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

October 9, 2019 0 By Bertrand Dibbert

– 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.