Mind Pump: Raw Fitness Truth - 320: Dom D'Agostino Interview- Leading Ketogenic Researcher

Episode Date: June 30, 2016

Sal, Adam & Justin interview Dr. Dominic “Dom” D’Agostino. Dom is a leading researcher studying the ketogenic diet. In the interview they go into Dom's work with Navy SEALS and his own experience using the ketogenic diet and how it has affected the results he experiences in the gym. Dom is an Assistant Professor in the Department of Molecular Pharmacology and Physiology at the University of South Florida Morsani College of Medicine, and a Senior Research Scientist at the Institute for Human and Machine Cognition (IHMC). Get MAPS Anywhere at www.mindpumpmedia.com. Please subscribe, rate and review this show! Each week the best reviewers are announced on the show and sent Mind Pump T-shirts!

If you want to pump your body and expand your mind, please only one place to go. Mind, hop, mind, hop with your hosts. Salda Stefano, Adam Schaefer, and Justin Andrews. To the hip hop. Hip into the hip, hip hop. Don't stop rocking to the bang, man. I don't know if there's a boogie-de-be. A bunch of energy because we know we're getting ready to hit the road in that town.

And we just had a pretty badass interview with you. Do you know we just talked to you're about to hear Coming up in this episode our interview with Dom Diagostino. This guy did say that more Italian, please Diagostino. Yeah, the whole thing. The other time we'll be telling super smart. Did you hear he can deadlift a crazy amount of sound like anybody?

Just tonight. He said he's a monster. He's way smarter and stronger than me. Yes, just tonight we're totally flirting with him off air, which we're trying to get him away. Wow, you know, sounds busy sometimes if you're ever in the area. Yeah. Your references were even more impactful.

Bro, the first. Well, there was a couple of times where I mentioned an article or something. You're gonna hear this. Well, there was a couple times where I mentioned an article or something. You're gonna hear this. So there's a couple times where I mentioned an article like, oh, I read this about the ketogenic diet and relationship to blah, blah, blah, blah, blah. Like I always do.

And Dom's like, oh, you must be talking about the New York Times article published in 2015 on December blah, blah, blah, by Dr. or someone's like, yeah, this motherfucker kills me at me. He did that. He beat me up. He beat me up. He beat me up. He beat me up. He beat me up. on December, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah I was most impressed, like holy shit. It's okay though, he validated your references. It's just like, whoa, he's involved with these people. Yeah, it's actually, that's true, Justin. I feel better now.

There you go. No, no, no, no, no, no. He's like, he's one of the, one of the leading researchers on ketogenic diets, and he's also, he's the most out there, because there's a lot of people right now that are really doing some awesome researcher on ketogenic diets and ketones and exogenous ketones.

He talks a lot about exogenous ketones, which are basically ketone supplements you can take that will increase ketosis in the body and there are effects on everything from neurodegenerative disorders to cancer, research on Navy SEALs. He talks a little bit about that in the episode. I was so excited. I'm most excited about this is, you know, we talked about the keto genoc diet, you know, about six months ago when my pump went keto. And, you know, even us, we are not like the leading researchers on the ketogen. We're not even like, we're not even telling everybody to do it. And, but what people what you're, what people, most people are going to get in the next year to years to come with the keep because so much science is coming out is all the way the,

the industry is going to try and make a buck off of it. Yeah. And one, I'm so, why I'm so excited to bring this to everybody is you get to hear a, a, the man, the man when it comes to, uh, the study and research that has gone into the ketogenic diet. And from a non-bias point, not someone trying to sell you a book or try and sell you, listen to what I have to say, pure research, pure science, what we know for sure, what we're still learning. I just, and even when there's a point in this interview

where Sal challenges him and kind of asks his thinking on it and did listen to the way he responded, it was just like so beautiful I'm like love hearing someone trying to sell it sell you on it. Exactly not trying to sell you on the idea at all He's just trying very objective. He's very objective. He's presenting information This is what I like about Talking to scientists a lot of times is that if you get the right ones who are just really passionate about the work You don't feel like they're biased, even by their own work.

They try to remain objective, which he does a very good job. Not to mention the guy strong as hell too, and he works out with a lot of really strong guys. So he kind of, he understands us on another level. He's like us, but like way smarter. And stronger. And stronger. And stronger.

And stronger. And some apparently too. Damn Damn ruined. That's horrible. You know, we did a good job, I think, of trying to ask, I mean, God, I could have spent three hours straight of just question after question after question that I had for him and hopefully we'll have him on as a guest again sometime. But we had some good stuff that's related to building muscle, to burning fat, to performance, to cancer, how this is, to diabetes.

We covered some really cool things. We even talked about how bolking, how you can bulk or gain muscle on a ketogenic diet, because we've had a lot of questions about the pros and cons of that, for sure. Without any further ado, you're going to hear us talk to Dom Diagostino, he's the associate professor at the Department of Molecular Pharmacology and Physiology in South Florida, University of South Florida, excuse me. He's also a scientist at the Institute for Human Machine and Machine Cognition.

You can check his podcast, at least on a podcast called Metabolic Optimization Podcast. It's relatively new. A couple of sites you wanted to plug, ketonutrition.org and metabolic optimization.com. So here you go. Check us out. So I guess we can kind of get into it a little bit. Yeah, let's do that. I'm going to have a little kid Christmas right now. Well, we'd ask you questions. So, Dom, I first, I'll tell you how I first heard about you. Now I was familiar with ketogenic dieting

before I knew who you were and this is because I have a very close family member who has epilepsy and so that's how I got introduced to ketogenic dieting and how it could potentially help. Luckily my family member responded well to low dose medication. They didn't have to do this but I knew of ketogenic, you know, the effects of ketogenic diets on things like seizures because of that. And then I heard about you because you did something very interesting that blew me away.

You did it fast for seven days and then you did, you did lifted 500 pounds, 10 times and did a single with 585 or something like that, is that correct? Yeah, that's awesome. Yeah, that's so that's pretty crazy I know that's what we we actually we wrote a guide about fasting also about a year ago So one of our books is actually all about fasting so we're also huge fans. Yeah, you'll start to put together Why we're we're a big fan, you know a lot of things that you you talk and discuss We we're trying to share and spread a lot of that good war too. So how did you do that?

Was that an experiment, self-experiment that you did, where you fasted for seven days and then went into the deadlift? Yeah, you know, I've been kind of training for a while, just recreational lifting and stuff, but I got into, you know, just going back, the research that we do now is developing ketone supplements and really harnessing the power of nutritional ketosis. you know, just going back, the research that we do now is developing ketone supplements, and really harnessing the power of nutritional ketosis. And I was inspired by work that was done by George K. Hill back in the mid-60s at Harvard Medical School of all places, actually.

And this is before IRBs wouldn't let anything approve. They did a study where they fasted individuals for 40 days. And they looked at the AV difference, like the blood going to the brain and from the brain, and away from the brain, and looked at the metabolic substrate utilization, and showed that the brain shifted from using glucose to using ketone bodies.

And I studied sort of all the metabolic parameters and even talked to people that were involved in that study. The main George K. Hill actually passed away a few years, but I did get to talk to them before. So that kind of inspired me to do a seven day fast and to do all my blood work and also to see how I, you know, what my performance was like, you know, at the end of that. So actually, I had to give a couple

lectures. I was speaking, you guys are in fitness field, I was actually spoke at Lane Norton's fitness camp on the last day. And so, and we went to Powerhouse gym, which is, you know, gym where I train a bunch of guys train and just testing my strength, you know, and it's not, it wasn't like the PR by any means, but I realized that it didn't really tap into my low gear strength, which I thought, I kind of had a hunch it wouldn't really, but it didn't really impact me as much as you'd think after.

And I lost about, forget if it was seven or nine pounds throughout the one week of fasting. So you found that your strength, your maximal strength didn't really get affected from fasting for seven days. What are you talking about, telling the markers you notice? It's kind of, yeah, my, like my peak strength, and I'm kind of at my, my best I would guess, and I'm hitting the general law. I could do 585 or 10 or 12 is my best, but I can usually, and like 675,

how tall are you? Four, five. I'm a little, a little bit over six foot. Okay. That sucks for you. Didn't, you know, and I didn't want to go crazy, too crazy and like pull something and and I was feeling at six and seven days, even though I was drinking a lot of water and getting in minerals, I was getting a little bit like orthostatic hypertension, you know when you're sitting and you stand up, like your blood pressure was just really low.

Sure. And my heart rate was like, I think in the 40s, so it was like, you know, I was starting to feel it a little bit, so I didn't have a whole lot of energy reserves left. So I was just starting to feel it, but I was functioning at a level beyond what I thought I would be able to, you know, prior to doing the fast. And it was really pretty much a water only fast with some minerals. And I'm kind of interested in doing the seven day fast again, but with ketone supplementation.

So I just haven't, I wanna be sure I have the right block of time where I can, you know, do all the measurements and the blood work and do kind of a variety of things to assess my fast. Well, Dom, how did you start your research into ketones and the effects of the brain or, you know, ketogenic diets in particular? Would drove you to study that? Was it something you were directed to do? Was it something you had a passion for?

Yeah, 10 years ago, a little over 10 years ago, as a post-doctoral fellow, I did my PhD looking at the effects of low oxygen, which would be hypoxia, and then when I graduated and did my post-doctoral fellowship, years ago is looking at hyperoxia. So the military, specifically the Office of Navy Research, wanted to determine what was the cellular and molecular mechanism of CNS oxygen toxicity seizures that Navy seals and special operations diverges will get if they use a closed circuit rebreathing device, which is a small sort of rebreather that goes on the chest that allows you to dive underwater, and there's a stealth component, so there's no bubbles that come up when you're diving underwater,

like open circuits. And the benefit is that it's very quiet. You have a decompression sickness, nitrogen, narcosis, those things. But if you go down to just 50 feet of sea water, you could have a seizure in like 15 minutes. And this is because too high of oxygen concentration. Yeah, oxygen is stimulant, you know, at certain levels., oxygen is a good thing, obviously, but too much of it can overwhelm your brain's antioxidant capacity.

And it also functions, as I mentioned, like a stimulant. So you get essentially an over stimulation of the brain when the oxygen concentration gets too high. And as you go down in depth, the concentration of the gas that you're breathing, which would re-breather be pure oxygen, increases proportionally. So, you know, at, at a hundred and 34 feet of sea water, that's five atmospheres.

So if you're breathing, like we're breathing 20% oxygen, right? So on a re-brither, you're breathing 100% oxygen. And then if you go down to five atmospheres of sea water, which is like 132 feet, that's, you're breathing like 500 times in the amount of oxygen. And so that causes seizures in these very high-trained soldiers. And you found that eating a ketogenic diet or having them run off of ketones help prevent that?

Yeah, so the military has been looking at anti-seger strategies for a long time. And anti-convulsant drugs are kind of the things that they would go to. And I became, you know, I'm in a pharmacology department, so I was mostly interested in drug therapy to prevent this from happening, but then I had a guy that I was communicating with by the name of Mike Dancer, and he was kind of a fitness guy and a competitive bodybuilder, and he was getting, he had temporal lobe epilepsy. And I started doing some research to help him, and I found out that ketogen, NICDIA had a very interesting history, that it was actually a medical, you know, a metabolic-based therapy for drug-resistant or drug-refractory epilepsy. And it's origins date back until like the 1920s and 30s. And it was kind of based upon the idea that, you know, if you get your metabolic physiology

in like a fasted state where your blood glucose is low and your ketones are elevated, that produces a pretty profound anti-seizure effect. And the ketogenic diet can mimic the metabolic state of fasting. And I thought that was really interesting. And I came across the movie by Merrill Streep that many people probably don't realize she did a movie on the ketogenic diet

which is the first to do no harm. I did, I did. And she did the movie for Jim Abrams, movie on the ketogenic diet, which is the first due to no harm. And she did the movie for Jim Abrams, the Hollywood producer, who had a foundation called the Charlie Foundation. So I came across this movie and then I actually went to PubMed and I pulled a bunch of references out. And I realized that the data, the research was overwhelming showing that this was a highly

effective strategy to prevent seizures. Even when drugs failed, the diet worked like two thirds of the time, even when all the drugs failed. So I was thinking, wow, it's grossly underutilized. It should be like a frontline approach, really. But it just wasn't getting much attention. And so I contacted my program officer and I said, maybe we can develop a nutritional ketosis strategy

to mitigate oxygen toxicity seizures. And he kind of appealed to him, but he didn't like the idea of a carbohydrate restricted, high fat diet for like a warfighter, a Navy SEAL. And then I dug up a little bit more some information hydrate restricted, high fat diet for like a warfighter, an ABCL. And then I dug up a little bit more some information and I saw that DARPA had funded the development of ketone esters for warfighter performance like years ago. And the research was ongoing.

And I realized, wow, what if these ketone esters at mimic the state of nutritional ketosis could mitigate oxygen toxicity? It's putting your body into nutritional ketosis, like the diet, right? So you have something that could prevent the seizures and also enhance warfighter physical and cognitive performance, which was another sort of more or less top secret study that DARPA was running. So I was able to acquire a number of ketone esters, and we tested a variety of esters and found the compounds that were most efficacious at preventing oxygen toxicity seizure in our rodent model. So they are the ones, and we since developed

other forms of ketone supplementation, and that really kind of was the start of it. And that was about 10 years ago. But even prior to that, I was developing various technologies. My post-doctoral project was developing an atomic force microscope inside a hyperbère chamber. So we could look at the level of the membrane and the mitochondria and just cell activity, what was going on, you know, simulating a Navy SEAL dive, what was going on at the level of the mitochondria, you know, what was going on as far as free radical production in

the cell. So a lot of these cell-based in vitro studies that were giving me clues that if we just targeted cellular metabolism, then the cell could preserve its bioenergetics state and it's prevent its hyper excitability in the context of a big oxidative hit, like hyperbaric oxygen, it's 3, 4, five atmospheres. Well, there's a lot of studies on, you know, ketones and their neuroprotective effects and how it protects the brain. And I've heard scientists even refer to ketosis as a prefer, as the better, or, you know, we evolved to utilize glucose and glycogen and we probably started off using ketones because it seems to be a more efficient way of using energy for the cells.

Is there any accuracy to that? Yeah, you know there's a lot of work done by Christopher Boe and John Rowe who's at Barrow Neurological Institute. He now runs the pediatric epilepsy up in Calgary, Canada, and Eric Kosoff, and all these guys, I connected with all of them. I would probably annoyed them because I was constantly just calling people asking them questions. So this idea, then, in the medical community, even the medical students here, I have to teach them that ketones are not metabolic poison.

In the context of type 1 diabetes, where you have an absence of insulin, you could have runaway ketogenesis. You have ketosidosis. Yeah, ketosidosis. So, you have, in that scenario, you have very high concentrations of glucose, usually. And then runaway ketogenesis, you know, there are livers just pumping out massive amounts of ketones, and it can produce a situation that, you know, could be very deadly. Excluding type one diabetes, actually, I have a student who's, you know, a big lifter

of the guys like, you know, 6'4", 250 pounds, and he's on a ketogenic diet, basically, to manage his type 1 diabetes. So even though type 1 diabetes has that stigma, the ketoacidosis stigma, if it's well-controlled and you have a good handle on your insulin, someone could follow a ketogenic diet and reduce their insulin requirements and manage their glycemia much more effectively. So that's kind of like another story. But if we get to the original question in your asking is does the brain prefer ketones over glucose? And that's a question I get a lot. And I think the answer is that the brain will use whatever's

available, right? And in some cases, it will prefer to use ketones over glucose, for example, in an aged phenotype. So as we age, the brain's ability to use glucose as an energy source decreases over time. So you have decreased activity of enzymes like pyruvate dehydrogenase complex or internalization of the glucose transporter in the membrane. So if you look at the membrane, there's less glucose transporters at the level of the membrane.

As we age, we have vascular issues, so there's less brain blood flow. In the context of traumatic brain injury and Alzheimer's disease, the ketones function as an alternative energy source and would be, for sure, a preferred fuel source over glucose. In that, and preferred, but my definition is that you would derive more energy for ketone metabolism than you would with glucose metabolism. But in the context of a normal healthy person, I just look at it as kind of an alternative fuel that's available, and the brain will use kind of whatever's available. One could argue that if the same thing applies to the brain as does for the heart,

it's been demonstrated in a number of elegant studies that the hydraulic efficiency of the heart is enhanced with ketone metabolism, versus glucose metabolism, meaning that you essentially derive more ATP per oxygen molecule when you metabolize ketones for energy than you do with glucose. And- Well, it seems interesting.

It's interesting to me because I've heard of Alzheimer's as being referred to as type three diabetes. I just breathed out that. Yeah, yeah, yeah. What is the validity behind that?? I've heard that thrown around a little bit. I've even used that myself because I've read some research stating that it really has to do with the brain's inability to utilize glucose. That's why they're calling it that type three diabetes. The lead investigator that's looking at this, and he does a glucose PET scan and a ketone

PET scan. And he does like a comparison of the two, and that would be Stephen Cunein, he's in Canada. And he presented at our Metalbox Therapeutics Conference. And he showed that as we age, our ability to use ketones for fuel does not decrease. Whereas with glucose, you get a plateau and a decrease in brain glucose utilization as we age. So there's a compensatory effect of ketones kind of filling the gap to help restore brain energy metabolism

that's associated with impaired glucose metabolism as we age. So yeah, there's a good rationale for using ketones as an energy source. And I believe it doesn't necessarily apply to the aged phenotype or those with mild cognitive impairment or even advanced Alzheimer's disease. I think there's benefits that the normal healthy person can get to. A lot of the work, it needs to be appreciated that a lot of this work looking at ketones is sort of on a disease phenotype, if you will. There's not a whole lot of data on normal healthy people.

So that's kind of the question that I get. Well, yeah, it works in this disease. So that disease, and it helps restore mitochondrial function, mitochondrial energy production, but we'll have benefits to a normal healthy person. And I think that's, yes, especially under stress conditions. So that's kind of answer to my question. I was going to ask because of the difference

between like a medical versus like just a nutritional between the two, like the difference between the two of those, the description. Yeah, yeah. So a lot of the work has been done with ketogenic diets and we extrapolate that work to just exogenous ketones, too, is something that we're researching. But there's emerging applications for the ketogenic diet, and we realize now that it's managing drug-resistant seizures because it's

enhancing brain energy metabolism. And it does it independent of the etiology, which means you could have, you know, drive a syndrome, you could have like temporal lobe epilepsy, you could have glucose, transporter, type 1 deficiency syndrome, angelic syndrome, and all these cases, the ketogenic diet is a remarkable tool

for pretty much curing seizures in those disorders. There's a big mystery behind the mechanism of the ketogenic diet, and it's just not just one mechanism. It's many sort of mechanisms working in synergy from enhanced cellular bioenergetics, reduced frost, reactive oxygen species production. There's an increase in the GABA to glutamate ratio, which excess glutamate is excitotoxic and can cause seizures. And in elevation of GABA or GABA Urgeic activity in the brain can help dampen some of those seizures.

So, there's elevated adenosine, there's elevated carnaseine and answering, we're finding in our metabolomic studies. So, there's many different mechanisms kind of working in synergy, and I think that's unlike any other drug out there. And we know the ketogenic diet works when a whole pharmacopia of different drugs fails. So it's probably working through a mechanism that's independent of any drug that's out there. Interesting.

And, like, totally speaking, I've always consumed a diet that was relatively low in carbohydrates because I felt better, but I didn't do a full ketogenic diet, you know, with a very high fat intake and I even dropped my protein intake until about maybe about six or seven months ago. And one of the, one of the effects that I noticed right away was my reduction in, in just systemic inflammation. Like I ate a healthy diet before and I went into ketogenic, and I still ate healthy, you know, whole natural foods and balance, but I noticed a dramatic reduction in inflammation,

and that's one of the number one comments I get from people who go ketogenic, because they notice that they have less inflammation in their joints and they feel less stiff. What could be the mechanism behind that? Are ketones or is it ketogenic diet, in fact, anti-inflammatory? Yeah, that's a good question. We published a paper on this with our colleagues at Yale University. I guess just to give you a little backstory, Professor Dixit, whose name is Deep Dixit, he's at Yale University and did a lot of

kind of innovative research on calorie restriction, you know, and various mechanisms of type two diabetes and inflammation related to type two diabetes. And he reached out to me and said, type 2 diabetes and he reached out to me and said, you know, could you develop a diet that elevates beta hydroxybutyrate? Because he thought a lot of, you know, calorie restriction works remarkably well in many animal models and in humans for like, you know, correcting type 2 diabetes and many other disorders. And it has a remarkable effect at reducing inflammation. So he was, he was under the opinion that beta hydroxybutyrie was one of the metabolites that was working to suppress inflammation. So we developed a diet that we kind of formulated here at University of South Florida and we sent it to Yale University

and it was conducted by his team of researchers up there, probably about 15 different people. And it demonstrated that the ketone metabolite beta hydroxybutyrate blocks the NLRP3 and flamizome mediated inflammation. So this particular inflamizome is kind of like a hub. And when it gets activated, it's, and when it gets activated, or when it's suppressed, it can attenuate type two diabetes, it can attenuate multiple MS Alzheimer's disease, age-related cognitive effects, GALT,

there's many different pathologies that are associated with the activation of this in flamazon. So if we can suppress it, that that would be very important. And that's exactly what his studies showed that it was, and it did it through a metabolic independent mechanism. So it did it through a fairly complicated mechanism. That was more or less independent

of the metabolic signals that we were sort of most familiar with, like AMP kinase and MTOR and things like that, or TCA cycle intermediates. And that was published in Nature Medicine, which is kind of the top tier, the gold standard of scientific research. that the top tier, the gold standard of scientific research. Well, Dom, we've been seeing a lot of information now on fasting and how beneficial it is for the body for longevity and for health. And I'm noticing that a lot of the effects of the ketogenic diet match what you'll get from fasting.

Do you think a lot of the benefits of fasting are coming from the fact that when you fast, your body tends to go ketogenic? Do you think that might be why fasting is so good? Or do you think the reverse that may be a ketogenic diet mimics some of the effects of fasting? And that's why it's healthy. Or why it's got some of these protective effects, I should say.

Yeah, so Dr. Longo has proved, you know, advanced that all the benefits of fasting. So even fasting before you have chemotherapy or fasting before radiation, can have tremendous benefits for cancer management too. So that was really the take home message of the manuscript that we presented. And when the news media kind of jumped on it, they basically said, you know, they found the metabolite that's contributing to all the benefits of fasting.

And it would be the ketone body, beta hydroxybutyrate. And I think there's good evidence for that, but I think there's a lot of other things going on. And I think that's the ketogenic diet mimics metabolically the state of fasting. If you have someone who's following a Stric ketogenic diet, one that's formulated, especially one that's formulated to manage epilepsy,

like a four to one or three to one ratio, ketogenic diet, and you looked at their blood, it would look like they had fasted for half a week or more because glucose would be low, their ketone body is elevated, obviously, and the hormone insulin would be suppressed. And it's a suppression of the hormone insulin that drives hepatic ketogenesis, and that's really the telltale sign of someone who's fasteded and that persistently stays that's a constant feature of the ketogenic diet. So that being said, Dom, what's your take on someone who's trying to actually build or gain

muscle on a ketogenic diet because it does suppress things like insulin. We know that's important. Have you experimented much with this at all? Well, yeah, I think the approach would be, you know, you got to figure out what your goals are, right? So, if you're 18-aged, and you're trying to gain weight, and for football or whatever, so even a ketogenic diet or even a low carb diet is probably not ideal. When you're young, and you guys could probably relate to this, you know, when I was in

the teens and early 20s, I can eat at the time. I was eating massive amounts of carbs, 500, 600 grams of carbs a day and doing just fine. Trying to gain weight. But in the context of someone trying to gain size and strength on a ketogenic diet, we know insulin, not only is it anabolic, but it's also very anti-catabolic.

And the effects may actually be due, you know, as far as lifting, we could probably exploit it best if we kind of think of it as an anti-catabolic hormone. So a little bit of calories in the form of a little bit of carbohydrates maybe and especially some branch chain amino acids and protein right before we work out. So you know for someone my size like a hundred kilograms or so I would probably only want to max out at 150 grams of protein per day but I would try to bolus that in and around my workout. So, right before going in and after to mitigate some of the catabulk effects of working out. And of course, to fuel growth, you need certain amount of calories.

But a lot of it comes down to just calorie count. If your calorie restricted, obviously it's going to be very difficult to gain size and strength in a calorie restricted state. I think it can be done with the right training, but when it comes to putting on size and strength, you really have to adjust the calories to maintenance level and a little bit over with a ketogenic diet. I was just going to ask you that because I also, and I don't hear, you know, when I went through the ketogenic diet, I, a real similar effect like Sal had, but then I switched over

to, okay, I'm going to, I'm going to try and bulk on this diet. I'm going to try and add size and, and see if I could do it. I was enjoying it so much. I love it for, for maintaining health and balance or I could do it. I was enjoying it so much. I love it for maintaining health and balance or even to lean out. I thought, okay, let's try to add size and weight while on it. And I actually found it really challenging. And I think mostly just the fats just satiating me.

I mean, and I also felt like I could get away with more calories on the ketogenic diet than I could on a more balanced diet. So I found like the surplus that I needed had to be even more than what I would normally have to surplus if I was running or taking in carbohydrates on a regular basis. Yeah, that could be it.

I don't know if there's any kind of metal block advantage that they say with a ketogenic diet over a carbohydrate based diet, I kind of doubt that's it. I know there's some people out there that are trying to advance that sort of idea, hypothesis. But the appetite suppression effect is very real though. And that probably comes from just maintaining your blood glucose levels within a certain type parameter. So when you eat, when you bowl this carbohydrates, like many fitness guys do, maybe every three hours, you're eating like 50 grams of carbs or something,

you have that post-prandial hypoglycemia. You eat the carbs, you get the release of insulin, and your blood glucose comes down, and after two hours later, it takes a dip, and that little dip can cause some hunger cravings, and it probably calls you to go seek out more carbohydrates to eat again. So that's pretty much abolished

or significantly attenuated if you're on a ketogenic diet. Yeah, because you just don't have the makesets. And yeah, and I think from a military perspective to if you're able to maintain sort of the appetite suppression can help to preserve your cognitive and physical performance over time. So there's less impairments or deficits in cognitive function if you're resistant against hypoglycemia.

Right? So if you get hungry, you're not going to really be experiencing your body. It's not going to be tongue. It's hungry because you don't get that hypoglycemic dip. So these are, these are reasons why the military is kind of interested in the digital genome, traditional ketosis too. What's your thoughts, Tom, on, you know, along those lines too of somebody who's, like, let's say, come in and out of it. So I then once again, this is anecdotal for myself.

I was curious if there's science behind it. I felt like, so I was a guy who's, I compete bodybuilding and I consume, I was consuming 400 to 500 grams of carbohydrates on a regular day. When I went ketogenic and then when I came back out of it, my body felt like it was like super sensitive carbs and I couldn't have more than 200 or something grams of carbs without feeling like it was like super sensitive carbs. And I couldn't have more than 200 or something

grams of carbs without feeling like I was just super bloated and overconsuming. Is there any science to that too that now my carbohydrate intake, it feels like my body doesn't even want that many carbs anymore? Yeah, you're probably just secreting more insulin in response to the carbohydrates and probably transporting it more efficiently. Also your...

That's good to know. A lot of it has to do with your kind of re-meaning and angiotensin pathway associated with your fluid balance. So, when people eat carbohydrates, they will release the hormone insulin and insulin can not only store carbohydrates and so are fat too, but it also causes a profound effect at retaining sodium. So when you go on a ketogenic diet, your insulin is suppressed. So you have, it has like a naturaletic effect.

So you actually excrete a lot of sodium. But when you get back into eating carbohydrates again, a lot of that initial weight gain is fluid. And it's an insulin and do sodium retention. It's not just all carbohydrates. It's like your body is just retaining more sodium and excreting less. So, and I've seen that happen, you know, I've seen guys gain up to like 30 or 40 pounds within a week. And that's not exaggeration. If they just go completely off their diet,

you could do a lot of damage. People don't realize, well, that, that, you know, just eating crazy for a couple of days is not going to do a lot of damage, but after contest dieting, you are superbly set up to store fat extremely efficiently. So you're basically jamming a lot of fat into your adipose when you kind of completely go off the diet. It's funny you bring that you start feeding like that. You bring that up. That's a part of what brought the three of us, gentlemen together in the show was, you

know, because I've got this experience in the bodybuilding world, I was just blown away by how many awful habits that are out there. And these are the individuals that represent, you know, the covers of magazines and what all these people are looking up to and seeking for advice. And I thought, oh my God, the way that we do things is this extreme crash dieting to these binging after a show. Like, I'm like, yeah, this is just this so unhealthy. So healthy. This is what these are the people that represent, you know, our fitness industry. And man, that's the problem with that I have big time.

Well, what's interesting to me, Dom, is you just talked about the fluid, or the sodium retention, you get, you get, you get from eating, you know for meeting carbohydrates, lots of carbohydrates. When I hear bodybuilders and physique competitors and guys in the gym who say, oh, I'm low carb, my muscles are flat, I need to refill my glycogen. Now many carbs and they're going to fill out. I used to believe that and then I saw a recent study, and I don't remember who it was done by, or within the study they showed that keto adapted athletes actually had

as much glycogen storage in their muscles as other athletes who ate lots of carbohydrates. So now hearing what you're saying, I bet you what they're feeling, the filling out process is probably just from the sodium and the water. Absolutely, yeah. Right?

Oh, yeah, yeah, yeah, totally. So yeah, I think the article you're referring to would be the article in metabolism and the first author would be Jeff Bollick, who's a good friend and colleague of mine. And senior author would be Stephen Finney. And they looked at guys that were extreme athletes that had super high output and they had guys that were carb adapted like completely almost fueled off carbs and guys that were keto adapted pretty much fueled off fat and when they looked at muscle glycogen not liver but muscle glycogen they saw that the glycogen stores were topped off and

guys that were fat adapted because being fat and keto adapted is incredibly glycogen stores were topped off, and guys that were fat adapted, because being fat and keto adapted is incredibly glycogen-sparing, because you shifted your metabolism to using fats for fuel. So you're going to sort of preserve that the muscle is going to preserve its glycogen content pretty effectively. And that has made your practical benefits too, because if you have two guys at

the start of a race and say it's like an ultra endurance event, and they have to run a hundred miles, you know, and sometimes these guys run in the mountains and everything is pretty crazy. And you have a guy that's fat adapted and a guy that's carb adapted, and they both have the same amount of muscle glycogen and they start running. The guy that's carb adapted is going to need a tremendous amount of carb refeed during the actual event compared to the guy that's fat adapted because we have essentially an unlimited amount of fat.

Even a lean person has like 40 or 50,000 calories of fat. So they'll have more than enough fat. But, you know, a carb adapted person is going to tank out at what you have about, you know, maybe at the most, like 2,000 calories of carbs total. And if that gets depleted in these ultra endurance events, they're gonna tank. Well, interesting, because two things, number one, speculating how humans live for most of our time on Earth, we probably went long periods of time without food. And so it only makes sense that that would be, where we could survive the longest running on that type

of energy, most advantageous. And the second thing that I was going to comment on, if you look at all sports, one particular type of sport or types of sports that have really started to grasp on to ketogenic dieting seems to be the ultra endurance at ultra endurance athletes. They seem to be the ones that are really jumping on the ketogenic diets more than other athletes like let's say football players.

Yeah. Now is this because is this because a ketogenic diet is fantastic for that long, long, long types of endurance like you're saying and is it also because if you're doing other sports that require lots of speed in power, you're probably better off not going ketogenic. other sports that require lots of speed in power, you're probably better off not going ketogenic. Yeah, well, that, that's a good question. You know, they are the athletes that sort of represent, they're kind of like a good study of fuel utilization. So, most of the research, you know, has been done on them and not a whole lot of research,

published research has been done on them and not a whole lot of research, published research has been done on strength athletes. So that's what we hope to do and plan to do. We did get a publication accepted last week in general of strength and conditioning. And I think there's an embargo on it. I'm not sure I can even talk about it yet. So I gotta look on PubMed. I forgot. So So that sort of

answers. So we look at body composition, hormones, and strength, and athletes that fall a Western diet or a ketogenic diet. And essentially, it showed that the ketogenic diet you could add strength and muscle on a ketogenic diet that was well formulated more in line with a modified Actin's diet. So you had about 20 to 25% of it protein and not the restrictive protein of the medical ketogenic diet. But the big thing is that there was greater fat loss, you know, with the ketogenic diet. And even when the calories were sort of matched, like you had a U-Coloric, isocloric, sort of calories between the two diets.

Interesting. Well, this kind of puts the whole, one of the, another thing that puts the whole, a calorie is a calorie, you know, narrative that we've learned in nutrition. It seems like more and more research is proving that they're not necessarily all the same. Well, I think we need to appreciate that the calories that we eat have, you know, the food is chemical energy, right? I mean, it has a chemical, like, almost a drug-like effect on our physiology.

And I think we need to appreciate that. That if we carbohydrates from broccoli versus carbohydrates from a pop tart, it's going to have a different hormonal effect on our body. I think that's pretty easy for most people to realize. And I think in the context of strength athletes, as long as the workouts are within an hour, unless you're doing super marathon workouts, then you might be walking around with depleted muscle glycogen. But the body has a pretty good ability to compensate and restore muscle glycogen as long as you're not calorie deficient.

If you're calorie restricted, then of course, your muscle glycogen is gonna take a hit, especially if you are really going at it in the gym. But if your calorie level meets your energy needs, your body will find a way to ensure that your muscle glycogen is restored, to a certain extent, for sure. I see.

It's under the line. It's the need of you at through that lens, through the calorie, the calorie lens, because a lot of people throw that out the window. You need to appreciate that when you go on a ketogenic diet, you may inadvertently calorie restrict. So if you start following the diet, you may experience, you know, flat muscles initially because your your body is an adapted to recenthizing muscle glycogen in the absence of carbohydrates, but it will adapt over the the period of a couple weeks. Exactly. And we're not optimized until about three

months, but it'll happen. Exactly. It will. It also, like I was, you know, I was an athlete for a long time and all we've heard about is, you know, how we need to load up on carbs, you know, for an energy source.

And from, you know, you explaining being fat adaptive, you know, versus not, you know, from what it makes, you know, sense to me as far as, as far as not just the marathon runner might benefit from this, as long as you're fat adaptive, a football player, a basketball player, somebody like that might also benefit from this. Is that... Well, without sounding too much of a commercial for Kid of Genic, I wanted to switch gears

a little bit, and I want to know if there's any negatives. I've heard of potential hormonal effects of long-term ketogenic dieting on thyroid hormone. And somebody made an interesting case to me about a week ago where they said, well, eating a ketogenic diet does simulate a low or subcalorie, you know, subcalories in the body are like fasting and it could be a stress on the body, could being on this long-term cause any negative changes or effects in the body that we may want to come out every once in a while. Yeah, to say no, to make a blanket statement like that would probably not be a good idea because we're all a unique metabolic entity, I like to say, because we have some genetic factors in us. Some may have a higher

rate of synthesis of various fat oxidation, beta oxidation enzymes in our liver. So we make more ketones than other people. And I think it's the more data that I look at, even in like an in-bred strain of rat, we see variability. So I think the variability is going to be much higher in people, especially if their geological ancestors are from a very northern climate versus Mediterranean or versus an equatorial climate. So and that may account for some of the things that I've observed with people of a few people, let's say about 20% of the people who try a ketogenic diet, it just kind of doesn't work for them. And I thought maybe they weren't formulating it well,

maybe they just, you know, they weren't strict enough, they were getting in excess carbs. And when I say it doesn't work well, that your body is a pretty good indicator of, you know, kind of what's happening. And if you don't feel well on a ketogenic diet after months of trying it, where you give it your best shot, it's probably not the best diet for you.

But I, but I, that's not to say that a low carb wouldn't be good. But a ketogenic diet is a pretty extreme version of a diet, uh, if you're not used to following it. Well, I'm happy you said that because, um, you that because you're right along the lines of what we tell people when we talk about different ways to eat because just being trainers as long as we have been, I've noticed such huge individual variances and everything from workouts and nutrition. So, yeah. Absolutely.

So you guys, I'm sure, seeing it. There's some people, even you'll see their LDLP like skyrocket and sometimes even their triglycerides go up and their c-reactive protein will go up to. And these are completely opposite of what the majority of population would experience if they did a ketogenic diet. Now, one might be able to argue that maybe the macro nutrient sources you know, sources that they chose, maybe if it was a, like a really high dairy-based ketogenic diet, was contributing to that. And I've seen some people follow ketogenic diet and, you know, remove the heavy cream and just sort of add more fish oil or fish and avocado instead of you know

lots of you know hamburger and dairy and they do much better like their numbers improve. So there's you know there's a discussion there that you can kind of get into versus you know limiting dairy limiting the ratio of polyunsaturated, Versam, versus saturated fat in the diet. And I have some opinions there, and I like to kind of put a lot of time and thought into formulating what an ideal diet would be. Interesting.

But I've seen people just not respond. They shift their diet all around. They just don't respond to the Cajunic diet. So it's really up to the person to monitor, to do some self-monitoring and blood work. That makes me really interested in how you eat. I'm curious if you're like us, the three of us, you know, being nerdy fitness guys, I don't know if I'm, and people always ask us, what do you guys do for diet or how do you guys eat every day?

I'm like, man, it's such a tough answer for me because I'm constantly experimenting with my body and trying different things. And when I went keto, I actually, it changed my whole relationship with fats in general because we've been, even as trainers, you know, we've been so scared to run that high of a diet, a high of fat diet and all the positive things I experienced with it changed the whole relationship that I had now with fat and carbohydrates. And now I probably run closer to 100 grams to 150 grams of carbs.

That's it now and a much higher fat diet because of my experience with ketogenic. Now are you somebody who sticks to the same way of eating or are you constantly doing the same? Are you manipulating a lot? Yeah, I do stand some form of nutritional ketosis pretty much all the time. And I think a lot of it has to do just because that's my area of research. So I'm always experimenting. So even if my diet doesn't reflect on paper as far as macronutrient profile, that of a ketogenic diet, like I'll be taking some form of supplementation that will kind of put me into ketosis. But my diet's, you know, it's definitely low carb,

almost always, and typically always ketogenic or modified ketogenic diet, I would say, which would be about 60 to 75% fat and the balance being protein with my carbohydrates coming primarily from things like salads, green vegetables, cauliflower, nuts, avocado, a little bit of berries and dark chocolate. I might have it at nighttime, but other than that, like this morning, I did at breakfast this morning and I had some eggs and some trout and a little bit of salad from the leftover night before. That's pretty, I varied up a lot, I varied the types of foods and I think that's important

just for a nutrient profile. But I eat pretty much the same way all the time. Lots of eggs and fish and green vegetables, I probably described as my diet. Now, Dom, I read an article the other day that referred to cancer as being a metabolic disease. And I know you've talked about this as well in relationship to some of the studies done on ketones and ketogenic diets and how cancer cells basically don't have the ability to switch to using ketones. They just use glucose and when you're on a ketogenic diet,

it seems to have some favorable effects on cancer. What does the research look like now? Yeah, I don't know, yeah, be curious what article that was, The New York Times actually did an article on this and sort of reviving this idea of what's called the Warburg effect. And the Warburg effect is a phenomenon in cancer that we've known, you know, since Otto Warburg. He got the Nobel Prize for his work in metabolism. There's no doubt in anybody's mind including all the mainstream cancer researchers, like guys like Craig Thompson and Lou Cantley and Michael Bishop. I mean, these are like the pioneers of cancer research. They are all like the pioneers of cancer research, they are all, will admit now, maybe it took a little bit of time, that cancer is a metabolic disease in the context of it has a metabolic phenotype, right? So we use a fluorodeoxyglucose PET scan to locate, to show the aggressiveness in the location of cancer in

the body. Like a whole body PET CT is used for that. And that's more or less the gold standard, to show that you have cancer and also indicates the aggressiveness of the cancer by the amount of fluorescence or the amount of the intensity of the signal coming from the PET scan, which is an indication of glucose uptake into the cells. It's an indication that the cancer cells are out competing a healthy tissue around it for the glucose. Where the debate lies is the origin of cancer.

Does cancer have a metabolic origin? So is it? We will... Cancer definitely has a very unique and different metabolic phenotype. It consumes massive amounts of glucose relative to normal healthy tissue. And oncologists have known that for years, but I think it's time now and many other investigators do that we exploit that metabolic characteristic by designing a diet or even drugs that limit glucose availability to glucose hungry cells, and also a diet and drugs that suppress the the hormones that drive cancer growth and proliferation. For example, insulin, you know, in pretty much most cancers, 80, probably 90% of cancers, the hormone

insulin drives growth and proliferation and probably metastasis. Insulin's pretty much linked with IGF-1 and M-TOR and AMP kinase and all these factors that are intimately associated with cancer growth and proliferation. The ketogenic diet really suppresses many of the main drivers of cancer growth and it does it across the board, and it's really targeting molecular signaling pathways that many pharmaceutical companies like Roche and Genentech and the big pharmaceutical companies are scrambling to develop drugs that target the same metabolic pathways that the ketogenic diet nicely targets sort of in synergy with many things together. So there's been a revival in the interest of the ketogenic diet for targeting metabolically

targeting cancer. Fantastic. What kind of research, if you're able, I don't know if you're able to talk about what kind of research you're working on now, where you see the future of, you know, the research in this field. Yeah. So our lab, we kind of have a multi-pronged approach. So we develop and test ketogenic diets, and that could be different formulations of the ketogenic diet to sort of a more clinical-based one, to one that's a little more liberal in protein, similar to the modified Actins diet. And we've shown that both of these sort of versions of the ketogenic diet are quite impressive at retuting cancer growth and also most importantly improving survival in our animal model of metastatic cancer.

So we combine the ketogenic diet with hyperbaric oxygen therapy in one of our studies, because high levels of oxygen can reverse tumor hypoxia because low levels of oxygen can kick on oncogenes and various signaling pathways that could cause further growth and spread of cancer, including things like hip-1 alpha and VEGF. It tends to knock those things down. Hyperberecoxygen does, and it works nicely when it's combined with the ketogenic diet. So that's another area that we're looking into, exploiting sort of the oxidative potential of high levels of oxygen. And we're also looking at various metabolic-based drugs, like dichloroacetate, also called

DCA, and metformin. You guys are probably familiar with metformin. So we have one of my students who's just focused on metformin and also DCA. We have studies looking at branch chain amino acids to mitigate cancer, kectia, to reduce the protein loss that's associated with metastatic, stage 4 metastatic disease is really associated with muscle wasting. So we're developing strategies to mitigate that. So it's kind of a tedious process because all these things need to be tested sort of as

a standalone first with a standard diet. And then we're at the point now where we're starting to combine some of these therapies. So we have synthetic ketones that we're using. And we showed that synthetic ketones, even're using, and we show that synthetic ketones, even by itself, can reduce cancer growth and actually prolong survival in our model, which is a really good model, we think. So now we're at the point where we're combining a ketogenic diet, plus ketone supplementation, plus hyperbaric oxygen, and we've published recently a paper on that. And now we're interested in taking that non-toxic approach,

and then adding some drugs that can further target cancer metabolism, like DCA and metformin, maybe three bromo pyruvate. So the idea we approach it, we kind of think of it as a press pulse theory. So, the press would be like the diet, right? Because it would put metabolic pressure on the existing cancer cells. And the pulse would be like hyperbaric oxygen therapy or like three-week cycles of these cancer-specific metabolic drugs, you know, that really target cancer metabolism.

You know, higher doses, they are long, prolonged periods of time. They could be toxic if used for, you know, months and months. But if you, you compromise cancer metabolism with a ketogenic diet and just stop the growth in spread and then pulse various drugs, low toxicity drugs, then that would be the best approach, especially when you compare it to what is being done now with cytotoxic chemotherapy and radiation, which really compromises the health and even the overall survival of the patients in many cases.

Well, fantastic, we hope. You found some of the... Yeah, I wanna ask Don one more question. I would be so mad at myself, I didn't ask you, and I have a mind like yours on the radio right now. And my childhood best friend of mine, he battles with REM sleep disorder, or what they call RBD.

Are you familiar with that at all, Don? RBD? Yeah, it's known as that, or REM sleep disorder. I know, okay, so he's not getting into to REM. Yeah. And he has like these vivid, vivid dreams that he acts out. And they say it's actually like I believe like 95 of the person of the people that have this end up getting Parkinson's.

And I didn't know if you, if you had any, any research or study it's around this. It's not super common. And you know, you're definitely someone that I'd like to ask about it if I ever had a chance. Yeah, do you think that the neuroprotective properties of a ketogenic diet would help prevent? That's right. That's where I'm heading.

Would help prevent him from getting Parkinson's? Yeah, I mean, all the indications, you know, all that data that I've seen in vitro and in vivo indicate that ketones are neuroprotective and they would prevent oxidative damage associated with Parkinson's disease. So we know that Parkinson's disease is a degeneration of neurons in the substantioneigra and that area of the brain is kind of selectively vulnerable to reactive oxygen species and do cell death that has a lot of monolamine oxidase and a lot of free iron that can drive something called the fentanyl reaction, and ketones sort of enhance mitochondrial electron flow and enhance energy in those areas

while lowering reactive oxygen species. And there's been a couple papers published on this, actually. So achieving and maintaining a state of nutritional ketosis would probably help with sleep. I found it helps with my sleep. And many people have emailed me. One person was completely had narcolepsy and was on Modena Phil or Provigil that basically stimulant drug for 10 years and was able to completely get off of it when they got on the ketogenic diet and has been sleeping perfectly fine now. So I think the ketogenic diet could work in two ways. I think it definitely helps improve some people's sleep and it could give you some insurance or protection against oxidative stress that could be contributing to this disorder.

Just something to think about. I did my PhD in a sleep lab, or along with a sleep lab, and I really haven't ran into that disorder much, so I assume it's pretty rare. It's very rare. I mean, it happens to be my childhood best friend has it. And it sucks being the fitness guy that I am that coming to me, I didn't have the answer for him right away. So I've been researching myself.

And I was really interested in the benefits of the ketogenic diet. And like, Sal started to say about the, you know, being a protectant. I thought, okay, well, this at least could help because everything I found, nothing linked directly to the RBD or the REM sleep disorder, there was stuff though that I found on Parkinson's and how it could be beneficial to that. And I thought, well, if 95% of the people that end up with this REM end up, or RBD, end up going into Parkinson's, I would think that there would be some sort of benefits

to that for at least helping you from that, right? So. Yeah, yeah. I'm actually reading about it now. Yeah, it's really fascinating. We did, so parallel to that, we were doing some research in our lab on restless leg syndrome.

And restless leg syndrome is associated with they think maybe degeneration of those neurons through increased reactive oxygen species. So there was some interest in metabolic approaches and also ways to decrease free iron levels. So, high levels of iron in certain brain regions can contribute to degeneration of neurons, especially neurons related to Parkinson's disease.

So, just maybe something to look into. But- Interesting. Well, I will, I'm gonna look into this and if I can dig anything up, I will send you some information in regards to ketosis and this. Oh, I would I would love that. I would love that. Well, Dom, thanks for talking to us. It's been a pleasure. Yeah, we thanks for having me and appreciate it. I would love to do this again with you for sure. I know we there's so much more we want to talk to you

but we don't we respect your time. We know you're a busy man. Love knowledge there for sure. Yep. Thanks again, Dom. Thanks for having me thanks guys thank you for listening to mind pump the goal is to build shape your body dramatically improve your health and energy and maximize your overall performance check out our discounted rgb super bundle at mind pump media dot com the rgb super bundle includes maps and a ballad, maps performance, and maps aesthetic.

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