Keto, Fasting, and Resilience | Dr. Dominic D’Agostino

Keto, Fasting, and Resilience | Dr. Dominic D’Agostino

July 31, 2019 6 By William Morgan


A good protocol which I think is, you know
Six six hours of eating and eighteen hours of fasting. So for me today is a day
I’m intermittent fasting. I will start eating
Maybe at about 3 p.m. And I will finish eating. I’ll have a nighttime snack at 9 p.m
Sadam how did you end up working with Navy SEALs?
I came in from sort of the the back end port like
the office of Navy research they fund
Projects under a particular program called the undersea medicine program and that’s for warfighter
performance and safety and
I was an avid diver as a PhD student and my under my postdoctoral fellowship research was really
developing technologies funded by the Department of Defense and the Navy
that would allow us to study the problems that the Navy SEAL divers have
And and also deep-sea divers so that could be oxygen toxicity as it pertains to the pulmonary system
oxygen toxicity as it pertains to the brain which causes seizures
decompression sickness nitrogen narcosis high pressure nervous syndrome
so these are all things that I studied sort of intensely in my postdoctoral fellowship years and
My project was funded to really study fundamentally
oxygen toxicity seizures and
We don’t know why they occur and at the time we didn’t know how to prevent them or how to predict them and prevent them
so
that led me down a path to basically look into anti-seizure strategies and to
You know being funded by the Navy is a little different than funded by the National Institutes of Health where?
You know, you’re required to just published high-impact peer-reviewed papers and get papers out
the military wants a deliverable so they want some little widget or
Deliverable at the end of your study to say look, you know
The guys can take this out to the field and it can apply to them or they can move it
whatever you develop into a large animal model like they study pigs for example, so
So my research initially really with the Navy SEALs and and office of Navy research
was to do very fundamental science in their basic science program and
To develop an anti-seizure neuroprotective strategy, so I was mostly focused on drugs at the time
but I realized that the anti-seizure drugs are really not very good for people with epilepsy or other seizure disorders and
In the process of looking and the process actually helping a friend in the UK in 2008 or six seven and eight
I
Suggested the ketogenic diet just by looking to see what two people
Do who have drug refractory or drug-resistant epilepsy and I discovered the ketogenic diet
Which I thought I knew about Atkins and but I didn’t actually know the history of the ketogenic diet as a very powerful
metabolic based program or
you know nutrition therapy that can prevent seizures and it was developed in the 1920s and I
decided to pitch this to the military as a
neuroprotective
strategy and
It took course it took about two years
from you know initial thought and
Studying and pitching it it took about two and a half years two years to get funding for that
So right now, you know going back about ten years ago eight years ago
The initial funding was to develop to understand why oxygen toxicity occurs
Biomedical countermeasures that can prevent option toxicity and then the last, you know five years developing
specific things formulas that the warfighter can take by mouth
That will instantly produce
Therapeutic ketosis to enhance their
Protection against oxygen toxicity cognitive performance physical performance
Anti-inflammatory effects because that’s a problem too. So we’re looking into a wide range of things on a particular
You know class of compounds and how that can be used
specifically in the context of extreme environments so as it pertains to the undersea environment
But now we’re working with NASA in the space environment
you know Air Force AFRL, you know altitude so
That’s that’s kind of like the very very general picture and we have lots of research projects that are run by
undergrads medical students PhD students postdoctoral fellows and
Then we collaborate with people all over the United States and all over the world
Actually, and we have a human study going on at Duke University right now looking at for example
nutritional ketosis in
Humans to prevent oxygen toxicity. I do a lot of rat studies in the lab
But we have actually got to the point now where we’re developing and moving some of these strategies
into more like human factors
Training or experimentation
Well, I want to talk more specifically about what it is that how this came about that Navy SEALs getting seizures
I don’t think people necessarily make that connection with diving. Could you explain these guys having having seizures? How does that work?
What could be going on there?
Yeah, absolutely. So if you just, you know do a search on
central nervous system oxygen toxicity or CNS oxygen toxicity
we know that oxygen toxicity of the CNS is a limitation of
Hyperbaric oxygen therapy which has about 14 different
fda-approved
Applications so you have things like decompression sickness, right if you get the bends you got to put somebody in a chamber
Press them and then bring them back up
You know to surface to prevent little bubbles from forming that’s called the bends or decompression sickness. That’s one application
Wound healing is probably the most popular most, you know used application
Ischemic wounds diabetic wounds radiation necrosis as it pertains to cancer treatment
carbon monoxide poisoning
So if you can for example think of carbon monoxide poisoning
So the carbon dioxide attaches to the hemoglobin molecule and it’s starving your body of oxygen, right?
So how do you get that molecule? It binds very tightly. You got to put the person inside a hyperbaric chamber
Press them with the maximum
Partial pressure of oxygen that you can you can use right but that a limitation of how high you can get
the oxygen level would be
oxygen toxicity seizures so you can really only go up to about 3 atmospheres of
oxygen
So we’re right now
I’m breathing air, which is
0.20 80 a of oxygen
It’s 20% oxygen when you’re breathing
100% oxygen that’s actually five times higher the level of oxygen that you’re breathing and it’s not toxic unless you’re in a hyperbaric
environment so
The partial pressure of oxygen is a function of the barometric pressure and the concentration, right?
so you factor those together and that’s that’s hyperbaric oxygen therapy and it’s a very
Oxygen as a drug. It’s a very powerful drug and it
At a certain level it becomes toxic to humans. So
so oxygen so
Navy SEAL divers are kind of unique and that they use a closed-circuit rebreather and
Meaning that the advantage is a stealth component. They can be underwater and there’s no bubbles coming up, right?
The disadvantage is that the oxygen concentration is very high. So it’s like for a dragger rebreather in similar units
It’s a hundred percent oxygen. So if they go down to just fifty feet of seawater
They have the potential to have an oxygen seizure within 10 to 12 minutes
So that’s not a lot of time right at just 50 feet of sea water
Typically, they dive pretty shallow
But in the event that the water is very clear and you have people looking for you overhead or you’re taking fire
Or you got to dive down to a ship or a bridge and plan a mine. You got to go deeper than that occasionally, so
to enhance the safety and performance and success of the mission you
Know we want to be able to
to ensure that the that these units can be used without the potential of oxygen toxicity seizures these
closed circuit rebreathers and
We don’t know how real to predict it. So if you could wear a little widget that could for example
detect heart rate variability or EEG activity or
you know respiratory rhythm generation or you know, we know that
there are
Perturbations in respiratory control that precede a seizure, you know from animal data. So we’re working on little
Strategies to predict the seizures, but most importantly we’re working on strategies that can
Give more bottom time
To the guys out in the field using this type of equipment and making it safer for them
and the development of these technologies these
these
countermeasures against oxygen toxicity have
utility for hyperbaric oxygen therapy making it safer and
Making it possible to allow people to get a much higher concentration of oxygen to to treat various
maladies or
toxic exposures for example like carbon dioxide
And to be able to do that in a much more safer way, you know or if someone’s prone to seizures
Perhaps they have a brain tumor and we’ve explored the use of hyperbaric oxygen therapy for cancer
But if you have a brain tumor you may be already susceptible to having a seizure but being in a state of therapeutic ketosis
May give you much more leverage and decrease your potential for having a seizure so you could potentially
utilize a therapy that would otherwise be
You know
counterindicated or contraindicated for that so
So we work in a lot of different areas now
my main thing was studying high pressure oxygen the negative effects of it and
Preventing that and now we actually have studies where we’re looking at hyperbaric oxygen therapy
for different applications
Right now they are
more or less
You know off-label use things like hyperbaric oxygen
For cancer, but unless you’ve had radiation therapy. So it is fda-approved for radiation necrosis
but we think that
high pressure oxygen can hyper oxygenate tumor tissue
reverse tumor hypoxia and shut off some of the gene drivers like if one alpha veg F and various factors that
Contribute to cancer growth in proliferation also by hyper oxygenating the tumor tissue
It increases reactive oxygen species to the point where you can overwhelm
The cancers antioxidant capacity and it sensitizes that cancer tissue to other forms of therapy
Right and radiation kind of works the same way radiation kills cancer cells through reactive oxygen species hyperbaric oxygen therapy
Just does it more gentle in a more gentle fashion. So we’re exploring the use of
So out of my military funded research came the observation
Because we have hyperbaric atomic force microscopy hyperbaric laser scanning confocal microscopy
We have unique technologies that no one else really has in the world. It allowed us to to look at
Cancer cells for example, and we do human dermal fiberglass and different type different types of cells
We observed that in cancer cells they over produce oxygen free radicals
Under graded levels of oxygen and that oxygen
was
Would kill those cancer cells whereas normal healthy cells were
Resilient against a similar
level of oxygen so that led us down a path which was kind of getting off track in some ways, but
Led us down a whole path of exploring
hyperbaric oxygen and other
modalities for
Cancer treatment as an adjuvant to different therapies. We’re exploring
right now so a little bit off topic, but that now I can say
we have about a third to
maybe half of the lab is studying cancer and different projects related to cancer and
using hyperbaric oxygen in combination with other things
so that could be a whole nother podcast, but for him, but that was that project evolved out of
Research and an observation from equipment that was funded by the Department of Defense with what’s called a Durov grant it
allows us to buy and
Develop and use that equipment for very novel
Somewhat esoteric projects, you know, you know looking at you know
CNS oxygen toxicity or the mitochondria of neurons
During a po2 equivalent of a Navy SEAL dive operation sort of scenario
Well done, you are you’re blowing my mind. You’re all over. There’s so many amazing things
I didn’t mean to go off in different different areas, but
What maybe you’re you’re people to know that?
Military research, you know just like NASA research has very broad applications and a lot of the technologies that we use today
you know GPS other things really evolved out of
Military funded research
Absolutely. Yeah
My graduate work before I was in the Navy was a study of people with a disease called spinal muscular atrophy
And it was it was Department of Defense funded and you know, people don’t always make those connections
But it’s amazing how how it does play into so many so many different fields of research as well
Yeah, and and while I was there also, my principal investigator was dr. Darryl DeVivo. He
vivos disease or glue blunt about
Absolutely. I know dr. DeVivo. Yeah, yeah
Yeah, we’re actually funded by the glucose transporter type one deficiency syndrome foundation
So we have glut Wendie mice where we don’t we just published a paper last
Two weeks ago looking at the effects of anesthesia on the glut1 mice so I know dr
clapper who sort of may be his protege and
Yeah, I’ve met with dr. Diva because I present at the glut1 deficiency Foundation conferences
And yeah, very cool that yeah, you know him small world. Yeah, maybe we’ve crossed paths before then
Yeah in working with him and on gluten deficiency syndrome
There was talk of the ketogenic diet epitaph. Yes. It was new to me. I just saw these amazing
slides where you’d see a
child who was having seizures that were
debilitating and then all of a sudden I’d say then the child did the the ketogenic diet and who the child walking upright and
healthy and alert and and things can you explain how there’s in a
History of this ketogenic diet that it’s not just a new trend in 2018 and it’s something that’s been around for a while
Yeah, yeah, it’s been around
well, I mean
fasting ketosis we could say has been used for millennia dating back to the times of Hippocrates like
you know 400 BC or more and it was observed that fasting could quote-unquote cure seizures and
Actually would work for some time after even after initiating food again
But fasting in that context was really not sustainable
Right because you you have to eat again and then it takes you out of fasting ketosis
so a lot of the benefits were derived from
the the metabolic
physiological state of fasting which is a suppression of the hormone insulin and also a
decrease in some extent of glucose levels and also in elevation of ketone bodies and
a
Metabolic based therapy was developed at the Mayo Clinic’s in in the early 1920s
and this was the ketogenic diet which
incorporated a macronutrient ratio, that was very high in fat about 90 percent fat and
It had adequate amount of protein to prevent protein malnutrition
With the least amount of carbohydrates possible, you know 0 to maybe 5% if that and consuming this diet produced
a
Metabolic physiology that was in many ways mimicked the state of fasting in a you caloric diet
Meaning that you were getting the calories that you needed to sustain
You know growth and repair and your weight maintenance and that this this nutritional ketosis
Was a means to induce
Therapeutic ketosis and then that had in and of itself just through a dietary means an ability to metabolically manage
seizure disorders
Independent of the etiology so which is interesting because you know, whether you have temporal lobe epilepsy
glucose transporter deficiency syndrome now, we know Angelman syndrome or
absence seizures even different types of seizures the ketogenic diet tends to work and and now even you know a
century later
it tends to work better than the
Drugs in most cases when drugs fail they people are put on a ketogenic diet
especially for kids it’s about
two-thirds of the kids respond favorably even after multiple drugs fail
so the question could be like why wouldn’t kids use this first because many of the
Anti-seizure drugs do cause developmental delays that may not be reversible in kids. So if you load a child up with
You know phenobarbital or different types of anti-seizure drugs
It can actually impact their
Development their brain development and then you don’t you don’t get that back it can you know impact their IQ and things?
What with the ketogenic diet that doesn’t happen. I mean it may actually have some cognitive enhancing properties maybe
For different subsets of people. So so the dye has been around for a long time
It’s use was marginalized in the nineteen late 1950s 60s and 70s and even 80s
When drugs came online and then Jim Abrams of the Charlie foundation the Hollywood producer his son Charlie
Was stricken with seizures was not controlled by multiple
drugs and
he was really upset that his son was not offered this as a therapy and
they initiated the diet at Johns Hopkins and
He became very vocal about the ketogenic diet for epilepsy
He was on Dateline NBC in the mid to late 90s and then Meryl Streep came on and did a movie about the ketogenic diet
Most people don’t know a Meryl Streep did a movie about the ketogenic diet and that was called first
You know harm and that brought more publicity to the ketogenic diet
For its use in Neurology and it still remains the standard of care in Neurology for drug-resistant epilepsy. It’s not the first line of treatment
But it works for glucose transporter deficiency syndrome where there’s essentially
Hypoglycemia in the cerebrospinal fluid because you can’t transport glucose across the blood-brain barrier
an elevation of ketones in the blood will readily cross the blood-brain barrier and
Restore brain energy metabolism and even neurotransmitter production like in kids and adults that have glut1 deficiency
So it is really a life-saving therapy for that disorder and many other even metabolic disorders pdh
Deficiency, I mean there’s all different types of disorders. It’s used for
And now we explore its application for you know
A lot of other things we’re looking at kabuki syndrome right now, and we’re starting a new project
kabuki syndrome is essentially a balance between
Gene repression and gene expression and in elevation of beta-hydroxybutyrate
Functions as something called a histone deacetylase inhibitor
Which can actually turn on the expression of genes that are otherwise silenced with this genetic disorder
so even in the presence of a persistent molecular pathology
the ketogenic diet by virtue of elevating beta-hydroxybutyrate which is a class 1 class 2 h dag inhibitor can
epigenetically
enhance and
restore normal brain function in the Kabuki mouse model it actually
It’s it saves the dentate gyrus neurons and rescues them from being degraded
So we are doing work on that now in the lab and just starting that up and the idea is to rapidly move that into
a
human therapy with kids and
Elevating that endogenous metabolite that we know functions as an h-back inhibitor
There’s an experimental drug called AR 42, but it’s not available yet for kids that have this
But beta hydroxy butyrate works just as good or better than AR 42, which is not yet available
So our lab is actually working
to
logistically right now set up everything that’s necessary to do a preclinical animal model study that will hopefully
parlay that into a
human clinical trial on something like kabuki syndrome
so
You know basically using ketones as an epigenetic regulator to basically alter gene function to restore
Some sort of normalcy and people who have this genetic disorder and for those who aren’t familiar with epigenetics
Could you kind of kind of explain because I think when people hear ketogenic diet or even if they know what bhp is
The idea of it functioning as a way that affects genetics is maybe new for a lot of folks
yeah, yep, so think about your
You know your your genome your normal genome we go to 23andme and we get our genome right and that’s kind of a
Written in stone. I guess you could say, you know
That’s that’s kind of our genome. But or we used to think that right, but there are processes that happen in the body
that
Allow us to go in there with more or less a repair kit and and alter
The genes in a way or the expression of various genes
To alter those expressions to influence our genome and and we call that
epigenetics so epigenetic is it’s sort of a above the genome right uppy and it’s the process in which
That our body has the ability to alter the expression of various genes and even to some extent
change our genome over time and that could be
environmental factors that could be drugs do this
that could be
You know metabolism fasting, you know now we’re realizing that
Metabolites just are not energy substrates that these metabolites like beta-hydroxybutyrate in particular
Have a have a functions have the signaling functions in our body that
in some ways can impact the expression or repression of different genes and
We are just going down in that direction when I started this research in ten years ago
We only knew of ketones as an alternative energy fuel
Mostly for the brain but over the years we’ve discovered that
They can influence gene expression that they can that there’s a toan receptor that they can in
Influence an inflammatory pathway that the drug companies are scrambling to design a drug to inhibit
You know that the beta-hydroxybutyrate can do that. So these are all
Things that sort of have popped out of the data and published not all in our lab actually most of it ins published by other
very big high impact
you know journals and and labs that have really teased out the molecular pathways that
have a really
Been elucidated and and more needs to be sort of determined exactly how some of these pathways are influenced
but one of the most exciting one to us is being able to
Alter our genes right through altering epigenetics, which is being able to edit in some ways
or influence the expression of various
gene pathways
And so for people who want all these benefits of this diet, what would are what are other other benefits?
I’ve heard you talk about things with austere environments your own work with NASA
For athletes, how does this this change in your diet?
Translate to so many of these things and what are those things that people could look for?
sure, like
this resource is right now at its infancy, so
the the use of the ketogenic diet as a
means to
enhance resilience in an extreme environment
So, you know, I’ve done enough experiments and rodent models to know that being in a state of therapeutic ketosis
Makes the rat what we call, you know from our drug studies a super rat
So basically when you put a rat into a state of ketosis and elevate its ketones
To the same level that would be achieved after me fasting seven days
That rat is 600 percent more resilient against oxygen toxicity seizures
and we’ve never been able to achieve that with any drug even and even like
Anti-seizure compounds that are so powerful that are not on the market yet. They have, you know side effects
We can’t even get that’s never protection from that
So this has work done, you know about eight years ago
so the question is
How do we leverage this technology? How do we develop it into a way that’s palatable. That’s tolerable
That is fda-approved. So we’re working on that well
we’re working on the use of these compounds for different childhood disorders and that
May set a precedent or a pathway for us to you know, get some of the more powerful
Compounds for use in Special Operations community things like that
So we do know that the ketogenic diet has a macronutrient ratio. That’s mostly fat and ketones are
the fourth macronutrient I like to say because they are calorie containing substances when we
consume them if we ate nothing else and
studies on dogs have been done where you consume something like 1/3 butanediol and it can sustain performance on a treadmill for
For a long time and that compound is not ketones are not classified as a macronutrient yet
So there are carbo hard carbohydrates proteins and fat, right?
So they are I think of them as a water-soluble fat molecule that can readily cross the blood-brain barrier
So the advantages to the warfighter or NASA, you know personnel would be the energy density is quite higher
Right. So the key of junk diet if we’re just looking at macronutrient
Profile and I’ve had some of the engineers do calculations on a four to six man crew to Mars and back it ends up saving
about two large SUV’s full of weight
so in food
If it’s a two one half or two year mission
so that that’s a significant amount of weight when because the energy density you have nine calories per gram as you know for
For fat and four calories per gram for carbohydrates and protein
So there’s shifting the macronutrient ratio instead of 70% fat or carbohydrates you make that 70% fat
Like right there, you are more than doubling sort of the energy density, right so may major logistical
advantages
Which the engineers love, you know, I’m interested in more the more of it as a bio
Sort of a biological countermeasure against those environments which could be the undersea environment as you know
hypoxia, or hypo
So there is a satiety factor to so when you’re adapted when your body is fat adapted and what we call keto adapted
the
you don’t get hungry so you can in the absence of food or if you’re in austere conditions and
your blood glucose levels drop
You are going to brain fog and a pretty dramatic
Predictable decrease in cognitive and physical performance if you are adapted to ketones
The ketone levels when they’re elevated in your blood and you go
hypoglycemics you’re asymptomatic for
hypoglycemia, so you can even in subjects that were fasted for you know forty days and they injected them with insulin they could
you know readily do cognitive, you know function tests and be fine so that in and of itself I think is
Is a major advantage?
Obviously a major advantages and there’s no other fuel that I know of that could really do that
you know that that could make you asymptomatic for
Hypoglycemia, when there’s an absence of food availability our body’s kind of do that naturally when we fast, you know
But being keto adapted allows you to do that very quickly
And once you’ve done the ketogenic diet and go back to a high
carbohydrate diet and then go back to a ketogenic diet you make ketones about twice as fast because you’ve
Upregulated a lot of the enzymatic pathways catalytic enzymes and transporters
That readily it’s almost like you activate a genetic program
That we call it we call it metabolic memory
You know when you workout in the gym and you work up to you know?
A 500 pound deadlift it might take you like, you know, ten years to do that, right?
but then you stop for six months and you get back in the gym again and about six or seven eight weeks you could get
Back up to that fight. So your metabolism, I think and this is stuff we’re looking at now
It’s kind of the same way. Once you’ve acclimated your body to be keto adapted that you can readily go in and out
We’re starting to see that has not been studied. So what I’m saying here, I guess I’ll have to stay step speculation
But as a scientist, you know, I’ve done it on myself and we have some rat data, you know
Hopefully we’ll publish that soon with it with our colleagues. So the satiety factor and ketones are anti catabolic
That’s their evolutionary function if we did not go into a state of ketosis
we would catabolize all our
Gluconeogenic amino acids in our skeletal muscle and we’d waste away in about two weeks and die probably of cardiac failure
but because we have essentially an endless supply of body fat even a lean person has like twenty to thirty thousand calories a
Body fat that body fats liberated converted to ketones and then those ketones are profoundly anti catabolic
So they prevent many of the proteolytic pathways and that they are very protein sparing we say so that’s their function
So it’s a satiety factor the energy density the protein sparing
And some of the stuff that we’re looking at now with NASA extreme environment Mission Operations
I was on a crew member for 22 which is working with astronauts in an undersea environment where we
Sort of are looking at a variety of different things and my wife will be on Nemo 23 and that’s coming up
We’re preparing for that. So I’ve noticed in myself that the requirement for sleep is less about slightly less maybe about 30
30 minutes less and the percentage of deep sleep is higher. So instead of getting
You know
60 minutes of deep sleep each night or 70 minutes if I’m at Iquitos if I’m in ketosis
I routinely get about 90 minutes of deep sleep to two hours of deep sleep 220 minutes
My sleep is very deep and my sleep architecture
My sleep timing is less and my sleep architecture is more and then I’ve seen a lot of sleep data from people out there
Suggesting something’s going on. So it needs to be kind of studied and also stress so
And we’ve already have several publications on this and another one that we recently submitted
Showing using an elevated plus maze which is used by pharmaceutical companies to evaluate
Anti stress or
Evaluate the fear response in in rodent models. We noticed early on that
It was easier to handle rats and mice that were in a state of ketosis. They didn’t have this fear response
They weren’t trying to bite you
So if you use in elevated plus maze where a rat kind of goes out on a catwalk
And they don’t like Heights they don’t like that
they can they can stay out in the open arm or they can go into the closed arm where it’s safe and
rats have a natural tendency to explore that’s and humans have a natural tendency to explore so when they’re in the state of
Nutritional ketosis they stay in the open arm
I think about 25 to 30 percent more and they explore their environment
The novel environment whether so that’s the implication there for humans. It’s for people who have like PTSD
Maybe like social anxiety and things like that. We think especially for PTSD
We think that being in a state of nutritional ketosis helps
Balance the neuropharmacology of the brain by it. Does this by elevating gaba to glutamate ratio by activating?
glutamic acid decarboxylase
AG add
65 and 67 enzymes so you don’t have to know all that but it changes the neuropharmacology of the brain
To make you more relaxed. It’s actually hitting things and
Receptors that actually may be hit, you know in a more abrupt fashion with alcohol, but it’s doing it, you know
Naturally, it’s you know, more GABAergic activity is a more, you know brain stabilizing calming activity
And we’re also looking at the adenosine receptor insert to nergic systems
but the thing that jumps out and why it may have an anti seizure effect is that you are
Taking a potentially hyper excitable
Neurotransmitter that’s actually could be
Neurotoxic in the context of traumatic brain injury PTSD and seizures. That would be glutamate
So glutamate is converted to gaba through an enzyme called glutamic acid decarboxylase
Ketosis activates that enzyme so convert more of this stress, you know anxiety
hyperactivity
neurotransmitter to a more brain stabilizing calming neurotransmitter
So that’s firmly worked out and we’re working out the details as to you know
What exactly what receptors or overlap with certain area kadena synergic and all these other things?
So we’re working out that pharmacology
So from a warfighter perspective from an astronaut perspective, you know the energy density, you know
Takes ten twenty thousand dollars per pound to get something up in space
satiety factor anti catabolic factor
Sleep and stress and we’re also now
We can’t really talk about it, but we are doing studies now looking at physical performance and cognitive
performance
From my perspective i’m interested in physical and cognitive especially cognitive performance in
The context of extreme environments so you can do this task
At one atmosphere of pressure right some you know reaction time or critical thinking
Tasks and there’s different tests that we use for that
Can you go to?
You know
18,000 feet and do the same task
Or 20,000 feet or whatever
hypoxic
There’s a very predictable
You know impairment that will be you know, conferred upon the person or you know to following this
cognitive function tasks
Can we preserve that under under extreme environments under the in the undersea environment as it pertains to nitrogen narcosis?
high pressure nervous system
Activity things like that. So that’s kind of what we’re doing now in rodent models
I mean, we will look at the activity under ambient conditions
But we also put them into these extreme
Environments and see if we can preserve you know
Make them more resilient in that environment and we’re vetting out
Various types of strategies to induce nutritional ketosis and finding out what can rapidly go to the field
so as far as you know tolerability safety safety is probably the one and
You know
Is it something I can put in a container or put in a little 5-hour energy size?
Thing and have a couple hundred calories where I can consume that and that will give my body
A superior alternative form of energy that has a host of other
Things and it’s likely not going to be a single agent, but it’s likely going to be a formula
So now we’re working with different formulas
It’s encouraging that a single agent can have a profound effect
But we think that the real, you know, the greater effect can be when you start mixing these things together and adding some cofactors
But we’re very encouraged by just a single agent has outperformed all the drugs
That we’ve you know that have ever been tried for anesthesia
So we’re you you were probably going to take that agent and combine it with various other things
To make it more tolerable palatable and more efficacious
yeah, the the
Possibilities of the ketogenic diet in a pill or a shot or something like that are huge
In I was skeptical. I was pretty skeptical in the beginning but the military actually
Wanted something that can be consumed just prior to admission and you know
And they’re looking at they didn’t want to do the high fat diet
Now our views have changed of the high fat diet over the last ten years so that could be revisited
But they really wanted to it wasn’t my sort of decision on this. They really wanted a
Key, they wanted to induce therapeutic level ketosis
independent of dietary restriction that
Was that was what was told to me? And I was like, how am I gonna do that?
So I saw that NIH was working that Oxford was working. So I visited, you know those places and met with scientists one of them
Dr. Richard Veatch, he was the
graduate student of Hans Krebs and so one of his best students
He’s at the NIH and was actually funded by DARPA with a lot of money to develop a ketone ester for warfighter performance
So so we, you know tested that compound and instead of just focusing on one compound which most labs
do you know we study everything and find out what works and we throw away what doesn’t work and then we focus on
developing novel compound
you know testing what’s already out there, but also
Developing new compounds that are more powerful more dense and more
Have greater ability to be consumed and tolerated
So we’re at that now some of the things are highly
Palatable and tolerable but they tend to be the
sort of
You know less potent agents. So the potency of a compound is almost inversely proportional to its
Tolerability so as these ketone esters as you have like a mono ester
Diester or try a stir and in different compounds they tend to get increasingly more
Aversive in taste and tolerability so we are working on
That’s why formulating is very very important to us
And we’re doing that in rats now. And and also I test things on myself too sometimes so
Anyone experiments you’re famous
Yeah, yeah
So thinking from the perspective of your day to day guy in the Navy
Who wants who sees all these potential benefits who sees the idea of you know?
I’m going on the ship and I’d love to be able to
You know if I have to go a while without food to maintain
performance
to get that deep sleep even if I’m not gonna get a lot of sleep all these things that you’re talking about and now a
Lot of the folks that I work with they fly in a particular aircraft that just got aerial refueling capabilities
So now their missions go from four hours to eight hours in plane. We have you know, no coffeemaker. No microwave. Nothing like that
Yeah, how can a normal person?
Take this kind of stuff that we have right now the technology we have right now
Into a shipboard environment and you can get these benefits
So I’ll approach it first from the perspective of
diet and
from time restricted eating
Protocol, right so intermittent fasting that’s a big thing. Right? I like to call it time restricted eating, right?
So I talked about when you fast or do the ketogenic diet and then you go off the diet and then go back into
fasting again you were you would adapt much quicker to
Fasting you could preserve your cognitive and physical performance, you know, because your body starts making ketones faster
so I would suggest that guys do not that’s not the ketogenic diet, but do intermittent fasting a
Good protocol, which I think is, you know, six six hours of eating in 18 hours of fasting
So for me today is a day. I’m intermittent fasting. I will start eating
Maybe at about 3 p.m. And I will finish eating. I’ll have a nighttime snack at 9 p.m
Right, it will be my last meal and I basically just skip breakfast and I’ll skip lunch sometimes I start at like 1:00 p.m
And finish at like 7 p.m
And that’s six hours of eating and now typically maybe two meals and maybe a snack and then that 18 hours of fasting
Does put us in a mild state of ketosis, even if we’re not like, you know on a ketogenic diet
but if you do low-carb or if you eat ketogenic
During that eating window, then you you’re kind of always getting some of the benefits of ketosis when you start eating again
You still maintain?
You know a mild state of ketosis and then you get sort of the benefits of fasting
So that cokes is your body into being what we call fat and keto adapted
So if you take that individual and you take away and you have limited food availability in an austere
environment that individual will have better access to
Her his brain will be his or her brain will be more resilient to hypoglycemia
And also have a greater capacity to liberate
Fatty acids from adipose to preserve their energy cognitive physical performance
Under high energy demands so that that’s sort of the advantage right there
So so that’s that’s like low tech right? That’s like, you know
Your macronutrient ratios and time restricted eating and then you have exogenous ketones supplementation, right?
So this could be something that’s in like a little
5-hour energy kind of thing and it’s a very
energy dense formula perhaps of ketogenic fats and
exogenous ketone
mineral ketones which could be beta-hydroxybutyrate
Attached to sodium potassium calcium magnesium, which is a salt
So it gives your body minerals and then there’s different esters that could be
Utilized and there’s a whole toolbox of esters that we’re studying right now. The important thing is that
You know
You could drop guys off for five or six days into an area and let them do their mission and they could carry on their
bodies
You know various
Small vials of this stuff and be able to consume it and it could be formulated in a way to give them
Not only a burst of energy but sustained energy over
a fairly significant
Period of time if they were to get a blast injury traumatic brain injury or if they were going to do an oxygen rebreather dive
if they’re going to hypoxia, like they they would potentially have neuroprotection under all those different circumstances and
May be able to maintain cognitive resilience a little bit better – under those circumstances
So these are things that we are doing in animal models that we want to do in human studies
So the trick with human studies is finding the optimal formula that they can tolerate the dosing the individual, you know
and it takes
You know rats you have an inbred strain a rat and they’re all kind of the same
And the data looks great and they have humans and this guy is eating, you know, basically
I don’t know monsters and and you know sugary drinks and Snickers bars and another guys already doing paleo as he you know
He may respond differently. So we really need to
Get funding to be able to do this in a very controlled environment
Because the payoff could be pretty big as far as warfighter performance
It’ll probably start in the Special Operations community and maybe work its way down
With the idea, is that you have
This as a tool in the toolbox, you know
I’m not all about
Replacing what the military is going to eat as far as their nutrition because that’s not going to happen
but to let them know that a key to jet or low carb eating strategy is a strategy that may have these benefits and
And to make it available for those guys who want to do
You know
Knowing what we know now
the rodent date is very compelling and the stuff that we’re doing now is very compelling and it’s already moved to
human studies that are ongoing
So I see a lot of potential there is using new troop nutrition as a
Performance not only as a performance enhancer
But something that can enhance the safety – that’s the primary objective the safety but out of those safety studies
Also led us down paths where we’re looking at performance and performance resilience
So there’s different ways to do it. Like I could talk about, you know different types of formulas for exogenous ketone formulas
But I think we’re a little bit too early yet in describing the ingredients in those formulas, you know
We’re in the basic science concept of that but time restricted eating low carb
ketogenic diet exogenous ketones maybe all in combination – right
So maybe not to do one or the other but these things likely have either additive or synergistic effects when you use together
yeah, so many tools in the toolbox like you said and
For people who are in general. Just trying to see what works for them. And what doesn’t
you’re you’re famous for these nf1 experiments where you you’re testing yourself you’re pushing your limits and
Now so many people are wearing monitoring devices. They have access to lots of data
What a nice would you have to people who want to experiment and to see what’s?
Optimal for them and maybe could you also tell the story of your seven-day fast and the deadlifting?
Yeah that gets round
Tim Ferriss Mitch, I didn’t know he was going to mention that on the podcast
But I guess Peter Atia told him told them about the story
so
Okay, so monitoring. So right. So what what can the person out there listening right now do they can go to their local?
CVS Walgreens drugstore
Amazon and buy a glucose and ketone monitoring system
Right and they can simply it would be good to know
Their glucose response to a meal that’s very important from a health perspective
You don’t want to be you don’t want to have glucose excursions up to like 200 milligrams per now, you know
You want to stay, you know under one?
so I
Would say try intermittent fasting perhaps the time restricted eating protocol with low carbohydrate diet. Perhaps starting
100 grams or less per day and then working down to 50 and
over a period of time you can check your blood ketone levels and once you’re above
0.5. You are clinically in a state of ketosis and
for a diabetic a type 1 diabetic
Person who’s not on occasion a diet that could be dangerous but for us that that’s a good thing
So diabetic ketoacidosis is very very different and then nutritional ketosis and my PhD student
And ruku, t’nuk did a TEDx talk
That you can look up which talks about that subject a type 1 diabetic using nutritional ketosis to manage his disorder
So that’s all say about that, but I get a lot of questions about type 1 diabetes
So I just you know
refer to Andrews TEDx talk
So for nutritional ketosis you want to be 0.5 or above ideally around two one to two million more range
Check your ketones
Typically later in the day when you’ve had some some ketogenic meals in you or you’re fasting and see how you feel
and also maybe when you’re not measuring
See how you feel subjectively when you have the most energy when you have the most lucidity and mental mental
Resilience I guess you could say I when I get into these phases
I’ll do a lot of writing or a lot of
sort of tasks that require a lot of you know cognitive and I will
Tend to check my my glucose and ketones and I typically find
That my ketones are in like the one to two and maybe upwards to the three range and some people I know
Actually get much higher
there’s people in the lab that are like running four or five and
Other people that are on a strictly to genic diet and can barely even make it to that 1 millimolar range
So everybody is going to be a little bit different
so by a meter online
They’re relatively cheap under 50 bucks the strips
If you search around you can get them for anywhere between $1 to $2 a strip and and get some some data on yourself
Experimenting yourself and then from there you can start
You eating other things? So I use an aura sleep ring and for sleep and the aura ring?
Monitors a number of different factors most importantly for me
It’s a pretty good measurement of your sleep time and sleep architecture like how much you know
Delta sleep. You’re getting and REM sleep and things and
And I we use this for our NASA extreme environment Mission Operations sort of mission to on the crew members
So it’s a very Hardy technology. I mean you can train with it and it’d be hard to break it actually
So monitoring your sleep with a Fitbit or an aura ring measuring your glucose and ketone levels
I think is a good place to start right and then we all have certain things
Like I know my strengths
I keep a training Journal or used to keep you know
Very detailed records of training Journal and then you could whether you’re a runner or a cyclist or whatever, you know
Start monitoring this get your baseline
initiate the ketogenic diet or
exogenous ketones or intermittent fasting whatever you want to do and
Monitor your blood ketone levels and then assess those
Things that you’re interested in, you know
Your performance times not just subjectively but objectively
Right and monitor your sleep because your sleep will be a factor in those, you know
performance to get general blood work CBC CMP
You know do get a lot of baseline data because it’s going to be important I think for me
I never thought I would continue with the diet. I was just doing it from an intellectual perspective and that I wanted to understand
what it felt like for my brain to run off a different energy source, so I became obsessed with this about 10 years ago and
and I was very inspired by the work of George Cahill at Harvard Medical School where he fasted subjects for 40 days and
and was able to add some conversations with
Dr. Cahill, he passed away in
2012 and a lot of the icons are up in their 80s and 90s pushing a hundred Allen many of them are still alive
they did go on to to live extremely productive lives and
contributed massively
To metabolic physiology, which don’t have the metabolic physiologists nowadays that we had back in the day
But I was really inspired by his work and actually wanted to fast for seven days not 40 days
So I did
Quite a lot of blood work before during and after and was able to get my blood glucose down
To a level that was significantly below my ketone levels
So my ketones were at at the end stage about double what my blood glucose was and because ketones can readily cross the blood-brain barrier
We can say that
Roughly two-thirds of my brain energy was being run off ketones and during that time
I actually worked on a lot of grants and was very productive and actually getting got funding off one of the big grants
I worked on during that time. I was teaching and even at the end of it
I went to the gym and tested my strength and found that like my strength did go down a little bit
But I didn’t push myself too hard because I knew you know, I was thinking I’m fragile. I just wanted to be kind of
cautious as to
Moving weight under that kind of condition, but I did find
Which was really interesting to me that my strength did not take a big hit
And I was semi keto adapted because for about a half a year to a year or so
I had been tinkering with the ketogenic diet the clinical ketogenic diet and it really made fasting pretty easy the third day
I was kind of hurting but after seven days, I mean I was lucid enough to be sharp and give lectures and
And had the energy to move, you know, five six plates on a deadlift, you know
I didn’t ever thought going into this. I would have never I thought, you know after four or five days you’d be so weak
You it’d be hard to stand up
You know that
You’d have and I did have orthostatic hypotension in the beginning I’d stand so I had to get I would have soup broth
But no calories, you know, I’d have sodium and water and fluids and things like that stay hydrated
But I don’t know the static hypotension is that’s when you stand up real quick. And you feel dizzy just for the yeah
That that happened a lot with me in the beginning I get because – yeah, your insulin goes down, right?
So insolence role is sodium reabsorption in the kidneys, right?
So if your your insulin levels down you’re dumping a lot of sodium
So I think in the beginning I was drinking a lot of water but not getting the sodium that I needed and once I started
Getting the sodium in it’s like I started kind of waking out. My blood pressure came back up again
And I remember kind of sodium loading before you know
I had to do a thinking task or work out or something like that, but I would go for like long walks
You know at the time just very easy walks and that my ketone levels would get up I come back and my glucose
would be in a range that the meter wouldn’t even detect it would just say low I would just say low and it wouldn’t even
detect it and
And I tinkered with a few things to get my my glucose down really low
I don’t know exactly how low I got it because the meter wouldn’t wouldn’t register it and then and my ketone is pretty high and
and realized that
This really does make you resilient your body feels kind of Numb in a way like but at the same time your senses are heightened
So I would go for a walk and I could smell things or maybe even see things sharper than I could could otherwise
So now I got the full understanding of when when people fast and they say it brings them to another level
And I think the more you do it the easier it gets and probably the more benefits you derive from it, too
So, I mean you could tell like major things were happening in your body, you know major things are happening like otology
of course like you when you force your brain to go from glucose to
Ketones luckily at the brain is incredibly metabolically flexible and its fuel utilization and then it can make that switch
Not everybody. Can I mean some people may have a harder time than others?
But like I said, the more you do it these your gets and the more benefits you derive from it
And I think it can be a very I mean I did it for scientific sort of reasons, but it’s also sort of a personal
Journey, too. So you learn about a lot about yourself what you can and can’t take you know
How resilient you really are and you think man if I was dropped off?
It got lost or something and had limited food availability, you know, at least I know you know
I could I could get through it and not die after you know, two or three days of not eating
So that was I encourage people to do that, but I don’t make the recommendation I’m not a medical doctor right so not some people
Yeah, no, no, no medical official advice dispensed here
but yeah a general general thing and you talked about how there are these great scientists who inspire you who have
Made a huge contribution and you are someone who is also very active you were on this big journey
You were making contributions left and right. What is it that drives you to keep to keep pushing on all these fronts?
I think there’s a lot of things. You know that drive me my students drive me
I mean seeing their passion for science and and looking back and thinking
you know remembering how fascinated I was for example with the brain like I was
Fascinated like what is a thought like what is that? So I would as a neuroscientists
As a PhD, I did patch-clamp
Electrophysiology, which is kind of sort of a technique where you record directly from neurons and how they communicate to one another
and you delve very
mechanistically into all that so
asking questions and being very curious and
and I think some from some extent there’s a
sort of a selfish if you want to call it that I want to be able to learn and extract information from
the body of knowledge that’s out there but also from my own experience that I could apply to myself and I get so
enthusiastic and even giddy that I want other people around me to
follow it too and family members because you become so aware of the benefits of some of these things even from a new you know,
especially from a nutritional standpoint
Where my emphasis was really on drugs in the beginning and it was kind of more and I’m still do drug research. But this idea
that
Altering your metabolic
Physiology through changing your macro nutrient profile can change fuel utilization
In your body and that can have this host from cognitive
to
anti-inflammatory effects to potentially tumor suppressing effects to anti-seizure effects like that that you can do that that you
have
You know you are empowered to be able to do that just by
You know the food that you eat or the different supplements to that that could potentially be used
So I’m pretty motivated by that and I really feel
Not necessarily the case for everybody but uh because I don’t I don’t think some of the pioneers in this area
necessarily fast it themselves or experimented on themselves, but a lot of them did and I
Feel that you really have to immerse yourself into what you’re doing and almost be part of what you’re doing to really have that enthusiasm
to the point where you’re so excited it’s hard to fall asleep or you wake up and you’re like
Kind of you know, what’s gonna happen today? Like what will this blood work show what will this measurement?
Like how will this day go?
so to be so immersed in your research that it becomes sort of part of who you are and
Part of your envision contribution, right? So you want to
And also guides my research
So a lot of the things that I do on myself or maybe see others do I get a lot of feedback from people too?
That actually guides my research someone will email me about this or that and that has actually guided, you know
Various research projects that we have so every day I wake up and I’m excited. I don’t know what’s going to happen
like I’m usually testing something new on myself my students have
their in the lab now, you know in the trenches doing research I get to come in and they have
You know so much enthusiasm about what they do
so that’s kind of what drives me on a day to day basis and being able to look forward and actually
make contribute to
The scientific body of knowledge to use food as medicine and it doesn’t have to be a macron. It could be like
There’s companies out there that are creating what I call engineered food
Whether it be a cookie or a brownie where they’re not only changing the macronutrient profile
but they’re incorporating different ingredients that make it like a functional food whether it be a prebiotic fiber or probiotics or
An alternative energy substrate. I mean one of the first things I use was
Saito Maxx when I rode my bike, it had alpha L poly lactate in it
Which was sort of that got me interested in alternative fuels and this is going back 15 years ago and creatine monohydrate
you know, I started using that in 1991 or 92 and
Always stayed up on the literature. So I think of ketones is kind of like the next creatine and but a much more versatile
so it can be neuroprotective if it can make your it enhances your body’s ATP production, but it has
A lot of advantages and a utility that something creatine doesn’t have but but mixing them two together
Would be sort of one of the formulas that I’m working on now like, you know putting various
Alternative energy substrates together and cofactors which allow you to use use these things in a in a more enhanced fashion
I would say
so
That’s what’s I mean, that’s an exciting thing and also cancer. I mean a lot of what we do
I didn’t talk about it much what could be more exciting than killing cancer cells?
you know our soldiers go out to war to kill the enemy to protect us and
we we kind of kind of think of my PhD students as
sort of soldiers warriors that are kind of attacking cancer cells with their the therapies that they’re
developing together as a group and
Testing in cells and tissues and animal models and we’re moving it to human clinical trials
so we’re sort of on a war against cancer in a very
Targeted fashion from a metabolic standpoint. Yeah, and and everyone knows someone affected by cancer
So it’s it’s such an absolute a universal cause and and it’s it’s great that we’ve got you on the team
And the people the students many of the people in the lab were motivated from a personal perspective and that’s why they chose
You know their particular projects to that’s often the case. Oh, yeah, I can get that
Yep, don’t want to be respectful of your time before I ask my last question. Where can people find you online
The best place to find me is the website keto nutrition most importantly it’s dot o-r-g
not calm so keto Nutrition dot Oh ROG and
I have a blog there I have
Products that we’ve tested I have resources like doctors consultants
Podcast
That’s my kind of one-stop-shop for
people who want more information about what we do great and
Tell my final question if you were talking to a military leader who wants to create a culture where people have this
Intellectual curiosity that you display this self experimentation this drive
What suggestions you give them? I?
Was talking to a military leader to embrace his culture
I
Would ask that military leader and try to persuade them to do it themselves and to evaluate
Whether they thought personally that this was a viable strategy, you know
So I would do something
as simple as time restricted eating if you have I was locked into a pattern of not only eating like five or six meals a
Day, I would eat like seven or eight meals a day
Wake up in the middle of the night and eat a protein bar or shake and go back because I thought I needed that
so I come from that mentality, but
when you liberate your yourself from these frequent feedings, or
free yourself from it becomes very liberating right when you free yourself from that eating pattern so when it comes to nutrition maybe
You know, we do a lot of different things
but the most simplest
Low-tech thing I can think of is to say hey if you haven’t tried it before it
Maybe try time restricted eating. Don’t do it every day
Maybe just do it like twice a week and see how you feel and the more they do it the easier
It’ll get and then a lot of that great feeling that they have towards the end of the fast that’s actually due to
beta-hydroxybutyrate the ketone body that I study so and that’s conferring many of the
health benefits like anti-inflammatory effects and you know
Epigenetic effects and things like that. So that’s good. That may be a gateway to get them into
experimenting with an eating paradigm that
without question has major logistical
Practical advantages to guys in the field from a physical cognitive and maybe even anti-anxiety
Perspective and we know you know if you’re edgy and you’re jacked up on caffeine and edgy
So, you know I go to the range. I shoot quite often and I experiment on things, you know
I don’t I don’t talk about those things on podcast usually, but but not only the gym
But I’ll go to the range and I’ll evaluate what gets me better scores on my shooting tests
Right, and I could tell you that the things that I talked about and things that I mentioned
Start doing it and start
if you go to the range start recording you were your scores and you’re gonna see that too and that’s you know something I
Never really talked about but I think from their perspective is a very practical
Benefit to that. So the worst thing to do for a soldier that has
A gun shooting is to be sleep deprived and jacked up on caffeine
so and I’ve actually been in that situation where I have
evaluated my shooting ability under those conditions and I was all over the place but
Being on Jack jacked up on caffeine it gives you the confidence
You actually think you’re shooting well until you actually it gives you like a false confidence
but but when you’re in a state of fasting ketosis or nutritional ketosis and you’ve maintained that I
guarantee not only physical cognitive performance
but things like things are very important your decision-making and shooting performance will will improve
So I would say give it a try but they kind of for me I can read all the studies in the world
But I needed to actually experience it myself
To have the belief and that belief through self experimentation led to a further
Enthusiasm to pursue this path as my career. So over the last ten years. That’s why I’ve been doing
Dumb, thank you so much