Huberman Lab - Dr. Rhonda Patrick: Micronutrients for Health & Longevity

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Welcome to the Huberman Lab Podcast,

where we discuss science

and science-based tools for everyday life.

I’m Andrew Huberman,

and I’m a professor of neurobiology and ophthalmology

at Stanford School of Medicine.

Today, 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, Found My Fitness,

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 am 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 discuss 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 is the website

where you can get access to that podcast.

It’s also on Apple and Spotify

and YouTube as Found My Fitness.

Dr. Patrick also has a terrific newsletter

that I recommend signing up for.

It’s slash 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 Momentus Supplements.

Our motivation for partnering with Momentus

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 slash Huberman,

you will see those formulations.

I should mention that we are going to add more formulations

in the months to come,

and you will 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 derive

the maximum benefit from those supplements.

And many of you will probably also be pleased to learn

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So once again, if you go to slash Huberman,

you will find what we firmly believe

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and the best protocols for taking those supplements

along with the ideal behavioral protocols

to combine with those supplement formulations.

Before we begin, I’d like to emphasize that this podcast

is separate from my teaching and research roles at Stanford.

It is however, part of my desire and effort

to bring zero cost to consumer information about science

and science related tools to the general public.

In keeping with that theme,

I’d like to thank the sponsors of today’s podcast.

Our first sponsor is Athletic Greens.

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The reason I started taking Athletic Greens

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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,

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If you’d like to try Athletic Greens,

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I’m pleased to announce that the Huberman Lab Podcast

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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.

That’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, so.

Thank you.

It’s absolutely true.

If anyone does their research,

they will realize that the statement I just made

is absolutely true,

and there isn’t even a close second.

You know, 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 a 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.

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.

And 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 bound in plants.

These are things like polyphenols or flavanols.

Humans were,

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.

So 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 is 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, right?

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 these 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 apply,

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 know, 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.

Like 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 know, you’re gonna more robustly activate

heat shock proteins from heat versus cold,

but there is some overlap.

So I think that sort of forms a foundation there.

Yeah, that’s very helpful.

And you know, it brings to mind

in the context of the nervous system,

I always tell people, you know,

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.

And 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 than 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 scenarios 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, I think that it’s almost impossible.

I mean, you’d have to eat nothing

but the same plant all day, every day in large.

I mean, the bioavailability of these compounds in the plants

they’re attached to a food matrix.

You know, it’s not like taking it

in a supplement form as well.

It’s such that like, 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 like, 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.

And they get, yeah.

And they’re like iodine deficient on top of that.

So, you know, I do think there’s there,

you can of course make, I mean, there are types of plants

that are toxic in small quantities, right?

I mean, that-


Hemlock, exactly.

We’ll kill you.

Folks, don’t play this game with hemlock.

But you’re not gonna get poisoned from eating,

you know, 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.

Plants, meat, and starches,

I’m one of those rare omnivores out there now.

I feel like it’s rare to be an omnivore.

But I think once you step out of the social medias,

as you said, the blogosphere, most people,

I would say 99% of people on the planet

are probably omnivores.


And someone will probably correct me,

but I doubt the number falls below 98.

I think if you look at data,

you know, and when we have carnivore data,

like I can’t wait to see it,

but like right now it’s a lot of,

okay, well, this is a lot of anecdotal evidence.

And there’s, you know, there’s a good,

there’s a lot of good starts with anecdotes,

but like 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.

You know, they may be beneficial short-term.

They may, you know, be beneficial

for reasons of elimination of other things,

like who knows, right?

Lots of possibilities.

But I do think with respect to plants,

you know, 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

that are related to like 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.

So these are genetically,

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 like colon cancer

and increased cancer risk.

But if they eat a lot of broccoli

and cruciferous vegetables, it negates that risk

because they’re getting sulforaphane,

which activates a lot of the glutathione transferase

and synthase genes.

So glutathione is a major antioxidant in our brain,

in our vascular system, in our body, basically.

So, you know, there’s evidence that eating things

like compounds that are like sulforaphane or broccoli

or broccoli sprouts, which have like 100,

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.

That is amazing.

In plasma, yeah.

Sorry to interrupt.

I just want to make sure when,

so broccoli sprouts are different than broccoli.

And you just told us that they have much,

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 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 converts it 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 because 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, you know,

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,

like it’s just a little spice, you know?

And if you don’t taste that, it’s expired.

Like it should have a little kick.

And because I know people will want to know

how often and how much, you know,

are you eating this every day or most days of the week?

Well, I had shifted to supplementation with sulforaphane.

I’ve admitted, I’m admitting right now

that I’ve been terrible about it the past,

like, 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, you know,

has done a lot of research on Moringa as well,

that it’s like a cousin and it activates the Nrf2 pathway

similarly to sulforaphane.

And so I’ve been buying this Cooly Cooly Moringa powder.

I don’t have any affiliation with them.

Cooly Cooly is a brand.

Cooly Cooly is the brand.

That you have no affiliation to.

I have no affiliation,

but Jed Fahey like has researched it,

like that specific brand.

And so it’s like legit, you know, it’s like 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?

So 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, let’s take the David Sinclarian approach.

What do you, where he’ll talk about what he does

as a way to deal with this.

And of course, everybody’s different

and should in all seriousness,

should anytime you add or delete something

from your consumption,

should consult some trusted healthcare professional,

trusted by you.

What, do you recall the dosages?

I do a big heaping tablespoon.

So Moringa, Kuli Kuli Moringa, it sounds like a song.

It’s with a K, I know.

But, you know, for people also listening,

it’s like, well, why would I do that?

You know, I mentioned the glutathione in the brain.

I mentioned it in plasma.

It’s been shown to lower DNA damage in people

and white blood cells.

It’s also been shown,

there’s been several different studies in China.

You know, in China, there’s a lot of air pollution.

And I mentioned that, you know,

it’s a very powerful activator, Nrf2.

And I know you’re familiar with Nrf2,

but Nrf2 is like, it’s your transcription factor.

That is, it is binding to a little specific sequence

in a variety of different genes.

And it’s like turning them on,

or in some cases, turning them off.

It’s regulating what’s being activated

or what’s not being activated or 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,

like, please try to quit.

Yeah, you’re mutating your DNA.

I mean, yeah.

Just 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 like 60% benzene

and acrolein.

I mean, that’s something that we get in cooked food.

It’s coming out in their urine.

Coming out in their urine.


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,

because I’ve been deep diving on supplements

since I was in my teens.

This is fascinating.

And it brings me back to this question that we had before.

And I appreciate that you 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.


And that our bodies,

we’re supposed to be getting that stress

to have those pathways activated.

Like it is like, you know, right?

I mean, this is conserved among different animals.

Like 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.


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, you know,

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 of…

We’re approaching the spring

and there’ll be a lot of graduations.

Weddings are coming up now

that the pandemic is kind of 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,

the different types of intermittent challenge.

And we are rewarded with particular compounds

that are reparative, both for the challenge,

but then it make us stronger.

It is, 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?


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.

Like 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 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 or hockey players or 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 you 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,

I mean, it’s terrible, but it’s also,

it’s so interesting because it’s also

like literal real-time brain aging.

Like, you know, like it’s,

you’re able to like 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, you know?

And so sulforaphane, I personally think,

and I do think there’s been some animal research with TBI,

I mean, and sulforaphane,

mostly preconditioning rather than treatment.

So again, it’s like, well, I mean,

if you’re gonna, if you want a healthy lifestyle thing

and you’re a construction worker

or you’re fill in the blank, that’s, you know, gonna,

I mean, anyone that drives a car,

I mean, you’re at risk to some degree, right?

Or bicycle.

Bicycle, yeah.

Around Stanford, we have, you know,

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’ve lost,

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 is, it’s a risky sport by any stretch.

So in taking things like Moringa

or in 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, right?

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, you know,

just even in plasma cells, I mean, I think it’s pretty,

NRF2 is pretty ubiquitously expressed.

Liver, so there’s, I mean, there’s so many animal studies

that I’ve looked at all those things.

I try to kind of gravitate towards human ones

because it’s a little, a lot more relevant,

but I think, you know, overall, like I mentioned,

you know, DNA damage lower, I think it was like 24,

24 or 34% lower in human blood cells

after broccoli sprout powder supplementation.

And I made a video on this like years ago, 2016, maybe,

and I think I have like 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, you know, it’s also been shown

in randomized controlled trials

to help treat autism and autistic symptoms.

And yet again, it’s doing interesting things in the brain.

And I think it does have something to do

with the oxidative stress and 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, you know, 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

in 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 kind of top three,

your superstars of nutrients for the brain and body,

sounds like we’ve got one set.

What would you put in 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 docahexanoic acid, which is DHA.

Yeah, EPA.

I’m amazed you can pronounce two of the most difficult words

to pronounce right next to, 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.

A 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 in marine sources.

So fish, so sardines, cod, this sort of thing.

But what about krill?

I’ve seen krill oil and there was 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.

I don’t think so.

I’m not a big fan of shellfish, but I like,

you know, 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 krill,

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.

So 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.


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,

like he used to eat sardines every day.

Joe Rogan was telling me that he used to eat sardines

every day.

And then he had like really high mercury levels.

And I was really shocked because sardines are like,

you know, low in the fish, you know, group.

So the higher up you get like swordfish and sharks,

like really high mercury

because they’re eating all the other fish, right?

But I think some brands,

and if you look at like Consumer Lab,

Consumer Lab, it’s like a third party site

that I’m affiliated with,

but I use them because they do a lot of analysis

of different foods and supplements.

And so you can look at like some of their sardines

and they have a list of like 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 like a glycerol backbone

with three fatty acids and that’s attached.

And those are either DHA or the EPA.

And, 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,

it’s 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 like re-sterifying 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 like higher end

will market it like triglyceride form.

And it’s not that ethyl ester is bad.

It just means take it with food.

So one of the major prescription omega-3s out there

is both of them actually.

Lavazza, which is a mixture of DHA and EPA,

as well as Vasepa, 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.

Just to really, I just wanna 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 that you continue to do

is to move away from these very broad sweeping statements

about fat is bad.

I mean, here’s a case where we’re saying

fat is not only good,

it can be used to combat issues with fat metabolism.

And then fats are not just one thing, they’re many things.

So anyway, I just wanna 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, right?

And here we’re talking about these omega-3s.

Okay, so the triglyceride form can be taken

with or without food and there’s the prescription forms.

What’s, I can’t get, 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?

Of, yes, of the Vesipa.

I think Lavaz is 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 them prescribed

because 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 like 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.

Or the why.

I mean, we haven’t gotten there yet.

But I think that, 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.

I think four grams is, I mean, and in fact,

like, you know, Bill Harris, Dr. Bill Harris is,

he’s just one of the pioneers

on omega-3 fatty acid research.

He was on our podcast not, you know, last August.

And he was saying the reason FDA chose that

was literally just because how much

they could get people to take.

Like, it wasn’t like an upper end, like,

oh, this is not, anything above that is unsafe.

That wasn’t the case.

I mean, it was just purely like cost

and like, you know, compliance, you know?

So like 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,

Sachin 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 wholly

was actually just born out of this relationship

between these two graduate students.

You know, 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, we’d all be,

intermittent fasting would mean eating 14 hours a day.

That was a joke, not a good one,

but I 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 the stop.

So, and I think that’s important for people to hear

because so often we hear the eight hour feeding window,

you know, four grams of EPA,

you know, 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 if, I don’t think it’s necessary,

not necessarily.

I just happen to buy,

I happen to get a certain fish oil supplement

that’s like separates them.

And so, you know, like Lavazza, Lavazza is a great one

and it’s all like 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

because I’ve done the experiment of going on and off.

I take the 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, you know,

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?

Well, 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, right?

Or a thousand 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, right?

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.

It makes perfect sense.

Right, so anyways, they measure that.

And I typically like to look for,

they give you a total oxidation number.

It’s called TOTOX, 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

because 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

with you tagged until this list is published online.

Sorry, Rhonda, but I’m gonna do it.

I know it’s very sadistic of me,

but in service to the community and myself.

And I chose five brands from each.

I tried to find one in like Europe and one in Canada.

So there was a great selection of US and other.

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 SSRI serotonin,

selective serotonin reuptake inhibitors

and 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.

And so maybe you could tell us,

what are some things that getting 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 like within that paper,

like the doing background research,

and this was a review article, by the way,

I was just connecting dots.

No, I’m gonna grab it.

I confess I don’t know the paper,

but I love quality reviews

because the references therein are so useful.

Well, there’s a huge role for inflammation,

the cause of inflammation and depression.

And I think we did a short animated video on this as well,

like years ago back when I was publishing that work

where people are injected with lipopolysaccharide.

I mean, 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 like 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 a 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?

The depressive symptoms versus the placebo.

So the placebo was saline control.

So this was a placebo control

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 hypothalamic areas

and cranks up body temperature

because basically it’s a signal that the body is infected.

Right, 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.

Is that okay?

Yes, yeah, yeah.

And to kind of, boy, we got a lot of things to hit back on

because one of your original questions

was krill oil versus fish oil.

And DHA specifically is in phospholipid form,

it’s more bioavailable.

So our bodies, 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, not plasma cells,

in your plasma with krill oil.

However, krill oil supplements are so low dose.

Like, I mean, good luck getting two grams

of omega-3 from krill oil.

And also krill oil supplements are notoriously like 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’s just like, it just smells rancid.

So, but the thing is,

and I also published a paper on this back in 2019 or,

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 I kind of-

With an Alzheimer’s susceptibility.

Right, so like 25% of the population has an allele

in 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, it’s much more,

it’s less common.

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 form.

So two grams, like the magic more,

two grams or more is the magic number, I think.

So kind of back to like the why for fish oil.

And 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 gonna 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

what it’s called the omega-3 index.

So this is actually the omega-3 level in red blood cells.

So red blood cells turnover 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 of 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 know, was 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, right,

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.

They’re, you know, 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 most,

first of all, standard American diet

has 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 U.S.

And then-

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 always say it’s the only thing,

but what he showed in his data was that in,

and I think it was a Framingham study

where he looked at the omega-3 index in 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 and smokers

and their omega-3 levels.

And so he stratified it, right?

And he found smokers that had no omega-3

were like the worst of all.

I mean, it was like, it was just like worse, right?

We all know smoking is bad for us

and will take years off our life expectancy.

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.

Wow. Right?


And 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, right?

People, has there been any studies of,

specifically of vaping or people smoking marijuana

and 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,

because 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 like blunting inflammation.

They’re doing so many different,

like they affect so many different parts

of the inflammatory pathway,

which is, I think it plays a huge role

in the way we age, the way our brain ages,

the way we feel, our mood, just our joints, all that.

And so it’s amazing.

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 wanna 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

and 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 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,

because 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.


But 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

would 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.

Like 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.

And it makes sense because pregnancy,

when your estrogen just goes through the roof,

I mean, these omega-3 fatty acids

play a very important role in brain development.

So you’re, you know,

women are supposed to be converting any ALA they can

into the longer chain omega-3 fatty acids, right?

So estrogen does affect that.

But I would say plant sources,

so if you’re looking for the ALA,

plant sources would be, you know, walnuts, flax seeds.

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 do, it’s, 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, you know,

the enzymes that convert ALA into EPA and DHA,

again, it’s inefficient.

And then for people that eat fish, sardines, you said-


And you have to eat the skin, as I understand.

You don’t have to, but it’s good.

It’s rich with the oil.

Yeah, and the reason I say like,

like I think the best would be wild Alaskan salmon

versus the farm raised because the farm raised,

again, they’re feeding them, they’re feeding them corn.

They’re feeding them like grain and stuff.

And then they give them 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

in photoreceptors.

Yeah, well, you know, actually the carotenoids themselves,

so like lutein, zeaxanthin,

they’re really good at sequestering singlet oxygen,

which is damaging, right?

Yeah, as we age, because the retinal cells,

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.

I think 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, Glenn Jeffries Lab

at the University College London.

We should talk about that at some point, if not today.

I saw that study like 2020, was it?

Yeah, they have a second study.

Oh, do they?

Yeah, it’s looking real.

I mean, you know, they’re cautious.

They’re appropriately British and cautious about it.

You know, I always joke

if those studies have been done over here,

everyone would already know about it.

Glenn is a very conservative guy,

but they’ve done this stuff now in pigs and rodent models

and now also two studies in humans.

It’s looking pretty interesting.

So sardines, but also anchovies.

I mean, 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.

I had fish tanks when I was a kid.

I just don’t, 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 mutations.

So raw fish is actually higher in mercury than cooked.

Okay, well, that’s good.

Now, I don’t really like sushi that much anyway.

You’re giving me great reasons to not eat fish,

but except I should eat these other fish sources

or supplement more heavily.

That’s the message I’m getting.

I eat sardines, like every day,

my like first meal almost is like a can of sardines

and an avocado with like-

Avocado is good.

Yeah, with a little bit of lemon

and then some little hot sauce, like, you know.

Does avocado have omega-3s?

Avocado is very good in monounsaturated fat.

It’s not really high in polyunsaturated fat.

Omega-3 really, I mean, it’s either the DHA and EPA

that’s in the marine sources, fish,

or it’s the plant ALA source,

which is like the flax seed 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, you know, I love the taste of steak.

The point here is that if you don’t,

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%, right?

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 that, 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 can somebody measure,

where and how can somebody measure their omega-3 index?

Which again, just to remind people is the,

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.

I misunderstood.

So most people are measuring,

like 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.


The phospholipids, it’s in a phospholipid, right?

So your phospholipids are carrying things.

These are lipoproteins.

They’re carrying things like omega-3 intraglycerides

and stuff and shuttling them around.

So 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

is called OmegaQuant,

and they measure the omega-3 index.

They have a variety of different index tests.

You can do like 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 the money to funnel back

into doing lipid research.

He’s out there doing all sorts of interesting studies

on omega-3s, 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 it just, we need to like,

as scientists, we need to come together

and like make some progress.

I mean, 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 like 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

and 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.

You mentioned you, so you basically,

when now 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.

To do the 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 hope, 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?

I mean, 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.

So these, from the metabolites of like DHA, for example,

resolvins play a role in resolving inflammation.

Like you want your inflammatory response to be activated

when it’s supposed to be,

but you wanna 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.

And so there’s just, and there’s,

I think there’s just so many different ways and inputs.

And so when we talk about inflammation,

honestly, it’s a big general term,

but you’re talking about,

when you’re talking about serotonin release

at the level of neurons,

we know that these inflammatory molecules

cross the blood-brain barrier.

And I just mentioned ago about injecting people

with lipopolysaccharide and causing depressive symptoms.

You know, it’s known that 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,


So 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,

you know, 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

because I’m not a neuroscientist.

No, but it makes perfect sense.

I mean, 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.

And 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 if getting that right,

you wouldn’t want it as rigid as concrete,

but you wouldn’t want it as soft as,

I need to come up with something here.

What’s that gooey stuff that kids play with?

It’s like that goo.

Anyway, it’s disgusting and it’s too soft

to be a membrane for a neuron.

That’s what we know.

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.

It’s a balance.

And in mentioning DHA, I’m just gonna,

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-

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.

So, 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 gonna get phospholipid form anyway,

because your body’s gonna 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.

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 put the fish egg on the thing.

That’s probably not good.

Although it’s good enough for the fish, apparently.


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 in 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.

And 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, right?

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 like six times as long

as someone with none of that natural sunscreen.

So I think the take-home there is,

you know, a lot of people with a 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 there’s,

you tend to see darker skin

because it’s protection from the burning rays of the sun.

And adaptation.

They are in the sun more.

Right, yeah.

And they’re getting more vitamin D,

but people that maybe moved to the United States,

to like Minnesota or in a place where, you know,

UVB radiation isn’t, you know,

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, you know,

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-


So this is everyone.

And so I think that insufficient levels

defined as less than 30 nanograms per milliliter.

And that’s sort of defined by the Endocrine Society,

looking at a lot of different aggregate studies,

and 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, right?

But also skin cancer is, you know,

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,

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.

Like imagine 70% of the population

having insufficient testosterone, right?

It’s a steroid hormone.

Which we might be headed there, but probably not.

No, I think that it’s 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, you know, variant, blah, blah, blah.

It doesn’t sound like a hormone.

I also, I’m glad that you’re mentioning skin

as the major kind of 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

where this took place over in Israel

where they had people get outside for 20 to 30 minutes

a day, three times a week,

exposing a culturally acceptable yet, you know,

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.

They did a bunch of, 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 a production of a hormone is really interesting

and makes total sense.

So when vitamin D gets into cells

and it’s binding to these VDREs,

what sorts of things are they triggering?

So like for testosterone,

we know it’s gonna trigger protein synthesis,

muscle growth, tendon strength, et cetera.

With estrogen, it’s gonna be keep your neurons going,

your joints feeling good.

I always remind people that, by the way,

because guys are 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.

And this was, I say more than

because when I was looking at this data really in depth

back in 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

and tryptophan hydroxylase 2,

so for people listening, tryptophan hydroxylase

is an enzyme that converts tryptophan into serotonin.

So tryptophan is what we,

an amino acid that we get from our food.

You convert serotonin,

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 hypothesize

that it might actually be repressed by vitamin D

because it has a sequence.

The sequence itself, this 12 nucleotide sequence,

it can determine to some degree

whether it’s gonna be activated or turned off.

And so like I was able to kind of look at that

and think, oh, maybe this and that.

And so since then there’ve been some groups

that have confirmed more with in vivo

and or in vitro studies,

because mine was all in silico and all that stuff.

But anyways, so serotonin, a really important one.

But most people, I mean,

this is regulating our immune cell, immune system.

It’s regulating our blood pressure,

all that water retention.

I mean, bone, of course, homeostasis, 5%, more than 5%.

I mean, I can’t tell you like so much.

I mean, and with 70% of the US population deficient,

I’m beginning to think that this could be the linchpin

in a number of really important issues.

So supplementing vitamin D3 is what I normally,

here is the, I do, I take,

I think I ended 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

as 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 is, to me, is striking because they eat quite well,

they’re a healthy weight, et cetera.

But it, 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 mean, 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.

Their vitamin D2 would be a plant source.

You often find it fortified in like foods like milk,

usually D2.

Does anyone still drink milk besides kids?

Out here it’s like, you can’t find cow’s milk.

I mean, all the lattes that you’re getting.

Soy milk, what’s the other one?

They’re fortified in those as well.

Oh, they are, okay.

They are, yeah, they’re fortified in-

I have a hard time finding cow’s 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.

Like, you know, like you think about cod liver oil, right?

It’s like, it has vitamin D, but it’s not,

you’re not gonna correct a deficiency

with eating fish for your vitamin D.

Like you’re either gonna 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 doing that,

converting vitamin D, making vitamin D3 in your skin.

Well, that’s probably what was going on here

because this person is getting up in their-

There’s a lot of single nucleotide polymorphisms.

We talked about ApoE4 previously,

but there’s a variety of genes that people have,

very common actually.

In fact, I’ve had many people that have had to do,

done that exact same thing.

So measuring your vitamin D levels

before and after supplementation

is the only way you’re gonna figure that out, right?

Very important.

If you don’t measure it, like you don’t know,

like, you 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 people,

scientists will look at common SNPs,

people that have these common variations of a gene

that’s a little more than 1% of the population.

So it’s not a random mutation.

It’s actually found in a sizable 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 factors.

So vitamin D and SNPs

that basically make the conversion of vitamin,

either vitamin D precursor into D3

or in D3 into 25-hydroxy vitamin D

or into the active steroid hormone,

which is 125-hydroxy vitamin D.

And there’s a variety of different SNPs that show people.

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.

Okay, so it’s really a way

of doing a beautifully randomized controlled trial

with an observational study

because you’re not biased.

You know, 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.

But when dealing in a randomization,

it’s beautiful for that reason

where you now just randomly,

people randomly have these genes

and it’s not like there’s no health status.

Like if you have the SNP, like your friend,

like your family member was healthy and all that,

you know, 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 with, you know, 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 you’re a 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 anyway.

Your doctor will do it.

You ask him 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 wanna get to 40.

You’re gonna need at least 4,000 IUs

if you 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 really,

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 bad.

It’s like-

These steroid hormones are slow-acting.

Yeah, it’s not like a media thing, right?

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 gonna 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 in ambulatory.

So is that reasonable?

1,000 to 5,000 IUs for most people will be reasonably safe.

Again, we’re not making,

just assuming that people are gonna 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 like 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 just like a safe,

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 mil,

and I do out, I don’t put sunscreen on like all the time.

Like I do put it on my face and I wear a hat,

but like some of my skin is being exposed.

So I do make it, you know, 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,

or, you know, are you all covered up out in the sun?

Well, that might be great

for setting your circadian rhythm

by way of a light to through the eyes,

because that’s the primary mechanism for that.

But it seems to me that the more of your body surface

that you can safely and appropriately,

please folks, appropriately exposed to the sun,

the more vitamin D you’re going to create, right?

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, 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.

So surface area matters.

And by the way, you know,

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.

And this was a smaller study than I would like,

but it reversed their epigenetic aging by like 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.

But 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 of the complex

and you 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 sort of determine like what effects

there will be with no vitamin D, right?

Like how do you study no vitamin D?

And so what was found was that these animals,

in fact, I don’t think it was a complete knockout

or, you know, because I think it might be embryonic lethal,


Some hypomorph, 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.

I mean, they just, I mean, their lifespan shorter.

I mean, they just, 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, you know,

of course, mice lifespans are only like two,

two and a half years, but like 500 years old.

Right, it looks like it went to graduate school twice.


Actually graduate school is 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 are the data, it’s remarkable.

So I think it’s, I’m definitely gonna try

and get my omega-3 percentage up there.

I’m not gonna, you know, hinge at 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?


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.

It’s 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 I’m as, to be honest,

I’m as scared of sunscreen as I am of melanoma.

Like that some of the things in sunscreen are really spooky,

mainly the compound.

And here I’m not one of these conspirators.

I drink tap water.

Listen, folks, like people cringe with it.

I drink tap water.

I have the occasional croissant or donut.

I’m not, you know, I’m 90%, 80% of the time

I’m doing the right things the right way, I think,

although I’m now gonna 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 that the neurons you got

are basically the ones you’ve got for your entire life.

You know, there’s a reason why there’s a blood-brain barrier,

a blood ovary, and a blood testes barriers

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 like reflecting it.

It is somewhat difficult to penetrate things

all the way through the skin and get into the bloodstream.

I don’t, 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-

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 like 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, we don’t know.

I mean, like it’s completely speculation,

but there is like, I think some more and more evidence

coming out with some of those compounds.

And I can’t remember all of them off the top of my head,

but a lot of high-end ones also have,

it’s the chemical sunscreen ones, the chemical ones.

We should do, I’m proposing that we do a journal club.

A journal club, folks, is where academics get together

and read papers and 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.

Because once you’ve actually published some papers,

you realize that, you know, 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.

Because I’d love to really figure out

what’s in these compounds.

I mean, 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.

I, 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’ve 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 is about cold and heat,

which admittedly, I pulled us off that path.

So I wanna take full responsibility for that.

But before I do that,

I just wanna offer you the opportunity.

Is there anything that fit 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 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.

And it’s-

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 125-hydroxyvitamin 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.

They’re basically all of our cells need ATP to do anything.

And 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

is a insidious type,

causes an insidious type of damage daily

that you can’t look in the mirror and see.

Like when you’re deficient in vitamin C,

you’re like, my gums are falling apart.

I have scurvy, right?

But like, 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 cofactor for them.

What that means is, you know,

a cofactor means enzymes need it to function properly.

And so without that cofactor,

they’re not doing it properly.

And I like, the way I like to think about magnesium,

it’s easy because people go, what food should I eat?

Right, 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?

It’s obviously, I’m not-

And it’s high in lutein and zeaxanthin as well.

I’m a trichromat, meaning I’m not colorblind,

but I just wanna make sure it falls

under the strict category.

Because 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.

But 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,

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 get your water in.

You could drink it.

Yeah, I personally don’t worry about it.

I just don’t worry.

Well, if you don’t worry, I’m not gonna worry.

But I also like, I do supplement with magnesium.

I do take around a,

so supplementation with magnesium.

I mean, we could go on and on.

Let’s keep this short and sweet

because we’re gonna get back to the other stuff.

But it can cause GI distress at like 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 like magnesium 3-8, for example,

and it doesn’t affect the gut as much.

Magnesium citrate.

Citrate is what I take.

Yeah, it’s a pretty potent gut stimulus.

I mean, I feel like it’s a little bit harder to digest.

Well, I take 135 milligrams should be pretty good.

And citrate actually, oh boy, do we wanna go here?


I mean, it’s up to you and we don’t have to.

I 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 to.

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 acids,

citrate, malate, lactate,

but specifically malate really and lactate

are the major ones that get into the gut epithelial cells

and are energy source for the mitochondria

and the goblet cells.

So anyways, whole other topic.

That’s okay.

Yeah, 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,

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, I’ve seen the studies with the threonate.

I think like 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, right.

Yeah, I’m thinking that paired with it.

There’s some work.

Yeah, the Guosong Liu’s work on with,

so in the, this is getting kind of

into inside ball of neuroscience,

you know, that the quality of the labs matters folks.

And that’s something that’s not accessible

to people outside of fields.

And, you know, 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 thing

when you think about this being done 10, 12, 15 years ago.

And then yes, we need more human clinical data.

But I, for me, I figured that the,

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 there’s, 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.

So it, 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 I mean, you know, when you do heavy,

when you do intense exercise,

you release endotoxin from your gut.

I’m just going back to the interesting work

because the malate being the short-chain fatty acid

and, you know, Mark Shuganaga showing,

this is all in animal research, by the way.

But I mean, it was like, you know,

feeding these animals malate,

I mean, it really protected the gut, endotoxin release,

and it affected metabolic syndrome and all sorts of things.

But I think malate’s awesome.

And I always try to eat green apples.

They’re really high in malic acid.

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 Magnesium 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, you know, would love to see more clinical data as well.

But I think, you know, 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?

Right, and along those lines,

I once put out a post that said, you know,

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,

you know, randomized clinical trials, et cetera.

Then other people are just say, you know what?

I don’t even care about any of that.

Just tell me what you do.

And then other people are saying, 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.

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 if, you know, 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.

And I’m the worst combination of academic

because 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 challenges

is a really attractive one.

And I want to make sure that we credit you

with the phrase intermittent challenge.

No, credit Dr. Mark Madsen.

Okay, Dr. Mark Madsen gets credit.

And he has used that phrase.

Okay, great.

We’ll make sure.

Just like Dr. David Sinclair, I love the xenohormesis.

He was in like one of his publications

just so many years ago.

And I just love it.

It’s brilliant, a brilliant term.

So Mark Madsen gets credit for that.

Those Harvard guys are pretty smart.

You know, 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 deliberate,

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 don’t know,

pick your favorite metabolism, neuro slash 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.

And so I’m like, it’s like really hard.

So the, like, I would say like, 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.

I can’t-

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.

Yeah, and by the way,

the podcast, Nor I am sponsored by Plunge.

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 gonna go on a podcast.

I definitely do cold when I’m gonna do a podcast,

when I’m gonna 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 usually do it

before any type of public speaking

or just 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 do,

time or duration, I guess it 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, it was like two, three, four.

But who wants to do one hour?

Yeah, I’m familiar with that study.

I love, so this is 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 sort of, I relish in reading the methods.

And that paper is really interesting

because they had people sit in lawn chairs, basically,

in swimming pools for an hour.

And it wasn’t really, 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 it’s really, so the mood enhancing effects

that you report are, they’re not,

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 dream-like profile for dopamine

because most everything else, like an Adderall,

a Ritalin, a cup of coffee and a workout drink

or pre-workout drink or something

is gonna 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 where blood pressure changes,

I think, where I basically went straight

from a really hot jacuzzi.

I was in there for like 30 minutes.

I mean, I was doing heat stress.

Jacuzzi, okay.

Yeah, 104 degrees Fahrenheit.

That’s toasty.

And then I, for 30 minutes.

And then I went straight into, at the time,

it was our pool, it was in like February,

it was like winter time.

And it was 50, it was in the 50s.

It was cold.

And I was in there and I was like listening

to Simon Garfunkel.

I was like trying to stay in a long time,

get on my cold and I was trying to impress Dan

because he like goes in there for like,

he’ll stay in there for like 15 minutes.

But I started to feel really like blinky,

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 so, 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.

And it makes sense.

The sauna is causing vasodilation and the cold plunge

or cold exposure is causing vasoconstriction.

So it’s like a very, you know, just shock to my system.

And so now I wait, like I wait like a few minutes

before going in, but I do need to kind of like make it more,

the cold more routine because I talk all about the science.

I’m familiar with all the science and, you know,

the norepinephrine or noradrenaline, you know,

it’s affecting brain and mood.

And you know way more about that than I do.

I know how I feel and I know it’s a neurotransmitter

and, you know, 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 in that it’s released

from the cold in the brain.

And now in humans as well.

So in that study, that’s the, we can put a link to this.

It’s published in 2000, 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 in humans.

They did brain.

Oh, I didn’t know.

Oh, no, no, not right.

No, yeah, yeah, yeah.

Very hard to measure doping directly from the brain

unless you’re doing microdialysis.

No, it’s unfortunately that there’s,

unfortunately their skulls were intact.

Fortunately for them,

unfortunately for the research committee,

their skulls were intact.

So they couldn’t measure directly in the brain.

But obviously there’s a correlate there.

You know, it’s a very real effect.

I think that, 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 wanna be cold adapted

because that means I have more mitochondria

in my adipose tissue and perhaps even muscle,

like 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, so.

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 one,

norepinephrine is upstream of that, activating it.

So 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.

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,

the protons start leaking out of the mitochondria

and your mitochondria freak out.

So this is called uncoupling.

And they start to, it’s maximum respiration as we call it.

They try to make as much energy.

They’re like, I gotta get that proton back,

that gradient, the electrochemical gradient.

And so they just go insane.

And in this case, it’s uncoupled energy.

So the energy they’re making is actually heat, not ATP.

But heat is, 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 PGC1-alpha.

And what that protein does is it makes more mitochondria

in your adipose cells.

So per adipose cell, you’re getting more mitochondria.

It’s a beautiful way to basically make more heat

when you’re, it’s one of those things

where it’s like, your body’s going,

okay, I’m gonna 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 gonna make more heat.

And so you’re making more mitochondria

in your adipose tissue.

And this is often referred to as like the browning of fat.

And the reason for that is because if you look

under a microscope at a lipid drop,

basically a fat cell, not a lipid drop, an adipocyte,

you’ll find that it looks darker

because there’s more mitochondria in there.

So it’s referred to as browning fat.

And so I don’t wanna get into the whole beige, fat, brown.

There’s this whole, I’m sure you’ve had experts on

that talk all about that.


No, not yet.

I mean, I always think of white fat, beige fat, brown fat

and beige is kind of intermediate.

White can be converted into beige, but-

Right, and beige can take on thermogenic characteristics


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,

which is, 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 like thousands of researchers

trying to pill up brown fat and thermogenic.

Like 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 gonna like 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’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-1-alpha.

Interestingly, not that anyone else really cares,

but maybe you do, Andrew.

I’m eating this up.

So PGC-1-alpha is response to norepinephrine

and 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 it may have been men only that were exercising,

did some separate training,

and then did cold water immersion,

something like 50 degrees Fahrenheit, 15 minutes.

And PGC-1-alpha, 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.

I mean, mitochondria are essentially

either the making energy in your cell.

And we don’t make more mitochondria normally.

Like you have certain inputs,

high-intensity interval training exercise can do it.

And actually make more mitochondria.

Yes, yeah, and that’s been shown in people.

And I mean-

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.


It’s good to know.

I’m always looking for reasons

to finally do more HIIT-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.

Great place.

And he did a study where both young and older people were,

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 HIIT,

from the high-intensity interval training,

was, I mean, it was like enormous, at least 50%, I think.

So I mean, it was just like, whoa.

And so like, 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 and mitochondrial DNA

and then fizz back apart.

And that’s how they kind of stay youngish.

But like, as you age,

you keep doing that with the same pool of mitochondria

and you’re gonna get a bunch of old mitochondria

mixing old stuff together, right?

So why wouldn’t you wanna like bring up

new healthy young mitochondria into that pool, right?

So in my mind, when I hear mitochondrial biogenesis,

I’m like aging.

Like, that’s the first thing I think of.

So anyways, cold exposure does that.

Other things as well, so.

No, 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 getting,

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 gonna inspire me to change my behaviors.

I’m gonna start doing some

high-intensity interval training.

Dr. Andy Galpin was on this podcast recently,

and he told me that the subtle zone two cardio

and the weight training is great,

but that I really should be doing

some max heart rate work per week.

You know, going into max heart rate for 90 seconds

and 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 HIIT?

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,

and because you’ve been very gracious

in sharing some of what you do for supplements and food,

what about exercise?

So I, it all depends on my week, of course,

and what I’ve got going on with my son

and my work schedule.

But I typically, I do a lot of high-intensity interval

Tabatas on a stationary cycle.

I use Peloton because I just like that instructor there,

like telling me what to do

and then me competing with everyone else.

You know, so it works.

You’re revealing something about your psychology.

This is what we just learned about.

So this podcast is actually just a decoy

for psychological assessment of the guests.

No, I’m kidding.

But so now we know you’re competitive, good.

That explains a lot of how you got through graduate school

and 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 are peddling 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 have all time doing it.

So you can kind of toggle on what you want

and like you can try to compete against

the all time number.

Oh, so it’s really competitive.

Oh, yeah.


And the instructor is just there to like whip you,

like, you know, make you,

there’s a part of, the brilliance with Peloton is,

like I used to do rush, what’s called rush cycle.

And I used to go in, 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 group, 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 a pandemic,

and people talking about Peloton in my class.

And I’m like, oh, that’s ridiculous.

Why would I do that?

Like, that’s never gonna work.

I need to like be here.

And then the pandemic hit and I was like

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, you know, 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.

You’re maxing it.

And there’s a lot of resistance in the pedals?

Well, so you basically, there’s a part where you’re,

I always do resistance.

I’m like the power, I do the power for,

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 like, you feel it in your glutes.

Yeah, exactly.

And so they like break it up.

And most of the time you’ll have like those two parts.

And I love the efficiency of it.

You just, you get it done.

And people sometimes hear me go 10 minutes

or really you think you work.

I’m like, look, like you max, you do max,

you Tabata for 10 minutes.

And it’s like, 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 you think about, if I think about that,

and then I 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 I, because I’m competitive during the recovery

that they give you at the minute, at the end,

I’m pushing it max, because I want to get a number higher.

Great, so three times a week.

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 mean, I literally like down a bunch of water

and then I get in and then I like 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.

Okay, and I-

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 like small studio apartment,

the smallest apartment you could ever imagine.

And it was across the street from a YMCA,

because I was poor in graduate school.

Very poor, very poor.

I mean, so, you know-

I recall, I recall being, I lived in my lab.


Then again, I lived in my lab as a postdoc.

And as 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.

Yes, and so I used to go to the sauna

before going into the lab.

And I would, and I would, 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 your, my advisor and my own pressure,

because I’m very competitive with myself

and I put a lot of pressure on myself.

So I was having a hard time.

I mean, I was very stressed out in graduate school

and the 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.

And basically, 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,

which dynorphin is responsible for that dysphoric feeling

when you’re in the sauna and you’re hot

or when you’re running, doing exercise

and you’re like, you feel uncomfortable.

Well, I think that’s dynorphin, I’m speaking absolutely.

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 that comes in,

he was looking at the effects of like 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 down-regulated.

And so you need more and more of the drug

to feel as good as you did, right?

Well, endorphins also bind to that receptor.

And he was looking into some of the other drugs

that are like salvinorum or something, salvia, it’s called.

It binds to the 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 up-regulates 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 think, I don’t know if it has to do

with the stress response,

like when you have an emotional trigger,

like you remember things better, right?

I mean-

Absolutely, there is a clear and known explanation

for mechanism for this.

So in the sauna, I mean, you also release norepinephrine

just like you do in the cold.

There’s a lot of overlap.

You know, you’re really, I mean, it is a stressor,

but I like use it to remember things

like I’m going through something,

I wanna go through a presentation or a talk

or a podcast or whatever.

And I go in that sauna and I mean, you should try it.

Like if you haven’t already, I don’t know if you have.

I have a sauna and a cold plunge now

and I haven’t tried prepare,

I read books in the sauna in the evening.

It’s a time I insist on having my phone out of there,

mostly because I, 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 by this beautiful work

by a guy named James McGaugh.

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

inverted U-shaped function for the relationship

between adrenaline and memory.

Basically, if you’re too relaxed and not stressed enough,

you’re not gonna 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.

And then, of course, it tapers off

as you really increase adrenaline to the point

where people are starting to lose autonomic function,

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 profusion 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 profusion of blood to the brain,

plus a little bit of stress, or maybe a lot of stress

from the epinephrine, and yet it’s,

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 conditioned place context of it.

Like if we had a good experience

remembering something in the sauna once,

we tend to, 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.

The opposite is also true.

So if something good happens someplace,

I’m imagining that it’s a combination of those effects,

but I’ll start, 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 McGaugh curve.

I have to sing songs or something when I’m in there.

Distract yourself.

Oh yeah, I sing songs.

But afterward, you’re very efficient at learning.

After I am, and with respect to the sauna,

vasodilation does occur.

So there’s a lot of overlap between moderate intensity,

aerobic exercise and heat stress.

And as you can imagine, when you’re exercising,

you’re elevating your core body temperature,

you’re sweating.

And 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 that,

and there’s studies showing that sauna use

is associated with a much lower risk of dementia

and Alzheimer’s disease.

Like 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.

Oh, sorry, I didn’t mean to cut you off.

You said people who use it, I apologize,

maybe you could tell us again,

people who 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 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, like there’s a big link

between the cardiovascular system and the brain.

Obviously blood flow, a big one, right?

You know, like you need to get blood to your brain.

But cardiovascular mortality,

so mortality from cardiovascular disease

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, you know, sudden cardiac death.

It’s 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.

And 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 a lot of the, so I mentioned the temperature I do

is about, I do like 189 degrees Fahrenheit.

Typically I go in there, I’m pretty heat adapted.

And so the more you do, the more you do the sauna

or any sort of heat stress,

whether it’s a hot tub or jacuzzi, you become adapted.

You’re 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 stay in for like 30 minutes.

Like, I mean, 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

were from 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 so, and most of the saunas in Finland, by the way,

they’re humid.

So they put hot water, not hot,

they put water on hot rocks to create steam.

And 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 gonna find that their humidity is also elevated.

But to me, the dose dependent nature of it

and the duration knowing, like, you know,

to me, that’s a 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, you know, exercise, just everything,

everything under the sun.

I mean, 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.

Plus there’s been studies, intervention studies,

where it’s like, you know, comparing directly head to head,

moderate intensity aerobic exercise on a stationary cycle

to 20 minutes in a sauna.

They’re 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, like 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, you know, disabled people,

granted there are some safety concerns,

they’re pretty mild, but they do exist.

You know, 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 women.

I definitely avoided saunas when I was pregnant.

But it is, I think it’s very relevant for disabled people

and also people like that are sedentary,

have been sedentary most of their life.

Like my mother, I’ve been able to get her in the sauna

because she’s not, I mean,

I did get her on the Peloton once,

but it’s really much easier.

She feels like it’s a spa treatment

and it’s like she can listen to her music in there.

And 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 gerontology last year,

I guess, late last year.

And basically cardio respiratory fitness,

which is a marker of, it’s a marker of health.

Cardio respiratory 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 like 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 was 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

correlated 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.

And there’s, back to my worm studies I was doing,

I would elevate heat shock proteins in those 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.

So 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 a sauna.

So, 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 is protecting from Alzheimer’s disease

and other cardiovascular health as well as longevity.

So, 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,

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.

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 just worked on 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.

And they’re also activated by cold as well.

Cold shock does activate heat shock proteins,

not as robust.

Sulfurafane activates them.

Again, it’s one of the reasons

I think we should get all of these things

because they are more robust inputs.

Their 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 wanna get the most robust

from all of them, right?

I do.

So I mean, that’s why I wanna 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 like 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,

their FOXO3 is always active in those worms.

And they live like 100% longer.

And not only do they live longer,

I mean, they are like a very young worm.

I mean, they are like,

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.

And this was like back in the 90s.

And honestly, I’m not sure that anything has been

as exciting in the worm world since then.

But I thought, I mean, it was a really big finding.

The only caveat there is that the worms go

through this dour, it’s called a dour stage

when this happens,

when you decrease their insulin signaling and stuff.

And they like go into this like metabolic stasis.

Like they’re not eating as much or moving.

And so it’s like, okay, well, they live 100% longer,

but like they go into this weird state.

I know people like this, some in the longevity community.

I know who they are,

but they’ll get the last laugh because 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

when 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.

I actually have a, and they had to do it very seldom.

So it sounds like these protocols you’re describing,

20 minutes done four times per week,

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 of questions.

Can people use hot baths?

With the appropriate warning, of course,

that without getting into a 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, 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.

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 three, six months later, it’s back to normal.

Great, that’s 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,

you always say, what about cold showers?

And I always say, well, the studies have mainly been done

on immersion because it’s hard

to keep things controlled in cold showers.

It just doesn’t make for a very good experiment

because 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,

but 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 when 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 like 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.

I mean, it was like,

there was a study where they were looking at muscle disuse

and it was something like the local heat treatment

prevented like almost 40% of the muscle atrophy

from disuse.

So like, and it’s funny,

because I used to use this sauna

when I was injured and stuff.

I would go in the sauna,

because I didn’t know at the time

because I was a graduate student,

but I knew like just from experiments

that like, you know, like I’m not losing as much muscle.

I feel better.

Like I, you know, like at the time

I was reading a lot about the growth hormone

and stuff back then.

But, and I knew about heat shock proteins.

And so I kind of knew,

but that data wasn’t around yet.

And so now we have the data

and I’ve always like felt like I wasn’t losing my muscle

like I should have been when I was doing the sauna.

I was doing it literally seven days a week.

It was like 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 because of the,

it all depends on my schedule.

I also like to do long runs.

I really, it’s like long being like three miles,

not like Cam Haines, that’s too long.

But I really, for me,

and we were talking about this earlier,

like off camera that the runs for me

are for my brain and I 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 just, I miss my runs if I don’t do them.

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 think that I’d be exercising,

you know, 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.

Like you’re always wondering,

you’re always wanting to know,

you’re wanting to do the best.

Like if you don’t exercise,

you’re missing that essential dose.

And so that for me is the motivation,

the doping seeking thing I’m looking for.

Admittedly, I do not do enough strength training

and I have to do it.

I have to, I have to, I have to.

I’m like, I’m just,

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 nineties 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?

This is 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 then also just letting your ideas in 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.

And 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, it 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?

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.

It was a Nobel prize in 1908 for phototherapy for lupus.

So it’s not like a new thing,

the idea that red light and 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 mentioned 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 do have like, 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, it’s not activating it at a specific wavelength,

which is-

It’s usually so that the range that seems to be helpful.

And I have, 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 as such that it can travel down

through the deep layers of the dermis of the skin.

I, you know, 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

that I’ve talked about.

I think that would be, is, you know,

the potential effect on mitochondria is interesting.

I do think there’s a lack of really good solid evidence

in, you know, humans,

but that might only be because it’s just not studied enough.

And that’s usually the case.

So perhaps, you know, like there’s the Juve, right?

The Juve, they have those pant red light panels.

Juve and Cozy are the two ones I know, K-O-Z-E and Juve.

They’re there, as far as I know,

I’m probably gonna 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.

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 weigh-on therapy.

And they get people in infrared saunas

and then they wrap them in a towel

and like they stay warm for X amount.

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.

Like there’ve 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 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 four fold higher.

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.

But like a standard sauna is a heater

and the heater is 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.

I mean, that’s what you’re feeling

when you’re in the hot sauna.

And that for me takes a really long time

in the infrared sauna.

I get 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.


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 was mainly used in all these studies.

So we covered a lot of territory,

but I just want to thank you again.

It was extremely thorough and extremely informative.

I now have, 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 really awesome conversation, so I enjoyed it a lot.

Let’s do it again.



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