Dr. Rhonda Patrick: Micronutrients for Health & Longevity | Huberman Lab Podcast #70

- Welcome to the Huberman Lab Podcast,

where we discuss science and science-based tools

for everyday life.

[upbeat music]

I'm Andrew Huberman,

and I'm a professor of neurobiology and ophthalmology

at Stanford School of Medicine.

Today, my guest is Dr. Rhonda Patrick.

Dr. Patrick is known to some of you as a podcaster

and one of the premier educators

in the landscape of mitochondria, metabolism, stress,

and other aspects of brain and body health.

Her podcast, FoundMyFitness,

is one of the premier podcasts in the world

for disseminating knowledge

about how the brain and body work

and how we can use behavioral tools, micronutrients,

supplements and other protocols

in order to maximize our immediate and long-term health.

Dr. Patrick did her formal training in cell biology,

exploring the links between mitochondrial metabolism,

apoptosis, which is naturally occurring cell death,

which is a healthy form of cell death

that occurs in our brain and body throughout the lifespan,

and cancer biology.

She then went on to do postdoctoral training

with Dr. Bruce Ames,

investigating the effects of micronutrients,

meaning vitamins and minerals,

and how they affect metabolism, inflammation,

DNA damage, and the aging process.

She has published landmark review articles

and primary research,

meaning original research articles,

in some of the premier journals in the world,

including Science, Nature Cell Biology,

Trends in Cell Biology, and FASEB.

Indeed, Dr. Patrick is an expert

in an extraordinarily broad range of topics

that impact our health.

For today's episode, we focus primarily

on the major categories of micronutrients

that are essential for brain and body health.

I have to confess that before the discussion

with Dr. Patrick,

I was aware of only one of the categories

of micronutrients that we discuss,

and so you'll notice that I'm wrapped with attention

throughout the discussion.

And I think that you'll want to have a pen and paper handy

because she offers not only a very clear understanding

of the biological mechanisms

by which other micronutrients operate,

but some very clear and actionable tools and items

that we can all embark on

if we are to optimize our brain and body health.

We also discuss behavioral protocols.

Dr. Patrick is well known for her understanding

of the scientific literature on sauna

and the use of heat and cold for optimizing things

like metabolism, longevity, cardiovascular health,

and I'm delighted to say that we discus that as well,

and how behavioral protocols can interface

with supplement-based and nutritional protocols.

I'm confident that you'll learn a tremendous amount

of information from Dr. Patrick,

much of which is immediately actionable.

And if you're not already following and listening

to her excellent podcast, you'll absolutely want to do that.

It's foundmyfitness.com is the website

where you can get access to that podcast.

It's also on Apple and Spotify

and YouTube as FoundMyFitness.

Dr. Patrick also has a terrific newsletter

that I recommend signing up for.

It's foundmyfitness.com/newsletter is where you'll find it,

and it includes research on fasting, micronutrients,

sleep, depression, fitness, longevity, and far more,

along, of course, with actionable protocols.

I'm pleased to announce that the Huberman Lab Podcast

is now partnered with Momentous supplements.

Our motivation for partnering with Momentous

is to provide people one location where they can go

to access the highest quality supplements

in the specific dosages

that are best supported by the scientific research

and that are discussed during various episodes

of the Huberman Lab Podcast.

If you go to livemomentus.com/huberman,

you will see those formulations.

I should mention that we are going to add

more formulations in the months to come.

And you'll see specific suggestions

about how best to take those supplements,

meaning what dosages and times of day,

and, in fact, how to combine those supplements

with specific behavioral protocols

that have been discussed on the podcast

and are science supported

in order to drive the maximum benefit

from those supplements.

And many of you will probably also be pleased to learn

that Momentous ships not just within the United States

but also internationally.

So, once again, if you go to livemomentus.com/huberman,

you'll find what we firmly believe

to be the best quality supplements

in the precise dosages

and the best protocols for taking those supplements

along with the ideal behavioral protocols

to combine with those supplement formulations.

I'm pleased to announce that I'm hosting two live events

this May.

The first live event will be hosted

in Seattle, Washington, on May 17th.

The second live event will be hosted

in Portland, Oregon, on May 18th.

Both are part of a lecture series

entitled "The Brain Body Contract,"

during which I will discuss science and science-based tools

for mental health, physical health, and performance.

I should point out that,

while some of the material I'll cover will overlap

with information covered here on the Huberman Lab Podcast

and on various social media posts,

most of the information I will cover is going to be distinct

from information covered on the podcast or elsewhere.

So, once again, it's Seattle on May 17th,

Portland on May 18th.

You can access tickets by going to hubermanlab.com/tour,

and I hope to see you there.

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

is separate from my teaching and research roles at Stanford.

It is, however, part of my desire and effort

to bring zero cost to consumer information

about science and science-related tools

to the general public.

In keeping with that theme,

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

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And now for my discussion with Dr. Rhonda Patrick.

Rhonda, welcome.

This has been a long time coming.

Even longer than you know because, even before we discussed

you coming on this podcast as a guest,

I've been watching your content for a very long time.

So I want to start off by saying thank you.

You were the spearhead to break through

from academic science to public education.

So I consider you first in,

and the rest of us are just in your wake.

So, thank you for that. It's been-

- Oh, that is so kind.

Thank you. Thank you so much.

Well, it's absolutely true.

- I am so excited to be here

having a conversation with you.

- Thank you.

It's absolutely true.

If anyone does their research, they'll realize

that the statement I just made is absolutely true

and there isn't even a close second.

Any other public facing educators

that have formal science training

and do regular posting of content

came in several years after you initiated it,

so we're all grateful.

I have so many questions, but I want to start off

with kind of a new but old theme

that you're very familiar with.

So temperature is a powerful stimulus,

as we know, for biology,

and you've covered a lot of material

related to the utility of cold

but also the utility of heat,

and, as I learn more and more from your content

and from the various papers,

it seems that there's a bit of a conundrum

in that cold can stimulate a number of things,

like increases in metabolism, brown fat,

et cetera, et cetera.

Hopefully, you'll tell us more about those.

But heat seems to be able to do a lot of the same things.

And I wonder whether or not the discomfort of cold,

deliberate cold exposure, and the discomfort of heat

might be anchoring to the same pathway.

So, would you mind sharing with us

a little bit about what happens

when we get into a cold environment on purpose,

and what happens when we get

into a hot environment on purpose?

And I'm hoping that this might eventually lead us

to some point of convergent understanding, so if you would.

- I would love to. Let's take a step back.

I think you brought up a really important point here.

And I think that point

has to do with the intermittent challenging of yourself

and whether that is through temperature changes,

like cold or heat,

or through other types of stressors, like physical activity,

or perhaps even dietary compounds that are found in plants.

These are things like polyphenols or flavanols.

Humans, we evolved to intermittently challenge ourselves.

And before we had Instacart, where you could basically

just get your food delivered to you,

before the Industrial Revolution occurred,

we were out hunting.

And I say, we, not us but humans.

We were out gathering.

We were moving, and we had to be physically fit.

You couldn't catch your prey

if you were a sedentary slob, right?

You were moving, and you had to pick your berries.

You had to move.

And so physical activity was a part of everyday life,

and caloric restriction or intermittent fasting

was also a part of it.

This is another type of challenge.

We didn't always have a prey that we caught,

or maybe temperatures were such that there was nothing

for us to gather, right?

So food scarcity was something common

as well as eating plants,

so getting these compounds that I mentioned.

These are all types of stress, intermittent challenges,

that activate genetic pathways in our bodies.

These are often referred to in science

as stress response pathways

because they respond to a little bit of stress.

Physical activity is strenuous.

Fasting's a little bit stressful. Heat, cold.

These things are all types

of little intermittent challenges.

And there is a lot of crosstalk between these stressors

and the genetic pathways that they activate.

And these genetic pathways that are activated

help you deal with stress.

And they do it in a way that is not only beneficial

to help you deal with that little stressor,

exercise or heat,

it stays active, and it helps you deal with the stress

of normal metabolism, normal immune function happening,

just life, aging, right?

So this concept is referred to as hormesis.

This is a little bit of stressful challenge

that activates these stress response pathways

in a beneficial way, that is a net positive,

that actually has a very profound antioxidant,

anti-inflammatory response, or whatever the response is.

It could be the production of more stem cells.

These are cells that help regenerate

different cells within tissues,

or something like autophagy,

which is a process that can clear away

all the gunk inside of our cells,

pieces of DNA, protein aggregates.

So you'll find that the stress response pathways

are activated by a variety of stressors.

So, for example, one pathway is called heat shock proteins,

and, as their name would imply, one would go,

"Oh, they're activated by heat."

Well, correct. They are activated very robustly by heat.

And we can talk about that.

You can eat a plant like broccoli sprouts,

which is high in something called sulforaphane.

This is a compound that is sort of like a hormetic compound,

or, as David Sinclair likes to say,

it's a xenohormetic compound.

I love that. I love that term.

And it activates heat shock proteins among other things.

It also activates a very powerful detoxification pathway

called Nrf2, which helps you detoxify things

like carcinogens that you're exposed to.

Well, guess what? Heat activates that.

So what I'm getting at is there is overlap.

Cold also activates heat shock proteins.

You're like, "Really? Cold?" Yes, it activates.

These are stress response pathways,

and they are activated by various types of stressors.

Now, you're going to more robustly activate heat shock proteins

from heat versus cold, but there is some overlap.

So I think that sort of forms the foundation there.

- Yeah, that's very helpful.

And it brings to mind, in the context of the nervous system,

I always tell people you only have a small kit

of neurochemicals to work with.

There isn't dopamine for Netflix,

and then dopamine for relationship,

and dopamine for work, et cetera.

Dopamine is a generic pathway by which motivation, craving,

and pursuit emerge, et cetera,

just like adrenaline is a generic theme

of many different behaviors.

It seems that it is the job of biological systems

to be able to take a diverse range of inputs,

even unknown inputs.

Like, we don't know what technology

will look like in three years,

but you can bet that some of those novel technologies

will tap into the very systems that I'm talking about now.

And there certainly will be other stressors to come about

that will tap into these pathways.

I have two questions related to what you just said

before we talk a little bit more about cold and heat.

You mentioned plants as a route

to creating intermittent challenge.

There's a lot of debate, mostly online,

about whether or not plants are our friends

or plants are trying to kill us.

The extreme version from the carnivore types,

pure carnivore diet types,

is that plants are trying to kill us.

From the plant-based diet folks,

it seems like it's more about what's healthy

for the planet, animals, and maybe for us.

But, if we set aside that argument,

and we just raise the hypothesis

that plants have compounds that are bad for us,

but maybe by consuming them in small amounts,

they're creating this hormesis type scenario,

so then I think we conceivably solve the problem.

We could say, yes, plants are bad for us,

but, in small amounts, they provide this hormetic response

and they're good for us, right?

So, in the same way that too much heat is bad for us,

too much cold is bad for us, can kill us, can kill neurons,

but, appropriately dosed,

in an intermittent challenge type of scenario,

it can be good for us.

Is that how I should think about plants and these compounds?

Do you think of them as good for us or as bad for us?

They're a very sharp blade, and we want to use them potently.

- I actually think that it's almost impossible.

I mean, you'd have to eat nothing

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

The bioavailability of these compounds in the plants,

they're attached to a food matrix.

It's not like taking it in a supplement form as well.

It's such that it's very difficult to make it toxic.

Now, there are some cases,

for example, if you eat cabbage,

and I think there's some group in Africa or somewhere

that that's all they eat is cabbage,

and there is a goitrogen in cabbage.

It's not sulforaphane. It's another compound.

But that's all they eat, every day. Nothing but that.

- They get goiter. The thick neck.

- Yeah, and they're iodine deficient on top of that.

So I do think,

you can, of course, make.

I mean, there are types of plants that are toxic

in small quantities, right?

- Hemlock.

- [Rhonda] Hemlock, exactly.

- Will kill you.

Folks, don't play this game with hemlock.

- But you're not going to get poisoned

from eating your serving of broccoli at dinner, right?

So, I mean, it depends on the plant.

These generalizations are kind of,

they're just not useful,

and I think that a lot of people online in the blogosphere,

they gravitate towards them because it's just easier,

and it's a lot more sensational.

- I eat plants, meat, and starches.

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

- I do, too.

- I feel like it's rare to be an omnivore.

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

as you said, the blogosphere,

most people, I would say, 99% of people on the planet

are probably omnivores.

- Right.

- And someone will probably correct me,

but I doubt the number falls below 98.

- I think, if you look at data,

and when we have carnivore data, I can't wait to see it,

but, right now, it's a lot of,

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

and there's a lot of good starts with anecdotes,

but people change a thousand things at once,

and they don't realize that, but they do.

And so anecdotal data is only so good, right?

It's a starting point.

And so we don't really know long-term

what carnivore diets are going to do.

They may be beneficial short-term.

They may be beneficial for reasons

of elimination of other things.

Who knows, right? Lots of possibilities.

But I do think, with respect to plants,

that there's so much evidence,

like, for example, sulforaphane is one that I really like

because there's just evidence that sulforaphane

is a very powerful activator of the Nrf2 pathway.

And this is a pathway that regulates a lot of genes,

a lot of genes that are related to glutathione production,

genes that are involved in detoxifying compounds

that we're exposed to from our food,

like heterocyclic amines.

In fact, there have been GWAS studies.

These are studies that are genome-wide associated studies,

for people listening that aren't familiar.

People have a variety of versions of genes,

and we have a gene that's able to make heterocyclic amines

to basically detoxify it so it's not as harmful.

And people that don't have a certain version of that

that's doing it well

are very prone to colon cancer and increased cancer risk,

but if they eat a lot of broccoli

and cruciferous vegetables, that negates that risk

because they're getting sulforaphane,

which activates a lot of the glutathione transferase

and synthase genes.

So glutathione's a major antioxidant in our brain,

in our vascular system, in our body, basically.

So there's evidence that eating things like compounds

that are like sulforaphane or broccoli or broccoli spouts,

which have up to 100 times more sulforaphane

than broccoli, are activating glutathione in the brain.

There's human evidence of that.

I mean, that's amazing.

- [Andrew] That is amazing. - In Plasma. Yeah.

- Sorry to interrupt. I just want to make sure.

So broccoli sprouts are different than broccoli,

and you just told us that they're much richer

in these compounds.

So, note to self, I should have broccoli sprouts,

not just broccoli.

Can we cook the broccoli and still get these nutrients,

or do we have to eat it raw?

I confess, eating raw broccoli is really aversive to me.

- So the sulforaphane is formed

from a compound called glucoraphanin,

which is in the broccoli,

and the enzyme that converted into sulforaphane

is myrosinase, and it's heat sensitive.

So you do somewhat lower the sulforaphane levels

when you cook the broccoli.

However, there was a study a few years back

that showed adding one gram of mustard seed powder,

ground mustard seed powder,

which also contains the myrosinase enzyme,

to your cooked broccoli

increases the sulforaphane by fourfold, so...

- This is great 'cause, I confess,

I like broccoli if it's cooked to the appropriate density,

not too mushy but definitely not raw.

The idea of eating raw broccoli to me just sounds horrible,

but I like the way mustard seed sounds.

So just a little bit of mustard seed powder

added to the cooked broccoli

can recover some of these compounds.

- Yes, so what I do is I will lightly steam my broccoli,

and then I add a little bit of my Kerrygold butter,

and then I add some mustard seed powder on the top of that.

And it's got a little kick.

It's just a little spice.

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

It should have a little kick.

- And because I know people will want to know

how often and how much,

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

- Well, I had shifted to supplementation with sulforaphane.

I'm admitting right now that I've been terrible about it

the past, I don't know, six months or so.

- The supplementation

or the broccoli? - Yes, the supplementation.

And so there's another way to get.

There's another compound,

and it's actually called moringa.

And Dr. Jed Fahey, who's really the expert on sulforaphane.

He's a good friend of mine.

He's been on the podcast a couple of times.

He basically thinks,

and has done a lot of research on marina as well,

that it's like the cousin,

and it activates the Nrf2 pathways

similarly to sulforaphane.

And so I've been buying this Kuli Kuli moringa powder.

I don't have any affiliation with him.

- Kuli Kuli is a brand? - Kuli Kuli's the brand.

- That you have no affiliation to.

- I have no affiliation, but Jed Fahey has researched it,

like that specific brand, and so it's legit.

It's science backed

in terms of actually containing moringa and activating Nrf2.

And I add it to my smoothies.

So that's what I've been doing.

- What are some dose ranges?

And, of course, we give the usual recommendations

that people should talk to their physician,

et cetera, et cetera.

But, if people are going to, what do you take?

That's always the...

- A big, heaping tablespoon. - Let's take

the David Sinclairian approach,

where he'll talk about what he does,

as a way to deal with this.

Of course, everybody's different

and should, in all seriousness,

anytime you add or delete something from your consumption

should consult some trusted healthcare professional,

trusted by you.

Do you recall the dosages?

- I do a big, heaping tablespoon.

- So Kuli Kuli moringa. It sounds like a song.

- It's with a K. I know, it does.

But, for people also listening,

it's like, "Well, why would I do that?"

I mentioned the glutathione in the brain.

I mentioned it in plasma.

It's been shown to lower DNA damage in people,

in white blood cells.

There's been several different studies in China.

In China, there's a lot of air pollution.

And I mentioned that it's a very powerful activator of Nrf2.

And I know you're familiar with Nrf2.

Nrf2 is a transcription factor that is,

it is binding to a little specific sequence

in a variety of different genes, and it's turning them on,

or, in some cases, turning them off.

It's regulating what's being activated

or what's not being activated, being turned off.

And some of the genes are basically

these detoxifying pathways.

We talked a little bit about the glutathione,

but there's also ones that are involved

in airborne carcinogens, like benzene.

So benzene's found in air pollution.

I mean, cigarette smoke.

If you're smoking cigarettes still, please try to quit.

- Yeah, you're mutating your DNA.

- [Rhonda] Yeah, it's the worst.

- To say nothing of the lung cancer,

you're mutating your DNA.

- And heart disease risk. Heart disease risk.

But, anyways.

People, and this has been repeated in more than one study,

that literally after 24 hours of taking,

I can't remember off the top of my head

what the dose of sulforaphane from broccoli extract,

broccoli seed extract was,

or broccoli sprouts extract, not the seed.

It was the sprouts.

Anyways, they started excreting 60% benzene and acrolein.

That's something that we get in cooked food.

- It's coming out in their urine?

- Coming out in their urine. Yeah.

- Well, I'm not a smoker, and I have to be honest.

It's rare that I hear of a supplement for the first time

'cause I've been deep-diving on supplements

since I was in my teens.

This is fascinating,

and it brings back to this question that we had before,

and I appreciate that you've answered it very clearly.

Plants have compounds that are good for us.

They're not just stressing us.

They're activating pathways that are reparative.

That's what I'm taking away

from everything you're telling me.

- Right, and that our bodies,

we're supposed to be getting that stress

to have those pathways activated.

You know, right?

I mean, this is conserved among different animals.

This is something that is,

it's supposed to happen.

And, in our modern day world, we don't have to eat plants.

We don't have to move anywhere or exercise.

We don't have to go through periods of not eating food

because we can have it at our fingertips

at any second, right?

So, I mean, we've got this conundrum of,

we're never activating these stress response pathways

that we're supposed to activate.

We're supposed to.

- I find that fascinating, and again,

drawing a parallel to the nervous system,

so what I'm hearing you say is that, historically,

we would have to go through some stress,

some confront cold or confront heat,

or confront effort or hunger,

have to exercise, essentially,

in order to obtain these compounds,

and then those compounds are reparative.

Yeah, I feel that resembles the dopamine pathway.

I always say there's nothing wrong with dopamine.

People think about dopamine hits as bad or dopamine is bad.

There's absolutely nothing wrong with dopamine.

The problem is dopamine, especially high levels of dopamine,

released without the need for effort to access that dopamine

is problematic.

So a line of cocaine gives you a ton of dopamine

with no effort except to ingest the drug,

whereas working for four years or more to get your degree

will release a lot of dopamine

and a lot of cortisol along the way, as we know,

and it's considered a healthy accomplishment in most cases,

a tremendous amount.

We're approaching the spring,

and there'll be a lot of graduations.

Weddings are coming up now that the pandemic

is hopefully slowing.

And there'll be a lot of dopamine.

High levels of dopamine are great,

but only after the effort of having done something

in order to access it.

And so that's what I'm taking away from what you're saying

is that we need to go through this intermittent,

different types of intermittent challenge,

and we are rewarded with particular compounds

that are reparative, both for the challenge,

but then make us stronger.

Hormesis really is, it seems,

a case of what doesn't kill us, makes us stronger.

So you mentioned-

- Can I add to that

one thing you just said? - [Andrew] Please, please.

- Because this has been shown

with, for example, sulforaphane in animal studies,

you precondition, give the animal sulforaphane,

and then you expose them to hypoxia

or some kind of ischemic stroke condition,

whatever they do to induce that,

and the sulforaphane, it basically protects them.

Their precondition

and their stress response pathways are primed,

and so, when they're then exposed to the ischemic stroke,

their outcomes are so much better, so much better

than the animals that didn't get the sulforaphane

48 hours before or whatever it was.

And this has been shown in multiple animal studies

with sulforaphane specifically in the brain.

I know Mark Mattson. Dr Mark Mattson.

He's often thought of as the intermittent fasting king,

but he's a neuroscientist,

and he did publish some work

and talks about sulforaphane as well.

- I'm really glad you brought that up, that example up,

because many of the questions I get on social media

and elsewhere are about traumatic brain injury.

And TBI is just one example.

And people always think, "Oh, sports. It's football."

Whenever you say TBI, people always think football.

And I just want to just take a moment to editorialize.

90% or more of traumatic brain injury

is construction work, at-home accidents.

Football players, hockey players, martial artists

are a tiny fraction of the people who have TBI

and concussion of various kinds.

It just so happens that, within those communities,

many of them, 75% or more, experience those.

So it's salient within those communities,

but concussion is prominent.

People are always asking, "What can I do

"in order to offset brain injury?

"I had a concussion two years ago. What can I do?"

And it's been a tough question

because we really don't have anything for them.

I mean, you tell them sleep well, eat well, exercise,

but it sounds like some of these reparative pathways

either should be explored in the context of brain injury

or, I'm guessing, are being explored

in the context of brain injury.

- Yeah, so a couple of things there.

One is that, I mean, traumatic brain injury,

it's terrible, but it's so interesting

because it's also like literal, real-time brain aging.

You're able to accelerate it and understand.

So I often think of, when I think of traumatic brain injury,

I think of so much overlap between Alzheimer's disease

and dementia and these neurodegenerative diseases

because there are a lot of similarities there.

And so, sulforaphane, I personally think,

and I do think there's been some animal research

with TBI and sulforaphane,

mostly preconditioning rather than treatment.

So, again, it's like, well,

if you want a healthy lifestyle thing

and you're a construction worker,

or you're fill in the blank, that's going to.

I mean, anyone that drives a car,

you're at risk to some degree, right?

- [Andrew] Or bicycle. - Bicycle, yeah.

- Around Stanford, I would say people demonize motorcycles,

people demonize a lot of things,

but moving fast through space on a small object

next to a 3,000 pound vehicle,

I mean, we have a number of friends that have died.

We have a number of people with traumatic brain injury.

I'm not against cycling or cyclists,

but it's a risky sport by any stretch.

So, in taking things like moringa

or eating my broccoli sprouts,

maybe cooking them a little less

than I'm currently cooking them,

putting on the mustard seed.

Is there evidence that?

Well, first of all, Nrf2 is expressed in neurons,

so those cells should be protected.

Are there other cells of the body

that could possibly gain protection from these pathways?

- Well, lungs for one, but just even in plasma cells.

I think Nrf2 is pretty ubiquitously expressed.

Liver.

There's so many animal studies

that have looked at all those things.

I try to kind of gravitate towards human ones

'cause it's a lot more relevant.

But I think, overall, like I mentioned,

DNA damage lower.

It was like 24 or 34% lower in human blood cells

after broccoli sprout powder supplementation.

- [Andrew] Wow.

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

and I think I have the references on there to exact amounts.

I can't remember. - We can link to the video.

- But it's kind of an old video. It's 2016.

But I also had Jed on the podcast,

and he did talk about this.

But it's also been shown in randomized controlled trials

to help treat autism and autistic symptoms.

Yet again, it's doing interesting things in the brain,

and I think it does have something to do

with the oxidative stress, the glutathione,

which would be relevant for TBI treatment.

It hasn't been shown empirically

that that helps with treatment,

but I do think someone could do that study.

I think that it should be done, honestly,

because it's a low-hanging fruit,

I mean, if there's any impact.

And there is at least one preliminary study

that glutathione is increased in the brain

after humans are basically taking sulforaphane.

- Which is, really, for people listening,

that's so important because a number of compounds

that people take in supplement form

don't cross the blood-brain barrier,

or they get metabolized in ways

that what's listed on the bottle almost becomes irrelevant

for what your cells actually experience.

So that's very reassuring.

We will get back to heat and cold

and this theme that I tried to surface,

but I just find this too interesting

to diverge at this point from these themes.

So, what other compounds or micronutrients

do you place in the top tier of useful, interesting?

There are animal studies.

Maybe there are hopefully also some human studies.

We've talked about a few.

I know you've talked a lot about omega-3 fatty acids.

So, if you had to do your top three,

your superstars of nutrients for the brain and body,

sounds like we've got one set,

what would you put alongside them?

- Omega-3, the marine omega-3 fatty acids.

So these are found in marine types of animals,

fish, cold water fish, fatty fish.

So there's three fatty acids.

There's one from a plant,

and that's often referred to as ALA, people call it short,

alpha-linolenic acid,

and then there's eicosapentaenoic acid, or EPA,

and docosahexaenoic acid, which is DHA.

Yeah, but EPA- - I'm amazed you can pronounce

two of the most difficult words to pronounce and spell

right next to ophthalmology,

which, if you can spell it.

I know people who have appointments

in ophthalmology departments

that don't know how to spell ophthalmology.

Little secret. There's an extra P in there.

So the ALA.

I'm not going to attempt to pronounce it

because your pronunciation was perfect

of both of these two compounds.

And you said are marine sources, so fish,

so sardines, cod, this sort of thing, but what about krill?

I've seen krill oil.

A few years back, people were saying krill

is a better source for omega-3s than is fish oil.

I took some krill oil capsules,

made me itch all over, so I stopped.

- Do you have a shellfish allergy?

- No, I don't think so. - No, okay.

- I don't think so.

I'm not a big fan of shellfish,

but I'll have oysters every now and again,

or shrimp or something, and feel fine.

- Yeah, we can talk about sources.

So krill is a source

mostly of a type of DHA and EPA

that's in phospholipid form.

So it's a phosphatidylcholine omega-3 fatty acid,

and that's different than most of the,

well, if we're talking about fish oil supplements,

that's a different story,

but if you're talking about comparing fish

to eating krill, like we're talking about the food.

- Oh, I would never eat krill.

- Okay. Are we talking about the supplements?

- Yes, I apologize. - Fish oil supplements.

- Yeah, krill supplement versus fish oil supplement,

and, if it fits in the conversation,

talking about great sources of omega-3s in their whole form.

I have a bad feeling you're going to tell me sardines.

- Sardines are, yeah, they're awesome. Anyways.

- Except for the taste.

- And for the potential contaminants.

Mercury, I think, was one.

No. Yeah, it was mercury.

And Joe was telling me about,

he used to eat sardines everyday.

Joe Rogan was telling me

that he used to eat sardines every day,

and then he had really high mercury levels.

And I was really shocked because sardines are low

in the fish groups.

The higher up you get, like swordfish and sharks,

like, really high mercury

'cause they're eating all the other fish, right?

But I think some brands,

and if you look at ConsumerLab.

ConsumerLab, it's like a third-party site

that I'm not affiliated with,

but I'll use them because they do a lot of analysis

of different foods and supplements.

And so you can look at some of their sardines,

and they have a list of ones that are pretty decent.

But, anyways, back to your question

about fish oil supplements versus krill oil supplements.

So one of the major differences

is that fish oil supplements,

if you get a high quality one, it's in a triglyceride form.

So you've got a glycerol backbone

with three fatty acids that's attached,

and those are either DHA or the EPA.

Or, if you have a lower quality fish oil supplement,

then you have what's called ethyl ester form.

And, typically, the reason for that,

when fish oil is purified,

it's run through this column with alcohol or something.

They cleave it off, the glycerol backbone,

and then it's just kind of easier to leave it like that

than re-esterifying it, which costs more money.

So you can get it in ethyl ester form,

which isn't as bioavailable.

And, in fact, if you don't take it with food,

you're going to be in trouble.

You're not going to absorb much of it at all.

- Would you see this on the packaging?

Is it going to say it's in this ethyl form?

- Some official brands will put it on their website,

perhaps on their packaging,

but, most of the time, you'll have to dig for it

on the website and/or call them.

But I think, for the most part,

ones that are higher end will market it,

like triglyceride form.

And it's not that ethyl ester's bad.

It just means take it with food.

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

both of them actually, Lovaza,

which is a mixture of DHA and EPA,

as well as Vascepa, which is a highly purified EPA.

These are both prescribed by physicians

to patients with hypertriglyceridemia,

so high triglycerides among other things,

I think maybe dysregulation of lipids as well.

- This is amazing.

For people, so these are prescription drugs

that are essentially very high-potency, purified omega-3s,

but they're given to people for lipid issues.

So this is the treatment of issues with fat metabolism

by giving people fat.

- Yes.

- I just want to push home,

again, I'm not carnivore keto or anything, I'm an omnivore,

but to just push home that one thing that's so wonderful

that you've done over the years and you continue to do

is to move away from these very broad, sweeping statements

about fat is bad.

Here's a case where we're saying fat is not only good,

it can be used to combat issues with fat metabolism.

And fats are not just one thing. They're many things.

So anyway, I just want to put a little highlighter

and a point of appreciation there

and make sure that people are sensitized to the fact that,

if you hear that fat is bad,

you have to ask, what kind of fat?

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

Okay, so the triglyceride form

can be taken with or without food,

and there's prescription forms.

I don't know if I can get ahold

of the prescription form unless-

- You have high triglycerides.

- Or I have a friend with high triglycerides.

No. It's illegal, folks.

Don't share prescription drugs.

- Or you talk to your doctor and you say,

"I'm already taking this from..."

I mean, I don't know how it works. Anyways.

- What's the dosage that you recommend people get?

One way or another.

- All right, okay, so the dosage that physicians prescribe

for high triglycerides, for example, is four grams a day.

- Four grams of EPA.

- Yes, of the Vascepa.

I think Lovaza's also prescribed at four grams a day.

And you can get either of those from your physician.

My father-in-law just got one of 'em prescribed.

We were buying our own omega-3 for years and years.

It's like, hey, you can actually get this

and health insurance can cover it.

And it's a really purified form,

but you have to take it with food. That was the bottom line.

I've totally gone on tangents,

but you're asking more interesting questions anyway.

- Well, normally I ask about mechanism

and then I talk about protocols, but in the-

- Or the why.

- [Andrew] Or the why.

- I mean, we haven't gotten there yet.

- And we definitely will get there,

but I think a number of people nowadays

are just really excited about what they can do

for their health, and so, here,

we're just raising the importance of omega-3s,

and then we'll definitely get to the why

and the underlying mechanism. - Yeah, I think four grams is,

I mean, in fact,

Bill Harris, Dr. Bill Harris,

he's just one of the pioneers

on omega-3 fatty acid research.

He was on our podcast last August.

And he was saying the reason FDA chose that was literally

just because how much they could get people to take.

It wasn't like an upper end,

like anything above that is unsafe.

That wasn't the case.

I mean, it was just purely cost

and compliance,

so what they can get into a pill, the amount they can get,

and how many pills they can get people to take.

- I'm smiling because our good friend Satchin Panda

at the Salk Institute,

who's done a lot of important work on intermittent fasting

and other incredible work on circadian rhythms, et cetera.

When I was talking to him

in preparation for an episode on intermittent fasting,

I said, "Why the eight-hour feeding window?"

And he said, "Well, the graduate student

"who ran those studies had a partner."

I think it was a girlfriend, as I recall.

Hope I didn't get that backward.

And the partner said, "Listen, you can be in lab

"10 hours a day, but you can't be in lab 14 hours a day

"if you want this relationship to work."

And so it was eight hours of feeding window,

plus some measurements and time to walk into the lab,

park the car, et cetera.

And so the eight-hour feeding window

that everyone holds so holy

was actually just born out of this relationship

between these two graduate students.

Had they been single,

I was single all through graduate school,

or most of it anyway, and I lived in the lab.

So, if it'd been me, intermittent fasting

would mean eating 14 hours a day.

That was a joke.

Not a good one, but just want to make clear. I'm joking.

But the point that you're making is a really good one,

that the four gram amount

is not a threshold based on anything

except the threshold of people's willingness

to actually take this stuff.

And I think that's important for people to hear.

Because so often we hear the eight-hour feeding window,

four grams of EPA, 150 minutes of cardio,

and it's really a question of what you can reasonably do

in a study.

- So I take four grams a day.

I take two in the morning, two grams in the morning,

and I take two grams in the evening.

I take my EPA in the morning,

and I take my DHA in the evening.

- You split them.

- I do.

I don't know.

I don't think it's necessary, necessarily.

I just happen to get a certain fish oil supplement

that separates them.

And so, like Lovaza, Lovaza's a great one,

and it's all in one, and it's easier.

- What if someone doesn't have a prescription?

So I take over-the-counter fish oil.

I know I feel better

'cause I've done the experiment of going on and off.

I take them mainly for,

I don't have depression, but my mood is better.

My joints feel better. I just feel better.

And I like to think that my platelets are slipperier,

and they're cruising through any little obstructions

in my veins or arteries.

That's the image I have in my head,

but I don't have any data to support that part.

- Yeah, I mean, so, if you're asking for, like,

where do people get these fish oil supplements?

- Let's say I look at the bottle,

and it says two grams per serving,

but then I look, and it's 750 milligrams of EPA

or 1,000 milligrams of EPA.

Let's say half of it is EPA.

Then, do I want to hit a threshold of EPA

or a threshold of what's listed on the bottle,

on the front of the bottle?

Because my understanding

is that we need to hit a threshold level of EPA

in order to derive these important benefits.

- I think two grams is a good threshold.

Now, the International Fish Oil Standards, IFSO,

they have a website where they do third-party testing

of a ton of different fish oil supplements

from around the world, and they measure the concentration

of the omega-3 fatty acids in the actual supplement,

because nothing is ever what it says on the bottle,

and then they also measure contaminants,

so mercury, PCBs, dioxins,

things that you'd find potentially in fish

that are harmful to humans,

and they also measure mercury and then oxidized fatty acids.

So these omega-3 fatty acids

are polyunsaturated fatty acids,

which are extremely prone to oxidation.

So please keep your fish oil in the refrigerator

because it's colder.

Yeah, they're extremely prone. - Mine's in the cupboard,

so now I know.

- The shelf life's increased. Lower oxidation.

- No, it makes perfect sense. Yeah.

- So, anyways, they measure that.

And I typically like to look for,

they give you a total oxidation number.

It's called T-O-T-O-X.

TOTOX is what we call it for short.

And I like it to be at the least under 10,

ideally under six.

It's really hard to find all the right mixtures of things,

but people can go to this website,

and they can browse through the products.

I've put together an Excel sheet,

which I have a YouTube little screencast

that I'm yet to publish, press the publish button on,

but it, basically,

you have to go back and check and update

'cause these are from different lot numbers of the products.

They do have up to like 20, 27 or something.

And so I've gone through and found my top picks

of high EPA brands and high DHA brands.

If I were to buy some, the ones that I would choose

because of the low total oxidation

and the high concentration of either EPA or DHA.

Now, people can go and do this themselves.

It just takes some work.

- No, I'm glad that you did the work.

I'm going to put up a tweet every week.

- Oh no!

- With you tagged until this list is published online.

Sorry, Rhonda, but I'm going to do it.

I know it's very sadistic of me,

but in service to the community

and myself. - Yes,

and I chose five brands from each,

and I tried to find one in Europe

and one in Canada. - Great.

- So there's a great selection

of US and other. - Thank you

for doing that work.

I don't want to do that work, and I trust you.

So, yeah, I try and get two grams per day of EPA

from supplementation.

I'll now put it in the refrigerator.

Mood is better.

I made that decision mainly based on the data

that I'm aware of,

looking at comparison of people doing that

anywhere from two to four grams of EPA per day

compared to SSRIs, selective serotonin reuptake inhibitors,

in treatment of depression,

and I don't want to take an SSRI if I don't have to,

and fortunately, I don't have to,

but the data, by my read, are remarkable.

People that take these things in sufficient doses,

meaning the EPAs,

are able to get by with much lower dosages

of SSRIs for depression relief

or, in some cases, to come off their SSRIs completely

or avoid going on antidepressant medication.

Now, of course, this is not something people should cowboy.

Mental health issues are serious.

But what other reasons,

I'd love your thoughts on that, on the mental health part,

so maybe you could tell us what are some things

that getting to two to four grams of EPA per day

is going to help with in our brain and the rest of our body.

- So, do you know?

So I actually published a paper back in 2015

about the role of omega-3 and vitamin D in depression,

bipolar disorder, schizophrenia, and impulsive behavior.

But, so, within that paper,

doing background research,

and this was a review article, by the way,

I was just connecting dots 'cause I love doing that.

- I'm going to grab that paper.

I confess, I don't know the paper,

but I love quality reviews

because the references they're in are so useful.

- Well, there's a huge role for inflammation,

the cause of inflammation in depression.

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

years ago, back when I was publishing that work,

where people are injected with lipopolysaccharide.

This is something that we're generating from our gut,

mostly from our gut permeability, which happens a lot.

Endotoxin, it's also called.

It's endotoxin lipopolysaccharide.

It's basically the outer membrane of bacterial cells

when bacteria die, so like when the immune cells in our gut

come into contact with the bacteria

because we drank alcohol five days in a row or whatever,

we release endotoxin, or something stressed us out.

We release endotoxin into our body,

and that causes inflammation.

And so you can inject people with lipopolysaccharide

and cause depressive symptoms.

However, if you take those same cohort of people,

give them EPA,

and I think it was somewhere around two grams,

and then inject them with lipopolysaccharide.

We're establishing causation here, right?

It totally, the depressive symptoms, versus a placebo.

So the placebo was saline control.

So this was a placebo controlled

because obviously it's hugely important for depression.

It ameliorated the depressive symptoms

that was caused by lipopolysaccharide.

- Amazing, and LPS, lipopolysaccharide, is no joke.

Years ago, when I was working on thermal regulation,

we would inject animals with LPS to induce fever.

The vagus nerve registers the presence of LPS signals

to these particular hyperglycemic areas

and cranks up body temperature

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

Amazing.

So I will continue with my two grams per day.

Maybe I'll ramp it up to four.

I'm not doing the DHA separately.

There's DHA

in the same supplement. - Yes.

- [Andrew] Is that okay?

- Yes. Yeah, yeah.

And to kind of...

Boy, we've got a lot of things to hit back on

because one of your original questions

was krill oil versus fish oil.

- Yes, still in the cue.

- DHA, specifically,

in phospholipid form, it's more bioavailable.

So, if you're comparing exact quantity or concentration

in triglyceride form versus phospholipid form,

you will get more in your plasma cells,

in your plasma, plasma cell,

in your plasma with krill oil.

However, krill oil supplements are so low dose.

I mean, good luck getting two grams

of omega-3 from krill oil.

And also, krill oil supplements are notoriously rancid.

I don't know for whatever reason.

- Maybe that's what made me itchy all over.

- I think they're just...

I haven't found a good krill oil supplement.

I pretty much stay away from it.

I mean, if you smell it too,

I mean, it just smells rancid.

So, but the thing is,

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

yeah, something like that,

about DHA in phospholipid form getting into the brain

through a different mechanism than DHA in triglyceride form.

And so it's going through a transporter

called the MFSD2A transporter.

And I think it's very relevant for people

with an APOE4 allele, so-

- People with an Alzheimer's susceptibility.

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

and a gene called APOE4,

and, basically, it's APOE, but the four is referred to

as the bad kind of version of it.

This is something in our bodies. It's also in our brain.

And if people have one of these versions,

if they got one from their mom or their dad,

they have a twofold increased risk for Alzheimer's disease.

If they get two, which is much more,

it's less common.

I think it's like 2% of the population or something

has two alleles, but they have like a 10

or 11-fold increased risk of Alzheimer's disease.

So there is a role for phospholipid form DHA in the brain,

but you also make phospholipid DHA inside your body.

And you can do that by taking in more triglyceride forms.

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

So kind of back to the why for fish oil.

I personally think it is one of the most powerful,

anti-inflammatory things, dietary lifestyle,

things that we can get easily, relatively easily,

that is going to powerfully modulate the way you think,

the way you feel, and the way you age.

And a variety of different types of studies

kind of led me to that conclusion,

a variety of observational studies.

So there's been lots of work by Dr. Bill Harris

and his collaborators looking at,

it's called the Omega-3 Index.

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

So red blood cells turn over about every 120 days.

So it's a long-term marker of omega-3 status.

This is very different from 99.9% of any study you see

or any lab that you go to to get your omega-3 levels tested.

You're getting your plasma phospholipid levels tested,

which is kind of like you can think of it as,

what did I eat a couple days before?

Oh, I had fish. My omega-3 levels are great.

But did you eat fish like that every week,

or was it like you went out to dinner?

So it's not a great biomarker for long-term omega-3 status.

It's kind of like the fasting blood glucose levels

versus the HbA1c, which is like a long-term marker

of your blood glucose levels.

So the Omega-3 Index.

He's done a variety of studies, observational studies.

So, for people listening,

these are studies that are obviously flawed

because they're not establishing causality.

You're looking at people's lifestyles.

But, in the case of Bill Harris's work,

he's measuring something.

So he's measuring the Omega-3 Index.

And he's measuring the Omega-3 Index in people,

and then looking at their mortality risk, for example,

or their cardiovascular disease risk.

And what he has found is that,

first of all, standard American diet

has an Omega-3 Index of 5%.

Japan, by contrast, has an Omega-3 Index

of around 10 to 11%.

Big difference there.

And they also have about a five-year

increased life expectancy compared to people in the US.

- Do you think that's mainly due to their fish intake,

seafood intake?

- So what he showed was,

I think it's a big part of it.

I mean, you can't says it's the only thing,

but what he showed in his data was that,

and I think it was Framingham Study,

where he looked at the Omega-3 Index,

and people that had a Omega-3 Index of 4% or lower,

so close to what the standard American is

but a little bit lower,

they had a five-year decreased life expectancy

compared to people that had an 8% Omega-3 Index.

And so big difference there, right?

Five years life expectancy.

But here's the really interesting thing, Andrew.

He also looked at smokers,

smokers and their omega-3 levels,

and so he stratified it, and he found smokers

that had no omega-3 were like the worst of all.

I mean, it was just like worse, right?

We all know smoking is bad for us

and will take years off our life expectancy.

- [Andrew] Absolutely.

- But smokers that had the high level,

like smokers that were taking their fish oil or eating fish

or whatever it was they were doing to get them up to 8%,

they had the same life expectancy as non-smokers

with the low Omega-3 Index.

- [Andrew] Wow.

- Right? - Wow.

That's amazing.

And it's also amazing to me

that people still smoke cigarettes.

But I see a lot of people vaping,

and I know a lot of people consume cannabis.

Have there been any studies specifically of vaping

or people smoking marijuana?

- Life expectancy? - All-cause mortality.

- I haven't seen those. I haven't seen those.

- They're not motivated enough to come in

as research subjects.

That was, again, a poor joke.

It is hard to study people, marijuana use,

unless, I'm told by my colleagues that study this stuff,

unless you offer people marijuana,

in which case they'll do it.

But, again, they're actually not very good research subjects

in all seriousness 'cause they are not very motivated

or consistent, and they forget their appointments.

So that's incredible.

And you mentioned that the data on pollution

related to the plant compounds earlier.

So it's almost like these things are,

again, are acting in a reparative way.

- The omega-3s are, I mean,

they are resolving inflammation.

They're blunting inflammation.

They're doing so many different.

They affect so many different parts

of the inflammatory pathway,

which is, I think, plays a huge role in the way we age,

the way our brain ages, the way we feel,

our mood, our joints, all that.

And so it's amazing that it's not, you know.

- I love fish oil. I feel better when I take it.

I try to eat some fatty fish a couple times a week.

I do want to just touch on food sources for a moment.

First of all, are there plants that are rich in omega-3s?

And second, I have some friends who are really into meat.

I like meat a lot, my dad's Argentine,

but I don't eat very much of it.

I try and eat high quality meats

in relatively limited amounts, but I do eat pretty often.

But I've been told by these sources

of a questionable authority that,

if an animal grazes on really good grasses, for instance,

that the meat can contain a lot of omega-3s,

which, in principle, makes sense

based on this Omega-3 Index.

'Cause you're telling me that a lot of this omega-3

is sequestered into the red blood cells.

So, if I'm eating high quality, grass-fed meat

and the grasses had omega-3s,

do my steaks have omega-3s or no?

- So there was a study published

that compared conventional meat,

so meat that animals are fed corn or soy or whatever it is.

- Which is terrible. - [Rhonda] Yeah.

- For animals and people, as far as I can tell.

I'm sure I'll get some attacks, but that's okay.

I won't read those comments.

Again, a joke. I read all the comments.

But it seems to me that these animals

have to either be taking fish oil

or eat plants that are very rich in omega-3s

in order for the meat

to actually contain sufficient omega-3s.

- So the meat, comparing the conventional meat

to the grass-fed or pasture-raised cows or cattle,

there were higher levels of alpha-linolenic acid.

And ALA, it can be converted into EPA and DHA,

but the conversion is very inefficient

and very dependent on a variety of factors,

including genetics.

Genetics, a huge regulator.

Some people can do it much better.

Others, you're getting like 5% of conversion to EPA.

Estrogen is a major regulator of making that more efficient.

It makes sense because pregnancy,

when your estrogen just goes through the roof.

These omega-3 fatty acids play a very important role

in brain development.

Women are supposed to be converting any ALA they can

into the longer-chain omega-3 fatty acids.

So estrogen does affect that,

but I would say plant sources.

So, if you're looking for the ALA,

plant sources would be walnuts, flaxseeds.

Those are probably the highest.

But, if a person is a vegan or a vegetarian,

their best bet is to actually get microalgae oil.

And you can supplement with microalgae oil

because microalgae, they do make the DHA.

And so that would be a better source

for people that are vegetarian and vegan

rather than doing the flaxseed oil

because that conversion inefficiency,

the enzymes that convert ALA into EPA and DHA,

again, it's inefficient.

- And then, for people that eat fish,

sardines, you said.

- [Rhonda] Salmon.

- Salmon, and you have to eat the skin, as I understand.

- You don't have to, but it's good.

- [Andrew] It's rich with omegas.

- The oil, yeah.

And the reason I say,

I think the best would be wild Alaskan salmon

versus the farm-raised because the farm-raised, again,

they're feeding 'em corn.

They're feeding 'em grain and stuff.

- [Andrew] Really?

- And then, they give 'em astaxanthin.

So astaxanthin is a carotenoid.

It's the carotenoid that's in things like krill,

crustaceans that make their red pigment.

- Yeah, it's also being used now as a supplement,

and there's a prescription form

to try and rescue some age-related vision loss

because of the role of the vitamin A pathway

and photoreceptors.

- Yeah, well, actually the carotinoids themselves,

so like lutein, zeaxathin,

they're really good at sequestering singlet oxygen,

which is damaging, right?

- Yeah, as we age,

because the retinal cells, the cells of the eye

are so metabolically active,

they accumulate a lot of reactive oxygen species,

and mitochondrial repair

and limiting reactive oxygen species

is a major theme of trying to rescue vision.

That's a whole other podcast and story.

There's some really interesting data now

on the use of red light to try and trigger

these pathways. - I've seen some.

That's my good friend of many years and amazing scientist

Glen Jeffery's lab at University College London.

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

- I saw that study, like 2020, was it?

- Now, they have a second study.

- Oh, do they? They've done, okay.

- It's looking real.

- [Rhonda] That's exciting. - I mean, they're cautious.

They're appropriately British and cautious about it.

I always joke if those studies had been done over here,

everyone would already know about it.

Glen is a very conservative guy,

but they've done this stuff now in pigs, in rodent models,

and now also two studies in humans.

It's looking pretty interesting.

So sardines but also anchovies.

By the way, I hate all the food items that I'm describing.

I can barely tolerate salmon.

I don't like fish at all.

Actually, I like live fish. - So fish oil's good for you.

- I had fish tanks when I was a kid.

No, I find fish, unless it's in sushi form,

I find it absolutely repulsive, and I don't know why.

I probably have some mutation.

- So raw fish is actually higher in mercury than cooked.

- Okay, well, that's good.

I don't really like sushi that much anyway.

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

except I should eat these other fish sources

or supplement more heavily.

That's the message I'm getting.

- I eat sardines.

Every day, my first meal almost

is a can of sardines and an avocado.

- Avocado is good.

- I love it, yeah, with a little bit of lemon

and then some little hot sauce.

- Does avocado have omega-3s?

- Avocado is very good in monounsaturated fat.

It's not really high in polyunsaturated fat.

Omega-3, really, it's either the DHA and EPA

that's in the marine sources fish,

or it's the plant ALA source,

which is the flaxseed or the walnuts.

- It's rough.

I mean, all these companies now

are making these plant-based products that taste like meat.

My wish is that they would just make a fish

that tastes like a steak, but that's-

- The fish come out albino, the ones that they farm raise,

because they don't eat any of the-

- I'm joking.

I don't want a genetically modified fish

that tastes like a steak.

Although, I love the taste of steak.

The point here is that, if one doesn't see themselves

regularly consuming these fish sources of omega-3s,

it seems to me that the only way to really get them

is from supplementation.

- And supplementation is a good way to get a high dose.

And to get back to your dose point,

there was a couple of studies that, basically,

I think there was some way they showed that people

that are in the 4% Omega-3 Index range,

in order to get to the 8%,

the five-year increased life expectancy

if we're comparing the two groups,

was to supplement with at least two grams.

It was about two grams a day.

And I think it was a little bit less

if it was triglyceride form,

but I think two grams is a good, safe number.

So most Americans that are not eating a lot of fish

and they're not supplementing

are probably around a 4 to 5% Omega-3 Index.

And to get to the 8%.

And I think that's a good empirical way

of thinking about it, right?

Okay, well, I want to get to that 8%.

By the way, I'm almost 16% Omega-3 Index.

- Yeah, I was going to ask about testing.

So, where and how can somebody measure their Omega-3 Index?

Which, again, just to remind people,

is essentially the percentage of omega-3s

that you have in your blood

with the caveat that the Omega-3 Index

will be heavily biased by what you ate in the previous days.

- Not the Omega-3 Index.

Okay, so, the Omega-3- - Sorry, I misunderstood.

I thought you said, in red blood cells,

if I ate salmon two days ago,

my Omega-3 Index is going to go up.

- No, that was plasma.

- [Andrew] I misunderstood.

- So most people are measuring,

if you look at a lot of studies, and honestly, Andrew,

I think a lot of the reason for conflicting data

is because people are measuring plasma omega-3 levels.

- [Andrew] Okay.

- The phospholipids. It's in a phospholipid, right?

Your phospholipids are carrying things.

These are lipoproteins.

They're carrying things like omega-3

and triglycerides and stuff and shuttling 'em around.

The Omega-3 Index is actually in the red blood cells,

and red blood cells take 120 days to turn over.

So, if you're going to do a baseline test,

if you want to know before supplementing what your level is,

you have to wait 120 days before doing the second test

after supplementing to know how much you went up

because that's how long it takes

for your red blood cell to turn over.

So the Omega-3 Index.

Bill Harris has a company that he co-founded.

It's called OmegaQuant,

and they measure the Omega-3 Index.

They have a variety of different index tests.

You can do a basic one or a little more advanced.

- This is from a blood draw.

- It's a little blood spot thing, yeah.

And he uses money to funnel back into doing lipid research.

He's out there doing all sorts of interesting studies

on omega-3s, so it's great.

But the Omega-3 Index is great.

I think that, honestly, more people

and more researchers should be using it

because the conflicting data,

it always comes down to what we're measuring,

the sensitivity of it.

Are we even measuring anything?

So you're giving someone 500 milligrams of DHA,

and you don't see any effect.

Well, did you measure what their levels were?

And did you measure the Omega-3 Index?

There's all sorts of problems

with randomized controlled trials,

and I think that we need to, as scientists,

we need to come together and make some progress.

I mean, you know? Let's all talk to each other.

Let's figure things out.

This test is out there. It should be used.

It should be used not just by Bill's group, but everyone.

- Yeah, well, and I'm learning so much from you.

And I agree we need more collaboration.

I've always enjoyed really fruitful collaborations

in my lab at Stanford.

Collaborating is just so much more fun.

Online, there seems to be a bias more towards creating silos

as opposed to bridges,

but I appreciate that you bring up the need

for more collaboration.

And knowing which measures are best,

and, in this case, now, thank you for the clarification,

I understand this Omega-3 Index is going to be best.

So, basically, now, when I look at you,

I think, you are 16% omega-3.

- And dolphins are 19%. I'm almost-

- Is that your goal? You're trying to get there.

- It is. [laughs]

- Interesting.

Actually, they should probably do something

where you're trying to achieve the omega-3 ratio

of your favorite species.

Now that we've covered a bit of how to get these things

into one system, depending on what one eats, et cetera,

and some of the better measurements,

how is omega-3 and some of these other related lipids,

how are they having these positive effects?

In my mind, and this is incredibly elementary,

but my understanding is that, at some level,

they're making platelets more slippery.

Is that true or not?

I'm happy to be wrong.

How is it possibly impacting my mood?

Is it through the synthesis of membrane on neurons

that allows neurons to release more transmitter,

like serotonin and dopamine?

What are some of the purported, reported,

and known mechanisms?

- I think some of the most well-known mechanisms

do have to do with the omega-3 fatty acids

being very powerful regulators of the inflammatory process

in some way, shape, or form,

whether that has to do with resolvins that are produced

from the metabolites of DHA, for example.

Resolvins play a role in resolving inflammation.

You want your inflammatory response to be activated

when it's supposed to be,

but you want to resolve that inflammation

and the inflammatory response in a timely manner, right?

And resolvins help do that.

And so resolvins are one,

and then there's these specialized pro-mediating molecules,

the SPMs, that also help resolve the inflammation.

There's, like you mentioned,

the leukotrienes and prostaglandins,

and these things are being affected by EPA,

and they do affect platelets and platelet aggregation,

and they do affect that whole pathway as well.

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

And so, when we talk about inflammation,

honestly, that's a big general term,

but when you're talking about serotonin release

at the level of neurons,

we know that these inflammatory molecules

cross the blood-brain barrier.

I just mentioned ago about injecting people

with lipopolysaccharide and causing and depressive symptoms.

It's known that omega-3, actually specifically EPA,

is able to help serotonin.

Inflammation inhibits the release of serotonin,

and so EPA is actually able to blunt inflammatory responses

along with DHA as well.

DHA does that through resolvins and stuff.

And this then helps more serotonin be released

because you're not having so much inflammation

getting into the brain

and affecting serotonin release, right?

That's one mechanism.

And then, another would be,

well, DHA itself has been shown,

it's a very important fatty acid

that makes up cell membranes, many cell membranes,

including in our neurons.

And, as you very well know, Andrew,

the structure and function of receptors of transporters,

these membrane-bound proteins on the surface of our cells,

including neurons,

are affected by the membrane fluidity,

like how rigid and how fluid the cell membrane is,

and DHA plays a role in that.

And so, for example, in animal studies,

if you make an animal deficient in DHA,

their serotonin receptors, dopamine receptors,

they're affected because the structure of them is affected

through the fluidity of the membrane.

And so I think that's another mechanism.

And I'm talking sort of general

'cause I'm not a neuroscientist.

- No, but it makes perfect sense.

We know, for instance, neuroplasticity almost always

involves the recruitment of more receptors

or an improvement in some feature

of receptors to neurotransmitters.

And they literally move laterally in the membrane.

They kind of float around like little rafts.

Sometimes they are, in fact, in lipid rafts.

So it makes perfect sense that these molecules like DHA,

which are part of the structural fat of the neuron,

because, of course, the outsides of neurons

are basically fat,

not just the myelin that people have heard of,

but the actual membranes, that getting that right,

you wouldn't want it as rigid as concrete,

but you wouldn't want it as soft as...

Need to come up with something here.

What's that gooey stuff that kids play with?

It's like that goo. Anyway.

- Oh, yeah. - Yeah, it's disgusting,

and it's too soft to be a membrane for a neuron.

- You get it in those machines, like the claw machines.

- Someone put it in the comments

and tell me what that disgusting gooey stuff is.

You don't want your neurons to be that gooey,

and yet you don't want them to be like concrete either.

- It's a balance. Yeah. - It's a balance.

And, in mentioning DHA, I realize I'm backtracking,

but I want to make sure that we close

all the hatches for people.

We talked a lot about EPA,

but are food sources of DHA

that you find particularly attractive,

either by taste or by potency for DHA,

what are just a few that we could throw out?

Because I am aware that there are supplements

where you can get a nice ratio of EPA to DHA,

or you take them separately, as you do.

But if I want to make sure that I'm getting enough DHA,

what do I need to be sure I'm eating on a regular basis?

- Well, the fish is packaging the DHA and EPA in the ratio,

but I also do eat salmon roe, which is very salty,

and it's a really high source

of the phosphatidylcholine DHA

that we talked about. - So this is fish eggs.

- It is, and actually-

- [Andrew] That I like for some reason.

- Oh, do you?

- Yeah, so I'm discovering something about myself.

This was not meant to be nutritional psychotherapy,

but you're doing that for me anyway.

I'm discovering that, yeah, I like eating embryonic fish.

I just don't like eating the actual fish.

- Okay, well.

- Okay, so fish eggs are okay. So caviar, basically.

- Caviar, yes.

And that's a good source of the phospholipid form.

And I was consuming that a lot

because I wanted to get the phospholipid form.

- [Andrew] Yum!

- And it's actually really good.

There's been some animal studies

in piglets and rodents as well

showing that consuming phospholipid DHA

during fetal brain development

gets like 10 times more DHA in the brain.

Again, it's-

- Makes sense based on fetal development.

So, do I need to buy beluga caviar?

Stuff can get pretty expensive

at $200 a tin. - I don't think you need to.

I think it's a matter of preference.

And if you're supplementing

with your two to four grams of fish oil,

I mean, you're going to get phospholipid form anyway

'cause your body's going to make it.

- Okay, I've seen some containers

of what I assume to be quality fish eggs

that are not at the caviar level

that you can find in the better grocery stores

that aren't super expensive.

- [Rhonda] Right.

- I wouldn't dip as low as to go eat,

for instance, like fishing bait.

Like, when we were kids, we used to go fishing,

and you'd put the fish egg on the thing.

That's probably not good. - No.

- Although it's good enough for the fish apparently. Okay.

Only half joking here, folks.

I'm just trying to protect you from yourselves.

Don't get any crazy ideas about eating fishing bait.

Okay, so that's great to know.

So we have these plant-based compounds,

we have the omega-3s, so EPA, DHA,

and then you mentioned there's a third category.

What would you place in your third category

of foods or supplement-based nutrients

that our health, brain and/or body health,

can really benefit from?

- I mean, I think the most obvious would be vitamin D,

which is actually, as you know, a steroid hormone

that we produce when we're in the sun.

Depending on the time of year, we can make it in our skin.

And depending on how much melanin we have on our skin,

or whether or not we're wearing sunscreen or how old we are,

there's a sliding scale on how efficient that process is.

- As I understand, there's an inverse relationship,

where the darker your skin is naturally,

the more vitamin D you need to consume.

Is that right?

- Well, the darker your skin is, the harder it is.

So there was a study out of the University of Chicago,

this was several years ago,

where they looked at African Americans

and compared African Americans to Caucasians

with light skin, fair skin,

and how well they could make vitamin D from sun exposure,

and how long they had to be in the sun to make X amount.

And it turns out that African Americans

with darker pigmentation,

which protects them from the burning rays of the sun,

it's a natural sunscreen,

had to stay in the sun six times as long

as someone with none of that natural sunscreen.

So I think the take-home there is a lot of people

with darker skin living in Sub-Saharan Africa,

or people living in India with darker skin,

or in the Philippines,

you know, these equatorial regions

where you tend to see darker skin

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

- An adaptation.

- They are in the sun more,

and they're getting more vitamin D,

but people that maybe moved to United States,

to like Minnesota, or in a place where UVB radiation

isn't getting to the atmosphere 12 months out of the year.

It's only getting there four months, for example.

Or even living in our modern day society,

where people just don't go outside anymore.

I mean, we're inside.

We're at our laptops in school.

We're at work. We're in our cubicle, whatever.

So supplementation does play a major role,

not only for people with darker skin

that aren't outside all the time, but for everyone.

70% of the US population has inadequate vitamin D levels.

70 of the whole US. - [Andrew] Amazing.

- So this is everyone.

And so I think that insufficient levels

defined as less than 30 nanograms per milliliter,

and that's defined by the Endocrine Society,

looking at a lot of different aggregate studies,

all-cause mortality, for example.

There's been a lot of different meta analyses

of all-cause mortality studies,

where vitamin D levels really seem to be ideal

between 40 to 60 nanograms per milliliter.

And so, in order to get to that level,

if you are not outside all the time,

live in Southern California,

where you're always outside without sunscreen on.

I always wear sunscreen

because I'm trying to protect my skin

from so many wrinkles and stuff,

but also skin cancer is somewhat of an issue as well.

So, basically, the point is that vitamin D

is a steroid hormone, meaning it actually binds

to a receptor and another receptor dimerizes with it,

the retinoid receptor,

and that complex goes into the nucleus of a cell,

where your DNA is,

and it recognizes little sequences of DNA

called vitamin D response elements.

They're called VDREs.

They're specific sequences of DNA that this complex,

vitamin D bound with the vitamin D receptor,

goes inside and recognizes

and turns on a whole host of genes,

turns off a whole host of genes.

I mean, this is important stuff.

Imagine 70% of the population

having insufficient testosterone, right?

It's a steroid hormone.

- We might be headed there, but probably not.

No, I think that names are very important,

and I think that one of the issues is that vitamin D

is called vitamin D.

It's not called DHEA or variant blah, blah, blah.

It doesn't sound like a hormone.

I'm glad that you're mentioning skin as the major interface

between the environment and vitamin D synthesis

because a lot of people think of skin

as just a protective sheath around us

or something to adorn ourselves with earrings

or tattoos or whatever,

but skin obviously serves those roles,

but the skin is an endocrine organ.

It has the capacity to make things that impact hormones

and to make hormones.

There's this beautiful study out this last year.

This took place over in Israel,

where they had people get outside

for 20 or 30 minutes a day, three times a week,

exposing a culturally acceptable

yet substantial amount of their skin during that time,

and saw big increases in testosterone and estrogen.

And this is through a keratinocyte-linked pathway

involving p53.

This was done in humans,

but they did some knockout studies in parallel.

And what this study told me or reminded me

is that skin is an endocrine organ.

So the idea that sun could trigger the activation

of production of a hormone is really interesting

and makes total sense.

So, when vitamin D gets into cells,

and it's binding to these VDR

- [Rhonda] Es. - Es,

what sorts of things are they triggering?

So, for testosterone,

we know it's going to trigger protein synthesis,

muscle growth, tendon strength, et cetera,

With estrogen, it's going to keep your neurons going,

your joints feeling good.

I always remind people that, by the way,

'cause guys always seem to want

to increase their testosterone and reduce their estrogen.

Just remind people, if you reduce your estrogen, guys,

your libido will plummet to near zero.

Don't crush your estrogen.

It'll also make you stupid.

If you're not already stupid, it will make you stupid.

So estrogen's vitally important for males and females.

When vitamin D gets into cells,

what sorts of things is it stimulating?

- Okay, so, first of all, it's regulating more than 5%

of the protein-encoded human genome.

I say more than because, when I was looking at this data

really in depth starting in 2012 to 2014,

it was that, and then it's now grown.

But one of the important things that you'll find interesting

that I published on back in 2014

was that I'd gone through this big, published database,

where someone had published all these genes

they found VDREs in,

and basically I found that tryptophan hydroxylase-1

and tryptophan hydroxylase-2 was on there.

And so then I started looking at the sequence,

and I was doing some in silico work,

and it turns out that the VDREs in tryptophan hydroxylase-2.

So, for people listening, tryptophan hydroxylase

is an enzyme that converts tryptophan into serotonin.

So tryptophan is an amino acid that we get from our food.

You convert tryptophan into serotonin in the gut,

but you also do it in the brain.

However, serotonin does not cross the blood-brain barrier.

So tryptophan has to get into your brain,

and then you have to convert it to serotonin in your brain.

Well, the enzyme that does that in your brain

is called tryptophan hydroxylase-2,

and it's activated by vitamin D.

The one in the gut is actually tryptophan hydroxylase-1.

Some of my published work hypothesized

that it might actually be repressed by vitamin D

because it has a sequence.

The sequence itself, this 12 nucleotide sequence,

can determine, to some degree,

whether it's going to be activated or turned off.

And I was able to kind of look at that and think,

oh, maybe this and that.

Since then, there have been some groups

that have confirmed more with in vivo

and/or in vitro studies.

Mine was all in silico and all that stuff, but anyways.

So serotonin, a really important one.

This is regulating our immune cell, immune system.

It's regulating our blood pressure.

That's water retention.

Bone, of course, homeostasis.

5%. More than 5%.

I can't tell you. Like, so much.

- And with 70% of the US population deficient,

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

on a number of really important issues.

So supplementing vitamin D3 is what I normally hear.

I do.

I think I end up taking 5,000 IUs,

sometimes 10 IUs of vitamin D3 per day.

Just done that for a long time,

and I've had my levels tested and they're in range.

But I have a family member, I'll just mention this.

I have a family member who was not feeling well,

just kind of feeling off, a little low,

had some digestive issues,

this went on a long period of time,

was taking, on my recommendation, 15,000 IUs of D3

and was still deficient in D3.

Now takes, and I'm not suggesting anyone do this.

This is a special case, perhaps,

but no chronic illness that we're aware of.

Needs to take 30,000 IUs per day

in order to bring their D3 range just into normal,

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

they're a healthy weight, et cetera,

and it's made a tremendous difference

in terms of their mood.

Now, of course, this is correlative.

Now they feel better. They're doing it.

Who knows? They're probably also getting outside more.

But I think people need to get tested.

They need to get their D3 levels tested.

But where and what is a good starting range

for people to think about D3 supplementation,

and, again, foods that can increase D3?

- So vitamin D3 is a good way to supplement with it.

Vitamin D2 would be a plant source.

You often find it fortified in foods

like milk, usually D2.

- Does anyone still drink milk besides kids?

- Out here, it's like you can't find cows milk.

- [Rhonda] I mean, all the lattes

that you're getting. - Oat milk, soy milk.

What's the other one?

- [Rhonda] They're fortified in those as well.

- Oh, they are. Okay.

- [Rhonda] They are, yeah. They're fortified in-

- I have a hard time

finding cows milk. - Almond milk and oat milk

and all that stuff, yeah.

They're in all that stuff.

Vitamin D is naturally to some degree in fatty fish.

You think about cod liver oil, right?

It has vitamin D,

but you're not going to correct a deficiency

with eating fish for your vitamin D.

You're either going to correct it with sun exposure,

being in the right area, having the right amount of sun,

and being the right age,

because, as you get old, you become very inefficient

at converting vitamin D, making vitamin D3 in your skin.

- Well, that's probably what was going on here

'cause this person is getting up in their age.

- There's a lot of single nucleotide polymorphisms.

We talked about APOE4 before previously,

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

very common, actually.

In fact, I've had many people that have done

that exact same thing.

So measuring your vitamin D levels

before and after supplementation

is the only way you're going to figure that out, right?

Very important.

If you don't measure it, you don't know.

You can't know what you don't measure.

So there's a variety of SNPs

that basically make that conversion inefficient.

And, in fact, there've been a lot

of these Mendelian randomization studies.

So these are studies where scientists

will look at commons SNPs,

people that have these common variations of a gene.

That's more than 1% of the population.

So it's not a random mutation.

It's actually found in a sizeable percent of the population.

And then, they've looked at various outcomes.

And a lot of times, they'll look at genes

that are also involved in some kind of lifestyle factor,

so vitamin D,

and SNPs that basically make the conversion

of either vitamin D precursor into D3,

or D3 into 25-hydroxy vitamin D,

or into the active steroid hormone,

which is 1,25-dihydroxyvitamin D3.

And there's a variety of different SNPs that show.

So you're not looking at vitamin D levels at all.

You're looking at just the SNPs.

And you know, if they have it, they have low vitamin D.

So it's really a way of doing

a beautifully randomized controlled trial

with an observational study because you're not biased.

Vitamin D levels are also associated with health.

People that have higher vitamin D

are either outside more,

they're more physically active,

or they're aware of their health

and their supplementing, right?

So you always have to worry about that

when you're doing an observational study.

Dealing in randomization is beautiful for that reason,

where you're now just random.

People randomly have these genes,

and there's no health status.

If you have the SNP, like your friend,

like your family member was healthy and all.

They were healthy,

and yet they couldn't get their D levels up, right?

So these Mendelian randomization studies have found

that people that can't convert into the precursor,

the 25-hydroxy vitamin D, which is usually what's measured.

It's the most stable form of vitamin D in the body.

They have a higher all-cause mortality, if they can't do it.

So people that don't have it

have a lower all-cause mortality.

They have a higher respiratory-related mortality.

They have a higher cancer-related mortality.

So, to me... Now, why did I get on this rant?

Oh, because your family member.

So, basically, they also are more likely

to get multiple sclerosis.

This has all been done with Mendelian randomization.

And so it really does hammer home the importance

of measuring your vitamin D levels

and being very proactive about that.

I mean, you can get it done anywhere.

Your doctor will do it. You ask 'em to do it, you know.

So supplementation wise,

typically, if you don't have one of those SNPs,

for the most part, taking 1,000 IUs of vitamin D

will raise blood levels

by around five nanograms per milliliter.

So let's say you're deficient,

you're 20 nanograms per milliliter,

and you want to get to 40.

You're going to need at least 4,000 IUs,

if you are normal and don't have any of these SNPs

that change your metabolism of vitamin D, right?

- Does it matter when you take it relative to sun exposure,

time of day, with or without food?

- I've seen some not so great preliminary evidence

suggesting maybe time of day is important.

I don't think it.

Like, I can't seem to find anything that really suggests.

Because for it to actually be converted into the hormone,

I mean, it's stored.

- It's slow-acting.

These steroid hormones are slow-acting.

- Yeah, it's not like immediate thing.

So maybe we'll get some new data that's like otherwise,

but I just don't, yeah.

- It simplifies the problem anyway.

So, for people who are going to be stubborn

and not get their D3 levels tested or their D levels tested,

and simply say, "Oh, I'll just take some D3."

That was me, by the way, until I got tested.

I threw 5,000 IUs into the mix and figured,

well, it's not going to kill me.

It'll bring my vitamin D levels up.

I realize that's a bit of a coarse way to approach it,

but I feel fine, and I'm still breathing and ambulatory.

So, is that reasonable?

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

Again, just assuming that people are going to just jump to it

without the blood test.

- Of course, I think that, if we look at the literature,

the scientific literature,

it is extremely hard to get hypercalcemia,

which would be the major concern

with really high levels of vitamin D3 supplementation.

I mean, we're talking like hundreds of thousands

of IU a day for a long time.

- Hundreds of thousands. - Yes, yes.

Now, the upper tolerable intake was set

by the Medicine Institute to be 4,000.

It was kind of like one of those things where it's safe.

I personally take 5,000 IUs a day as well,

and my levels really hover around 50 nanograms per mill.

I don't put sunscreen on all the time.

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

but some of my skin is being exposed,

so I do make it from the sun as well.

- I'm glad you brought up the fact

that you keep arms exposed.

Because, in these studies that I mentioned before,

looking at sun exposure on skin

and increases in other hormones,

testosterone, estrogen, mainly,

it became clear from looking at those data

that the amount of skin that you expose is important,

which makes perfect sense once you hear that,

but I think most people are thinking,

oh, I'm out in the sun,

but are you wearing shorts and a t-shirt,

or are you wearing a sweatshirt and it's a hoodie?

Are you all covered up out in the sun?

Well, that might be great for setting your circadian rhythm

by way of light through the eyes

'cause that's the primary mechanism for that.

But seems to me that the more of your body surface

that you can safely and appropriately,

please, folks,

appropriately expose to the sun,

the more vitamin D you're going to create.

So laying out on your back deck in shorts and a t-shirt

with arms exposed and legs exposed

is a very different stimulus

than walking around in jeans and a sweatshirt.

- Absolutely. - Right? Okay, okay.

Especially if you have sunscreen on your face.

I know it almost seems like trivially simple,

but I'm not sure that people are used to thinking

about their skin as a interface to create these hormones.

- Yeah. - So surface area matters.

- And by the way, there have been studies looking at people

that are deficient in vitamin D.

In this case, it was African Americans

that were given a 4,000 IU a day vitamin D supplement

to bring them back to sufficient levels.

This was a smaller study than I would like,

but it reversed their epigenetic aging by three years.

Because, again, it's a hormone.

It's regulating more than 5%

of your protein-encoding human genome.

There's been studies looking

at vitamin D receptor knockout mice.

And I use this a lot in my presentations

when I'm talking about vitamin D and longevity.

If you look at these animals,

the vitamin D receptor, as I mentioned earlier,

vitamin D binds to the receptor,

and then it complexes with the retinoid receptor,

and they go into the nucleus as a complex

and turn on and turn off genes.

Well, if you get rid of that receptor,

which is what you can do in animal studies,

you can determine what effects there will be

with no vitamin D.

Like, how do you study no vitamin D?

And so what was found was that these animals,

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

'cause I think it might be embryonic lethal, but-

- [Andrew] Some hypomorph. - Yes.

- Which is basically geek speak for a gene

is vastly reduced in its function, number and function,

number, people know what I mean,

but isn't eliminated completely.

- Right, well, these animals,

if you look at them after the age of four months,

I mean, the mice look like.

I mean, they're accelerated aging.

They're wrinkled. They have no hair.

Their lifespan's shorter.

I mean, you can look at this animal

and not know anything about mice or work with them

and be like, "That animal looks like it's..."

Of course, mice lifespans are only like two,

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

- Looks like it went to graduate school twice.

- [Rhonda] Yeah.

- Actually, graduate school's a lot of fun.

I like to think I aged backwards in graduate school,

which is not true.

I look at the photos. I definitely aged forward.

You, on the other hand,

look exactly the same way you did 10 years ago.

I'm not saying that to flatter you,

but it's absolutely true.

I mean, the data or the data. It's remarkable.

So I'm definitely going to try

and get my omega-3 percentage up there.

I'm not going to hinge it all on that,

but clearly you're doing a lot of things right.

So, if I'm taking vitamin D3,

I still need to get out into the sun.

Correct? - Absolutely.

- Okay, I think a lot of people don't know that,

or, at least, I have family members

that have been a little bit resistant.

Like, "I take my vitamin D

"so I don't need to get outside as much."

I think people are really afraid of getting out into the sun

because they're worried about melanomas.

And, to be honest, I'm as scared of sunscreen

as I am of melanoma.

Some of the things in sunscreen are really spooky,

mainly the compound.

And here, I'm not one of these conspiracy.

I drink tap water. Listen, folks.

People cringe, but I drink tap water.

I have the occasional croissant or donut.

90%, 80% of the time,

I'm doing the right things, the right way, I think.

Although, I'm now going to improve on them

with this new knowledge.

But I don't like what I see in most sunscreens.

Because, if you look at these compounds,

they cross the blood-brain barrier.

I don't want compounds crossing the blood-brain barrier.

- Titanium dioxide?

- Dioxide, some of the triclosans

that are also in these cleansers.

I mean, once you know a little bit about neurons,

folks, you realize the neurons you got

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

There's a reason why there's a blood-brain barrier,

a blood-ovary, and a blood-testes barrier.

It's because the genetic material resides

in the testes, the ovaries, and the brain.

Those neurons don't turn over.

There are a few new neurons

but not that many unless you're a mouse, frankly.

And so protecting those is very key,

and a lot of the things in sunscreen

are downright dangerous.

So I think there are sunscreens that are safe,

but it's very hard to figure out

which sunscreens are free of these compounds.

I'm amazed that they're still on the market, frankly.

- I've always geared towards the ones with the minerals

that are reflecting it.

It is somewhat difficult to penetrate things

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

but I don't know.

Maybe some of these compounds get in there easily.

I have seen the evidence with some of those things.

- Yeah, there is some evidence they go transdermal.

- And they get in.

Okay, well, I know that some of them react with the sun

and, while they do protect from the UVA and/or B,

they form massive reactive oxygen species and carcinogen.

I mean, it's like the very thing you're trying

to protect yourself from might actually cause-

- [Andrew] Right.

- We don't know. It's completely speculation.

There is, I think, some more and more evidence coming out

with some of those compounds.

I can't remember all of 'em off the top of my head,

but a lot of high-end ones also have.

It's the chemical sunscreen ones.

- Right, right. - [Rhonda] The chemical ones.

- I'm proposing that we do a journal club.

A journal club, folks, is where academics get together.

Well, they read papers, then they get together,

and they pick apart the papers.

There's a strong correlation

between being an early graduate student

and being the most critical.

'Cause once you've actually published some papers,

you realize that, most studies, people are doing their best

within the context of what they can do.

But it'd be great to do a journal club

at some point about sunscreens

'cause I'd love to really figure out

what's in these compounds.

People are using them like crazy.

And I'm not one of these people who's like,

oh, I won't use commercial toothpaste

or anything like that.

Like I said, I drink tap water.

I use commercial toothpaste, whatever.

But when it comes to sunscreen, it freaks me out

because some of these compounds do go transdermal

and some of them cross the blood-brain barrier,

and I'd like to keep my neurons free of that stuff.

Anyway, we're speculating now.

- Wear a hat. - Wear a hat,

but get out in the sun and get your D3 levels up.

Okay, so, we talked about these plant-based compounds,

the omega-3s, and D3.

Unless there's something else

that you just absolutely must throw into the mix,

I probably will return us to the conversation

that I opened up with, which was about cold and heat,

which, admittedly, I pulled us off that path,

so I take full responsibility for that.

But before I do that,

I just want to offer you the opportunity.

Is there anything to supplement-based

or food-based compounds that you think are especially useful

for brain and/or body health?

- I do think magnesium is important in there as well.

I mean, I think, again, about 40% of the US population

doesn't get enough magnesium.

It's an essential mineral

we're supposed to be getting from our diet.

- Involved in everything.

- It is. It's also involved in vitamin D metabolism.

And, in fact, being deficient in magnesium

may make it more difficult

for you to actually make vitamin D hormone,

so that 1,25-dihyroxyvitamin D.

So one of those other factors, again,

we talked about genetics,

but there's also magnesium status as well.

Considering 40%, that's a big number.

Now, magnesium's also involved in making ATP,

the energetic currency of our cells.

Basically, all of our cells need ATP to do anything.

It's also involved in utilizing ATP

as well as DNA repair enzymes.

These are enzymes that are involved

in repairing damage to our DNA.

I personally think that magnesium insufficiency

causes an insidious type of damage daily

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

When you're deficient in vitamin C,

you're like, "My gums are falling apart.

"I have scurvy, right?"

But you can't see DNA damage.

You can't see it, but it's happening.

It's happening right now in my body,

and it's happening in your body.

It's happening. Normal metabolism is happening every day.

But we repair that damage.

We have repair enzymes in our body

called DNA repair enzymes.

They require magnesium.

Magnesium is a co-factor for them.

What that means, a co-factor means,

enzymes need it to function properly,

and so, without that co-factor,

they're not doing it properly.

The way I like to think about magnesium. It's easy.

'Cause people go, "What food should I eat?"

Naturally, that's the next question.

Well, magnesium is at the center of a chlorophyll molecule.

Chlorophyll is what gives plants their green color.

So dark, leafy greens are high in magnesium.

Basically, what does the 40%

insufficiency in the US tell us?

People aren't eating their greens.

They're not eating their greens.

They're eating their packaged food.

They're eating their processed food.

The standard American diet isn't really high

in dark, leafy greens.

So dark, leafy greens are how I like to get my magnesium.

I think it comes along with all these other important.

I mean, you get calcium in them. You get vitamin K1.

You're getting a lot of other micronutrients,

and you're getting other compounds that we don't know about,

and ones that we know about, like sulforaphane, right?

- As with broccoli,

do I need to eat the dark, leafy greens raw?

And, in this case, I'm a little more open to it

because I actually like the taste of, dare I say, kale.

And kale's a dark, leafy green, right?

- Yes, and it's high in lutein and zeaxanthin as well.

- I'm a trichromat, meaning I'm not color blind,

but I just want to make sure it falls

under the strict category.

'Cause every once in a while, I'm like,

"Oh, I eat my vegetables."

I like avocados,

and people remind me avocados are not a vegetable.

I love vegetables also.

So kale, what are some other examples?

- Kale, spinach, chard, like Swiss chard, rainbow chard,

romaine lettuce.

- Is the bitterness an important component to this?

- For magnesium, no, but for sulforaphane,

for cruciferous vegetables.

That would be the brassica family.

But your question about cooking them.

So magnesium, it is bound to the food matrix,

and it can be somewhat less bioavailable.

So cooking it can somewhat release the magnesium,

but it goes into the water too.

So you have to either steam it

or kind of like get your water in.

- You can drink the water.

- Yeah, I personally don't worry about it.

- Okay, great. - [Rhonda] I just don't worry.

- Well, if you don't worry, I'm not going to worry.

- But I also do supplement with magnesium.

So supplementation with magnesium,

I mean, we could go on and on.

Let's keep this short and sweet

because we're going to get back to the other stuff.

But it can cause GI distress at high doses.

I personally like to take around 130 or 135 milligrams.

That way, it's not like a huge bolus to my gut.

- But I think it depends on the form of magnesium too.

- Yes, yeah.

I mean, you can take magnesium threonate, for example,

and it doesn't affect the gut as much.

- Magnesium citrate.

- Citrate is what I take.

- [Rhonda] I take Thorne. - It's a pretty potent

gut stimulus.

I feel like it's a little bit harder to digest.

- 135 milligrams should be pretty good.

And citrate, actually,

oh boy, do we want to go here?

- I mean, it's up to you. We don't have to.

Personally, I've been supplementing with magnesium

for a long time.

I use threonate and bisglycinate

and malate for different reasons.

So, yes, I would love to go there if you're willing.

- I would say malate would be the best,

and that has to do with the short-chain fatty acids

being good for the gut and a lot of work done

by a former colleague of mine and good friend,

Mark Shigenaga, showing that the short-chain fatty acid,

citrate, malate, lactate,

but specifically malate, really, and lactate

are the major ones that get into the gut epithelial cells

and are an energy source for the mitochondria

and the goblet cells, so anyways,

whole other topic. - That's okay.

I take malate because I was told that it would be helpful.

First of all, it doesn't make me sleepy

like some of the other forms of magnesium,

which act as a mild sedative for me.

They do tap into the GABAergic pathway,

a neurotransmitter, folks,

that, in general, broad sweeping generalization here,

can have somewhat of a sedative quality,

which is why I take magnesium threonate

and/or bisglycinate before sleep,

30 to 60 minutes before sleep.

Definitely enhances my transition time to sleep

and the depth of sleep.

No question, in my experience.

There's some data that threonate can be neuroprotective,

although those studies are still ongoing.

I'm getting the sense that maybe you're

a little more skeptical of that than I am.

- Yeah, no, I've seen the studies with the threonate.

I think, looking at the actual data

from the one clinical study,

there wasn't statistical significance

until all three of the pieces of data were pulled together,

but that really could just be because their sample size

was too small, right?

- Yeah, I'm thinking that paired with the,

there's some work- - [Rhonda] The animal stuff.

- Yeah, Guosong Liu's work on.

This is getting kind of inside ball of neuroscience.

The quality of the labs matters, folks,

and that's something that's not accessible

to people outside of fields.

Guosong Liu and some of the other folks at that time at MIT,

I think very highly of their work.

And so the animal studies are indeed just animal studies,

but I was pretty impressed

by what they did in those studies.

Very pioneering when you think about this being done

10, 12, 15 years ago.

And then, yes, we need more human clinical data.

But, for me, I figured that, given the safety profile

of mag threonate, given that it helps me sleep better,

and sleeping better is just better for everything, frankly.

That's why I take it.

And bisglycinate and threonate

seem to be somewhat interchangeable,

but I don't know of any reports

that bisglycinate can be neuroprotective.

But malate I take during the daytime.

For me, and, again, this is subjective,

it has a tangible effect

in improving the recovery time from exercise.

I don't know that I've been sore from a workout

since I started taking malate,

and I used to get very sore

from even kind of trivial workouts.

So I don't know what's going on there, but I keep taking it.

- Malate, again, the short-chain fatty acid,

and when you do intense exercise,

you release endotoxin from your gut.

I'm just going back to the interesting work

'cause the malate being the short-chain fatty acid

and Mark Shigenaga showing,

this is all an animal research by the way,

but it was feeding these animals malate.

It really protected the gut, endotoxin release,

and it affected metabolic syndrome and all sorts of things.

But I think malates awesome,

and I always try to eat green apples.

They're really high in malic acid.

- [Andrew] Oh, good to know. - And tart cherries.

Tart cherries are really high in it as well.

- They also taste really good.

- But I was really interested

in the magnesium threonate stuff.

I take a supplement called Magnesi-Om by Moon Juice.

And it's like a little powder.

It's got a little bit of monk fruit, but it tastes good.

So I do it a little bit before bedtime as well.