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

– 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 virtahealthcom/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 23 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 15 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 virtahealthcomresearch – Thank you

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