 So, check this out. We have something available called 30 Days of Coaching and we give it for free and this is what it is. You go on our site, mindpumpmedia.com, you opt in and you get access to a bunch of different topics that we consider to be the most important when people are getting started in fitness and wellness. Everything from basic topics like proteins, fats, carbohydrates and calories to more complex topics like your metabolism to other topics that are included in wellness, things like meditation. And what we do is we send you episodes where we've talked about these things in detail and we timestamp them so you can listen to what we say about these particular topics in detail and plus we give you more information. It's all free and it's our way of giving back to the Mind Pump listeners and the way you get it is you go to mindpumpmedia.com and sign up and it costs nothing. So just recently we had an opportunity to hop on a show, Travis Marziani, great kid, man, and we had an opportunity to try out his performance nut butter and all of us absolutely loved it. This kid, it's really great to watch what he's doing and just his work ethic, the thought that he's put into putting this product out. It looks amazing. It tastes amazing. It's all natural. It's keto. It's vegan. It's macadamia, coconut, and cashew nut butter all together and it's phenomenal. And he's trying to launch this company. So one of the things about Mind Pump, we've kind of been this way since day one is we've turned down a lot of people that we could have done affiliations with to make money. And one of the things we all agreed on is that anything that we'd ever talk about would be stuff that we support. Even a company like this that can't pay us any money isn't huge, isn't going to be a major affiliate. He's trying to launch his Indiegogo right now and get this business up and running and we want to help support him. So if you guys want to help us out to help him, go to mindpumpbutter.com. You could check out his Indiegogo right now and try some of this stuff out. Even if you guys just try a simple sample, it helps him out and you'll see you'll love it because I know all of us love it. So and give us great feedback please afterwards because anything we can do to help support him and help him grow this business. If you want to pump your body and expand your mind, there's only one place to go. Mindpump with your hosts, Sal DeStefano, Adam Schaefer, and Justin Andrews. Holy shit, we're finally dropping the Dom D episode. Oh my god. So we know you guys, if you have been fasting waiting for this, you may be dead. I know we've had fans that have been waiting to hear the Dom D episode. We have been waiting for approval from NASA. Those motherfuckers over there. He's not lying. That's the truth. We recorded this episode a long time ago. Dom came to visit us. We recorded an awesome podcast with him. We talked about, of course, ketogenic nutrition. Well, we talked about super top secret shit that goes down with NASA. And that was the reason he right away said, listen boys, as much fun as we had all the great stuff that we revealed and talked about, you cannot release that episode until I get approval from NASA. We literally got the approval yesterday or dropping it. He's got NASA stamped. We are dropping it for you guys so you guys can now listen to it. You guys get insider information on what's going up on Mars before anybody else knows. This is pretty cool. And now Dom was selected as one of only four crew members for the NASA Extreme Environment Missions Operations Expedition. He's going to go to the bottom of the Atlantic Ocean for 10 days on June 18th, simulating a deep space mission with similar objectives for exploration on Mars. And I think this is about how to use ketones and all stuff. It's a great episode. You're going to love it. So here we are talking to Dr. Dom Di Agostino. You know, Dom, we're talking about business and things like that. You know, and you're a major research guy. So how do you look at what you're doing like business-wise, like the future of what you're doing? Do you even care about? Like, do you have any sort of monetary drive whatsoever? You just research like, where's your head at with that? Yeah, that's an interesting topic because we were discussing that walking here, actually, we realized that a lot of people are latching on to what we're doing, whether it be an idea or intellectual property, even that we're generating through and making a lot of money. And I would like to develop a model, which is kind of outside of convention from an academic academia perspective, but to develop a model where the public interest in what we're doing is generating revenue that can feed back into developing the science and the application of the things that we're doing, whether it be a specialized ketogenic diet, a supplement or a very comprehensive, you know, metabolic-based therapy for whether it be cancer, epilepsy or Navy seal application or NASA application or something like that. But to develop a business model, and I think it's going to take some thought and creativity and maybe innovation to do it, that instead of trying to beg the government, the NIH has always gotten like a 20% cut in their funding. And that's where I'm supposed to be getting, you know, money for my research, but to do it through other channels. And because you really need to keep reinventing yourself and be innovative if you're a researcher, an investigator that wants to fund a lab and pay salaries. And I think the challenge that you have with that is what you guys, I'm sure you guys are aware of is from the research side, from the science side, you follow these protocols. You have hypothesis, you test them, you know, there's peer-reviewed process. The market side doesn't have any of that. So you could come out and be like, hey, you know, it looks like maybe, you know, ketones might have, you know, points in the direction that might have a fat burning quality. But we're going to study further and we're going to look deeper into that. And the next thing you know, there's five supplement companies like Fat Burner with new ketones. Already making a shit ton of money off the research that you started. Well, that's the challenge is competing with that speed. That's, yeah, if they're, you know, making the claims, they need to point to the science. So that's, I mean, we're reaching out to the companies that are selling these products and saying, hey, if you are going to make these claims, you got to put your, you know, your pocketbook where your mouth is and start funding studies. There's a lot of neurological applications, potentially performance, anti-cancer, things like that from pre-clinical animal data and maybe, you know, some emerging human studies. But, I mean, I'm going to call companies out and say, you know, I'm worth kind of the people who started this and you're misrepresenting the technology and the supplements by doing that. I think a good way to do that would be to be really open with that rather than contacting them privately, having a site and saying, these are the following supplement companies are making erroneous claims in regards to ketones and then list them. Because that would be like, if I was a supplement company, that'd be the last place I'd want my company to be on. That sounds like a great page for mind pump media, I feel like. Yeah, well, if you don't do it, we'll do it. We might have to talk more into this after this podcast is over because I feel like that's what we're all about. Well, it's not like Xammon.com. They do a little bit of like vetting with that. I love Xammon.com, but they don't call specific companies out. Yeah, they don't get that aggressive. I mean, we have no problem getting that aggressive, but I can see that because now you're looking at fire with fire, you know what I mean? Because they're really crafty at maneuvering around and taking their time and then finally they get five letters from you and oh, no, it looks like we're going to court, fine, we're going to stop or we're going to change our wording a little bit. By that point now, millions of people have bought their shit. The message is out. We've sent a lot of cease and desist to various companies and I have actually called them out more to their lawyers or our university did and the model that I encouraged companies to do is to educate, to bring, to pay people like Rob Wolf and academics and scientists to actually speak to the distributors and the representatives who are marketing this technology and have that mandatory before they go out and do sales and the company would pay for that to happen. Because otherwise they could be shooting themselves in the foot if they go out there and make all these crazy claims without promoting the science, by science, I mean peer reviewed publications and there's quite a lot of it out there and it's going, if you look on PubMed, it's going up exponentially because there's so much interest right now in your field. But they need to understand what these supplements are and what they are not and by promoting what they are not that's kind of shooting themselves in the foot. Now, Dom, what are some of the crazy claims that you're seeing right now? You don't have to name companies or anything, but what are some of the things you're seeing that you're like, no, that's not accurate or we just don't know yet in regards to ketone science or ketogenic science? Well, just quite a few, but the scenario that happens is that you get one or two people that get this crazy response, they lose like 100 pounds and then they're promoting the ketone supplement for that and they just happen to be a distributor too. So this is the scenario, I do get a lot of emails from people who do not go public with their story from parents that have kids, for example, so the ketogenic diet, you guys probably know, the only clinical application for it is for seizure disorders and it works remarkably well for that even when drugs fail and in some cases it doesn't work or it doesn't give full seizure control and supplements should not be marketed for this yet, but when used in conjunction with a ketogenic diet, they can further augment the therapeutic efficacy of the ketogenic diet to the point where it is now controlling seizures for a lot of times for very specific metabolic disorders, but even for just general epilepsy, but you have that will come out, some kind of story or anecdotal report will come out and then companies will say, oh, look, it's the supplement, it's not the diet where it's usually the diet and the supplement combined. Yeah, like the parents are working with Johns Hopkins clinical dietitian to set up the diet and it's not quite working to where they want it and then they add a supplement, they kind of go outside of the realm of conventional medicine and then supplement companies will sometimes harp on that and say, look, the diet cures epilepsy or the ketone supplement cures epilepsy. So we know that's pretty established now that a ketogenic diet in ketones benefit people with epilepsy or epileptic disorders, but there's lots of anecdote out there with ketogenic diets on almost all neurological type disorders. Even brain injury, which is a big one, concussions and that could be probably one of the biggest. So why is that? Because obviously it's not specific to the disorder of epilepsy. There's obviously some general thing that it's doing at its core that is benefiting all these issues that you may have with your brain and neurological system. What is that? Why is that happening? Ketones are just a cleaner fuel for us for the brain. Is that what it is? That's a part of it, but with traumatic brain injury, what you have is if you do a scan on someone like a soldier or even a guy that takes a big hit to the head and you look at what's called an FDG PET scan, a glucose PET scan, and that's dim in certain areas, that's your best predictor about how that guy will recover. And if it's a penetrating traumatic brain injury like from an IED or something like that, you have an 85% chance that you're going to have seizures with that because seizures are really common with multiple concussions and even with hard hit traumatic brain injury. So it makes sense to use a diet that we know is more effective than drugs for seizures to do that for TBI. But the faster you restore normal brain energy metabolism, the faster that you're going to recover from traumatic brain injury. And also the neuro inflammation, and I just went to Europe and had a talk on this, now they have a scan that can look at inflammation in the brain. And the diet seems to be working in that regard. And we know ketones have an anti-inflammatory effect. So they may be working not only by restoring normal brain energy metabolism or homeostasis, but suppressing some of the neuro inflammation that's associated with CTE, which is that chronic inflammation that the guys get. In fact, they're NFL, right? And they have a big thing with the NFL with that. Yep. And there's a particular pathway called the NLR P3 Inflammazome. And there was a paper published in Nature Medicine. I actually formulated the diet for Dr. Deep Dixit at Yale. And he showed that it inhibited a specific inflammatory pathway that's kind of tightly associated with neuro inflammation and traumatic brain injury. So that's just an example of one of the pathways independent of metabolism that could be, you know, and maybe that inflammation plays a role in epilepsy. We know that when guys get certain neuro inflammatory disorders, even a virus, you know, various viruses like even like herpes simplex virus or shingles, some, a couple of people were emailing me when they get it, they were getting epilepsy or getting seizures and when they would get a breakout. And we know that that virus causes neuro inflammation. And we know that the ketogenic diet or ketones can suppress that. So it may be working not only through metabolic based mechanisms, which, you know, most people are studying, but we're looking into the immune system and inflammation. Actually, a big part of Andrew Kutnik's research as a PhD student is to look at the immune system and the inflammatory markers that are associated with ketone supplementation. Is glucose metabolism or, you know, working with carbohydrates, is that inherently inflammatory on its own and is removing that part of the process? I mean, that's a tough question to kind of a general thing to ask. But, you know, I'm wondering how much of an effect comes from just the ketones themselves and how much of an effect comes from possibly just the elimination of, you know, carbohydrates? That's a good question. So when you take a hit to the head, or even if you have a neurological disorder, two things will impair glucose metabolism, including lower activity of pyruvate dehydrogenase complex or PDH complex is kind of like the gatekeeper to your metabolism. And with brain injuries, there's also an internalization of the glucose transporter and neurons that would be the glut 3 transporter. So you have less transporter at the membrane, so the cells can't suck up glucose. And if they do suck up glucose, the rate limiting enzyme PDH complex is less active, right? So ketones can bypass that they have a different transporter that can get the ketone across the membrane. And they go, they're metabolized into ATP, our energy currency completely independent of PDH complex. So there's actually a disorder called pyruvate dehydrogenase complex deficiency syndrome. And the only therapy used clinically for kids that have this is the ketogenic diet. So, and we know the prime cause of TBI brain, you know, energy impairment is a dysregulation of PDH and a dysregulation of the transporters at the membrane. They get internalized, you know, they basically get sucked out of the membrane. So the glucose, so the ketones can then restore energy metabolism. So then am I being accurate by saying just kind of what you're saying? So basically, acute trauma reduces this PDH complex and the glut 3, did you say? The glut 3 transporters. So acute trauma reduces those. And if you don't bypass them, it's almost like you're starving. Yeah. And then you have excess glucose. I think maybe that was getting to the question. So you have a surplus of glucose in the cerebrospinal fluid, the CSF. And in your, you know, there's actually this acute insulin resistance to your body of trauma. And that can cause inflammation, something called advanced glycation end products or AEGs. And that can wreak havoc and cause or havoc and cause membrane lipid peroxidation. It can epigenetically suppress, you know, or trigger pro inflammatory pathways. So when you, whenever you have a surplus of glucose floating around in your brain, in your body, that's going to trigger a cascade of inflammatory. Wow. So, so somebody gets hurt, they get injured. We need to hurry up and circumvent their normal energy pathway because it's already, it's already messed up. And if we don't, we're going to get more inflammation, potentially starve, you know, brain cells, starve the body from being able to utilize energy. So you go ketogenic and it bypasses that in those particular circumstances. Are there other things because what I've noticed, this is all anecdote now, but I've been in fitness for a very long time. I've worked with lots and lots of people and some people just seem to thrive on ketogenic type dieting and others don't, it doesn't make a huge difference. And I'm comparing healthy diet to healthy diet. I'm not comparing shitty diet to ketogenic diet, right? But some people seem to do phenomenal on it. Would that, could it, is it safe to say that perhaps they have some of those, so some of those disorders in regards to energy metabolism, like you were talking about, but on a smaller scale, but not from an acute injury, maybe their lifestyle or maybe just that, you know, they're, they're, you know, they have some kind of genetic polymorphism. Yeah. That actually could very well be the case. So, you know, some people are just less carbohydrate tolerant. So they're carbohydrate intolerant. So if they're keep feeding carbohydrates, they have a baseline elevation of high glucose, high insulin, and then they get on a ketogenic diet and it restores them to basically normal health. And some guys will start, you know, making ketones immediately. And we do have a very broad range of fatty acid oxidation enzyme activities. And there's like, you know, for fat oxidation pathways, there's like 12 different enzymes, and you could have variations, different snips that'll determine whether, you know, you're five times more higher activity of HNG coaliase or whatever, some kind of enzyme that either makes ketones or involved in fat oxidation. And we vary across the spectrum in that. And I think some of the technologies that are being developed, you know, you take 23andMe data and you put it into some of these programs that are coming out like Nutritracker and other things will give you insight and information into whether or not, you know, the ketogenic diet may be for you. And I think that's kind of the future. We're not yet there with the technology, but I think we're, it's evolving into that direction where we may be able to predict the diet that may be optimal for us. And then we can kind of start it and maybe some simple physiological or biochemical biomarkers to track whether or not we're adapting to that diet. Well, some people, like the diet just doesn't work for them, and they keep trying it. And it's like, if it's not working for you then, you know, don't stop it. Yeah, I had somebody message me, they're like, yeah, I've been trying a ketogenic diet and I, you know, I'm not pooping every day, and I feel horrible. And I'm like, how long have you been doing like 60 days? I'm like, yeah, you probably should stop. Those weren't enough signs for you. Well, we have to be very careful. I remember even after, so after we had you on the show, or was it before we went ketogenic? Do we go before or dumb? I don't know. Right around that time was either right before we had you right after, you know, we all kind of said, hey, you know, let's, let's run the ketogenic diet for a while and just kind of assess ourselves, what we feel and notice and share with our audience. And we were very fascinated with it. It completely changed my relationship with fats, with carbohydrates, my diets. I mean, I've been in fitness for over 15 years and it's completely flipped it on its head for me. So it was huge for me. And we all kind of shared our stories. And man, after that, it became like, you know, ketogenic diet was like the mind pump diet. And we had to be, we had to like back everybody up like, listen, pump your brakes here. You know, there's, there's a lot of stuff we don't know, it's not for everybody. You know, these are just some of the things that dots that we're connecting and we don't want to come out and say like, this is the official diet. And in fact, none of us actually run like a pure ketogenic diet all the time. That just, like I said, it changed my relationship with fat and carbs. And I feel like that's part of our responsibility is to continue to tell people that as good information is coming out is because, you know, leave it up to all the morons out there, they get a little bit of science or a little bit of information and they fucking run with it, you know, and then create supplements around it and then try and promote the shit out of it and monetize it. So, so I mean, I don't think it's, it's not debatable that the ketogenic diet has got real applications for particular situations, whether it be disease, disease, disorder, acute issues. But let's talk about the healthy average person. What are the potential benefits and detriments or maybe detriments that can come from eating a ketogenic diet? Because most of our audience is just the average person who's just working out, wants to get healthier. What kind of information can we give them in regards to eating this way? Yeah, I would say the ketogenic diet as it's defined clinically, you know, if you look it up on Wikipedia is not the kind of diet that you'd want to follow unless you're, you know, attempting to metabolically manage some kind of like, you know, disorder that's, that's drug resistant or not. In the medical, in the medical ketogenic diet, what's the mackerel breakdown? It's something like 70% fat. It's like 90. It's well, it's 85 to, it's a four to one ratio classical Johns Hopkins, ketogenic diet is about 90% fat and about, yeah, like 8% protein. And that's, you know, for pediatric epilepsy. But as the diet evolved and the applications evolved, Dr. Eric Kosoff, neurologist at Johns Hopkins kind of has brought about the use of the modified Atkins, which I think is kind of what a lot of you guys are following, which is more liberal with protein. So you're, you can upwards of 20, typically 25 and even upwards of 30% protein and the balance being a fat, you know, now we understand, you know, certain fats are better than others and to eliminate certain polyunsaturated plant-based fats and do monounsaturated fats are probably the ideal fat to have and, and carbohydrates at five and even in some cases up to 10% if they are, you know, of a certain fiber content can be, can be added in. But, but so the modified Atkins diet is probably the one that would be most applicable to the general audience. And I think as we age our carbohydrate tolerance decreases as we age and that needs to be recognized. And I think we could probably, you don't, and I was talking to Andrew about this, you know, the other day, if I would go back to, you know, back when I was playing football in high school, if I did a abruptly change to a ketogenic diet, I think my performance would tank and I probably would not be able to put on weight at all. But now that I'm in my 40s, I think a ketogenic diet, my body thrives on it. I mean, I could never go back to eating, you know, growing up an Italian family and shoveling pasta in my mouth almost every night. And I did, I did well on a ketogenic diet. I always stayed lean and my body, I had really high carbohydrate tolerance, you know, my nieces and nephews are basically like mainlining sugar and carbs all day. And they look like little anatomy charts. And so they are obviously very carbohydrate tolerant and do really well. But over the years, I find that, you know, my level of carbohydrate tolerance decreases with time and I just feel better. My energy is sustained longer. I don't have dips. I don't have shifts in my energy level. Is this something that they've seen in any type of study where they can find, they show that that carbohydrate. Right. Does it hit a certain saturation point where now you start to get sort of diminishing returns going forward from that? As far as what? As far as like, I'm on, I'm eating, you know, carbohydrates like primarily and like going through and I'm growing up like eating a ton of carbohydrates is their point where, you know, like you said, like, when does the switch happen? I think it's largely dependent upon your activity level, obviously, but I think hormones too. I mean, your insulin sensitivity when you're growing up through the teenage years, especially is just really high even through your early twenties and everything. So your body is much more responsive to like anabolic hormones. So protein synthesis is just happening at a faster rate. You're repairing muscle tissue faster. So I think all those energy dependent processes are sensitive to glucose and insulin and you're more likely to have a better glucose disposal and insulin sensitivity when you're younger and growing and more active. And as we age and start sitting behind our desks and doing, you know, 90% of the day is basically inactive. Either we're sleeping or behind the desk and 10% we're active. That's kind of, well, maybe the kids today are like that. But that's when I was growing up, I was pretty much half, you know, more than half a day, I was just running around doing stuff, working on the farm, like constantly active. Do you think maybe that it's just a, just a chronic, like, you know, because I grew up in a Italian family too. And it's like, I just ate carbohydrates all the time. And maybe after a while, my body's like, no, that's enough, you know? And I think our mitochondrial capacity to decreases with time. And it's inevitable. I mean, it's part of the aging process, right? But I think what's interesting about the ketogenic diet, when you force your body away from glycolysis, away from sugar, it's forced to metabolize fats and ketones for energy. And when you do that, and it's well established that it's a stress initially, but your body, there's mitochondrial biosynthesis. So you have more mitochondria over time and the efficiency of the mitochondria increases. There's more mitochondrial biogenesis. So these are real things that happen over time. It's been shown in animal models and athletes too. It's kind of the effect of exercise, but even independent of exercise. If you were to shift the macronutrient profile of the diet to higher in fats, you make more mitochondria. And that's, I consider that like energy reserves. So by having more mitochondria, by forcing your mitochondria to work harder, the hormetic response or whatever you want to, you have more metabolic flexibility. You can go back to eating carbs and glucose. And then when you shift back to fats again, you have the mitochondria there that are responsible for beta-oxidation of fats to make energy. So I think training your body to burn fat and ketones for energy and periodically using glucose under certain situations, I think, would be ideal for the average person. That's where you're getting at, like an average person. Yeah. And I totally, that's how I do it now. And I had some autoimmune issues years ago, and I found that eating more fats and less carbohydrates just made me feel better. And I've gradually, you know, moved towards a, you know, being in ketosis a lot of the times, but I did find that if I went out and in every once in a while, I would get boosts and performance in the gym and just all of a sudden I would get these great effects from the ketogenic diet again, like I had before. And from an evolutionary standpoint, it kind of makes sense, right? Like why would we have the ability to use both, you know, glucose and ketones? Like it seems like we found, if we found fruit and we found tubers, we're going to eat the hell out of them. And if we didn't, then we just ate the meat that was around us. So would you say that's beneficial to go back and forth? And yeah, okay. Our body knows what to do. I think there's a lot of confusion out there that if you do eat this way and then go back, you know, you'll have insulin resistance or whatever. But I think it's kind of good to stay for the average person unless you're managing like, you know, some kind of disorder to switch in and out. And yeah, I think we're designed to do that. And I think our bodies kind of work better when there's relative changes. Like, and I think it's better to adapt in that way. We're much more metabolically flexible. Tom, when you look at the younger generation coming up as a whole, right? And I know everyone's individualized here. But as a whole, what's the advice you give to someone like that as far as, you know, maybe the eating habits that they're creating, you know, in their teens and 20 years old, what do you see is a problem or that could become a problem for them? And how would you advise somebody in that age group that what would you say? Saying for like the just saying, well, yeah, because we know like, I mean, obesity is on the rise. We have more information out there, right? We have the science is better, but yet we're, we're, this is, yeah, we're getting to me, I feel like, okay, well, then what's going on here? This is makes sense to me. So someone with that's a scientist like you that does a lot of research and understands effective carbohydrates and fats and the benefits of ketogenic diet, you know, and if you were advising a younger person that's coming up and, you know, eating Captain Crunch for breakfast and then pop tart before he does his workout and then smash in his, you know, protein bar. And I mean, this is kind of like his day, which was a lot of how I ate, you know, growing up, you know, what would you say to someone like that? Well, I would look at what you're doing and kind of say, you know, how's that working for you? And then analyzing what they're doing and to bring them back. I mean, we just put in a grant in El Paso because there's a big problem there with the community of the kids and the adult population, obesity is skyrocketing. And it's kind of like, it's very hard to get like whole foods and packaged foods and sugary drinks are just off the charts there. So it represents a really big problem. So you'd have to look at the people and actually look specifically at what they're doing, what they're putting into their bodies and their activity levels. It's multifactorial, but a lot of it has to do um, many people kind of know, well, not always know what to do, but it's their relationship, it's their psychological relationship with food. Like they may not necessarily need a nutritionist, they may need like a nutritional psychotherapist. Like they need to change their relationship that they have with their food because they are going to, you know, their go to comfort foods are the things that they gravitate towards later on. Do you think it's purely psychological or do you think that some of these foods have addictive properties to them too? The physiological changes and the neuropharmacology of the brain literally changes in ways that make us psychologically dependent upon foods and even generally speaking macronutrient ratios of foods. Like, you know, so you could say it's engineered somewhat, right? Yeah. Yeah. Oh, come on. You know how much money these masses. This was a little area that we didn't see quite eye to eye with Lane. I know we're all good friends with Lane and Sal loves the jab at him in this area. We all are a little good friends. I talked to Lane about this a lot. Yeah. Yeah. This is what, yeah, what, tell me what your thoughts on this. Well, uh, there's no doubt. And I think Lane will even agree that, so my perspective is when it comes to, you know, and the big thing is kind of weight loss and body composition changes, you know, getting leaner and that comes down to being able to control, you know, the psychology of your food and that comes down to appetite and being satiated. And I think Lane will even agree and many coaches out there need to look at the data and will agree that if you're following a diet that causes less post-prandial excursions in glucose and insulin, it's going to change your appetite. So our desire to eat or to binge, I would say, which is a problem if we're calorie restricting for any period of time, is a result of a hypoglycemic event. Like if we have like normal blood glucose and do not dip into hypoglycemic zones, we're not going to have these cravings that really send us over the edge. And I think you could do that with, you know, and if it fits your macros, kind of metabolic. You don't feel like that's kind of flirting with it though? Like you can do that, but some people can do that if you have willpower, but the ketogenic diet or just, you don't even have to be ketogenic, just, you know, carbohydrate restriction, you know, low carbs, moderate fat, even in high protein diet would work because protein has a satiating effect too. But the carbohydrate restriction component seems to be really important at least initially to kind of fix people's metabolism and then they can titrate carbs back in depending on their goals or what they want to do, but that's to culprit. And it's controlling appetite. And there seems to be some differences between, even between ethnicities, there's some like polymorphisms like Native Americans and Hispanics, for example, seem to have much high, well, they do statistically, much higher rates of things like diabetes and insulin resistance, eating the same Western diet than, you know, that the rest of Americans do. Do you guys ever look into that because I'm, you know, there's some theories, right, that maybe the Native Americans were hunter-gatherers for longer, and they weren't into, you know, they didn't go through the agricultural illusion like we did. And so, you know, their bodies don't respond the same. And they're the population really, the group that I was working with that we put in together. In El Paso? Yeah, they, you know, it's such a challenge for these people, the families and the kids too, it becomes such a stress for them to count their calories. So we talk about, you know, flexible dieting, but if you're flexible dieting and eating the same foods, you know, and you're hungry all the time, so the good thing about carbohydrate restriction of the ketogenic diet, you lose weight inadvertently. You're not even trying to do it. Like it normalizes your appetite and you become satiated to the point where your brain auto regulates and you eat according to your body's needs or your energy levels. Whereas if you're spiking glucose a couple times a day, even with a perfect flexible dieting macronutrient ratio, you're still, you know, spiking glucose more if it's a carbohydrate-based diet and you're getting these postprandial dips in glucose that's triggering hunger. And it's the, in that population that you just mentioned that are classically insulin-resistant for a variety of reasons, mostly genetically to some point, but there's some kind of behavioral things to there. It just makes sense to use this approach. Or you can, you know, create a flexible dieting scenario where you have a toolbox of different approaches that you could do and just do a flexible dieting scenario with a low carb or ketogenic diet. And I know Lane is very interested in doing that too. And the guys who practice this are becoming more interested in it because they're reaching out and contacting me. In fact, you know, when you say that, I could tell you right now, trying to gain weight, eating ketogenic is much more difficult to do. And in fact, one of the reasons why I go out of it sometimes is that I'll just keep losing weight. And is that primarily, is it just the appetite suppression or is this, is there also another fat burning or weight loss thing that's going on there that's causing, you know, your body to want to lose weight? I know that's a million dollar question, right? Yeah, I think, you know, I've probably lost a good 20 pounds since I've been doing this, but then again, my work has become much more intense. I spend long days in the lab and I generally eat two meals instead of trying to force feed six or eight per day. But I have, it's been really amazing the amount of muscle and strength I can maintain doing hardly any like getting hardly getting to the gym at all or eating very minimal. So when it comes to losing, you know, with the ketogenic diet, if you are losing weight, the thing to do is to increase your protein and keep kind of your carb fat ratio the same or actually just start putting in titrating in more protein in and around your workouts, I think can can help a lot around the days, you know, that I always say about the 12 hours after your workout is when you really want to drive protein synthesis. Okay, let's talk about exogenous ketones because I know you're like deep in that in that particular realm of this. What are you guys looking at right now with exogenous ketones? What are the applications for taking just a ketone supplement? Yeah, the original application was, was pretty, I guess esoteric, I guess you would say it would, it was for CNS oxygen toxicity seizures. And that's a limitation of Navy SEAL divers or special operations divers or even recreational divers that use a close circuit rebreather. What was the, you gave a number, I think I heard you talk about what's the, how many of those guys would experience that before you started doing this research? Well, the problem is if they do report it, they kind of get in trouble and they may, they may pull them. So it's, it's grossly underreported. So what I've, you know, done is kind of connect with the rebreather diving community, these tech divers that are using the close circuit rebreathers, and they say it's happening all the time, you know, they're getting like, you know, eye twitches or kind of weird auras and have to surface quick or even on the fly, change their breathing gas mixtures. It varies. You can, you can prevent it pretty easily, actually if you just dive within the limits of your, and the Navy has certain limits as far as how deep you are at just 10, at just 50 feet of seawater, you can get a, you can get a seizure in 10 minutes. And that's not, but with these rebreathers at the seals you use, they just, you typically have to stay very shallow just to stay out of, and there's no bubble, so you can sneak up on guys and shoot them. And that's the idea. But sometimes if you're taking fire from a 50 caliber gun, or you got to go down and put a, and put a, a mine on a ship, or, you know, there was a dozen to different scenarios guys would tell me about, or they would just have to, because the enemy is there, they have to stay under longer. They, they can't surface. So if you're, you're, you're dive computer, the table say, hey, you got to go up, but the enemy is there with a gun, you know, you got to stay down. So, so in, in those situations that can be fatal to the mission and fatal to the guy too, right? Because a seizure underwater is, so oxygen toxicity seizures in and of themselves are not detrimental if you're in a hyperbaric chamber, you know, because you, as soon as you lower the partial pressure of oxygen by just putting an air in place of 100% oxygen, you knock right out of the seizure. So if you're diving, all that means is you just need to surface up. So it's very under reported to answer your question. And it's being studied now, we studied it in rats and showed that you could feed rats a high carbohydrate diet and give them a ketone ester. And it would increase their latency to seizure 575%. So instead of seizing in 10 minutes, you could go over an hour at 132 feet of seawater, which is five atmospheres. And, and so we started studying that. And now we're looking into now you have something, it's not an anti-epileptic drug, which would make your thinking foggy and slow you down physically. But it's an energy molecule that you can consume that protects your brain in that environment. And it's also feeding your body a source of energy that can potentially enhance performance. So as you know, like the cycling community is all over this, and we're doing experiments in rats, we put them on like a treadmill like device, like a rotor rod, and they, and when we get the dosage and the formula, right, they can run faster and longer. And it just becomes like another fuel like creatin in regards to, you know, intense strength training, its ketones are like the next creatin for, you know, a range of different things. I saw after we talked to you, I actually bought some online and I noticed mainly was an endurance boost. I just work out and work out and work out and I felt like I keep going. So that works for people who eat carbohydrates. So if I'm meeting a regular diet, I could take exogenous ketones and go cycle. And I'm going to notice what they're showing is that you're getting a boost in endurance. So you don't need to be on a ketogenic diet to notice that? Well, that's studies that we need to do, right? So the animal work supports that. And the anecdote supports a lot of friends that do it that way. Yeah, there's the elite level cyclists, you know, that will are experimenting with this stuff. And there's a few couple publications that are out looking at it and, you know, pretty high impact journals like cell metabolism that show kind of an increase in time to exhaustion and things like that. It needs to be further, you know, explored as to what is the, and there's dozens of different types of ketone supplements out there, which make it even more interesting. Because I think the real benefits come in formulating something that's not just ketones, but ketones and other energy metabolites and cofactors that make those energy metabolites be able to be utilized more efficiently in the cells. Interesting. So that's, we're really excited about formulating things. Yeah, because right now on the market, I think the one I got was just beta hydroxybutyrate, right, just in salt. And in the studies, you guys are using something else? Well, we use, you can make, you can combine beta hydroxybutyrate to many different molecules, you know, and call it a salt. If it's combined with sodium, it's a sodium salt. And you could combine it with potassium, magnesium, any monovalent or divalent cation, or even amino acids. So that really, and if you spread the beta hydroxybutyrate across many different electrolytes or minerals and even amino acids, that allows you to be able to take in more of it. Because if you just make a sodium one, you're getting a bit of a sodium overload, or if you make a magnesium one, you're going to be crapping it out. Oh, wow. Yeah, so it's that. That's exciting. Formulated, you know, the ketogenic diet makes you deficient in some things like potassium, for example, and even magnesium. I was deficient in magnesium, and until I started supplementing, and I felt much better, I didn't get cramps. And some of the supplements on the market are combining beta hydroxybutyrate with magnesium, and that shot my magnesium levels up really well in the top end of normal, where I was in the bottom end of normal. And the magnesium supplements on the market are kind of pricey, and the ones that are cheap like magnesium oxide didn't do anything to my magnesium level. Oh, so you were actually testing your blood to see if it. Yeah, tested my minerals and things like that. So you could formulate a ketone supplement that would be a great supplement to the ketogenic diet if you're a low carb diet. So if you're doing a low carb diet, but not hitting ketone levels to a point where they would be kind of ergogenic in a way, you can supplement with ketones and still get the benefit of low carb diet and ketone supplement. I'm also reading a lot of people online talking about a new tropic effect from supplementing with, well, okay, so it's been around for a long time now, where you hear people saying, Oh my God, I went, you know, I started eating ketogenic, and I can think clear, I feel sharper. So you've got all these brain hackers who we... Do you think it's from the ketones or do you think it's because of the suppressing the carbohydrates? Which one do you think it's? Yeah, that's a good point. So if you're putting in energy or calories in the form of ketones, people need to recognize that if they're consuming these ketone supplements, it is a source of calories. Even though the FDA doesn't really have it, you know, it's not in the food label. It doesn't say it. When you buy them, you're like, Oh, there's no calories in them. Yeah. Yeah. And I think marketers try to play that up. But yeah, you are consuming calories and your appetite might go down because you're consuming, you know, calories, right? Your body has kind of energy sensors. So the neurological effects could be due to a number of different factors. Like I said, Stephen Kunane in Canada, he does a dual PET scan. I talked about a glucose PET scan, an FDG PET scan. Well, he does a ketone PET scan. So he can image the brain and the fluorescent intensity of the signal reflects brain ketone utilization. And he can do a glucose and a ketone PET scan and show that the brain can use both fuels very efficiently. As we age, we have impaired glucose metabolism as we age, but that's not the case for ketones. So our ability to use ketones as brain fuel does not change as we age as it does with glucose. So I think the people that may be, benefit from this most are the age population or people with some kind of impairment, or the special operations community, or if we're... So a lot of what I do is studying the physiology and the neuroscience of extreme environments, whether that be like altitude or space or the hyperbaric environment. In that case, ketones shine. They seem to shine because they can suppress oxidative stress and they preserve brain energy metabolism and function even in the face of an oxidative challenge or an extreme environment. But when it comes to a normal, healthy person, I think the jury's still out as to whether it's beneficial. There's anecdotal reports out there. And I can even say myself, I noticed that if I'm a little bit hungry during the middle of the day or something, I fasted quite a bit and I take ketone supplements without a doubt. I mean, my energy, I'm more focused. I can kind of work more productive. So it may just be that their brains weren't just working very well with glucose. And so now on the ketogenic diet, it works well. They've got good energy and they feel a boost, but not necessarily because it's a boost on its own. Yep. And there's other... As a scientist, I have to critique even these anecdotal reports and even myself. So if I was to give an equal amount of sodium and fluids and it increases my blood volume, I get better circulation to the brain and even a little boost to my sympathetic nervous system when you get a little bit of sodium and fluids in you. And then that could be stimulating. So you have to tease out all these effects. I'm glad you said that because this is the thing that always worries me. When I'm hearing us talk about this right now is we get this little bit of science and good information that we're learning. Now all of a sudden, the market takes it. And I can argue or I could pitch that if this supplement, it could help increase stamina and endurance type runners that it could help you build muscle because now you could go longer and go harder and increase volume. So now I can sell it as like a muscle building supplement or even possibly a fat burning supplement when really it's like splitting hairs on how much it's really beneficial, especially if all the other shit in your life is all fucked up. Like you're not drinking enough water, your sodium's off, your macros are all fucked up. But now you're buying this $50 supplement because you think it's going to help you burn fat or build muscle. Yeah. Yeah. So that's why we really need to studies and we harp on that all the time. In regards to building muscle, there is some data to show that ketones can be anabolic in some ways. Oh, that's a big one. Yeah. What is it showing? What is the science showing? Well, it depends. There was a study in humans actually where they gave like IV ketones and looked at leucine metabolism and protein synthesis and showed that it went up in the presence of an IV administration of sodium beta hydroxybutyrate. And there was a couple studies in animal models, one in an animal model of muscular dystrophy that showed that acetylacetate which breaks down from beta hydroxybutyrate. And we can also, we develop forms of acetylacetate. And we think it's important to get a ratio of acetylacetate to beta hydroxybutyrate in the blood to get optimal effects. That acetylacetate can mitigate the muscle loss and even aid and muscle regeneration in particular disease models. And it was some preliminary reports on animal models showing that. So that's something that we want to study actually. Andrew Kutnick, the PhD student in the lab is focusing on mitigating cancer muscle wasting called cancer catechia. And we are developing a mitigation strategy to prevent that. And from an evolutionary perspective, if we're fasting, our body will shift over from using glucose to fatty acids and ketones for fuel. The brain does not readily get long chain fatty acids as a source of energy. So if we didn't make ketones, we would catabolize, we would break down a lot of the gluconeogenic amino acids from our body, namely our skeletal muscle, because that's the biggest source of it. So we would start chopping up all these amino acids to mean the body has very, very powerful homeostatic mechanisms to main blood glucose. So it will chew up all your muscle to keep blood glucose to send energy to the brain. What prevents that is the formation of ketones in the liver. So if the ketones are elevated in the blood, then they become extremely anti-catabolic. And that's the evolutionary, one of the main purposes is to supply, your brain is like 3% of your body weight, but it sucks up 20 to, in some cases, 25 and 30% of your energy. So it's a massive energy sink. And your body will do everything in its power to prevent it from being energy deprived. So if you have ketones elevated, that's a tremendous buffer from catabolizing amino acids from your muscle. So they're very anti-catabolic in that sense. Wow. So let's talk about current research right now. What are you, are you able to talk about what you're working on now? Because I know a lot of the stuff you do in the past, you've worked with the military with the Navy SEALs. Yeah, I'd love to talk about what you're working with. Yeah, yeah. Can you go on to some of that? Yeah. So we have, I would say, you know, a half dozen or more different kind of like active projects. The big one that kicked everything off was oxygen toxicity seizures. And that was done in a sprag dolly rat model where we just, you know, gave ketone esters and looked at the effects of mitigating oxygen toxicity seizures. And that work has recently translated to projects that we're writing up and working on getting funding for, because the agency supports its Office of Navy Research and NAVSEE, it's part of the Department of Defense, to do an analogous study in humans where they are in a hyperbaric chamber and they are exercising at a level of hyperbaric oxygen that would be equivalent to, you know, various missions using a closed circuit rebreather and looking at oxygen toxicity and actually taking these guys to seizures. Or they actually have physiological biomarkers that they can detect that are early indicators that you're going to have a seizure. Interesting. So they can predict it like, okay, this guy's about to have a seizure. Yeah. So they focus on that, but they also have guys, so they're underwater sort of exercising but with their head above water to catch them so they don't get. So these are experiments that are kind of being, are in the process now of getting funding and will be done at Duke University in collaboration with our lab. So it's a translation of our preclinical animal work to the human populations, which we've been working on. And some of the more potent ketone supplements are not yet FDA approved. So we actually, we're going to use the ketogenic diet because when I first got into this, there was such a stigma on the ketogenic diet killing athletic performance that the Navy didn't even want to touch it. But now, as some of the data is emerging, it's showing that well, it may not be so detrimental to performance. It actually may be helpful. So they kind of warmed up to the idea of using a modified Atkins diet to produce ketones in addition to some commercially available ketone supplements that can be formulated and to put these guys on and to do the study. So oxygen toxicity is one and also exercise performance. So warfighter performance is a big one. And that's our program officer is actually the program officer for undersea medicine and also like warfighter performance. So he's interested in basically finding out what's the optimal ketone supplement, what's the optimal nutritional ketosis state that can optimize performance under a range of environmental extremes, whether it be hypoxia to hyperoxia to even hyperthermia or hypothermia has been a topic of one of the recent meetings. Yeah. Is there any benefit to eating ketogenic when you're in those extreme temperatures? Well, some of the animal data suggests that when your body is adapted to a ketogenic diet, you may have some better thermotolerance and under both extremes. Interesting. But it has not been tested experimentally yet in like it controlled trials in humans. So these are things that we're moving towards. And is there any anecdote out there or any chatter? Because I think there's a lot of these extreme athletes that are doing these cold dips and cold and hot contrasts. Is anybody saying like, hey, ketogenic diet helps me with that? I haven't paid attention, so I don't know. So I'm just curious. Yeah. You do get a thermogenic effect from certain types of fatty acids, even medium chain triglycerides can stimulate thermogenesis in some ways. But nothing really robust. It's all like a very little effect. We just had a meeting on hypothermia and how to mitigate it. And kind of the best things out there from the literature was like caffeine, a pheasant stack. Yeah, it was like... Masal constrictors? Yeah. And just stimulating metabolism in general. Catecholamine production. Yeah. And just internal oxygen consumption. But if you, when you're stimulating metabolism, it's a double edged source because you are consuming more oxygen too. So you increase oxygen consumption, which is not a great thing in some situations. And central nervous system stimulants can make you more susceptible to CNS oxygen toxicity. So... Oh, I don't know that. Yeah. Like if you take a big hit of a stimulant, right? Well, we did a study. It was funded by Diver's Alert Network using pseudoephedrine, racemic aphedrine. And the dose had to be high. But if the dose was, if you downed about four or five times the recommended dose and you went diving, you could have a seizure faster. And people do abuse aphedrine in that way. And divers, the worst thing for a diver is to have sinus congestion. And you want your eustachian tubes and your sinuses to get out. So they must use pseudoephedrine like crazy. Yeah. When we went, so I'm a diver. And when we would do, when we would be diving, like everybody would, you know, hand around their package of pseudoephedrine and people pop pseudoephedrine before getting into the water because they don't want, you could pop your eardrums if you're eustachian tubes or clocks. So it's very common to take these de-congestants when you dive. And they are seeing a stimulants, you know, like aphedrine. It's a pretty powerful stimulants. That's fascinating. So if you take pseudoephedrine and you're going diving, it's probably a good idea to be on a ketogenic diet or take some ketones, kind of offset that to offset that whole situation. So something pops up in my head when we talk about supplementing with ketones and exogenous ketones. Do we see individual variances when people go on ketogenic diets in terms of the types and amounts of ketones that they're producing? Because there's a lot, there's different ketones that people run off of, right? And I would imagine that one of the difficulties in creating a supplement would be to kind of hit what the body would naturally produce or what the, you know, because you've got Betihydroxybutyrate and you've got some other stuff going on. Do we see individual variances where this person's in ketosis, but we see higher levels of these ketones and, you know, this is going on with him and this person over here is a little different? Or is it more general than that? So to answer your question, yeah, there is big variations. So I guess the important thing from a practical perspective is how do we use different tools to figure out, you know, if we are making ketones well or how to optimize it for us personally. And I think that's what we're really interested in doing that. And we also know that the body has about a dozen different ketogenic enzymes, you know, one is thiolase and one is HMG-CoA-Liase. And these enzyme activities vary in different people and will be very important for their adaptation to a ketogenic diet. And in some ways you can up-regulate the enzymes over time. But I think the best indicator is kind of like your performance and how you feel, but also the measurement of urine ketones, which would be acetoacetate or blood Betihydroxybutyrate, which can be measured by a commercial meter and Abbots lab precision extra or a neo. And if you are just feeling typically, if you feel good on a ketogenic diet, and I would basically just stop what I'm doing if I felt really good and then check my ketones and I consistently, instead of checking my ketones and trying to like, you know, saying, okay, I feel good because my ketones are high, I would kind of stop when I felt most energetic and most lucid. And I consistently got a certain ketone range and I would tell people to do the same thing, follow ketogenic diet. And if you feel like crap, well, measure your glucose and ketones at that point in time. And that's probably areas where you don't want to be in. Whereas when you feel most energetic, have the best stamina, try to get a metabolic snapshot of what that is and try to figure out what you did and how to achieve that state. And those biomarkers that made you achieve that physiological psychological state. Now, I know for a lot of people when they reduce carbohydrates and bump up fats, and even if they do ketogenic or modified keto, you tend to see the literature at least shows that you see lots of improvements in blood markers like cholesterol and triglycerides and better insulin sensitivity. However, there are cases where you've got, you'll put people on a ketogenic diet and their lipids just go crazy and it just doesn't look good. Why is that? And are these people obviously should not eat a higher fat diet? Or is it the type of fats that they're eating that they may need to change? Well, I had that too. I got an NMR lipid profile, which looked at everything and my LDL P was elevated. My LDL was elevated. So really high. And that's not the case anymore. But when I did that test, I was eating about 60% of my fat intake was dairy fat. And over the course now, maybe about 10 or 15% is dairy fat. And I was just showing Andrew my numbers yesterday. My total cholesterol, it was 300 and now it's 180. And my triglycerides are like 50 or 60 or something like that. Just by dropping down the dairy. The dairy fat and adding more monounsaturated fat. So the composition of the fat plays a big role and also maybe adaptation too. So I purposely, I did that pricey lipid profile test, which my insurance didn't cover. So I took a big hit to my part. So it was like $1,500 test. Is this the one where they look at like the size of the LDL particles? Yeah. And there was like lots of red flags there. And I followed it for, I consistently ate what I did. The experiment was like eating my keto mousse, which was like basically a quart of sour cream a day. So I was getting like 250 grams of that. Sounds fucking awesome. And my weight didn't even really go up that much. Which is interesting because I am a good fat oxidizer. But no other bio marker or what I consider a bio marker of general health was elevated. My C reactive protein was like 0.1 in a range. So everything else was great. My triglycerides were even pretty good. They bumped up a little bit to maybe 65 or 70. But on a general scale, that was really good. My glucose was good. Every other, my blood pressure, heart, like all other things that I think are most important biomarkers of health were excellent. So what, you know, and I talked to the experts that are leading lipidologists on this. And they said, oh yeah, that's, you know, that's, these are numbers that you want to bring down. But then I question them, everything that we know about, you know, LDL and LDL, you know, little particle size and thing that, we understand it in the context of a regular diet. We do not understand what these numbers mean in the context of a ketogenic diet, which is radically different than the eating pattern of a normal diet. Because that same number could be horrible. What do they say to you when you say that? Do they, do they respond? What do they respond to you? They say that's a really good point. And, and they say, you know, well, well, you have to ask the question of why, why is it elevated? And I think, you know, the LDL particle are like little boats that carry around cholesterol and even triglycerides. And if you're eating, if you're pounding tons of fat, what you do, you know, on especially a classical age, you're going to need more little boats in there to carry around the fat. So I think it's the body's way to just upregulate a transport mechanism for fat and cholesterol and things that you're eating. So, and I think there's more, maybe turnover too, I think your adipose tissue kind of opens up where you have more fats coming in and being stored, but you have more fats going out and being, so there's just like more rapid turnover of triglyceride in the adipose and probably in the liver and other intraorgan kind of movement of fatty acids too, as you adapt to it. So I think that's the reason, but we don't know. I mean, classically though, those markers are correlated with- And that's why you change your diet because you're like, well, we don't know, but I want to make sure. Yep, we don't know. And I basically, I'm trying to figure out, you know, what is, people ask like, what should my fat ratio be? If you were to, you know, take a biopsy of someone adipose and look at the primary fat, which is in the adipose, it would be monoinsaturated fat. So I think from a very simplistic point of view, it would make sense to kind of eat the types of fats that our body prefers to store as an energy source for use of energy source. So a lot of people think like a steak is like pure saturated fat, but if you look at a steak, it's mostly monoinsaturated fat. Especially if it's grass-fed, you see a little bit of a different fatty acid profile. Yep, that changes it too. And I actually was talking to this a few years ago with Donald Lehman, who is a, or Lane Norton's PhD advisor on fatty acid composition of different protein sources. And he was like, it was his impression that a steak is actually perfect, you know, kind of a fat source. I love this. You just made my day. Yeah, the talk was basically about, and this was, goes back years ago, about the demonization of saturated fat and what types of fats would be ideal. I also think it's interesting that when you look at cholesterol numbers, very, very high cholesterol is correlated with early death, but it's also correlated with longevity. Some of the oldest people. Yeah, how worthless are the basic cholesterol studies? I mean, a test that a doctor gives you nowadays, is it worthless now from what we know now? Yeah, I definitely, I mean, it's much more important to focus on your triglycerides. If your triglycerides are elevated, that basically means that your fat metabolism sucks. So if you have all these fats floating around, they have the potential to be oxidized and wreak havoc on different things. But I think, you know, your triglyceride number, that tells a story. And the fastest way to lower your triglycerides is to eliminate or reduce carbohydrates, because if you have sugar and glucose in your blood, then your body's not going to suck up the triglycerides and use that for fuel if it has glucose. So there's the kind of a competition there. So if you lower glucose that forces your body to dispose of essentially the triglycerides that are floating around in your system and to oxidize those fuel. I always found it fascinating with cholesterol. There was a little stint there, where I did a lot of research and reading myself on the internet. And it was crazy, because I found people who had relatively or by current standards, high cholesterol, so over the over 200, that's like the people who are like the centarians, they all tend to have this kind of higher cholesterol or at least those that do get less infections or stronger, have more mobility. And then LDL, although high LDL was connected to heart disease, it was also connected to stronger immune system, like people didn't get infections as often with high LDL. And people don't realize that low cholesterol, like really low numbers, are strongly connected to mental issues like depression. So it's an interesting all cause mortality. So cholesterol is an essential building block. Your brain is like a big chunk of cholesterol, fat and cholesterol and phospholipids. So it would make sense that it would make real sense that if you're deficient in cholesterol, that could be a very serious thing. And when it's high, I'm not convinced that that's a bad thing if your LDL is high. It's good to have your HDL elevated to pretty, I'm pretty convinced that low HDL can contribute to heart attacks, just seeing some of the numbers out there. There's various things like anabolic can really push your HDL down into like even the single digits sometimes. So I think it's really important to keep your healthy HDL level to like 60, 70, 80, even 100. So who are the kind of people that you would say you could say right now that probably shouldn't eat a ketogenic type diet? Is there any kinds of people that you'd say, okay, look, I don't think I'd recommend this to you. Or is it more of a try at first and then determine? I would say all kids and teens and maybe even early 20s that don't have a problem, you know, are not overtly obese or insulin resistant, could probably do fine just on a higher carbohydrate diet. But I think generally people who feel like they have a preoccupation with food too, and they have to eat a lot, and they're always hungry. So I have people who come up to me and it's like, I got to eat all the time. And it's kind of liberating to eat a diet that's higher in fat and protein and not be hungry all the time. So if that's something that I think appeals to them, then which, you know, should appeal to people who don't want to be kind of hungry all the time. I think they should at least give it a try. So Dom, I want to pivot a little bit because if I let Sal, we will talk about studies for four hours here. And I always like to give our audience a little more of, you know, your personal background and maybe your business mind and sense. And you know, tell me, like, I have no idea like, how does a scientist get paid? How do you how do you make a living being a scientist? Because I feel like there's not a lot of ways you guys, how do you guys do that? How does it work? How do you monetize? Yeah, it's not to monetize. Yeah. So we get a modest salary, you know, as an educator. Well, I guess I'll take a step back. So as a PhD student, well, I'm extremely fortunate, the last, you know, two PhD students in my lab, Nathan Ward and Andrew Kutnik are presidential fellows from our university, which is a very prestigious award that you get, you know, as a fellow and basically you have a full ride. So and that as a principal investigator running a lab, the biggest hit to your budget is actually when you take on a PhD student to do research in the lab, and they really are kind of steering the wheel they're into trenches, you have to pay their stipend, which is like 25 to $27,000 a year, you have to pay their tuition, you have to pay their health insurance, it ends up being like 40, you know, 45,000 in the business world, that's not much. But to a scientist who you have multiple students that that ends up being a lot. So we have to get that money from federal grants or if we're lucky enough grants from industry. So as a student, you know, I was funded from a fellowship too, but it was a fellowship through not a presidential fellowship, but one through my advisor. And it's a very modest income just enough to live on basically like 25, 30,000. And then as a postdoc, you get bumped up to maybe after you finish kind of like analogous to a residency, if you do your MD, you're getting paid maybe about 40 to 45,000. And that money, you start after your PhD, you work as a postdoctoral fellow. And that period is your period to shine and to establish yourself as an independent investigator. So you pick a project and you just keep writing grants and writing grants until you get funding to fund your own salary. And it's kind of- Sounds daunting. 12, 16 hour days of research, not only in the lab, are you doing research and running your own experiments, but your PI typically has a little bit of money to get you started, but basically says go do the research and write grants to get your own funding, because I don't want to keep having to fund you all the time. And if you move on and then get, I was lucky enough to get funding through the Office of Navy Research to do it. I had submitted grants to many different agencies, American Long Association, American Heart Association, even NIH, and they all got rejected. But then I wrote a proposal to do something that was really high risk, but high reward. And it was to develop hyperbaric atomic force microscopy, which is a type of microscopy that allows you to like zoom in on cells and get ultra high resolution scans, like an electron microscope, but you could do it on living tissue. And it was kind of like an out of the box. And we were going to take this technology, and instead in using it on like Silicon Valley applications like materials, we were going to like image living cells with it. And then not only that, we're going to take this technology and stick it inside a hyperbaric chamber that could simulate all sorts of environmental conditions, whether it be the top of a mountain or the undersea environment. Now, are you watching the cells real time with this? Yeah, so you can you can image cells real time the tip with an atomic force microscope, the tip actually interacts with the sample. So you can like functionalize the tip, you can push in on the membrane and do see what's going on. Membrane viscoelastic changes. And so with my postdoctoral fellowship, I just I tended, I did something, I got funding to do a pretty novel project. And that was a stepping stone to to other grants and to work with other investigators who wanted to use this kind of technology. And then working with the Office of Navy Research, because they funded the project, they're more likely to fund you to use the tool that you developed. So that led to another, a larger grant, which led to a larger grant and a larger grant. And then I moved from a postdoc to what's called a research assistant professor, but on soft money, which means the university was not paying me. I was paying all my salary and paying even the people under me and paying for my experiments. Yeah, so completely soft money. And it sounds like a pain in the ass, dude. Yeah, you're always like on edge, because if you lose your funding, they like kick you out. So nobody goes into this to become rich. You've been in the game for a long time. And you can't your salary set, the school basically says, well, you can pay yourself that amount. And it's just enough. You really get supplemental income. But then I transitioned into what was called a tenure track position. And in that five years, if you publish X amount of papers, if you pull in X amount of research dollars, typically in the millions they want, if you teach X amount of classes and serve on X amount of committees, service to, and there's this metric that you have to hit. And if you hit all that within a five year timeframe, and that timeframe does seem very compressed, you can get promoted to tenure. And I recently got that like last year. So in that tenure, what that tenure does is they basically, the school covers your salary up to 50 to 70% of your salary. And then you have to pay the rest of it through grants, but it secures your position at the school where you have to do something illegal for them to like fire you or something completely out of line. So that's like a big, that's like kind of the thing that people going in academia, the scientists try to do. They try to get into a tenure track position and hope that all goes well. And then when you come up for tenure, you have to submit this huge packet of information that a committee who evaluates. It's no joke, man. And how many times is any of this like intellectual property that you can keep for yourself? Or do you have to sort of give this away to the people giving you grants? That's a really good question. So depending on the agency that's funding you, if it's a company or an industry, the contract may say in the contract that they have all the rights to the intellectual property. And the Department of Defense surprisingly kind of gives up all the intellectual property to the university. So I can be an inventor, which we do have a number of patents, like almost up to 10 patents now. And not all of them are licensed, just some of them are, but the school essentially owns that intellectual property. You are an inventor on it. And then they have their technology transfer team works with all the interested parties, and they basically negotiate who's going to get the license for what kind of application. It's very different if it's going to be a medical application, a military application, or like a general use. Just sort of defining for those. Yeah, general kind of use. Just doing stuff like this help, like getting on podcasts. And because you've been on the circuit now, I've heard you talk, I've seen you talk on YouTube, Ted talks, and you're going a lot of podcasts. Does that help to do that kind of stuff to be able to get, because now you're known, is that more likely to get you more funding? Yeah, absolutely. And I thank you guys for giving me this platform, and with all the reach that you have, it helps tremendously. And all the different podcasts that we did, I think the first one goes way back to like Mercola, who's kind of controversial. And then people reached out were like, that's like the kiss of death. That's academic suicide game. I didn't even know who he was at the time when he contacted me years ago. I was like, yeah, sure, you want to hear. I was honored. I was like, yeah, you want me to talk about our research? So I did, and then my inbox exploded, and I didn't realize the reach he had. And then it was lots of people you guys know, Ben Greenfield and Tim Ferriss. And I think I did a little over a hundred podcasts at this point in Ted Talk. And that does give your research much more visibility, kind of puts the pressure on you too. And I think maybe that's the future of science. And scientists are kind of introverted in many ways, and will stay in their little silo shelter of a lab and just publish mechanistic papers on this particular kinase or phosphatase. And it doesn't really have a whole lot of relevance. But and Andrew, my student and I were talking about this, we're really lucky to be doing research that the public at least perceives as things that's very translatable. And when it comes to diet, there's like so much public interest in diet and people get very emotional about it. And it hits them like at the core. If you're promoting a diet because that empowers them, it's not some weird esoteric pathway that you can develop a drug for that they can't really relate to. I mean, this is like not just macronutrient ratios, but specific types of foods and supplements and things that they can use to empower themselves to treat a disease or enhance their performance or whatever. And that's pretty exciting, because I was in a pharmacology department. And when I started doing this high fat diet research, I saw some people like raising their eyebrows at me and just saying, you just entered a tenure track position and you're gonna get tenure trying to do research on a high fat diet. They thought it was like the academic kiss of death, academic suicide. But I kind of knew intuitively, if you're doing research that people are interested in and it serves the public in some way like the information and research you're putting out there, it's gonna come back to you. Like even if the government agencies are not funding this kind of research, like if you're putting out good stuff, like it's just gonna come back to you. You're gonna, we're gonna stay afloat one way or another. Dom, do you ever, do you ever have that fuck it? I just, instead of chasing all these grants and get, I mean, I feel like you got to connect a little bit with Navy SEALs, like all this hard behind the scenes work that nobody really glorifies at all. Nobody ever hears about or knows, right? Like, is there other, do you have moments in your career where you were like, you know what, I'm done, I'm gonna go make some money. And that's all, because a guy with your level of intelligence, I feel like could do almost anything here. Yeah, and make a ton of money. Do you battle with that ever? Well, also the thing that would make me markable or to make money is the science. So I'm really passionate about developing because I believe in what we're doing because we see it in the lab. And I feel like we're just at the cusp of this. And maybe if I was like, you know, in my, you know, 10 years from now, like in my mid 50s or something, and, you know, I would have a different perspective. But right now I feel like we put in so much time and effort just to get this thing rolling in many different directions. And, you know, we have students that are, you know, in the lab and things too, and they're working on projects. But I feel, you know, the science still needs to get out there. But when it comes to make it, yeah, a university setting can be very stifling. And in many ways, because there's a massive amount of paperwork, and I spend 70%, maybe 80% of my time just doing paperwork, writing grants and things like that, and not connecting with my students and not kind of in the trenches, you know, drawing blood or measuring this like in the lab where when you're a postdoc, I spent 90, you know, 5% of my time or 90% of my time just sitting at the bench like running experiments and doing like crazy kind of science stuff. And now it's just like a lot of paperwork because it's not just the science. And I got to do, you know, teaching and I got to do committee service and all those other stuff. Yeah. And that doesn't seem to be super conducive to the creative process, you know, to be in that environment. Well, I know, you know, different scientists like Otto Warburg or even like Hans Krebb, if you guys know the Krebb cycle, like they're in their institutions, they actually freed them up. Like in the old days, if you were kind of a productive scientist, they would pull all other obligations away from you and the university or institution would give you money and just kind of put you in the corner, like go do good stuff and report back to us. Be free. Yeah. Yeah. Be free. And that's awesome. That's like, that's a dream to ultimately. Nowadays, I guess if, you know, some donor, you know, donates and says, we really like what you're doing. And we think that, you know, maybe if we can give you some money, of course, you know, there would be like benchmarks, you know, and every quarter report back to us on your findings and that's understandable. And like the Department of Defense does that, you have to give like technical reports. Do they give you more freedom than the universities do? Yeah, they do. I would imagine because they're like, they're looking at the military and they're like, look, we need to figure this out now before, you know, I think you get more latitude, right? Yeah. There's, yeah, you, when you get funding from them, you have to write up technical reports. I think if it's, if you're DARPA funded, which is you got to do it like every month or like every quarter, but with the Department of Defense, like in, in May, I will go to the Office of Navy Research, undersea medicine annual review, where I got to step up on stage and present everything to the big wigs. And this is what I did this year. And, you know, these are the projects that I want to do and that sort of thing. And then it's kind of a conversation. So you don't not only submit technical reports, you have to kind of present your stuff to, to the organization. And that's, and that's, that's to be it, that keeps you on, that keeps you in line too, right? Because if you didn't have these benchmarks, then you wouldn't be, have something to strive for, and you could be steering off in this direction and that direction. So. Dom, do you feel like, because I got to imagine like, when you're doing this type of research, you've got to just be buried in it. You know, like you mentioned 16 hour days and just thinking about it probably nonstop. Like, do you find that you, do you have exercises that you do to kind of detach? Or do you have things that you're interested in that, that grab, that, you know, kind of help separate that part of your life for balance? I mean. Yeah. I mean, my wife makes sure of that, right? So, yeah, it's like, when I got married a year or so ago, it was like, you know, my weekends are for play for downtime and things like that, unless it's something, some big conference that, you know, I could bring her to. But we have dogs and every night we try to kind of take the dogs out and run with them. And I try to get to the gym for me. I like motorcycles. So, like the ultimate downtime for me is to kind of get home and get on my motorcycle and go to the gym and then listen to music and the combination of like music, motorcycles, gym, heavy weights, you know, meeting, talking, seeing some familiar faces and everything. That's like a huge dopamine kind of rush and dump. And it just gets me back. It kind of resets my whole physiology. And whatever is on my mind, I could have the worst day, like all day, but if I go to the gym and you have a productive workout, like everything changes, like everything's great. Oh, yeah, I think we can all connect with that for sure. But you seem like such a driven person that you probably just love what you're studying so much. If you don't check that, you'll just absorb yourself and everybody else disappears. And I think you guys can relate to that, too, because you guys love what you do and what you do is awesome. And I could like, I'm kind of really envious, you know, you're feeding off of all these people that you're bringing in and learning new things that you can apply to yourself and promote and disseminate the information out there. So, yeah, I mean, my students will tell you, and I have to kind of tell them, you know, to back off. I was like, you know, you guys are working a little too hard there. You got to take some time off and enjoy things. But as scientists, one of the benefits that we have is that we present at conferences all over the world. So we do have the opportunity to go and present at all, all these different places. And we always take a day or two out to do some sightseeing and have some fun doing that. But, you know, no matter how busy it gets, I always block out X amount of time, you know, at the least it would be 30 minutes, but usually more than that per day, just in downtime. You know, talking about your peers and doing that like, who are some of who your some are your favorite humans that you've met and that you've got to mingle with, besides us, or besides us, and research wise or whatever, like that you've came across. I mean, yeah, wow, there's so many of them that I consider like mentors and good friends now. Like, yeah, people that had really big info from my PhD advisor, who was pretty inspirational, Dr. Jay Dean, who basically developed this idea of doing science inside these hyperbaric chambers and building microscopes and electrophysiology equipment inside these hyperbaric chambers to stimulate and nobody else in the world was doing that. More recently, you know, I have a position at the Institute for Human and Machine Cognition, and that's run by Dr. Kent Ford, who he found me because he was actually doing the ketogenic diet for like a decade. And he was a former executive director person at NASA and developed his own Institute, which is really about building kind of humanoid robots, like the stuff like a Terminator type things. And he got, I think their Institute got second place in the DARPA Robotics Challenge. But his Institute is two things. It's human and machine cognition. So it's developing robotic, developing different artificial intelligence kind of projects and humanoid robots to basically understanding the science and the physiology of extreme environments. So it's part of it's like engineering artificial intelligence. And the other part is understanding the physiological limitations of these extreme environments and developing research programs to develop countermeasures, even ketones as a countermeasure to enhance performance in extreme environments. So a lot of it's NASA based things. And I've met, you know, some really fascinating people that I've worked with Kent, including Michael Gernhardt, who's been up on the space station many times and played a big role in doing the EVAs and developing various technologies that are up on the space station now. He's an astronaut. He was also with Ken, he was the principal investigator of the Lunar Rover, the Mars Rover project. And actually, when I was at NASA, Johnson Space Center, he gave me a complete tour of everything, including the Neutral Buoyancy Lab, where the mock-up of the space station is underwater. And he took me to the rover and let me drive it out on the lawn, you know, and doing like burnouts and stuff. That's awesome. That was really cool. Most expensive RC vehicle. Exactly. Figure eights. That's awesome. It was a pretty big vehicle. It's like, you know, we had three of us in there when we were driving it around. And it was one joystick. And it can spin on a dime. And it was really cool. So these are the kind of people that I never thought getting into this path of research would bring me in touch with these guys that are really icons in the field and icons and what they do. And they've been mentored to me in many ways. And working with the Institute for Human and Machine Cognition, my former, or a good friend of mine, Don Crenegas, who is also a full-time employee there, just served on the NASA NEMO-21 mission, which is an Earth-based base analog down in the Keys. And it's basically a laboratory underwater where you test out different technologies that are tracked for the International Space Station or Ryan, or basically what will be the mission to Mars. And so cool. And that's happening, right? I mean, didn't NASA just say like, we are going to go to Mars? Yeah. Yeah. So there's a lot of things that the public might not know about that need to be done in analogs here on Earth. And it's testing different technologies, whether it be testing different foods or different drills or basically a whole range of dozens of technologies was they were studied on the NASA NEMO-21 mission. And actually just recently, our lab has under the umbrella of IHMC will be contributing to the NASA NEMO-22 mission, which will test nutritional ketosis. And we'll look at things like body composition, heart rate variability. We'll look at gut microbiome. We're going to look at metabolomics, basically getting a snapshot of how our metabolism changes in that extreme environment and how ketones can help mitigate some of the effects. It looks like a lot of money is going into using ketogenic diet or ketones to mitigate potential damage, like acute or long-term type damage to the brain and the body. Extreme environments or oxygen, hyperoxygenation or too little oxygen or concussion or all these different scenarios where you can cause some serious damage to your body. It looks like there's a lot of money going into looking how ketones can help those situations. Is that am I being accurate? Yeah, absolutely. So it sounds- And even the heart too. So the heart is probably, I think there's more data for the cardioprotective properties of ketones for the heart than equally or maybe even more so than the brain. And early work was done in the lab of Richard Veach, who was a student of Hans Krebb in the Krepp cycle. And his lab demonstrated an energetic efficiency of ketones in the heart where you develop proportionally that the hydraulic efficiency of the heart was increased about 25% hydraulic efficiency of using ketones to burning ketones and burning glucose for fuel. So if I'm listening to this and I'm a listener, I'm thinking to myself like, okay, next time I go party for the next three days and I don't get any sleep and I'm gonna do all this crazy- I'm gonna eat a ketogenic diet to protect my brain from all this crazy stuff. Is that- that sounds like a crazy leap, but maybe not. I think the science is supporting that. So, you know- There you go, there's your advice. Next time you go to Vegas. Yeah, eat a ketogenic diet. We're gonna market that, bro. We're gonna sell that. I'll just say the Vegas trip. Party ketones. If you're gonna go party with hookers and poke, here's what you're just kidding. Yeah, maybe fasting too, so- Oh, don't eat, never mind. Or maybe what I like to call, I call it like ketogenic supplemented ketogenic intermittent fasting. Well, they both have a lot of similar benefits, right? When you carry them side by side, the ketogenic diet and intermittent fasting, I feel like that being said, we're all huge fans of- I mean, I typically intermittent fast at least once a week. I just kind of throw it in my routine. How often do you do it? I know you've- I know you did your study where you did, I think, what, five days and then you deadlifted like five hundred something pounds. I remember that. How often in your normal life, if you're not studying it, are you- Yeah, it varies, but typically once or twice a week with my normal routine, unless I'm like testing something. And sometimes it, like on my honeymoon, I think, where we went all through Southeast Asia, I felt it was probably best to do a little bit of fasting. I just came back from Thailand. I just came back from Thailand. It was bedridden with food born in West Java. Yeah, we went through like Philippines, Cambodia, Malaysia, all that. My wife's a crazy travel person. So yeah, so I fasted in some cases and brought some sardines on days that I- Oh, you still eat sardines for breakfast? I do, yeah. I do. All the smart people do, Adam? Not every day, but a lot of times when I'm traveling, we do. That's this guy over here for sure. What do you see now? Oh, we're selling this on the sardines. Where do you see with, you know, just to kind of, in the episode, I want people to kind of look forward, like where do you see future research on ketones? Like where should we point our gaze? Is it okay to make speculations on where you think they're going to start looking at, you know, how ketones can affect the body? Well, any research that's being done on metabolism I think is fair game for ketone research because ketones are an energy metabolite that's superior in many ways to other fuels that our body can use. So whether that be neuroscience, cardiovascular, oh, one of the papers that we got out in frontiers, neuroscience was the effect of ketones on anxiety behavior. So- Oh, that's a good one. Yeah, and we were gavaging or we were giving a dose of ketones to rats before we were diving them and observed that they were just easier to handle, easier to, you know, they're just calm, they're really chill. So we realized that we weren't anesthetizing them because when we put them on like a treadmill device, they can run equal or farther, you know, so it wasn't like they were sedating them. So it was actually my wife had the idea, well, let's get the equipment to do like an elevated plus maze and do these anxiety kind of measurements. And the data was really robust on that showing that it attenuates fear behavior. So with the type of experiment that we did, it's called an elevated plus maze, the rats can go into a little cave or they can come out like on a catwalk where they basically it's just like a platform where they could fall off the edge. They have to have, you know, an intuitive exploratory behavior and not be afraid of it. And there was much more time and you set up a camera to determine to calculate all the time they're in the open arm versus the little cave or closed arm and how many times they go in and out and all different ways to analyze it. But the bottom line was that the rats had a less fear response and more exploratory behavior when they were in a state of nutritional ketosis. And that has, we think implications, we just published that maybe a month or two ago. And it has direct implications, we think for guys with like PTSD or brain injury to where it can kind of contribute to like fear, but definitely PTSD. I want to see some studies with ADD and ADHD. Because I would assume, I mean, I'm assuming, but I would assume there would be some effect, you know, maybe a positive effect. I know anecdotally, I've have, I belong to fitness and nutrition forums and you got parents on there like, well, man, when I have my kids eat more fat and really restrict their carbohydrates. And I don't know if it's just because they're eating less sugar or whatever, but the ADD gets much better. Yeah. And I get a steady stream of parents that contact me that and they did, it's not even the key to it, just getting their kids off sugar and replacing carbohydrates with fat and protein. Don't say that to Lane. About the sugar. But yeah, Lane kind of has ADD too, I think. He's a denial. He'll tell you about it. He'll tell you about it. I'll let him tell you about it. But yeah, he, you know, and I think that can actually, if you can channel that into productive things, which I think Lane is an awesome, you know, example of that where he can channel emotions, he can channel ADHD and channel that into productive things that, you know, are helping people and that's, we have a lot to learn from that. So I think a lot of the high achievers out there, many of them are people that have, you know, ADD. The classic picture of like Einstein's desk and it's just covered in shit and it's super disorganized and you hear that a lot about, you know, smart people. So if, you know, I always say that when people talk about how messy my car is on the inside. Yeah. And he tried to simple, but like he didn't even wear socks because it was like another thing he had to think about. It's too much. That's just one too many things. Yeah. Well, excellent, man. It's great to have you on. Yeah, Dom. It's been awesome having you down here, man. Definitely. Listen, if you like Mind Pump, go to mindpumpmedia.com. We have 30 days of coaching for free. This is where we take all of our past episodes and we compile them into different topics. So someone topic may be fat, may be protein, may be wellness. You'll get an email with bullet points on that subject and links to episodes time-stamped so you can learn more about those particular subjects in detail. You can also find us on Instagram at Mind Pump Radio. You can find me at Mind Pump Sal, Adam at Mind Pump Adam, and Justin is at Mind Pump Justin. Thank you for listening to Mind Pump. If your goal is to build and shape your body, dramatically improve your health and energy, and maximize your overall performance, check out our discounted RGB Superbundle at mindpumpmedia.com. The RGB Superbundle includes maps anabolic, maps performance, and maps aesthetic. 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