Dominic D’Agostino, Ph.D., is a tenured Associate Professor at the University of South Florida (USF) Morsani College of Medicine in the Department of Molecular Pharmacology and Physiology. He teaches medical neuroscience, medical physiology, nutrition and neuropharmacology. He is also a research scientist at the Institute for Human and Machine Cognition (IHMC). His primary research focuses on developing and testing nutritional and metabolic-based therapies for a variety of disease states and advancing the use of these therapies into human clinical applications.
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AI Generated Transcript:
Cavin Balaster
Hey everybody welcome to the adventures in brain injury podcast. My name is Cavin Balaster. I’m the severe traumatic brain injury survivor given less than 10% chance of recovery beyond a persistent vegetative state, and today I’m super excited to be interviewing Dr. Dominic D’Agostino, Professor Dominic DIC, now, he is a tenured associate professor at the University of South Florida Morsani College of Medicine, and he’s in the Department of Pharmacology and physiology. He teaches medical neuroscience, medical physiology, nutrition, and neuropharmacology, which, as you all know, I’m extremely into all of those things. He is also a research scientist at the Institute of human and machine cognition, AI stuff. We can talk a little bit about that. And his primary research focuses on developing and testing nutritional and metabolic based therapies for a variety of disease states and events in the use of these therapies into human clinical applications. So excited to have you down. Yeah, it’s
Dom D’Agostino
been over like six months. Right?
Cavin Balaster
So I’m like that. Yeah, we met at the ancestral health symposium in LA. When was that last November?
Dom D’Agostino
I think it knows our time, wasn’t it? It feels like a month or two
Cavin Balaster
ago. You live in Florida. It always feels like summer, right? Yeah. Oh, was yes, it was it was summer. Man, it’s so good to have you on your I really appreciate your work and you’re a busy guy bunch, let me know some of the projects that you’re up to right now.
Dom D’Agostino
Well, I teach, my teaching is aligned with kind of like the research that we do. For example, I’m teaching medical neuroscience. So I teach about the action potentials, the membrane potential, the nursed equation, the golden AI, I teach it like how neurons maintain a membrane potential and communicate to one another and everything sort of involved in that and then signal transduction of neurons. And then neuropharmacology, I teach dopamine and physiology, I teach the whole gi section. So we can talk about the brain axis. So pretty much you know, kind of teach full time and get a lot of time is actually spent answering questions or preparing lectures and things like that. So I do that. But I also teach a lot of students in the lab, we have a good number of honours undergrad students that come under US masters students, PhD students, high school students, and we have postdocs, research assistant, you know, research professors, technicians working in the lab on a variety of projects. A lot of the work that we have done historically has been projects by the Office of Navy research, which is part of the Department of Defence. We have a nav see project and humans at Duke University looking at ketone metabolic therapy for preventing oxygen toxicity, seizures, and we did the sort of the animal model correlate of that in the lab. And that then set the way paved the way for the human studies. We have studies using continuous glucose monitors in patients and looking at CGM as a behavioural tool to improve everything from psychological measures to metabolic biomarkers, insulin, inflammatory markers, things like that things highly relevant to brain health. And then we have a lot of different projects on mouse models of like neuro metabolic disorders. So that could be glucose transporter, rare diseases like Kabuki syndrome, glycogen storage disease type two, for example, we had a project on Angelman syndrome. Each one of these projects sort of becomes a PhD dissertation. And we take a deep dive into the molecular mechanisms of these disorders. And even in the presence of a persistent molecular pathology, something like therapeutic ketosis, which is not well, we didn’t think it was actually changing the genetics, but it is changing the epigenetics. ketosis can help to manage and treat the disorder primarily looked at that by just its ability to provide ketones as an alternative energy substrate, but more recently, like one of my students is looking at the metabolic control of epigenetics. So how the ketone body beta hydroxy butyrate, for example, is activating, or reactivating genes that can be neuroprotective that play a role in learning and memory, synapse formation, things like that. That has become a big focus of our lab ketones as an energy source for one but also ketones as a signalling molecule. And a way to turn on genes through epigenetic mechanisms to help neurological disorders and actually enhance cognitive function behaviour.
Cavin Balaster
Nice, nice and I really love that it’s all about application. So for the listeners, I’m going to kind of break some of that down continuous glucose monitor that’s measuring your your glucose throughout the day like, yeah, it’s like a patch and it just lets you know where your glucose is at. And that’s really powerful because ketones glucose are both fuel sources or substrates. So when Dr. D’Agostino was talks about substrates
Dom D’Agostino
explained very nicely in your book here, which I recommend that people like that chapter you have in there,
Cavin Balaster
thank you, man. Yeah, so there’s substrates. And honestly, I kind of don’t like the term ketogenic diet, because it’s kind of like saying, the glucose diet. That being said, you know, whatever. And like, who says the glucose diet, right? It’s substrate. And so we’re talking about ketogenic metabolism, using that as a fuel source for our brains, has changes, positive changes in neurology, for many different aspects. And I want to talk with you about some specific things with that. I believe you’ve done research surrounding traumatic brain injury with mice in ketosis, is that correct?
Dom D’Agostino
Well, we had opportunities in the past, but my wife did not want to go down the path of doing a brain injury animal. So what we did we have models of brain injury without actually injuring the animal. So for example, we have neurons that are grown and then form a neural network in a dish. And then we simulate traumatic brain injury by basically cutting the brain in half or damaging the brain in a particular part. And then we can apply certain things to the neurons, we have artificial cerebrospinal fluid, which would mimic the brain. And then we can alter various components of the artificial cerebrospinal fluid. And if we keep everything equal, and then we raise the ketones up to like two milli molar, it enhances the formation of new synapses. So if you cut all the synapses, you create, like a physical line, and a damaged area, and then you can watch synapse formation. And then we can image that over time. And then we can also measure certain proteins like synapse and you know, BDNF and other things that are playing a role in enhancing that neuronal repair. So I mean, we do that. And then we have models of neurodegenerative diseases, you know, everything from Alzheimer’s, ALS to different model diseases. But we have never done sort of the messy work of actually being for
Cavin Balaster
hitting brain injury. Yeah. And animals. Yeah, that’s it. Yeah, we didn’t, it’s in gardening work.
Dom D’Agostino
I’ve applied for grants when I was younger, and I’m glad it didn’t get them because I’m not sure I could use this apparatus that just slams the animal’s head and recover the military. There’s a lot of research on that. And I think it’s, it can be very informative, not always predictive. I’m more into doing human or cell based assays and various things that could give us answers to questions without necessarily having to induce that kind of trauma. And all the disease models that we have the mice are bred up, and we do not hurt them in any way. But we let them kind of live their life. We have a longevity study. Now, the effects of the things like ketogenic diets or ketone supplements, on behaviour on learning and memory on motor function, and things like that. And these are fun experiments, because basically, the animal lives a certain age and you try to make the animal as healthy as possible and you enrich their environment to see how long they can live. We have some longevity studies going on now.
Cavin Balaster
Do you have to do that? I’m curious about you. You work with seizures as well? Yes.
Dom D’Agostino
Yeah, a number of different seizure types. Some of them are genetic, like seizure associated with like Angelman syndrome, or we have a model of absence seizures, which is having a seizure, but without the tonic clonic effects. So some people will have seizures that could be like, and they’ll just drop it called, like dropped seizures, or they’ll just be like staring in space, and their brain is actually having a seizure, but it’s not a grand mal seizure, also called a tonic clonic. So yeah, we’ve done a lot of research on an animal model of absence seizures, but the powerful tonic clonic seizures that we’ve studied with ketosis are CNS, oxygen toxicity, which manifests is very powerful. tonic clonic seizures and therapeutic ketosis. Well, fasting was shown to be helpful for that. And then we develop ketone metabolic therapy protocols. And then these are the protocols that we’ve vetted out and studied in animal models. And then we move them to human clinical trials, diets, and then you know, different agents that are being we don’t have the big human chambers and all that. But Duke University has a massive environmental research, you know, they contract out like NASA and DOD, they do a lot of research there. So we’re running some human trials and studies they’re
Cavin Balaster
not It’s nice. I mean, I’m so interested in ketones as metabolic therapy early in my brain injury. My mom, you know, when she rushed out to New York after I was in a coma, she began to read the literature and see that there was a metabolic cascade that occurs after brain injury, that often specifically diffuse axonal injuries, that often causes way more damage than the initial hit with a with a calcium cascade and things of that sort. And in my research, it’s like, I’m seeing that that sort of metabolic cascade seems to be dependent on glucose metabolism. And when when we bypass glucose metabolism, either through fasting or through ketogenic metabolism, which we’ll use that instead, it shows far better outcomes for the patients, the participants. Absolutely, yeah.
Dom D’Agostino
And it kind of falls in line with traumatic brain injury, if it’s severe. Or if it’s penetrating, for example, a penetrating traumatic brain injury, I think 80% of people will have seizures, where it goes through the skull. Yeah, we’re breaking the bone in the skull. So that kind of clarifies is a penetrating. And then in that context, I believe it’s upwards of 80% or more, we’ll have seizures. So it just made sense to me early on, like 18 years ago that the therapeutic ketosis has been a proven neuroprotective anti-seizure strategy for many years, even independent of like the genesis of the seizure, and temporal lobe epilepsy versus absence for glucose transporter Deficiency Syndrome. Yeah, across the board independent of the etiology. Therapeutic ketosis is neuroprotective and profoundly anti-seizure effects, you know, even above and beyond any anticonvulsant that we know. And it’s actually used when anti-epileptic drugs and multiple anti-epileptic drugs and high combinations fail. So in that case, only then do they actually pull the lever and use therapeutic ketosis. And in that context, about two-thirds of the patients respond pretty remarkably, I think a third have more than 90% seizure control. And like 10 to 15% are what’s called Super responders, which means they have complete seizure control. And then when they discontinued the diet, they never have seizures again. So this really interested me and the prototypical patient is Charlie Abrams. Foundation. So
Cavin Balaster
you brought that up, I was thinking all the time. So Jim
Dom D’Agostino
Abrams, was a Hollywood producer made the movie aeroplane actually collaboratively worked with Meryl Streep to do the movie first do no harm. And there’s a movie about the ketogenic diet called first do no harm by Meryl Streep. It was kind of cool. And then that drew me to this as you know, I majored in nutrition but it’s weird. I did not know if the ketogenic diet was a standard of care, medical therapy, and I was like, wow, I started learning more about it. I talked to people at Johns Hopkins and, and other Institute’s and I realised I reached out to Dr. John Rowe, who was at Barrow Neurological Institute at the time, and now he’s like, director and chief in San Diego, the neurology in San Diego, the hospital there. And he encouraged me to actually pursue this and I actually copy and pasted his email and sent it to my DoD programme manager. And they said, Okay, well, what Okay, write up a proposal. And long story short, it was funded, and it set us on the trajectory of looking at therapeutic ketosis for these powerful seizures. And then we’ve expanded the use of ketone metabolic therapy outside of seizures for things like cancer, things like ALS, and these rare genetic diseases that we’re studying that seem to be responsive. And I think traumatic brain injury is kind of like the low hanging fruit. It’s a messy area to research because the animal models are kind of stressful and to deal with animals that have traumatic brain injury, doing the actual traumatic brain injury is quite stressful, not only for the animal, but for the investigator. And we’ve gotten a lot of data from cell models, but people are looking for a drug. You know, the, the funding agencies that are finding the work are really mechanistically looking for a particular drug and particular pathway. And ketone metabolic therapy is player tropic, which means that there’s multiple mechanisms so likely working in synergy to enhance neuronal growth and repair and actually reduce the inflammation and associated cascade of events that result in neuronal injury. So much like the the anti epileptic effect Next, it’s not working through a mechanism of any known drugs because it works when drugs fail. So tends to work with many different mechanisms and synergy. The more I do this research, the more I realised that reducing neuro inflammation is a big part of it. Because, you know, PET scans show that when you have a seizure that increases inflammation in the brain. And throughout the years, people have contacted me that have, you know, disorders where, you know, they could have a viral injury, it could be something like herpes simplex virus could be Lyme disease, it could be other diseases that cause neuro inflammation and out of nowhere, they’ve had a seizure, and then they’ll start fasting and doing ketogenic diets, and then that’s controlled. So there’s no doubt in my mind that inflammation can is so important to manage that with traumatic brain injury. But I think it’s also part of the mechanism of the anti seizure effect of the ketogenic diet.
Cavin Balaster
Absolutely. Yeah. I mean, I work with clients. And you said that, they’ll use the ketogenic as like a last resort, higher safety profile than drugs, but, you know, then you get too into it. But clearly, they they’re going to fund drugs, which are patentable and ketogenic diet is not that enjoyable. Right. So that’s kind of the world we live in with this. But yeah, working with clients prophylactically, even, for example, I have a client who attends to have her seizures a week before she has her period. And so prophylactically we’ll use exogenous ketones around that time to prevent that sort of glucose metabolism. It’s interesting, she gets much less hungry Shi Jin, she doesn’t eat as much then and is bypassing that glucose metabolism, which seems to me is seizure activities dependent on glucose metabolism, much like the chemical cascade that occurs after brain injury, that I was talking about the end. That may be why we see so much neuro protection from ketogenic metabolism, or fasten like they mimic each other. Right. And it’s super powerful stuff. Yeah. So Charlie foundation is really cool. So Charlie Abrams, and if I remember, right, he no longer is on the ketogenic diet, and he’s fine.
Dom D’Agostino
Yeah, yeah, absolutely. Not everybody, I would consider Charlie Abrams, a super responder. And I’ve communicated with dozens of adult epilepsy patients over the years that actually got seizures as an adult. One of them is Mike dancer, and he’s in the UK. If you Google Mike dancer, epilepsy, you’ll find he’s got a very interesting story of being in fitness and bodybuilding and things like that. And he implemented the ketogenic diet, and it had a profound effect at controlling seizures, but he will have occasional breakthrough seizures, and he needs to maintain a ketogenic diet. And he has a modified version, a little bit higher protein, of course, it’s like very high and fish, and maybe some chicken, I don’t think he can eat beef. Actually, following taking many drugs over many years created a lot of autoimmune issues with his gut and things like that. So he had to, you know, so I think it helped repair his gut, it helped to balance out his brain energy and also the neurotransmitter systems. And it’s like, we connect, I connected with Mike, maybe 2008 ish or nine. And I recommended the diet, and then, you know, super busy and everything and months went by he was having seizures every day. It’s like, I haven’t had a seizure. And he had some help from Matthews friends, which is like a UK based Charlie Foundation, and they collaborate with Charlie Foundation. And kind of the rest is history. And it’s like the doctor basically said, Mike, you’re going to die if you don’t have brain surgery to remove part of the hippocampus. He took it upon himself because his doctors did not support the use of the ketogenic diet. They didn’t have the infrastructure really to medically manage patients at least where he was at and even a major city. So to many doctors, this is just it’s like a foreign language to them, like ketogenic diet. They don’t be the neurologist may know about it for paediatric epilepsy. But for adult epilepsy, actually, the work by Eric kossoff at Johns Hopkins was not published yet. I think that was in came in 2008 or nine, sort of the validation of the use of this approach for adult epilepsy. The paediatric epilepsy studies are already published. So Mike has had a very long road getting this and he inspired me to actually I put him in my TEDx talk, which was like 2012, I think. So I had to include Charlie Foundation, Mike dancer in my TEDx talk, because he was like, we were thinking about doing this in our research proposal and I recommended it to Mike. And he was like the guinea pig before I even started the studies in the lab. And it was like, Hey, go do this. I was like, wow, it does work. I just heard anecdotally and just a few reports online at the time, but Mike kind of validated it because I knew his situation was the worst of the worst. And I was like, Okay, I believe this is going to work in adults. Let’s develop this as a mitigation strategy for Navy SEALs. Working with the Navy, we had a workshop and my programme manager was like, Man, this looks very compelling. Like, so I gotta be grant. And that helped us fund a lot of our studies kick kick us off.
Cavin Balaster
Awesome. So cool. And yeah. It’s interesting that it’s kind of a last resort. I mean, there’s some doctors are like, yeah, you could do a ketogenic diet, but that’s dangerous. Right? Yeah. Is it dangerous? Or the drugs with like, a page of side effects? Are those safe, like, dying like you did like what? Acetone in my breath or something like that, like, it’s not a big deal.
Dom D’Agostino
With drugs, you’re looking at long term side effects, especially when it comes to kids. Something like there’s a lot of drugs that have been used to control like infantile seizures, and like Status Epilepticus. And these drugs, when given just several times, can cause a delay in development that ultimately impairs IQ and just overall development. And, and that can be really sad situation when when kids are put on these these kinds of drugs. I mean, Charlie was put on a lot, a lot of drugs. And then that’s why his father became very angry that this option was not offered to him. That’s essentially why he made the movie first do no harm just because you get more exposure for this because he didn’t know it wasn’t I mean, he has, you know, being at the position that he was at, and the resources that he had, and he had to fly all over and basically go to Johns Hopkins from California. Yeah. And to doctors there. I mean, it wasn’t even offered, it wasn’t even an option. And he had the best options, you know, where he lived at the time, I think.
Cavin Balaster
And not to mention the kidney and liver damage that drugs are doing as well, because your your kidney and liver have to do a lot of work to detox that stuff. Yeah, the way I’ve steered my recovery is pretty simple. I went to a restaurant and unknowns against the degree and possibility of potential benefit, right? And see what the deal is with us. So when it comes to drugs, we don’t know what the facts are, or we do know the facts like all right, that’s some definite risks weighed against the benefits, okay? It can prevent, but then also, we’re damaging the kidneys, the liver, like all these things down the line. And then it’s like, Okay, how about exogenous ketones? What are those? You? Right? Yes, there’s unknowns. But so far, so good. And the degree and potential benefits is huge. I have an article about keto on my website, feed brand.com, forward slash keto. And then of course, you’ve done enormous amount of work in this department. And if you want to get exogenous ketones, you can get them there as well. You have exogenous ketones, or your wife does or something.
Dom D’Agostino
Yeah, well, I don’t have a company. But you know, in the process of doing this, it’s like most of our work published work has been with ketone esters. And I think they have tremendous applications for like maybe acutely for military operations and things like that, although we observe that with long term studies with the ketones and we look at the liver, so if you take a ketone Ester, like one three butane dial, and then there’s one three butane dial, which is ketogenic, it’s being sold as a ketone Ester, it’s really not. But if you want three butane dial, beta hydroxy butyrate. Mono ester is one Ester, there’s one three butane dial acetyl acetate, diaster. And there’s different with these ketones. A lot of our research is based on them. And they’re, they’re very efficacious, acutely, but I it’s not something that I would like I have them all over the house. And in the lab, it’s not something that I would want to take like on a daily basis, but it also tastes pretty bad. And they’re also they can be kind of expensive. They’re more like a drug. So that’s like the ketone in a drug because your liver once would be 18 dials and alcohol or to die all at the glycol which is a dial or die alcohol, and it has to go through that liver pathway. So when we give the animals that we, in the beginning, we were killing animals, we were putting them into ketoacidosis and we had to back off on the dose and figure out okay, they’re metabolising it but it has very powerful effects at elevating ketones and preventing some of the seizures. But we do notice, you know, I didn’t talk about as much maybe as I should have an early on, that there was some liver damage. is your evidence of liver damage? And it’s like, okay, well, the one $3 billion needs to be metabolised. And that’s why we’re seeing the liver enzymes go up and then you see like, a lot of red blood cells in the liver. And then over time, like evidence can start to happen have necrotic effects in the liver, but that’s actually giving them like every day like you and but a lot of people like I take ketones every day, but I take ketone salts supplement, I have it here, the Keto start product is what I used. We took the ketones that we use in the lab, like I told you about the traumatic brain injury thing where we do. There’s also an area of ketones that are not ketone esters, and they’re called ketone salts. So you take beta hydroxy, butyrate, and then ionically. bind it to sodium, potassium, magnesium, for example. And when you consume it, it liberates to ketones and then the electrolytes. So it’s like an electrolyte supplement that delivers the ketone. So your ketones go up, you replenish electrolytes, which tend to be a little bit low. If you’re on like a lower carb diet. These are what I use, I only actually use one packet a day, I do like a quarter of a packet with creatine, to creatine monohydrate. You don’t have to buy all these fancy Koreans, the generic creatine monohydrate is plenty good enough. You know, I mix that it’s like one of the first things I take in the morning, zero carbs, just ketones creatine, get your brain firing, go do some work, start brewing some coffee that hour or two later, I’ll sip on coffee, but then I’ll take the rest of the packet and mix it with another, you know, two, three grammes of creatine. And I’ll take that before I work out. It’s like my pre workout. Real simple, I only take maybe, you know, sometimes no supplements but because my diets pretty good, but usually ketones and then maybe like six supplements total, like magnesium three and eight is very good. And alpha lipoic acid, I think are two supplements that I use which would apply for brain injury Alpha Lipoic Acid can help you overcome impaired glucose metabolism in the brain. So that can be helpful is part of the pyruvate dehydrogenase complex. And then magnesium can help to damp in excess glutamatergic hyper excitability by attenuating, the NMDA receptor activity, which if you have a lot of glutamate in the brain being released, not only like right after the injury, but significant amount of time after. And even if you’re like certain disorders and certain even if you have infections, you can have excess glutamate and when people have headaches when people are just anxious is probably too much glutamate. Magnesium can have a nice calming effect. Actually another supplement that I take his melatonin, and I take that every night, I did research and I published it in Journal of Neurophysiology to show that it’s very protective to the hippocampus, and preventing oxidative stress and damage to actually put a lot of time and effort on antioxidants to prevent oxygen toxicity seizures, and they I got nice data but like the melatonin did not have anti seizure effects, although it like helped. It was neuroprotective, but it wasn’t it didn’t have anti seizure. So I kept searching and searching and then I stumbled upon I started the melatonin and stuff and like 2003 or four, I’m convinced that someone with brain injury you should be taking it at nighttime as a supplement and maybe even higher doses, maybe even like 510 Even 30 milligrammes some patients I’ve communicated with really high, it’s permeable to the brain, it has protective functions. So that’s my short list of supplement, I’m not a big supplement guy or food guy. Well, the ketones are helpful too, because not everybody’s gonna like, really dial back those carbs, to put them into ketosis. So you could do a low carb diet, and you’re getting the benefits of low carb diet, but you’re not in ketosis. So So adding like MCT oil, which is great. And then some exogenous ketones on top of that is like the direction that I would recommend,
Cavin Balaster
and that’s the exogenous ketones salts. I’ve found that that ketone salts while while transitioning into a ketogenic diet makes it a lot easier. Because you know, your liver needs to figure out alright, I need to take this fat and turn it into BHB beta hydroxybutyrate or ketone bodies, right? livers not used to doing that first. So it’s like, wait, what’s going on here? Right, um, insatiable carb cravings, right. So ketones exogenous ketones really, like, calm that down. And you know, you’re talking about melatonin and these super high doses. I’ve been reading up on that, a bit upwards of like 50 grammes or more a night when 50 milligrammes where, you know, typically you got a supplement that’s like one diag high dose is considered four milligrammes. But again, it’s the safety profile of melatonin definitely can get you feeling very groggy, but a powerful supplement for the brain, and for all sorts of things with the antioxidant aspects of it. But I have a seizure,
Dom D’Agostino
not anti seizure, but it protects the mitochondria. And I’ve been in correspondence with people that are taking gramme amounts of melatonin. And my first question is like, what does that make you feel like during the day because your body secretes? So you’re totally overriding that. I take melatonin not for sleep, I sleep fine. But I take melatonin as preventative. I mean, it’s preventative for Alzheimer’s disease, a preventative for oxidative stress, and it has just so many benefits. Some may argue and I think Andrew Huber Minh has talked about this in a podcast before which made me go search the data that it could have a suppressing effect on the hypothalamus and actually like your testosterone, and again, that atropine releasing more. But if you go to the data, there’s no human data to support that some data in animal models. I’ve been taking like high doses since I was like a teenager, pretty much. I’ve always had blood work and everything has been fine. So I think your body kind of overrides that, but there’s no doubt that Melatonin is a hormone, and it does have other effects outside of circadian rhythms. But the point I wanted to make is that I’m in correspondence with people who took gramme amounts of it, and they actually feel better during the day like actually it makes them feel better during the day, and it does not make them groggy. I felt that if I take a larger dose of melatonin, I do get a little bit groggy in the morning and maybe want that caffeine a little bit more. I think that taking three to five milligrammes of melatonin is probably saturating your melatonin receptors in regards to sleep, and wakefulness and things like that. But when you go up into the really high levels, you’re not augmenting the sleepiness anymore. But then you’re getting into situations where the concentrations reaching the mitochondria and having more of a mitochondrial metabolic effect. And I think I’d like to revisit and go back. It’s literally been two decades since I’ve been handed the melatonin research, but I’d like to go back and revisit and study that for other neurodegenerative diseases.
Cavin Balaster
And you know, a lot of people are afraid of a negative feedback loop on that, you know, where basically your receptors become less sensitive to it, or your body’s endogenous or your body’s ability to make melatonin is turned down or something. But that’s not the case, is
Dom D’Agostino
it? No, it doesn’t seem and like sometimes I will run out, and I just forget to buy it on Amazon. And then it’s like, you know, I’ll or I’m travelling I forget to bring it with me. Although when I cross time zones, I usually pretty I have like an international travel bag, and like a domestic travel habit, I keep it in my international travel bag for you know the purposes. But if I forget to take it, which I often do, it didn’t seem to affect my sleep latency or ability to fall asleep or stay asleep. So I weaned off of it. And then I went and actually did bloodwork to look at my melatonin and it was like, nicely in the normal range. So and that’s after taking it for literally 30 years. So I don’t have any beer, at least in my I mean, everybody’s different, but I’m just getting my
Cavin Balaster
Yeah, I have similar experience. Yeah, I, I actually get a bit groggy. If I go from like zero to 100, you know, ramp up, then my body’s better at handling it. But yeah, I get groggy in the morning with a visit to higher doses. And my understanding is that our cortisol is converted into melatonin. So as long as we’re producing cortisol, which we do, we’re producing melatonin, so it’s converted no matter what, which is why this negative feedback loop doesn’t occur. But anyways, this is totally tangential. I wanted to talk with you about ketones we’re on we’re on melatonin now. Which is totally cool.
Dom D’Agostino
Yeah, I think it’s of interest to your audience, like visited the melatonin Wikipedia page, but I just I studied this when I was younger, and there’s quite a lot of data behind it. So and I think it’s being used for a variety of other things. You know, it didn’t pan out for us to use it for oxygen toxicity. It had neuroprotective effects, but didn’t have anti seizure effects. So the ketones hit both categories, right? They have really strong anti seizure effects. And they also have pretty remarkable neuroprotective effects. So that’s why I kind of put on, you know, switch all my time and effort actually from drugs to studying ketones, exogenous ketones. Thank you Janka. We study exogenous ketones time restricted feeding, and then all the different variations of the exogenous ketones to and I think there’s different formulations. I also like to add that MCT oil is quite interesting. And then if we add MCT oil to ketone salts, or if we add MCT oil to ketone esters, then we always got better effects. So the MCT is like, it basically causes your own body to make its own ketones. The hmcts, through beta oxidation of fats help you produce your own ketones, while it delays gastric absorption and helps to promote a better what we call a pharmacokinetic profile of the exogenous ketones. So it’s like, you know, you take an MCT exogenous ketone mixture, and the ketones go up and down and it shifts the pharmacokinetic curve to the right. But the area under the curve is of ketones is quite higher. If we’re measuring ketones, it’s more than like an additive effect. So you can get higher levels of ketones. If we combine MCT and exogenous ketones, and either one alone, and then there seems to be like a synergistic effect too. And I think that has to do with some dynamics we’re trying to understand in the lab, so we have to do liver metabolomics to really start understanding some of this, which we’re starting to do now.
Cavin Balaster
That’s awesome kind of speculation, but like, we kind of jumpstart our liver with like some exogenous ketones like, Oh, you want me to make those? Oh, my God gave me the substrate. Cool. Yeah. You know, maybe that’s why it’s happening. I don’t know. But yeah, very cool. I was curious because something I’ve experienced with exogenous ketones, is sometimes I ran by exogenous ketones, I mean, ketone salts, usually with the MCT in there as well. But I have, I tend to have just gut upset like digestive problems with that, what’s your experience and thoughts surrounding that.
Dom D’Agostino
So actually, that inspired the formation of a ketone salt, balanced electrolyte formula that inspired like the development and testing of keto start. So pretty much all other ketone salts on the market, especially if I take the ketone salts on an empty stomach, send me to the bathroom. They are fantastic laxatives, but you’re basically literally flushing the ketones and the electrolytes down the toilet. So you need to have a pretty unique electrolyte blend to get maximum ketone absorption. And then some of the other things that people put in like a retro tal or other sweeteners and things like that. can upset or irritate the GI system, the electrolyte blend that seemed to really maximise ketone absorption was, interestingly like the same ratios of salts that the supplement element has lm n t. You know, Rob
Cavin Balaster
off company?
Dom D’Agostino
Yeah, yeah. So and I guess it’s probably not coincidence, right? Because we, I mean, we tested everything and it was like this formulation seems to just like totally optimise absorption and reduce gut and it’s like, when you look at the numbers, it’s like, man, maybe Rob, Rob knew the correct electrolytes formulations for absorption. Those electrolytes are bound to, I forget what they’re bound to, but in like keto start, they’re bound to the ketones, right? So you’re delivering electrolytes. I still use elements actually, I’ll do keto star, pinch of elements because pretty strong and then put some creatine in there. Five grammes of creatine with water on empty stomach is a gut irritant for me. So that’s why I break it up into two or three gramme dose, you know, two or three grammes in the morning and then two or three grammes in the afternoon and I buy a quality supplement, I think, optimum nutrition or something like that. There’s more research on creatine monohydrate and more studies than any other nutritional supplements on the market, like easily. So, if that’s something your viewers or followers are not using, yeah, definitely. Creatine is definitely shouldn’t be on the list of very important for people that are not eating a lot of meat. But even if you’re eating a lot of steak and meat, you could probably top off your creatine levels with creatine monohydrate two grammes a day three grammes a day something like that, and I don’t think we need to cycle it either. But it does seem to synergize well, with exogenous ketones, so you got the ketone energy, you got the creatine energy, then you got the electrolytes which basically enhance absorption, maybe expand your blood volume a little bit for when you’re working out, and that can be beneficial.
Cavin Balaster
Yeah, yeah. I remember high school getting all swore with creatine, and then like you No, but it was like, not really strong, but definitely likes role. But then after brain injury, seeing the positive effects neurologically, and whatnot of having cretin involved, is a really good thing to stack up there. But, you know, I really liked what you said about nutrition first. And that’s absolutely in line with data in my book. It’s like, we didn’t evolve eating isolated nutrients in pill form. We evolved eating food, animals, plants, things that are available to us. Our food wasn’t created in a lab, right? That being said, for example, MCT oils, where can we find those in the food supply?
Dom D’Agostino
So MC teas would be a bit difficult to get coconuts, right. So there’s palm kernel oil or palm oil, but then coconut? I don’t know if you had Mary Newport on but she agreed. Yeah, I agree. She’s like the leading expert on this. I helped write the foreword to her book with my previous PhD student Mallette. Dr. Millennium bromo Yeah, it’d be hard to get a good quality coconut oil, I’d recommend getting it and then Coconut oil also has other oils that are beneficial, like lauric acid, for example. And lauric acid can have antiviral effects. Viruses are neurotoxic. CMV, Epstein Barr Virus, herpes simplex virus, the lauric acid can coat the virus and kind of render it relatively inactive. So theory at least. So there’s that and then yeah, I’m all about food sources. You know, the big one is fish oil, especially for brain injury. So my wife just did the Omega quant test and had about a third of the amount of DHA and EPA that I have. We do eat I mean, we go out and eat salmon once a week or so. But we’ll cook it at home but I like I have sardines in my bag here. Right. So I eat fish, pretty mackerel, sardines. I’m a huge believer that a lot of the benefits a lot of the research on fish oil are just by eating fish. Right. So if you can eat fish, and I was not taking a fish supplement and just eating fish, and when I got my levels checked, I mean, they were like off the charts, Omega three very low Omega six. But my wife, on the other hand does not like fish enough to eat as much as I eat and would have to supplement it. So you gotta be careful like Nordic Naturals there. They’ve been around since the 1980s. They have like a super legit Nordic Naturals, good fish supplement a few others, but I’m usually hesitant to recommend it. I don’t purposely don’t supplement visuals because I think it’s important to get it from fish. Some people will not eat fish.
Cavin Balaster
Right, exactly. I have a fish oil supplement that’s really powerful is DHA, concentrated, mono glyceride. So, triglyceride is considered better than ethyl Ester form. monoglyceride is what our body does break triglycerides into mono glycerides, they can go directly into the cells. On top of that it also emulsifies the fats that are in your foods like acts kind of like bio alomost and most most vice baths for absorption. So it’s really powerful. But you can also go to iFocus IFO s, international fish oil standards, I think. Yeah, yeah. Yeah. And they they rank all these supplements and they’ll, they’ll get you they’ll they ensure it’s a good fish oil. Because if you’re eating rancid fish oils, you’re not doing your body any good. Who knows? Yeah, yeah. Be Wild West and supplement world of like, you don’t know where what’s coming from whatever. And I’m really glad that we’ve come together and developed some standards and found some ways of getting really high quality products to people. Because so important,
Dom D’Agostino
guilty of that, you know, I was just gonna I bought like a bunch of fish oil for my dogs because you didn’t want to go, like the expensive route. You know, Nordic Naturals. They’re kinda pricey. But I think they have a dog supplement, too. But I mean, that’s what I would use if given the option. I mean, there’s a couple other good companies to have any association with Nordic Naturals. But, you know, I bought some stuff for the dogs, and I opened the bag officials and it was like It smelled like fish. It smelled fishy. And that’s the telltale sign that these officials are oxidising that they give off volatile organic compounds that are indicative of oxidation and once you start chain of fatty acid oxidation. It’s like a feed forward process, then it’s like it becomes exponentially higher over time. So yeah, just something to consider when you’re buying fish. When you’re picking official supplement. Yeah, go to that website, choose reputable brands, the company should have been around for more than ideally like two decades. So pick your and pick your companies selectively I guess.
Cavin Balaster
Totally. What are you up to these days? Like, is there anything you want to announce to the audience? about what’s going on?
Dom D’Agostino
Yeah, thanks for asking. Well, I maintain the website, keto nutrition dot o RG. So we have different writers on there. We have blog topics on a variety of different topics. And I think we should do a designated one on traumatic brain injury. We’d love to work with you on that we have guest writers. So keto nutrition.org, where I put a lot of time and effort on outreach stuff. I’m on a variety of podcasts. So sign up for the newsletter. And the newsletter will basically is the different products that I’m testing self experiments, and I’m doing podcasts and I’m on when this podcast come out, I’ll put out a newsletter, blast it out to our our subscribers. And then I’m a co host for the metabolic health summit, with Dr. Angela Poff, my former PhD student now research associate and Victoria field, who is a fitness professional but also prior NEWS CASTER think NBC and also an expert in nutrition and working with patients and things like that. The three of us hosts metabolic health summit, but we also started a podcast called the metabolic link. And you probably never heard of it, because just launched and we just got a couple episodes out. As mentioned, we’d love to have you on. So I’ve been, you know, dividing my time between full time teaching full time research, and then educational outreach, which is really tied with the research and teaching that I do on neuroscience and physiology, nutrition very much into fitness and working out because I think there’s a synergy, also a synergy when it comes to brain injury that you have nutrition and exercise. One and one does not make two in this regard. I think the two are synergistic. So one in one equals three, I think the benefits of exercise can augment nutrition and vice versa. I’d like to steer our research into like objectively analyse, it’s a therapy, you kind of have to study that therapy in isolation, right. But I’m very interested now in formulating and putting certain diets and supplements together. And then testing that but then adding different types of exercise to help enhance muscle retention as it pertains to longevity, cognitive ability, inflammatory biomarkers, and animal models, testing it there and then moving the science to human application. I think that’s the theme of our website, like moving the science to human application. And that’s what really got me interested in doing more outreach, because the stuff that we’re studying in the lab has direct and immediate translatability. And that’s why it’s kind of fun to talk about.
Cavin Balaster
That’s perfect. Yeah, science to the void. Is it from theory to practice? That’s, yeah. Keith Norris from paleo effects, who’s just family to me. And yeah, he’s always said, from theory to practice. And I really love that my first presentation, my first keynote presentation, after my brain injury was called synergistic therapies. How therapy’s done together are more powerful than done on their own. And when it comes to research what you’re saying with these isolated variables, I’m recovering, I’m not isolating variables, I’m not going to find out like, Okay, I’m not going to do anything but this one therapy and see what happens right now. No, there is a synergistic effect that happens with all the stuff so I was, you know, doing neuro optometry and functional neurology and nutrition and ketosis and bringing all these different aspects in order to heal myself. Breathing this like stack to be researched, is really cool idea. So in my training in functional nutrition, there wasn’t so much protocols, but more systems of how we can find what the protocol should be for this individual. And I would love to personalised Yeah. Implement, personalised, like building systems and having those systems be tested rather than here’s the single drug that is the magic bullet and digital is going to work for everybody. Yeah, it never works, right. Yeah. So,
Dom D’Agostino
you know, it’s not I mean, nutrition is a big powerful lever, and then a supplement. So like a little letter, right, but I think bigger letters to our nutrition ties into this too is sleep, and sleep in general and stress reduction. So sleep stress reduction, and probably one of the biggest hacks, not for everybody is actually to have a pet like a dog. For us. Dogs are a form of therapy. It’s like canine therapy, there’s a farm right by us called Equine Assisted psychotherapy. I meant to go in there and check them out. And we have cows, and we have sheep. And we’re fostering puppies. And we’re looking for forever homes for our puppies. A pet, like a dog is on a schedule, we’ve got to walk them day and night. So after our breakfast, and after our dinner, we walk them and keeps us in shape. And we’re attentive to them and they eat what we eat, they have the same diet as their microbiome, they keep us active. Actually, there’s just amazing amount of things that they do to your body, like increase oxytocin, you know, they get you moving, they just, and the relationship that you have with them. So it’s pretty big, a big component of our life. And it’s probably one of the biggest hacks. So there’s like sleep stress reduction hats, but also cognitive engagement. With synergize, that could be learning language, it could be playing an instrument. My wife really wants me to go dancing with her on the weekends, as she does dance classes, and which is great because you have physical, cognitive and social like synergistically combined. And all the top longevity researchers are adding now that dancing is like the major hack. Maybe I should do it. But I think there’s a lot of opportunity for people to in when it comes to brain repair, from traumatic brain injury, to leverage nutrition, supplements, exercise, sleep, wearing a device to track your sleep, because sometimes some of the things that disrupt your sleep are not always obvious. I mean, you could get I have a Fitbit Charge here. It’s like 120 bucks, but now you can get it for like 40 bucks, 50 bucks. And then you know, give you good information on your sleep. pricier ones who will give you fairly good HRV data, not that pricey maybe like 120 bucks, get a Fitbit Charge or something like that. Or rank two, which I use. Yeah, super
Cavin Balaster
use bio strap not wearing the right. Oh, yeah, those are good. Yeah, yeah. Excellent. Yeah, man, we have more in common than you even know. I have a dog. He’s 1516 months old now. He’s been like, he’s, he’s occupied a lot of my life for some time now. Because I just, I love him. And I’ve trained a few dogs, trained to be service dogs. And he’s phenomenal. I love training animals. It’s like, something that’s so good for me cognitively. And for connection. I mean, and when I’m training a dog, it’s like, I’m not trying to get them to obey me. I’m trying to build a synergistic or symbiotic relationship. He wants to please me, and I want to hang out with them. Right. And like, it’s like, it’s all over that. So and I feed him raw meat. For the most part, you know, it’ll be raw labour.
Dom D’Agostino
And yeah, and sometimes we have like canned macro because it’s pretty cheap. So and I eat it too. So I’ll get a canned mackerel raw egg yolks. Liver raw me can macro. We also use a pet we use a it’s freeze dried, I think of visionary, visionary pet food, which is like a little bit pricey, but it’s like very low carb ketogenic, top end. And so we’ll kind of mix that in with it, too, especially if we have like a, because not everybody, like sitting your dogs or taking care of your dogs wants to like, do the raw meat liver kind of thing too. So we’ll use that. We give them a little bit of that each day. But yeah, pet nutrition. That’s a whole nother topic.
Cavin Balaster
I would love to also man, it’s such a pleasure to be spending some time with you and chatting. You know, I’m in Sarasota right now. Yeah, we’re like an hour north or something like that. And we got to come over
Dom D’Agostino
to our farm and see the lab and yeah.
Cavin Balaster
Yeah, yeah, like what’s happening? You also do stuff in the lab. Tell me about what kind of things you got going on in the lab. I would love to see that while I’m out there.
Dom D’Agostino
Yeah, getting you inside the facility is sort of like there’s like security and kind of to get into where we actually housed the animals, but we do some very cool experiments on behaviour where we look at like cognitive function, my student developed in olfactory learning test, where we couple certain sense to certain cognitive tasks and behaviour to basically look at learning and memory within without ketones. So we have that going on, we have animal models of different neurological disorders that we’re studying. And we have these hyperbaric chambers, where we put in animals and then we pressurise it, push them to having a seizure. Right, it sounds kind of cruel, but it’s quickly reversible. And we’re doing the same thing in humans. So we have volunteers that come up, and we actually push them to seizure, but we’re doing that at Duke University. So it’s no different than what we’re doing to our humans. And it has to pass you know, an IRB. And we do that we developed a ketone metabolic therapy. In the animals, we have a biosensor that looks at diaphragmatic, EMG, EEG, body temperature, we have a lot of different metrics coming from the animal. And we also have cameras set up to look at behavioural seizures. And so the idea is basically to really develop a protocol to detect an incoming seizure, and then to decrease that. So we’ve been able to essentially create super rats. Some of the things that we’ve tested are ketone esters, which are very powerful. So we have to gently apply these things to humans, because they have the potential to do harm. If we do the dose is too high. So that’s again, why I personally use the ketone salts because I’m getting the benefits and they taste good. I’ll have to say that if I was forced to do a dive outside of the dive tables, and to be you know, using a high pressure oxygen at very high depths, I would probably want to dose myself with a ketone ester and not salt. But pretty much every other scenario, I would rather do like a ketone, electrolyte salt, for me, so we’re doing that. We have cancer studies that we’re doing. And then we have cell based studies that we’re doing in the lab. We have a hyperbaric Biomedical Research Lab, we have a metabolic medicine lab. And then we have an animal facility where we do like a lot of our behavioural
Cavin Balaster
experiments and stuff. Oh, man, I’m so glad I asked about this. That’s amazing. Yeah. And are you a diver?
Dom D’Agostino
Oh, yeah, yeah, I sent a recreational diver since college. And then I did a more advanced training and then ultimately training to do what’s called saturation diving. I was on NASA’s extreme environment, mission operations, and I trained with astronauts, shell Ling grin, Samantha Cristoforetti. Jessica Watkins, who were just up on Space Station, SpaceX crew four, and we went over to Kennedy and watch them launch. We met them before but we lived with them like I lived with Shell in the habitat. He was like the bunk right below me. And we lived with him for 10 days. We trained with him at NASA. And then we lived in a hyperbaric environment where we I stayed in ketosis we did we were the aura rings with polar v 100. collected a lot of data, some of it, we published a lot of it, we still have to publish. I was on Nemo 22. And my wife was, she’s a more experienced diver actually chilla she was on Nemo 23, which is all female mission. So yeah, we have saturation diving under our belts, we have some NASA analogue training under our belts. And then we were PI’s on like, you know, five or six IRB protocols to do research on that. So and that’s kind of separate from research that we did at USF. I had to take vacation time stuff to do that. But it was super fun. And it was super intense. And I learned a lot and made some great friends with very cool people at NASA and with astronauts and also the team at NASA that runs that and Mission Control. Just amazing people in NASA just like so professional to work with. And it was probably one of the best experiences of my life. Living underwater for 10 days. It was very fun.
Cavin Balaster
Wow, you’re so cool, though. I’m
Dom D’Agostino
very thankful to be able to. I mean, I had a love of diving, but to actually be doing research on diving, and it’s just yeah, I have to pinch myself
Cavin Balaster
sometimes. Yeah, I’m learning how to dive right now.
Dom D’Agostino
So Oh, fantastic. Yeah,
Cavin Balaster
I’m excited for it. I’m excited. Yeah, man. Yeah. All right. Well, when I’m out there, I’d love to see this, some of the work you’re doing and all this. And yeah, let’s figure out when we can make that happen and gather to stuff and makes more magic happen.
Dom D’Agostino
100% I’m all for it. Yeah, let’s get to my calendar. I’ll send you some dates and times and things that would work and be great too. I mean, maybe come visit the house too. And We have a big pond go diving in the pond I’ve never done that but women if it happened went like scuba diving there there’s alligators in there but uh yeah let’s let’s make it happen
Cavin Balaster
sounds adventurous All right my friend. Until next time the y’all and we’ll see you next time thank you.
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