Dr. Volek & Dr. Phinney – Translating the Basic Science of Nutritional Ketosis & Keto-Adaptation

Dr. Volek & Dr. Phinney – Translating the Basic Science of Nutritional Ketosis & Keto-Adaptation

July 28, 2019 18 By William Morgan


– So, I am dual mode in this next session.
I’m gonna to introduce the
first of a pair of speakers
who have been working together
for the last 15 years or so,
and that’s Jeff Volek and myself;
and just to give you a 30 second
sense of how we met,
our first meeting occurred when
Jeff crashed a CME course in
San Diego; he’d managed to sneak in
and sat down next to a guy
in the back row and said,
“Do you know who Steve Phinney is,”
“since he’s supposed to speak soon?”
and I said, “Yeah, that’s me.”
(audience laughs)
I don’t remember that that was Jeff;
I just remember the incident
because after I gave my talk,
he and another guy, who both
of them at that point were
competitive power lifters,
got me in a corner
and asked me a bunch of questions,
and that was 1996, I think.
But in 2003, Jeff and I
reconnected at a nutrition
conference in San Francisco.
I walked by a poster that had
work on the ketogenic diet
and body composition
in males with metabolic syndrome;
and I looked at that and
said, “Wow, that’s amazing,”
and then I noticed that it
referenced a couple of my papers
from back when the
dinosaurs walked the earth,
and I met the co-author,
and the relationship for
the last 15 years has been,
for me, kind of a career resuscitation,
and just a true gift.
So, what I want to do is
introduce Jeff at this point.
As you know, he’s a professor
here at Ohio State University,
and an international expert in the topic;
and we will be talking about the emerging
science of nutritional ketosis.
(audience applause)
– Okay, that was just really
an excellent talk, John,
and it kind of struck me that
this tool of a ketogenic diet,
from a therapeutic perspective,
it’s really the opposite
of how you think of drugs
being developed where you start
with the chemistry, you
know what the formula is,
and you know what the target
is, and you do animal studies,
and you take it into various
phases of human trials,
and we’re kind of doing the
opposite here ketogenic diets.
I mean we know they work in humans.
We’ve known for a long time
they work to treat seizures
and even diabetes, and now
we’re back-filling that with
some of the molecular mechanisms,
so it’s just fantastic
work you’re doing.
It’s a lot of still important questions
to address related to
how we wield this tool,
and how it works, but we
know it works in many ways.
So, I put this historic slide together
just to emphasize the
point that in many ways,
from my perspective anyway,
we’ve been living in the dark
ages when it comes to our
diet policy and nutrition,
and we’re ignoring a
lot of relevant science;
but in particular, if we
look at the metabolite,
ketones as a metabolite,
they’ve been maligned
more than any other metabolite
that I can think of,
and this is really unfortunate.
If you go back, and on
the top here I’ve kind of
got a lot of the negative
factors that have contributed
to this connotation of
ketones being negative;
it really started with their discovery.
They were discovered back in the middle
of the 19th century in the
urine of uncontrolled diabetics,
and that negative connotation
has really stuck as labeling these
as a harbinger for metabolic problems.
And then, you know, you
kind of fast-forward.
Insulin was discovered in 1920s
by Frederick Banting,
and prior to that time ketogenic
diets were actually used
to treat diabetics; but with
the discovery of insulin,
and this was a life-saving
discovery, it’s super important,
but it also allowed us to
continue what at the time was
we started to embrace
agricultural carbohydrates,
and then of course you have
Ancel Keys coming on the scene
with a diet-heart
hypothesis further promoting
low fat, high carbohydrate diets
which led to the first US
Dietary Guidelines in 1980,
followed by the surge
in obesity and diabetes,
and we’re still fighting this
negative perception around
ketones, which are
fat-derived metabolites.
But what’s going on in
the bottom of this slide
are a lot of positive things.
So, you can go back pretty
far in history and read about
the use of ketogenic diets.
You have William Banting,
a different Banting,
writing Letter of Corpulence
back around the same time
the ketones were discovered,
and you do have ketogenic diets
being successfully used by a
lot of physicians to manage
both diabetes and epilepsy back
in the early part
of the 20th century.
You have Stefansson’s work,
which I think Steve’s gonna
to talk a little bit more about;
he literally locked himself
up and consumed a ketogenic diet
to prove that it wasn’t harmful.
But notably, you have George
Cahill’s pioneering studies
at Harvard throughout the
’60s and the ’70s really
documenting the underlying
metabolism and physiology
of ketones during starvation.
I still go back and read
these papers in the ’60s;
they were just elegant
experiments documenting how
starvation ketosis plays
out physiologically.
And you’ve got Dr. Atkins
coming on the scene in the ’70s
who popularized the Atkins Diet,
which is still very prominent
today, and we’re fortunate
to have Atkins as a sponsor here.
So, if you look throughout most
of the ’70s, ’80s and ’90s,
there’s very little research
done on ketogenic diets;
it was a toxic topic to be involved with,
with one notable exception,
and that’s Steven Phinney’s work.
So, he published some really
seminal work on keto adaptation
and ketogenic diets in the ’80s;
and I think these, for me,
these were just like reading
word out of the gospel.
I mean these were studies that existed
when no other people were doing studies;
and so that really inspired me to think
that I was thinking along
the right direction,
and I started to do work in the late ’90s,
and I think several other people
started to do work as well,
including Eric Westman,
and it’s just grown from that time to now.
Over the last 15 years, I
would say we’re entering
the golden age of ketones
where we have all these
new discoveries, which
we’ll hear about today,
on mechanisms of ketones,
oN applications of ketogenic diets.
So, welcome to the golden age of ketones.
(audience applause)
I just want to mention briefly
what my team does here at OSU.
I’m really fortunate to
have an incredible group of
doctoral students, master’s
students, undergraduates
and other team players
that contribute to a really
exciting environment where
we’re trying to advance
the knowledge and application
of ketogenic diets.
Fundamental to what we
do is feeding studies,
so we’ve established
infrastructure for doing controlled
feeding studies, ketogenic
studies, and trying to apply
that in as many different populations,
ranging from clinical work,
a big focus on cancer,
and you’ll hear Parker
Hyde talk Friday morning;
but we’re also studying, at
the other end of the spectrum,
military performance, and how
we can enhance the soldiers’
health and readiness and
resilience and performance;
and a lot of underlying
physiology, including muscle
adapatations, cardiac adaptations, etc.
So, we have I think about
a half a dozen posters
on display that my students
will be standing next to,
this afternoon or this
evening at our poster session,
that’ll give you a little
snapshot of some of the work
that we’re currently involved with.
So, I wanted to just
introduce a couple terms;
and you’ve heard these before,
but I think it’s worth emphasizing.
When we talk about ketosis,
understanding concentration
is really fundamental.
If you’re eating a normal mixed diet,
your ketones are suppressed.
So, your concentration of
ketones in your circulating blood
is for most people under .2 millimolar.
When you restrict
carbohydrates for most people,
under 50 grams a day,
you normalize ketones into the range
of nutritional ketosis, which
we’ve sort of arbitrarily
defined as between .5 and up to 3-4;
occasionally, you can transiently get
a little higher than that.
So, that’s an entire order
of magnitude higher than
you would have in the carb
fed state, but an entire
order of magnitude lower than
what you see in ketoacidosis.
So, you’ve got, really …
you could suppress ketones
down to .01 millimolar,
all the way up to 10
millimolar in ketoacidosis:
that’s three orders of
magnitude different in this
particular metabolite;
and when we’re eating
a ketogenic diet that’s well formulated,
you’re simply normalizing
ketones into this range of
nutritional ketosis where
we’re increasingly learning
we have broad-spectrum health benefits;
and when you do that over
a sustained period of time,
that really encompasses what the term
“keto-adaptation” means,
and we’re just scratching
the surface on understanding
the various ways in which
tissues and organs adapt to
being in sustained ketosis;
but fundamentally,
you’re enhancing reliance
on fatty acid oxidation and ketosis,
and we’ve documented this
in different populations.
You basically double your
rate of fat oxidation
when you’re in ketosis.
It’s true if you’re a type
2 diabetic with insulin
resistance, or if you’re an
elite ultra-endurance athlete:
the absolute numbers are
different, but relatively speaking
you double your rate of fat
burning, and that I think is
important for a variety of reasons.
So, keto-adaptation is really
a perfectly natural process
that, as humans, we have evolved
to have this very elegant
sophisticated system of being
able to not just survive,
but thrive, in the context
of very little carbohydrate;
and you could argue, from
an evolutionary perspective,
at least intermittent ketosis
was the normal state before
the agricultural revolution,
which started maybe 10,000 years ago,
and that’s less than 2% of human history.
So, I just very briefly want
to show you a little bit
of data from experiments
we’ve done over the years,
and we’ve done a lot
of perspective studies;
this is just one in particular
in people with metabolic
syndrome or prediabetes.
So, these were individuals
randomized to either
a low carbohydrate or a ketogenic diet;
and right off the bat,
we see people randomized
to a ketogenic diet lose more
weight without specifically
instructing them to restrict
calories, so these are
ad libbed on ketogenic diets;
and we see this time and
time again that obese people,
that follow a well-formulated
ketogenic diet, don’t need
to count calories, that they
naturally restrict energy.
You can see the individual
responses on the right where
the average weight loss in
the ketogenic group is higher
than any individual
person on a low fat diet.
And we’ve done a lot
of work characterizing
the insulin-resistant
phenotype, if you will,
around responses to ketogenic
diets, especially around
dyslipidemia, and we see that
cholesterol profiles improve.
There’s nothing more potent
than a ketogenic diet
to lower triglycerides, and
it also consistently raises
HDL cholesterol and improves
the particle distribution,
you’ll hear from Ron Krauss later today,
but it does have a variable
response on the LDL
cholesterol concentration;
but independent of that,
you consistently see decreases
in the small LDL particles,
and there’s increasing evidence that
they are the most atherogenic
particles circulating.
We see improvements in glucose and insulin
and measures of insulin sensitivity,
as well as improvements
in hormone sensitivity.
So, we see improvements in
greater decreases in leptin.
We’ve also done similar
work with thyroid hormones,
yet we see no change in the
function of these hormones;
so no signs or symptoms of
hypothyroidism, for example,
even though T3 is dropping,
so that leads us to believe
that we’re enhancing
sensitivity to these hormones
perhaps at the receptor
level and signaling level.
We’ve also measured saturated fat levels
in many studies now, not just
this study, and a consistent
finding is that despite
consuming two to three,
sometimes even four times
as much saturated fat
on a ketogenic diet, that
levels in the blood actually
go down or stay the same;
and this has led us to the concept
that you are not what you eat,
you are what you save from what you eat,
and this kind of piggy-backs off on
enhanced fat oxidation.
When you’re eating saturated
fat on a ketogenic diet,
you’re promptly oxidizing
that incoming saturated fat
and converting it to C02 and water.
Saturated fat is, in fact,
a preferred fuel when you’re
in ketosis, and this is very
important because elevated
levels of saturated fat in the
circulation and in membranes
is consistently associated
with higher risk
for heart disease, diabetes,
even some types of cancer.
And you heard from John that there were
some anti-inflammatory effects
in animals who had ketogenic diets;
we see the same consistent
effect in humans trials.
So, half the inflammatory
markers we measured in this
experiment were significantly
decreased in a group
fed a ketogenic diet
compared to a low-fat diet,
and we’re seeing this in
some of our ongoing trials,
including patients with type
2 diabetes, that there’s a
potent inflammatory mechanism,
and you’ll hear from
Dom D’Agostino after this talk
about some of the mechanisms
that may be at play here.
So, what we’ve learned over
many studies now over many years
is that a ketogenic diet
essentially reverses all the
signs and symptoms of
metabolic syndrome in this
insulin-resistant phenotype,
and it’s led me to kind of
view this on a continuum
where the more carbs you eat,
the more you have a higher
likelihood of developing
the insulin-resistant phenotype;
and if that progresses, type 2 diabetes.
The more you restrict
carbohydrates, especially down to
levels that induce ketosis,
the more you express this
keto-adaptive phenotype, which
is a non-diabetic phenotype,
and it’s driven by carbs in the diet.
Everybody has a slightly
different carb tolerance,
and it changes over the lifespan,
and perhaps other other
environmental factors,
but this relationship between
carbs and manifestation
of insulin-resistant phenotype
versus keto-adaptive phenotype holds true.
So, I thought it would be
important, because I’m not sure
it will be addressed by other speakers,
to talk about the idea of
a well-formulated ketogenic diet.
I really appreciate John mentioning
some of the nuances around
optimizing the diet for the animals,
and it’s certainly very
relevant for the human as well,
and we have some understanding
of how to best formulate
and implement the diet to
maximize safety, effectiveness,
pleasure and satisfaction with the diet,
and most importantly sustainability;
and so on that note I will just say
the diet’s anything
from a burden or sacrifice,
from my perspective,
and I think many of you in the
room would concur that it’s,
in fact, a very pleasurable
way to eat and enjoy food.
But I’m gonna to invite Steve to the stage
to expand on that a bit,
and talk to you about some
of the characteristics
of a well-formulated ketogenic diet.
– So, one of the concepts that
Jeff and I wanted to do was
mix in not just the elegant
basic science and mechanisms
here and pathways, but also
to provide some guidance into
how this translates into something
useful in the real world,
and you’ll hear a number of
presentations on different
disease states and such; but
what I wanted to deal with
is something I struggled
with for a number of decades,
and that is, okay, we
can do this in the lab,
we can do it in the metabolic ward:
what happens when we take
this out in the real world?
And one of the first places is to define.
We use this term,
“well-formulated ketogenic diet,”
but what is that?
What are the confines of that?
And probably the best
visual representation
we’ve come up with is to
differentiate this from the
standard American diet,
what the average American
and most people in the developed
world eat, but a better
rendition of that health-wise
is moving to a Mediterranean
diet with less carbs, a
different mix of fats;
and then there is the paleo diet
based on our understanding
of what our distant ancestors
ate, and so that takes the
evolutionary perspective of
what our genes over the last
two million years exposed
to, and that’s thought to be
higher in protein, lower in
carbohydrate, and it’s typically
called low-carb, but it’s
still in the 20-30% range.
So, I really thank Professor
Ramsay to put some of his mice
onto a mouse paleo diet and
look of the effects on that,
and there are some benefits;
but at least in the mouse model,
there is a very significant
distinction between a higher
protein and significant carb
level, which will keep ketones under .3,
fasting ketones under .3
millimolar, in most humans
unless they’re doing high-intensity,
high-volume exercise.
So, to achieve nutritional ketosis
really provides this narrow island;
we think of it as an island of safety.
Typically, it’s under 10%
of daily energy intake
relative to one’s daily expenditure.
So, here we’re not talking
about macros in terms of what’s
on your plate; but if you’re
burning 2000 calories a day,
you have to get under,
typically under, 10% of that,
which would be about 50 grams of carbs
to be on this island of safety.
And again, if you take your
protein intake too high,
that protein intake begins
to suppress ketogenesis.
So, it has to be a moderate protein,
very low but not zero carbohydrate intake.
Then, if you do the math on
that, if it’s 10% or less carbs,
and it’s 20% or less
protein, it’s oh my gosh;
what your body has to burn each day
is more than 80% of this energy as fat,
and that’s really daunting.
How do we do that?
Jeff showed you some pictures,
and that’s compatible with
a well-formulated ketogenic diet.
So, how does one do that?
Thinking again in terms of about
a 2000 calorie per day intake,
and again we don’t specify
calories; it’s just that the fat
is eaten to satiety, we’ll
let the natural highly
evolved human instincts, is
when you take the carbs down,
get that insulin signaling down,
let natural instincts drive fat intake;
but if we restrict carbs to anywhere
from the 25 or 30 grams
per day total intake,
up to 50 or so, what can you have?
And you can see that, recognize,
that there is some
carbohydrate in protein foods.
You know, when an animal is slaughtered,
there’s glycogen in the muscle,
and that’s bioavailable carbohydrate,
but it’s a small amount.
So, if you’re eating a
moderate protein intake,
that protein-based carbs
might be 5-10 grams per day;
and if you eat 3-5 servings
of non-starchy vegetables per
day, depending on your choices
that puts you in the 10-15 gram range.
If you give people 1-2 ounces
of nuts and seeds per day,
that’s again 5-10 grams.
At the higher end, from
20 up to 50 grams per day,
if you give people 4 ounces
of berry fruit per day,
that’s again a 5-10 gram
of carbohydrate intake.
Then, there’s things in
sauces, and such as that.
So, you can see that one can
stay in the 30-50 gram range
and have a range of choices;
and again, from the pictures
here, realize that there are
quite a bit of protein-containing
foods here and there,
and cheeses, but the vast
majority of the calories
here are coming from fat.
It doesn’t mean that the
person has to eat all their
daily energy need as fat,
because we again let their
instincts dictate what their intake is,
and they can choose from a wide range
of luscious foods and condiments.
So, when we say, “Well, we take
away more of your starches,”
“and we take away much of the
sweets that we typically eat,”
“but we give you savory
and we give you unctuous,”
it’s a trade-off.
We also give people who have
severe metabolic impairments,
such as type 2 diabetes,
metabolic syndrome,
and other inflammatory-based
diseases, we also give them
not just a technical
improvement in metabolic health,
but we give them a subjective response.
Again, when somebody’s
with type 2 diabetes
who’s taking 100 units of insulin a day,
gets off 100 of insulin during the day,
that’s a very tangible
perceived benefit, and we can do
that when we get the composition right
and we individualize it
to the metabolic needs
of each person, rather than
having a single formula
cookie-cutter approach.
So, this is variable, individualized;
but again, the key here is
keeping protein moderate
and carbohydrate restricted.
So, one of the questions
that I’m frequently asked is,
“So, what macro should I be
eating?” and I always push back
and say, “Well, we don’t do macros.”
We define carbohydrate on an
individual tolerance basis;
and the best way to
determine your carbohydrate
tolerance, if you want to
be in nutritional ketosis,
is you get a finger stick
glucometer with a ketone testing
and measure your ketones,
and that is now a very robust
and accurate technology, and
now we have multiple vendors
who are coming out with
provenly accurate devices.
So, as Jeff showed you
when he did the study with
Cassandra Forsythe, and took
people with metabolic syndrome
and put them non a
well-formulated ketogenic diet
and they ate to satiety,
initially they under-ate calories.
So, in this what we
call “induction phase,”
if they’re eating 90 grams
of protein and 30 grams of
carbohydrates, that would
be 120 calories of carb
and 360 calories of protein;
and then when they ate that
to satiety, they were
under-eating total calories,
and so the difference
between their expenditure
and their intake was basically
unseen “dietary fat,”
but the dietary fat was
coming from internal reserves;
and as people typically
follow this over many months,
the weight loss continues, but it tapers,
and eventually people will
naturally come to a new
steady state, and that is a combination
of increasing dietary fat,
so their need to meet satiety goes up;
and also if somebody loses
40 pounds, their resting
metabolism is gonna come down somewhat,
and that’s a reality, and that’s a normal
physiological response;
that’s not a toxic effect
from the diet, it’s just
coming from carrying an extra
burden of fat, which has
metabolic requirements both
at rest and during exercise,
and people reach a new steady state.
So, the key here again is
we don’t dictate calories
and we don’t count calories.
We basically rely …
and this is not in
everyone, but in most people
their natural instincts
are to under-consume
through a period of time to
weight loss, and then they reach
what is a new steady state,
and the important point here
is that across these phases
our dietary instruction doesn’t change
from day one ’til the end;
they may increase their
carbohydrate slightly,
if they can maintain ketosis
with a little bit greater
intake of carbohydrate,
which gives them a broader
range of food choices,
in which they can have a
caprese salad with four ounces
of tomato and maybe some
berries at breakfast in the same
day and maintain that
metabolic beneficial state.
So, I want to begin to wrap
up with what Jeff and I have,
working with Dr. Brooke
Bailey who’s in the audience,
have come up with.
How do we define a
well-formulated ketogenic diet?
And we came up with
basically 10 principles,
and these are posted on a blog
post that we put up recently
at our blog at Virta Health;
and the most obvious one is
that, until proven otherwise,
sustained nutritional ketosis,
in humans at least, appears
to have better clinical
response than intermittent
ketosis in terms of degree
of weight loss and improvement in
manifestations of insulin resistance.
So, you know, it seems like
a no brainer, but it’s still
a point of contention,
and there’s still a lot
of work to be done, whether
intermittent ketosis or
continuous ketosis is the most beneficial;
but the greater the degree
of insulin resistance,
our experience is the
better the response will be
if somebody sustains nutritional ketosis.
Next is that it needs to
maintain lean body mass
and function; and again,
you’ve seen that elegantly
in the mouse model that Professor
Ramsay presented to you,
and Jeff has shown that in his research:
that we can take people
on a well-formulated
ketogenic diet, eating to
satiety, not overeating protein,
and yet they either maintain
or increase lean body mass.
So, again, this idea
that it’s a muscle waste,
it has to be a very high protein diet
or you’ll waste muscle, is inaccurate.
Probably the most difficult
one to convince people that it
is important is electrolyte
and mineral management.
We assume that people will
just naturally eat enough
minerals and electrolytes
to maintain their needs;
but when someone enters a
state of nutritional ketosis,
it changes the kidney’s
functioning of sodium,
and that’s been known since the 1950s,
and it’s called the
natriuresis of fasting,
natrium being the Latin term for sodium,
that renal sodium excretion increases
when one is in nutritional ketosis.
But to put it as simply as I can:
if you combine a ketogenic
diet with a sodium restricted
diet in somebody who doesn’t
have obvious need for
sodium restriction, that is
hypertension or congestive
heart failure, you’ll cause a
decrease circulating volume,
and that leads to a
whole panoply of symptoms
and side effects that aren’t
necessary, and those oftentimes
called “the keto flu,”
and that’s not keto flu;
that’s the inadequacy of an
essential nutrient called sodium
to meet physiological needs.
Again, as I’ve emphasized
in the previous slide,
fat needs to provide the majority
of dietary calories in all
phases, and we can discuss,
“What about in the early phase?
Can we cut the fat way back”
“and have people lose more
weight?” and I’m going to
address that in the next slide.
Again, a lot of people
like to count calories,
and if they want to they can,
but we don’t prescribe calories,
and we don’t tell people to purposefully
restrict in those circumstances
because that’s not
something that humans are designed to do
for years and decades, so
most calorie-restricted diets
fail within the first six
months or the first year.
Again, our predilection
is this should be mostly,
or wholly, composed of
whole foods or real foods
that manufactured foods may have
some roles in some circumstances;
but what people are gonna
eat for the duration of
their lifetime is gonna be
predominantly real foods
that are purchased in the normal
pathways of grocery stores,
or you get a box delivered
to your door or whatever;
it should be real food.
Now, here I want to be a
little bit provocative,
but also science-based; and I
will say that in my experience
having done short-term very
low calorie ketogenic diets
for weight loss, not just in
my research but in outpatient
clinical settings, I’ve been
disappointed in terms of
the long-term results;
But again, where you
have people restrict fat
in an artificial way,
they don’t eat to satiety,
but they can use willpower
to use this type of diet to
lose a whole lot of weight;
but when you look at the
results of studies where you
look at one year or beyond, I
have yet to see a place where
a rapid initial very low
calorie ketogenic diet results
in lasting effects in a group of people.
We all know individuals
who have done this,
but show me a group of people.
So, we tried to pull together data
from five published studies,
and the yellow one
at the bottom, the purple
one, and the green one
are all studies that used
formula weight-loss diets
under 1000 calories per
day for roughly the first
3-5 months, and then were
followed up from anywhere
for a year to two years;
and you can see that in all
of these cases, by the
end of the first year
weight regain is beginning;
and then the blue line in there …
I apologize to Dr. Sarah
Hallberg who will be presenting
data from the study she’s
heading up working with us
at Virta Health on reversing
type 2 diabetes …
and this is a case where people
are eating fat to satiety
from day one, that the
weight loss is slower,
but it’s more progressive,
and at the end of year one
we don’t see rebound and weight regain.
So, because a chronic condition,
such as type 2 diabetes,
isn’t going to be cured in
one year, or isn’t going to be
cured in six months, from a
philosophical point-of-view
as a physician, why would
I want to use something
which is only going to
provide transient benefit
to the patient, and then
have them begin to lose
control and gain that weight back?
And so I would say that any ..
if it’s a well-formulated
ketogenic diet, you have
to have demonstrated,
for that condition, that it
will have a lasting benefit
for the average person
for whom it is prescribed.
Again, we picked type 2
diabetes as our primary target,
and we picked it in part
because it’s the hardest one to deal with
because when people have
high insulin levels,
so secondary insulin
resistance, administered insulin
or secretogogs, or insulin
secretogogs, those are the
people who have the hardest
time in achieving the
metabolic changes, and
so we think we are making
progress in meeting
this characteristic of a
well-formulated ketogenic diet.
Then, the last two are when
people are on medications for
hypertension or type 2 diabetes,
many of those have to be
taken away promptly when
the diet is started,
and you have to have
real-time medication management
through the physician and pharmacist,
or nurse and office
staff, in order to avoid
the side effects of too much
medication in the context of
too little carbohydrate
coming in from the outside
and dramatically improving
insulin sensitivity
through metabolic pathways
we have yet to define.
And then the last one, and I
thank Dr. Volek here because
when we came up with this list he said,
“You’ve gotta put it on
number 10,” and that is a
well-formulated ketogenic
diet does not necessarily
adhere to traditional dietary guidelines.
(audience laughs)
Yeah.
You get into conflicts
with a number of guidelines
when you try to maintain
people’s well-being
and function on this type of diet.
So, my next little slide is,
if I can hit the right button here,
the first is, “Do these
provide adequate sodium?”
and as I said, with the
exception of hypertension
or congestive heart failure,
or the other not all
that common conditions
where people have to restrict sodium,
our experience clinically
is we need to provide them
with 5 grams of sodium intake
per day, which is double
our current guidelines
of 2.3 grams per day.
And we have a speaker, Dr.
Andrew Mente, who has published
seminal data in this
obscure journal called,
The New England Journal of Medicine.
(audience laughs)
From the pure study that demonstrates that
for general people,
populations around the world
and different cultures,
the low point in terms of
mortality for measured sodium
excretion, indicating intake,
puts the optimum intake
in the range of about 4
grams per day without people
being in nutritional ketosis;
add nutritional ketosis
and 5 is a modest number.
Again, it’s horrifying,
but particularly when
somebody is in maintenance
for the average,
even a person burning 2000
calories a day, they need to eat
about 150 grams of fat per day,
and the type of fat matters.
That the “healthy” polyunsaturate
fats, which are healthy if
you’re eating a very low
fat diet when you need those
polyunsaturates as essentially fats,
isn’t the same mix of
fats that you should have
when you’re on a
well-formulated ketogenic diet
where most of your fats
coming in are used for fuel,
not for structural
requirement, for membranes,
and eicosanoid production,
and things like that.
So, that means avoiding
the high polyunsaturate
vegetable oils that are
currently in the marketplace;
and the demographics of
that are that are changing.
I’m told that there is
now a significant movement
in the plant sciences area
to move to high monounsaturated
versions of corn and soy,
and it already exists for
sunflower and safflower.
As Jeff emphasized, that if
you’re in nutritional ketosis
and you’ve doubled your
rate of fat oxidation,
it appears that some of the
first fats that get into
the pathway for oxidation
and saturated fats,
in spite of higher intakes,
they don’t build-up
in the blood, and if anything are reduced.
So, again, worrying about
saturated fats is only
associated when you’re combining
them with a significant
proportion of carbohydrates in your diet.
Again, getting adequate
potassium and magnesium
as minerals, as those are
important whether you’re on a
high carb or a low carb
diet; and on a low carb diet,
those come predominantly
from leafy green vegetables,
and to some degree berry fruits;
and if people are so motivated
they can make their own
bone broth, which again is a source
of not just adding sodium to the diet,
but also providing those other nutrients.
Finally, the final point is,
this is not a high protein
diet; and although we have
Bob Atkins to thank for being a pioneer
and a bit of a curmudgeon in
terms of persisting out there,
selling lots of books and
making this a popular point,
he did call it a high-protein diet,
and he’s forgiven for that.
(audience laughs)
But we need to move on.
And the last slide, again,
was a slide that Jeff made.
Do you want to describe
this slide or should I?
So, when I started out in this field,
my goal was, “How do we mobilize fat?”
“How do we get it to be
burned?” and if you mobilize it
in an accelerated rate,
pass it through the liver,
make ketones, and use the
ketones to feed the brain,
I thought, “That’s revolutionary”;
but of course George
Cahill figured this all out
and published it in the 1960s.
What’s happened since
then is we now understand
that ketones are not just a fuel,
and not just for the brain;
they appear to be an optimum
fuel for the heart function,
and now there’s considerable
evidence that, in terms of
gut function, that typically if you eat
dietary fiber and your microbiome
makes it into butyrate,
which is considered to be
an optime fuel for the gut,
that’s easily supplanted
with beta hydroxybutyrate;
and if I make 30 grams of butyrate per day
from 30 grams of dietary
fiber, that’s a lot;
but my liver currently, I’m guessing,
I haven’t checked my meter,
is making between 50-100 grams of
beta hydroxybutyrate a day.
So, again, this is a fuel
for multiple organ systems,
but now we know it’s a signal.
So, you’ve got a molecule
made in one organ,
and it goes to other organs,
has multiple effects,
and so you have to think
of this as a hormone.
This is a very beneficial
regulatory hormone that regulates
the body’s defense
against oxidant distress
and inflammation, which
has an impact on longevity
and lifespan, impact on
inflammatory diseases,
and cell signaling and
mitochondrial function,
including increase in
mitochondrial NAD+ levels.
So, this is a potent
signaling molecule that we are
just scratching the
surface on what it does,
how it functions, and
how do we modulate that,
and how do we modulate it
to the specific needs of individuals.
Thank you very much.
(audience applause)