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episode #149

Interview with Dr. Dominic D’Agostino: Exogenous Ketones, Advantages of Ketosis and Becoming a Fat Burning Machine!

May 17, 2022 in Podcast


This week I interviewed research scientist and professor Dr. Dominic D'Agostino! We discussed all about exogenous ketones, how to achieve metabolic flexibility along with: - Intermittent Ketosis - Advantages and Disadvantages of Extended Fasts - Best Ways to Build Muscle - Ways to suppress hunger and his one tip to get your body back!

0 (1s): Coming up on the get lean, eat clean podcast 1 (4s): For about three days a week. I really move heavyweight. So I'll do like a pressing movement and then a pull movement and a leg movement. And it's very easy to maintain muscle once you've built it. But if you're, if you're in a situation where you want to build muscle, that's going to, you're going to have to put more time and effort into the gym, probably up to three hours a week and then bump up your protein and your total calories. And then I just knew when I was younger, all I had to do is get enough protein, bump up my calories a little bit and lift heavy weights, and then the muscle muscle stuff on, you know, I added muscle over time. 0 (43s): Hello and welcome to the get lean eat clean podcast. I'm Brian grin, and I'm here to give you actionable tips to get your body back to what it once was five, 10, even 15 years ago each week. I'll give you an in-depth interview with a health expert from around the world to cut through the fluff and get you long-term sustainable results. This week I interviewed research scientist and professor Dr. Dominic D'Agostino. We discussed all about exogenous ketones, how to achieve metabolic flexibility along with intermittent ketosis advantages, disadvantages of extended fast, best ways to build muscle ways to suppress hunger and is one tip to get your body back to what it once was. 0 (1m 28s): This was a hard hitting episode with Dr. Dominick, lots of great tips and info that you can apply in your life. I really enjoyed interviewing him. Thanks so much for listening and enjoy the show. All right. Welcome to the get lean eat clean podcast. My name is Brian grin and I have Dr. Dominic D'Agostino on. Welcome to the show. 1 (1m 48s): Thanks for having me, Brian. I appreciate it. 0 (1m 50s): Yeah. Coming from sunny, Florida, I'm definitely jealous here in Chicago. 1 (1m 57s): Yeah, well it's, it was sunny yesterday. It's a little bit cloudy today, but most days are pretty sunny here. That's why we're the sunshine state? 0 (2m 3s): Have you been there most of your life? 1 (2m 6s): No, I never thought I'd live in Florida. Actually. I grew up in the Northeast New Jersey, went to Rutgers university for undergrad and PhD, and then went to Ohio for a short fellowship training before moving to Florida in 2006. So my wife and I love it here. You know, we got water on either side of the state. We got pond too. It's like, you know, we like to be by water. We like this time of year was pretty nice too. A winner's nice to kind of miss the seasons of, 0 (2m 37s): I will say the seasons are nice because you do it. It makes you appreciate when you get some nice weather. If it's not a every day or although you got some warm, you got really hot, hot summers, but I'm sure you're used to that now. 1 (2m 51s): It's not that bad. You know, I talk to my parents quite often in New Jersey and they're like in the mid nineties and it'll be nineties here, but then it up. And then it dumps rain later in the afternoon and it cools off like 20 degrees. And that's when I go outside and do like yard work and stuff at the end of the day. Usually I kinda like that pattern. So it's like steamy. Well, I don't like humidity, but it gets steamy during the day and then cools off pretty much every day. 0 (3m 16s): Yeah. Yeah. I would take that over 20 below. Well, why don't we tell them, why don't you tell the audience a little bit about your background? I know you're a retired research scientist professor at U S USF, right? Yep. Yeah. Maybe give him a little bit of background, how you got into the field that you got into. 1 (3m 36s): Okay. Well, I was always very much into like working out and fitness and everything, and I majored in nutrition as an undergraduate at Rutgers university in New Jersey. And then as I kind of went down the nutrition path, I didn't see a whole lot of opportunities, I guess you would say. And then, so I made a double majored in biology. And during my junior year, I started doing research in a lab at the Robert Wood Johnson medical school. And that lab was like physiology and neuroscience. So I got pulled into neuroscience as the nineties or the decade of the brain. 1 (4m 17s): And it was, I was very interested in neuroscience too. And I did my PhD in neuroscience and physiology, neural control of autonomic regulation. So like what controls our breathing like the brainstem mechanism mechanisms that control breathing and also sympathetic tone. The C one region of the brain stem actually controls our heart rate and sympathetic activity. So I was very interested in that. And then I was funded by the department of defense for my post-doctoral training to develop methods, to enhance in particular Navy seal operators that use a specialized equipment called a rebreather developing protocols and, and technologies. 1 (5m 1s): I guess you could say that would allow them to stay under water longer, to be safer and to enhance performance in these extreme environments. So our research is really about, you know, developing nutritional supplemental protocols to enhance the warfighter in extreme environments. Our, our lab has all these environmental chambers to create extreme environments. And then we test things and we break things and, you know, we figure out what doesn't work and what does work. And then we track the stuff that does work into human applications. 0 (5m 33s): What was the biggest thing in the breakthrough that you found from doing that research? 1 (5m 38s): Well, I focused like mostly on drugs, I'm in a pharmacology department, but then as I progressed through, you know, testing different drugs for anti-seizure effects, cause oxygen toxicity pretty seizures discovered the ketogenic diet. And then the kid had genic diet was actually used drugs for seizures fail. So I became interested in using this high fat diet, although the military was like, no fat will give everybody a high cholesterol and they'll die of a heart attack. So they asked me to develop a ketogenic diet in a drug, and then we developed different technologies, ketone technologies, like ketone esters, and then ketone salts. 1 (6m 18s): So I was kind of the one for better, for worse to bring exogenous ketones to the market. And they definitely do have applications. I believe in many ways, they're kind of oversold and over-hyped, but I can tell you as a researcher that they definitely have neuroprotective applications and wide variety of things. So the, the main breakthrough, I think, which basically changed the trajectory of my career was testing exogenous ketones as an anti-seizure neuroprotective effect. And this is 2010 and it worked way better than any anticonvulsant drug that we had ever tested. 1 (7m 1s): So it was remarkable and we published that it was like a 600% protection against seizures, under five atmospheres of oxygen, which was like super high. And, and yeah, to my knowledge, no drug can, can replicate this. And it was kind of interesting because it's something that you consume orally and then it elevates a bio identical molecules that our body makes, but we just have to fast for a week to elevate it to that level. Whereas if we take a drug like supplement, it can elevate it within like 20 to 30 minutes. So we administer these compounds and then, you know, we did tons of animal studies and now we're doing human clinical trials. 1 (7m 44s): So, and so that was sort of like the breakthrough that kind of maybe put me on the map and I'm a big fan of the ketogenic diet too. So I've been following the diets since 2009 and, and a modified version of the diet that's higher in protein. So we can talk a little bit about that, but it's been a fun area of research. I'll I'll say that for sure. 0 (8m 5s): Yeah, I can, I can imagine with ketone supplementation, like you mentioned, it's, you know, everyone catches on, there's a lot of supplements out there that are probably junk. What, what I know you've backed a few different companies. What w what sets them apart? And is this something that like, for example, like, do you take this on a daily basis or do you do this just on certain occasions? 1 (8m 30s): Yeah. Good question. I don't believe like everybody needs to be taken ketone supplements and, you know, I, I guess I have, well, I was going to say I have patents, but the university has patents that I am the inventor on, and they own the technology. Then they license it to different companies. And I, I prefer there's an exogenous ketone supplement on the market called keto start by audacious nutrition. I mean, we have done a lot of work on ketone esters, and that's one class of ketone supplements that continue to taste awful. What we have found out is that higher is not better. So if you can just boost your ketones by like 0.5 to one or 1.5 millimolar, which you can easily achieve with an electrolyte ketone salt. 1 (9m 18s): So an electrolytes would be sodium potassium, calcium, magnesium, similar to the product element that Rob Wolf has. So I use a product called keto start, which has the same electrolytes, but those electrolytes are bound to beta hydroxybutyrate. So, first thing in the morning, I just take like a third of a pack of that. And it's like, boom. You know, it's like the ketones and electrolyte hits your brain and it's like, ready to go. Yeah. Yeah. So, you know, not too many things you can feel creatine, you can feel, you know, after about a week or so. You know, I ate a lot of red meat, so it's very subtle caffeine, you know, there's not a whole lot of things you could say, Hey, you can take this and you can feel it. So ketones are one of those things, but we're at the very nascent area of research on this. 1 (10m 3s): And when I was taking exercise physiology, which is probably the only class I got to see in an undergrad, I, I, and then the final exam, it was like naming ergogenic aid that is proven to enhance performance or something. And I wrote this whole, like thing on creatine monohydrate and it had got like a big X through, it said, no, there's like no studies to back this up. And that was, that was 1995, I think. So the studies were just coming out there were super compelling. And I think we're at like the 1995 stage of ketones here. Oh, I think ketones will kind of be the next, you know, it'll take a while, but they definitely, you know, it's, it's a form of energy. 1 (10m 46s): So when you consume it, it's giving your body and a form of energy. That's not, you know, elevating glucose and it's having some remarkable signaling effects. So right before getting on my student is actually extracting histones. So we're looking at the epigenetic effects. So ketones, beta hydroxybutyrate, and maybe a pseudo acetate kick on epigenetic programs that can enhance genes associated with learning and neurogenesis. And we're applying this to disease states, but then again, they're activating enzymes and systems that could help the everyday person too. So that's a big thrust of what we're doing now, looking at the signaling and epigenetic effects of ketones. 0 (11m 32s): Ah, very cool. And I've gotten into this a little bit, myself like yourself on, into fasting, into red meat. And I noticed some of your workouts, you got some good compound lifts that you do these micro workouts. And maybe we can touch on that. I started, I was like, as it got, I've been probably eating. I don't really like count, count carbs, or even count calories, but I've been eating pretty low carb for a while now. And I was like, I got to start testing and seeing if I'm getting, you know, some ketones in my blood. And I know you do, there's a few different ways to measure it. I, I use, I've been using keto mojo with the blood, with blood. And it, it is interesting, obviously when you get your insulin levels down, your glucose down, your ketones sort of it is the inverse effect, is this correct? 1 (12m 18s): Yeah. Yeah. That's a good way to describe there's an inverse relationship to ketones and glucose, especially if your glucose is tends to be high, you know, and then your glucose will go down to a certain level and then your ketones will kind of go to a certain level too. So yeah, I, I actually use a breath ketone meter called Biosense. So that's one of them on the market. I like Kito mojo too, for the blood meter. W most of the work that we've tested has been the Abbott precision Xtra device or the freestyle, but we also do biological assays. We also take blood and do mass spec on it to measure ketones. 1 (12m 60s): If we want to look at CDOT, acetate and acetone, sometimes we'll look at all three ketones in the blood that is tricky to do. You have to use a substance called sodium Bora deuteride, which explodes if you, if you stick around it too much. So sometimes we do experiments where we need to measure all beta hydroxy, theatery CDOT, acetate, and acetone, which interestingly their commercial devices, blood urine, and breath, respectively for beta hydroxybutyrate, CFS, Tate, and acetone. And they're all very useful under certain conditions. And people say blood is the gold standard, but I think for this community, when it comes to fat burning, what I, I know actually when it comes to seizure control too, when parents contact me and they said, you know, they don't want to prick their kid's finger breath. 1 (13m 48s): Acetone correlates probably much better with seizure control than blood. This is some of our early work actually led me to look at acetone, but you can be in a situation. I think the important thing for the audience here is that you can be in a situation where your blood beta hydroxybutyrate stays low, but your breath acetone is high. And that's because athletes tend to dispose of beta-hydroxybutyrate in tissues because you're using it as fuel. Whereas, and it has to do with the redox state of the mitochondria, perhaps in NAD levels and things like that. But the important thing is that if you have high acetone in breath, you are like a fat burning machine. 1 (14m 31s): So all those carbons from the acetone, it would basically from the fat, like if you're fasting the fat from your body, and if you're eating a low carb, high fat, that's, you know, a combination of fat from your body and that, so, so your, your acetone is really probably the most reliable marker for fat oxidation. And I guess put another way if your acetone is elevated, you for sure are in a state of ketosis and you're burning a lot of fat. So, and it's easy to do in the long run. It's going to save you money, just puffing into a device and getting a number, which is the doses are pretty accurate now. So they weren't like that 10 years ago. And it took me a while to warm up to the Biosense device cause I was blowing into it. 1 (15m 16s): And I was like, guys, it's not really, you know, you told me it was going to correlate with beta hydroxy iterate and it was not. So I didn't, I kind of lost enthusiasm for it. But then I started doing a little more research. Peter Attia friend of mine was doing some research and other people. And we realized that if you're in a calorie deficit or you're fasting, the acetone gets really high, but beta hydroxybutyrate tends to trend a little bit lower. And that's because your body's kind of using it for fuel and disposing it within the keto adapted state. But it was very, I guess, rewarding to basically see high ketones on the breath meter. And I knew for a fact that I was in a high fat burning state, like you can taste ketones on your breath. 1 (15m 57s): Like if there's just a feeling that you have, but my beta hydroxybutyrate was staying kind of low. So long story short after a lot of different testing, the breath acetone devices, pretty pretty remarkable. It's kind of won me over over the last couple of years. 0 (16m 12s): Okay. So I'd have to try it. So there's I guess a few ways to do it, right? Blood breath and urine and they're, and they're measuring the like three different ways that you can produce ketones. Does that sound right? 1 (16m 27s): Yup. The blood measures primarily beta hydroxybutyrate and that's kind of the, the form of ketones. That's highest in circulation and beta hydroxybutyrate needs to be converted back to a CDOT acetate to be used as an energy source. And it's usually in a ratio of like three to one or four to one beta-hydroxybutyrate to a CDOs state and then a CDOT acetate can spontaneously decarboxylate to acetone. And this is pretty it's, you know, about 20% all the time. And then the acetone then becomes a very good surrogate, a very good marker for fat oxidation. And it seems to be, it doesn't fluctuate around that much because acetone is a polar molecule, but it's also slightly non-polar and can dissolve in tissues and it gets into our lungs and then we blow it out. 1 (17m 20s): So it's a volatile, we blow it out, but it tends to distribute throughout the body. So it tends to be a more stable marker. And when you're in a very high fat oxidation state, it's going to be very high where sometimes beta-hydroxybutyrate could be low and it's almost like a false, you know, negative it's it's like, it's, it's telling you even you are in a fat burning state, but some people are like, I'm checking my ketones and I'm not. And they'll tell me what they're eating or what they're doing. And it's like, no, you should be in ketosis. But their acetone is really high and was like, no, you are in a very high, fat burning mode. And I think that's what we want as a community. We want to make sure we're in a, we're burning fat for fuel for the majority of people. I mean, I work in the clinical world and I think it's useful beta hydroxybutyrate in some contexts, but come to find out breath, acetone would probably correlates better with seizure control than blood or even urine. 0 (18m 11s): Okay. That's good to know, because I think when I first started measuring my ketones has a cat that seems so low. Like I've been, you know, I, I, you know, I'm a pretty good, I don't like over fast, but I, I tend to fast quite a bit through the day and I have my meals towards the end of the day and I'm like, gosh, I thought it would be. And so that could explain it, like you mentioned, maybe using the breath and the blood is the best way, 1 (18m 34s): You know, you're, it's okay to, I communicate with quite a few neurologists epileptologists and their dieticians that used a urine and kids mostly because you don't have to prick the finger, but they have told me, Hey, the urine is better than the blood in the urine is a CDOT acetate. And which would correlate better with acetone, but urines messy. And it's, it's very, it's not very quantitative. It's like semi quantitative, but, but like a breath acetone device, like, like the Biosense there's other devices out there to the bias tends to be more accurate. It goes like zero to 40 and then 10 Ace's it's a units will correlate kind of to one milimole beta hydraulic hydroxy battery. 1 (19m 18s): But if you're in a calorie deficit, there tends to be a decoupling of that. Whereas you could have like 30 or 40 ACEs and I can max out this device. And then my blood beta hydroxybutyrate is only like one or two, you know, even in a very high fasted state. So from a day to day use ketones can fluctuate a lot. So measuring them, especially when you're starting a diet three or four times a day, which is pretty easy to do when you're blowing and not having to have a pin cushion for your finger yeah. Is very easy. And cost-effective, and then there's an app associated with the Biosense device that is kind of cool. 1 (19m 58s): Cause you can like compare it with your, you can track a meal and you can see what it does in response to a meal or if you're fasting and the apps very useful too. So me, it's a very user friendly, but it's also permeating the clinical world. So it's a class one FDA device used clinically, but I think the company is trying to, you know, get more general users on board to, as they're doing a lot of clinical research with it. 0 (20m 26s): Yeah. And I'm sure people who are listening, who have never done any of this, this is probably like a foreign language a little bit to them, but maybe, maybe tell the audience what would be the advantages of doing this. And is this something I know you've talked a little bit about like metabolic flexibility is that the ultimate goal is to sort of switch and throughout fuel sources, glucose and, and you know, ketones. 1 (20m 52s): Yeah. Good question. It is the, you know, the only way we're going to produce ketones is if we're burning fat as an energy source. So the traditional standard American diet, you know, basically recommend eating carbohydrates in multiple meals throughout the day. And in this way you will never really produce any ketones. And I think you could probably make the statement. It's very UN some people who make the statement, it's unnatural to be in ketosis all the time. And I tend to agree with that. Although I tend to be in a state of mild ketosis, although, and then we also have, you know, there's people who have epilepsy or other disorders who have been on a ketogenic diet for 30 years nonstop and they, and they're doing fantastic. 1 (21m 41s): So I'm not sure it's dangerous, but I don't, I don't think it's sort of something you'd find in nature all the time. But in nature there was definitely limited carbohydrate availability. So carb restriction is a natural thing to do. And then there would be intermittent periods of food availability. So not fasting would be very unnatural to do that. So I tend to, when I do intermittent fasting or time-restricted feeding, which is the term used in science, I tend to lose too much weight. Cause my metabolism is pretty fast. So like today I'm doing it actually. I've not done it in about three or four weeks because I've been trying to gain some weight back. 1 (22m 25s): Yeah. Cause I was traveling, then I get my wife and I get COVID and it just like didn't eat anything. And although we bounce back quick and it's just like I realized, well, my weight's been slipping over the years, so I'm trying to build my weight back up, which involves eating breakfast really. And so I've been doing that for a while, but I do, if I did intermittent fasting all the time, I feel that it would take away some of the benefits. So I just do it, you know, just occasionally and, and that helps promote metabolic flexibility. So whenever you go without food for a while, you're tapping into your fat derived adipose stores and you're using fat and you're going to be making ketones. So bumping your ketone levels up a couple of times a month would be a very simple thing you could do to promote metabolic flexibility and to improve pretty much every biomarker that is important. 1 (23m 17s): And that could be, you know, your glucose, your hemoglobin A1C, your insulin, your blood pressure, all these things and your triglycerides go down, all these things improve remarkably simply by, you know, periodically like carb restriction and then periodically doing, if you don't like carb restriction, you could do intermittent fasting. 0 (23m 35s): Yeah. And I, I noticed you posted about doing a 72 hour, like modified fast. Maybe explain that to the audience. I mean, this is maybe something that you you've probably built up to this point, right? Like I always recommend sort of, you've got to ease your way into fasting and once you've been doing it for awhile, then you can maybe do some longer fasts. Was that something that you did? 1 (23m 59s): Yeah. In early days I got very intrigued by the work of Dr. George Cahill and he was still alive when we connected years ago and Dr. Theater in Italy and Dr. Richard Veech and, and they had done some, some seminal work on fasting and starvation. And I became interested in like, you know, fasting for seven days and as a way to elevate ketones and sustain it. And this is kind of when I was tinkering with exogenous ketones too. And I was testing them under different, certain, certain conditions. So I did a lot of fasting over the years, going back to like 2009 or 10 and seven day fast and five day fast suppressed my hormones so that my testosterone goes through the floor. 1 (24m 44s): You know, I feel that it's shutting down on my metabolism, body temperature drops a little bit. It's great. If you want to fast before, like breath, whole diving, that will, it makes your metabolism so efficient by turning down your metabolic engine, your sympathetic nervous system goes down, parasympathetic goes up, heart rate goes down, all these things kind of go down and it allows you to hold your breath for a long time. So I was interested in doing that, but a three-day fast can put your body into a metabolic state by suppressing insulin so much, it becomes hard to measure. And then your ketones at about three days, your ketones come up to the level of your glucose. 1 (25m 25s): And we call that a glucose ketone index of one, meaning that glucose comes down to about like 3.5, three or three point. And Nan ketones will come up to beta. Hydroxybutyrate will come up to about three or 3.5. And in millimolar concentrations, that's a glucose ketone index one. And I would suspect, although we have not measured autophagy in humans, we tend to look at the autophagosome and LC three and things in mice. My, my, my best guess is that when you achieve a glucose ketone index of one and hold that for about 24 hours, you're kicking on a lot of autophagy, beneficial autophagy and stem cell production. 1 (26m 8s): And then, you know, a lot of benefits come from doing that. Although if you go beyond three days, then you start to see suppression of hormones and things like that. And it takes a while for that to come back, it takes like an equal amount of time or a week or two. And then I also noticed my strength will dip, not at the end of the fast, but the days following, I noticed a measurable decrease in my strength with a five day or seven day fast, not at the end of the fast, but in the period after it's almost like it takes your body some time to recover. So long story short three-day fast seemed to be the sweet spot for me. And I do them occasionally every couple months as like a metabolic reset. 1 (26m 48s): And it's also very, you know, if, if someone wants to, and I've talked about this with like Tim Ferriss and other names once to purge your body of potentially precancerous cells, or kind of reset their insulin sensitivity and, you know, stimulate autophagy, maybe promote longevity, although the science needs to catch up with that statement, they could do a three-day fast, you know, every, and, and if you are overweight and you have some, some weight to lose, then you can extend that to five days or maybe in seven days. And people that are really heavy have communicated with me and they they're fine with like 10 days or 14 days not advocating that, but the more fat you have, the easier it would be to fast. 0 (27m 32s): Yeah. And I was going to say that, so that was your sort of self you found the sweet spot, at least for you was three days. And obviously you're a fairly lean and I don't, you know, I don't know what your body fat percentage is, but I'm sure it's pretty solid, pretty solid. And, and, but for some people, like, I know I had Dr. Jason Fung on and we'd talked about, you know, they do do some extended fast beyond that for maybe people who, who need it, like you said, are, you know, morbidly overweight. 1 (28m 1s): Yeah. Yeah. I'm definitely not trying to lose fat. My weight has slipped over the years. I used to maintain like 2 30, 2 40 for many, or that it was really into lifting. Now. I stay like two 15 ish to 10. We kind of tall, like over six foot. So, so at that weight, like I'm not big, like I kind of have a normal frame very much into work working now, although probably don't lift weights more than an hour a week, total time tend to do a lot of activities outside, heavy work activities, lifting a lot of things, cutting logs, moving, shoveling poop from the cows, stuff like that. And yeah, like, you know, kind of heavy work and that's like my active recovery and cardio. 1 (28m 47s): And then for about three days a week, I really move heavyweight. So I'll do like a pressing movement and then a pool movement and a leg movement. And it's very easy to maintain muscle once you've built it. But if you're, if you're in a situation where you want to build muscle, that's going to, you're going to have to put more time and effort into the gym, probably up to three hours a week and then bump up your protein and your total calories. And then I just knew when I was younger, all I had to do is get enough protein, bump up my calories a little bit and lift heavy weights. And then the muscle muscle stuck on, you know, I added muscle over time. 1 (29m 27s): So 0 (29m 28s): Yeah. I noticed your, I love how you do these micro workouts, a buddy of mine, Brad Kearns talks a lot about that and 1 (29m 36s): Yeah, he's a great guy. 0 (29m 38s): Yeah. Yeah. He's great. And I love that idea. I just think that, and I'm sure you do too, obviously a 15 minute workout. I mean, you can't do that and like, you know, you sort of get rid of the excuses, right? 1 (29m 53s): Yeah. Yeah. Well, I have a chin up bar thing. That's not in my door now because clothes, but I just throw it up in the doorframe and between zoom meetings or virtual teaching or whatever, if I'm in my home office, I was just banging out a set of chins and get right back to it or do some pushups and things like that. If it's a day that I don't have time to work out or something, you're getting to the gym. 0 (30m 14s): Right. So 1 (30m 15s): I don't go to a gym. I go to the barn, which has weights in it and that's my gym. So I dunno to the gym in many years. 0 (30m 21s): Yeah, no, that's nice. And I know, so you do a push pull and a leg split, is that right? 1 (30m 29s): Yeah. It's very dependent upon like my routine too. Sometimes I will do yeah. Push pull together, but usually like a push workout, a pool workout and a leg workout. And then maybe I'll add an accessory exercise at all do in between those sets. And then I rotate the exercises. So the last time I squatted, so the next time for legs, I'll do a hex bar deadlift. And then on back day, instead of doing like that list, I'll do like a banner of a row, like a one-armed row or something like that. So, but it's like, I, I like put full attention and focus into like one exercise. 1 (31m 9s): And then that becomes like all day, if I know I'm going to work out, it'll be like, you know, 0 (31m 17s): Do, do fast 1 (31m 17s): 14 for 8, 3 15 for eight. So it's like, I'll have this certain rep range and weight that I want to do. And that'll be my goal for the day. And I'll lock that thought in, in my mind and I'll be, I'll have that. Like when I was younger, I did periodization. So I knew exactly what I was going to do. I used a periodization template for power lifting and I would like, look at it the night before I went to bed, I would sleep on it. And then it would be like, totally amped up and ready to do it. Once I hit the gym, like it was a lifting, very mental for me too. And I think it's kind of an escape in many ways, but 0 (31m 54s): Yeah. Do you do your workouts in a, in a facet state? I know you're obviously now you're trying to bulk up, so you're having breakfast and stuff. So probably right now you're not, but is that something that you mess around with? 1 (32m 6s): Yeah, I get that question a lot in, I do not like to work out on a full stomach that's for sure. So typically it'll be, you know, four to eight hours after I've eaten. And if it's like a dead lift or squat workout, like sometimes there'll be 12 hours, you know, sometimes it will be completely fasted, but for, for pressing movements, I like to have some food and sodium and water in me. And that I feel a little bit fuller. I get more of a, like a cushion rebound effect, you know, for that. Whereas if I'm a little bit energy depleted and flat, then I don't have that pressing power, but my leg strength and back strength seems to not be affected if I'm in a fasted state. 0 (32m 51s): And yeah, I know you talk a little bit about this intermittent ketosis and maybe explain to individuals what, what this is you might've already mentioned, how maybe you just take a, a certain period during a month and get into ketosis. And obviously that has benefits in its own. Is that what you mean by intermittent ketosis? 1 (33m 13s): Yeah, I would say for me personally, and it has to do in part because I am a researcher, a ketogenic diet researcher, and an exogenous ketones, and we also do calorie restriction fasting and things like that. I stay in some state of ketosis pretty much all the time, but it can fluctuate from very low to a little bit higher if I'm testing something. But I think for the majority of people, it's not very practical to beat on a ketogenic diet all the time. I mean, you probably find it easy to do low carb, but low carb will not necessarily put you in a state of ketosis. We do know experimentally, and this goes beyond animal models that having elevated beta hydroxybutyrate, even to one millimolar, you know, or breath acetone 10 or 20 ACEs on the, on the breath meter can give you additional benefits. 1 (34m 8s): So there are like beta hydroxybutyrate has anti-inflammatory effect. It's almost like taking an end state, you know, once your ketones get up into that, like, you know, one to two to three range as remarkable anti inflammatory activity, we are studying epigenetic effects. So it's turning on gene transcription of things that can help, you know, neurological repair learning and memory BDNF brain-derived neurotrophic factor. So these are the things we study in the lab and you know, the more research I do in the lab and see the benefits in animal models. And I cautiously always say, animal models are informative, but not always predictive of what's going to happen in humans. 1 (34m 52s): But when you put animals on a ketogenic diet and you implant tumors and you see after a certain amount of days, like all the animals on a standard diet have died because of tumor hypergrowth. Whereas the tumors are suppressed and growing slower and a ketogenic diet, or you see, you know, they have a neurological disease and they do so much better on a ketogenic diet that tends to influence your decisions on dietary preference. You know, the more you do this kind of research, even though it's a 0 (35m 23s): Well you're at a day in day out. So I don't, I can see while, you know, you make, you make it a lifestyle, you know, you make it a part of your lifestyle, but, but what, what carbs, if when you do have carbs, if you do, I have, I'm assuming you have them from time to time. What carbs do you prefer? 1 (35m 42s): Yeah, last night, you know, I went, this is the longest time I actually went without blueberries and just the winery next door to us, it's having a blueberry festival this weekend. So actually we, my wife bought blueberries yesterday, but I went a week without, so every night I do like typically three meals, like Akido high-protein keto meal in the morning that I didn't eat yet. And then lunch, I might, I might skip lunch, but otherwise I might have high protein keto meal. So keto, keto, low carb. So my dinner would be low carb. And the dinner usually is we love Brussels sprouts, asparagus broccoli, sometimes cauliflower, mashed cauliflower mash. 1 (36m 24s): And then we have some kind of meat or fish. A lot of, I love fish, but we have beef. We live in like, I mean, we have cows, we don't see our own cows, but we have a lot of access to completely grassfed meat around us. I've been eating a lot of Turkey. We have farms near us that have Turkey, eggs, and turkeys and things like that. So typically meat, a big salad. And then for, I do tend to snack a lot at night. And I noticed that eating at night is not good, but I've always done this. That's how I gained weight. When I was younger, I would just come home from school and be like 10 o'clock at night to 11. And it would just make this massive bowl of oatmeal and throw in tons of chocolate protein powder and just like eat it, like just, you know, right before bed, every day. 1 (37m 9s): And that's that always worked for me. I always slept great, but now I tend to try to get my food and majority of food in probably like, you know, throughout the earlier hours. But I snack pretty much every night and I have like ketogenic ice cream. There's a killer Creamery is very good. Rebel ice cream. I think I've heard, I make like a moose where I take sour cream and I put like cocoa powder in it and some Stevia and then blueberries and then cinnamon. And then I stir it all up and then I like eat it really slow. And we usually 0 (37m 45s): Have to get that recipe from you. 1 (37m 47s): Yeah. It's like so easy to make. And it's just, you know, we get a good quality sour cream we buy and then a good quality, like dark chocolate, bacon cocoa, not too much. Cause I could have a little bit of caffeine in it. I try to avoid caffeine after about 1:00 PM and then some wild blueberries, like I put in it. And, but it, it's not an insignificant amount of blueberries. It's like about a cup, which is like 30 grams of carbs. But the wild it's like almost one third fiber. So it comes out to only like 20 grams of net carbs. And you know, I wake up and then it's your it's in sour cream. And I have no, I wear a continuous glucose monitor and it's like completely flat when I do that. 1 (38m 31s): And sometimes I throw in some collagen powder and stuff too, or some protein powder. And then I eat that for my snack at night. It's very satiating. I have good stable, but low glucose throughout the night. And you know, I've been doing, it's almost a way I'm almost like fat and carved back feeding. Like throughout the day I get so busy and so immersed into my work that I under eat. So I have to make up for the calories and I'm gaining or losing weight is all about a calorie deficit. So, you know, I do believe the calories matter and I think the type of food, we matter to it type of food. 1 (39m 11s): We matters tremendously, but if you want to get lean and you want to gain muscle, lose fat or build, you really have to pay attention to total calories and then adjust based upon, you know, weight stability. If you keep your track, your calories and after two weeks you haven't gained or lost weight, then you adjust it for me. What I do is like, I'll do, if I want to lose weight, I do a 20% reduction in calories only like two or three times a week. And then the weight comes off and I start seeing like abs and start getting like veins. And just after doing that for like a couple of weeks and if I want to gain, I usually do it by titrating in more protein from like 1.5 grams per kilogram to two grams per kilogram. 1 (39m 58s): So me I'm a hundred kilograms, so it's like 200 grams of protein a day. I'll bump it up if I want to gain and put on some muscle. 0 (40m 6s): Okay. Yeah. That's this is, I love hearing people's routines and what they do. I'm, I'm similar. I like to back load carbs. And if I have meals in the middle of the day, mainly protein and some fat, are you using a lot of, like, I think I keep hearing about, you know, C8 MCT oil, what, what are your thoughts around that? And you know, I, I had a conversation with Melanie Avalon and she's like, oh, she's like, this is like the godsend. You know, if you sprinkle this on and I'm curious to know what your thoughts about, cause you see it, you can start in the seat in the market all the time. 1 (40m 42s): Yeah. Well I guess, you know, I said that I'm like fast to now, but I guess to be honest, I did have some calories in the form of, I have a third of the pack of Cheetos start and then I have that with some creatine and Seattle, Seattle L-carnitine. So I'll have that in the morning. And then bam, I can feel that then I make my coffee, walk the dogs, go outside, let the cows out, do that, get like fresh air sunshine. And then when I come back, my, after my coffee brewed, I add an MTT based powder actually has some other things in it. It's called Quito brains. It has like lion's mane, alpha GPC and C eight MCT, which is caprylic triglyceride. 1 (41m 25s): And just simply consuming that will bump up your ketones. And yeah, I'm a big fan of, of medium chain triglycerides. We have done quite a bit of work with that. We've published quite a bit of work with medium chain triglycerides. We find that when you take MCTs and add it to a ketone Ester and you take MCTs and add it to a ketone salt and use those combinations in our research, our animal research, we always get much better results because you're stimulating your, your body's own ketogenesis process with MCTs. So that's an important concept while you're delivering exogenous ketones, which will elevate ketones in and of themselves, but you're delivering exogenous ketones while you're stimulating your own. 1 (42m 10s): And then the fat from the MCT extends the pharmacokinetic profile. So your ketones stay elevated longer. 0 (42m 18s): And do you find that like, I mean, you gotta be riding high in the morning with, you know, if I had CA I find that like when I'm, you know, in a Kita G you know, like in ketosis, there's this say, it's almost like a high, a little bit, you know, you feel you could feel it. And is this something that I, I lost where I was going to ask, but is this something that you feel like you do before workouts? Or is this just something you do in the morning? 1 (42m 44s): It's more for like a mental focus and it allows me to decrease the chatter in my brain and you know, maybe I have some, 0 (42m 55s): It suppresses hunger. I'm sorry. That's what I was going to ask. Yeah, 1 (42m 58s): Yeah, yeah, it does. Yeah. Like I am like, totally not thinking about food. I'm not hungry now. And you know, if I would have eaten breakfast three hours ago, I feel like I'd probably be more hungry now. I skipped breakfast and just had a little bit of MCT from the keto brain's product, you know, a pinch of ketone salts for the electrolytes and the little bumping ketones. And yeah, I feel, you know, this is, this is the mental state, where am, I'm not overly hyper, but I have like a calm energy, I guess. 0 (43m 33s): 'cause, I think that's what like, would be very applicable for a lot of people eventually getting to that point where, because really, and I find this too, you know, you've been doing this for so long that like when you're suppressing hunger through other, you know, through these ways, like you're talking about, I mean, that's key for a lot of people. If they're looking to, you know, lose inches and, you know, put on some muscle per se. And I don't know, I just think sometimes that I've been doing it for so long that I have to almost force myself to eat. Like you said, you wanted to put on weight. So now you're eating three times a day, but yeah, I think it's a good tool, but how long do you think it takes to get someone who's maybe gone from the standard American diet into this, you know, great metabolic, flexible state of being able to use fat for energy? 1 (44m 22s): That's a good question. I'm glad you brought it up because we find in our scientific research, we have a registered clinical trial looking at low carb ketogenic diets using continuous glucose monitoring. We're using the level's health app with Abbott Libris device, which is a CGM. I use a Dexcom G six. So the, the levels app works for both. What, what we find in patients is that it's best to transition them into a good agentic diet over about four to six weeks, we have better adherence, better compliance. And then you have a nice transition into this metabolic state instead of, you know, if they go from standard American diet, the ketogenic diet in one day, you get the keto flu, your glucose and insulin go down, and then you're not really making ketones yet. 1 (45m 16s): That's when like exotic ketones can help because it helps suppress your appetite. And then it gives your brain energy. So you don't get, you know, the brain fog or the keto flu. And then actually just getting ketones into your system helps to ramp up catalytic, keto, adaptive processes. And then, you know, your, your body will, and it doesn't inhibit your own ketone production unless you take large doses of the ketone Ester, which I wouldn't recommend, but you know, Nat to train your metabolism after about four to six weeks is probably the best way to do it. If you're listening to this and you're far from a ketogenic diet, and you're getting that standard American 2, 3, 400 grams of carbs a day, that would be the way to do it transition after about four weeks. 0 (45m 57s): So when you say transition after four weeks, you mean gradually, maybe lower carbs sort of changed through your macro count? Yeah. 1 (46m 5s): Yeah. If you're at 300 grams of carbs a day, knock it down to one 50, no sugar, very little starch, you know, maybe go from like, if you're eating two or three potatoes a day down to just like one or half a potato, and then eventually just transitioned into like, you know, veggies for think of carbs. It's just hot fiber. And you know, for me, I get high fiber fruits. I avoid like bananas and dates and dried fruit and things like that. But I get, you know, different types of berries, occasionally like an apple. And then we have grapefruit trees in the back. Sometimes I'll grab one of them are great. Fruits are very bitter though. So it's like, they almost have a very little CGM response. 1 (46m 47s): I love fruit and I probably have fruit pretty much every day, but it's all about the amount that you consume. Right. 0 (46m 53s): And, and I, and I know you, you saw the book uric acid, what was the drop acid? Oh yeah, 1 (47m 0s): Yeah, yeah. 0 (47m 3s): I had, I had doctor I didn't have, is that Perlmutter? I didn't have time. I had Dr. Richard Johnson on and he talked about you, you want to eat your fruits? You don't want to drink them. 1 (47m 14s): Yeah. Yeah. You know, that's a huge problem. And you know, growing up, we didn't know it that much. If you drank, I remember drinking like, you know, a quarter of orange juice and bringing like a quart of orange juice to school with and drinking that or apple juice. It's like basically liquid candy and it's yeah. I mean, the CGM responses to this are pretty scary and they look just like drinking any equal amount of Coke. So there's really no difference and interesting, you know, that's like should be intuitive, but for most people it's not, they think, oh, orange juice. I'm getting vitamin C, but you're delivering it with like an Ivy of sugar. Yeah. 0 (47m 53s): All right. Well, we're getting up on time. I'll ask you a question that I normally ask most of my guests. What, what would you recommend? You know, middle-aged, I mean, how old are you Dr. Dominick? I'm curious. 1 (48m 5s): I'll be 47 soon. Yeah. Yeah. Mid forties kind of pushing 50. I feel pretty good. I mean, I kind of feel my age creeping up with me, but I feel like I'm doing everything that I wouldn't do anything different, I guess you would say for, for a long time. 0 (48m 21s): And I, and I love that. I mean, you look great. I, my question was, what tip would you give someone getting up there? You know, I'm 41, so let's 40 plus. And they're trying to maybe get back to where they were in their thirties. W w what, maybe one tip would you give that individual because you're living it. So, 1 (48m 41s): Yeah. You know, what, what gets measured gets managed? You know, that term gets thrown around a lot and the entrepreneurial world, I guess. So I think I highly recommend people get blood work, to find out where they're at and then come up with a strategy to determine where they want to go. And then there's many tools out there to do that. We maintain a website, Quito nutrition, or G it's not all about the ketogenic diet. I mean, we have quite a few blogs about biomarkers, what needs to be tracked to optimize your metabolic health. So your, if you get your metabolic health tuned, that that will be leaps and bounds for enhancing your longevity, your energy and everything else. 1 (49m 27s): So focus on optimizing your metabolic health, but to do that, you need to be tracking, right? And there are different, different things that you should be tracking. So what I recommend is like, know what your fasting glucose is, know what your insulin is, your triglycerides, your H S CRP, which is something you can add that to standard blood work. Just tell your doctor, you know, and sometimes if you tell your doctor, Hey, I feel inflamed. And can I add this to it? And then usually your insurance will cover it if you do it like once a year. So your insulin triglycerides, hemoglobin A1C, fasting glucose, and your blood pressure, blood pressure is super important. 1 (50m 8s): It doesn't get talked about enough, you know, your blood pressure and know what elevates your blood pressure and what decreases the ketogenic diets are great for decreasing blood pressure. So track these things and optimize them. And then you're basically doing everything you can for London. 0 (50m 23s): No, I love that. I think if you don't know where you, you know, if you don't have a baseline, then you don't really know what you're looking to, you know, where you're looking to go. So that's great. Well, so when's it, where's the best place for people to find? Is it keto, nutrition.org? 1 (50m 39s): Yeah. Go there. And you'll find me on Instagram, Dominic D'Agostino Katie, I think. And then I'm on Twitter and Facebook, I guess, too. So you can find me there, but keto nutrition is kind of like our brand. We don't sell anything, but we do put out information and I have, you know, grad students and medical doctors help us with some of the articles on there. And we try to give information that's scientifically informative, but actionable to 0 (51m 7s): Love that. Love that. Well, I really appreciate you coming on the podcast. Tons of great tips. So thanks so much for coming on. 1 (51m 15s): I appreciate you having me, Brian. Thank you. 0 (51m 19s): Thanks for listening to the get lean clean podcast. I understand there are millions of other podcasts out there and you've chosen to listen to mine. And I appreciate that. Check out the show notes@briangrin.com for everything that was mentioned in this episode, feel free to subscribe to the podcast and share it with a friend or family member. That's looking to get their body back to what it once was. Thanks again, and have a great day.

Dr. Dominic D'Agostino

This week I interviewed research scientist and professor Dr. Dominic D'Agostino! We discussed all about exogenous ketones, how to achieve metabolic flexibility along with: - Intermittent Ketosis - Advantages and Disadvantages of Extended Fasts - Best Ways to Build Muscle - Ways to suppress hunger and his one tip to get your body back!


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