Ketosis is often reduced to a diet label. In Dr. Dominic D'Agostino's work, it becomes something more precise: a metabolic state that changes how the brain uses fuel, how inflammation (discussed further here) is managed, and how the body responds under pressure.
This is the full transcript for Scientific ketone protocols for longevity and brain health | Dr. Dominic D'Agostino.
What do you think are the best supplements to take for brain energy and energy levels and mental performance? I like magnesium uh glycinate, MCT, creatine, monohydrate, BL beta hydroxybutyrate, 10 g of BHB, melatonin occasionally. What what dose melatonin do you use? So what are the five to 10 benefits of being in a state of metabolic ketosis? Uh neurop protection and general brain energy stability. Also, it reduces systemic inflammation and neuroinflammation. It reduces insulin and that increases fat oxidation, helps sort of train your metabolism to burn fat more efficiently, enhances mitochondrial function. They have more mitochondria, more efficient mitochondria. And then there's like epigenetic effects that we can go into things on like visceral atapose tissue. Probably mentioned more than five there. So, do you think ketones or ketogenic diet and longevity can go hand in hand? Dr. Dominic de Agostino, welcome back to the podcast. Great to be back on again. Thank you for having me. Hi everyone. Today we have the privilege to learn from Dr. Dominic Aostino. He is one of the leading voices in metabolic health. He's a tenur associate professor at the University of South Florida Morsani College of Medicine and a senior research scientist at the Institute for Human and Machine Cognition. His lab pioneers metabolic therapies including the ketogenic diet, ketones, and hyperbaric oxygen. And together with his team and his colleagues, he applies these therapies to some of the hardest problems in medicine, epilepsy, neurodeenerative diseases, human performance, and even cancer. His work has taken him from NASA missions to Navy Seal research, studying how the brain performs under extreme stress. He earned his PhD in neuroscience, holds multiple
his PhD in neuroscience, holds multiple patents, has published in peer-reviewed journals, including top journals like cell metabolism and nature medicine. So, a few people understand human metabolism and ketones the way he does. So, did that sound about right? Did I miss something? Yeah, thanks. That was a great introduction. It covers a lot and we can dig into some little side things too that you know we study. So what are the five to 10 benefits of being in a state of metabolic ketosis and we can later discuss actually how to get there but what are the main benefits of being there? Yeah, I I think the benefits of uh dietary ketosis, we we do like to use the term ketone metabolic therapy because we do use it for the metab metabolic management of different uh disease processes. And more recently, we've been sort of proposing to do a larger project on sort of prevention, you know, uh using it as a longevity kind of protocol for uh an NIH uh project that we're working on. Uh so I I think you know from a from I use a ketogenic diet. I mean just I'm not managing any type of disease process but uh over the years about 20 years ago I started studying it and I wanted to be in a state of ketosis to understand uh what individuals have to do to achieve and maintain therapeutic ketosis that's defined by an elevation of ketones and sustained. And uh my background was studying seizures. So for seizure disorders, for uh neurop protection and general brain energy stability uh and I think really that's the common theme. Uh and probably the most credible information and evidence behind being in ketosis uh would be uh uh undisputedly it's it's that when ketones are elevated in your blood uh you can also measure
in your blood uh you can also measure them in your breath and in your urine. When ketones are available uh physiologically, they uh cross the bloodb brain barrier easily and they supply an alternative fuel for the brain and that can positively impact brain energy metabolism also the neuropharmacology of your brain and also it reduces uh systemic inflammation and neuroinflammation can be uh the root cause of different brain disorders and that could be seizures that could be migraines brains that could be psychiatric disorders. So you know this is relatively new information over the last 5 years maybe about 10 years ago it was key. So I would say brain energy neuroinflammation uh it reduces the uh insulin and people many people about about 50 to 60% of people over 60 have elevated insulin have insulin resistance. So, uh, suppressing the hormone insulin and that increases fat oxidation, uh, from your own fat stores and also dietary fat stores that you're eating. It helps sort of train your metabolism to burn fat more efficiently. Uh, there's an increase in mitochondrial uh, it puts a stress on your mitochondria when you initiate a ketogenic diet. And then that mitochondrial stress is like a a hormetic stress that enhances mitochondrial function. And ultimately in animal models it takes about a month or more to get increased mitochondrial biogenesis. And I think in the human studies too in athletes that are adapted to ketogenic diets they have more mitochondria more efficient mitochondria. Uh there's a reduction of oxidative stress. Um we are looking at different inflammatory markers that are really important for linked to autoimmune diseases. Uh we have a recent clinical trial at the Mafet Cancer Center. It's a national cancer institute center, one of the bigger one of the
center, one of the bigger one of the biggest ones I think in Florida. And we have a clinical trial using uh exogenous ketones that we call pharmarmacological ketone metabolic therapy to augment uh what's called immune therapy checkpoint inhibitors specifically in lung cancer. So we're starting that up to basically do a feasibility study to use this as like an adgiant. And then there's like epigenetic effects that we can go into or you know things on like visceral atapose tissue and things like that. I probably mentioned more than five there. But I think I covered like you know the main sort of the main reasons why we do and also I know you've had Dr. Thomas safe read on. So when you're in a state of therapeutic ketosis defined his definition is a glucose ketone index. So the ratio of glucose over ketones and achieving you know 1: 4 I think he likes the 1: 2 range. But I think in one to four you're getting a lot of benefits and that that can be effective for reducing cancer growth and also making uh what we study is like standard of care or immune based therapies work better and the patients get less side effects and they get a better response to treatment. Um you know and it limits glucose availability and also reduces sort of insulin and and various hormones that can influence cancer growth. that suppresses them in a way that sort of suppresses tumor growth in the large majority of cancers that are out there. That was an amazing overview. There are clearly multiple benefits of ketosis and we're just getting more and more information. I want to return to something that you said. You discussed about the ratio of ketones to glucose. So ketone glucose ketone index. So you said one to four or one to two. I guess an average person has is familiar with measuring ketones with the blood test and seeing like 0. 6 millles per liter. How does that actually like
per liter. How does that actually like practically look like when you measure your ketones like that? Yeah. Uh so in the United States we tend to measure glucose by milligrams per deciliter. So you know um so like you know a 100 milligrams per deciliter would be about uh 5 you know two or 5. 5 uh millimmers. So uh there's a device that oh actually I have here on my desk the keto mojo device which we use in our research. So I have okay you have one you're familiar with it. Okay so your listeners may may be uh familiar or people watching this. Uh so there are various devices out there that you can set the device to measure the millolar concentration of glucose and the same device using a different uh stick or sensor or you know uh thing that you put into the uh uh the meter itself will measure beta hydroxybutyrate hydroxybutyrate and uh it's important also to me to mention that it measures a particular anantimer it measures the D beta hydroxybutyrate And there are different forms of beta hydroxybutyrate. There's also accetoacetate and acetone. So it's not measuring them. And and when you're in a state of ketosis, it could be elevated. You could have D L acceto acetate and acetone. And we call that total ketones. So we measure like total ketones too. Uh so the ratio of glucose over ketones would be your uh glucose ketone index. And say for example if you were to achieve uh a low glucose level of 3 millmer which would be like uh 65 to 70 milligrams per deciliter uh and 3 millmer ketones that would be a glucose ketone index of one and that's for for many people you could achieve that through about three or three to five days of fasting. So that is difficult to achieve. Uh in the lab and even in the clinic, we're working on ways to consume
clinic, we're working on ways to consume exogenous ketones with other protocols that could within 30 minutes. You could go from a glucose ketone index of 20 to a glucose ketone index of one and with various dosing protocols maintain that indefinitely and that could be you know you could quickly induce that therapeutic ketosis. Um so yeah the glucose ketone index is simply the the millimmer ratio of glucose over ketones and it becomes uh a really important like single biomarker that is now used in registered clinical trials and we're using it for our research and uh so and it takes into account the the glucose which is a driver for insulin and then the ketones obviously which is has uh signals that the insulin is low but also uh The ketones have signaling properties that are really important for some of the work that we do. Right? So this index would be mostly relevant for someone who wants the enter into the therapeutic ketosis whereas in everyday life when someone is following a ketogenic diet maybe for just getting like more energy it's less important to get into such numbers. Would you say that's correct? Yeah, I I think for you know uh daily activity sort of your baseline metabolic physiology if you could have a glucose ketone index of 5 to 10 that would be significantly better than the general population which is probably always over 20 for example not really making any ketones. So uh so if you could if if you maintain a glucose ketone index of 5 to 10 which is achievable with just a low carb diet and maybe some you know MCT oil or like a little bit of ketone salts here and there uh that'll give you know there there's credible evidence to suggest that there you could derive a lot of benefits from that from your cardioabolic biomarkers that we can go
cardioabolic biomarkers that we can go into too. So, and and that's really like the big thing is that you know using a dietary nutritional ketosis and supplemental we call that umbrella term ketone metabolic therapy to shift the cardioabolic biomarkers in a way that can confer sort of uh brain energy but also uh brain resilience and also have anti-cancer effects for longevity. uh but it also impacts various hormone systems and signaling mechanisms that uh can really help with the longevity profile that someone is seeking. That's great. And I think I've been maximum between six and seven of this index and that's that's yeah that was when I was eating very low carb doing an experiment of a certain kind that I will probably talk later. Um, okay. So, you've been in ketosis for 15 years, which sounds mildly wild to us normal mortals. Actually, I didn't realize how long you've been in ketosis before last week when I was listening to your podcast with Mr. Sean Kim. And when you said that, like, I've been on a ketosis for 15 years. Yeah. Over. Yeah. I like you should have seen my face because my jaw dropped to like to the seat. Um um I guess you can find multiple benefits. What made you start in the first place? Like what made you start and maybe how did you what made you continue? Yeah. Uh so when I started research on the ketogenic diet and exogenous ketones, uh uh I I think I I kind of started for uh I was curious of the you know the the mental benefits. Uh the body composition changes. Uh I've never really had a lot of fat mass. I've always been kind of lean but at the same time sometimes I wanted to you know reduce my fat mass or just u uh change my body composition periodically or
my body composition periodically or situationally. Uh so it was a is very effective tool for that and uh what I was always concerned about is that ketogenic diets would cause muscle loss and like you know uh rapid weight loss and muscle loss but uh that was pretty much a consequence of like a lower protein ketogenic diet which is used clinically uh in the world of epilepsy it's like you know uh 10 to 12% protein. So the even the modified versions of the ketogenic diet that we advocate for have about 18 to 25% protein and even we have a sort of an engineered rodent or animal ketogenic diet that doubles the protein. So historically you know in animal research they use about 8% protein to 10. So we doubled that and I think we have about 22% protein even in our cancer uh you know studies that we've run a half dozen you know cancer cancer uh publications we have uh many of them with Dr. Thomas Safe who you interviewed. Um so after following a ketogenic diet uh you know over over the years I would would always keep modifying it and adjusting it and personalizing it to me based on food preference and also based upon my blood work and my biomarkers and also subjectively based upon like my energy uh muscle mass, my DEXA scans, things like that. and and I did, you know, following a standard ketogenic diet and doing intermittent fasting, which about 1015 years ago I was doing that quite often. I lost a significant amount of lean body mass and that did not occur to me uh until I did like more comprehensive, you know, DEXA scans and things like that. Um uh however I did not you know necessarily want to gain more muscle and uh but I wanted to as you know I started doing this in my early to mid30s I guess and now I'm in my 50s. So as you get older especially in your 40s to mid to late 40s and even
in your 40s to mid to late 40s and even like once I you know got turned to 50 it becomes increasingly harder to maintain your strength and your muscle mass. So, I've had to sort of adjust the protein levels up a little bit. And that kind of kicks you out of ketosis or doesn't you're not achieving as high as ketones. So, I've been relying more just on a a low carb diet, a low carb Mediterranean type diet, if you want to use that term. And then adding things like MCT oil and also exogenous ketone electrolyte salts. Occasionally, I use uh we do research on ketone esters, too. So, sometimes periodically I'll use them. uh a little bit less so now, but we've developed some new uh novel types of ketones that I've been experimenting with. Uh so yeah, I I probably just do it mostly for the brain benefits and the energy benefits because in academia you have to spend a lot of time at the desk writing, being able to focus um and it becomes really important to keep your energy and metabolism sort of uh stable and and going. And if you have fluctuations in energy, especially in the mid part of the day, which was really common before I started the ketogenic diet, I always always had that dip in the early to mid-afternoon. And I don't get that at all when I stay in ketosis. All right, that's that's interesting. Okay. So, um I want to cover a lot of the practicalities with ketogenic diet, exogenous ketones a bit later, but first I'd like to discuss some of the research, especially the new one. So, according to CDC and the recent surveys, up to 30% of adults reports persistent general fatigue. So, third of the people are walking halfrained or feeling like they're walking like in in a fog. Um the brain is of course very extremely sensitive to depletion of any energy substrates and information.
any energy substrates and information. And these would typically immediately have have an effect on cognitive performance whether it's attention, short-term memory, working memory, focus, things like that. So probably one of the most notable effects of ketogenic state is the one that you mentioned this kind of mental clarity or sustained energy. How does actually work in the brain? Like what why does it induce this kind of sustained energy state opposed to eating quote unquote normally? Yeah. And I think it uh it will have a much bigger effect in people that have some form of a deficit deficit. And that deficit can be due to uh you know as we age there are we have general like cognitive decline as we age but also in people that are younger that are experiencing stress, lack of sleep. You know, we study extreme environments. That could be uh hypoxia, uh sleep deprivation, um what we call different uh a term that's used like in military and and space research is allostatic load where you're trying to like you know, you have a whole bunch of tasks, you're trying to juggle a bunch of tasks at one time. That's your like allostatic load. And also uh another term is like team cognition which if you're working with a group that you uh your your mood and your behavior is such that you're you're working very cohesively within the group and you don't have fluctuations in mood and energy that could sort of disrupt the uh team cognition. So these are like some of the terms my wife is more familiar with them as a behavioral neuroscientist. Uh but I think the real benefits are that you know if you're eating a standard American diet and we use that as an example uh you're eating primarily a carbohydrate-based diet and when you eat it your postprandially your glucose will come up and then uh for many people glucose goes up in the blood and then your body
up in the blood and then your body releases insulin and two to three hours later depending upon the meal the level of protein in the meal fiber even fat uh if those are not sufficient and balanced you could oversee uh insulin and then you'll have two two to four hours later you get a postprandial dip in your glucose which is very which was I was experiencing and that that dip in blood glucose would be sort of subjective hypoglycemia hypoglycemia uh for for many people and that can lead to brain fog that can lead to uh hunger cravings that could lead to a headache um and then can you elaborate what you mean by subjective of hypocamia. Yeah. So, uh for example, if if someone has, you know, I'll use it in the context of type two diabetes because, you know, working so if someone with type two diabetes that has like a high level of glucose. So, if we look at the NHANES data of people over 60, 50% of them have pre-diabetes or overt type two diabetes. So, their glucose could be running 130, 140, 150. If their glucose goes down to 100 or even 90 uh in millimmer concentrations that would be like four that would be normal they are experiencing uh uh subjective hypoglycemia and and a lack of brain energy right because uh so uh and the the lack in brain energy can lead to brain fog fatigue and things like that so it's subjective meaning that you can feel it right um and even in a normal like I mean me for example you know I don't have any kind of overt pathology at all, I'm fairly good insulin sensitivity. And when I do get reactive hypoglycemia, meaning that if I have some fish and rice or some pasta, breads or sandwich or something like that, uh I'll feel good maybe for the first hour or two, but then in many situations, uh two or two to four hours later, I'll have a dip in glucose where I just feel a little
in glucose where I just feel a little bit sleepy and I don't feel that energy flow. And what's happening is that if your body releases insulin, it's facilitating glucose uh disposal into peripheral tissues like your muscle and other organs. And then you have a lack of optimal brain brain glucose. So it's limiting the brain glucose availability to your brain. uh if your body oversees uh insulin or if you're you get that dip in blood glucose and especially from a circadian rhythm point of view like in the mid part of the day uh when you know uh you're experiencing the morning a lot of people can wake up and feel I have a pretty strong like cortisol response in the morning and then it goes down during the day but uh uh you know if if you're not getting sufficient sleep and stuff you'll many many people report over 50% that they get like postprandial sort of fatigue after lunch there. This is very common and it could be due in part to just not getting optimal sleep. But I I also sort of attribute it to uh blood glucose fluctuations going low. So that's a subjective. And when you're in a state of ketosis, even if your gluc your ketones are moderately elevated to 1 millmer and that's like moderate ketosis, one millolar glucose or ketone in circulation will contribute to a 10% increase in available energy to the brain. So all these uh a very uh elaborate sort of metabolic physiology was done at Harvard Medical School by George Cahill and Oliver Owen and they looked at the AV difference of brain use of glucose and ketones and really nicely established that uh about you know if your ketone levels are four to five millolar that's that represents 40 to 50% available increase in brain energy to that. So that would require your brain leading needing less glucose to
brain leading needing less glucose to maintain normal energy. So the the practical, you know, real world advantage is that if your ketones are elevated and you experience mild hypoglycemia, you're asymptomatic for hypoglycemia and that's not triggering the fatigue, the craving, and the cascade of things that happen during that subjective. And and a lot of people don't know that and I think that's like important. And there's actually research going on right now in diabetes and type two diabetes using ketones as sort of like a insurance against hypoglycemic shock and and low low glucose. So, I think that's uh and I I've experienced that uh when I started experimenting with ketones and experimenting I won't mention how I did it but I was able to bring my glucose down to where the glucose meter would not even read the level of glucose and as long as my ketones were elevated and I did that with exogenous ketones I was at a glucose level where I should not even be living or I I experienced you know I was asymptomatic for hypoglycemia And I was experiencing fatal level of hypoglycemia according to like you know what I teach at the medical school. But because my ketones were elevated, I was perfectly normal and fine. And that kind of replicated the work that George Cahill did at Harvard 1967 where he injected subjects with 20 IUs of insulin, put them into what would be fatal hypoglycemia, but because their ketones were elevated, those subjects who fasted 40 days were asymptomatic for hypoglycemia. And reading those early papers that could these types of experiments can't be done today, but reading those early papers got me very very motivated to figure out ways how we could achieve that same level of ketosis independent of having to fast for 40 days or independent of a very restrictive ketogenic diet. So that sort of I I pivoted my research away from pharmarmacology research to more ketogenic molecules, keto ketogenic
ketogenic molecules, keto ketogenic diets and exogenous ketones, you know, uh about 15 20 to 15 years ago because of some of these seinal work. Yeah, it it's it's a very powerful stance that you have you're both like extremely passionate about ketones, the study of ketones. Uh you have a high level academic degree on it. conduct research, mentor research, and you self-experiment. Have you ever been worried about self-experimenting with maybe that relates to your story that you I didn't want to share, but have you ever been like worried of self-experimenting with any state of metabolic ketosis or like exogenous ketones? Because Yeah. I mean, I guess that to some extent it can be a bit dangerous if you don't know what you're doing, but you obviously do, but for for maybe someone listening. Yeah, I would not advise people do to do what I did in early experimental. I I did it under very methodical situations. I did it according to published literature. Uh I did it with a lot of uh you know safety contingency plans if something was to go wrong. Uh but there there's things that I did in you know 15 20 years ago that I would not do now when I first started getting into this because uh when I was reading the literature I I almost became very skeptical of this idea that our brain could just like quickly get into ketosis and my understanding was that you had to adapt slowly over time. Uh but I had many conversations with the icons in the field and some of them were uh Dr. Richard Vch uh of the NIH he was mentored by Hans Kreb of the Kreb cycle. So he was the first to really develop uh a ketone Esther and that was being used uh or funded by DARPA to in in a war fighter optimization program. So that that caught my attention and I was able to dig up some documentation that this research was being done and I wanted to
research was being done and I wanted to sort of use that strategy for seizures and things like that. But I also talked to the late uh Dr. George Cahill uh Dr. Theodore Van Italy, Dr. Sammy Hasham. Uh I don't think none none of them are alive today, but I had the opportunity I was very fortunate and grateful to be able to talk to them and they convinced me that if you could acutely elevate ketosis or ketones that that would give uh a major benefit to your brain, it could be neurop protection and it had all these tremendous potential. So they did the foundational work and I just came in to basically you know uh continue what they were doing develop you know some additional molecules and I think what we did is apply it to different different circumstances. So that could be uh you know enhancing cognitive function uh many different genetic disorders, Angelman syndrome, Kabuki syndrome, uh Pompei syndrome, glucose transporter type 1 deficiency. So there's a whole list of different we have like these animal models of the disease and I would say that that exogenous ketones have worked better than any drug that we have. Uh and that would also hold true for seizure disorders. So oxygen toxicity seizures limit hyperbaric oxygen therapy. It also limits Navy Seal diving. And when we administer this to animals, it works better than any anti-seizure drug. So the level of anti-seizure drug that would even come remotely, you know, similar would put the animal into like a coma. It would So we were giving an indogenous metabolite and that would prevent the seizures better than any drug that I had had ever used. So and that was early experiments. So that kind of set the stage for thinking, oh okay, I need to study this more and I need to expand the applications into things like cancer and other applications. [snorts] I want to share you with you a story and the listeners a story that I think you might find quite fascinating. So I had a
might find quite fascinating. So I had a mold illness whether or not people believe in that diagnosis but it is a new condition. We we know now that micotoxins can cause multi-system multi-organ inflammation and that can affect cognition. So I conducted cognitive testing on myself, neurocognitive testing and also I did the integrated visual and auditory continuous performance test as well as quantitative EEG at the time because I felt extremely brain fogged and I noticed I my brain didn't have the neurotypical ADD pattern in how it functions but my performance was ADD. So I scored ADD in the neurocognitive testing. So and it was clear that I had like big mold exposure. I had inflammation. All the markers came out pointing on that something has something inflammatory is going on due to this mold and it's affecting my cognition. So I did the whole mold protocol, not the shoe maker one but just the the medication and some peptides, some supplements and I also decided to use the elimination diet. I did a carnivore elimination diet because my body was extremely reactive. So carnivore elimination diet for those who don't know is a type of a ketogenic diet. So you can go into ketosis with that diet and that is when I started measuring like daily the glucose ketone index as well because I had just recently interviewed Dr. Thomas Seaf and I was like oh this is a new index I can actually measure. I've been measuring my ketones for a long time and glucose, although I'm not always in a ketogenic diet. Um, I eat Mediterranean. So anyway, I scored AD and I did that diet. I did the medication and I did hyperbaric oxygen therapy for 20 times and that helped and then I did neurocognitive testing again and all of my markers were normalized like everything. So it was of course a
everything. So it was of course a combination of multiple things but here I was really contemplating like how much did the ketogenic state made a difference not only elimination part but actually the combination of ketones with hyperbaric o oxygen therapy and age is another research field of yours would be like very interested to hear what do you think about this this phenomena because I'm still like trying to wrap around what what really happened here. Yeah. I uh so hyperbaric oxygen has a lot of advantages that we're just starting to to learn about. So uh I would preface it by st by saying that my career as a post-doal fellow uh got started in 2004 got started by studying the negative effects of high pressure oxygen. So we call that uh oxygen toxicity. So oxygen toxicity can come can you have central nervous system oxygen toxicity and also pulmonary oxygen toxicity. So but but we're talking about a level of oxygen that in our experimental model we use five atmospheres of oxygen and that will produce a seizure in a human in about 5 to 10 minutes. the up the upper range of uh you know oxygen level would be uh three atmospheres of oxygen 100% oxygen so we are breathing at if we're at one atmosphere 20% oxygen uh you know at one atmosphere so that's a 0. 2 to ATAB um oxygen uh absolute. So in in hyperbaric oxygen therapy you saturate the chamber or you breathe 100% oxygen and then you increase the barometric pressure uh upwards two additional atmospheres you know and that would be upwards of you know you could go to two or three ATA optimal you know the the maximum load and what that does is
maximum load and what that does is independent of hemoglobin it gets oxygen into the the fluid component the plasma so that allows the brain to get hyper oxygenated when the brain is hyper oxygenated. Oxygen is a stimulant. So it can increase uh glutamate. It can increase neurotransmitters. Uh hyperbaric oxygen uh when you use different protocols and the Israelis has developed different protocol. It it can also optimize stem cell production and the release of stem cells uh from various tissues including you know individual organs but also uh from the bone marrow. It it releases stem cells into circulation. Many people don't know this, but this is work done by Dr. Steven Thom origin. He was at University of Pennsylvania. I think he's at Maryland now. Uh that it would correlate to to a drug called Nupagen or GMCSF. So that drug is used like in cancer patients to boost like stem cells to get the you know your stem cells up and running again. And hyperbaric oxygen like almost stimulates the same amount of stem cell release. So not only the production but also the release of these stem cells. So that underlies its application for the the use of hyperbaric oxygen for enhancing wounds and when you have an injury to the brain. Uh even a seizure creates like a bit of an injury. So uh we think about hyperbaric oxygen as sort of enhancing the wound healing effects to the brain but it also has pleotropic effects and in the context of something like cancer it can sight specifically augment cancer thrives in a low oxygen environment and when you reverse tumor hypoxia and hyper oxygenate a solid tumor it overproduces oxygen free radicals similar to a way that radiation and chemotherapy they kill cancer through a a oxidative stress mechanism. When you do it with hyperbaric oxygen it's much more gentle to the system. You're actually getting you know benefits to your healthy tissue
you know benefits to your healthy tissue while you're stressing in some cases killing like the tumor. And what it does is it sensitizes the efficacy of radiation therapy is proportional to the P2 of the tumor and also the redux state of the tumor. So if you couple hyperbaric oxygen with radiation therapy or you do it in and around the same time it can sensitize the tumor to radiation therapy but also chemotherapeutic agents that work through a redux mechanism. Uh so these are just some of the you know things that we study in the lab but but h generally speaking hyperbaric oxygen can uh enhance your physiology it can enhance stem cell production. It can enhance uh brain energy and we are right now it's a double blind it's a blinded controlled trial but at University of South Florida we're do we're doing the biggest hyperbaric oxygen study that has ever been done. So we on uh uh traumatic or mostly traumatic brain injury with or without PTSD. So that study is in process and it's actually using a sham where we give a pulse of pressure in the beginning to make people think they're having hyperbaric oxygen therapy. Uh but we're keeping it at one atmosphere and we have you know the treatment group. Uh so these are veterans that experience traumatic brain injury and there's some of them uh most of them don't have PTSD but some do so. So it's with or without PTSD. So that's an ongoing project and I think it'll clarify the utility of this therapy for uh for brain injury and many of the patients get headaches, brain fog uh and have like symptoms similar to what you describe to and many of them maybe they do have we haven't checked but many of them may have an infection and that could be bacterial like Lyme disease that could be fungal that could be viral right Epstein bar CMV HSV uh so various virus viruses too can sort of uh affect the neuroinflammatory state of the brain and I think this is
state of the brain and I think this is underappreciated and I think it's an emerging area of research that things like like herpes simplex virus you know uh is a driver for Alzheimer's disease that's being studied I think the chair at Harvard is sort of spearheading this idea there was a NIH funded workshop you know discussing that and and hyperbaric oxygen has like a lot of utility for some of these All right, this is super interesting. Um, not to deviate too much from the ketones, but I just wanted to mention this because there is an actual article that that this is why I initiated the treatment because there is actually an article where they took 15 previously healthy individual who had mold toxicity and they developed ADD symptoms. they used hyperbaric oxygen therapy for 15 to 20 time if I'm not mistaken. I'll link the paper of course and um yeah they they a lot of them got a big improvement or reversal of the ADD with with this and uh they just did 1. 3 ATA and I myself I did 1. 6 so that was like a still mild mild thing. Okay. Yeah. That's underappreciated too. So, you know, for wound healing, diabetic wounds, carbon monoxide poisoning, decompression sickness, we tend to go high because, you know, if you have carbonoxide sickness, you know, the carbon monoxide is attached to the hemoglobin and you have to push it off with as much oxygen as possible. So, you push the limits. So hyperbaric oxygen clinics tend to use the the maximum tolerable dose whereas there's a lot of uh benefits and research to be done with these more mild doses that that you're experiencing which can be achieved with a soft shell chamber and not necessarily like a big steel hard shell chamber which is very expensive and it would be it would also be expensive to pay for that for the person wanting to get benefits. There are soft shell chambers available now that could
shell chambers available now that could be much more affordable to to get the benefits of hypogaric oxygen therapy. Yeah. The prices in states are definitely a different different than here in Europe for age both. So I appreciate it's a bit more difficult to get into get like a 20 times treatment there. But going to other some other neurological conditions or conditions that affect the brain. So you serve on the editorial board of Frontiers in Psychiatry as an editor for metabolic approaches for mental health. So this kind of nutritional psychiatry is an emerging field of research. I don't know if it's still emerging or already well established probably established at this point but it's it's one of the most fascinating fields for me personally and one of the most fascinating books probably in this field is brain energy by Harvard psychiatrist Dr. Chris Palmer. So based on your research and experience can a ketogenic diet or exogenous ketones help with mental health? Yeah, thanks for bringing up this topic. I think it's an important one. Uh, I'll quickly say that metabolic psychiatry or nutritional psychiatry is underappreciated underappreciated and from a conventional lens from the practitioner who's a psychiatrist uh many of them don't even know about this and I think it's it's important to get the information out there. uh and many of them are not skilled in the science and the art of uh of giving this therapy and and that's that's a gap that we have in our treatment. uh but also there's a gap in the science but as you mentioned it's an emerging sort of field that it makes sense right food affects mood that's you know that that's everyone has to sort of agree with that and then also our our general metabolic health impacts food so that's like a statement I think everyone knows and appreciates what they don't know and appreciate is that the the state of
appreciate is that the the state of therapeutic ketosis has very specific effects on brain energy and we have to credit uh Dr. Christopher Palmer from Harvard who spearheaded his book Brain Energy which I was uh fortunate enough to get an advanced copy and read it and just like was really inspired by the work. Uh also Dr. uh Shabbani Sethi at Stanford has a metabolic oncology like division or clinic and I think she's spearheading this too and there are well over a dozen sort of research scientists and practitioners you know and a lot of it is spearheaded by the Bazooki group uh Jen and David Bazooki you know through philanthropy they're they're funding these efforts but now uh and I think it this is important to mention too there are registered clinical trials that uh and some of them the NIH is funding. Um, and I had the stats here. I was just on clinical trials. gov and I think for psychiatric disorders there are over 50 uh registered clinical trials. Uh, and that includes bipolar, major depression, anxiety, schizophrenia, uh, anorexia nervosa. Uh, Dr. Guido Frank from University of San Diego has a couple large trials and publications that came out recently. So uh anorexia nervosa kills more people than than any other psychiatric disorder. So that was interesting to listen to his research yeah this is an emerging you know area and it's kind of counterintuitive too because I have a colleague at University of South Florida that studies eating disorder there there's eating disorders and disordered eatings and they go into different buckets but I think you know rightly so she was skeptical of the idea that that a highfat ketogenic diet but then you know as the science emerges then you know now now people that were skeptical are now accepting that this could be a viable therapy. Uh so I would say that you know metabolic psychiatry is is emerging and I think uh at the
is is emerging and I think uh at the very least it's it's considered as an adgivant to uh drug therapy and and so what we do know I I teach uh I teach the antiscychotics and I teach the different drugs. So we do know that the atypical antiscychotics are often the go-to drugs for people that have psychiatric disorders and the atypical antiscychotics cause pretty profound metabolic consequences. So that would be weight gain, insulin resistance, elevated blood glucose. The this is well known and established and it's something that I've been teaching you know for I don't know over 15 years. So uh a a good you know application for ketogenic therapies is to to reverse and prevent the the side effects that some of these things and that's like in conventional psychiatry that's sort of like the barrier to entry. So how can we make the current standard of care work better and how can we increase uh decrease the side effects. So there's some uh one or two studies funded sort of looking at that but also the ketone metabolic therapy in and of itself as a therapy and to basically help deprescribe some of these SSRIs and antiscychotic drugs that are quite problematic for people and also like people with psychiatric disorders even PTSD they tend to self-medicate so they go to things like uh marijuana they go to you know cannabis they go to alcohol they go to benzoazipines, they go to, you know, opioid type drugs and that has been historically very problematic like in the uh the the communities that I've been associated with like the veterans community and things like that. So where where I think these nutritional have have a lot of potential to help even with substance use disorder is a in in the bucket of psychiatric uh illnesses and diseases. So I think there there's also registered clinical trials on the use of ketogenic
clinical trials on the use of ketogenic diets and now more recently we can talk about exogenous ketones too because some of the diet studies have already been done and those same researchers are pivoting to not using a diet therapy because that's hard to do for this particular demographic or patient population where exogenous ketones can fulfill uh many of the benefits probably not all the benefits of dietary therapy but also they're not mutually exclusive. So you could use a diet therapy that is less restrictive and then combine that with exogenous ketones to further augment that diet therapy. So this is uh many people who have studied ketogenic diet therapy are pivoting to the idea of using exogenous ketones or coupling the ketones with diet therapy. Right? Okay. Let's discuss the diet therapy. Before that I'll briefly ask about um so there is promising research around psychiatric conditions then one of the most brutal fates is a neurode generative disease I would say I watched my grandmother slowly fade away with Alzheimer's and it's it's very hard to watch so in dementia the the brain's ability to use glucose is declining even before basically overt symptoms While if I understood correctly, the capacity to use ketone bodies appears to be relatively preserved. So, can ketones or ketogenic diet be applied to dementia? What does the research say? Yeah, it's good you you bring that up and that's sort of work that has been done by a number of different groups and I think uh Dr. Steven Kunain was the first to show using a glucose PET scan coupled with a ketone PET scan showing that uh as brain glucose uh utilization drops as we age uh brain ketone utilization is largely preserved and that is that's suggestive of a
that is that's suggestive of a bottleneck of energy production uh with glucose metabolism. So with glucose metabolism, there's a lot of different areas where the the metabolism can be impaired. So that could be, you know, you could have vascular dementia. It could be a blood flow problem. And then the ketones uh increase uh per uh it increases cerebral blood flow like even acutely about 10 to 20 to even one experiment uh 30%. When you get into ketosis uh and that has to do with the vascular endothelium. So you have uh a hallmark characteristic of Alzheimer's that is now accepted is that there's glucose hypom metabolism. So you mentioned that uh 10 years ago uh if I said that that would not be people would not agree agree with that but now Alzheimer's centers will even agree and people who study Alzheimer's will now agree that it took a while but they agree that glucose hypom metabolism is a hallmark characteristic of Alzheimer's and even mild cognitive impairment and even things like Louisbody dementia and things like that. So uh so you have with glucose metabolism you have the bottleneck could be the glucose transporter so not not the glute one but probably the glute 3 so that's on neurons and also an enzyme called pyuvate dehydrogenase complex uh PDH and they tend to be like and if you have brain injury or Alzheimer's disease the proteins if we do like uh western blotss or something like that to measure the protein levels are always lower for like pyuvate dehydrogenase complex the protein levels and the catalytic activity of that enzyme is well established that it's much lower in especially with advanced Alzheimer's. So we know that that glucose metabolism is a bottleneck whereas ketones can readily cross the bloodb brain barrier the the cell membrane and the mitochondrial membrane to quickly you know generate ATP or to
to quickly you know generate ATP or to generate the reduced intermediates that drive electron transport chain. So we know like you know mechanistically how that works. So we know the rationale is very solid the scientific rationale but we have not put that into practice yet. So uh and even you know the the I've talked to many people who study Alzheimer's and the big drugs are the monoconal antibodies that you know target the amaloid beta or the tow proteins and it's now it was very controversial 15 years ago to say that amaloid and tow accumulation is a consequence a downstream epiphenomenon of neuroinflammation uh and other things. But we know that you know even over 10 to 15 years ago if you inject LPS lipopolysaccharide which causes inflammation into like mice that they quickly accumulate amaloid in the brain. So and and generally speaking if we have a higher state of systemic inflammation that leads to neuroinflammation that rapidly causes amaloid and towel plaques to accumulate. uh and that that inflammation can be triggered by uh a fungal disease could be triggered by micotoxin by you know bacterial uh a viral illness. So uh you know now so we have research that's being funded if you go to clinical trials. gov I think there's well there's over a dozen clinical trials looking at ketone therapies and the ketone therapies could be a ketogenic diet. There's a few with the ketogenic diet. There's several on mediumchain triglycerides and also several on exogenous ketones. So ketone salts, ketone esters, and various ketone precursors. Uh 10 years ago there was none. So now we have over a dozen uh registered clinical trials. So what happens is that these types of studies need to be done over over a protracted time frame. If it's a NIH RO1 grant, you're talking like, you know, 3
grant, you're talking like, you know, 3 to five years. a U19 grant, you're talking like, you know, seven years of research there for that research to be confirmed and then published in peerreview for it to be accepted by the scientific community. So, uh it's so it's an emerging topic. The rationale is there, but it is not in the it's not part of the tools that people who help people with Alzheimer's uh are using at this time. All right, that makes sense. Thank you. That was Yeah, it makes total sense. uh we are looking hoping that there will be more research funded one way or another on this topic because it is important. So do you think ketones or ketogenic diet and longevity can go hand in hand? Yeah. And I think you we have to take a very nuanced approach to that too because uh yeah, you know, I mean, I'll just mention that a ketogenic diet that's that's really high in fat that is sort of the classical kind of dairybased ketogenic diet that's used for epilepsy. Like I started following that initially and my blood work indicated that you know my LDL cholesterol was like over 300 at one point and my APOB which is probably a more accurate indicator was also elevated into the one mid60s above 160 and uh and then my triglycerides started to creep up a little bit but they were still pretty good. Everything else was good. You know I could say like most of my cardio biioarkers were were very good. blood pressure was lower, you know, hemoglobin A1C was lower, triglycerides were creeping up if the diet was very high in fat or if I had surplus calories, if I was trying to maintain my weight or even gain weight. So, what I've experienced is that I've shifted away from very high dairy to uh minimal amount of dairy, maybe sour cream, some fermented dairy, uh but shifted away uh shifted more towards fish. I do get beef. We live on a farm. We got cows. We got, you know, all
We got cows. We got, you know, all around. So, I have access to like, you know, grass-fed beef, uh, eggs, and then, you know, things like broccoli, greens, wild berries, uh, some walnuts here and there. Um, you know, and I have like kind of a mix and some fruit, too. So, every day I get, you know, a little bit of berries, I mentioned, and maybe like one small apple. Total carbohydrates for me, uh, is about 50 to 100 grams per day. And that diet, the diet that I just described, it's a little bit more mixed. I'd call it a modified ketogenic diet that's higher in protein. Probably upwards of about 30% protein. Uh how much do you eat protein? Yeah. Uh 30 some days maybe like 40% of my calories are protein if my fat is dropped a little bit. But I generally do about one gram per pound, you know, and I'm So that's about two grams per kilogram. Yeah. So, I'm, you know, just about a 100 kilograms. So, I'm taking in about 220 grams of protein a day is kind of what I do. I'm kind of taller and bigger. So, uh, I need that amount of protein really to maintain my current level of of like muscle and strength. Uh, you know, not everybody needs that much. Not everybody's into like, you know, working out or wanting to maintain, you know, a certain level of strength and and size. But I think for me and for someone who's very active, who may be doing a lot of activity, that that is the upper end. You definitely don't need any more than that. And I think you could get away with, you know, uh you could get away with uh less like you could get away with like, you know, if we're doing the the kilograms, like 0. 6 to 0. 8 grams per kilogram and be fine. Like I could probably do and some days when I'm traveling and do things, maybe I'll just get 100 grams of protein, right? And then some days, you know, occasionally I do three-day fasts and that could be uh if I do it with like a sardine fast, right, I'm getting, you know, like 60 grams of protein a day or something like that or a little bit over. Interestingly, that's like the RDA
over. Interestingly, that's like the RDA recommendation of protein with that type of fast. Um, but I do believe that the high omega-3 content and, you know, the types of foods that you eat are really important uh for your cardiovascular health if you're going to think about this as a long-term strategy. if you're going to do and I do think that you need to consider you know looking at adding other biomarkers to your blood work that would include fasting insulin hemoglobin A1C HSCP triglycerides apo and also it's probably good to know your LP little A so that particular lipoprotein and mine is elevated and because my apo was elevated even on a diet that's higher in fish and like some nuts and olive oil and things like that. My apo was was elevated above a above 100 to like 120, but I use a I I take a small dose of a drug called aettoide and that blocks the NPC uh 1 L1 a transporter. So that transports that that's involved in cholesterol absorption in the gut also plays a little role in the liver. But a very small dose 5 to 10 milligrams per day if someone is a hyper absorber of of cholesterol will drop for me because I do have a genetic mutation for that that I found out with some genetic testing that dropped my apo from 160 when I started. Now it stays about 80 now. Some people would say that's even a little bit high but that's way lower. I cut that in half and u you know that's a very small dose of a drug that essentially has no side effects and maybe some other beneficial effects on Alzheimer's. It has some some interesting effects like in the brain. It does cross the blood brain barrier and in the brain it has some protective effects in the brain. There's some research behind that too. That's interesting. Would you say homo sustain is an important marker? That's what I measured when I was doing it just
what I measured when I was doing it just to, you know, make sure that it's not elevated too much. And then it was like it went to like 13 for me and then I took TMG for four to six grams a day and that lowered it to 5. 7. Oh, okay. My wife takes uh that and I I'll take it situationally occasionally. I've measured that. Mine is in a pretty good range, but it would be I've heard that that TMG is kind of gaining a lot more popularity. It was kind of popular back in the early to mid 1990s. I remember when I was kind of studying nutrition, uh people knew about it, but I I hear more people talking about TMG and they've reported what you're reporting like that drop in homoyine levels and and an animal-based diet can tend to like that can creep up uh and certain genetic predispositions can cause that to creep up. So, uh that's a good recommendation that I'm going to follow up on and actually do a study now. I [clears throat] have it in the home. So I might uh measure my homoyine and then reme-measure. So you said three to four grams is what you take. Four four to six grams. Four to six grams per day. Okay. I'm going to try that. So yeah, I would recommend that based upon what you just said and and what I' I've seen some recent literature on it and like anecdotally I mean at least four or five people have told me what you told me. So that's an interesting I think we should be I should probably pay more attention to my homo system. I've measured it, but I don't consistently measure it like I should. Yeah. I I'd love to hear your experience on it as well. Yeah, I'll follow up. Yeah. Thank you. I appreciate it. So, there are we just covered like previously that there are exogenous ketones that you can elevate blood ketones with. Then there is also the ketogenic diet. So, there are multiple ways to elevate blood ketones to induce ketogenic state in the body. So um what are the different ways and how would you rank them in you know what is like the the easiest approach that suits almost anyone and what is more extreme that may
anyone and what is more extreme that may be to be cautious with. Mhm. So, I like to start like with what has the the longest track record for safety, for e efficacy, and also in the uh the peer-reviewed clinical literature for ketogenic agents. So I would ha if I had to rank it according to what I just mentioned uh I think the first thing if you can tolerate it the first thing that I would recommend is mediumchain triglycerides MCT oil uh so that comes in the 8 carbon and the 10 carbon and I've experimented with pure 8 I've experimented with pure 10 but mostly what's sold as MCT oil on the shelves is a combination about 60% C8 and then C10 10. Uh so if you can tolerate it, you know, I would experiment very carefully if you have not tried MCT oil because it will lead to rapidly lead to diarrhea on at least for me even on an empty stomach and I'm adapted to it. But if you have a meal, you can add the MC you could take the MCT oil, you can incorporate it into it derived from coconut oil uh and you can incorporate it into salad dressings into your meal. If you take it with protein and fiber and and other forms of fat, you can train your body to basically absorb and utilize 50 to like even 100 milliliters per day. So I'm, you know, working with registered dietitians who use that. Uh but for some people it causes GI issues. So mediumchain triglycerides start with maybe 10 milliliters, 5 to 10 milliliters three times per day and that will further boost the keto ketone production in a low carb meal and a independent of, you know, even carbohydrate restriction. You can get ketone production with MCTs. So, that would be and they've been used for well over 50 years. MCT oils, they have a great track record and they're used for different inborn errors of metabolism
different inborn errors of metabolism too. uh like longchain fatty acid oxidation disorders and things like that because they're medium chain. Uh the next exogenous ketone I would recommend because has a long track record a really good track record uh you know I was just talking to an investigator that published in 2003 in Lancet on Lancet neurology for the use of DL beta hydroxybutyrate in multiple asil COA deficiency syndrome or deficiency disorder. So they were using upwards of 20 to 30 grams per day in these patients that had this inborn air metabolism and it reversed cardiomyopathy. So it enhanced the heart's ability to pump it, you know, reduced cardiomyopathy and uh and that that is a supplement that I take. So it's I take a a an electrolyte sodium DL uh beta hydroxybutyrate but it's like sodium calcium magnesium uh potassium is in it. Uh it's actually comes in a coffee. There's like it's one is keto keto spike. Another is keto start disclosure. My wife has a company based upon some various you know work that we did in the lab. We've published on uh so I don't have any like uh direct financial relationship with any company actually that sells uh or uh I don't have any equity or any financial stake in any company me personally with any ketones. I do I'll disclose that I do have patents that the university owns and then we have licensing partners that have ketone esters and exogenous ketones and things like that but that's the university owns like those patents. So I'll disclose that but I think the the that exogenous ketone has been used the longest amount of time. So that's like ketone electrolytes. So it's like you take it you get electrolytes and then you also boost ketones into the 1 to 2 millmer range. And I think for for daily
millmer range. And I think for for daily use that would be that's my go-to for daily use. Uh so the the next iteration would be uh very ketone esters. So that could be 13 butane dial beta hydroxybutyrate monoester or 13b butane dial uh accetoacetate diester. So we've we've worked with that molecule. We've worked with both of them and they are more potent and I consider them kind of like a ketone therapeutic a ketone pharmacological therapeutic because it does have 13b butane dial. So 13b butane dial is an alcohol alcohol uh and you can take 13b butane dial that's sold so different I'm not mentioning the companies but some companies sell what they call ketones some market them as ketone esters but they're not. So 13butane dial is a dial. It's a dialcohol. And when you consume 13b butane dial, it gets metabolized in the liver to beta hydroxybutyrate. But the liver metabolizes that exactly like it does ethanol. So you have uh you have alcohol dehydrogenase and then you have aldahhide dehydrogenase. So it spits off a little bit of aldahhide and then that could be toxic. So the liver has to work a bit hard to make to convert 13b butane dial to ketones. So what what researchers did is they took 13 butane dial and they added ketones to that. So we've done that like in our lab and we've used that for different studies. So that's a 13 butane dial associated ketone esester and you could put beta hydroxybutyrate or acceto acetate on that and when you consume it the ketones get kicked off they go into circulation so you get an initial peak and you get a bifphasic peak and about an hour or so later you get the peak from the 13 butane dial. So it kind of looks like it goes up and you get that phicinetic curve. So they they can be used kind of situationally. We use them for therapeutic, but also we did a
for therapeutic, but also we did a study, Ben Bickman did a study, we did a study, Ben Bickman did a study too and a number of other studies showing that 13butane dial can produce dependency much like ethanol. You can get dependent on it and when you stop it, you get you do get withdrawal symptoms from it. So I do not advocate for the use of 13b butane dial or 13b butane dial associated ketone esters to be used highdose chronically. So for someone that's managing Alzheimer's disease and other things, they're going to have to take the pro the take the exogenous ketone every day probably multiple times per day. And if you do that with a 13b butane dial or 13b butane dial based ketoneester, then you run the risk of you know progressively over time. So we saw some liver abnormalities. So when 13butane dial rapidly depletes the liver of something called NAD. So and you can see that very clearly in like the assays. So if you have even hepatocytes like in culture if you give 13butin it like depletes ATP and NAD. Uh the liver does have a good capacity to regenerate and it can adapt to that but only up to a certain extent. And also with older subjects their livers are not not as good. And if you take 13b butane dial by itself uh at at the maximum dose which is 30 grams per day a little bit over that 40% of subjects get dizzy and neither are like healthy subjects. So so these are all considerations. So but there are other molecules that are being developed. Uh the buck institute has a diester which is basically 13 butane dial with the m the C8 MCT essentially uh attached to it. So that's two. But I think if the a great combination to start with would be MCT oil and then ketone electrolytes, specifically the DL salts, which and then they taste good. You know, you can formulate the two together. Uh and there's like they have a solid track record of the literature. However,
record of the literature. However, they're less potent, but higher ketones is not always better. So I'll say that. Yeah, for sure. Yeah. So that that when your ketones get too high that becomes an acidic load that the body has to eliminate. Then you could get reductive stress. So it's called when your ketones get really high it can produce a redux shift which is called reductive stress. And then your body has to work hard to eliminate the ketones. You see them in your urine and uh and yeah but it creates like this mild metabolic acidosis that being in ketosis does and I know that that can be offset by the electrolytes. So that's why I like the ketone electrolytes. If you take a ketone esester, so that acidic load is not mitigated, but ketosis does, people don't talk about this. I think there's a guy that uh Nicholas uh he's big with magnesium and talks about salts, the salt fix. I think he has the book. I'm blanking on his name, but uh but he has he's been a little bit antagonistic to the keto ketogenic diet group, saying that ketosis does produce an acidosis that should be mitigated by higher salt, magnesium, and things like that. I'm of the opinion that that he's pretty correct, and I so that's why I like the idea of delivering the exogenous ketones with a salt with with the electrolytes. So I I think you were referring to Dr. James Dol Antonio. Yes. Sorry, I just Yeah, forgot. We're blanking on his name, but yeah, we actually recently co-authored a book with him, The Science of Okay, so you're on this topic. Yeah. Okay. Yeah, I I have had him in my podcast about salts. Uh I find the topic quite fascinating, but please tell uh please tell us the name of uh Dr. Tila Dakno Diaost company so we can check out the the supplements. Yeah, it's called uh Audacious Nutrition. So, I don't know if you could see that, but keto starch is, you know, one of the products. Uh, and it's got,
one of the products. Uh, and it's got, you know, uh, sodium, uh, DL, beta hydroxybutyrate, and then, uh, it's got, uh, magnesium, calcium, uh, potassium. It's got the mix. So, it's like kind of like the supplement electrolyte supplement element, LNTt, but the the electrolytes are bound to ketones. So, when you take it, you get the electrolyte benefits. And then so what I'm drinking here uh is uh Keto Spike, which is like a Colombian coffee. Uh it is this one's decaffeinated. Uh I have regular caffeinated coffee and then I follow that up later in the day with decaf. Uh but Keto Spike, so she has keto spike cocoa, which has the DL beta hydroxybutyrate, and it has a very high bioflavonoid uh cocoa powder with like tested [snorts] for like heavy metals and things like that. So, it's very a really clean pure product. So, there's keto spike cocoa, keto spike coffee, keto spike tea, and then the keto starch, which is just like uh it's lightly sweetened with monk fruit. So, it has like a pinch of monk fruit to offset the bitterness of the ketones. And that's kind of like my go-to uh you know, supplement that I use throughout the day. And I do I take another product uh keto brains which has uh uh it's really it has theine eltheanine it's got lion's mane and it's got uh alpha GPC with uh MCT powder. So, occasionally, not every day, I put that in my coffee, but I also take it at night time and I mix it with like a little keto uh mousse pudding thing that I do like a chocolate pudding and I put the keto keto brains product in that. So, for MCT. Yeah. When you said moose, I thought you you referred to the animal moose that you made like a pudding with that and then I was like that's interesting. Moose. Am I saying it right? Yeah. They might have different words in Europe.
might have different words in Europe. Yeah. Like a pudding type. Yeah. And Yeah. My pudding is actually it's sour cream. It's uh keto spiked cocoa. And I put that into the sour cream. And then I take one quarter of a cup of wild berries. And then I put a little bit of cinnamon. And then I put uh keto brains uh they call it coffee creamer, but I put it in that. And I stir it up. And then it becomes like this is what I eat every night, right? And then I put some uh sometimes I put collagen powder in it too at night just to add like a little bit of protein. But that's like the last meal of the day typically like within two to three hours before I go to bed. But it's like you know it's it's a lot of calories but it's also a little bit light. It's not I don't eat my our dinner we eat real early around like 4: 00 or 5 and then you know I'll have that around 8 or 9 or something. Go to bed at like 11. Yeah, I I really love that you're kind of busting the myth that ketogenic diet or being in a state of ketosis only requires to eat highfat animal foods day in day out that you can actually incorporate a little bit of carbohydrate. You can definitely eat fruits and berries and polyphenols and things like that and still maintain the state of ketosis and also utilize exoggenos ketones for example in a form of MCT or C8 oil uh to do that as well. Um to be mindful of your time I think we have time for one more question. Would it be okay? Sure. I would love to cover your supplements and also what do you think are the best supplements to take for brain energy and energy levels and mental performance? Yeah, I think the ones that I mentioned ones that I use staple are keto start by Audacious Nutrition. So that's the DL beta hydroxybutyrate uh delivers about uh 6 to 10 grams of BHB. Now sometimes like it'll list on the product will say it'll have this amount of exog ketones but this is sort of standardized to the
but this is sort of standardized to the actual BHB so the salt. So it's like that amount of BHB minus the electrolytes. Uh I like that I like magnesium uh glycinate or glycine. Magnesium glycinate is something that I have been using. I take it a little bit later in the day too. I take it like after lunch like mid to later part of the day. Uh glycine can have sort of like a calming effect as does magnesium too and I think glycine has some interesting properties. So MCT DL beta hydroxybutyrate magnesium glycinate magnesium 3enate too which crosses the blood brain barrier. Uh I use that situationally. I have a bottle of it and we'll use it, you know, periodically for uh if I just feel like I need to calm down a little bit or just, you know, under stress and I uh but I typically I I've been using that for for some time. Uh creatine creatine monohydrate is something that I've used typically about 10 to 15 grams per day. I even give that to my dogs. I I feed my dogs, too. If we talk pet nutrition, fish, beef, eggs, and a little bit of broccoli and creatine. So, these are all things I get to my doll. Uh, so those uh vitamin D, I think I meant and DHEA. So, consistently, my blood work shows DHEA in normal range, but low to normal range. So, I do about 25 milligrams, I think, uh, of DHEA, maybe 50 milligrams per day, uh, in the morning, first thing in the morning. And that shoots me up a little bit over if I get my test, but later in the day it's like within that optimal normal range. Uh melatonin, not sure if I mentioned that, but melatonin is something that I've used pretty much continuously since probably the mid 90s. Melatonin and uh occasionally. What What do melatonin do you use? Yeah, I I buy the like the little chewable ones and I they're 10 milligrams, but I break them into quarters. So I break one and half them break. So, typically about 2. 5
break. So, typically about 2. 5 milligrams of melatonin. I will chew it, hold it underneath my tongue about an hour before bed, and I think that does help a little bit with uh sleep latency. That said, I've sort of run out of melatonin. I've done that occasionally and I don't really notice any difference like in my uh sleep score or anything like that. Uh although I think melatonin has a lot of other benefits to it. So uh I mean I take it in the evening but I did research on melatonin on hippocample brain slice preparation. So uh you can take the brain out of an animal and look and slice it like a piece of bread and then measure it oxidative stress under different graded levels of oxygen. And in those those experiments uh I tested the effects of melatonin on superoxide production and I published that in the journal of neurohysiology back about 20 years ago. And uh so I've always been interested in melatonin and um and even the military was interested as in it as a neuroprotective agent but they did not utilize it because the the potential sedating effects of it. So melatonin is something that I've used um and you know if I feel like I have a cold coming on or something like that I do uh an acetylcyine acetylcyine NAD vitamin C and ginsing. So I keep that sort of separate and if I travel or if I feel like I could be exposed to someone that was sick or maybe my immune system is challenged uh I will do like you know two to one to two grams of uh NN NN uh NAD so the NAD precursor and I'll take an acetylcyine and then jins singh my wife has always used that situationally and then vitamin C too uh I'll use for you know if I feel like I'm getting a cold they're coming down with something to boost, you know, immune function. But I think that's it. And, you know, I use about like the five or six things, but I don't really do anything beyond that. Just the exogenous ketones, MCT, vitamin D, creatine, DHEA,
ketones, MCT, vitamin D, creatine, DHEA, melatonin. Uh these are things that are like in my cabinet that I take every day. And then the other things I I'll use situationally. I I love that stuff. So today I've taken uh metal folate, elanine, magnesium elriionate, vitamin D and K, creatin and collagen. And in the evening I usually take glycine, melatonin, NAC and oh I also took aantine and omega3 but that's very very similar to yours actually. Yeah, aanthin too. Yeah, I actually I teach redux biochemistry and aazanthin is something that I teach about. Uh, it gives the flamingos that we have here in Florida that pink color because they eat the shrimp and the shrimp well the shrimp get it from the algae and then they it's in the shrimp makes the shrimp pink and then the flamingos eat the shrimp and it makes them pink and I it's in part of my uh my lecture course that I when I talk about aan aazanthin yeah I don't take I think my wife may take that but yeah yeah that's a good one I had a PhD student that did her uh dissertation uh on asanthin it had some interesting properties So as to something I take it primarily for sun protection. Uh I had a discussion with Dr. Alexis Ortega who is specialized to aesthetic longevity medicine and longevity medicine in general but one of the big areas that he does is like aesthetic and he he uses nutritional approaches, supplements, detox etc. And um he told I think it was one of his favorites for the fact that the high loads of carotenoid in a santin per se can actually travel to the skin and it acts sort of as an internal sun sunscreen as well. So especially in the summer I really like it or when I travel to some sunny countries. Well thank you so much. This has been extremely interesting. I I think I still have some question left but maybe next time. Let's um let's do not four years
time. Let's um let's do not four years from now but hopefully I can get you back sometime. Yeah. And uh thank thank you so much. Do you have any any final words you would like to say or anything about ketones or uh no I think you know I direct people to I have an information website so ketoonutrition. org or and then we have uh so I do host a podcast called the metabolic link podcast and that's part of the metabolic health initiative and the metabolic health initiative is an ACCME accredited medical education platform that practitioners can uh get on that platform and there's various things like on female you know hormone optimization male male health there's nutrition there's things about you know ketogenic nutrition ketone metabolic therapies. Uh we had Andy Galpin on I think he did a course. Kyle Gillette did did like an overview of like you know health optimization. So we have different modules on the uh the the metabolic health initiative platform that if you want to get CME credits and things like that but yeah the metabolic link podcast, keto nutrition. org and metabolic health initiative are things that you know like people to to know about. They can learn more if they want to learn about my research. You can go to PubMed and just put in, you know, my name, Dagastino, DP initials, and should come up, you know, about 100 reviews and things like that on different topics we discussed. And Metabolic Link podcast can be found on YouTube as well. Yeah, YouTube, I think, you on Spotify, Apple podcast, things like that. So, perfect. Thank you so much, Dr. Dakos. My pleasure. Thanks for having me.
Transcript auto-generated by YouTube. Verbatim — duplicates intentionally preserved.
Ketones are not simply an alternative calorie source. They act as signaling molecules, influencing inflammation, oxidative stress, mitochondrial function, and the balance between glucose and fat metabolism.
In plain language, the body can shift into a steadier energy pattern when ketones rise and glucose pressure falls. The felt experience may be clearer focus, fewer energy swings, and a stronger sense of metabolic control.
D'Agostino returns often to neuroprotection and brain energy stability. The brain is metabolically demanding. When fuel delivery becomes unstable, attention, mood, and resilience can suffer.
Ketones may help by giving neurons a clean, efficient substrate while also affecting the signaling environment around inflammation and oxidative stress. This is why therapeutic ketosis is being studied in epilepsy, neurodegenerative disease, psychiatric conditions, and high-stress performance.
Ketones are fuel, but they are also information. — Contrast Collective
The conversation distinguishes nutritional ketosis from therapeutic ketosis. A gentle ketogenic pattern for energy and body composition is not the same as using ketosis as a clinical strategy.
That distinction matters. Glucose, ketones, insulin, protein, body composition, training, sleep, and medical history all shape whether ketosis is useful, neutral, or poorly matched. Precision matters more than intensity.
The glucose-ketone index gives clinicians and researchers a way to understand the relationship between circulating glucose and ketones. In cancer metabolism and neurological work, that relationship can be more informative than either number alone.
For everyday health, the principle is simpler: metabolic flexibility depends on the ability to move between fuels. A resilient body can use glucose when it is appropriate, fat when it is appropriate, and ketones when conditions call for them.
D'Agostino also discusses hyperbaric oxygen therapy and its potential intersection with ketones. Oxygen pressure and metabolic fuel both change the cellular environment.
This is not a casual wellness stack. It is a reminder that physiology responds to layered signals. Heat, cold, breath, oxygen, fasting, nutrition, sleep, and movement all ask the body to adapt. The art is choosing the right signal at the right time.
The longevity lesson is not that everyone should chase high ketone numbers. It is that fuel choices shape biology over time.
Ketosis can be a useful protocol for some people. For others, the better path may be protein adequacy, resistance training, time-restricted eating, improved sleep, or better glucose control without strict carbohydrate restriction. The goal is not identity. The goal is metabolic clarity.
Metabolic health is built by matching the signal to the person.
Use ketone testing as feedback, not as a scorecard.
Protect protein, minerals, sleep, and resistance training when experimenting with carbohydrate restriction.
Work with a qualified clinician before using ketogenic protocols for neurological, psychiatric, cancer, or complex medical concerns.
