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- Welcome to the Huberman Lab Podcast,
where we discuss science
and science-based tools
for everyday life.
[upbeat music]
I'm Andrew Huberman,
and I'm a professor of
neurobiology and ophthalmology
at Stanford School of Medicine.
Today, my guest is Dr. Rhonda Patrick.
Dr. Patrick is known to
some of you as a podcaster
and one of the premier educators
in the landscape of
mitochondria, metabolism, stress,
and other aspects of
brain and body health.
Her podcast, FoundMyFitness,
is one of the premier
podcasts in the world
for disseminating knowledge
about how the brain and body work
and how we can use behavioral
tools, micronutrients,
supplements and other protocols
in order to maximize our
immediate and long-term health.
Dr. Patrick did her formal
training in cell biology,
exploring the links between
mitochondrial metabolism,
apoptosis, which is naturally
occurring cell death,
which is a healthy form of cell death
that occurs in our brain and
body throughout the lifespan,
and cancer biology.
She then went on to do
postdoctoral training
with Dr. Bruce Ames,
investigating the effects
of micronutrients,
meaning vitamins and minerals,
and how they affect
metabolism, inflammation,
DNA damage, and the aging process.
She has published landmark review articles
and primary research,
meaning original research articles,
in some of the premier
journals in the world,
including Science, Nature Cell Biology,
Trends in Cell Biology, and FASEB.
Indeed, Dr. Patrick is an expert
in an extraordinarily
broad range of topics
that impact our health.
For today's episode, we focus primarily
on the major categories of micronutrients
that are essential for
brain and body health.
I have to confess that
before the discussion
with Dr. Patrick,
I was aware of only one of the categories
of micronutrients that we discuss,
and so you'll notice that
I'm wrapped with attention
throughout the discussion.
And I think that you'll want
to have a pen and paper handy
because she offers not only
a very clear understanding
of the biological mechanisms
by which other micronutrients operate,
but some very clear and
actionable tools and items
that we can all embark on
if we are to optimize our
brain and body health.
We also discuss behavioral protocols.
Dr. Patrick is well known
for her understanding
of the scientific literature on sauna
and the use of heat and
cold for optimizing things
like metabolism, longevity,
cardiovascular health,
and I'm delighted to say
that we discus that as well,
and how behavioral protocols can interface
with supplement-based and
nutritional protocols.
I'm confident that you'll
learn a tremendous amount
of information from Dr. Patrick,
much of which is immediately actionable.
And if you're not already
following and listening
to her excellent podcast, you'll
absolutely want to do that.
It's foundmyfitness.com is the website
where you can get access to that podcast.
It's also on Apple and Spotify
and YouTube as FoundMyFitness.
Dr. Patrick also has a terrific newsletter
that I recommend signing up for.
It's foundmyfitness.com/newsletter
is where you'll find it,
and it includes research
on fasting, micronutrients,
sleep, depression, fitness,
longevity, and far more,
along, of course, with
actionable protocols.
I'm pleased to announce that
the Huberman Lab Podcast
is now partnered with
Momentous supplements.
Our motivation for
partnering with Momentous
is to provide people one
location where they can go
to access the highest quality supplements
in the specific dosages
that are best supported
by the scientific research
and that are discussed
during various episodes
of the Huberman Lab Podcast.
If you go to livemomentus.com/huberman,
you will see those formulations.
I should mention that we are going to add
more formulations in the months to come.
And you'll see specific suggestions
about how best to take those supplements,
meaning what dosages and times of day,
and, in fact, how to
combine those supplements
with specific behavioral protocols
that have been discussed on the podcast
and are science supported
in order to drive the maximum benefit
from those supplements.
And many of you will probably
also be pleased to learn
that Momentous ships not
just within the United States
but also internationally.
So, once again, if you go to
livemomentus.com/huberman,
you'll find what we firmly believe
to be the best quality supplements
in the precise dosages
and the best protocols for
taking those supplements
along with the ideal behavioral protocols
to combine with those
supplement formulations.
I'm pleased to announce that
I'm hosting two live events
this May.
The first live event will be hosted
in Seattle, Washington, on May 17th.
The second live event will be hosted
in Portland, Oregon, on May 18th.
Both are part of a lecture series
entitled "The Brain Body Contract,"
during which I will discuss
science and science-based tools
for mental health, physical
health, and performance.
I should point out that,
while some of the material
I'll cover will overlap
with information covered here
on the Huberman Lab Podcast
and on various social media posts,
most of the information I will
cover is going to be distinct
from information covered on
the podcast or elsewhere.
So, once again, it's Seattle on May 17th,
Portland on May 18th.
You can access tickets by
going to hubermanlab.com/tour,
and I hope to see you there.
Before we begin, I'd like to
emphasize that this podcast
is separate from my teaching
and research roles at Stanford.
It is, however, part
of my desire and effort
to bring zero cost to consumer information
about science and science-related tools
to the general public.
In keeping with that theme,
I'd like to thank the
sponsors of today's podcast.
Our first sponsor is Athletic Greens.
Athletic Greens is an all-in-one,
vitamin mineral probiotic drink.
I've been taking Athletic
Greens since 2012,
so I'm delighted that they're
sponsoring the podcast.
The reason I started
taking Athletic Greens,
and the reason I still
take Athletic Greens
once or twice a day,
is that it helps me cover all
of my basic nutritional needs.
It makes up for any
deficiencies that I might have.
In addition, it has probiotics
which are vital for microbiome health.
I've done a couple of episodes now
on the so-called gut microbiome
and the ways in which
the microbiome interacts
with your immune system, with
your brain to regulate mood
and essentially with
every biological system
relevant to health throughout
your brain and body.
With Athletic Greens, I
get the vitamins I need,
the minerals I need,
and the probiotics to
support my microbiome.
If you'd like to try Athletic Greens,
you can go to athleticgreens.com/huberman
and claim a special offer.
They'll give you five free travel packs,
which make it easy to
mix up Athletic Greens
while you're on the road,
plus a year's supply of vitamin D3 K2.
There are a ton of data now showing
that vitamin D is essential
for various aspects of
our brain and body health.
Even if we're getting a lot of sunshine,
many of us are still
deficient in vitamin D3.
And K2 is also important
because it regulates things
like cardiovascular function,
calcium in the body, and so on.
Again, go to athleticgreens.com/huberman
to claim the special offer
of the five free travel packs
and the year's supply of vitamin D3 K2.
Today's episode is also
brought to us by Thesis.
Thesis makes what are called nootropics,
which means smart drugs.
Now, to be honest, I am not
a fan of the term nootropics.
I don't believe in smart drugs
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I do believe, based on science, however,
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Today's episode is also
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And now for my discussion
with Dr. Rhonda Patrick.
Rhonda, welcome.
This has been a long time coming.
Even longer than you know
because, even before we discussed
you coming on this podcast as a guest,
I've been watching your
content for a very long time.
So I want to start off
by saying thank you.
You were the spearhead to break through
from academic science to public education.
So I consider you first in,
and the rest of us are just in your wake.
So, thank you for that. It's been-
- Oh, that is so kind.
Thank you. Thank you so much.
Well, it's absolutely true.
- I am so excited to be here
having a conversation with you.
- Thank you.
It's absolutely true.
If anyone does their
research, they'll realize
that the statement I just
made is absolutely true
and there isn't even a close second.
Any other public facing educators
that have formal science training
and do regular posting of content
came in several years
after you initiated it,
so we're all grateful.
I have so many questions,
but I want to start off
with kind of a new but old theme
that you're very familiar with.
So temperature is a powerful stimulus,
as we know, for biology,
and you've covered a lot of material
related to the utility of cold
but also the utility of heat,
and, as I learn more and
more from your content
and from the various papers,
it seems that there's a bit of a conundrum
in that cold can stimulate
a number of things,
like increases in metabolism, brown fat,
et cetera, et cetera.
Hopefully, you'll tell
us more about those.
But heat seems to be able to
do a lot of the same things.
And I wonder whether or
not the discomfort of cold,
deliberate cold exposure,
and the discomfort of heat
might be anchoring to the same pathway.
So, would you mind sharing with us
a little bit about what happens
when we get into a cold
environment on purpose,
and what happens when we get
into a hot environment on purpose?
And I'm hoping that this
might eventually lead us
to some point of convergent
understanding, so if you would.
- I would love to. Let's take a step back.
I think you brought up a
really important point here.
And I think that point
has to do with the intermittent
challenging of yourself
and whether that is through
temperature changes,
like cold or heat,
or through other types of
stressors, like physical activity,
or perhaps even dietary compounds
that are found in plants.
These are things like
polyphenols or flavanols.
Humans, we evolved to
intermittently challenge ourselves.
And before we had Instacart,
where you could basically
just get your food delivered to you,
before the Industrial Revolution occurred,
we were out hunting.
And I say, we, not us but humans.
We were out gathering.
We were moving, and we
had to be physically fit.
You couldn't catch your prey
if you were a sedentary slob, right?
You were moving, and you
had to pick your berries.
You had to move.
And so physical activity
was a part of everyday life,
and caloric restriction
or intermittent fasting
was also a part of it.
This is another type of challenge.
We didn't always have
a prey that we caught,
or maybe temperatures were
such that there was nothing
for us to gather, right?
So food scarcity was something common
as well as eating plants,
so getting these compounds
that I mentioned.
These are all types of stress,
intermittent challenges,
that activate genetic
pathways in our bodies.
These are often referred to in science
as stress response pathways
because they respond to
a little bit of stress.
Physical activity is strenuous.
Fasting's a little bit
stressful. Heat, cold.
These things are all types
of little intermittent challenges.
And there is a lot of crosstalk
between these stressors
and the genetic pathways
that they activate.
And these genetic pathways
that are activated
help you deal with stress.
And they do it in a way
that is not only beneficial
to help you deal with
that little stressor,
exercise or heat,
it stays active, and it helps
you deal with the stress
of normal metabolism, normal
immune function happening,
just life, aging, right?
So this concept is
referred to as hormesis.
This is a little bit
of stressful challenge
that activates these
stress response pathways
in a beneficial way,
that is a net positive,
that actually has a very
profound antioxidant,
anti-inflammatory response,
or whatever the response is.
It could be the production
of more stem cells.
These are cells that help regenerate
different cells within tissues,
or something like autophagy,
which is a process that can clear away
all the gunk inside of our cells,
pieces of DNA, protein aggregates.
So you'll find that the
stress response pathways
are activated by a variety of stressors.
So, for example, one pathway
is called heat shock proteins,
and, as their name would
imply, one would go,
"Oh, they're activated by heat."
Well, correct. They are
activated very robustly by heat.
And we can talk about that.
You can eat a plant like broccoli sprouts,
which is high in something
called sulforaphane.
This is a compound that is sort
of like a hormetic compound,
or, as David Sinclair likes to say,
it's a xenohormetic compound.
I love that. I love that term.
And it activates heat shock
proteins among other things.
It also activates a very
powerful detoxification pathway
called Nrf2, which helps
you detoxify things
like carcinogens that you're exposed to.
Well, guess what? Heat activates that.
So what I'm getting at
is there is overlap.
Cold also activates heat shock proteins.
You're like, "Really?
Cold?" Yes, it activates.
These are stress response pathways,
and they are activated by
various types of stressors.
Now, you're going to more robustly
activate heat shock proteins
from heat versus cold,
but there is some overlap.
So I think that sort of
forms the foundation there.
- Yeah, that's very helpful.
And it brings to mind, in the
context of the nervous system,
I always tell people you
only have a small kit
of neurochemicals to work with.
There isn't dopamine for Netflix,
and then dopamine for relationship,
and dopamine for work, et cetera.
Dopamine is a generic pathway
by which motivation, craving,
and pursuit emerge, et cetera,
just like adrenaline is a generic theme
of many different behaviors.
It seems that it is the
job of biological systems
to be able to take a
diverse range of inputs,
even unknown inputs.
Like, we don't know what technology
will look like in three years,
but you can bet that some
of those novel technologies
will tap into the very systems
that I'm talking about now.
And there certainly will be
other stressors to come about
that will tap into these pathways.
I have two questions related
to what you just said
before we talk a little bit
more about cold and heat.
You mentioned plants as a route
to creating intermittent challenge.
There's a lot of debate, mostly online,
about whether or not
plants are our friends
or plants are trying to kill us.
The extreme version from
the carnivore types,
pure carnivore diet types,
is that plants are trying to kill us.
From the plant-based diet folks,
it seems like it's more
about what's healthy
for the planet, animals, and maybe for us.
But, if we set aside that argument,
and we just raise the hypothesis
that plants have compounds
that are bad for us,
but maybe by consuming
them in small amounts,
they're creating this
hormesis type scenario,
so then I think we
conceivably solve the problem.
We could say, yes, plants are bad for us,
but, in small amounts, they
provide this hormetic response
and they're good for us, right?
So, in the same way that
too much heat is bad for us,
too much cold is bad for us,
can kill us, can kill neurons,
but, appropriately dosed,
in an intermittent
challenge type of scenario,
it can be good for us.
Is that how I should think about
plants and these compounds?
Do you think of them as good
for us or as bad for us?
They're a very sharp blade, and
we want to use them potently.
- I actually think that
it's almost impossible.
I mean, you'd have to eat nothing
but the same plant all
day, every day in large.
The bioavailability of these
compounds in the plants,
they're attached to a food matrix.
It's not like taking it in
a supplement form as well.
It's such that it's very
difficult to make it toxic.
Now, there are some cases,
for example, if you eat cabbage,
and I think there's some
group in Africa or somewhere
that that's all they eat is cabbage,
and there is a goitrogen in cabbage.
It's not sulforaphane.
It's another compound.
But that's all they eat,
every day. Nothing but that.
- They get goiter. The thick neck.
- Yeah, and they're iodine
deficient on top of that.
So I do think,
you can, of course, make.
I mean, there are types
of plants that are toxic
in small quantities, right?
- Hemlock.
- [Rhonda] Hemlock, exactly.
- Will kill you.
Folks, don't play this game with hemlock.
- But you're not going to get poisoned
from eating your serving of
broccoli at dinner, right?
So, I mean, it depends on the plant.
These generalizations are kind of,
they're just not useful,
and I think that a lot of people
online in the blogosphere,
they gravitate towards them
because it's just easier,
and it's a lot more sensational.
- I eat plants, meat, and starches.
I'm one of those rare
omnivores out there now.
- I do, too.
- I feel like it's rare to be an omnivore.
But I think, once you step
out of the social media,
as you said, the blogosphere,
most people, I would say,
99% of people on the planet
are probably omnivores.
- Right.
- And someone will probably correct me,
but I doubt the number falls below 98.
- I think, if you look at data,
and when we have carnivore
data, I can't wait to see it,
but, right now, it's a lot of,
okay, well, this is a lot
of anecdotal evidence,
and there's a lot of good
starts with anecdotes,
but people change a
thousand things at once,
and they don't realize that, but they do.
And so anecdotal data
is only so good, right?
It's a starting point.
And so we don't really know long-term
what carnivore diets are going to do.
They may be beneficial short-term.
They may be beneficial for reasons
of elimination of other things.
Who knows, right? Lots of possibilities.
But I do think, with respect to plants,
that there's so much evidence,
like, for example, sulforaphane
is one that I really like
because there's just
evidence that sulforaphane
is a very powerful activator
of the Nrf2 pathway.
And this is a pathway that
regulates a lot of genes,
a lot of genes that are related
to glutathione production,
genes that are involved
in detoxifying compounds
that we're exposed to from our food,
like heterocyclic amines.
In fact, there have been GWAS studies.
These are studies that are
genome-wide associated studies,
for people listening that aren't familiar.
People have a variety
of versions of genes,
and we have a gene that's able
to make heterocyclic amines
to basically detoxify it
so it's not as harmful.
And people that don't have
a certain version of that
that's doing it well
are very prone to colon cancer
and increased cancer risk,
but if they eat a lot of broccoli
and cruciferous vegetables,
that negates that risk
because they're getting sulforaphane,
which activates a lot of
the glutathione transferase
and synthase genes.
So glutathione's a major
antioxidant in our brain,
in our vascular system,
in our body, basically.
So there's evidence that
eating things like compounds
that are like sulforaphane or
broccoli or broccoli spouts,
which have up to 100
times more sulforaphane
than broccoli, are activating
glutathione in the brain.
There's human evidence of that.
I mean, that's amazing.
- [Andrew] That is amazing.
- In Plasma. Yeah.
- Sorry to interrupt. I
just want to make sure.
So broccoli sprouts are
different than broccoli,
and you just told us
that they're much richer
in these compounds.
So, note to self, I should
have broccoli sprouts,
not just broccoli.
Can we cook the broccoli and
still get these nutrients,
or do we have to eat it raw?
I confess, eating raw broccoli
is really aversive to me.
- So the sulforaphane is formed
from a compound called glucoraphanin,
which is in the broccoli,
and the enzyme that
converted into sulforaphane
is myrosinase, and it's heat sensitive.
So you do somewhat lower
the sulforaphane levels
when you cook the broccoli.
However, there was a
study a few years back
that showed adding one gram
of mustard seed powder,
ground mustard seed powder,
which also contains the myrosinase enzyme,
to your cooked broccoli
increases the sulforaphane
by fourfold, so...
- This is great 'cause, I confess,
I like broccoli if it's cooked
to the appropriate density,
not too mushy but definitely not raw.
The idea of eating raw broccoli
to me just sounds horrible,
but I like the way mustard seed sounds.
So just a little bit
of mustard seed powder
added to the cooked broccoli
can recover some of these compounds.
- Yes, so what I do is I will
lightly steam my broccoli,
and then I add a little
bit of my Kerrygold butter,
and then I add some mustard
seed powder on the top of that.
And it's got a little kick.
It's just a little spice.
And if you don't taste that, it's expired.
It should have a little kick.
- And because I know
people will want to know
how often and how much,
are you eating this every
day or most days of the week?
- Well, I had shifted to
supplementation with sulforaphane.
I'm admitting right now that
I've been terrible about it
the past, I don't know, six months or so.
- The supplementation
or the broccoli?
- Yes, the supplementation.
And so there's another way to get.
There's another compound,
and it's actually called moringa.
And Dr. Jed Fahey, who's really
the expert on sulforaphane.
He's a good friend of mine.
He's been on the podcast
a couple of times.
He basically thinks,
and has done a lot of
research on marina as well,
that it's like the cousin,
and it activates the Nrf2 pathways
similarly to sulforaphane.
And so I've been buying this
Kuli Kuli moringa powder.
I don't have any affiliation with him.
- Kuli Kuli is a brand?
- Kuli Kuli's the brand.
- That you have no affiliation to.
- I have no affiliation, but
Jed Fahey has researched it,
like that specific
brand, and so it's legit.
It's science backed
in terms of actually containing
moringa and activating Nrf2.
And I add it to my smoothies.
So that's what I've been doing.
- What are some dose ranges?
And, of course, we give
the usual recommendations
that people should talk
to their physician,
et cetera, et cetera.
But, if people are going
to, what do you take?
That's always the...
- A big, heaping tablespoon.
- Let's take
the David Sinclairian approach,
where he'll talk about what he does,
as a way to deal with this.
Of course, everybody's different
and should, in all seriousness,
anytime you add or delete
something from your consumption
should consult some trusted
healthcare professional,
trusted by you.
Do you recall the dosages?
- I do a big, heaping tablespoon.
- So Kuli Kuli moringa.
It sounds like a song.
- It's with a K. I know, it does.
But, for people also listening,
it's like, "Well, why would I do that?"
I mentioned the glutathione in the brain.
I mentioned it in plasma.
It's been shown to lower
DNA damage in people,
in white blood cells.
There's been several
different studies in China.
In China, there's a lot of air pollution.
And I mentioned that it's a
very powerful activator of Nrf2.
And I know you're familiar with Nrf2.
Nrf2 is a transcription factor that is,
it is binding to a
little specific sequence
in a variety of different
genes, and it's turning them on,
or, in some cases, turning them off.
It's regulating what's being activated
or what's not being
activated, being turned off.
And some of the genes are basically
these detoxifying pathways.
We talked a little bit
about the glutathione,
but there's also ones that are involved
in airborne carcinogens, like benzene.
So benzene's found in air pollution.
I mean, cigarette smoke.
If you're smoking cigarettes
still, please try to quit.
- Yeah, you're mutating your DNA.
- [Rhonda] Yeah, it's the worst.
- To say nothing of the lung cancer,
you're mutating your DNA.
- And heart disease
risk. Heart disease risk.
But, anyways.
People, and this has been
repeated in more than one study,
that literally after 24 hours of taking,
I can't remember off the top of my head
what the dose of sulforaphane
from broccoli extract,
broccoli seed extract was,
or broccoli sprouts extract, not the seed.
It was the sprouts.
Anyways, they started excreting
60% benzene and acrolein.
That's something that
we get in cooked food.
- It's coming out in their urine?
- Coming out in their urine. Yeah.
- Well, I'm not a smoker,
and I have to be honest.
It's rare that I hear of a
supplement for the first time
'cause I've been
deep-diving on supplements
since I was in my teens.
This is fascinating,
and it brings back to this
question that we had before,
and I appreciate that you've
answered it very clearly.
Plants have compounds
that are good for us.
They're not just stressing us.
They're activating pathways
that are reparative.
That's what I'm taking away
from everything you're telling me.
- Right, and that our bodies,
we're supposed to be getting that stress
to have those pathways activated.
You know, right?
I mean, this is conserved
among different animals.
This is something that is,
it's supposed to happen.
And, in our modern day world,
we don't have to eat plants.
We don't have to move
anywhere or exercise.
We don't have to go through
periods of not eating food
because we can have it at our fingertips
at any second, right?
So, I mean, we've got this conundrum of,
we're never activating these
stress response pathways
that we're supposed to activate.
We're supposed to.
- I find that fascinating, and again,
drawing a parallel to the nervous system,
so what I'm hearing you
say is that, historically,
we would have to go through some stress,
some confront cold or confront heat,
or confront effort or hunger,
have to exercise, essentially,
in order to obtain these compounds,
and then those compounds are reparative.
Yeah, I feel that resembles
the dopamine pathway.
I always say there's
nothing wrong with dopamine.
People think about dopamine
hits as bad or dopamine is bad.
There's absolutely nothing
wrong with dopamine.
The problem is dopamine,
especially high levels of dopamine,
released without the need for
effort to access that dopamine
is problematic.
So a line of cocaine gives
you a ton of dopamine
with no effort except to ingest the drug,
whereas working for four years
or more to get your degree
will release a lot of dopamine
and a lot of cortisol
along the way, as we know,
and it's considered a healthy
accomplishment in most cases,
a tremendous amount.
We're approaching the spring,
and there'll be a lot of graduations.
Weddings are coming up
now that the pandemic
is hopefully slowing.
And there'll be a lot of dopamine.
High levels of dopamine are great,
but only after the effort
of having done something
in order to access it.
And so that's what I'm taking
away from what you're saying
is that we need to go
through this intermittent,
different types of intermittent challenge,
and we are rewarded with
particular compounds
that are reparative,
both for the challenge,
but then make us stronger.
Hormesis really is, it seems,
a case of what doesn't
kill us, makes us stronger.
So you mentioned-
- Can I add to that
one thing you just said?
- [Andrew] Please, please.
- Because this has been shown
with, for example,
sulforaphane in animal studies,
you precondition, give
the animal sulforaphane,
and then you expose them to hypoxia
or some kind of ischemic stroke condition,
whatever they do to induce that,
and the sulforaphane, it
basically protects them.
Their precondition
and their stress response
pathways are primed,
and so, when they're then
exposed to the ischemic stroke,
their outcomes are so much
better, so much better
than the animals that
didn't get the sulforaphane
48 hours before or whatever it was.
And this has been shown
in multiple animal studies
with sulforaphane
specifically in the brain.
I know Mark Mattson. Dr Mark Mattson.
He's often thought of as the
intermittent fasting king,
but he's a neuroscientist,
and he did publish some work
and talks about sulforaphane as well.
- I'm really glad you brought
that up, that example up,
because many of the questions
I get on social media
and elsewhere are about
traumatic brain injury.
And TBI is just one example.
And people always think,
"Oh, sports. It's football."
Whenever you say TBI, people
always think football.
And I just want to just take
a moment to editorialize.
90% or more of traumatic brain injury
is construction work, at-home accidents.
Football players, hockey
players, martial artists
are a tiny fraction of
the people who have TBI
and concussion of various kinds.
It just so happens that,
within those communities,
many of them, 75% or
more, experience those.
So it's salient within those communities,
but concussion is prominent.
People are always asking, "What can I do
"in order to offset brain injury?
"I had a concussion two
years ago. What can I do?"
And it's been a tough question
because we really don't
have anything for them.
I mean, you tell them sleep
well, eat well, exercise,
but it sounds like some of
these reparative pathways
either should be explored in
the context of brain injury
or, I'm guessing, are being explored
in the context of brain injury.
- Yeah, so a couple of things there.
One is that, I mean,
traumatic brain injury,
it's terrible, but it's so interesting
because it's also like
literal, real-time brain aging.
You're able to accelerate
it and understand.
So I often think of, when I
think of traumatic brain injury,
I think of so much overlap
between Alzheimer's disease
and dementia and these
neurodegenerative diseases
because there are a lot
of similarities there.
And so, sulforaphane, I personally think,
and I do think there's
been some animal research
with TBI and sulforaphane,
mostly preconditioning
rather than treatment.
So, again, it's like, well,
if you want a healthy lifestyle thing
and you're a construction worker,
or you're fill in the
blank, that's going to.
I mean, anyone that drives a car,
you're at risk to some degree, right?
- [Andrew] Or bicycle.
- Bicycle, yeah.
- Around Stanford, I would say
people demonize motorcycles,
people demonize a lot of things,
but moving fast through
space on a small object
next to a 3,000 pound vehicle,
I mean, we have a number
of friends that have died.
We have a number of people
with traumatic brain injury.
I'm not against cycling or cyclists,
but it's a risky sport by any stretch.
So, in taking things like moringa
or eating my broccoli sprouts,
maybe cooking them a little less
than I'm currently cooking them,
putting on the mustard seed.
Is there evidence that?
Well, first of all, Nrf2
is expressed in neurons,
so those cells should be protected.
Are there other cells of the body
that could possibly gain
protection from these pathways?
- Well, lungs for one, but
just even in plasma cells.
I think Nrf2 is pretty
ubiquitously expressed.
Liver.
There's so many animal studies
that have looked at all those things.
I try to kind of gravitate
towards human ones
'cause it's a lot more relevant.
But I think, overall, like I mentioned,
DNA damage lower.
It was like 24 or 34%
lower in human blood cells
after broccoli sprout
powder supplementation.
- [Andrew] Wow.
- And I made a video on
this years ago, 2016 maybe,
and I think I have the references
on there to exact amounts.
I can't remember.
- We can link to the video.
- But it's kind of an
old video. It's 2016.
But I also had Jed on the podcast,
and he did talk about this.
But it's also been shown in
randomized controlled trials
to help treat autism
and autistic symptoms.
Yet again, it's doing
interesting things in the brain,
and I think it does have something to do
with the oxidative
stress, the glutathione,
which would be relevant for TBI treatment.
It hasn't been shown empirically
that that helps with treatment,
but I do think someone
could do that study.
I think that it should be done, honestly,
because it's a low-hanging fruit,
I mean, if there's any impact.
And there is at least
one preliminary study
that glutathione is increased in the brain
after humans are basically
taking sulforaphane.
- Which is, really, for people listening,
that's so important because
a number of compounds
that people take in supplement form
don't cross the blood-brain barrier,
or they get metabolized in ways
that what's listed on the
bottle almost becomes irrelevant
for what your cells actually experience.
So that's very reassuring.
We will get back to heat and cold
and this theme that I tried to surface,
but I just find this too interesting
to diverge at this
point from these themes.
So, what other compounds or micronutrients
do you place in the top
tier of useful, interesting?
There are animal studies.
Maybe there are hopefully
also some human studies.
We've talked about a few.
I know you've talked a lot
about omega-3 fatty acids.
So, if you had to do your top three,
your superstars of nutrients
for the brain and body,
sounds like we've got one set,
what would you put alongside them?
- Omega-3, the marine omega-3 fatty acids.
So these are found in
marine types of animals,
fish, cold water fish, fatty fish.
So there's three fatty acids.
There's one from a plant,
and that's often referred to
as ALA, people call it short,
alpha-linolenic acid,
and then there's
eicosapentaenoic acid, or EPA,
and docosahexaenoic acid, which is DHA.
Yeah, but EPA-
- I'm amazed you can pronounce
two of the most difficult
words to pronounce and spell
right next to ophthalmology,
which, if you can spell it.
I know people who have appointments
in ophthalmology departments
that don't know how to
spell ophthalmology.
Little secret. There's
an extra P in there.
So the ALA.
I'm not going to attempt to pronounce it
because your pronunciation was perfect
of both of these two compounds.
And you said are marine sources, so fish,
so sardines, cod, this sort of
thing, but what about krill?
I've seen krill oil.
A few years back, people were saying krill
is a better source for
omega-3s than is fish oil.
I took some krill oil capsules,
made me itch all over, so I stopped.
- Do you have a shellfish allergy?
- No, I don't think so.
- No, okay.
- I don't think so.
I'm not a big fan of shellfish,
but I'll have oysters every now and again,
or shrimp or something, and feel fine.
- Yeah, we can talk about sources.
So krill is a source
mostly of a type of DHA and EPA
that's in phospholipid form.
So it's a phosphatidylcholine
omega-3 fatty acid,
and that's different than most of the,
well, if we're talking
about fish oil supplements,
that's a different story,
but if you're talking about comparing fish
to eating krill, like we're
talking about the food.
- Oh, I would never eat krill.
- Okay. Are we talking
about the supplements?
- Yes, I apologize.
- Fish oil supplements.
- Yeah, krill supplement
versus fish oil supplement,
and, if it fits in the conversation,
talking about great sources of
omega-3s in their whole form.
I have a bad feeling you're
going to tell me sardines.
- Sardines are, yeah,
they're awesome. Anyways.
- Except for the taste.
- And for the potential contaminants.
Mercury, I think, was one.
No. Yeah, it was mercury.
And Joe was telling me about,
he used to eat sardines everyday.
Joe Rogan was telling me
that he used to eat sardines every day,
and then he had really
high mercury levels.
And I was really shocked
because sardines are low
in the fish groups.
The higher up you get,
like swordfish and sharks,
like, really high mercury
'cause they're eating all
the other fish, right?
But I think some brands,
and if you look at ConsumerLab.
ConsumerLab, it's like a third-party site
that I'm not affiliated with,
but I'll use them because
they do a lot of analysis
of different foods and supplements.
And so you can look at
some of their sardines,
and they have a list of
ones that are pretty decent.
But, anyways, back to your question
about fish oil supplements
versus krill oil supplements.
So one of the major differences
is that fish oil supplements,
if you get a high quality one,
it's in a triglyceride form.
So you've got a glycerol backbone
with three fatty acids that's attached,
and those are either DHA or the EPA.
Or, if you have a lower
quality fish oil supplement,
then you have what's
called ethyl ester form.
And, typically, the reason for that,
when fish oil is purified,
it's run through this column
with alcohol or something.
They cleave it off, the glycerol backbone,
and then it's just kind of
easier to leave it like that
than re-esterifying it,
which costs more money.
So you can get it in ethyl ester form,
which isn't as bioavailable.
And, in fact, if you
don't take it with food,
you're going to be in trouble.
You're not going to
absorb much of it at all.
- Would you see this on the packaging?
Is it going to say it's
in this ethyl form?
- Some official brands will
put it on their website,
perhaps on their packaging,
but, most of the time,
you'll have to dig for it
on the website and/or call them.
But I think, for the most part,
ones that are higher end will market it,
like triglyceride form.
And it's not that ethyl ester's bad.
It just means take it with food.
So one of the major prescription
omega-3s out there is,
both of them actually, Lovaza,
which is a mixture of DHA and EPA,
as well as Vascepa, which
is a highly purified EPA.
These are both prescribed by physicians
to patients with hypertriglyceridemia,
so high triglycerides among other things,
I think maybe dysregulation
of lipids as well.
- This is amazing.
For people, so these
are prescription drugs
that are essentially very
high-potency, purified omega-3s,
but they're given to
people for lipid issues.
So this is the treatment of
issues with fat metabolism
by giving people fat.
- Yes.
- I just want to push home,
again, I'm not carnivore keto
or anything, I'm an omnivore,
but to just push home that
one thing that's so wonderful
that you've done over the
years and you continue to do
is to move away from these
very broad, sweeping statements
about fat is bad.
Here's a case where we're
saying fat is not only good,
it can be used to combat
issues with fat metabolism.
And fats are not just one
thing. They're many things.
So anyway, I just want to
put a little highlighter
and a point of appreciation there
and make sure that people are
sensitized to the fact that,
if you hear that fat is bad,
you have to ask, what kind of fat?
And here we're talking
about these omega-3s.
Okay, so the triglyceride form
can be taken with or without food,
and there's prescription forms.
I don't know if I can get ahold
of the prescription form unless-
- You have high triglycerides.
- Or I have a friend
with high triglycerides.
No. It's illegal, folks.
Don't share prescription drugs.
- Or you talk to your doctor and you say,
"I'm already taking this from..."
I mean, I don't know
how it works. Anyways.
- What's the dosage that
you recommend people get?
One way or another.
- All right, okay, so the
dosage that physicians prescribe
for high triglycerides, for
example, is four grams a day.
- Four grams of EPA.
- Yes, of the Vascepa.
I think Lovaza's also
prescribed at four grams a day.
And you can get either of
those from your physician.
My father-in-law just got
one of 'em prescribed.
We were buying our own
omega-3 for years and years.
It's like, hey, you can actually get this
and health insurance can cover it.
And it's a really purified form,
but you have to take it with
food. That was the bottom line.
I've totally gone on tangents,
but you're asking more
interesting questions anyway.
- Well, normally I ask about mechanism
and then I talk about
protocols, but in the-
- Or the why.
- [Andrew] Or the why.
- I mean, we haven't gotten there yet.
- And we definitely will get there,
but I think a number of people nowadays
are just really excited
about what they can do
for their health, and so, here,
we're just raising the
importance of omega-3s,
and then we'll definitely get to the why
and the underlying mechanism.
- Yeah, I think four grams is,
I mean, in fact,
Bill Harris, Dr. Bill Harris,
he's just one of the pioneers
on omega-3 fatty acid research.
He was on our podcast last August.
And he was saying the reason
FDA chose that was literally
just because how much they
could get people to take.
It wasn't like an upper end,
like anything above that is unsafe.
That wasn't the case.
I mean, it was just purely cost
and compliance,
so what they can get into a
pill, the amount they can get,
and how many pills they
can get people to take.
- I'm smiling because our
good friend Satchin Panda
at the Salk Institute,
who's done a lot of important
work on intermittent fasting
and other incredible work on
circadian rhythms, et cetera.
When I was talking to him
in preparation for an episode
on intermittent fasting,
I said, "Why the
eight-hour feeding window?"
And he said, "Well, the graduate student
"who ran those studies had a partner."
I think it was a girlfriend, as I recall.
Hope I didn't get that backward.
And the partner said,
"Listen, you can be in lab
"10 hours a day, but you
can't be in lab 14 hours a day
"if you want this relationship to work."
And so it was eight
hours of feeding window,
plus some measurements and
time to walk into the lab,
park the car, et cetera.
And so the eight-hour feeding window
that everyone holds so holy
was actually just born
out of this relationship
between these two graduate students.
Had they been single,
I was single all through graduate school,
or most of it anyway,
and I lived in the lab.
So, if it'd been me, intermittent fasting
would mean eating 14 hours a day.
That was a joke.
Not a good one, but just want
to make clear. I'm joking.
But the point that you're
making is a really good one,
that the four gram amount
is not a threshold based on anything
except the threshold
of people's willingness
to actually take this stuff.
And I think that's important
for people to hear.
Because so often we hear the
eight-hour feeding window,
four grams of EPA, 150 minutes of cardio,
and it's really a question
of what you can reasonably do
in a study.
- So I take four grams a day.
I take two in the morning,
two grams in the morning,
and I take two grams in the evening.
I take my EPA in the morning,
and I take my DHA in the evening.
- You split them.
- I do.
I don't know.
I don't think it's necessary, necessarily.
I just happen to get a
certain fish oil supplement
that separates them.
And so, like Lovaza, Lovaza's a great one,
and it's all in one, and it's easier.
- What if someone doesn't
have a prescription?
So I take over-the-counter fish oil.
I know I feel better
'cause I've done the
experiment of going on and off.
I take them mainly for,
I don't have depression,
but my mood is better.
My joints feel better. I just feel better.
And I like to think that my
platelets are slipperier,
and they're cruising through
any little obstructions
in my veins or arteries.
That's the image I have in my head,
but I don't have any data
to support that part.
- Yeah, I mean, so, if
you're asking for, like,
where do people get these
fish oil supplements?
- Let's say I look at the bottle,
and it says two grams per serving,
but then I look, and it's
750 milligrams of EPA
or 1,000 milligrams of EPA.
Let's say half of it is EPA.
Then, do I want to hit a threshold of EPA
or a threshold of what's
listed on the bottle,
on the front of the bottle?
Because my understanding
is that we need to hit
a threshold level of EPA
in order to derive these
important benefits.
- I think two grams is a good threshold.
Now, the International
Fish Oil Standards, IFSO,
they have a website where
they do third-party testing
of a ton of different fish oil supplements
from around the world, and
they measure the concentration
of the omega-3 fatty acids
in the actual supplement,
because nothing is ever
what it says on the bottle,
and then they also measure contaminants,
so mercury, PCBs, dioxins,
things that you'd find potentially in fish
that are harmful to humans,
and they also measure mercury
and then oxidized fatty acids.
So these omega-3 fatty acids
are polyunsaturated fatty acids,
which are extremely prone to oxidation.
So please keep your fish
oil in the refrigerator
because it's colder.
Yeah, they're extremely prone.
- Mine's in the cupboard,
so now I know.
- The shelf life's
increased. Lower oxidation.
- No, it makes perfect sense. Yeah.
- So, anyways, they measure that.
And I typically like to look for,
they give you a total oxidation number.
It's called T-O-T-O-X.
TOTOX is what we call it for short.
And I like it to be at the least under 10,
ideally under six.
It's really hard to find all
the right mixtures of things,
but people can go to this website,
and they can browse through the products.
I've put together an Excel sheet,
which I have a YouTube little screencast
that I'm yet to publish,
press the publish button on,
but it, basically,
you have to go back and check and update
'cause these are from different
lot numbers of the products.
They do have up to like
20, 27 or something.
And so I've gone through
and found my top picks
of high EPA brands and high DHA brands.
If I were to buy some, the
ones that I would choose
because of the low total oxidation
and the high concentration
of either EPA or DHA.
Now, people can go and do this themselves.
It just takes some work.
- No, I'm glad that you did the work.
I'm going to put up a tweet every week.
- Oh no!
- With you tagged until this
list is published online.
Sorry, Rhonda, but I'm going to do it.
I know it's very sadistic of me,
but in service to the community
and myself.
- Yes,
and I chose five brands from each,
and I tried to find one in Europe
and one in Canada.
- Great.
- So there's a great selection
of US and other.
- Thank you
for doing that work.
I don't want to do that
work, and I trust you.
So, yeah, I try and get
two grams per day of EPA
from supplementation.
I'll now put it in the refrigerator.
Mood is better.
I made that decision
mainly based on the data
that I'm aware of,
looking at comparison of people doing that
anywhere from two to
four grams of EPA per day
compared to SSRIs, selective
serotonin reuptake inhibitors,
in treatment of depression,
and I don't want to take
an SSRI if I don't have to,
and fortunately, I don't have to,
but the data, by my read, are remarkable.
People that take these
things in sufficient doses,
meaning the EPAs,
are able to get by with much lower dosages
of SSRIs for depression relief
or, in some cases, to come
off their SSRIs completely
or avoid going on
antidepressant medication.
Now, of course, this is not
something people should cowboy.
Mental health issues are serious.
But what other reasons,
I'd love your thoughts on that,
on the mental health part,
so maybe you could tell
us what are some things
that getting to two to
four grams of EPA per day
is going to help with in our
brain and the rest of our body.
- So, do you know?
So I actually published
a paper back in 2015
about the role of omega-3
and vitamin D in depression,
bipolar disorder, schizophrenia,
and impulsive behavior.
But, so, within that paper,
doing background research,
and this was a review article, by the way,
I was just connecting dots
'cause I love doing that.
- I'm going to grab that paper.
I confess, I don't know the paper,
but I love quality reviews
because the references
they're in are so useful.
- Well, there's a huge
role for inflammation,
the cause of inflammation in depression.
And I think we did a short
animated video on this as well,
years ago, back when I
was publishing that work,
where people are injected
with lipopolysaccharide.
This is something that we're
generating from our gut,
mostly from our gut permeability,
which happens a lot.
Endotoxin, it's also called.
It's endotoxin lipopolysaccharide.
It's basically the outer
membrane of bacterial cells
when bacteria die, so like when
the immune cells in our gut
come into contact with the bacteria
because we drank alcohol five
days in a row or whatever,
we release endotoxin, or
something stressed us out.
We release endotoxin into our body,
and that causes inflammation.
And so you can inject people
with lipopolysaccharide
and cause depressive symptoms.
However, if you take those
same cohort of people,
give them EPA,
and I think it was
somewhere around two grams,
and then inject them
with lipopolysaccharide.
We're establishing causation here, right?
It totally, the depressive
symptoms, versus a placebo.
So the placebo was saline control.
So this was a placebo controlled
because obviously it's hugely
important for depression.
It ameliorated the depressive symptoms
that was caused by lipopolysaccharide.
- Amazing, and LPS,
lipopolysaccharide, is no joke.
Years ago, when I was working
on thermal regulation,
we would inject animals
with LPS to induce fever.
The vagus nerve registers
the presence of LPS signals
to these particular hyperglycemic areas
and cranks up body temperature
because, basically, it's a
signal that the body is infected.
Amazing.
So I will continue with
my two grams per day.
Maybe I'll ramp it up to four.
I'm not doing the DHA separately.
There's DHA
in the same supplement.
- Yes.
- [Andrew] Is that okay?
- Yes. Yeah, yeah.
And to kind of...
Boy, we've got a lot of
things to hit back on
because one of your original questions
was krill oil versus fish oil.
- Yes, still in the cue.
- DHA, specifically,
in phospholipid form,
it's more bioavailable.
So, if you're comparing exact
quantity or concentration
in triglyceride form
versus phospholipid form,
you will get more in your plasma cells,
in your plasma, plasma cell,
in your plasma with krill oil.
However, krill oil
supplements are so low dose.
I mean, good luck getting two grams
of omega-3 from krill oil.
And also, krill oil supplements
are notoriously rancid.
I don't know for whatever reason.
- Maybe that's what
made me itchy all over.
- I think they're just...
I haven't found a good
krill oil supplement.
I pretty much stay away from it.
I mean, if you smell it too,
I mean, it just smells rancid.
So, but the thing is,
and I also published a
paper on this back in 2019,
yeah, something like that,
about DHA in phospholipid
form getting into the brain
through a different mechanism
than DHA in triglyceride form.
And so it's going through a transporter
called the MFSD2A transporter.
And I think it's very relevant for people
with an APOE4 allele, so-
- People with an
Alzheimer's susceptibility.
- Right, so like 25% of the
population has an allele
and a gene called APOE4,
and, basically, it's APOE,
but the four is referred to
as the bad kind of version of it.
This is something in our
bodies. It's also in our brain.
And if people have one of these versions,
if they got one from
their mom or their dad,
they have a twofold increased
risk for Alzheimer's disease.
If they get two, which is much more,
it's less common.
I think it's like 2% of
the population or something
has two alleles, but they have like a 10
or 11-fold increased risk
of Alzheimer's disease.
So there is a role for
phospholipid form DHA in the brain,
but you also make phospholipid
DHA inside your body.
And you can do that by taking
in more triglyceride forms.
So two grams or more is
the magic number, I think.
So kind of back to the why for fish oil.
I personally think it is
one of the most powerful,
anti-inflammatory things,
dietary lifestyle,
things that we can get
easily, relatively easily,
that is going to powerfully
modulate the way you think,
the way you feel, and the way you age.
And a variety of
different types of studies
kind of led me to that conclusion,
a variety of observational studies.
So there's been lots of
work by Dr. Bill Harris
and his collaborators looking at,
it's called the Omega-3 Index.
So this is actually the omega-3
level in red blood cells.
So red blood cells turn
over about every 120 days.
So it's a long-term
marker of omega-3 status.
This is very different from
99.9% of any study you see
or any lab that you go to to
get your omega-3 levels tested.
You're getting your plasma
phospholipid levels tested,
which is kind of like
you can think of it as,
what did I eat a couple days before?
Oh, I had fish. My
omega-3 levels are great.
But did you eat fish like that every week,
or was it like you went out to dinner?
So it's not a great biomarker
for long-term omega-3 status.
It's kind of like the
fasting blood glucose levels
versus the HbA1c, which
is like a long-term marker
of your blood glucose levels.
So the Omega-3 Index.
He's done a variety of
studies, observational studies.
So, for people listening,
these are studies that
are obviously flawed
because they're not
establishing causality.
You're looking at people's lifestyles.
But, in the case of Bill Harris's work,
he's measuring something.
So he's measuring the Omega-3 Index.
And he's measuring the
Omega-3 Index in people,
and then looking at their
mortality risk, for example,
or their cardiovascular disease risk.
And what he has found is that,
first of all, standard American diet
has an Omega-3 Index of 5%.
Japan, by contrast, has an Omega-3 Index
of around 10 to 11%.
Big difference there.
And they also have about a five-year
increased life expectancy
compared to people in the US.
- Do you think that's mainly
due to their fish intake,
seafood intake?
- So what he showed was,
I think it's a big part of it.
I mean, you can't says
it's the only thing,
but what he showed in his data was that,
and I think it was Framingham Study,
where he looked at the Omega-3 Index,
and people that had a
Omega-3 Index of 4% or lower,
so close to what the standard American is
but a little bit lower,
they had a five-year
decreased life expectancy
compared to people that
had an 8% Omega-3 Index.
And so big difference there, right?
Five years life expectancy.
But here's the really
interesting thing, Andrew.
He also looked at smokers,
smokers and their omega-3 levels,
and so he stratified
it, and he found smokers
that had no omega-3 were
like the worst of all.
I mean, it was just like worse, right?
We all know smoking is bad for us
and will take years off
our life expectancy.
- [Andrew] Absolutely.
- But smokers that had the high level,
like smokers that were taking
their fish oil or eating fish
or whatever it was they were
doing to get them up to 8%,
they had the same life
expectancy as non-smokers
with the low Omega-3 Index.
- [Andrew] Wow.
- Right?
- Wow.
That's amazing.
And it's also amazing to me
that people still smoke cigarettes.
But I see a lot of people vaping,
and I know a lot of
people consume cannabis.
Have there been any studies
specifically of vaping
or people smoking marijuana?
- Life expectancy?
- All-cause mortality.
- I haven't seen those.
I haven't seen those.
- They're not motivated enough to come in
as research subjects.
That was, again, a poor joke.
It is hard to study people, marijuana use,
unless, I'm told by my
colleagues that study this stuff,
unless you offer people marijuana,
in which case they'll do it.
But, again, they're actually
not very good research subjects
in all seriousness 'cause
they are not very motivated
or consistent, and they
forget their appointments.
So that's incredible.
And you mentioned that
the data on pollution
related to the plant compounds earlier.
So it's almost like these things are,
again, are acting in a reparative way.
- The omega-3s are, I mean,
they are resolving inflammation.
They're blunting inflammation.
They're doing so many different.
They affect so many different parts
of the inflammatory pathway,
which is, I think, plays a
huge role in the way we age,
the way our brain ages, the way we feel,
our mood, our joints, all that.
And so it's amazing
that it's not, you know.
- I love fish oil. I feel
better when I take it.
I try to eat some fatty
fish a couple times a week.
I do want to just touch on
food sources for a moment.
First of all, are there plants
that are rich in omega-3s?
And second, I have some friends
who are really into meat.
I like meat a lot, my dad's Argentine,
but I don't eat very much of it.
I try and eat high quality meats
in relatively limited amounts,
but I do eat pretty often.
But I've been told by these sources
of a questionable authority that,
if an animal grazes on really
good grasses, for instance,
that the meat can contain
a lot of omega-3s,
which, in principle, makes sense
based on this Omega-3 Index.
'Cause you're telling me
that a lot of this omega-3
is sequestered into the red blood cells.
So, if I'm eating high
quality, grass-fed meat
and the grasses had omega-3s,
do my steaks have omega-3s or no?
- So there was a study published
that compared conventional meat,
so meat that animals are fed
corn or soy or whatever it is.
- Which is terrible.
- [Rhonda] Yeah.
- For animals and people,
as far as I can tell.
I'm sure I'll get some
attacks, but that's okay.
I won't read those comments.
Again, a joke. I read all the comments.
But it seems to me that these animals
have to either be taking fish oil
or eat plants that are
very rich in omega-3s
in order for the meat
to actually contain sufficient omega-3s.
- So the meat, comparing
the conventional meat
to the grass-fed or
pasture-raised cows or cattle,
there were higher levels
of alpha-linolenic acid.
And ALA, it can be
converted into EPA and DHA,
but the conversion is very inefficient
and very dependent on
a variety of factors,
including genetics.
Genetics, a huge regulator.
Some people can do it much better.
Others, you're getting like
5% of conversion to EPA.
Estrogen is a major regulator
of making that more efficient.
It makes sense because pregnancy,
when your estrogen just
goes through the roof.
These omega-3 fatty acids
play a very important role
in brain development.
Women are supposed to be
converting any ALA they can
into the longer-chain omega-3 fatty acids.
So estrogen does affect that,
but I would say plant sources.
So, if you're looking for the ALA,
plant sources would be walnuts, flaxseeds.
Those are probably the highest.
But, if a person is a
vegan or a vegetarian,
their best bet is to
actually get microalgae oil.
And you can supplement with microalgae oil
because microalgae, they do make the DHA.
And so that would be a better source
for people that are vegetarian and vegan
rather than doing the flaxseed oil
because that conversion inefficiency,
the enzymes that convert
ALA into EPA and DHA,
again, it's inefficient.
- And then, for people that eat fish,
sardines, you said.
- [Rhonda] Salmon.
- Salmon, and you have to eat
the skin, as I understand.
- You don't have to, but it's good.
- [Andrew] It's rich with omegas.
- The oil, yeah.
And the reason I say,
I think the best would
be wild Alaskan salmon
versus the farm-raised because
the farm-raised, again,
they're feeding 'em corn.
They're feeding 'em grain and stuff.
- [Andrew] Really?
- And then, they give 'em astaxanthin.
So astaxanthin is a carotenoid.
It's the carotenoid that's
in things like krill,
crustaceans that make their red pigment.
- Yeah, it's also being
used now as a supplement,
and there's a prescription form
to try and rescue some
age-related vision loss
because of the role of
the vitamin A pathway
and photoreceptors.
- Yeah, well, actually the
carotinoids themselves,
so like lutein, zeaxathin,
they're really good at
sequestering singlet oxygen,
which is damaging, right?
- Yeah, as we age,
because the retinal cells,
the cells of the eye
are so metabolically active,
they accumulate a lot of
reactive oxygen species,
and mitochondrial repair
and limiting reactive oxygen species
is a major theme of
trying to rescue vision.
That's a whole other podcast and story.
There's some really interesting data now
on the use of red light to try and trigger
these pathways.
- I've seen some.
That's my good friend of many
years and amazing scientist
Glen Jeffery's lab at
University College London.
We should talk about that
at some point, if not today.
- I saw that study, like 2020, was it?
- Now, they have a second study.
- Oh, do they? They've done, okay.
- It's looking real.
- [Rhonda] That's exciting.
- I mean, they're cautious.
They're appropriately British
and cautious about it.
I always joke if those studies
had been done over here,
everyone would already know about it.
Glen is a very conservative guy,
but they've done this stuff
now in pigs, in rodent models,
and now also two studies in humans.
It's looking pretty interesting.
So sardines but also anchovies.
By the way, I hate all the
food items that I'm describing.
I can barely tolerate salmon.
I don't like fish at all.
Actually, I like live fish.
- So fish oil's good for you.
- I had fish tanks when I was a kid.
No, I find fish, unless
it's in sushi form,
I find it absolutely repulsive,
and I don't know why.
I probably have some mutation.
- So raw fish is actually
higher in mercury than cooked.
- Okay, well, that's good.
I don't really like
sushi that much anyway.
You're giving me great
reasons to not eat fish,
except I should eat
these other fish sources
or supplement more heavily.
That's the message I'm getting.
- I eat sardines.
Every day, my first meal almost
is a can of sardines and an avocado.
- Avocado is good.
- I love it, yeah, with
a little bit of lemon
and then some little hot sauce.
- Does avocado have omega-3s?
- Avocado is very good
in monounsaturated fat.
It's not really high
in polyunsaturated fat.
Omega-3, really, it's
either the DHA and EPA
that's in the marine sources fish,
or it's the plant ALA source,
which is the flaxseed or the walnuts.
- It's rough.
I mean, all these companies now
are making these plant-based
products that taste like meat.
My wish is that they
would just make a fish
that tastes like a steak, but that's-
- The fish come out albino,
the ones that they farm raise,
because they don't eat any of the-
- I'm joking.
I don't want a genetically modified fish
that tastes like a steak.
Although, I love the taste of steak.
The point here is that, if
one doesn't see themselves
regularly consuming these
fish sources of omega-3s,
it seems to me that the
only way to really get them
is from supplementation.
- And supplementation is a
good way to get a high dose.
And to get back to your dose point,
there was a couple of
studies that, basically,
I think there was some way
they showed that people
that are in the 4% Omega-3 Index range,
in order to get to the 8%,
the five-year increased life expectancy
if we're comparing the two groups,
was to supplement with at least two grams.
It was about two grams a day.
And I think it was a little bit less
if it was triglyceride form,
but I think two grams
is a good, safe number.
So most Americans that are
not eating a lot of fish
and they're not supplementing
are probably around a
4 to 5% Omega-3 Index.
And to get to the 8%.
And I think that's a good empirical way
of thinking about it, right?
Okay, well, I want to get to that 8%.
By the way, I'm almost 16% Omega-3 Index.
- Yeah, I was going to ask about testing.
So, where and how can somebody
measure their Omega-3 Index?
Which, again, just to remind people,
is essentially the percentage of omega-3s
that you have in your blood
with the caveat that the Omega-3 Index
will be heavily biased by what
you ate in the previous days.
- Not the Omega-3 Index.
Okay, so, the Omega-3-
- Sorry, I misunderstood.
I thought you said, in red blood cells,
if I ate salmon two days ago,
my Omega-3 Index is going to go up.
- No, that was plasma.
- [Andrew] I misunderstood.
- So most people are measuring,
if you look at a lot of
studies, and honestly, Andrew,
I think a lot of the
reason for conflicting data
is because people are measuring
plasma omega-3 levels.
- [Andrew] Okay.
- The phospholipids. It's
in a phospholipid, right?
Your phospholipids are carrying things.
These are lipoproteins.
They're carrying things like omega-3
and triglycerides and stuff
and shuttling 'em around.
The Omega-3 Index is actually
in the red blood cells,
and red blood cells take
120 days to turn over.
So, if you're going to do a baseline test,
if you want to know before
supplementing what your level is,
you have to wait 120 days
before doing the second test
after supplementing to
know how much you went up
because that's how long it takes
for your red blood cell to turn over.
So the Omega-3 Index.
Bill Harris has a company
that he co-founded.
It's called OmegaQuant,
and they measure the Omega-3 Index.
They have a variety of
different index tests.
You can do a basic one or
a little more advanced.
- This is from a blood draw.
- It's a little blood spot thing, yeah.
And he uses money to funnel
back into doing lipid research.
He's out there doing all
sorts of interesting studies
on omega-3s, so it's great.
But the Omega-3 Index is great.
I think that, honestly, more people
and more researchers should be using it
because the conflicting data,
it always comes down to
what we're measuring,
the sensitivity of it.
Are we even measuring anything?
So you're giving someone
500 milligrams of DHA,
and you don't see any effect.
Well, did you measure
what their levels were?
And did you measure the Omega-3 Index?
There's all sorts of problems
with randomized controlled trials,
and I think that we
need to, as scientists,
we need to come together
and make some progress.
I mean, you know? Let's
all talk to each other.
Let's figure things out.
This test is out there. It should be used.
It should be used not just by
Bill's group, but everyone.
- Yeah, well, and I'm
learning so much from you.
And I agree we need more collaboration.
I've always enjoyed really
fruitful collaborations
in my lab at Stanford.
Collaborating is just so much more fun.
Online, there seems to be a
bias more towards creating silos
as opposed to bridges,
but I appreciate that
you bring up the need
for more collaboration.
And knowing which measures are best,
and, in this case, now, thank
you for the clarification,
I understand this Omega-3
Index is going to be best.
So, basically, now, when I look at you,
I think, you are 16% omega-3.
- And dolphins are 19%. I'm almost-
- Is that your goal?
You're trying to get there.
- It is. [laughs]
- Interesting.
Actually, they should
probably do something
where you're trying to
achieve the omega-3 ratio
of your favorite species.
Now that we've covered a bit
of how to get these things
into one system, depending
on what one eats, et cetera,
and some of the better measurements,
how is omega-3 and some of
these other related lipids,
how are they having
these positive effects?
In my mind, and this is
incredibly elementary,
but my understanding
is that, at some level,
they're making platelets more slippery.
Is that true or not?
I'm happy to be wrong.
How is it possibly impacting my mood?
Is it through the synthesis
of membrane on neurons
that allows neurons to
release more transmitter,
like serotonin and dopamine?
What are some of the purported, reported,
and known mechanisms?
- I think some of the
most well-known mechanisms
do have to do with the omega-3 fatty acids
being very powerful regulators
of the inflammatory process
in some way, shape, or form,
whether that has to do with
resolvins that are produced
from the metabolites of DHA, for example.
Resolvins play a role in
resolving inflammation.
You want your inflammatory
response to be activated
when it's supposed to be,
but you want to resolve that inflammation
and the inflammatory response
in a timely manner, right?
And resolvins help do that.
And so resolvins are one,
and then there's these specialized
pro-mediating molecules,
the SPMs, that also help
resolve the inflammation.
There's, like you mentioned,
the leukotrienes and prostaglandins,
and these things are
being affected by EPA,
and they do affect platelets
and platelet aggregation,
and they do affect that
whole pathway as well.
I think there's just so many
different ways and inputs.
And so, when we talk about inflammation,
honestly, that's a big general term,
but when you're talking
about serotonin release
at the level of neurons,
we know that these inflammatory molecules
cross the blood-brain barrier.
I just mentioned ago
about injecting people
with lipopolysaccharide and
causing and depressive symptoms.
It's known that omega-3,
actually specifically EPA,
is able to help serotonin.
Inflammation inhibits
the release of serotonin,
and so EPA is actually able to
blunt inflammatory responses
along with DHA as well.
DHA does that through resolvins and stuff.
And this then helps more
serotonin be released
because you're not having
so much inflammation
getting into the brain
and affecting serotonin release, right?
That's one mechanism.
And then, another would be,
well, DHA itself has been shown,
it's a very important fatty acid
that makes up cell membranes,
many cell membranes,
including in our neurons.
And, as you very well know, Andrew,
the structure and function
of receptors of transporters,
these membrane-bound proteins
on the surface of our cells,
including neurons,
are affected by the membrane fluidity,
like how rigid and how
fluid the cell membrane is,
and DHA plays a role in that.
And so, for example, in animal studies,
if you make an animal deficient in DHA,
their serotonin receptors,
dopamine receptors,
they're affected because the
structure of them is affected
through the fluidity of the membrane.
And so I think that's another mechanism.
And I'm talking sort of general
'cause I'm not a neuroscientist.
- No, but it makes perfect sense.
We know, for instance,
neuroplasticity almost always
involves the recruitment of more receptors
or an improvement in some feature
of receptors to neurotransmitters.
And they literally move
laterally in the membrane.
They kind of float
around like little rafts.
Sometimes they are, in
fact, in lipid rafts.
So it makes perfect sense
that these molecules like DHA,
which are part of the
structural fat of the neuron,
because, of course,
the outsides of neurons
are basically fat,
not just the myelin that
people have heard of,
but the actual membranes,
that getting that right,
you wouldn't want it as rigid as concrete,
but you wouldn't want it as soft as...
Need to come up with something here.
What's that gooey stuff
that kids play with?
It's like that goo. Anyway.
- Oh, yeah.
- Yeah, it's disgusting,
and it's too soft to be
a membrane for a neuron.
- You get it in those machines,
like the claw machines.
- Someone put it in the comments
and tell me what that
disgusting gooey stuff is.
You don't want your
neurons to be that gooey,
and yet you don't want them
to be like concrete either.
- It's a balance. Yeah.
- It's a balance.
And, in mentioning DHA, I
realize I'm backtracking,
but I want to make sure that we close
all the hatches for people.
We talked a lot about EPA,
but are food sources of DHA
that you find particularly attractive,
either by taste or by potency for DHA,
what are just a few
that we could throw out?
Because I am aware that
there are supplements
where you can get a nice
ratio of EPA to DHA,
or you take them separately, as you do.
But if I want to make sure
that I'm getting enough DHA,
what do I need to be sure I'm
eating on a regular basis?
- Well, the fish is packaging
the DHA and EPA in the ratio,
but I also do eat salmon
roe, which is very salty,
and it's a really high source
of the phosphatidylcholine DHA
that we talked about.
- So this is fish eggs.
- It is, and actually-
- [Andrew] That I like for some reason.
- Oh, do you?
- Yeah, so I'm discovering
something about myself.
This was not meant to be
nutritional psychotherapy,
but you're doing that for me anyway.
I'm discovering that, yeah,
I like eating embryonic fish.
I just don't like eating the actual fish.
- Okay, well.
- Okay, so fish eggs are
okay. So caviar, basically.
- Caviar, yes.
And that's a good source
of the phospholipid form.
And I was consuming that a lot
because I wanted to get
the phospholipid form.
- [Andrew] Yum!
- And it's actually really good.
There's been some animal studies
in piglets and rodents as well
showing that consuming phospholipid DHA
during fetal brain development
gets like 10 times more DHA in the brain.
Again, it's-
- Makes sense based on fetal development.
So, do I need to buy beluga caviar?
Stuff can get pretty expensive
at $200 a tin.
- I don't think you need to.
I think it's a matter of preference.
And if you're supplementing
with your two to four grams of fish oil,
I mean, you're going to get
phospholipid form anyway
'cause your body's going to make it.
- Okay, I've seen some containers
of what I assume to be quality fish eggs
that are not at the caviar level
that you can find in the
better grocery stores
that aren't super expensive.
- [Rhonda] Right.
- I wouldn't dip as low as to go eat,
for instance, like fishing bait.
Like, when we were kids,
we used to go fishing,
and you'd put the fish egg on the thing.
That's probably not good.
- No.
- Although it's good enough
for the fish apparently. Okay.
Only half joking here, folks.
I'm just trying to protect
you from yourselves.
Don't get any crazy ideas
about eating fishing bait.
Okay, so that's great to know.
So we have these plant-based compounds,
we have the omega-3s, so EPA, DHA,
and then you mentioned
there's a third category.
What would you place
in your third category
of foods or supplement-based nutrients
that our health, brain and/or body health,
can really benefit from?
- I mean, I think the most
obvious would be vitamin D,
which is actually, as you
know, a steroid hormone
that we produce when we're in the sun.
Depending on the time of year,
we can make it in our skin.
And depending on how much
melanin we have on our skin,
or whether or not we're wearing
sunscreen or how old we are,
there's a sliding scale on
how efficient that process is.
- As I understand, there's
an inverse relationship,
where the darker your skin is naturally,
the more vitamin D you need to consume.
Is that right?
- Well, the darker your
skin is, the harder it is.
So there was a study out of
the University of Chicago,
this was several years ago,
where they looked at African Americans
and compared African
Americans to Caucasians
with light skin, fair skin,
and how well they could make
vitamin D from sun exposure,
and how long they had to be
in the sun to make X amount.
And it turns out that African Americans
with darker pigmentation,
which protects them from
the burning rays of the sun,
it's a natural sunscreen,
had to stay in the sun six times as long
as someone with none of
that natural sunscreen.
So I think the take-home
there is a lot of people
with darker skin living
in Sub-Saharan Africa,
or people living in
India with darker skin,
or in the Philippines,
you know, these equatorial regions
where you tend to see darker skin
because it's protection from
the burning rays of the sun.
- An adaptation.
- They are in the sun more,
and they're getting more vitamin D,
but people that maybe
moved to United States,
to like Minnesota, or in a
place where UVB radiation
isn't getting to the atmosphere
12 months out of the year.
It's only getting there
four months, for example.
Or even living in our modern day society,
where people just don't
go outside anymore.
I mean, we're inside.
We're at our laptops in school.
We're at work. We're in
our cubicle, whatever.
So supplementation does play a major role,
not only for people with darker skin
that aren't outside all
the time, but for everyone.
70% of the US population has
inadequate vitamin D levels.
70 of the whole US.
- [Andrew] Amazing.
- So this is everyone.
And so I think that insufficient levels
defined as less than 30
nanograms per milliliter,
and that's defined by
the Endocrine Society,
looking at a lot of
different aggregate studies,
all-cause mortality, for example.
There's been a lot of
different meta analyses
of all-cause mortality studies,
where vitamin D levels
really seem to be ideal
between 40 to 60 nanograms per milliliter.
And so, in order to get to that level,
if you are not outside all the time,
live in Southern California,
where you're always outside
without sunscreen on.
I always wear sunscreen
because I'm trying to protect my skin
from so many wrinkles and stuff,
but also skin cancer is
somewhat of an issue as well.
So, basically, the point is that vitamin D
is a steroid hormone,
meaning it actually binds
to a receptor and another
receptor dimerizes with it,
the retinoid receptor,
and that complex goes into
the nucleus of a cell,
where your DNA is,
and it recognizes little sequences of DNA
called vitamin D response elements.
They're called VDREs.
They're specific sequences
of DNA that this complex,
vitamin D bound with
the vitamin D receptor,
goes inside and recognizes
and turns on a whole host of genes,
turns off a whole host of genes.
I mean, this is important stuff.
Imagine 70% of the population
having insufficient testosterone, right?
It's a steroid hormone.
- We might be headed
there, but probably not.
No, I think that names are very important,
and I think that one of the
issues is that vitamin D
is called vitamin D.
It's not called DHEA or
variant blah, blah, blah.
It doesn't sound like a hormone.
I'm glad that you're mentioning
skin as the major interface
between the environment
and vitamin D synthesis
because a lot of people think of skin
as just a protective sheath around us
or something to adorn
ourselves with earrings
or tattoos or whatever,
but skin obviously serves those roles,
but the skin is an endocrine organ.
It has the capacity to make
things that impact hormones
and to make hormones.
There's this beautiful
study out this last year.
This took place over in Israel,
where they had people get outside
for 20 or 30 minutes a
day, three times a week,
exposing a culturally acceptable
yet substantial amount of
their skin during that time,
and saw big increases in
testosterone and estrogen.
And this is through a
keratinocyte-linked pathway
involving p53.
This was done in humans,
but they did some knockout
studies in parallel.
And what this study told me or reminded me
is that skin is an endocrine organ.
So the idea that sun could
trigger the activation
of production of a hormone
is really interesting
and makes total sense.
So, when vitamin D gets into cells,
and it's binding to these VDR
- [Rhonda] Es.
- Es,
what sorts of things are they triggering?
So, for testosterone,
we know it's going to
trigger protein synthesis,
muscle growth, tendon strength, et cetera,
With estrogen, it's going
to keep your neurons going,
your joints feeling good.
I always remind people that, by the way,
'cause guys always seem to want
to increase their testosterone
and reduce their estrogen.
Just remind people, if you
reduce your estrogen, guys,
your libido will plummet to near zero.
Don't crush your estrogen.
It'll also make you stupid.
If you're not already stupid,
it will make you stupid.
So estrogen's vitally important
for males and females.
When vitamin D gets into cells,
what sorts of things is it stimulating?
- Okay, so, first of all,
it's regulating more than 5%
of the protein-encoded human genome.
I say more than because, when
I was looking at this data
really in depth starting in 2012 to 2014,
it was that, and then it's now grown.
But one of the important things
that you'll find interesting
that I published on back in 2014
was that I'd gone through
this big, published database,
where someone had
published all these genes
they found VDREs in,
and basically I found that
tryptophan hydroxylase-1
and tryptophan hydroxylase-2 was on there.
And so then I started
looking at the sequence,
and I was doing some in silico work,
and it turns out that the VDREs
in tryptophan hydroxylase-2.
So, for people listening,
tryptophan hydroxylase
is an enzyme that converts
tryptophan into serotonin.
So tryptophan is an amino acid
that we get from our food.
You convert tryptophan
into serotonin in the gut,
but you also do it in the brain.
However, serotonin does not
cross the blood-brain barrier.
So tryptophan has to get into your brain,
and then you have to convert
it to serotonin in your brain.
Well, the enzyme that
does that in your brain
is called tryptophan hydroxylase-2,
and it's activated by vitamin D.
The one in the gut is actually
tryptophan hydroxylase-1.
Some of my published work hypothesized
that it might actually
be repressed by vitamin D
because it has a sequence.
The sequence itself, this
12 nucleotide sequence,
can determine, to some degree,
whether it's going to be
activated or turned off.
And I was able to kind of
look at that and think,
oh, maybe this and that.
Since then, there have been some groups
that have confirmed more with in vivo
and/or in vitro studies.
Mine was all in silico and
all that stuff, but anyways.
So serotonin, a really important one.
This is regulating our
immune cell, immune system.
It's regulating our blood pressure.
That's water retention.
Bone, of course, homeostasis.
5%. More than 5%.
I can't tell you. Like, so much.
- And with 70% of the
US population deficient,
I'm beginning to think that
this could be the linchpin
on a number of really important issues.
So supplementing vitamin
D3 is what I normally hear.
I do.
I think I end up taking 5,000 IUs,
sometimes 10 IUs of vitamin D3 per day.
Just done that for a long time,
and I've had my levels
tested and they're in range.
But I have a family member,
I'll just mention this.
I have a family member
who was not feeling well,
just kind of feeling off, a little low,
had some digestive issues,
this went on a long period of time,
was taking, on my
recommendation, 15,000 IUs of D3
and was still deficient in D3.
Now takes, and I'm not
suggesting anyone do this.
This is a special case, perhaps,
but no chronic illness
that we're aware of.
Needs to take 30,000 IUs per day
in order to bring their
D3 range just into normal,
which, to me, is striking
because they eat quite well,
they're a healthy weight, et cetera,
and it's made a tremendous difference
in terms of their mood.
Now, of course, this is correlative.
Now they feel better. They're doing it.
Who knows? They're probably
also getting outside more.
But I think people need to get tested.
They need to get their D3 levels tested.
But where and what is
a good starting range
for people to think
about D3 supplementation,
and, again, foods that can increase D3?
- So vitamin D3 is a good
way to supplement with it.
Vitamin D2 would be a plant source.
You often find it fortified in foods
like milk, usually D2.
- Does anyone still
drink milk besides kids?
- Out here, it's like
you can't find cows milk.
- [Rhonda] I mean, all the lattes
that you're getting.
- Oat milk, soy milk.
What's the other one?
- [Rhonda] They're
fortified in those as well.
- Oh, they are. Okay.
- [Rhonda] They are, yeah.
They're fortified in-
- I have a hard time
finding cows milk.
- Almond milk and oat milk
and all that stuff, yeah.
They're in all that stuff.
Vitamin D is naturally to
some degree in fatty fish.
You think about cod liver oil, right?
It has vitamin D,
but you're not going
to correct a deficiency
with eating fish for your vitamin D.
You're either going to
correct it with sun exposure,
being in the right area,
having the right amount of sun,
and being the right age,
because, as you get old,
you become very inefficient
at converting vitamin D,
making vitamin D3 in your skin.
- Well, that's probably
what was going on here
'cause this person is
getting up in their age.
- There's a lot of single
nucleotide polymorphisms.
We talked about APOE4 before previously,
but there's a variety of
genes that people have,
very common, actually.
In fact, I've had many
people that have done
that exact same thing.
So measuring your vitamin D levels
before and after supplementation
is the only way you're going
to figure that out, right?
Very important.
If you don't measure it, you don't know.
You can't know what you don't measure.
So there's a variety of SNPs
that basically make that
conversion inefficient.
And, in fact, there've been a lot
of these Mendelian randomization studies.
So these are studies where scientists
will look at commons SNPs,
people that have these
common variations of a gene.
That's more than 1% of the population.
So it's not a random mutation.
It's actually found in a sizeable
percent of the population.
And then, they've looked
at various outcomes.
And a lot of times, they'll look at genes
that are also involved in
some kind of lifestyle factor,
so vitamin D,
and SNPs that basically
make the conversion
of either vitamin D precursor into D3,
or D3 into 25-hydroxy vitamin D,
or into the active steroid hormone,
which is 1,25-dihydroxyvitamin D3.
And there's a variety of
different SNPs that show.
So you're not looking at
vitamin D levels at all.
You're looking at just the SNPs.
And you know, if they have
it, they have low vitamin D.
So it's really a way of doing
a beautifully randomized controlled trial
with an observational study
because you're not biased.
Vitamin D levels are also
associated with health.
People that have higher vitamin D
are either outside more,
they're more physically active,
or they're aware of their health
and their supplementing, right?
So you always have to worry about that
when you're doing an observational study.
Dealing in randomization is
beautiful for that reason,
where you're now just random.
People randomly have these genes,
and there's no health status.
If you have the SNP, like your friend,
like your family member
was healthy and all.
They were healthy,
and yet they couldn't get
their D levels up, right?
So these Mendelian
randomization studies have found
that people that can't
convert into the precursor,
the 25-hydroxy vitamin D, which
is usually what's measured.
It's the most stable form
of vitamin D in the body.
They have a higher all-cause
mortality, if they can't do it.
So people that don't have it
have a lower all-cause mortality.
They have a higher
respiratory-related mortality.
They have a higher
cancer-related mortality.
So, to me... Now, why
did I get on this rant?
Oh, because your family member.
So, basically, they also are more likely
to get multiple sclerosis.
This has all been done with
Mendelian randomization.
And so it really does
hammer home the importance
of measuring your vitamin D levels
and being very proactive about that.
I mean, you can get it done anywhere.
Your doctor will do it. You
ask 'em to do it, you know.
So supplementation wise,
typically, if you don't
have one of those SNPs,
for the most part, taking
1,000 IUs of vitamin D
will raise blood levels
by around five nanograms per milliliter.
So let's say you're deficient,
you're 20 nanograms per milliliter,
and you want to get to 40.
You're going to need at least 4,000 IUs,
if you are normal and don't
have any of these SNPs
that change your metabolism
of vitamin D, right?
- Does it matter when you take
it relative to sun exposure,
time of day, with or without food?
- I've seen some not so
great preliminary evidence
suggesting maybe time of day is important.
I don't think it.
Like, I can't seem to find
anything that really suggests.
Because for it to actually be
converted into the hormone,
I mean, it's stored.
- It's slow-acting.
These steroid hormones are slow-acting.
- Yeah, it's not like immediate thing.
So maybe we'll get some new
data that's like otherwise,
but I just don't, yeah.
- It simplifies the problem anyway.
So, for people who are
going to be stubborn
and not get their D3 levels
tested or their D levels tested,
and simply say, "Oh,
I'll just take some D3."
That was me, by the
way, until I got tested.
I threw 5,000 IUs into
the mix and figured,
well, it's not going to kill me.
It'll bring my vitamin D levels up.
I realize that's a bit of a
coarse way to approach it,
but I feel fine, and I'm still
breathing and ambulatory.
So, is that reasonable?
1,000 to 5,000 IUs for most
people will be reasonably safe.
Again, just assuming that people
are going to just jump to it
without the blood test.
- Of course, I think that,
if we look at the literature,
the scientific literature,
it is extremely hard to get hypercalcemia,
which would be the major concern
with really high levels of
vitamin D3 supplementation.
I mean, we're talking
like hundreds of thousands
of IU a day for a long time.
- Hundreds of thousands.
- Yes, yes.
Now, the upper tolerable intake was set
by the Medicine Institute to be 4,000.
It was kind of like one of
those things where it's safe.
I personally take 5,000 IUs a day as well,
and my levels really hover
around 50 nanograms per mill.
I don't put sunscreen on all the time.
I do put it on my face and I wear a hat,
but some of my skin is being exposed,
so I do make it from the sun as well.
- I'm glad you brought up the fact
that you keep arms exposed.
Because, in these studies
that I mentioned before,
looking at sun exposure on skin
and increases in other hormones,
testosterone, estrogen, mainly,
it became clear from looking at those data
that the amount of skin that
you expose is important,
which makes perfect
sense once you hear that,
but I think most people are thinking,
oh, I'm out in the sun,
but are you wearing shorts and a t-shirt,
or are you wearing a
sweatshirt and it's a hoodie?
Are you all covered up out in the sun?
Well, that might be great for
setting your circadian rhythm
by way of light through the eyes
'cause that's the primary
mechanism for that.
But seems to me that the
more of your body surface
that you can safely and appropriately,
please, folks,
appropriately expose to the sun,
the more vitamin D you're going to create.
So laying out on your back
deck in shorts and a t-shirt
with arms exposed and legs exposed
is a very different stimulus
than walking around in
jeans and a sweatshirt.
- Absolutely.
- Right? Okay, okay.
Especially if you have
sunscreen on your face.
I know it almost seems
like trivially simple,
but I'm not sure that
people are used to thinking
about their skin as a interface
to create these hormones.
- Yeah.
- So surface area matters.
- And by the way, there have
been studies looking at people
that are deficient in vitamin D.
In this case, it was African Americans
that were given a 4,000 IU
a day vitamin D supplement
to bring them back to sufficient levels.
This was a smaller
study than I would like,
but it reversed their
epigenetic aging by three years.
Because, again, it's a hormone.
It's regulating more than 5%
of your protein-encoding human genome.
There's been studies looking
at vitamin D receptor knockout mice.
And I use this a lot in my presentations
when I'm talking about
vitamin D and longevity.
If you look at these animals,
the vitamin D receptor,
as I mentioned earlier,
vitamin D binds to the receptor,
and then it complexes with
the retinoid receptor,
and they go into the nucleus as a complex
and turn on and turn off genes.
Well, if you get rid of that receptor,
which is what you can
do in animal studies,
you can determine what
effects there will be
with no vitamin D.
Like, how do you study no vitamin D?
And so what was found
was that these animals,
and, in fact, I don't think
it was a complete knockout
'cause I think it might
be embryonic lethal, but-
- [Andrew] Some hypomorph.
- Yes.
- Which is basically geek speak for a gene
is vastly reduced in its
function, number and function,
number, people know what I mean,
but isn't eliminated completely.
- Right, well, these animals,
if you look at them after
the age of four months,
I mean, the mice look like.
I mean, they're accelerated aging.
They're wrinkled. They have no hair.
Their lifespan's shorter.
I mean, you can look at this animal
and not know anything about
mice or work with them
and be like, "That animal
looks like it's..."
Of course, mice lifespans
are only like two,
two and a half years,
but, like, 500 years old.
- Looks like it went to
graduate school twice.
- [Rhonda] Yeah.
- Actually, graduate
school's a lot of fun.
I like to think I aged
backwards in graduate school,
which is not true.
I look at the photos. I
definitely aged forward.
You, on the other hand,
look exactly the same
way you did 10 years ago.
I'm not saying that to flatter you,
but it's absolutely true.
I mean, the data or the
data. It's remarkable.
So I'm definitely going to try
and get my omega-3 percentage up there.
I'm not going to hinge it all on that,
but clearly you're doing
a lot of things right.
So, if I'm taking vitamin D3,
I still need to get out into the sun.
Correct?
- Absolutely.
- Okay, I think a lot of
people don't know that,
or, at least, I have family members
that have been a little bit resistant.
Like, "I take my vitamin D
"so I don't need to get outside as much."
I think people are really afraid
of getting out into the sun
because they're worried about melanomas.
And, to be honest, I'm
as scared of sunscreen
as I am of melanoma.
Some of the things in
sunscreen are really spooky,
mainly the compound.
And here, I'm not one of these conspiracy.
I drink tap water. Listen, folks.
People cringe, but I drink tap water.
I have the occasional croissant or donut.
90%, 80% of the time,
I'm doing the right things,
the right way, I think.
Although, I'm now going to improve on them
with this new knowledge.
But I don't like what I
see in most sunscreens.
Because, if you look at these compounds,
they cross the blood-brain barrier.
I don't want compounds crossing
the blood-brain barrier.
- Titanium dioxide?
- Dioxide, some of the triclosans
that are also in these cleansers.
I mean, once you know a
little bit about neurons,
folks, you realize the neurons you got
are basically the ones you've
got for your entire life.
There's a reason why there's
a blood-brain barrier,
a blood-ovary, and a blood-testes barrier.
It's because the genetic material resides
in the testes, the ovaries, and the brain.
Those neurons don't turn over.
There are a few new neurons
but not that many unless
you're a mouse, frankly.
And so protecting those is very key,
and a lot of the things in sunscreen
are downright dangerous.
So I think there are
sunscreens that are safe,
but it's very hard to figure out
which sunscreens are
free of these compounds.
I'm amazed that they're
still on the market, frankly.
- I've always geared towards
the ones with the minerals
that are reflecting it.
It is somewhat difficult
to penetrate things
all the way through the skin
and get into the bloodstream,
but I don't know.
Maybe some of these compounds
get in there easily.
I have seen the evidence
with some of those things.
- Yeah, there is some
evidence they go transdermal.
- And they get in.
Okay, well, I know that some
of them react with the sun
and, while they do protect
from the UVA and/or B,
they form massive reactive
oxygen species and carcinogen.
I mean, it's like the
very thing you're trying
to protect yourself from
might actually cause-
- [Andrew] Right.
- We don't know. It's
completely speculation.
There is, I think, some more
and more evidence coming out
with some of those compounds.
I can't remember all of
'em off the top of my head,
but a lot of high-end ones also have.
It's the chemical sunscreen ones.
- Right, right.
- [Rhonda] The chemical ones.
- I'm proposing that we do a journal club.
A journal club, folks, is
where academics get together.
Well, they read papers,
then they get together,
and they pick apart the papers.
There's a strong correlation
between being an early graduate student
and being the most critical.
'Cause once you've actually
published some papers,
you realize that, most studies,
people are doing their best
within the context of what they can do.
But it'd be great to do a journal club
at some point about sunscreens
'cause I'd love to really figure out
what's in these compounds.
People are using them like crazy.
And I'm not one of
these people who's like,
oh, I won't use commercial toothpaste
or anything like that.
Like I said, I drink tap water.
I use commercial toothpaste, whatever.
But when it comes to
sunscreen, it freaks me out
because some of these
compounds do go transdermal
and some of them cross
the blood-brain barrier,
and I'd like to keep my
neurons free of that stuff.
Anyway, we're speculating now.
- Wear a hat.
- Wear a hat,
but get out in the sun
and get your D3 levels up.
Okay, so, we talked about
these plant-based compounds,
the omega-3s, and D3.
Unless there's something else
that you just absolutely
must throw into the mix,
I probably will return
us to the conversation
that I opened up with, which
was about cold and heat,
which, admittedly, I
pulled us off that path,
so I take full responsibility for that.
But before I do that,
I just want to offer you the opportunity.
Is there anything to supplement-based
or food-based compounds that
you think are especially useful
for brain and/or body health?
- I do think magnesium is
important in there as well.
I mean, I think, again, about
40% of the US population
doesn't get enough magnesium.
It's an essential mineral
we're supposed to be
getting from our diet.
- Involved in everything.
- It is. It's also involved
in vitamin D metabolism.
And, in fact, being deficient in magnesium
may make it more difficult
for you to actually
make vitamin D hormone,
so that 1,25-dihyroxyvitamin D.
So one of those other factors, again,
we talked about genetics,
but there's also magnesium status as well.
Considering 40%, that's a big number.
Now, magnesium's also
involved in making ATP,
the energetic currency of our cells.
Basically, all of our cells
need ATP to do anything.
It's also involved in utilizing ATP
as well as DNA repair enzymes.
These are enzymes that are involved
in repairing damage to our DNA.
I personally think that
magnesium insufficiency
causes an insidious type of damage daily
that you can't look in the mirror and see.
When you're deficient in vitamin C,
you're like, "My gums are falling apart.
"I have scurvy, right?"
But you can't see DNA damage.
You can't see it, but it's happening.
It's happening right now in my body,
and it's happening in your body.
It's happening. Normal metabolism
is happening every day.
But we repair that damage.
We have repair enzymes in our body
called DNA repair enzymes.
They require magnesium.
Magnesium is a co-factor for them.
What that means, a co-factor means,
enzymes need it to function properly,
and so, without that co-factor,
they're not doing it properly.
The way I like to think
about magnesium. It's easy.
'Cause people go, "What
food should I eat?"
Naturally, that's the next question.
Well, magnesium is at the center
of a chlorophyll molecule.
Chlorophyll is what gives
plants their green color.
So dark, leafy greens
are high in magnesium.
Basically, what does the 40%
insufficiency in the US tell us?
People aren't eating their greens.
They're not eating their greens.
They're eating their packaged food.
They're eating their processed food.
The standard American
diet isn't really high
in dark, leafy greens.
So dark, leafy greens are how
I like to get my magnesium.
I think it comes along with
all these other important.
I mean, you get calcium in
them. You get vitamin K1.
You're getting a lot of
other micronutrients,
and you're getting other compounds
that we don't know about,
and ones that we know about,
like sulforaphane, right?
- As with broccoli,
do I need to eat the
dark, leafy greens raw?
And, in this case, I'm
a little more open to it
because I actually like the
taste of, dare I say, kale.
And kale's a dark, leafy green, right?
- Yes, and it's high in
lutein and zeaxanthin as well.
- I'm a trichromat, meaning
I'm not color blind,
but I just want to make sure it falls
under the strict category.
'Cause every once in a while, I'm like,
"Oh, I eat my vegetables."
I like avocados,
and people remind me
avocados are not a vegetable.
I love vegetables also.
So kale, what are some other examples?
- Kale, spinach, chard, like
Swiss chard, rainbow chard,
romaine lettuce.
- Is the bitterness an
important component to this?
- For magnesium, no, but for sulforaphane,
for cruciferous vegetables.
That would be the brassica family.
But your question about cooking them.
So magnesium, it is
bound to the food matrix,
and it can be somewhat less bioavailable.
So cooking it can somewhat
release the magnesium,
but it goes into the water too.
So you have to either steam it
or kind of like get your water in.
- You can drink the water.
- Yeah, I personally don't worry about it.
- Okay, great.
- [Rhonda] I just don't worry.
- Well, if you don't worry,
I'm not going to worry.
- But I also do supplement with magnesium.
So supplementation with magnesium,
I mean, we could go on and on.
Let's keep this short and sweet
because we're going to get
back to the other stuff.
But it can cause GI
distress at high doses.
I personally like to take
around 130 or 135 milligrams.
That way, it's not like
a huge bolus to my gut.
- But I think it depends on
the form of magnesium too.
- Yes, yeah.
I mean, you can take magnesium
threonate, for example,
and it doesn't affect the gut as much.
- Magnesium citrate.
- Citrate is what I take.
- [Rhonda] I take Thorne.
- It's a pretty potent
gut stimulus.
I feel like it's a little
bit harder to digest.
- 135 milligrams should be pretty good.
And citrate, actually,
oh boy, do we want to go here?
- I mean, it's up to
you. We don't have to.
Personally, I've been
supplementing with magnesium
for a long time.
I use threonate and bisglycinate
and malate for different reasons.
So, yes, I would love to
go there if you're willing.
- I would say malate would be the best,
and that has to do with
the short-chain fatty acids
being good for the gut
and a lot of work done
by a former colleague
of mine and good friend,
Mark Shigenaga, showing that
the short-chain fatty acid,
citrate, malate, lactate,
but specifically malate,
really, and lactate
are the major ones that get
into the gut epithelial cells
and are an energy source
for the mitochondria
and the goblet cells, so anyways,
whole other topic.
- That's okay.
I take malate because I was
told that it would be helpful.
First of all, it doesn't make me sleepy
like some of the other forms of magnesium,
which act as a mild sedative for me.
They do tap into the GABAergic pathway,
a neurotransmitter, folks,
that, in general, broad
sweeping generalization here,
can have somewhat of a sedative quality,
which is why I take magnesium threonate
and/or bisglycinate before sleep,
30 to 60 minutes before sleep.
Definitely enhances my
transition time to sleep
and the depth of sleep.
No question, in my experience.
There's some data that threonate
can be neuroprotective,
although those studies are still ongoing.
I'm getting the sense that maybe you're
a little more skeptical of that than I am.
- Yeah, no, I've seen the
studies with the threonate.
I think, looking at the actual data
from the one clinical study,
there wasn't statistical significance
until all three of the pieces
of data were pulled together,
but that really could just
be because their sample size
was too small, right?
- Yeah, I'm thinking that paired with the,
there's some work-
- [Rhonda] The animal stuff.
- Yeah, Guosong Liu's work on.
This is getting kind of
inside ball of neuroscience.
The quality of the labs matters, folks,
and that's something that's not accessible
to people outside of fields.
Guosong Liu and some of the
other folks at that time at MIT,
I think very highly of their work.
And so the animal studies are
indeed just animal studies,
but I was pretty impressed
by what they did in those studies.
Very pioneering when you
think about this being done
10, 12, 15 years ago.
And then, yes, we need
more human clinical data.
But, for me, I figured that,
given the safety profile
of mag threonate, given that
it helps me sleep better,
and sleeping better is just
better for everything, frankly.
That's why I take it.
And bisglycinate and threonate
seem to be somewhat interchangeable,
but I don't know of any reports
that bisglycinate can be neuroprotective.
But malate I take during the daytime.
For me, and, again, this is subjective,
it has a tangible effect
in improving the recovery
time from exercise.
I don't know that I've
been sore from a workout
since I started taking malate,
and I used to get very sore
from even kind of trivial workouts.
So I don't know what's going
on there, but I keep taking it.
- Malate, again, the
short-chain fatty acid,
and when you do intense exercise,
you release endotoxin from your gut.
I'm just going back to
the interesting work
'cause the malate being
the short-chain fatty acid
and Mark Shigenaga showing,
this is all an animal research by the way,
but it was feeding these animals malate.
It really protected the
gut, endotoxin release,
and it affected metabolic
syndrome and all sorts of things.
But I think malates awesome,
and I always try to eat green apples.
They're really high in malic acid.
- [Andrew] Oh, good to know.
- And tart cherries.
Tart cherries are really
high in it as well.
- They also taste really good.
- But I was really interested
in the magnesium threonate stuff.
I take a supplement called
Magnesi-Om by Moon Juice.
And it's like a little powder.
It's got a little bit of monk
fruit, but it tastes good.
So I do it a little bit
before bedtime as well.
Probably several more hours though
because I don't like to
drink tons and tons of fluids
before I go to bed.
And it has magnesium threonate,
and a variety of other versions
of magnesium in it as well,
and I really like it.
But I thought the
magnesium threonate stuff
was super interesting.
I would love to see more
clinical data as well,
but I think, once we get
it, it'll probably be like,
oh yeah, it's getting into
the brain, and it's awesome,
so, you know, why wait?
- And along those lines,
I once put out a post that said,
I feel like there are a
number of different categories
of health information consumers online
and understanding which one
you're in for which topic
can alleviate a lot of
the strain and stress
of finding the information.
There's some people that
are perfectly comfortable
with data from a mouse study.
It's like, "If it's done in
mice, great. I'll try it."
Other people say, "No, it
has to be done in humans."
Double-blind, placebo-controlled studies.
Randomized clinical trials, et cetera.
Then, other people just
say, "You know what?
"I don't even care about any of that.
"Just tell me what you do."
And then, other people
say, "You know what?
"I don't even care what you
do. Just tell me what to do."
And then, there's this other category
which are, if it's in
pill form or powder form,
they'll take it.
And so I think a lot of the battles
of people picking apart
people's posts and things
have to do with the fact
that people don't realize
that people are showing up to the table
in one or some combination
of those stances.
We know people that will try anything,
and we know people that
won't take anything.
So the idea here is to create
an array of possibilities
for people, and I think the
animal data are very impressive.
We should have you back on to talk-
- I take it with the hope of,
because I feel like the animal data
is very promising.
- Right, there you go.
- And so I'm like, it
probably is, so why not?
- Well, and obviously
you're doing things right.
So cold and heat
converge on some common pathways
related to what you called
intermittent challenge,
which I love.
I think, intermittent
fasting, cold, heat, exercise,
I mean, maybe even
intermittent sleep deprivation.
I keep waiting for the intermittent
sleep deprivation movement.
I will say, I pull a few
all-nighters per year
just for work demands and
procrastination and deadlines.
I'm the worst combination of academic
'cause I'm both a procrastinator
and a perfectionist,
so you end up pulling some all-nighters.
The sleep I get the next
night is pretty amazing.
I must say, it's the sleep of gods,
but I don't recommend anyone
use sleep deprivation for that.
But I could imagine that we also evolved
having some sleepless nights.
So this idea of intermittent challenge
is a really attractive one,
and I want to make sure that we credit you
with the phrase intermittent challenge.
- No, credit Dr. Mark Mattson.
- Okay. Dr. Mark Mattson gets credit.
- Who's published,
and he has used that-
- He used those words.
- Oh, that phrase.
- Yes.
- Okay, great. We'll make sure.
- Just like Dr. David Sinclair,
I love the xenohormesis.
It was in one of his
publications so many years ago,
and I just love it.
Brilliant. A brilliant term.
So Mark Mattson gets credit.
- Those Harvard guys
are pretty smart.
I mean, it's a good school, I guess.
Of course it's a good school.
We will credit the appropriate people.
Thank you for that clarification.
So you've talked a lot about the use
of what I call deliberate cold exposure,
only to distinguish it from cold
that you might just be
accidentally exposed to,
but it's sort of obvious
when we say cold exposure.
There are some amazing data on cold.
The other day I saw a post from you,
and you've included this in talks before.
I did not know this until
I learned it from you,
so credit to you,
that even 20 seconds of immersion in,
I think, it was four degree.
- 49 degree Fahrenheit.
- 49 degree Fahrenheit.
Okay, I was translating to Celsius,
but 49 degree Fahrenheit
water, so cold water,
can lead to long-lasting increases
in epinephrine, adrenaline,
and I have to presume
other neuromodulators
and neurochemicals as well.
What are some cold protocols
that you find particularly
interesting or attractive
from the standpoint of, I
dunno, pick your favorite,
metabolism, neuro/mood effects,
brown fat stimulation,
which, of course, weaves
back to metabolism.
We could do an entire
episode all about cold,
but what I'd love to know is,
what sort of activity
or stimulus do you think
is a reasonable and
particularly potent one
to use in terms of cold?
- So, today, I did three minutes
at 49 degrees Fahrenheit.
I have a cold tub.
- So you get in up to your neck?
- Well, I try. I keep floating up.
It's like really hard.
I would say maybe most of my shoulder.
I mean, really I'm floating up.
I was telling my husband.
I was like, "There's too
much water in here for me."
- Or too much salt in there?
Is it like the Dead Sea
where you float on top?
- Is there salt in there? I don't know.
He takes care of all the
stuff that, you know.
It's the Plunge.
- By the way, the podcast
nor I am sponsored by Plunge.
They did give me one.
That thing is fantastic.
Also, 'cause it circulates the water.
- It does.
- Which makes sure that you
break up the thermal layer,
and it's even colder.
- It is even colder. It sucks!
Anyways, so look,
I'll be honest here.
I wish I did more cold than I do.
I do cold when I'm going
to go on a podcast.
I definitely do cold when
I'm going to do a podcast,
when I'm going to give a
talk or when I'm anxious.
I need to make it more of a ritual.
I love doing the sauna. I hate the cold.
I hate it, unless it's summertime.
It's a lot easier for
me to get in the cold
in the summertime.
But what I do love about the
cold is how I feel after.
And I feel less anxious.
I feel good.
I feel more focused, which
is why I'll usually do it
before any type of public speaking,
or when I'm just anxious,
I'll just get in there.
And so the 20 seconds at 49 degrees,
I think it was 49 degrees Fahrenheit
was really a good number
because time and temperature,
time, or duration, I guess,
would be a better word,
and temperature do matter,
but you can do 20 seconds
at a colder temperature,
which is I prefer,
or you can do a minute or
longer at a warmer temperature.
I think there was another study
showing 59 degrees Fahrenheit at one hour
was like two to three, but
who wants to do one hour
at 59?
- Yeah, I'm familiar
with that study.
So this really reveals just
how absolutely nerdy I am
and maybe why some times and relationships
in my life were challenged.
I love reading the method
sections of papers.
So people can come at me
with a number of things
about papers, and I might miss something.
Surely I miss certain
things, like anybody does,
but the methods I relish
in reading the methods,
and that paper is really interesting
'cause they had people sit
in lawn chairs basically
in swimming pools for an hour.
It was chilly. It wasn't super cold.
I mean 60 is not.
It's not warm, but it's
not ice-cold obviously.
But an hour is ridiculous at some level.
But the increases in dopamine
were massive and lasted hours.
So the mood enhancing
effects that you report,
you're not imagining that.
Those are almost certainly a consequence
of having slowly elevating
but significantly elevated
dopamine that goes on for hours.
That's almost a dreamlike
profile for dopamine.
Because most everything else,
like an Adderall or Ritalin,
a cup of coffee and a
pre-workout drink or something,
is going to give you a big
spike in adrenaline and dopamine
and a big crash.
And somehow, it creates this
really nice, contoured profile.
So whatever you're experiencing there
is very nicely supported by the data.
- Well, I need to get doing it more.
I've had a couple of scary experiences
going from hot to cold.
- Can you explain?
- Blood pressure changes, I think,
where I basically went straight
from a really hot jacuzzi.
I was in there for like 30 minutes.
I was doing heat stress.
- Jacuzzi, okay.
- Yeah, 104 degrees Fahrenheit.
- [Andrew] That's toasty.
- For 30 minutes, and
then I went straight into,
at the time, it was our pool,
it was in February, it was
wintertime, and it was 50.
It was in the 50s. It was cold.
And I was in there,
and I was listening to
Simon and Garfunkel,
I was trying to stay in a
long time, get on my cold,
and I was trying to impress Dan
'cause he'll stay in
there for like 15 minutes.
- [Andrew] Wow.
- But I started to feel really blinkey,
like low blood pressure or something,
and I got scared, so I got out,
and then I couldn't stand, like
I had vertigo or something,
and I was so scared.
I was so scared.
And I've had a couple of times too
where just going straight
from the sauna to it,
to the Cold Plunge, where I'm
starting to feel, I'm like,
ooh, I feel a little blood
pressure change or something.
It makes sense.
The sauna is causing
vasodilation and the Cold Plunge
or cold exposure is
causing vasoconstriction,
so it's like a very
just shock to my system.
And so, now, I wait.
I wait like a few minutes before going in.
But I do need to kind of like
make the cold more routine.
Because I talk all about the science.
I'm familiar with all the science,
and the norepinephrine or noradrenaline,
it's affecting brain and mood.
You know way more about that than I do.
I know how I feel,
and I know it's a neurotransmitter,
and it is released, at least,
in rats, they've shown.
Or was it mice? I think
it might've been rats.
But multiple studies
showing that it's released
from the cold in the brain.
- And now, in humans as well.
- Oh, in the brain, they've shown.
- So, in that study, we
could put a link to this,
it's published in 2000 in
European Journal of Physiology,
that big dopamine increase.
They also looked at
epinephrine and cortisol
and saw some really.
Yeah, so this has been done.
- They did brain. Oh-
- [Andrew] Oh, no, no-
- The plasma, yeah.
Yes, plasma.
- Very hard to measure
dopamine directly from the brain
unless you're doing microdialysis.
No, unfortunately,
unfortunately, their skulls were intact.
Fortunately, for them,
unfortunately, for the research community,
their skulls were intact,
so they couldn't measure
directly in the brain.
But obviously, there's a correlate there.
It's a very real effect.
But the advantage of
not doing it too often
is that you're not cold adapted.
Now, it's very hard for anyone
to get truly cold adapted.
Some people start to
look forward to the cold.
And what I think they're
looking forward to
is the feeling afterward,
that dopamine rush.
But, if you get cold adapted,
then it certainly blunts
some of the effect.
- But I want to be cold adapted
because that means I
have more mitochondria
in my adipose tissue
and perhaps even muscle.
That's been shown.
- So maybe there's a good opportunity to,
so cold and UCP1, if you
could educate us on UCP1.
I find this really interesting,
and I learned about it from you.
- Yeah, well, so norepinephrine
actually released in the plasma.
It does act as a hormone.
Vasoconstriction is one thing it does,
but it also regulates a
variety of molecular functions
that have to do with adaption to cold,
one happening to be,
shivering is a very inefficient
way to produce heat,
which is what your body's trying to do
when it's exposed to cold,
and your muscles are basically contracting
and producing heat from that,
but that's just not very efficient.
So the more eloquent way to do it,
or elegant, I guess, way to do it
is to basically have your mitochondria
produce tons and tons of heat.
So the way it does this
is by activating a gene
called UCP1, uncoupling protein 1.
Norepinephrine is upstream
of that, activating it.
What that does is, essentially,
so mitochondria are
these little organelles
inside of your cells
that are responsible for producing energy.
Usually, that's in the form of
adenosine triphosphate, ATP,
and that's what lets everything function
inside of your body,
from your neurotransmitter production
to your heart beating, et cetera.
However, you can uncouple
your mitochondria.
Basically, your mitochondria,
they're like a little
battery, so they have,
well, they have a double membrane,
first of all, their structure,
but they have a negative
charge on the inside,
and they have a positive
charge on the inner membrane,
so in between the outer
membrane and the inside part.
- Like a neuron.
- Like a neuron, yeah.
- [Andrew] Yeah, cool.
- So I guess,
it's like a neuron.
It's like a battery,
negative and positive.
Well, basically, you can
uncouple that charge,
and so that positive charge proton
start leaking out of the mitochondria,
and your mitochondria freak out.
So this is called uncoupling it.
It's maximum respiration, as we call it.
They try to make as much energy.
They're like, "I got to
get that proton back,
"that gradient, electrochemical gradient."
And so they just go insane.
In this case, it's uncoupled energy,
so the energy they're making
is actually heat, not ATP,
but you're essentially burning
substrate, so who cares?
You're burning glucose.
You're burning lipids.
You're basically burning
things and making heat.
And so that's what uncoupling does,
and that is a much more efficient way
of producing heat than shivering.
So, as you become more adapted,
maybe the longer duration
that you've stayed in the cold
or the more times you've done it,
you'll no longer shiver anymore.
You will start to then just
do this uncoupling type
of thermogenesis, as it's called.
And another type of adaptation that occurs
is you actually produce more mitochondria
in your adipose tissue.
And that actually happens,
also regulated by
norepinephrine or noradrenaline,
through a protein called PGC-1alpha.
And what that protein does
is it makes more mitochondria
in your adipose cell.
So, per adipose cell, you're
getting more mitochondria.
It's a beautiful way to
basically make more heat.
It's one of those things where it's like,
your body's going, "Okay,
I'm going to be exposed
"to this cold next time.
"How can I make sure I don't die?
"Oh, I can have more mitochondria,
"and I'm going to make more heat."
And so you're making more mitochondria
in your adipose tissue.
And this is often referred
to as the browning of fat.
And the reason for that is because,
if you look under a
microscope at a lipid droplet,
basically, a fat cell,
not a lipid droplet, adipocyte,
you'll find that it looks darker
because there's more
mitochondria in there.
So it's referred to as browning fat.
I don't want to get into
the whole beige fat, brown.
You know, there's this whole,
I'm sure you've had experts
on that talk all about that.
- No, not yet.
I always think of white
fat, beige fat, brown fat.
And beige is kind of,
white can be converted into beige.
- Right, and beige can take on
thermogenic characteristics essentially,
and so you can activate beige
fat so that it's thermogenic
in the sense that it's burning
glucose and/or fatty acids
and producing heat.
So the more you expose yourself to cold,
the more you can brown
your fat, so to speak,
and therefore you can tolerate
the cold for longer periods,
which people do notice,
and you can then have
the thermogenic qualities
of having more brown adipose tissue
or beige, activated beige, adipose tissue.
You'll get a lot of
naysayers out there saying,
"Oh, brown fat doesn't
regulate metabolism at all."
And the reality is there's
thousands of researchers
trying to pill up brown
fat and thermogenic.
They're trying to make it a pill
because it does affect metabolism.
It's not the only thing.
It's certainly, if you're obese
and trying to lose weight,
you're not going to do that
just by doing cold exposure.
You need to do dietary and
exercise changes predominantly,
but it does affect metabolism.
And this has been shown in human studies,
so it is an interesting,
it's another possible mechanism
for affecting metabolism,
and that's an adipose tissue,
but you also make more
mitochondria and muscle tissue.
And this is regulated,
not via norepinephrine,
but it is still PGC-1alpha, interestingly,
not that anyone else really cares but me,
and maybe you do, Andrew.
- I'm eating this up.
- So PGC-1alpha responds to norepinephrine
in adipose tissue to
make more mitochondria,
but, in muscle tissue, it's
unclear what the regulator is.
Cold exposure does it.
So this was shown at least in
a couple of studies I've seen,
where people that were
exercising, I believe,
or maybe it may have been men
only that were exercising,
did some training, and then
did cold water immersion,
something like 50 degrees
Fahrenheit, 15 minutes,
and PGC-1alpha, which is a biomarker
for mitochondrial biogenesis,
which is the generation
of new mitochondria.
By the way, that's awesome.
You want more mitochondria in your muscle.
It's associated with improved muscle mass,
improved endurance.
Mitochondria are essentially,
they're making energy in your cell.
We don't make more mitochondria normally.
You have certain inputs,
high-intensity interval
training, exercise can do it.
- Can actually make more mitochondria.
- Yes, yeah, and that's
been shown in people.
- Weight training or just
high-intensity interval training?
- I haven't seen weight training.
I've seen it in high-intensity
interval training,
endurance training,
but that doesn't mean
that it hasn't been shown,
I just haven't seen it, or
that it hasn't been looked at.
- That's good to know.
I'm always looking for reasons
to finally do more HIT type,
high-intensity interval training work.
I do weight training, and
I do low-intensity cardio.
- There was a brilliant study by,
at the time, he was a
postdoc, Matthew Robinson,
and he's now gone on to start his own lab
at the University of Oregon
Health Science Center.
- [Andrew] Great place, yeah.
- And he did a study where
both young and older people,
they had this whole
high-intensity protocol,
which I can't remember what it was,
but their protocol for X amount of time.
I'm sure it was at least a month.
They then measured biomarkers
of mitochondrial biogenesis
in their muscle tissue,
and the amount of mitochondrial biogenesis
in old people specifically,
it happened in both
young and old from HIT,
from the high-intensity interval training,
was, I mean, it was enormous,
at least 50%, I think.
- [Andrew] Fantastic.
- So it was just like, whoa!
And so, why would you want that?
Well, mitochondria,
your cells are turning over.
You make new cells. You replace old ones.
With your mitochondria,
you don't really do
that for the most part.
You can.
Mitochondrial biogenesis does happen,
but you have to stimulate it to happen.
And what happens with your mitochondria
is they essentially are bobbing
around inside of your cells,
and then they fuse with
other mitochondria,
exchange all their
content, mitochondrial DNA,
and then fizz back apart.
And that's how they
kind of stay young-ish.
But, as you age, you keep doing that
with the same pool of mitochondria,
then you're going to get a
bunch of old mitochondria
mixing old stuff together, right?
So, why wouldn't you want
to bring up new, healthy,
young mitochondria into that pool, right?
So, in my mind, when I hear
mitochondrial biogenesis,
I'm like, aging.
That's the first thing I think of.
So, anyways, cold exposure does that.
Other things as well, so.
- Amazing.
And please, thank you for offering
to somehow filter the level of detail,
but I assure you that
listeners of this podcast
are familiar with drinking from
the fire hose of mechanism,
and that was really helpful.
And, again, this is just
one example of maybe four
or five other things that
you've said, at least,
that are going to inspire
me to change my behaviors.
I'm going to start doing some
high-intensity interval training.
Dr. Andy Galpin was on
this podcast recently,
and he told me that the
subtle zone 2 cardio
and the weight training's great,
but that I really should be doing
some max heart rate work per week,
going into max heart rate for 90 seconds,
then resting and repeating
that, maybe even mild repeats.
I'm just curious, as a brief aside,
before we talk about heat,
what sort of cardiovascular
or other types of training do you do?
Do you do HIT?
I imagine you are doing
high-intensity interval training.
If you could just give
us a sense of the contour
of your week as it relates to exercise.
Because you've been very gracious
in sharing some of what you
do for supplements and food,
what about exercise?
- So it all depends on my week, of course,
and what I've got going on with
my son and my work schedule.
But I do a lot of
high-intensity interval Tabatas
on a stationary cycle.
I use Peloton because I just
like that instructor there
telling me what to do,
and then me competing with everyone else.
I'm like, ah, you know?
So it works for me.
- You're revealing something
about your psychology.
This is good. We just learned about.
So this podcast is actually just a decoy
for psychological assessment of the guest.
No, I'm kidding.
So, now, we know you're competitive.
Good.
- [Rhonda] Yeah.
- That explains a lot of how
you got through graduate school
and then do what you do.
So you're getting on the Peloton,
and what does it look like
for someone who's not
familiar with Peloton?
I know what they are, but
I've never been on one.
You're pedaling against the
instructor for how many seconds?
- So there's a bunch of
people that are online,
either doing the class with you
at the same time or all time doing it,
so you can kind of
toggle on what you want,
and you can try to compete
against the all time number.
- So it's really competitive.
- [Rhonda] Oh, yeah.
- Okay.
- And the instructor is just
there to, like, whip you.
You know, make you.
The brilliance with Peloton is...
I used to do what's called rush cycle.
It's basically you go in and group cycle
and have an instructor there,
and you do all this high-intensity
interval training stuff.
And I loved it because there
was a competitive aspect to it
that had me working
harder than I would work
if it was just me in the room,
like without an instructor
or anyone there,
and it was just like,
I'm at a gym, any gym,
and I'm just on a stationary cycle
listening to a podcast, doing something,
which is fine if that's
your groove, right?
But there is something
about that group setting
that kind of holds you
accountable too, right?
And the Peloton made it somehow
virtual. It was amazing.
And I remember being back at rush cycle,
this is before pandemic,
and people talking about
Peloton in my class,
and I'm like, "Oh, that's
ridiculous. Why would I do that?
"That's never going to
work. I need to be here."
And then, the pandemic hit and
I was all over the Peloton,
and it works for me really well.
So I tend to do that at
least three times a week.
Sometimes I do it more, like I'll do four.
And I do a 10 minute, just 10,
because it's efficient, and I push my ass.
I push myself really hard.
- That's the Tabata.
- It's 20 seconds on, 10 seconds
off, and it's 10 minutes.
- And on means you're pedaling
like your life depended on it.
- [Rhonda] You're maxing it.
- And there's a lot of
resistance in the pedals?
- I always do resistance.
I like the power. I do the power.
There's a part where
you're sitting cycling,
and you're trying to go really fast,
but I always crank the resistance up.
I always go above what they give me.
And then, there's a part
where you're standing,
and then you really
crank the resistance up,
which I really do, and you
feel it in your glutes.
- It's like going up a hill.
- Yeah, exactly.
And so they break it up,
and most of the time you'll
have those two parts.
And I love the efficiency of it.
You get it done.
And people sometimes
hear me, go, "10 minutes?
"Oh, really? You think you work?"
I'm like, look, you do
max Tabata for 10 minutes,
and it's intense.
- Yeah, most people
can't sprint for the gate
of an airplane they're about
to miss, carrying a backpack.
So, if I think about that,
and I've just described myself,
sprinting through the airport and going,
"All right, Andy Galpin,
"I got my 90 seconds max
heart rate in for you,
"carrying this thing."
But 20 seconds on, 10 seconds off,
repeating that over and
over for 10 minutes,
so, by the time you're
done, you're cooked.
- And then, because I'm competitive
during the recovery that
they give you at the end,
I'm pushing it max, so I
get the numbers higher.
- Great.
So three times a week.
- [Rhonda] It's a trick.
- Yeah, three times a week,
and then I always have my
sauna on preheating up,
takes about an hour and a half,
and I get it to about
189 degrees Fahrenheit.
I hop right in the sauna after my Peloton.
- So the elevated heart rate continues.
Is that the rationale?
- Yeah, I literally down a bunch of water,
and then I get in,
and then I either read a science paper,
prepare for a presentation or a podcast,
or I hash over things in my mind.
And it's interesting
because something about
getting in the sauna,
I think the stress, the heat stress of it.
So I started doing the sauna
in 2009 in graduate school.
- You're an early adopter.
- I started doing it every
day. I lived across the street.
I lived in a studio apartment with Dan.
We lived in this small studio apartment,
smallest apartment you could ever imagine,
and it was across the street from a YMCA,
'cause I was poor in graduate school,
very poor, very poor.
- I recall. I lived in my lab.
- Wow, really?
- But, then again, I lived
in my lab as a postdoc.
I admit, I lived in my lab with my bulldog
as a faculty member for other reasons.
But I get it.
When you're a graduate student,
you're poor, basically.
- Yes, and so I used to go to the sauna
before going into the lab,
and I started noticing that
I was, all of a sudden,
able to handle stress better,
like the stress of my six-month setback
because of a failed
experiment, which is crushing,
on top of the pressure from
my advisor and my own pressure
'cause I'm very competitive with myself,
and I put a lot of pressure on myself.
So I was having a hard time.
I was very stressed
out in graduate school.
And this sauna started to
really noticeably affect
my anxiety and my
ability to handle stress.
And I was like, what is going on here?
So I started looking into the literature
and started getting interested
in the effects on the brain.
And, in fact, at the time, I had a friend
who was not actually experimentally
but theoretically looking
into the opioid system.
So, when you get in the sauna,
you release a lot of endorphins.
Endorphins are the feel-good opioids
that make you feel good,
but you also release
something called dynorphin.
And dynorphin is an endogenous opioid
that binds to a receptor called
the kappa opioid receptor.
Dynorphin is responsible
for that dysphoric feeling
when you're in the sauna and you're hot,
and when you're running, doing exercise,
and you feel uncomfortable.
Well, I think that's dynorphin.
I'm speaking absolute,
but I think it is.
- No, I think it is.
I mean, there's evidence in alcoholics
that some of the symptoms of
withdrawal that they experience
are related to dynorphin.
And dynorphin is known
to negatively impact
the dopamine receptor system.
So, basically, it's the
feel-like-garbage pathway.
- Right, you feel like garbage,
and so you think that
that would not be good,
but this is where my friend comes in.
He was looking at the effects
of treating morphine or heroin addiction.
And people that are using those drugs,
they, basically, the endorphins
or the morphine or heroin,
they bind to a receptor in the brain
called the mu opioid receptor.
And, as they take these drugs,
that mu opioid receptor
becomes downregulated,
and so you need more and more of the drug
to feel as good as you did.
Well, endorphins also
bind to that receptor.
And he was looking into
some of the other drugs
that are like salvinoria,
salvinorin, or something.
Salvia it's called. It binds
to the kappa opioid receptor.
It also makes you kind
of feel uncomfortable.
Anyways, he had put some
studies in front of me
that showed basically
binding of either dynorphin
or whatever ligand to
the kappa opioid receptor
basically sensitizes
the mu opioid receptor
to the feel-good endorphins
and also changes,
I think it also upregulates
it or something,
so, basically, there's a
lasting effect of feeling good.
So the endorphins that you release later
from hugging someone,
or a joke you're laughing at, or whatever,
you feel it for longer, right?
And so, anyways, with
respect to the sauna,
it's a big sort of hypothesis of mine.
I did kind of publish
that part of my hypothesis
in a review article, but
I do wish more people
would kind of look into that.
That'd be amazing.
But what I was getting at, I think, was,
I would use the sauna to memorize things.
This is way back in the
day, and I still do it.
And I wanted to talk to you about this
because you're a neuroscientist,
that there's something
about being in the sauna.
And I don't know if it has to
do with the stress response.
Like, when you have an emotional trigger,
you remember things better, right?
- Absolutely.
There is a clear and known
explanation mechanism for this.
- So, in the sauna, you
also release norepinephrine,
just like you do in the cold.
There's a lot of overlap.
It is a stressor, but I
use it to remember things.
Like, I'm going through something.
I want to go through a
presentation, or a talk,
or a podcast, or whatever.
And I go in that sauna.
And you should try it,
if you haven't already.
I don't know if you have.
- I have a sauna and Cold Plunge now,
and I haven't tried preparing.
I read books in the sauna in the evening.
It's a time I insist on
having my phone out of there,
initially because I
thought I'd cook the phone,
but also just to get some separation
from the phone and screens in
the evening, so I read books.
The only challenge,
sometimes you're dripping
sweat onto the books,
but I'm willing to forego
a few pages of a book.
The idea that being in this
semi-stressful environment
would aid in the learning
and retention of information
is really well substantiated.
There's this beautiful work
by a guy named James McGaw.
I don't know if his lab's still active,
but he was at UC Irvine for a while,
and then I think at
University of Arizona as well.
They have a great memory
group at both places,
very strong in learning
and memory, both places.
And he was the one that really defined
this kind of inverted, u-shaped function
for the relationship between
adrenaline and memory.
Basically, if you're too
relaxed and not stressed enough,
you're not going to
remember any information.
At peak levels of stress, you
actually are a memory machine,
at least within the context
of whatever it is you're trying to learn.
So what you're describing
very well matches with that.
Then, of course, it tapers off
as you really increase
adrenaline to the point
where people are starting
to lose autonomic function,
where they're panicking basically,
but obviously, you're keeping it in range.
The other thing that I would
like to ask you about is,
in the sauna, of course,
there's vasodilation,
and perfusion of blood to
the brain is a wonderful way
to enhance cognition.
There's even some really
nice data showing that,
during inhales as opposed to exhales,
people are better at learning information.
Believe it or not, during the inhale,
you're taking in and absorbing
and remembering more than during exhales.
And these are beautiful studies
done in humans, of course.
So I can imagine that vasodilation,
getting more perfusion
of blood to the brain,
plus a little bit of stress,
or maybe a lot of stress
from the epinephrine,
and then, of course,
there's going to be the,
I don't want to call it placebo,
but there's going to be the context,
the condition, place context of it.
Like, if we had a good experience
remembering something in the sauna once,
the positive association effect
of that location is real.
Just like, if people go to a
new city and they get robbed,
like, if you go to Cincinnati,
I've never been to Cincinnati,
but you get robbed in Cincinnati,
your purse gets taken or
your wallet gets taken,
you kind of hate Cincinnati as a tourist.
But that could happen in any number
of different cities, right?
The opposite is also true,
so if something good happens someplace.
So I'm imagining that it's a
combination of those effects,
but it would be very hard
to do this in the cold.
I feel like the cold is a very potent.
I think it takes you
too far down that curve,
the McGaw curve.
- I have to sing songs or
something when I'm in there.
- [Andrew] Distract yourself.
- Oh yeah, I sing songs.
- But afterward, you're
very efficient at learning.
- After I am.
With respect to the sauna,
the vasodilation does occur,
so there's a lot of overlap
between moderate-intensity
aerobic exercise and heat stress.
As you can imagine,
when you're exercising,
you're elevating your
core body temperature.
You're sweating.
When you're actually in the sauna,
blood does get redistributed to the skin
to facilitate sweating,
but, much like exercise, blood
flow in general is improved
to the brain, to the muscles, everywhere.
So, I think, generally speaking,
and there's studies showing
that sauna use is associated
with a much lower risk of
dementia and Alzheimer's disease.
People that use it four
to seven times a week
have greater than 60%
reduction in dementia
and Alzheimer's disease risk
compared to once-
- Amazing, how many?
Oh, sorry, I didn't mean to cut you off.
You said people who use it,
I apologize, but maybe
you could tell us again,
people use it four to seven
times per week have...
- They have a greater than 60% reduction
in dementia risk and
Alzheimer's disease risk
compared to people that use
it only one time a week.
People that use it two
to three times a week
have something like a 20,
a little greater than
20% reduction in risk.
There's a dose-dependent
effect on dementia risk
and Alzheimer's disease risk.
It also has a profound.
There's a big link
between the cardiovascular
system and the brain.
Obviously, blood flow, a big one, right?
You need to get blood to your brain.
But cardiovascular mortality,
so mortality from cardiovascular disease.
If people use, or actually this was men.
If men use the sauna four
to seven times a week,
it's a 50% reduction in
cardiovascular related mortality
compared to one time a week.
Again, dose-dependent manner,
two to three times a week
is something like 24% lower death
from cardiovascular disease.
There's also lower sudden cardiac deaths,
like a heart attack.
That's like 60 something,
greater than 60% lower,
if men use it four to seven
times a week versus once.
Again, a dose-dependent thing.
The thing that's so
profound there also to me
when, again, looking at the methods,
when I look at the data,
and this is all work
from Dr. Jari Laukkanen.
He's in the University of Eastern Finland
and just one of the world
experts on sauna use,
especially with respect
to cardiovascular health.
What some of his data
has also shown is that,
if you look at the duration,
the time spent in the sauna,
so I mentioned the
temperature I do is about,
I do 189 degrees Fahrenheit.
Typically, I go in there.
I'm pretty heat adapted.
So the more you do the sauna
or any sort of heat stress,
whether it's a hot tub or
jacuzzi, you become adapted.
You basically start to sweat
at a lower core body temperature
to cool yourself down.
All these sort of physiological changes
start to happen earlier.
And so, I stayed in for like 30 minutes,
so I stayed in a long time.
That's a lot. You have
to listen to your body.
Most of the studies that
I just talked about,
the duration, the time spent in the sauna,
when I said 50% reduction
in cardiovascular disease related death,
what was shown was that
men that were in the sauna
for only 11 minutes,
even if they used it four
to seven times a week,
that reduction was only
like 8% instead of 50.
It had to be greater than 19 minutes,
so like 20 minutes is the sweet spot,
at about 174 degrees Fahrenheit.
And most of the saunas
in Finland, by the way,
they're humid, so they put hot water,
they put water on hot
rocks to create steam,
so it's usually between 10 to 20% humidity
in the Finnish sauna.
So those studies were, I
would say, most of the time,
you're going to find that their
humidity is also elevated.
But, to me, the
dose-dependent nature of it
and the duration,
to me, that's very strong
data that this is more causal
than some corollary thing.
Because that's always the problem
with observational
studies, including these,
which they corrected for
a whole host of factors,
like cholesterol,
exercise, just everything,
everything under the sun,
they corrected for those.
And, on top of that,
you have the dose-dependent
nature of the duration,
the time spent in the
sauna, and the frequency.
So, to me, it's like,
something's going on here.
- Yeah.
- Plus there's been studies,
intervention studies,
where it's comparing
directly, head-to-head
moderate-intensity aerobic
exercise on a stationary cycle
to 20 minutes in a sauna.
Physiologically the same things happen,
so heart rate elevates while
you're doing the activity,
blood pressure increases while
you're doing the activity,
but then, after, heart rate decreases,
resting heart rate
decreases below baseline,
blood pressure is improved, so
it decreases below baseline.
This is happening the same
in moderate-intensity
cycling versus sauna.
So, again, the sauna, this heat stress,
there's something about
it that really mimics
this moderate-intensity aerobic exercise,
which is really great for
people that can't go for a run,
that can't even get on a
bike, so disabled people.
Granted, there are some safety concerns.
They're pretty mild, but they do exist.
So people that had a recent heart attack
or have some rare kind of
heart disease or problem.
Drinking alcohol, never do that.
Elderly people prone
to low blood pressure.
Always talk to a physician
before doing the sauna.
It is stressful.
- Pregnant.
- Pregnant women, yeah.
I definitely avoided
saunas when I was pregnant.
I think it's very relevant
for disabled people
and also people that are sedentary
or been sedentary most of their life.
Like, my mother, I've been
able to get her in the sauna
because she's not.
I did get her on the Peloton once,
but it's really much easier.
She feels like it's a spa treatment,
and she can listen to her music in there.
Like, I care about her health,
but she's mostly been a sedentary person.
And so I find it much
easier to convince her
to get in the sauna
than to get on Peloton.
Ideally, you do both.
The question would be,
well, I exercise, I run,
I do my high-intensity interval training.
Why do I need to get in the sauna?
And the reality is,
and so I published all this in a review
in the Experimental Dermatology
last year, I guess, late last year.
Basically, cardiorespiratory fitness,
which is a marker of,
it's a marker of health.
Cardiorespiratory fitness is improved
in people that do exercise and sauna
compared to exercise alone or sauna alone.
So, for those healthy,
fit people out there
already exercising,
there's a synergistic effect
by also adding a sauna into that routine.
And, to me, that's great.
And there's so many beneficial things
happening with the heat stress.
In addition to mimicking aerobic exercise,
there's the heat shock proteins
that we talked about earlier.
And those, it kind of brings me back
to my early days of science
when I at the Salk Institute
for Biological Studies
doing research on little
nematode worms that we
or someone else injected amyloid beta 42,
the peptide, the 42-amino
acid peptide that is involved
in amyloid plaques found in the brain
correlating with Alzheimer's disease
and other brain disorders.
We injected those into the
muscle tissue of worms.
And, basically, these worms
become paralyzed with age
because the aggregated proteins,
these proteins aggregate.
Well, heat shock proteins,
one of the main things they
do is they basically make sure
the proteins inside of your cells
maintain their proper
three-dimensional structure
and are folded right, and so they don't,
they're not prone to aggregating
and forming these plaques
in your arteries and also in the brain.
Back to my worm studies I was doing,
I would elevate heat shock
proteins in these worms,
and it would totally correct the problem,
where they would no
longer become paralyzed.
They'd move around like they were young.
So, many animal studies have been done
looking at Alzheimer's disease,
a human-like Alzheimer's
disease in a rodent,
and heat shock proteins
protecting from it.
Heat shock proteins are
robustly activated in humans.
This has been shown to,
even 50% higher over baseline
levels after just 30 minutes
at 163 degrees Fahrenheit in the sauna.
And they stay activated,
at least, in rodents,
for 48 hours, at least.
So having these heat
shock proteins around,
making sure they're properly
taking care of our proteins
so they're not aggregating in
our brains and in our plaques,
could be another potential
way that sauna's protecting
from Alzheimer's disease and
other cardiovascular health
as well as longevity.
There's people that have SNPs
in heat shock protein factor 70
that, if they have one of them,
so they got one from their parents
where they have more active
heat shock protein 70,
they live on average one year longer
than people that don't have that SNP.
And if they have two versions,
if they got one from their
mom and one from their dad,
they live on average two years longer
than people that don't have that SNP.
- [Andrew] Wow.
- So it's also been associated
with human longevity as
well as in lower organisms.
So you can heat shock a worm or a fly
and they live 15% longer.
This is work done by Gordon
Lithgow at the Buck Institute
years and years ago.
So, anyways,
I guess what I was getting at
was the heat shock proteins
are part of that stress response pathway
that we talked about earlier.
They're also activated by cold as well.
Cold shock does activate
heat shock proteins.
Not as robust. Sulforaphane
activates them.
Again, it's one of the reasons
I think we should get all of these things
because they are more robust inputs.
The input activating
mechanisms are more robust
for different ones.
So there is crosstalk.
I guess it'd be more accurate
to say there's overlap.
But it's also like,
you want to get the most
robust from all of them, right?
I do, so that's why I want
to do the sauna and exercise
and eat my broccoli
sprouts and all that stuff.
- It's super interesting.
A couple of questions came up for me.
One is, you mentioned these SNPs,
these nucleotide repeats,
basically genes that
some people have more of
or less of than others
that can predict longevity in some sense.
Is that the FOXO3 pathway?
- That's one that can.
Yeah, I mean, FOXO3 is, in fact,
if you go back to the worm
studies I was talking about,
that was one of the first things
when you see it with your own eyes.
You can take these worms that,
you basically decrease their
insulin signaling pathway
and their IGF-1.
Worms have what are
called homologous genes,
so they have a lot of
similarities to humans.
They have an insulin-like receptor,
they have an IGF-1-like receptor,
and they make something
like FOXO3, which we have.
And, basically, if you decrease
that insulin signaling pathway,
then FOXO3 is always
active in those worms,
and they live like 100% longer.
And not only do they live longer,
they are like a very young worm.
I mean, you look at this
thing and you're like,
"This looks like the worm that
was just born like hours ago.
"What's going on? This thing's
at the end of its life."
Now, as a side note,
the thing that always got me on this was,
by the way, this was
discovered by Cynthia Kenyon.
This was back in the '90s.
Honestly, I'm not sure that anything
has been as exciting in
the worm world since then,
but I thought it was a really big finding.
The only caveat there
is that the worms go through this dauer.
It's called a dauer
stage when this happens,
when you decrease their
insulin signaling and stuff,
and they go into this
like metabolic stasis.
They're not eating as much or moving.
And so it's like, okay,
well they live 100% longer,
but they go into this
weird state, you know?
- I know people like this,
some in the longevity community.
They know who they are.
But they'll get the last
laugh 'cause I'll be dead,
well fed but dead, and
they'll still be going.
So, in terms of the many data on sauna,
and I also just want to
acknowledge these Finnish groups
that did this work.
It's really pioneering, right?
When you think 20 years ago,
long before social media or any of this,
and they're out there,
up there, I should say,
measuring cortisol and growth
hormone and all this stuff
in people getting in and out of sauna.
Very, very interesting.
So 20 minutes seems like the threshold
at 170 degrees Fahrenheit.
More times per week seems
to be better than fewer
in terms of all-cause
mortality, cardiovascular risk
according to what I just learned from you.
- Four would be a good, I
think, minimum effective dose.
- Four times a week, and you
combine it with the cold.
I've also seen a protocol, where,
it's a very extreme protocol,
I don't recommend this to
people right off the bat,
where they had human subjects
get into the sauna for 30
minutes, get out for five,
30 minutes, get out for five, 30 minutes,
for a total of two hours of exposure,
but that was what led to these
massive 16-fold increases
in growth hormone.
And they had to do it very seldom.
So it sounds like these
protocols you're describing,
20 minutes done four times per week,
are far more reasonable
for most people to access.
But I know people are
probably desperate to know,
what if they don't have a sauna?
A sauna is kind of a unique item,
so I have a couple questions.
Can people use hot baths?
With the appropriate warning, of course.
Without getting into description
of the mechanics and
the underlying biology,
it's pretty obvious that the testes,
if they get too warm, you'll kill sperm.
That's the reason why
the testes are housed
in a structure called the
scrotum that can move around,
so just to be, you know,
we are biologists, just
talking about realities here.
So, if you're trying to conceive children
or keep your sperm healthy,
guys should probably stay
out of warm, hot baths.
- For at least six months.
That's been shown.
- [Andrew] Six months.
- So sperm motility goes down
and sperm production goes down,
but that is completely corrected
if they stay out of the
sauna for six months.
So through six months
later, it's back to normal.
- Great, that's a very
useful information, I'm sure,
to a number of people out there.
So, if people don't
have access to a sauna,
and we get this about cold too.
People always say, "What
about cold showers?"
And I always say, well,
the studies have mainly
been done on immersion
'cause it's hard to keep things
controlled in cold showers.
It just doesn't make for
a very good experiment
'cause you get a bigger person,
less of them is under the shower,
and so it doesn't make
for a good experiment.
So it's not as good as immersion,
but, with heat, I could
imagine that a hot bath
would work almost as well.
- Yeah, so there's been
some studies looking at,
for example, activation
of heat shock proteins,
also brain-derived
neurotrophic factor increases
with heat stress.
And so the hot bath at around
104 degrees Fahrenheit,
which is typically what studies
will use for temperature,
which is actually cooler than what I.
I crank my bath hot. It's so hot.
- But you're very heat adapted.
- I'm very heat adapted, yeah.
And it's 20 minutes
from the shoulders down,
and that is a very robust
activation in heat shock proteins
and in brain-derived neurotrophic factor.
And then, heat shock
proteins are also protecting
against muscle atrophy,
so that's also having to do
with the protein structure
and the muscle tissue as well.
And this has been studies in animal data
as well as some recent human data as well.
It was local hyperthermia
or local heat treatment,
but essentially it
showed that it protected.
There was a study where they
were looking at muscle disuse,
and it was something like
the local heat treatment
prevented almost 40% of the
muscle atrophy from disuse.
And it's funny 'cause
I used to use the sauna
when I was injured and stuff.
I would go in the sauna.
Because I didn't know at the time
'cause I was a graduate student,
but I knew just from experiments
that I'm not losing as much muscle.
I feel better.
At the time, I was reading
all about the growth hormone
and stuff back then.
And I knew about heat shock proteins,
so I kind of knew, but that
data wasn't around yet,
and so now we have the data.
And I've always felt like
I wasn't losing my muscle,
like I should've been,
when I was doing the sauna.
And I was doing it
literally seven days a week.
It was hardcore.
- This is also during graduate school?
- Yeah, now, I'm doing the sauna,
like a bare minimum, I do
three, but I try to do four.
It all depends on my schedule.
I also like to do long runs.
Long being like three miles,
not like campaigns, which are long.
But I really, for me,
and we were talking about
this earlier off camera
that the runs, for me, are for my brain.
And I'd get this mind-wandering effect,
where I daydream and I think about things.
I work through problems.
I get creative. I come up with ideas.
And this is all happening on the runs.
And so I miss my runs if I don't do 'em,
and I miss it because of the
brain effects I get from it.
And when I exercise, it's funny,
because I'm a female, and you'd
think that I'd be exercising
to stay fit and in shape
and care about my figure,
but, when I exercise,
literally what I'm
thinking about is my brain.
And I'm like, "This is the
best longevity drug there is.
"This is it right here, Rhonda.
"You're always wondering.
You're always wanting to know.
"You're wanting to do the best."
If you don't exercise, you're
missing that essential dose.
And so that, for me, is the motivation,
the dopamine seeking
thing I'm looking for.
Admittedly, I do not do
enough strength training.
And I have to do it. Have
to, have to, have to.
I'm so after the endurance and the HIT,
and I really need to add that in.
Because muscle mass is
also extremely important
for aging as well, you know?
So that's my fault.
- Well, the brain effects
are really interesting.
I also run.
I try and get one longer run
per week and a few other runs,
and I do it without a phone.
I don't listen to podcasts.
I occasionally will listen to music,
but I really try not to.
I also find that my mind solves problems.
I feel like it washes out
the cobwebs, so to speak.
Some of the most brilliant
and prolific neuroscientists that I know
who've had very long careers.
Eric Kandel, Nobel Prize
winner at Columbia,
comes to mind for all his work on memory,
used to swim a mile a day,
and now I think swims half a mile a day,
but he's in his late 90s
and he's still sharp,
which is incredible.
And his lab has done some work showing
that any load-bearing exercise
repeated, so endurance work,
unlike the Peloton or cycling,
that's really load-bearing,
although you're cycling really
hard with the resistance,
but causes the release of
osteocalcin from the bones,
which acts in an endocrine
way, sort of like a hormone,
can actually travel to the hippocampus
and, at least in these animal studies,
induce the proliferation of
neurons, growth of synapses,
BDNF, a number of downstream things,
which kind of makes sense,
if we were to put a just so
evolutionary story on this.
A body that's active
can signal to the brain
that the body still needs cognition.
An inactive body, in some ways,
is depriving the brain of any signal
about what the body is doing, right?
Obviously, I'm making
this up as conjecture,
but we know in various ocean animals
that they'll swim around for
some period of their life,
and then they'll have
a completely stationary
portion of their life,
and basically, the brain degenerates.
You don't need much of a nervous system
if you're not moving.
So I think there's really something there,
and also just letting
the ideas and mind drift.
I love that you,
and I appreciate that you
shared your protocols,
because I think, right now,
we're in an interesting time
in public health information history,
where people are just
kind of getting bombarded
with cold is good, heat is gold.
Cold is good. Heat is good.
Excuse me, I misspoke.
There are all these micronutrients,
and, of course, macronutrients
are important too.
Today, you've really enriched
us with the description
of the underlying mechanisms
and the logic behind them,
but also sharing what you
do is really informative
because I think people
need a jumping-off place,
and obviously they need
to start someplace,
and getting heat adapted,
et cetera, takes time.
But I really appreciate
that you're willing to
share your protocols
and that you do the things that you teach
and educate people about.
As a final question,
because I have to ask,
red light sauna or no red light sauna?
I've been a little bit
vocal about my feelings
that none of the red light
saunas I've ever been in
got hot enough, and it was frustrating,
so I feel like it's
neither here nor there.
However, I do acknowledge that red light
and low-level light therapies
are now known to do a number
of interesting things.
There was a Nobel Prize in 1908
for phototherapy for lupus,
so it's not like a new thing
the idea that light could do things
positive for our biology.
But, do you have a red
light in your sauna?
Do you think it's useful?
And I mention this because
this is the number one question
I get about sauna,
red light or no red light,
or some intermediate answer.
- So I don't have an infrared sauna,
but I have a sauna that has lights.
It makes red light, but I
don't think it's the red light
that you're talking about.
- Okay.
- It's not activating it
at a specific wavelength,
which is...
- It's usually, so the range
that seems to be helpful,
and, I confess, I use a red
light panel for other things,
is 670 nanometer
out to about 720 nanometer,
so it looks like red and very dim lights,
dim red and bright red.
And the idea is that red light can travel,
the photon and energy is
such that it can travel down
through the deep layers
of the dermis of the skin.
- I don't have a red light in my sauna.
I don't know if it's essential
or not. I don't think so.
Based on all the studies
I've talked about, I think,
the potential effect on
mitochondria is interesting.
I do think there's a lack
of really good, solid evidence in humans,
but that might only be because
it's just not studied enough.
And that's usually the case, so perhaps.
There's the Joovv, right? The Joovv.
They have those red
light panels and stuff.
- Joovv and KOZE are the two ones I know,
K-O-Z-E and Joovv.
As far as I know,
I'm probably going to insult
both companies at the same time,
but I'd rather insult
them both at the same time
than just compliment one or insult one.
Both of them seem excellent
for getting the appropriate
wavelengths of red light.
And I do not have a relationship
to either of those.
- Yeah.
Well, I personally think that
the sauna in and of itself,
it's about the heat stress.
And typically the question I get is,
infrared sauna or regular sauna?
And there are some differences as well.
Infrared saunas.
Maybe the infrared saunas are the ones
that have the red light
that you're talking about.
Infrared saunas only get up to
around 140 degrees Fahrenheit.
So, as I mentioned,
the studies were about
174 degrees Fahrenheit.
And so you really have to stay
in a longer period of time.
However, there have been some
studies coming out of Japan.
They use infrared sauna.
They have this whole protocol.
It's called Waon therapy.
They get people in infrared saunas,
and then they wrap 'em in a towel,
and they stay warm for X amount.
So the whole protocol ends
up being like an hour long,
but, again, it's 140 degrees Fahrenheit,
so it's an infrared sauna,
and it's been shown to
improve a variety of,
like, coronary heart
disease and conditions,
heart-related conditions.
There have been some improvements.
So, obviously, there's
evidence that infrared saunas
can be beneficial for
cardiovascular health.
I've used infrared saunas
many times at my in-laws.
They have an infrared sauna.
And I have to crank that
thing up for a while
until it's maxed,
and then I have to sit in
there for an hour at least.
I do sweat a lot,
and that's another thing
we didn't talk about.
You do sweat some heavy metals.
And some heavy metals are
excreted predominantly
through sweat and others through urine.
So, for example, cadmium,
there's like a 125-fold increase
in cadmium excretion from sweat
when you get in the sauna.
Also, lead is something like
17-fold excretions higher.
Another one is aluminum.
It's about fourfold higher.
So infrared, you do sweat a lot too,
and that's because the main difference
is that you're heating your body up
through thermal radiation
versus the ambient air.
A standard sauna is a heater,
and the heater's heating up the air,
and that's how you're heating yourself up.
So it is a little bit of
a different mechanism.
I prefer regular saunas.
Most of the data out there is
from the heat stress itself.
Like, your heart rate's
elevating when you're in there.
You're feeling hot. You're
getting that cardiovascular.
That's what you're feeling
when you're in a hot sauna.
And that, for me, takes a really long time
in the infrared sauna,
like at the very end.
But I do think there are
some benefits from infrared.
And they are more affordable.
They're less of a fire hazard.
But, again, hot baths are, I think,
a good alternative
modality for heat stress
compared to like a regular sauna.
- Great, that's a really helpful answer.
Like I said, I use the red
light, but not in the sauna.
And thank you for reminding us
of that 174 degree Fahrenheit threshold
that is mainly used in all these studies.
We covered a lot of territory,
but I just want to thank you again.
It was extremely thorough
and extremely informative.
My notes always look a little
bit like they were drawn out
by a macaque monkey who has no knowledge
of the English language,
but I can decipher this
to tell you that there
are at least 10 additions
to my current protocols
that I'm going to add.
And I'll have lots of questions,
so I apologize in advance for that.
But, on behalf of the listeners
and just directly from me,
thank you so much for your time.
I learned a ton.
- My pleasure. Thanks for having me on.
It was a really awesome
conversation, so I enjoyed it a lot.
- Let's do it again.
- Totally.
- [Andrew] Great.
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