Hello everybody and welcome to the VP Life podcast brought to you by Vitality Pro.

My name's Rob and I'll be your host on today's episode.

Today we're joined by Dr.

Greg Potter.

Greg has a PhD in metabolic health from the University of Leeds and works

with athletes and other high achievers to help them dial in their health so

that they can operate at their best.

While this may seem somewhat the norm in the online coaching

space, Greg is different.

See, as part of my job I get to speak to a lot of intellectuals and as you'll

hear shortly, Greg has an incredible ability, way outside the norm in fact,

to dissect scientific literature and provide his clients with information

that actually moves the needle.

Today I had the opportunity to discuss Greg's passion topic with him.

Sleep.

So expect to learn exactly what sleep is, how your nutrition can affect

your sleep, whether sleep chronos helps are real, and so much more.

And with that, on with the show.

Good morning, Greg.

Thank you very much for joining us on our podcast today.

I know we're going to be delving into a lot, especially around sleep, but first

and foremost, would you just like to introduce yourself, who you are, what it

is you do, and all of that good stuff.

Sure.

Yeah, relevant to this conversation, I studied sleep, nutrition,

and metabolism for my PhD.

And throughout my studies, both my undergrad, masters, and PhD, I've

coached people in various capacities.

Initially, a lot of that work was with athletes, but more recently,

I've done a lot more work in health coaching in general.

And some of that is specifically with people who have ongoing sleep

issues, which are often comorbid with mental health problems.

But I've been involved in various other businesses along the line too,

including everything from trying to scale health coaching through

things like apps to working with a business that runs retreats.

And I've been involved in several different nutrition businesses.

And one of the projects I'm working on at the moment is formulating nutrition

products for a startup, which is bringing to market a product next

year intended to help increase health span and potentially lifespan too.

So that's a little bit about me, but the way that I try and help people

is through lifestyle in a way that's sustainable and a way that accounts

for all the different moving parts and meet people where they're at.

So I'll pause there.

Fair enough.

Yeah.

A very sort of functional approach to it.

You were or are involved in the Human os, is that correct?

I was, yeah.

I worked there 2016 to 2019, and I helped Dan with a lot of content creation.

So while there I made a couple of courses, wrote some blogs, hosted the

podcast a few times, created some guides.

And just generally gave lots of feedback on the platform and whatnot.

And to this day, he's a very good friend of mine, so no longer working

with him, but on very good terms.

Uh, it's awesome.

I, I played around with it a little bit in the past and, uh, I just, I have no

clue how I know that you were involved.

Uh, I'm sure I heard it somewhere, but yeah, no, it, it just, uh, Sort of

jogged my memory as you were saying that.

Okay, so um, I suppose let's get into the nuts and the bolts of it.

Bit of a dumb question maybe, but what is sleep?

Because I actually don't know what sleep is apart from not being awake.

People have tried to define it.

And the most commonly cited definition in textbooks and academic papers is a

definition that's put forward by, I think it was Bill Dement and Mary Karskadan.

And it's, it's a very descriptive definition.

And I don't recall it word for word, but it's something along the lines of

a state of relative inactivity often accompanied by postural recumbence

in humans, and it's a state in which you are relatively detached from the

environment, but it's rapidly reversible.

So that obviously is what sleep is, but I think the thing that

most people are interested in.

is what functions does it serve?

Because superficially sleep is a very strange behavior and you might

have thought that there'd be strong evolutionary pressure against the

selection of something like sleep because during sleep you're vulnerable.

You aren't keeping an eye out for predators.

You're not eating and therefore supporting your energetic needs

and Most of the time there are incredibly rare exceptions to this.

You're not trying to procreate either and so Given all of that the odds would

surely be stacked against the evolution of sleep, but I think Fundamentally,

the reason that we do sleep is To pay the price for wakefulness Because

while we're awake, we're interacting with the environment that exposes

us to lots of different pathogens.

We accumulate damage while we're moving around and interacting with

different organisms and the environment.

And we also need to integrate the experiences that we've

had so that we can learn.

And so sleep is a bit like that.

the pit stop in a Formula One race and that you need to occasionally change the

tires and put some fuel in the tank and puts the body in a state that is conducive

to that type of restoration and learning.

Fair enough.

I suppose a good place to go with this is what actually happens

during sleep, just at a high level.

I think people often hear about terms such as REM sleep and deep sleep.

But what actually are they and if we sort of go through the stages of sleep

and physiologically again, just at a high level, how does sleep play out?

Yeah, it plays out at a specific time within the biological day.

So we have the system of clocks throughout our bodies, which

optimize our bodies for different functions at different times of day.

And during the biological nighttime, we are disposed to sleeping.

And during sleep itself, as you alluded to, we cycle through

different stages of sleep.

And these cycles are often described as lasting 90 minutes.

They're actually called sleep cycles.

Nothing like as orderly as that.

They change in duration over the course of the night, but they also vary quite

a lot from one person to the next, and they can be anywhere from about 70

minutes long to about 120 minutes long.

And if you look at the stages of sleep, we can broadly classify these into rapid eye

movement or REM sleep and non REM sleep.

And if you look at a night of sleep, then you have most of your non REM sleep

in the first part of the sleep period, and you have most of your REM sleep in

the second part of the sleep period.

That's to do with how sleep is regulated, but Looking more closely

at non REM sleep, when you first fall asleep during the night, you're, you're

likely to enter what's called stage one non REM sleep, which is like a

bridge between wakefulness and sleep.

It's the lighter stage of sleep.

It occupies a small proportion of total sleep.

From there, you drop down into a slightly deeper stage of sleep.

And by deeper, I mean that it's hard to wake someone.

And this is called stage two REM sleep.

Non REM sleep, which makes up the majority of sleep.

It comprises roughly 50 percent of most people's sleep, and

it has certain features that make it particularly helpful.

So during this stage of sleep, for example, you have what are called sleep

spindles, which are these bursts of electrical activity of a certain frequency

that are important to maintaining sleep during periods of instability in sleep,

so periods when you could wake up.

But they're also important to basically transferring information from a short

term limited capacity storage depot in a structure in the brain called the

hippocampus to a much larger capacity storage depot elsewhere in the cortex.

And in doing so, it frees space in the brain.

to learn new things the next day.

Is that the consolidation of memory then?

Yes, and the reality is it's likely that all stages of sleep are involved in memory

formation, but that is consolidation.

And we then go from there into the deeper stage of sleep.

Which is stage three sleep, sometimes called slow wave sleep because of its

characteristic high amplitude, slow waves, which basically start around the bridge

of the nose and then sweep backwards.

through the brain.

And these are also important to the formation of memories, but slow wave

sleep is particularly key for various different housekeeping functions, both in

the brain and in the rest of the body too.

So in the brain specifically, your brain has its own waste disposal

system called the glymphatic system.

You've probably heard of the lymphatic system, which is your

immune system in basic terms.

And your brain has its own immune system and there's a particular

type of cell that's important to this called glial cells.

So it's the glial lymphatic or glymphatic system.

And during the deeper stage of sleep, it's a bit like the

plumbing in your brain opens up.

And because of that, various different byproducts of metabolism that have

accumulated during prior wakefulness can be cleansed from the brain by

pushing around a certain type of fluid.

through the brain.

So in that way, it's important to brain health, but it also has

similar restorative functions in the rest of the body too.

So during slow wave sleep.

You produce much of your growth hormone and this type of pulsatile

growth hormone production seems to be important to remodeling certain

tissues like connective tissues.

It's also relevant to metabolism.

So during these different stages of sleep, we actually change the

way that we burn certain fuels.

And during these deeper stages of sleep, we tend to rely more

on fat oxidation and carbohydrate metabolism relative to REM sleep.

And then The deeper stage of sleep is also important to your immune function

outside of the brain, and actually to the formation of memory in the immune system.

So you can broadly split your immune system into an innate

system, which is what you're born with, but also an adaptive system.

Your immune system has a memory of things that you've been exposed

to, that you want to rapidly mount immune response to in the future.

This is obviously the basis of things like vaccinations and slow waves lead

to, slow wave sleep is very important to some of that memory formation.

And then typically you'll go from that deeper stage of sleep into rapid eye

movement sleep, which makes up maybe 20 percent of sleep or so in lots of adults.

And it's an unusual state.

It's sometimes called paradoxical sleep, because while if you look at activity in

the brain going by blood flow, parts of the brain are as much as 20 percent more

active than they are during wakefulness.

Most of your muscles, your non essential muscles, so I'm not talking about muscles

that are involved in breathing, I'm not talking about your myocardium, your

heart muscle, but many of your other muscles, your biceps, your quadriceps,

your lumbar, spinae, whatever you want to pick, more or less paralyzed.

It's not true of everyone.

There are rare instances where that's not the case.

But in that way, you're in this strange state where you've got this

very active brain, and your muscles are paralyzed, which presumably is so

that you don't act out your dreams.

And there's a particular sleep disorder where that regulation of

your skeletal muscles breaks down and people start acting out their dreams

called REM sleep behavior disorder.

And during REM sleep, there are also various other changes.

that make it distinct from other stages.

So whereas in non REM sleep, if you look at stage one to two to three,

the deeper in the, it becomes harder to wake someone, but also things like

the rate at which you're breathing, your respiratory rate slow down.

In REM sleep, if you look at things like your heart rate, then your

heart rate can actually fluctuate quite a lot during this time.

And basically the main functions of REM sleep.

While disputed, seem to relate to a few things.

So one of them is that it's very important to emotion regulation.

It's a kind of emotional first aid that's often described that way.

Another is that it seems to be very important to creativity.

So the way that this has sometimes been described by people like Robert Stickgold

is that REM sleep is helpful to giving you a sense of the gist of things.

It's the kind of sleep that you'd want before a multiple choice

questionnaire test where you're not sure what the right answer is.

But you've got an inclination that it might be this.

And what seems to be happening during this stage of sleep is that you are

going back through many different autobiographical memories that have

taken place, sometimes many years ago.

And then you're integrating them with recent information and your

day to day experiences and you're looking for patterns between things.

And in this way, it seems to be very helpful.

for creativity and come out with novel solutions to problems that

previously seemed intractable.

So that's something about the different stages of sleep.

But I think it's important to note that it's not entirely clear

that all of the brain is in a sleep stage at the same time.

Sleep doesn't seem to be as unitary as that.

And while this hasn't been well demonstrated yet, there's some

evidence showing that different parts of the brain can be in different

sleep states at the same time.

Which throws a spanner in the works when it comes to making sense of a

lot of historic sleep literature.

But this might explain various different unusual phenomena

that take place during sleep.

For example, if you think of sleepwalking, it could be that parts of the brain

that are involved in consciousness and awareness are fast asleep.

Because sleepwalking is often during quite a deep stage of sleep.

Whereas the motor cortex, which gives rise to Sleepwalking.

voluntary movements, is showing wake like behavior.

Or if you think about lucid dreaming, it could be that part of the brain

that's involved in consciousness is in a wake like state, whereas many other

parts of the brain, like the motor cortex, are in a sleep like state.

So, sleep isn't a monolithic phenomenon, and I think part of the appeal of it

is that it is so interesting, we learn so much more about it, each year.

I'll pause there because I realize that was already quite a long

answer, but hopefully that gives you some background to the different

sleep stages and, and some of the things that they're important for.

No, that's perfect.

And that sort of really underlines, I suppose, why it's sort of

almost the foundation of health.

I want to sort of in a minute go into sort of your thoughts on some

of these sleep trackers, specifically your auras, your whoops, and what

you think of their deep sleep scores.

But um, first I, what I'd like to sort of quickly touch on are your

thoughts on when we go to sleep.

There's often a lot being said about needing eight hours of

sleep almost indefinitely.

I mean, obviously depending on genetics, some people can get

away with less, some people more.

But when you get those, just broadly speaking, eight hours

in, is that important or does it for the most part not matter?

So if you were to go to bed at 12 a.

m., what's that p.

m.?

I never get that one right, and then wake up at 8 a.

m., 8 hours later in the morning, 8 a.

m.

Is that, is that important?

Restorative and as physically rewarding as, say, going to bed at eight or nine

and then getting up at five or six.

Does that, yeah, does that play a significant role in the quality

of sleep when you go to sleep?

Taking a step back, the way that I think that we should think about sleep

health has been heavily informed by a psychiatrist named Daniel Bicey.

And a few years ago, a decade ago now, he wrote what has become a

highly cited paper And it was about how to define what healthy sleep is.

And in it, he discussed different dimensions of sleep health.

A lot of people are focused on sleep duration.

The sleep duration is important, but sleep timing is important too, as is the

quality, as is the regularity of sleep.

And really you could apply regularity to any of those other dimensions.

So, yes, timing is important, and it's most important within the individual,

and what I mean by that is that, as I mentioned at the very start, we have

this network of different clocks in our bodies that prime us for sleep at

certain times during the 24 hour day.

And If we try and sleep during the biological nighttime, when our bodies

are primed for sleep, we're likely to have higher quality sleep than if we try

to sleep during the biological daytime.

And this is the perennial problem that shift workers experience.

On average, they get a bit less sleep than the rest of us, but not

necessarily that much less sleep.

And some of them probably don't get much less sleep at all, and one of their issues

is just that because they're trying to

sleep during the biological daytime, they really struggle with their sleep quality.

And there's a sleep disorder named shiftwork disorder that affects

about a quarter of shift workers, which sure enough is characterized by

lots of fatigue and sleepiness when awake, because they're often awake

during the biological nighttime.

And then exhaustingly, when they try and sleep, They have insomnia symptoms

and they really struggle to stay asleep.

So when you sleep absolutely does matter.

But I think the important thing is when you as an individual are trying to sleep

relative to your biological nighttime.

But obviously this interacts with different societal pressures

that are imposed on you.

For example, if you are a night owl, then you might have to

wake up to an alarm clock each morning and left your own devices.

You might choose to go to bed at 2am, but you have to be up at 7am to get the train

into the city to be on time for work at 8.

30.

And so you have a restricted sleep opportunity because of that.

And ideally, you would work quite different working hours.

But the way that your sleep is constrained by those pressures means

that the onus is on you to try and shift your sleep earlier to give

yourself a larger sleep opportunity.

But that might be running counter to your natural disposition because I

know there's some contention about the veracity of what are called chronotypes.

So whether you're more of a Yeah, whether you're more of an early

bird or a night owl, some people will say, Oh, they don't exist.

They absolutely do exist.

And the reality is that if you look within a population, they're probably

distributed relatively evenly.

There's probably a bell shaped curve.

If you put people under a standardized light dark cycle and you compared

people of the same age and biological sex, you would find that naturally

some people are earlier birds and they would have faster clocks.

If you left the clocks ticking without any time queues, like light exposure,

food timing, physical activity, and so on, then some people would be much more hour

ish and they would have slower clocks.

Their clocks would tick at a pace substantially longer than 24 hours.

Yeah.

Now I was just gonna play Devil's Advocate and just sort of, because I'm

definitely fallen to the camp of being maybe, yeah, a little on the edge about

the sort of chronotypes and sort of looking at it more from an ancestral lens.

Do you not think that when I sort of accounting for a normal wake

dog cycle, that those individuals who are quote unquote night birds

or night owls would maybe not sort of shift their circadian rhythm?

to a more traditional sleeping pattern if they weren't exposed to so many of

these sort of zygabas as I think they're called that sort of, yeah, interfere with,

I suppose again, what is traditionally thought to be a normal circadian rhythm.

Yeah, they, they absolutely would shift.

And, and the best example that we have of this in my opinion is a couple of studies

that were done on people going camping for a few days in the rocky mountains and they

did one experiment during the winter when the nights are long and one experiment

during the summer when the nights are shorter and they found that before the

camping there was large dispersion between the earliest birds and the latest owls.

And after just a few days of camping, the range of sleep timing narrowed

dramatically, and they were, in general, sleeping in closer synchrony with the

natural light dark cycle, such that the early birds didn't really shift, but the

night owls became substantially earlier.

So, yes, if you gave people strong time cues where they were exposed to

lots of daylight during the day and minimal light at night, then there

would be a much smaller gap between the earliest and the latest people.

That's absolutely the case.

And the reality is that in our modern context where you've got lots of

artificial light at night, and many of us spend 90 percent plus of our

time indoors, We have these weak time cues and that increases the range of

chronotypes or increases the range of sleep timing being more correct that we

see in the general population, but to me, chronotype is a biological construct.

And it's, it's driven by genetics.

We know something about the genetics that makes some people be much later types than

others or much earlier types than others.

And that there are a few mutations in certain clock genes that have

been identified that make entirely entire families of people much

earlier than the rest of us.

And we know less about the genetics.

that makes some people very owlish, but we know something about those genes.

So, it's a long way of saying that, yes, if we all lived more ancestral lifestyles,

the disparity between the earliest and the latest people would be a lot smaller.

However, it would still be there because of these genetic differences.

There outliers, it's just that most people would cluster Around the average.

I just want to take a quick step back towards what you, a quick step

back towards, a quick step back and talk about shift work again.

Again, physiologically, do you think that the reason most people who do

sort of partake in shift work struggle is, is because they aren't producing

as much melatonin when they should be?

And is that then sort of resulting in them not being able to sleep

during the waking part of the day?

I wouldn't, yes it does.

I wouldn't focus specifically on melatonin.

Melatonin is used a lot in biological rhythms research because

in the right conditions it gives you a very clean readout of when

it's the biological night time.

And for that reason it's widely used to assess the timing of the master

clock in the circadian system, the suprachiasmatic nucleus, because it's

got relatively direct connection to the pineal gland, which synthesizes

melatonin during the biological nighttime.

And so it's used to try to identify where someone is within the course of

their biological day, biological night.

So it's helpful.

However, obviously it can be readily masked by light exposure because you

can take someone during their biological night time, expose them to a brief bright

light pulse and their melatonin synthesis would be turned off pretty much entirely.

And actually a lot of us probably experience that every night because

we're not particularly particular about our light dark cycles.

And so we expose ourselves to lots of electric lighting before we go to bed.

And then we flip the lights off.

And actually our biological nighttime did start a couple of hours ago, but all

that light exposure has just squashed any melatonin that would otherwise

have been synthesized during that time.

So returning to question, I think.

Part of the reason why they're struggling so much with their sleep and their

health is because they are trying to sleep during the biological daytime.

And obviously melatonin synthesis is relevant to that.

And it could be that if you looked at the area under the melatonin curve each

day, so the total amount of melatonin that's circulating in the blood or saliva

or six alpha toxin melatonins in the urine, then the total amount is lower

than somebody who is working during the daytime and sleeps in alignment with that.

with their biological rhythms, and could that contribute to some health issues?

Yes, potentially.

But I think in the case of shift work, we can broadly distinguish between

circadian and sleep disruption that comes with the shift work, and then other

stresses that they might face that might distinguish them from the rest of us.

Because if you think about shift workers, then they're trying to maintain

relationships with non shift workers.

That's tricky.

and their lives are out of sync with the rest of environment.

And so that plus the fact that there are probably differences between

things like the amount of money that they earn and so on and therefore

access to healthy foods and healthcare between them and non shift workers.

Those factors do contribute to some of the health disparities that we see.

But then certainly, the disruption to sleep, trying to sleep during

the biological daytime, and also things like mistimed eating, and

mistimed light exposure, and mistimed physical activity, all of those

things probably do contribute.

And they also make it harder to make healthy lifestyle decisions, because

if you're forever short on sleep, then if you look at the research on how that

influences things like decision making, you're going to find it harder to make

good health choices because you're probably going to be a bit more impulsive.

You're likely going to be slightly more disposed to engaging in risky

behaviors than the rest of us.

And so you might find it harder to say no to the donuts that

someone brings into work.

And because of that, it has knock on effects.

And those are then amplified by the fact that now, in this instance, your

digestion and your metabolism have been scuppered by your recent sleep

loss and circadian misalignment.

That's a brilliant sort of point, actually.

And I'd like to discuss it in a bit more detail, but sort of sleep

and metabolism, sleep and appetite.

What exactly are the mechanisms there that are driving dysregulated appetite

when somebody is not getting enough sleep?

Because, yeah, it's often said that, uh, a poor night's sleep will result

in you making poorer food choices.

But what, what's going on there specifically?

I think there are a few things going on.

One of them is very obvious and it's simply that the less sleep you get and

the shorter your sleep opportunity, the more hours you are awake and therefore

the more hours you have access to food.

And so you might distribute your food intake over more hours each

day, and that in turn increases your total energy intake.

Even controlling for that though, people probably do tend to eat slightly more.

If you look across studies of either sleep deprivation, where they're not

allowed any sleep whatsoever, or sleep restriction, where they might have

several nights of insufficient sleep, so perhaps they only have a five

hour sleep opportunity for instance.

than on average people.

consume roughly 250 more calories each day when they're short on sleep.

Some people actually consume less calories, but on average,

most people do consume more.

And beside the fact that they're spreading their food intake over a longer period,

there are probably a few things at play.

So naturally a lot of people have looked at the endocrinology of this.

So is this driven by changes in hormones that are involved in

appetite regulation and satiety?

And frankly, the research on that is a little bit all over the place.

If you look at meta analyses, then looking at ghrelin, for example,

doesn't seem to be a clear effect on ghrelin when you might've expected

there to be an increase in ghrelin because it tends to promote food intake.

And likewise, the data on leptin, which is this hormone that's largely produced

by fat tissue, which is representative of your long term energy status,

although it does respond somewhat to short term fluctuations in energy

intake and energy availability, and it in turn tends to reduce food intake.

The data on leptin again aren't that consistent.

It could be that the ratio between the matters, it could be that there

are some other hormones that are affected by insufficient sleep.

So people have looked at things like certain endocannabinoids,

so these endogenous cannabinoids that tend to promote food intake.

This is why you get the munchies after you smoke cannabis.

Some of the cannabinoids tend to promote food intake.

But overall, it's quite hard to parse the literature.

There might also be some small differences between the biological sexes.

And I won't, I won't go into the details of that, because I think it's probably a

level of detail that's not necessary here.

But putting aside changes in, in hormones, if there are any, and I think

there probably are some, but I don't think they're a massive contributor.

then there probably are differences in what's called

hedonic or non homeostatic eating.

where you're not eating because you're really hungry, you're eating because foods

are harder to say no to at that time.

And there have been lots of imaging studies where people have looked

at patterns of electrical activity in the brain, patterns of blood

flow in the brain, in response to things like food images.

And in general, the brain that has been sleep deprived seems to respond

differently to food related cues in ways that make it a bit more impulsive around

food and therefore more likely to go for a short term reward like delicious food.

than a longer term reward like saying no to the food for now because

your health is important to you and you're trying to lose some body fat.

So is it not just a dopamine issue do you think?

Is it not maybe a result of less sleep resulting potentially and I'm

just stringing mechanisms together here, but more oxidative stress, more

inflammation and potentially less dopamine that is then driving that um,

desire to find a, find a dopamine hit.

Yeah, I wouldn't focus on, on dopamine because obviously the, the

neurochemistry of it is very complicated and that's also just one piece of

the puzzle, but, but certainly.

The brain seems to be very motivated by food when it is short on sleep.

And that's no surprise because extended wakefulness continues

to tax the brain's energy stores.

And so your brain wants energy to refuel itself.

It's just that it tends to try to gain more energy than is needed

to actually replace any additional losses that have taken place as a

result of the insufficient sleep.

And if you look at some of the literature on how the brain responds

to insufficient sleep, then there are changes in things like the limbic system.

There are changes in some of those reward pathways too.

There are lots of different changes that take place, but one of the commonalities

seems to be that the frontal cortex, which is the most evolutionarily

recent part of the brain, which is very important to things like reasoning,

long term planning, self control seems to communicate less effectively than

some of the more primitive deeper parts of the brain that are more

responsive to things like different types of stresses that make the brain

fearful or worried or hungry or horny.

And so it seems that The ability of the frontal cortex to exert control over the

limbic system and some of these other parts of the brain that are involved

in, in things like responding to food is compromised by the insufficient sleep.

And I think that might turn out to be more important than any hormonal

changes that are taking place.

What are your thoughts, I suppose, sort of tacking on from that on food timing

with regards to sleep, especially sort of, Yeah, again, healthy levels of sleep.

Um, there's a lot being said about sort of restricting your calories.

Uh, or your consumption of food too early in the day and then

providing a buffer between your last meal and when you go to sleep.

Personally, I find that if I go to bed hungry, I just, um,

there's just an increase in catecholamines and I cannot sleep.

Whereas other people, the opposite seems to be true.

There's an increase in metabolism and then they, yeah, can't sleep

for almost the opposite reason.

Do you think that food timing, to repeat what I've just said, relative to when

you go to sleep is important or is it sort of somewhat blown up in proportion?

I think, I think it is important.

I think how important it is depends on the person.

And I also think that when people should stop consuming anything

that contains calories varies a lot between different people.

And to give you a few examples of this, if you take somebody who's got lots of

energy stored on their body, they could probably go days without eating, without

the recent low energy availability.

dramatically, negatively affecting their sleep.

However, if you are already lean and you go to bed hungry, then it makes sense

that that would impair your sleep more.

So I think some of this depends on things like baseline levels of body

fat and physical activity in your recent physical activity history.

So taking another instance, think of an athlete who's training twice a day

in an energetically demanding sport.

with good body composition.

For them, if they try and use early time restricted eating and they finish

their food intake at 3pm, that might not be a good thing for their sleep.

Similarly, if you think about a child that's growing that needs lots of

energy to invest in building new bones and muscle tissue and the nervous

system and so on, then early time restricted eating is not the way to go.

So I think the eating window depends on a variety of factors, but there are

probably a few simple heuristics that apply to most people, and probably

to everyone listening to this.

So, first, you don't want to go to bed either feeling

stuffed or feeling famished.

There might be instances when you're on a fat loss diet, and you have been

on that diet for weeks or months, and you're generally hungry where

occasionally you do go to bed feeling hungry but it might be worth that for you.

And also it's important to note that your hunger patterns are

entrained by your food intake.

So one of the interesting things that we see in the research on early

time restricted eating, which often involves having people restrict their

food intake between 8am and 3pm, is that They don't actually have

a massive surge in hunger in the evening, which you might have expected.

Because if you look at circadian rhythms and appetite, circadian rhythms

and appetite tend to promote food intake most relatively late in the

evening, at about 8pm for a lot of us.

But with early time restricted eating, Initially, you might find the evening

really hard because you're used to eating at that time, and therefore

you have lots of hunger at that time.

But after a few days, you might find that your body is no longer

expecting food at that time, and therefore your hunger levels over

the course of a 24 hour day increase.

So just know that when you eat does influence your patterns of hunger,

and in some instances it's worth going through a few difficult days because

things will actually get easier.

But going back to what I was saying, going to bed, neither stuffed nor

hungry, and I think for most people not consuming any calories in two hours

before lights off is a good rule of thumb.

I don't think that's overly restrictive.

There might be rare exceptions, like athletes with late training sessions, for

instance, who need to, say, top up their muscle glycogen stores and support protein

synthesis after the training session, which would mean that that particular

recommendation is out the window.

And the same could go for, for children and adolescents during

certain stages of their development.

But I think for most adults, that's reasonable.

And part of the reason for this is just that if you look at circadian

regulation and metabolic control.

It's such that in general, the body does tend to respond worse to food

intake late in the biological date.

So looking at glucose tolerance, for instance, so how much your blood sugar

swings in response to a standardized bolus of glucose, it's substantially worse at

8pm than at 8am on average across people.

And there are various factors that we go into as to why that's the case.

But that's why, especially for people who are relatively sedentary, I

think front loading a lot of their carbohydrate and fat intake within

the waking day is a good way to go.

If, however, you've got very good metabolic health, or if you do very

strenuous exercise late in the day, so let's say that you finish work at 5.

30pm and you go straight to the gym, and in the gym you do a full body resistance

training workout for 45 minutes, and then you do 15 minutes of installs.

You've just depleted lots of muscle glycogen and you might want to replenish

those stores after your workout.

If you've got good metabolic health, then that's a, that's a great

time to have lots of carbohydrate.

So there are exceptions, but I think those general recommendations

work well for a lot of people.

And then, of course, based on what I just said, you can start to think

about this in terms of different days.

So in the sports nutrition world, In the last decade or so, there's been

quite a lot of talk of periodized nutrition, not just periodized training.

And so there might be days within a micro cycle, which lasts a week, where

you eat very differently to other days.

So you have those strenuous workouts where performance is a priority and recovery

from those workouts is a priority.

You might consume a lot more food in total on those days.

And a lot of that might be.

a bit later in the day too.

Whereas other days that are rest days or active recovery days, you might

be consuming much less late in the day and a little bit less in total.

So another long winded answer, but as usual, it depends, but neither

hungry nor full and two hour cutoff, I think is reasonable for most people.

Fair enough.

Yeah, that was an amazing answer.

Thank you.

I'm going to listen to that again.

Moving forwards, um, looking at sleep and specifically jet lag, it's sort of

something that's been of interest to me of late, and then utilizing, and utilizing

food potentially as a zeitgeist, but something to reset the circadian rhythm.

Um, when you sort of moved into a new time zone, do you think

it's an effective tool to sort of help reset this circadian rhythm?

Or is this where compounds such as melatonin are, are generally

sort of utilized more effectively?

So just to step back, a Zeitgeber, that's from a German word that means time giver.

These are different stimuli.

that can change the timing of circadian rhythms because you need to reset

your circadian clocks each day because they don't tick at precisely 24 hours.

And the most important of these for humans is the light dark cycle,

and that's particularly important to the timing of the master clock

and in turn your sleep timing.

But there are other zeitgebers too.

So I mentioned physical activity and that seems to be one.

Probably mostly for skeletal muscle clocks, maybe for bone clocks,

possibly for cardiovascular system.

A little bit for the central clock too.

But it seems likely that nutrition is a time cue as well.

In particular for organs that are involved in digesting, and metabolizing food.

The little research that's been done so far shows, for instance,

that if you take two groups of mice and you feed one of them from 6 a.

m.

to 6 p.

m.

and another from 6 p.

m.

to 6 a.

m.

I hope I said that correctly, then within days if you, if you take samples of a

tissue like the liver, the timing of gene expression is 12 hours out of phase.

between the two groups.

It's completely inverted and there's preliminary evidence showing that some

of these peripheral clocks in humans, so all the clocks that exist outside the

master clock in the brain, and here I'm talking about fat cells specifically,

but maybe it's true of the pancreas and the liver and the gut tissue and so on as

well, do respond to food intake as well.

And so really what we're looking for to organize our circadian clocks

appropriately is high amplitude cycles that are characterized by lots of

daylight during the day, physical activity during the day, food intake

during the day, and then resting and fasting in darkness at night.

And of course, in the case of jet lag, You travel across many time zones and

initially your body's clock is stuck back at home and all these different clocks

are trying to catch up to the new time zone and they do so at different rates

and this is why for instance you might find that your digestive issues that

you experience in the new time zone, maybe you get a bit constipated for

instance, they resolve quite quickly.

but your sleep takes longer to catch up with the new time zone.

And so what we're trying to do is give ourselves appropriate Zeitgeber

schedules to entrain our clocks to the new time zone as quickly as possible.

And for the master clock in the brain, the way that we do that

is appropriate exposure to light.

And you can use melatonin as well to speed the rate at which the master

clock adjusts the new time zone.

But in the case of peripheral clocks, we're trying to shift the timing of

our nutrition such that we can get those clocks on time with the new time

zone as quickly as possible as well.

So in terms of where the rubber meets the road, what I would say

is that being pragmatic, there's an excellent app called Time Shifter.

I have no affiliation with it whatsoever, but you can try.

I think they give one free trip, and you just enter your flight details,

and it gives you a personalized schedule of when to experience bright

light, when to avoid light, when to take naps, when to use caffeine.

The caffeine is less about the circadian system, but it probably does affect

the circadian system a little bit.

It's more about homeostatic sleep drive, which is like the hunger

for sleep that grows in your body the longer that you've been awake.

So you can use that to address light schedules, naps, and you can also use that

to give recommendations about when to use melatonin if you want to use melatonin.

In general, melatonin is more helpful if you're traveling east than if

you're traveling west, although there are rare exceptions to that.

In terms of food intake, it's really tricky to be prescriptive

at the moment because we don't have what are called phase response

curves established for food intake.

And a phase response curve is basically a diagrammatic representation of, of how a

particular clock responds to a Zeitgeber at different times during its cycle.

So if you're listening to this, you could, you could look up the phase response

curve for bright light, for example.

Or the phase response curve for melatonin.

In the case of the phase response curve for melatonin, you'll see that if you

take someone who's got a 10:00 PM sleep onset and a 6:00 AM sleep offset, if they

take melatonin in the few hours before sleep, they'll tend to accelerate their

clock and pull their sleep earlier.

Whereas if they take it in the few hours after they wake up in the morning, that

will tend to to push their clock later.

We don't have that plotted for food intake because the necessary

experiments haven't been done.

So what do we do for the time being?

What I would say is, while you're in transit, moving between the

different time zones, frankly, your digestion and metabolism is

likely to be a little bit of a mess.

And in part because of that, if you want to be particular about

this stuff, you don't have to, you can just enjoy plain food.

If it doesn't bother you that you're going to have a couple of days where things

go a bit haywire, but If you are really prioritizing your health during this

transitional stage, you could actively look for high protein items that are

lower in carbohydrate, probably a little bit lower in fat too, and you consume

slightly less energy in total because your blood sugar and your blood lipids

probably as well are going to swing more in response to food intake during

the state of metabolic dysregulation.

So during that time, you're trying to hold onto your fat free mass using the

protein, have things which are relatively easy to digest to avert any gut issues,

and keep carbohydrates and fats a little bit lower because of that dysregulation.

And so this could include things like certain high protein snacks.

It could be protein bars.

There are a few good ones nowadays.

It could be things like jerky, cheese.

For fat and fiber rich sources, you could have things like

mixed nuts and low sugar fruits.

And you can pack those items with you and take them with you.

to skip plane food.

In terms of timing while you're in that transitional stage, one of the things

that I've played with, in my mind at least, is the idea that there's, there

are certain times during which it's when you would be eating both at your

origin and at your destination too.

So if I take the example of flying from the UK to the West coast of America,

it's an eight hour time zone difference.

And so if you normally spread out your food and take over 10 hours each day, your

final meal of the day in the UK coincides with your breakfast in the new time zone.

So I think it makes a little bit of sense to concentrate a lot of your

food and take around that time, because I think you're less likely

to experience digestive issues.

And then when you get to new time zone, wherever you are, whichever direction

you're going, after your first full day, full night of sleep, so complete

sleep opportunity, I would fully switch your meals to the new time zone.

And that's going to help speed the rate at which some of those peripheral

clocks adjust the new time zone.

It could be that we'll get more granular than that in the future as

we establish phase response curves.

But I think for now, that's a reasonable recommendation.

So, just to summarize, time shifter for light, nap, caffeine,

and melatonin schedules.

If you're going to use melatonin, you don't need a huge dose.

A lot of the literature has used doses of about three to five milligrams.

I actually think that you probably don't need a dose that's that high necessarily.

Just a milligram of melatonin or so is likely to do the trick and

most helpful if you're flying east.

And then for nutrition, pack high protein snacks that are familiar.

Easy to digest, concentrate your food intake at times when you would be eating

in both time zones, and after your first full night of sleep in a new time

zone, fully shift your food intake.

Another amazing answer.

What are your thoughts, I suppose, on melatonin as a general sleep

aid and sleep aids in general?

We discussed melatonin a lot in the last couple of minutes, and a

lot of people utilize it daily as a crush to help get them to sleep.

Obviously, that melatonin is a hormone.

It doesn't seem to have a negative feedback loop as say some of the sex

hormones do, but by sort of taking it exogenously or from external source,

you're still going to be interfering with your body's ability to potentially

produce it, at least in the short term.

Do you think it's something you should be taking daily or can take daily or?

Yeah.

And I suppose other compounds in that, in that same category.

So your, um, Your amino acids, your tryptophans that are sort of

augmenting or supporting the production of that same, that same hormone.

Do you think there's a place for those or should we really sort

of be trying to improve our sleep more through lifestyle means.

So I think in general, it makes sense to start with other things that are

often low hanging fruit that will more potently affect sleep issues

in the short term and the long term than melatonin Or nutraceuticals.

However, you can do both.

And I think that there are certain supplements that can

be helpful for sleep issues.

Melatonin is definitely one of them.

And, interestingly, if you look at how melatonin is prescribed, there's

one particular form that's given on prescription in the UK called circadian,

which is a time released formulation which is prescribed for older adults

with sleep maintenance issues.

So if they have insomnia symptoms where they struggle to maintain sleep during the

night, they might be prescribed circadian.

Sorry, is that a result of the, the odds you get potentially the less

melatonin you produce as a result of calcification of the pineal gland or

is that a bit of an old wives tale?

Yeah, I think that there's a lot more at play than that alone.

And melatonin, it does have some roles in sleep, but really it's more important

to the circadian system in general.

And there's a, there's a large array of different neuromodulators that are

involved in sleep and the different stages of sleep that we go through.

And chemically the brain is in very different states during different

stages of sleep, which is part of the reason why, honestly, I'm not

a huge fan of tryptophan or 5 HTP.

Because it could be The 5 HTP, for instance, is, is strongly

promoting serotonin synthesis, and serotonin in large part is a

weight promoting neuromodulator.

There are lots of nuances there.

Serotonin has many different receptors.

and the combination of different receptors that you agonize in different

parts of the brain is going to differentially affect sleep and stages

of sleep and wakefulness and so on.

But I'm not honestly a big fan of that particular strategy.

I do like that general approach where you're giving the body precursors for a

particular neuromodulator of interest and then there might be times when your body

is turning over and so on and so forth.

those chemicals faster, and therefore it uses that additional substrate to help

maintain levels of that neuromodulator at near optimal levels, and a good

example of that is using L tyrosine during periods of insufficient sleep

or total sleep deprivation to help maintain catecholaminergic signaling,

so levels of dopamine and noradrenaline specifically, and for that reason

L tyrosine can be quite helpful at maintaining certain cognitive functions

during sleep loss, but in the case of sleep I don't think that the data

regarding HTP are very compelling, but it's likely they do affect certain stages

of sleep more than others, and there are some interesting potential use cases.

So there's been some work relatively recently looking at 5 HTP in

Parkinson's disease, for example, and a lot of people with Parkinson's

have REM sleep behavior disorder.

It's kind of prodromal for Parkinson's and it could be that 5 HTP is

useful in that particular context.

But, going back to melatonin, while melatonin is used on prescription for

sleep maintenance issues in the UK, I actually think that regular melatonin is,

is really helpful, um, and more so than time release, but specifically for certain

circadian rhythm sleep wake disorders.

familial advanced, all familial delayed sleep phase syndrome where you

have these entire families of people with very late sleep timing, and you

want to shift their clocks earlier.

Melatonin can help with that.

Jet lag disorder.

Shift work disorder.

These are all instances where the system of clocks is disrupted,

either exogenously or endogenously, and melatonin can be helpful.

And like you say, there's not good evidence of that kind of inhibition

of melatonin synthesis by regular use.

It hasn't been that well studied, but right now there's not

really any evidence of that.

And in that way, as you said, it's very much unlike something like

taking testosterone, where quite quickly you will shut down your body's

own synthesis of the testosterone.

So that's interesting.

And looking at the long term safety of melatonin, it seems to be very good.

And there have been studies of various different clinical populations.

kids with autism, older adults with various different neurodegenerative

conditions, or people just with sleep issues, showing that

people can take moderate doses of melatonin for several years without

any obvious untoward effects.

And I think we're realizing with melatonin that while historically

it's been treated as a sleep hormone, it does a lot more than that.

It's important to circadian organization, obviously it's, it's potent antioxidant,

various different tissues, and now it's being studied therapeutically for uses

and everything from long COVID to PCOS, diabetes and various other things too.

So, so I am all for smart use of melatonin provided that it's.

used appropriately, it's sourced well as well, because I think the

reality is that a lot of people are sourcing their own melatonin.

And there have been these slightly esoteric studies where researchers will

take a bunch of melatonin from supplement shops and then test those products.

And then they find that the concentrations of melatonin range

from 80 percent less than to 480 percent more than what's on the label.

And some of them are contaminated with serotonin.

So you've got to be careful with the melatonin that you source.

And for that reason, I think in the right hands, it has its place, but it's

not something I would recommend to the masses, even if I think that for a lot

of people, it is likely to be beneficial.

I think with sleep supplements in general, so if you put aside drugs,

we need to bear in mind that a lot of these are acting on the same pathways

as drugs, and Some of them could produce tolerance and withdrawal effects over

time, theoretically, and so we need to use them in very targeted ways,

and we need to consider the totality of effects of the supplements.

And what I mean by that is, maybe, for instance, Someone is training

hard, and they're trying to build some muscle and burn some fat.

And their sleep is okay, but they've got some mild insomnia

issues, and they're a bit anxious.

For that person, something like ashwagandha is a really interesting

choice, because there's some evidence showing that it might slightly

speed the rate at which people build muscle and gain strength in

response to resistance training.

And also, of all the different supplements that have been studied, it's probably one

of the two best at lowering cortisol, at least when the cortisol has been sampled.

Whereas, you can take someone else who's got a completely different sleep issue.

So, take someone who has Restless Leg Syndrome, where they have this tingling

sensation that comes on in their limbs, and it's normally just the legs, but

for some people it's their arms as well.

It comes on shortly before sleep, and it makes getting to sleep really

hard, and it's really frustrating.

Often that's driven by insufficient iron in some parts of the brain.

And the way that that is therefore treated, is through iron supplementation.

So no one's speaking about iron as a sleep aid, but for that

person, iron is what they need.

That is the best sleep supplement they could possibly take.

For somebody else, something else is likely a better choice.

So you take the example of someone, I'll take it an unusual example,

someone doing an ultramarathon run.

They don't have enough time in which to sleep and they're running

for several days on the trot.

And they're experiencing massive amounts of muscle damage each day because some

of the running is downhill as well.

And they're going to carry all that stuff with them.

They therefore want to fall asleep quickly, have high quality sleep, and they

want something that's going to support the recovery of their muscles and connective

tissues between bouts of running.

For them, something like tart cherry juice is going to be a really good

choice because it's been shown to help with recovery from damaging exercise.

improve various different metrics of sleep quality.

And it's quite possibly slightly ergogenic in general, like it can promote

endurance performance in certain contexts.

So what I'm saying is you need to think about all of the effects of the product.

For me personally, I would never recommend anything that doesn't have good randomized

controlled clinical trials on it.

I'm talking about well conducted studies of humans and

therefore excellent safety data.

And if not, then you can just use common sense.

Tart cherry juice is going to be perfectly safe.

It's.

It's juice from cherries, like you, you don't need a long term safety

study of tart cherry juice or tomatoes would be another instance, but

for some things you do need that.

So think about all of these different variables that are at play and then be

meticulous about sourcing good products and look for products that have been

third party testing, which I know is something that you guys do at Vitality

Pro and I really commend you for that.

Yeah, very much.

That is definitely something that we.

Well, we sort of built our business upon, and it's something that we've

definitely noted in the industry.

As you mentioned earlier, uh, what is said on the label is oftentimes completely

wrong, whether it's the active ingredient in there is completely absent, or just

in there, the dose that is completely, um, what's the word I'm looking for?

Not reflective of, uh, of a clinically useful dosage.

Just before we go on, I'd just love to get your thoughts on other ways to sort

of promote sleep that don't necessarily utilize these sort of precursor molecules.

So, things like glycine and phosphatidylserine compounds that help to

sort of manipulate other systems in the body that can lower stress hormones such

as cortisol or lower body temperature.

Do you think those are an effective strategy, an effective tool?

Or again, is it very much context dependent?

Yeah,

I think it does come back to the sleep phenotype.

So what is this person presenting with?

What is their particular sleep issue?

And what's likely to be upstream of that?

However, I also think that there are certain things that a lot of people

who have sleep issues struggle with.

And so there are certain candidates that work really well for a lot of people.

And there are also supplements which might, based on the existing research,

be good for sleep in some contexts, but the research quality is quite weak

and there hasn't been that much of it.

However, if you look at the totality of research on the supplement, then

it seems to be a smart thing to add to your daily routine regardless.

And personally, I'd put glycine in that category.

I think glycine is a fascinating amino acid and it's come into the

spotlight in the last few years for its potential pro longevity effects.

It's one of a few supplements identified that's been studied in the ITP, the

interventions testing program that's been shown to extend lifespan of a particular

type of genetically diverse mouse and that's the gold standard way of Assessing

candidate longevity interventions in mammals at this point in time.

How Glycine is doing that.

We don't fully understand, frankly, and a lot of people think that that's to do

with some of its antioxidant and anti inflammatory actions, but surely it's

due to a diversity of different actions.

In the case of sleep, the existing clinical trials I don't

find particularly compelling.

They're small, they're underpowered, and with that said, they, they have

so far shown some positive effects on sleep quality, quality and next

day cognitive function too, during periods of insufficient sleep.

And then As you're alluding to mechanistically, some of that seems

to relate to glycine affecting neuromodulation at the master clock in

the brain, and then in turn affecting regulation of body temperature

by facilitating distal heat loss.

So for me, I look at glycine and I think, is it something that's

going to be a potent sleep aid?

I don't know.

Probably not.

I think it's going to mildly improve sleep in many people, probably

won't improve sleep in everyone.

Is it something that most people benefit from consuming more of?

Yes, I think it absolutely is.

And so, for me, it's one of not that many ingredients where I

give it a thumbs up regardless.

Because most people have a kind of glycine gap where the total amount

of glycine they consume each day is probably insufficient to meet their

metabolic needs at certain times.

Some people would define it as a conditionally essential amino acid.

Sorry, Rob, for what you're going to say.

Yeah, I was just going to say, especially when you look at how sort of dominant

people's diets are in terms of methionine content, you oftentimes get a pretty

stark sort of drop off in glycine, which is again going to then, yeah, result in,

inability among other things to, yeah, uh, regulate that sort of not traumatic.

And yeah, your body's ability to sort of regulate temperature in the evening.

Yeah.

So, so I think, I think glycine is a, is a good supplement

for a lot of people to take.

And I think we need more research on its effects on sleep specifically, but I'd

feel relatively comfortable saying that if most people add three to five grams,

a day to their diet, that's a good move.

And a lot of people will be adding that anyway by taking

10 grams of collagen powder.

Collagen is about 30 percent glycine on average.

And interestingly, there has actually been a study in the last year or

so showing that when people consume collagen late in the day, they do see a

small improvement in some sleep health metrics, which the authors chalked

up to the collagen's glycine content.

And mechanistically, mechanistically that does make some sense.

Regarding phosphatidylserine, I'm not, I'm not a big fan, to be honest.

I don't find the research particularly compelling.

I think it's, it's perfectly safe.

I think it's, it's an interesting adjunct intervention in particular

for some older people who might be experiencing mild cognitive impairment.

I think that some particular types of phosphatidylserine might be slightly

good for brain health in general because of their incorporation into the brain.

So membranes, there haven't been any good clinical trials

showing any effects on sleep.

Does it affect people's stress responses to things?

Again, the jury is somewhat out.

A lot of the early work looked at exercise training and whether it influenced

things like cortisol and noradrenaline and adrenaline responses to exercise.

And some of those studies showed that it did somewhat diminish

those stress hormone responses.

Thank you But others didn't find that.

So, the literature is relatively inconsistent.

I think the form does matter in this instance.

And again, I think that for brain health in general, it's, it's probably weakly

beneficial for a lot of people, but there are other candidate ingredients

that I find much more interesting.

And if we were focusing on how stress specifically might affect sleep, then

there are things that I would reach for much sooner than phosphatidylserine.

I've actually never recommended phosphatidylserine to someone, not

phosphatidylserine specifically, but in the case of stress related sleep

issues, I think L theanine is a good candidate because It has an excellent

safety profile, as far as we can tell.

It's something that's part of the human diet anyway, by way of consuming tea.

It's also present in small amounts in some mushrooms.

And if you look at the research on L theanine and different forms of

psychological distress that people are experiencing, It quite consistently

has a small positive effect on how people feel in response to stress.

And it hasn't been that well studied in this context, but

it, it, it might mildly reduce.

people's stress hormone responses as well.

And there have been a few studies, and there's one good one in

particular showing that L theanine can improve some sleep metrics, in

particular rates of sleep quality.

And then if you look at all of the effects of L theanine, it's probably

weakly good for cardiovascular health.

It also seems to affect a subset of immune cells in a way that's

probably beneficial for most people.

So, given the safety data, and given all of the effects of L theanine, including

those on cognitive function too, because a lot of people take it early in the

day with caffeine, and relates to that, and this actually is something that is

really underappreciated, and it might be the biggest benefit of L theanine.

L theanine might slightly offset the adverse effects of caffeine on sleep.

And so in a society where a lot of us are mainlining caffeine, if

there's something that you can take that's good for you in general.

and it slightly diminishes the effects of caffeine on your sleep.

That's an easy win.

And that's where L theanine comes in.

And then I mentioned ashwagandha earlier, and ashwagandha is interesting as

something that can perhaps slightly more potently affect cortisol specifically.

It also seems to have some effects on some of the sex steroids.

So quite consistently increases testosterone in men.

the magnitude of that increase over time seems to be something like 10 to 15

percent from other people, but ashwagandha is a very promiscuous molecule.

It seems to affect lots of different targets and there are some minor

concerns related to some case studies that reported liver issues after taking

certain types of ashwagandha extracts.

Again, I think the form matters.

I think we need more research on that specifically because it's just

a series of individual reports.

where people have experienced liver issues, but with ashwagandha it's

definitely something that I would cycle.

I wouldn't have any reservation saying that someone could take

glycine or l theanine in modest doses, probably indefinitely,

without any issues whatsoever regarding toxicity or what have you.

That is not the case for ashwagandha and I probably wouldn't recommend

that someone takes ashwagandha for longer than about a week.

16 weeks at a time at the upper end of the range.

A lot of the studies are 8 to 12 weeks.

So I think 12 weeks is an appropriate period of use before you take

a similar amount of time off.

Yeah, no, I think you're completely right.

Adaptogens in general need to be cycled.

Just with regarding tolerance and some of these amino acids, do you

think those need to be cycled?

Uh, again, your, uh, your compounds like your L thene and your glycine, especially

for their sort of, uh, psychoactive properties, are you going to develop

a tolerance to some of these compounds do you think or less so than maybe your

precursors like again, 5 HTP, et cetera?

I think less so than something like 5 HTP or L tyrosine where there's clearly

A known metabolic pathway and you're providing a precursor within that

pathway, which has been shown to in some instances quite potently affect

levels of an intermediary of interest like serotonin in the case of 5 HTP

or dopamine in the case of L tyrosine.

So, while they are amino acids, and they're influencing levels

of certain neuromodulators.

I don't think that glycine intake or taurine intake, say, are as

big concerns as those others.

Should people therefore cycle them?

I think some of this relates to, to your personal risk tolerance.

I personally, and I, I'm, I'm quite, I would say that I'm, I'm relatively

particular about not taking things for extended periods if there are

any safety concerns whatsoever.

I wouldn't personally, based on the literature that I've seen, have any

reservation about taking glycine, taurine, L theanine in the long term.

I would, taking 5 HTP or L tyrosine, or possibly tryptophan as well.

So I think you need to take it on an ingredient by ingredient basis.

But the reality is that we don't have those long term intervention

studies that will give us that information about whether certain

pathways are downregulated.

And whether that is a concern and therefore these

things do need to be cycled.

But looking at the existing literature, I think that we do know

something about the safety of a lot of these different substances.

And there are bigger questions regarding some of them, like 5

HTP or ashwagandha, than there are concerning others like L theanine.

or glycine and obviously dose is really important here too.

So in the case of glycine, if you look at some of the research on glycine, a lot

of it, the majority of, and this probably isn't appreciated because I think in a

lot of podcasts, people just think, Oh, glycine is that great sleep supplement.

You've got to take three grams an hour before bed.

And then that will sort your sleep issues.

And that's what most of the research has shown.

Most of the research on glycine has been on psychiatric patients.

And a lot of it has used very, very high doses and using glycine in that way.

That is probably an intervention that needs to be cycled,

those types of high doses.

3 grams of glycine, however, you get that from 10 grams of collagen, which you might

consume by way of gnawing on the ends of your chicken bones at dinner each day.

Would you be concerned about the 3 grams of glycine you get from that food matrix?

No, you wouldn't.

It's within the realms of what you'll get from your diet anyway.

So, you contrast that with taking a large dose of 5 HTP.

Would you get that from your diet?

Maybe if you're eating a very large dose of certain plants?

But, but probably not.

So, I think we also just need to, to consider what's, what's normal

in the context of, of the human diet and, and absent specific studies,

think about what might make sense.

I think a lot of this is just common sense.

Three grams of glycine, I'm not personally concerned.

100 milligrams of L theanine, not at all concerned.

You know, that's a couple of cups of green tea.

400 milligrams of L theanine, I start thinking about it.

200 milligrams of L theanine, probably fine.

So the dose makes the poison.

Yeah, definitely.

I think, as you said, it just comes down to common sense.

And there's definitely nothing in my, what's your, uh, saying?

There's no free lunch in biology.

Uh, the moment you start, uh, moving one metric, you're gonna move another,

and you're gonna skew amino acid profiles and create all sorts of

imbalances upstream that can cause neurotransmitter issues potentially.

Um, so, yeah, no, I couldn't agree more.

Greg, I want to be respectful of your, of your time and thank you for it.

I, I've definitely learned a lot.

And, um, that's something I often say, but this time round, I really mean it.

So thank you.

Where's the best place people can find you at the moment?

You seem to be involved in a lot, but, uh, for you, what

is your lowest com, If you're

listening to this, then you must like podcasts.

And last year I started my own podcast, which is Reason and Wellbeing.

So if you're interested in health and performance and critical

thinking, then you might enjoy that.

So that's Reason and Wellbeing.

And there's also a YouTube channel, which is Ackroyd Potter PhD.

It's the same handle that I use for Instagram and Twitter.

People want to follow me there, but the podcast episodes go up on YouTube as well,

and I'll probably add some additional content to the YouTube channel over time.

So I'd probably funnel people in that direction.

But yeah, if you do check out the podcast and let me know your

thoughts and do feel free to send me spam via Instagram as well.

And if I like your spam, I'll respond.

And if I don't, then I won't.

Fair enough.

Well, thanks a lot.

I really do or we really do appreciate it.

And yeah, we'll have to do this again soon.

But yeah, thanks a lot.