Dr. Stephen Phinney and Dr. Amy McKenzie on Ketogenic Diets and Diabetes

Dr. Stephen Phinney and Dr. Amy McKenzie on Ketogenic Diets and Diabetes

July 28, 2019 15 By William Morgan


– Welcome to our Facebook Live Q&A today.
I’m doctor Amy McKenzie and
this is doctor Stephen Phinney.
We are researchers here at Virta
and collaborators on quite a few
different research studies together.
Today we’re gonna answer any
questions that you might have
about diabetes, heart health,
ketogenic diet interventions,
anything you can think of.
Please list your comments
and questions below the video
and we’ll get to as many as we can.
– And as we answer questions
today, we want you to remember
that we cannot give
specific medical advise,
so our answers to questions
will be general rather than specific.
And for specific medical questions,
we would refer those to your physician.
– Our first question
today is “How does Virta’s
treatment affect heart health?”
This is a very relevant
question because we just had
a new publication come out today
in Cardiovascular Diabetology
that really focused on this.
So we had published
maybe two months ago now,
we had published the one year
Type II diabetes outcomes.
We showed that A1c improved.
We showed that glycemic
control was better,
insulin resistance was
better, weight improved.
And in this paper we really focused on
all the different risk factors
around cardiovascular disease.
– And that’s important
because in the diabetes paper
published two months
ago in Diabetes Therapy,
we noted that although a whole
group of diabetes-associated
risk factors got better, one
of the more controversial
changes is that the LDL
cholesterol level in our
patient group as a whole rose slightly
but statistically significantly.
We felt it was important
to take a much closer look
at the full range of heart
disease risk factors.
And that is what’s encompassed
in the peer-reviewed paper
that we had published just today
and can be accessed through our website.
– Yeah, so to give kind
of a brief overview
of what we’ve showed in that paper,
Steve mentioned the rise in LDL
and LDLc in the group on average,
but there are a few markers
that some researchers believe
might be a better predictor
of cardiovascular risk
or at least equal to LDLc.
So those are LDL particle
number and apo B.
Those two markers
statistically were unchanged
at one year in our cohort of patients.
And then, we also looked
at the particle size.
Some believe that small,
dense LDL particles
might be more atherogenic
than the larger particles.
And our small dense LDL particle number
actually significantly
decreased at one year.
And the whole, the particle size of all
the LDL particles increased at one year.
So in terms of looking at
the whole picture of risk,
we certainly saw that increase in LDL
that a lot of people get concerned about.
But when you put all
of the markers together
and consider the whole risk profile,
we’re definitely getting an improvement
in a lot of different risk factors.
And we still are concerned about LDL,
but we see a lot of
improvements in other ways.
– Understand that the test
that we use to measure
LDL particle size and
number is a new test,
it’s not universally available.
It’s a predominantly
a research-based test.
And there are a couple of
different ways that these
can be analyzed, and the
medical practice community
has not arrived at a, kind of a uniform
recommendation for these values.
So this is a research test that we did.
And it may not be available
to the average person
through their primary care physician.
For instance, I saw my
physician a few weeks ago
and asked, and I get my health care
through Kaiser Permanente
here in California,
and I asked if they could
run a LDL particle size
and number for me and they
said “no, we don’t do that.”
But, it’s important that other factors
that we did look at,
such as HDL cholesterol,
which is so-called good cholesterol
and triglyceride values,
then those are part of
a standard lipid panel.
When the ratio of HDL to
triglycerides goes up,
that is, you have more HDL
relative, proportionately
to triglyceride, that is
correlated with an improvement
in LDL particle size and number.
So, again, we’ve looked at,
I think we had 18 different
cardiovascular risk factors
in this current paper,
and those were included in that.
So the point is, this
is a very complex area,
it’s an area of active research.
But what we want to provide
is a broader perspective
of all the parameters,
rather than focusing in on what we have
with the cholesterol-diet-heart hypothesis
where the focus for a couple of decades
has been just on the LDL.
The true picture is much
more complex than that
and we want to get into
some of those details.
– Sure. And there’s evidence even to say
that the picture is
more complex from that,
from the Imbarac trial,
because they put people on STLT2s.
They saw LDL go up but they saw
cardiovascular mortality decrease.
– Dramatically, yes.
– 38% I think, maybe.
So, there’s definitely
something to say where
there are other factors at play,
and it’s not all about one lipid marker
in terms of cardiovascular risk.
So we’ll find out someday.
– So before we get into
specific questions,
do we wanna talk about
the range of risk factors?
– Sure.
– That we looked at, responses
such as hypertension, inflammation.
– Yeah. I think also when
we’re talking about different
risk factors and looking
at the whole risk profile,
inflammation is also an
independent risk factor
for cardiovascular disease.
Many consider it or
hypothesize it be an under,
potentially an underlying cause.
So we looked at a few broad
markers of inflammation
in this study, we looked
at high-sensitivity
C-reactive protein and
white blood cell count.
And both of those dramatically improved.
The CRP response especially was pretty
astonishing at one year.
And then blood pressure as well,
blood pressure significantly increased,
and the really cool thing–
– No, it actually decreased.
– Sorry thanks, improved, decreased.
So blood pressure
decreased, so it improved.
And because of this we
actually had to de-prescribe
medications for the
patients because they didn’t
need the medication anymore.
So that’s a really unique finding too.
– So a lot of patients
moved from the hypertension,
borderline hypertension area
to normal blood pressure with a reduced
total medication use in the population.
Which is a very unusual finding,
’cause usually the way
with standard medication
treatment for hypertension
you have to give
more medications to get better control.
– Sure.
– We got better control
because nutritional ketosis
and the Virta treatment that
embraces and supports that
is such a powerful metabolic tool.
– So, that’s a little
bit of a recap on our
cardiovascular risk factor
paper that just came out
today in Cardiovascular Diabetology.
You can go to our website
virtahealth.com/research
and you’ll find a link
to that paper there.
And then we’ll have
certainly more information
coming out from Virta tomorrow about that.
Check back tomorrow and we’ll have
some more information for you.
Our next question, “Is
it okay to eat one to two
“meals per day with half of
your protein needs in each,
“or is it better to
space out your protein?”
– That’s a good question,
and actually kinda leads to the concept
of time restricted eating.
– Yeah.
– We actually did a blog
post a couple months ago
entitled To Fast, or Not to Fast.
And in that we point out that
there is actually a fair amount
of published research on
time restricted eating.
As long as people don’t do total fasting
for more than 24 hours,
certainly skipping one,
or even two meals per day,
when the composition of
those meals is appropriate,
is safe and for some people turns out
to be an effective tool.
And so yes protein doesn’t have to be
eaten in three equal portions,
it can be eaten in two portions.
And there are some people who find
that they eat one meal per day,
so they’re basically fasting,
from basically dinner,
let’s say one evening,
til dinner the next evening,
and that, as long as that is interspersed
with adequate nutrition including
adequate vegetables for
potassium and other minerals,
and fiber on the non restricted days,
it can be a healthy way to follow
a well formed ketogenic diet.
– Sure, protein is important,
so it is important to make
sure that you get it in,
and meet all of your needs.
And then if you,
if you are in a situation
where you’re eating
protein in this way, where
you’re kind of lumping
it all into one meal, and
your ketones don’t go down,
don’t be too surprised.
‘Cause that might also be a factor too.
So depends on what your goals are,
but it is definitely really important
to get in all of your protein.
Next question.
“Is keto safe and, or recommended
if you have no thyroid?
“And is there a risk of low TSH
“if you do keto without a thyroid?”
Doctor?
– Yeah, it’s a good question.
Again we have to be careful not to give
specific medical advice,
but in general terms,
taking thyroid medication
can fully replace what the
thyroid gland normally does.
And it’s important to point
out that the thyroid gland
doesn’t make active thyroid hormones.
It makes a precursor,
called, we just say it’s,
it’s a precursor, it has
four iodine molecules on it.
Active thyroid hormone has three.
The thyroid makes the one with four,
your liver takes away one of those
iodines to make the three.
So you can take the
thyroid hormone by mouth,
and then the liver does the final step,
and can regulate much of that process.
And TSH is a useful test
because that’s a measure
of what the brain perceives in terms
of what the liver’s doing.
And so that can be used by your physician
to help judge the dose of oral
thyroid medicine as prescribed.
So again this is something
that has to be managed
between you and your
primary care physician.
We can’t give you
specific advice for that.
– Great, so if you’re just joining us,
I just wanna welcome you to the
Virta Facebook live Q and A.
I’m Dr. Amy McKenzie.
This is Dr. Stephen Phinney.
We’re here to answer your questions
about diabetes, heart health,
and ketogenic interventions.
If you would like to be notified
of future Facebook lives, or events,
please follow Virta on Facebook.
Our next question is,
“Can being in a state
“of ketosis enhance your
athletic performance?”
I think this is something
near and dear to our hearts.
– Yeah, wow.
Do we have an hour to–
– Yeah, I think we could
spend a lot of time on this.
Our collaborator, Jeff Volek,
that is at Ohio State, and
also a co-founder of Virta,
he actually has been looking
at this a lot lately in his research.
Back at Yukon, a few years ago,
he brought in 10 high carb athletes,
and 10 keto adapted low carb athletes–
– These were elite, ultra runners.
– Yeah, elite, ultra runners,
that do ultra marathons,
or some of them were triathletes.
So it was elite, ultra endurance athletes.
And 10 of them were keto adapted,
and 10 of them were on a high carb diet.
He brought them in to run for three hours.
And looked at all of their performance
during that time, and
then during recovery.
Probably not surprisingly, the low carb,
keto adapted athletes had higher
peak rates of fat oxidation,
and a higher mean rate of fat oxidation
throughout their run.
But the really interesting thing is that,
when it comes to athletic performance,
people seem to be concerned
about muscle glycogen.
And they’re worried that
if your low carbohydrate,
and keto adapted that you’re maybe gonna
run out of muscle glycogen.
Feel like you hit the wall
and not be able to perform.
So they did muscle biopsies in this study.
And what they found was
that the keto adapted,
low carb athletes and
the high carb athletes
had the same amount of muscle glycogen.
And that it followed the same
pattern even in recovery.
So after the three hour run,
and then also two hours into recovery,
muscle glycogen was all the same.
– But the difference between them
was because the keto adapted athletes
were burning fat at twice the rate,
providing 80 to 90% of the fuel
during their endurance run at race pace.
So as Amy said, they ran them,
had them run on a treadmill three hours,
in the lab.
– In the lab, staring at a blank wall.
– The Keto adapted athletes mobilized
muscle glycogen at the same rate.
But they, it appears
that they recycled it.
They didn’t burn it all
the way to CO2 and water.
So it’s like, you know,
basically recycling that same carbon,
so they didn’t need to
eat a lot of carbohydrate
in their diet in order to regenerate
and maintain muscle glycogen stores.
But from a parental perspective,
how many ketogenic
enhanced diet performance,
one thing that the endurance athlete
tells is that when they’re keto adapted
they’re much less likely to hit the wall.
That is how the central nervous system
begins to shut down saying
you aren’t providing
me enough glucose to keep
my brain functioning.
So A, they can go for
longer periods of time.
And it appears to be
that because the brain
can function very well on ketones,
and is not glucose dependent.
And so for events lasting longer
than three or four hours,
when normally, again a
full iron man triathlon,
they have to eat continuously during
the running and the cycling
legs of those events.
One was that the athletes find
they need to eat far less calories
in the race in order
to sustain performance.
So that’s one aspect that’s beneficial.
And the other is what we
call power to weight ratio.
That many athletes find, no
matter how hard they train,
they can’t train themselves down
to an ideal, low level of body fat.
Say under 10%.
And for some athletes getting under 10%
is really important in terms
of the power to weight ratio.
And they find that when they
adapt a well formulated,
ketogenic diet they’re
better able to achieve
that optimum percent body fat
that optimizes the ratio of muscle
to muscle weight to body fat weight.
And again for those athletes,
oftentimes they will train on a high fat,
low carb diet to get ideal
body composition down.
And then they can add back what they call
strategic carbs, either
immediately before,
or during an event in order
to optimize glycogen as well.
And again this tends
to be athlete specific.
Each athlete needs to have some guidance,
but their own experience in figuring out
what works best for them
in terms of the degree
of carbohydrate restriction,
and the amount of carbs
that can be used strategically
to maintain optimum performance.
– Yeah, and I think we’ve talked
a lot about resistance training,
or endurance training, but I think
resistance comes up a lot too.
I think there was a study recently,
I hope I’m not miss remembering this.
I think it was out of
Donovan and Stephen’s group,
or he was involved in it somehow.
But they looked at 10
weeks of western diet
compared to a ketogenic diet,
and similar gains in terms of strength
and power during that time.
And also similar losses
of body fat and muscle
gain between the two groups.
So it doesn’t appear to
impair performance in any way.
– And not to get too
far ahead of the data,
Professor Volek at OSU is,
has completed the data collection
from a study they did with a high carb
versus a ketogenic diet in a group
of student athletes where they did
a intensive resistance training program.
And hopefully those data
will be reported this year.
But it will I think, emphasize the benefit
in terms of resistance training,
and maintaining lean body mass
and optimizing power to weight ratio.
– Sure, I think power to weight ratio
is really an important point.
Alright, our next question.
“Are there any benefits of fasting
“that you can’t get
through a well formulated
“ketogenic diet and
what do you think about
“autophagi and apoptosis?”
– These are hot buzzwords right now
in the research community.
There’s a lot of research been done
with basically animal models.
And what people talk about
autophagi and apoptosis
is basically changing either,
you know, regenerating cells, aging cells,
regenerating with–
– Yeah, it’s kinda–
– Replacement cells, and also–
– It’s kinda the cleaning system.
– A cleaning system, but also cleaning
up internal cellular machinery,
particularly involving
things called mitochondria.
And mitochondria are those
little furnaces inside cells
that actually do the
oxidative energy generation.
That’s where oxygen is consumed,
along with either fat or carbohydrate
to replace the high energy phosphate ATP,
and creating phosphate.
And so that machinery
constantly has to be repaired.
And there is evidence
that periods of fasting
can enhance that process.
– Several.
There’s been less research
with well formulated
ketogenic diets done long enough
to actually look at that.
And again the turn over of cells,
and the turnover of mitochondria,
that is how frequently it is replaced
is measured in weeks or months,
not in a day or two.
– Sure.
– And so particularly for human,
you know to have human specific results
it takes rigorously done studies.
And there aren’t that many groups
who have been able to
sustain ketogenic diets
long enough to really look at that.
And again, stay tuned,
because that’s an area
where Dr. Volek and his team
are on the forefront
of doing that research.
– Yeah, I think,
I’m certainly not an expert in this area.
But I think, autophagi can be stimulated
by reduced insulin, increased
glucagon, inhibition of mTOR.
So I know a lot of the
research is in fasting.
And ketogenic diets tend to mimic
that from a metabolism
standpoint in a lot of ways.
So I would assume that you would
be able to get some similar benefits
out of doing it for a long time.
Alright, “Have you tested
apo E genetic expression
“in study subjects, and does it have any
“predictive value in identifying
“so called LDL hyper responders?”
so we did not include genetic testing
in this research study so unfortunately
we can’t draw any conclusions,
or make any statements about that.
My understanding of apo
E is that one variant
of that, apo E4 is very highly associated
with increased cardiovascular risk.
– And increased LDL.
– And increased LDL, yes.
So in this case,
in terms of identifying
the LDL hyper responders,
this is a very complicated question
’cause my first question is
what is an LDL hyper responder,
and also if it’s a genetic component,
if they have apo E4 they probably
had a high LDL to begin with
before changing their diet.
So perhaps, we don’t have any data
that would be able to
answer that question.
But I would think that I would see
high LDL in that person before
they would even begin dietary changes.
– So the simple answer
is, we haven’t tested it.
– Yeah.
– In terms of doing the genetic testing
on our Indiana University
Health research population.
But the other point is,
that increasingly the
cardiovascular risk area
is moving away from a focus just on LDL.
So we think of LDL as
one tree in the forest.
– Yeah.
– And then we will be putting up a blog
post in the next day or two,
basically summarizing what we
have in our research paper.
So making it a little more digestible
for the non science reader to point out
that when we look at a
bunch of other factors
like inflammation, like hypertension,
that when we look at
those other risk factors,
so many of them improve independent of LDL
that even we assume that even people
with the apo A4 genotype
would probably still
then get a net benefit
from the ketogenic diet,
even if their LDL doesn’t respond
as dramatically or in the same
way as the other groups do
in terms of particle size and number.
– Sure, I just spent some time
at the National Lipid
Association conference
and the opinion of a
lot of clinicians there
is that they like to use a non HDL.
So even with LDL being a target they have,
they tend to also have
a target of non HDL.
And National Lipid
Association promotes that,
so I think the idea of relying on more
than one marker is certainly catching
on in clinical practice.
So if you’re just joining
us, we just wanna welcome you
to the Virta Facebook live Q and A.
This is Dr. Stephen Phinney,
and I’m Dr. Amy McKenzie.
If you like this event, and you wanna know
about more in the future you can follow us
on Facebook by following Virta Health.
Our next question says, “Is it possible
“for a person to have a really high
“hemoglobin A1c and yet
have decent triglycerides,
“meaning 150s or lower?”
Suppose it’s possible.
– It’s on average the higher a person’s,
or the less controlled a
person’s Type II Diabetes is,
so the higher their
hemoglobin A1c would go
the more likely they are to have
what we call atherogenic dyslipidemia
which involves a low HDL
and a high triglyceride.
So on average high triglycerides
and high hemoglobin
A1c values go together.
But people vary wide, quite
a bit from one another.
And it’s very possible
that somebody could have
a triglyceride under 150
which is the upper limit
of what is considered normal.
We like ’em under 100.
– Yeah.
And still have a high hemoglobin A1c.
The other factor is triglycerides can
go down very quickly when
you cut down dietary carbs.
If their hemoglobin A1c
– Very quickly.
value takes three to
four months to change.
So one might see triglycerides plummet
in the first, say month
of a well formulated
ketogenic diet.
– Sure.
– And the hemoglobin A1c is gonna tag
along quite a bit behind.
So typically we wait anywhere from four
to six months after people make the change
to a low carbohydrate diet
before we do that testing
so that the hemoglobin A1c can,
which is a slow responder catches up
to some of the factors
which respond more promptly.
– Sure.
(chuckles)
So this comment is, “Hi, Amy.
“Congrats on the award.”
Thank you very much.
“Is there a rough estimate of when
“two year Virta results get released,
“and are coronary artery calcium scores
“being calculated as well?”
– Tell us about the award.
– Oh gosh.
I mentioned the National
Lipid Association.
And we had submitted an abstract there–
– With you as first author.
– Yes.
Definitely a team effort
from the whole group.
We submitted an abstract focusing on
the cardiovascular risk factors
and their response at one
year to our intervention.
And also we took, because
of this concern about LDL,
we also took a closer look at
the change in LDL over time.
So we compared early
to late change in LDL.
And what we saw is that people
who had an early rise in LDL,
either LDLc or LDL particle number,
in the first 10 weeks, later saw
a decrease in a similar amount.
And those who had an early
decrease had a later rise.
So there’s a lot of you know,
potential explanations for this.
One is probably, partial
to Dr. Phinney with,
in this case, so if somebody
has an early rise in LDLc,
and they’re losing
weight, a lot of weight,
a significant amount
of weight in that time,
there’s a chance that their
cholesterol will go up
during that weight loss, right?
– Correct.
– And then it will go back to normal
following weight stabilization.
– And that appears to be because,
when people carry a fair degree
of extra body fat it soaks up cholesterol.
When you lose the body fat
it has to be mobilized.
So there’s a transient mobilization phase.
So again, we don’t draw conclusions
even after three or four months
if people are losing weight,
from the actual, the
measured cholesterol levels.
We wait usually til the end of a year.
Most people have stabilized
their weight by that time.
And that gives us a more steady state
measure of the cholesterol distribution
within the circulating lipids.
But there was a young investigator award,
and of the abstracts submitted
to this national meeting
Amy was the recipient of that award.
Congratulations doctor.
– Thank you.
(chuckles)
Definitely had some good mentors
along the way to get there.
So thank you.
Yeah, so we presented this at the National
Lipid Association conference last weekend.
Feel free to write to us
and ask us more questions.
– And the other question is when are we
gonna release our two year data.
– So two year data.
We’re two years into the trial now,
can you believe it?
– We’re more two years in,
but we recruited people over
about an eight month period.
And the last people
recruited two years ago
have now completed their
two year time point.
So we’re collecting the data,
and we’re analyzing that.
We can’t tell people about it
until we have it accepted for publication.
– Yeah.
– And again this is sometimes
pretty controversial data,
and it takes awhile, but we hope
by later this year we’ll have that data
published in the peer reviewed literature
and be able to share
it with this audience.
– And then in terms of
coronary artery calcium scores,
we did not include that as
part of the research study.
Although I know that sometimes it’s used
in the course of clinical care.
But unfortunately not part
of the research study.
We did do carotid intima-media
thickness measurements.
– That’s an ultrasound
of the carotid artery
to look at the thickness of
the lining of the artery.
And at one year we did not
see any threatening changes
in the population on the ketogenic diet
in spite of the fact that they’re eating
a lot more fat than our
parallel control group.
So that’s reassuring that
it wasn’t getting worse.
And we’re hoping at two years
that we’ll may be able to see a difference
between the control population
and our intervention population.
– We’ll test it and find out.
– Um hm.
– Alright, our next question is,
“What definitive total cholesterol numbers
“that are healthy for men and women?”
Oh, “what definitive
total cholesterol numbers
“that are healthy for men and women?”
Sorry, I can’t read today.
“And can you more clearly elucidate LDLp,
“small LDLp, LDLc, HDLc, and
what one should look for?”
– First point is, these
are not standard tests
that are available to all of us.
– But the LDLp, yeah.
– So particle size and number
still remain research tests.
And if you can get them done,
then you would need to
talk to the physician
that you went through to
have them ordered to be done.
In terms of total cholesterol numbers,
again that’s turning out to
be one tree in the forest.
There are a couple trees in the forest.
And again, we have no reason to,
dispute the total
cholesterol and calculate
LDL values except the have to be viewed
in the context of a wider
range of risk factors.
But we can’t get into specific numbers
for individuals at this point.
– Yeah.
Alright, so if you’re just joining us
we just wanna welcome you
to the Virta Facebook Live Q and A.
You have Dr. Stephen Phinney
and I’m Dr. Amy McKenzie.
We’re hear to answer your questions
on diabetes, heart health,
and ketogenic interventions.
Our next question is,
“Has research been done
“to determine if there’s a point at which
“high amounts of sodium supplementation
“can be dangerous or unnecessary?”
So there’s a paper that looks
at sodium consumption
and mortality, right?
And this is–
– There’s been a lot of research on it.
– Well I’m thinking of one.
I think you know what I’m
talking about, Donald–
– Donald, and then (interrupted)
Journal of Medicine from 2014.
If you go on our blog we have a posting
on sodium intake and adrenal,
and the why adrenal fatigue
is not a real medical issue.
And this is discussed in that paper
as we’ve referenced there.
Sodium is obviously a
very controversial area.
And people have almost, let’s say,
let’s say very intense convictions,
including dispute among
measuring scientists.
So this is not a resolved area as yet.
But in the study published
in the New England Journal
by this group, it’s a
international research consortium
studying lifestyle factors,
and health outcomes in
a couple 100,000 people
in 17 different countries.
– sure
It’s a massive study called the PURE,
P, U, R, E, that’s the acronym, study.
And they, rather than asking people
how much salt did you eat yesterday,
they actually took a urine,
got a urine sample from people.
From over 100,000 people and
then looked at sodium excretion
at that time point and their subsequent,
assuming that the day before
they’d eaten their usual,
whatever their usual salt intake would be.
Inaccurate if you were
dealing with a few people.
But when you have 100,000 people
it gives you a good measure
of range of sodium intake.
And then they looked at health outcomes
for four years afterwards.
The total mortality and coronary disease,
that is heart attack risk for
people was a U shaped curve.
And the bottom of that curve,
where the risk was lowest,
was between four and five
grams of sodium, not salt.
Four and five grams of
sodium intake per diet.
When people went down to the value
of where the current US recommendations
are at 2.3 grams per day,
there was actually a
measurable increase in risk.
And under 2.3 grams,
again these are people
in multiple cultures,
in many different countries.
But consistently there’s a rise
when you restrict sodium severely.
And as one increases sodium intake
past six or seven grams a day,
then the risk also begins to go up.
Now there are some
regions and some cultures
where people eat a lot more sodium,
and there is evidence that
that can be dangerous,
for instance some fishing
villages in Japan,
where the sodium intake may be in the 10
to 15 gram per day range,
that can be associated
with increased risk of stroke
and even heart disease.
So again, this is not a blanket permission
to eat vast amounts of salt.
But keeping, particularly when somebody
is on a ketogenic diet which enhances
the kidney’s ability
to clear extra sodium,
it appears that the beneficial range
for people who don’t have
significant heart or kidney,
already have significant
heart or kidney disease,
the beneficial range is in the four
to five gram per day
of sodium intake range.
– Yeah, I think an
important takeaway from this
is that it’s always in context.
It’s always for an individual person.
You have to consider all the different
things that they have going on.
And we can’t give a blanket,
across the board kind of recommendation.
But,
– If somebody has fluid
retention, or hypertension–
– Right, have to be much more careful–
– Requiring diuretic therapy.
We get people onto the ketogenic diet
and get them keto adapted,
and typically we withdraw
the diuretic medication.
Then we then begin to gently add
back the sodium to optimize
their circulatory reserve,
their wellbeing, and their function.
So again this has to be individualized,
and there aren’t, as Dr. McKenzie says,
you can’t give blanket recommendations.
And we’re not doing so here.
– Alright, our next question is,
“Too many calories, and too much fat,
“what is your take on these issues,
“and the low carb, high fat way of life?
“Will hitting your fat
macros lead to weight gain?”
Hmm, well I’m gonna start with saying,
basically what we just said.
Is that it’s very individual,
and I would say, what’s your goal?
Is your goal to lose weight?
Is your goal to maintain weight?
Is your goal to build strength and muscle?
All of these different factors
are going to change
what your macros may be.
At Virta we handle this
a little bit differently.
And we really focus on, you know,
it’s, we’re trying to
treat Type II Diabetes.
We really focus on carbohydrates,
getting an adequate amount of protein,
and then in terms of the fat,
we don’t count calories,
and we don’t prescribe
a certain amount of fat.
We really teach you
about hunger and satiety.
And we encourage people
to eat fat to satiety.
– So we try to stay away from macros
because when somebody comes to us,
and they carry extra weight
and they wanna lose weight,
what’s coming in is different
than what the body’s burning.
That’s how people lose weight.
And so again, this is as Amy said,
we individualize carbohydrate intake
to a restricted level where they can
get into nutritional ketosis.
We guide them to eat
protein in moderation.
But enough to maintain
lean tissue and function,
but not to over eat protein.
And then, we counsel people to eat fat,
add fat to satiety.
What that means is to
trust your instincts.
– Yeah.
– And so often, people,
when they’re eating
a high carbohydrate diet,
they don’t get that sense of satiety.
And they’re surprised at hey,
I, there’s still food on
my plate and I’m satisfied.
And we coach people through that process.
And one’s natural instincts
after a significant weight loss
is that the body will basically give
a person signals, yeah,
eat a little more fat.
But A we don’t counsel people to eat
a specific amount of fat,
and we definitely don’t tell people
to eat more fat to make your ketones go up
because that doesn’t work.
Ketone production is a function
of how much carbohydrates you eat,
which is the biggest driver.
Keeping it low enough to maintain
the liver in a state
where it produces ketones.
Not overeating protein.
Which protein is not a
very potent suppressor.
But it’s a moderate suppressor
of ketone production.
And then the other factor that
brings ketones up moderately
is adding a moderate amount
of endurance type activity.
And if people haven’t
had the energy level,
and they don’t have the lower extremity
and back problems that prevent exercise,
then exercise can be a factor was well.
– Yeah, and that’s for
many of our patients.
It’s been a really successful component,
just getting moving in
terms of a walk after dinner
or something like that.
Been really helpful for a lot of people.
– But we don’t encourage to purposely add
a specific amount of fat to the diet.
Only to add fat to the
point where that meal,
that day they have
adequate sense of satiety,
that they’re not
constantly thinking about,
and obsessing over food.
– Yeah, I certainly hear people say,
well if I add more fat
will my ketones go up.
But as you mentioned it’s
not much of a main driver.
And then if you have that thinking,
then you’re potentially
getting more calories
than you really need and potentially
stalling weight loss if that’s your goal–
– Again the process of keto adaptation
gives the body permission to
burn fat at twice the rate,
and at least initially, it doesn’t care
whether it comes from
inside, or from the mind.
– Alright, now our next question,
“Is there a protocol for
using the ketogenic diet
“as an adjunctive therapy
in the treatment of cancer?’
Working on this.
– Again a hot topic.
– There’s a lot of
animal research going on.
There have been a fair
number of human case reports,
and small uncontrolled
studies have been done.
There is now a lot of interest in doing
controlled, larger cohort studies.
And again not stealing
Dr. Volek’s thunder,
but he has one underway
at Ohio State University.
But to my knowledge there are no published
protocols at this point for treating
specific forms of human malignancies
or cancer with a ketogenic diet.
And that you know,
hopefully that will be forthcoming,
and with high quality research
within the next few years.
– Yeah I think when we were
at the Global Symposium
for Ketogenic Therapies
they were discussing this,
and talking about using
ketogenic diets in treatment,
as an adjunctive therapy for glioblastoma.
But it was a few case
studies, or a case series.
But yeah.
– Again, it takes, as we’ve discovered,
and at Virta, it takes a lot of education
and support for people to know what to eat
and how to sustain a well
formulated ketogenic diet.
And there’s a potential
application for vertigo
going forwards in providing
our continuous remote care
to support these kinds of studies.
– Sure.
– But, again that’s something we look
forward to in the future.
– Alright, so if you’re just joining us,
we just wanna welcome you to the Virta
Facebook live Q and A.
We have Dr. Stephen Phinney here
with myself, Dr. Amy McKenzie.
And if you would like to tune in again,
and join our future events,
you can follow Virta on Facebook.
Our next question says,
“Many have great concern
“about eating protein and fat
if they have kidney disease,
“or if their doctor warns
them that a ketogenic diet
“may cause kidney problems,
can you address this?”
– Yes.
– Yes.
I would say the risk to kidney function
from dietary protein intake,
is based more on a
presumption than on data.
When protein is eaten in moderation
there is very little evidence in,
when people have normal, or even modestly
impaired kidney function that it will
negatively affect the kidney function.
In our one year data from the IUH study
that we published a couple months ago,
the commonly used measure
of kidney function
is something called serum creatinine.
And that’s a product that’s produced
metabolic in the body
and has to be cleared
by the kidneys as a waste.
And the level of
creatinine over the course
of a year in people with
preexisting Type II Diabetes,
so the kidney’s are already being
challenged by their diabetes.
The creatinine level went down slightly,
but statistically significantly,
in the context of a well
formulated ketogenic diet.
So we saw no evidence at one year
of any negative effects
of moderate protein
in the context of carbohydrate restriction
and circulating ketones.
And we will have, hopefully
data from two year,
that we’ll publish from two years as well.
So again it’s, this is
not a high protein diet.
That, really we have to emphasize that.
Protein is eaten in, as
when we say moderation
it’s in a range that if
you’re talking about macros
in terms of what the
body is burning in a day,
we’re providing 10 to 15%,
at most 20% of the daily
energy intake of protein.
Some people advocate
higher protein intakes
with carbohydrate restriction,
let’s say with the Paleo diet.
And that does not appear to be necessary.
We don’t know whether that’s safe or not.
But certainly at the levels
that we counsel people
to do this, we have every evidence
of improving kidney function,
and no evidence that there’s a negative
impact on renal health.
– Alright.
I’m pretty sure this is a
question for the physician.
“Could diazox–
– Diazoxide.
– “Be helpful to ketogenic dieters?”
I have no idea.
– It hasn’t been studied.
– Can you tell us what diazoxide is?
– It’s a therapy that’s
used in acute care medicine
for people with severe hypertension.
– Okay.
– It does have metabolic effects
that might be beneficial.
But it’s a prescription medication.
And I don’t know of any evidence
that it would be any better than
naturally occurring ketone production.
But again, it’s an area
where I don’t wanna speak
from presumption, and I don’t know
published evidence that
would support its use.
– Okay.
“Do we need to supplement iodine
“since we are using sea salt?
“If so, how much?”
– So most commercial salt is
supplemented with iodine–
– Iodized salt.
– Because if people
don’t get enough iodine
they can have impaired
production of thyroid hormone
because it has, each molecule
that the thyroid makes
has to have four iodines on it.
In the past, in areas where people
aren’t close to the ocean where sea food
contains a fair amount of
iodine, even if sea salt doesn’t.
Iodine depletion can lead
to what’s called goiter.
The thyroid gland hypertrophies
because it wants to make more.
But it doesn’t have
enough of that mineral.
– Sure.
– If somebody eats,
takes a standard, basic
multivitamin,
– Multivitamin.
That contains plenty of iodine.
Much of the salt is
used in food preparation
is iodine supplemented,
so again prepared foods
will have it, and even if one chooses
to eat a version of sea salt
that’s not been iodine supplemented.
So we don’t have any evidence that folks
eating a well formulated ketogenic diet
and using sea salt rather than
commercial supplemented salt
will see an iodine deficiency.
Theoretically possible.
We do counsel people that
a seven cents per day,
standard, low iron multivitamin
is a very, very inexpensive
insurance policy
that will do no harm and cover
some of these basic issues
were they ever to become a factor.
– Sure.
Our next question is,
“What is the maximum limit
“grams of carbs for weight maintenance?”
This is a very challenging question.
“What is the maximum limit of grams
“of carbs for weight maintenance?”
It’s a very challenging question
to give an answer to broadly.
I think it depends on the person.
– Sure.
As Jeff and I, I think,
if that coined a term,
certainly promoted the concept
of diabetes as a form of
carbohydrate intolerance.
And diabetes is a disorder of,
Type II Diabetes is a disorder
of predominately insulin resistance.
When people reverse that
with a well formulated
ketogenic diet they can increase
their carbohydrate tolerance.
At the other end of the spectrum,
there are people, and we know people
who eat a lot of carbohydrates
on a low fat diet,
and remain very thin, and very healthy.
They have a very high
carbohydrate tolerance.
So we range, as humans from
very carbohydrate intolerant,
that’s Type II Diabetes,
to those skinny high carb people
who seem impervious to even a
high intake of refined carbs.
They’re highly carb tolerant.
So humans vary in a range.
And then we vary with age.
And I would say 30 years ago I was
much more carb tolerant than I am now.
And so you know, for me, 50 grams a day
of carbs is about all my metabolism
will handle without having health effects.
But other people can
handle 100 to 150, 200,
so again, it has to be
highly individualized.
And so we don’t have rigid prescriptions.
And at this point people
really have to find
through coaching and a bit of trial
and error what works for them.
And that’s what makes the
Virta treatment complex,
and why it makes it difficult
to put it into a standard
cookie cutter approach.
– Yeah, definitely
individual to each person
what their goals are, what
their insulin resistance is.
Definitely have to work with
each person individually.
Our next question says,
“Are there discreet groups of people
“who tend to be at greater
or lesser risk of losing
“muscle mass if protein intake is too low?
“How about groups of Type II Diabetics
“who react differently to
different levels of protein?”
Hmm.
– We do know that people
vary in their protein needs.
There have been very rigorous studies done
in the context in a quote, balanced diet.
And actually when I was a
graduate student at MIT,
oh, many decades ago,
some of my teachers there were doing
studies to measure
precisely how much protein
the average, normal person needed.
– Um hmm.
– I don’t wanna cast any spurgeons,
at students at my alma mater.
But they were using MIT undergraduates
as their normal subjects,
and some people from Harvard might say
that those weren’t really normal people.
Just a little bit of Cambridge
politics there, sorry.
But what they found is that keeping
the protein intake very low,
down to the point where the people
were just hanging on to their existing
lean body mass, was a specific number.
But some people were
doing just fine at that.
And other were losing these tissues.
So the group average doesn’t represent
what the individual needs.
So there is quite a bit of human diversity
in terms of their protein needs.
We also know that that protein
need goes up with aging.
That older people tend to be less able
to maintain lean body mass
when protein is restricted.
And then illness, particularly
inflammatory illnesses
can increase protein requirements.
And certain medications will
increase protein requirements.
So again, there’s a lot of variability.
The number we’ve chosen to focus on,
which centers around an intake
of what we call 1.5 grams of protein
per kilogram of reference weight,
which is, it basically
makes some assumptions
about how much lean
body mass a person has.
We pick that number because
for the vast majority
of people that we’ve
tested that turns out to be
a adequate amount of
protein, with some buffer.
But not so much that it
suppresses ketone production.
And so again, but we, our coaches
will work with people
if they’re struggling
to get their ketones up in a good range.
They can dial back a bit
from that level of protein.
Other people, if they’re
doing resistance exercise
and wanna build lean body
mass they can add a bit more,
as long as it doesn’t
compromise ketone levels.
So again, it’s individualized
through our biometric
monitoring and our coaching.
– Yeah, one thing that I
was really surprised about
when I was working clinically was,
patients who gained lean body mass
once they started doing a ketogenic diet.
Can you talk about that a little bit?
– Well we’ve seen that in
metabolic work studies.
That some people come in,
perhaps because they have
been doing restrictive dieting
for an extended period of time.
And again, when you restrict calories,
the body becomes less efficient
in the use of protein.
So people that are constantly restricting,
trying to lose body fat may end up also
compromising lean tissue.
– Compromising protein.
When we get them on a well
formulated ketogenic diet
the fascinating thing is satiety goes up.
They no longer feel like
they’re restricting.
But they’re eating fewer calories.
And yet they gain lean body mass.
And that implies that
there is something about
the nutritional ketosis that enhances
the body’s ability to build
and recover lean tissue.
And we hear that from athletes as well.
Particularly on the recovery point.
Again areas that we see evidences there,
but we really haven’t had the resources
to study it rigorously.
– Our next, who.
Oh, sorry.
We have time for two or
three more questions.
So please ask yours in the
comment section under the video.
“What is the best time to test
“for blood ketones to verify ketosis?”
we’ve gotten quite a lot of these,
it depends questions today.
Sorry, this is another one of
those it depends questions.
So I apologize.
It really varies between people.
In general I would say most people
have lower ketones in the morning,
and higher ketones in the
early afternoon, evening,
generally kind of in the before
dinner, dinner time range.
But I’ve definitely seen
exceptions to that rule too.
So I think this is something that
it’s good to test a a
lot of different times
and see where you are at
different points in the day.
It’s also good to test at different time
to understand how your
body reacts to food,
how your body reacts to exercise,
and you can really understand
how you work with this.
But then ultimately it’s up to you,
and it’s up to you and
how your pattern works,
and really what you’re looking for.
– In the past we thought that ketones
primarily were just a good replacement
for glucose to feed the brain.
Which means you had to have
them there all the time,
’cause your brain is
burning energy continuously,
minute by minute, and so we thought
ketone levels should be up
in a good range all the time.
And now it turns out that ketones,
particularly beta Hydroxybutyrate
has almost a hormone like action
signaling various cells
in the body to do things,
and some of those come through changing
gene activity as an apo genetic effect.
And that maybe something,
that if one gets up into it,
an effective apo genetic signaling range
at some point during the day,
the benefits will carry on.
And so there’s more to be explored here.
But as Dr. McKenzie implied
– I can’t wait for that.
People vary at different
time points in a day.
And you know, if you wanna
get positive feedback,
and see a good quote, you know,
a higher level
– a higher level.
Test yourself typically in the afternoon
after it’s a half hour, from anything
from a vigorous walk to working out
in the gym it will probably go up.
– But if you wanna know your lowest
you test at your lowest time point.
So it depends on what,
it really depends on you and
what feedback you want to get.
So our next question is, “Have there been
“any updates to the
literature around taking
“exogenous ketones for general health,
“energy, and neurological disorders
“since your March blog post?”
I don’t know if I’ve
seen anything recently–
– There really hasn’t, I haven’t seen
anything that enhances
what we already know.
Again there are, this a
very active area of research
with ketone supplementation.
And research being done at Oxford.
– Yeah.
– Dr. D’Agostino’s group at
University of South Florida
and Jeff Volek at Ohio State University
all have active protocols under way.
And as the range of ketone supplements
that can be consumed,
the range of formulations
is increasingly available,
and particularly
as the cost comes down we’ll–
– Yeah that too.
– Hopefully have an understanding
of how best to marry the
exogenous ketone usage
with also enhanced endogenous production
by appropriately
restricting dietary carbs.
– Our next question
is, “How do you address
“those doctors who advocated whole foods,
“plant based diet to
restore insulin sensitivity
“and thus control Type II Diabetes,
“and also decrease insulin
needs for Type I Diabetics?
“It seems their way of eating
“is the complete opposite
of a ketogenic diet.”
– The answer is, not necessarily.
One can do a, definitely a low carb,
and even a ketogenic diet
as a vegan vegetarian.
It’s easier to do as
a lacto ovo vegetarian
where the majority of one’s food is coming
from non meat sources, and particularly
from plant sources.
And I actually was, I participated
in a symposium recently in Chicago
where there was a
advocate of total fasting
for a duration of like
two or to three weeks,
followed by a plant based diet.
And he presented evidence of reversing
Type II Diabetes with that approach.
The total fasting was done
in an inpatient setting.
This is obviously, would
be a very expensive
way of using this kind of therapy.
And his data was impressive in terms
of the people he selected to present.
But these are people who
chose to A, pay the money,
and B, go through the fasting.
And at the end we agreed very collegial
that there are some people who are
well suited to do it that way.
And there are many people,
and certainly we found quite a few of them
in the Lafayette, Indiana area
who were able to do it
with the Virta program.
The two are not mutually exclusive.
And so in the future as,
particularly as there are rigorous studies
done with the plant based diet,
because up til now it’s
been more anecdotal
and ideological than science based.
But as people demonstrate
what percent of people
who are recruited into
such an intervention
can succeed at that, not just
for months, but for years,
we’ll be able to offer people,
basically a menu of
options rather than saying
this is the way to do it.
And I don’t think there’s one carbon,
or one cookie cutter approach
that fits every human
being’s metabolic needs.
– Yeah, and I also think
there’s preference,
and lifestyle choice
too, is that you have to,
we were talking about doing
something sustainable.
You have to choose something
that’s going to work for you
both in terms of health
and your metabolic needs,
and your lifestyle, so
you have to kind of find
the balance between the two.
And for some people it
might be one direction,
and for some people it might
be a different direction.
Definitely have to consider what
the patient’s goals and values are.
– Agree.
– Next question says, “How will I know
“if I am no longer insulin resistant?”
That is a challenging question to answer.
We could tell you about
your glycemic control.
You know there’s certainly a range
of understanding your blood glucose,
and how much your blood glucose varies
in terms of you know, what is your average
blood glucose over a period of time
when measured by A1c.
In terms of insulin resistance,
I guess the gold standard
would be the clamp?
The glycemic clamp?
– There’s actually a sign,
a research test where you
infuse insulin in one arm
and you infuse glucose in the other arm
and you see how much glucose it takes
to overcome the effects of insulin.
– Sure.
– The more standard approach is to do
either a fasting insulin,
and a fasting glucose
in the morning and that
is a calculation called–
– A homeo–
– Homeostatic measure
of insulin resistance.
And that’s something that
can be done by any physician.
It’s a standard test
with just one blood test.
If you wanna be more
rigorous you could do a,
and we don’t advocate this,
have people drink either a
50 or 75 grams of glucose
and measure the body’s insulin
and glucose response
over either two hours,
up to five hours.
But the home IR is a pretty good test–
– Yeah, it’s been validated against–
– It’s been validated in our,
what was the reduction
in home IR at one year?
Was it like 60%?
– I don’t remember off the top of my head.
It was significantly reduced.
Unfortunately I don’t remember the number.
– It was a very large reduction.
– Yeah.
– And so those are the ways,
but if you were taking diabetes medication
for Type II diabetes, and
you’re off those medications,
and your blood glucose control is better,
and your hemoglobin A1c
is down significantly
you’re markedly, you’ve markedly
improved your insulin resistance.
That you can know for sure.
– Definitely.
So thank you so much for joining us today.
If you’d like to have more information
on ketogenic interventions
and their effect
on diabetes and heart health,
follow Virta Health on Facebook,
and check out our research
on virtahealth.comresearch.
– Thank you.