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 going to discuss sugar,

in particular, how our nervous system

regulates our sugar intake and our seeking of sugar.

We’re also going to discuss

how sugar regulates our nervous system.

And as you’ll soon learn,

sugar really impacts our brain and body

by two main mechanisms.

One of those mechanisms is based on the sweet taste of sugar,

which itself is rewarding.

Even if you’re not much of a sweet tooth,

I confess I’m not,

most people enjoy sweet tastes more than bitter tastes.

And the sweet taste of sugar and its various forms

is strongly reinforcing,

meaning it triggers the activation of neurons,

nerve cells in the brain and body

that make us want to consume more of that sweet substance.

Incidentally, sweet tastes also make us want

to eat more of other substances as well.

You may be familiar with that phenomenon.

Now, sugar also triggers mechanisms in the brain and body

based on its nutritive content,

independent of its sweetness.

What that means is that the actual caloric content

and the way that sugar interacts with your nervous system

at a subconscious level without your awareness

also impacts your craving and seeking of sugar

and other foods.

Today, we are going to discuss what happens

when you ingest sugar in terms of your body’s reaction

and your brain’s reaction.

We’re also going to talk about what happens

when you don’t ingest enough sugar.

Because as it turns out,

sugar is such a powerful fuel for the brain

that under conditions where people don’t ingest enough sugar

or where their so-called blood glucose,

which is basically blood sugar of a particular form,

gets too low, their neurons don’t function as well.

That said, there are conditions of very low blood sugar

in which neurons can function even better.

Today, we are going to talk about the ins and outs,

the ups and downs of sugar

as it relates to your nervous system.

And by the end of this episode,

I’m confident that you’ll have a much clearer picture

as to how much sugar you should be ingesting,

whether or not you should avoid sugars

that you’re currently eating.

And you will certainly understand much, much more

about the energy and fuel sources that your brain relies on,

which I’m certain will allow you

to make better informed choices

about the foods you eat and avoid

toward mental health, physical health, and performance.

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.

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Okay, let’s talk about sugar.

Let’s talk about how sugar impacts your brain

and how your brain impacts your pursuit

or your avoidance of sugar.

Let’s get a few things out of the way first.

The first thing is that there’s nothing

inherently bad about sugar.

I know the word sugar gets a bad rap nowadays,

and indeed, you’re going to hear over and over again

during this podcast that consuming a lot of refined sugars,

in particular high fructose corn syrup,

is known to have a very large number

of bad effects on the brain and body.

I don’t know that there’s anyone

that really debates that anymore.

Even if we just agree, and I think we should all agree,

on the so-called calories in, calories out principle, right?

It’s a principle of thermodynamics

that if we ingest more energy than we burn,

we are going to gain weight.

If we ingest less energy than we burn,

we are generally going to lose weight.

And if the two things are in balance,

ingestion and burning of energy,

well, then we’re going to maintain weight.

So everyone agrees on that.

I agree on that, but beyond that,

there are a number of ways in which particular nutrients,

in the case of today’s episode, sugar,

impact the way that the brain works,

such that we tend to seek out more of particular nutrients.

For instance, if we eat sugar,

there are two or at least two mechanisms

by which we will crave more sugar.

I think most people are aware of that experience,

but today I’m going to explain exactly how that works.

But also that when we ingest sugar,

it has a bunch of different effects

on the way that our neural circuits work

that can allow us to be more or less focused,

more or less agitated, more or less happy,

more or less depressed in some cases.

So today, as we explore this thing we’re calling sugar,

we’re going to explore that mainly in the context

of the nervous system,

but also in the context of how the nervous system

regulates many, many functions and behaviors

that are important to all of you.

Your ability to think, your ability to exercise,

your ability to gain weight, lose weight,

whatever your goals might happen to be.

Sugar plays a critical role in achieving those goals.

And in some cases, if you’re ingesting too much

at the wrong times or the wrong forms,

sugar can actually impede those goals.

In fact, sugar can prevent all the right behaviors

from allowing you to achieve the goals that you want.

So today 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?

Well, I’ve done an entire episode on metabolism.

So if you’re interested in the full cascade of hormonal

and neural events that occurs when we eat,

please check out that episode.

But for sake of today’s discussion,

let’s just take a, what I call top contour view

of the hormonal response to ingesting food.

Now, 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 ghrelin,

spelled G-H-R-E-L-I-N.

Ghrelin 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,

ghrelin 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.

You don’t need to know the names of those brain areas,

but if you’d like to know them, there they are.

Ghrelin increases, it tends to make us hungry.

And then when we eat,

typically what happens is ghrelin 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.

So even if you were to ingest an entire cup,

an eight ounce cup of pure table sugar,

which would send your blood glucose very, very high,

assuming that you have a normal insulin response,

that you’re not diabetic,

that insulin response would help clamp

that blood glucose level so that it did not cause damage

to your brain and body.

Because if blood sugar goes too high,

it’s actually toxic to neurons

and other cells of your body can kill them off.

And neurons of the central nervous system,

meaning the brain and spinal cord,

once they are dead, they do not come back.

So your biological systems understand this

at a biological level that is,

and prevent that death of cells due to high blood sugar

by keeping insulin around in order to clamp blood glucose.

Diabetics, we call them type one diabetics

who don’t make insulin have to take insulin when they eat,

in particular, when they eat foods

that raise their blood sugar,

specifically to avoid that neurotoxicity

and the other deleterious effects of high blood sugar.

Okay, so ghrelin is a hormone that goes up

the longer it’s been since we’ve eaten.

It tends to stimulate hunger.

When we eat, ghrelin is suppressed.

Blood glucose typically goes up,

especially when we eat a carbohydrate-containing meal.

When blood glucose goes up, it’s regulated in the body,

meaning its peaks and its valleys

are more or less smoothed out.

And that glucose is sequestered.

It’s taken away where it needs to be taken away.

And in certain locations, it’s delivered to cells

so that those cells can use the glucose.

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.

In other words, neurons basically run on sugar,

which is not to say that you should eat a lot of sugar.

As you’ll see today, there are states of mind and body,

for instance, fasted states in which people report

having immense amounts of mental clarity

and their blood glucose is actually quite low.

So it is simply not the case

that the more sugar that you ingest,

the better that your brain will function.

But it is the case that for most people,

meaning people who are not on a ketogenic

or very low carbohydrate diet,

they’re not adapted to low carbohydrate diets,

that neurons in their brain and body

are using glucose in order to function.

That’s what allows those neurons

to fire electrical potentials.

That’s how we refer to it, firing,

meaning sending electrical signals down their length

to communicate with other neurons.

To illustrate just how important glucose is

for brain function, I’d like to describe a study

that just recently came out

that sits on a long history of similar studies,

but the one that just came out is particularly interesting.

Now, I want to point out that unless I say otherwise,

I’m going to refer to typical diets,

meaning I have to believe that most people out there

are ingesting some starch or carbohydrate.

I do realize there are people

following very low carbohydrate diets

or moderately carbohydrate diets.

I even know that there’s some folks out there

who are on the so-called carnivore diet.

They only eat meat and organs, maybe a little fruit,

but I’m going to assume that the vast majority

of people listening ingest proteins and carbohydrates.

So unless I say ketogenic or I emphasize ketosis itself,

which I will, I’m referring to a kind of typical diet

where people are consuming fats, proteins, and carbohydrates.

I count myself as one such individual.

At some point, I might try the carnivore diet, who knows?

I might try a pure vegan diet, who knows?

But for my entire life up until now, I’m 46 years old,

I’ve been a proud omnivore,

meaning I’ve tried to eat high quality,

as much as I can, unprocessed foods.

I try and really avoid highly processed foods,

but I do eat from those three macronutrient groups,

proteins, carbohydrates, and fats,

and I’m going to assume that most of you do as well.

The study I’d like to emphasize,

recorded from neurons, nerve cells in the brain,

in particular, in the part of the brain

that responds to visual images, a so-called visual cortex,

and neurons in the visual cortex are beautifully tuned,

as we say, to particular features of what we see.

The primary example of this, the kind of classic example,

is if you put a little electrode next to a neuron

in your visual cortex,

or if we put you into an fMRI scanner machine,

which can detect neural activity,

and I were to show you a bunch of just little lines,

you know, bars of light, they could be dark bars of light,

they could be light bars of light

on a screen in front of you,

so some would be vertical, some would be horizontal,

some would be at 45 degrees.

What we would see is that some neurons respond best,

meaning they fire a lot of electrical activity

to vertical lines.

Other ones respond to horizontal lines,

and others respond to 45 degree lines.

And this so-called orientation tuning,

meaning because of the orientation of the line,

is a cardinal classic feature

of the way that your visual system is built.

And everything that you see,

whether it’s a face or a dog or a cat or a landscape,

is built up from these very simple neuron responses.

In other words, when you look at a face,

there are neurons deep in the brain that respond to faces,

but the only reason that those neurons

can respond to those faces

is because they receive signals from neurons

in your visual cortex,

some of which respond to vertical lines,

some of which respond to horizontal lines,

and some which respond to 45 degree lines,

and all of those are built up

in what we call a hierarchical representation,

which is fancy language for it.

Those are the building blocks by which you see a face

and you recognize a face.

And it’s really an amazing phenomenon.

It happens very, very fast.

You never notice that you’re doing this,

but everything is built up

from these fundamental orientation-tuned neurons.

Now, orientation-tuned neurons are so fundamental

that they are the building blocks

by which you make up all other things that you see.

It’s the way you read,

it’s the way that you recognize faces, as I mentioned,

and everything else.

Experimentally, it’s quite straightforward

to measure how sharply tuned one of these neurons is.

In other words, if I were to show you a vertical line

and find a neuron in your brain

that responds to vertical lines,

I could also ask whether or not

that neuron fires any electrical activity

in response to a line that’s not quite vertical,

maybe just 10 degrees off vertical,

or 20 degrees, or 30 degrees.

And what I eventually would find

is that that neuron was orientation-tuned

over a particular range of angles.

It’s not only going to respond to vertical lines,

it’s also going to respond to lines

that are about 10 degrees off vertical in either side,

but probably not much more, maybe 20,

but usually it’s going to be anywhere

from vertical to just tilted slightly, okay?

In the recent experiment

that was published in the journal, Neuron,

cell press journal, excellent journal,

the authors asked a really interesting question.

They asked whether or not the sharpness of tuning,

the precision of orientation tuning of these neurons

is dependent on blood glucose level.

So just to cut to the chase, to give you the answer,

what they found is that when subjects are well-fed,

neurons that responded to vertical

responded very strongly to vertical,

but not very much at all to other angles

of what we call stimuli,

to lines that are 10 degrees or 20 degrees off.

If they looked at neurons that were primarily tuned,

that preferred horizontal lines,

they found the same thing, okay?

So it wasn’t something unique to vertical lines.

What they basically found was the sharpness,

the precision of tuning of neurons in the brain

was best when subjects were fed.

And conversely, when subjects were fasted,

the orientation tuning of these neurons

became much broader.

What it meant was that a neuron

that normally would only respond to vertical

now responded to other angles of lines as well.

You might say, well, that’s great, right?

These neurons that at one point could only do one thing

are now tuned to other things, but it’s not so great

because what that means is that in the fasted state,

your perception of the outside world is actually distorted.

It’s blurred.

It’s not as precise as it is when you’re fed.

And when I say fed, what I really mean

is when glucose is available to neurons.

Now, for some of you, maybe many of you,

and including myself, intermittent fasting

or some variant thereof is actually a state that I like.

It allows me to focus.

For instance, as I mentioned before,

and even earlier in this podcast,

I tend to eat my first meal sometime around 11 a.m.

And then I generally eat my last meal

sometime around 8 p.m., plus or minus an hour on either side.

I’m not super strict about it.

And occasionally I’ll wake up really hungry

and I’ll eat something before 11 a.m.

I’m not super strict about this intermittent fasting thing.

It just seems to be how my appetite works best

given my schedule, et cetera.

In the morning, I tend to be most focused.

And I always associated that with the fact

that I was fasted.

I just water and some caffeine.

About 90 minutes after waking up, I drink my caffeine,

but I hydrate from the time I get up, et cetera, et cetera.

And I know a lot of other people have had the experience

of being fasted and feeling like

they have a lot of mental clarity.

When you are in a fasted state,

typically you’re going to use fuels

that are available to the neurons

based on your intake of food the day before.

Maybe you’re using some glycogen.

Maybe you’re using some fat.

Maybe you’re using some blood sugar

that’s derived from other storage sites in the body.

You don’t actually use fat as a fuel source for neurons

under typical conditions,

but there are ways in which proteins and fats

and glycogen, et cetera,

are converted into fuel that neurons can use.

What’s interesting about this study is that

the study says that when well-fed,

meaning when blood glucose sugar

is at a properly elevated level in the bloodstream,

it can be delivered to the brain in a way

that allows neurons to work best,

which is really all just to underscore

the point that I made earlier,

which is that your nervous system

is extremely metabolically demanding and it loves glucose.

Neurons love glucose.

So the takeaway from this study

is not that you should avoid fasting.

The takeaway from this study

is that there are elements of the fasted state,

in particular, the elevations

and things like epinephrine and norepinephrine,

also called adrenaline and noradrenaline,

that can give us this kind of clarity of mind

that many people are pursuing when they fast.

That’s kind of one of the reasons a lot of people fast.

They like the way that they feel mentally and physically.

But I think it’s only fair to point out

that glucose is the preferred source of fuel for the brain.

And this study that I mentioned

is one of many studies that have explored

how nutritional status or blood glucose status

in the brain and body influence neuronal tuning

and neuronal function.

And it really points to the fact that ultimately,

your brain as an organ is a glucose-consuming machine.

Now, when you eat a food, that food is broken down.

And if it contains carbohydrates,

it’s going to be converted into glucose.

And that glucose can’t get directly

into the brain as a fuel source.

It actually has to be carried across

the so-called blood-brain barrier, the BBB.

And the actual metabolism of glucose

and the delivery of the glucose to the neurons

is carried out by a different cell type.

And it’s a cell type that you should all know about

because it’s the most abundant cell type in your brain

and maybe even in your entire nervous system.

And that’s the so-called astrocyte.

Astrocytes are one of several types of glia.

The word glia means glue,

but many people have taken that name, glia, glue,

to think that, oh, the only thing

that the astrocytes are doing

is just kind of holding things together.

Actually, the astrocytes are involved

in delivering glucose to the neurons.

They are critically involved

in shaping your neuronal function and brain plasticity,

the brain’s ability to change in response to experience.

So these astrocytes are like the little waiters

and waitresses bringing glucose to the neurons,

and the neurons are going to do the heavy lifting

that’s involved in perception and behavior and action.

So if prior to this episode,

you didn’t already realize that glucose, blood sugar,

is vital to the function of your brain

and other neurons of your nervous system, now you know.

And for those of you that have experienced

the increase in mental clarity

that comes after a properly timed, properly composed,

meaning it has the right macronutrients

and the right ratios, and a properly sized meal,

well, then, now you have justification

for eating something as a way

to improve the way that your brain works.

It turns out that your brain is going to work best

when it’s got glucose available.

Whether you like to fast or not,

that’s just the reality of things.

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.

They release a neurotransmitter called acetylcholine,

which causes contraction of the muscle fibers

and allows you to move your limbs.

Those neurons are also very metabolically demanding,

especially when you’re doing demanding types

of physical work, and that could be cycling or running

or weightlifting or yoga or whatever it may be.

Those neurons require a ton of glucose.

If you’ve ever had the experience

of having to think very hard

about how you’re generating a movement

or force yourself to continue to endure in a given exercise,

you might’ve thought, oh, you know, I’m running out of fuel.

That’s why I’m getting tired.

It’s hard to do.

That’s actually the case sometimes,

but that’s not always the case.

One of the reasons that it feels like work

is because your so-called upper motor neurons,

the one that control the lower motor neurons

in your spinal cord, which control your muscles,

they have to be very metabolically active.

It’s one thing to engage in a reflexive movement

where you’re just walking around

or if you’re running continuously,

but when you suddenly have to focus on what you’re doing

and you have to generate specific patterns

of motor movement, well, that feels demanding

because one, it increases the release of adrenaline

in your brain and body, which makes you feel

a little bit agitated and more alert,

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

and hopefully they’re listening to you too,

and you’re really trying to parse what they’re saying

and maybe you’re doing that right now

and you’re trying to really track something,

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.

High fructose corn syrup is approximately 50% fructose,

which turns out to be an enormously high percentage

of anything really, especially when we contrast

that to the concentrations of fructose in fruit.

Fruits have other types of sugars in them as well.

You know, the sucrose content of most fruit

and fruit juices is low,

although there are some fruits like, you know,

melons, peaches, pineapples, and so forth

that contain, you know, a little less than 10% or so

of sucrose.

Things like mangoes can have a lot of sucrose,

but typically the amount of fructose,

fructose, I think is the proper pronunciation

that people are always correcting me,

fructose is anywhere from 1% to about 10%, right?

It’s really going to vary quite a bit.

And many of you have probably heard

of the so-called glycemic index,

which is a basically a measure

of how fast blood sugar rises

after eating particular foods, et cetera.

We’re going to set aside the glycemic index for now,

we will come back to it.

It has some relationship

to the concentrations of fructose in fruit.

But the point that I’d like to make is that fructose

as a sugar is handled very differently

in the body than is glucose.

But I also want to emphasize

that because the percentage of fructose in fruit

is rather low,

especially compared to high fructose corn syrup,

many people have demonized fructose

saying that fructose makes you fat

or that fruit makes you fat.

If you look at the data, that’s not really the case.

The fact of the matter is that the concentrations

of fructose in fruit are so low

that unless someone is consuming a lot of fruit

or they’re consuming a lot of fruit

on the backdrop of a highly processed diet

or a diet that has a lot of other stuff

that they might not want to be ingesting,

you can’t really say that fructose is fattening.

I don’t really think that there’s any basis

for saying that fructose itself is bad.

Now, high fructose corn syrup is a different issue.

And too much consumption of anything,

but fructose included,

whether or not it comes from fruit or otherwise,

can be a problem for the ways that it impacts

the neural circuits that process sugar,

not just glucose, but fructose.

And so we’ll illustrate those neural circuits in a bit,

and it will become very clear to all of you,

regardless of whether or not you have a background

in biology or metabolism, nutrition or otherwise,

why ingesting very high concentrations of fructose

is not going to be a good thing

for the way that your brain functions.

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 ghrelin.

As you recall, ghrelin is a hormone that increases

the longer it’s been since we’ve eaten.

And ghrelin makes us hungry

by stimulating particular neurons in our hypothalamus.

It actually makes us really want to eat.

And in particular,

really makes us want to eat sugary and fatty foods.

Fructose reduces the activity of the hormones

that reduce ghrelin.

And so the net consequence of that

is that fructose increases ghrelin.

So although I, and I think pretty much everyone out there,

save for a few individuals,

agrees that calories in, calories out

is the fundamental principle of weight loss,

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.

Okay?

Now, I also want to be absolutely clear.

This does not mean that eating an apple or eating a melon

or eating a couple of apricots or something

is going to make you hyperphagic.

Meaning it’s going to make you just want to eat

and eat and eat.

That’s simply not the case.

But if you compare fructose and you compare glucose,

not only are they metabolized differently

in the brain and body, but in addition to that,

fructose has this impact of reducing the hormones

that reduce hunger hormones and neural circuits.

And so fructose does have this kind of twist

in its phenotype, right?

Or it’s, I guess if fructose had a dating profile,

this would be a kind of a red flag in that profile

because fructose itself,

while it’s actually a pretty good fuel source in many ways,

and it’s often packaged in things like fruits,

which bring along fiber and vitamins and minerals

that I think for many of us are things

that we should be eating more of and ingesting more of,

it can suppress the pathways that suppress hunger.

And as a consequence, it can increase hunger.

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.

But even from fruit, some people will find

that fruit really quenches their appetite.

Other people will find that fruit stimulates their appetite.

And I suppose if you’re trying to stimulate your appetite,

then ingesting more fruit

might actually be advantageous to you.

So fructose provides a bridge for us

between a particular kind of sugar, hormone function,

in this case, ghrelin, 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 very high level

actually is not just related to the taste

of the foods that produce that elevation

in glucose, sucrose, 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.

And actually, at this point,

I should probably give a confession.

I’ve said today, and I’ll say it again,

and I’ve said it on previous podcasts,

I don’t have much of a sweet tooth,

and indeed that’s true.

And I can kind of pass on chocolate or ice cream

or things like that.

It seems like with each successive year,

sweet things are less and less appealing to me.

Of course, savory foods,

anything that is really fatty, salty, savory,

those don’t last long in my presence.

But I always say I don’t really like sweet things so much,

and I don’t, I like sweet people,

but I don’t tend to like sweet foods, which is true.

But there’s probably one exception, and that’s mangoes.

And it turns out that mangoes have the highest percentage

of sugar in them, in particular fructose,

as well as other forms of sugars.

So what I do, because I love mangoes so much,

is I will have mangoes probably twice a week,

but I’ll have them after some sort of resistance training

or hard run or something like that.

Because it is the case that after you exercise hard,

in particular, exercise that is of the high intensity

variety, that your body is more efficient

at using circulating blood sugar.

It’s able to store that or use that for fuel.

And so what I’ll typically do is just take the mango,

actually eat the peels too.

I know that probably some people are going to cringe

when they hear that.

I find them delicious,

so I’ll just bite into those things like apples.

I don’t eat the pits, however.

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, et cetera,

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,

and this is a common theme throughout the nervous system,

and that’s parallel pathways.

Parallel pathways are the ways

that you can distinguish light from dark.

Parallel pathways are the ways that you can distinguish

high-pitched sounds from low-pitched sounds.

Parallel pathways are the ways that you can

flex your muscles versus extend your muscles.

For instance, if you move your wrist closer to your shoulder,

you’re flexing your bicep and you’re actually inhibiting,

you’re actually preventing the action of your tricep.

If you move your wrist away from your shoulder,

you are essentially using your extensor, your tricep,

and you’re inhibiting the activity of your bicep.

So for every function in your body

that you might think is controlled by one brain area

or one neural circuit, almost always there are two

or more so-called parallel pathways that ensure

that that particular behavior happens.

Now, 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 nutritive 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

that even exists in fruit flies, hence fruit fly.

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 nutritive 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.

And I mentioned, of course,

that fructose may actually work directly on the brain.

That’s still unclear for humans.

You know, the jury’s still out on that.

We will see.

But 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 nutritive components that arrive with that taste.

And simply by understanding that can allow you

to circumvent some of the sugar cravings

that you might otherwise be a complete hopeless victim to.

Also in this episode, I will talk about ways

that you can sort of undermine or short-circuit

these circuits, if you will,

in order to reduce sugar cravings on a regular basis,

if that’s your goal.

Okay, two parallel pathways.

One of the parallel pathways

has to do with conscious perception.

So animals of all kinds, mice, rats, and humans

will prefer sugary tastes to non-sugary tastes.

When we eat something that tastes sweet,

we register that sweet taste by way of sweet receptors,

literally little ports or portals of neurons

on our tongue and on our palate.

A lot of people don’t realize this,

but there are a lot of taste receptors on the soft palate

and around the mouth, on the sides of the mouth.

So you’re actually tasting things, not just with your tongue

but with your entire mouth and your palate.

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.

In fact, there are beautiful neuroimaging studies

that show that when people ingest a sugary drink,

their perception of images of foods change very much

to make those foods appear more appetizing

and not just foods that contain sugar.

Results of those studies do show

that there’s an increase, for instance,

in the perception of detail and images of ice cream

after you ingest a sweet drink

or even put like a hard candy into your mouth.

It will make you seek out sugary things more.

It will make sugary things look more appetizing

but also other foods more appetizing.

So I think it’s important that people recognize that fact

that when you have a sweet taste in your mouth

or when you’ve tasted something sweet within your mouth,

I should say, your perception of food

has immediately shifted.

These are fast neural pathways,

and we’ll get into some of the brain structures

in a moment, but these are fast neural pathways

that shift your entire self

toward seeking more sugary stuff and more food generally.

Now, 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 fix

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 neuromodulator dopamine.

Dopamine is a molecule that is released

from several places in the brain.

There’s a so-called mesolimbic 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.

That makes perfect sense.

Why would you have a brain area involved in motivation

if you couldn’t actually do something with that motivation?

So the way that your brain is designed

is when there’s an increase in dopamine

in the mesolimbic reward pathway,

there are signals sent to an area of the brain

called the striatum.

We’re going to spend a little bit of time today

in the striatum.

It’s got a dorsal part, meaning an upper part

and a ventral part, which means a lower part.

And the dopamine sent to those areas places us,

excuse me, into modes of action to pursue particular things.

Sugar or sweet tastes, I should say to be more specific,

have an incredibly potent ability

to activate dopamine release

within the mesolimbic reward pathway.

This has been shown over and over and over again.

In animal models and in humans.

This is especially true, I should mention,

through the ingestion of sweet liquids.

Now, this becomes a very important point to us

a little later on when we talk about the proliferation

of sodas and sweet drinks,

and dare I even say non-sugar or diet sodas.

We’re going to get into that a little bit later.

Perhaps one of the most third rail topics in nutrition.

But when we ingest something sweet,

the perception of that sweet taste increases dopamine

in the mesolimbic 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.

Again, for those of you that are very disciplined,

you can probably eat that one piece of chocolate

and be just fine.

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.

As described in the episode that I hosted

with my phenomenal colleague

from Stanford School of Medicine, Dr. Anna Lemke,

she’s an expert on addiction and dopamine pathways.

The dopamine circuits of the brain

have what we call a pleasure pain balance.

And there I’m paraphrasing what Dr. Anna Lemke has said

and has written about in her beautiful book,

“‘Dopamine Nation.”

If you haven’t read that book, I highly recommend it.

Whether or not you have issues with addiction

or you know people that do or you don’t,

it’s an incredibly important read,

especially if you’re interested in understanding

motivated behaviors and ways to channel your behaviors

in life toward healthy motivated behaviors

and make sure that you avoid some of the common pitfalls

that people fall into, not just addiction,

but things like overuse of social media

or wasting time in general.

It’s a phenomenal book.

In that book, and of course, within research articles,

you will find evidence of this so-called pleasure pain

balance that exists within our dopamine circuits.

Nobody has dopamine circuits that allow them to escape

this pleasure pain balance.

And the way this works is that anytime that we engage

in a behavior or we ingest something

that increases our levels of dopamine,

there is a subsequent increase in the neural circuits

that control our sense of frustration, pain, and lack.

And you can actually notice this phenomenon.

If, for instance, you’re somebody who really likes chocolate

or you really like something else,

pay attention to the way that you experience indulging

in that thing.

If you eat that piece of chocolate

and you really focus on savoring its amazing taste,

you’ll notice that it provides some quenching

of your desire for, let’s say, sweet stuff

or chocolate or both.

But right as you stop experiencing that,

right as that chocolate intake tapers off,

as you swallow it down your throat,

or you just pause for a second afterwards,

what you’ll notice is that your brain and body

actually orient toward wanting more.

And that wanting of more is really the action

of the neural circuits that underlie pain

and are pushing your dopamine levels back down.

And when these circuits go awry, or I should say,

when people fail to control themselves

within the context of that pleasure-pain balance,

the typical behavior is to reach for yet another chocolate

or to then look for something that will quench that desire

and get dopamine levels back up.

Now, the way these pleasure-pain circuits work

is very diabolical because it turns out

that were you to take another piece of chocolate,

yes, your dopamine levels would go back up,

but not to the same extent

that they did the first bite of chocolate that you had.

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.

And the greater the dopamine increase,

the greater the subsequent action of those pain circuits.

So this puts you on a very complicated seesaw.

It’s a very wobbly, precarious state to be in,

which is not to say you shouldn’t have a piece of chocolate.

It’s just to say that the sweet taste of sweet things,

in particular things that we crave very much

and we wait and wait and wait,

and then we allow ourselves to indulge,

those trigger changes in our neurochemistry

and our neural circuits

that place us in a very vulnerable place

to either want more and more of that thing

or to seek out other ways to fill

that kind of emptiness that we feel or that gap,

like, oh, I would love more,

but I’m not going to allow myself more.

Now, again, I’m not saying

that you shouldn’t pursue pleasurable things.

I mean, this molecule dopamine exists for a reason.

It’s the, frankly,

because of its involvement in sex and reproduction,

it’s the reason we’re all here in the first place,

because last time I checked,

the only way any of us got here was one way or another,

sperm met egg, and there was conception.

I still believe there are no exceptions to that

that I’m aware of anyways.

That is a process where I should say

the events leading up to that process

typically involve dopamine in one way or another.

There are exceptions to that too, but you get the idea.

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.

Okay, so when you ingest something sweet,

you perceive that sweet taste,

and a cascade ensues within your brain

that makes you want more of the sweet thing.

That’s the conscious pathway for sugar perception,

for sweet perception.

Now there’s the second pathway.

The second pathway is what’s called

the post-ingestive reinforcing properties of sugar,

which is really just a fancy nerd speak way of saying

there are events that happen 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.

In order to illustrate the immense power

of these subconscious circuits for sugar seeking,

I’d like to describe an experiment.

And this is just one experiment of many,

of dozens or more experiments done in animal models

and humans, which essentially illustrate the same thing.

And as I describe this experiment,

I think you will come to understand

the power of these circuits.

I’ll provide a link to this study in the caption.

The first author is Freeman.

The paper was published in Frontiers in Bioscience,

but there have been others, papers in Nature Neuroscience,

papers in Neuron, Cell Press Journals, et cetera.

Many, many journals, many, many papers.

If subjects are given the choice of drinking plain water

or a sweet tasting fluid,

their preference for the sweet tasting fluid

is much, much higher, right?

Sweet things taste better than plain water,

at least for most people and certainly for animals.

Now, if for instance, you take an animal

which completely lacks sweet receptors,

and you can do this through some molecular genetic tools

and gymnastics in the laboratory,

we call these knockout mice,

where you can knock out a particular receptor

for sweet taste, you can confirm

that there’s no perception of sweet things

or at least no preference for sweet things

in those animals.

In humans, you can numb the mouth.

There are other pharmacologic ways

that you can eliminate sweet receptors in the mouth.

And by doing that, people will tell you,

no, I can’t taste anything sweet.

It’s just, you could give them ice cream,

you could give them pure sucrose,

you give them table sugar,

and they wouldn’t be able to perceive it as sweet.

If you eliminate the perception of sweet taste in the mouth

and you offer people or laboratory animals

water versus some sugar-containing solution,

you eliminate the preference for the sugary solution,

which tells us that the perception of sweet

is important for the preference for sweet-tasting drink.

This is also true for sweet-tasting foods,

I should mention.

However, in both animal models and in humans,

after about 15 minutes,

subjects start preferring the sugary water,

even though they can’t taste that it is sweeter.

Okay, so to repeat that,

if you eliminate the ability to sense sweet,

to perceive sweetness in foods,

then you eliminate the preference for sweet beverages

or sweet foods.

So that’s not surprising.

But if you wait about 15 minutes,

the preference for the sweet beverage

or the sweet food comes back.

Now that doesn’t mean that they can perceive the sweetness.

In fact, the way these experiments are done is very clever.

You offer people various cups of different things

or different food items,

and then you just look at what they eat more of

or what they prefer to eat more of.

So this experiment is so crucial because what it says

is that the preference for sugar-containing foods

is in part due to the sweetness of those foods,

but in part due to something else.

And this something else

is what we call the post-ingestive effect.

And as I mentioned before, it took about 15 minutes,

and you’ve actually experienced this,

whether you realize it or not,

this phenomenon of post-ingestive rewarding properties

of sweet foods, meaning what happens in your body

when you ingest something

that increases your blood glucose very much

has no doubt controlled you

from the inside below your awareness.

This was happening to you and you didn’t realize it.

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 Borges at Duke University.

And these cells respond to, among other things,

to the presence of sugar within the gut.

So when we ingest a sugary food or drink,

or we ingest a food or drink

that simply contains fructose, sucrose, glucose,

or some other form of sugar

that later, through metabolism,

will be converted into glucose,

the neuropod cells are able to register the presence

of those sweet or glucose-stimulating foods.

And in response to that, send electrical signals,

because electrical signals

are the way neurons communicate,

up to the brain via the so-called vagus nerve,

the vagus nerve, of course, being a nerve pathway

famous for its role in relaxation.

That’s kind of the assumption out there

that it’s always involved in relaxation.

That’s not the case.

It’s involved in a lot of things besides relaxation.

But nonetheless, these neuropod cells

send electrical signals through a particular highway

within the vagus to the so-called nodose ganglion.

This is a cluster, a ganglion is just a cluster of neurons.

And then the nodose ganglion sends on information

to the nucleus of the solitary tract.

The nucleus of the solitary tract is an area of the brain

that we’re going to talk about extensively today.

It’s very important for understanding sugar preference.

These neuropod cells also trigger activation

of dopamine pathways within the mesolimbic reward pathway.

In other words, there are signals conveyed from the gut,

meaning stomach and intestines, to the brain

anytime we ingest sweet foods,

but it has nothing to do with our perception

of them being sweet.

It has everything to do with the fact that sweetness

of food is almost always correlated with an ability

to increase blood glucose.

And the net effect of this is a parallel pathway

by which dopamine is increased further.

Now, the experiment that I described before

of animals or humans ingesting something

that contains sugar,

but not being able to perceive its sweetness.

And yet after a period of time,

still preferring that food or drink

to non-sugar-containing food or drinks,

even though they can’t distinguish their tastes,

is dependent on these neuropod cells and related pathways.

What this means for you

is that anytime you eat something sweet,

that substance is actually causing your gut,

your stomach and your intestine,

or to be more precise, I should say,

that food substance is causing the neuropod cells

in your stomach and intestines

to send a parallel set of signals up to your brain

saying, eat more of that, or simply eat more,

eat more, eat more, and preferably eat more sweet foods.

So we’ve all heard of hidden sugars,

meaning the sugars that manufacturers have put into foods

and disguised them with other flavors.

I talked about this in the episode on salt,

using salt to mask the taste of sweetness

so that people ingest more sugar.

That is not an accident that hidden sugars

are often hidden with salt or with other flavors.

It’s done so that people will, meaning you or me,

will want to ingest more of a particular food

independent of how sweet that food tastes.

And in fact, some crackers, for instance,

chips, for instance, you might think,

oh, well, you know, chips, they’re not sweet,

they’re salty and savory.

And again, I’ll mention I love salty, savory foods,

including certain foods.

I love kettle chips, for instance.

I try not to walk by them in the grocery store.

I usually have to eat one bag while I’m in the store

and then another later.

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 in concert with the fact

that we have this dopamine-pain-pleasure balance,

excuse me, that I referred to earlier,

you start to realize that there are multiple mechanisms

that are 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, if it doesn’t already seem diabolical enough

that sweet things that we perceive as sweet

make us want to eat more of those because of dopamine,

and then send us down this pain-pleasure pathway

that I mentioned earlier,

and the fact that we have this subconscious circuit

coming from the neuropod cells in our gut

that are registering the presence of sugar

or glucose-increasing foods in our gut

and sending those signals to the brain

for yet more dopamine-pain-pleasure challenges,

there’s a third layer to this whole thing.

And that has to do with how sugar is metabolized

in the brain, or I should say how glucose is used.

Without getting into too much detail,

some of the more beautiful studies of neuroimaging

and evaluating which brain areas are active

when we eat certain foods

were done by Dr. Dana Small’s lab at Yale University,

and in some of her previous work when she was elsewhere,

and of course, by other laboratories too.

And they used an approach

called positron emission tomography,

and they and others have used PET scanning,

as it’s called, positron emission tomography,

along with a tool called 2-deoxyglucose.

2-deoxyglucose is actually involved in the procedure

of seeing which brain areas are active

when people eat foods

or engage in other types of behaviors.

But the way that 2-deoxyglucose, sometimes shortened 2DG,

the way that it works

is to block glucose uptake from neurons

and instead bring along with it a marker

that one can see through imaging.

So in other words,

a tool for looking at what parts of the brain are active

when eating particular foods

actually prevents foods such as sugar

from allowing glucose to get into particular neurons.

Now, that might seem like a bad situation.

You’d say, well, wait,

you’re trying to understand how sugar works in the brain,

and then you block the ability for sugar glucose

to bind to or be used by these neurons

because of the thing that you’re using for the experiment.

Exactly, it’s a huge problem,

but it turns out to be a huge problem

that led to a great insight.

And the great insight is this,

the preference for sweet tasting foods and liquids

is actually blocked by 2-deoxyglucose.

What that means experimentally,

but also in terms of what it means for you and me

in the real world

is that there’s yet a third parallel pathway

that’s related to the use of blood sugar,

the use of glucose by neurons

that further reinforces our desire to eat more sweet things.

And the preference for sweet foods

can actually be eliminated through 2-deoxyglucose.

Now, I definitely don’t want people going out

and consuming 2-deoxyglucose.

This is a laboratory tool.

It is not something that you should be ingesting.

So don’t go look it up and try and get some.

There might be other uses for it, but that’s not the point.

The point is that it is the sweet taste of sugary foods.

It is the signals coming from your gut,

from your digestive tract to your brain.

And it’s the use of the metabolic consequences

of sugary foods that are acting as a three-pronged push

on your desire to consume more sugary foods.

So this car analogy that I used before

where it’s some weird car that has two accelerators,

it actually has three accelerators.

And so with three accelerators, all pushing the system hard,

we can say, wow, there must be something really special

about this pathway.

And indeed there is.

This pathway is the quickest source of fuel for the brain

and the rest of the nervous system.

It’s the preferred source of fuel

for the brain and nervous system.

And I realize as I say that all the ketonistas

are probably going, no,

actually ketones are the preferred source.

Okay, I acknowledge that.

There are conditions under which

you can bring your blood glucose very low,

and there are reasons to do that.

Actually, ketosis has been a terrifically successful

treatment for a lot of forms of epilepsy,

in particular pediatric epilepsy.

Many people do derive benefit from ketogenic diet.

So I’m not knocking ketogenic diets.

But if you were to look at what neurons normally prefer,

meaning in a typical diet regimen, it would be glucose.

And the fact that fructose

is eventually converted to glucose.

The fact that when we ingest sucrose,

it’s eventually converted into a fuel that neurons can use.

That’s very much in the glucose pathway.

What you basically arrive at is the fact

that your nervous system is a glucose-consuming machine,

and you’ve got at least three pathways,

of which I’ve described,

that are pushing on your brain consciously

and subconsciously to get you to seek

and consume more sugar.

Now that all sounds like a pretty depressing picture,

at least for those of you that are trying

to reduce your sugar intake.

And of course we can all reduce sugar intake

by way of sheer will.

We can not have those foods at home.

We can restrict ourselves from those.

But there are some things that we all can

and perhaps should do in order to regulate these pathways

such that we don’t feel so controlled by them,

but rather that we control their output.

And of course they are us and we are them.

So this gets into all sorts of issues of consciousness

and free will that I certainly don’t want to cover

in this episode.

But nonetheless, I think once you understand

that these circuits exist and you understand

that there are simple substitutions and modifications

that one can make to their food intake

that can work within these pathways

and even bypass some of these pathways,

you start to realize that you have a lot more control

over sugar intake and sugar appetite

than you previously thought.

Now, many of you have heard of the so-called glycemic index.

The glycemic index is a measure

of how quickly blood sugar rises

after 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 short circuit 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.

And this is why there are some seemingly paradoxical aspects

to sweet stuff in terms of the 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, right?

So the glycemic index is not something to hold wholly

in most cases,

because most people are not ingesting foods in isolation.

And there’s actually a lot of argument

as to whether or not the glycemic index

is really as vital as some people claim.

There’s also the context

in which you ingest particular foods.

As I mentioned earlier,

after I do hard training of any kind,

meaning training that ought to deplete glycogen,

so hard resistance training,

I actually make it a point to ingest

some very sweet high glycemic foods like a mango.

I’ll also ingest some starches

because I’m trying to replenish glycogen.

I’m also trying to spike my blood sugar a little bit

because that can be advantageous

in terms of certain strength

and hypertrophy protocols, et cetera.

But most of the time I’m avoiding these high glycemic foods

and high sugar foods.

I should point that out.

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.

So if we think about the analogy of three accelerators,

meaning three parallel neural circuits,

all essentially there to get us to seek out

and consume more sweet tasting and sugary foods,

well, then the glycemic index

is sort of our measurement of how hard we are pushing down

or how fast we are pushing down on those three accelerators.

And so 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 short circuit some of the dopamine release

that’s caused by ingesting sugary foods,

it can be advantageous to ingest sweet foods

either alone or 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 steeper 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.

You might think, well, why would I want to do that?

I want the maximum dopamine output

in response to a given sweet food.

I don’t just want the level 10,

I want the level 100 output of dopamine,

but you really don’t

because of the pleasure pain balance that dopamine causes.

And in fact, if we consider some of the non-food substances

that really push hard on these dopamine pathways,

we can come up with a somewhat sinister,

but nonetheless appropriate analogy.

The drug cocaine causes very robust,

potent increases in dopamine within the brain,

and typically causes people to want to ingest more cocaine

because of those sharp increases in dopamine.

But within the category of the drug cocaine,

there are various modes of ingestion.

Some people inhale it,

some people will inject it intravenously,

some people will smoke it.

And those different forms of taking cocaine

actually impact the dopamine circuits differently.

And it turns out that crack cocaine,

the smokable form of cocaine rock,

increases dopamine to a very high degree,

but also very, very quickly.

And it is the sharp rise in dopamine over time,

not so much the absolute level of dopamine

that makes crack cocaine so absolutely addictive.

So sometimes you’ll hear, you know, sugar is like crack.

Well, that’s getting a little extreme

because even though I don’t think the measurements

have been done in the same experiment,

I think it’s reasonable to think

that the absolute level of dopamine

caused by ingesting sugar, at least for most people,

is not going to be as high as the absolute level

of dopamine caused by smoking crack.

Of course, it goes without saying,

please don’t do cocaine in any form, by the way.

It is appropriate to say

that the rate of dopamine increase over time

has a profound effect on how people will,

and if people will, go on to want to pursue more

of what caused that increase in dopamine.

So what I’m basically saying is,

if you’re going to ingest sweet foods

in order to satisfy a sweet craving,

ingesting sweet foods for which the glycemic index is lower

or in which you’ve adjusted those glycemic index foods

through the co-ingestion of fiber or maybe fat

might be beneficial.

So is this justification for putting peanut butter

on that piece of chocolate

or for having a bowl of ice cream

along with the mango that you’re craving?

In some sense, yes.

However, there’s also the issue of how sweet

and how delicious something tastes.

Highly palatable foods, absolutely delicious foods

trigger that one neural circuit,

that one accelerator that we’re talking about

in terms of our analogy of three accelerators.

And the more delicious something tastes within our mouth,

the further increase in dopamine.

So if you really wanted to adjust your sugar cravings

and you really still want to ingest some sugary foods,

you probably would be better off combining fiber

with that sugary or sweet food.

Now, I do realize that it’s somewhat unusual

and you probably get some strange stares

if you decided to consume broccoli, for instance,

along with your chocolate or with another dessert

that would otherwise cause a steep increase in blood sugar

and has a high glycemic index.

But nonetheless, if your goal

is to blunt your sugar cravings,

what you really need to do is blunt that dopamine increase.

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-ingestive 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.

Certainly there are exceptions to that,

but I think the bulk of data point to the fact

that ingesting these highly palatable,

certainly highly palatable, highly processed foods

or foods that contain a lot of high fructose corn syrup

can be really deleterious to our health, especially in kids.

And I’m not going to cite off a bunch of statistics.

You’ve all heard them before that, you know,

for hundreds of years, we ingested, you know,

the equivalent of a few cups or pounds of sugar per year.

And, you know, now people are ingesting hundreds of pounds

of sugar per year.

The major culprit always seems to be sugary drinks,

meaning soft drinks, and I think indeed that’s the case.

I do want to point out the incredible work

of Dr. Robert Lustig, who’s a pediatric endocrinologist

at University of California, San Francisco,

who was really early in the game of voicing the dangers

of so-called hidden sugars and highly processed foods.

There are other people, of course, now talking about this.

His laboratory has done important work showing,

for instance, that if high fructose corn syrup

or even just fructose is replaced with glucose,

even if the same number of calories is ingested,

that there are important, meaning significant reductions

in type two diabetes,

some of the metabolic syndromes associated

with high fructose corn syrup and on and on and on.

And of course there are other culprits in type two diabetes.

There are other factors that are going to lead to obesity,

but I think the work from Lustig and others

has really illustrated that we should all be trying

to reduce our intake of highly refined sugars

and high fructose corn syrup,

and certainly trying to reduce our intake

of very sugary drinks, not just soft drinks,

but also fruit juices that contain a lot of sugar.

Now, even for people that are of healthy weight

and who don’t have metabolic syndromes,

there may be an additional reason to not want

to ingest very sweet foods and highly refined sugars.

And this has to do with a new and emerging area

of nutrition neuroscience.

And I want to point out that these are new data, right?

So it’s not a lock.

The double blind placebo controlled studies

in large populations have not been finished.

So I want to make sure that that’s clear,

but I also want to make clear

what some of the really exciting data

coming from Dana Small’s lab at Yale

and from other laboratories are showing.

And this has to do with what’s called

conditioned taste preference.

Using a kind of Pavlovian paradigm,

what they do is they have people,

and these studies were done in people,

ingest maltodextrin, which increases blood glucose.

Doesn’t have much flavor,

but even if it does have a little bit of subtle flavor,

the maltodextrin is cloaked by some other flavor.

And by cloaking it with that other flavor

or pairing it with that other flavor,

what they find is that over time,

because the maltodextrin increases blood glucose

and they are ingesting a particular flavor

along with that maltodextrin,

they can then remove the maltodextrin

and the flavor will induce an increase in insulin.

The increase in insulin, of course,

is the consequence of the fact

that anytime there’s a rise in blood glucose,

provided the person isn’t diabetic,

there’s a parallel increase in insulin.

Now, this is very interesting because what it says is,

well, at a first pass, it says that we are very Pavlovian

in terms of our physiological responses to foods

and particular flavors come to be associated

with particular patterns of blood glucose increase

and hence patterns of insulin increase

because of course insulin manages glucose

in the bloodstream, as I mentioned earlier.

This also has implications for understanding

things like artificial sweeteners.

And here, I want to highlight

that this is still very controversial work,

needs more data, but nonetheless,

I’d like to share it with you for consideration.

The small laboratory has done studies in humans,

both in adults and in children,

showing that if the flavor of artificial sweeteners

is paired with maltodextrin

and then the maltodextrin is removed,

that the artificial sweetener taste itself

can subsequently increase insulin in the bloodstream.

In other words, taking something that increases blood sugar,

attaching a flavor experience to that,

having children or adults ingest that thing

allows the nervous system to associate that flavor

with that increase in blood glucose,

but then you can remove the glucose increasing substance

and the flavor alone will increase insulin

because insulin typically follows blood glucose.

So this is a conditioning effect.

Now, the reason these data are controversial

is several fold.

First of all, the landscape around the discussion

around artificial sweeteners

is definitely what I would call a barbed wire topic.

And I want to preface what I’m about to say next

by saying I actually ingest artificial sweeteners.

I will have the occasional diet soda, not every day,

maybe, I don’t know, once or twice a month.

I don’t particularly like the taste,

but I’ll do it just because it’s around

and I want some caffeine and I like the carbonation

if I’m on a plane or something.

I do ingest plant-based non-caloric sweeteners.

To my knowledge, there have not been high quality studies

of plant-based non-caloric sweeteners

in the context that I’m referring to here, okay?

Nonetheless, these studies show that particular flavors

can be conditioned to cause an insulin increase

and the flavor associated with certain

artificial sweeteners is included in that category

of flavors that can induce insulin,

even in the absence of something

that can increase blood glucose.

Now, the simple takeaway from these studies

would be the following.

And this is actually the one interpretation

that Dana Small has offered to her data,

but she offers other interpretations as well.

One interpretation is that if people are going to ingest

artificial sweeteners and they do that along with foods

that very sharply increase blood glucose,

then there is the potential, highlight the potential,

for those same artificial sweeteners to increase insulin

even in the absence of food.

In other words, let’s just draw the scenario out

in the real world.

You’re having a diet soda

along with a cheeseburger and fries.

You do that every day for lunch, okay?

This somewhat extreme example, but natural world example.

You do that every day for lunch,

and then you just have a diet soda alone.

The extreme interpretation of the data

that they’ve collected says, well,

that diet soda alone will increase insulin,

even though there’s no increase in blood glucose

because you haven’t ingested food with it

because you conditioned that taste of artificial sweetener

to the experience of a rise in glucose and hence insulin.

Now, the counter argument to this would be,

well, that’s a very unusual situation.

Maltodextrin causes big increases in blood glucose,

so that’s not really a fair experiment

or it’s not a natural world experiment.

And I think that’s a decent assessment,

although I will point out that one of the reasons

why this study is so controversial

or why these data are so controversial

is that the experiment actually had to be stopped,

and particularly the experiment in children

had to be stopped because the changes in insulin

that were observed early in the study were so detrimental

that the institutional review board quite appropriately said

we can’t do this to these kids.

They’re experiencing these odd shifts in insulin

that are not healthy for them

when they’re just ingesting artificial sweeteners

in the absence of these glucose increasing foods.

So once again, I do ingest artificial sweeteners.

I’m not saying that they are dangerous.

I’m not saying that they are not dangerous.

I’m saying that you have to decide for yourself.

In previous episodes, I’ve highlighted

that artificial sweeteners have been shown

in studies of animals that when given in very high doses,

sucralose in particular,

there can be fairly robust disruption to the gut microbiome,

which is vital for immune health

and brain health, et cetera, et cetera.

But thus far, our knowledge

of how artificial sweeteners negatively impacts

or positively impacts, I should say,

the microbiome and other deleterious effects

on the body has mainly been explored in animal studies.

Again, the work by Dana Small has been done in humans.

There’s some parallel work by others in animal models.

I bring it up today to illustrate the following point.

Normally we have a pathway

that we don’t have to condition at all.

It’s there from birth whereby ingestion of sweet foods

causes increases in dopamine.

And there are parallel pathways by which neurons in our gut

and elsewhere in our body trigger further increases

in dopamine.

So there’s no need for a conditioned response

or to become Pavlovian about this, right?

You’re hardwired to want to eat sweet things

by at least two and probably three parallel pathways.

Now, the work from Dana Small’s lab and others

that have illustrated this conditioned flavor preference,

I think beautifully show that any flavor that’s associated

with a glucose spike or a long sustained increase

in glucose can also be conditioned.

In other words, the circuits for dopamine

that reinforce the desire to eat particular things

is not unique to the sugar pathway.

And this is one of the reasons I believe

why ingestion of sweet foods doesn’t just lead us

to want to eat more sweet foods.

I think that is absolutely clear based on animal data

and on human data.

I think that’s robust.

It’s actually the stuff of textbooks now.

But in addition, ingesting sweet foods and or foods

that raise blood glucose,

but that we don’t perceive as sweet.

So for instance, foods with hidden sugars,

sugars that have been masked by salty or spicy tastes,

increases our desire for glucose elevating foods

and food generally.

I think that’s the only logical interpretation

of the data that I can arrive at.

So for people that struggle with regulating their appetite

or with regulating their sugar appetite,

I think the understanding of conditioned flavor preference

while a little bit complicated ought to be useful

in trying to navigate reducing sugar cravings

and sugar intake.

As a segue into tools to control sugar intake

as a means to both regulate sugar intake itself

as well as food intake overall

and steer us towards healthier choices.

I’d like to talk about some of the special populations

out there that might want to be especially wary

of having a dysregulated sugar appetite system.

And the group I’m referring to specifically

are those with attention deficit hyperactivity disorder,

or I should say, and or people who have issues

with focus and attention generally.

And I think more and more nowadays,

I’m hearing that people are having a hard time focusing.

This probably has something to do with our interactions

with electronic devices.

As I always say, if a picture is worth a thousand words,

a movie is worth a million pictures.

And the fact that we can access so many movies

just by scrolling with our thumb

is something that the nervous system

has just never contended with before in human history.

I’m confident of that.

And it’s not that it can’t deal with it.

The question is, what’s the trade-off?

You know, what are the consequences of that?

So attention and ability to focus is obviously key

to success in school, success in relationships,

success in the workplace and success in life.

We could probably even go so far as to say

one’s ability to succeed in anything

is proportional to one’s ability to focus

and then deliberately defocus

when the time comes to defocus, right?

Because we all need rest and we need to disengage

and then re-engage.

If you look at the sum total of the meta-analyses

and the clinical data on ADHD and nutrition,

you arrive at a pretty clear answer,

which is that sugar consumption,

in particular highly refined sugars,

is just not good for people with ADHD

or with attentional issues.

Now, as I say that, I also want you to recall

the earlier study that I referred to

whereby the tuning of neurons in the brain

is highly dependent on glucose.

So this doesn’t mean consuming no glucose

is going to be a good idea.

It doesn’t mean that the ketogenic diet

is necessarily the best diet for ADHD,

although there are some people pursuing that

and exploring that and we’ll do yet another episode

on ADHD at some point that goes a little bit deeper

into that because there’s some new data.

I did do a very long and fairly extensive episode on ADHD.

You’re welcome to look that up if you like in our archive,

excuse me, in our archive at hubermanlab.com.

It’s all timestamped.

So, you know, because a number of people said,

oh, you know, it’s an episode on ADHD

and you made it two and a half hours long.

Yes, we did because we wanted it to be as comprehensive

as we could at the time, but it is timestamped.

So you can just jump to the particular topics of interest

in their short little cassettes there.

Now, if you’d like to know upon what I’m basing

this statement that sugar consumption

and highly refined sugar consumption

is potentially bad for ADHD,

basing this mainly on the conclusions

of a really nice paper that the title of the paper

is Sugar Consumption, Sugar-Sweetened Beverages

and Attention Deficit Hyperactivity Disorder,

A Systematic Review and Meta-Analysis.

And this is a paper,

we’ll put a link to this in the caption.

This was published in Complementary Therapies in Medicine,

which is a bit of an atypical journal in some sense,

but I really like this meta-analysis.

The sum total of this meta-analysis is really that

when especially kids get beyond four sugary drinks per week,

so four sodas of, you know, typical 12 ounce soda,

when they get past four 12 ounce sugary sodas,

they didn’t, as far as I know,

look at artificial sweetened sodas.

That’s when you start to see a shift

towards more negative outcomes,

more symptoms of existing ADHD.

Now, where the controversy comes in is whether or not

sugar consumption can actually trigger or cause ADHD.

And I don’t think we can conclude that at all at this time.

And this review, if you decide to check it out,

review slash meta-analysis, I should say,

if you decide to check it out,

goes into some of the nuance around that.

What’s also interesting in terms of ADHD and sugar intake,

and probably has relevance to all of us,

is that they also cover some of the interesting data

showing that supplementation with omega-3 fatty acids

can actually be beneficial for people,

in particular, kids with ADHD.

I’ve talked before about the utility of omega-3s

that’s been shown in various studies

that have compared omega-3 fatty acid intake

to, say, prescription antidepressants like SSRIs,

like Prozac, Zoloft, and similar, fluoxetine.

And the results of those studies are pretty clear,

at least to me, that provided that one gets

at least one gram of EPA, essential fatty acid,

so it’s not just getting one gram per day,

but one or more grams per day

of the EPA form of essential fatty acid,

can rival some prescription antidepressants

and or decrease the amount of antidepressants

that’s required to take,

which for a lot of people can be a very useful thing

because of the side effect profile

of many of those antidepressants.

Of course, talk to your psychiatrist, talk to your doctor,

but the omega-3s are no doubt powerful.

And then, of course, there’s a whole story

about omega-3s in heart health.

And of course, like anything else,

there’s some controversy around omega-3s,

but I think the data are clear enough to me

around mood and cardiovascular health

that certainly I personally ingest them.

But as always, I always say,

anytime you’re going to add or remove anything

from your nutrition, supplementation, exercise,

or otherwise your lifestyle,

definitely consult with a board-certified physician.

I don’t just say that to protect me,

I say that to protect you.

You are responsible for your health ultimately.

So omega-3 supplementation has been shown

to be beneficial for ADHD.

Why am I talking about this in the context of an episode

on sugar and the nervous system?

Well, if you remember those neuropod cells,

those cells in your gut that respond to sugar

and send signals up to the brain

to cause the release of dopamine,

well, it turns out that neuropod cells

also respond to amino acids and to fatty acids,

in particular, essential fatty acids.

So these cells that we call neuropod cells

have three jobs.

One is to detect levels of sugar in the gut.

The other is to detect levels of amino acids

and to detect levels of particular essential fatty acids

and communicate that information to the brain.

And I should point out,

when I say communicate that information,

they’re not actually saying,

hey, there’s amino acids here,

or hey, there’s sugar here,

or hey, there’s essential fatty acids,

because the language of these cells is somewhat generic.

It’s just the firing of electrical potentials,

but that’s the key point.

It’s generic, and all three, or any of those three,

sugar, essential fatty acids, or amino acids

will trigger these neurons to signal to the brain

to increase dopamine.

And it is not coincidental

that omega-3 fatty acid supplementation

can help ameliorate some of the symptoms of ADHD

by way of presumably increasing dopamine

in this neuropod to dopamine pathway

that we talked about earlier.

The whole thing has a very nice logical structure to it

and points to, yet again,

the immense value of bringing the proper amounts,

maybe even supplementing the proper amounts

of omega-3 fatty acids

and the proper amounts of amino acids into the gut

as a way to supplant some of the stimulation

of these pathways that would otherwise be caused by sugar.

There’s actually a version of this where one could say,

if you want to reduce sugar cravings,

you might consider increasing

certain forms of amino acid intake

or certain forms of fatty acid intake.

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?

Well, these neuropod cells that respond to

and signal the brain when we ingest sugar,

as I mentioned, also respond to amino acids

and essential fatty acids.

We already talked about the essential fatty acids.

I make it a particular point to ingest

anywhere from one to three grams, that’s grams,

of EPA essential fatty acid per day.

I make it a point to do that

with the ingestive high quality omega-3s.

For me, the simplest way to do that,

and I think for most people,

the lowest cost way to do that

is to use some liquid form of fish oil

or some capsule form of fish oil.

You really do have to see how much essential fatty acid

in the form of EPA is in those.

If you try and do that only through capsules,

it can get kind of expensive

depending on which particular brands you use.

Some have more EPA, some less.

You can, of course, also do this through foods.

You can do this with non-fish sources

through things like algae, and there’s some other forms.

You can look it up online now,

plant-based sources of EPAs.

You can do this with high quality fish oil.

In any case, that does seem,

at least based on a modest amount,

but nonetheless solid literature,

to reduce sugar craving somewhat,

but that could easily be by mere replacement of calories.

So we don’t know yet based on human studies

whether or not the ingestion of those EPAs

is specifically activating the neuropod cells,

which specifically activates dopamine release

and bypasses the need for, or the craving for sugar.

We don’t know that yet,

but logically it holds up to assume that.

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 five grams distributed

through three or four different servings throughout the day

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

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.

And in fact, having talked about this previously,

a number of people that I know went out and tried this.

Now, this is, of course, is what I call anecdata, right?

This is not a quality peer-reviewed study.

This is anecdata.

Many of them have reported back

that they actually feel

as if their sugar cravings are reduced.

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 that 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.

Some of you with very hearty stomachs

can probably tolerate that.

You know, if you’re like my, you know, my bulldog,

which unfortunately passed away, but Costello,

I always imagine that if ever we did an autopsy on him,

he’d have like a license plate

and like a human being in his gut

because it seemed like he could ingest anything

with no issues.

But of course, many people have kind of sensitive guts.

So if you’re going to try taking glutamine

as a means to reduce sugar cravings,

just know that the studies are still ongoing.

Some people have achieved benefit.

Please also realize that there’s an entire literature

devoted to the potential hazards of increasing glutamine

if you have a preexisting cancer.

So if you have cancer, you’re cancer prone,

I would really discourage you from this approach.

And in any case, as always, talk to your doctor.

The logic nonetheless is there,

why increasing amino acid intake or fatty acid intake

might decrease sugar craving.

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 ones

that you might find in your cupboard or the grocery store,

and then get into some of the more extravagant,

or I should say, esoteric ones.

Many of which, however, can be quite potent.

The first of which is simple lemon juice, right?

Or lime juice.

There was an old lore and actually some papers

pointing to the idea that the ingestion of vinegar,

either white vinegar or wine vinegar,

could somehow blunt blood glucose

after the ingestion of sugary foods,

or the ingestion of a lot of carbohydrate foods,

or even just a big meal.

Actually, Tim Ferriss, I should say the great Tim Ferriss,

because I do have great respect for the fact

that he seems to be about 10 years ahead of everything,

both in terms of nutrition and skill learning

and things of that sort.

Many of the things that he predicted in his books,

the four-hour body and the four-hour chef,

actually turned out to be true based on scientific data,

some of which only exists in the animal models,

but now also some predictions that played out to be true

in both the animal models and the human model.

So I think that Tim certainly deserves a hat tip

for the fact that he experimented with these methods

and reported his experiences with those methods,

and that now some of them, many of them,

have been validated by what I perceive

to be quality science.

He talked about the fact that,

at least in his experiments on himself,

the ingestion of vinegar did not seem to blunt blood glucose

and he was using continuous glucose monitors.

These, incidentally, another example

of where Ferriss was early to the game

and the rest of us are kind of just in his wake.

He talked about the use of blood glucose monitors.

Those, I think at the time, were implanted below the skin.

Nowadays, there are less invasive blood glucose monitors,

things like levels and so forth,

and these are actually becoming pretty popular.

I’ve worn one of these before.

They’re actually pretty informative.

I learned, for instance, that when I go in the sauna,

that I experience a sharp rise in blood glucose,

and that makes sense because of the dehydration

associated with being in the sauna, a lot of sweating,

concentration of sugar in the bloodstream goes up.

So there’s some other things,

certain foods affect my blood glucose one way or another.

It’s kind of an interesting and fun experiment

that some of you might be interested in doing as well.

Regardless, there are now data pointing to the fact

that lemon juice and lime juice,

a couple of 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 experiments.

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 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 blood continuous,

hence continuous blood glucose monitoring.

So for those of you that are interested

in blunting your blood sugar response, certain foods,

that’s a simple low cost way to do that

if you want to explore it.

I will say, if you are fasting

and you already have low blood glucose

and you ingest lemon juice,

or I should say some lemon juice and water,

or lime juice and water,

be careful because you can actually become hypoglycemic,

right, for the very same reasons

that lemon juice and lime juice can blunt blood glucose

when your blood glucose levels are moderate to high.

You can also reduce blood glucose levels even further

when blood glucose levels are low.

Now that’s lemon juice and lime juice there,

but we can’t say that has to do

with acidic things generally.

And just as a side point,

many of you have probably seen in the store,

so-called adjusted pH waters,

or foods and drinks that are supposed to adjust your pH.

Hate to break it to you,

but your pH is very tightly regulated

throughout your brain and body.

You do not want this to change.

It is entirely impossible, at least in any safe way,

that you would become quote unquote more alkaline

by ingesting an alkaline water or something like that.

It is true that your pH, your alkalinity and acidity

varies in different compartments in your body,

that’s important.

Unless you are hemorrhaging or vomiting

or there’s something badly wrong with you health-wise

and you’re in a really dire circumstance,

you don’t want big shifts in your body pH

and your body has all sorts of ways

of buffering against changes in pH.

So I encourage you not to fall on the,

or hop on the bandwagon of adjusting pH

and becoming less acidic and that kind of thing.

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-ingestive 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 of course that means your tongue and palate.

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, where you have a situation

where you have two parallel pathways,

one that’s post-ingestive 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 taste,

excuse me, can adjust the neural response

to taste of sweet foods.

And in fact, we know based on the beautiful work

of Charles Zucker at Columbia Medical School,

that that’s exactly what happens.

They’ve measured the activity of neurons

at various locations in the so-called taste pathways

of the brain.

And they found that when particular tastes

like just sweet or just bitter or just sour

evoke certain ensembles of neurons

to fire in particular sequences,

when sweet and sour co-ingested,

when bitter and sour are co-ingested,

you get distinct ensembles,

meaning distinct patterns of activity of those neurons.

And of course, distinct patterns of downstream activity

within the brain and body.

So while it is still somewhat mysterious

as to how exactly things like lemon juice and lime juice

can reduce our blood glucose spikes

when we ingest those with sweet foods

or carbohydrate laden foods or with big meals,

you can use this as a tool with the understanding

that there’s a grounding in the biology

of the way these circuits work.

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 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.

In any event, there’s some debate out there.

If you look online as to whether or not Saigon cinnamon,

Kassia cinnamon, excuse me, or Ceylon cinnamon is best

for purposes of blunting blood glucose spikes.

But I think the, at least by my read of the data

and from what I found, it doesn’t really matter

provided it’s real cinnamon.

And you have to actually look and make sure

that it’s real cinnamon because a lot of cinnamon

that you buy is not real.

I do want to provide a cautionary note about cinnamon.

However, cinnamon contains something called coumadin,

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

because you’ll start to exceed the threshold

at which cinnamon could start to be problematic.

But certainly if you’re going to have a big meal

or a meal that has a lot of sugar in it

or a lot of carbohydrate laden foods

and you don’t want an increase in blood glucose,

you could put cinnamon in a beverage,

you could put cinnamon on food

in order to blunt that blood glucose increase,

reduce the glycemic index by way

of reducing gastric emptying time.

Again, just making sure that you don’t get out

past that one and a half teaspoons per day

because you really don’t want to start dealing

with any of the toxicity related to coumadin.

So we’ve talked about lemon juice and lime juice

and cinnamon, these are kind of commonplace

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.

And the one that comes to mind is of course berberine.

Berberine is a derivative of tree bark

and is a very, very potent substance

for reducing blood glucose.

So much so that it is on par with metformin

or glibenclamide, which are prescription drugs

specifically used to reduce blood glucose.

So using berberine is a serious step,

you should absolutely talk to your doctor about it.

I know of a number of people that use it

to lower blood glucose when they eat really large meals.

I know of a number of people that are using it

to get to some of the other effects of metformin

that people have discussed, things like activating

or tapping into the so-called AMPK pathway,

reducing mTOR.

These are people that are aiming their activities

at increasing longevity,

a somewhat controversial approach still,

but I know many people are doing it.

It is true that if you ingest berberine,

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 berberine

on an empty stomach.

I know some people can tolerate it.

I would say be very cautious about ingesting berberine

on an empty stomach,

or if you are in a low carbohydrate diet,

unless you really know what you’re doing

and you have a medical professional

to kind of guide you through that.

If I took berberine along with a very large meal

that include a lot of carbohydrates,

I can recall the days in which Costello and I

would eat a couple of pizzas

and then we might get ice cream, that kind of thing.

Then I felt perfectly fine on even up to 750 milligrams

or a gram of berberine.

It has the kind of unique property

of making you feel not overwhelmed

by the amount of blood glucose increase

that you’re experiencing from eating a big meal.

I don’t quite know how else to describe it.

It’s almost as if you can keep eating

and eating and eating.

And of course you have to protect your gastric volume,

you only have so much space in your stomach to ingest food.

I wasn’t using it to gorge on food.

I just heard about it.

I was interested in experimenting with it.

I don’t have any chronic blood sugar issues.

But again, when I took it on an empty stomach,

it made me hypoglycemic on a low carbohydrate intake,

hypoglycemic, not a good experience.

And again, an experience I think to avoid,

but provided there’s a lot of glucose in your bloodstream.

And certainly if you are of the experimental type

where you’re trying to regulate blood glucose,

berberine might be a good option.

But again, talk to your doctor.

It does have some other interesting effects

in terms of lowering total cholesterol

that are research supported

of reducing insulin a little bit.

Well, that’s not surprising.

If you reduce blood glucose,

you’re going to reduce insulin

because of course insulin manages blood glucose

in the bloodstream.

So I would place berberine,

and of course metformin and glibenclamide

in the kind of the heavy hitting potent tools

for regulating blood glucose.

Now this is an episode not about sugar per se,

but sugar viewed through the lens of the nervous system.

And what’s interesting about berberine, metformin,

glibenclamide and related substances

is that some of the effects are of course

on gastric emptying or buffering blood glucose

within the bloodstream, et cetera.

But there appear to also be some neural effects

of having chronically low glucose

or blunting blood glucose through things like berberine.

And some of those neural effects

include longstanding changes in the hormonal cascades

that are the consequence of having low blood sugar

and thereby changes in the neural circuits

that manage blood glucose overall.

The simple way of saying this

is that by maintaining low to moderate blood glucose,

either by not ingesting heavily carbohydrate laden foods,

so here I’m speaking to the low carb

and to the ketogenic types,

or by blunting blood glucose

through things like metformin or berberine,

even if ingesting carbohydrates, maybe even some sugars,

over time it seems that there’s a adjustment,

what we call a homeostatic regulation of the neural circuits

that control things like sugar craving.

And indeed some people report

feeling fewer sugar cravings over time.

Now I didn’t use berberine for a very long period of time.

I’ve never used metformin.

I have experienced a somewhat odd,

but welcome phenomenon of,

with each progressive year of my life,

I have fewer and fewer sugar cravings.

Why that is, I don’t know.

I suspect it might have something to do with my sleep,

and I’ll talk about that in a few minutes.

But if you’re going to explore berberine

or metformin or otherwise,

in addition to working with a doctor,

I think you should understand why you’re doing it, right?

I think that many of the effects can be quite potent.

They can happen in both the immediate term

in terms of regulating blood glucose,

they can send you hypoglycemic

if you aren’t careful.

They can also cause longstanding changes

to the neural circuitry

that regulates blood sugar over time.

Some of which might be welcome changes, right?

Reduce sugar cravings, for instance.

And if you’re really, really serious

about modulating blood glucose

through things like berberine,

the typical dose range again

is anywhere from half a gram to 1.5 grams daily.

That’s the typical dosages that have been explored.

And there are some other substances

like sodium cuprate,

which are known to augment the effects of berberine

via the AMPK pathways.

They basically can increase the ability for berberine

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.

So whether or not you’re low-carb, high-carb,

keto, vegan, carnivore,

these substances like berberine 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

and we actually have an episode called Master Your Sleep.

You can find that episode easily at hubermanlab.com.

It’s available in all the various formats,

YouTube, Apple, Spotify, et cetera,

and provides a lot of tools.

And on social media, I provide a lot of tools.

Often we have a newsletter that provides tools

on how to maximize sleep.

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,

Cell Press Journal, excellent journal.

And 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.

But 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.

And this is a really remarkable study.

They actually did this every 10 seconds

throughout the entire night.

So in little tiny 10 second bins,

meaning at very high resolution,

they could evaluate what is the metabolism

in the brain and body that people experience

as they go from REM sleep, rapid eye movement sleep,

to slow wave sleep and so on.

And I’ll go deeper into the study again in the future

because it’s so interesting and I think so important.

But 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 sleep deprived

or the quality of their sleep is disrupted,

that their appetite for sugary foods increases.

Now that was always assumed to be due to some

metabolic need that was triggered by the sleep deprivation

or by the poor sleep.

But in reading over this study,

some of the more important points made by the authors

relate to the fact that, well,

sleep is known to have incredibly important effects

on brain and body for a variety of systems,

immune system, neural functioning, et cetera.

This very organized sequence

of particular forms of metabolism

being active during particular phases of sleep,

which are very, very well orchestrated as we know,

slow wave sleep and REM sleep being orchestrated

in 90 minutes, so-called ultradian cycles

and so on and so forth.

Is thought to perhaps set up the brain and body

to be able to regulate itself in the waking hours.

And therefore, when people are sleep deprived

or deprived of certain forms or states within sleep,

such as rapid eye movement sleep,

that it creates a disruption

in a particular set of metabolic pathways.

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,

if you look at the sum total of the data on obesity

or on type two diabetes or on metabolic syndromes

of any kind, you almost always see disruptions in sleep.

Now, some of those could be due to sleep apnea

caused by even just the size of somebody’s neck

or the weight of their body.

In other words, we don’t know the direction of the effect.

Metabolic syndromes could disrupt sleep,

which disrupt metabolic syndromes.

And indeed the authors point out quite appropriately

that they don’t understand the direction

of the effects that they observe either.

But 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 the takeaway is,

while there are extravagant and potent

and interesting ways to regulate glucose,

everything from cinnamon to lemon juice,

to berberine, to sodium caprate, to behavioral tools,

to the mere understanding of how the direct

and indirect pathways go from the gut to dopamine, et cetera.

If you’re not establishing the firm foundation

of proper metabolism,

all of those things are going to be

sort of rearranging deck chairs on the Titanic

as sometimes described.

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, et cetera,

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.

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