Huberman Lab - Nutrients For Brain Health & Performance

Welcome to the Huberman Lab Podcast,

where we discuss science

and science-based tools for everyday life.

I’m Andrew Huberman,

and I’m a professor of neurobiology and ophthalmology

at Stanford School of Medicine.

Today, we are 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 p.m.

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 a.m. one day and end it at 6 p.m.

and then the next day start at noon

and end it at 8 p.m.

and the next day started at 2 p.m.

and ended at 10 p.m. 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 Athletic Greens.

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I’ve done a couple of episodes now

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Today’s episode is also brought to us by Element.

Element is an electrolyte drink

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That means the exact ratios of electrolytes are in Element,

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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 have done several episodes,

including the Master 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 preexisting 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

in order 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 might 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 very 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 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 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 and walnuts

and 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 to 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 mean, I’m making this face because 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 cardiovascular 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.

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.

And 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 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 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 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 areas.

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 eggshell,

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 there’s 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 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 is, 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 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 of 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.

That 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

because 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.

So 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 Rochelle, 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?

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, you know, 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 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 purplish 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,

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 five and a half

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 phosphodidylserine, 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.

You know, 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 a 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, excuse me,

is a very serious issue for which glutamine appears

to be able to offset some of the negative symptomology.

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 the 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, 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 effects.

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,

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, braising of meats and braising 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 are 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 that 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 Zucker, Z-U-K-E-R,

he’s a absolutely phenomenal neuroscientist

at Columbia University in New York.

Studies done by the Zucker 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 kinds 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 taste to bitter

or sweet taste 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, 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 with it 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 particular tastes 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

because I don’t particularly like fish.

I’ve had a few, you know, meals that included fish

that were pretty good,

but none of them were memorable in the kind of positive way

like some other events in my life are memorable.

But by way of these circuitries

and the way they link up with one another,

it’s actually possible to rewire one 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.

So 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.

Here’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,

and doesn’t have to be distended,

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 Borges.

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 Borges at Duke University

who discovered that these cells reside within the gut

and place little processes,

their 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 no-dose ganglion.

The no-dose ganglion is a cluster of neurons

that then go 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.

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,

because that’s the environment that they settle down into.

This is work that was carried out

by my colleagues, Justin Sonnenberg,

which is in the laboratory upstairs from me,

as well as Chris Gardner and others at Stanford.

They’re 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 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

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 taste,

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

and the sensations that make us go,

mm, or ugh, or eh, the yum, yuck, 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 Arrujo and Dana Small.

Ivan de Arrujo 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

because 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.

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 Arrujo’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 hardwired,

meaning immutable and unchangeable, or softwired.

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 hardwired 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 hardwired 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 now have 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.

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 pleasurable.

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.

If you, 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 two 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 foods

or as part of foods that raise blood glucose

is vitally important for your insulin management.

And the simple extract or tool from this

is if you’re 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 Dallenberg, D-A-L-L-E-N-B-E-R-G.

And the title of the paper

is Short-Term Consumption of Sucralose

With but 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,

excellent top tier journal,

sort of among the Super Bowl of top three journals

being Nature, Science, and Cell.

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,

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

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 brake 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 of 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 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-subconscious 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,

you’re 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, you know,

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 yuck even,

pairing it with ketones,

if indeed you are using ketones for your brain metabolism,

because 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 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, Aaliyah 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 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 points 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 pleasurable

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

with 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 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?

And that’s at the far end of the spectrum,

it’s hardwired 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 Arrujo and others have been exploring

whether or not people, for instance,

that have type two 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 mainly by Dana Small’s group at Yale,

but also by the de Arrujo group and others,

exploring how the reward pathways are altered

in various metabolic disorders, et cetera,

people suffering from type two 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,

because it turns out those are slightly different things,

there’s a wonderful review written by Ivan de Arrujo.

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.

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