we know an answer to that question, and turns out, it depends. And I will tell you in a few minutes when it is okay to ingest
artificial sweeteners, and when it is very detrimental to ingest artificial
sweeteners of any kind. Regardless, I'm not going
to name off brand names, but there are different forms of these artificial sweeteners nowadays. And there are various forms of non-caloric plant-based sweeteners for which the same information that I'm about to tell you applies. Okay. So the experiments that were done beautifully illustrate that
you seek out particular foods because of the way they taste, because of their impact
on blood glucose levels, but also on their impact
on the dopamine system, even if your blood glucose
levels don't change. So here's the experiment. One group of subjects
is given a sweet taste of a substance that also raises blood glucose levels, blood sugar, and dopamine goes up, not surprisingly. The second condition, separate subjects consume
an artificial sweetener or a non-caloric sweetener. It is not preferred much
over other substances, but it is sweet, so
it's preferred somewhat. And it does not cause an
increase in blood glucose levels, and not surprisingly,
dopamine levels don't go up. So initially, we don't tend to like artificial sweeteners that much. That's the simple way of putting it. However, if subjects continue to ingest artificial sweeteners, even though there's no increase
in blood glucose level, and therefore, no increase
in brain metabolism, dopamine levels eventually start to rise. And when those dopamine levels
eventually start to rise, you've essentially conditioned or reinforced that artificial
or non-caloric sweetener, and then subjects start
to consume more of it, and they actually get a
dopamine increase from it. So that's interesting. It says that, consuming more
of these artificial sweeteners, or consuming them for a
longer period of time, can start to tap into the dopamine system, and lead us to seek out or consume more of these
artificial sweeteners. Many people are probably
familiar with this, because we tend to, or I should say, people report, that when they ingest these
artificial sweeteners, at first, they don't taste very good, but then, over time, they
seem kind of tolerable, and then maybe even pleasureful, and then some people feel, quote/unquote, "addicted" to various diet
sodas, and things of that sort. Now, there's another condition
that's been explored, and that's the really
interesting condition, and it's the condition where
an artificial sweetener is paired with a substance
that can increase blood sugar, but not because it tastes sugary, like a normal sweet substance. So now, there's an artificial sweetener that's coupled with an actual
increase in blood glucose. The natural world scenario
where this would happen would be drinking a diet soda
which contains no calories, and therefore, would not
increase blood glucose, but is sweet, with a food
that increases blood glucose. And when that happens, what you're essentially doing, is tapping into the dopamine system. This non-caloric sweet
taste is paired with it, and there's an increase
in neuron metabolism. So you have all of the
components for reinforcement. And as a consequence, you get in a sort of
Pavlovian conditioning way, a situation where, later, when you ingest that artificial sweetener, you actually get not only
the increase in dopamine, but you get alterations
in blood sugar management. Now, blood sugar cannot go up if you don't ingest something
that makes blood sugar go up. So it's not as if you
ingest artificial sweetener with some food that
contains calories or sugar, and then later, you remove the food, and you just drink the soda, and your blood glucose goes up. Rather, it's a much worse situation. I'll make this in the
natural world context. If you ingest an artificial sweetener, say, drink diet soda while consuming foods that increase blood glucose, then later, even if you
just drink the diet soda, it's been shown that you
secrete much more insulin, the hormone that regulates blood glucose, in response to that diet soda. Studies have been done
in both adult humans and in human children. In general, when we say children, we mean human children, but just to be very clear
what we're talking about. Exploring consuming diet
soda with or without food, then later, consuming just the diet soda. And what they found was, having previously consumed
diet soda with food, and then later, only
consuming the diet soda, of course, there isn't an
increase in blood glucose, because they're not
bringing in any calories when they just drink the diet soda, but there is a significant
increase in insulin release, and that is serious in a terrible way, because increased release of insulin, and so-called insulin sensitivity, is the basis for type 2 diabetes. So much so, that in the
study with the children, consuming non-caloric
beverages in this way, first with food, and then on their own, led to increases in insulin
that made them pre-diabetic, and they actually had to halt the study. So I want to zoom out from this, and just really illustrate
the major findings, and then talk about
how this can be applied in the positive sense. I also want to mention what this means in terms of your consumption of artificial sweeteners of any kind. So first of all, the direct takeaway about
artificial sweeteners. Artificial sweeteners are not bad for you. I'm not going to say that. What I am going to say, is that whether or not
you ingest them alone, or you ingest them in
combination with food, or as part of foods that
raise blood glucose, is vitally important for
your insulin management. And the simple extractor
tool from this is, if you are going to consume
artificial sweeteners, it's very likely best to consume those away from any food that
raises blood glucose levels. So if you're going to enjoy
diet soda, be my guest, but do it not while consuming food, in particular, foods
that raise blood glucose. Because what these studies show, and I will provide references for these, is that they can vastly disrupt blood sugar management by way of the insulin glucose system, okay? And actually, I'll just
give you the reference now. This is a paper from Dana Small's lab. The first author is
Dalenburg, D-A-L-E-N-B-U-R-G. And the title of the paper is "Short-term Consumption of Sucralose With, nut Not Without Carbohydrate, Impairs Neural and Metabolic Sensitivity to Sugar in Humans". This is a paper published
in "Cell Metabolism" in March of 2020. I think it's a very important paper. And similar findings have
been addressed in mice, and in other studies. And now, because of this paper, there's now a bunch of other
groups working on this issue. There's some evidence previously
published in "Nature", an excellent top-tier journal. Sort of among the Superbowl
of top three journals, being "Nature", "Science", and "Cell". A paper published in
"Nature" a few years back showing that particular
artificial sweeteners can disrupt the gut microbiome, and have deleterious health effects. That result, I think, stands, although, there are some results that may not agree with that, depending on whether or not
the artificial sweetener is saccharin, or sucralose,
or aspartame, or stevia. That's the gut microbiome. But what we are talking about here is independent of the form of artificial or non-caloric sweetener, because it has everything to do with whether or not there is a match or a mismatch between the perceived taste, and the effect of the thing
that you are consuming on blood sugar and metabolism. So the first takeaway from this is, if you're going to consume
artificial sweeteners, it's really important that you do that not in conjunction with foods
that increase blood glucose. Second of all, it points to the fact, that the foods that we prefer, and the activation of the dopamine system, both through the gut, and at the level of conscious taste, in other words, what we
like, is very plastic. It's mutable, and we can change it. How can we change it? Well, earlier, I mentioned
a structure in the brain called the insula, this incredible structure that's
involved in interoception, and interoception of all kinds. In fact, just as an aside, a year or so ago, my lab published a paper showing that activity within certain
compartments of the insula of humans is responding to a heightened state of anxiety in the body. It can respond to changes
in our respiration, changes in our heart rate. So this is... Again, it's a readout
of our internal state, not just of taste, but of many, many different
aspects of the mechanics and chemistry of our internal
milieu within our body. All of the work that I
was describing previously has also been addressed
at the neural level. And using a broad brush
to explain these results, what we can say is, when there is dopamine increase, one sees activation of the
so-called nucleus accumbens, which is part of the so-called
mesolimbic reward pathway. If you'd like to learn more about the mesolimbic reward pathway,
and dopamine in general in humans and in animal studies, and all the various incredible and challenging things that
dopamine can do for us, there's a episode all about
dopamine that you can look up. It's easy to find at Hubermanlab.com. The increases in dopamine
associated with sweet taste and/or blood glucose
elevating foods and drinks, cause activation of the nucleus accumbens. That's not surprising. Also in the circuit is activation of the
so-called arcuate nuclei within the hypothalamus. These are areas of the hypothalamus that respond to hormones from the body, and respond to hormones and
neuropeptides in the brain, as well as neural signals in the brain, to drive us to eat
more, or to stop eating. So it's hypothalamus, nucleus accumbens. These are sort of the... Hypothalamus and the arcuate
being the motivating to eat, or motivating to stop eating. Both sets of neurons are contained there. There are other areas like the
lateral hypothalamus as well. But hypothalamus is
sort of the accelerator and the break on eating. And then the nucleus accumbens and dopamine release can be thought of as kind of a nitro boost, if
you will, like the kids say. Do the kids say that anymore? Anyway, a nitro boost to
increase what we call the gain or the volume of how much you
want more of something, okay? When dopamine is present, it's this kind of generic signal to go seek out more of
whatever caused that release. And then there's the insula. This very thoughtful, rational... Not really. It's not thinking. It's a brain area. You're thinking, but it's part
of the areas of your brain that are interpreting what's
going on in your body. Whether or not you feel good or not good. Whether or not you feel
anxious, excited, or fearful. It's integrating all that information. And fed into this entire circuit as well are the inputs from
your prefrontal cortex, which is your thinking, rational, neuronal structure, if you will, informing you, for instance, ah, well, I don't really
like salmon very much, or I'm not so crazy about kale, but it has omega-3s, or it's rich in these
polyphenols that are good for me. And if one decides that they
are going to eat these things, not just because they are good for them, but believe it or not, if one takes the perception or adopts the perception that
they are both good for you, and that in being good for you, they are good for your brain metabolism, and that you desire to be healthy, as crazy as it sounds, those subjective signals
of what you tell yourself about the foods that you're eating can actually impact how
those foods will taste, maybe not immediately, but eventually, and can impact the way in which your body utilizes those foods. Now, that might seem like
a absolute pipe dream. If I just imagine that I like mackerel, mackerel will start to taste good. I'm not saying that. I didn't say that you
could override yuck signals with this mechanism. I didn't say that you could take a food that would be absolutely noxious to you, or make you want to
vomit, and override that. However, foods that are
somewhat neutral to you can take on a different value based on the activation
of the dopamine system. And now, knowing what you know, there are a couple ways that
you could imagine doing that. First of all, you could,
in this so-called gedanken, or thought experiment, you could, for instance,
swap out sucralose, because sucralose is just a taste, right? It's an artificial sweet taste. You could swap that out, and insert kale, but eat the kale with something
that raises blood glucose to some degree or another. Now, I'm not encouraging
anyone to run out there and spike their blood
glucose glucose like crazy. And in fact, blood glucose
isn't really the goal. If you recall, the goal is to get neurons to be metabolically active
with that blood glucose, okay? That's what's actually rewarded at a sub-sub-conscious level, meaning at a deep subconscious level. But consuming these foods with other foods that increase blood glucose, and thereby, brain metabolism, or I suppose, if you're ketogenic, here in the ketosis, I don't know what the range of foods that are allowed on ketosis are, so I don't want to misspeak here, and say, cracker, which
would probably be a sin in the context of ketosis, and no knock against ketosis. I'm offering this, in part, because I think that there are
a number of people that have and can positively benefit
from a ketogenic diet. But for instance, if there's a food that you
want to consume more of, but that you find somewhat
meh, or mildly yuh, yuck, even pairing it with ketones, if indeed, you are using ketones
for your brain metabolism, 'cause that's what happens
on the ketogenic diet, over time, that food will be reinforced by the dopamine pathway. We know this from these studies where sucralose was the
substance paired with the glucose elevating. In other words, metabolically
elevating the food substance, or liquid substance. So how does one go about doing this? Well, first of all, I want to emphasize, that this experiment
actually has been done in a slightly different context. Studies by my colleague, Alia Crum, in the Psychology Department at Stanford have explored the bodily response, in terms of insulin release, and the release of other food
and eating-related hormones, as well as overall feelings
of satisfaction, et cetera, in groups of people
that drink a milkshake, and are either told that
it's a low calorie shake that contains various nutrients
that are good for them, or a higher calorie shake that has a lot of nutrients, et cetera. And what they found, was that the different groups, and here, again, I'm being very general with my description of these studies, but what they found, is that
the physiological response, the insulin response, the
blood glucose response, and the subjective measures of whether or not people
enjoyed something or not, were heavily influenced
by what they were told were in these milkshakes. So blood glucose would go up. Insulin would go up when people were told it
was a high calorie shake with lots of nutrients. Less so when people
ingested a shake that was, you know, that they were
told had less nutrients, and so forth. When in reality, it was
the identical shake. This is incredible. This is a belief effect. This is not placebo, right? A placebo effect is different. Placebo effect is in comparison. It's where the control condition actually influences outcomes to a same, or to some degree, just like
the experimental condition. This is not a placebo effect. This is a belief effect, where the belief and the
subjective thoughts about what a given food will do has a direct impact on
a physiological measure, like blood sugar and blood glucose. Okay, so let's zoom out
from this for a second, and think about how we
can incorporate this into adopting consumption of healthy foods that serve our brain health in
the immediate and long-term. And if you're wondering what those are, I listed them out at the
beginning of the episode, and their justification
for being on that list. What this means is, obviously, you want to
consume foods that you like, but because brain health
is very important, and many of the foods
that promote brain health, perhaps, are not the most palatable to you or desirable to you, the key would be to ingest the foods that you want to ingest more of simply because they're good for you, and not because they taste good to you, alongside foods that increase whatever fuel system you
happen to be relying on. I think that's the most nutritionally politically correct way to say it. So if you're keto, that would mean ketones, okay? If you're not ketogenic, and I think most people
probably are not in ketosis, or trying to maintain ketosis, but for instance, people that are on a
purely plant-based diet, that would be one set of foods. For people that are omnivores, a different set of foods. And for people that are carnivores, yet another set of foods. If you want to eat more
of a particular food because it's good for you, pair it with something in the same meal. You don't have to hide it physically, or in the flavor sense. You don't have to hide it
within that other food, but pair it with that other food that provides you a shift
in brain metabolism, because that's really what
your brain and you are seeking, even though you don't realize it. How long will this take? Well, according to the
data in humans on sucralose and the conditioning for
sucralose to have these effects, which, in many cases,
were detrimental, right? Because they were increasing insulin. But in this case, you're trying to hijack this conditioning
of food preference for healthy purposes, not with sucralose, but by ingesting things
that are good for you, then the data really point to the fact that even within a short period
of time of about seven days, but certainly within 14 days, that food will take on
a subjective experience of tasting at least better
to you, if not good to you. Now, I believe this has
important implications for much of the controversy and food wars that we see out there. Food wars being, of course, these groups that ardently
subscribe to the idea that their diet and the
things that they are eating are the foods that are good for us, and that are the most pleasureful, and the things that
everyone should be eating. We see this with every community
within the nutrition realm. Now, of course, there are
studies that point to the fact that certain foods and food
components are healthier, probably for us and for the planet, but you really see it on
both ends of the spectrum. You've got people who are
on a pure carnivore diet who are arguing with a
lot of biomedical evidence that that's what's best
for us and beneficial. And then you've got
people that are arguing the same general sets of arguments, but for a purely plant-based diet. And then I think most people fall into the omnivore category. What's very clear, however, is that what we consume on a regular basis and what leads to increases
in brain metabolism leads to increases in dopamine, and thereby our motivation to eat them. So what this really says, is that what we tend to do regularly becomes reinforcing in and of itself. And I think, in large part, can explain the fact that, yes, indeed, for certain people, a given diet not only feels good, but they heavily subscribe to the nutrient and kind of health beneficial
effects of that diet. And they often will
provide evidence for that, whether or not you ask them for it or not. But that's true of every subcategory within the nutrition realm. Again, this is not to take away from some of the beautiful data emphasizing that certain foods, and micronutrients, et cetera, are better for us, or worse
for us, and for the planet. That's not a debate I want
to get into right now. What this emphasizes, is that foods impact our
brain and its health, but they also impact
how our brain functions and responds to food, and that is largely a learned response. We can't completely
override, for instance, that certain foods evoke a
strong, [grunts] yuck component. Certain foods are truly putrid to us. I should just say, certain
things are putrid to us, and we should not consume them, right? At the far end of the spectrum, it's hard-wired for us to avoid those, because they can be dangerous for us. They can make us very, very sick. But it's also true, that if we continue to eat foods that are progressively sweeter and sweeter and highly palatable, it shifts our dopamine system, because it activates our dopamine system to make us believe that those foods are the only foods that can
trigger this reward system, and make us feel good,
and that they taste good. But after consuming foods
that perhaps are less sweet or even less savory, that are not what we would call highly, or I would say, nowadays,
it's super palatable foods, we can adjust our sense literally of what we perceive as an
attractive and rewarding food, and indeed, the dopamine system will reward those foods accordingly. I can't emphasize enough how much this learning
of associated food reward is important for not just understanding why we like the foods that we eat, and how to eat more of foods
that are healthy for us, and enjoy them, but it also speaks to the fact
that our brain, as a whole, is a perceptual device
trying to make guesses or estimations about what certain foods are going to do for us. So put simply, we don't just like sweet
foods because they taste good, we like them because they predict a certain kind of metabolic response. This is important also, because Dana Small, and Ivan de Araujo, and others have been exploring whether or not people, for instance, that have type 2 diabetes, or that suffer from any number of different metabolic disorders, whether or not somehow these food reward systems
are permanently disrupted, and through a beautiful set of experiments that have been done by mainly
by Dana Small's group at Yale, but also by the de
Araujo group and others, exploring how the reward
pathways are altered in various metabolic disorders, et cetera, people suffering from type 2 diabetes. We don't have time to go
into all those data now, but the takeaway is, that food preference, and the ability to reshape these circuits is not disrupted in these people to the point where it can't be rewired, and that's very encouraging, because what it means is that, for people that are suffering
from these syndromes, through some simple
alterations in dietary choice, provided those are carried out over time and in the correct way, by pairing with the foods
that will appropriately shift metabolism of the brain, one can actually rewire what they consider not just palatable, but attractive as foods. If you want to learn
more about food reward and food reinforcement, 'cause it turns out, those
are slightly different things, there's a wonderful review
written by Ivan de Araujo. They have a middle author,
Mark Schachter, and Dana Small. It's called "Rethinking Food Reward", and it was published in the
"Annual Reviews of Psychology". You can find it very easily online. It was published in 2019. And it's a beautiful, deep dive, although, quite accessible to most people, about how different foods, and the way that we perceive them impacts our brain and body, and why we like the things we like, and how to reshape what we like. So once again, we've done a
fairly extensive deep dive into food and your brain, focusing first on how particular foods and compounds within foods that are available also
through supplementation can impact immediate and
long-term brain health. Came up with a relatively short list of what I would call super foods, only because there are
ample data to support their role in enhancing short
and long-term cognition, and neuronal health, and so on. And we also talked about food preference, and why particular tastes, and particular events within the gut, and particular events
within the brain combine to lead us to pursue particular foods, and to avoid other foods, and how you can leverage those pathways in order to pursue more of the foods that are going to be
good for you, and good, not just for your brain, but for your overall body health, and to enjoy them along the way. If you're learning from, and
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beginning of the episode. we also have a Patreon. It's patreon.com/andrewhuberman. And there, you can support the podcast at any level that you like. During today's podcast, and on
many other previous episodes, we talked about various supplements. One of the major issues with supplements is that supplement
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contained in the capsules, and pills, and powders
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Disclaimer, I am by no means either side of the fence on this topic. I assume they are referring to the article Gut-microbiota-targeted diets modulate human immune status. While the study did have significant findings as Huberman refers to, Huberman doesn't mention the significant length of limitations and issues that this study had which is fairly irresponsible. Definitely research in a valuable direction and expanded the literature, but a lot more research needs to be done on the topic before such solid conclusions are drawn. Interesting article all the same and people should check out the article if they're interested in the topic. https://doi.org/10.1016/j.cell.2021.06.019