Welcome to Huberman Lab Essentials,

where we revisit past episodes for the

most potent and actionable science-based

tools for mental health, physical

health, and performance.

I'm Andrew Huberman, and I'm a professor

of neurobiology and opthalmology at

Stanford School of Medicine. Today we

are going to discuss sugar in

particular, how our nervous system

regulates our sugar intake and our

seeking of sugar. We are going to place

sugar into its proper context. The way I

want to start off by doing that is to

tell you a little bit of what happens

when we eat and a little bit of what the

brain does to respond to those events.

So what happens when we eat? Let's just

take a what I call top contour view of

the hormonal response to ingesting food.

Anytime we eat, that is the consequence

of a number of things that happened

before we ate. There's a hormone in our

brain and body called ghrein spelled g h

l i n. Ghrein is a hormone that

increases depending on how long it's

been since we ate last. Okay? So, the

longer it's been since we had a meal,

ghrein levels are going to be higher and

higher and higher. And it essentially

makes us hungry by interacting with

particular neurons in an area of the

brain called the arcuate nucleus of the

hypothalamus and some other areas as

well like the lateral hypothalamus. And

then when we eat typically what happens

is ghrein levels go down. So, it's a

very logical system. Now when we eat,

assuming that we eat carbohydrates, but

even if we just eat some protein and

some fats, we will experience a slight

or in some cases a large rise in blood

glucose. Blood glucose is simply blood

sugar. And the body and brain, we should

say particular the nervous system

doesn't function well if blood sugar is

too high or too low. So as a consequence

we have another hormone which is

released from the pancreas which is

called insulin which helps regulate the

amount of glucose in the bloodstream.

Now one of the chief organs for glucose

utilization is the brain. Neurons are

tremendously metabolically active and

their preferred mode of metabolism is

glucose metabolism. The same thing is

also true for the neurons in your body.

The way that you are able to move the

limbs of your body, the way you are able

to perform exercise or movement of any

kind for that matter is because neurons

called motor neurons send electrical

potentials to the muscle fibers. Those

neurons are also very metabolically

demanding, especially when you're doing

demanding types of physical work. But

also, deliberate thought, deliberately

controlling the way that your brain and

body is moving requires more glucose

uptake, more energy in those very

neurons. And this is also why after

doing a long bout of exercise, you might

be tired. But also, if you do a bout of

skill learning of any kind, or if you've

been reading and thinking about what

you're reading, or if you had a intense

conversation with somebody where you're

really forcing yourself to listen,

that's work. And that work requires

glucose uptake by neurons both in the

brain and in your body. Now that we've

established that glucose is the

preferred source of fuel for the nervous

system, I'd like to concentrate on a few

of the other types of sugars that we

ingest on a common basis and the impact

that those have on brain function and

body function. I'd particularly like to

focus on fructose. Fructose, of course,

is found in fruit. It's also found in

the infamous high fructose corn syrup,

which we will talk about today. It's

worth pointing out that the

concentrations of fructose in fruit is

quite low compared to the concentrations

of fructose in high fructose corn syrup.

Typically, the amount of fructose

fructose I I think is the proper

pronunciation that people are always

correcting me. Fructose

is anywhere from 1% to about 10%. Now,

high fructose corn syrup is a different

issue. And too much consumption of

anything, but fructose included, can be

a problem for the ways that it impacts

the neural circuits that process sugar.

Not just glucose, but fructose. One of

the key distinctions between glucose and

fructose is that fructose most likely

cannot directly access the brain. It

actually needs to be converted into

glucose in the liver. And the way that

conversion occurs feeds back to a set of

hormones and neural pathways that we

talked about earlier which have a lot to

do with appetite. And to just summarize

what is now a lot of very solid data,

fructose and specifically fructose has

the ability to reduce certain hormones

and peptides in our body whose main job

is to suppress ghrein. So although I and

I think pretty much everyone out there

say for a few individuals agrees that

calories in calories out is the

fundamental principle of weight loss m

weight maintenance or weight gain.

Ingesting fructose shifts our hormone

system and as a consequence our neural

pathways within our brain the

hypothalamus to be hungrier

regardless of how many calories we've

eaten. So, current recommendations for

most people are to eat more fruits and

vegetables, but for those of you that

are trying to control your hunger,

ingesting a lot of fructose is probably

not going to be a good idea. Certainly,

ingesting it from high fructose corn

syrup is not going to be a good idea

because of the enormous percentages of

fructose in high fructose corn syrup,

50% or sometimes even more. Fructose

provides a bridge for us between a

particular kind of sugar hormone

function

in this case ghrein and the hypothalamus

which leads us to the next question

which is what is it about sugar that

makes it such an attractive thing for

us? Why do we like it so much? And the

obvious answer that most people arrive

at is well it just tastes really really

good. But that's actually not the way it

works. The rewarding properties, as we

say, of sugar, whether or not they come

in the form of sucrose or fructose or

foods that increase glucose to a a very

high level, actually is not just related

to the taste of the foods that produce

that elevation in glucose, sucrossse, or

fructose. It is in part, but that's only

part of the story. And the rest of the

story once you understand it can

actually place you in a position to much

better control your sugar intake of all

kinds, but also your food intake in ways

that can allow you to make much better

choices about the foods you ingest. So

now I want to take us on a journey into

the nervous system to explain the

pathways in the brain and body that

regulate our appetite for sugar. Now,

keep in mind what I already told you

before, which is that when we ingest

foods, they're broken down into various

components, and glucose is going to be

shuttled to the brain and of course to

other neurons in our spinal cord and

elsewhere and to our muscles, etc., in

order for all of those cells and organs

and tissues to be able to function. The

fact that so many cells and organs and

tissues require glucose in order to

function has led to a situation where

you have dedicated neural machinery,

pieces of your brain that are almost

entirely, if not entirely devoted to

seeking out of sugar or foods that

contain sugars and to make sure that you

not only seek those out, but you know

where those foods are and that you

ingest more and more and more of them.

And there are two main ways that these

neural circuits work. In fact, we can

say that there are two neural circuits

entirely that work in parallel. In the

case of sugar consumption, the two

parallel pathways involve one pathway

related to the actual taste and the

perception of sweet tastes that lead not

just you but every animal that we're

aware of to seek more sweet containing

foods.

The other parallel pathway is related to

the nutrative component of sweet foods.

Meaning the degree to which a given food

will raise blood glucose. I want to

repeat that one pathway in your brain

and body is devoted to getting you to

seek out sweet tasting things that you

perceive as sweet and another parallel

pathway is devoted to getting you to

seek out foods that lead to increases in

blood glucose. It just so happens that

the foods that lead to big increases in

blood glucose typically are associated

with that sweet taste. Now, this is

distinctly different than the neural

pathways that control seeking of savory

foods or salty foods or spicy foods for

that matter or bitter foods. The sweet

pathway is what we would call hardwired.

It exists, as far as we know, in every

mammal. Basically, getting sweet stuff

into the body might seem like it has a

lot to do with the taste, but it has

just as much to do with the nutrative

components that sweet tasting foods

carry and the fact that your nervous

system and so many cells in your brain

and body run on glucose. If you recall

earlier, I said even if you ingest

fructose, fructose can be converted into

glucose in the liver. The fundamental

thing to understand here is that when

you think you want a piece of chocolate

or you think you want a piece of cake or

you're craving something sweet, you are

both craving the taste and your neurons

are literally craving the nutrative

components that arrive with with that

taste. Two parallel pathways. One of the

parallel pathways has to do with

conscious perception. So when you ingest

something sweet, very quickly there are

signals sent from those neurons in your

mouth to brain areas that cause you to

seek out or at least pay attention to

the source and the abundance of those

sweet things. They literally change your

perception. Does that mean that you

should never ingest anything sweet? No.

Certainly I'm not saying that. Everyone

has to decide for themselves what the

appropriate amount of sugar intake is.

But I find it remarkable when people

say, "Oh, you know, I need to get my

sugar fixed or I need to have my

chocolate or I need to have a little bit

of something to just kind of take care

of that sugar appetite." Because in

taking care of that sugar appetite,

maybe for the very disciplined of you,

you can just have that one piece of

chocolate and it's great and you can

relish in it. But it does shift the way

that you perceive other foods as well.

And the way it does that is through our

probably if you're a listener to this

podcast now old friend but incredible

neurom modulator dopamine. Dopamine is a

molecule that is released from several

places in the brain. There's a so-called

misolyic reward pathway which is a whole

set of places in the brain or circuits

designed to get us motivated and craving

and in pursuit of things. And then of

course there are areas of the brain that

are involved in movement that are linked

up with those areas involved in

motivation. And that makes perfect

sense. Why would you have a brain area

involved in motivation if you couldn't

actually do something with that

motivation? When we ingest something

sweet, the perception of that sweet

taste increases dopamine and the

misolytic reward pathways which then are

conveyed to pathways for motor behavior

and in general place us into modes of

focused action toward getting more of

whatever was sweet. But if you

understand the way that dopamine works,

what you'll realize is that when this

dopamine pathway is triggered, it tends

to create not the sensation or the

perception of satiety of feeling like

something is enough, but rather to

produce the sensation of wanting more.

In fact, we can say that the longer it's

been since you've indulged in something

that you really enjoy or would like, the

greater the dopamine you will experience

when you finally engage in that behavior

or indulge that thing, ingest that

thing. Now, I again, I'm not saying that

you shouldn't pursue pleasurable things.

These dopamine pathways are not evil.

They're not bad. But once you understand

the way they work, you can leverage them

to your advantage as opposed to them

leveraging you to their advantage. Now

there's the second pathway. The second

pathway is what's called the

postingestive

reinforcing properties of sugar, which

is really just a fancy nerdspeak way of

saying there are events that happen with

your within your stomach and below your

conscious detection that are also

driving you to seek out sweet tasting

things independent of their taste. and

foods that increase blood glucose

independent of their taste. And here's

how it works. We all have neurons within

our gut. These neurons have a name. They

are called neuropod cells. Neuropod

cells were famously discovered by

professor Dr. Diego Bahorquez at Duke

University. And these cells respond to,

among other things, to the presence of

sugar within the gut. These neuropod

cells send electrical signals through a

particular highway within the vagus to

the so-called noo's ganglen. This is a

cluster. A ganglen is just a cluster of

neurons. And then the nose ganglion

sends on information to the nucleus of

the solitary tract. The nucleus of the

solitary tract is very important for

understanding sugar preference. So we've

all heard of hidden sugars, meaning the

sugars that manufacturers have put into

foods and disguised them with other

flavors. The savory foods are often

laden with these hidden sugars that we

can't register as sweetness but trigger

the neuropod cells which then further

trigger dopamine which make us want more

of them. Now we may be able to resist

eating more of them but it makes us

crave more food in general. Now we will

talk about ways to regulate this pathway

to sort of intervene in this

subconscious pathway.

But for now, I'm hoping that just the

understanding that we all have this

pathway. This is hardwired into our body

could potentially allow people to better

understand why is it that their cravings

are so intense that it's not necessarily

just about the taste of that food. And

when you consider this, you start to

realize that there are multiple

mechanisms hardwired into us that make

it especially hard to not eat the sweet

thing or to not eat the food that we're

craving. And indeed that's the case. We

have two major accelerators. It's like a

car with two accelerators. And we will

talk about the brakes, but two ways that

really get us into forward motion toward

pursuing the consumption of sweet foods.

Now, some of you have probably heard of

the so-called glycemic index, which is

basically a measurement of how high and

to some extent how fast blood sugar

rises in response to ingesting

particular foods. And very broadly

speaking, we can say that there are low

glycemic index foods of less than 55

typically is the measurement or medium

glycemic index foods which go from about

55 to 69 and then so-called high

glycemic foods which are above 70. And

of course there's additional nuance

related to glycemic load and many more

features of the glycemic index. a couple

of things to understand about how the

glycemic index is measured. And then I'd

like to just briefly talk about how the

glycemic index can be leveraged to

shortcircuit some of the neural circuits

that would otherwise lead us to crave

and perhaps even ingest sugary foods.

First of all,

measurements of glycemic indices of food

are typically made by having people

ingest those foods in isolation. And in

general we can say that anytime we

ingest fiber and or fat lipids along

with a particular food it will reduce

the glycemic index of that particular

food. Either the absolute level of blood

glucose that a particular food causes or

the rate at which that elevation in

blood glucose occurs. Okay? And this is

why there are some seemingly paradoxical

aspects to sweet stuff in terms of

glycemic index. For instance, ice cream

has a lower glycemic index provided it's

ice cream that includes fat, which I

hope it would because that's the good

tasting ice cream in my opinion compared

to something like mangoes or table

sugar. The glycemic index is not

something to hold wholly in most cases

because most people are not ingesting

foods in isolation. Now, why am I

telling you about the glycemic index?

Well, if we zoom out and take our

perspective on all of this discussion

about the glycemic index through the

lens of the nervous system and we remind

ourselves that neurons prefer glucose

for energy and that all sweet things or

things that we perceive as sweet, but

also sweet things that are ingested and

registered by those neuropod cells in

our gut trigger the release of dopamine

and trigger these neural circuits to

make us want to eat more of these foods.

What we start to realize is that a sharp

rise in blood glucose or a very high

degree of elevation in blood glucose is

going to be a much more potent signal

than will a more moderate rise in blood

glucose or a slower rise in blood

glucose. And so for those of you that

are trying to reduce sugar intake and

you want to do that through an

understanding of how these neural

circuits work and you want to

shortcircuit some of the dopamine

release that's caused by ingesting

sugary foods, it can be advantageous to

ingest sweet foods in combination with

foods that reduce glycemic index or

reduce glycemic load. So that might mean

making different food choices. So paying

attention to sweet tasting foods that

can satisfy sugar cravings but do not

have as steep or I should say do not

cause a steep a rise in blood sugar. Or

it could mean consuming other foods

along with sweet foods in order to

reduce the glycemic index and thereby

slow or blunt the release of dopamine.

So, if you really wanted to adjust your

sugar cravings and you really still want

to inest some sugary foods, you probably

would be better off combining fiber with

that sugary or sweet food. So, what

we're really talking about here is

trying to reduce the dopamine signal

that is the consequence of ingesting

sweet foods. And we're talking about

doing that through these different

parallel pathways. Not just by

preventing sweet taste, but also by

preventing the post-ongestive effects of

sweet foods. And of course, the backdrop

to all of this is that most of us,

again, most of us, not all of us, should

probably be ingesting fewer refined

sugars. So, what are some ways that we

can reduce our sugar cravings and

ideally ways that we can do that that

also benefit us in other ways, both

nutritionally and from the neuroscience

standpoint. The fact that these neuropod

cells and I should say other neurons

within the gut respond very robustly to

the presence of particular amino acids

is also a potential lever by which one

could reduce sugar cravings. And there's

an interesting literature around the

amino acid glutamine in particular

supplementing with the amino acid

glutamine as it relates to sugar

cravings and certainly as it relates to

other aspects of the gut in particular

leaky gut. The use of supplemental

glutamine to try and treat leaky gut is

not a new phenomenon. There are other

approaches too of course but there are

many people who are experimenting with

supplementing with glutamine several

grams per day often even you know five

grams distributed through three or four

different servings throughout the day in

as a way to blunt their sugar cravings.

Now, there has not yet been a

large-scale clinical trial using

glutamine to reduce sugar cravings, but

the results of the few studies that I

looked at, as well as my understanding

of the logic of these neural circuits,

including the neuropod cells, brings us

to a conclusion that it makes sense why

if there's a population of neurons

within our gut that responds very

robustly to the presence of sugar, fatty

acids, or amino acids that the intake of

particular amino acids would allow the

dopamine pathways that might otherwise

be triggered by sugar to be triggered by

something like glutamine, which has very

few or no calories. I know some people

who actually take glutamine and mix it

with full fat cream and take it kind of

like a shot of full fat cream, which

sounds absolutely delicious. By the way,

glutamine is a little bit chalky, so

it's not that great tasting to ingest

with sugar. I should mention if you do

try and take this approach of ingesting

glutamine to reduce sugar cravings, you

want to increase the amount of glutamine

that you take somewhat gradually. It can

create some gastric distress if you

just, you know, I certainly wouldn't

take a big tablespoon of it, throw it in

water and chug it down three times a

day. Please also realize that there's an

entire literature devoted to the

potential hazards of increasing

glutamine if you have a pre-existing

cancer. So, if you have cancer or you're

cancerrone, I would really discourage

you from this approach. In any case, as

always, talk to your doctor. Now, there

are other ways to reduce sugar craving,

and there are certainly ways to reduce

the sharp rise in blood glucose that can

occur when we ingest sugary sweet foods

or even just an abundance of

carbohydrate foods. And there are a huge

number of these things. I'm going to

sort of layer up through the the ones

that you might find in your cupboard at

the grocery store and then get into some

of the more um extravagant or I should

say um esoteric ones. many of which

however um can be quite potent. The

first of which um is simple lemon juice

right or lime juice. Regardless,

there are now data pointing to the fact

that lemon juice and lime juice a couple

tablespoons or so if ingested before or

even during or even after consumption of

sugary foods or I should say foods that

sharply increase blood glucose or large

carbohydrate meals can actually blunt

the blood glucose response. And I did

see that when I did my own experiments

on myself with continuous glucose

monitor. It was kind of fun to do those

exper experiments. Um I preferred to do

those experiments by eating somewhat

larger meals of things that didn't

contain a lot of sugar. I saw some big

increases in blood glucose in certain

instances and then I would ingest some

some lemon juice or lime juice typically

mixed in with water and sure enough you

could see a blunting of the blood

glucose response. And of course this was

real time continuous hence continuous

blood glucose monitoring. When you

ingest lemon juice or lime juice, the

mechanism by which it blunts blood

glucose is probably twofold. One is

probably through the post-ongestive

effects of glucose in the gut, meaning

the way in which sugars are interacting

with neurons and other components of

your gut circuitry to impact things like

gastric emptying time, to impact things

like the firing of those neuropod cells

and their signaling to the brain. But

almost certainly it has something to do

also with the perception of sour taste

on the tongue. We didn't go into this

too much today, but you of course don't

just have sweet taste receptors in your

mouth. You also have bitter taste

receptors. You have salty taste

receptors. You have sour taste receptors

in your mouth and on your and of course

that means your tongue and pallet. And

those are interacting. If you ingest a

substance that's just sweet or mostly

sweet,

that causes a certain set of effects on

your blood glucose, but also your brain,

dopamine, and the other neural circuits

of your brain. If you also ingest

something that's sour, like lemon juice

or lime juice, it adjusts the output of

those neural circuits in your brain. So

again we have a situation where we have

two parallel pathways. One that's

post-ongestive coming from phenomenon

within our gut neurons but also things

like gastric emptying time the clearance

and the transfer of food and the

conversion of food into particular

nutrients and the circulation of glucose

in your bloodstream and how it gets into

the brain. But also simply by ingesting

something sour you are changing the way

that sweet things impact your brain. And

so I think it stands to reason that the

lemon juice, lime juice effect is not

going to be magic. It's going to have

everything to do with the way that

ingesting sour foods can adjust the

neural response to taste of sweet foods.

And in fact, we know based on the

beautiful work of Charles Zuker at

Colombia Medical School that that's

exactly what happens. Now, some of you

have probably heard that cinnamon can be

a useful tool for controlling blood

sugar. And indeed, that's the case. It's

very clear that cinnamon can adjust the

rate of glucose entry into the

bloodstream possibly by changing um the

rate of gastric emptying. It might slow

the rate of gastric emptying and thereby

also reduce the glycemic index of

particular foods. So I suppose if I were

going to eat a mango and I hadn't just

done a bunch of hard training, I might

sprinkle some cinnamon on it here. I

always enjoy kind of coming up with new

ideas of ways that I can eat foods

during these podcasts. I do want to

provide a cautionary note about

cinnamon. However, cinnamon contains

something called couadin which can be

toxic at high levels. So, you don't want

to ingest more than about a teaspoon,

maybe a teaspoon and a half of cinnamon

per day um because you'll start to

exceed the threshold at which cinnamon

could um start to be problematic. So,

we've talked about lemon juice and lime

juice and cinnamon. These are kind of

common place in many kitchens.

Then of course we can venture into the

more esoteric or I would say the more

advanced tools for adjusting sugar

intake. The one that comes to mind is of

course bourberine. Using bourberine is a

serious step. You should absolutely talk

to your doctor about it. It is true that

if you ingest bourberine your blood

glucose will plummet. And I point that

out because I've actually tried it

before. It gave me brutal headaches and

I felt really dizzy and I felt like I

couldn't see straight. And actually I

couldn't see straight. Why did it do

that? Well, it made me hypoglycemic. It

actually drove my blood glucose down too

far. And the reason it did that is that

I took bourberine on an empty stomach.

If I took bourberine along with a very

large meal that included a lot of

carbohydrates, then I felt perfectly

fine on even up to 750 milligrams or a

gram of bourberine. But again, talk to

your doctor. I would place bourberine

and of course metformin and globenomide

in the kind of the heavy hitting potent

tools for regula regulating blood

glucose. And there are some other

substances like um sodium caprate which

are known to augment the effects of

bourberine via thempk pathways. They

basically can increase the ability for

bourberine to have its glucose lowering

actions. But that of course is getting

into the really potent what I would call

sharp blade tools for controlling blood

glucose. And listen, anytime you're

dealing with blood glucose, you are

dealing with the brain's preferred

source of fuel. And anytime you're

dealing with the brain's preferred

source of fuel, you have to be

especially cautious about depriving the

brain of what it needs. These substances

like bourberine are very, very potent.

And you need to take them seriously.

There is yet another tool for

controlling sugar cravings and the

neural circuits that regulate sugar

craving and its downstream consequences.

And this tool is what I would call a

high performance tool, but it's one that

you probably didn't suspect, and that's

sleep. I've done extensive episodes

about sleep. We actually have an episode

called Master Your Sleep. Uh you can

find that episode easily at

hubermanlab.com. It's available in all

the various formats, YouTube, Apple,

Spotify, etc. And provides a lot of

tools. And on social media, I provide a

lot of tools. What is the role of sleep

in sugar metabolism, sugar hunger, and

the way that the brain regulates those

things? Well, there's a really exciting

study that came out just last year. This

study was published in the journal Cell

Report, Cellpress Journal, excellent

journal. The reason I love this study so

much is it involved having people, so

yes, this was done in humans, sleep in

the laboratory. That's not unusual.

There's a sleep lab at Stanford, there's

sleep labs elsewhere. What they did was

they actually measured from the breath

of these people and they extracted from

their breath the metabolites that would

allow them to understand what sorts of

metabolism was occurring in these

people's bodies at different phases of

sleep. They actually did this every 10

seconds throughout the entire night.

What they discovered was that each stage

of sleep was associated with a very

particular signature pattern of

metabolism and particular phases of

sleep are associated with sugar

metabolism or more with fat metabolism

or more with other aspects of

metabolism. And the reason why I think

this study is important to discuss in

the context of today's discussion about

sugar in the brain is that many people

have experienced

the effects of disrupted sleep on their

appetite. And in particular, it's been

reported that when people are sleepd

deprived or the quality of their sleep

is disrupted, their appetite for sugary

foods increases. Now, we don't want to

leap too far from this study to sugar

metabolism and the neural circuits

controlling sugar metabolism, but I will

say this. There is now a plethora of

data pointing to the fact that getting

quality sleep each night helps regulate

not only appetite, but also the specific

forms of metabolism that drive specific

appetites. So we can't overstate the

importance of getting regular sufficient

amount of high quality sleep at least

80% of the time not just for sake of

immune system function for clear

thinking etc but also for properly

regulating our metabolism including our

sugar metabolism. Thank you for joining

me for this discussion about sugar and

the nervous system and how they are

regulating each other in both the brain

and body. And last but certainly not

least, thank you for your interest in

science.