The Peter Attia Drive - #116 - AMA with Dom D’Agostino, Ph.D., Part I of II: Ketogenic diet, exogenous ketones, and exercise

Episode Date: June 22, 2020

Back by very popular demand for a special AMA episode, ketosis expert Dom D’Agostino joins Bob Kaplan, Peter’s Head of Research, to address many lingering questions about the ketogenic diet, exogenous ketones, and exercise for overall health. Dom also shares valuable insights from his personal experience with training, supplements, intermittent fasting, and other nutritional strategies to optimize his own health and performance. If you’re not a subscriber and listening on a podcast player, you’ll only be able to hear a preview of the AMA.  If you’re a subscriber, you can now listen to this full episode on your private RSS feed or on the website show notes page. We discuss: Dom’s recent and ongoing projects [3:00]; Benefits of a ketogenic diet for an otherwise healthy person [7:00]; Book recommendations to become more knowledgeable about a ketogenic diet [11:30]; Best devices for measuring ketones [13:45]; Genetic factors that influence how someone responds to the ketogenic diet [24:45]; Ketogenic diet for those with the APOE e4 allele [28:15]; Impact of long-term ketogenic diets on thyroid function [34:25]; Low-carb and ketogenic diets for appetite control and weight management [39:00]; Ketogenic diet and the microbiome [43:00]; Comparing monounsaturated fat versus saturated fat on the ketogenic diet [45:55]; Implications of long-term genetic and epigenetic adaptations to a ketogenic diet [47:45]; Why some people see a rise in LDL-C and LDL-P when on a ketogenic diet and what they can do about it [50:15]; Should someone with familial hypercholesterolemia consider a ketogenic diet? [55:00]; Exogenous ketones—benefits, therapeutic uses, and ketone supplements that Dom has tested [56:45]; Ketogenic protocols for management of traumatic brain injuries [1:06:00]; Comparing the benefits and therapeutic uses of various medium-chain fatty acids—caprylic acid (C8), capric acid (C10), MCT oil, and coconut oil [1:08:45]; Nootropics, caffeine, and other stimulants [1:16:15]; Supplemental use of testosterone, DHEA, and creatine for muscle growth and performance [1:23:45]; Impact of fasted-state training on strength and performance [1:30:15]; Stacking exogenous ketones with MCTs for optimal effectiveness [1:33:30]; BCAA supplements during a fast for muscle preservation [1:35:45]; What app is Dom using to track his macros? [1:42:00]; Getting enough micronutrients while on a ketogenic diet [1:47:15]; Ideal macros and getting enough protein for strength training in ketosis [1:48:15]; Pros, cons, and ideal macros of one meal a day [1:51:15]; Dom’s take on “carb backloading” [1:54:45]; Dom’s take on “carb up” days for ketogenic dieters [2:01:00]; Dom’s thoughts on the carnivore diet and the paleolithic ketogenic diet [2:05:30]; Advantages of the ketogenic diet for extreme endurance athletes [2:10:30]; Impact on strength, power, and performance during the adaptation period of the ketogenic diet [2:14:00]; Fasted-state elevation in growth hormone and its impact on training [2:17:45]; Is it possible to build muscle on a ketogenic diet? [2:23:30]; Why Dom took a year off from weight training [2:28:00]; What does Dom do for cardio exercise? [2:30:45]; Protocols for hard training recovery [2:33:15]; Dom’s personal approach to fasting, time-restricted eating, and sleep [2:35:45]; People, books, and other resources that shaped Dom’s training and nutrition [2:38:45]; and More. Learn more: https://peterattiamd.com/ Show notes page for this episode: https://peterattiamd.com/domdagostinoama01 Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on Facebook | Twitter | Instagram.

Hey everyone, welcome to a sneak peek, ask me anything, or AMA episode of the Drive Podcast. I'm your host, Peter Atia. At the end of this short episode, I'll explain how you can access the AMA episodes in full, along with a ton of other membership benefits we've created. Or you can learn more now by going to PeterittiaMD.com forward slash subscribe. So without further delay, here's today's sneak peek of the Ask Me Anything episode. Hey everyone, welcome to a special Ask Me Anything episode. And when I say special, I am not kidding. You'll see why in a moment. This is gonna be part of a two part series

with Dom Dagustino. Now some of you may know Dom's name as he was, oh, I don't know, probably our fifth guest when this podcast kicked off in 2018. Dom's episode to this day remains one of our most popular episodes. And it's for that reason that we decided to go back and Bring him back on in the format of a Q&A

We had this interview scheduled for a long time and right when it was scheduled to happen something came up something very important Came up where I had to go away and I had to go away such that I couldn't actually do the interview We all pow out and contemplated, should we reschedule it for a little while, Dom had already set aside the time to do it. And in the end, the consensus view was, why not have Bob Kaplan, who many of you know from this podcast, why not have Bob do it, Bob and Dom already have a great rapport. There's probably nothing here that Bob would do that I wouldn't do in vice versa. So Bob and Tom ended have a great rapport. There's probably nothing here that Bob would do that I wouldn't do in vice versa. So Bob and Tom ended up doing just that and they ended up sitting down

for a heck of a lot longer than anticipated. Both true to the sport, Bob wanted to go down every avenue and Dom left no stone unturned. And that's why it's being divided into two parts so that a normal human being could actually listen to it in a reasonable sitting. Now, in the first episode, Bob and Tom cover a lot of questions, both general and specific about ketogenic diets and ketosis. They also do a bit of a deep dive on the impact of ketosis on different forms of exercise. Now, as a reminder, Dom is an associate professor at the University of South Florida, where he teaches at the College of Medicine and the Department of Molecular Pharmacology and Physiology. He focuses on neuropharmacology, medical, biochemistry, physiology, neuroscience, neuropharmacology.

As a reminder, I believe Dom actually got his PhD in neurobiology. For those of you who haven't listened to it, it might even be worth going back and listening to at least part of the first discussion I had with Dom in 2018, because it gives you an idea of how a neuroscientist became one of the most credible voices on ketosis, ketogenic diets, and all things ketone-related.

Lastly, it is important to note that while Dom is answering specific questions and scenarios he is not giving medical advice, everything in this podcast is for general, informational purposes only, and does not constitute the practice of medicine, including the giving of medical advice. So without further delay, please enjoy part one of the AMA with Dom Dagestino. Alright, welcome to a very special AMA with Dom D'Agostino. Dom, how you doing? I'm doing well. Thanks for having me.

Absolutely. So it's been almost two years since you were on the podcast with Peter. I met you in New York at that time. I think it was the summer of 2018. I know how time flies. I was just talking to my wife about that. She would ask me what I'm doing this week, and I said, I got the podcast with Peter,

and she's like, didn't you just do what? And I mean, she was happy that it was on, but we were just amazed at how fast that time flew by. Yeah, the time in New York. So I give you credit for dealing with New York. It's always an adventure every time we get. Absolutely. So since then, we certainly received a bundle of questions and then Peter went

on social media and asked if there were any questions for you and particularly what you've been up to in the last couple of years. But maybe you could fill us in just in general a little bit about ketosis or how do you get into ketosis and what you've been up to in the last couple of years? Sure. Well, I guess, yeah, like I said, the last two years. And we are really trying to move the laboratory science into human applications. So we've been doing quite a bit on that front. And that has been pretty time consuming in regards to kind of setting up all the IRB protocols.

We're doing quite a bit with NASA extreme environment mission operations research where I was a crew member for mission 22 and my wife was a crew member for Nemo, the acronym they used for that for Nemo 23. And that involves looking at everything from cognitive function, body composition, gut microbiome, sleep, heart rate variability, stress. So we have like an IRB protocol for each one of these and we're evaluating the effects of hyperbaric environments, extreme environments on human physiology and all the things that I mentioned.

And I just happen to be on a ketogenic diet for my thing, but we're trying to kill like baseline data for future missions underwater where we can have an intervention, a dietary intervention, for example, ketosis. So that has been a big focus of our research. Another space analog mission would be high seas. So we're preparing for that. Of course, all this stuff is being on hold now because of COVID-19. So that's kind of outside the lab. Inside the lab, we focused a lot my student now, Dr. Andrew Kutnik, last week actually, he graduated.

And his research, PhD research was focusing on cancer, kiseya. And we just got his manuscript, a massive manuscript published in IMPACT Journal. And really happy with that. And we just got his manuscript, a massive manuscript published in IMPACT Journal. And really happy with that. And we have some interesting findings evolving out of that research, looking at the effects of ketones on mitigating cancer cacaxia and wasting associated with metastatic cancer, in the model that actually Thomas Seaford developed. And we're looking at Kabuki syndrome. We're looking at various genetic diseases and developing ketone metabolic therapies as a means to treat these

diseases not only from a metabolic perspective, but as a means to influence epigenetic pathways that may be used to treat the disease. And the model that we're using, for example, for Kabuki syndrome was developed at Johns Hopkins. So we were able to work with the folks there and get access to this animal model, which we're breeding up. And like, things are on hold now, but we're doing pretty well. On these experiments, getting them started up, and that's becoming another PhD dissertation for first year student of Vine, Sarah Moss. And then we have a lot of little pet projects on the side. I could talk about forever, but I think there's kind of the main ones we're working on.

Cool. We're going to double click on hyperbaric oxygen, cancer cakexia, and things like that. I know that there are some questions that came in on that. But first, there were a few general questions for you. The first being, is there a case for one to two months of ketosis a year if I am perfectly healthy and don't have any problems with carbs? I don't like to use this term, but you have to sometimes. It depends on the individual and what their goals are. But I do think there's definitely benefits that you can derive out of, I guess, what you'd call intermittent ketosis. The main thing is I think one of the main benefits is that it promotes metabolic activity. And so having your body, we're relative. Most people are adapted to frequent carbohydrate feedings, so their metabolism

is not adapted to using fat as a major energy source during times of limited carbohydrate availability or calorie availability. So during periods of fasting, by promoting metabolic flexibility, and I believe when you go into a state of ketosis, whether you do it with ketogenic diet or fasting, it changes. It actually activates a genetic program that actually can allow you to burn fat and make ketones more efficiently. And I think once if you do that a couple of times, we have muscle memory, work out, you take time off, it takes a little bit of time to get back to where you left off, but you get back to that level very, very quickly.

And the same thing happens with your metabolism. I would say there's a metabolic memory associated with it. So the more you do it, the more benefits you derive from it over time. I think there's personal development reasons for intermittent ketosis. There's logistical reasons, too. You could be a difficult period of your life that you don't have a lot of time, just based on work or other priorities and eating ketogenic actually saves time. I know Peter was doing something like a three-day fast every month. I think that people could implement this idea. I think the same thing could be achieved instead of fasting.

You could do six days, if you've a restricted ketogenic diet, every month. And I think you get the same benefits if you didn't want to just do fasting, if people have an aversion to fasting three days out of the month. The thing to target would be the glucose ketone index. And if you're doing, for example, intermittent ketosis, this guy has a question, and you want to derive benefits of it similar to fasting, you could restrict calories

like 50% on a ketogenic diet and do that for six days a month. And I believe you would achieve, at least for me, a glucose ketone index between 1 to 2. And if you do your blood work, you'll find that you'll have almost a similar level of insulin suppression, especially if you measure that insulin even during that week of feeding just prior to eating a meal. If you do, restrict a ketogenic diet and combine that with time-restricted feeding. You're hitting all the major drivers of the benefits that you'd get from fasting,

like suppressed mTOR, suppressed insulin, your body sensing low ATP, it's probably stimulating autophagy, although we don't have a good means to measure that. So that would be my suggestion if you want to, you don't have any problem with carbs, but you want to get some of the benefits of ketosis to maybe try once a month to do five or six days or five to seven days, let's say, of a restricted ketogenic diet, which I think is pretty easy

to do. That makes sense. One thing that Peter was doing, previously he was doing one week fast and he would sandwich it between two weeks, a week prior, he would go on a ketogenic diet and then a week after he would go on a ketogenic diet. And one thing that I noticed too, just with my own playing around and probably other people have experienced this, is that if you're trying to dial in that glucose ketone index and I think, is it like, directionally, you want

it basically one to one with glucose and ketones? If you can achieve that, that's pretty good. I'm a little bit more loose on it. I think if you can achieve one to two, just based on my observations from fasting to ketogenic diet, I think you start to derive a lot of benefits. And I quantify that through the level of insulin suppression. I've been able to kind of record from that. So I've been measuring, taking a lot of insulin measurements. Yeah, that makes sense. So the second question, what are some books you'd recommend to get knowledgeable on modified keto? And I guess the preface there is that you do a form of a modified ketogenic diet, at least last time I spoke to you, you were doing that.

Yeah, that diet has been kind of evolved over the years, but some of the books that really influence me that are kind of mandatory reading for people entering the lab are Jeff Bullock and Stephen Finney guess since we've last spoke, a couple really good books have come out. The key to Genic Bible is a fantastic comprehensive overview of the key to Genic diet and it's got everything from recipes, it breaks down the terminology, it's written for the lay person and the people really interested in the science to. Keto answers is a great book for the layman and it really breaks down what a modified ketogenic diet is, recipes, suggestions on a lot of tips, troubleshooting and things like that. Now if you really want to geek out on the science, I would definitely recommend, I know a lot of listeners are interested in the science,

the ketogenic diet and metabolic therapies. So Google, that term, ketogenic diet and metabolic therapies, primary author would be Susan Masino. I am the editor of that, so kind of disclose that I do get royalties. It's from Oxford University Press, and it's a book that really delves into, very deeply into the science. And I guess the book that had probably one of the biggest impact on me for the modified ketogenic diet or the modified acnes, which sort of evolved around 2008 when I became aware of it, was the more of a clinical book by Dr. Eric Kossoff from Johns Hopkins.

So if you're interested in a modified ketogenic approach from a clinical perspective, just look up Eric Kosoff from Johns Hopkins and check out his book on the modified ketogenic diet. Okay. So they're all the books right now sitting next to me on my shelf. So once I'd recommend. Yeah, I'd recommend those as well. Particularly the art and science of low-carb performances. Not a pamphlet, but it's not a novel either. Now, it's a quick read. Yeah. Yeah.

Update on ketone measurement devices, breath, blood, etc. I guess I would say urine. I'm not sure if there are any other ways to measure. But then about covers it. Yeah, the urine strips are actually something I don't discourage against and I think they could be a Good kind of yes or no if you're in ketosis and it you know it gives you a relative reading but I Ten not the the Siemens multi-stick SG is pretty good and it gives you other parameters on the urine strip But when it comes to blood meters which I I've used most often, the precision extra

remains one of the meters I use almost on a daily basis. Abbott Lab makes that. It's well validated, it's very reliable. It's got a track record people publish with it. The newer device that's out is the keto mojo. And I have the keto mojo GKI, which has the glucose ketone index sort of incorporated into the algorithm here.

And what I find is that the keto mojo device, it's got a lot of pros, a lot of benefits to it. The strips are much cheaper. It does the GKI, of course. It's a little bit larger, so it doesn't, it's a little bit bigger than the precision extra. It records higher beta hydroxybutyrate in the low ranges. So if I'm 0.5 on the precision extra,

I'm usually like 0.9 or like a 1.1 with the keto mojo. Now, when my ketones get into like the two and three range, then they're pretty decorally. I think the keto mojo may be measuring slightly higher in the low ranges, but I also think that the previous decision extra may be measuring slightly lower. And the rents, for example, if I was point eight from an assay we do in the lab, I think the keto mojo would maybe have me at 1.0, whereas the precision extra would be 0.5. So I think there's somewhere in the middle is the correct one, but they're relatively they're easy to use and I think they're devices that I use pretty much on a daily basis.

The breath acetone meter, now that's what I've been spending a lot of time evaluating that technology. Biosense makes this device and in regards to breath acetone meters, I would say it's like a next level kind of stuff. The breath acetone does correlate well with beta hydroxybutyrate from my measurements if you're in a fasted state. So it's exceptionally good in a fasted state. There are some drawbacks to it, I think. For example, if I have wine or if you eat a meal, you're going to get a false positive, which means you're going to get an elevation breath ketones that's outside of the spectrum where you're really at. And that suggests that it's picking up something other than breath acetone. Definitely picks up breath alcohol. But it is pretty reliable. I've used it hundreds of times and that would have been thousands of dollars worth of strips and it correlates well,

especially if you're into fasting. And if you're following a ketogenic diet and you just abstain from food or chewing gum or alcohol or whatever for a good hour, then the measurements are pretty correlate pretty well with beta-idroxamputary in the blood. A couple of years ago, I had a, what was it called, ketonics, which I think was measuring acetone. And it wasn't, which I say, quantitative. It basically gave you a, I think it was a green, a yellow, or a red. And I think green meant that you probably not in ketosis. And then yellow was moderate. And then red was something along the lines of deep ketosis. I don't know if this correlates with maybe the urine strips or something like that.

Is the one that you have? Is there something that you can quantify in terms of the amount of acetone? Yes, they have ACEsEs and 10 ACEs. You might see some of the measurements I've been posting like on Instagram. 10 ACEs would correlate to 1.0 beta hydroxybutyrate pretty much. So it's like an order of magnitude above. And I think I got that right, but you might want to check out the specs on the website. So, yeah, it's just in order of magnitude higher, the numbers. And these numbers were developed to

sort of correlate to beta hydroxybutyrate. I think that's how it's more or less calibrated, sort of in that way, the algorithm. and they've done quite a bit of work at bioscience to make the meter reliable, which I'd, on my third one now, I have to say, because at the first two, I think we're sort of beta versions, just sent the other one back and I have a new one now, but I carry it with me in my pocket. It's been to many countries.

It worked well and it's reliable. So the ketonics meter, I has gradually become more quantitative, so you might want to check to see the latest version of that. Although I have to say that the biosense breath acetone meter is the most quantitative breath meter that I've seen so far and they've done quite a bit of research. One other drawback is that it takes about a minute or two to calibrate. So you have to press it and kind of wait to blow in it. If you're kind of impatient,

you could probably take a blood measurement a little bit quicker. And if it's windy out or you're outside, things sometimes it get an error reading. But generally, I'm testing it my desk, I'm testing inside. And I do like measuring blood, but this is a very close second to my favorite measuring device. I'm gonna quantify ketosis.

Breath acetone is a very strong indicator of fat oxidation. So if you're just using it as your following ketogenic diet, burning fat, that acetone is basically derived from fat. So you have, it's a very good quantitative measurement of fat oxidation. Also, from the clinical perspective, which I'm most excited about, is that a lot of kids do not like to get their finger

pericked, obviously. A device like this is very appealing to children who have epilepsy, and breath acetone correlates really well with seizure control. So I'm excited that this technology can make it into the clinical realm, especially in epilepsy. Yeah, I was going to ask you actually between beta hydroxybutyrate, acetoacetate, and acetone, if it's actually telling you something a little bit different physiologically or biochemically that

maybe one might tell you a little bit more about the availability versus utilization and it sounds like with the acetone it might actually tell you a little bit more about the ketones that you're actually burning. And I think you mentioned this that instead of a glucose tolerance test, you thought of like a ketone tolerance test, when you think about it, if you're utilizing the ketones quite efficiently, then this is one of those things that I think some people get into ketosis, meaning they get into the diet or ketogenic diets, and it's almost like a challenge to see how high you can get your BHB, like how higher your ketones, but in some ways you think, well, maybe I want to utilize those things, and if I'm utilizing them, then maybe it will be the substrate might be

smaller for BHB, but it, it sounds like that's right, that the acetone tells you a little bit more about the utilization of ketones versus maybe BHB. Yeah, you bring up a good point. I think if beta hydroxybutyrate stays circulating in the blood longer, it's more likely to, you're gonna have more acetone as well. And that can spontaneously decarboxylate or acetal acetate, I should say.

And you maintain a ratio of about four to one. And some measurements I've seen people at six to one beta hydroxybutyrate to acetyl acetate. So if your acetyl acetate is elevated in the blood, that spontaneously decarboxylates to acetone. And that's what it's very volatile. So you're breathing that off. But in regards to the ketone tolerance test,

yet, if you're using ketones at a fast rate, they'll be less beta hydroxybutyrate in acetoacetate available for spontaneous decarboxylation. So that's that volatile organic compounds not going to show up in the breath. So if you exercise, acetone goes down. I did yesterday and noticed that a workout can really lower my acetone level, breath ketone, as it does with blood, beta-hydroxybutyrate.

But if I'm working my metabolism up and I come back to my desk and I'm sitting there and you have that post-exercise elevation and metabolism, then you start seeing that acetone starting to shoot back up again when you're at rest because the ketones are, you've ramped up metabolism, fat oxidation, ketogenesis, and you start building up ketones, but you've ramped up metabolism, fat oxidation, ketogenesis, and you start building up ketones, but you're not using them. And athletes do really well, I guess you could say, on a ketone tolerance test,

because if you give them a bolus of exogenous ketones, they clear it from the system pretty quick. And they clear it very quick when they start exercising. So which is a really good indication that they're using that metabolic substrate for fuel. You talked about this a lot. George K. Hill, his study, the 40 days of fasting, and he looked at what he looked at. He looked at beta hydroxybutyrate. And I think he on the same graph he had a Ceto acetate and free fatty acids. I don't think that he had acetone, but maybe a future

question, I don't know if it's in here, but something about free fatty acids and acetoacetate seem pretty close, that they were pretty close together as far as substrates, but gets into the idea of how many free fatty acids are we burning compared to maybe ketones as well in the interplay between those two? Yeah, there's some interesting dynamics going on for sure, and I think you'll notice a couple things from that work. You'll notice that what they didn't measure acetone because it's very hard to measure. We've just doing the experimental procedure to store the blood to make an acetone measurement possible through gas chromatography and aspect. It's quite an achievement. So it's kind of hard to do because it's volatile.

But you'll see that glucose was relatively stable throughout. Another diagram on the same subjects demonstrates an injection of insulin or IV infusion of 20-I use of insulin. You see fatty acids in the blood go down, ketones go sharply down. So you see a lot of that ketogenesis and fat mobilization for fuel is really a function of insulin suppression. I think that's really important to know and that has implications for sort of other things like do exogenous ketones elevate insulin and so if you take exogenous ketones will it promote a decrease in your own endogenous

ketone production and I think it's really important to understand what's going on the deliver and what's going on the muscle and what's going on in the brain when you're delivering exogenous ketones, which we think have many therapeutic applications and everyday applications. So that's, I've been focusing a lot sort of on some personal studies on that now and also in the lab. We're looking at that. So let's get into, we got a couple questions around genes. The first one is very broad. It says, what genes are not good for keto?

They're EEG, for example, FTO. I'm wondering if this is around maybe like the P-Pars and FTO, and I think some people have talked about this and how they handle saturated fat and fats in the diet and things like that. Are you aware of any of this literature? Thank you for listening to today's Sneak Peak AMA episode of The Drive.

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